|
|
|
|
|
| Clin Microbiol Infect, 2004 Apr, 10(4), 269 - 71 Does molecular typing make any contribution to the care of patients with infection? Humphreys H. Molecular typing has been used extensively to study the epidemiology of infection, but there are few studies on the role of typing in the clinical management of infected patients . Examples of this include distinguishing relapse of infection from new infection, determining the significance of colonisation with potential pathogens, assessing the capacity of isolates to spread and cause serious illness, and linking changes in antimicrobial resistance with treatment . Further studies in selected patient groups and greater collaboration between molecular microbiologists, clinical microbiologists and infectious disease physicians are required to determine the impact of molecular typing in these and other scenarios. Drugs, 2004, 64(8), 837 - 59 Advances in sepsis therapy; Gluck T et al.; During the past 3 years new insights have been gained into the fundamental elements that underlie the pathogenesis of sepsis, and after years of frustrating failures, progress in the basic understanding of sepsis has translated into successful new therapies . These new treatment strategies have significantly improved the outcome of patients experiencing the puzzling syndrome of severe sepsis . More effective supportive therapies with early, goal-oriented therapy including volume resuscitation, catecholamine therapy and transfusion improve the chances for survival in septic shock . Novel endocrine management with hydrocortisone replacement therapy for relative adrenal insufficiency in septic shock patients and strict blood glucose control provide a survival advantage in critically ill patients . Administering appropriate antimicrobial therapy, nutritional support and ventilation protocols with low tidal volumes have now been shown to benefit septic patients . Finally, human recombinant activated protein C (drotrecogin alfa), which ameliorates sepsis-induced disseminated intravascular coagulation and exerts several other favourable effects on endothelial cells, has been shown to reduce mortality in patients with severe sepsis . On the basis of newly discovered pathophysiological mechanisms of sepsis, several other adjuvant therapies for sepsis are in various stages of preclinical and clinical development . Individualised and optimal supportive care with efforts to reverse the precipitating cause of sepsis remains the mainstay of therapy for severe sepsis . How these new and often expensive regimens will fit into the standard treatment approach to sepsis remains to be defined by future clinical investigations. Biotechnol Prog, 2004 Mar-Apr, 20(2), 426 - 42 A dynamic mathematical model to clarify signaling circuitry underlying programmed cell death control in Arabidopsis disease resistance; Agrawal V et al.; Plant cells undergo programmed cell death in response to invading pathogens . This cell death limits the spread of the infection and triggers whole plant antimicrobial and immune responses . The signaling network connecting molecular recognition of pathogens to these responses is a prime target for manipulation in genetic engineering strategies designed to improve crop plant disease resistance . Moreover, as alterations to metabolism can be misinterpreted as pathogen infection, successful plant metabolic engineering will ultimately depend on controlling these signaling pathways to avoid inadvertent activation of cell death . Programmed cell death resulting from infection of Arabidopsis thaliana with Pseudomonas syringae bacterial pathogens was chosen as a model system . Signaling circuitry hypotheses in this model system were tested by construction of a differential-equations-based mathematical model . Model-based simulations of time evolution of signaling components matched experimental measurements of programmed cell death and associated signaling components obtained in a companion study . Simulation of systems-level consequences of mutations used in laboratory studies led to two major improvements in understanding of signaling circuitry: (1) Simulations supported experimental evidence that a negative feedback loop in salicylic acid biosynthesis postulated by others does not exist . (2) Simulations showed that a second negative regulatory circuit for which there was strong experimental support did not affect one of two pathways leading to programmed cell death . Simulations also generated testable predictions to guide future experiments . Additional testable hypotheses were generated by results of individually varying each model parameter over 2 orders of magnitude that predicted biologically important changes to system dynamics . These predictions will be tested in future laboratory studies designed to further elucidate the signaling network control structure. Folia Microbiol (Praha), 2003, 48(6), 731 - 5 Susceptibility of Escherichia coli to C2-C18 fatty acids; Marounek M et al.; The antimicrobial activity of C2-C18 fatty acids was determined in vitro in cultures of two strains of Escherichia coli grown on glucose . Antimicrobial activity was expressed as IC50 (a concentration at which only 50% of the initial glucose in the cultures was utilized) . Utilization of glucose was inhibited by caprylic acid (IC50 0.30-0.85 g/L) and capric acid (IC50 1.25-2.03 g/L) . Neither short-chain fatty acids (C2-C6) nor fatty acids with longer chain (C12-C18) influenced substrate utilization . Caproic acid, however, decreased cell yield in cultures of E . coli in a dose-dependent manner . No inhibition of glucose utilization was produced with unsaturated fatty acids, oleic and linoleic . Calcium ions added in excess reversed the antimicrobial effect of capric acid, but not that of caprylic acid . Antimicrobial activity of caprylic and capric acid decreased when the bacteria were grown in the presence of straw particles, or repeatedly subcultured in a medium containing these compounds at low concentrations . Counts of viable bacteria determined by plating decreased after incubation with caprylic and capric acid (30 min; 1 g/L) at pH 5.2 from > 10(9) to approximately 10(2)/mL . A reduction of a mere 0.94-1.96 log10 CFU was observed at pH 6.5-6.6 . It can be concluded that caprylic acid, and to a lesser extent also capric acid, has a significant antimicrobial activity toward E . coli . Effects of other fatty acids were not significant or absent. Folia Microbiol (Praha), 2003, 48(6), 709 - 24 Nonmammalian vertebrate antibiotic peptides; Sima P et al.; With the exception of cyclostomes, all vertebrates share the common immune strategy of adaptive, highly specific immunity, based on the products of recombination-activating genes and recombined noninherited receptors for antigens . In addition, they have retained ancient vectors of innate immunity, such as antimicrobial peptides, which are widespread in all eukaryotic organisms and show a high degree of structural homology across most animal taxa . Recently, these substances have become the objects of intensive study for their outstanding bioactive properties with the aim to be applied as very efficient antibiotics, antimicrobials, and even cancerostatics in clinical practice. Przegl Lek, 2003, 60(11), 710 - 5 {The effect of antiinflammatory therapy with dexamethasone and dexamethasone with pentoxifylline on the course of bacterial meningitis}; Bociaga-Jasik M et al.; Despite of antimicrobial therapy mortality rate in the bacterial meningitis (BM) is high . The aim of the study was to assess the influence of anti-inflammatory treatment with dexamethasone and dexamethasone with pentoxifylline on the course of this disease and concentration of proinflammatory cytokines TNF-alpha, IL-1 beta, II-8 in the cerebrospinal fluid (CSF) . 42 patients with the BM were analysed . They were divided into three groups on the basis of applied therapy: A--treated only with antibiotics, A+D--treated with antibiotics and dexamethasone, A+D+P--treated with antibiotics, dexamethasone and pentoxifylline . Anti-inflammatory therapy did not have impact on the resolution of inflammation (pleocytosis, protein and glucose level) in the CSF . However, it was established that adjuvant treatment with dexa-methasone and pentoxifylline has beneficial effect on the course of the BM . In this group 61.5% of patients recovered, in comparison with 28.6% in the group A+D and 26.7% in the group A . Mortality rate was: in the group A--33%, A+D--21.4%, A+D+P--7.7% (p = 0.01) . Correlation between the outcome of the BM in the investigated groups and cytokines concentration in CSF was observed . In the group A+D+P all patients responded to the therapy with decrease of cytokine concentration, and coefficients of variation were low (TNF-alpha--1%, IL-1 beta--23.6%, IL-8--18.9%) . Also in the group A+D decrease of cytokines concentration in the CSF was observed, however was not such significant in all cases . In the group of patients treated only with antibiotics concentration of cytokines in the CSF varied, even increased in some of them . Our investigation indicates that inhibition of cytokines production in central nervous system (CNS) with dexamethasone and pentoxifylline improves the outcome of BM and is associated with the reduction of neurological sequels and deaths. Acta Neurochir (Wien), 2004 Apr, 146(4), 411 - 4; discussion 414 Epub 2004 Feb 16. Nocardia brain abscess mimicking brain tumour in immunocompetent patients: report of two cases and review of the literature; Menku A et al.; Nocardia brain abscess is a rare intracranial lesion and has been reported in immunocompromised patients . An optimal treatment approach has not been established . However, early diagnosis and appropriate antimicrobial therapy are very important factors for a good outcome . We report two unusual cases of Nocardia brain abscess simulating brain tumour in immunocompetent patients . One of the cases was presumed to be a primary brain tumour and the other a metastatic brain tumour . They underwent surgical gross total resection . After Nocardia asteroides was seen on Gram's stain and subsequently identified by culture, appropriate antibiotic therapy was initiated. Intensive Care Med, 2004 May, 30(5), 976 - 9 Epub 2004 Apr 01. Steady-state plasma and intrapulmonary concentrations of piperacillin/tazobactam 4 g/0.5 g administered to critically ill patients with severe nosocomial pneumonia; Boselli E et al.; OBJECTIVE: To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of piperacillin/tazobactam (P/T) administered to critically ill patients with severe bacterial pneumonia . DESIGN: Prospective, open-label study . SETTING: An intensive care unit and research ward in a university hospital . PATIENTS: Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation . INTERVENTIONS: All subjects received a 30-min intravenous infusion of P/T 4 g/0.5 g every 8 h . The steady-state plasma and ELF concentrations of P/T were determined by high-performance liquid chromatography . MEASUREMENTS AND MAIN RESULTS: The mean+/-SD steady-state plasma trough, peak, and intermediate concentrations were 8.5+/-4.6 microg/ml, 55.9+/-21.6 microg/ml, and 24.0+/-13.8 microg/ml for piperacillin, and 2.1+/-1.0 microg/ml, 4.8+/-2.1 microg/ml, and 2.4+/-1.2 microg/ml for tazobactam, respectively . The mean+/-SD steady-state intermediate ELF concentrations were 13.6+/-9.4 microg/ml for piperacillin and 2.1+/-1.1 microg/ml for tazobactam, respectively, showing a mean percentage penetration of piperacillin and tazobactam into ELF of 56.8% and 91.3 %, respectively, with a P/T ratio of 6.5:1 . CONCLUSION: Our results show that during the treatment of severe nosocomial pneumonia, a regimen of P/T 4 g/0.5 g every 8 h might provide insufficient concentrations into lung tissue to exceed the MIC of many causative pathogens . This suggests that higher doses of P/T should be administered in order to maximize the antibiotic concentration at the site of infection, or that a second antimicrobial agent should be used in association. Eur J Clin Pharmacol, 2004 May, 60(3), 149 - 53 Epub 2004 Apr 01. Public drug procurement: the lessons from a drug tender in a teaching hospital of a transition country; Milovanovic DR et al.; INTRODUCTION: There are scarce descriptions of hospital drug procurement in the primary literature . The aim of this study was to analyse the drug tender led by a clinical pharmacologist in a 1200-bed university hospital in Serbia, a developing country in socio-economic transition, and to give recommendations for future steps in hospital drug policy . PROCEDURE AND OUTCOMES: Drug tendering was conducted according to the public procurement law from January to April 2003 . Analysis included the method of defined daily doses and anatomical therapeutic chemical classification, as well as minimal tender prices, free market prices, essential drugs and domestic and foreign manufacturers . The drug tender list consisted of 548 products, 1,315,501 pharmaceutical units and 312 drug entities, among which 164 were essential . For purchasing purposes, 479 drug formulations were selected, costing approximately 1.4 million Euros (approximately 10% of hospital budget) . Three-quarters of the expenditure consisted of antimicrobials (29.1%), cytotoxics (28.8%) and intravenous infusions (17.7%) . The top 20 drugs consumed 62.2% of the total drug expenditure . Competition for the most expensive and/or most used drugs was the key for financial success of applicants, even when they offered a limited number of drugs . The tender achieved 4.6% and 17.2% cost savings in comparison with minimal tender price and free-market price, respectively . The tender did not provide a fair balance between domestic and foreign manufacturers . CONCLUSION: The drug tender is resource-consuming, laborious, and risky job . Aggregation of individual tenders, on a national level and/or regional ones, is probably the best choice for hospitals in transition countries at this time. Mem Inst Oswaldo Cruz, 2004 Feb, 99(1), 107 - 10 Epub 2004 Mar 31. Antimicrobial susceptibility determined by the E test, Löwenstein-Jensen proportion, and DNA sequencing methods among Mycobacterium tuberculosis isolates discrepancies, preliminary results; Freixo MI et al.; Mycobacterium tuberculosis strains resistant to streptomycin (SM), isoniazid (INH), and/or rifampin (RIF) as determined by the conventional Lowenstein-Jensen proportion method (LJPM) were compared with the E test, a minimum inhibitory concentration susceptibility method . Discrepant isolates were further evaluated by BACTEC and by DNA sequence analyses for mutations in genes most often associated with resistance to these drugs (rpsL, katG, inhA, and rpoB) . Preliminary discordant E test results were seen in 75% of isolates resistant to SM and in 11% to INH . Discordance improved for these two drugs (63%) for SM and none for INH when isolates were re-tested but worsened for RIF (30%) . Despite good agreement between phenotypic results and sequencing analyses, wild type profiles were detected on resistant strains mainly for SM and INH . It should be aware that susceptible isolates according to molecular methods might contain other mechanisms of resistance . Although reproducibility of the LJPM susceptibility method has been established, variable E test results for some M . tuberculosis isolates poses questions regarding its reproducibility particularly the impact of E test performance which may vary among laboratories despite adherence to recommended protocols . Further studies must be done to enlarge the evaluated samples and looked possible mutations outside of the hot spot sequenced gene among discrepant strains. Clin Orthop, 2004 Mar, (420), 63 - 71 Treatment of the infected hip replacement; Hanssen AD et al.; Selection of the suitable treatment method for an infected hip arthroplasty requires careful assessment of patient-related variables and expected treatment goals . The basic treatment options include antibiotic suppression, open debridement, resection arthroplasty, arthrodesis, reimplantation of another prosthesis, and amputation . Successful treatment of infection requires complete debridement of all infected and foreign material and appropriate antimicrobial therapy . When possible, the preferred treatment approach is insertion of another prosthesis with a delayed reconstructive treatment technique . Patients now are presenting with an increasing incidence of resistant organisms and severe bone loss, which increases the difficulty of treatment. Biosci Biotechnol Biochem, 2004 Mar, 68(3), 571 - 7 Purification, characterization, and sequencing of novel antimicrobial peptides, Tu-AMP 1 and Tu-AMP 2, from bulbs of tulip (Tulipa gesneriana L.); Fujimura M et al.; Novel antimicrobial peptides (AMP), designated Tu-AMP 1 and Tu-AMP 2, were purified from the bulbs of tulip (Tulipa gesneriana L.) by chitin affinity chromatography and reverse-phase high-performance liquid chromatography (HPLC) . They bind to chitin in a reversible way . They were basic peptides having isoelectric points of over 12 . Tu-AMP 1 and Tu-AMP 2 had molecular masses of 4,988 Da and 5,006 Da on MALDI-TOF MS analysis, and their extinction coefficients of 1% aqueous solutions at 280 nm were 3.3 and 3.4, respectively . Half of all amino acid residues of Tu-AMP 1 and Tu-AMP 2 were occupied by cysteine, arginine, lysine, and proline . The concentrations of peptides required for 50% inhibition (IC(50)) of the growth of plant pathogenic bacteria and fungi were 2 to 20 microg/ml . The structural characteristics of Tu-AMP 1 and Tu-AMP 2 indicated that they were novel thionin-like antimicrobial peptides, though Tu-AMP 2 was a heterodimer composes of two short peptides joined with disulfide bonds. J Antimicrob Chemother, 2004 May, 53(5), 848 - 52 Epub 2004 Mar 31. Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis; Pfausler B et al.; OBJECTIVE: The present study was performed to test the ability of fosfomycin to penetrate into the CSF of neurointensive care patients with ventriculostomy-associated ventriculitis . PATIENTS AND METHODS: Six patients requiring neurointensive care monitoring, including extraventricular drainage due to secondary obstructive hydrocephalus, were enrolled into the study . All patients received 8 g of fosfomycin intravenously three times a day over a period of at least 5 days . Concentrations of fosfomycin in the CSF and plasma were measured after single-dose administration and at steady state . RESULTS: Mean values of the fosfomycin area under the time-concentration curves for the dosing interval of 8 h (AUC(8)) were 929 +/- 280 and 225 +/- 131 mg.h/L for plasma and CSF after single-dose administration, respectively (P < 0.03) . The ratios of the AUC(8) for CSF to the AUC(8) for plasma were 0.23 +/- 0.07 after a single dose and 0.27 +/- 0.08 following multiple doses (P > 0.05, not significant) . Additional in vitro experiments have shown that fosfomycin exerts non-concentration-dependent microbial growth inhibition . At steady state, the time above MIC (t > MIC) values were 98%, 92% and 61% for pathogens with MIC values of 8, 16 and 32 mg/L, respectively . CONCLUSION: The present pharmacokinetic study indicates that 8 g of fosfomycin three times per day should provide sufficient antimicrobial concentrations in the CSF for the overall treatment period . Thus, the co-administration of fosfomycin could be useful for the treatment of ventriculitis caused by susceptible pathogens. Immunology, 2004 Apr, 111(4), 391 - 9 Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression; Sela U et al.; Allicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects . However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied . Here, we examined the in-vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites . We found that allicin (20-100 microm) inhibits the SDF-1alpha (CXCL12)-induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down-regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN . Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration . The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down-regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM-1- and FN-specific alpha4beta1-integrin (VLA-4) . The ability of allicin to down-regulate these chemokine-induced and VLA-4-mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases. Biotechnol Lett, 2004 Feb, 26(4), 287 - 91 Antinematodal activity and the mechanism of the antimicrobial peptide, HP (2-20), against Caenorhabditis elegans; Jang SH et al.; The peptide HP (2-20), derived from the N-terminal sequence of Helicobacter pylori ribosomal protein L1 (RPL1), has a nematicidal activity against eggs and worms of Caenorhabditis elegans . Eggs treated with HP (2-20) (69%) has a higher fluorescence intensity with propidium iodide staining, which was similar to that of melittin (82%) but higher than untreated cells (5.7%) . Confocal microscopy showed that the peptides were located in the shell of the eggs and the inner and outer surfaces of the worms . HP (2-20) therefore may exert its antinematodal activity by disrupting the structure of the egg's shell and the cell membrane via pore formation or by direct interaction with the lipid bilayers in a detergent-like manner. Gen Dent, 2003 Mar-Apr, 51(2), 176 - 81; quiz 182-3 The role of the general dentist in periodontal care; Trovato JP; Epidemiologic studies find the rate of periodontal disease in the U.S . to be of sufficient significance that periodontal therapy should not be placed uniquely in the domain of the specialist . It is advisable that periodontal record-keeping and treatment, particularly with nonsurgical techniques including scaling and root planing and subantimicrobial and antimicrobial therapy, become part of the daily routine in the general practitioner's office. Gen Dent, 2003 Sep-Oct, 51(5), 424 - 8 Microbiology and management of periodontal infections; Brook I; The term periodontal disease refers to all diseases that involve the supportive structures of the periodontium . Peridontal diseases commonly begin as a gingivitis and progress to periodontitis . Necrotizing ulcerative gingivitis (NUG) is the most fulminate form of gingivitis . The two main forms of periodontitis are chronic periodontitis (also known as adult periodontitis) and aggressive periodontitis (also known as early onset periodontitis, destructive periodontitis, and juvenile periodontitis) . Gingivitis treatment involves removing dental plaques and maintaining good oral hygiene . Periodontitis therapy should include root debriding, draining the infected root, and surgically resecting inflamed periodontal tissues . Systemic antimicrobials often are indicated in NUG, chronic periodontitis, and aggressive periodontitis . When possible, antimicrobial selection should be based upon culture and susceptibility testing of the subgingival flora. Unfallchirurg, 2004 Apr, 107(4), 325 - 7 {Varicella associated necrotizing fasciitis in a child}; Groger A et al.; We present a rare case of necrotizing fasciitis in an 5-year-old infant with preexisting varicella infection . Initially, the patient showed acute pain and swelling of the left thorax with high inflammatory parameters and varicella-specific skin affections . MRT presented diffuse soft tissue swelling of the left chest consistent with necrotizing fasciitis . After aggressive surgical debridement of necrotic tissue and extirpation of axillary lymph nodes, the clinical course improved under appropriate parenteral antimicrobial therapy using penicillin and clindamycin . In conclusion, necrotizing fasciitis should be suspected in any child with a history of varicella infection and increasing complaints of pain and swelling in an extremity or other body area associated with increasing fever, erythema, lethargy, and irritability . Shock, multiorgan failure, and death will ensue if the diagnosis is not promptly recognized. Parasite Immunol, 2003 Nov-Dec, 25(11-12), 597 - 608 Consumption of L-arginine mediated by Entamoeba histolytica L-arginase (EhArg) inhibits amoebicidal activity and nitric oxide production by activated macrophages; Elnekave K et al.; In this study we discuss the cloning and expression of Entamoeba histolytica arginase (EhArg), an enzyme that catalyses the hydrolysis of L-arginine to L-ornithine and urea . L-norvaline, a competitive inhibitor of E . histolytica L-arginase, inhibits the growth of the parasite, which suggests that the catabolism of L-arginine mediated by EhArg is essential . Nitric oxide (NO) is an antimicrobial agent that inhibits some key enzymes in the metabolism of Entamoeba histolytica . NO is synthesized by activated macrophages from L-arginine, the substrate of NO synthase (NOS-II) . We show that E . histolytica inhibits NO mediated amoebicidal activity of activated macrophages by consuming L-arginine present in the medium. Nahrung, 2004 Feb, 48(1), 69 - 72 Enhanced bactericidal action and masking of allergen structure of soy protein by attachment of chitosan through maillard-type protein-polysaccharide conjugation; Usui M et al.; The soy protein-chitosan conjugate was formed by the Maillard reaction in dry state (relative humidity 65%) at 60 degrees C for 2 weeks to improve the functional properties . The antimicrobial activity of the Maillard-type soy protein-chitosan conjugates enhanced 2-3 times that of soy protein-chitosan mixture . The soy protein-chitosan conjugate showed excellent emulsifying property with the progress of Maillard-type conjugation . The allergenicity of soy protein was greatly decreased by the attachment of chitosan through Maillard reaction . The immonoblotting analysis with patient's sera revealed that soy protein-chitosan conjugate was more effective to mask the allergen structure of soy protein causing from 34 kDa-protein (Gly m Bd 30K) than soy protein-galactomannan conjugate . The Western blotting showed that allergen (34 kDa-protein) was completely masked by soy protein-chitosan conjugation, while it was not completely masked by soy protein-galactomannan conjugation. Life Sci, 2004 Apr 30, 74(24), 3043 - 52 Propyl paraben inhibits voltage-dependent sodium channels and protects cardiomyocytes from ischemia-reperfusion injury; Ji X et al.; The effects of propyl paraben, an antimicrobial preservative, on voltage-dependent sodium current and myocardial ischemia-reperfusion injury were investigated in isolated adult rat cardiomyocytes . Whole cell voltage-clamp recording showed that propyl paraben reversibly blocked the voltage-gated sodium channel both in concentration- and voltage-dependent manners . Propyl paraben (500 microM but not 100 microM) significantly shifted the steady-state inactivation of the sodium channel toward the hyperpolarizing direction at the V(1/2) point . Consistent with the above result, the propidium iodide (PI) uptake test revealed that pretreatment with 500 microM but not 100 microM of propyl paraben significantly reduced cell death induced by 45 min of sustained ischemia followed by 15 h of reperfusion (42.37 +/- 7.01% of cell viability in control and 71.05 +/- 7.06% in the propyl paraben group), suggesting that propyl paraben can protect myocytes from ischemia-reperfusion injury . These results indicate a possible correlation between the inhibition of sodium current and cardioprotection against ischemia-reperfusion injury. Eur J Med Chem, 2004 Mar, 39(3), 267 - 72 Synthesis of some 2-{(benzazole-2-yl)thioacetylamino}thiazole derivatives and their antimicrobial activity and toxicity; Turan-Zitouni G et al.; Some 2-{(benzazole-2-yl)thioacetylamino}thiazole derivatives (III) were synthesized by reacting 4-methyl-2-(chloroacetylamino)thiazole derivatives (I) with benzazol-2-thiole (II) in acetone in the presence of K(2)CO(3) . The chemical structures of the compounds were elucidated by (1)H NMR and FAB(+)-MS spectral data . The prepared compounds were tested for antimicrobial activity and toxicity. Eur J Med Chem, 2004 Mar, 39(3), 249 - 55 Tetrazolo{1,5-a}quinoline as a potential promising new scaffold for the synthesis of novel anti-inflammatory and antibacterial agents; Bekhit AA et al.; Three series of tetrazolo{1,5-a}quinoline derivatives have been synthesized . The first series was synthesized starting by the condensation of tetrazolo{1,5-a}quinoline-4-carboxaldehyde 2 with substituted thiosemicarbazides, followed by cyclization of the resulting thiosemicarbazones 3 with malonic acid in the presence of acetyl chloride to give pyrimidyl derivatives 4a-c . The second series was prepared by the condensation of the latter compounds 4a-c with the selected aromatic aldehydes to afford the arylidene derivatives 5a-f . The third series 7a-c was synthesized by condensation of tetrazolo{1,5-a}quinoline-4-carboxaldehyde 2 with the appropriate acetophenone, followed by cyclocondensation of the formed alpha,beta-unsaturated ketones with thiourea . The newly synthesized compounds were evaluated for their anti-inflammatory and antimicrobial activities . Four compounds were proved to be as active as indomethacin in animal models of inflammation. Bioorg Med Chem, 2004 Apr 15, 12(8), 1955 - 62 Analogues of antifungal tjipanazoles from rebeccamycin; Voldoire A et al.; Analogues of antifungal tjipanazoles were obtained by semi-synthesis from rebeccamycin, an antitumor antibiotic isolated from cultures of Saccharothrix aerocolonigenes . The antiproliferative activities of the new compounds were evaluated in vitro against nine tumor cell lines . The effect on the cell cycle of murine leukemia L1210 cells was examined and the antimicrobial activities against two Gram positive bacteria, a Gram negative bacterium and a yeast were determined . The inhibitory properties toward four kinases and toward topoisomerase I were evaluated . The most cytotoxic compound in the series was a dinitro derivative characterized as a potent topoisomerase I inhibitor. Bioorg Med Chem, 2004 Apr 15, 12(8), 1845 - 52 Synthesis, antimicrobial activity and conformational analysis of novel substituted pyridines: BF(3)-promoted reaction of hydrazine with 2-alkoxy pyridines; Goda FE et al.; Some new 2-alkoxy-3-cyano-4,6-diarylpyridines 3,4 were synthesized by condensation of different alpha,beta-unsaturated ketones 1 with malononitrile 2, followed by cyclization in sodium alkoxide/alcohol system . Lewis acid-catalyzed reaction of 4 with hydrazine afforded the corresponding 1H-pyrazolo{3,4-b}pyridines 5 . The potency of the results as antimicrobial agents has been evaluated . The structure of the newly prepared compounds was assessed by microanalysis, IR and NMR spectra . Molecular mechanics (MM2) and semiemperical (AM1) molecular orbital calculations have been performed for the most biologically active compounds 5b and c to get insight into their molecular structures and to learn more about their stable molecular conformations. Comp Biochem Physiol B Biochem Mol Biol, 2004 Mar, 137(3), 413 - 20 Phospholipase A2 in porifera; Nevalainen TJ et al.; Phospholipase A2 (PLA2) catalytic activity was measured in aqueous extracts of 83 freeze-dried specimens representing 55 marine sponge species collected from the east coast of Australia including the Great Barrier Reef . High levels (>500 u/l) of PLA2 activity (defined as the amount of activity that releases 1 micromol of fatty acid per min) were found in four out of 55 species (7%), moderate activities (100-499 u/l) in 6/55 (11%), low activities (1-99 u/l) in 11/55 (20%) and no PLA2 activity in 34/55 (62%) . Species with high PLA2 activity levels included Cymbastela coralliophila (2118 u/l, specific activity 10,590 u/g of protein), Acanthella cavernosa (1318 u/l, specific activity 2470 u/g), Spirastrella vagabunda (1036 u/l, specific activity 1727 u/g and Theonella swinhoei (567 u/l, specific activity 354 u/g) . It was postulated that poriferan PLA2 may be involved in eicosanoid metabolism and antimicrobial and toxic defence of the animal. Acta Pharm, 2004 Mar, 54(1), 13 - 26 Synthesis and antimicrobial evaluation of naphtho{2,1-b}pyrano{2,3-d}pyrimidine and pyrano{3,2-e}{1,2,4}triazolo{1,5-c}pyrimidine derivatives; Eid FA et al.; Several novel naphtho{2,1-b}pyrano{2,3-d}pyrimidines, pyrano{3,2-e}{1,2,4}triazolo{1,5-c}pyrimidines and their coumarin-3-yl derivatives were synthesized . Some of these derivatives exhibited pronounced antimicrobial activities. J Org Chem, 2004 Apr 2, 69(7), 2251 - 6 Antineoplastic agents 491 . Synthetic conversion of aaptamine to isoaaptamine, 9-demethylaaptamine, and 4-methylaaptamine; Pettit GR et al.; Aaptamine (1) was used as starting material for synthetic transformation to isoaaptamine (2), 9-demethylaaptamine (5), and 4-methylaaptamine (6) . A general method for the selective O-demethylation of such 1H-benzo{de}{1,6}-naphthyridine (1) marine sponge constituents at position C-9 has been developed . Selective O-demethylation of aaptamine (1) and 1-methylaaptamine (11) with 48% hydrobromic acid led to 9-demethylaaptamine (5) and isoaaptamine (2), respectively . A selection of other aaptamine derivatives were synthesized, and their structures were unambiguously determined by X-ray methods . In addition, their cancer cell growth inhibitory properties were evaluated against the murine P388 lymphocytic cell line and a minipanel of human cancer cell lines . Evaluation as inhibitors of the PKC signal transduction pathway and against a selection of microorganisms was also undertaken . Aaptamine derivatives 3 and 5 had broad-spectrum antimicrobial activities. Med Clin North Am, 2004 Mar, 88(2), 483 - 94 Acute and chronic prostatitis; Hua VN et al.; In summary, prostatitis is a complex syndrome that spans a spectrum from acute prostatitis with a straightforward presentation to CP-CPPS with a complex array of symptoms . The identification of prostatic or pelvic pain becomes a requirement for the diagnosis of CP-CPPS . The NIH system of prostatitis categorization is a refinement of the traditional classification of prostatitis by Drach et al, which was based on the localization test of Meares and Stamey . The NIH categorization system allows for a framework to define the disease process, and the NIH-CPSI was created to quantify the symptoms of chronic prostatitis . Integral to the classification of prostatitis is the presence or absence of inflammation, determined by looking for leukocytes in the EPS, seminal fluid, and VB3 specimens . In addition, the role of bacteria as a cause in category III prostatitis continues to be debated . Future research into using inflammatory markers (eg, tumor necrosis factor-alpha, interleukin-2) and using PCR to identify the presence of bacteria may further refine the pathophysiology of prostatitis . The mainstream treatment of chronic prostatitis involves antimicrobials, non-steroidal anti-inflammatory medications, and alpha-blockers . The potential role of asymptomatic category IV chronic prostatitis in the etiology of prostate cancer may be delineated further with future research. Biotechnol Lett, 2004 Feb, 26(3), 185 - 91 Cloning, expression, and biological function of a dTDP-deoxyglucose epimerase (gerF) gene from Streptomyces sp . GERI-155; Sohng JK et al.; GERI-155 is a macrolide antibiotic containing two deoxyhexose molecules which has antimicrobial activities against gram-positive bacteria . The deoxyhexose biosynthetic gene cluster of GERI-155 from Streptomyces sp . GERI-155 genome has now been isolated . Four orf were identified and a putative orf, supposed to code for the dTDP-deoxyglucose epimerase gene, was designated as gerF . gerF was expressed in E . coli using recombinant expression vector pHJ3 . The recombinant protein expressed in a soluble form . The enzyme was purified by Ni-affinity column using imidazole buffer as eluents . The molecular mass of the expressed protein correlated with the predicted mass (36,000 Da) deduced from the cloned gene sequence data . The purified enzyme produced maltol from dTDP-4-keto-6-deoxyglucose and it was confirmed that the expressed protein was dTDP-deoxyglucose epimerase catalyzing epimerization of C-3 and C-5 or C-3 of dTDP-4-keto-6-deoxyglucose. Nat Immunol, 2004 May, 5(5), 488 - 94 Epub 2004 Mar 28. