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| Intensive Care Med, 2003 Dec, 29(12), 2170 - 3 Epub 2003 Sep 12. Impact of adequacy of initial antimicrobial therapy on the prognosis of patients with ventilator-associated pneumonia; Leroy O et al.; OBJECTIVE: To study the prognostic impact of the appropriateness of initial antimicrobial therapy in patients suffering from ventilator-associated pneumonia (VAP) . DESIGN AND SETTING: Observational cohort from January 1994 to December 2001 in one intensive care unit (ICU) from an university-affiliated, urban teaching hospital . PATIENTS: All 132 consecutive patients exhibiting bacteriologically documented VAP during ICU stay . MEASUREMENTS AND RESULTS: Initial antimicrobial treatment was deemed appropriate when the period from initial VAP diagnosis and subsequent administration of antibiotics was within 24 h and all causative pathogens were in vitro susceptible to at least one of the antibiotics of the regimen . Such a treatment was present in 106 episodes . Fifty-eight patients died . In bivariate analysis an appropriate initial antimicrobial therapy was associated with a significantly lower mortality rate (40% vs . 62%) . In multivariate analysis the three independent factors present upon VAP onset and associated with death were pulmonary involvement of more than a single lobe on chest radiograph, platelet count less than 150000/mm(3), and Simplified Acute Physiology Score II higher than 37 . Appropriate antimicrobial therapy was associated with a nonsignificant trend toward a lower mortality . CONCLUSIONS: In our cohort the mortality rate was lower in patients suffering from VAP when the initial antimicrobial therapy was appropriate . However, such a factor did not appear as an independent prognostic factor. Nephrol Dial Transplant, 2003 Oct, 18(10), 2067 - 73 The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing; Anding K et al.; BACKGROUND: Neutrophil functions in haemodialysis (HD) patients are altered by uraemia and by HD procedure . We investigated details of the neutrophil dysfunction as its nature and origin is not well understood . This is reflected by conflicting results about neutrophil phagocytosis activity and by scarce data on the neutrophil killing capability in HD patients . METHODS: Using a flow-cytometric test system we have measured simultaneously phagocytosis and the production of reactive oxygen species (ROS) of neutrophils and in parallel antimicrobial killing of yeast by neutrophils . 117 whole-blood samples of healthy controls and 50 pre- and 50 post-dialysis samples of HD patients, half of them with diabetes mellitus (DM), have been evaluated . We have constructed a model to account for the dependence on the stimulus-to-cell ratio and obtain means for phagocytosis and killing at different incubation times . RESULTS: (i) HD patients have significantly lower neutrophil killing (20%) than healthy controls . (ii) Dialysis improves the killing capability by 10-15%, after dialysis the killing activity remains significantly (10%) below that of the controls . (iii) The percentage of neutrophils, which exhibit phagocytosis and produce ROS, does not differ significantly between HD patients and healthy controls . (iv) Age has no significant influence on phagocytosis and killing . CONCLUSION: The neutrophil killing capability is reduced in HD patients while the amount of neutrophils that phagocyte and produce ROS remains unchanged . Functional impairment of uraemic neutrophils is therefore mainly a result of their reduced capability to kill microorganisms intracellularly. J Biol Chem, 2003 Nov 28, 278(48), 48485 - 90 Epub 2003 Sep 17. The RuvAB branch migration complex can displace topoisomerase IV.quinolone.DNA ternary complexes; Shea ME et al.; Quinolone antimicrobial drugs target both DNA gyrase and topoisomerase IV (Topo IV) and convert these essential enzymes into cellular poisons . Topoisomerase poisoning results in the inhibition of DNA replication and the generation of double-strand breaks . Double-strand breaks are repaired by homologous recombination . Here, we have investigated the interaction between the RuvAB branch migration complex and the Topo IV.quinolone.DNA ternary complex . A strand-displacement assay is employed to assess the helicase activity of the RuvAB complex in vitro . RuvAB-catalyzed strand displacement requires both RuvA and RuvB proteins, and it is stimulated by a 3'-non-hybridized tail . Interestingly, Topo IV.quinolone.DNA ternary complexes do not inhibit the translocation of the RuvAB complex . In fact, Topo IV.quinolone.DNA ternary complexes are reversed and displaced from the DNA upon their collisions with the RuvAB complex . These results suggest that the RuvAB branch migration complex can actively remove quinolone-induced covalent topoisomerase.DNA complexes from DNA and complete the homologous recombination process in vivo. Ann Intern Med, 2003 Sep 16, 139(6), 463 - 9 The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections; McMahon BJ et al.; BACKGROUND: The relationship between previous antimicrobial treatments and infection with drug-resistant Helicobacter pylori is unknown . OBJECTIVES: To determine whether previous use of antimicrobial agents predicts subsequent antibiotic resistance of H . pylori and whether resistance affects treatment outcome . DESIGN: Retrospective cohort analysis of adults recruited sequentially from a clinical practice . SETTING: A referral hospital in Anchorage, Alaska . PATIENTS: 125 adults infected with H . pylori . MEASUREMENTS: Medical records were reviewed for antimicrobial agents prescribed in the 10 years before diagnosis with H . pylori infection . Antimicrobial susceptibility of H . pylori isolates obtained from endoscopic gastric biopsy was determined by using agar dilution . Cure was determined by using the urea breath test 2 months after antimicrobial treatment . RESULTS: Among the 125 patients, 37 (30%) were found to have H . pylori isolates resistant to clarithromycin and 83 (66%) were found to have H . pylori isolates resistant to metronidazole . Resistance to clarithromycin was associated with previous use of any macrolide antibiotic (P < 0.001), and resistance to metronidazole was associated with previous use of metronidazole (P < 0.001) . The odds of isolates being resistant to clarithromycin increased in relation to the number of courses of macrolides received (P < 0.001) . Among 53 persons treated with clarithromycin-based regimens, treatment failed in 77% of those carrying clarithromycin-resistant H . pylori (10 of 13) and 13% of those with clarithromycin-susceptible strains (5 of 40) (relative risk, 6.2 {95% CI, 1.9 to 37.1}; P < 0.001) . CONCLUSIONS: Previous use of macrolides and metronidazole is associated with H . pylori resistant to these antimicrobial agents . Clarithromycin resistance is associated with a greater risk for failure with clarithromycin-based treatments. Life Sci, 2003 Oct 10, 73(21), 2675 - 85 Effects of moxifloxacin in zymogen A or S . aureus stimulated human THP-1 monocytes on the inflammatory process and the spread of infection; Hall IH et al.; Antimicrobial agents have been reported to exhibit immunomodulatory and anti-inflammatory activities, both in vivo and in vitro (e.g., in human lymphocytes, macrophages and monocytes) . The effects of moxifloxacin on cytokine immunomodulatory mediators, free radical generation and hydrolytic enzyme activities in zymogen A-stimulated human THP-1 monocytes were evaluated . An increase in c-AMP levels, protein kinase C activity, and the release of nitric oxide and hydrogen peroxide with a decrease in pH occurred within the first hour . Further, the effects of moxifloxacin were reduced by agents which blocked the oxygen burst, lysosome-phagosome fusion, and the energy generation within the cell . After 4 h, there was a decrease in NAG and cathepsin D activities, lipid peroxidation and the release of pro-inflammatory cytokines . These data indicate that moxifloxacin may modify the acute-phase inflammatory responses through inhibition of cytokine release in monocytes . Moxifloxacin inhibited the release of TNFalpha, IL-1, IL-6, and IL-8 in a concentration-dependent manner across a range of 0.004 to 4 microg/mL . After 4 h, there was a decrease in the release of these cytokines, thus interfering with the inflammation process to reduce infection and its spread . The effects of moxifloxacin appear initially to activate monocytes to kill bacteria through the innate immune process by releasing ROS and lysosomal hydrolytic enzymes as well as phagocytosis of the organism . At a later time the bacteria are killed through a Bacterialstatic mechanism of protein synthesis inhibition and there is a reversal of the effects of moxifloxacin on cytokine release, free radical generation and hydrolytic enzymes so that lipid peroxidation and tissue destruction by the infection process is suppressed. Farmaco, 2003 Sep, 58(9), 951 - 9 An investigation of the biological effect of structural modifications of isothiosemicarbazones and their cyclic analogues; Maccioni E et al.; Several arylideneisothiosemicarbazones and arylidenehydrazothiazoles have been synthesised to obtain new antimicrobial agents . Their activity against both bacteria and fungi has been tested and some interesting informations about their biological activity have been obtained. Farmaco, 2003 Sep, 58(9), 875 - 81 Synthesis, X-ray crystal structure and biological properties of acetylenic flavone derivatives; Artali R et al.; The reactions of iodoflavone with 3-methyl-3-hydroxybut-1-yne and 3-methylbut-3-en-2-yne are described and the antimicrobial and cytotoxic activities of the obtained compounds have been tested . The molecular structures of 6-(3-hydroxy-3-methylbut-1-ynyl)-flavone (1a) and 6-(3-methylbut-3-en-1-ynyl) flavone (1b) have been determined by X-ray crystallography . The planar configuration of the two compounds has been attributed to intramolecular hydrogen bond interactions . In 1a, the presence of the hydroxyl group determines a dimeric arrangement of the molecules . In both compounds in the crystal state, molecular stacking has been observed. Farmaco, 2003 Sep, 58(9), 639 - 50 Quinoxaline chemistry . Part 16 . 4-substituted anilino and 4-substituted phenoxymethyl pyrrolo{1,2-a}quinoxalines and N-{4-(pyrrolo{1,2-a}quinoxalin-4-yl)amino and hydroxymethyl}benzoyl glutamates . Synthesis and evaluation of in vitro biological activity; Alleca S et al.; Twenty eight pyrrolo{1,2-a}quinoxalines bearing at position 4 various substituents related to the moieties present in classical and non classical antifolic agents were prepared and evaluated in vitro for antiproliferative activity . In an in vitro screening performed at NCI, several compounds emerged as potent antiproliferative agents at concentrations ranging between 10 and 100 microM . Interestingly, some of these compounds proved active also against bovine and murine DHFR (Farmaco 53 (1998) 480) . More recently, a compound of classical antifolate type has been reported to be a potent inhibitor of hDHFR in vitro (Farmaco 58 (2003) 51) . We then synthesized new derivatives that, in our hands, were endowed with in vitro antiproliferative activities as low as 3.4 microM against a panel of cell lines derived from hematological and solid tumours . In addition, a complete screening of cytotoxicity, antiretroviral HIV-1 and antimicrobial activity has been carried out. Biochem Biophys Res Commun, 2003 Oct 3, 309(4), 879 - 84 Indolicidin, a 13-residue basic antimicrobial peptide rich in tryptophan and proline, interacts with Ca(2+)-calmodulin; Sitaram N et al.; Indolicidin, ILPWKWPWWPWRR-NH(2), a short 13-residue antimicrobial and cytolytic peptide characterized from bovine neutrophils, has the calmodulin-recognition 1-5-10 hydrophobic pattern (indicated by amino acids in bold), is cationic, and thereby fulfills the requirements to interact with calmodulin . Hence, we have investigated the calmodulin-binding properties of indolicidin . Indolicidin interacted with calmodulin with fairly high affinity in a Ca(2+)-dependent manner . However, when bound, the peptide did not adopt helical conformation . Indolicidin also inhibited calmodulin-stimulated phosphodiesterase activity with IC(50) values in the nanomolar range . Replacement of either the proline residues of indolicidin with alanines or tryptophan residues with phenylalanines did not affect binding to calmodulin . However, these replacements had distinctive effects on the conformations of the bound peptides . While the alanine analog of indolicidin adopted predominantly alpha-helical conformation, the phenylalanine analog remained largely unordered . Differences in the ability of these analogs to inhibit the calmodulin-stimulated phosphodiesterase activity were observed . While the alanine analog was capable of inhibiting the activity with IC(50) values comparable to that of indolicidin, the phenylalanine analog did not inhibit the activity . Our results indicate that ability to adopt amphiphilic alpha-helical structure is not a prerequisite for binding to calmodulin and also binding does not necessarily result in inhibition of calmodulin-stimulated enzyme activities. Int J Antimicrob Agents, 2003 Sep, 22(3), 205 - 10 Mobile genes coding for efflux-mediated antimicrobial resistance in Gram-positive and Gram-negative bacteria; Butaye P et al.; Efflux mechanisms that account for resistance to a variety of antimicrobial agents are commonly found in a wide range of bacteria . Two major groups of efflux systems are known, specific exporters and transporters conferring multidrug resistance (MDR) . The MDR systems are able to remove antimicrobials of different classes from the bacterial cell and occasionally play a role in the intrinsic resistance of some bacteria to certain antimicrobials . Their genes are commonly located on the bacterial chromosome . In contrast, the genes coding for specific efflux systems are often associated with mobile genetic elements which can easily be interchanged between bacteria . Specific efflux systems have mainly been identified with resistances to macrolides, lincosamides and/or streptogramins, tetracyclines, as well as chloramphenicol/florfenicol in Gram-positive and Gram-negative bacteria . In this review, we focus on the molecular biology of antimicrobial resistance mediated by specific efflux systems and highlight the association of the respective resistance genes with mobile genetic elements and their distribution across species and genus borders. Curr Infect Dis Rep, 2003 Oct, 5(5), 416 - 425 Bite Wound Infections; Myers JP; Patients with mammalian bite wounds account for hundreds of thousands of emergency department, urgent care center, and physician office visits in the United States each year . The types of wounds encountered by physicians range from insignificant scratches to life-threatening neck and facial injuries . Infectious complications of bite wounds are common, and the consequences of these infections are significant and sometimes disabling . This article reviews the infectious complications of cat, dog, and human bite wounds . The prevention of tetanus and rabies virus infection, the appropriate antimicrobial treatment of bacterial infections, and the frequent need for surgical consultation and intervention are emphasized. J Med Chem, 2003 Sep 25, 46(20), 4240 - 3 Oxidosqualene cyclase inhibitors as antimicrobial agents; Hinshaw JC et al.; Small-molecule oxidosqualene cyclase (OSC) inhibitors were found to be effective in assays against cloned OSC-like enzymes from human pathogens . A combinatorial library was prepared and used to identify lead compounds that inhibit the growth of Trypanosoma cruzi, Leishmania mexicana amazonensis, and Pneumocystis carinii in culture . Selectivity for the microorganisms in preference to mammalian cells was observed. Wien Med Wochenschr, 2003, 153(15-16), 349 - 53 {From pneumonic infiltration to parapneumonic effusion--from effusion to pleural empyema: internal medicine aspects of parapneumonic effusion development and pleural empyema}; Domej W et al.; Infectious processes cause the majority part of all clinically relevant pleural effusions which frequently complicate the course of pneumonia . The assessment of an inflammatory effusion requires a careful history, physical examination, imaging techniques and clinical workup . The presence of polymorphonuclear leukocytes, high LDH-activity (> 200 U/L) and protein level (> 3 g/dL) in a pleural effusion indicates acute inflammation . An effusion is usually called empyema, when large numbers of neutrophils form thick, turbid exudates within preexisting body cavities . A thoracic empyema may occur as a result of primary or secondary pleural pathologies and in most cases involves infection with bacteria, frequently provided by progressing pneumonia . There are several therapeutic options for treatment of parapneumonic effusions and of thoracic empyemata, respectively . Optimal therapeutic management and antimicrobial medication to the infected pleural space depend in part on the stage of the empyema at presentation . Treatment can vary from a conservative medical approach in uncomplicated or small parapneumonic effusions to invasive surgical interventions in fibroprulent or organizational stages of empyema . Empyemata usually progress from a parapneumonic exudative stage (stage I), when the fluid is still sterile, with low leukocyte counts, low LDH, physiological pH, and normal glucose, to the fibropurulent {figures: see text} stage (stage II) with high leukocyte counts, high LDH activity, low pH, and low glucose, and finally to the organizational stage (stage III), in which fibroblasts convert fibrin strands into inelastic membranes . Pleural peels and pockets may compartmentalize the viscous empyematous fluid and can cause serious restrictive ventilatory impairment . Each patient must be individually evaluated to determine the nature of the exudate and the stage of the pleural space infection . Due to its high mortality rate (5%) a thoracic empyema requires prompt treatment . Diagnostic thoracentesis and withdrawal of liquid for the microbiological, cytological and biochemical analysis is urgently recommended in all cases to assess severity of the disease and the likelihood of a complicated or uncomplicated course, and to select the most appropriate treatment option. Wien Med Wochenschr, 2003, 153(15-16), 345 - 8 {Are new antibiotics in therapy of respiratory tract infections necessary?}; Haberl R et al.; Increasing worldwide antibacterial resistance among respiratory pathogens, especially S . pneumoniae, are an emerging problem in the treatment of respiratory tract infections . In some areas penicillin-resistant S . pneumoniae increased to 80% and macrolide-resistance and MLSb-resistance are an evolving problem . In addition, increasing resistance to quinolones has been documented in Hong Kong and in Spain . One way to combat increasing resistance is the development of new antimicrobial drugs . However, the practice of just changing one drug for another without also altering poor prescribing habits merely results in different resistance issues . In the long-term, to prevent increasing resistance, clinicians must be aware of restrictive antibiotic prescription and adequate dosages. Wien Med Wochenschr, 2003, 153(15-16), 342 - 4 {Pharmacokinetics of antibiotics in inflamed and healthy lung tissue}; Tomaselli F et al.; The pharmacokinetic profile of antibiotics at the site of antiinfective action is one of the most important determinants of drug response, since it correlates the antimicrobial effect . Up to now, only limited information on the lung tissue pharmacokinetics of antibiotic agents has been available . The aim of in-vivo microdialysis is to measure antibiotic penetration into the extracellular space fluid of normal or pneumonic human lung parenchyma . The lung penetration of cefpirom in elective thoracic surgery and piperacillin in septic thoracic surgery, substances with low protein binding, was measured . Intra-, or postoperatively, respectively, microdialysis probes were inserted into normal or pneumonic lung tissue and into healthy skeletal muscle to obtain reference values . Serum and microdialysis samples were collected at 20-minute intervals for at last 8 hours . The intrapulmonary concentrations of the antibiotics exceeded the minimum inhibitory concentrations (MIC) for most relevant bacteria for 4-6 hours . The procedure was well tolerated by all patients and no adverse events or microdialysis-associated side effects were observed . This microdialysis technique enabled continuous tissue pharmacokinetic measurement of free, unbound anti-infective agents in the lung tissue, even in pneumonia. Arzneimittelforschung, 2003, 53(8), 590 - 9 Antimicrobial activity of N-acylphenothiazines and their influence on lipid model membranes and erythrocyte membranes; Motohashi N et al.; The antibacterial activity and influence on lipid model membranes and erythrocyte membranes of 24 N-acylphenothiazines and trifluoperazine were studied . (1) Among 24 phenothiazines, the antimicrobial activity of amino maleates was the highest . (2) The influence of phenothiazines on model liposome and erythrocyte membranes was studied using N-phenyl-1-naphthylamine (NPN) as fluorescence probe . From the three types of phenothiazine substitution (H, Cl, CF3) at position 2, CF3-phenothiazines were the most effective in the interaction with liposomal membranes . (3) As measured by the polarization degree of 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence, the alteration of membrane fluidity induced by CF3-phenothiazines was the biggest . Surprisingly, phenothiazines induced stomatocytic shape alterations (invaginations) in erythrocytes and at higher concentrations, also hemolysis of erythrocytes was observed . (4) The microcalorimetic measurements of influence of phenothiazines on thermal behaviour of synthetic lipid systems confirmed the previously obtained results . The main transition temperature and enthalpy of transition of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were significantly modified by CF3-phenothiazines, suggesting their penetration of the lipid bilayer . Above results show that phenothiazine maleates were generally more effective than other phenothiazines used in this study. Antibiot Khimioter, 2003, 48(4), 27 - 34 {Efficacy of various antimicrobial agents in the treatment of epidemic typhoid fever}; Makhnev MV; During superepidemic of a typhoid fever in Tadjikistan the efficiency of application in clinics and of 14 antimicrobial agents representing almost all basic chemical classes was investigated . Remarkable variation of frequency and type of S . typhi resistance to these preparations up to epidemic and especially in its process was demonstrated . The absence of absolute (100%) efficacy of the investigated agents in vivo and in vitro was shown . The reasons of low efficacy of etiotropic treatment of the patients with typhoid fever are analysed. Bone Marrow Transplant, 2003 Oct, 32(7), 709 - 14 Nontuberculous mycobacterial infections in Chinese hematopoietic stem cell transplantation recipients; Au WY et al.; Between 1995 and 2002, nine cases of nontuberculous mycobacterium (NTM) were isolated from 462 allogeneic stem cell transplant (SCT) recipients (1.9%), and none from 139 autologous cases . They included three cases each of Mycobacterium fortuitum and M . chelonae, and single cases of M . scrofalaceum, M . gordonnae and M . avium complex . Seven cases were respiratory, including five cases requiring treatment, and two involved infected catheters and vascular conduits . Compared with nine cases of mycobacterium tuberculosis (MTB) isolated in the same period, NTM isolation occurred later after HSCT and involved more unrelated donors . Important risk factors for NTM infection included significant aGVHD (P=0.043), leukemia relapse (P=0.022), MUD and mismatch SCT (P<0.001) and existence of BO (P<0.001) . Coinfection with aspergillus was common . Invasive NTM disease required prolonged antimicrobial treatment in five cases due to M . fortuitum and M . chelonae . With better MTB prophylaxis, intensive immunosuppression and better awareness, NTM has become an emerging threat in oriental allogeneic HSCT recipients . The cutoff between colonization and infection, and the threshold for starting treatment is unclear . NTM isolation is a marker for severe immunosuppression and poor prognosis . When there is doubt over species identity or extent of infection, broad-spectrum cover may be prudent. APMIS, 2003 Jul-Aug, 111(7-8), 715 - 24 Dendritic cells as inducers of antimicrobial immunity in vivo; Sundquist M et al.; Models of infection have provided important insight into the function of dendritic cells (DC) in vivo . Several microbial products induce DC maturation via Toll-like receptors, a process that is crucial for the ability of DC to initiate adaptive immune responses . Splenic DC have also been shown to produce IL-12 during infection in vivo . This DC-derived IL-12 might be important to skew T cell responses towards Th1 . Microbial infections also induce changes in the DC populations of lymphoid organs, often in a subset-specific manner, manifested as an accumulation and redistribution of DC . Furthermore, data are emerging pointing at an absolute requirement of DC in priming of naive T cells in vivo. Oral Dis, 2003, 9 Suppl 1, 63 - 70 Use of antimicrobial agents during supportive periodontal therapy; Venezia E et al.; Individual susceptibility to periodontal breakdown involves an interplay of genes, periodontal pathogens and other modulating factors . Anti-infective treatment, which includes oral hygiene measures, mechanical debridement, pharmacologic intervention and surgery, has been shown to be effective in arresting the progression of periodontal disease . Nevertheless, due to the chronic nature of the disease, susceptible individuals who are not maintained in a supervised recall program subsequent to the active treatment phase, show signs of recurrent destruction . Supportive periodontal therapy (SPT) is an integral part of periodontal treatment for patients with history of periodontitis, and is needed to prevent recurrence of disease in susceptible individuals . To prevent re-infection with periodontal pathogens, SPT includes elimination of dental plaque and bacteria from the oral cavity, thereby preventing the recurrence of pathogens into the gingival area . For individuals at risk of developing periodontitis, SPT should combine self-performed and professional anti-infective therapy, using mechanical and pharmacological means . The existing evidence suggests that the adjunctive use of antimicrobial pharmacologic therapy during SPT may enhance the results of mechanical debridement . The use of antimicrobials varies between patients, and is dependent on risk assessment and longitudinal monitoring of the clinical status of the periodontium. Oral Dis, 2003, 9 Suppl 1, 45 - 50 Locally delivered antimicrobials for the treatment of chronic periodontitis; Etienne D; The basic treatment of chronic periodontitis is a mechanical debridement of periodontal pockets by scaling and root planing (S/RP) in combination with efficient plaque control . Locally delivered antiseptics (LDA) have been proposed to practitioners and, while subgingival irrigation of antiseptics is still used in clinical practice, the introduction in our therapy of a slow release and sub-gingival delivery of tetracycline has changed the rationale from a mechanical treatment towards a combined therapy for full mouth/sites disinfection . Various antibiotics, antiseptics and resorbable carriers are now proposed with similar targets to arrest disease progression . In chronic periodontitis, LDA cannot be used routinely in combination with S/RP, because of the limited clinical benefit, even if an increased percentage of deep sites may show an improvement . Prospective multicenter studies considering risk factors for disease progression have to be designed to identify patients who may benefit the most from LDA . For non-responding sites or recurrent pockets, the controversies are limited, because a combined S/RP and LDA may avoid the need for surgery . However, the patient cost/benefit ratio needs to be estimated as well as adverse effects in particular antibiotics. Oral Dis, 2003, 9 Suppl 1, 38 - 44 Systemic antimicrobials in the treatment of chronic periodontal diseases: a dilemma; Addy M et al.; The use of systemic antimicrobials in the treatment of acute and chronic periodontal diseases must be viewed as a dilemma . On the one hand, the approach is attractive because of the microbial nature of periodontal diseases but, on the other hand, evidence of benefit of these agents is equivocal for the majority of periodontal diseases and antimicrobials have the potential to cause harm . The disadvantages of systemic antimicrobials can be grouped under the headings of allergic reactions, superinfection, toxicity, drug interactions, patient compliance and, perhaps of most widespread importance, bacterial resistance . Mechanical debridement methods, including drainage of pus for acute periodontal abscesses, should be considered the first line treatment for most periodontal diseases . Systemic antimicrobials should be considered as adjuncts to mechanical debridement methods and, in chronic disease, never used alone as they can predispose to abscess formation . Adjunctive systemic antimicrobials may be considered in acute disease where debridement or drainage of pus is difficult, where there is local spread or systemic upset . In chronic periodontal diseases, adjunctive antimicrobials should be considered in early onset or rapidly progressive disease or in advanced chronic adult disease where mechanical therapies have failed or surgery is not a preferred option . Inadequate oral hygiene and tobacco smoking are contraindications to the use of antimicrobials . The value of systemic antimicrobials, where other systemic risk factors co-exist, has still to be established . The role of microbial diagnosis and sensitivity testing for antimicrobial selection at this time must be questioned. Oral Dis, 2003, 9 Suppl 1, 30 - 7 Microbial shifts after subgingival debridement and formation of bacterial resistance when combined with local or systemic antimicrobials; Quirynen M et al.; Antibiotics have played a major role in the improvement of life expectancy in the last 50 years and have led many to believe that bacterial infections were about to vanish as a disease entity of any importance . Emerging problems resulting from a widespread use of antibiotics have modified the general perception of the capabilities of antimicrobial agents . Over the years, bacteria have become increasingly resistant to formerly potent antimicrobial agents, including some antiseptics . The use of antimicrobials may also disturb the delicate ecological equilibrium of the body, allowing the proliferation of resistant bacteria or non-bacterial micro-organisms . This shift may initiate new infections that are worse than the ones originally treated . No antimicrobial drug is absolutely non-toxic and the use of an agent carries accompanying risks . This paper discusses the development and occurrence of antimicrobial resistance in the subgingival flora towards antiseptics and local or systemic antibiotics and is focussed on the question: how can the outcome of periodontal therapy with/without antimicrobials be improved? Oral Dis, 2003, 9 Suppl 1, 11 - 5 Periodontal diseases: current and future indications for local antimicrobial therapy; Trombelli L et al.; The microbial etiology of gingivitis and periodontitis provides the rationale for use of adjunctive antimicrobial agents in the prevention and treatment of periodontal diseases . Although mechanical removal of supra- and subgingival calcified and non-calcified plaque deposits has been proved effective to control the gingival inflammatory lesions as well as to halt the progression of periodontal attachment loss, some patients may experience additional benefits from the use of systemic or topical antimicrobial agents . Such agents are able to significantly affect supra- and subgingival plaque accumulation and/or suppress or eradicate periodontal pathogenic microflora . Currently, properly selected local antiseptic and systemic antibiotic therapies can provide periodontal treatment that is generally effective, low-risk and affordable . This paper will briefly review the host-related conditions in which the periodontal preventive and therapeutic approaches may be effectively assisted by a local antimicrobial regimen . Potential future indications for adjunctive local antimicrobial therapy will also be discussed. J Huazhong Univ Sci Technolog Med Sci, 2003, 23(2), 203 - 5 Susceptibility of mixed infection of Ureaplasma Urealyticum and Mycoplasma Hominis to seven antimicrobial agents and comparison with that of Ureaplasma Urealyticum infection; Huang C et al.; In order to investigate the susceptibility of mixed infection of Ureaplasma Urealyticum (UU) and Mycoplasma Hominis (MH) to 7 kinds of antimicrobial agents and comparison with that of UU infection in NGU patients, the in vitro susceptibility was determined by using microdilution method . The positive results were analyzed . The results showed that the sequence of susceptibility to 7 kinds of antimicrobial agents for both UU infection group and UU-MH mixed infection group was almost the same from the highest susceptibility to the lowest accordingly: Josamycin, Doxycycline, Minocycline, Sparfloxacin, Roxithromycin, Ofloxacin and Azithromycin . The total drug resistance rate for UU-MH mixed infection group (97.67%) was significantly higher than that for UU infection group (44.67%, P < 0.01) . The highest drug resistance rate in UU group and UU-MH mixed infection group was 31.33% (Ofloxacin) and 90.48% (Azithromycin) respectively . UU-MH mixed infection showed an increased drug resistance and changes of drug resistance spectrum. Rev Esp Quimioter, 2003 Jun, 16(2), 172 - 87 {MDR efflux pumps and antimicrobial resistance}; Sanchez Diaz P; The term MDR (Multi Drug Resistance) system refers to a group of transporters which are able to expulse a wide range of quite different substrates . While this type of system was first described in eukaryotic cells in the late 1980s, the presence of MDR efflux-pumps in bacteria showing resistance to several drugs has been increasingly reported in the literature . Under laboratory conditions the expression of these MDR systems is usually down-regulated . On occasion, basal expression of these efflux pumps is allowed in wild type strains, thus suggesting a role of these MDR systems in the intrinsic of these microorganisms resistance to antibiotics . On the other hand, overexpression of these MDR efflux pumps, after induction or because of the emergence of mutations in their regulatory elements, is also important in acquired resistance to antibiotics . This review summarizes the most relevant features of the MDR systems described in bacteria, as well as the mechanisms that regulate their expression. Drugs Today (Barc), 1999 Feb, 35(2), 89 - 103 Antibiotics in inflammatory bowel disease; Chung PY et al.; The use of antibiotics as primary therapy in inflammatory bowel disease (IBD) has been an issue of great controversy among the experts in the field . Although the utility of certain antimicrobial agents in managing secondary complications, such as abscess formation, toxic megacolon and pouchitis, has been substantiated by clinical trials, clear evidence to support or undermine their use as primary therapeutic agents in IBD is lacking . This may be secondary to the fact that the etiology of IBD remains unknown, and, despite much speculation and research in the area, no infectious agent has been found to cause or contribute to the pathogenesis of these disorders . The dearth of data, in turn, has resulted in widely varying treatment strategies and a lack of a clear standard of care with regard to the use of antibiotics . (c) 1999 Prous Science . All rights reserved. EMBO Rep, 2003 Oct, 4(10), 976 - 81 Epub 2003 Sep 12. Directed expression of the HIV-1 accessory protein Vpu in Drosophila fat-body cells inhibits Toll-dependent immune responses; Leulier F et al.; Human immunodeficiency virus 1 (HIV-1) expresses several accessory proteins that manipulate various host-cell processes to achieve optimum replicative efficiency . One of them, viral protein U (Vpu), has been shown to interfere with the cellular degradation machinery through interaction with SCF(beta-TrCP) complexes . To learn more about Vpu function in vivo, we used the genetically tractable fruit fly, Drosophila melanogaster . Our results show that the directed expression of Vpu, but not the non-phosphorylated form, Vpu2/6, in fat-body cells affects Drosophila antimicrobial responses . In flies, the Toll and Imd pathways regulate antimicrobial-peptide gene expression . We show that Vpu specifically affects Toll pathway activation by inhibiting Cactus degradation . Given the conservation of the Toll/nuclear factor-kappa B (NF-kappa B) signalling pathways between flies and mammals, our results suggest a function for Vpu in the inhibition of host NF-kappa B-mediated innate immune defences and provide a powerful genetic approach for studying Vpu inhibition of NF-kappa B signalling in vivo. J Antimicrob Chemother, 2003 Oct, 52(4), 555 - 63 Epub 2003 Sep 12. How good is the evidence for the recommended empirical antimicrobial treatment of patients hospitalized because of community-acquired pneumonia? A systematic review; Oosterheert JJ et al.; BACKGROUND: For years, monotherapy with a beta-lactam antibiotic (penicillin, amoxicillin or second-generation cephalosporin) was recommended as empirical therapy for patients with community-acquired pneumonia (CAP) . A combination of a beta-lactam and a macrolide antibiotic was only recommended for patients with severe CAP needing intensive care treatment or when atypical pathogens, i.e . Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, were strongly suspected . However, new guidelines recommend a combination of a beta-lactam antibiotic plus a macrolide or monotherapy with a fluoroquinolone for all patients hospitalized with CAP . We evaluated whether treatment with a beta-lactam plus macrolide or quinolone monotherapy is truly superior to beta-lactam treatment alone . METHODS: We systematically reviewed available studies, retrieved from MEDLINE and by hand-searching reference lists from recent reviews and guidelines on the effectiveness of recommended empirical antimicrobial treatment of patients hospitalized because of CAP . RESULTS: Eight relevant studies were selected . In six studies significant reductions in mortality were found, in one study a reduction in hospital length of stay was found and in one study no beneficial effects could be demonstrated for treatment regimens with fluoroquinolone monotherapy or combinations of beta-lactams and macrolides . The beneficial value of macrolides or fluoroquinolones might be the result of a large and mainly unrecognized role of atypical pathogens in the aetiology of CAP, anti-inflammatory effects of macrolides or resistance to beta-lactams of the most important pathogens . However, the studies supporting the recommended treatment regimen were designed as non-experimental cohort studies . As a consequence, the results may have been influenced by confounding by indication . In addition, the outcomes showed several inconsistencies . CONCLUSIONS: A randomized controlled trial is warranted to circumvent the methodological flaws in the designs of the currently available studies . Since the addition of macrolides or treatment with fluoroquinolones may lead to enhanced antibiotic resistance, increased side effects and healthcare-related costs, such a fundamental change in the treatment of CAP should be based on valid data. Tuberculosis (Edinb), 2003, 83(5), 319 - 28 Role of Mycobacterium xenopi disease in patients with HIV infection at the time of highly active antiretroviral therapy (HAART) . Comparison with the pre-Haart period; Manfredi R et al.; BACKGROUND AND SETTING: A reliable and timely clinical, radiological, and bacteriological diagnosis, and an optimal treatment of non-tubercular mycobacteriosis (including Mycobacterium xenopi disease), remain an unanswered challenge for clinicians facing immunocompromised patients, including those with HIV infection . OBJECTIVE: The aim of our survey is to report the frequency, and the epidemiological, immunological, microbiological, clinical, and therapeutic features of all confirmed HIV-associated M . xenopi disease observed from 1993-2002, with special attention paid to eventual differences that emerged after the introduction of potent antiretroviral therapy (highly active antiretroviral therapy, HAART), on the basis of an international literature update . DESIGN AND RESULTS: Our series of 17 consecutive confirmed M . xenopi infections retrieved in 14 out of 3000 patients followed for HIV disease complications raises a broad series of clinical, diagnostic, therapeutic, and prophylactic concerns . The great majority of M . xenopi disease involved the lower respiratory tract, but atypical features including cavitation and prominent exudative features became apparent in patients successfully treated with HAART, pointing out the possible role of the so-called immune reconstitution syndrome in these episodes . CONCLUSIONS: Diagnostic problems represented by late or missed identification due to slow culture and frequently concomitant opportunistic disorders, join therapeutic difficulties due to the unpredictable in vitro antimicrobial susceptibility profile of these organisms, selection of treatment and chemoprophylaxis according with clinical-radiological and microbiological suspicion, and concomitantly administered medications. Southeast Asian J Trop Med Public Health, 2003 Mar, 34(1), 179 - 86 Utilization of restricted antibiotics in a university hospital in Thailand; Ayuthya SK et al.; Antibiotic resistance, a major negative consequence of antibiotic overuse, is an important problem worldwide . Various means have been used to control antibiotic usage including the use of an antibiotic order form (AOF), restricted antibiotic formularies and provision of educational information . The present study was designed to evaluate the use of antimicrobials in a 1,000-bed university hospital . Antimicrobial agents, likely to be abused namely ceftazidime, cefepime, cefoperazone/sulbactam, imipenem/cilastatin, meropenem, ciprofloxacin, netilmicin, vancomycin, azithromycin and clarithromycin, were selected for evaluation . A simple AOF with educational information was used as a mean to follow up the treatment . The investigator collected data from the filled AOF and the patient's charts of the Department of Internal Medicine from June to November 2000; all relevant data were assessed . The appropriateness of antibiotic use, assessed according to the criteria specified in the AOF, showed that 74% of these antibiotics were prescribed appropriately; this may prove the effectiveness of the system used in the present study . However, 348 of the 430 prescriptions (80.9%) were prescribed empirically at the initial stage for treatment of nosocomial infections in patients with serious conditions like pneumonia, sepsis and febrile neutropenia . Drugs that were frequently used empirically were ceftazidime (37.9%), imipenem/cilastatin or meropenem (19.3%), and cefoperazone/sulbactam (12.1%) respectively . Ceftazidime and imipenem/cilastatin or meropenem were also frequently used inappropriately among 111 prescriptions that were classified as an inappropriate prescribing . The most common misuses were prescriptions of the drug that did not follow the specified indications (70 prescriptions), no dosage adjustment in patients with renal impairment (39 prescriptions), improper dose (12 prescriptions) and improper dosing interval (9 prescriptions) . The results suggested overuse of certain antibiotics remain to be an unsolved problem . Better monitoring and strict controlled use of the problematic antibiotics, ie ceftazidime, imipenem/cilastatin or meropenem and vancomycin are essential to promote rational drug use as well as to reduce the frequency of drug resistance. N C Med J, 2003 Jul-Aug, 64(4), 148 - 56 Antibiotic prescriptions associated with outpatient visits for acute upper respiratory tract infections among adult Medicaid recipients in North Carolina; Brown DW et al.; BACKGROUND: North Carolina and the southeastern United States have the highest antimicrobial resistance rates for common respiratory tract pathogens in the nation . The excessive use of antibiotics for common outpatient infections is a major contributing factor in the emergence of antibiotic resistant bacteria . OBJECTIVE: To estimate the prevalence of oral antibiotic treatment for acute, nonbacterial respiratory tract infections among adult Medicaid recipients in North Carolina, and to describe a pilot project aimed at reducing the prevalence of oral antibiotic treatment among this population . METHODS: Using administrative claims data, we identified 24,137 Medicaid recipients, aged 18 to 64 years, who made at least one outpatient physician visit for acute nasopharyngitis (ICD-9, 460.x), acute pharyngitis (462.x), acute upper respiratory infection (465.9), acute bronchitis (466.0), or influenza (487.1) between October 1, 2000, and March 29, 2001 . We excluded adults with chronic bronchitis (ICD-9, 491.x), emphysema (492.x), asthma (493.x), or chronic obstructive pulmonary disease (496.x) . Pharmacy claims data were used to identify oral antibiotic treatment that occurred within 5 days of the outpatient visit . RESULTS: Overall, 63% (n = 15,189) of Medicaid recipients who made at least one outpatient visit during the observation period for one of the study conditions had a prescription filled for an oral antibiotic within 5 days . Residence in a rural county (64% vs . urban, 61%, p < 0.01) and in the eastern region of the state (65% vs . western region, 59%, p < 0.01) was associated with receipt of an antibiotic . Compared with the other principal study diagnoses, patients with acute bronchitis (44% of all outpatient visits) were 2.88 (95% CI = 2.72, 3.05) times more likely to receive oral antibiotic treatment after multivariate adjustment . SUMMARY: The prevalence of oral antibiotic treatment among adult Medicaid beneficiaries diagnosed with nonspecific upper respiratory infections, colds, pharyngitis, bronchitis, and influenza is high and varies significantly across patient demographics and geography . Interventions to reduce antibiotic prescribing are needed to reduce the progression of antimicrobial resistance. World Health Organ Tech Rep Ser, 2003, 918, i - vi, 1-59, back cover Evaluation of certain veterinary drug residues in food; Use of genetic profiling in leprosy to discriminate clinical forms of the disease; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USALeprosy presents as a clinical and immunological spectrum of disease . With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease . Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection . In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors . Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens. J Clin Endocrinol Metab, 2003 Sep, 88(9), 4426 - 31 Elafin in human endometrium: an antiprotease and antimicrobial molecule expressed during menstruation; King AE et al.; Elafin is an antiproteinase and antimicrobial molecule that is expressed at epithelial sites (for example, cervix) . This study details the expression and regulation of elafin in the human endometrium . Elafin mRNA and protein expression were examined in endometrium throughout the menstrual cycle and in first-trimester decidua . Real-time quantitative PCR showed that expression of elafin mRNA peaked during menstruation . Elafin protein was localized to leukocytes scattered in the endometrial stroma during the late secretory and menstrual phases . Faint immunostaining was also present in glandular epithelium at these cycle stages . Immunofluorescent colocalization of elafin with neutrophil elastase confirmed that elafin was expressed by endometrial neutrophils around the time of menstruation . This is consistent with the expression profile observed from immunohistochemical studies . Primary endometrial epithelial cells were treated with proinflammatory molecules, and elafin mRNA was studied . A combination of the proinflammatory mediators, IL-1 beta and TNFalpha, increased elafin mRNA levels by 4.6-fold . These results show that endometrium expresses elafin in a menstruation-dependent manner . This is attributable to the presence of infiltrating leukocytes and increased inflammatory signaling . Elafin will regulate proteolytic enzymes during menstruation and will contribute to the innate defense against uterine infection. Dev Comp Immunol, 2004 Feb, 28(2), 163 - 9 PR-39, a porcine antimicrobial peptide, inhibits apoptosis: involvement of caspase-3; Ramanathan B et al.; The porcine antimicrobial peptide, PR-39, has several activities beyond its function of killing bacteria . Here we report that PR-39 alters macrophage viability by inhibiting apoptosis, which was induced by nutrient depletion, LPS stimulation or camptothecin treatment . This antiapoptotic effect was pronounced resulting in significant reductions in annexin-V binding to externalized phosphatidylserine and was associated with a decrease in caspase-3 activity . These findings suggest that PR-39, a porcine neutrophil-derived antimicrobial peptide, might function in the inflammatory milieu not only to kill bacteria, but also to aid in modulating the viability of inflammatory cells by regulating apoptosis. Dev Comp Immunol, 2004 Feb, 28(2), 127 - 38 Isolation and characterisation of oncorhyncin II, a histone H1-derived antimicrobial peptide from skin secretions of rainbow trout, Oncorhynchus mykiss; Fernandes JM et al.; A potent antimicrobial peptide, tentatively named oncorhyncin II, was isolated from an acid extract of rainbow trout skin secretions . Amino acid sequencing showed that the first 17 residues of oncorhyncin II are identical to residues 138-154 of histone H1 from rainbow trout . Matrix-assisted laser desorption ionization mass spectrometry revealed that the purified peptide has a molecular mass of 7195.3Da . Taken together, these data indicate that oncorhyncin II is a 69-residue C-terminal fragment of histone H1, probably phosphorylated at two residues . Oncorhyncin II has minimal inhibitory concentrations in the submicromolar range against Gram-(+) as well as Gram-(-) bacteria and it does not display significant haemolytic activity towards trout erythrocytes . The purified peptide was found to induce a marked destabilisation of planar lipid bilayers without the formation of stable ion channels . Oncorhyncin II is possibly a cleavage product of histone H1 with a potentially important role in mucosal defence of rainbow trout. Dev Comp Immunol, 2004 Feb, 28(2), 89 - 95 Recognition of infectious non-self and activation of immune responses by peptidoglycan recognition protein (PGRP)-family members in Drosophila; Kurata S; Activation of the innate immune response involves recognition of the infectious non-self and subsequent activation of cellular and humoral reactions . Insect humoral reactions depend on primary and secondary responses . The primary response is mediated by the activation of cascades of constitutive proteins present in the hemolymph, such as the prophenoloxidase (proPO) cascade . The secondary response requires transcriptional activation of defense proteins, such as the induction of antimicrobial peptides . Drosophila possess specific mechanisms to discriminate between microbes and respond to infection by inducing the appropriate reactions . In innate immunity, pathogen-associated molecular patterns are recognized . The mechanisms for microbial recognition in Drosophila, however, are largely unknown . Recent data suggest that, in insect immunity, diverse peptidoglycan recognition protein members are involved in distinguishing between invading bacteria and activation of appropriate immune reactions. Parasite Immunol, 2003 May, 25(5), 259 - 70 Mucosal defences against Giardia; Eckmann L; Giardia lamblia (syn . G . duodenalis or G . intestinalis), the causative agent of giardiasis, is one of the most common causes worldwide of intestinal infections in humans . Symptomatic infection is characterized by diarrhoea, epigastric pain, nausea, vomiting, and weight loss, yet many infections are asymptomatic . The protozoan, unicellular parasite resides in the lumen and attaches to the epithelium and overlying mucus layers but does not invade the mucosa and causes little or no mucosal inflammation . Giardiasis is normally transient, indicating the existence of effective host defences, although re-infections can occur, which may be related to differences in infecting parasites and/or incomplete immune protection . Mucosal defences against Giardia must act in the small intestinal lumen in the absence of induction by classical inflammatory mediators . Secretory IgA antibodies have a central role in anti-giardial defence . B cell-independent mechanisms also exist and can contribute to eradication of the parasite, although their identity and physiological importance are poorly understood currently . Possible candidates are nitric oxide, antimicrobial peptides such as Paneth cell alpha-defensins, and lactoferrin . Elucidation of the key anti-giardial effector mechanisms will be important for selecting the best adjuvants in the rational development of vaccination strategies against Giardia. J Appl Microbiol, 2003, 95(4), 814 - 23 Patterns of antimicrobial activities from soil actinomycetes isolated under different conditions of pH and salinity; Basilio A et al.; AIMS: To evaluate the patterns of the production of antimicrobial compounds by diverse collection of actinomycetes isolated from different geographies under alternative conditions of pH and salinity in the media . METHODS AND RESULTS: Actinomycetes were grouped based on their method of isolation and their phenotype diversity was determined by total fatty acid analysis . A total of 335 representative isolates, including 235 Streptomyces species and 100 actinomycetes from other taxa, were screened for the production of antimicrobial activities against a panel of bacteria, filamentous fungi and yeasts, including some of clinical relevance . Production of antimicrobial activities was detected in 230 strains . In the case of the genus Streptomyces, 181 antimicrobial activities (77% of the tested isolates) were recorded . The activities observed among the other actinomycetes taxa were lower (49% of the tested isolates) . CONCLUSIONS: The results of this study support the idea that species of actinomycetes isolated in alternative selective conditions of pH and salinity present a significant capacity to produce compounds with antibacterial or antifungal activity . The best group of isolates in terms of production of active secondary metabolites was the one isolated in saline conditions . SIGNIFICANCE AND IMPACT OF THE STUDY: The results demonstrate that these actinomycetes strains isolated in alternative selective conditions of pH and salinity and collected from diverse geographical locations present a significant capacity to produce compounds with antibacterial or antifungal activity. J Appl Microbiol, 2003, 95(4), 734 - 43 A model for the efficacy of combined inhibitors; Lambert RJ et al.; AIMS: The method of the sum of the fractional inhibitory concentrations (SigmaFIC) is used ubiquitously in the investigation of antimicrobial combinations . The inherent assumption of this simple equation is that in a mixture all antimicrobials have identical dose responses . The aim of this work was to analyse the outcome of removing this assumption . METHODS AND RESULTS: A model to describe the efficacy of combined inhibitors was produced which removed the assumption of identical dose responses . The results of several checkerboard experiments showed that the new model, termed the facomb was a more general form of the SigmaFIC method, but the features described by the SigmaFIC as either synergy or antagonism could be attributed to differences in the dose responses of antimicrobials in combination . Where the model failed to adequately describe experimental data it was suggested that these might be cases of true antagonism or synergy . CONCLUSIONS: The SigmaFIC methodology used to describe the effect of antimicrobial combinations (preservatives and antibiotics) is valid only when it is demonstrated that individual components of the mixture have identical dose responses . Otherwise the SigmaFIC method is invalid . Descriptions of antimicrobial synergy may simply be due to the mixing of antimicrobials with differing dose responses . SIGNIFICANCE AND IMPACT OF THE STUDY: Studies aimed at producing synergistic mixtures of antimicrobials, which ignore the dose response of the individual antimicrobials, may waste valuable research effort looking for a physiological explanation for an apparent synergy, where none, in-fact, exists . Conversely, mixing antimicrobials with very different dose responses might lead to mixtures with an 'apparent' synergy which may themselves be very useful therapeutically. Biotechnol Bioeng, 2003 Nov 5, 84(3), 374 - 81 Inducible expression of green fluorescent protein in porcine tracheal epithelial cells by the bovine tracheal antimicrobial peptide promoter; Dyce PW et al.; Tracheal antimicrobial peptides (TAP) are expressed primarily in respiratory epithelial cells of cattle . The TAP expression is inducible upon challenge with bacteria and bacterial lipopolysaccharide (LPS) . In pigs, a promoter that can be activated by bacterial infection has yet to be identified . The objective of this study was to use green fluorescent protein (GFP) as a reporter gene to determine the function and inducibility of the bovine TAP promoter in porcine primary tracheal epithelial cells . Thus, evaluating the feasibility of using this promoter to direct transgene expression in porcine cells.The percentage of GFP expressing cells increased in response to LPS challenge in both a dose-dependent and time-dependent manner (p < 0.05) . Moreover, when the intensity of the GFP fluorescence was measured, it was observed that the percentage of cells that have a high intensity of GFP fluorescence, also increased gradually as LPS dose increased, the difference between the unchallenged (control) and challenged group become statistically significant at the concentration of 100 ng/mL after 36 h LPS challenge (p < 0.05) . The level of induced-expression driven by the TAP promoter was 67.8 +/-12.2% that of the cytomegalovirus (CMV) promoter . The intensity of GFP fluorescence by the TAP promoter was 39.8 +/- 7.6% when compared to the expression driven by the CMV promoter . These data suggest the TAP promoter functions at a lower, but comparable, level to the strong CMV promoter.Our data demonstrated that the bovine TAP promoter was functional in porcine primary tracheal epithelial cells . The ability of the TAP promoter to control gene expression in an inducible manner in the porcine respiratory tract presents an important application potential in transgenic animal studies . Arch Pharm Res, 2003 Aug, 26(8), 597 - 600 Gram-positive bacteria specific properties of silybin derived from Silybum marianum; Lee DG et al.; Silybin has a potent antibacterial activity, more potent than silymarin II, against gram-positive bacteria without hemolytic activity, whereas it has no antimicrobial activity against gram-negative bacteria or fungi . The mode of action of silybin against the gram-positive bacterial cell was examined by investigating the change in plasma membrane dynamics of bacterial cells using 1,6-diphenyl-1,3,5-hextriene (DPH) as a membrane probe and by assessing the inhibition of macromolecular synthesis using radiolabeled incorporation assay . The results showed that silybin inhibited RNA and protein synthesis on gram-positive bacteria. Pharmazie, 2003 Aug, 58(8), 587 - 9 Constituents of Peucedanum zenkeri seeds and their antimicrobial effects; Ngwendson JN et al.; The methanol extract of Peucedanum zenkeri L . seeds showed antimicrobial activity which is concentrated in the n-hexane fraction . Bioactivity-guided chromatographic fractionation of the seeds of P . zenkeri led to the isolation and characterization of five major coumarins, umbelliprenin, imperatorin, bergapten, isopimpinellin and byakangelicin, as well as two minor coumarins, 7-methoxy coumarin and 5-hydroxy-8-methoxy psoralen . Amongst the isolated compounds only imperatorin, bergapten and isopimpinellin were found to possess anti-microbial activity. J Prosthodont, 2003 Jun, 12(2), 73 - 81 Postcementation hypersensitivity: scientific data versus dentists' perceptions; Rosenstiel SF et al.; PURPOSE: The purpose of this article was to obtain dentists' opinions via an Internet survey as to the prevalence, causes, and prevention of postcementation sensitivity and compare their responses with published data on the problem . MATERIALS AND METHODS: Information as to respondents opinions of postcementation sensitivity was obtained from an Internet survey asking about their experience and for a ranking of the importance of each of 15 factors . RESULTS: A total of 466 valid responses were received . The incidence of postcementation sensitivity was estimated to be less than 2% by more than 2/3 of the dentists . The factors considered "very important" in reducing sensitivity by more than 50% of the respondents were desiccation, luting agent, occlusion, provisional, and water spray . CONCLUSIONS: Comparing respondents' opinions with published clinical studies, the incidence of postcementation sensitivity appears to be underestimated . There is little published evidence to support the importance of antimicrobials, desensitizing, or bonding agents, although these are considered effective by some dentists . Many respondents consider luting agent to be an important variable. Braz Dent J, 2003, 14(2), 75 - 81 Epub 2003 Oct 03. Effect of caries preventive measures directed to expectant mothers on caries experience in their children; Zanata RL et al.; The aim of this prospective study was to determine the effectiveness of caries preventive measures started during pregnancy on the caries experience of first-time mothers and their infants . Eighty-one pregnant women with low social background were selected on the basis of the presence of active carious lesions and were randomly divided into control (38) and experimental (43) groups . The initial dental status (DMFS and white spot lesions) was established through clinical examination . The prophylactic measures were repeated during pregnancy and 6 and 12 months after delivery . Both groups received primary care intervention . They were instructed in relation to the etiologic factors of dental caries and received oral hygiene kits . Oral hygiene instructions were reinforced through interactive brushing . The experimental group also received antimicrobial treatment (topical application of NaF and iodine solution immediately after prophylaxis and 3 and 5 days later) and restorative care using glass ionomer cement . By the time the children were 2 years of age, 33.3% of the infants in the control group and 14.7% in the experimental group had caries activity . A significant difference in caries prevalence was observed between children with and without visible dental plaque . The mean number of tooth surfaces with carious lesions (including areas of demineralization) was higher among the children in the control group compared to the experimental group (6.3 x 3.2), however, with no statistical significance . Maternal caries increase was a significant factor influencing the caries experience of the children . These data support the evidence of an association between caries prevalence in young children and clinical (dental plaque) and maternal factors. Br J Clin Pharmacol, 1993 Dec, 36(6), 511 - 9 A survey of undergraduate and continuing medical education about antimicrobial chemotherapy in the United Kingdom . British Society of Antimicrobial Chemotherapy Working Party on Antimicrobial Use; Davey P et al.; 1 A questionnaire about undergraduate teaching on antimicrobial chemotherapy was sent to academic Departments of Clinical Pharmacology, Pharmacology and Medical Microbiology throughout the UK . 2 Questionnaires about postgraduate lectures and information circulated to doctors about antimicrobial chemotherapy were sent to Drug Information Centres and Postgraduate Tutors throughout the UK . Review articles and editorials in general medical journals were assessed . 3 The median amount of core undergraduate teaching on antimicrobial chemotherapy was 13.5 h but the range was from 9.0 h to 102.0 h . Content was predominantly oriented towards drugs rather than diseases and towards prescribing in hospital rather than in the community . Most teaching was by formal lecture as part of a core programme . On a scale from 0 to 5 the median emphasis given to individual topics ranged from 2.50 to 3.75 but the range of emphasis given by individual medical schools was wide, for example from 1.00 to 4.50 for teaching on pharmacokinetics . 4 Postgraduate tutors identified advice from local specialists and requests from local practitioners as the most important determinants of content of continuing medical education . Material from drug information centres was predominantly oriented towards discussion of individual drugs rather than management of specific diseases and even this limited survey found evidence of duplication . The UK general medical literature contained a total of 112 reviews or editorials on antimicrobial chemotherapy covering a wide range of topics but these were not, and should not be assumed to be comprehensive . 5 Almost all doctors regularly prescribe antimicrobials and require education about the subject . Wide variations in current medical practice should be addressed explicitly through more extensive use of problem solving . The literature suggests that knowledge is most effectively disseminated through local networks of practitioners . There should be more national co-ordination of the content of information to be disseminated through the existing drug information networks. J Am Acad Dermatol, 2003 Sep, 49(3 Suppl), S227 - 32 Cumulative irritancy comparison of adapalene gel 0.1% versus other retinoid products when applied in combination with topical antimicrobial agents; Brand B et al.; This randomized, investigator-blinded study evaluated the level of skin tolerance to adapalene gel 0.1%, tretinoin cream 0.025%, or tretinoin microsphere gel 0.1% when applied in combination with clindamycin phosphate lotion 1%, erythromycin gel 2%, benzoyl peroxide gel 5%, or erythromycin-benzoyl peroxide gel . A total of 37 subjects underwent daily application of the topical antimicrobial and retinoid products to sites on their upper back under protective patches for approximately 16 hours each day; Friday patches were left in place over the weekend . Testing continued daily for 3 weeks or until discontinuation caused by a severe adverse reaction to any of the test products or to the patch . Adapalene gel 0.1% demonstrated statistically significantly (P <.001) less irritation after repeated application under occlusive conditions than tretinoin cream 0.025% or tretinoin microsphere gel 0.1% . Moreover, the application of adapalene gel 0.1% under these conditions, concomitantly with various antimicrobial agents, was safe and well tolerated in this subject population . In view of its low irritation potential and its efficacy, adapalene gel 0.1%, in combination with antimicrobial agents should be considered for the treatment of acne vulgaris. J Am Acad Dermatol, 2003 Sep, 49(3 Suppl), S200 - 10 A review of the use of combination therapies for the treatment of acne vulgaris; Leyden JJ; Acne is a disease of the pilosebaceous unit, involving abnormalities in sebum production, follicular epithelial desquamation, bacterial proliferation, and inflammation . The major classes of therapeutic agents are topical and systemic retinoids, antimicrobial agents, and systemic hormonal drugs . Combination therapy with a topical retinoid and an antibiotic can normalize follicular epithelial desquamation and reduce bacterial proliferation . The new retinoids (eg, adapalene) have an additional antiinflammatory action along with their effect on the preclinical microcomedo and, coadministered with a topical or an oral antibiotic, are a rational initial therapy for all but the most severe forms of acne . Retinoids can also be used alone for long-term maintenance to prevent the reemergence of comedones and inflammatory acne lesions and to spare the use of antibiotics, thus helping to reduce the risk of bacterial resistance. Biochem Biophys Res Commun, 2003 Sep 26, 309(3), 591 - 7 Solution structure of termite-derived antimicrobial peptide, spinigerin, as determined in SDS micelle by NMR spectroscopy; Lee KH et al.; Spinigerin is a linear antibacterial peptide derived from a termite insect . It consists of 25 amino acids and is devoid of cysteines . Spinigerin displays good lytic activities against Gram-positive and Gram-negative bacteria, but has no hemolytic activities against human erythrocytes . In this study, we present a three-dimensional solution structure of spinigerin in SDS micelles . According to CD data spinigerin has an alpha-helical conformation in the presence of TFE, DPC micelles, and SDS micelles . The three-dimensional structure of spinigerin as determined by NMR spectroscopy contains a stable alpha-helix from Lys4 to Thr23 . Spinigerin (4-21), an 18-residue fragment from Lys4 to Leu21, contains a similar content of alpha-helical structure compared to native spinigerin and was found to retain antibacterial activity, too . Therefore, this alpha-helical structure and the strong electrostatic attraction between four Lys and three Arg residues in spinigerin and the negatively charged polar head groups of the phospholipids on the membrane surface play important roles in disrupting membrane and subsequent cell death. Transplant Proc, 2003 Aug, 35(5), 2006 - 8 Pulmonary nocardiosis in heart transplant recipients: treatment and outcome; Peraira JR et al.; BACKGROUND: Nocardial infections typically affect patients receiving immunosuppressants, occurring early after surgery in 3% to 40% of heart transplant (HTx) recipients . The emergence of antibiotic resistance and occurrence of disease recurrences in AIDS population has engendered controversy about the treatment for immunodepressed HTx patients . METHODS: We present a retrospective study of the diagnosis, treatment and outcome of 560 HTx recipients between 1984 and 2002 . RESULTS: Among the five cases of Nocardia infection (0.9%), three cases developed late after HTx (between 3.1 and 11 years follow-up) . All patients had pulmonary disease and one in addition had subcutaneous nodules . Microbiological diagnosis required open lung biopsy in one case . All patients were treated primarily with trimethoprim-sulphamethoxazole, but evidence of resistance to sulfonamides led us to change the antimicrobial combination in two cases . Four patients who received one year of antibiogram-guided therapy showed complete healing without recidivism . Three patients died, all due to non-related causes, at follow-ups between 1 and 5 years . In one case a cutaneous recurrence of disease was attributed to noncompliance . CONCLUSIONS: Nocardiosis in current HTx is less common than previously reported . Its incidence seems to be delayed in time with modern immunosuppressants . Given the high incidence of sulfamide resistance, treatment must be guided by antibiotic sensitivity . We believe that maintenance therapy for a whole year is the appropriate option in order to avoid recidivism in this population. Transplant Proc, 2003 Aug, 35(5), 1999 - 2000 High incidence of severe infections in heart transplant recipients receiving tacrolimus; Peraira JR et al.; BACKGROUND: Tacrolimus (FK) is being increasingly used as an alternative to cyclosporine (CyA) in heart transplantation (HTx) . It is believed to engender slightly more powerful protection against acute rejection . However, the increased immunosuppression could result in an excess of infectious complications . METHODS: Our study compared the incidence of major infections (MInf), defined as life-threatening infectious episodes requiring admission and intravenous (IV) antimicrobial therapy, among a series of HTx recipients treated with either FK (n=30) or CyA (n=84) . RESULTS: A total of 21 patients received FK in an elective protocol and 9 patients initially treated with CyA were converted to FK . Tacrolimus was combined with azathioprine and prednisone in 21 cases, and with mycophenolate mofetil and steroids in 8 recipients . After a follow-up between 6 and 37 months, 11 patients (37%) in the FK group developed 13 episodes of MInf, most (85%) occurring during the first posttransplant year . Conversely, CyA patients (n=84), a group with similar characteristics and follow-up, showed a MInf incidence of 12% (P<.05) . Among the FK group, the most common site of MInf was pulmonary (69%) . A variety of opportunistic agents caused MInf in 54% of cases, whereas the remaining ones were attributed to nosocomial bacteria . There were three deaths (27% of all MInf), all in azathioprine-treated patients with initial FK therapy . CONCLUSIONS: Tacrolimus therapy seems to be associated with an increased incidence of severe infections in HTx recipients . We recommend aggressive diagnostic and therapeutic approaches for patients on FK who develop signs or symptoms of infection in the first year after HTx. J Chemother, 2003 Aug, 15(4), 342 - 9 Post-exposure effects of cefepime and cefpirome on isogenic Escherichia coli hosts producing SHV-extended-spectrum beta-lactamases; Bedenic B et al.; Persistent suppression of bacterial growth after short antimicrobial exposure is called postantibiotic effect (PAE) . By definition, there should be no subinhibitory concentrations of antimicrobial agent left when the postantibiotic effect starts . However, if subinhibitory concentrations are maintained after removing the antibiotic, the recovery period of the treated cultures is markedly prolonged . This is defined as postantibiotic-sub-MIC-effect (PA-SME) . The aim of this study was to determine the PAE and PA-SME of cefpirome and cefepime on isogenic Escherichia coli strains producing SHV-2, SHV-5, and SHV-12 extended spectrum beta-lactamases (ESBL) compared to a non-ESBL E . coli strain . It was hypothesized that the presence of an ESBL would hydrolyze the cephalosporin molecule before it exerted a toxic effect on the bacterial cell and thus shorten the duration of PA-SME . Cefpirome and cefepime had no PAE against ESBL producing E . coli or it was of a short duration and present only at high antibiotic concentrations, but exposure to subinhibitory concentration of those antibiotics in the PA (postantibiotic) phase resulted in a significant delay of regrowth . The effect was more pronounced with higher concentrations of antibiotics, and uninfluenced by the type of enzyme and the antibiotic . The present study shows that the presence of subinhibitory concentrations of cefepime and cefpirome in the medium after exposure to suprainhibitory concentrations results in a significant delay of regrowth of both ESBL-positive and negative E . coli strains . The production of SHV-2, SHV-5 and SHV-12 ESBLs did not shorten the duration of the PA-SME. J Immunol, 2003 Sep 15, 171(6), 3262 - 9 Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes; Nomura I et al.; Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases . However patients with AD, but not psoriasis, suffer from frequent skin infections . To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays . The expression of innate immune response genes, human beta defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016) . Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005) . By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-alpha, IFN-gamma, and IL-1beta . Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro . We found that IL-13 and IL-4 inhibited TNF-alpha- and IFN-gamma-induced HBD-3 production . These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-alpha and IFN-gamma under inflammatory conditions in AD skin . These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases. J Leukoc Biol, 2004 Jan, 75(1), 39 - 48 Epub 2003 Jul 22. Cathelicidins, multifunctional peptides of the innate immunity; Zanetti M; Cathelicidins comprise a family of mammalian proteins containing a C-terminal cationic antimicrobial domain that becomes active after being freed from the N-terminal cathelin portion of the holoprotein . Many other members of this family have been identified since the first cathelicidin sequences were reported 10 years ago . The mature peptides generally show a wide spectrum of antimicrobial activity and, more recently, some of them have also been found to exert other biological activities . The human cathelicidin peptide LL-37 is chemotactic for neutrophils, monocytes, mast cells, and T cells; induces degranulation of mast cells; alters transcriptional responses in macrophages; stimulates wound vascularization and re-epithelialization of healing skin . The porcine PR-39 has also been involved in a variety of processes, including promotion of wound repair, induction of angiogenesis, neutrophils chemotaxis, and inhibition of the phagocyte NADPH oxidase activity, whereas the bovine BMAP-28 induces apoptosis in transformed cell lines and activated lymphocytes and may thus help with clearance of unwanted cells at inflammation sites . These multiple actions provide evidence for active participation of cathelicidin peptides in the regulation of the antimicrobial host defenses. J Leukoc Biol, 2004 Jan, 75(1), 34 - 8 Epub 2003 Jul 15. Antimicrobial polypeptides; Ganz T; The respiratory tract presents a large and potentially vulnerable surface to inhaled microbes . It is coated by a thin layer of secretions generated by airway epithelial cells, submucosal glands, resident and recruited phagocytes (neutrophils, eosinophils, monocytes, and macrophages) and alveolar epithelial cells, as well as substances that enter from blood plasma . More than 80 years ago, Alexander Fleming observed that respiratory secretions have microbicidal and microbistatic properties . He described the activity of lysozyme, one of the principal polypeptides of these secretions . Since then, a number of additional antimicrobial components have been identified, and there is increasing insight into their complex interactions . This review is an update of my previous summary of this area. J Leukoc Biol, 2003 Oct, 74(4), 542 - 50 Epub 2003 Jul 01. Targeting myeloperoxidase to azurophilic granules in HL-60 cells; Lemansky P et al.; Myeloperoxidase (MPO) is a cationic protein and one of the major constituents of azurophilic granules in neutrophils . Here, we examined whether intracellular transport of MPO and serglycin, a chondroitin sulfate (CS)-bearing proteoglycan, is correlated . First, we examined binding of MPO to CS-Sepharose and measured an ionic interaction, which was disrupted by 200-400 mM NaCl . Next, HL-60 promyelocytes were activated with a phorbol ester, which induced an almost complete rerouting of serglycin from the granular to the secretory pathway, concomitant with a similar effect on MPO transport and secretion . We then used the membrane-permeable cross-linker dithiobis(succininmidylpropionate; DSP) after labeling HL-60 cells with {35S}methionine and {35S}cysteine for 19 h . Immunoprecipitation of MPO revealed its cross-linking to high molecular material having the appearance of a proteoglycan in sodium dodecyl sulfate-polyacrylamide gels . This assumption was confirmed by labeling HL-60 cells with {35S}sulfate for 10 min followed by DSP cross-linking and immunoprecipitation . From three granular enzymes immunoprecipitated, only the cationic MPO was cross-linked to {35S}sulfate-labeled serglycin in appreciable quantities, whereas cathepsin D or beta-N-acetylhexosaminidase was not . Thus, intracellular transport of MPO appears to be linked to that of serglycin . Extracts from high buoyant density organelles from human placenta containing MPO activity were subjected to CS-affinity chromatography . Proteins binding to CS were identified by mass spectrometry as MPO, lactoferrin, cathepsin G, and azurocidin/cationic antimicrobial protein of molecular weight 37 kDa, suggesting that serglycin may be a general transport vehicle for the cationic granular proteins of neutrophils. Biomacromolecules, 2003 Sep-Oct, 4(5), 1264 - 8 Nonnatural branched polysaccharides: synthesis and properties of chitin and chitosan having disaccharide maltose branches; Kurita K et al.; Synthesis and properties of chitin and chitosan derivatives having beta-maltoside branches at C-6 have been studied . Chitosan was first transformed into an organosoluble acceptor having a reactive group only at C-6, 3-O-acetyl-2-N-phthaloyl-6-O-trimethylsilylchitosan . Glycosylation with an ortho ester from d-maltose was performed successfully at room temperature in dichloromethane in the presence of trimethylsilyl trifluoromethanesulfonate as the catalyst . The degree of substitution could be controlled by the reaction conditions and was up to 0.56 . Full deprotection gave chitosan with maltoside branches, and the subsequent N-acetylation resulted in the formation of the corresponding chitin derivative . The introduced disaccharide unit improved hydrophilic properties considerably compared to monosaccharide units as confirmed by high solubility in water and moisture absorption and retention ability . The enzymatic degradability and antimicrobial activity were moderate probably because of the bulky nature of the branches. J Comb Chem, 2003 Sep-Oct, 5(5), 597 - 605 A positional scanning combinatorial library of peptoids as a source of biological active molecules: identification of antimicrobials; Humet M et al.; A positional scanning library of N-alkylglycine trimers (peptoids) containing over 10 000 compounds has been synthesized on solid phase . The synthetic pathway involved the use of the submonomer strategy and a set of 22 commercially available primary amines as a chemical diversity source . The unbiased nature of the library allowed its screening against a variety of biological targets, leading to the identification of individual peptoids exhibiting remarkable biological activities (Garcia-Martinez, C . et al . Proc . Natl . Acad . Sci . U.S.A . 2002, 99, 2374 . Montoliu, et al . J . Pharm . Exp . Therap . 2002, 302, 29 . Planells-Cases, R., et al . J . Pharm . Exp . Therap . 2002, 302, 163) . In the present work, the screening of this library against a panel of Gram-positive and Gram-negative bacteria led to the identification of different compounds exhibiting antimicrobial activity. J Am Vet Med Assoc, 2003 Sep 1, 223(5), 677 - 83 Health performance of feeder calves sold at conventional auctions versus special auctions of vaccinated or conditioned calves in Ontario; Macartney JE et al.; OBJECTIVE: To compare health performance during the first 28 days in the feedlot for vaccinated or conditioned feeder calves sold through special auctions in Ontario with health performance for calves sold through conventional auctions in the province . DESIGN: Cohort study . ANIMALS: 12,313 calves sold through conventional and special auctions at the Keady Livestock Market during the fall of 1999 and 2000 . PROCEDURE: Buyers of calf groups were approached at the auction market or contacted by telephone and asked to record the number of calves requiring treatment for bovine respiratory tract disease (BRD) during the first 28 days after purchase . RESULTS: 211 calf groups (> or = 20 calves/group) were followed up for 28 days after purchase . Multivariate logistic analysis indicated that vaccinated calves purchased through special auctions were 0.68 (95% confidence interval, 0.50 to 0.93) times as likely to receive treatment for BRD as were calves purchased at conventional auctions and that conditioned calves were 0.22 (95% confidence interval, 0.12 to 0.38) times as likely to receive treatment . Groups that received antimicrobials by injection on arrival at the feedlot were 0.64 (95% confidence interval, 0.43 to 0.96) times as likely to be treated as were groups that did not . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that vaccinated and conditioned calves were less likely to receive treatment for BRD during the first 28 days in the feedlot; however, there was no difference in mortality rate. Front Biosci, 2003 Sep 01, 8, s769 - 82 Lyme disease and the heart; Haddad FA et al.; Lyme carditis is typically characterized by varying degrees of intermittent atrioventricular block occurring within weeks of infection with Borrelia burgdorferi . Myocarditis and/or pericarditis may occur . Cardiomyopathy has been associated with B . burgdorferi in Europe, but not in the United States . Patients with unexplained atrioventricular block or myopericarditis should be questioned for recent travel to tick-endemic areas, and for a history of erythema migrans rash, "viral-like" illness, aseptic meningitis, cranial nerve palsy, radiculitis, or oligoarthritis . However, the absence of a recognized tick bite or rash does not rule out Lyme disease . The diagnosis of Lyme carditis should be supported by the presence of concurrent erythema migrans, or by positive results of 2-step laboratory testing for antibodies to B . burgdorferi . False positive results may occur, emphasizing the importance of clinical judgment in attributing specific manifestations to B . burgdorferi infection . Carditis generally resolves spontaneously, but antimicrobial therapy can shorten symptom duration and prevent potential cardiac and non-cardiac sequelae . Cardiac manifestations generally resolve spontaneously, but antimicrobial therapy can shorten symptom duration and prevent potential cardiac and non-cardiac sequelae . The prognosis for Lyme carditis is excellent. Front Biosci, 2003 Sep 01, 8, s862 - 73 Mechanism of antibiotic efflux in Gram-negative bacteria; Zgurskaya HI et al.; Active efflux of antibiotics mediated by multidrug transporters is a mechanistic basis of multidrug resistance in bacteria . The most versatile multidrug transporters are those found in Gram-negative bacteria . They have a high level of constitutive expression and provide an immediate response to structurally diverse antimicrobial agents including clinically important antibiotics . The versatility and efficiency of multidrug transporters in Gram-negative bacteria heavily depend on coupling of drug efflux with the transport across the outer membrane . The coupling is achieved through the assembly of multi-component protein complexes that span both the inner and the outer membranes of Gram-negative bacteria . In this review we discuss the mechanistic and structural features of multidrug efflux complexes with the major focus on the tight coupling of drug efflux with transport across the outer membrane. Int J Dermatol, 2003 Sep, 42(9), 707 - 8 Relapsing polychondritis; Liu CM et al.; A 43-year-old Chilean man presented with a 5-month history of progressive hypertrophy of the ears bilaterally . He was seen initially by a dermatologist in Chile for complaints of erythema and swelling of the ears, and had been treated unsuccessfully with topical steroids and antimicrobial ointments . On presentation to our clinic, the hypertrophy had stabilized and the erythema had resolved, but he complained of decreased hearing due to narrowing of the external auditory canal . Associated symptoms included occasional pruritus, but he denied any pain . He also denied a history of sinus problems, respiratory symptoms, ocular pain, chest pain, and arthralgias . Physical examination revealed firm hypertrophy of the collagenous areas of both ears, sparing the ear lobes (Fig . 1) . No pain was elicited on palpation . No conjunctivitis was noted and the nasal passages were clear . His chest was clear to auscultation . Histologic examination revealed a minimal perivascular infiltrate of lymphocytes and plasma cells in the dermis with fibrosis of the subcutis (Fig . 2) . Blood tests showed a normal complete blood count, antinuclear antibody, and rheumatoid factor . Anti-collagen II antibodies were elevated at 29.2 Eu/ml (normal, 0-20 Eu/ml; borderline, 20-25 Eu/ml; elevated, > 25 Eu/ml). Schweiz Monatsschr Zahnmed, 2003, 113(7), 756 - 63 {Irrigants and intracanal medicaments in endodontics}; Zehnder M et al.; Modern, biologic root canal therapy should be performed with suitable irrigating solutions and intracanal medicaments . The goal of endodontic treatment is to free the treated tooth from infection and prevent reinfection as thoroughly as possible by means which do not put the organism at risk . In this review of the literature, an evidence-based concept for irrigation and medication of root canal systems is presented . Irrigants and medicaments are discussed with respect to their antimicrobial, tissue-dissolving and endotoxin-decontaminating capacity in relation to their systemic toxicity . Recent findings pertaining to interactions of root canal medicaments and irrigating solutions and their impact on a sound irrigating and medicating concept are discussed. J Palliat Care, 2003 Summer, 19(2), 95 - 9 Evaluation of a nystatin-containing mouth rinse for terminally ill patients in palliative care; Butticaz G et al.; PURPOSE: To evaluate the antifungal effect of a nystatin mouth rinse to control oral candidiasis of elderly patients in palliative care . MATERIALS AND METHODS: 52 cancer patients (mean age: 83 years) hospitalized in a long term care facility for chronically ill geriatric patients . Mouth rinsing with 15 ml nystatin solution (4,000 Ul/ml) was carried out for one minute, six times daily, over two weeks . Yeasts were collected and seeded on CHROMagar . Growth was read qualitatively and quantitatively after two days' incubation at 37 degrees C . RESULTS: Clinical signs of oral candidiasis were observed in 31% of cases . High yeast scores were observed in 58% of the residents . There was an association between signs of oral candidiasis and high yeast scores (p < 0.001) . Treatment for two weeks caused no clinical changes nor reduced yeast scores . CONCLUSIONS: No clinical or antifungal effect from the nystatin suspension suggests that the concentration of nystatin in the mouth rinse was too low . A more effective procedure should be employed for antifungal treatment of terminally ill patients . Appropriate antimicrobial solutions with lubricating activity should be developed and applied to prevent oral diseases. Clin Infect Dis, 2003 Sep 15, 37(6), 853 - 6 Epub 2003 Aug 27. Do resident physicians use antibiotics appropriately in treating upper respiratory infections? A survey of 11 programs; Fakih MG et al.; We surveyed resident physicians of 11 primary care programs regarding the management of upper respiratory infections and antibiotic resistance . Although they viewed excess antibiotic use as the most important factor increasing resistance, they had little knowledge regarding antimicrobial resistance and were willing to prescribe antibiotics for common viral illnesses. J Med Chem, 2003 Sep 11, 46(19), 4173 - 81 Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds; Thorsteinsson T et al.; A series of soft quaternary ammonium antimicrobial agents, which are analogues to currently used quaternary ammonium preservatives such as cetyl pyridinium chloride and benzalkonium chloride, were synthesized . These soft analogues consist of long alkyl chain connected to a polar headgroup via chemically labile spacer group . They are characterized by facile nonenzymatic and enzymatic degradation to form their original nontoxic building blocks . However, their chemical stability has to be adequate in order for them to have antimicrobial effects . Stability studies and antibacterial and antiviral activity measurements revealed relationship between activity, lipophilicity, and stability . Their minimum inhibitory concentration (MIC) was as low as 1 microg/mL, and their viral reduction was in some cases greater than 6.7 log . The structure-activity studies demonstrate that the bioactive compounds (i.e., MIC for Gram-positive bacteria of <10 microg/mL) have an alkyl chain length between 12 and 18 carbon atoms, with a polar headgroup preferably of a small quaternary ammonium group, and their acquired inactivation half-life must be greater than 3 h at 60 degrees C. Microbiol Immunol, 2003, 47(7), 527 - 31 Prevalence of inherited myeloperoxidase deficiency in Japan; Nunoi H et al.; The microbicidal activity of the myeloperoxidase (MPO)-hydrogen peroxide-halide system has been implicated as the most efficient, oxygen-dependent antimicrobial component of neutrophil host defense . Unexpectedly, individuals with MPO deficiency suffer few clinical consequences . In order to understand better the clinical impact of MPO deficiency, we surveyed several clinical hematology laboratories in Japan to assess the prevalence of MPO deficiency in the general population . MPO activity was determined by flow cytometry using the Technicon H series of automated systems . We identified 26 cases of complete MPO deficiency, prevalence 1 in 57,135, and 129 cases of partial deficiency, prevalence 1 in 17,501 . The distribution of complete and partial deficiencies differed among the laboratories studied. Ned Tijdschr Tandheelkd, 2003 Aug, 110(8), 321 - 7 {110th volume of Dutch Journal of Dentistry 3 . Developments in the treatment of oral and craniomaxillofacial trauma during the last five decades}; Stoelinga PJ; A historical review is presented on the development of the treatment of trauma of the maxillofacial skeleton in the context of international as well as national literature . The review has been divided in three periods: the period before the prophylactic use of antimicrobial agents (before 1950), the years of open reduction with wire osteosynthesis (1950-1980) and the period till present in which open reduction is combined with rigid internal fixation (after 1980) . The latter period is also marked by the application of the principles of primary bone healing, whereas access to the maxillofacial skeleton is gained through a coronal incision, where needed. Arch Pharm (Weinheim), 2003 Aug, 336(6-7), 336 - 44 Novel high energy intermediate analogues with a triazasterol structure as potential ergosterol biosynthesis inhibitors IV: antimicrobial activity of mono-, bi-, and tricyclic 8, 13, 15-triazasteroid analogues including the synthesis of novel 4-alkylamino- and 4-alkenylamino-9-hydroxypyrimidoisoquinolines; Gossnitzer E et al.; 4-alkylamino-and 4-alkenylamino-9-hydroxy-1, 6, 7, 11b-tetrahydro-2H-pyrimido{4, 3-a}isoquinolines were designed as inhibitory tricyclic triaza-analogues of carbocationic high energy intermediates (HEI) of enzymes involved in fungal ergosterol biosynthesis . Various routes for effective synthesis of 9-hydroxypyrimidoisoquinolines from 9-methoxythiones were investigated . The ether cleavage of 9-methoxy-pyrimidoisoquinolines, a key step in the synthesis, was carried out using various protocols . The structures of the obtained 9-hydroxy compounds were confirmed using homo- and hetero-nuclear correlated 1D and 2D NMR experiments . In vitro antifungal susceptibility tests of the alkylaminohydroxypyrimidoisoquinolines revealed weak to good antimycotic effects . The maximum antifungal efficacy was found for 4-{(3R)-6-isopropyl-3-methyl-6-heptenylamino}-9-hydroxypyrimidoisoquinoline . Furthermore, the in vitro activities of the newly synthesized 9-hydroxypyrimidoisoquinolines and of a series of prepared 8, 13, 15-triazasteroid analogues (N-alkyl-N'-(phenethyl- and cyclohexenylethyl)guanidines, N(2) -and N(2), 4-substituted imidazolin-2-amines, and N(4)-alkylaminopyrimidoisoquinolines) against representatives of gram-positive and gram-negative bacteria were investigated . The compounds showed significant antibacterial effects against gram-positive bacteria. Biosci Biotechnol Biochem, 2003 Aug, 67(8), 1844 - 6 Paradoxical effect of synthetic hydroxy isothiocyanates on antimicrobial action of aminoglycosides; Tajima H et al.; Hydroxy isothiocyanates, especially 2-(4-hydroxyphenyl)ethyl isothiocyanate (hITC), were examined for antimicrobial synergism with streptomycin (SM) against Escherichia coli . On the course of those experiments, a peculiar suppression of SM by a low concentration of hITC was observed, besides the antibacterial synergism of hITC with SM . Further, bactericidal activity of SM in physiological saline was reduced by addition of hITC . Time course experiments proved that the antagonistic effect of hITC occurred in an early stage after exposure of bacterial cells to SM. Biosci Biotechnol Biochem, 2003 Aug, 67(8), 1636 - 42 Purification, characterization, and sequencing of a novel type of antimicrobial peptides, Fa-AMP1 and Fa-AMP2, from seeds of buckwheat (Fagopyrum esculentum Moench.); Fujimura M et al.; Novel antimicrobial peptides (AMP), designated Fa-AMP1 and Fa-AMP2, were purified from the seeds of buckwheat (Fagopyrum esculentum Moench.) by gel filtration on Sephadex G75, ion-exchange HPLC on SP COSMOGEL, and reverse-phase HPLC . They were basic peptides having isoelectric points of over 10 . Fa-AMP1 and Fa-AMP2 had molecular masses of 3,879 Da and 3,906 Da on MALDI-TOF MS analysis, and their extinction coefficients in 1% aqueous solutions at 280 nm were 42.8 and 38.9, respectively . Half of all amino acid residues of Fa-AMP1 and Fa-AMP2 were cysteine and glycine, and they had continuous sequences of cysteine and glycine . The concentrations of peptides required for 50% inhibition (IC50) of the growth of plant pathogenic fungi, and Gram-positive and -negative bacteria were 11 to 36 microg/ml . The structural and antimicrobial characteristics of Fa-AMPs indicated that they are a novel type of antimicrobial peptides belonging to a plant defensin family. J Antimicrob Chemother, 2003 Oct, 52(4), 564 - 71 Epub 2003 Sep 01. Considering resistance in systematic reviews of antibiotic treatment; Leibovici L et al.; CONTEXT: Microorganisms resistant to antibiotic drugs are a threat to the health and chances of survival of patients . Systematic reviews on antibiotic drugs that ignore the topic of resistance present readers with a skewed view, emphasizing short-term efficacy or effectiveness while ignoring long-term consequences . OBJECTIVES: To examine whether systematic reviews of antibiotic treatment consider resistance; if not, to find out whether data on resistance were reported in the original trials; and based on that, to offer a framework for taking resistance into account in systematic reviews . DATA SOURCES: The Cochrane Database of Systematic Reviews (the Cochrane Library, 2001, issue 2); and MEDLINE, 1996-2000 . STUDY SELECTION: (i) Systematic reviews or meta-analyses of antimicrobial therapy, published during 1996-2000 . (ii) Randomized, controlled trials abstracted in systematic reviews that addressed a topic highly relevant to antibiotic resistance . DATA EXTRACTION: We examined each systematic review, and each article, to see whether the implications of resistance were discussed; and whether data on resistance were collected . RESULTS: Out of 111 systematic reviews, only 44 (40%) discussed resistance . Ten reviews (9%) planned or performed collection of data on the response of patients with susceptible or resistant isolates . In 22 systematic reviews (20%), collection of data on induction of resistance was planned or performed . The topic of 41 reviews was judged highly relevant to resistance, and these reviews extracted data from 337 articles, out of which we retrieved 279 articles (83%) . In 201 (72%) articles, resistance was discussed or data pertaining to it were collected . Ninety-seven articles (35%) gave actual data on resistance of pathogens to the study drugs, 71 articles (25%) data on efficacy of antibiotic drugs in patients with susceptible and resistant pathogens, and 55 articles (20%) provided data on infection or colonization with resistant strains during treatment . CONCLUSIONS: Most systematic reviews on antibiotic treatment ignored the issue of resistance, although many of the original articles referred to it and some reported relevant data . Reviewers should collect data on resistance and discuss the implications in their discussion and sections concerned with policy implications. Bioorg Med Chem Lett, 2003 Oct 6, 13(19), 3345 - 50 Muraymycins, novel peptidoglycan biosynthesis inhibitors: synthesis and SAR of their analogues; Yamashita A et al.; A series of Muraymycin analogues was synthesized . These analogues showed excellent antimicrobial activity against gram-positive organisms . These analogues also showed excellent inhibitory activity against the target peptidoglycan biosynthesis enzyme MraY, the cell membrane associated transglycosylase responsible for the formation of Lipid II. Mol Microbiol, 2003 Sep, 49(6), 1547 - 63 Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy; Gao LY et al.; Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually . The unusually low permeability of its cell wall contributes to the ability of M . tuberculosis to grow within host macrophages, a property required for pathogenesis of infection . Mycobacterium marinum is an established model for discovering genes involved in mycobacterial infection . Mycobacterium marinum mutants with transposon insertions in the beta-ketoacyl-acyl carrier protein synthase B gene (kasB) grew poorly in macrophages, although growth in vitro was unaffected . Detailed analyses by thin-layer chromatography, nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, infrared spectroscopy, and chemical degradations showed that the kasB mutants synthesize mycolic acids that are 2-4 carbons shorter than wild type; the defect was localized to the proximal portion of the meromycolate chain . In addition, these mutants showed a significant (approximately 30%) reduction in the abundance of keto-mycolates, with a slight compensatory increase of both alpha- and methoxy-mycolates . Despite these small changes in mycolate length and composition, the kasB mutants exhibited strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensin and lysozyme . The abnormalities of the kasB mutants were fully complemented by expressing M . tuberculosis kasB, but not by the closely related gene kasA . These studies identify kasB as a novel target for therapeutic intervention in mycobacterial diseases. Mycoses, 2003 Sep, 46(8), 351 - 4 Surgical treatment of tinea capitis in childhood; Thoma-Greber E et al.; Fungal infections of the scalp can cause kerion, pus-filled swellings, that may look like bacterial abscesses . We report on two children who underwent incision and drainage of their kerions under local and general anesthesia . This treatment was inappropriate: it carried the risk associated with general anesthesia and surgery without providing the therapeutic chance linked to adequate antimicrobial chemotherapy . We recommend that children who are present at emergency departments with pus-filled swellings on the scalp should be referred to a dermatology unit where appropriate clinical and laboratory investigations and antifungal treatment can be provided, if considered adequate. Helicobacter, 2003 Aug, 8(4), 310 - 9 A prospective, randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin; Miehlke S et al.; BACKGROUND AND AIM: Failure of primary anti-H . pylori therapy results in a high rate of antimicrobial resistance . Here, we investigated the efficacy of high-dose dual therapy and quadruple therapy as salvage treatments for eradication of H . pylori resistant to both metronidazole and clarithromycin . PATIENTS AND METHODS: Patients with at least one treatment failure and infected with H . pylori resistant to both metronidazole and clarithromycin, were randomized to receive either omeprazole 4 x 40 mg and amoxicillin 4 x 750 mg; or omeprazole 2 x 20 mg, bismuthcitrate 4 x 107 mg, metronidazole 4 x 500 mg and tetracycline 4 x 500 mg . Both regimens were given for 14 days . In cases of persistent infection, a cross-over therapy was performed . RESULTS: Eighty-four patients were randomized . Cure of H . pylori infection was achieved in 31 patients after dual therapy and in 35 patients after quadruple therapy (per protocol: 83.8% (95% CI, 67.9-93.8) and 92.1% (95% CI, 78.6-98.3), respectively (p=0.71); intention to treat: 75.6% (95% CI: 59.7-87.6) and 81.4% (95% CI: 66.6-91.6), respectively (p=0.60)) . Cross-over therapy was performed in six of nine patients, four of whom were cured of the infection . CONCLUSION: Both high-dose dual therapy and quadruple therapy are effective in curing H . pylori infection resistant to both metronidazole and clarithromycin in patients who experienced previous treatment failures. Clin Exp Dermatol, 2003 Sep, 28(5), 549 - 53 Parental knowledge of topical therapies in the treatment of childhood atopic dermatitis; Beattie PE et al.; Poor adherence with therapy is a major cause of treatment failure in atopic dermatitis . Reasons given are multifactorial, and include fear of real or imaginary side-effects, under-prescribing, failure to renew prescriptions on time, lack of time, and child refusal of therapy . Most important, however, is lack of knowledge about treatment, in particular the use of topical corticosteroid (TCS) therapy . We conducted a questionnaire-based study to determine the level of use and knowledge of commonly prescribed TCS preparations amongst parents or carers of 100 children attending paediatric outpatient clinics . Weakly potent TCSs were the most commonly used (86%), but poorly understood . Only 35 (41%) who had used hydrocortisone were aware that it was weakly potent, and 44% graded it as moderately potent . Of 65 who had used the moderately potent TCS clobetasone butyrate 0.05% (Eumovate); Glaxo Wellcome, Uxbridge, UK), 19 (29%) graded it as potent and eight (12%) as weak . Of 50 who had used betamethasone valerate 0.1% (Betnovate); Glaxo Wellcome, Uxbridge, UK), 42% did not grade it as potent . Understanding of TCS/antimicrobial combinations was generally worse . The hydrocortisone 1%/fusidic acid 2% combination (Fucidin H(R); Leo, Risborough, Bucks, UK) was graded as moderate or strong by 88% of the 74 who had used it . Over half (53%) of the 34 using the combination of clobetasone butyrate 0.05%/nystatin 100000 i.u./g tetracycline 3% (Trimovate); Glaxo Wellcome, Uxbridge, UK) assumed that it was a potent TCS . Forty-nine had used Fucibet (betamethasone valerate 0.1%, fusidic acid 2%; Leo, Risborough, Bucks, UK) but 34.5% did not grade it as potent . There was poor knowledge of the strengths of some of the most commonly used TCSs, and all steroid/antimicrobial combinations were perceived as being of greater potency than the constituent steroid alone . Fusidic acid was thought to be a steroid by almost half (46.9%) of the respondents . The packaging of the different products by some pharmaceutical companies is remarkably similar and labelling contains information on the compound and percentage rather than potency of the TCS . This may be a source of confusion . We recommend that manufacturers clearly label TCS products by potency as mild, moderate, potent or very potent and that packaging is sufficiently different for each strength of TCS or emollient to avoid confusion . In order to achieve optimal topical treatment for atopic dermatitis, patients and their carers must receive adequate information and training in how and when to use topical therapies in conjunction with written care plans. Eur J Biochem, 2003 Sep, 270(18), 3720 - 30 Identification, structure and differential expression of novel pleurocidins clustered on the genome of the winter flounder, Pseudopleuronectes americanus (Walbaum); Douglas SE et al.; Antimicrobial peptides form one of the first lines of defense against invading pathogens by killing the microorganisms and/or mobilizing the host innate immune system . Although over 800 antimicrobial peptides have been isolated from many different species, especially insects, few have been reported from marine fish . Sequence analysis of two genomic clones (15.6 and 12.5 kb) from the winter flounder, Pseudopleuronectes americanus (Walbaum) resulted in the identification of multiple clustered genes for novel pleurocidin-like antimicrobial peptides . Four genes and three pseudogenes (Psi) are encoded in these clusters, all of which have similar intron/exon boundaries but specify putative antimicrobial peptides differing in sequence . Pseudogenes are easily detectable but have incorrect initiator codons (ACG) and often contain a frameshift(s) . Potential promoters and binding sites for transcription factors implicated in regulation of expression of immune-related genes have been identified in upstream regions by comparative genomics . Using reverse transcription-PCR assays, we have shown for the first time that each gene is expressed in a tissue-specific and developmental stage-specific manner . In addition, synthetic peptides based on the sequences of both genes and pseudogenes have been produced and tested for antimicrobial activity . These data can be used as a basis for prediction of antimicrobial peptide candidates for both human and nonhuman therapeutants from genomic sequences and will aid in understanding the evolution and transcriptional regulation of expression of these peptides. Nat Rev Immunol, 2003 Sep, 3(9), 710 - 20 Defensins: antimicrobial peptides of innate immunity; Ganz T; The production of natural antibiotic peptides has emerged as an important mechanism of innate immunity in plants and animals . Defensins are diverse members of a large family of antimicrobial peptides, contributing to the antimicrobial action of granulocytes, mucosal host defence in the small intestine and epithelial host defence in the skin and elsewhere . This review, inspired by a spate of recent studies of defensins in human diseases and animal models, focuses on the biological function of defensins. Pediatrics, 2003 Sep, 112(3 Pt 1), 620 - 7 Reduction in antibiotic use among US children, 1996-2000; Finkelstein JA et al.; BACKGROUND: High rates of antibiotic prescribing to children contribute to antibiotic resistance in the community . The Centers for Disease Control and Prevention, in collaboration with other national and state level organizations, have actively promoted more judicious prescribing for children . OBJECTIVE: We sought to assess changes in the rate of antibiotic prescribing from 1996-2000 in 9 US health plans, patterns of diagnosis and treatment responsible for these trends, and changes in the use of first-line antimicrobial agents . DESIGN/METHODS: We analyzed claims data for dispensed medications and physician visits from 9 health plans . Each provided data on 25,000 children aged 3 months to <18 years enrolled between September 1, 1995, and August 31, 2000 . Antibiotic dispensings were linked with an ambulatory visit claim to assign diagnosis . Antibiotic dispensings per person-year (antibiotics/p-y) were calculated for the age groups 3 months to <3 years, 3 years to <6 years, and 6 years to <18 years . The contribution of each diagnosis to changes in the overall rate of antibiotic use was determined . Generalized linear mixed models were used to test for trend and assess differences in rates by site . RESULTS: From 1996-2000, antibiotic rates for children 3 months to <3 years decreased from 2.46 to 1.89 antibiotics/p-y (24%); for children 3 years to <6 years from 1.47 to 1.09 antibiotics/p-y (25%); and for children 6 to <18 years from 0.85 to 0.69 antibiotics/p-y (16%) . The reduction varied among health plans from 6% to 39% for children 3 months to <3 years . A decrease in prescriptions for otitis media accounted for 59% of the total decrease, and was primarily accounted for by a decrease in the rate of diagnosis of this condition . The proportion of first-line penicillins increased from 49% to 53%, with health plans with the lowest initial rates increasing most . CONCLUSIONS: Antibiotic prescribing decreased significantly between 1996 and 2000, concurrent with decreased frequency of diagnosis of potential bacterial infections, especially otitis media . Attention by public health and professional organizations and the news media to antibiotic resistance may have contributed to changes in diagnostic thresholds, resulting in more judicious prescribing. J Bacteriol, 2003 Sep, 185(18), 5349 - 56 Chimeric analysis of AcrA function reveals the importance of its C-terminal domain in its interaction with the AcrB multidrug efflux pump; Elkins CA et al.; AcrAB-TolC is the major, constitutively expressed efflux protein complex that provides resistance to a variety of antimicrobial agents in Escherichia coli . Previous studies showed that AcrA, a periplasmic protein of the membrane fusion protein family, could function with at least two other resistance-nodulation-division family pumps, AcrD and AcrF, in addition to its cognate partner, AcrB . We found that, among other E . coli resistance-nodulation-division pumps, YhiV, but not MdtB or MdtC, could also function with AcrA . When AcrB was assessed for the capacity to function with AcrA homologs, only AcrE, but not YhiU or MdtA, could complement an AcrA deficiency . Since AcrA could, but YhiU could not, function with AcrB, we engineered a series of chimeric mutants of these proteins in order to determine the domain(s) of AcrA that is required for its support of AcrB function . The 290-residue N-terminal segment of the 398-residue protein AcrA could be replaced with a sequence coding for the corresponding region of YhiU, but replacement of the region between residues 290 and 357 produced a protein incapable of functioning with AcrB . In contrast, the replacement of residues 357 through 397 of AcrA still produced a functional protein . We conclude that a small region of AcrA close to, but not at, its C terminus is involved in the interaction with its cognate pump protein, AcrB. Biochim Biophys Acta, 2003 Sep 2, 1615(1-2), 84 - 92 The role of the abundant phenylalanines in the mode of action of the antimicrobial peptide clavanin; van Kan EJ et al.; Clavanin A is a special antimicrobial peptide that acts at the level of the membrane via a pH-dependent mechanism . At neutral pH, clavanin disrupts biological and model membranes in a nonspecific manner, causing efflux of large molecules . At mildly acidic conditions, however, the peptide efficiently kills bacteria by permeabilizing their membrane most likely by interacting with proteins involved in proton translocation {Biochemistry 41 (2002) 7529} . Clavanin A is unusually rich in phenylalanines with 5 out of 23 residues, which suggests that these residues are functionally important . A set of mutants, in which all Phe residues are replaced by either Ile, Leu, Trp, or Tyr was used to investigate the role of these amino acids . The antimicrobial activities of the different peptides both at neutral and low pH show that the presence of phenylalanine is not essential nor optimal, as the Trp, Leu, and Ile mutant are equally or more active than the wild-type component . In general, at neutral pH, the biological activities correlate well with the peptides' ability to interact with membrane lipids . Correspondingly, the permeabilization efficiencies of biological and model membranes of the various derivatives were found to be closely related to their ability to adopt alpha-helical structures, and follows the order 5L>5W>5I>5Y>wild type . The results suggest an important role for the Phe residues, in providing the peptide in a balanced manner with sufficient hydrophobicity, and therewith membrane affinity, as well as conformational flexibility. Cytokine Growth Factor Rev, 2003 Oct, 14(5), 409 - 26 The CC chemokine CCL20 and its receptor CCR6; Schutyser E et al.; CCL20, alternatively named liver and activation-regulated chemokine (LARC), macrophage inflammatory protein-3alpha (MIP-3alpha) or Exodus-1, is the only chemokine known to interact with CC chemokine receptor 6 (CCR6), a property shared with the antimicrobial beta-defensins . The ligand-receptor pair CCL20-CCR6 is responsible for the chemoattraction of immature dendritic cells (DC), effector/memory T-cells and B-cells and plays a role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and rheumatoid arthritis . In this review, the discovery, the gene and protein structure, the in vitro biological activities, the cell and inducer specific expression and the tissue distribution of CCL20 and CCR6 are discussed. Biochemistry (Mosc), 2003 Aug, 68(8), 857 - 61 Antimicrobial peptides containing arginine; Ryadnov MG et al.; Tetradecapeptides (RLARLAR)2, D-(RLARLAR)2, (RLARLAA)2, and (RLGRLGR)2 were synthesized by a solid phase method using Fmoc-amino acids . The antibacterial activity of the synthesized peptides was studied against Escherichia coli cells . The minimum inhibitory concentration (MIC) was, correspondingly, 3, 1, 3, and 12 micro M, which is comparable with MIC of such natural antimicrobial peptides as temporin, magainin, and dermaseptin . It was found that all of the synthesized peptides have no effect on human erythrocytes and rat thymocytes . The peptides form alpha-helices in 30% trifluoroethanol and in 2.5 mM SDS, which have amphipathic structure. J Med Assoc Thai, 2003 Aug, 86(8), 772 - 80 Rapidly growing mycobacterial infections: spectrum of diseases, antimicrobial susceptibility, pathology and treatment outcomes; Sungkanuparph S et al.; OBJECTIVES: A series of cases infected with rapidly growing mycobacteria were studied to reveal the spectrum of disease, antimicrobial susceptibility, pathology, and treatment outcomes . METHOD: The cases identified as rapidly growing mycobacterial infections in Ramathibodi Hospital from January 1993 to June 1999 were retrospectively studied . RESULTS: There were 20 patients and most of the cases had no underlying disease . Only two cases were HIV-infected patients . The presenting clinical features were lymphadenitis (7), skin and subcutaneous abscess (7), eye infection (4), pulmonary infection (1), and chronic otitis media (1) . Four of the seven cases with lymphadenitis had Sweet's syndrome . The organisms were Mycobacterium chelonae/abscessus group (17 cases) and Mycobacteriumfortuitum group (3 cases) . The organisms were susceptible to amikacin, netilmicin and imipenem . The M . fortuitum group was susceptible to more antibiotics than the M . chelonaelabscessus group . Pathology of the infected tissue varied from non-specific findings to suppurative or caseous granuloma . The clinical responses corresponded to the antimicrobial susceptibility . Most of the patients had a good clinical outcome . A combination of two or more drugs was used for the medical treatment . Surgical resection was performed where possible to reduce the load of the organism, especially in cases with very resistant organisms . CONCLUSIONS: Rapidly growing mycobacterial infections can occur in apparently normal hosts . Clinical syndrome is variable . The pathology is non-specific and culture is needed for definite diagnosis . Clinical responses varied but seemed to correlate with the in vitro susceptibility result . More studies are needed before one can deal with these infections more effectively. J Vet Med A Physiol Pathol Clin Med, 2003 May, 50(4), 219 - 21 Mandibular pyogranulomatous osteomyelitis in a Sannen goat; Seifi HA et al.; Mandibular pyogranulomatous osteomyelitis was diagnosed in a female Sannen goat . The doe presented for difficulty prehending and chewing food . The left mandible was swollen and firm on palpation . Radiographs revealed changes consistent with osteomyelitis of the affected mandible . Arcanobacterium pyogenes was isolated from aspirates of swollen mandible . Despite antimicrobial therapy, the goat died . Histopathological findings were consistent with pyogranulomatous disease of the affected mandible . The histopathological findings were similar to those reported for actinomycosis, caused by Actinomyces bovis . Mandibular osteomyelitis is a common condition in cattle and very rare in goat. Pharm Res, 2003 Aug, 20(8), 1149 - 55 Predicting oral absorption of drugs: a case study with a novel class of antimicrobial agents; Hilgers AR et al.; PURPOSE: The purpose of this work was to evaluate an oral absorption prediction model, maximum absorbable dose (MAD), which predicts a theoretical dose of drug that could be absorbed across rat intestine based on consideration of intestinal permeability, solute solubility, intestinal volume, and residence time . METHODS: In the present study, Caco-2 cell permeability, as a surrogate for rat intestinal permeability, and aqueous solubility were measured for 27 oxazolidinones . The oxazolidinones are a novel class of potential antibacterial agents currently under investigation . These values were used to estimate MAD for each of the compounds . Finally, these predicted values were compared to previously measured bioavailability data in the rat in order to estimate oral absorption properties . RESULTS: A reasonably good correlation between predicted dose absorbed and bioavailability was observed for most of the compounds . In a few cases involving relatively insoluble compounds, absorption was underestimated . For these compounds while aqueous solubility was low . solubility in 5% polysorbate 80 was significantly higher, a solvent possibly more representative of the small intestinal lumen . CONCLUSIONS: These results suggest that MAD may be useful for prioritizing early discovery candidates with respect to oral absorption potential . In the case of compounds with poor aqueous solubility, additional factors may have to be considered such as solubility in the intestinal lumen. Sichuan Da Xue Xue Bao Yi Xue Ban, 2003 Apr, 34(2), 217 - 9 {The human beta-defensins expression in female genital tract and pregnancy-related tissues}; Feng Y et al.; OBJECTIVE: Human beta-defensins (HBDs) are small, cationic endogenous antimicrobial peptides isolated from the hemodialates of patients with chronic renal failure (HBD-1) and Psoriasic skin (HBD-2) . They may play an important role in mucosal innate host defense against infections . In this study, we examined their mRNAs expression in normal and pregnant women genital tract . METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was performed in the detection of HBD-1 and HBD-2 mRNA expression in the samples from normal and pregnant women genital tract . beta-actin was taken as positive control . RESULTS: RT-PCR detection revealed that HBD-1 mRNA expressed in all samples of normal women taken from vagina, cervix, endometrium, fallopian tube, and ovary, and HBD-2 mRNA widely expressed in genital tract except vagina and ovary . In pregnant women, HBD-1 mRNA widely expressed in chorion, villus, placenta, and umbilical cord, but not in amnion, and HBD-2 mRNA were detected in chorion, villus and placenta tissues . CONCLUSION: The findings of this study on the wide expression of HBD-1 and HBD-2 in both the normal and the pregnant women genital tract suggest that HBDs may play an important role in human genital tract defense mechanisms. Fitoterapia, 2003 Sep, 74(6), 606 - 8 Antibacterial activity of fresh flower heads of Chrysantemum coronarium; Urzua A et al.; The antibacterial activity of the methylene chloride and methanol extracts of Chrysantemum coronarium fresh flower heads was investigated . The methylene chloride extract showed discrete antimicrobial activity. Clin Ther, 2003 Jul, 25(7), 1936 - 51 Accurate diagnosis and appropriate treatment of acute bacterial rhinosinusitis: minimizing bacterial resistance; Garau J et al.; BACKGROUND: Antimicrobial resistance in respiratory pathogens has become a common clinical problem that has serious public health implications . Inappropriate use of antibiotics for the treatment of viral upper respiratory tract infections (URTIs) has contributed to the development of resistant microorganisms . Health care providers can help control the spread of resistance by limiting the use of antimicrobial agents to infections that meet clinical guidelines for a bacterial cause . OBJECTIVE: This article examines the means of accurately diagnosing and appropriately treating acute bacterial rhinosinusitis (ABRS) in an effort to control increasing levels of resistance . METHODS: This article discusses current treatment guidelines that provide the evidenced-based rationale for choosing the most appropriate antimicrobial agents for suspected ABRS in adults and children . An evidence-based approach can help minimize the public health threat posed by the continuing increase in microbial resistance . RESULTS: Although definitive clinical criteria that differentiate between ABRS and viral URTI are lacking, careful evaluation of the duration and severity of symptoms provides a rational basis for diagnosing ABRS in primary care settings . CONCLUSIONS: Once a diagnosis of ABRS has been made, empiric antibiotic therapy may be justified . When it is, the first-line agent should be the narrowest spectrum antibiotic that would be expected to eradicate the most common causative organisms . The antibiotic selection process should take into account prevailing patterns of resistance and the presence of risk factors for infection with resistant pathogens, as well as published evidence-based guidelines. Arch Pathol Lab Med, 2003 Sep, 127(9), 1112 - 20 Application of rapid-cycle real-time polymerase chain reaction for diagnostic testing in the clinical microbiology laboratory; Cockerill FR 3rd; CONTEXT: Rapid-cycle real-time polymerase chain reaction (PCR) technology combines rapid thermocycling with real-time fluorescent probe detection of amplified target nucleic acids . OBJECTIVES: To review and compare the method of rapid-cycle real-time PCR to conventional PCR methods . To describe the application of rapid-cycle real-time PCR for diagnostic testing in the microbiology laboratory . DATA SELECTION: Information is presented from published literature as well as from personal experience at the Mayo Clinical Microbiology Laboratory (Rochester, Minn) . CONCLUSIONS: Compared to conventional PCR methods, rapid-cycle real-time PCR diagnostics are much faster and easier to perform, and, because both PCR and probe detection occur in the same reaction vessel, the possibility of amplified product (amplicon) contamination is lessened . Furthermore, compared to conventional culture-based or direct antigen detection methods, rapid-cycle real-time PCR assays are frequently more sensitive and much more rapid techniques for detecting or quantifying microorganisms in human samples and for identifying genes or mutations in pathogens associated with antimicrobial resistance. Eur Respir J Suppl, 2003 Aug, 42, 77s - 83s Diagnosis and treatment of nosocomial pneumonia in ALI/ARDS patients; Fagon JY et al.; Ventilator-associated pneumonia (VAP) is a common complication of the acute respiratory distress syndrome (ARDS) or acute lung injury (ALI), often leading to the development of sepsis, multiple organ failure, and death . However, the diagnosis of pulmonary infection in patients with ARDS/ALI is often difficult: the systemic signs of infection, such as fever, tachycardia, leukocytosis are nonspecific findings in such patients; a variety of causes other than pneumonia can explain asymmetric consolidation in patients with ARDS and marked asymmetry of radiographic abnormalities has also been reported in patients with uncomplicated ARDS . In 2003, physicians in charge of these patients have to identify patients with true bacterial lung infection, to select appropriate initial antibiotic therapy, to adjust therapy as soon as possible, and to withhold antibiotics in patients without VAP . To do that, a bacteriological strategy based on the use of quantitative cultures of specimen obtained with fibreoptic bronchoscopy performed before initiation or modification of antibiotic treatment seems better than a strategy based on clinical evaluation alone, lowering antibiotic consumption and improving outcome . When bronchoscopy is not available or contraindicated, a nonbronchoscopic strategy or a clinical strategy with reevaluation 3 days after initiation of treatment may be used . Antimicrobial treatment of VAP is a complex issue . Some general principles can be helpful for the selection of initial treatment: knowledge of most frequently identified responsible pathogens and their susceptibility patterns in the unit; prior duration of hospitalisation; previously prescribed antibiotics; information obtained by direct examination of pulmonary secretions; antibacterial activity and pharmacodynamic characteristics of antibiotics that could be used to treat this infection . Appropriateness of initial antimicrobial therapy is probably a major prognostic factor for patients with ventilator-associated pneumonia . Thus, before new antiboitics are administered, reliable pulmonary specimens must be obtained for direct examination and cultures. Tsitol Genet, 2003 May-Jun, 37(3), 30 - 5 {Role of active forms of oxygen in the induction of phytoalexin synthesis in Allium cepa cells}; Kravchuk ZhM et al.; The results of studies on the role of plant superoxidesynthase signal system in elicitation of antimicrobial phytoalexin (PA) synthesis in cultured Allium cepa cells are presented . Exogenic application of O2- and H2O2 generators results in formation of PA--Tcibulins 1D and 2 {symbol: see text} in A . cepa cells . The mechanism of PA elicitation does not require peroxidase activity . However, the inhibition of one of the possible sources of the reactive oxygen, HADPH oxidase, suppresses elicitor-stimulated PA production . "Oxidative burst" modulation by different chemical compounds in A . cepa cells results in changes of PA synthesis elicitation . The results obtained suggest the tough correlation between "oxidative burst" and elicitation of defense responses, PA synthesis in particular. Can Respir J, 2003 Jul-Aug, 10 Suppl B, 3B - 32B Canadian guidelines for the management of acute exacerbations of chronic bronchitis; Balter MS et al.; Acute exacerbations of chronic bronchitis (AECB) account for over 1.5 million physician visits annually in Canada and are a cause of significant morbidity and mortality . This document represents a joint effort between respirologists, microbiologists, infectious disease specialists and family physicians to update the Canadian AECB guidelines published in 1994 . Treatment recommendations are graded on the strength of evidence in the published literature where possible . The role for oral corticosteroid therapy in preventing treatment failures, speeding up recovery and delaying the time to next exacerbation is discussed . Risk factors for treatment failure were used to stratify patients into risk groups to help guide antibiotic treatment recommendations . The importance of emerging antimicrobial resistance to current antibiotics is reviewed and strategies to prevent future AECB episodes are suggested. J Int Assoc Physicians AIDS Care (Chic Ill), 2002 Oct-Dec, 1(4), 141 - 5 Once-daily antiretroviral therapies for HIV infection: Consensus Statement of an Advisory Committee of the International Association of Physicians in AIDS Care; Cohen C et al.; OBJECTIVE: Adherence is essential to successful virologic outcome of highly active antiretroviral therapy (HAART) . Documented factors contributing to poor adherence include toxicity, food requirements, and pill burden . Once-daily antiretroviral therapies for HIV infection offer potential benefit by decreasing pill burden and dosing frequency, which may subsequently improve treatment adherence . This Consensus Statement is intended to offer guidance to physicians actively involved in HIV/AIDS care . PARTICIPANTS: Eight physicians with expertise in HIV medicine were invited by the International Association of Physicians in AIDS Care (IAPAC) to serve on an ad hoc Advisory Committee . CONSENSUS PROCESS: IAPAC convened the Advisory Committee in June 2002 to develop a draft Consensus Statement . Scientific and clinical research, and other data in published literature and abstracts from scientific conferences were considered by strength of evidence . A Subcommittee updated the Consensus Statement in October 2002 to reflect relevant data presented at the XIV International AIDS Conference and the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy . This document represents consensus agreement of the Advisory Committee . CONFLICT OF INTEREST DISCLOSURE: The International Association of Physicians in AIDS Care sponsored and coordinated the development of this Consensus Statement with an unrestricted educational grant from Bristol-Myers Squibb . The opinions expressed in this Consensus Statement represent only those of the Advisory Committee. Clin Oral Investig, 2003 Dec, 7(4), 217 - 21 Epub 2003 Aug 26. Multifactorial assessment of predictors for prevention of periodontal disease progression; Ehmke B et al.; Univariate approaches have identified single factors influencing periodontal disease progression . The aim of this explorative approach was to assess the influence of various predictive factors responsible for the prevention of periodontal disease progression in the same patient sample . Patients with untreated chronic periodontitis underwent subgingival debridement alone or in combination with adjunctive antimicrobial therapy (systemic amoxicillin and metronidazole/7 days plus supragingival CHX irrigation) . Supportive periodontal therapy was performed over a 24-month period . As predictors, clinical, microbial, immunological, and genetic parameters were assessed . The primary outcome variable was the percentage of teeth without attachment loss >/=2 mm over the study period (stability of attachment) . At 24 months, multiple regression analysis identified adjunctive antimicrobial therapy for teeth with initially at least one site showing a pocket probing depth of >/=7 mm and IgG(4) reactivity against a 110-kDa protein of A . actinomycetemcomitans at teeth with initial pocket probing depths </=6 mm as main predictors of long-term attachment stability ( p<0.05) . Other parameters failed to influence treatment outcome . Adjunctive antimicrobial therapy and antibody reactivity may be dominant factors influencing the prevention of attachment loss in patients receiving periodontal therapy. Curr Opin Microbiol, 2003 Aug, 6(4), 327 - 31 Knocking on the right door and making a comfortable home: Histoplasma capsulatum intracellular pathogenesis; Woods JP; Histoplasma capsulatum is a successful intracellular pathogen of mammalian macrophages . As such, this fungus must survive and/or subvert hostile environmental onslaughts in a professionally antimicrobial host cell . H . capsulatum uses different host receptors for binding to macrophages (beta 2 integrins) than it uses for binding to dendritic cells (the fibronectin receptor); the fungus experiences different degrees of success in survival in these two cells . Surface expression of HSP60 as the specific adhesin for macrophage beta 2 integrins represents a novel mechanism for binding . Long considered a resident of the phagolysosome, H . capsulatum may also reside in a modified phagosome without experiencing phagolysosomal fusion . H . capsulatum must compete with the host to acquire the essential nutrient iron, and has several potential mechanisms for accomplishing this necessary feat . Finally, H . capsulatum displays morphotype-specific expression of several genes, and a calcium-binding protein expressed only by the pathogenic yeast phase has been demonstrated as essential for full virulence . An organism's environment is of great importance to its success or failure, and H . capsulatum is good at finding or making the right environment in the host. J Dent Res, 2003 Sep, 82(9), 719 - 24 Alteration in salivary function in early HIV infection; Lin AL et al.; The etiology of salivary gland hypofunction in HIV(+) patients is unclear . This study was designed to determine the effect of early-stage HIV(+) infection (CD4(+) > 200 cells/ micro L; n = 