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM; Couillault C et al.; Both plants and animals respond to infection by synthesizing compounds that directly inhibit or kill invading pathogens . We report here the identification of infection-inducible antimicrobial peptides in Caenorhabditis elegans . Expression of two of these peptides, NLP-29 and NLP-31, was differentially regulated by fungal and bacterial infection and was controlled in part by tir-1, which encodes an ortholog of SARM, a Toll-interleukin 1 receptor (TIR) domain protein . Inactivation of tir-1 by RNA interference caused increased susceptibility to infection . We identify protein partners for TIR-1 and show that the small GTPase Rab1 and the f subunit of ATP synthase participate specifically in the control of antimicrobial peptide gene expression . As the activity of tir-1 was independent of the single nematode Toll-like receptor, TIR-1 may represent a component of a previously uncharacterized, but conserved, innate immune signaling pathway. Thorax, 2004 Apr, 59(4), 318 - 23 Linkage of neutrophil serine proteases and decreased surfactant protein-A (SP-A) levels in inflammatory lung disease; Rubio F et al.; BACKGROUND: In patients with cystic fibrosis (CF) neutrophils are recruited in excess to the airways yet pathogens are not cleared and the patients suffer from chronic infections . Recent studies have shown a deficiency in airway fluids from patients with CF and other inflammatory pulmonary conditions of surfactant protein A (SP-A), a pattern recognition molecule that facilitates uptake of microbes by macrophages and neutrophils . METHODS: In vitro simulations were used to test the hypothesis that decreased SP-A levels in CF might be the result of degradation by neutrophil serine proteases . RESULTS: Very low levels of the neutrophil granule serine proteases cathepsin G, elastase, and proteinase-3 rapidly degraded pure SP-A when tested in buffered saline . The order of potency was cathepsin G>elastase>proteinase-3 . The addition of cathepsin G or elastase to normal bronchoalveolar lavage (BAL) fluid caused a dose dependent degradation of endogenous native SP-A . Cathepsin G and elastase were present in the BAL fluid from many patients with CF . Simple incubation of protease positive BAL fluid from patients with CF caused a time dependent degradation of added SP-A or, where present, endogenous SP-A . The degradation of SP-A by protease(s) in BAL fluid of patients with CF was abrogated by diisopropylfluorophosphate and monocyte/neutrophil elastase inhibitor . CONCLUSIONS: The findings strongly suggest that the neutrophil serine proteases cathepsin G and/or elastase and/or proteinase-3 contribute to degradation of SP-A and thereby diminish innate pulmonary antimicrobial defence. Antimicrob Agents Chemother, 2004 Apr, 48(4), 1307 - 12 Antimicrobial and DNA gyrase-inhibitory activities of novel clorobiocin derivatives produced by mutasynthesis; Galm U et al.; Twenty-eight novel clorobiocin derivatives obtained from mutasynthesis experiments were investigated for their inhibitory activity towards Escherichia coli DNA gyrase and for their antibacterial activities towards clinically relevant gram-positive and gram-negative bacteria in comparison to novobiocin and clorobiocin . Clorobiocin was the most active compound both against E . coli DNA gyrase in vitro and against bacterial growth . All tested modifications of the 3-dimethylallyl-4-hydroxybenzoyl moiety reduced biological activity . The highest activities were shown by compounds containing a hydrophobic alkyl substituent at position 3 of the 4-hydroxybenzoyl moiety . Polar groups in this side chain, especially amide functions, strongly reduced antibacterial activity . Replacement of the alkyl side chain with a halogen atom or a methoxy group at the same position markedly reduced activity . Transfer of the pyrrole carboxylic acid moiety from O-3" to O-2" of L-noviose moderately reduced activity, whereas the complete absence of the pyrrole carboxylic acid moiety led to a loss of activity . Desclorobiocin derivatives lacking the chlorine atom at C-8 of the 3-amino-4,7-dihydroxycoumarin moiety also showed low activity . Lack of a methyl group at O-4" of L-noviose resulted in an inactive compound . From these findings it appears that clorobiocin represents a "highly evolved" structure optimized for bacterial transport and DNA gyrase inhibition. Antimicrob Agents Chemother, 2004 Apr, 48(4), 1112 - 7 In vivo detection and quantification of tetracycline by use of a whole-cell biosensor in the rat intestine; Bahl MI et al.; An Escherichia coli biosensor strain, harboring the plasmid pTGFP2, was introduced into the gastrointestinal tract of gnotobiotic rats that continuously received drinking water containing tetracycline . Plasmid pTGFP2 contains a transcriptional fusion between a green fluorescent protein (GFP) gene and a tetracycline-regulated promoter and was shown to produce a proportional GFP signal in response to exposure to various tetracycline concentrations when harbored by an E . coli strain . The plasmid was highly unstable in the host bacteria colonizing the intestinal system of the animals, and rapid plasmid loss was observed . Reintroduction of the E . coli MC4100/pTGFP2 strain into animals already colonized by the plasmid-free E . coli strain the day before euthanasia made it possible to extract and analyze the biosensors from intestinal samples . The induction of GFP in the biosensor cells extracted from the animals was estimated on a single-cell basis by use of flow cytometry, and the mean induction of GFP in the samples was compared to a standard curve prepared from known tetracycline concentrations . The results showed that the bioavailable tetracycline concentration within the bacterial growth habitat of the intestine was proportional to the concentration of tetracycline in drinking water but represented only approximately 0.4% of the intake concentration . This is a significant finding which will help to clarify antimicrobial therapy in the intestinal environment. J Mol Biol, 2004 Apr 9, 337(5), 1073 - 7 The tylosin-resistance methyltransferase RlmA(II) (TlrB) modifies the N-1 position of 23S rRNA nucleotide G748; Douthwaite S et al.; The methyltransferase RlmA(II) (TlrB) confers resistance to the macrolide antibiotic tylosin in the drug-producing strain Streptomyces fradiae . The resistance conferred by RlmA(II) is highly specific for tylosin, and no resistance is conferred to other macrolide drugs, or to lincosamide and streptogramin B (MLS(B)) drugs that bind to the same region on the bacterial ribosome . In this study, the methylation site of RlmA(II) is identified unambiguously by liquid chromatography/electrospray ionization mass spectrometry as the N-1 position of 23S rRNA nucleotide G748 . This position is contacted by the mycinose sugar moiety of tylosin, which is absent from the other drugs . The selective resistance to tylosin conferred by m(1)G748 illustrates how differences in drug structure facilitate the drug fit at the MLS(B)-binding site . This observation is of relevance for the rational design of novel antimicrobials targeting the MLS(B) site, especially if the antimicrobials are to be used against pathogens possessing m(1)G748. Res Vet Sci, 2004 Jun, 76(3), 195 - 8 In vitro susceptibility of field isolates of Francisella tularensis subsp . holarctica recovered in Spain to several antimicrobial agents; Garcia del Blanco N et al.; Forty-two recent (1997-1999) Spanish isolates of Francisella tularensis subsp.holarctica were tested in a broth microdilution method for their susceptibilities to 29 antimicrobial agents, including penicillins, cephalosporins, cephamicins, monobactams, penems, aminoglycosides, tetracyclines, macrolides, quinolones, chloramphenicol and fosfomycin . The isolates were resistant to beta-lactam antibiotics and susceptible to chloramphenicol, ciprofloxacin, levofloxacin and norfloxacin. Berl Munch Tierarztl Wochenschr, 2004 Mar-Apr, 117(3-4), 81 - 7 {Antimicrobial susceptibility testing of bacteria isolated from animals: considerations concerning the predefinition of breakpoints from the clinical pharmacological viewpoint}; Kietzmann M et al.; In vitro susceptibility tests are performed to receive information for selecting the most suitable antibacterial agent . As result of in vitro susceptibility tests, the minimum inhibitory concentration (MIC) indicates bacteria as resistant or sensitive . To determine MIC, therapeutically relevant breakpoints have to be defined . Microbiological criteria, chemical and physical characteristics as well as pharmacokinetic and toxicological (tolerance) properties of the antimicrobial compounds have to be considered in the selection of the therapeutic agent in addition to clinical experiences . Using some concentration and time dependent antibiotics as examples, it is demonstrated that the above mentioned criteria are not sufficiently considered in currently defined breakpoints. Intensive Care Med, 2004 Jun, 30(6), 1089 - 96 Epub 2004 Mar 26. Surveillance of antimicrobial use and antimicrobial resistance in intensive care units (SARI): 1 . Antimicrobial use in German intensive care units; Meyer E et al.; OBJECTIVE: To study antimicrobial use for benchmarking and ensuring quality of antimicrobial treatment and to identify risk factors associated with the high use of antimicrobials in German intensive care units (ICUs) through implementation of the SARI (Surveillance of Antimicrobial Use and Antimicrobial Resistance in ICUs) system . DESIGN: Prospective, unit-based surveillance on antimicrobial use from February, 2000, until June, 2002 . The data are standardised by use of the defined daily dose (DDD) for each antimicrobial defined by the WHO and by calculating use per 1000 patient days . SETTING: The data were obtained from 35 German ICUs and stratified by type of ICU (medical, surgical, interdisciplinary) . RESULTS: To date, the project covers a total of 266,013 patient days in 744 reported ICU months and 354,356 DDDs . Mean antimicrobial use density (AD) was 1,332 DDD/1000 patient days and was correlated with length of stay . Penicillins with beta-lactamase inhibitor (AD 338.3) and quinolones (155.5) were the antimicrobial group with the highest ADs . Comparison with US ICARE (Intensive Care Antimicrobial Resistance Epidemiology)/AUR (Antimicrobial Use and Resistance) data revealed a higher AD for glycopeptides and 3rd generation cephalosporins in ICARE/AUR ICUs, but a higher AD for carbapenems in German SARI ICUs regardless of the type of ICU . In the multivariate analysis, length of stay was an independent risk factor for an AD above the 75% percentile of the total amount of antimicrobials used (OR 1.96 per day); likewise, for the AD above the 75% percentile of carbapenems (OR 1.90 per day) and penicillins with extended spectrum (OR 2.01 per day) . High use of glycopeptides and quinolones (AD >75% percentile) correlated with central venous catheter (CVC) rate (OR 1.14 per CVC day per 100 patient days and 1.16, respectively) . CONCLUSION: The SARI data on antimicrobials serve ICUs as a benchmark by which to improve the quality of antimicrobial drug administration and for international comparison. Can Respir J, 2004 Mar, 11(2), 131 - 7 Inpatient care of community-acquired pneumonia: the effect of antimicrobial guidelines on clinical outcomes and drug costs in Canadian teaching hospitals; Marras TK et al.; BACKGROUND: Evidence supporting antibiotic treatment guidelines and respiratory quinolones (RQs) in community-acquired pneumonia (CAP) is limited . OBJECTIVE: To study associations among guideline adherence, specific antibiotics, clinical outcomes and antibiotic costs . METHODS: A retrospective cohort study in three tertiary care university teaching hospitals in Toronto, Ontario, studying CAP inpatients between November 1997 and June 2000 . The period encompassed 12 months when an early version of empirical antibiotic guidelines was used (early cohort) and 18 months when recent guidelines (including RQs) were used (recent cohort) . RESULTS: Six hundred ninety-eight cases of CAP were reviewed, and 91% were guideline adherent . In multivariable analyses, no association was observed between guideline adherence and mortality or duration of hospitalization . Guideline-adherent cases received fewer antibiotics in both cohorts and 0.9 days less of intravenous antibiotics (P=0.04) in the recent cohort . There was no significant difference in antibiotic cost according to guideline adherence, but recent cohort guideline-adherent cases had lower drug costs than early cohort guideline-adherent cases . Antibiotic selection was associated with illness severity and was mirrored by clinical outcomes, despite controlling for the pneumonia severity index (PSI) . Treatment with anaerobic agents (odds ratio 2.7, P=0.001) or cephalosporin plus macrolide (odds ratio 2.7, P=0.02) was associated with higher mortality . Treatment with RQ monotherapy was associated with a 2.3 day shorter duration of intravenous therapy (P<0.0001) and a 19.19 dollars lower total antibiotic cost (P<0.0001) . CONCLUSION: Findings support empirical treatment guidelines for CAP and their recommendations regarding RQs . The association between mortality and anaerobic coverage or combination therapy may reflect prognostic information available at presentation but not captured by the PSI. J Dent Res, 2004 Apr, 83(4), 333 - 7 Expression of adrenomedullin and its receptors in human salivary tissue; Kapas S et al.; Adrenomedullin is a multifunctional peptide produced by a wide range of different cells and tissues . This study was designed to investigate whether adrenomedullin is present in human saliva and in salivary glands . It was expected that saliva may contain high concentrations of adrenomedullin, which has antimicrobial activity in vitro, which may have functional implications in the oral cavity . Saliva from the submandibular and parotid glands contained higher concentrations of adrenomedullin than did the circulation, but lower concentrations than in whole saliva . This suggests that oral epithelium may contribute the majority of the adrenomedullin peptide found in saliva . Specific adrenomedullin receptors were found in cell lines from the submandibular (HSG) and parotid (HSY) salivary glands . These findings suggest a paracrine/autocrine role for adrenomedullin in these tissues; however, the concentration of adrenomedullin in saliva was insufficient to suggest a significant antimicrobial action in the healthy oral cavity. J Antimicrob Chemother, 2004 May, 53(5), 832 - 6 Epub 2004 Mar 24. Efficacy of allicin, the reactive molecule of garlic, in inhibiting Aspergillus spp . in vitro, and in a murine model of disseminated aspergillosis; Shadkchan Y et al.; OBJECTIVES: The evaluation of allicin, the biologically active compound responsible for the antimicrobial activities of freshly crushed garlic cloves, in inhibiting Aspergillus spp . in vitro and in a murine model of disseminated aspergillosis . METHODS: Pure allicin was prepared by reacting synthetic alliin with a stabilized preparation of the garlic enzyme alliinase . We tested the in vitro efficacy of pure allicin against 31 clinical isolates of Aspergillus spp . using a microdilution broth method and following the NCCLS guidelines (document M-38P) . Subsequently, the in vivo efficacy of allicin was tested in immunocompetent mice infected intravenously (iv) with Aspergillus fumigatus conidia . Allicin (5 mg/kg body weight) was administered iv once daily for 5 days post-infection or orally (po) (9 mg/kg body weight) for 5 days pre-infection and 10 days post-infection . No ill effects were observed in allicin-treated uninfected mice . RESULTS: The in vitro MICs and MFCs of allicin were between 8 and 32 mg/L, indicating that allicin in its pure form may be an effective fungicide in vitro . Time-kill studies indicate that allicin exerts its fungicidal activity within 2-12 h of administration in vitro . Allicin treatment significantly prolonged survival of infected mice (P < 0.01) from mean survival time (MST) = 7.7 days in untreated mice to MST = 21.3 and 13.9 days for allicin iv and po treated mice, respectively . Allicin iv treatment led to a significant (P < 0.001) 10-fold reduction in fungal burden in A . fumigatus infected mice as evaluated by quantitative fungal cultures of kidney tissue samples . CONCLUSIONS: These favourable results, despite the short half-life of this compound in vivo, support further studies of controlled sustained release or more prolonged administration of allicin as a treatment for aspergillosis. Am J Respir Crit Care Med, 2004 Jul 15, 170(2), 133 - 40 Epub 2004 Mar 24. Effects of interferon-gamma 1b on biomarker expression in patients with idiopathic pulmonary fibrosis; Strieter RM et al.; In a recent study of IFN-gamma 1b in 330 patients with idiopathic pulmonary fibrosis (IPF), progression-free survival was unchanged; however, a trend toward lower mortality was seen in IFN-gamma 1b-treated patients compared with placebo-treated patients (9.9 vs . 16.7%; p = 0.08) . The purpose of this randomized, double-blind, placebo-controlled trial was to characterize molecular effects of subcutaneous IFN-gamma 1b (200 microg) thrice weekly for 6 months versus placebo in 32 patients with IPF . Messenger RNA in transbronchial lung biopsies and bronchoalveolar lavage cell pellet and protein levels in bronchoalveolar lavage fluid (BALF) and plasma were evaluated . After IFN-gamma 1b treatment, IFN-inducible T cell-alpha chemoattractant/CXCL11 (a chemokine with immunomodulatory, antiangiogenic, and defensin-like antimicrobial properties) increased in BALF (p = 0.016) and plasma (p < 0.001); BALF levels of epithelial neutrophil-activating protein-78/CXCL5 (p = 0.054), platelet-derived growth factor A (p = 0.033), and Type I procollagen (p = 0.096) were lower; and IFN-gamma levels were higher (p = 0.093) versus placebo . For messenger RNA in transbronchial biopsies, trends (p > 0.05 and <or= 0.10) associated with IFN-gamma 1b treatment included an increase in IFN-inducible T cell-alpha chemoattractant/CXCL11, a decrease in elastin, and smaller increases for Type III procollagen and platelet-derived growth factor B . Changes in biomarkers of fibrosis, angiogenesis, proliferation, immunomodulation, and antimicrobial activity suggest that IFN-gamma 1b may affect IPF through multiple pathways. Dev Comp Immunol, 2004 Jun, 28(7-8), 747 - 54 Organization and expression analysis of the zebrafish hepcidin gene, an antimicrobial peptide gene conserved among vertebrates; Shike H et al.; Hepcidin is an antimicrobial peptide and iron-regulatory molecule that is conserved among vertebrates . Mutations or over-expression of the human hepcidin gene have been found in patients with hemochromatosis and refractory anemia . To further understand the function and regulation of hepcidin, animal models are needed . We sequenced cDNA, genes and upstream regions of zebrafish hepcidin and analyzed gene expression by kinetic PCR . Zebrafish hepcidin genes consist of two introns and three exons that encode a prepropeptide (91 amino acids) . The amino acid sequences and gene organization were remarkably conserved between zebrafish and other species . Elevated gene expression was observed in abdominal organs, skin, and heart in fish that developed signs of infection following bacterial injection . Zebrafish may be a suitable model organism for further study of hepcidin gene regulation. Dev Comp Immunol, 2004 Jun, 28(7-8), 701 - 11 Effect of experimental microbial challenge on the expression of defense molecules in Eisenia foetida earthworm; Kohlerova P et al.; Earthworms are able to protect themselves against invading pathogens due to efficient innate defense mechanisms . Currently, two types of antimicrobial factors including lysozyme-like molecule and factors with hemolytic activity, as well as a pattern recognition protein named coelomic cytolytic factor (CCF) have been identified in Eisenia foetida earthworms . However, the modulations of these defense molecules during in vivo immune response have not been addressed . In this study, we investigated the effect of experimental challenge with live Gram-negative and Gram-positive bacteria and with beta-1,3-glucan on the expression of CCF and the hemolytic factor fetidin . In parallel, we followed levels of hemolytic activity and lysozyme-like activity in the coelomic fluid of challenged earthworms . We show that the biosynthesis of CCF, but not fetidin, is up-regulated upon microbial stimulation . Parenteral administration of bacteria or microbial polysaccharides in earthworms results, in the coelomic fluid, in augmented level of CCF, increased lysozyme-like activity and decreased hemolytic activity . The decreased hemolytic activity of the coelomic fluid reflects the increase of the whole protein content in the absence of synthesis of hemolytic proteins. J Nat Prod, 2004 Mar, 67(3), 506 - 9 Antineoplastic agents . 380 . Isolation and X-ray crystal structure determination of isoaaptamine from the Republic of Singapore Hymeniacidon sp . and conversion to the phosphate prodrug hystatin 1; Pettit GR et al.; By use of bioassay (murine P388 lymphocytic leukemia cell line) guided isolation procedures, extracts of the Republic of Singapore marine sponge Hymeniacidon sp . were found to contain demethyloxyaaptamine (1) and aaptamine (3) as prominent cancer cell growth inhibitory constituents accompanied by the trace, albeit more active, component isoaaptamine (4) . The isolation, X-ray structure elucidation, and antineoplastic and antimicrobial activities of isoaaptamine (4) have been summarized . Because of instability, isoaaptamine (4) was converted to a stable sodium phosphate prodrug designated hystatin 1 (7). Nucleosides Nucleotides Nucleic Acids, 2004, 23(1-2), 317 - 37 Synthesis of azole nucleoside 5'-monophosphate mimics (P1Ms) and their inhibitory properties of IMP dehydrogenases; Wang G et al.; IMPDH inhibitors have potential antimicrobial, anticancer and immunomodulatory effects . Nucleoside inhibitors of IMPDH exert their inhibitory effects via nucleoside 5'-MPs . Conversion of nucleoside analogs to NMPs by cellular nucleoside kinases is not assured, and usually is inefficient . In order to bypass cellular phosphorylation, a series of azole nucleoside 5'-MP mimics (P1Ms) based on ribavirin, EICAR and bredinin were synthesized and screened against human and C . albicans IMP dehydrogenises . P1Ms 8, 16, 25, 28 and 29 demonstrated substantial IMPDH inhibition with Ki values in low micromolar range. Presse Med, 2004 Mar 13, 33(5), 327 - 9 {Treatment with oral antibiotics of febrile neutropenia in onco-haematology . The experience of the EORTC antimicrobial group}; Cometta A et al.; THE CONTEXT: Up until the nineties, the intravenous administration of a broad spectrum antibiotic was the classical treatment of any patient presenting with febrile neutropenia . Since then, in patients considered at low risk and with expected of neutropenia less than 7-10 days, oral antibiotherapy has become an attractive option . TWO LARGE STUDIES: A study by the antimicrobial group of the EORTC (European organisation for research and treatment of cancer) and a North American study have compared the efficacy of an oral combination of ciprofloxacine and amoxicillin/clavulanic acid with that of an intravenous antibiotherapy in low-risk patients presenting febrile neutropenia . In both studies, the success rate was the same in the group of patients treated with oral antibiotics and those treated with intravenous antibiotics . RESERVATIONS: These two studies were conducted in hospitalised patients . No conclusions can be drawn with regard to out-patient treatment . Out-patient management would only be possible after appropriate selection of patients at low risk. J Inorg Biochem, 2004 Apr, 98(4), 601 - 15 Syntheses, crystal structures and antimicrobial activities of monomeric 8-coordinate, and dimeric and monomeric 7-coordinate bismuth(III) complexes with tridentate and pentadentate thiosemicarbazones and pentadentate semicarbazone ligands; Nomiya K et al.; Novel bismuth(III) complexes 1-4 with the tridentate thiosemicarbazone ligand of 2N1S donor atoms {Hmtsc (L1); 2-acetylpyridine (4N-morpholyl thiosemicarbazone)}, the pentadentate double-armed thiosemicarbazone ligand of 3N2S donor atoms {H2dmtsc (L3); 2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone)} and the pentadentate double-armed semicarbazone ligand of 3N2O donor atoms {H2dasc (L4b); 2,6-diacetylpyridine bis(semicarbazone)}, were prepared by reactions of bismuth(III) nitrate or bismuth(III) chloride and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FTIR and NMR (1H and 13C) spectroscopy . The crystal and molecular structures of complexes 1, 2a, 2b and 4b, and the "free" ligand L1 were determined by single-crystal X-ray structure analysis . The dimeric 7-coordinate bismuth(III) complex {Bi(dmtsc)(NO3)}2, 1, and the monomeric 7-coordinate complexes {Bi(Hdasc)(H2O)}(NO3)2.H2O (major product), 2a, and {Bi(dasc)(H2O)}NO3.H2O (minor product), 2b, all with pentagonal bipyramidal bismuth(III) centers, are depicted with one electron pair (6s2) of the bismuth(III) atom, deprotonated forms of multidentate thiosemicarbazone or semicarbazone ligands, and monodentate NO3 or H2O ligands, respectively . These complexes are related to the positional isomers of one electron pair of the bismuth(III) atom; 1 has an electron pair positioned in the pentagonal plane (basal position), while 2a and 2b have an electron pair in the apical position . The monomeric 8-coordinate complex {Bi(mtsc)2(NO3)}, 4b, which was obtained by slow evaporation in MeOH of the 1.5 hydrates 4a, was depicted with one electron pair of the bismuth(III) atom, two deprotonated mtsc- ligand and one nitrate ion . On the other hand, crystals of the complex "{Bi(mtsc)Cl2}", 3, prepared by a reaction of BiCl3 with L1 showed several polymorphs (3a, 3b, 3c and 3d) due to coordination and/or solvation of dimethyl sulfoxide (DMSO) used in the crystallization . Bismuth(III) complexes 1 and 4a showed selective and effective antibacterial activities against Gram-positive bacteria . The structure-activity relationship was discussed. Clin Ther, 2004 Feb, 26(2), 271 - 81 Effects of blood loss and fluid volume replacement on serum and tissue gentamicin concentrations during colorectal surgery; Markantonis SL et al.; BACKGROUND: The prophylactic administration of antimicrobial agents to surgical patients has become standard practice to minimize the risk for postsurgical infection . During surgery, factors such as renal clearance, fluid administration, and blood loss contribute to drug concentrations achieved in the blood and tissues . The aminoglycoside gentamicin was chosen to investigate these factors because it is used for standard antimicrobial prophylaxis in colorectal surgery . OBJECTIVE: The aim of this study was to investigate the effects of surgical blood loss and fluid volume replacement on gentamicin concentrations in serum and in 3 tissue types (subcutaneous fat, epiploic fat, and colonic wall) in patients undergoing colorectal surgery . METHODS: This uncontrolled, open-label study was conducted at the Aretaieion Hospital (Athens, Greece) between November 2002 and March 2003 . Patients selected for this study were scheduled to undergo elective colorectal surgery of ? 2-hour duration with general and epidural anesthesia and to receive gentamicin as major antimicrobial prophylaxis . Blood and tissue samples were obtained concurrently at specific times throughout each procedure . The effect of intraoperative blood loss on gentamicin concentrations and its pharmacokinetic properties was determined . RESULTS: Sixteen patients completed the study (11 men, 5 women; white race, 16 patients {100%}; mean {SD} age, 61 {3} years {range, 39-80 years}) . Mean (SEM) serum gentamicin concentration was found to be insufficient; the maximum plasma drug concentration/minimum inhibitory concentration (MIC) ratio was <8:1 for pathogens commonly isolated in the surgical unit of the hospital (MIC: 1-4 microg/mL) . The mean (SEM) concentration at first surgical incision was 7.83 (0.82) microg/mL and decreased to 2.60 (0.28) microg/mL at skin closure, resulting in borderline effectiveness even for susceptible gram-positive microorganisms (MIC approximately 1.0) . Initially, mean (SEM) tissue gentamicin concentrations in subcutaneous fat, epiploic fat, and colonic wall were low (2.02 {0.34} microg/mL, 2.41 {0.42} microg/mL, and 1.93 {0.38} microg/mL, respectively) and decreased approximately 1.0 microg/mL ( approximately 50%) by skin closure . Statistically significant positive correlations were found between gentamicin concentrations in serum and tissues (P </= 0.03) . A strong negative correlation was found between the intravenously administered fluids and gentamicin concentrations in serum and tissues (P </= 0.04) . CONCLUSIONS: In this study, the administration of a 2-mg/kg dose of gentamicin as antimicrobial prophylaxis during colorectal surgery associated with significant intraoperative blood loss and therefore requiring significant fluid replacement did not achieve concentrations of the drug above MICs for gram-negative microorganisms throughout the procedures in either serum or tissue samples. Arzneimittelforschung, 2004, 54(2), 119 - 24 Synthesis and preliminary antimicrobial evaluation of new 7-(N-pyrrolyl) derivatives of cephalosporins; Bijev A et al.; A series of seven new cephalosporins was prepared for preliminary microbiological evaluation by N-acylation of 7-aminocephalosporanic acid with substituted N-pyrrolylcarboxylic acids via mixed anhydrides . The chemical structure of the compounds were confirmed by IR, 1H-NMR and mass spectral data . The 7-(N-pyrrolyl) cephalosporin derivatives were tested in vitro by the disc diffusion method upon 3 strains and subsequent determination of the minimal inhibitory concentration (MIC) of the most active ones upon 29 strains . The products of the series exhibited antibacterial activity . They showed selective potency against gram-positive and were practically inactive against gram-negative microorganisms . The compound 3-{(acetyloxy)methyl}-7-({2-{3-(ethoxycarbonyl)-2-methyl-5-phenyl-1H-1-pyrrolyl}acetyl}amino)-6-oxo-7,7a-dihydro-2H,6H-aceto{2,1-b}{1,3}thiazine-4-carboxylic acid (4a) was outlined as more active than the reference cefazolin (CAS 23325-78-2) in regard to S . pyogenes and some strains of S . aureus, the MIC of 4a against S . pyogenes were at least 4-fold lower . The toxicological evaluations of the starting N-pyrrolylcarboxylic acids showed no acute toxicity. Nippon Rinsho, 2004 Mar, 62(3), 489 - 94 {Second-line eradication therapy for H . pylori infection}; Murakami K et al.; The widespread use of eradication therapy for Helicobacter pylori has lead to an increase in antibiotic-resistant strains and the problem of retreatment in cases of eradication failure . Retreatment in cases of eradication failure has achieved relatively good results with regimens containing bismuth compounds and tetracyclines in the world, but consensus has not been reached in Japan and each institution has its own policy . An triple therapy consisted of proton pump inhibitor, amoxicillin and metronidazole has been reported to show a good cure rate as a second line therapy in Japan, but metronidazole has not been approved by the Japanese regulatory authority for use against bacterial infections, including H . pylori, despite its worldwide use as an antimicrobial agent in H . pylori eradication regimens. Arch Pharm (Weinheim), 2004 Mar, 337(3), 140 - 7 Synthesis and antimicrobial evaluation of some novel cholestane heterocyclic derivatives; Elmegeed GA et al.; This study was performed to investigate the reactivity of 5alpha-cholestan-3-one (1) towards various chemical reagents to produce new steroidal heterocyclic derivatives . The aminothieno{2, 3:2, 3}cholestane derivative 2 was synthesized according to Gewald's conditions . The diazonium salt of compound 2 coupled with malononitrile to afford dicyanomethylenhydrazinothieno{2', 3':2, 3}cholestane derivative 5 . The behavior of compound 5 towards nitrogen nucleophiles and several active methylene reagents was investigated . Additionally, a variety of steroidal heterocyclic derivatives like compounds 15a, b-22a, b were synthesized starting with 5alpha-cholestan-3-one (1) . The structures of the compounds were established based on the analytical and spectral data . The in vitro antimicrobial activity of some newly synthesized compounds against bacteria and fungi was studied. AJNR Am J Neuroradiol, 2004 Mar, 25(3), 395 - 401 Neurobrucellosis: clinical and neuroimaging correlation; Al-Sous MW et al.; BACKGROUND AND PURPOSE: Manifestation of nervous system involvement by neurobrucellosis, a treatable infection, is not well documented . We investigated patterns of nervous system involvement and determined if neuroimaging abnormalities correlated with clinical manifestations of neurobrucellosis . METHODS: We reviewed 23 MR imaging studies (17 of brain, six of spine) and seven CT scans of brain in 23 patients (14 male and nine female patients; age range 17-71 years) with positive Brucella titers in their serum and CSF . RESULTS: Twelve patients had central nervous system (CNS) involvement, four had peripheral nervous system (PNS) involvement, two had combined PNS and CNS involvement, and five had isolated hearing loss . Imaging findings were variable: five of seven brain CT studies were normal, and 10 of 23 MR studies were normal (eight brain, one thoracic, one lumbar) . One brain CT study showed subthalamic hemorrhage, mild perivascular enhancement, left caudate lacunae, and diffuse white matter changes . One other brain CT study showed enhancement of the tentorium in addition to white matter changes . Abnormal MR findings were basal meningeal enhancement (n = 3), lumbar nerve root enhancement (n = 3), granuloma of the suprasellar region (n = 1), diffuse white matter changes (n = 7), and spinal cord atrophy (n = 1) . All patients improved after treatment with three antimicrobial drugs for 3-12 months . Seven patients had follow-up imaging; the enhancement disappeared but the white matter and ischemic changes persisted despite almost complete clinical recovery . CONCLUSION: Clinical-radiologic correlation in neurobrucellosis varies from a normal imaging study despite positive clinical findings, to a