139) on salivary gland function and the relationship of this dysfunction to the taking of xerostomic medications . Salivary flow rates and the content of electrolytes and antimicrobial proteins in stimulated parotid and submandibular/sublingual saliva were determined . Compared with healthy controls (n = 50), the HIV(+) group showed significant reductions in flow rates of unstimulated whole (35%), stimulated parotid (47%), unstimulated submandibular/sublingual (23%), and stimulated submandibular/sublingual (39%) saliva . The flow rates for the HIV(+) patients taking xerostomic medications did not differ from those of patients who did not . Concentrations of some salivary gland components were altered in the HIV(+) group . Analysis of these data suggests that salivary gland function is adversely affected early in HIV infection and that these changes do not appear to be compounded by the taking of xerostomic medications. Biochemistry, 2003 Sep 2, 42(34), 10311 - 23 Helical structure of dermaseptin B2 in a membrane-mimetic environment; Lequin O et al.; Dermaseptins are antimicrobial peptides from frog skin that have high membrane-lytic activity against a broad spectrum of microorganisms . The structure of dermaseptin B2 in aqueous solution, in TFE/water mixtures, and in micellar and nonmicellar SDS was analyzed by CD, FTIR, fluorescence, and NMR spectroscopy combined with molecular dynamics calculations . Dermaseptin B2 is unstructured in water, but helical conformations, mostly in segment 3-18, are stabilized by addition of TFE . SDS titration showed that dermaseptin B2 assumes nonhelical structures at SDS concentrations far below the critical micellar concentration and helical structures at micellar concentrations . Dermaseptin B2 bound to SDS micelles (0.4 mM peptide, 80 mM SDS) adopts a well-defined amphipathic helix between residues 11-31 connected to a more flexible helical segment spanning residues 1-8 by a flexible hinge region around Val9 and Gly10 . Experiments using paramagnetic probes showed that dermaseptin B2 lies near the surface of SDS micelles and that residue Trp3 is buried in the SDS micelle, but close to the surface . A slow exchange equilibrium occurs at higher peptide/SDS ratios (2 mM peptide, 80 mM SDS) between forms having distinct sets of resonances in the N-terminal 1-11 segment . This equilibrium could reflect different oligomeric states of dermaseptin B2 interacting with SDS micelles . Structure-activity studies on dermaseptin B2 analogues showed that the N-terminal 1-11 segment is an absolute requirement for antibacterial activity, while the C-terminal 10-33 region is also important for full antibiotic activity. Z Naturforsch {C}, 2003 Jul-Aug, 58(7-8), 553 - 7 Lignans, phenylpropanoids and polyacetylenes from Chaerophyllum aureum L . (Apiaceae); Rollinger JM et al.; Sub-aerial parts of Chaerophyllum aureum L . yielded two polyacetylenes, falcarinol (1), falcarindiol (2), three lignans, namely nemerosin (3), deoxypodorhizone (4), deoxypodo-phyllotoxin (5), two phenylpropanoids, 1'-hydroxymyristicin (6) and its angeloyl ester (7) . Compounds 6 and 7 were isolated for the first time from plant material and their structures were elucidated by means of extensive 1- and 2-dimensional NMR spectroscopy and high resolution mass spectrometry . In bioautographic tests on TLC plates the dichloromethane extract showed a significant antimicrobial activity . Falcarindiol was identified as the main active principle whereas the phenylpropanoids and lignans showed no activity. Med Device Technol, 2001 Oct, 12(8), 26 - 30 Antimicrobial coatings: a remedy for medical device-related infections; Lin TL et al.; This article discusses the mechanisms involved in the different approaches to antimicrobial coatings and reports on a new application that seems to offer an antimicrobial surface that is effective for long-term medical implants and suitable for a variety of drugs. Braz J Med Biol Res, 2003 Sep, 36(9), 1215 - 9 Epub 2003 Aug 19. Immunomodulatory properties of Alternanthera tenella Colla aqueous extracts in mice; Guerra RN et al.; Plants from the genus Alternanthera are thought to possess antimicrobial and antiviral properties . In Brazilian folk medicine, the aqueous extract of A . tenella Colla is used for its anti-inflammatory activity . The present study investigated the immunomodulatory property of A . tenella extract by evaluating the antibody production in male albino Swiss mice weighing 20-25 g (10 per group) . The animals received standard laboratory diet and water ad libitum . The effect of A . tenella extract (5 and 50 mg/kg, ip) was evaluated in mice immunized with sheep red blood cells (SRBC 10%, ip) as T-dependent antigen, or in mice stimulated with mitogens (10 micro g, Escherichia coli lipopolysaccharide, LPS, ip) . The same doses (5 and 50 mg/kg, ip) of A . tenella extract were also tested for antitumor activity, using the Ehrlich ascites carcinoma as model . The results showed that 50 mg/kg A . tenella extract ip significantly enhanced IgM (64%) and IgG2a (50%) antibody production in mice treated with LPS mitogen . The same dose had no effect on IgM-specific response, whereas the 5 mg/kg treatment caused a statiscally significant reduction of anti-SRBC IgM-specific antibodies (82%) . The aqueous extract of A . tenella (50 mg/kg) increased the life span (from 16 +/- 1 to 25 +/- 1 days) and decreased the number of viable tumor cells (59%) in mice with Ehrlich ascites carcinoma . The present findings are significant for the development of alternative, inexpensive and perhaps even safer strategies for cancer treatment. Antimicrob Agents Chemother, 2003 Sep, 47(9), 2875 - 81 Intracellular expression of Peptide fusions for demonstration of protein essentiality in bacteria; Benson RE et al.; We describe a "protein knockout" technique that can be used to identify essential proteins in bacteria . This technique uses phage display to select peptides that bind specifically to purified target proteins . The peptides are expressed intracellularly and cause inhibition of growth when the protein is essential . In this study, peptides that each specifically bind to one of seven essential proteins were identified by phage display and then expressed as fusions to glutathione S-transferase in Escherichia coli . Expression of peptide fusions directed against E . coli DnaN, LpxA, RpoD, ProRS, SecA, GyrA, and Era each dramatically inhibited cell growth . Under the same conditions, a fusion with a randomized peptide sequence did not inhibit cell growth . In growth-inhibited cells, inhibition could be relieved by concurrent overexpression of the relevant target protein but not by coexpression of an irrelevant protein, indicating that growth inhibition was due to a specific interaction of the expressed peptide with its target . The protein knockout technique can be used to assess the essentiality of genes of unknown function emerging from the sequencing of microbial genomes . This technique can also be used to validate proteins as drug targets, and their corresponding peptides as screening tools, for discovery of new antimicrobial agents. Antimicrob Agents Chemother, 2003 Sep, 47(9), 2868 - 74 Microcin C51 plasmid genes: possible source of horizontal gene transfer; Fomenko DE et al.; Microcin C51 (MccC51) is an antimicrobial nucleotide-heptapeptide produced by a natural Escherichia coli strain . A 5.7-kb fragment of the pC51 plasmid carrying the genes involved in MccC51 production, secretion, and self-immunity was sequenced, and the genes were characterized . The sequence of the MccC51 gene cluster is highly similar to that of the MccC7 gene . Recombinant plasmids carrying different combinations of the mcc genes involved in the MccC51 production or immunity were constructed to characterize their functional roles . The mccA, mccB, mccD, and mccE genes are involved in MccC51 production, while the mccC and mccE genes are responsible for immunity to MccC51 . The mcc gene cluster is flanked by 44-bp direct repeats . Amino acid sequence comparisons allowed us to propose functions for each Mcc polypeptide in MccC51 biosynthesis . Plasmid pUHN containing the cloned mccA, mccB, mccC, and mccE genes, but lacking mccD, directed the synthesis of MccC51p, a substance chemically related to MccC51 . MccC51p exhibited weak antibiotic activity against E . coli and was toxic to the producing cells . The immunity to exogenous MccC51 determined by the mccC and mccE genes did not overcome the toxic action of MccC51p on the producing cells . The G+C content of the MccC51 operon, markedly lower than that of the E . coli genome, and the presence of direct repeats suggest the possibility of horizontal transfer of this gene cluster. J Infect Dis, 2003 Sep 1, 188(5), 643 - 52 Epub 2003 Aug 18. Multistate evaluation of invasive pneumococcal diseases in adults with human immunodeficiency virus infection: serotype and antimicrobial resistance patterns in the United States; Fry AM et al.; Persons with acquired immunodeficiency syndrome (AIDS) have a higher incidence of invasive pneumococcal disease (IPD) than other adults, and many receive long-term trimethoprim-sulfamethoxazole (TMP-SMZ) prophylactic therapy . We used 1998-1999 data from the Active Bacterial Core surveillance of the Emerging Infections Program Network to compare IPD infections between adults aged 18-64 years with human immunodeficiency virus (HIV) infection and other adults . Of 2346 patients with IPD, 416 (18%) had HIV or AIDS (HIV/AIDS) . Certain serotypes (serotypes 6A, 6B, 9N, 9V, 18C, 19A, 19F, and 23F) were more common among patients with HIV/AIDS than in adults with no underlying disease (P<.05, vs . serotype 4), even when TMP-SMZ-nonsusceptible isolates were excluded . HIV/AIDS (adjusted odds ratio {aOR}, 1.93; 95% confidence interval {CI}, 1.44-2.59), immunocompromising conditions other than HIV/AIDS (aOR, 1.56; 95% CI, 1.12-2.18), and black race (aOR, 1.50; 95% CI, 1.20-1.88) were independent risk factors for infection with these serotypes . HIV/AIDS was not an independent risk factor for TMP-SMZ nonsusceptibility . Vulnerability to certain serotypes among adults with HIV/AIDS may have implications in prevention strategies. J Magn Reson, 2003 Sep, 164(1), 104 - 14 Susceptibility corrections in solid-state NMR experiments with oriented membrane samples . Part I: applications; Glaser RW et al.; Chemical shift referencing of solid-state NMR experiments on oriented membranes has to compensate for bulk magnetic susceptibility effects that are associated with the non-spherical sample shape, as described in the accompanying paper {J . Magn . Reson . 164 (2003) 115-127} . The resulting frequency deviations can be on the order of 10 ppm, which is serious for nuclei with a narrow chemical shift anisotropy such as 1H or 13C, and in some cases even 19F . Two referencing schemes are proposed here to compensate for these effects: A flat (0.4 mm) glass container with an isotropic reference molecule dissolved in a thin film of liquid is stacked on top of the oriented membrane sample . Alternatively, the intrinsic proton signal of the hydrated lipid can be used for chemical shift referencing . Further aspects related to magnetic susceptibility are discussed, such as air gaps in susceptibility-matched probeheads, the benefits of shimming, and limitations in the accuracy of orientational constraints . A biological application is illustrated by a series of experiments on the antimicrobial peptide PGLa, aimed at understanding its concentration-dependent membranolytic effect . To address a wide range of molar peptide/lipid ratios between 1:3000 and 1:8, multilayers of hydrated DMPC containing a 19F-labeled peptide were oriented between stacked glass plates . Maintaining an approximately constant amount of peptide gives rise to thick samples (18 plates) at low, and thin samples (3 plates) at high peptide/lipid ratio . Accurate referencing was critical to reveal a small but significant change over 5 ppm in the anisotropic chemical shift of the 19F label on the peptide, indicative of a change in the orientation and/or dynamics of PGLa in the membrane. Br J Dermatol, 2003 Aug, 149(2), 296 - 305 In vitro susceptibility testing of ciclopirox, terbinafine, ketoconazole and itraconazole against dermatophytes and nondermatophytes, and in vitro evaluation of combination antifungal activity; Gupta AK et al.; BACKGROUND: With the development of newer antifungal agents with activity against both yeasts and filamentous fungi, there is an increased need to develop and standardize in vitro assays that will evaluate the activity of antimycotics against filamentous fungi . In vitro analysis of antifungal activity of these agents would also allow for the comparison between different antimycotics, which in turn may clarify the reasons for lack of clinical response or serve as an effective therapy for patients with chronic infection . OBJECTIVES: To determine the in vitro susceptibility of fungal organisms to ciclopirox, terbinafine, ketoconazole and itraconazole and to evaluate the in vitro activity and mode of interaction of ciclopirox in combination with either terbinafine or itraconazole . MATERIALS AND METHODS: In the minimum inhibitory concentration (MIC) study 133 strains were evaluated, including dermatophytes (110 strains; 98 from Trichophyton spp.), Candida spp . (14 strains) and nondermatophyte moulds (nine strains) . In vitro susceptibility testing was conducted in microbroth dilutions based on the National Committee for Clinical Laboratory Standards (NCCLS) M27-A proposed standard . The testing MIC ranges were 0.003-2 microg mL-1 for ciclopirox and terbinafine, and 0.06-32 microg mL-1 for itraconazole and ketoconazole . For inoculum preparation, dermatophytes were grown on Heinz oatmeal cereal agar slants . Inoculum suspensions of dermatophytes were diluted in RPMI 1640 (Sigma-Aldrich) with the desired final concentration being 2-5 x 103 c.f.u . mL-1 . Once inoculated, the microdilution plates were set up according to the NCCLS M27-A method, incubated at 35 degrees C, and read visually following 7 days of incubation . For azole agents, the MIC was the lowest concentration showing 80% growth inhibition; for terbinafine and ciclopirox, the MIC was the lowest concentration showing 100% growth inhibition . In the synergy studies, 29 strains from nondermatophyte species were evaluated using a checkerboard microdilution method . The concentrations tested were: 0 and 0.06-32 microg mL-1 for itraconazole, and 0 and 0.003-4 microg mL-1 for both terbinafine and ciclopirox . Modes of interaction between drugs were classified as synergism, additivism, antagonism or indifference based on fractional inhibitory concentration index values (FIC index) . Synergism was defined as an FIC index of < or = 0.50, additivity as an FIC index of < or = 1.0, and antagonism as an FIC index of > or = 2.0 . The drug combination was interpreted as indifferent if neither of the drugs had any visible effect on the presence of the other drug . RESULTS: In the MIC study, the dermatophyte MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (0.04 +/- 0.02), terbinafine (0.04 +/- 0.23), itraconazole (2.28 +/- 7.42) and ketoconazole (0.83 +/- 1.99) . The yeast MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (0.05 +/- 0.02), terbinafine (1.77 +/- 0.58), itraconazole (0.18 +/- 0.27) and ketoconazole (0.56 +/- 0.60) . The non-dermatophyte fungi MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (1.04 +/- 2.62), terbinafine (1.04 +/- 0.95), itraconazole (17.87 +/- 16.75) and ketoconazole (10.69 +/- 13.09) . In the synergy study, with ciclopirox in combination with terbinafine, mainly a synergistic or additive reaction was observed; there were no cases of antagonism . For ciclopirox in combination with itraconazole, there were some instances of additivism or synergism, with indifference in the majority of instances; there were no cases of antagonism . CONCLUSIONS: In vitro susceptibility testing indicates that ciclopirox may have a broad antimicrobial profile including dermatophytes, yeasts and other nondermatophytes . Terbinafine is extremely potent against dermatophytes . In vitro evaluation of activity of ciclopirox and terbinafine suggests many instances of synergy or additivism; for ciclopirox and itraconazole there may be indifference, synergy or additivism. J Nat Prod, 2003 Aug, 66(8), 1074 - 7 The pterocellins, novel bioactive alkaloids from the marine bryozoan Pterocella vesiculosa; Yao B et al.; Two new alkaloids, pterocellins A and B, have been isolated from the New Zealand marine bryozoan Pterocella vesiculosa . Structural elucidation was achieved through NMR and mass spectral analysis in conjunction with a single-crystal X-ray diffraction study of pterocellin A . The pterocellins possess a novel heterocyclic skeleton and exhibit potent antitumor activity and antimicrobial activity in vitro but only modest activity in the in vivo hollow fiber assay at the National Cancer Institute. J Antibiot (Tokyo), 2003 Jun, 56(6), 539 - 42 Seitomycin: isolation, structure elucidation and biological activity of a new angucycline antibiotic from a terrestrial Streptomycete; Abdelfattah M et al.; A new antibiotic, named seitomycin (1c), and the known microbial metabolite tetrangulol methyl ether (2) were found in the ethyl acetate extract of two terrestrial Streptomyces sp . isolates . The structure of the new antibiotic was elucidated by spectroscopic studies and by comparison of the NMR data with the structurally related hatomarubigin C (1a) and SM-196 B (1b) . Seitomycin (1c) showed moderate antimicrobial and weak phytotoxic activity, similar to tetrangulol methyl ether (2). Nihon Kokyuki Gakkai Zasshi, 2003 Jul, 41(7), 463 - 8 {Three cases of Stenotrophomonas maltophilia pneumonia}; Fujino S et al.; We encountered 3 cases of pneumonia caused by Stenotrophomonas maltophilia between January and June 2001 . S . maltophilia is resistant to broad-spectrum antibiotics including carbapenem . Reported studies indicate that excessive use of broad-spectrum antibiotics may induce resistance in this organism . However, our data showed that there was no clear correlation between the amounts of carbapenems used in our hospital and the isolation of the organism . If broad-spectrum antibiotics are ineffective or even actually worsen a case of pneumonia, S . maltophilia may be the sole causative organism, and a potent double- (or triple-) combination therapy consisting of minocyclin and one or two other potent antimicrobial agents should be considered. Leukemia, 2003 Nov, 17(11), 2168 - 77 Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen; Mohty M et al.; In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined . In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days) . The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count . In all, 65% of the bacteremia (95% CI 49-81%) were gram negative . The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days . In multivariate analysis, stem cell source (bone marrow; P=0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (>2 mg/kg) represented the major risk factor for bacteremia (P=0.0001) . Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause . Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT. Oral Microbiol Immunol, 2003 Oct, 18(5), 313 - 7 Virulence factors of Porphyromonas gingivalis are modified by polyphenol oxidase and asparaginase; Budu CE et al.; Porphyromonas gingivalis is a well-adapted pathogen of the periodontal pocket distinguished by its wide array of proteolytic activities and its ability to adhere to multiple substrata in the oral cavity . Microbial proteins with binding functions (such as adhesins and enzymes) very often contain critical tyrosine residues, supported by one or more asparagines in the binding cleft . This study investigates the reduction in adhesiveness and in proteolytic activity after treating P . gingivalis with the tyrosine- and asparagine-targeting enzymes polyphenol oxidase (PPO) and asparaginase (ASG) . Cysteine protease activity was reduced by pretreatment with both enzymes, while the trypsin-like activity was affected only by PPO . Adhesion to buccal epithelial cells, laminin and fibronectin as well as hemagglutination was reduced by one or both of the enzymes . PPO, but not ASG, reduced the coaggregation of P . gingivalis with Actinomyces naeslundii . Treatment with these enzymes might provide an alternative to traditional antimicrobial strategies. J Am Vet Med Assoc, 2003 Aug 15, 223(4), 486 - 91 Osteomyelitis secondary to trauma involving the proximal end of the radius in horses: five cases (1987-2001); Swinebroad EL et al.; OBJECTIVE: To determine clinical, radiographic, and scintigraphic abnormalities in and treatment and outcome of horses with trauma-induced osteomyelitis of the proximal aspect of the radius . DESIGN: Retrospective study . ANIMALS: 5 horses . PROCEDURE: Data collected from the medical records included signalment; history; horse use; degree of lameness; radiographic, ultrasonographic, and scintigraphic findings; treatment; and outcome . RESULTS: Duration of lameness prior to referral ranged from 14 to 60 days . Mean severity of lameness was grade 3 of 5, and all horses had a single limb affected . All horses had signs of pain during elbow joint manipulation and digital palpation over the lateral aspect of the proximal end of the radius . Radiographic lesions consisted of periosteal proliferation, osteolysis, and subchondral bone lysis . Scintigraphy in 3 horses revealed intense pharmaceutical uptake diffusely involving the proximal end of the radius . Two horses had sepsis of the elbow joint . All horses were treated with antimicrobials long-term; 1 horse was also treated by local perfusion of the radial medullary cavity through an indwelling cannulated screw . At follow-up, all horses had returned to their previous function . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that osteomyelitis of the proximal end of the radius can result from a traumatic injury to the antebrachium . Because lesions may be an extension of septic arthritis, a thorough examination of the wound area and elbow joint is recommended . Prolonged systemic antimicrobial treatment can result in a successful outcome. Ir J Med Sci, 2003 Apr-Jun, 172(2), 81 - 2 Erysipelothrix rhusiopathiae endocarditis: a preventable zoonosis? Boo TW, Hone R, Hurley J. BACKGROUND: Erysipelothrix rhusiopathiae is a bacterium ubiquitous in the environment . It can cause a variety of diseases and the risk of infection is closely related to the level of occupational exposure to infected or colonised animals . AIMS: To discuss the clinical features and treatment of this zoonosis, to increase awareness of this pathogen and to emphasise the need for meticulous attention to hygienic work practices in reducing the risk of infection . METHOD: A case report of a farmer with E . rhusiopathiae endocarditis and the management of the infection . RESULTS: The patient was successfully treated with valve replacement surgery and antimicrobial therapy . CONCLUSIONS: Early identification of this microorganism is essential for appropriate treatment of endocarditis . Greater awareness and safe work practices can help reduce the risk of human infection by this microorganism. J Food Prot, 2003 Aug, 66(8), 1495 - 8 Antimicrobial activity of native chitosan, degraded chitosan, and O-carboxymethylated chitosan; Kim KW et al.; The antimicrobial activity of native chitosan was compared to that of lipase-degraded chitosan . The effects of O-carboxymethylated (O-CM) substitution on native (molecular weight, 120; degree of deacetylation, 84.71%) and lipase-degraded chitosans were also investigated . The antimicrobial activity of native chitosan was more extensive than that of lipase-degraded chitosan; however, lipase-degraded chitosan was still highly effective and more water-soluble . O-CM chitosan derived from degraded chitosan was more effective than O-CM chitosan derived from native chitosan . O-CM substitution enhanced lipase-degraded chitosan's antimicrobial activity without reducing its solubility. J Food Prot, 2003 Aug, 66(8), 1426 - 31 Class 1 and class 2 integrons in poultry carcasses from broiler house and poultry processing environments; Roe MT et al.; Integrons have been identified as major genetic contributors to the dissemination of antimicrobial resistance in bacteria . The objective of this study was to examine the prevalence of integrons in poultry processing at the broiler house and in processing plants . Class 1 and class 2 integrons were found throughout the processing environment . Of the two classes of integrons, class 1 was the most prevalent in all processing areas . The levels of both classes of integrons decreased from the farm to the processing plant . Within the chiller tank in the processing plant, the persistence of these sequences appears to be related to the free chlorine concentration of the chiller tank water . The variable regions of the amplified integrons showed size diversity (from 680 to 2,000 bp), suggesting diversity in types of antibiotic-resistance-coding gene cassettes . The presence of the class 1 and class 2 integrons in the chlorinated chiller tank suggests that these sequences are capable of withstanding this critical step in the reduction of microbial loads on poultry carcasses . The persistence of the integron gene sequences on the farm and throughout processing highlights the stability of these transmissible antibiotic-resistance-coding nucleotide sequences and their potential role as reservoirs of antibiotic-resistance-coding genetic elements within the poultry rearing and processing environments. Burns, 2003 Sep, 29(6), 553 - 5 Inducibility of HBD-2 in acute burns and chronic conditions of the lung; Milner SM et al.; The respiratory tract produces a number of molecules that act in the first line of host defense to protect against pathogenic colonization and tissue invasion . Most of the innate antimicrobial activity can be attributed to airway fluid proteins, such as lysozyme, lactoferrin, and secretory leukoproteinase inhibitor, and peptides, such as defensins . Human beta-defensins are cationic antimicrobial peptides with broad and potent microbicidal activity that have been shown to play a role in protecting the healthy lung from infection . To determine the effect of thermal injury on the production of the inducible beta-defensin, human beta-defensin-2 (HBD-2), we measured the concentration of HBD-2 by Western blot analysis in bronchoalveolar lavage samples from the lungs of burned patients with and without inhalation injury . Our data demonstrates an increased amount of HBD-2 in the pulmonary airways with thermal injury compared to normal lung . A further substantial increase in levels was noted in chronic lung conditions. Int J Antimicrob Agents, 2003 Aug, 22(2), 100 - 5 Antibiotic prescribing for adults and children in Israeli emergency rooms; Raz R et al.; The emergency room (ER) is an important focal point for the initiation of antimicrobial therapy but there are few data on antimicrobial prescribing in the ER . The objective of the study was to describe antimicrobial prescribing in Israeli ERs and to compare patterns of prescribing between four different ERs in Northern Israel . The medical records of all patients who attended the ERs during February 2001 were examined . Those patients who were discharged home with a prescription for an antibiotic formed the sample . Paediatric data were only available for two of the four ERs . A total of 970 adults and 470 children attended the four ERs during 1 month and were discharged home with an antibiotic prescription representing 14.6 and 19.9%, respectively, of the total number of patients who visited the ERs . The most common diagnosis leading to an antibiotic prescription was respiratory tract infections (64 in adults and 90% in children) . In adults, cefuroxime-axetil and amoxycillin-clavulanate (both second-line antibiotics) were the most frequently prescribed antibiotics, together accounting for 50% of all antibiotic prescriptions, while in children amoxycillin-clavulanate was favoured (58.9%) . 'Viral infections' accounted for 22.5% of all prescriptions in adults, but only 2.3% in children . Otitis media accounted for almost half of all prescriptions in children . For some diagnoses, such as pneumonia in adults and tonsillitis in children, there was uniformity of prescribing among the different ERs, while for other diagnoses, there were large discrepancies . The ER represents an important source of inappropriate antibiotic prescribing, and measures to curb inappropriate prescribing are urgently needed. Int J Antimicrob Agents, 2003 Aug, 22(2), 89 - 99 Hyperlipidaemia in patients with HIV-1 infection receiving highly active antiretroviral therapy: epidemiology, pathogenesis, clinical course and management; Calza L et al.; A wide range of abnormalities of lipid metabolism have been recently described in HIV-infected patients receiving a protease inhibitor (PI)-based highly active antiretroviral therapy, including hypertriglyceridaemia and hypercholesterolaemia . The increase of plasma lipid concentrations may involve up to 70-80% of HIV-positive subjects treated with a PI-containing regimen and are frequently (but not always) associated with the fat redistribution or the lipodystrophy syndrome . Multiple pathogenetic mechanisms by which antiretroviral agents lead to dyslipidaemia have been hypothesized, but they are still controversial . The potential clinicopathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations report an increased risk of premature coronary artery diseases in young HIV-positive individuals receiving PIs, besides peripheral atherosclerosis and acute pancreatitis . A limited-to-significant improvement of increased triglyceride and cholesterol plasma levels was described in patients who replaced PIs with nevirapine, efavirenz or abacavir, but the risks of long-term toxicity and virological relapse of this treatment switching are not completely defined . A hypolipidaemic diet and regular physical exercise may act favorably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or persists for a long time . The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance . Statins are considered the first-line therapy for the PI-related hypercholesterolaemia, while fibrates are the cornerstone of drug therapy when predominant hypertriglyceridaemia is of concern. Biochem J, 2003 Dec 1, 376(Pt 2), 481 - 7 A novel antimicrobial protein isolated from potato (Solanum tuberosum) shares homology with an acid phosphatase; Feng J et al.; The nucleotide and amino acids sequences for AP(1) will appear in the GenBank(R) and NCBI databases under accession number AY297449 . A novel antimicrobial protein (AP(1)) was purified from leaves of the potato ( Solanum tuberosum, variety MS-42.3) with a procedure involving ammonium sulphate fractionation, molecular sieve chromatography with Sephacryl S-200 and hydrophobic chromatography with Butyl-Sepharose using a FPLC system . The inhibition spectrum investigation showed that AP(1) had good inhibition activity against five different strains of Ralstonia solanacearum from potato or other crops, and two fungal pathogens, Rhizoctonia solani and Alternaria solani from potato . The full-length cDNA encoding AP(1) has been successfully cloned by screening a cDNA expression library of potato with an anti-AP(1) antibody and RACE (rapid amplification of cDNA ends) PCR . Determination of the nucleotide sequences revealed the presence of an open reading frame encoding 343 amino acids . At the C-terminus of AP(1) there is an ATP-binding domain, and the N-terminus exhibits 58% identity with an/the acid phosphatase from Mesorhizobium loti . SDS/PAGE and Western blotting analysis suggested that the AP(1) gene can be successfully expressed in Escherichia coli and recognized by an antibody against AP(1) . Also the expressed protein showed an inhibition activity the same as original AP(1) protein isolated from potato . We suggest that AP(1) most likely belongs to a new group of proteins with antimicrobial characteristics in vitro and functions in relation to phosphorylation and energy metabolism of plants. Am J Clin Dermatol, 2003, 4(9), 597 - 608 Optimal treatment of pyoderma gangrenosum; Gettler S et al.; The optimal treatment of pyoderma gangrenosum includes a combination of local wound care and systemic medications . Oral and pulse intravenous corticosteroids have traditionally been the most commonly recommended first-line systemic therapies . Cyclosporine, with or without corticosteroids, has more recently emerged as a first-line systemic treatment . A multitude of immunosuppressive and immune-modulating medications, as well as antimicrobial agents with anti-inflammatory properties have also been widely prescribed . Often, it is difficult to achieve control of aggressive cases of pyoderma gangrenosum, necessitating administration of a combination of systemic therapies . Furthermore, patients recalcitrant to one or many medications are frequently reported . Concomitant disease, intolerance to a class of medications, and the patient's response to prior therapies can help guide a practitioner in choosing the optimal treatment of pyoderma gangrenosum. Clin Microbiol Infect, 2003 Jul, 9(7), 605 - 13 Plasma secretory leukocyte protease inhibitor in febrile patients; Duits LA et al.; OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) forms an integral part of the lung's defence, by its antimicrobial activity and by its ability to neutralize serine proteases that are released by granulocytes into the inflammatory exudate . Here, we investigate in febrile patients admitted to hospital whether plasma SLPI can serve as a marker of lung infection . METHODS: We prospectively determined the SLPI concentration in 152 febrile patients (median 73 {inter-quantile range (IQR): 58-82} year; 50% male) admitted to hospital because of infection of the airways (n = 44) or pneumonia (n = 108; i.e . consolidation on chest X-ray), and in 48 febrile patients (78 {IQR: 71-85} year; 52% male) admitted because of pyelonephritis, as well as afebrile age-matched controls (n = 38) . In addition, erythrocyte sedimentation rate (ESR), peripheral blood leukocytes, plasma TNFalpha and IL-10, and parameters of the APACHE-II score were determined on admission . RESULTS: In febrile patients, SLPI was significantly increased (P < 0.001) compared with afebrile controls (63 {IQR: 50-76} ng/mL): plasma SLPI (113 {IQR: 83-176} ng/mL) was highest (P < 0.005) in patients with pneumonia compared with other groups (88 {IQR: 70-118} ng/mL) . Only in patients with pneumonia, bacteremia significantly increased (P < 0.01) SLPI concentrations . Using a radiological classification of pulmonary infiltrates based on their size, it was found that plasma SLPI was proportional to the extent of lung tissue involved: the median concentration increased from 95 {IQR: 74-139} ng/mL in unilateral segmental consolidation up to 271 {IQR: 180-460} ng/mL in bilateral lobar consolidations . In a multivariate analysis, the association between SLPI and extent of consolidation was about two-fold stronger than, and independent of, the association between SLPI and erythrocyte sedimentation rate, TNFalpha, and parameters of the composite APACHE-II score, such as heart rate and blood pressure, that reflect severity of illness . CONCLUSION: SLPI is an indicator of the presence and extent of pneumonia in febrile patients admitted to hospital . In patients with an infection with its primary source located outside the lung, plasma SLPI likely reflects the mucosal response to circulating inflammatory mediators reflecting severity of illness. Clin Microbiol Infect, 2003 Jul, 9(7), 600 - 4 Antibiotic resistance of Helicobacter pylori: a cross-sectional study in consecutive patients, and relation to ethnicity; Loffeld RJ et al.; OBJECTIVES: To assess primary antibiotic resistance in a given population and relate the results to ethnicity . MATERIALS AND METHODS: Consecutive cultures were tested for antibiotic susceptibility with the Etest . Three populations were studied separately: ethnic Dutch people, patients of Turkish descent, and patients originating from Africa and the Middle East . RESULTS: Over a period of 5.5 years, 976 (32%) biopsy specimens from 3010 patients were positive for Helicobacter pylori . Metronidazole and clarithromycin resistance were present in 25.8% and 4.8% of the strains, respectively . The number of metronidazole-resistant strains showed a gradual decrease, while clarithromycin resistance showed a slight increase during the study period . Antimicrobial resistance in patients of Turkish descent and in those originating from Africa or the Middle East was significantly higher than in ethnic Dutch people, 35% and 9.1% versus 21% and 2.9%, respectively (P = 0.003 and P = 0.002) . CONCLUSION: It is important to take ethnicity into account when studying antibiotic resistance . The numbers of metronidazole- and clarithromycin-resistant strains can vary considerably between people of different ethnic origin living in the same region. Ceska Slov Farm, 2003 Jul, 52(4), 166 - 70 {Antibiotics in ambulatory practice in Slovakia 1999-2001}; Wawruch M et al.; Evaluation of the consumption of antimicrobial drugs is an important component of antibiotic policy and provides a picture of rationality of treatment . In the present paper, the authors analyzed the consumption of antibacterial agents of the ATC group J01 for systemic use in out-patient practice in Slovakia in 1999-2001 . The data were taken from materials of all Slovak insurance companies provided by the Ministry of Health of the Slovak Republic . The paper evaluated the total out-patient consumption of antimicrobial agents and the financial costs of antibiotic therapy, analyzed the consumption of the individual groups of antibiotics and the consumption of individual agents, and compared the found out-patient consumption with that of Finland . The DDD values in the period under study gave evidence of a high but stable consumption of antibiotics . The analysis according to the groups of antibiotics revealed the dominance of penicillins with wider spectra, penicillins sensitive to beta-lactamases, and macrolides . The evaluation of individual antimicrobial agents showed a positive tendency of the growth of amoxicillin consumption, compensated by a decrease in the consumption of less advantageous ampicillin . The comparison of the Slovak and Finnish consumptions of macrolide antibiotics showed a prevailing consumption of roxitromycin and klaritromycin in Slovakia, and azitromycin in Finland . As far as cephalosporins are concerned, the preparations of the first generation dominated in Finland, and those of the second generation in Slovakia. Intensive Care Med, 2003 Oct, 29(10), 1710 - 6 Epub 2003 Aug 16. A prospective randomized trial of enteral glutamine in critical illness; Hall JC et al.; OBJECTIVE: To assess the influence of enteral glutamine on the incidence of severe sepsis and death in critically ill patients . DESIGN:This two-armed clinical trial was triple blind (patients, attending staff, research nurse) . SETTING: The 10 bed general ICU at Royal Perth Hospital, Western Australia . PATIENTS: This trial evaluated 363 patients requiring mechanical ventilation (median APACHE II score=14); of these, 85 had trauma . INTERVENTION: The intervention solution contained 20 g/l glutamine and the control solution was isojoulic and isonitrogenous . MEASUREMENTS AND RESULTS: The groups had similar characteristics at baseline, and they also received equivalent amounts of protein and energy . Patients in the glutamine group received a median of 19 g/glutamine per day and 91% (332 of 363) of the patients were fed via a nasogastric tube (median duration=10 days) . The outcomes were similar in the two groups: (a) death within 6 months: glutamine group 15% (27 of 179) vs control group 16% (30 of 184); p=0.75; relative risk, 0.95 (95% confidence interval, 0.71-1.28); and (b) severe sepsis: glutamine group 21% (38 of 179) vs control group 23% (43 of 184); p=0.62; relative risk, 0.94 (95% confidence interval, 0.72-1.22) . There was also no discernable difference in the secondary outcomes relating to infections, febrile period, antimicrobial therapy, and consumption of inotropes . CONCLUSION: This clinical trial did not support the use of enteral glutamine supplements in similar cohorts of critically ill patients. Sci Total Environ, 2003 Sep 1, 313(1-3), 245 - 58 Humus quality after eucalypt reforestations in Asturias (Northern Spain); Cristina Zancada M et al.; The impact on soil properties of recent and ancient reforestations with Eucalyptus globulus Labill . has been studied in Cambisols and Leptosols under temperate semi-oceanic climate in Asturias (Northern Spain) . Eucalypt forests showed a high potential of C accumulation in soil, mainly the ancient forest, where the organic matter concentration in the uppermost horizon (up to 415 C g x kg(-1)) was greater than in all neighbouring soil formations (climacic oak forests, up to 84 C g x kg(-1); Podsol under reforested pine forests, 287 C g x kg(-1); and Ulex shrub, 70 C g x kg(-1)) . Nevertheless, there was a low concentration of available bases and a very low transformation degree of the organic matter in this eucalypt forest, only comparable to that of the Podsol . In order to analyse the major features of the biogeochemical behaviour of the sites under study, the humus fractions were isolated and the humic acid fraction was studied by derivative visible and infrared spectroscopies . Incubation experiments on whole soil samples were carried out to monitor stability against biodegradation of the organic matter under comparable conditions . In general, soils under eucalypt had a CO(2) production similar to or lower than the control sites, but the soil under the ancient eucalypt forest had a high potential for CO(2) release, similar to that of the neighbouring Podsol, what might be explained by the presence in these soils of high amounts of C accumulated in readily biodegradable forms . However, the mineralisation coefficients (CO(2) released per unit of soil C) indicated that the biodegradability of the soil humus has decreased significantly in the eucalypt-reforested sites, as it could correspond to an effective control of the biogeochemical processes caused by the antimicrobial products from the eucalypt litter . Compared to the original deciduous forests, the lower values of the E(4)/E(6) ratio in the humic acids from eucalypt forests and the lignin signature in the infrared spectra point to humification mechanisms based on the selective preservation of complex macromolecular substances derived from vascular plants . The second derivative of the visible spectra of the humic acid samples under study showed conspicuous valleys, which are ascribed to fungal-derived 4,9-dihydroxyperylene-3,10-quinone pigments . These valleys were in most eucalypt forests significantly shallower than in the original deciduous forests and may also represent an indicator of the impact of introduced vegetation on the structure of the soil microbial system and the mechanisms responsible for the formation of humic acids. Ann Pharmacother, 2003 Sep, 37(9), 1325 - 8 Effect of tenofovir on didanosine absorption in patients with HIV; Pecora Fulco P et al.; OBJECTIVE: To evaluate the pharmacokinetic interaction between tenofovir and didanosine when used in combination as a highly active antiretroviral therapy regimen . DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966-January 2003) using the terms tenofovir and didanosine . Abstracts from recent meetings, including the International AIDS Society, Interscience Conference on Antimicrobial Agents and Chemotherapy, and the Infectious Diseases Society of America, were reviewed for relevant abstracts and poster presentations . DATA SYNTHESIS: Pharmacokinetic studies evaluating the concurrent use of tenofovir and didanosine have been performed in healthy volunteers . Tenofovir 300 mg administered concurrently with 400 mg didanosine results in a 48-64% increase in the didanosine maximum plasma concentration and AUC with no significant alterations in the tenofovir pharmacokinetic parameters . Tenofovir 300 mg and didanosine 250 mg has been compared with didanosine 400 mg alone . The results demonstrated equivalent didanosine AUCs . CONCLUSIONS: When used concurrently, tenofovir significantly increases the maximum plasma concentration and the AUC of didanosine . Additional data in HIV-infected patients are needed to determine the long-term toxicities of this combination therapy . Didanosine dose reduction should be considered when these 2 agents are used concurrently. Biomol Eng, 2003 Jul, 20(4-6), 421 - 3 Phylogenetic identification of bacteria with antimicrobial activities isolated from Mediterranean sponges; Thiel V et al.; Bacteria were isolated from Mediterranean sponges and specifically selected according to their antimicrobial activity . They were classified on the basis of partial 16S rDNA sequences as members of distinct clusters of alpha-Proteobacteria and gamma-Proteobacteria . The action spectrum of antimicrobial activities against target organisms was related to the phylogenetic position of the isolates. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2003 Aug, 15(8), 495 - 8 {Comparison of severe acute respiratory syndrome with community-acquired pneumonia}; Xue XY et al.; OBJECTIVE: To study the features of severe acute respiratory syndrome (SARS) and community acquired pneumonia (CAP) . METHODS: The clinical presentation, chest radiographs, white blood cell count and outcome of 45 SARS patients from April 5 to 20 2003 were compared, with those of 80 CAP patients from October 1 2002 to April 1 2003 in our hospital, and the clinical features of SARS were summarized . RESULTS: (1) Fever above 38.5 centigrade, dry cough, short of breath, headache, myalgia, diarrhea in SARS were more common in SARS patients than those in CAP (P<0.01) . (2) Leucopenia was more common and leukocytosis was less common in SARS than those in CAP (P<0.01) . (3) 22.2 percent of SARS patients were found abnormal chest radiographs within 24 hours after onset, 71.1 percent of SARS patients were showed progressive pulmonary infiltration via serial chest radiographs, while all CAP patients had abnormal chest radiographs when they were seen first time, and no patient showed progressive pulmonary infiltration, the difference was significant between the two groups (P<0.01) . (4) Patients with SARS were lack of a response to the initial antimicrobial therapy, all patients with CAP had an adequate clinical response within three days, the difference was significant between the two groups(P<0.01 ) . (5) The ratio of severe pneumonia and mortality in SARS was much higher than in CAP (both P<0.01) . CONCLUSION: The clinical presentation, chest radiographs, white blood cell count, response to initial antimicrobial therapy, and outcome in SARS is much different from CAP, differentiate them will be helpful to early recognition, prompt isolation, and prevention of its spread. Br J Clin Pharmacol, 2003 Sep, 56(3), 273 - 83 Diagnostic methods for Helicobacter pylori detection and eradication; Goddard AF et al.; Helicobacter pylori is the principal cause of peptic ulcer disease and an important risk factor for the development of gastric cancer . The efficacy of 1 week triple therapies, which often have eradication rates of>90%, is undermined by poor patient compliance and bacterial antimicrobial resistance . The development of new anti-H . pylori therapies presents enormous challenges to clinical pharmacologists, not only in the identification of novel targets, but also in ensuring adequate drug delivery to the unique gastric mucus niche of H . pylori . Animal models of H . pylori infection have been developed but their clinical validity has yet to be established . Vaccination, to prevent or treat infection, has been demonstrated in animal models, but human studies have not been so encouraging. Boll Chim Farm, 2003 May, 142(4), 167 - 74 Synthesis of novel pyrimidine-2,4-diones and 2-thioxo-pyrimidine-4-ones as potential anticancer and antimicrobial agents; Soliman R et al.; Two novel series of pyrimidine derivatives have been prepared, namely; 3,6-disubstituted perhydropyrimidine-2,4-diones 8a-l as well as 3,6-disubstituted 2-thioxo-perhydropyrimidine-4-ones 9a-k . The anticancer as well antimicrobial activities of these compounds and their open-chain counterparts have been determined. Arzneimittelforschung, 2003, 53(7), 522 - 5 Synthesis and antimicrobial activity of flavone-3'-carboxaldehyde oxime ether derivatives; Bozdag-Dundar O et al.; A new series of flavonyl oxime ether derivatives (FO1-FO6) was prepared by reaction of flavone-3'-carboxaldehyde (III) with O-substituted hydroxyl amine derivatives (IV) . The synthesized compounds were tested for their in vitro antifungal and antibacterial activities . All the compounds exhibited antimicrobial activity. Biochem J, 2003 Nov 1, 375(Pt 3), 737 - 44 Amoebapores and NK-lysin, members of a class of structurally distinct antimicrobial and cytolytic peptides from protozoa and mammals: a comparative functional analysis; Bruhn H et al.; Amoebapores, the pore-forming polypeptides of the protozoan parasite Entamoeba histolytica, and NK-lysin, an effector molecule of porcine NK (natural killer) and cytotoxic T cells, belong to the same protein family, the saposin-like proteins . As both types of protein are implicated in the killing of microbes in vivo, it appears that phylogenetically diverse organisms such as amoebae and mammals use similar effector molecules to fulfil a comparable task . However, structural features have led to the assumption that the proteins display their activities according to different modes of action . To address this question, we analysed the antibacterial, cytotoxic and pore-forming activities of these proteins in parallel and in comprehensive detail . Interestingly, the comparison of activities revealed significant differences . Whereas NK-lysin, recombinantly expressed, is efficient at a broad range of pH values, the amoebapores exhibited a pronounced pH dependence of all their activities, with markedly decreased activity at pH values above 6 . Moreover, increasing salinity affects amoebapores more drastically than NK-lysin . All of the proteins compared were found to be potently active against Gram-positive bacteria, but only NK-lysin was equally efficient against Gram-negative bacteria . However, the amoebapores displayed five times higher pore-forming activity than NK-lysin, which is in accordance with the more hydrophobic character of the amoebapores compared with the essentially cationic NK-lysin. AAPS PharmSciTech . 2002;3(3):E20. Mucoadhesive vaginal tablets as veterinary delivery system for the controlled release of an antimicrobial drug, acriflavine; Gavini E et al.; The aim of the study was the development of mucoadhesive vaginal tablets designed for the local controlled release of acriflavine, an antimicrobial drug used as a model . The tablets were prepared using drug-loaded chitosan microspheres and additional excipients (methylcellulose, sodium alginate, sodium carboxymethylcellulose, or Carbopol 974) . The microspheres were prepared by a spray-drying method, using the drug to polymer weight ratios 1:1 and 1:2 and were characterized in terms of morphology, encapsulation efficiency, and in vitro release behavior, as MIC (Minimum Inhibitory Concentration), MBC (Minimum Bacterial Concentration), and killing time (KT) . The tablets were prepared by direct compression, characterized by in vitro drug release and in vitro mucoadhesive tests . The microparticles have sizes of 4 to 12 microm; the mean encapsulation yields are about 90% . Acriflavine, encapsulated into the polymer, maintains its antibacterial activity; killing time of the encapsulated drug is similar to that of the free drug . In vitro release profiles of tablets show differences depending on the excipient used . In particular Carbopol 974, which is highly cross-linked, is able to determine a drug-controlled release from the matrix tablets for more than 8 hours . The in vitro adhesion tests, carried out on the same formulation, show a good adhesive behavior . The formulation containing microspheres with drug to polymer weight ratios of 1:1 and Carbopol 974 is characterized by the best release behavior and shows good mucoadhesive properties . These preliminary data indicate that this formulation can be proposed as a mucoadhesive vaginal delivery system for the controlled release of acriflavine. Int J Food Microbiol, 2003 Sep 15, 86(3), 223 - 30 Thermal resistances and lactate and diacetate sensitivities of bacteria causing bologna discolouration; Peirson MD et al.; This report describes the effects of heat, sodium lactate, and sodium diacetate on the viabilities of Weissella viridescens ATCC 12706, Aerococcus viridans MPL-1 and MPL-B, and Carnobacterium viridans ATCC BAA 336 . The latter three organisms were isolated from commercial product and have previously been shown to produce green discolourations in cooked cured bologna . W . viridescens was heat resistant in beef bologna (D(60 degrees C)=14.7 min) but not in APT broth . A . viridans and C . viridans were much more sensitive to heat (D(60 degrees C) in beef bologna < or =1.3 min), indicating that these organisms were probably post-pasteurization contaminants . Sodium lactate (3.0%) alone or in combination with 0.3% sodium diacetate slowed the growth rate and reduced the final cell numbers of A . viridans and C . viridans in inoculated bologna . W . viridescens was only slightly affected by the combined antimicrobials . The combination of sodium lactate and sodium diacetate prevented A . viridans and C . viridans from affecting the colour of beef bologna . However, lactate and diacetate themselves reduced red colour, as measured by HunterLab colourimetry . HunterLab a values for fresh beef bologna were 13.4 (no antimicrobial added), 9.6 (3.0% sodium lactate), 8.0 (0.3% sodium diacetate), and 7.9 (3.0% sodium lactate + 0.3% sodium diacetate). Arch Pediatr, 2003 Jun, 10(6), 521 - 3 {Acute immune epiduritis in a child}; Boumpoutou R et al.; Acute epiduritis is an uncommon disease especially in children . We report an unusual case of acute epiduritis in a child, revealed by characteristic clinical signs and Magnetic Resonance Imaging (MRI) . Given the absence of identified infectious or tumoral cause, and the ineffectiveness of antimicrobial treatment, a therapeutic test with polyvalent immunoglobulins was implemented . Rapid clinical improvement led to the retrospective diagnosis of probable immunological acute epiduritis. Acta Chir Belg, 2003 Jun, 103(3), 241 - 7 The role of iodine in antisepsis and wound management: a reappraisal; Selvaggi G et al.; For more than 150 years, iodine has been used for the prevention of infection and for the treatment of wounds . Nowadays a large amount of published evidence is available and, although it is generally in support of the use of iodine product, it is confused by being a mixture of laboratory, animals and human studies, often using different preparations . This makes interpretation and comparison difficult . After new developments and publications, the role of iodine in antisepsis and in wound management needs to be reevaluated . We mainly focused our review on the following problems: the role of the newly developed formulations of iodine preparations, its antimicrobial activity, the possibility of impairing the wound healing process, the role of iodine in the problem of growing resistance against antibiotics and antiseptics . New formulations seem to keep the same clinical efficacy, avoiding the problem of toxicity; it seems that the antibacterial activity of iodine is superior compared to other products and, in contrast with antibiotics and other antiseptics, it seems to have no resistance problem . It seems that povidone-iodine has all the characteristics to become the first choice antiseptic in wound treatment. J Rheumatol, 2003 Aug, 30(8), 1719 - 24 Intraarticular release and accumulation of defensins and bactericidal/permeability-increasing protein in patients with rheumatoid arthritis; Bokarewa MI et al.; OBJECTIVE: Defensins and bactericidal/permeability-increasing protein (BPI) are the components of the azurophilic granules of polymorphonuclear cells (PMNC) maintaining antimicrobial protection . Both these substances have been suggested to interact with the host immune system rather than merely kill invading pathogens . We assessed concentrations of BPI and a-defensins in synovial fluid (SF) and matching blood samples of patients with rheumatoid arthritis (RA) . METHODS: Matching samples of SF and blood were collected from 67 patients with RA (aged 21-73 yrs) with acute joint effusion . Blood samples from 22 healthy individuals made up a control group . Concentrations of BPI and human neutrophil peptides (HNP 1-3) were measured by ELISA . The results were related to radiological signs of destructive arthritis, duration of the disease, and laboratory markers of inflammation . RESULTS: BPI and HNP concentrations in SF were 10-60 times higher than in matching blood samples (p < 0.0001) . Strong correlations between BPI and HNP concentrations were found in both blood and SF . In SF, BPI and HNP concentrations correlated to white blood cell (WBC) count (p < 0.001), and were associated with erosive joint disease (p < 0.05) . In contrast, WBC count, serum C-reactive protein, or rheumatoid factor were not significantly correlated to the BPI or HNP concentrations . Serum BPI concentrations were moderately but significantly increased in RA patients compared in blood to controls (p < 0.05) . CONCLUSION: BPI and HNP are accumulated in the synovial cavity of patients with RA . Significant correlation between joint erosion and local occurrence of BPI and HNP suggests participation of these molecules in regulation of the destructive course of RA. Clin Cancer Res, 2003 Aug 1, 9(8), 3176 - 82 Activation of prodeath Bcl-2 family proteins and mitochondrial apoptosis pathway by sanguinarine in immortalized human HaCaT keratinocytes; Adhami VM et al.; Sanguinarine, derived from the root of Sanguinaria canadensis and other poppy fumaria species, possesses strong antimicrobial, anti-inflammatory, and antioxidant properties . We earlier showed that sanguinarine kills human epidermoid carcinoma A431 cells via an induction of apoptosis {N . Ahmad et al., Clin . Cancer Res., 6: 1524-1528, 2000} . In this study, using immortalized human keratinocytes (HaCaT cells), we provide information about mechanism of the antiproliferative effect of sanguinarine . Sanguinarine {0.1 (M-2 (M)} treatment to HaCaT cells was found to inhibit in a dose-dependent manner the cell proliferation and induce apoptosis, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA, respectively . Sanguinarine treatment also resulted in a significant cleavage of poly(ADP-ribose) polymerase in HaCaT cells . Because mitochondrial pathway is critical for the regulation of apoptosis, we studied the involvement and regulation of mitochondrial events in sanguinarine-mediated apoptosis of HaCaT cells . As shown by the immunoblot analysis, our data clearly demonstrated that sanguinarine treatment to HaCaT cells resulted in a dose-dependent (a) increase in the level of Bax with a concomitant decrease in Bcl-2 levels and (b) increase in Bax/Bcl-2 ratio . Sanguinarine also resulted in significant increases in the proapoptotic members of Bcl-2 family proteins, i.e., Bak and Bid . This was accompanied by increase in (a) protein expression of cytochrome c and apoptotic protease-activating factor-1 and (b) activity and protein expression of caspase-3, caspase-7, caspase-8, and caspase-9 . Taken together, our data showed the involvement of mitochondrial pathway and Bcl-2 family proteins during sanguinarine-mediated apoptosis of immortalized keratinocytes . We suggest that sanguinarine could be developed as a drug for the management of hyperproliferative skin disorders, including skin cancer. BMC Gastroenterol . 2003 Aug 11;3(1):20. Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates; Godoy AP et al.; BACKGROUND: In this study, we evaluated the prevalence of primary resistance of Brazilian H . pylori isolates to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone . In addition, the vacA, iceA, cagA and cagE genotypes of strains isolated from Brazilian patients were determined and associated with clinical data in an effort to correlate these four virulence markers and antibiotic resistance . METHODS: H . pylori was cultured in 155 H . pylori-positive patients and MICs for metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone were determined by the agar dilution method . Genomic DNA was extracted, and allelic variants of vacA, iceA, cagA and cagE were identified by the polymerase chain reaction . RESULTS: There was a strong association between the vacA s1/cagA -positive genotype and peptic ulcer disease (OR = 5.42, 95% CI 2.6-11.3, p = 0.0006) . Additionally, infection by more virulent strains may protect against GERD, since logistic regression showed a negative association between the more virulent strain, vacA s1/cagA-positive genotype and GERD (OR = 0.26, 95% CI 0.08-0.8, p = 0.03) . Resistance to metronidazole was detected in 75 patients (55%), to amoxicillin in 54 individuals (38%), to clarithromycin in 23 patients (16%), to tetracycline in 13 patients (9%), and to furazolidone in 19 individuals (13%) . No significant correlation between pathogenicity and resistance or susceptibility was detected when MIC values for each antibiotic were compared with different vacA, iceA, cagA and cagE genotypes . CONCLUSION: The analysis of virulence genes revealed a specific association between H . pylori strains and clinical outcome, furthermore, no significant association was detected among pathogenicity and resistance or susceptibility. Vet Clin North Am Small Anim Pract, 2003 Jul, 33(4), 773 - 89 Feline hemotropic mycoplasmosis (feline hemobartonellosis); Sykes JE; Hemotropic mycoplasmas represent an important cause of anemia in cats worldwide . Previously known as Haemobartonella species, sequencing of the 16S rRNA genes of these organisms has led to their reclassification as mycoplasmas . Two species have been identified in cats, M haemofelis and "Candidatus M haemominutum." The latter organism alone has not been associated with disease in naturally infected cats but may cause anemia in FeLV-infected cats and accelerate development of FeLV-induced myeloproliferative disease . The mode of transmission of these organisms remains enigmatic . Nevertheless, development of sensitive DNA-based tests for these unculturable organisms has improved the understanding of the epidemiology and pathogenesis of FHM . Cats with clinical signs and laboratory abnormalities consistent with FHM should be treated with doxycycline; enrofloxacin may represent an effective alternative . Transfusion with packed red blood cells after cross-matching may be required for severely anemia cats, and addition of prednisone may be required if the diagnosis of FHM is uncertain, or response to antimicrobials alone is insufficient . Affected cats should be tested for FeLV, the most common concurrent infection in cats with FHM. Proteins, 2003 Sep 1, 52(4), 534 - 43 A left-handed alpha-helix containing both L- and D-amino acids: the solution structure of the antimicrobial lipodepsipeptide tolaasin; Jourdan F et al.; The 18-amino acid cytolytic lipodepsipeptide tolaasin, produced in culture by virulent strains of Pseudomonas tolaasii, is the causal agent of the brown blotch disease of the cultivated mushroom . Tolaasin has a sequence of D-amino acids in its N-terminal region, then alternates L- and D-amino acids, and bears a C-terminal lactone macrocycle composed of 5-residues . The solution structure of tolaasin in sodium dodecyl sulfate was studied by 2D-NMR spectroscopy and molecular dynamics simulated annealing calculations . Tolaasin forms an amphipathic left-handed alpha-helix in the regionDPro2-DalloThr14 comprising the sequence of seven D-amino acids and the adjacent L-D-L-D-D-region . To the best of our knowledge, this is the first recognized example of a left-handed alpha-helix including both D- and L-amino acids . The lactone macrocycle adopts a "boat-like" conformation and is shifted from the helical axis as to form a "golf-club" overall conformation . These structural features will be of importance in understanding, and preventing, tolaasin's role in the bacterial colonization of the host plant, and its toxic action on cells . Furthermore, the observed antimicrobial activity together with the potential resistance to enzymatic degradation and the increased antigenicity (both due to the presence of L- and D-amino acids) strongly suggests for tolaasin a potential role as a template model for the design of new therapeutic antibacterial molecules . Med Dosw Mikrobiol, 2003, 55(1), 89 - 96 {Use of impedance test for testing effectiveness of drug preservatives}; Zareba T et al.; Pharmacopoeias contain preservation efficacy test for estimating antimicrobial activity of chemical compounds added to pharmaceutical preparations in multidose containers in order to inhibit bioburden growth . This method involves the treating of preserved products with bacteria and yeast cells and monitoring the survival of microorganisms through the specified time periods up to 28 days . The last stage of assay--incubation and colony counting--is very time consuming . Recent advance in technology enables faster and more convenient detection in comparison to traditional methods . Impedance method is based on the principle that conductance and capacitance of cultivation medium increases when bacteria grow and metabolize, Impedance time detection is inversely proportional to initial bacterial population . Six different products were utilised throughout the study . The calibration curves were calculated for each of the tested strains by comparison between standard plate count method and detection time measured in Bactometer system . In our study log reduction calculated in alternative method were similar to those obtained in plate count assay . All of the tested preparations, except one, exhibited acceptable activity against bacteria and fungi and meet the pharmacopoeal requirements . The studies indicated a positive correlation between standard plate count results and impedance reading . The procedure with the usage of Bactometer, provides a rapid and accurate system for the determination of bacterial content. Plant Cell Rep, 2003 Nov, 22(4), 252 - 60 Epub 2003 Aug 08. High-efficiency biolistic co-transformation and regeneration of 'Chardonnay' (Vitis vinifera L.) containing npt-II and antimicrobial peptide genes; Vidal JR et al.; A reliable and efficient system for transformation and regeneration of 'Chardonnay' (Vitis vinifera L.) plants via microprojectile bombardment was developed . Improvements over the previous biolistic transformation system included: (1) the use of gold particles for bombardment; (2) step-wise selection at 10 then 15 mg/l kanamycin; and (3) embryo induction at 27 degrees C . Embryogenic cell cultures were either bombarded with pBI426, which contains the reporter gene gus (uidA) coding for beta-glucuronidase (GUS), or were co-bombarded with pSAN237 carrying the npt-II (neomycin phosphotransferase II) selectable marker gene, and a second plasmid with an antimicrobial peptide gene . A large number of transient (7,883 +/- 1,928) and stable (46 +/- 32) blue spots per plate at 2 and 95 days after bombardment, respectively, were obtained according to GUS expression analyses . A total of 447 putative transgenic embryos was harvested from 84 bombarded plates . From these embryos, 242 (54%) were regenerated into plants within the first year of the experiment . Southern blot analyses confirmed integration of the transgenes into the grape genome . Co-transformation was tested with four separate antimicrobial constructs . The co-transformation frequency of unlinked genes was 48% as measured by polymerase chain reaction (PCR), and 56% as estimated by dot blot hybridization . Expression of the gus gene, and PCR and Southern blot analyses of npt-II and antimicrobial genes from regenerated plants document stable transformation of 'Chardonnay' and establish the parameters for highly-efficient biolistic transformation in V . vinifera. Chest, 2003 Aug, 124(2), 526 - 35 An economic evaluation of sequential i.v./po moxifloxacin therapy compared to i.v./po co-amoxiclav with or without clarithromycin in the treatment of community-acquired pneumonia; Drummond MF et al.; STUDY OBJECTIVE: To evaluate costs, clinical consequences, and cost-effectiveness from a German and French health-care system perspective of sequential i.v./po moxifloxacin monotherapy compared to co-amoxiclav with or without clarithromycin (AMC +/- CLA) in patients with community-acquired pneumonia (CAP) who required parenteral treatment . METHODS: Costs and consequences over 21 days were evaluated based on clinical cure rates 5 to 7 days after treatment and health resource use reported for the TARGET multinational, prospective, randomized, open-label trial . This trial compared sequential i.v./po monotherapy with moxifloxacin (400 mg qd) to i.v./po co-amoxiclav (1.2 g i.v./625 mg po tid) with or without clarithromycin (500 mg bid) for 7 to 14 days in hospitalized patients with CAP . Since no country-by-treatment interaction was found in spite of some country differences for length of hospital stays, resource data (antimicrobial treatment, hospitalization, and out-of-hospital care) from all centers were pooled and valued using German and French unit prices to estimate CAP-related cost to the German Sickness Funds and French public health-care sector, respectively . RESULTS: Compared to AMC +/- CLA, treatment with moxifloxacin resulted in 5.3% more patients achieving clinical cure 5 to 7 days after therapy (95% confidence interval {CI}, 1.2 to 11.8%), increased speed of response (1 day sooner for median time to first return to apyrexia, p = 0.008), and a reduction in hospital stay by 0.81 days (95% CI, - 0.01 to 1.63) within the 21-day time frame . Treatment with moxifloxacin resulted in savings of 266 euro and 381 euro for Germany and France respectively, primarily due to the shorter length of hospital stay . Cost-effectiveness acceptability curves show moxifloxacin has a > or = 95% chance of being cost saving from French and German health-care perspectives, and higher probability of being cost-effective at acceptability thresholds up to 2,000 euro per additional patient cured . CONCLUSION: i.v./po monotherapy with moxifloxacin shows clinical benefits including increased speed of response and is cost-effective compared to i.v./po AMC +/- CLA in the treatment of CAP. J Pharm Biomed Anal, 2003 Aug 21, 32(6), 1167 - 74 LC-MS/MS determination of Synercid injections; Abdel-Hamid ME et al.; Synercid is a combination of two semisynthetic pristinamycin derivatives, quinupristin and dalfopristin in 30:70 (w/w) ratio . A rapid and specific high-performance liquid chromatography-mass spectrometry was developed for the determination of quinupristin and dalfopristin using positive electrospray tandem mass spectrometry (+ESI-MS/MS) . Multiple reaction monitoring transitions at 1023.05>134.34 and 691.87>166.26 were selected for the quantitation of quinupristin and dalfopristin, respectively . The assay run cycle-time was approximately 2.0 min injection-to-injection . The assay was linear up to concentration of 4000 ng x ml(-1) quinupristin and 1920 ng x ml(-1) dalfopristin . The lowest limits of quantitation of quinupristin and dalfopristin were found to be 1000 and 480 ng x ml(-1), respectively . Quantitation was based on peak area measurement of quinupristin and dalfopristin using weighed linear regression . Linear relationships with correlation coefficients (r>0.99) were automatically computed for both constituents by MASSLYNX quantify program . The ratio of the slopes of the calibration curves of quinupristin and dalfopristin was found to be 0.425, which matches the nominal ratio composition of the antimicrobial compounds in Synercid . The %RSD ranges were 2.3-4.0% for dalfopristin and 1.3-4.2% for quinupristin, whereas the %DEV ranges were (-7.5+3.7) and (-1.2+9.1%), respectively, indicating appropriate precision and accuracy . Recoveries of 99.5-103.8% and 97.8-99.0% of quinupristin and dalfopristin, respectively, were computed from Synercid injection . The described method is recommended for rapid determination of the contents and for tracking the stability and compatibility of quinupristin and dalfopristin in Synercid injection. Mol Ther, 2003 Aug, 8(2), 295 - 305 Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium; Mi Z et al.; Synovial hyperplasia, resulting in erosion of cartilage and bone, represents one of the major pathologies associated with rheumatoid arthritis . To develop an approach for efficient delivery of proteins or agents to synovium to induce targeted apoptosis of hyperplastic synovial tissue, we have screened an M13 peptide phage display library for synovial-specific transduction peptides . We identified a novel synovial-targeted transduction peptide, HAP-1, which is able to facilitate specific internalization of protein complexes into human and rabbit synovial cells in culture and rabbit synovial lining in vivo . HAP-1 and a non-tissue-specific cationic protein transduction domain, PTD-5, were fused to an antimicrobial peptide, (KLAK)(2), to generate two proapoptotic peptides termed DP2 and DP1, respectively . Administration of these peptides was able to induce apoptosis of rabbit and human synovial cells in culture, with DP2 inducing synovial cell-specific apoptosis . Intra-articular injection of DP1 and DP2 into arthritic rabbit joints with synovial hyperplasia induced extensive apoptosis of the hyperplastic synovium, while reducing the leukocytic infiltration and synovitis . These results suggest that proapoptotic peptides and, in particular, DP2 can be clinically useful for treatment of synovial hyperplasia, as well as inflammation . Moreover, the results demonstrate the feasibility of identifying tissue-specific transduction peptides capable of mediating efficient transduction in vivo. Structure (Camb), 2003 Aug, 11(8), 902 - 3 Shikimate dehydrogenase structure reveals novel fold; Vogan E; The structure of shikimate 5-dehydrogenase, the fourth enzyme in the shikimate biosynthesis pathway and a member of a large enzyme family without clear structural peer, reveals a novel topological fold for the substrate binding domain and, through homology modeling, expands the possibilities for antimicrobial and herbicide design. Curr Allergy Asthma Rep, 2003 Sep, 3(5), 402 - 9 Endogenous production of antimicrobial peptides in innate immunity and human disease; Gallo RL et al.; Antimicrobial peptides are diverse and evolutionarily ancient molecules produced by all living organisms . Peptides belonging to the cathelicidin and defensin gene families exhibit an immune strategy as they defend against infection by inhibiting microbial survival, and modify hosts through triggering tissue-specific defense and repair events . A variety of processes have evolved in microbes to evade the action of antimicrobial peptides, including the ability to degrade or inactivate antimicrobial peptides, or suppress host production of the peptide in response to infection . Animal models and clinical investigations have shown that an absence of cathelicidin or defensin antimicrobials can lead to disease . In this article, we review important recent advances in understanding the biology of antimicrobial peptides and their role in normal immunity and human disease. Curr Allergy Asthma Rep, 2003 Sep, 3(5), 396 - 401 Immune deficiencies due to defects in cytokine signaling; Kelly J et al.; Severe combined immunodeficiency (SCID) represents a syndrome comprising the most severe forms of inherited immunodeficiencies . Defects in cytokine signaling pathways can result in impaired development of lymphoid cells and/or defective functioning of these cells, and most cases of SCID result from defective signaling through the common cytokine receptor g chain (g(c)) or associated molecules and signaling pathways . Studies of these patients and the analysis of gene-targeted mice provide insight into the underlying signaling defects in inherited immunodeficiencies . The identification of the genetic defects in humans with SCID provides the basis for future therapies for these patients . More subtle deficiencies in cytokine signaling have also been found as causes of other forms of immunodeficiency, and the knowledge learned could lead to novel approaches to antimicrobial therapy. Surg Infect (Larchmt), 2003 Summer, 4(2), 219 - 26 Honey in the management of infections; Namias N; BACKGROUND: Honey, a natural product of bees of the genera Apis and Meliponinae, has been recognized for medicinal properties since antiquity . Honey has demonstrated antimicrobial properties . These effects are variably ascribed to the pH, hydrogen peroxide content, osmotic effect, and as yet unidentified compounds putatively described as inhibines . MATERIALS AND METHODS: This review will explore the use of honey in necrotizing soft tissue infections, postsurgical wound infections, wounds other than postsurgical infections, Helicobacter pylori of the stomach and duodenum, and burns . Throughout, the in vitro evidence that exists and the explanations that can be offered for the purported benefits of honey will be reviewed . Most of the reports are either uncontrolled case series or in vitro observations . As such, detailed critique of statistical methods will not be undertaken . CONCLUSION: The purpose of this paper is not to debunk honey therapy as a myth, but to stimulate thought among surgeons interested in surgical infection and perhaps serve as the nidus for future research . The use of honey should be considered when more conventional therapies have failed. Arthritis Rheum, 2003 Aug, 48(8), 2146 - 54 Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis; Cambridge G et al.; OBJECTIVE: To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA) . METHODS: B lymphocyte depletion was attained using combination therapy based on the monoclonal anti-CD20 antibody rituximab . Levels of a serologic indicator of inflammation, C-reactive protein (CRP), of antimicrobial antibodies, of autoantibodies including IgA-, IgM-, and IgG-class rheumatoid factors (RF), and of antibodies to cyclic citrullinated peptide (anti-CCP) were assayed . RESULTS: The majority of patients showed a marked clinical improvement after treatment with rituximab, with benefit lasting up to 33 months . Levels of total serum immunoglobulins fell, although the mean values each remained within the normal range . Whereas the IgM-RF response paralleled the changes in total serum IgM levels, the levels of IgA-RF, IgG-RF, and IgG and anti-CCP antibodies decreased significantly more than did those of their corresponding total serum immunoglobulin classes . The kinetics for the reduction in CRP levels also paralleled the decreases in autoantibody levels . In contrast, levels of antimicrobial antibodies did not change significantly . B lymphocyte return occurred up to 21 months posttreatment . The time to relapse after B lymphocyte return was often long and unpredictable (range 0-17 months) . Relapse was, however, closely correlated with rises in the level of at least one autoantibody . Increased autoantibody levels were rarely observed in the absence of clinical change . CONCLUSION: Following B lymphocyte depletion in patients with RA, a positive clinical response occurred in correlation with a significant drop in the levels of CRP and autoantibodies . Antibacterial antibody levels were relatively well maintained . B lymphocyte return preceded relapse in all patients . There was also a temporal relationship between clinical relapse and rises in autoantibody levels . Although these observations are consistent with a role for B lymphocytes in the pathogenesis of RA, the precise mechanisms involved remain unclear. Clin Infect Dis, 2003 Aug 15, 37(4), 543 - 50 Epub 2003 Jul 30. The epidemiology of burn wound infections: then and now; Mayhall CG; Burn wound infections are a serious complication of thermal injury . Although pneumonia is now the most important infection in patients with burns, burn wound infection remains a serious complication unique to the burn recipient . The methods for managing thermal injury have evolved during the past 50 years . This evolution has been accompanied by changes in the etiology, epidemiology, and approach to prevention of burn wound infections . In the 1950s, 1960s, and 1970s and into the mid-1980s, burn wounds were treated by the exposure method, with application of topical antimicrobials to the burn wound surface and gradual debridement with immersion hydrotherapy . As early burn wound excision and wound closure became the focal point of burn wound management, accompanied by a change from immersion hydrotherapy to showering hydrotherapy, the rate of burn wound infection appeared to decrease . Few epidemiologic studies have been done since this change in the approach to management of thermal injury . There are few data on the epidemiology of burn wound infections from the era of early excision and closure . Data are needed on infection rates for excised and closed burn wounds, the etiologies of these infections, and the epidemiology and the prevention of such infections . Additional studies are needed on the indications for topical and antimicrobial prophylaxis and selective decontamination of the digestive tract. Clin Infect Dis, 2003 Aug 15, 37(4), 498 - 505 Epub 2003 Aug 01. The inventory of antibiotics in Russian home medicine cabinets; Stratchounski LS et al.; The objective of this study was to inventory the stock of antimicrobials in the home medicine cabinets (HMCs) of the general population in Russia and to find out for which indications people report that they would use antibiotics without a physician's recommendation . The research was performed in 9 Russian cities by physicians who visited households . An inventory of antibiotics in HMCs was made, and respondents were asked about instances in which they would choose automedication with antibiotics . We found that 83.6% of families had antibiotics for systemic use in HMCs . The most common antibiotics in HMCs were trimethoprim-sulfamethoxazole (46.3% of HMCs), ampicillin (45.1%), chloramphenicol (32.7%), erythromycin (25.5%), and tetracycline (21.8%) . The major indications for automedication with antibiotics were acute viral respiratory tract infections (12.3% of total indications), cough (11.8%), intestinal disorders (11.3%), fever (9%), and sore throat (6.8%) . According to this study, antibiotics are widely stocked among the general population in Russia, and people use antibiotics in an uncontrolled and imprudent manner. J Clin Microbiol, 2003 Aug, 41(8), 3627 - 30 Comparison and evaluation of Osiris and Sirscan 2000 antimicrobial susceptibility systems in the clinical microbiology laboratory; Nijs A et al.; The Osiris and Sirscan 2000 systems are two semiautomated systems that can be used to read and interpret the results on disk diffusion agar plates . They are both used for determination of susceptibility to antimicrobial agents . The present study compared both systems versus the NCCLS standard method of visual reading with a ruler . Both inpatient and outpatient samples with a total of 315 nonfastidious gram-negative strains were obtained . In total, 3724 organism-antimicrobial agent combinations that fulfilled the NCCLS guidelines for disk diffusion susceptibility testing were evaluated prospectively . The results obtained with both systems in comparison with those obtained by the classical nonautomated means of interpretation were excellent, with correlation coefficients of 0.96 for both systems . The overall agreements for susceptibility interpretation were 96.56 and 96.24% with the Osiris and Sirscan systems, respectively . Very major errors were obtained for 8 (1.07%) and 10 (1.34%) organism-antimicrobial agent combinations with the Osiris and Sirscan systems, respectively . In addition, major errors were obtained for 2 (0.07%) and 6 (0.21%) combinations with the Osiris and Sirscan systems, respectively . Minor errors were obtained for 118 and 124 organism-antimicrobial agent combinations with the Osiris and Sirscan systems, respectively . Overall, both the Osiris system and the Sirscan system are comparable and reliable systems for determination of interpretative categories from the zone diameters of standard disk diffusion test plates. Expert Opin Drug Saf, 2002 Jul, 1(2), 121 - 8 Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval; Iannini PB; Macrolides, ketolides and fluoroquinolones as well as other classes of antimicrobial agents have been associated with prolongation of cardiac repolarisation . This effect is most notable with erythromycin, clarithromycin, gatifloxacin, moxifloxacin, levofloxacin and telithromycin . All of these agents produce a blockage of the HERG channel dependent potassium current in myocyte membranes resulting in a prolonged QTc interval which may give rise to polymorphic ventricular tachycardia, Torsades de Pointes or ventricular fibrillation . The risk of malignant arrhythmias is increased by concomitant usage with Type Ia or III anti-arrhythmic agents or with other drugs that prolong the QTc interval or have competitive metabolic routes . Electrolyte disturbances or underlying cardiac disease also increase the risk of ventricular arrhythmias . The best clinical outcome indicator is the incidence of the associated arrhythmias . The rough rank order of risk with these agents, albeit with limited and incomplete data, is in decreasing order; erythromycin, clarithromycin, gatifloxacin, levofloxacin and moxifloxacin . Telithromycin outcomes for associated arrhythmia are yet to be determined . The essential point is that the overall risk of ventricular arrhythmias is very small with these agents but can be reduced further by avoiding their usage for patients with other multiple risk factors for Torsades de Pointes. Expert Opin Drug Saf, 2003 May, 2(3), 287 - 304 Drug-induced cholestasis; Velayudham LS et al.; Drugs may cause several overlapping syndromes of cholestasis, the pathophysiological syndrome resulting from impaired bile flow . These reactions comprise approximately 17% of all hepatic adverse drug reactions (ADRs) and they may be severe . Causes of 'pure' (bland) cholestasis include oestrogens and anabolic steroids; rarer associations are with antimicrobials and NSAIDs . 'Cholestatic hepatitis' is a common drug reaction in which liver injury and inflammation cause significant elevation of serum alanine aminotransferase (ALT) as well as cholestasis . Chlorpromazine and ketoconazole are classic examples, but it is now exemplified by amoxycillin-clavulanate and other oxy-penicillins . Chronic cholestasis results from small bile duct injury leading to the vanishing bile duct syndrome (VBDS), a disorder mimicking primary biliary cirrhosis, or from injury to larger bile ducts causing secondary sclerosing cholangitis . Whilst there is increasing evidence of a genetic predisposition to cholestatic drug reactions, there are currently no pretreatment tests to predict drug safety . Prevention of severe reactions therefore relies on early detection of liver injury and prompt drug withdrawal . Symptomatic management includes relief of pruritus and correction of fat-soluble vitamin deficiency . In small cohort studies, ursodeoxycholic acid (UDCA) arrested progressive cholestasis in two-thirds of cases, but evidence for use of corticosteroids is anecdotal . This review considers diagnosis, pathogenesis, prevention and management of drug-induced cholestasis, with particular reference to frequently- and newly-described causes. Inflamm Bowel Dis, 2003 Jul, 9(4), 215 - 23 Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis; Wehkamp J et al.; Antimicrobial peptides such as defensins provide nonspecific mucosal defense against a multitude of microorganisms . Recently, it has been shown that luminal bacteria may invade the mucosa in inflammatory bowel diseases, suggesting a defect in innate mucosal immunity . The aim of this study was to investigate the expression of human beta-defensins (HBD) in controls, Crohn's disease (CD), ulcerative colitis (UC), and unspecific inflammation . Up to 4 biopsies were taken from 103 patients (33 controls, 24 with Crohn's disease, 36 with ulcerative colitis, 10 with unspecific colitis) . Mucosal mRNA was measured using real-time fluorescence temperature cycler reverse-transcription polymerase chain reaction with primers for HBD-1, HBD-2, HBD-3, tumor necrosis factor alpha, and interleukin 8 . Mucosal HBD-1 expression was marginally decreased in both CD and UC . HBD-2 was increased exclusively in UC but not in CD . The expression of the novel defensin HBD-3 was strongly correlated with HBD-2 and also raised predominantly in UC . The expression of both inducible beta-defensins was enhanced in the state of inflammation . Expression of HBD-2 showed a weak correlation with interleukin 8 only in inflamed CD biopsies but not with tumor necrosis factor alpha . The missing induction of both inducible beta-defensins in CD as compared with UC may cause a defect in barrier function that predisposes to bacterial invasion. J Immunol, 2003 Aug 15, 171(4), 1994 - 8 Nramp1 functionality increases inducible nitric oxide synthase transcription via stimulation of IFN regulatory factor 1 expression; Fritsche G et al.; Natural-resistance associated macrophage protein 1 (Nramp1) encodes a transmembrane phagolysosomal protein exerting resistance toward infections with intracellular pathogens by a mechanism not fully elucidated so far . We used the murine macrophage cell line RAW264.7, stably transfected with functional (RAW-37) or nonfunctional (RAW-21) Nramp1, to study for differences in the expression of NO, a central antimicrobial effector molecule of macrophages . Following stimulation with IFN-gamma and LPS, Nramp1-expressing cells exhibit higher enzymatic activity of inducible NO synthase (iNOS) and increased cytoplasmic iNOS mRNA levels than RAW-21 cells . Time-course experiments showed that iNOS-mRNA levels remain increased in RAW-37 cells after prolonged cytokine stimulation while they decrease in RAW-21 cells . Reporter gene assays with iNOS-promoter luciferase constructs demonstrated an increased and prolonged promoter activity in Nramp1-resistant vs susceptible cells . This was paralleled by increased IFN regulatory factor 1 (IRF-1) expression and binding affinity to the iNOS promoter in RAW-37 cells, which may be related to enhanced STAT-1 binding affinity in these cells . A point mutation within the IRF-1 binding site of the iNOS promoter abolished the differences in iNOS transcription between RAW-21 and RAW-37 cells . Cells carrying functional Nramp1 express increased amounts of NO, which may be related to STAT-1-mediated stimulation of IRF-1 expression with subsequent prolonged activation of iNOS transcription . Enhanced NO expression may partly underlie the protection against infection with intracellular pathogens by Nramp1 functionality. Pharmacol Res, 2003 Oct, 48(4), 389 - 95 Influence of albendazole on the disposition kinetics and milk antimicrobial equivalent activity of enrofloxacin in lactating goats; El-Sooud KA; The pharmacokinetics of single intravenous and intramuscular administrations and milk antimicrobial equivalent activity of enrofloxacin at a dose of 5 mg per kilogram body weight were studied in clinically healthy lactating goats which were either not treated or had received 7.5 mg per kilogram body weight of albendazole orally . The concentrations of enrofloxacin in serum and milk were determined using microbiological assay . Following intravenous injection, enrofloxacin antimicrobial equivalent activity versus time data in serum was described by a two-compartmental open model . Albendazole treatment significantly decreased the elimination half-life (t(1/2beta)) (P>or=0.05) and the mean residence time (MRT) (P>or=0.05), whereas, the rate of enrofloxacin return to central compartment from peripheral tissue (K(21)) was significantly increased (P>or=0.01) . In contrast, the volumes of distribution V(d(area)) and V(d(SS)) were significantly decreased (P>or=0.01 and P>or=0.05, respectively) in albendazole-treated goats . After intramuscular injection, enrofloxacin was rapidly absorbed in control and albendazole-treated lactating goats with absorption half-lives (t(1/2ab)) 0.43 and 0.39 h, respectively . The mean peaks of serum concentration (C(max)) were 0.68 and 0.65 mcg ml(-1) attained at (t(max)) 1.08 and 1.12 h, before and after albendazole dosing, respectively . The elimination half-life (t(1/2el)) and (MRT) following intramuscular injections were also shorter in the albendazole-treated lactating goats . The systemic bioavailability of enrofloxacin was significantly decreased from 110.16 to 84.38% in albendazole-treated lactating goats . Concomitant administration of albendazole with enrofloxacin resulted in significant alterations in the disposition kinetic of enrofloxacin and significant decrease in enrofloxacin concentrations in milk . Consequently, the interaction between albendazole and enrofloxacin could be of clinical significance and may require monitoring and adjustment of enrofloxacin dosage. Trends Biotechnol, 2003 Aug, 21(8), 362 - 9 Gone gene fishing: how to catch novel marine antimicrobials; Patrzykat A et al.; Medical or health-promoting products of marine origin are often regarded with skepticism--some, such as shark fins and cod liver oil, are frequently perceived as low-tech "alternative treatments" largely because they have not been exploited to their full potential . The marine environment is an enormous source of biodiversity--80% of all life is found under the oceans' surfaces--yet very little of this rich resource has been utilized . Furthermore, most marine organisms rely heavily on antimicrobial components of their innate immune defenses to combat pathogens . The past three years has seen a revolution in the methods used to identify novel antimicrobials from marine sources; among the most promising are marine cationic antimicrobial peptides (CAPs). Nucl Med Biol, 2003 Aug, 30(6), 597 - 603 In vitro and in vivo assessment of 99mTc-UBI specificity for bacteria; Ferro-Flores G et al.; Technetium-99m labeled ubiquicidin peptide 29-41 ((99m)Tc-UBI) is a cationic human antimicrobial peptide fragment that has been shown to bind bacteria in vitro and accumulates at sites of infection in experimental animals . To help determine if (99m)Tc-UBI is bound to the bacterial cell envelope by a simple nonspecific electrostatic interaction, a comparative study of the in vitro binding of (99m)Tc-UBI and two different (99m)Tc labeled cationic peptides ((99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr) to bacteria and to two tumor cell line (LS174T and ACHN) was performed . The in vivo specificity of (99m)Tc-UBI for infection in mice was also evaluated using dual labels in the same animal and comparing the target/non-target ratio for (67)Ga-citrate and (99m)Tc-UBI at sites of induced infection and sterile inflammation.Under conditions of this study, the in vitro binding of (99m)Tc-UBI, (99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr to S . aureus was 35, 78 and 87% respectively . While the binding of (99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr was 37 and 33% to colon tumor cells (LS174T) and 39 and 41% to renal tumor cells (ACHN) respectively, the binding of (99m)Tc-UBI to both cell types was much lower at less than 4% . In vivo studies revealed that there is a significant difference (p < 0.05) in the radioactive accumulation of (99m)Tc-UBI between the sites of infection and inflammation compared to (67)Ga-citrate . Thus, (99m)Tc-UBI showed an average infection/inflammation ratio of 2.08 +/- 0.49 compared to 1.14 +/- 0.45 for (67)Ga-citrate . In conclusion, the in vitro and in vivo results provide evidence that a specific mechanism is responsible of the (99m)Tc-UBI bacterial intracellular accumulation. Curr Opin Immunol, 2003 Aug, 15(4), 450 - 5 Immune evasion by Mycobacterium tuberculosis: living with the enemy; Flynn JL et al.; Mycobacterium tuberculosis is successful as a pathogen because of its ability to persist in an immunocompetent host . This bacterium lives within the macrophage, a cell whose function is the elimination of microbes . Recent advances have improved our understanding of how M . tuberculosis evades two major antimicrobial mechanisms of macrophages: phagolysosome fusion and the production of toxic reactive nitrogen intermediates . M . tuberculosis also modulates antigen presentation to prevent the detection of infected macrophages by CD4(+) T cells. FEMS Immunol Med Microbiol, 2003 Aug 18, 38(1), 59 - 64 Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells; Duits LA et al.; Human beta-defensins (hBDs) are antimicrobial peptides that play important roles in host defense against infection, inflammation and immunity . Previous studies showed that micro-organisms and proinflammatory mediators regulate the expression of these peptides in airway epithelial cells . The aim of the present study was to investigate the modulation of expression of hBDs in cultured primary bronchial epithelial cells (PBEC) by rhinovirus-16 (RV16), a respiratory virus responsible for the common cold and associated with asthma exacerbations . RV16 was found to induce expression of hBD-2 and -3 mRNA in PBEC, but did not affect hBD-1 mRNA . Viral replication appeared essential for rhinovirus-induced beta-defensin mRNA expression, since UV-inactivated rhinovirus did not increase expression of hBD-2 and hBD-3 mRNA . Exposure to synthetic double-stranded RNA (dsRNA) molecule polyinosinic:polycytidylic acid had a similar effect as RV16 on mRNA expression of these peptides in PBEC . In line with this, PBEC were found to express TLR3, a Toll-like receptor involved in recognition of dsRNA . This study shows that rhinovirus infection of PBEC leads to increased hBD-2 and hBD-3 mRNA expression, which may play a role in both the uncomplicated common cold and in virus-associated exacerbations of asthma. Biochemistry, 2003 Aug 12, 42(31), 9395 - 405 Influence of tryptophan on lipid binding of linear amphipathic cationic antimicrobial peptides; Jin Y et al.; We recently demonstrated that a linear 18-residue peptide, (KIGAKI)(3)-NH(2), designed to form amphipathic beta-sheet structure when bound to lipid bilayers, possessed potent antimicrobial activity and low hemolytic activity . The ability of (KIGAKI)(3)-NH(2) to induce leakage from lipid vesicles was compared to that of the amphipathic alpha-helical peptide, (KIAGKIA)(3)-NH(2), which had equivalent antimicrobial activity . Significantly, the lytic properties of (KIGAKI)(3)-NH(2) were enhanced for mixed acidic-neutral lipid vesicles containing phosphatidylethanolamine instead of phosphatidylcholine as the neutral component, while the potency of (KIAGKIA)(3)-NH(2) was significantly reduced {Blazyk, J., et al . (2001) J . Biol . Chem . 276, 27899-27906} . In this paper, we measured the lytic properties of these peptides, as well as several fluorescent analogues containing a single tryptophan residue, by monitoring permeability changes in large unilamellar vesicles with varying lipid compositions and in Escherichia coli cells . The binding of these peptides to lipid bilayers with defined compositions was compared using surface plasmon resonance, circular dichroism, and fluorescence spectroscopy . Surprisingly large differences were observed in membrane binding properties, particularly in the case of KIGAKIKWGAKIKIGAKI-NH(2) . Since all of these peptides possess the same charge and very similar mean hydrophobicities, the binding data cannot be explained merely in terms of electrostatic and/or hydrophobic interactions . In light of their equivalent antimicrobial and hemolytic potencies, some of these peptides may employ mechanisms beyond simply increasing plasma membrane permeability to exert their lethal effects. Biochemistry, 2003 Aug 12, 42(31), 9346 - 54 New lytic peptides based on the D,L-amphipathic helix motif preferentially kill tumor cells compared to normal cells; Papo N et al.; Despite significant advances in cancer therapy, there is an urgent need for drugs with a new mode of action that will preferentially kill cancer cells . Several cationic antimicrobial peptides, which bind strongly to negatively charged membranes, were shown to kill cancer cells slightly better than normal cells . This was explained by a slight increase (3-9%) in the level of the negatively charged membrane phosphatidylserine (PS) in many cancer cells compared to their normal counterparts . Unfortunately, however, these peptides are inactivated by serum components . Here we synthesized and investigated the anticancer activity and the role of peptide charge, peptide structure, and phospholipid headgroup charge on the activity of a new group of diastereomeric lytic peptides (containing D- and L-forms of leucine and lysine; 15-17 amino acids long) . The peptides are highly toxic to cancer cells, to a degree similar to or larger than that of mitomycin C . However, compared with mitomycin C and many native antimicrobial peptides, they are more selective for cancer cells . The peptides were investigated for (i) their binding to mono- and bilayer membranes by using the surface plasmon resonance (SPR) technique, (ii) their ability to permeate membranes by using fluorescence spectroscopy, (iii) their structure and their effect on the lipid order by using ATR-FTIR spectroscopy, and (iv) their ability to bind to cancer versus normal cells by using confocal microscopy . The data suggest that the peptides disintegrate the cell membrane in a detergent-like manner . However, in contrast to native antimicrobial peptides, the diastereomers bind and permeate similarly zwitterionic and PS-containing model membranes . Therefore, cell selectivity is probably determined mainly by improved electrostatic attraction of the peptides to acidic components on the surface of cancer cells (e.g., O-glycosylation of mucines) . The simple composition of the diastereomeric peptides and their stability regarding enzymatic degradation by serum components make them excellent candidates for new chemotherapeutic drugs. Cell Mol Biol (Noisy-le-grand), 2003 Jun, 49(4), 501 - 7 Assessment of the effect of Punica granatum (pomegranata) on the bioavailability of the radiopharmaceutical sodium pertechnetate (99mTc) in Wistar rats; Amorim LF et al.; The many desirable characteristics of technetium-99m (99mTc) have stimulated the development of labeling techniques for different molecular and cellular structures . It is generally accepted that a variety of factors other than disease can alter the bioavailability of radiopharmaceuticals and one such factor is the drug therapy . The use of medicinal plants has increased in the last decades all over the world . Punica granatum (pomegranata) is used as food or as medication in folk medicine for antiviral, anthelmintic, antifungal, antibacterial and antimicrobial activity . We have studied in rats, the effect of the medicinal plant Punica granatum on the bioavailability of the radiopharmaceutical 99mTc-sodium pertechnetate (Na(99m)TcO4) . The infusion of pomegranata was administered by intragastric via into Wistar rats during seven days . After that, the animals received by ocular plexus via, 0.1 ml of the Na(99m)TcO4 (3.7MBq) and the animals were rapidly sacrificed after 5, 20 and 40 min . The organs were isolated (brain, heart, thyroid, liver, lungs, kidneys, stomach, testis, intestines, pancreas, spleen, bladder, muscle and bone), the radioactivity determined in a well counter, the percentages of radioactivity (%ATI) in the organs were calculated and statistical analyses were performed by Wilcoxon test (p < 0.05) . The results have shown a significant (p < 0.05) increase of the activity of the Na(99m)TcO4 in spleen, heart, stomach, liver, stout bowel, pancreas, lungs and testis at 5 min . Twenty minutes after the administration of the radiopharmaceutical, the analysis of the results reveals a significant (p < 0.05) increase of the %ATI in heart, stomach, femur, pancreas, lungs and kidneys . Forty minutes after the administration of the Na(99m)TcO4, the results show a significant (p < 0.05) increase in spleen, brain, heart, stomach, liver, stout bowel, muscle, femur, lungs, pancreas, kidneys and testis . These results can be justified by therapeutic effect of this extract and/or by generation of active metabolites capable to interfere with the biodistribution of the studied radiopharmaceutical. Int Urol Nephrol, 2002, 34(3), 299 - 301 Acute pyelonephritis causing acute renal allograft dysfunction; Oguz Y et al.; In renal transplant recipients, acute pyelonephritis may cause acute deterioration of renal function . We report a case with acute allograft failure due to acute pyelonephritis, which was confirmed by graft biopsy . After appropriate antimicrobial therapy, allograft function recovered. Ann Univ Mariae Curie Sklodowska {Med}, 2002, 57(2), 119 - 26 Antimicrobial therapy of upper respiratory tract infections in children; Tokarz A et al.; Respiratory tract infections still represent a serious medical problem, mainly in people with different dysfunctions of the immune system . That kind of infections frequently occurs in the children and in the elderly . The aim of the present work was to estimate paediatrician's preferences in antibiotics prescription and therapy effectiveness in cases of ambulatory bacterial upper respiratory tract infections in children . Paediatricians working in the Lublin area were asked to fill in an inquiry that estimated their preferences to the prescription of antibiotics in children . Additionally, the microbiological examinations were performed determining the treatment effectivity . The inquiry was filled by 47 persons . The most frequently prescribed antibiotic was cefuroxime (93.6%), and the macrolids were prescribed rarely . During infection state, the predominant strain isolated was S . aureus (70.5%) and S . pyogenes (14.7%) . After treatment, there was a significant increase in C . albicans isolation (44.1%) and H . influenzae (20.5%) . There was a significant fall in isolation of S . pyogenes and S . aureus . Antibiotic prescription without earlier determination of susceptibility to antimicrobial agents had an influence on the appearance of postantimicrobial candidiosis, establishment of carrier state and increasing resistance among bacteria. J Bacteriol, 2003 Aug, 185(16), 5003 - 6 Mutational analysis of cell wall biosynthesis in Mycobacterium avium; Laurent JP et al.; The cell wall of the environmental pathogen Mycobacterium avium is important to its virulence and intrinsic antimicrobial resistance . To identify genes involved in cell wall biosynthesis, "transposome" insertion libraries were screened for mutants with altered colony morphology on medium containing the lipoprotein stain Congo red . Nineteen such mutants were isolated and mapped, including 10 with insertions in a functional island of cell wall biosynthetic genes that spans approximately 40 kb of the M . avium genome. J Bacteriol, 2003 Aug, 185(16), 4938 - 47 Conformation of a bactericidal domain of puroindoline a: structure and mechanism of action of a 13-residue antimicrobial peptide; Jing W et al.; Puroindoline a, a wheat endosperm-specific protein containing a tryptophan-rich domain, was reported to have antimicrobial activities . We found that a 13-residue fragment of puroindoline a (FPVTWRWWKWWKG-NH(2)) (puroA) exhibits activity against both gram-positive and gram-negative bacteria . This suggests that puroA may be a bactericidal domain of puroindoline a . PuroA interacted strongly with negatively charged phospholipid vesicles and induced efficient dye release from these vesicles, suggesting that the microbicidal effect of puroA may be due to interactions with bacterial membranes . A variety of biophysical and biochemical methods, including fluorescence spectroscopy and microcalorimetry, were used to examine the mode of action of puroA . These studies showed that puroA is located at the membrane interface, probably due to its high content of Trp residues that have a high propensity to partition into the membrane interface . The penetration of these Trp residues in negatively charged phospholipid vesicles resembling bacterial membranes was more extensive than the penetration in neutral vesicles mimicking eukaryotic membranes . Peptide binding had a significant influence on the phase behavior of the former vesicles . The three-dimensional structure of micelle-bound puroA determined by two-dimensional nuclear magnetic resonance spectroscopy indicated that all the positively charged residues are oriented close to the face of Trp indole rings, forming energetically favorable cation-pi interactions . This characteristic, along with its well-defined amphipathic structure upon binding to membrane mimetic systems, allows puroA to insert more deeply into bacterial membranes and disrupt the regular membrane bilayer structure. Aliment Pharmacol Ther, 2003 Aug 1, 18(3), 347 - 53 Quadruple therapy containing amoxicillin and tetracycline is an effective regimen to rescue failed triple therapy by overcoming the antimicrobial resistance of Helicobacter pylori; Chi CH et al.; AIM: To identify optimal antibiotics for second-line quadruple therapy of Helicobacter pylori after failed 1-week triple therapy . METHODS: One hundred patients were enrolled in this study after the failure of 1-week triple therapy . They were randomized to receive 1-week quadruple therapy consisting of amoxicillin, omeprazole and bismuth salts, plus either metronidazole or tetracycline . Before quadruple therapy, the H . pylori culture of each patient was tested for metronidazole resistance or clarithromycin resistance by E-test . Six weeks later, an endoscopy or 13C-urea breath test was used to define the success of H . pylori eradication . RESULTS: The H . pylori eradication rates by intention-to-treat and per protocol analysis were higher in the tetracycline group than in the metronidazole group (intention-to-treat: 78% vs . 58%, P < 0.05; per protocol: 89% vs . 67%, P < 0.05) . In the metronidazole group, but not in the tetracycline group, the per protocol eradication rate of quadruple therapy was lower for the infected isolates with metronidazole resistance than for those without metronidazole resistance (77% vs . 33%, P < 0.05) . CONCLUSION: Quadruple therapy, including tetracycline and amoxicillin, improves the H . pylori eradication rate after failed triple therapy. Rev Belge Med Dent, 2003, 58(1), 49 - 63 {Accidental extrusion of calcium hydroxide-based pastes into periapical lesions}; De Witte A et al.; Calcium hydroxide is a widely used material in endodontic treatment due to its high alkalinity and antimicrobial properties . It is thought to create a favourable environment for periradicular repair and healing, and to stimulate hard tissue formation . The aim of the present retrospective study was to evaluate the effect of accidental and voluminous overextensions of calcium hydroxide pastes into periapical lesions and tissues on the prognosis of periapical healing . It was seen that calcium hydroxide overextensions did not disfavour healing, none of the endodontic treatments failed but healing was delayed in the majority of cases and in a number of cases extrusion induced immediate flare-ups . Therefore the deliberate extrusion of calcium hydroxide into periapical tissues is not advocated. Mymensingh Med J, 2003 Jul, 12(2), 104 - 7 Pattern of bacteria and their antimicrobial susceptibility isolated from inanimate objects and hospital personnel; Rahman M et al.; Different inanimate samples collected from surgery wards and general operation theatre (GOT) as well as animate samples from surgery personnel were subjected to aerobic culture with the aim of identifying source of infections in surgical cases . The pattern of aerobic bacteria with antibiotic susceptibility isolated from those samples were reported in the present study . Out of 91 such samples, 53 and 26 were from different locations in general wards and OT respectively and 12 were comprising of hand swabs, throat swabs and nasal swabs from surgery personnel . Pathogenic bacteria were isolated from 34 samples having Pseudomonas spp . (18/34) in the top of the list followed by Esch . coli (14) . Among the Esch.coli isolates resistance to cotrimoxazole, amoxicillin and doxycycline were 78.7%, 71.4% and 57.1% respectively, whereas sensitivity to aztreonam, ceftazidime, gentamicin and ciprofloxacin were 100%, 85.8%, 78.7% and 71.4% respectively . Ceftriaxone yielded intermediate sensitive results in 21.4% strains . Isolates of Pseudomonas spp . also showed very high sensitive results to aztreonam, ceftazidime and ceftriaxone (94.7%, 94.7% and 84.2% respectively) . Ciprofloxacin and gentamicin were sensitive in 68.4% and 57.9% respectively . Susceptibility pattern showed well correlation with clinical response in infected cases. Arch Biochem Biophys, 2003 Aug 15, 416(2), 188 - 95 A 2S albumin-homologous protein from passion fruit seeds inhibits the fungal growth and acidification of the medium by Fusarium oxysporum; Agizzio AP et al.; Antimicrobial proteins have been isolated from a wide range of plant species . More recently, it has become increasingly clear that these types of proteins play an important role in the protection of plants . In this study, we investigate the presence of defense-related proteins from passion fruit (Passiflora edulis f . flavicarpa) seeds . Initially, seed flour was extracted for 2h (at 4 degrees C) with phosphate buffer, pH 5.5 . The precipitate obtained between 0 and 70% relative ammonium sulfate saturation was re-dissolved in distilled water and heated at 80 degrees C for 15 min . The resulting suspension was clarified by centrifugation and the supernatant (F/0-70) was extensively dialyzed . A Sephadex G-50 size exclusion column was employed for further separation of proteins . The fraction with antifungal activity was pooled and submitted to CM-Sepharose cation exchange . Two proteins, named Pf1 and Pf2, were eluted in 0.1 and 0.2M of salt, respectively, and submitted to reverse-phase chromatography in HPLC . This fraction inhibited the growth, in an in vitro assay, of the phytopathogenic fungi Fusarium oxysporum and colletotrichum lindemuthianum and the yeast Saccharomyces cerevisiae and strongly inhibited glucose-stimulated acidification of the medium by F . oxysporum in a dose-dependent manner . The molecular masses of these proteins, referred to now as Pf1-RP and Pf2-RP, were obtained by MALDI-TOF spectrometry and corresponded to 12,088 Da for Pf1-RP and 11,930 Da for Pf2-RP . These proteins were also subjected to automated N-terminal amino acid sequencing . Sequence comparisons for the heavy subunit of Pf2-RP showed the presence of a protein with a high degree of homology to storage 2S albumins. J Reprod Immunol, 2003 Jun, 59(1), 1 - 16 Differential expression of the natural antimicrobials, beta-defensins 3 and 4, in human endometrium; King AE et al.; beta-Defensins are small cationic molecules that have antimicrobial actions against bacteria, fungi and viruses and contribute to mucosal immune responses at epithelial sites . The female reproductive tract is an important site of defensin production and innate defences are crucial to the preservation of fertility and successful pregnancy . This study details the expression of the recently characterized defensins, HBD3 and 4, in human endometrium . Using real-time quantitative RT-PCR, we have shown that HBD3 mRNA expression is highest during the secretory phase of the menstrual cycle while HBD4 mRNA levels peak in the proliferative phase . Both antimicrobials are expressed by endometrial epithelium . Exogenous steroid hormones in the form of the combined oral contraceptive pill (COCP) alter expression of both defensins in vivo, while treatment of endometrial explants with progesterone in vitro does not alter expression of HBD3 or HBD4 . In in vitro cultures of primary endometrial epithelial cells, HBD3 mRNA expression is upregulated by treatment with inflammatory molecules including IL-1 beta+TNF alpha, IFN gamma and phorbol ester . HBD4 mRNA was not expressed in these primary cell cultures . These results show that the human endometrium expresses both HBD3 and HBD4 in a cycle-dependent manner . These natural antimicrobials will contribute to innate defences present in human endometrium protecting against uterine infection . Expression is altered as a result of hormonal contraceptive use and this may contribute to differential infection rates in COCP users relative to non-users . In addition, expression of HBD3 will be upregulated during infection allowing an increased innate immune response at this time. Fish Shellfish Immunol, 2003 Sep, 15(3), 183 - 94 A thraustochytrid protist isolated from Mercenaria mercenaria: molecular characterization and host defense responses; Anderson RS et al.; A previously undescribed thraustochytrid protist, designated C9G, was isolated from the gills of a clam, Mercenaria mercenaria, collected from the Bay of Fundy, Canada . Sequence data analysis showed C9G to be related to the clam pathogen QPX, quahog parasite unknown; however, it is not enveloped by secreted mucoid material as is the case for QPX . Clam hemocytes recognized and phagocytized C9G in vitro in the absence of plasma recognition factors . Hemocytes were also capable of killing ingested C9G, as shown by the use of a tetrazolium reduction viability assay . The mechanisms underlying intracellular antimicrobial activity are not yet established, but no detectable cytotoxic reactive oxygen species were generated during phagocytosis of C9G . Clam plasma proteins were shown to inhibit C9G growth at concentrations similar to those in unfractionated hemolymph. Am Fam Physician, 2003 Jul 15, 68(2), 323 - 8 Necrotizing soft tissue infections: a primary care review; Headley AJ; Patients with necrotizing soft tissue infections often present initially to family physicians . These infections must be detected and treated rapidly to prevent loss of limb or a fatal outcome . Unfortunately, necrotizing soft tissue infections have no pathognomonic signs . Patients may present with some evidence of cellulitis, vesicles, bullae, edema, crepitus, erythema, and fever . They also may complain of pain that seems out of proportion to the physical findings; as the infection progresses, their pain may decrease . Magnetic resonance imaging and laboratory findings such as acidosis, anemia, electrolyte abnormalities, coagulopathy, and an elevated white blood cell count may provide clues to the diagnosis . No single organism or combination of organisms is consistently responsible for necrotizing soft tissue infections . Most infections are polymicrobial, with both anaerobic and aerobic bacteria frequently present . Fungal infections also have been reported . Generally, bacterial and toxin-related effects converge to cause skin necrosis, shock, and multisystem organ failure . Aggressive debridement of infected tissues is critical to management . Antimicrobial therapy is important but remains secondary to the removal of diseased and necrotic tissues. Nippon Yakurigaku Zasshi, 2003 Aug, 122(2), 161 - 78 {Pharmacological properties and expected clinical role of an injectable new quinolone antibiotic, pazufloxacin mesilate}; Minami S et al.; Pazufloxacin mesilate (PZFX: Pasil INJECTION, Pazucross INJECTION) is a novel injectable quinolone antibiotic that was discovered by Toyama Chemical Co., Ltd . and codeveloped by Toyama Chemical Co . Ltd . and Mitsubishi Pharma Corporation . Laboratory studies indicated that PZFX reached high plasma levels quickly after intravenous administration, and it exhibited weak convulsion inducing activity, low local irritant effect, and less hypotensive activity, all of which are generally recognized as side effects associated with other injectable quinolones . PZFX has potent antibacterial and bactericidal activities against cephalosporin-, carbapenem-, and aminoglycoside-resistant strains . These favorable antibacterial and bactericidal activities gave PZFX superior therapeutic effects, compared to injectable cephalosporin antibiotics, on experimental animal infection models caused by those resistant strains . Clinical studies also revealed PZFX was as safe and effective as the injectable cephalosporin, ceftazidime, against various moderate to severe infections . Furthermore, PZFX showed good clinical effects on the infections resistant to chemotherapy by the other antimicrobial agents . These results indicate that PZFX is a viable choice for various bacterial infections . In this review, results of laboratory and clinical studies are summarized and the clinical role of PZFX among the injectable antimicrobials is discussed. Biol Reprod, 2003 Dec, 69(6), 1831 - 42 Epub 2003 Jul 30. Secreted epididymal glycoprotein 2D6 that binds to the sperm's plasma membrane is a member of the beta-defensin superfamily of pore-forming glycopeptides; Zanich A et al.; The plasma membrane of spermatozoa undergoes substantial remodeling during passage through the epididymal duct, principally because of changes in phospholipid composition, exchange of glycoproteins with epididymal fluid, and processing of existing membrane proteins . Here, we describe the interaction of an epididymal glycoprotein recognized by monoclonal antibody 2D6 with the plasma membrane of rat spermatozoa . Our goals have been to understand more about the mechanism of secretion of epididymal glycoproteins, how they interact with the sperm's plasma membrane, and their disposition within it . Reactivity to 2D6 monoclonal antibody was first detectable in principal cells in the distal caput epididymidis and as a soluble high-molecular-weight complex in the secreted fluid . It was not associated with membranous vesicles in the duct lumen . On cauda spermatozoa 2D6 monoclonal antibody recognized a 24-kDa glycoprotein (the subunit of a disulfide cross-linked homodimer of 48 kDa) that was present on the plasma membrane overlying the sperm tail . Binding of 2D6 to immature spermatozoa in vitro was cell-type specific but not species specific, and the antigen could only be extracted from cauda spermatozoa with detergents . Sequencing studies revealed that the 24-kDa glycoprotein was a member of the beta-defensin superfamily of small pore-forming glycopeptides of which several others (ESP13.2, Bin1b, E-2, EP2, HE2) are found in the epididymis . This evidence suggests that some epididymal glycoproteins are secreted into the luminal fluid in a soluble form and bind to specific regions of the sperm's surface via hydrophobic interactions . Given the antimicrobial function of beta-defensins, they have a putative role in protecting spermatozoa and the epididymis from bacterial infections. Emerg Infect Dis, 2003 Jul, 9(7), 822 - 6 Antimicrobial resistance markers of class 1 and class 2 integron-bearing Escherichia coli from irrigation water and sediments; Roe MT et al.; Municipal and agricultural pollution affects the Rio Grande, a river that separates the United States from Mexico . Three hundred and twenty-two Escherichia coli isolates were examined for multiple antibiotic resistance phenotypes and the prevalence of class 1 and class 2 integron sequences . Thirty-two (10%) of the isolates were resistant to multiple antibiotics . Four (13%) of these isolates contained class 1-specific integron sequences; one isolate contained class 2 integron-specific sequences . Sequencing showed that the class 1 integron-bearing strain contained two distinct gene cassettes, sat-1 and aadA . Although three of the four class 1 integron-bearing strains harbored the aadA sequence, none of the strains was phenotypically resistant to streptomycin . These results suggest that integron-bearing E . coli strains can be present in contaminated irrigation canals and that these isolates may not express these resistance markers. Nurs Stand, 2003 Jul 16-22, 17(44), 53 - 6, 58, 60 Post-operative wound infections; Michalopoulos A et al.; AIMS: To examine the factors influencing post-operative wound infections, such as the patient's age, sex, type and duration of surgical procedure, length of hospital stay, and the type of antibiotic prophylaxis used . In addition, to examine the level of nurses' and physicians' knowledge and application of aseptic technique procedures pre-operatively, peri-operatively and post-operatively . METHOD: The study was conducted between 1997 and 1999 at two major hospitals in Greece . One hundred and twenty six (n = 126) patients and 90 (n = 90) healthcare professionals (74 nurses and 16 physicians) were included in the study . Healthcare participants were interviewed and completed questionnaires that were designed to measure demographics, experience, infection control training and education, staffing levels, perceived deficits, and managerial support . RESULTS: The study showed that there was a high rate of infection (17.5 per cent) in both hospitals with more predominance in the male population (p < 0.05) . The length of hospital stay and type of surgical procedure were found to be significant factors in infection . In addition, the lack of awareness of aseptic techniques among nurses and physicians in several practice areas, despite the availability of a large number of relevant and well-established research findings and guidance, was also found to be significant . The duration of the operation was found to be correlated with infection (R = 0.208, p < 0.01) . Emergency surgical procedures were more susceptible to infection (p = 0.08) than scheduled procedures . The results will provide hospital administrators with strategic goals and actions that might have a significant impact on reducing infection outbreaks following surgery . CONCLUSION: Continuous education of all healthcare professionals in basic infection control procedures, policies and new information on antimicrobial resistance is recommended to increase detection and identification of surgical wound infections . A follow-up study should be conducted to measure the improvement in the use of aseptic techniques by both nurses and physicians. J Antimicrob Chemother, 2003 Sep, 52(3), 489 - 92 Epub 2003 Jul 29. Phenotypic and genotypic characterization of antimicrobial resistance in German Escherichia coli isolates from cattle, swine and poultry; Guerra B et al.; OBJECTIVE: Phenotypic and genotypic characterization of the antimicrobial resistance of German Escherichia coli strains isolated during 1999-2001 from cattle, swine and poultry . MATERIALS AND METHODS: Three hundred and seventeen isolates were tested for their resistance to 17 antimicrobial agents by broth microdilution . Resistant strains were screened by molecular methods for resistance genes, integrons and mutations in quinolone-resistance determining regions . RESULTS: Resistance was found in 40% and multiresistance in 32% of the strains . The resistance was significantly higher in isolates from poultry (61%) and swine (60%) than from cattle (25%) (P < 0.01) . The most prevalent resistances were to sulfamethoxazole, tetracycline, streptomycin, ampicillin and spectinomycin (30-15%) . For each antibiotic, the predominant resistance genes were: ampicillin, blaTEM1-like (92%); chloramphenicol, catA (68%) and cmlA1-like (36%); gentamicin, aac(3)-IV (60%); kanamycin, aphA1 (100%); streptomycin, aadA1-like (61%) and strA/B (59%); sulfamethoxazole, sul2 (66%), sul1 (42%) and sul3 (14%); tetracycline, tet(A) (66%) and tet(B) (42%); and trimethoprim, dfrA1-like (77%), dfrA17 (13%) and dfrA12 (7%) . Class 1 integrons were found in 30% of the strains . They carried dfrA1-aadA1a (40%), aadA1a (29%), sat1-aadA1a (16%), dfrA17-aadA5 (11%), oxa1-aadA1a (5%) and dfrA12-aadA2 (3%) . Eleven percent of the strains were resistant to nalidixic acid . Of these, 61% presented a reduced susceptibility to ciprofloxacin (MIC = 0.12-2 mg/L) and single mutations in gyrA or gyrA and parC genes, and 39%, full resistance to ciprofloxacin (MIC > or = 4 mg/L) and double and single mutations in gyrA and parC, respectively . CONCLUSION: The study gives baseline information on the magnitude of the resistance problem and its genetic background in contemporary German E . coli from food-producing animals. J Inorg Biochem, 2003 Aug 1, 96(2-3), 298 - 310 Synthesis, structural characterization and antimicrobial activities of 12 zinc(II) complexes with four thiosemicarbazone and two semicarbazone ligands; Kasuga NC et al.; Twelve zinc(II) complexes with thiosemicarbazone and semicarbazone ligands were prepared and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FT-IR and 1H and 13C NMR spectroscopy . Seven three-dimensional structures of zinc(II) complexes were determined by single-crystal X-ray analysis . Their antimicrobial activities were evaluated by MIC against four bacteria (B . subtilis, S . aureus, E . coli and P . aeruginosa), two yeasts (C . albicans and S . cerevisiae) and two molds (A . niger and P . citrinum) . The 5- and 6-coordinate zinc(II) complexes with a tridentate thiosemicarbazone ligand (Hatsc), ({Zn(atsc)(OAc)}(n) 1, {Zn(Hatsc)(2)}(NO(3))(2).0.3H(2)O 2, {ZnCl(2)(Hatsc)} 3 and {Zn(SO(4))(Hatsc)(H(2)O)}.H(2)O 4 {Hatsc=2-acetylpyridine(thiosemicarbazone)}), showed antimicrobial activities against test organisms, which were different from those of free ligands or the starting zinc(II) compounds . Especially, complex 2 showed effective activities against P . aeruginosa, C . albicans and moderate activities against S . cerevisiae and two molds . These facts are in contrast to the results that the 5- or 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridine-4N-morpholinethiosemicarbazone, ({Zn(mtsc)(2)}.0.2EtOH 5, the previously reported catena-poly {Zn(mtsc)-mu-(OAc-O,O')}(n) and {Zn(NO(3))(2)(Hmtsc)} {Hmtsc=2-acetylpyridine (4N-morpholyl thiosemicarbazone)}), showed no activities against the test microorganisms . The 5- and 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridinesemicarbazone, ({Zn(OAc)(2)(Hasc)} 6 and {Zn(Hasc)(2)}(NO(3))(2) 7 {Hasc=2-acetylpyridine(semicarbazone)}), showed no antimicrobial activities against bacteria, yeasts and molds . Complex {ZnCl(2)(Hasc)} 8, which was isostructural to complex 3, showed modest activity against Gram-positive bacterium, B . subtilis . The 1:1 complexes of zinc(II) with pentadentate thiosemicarbazone ligands, ({Zn(dmtsc)}(n) 9 and {Zn(datsc)}(n) 10 {H(2)dmtsc=2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone) and H(2)datsc=2,6-diacetylpyridine bis(thiosemicarbazone)}), did not inhibit the growth of the test organisms . On the contrary, 7-coordinate zinc(II) complexes with one pentadentate semicarbazone ligand and two water molecules, ({Zn(H(2)dasc)(H(2)O)(2)}(OAc)(2).5.3H(2)O 11 and {Zn(H(2)dasc)(H(2)O)(2)}(NO(3))(2).H(2)O 12 {H(2)dasc=2,6-diacetylpyridine bis(semicarbazone)}), showed modest to moderate activities against bacteria . Based on the X-ray structures, the structure-activity correlation for the antimicrobial activities was elucidated . The zinc(II) complexes with 4N-substituted ligands showed no antimicrobial activities . In contrast to the previously reported nickel(II) complexes, properties of the ligands such as the ability to form hydrogen bonding with a counter anion or hydrated water molecules or the less bulkiness of the 4N moiety would be a more important factor for antimicrobial activities than the coordination number of the metal ion for the zinc(II) complexes. J Paediatr Child Health, 2003 Jul, 39(5), 332 - 5 Antimicrobial resistance in Helicobacter pylori isolates from children; Rerksuppaphol S et al.; OBJECTIVE: To determine the resistance rate to four antimicrobial agents commonly used in the treatment of Helicobacter pylori infection in children . METHODS: Between July 1997 and January 2000, all H . pylori isolates from children undergoing gastroscopy were prospectively collected and subcultured to yield the susceptibility to four antimicrobial agents by E-test . In all, 23 isolates were tested . Demographic data, presenting symptoms, treatment regimen and clinical improvement after treatment were collected retrospectively . RESULTS: The resistance rate of H . pylori to metronidazole and clarithromycin were 43.5% and 8.7%, respectively . No H . pylori strains were resistant to amoxycillin or tetracycline . There were no statistically significant differences in age, sex, ethnicity, presenting symptoms or clinical improvement after treatment between antimicrobial-susceptible and antimicrobial-resistant groups . CONCLUSIONS: The frequent resistance of H . pylori to metronidazole and moderate resistance to clarithromycin in children are comparable with local adult data . The incidence of resistance tended to be higher in patients of non-European ethnicity, but this was not statistically significant . Given that the primary goal of therapy is eradication, and that local resistance rates are high, recommendations for H . pylori management may need to be modified to include sensitivity testing and/or determination of eradication in all patients. Avian Dis, 2003 Apr-Jun, 47(2), 476 - 80 In vitro susceptibility of Ornithobacterium rhinotracheale to several antimicrobial drugs; Soriano VE et al.; As part of the basic characterization of Ornithobacterium rhinotracheale, the minimal inhibitory concentrations of 10 antimicrobial drugs were determined for reference strains and Mexican isolates by a broth microdilution method . For optimal growth of the organisms, a supplemented brain-heart infusion broth was used . The susceptibility of O . rhinotracheale to amoxicillin, enrofloxacin, and oxytetracycline was variable . However, consistent higher minimal inhibitory concentrations values were obtained for gentamicin, fosfomycin, trimethoprim, sulfamethazine, sulfamerazine, sulfaquinoxaline, and sulfachloropyridazine . Obtained results among Mexican isolates indicate a marked antimicrobial drug resistance trend. J Periodontol, 2003 Jun, 74(6), 916 - 32 Meta-analysis of local tetracycline in treating chronic periodontitis; Pavia M et al.; BACKGROUND: Meta-analysis was used to assess the clinical efficacy of local delivery of tetracycline alone or as an adjunct to conventional mechanical therapy in patients with chronic periodontitis . METHODS: Studies were identified in MEDLINE and others sources . Meta-analyses were performed on the basis of probing depth (PD) at baseline, type of antimicrobial used, and experimental and control regimens (i.e., tetracycline plus scaling and root planing {SRP} versus SRP, tetracycline versus SRP, and tetracycline versus placebo, or no treatment) . The effect of local tetracycline was evaluated for follow-up times of 4, 8, 12, 16, 24, and 36 weeks . Sensitivity analysis was performed according to antimicrobial delivery mode (irrigation, fibers, strips) . A random effects model was used . RESULTS: The literature search identified 29 studies that met our inclusion criteria and were entered Into the meta-analysis . A significant mean reduction in PD for the combined tetracycline and SRP was observed regardless of initial probing depth and independently to the duration of follow-up . Tetracycline alone did not perform better than SRP, whereas they performed significantly better than placebo . Differences in improvement of attachment level (AL) were substantially similar to those encountered for PD . CONCLUSIONS: Our results documented that local . delivery of tetracycline improves the clinical outcomes of traditional treatment and should be considered particularly as an adjunct to SRP . Considerations regarding the adverse effects of widespread use of tetracycline should be taken into account when choosing a therapeutic strategy of chronic periodontitis. An Sist Sanit Navar, 1999 Sep-Dec, 22(3), 317 - 25 {Antimicrobial drug use in the department of internal medicine of a general hospital: prevalence study}; Rivero M et al.; OBJECTIVE: To ascertain the general pattern of hospital antimicrobial use, costs, and adequacy of treatment in the department of internal medicine of a general hospital . MATERIAL AND METHODS: A prevalence study was carried out and all department beds were visited . Every patient who was being treated with antimicrobials during or 24 hours prior to the visit was selected for the study . Treatment was considered adequate when indication, selected drug, dosage, and treatment duration were all adequate . When considering costs, only the price of the antimicrobials was evaluated . RESULTS: We identify 173 hospitalized patients, 79 (45.6%) of them were treated with 96 antimicrobial agents . The prevalence of community-acquired and hospital-acquired infections was 39.3% and 8.1%, respectively . Empirical use amounted to 77% . Overall, b-lactams antibiotics were the most frequently used (63.5%) . In 22 (27.8%) patients treatment was judged inadequate, the most frequent error being an excessive duration (17.8%) . The daily spending on antimicrobials was 187,750 ptas., representing 1,085 ptas . per hospitalized patient and day . CONCLUSIONS: A high percentage of hospitalized patients receive treatment with antimicrobial drugs . Because of the low rate of antimicrobials with a specific indication, the long antibiotic course duration, the incorrect drug choice, and even more the antimicrobial prescription in non-infected patients, strategies to improve the quality of antimicrobial use are clearly required Biophys J, 2003 Aug, 85(2), 1196 - 206 Conformation, orientation, and adsorption kinetics of dermaseptin B2 onto synthetic supports at aqueous/solid interface; Noinville S et al.; The antimicrobial activity of cationic amphipathic peptides is due mainly to the adsorption of peptides onto target membranes, which can be modulated by such physicochemical parameters as charge and hydrophobicity . We investigated the structure of dermaseptin B2 (Drs B2) at the aqueous/synthetic solid support interface and its adsorption kinetics using attenuated total reflection Fourier transform infrared spectroscopy and surface plasmon resonance . We determined the conformation and affinity of Drs B2 adsorbed onto negatively charged (silica or dextran) and hydrophobic supports . Synthetic supports of differing hydrophobicity were obtained by modifying silica or gold with omega-functionalized alkylsilanes (bromo, vinyl, phenyl, methyl) or alkylthiols . The peptide molecules adsorbed onto negatively charged supports mostly had a beta-type conformation . In contrast, a monolayer of Drs B2, mainly in the alpha-helical conformation, was adsorbed irreversibly onto the hydrophobic synthetic supports . The conformational changes during formation of the adsorbed monolayer were monitored by two-dimensional Fourier transform infrared spectroscopy correlation; they showed the influence of peptide-peptide interactions on alpha-helix folding on the most hydrophobic support . The orientation of the alpha-helical Drs B2 with respect to the hydrophobic support was determined by polarized attenuated total reflection; it was around 15 +/- 5 degrees . This orientation was confirmed and illustrated by a molecular dynamics study . These combined data demonstrate that specific chemical environments influence the structure of Drs B2, which could explain the many functions of antimicrobial peptides. Biochemistry, 2003 Aug 5, 42(30), 8976 - 87 Molecular dynamics simulations of pentapeptides at interfaces: salt bridge and cation-pi interactions; Aliste MP et al.; Peptide-membrane interactions are important for understanding the binding, partitioning, and folding of membrane proteins; the activity of antimicrobial and fusion peptides; and a number of other processes . We describe molecular dynamics simulations (10-25 ns) of two pentapeptides Ace-WLXLL (with X = Arg or Lys side chain) (White, S . H., and Wimley, W.C . (1996) Nat . Struct . Biol . 