variety of imaging abnormalities that reflect either an inflammatory process, an immune-mediated process, or a vascular insult. Int J Antimicrob Agents, 2004 Mar, 23 Suppl 1, S75 - 8 Prevention of catheter-related infections: the potential of a new nano-silver impregnated catheter; Samuel U et al.; Contaminated or infected catheters are a major source of nosocomial infections responsible for >40% of all episodes of nosocomial sepsis in acute-care hospitals . Antibiotics as well as surface modifications with, for example, hydrogels proved to be of little value in preventing the contamination of indwelling catheters . The even distribution of 10(12-13) activated silver nanoparticles per gram in various polymers, e.g . polyurethane and silicone, results in an excellent antimicrobial activity against a broad spectrum of organisms in vitro . Substantial reduction of incrustation of these catheters was also observed . These preliminary experimental data warrant clinical studies. Int J Antimicrob Agents, 2004 Mar, 23 Suppl 1, S17 - 23 Controversies in antibiotic prophylaxis in urology; Grabe M; Antibiotic prophylaxis in urologic surgery remains controversial . However, progress has been made and some of the controversies have been answered . Firstly, it is important to underline that urologic diagnostic and therapeutic procedures can induce surgical site infections (SSIs), bacteriuria, pyelonephritis and septicaemia in a substantial number of patients, too great to be neglected . Secondly, as patients are different and have various risk factors, a careful assessment of the patient and its individual risk is crucial . Thirdly, the same procedure may be totally different from one individual to another and they can rarely be grouped as standard procedures . A floating level of invasiveness is followed by a variation of the risk of infection . Fourthly, the pathogens and their susceptibility pattern vary extensively in Europe so that no clear-cut recommendations as for the choice of antibiotics can be given . Basic principles of antibiotic prophylaxis in terms of timing, mode of administration and length of regiment apply for urologic interventions . Thus, clean operations will usually not require antimicrobial prophylaxis except for those including the implant of a prosthetic device, while clean-contaminated will benefit from preventive antimicrobials . It is the task of the urologists to carefully assess each individual patient and procedure to opt for an optimal prophylaxis. Chem Phys Lipids, 2004 Mar, 128(1-2), 135 - 48 The isoprostanoid pathway in plants; Thoma I et al.; Higher plants are generally unable to synthesize arachidonic acid, and thus, do neither form prostaglandins nor C20-isoprostanes . Instead, plants utilize linolenic acid for the synthesis of prostaglandin-like compounds of the jasmonate type via the lipoxygenase/allene oxide synthase pathway and C18-isoprostanoids, termed phytoprostanes, via a nonenzymatic, free radical catalyzed pathway analogous to the isoprostane pathway in animals . Both pathways are constitutively present in many if not all plants . Formation of jasmonates can be triggered by specific stimuli interacting with membrane receptors while phytoprostane synthesis can be induced by ROS and heavy metals . Jasmonates are established plant signal compounds that induce defense responses including accumulation of antimicrobial secondary metabolites (phytoalexins) . Preliminary data indicates that phytoprostanes also induce phytoalexins in a variety of plant species suggesting a possible function of phytoprostanes as mediators of defense reactions in response to oxidative stress in plants. Trends Biotechnol, 2004 Mar, 22(3), 142 - 6 Potential applications of microbial surfactants in biomedical sciences; Singh P et al.; The main commercial use of biosurfactants is in pollution remediation because of their ability to stabilize emulsions . This enhances the solubility and availability of hydrophobic pollutants, thus increasing their potential for biodegradation . One useful property of many biosurfactants that has not been reviewed extensively is their antimicrobial activity . Several biosurfactants have strong antibacterial, antifungal and antiviral activity . Other medically relevant uses of biosurfactants include their role as anti-adhesive agents to pathogens, making them useful for treating many diseases and as therapeutic and probiotic agents . Here, we discuss some of the new and exciting applications and related developments of various microbial surfactants in the field of biomedical sciences. Biochemistry, 2004 Mar 30, 43(12), 3590 - 9 Energetics of pore formation induced by membrane active peptides; Lee MT et al.; Antimicrobial peptides are known to form pores in cell membranes . We study this process in model bilayers of various lipid compositions . We use two of the best-studied peptides, alamethicin and melittin, to represent peptides making two types of pores, that is, barrel-stave pores and toroidal pores . In both cases, the key control variable is the concentration of the bound peptides in the lipid bilayers (expressed in the peptide-lipid molar ratio, P/L) . The method of oriented circular dichroism (OCD) was used to monitor the peptide orientation in bilayers as a function of P/L . The same samples were scanned by X-ray diffraction to measure the bilayer thickness . In all cases, the bilayer thickness decreases linearly with P/L and then levels off after P/L exceeds a lipid-dependent critical value, (P/L)* . OCD spectra showed that the helical peptides are oriented parallel to the bilayers as long as P/L < (P/L)*, but as P/L increases over (P/L)*, an increasing fraction of peptides changed orientation to become perpendicular to the bilayer . We analyzed the data by assuming an internal membrane tension associated with the membrane thinning . The free energy containing this tension term leads to a relation explaining the P/L-dependence observed in the OCD and X-ray diffraction measurements . We extracted the experimental parameters from this thermodynamic relation . We believe that they are the quantities that characterize the peptide-lipid interactions related to the mechanism of pore formation . We discuss the meaning of these parameters and compare their values for different lipids and for the two different types of pores . These experimental parameters are useful for further molecular analysis and are excellent targets for molecular dynamic simulation studies. Clin Infect Dis, 2004 Apr 1, 38(7), 934 - 8 Epub 2004 Mar 15. Role of infectious diseases consultants in management of antimicrobial use in hospitals; Sunenshine RH et al.; The Infectious Diseases Society of America Emerging Infections Network (EIN) surveyed its members to characterize antimicrobial restriction policies in their hospitals and the involvement of infectious diseases consultants in this process . Of the 502 respondents (73%), 250 (50%) indicated that their hospital pharmacies would not dispense certain antimicrobials without approval of infectious diseases consultants . Moreover, 89% agreed that infectious diseases consultants need to be directly involved in the approval process . At hospitals with control policies, commonly restricted agents included lipid formulations of amphotericin B, carbapenems, fluoroquinolones, piperacillin-tazobactam, and vancomycin . Only 46 EIN members (18%) reported remuneration of infectious diseases consultants for participation in the approval process . Pediatric infectious diseases consultants were more likely to practice in hospitals with restriction policies than were adult infectious diseases consultants (64% vs . 45%; P<.001) . Similarly, teaching hospitals were more likely to have antimicrobial-control policies than were nonteaching facilities (60% vs . 17%; P<.001). Med Oncol, 2004, 21(1), 21 - 30 Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo; Vigushin DM et al.; Gliotoxin is a natural mycotoxin with immunosuppressive and antimicrobial activity . Inhibition of farnesyltransferase (IC50 80 microM) and geranylgeranyltransferase I (IC50 17 microM) stimulated interest in the potential antitumor activity of this epidithiodioxopiperazine . Gliotoxin inhibited proliferation of six breast cancer cell lines in culture with mean +/- SD IC50 289 +/- 328 microM (range 38-985 microM); intracellular farnesylation of Lamin B and geranylgeranylation of Rap1A were inhibited in a dose-dependent manner . In randomized controlled studies using the N-methyl-N-nitrosourea rat mammary carcinoma model, gliotoxin had pronounced antitumor activity in vitro and little systemic toxicity when administered to 10 animals at 10 mg/kg by subcutaneous injection weekly for 4 wk compared with 10 controls . Single doses up to 25 mg/kg were well tolerated . The present studies confirm that gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with pronounced antitumor activity and favorable toxicity profile against breast cancer in vitro and in vivo. Endocrinology, 2004 Jul, 145(7), 3165 - 73 Epub 2004 Mar 19. The androgen-regulated epididymal sperm-binding protein, human beta-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial beta-defensin; Yenugu S et al.; Spermatozoa bind a variety of proteins as they pass through the proximal regions of the epididymis, where they acquire forward motility and fertilizing ability . Recent evidence indicates that certain epididymis-specific secretory proteins that bind sperm have antibacterial activity and may function as part of the innate immune system . We reported earlier that ESC42, now designated human beta-defensin 118 (DEFB118), is a sperm-binding protein . In this study, we demonstrate that DEFB118 has potent antibacterial activity that is dose, time, and structure dependent . Incubation of Escherichia coli for 60 min with 10 microg/ml DEFB118 reduced bacterial survival to 20% of the control, and 25 microg/ml reduced survival to 5% of the control . DEFB118 concentrations of 50 and 100 microg/ml further reduced survival to less than 2 and 1%, respectively . A biphasic effect of salt concentration on the antibacterial activity of DEFB118 was observed . Reduction of disulfide bonds and alkylation of cysteines resulted in the complete loss of antibacterial activity . DEFB118 caused rapid permeabilization of both outer and inner membranes of E . coli and striking morphological alterations in the bacterial surfaces visible by scanning electron microscopy consistent with a membrane-disruptive mechanism of bacterial killing . In contrast, eukaryotic cell membranes were not permeabilized by DEFB118, as indicated by the rat erythrocyte hemolytic assay . Studies on DEFB118 inhibition of macromolecular synthesis and membrane permeability in E . coli were consistent with a primary effect at the cell membrane level . DEFB118 may contribute to epididymal innate immunity and protect the sperm against attack by microorganisms in the male and female reproductive tracts. Contraception, 2004 Apr, 69(4), 333 - 8 Contraceptive efficacy of antimicrobial peptide Nisin: in vitro and in vivo studies; Aranha C et al.; Sexually transmitted infections and unplanned pregnancies present a great risk to the reproductive health of women . Therefore, female-controlled vaginal products directed toward disease prevention and contraception are needed urgently . In the present study, efforts were made to evaluate the contraceptive potential of Nisin . The effect of Nisin on sperm motility was assessed under in vitro and in vivo conditions . The results showed that sperm motility was completely inhibited with Nisin . The minimum effective concentration of Nisin required to immobilize sperm (80-100 x 10(6)) in vitro within 20 s was found to be 50 microg in rat, 200 microg in rabbit and 300-400 microg in monkey and human . The effect on sperm motility was observed to be dose- and time-dependent . Intravaginal administration of Nisin (200 microg) before mating during proestrus-estrous transition phase caused complete arrest of sperm motility and blockage of conception . Subacute toxicity studies in rats indicated that, repetitive intravaginal application of Nisin at the dose of 200 microg for 14 consecutive days induced no abnormalities either in the length of estrous cycle or in the morphology of vaginal epithelial cells . No histopathological abnormalities in vaginal tissue or any change in blood and serum biochemical profiles were observed . Furthermore, no adverse effects were observed on subsequent reproductive performance, neonate survival and development of pups . It is suggested that Nisin, with its antibacterial and spermicidal activities, could be developed as a potent vaginal contraceptive for future use in humans. Enferm Infecc Microbiol Clin, 2003 May, 21 Suppl 2, 64 - 71 {The future of antimicrobial susceptibility testing}; Martinez-Martinez L; Antimicrobial susceptibility testing is one of the more clinically relevant activities on the management of infected patients . There is not definitive demonstration that, from a clinical point of view, obtaining MIC is better than determining clinical categories, but several evidences indicate that MIC values are actually useful . Several studies have shown that it is more relevant to demonstrate resistance than to demonstrate susceptibility . Different committees have established breakpoints for defining clinical categories that may differ in some cases . It would be necessary to reach an agreement in defining these breakpoints, as well as in standardizing methods for antibiogram . The introduction of the Etest has been one of the main methodological developments in the last years, but its cost may limit its use . Several automatic methods have been developed with improved level of automation and being able of providing susceptibility testing results on the same day of the inoculation of panels . Some methods based on digital lecture are able to automatically read disk diffusion plates . Although major advances in molecular methods have been obtained, we are still far of its routine use in clinical laboratories; it is possible that microchips may contribute in this direction . Computers have been successfully applied to the development of expert systems for interpretative reading of the antibiogram and for developing surveillance programs for resistant microorganisms . Obtaining rapid susceptibility testing results that are made available to the clinician as soon as possible has great clinical impact in terms of therapeutic success, better antimicrobial use and reduced costs. Enferm Infecc Microbiol Clin, 2003 May, 21 Suppl 2, 37 - 43 {Blood cultures and cerebrospinal fluid}; Pascual A; Despite the important advances in the molecular diagnosis of infectious diseases, blood cultures keeps being a key tool for the diagnosis of sepsis . Currently, the conventional methods are being adapted to shorten the time of emission of final results, particularly those related to identification and susceptibility to antimicrobial agents . The direct information from microbiologists to clinicians improves the choice of antimicrobial therapy and decreases the costs of hospitalization . In infectious meningitis, although the use of conventional methods, Gram stain and culture, is needed, the application of new molecular methods will be particularly useful since the number on pathogens and their resistance or virulence genes to be detected, are more limited. Enferm Infecc Microbiol Clin, 2003 May, 21 Suppl 2, 32 - 6 {The role of the microbiologist in the control of nosocomial infection and antibiotic therapy}; Bouza E; The microbiologist is a key figure in the control of hospital infection and in antimicrobial policy . Some of the contributions to the area of documentation and information can be summarized as follows: information on the development of isolation of sentinel microorganisms and their distribution in services and areas, the development of resistance of the various microorganisms to the most commonly used antimicrobial agents, molecular characterization of the isolated microorganisms causing epidemic outbreaks and the control of environmental microorganisms posing a threat to hospitals.Concerning interventions, microbiologists make a substantial contribution to teaching activity and to the continuing education required to maintain optimal knowledge on infections and microbiology in hospitals . They also recommend therapeutic approaches to the presence of isolated microorganisms and specific situations, collaborate in the design of antimicrobial prophylaxis and illustrate the policy of patient isolation . Microbiologists play a key role in decisions to introduce new drugs in hospitals and in programs to limit their inappropriate use.Finally, microbiologists and microbiology services constitute a central element where all the activities required for the diagnosis, treatment and control of infection performed by the various hospital services converge. Biochem J, 2004 Jun 15, 380(Pt 3), 859 - 65 Effects of the antimicrobial peptide temporin L on cell morphology, membrane permeability and viability of Escherichia coli; Mangoni ML et al.; Antimicrobial peptides are produced by all organisms in response to microbial invasion and are considered as promising candidates for future antibiotics . There is a wealth of evidence that many of them interact and increase the permeability of bacterial membranes as part of their killing mechanism . However, it is not clear whether this is the lethal step . To address this issue, we studied the interaction of the antimicrobial peptide temporin L with Escherichia coli by using fluorescence, confocal and electron microscopy . The peptide previously isolated from skin secretions of the frog Rana temporaria has the sequence FVQWFSKFLGRIL-NH2 . With regard to fluorescence microscopy, we applied, for the first time, a triple-staining method based on the fluorochromes 5-cyano-2,3-ditolyl tetrazolium chloride, 4',6-diamidino-2-phenylindole and FITC . This technique enabled us to identify, in the same sample, both living and total cells, as well as bacteria with altered membrane permeability . These results reveal that temporin L increases the permeability of the bacterial inner membrane in a dose-dependent manner without destroying the cell's integrity . At low peptide concentrations, the inner membrane becomes permeable to small molecules but does not allow the killing of bacteria . However, at high peptide concentrations, larger molecules, but not DNA, leak out, which results in cell death . Very interestingly, in contrast with many antimicrobial peptides, temporin L does not lyse E . coli cells but rather forms ghost-like bacteria, as observed by scanning and transmission electron microscopy . Besides shedding light on the mode of action of temporin L and possibly that of other antimicrobial peptides, the present study demonstrates the advantage of using the triple-fluorescence approach combined with microscopical techniques to explore the mechanism of membrane-active peptides in general. Curr Med Chem, 2004 Mar, 11(6), 765 - 73 Developing inhibitors to selectively target two-component and phosphorelay signal transduction systems of pathogenic microorganisms; Stephenson K et al.; Two-component signal transduction systems and their expanded variants known as phosphorelays are integral elements of the virulence and antimicrobial resistance responses of a wide range of pathogenic bacteria and fungi and also regulate essential functions . As a consequence, two-component systems and phosphorelays are recognized targets for the development of novel antimicrobial agents and a number of chemically synthesized inhibitors from different chemical classes have been identified by compound library screens . However, in the majority of cases these compounds do not appear to be selective for signal transduction pathways and exert their effect by multiple mechanisms of action . The key to designing molecules to selectively disrupt signal transduction may lie with the conserved features of response regulators and the structural analysis of complexes of signaling proteins. Annu Rev Immunol, 2004, 22, 817 - 90 CD1: antigen presentation and T cell function; Brigl M et al.; This review summarizes the major features of CD1 genes and proteins, the patterns of intracellular trafficking of CD1 molecules, and how they sample different intracellular compartments for self- and foreign lipids . We describe how lipid antigens bind to CD1 molecules with their alkyl chains buried in hydrophobic pockets and expose their polar lipid headgroup whose fine structure is recognized by the TCR of CD1-restricted T cells . CD1-restricted T cells carry out effector, helper, and adjuvant-like functions and interact with other cell types including macrophages, dendritic cells, NK cells, T cells, and B cells, thereby contributing to both innate and adaptive immune responses . Insights gained from mice and humans now delineate the extensive range of diseases in which CD1-restricted T cells play important roles and reveal differences in the role of CD1a, CD1b, and CD1c in contrast to CD1d . Invariant TCR alpha chains, self-lipid reactivity, and rapid effector responses empower a subset of CD1d-restricted T cells (NKT cells) to have unique effector functions without counterpart among MHC-restricted T cells . This review describes the function of CD1-restricted T cells in antimicrobial responses, antitumor immunity, and in regulating the balance between tolerance and autoimmunity. Annu Rev Immunol, 2004, 22, 361 - 403 Autoimmune and inflammatory mechanisms in atherosclerosis; Wick G et al.; The present review focuses on the concept that cellular and humoral immunity to the phylogenetically highly conserved antigen heat shock protein 60 (HSP60) is the initiating mechanism in the earliest stages of atherosclerosis . Subjecting arterial endothelial cells to classical atherosclerosis risk factors leads to the expression of HSP60 that then may serve as a target for pre-existent cross-reactive antimicrobial HSP60 immunity or bona fide autoimmune reactions induced by biochemically altered autologous HSP60 . Endothelial cells can also bind microbial or autologous HSP60 via Toll-like receptors, providing another possibility for targetting adaptive or innate immunological effector mechanisms. Annu Rev Immunol, 2004, 22, 181 - 215 Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense; Yang D et al.; Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or cathelicidins . The direct in vitro microbicidal activity of antimicrobial proteins has long been considered an important innate immune defense, although the in vivo relevance has only very recently been established for certain defensins and cathelicidins . Mammalian defensins and cathelicidins have also been shown to have multiple receptor-mediated effects on immune cells . Beta-defensins interact with CCR6; murine beta-defensin-2 in addition activates TLR4 . Cathelicidins act on FPRL1-expressing cells . Furthermore, several defensins have considerable immunoenhancing activity . Thus, it appears that mammalian antimicrobial proteins contribute to both innate and adaptive antimicrobial immunity. J Manag Care Pharm, 2004 Mar-Apr, 10(2), 152 - 8 Improving antimicrobial use: longitudinal assessment of an antimicrobial team including a clinical pharmacist; Arnold FW et al.; BACKGROUND: Inappropriate antimicrobial utilization in hospitalized patients has been associated with adverse effects, emergence of resistant bacteria, and increased health care cost . Participation of clinical pharmacists, working as an integral part of a hospital antimicrobial management team (AMT), has been shown to improve antimicrobial use; however, the long-term impact of such a team on antimicrobial use is unclear . OBJECTIVE: Our primary objective was to evaluate whether the number of recommendations to improve antimicrobial use made by a hospital AMT decreased over time . Our secondary objective was to identify and evaluate the acceptance of AMT recommendations with respect to the clinical service, site of infection, and category of suboptimal use . METHODS: We retrospectively reviewed antimicrobial utilization data collected by the team for the 3-year period from July 1996 to June 1999 at the Veterans Affairs Medical Center in Louisville, Kentucky . The total number of antimicrobial treatment episodes and the number of recommendations were grouped into periods of 6 months each during the 3 years . The type of recommendation, type of infection, and clinical service (medicine versus surgery) were reviewed for the entire 3-year period . RESULTS: The number of antimicrobial treatment episodes for each of the 6-month consecutive periods was 404, 526, 406, 549, 507, and 612 . The proportion of episodes requiring team recommendations was constant over the 5 consecutive periods: 39%, 37%, 36%, 36%, 35%, and 37% . (P = 0.8) . Acceptance rates of AMT recommendations by the internal medicine and general surgery services remained stable over the length of the study, 84% and 69%, respectively . The distribution of patients treated by the site of infection also remained stable over the study period . CONCLUSION: Our results demonstrate that despite the long-term presence of an AMT, the proportion of antimicrobial episodes requiring intervention and the percentage of accepted recommendations remained constant over a 3-year period . Having new resident physicians in teaching hospitals or staff turnover in managed care organizations may necessitate the continued presence of an active AMT. J Chem Inf Comput Sci, 2004 Mar-Apr, 44(2), 515 - 21 Designing antibacterial compounds through a topological substructural approach; Molina E et al.; A novel application of TOPological Substructural MOlecular DEsign (TOPS-MODE) was carried out in antibacterial drugs using computer-aided molecular design . Two series of compounds, one containing antibacterial and the other containing non-antibacterial compounds, were processed by a k-means cluster analysis in order to design training and predicting series . All clusters had a p-level < 0.005 . Afterward, a linear classification function has been derived toward discrimination between antibacterial and non-antibacterial compounds . The model correctly classifies 94% of active and 86% of inactive compounds in the training series . More specifically, the model showed a global good classification of 91%, i.e., 263 cases out of 289 . In predicting series, the model has shown overall predictabilities of 91 and 83% for active and inactive compounds, respectively . Thereby, the model has a global percentage of good classification of 89% . The TOPS-MODE approach, also, similarly compares with respect to one of the most useful models for antimicrobials selection reported to date. J Antibiot (Tokyo), 2004 Jan, 57(1), 52 - 8 Tripropeptins, novel antimicrobial agents produced by Lysobacter sp; Hashizume H et al.; Planar structures of tripropeptins (TPPs) were elucidated by spectroscopic studies including various NMR measurements . Stereochemistry of constituent amino acids of tripropeptin C (TPPC) (3) was identified by marfey's method except hydroxyproline which was determined by studies of NMR and CD spectra . The absolute structure of 3 was determined by analyses of the fragments obtained by Birch reduction and LiBH4 reduction of 3 . The configuration of the fatty acid, isolated from acid hydrolysate of 3, was determined to be (3R)-hydroxy-13-methyltetradecanoic acid from MS, NMR spectra and negative sign of the optical rotation. J Anim Sci, 2004 Mar, 82(3), 845 - 50 Effects of dietary energy and starch concentrations for newly received feedlot calves: II . Acute-phase protein response; Berry BA et al.; Two hundred forty five market-stressed bull and steer calves (205 +/- 14 kg) were received in January and September 2001 to determine the response of acute-phase proteins to dietary energy and starch concentrations and to determine whether acute-phase proteins could be used as a diagnostic or prognostic tool for calves affected by bovine respiratory disease . On arrival, calves were randomly assigned to one of two dietary energy levels (0.85 or 1.07 Mcal of NEg/kg of DM) and one of two dietary starch levels (34 or 48% of dietary ME from starch; n = 5 pens/treatment) . All calves were weighed, and plasma and serum samples were collected from a subset of animals (n = 6 calves/pen; 30 calves/treatment) on d 0, 7, 14, 28, and 42 of the receiving period . This subset of calves (n = 120) was used for all subsequent analyses . Concentrations of fibrinogen (Fb), haptoglobin (Hp), and serum amyloid-A (SaA) were determined . In addition, samples were collected from the subset of calves when they received medical treatment and 7 d following treatment to measure serum concentrations of Hp and SaA . Serum concentrations of Fb, Hp, and SaA did not differ among dietary treatments, but decreased (P < 0.03) as day of the receiving period increased . Fibrinogen (P < 0.001) and the ratio of Fb:total blood protein were greater (P < 0.003) in calves treated multiple times than in calves never treated or treated once for bovine respiratory disease . In addition, on d 0 and 7, Hp concentration increased (antimicrobial treatment x day interaction, P < 0.03) as the number of antimicrobial treatments increased, and was greater on d 14 and 28 in calves treated multiple times than in calves never treated or treated once . Haptoglobin concentration was greater (P < 0.05) in calves on medical treatment days compared with recovery days (7 d after medical treatment) . Although diet seemed to have little effect on acute-phase protein response, these results suggest that haptoglobin may be useful as a diagnostic tool to make management decisions regarding treatment protocols for calves with bovine respiratory disease. J Chromatogr A, 2004 Mar 12, 1029(1-2), 57 - 65 Optimization by experimental design and artificial neural networks of the ion-interaction reversed-phase liquid chromatographic separation of twenty cosmetic preservatives; Marengo E et al.; Particular attention are recently receiving antimicrobial agents added as preservatives in hygiene and cosmetics commercial products, since some of them are suspected to be harmful to the human health . The preservatives used belong to different classes of chemical species and are generally used in their mixtures . Multi-component methods able to simultaneously determinate species with different chemical structure are therefore highly required in quality control analysis . This paper presents an ion interaction RP-HPLC method for the simultaneous separation of the 20 typical antimicrobial agents most used in cosmetics and hygiene products, that are: benzoic acid, salicylic acid, 4-hydroxybenzoic acid, methyl-, ethyl-, propyl-, butyl-, benzyl-benzoate, methyl-, ethyl-, propyl-, butyl-, benzyl-paraben, o-phenyl-phenol, 4-chloro-m-cresol, triclocarban, dehydroacetic acid, bronopol, sodium pyrithione and chlorhexidine . For the development of the method and the optimization of the chromatographic conditions, an experimental design was planned and models were built by the use of artificial neural network to correlate the retention time of each analyte to the variables and their interactions . The neuronal models developed showed good predictive ability and were used, by a grid search algorithm, to optimize the chromatographic conditions for the separation of the mixture. Kekkaku, 2004 Feb, 79(2), 39 - 46 {Relations between clinical subtypes of Mycobacterium avium pulmonary disease and polyclonal infections detected by IS1245 based restriction fragment length polymorphism analysis}; Kuwabara K et al.; INTRODUCTION: The epidemiology of Mycobacterium avium-intracellulare (MAC) infections has not been completely defined . Recently some reports presented polyclonal MAC infections . The purpose of this study was to reveal the clonal diversity of Mycobacterium avium isolates and the relation between clinical subtype of lung disease and polyclonal infection . METHODS: We categorized pulmonary Mycobacterium avium infection to three clinical subtypes, tuberculosis like type, bronchiectasis with preexisting tuberculosis type and nodular bronchiectasis type . Mycobacterium avium isolates of 11 patients were studied for their heterogeneity using IS1245 based RFLP analysis . The insertion sequence IS1245 is repetitive element identified only in Mycobacterium avium . Standard method of IS1245 based RFLP analysis has been proposed as a suitable technique for typing of Mycobacterium avium isolates for epidemiological and taxonomic studies . At least three distinct colonies were subcultured to single clone . The subclones of the isolates were analyzed by IS1245 based RFLP technique and some subclones were also examined by antimicrobial susceptibility test . RESULTS: Two of three patients of tuberculosis like type were considered to be monoclonal infection because only a single genotype was identified . And only one of four patients of bronchiectasis with preexisting tuberculosis type was considered to be polyclonal infection despite of long-term observation . Although isolates were collected in two or more occasions in clinical course over one year period, only a single genotype was observed in two patients . In contrast, three of four patients of nodular bronchiectasis type had multiple genotypes . Isolates recovered from patients with monoclonal infection pattern following long-term treatment with clarithromycin monotherapy became resistant to clarithromycin . In contrast, three strains derived from one nodular bronchiectasis patient were susceptible to clarithromycin despite of long-term chemotherapy including clarithromycin . The susceptibility patterns of the other drugs were also apparently different . Strain conversion due to repeated polyclonal infection was considered . These results of the antimicrobial susceptibility test supported clonal diversity of the Mycobacterium avium infection . DISCUSSION: IS1245 based RFLP analysis possesses a discriminatory power between the isolates on clonal level . This study demonstrates that polyclonal infections are common in nodular bronchiectasis type and monoclonal infections are common in tuberculosis like type and bronchiectasis with preexisting tuberculosis type . And not only simultaneous polyclonal infection but also repeated polyclonal infection were observed in a nodular bronchiectasis type patient . Drug susceptibility test showed long-term chemotherapy including clarithromycin could change the susceptibility of clarithromycin to resistant in patients with monoclonal infection . In contrast patients with repeated polyclonal infection pattern would avoid drug resistance because of strain conversion . This multiple susceptibility patterns identified in this study would not have been detected by the standard susceptibility test without subculture . And we also need the treatment strategy considering the polyclonal infection . CONCLUSIONS: Polyclonal infections are considered to be common in pulmonary Mycobacterium avium infection, especially nodular bronchiectasis type . Clonal diversity of Mycobacterium avium infection is an important factor to perform chemotherapy and drug susceptibility test. Fitoterapia, 2004 Mar, 75(2), 201 - 3 Antimicrobial activity of four Artemisia species