3, 842-848) in water and three different membrane mimetic systems: (i) a water/cyclohexane interface, (ii) water-saturated octanol, and (iii) a solvated dioleoylphosphatidylcholine bilayer . A salt bridge is found between the protonated Arg or Lys side chains with the carboxyl terminus at the three interfaces . In water/cyclohexane, the salt bridge is most exposed to the water phase and least stable . In water/octanol and the lipid bilayer systems, the salt bridge once formed persists throughout the simulations . In the lipid bilayer, the salt bridge is more stable when the peptide penetrates deeper into the bilayer . In one of two peptides, a cation-pi interaction between the Arg and the Trp side chains is stable in the lipid bilayer for about 15 ns before breaking . In all cases, the conformations of the peptides are restricted by their presence at the interface and can be assigned to a few major conformational clusters . Side chains facing the water phase are most mobile . In the lipid bilayer, the peptides remain in the interface area, where they overlap with the carbonyl area of the lipid bilayer and perturb the local density profile of the bilayer . The tryptophan side chain remains in the water-lipid interface, where it interacts with the lipid choline group and forms hydrogen bonds with the ester carbonyl of the lipid and with water in the interface. Eur J Immunol, 2003 Jul, 33(7), 1925 - 33 Granulysin in human serum as a marker of cell-mediated immunity; Ogawa K et al.; Granulysin is a cytolytic granule protein of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) with a broad range of antimicrobial and tumoricidal activities . Two molecular forms of granulysin, the 15-kDa precursor and 9-kDa mature form, are produced in these cells . In this study, we developed monoclonal antibodies against granulysin and found that the 15-kDa granulysin is spontaneously secreted by peripheral blood NK and T cells via a non-granule exocytotic pathway . When NK cells killed the target cells, the released granulysin levels in culture supernatants significantly increased through the granule exocytosis . The granulysin protein was found in the sera of healthy individuals at an average concentration of 3.7 +/- 3.2 ng/ml (age 0-99 years, n=244) . The serum levels of granulysin were transiently highly elevated among patients with acute viral infections . In addition, the serum granulysin levels in patients with severe immunodeficiency treated bycell therapy fluctuated proportionately to the improvement of other immunological parameters . Our results suggest that granulysin is well associated with diverse activities of NK cells and CTL in physiological and pathological settings and could be a useful novel serum marker to evaluate the overall status of host cellular immunity. Nippon Geka Gakkai Zasshi, 2003 Jul, 104(7), 494 - 8 {Antiinfective host defense mechanism: toll-like receptors and innate immunity}; Takesue Y et al.; The innate immune system has evolved as the first line of defense against invading microorganisms . The recent discovery of the toll-like receptors(TLRs) has rapidly expanded our knowledge of molecular events that initiate host-pathogen interactions . The TLRs, which are expressed on the surface of cells, involved in innate immune recognition, including macrophages and dendritic cells, have a crucial role in the detection of microbial infection . Signals initiated by the interaction of TLRs with pathogen-associated molecular patterns (PAMPs) induce activation of the inflammatory and antimicrobial innate immune response . Ten members of the TLR family have been identified, and they appear to recognize PAMPs, including lipopolysaccharide, peptidoglycan, and bacterial DNA . There has been considerable interest in how adaptive immune responses are controlled by the innate immune system . Recent studies have suggested that TLRs may control the induction of Th1 responses and that a separate system of recognition regulates the Th2 response . Thus TLR signaling represents a key component in the innate immune response to microbial infection. Pediatr Surg Int, 2003 Aug, 19(6), 436 - 8 Epub 2003 Jul 22. Wound infections in pediatric surgery: a study of 575 patients in a university hospital; Duque-Estrada EO et al.; Surgical wound infections (WI) remain a significant source of postoperative morbidity . This epidemiologic study was undertaken to determine retrospectively the incidence of postoperative WI in children in a university hospital and include critical comparisons of pediatric surgery WI rates between different international reports . As few data exist on postoperative WIs in pediatric patients, in contrast to numerous reports in adults, all infants and children undergoing operations in the pediatric surgical service in our institution during a 7-year period were reviewed for development of a WI, a total of 537 patients who underwent 575 operations . WIs occurred in 39 cases (6.7%) . Clean wounds (56.8% of patients) had an infection rate of 2.7%, clean-contaminated (23.1%) 10.5%, contaminated (12.9%) 13.5%, and dirty/infected (7.2%) 14.6% . Increasing duration of operation ( P < 0.001), contamination at operation ( P < 0.001), and a new element in the operation - a resident or intern - ( P < 0.001) were all associated with a higher incidence of infection, despite efforts at infection-control practices including improved sterilization methods and barriers, surgical technique, and availability of antimicrobial prophylaxis . The total incidence of wound infection in this population was comparable to that in other reports . Comparing children who developed a wound infection with those who did not, there were no significant differences in age, sex, American Society of Anesthesiologists preoperative assessment score, length of preoperative hospitalization, location of operation (intensive care unit vs operating room), the presence of a coexisting disease or remote infection, or the use of perioperative antibiotics . These baseline data may aid in forming strategies to lower the risk of WI in children . Our results suggest that WIs in children are related more to factors at operation than to the patients overall physiologic status. Curr Opin Crit Care, 2003 Aug, 9(4), 286 - 91 Antimicrobial strategies in surgical critical care; Imahara SD et al.; There is clear evidence that early and appropriate empiric antimicrobial therapy for suspected nosocomial infections reduces the rate of adverse outcomes . This approach necessitates a liberal antimicrobial policy, whereas observational and experimental data also suggest that excessive antibiotic use promotes the emergence of antimicrobial resistance, creating a dilemma for the intensivists and begging the question as to whether minimization of antimicrobial resistance and maximization of individual patient outcomes are mutually exclusive . Contemporary strategies are outlined for the antimicrobial management of ventilator-associated pneumonia, the most common nosocomial infection in the intensive care unit, and the use of institution-specific guidelines, invasive diagnostic approaches, and other objective criteria to ensure adequate, yet not excessive use of antimicrobials are discussed . The focus is then on relative merits of routine antifungal prophylaxis as an example of an attempt to reduce the incidence and adverse consequences of late diagnoses of fungal sepsis . Finally, the advantages and disadvantages of antimicrobial cycling as a means of reducing antimicrobial resistance in the intensive care unit are outlined. Clin Pharmacokinet, 2003, 42(9), 793 - 817 Selecting antibacterials for outpatient parenteral antimicrobial therapy : pharmacokinetic-pharmacodynamic considerations; Slavik RS et al.; Some infectious diseases require management with parenteral therapy, although the patient may not need hospitalisation . Consequently, the administration of intravenous antimicrobials in a home or infusion clinic setting has now become commonplace . Outpatient parenteral antimicrobial therapy (OPAT) is considered safe, therapeutically effective and economical . A broad range of infections can be successfully managed with OPAT, although this form of treatment is unnecessary when oral therapy can be used . Many antimicrobials can be employed for OPAT and the choice of agent(s) and regimen should be based upon sound clinical and microbiological evidence . Assessments of cost and convenience should be made subsequent to these primary treatment outcome determinants . When designing an OPAT treatment regimen, the pharmacokinetic and pharmacodynamic characteristics of the individual agents should also be considered . Pharmacokinetics (PK) is the study of the time course of absorption, distribution, metabolism and elimination of drugs (what the body does to the drug) . Clinical pharmacokinetic monitoring has been used to overcome the pharmacokinetic variability of antimicrobials and enable individualised dosing regimens that attain desirable antimicrobial serum concentrations . Pharmacodynamics (PD) is the study of the relationship between the serum concentration of a drug and the clinical response observed in a patient (what the drug does to the body) . By combining pharmacokinetic properties (peak {C(max)} or trough {C(min)} serum concentrations, half-life, area under the curve) and pharmacodynamic properties (susceptibility results, minimum inhibitory concentrations {MIC} or minimum bactericidal concentrations {MBC}, bactericidal or bacteriostatic killing, post-antibiotic effects), unique PK/PD parameters or indices (t > MIC, C(max)/MIC, AUC(24)/MIC) can be defined . Depending on the killing characteristics of a given class of antimicrobials (concentration-dependent or time-dependent), specific PK/PD parameters may predict in vitro bacterial eradication rates and correlate with in vivo microbiologic and clinical cures . An understanding of these principles will enable the clinician to vary dosing schemes and design individualised dosing regimens to achieve optimal PK/PD parameters and potentially improve patient outcomes . This paper will review basic principles of useful PK/PD parameters for various classes of antimicrobials as they may relate to OPAT . In summary, OPAT has become an important treatment option for the management of infectious diseases in the community setting . To optimise treatment course outcomes, pharmacokinetic and pharmacodynamic properties of the individual agents should be carefully considered when designing OPAT treatment regimens. Biotechnol Lett, 2003 Feb, 25(3), 205 - 11 A recombinant human G-CSF/GM-CSF fusion protein from E . coli showing colony stimulating activity on human bone marrow cells; Lee AY et al.; Granulocyte-Macrophage colony stimulating factor (GM-CSF) and Granulocyte colony stimulating factor (G-CSF) are cytokines involved in the differentiation of bone marrow progenitor cells into myeloid cells . They also activate mature myeloid cells to mediate a variety of antimicrobial activities and inflammatory responses . Recombinant GM-CSF and G-CSF proteins have been used to treat various diseases including cancer and hematopoietic diseases and to isolate peripheral blood progenitor cells for bone marrow transplantation . A plasmid construct expressing recombinant human G-CSF/GM-CSF fusion protein has now been prepared by linking the human G-CSF and GM-CSF coding regions and the recombinant fusion protein has been successfully expressed in E . coli . The recombinant human G-CSF/GM-CSF fusion protein was extracted and purified from the cellular inclusion and refolded into the biologically active form to show colony stimulating activity . The recombinant fusion protein exhibited colony stimulating activity on human bone marrow cell cultures, indicating that the linkage of GM-CSF and G-CSF by a linker peptide may not interrupt activities of the cytokines in the fusion protein . The colony forming unit of the fusion protein was also higher than those of the cultures treated with the same molar numbers of the recombinant human GM-CSF and G-CSF separately, which suggests that the fusion protein presumably retains both G-CSF and GM-CSF activities. Curr Probl Dermatol, 2003, 31, 64 - 81 Laundering in the prevention of skin infections; Kurz J; The statistics at the Hohenstein Institutes and the detergent industry show that the number of complaints due to skin irritations or allergies of washed laundry are relatively low . A clear interdependence between the number of complaints and the season of the year is existing . An interesting fact is that work wear made of cotton shows a relatively higher number of complaints than blends of polyester with cotton . The highest number of complaints results from operating theatre textiles, which is probably due to the exceptional strain of the skin of the operating-theatre staff by surgical disinfecting measures . During washing in household washing machines and also in the industrial sector it is mainly the mechanical action of the washing machines and the chemistry of the detergents which influence the textiles . The effects of the washing process on the textiles if assessed regarding the dermatological point of view, can go in two different directions: Changes of the textile itself and the formation of residues on the washed laundry, whereby the residues can be unintended, i.e . inevitable or desired, so to speak as finishing, for example optical brighteners, softeners, etc . The changes of the textile substance itself can result in a raising . This can either mean that the textile becomes more harsh in feel or fluffier . Textiles which become harsher only have little influence on the skin . Whereas the change to a fluffier textile has positive effects on the skin as there are so-called 'distance holders' formed on the textile surface, which prevents an early sticking of the textiles to a perspirating skin . This increases the wear comfort . Inevitable residues on the washed laundry can be caused by wear (this is not important), the washing water and the detergent . Within the detergents only the surfactants and alkalines are of interest . Desired residues are for example optical brighteners to increase the degree of whiteness, softeners, finishing baths (starch), scents and water-repellent finishes . Regarding special cases like for example flame-retardant finishes, antistatic additives and antimicrobial effects, there is only little experience available so far. Semin Pediatr Infect Dis, 2003 Apr, 14(2), 108 - 14 Brain abscess in children; Saez-Llorens X; Brain abscess is a relatively uncommon but life-threatening infection in children . It can originate from contiguous site infections (eg, chronic otitis media, mastoiditis, sinusitis, meningitis), from distant pathologic states (eg, cyanotic congenital heart disease, chronic lung infections), after head trauma or neurosurgical procedures, or from cryptogenic sources . Predominant etiologic microorganisms vary depending on these predisposing factors . Computed tomography and magnetic resonance imaging are essential tools that enable the physician to make an accurate diagnosis of intracranial purulent collections . Proper selection of antimicrobial agents with good penetration of the central nervous system and with adequate coverage of both anaerobic and aerobic bacteria is critical for the medical management of brain abscess . Delay in surgical drainage can be associated with high morbidity and case-fatality rates . In the early phase of cerebritis, however, infection can respond to antibiotic therapy alone . Advances in diagnostic and therapeutic modalities during the last decade have improved the prognosis of this serious disease . Blood, 2003 Nov 15, 102(10), 3693 - 701 Epub 2003 Jul 24. Flexible migration program regulates gamma delta T-cell involvement in humoral immunity; Brandes M et al.; gamma delta T cells are inadequately defined both in terms of their migration potential and contribution to antimicrobial immunity . Here, we have examined the migration profile of human blood gamma delta T cells and related cell lines and correlated these findings with their distribution in secondary lymphoid tissues and their function in B-cell cocultures . We find that resting gamma delta T cells are characterized by an inflammatory migration program similar to cells of the innate immune system . However, T-cell receptor (TCR) triggering resulted in the rapid but transient induction of a lymph node (LN)-homing program, as evidenced by functional CCR7 expression and concomitant reduction in expression and function of CCR5 and, to a lesser degree, CCR2 . Moreover, the LN-homing program was reflected by the presence of gamma delta T cells in gastrointestinal lymphoid tissues, notably in clusters within germinal centers of B-cell follicles . In line with these findings, V gamma V delta-TCR triggering resulted in prominent expression of essential B-cell costimulatory molecules, including CD40L, OX40, CD70, and ICOS . Furthermore, gamma delta T cells were shown to provide potent B-cell help during in vitro antibody production . Collectively, our findings agree with a role for gamma delta T cells in humoral immunity during the early phase of antimicrobial responses. Burns, 2003 Aug, 29(5), 445 - 8 Assessment of a silver-coated barrier dressing for potential use with skin grafts on excised burns; Holder IA et al.; Acticoat burn dressing is a silver-coated dressing with antimicrobial activity purported to reduce infection from environmental organisms in partial and full-thickness wounds . Acticoat was tested for activity as an antimicrobial treatment and as an antimicrobial barrier dressing in three in vitro assays . It was found that a modified disc assay method gave false negative results but in an assay in which bacteria were inoculated on top of samples of Acticoat, bacterial numbers were reduced, over time, with all microorganisms tested . Acticoat served as a barrier for bacteria, inoculated onto it, from contaminating the surface of an agar plate under the Acticoat . The data show that Acticoat has: antimicrobial capabilities, but to be effective hours of contact between Acticoat and the microorganisms are required; and the capacity to serve as an antimicrobial barrier dressing . These findings support the conclusion that Acticoat has activity to reduce microbial contamination of wounds from environmental sources. J Pediatr Endocrinol Metab, 2003 Jun, 16(5), 727 - 31 Serum leptin levels in neonatal bacterial septicemia; Orbak Z et al.; The principal aim of this study was to evaluate serum leptin concentrations and to analyze the interaction between serum leptin levels and C-reactive protein (CRP) levels, hematological parameters before and after antimicrobial therapy in neonates with bacterial septicemia . We studied 16 neonates with bacterial septicemia and 15 controls . Blood samples in neonates with septicemia were collected just before antimicrobial therapy and 2 weeks after treatment . The mean concentration of serum leptin, CRP levels, and immature/total neutrophil (IT) ratio in newborns with septicemia were significantly higher than those of controls at the start . Two weeks after treatment, serum leptin levels in newborns with septicemia had decreased and were similar to those of controls . Although there were positive correlations between serum leptin levels and serum CRP levels and IT ratio in the septicemic group at the start, there were no correlations between serum leptin levels and other hematological parameters . These results suggest that leptin is not only an adipostatic hormone but also a stress-related hormone. Clin Liver Dis, 2003 May, 7(2), 381 - 99, vi-vii Hepatotoxicity of antibiotics and antifungals; Thiim M et al.; Hepatotoxicity associated with any antibiotic is rare . With the wide-spread use of antimicrobial agents, however, hepatic injury is not an infrequent occurrence . Penicillins remain a widely used class of antimicrobials with a well defined record of low hepatotoxicity . The combination of clavulanate with amoxicillin may be associated with the greatest risk for liver injury from any antimicrobial agent . Significant hepatotoxicity also may occur with sulfamethoxazole/ trimethoprim and combination regimens used to treat tuberculosis . An autoimmune-like hepatitis may result from minocycline or nitrofurantoin exposure and most often resolves with cessation of therapy . Treatment with high doses of tetracycline and oxacillin may be associated with severe hepatotoxicity . Early suspicion of hepatocellular injury in the setting of antimicrobial exposure should prompt cessation of therapy and avoidance of rechallenge. Am J Health Syst Pharm, 1995 Jan 15, 52(2), 183 - 5 Pharmacist-managed Helicobacter pylori clinic; Morreale AP; A pharmacist-managed Helicobacter pylori assessment clinic for ambulatory patients is described . The pharmacy service at a 400-bed Veterans Affairs Medical Center established a pharmacist-managed clinic to assess patients who were receiving long-term acid-suppressive medications (histamine H2-receptor antagonists, sucralfate, or omeprazole) . Patients with active ulcer disease and those receiving ulcer prophylaxis are screened for the presence of H . pylori . Those who test positive are treated with combinations of the following agents: omeprazole, clarithromycin, amoxicillin, tetracycline, and metronidazole . The pharmacist also may adjust or discontinue acid-suppressive drug regimens . The pharmacist is responsible for ordering all appropriate laboratory tests, monitoring patients for adverse effects, collecting data on patient outcomes, and providing patient education . The clinic provides opportunities for pharmacists to study the clinical effectiveness and pharmacoeconomics of various regimens for treating H . pylori-associated disease and for pharmacy students and residents to interact with patients . As of fall 1994, 20 patients had been evaluated at the clinic: 12 tested positive for H . pylori and were treated with antimicrobials and all were pain-free without medication at the end of treatment . An H . pylori assessment clinic enabled pharmacists to assume a primary care role, document improvement in patient outcomes, and study the effectiveness of various antimicrobial regimens. Proc Natl Acad Sci U S A, 2003 Aug 5, 100(16), 9173 - 8 Epub 2003 Jul 23. Biosynthesis of isoprenoids: crystal structure of 4-diphosphocytidyl-2C-methyl-D-erythritol kinase; Miallau L et al.; 4-Diphosphocytidyl-2C-methyl-d-erythritol kinase, an essential enzyme in the nonmevalonate pathway of isopentenyl diphosphate and dimethylallyl diphosphate biosynthesis, catalyzes the single ATP-dependent phosphorylation stage affording 4-diphosphocytidyl-2C-methyl-d-erythritol-2-phosphate . The 2-A resolution crystal structure of the Escherichia coli enzyme in a ternary complex with substrate and a nonhydrolyzable ATP analogue reveals the molecular determinants of specificity and catalysis . The enzyme subunit displays the alpha/beta fold characteristic of the galactose kinase/homoserine kinase/mevalonate kinase/phosphomevalonate kinase superfamily, arranged into cofactor and substrate-binding domains with the catalytic center positioned in a deep cleft between domains . Comparisons with related members of this superfamily indicate that the core regions of each domain are conserved, whereas there are significant differences in the substrate-binding pockets . The nonmevalonate pathway is essential in many microbial pathogens and distinct from the mevalonate pathway used by mammals . The high degree of sequence conservation of the enzyme across bacterial species suggests similarities in structure, specificity, and mechanism . Our model therefore provides an accurate template to facilitate the structure-based design of broad-spectrum antimicrobial agents. Antimicrob Agents Chemother, 2003 Aug, 47(8), 2688 - 91 Bovine lactoferrin inhibits adenovirus infection by interacting with viral structural polypeptides; Pietrantoni A et al.; We recently demonstrated that lactoferrin, an antimicrobial glycoprotein, can inhibit adenovirus infection by competing for common glycosaminoglycan receptors . This study further characterizes the antiadenovirus activity of the protein, thus demonstrating that lactoferrin neutralizes infection by binding to adenovirus particles and that its targets are viral III and IIIa structural polypeptides. Antimicrob Agents Chemother, 2003 Aug, 47(8), 2644 - 5 In vitro activities of tigecycline (GAR-936) and 12 other antimicrobial agents against 90 Eikenella corrodens clinical isolates; Cercenado E et al.; The activity of tigecycline was compared with those of other antimicrobials against 90 isolates of Eikenella corrodens . The MIC at which 90% of the isolates were inhibited was 2 micro g/ml for tigecycline and 1, </=0.5/0.25, 0.5, </=0.12, </=2, and 0.5 micro g/ml for ampicillin, amoxicillin-clavulanate, cefotaxime, imipenem, chloramphenicol, and ciprofloxacin, respectively. Antimicrob Agents Chemother, 2003 Aug, 47(8), 2545 - 50 Subinhibitory concentrations of the deformylase inhibitor actinonin increase bacterial release of neutrophil-activating peptides: a new approach to antimicrobial chemotherapy; Fu H et al.; Bacterial protein synthesis starts with a formylated methionine residue, and this residue is sequentially cleaved away by a unique peptide deformylase (PDF) and a methionine aminopeptidase to generate mature proteins . The formylation-deformylation of proteins is a unique hallmark of bacterial metabolism and has recently become an attractive target for the development of antimicrobial agents . The innate immune system uses the formylation of bacterial proteins as a target, and professional phagocytes, e.g., neutrophils, express specific receptors for bacterium-derived formylated peptides . Activation of formyl peptide receptors (FPR) mediates neutrophil migration and the release of oxygen radicals and other antimicrobial substances from these cells . We hypothesize that the use of a PDF inhibitor would increase the production of proinflammatory peptides from the bacteria and thus trigger a more pronounced innate immune response . We tested this hypothesis by exposing Escherichia coli to subinhibitory doses of the PDF inhibitor actinonin and show that actinonin indeed increases the production and secretion of neutrophil-activating peptides that activate human neutrophils through FPR . These findings could be potentially used as a new approach to antibacterial chemotherapy. Antimicrob Agents Chemother, 2003 Aug, 47(8), 2481 - 6 Biological activities of synthetic analogs of halocidin, an antimicrobial peptide from the tunicate Halocynthia aurantium; Jang WS et al.; Halocidin is a heterodimer antimicrobial peptide previously isolated from the tunicate Halocynthia aurantium . Based on the larger monomer (18Hc) of halocidin, nine halocidin congeners, including a series of 6 peptides truncated successively from the carboxyl-terminal end of 18Hc and 3 analogs (18HcKK, K19Hc, and K19HcKK), which have lysine residues in place of two internal histidines or have a lysine added to the amino terminus of the 18Hc molecule, were prepared . Each peptide was also converted into a homodimeric version . The antimicrobial activities of halocidin congeners truncated from the C terminus were dramatically decreased, suggesting that the full length of 18Hc is required for maintaining its maximum antimicrobial activity . Dimer forms of halocidin congeners exhibited stronger antimicrobial activities than the monomer of the corresponding peptide . Four dimer peptides (di-18Hc, di-18HcKK, di-K19Hc, and di-K19HcKK) were analyzed for antimicrobial activities against 10 clinically isolated antibiotic-resistant bacteria in elevated concentrations of NaCl or MgCl(2) . Of the peptides studied here, di-K19Hc retained invariably strong activity against all bacteria in diverse conditions and also showed much reduced hemolytic activity against human erythrocytes. Lancet Neurol, 2003 Aug, 2(8), 473 - 81 Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs; Patsalos PN et al.; Antiepileptic drugs (AEDs) are commonly prescribed for long periods, up to a lifetime, and many patients will require treatment with other agents for the management of concomitant or intercurrent conditions . When two or more drugs are prescribed together, clinically important interactions can occur . Among old-generation AEDs, carbamazepine, phenytoin, phenobarbital, and primidone are potent inducers of hepatic enzymes, and decrease the plasma concentration of many psychotropic, immunosuppressant, antineoplastic, antimicrobial, and cardiovascular drugs, as well as oral contraceptive steroids . Most new generation AEDs do not have clinically important enzyme inducing effects . Other drugs can affect the pharmacokinetics of AEDs; examples include the stimulation of lamotrigine metabolism by oral contraceptive steroids and the inhibition of carbamazepine metabolism by certain macrolide antibiotics, antifungals, verapamil, diltiazem, and isoniazid . Careful monitoring of clinical response is recommended whenever a drug is added or removed from a patient's AED regimen. Int J Food Microbiol, 2003 Aug 25, 85(3), 249 - 58 Development of a method to quantify in vitro the synergistic activity of "natural" antimicrobials; Dufour M et al.; Despite numerous papers being published on the use of hurdle technology to control food-borne pathogens or spoilage organisms, there is no commonly accepted methodology to quantify the level of synergistic activity . This paper describes a method to quantify in vitro the synergistic activity of antibacterial agents against bacteria . Initially, a microtiter plate growth assay was used to determine the inhibitory concentrations of four "natural" antimicrobials (nisin, lauricidin, totarol, and the lactoperoxidase system (LPS)) against a panel of eight bacteria . Using the same microtiter system, the impact of various combinations of antimicrobials was assessed . The degree of synergy was based on the analysis of three criteria: (1) increase in lag phase, (2) reduction in culture density after 24 h, (3) and residual viability at 24 h . Only the lactoperoxidase system was active against all the Gram-positive and Gram-negative bacteria tested . Nisin, lauricidin, and totarol were only effective against the Gram-positive bacteria . The method successfully identified three combinations (nisin-lauricidin, LPS-nisin, and LPS-lauricidin) previously reported to have synergistic activity and highlighted the synergistic activity of two novel combinations (nisin-totarol and LPS-totarol) . The development of a quick and reliable method to identify and quantify synergistic activity is a useful screening tool to establish preservative techniques that could have potential antimicrobial synergy in food-based systems. Phytochemistry, 2003 Aug, 63(7), 789 - 93 Flavanoids from Caesalpinia pulcherrima; Srinivas KV et al.; Two new flavanoids, 5,7-dimethoxy-3',4'-methylenedioxyflavanone and isobonducellin along with 2'-hydroxy-2,3,4',6'-tetramethoxychalcone, 5,7-dimethoxyflavone and bonducellin were isolated from the aerial parts of Caesalpinia pulcherrima . The structures of the compounds were settled mainly by interpretation of their 1D and 2D NMR spectra . Isobonducellin was found to be a homoisoflavanoid containing a cis (Z)-double bond . Antimicrobial activity of the new compounds was evaluated. Scand J Prim Health Care, 2003 Jun, 21(2), 121 - 6 Treatment of acute rhinosinusitis diagnosed by clinical criteria or ultrasound in primary care . A placebo-controlled randomised trial; Varonen H et al.; OBJECTIVES: To compare antibiotics and placebo in patients with clinically diagnosed acute maxillary sinusitis (AMS) . To study whether sinus ultrasound examination would help to detect those patients who benefit from antibiotic therapy . DESIGN: A double-blind, randomised, placebo-controlled multicentre trial . SETTING: Nine primary care sites in Finland . SUBJECTS: 150 adult patients (mean age 39.7 years) with a clinical diagnosis of sinusitis . INTERVENTION: Antibiotics (amoxicillin 750 mg x 2, doxycycline 100 mg x 2 or penicillin V 1500 mg x 2) or placebo twice daily for 7 days; all patients were examined with sinus ultrasound after randomisation . MAIN OUTCOME MEASURE: Clinical success (patients' report of recovery) in telephone interview at 2 weeks . RESULTS: A total of 146 patients completed the 2-week follow-up . Patients receiving antibiotics achieved a slightly higher rate of clinical success than patients receiving placebo (80% vs 66%; p = 0.068) . CONCLUSIONS: Antibiotics hasten symptom relief in AMS . Yet many patients recover in 2 weeks without antimicrobial treatment . Only half of patients with a clinical diagnosis of AMS have sinusitis in ultrasound examination. J Endod, 2003 Jul, 29(7), 450 - 2 In vitro antimicrobial efficacy of MTAD and sodium hypochlorite; Shabahang S et al.; The purpose of this study was to compare the ability of a mixture of a tetracycline isomer, an acid, and a detergent (MTAD) with that of sodium hypochlorite (NaOCI) to disinfect human root canals that had been contaminated with whole saliva . One hundred and thirty-two root canals of extracted human teeth were cleaned and shaped using the passive step-back technique and rotary NiTi files . The smear layer was removed, and the teeth were autoclaved . Six autoclaved samples were transferred to sterile broth without contamination with saliva to serve as negative controls . Whole saliva was used to contaminate the root canals of the rest of the samples for 48 h . Six of these contaminated samples were irrigated with Brain Heart Infusion (BHI) broth and served as positive controls . The rest of the contaminated specimens were then divided into two experimental groups of 60 teeth each . In one group, the canals were irrigated with 1 ml MTAD, and the samples were immersed in 2 ml of the same solution for 5 min . In the second group, the specimens were similarly treated with 5.25% NaOCl . All samples were washed in BHI broth and then placed in another tube containing BHI broth and incubated for 96 h . Disinfection of the samples was determined based on presence or absence of turbidity in the broth 96 h later . Twenty-three of 60 teeth treated with NaOCl remained infected . Only one of 60 teeth treated with MTAD remained infected . Statistical analysis of the data using the Chi-square test showed a significant difference between the two groups (p < 0.0001). Scand J Infect Dis, 2003, 35(5), 337 - 8 Biotypes and antimicrobial susceptibilities of Brucella isolates; Bodur H et al.; 41 Brucella strains isolated from blood and cerebrospinal fluid cultures were identified to species level and biotypes detected . All of the isolates were Brucella melitensis: 2 strains of B . melitensis biotype-1 and 39 strains of B . melitensis biotype-3 . In vitro activities of these strains were detected by the E test method . According to the 90% minimal inhibitory concentration (MIC90) values, the most active agent was doxycycline (MIC90 0.064 microg/ml), followed by ciprofloxacin (MIC90 0.25 microg/ml), trimethoprim-sulfamethoxazole and ceftriaxone (MIC90 0.38 microg/ml) . Rifampin exhibited the highest MIC90 value (0.75 microg/ml). J Am Vet Med Assoc, 2003 Jul 15, 223(2), 206 - 9, 196 Ultrasonographic detection of ingested and perforating wooden foreign bodies in four dogs; Penninck D et al.; Four dogs that had ingested wooden foreign bodies were examined . All 4 dogs were young and were examined because of lethargy and a mass involving the left flank that was partially responsive to antimicrobial treatment . Ultrasonography of the flank mass revealed inhomogeneous subcutaneous tissues representing seroma, edema, or reactive tissue . Long, linear, bright interfaces representing the wooden foreign bodies were identified in the stomach of 3 dogs and in the abdominal cavity of 1 dog . The interfaces were associated with uniform shadowing in 3 dogs . Local omental and mesenteric changes suggestive of focal peritonitis were evident in 1 dog . In all 4 dogs, the foreign bodies were removed through an exploratory celiotomy . All dogs recovered without complications. Int J Clin Pharmacol Ther, 2003 Jul, 41(7), 287 - 93 Factors influencing antimicrobial utilization at a university hospital during a period of 11 years; Vlahovic-Palcevski V et al.; OBJECTIVE: A number of factors may influence antibiotic prescribing . The objective of this study was to identify trends in antimicrobial prescribing during a period of 1 years at the University Hospital Center Rijeka (UHC), Croatia, and to identify possible factors that might have influenced changes in prescribing patterns . This may help in establishing criteria for future intervention . METHODS: Antimicrobial utilization was evaluated retrospectively for the 11-year period from 1990-2000 . It was measured in defined daily doses (DDDs) per 100 bed days using the ATC Index with DDDs 2000 . RESULTS: During the investigation period, marked differences were noted in total and individual antimicrobial consumption . In the first 4 years of this study, the utilization of all groups of antimicrobials decreased, while in its second part (i.e . from 1995-1997) an increase in utilization of all antimicrobial groups occurred . Changes in utilization of groups of antimicrobials did not coincide completely with the changes in total antimicrobial utilization . The most prominent changes were a decrease in penicillin and cephalosporin utilization, and an increase of macrolides and aminoglycosides utilization from 1997-2000 . Ampicillin and cefalexin were mostly prescribed as single antibiotics during a 5-year period (1990-1995) with the exception of 1 year (1994) when a marked decline in antimicrobial utilization was noted . In the following years, amoxicillin and amoxicillin with enzyme inhibitor became the most-used antimicrobials . CONCLUSION: Various factors influenced antimicrobial utilization during the investigation period . There were factors that directly influenced prescribing, e.g . the physicians' prescribing habit, guidelines, policy and formulary . Other factors directly influenced utilization, e.g . availability of a drug through purchasing, dispensing, procurement, pricing etc. Trop Doct, 2003 Jul, 33(3), 151 - 3 Brucellosis: a retrospective evaluation; Tasbakan MI et al.; One hundred and sixty-six presumed brucellosis patients were included in the study . These patients were classified as primary (91), relapse (18) and suspected (57) cases according to their clinical presentations, and serologic and microbiologic test results . Primary and relapse cases were evaluated retrospectively according to age, sex, residence, routes of transmission, clinical and laboratory findings, treatment regimens, duration of treatment, and relapse rates . Of the 109 primary and relapse patients, 57 were male and 52 female . The ages of the patients ranged between 16-75 (mean age 40.2) . The percentages of the urban and rural residence of the patients were 41.3% and 58.7%, respectively . The most common mode of transmission was consumption of unpasteurized milk and milk products (67.9%) . Malaise, fever and sweating were the most frequently observed symptoms (96.3%, 95.4%, 91.7%, respectively) . The most common signs were fever (97.2%), splenomegaly (59.6%), and hepatomegaly (37.6%) . The liver was the most frequently involved organ (21.1%) . Almost all (99.1%) patients were serologically positive . However, the positivity rate of culture was low (15.6%) . The most frequently preferred antimicrobial regimen was rifampin and doxycycline combination . The relapse rate was 8.3% . Brucellosis is still prevalent in Turkey as in many other countries in the Mediterranean basin . The clinical presentation of the disease may show regional variations . Patients with a history of occupational or nutritional contact with the bacterium and with a compatible clinical picture should be examined using appropriate diagnostic techniques before any attempt to prescribe an antimicrobial. Curr Opin Oncol, 2003 Jul, 15(4), 283 - 8 New antifungal drugs and new clinical trials: interpreting results may be difficult; Girmenia C et al.; PURPOSE OF REVIEW: In recent years, considerable progress in the management of invasive mycoses in immunocompromised patients has been achieved . However, the prognosis of these infections, in particular those caused by filamentous fungi, continues to be dramatically poor, with mortality rates reaching more than 80% in selected categories of patients . New antifungal drugs in the classes of triazoles and echinocandins, with interesting antimicrobial and pharmacokinetic characteristics, are under investigation, and important trials have been reported in the last 2 years . These studies seem to suggest the relevant role of these new drugs in the antifungal armamentarium . RECENT FINDINGS: The triazole voriconazole and the echinocandin caspofungin demonstrated significant advantages in term of toxicity and response rate, when compared with conventional amphotericin B in the treatment of aspergillosis and candidiasis, respectively . However, because of the peculiar characteristics of the design of both studies, the interpretation of the results may be difficult, and further confirmatory experiences are needed . Other noncontrolled studies showed a promising role of caspofungin in the treatment of Aspergillus infections and of voriconazole in the treatment of other rare mycoses . SUMMARY: The increasing incidence and severity of invasive mycoses have led to the development