of Iran; Ramezani M et al.; The antimicrobial activities of methanol extracts of four species of Artemisia species of Iran are reported. Ann Fr Anesth Reanim, 2004 Mar, 23(2), 116 - 23 {Antimicrobial prophylaxis in surgical procedures: assessment of the guidelines application and validation of antibiotic prophylaxis kits}; Gindre S et al.; INTRODUCTION: Surgical wounds infections represent a major cause of morbidity and are at the origin of an increase in the postoperative mortality rate . Those infections represent in France one-fourth of the nosocomial infections . Combine with the elementary hygiene rules and the surgical "good practices", antimicrobial prophylaxis with antibiotics is an essential tool for the reduction of the surgical wound infections rate . In the French hospitals, antimicrobial prophylaxis represents one-third of the antibiotic prescriptions . The rules for the application of surgical prophylaxis are based on current guidelines for antibiotic prophylaxis, however, guidelines are not totally respected . MATERIALS AND METHODS: Study 1: assessment of the guidelines application (practical audit) of the antibiotic antimicrobial prophylaxis in surgery, and of their impact on the established prescriptions: three audits were realized with four years interval (1994, 1998 and 2002), in order to estimate the evolution in the application of the current guidelines, which indirectly estimate the evolution of the guidelines impact . Study 2: assessment of the use of an antibiotic kit through a prospective comparative study of two groups: exposed patients vs non-exposed patients . Nominatives kits contained the recommended antibiotics with recommended posology and the instructions for each surgical procedure . RESULTS: Study 1: this study showed a significant increase in the antibiotics prescription volume since 1994 (+23%) . After a temporary increase from 1994 to 1998, the conformity of the effective prescriptions with the current guidelines for the indication to realize or not to realize an antibiotic surgical prophylaxis decreases of 7% between 1998 and 2002 . Nevertheless, we noticed an overall improvement in the guidelines application for the modalities of the antimicrobial prophylaxis when it was prescribed in a valid indication . Persistent weak points were in 2002 the antibiotic molecule choice (error rate of 25%), the duration of prescription (rate of abnormal prolonged antibiotic prophylaxis of 19%), and the timing of administration (error rate of 31%) . Study 2: antibiotic kits have permitted to increase the accordance of the antimicrobial prophylaxis prescriptions with the guidelines . Antibiotic prophylaxis was in total agreement with guidelines for 82% of exposed patients vs 41 for non-exposed patients . Choice of the antibiotic molecule, timing of administration and duration of prescription were the parameters particularly well rectified by this new antibiotic prophylaxis technical . CONCLUSION: In this study, guidelines diffusion seems to be an essential but also an insufficient point for the improvement of the quality prescriptions in surgical antimicrobial prophylaxis . The "day by day" nominative antibiotic prophylaxis deliverance in the shape of a << ready to use >> antibiotic kit went with an increase in the respect of the recommendations, by correcting in a significant way the persistent weak points identified during the first part of our study . The antibiotic prescriptions control is an imperative goal in individual health (the patient himself), but also in public health (the community) . This radical change in habits is listed in a policy of antimicrobial agent prescription improvement (best efficacy with less cost). Emerg Infect Dis, 2004 Feb, 10(2), 339 - 41 Index patient and SARS outbreak in Hong Kong; Wong RS et al.; During the global outbreak of severe acute respiratory syndrome (SARS) in 2003, treatment was empiric . We report the case history of the index patient in a hospital outbreak of SARS in Hong Kong . The patient recovered after conventional antimicrobial therapy . Further studies are needed to address treatment of SARS, which has high attack and death rates. J Vet Med B Infect Dis Vet Public Health, 2004 Mar, 51(2), 77 - 81 Occurrence of Escherichia coli O157 in raw material and food in Czech Republic; Lukasova J et al.; The study was carried out to investigate the incidence of Escherichia coli O157 in raw materials, foodstuffs and the agricultural environment . Of a total of 987 samples examined, 22 strains (2.2%) were identified as E . coli O157 and 10 of them as E . coli O157:H7 . Cefixime-Tellurite MacConkey sorbitol agar (CT-SMAC) agar and Biosynth culture medium (BCM) E . coli O157:7 medium were used for the isolation . The virulence factors (stx1, stx2, eae, and ehxA genes) were identified by polymerase chain reaction (PCR) . Most strains were isolated from the mechanically deboned poultry meat (nine), minced meat (six) and raw milk (four) . One strain was isolated from beef carcass and two strains from waste water . No strains were were found in mass for sausages, refreshment salads, swabs of pork and poultry carcasses and faeces of cattle and pigs . Ten strains from the 22 identified proved to be positive for all factors of virulence . They were isolated from minced meat (four), raw milk (four), waste water (one) and swab from beef carcass (one) . Sensitivity to the antimicrobial drugs ampicillin (AMS), ampicillin-sublactam (SAM), tetracycline (TET), ofloxacine (OFL), cefuroxime (CRX), chloramphenicol (CPM), gentamicine (GEN), colistin (COL), cephalozine (CLZ), cefoxitin (CXT), aztreonam (AZT), and sulphamethoxazole + trimethoprim (COT) was tested using the standard dilution technique and disc diffusion test . Minimum inhibitory concentrations (MIC) characteristics (MIC(50), MIC(90), MIC range) and inhibitory zone diameter were determined for each strain . As determined by MICs, the resistance to tested antibiotics in E . coli O157 isolates was found to AMS (90.9%), CLZ (81.8%), CRX (63.6%), CXT (72.7%), CPM (72.7%), TET (81.8%), SAM (59.1%), COT (9.1%), COL (63.61%), AZT (9%) and GEN (4.5%) . The similar results were obtained using the disc diffusion method . The differences were found relating to SAM, CXT, CMO and TET . Resistance against one or more antibiotics was found in 95.4% of E . coli O157 . Only one strain was susceptible to all tested antibiotics . Most of the strains were resistant to ampicillin and cephalozine . Eight different resistance phenotypes were demonstrated in E . coli O157. Vet Dermatol, 2004 Apr, 15(2), 127 - 36 Ear cleaning: the UK and US perspective; Nuttall T et al.; Ear cleaning helps maintain the normal otic environment and is important in the treatment of otitis . Over cleaning, however, may trigger otitis through maceration of the epidermal lining . Simple manual cleaning is useful for routine cleansing but doesn't remove tightly adherent debris . Bulb syringes are more vigorous but may damage the ear in inexperienced hands . Devices using mains water pressure or dental machines are also available . Thorough cleaning of the ear canals and middle ear cavity can only be achieved by retrograde flushing using specially adapted catheters, feeding tubes or video otoscopes under anaesthesia . Myringotomy, inspection and cleaning of the middle should be performed if the tympanic membrane appears abnormal . There are a wide variety of cleaning fluids available . Ceruminolytics soften and dissolve cerumen to facilitate cleaning . Surfactants emulsify debris, breaking it up and keeping it in solution . Astringents dry the ear canal surface, preventing maceration . Maintaining a low pH and incorporating antimicrobial agents can inhibit microbial proliferation and glucocorticoids can be used to reduce inflammation . Adverse effects and contraindications following ear cleaning can include maceration, contact reactions, otitis media, ear canal avulsion, vestibular syndrome, Horner's syndrome, facial nerve paralysis and deafness . Care should be exercised in selecting cleaning fluids if the tympanic membranes are ruptured. J Agric Food Chem, 2004 Mar 24, 52(6), 1452 - 7 Beta-thujaplicin: new quantitative CZE method and adsorption to goethite; Dyrskov L et al.; Beta-thujaplicin (beta-TH) is a toxic tropolone derivative present in the heartwood of western red cedar (Thuja plicata) and is used as a preservative and antimicrobial additive in a number of commercial goods . beta-TH released from western red cedar timber used outdoor and from other products containing beta-TH may transfer to soil and leach to groundwater and surface waters . The objective of this study was to quantify the adsorption of beta-TH to goethite as a typical model for geosorbents . Adsorption was studied using pH-adjusted goethite suspensions with solid:solution ratios of 1:500, 0.01 M NaNO(3) electrolyte, and 20 degrees C . beta-TH was determined using a new capillary zone electrophoresis (CZE) method providing a detection limit of 0.21 microM . Near-sorption equilibrium was attained within 48 h . beta-TH showed maximum adsorption at low pH (3.8) and a 70% drop in adsorption from pH 6.2 to 8.8 . The Langmuir type adsorption isotherm at pH 5.5 approached a maximum adsorption of 220 micromol/g (= 6.2 micromol/m(2)), which is more than twice the amount of phosphate adsorbed under similar conditions . The affinity of beta-TH for goethite is low as compared with organic ligands such as citrate, oxalate, and 2,4-dihydroxybenzoate . The adsorption data and FTIR analyses indicate that beta-TH is most likely adsorbed as monodentate mononuclear surface complexes at the surface of goethite . Hydrophobic adsorption is thought to contribute to the adsorption, in particular at low pH . The strong adsorption of beta-TH to goethite suggests low mobility in most soil environments, the risk of contamination increasing in soils with high pH (calcareous material), low contents of iron and aluminum oxides, phyllosilicates, and organic matter. Surv Ophthalmol, 2004 Mar, 49 Suppl 2, S73 - 8 Fluoroquinolones: mechanism of action, classification, and development of resistance; Blondeau JM; The fluoroquinolones represent an evolving class of broad-spectrum antimicrobial agents used in the prevention and treatment of a variety of ocular infections; however, resistance to currently available agents in the class has been emerging among ocular pathogens . This article reviews the mechanism of action of existing and new fluoroquinolones and discusses the structure-activity relationship of the fluoroquinolones as it relates to the classification of these compounds . This article also highlights the mechanism of resistance among common ocular pathogens and discusses the potential need for newer fluoroquinolones in ophthalmology. Ann Dermatol Venereol, 2004 Feb, 131(2), 195 - 7 {Dapsone treatment of folliculitis decalvans}; Paquet P et al.; BACKGROUND: Folliculitis decalvans consists of recurrent patchy painful folliculitis of the scalp causing scarring alopecia . The physiopathology of this condition is still unclear, but is likely a manifestation of chronic neutrophilic bacterial folliculitis . Numerous topical and systemic treatments (corticosteroids, antistaphylococcal antibiotics) have been used with variable results . Based on the dapsone antimicrobial activity and its anti-inflammatory action especially directed to the neutrophil metabolism, we treated two patients with severe folliculitis decalvans with this drug . CASE REPORTS: The patients were treated with dapsone at a daily dose of 75 and 100 mg, respectively for 4 to 6 months . After 1 and 2 months, pustular folliculitis progressively cleared, leaving a residual non inflammatory cicatricial alopecia . When maintaining a dapsone dosage at 25 mg/day no relapse occurred during 3 years and 1 year, respectively . No important adverse effect to dapsone was evidenced . After dapsone withdrawal, a moderate relapse of the disease with pruritus and folliculitis occurred after a few weeks in both cases . The disease relapse rapidly cleared after dapsone reintroduction at a daily dose of 25 mg . COMMENTS: Dapsone at moderate dosage was well tolerated and rapidly effective in treating the two cases of folliculitis decalvans . A long term and low dose (25 mg daily) maintenance treatment avoided disease relapses. J Periodontol, 2004 Jan, 75(1), 106 - 15 The effect of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid matrix metalloproteinase-8 levels in chronic periodontitis; Emingil G et al.; BACKGROUND: Low-dose doxycycline (LDD) is recognized to have non-antimicrobial properties that can therapeutically modulate the host response . The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of LDD in combination with non-surgical periodontal therapy, compared to non-surgical periodontal therapy alone, on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels and clinical parameters over a 12-month period in patients with chronic periodontitis . METHODS: GCF samples were collected, and clinical parameters including probing depth (PD), clinical attachment level, gingival index (GI), and plaque index were recorded . Thirty chronic periodontitis patients were randomized either to a low-dose doxycycline (LDD) or placebo group . The LDD group received low-dose doxycycline (20 mg) b.i.d . for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d . for 3 months plus SRP . The patients were evaluated every 3 months during the 12-month study period . At each visit, all clinical measurements and GCF sampling were repeated . GCF MMP-8 levels were determined by a time-resolved immunofluorescence assay . Intragroup comparisons were tested by the Friedman test followed by Wilcoxon signed-rank test to analyze significance of changes over time . The Mann-Whitney test was used to determine differences between the LDD and placebo groups . RESULTS: Significant improvements were observed in all clinical parameters in both groups over the 12-month period (P < 0.0125) . The LDD group showed a significantly greater reduction in mean PD scores at 9 and 12 months and in mean GI scores at all time points than the placebo group (P < 0.05) . From baseline to 12 months, GCF MMP-8 levels were significantly reduced in both groups (P < 0.0125) . The GCF MMP-8 level in the LDD group was significantly lower than that of the placebo group at 6 months (P < 0.05) . CONCLUSIONS: The present results indicate that low-dose doxycycline therapy in combination with scaling and root planing can reduce GCF MMP-8 levels and improve clinical periodontal parameters in patients with chronic periodontitis . These results provide additional information about the usefulness of low-dose doxycycline therapy as an adjunct to non-surgical periodontal therapy in the long-term management of periodontal disease . The effectiveness and course of low-dose doxycycline therapy can be monitored conveniently by assessing GCF MMP-8 levels. Zh Mikrobiol Epidemiol Immunobiol, 2004 Jan-Feb, (1), 79 - 84 {Potentialities of calcium dependent lectin receptors of antigen presenting cells for the immunotherapeutic preparation development}; Del'vig AA et al.; Publications on C-lectin receptors, multifunctional surface molecules of antigen presenting cells are updated . The study of C-lectin receptors is stipulated by their role in antimicrobial protection . The importance of C-lectin receptors of dendrite cells in the system of the recognition of microbial carbohydrate as well as their properties of the targeted supply of tumor cell and other antigens to dendrite cells with the purpose of the formation of immunity against faintly immunogenic antigens is considered . Suggestion is made on the potential of their use as experimental preparations for immunotherapy. Eur J Clin Microbiol Infect Dis, 2004 Apr, 23(4), 243 - 55 Epub 2004 Mar 13. Pharmacokinetic and pharmacodynamic issues in the treatment of mycobacterial infections; Nuermberger E et al.; The therapy of mycobacterial infections is challenging for a number of reasons . Because mycobacteria are not susceptible to many classes of antibacterial agents, treatment typically requires the use of antimicrobial drugs that are not commonly used and may have small therapeutic windows . For many species, procedures for drug susceptibility testing and optimal treatment regimens have yet to be defined . Finally, because mycobacteria are generally slow to succumb to antimicrobial agents, therapy must be given with multiple drugs for prolonged periods of time, making it necessary to monitor for drug toxicity, drug interactions, and patient nonadherence . Better understanding of the pharmacokinetics and pharmacodynamics of antimycobacterial agents should improve the therapy of mycobacterial infections . Using current treatment strategies for tuberculosis and Mycobacterium avium complex infections as examples, this review highlights basic pharmacokinetic and pharmacodynamic principles and the rationale for combination chemotherapy that should also be applicable to other mycobacterial infections. Asia Pac J Clin Nutr . 2003;12 Suppl:S66. Spasmolysis of combined bee glue and Shaoyao-Gancao-tang on isolated rabbit jejunum; Wang NZ et al.; Background - Propolis (bee glue) is a valuable byproduct of apiculture, which is found in honeybee hives . It has been suggested that propolis-ethanol-extract has antitumour, antimicrobial, antifungal, antiviral, antihepatotoxic, antioxidative, and anti-inflammatory activities . Shaoyao-Gancao-tang, a prescription of Chinese Medicine, consists of water extract of liquorice (Radix Glycyrrhizac) and peony (Paeonialaciflora) roots . Objective - To investigate the effect of combined propolis-ethanol-extract and Shaoyao-Gancao-tang (PSG) on contraction of isolated rabbit jejunum in vitro . Design - PGS was prepared from the ethanol extract of propolis and water extract of 1:1 liquorice and peony roots . One end of the jejunum tube (3-4cm) was fastened to the ventilating pipe of a thermostatic bath, the other end to the tensioning exchanger, which was connected to a Recorder . Outcomes - With the same concentration (0.02%), PSG showed a 31% reduction on the maximum relaxation time compared with propolis-ethanol-extracts or Shaoyao-Gancao-tang (P<0.01, n= 10) . This result indicates that there was a synergistic effect between propolis-ethanol-extracts and Shaoyao-Gancao-tang on the myenteric relaxation of jejunum in vitro . Conclusions - The action of PSG on jejunum smooth muscles is most likely through M-receptors, since acetylcholine induced jejunum contractions were significantly decreased by PSG, and there was a remarkable synergistic effect between atropine and PSG (P<0.001, n= 8) . In conclusions, the PGS showed an antispasmodic activity, and inhibits peristalsis of jejunum smooth muscles via inhibiting M-receptors. Clin Mol Allergy . 2004 Mar 16;2(1):4. Low-dose, long-term macrolide therapy in asthma: An overview; Hatipoglu U et al.; Macrolides, a class of antimicrobials isolated from Streptomycetes more than 50 years ago, are used extensively to treat sinopulmonary infections in humans . In addition, a growing body of experimental and clinical evidence indicates that long-term (years), low (sub-antimicrobial)-dose 14- and 15-membered ring macrolide antibiotics, such as erythromycin, clarithromycin, roxithromycin and azithromycin, express immunomodulatory and tissue reparative effects that are distinct from their anti-infective properties . These salutary effects are operative in various lung disorders, including diffuse panbronchiolitis, cystic fibrosis, persistent chronic rhinosinusitis, nasal polyposis, bronchiectasis, asthma and cryptogenic organizing pneumonia.The purpose of this overview is to outline the immunomodulatory effects of macrolide antibiotics in patients with asthma. Infect Dis Obstet Gynecol, 2003, 11(3), 161 - 5 Bacterial colony counts during vaginal surgery; Culligan P et al.; OBJECTIVE: To describe the bacterial types and colony counts present before and during vaginal surgery . METHODS: A descriptive study was undertaken of patients undergoing vaginal hysterectomy with or without reconstructive pelvic surgery . Aerobic and anaerobic bacterial cultures were obtained immediately before and throughout the surgical cases at preselected time intervals . Standard antimicrobial prophylaxis was administered in all cases . Mean total colony counts and mean anaerobic colony counts were determined by adding all colonies regardless of bacteria type . 'Contamination' was defined as > or = 5000 colony-forming units/ml . RESULTS: A total of 31 patients aged 26 to 82 years (mean age +/- SD, 51 +/- 15) were included . The highest total and anaerobic colony counts were found at the first intraoperative time interval . On the first set of cultures (30 minutes after the surgical scrub), 52% (16/31) of the surgical fields were contaminated, and at 90 minutes, 41% (12/29) were contaminated . A negligible number of subsequent cultures were contaminated . CONCLUSIONS: Any future interventions designed to minimize bacterial colony counts should focus on the first 30 to 90 minutes of surgery. Arch Pediatr, 2003 Dec, 10 Suppl 5, 563s - 568s {Pulmonary anti-Aspergillus defences}; Israel-Biet D; The lung, constantly exposed to inhaled infectious particles, uses a very efficient immune system to insure sterility of the airways . It has to be tightly regulated for the tissues to be kept from its potentially deleterious effects . Pulmonary anti-Aspergillus defences are based upon the concurrent action of innate immunity, non specific but rapidly mobilisable, and of adaptative immunity . The former first consists in natural barriers, namely the respiratory epithelium and its antimicrobial peptides (complement, defensins, collectins) . Then come the phagocytic cells (macrophages and neutrophils), but also the dendritic cells, able to stimulate adaptative responses through the presentation of antigens they have phagocytised ans processed . The Toll-like receptors are among the key ones involved in the recognition of fungal components . Chemokines have a crucial role for the recruitment, maturation and activation of neutrophils, while anti-inflammatory cytokines tightly influence T lymphocytes functional differentiation . These latter, cornerstones of the adaptative immunity, differentiate into two mutually exclusive pathways according to the type of cytokines which they produce . The Th1 one is largely protective in the context of Aspergillus, while the Th2 one is deleterious . However, a good cooperation between these 2 pathways is required for an efficient protection . Pulmonary anti-Aspergillus defences are multifactorial . Innate immunity is crucial but a capacity of the host to generate specific responses is also warranted. Vestn Ross Akad Med Nauk, 2004, (1), 23 - 30 {The sporicidal activity of disinfectants based on hydrogen peroxide}; Kanishchev VV et al.; The authors analyzed the experience of disinfection experts related with the designing of new disinfection chemicals and of their composition variations . The key regularities were defined, which are important for the designing of effective disinfectants with preset properties capable of rapidly and safely inactivating a microbe contamination of different objects in the human habitat . A high antimicrobial activity and good outlooks are demonstrated for disinfectants made on the basis of hydrogen peroxide. Phytother Res, 2004 Feb, 18(2), 114 - 7 Phytotoxic and antimicrobial constituents of Bacopa monnieri and Holmskioldia sanguinea; Chaudhuri PK et al.; The phytochemicals betulinic acid (1), wogonin (2) and oroxindin (3) isolated from the aerial parts of Bacopa monnieri and Holmskioldia sanguinea showed significant antifungal activity against the two fungi Alternaria alternata and Fusarium fusiformis . Inhibition of root growth germination of wheat seeds was observed for all three compounds which showed 100% inhibition at 10 micro g/mL . Compounds (1) and (2) showed potent inhibition of Alternaria alternata compared with oroxindin at a concentration of 4 micro g/mL, whereas compound (2) was an effective inhibitor of both fungi . The structures of the compounds were established by spectral and chemical studies . Am J Physiol Lung Cell Mol Physiol, 2004 Oct, 287(4), L706 - 14 Epub 2004 Mar 12. Myeloperoxidase deficiency enhances inflammation after allogeneic marrow transplantation; Milla C et al.; Myeloperoxidase (MPO)-derived oxidants participate in the respiratory antimicrobial defense system but are also implicated in oxidant-mediated acute lung injury . We hypothesized that MPO contributes to lung injury commonly observed after bone marrow transplantation (BMT) . MPO-sufficient (MPO+/+) and -deficient (MPO-/-) mice were given cyclophosphamide and lethally irradiated followed by infusion of inflammation-inducing donor spleen T cells at time of BMT . Despite suppressed generation of nitrative stress, MPO-/- recipient mice unexpectedly exhibited accelerated weight loss and increased markers of lung dysfunction compared with MPO+/+ mice . The increased lung injury during MPO deficiency was a result of donor T cell-dependent inflammatory responses because bronchoalveolar lavage fluids (BALF) from MPO-/- mice contained increased numbers of inflammatory cells and higher levels of the proinflammatory cytokine TNF-alpha and the monocyte chemoattractant protein-1 compared with wild-type mice . Enhanced inflammation in MPO-/- mice was associated with suppressed apoptosis of BALF inflammatory cells . The inflammatory process in MPO-/- recipients was also associated with enhanced necrosis of freshly isolated alveolar type II cells, critical for preventing capillary leak . We conclude that suppressed MPO-derived oxidative/nitrative stress is associated with enhanced lung inflammation and persistent alveolar epithelial injury. Biochem Biophys Res Commun, 2004 Apr 2, 316(2), 407 - 10 Mitosis increases levels of secretory leukocyte protease inhibitor in keratinocytes; Lai JY et al.; Chronic wounds are a major health care burden . Multiple factors produced by healing wounds play important roles in efficient and orderly wound healing . Secretory leukocyte protease inhibitor (SLPI) is constitutively expressed in epithelial cells, and its expression is increased by inflammation . SLPI has antimicrobial activities and improves wound healing . We hypothesized that SLPI expression correlates with keratinocyte growth rate and is increased by epidermal growth factor (EGF) . Keratinocytes were isolated from neonatal foreskin . Subconfluent and confluent culture conditions were used . SLPI-specific primers were designed for use in quantitative-competitive reverse-transcription polymerase chain reaction assays to detect and quantify SLPI mRNA expression levels . SLPI levels were increased 2-fold in subconfluent cultures and 1.6-fold in confluent cultures to which EGF had been added . Confluent cultures also demonstrated 7-fold (growth factor depleted) and 6-fold (EGF) increase in SLPI RNA copy number, compared to subconfluent cultures . The results indicate that EGF increases SLPI expression. Microvasc Res, 2004 Mar, 67(2), 168 - 81 Functional modulation of smooth muscle cells by the inflammatory mediator CAP37; Gonzalez ML et al.; CAP37, a neutrophil-derived protein, originally identified for its antimicrobial activity is now known to have strong immunoregulatory effects on host cells . Recently, we described its expression and localization within the vascular endothelium associated with atherosclerotic plaques . Since CAP37 is a potent activator of endothelial cells and monocytes, two of the key cellular components of the atherosclerotic plaque, this study was undertaken to determine whether CAP37 had functional effects on smooth muscle cells another important cellular participant in atherosclerosis . Sections from atherosclerotic lesions were stained for the presence of CAP37 and smooth muscle cell alpha actin . The effect of CAP37 on aorta smooth muscle cell migration and proliferation was investigated and the upregulation of adhesion molecules was determined . Immunocytochemistry indicated that CAP37 was present in a subset of smooth muscle cells within atherosclerotic lesions, but was absent in normal vessels . Flow cytometry using double labeling for the proliferation marker Ki-67 and CAP37 demonstrates that CAP37 is mainly expressed in proliferating smooth muscle cells . We show that CAP37 supports migration and proliferation of smooth muscle cells in vitro . Furthermore, CAP37-treated smooth muscle cells expressed higher levels of the cell adhesion molecule ICAM-1 when compared with untreated cells . We suggest that due to its localization to atherosclerotic plaques and its ability to modulate smooth muscle cells, CAP37 may play a role in the progression of this disease. Peptides, 2003 Nov, 24(11), 1771 - 7 Functional characterisation of the 1-18 fragment of esculentin-1b, an antimicrobial peptide from Rana esculenta; Mangoni ML et al.; Esculentin-1 is a 46-amino acid residue peptide isolated from skin secretions of Rana esculenta, displaying the most potent antimicrobial activity among the bioactive molecules found in the secretion, with negligible effects on eukaryotic cell membranes . From skin secretions, the 19-46 fragment of esculentin-1, devoid of antibacterial activity, was also isolated . We studied in detail the activity of the N-terminal fragment (1-18) of esculentin-1 using a synthetic amidated analogue . The results show that this fragment is highly active against most bacterial and fungal species, although at a lower extent than the full-length peptide, being four-fold more potent against Phytophthora nicotianae . It has a reduced activity against human erythrocytes with respect to the full-length peptide . The killing curves in liquid medium are similar for the two molecules and the shorter peptide is able to increase the bacterial outer and inner membrane permeability . Overall these data indicate that the antimicrobial properties of esculentin-1 are exerted by its N-terminal 1-18 region and that the positively charged residue distribution as well as peptide length represent important determinants for cell selectivity. Peptides, 2003 Nov, 24(11), 1763 - 70 Antimicrobial polypeptides of the human colonic epithelium; Howell SJ et al.; The lumen of the human colon is heavily colonized with microbes, but infections across its epithelial surface are infrequent . To address the hypothesis that antimicrobial polypeptides contribute to the barrier function of colonic epithelial cells, we examined cellular extracts from non-inflamed colonic mucosa using an antimicrobial assay . This approach yielded five polypeptides: three antimicrobials were previously identified as ribosomal polypeptides (L30, S19 and ubiquicidin), and two were members of the histone family (H1.5 and H2B) . All exhibited bactericidal activity against Escherichia coli, and with the exception of S19, had been isolated by others based on their potent antimicrobial activity in other cells and tissues . These polypeptides normally reside inside cells and are proposed to contribute to the formation of the functional antimicrobial barrier of the colonic epithelium. Peptides, 2003 Nov, 24(11), 1747 - 52 Antiendotoxin activity of protegrin analog IB-367 alone or in combination with piperacillin in different animal models of septic shock; Giacometti A et al.; The therapeutic efficacy of protegrin peptide IB-367 was investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 1mg Escherichia coli 0111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 X 10(10) CFU of E . coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and puncture . All animals were randomized to receive parenterally isotonic sodium chloride solution, 1mg/kg of IB-367, 60mg/kg piperacillin and 1mg/kg of IB-367 plus 60mg/kg piperacillin . The peptide demonstrated lower level of antimicrobial activity than piperacillin, nevertheless it exhibited the dual properties of antimicrobial and antiendotoxin agent . Finally IB-367 and piperacillin association showed to be the most effective therapeutic approach. Peptides, 2003 Nov, 24(11), 1741 - 6 Susceptibility of Treponema pallidum to host-derived antimicrobial peptides; Cox DL et al.; LL-37 displays potent broad-spectrum activity against a number of pathogenic bacteria and is the only cathelicidin thus far identified in humans . In this study, we examined the capacity of human LL-37 and the similar CAP-18-derived peptide from rabbits to exert antimicrobial activity against the causative agent of syphilis, Treponema pallidum . We found that both peptides, as well as a truncated version of human LL-37 that contains its bactericidal domain, could exert rapid, but salt-sensitive antimicrobial activity against T . pallidum . Infectivity of T . pallidum in a rabbit model could effectively be blocked with the synthetic truncated LL-37-derived peptide WS22-N-amide. Peptides, 2003 Nov, 24(11), 1723 - 31 In vitro and in vivo antimicrobial activity of two alpha-helical cathelicidin peptides and of their synthetic analogs; Benincasa M et al.; Two alpha-helical antimicrobial peptides (BMAP-27 and -28) and four synthetic analogs were compared for in vitro and in vivo antimicrobial efficacy . All peptides proved active in vitro at micromolar concentrations against a range of clinical isolates, including antibiotic-resistant strains . BMAP-27 and two analogs were more effective towards Gram-negative, and BMAP-28 towards Gram-positive organisms . In addition, BMAP-28 provided some protection in vitro against human herpes simplex virus type 1 (HSV-1) . The parent peptides and mBMAP-28 analog protected mice from lethal i.p . infections in an acute peritonitis model at peptide doses significantly lower than those toxic to the animals, suggesting a satisfactory therapeutic index. Peptides, 2003 Nov, 24(11), 1681 - 91 The relationship between peptide structure and antibacterial activity; Powers JP et al.; Cationic antimicrobial peptides are a class of small, positively charged peptides known for their broad-spectrum antimicrobial activity . These peptides have also been shown to possess anti-viral and anti-cancer activity and, most recently, the ability to modulate the innate immune response . To date, a large number of antimicrobial peptides have been chemically characterized, however, few high-resolution structures are available . Structure-activity studies of these peptides reveal two main requirements for antimicrobial activity, (1) a cationic charge and (2) an induced amphipathic conformation . In addition to peptide conformation, the role of membrane lipid composition, specifically non-bilayer lipids, on peptide activity will also be discussed. Peptides, 2003 Nov, 24(11), 1669 - 80 Molecular strategies in biological evolution of antimicrobial peptides; Nicolas P et al.; Gene-encoded antimicrobial peptides that protect the skin of hylid and ranin frogs against noxious microorganisms are processed from a unique family of precursor polypeptides with a unique pattern of conserved and variable regions opposite to that of conventional secreted peptides . Precursors belonging to this family, designated the preprodermaseptin, have a common N-terminal preproregion that is remarkably well conserved both within and between species, but a hypervariable