of new strategies with new antifungal agents, and amphotericin B no longer is the gold standard for a variety of fungal infections . However, these results should be considered with caution . The latest generation drugs need to be investigated further in proper trials, and old drugs, especially conventional amphotericin B, continue to have a central role in the antifungal armamentarium. Infect Immun, 2003 Aug, 71(8), 4711 - 6 Calprotectin, an abundant cytosolic protein from human polymorphonuclear leukocytes, inhibits the growth of Borrelia burgdorferi; Lusitani D et al.; We previously showed that numerous polymorphonuclear leukocyte (PMN) granule components efficiently kill Borrelia burgdorferi, the agent of Lyme disease . In addition, motile, granule-poor cytoplasts (U-Cyt) from human blood PMN can exert anti-Borrelia activity against opsonized B . burgdorferi independently of oxidative mechanisms . Here we show that lysates of U-Cyt also possess anti-Borrelia activity, a portion of which comes from the abundant cytosolic protein calprotectin . The anti-Borrelia activity of U-Cyt lysates and recombinant calprotectin was partially or completely reversed by specific antibody to calprotectin and by Zn(2+), a cation essential for the growth of B . burgdorferi and known to inhibit the antimicrobial activity of calprotectin . Quantitative microscopic and regrowth assays revealed that calprotectin acted in a bacteriostatic fashion against B . burgdorferi . We conclude that calprotectin, a potent bacteriostatic agent from a cell primarily recognized for its oxidative and granular antibacterial mechanisms, may play a modulatory role in infection by the Lyme spirochete, particularly at sites of acute inflammation. Bioorg Med Chem Lett, 2003 Aug 18, 13(16), 2699 - 702 Search compounds with antimicrobial activity by applying molecular topology to selected quinolones; Mut-Ronda S et al.; Molecular topology was used to obtain substances with antimicrobial activity . Selected quinolones were employed to develop the corresponding connectivity functions and discriminant equation . Limiting functions were selected that allowed the discriminant function to more efficiently distinguish substances with and without antibacterial activity . Antibacterial tests were run to confirm the theoretically established activity. Int Surg, 2003 Apr-Jun, 88(2), 105 - 8 Major reasons to prescribe antimicrobial prophylaxis in surgery; Azzam RA et al.; Based on the Belgian recommendation for antimicrobial prophylaxis (AMP) in surgery in 1996, a prospective survey of 3 months was carried out in 10 acute care hospitals in Lebanon to describe the major reasons to prescribe AMP in surgery . Of 961 surgical procedures, 767 (80%) received one or several antibiotics; the surgical site infection rate was 4% . Results indicate that duration of procedures over 1 hour and patient older than 60 years represent the main reasons for prescribing AMP in Lebanese hospitals. Int J Hyg Environ Health, 2003 Jun, 206(3), 217 - 21 Bactericidal activity of herbal extracts; Thuille N et al.; The antimicrobial activity of total herbal extracts has been investigated . The MIC of extracts of Evodia rutaecarpa and grape kernel ranged between 0.25 and 1 mg/ml against gram-positive cocci and P . aeruginosa . Cocci were killed after 30-90 min of incubation in grape kernel extract (0.5-1.5 mg/ml), and after 8 h in evodia extract (0.5-1 mg/ml), respectively . C . albicans was only susceptible to evodia (MIC 0.5 mg/ml) . The organic solvents of the preparations contributed to the antibacterial effect of herbal extracts with MICs of ethanol between 4 and 10 vol% and those of methanol between 6 and 10 vol% . Taking this into consideration, mastic and thyme extracts exerted hardly any microbicidal activity, while grape kernel extract and evodia were still effective at 2- to 6-fold dilutions below the MIC of the solvent . Because of the weak antimicrobial activity of total herbal extracts we recommend to give preference to preparations of single or more purified compounds. Gac Med Mex, 2003 May-Jun, 139(3), 199 - 204 {Descending Necrotizing Mediastinitis . Results of Medical-Surgical Treatment in 17 Cases }; Perez A et al.; Descending necrotizing mediastinitis (DNM) is a serious disease of the mediastinum; early diagnosis and treatment may lower the high mortality rate of this disease . OBJECTIVE: To know the frequency of DNM in an intensive respiratory care unit . MATERIAL AND METHODS: This is a retrospective, transversal, and observational trial of a series of consecutive cases . In a period from January 1, 1990 to December 31, 2000, among 1,560 patients, we found 17 patients with DNM according with selection criteria . RESULTS: Fifteen males and two females, mean age 38.9 years SD +/- 14.5 years, were studied . In 10, tracheostomy was practiced previously . Seventeen cases had different kinds of previous abscesses, seven periodontal (47%), six retropharyngeal (35.5%), and four (23.5%) submaxillary . All cases were subject to thoracotomy . The most frequent postoperative complications were septic shock in 10 cases (58.8%), eight acute pulmonary damage (47%), six gastrointestinal bleeding (35.6%) and three acute respiratory insufficiency syndrome (11.6%) . Seven deaths were registered and 10 patient survived . CONCLUSIONS: Statistical significance found between survival patients vs those who died was 31.9 +/- 8.6 vs 48.1 +/- 14.1 (p < 0.05) and in those with early tracheostomy 8.0 vs 28.6 (p = 0.68) . Death occurred most frequently due to septic shock, specific mortality in this group of patients was 29% . Although DNM is a rare entity, 1.08% of all reviewed cases, must be treated immediately due to high mortality . The importance of early antimicrobial and surgical treatments is stressed. Muscle Nerve, 2003 Aug, 28(2), 133 - 43 Lyme disease and the peripheral nervous system; Halperin JJ; Lyme disease, the multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi, causes a broad variety of peripheral nerve disorders, including single or multiple cranial neuropathies, painful radiculopathies, and diffuse polyneuropathies . Virtually all appear to be varying manifestations of a mononeuropathy multiplex . Diagnosis requires that the patient should have had possible exposure to the only known vectors, Ixodes ticks, and also have either other pathognomonic clinical manifestations or laboratory evidence of exposure . Treatment with antimicrobial regimens is highly effective . The mechanism underlying these neuropathies remains unclear, although interactions between anti-Borrelia antibodies and several peripheral nerve constituent molecules raise intriguing possibilities. Protein Pept Lett, 2003 Jun, 10(3), 227 - 38 Antimicrobial peptides from anurans skin secretions; Nascimento AC et al.; This article is an overview of antimicrobial peptides found in anurans skin secretions . These molecules constitute an initial barrier against microbial infections because of their activity against a large array of microorganisms . These peptides hold remarkable pharmaceutical and technological interest since they selectively kill microorganisms and are unlikely to induce resistance in pathogens . Also, outstanding synergism occurs when these peptides are combined with classic antibiotics and other antimicrobial peptides. Curr Med Chem, 2003 Sep, 10(17), 1689 - 95 Towards the design and development of agents with broad spectrum chemotherapeutic properties for the effective treatment of HIV / AIDS; Sriram D et al.; HIV is the most significant risk factor for many opportunistic infections like fungal, tuberculosis, etc . The intense media coverage of AIDS puts the public on an emotional roller caster, and inflated promises are engendered by each success . For the moment drugs acting as both HIV-reverse transcriptase inhibitors along with antimicrobial properties are one of the brightest hope . The Non-nucleoside reverse transcriptase inhibitors (NNRTIs) appear ideally suited for further development in the chemoprophylaxis and therapy of HIV infections . In recent years, isatinimino compounds have been reported to exhibit broad-spectrum chemotherapeutic properties that include anti-HIV, antituberculous, antifungal and antibacterial activities . Hence these leads should be regarded as structural hits in the search for more potent antimicrobial compounds with broad-spectrum chemotherapeutic properties for the effective treatment of HIV / AIDS . This review focuses on the design of isatinimino compounds, which resemble the NNRTIs for the development of an ideal anti-HIV drug. Curr Drug Targets Immune Endocr Metabol Disord, 2003 Sep, 3(3), 210 - 21 Evidences for iNOS expression and nitric oxide production in the human macrophages; Panaro MA et al.; Nitric oxide (NO) is a pleiotropic mediator of numerous biological processes, including smooth muscle relaxation, neurotransmission and defence against pathogens . In addition, NO is involved in the pathogenesis and control of inflammation, tumors, autoimmunity, and infectious and chronic degenerative diseases . NO, a highly reactive radical, is produced from L-arginine and oxygen by the enzyme NO synthase (NOS) . Three NOS isoforms have been identified: two distinct NOS isoforms are constitutively expressed in cells, whereas a third isoform, inducible NOS (iNOS), is transcribed in response to specific stimuli . In particular, iNOS is responsible for the discontinuous synthesis of high amounts of NO and was originally characterized in murine macrophages after exposure to cytokines and/or microbial products . A wide range of microorganisms is sensibly inhibited in its development by NO, like fungi, bacteria, protozoa and viruses . Although NO production and its antimicrobial effect appear well established in rodent macrophages, the existence of L-arginine pathway in human mononuclear phagocytes has long been disputed . Recently, evidences showing the iNOS activity and NO production in other animal models, including humans, are now emerging, even if the NO induction has been more difficult to demonstrate . The present observations provide evidence for the occurrence of iNOS protein expression and NO production in human macrophages cultured in vitro. J Food Prot, 2003 Jul, 66(7), 1288 - 91 Composition and antimicrobial properties of Sardinian Juniperus essential oils against foodborne pathogens and spoilage microorganisms; Cosentino S et al.; In this work, the chemical compositions and antimicrobial properties of Juniperus essential oils and of their main components were determined . Five berry essential oils obtained from different species of Juniperus growing wild in Sardinia were analyzed . The components of the essential oils were identified by gas chromatography-mass spectrometry (GC-MS) analysis . The antimicrobial activities of the oils and their components against food spoilage and pathogenic microorganisms were determined by a broth microdilution method . The GC-MS analysis showed a certain variability in the concentrations of the main constituents of the oils . Alpha-pinene was largely predominant in the oils of the species J . phoenicea subsp . turbinata and J . oxycedrus . Alpha-pinene and myrcene constituted the bulk (67.56%) of the essential oil of J . communis . Significant quantitative differences were observed for myrcene, delta-3-carene, and D-germacrene . The results of the antimicrobial assay show that the oils of J . communis and J . oxycedrus failed to inhibit any of the microorganisms at the highest concentrations tested (MLC > or = 900 microg/ml), while the oils extracted from J . turbinata specimens were active against fungi, particularly against a strain of Aspergillus flavus (an aflatoxin B1 producer) . Of the single compounds tested, delta-3-carene was found to possess the broadest spectrum of activity and appeared to contribute significantly to the antifungal activity observed for J . turbinata oils . This activity may be helpful in the prevention of aflatoxin contamination for many foods. Mol Cell Biochem, 2003 Jun, 248(1-2), 35 - 40 Evaluation of the effect of lipoic acid administered along with gentamicin in rats rendered bacteremic; Varalakshmi P et al.; Gentamicin is an aminoglycosidic antibiotic widely used in the treatment of many gram-negative bacterial infections . The present study was designed to investigate the extent of nephrotoxicity and the degree of protection afforded by lipoic acid under E . coli infected conditions and to note its effect on the antimicrobial activity of gentamicin . The study was carried out with adult male albino rats of Wistar strain . Group I animals served as controls . Group II animals were injected intraperitoneally for 2 successive days with 0.2 ml inoculum containing 10(10)) colony forming units of E . coli . Group III animals were injected E . coli as those in group II, in addition gentamicin 100 mg kg(-1) was administered intraperitoneally for 10 successive days . Group IV animals received intraperitoneal injections of E . coli as above plus gentamicin and also received lipoic acid (25 mg kg(-1)) for 10 days by oral gavage . Rats subjected to E . coli administration showed a decline in the thiol content of the cell accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase and glutathione peroxidase with an added effect observed when gentamicin was administered along with it . The extent of nephrotoxicity induced by gentamicin was clearly evident with the decline in the activities of lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-D-glucosaminidase in the rat renal tissues . A significant decrease was also observed in the activities of the transmembrane enzymes upon gentamicin administration . Treatment with lipoic acid decreased lipid peroxidation thereby maintaining the antioxidant status of the cell . The activities of the renal and transmembrane enzymes were also restored on lipoic acid treatment . The study has highlighted the beneficial effects of lipoic acid against experimental aminoglycoside toxicity in rats rendered bacteremic. Int J Health Care Qual Assur Inc Leadersh Health Serv, 2003, 16(2-3), 128 - 35 Compliance with instructions for writing structured care management tools; Labarere J et al.; The aim of this study was to assess whether clinical guidelines complied with the instructions for writing structured care management tools in a French university hospital . A cross-sectional study of guidelines for appropriate antimicrobial agent use in the authors' institution was carried out . A total of 221 guidelines were retrieved in 62 hospital units . The number of guidelines by unit ranged from one to 22 and 198 guidelines (90 per cent) had been developed at the local level . None of the guidelines fully complied with the ten criteria of the instructions . Each guideline met, on average, 4.2 criteria (3.9-4.5) . The partial compliance rate was 75 per cent (68-80) . In two-level multivariate analysis, factors associated with partial compliance were: dissemination of guidelines after implementation of the instructions (odds ratio = 6.25 (2.41-16.21)), existence of more than one storage site for guidelines in each unit (OR = 3.26 (1.03-10.32)), and hospital unit (variance of the intercept = 1.54). Blood, 2003 Aug 1, 102(3), 1100 - 7 Transforming growth factor-beta1 in supernatants from stored red blood cells inhibits neutrophil locomotion; Ghio M et al.; Studies comparing transfusion and nontransfusion patients suggest an increased risk of postoperative infections in transfusion groups . Supernatants of blood components have been shown to affect the function of T lymphocytes and natural killer cells . Here, we found that supernatants from stored red blood cells (RBCs) inhibit human neutrophil migration in response to formyl peptides and stimulate neutrophil locomotion . These effects can be observed with high dilutions of RBC supernatants, such as 1:5 x 106 (vol/vol), able to trigger locomotion as well as desensitization of the cells to alternative chemoattractants . The phenomenon might be mediated by chemoattractants present in the supernatants . As RBC supernatants failed to mobilize intracellular free calcium, the chemoattractants should belong to the group of pure chemoattractants, that is, soluble Fas ligand (sFasL) and transforming growth factor-beta1 (TGF-beta1), known to act without increasing calcium levels . Recombinant TGF-beta1, but not sFasL, was found to reproduce the ability of RBC supernatants to both inhibit neutrophil response to formyl peptides and stimulate neutrophil locomotion . Moreover, TGF-beta1-immunodepleted supernatants did not display neutrophil-directed activities . Finally, RBC supernatants from RBCs stored after depletion of leukocytes were incapable of affecting neutrophil function . With neutrophils acting as a first-line antimicrobial defense, the ability, shown here, of high dilutions of RBC supernatants to inhibit neutrophil chemotaxis through TGF-beta1 may be a relevant determinant of infections in the postoperative period for transfusion patients . Consistently, the neutrophil chemotactic response to formyl peptide was inhibited by the plasma obtained from 5 transfusion patients. Clin Exp Immunol, 2003 Aug, 133(2), 252 - 9 BPI-ANCA in transporter associated with antigen presentation (TAP) deficiency: possible role in susceptibility to Gram-negative bacterial infections; Schultz H et al.; Although HLA class I expression is diminished in patients with defects in the transporter associated with antigen presentation (TAP), recurrent Gram-negative bacterial lung infections are found from childhood onwards . As MHC class II-mediated responses are normal, other mechanisms that contribute to susceptibility to infections are presumed . The bactericidal/permeability-increasing protein (BPI) is a potent neutrophil antibiotic that neutralizes endotoxin efficiently . As antineutrophil cytoplasmic autoantibodies (ANCA) against BPI were found in the majority of cystic fibrosis patients and correlate with disease severity we examined the prevalence of BPI-ANCA and their contribution to susceptibility to bacterial infections in six TAP-deficient patients . Although only two patients showed ANCA in indirect immunofluorescence, BPI-ANCA occurred in five of six patients in ELISA . Purified IgG from BPI-ANCA-positive sera (five of six) inhibited the antimicrobial function of BPI in vitro . Epitope mapping revealed binding sites not only on the C-terminal but also on the antibiotic N-terminal portion of BPI, indicating that short linear BPI peptide fragments may be long-lived enough to become immunogens . In conclusion, BPI-ANCA are associated strongly with TAP deficiency . Inhibition of the antimicrobial BPI function by BPI-ANCA demonstrates a possible mechanism of how autoantibodies may contribute to increased susceptibility for pulmonary Gram-negative bacterial infections by diminished bacterial clearance. Contact Dermatitis, 2003 May, 48(5), 261 - 5 Allergic contact dermatitis in venous leg ulcer patients; Tavadia S et al.; Our aim was to determine the frequency and nature of contact sensitivity in venous leg ulcer patients in Lanarkshire . We performed patch testing with the European standard series, antimicrobials and medicaments on 200 patients referred to our leg ulcer clinics . Positive patch tests were found in 136 (68%) patients . Multiple allergies occurred in 102 (51%) . The most frequent allergen groups were fragrances (30.5%), antimicrobials (19.5%), topical excipients (19.5%), rubber accelerators (13.5%) and topical corticosteroids (8%) . We also found a high prevalence of positive patch tests to Intrasite gel (9.5%) and Hioxyl cream (8.5%), medicaments which are commonly used to treat leg ulcers in our area . Contact sensitivity is common in venous leg ulcer patients and has important implications for patient management . The allergens involved vary depending on local nursing practice . We suggest that all venous leg ulcer patients be patch tested with a locally relevant patch test series. J Postgrad Med, 2003 Apr-Jun, 49(2), 118 - 22 Antimicrobial-induced endotoxaemia in patients with sepsis in the field of acute pyelonephritis; Giamarellos-Bourboulis EJ et al.; BACKGROUND: In vitro results have shown that antimicrobial agents may induce the Gram-negative bacteria to release endotoxins (LPS), which in turn, could trigger the secretion of cytokines from monocytes . AIMS: To compare the effect of cefuroxime, netilmicin or ciprofloxacin on serum levels of LPS and tumour necrosis factor-alpha (TNFalpha) . METHODS: Seventy-four patients with acute pyelonephritis caused by Gram-negative bacteria and signs of sepsis were randomly assigned to receive one of three intravenous regimens of cefuroxime, netilmicin or ciprofloxacin . Blood samples were collected before therapy and at specified time intervals for 96 hours after the initiation of treatment for the determination of serum levels of LPS and of TNFalpha . RESULTS: Patients treated with cefuroxime presented an early peak of LPS and of TNFalpha in serum two hours after the initiation of treatment compared to the other study groups . After that time interval, concentrations of LPS and TNFalpha were similar in all the study groups . Fever accompanied by endotoxaemia was still detected for 48 hours after the start of therapy in 36, 37.5 and 36% of patients treated with cefuroxime, netilmicin and ciprofloxacin respectively . The corresponding figures for these agents at 72 hours were 28, 12.5 and 24%, respective and 12, 4.2 and 4% at 96 hours (P value not significant) . CONCLUSIONS: With the exception of an early peak in the serum levels of LPS and TNFalpha in patients treated with cefuroxime, no significant difference could be detected amongst the study groups as far as their effect on serum levels of LPS and TNFalpha were concerned . This suggests that these three antimicrobial agents may be administered safely at the early stages of sepsis. J Med Microbiol, 2003 Aug, 52(Pt 8), 643 - 51 Reassessment of the microbicidal activity of reactive oxygen species and hypochlorous acid with reference to the phagocytic vacuole of the neutrophil granulocyte; Reeves EP et al.; During phagocytosis, neutrophils undergo a burst of respiration in which oxygen is reduced to superoxide (O(-)(2)), which dismutates to form H(2)O(2) . Myeloperoxidase (MPO) is discharged from the cytoplasmic granules into the phagosome following particle ingestion . It is thought to utilize H(2)O(2) to oxidize halides, which then react with and kill ingested microbes . Recent studies have provided new information as to the concentration of O(-)(2) and proteins, and the pH, within the vacuole . This study was conducted to examine the antimicrobial effect of O(-)(2), H(2)O(2) and hypochlorous acid under these conditions and it was found that the previously described bactericidal effect of these agents was reversed in the presence of granule proteins or MPO . To establish which cellular proteins were iodinated by MPO, cellular proteins and bacterial proteins, iodinated in neutrophils phagocytosing bacteria in the presence of (125)I, were separated by 2D gel electrophoresis . Iodinated spots were detected by autoradiography and the oxidized proteins were identified by MS . The targets of these iodination reactions were largely those of the host cell rather than those of the engulfed microbe. Clin Ther, 2003 May, 25(5), 1321 - 81 Voriconazole; Jeu L et al.; BACKGROUND: Reports of resistance and intolerance to currently available antifungal agents are increasing . Voriconazole is a broad-spectrum azole antifungal agent structurally derived from fluconazole . It is indicated for the treatment of invasive aspergillosis and serious fungal infections caused by Scedosporium apiospermum and Fusarium species in patients who are unable to tolerate or are refractory to other antifungal therapy . OBJECTIVE: This article reviews the pharmacologic and pharmacokinetic properties and clinical usefulness of voriconazole . METHODS: Relevant information was identified through a search of MEDLINE (1966-December 2002), Iowa Drug Information Service (1966-December 2002), International Pharmaceutical Abstracts (1970-December 2002), and meeting abstracts of the Infectious Diseases Society of America (1996-2002) and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1996-2002) using the terms voriconazole and UK-109,495 . RESULTS: In head-to-head comparative trials, voriconazole appeared to be as efficacious as amphotericin B for the treatment of invasive aspergillosis and the empiric treatment of fungal infections in patients with febrile neutropenia . In clinical studies, it was as efficacious as fluconazole for the treatment of oropharyngeal and esophageal candidiasis . The results of in vitro susceptibility studies and case reports suggested that voriconazole may be useful against fluconazole- and/or itraconazole-resistant strains of Candida . Although voriconazole may be associated with a lower incidence of serious systemic adverse effects compared with amphotericin B (13.4% vs 24.3% in 1 pivotal clinical study; P = NS), major adverse effects associated with voriconazole include visual abnormalities ( approximately 30%), skin reactions ( approximately 20%), and elevations in hepatic enzymes (< or =20%) . Voriconazole is available as oral and intravenous formulations . Pharmacokinetically, it has widespread distribution, including penetration into cerebral tissue . However, as 80% of voriconazole is hepatically eliminated, primarily via the cytochrome P450 (CYP) isozymes CYP2C19, CYP3A4, and CYP2C9, voriconazole has a high potential for drug interactions, and dose reduction is recommended in patients with mild to moderate hepatic dysfunction (Child-Pugh class A or B) . Oral voriconazole may be preferred in patients with a creatinine clearance <50 mL/min due to the potential accumulation of the solubilizing excipient in the parenteral formulation of voriconazole . CONCLUSIONS: Voriconazole appears to be a useful alternative to conventional antifungal agents in cases of resistance or intolerance to initial therapy . However, dose adjustment is recommended in patients with hepatic dysfunction, as well as in those receiving medications that may interact with voriconazole via hepatic metabolism. AAPS PharmSci . 2003;5(2):E8. Development of a multidose formulation for a humanized monoclonal antibody using experimental design techniques; Gupta S et al.; The purpose of this study was to identify optimal preservatives for a multidose formulation of a humanized monoclonal antibody using experimental design techniques . The effect of antimicrobial parenteral preservatives (benzyl alcohol, chlorobutanol, methylparaben, propylparaben, phenol, and m-cresol) on protein stability was assessed using size-exclusion chromatography, differential scanning calorimetry, right-angle light scattering, UV spectroscopy, and potency testing using a cell-based fluorescence-activated cell sorting method . A quick, cost-effective preservative screening test was designed . Combinations of preservatives were examined using an I-optimal experimental design . The protein was most stable in the presence of methylparaben and propylparaben, and was compatible with benzyl alcohol and chlorobutanol at low concentrations . Phenol and m-cresol were not compatible with the protein . The I-optimal experimental design indicated that as an individual preservative, benzyl alcohol was promising . The model also indicated several effective combinations of preservatives that satisfied the antimicrobial efficacy and physical stability constraints . The preservative screening test and the experimental design approach were effective in identifying optimal concentrations of antimicrobial preservatives for a multidose protein formulation; (1) benzyl alcohol, and (2) the combination of methylparaben and chlorobutanol were screened as potential candidates to satisfy the regulatory requirements of various preservative efficacy tests. Syst Appl Microbiol, 2003 Jun, 26(2), 293 - 301 Occurrence and diversity of mesophilic Shewanella strains isolated from the North-West Pacific Ocean; Ivanova EP et al.; Although bacteria of the genus Shewanella belong to one of the readily cultivable groups of "Gammaproteobacteria", little is known about the occurrence and abundance of these microorganisms in the marine ecosystem . Studies revealed that of 654 isolates obtained from marine invertebrates (ophiuroid Amphiopholis kochii, sipuncula Phascolosoma japonicum, and holothurian Apostichopus japonicus, Cucumaria japonica), seawater and sediments of the North-West Pacific Ocean (i.e . the Sea of Japan and Iturup Is, Kurile Islands), 10.7% belonged to the genus Shewanella . The proportion of viable Shewanella species varied from 4% to 20% depending on the source of isolation . From the isolation study, representative strains of different phenotypes (from seventy presumptive Shewanella strains) were selected for detailed characterization using phenotypic, chemotaxonomic, and phylogenetic testing . 16S rDNA sequence-based phylogenetic analysis confirmed the results of tentative identification and placed the majority of these strains within only a few species of the genus Shewanella with 98-99% of 16S rDNA sequences identity mainly with S . japonica and S . colwelliana, suggesting that the strains studied might belong to these species . Numerically dominant strains of S . japonica were metabolically active and produced proteinases (gelatinases, caseinases), lipases, amylases, agarases, and alginases . Shewanella strains studied demonstrated weak antimicrobial and antifungal activities that might be an indication of their passive role in the colonization on living and non-living surfaces. Postepy Hig Med Dosw, 2003, 57(2), 185 - 98 {Effect of tetracycline on metabolic processes in bones}; Folwarczna J; Tetracyclines, antibiotics widely used in medical practice, have many effects independent of their antimicrobial activity, among others they exert anti-collagenolytic activity . The paper presents a review of literature concerning the effects of tetracyclines on the skeletal system. MMW Fortschr Med, 2003 May 29, 145(22), 37 - 9 {Urogenital infections in the male and the desire to father a child}; Siebels M; Urogenital infections may often have a major effect on fertility . For the most part, however, the pathogenetic aspects of such cases have not yet been clarified . In the future, the integration of functional and molecular parameters will be decisive for defining an interaction between urogenital infection and male fertility . As a rule, infection-related alterations to the ejaculate require antimicrobial treatment, although the effect of the latter on fertility remains uncertain. Planta Med, 2003 Jun, 69(6), 579 - 82 Dissectol A, an unusual monoterpene glycoside from Incarvillea dissectifoliola; Chen W et al.; An unusual monoterpene glycoside named dissectol A ( 1) was isolated from the EtOH extract of Incarvillea dissectifoliola, and its structure was determined by 1D and 2D NMR data . The antimicrobial bioassays showed that dissectol A had modest inhibitory activity against Mycobacterium tuberculosis when compared to rifampicin in an agar diffusion assay. J Antimicrob Chemother, 2003 Aug, 52(2), 253 - 7 Epub 2003 Jul 15. Pharmacokinetic/pharmacodynamic relationship of danofloxacin against Mannheimia haemolytica in a tissue-cage model in calves; Greko C et al.; OBJECTIVE: To evaluate an experimental model of the pharmacokinetic/pharmacodynamic (PK/PD) relationship of danofloxacin against Mannheimia haemolytica infection, using subcutaneously implanted tissue cages in calves . METHODS: Tissue cages implanted subcutaneously in calves were infected with M . haemolytica and different concentration-time profiles of danofloxacin were simulated . Drug concentrations and bacterial counts were monitored over time and various PK/PD parameters calculated . RESULTS: By using different types of cage and various doses, a range of PK/PD indices were simulated . The PK/PD index that best predicted the antimicrobial effect was the AUC/MIC ratio . The magnitude of this index needed for near-maximum effect (80%), assessed using the area under the bacterial kill curve to 48 h, was 244 h . CONCLUSIONS: The model described enabled different concentration-time profiles to be simulated, and PK/PD interactions to be studied in the presence of the host's defences . The validity of this model needs to be confirmed by clinical studies, but the results suggest that it may be a useful intermediary step between in vitro and clinical studies. J Antimicrob Chemother, 2003 Aug, 52(2), 199 - 203 Epub 2003 Jul 15. Comparative antimicrobial activities of gatifloxacin, sitafloxacin and levofloxacin against Mycobacterium tuberculosis replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines; Sato K et al.; Mycobacterium tuberculosis (MTB) is capable of invading not only macrophages (Mphis) but also type II pneumocytes . In this study, we compared the antimicrobial activities of fluoroquinolones, including gatifloxacin, sitafloxacin and levofloxacin, against the MTB replication in the Mono Mac 6 human Mphi cell line (MM6-Mphis) and the A-549 human type II alveolar epithelial cell line (A-549 cells) . When test quinolones were added at the MIC (0.125, 0.06 and 0.25 mg/l for gatifloxacin, sitafloxacin and levofloxacin, respectively) to the culture media of MTB-infected cells, these drugs exerted growth-inhibitory activity against intracellular organisms in the order of sitafloxacin > gatifloxacin > levofloxacin . On the other hand, when test quinolones were added at Cmax in the blood (1.7, 1.0 and 2.0 mg/l for gatifloxacin, sitafloxacin and levofloxacin, respectively), these drugs exhibited bactericidal activity against intracellular MTB in the order of gatifloxacin > sitafloxacin > or = levofloxacin . In addition, when test drugs were added at 1/8 C(max) to 1/2 C(max), the efficacy was in the order of sitafloxacin > gatifloxacin > levofloxacin . Thus, it appears that the MIC values of fluoroquinolones are not always predictive of their antimicrobial activity against intracellular MTB . In this context, it was also found that intracellular uptake of these quinolones by MM6-Mphis and A-549 cells was in the order of sitafloxacin > gatifloxacin > levofloxacin . This implies that the cellular permeability of these quinolones is an important factor that determines their efficacy to eliminate intracellular MTB organisms. Curr Gastroenterol Rep, 2003 Aug, 5(4), 295 - 301 Current concepts in peritonitis; Malangoni MA; Peritonitis is a serious and common infection . Its pathogenesis and microbiology have been well defined . Such risk factors as age, site of infection, physiologic response of the patient, presence of organ dysfunction, and malnutrition may influence the outcome of this disease process . The presence of antibiotic-resistant organisms and delays in operative intervention are also associated with treatment failure and higher mortality . Surgeons have the greatest impact on this disease in their ability to control the source of infection and to administer proper antimicrobial therapy. Curr Gastroenterol Rep, 2003 Aug, 5(4), 287 - 94 Diagnosis and treatment of bacterial diarrhea; Lawler JV et al.; Diarrheal illness caused by bacterial pathogens is a global health problem and remains one of the most common complaints prompting patients to seek medical care . Strategies to increase the yield of stool culture and new rapid diagnostic tests can improve diagnostic ability . Emerging antimicrobial resistance among the common bacterial causes of diarrhea has made treatment more challenging . Emerging fluoroquinolone resistance is a particular concern . Recent studies of rifaximin, a nonabsorbed antibiotic for the treatment of bacterial diarrhea, have shown favorable results . Rifaximin may represent a much-needed addition to the armamentarium against bacterial agents. Curr Gastroenterol Rep, 2003 Aug, 5(4), 273 - 8 Gastrointestinal tuberculosis; Sheer TA et al.; Gastrointestinal tuberculosis is defined as infection of the peritoneum, hollow or solid abdominal organs, and abdominal lymphatics with Mycobacterium tuberculosis organisms . Gastrointestinal tuberculosis is relatively rare in the United States and is the sixth most common extrapulmonary location . Populations at risk include immigrants to the United States, the homeless, prisoners, residents of long-term care facilities, and the immunocompromised . The peritoneum and the ileocecal region are the most likely sites of infection and are involved in the majority of cases by hematogenous spread or through swallowing of infected sputum from primary pulmonary tuberculosis . Pulmonary tuberculosis is apparent in less than half of patients . Patients usually present with abdominal pain, weight loss, fever, anorexia, change in bowel habits, nausea, and vomiting . The diagnosis is often delayed and is usually made through a combination of radiologic, endoscopic, microbiologic, histologic, and molecular techniques . Antimicrobial treatment is the same as for pulmonary tuberculosis . Surgery is occasionally required. Drug Saf, 2003, 26(10), 691 - 706 Drug-induced myelosuppression : diagnosis and management; Carey PJ; Myelosuppression is a common and anticipated adverse effect of cytotoxic chemotherapy . It is a potential but rare idiosyncratic effect with any other drug, but there is a recognised association with a number of higher-risk agents which justify additional vigilance . Genetic risk factors are being identified which may predispose individuals to this reaction with particular drugs . As marker tests become available, dose adjustment or alternative treatment choices may help to avoid more severe reactions . Myelosuppression is potentially life threatening because of the infection and bleeding complications of neutropenia and thrombocytopenia . Strategies for monitoring, early detection, diagnostic confirmation and appropriate supportive care are well developed for cytotoxic therapy . Developments in antimicrobial chemotherapy, blood product transfusion support and growth factor therapy have improved outcomes . These advances are largely applicable to idiosyncratic drug-induced myelosuppression, reinforcing the importance of early recognition and referral to appropriate expertise . Many reactions will resolve on drug withdrawal with appropriate supportive care during the period of cytopenia . Prolonged marrow failure may require more specific treatment with intensive immunosuppression or consideration of bone marrow transplantation. Am J Rhinol, 2003 May-Jun, 17(3), 149 - 52 In vitro study on the influence of N-chlorotaurine on the ciliary beat frequency of nasal mucosa; Hofer E et al.; BACKGROUND: The aim of this study was to investigate the in vitro effects of N-chlorotaurine (NCT), a new endogenous antimicrobial agent, on the nasal ciliary beat frequency (CBF) in nasal mucosa samples of 10 adult patients who underwent conchotomy . METHODS: CBF was measured by a photometric technique, combining a light microscope, a photometer, a photograph multiplier, and a computed analyzing unit . RESULTS: CBF decreased approximately 10% after 20 minutes of incubation in aqueous 1% NCT solution compared with 3% in 0.9% saline, and 0.1 and 0.01% NCT had no effect . However, a solution of 7% cocaine, which is used routinely for shrinking the nasal mucosa before rhinoscopy lowered the CBF to 50% after the same incubation time . CONCLUSION: These results confirm the very low toxic potential of NCT, and they are fundamental for clinical investigations regarding its topical application in the nasal and paranasal sinuses. Vestn Ross Akad Med Nauk, 2003, (6), 3 - 9 {Current understanding of the pathogenesis of infectious diseases}; Pimenov EV et al.; New experimental data in such research fields as molecular biology, biochemistry, genomics and others as well as the changes occurring in the medical-and-epidemiological situation in respect to a number of infectious diseases dictate the necessity to systemize and to revise the appropriate knowledge for the purpose of ensuring a more profound understanding of the processes providing a foundation for the relations within the system of "host--parasite" . The article deals with modern aspects of investigating the pathogenesis of infectious diseases, i.e . issues of the genetic and of structural-and-functional organization as well as of regulation of the pathogenetic potential of microorganisms; and mechanism of antimicrobial protection of microorganisms including from the standpoint of evolutionary biology. J Biomed Mater Res B Appl Biomater, 2003 Aug 15, 66(2), 502 - 13 Biocompatibility and other properties of acrylic bone cements prepared with antiseptic activators; de la Torre B et al.; Acrylic bone cements prepared with activators of reduced toxicity have been formulated with the aim of improving the biocompatibility of the final material . The activators used were N,N-dimethylaminobenzyl alcohol (DMOH) and 4,4'-dimethylamino benzydrol (BZN) . The toxicity, cytotoxicity, and antiseptic action of these activators were first studied . DMOH and BZN presented LD50 values 3-4 times higher than DMT, were less cytotoxic against polymorphonuclear leucocytes, and possessed an antimicrobial character, with a high activity against the most representative microorganisms involved in postoperative infections . The properties of the acrylic bone cements formulated with DMOH and BZN were evaluated to determine the influence of these activators on the curing process and the physicochemical characteristics of the cements . A decrease of the peak temperature was observed for the curing with DMOH or BZN with respect to that of one commercially available formulation (CMW 3) . However, residual monomer content and mechanical properties in tension and compression were comparable to those of CMW 3 . The biocompatibility of acrylic bone cements containing DMOH or BZN was studied and compared with CMW 3 . To that end, intramuscular and intraosseous implantation procedures were carried out and the results were obtained from the histological analysis of the surrounding tissues at different periods of time . Implantation of rods of cement into the dorsal muscle of rats showed the presence of a membrane of connective tissue, which increased in collagen fibers with time of implantation, for all formulations . The intraosseous implantation of the cements in the dough state in the femur of rabbits, revealed a higher and early osseous neoformation, with the presence of osteoid material surrounding the rest of the cured material, for the cement prepared with the activator BZN in comparison with that obtained following the implantation of the cement cured with DMOH or DMT (CMW 3) . Curr Opin Infect Dis, 2003 Aug, 16(4), 327 - 35 Hand hygiene: improved standards and practice for hospital care; Pittet D; PURPOSE OF REVIEW: To review the most recently published literature on hand hygiene practices in healthcare settings . RECENT FINDINGS: Adherence with recommendations for hand hygiene remains low, but key factors of noncompliance have been identified and corrective actions proposed . Current guidelines recommend the use of alcohol-based handrub formulations as the new standard of care, thus requiring a system change in most hospitals . In addition, healthcare worker education and motivation are obviously important to modify hand hygiene behavior and must be part of multimodal strategies to enhance compliance in hospitals . Compliance improvement is associated with reduced infection rates and resistance spread . Handrub application according to recommended practices is an alternative to conventional surgical handscrubbing with antiseptic soap and water for surgical hand preparation . SUMMARY: System change must be addressed in most hospitals where alcohol-based handrubbing has not become a standard of care . Strategies to improve hand hygiene compliance must be multimodal and include staff education and motivation, the use of performance indicators, and hospital management support . Successful campaigns will result in reduced infection rates, antimicrobial resistance spread, and enhance patient safety. J Ethnopharmacol, 2003 Aug, 87(2-3), 163 - 7 Biological activity of extracts from Catalpa bignonioides Walt . (Bignoniaceae); Munoz-Mingarro D et al.; Catalpa bignonioides Walt . (Bignoniaceae) is a species that belongs to a tropical family but has been introduced in many countries as ornamental . Although this plant is consumed by indigenous cultures of South America for medical uses, experimental studies of the biological properties of Catalpa bignonioides are lacking . The aim of this work was to study the biological activity of crude extracts from either pods, seeds or leaves of Catalpa bignonioides which were collected in Spain . Ethyl ether, butanolic and aqueous fractions of the pod extract were also prepared and studied . We have examined the antimicrobial activity against five bacteria and one yeast, the cytotoxic activity against HepG2 cells and the anti-inflammatory and antinociceptive effects in rodents . A preliminary phytochemical analysis of the extracts and fractions was also conducted . Results showed no antimicrobial or antitumoral effects, but prominent anti-inflammatory and antinociceptive actions of the extracts . These last activities may be a result of the presence of either of saponins, sterols or phenols, mainly found in the leaves and pods of the plants.
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