C-terminal domain corresponding to antimicrobial peptides with very different lengths, sequences, charges and antimicrobial spectra . Each frog species has its own distinct panoply of 10-20 antimicrobial peptides so that the 5000 species of ranids and hylids may produce approximately 100,000 different peptide antibiotics . The strategy that these frogs have evolved to generate this enormous array of peptides includes repeated duplications of a 150 million years old ancestral gene, focal hypermutation of the antimicrobial peptide domain maybe involving a mutagenic DNA polymerase similar to Escherichia coli Pol V, and subsequent actions of positive (diversifying) selection . The hyperdivergence of skin antimicrobial peptides can be viewed as the successful evolution of a multi-drug defense system that provides frogs with maximum protection against rapidly changing microbial biota and minimizes the chance of microorganisms developing resistance to individual peptides . The impressive variations in the expression of frog skin antimicrobial peptides may be exploited for discovering new molecules and structural motifs targeting specific microorganisms for which the therapeutic armamentarium is scarce. Peptides, 2003 Nov, 24(11), 1655 - 67 Hagfish intestinal antimicrobial peptides are ancient cathelicidins; Uzzell T et al.; Three potent broad-spectrum antimicrobial peptides (HFIAP-1, -2, and -3) isolated from intestinal tissues of Myxine glutinosa (Atlantic hagfish) are identified as ancient members of the cathelicidin family of antimicrobial peptides, hitherto known only from mammals . In situ hybridization reveals that HFIAPs are produced in nests of myeloid cells within the loose connective tissue of the gut wall, a tissue reminiscent of both gut-associated lymphoid tissue (GALT) and vertebrate spleen . We suggest that this tissue organization provides local defense of the hagfish gastrointestinal tract via innate immunity and possibly served as the architectural plan upon which the adaptive immune system evolved. Peptides, 2003 Nov, 24(11), 1647 - 54 Evolution of primate theta-defensins: a serpentine path to a sweet tooth; Nguyen TX et al.; Retrocyclins (ancestral human theta-defensins) are cyclic antimicrobial octadecapeptides that interfere with viral uptake and protect human cells from infection by T- and M-tropic strains of HIV-1 in vitro . As are other theta-defensins, retrocyclins are lectins that bind gp120, CD4, and galactosylceramide-all of which are implicated in HIV-1 uptake . Although theta-defensin mRNA transcripts are present in human bone marrow, spleen, thymus, testis, and skeletal muscle, a premature stop codon aborts their translation . We found six theta-defensin (DEFT) genes in the human genome; five on chromosome 8p23 and one on chromosome 1 . All six of these pseudogenes, as well as their homologues in chimpanzees and gorillas, contained the same premature stop codon mutation . Whereas we found intact DEFT genes in DNA from several Old World Monkeys, Hylobates syndactylus (a lesser ape) and orangutans, no homologues were present in DNA from six New World Monkeys and five prosimians . We conclude that DEFT genes and theta-defensins arose in Old World Monkeys by mutation of a pre-existing alpha-defensin gene . Although intact DEFT genes survive in some nonhuman primates, our hominid ancestors lost their ability to produce theta-defensins after the orangutan and hominid lineages diverged . It is possible (but may be difficult to prove) that this mutation rendered our species more susceptible to infection by HIV-1. Eur J Pharm Biopharm, 2004 Mar, 57(2), 245 - 9 Polycomplexes of poly(acrylic acid) with streptomycin sulfate and their antibacterial activity; Nurkeeva ZS et al.; Complex formation between streptomycin sulfate and poly(acrylic acid) has been studied in aqueous solutions by turbidimetric, potentiometric and viscometric methods as well as by FTIR spectroscopy . It was shown that these polycomplexes are stabilized by electrostatic interactions . The solubility of polycomplexes was examined as a function of pH and it was found that at pH values below 3.1 the polycomplexes undergo complete dissociation or dissolution . The antimicrobial activity of the drug and its polycomplex was evaluated using Sarcina sp . as a model organism . It was demonstrated that the polycomplexes have an antimicrobial activity on the same level as the free drug. Biochem J, 2004 Jun 15, 380(Pt 3), 867 - 73 Kinetic and structural characterization of a product complex of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Escherichia coli; Garcon A et al.; HPPK (6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase) catalyses the transfer of pyrophosphate from ATP to HMDP (6-hydroxymethyl-7,8-dihydropterin), to form AMP and DHPPP (6-hydroxymethyl-7,8-dihydropterin pyrophosphate) . This transformation is a key step in the biosynthesis of folic acid, and HPPK is consequently a target for antimicrobial drugs . The substrates are known to bind to HPPK in an ordered manner, with ATP binding first followed by HMDP . In the present study we show by isothermal titration calorimetry that the product, DHPPP, can bind to the HPPK apoenzyme with high affinity (equilibrium dissociation constant, K(d)=0.2 microM), but without the enhancement of pterin fluorescence that occurs on binding of HMDP . The transient kinetics of the enzyme can be monitored by measuring the change in the fluorescence of the pterin ring using stopped-flow methods . The fluorescence exhibits a pronounced biphasic behaviour: it initially rises and then declines back to its original level . This behaviour is in agreement with a two-state kinetic model, with the first phase of fluorescence increase associated with HMDP binding to the enzyme, and the second phase with a slow event that occurs after the reaction has taken place . The HPPK-DHPPP and HPPK-DHPPP-AMP complexes were examined by NMR, and the binding site for DHPPP partially mapped from changes in chemical shifts identified from two dimensional 1H/15N heteronuclear single-quantum coherence spectra . The results demonstrate that DHPPP, in contrast to HMDP, is able to bind to the HPPK apoenzyme and suggest that the pyrophosphate moieties on the ligand play an important role in establishment of a high affinity binding site for the pterin ring. Infection, 2003 Dec, 31 Suppl 2, 16 - 21 Prevalence and patterns of antibiotic prescribing in Italian hospitals; Porretta A et al.; Use of antimicrobial drugs is associated with the emergence of resistant bacteria, increasing hospital expenditures and requires an assessment of appropriateness . The aim of this study was to investigate prevalence and patterns of antibiotic prescribing and expenditures in Italian hospitals . A prevalence survey was performed in 15 Italian hospitals . Data on antimicrobial use and expenditures in the year 2000 and 1-day point prevalence information on antibiotic prescription, type and sources of infections and expenditures were obtained through a review of pharmacy records and charts of 2,165 inpatients . 45.5% of the patients surveyed were receiving at least one antibiotic: 148 for hospital-acquired infections (HAI), 262 for community-acquired infections (CAI) . No active infection was recorded for 575 patients (58.4%) . 57.3% of prescriptions for HAI and 65.9% for CAI were based on empiric and presumptive criteria, while 39% of HAI and 15.8% of CAI were oriented by microbiology and susceptibility testing results . Guidelines were followed in choosing the antimicrobial drugs for 22.8% of therapeutic and 46.8% of prophylactic courses . High rates of antibiotic usage were observed in Italian hospitals . Areas for improvement, both for the use of diagnostic resources and the prescribing habits, were identified . The 1-day prevalence survey of antimicrobial use may be a tool of feedback to prescribers for more appropriate drug selection. Neurol Med Chir (Tokyo), 2004 Feb, 44(2), 86 - 9 Prolactinoma with a high adrenocorticotropic hormone level caused by meningitis--case report; Utsuki S et al.; A 69-year-old man was admitted semicomatose with high-grade fever and meningeal signs . Magnetic resonance imaging showed a supra- and intrasellar lesion . Hormone studies on admission showed increased serum prolactin, adrenocorticotropic hormone (ACTH), and cortisol titers . However, the serum ACTH and cortisol levels returned to normal after treatment of meningitis with an antimicrobial agent . The histological diagnosis was pituitary adenoma . Immunohistological staining showed positive reaction for prolactin but not for ACTH . This is a rare case of prolactinoma with a high serum ACTH level caused by meningitis. Z Naturforsch {C}, 2004 Jan-Feb, 59(1-2), 75 - 80 Composition and the in vitro antimicrobial activities of the essential oils of some Thymus species; Azaz AD et al.; The genus Thymus (Lamiaceae) is represented by 38 species (64 taxa) in Turkey, and 24 of which are endemic to Turkey . Aerial parts of Thymus longicaulis subsp . chaubardii var . chaubardii, T . zygioides var . lycaonicus, T . longicaulis subsp . longicaulis var . subisophyllus and T . pulvinatus collected from three different localities in Balikesir province were subjected to hydrodistillation to yield essential oils which were subsequently analysed by GC and GC/MS . The main constituents of the oils were identified, and antimicrobial bioassay was applied . Thymol (56.6%, 42.8%, 36.9%) was the main component in the oils of T . longicaulis subsp . chaubardii var . chaubardii (chemotype I), T . longicaulis subsp . chaubardii var . chaubardii (chemotype II) and T . zygioides var . lycaonicus respectively . The oil of T . longicaulis subsp . longicaulis var . subisophyllus contained carvacrol (60.0%) and the oil of T . pulvinatus borneol (27.9%) as main constituents. Dermatol Clin, 2004 Jan, 22(1), 63 - 71 Antimicrobial therapy and resistance in dermatologic pathogens of the elderly; Hutchison LC; Dermatologic infections are treated to improve the elderly patient's quality of life and prevent disability and death . Pharmacokinetic changes, social issues, and the risk for adverse effects and drug interactions, however, increase the challenge to achieve successful treatment of those over age 65 as compared with younger patients . This challenge grows ever larger when coupled with the increasing trends of resistance among bacteria and fungi . The clinician can effectively face this challenge through careful consideration of diagnosis, patient risk factors, antimicrobial pharmacology, and resistance patterns. Med Arh, 2003, 57(4 Suppl 1), 15 - 8 Prevention of nosocomial infections in ICU . What is really effective? Lepape A. In South East of France, about 20% of the ICU patients with a length of stay > or = 2 days will develop a nosocomial infection (NI) related to an invasive device . This elevated rates of NI (the most elevated in the hospital) are related to the usual severity of patients, the use of invasive devices such as indwelling arterial catheter, central venous catheter, intubation and bladder catheter . These two characteristics are associated with an important antimicrobial consumption and a subsequent selection of resistant bacteria . The techniques which could be used in the prevention of NI have now proved to be effective . They are hand disinfection, non sterile gloves utilization and a rationale use of mask, gowns . The application of these measures are known as Standard Precautions, recommended by the CDC . The specificity of prevention in ICU is questionable, since many measures can be applied in ICU, anesthesia or surgery . In the prevention of NI in ICU, without any doubt, the most important (but the most difficult to achieve) is the strict respect of standard precautions . To achieve this goal, the best investment is alcoholic hand rub . Among the specific measures, maximum barrier precaution for CVC insertion, reduction of indication and duration of invasive device exposure . The real challenge is to apply few effective measures, but accepted, associated with behavioural changes and whose compliance is measured. Clin Gastroenterol Hepatol, 2003 Jul, 1(4), 273 - 8 Pretreatment antimicrobial susceptibility testing is cost saving in the eradication of Helicobacter pylori; Romano M et al.; BACKGROUND & AIMS: The major obstacle to 100% effective eradication of Helicobacter pylori infection is represented by antimicrobial-resistant H . pylori strains . This randomized study was designed to evaluate whether regimens based on pretreatment susceptibility testing were more effective and cost saving compared with standard nonsusceptibility testing-based therapy in the eradication of H . pylori infection . METHODS: We studied 150 consecutive H . pylori-infected dyspeptic subjects . Patients were randomly assigned to omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily for 7 days or to omeprazole 20 mg twice daily and 2 antimicrobials chosen based on susceptibility testing . H . pylori status was reevaluated 12 weeks after the end of treatment by the (13)C-urea breath test . RESULTS: Susceptibility testing-based regimens led to the following results . (1) Eradication rates were 97.3% (95% confidence interval {CI}, 91.2%-99.5%) (71 of 73) and 94.6% (95% CI, 87.6%-98.3%) (71 of 75) in the per-protocol and intention-to-treat analysis, respectively . These were significantly higher (P < 0.005) than eradication rates obtained without susceptibility testing, that is, 79.4% (95% CI, 69.1%-87.6%) (58 of 73) and 77.3% (95% CI, 66.9%-85.7%) (58 of 75) in the per-protocol and intention-to-treat analyses, respectively . (2) There were savings of approximately $5 U.S . per patient compared with standard triple therapy . CONCLUSIONS: Pretreatment antimicrobial susceptibility testing is more effective and cost saving and, in health systems that confirm cost advantage, microbial susceptibility testing should be routinely used for eradication of H . pylori infection. J Med Microbiol, 2004 Apr, 53(Pt 4), 281 - 5 Further characterization of porcine Brachyspira hyodysenteriae isolates with decreased susceptibility to tiamulin; Karlsson M et al.; Brachyspira hyodysenteriae is the causative agent of swine dysentery, a severe diarrhoeal disease in pigs . Few drugs are available to treat the disease, owing to both antimicrobial resistance and withdrawal of drugs authorized for use in pigs . Tiamulin is the drug of choice in many countries, but isolates with decreased susceptibility have recently been reported . The mechanism of tiamulin resistance in B . hyodysenteriae is not known and this facet is essential to understand the dissemination of the trait . To study the resistance epidemiology of B . hyodysenteriae, further characterization of a set of isolates from Germany (n = 16) and the UK (n = 6) with decreased susceptibility to tiamulin was performed . The relatedness between the isolates was studied by comparing PFGE patterns, and the in vitro susceptibility to five other antimicrobials (aivlosin, doxycycline, salinomycin, chloramphenicol and avilamycin) was also determined . For comparison of the antimicrobial-susceptibility pattern, Swedish (n = 20) and British (n = 4) tiamulin-susceptible isolates were tested . The German isolates represented several different PFGE patterns, indicating that tiamulin usage has been sufficient to select clones with decreased tiamulin susceptibility at different farms in Germany . The PFGE pattern for the six British isolates with decreased tiamulin susceptibility was identical to that of the German isolates, and they had a similar antimicrobial-susceptibility pattern, except for resistance to aivlosin, which was only found in a few German isolates . No other co-resistance with tiamulin was found. Cell Biol Toxicol, 2003 Nov, 19(6), 339 - 53 Determination of safety levels of horseradish peroxidase-iodide system to human gingival keratinocytes and fibroblasts in vitro; Ihalin R et al.; The peroxidase-iodide (I-) system is a potential antimicrobial agent, and its bacteriocidal activity against various periodontal bacteria has been shown in many studies . The aim of this study was to investigate the possible cytotoxic effects of a non-physiological horseradish peroxidase (HRP)-I- system on human gingival keratinocytes and fibroblasts . Immortalized human skin keratinocyte cell line was used as a reference . Three indicators were studied: membrane permeability (trypan blue staining), cell growth (crystal violet staining) and metabolic activity (alamarBlue stain) . The cells were cultured in microtitration plates, and the most commonly used exposure time to the HRP system was 1 h . The effects of HRP system on cell growth and metabolic activity were observed at lower I- and H2O2 concentrations than its effects on membrane permeability . Gingival fibroblasts were more prone to detachment than keratinocyte cell lines, but no differences in changes of growth or metabolic activities were observed between gingival fibroblasts and gingival keratinocytes . The highest concentrations of the HRP-I- system components which did not have any significant detrimental effects on the metabolic activity and cell growth of gingival keratinocytes and fibroblasts were: 50 microg/ml HRP, 500 micromol/L I- and 500 micromol/L H2O2 . Although this system has been shown to be antibacterial against oral bacteria, no recommendations about the usage of the HRP-I- system in oral cavity can be made yet due to the in vitro nature of this study . Our results form the basis for future safety studies investigating the chronic toxicity of this system to oral epithelium. Eur J Clin Microbiol Infect Dis, 2004 Apr, 23(4), 271 - 88 Epub 2004 Mar 10. Pharmacokinetic and pharmacodynamic issues in the treatment of bacterial infectious diseases; McKinnon PS et al.; This review outlines some of the many factors a clinician must consider when selecting an antimicrobial dosing regimen for the treatment of infection . Integration of the principles of antimicrobial pharmacology and the pharmacokinetic parameters of an individual patient provides the most comprehensive assessment of the interactions between pathogen, host, and antibiotic . For each class of agent, appreciation of the different approaches to maximize microbial killing will allow for optimal clinical efficacy and reduction in risk of development of resistance while avoiding excessive exposure and minimizing risk of toxicity . Disease states with special considerations for antimicrobial use are reviewed, as are situations in which pathophysiologic changes may alter the pharmacokinetic handling of antimicrobial agents. J Antimicrob Chemother, 2004 Apr, 53(4), 650 - 2 Epub 2004 Mar 10. Documentation of antibiotic prescribing controls in UK NHS hospitals; Woodford EM et al.; OBJECTIVES: To identify the types, prevalence and nature of antibiotic prescribing control documents within NHS hospitals in the UK . METHODS: A self-completion postal questionnaire was sent to each Chief Pharmacist at 465 NHS hospitals in 2001/2002 . This contained questions covering hospital demographics, and hospital antibiotic prescribing control documentation, including format, dissemination, approval and review processes . RESULTS: In total, 253 (54%) completed questionnaires were returned . Of these, 168 respondents' hospitals had an antibiotic formulary, 107 had a policy for antibiotic prescribing and 216 had guidelines on antibiotic use . All three types of antibiotic prescribing documents were used by 82 hospitals but 18 did not have any documents; 44% of formularies, 45% of policies and 35% of guidelines were available electronically . The Drug and Therapeutics Committee was the most frequently cited body for document approval and approximately one-third of documents had been approved during the current year of the questionnaire . Only about one-half of responding hospitals had an annual review of documents . CONCLUSIONS: Despite publication of high-profile national guidance in response to growing concerns regarding antimicrobial resistance, there has been little increase in the use of antibiotic prescribing control documents in NHS hospitals over the past decade . It is clear that appropriate controls for antibiotic prescribing are not yet universally applied in the UK and recommendations for action have been proposed. FEBS Lett, 2004 Mar 12, 561(1-3), 117 - 21 MEF up-regulates human beta-defensin 2 expression in epithelial cells; Lu Z et al.; Human beta-defensin 2 (HBD2), an antimicrobial peptide, is widely expressed in epithelial tissues and displays a potent killing activity in response to the invasiveness of a wide range of microorganisms and the stimulation of various molecules . Myeloid ELF-1-like factor (MEF) has been reported to be involved in innate immunity responses, such as activation of perforin and lysozyme transcription . The role of MEF in the transcription regulation of HBD2, however, is unknown . Here, we show that MEF not only activated HBD2 promoter activity, but also increased the endogenous HBD2 transcription level . Moreover, the activated HBD2 promoter activity was attenuated by the antisense MEF RNA input and the loss of the ETS binding site (EBS: GGAA core sequence) in the HBD2 promoter . The interaction between the EBS and MEF protein was further confirmed by electrophoretic mobility shift assay . Thus, our data indicate that MEF may play an important role in regulating HBD2 expression in epithelial cells. J Control Release, 2004 Feb 20, 95(1), 67 - 74 New vesicular ampicillin-loaded delivery systems for topical application: characterization, in vitro permeation experiments and antimicrobial activity; Carafa M et al.; In this paper, the experimental conditions for preparing ampicillin-loaded surfactant vesicles (SVs) are described . Our studies are focused on the potential use of a vesicular polymeric dispersion as ampicillin delivery system for topical application . The main components of the formulation are uncharged and charged SVs loaded with ampicillin and dispersed in a gellan solution . The following issues are addressed: the drug encapsulation efficiency (e.e.), the kinetic of drug release from the delivery systems, the antimicrobial activity of vesicle-entrapped ampicillin . The in vitro permeation experiments through a synthetic lipophilic barrier (Silastic) and through porcine skin are carried out to evaluate the potential use as a dermal formulation . The use of both a synthetic and a biological membrane allows to discriminate between the effects related to variations of thermodynamic parameters and those correlated to biological factors . The release rate of ampicillin is increased by encapsulation in neutral and negatively charged SVs and the permeation rate was slowed by dispersion of drug-loaded SVs in gellan solution . Finally, studies of antimicrobial activity on prepared systems evidenced that ampicillin encapsulated in SVs exhibit a higher activity than the free drug. J Ethnopharmacol, 2004 Feb, 90(2-3), 353 - 7 In vitro antimicrobial activity of certain medicinal plants from eastern Ghats, India, used for skin diseases; Jeevan Ram A et al.; The paper deals with ethnopharmacological and antimicrobial properties of certain medicinal plants used by adivasi tribes of the Eastern Ghats of Andhra Pradesh, India . Ethanolic extracts of 23 crude drug samples used for various skin diseases were assayed for antimicrobial activity against four bacterial and one fungal human pathogens. J Ethnopharmacol, 2004 Feb, 90(2-3), 205 - 15 Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle (Urtica dioica L.); Gulcin I et al.; In this study, water extract of nettle (Urtica dioica L.) (WEN) was studied for antioxidant, antimicrobial, antiulcer and analgesic properties . The antioxidant properties of WEN were evaluated using different antioxidant tests, including reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities . WEN had powerful antioxidant activity . The 50, 100 and 250 microg amounts of WEN showed 39, 66 and 98% inhibition on peroxidation of linoleic acid emulsion, respectively, while 60 microg/ml of alpha-tocopherol, exhibited only 30% inhibition . Moreover, WEN had effective reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities at the same concentrations . Those various antioxidant activities were compared to standard antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), quercetin, and alpha-tocopherol . In addition, total phenolic compounds in the WEN were determined as pyrocatechol equivalent . WEN also showed antimicrobial activity against nine microorganisms, antiulcer activity against ethanol-induced ulcerogenesis and analgesic effect on acetic acid-induced stretching. Annu Rev Entomol, 1996, 41, 353 - 74 Semiochemical parsimony in the Arthropoda; Blum MS; A wide variety of arthropods have adapted their own semiochemicals to subserve multiple functions in diverse contexts . Semiochemicals, the pheromones and allomones, have been detected in arthropod species in six orders, and it has been clearly established that these compounds are used with great parsimony . The versatility of these invertebrates in using these natural products for an incredible diversity of functions emphasizes the significance of semiochemicals in the evolutionary biology of Arthropoda . Multifunctional pheromones have proved to be especially characteristic of the queens of eusocial species . Compounds such as the queen substance of the honey bee, Apis mellifera, possess unrelated primer and releaser functions for the workers and act as a sex attractant for drones . Females of other hymenopterous species exploit the secretions of sting-associated glands as sex pheromones, whereas a variety of nonhymenopterous species have adapted components in diverse defensive secretions to function as sex pheromones . The alarm pheromones of many arthropods are also used as defensive allomones, activity inhibitors, cryptic alarm pheromones, aggregative attractants, robbing agents, digging agents, trail pheromones, and antimicrobial agents . Defensive allomones also possess some of these parsimonious roles; in addition, however, some of these compounds possess highly distinctive roles, such as functioning as lethal attractants for prey, or, in he aquatic milieu, cuticular wetting agents . Clearly, the availability of a variety of pheromones and allomones has enabled arthropods to evolve an elegant semiochemical parsimony with which to exploit the biological milieu. Annu Rev Plant Physiol Plant Mol Biol, 1998 Jun, 49, 727 - 760 FROM VACUOLAR GS-X PUMPS TO MULTISPECIFIC ABC TRANSPORTERS; Rea PA et al.; While the concept of H+-coupling has dominated studies of energy-dependent organic solute transport in plants for over two decades, recent studies have demonstrated the existence of a group of organic solute transporters, belonging to the ATP-binding cassette (ABC) superfamily, that are directly energized by MgATP rather than by a transmembrane H+-electrochemical potential difference . Originally identified in microbial and animal cells, the ABC superfamily is one of the largest and most widespread protein families known . Competent in the transport of a broad range of substances including sugars, peptides, alkaloids, inorganic anions, and lipids, all ABC transporters are constituted of one or two copies each of an integral membrane sector and cytosolically oriented ATP-binding domain . To date, two major subclasses, the multidrug resistance-associated proteins (MRPs) and multidrug resistance proteins (MDRs) (so named because of the phenotypes conferred by their animal prototypes), have been identified molecularly in plants . However, only the MRPs have been defined functionally . This review therefore focuses on the functional capabilities, energetics, organization, and regulation of the plant MRPs . Otherwise known as GS-X pumps, or glutathione-conjugate or multispecific organic anion Mg2+-ATPases, the MRPs are considered to participate in the transport of exogenous and endogenous amphipathic anions and glutathionated compounds from the cytosol into the vacuole . Encoded by a multigene family and possessing a unique domain organization, the types of processes that likely converge and depend on plant MRPs include herbicide detoxification, cell pigmentation, the alleviation of oxidative damage, and the storage of antimicrobial compounds . Additional functional capabilities might include channel regulation or activity, and/or the transport of heavy metal chelates . The identification of the MRPs, in particular, and the demonstration of a central role for ABC transporters, in general, in plant function not only provide fresh insights into the molecular basis of energy-dependent solute transport but also offer the prospect for manipulating and investigating many fundamental processes that have hitherto evaded analysis at the transport level. Am Surg, 2004 Feb, 70(2), 137 - 40; discussion 140 Open abdomen management of intra-abdominal sepsis; Adkins AL et al.; Despite surgical advances, antimicrobial therapy, and intensive care, the morbidity and mortality of intra-abdominal sepsis remains high . The primary purpose of this study was to determine whether open abdomen management of intra-abdominal sepsis reduces intensive care unit (ICU) and hospital mortality . The records of 81 consecutive patients with open abdomen management for intra-abdominal sepsis admitted to the surgical ICU from January 1998 to April 2002 were retrospectively reviewed . Outcomes were compared to a historical control group with primary abdominal closure, also admitted to the surgical ICU with intra-abdominal sepsis and matched for sex, age, source of sepsis, and APACHE III score . ICU mortality for the open abdomen group was 25 per cent versus 17 per cent for the control group . Hospital mortality was 33 per cent and 25 per cent for the open abdomen patients and historical controls, respectively . Both ICU and hospital length of stay were significantly longer for the open abdomen group . An overall fistula rate of 14.8 per cent was demonstrated in the open abdomen patients . A significant difference in overall ICU and hospital mortality was not demonstrated between patients treated with open abdomen management and historical controls . A prospective randomized study accounting for extent of sepsis may define a role for open abdomen management in selected subgroups of patients. J Hist Med Allied Sci, 2004 Jan, 59(1), 50 - 89 The history of gold therapy for tuberculosis; Benedek TG; This is a historical study of the popularization of a medical therapy contrary to pertinent experimental findings . Presumably this circumstance reflects the desperation about tuberculosis: highly prevalent, highly fatal, and lacking any etiologically directed therapy . Gold compounds were introduced, based initially on the reputation of Robert Koch, who had found gold cyanide effective against M . tuberculosis in cultures, but not in experimentally infected animals . Treatment of pulmonary tuberculosis with these compounds was popularized, particularly by Danish physicians, in the mid-1920s, despite consistently negative experimental results, based on Paul Ehrlich's theories of antimicrobial drug effects . Difficulties in the design of interpretable clinical studies were soon recognized but also generally ignored, thus permitting data to be interpreted as favorable to antituberculous gold therapy . Eventually toxicity was considered to outweigh the alleged therapeutic benefit of all gold compounds . This resulted in their discard shortly before the introduction of streptomycin therapy. Curr Treat Options Gastroenterol, 2004 Apr, 7(2), 111 - 117 AIDS Cholangiopathy; Yusuf TE et al.; AIDS is an advanced disease with systemic and infectious complications that can be fatal . When a patient with AIDS presents with right upper quadrant or midepigastric pain, cholestasis, and symptoms of cholangitis, AIDS cholangiopathy should be suspected and appropriate diagnostic and therapeutic interventions should be initiated . Opportunistic infections such as Cryptosporidium and cytomegalovirus are the most common cause of AIDS cholangiopathy . Four distinct cholangiographic abnormalities have been demonstrated by endoscopic retrograde cholangiopancreatography, the most common being papillary stenosis with sclerosing cholangitis . Antimicrobial therapy is often ineffective . Highly active antiretroviral therapy may enhance immune function and offers the best medical therapy to clear the opportunistic infections . Ursodeoxycholic acid has a limited benefit in patients with sclerosing cholangitis and cholestasis . Endoscopic sphincterotomy has been shown to relieve pain and biliary obstruction in patients with papillary stenosis . Balloon dilation of strictures and stent placement decompress the biliary system and may be helpful . Cholecystectomy is recommended to treat acalculous cholecystitis, and celiac plexus block may be offered to patients with terminal disease and intractable abdominal pain. J Pept Res, 2004 Feb, 63(2), 69 - 84 Effects of single D-amino acid substitutions on disruption of beta-sheet structure and hydrophobicity in cyclic 14-residue antimicrobial peptide analogs related to gramicidin S; Lee DL et al.; Gramicidin S (GS) is a 10-residue cyclic beta-sheet peptide with lytic activity against the membranes of both microbial and human cells, i.e . it possesses little to no biologic specificity for either cell type . Structure-activity studies of de novo-designed 14-residue cyclic peptides based on GS have previously shown that higher specificity against microbial membranes, i.e . a high therapeutic index (TI), can be achieved by the replacement of a single L-amino acid with its corresponding D-enantiomer {Kondejewski, L.H . et al . (1999) J . Biol . Chem . 274, 13181} . The diastereomer with a D-Lys substituted at position 4 caused the greatest improvement in specificity vs . other L to D substitutions within the cyclic 14-residue peptide GS14, through a combination of decreased peptide amphipathicity and disrupted beta-sheet structure in aqueous conditions {McInnes, C . et al . (2000) J . Biol . Chem . 275, 14287} . Based on this information, we have created a series of peptide diastereomers substituted only at position 4 by a D- or L-amino acid (Leu, Phe, Tyr, Asn, Lys, and achiral Gly) . The amino acids chosen in this study represent a range of hydrophobicities/hydrophilicities as a subset of the 20 naturally occurring amino acids . While the D- and L-substitutions of Leu, Phe, and Tyr all resulted in strong hemolytic activity, the substitutions of hydrophilic D-amino acids D-Lys and D-Asn in GS14 at position 4 resulted in weaker hemolytic activity than in the L-diastereomers, which demonstrated strong hemolysis . All of the L-substitutions also resulted in poor antimicrobial activity and an extremely low TI, while the antimicrobial activity of the D-substituted peptides tended to improve based on the hydrophilicity of the residue . D-Lys was the most polar and most efficacious substitution, resulting in the highest TI . Interestingly, the hydrophobic D-amino acid substitutions had superior antimicrobial activity vs . the L-enantiomers although substitution of a hydrophobic D-amino acid increases the nonpolar face hydrophobicity . These results further support the role of hydrophobicity of the nonpolar face as a major influence on microbial specificity, but also highlights the importance of a disrupted beta-sheet structure on antimicrobial activity. Br J Haematol, 2004 Mar, 124(6), 777 - 86 Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis; Srinivasan R et al.; Approximately 15% of patients undergoing non-myeloablative allogeneic haematopoietical cell transplantation (NMHCT) develop steroid-refractory acute-graft versus host disease (aGVHD), a usually fatal complication . We encountered 18 cases of steroid-refractory aGVHD in 146 patients, undergoing NMHCT from a related human leucocyte antigen-compatible donor following cyclophosphamide/fludarabine-based conditioning . Our initial cohort of steroid-refractory aGVHD patients treated with antithymocyte globulin (ATG) and mycophenolate mofetil (regimen-1: n = 6) had high GVHD-related mortality . Therefore, we investigated an alternative strategy for subsequent patients developing this complication (regimen-2: n = 12), consisting of daclizumab (alone or combined with infliximab/ATG) and targeted broad spectrum antibacterial and aspergillus prophylaxis in conjunction with rapid tapering of steroids to minimize opportunistic infections . In a retrospective analysis, patients receiving regimen-2 were significantly more likely to have complete resolution of GVHD compared with those receiving regimen-1 {12/12 (100%) vs . 1/6 (17%); P < 0.001} . When compared with those receiving regimen-1, regimen-2 patients also had a higher probability of survival at day 100 (100% vs . 50%) and day 200 (73% vs . 17%) post-transplant, and improved overall survival (median 453 d vs . 42 d from aGVHD onset; P < 0.0001) . GVHD-related mortality was 89% for regimen-1 patients vs . 17% for regimen-2 patients (P < 0.0001) . These data suggest that a co-ordinated approach using immunoregulatory monoclonal antibodies, pre-emptive antimicrobial therapy and judicious steroid withdrawal can dramatically improve outcome in steroid-refractory aGVHD. Infect Dis Clin North Am, 2003 Dec, 17(4), 727 - 37, vi Antimicrobial treatment of hospital-acquired pneumonia; Chastre J; Rapid identification of infected patients and accurate selection of antimicrobial agents for initial treatment of hospital-acquired pneumonia represent important clinical goals, because it seems that better treatment of this infection might have a major impact on hospital-associated mortality and morbidity . Persistently high mortalities for pneumonia in the critical care unit argue, however, for a continued reassessment of the current modalities of therapy and definition of better protocols . More active and less toxic antibacterial agents are still needed . It should be emphasized that in the event that one or several specific etiologic agents are identified by a reliable technique, the choice of antimicrobial drugs is much easier, because the optimal treatment may be selected in light of the susceptibility pattern of the causative pathogens without resorting to broad-spectrum drugs or risking inappropriate treatment . Great efforts should be placed to obtain reliable pulmonary specimens for direct microscopic examination and cultures in each patient clinically suspected of having developed nosocomial pneumonia before new antibiotics are administered. Infect Dis Clin North Am, 2003 Dec, 17(4), 717 - 26 Hospital-acquired pneumonia: diagnostic strategies: lessons from clinical trials; Fagon JY; It should be emphasized that, for the management of VAP, like for all infectious diseases, the choice of antimicrobial treatment is much easier when the specific etiologic agents are identified by a reliable diagnostic technique . Before new antibiotics are administered, reliable pulmonary specimens (chosen according to the literature and within the capabilities of the local microbiology laboratory) must be obtained for direct examination and cultures from patients clinically suspected of having developed VAP. Infect Dis Clin North Am, 2003 Dec, 17(4), 707 - 16 Diagnosis of hospital-acquired pneumonia: postmortem studies; Nseir S et al.; Postmortem human and animal studies provided important insights into the relationship between histology and bacteriology in VAP . According to the results of these studies, VAP is a multifocal and polymicrobial infectious process . The lesions are predominately located in dependent segments of lower lobes . There is no straightforward relationship between the intensity of lung damage and the local microbial burden . Histobacteriologic discrepancy may explain why even such techniques as PSB and BAL can be unreliable for the diagnosis of VAP . The histopathologic examination of the lung tissue has been traditionally regarded as the gold standard for diagnosis of VAP . Even with histology, however, pneumonia is frequently difficult to define . For daily practice, antimicrobial decisions and the guidance of antimicrobial regimens should not rely exclusively on the results of quantitative cultures in the individual patient . Instead, finding a balance between clinical judgment and microbiologic results is crucial to manage patients with VAP appropriately. Int J Prosthodont, 2004 Jan-Feb, 17(1), 65 - 71 Effects of a chemical disinfectant on the physical properties of dental stones; Hall BD et al.; PURPOSE: This study compared the effects of an antimicrobial agent (Asepto-Sol) on the physical properties of types III, IV, and V gypsum casts made from two types of impression materials . MATERIALS AND METHODS: Selected physical properties of five gypsum-based dental stones (Prima-Rock, Ortho Stone, New Fujirock, Die-Keen, Microstone) and two resin-based dental stones (Resin-Rock, Instone) were evaluated using an addition silicone impression material (Reprosil) and an irreversible hydrocolloid (Jeltrate Plus) . In group 1, Asepto-Sol solution replaced water as the gauging liquid for the seven dental stones . The mixed gypsum was poured directly onto impressions of two master dies using two impression materials . In group 2, impressions made with both impression materials were sprayed with the Asepto-Sol solution, left for 10 minutes, rinsed for 30 seconds with tap water, and poured with each dental stone mixed with deionized water . In group 3 (control), the gypsums were mixed with deionized water and the mixed stone was poured directly into impressions, with no exposure to Asepto-Sol . The physical properties evaluated for the gypsum specimens were linear dimensional change, detail reproduction, Knoop hardness, and transverse strength . RESULTS: The linear dimensional stability, detail reproduction, and transverse strength tests were relatively unaffected by the use of Asepto-Sol, with few exceptions . Detail reproduction appeared to be least affected by Asepto-Sol, and changes in Knoop hardness were noted but results differed among the seven dental stones . However, New Fujirock was not ideally matched with Jeltrate Plus, and no stone specimens could be produced . CONCLUSION: Whether mixed with the gypsum powder or sprayed on impressions, Asepto-Sol solution did not adversely affect the physical properties of the dental stones tested. Pneumologie, 2004 Mar, 58(3), 160 - 4 {Ranking of the polymerase chain reaction (PCR) and of other amplification methods in the diagnosis of tuberculosis}; Pfyffer GE; Worldwide, tuberculosis (TB) remains one of the leading infectious diseases, accounting for nearly 3 million deaths and more than 8 million new cases annually . Among them are 3.2 % multidrug-resistant strains of Mycobacterium tuberculosis . In the control of the spread of TB clinical mycobacteriology laboratories play an essential role providing the clinicians with timely detection, isolation, identification, and drug susceptibility testing results for M . tuberculosis . In the past twenty years numerous molecular techniques have been introduced to comply with the obvious needs for a reliable and rapid diagnosis of the disease . Nucleic acid amplification-based assays, in particular, the polymerase chain reaction (PCR), allow (i) direct detection of M . tuberculosis complex in clinical specimens; (ii) identification of mycobacteria; (iii) detection of resistance of M . tuberculosis to antimicrobial agents; and (iv) DNA typing to answer questions such as reactivation of disease or exogenous reinfection, and to track transmission and internal laboratory contaminations. Orthopade, 2004 Mar, 33(3), 267 - 72 {Classification and microbiology of osteomyelitis}; Zimmerli W et al.; The clinical presentation of osteomyelitis is multifarious . Therefore, patients are diagnosed and treated by various specialists with many different concepts of optimal management . Originally, only the acute and the chronic presentations were differentiated . The classification of Waldvogel, which is based on pathogenetic mechanisms, is more sophisticated . Diabetic foot is classified according to Wagner, who takes into account the continuous progression from sore to ulcer to osteomyelitis to gangrene . The staging according to Cierny-Mader is the most useful for the therapeutic management by surgeons . The spectrum of microorganisms is variable according to the type of osteomyelitis, epidemiology, age of the patient, co-morbidity, microbiological technique (culture, PCR), and duration of the infection . S . aureus is the leading pathogen in each type of osteomyelitis . Over the past 20 years, antimicrobial resistance has become an increasing problem . In case of osteomyelitis, standard susceptibility testing can be inaccurate . In case of device-related infection or in any type of chronic osteomyelitis, antimicrobial agents must be efficacious on stationary-phase and adhering microorganisms . Microbiologic culture and susceptibility testing should always be performed, in order to optimize the antimicrobial therapy. Chest, 2004 Mar, 125(3), 953 - 64 Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis; Wilson R et al.; STUDY OBJECTIVES: To compare the effectiveness of oral moxifloxacin with standard antibiotic therapy in acute exacerbation of chronic bronchitis (AECB) . DESIGN: Multicenter, multinational, randomized, double-blind study of two parallel treatment arms . PATIENTS: Outpatients >or= 45 years old with stable chronic bronchitis, smoking history of >or= 20 pack-years, two or more AECBs in the previous year, and FEV(1) < 85% of predicted value . Patients were enrolled when in a stable condition, and patients with exacerbations within 12 months of enrollment were randomized . INTERVENTIONS: Randomization (stratified on steroid use) between moxifloxacin (400 mg qd for 5 days) and standard therapy (amoxicillin {500 mg tid for 7 days}, clarithromycin {500 mg bid for 7 days}, or cefuroxime-axetil {250 mg bid for 7 days}) . MEASUREMENTS: Assessment at enrollment, randomization (Anthonisen type 1 exacerbation), 7 to 10 days after treatment, and monthly until next AECB or up to 9 months . The primary efficacy variable was clinical success (sufficient improvement, no alternative antimicrobial therapy required) 7 to 10 days after therapy . Secondary predefined end points were clinical cure (return to pre-exacerbation status), further antimicrobial use, time to next AECB, and bacteriologic success . RESULTS: Three hundred fifty-four patients received moxifloxacin, and 376 patients received standard therapy . At 7 to 10 days after therapy, clinical success rates were similar in intention-to-treat (ITT) patients (95% confidence interval {CI}, - 0.7 to 9.5) and per-protocol (PP) patients (95% CI, - 3.0 to 8.5) . Moxifloxacin showed superior clinical cure rates over standard therapy in both ITT patients (95% CI, 1.4 to 14.9) and PP patients (95% CI, 0.3 to 15.6), and higher bacteriologic success in microbiologically valid patients (95% CI, 0.4 to 22.1) . Fewer ITT patients required antimicrobials after treatment with moxifloxacin than standard therapy (p < 0.01) . Time to next exacerbation was longer with moxifloxacin; median and mean times to new AECBs in ITT patients who did not require any further antibiotics were 131.0 days and 132.8 days in moxifloxacin, and 103.5 days and 118.0 days in standard therapy, respectively (p = 0.03) . The occurrence of failure, new exacerbation, or any further antibiotic was less frequent in moxifloxacin-treated patients for up to 5 months of follow-up (p = 0.03) . CONCLUSIONS: Moxifloxacin was equivalent to standard therapy for clinical success and showed superiority over standard therapy in clinical cure, bacteriologic eradication, and long-term outcomes. Br J Pharmacol, 2004 Apr, 141(7), 1131 - 40 Epub 2004 Mar 08. A critical 'threshold' of beta 2-integrin engagement regulates augmentation of cytokine-mediated superoxide anion release; Walker TR et al.; 1 . Neutrophil adhesion regulates a number of processes involved in the pathogenesis of inflammatory diseases including rheumatoid arthritis . Neutrophil destructive potential can be modulated by adhesion, allowing alteration of inflammatory cell behaviour while preserving antimicrobial defences . beta(2)-Integrin-mediated neutrophil adhesion to albumin-coated latex beads (ACLB) allows modulation of integrin clustering and ligation and analysis of the effects of adhesion on neutrophil responses . Tumour necrosis factor-alpha (TNF alpha) enhanced neutrophil binding of different diameter ACLB equally, by almost four-fold, and independently of bead size . Adhesion of neutrophils to ACLB caused a size-dependent generation and release of O(2)(-) and also potentiated TNF alpha-induced O(2)(-) release . 2 . Binding of ACLB was not affected by disruption of cytoskeletal integrity with nocodazole or cytochalasin D or following blockade of tyrosine kinase activity . In contrast, tyrosine phosphorylation and an intact cytoskeleton were essential for adhesion- and cytokine-induced O(2)(-) release from neutrophils . Inhibition of adhesion- and cytokine-induced O(2)(-) release by 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazol{3,4-d}pyrimidine (PP2) indicated that a Src-family tyrosine kinase was the principal regulatory pathway mediating this response in neutrophils, a distal role for p38 MAPK was revealed by use of SB203580 . 3 . Tyrosine phosphorylation of c-Fgr, a Src-family tyrosine kinase, occurred following ACLB adhesion and exposure to TNF alpha, and was susceptible to inhibition by PP2 . We suggest that activation of the key regulatory enzyme c-Fgr is achieved following ligation of a critical threshold of integrins following binding of large (>3 microM) ACLB. Arch Intern Med, 2004 Mar 8, 164(5), 502 - 8 Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia; Roson B et al.; BACKGROUND: Early failure is a matter of great concern in the treatment of community-acquired pneumonia . However, information on its causes and risk factors is lacking . METHODS: Observational analysis of a prospective series of 1383 nonimmunosuppressed hospitalized adults with community-acquired pneumonia . Early failure was defined as lack of response or worsening of clinical or radiologic status at 48 to 72 hours requiring changes in antibiotic therapy or invasive procedures . Concordance of antimicrobial therapy was examined for cases with an etiologic diagnosis . RESULTS: At 48 to 72 hours, 238 patients (18%) remained febrile, but most of them responded without further changes in antibiotic therapy . Eighty-one patients (6%) had early failure . The main causes of early failure were progressive pneumonia (n = 54), pleural empyema (n = 18), lack of response (n = 13), and uncontrolled sepsis (n = 9) . Independent factors associated with early failure were older age (>65 years) (odds ratio {OR}, 0.35), multilobar pneumonia (OR, 1.81), Pneumonia Severity Index score greater than 90 (OR, 2.75), Legionella pneumonia (OR, 2.71), gram-negative pneumonia (OR, 4.34), and discordant antimicrobial therapy (OR, 2.51) . Compared with treatment responders, early failures had significantly higher rates of complications (58% vs 24%) and overall mortality (27% vs 4%) (P<.001 for both) . CONCLUSIONS: Early failure is infrequent but is associated with high morbidity and mortality rates . Its detection and management require careful clinical assessment . Most cases occur because of inadequate host-pathogen responses . Discordant therapy is a less frequent cause of failure, which may be preventable by rational application of the current antibiotic guidelines. Appl Environ Microbiol, 2004 Mar, 70(3), 1749 - 57 Elucidation of the antibacterial mechanism of the Curvularia haloperoxidase system by DNA microarray profiling; Hansen EH et al.; A novel antimicrobial enzyme system, the Curvularia haloperoxidase system, was examined with the aim of elucidating its mechanism of antibacterial action . Escherichia coli strain MG1655 was stressed with sublethal concentrations of the enzyme system, causing a temporary arrest of growth . The expression of genes altered upon exposure to the Curvularia haloperoxidase system was analyzed by using DNA microarrays . Only a limited number of genes were involved in the response to the Curvularia haloperoxidase system . Among the induced genes were the ibpA and ibpB genes encoding small heat shock proteins, a gene cluster of six genes (b0301-b0306) of unknown function, and finally, cpxP, a member of the Cpx pathway . Knockout mutants were constructed with deletions in b0301-b0306, cpxP, and cpxARP, respectively . Only the mutant lacking cpxARP was significantly more sensitive to the enzyme system than was the wild type . Our results demonstrate that DNA microarray technology cannot be used as the only technique to investigate the mechanisms of action of new antimicrobial compounds . However, by combining DNA microarray analysis with the subsequent creation of knockout mutants, we were able to pinpoint one of the specific responses of E . coli--namely, the Cpx pathway, which is important for managing the stress response from the Curvularia haloperoxidase system. Int Dent J, 2004 Feb, 54(1), 3 - 14 Topical and systemic antibiotics in the management of periodontal diseases; Mombelli A et al.; Both systemic and topical antibiotics are increasingly used in the management of periodontal infections . Whilst these drugs are used mostly on an empirical basis, some contend that rational use of antibiotics should be the norm due to their wide abuse and consequential global emergence of antibiotic resistance organisms . Here we review the rationale and principles of antimicrobial therapy, treatment goals, drug delivery routes and various antibiotics that are used in the management of periodontal diseases . The pros and cons of systemic and local antibiotic therapy are described together with practical guidelines for their delivery . The available data indicate, in general, that mechanical periodontal treatment alone is adequate to ameliorate or resolve the clinical condition in most cases, but adjunctive antimicrobial agents, delivered either locally or systemically, can enhance the effect of therapy in specific situations . This is particularly true for aggressive (early onset) periodontitis, in patients with generalised systemic disease that may affect host resistance and in case of poor response to conventional mechanical therapy . Locally delivered antibiotics together with mechanical debridement are indicated for non-responding sites of focal infection or in localised recurrent disease . After resolution of the periodontal infection, the patient should be placed on an individually tailored maintenance care programme . Optimal plaque control by the patient is of paramount importance for a favourable clinical and microbiological response to any form of periodontal therapy. Acta Pol Pharm, 2003 Sep-Oct, 60(5), 401 - 4 Non-antibiotics--drugs with additional antimicrobial activity; Tyski S; Antimicrobial activity of antibiotics and chemotherapeutics has been investigated for several years . However, a great variety of pharmaceutical preparations, which are applied in the management of non-infectious diseases have shown also some in vitro antimicrobial activity . These drugs are called "non-antibiotics" . Detected antimicrobial action of non-antibiotics (and non-chemotherapeutics), emphasises a necessity to neutralise this activity during microbial purity examination in the pharmaceutical industry . It is possible that some of these compounds can enhance the activity of certain antibiotics against bacteria or fungi. Cell Mol Life Sci, 2004 Mar, 61(5), 618 - 23 Trichomonas vaginalis degrades nitric oxide and expresses a flavorubredoxin-like protein: a new pathogenic mechanism? Sarti P, Fiori PL, Forte E, Rappelli P, Teixeira M, Mastronicola D, Sanciu G, Giuffre A, Brunori M. Besides possessing many physiological roles, nitric oxide (NO) produced by the immune system in infectious diseases has antimicrobial effects . Trichomoniasis, the most widespread non-viral sexually transmitted disease caused by the microaerophilic protist Trichomonas vaginalis, often evolves into a chronic infection, with the parasite able to survive in the microaerobic, NO-enriched vaginal environment . We relate this property to the finding that T . vaginalis degrades NO under anaerobic conditions, as assessed amperometrically . This activity, which is maximal (133 +/- 41 nmol NO/10(8) cells per minute at 20 degrees C) at low NO concentrations (< or = 1.2 microM), was found to be: (i) NADH dependent, (ii) cyanide insensitive and (iii) inhibited by O(2) . These features are consistent with those of the Escherichia coli A-type flavoprotein (ATF), recently discovered to be endowed with NO reductase activity . Using antibodies against the ATF from E . coli, a protein band was immunodetected in the parasite grown in a standard medium . If confirmed, the expression of an ATF in eukaryotes suggests that the genes coding for ATFs were transferred during evolution from anaerobic Prokarya to pathogenic protists, to increase their fitness for the microaerobic, parasitic life style . Thus the demonstration of an ATF in T . vaginalis would appear relevant to both pathology and evolutionary biology . Interestingly, genomic analysis has recently demonstrated that Giardia intestinalis and other pathogenic protists have genes coding for ATFs. Acta Crystallogr C, 2004 Mar, 60(Pt 3), m126 - 8 Epub 2004 Feb 19. Two new polymorphs of trans-bis(hinokitiolato)copper(II); Arvanitis GM et al.; The title complex {systematic name: trans-bis(3-isopropyl-7-oxocyclohepta-1,3,5-trienolato)copper(II)}, {Cu(C10H11O2)2}, is a substance possessing antimicrobial activity . The compound crystallizes in a number of polymorphic forms, the structures for two of which are reported here . Stacks of square-planar molecules exhibiting weak intermolecular copper-olefin pi interactions (not observed in earlier reports on this substance) are described . The molecules have crystallographically imposed inversion symmetry, with stacking and copper-olefin pi distances ranging from 3.226 (2) to 3.336 (1) A. J Clin Microbiol, 2004 Mar, 42(3), 1048 - 57 Microarray-based identification of bacteria in clinical samples by solid-phase PCR amplification of 23S ribosomal DNA sequences; Mitterer G et al.; The rapid identification of the bacteria in clinical samples is important for patient management and antimicrobial therapy . We describe a DNA microarray-based PCR approach for the quick detection and identification of bacteria from cervical swab specimens from mares . This on-chip PCR method combines the amplification of a variable region of bacterial 23S ribosomal DNA and the simultaneous sequence-specific detection on a solid phase . The solid phase contains bacterial species-specific primers covalently bound to a glass support . During the solid-phase amplification reaction the polymerase elongates perfectly matched primers and incorporates biotin-labeled nucleotides . The reaction products are visualized by streptavidin-cyanine 5 staining, followed by fluorescence scanning . This procedure successfully identified from pure cultures 22 bacteria that are common causes of abortion and sterility in mares . Using the on-chip PCR method, we also tested 21 cervical swab specimens from mares for the presence of pathogenic bacteria and compared the results with those of conventional bacteriological culture methods . Our method correctly identified the bacteria in 12 cervical swab samples, 8 of which contained more than one bacterial species . Due to the higher sensitivity of the on-chip PCR, this method identified bacteria in five cervical swab samples which were not detected by the conventional identification procedure . Our results show that this method will have great potential to be incorporated into the routine microbiology laboratory. Am J Physiol Lung Cell Mol Physiol, 2004 Apr, 286(4), L750 - 5 Secretion of lactoferrin and lysozyme by cultures of human airway epithelium; Dubin RF et al.; Lactoferrin and lysozyme are important antimicrobial compounds of airway surface liquid, derived predominantly from serous cells of submucosal glands but also from surface epithelium . Here we compared release of these compounds from the following human cell cultures: primary cultures of tracheal epithelium (HTE), Calu-3 cells (a lung adenocarcinoma cell line frequently used as a model of serous gland cells), 16HBE14o- cells (an SV40 transformed line from airway surface epithelium), T84 cells (a colon carcinoma cell line), and human foreskin fibroblasts (HFF) . For lysozyme, baseline secretory rates were in the order Calu-3 > 16HBE14o- > HTE T84 > HFF = 0; for lactoferrin, the only cell type showing measurable release was HTE; for mucus, HTE > Calu-3 > 16HBE14o- T84 > HFF = 0 . A wide variety of neurohumoral agents and inflammatory stimuli was without effect on lactoferrin and lysozyme release from HTE or Calu-3 cells, although forskolin did stimulate secretion of water and lysozyme from Calu-3 cells . However, the concentration of lysozyme in the forskolin-induced secretions was much less than in airway gland secretions . Thus our data cast doubt on the utility of Calu-3 cells as a model of airway serous gland cells but do suggest that HTE could prove highly suitable for studies of mucin synthesis and release. J Hosp Infect, 2004 Mar, 56(3), 202 - 7 Evaluation of current practices in surgical antimicrobial prophylaxis in primary total hip prosthesis--a multicentre survey in private and public French hospitals; Quenon JL et al.; Deep wound infection is a rare but dreaded postoperative complication after total hip prosthesis (THP) procedures but its incidence can be reduced by systemic antimicrobial prophylaxis . The objective of the present study was to evaluate whether antimicrobial prophylaxis for elective primary THP in patients without any history of hip infection, in orthopaedic wards, participating on a voluntary basis, in French public hospitals and private institutions, complies with published guidelines . Three types of data were collected from anaesthetic and surgical records (November 2000-January 2001) in participating hospitals: (1) administrative data on the hospitals and orthopaedic wards, (2) data on patients, (3) data on compliance of practices with five critical criteria derived from published French guidelines . These criteria concerned administration of prophylaxis, choice of antimicrobial agent, dose of first injection, timing of administration and total length of prophylaxis . Thirty institutions sent data files on 1257 THPs to the coordination centre . Compliance exceeded 80% for all criteria except one (interval between first and second injection) . Cumulative compliance with the five criteria was 66.9% . Major compliance failures were an inappropriate interval between the first injection and incision, and total antimicrobial prophylaxis exceeding 48 h . Cumulative compliance was 87.9% in teaching hospitals, 61.8% in general hospitals and 67.7% in private institutions (P<1 x 10(-6)) . It was slightly higher when the annual number of interventions was > or =100 (69.4 versus 62.3%; P<0.02) . Although the protocol for antimicrobial prophylaxis in THP was clear and easy, one-third of practices did not conform with all five standards . Knowledge of the results by the participating institutions should encourage them to set up working groups to draft care protocols for THP and other surgical interventions, in order to improve practice and perhaps reduce costs. Peptides, 2004 Jan, 25(1), 29 - 36 Antimicrobial properties of the frog skin peptide, ranatuerin-1 and its {Lys-8}-substituted analog; Sonnevend A et al.; The predicted conformation of ranatuerin-1 (SMLSVLKNLG(10)KVGLGFVACK(20)INK QC), an antimicrobial peptide first isolated from the skin of the bullfrog Rana catesbeiana, comprises three structural domains: alpha-helix (residues 1-8), beta-sheet (residues 11-16) and beta-turn (residues 20-25) . Circular dichroism studies confirm significant alpha-helical character in 50% trifluoroethanol . Replacement of Cys-19 and Cys-25 by serine resulted only in decreased antimicrobial potency but deletion of either the cyclic heptapeptide region {residues (19-25)} or the N-terminal domain {residues (1-8)} produced inactive analogs . Substitution of the glycine residues in the central domain of the {Ser-19, Ser-25} analog by lysine produced inactive peptides despite increased alpha-helical content and cationicity . The substitution Asn-8-->Lys gave a ranatuerin-1 analog with increased alpha-helicity and cationicity and increased potency against a range of Gram-positive and Gram-negative bacteria and against C . albicans but only a small increase (21%) in hemolytic activity . In contrast, increasing alpha-helicity and hydrophobicity by the substitution Asn-22-->Ala resulted in a 3.5-fold increase in hemolytic activity . Effects on antimicrobial potencies of substitutions of neutral amino acids at positions 4, 18, 22, and 24 by lysine were less marked . Strains of pathogenic E . coli from different groups showed varying degrees of sensitivity to ranatuerin-1 (MIC between 5 and 40 microM) but {Lys-8} ranatuerin-1 showed increased potency (between 2- and 8-fold; P < 0.01) against all strains . The data demonstrate that {Lys-8} ranatuerin-1 shows potential as a candidate for drug development. J Clin Periodontol, 2003 Dec, 30(12), 1024 - 30 Effect of triclosan on healing following non-surgical periodontal therapy in smokers; Kerdvongbundit V et al.; BACKGROUND: Tobacco smoking is an established risk factor for periodontitis, and is associated with periodontal attachment and tooth loss . Clinical studies have indicated that smoking may adversely affect and impede healing following periodontal therapy . Adjunctive antimicrobials, on the other hand, have been shown to enhance the effect of non-surgical periodontal therapy . The objective of this study was to evaluate the effect of a triclosan/copolymer/fluoride dentifrice on healing following non-surgical periodontal therapy in smokers . METHODS: Sixty smokers (aged 35-59 years; 23 females) with chronic periodontal disease volunteered to participate in a double-blind, randomized, controlled, clinical trial . The subjects were randomly assigned to use a triclosan/copolymer/fluoride (30 subjects) or a standard fluoride (30 subjects) dentifrice and received detailed information on proper techniques for self-performed plaque control . The participants then received non-surgical periodontal therapy followed by periodontal maintenance care every 6 months over 24 months . Clinical recordings included evaluation of oral hygiene standards, gingival health, and periodontal status . RESULTS: Subjects using the triclosan/copolymer/fluoride dentifrice exhibited significantly improved oral hygiene conditions, gingival health, and periodontal status compared with those using the standard fluoride dentifrice over the 24-month maintenance interval . CONCLUSIONS: The results suggest that an oral hygiene regimen including a triclosan/copolymer/fluoride dentifrice may sustain the short-term effect of non-surgical periodontal therapy in smokers. Science, 2004 Mar 5, 303(5663), 1532 - 5 Neutrophil extracellular traps kill bacteria; Brinkmann V et al.; Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome . Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria . These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria . NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation . NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria. Pathol Biol (Paris), 2004 Mar, 52(2), 76 - 81 {E . coli: resistance to quinolones and beta-lactams of clinical strains isolated in the Franche-Comté region of France}; Talon D et al.; AIM OF THE STUDY: Numerous European studies have reported an increase of resistance to quinolones among E . coli . We conducted a regional study to update our knowledge on this evolution . MATERIALS AND METHODS: We evaluated the resistance phenotype and genotype of 115 clinical strains of E . coli . We collected data on individual treatment with fluoroquinolones, and the evolution of the use of these antimicrobial agents . RESULTS: Resistance to nalidixic acid and ciprofloxacin was 13.0 and 6.9, respectively . The frequency of resistance increased from 1999 to 2001, from 7.5% to 13.0% for nalidixic acid and from 5.4% to 6.9% for fluoroquinolones . Resistance to quinolones was significantly associated to beta-lactams resistance and was slightly higher for nosocomial isolates compared to community-acquired isolates . Previous treatment with fluoroquinolones was the major risk factor associated to E . coli resistance . From 1997 to 2001, fluoroquinolones use has increased in our hospital and particularly in the community . Analysis of molecular epidemiology shows a large clonal diversity among E . coli isolates . CONCLUSION: This study confirms the evolution through resistance to quinolones of E . coli isolates . This observation is not due to dissemination of resistant clonal strains and the selective pressure exerted by fluoroquinolones influences this evolution . Therapeutic alternatives, surveillance, and restriction of fluoroquinolones use are needed to control this spread of resistance. Clin Infect Dis, 2004 Mar 15, 38(6), 799 - 804 Epub 2004 Mar 01. Bordetella holmesii bacteremia: a newly recognized clinical entity among asplenic patients; Shepard CW et al.; Bordetella holmesii is a recently identified gram-negative bacterial species associated with bacteremia, endocarditis, and respiratory illness, mainly in immunocompromised patients . From isolates submitted to the Centers for Disease Control and Prevention from 1983 through 2000 for further identification, we identified 30 patients with B . holmesii bacteremia . Of the 26 patients for whom data were available, 22 (85%) were anatomically or functionally asplenic . In 25 (96%) of the 26 patients, B . holmesii was the only organism isolated from blood samples, and 14 patients (54%) had B . holmesii recovered from > or =2 blood cultures . The clinical course of the infection was generally characterized by a nonspecific febrile illness . Twenty-one patients (81%) were treated with various antimicrobial agents, and 20 (77%) were admitted to the hospital . There were no deaths . Our findings support evidence that B . holmesii may be a true pathogen associated with bacteremia among asplenic patients. Cell Mol Life Sci, 2004 Feb, 61(4), 437 - 55 Antifungal proteins: targets, mechanisms and prospective applications; Theis T et al.; All organisms have evolved several defence systems in order to protect themselves against bacteria, fungi and viruses . Higher organisms have developed a complex network of humoral and cellular responses, called adaptive immunity . A second defence system, innate immunity, was discovered in the early 1980s, consisting of small cationic peptides with a broad antimicrobial spectrum . These proteins act immediately at sites of infection or inflammation . The production of proteins with antimicrobial activity was not limited to higher organisms but was also found in insects, plants and microorganisms . During the last 2 decades a broad range of proteins with very different structural features have been isolated and characterised from differing organisms ranging from bacteria to human beings . Over 500 cationic membrane-acting proteins with antimicrobial and antifungal activities have been identified to date . Apart from these proteins, a very large number of antifungal proteins active on the fungal cell wall, on enzymes of the cell wall synthesis machinery, the plasma membrane and on intracellular targets have been characterised. J Chemother, 2003 Dec, 15(6), 525 - 35 Resistance to beta-lactams--the permutations; Amyes SG; The beta-lactam family of antimicrobials, in particular penicillins and cephalosporins, is the mainstay of treatment for community-acquired infections . However, the emergence of resistant isolates to these agents has raised concerns regarding the continued efficacy of existing therapies . Resistance to beta-lactams is most commonly expressed by the microbial production of beta-lactamases that hydrolyze the beta-lactam ring . Three further resistance mechanisms include conformational changes in penicillin-binding proteins (PBPs); permeability changes in the outer membrane; and active efflux of the antimicrobial . In addition to the pre-requisite efficacy and tolerability profiles, new beta-lactams should address these four resistance mechanisms . Overcoming resistance may be a serendipitous event or arrived at by design . A unique synthetic beta-lactam class, which demonstrates promise in terms of its activity against the range of bacteria responsible for community-acquired infections and its inherent stability to hydrolysis by beta-lactamases, is the penems . This discrete class of hybrid molecules combines properties from the penicillin (penam) and cephalosporin (cephem) beta-lactam classes . Faropenem is an example of a penem with a broad spectrum of activity designed to address these resistance issues. Pharmacoepidemiol Drug Saf, 2004 Feb, 13(2), 105 - 10 Utilization of antimicrobials in Rijeka (Croatia); Vlahovic-Palcevski V et al.; PURPOSE: In this study, the extent and pattern of inpatient and outpatient antimicrobial drug use was investigated in Rijeka, Croatia, and the impact of control measures was evaluated . METHODS: Consumption of antibacterials for the years 2000 and 2001 was monitored using the ATC/DDD methodology . RESULTS: During the investigation period, the antimicrobial utilization at the University Hospital Center (UHC) Rijeka has decreased by 14% . In the outpatient setting of the County of Primorje and Gorski kotar, the antimicrobial utilization was similar during both years . At the UHC Rijeka, not only the amount, but the pattern of antibacterial utilization also has changed in contrast to the outpatient setting where the pattern of antimicrobial prescribing remained the same . CONCLUSIONS: The control measures for antibiotic use that were introduced in the outpatient setting did not influence the prescribing habit of primary care physicians, while the impact of hospital antibiotic use control measures was satisfactory . Further investigation is needed to evaluate the impact of these measures on bacterial resistance patterns. Med Sci (Paris), 2004 Feb, 20(2), 169 - 74 {Infectious features of atherosclerosis}; Wyplosz B et al.; As an inflammatory focus, the atherosclerotic plaque is viewed as a response to aggressions . Suppressing these causal injuries appears as the best means for preventing the disease . Infection is among the clues for answering the etiological challenge of atherosclerosis . Through direct or indirect, and specific or non specific pathways, some candidate viruses or bacteria are suspected to induce or stimulate plaque formation or complications . Yet, none of these working hypotheses has reached the level of proof required for establishing a valid concept . Although submitted to intensive investigations, anti-infectious drugs and antimicrobial vaccinations are still far-sighted expectations in the treatment and prevention of coronary artery disease. Cardiovasc J S Afr, 2004 Jan-Feb, 15(1), 14 - 20 Infective endocarditis: improving the diagnostic yield; Koegelenberg CF et al.; INTRODUCTION: Isolating aetiological agents in patients with infective endocarditis (IE) remains problematical . We postulated that the high local incidence of culture-negative IE resulted from antibiotic exposure prior to blood cultures and that a structured delay in therapy in the subacute presentation would improve the diagnostic yield . AIM: We aimed to prospectively observe the diagnostic approach and give an overview of supplementary laboratory tests . STUDY DESIGN: Patients with suspected IE were enrolled into this analytical observational study and followed up for six months (n = 92) . We compared the diagnostic yield and outcome in cases where antibiotics were withheld for 72 hours, with those cases who received early antimicrobials, despite being deemed safe for delayed therapy . RESULTS: Definitive diagnoses (definite or excluded IE) were made in 92.8% of patients where antibiotics were delayed, compared to 60% of patients who received empirical treatment (p = 0.08) . The mortality rates were 18.4% and 30.0% (p = 0.18) . Twenty-three of 26 patients with definite culture-negative IE received antibiotics during the 48 hours preceding cultures, compared to eight of 21 culture-positive patients (P < 0.001) . Screening for atypical bacteria did not improve the yield . C-reactive protein (CRP) had a sensitivity of 97.0% (negative predictive value 87.5%), whereas a positive rheumatoid factor (RF) had a specificity of 93.8% (positive predictive value 91.7%) . CONCLUSIONS: We observed tendencies towards a greater diagnostic yield and lower mortality where antibiotics were initially withheld . Antibiotic prior to blood cultures were an important cause of culture-negative IE . A normal CRP proved useful in excluding IE; a positive RF strongly favoured IE. J Bacteriol, 2004 Mar, 186(6), 1747 - 57 Phospho-N-acetyl-muramyl-pentapeptide translocase from Escherichia coli: catalytic role of conserved aspartic acid residues; Lloyd AJ et al.; Phospho-N-acetyl-muramyl-pentapeptide translocase (translocase 1) catalyzes the first of a sequence of lipid-linked steps that ultimately assemble the peptidoglycan layer of the bacterial cell wall . This essential enzyme is the target of several natural product antibiotics and has recently been the focus of antimicrobial drug discovery programs . The catalytic mechanism of translocase 1 is believed to proceed via a covalent intermediate formed between phospho-N-acetyl-muramyl-pentapeptide and a nucleophilic amino acid residue . Amino acid sequence alignments of the translocase 1 family and members of the related transmembrane phosphosugar transferase superfamily revealed only three conserved residues that possess nucleophilic side chains: the aspartic acid residues D115, D116, and D267 . Here we report the expression and partial purification of Escherichia coli translocase 1 as a C-terminal hexahistidine (C-His6) fusion protein . Three enzymes with the site-directed mutations D115N, D116N, and D267N were constructed, expressed, and purified as C-His6 fusions . Enzymatic analysis established that all three mutations eliminated translocase 1 activity, and this finding verified the essential role of these residues . By analogy with the structural environment of the double aspartate motif found in prenyl transferases, we propose a model whereby D115 and D116 chelate a magnesium ion that coordinates with the pyrophosphate bridge of the UDP-N-acetyl-muramyl-pentapeptide substrate and in which D267 therefore fulfills the role of the translocase 1 active-site nucleophile. Expert Opin Investig Drugs, 2004 Feb, 13(2), 97 - 106 Cationic antimicrobial peptides - an update; Zhang L et al.; Cationic antimicrobial peptides play a very important role in nature as a first line of defence against attack and damage . However, their application to the clinic has not been very encouraging to date . There are indications that the barriers to their success may now be eroding with companies developing peptides to be more stable, cost effective and targeted to specific indications . These include systemic infectious disease, acne, vaginitis, wound infection and inflammation . In addition, the use of such peptides as modulators of innate immunity in the treatment of infectious disease and inflammation has added a further dimension to the field. Expert Opin Pharmacother, 2004 Feb, 5(2), 229 - 35 Clinical use of antimicrobial pharmacodynamic profiles to optimise treatment outcomes in community-acquired bacterial respiratory tract infections: application to telithromycin; Nicolau DP; Despite the revolutionary introduction of antibiotic therapy in the post-World War II era, primary care physicians continue to struggle with the issue of optimal treatment strategies for bacterial infection and the growing problem of antimicrobial resistance . The aggressive use of potent agents as first-line therapy maximises the potential for successful eradication of bacterial pathogens and slowing of the development of drug-resistant strains . Therapeutic drug monitoring and quantitative assessment of antibacterial potency are not always feasible in daily practice, but the pharmacodynamic profiles of antibacterials - which integrate pharmacokinetic profiles and microbiological properties - can be used to predict clinical success . Telithromycin possesses pharmacodynamic characteristics that make this novel ketolide an optimal choice for the empirical management of community-acquired respiratory tract infections. ANZ J Surg, 2004 Mar, 74(3), 139 - 42 Cytotoxicity of topical antimicrobial agents used in burn wounds in Australasia; Fraser JF et al.; BACKGROUND: Burn sepsis is a leading cause of mortality and morbidity in patients with major burns . The use of topical antimicrobial agents has helped improve the survival of these patients . Silvazine (Sigma Pharmaceuticals, Melbourne, Australia) (1% silver sulphadiazine and 0.2% chlorhexidine digluconate) is used exclusively in Australasia, and there is no published study on its cytotoxicity . This study compared the relative cytotoxicity of Silvazine with 1% silver sulphadiazine (Flamazine (Smith & Nephew Healthcare, Hull, UK)) and a silver-based dressing (Acticoat (Smith & Nephew Healthcare, Hull, UK)) . METHODS: Dressings were applied to the centre of culture plates that were then seeded with keratinocytes at an estimated 25% confluence . The plates were incubated for 72 h and culture medium and dressings then removed . Toluidine blue was added to stain the remaining keratinocytes . Following removal of the dye, the plates were photographed under standard conditions and these digital images were analysed using image analysis software . Data was analysed using Student's t-test . RESULTS: In the present study, Silvazine is the most cytotoxic agent . Seventy-two hour exposure to Silvazine in the present study results in almost no keratinocyte survival at all and a highly statistically significant reduction in cell survival relative to control, Acticoat and Flamazine (P<0.001, P<0.01, P<0.01, respectively) . Flamazine is associated with a statistically significant reduction in cell numbers relative to control (P<0.05), but is much less cytotoxic than Silvazine (P<0.005) . CONCLUSION: In this in-vitro study comparing Acticoat, Silvazine and Flamazine, Silvazine shows an increased cytotoxic effect, relative to control, Flamazine and Acticoat . An in-vivo study is required to determine whether this effect is carried into the clinical setting. J Agric Food Chem, 2004 Mar 10, 52(5), 1132 - 7 In vitro antimicrobial and antioxidant activities of the essential oils and various extracts of Thymus eigii M . Zohary et P.H . Davis; Tepe B et al.; This study was designed to examine the in vitro antimicrobial and antioxidant activities of the essential oil and various extracts obtained from aerial parts of Thymus eigii . The essential oil was particularly found to possess stronger antimicrobial activity, whereas other nonpolar extracts and subfractions showed moderate activity and polar extracts remained almost inactive . GC-MS analysis of the oil resulted in the identification of 39 compounds, representing 93.7% of the oil; thymol (30.6%), carvacrol (26.1%), and p-cymene (13.0%) were the main components . The samples were also subjected to a screening for their possible antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and beta-carotene-linoleic acid assays . In the former case, the polar subfraction of the methanol extract was found to be superior to all extracts tested, only 16.8 microg/mL of which provided 50% inhibition, whereas all extracts, particularly the polar ones, seem to inhibit the oxidation of linoleic acid in the latter case . These data were further supported by total phenolics analysis, indicating that the antioxidative potential of the extracts was closely related to their phenolic constituents. J Agric Food Chem, 2004 Mar 10, 52(5), 1077 - 82 Phytotoxic and antimicrobial activities of catechin derivatives; Veluri R et al.; (+/-)-Catechin is a potent phytotoxin, with the phytotoxicity due entirely to the (-)-catechin enantiomer . (+)-Catechin, but not the (-)-enantiomer, has antibacterial and antifungal activities . Tetramethoxy, pentaacetoxy, and cyclic derivatives of (+/-)-catechin retained phytotoxicity . The results indicate that antioxidant properties of catechins are not a determining factor for phytotoxicity . A similar conclusion was reached for the antimicrobial properties . Centaurea maculosa (spotted knapweed) exudes (+/-)-catechin from its roots, but the flavanol is not re-absorbed and hence the weed is not affected . The much less polar tetramethoxy derivative may, however, be absorbed and hence be able to cause toxicity . Because of the combination of phytotoxicity and antimicrobial activity, (+/-)-catechin could be a useful natural herbicide and antimicrobial. Cell Mol Biol (Noisy-le-grand), 2003, 49 Online Pub, OL387 - 92 Low energy proton irradiation effects on alveolar macrophages from young and aged rats; Tasat DR et al.; A prospective study was undertaken to assess the radiotoxicity of accelerated particles in pulmonary alveolar macrophages (AM) . We evaluated the effects of a single dose (10-75 Gy) of an external low-energy (20 MeV) proton beam on cultured AM oxidative metabolism and phagocytic function . Macrophages are the first line of defense against invading pathogens and are known to generate superoxide anion (O2), nitric oxide (NO), and mediators of antimicrobial and antitumoral defense mechanisms . We obtained AM by bronchoalveolar lavage from young (1-2 month old) and aged (9-12 month old) male Wistar rats . Cell viability, phagocytosis, O2 and NO production in control and proton-irradiated cultured AM were evaluated The effect of proton irradiation on cell viability was dose-dependent The higher doses induced a dramatic decrease in viability in the aged population . Phagocytosis increased 1.3-1.4 fold inboth populations irrespective of the dose delivered . Generation of O2 was always higher in the aged population for all the doses assayed and showed no significant variation from the control values . In the young population a clear increase was observed with doses of 25 and 50 Gy . NO production in AM from young animals rose in a dose-dependent manner . Conversely, proton irradiation did not affect NO production in macrophages from aged animals . The results of this study demonstrate that AM isolated from young and aged rats are functionally different and show a distinct behavior when exposed to proton irradiation . These findings suggest that age may condition response and must be taken into account when accelerated particle-radiotherapy protocols are considered as a valid therapeutic option for the treatment of cancer . To the best of our knowledge, this is the first report comparing sham-irradiated and proton-irradiated young and aged AM. Infect Control Hosp Epidemiol, 2004 Feb, 25(2), 173 - 6 Facility-level correlates of antimicrobial use in nursing homes; Loeb M et al.; We assessed the contribution of facility-level variables to antimicrobial use in a cohort of 50 nursing homes and found that antimicrobial use was significantly correlated with the percentage of nursing home residents with feeding tubes, the number of healthcare aides, and the country of origin of the facility. Ann Otol Rhinol Laryngol, 2004 Feb, 113(2), 142 - 6 Sinus tissue concentration of moxifloxacin after a single oral dose; Dinis PB et al.; Moxifloxacin is a new fluoroquinolone antimicrobial approved for the treatment of acute bacterial rhinosinusitis . In order to assess its distribution pattern into the paranasal sinuses, and specifically to evaluate how the histopathologic changes associated with chronic inflammation affect its tissue penetration, we conducted the present investigation, a randomized, open-label, single dose, sinus-tissue pharmacokinetic study with oral moxifloxacin . Twenty adult subjects, selected for surgery because of recalcitrant chronic rhinosinusitis, were preoperatively randomly allocated to receive a tablet of 400 mg moxifloxacin 3 or 4 hours before the procedure . During the operation, tissue samples were collected at specific sinonasal sites, and the concentration levels of the antimicrobial in the different parts of the paranasal sinuses were assayed . Simultaneously, the degree of inflammation at each site was evaluated . We found that moxifloxacin was distributed extensively throughout the sinuses, in both inflamed and noninflamed mucosae, but tended to be concentrated in maxillary sinus cysts . The tissue-to-blood ratios exceeded 4:1 at most sites, with mucosal concentration levels well above the MIC90 values of the drug against a wide range of microorganisms . We concluded that the oral moxifloxacin tissue kinetics provides an extremely potent antimicrobial activity in all parts of the sinuses, regardless of the inflammatory status of the mucosa. Nephrol Dial Transplant, 2004 Jun, 19(6), 1546 - 51 Epub 2004 Feb 19. Prevention of dialysis catheter-related sepsis with a citrate-taurolidine-containing lock solution; Betjes MG et al.; BACKGROUND: The use of haemodialysis catheters is complicated by catheter-related sepsis . Intraluminal colonization of the catheter with bacteria is important in the pathogenesis of catheter-related sepsis . The use of a catheter lock solution containing the antimicrobial taurolidine might prevent bacterial colonization, thereby reducing the incidence of catheter-related sepsis . METHODS: In a randomized prospective trial, patients receiving a dialysis catheter were included and catheters were locked with either heparin or a citrate-taurolidine-containing solution . Blood cultures drawn from the catheter lumen were routinely taken every 2 weeks and at time of removal of the catheter to detect bacterial colonization . Catheter-related sepsis and exit-site infections were registered for both groups . RESULTS: A total of 76 catheters were inserted in 58 patients . The incidence of catheter colonization progressed slowly over time with no differences between dialysis catheters filled with heparin or citrate-taurolidine-containing solution . The number of exit-site infections was also similar between both groups . In the heparin group, four cases of catheter-related sepsis occurred as opposed to no sepsis episodes in the patients with catheters locked with the citrate-taurolidine-containing solution (P<0.5) . No side effects with the use of citrate-taurolidine catheter lock solution were noted . CONCLUSIONS: This study shows that catheter filling with a solution containing the antimicrobial taurolidine may significantly reduce the incidence of catheter-related sepsis . Taurolidine appears to be effective and safe and does not carry the risk for side effects that have been reported for other antimicrobial lock solutions containing gentamicin or high concentrations of citrate. Biomed Pharmacother, 2004 Mar, 58(2), 84 - 9 Influence of alcohol on antimicrobial immunity; Pavia CS et al.; Prolonged consumption of excessive amounts of alcohol by itself, as well as possibly leading to a state of alcoholism, has been a long-standing biological/social problem . As a major public health concern, there is an estimated expenditure of about 20% of total health care costs for medical/hospital care related to alcohol-induced illness . In addition, a significant proportion of both men and women who are hospitalized can be classified as alcoholics . This review focuses primarily on one of the many biomedical problems attributed to alcohol abuse--its adverse effects on our immune-defense system . A considerable body of evidence has mounted, over the past several decades, indicating that those who abuse alcohol are more susceptible to certain infectious disorders and are more prone to bacteremia . Such infections tend to be continuous and are often associated with a high rate of mortality . Also, along these lines, various and suitable animal models have been developed to further elucidate what the causes are for the greater frequency and severity of infectious illnesses, and this review deals primarily with those studies linking alcohol abuse to disruption in the normal functioning of the host's immune surveillance system . Based on the results from both clinical and experimental studies, it would seem that exposure to high levels of alcohol causes decreased humoral and cellular immune responses, thereby seriously limiting our ability to be protected from certain infectious agents. Clin Cornerstone, 2003, Suppl 3, S21 - 8 A new dosing paradigm: high-dose, short-course fluoroquinolone therapy for community-acquired pneumonia; File TM Jr; The goals of optimal antimicrobial therapy are to treat infection effectively, to improve the clinical condition of the patient, and to prevent the emergence of resistant bacterial strains . For ideal drug usage the World Health Organization recommends administering the correct drug by the best route, in the right amount, at optimum intervals for the appropriate period, and after an accurate diagnosis . This article discusses the use of high-dose, short-course fluoroquinolone therapy as an effective option for patients with community-acquired pneumonia. J Infect Chemother, 2004 Feb, 10(1), 49 - 52 A patient with a Mycobacterium avium complex infection complicated by systemic lupus erythematosus; Takada K et al.; A 41-year-old woman was admitted to our hospital because of fever and polyarthralgia . A diagnosis of systemic lupus erythematosus (SLE) was made based on the findings of polyarthritis, leukocytopenia, lymphocytopenia, proteinuria, and positive reactions for antinuclear antibody (ANA) and anti-double strand (ds)DNA antibody . She had also been suffering from a pulmonary Mycobacterium avium complex (MAC) infection with such symptoms as cough and sputum for the past 3 years . Antimicrobial drugs for MAC infection were administered first, and later she was given cyclophosphamide pulse therapy, consisting of methylprednisolone (8 mg/day) and mizoribine (100 mg/day) . Owing to these therapeutic regimens, SLE was successfully treated without an exacerbation of the MAC infection . The risk factors for MAC infection and SLE are also discussed. J Biol Chem, 2004 May 7, 279(19), 19902 - 7 Epub 2004 Feb 27. Paneth cell cryptdins act in vitro as apical paracrine regulators of the innate inflammatory response; Lin PW et al.; Intestinal-specific antimicrobial alpha-defensins, termed cryptdins, are secreted into the intestinal lumen by mouse Paneth cells in response to microbial pathogens . Cryptdins kill microbes by forming pores in their limiting membranes . The cryptdin isoforms 2 and 3 also can form anion-conductive pores in eukaryotic cell membranes, thus affecting cell physiology . Here, we find that when applied to apical membranes of the human intestinal cell line T84, cryptdin 3 (Cr3) induces secretion of the proinflammatory cytokine interleukin 8 (IL-8) in a dose-dependent manner . The induction of IL-8 secretion is specific to the cryptdins that form channels in mammalian cell membranes because cryptdin 4, which does not form pores in T84 cells, does not induce IL-8 secretion . Cr3 induces inflammatory cytokine secretion by activating NF-kappaB and p38 mitogen-activated protein kinase in a Ca2+-dependent manner, but influx by extra-cellular Ca2+ is not involved . Unlike other known inflammatory agonists, signal transduction by Cr3 occurs slowly, suggesting a novel mechanism of action . These results show that selective cryptdins may amplify their roles in innate immunity by acting as novel paracrine agonists to coordinate an inflammatory response with the antimicrobial secretions of Paneth cells. Zhonghua Nei Ke Za Zhi, 2004 Jan, 43(1), 13 - 5 {Effect of CYP2C19 genetic polymorphism on treatment efficacy of Helicobacter pylori infection with rabeprazole-based triple therapy in Chinese}; He XX et al.; OBJECTIVE: To investigate the effect of different S-mephenytoin 4'-hydroxylase (CYP2C19) genotype on the eradication rate of Helicobacter pylori (Hp) by different rabeprazole-based triple therapy in Chinese . METHODS: 128 subjects with Hp positive gastritis or peptic ulcers were randomly assigned to receive 10 mg rabeprazole twice daily with 1000 mg amoxicillin twice daily and 500 mg clarithromycin (RAC group) or 400 mg metronidazole (RAM group) twice daily for 1 week . The CYP2C19 genotype (homozygous extensive metabolizer, hom-Ems; heterozygous extensive metabolizer, het-Ems; or poor metabolizer, PMs) was determined by the polymerase chain reaction-restriction fragment length polymorphism method . More than 4 weeks after completion of treatment, Hp status was assessed by (13)C-urea breath test . RESULTS: The hom-Ems, het-Ems and PMs were 30.5%, 50.0% and 19.5% in 128 subjects, respectively . The eradication rates in the rabeprazole-amoxicillin-clarithromycin (RAC) for clarithromycin-sensitive strains and rabeprazole-amoxicillin-metronidazole (RAM) for metronidazole-sensitive strains groups were 98.1% and 91.3%, respectively, on a per protocol basis . It decreased significantly eradication rates of Hp because the prevalence of primary antimicrobial resistance was 66.8% for metronidazole . When the statistical significance of each parameter associated with treatment outcome was assessed with logistic regression analysis, CYP2C19 genetic polymorphism did not show significant effect on the efficacy of anti-Hp therapy with rabeprazole-based triple regimens . CONCLUSIONS: The efficacy of rabeprazole-based triple regimens is less affected by the CYP2C19 genotype, the RAC regimen can be considered in Chinese. Respirology, 2004 Mar, 9(S1), S38 - S39 Treatment other than by antimicrobial therapy; Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised et al.; Division of Pneumology, University Hospitals, Petersgraben 4, CH-4031 Basel, SwitzerlandBACKGROUND: Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease . Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections . We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay . METHODS: 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124) . On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively . Re-evaluation was possible after 6-24 h in both groups . Primary endpoint was use of antibiotics and analysis was by intention to treat . FINDINGS: Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%) . Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%) . Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%) . In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group . Antibiotic use was significantly reduced in all diagnostic subgroups . Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%) . INTERPRETATION: Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections . Withholding antimicrobial treatment did not compromise outcome . In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications. Eur J Med Chem, 2004 Feb, 39(2), 113 - 22 New alpha-(N)-heterocyclichydrazones: evaluation of anticancer, anti-HIV and antimicrobial activity; Savini L et al.; A series of 3- and 5-methylthiophene-2-carboxaldehyde alpha-(N)-heterocyclichydrazones were synthesized and submitted to an in vitro investigation of their anticancer, anti-HIV and antimicrobial activities . Some of the newly synthesized compounds were found to possess antiproliferative properties, whereas no anti-HIV activity was seen; the most active of the series was the derivative 2i, which exhibited tumour growth inhibition activity against all cell lines displaying GI50 values between 1.63 and 26.5 microM . The title compounds were generally ineffective against Gram-positive and Gram-negative bacteria, while showed a moderate antifungal activity against C . albicans and A . fumigatus. Anal Chem, 2004 Mar 1, 76(5), 1228 - 35 Intramolecular isobaric fragmentation: a curiosity of accurate mass analysis of sulfadimethoxine in pond water; Thurman EM et al.; Liquid chromatography with time-of-flight mass spectrometry (TOF-MS) and quadrupole-time-of-flight (Q-TOF) mass spectrometry/mass spectrometry (MS/MS) were used for the accurate mass analysis of sulfadimethoxine in pond water of a fish hatchery . Sulfadimethoxine is the most important sulfa antimicrobial used in aquaculture to treat bacterial disease in a wide variety of fish . Because correct identification is essential to environmental monitoring of antimicrobial pharmaceuticals, accurate mass analyses (TOF and Q-TOF-MS/MS) were compared to nominal mass measurement (quadrupole ion trap) . It was known that all six members of the sulfa antimicrobial family gave a common 6-sulfanilamido ion at a nominal mass of m/z 156; thus, this ion was the focus of TOF confirmation (exact mass 156.0119 u) along with the protonated molecule (exact mass 311.0814 u) . In the process of accurate mass confirmation of the 156 m/z fragment ion, a second isobaric ion (exact mass m/z 156.0773), was discovered at the same nominal mass, which was not differentiated by quadrupole ion trap . The structure was assigned as 2-4-dimethoxypyridine and is exactly the other protonated half of the sulfadimethoxine molecule . This discovery led to the subsequent use of Q-TOF-MS/MS and high-resolution identification of five other important ion fragments for the identification of sulfadimethoxine in pond water at environmental concentrations . The caveats of using low-resolution mass spectrometry without MS/MS for environmental monitoring are discussed in the light of high profile monitoring of sulfa antimicrobial pharmaceuticals in the aquatic environment. J Nat Prod, 2004 Feb, 67(2), 300 - 10 Biologically active compounds from Aphyllophorales (polypore) fungi; Zjawiony JK; This review describes biologically active natural products isolated from Aphyllophorales, many of which are known as polypores . Polypores are a large group of terrestrial fungi of the phylum Basdiomycota (basidiomycetes), and they along with certain Ascomycota are a major source of pharmacologically active substances . There are about 25 000 species of basidiomycetes, of which about 500 are members of the Aphyllophorales, a polyphyletic group that contains the polypores . Many of these fungi have circumboreal distributions in North America, Europe, and Asia and broad distributions on all inhabited continents and Africa; only a small number of the most common species with the most obvious fruiting bodies (basidiocarps) have been evaluated for biological activity . An estimated 75% of polypore fungi that have been tested show strong antimicrobial activity, and these may constitute a good source for developing new antibiotics . Numerous compounds from these fungi also display antiviral, cytotoxic, and/or antineoplastic activities . Additional important components of this vast arsenal of compounds are polysaccharides derived from the fungal cell walls . These compounds have attracted significant attention in recent years because of their immunomodulatory activities, resulting in antitumor effects . These high molecular weight compounds, often called biological response modifiers (BRM), or immunopotentiators, prevent carcinogenesis, show direct anticancer effects, and prevent tumor metastasis . Some of the protein-bound polysaccharides from polypores and other basidiomycetes have found their way to the market in Japan as anticancer drugs . Finally, numerous compounds with cardiovascular, phytotoxic, immunomodulatory, analgesic, antidiabetic, antioxidant, insecticidal, and nematocidal activities, isolated from polypores, are also presented . In fact many of the fungi mentioned in this paper have long been used in herbal medicine, including polypores such as Ganoderma lucidum (Reishi or Ling Zhi), Laetiporus sulphureus (Chicken-of-the-Woods), Trametes versicolor (Yun Zhi), Grifola umbellata (Zhu Lin), Inonotus obliquus (Chaga), and Wolfiporia cocos (Hoelen). Ear Nose Throat J, 2004 Jan, 83(1 Suppl), 9 - 11 The evolution of ototopical therapy: from cumin to quinolones; Myer CM 3rd; A radical change has occurred in the management of otorrhea over the past decade . Multiple studies have supported the efficacy of topical quinolones in the management of acute otitis media, acute otitis externa, and CSOM . For the first time, otolaryngologists have a scientific foundation on which to base our treatment protocols for these conditions . We no longer must rely solely on our clinical experience and prejudices . The quinolone drops have a superior safety profile and a broad antimicrobial spectrum, their overall cost is lower than the alternatives, and their convenient dosing schedule is tolerated well by most patients . When one takes all these factors into consideration, it becomes clear that topical quinolone therapy, with or without a steroid additive, is the treatment of choice for otorrhea in patients with a tympanic membrane perforation or ventilating tube . The development of ototopical medications has followed along the lines of Darwinian evolution, and the quinolone drops have clearly demonstrated the concept of "survival of the fittest." Clin Infect Dis, 2004 Mar 1, 38(5), 663 - 9 Epub 2004 Feb 17. Gentamicin and tetracyclines for the treatment of human plague: review of 75 cases in new Mexico, 1985-1999; Boulanger LL et al.; Streptomycin, an antimicrobial with limited availability, is the treatment of choice for plague, a fulminating and potentially epidemic disease that poses a bioterrorism concern . We evaluated the efficacy of gentamicin and tetracyclines for treating human plague . A medical record review was conducted on all 75 patients with plague who were reported in New Mexico during 1985-1999 . Fifty patients were included in an analysis that compared streptomycin-treated patients (n=14) with those treated with gentamicin and/or a tetracycline (n=36) . The mean numbers of fever days, hospital days, and complications and the number of deaths did not differ between patients treated with streptomycin and those treated with gentamicin . One patient who received tetracycline alone experienced a serious complication . Gentamicin alone or in combination with a tetracycline was as efficacious as streptomycin for treating human plague . The efficacy of a tetracycline alone could not be determined from the study. Eur J Clin Microbiol Infect Dis, 2004 Mar, 23(3), 203 - 4 Epub 2004 Feb 19. Severe Mycoplasma hominis infections in two renal transplant patients; Rohner P et al.; Systemic infections due to Mycoplasma hominis are rare and occur mainly in immunocompromised patients . Reported here are the cases of two renal transplant patients with peritonitis who did not respond to empirical antimicrobial treatment . Effective treatment with doxycycline was administered only after definitive identification of Mycoplasma hominis was achieved . For this identification, the new genetic amplification-sequencing method was invaluable. Pediatr Nephrol, 2004 Apr, 19(4), 445 - 7 Epub 2004 Feb 21. Cefepime-induced non-convulsive status epilepticus in a peritoneal dialysis patient; Alpay H et al.; Non-convulsive status epilepticus related to cefepime has not been reported in childhood dialysis patients, although several adult cases have been reported . We report a state of acute confusion in a 15-year-old boy on continuous ambulatory peritoneal dialysis (CAPD) receiving cefepime that was diagnosed as status epilepticus by electroencephalography (EEG) . The EEG improved after anticonvulsive therapy . All clinical symptoms disappeared dramatically within 24 h of discontinuation of cefepime . The differential diagnosis of confusional states and the mechanisms of the convulsive effects of antimicrobials in chronic renal failure are discussed . The importance that the clinician is aware of the rare side effects of antimicrobials is emphasized. J Intensive Care Med, 2003 Nov-Dec, 18(6), 295 - 312 Management of infectious complications in the hematopoietic stem cell transplant recipient; Nichols WG; Despite impressive accomplishments in supportive care over the past decade, infections with a diverse group of microorganisms remain leading causes of morbidity and mortality after hematopoietic stem cell transplantation . The epidemiology of infectious complications has shifted substantially in the past decade with changes in antimicrobial prophylaxis, conditioning regimens, and graft manipulation, such that invasive mould infections and late viral infections are now the overriding concerns . Individual patient risk for infections is predicated on multiple disease-specific, patient-specific, and transplant-related factors but often tracks with the cumulative level of immunosuppression (such as dose of corticosteroids used for the treatment of graft vs host disease {GVHD}) . New antivirals and antifungals have entered clinical practice and hold considerable promise for improved outcomes. Aliment Pharmacol Ther, 2004 Feb 1, 19(3), 349 - 58 Economic evaluation of Helicobacter pylori eradication in the CADET-Hp randomized controlled trial of H . pylori-positive primary care patients with uninvestigated dyspepsia; Chiba N et al.; BACKGROUND: Adult Helicobacter pylori-positive patients by 13C-urea breath test with uninvestigated dyspepsia symptoms were randomized to 1-week eradication treatment with omeprazole, metronidazole and clarithromycin (OMC) vs . omeprazole and placebo antimicrobials (OPP) in the Canadian Adult Dyspepsia Empiric Treatment-H . pylori-positive (CADET-Hp) study . AIM: To perform an economic evaluation of this 1-year study . METHODS: Following blind eradication treatment, family practitioners managed patients according to their usual practices . Health resource utilization information was collected prospectively . From the mean costs of the health resources consumed and the treatment outcomes, the incremental cost-effectiveness ratios and incremental net benefits of eradication treatment vs . OPP were determined . RESULTS: Eradication therapy significantly improved dyspepsia symptoms (treatment success: OMC, 50%; OPP, 36%; P = 0.02) . The incremental cost-effectiveness ratio of OMC vs . OPP was - 387 Canadian dollars (CAD$) per treatment success (90% CI, - CAD$1707, CAD$607), indicating a lower cost with treatment success . The incremental net benefit analysis showed that H . pylori eradication was cost-effective if the willingness-to-pay value exceeded a nominal figure of CAD$100 from a health service perspective or CAD$607 from the societal perspective . CONCLUSION: In uninvestigated patients presenting with dyspepsia at the primary care level, eradication of H . pylori in those who are H . pylori positive leads to a cost-effective improvement in dyspepsia symptoms compared with a strategy of not eradicating H . pylori in these patients. Sci STKE . 2004 Feb 17;2004(221):pe6. The role of membrane-bound ankyrin-repeat protein ACD6 in programmed cell death and plant defense; Dong X; Programmed cell death (PCD) is a common defense response in plants against pathogen infection . The recently cloned ACD6 gene was identified in an Arabidopsis mutant, accelerated cell death 6 (acd6), that undergoes PCD in the absence of a pathogen challenge . ACD6 is a founding member of a large family of genes that encode proteins with a short amino-terminal region, nine ankyrin repeats in the middle, and five putative transmembrane domains in the carboxyl-terminal region . Characterization of the original gain-of-function acd6 mutant and a transferred-DNA knockout mutant acd6-T showed that ACD6 is an activator of the defense pathway against bacterial pathogens and plays a role in PCD through regulation of the defense signal salicylic acid (SA) . SA mediates not only downstream pathogenesis-related (PR) genes, which encode proteins with antimicrobial activities, but also ACD6, forming a feedback signal amplification loop. Antimicrob Agents Chemother, 2004 Mar, 48(3), 1037 - 9 In vitro activities of new quinolones and oxazolidinones against Actinomadura madurae; Vera-Cabrera L et al.; In this work, we studied the in vitro sensitivity of 24 strains of Actinomadura madurae to a new oxazolidinone (DA-7867), gatifloxacin, moxifloxacin, and garenoxacin by using a broth microdilution method . We observed that the A . madurae strains had a high level of sensitivity to all the antimicrobials tested . The most active drug was DA-7867, with a MIC at which 90% of the strains are inhibited (MIC(90)) of 0.125 micro g/ml and a MIC(50) of 0.06 micro g/ml. Antimicrob Agents Chemother, 2004 Mar, 48(3), 1012 - 6 In vitro activities of moxifloxacin against 900 aerobic and anaerobic surgical isolates from patients with intra-abdominal and diabetic foot infections; Edmiston CE et al.; The in vitro activities of moxifloxacin, ciprofloxacin, levofloxacin, gatifloxacin, imipenem, piperacillin-tazobactam, clindamycin, and metronidazole against 900 surgical isolates were determined using NCCLS testing methods . Moxifloxacin exhibited good to excellent antimicrobial activity against most aerobic (90.8%) and anaerobic (97.1%) microorganisms, suggesting that it may be effective for the treatment of polymicrobial surgical infections. Antimicrob Agents Chemother, 2004 Mar, 48(3), 924 - 9 Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages; Mamani-Matsuda M et al.; In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-alpha and nitric oxide derivatives . In the present study, quercetin (3,3',4',5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability . Quercetin directly promoted T . b . gambiense death by apoptosis as shown by Annexin V binding . In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-alpha and nitric oxide produced by activated human macrophages . These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis. Antimicrob Agents Chemother, 2004 Mar, 48(3), 832 - 7 In vitro and in vivo activities of antimicrobials against Nocardia brasiliensis; Gomez-Flores A et al.; In Mexico mycetomas are mostly produced by Nocardia brasiliensis, which can be isolated from about 86% of cases . In the present work, we determined the sensitivities of 30 N . brasiliensis strains isolated from patients with mycetoma to several groups of antimicrobials . As a first screening step we carried out disk diffusion assays with 44 antimicrobials, including aminoglycosides, cephalosporins, penicillins, quinolones, macrolides, and some others . In these assays we observed that some antimicrobials have an effect on more than 66% of the strains: linezolid, amikacin, gentamicin, isepamicin, netilmicin, tobramycin, minocycline, amoxicillin-clavulanic acid, piperacillin-tazobactam, nitroxolin, and spiramycin . Drug activity was confirmed quantitatively by the broth microdilution method . Amoxicillin-clavulanic acid, linezolid, and amikacin, which have been used to treat patients, were tested in an experimental model of mycetoma in BALB/c mice in order to validate the in vitro results . Linezolid showed the highest activity in vivo, followed by the combination amoxicillin-clavulanic acid and amikacin. Antimicrob Agents Chemother, 2004 Mar, 48(3), 728 - 38 Mechanism of action of the mannopeptimycins, a novel class of glycopeptide antibiotics active against vancomycin-resistant gram-positive bacteria; Ruzin A et al.; The naturally occurring mannopeptimycins (formerly AC98-1 through AC98-5) are a novel class of glycopeptide antibiotics that are active against a wide variety of gram-positive bacteria . The structures of the mannopeptimycins suggested that they might act by targeting cell wall biosynthesis, similar to other known glycopeptide antibiotics; but the fact that the mannopeptimycins retain activity against vancomycin-resistant organisms suggested that they might have a unique mode of action . By using a radioactive mannopeptimycin derivative bearing a photoactivation ligand, it was shown that mannopeptimycins interact with the membrane-bound cell wall precursor lipid II {C(55)-MurNAc-(peptide)-GlcNAc} and that this interaction is different from the binding of other lipid II-binding antibiotics such as vancomycin and mersacidin . The antimicrobial activities of several mannopeptimycin derivatives correlated with their affinities toward lipid II, suggesting that the inhibition of cell wall biosynthesis was primarily through lipid II binding . In addition, it was shown that mannopeptimycins bind to lipoteichoic acid in a rather nonspecific interaction, which might facilitate the accumulation of antibiotic on the bacterial cell surface. Vet Ophthalmol, 2004 Mar-Apr, 7(2), 71 - 7 The tear film and ocular mucins; Davidson HJ et al.; Abstract The trilaminar tear film, composed of the lipid, aqueous and mucin layers, has many functions including defending the ocular surface . The aqueous layer has several soluble antimicrobial factors that protect the ocular surface . Ocular mucins have recently been studied with regard to their role in the defense of the eye as well as in dry eye syndromes . To date, 15 mucin genes have been identified, and six of these mucin genes are localized to or secreted by ocular glands or epithelia . Understanding the production, secretion and function of ocular mucins will aid in the treatment of dry eye syndromes and ocular surface microbial infections. Sichuan Da Xue Xue Bao Yi Xue Ban, 2004 Jan, 35(1), 91 - 3 {Surveillance on antibiotic resistance of Stenotrophomonas maltophilia in Chengdu and Chongqing area}; Tao CM et al.; OBJECTIVE: To survey the antibiotic resistance of Stenotrophomonas maltophilia in Chengdu and Chongqing area and guide the rational antibiotics usage in the treatment of Stenotrophomonas maltophilia infection . METHODS: Minimal inhibitory concentrations (MICs) of 9 antibiotics against Stenotrophomonas maltophilia were measured using two-fold agar dilution method . RESULTS: A total of 154 strains of Stenotrophomonas maltophilia are multi-drug resistant . But the resistant ratios of trimethoprim-sulfamethoxazole, ticarcillin-clavavulanic acid and fluoroquinolones are lower; especially, new fluoroquinolones have stronger antimicrobial activities . CONCLUSION: The rate of isolating Stenotrophomonas maltophilia strains from clinical samples has been rising . In the therapy of Stenotrophomonas maltophilia infection, trimethoprim-sulfamethoxazole or fluoroquinolones is empirically the medicine of choice . For the treatment of serious infection, the administration of trimethoprim-sulfamethoxazole combined with ticarcillin-clavavulanic acid or new fluoroquinolones is rational. Breast Cancer Res, 2004, 6(2), R92 - 109 Epub 2003 Dec 18. Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression; Clarkson RW et al.; INTRODUCTION: In order to gain a better understanding of the molecular processes that underlie apoptosis and tissue regression in mammary gland, we undertook a large-scale analysis of transcriptional changes during the mouse mammary pregnancy cycle, with emphasis on the transition from lactation to involution . METHOD: Affymetrix microarrays, representing 8618 genes, were used to compare mammary tissue from 12 time points (one virgin, three gestation, three lactation and five involution stages) . Six animals were used for each time point . Common patterns of gene expression across all time points were identified and related to biological function . RESULTS: The majority of significantly induced genes in involution were also differentially regulated at earlier stages in the pregnancy cycle . This included a marked increase in inflammatory mediators during involution and at parturition, which correlated with leukaemia inhibitory factor-Stat3 (signal transducer and activator of signalling-3) signalling . Before involution, expected increases in cell proliferation, biosynthesis and metabolism-related genes were observed . During involution, the first 24 hours after weaning was characterized by a transient increase in expression of components of the death receptor pathways of apoptosis, inflammatory cytokines and acute phase response genes . After 24 hours, regulators of intrinsic apoptosis were induced in conjunction with markers of phagocyte activity, matrix proteases, suppressors of neutrophils and soluble components of specific and innate immunity . CONCLUSION: We provide a resource of mouse mammary gene expression data for download or online analysis . Here we highlight the sequential induction of distinct apoptosis pathways in involution and the stimulation of immunomodulatory signals, which probably suppress the potentially damaging effects of a cellular inflammatory response while maintaining an appropriate antimicrobial and phagocytic environment. Headache, 2004 Jan, 44(1), 75 - 8 Pituitary apoplexy masquerading as meningoencephalitis; Jassal DS et al.; BACKGROUND: Pituitary apoplexy, a rare but life-threatening disorder, is characterized by the abrupt destruction of pituitary tissue secondary to infarction or hemorrhage of the gland itself . Its clinical features include severe headache, stiff neck, fever, visual disturbances, and symptoms of hypoadrenalism . OBJECTIVES: To assess how pituitary apoplexy may mimic the clinical findings of an infectious meningoencephalitis . METHODS AND RESULTS: We describe 3 individuals whose clinical profile and paraclinical studies were consistent with a diagnosis of presumed infectious meningoencephalitis . With minimal improvement on antimicrobial therapy, however, an extensive clinical and radiographic reevaluation yielded pituitary apoplexy as the etiology of their acute neurologic event . CONCLUSIONS: Pituitary apoplexy is often misdiagnosed as meningitis or subarachnoid hemorrhage due to the presence of leukocytes and erythrocytes in the cerebrospinal fluid . These cases serve to highlight the importance of maintaining a broad differential diagnosis when evaluating patients presenting with an acute headache. Eur Respir J, 2004 Feb, 23(2), 327 - 33 Innate immunity in the lung: how epithelial cells fight against respiratory pathogens; Bals R et al.; The human lung is exposed to a large number of airborne pathogens as a result of the daily inhalation of 10,000 litres of air . The observation that respiratory infections are nevertheless rare is testimony to the presence of an efficient host defence system at the mucosal surface of the lung . The airway epithelium is strategically positioned at the interface with the environment, and thus plays a key role in this host defence system . Recognition systems employed by airway epithelial cells to respond to microbial exposure include the action of the toll-like receptors . The airway epithelium responds to such exposure by increasing its production of mediators such as cytokines, chemokines and antimicrobial peptides . Recent findings indicate the importance of these peptides as effector molecules of innate immunity by killing microorganisms, but also as regulators of inflammation, immunity and wound repair . Finally, the clinical relevance of the functions of the airway epithelium in innate immunity is discussed. Int J Hematol, 2004 Jan, 79(1), 85 - 91 Hemopoietic recovery and infectious complications in breast cancer and multiple myeloma after autologous CD34+ cell-selected peripheral blood progenitor cell transplantation; De Rosa L et al.; Autografting with CD34+ cell-selected peripheral blood progenitor cells (PBPC) is often associated with a prolonged recovery time and a higher incidence of infections . The aim of our study was to evaluate whether underlying disease influences hemopoietic recovery and the infectious complications occurring after transplantation . We studied 19 breast cancer (BC) patients and 17 multiple myeloma (MM) patients entered in a high-dose chemotherapy (HDC) program of tandem autografting with CD34+ cell-selected PBPC . PBPC were collected after mobilizing chemotherapy plus granulocyte colony-stimulating factor and were processed for selection of CD34+ cells . After selection, a median of 53% CD34+ cells was recovered with a median final purity of 92% with no significant differences between the MM (52% and 92%, respectively) and BC (53% and 89%, respectively) patients . Medians of 4.5 x 10(6)/kg CD34+ cells (BC, 4.4 x 10(6)/kg; MM, 5.4 x 10(6)/kg) and 18 x 10(4)/kg colony-forming units-granulocyte-macrophage (BC, 21 x 10(4)/kg: MM, 16 x 10(4)/kg) were reinfused after each HDC . Twenty-six patients (10 MM and 16 BC) underwent tandem autografting, and 10 patients received only 1 autograft because of inadequate collection (5 patients), clinical condition (3 patients), and refusal (2 patients) . In the BC patients, the HDC regimen included a high-dose melphalan course followed by an ICE (ifosfamide, carboplatin, and etoposide) course . In the MM patients, the regimen consisted of a course of high-dose melphalan therapy and a course of ICBV (idarubicin, cyclophosphamide {Cytoxan}, BCNU, and etoposide) or total body irradiation, etoposide, and Cytoxan . We found a significantly prolonged time for neutrophil recovery to > 500/microL in the MM patients (13 days versus 10 days; P < .002), whereas the times for platelet recovery to > 20,000/microL in the two groups were not different (13 days versus 12 days; not significant) . No late engraftment failures and no toxic deaths were observed . The incidences of extrahematologic toxicity were similar for the two patient groups . All patients received similar anti-infection prophylaxis for 3 months after transplantation . After 12 months of observation, we found a statistically significant higher incidence of bacterial infections in MM patients in both the early (77.8% versus 48.6%; P < .034) and the late (41.1% versus 0%; P < .014) posttransplantation periods, whereas the incidences of fungal infections were similar in the two groups . Viral infections consisted of herpes zoster virus infection in 2 patients of each group, and cytomegalovirus infection was observed in 3 MM patients and no BC patients . Our experience demonstrates a prolonged neutrophil recovery time and higher incidences of bacterial and viral infections in MM patients compared with BC patients . These observations, although limited by the small sample size, suggest that the underlying disease may influence the incidence of infections after CD34- cell-selected transplantation and should be considered in the planning of appropriate antimicrobial prophylaxis in the autologous transplantation setting. Vet Rec, 2004 Jan 31, 154(5), 136 - 40 Use of antimicrobial drugs in Swedish dairy calves and replacement heifers; Ortman K et al.; A total of 3081 heifer calves in 122 Swedish dairy herds were monitored from birth to first calving, and all their diseases and treatments were recorded . There were 1268 cases of infectious diseases, of which 335 (26.4 per cent) were treated with antimicrobial drugs . Just over 90 per cent of the treatments were given during the first 210 days of the calves' lives, but only 61.8 per cent of the total quantity of antimicrobial drugs was consumed during this period . The most common diseases from birth until 210 days were respiratory diseases and diarrhoea; treatments for mastitis and interdigital phlegmon (foul in the foot) were more common after 420 days of age . Slightly more than 60 per cent of the treatments were given by the farmers without prior consultation with a veterinary surgeon. Analyst, 2004 Mar, 129(3), 276 - 81 Epub 2004 Jan 20. Semicarbazide is a minor thermal decomposition product of azodicarbonamide used in the gaskets of certain food jars; Stadler RH et al.; Evidence is presented for the first time showing that semicarbazide (SEM) is a minor thermal decomposition product of the blowing agent azodicarbonamide (ADC) . A novel direct analytical method based on liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESIMS/MS) has been developed to determine SEM in foamed polyvinyl chloride (PVC) seals of metal lids, as well as in commercially available ADC . The direct LC-MS/MS method for gaskets entails extraction of the gaskets in hot water, addition of ((15)N(2)(13)C)-SEM as internal standard, and injection of an aliquot directly into the LC-MS system, achieving good sensitivity (S/N = 348 for 2 ng injected on-column) and monitoring three characteristic mass transitions (m/z 76-->31; 76 -->44; 76-->59) . Semicarbazide can be detected in thermally treated ADC, reaching up to 0.93 mmol mol(-1) at 220 degrees C, as determined by the direct LC-MS/MS method . This new method is also compared to the classical derivatization method using 2-nitrobenzaldehyde (2-NBA) that is routinely employed to determine SEM as an indicator of the usage of the antimicrobial drug nitrofurazone, the use of which is not authorized in the European Union (EU) . Both methods revealed proportional results, with approx . 3-fold higher levels recorded by the direct SEM approach, probably due to differences in the extraction procedures used . A limited survey of plastic seals from used press twist and twist-off metal lids on food jars (non-foamed and foamed) revealed levels of SEM ranging from 2 to 8689 microg kg(-1)(average = 1593 microg kg(-1), n= 57 determinations). Infect Immun, 2004 Mar, 72(3), 1470 - 8 Paneth cell alpha-defensins from rhesus macaque small intestine; Tanabe H et al.; Antimicrobial peptides are secreted by small intestinal Paneth cells as components of innate immunity . To investigate the role of alpha-defensins in enteric host defenses in nonhuman primates, alpha-defensin cDNAs were isolated, alpha-defensin peptides were purified from rhesus macaque small bowel, and the bactericidal activities of the peptides were measured . Six rhesus enteric alpha-defensin (RED) cDNAs, RED-1 to RED-6, were identified in a jejunum cDNA library; the deduced RED peptides exhibited extensive diversity relative to the primary structures of rhesus myeloid alpha-defensins . RED-4 was purified from monkey jejunum, and N-terminal peptide sequencing of putative RED-4 peptides identified two N termini, RTCYCRTGR . and TCYCRTGRC.; these corresponded to alternative N termini for the RED-4 molecules, as deduced from their molecular masses and RED cDNAs . In situ hybridization experiments localized RED mRNAs exclusively to small intestinal Paneth cells . Recombinant RED-1 to RED-4 were purified to homogeneity and shown to be microbicidal in the low micromolar range (</=10 micro g/ml) against gram-positive and gram-negative bacteria, with individual peptides exhibiting variable target cell specificities . Thus, compared to myeloid alpha-defensins from rhesus macaques, enteric alpha-defensin peptides are highly variable in both primary structure and activity . These studies should facilitate further analyses of the role of alpha-defensins in primate enteric immunity. Infect Immun, 2004 Mar, 72(3), 1257 - 64 STAT1 is essential for antimicrobial effector function but dispensable for gamma interferon production during Toxoplasma gondii infection; Gavrilescu LC et al.; The opportunistic protozoan Toxoplasma gondii is a prototypic Th1-inducing pathogen inducing strong gamma interferon (IFN-gamma) cytokine responses that are required to survive infection . Intracellular signaling intermediate STAT1 mediates many effects of IFN-gamma and is implicated in activation of T-bet, a master regulator of Th1 differentiation . Here, we show that T . gondii-infected STAT1-null mice fail to upregulate the IFN-gamma-dependent effector molecules inducible nitric oxide synthase (iNOS), IGTP, and LRG-47, which are required for mice to survive infection . Both T-bet and interleukin-12 receptor beta2 (IL-12Rbeta2) failed to undergo normal upregulation in response to T . gondii . Development of IFN-gamma-producing CD4(+) and CD8(+) T lymphocytes was severely curtailed in the absence of STAT1, but a substantial level of STAT1-independent non-T-cell-derived IFN-gamma was induced . Absence of STAT1 also resulted in increased IL-4, Arg1, Ym1, and Fizz1, markers of Th2 differentiation and alternative macrophage activation . Together, the results show that T . gondii induces STAT1-dependent T-lymphocyte and STAT1-independent non-T-cell IFN-gamma production, but that effector functions of this type 1 cytokine cannot operate in the absence of STAT1, resulting in extreme susceptibility to acute infection. Biochem J, 2004 Jun 1, 380(Pt 2), 385 - 92 Comparison of the microbicidal and muramidase activities of mouse lysozyme M and P; Markart P et al.; Lysozyme is one of the most abundant antimicrobial proteins in the airspaces of the lung . Mice express two lysozyme genes, lysozyme M and P, but only the M enzyme is detected in abundance in lung tissues . Disruption of the lysozyme M locus significantly increased bacterial burden and mortality following intratracheal infection with a Gram-negative bacterium . Unexpectedly, significant lysozyme enzyme activity (muramidase activity) was detected in the airspaces of uninfected lysozyme M-/- mice, amounting to 25% of the activity in wild-type mice . Muramidase activity in lysozyme M-/- mice was associated with increased lysozyme P mRNA and protein in lung tissue and bronchoalveolar lavage fluid respectively . The muramidase activity of recombinant lysozyme P was less than that of recombinant M lysozyme . Recombinant P lysozyme was also less effective in killing selected Gram-negative bacteria, requiring higher concentrations than lysozyme M to achieve the same level of killing . The lower antimicrobial activity of P lysozyme, coupled with incomplete compensation by P lysozyme in lysozyme M-/- mice, probably accounts for the increased susceptibility of null mice to infection . Recombinant lysozyme M and P were equally effective in killing selected Gram-positive organisms . This outcome suggests that disruption of both M and P loci would significantly increase susceptibility to airway infections, particularly those associated with colonization by Gram-positive organisms. J Formos Med Assoc, 2003 Dec, 102(12), 840 - 4 Development of multifocal duodenal erosions after anti-Helicobacter pylori triple therapy; Chang CC et al.; BACKGROUND AND PURPOSE: Anti-Helicobacter pylori triple therapy is effective for healing duodenal ulcer (DU) diseases and reducing disease recurrence . However, multifocal duodenal erosions or shallow ulcers may develop after triple therapy . The purpose of this study was to investigate the incidence and outcome of duodenal erosions that developed after triple therapy . METHODS: A total of 106 Taiwanese with active DU and with H . pylori infection were enrolled in this study . All patients received anti-H . pylori triple therapy (i.e., 2 weeks of antimicrobial agents combined with treatment for 4 to 6 weeks with acid suppression agents) . Follow-up endoscopy was performed immediately after stopping treatment . The incidence of multifocal erosions or shallow ulcers over the bulb and/or second portion of the duodenum was studied . Additional acid suppression agent was given for 4 weeks whenever duodenal erosions or shallow ulcers were found . RESULTS: Out of 106 patients, 11 (10.4%) were found to have multifocal duodenal erosions and/or shallow ulcers on the duodenal bulb and/or second portion of the duodenum at the end of treatment . Ten of the 11 patients with newly developed erosions had healed DU in the S1 or S2 stage, and all 11 had successful H . pylori eradication . The duodenal erosions and/or shallow ulcers of these 11 patients were healed after an additional 4 weeks of histamine-2-receptor antagonist therapy . CONCLUSIONS: Multifocal duodenal erosions and/or shallow ulcers were noted in around 10% of Taiwanese DU patients who received anti-H . pylori triple therapy . An additional 4 weeks therapy with acid suppression agents healed these lesions. Methods Mol Biol, 2004, 263, 33 - 44 Multiparameter flow cytometry of bacteria; Shapiro HM et al.; The small size of bacteria makes some microbial constituents undetectable or measurable with only limited precision by flow cytometry . Bacteria may also behave differently from eukaryotes in terms of their interaction with dyes, drugs, and other reagents . It is therefore difficult to design multiparameter staining protocols that work, unmodified, across a wide range of bacterial species . This chapter describes reliable flow cytometric methods for assessment of the physiologic states of Gram-negative organisms, on the one hand, and Gram-positive organisms, on the other, based on measurement of membrane potential and membrane permeability . These techniques are useful in the assessment of effects of environmental conditions and antimicrobial agents on microorganisms. Nat Prod Res, 2004 Feb, 18(1), 85 - 8 A new flavonoid and sulphur-containing amides from Glycosmis chlorosperma; Rahmani M et al.; A new flavonoid, dihydroglychalcone-A, was isolated from the leaves extract of Glycosmis chlorosperma in addition to two known sulphur-containing amides, dambullin and gerambullin . The structure of the new compound was assigned as 2'-hydroxy-4,6'-dimethoxy-3',4'-(2",2"-dimethylpyrano)dihydrochalcone . The extract of the leaves was also found to exhibit antimicrobial and cytotoxic activities. Am J Vet Res, 2004 Feb, 65(2), 131 - 7 Effects of bovine lactoferrin hydrolysate on the in vitro antimicrobial susceptibility of Escherichia coli strains isolated from baby pigs; Chen PW et al.; OBJECTIVE: To determine the antibacterial activity of bovine lactoferrin hydrolysate (bLf-lysate) alone or in combination with other antimicrobials against antimicrobial-resistant Escherichia coli strains isolated from baby pigs . SAMPLE POPULATION: 3 clinical strains of E coli were isolated from baby pigs with severe diarrhea and designated as strains 9061, 9062, and 9065 . PROCEDURE: The broth microdilution checkerboard and fractional inhibitory (or bactericidal) concentration index were used to evaluate the antibacterial effect elicited by bLf-lysate in combination with kanamycin, gentamicin, cephalothin, cefamandole, penicillin G, ampicillin, tetracycline, erythromycin, or rifampicin against the 3 strains of E coli . RESULTS: The 3 strains of E coli were susceptible to gentamicin and rifampicin but highly resistant to most of the other antimicrobials tested, except for strain 9061 that was also susceptible to cephalothin but intermediately inhibited by kanamycin and cefamandole . Synergistic growth-inhibitory activity was observed between bLf-lysate and gentamicin against 1 strain of E coli (strain 9062); synergistic bactericidal activity was found between bLf-lysate and rifampicin against all 3 strains of E coli . Moreover, partial synergy was observed between bLf-lysate and kanamycin, gentamicin, cephalothin, or cefamandole against the strains of E coli, but this partial synergistic activity was mostly seen against only 1 of the strains . Little interaction between bLf-lysate and tetracycline, ampicillin, penicillin G, or erythromycin was observed against the clinical strains of E coli . CONCLUSIONS AND CLINICAL RELEVANCE: A combination of bLf-lysate and certain antimicrobials may prove clinically effective against antimicrobial-resistant strains of E coli. Orv Hetil, 2003 Dec 21, 144(51), 2531 - 3 {Chronic recurrent multifocal osteomyelitis}; Kiraly B et al.; The chronic recurrent multifocal osteomyelitis has been reported very rarely in the literature . However, its significance must be emphasized, because it is a spontaneously healing, benign disease, as compared to the classical forms of osteomyelitis . It leaves behind almost no residual symptoms, and many operations, long antimicrobial therapy may be avoided by diagnosing it . In this case report the authors provide the review of the disease through the history of a 9-year-old boy. Recenti Prog Med, 2003 Dec, 94(12), 554 - 9 {Non-tubercular and non-brucellar spondylodiscitis: preliminary clinico-microbiologic analysis of 37 cases}; Bianco G et al.; Disk-space infection caused by organisms other than Mycobacterium tuberculosis or Brucella species seems to be an emerging disease due to an increase of the population at risk . However, few data are presently available from Italian institutions . In this article we report our "tot" month prospective experience on etiology and clinical presentation of disk-space infections in relation to their community (COM) or nosocomial (postoperative {POS} or non-postoperative {NPOS}) acquisition . Major results were: 1) a different microbial distribution among etiologies of COM, NPOS and POS infections; 2) more frequent distance infection as predisponing factor among NPOS infection than among COM and NPOS ones; 3) absence of fever and more frequent radicular extension of pain among POS infections . Due to the numerous potential microbial etiologies, culture of TC guided-disk aspirated material is of paramount importance for pathogen-targeted antimicrobial therapy. Cochrane Database Syst Rev . 2004;(1):CD000219. Antibiotics for acute otitis media in children; Glasziou PP et al.; BACKGROUND: Acute otitis media is one of the most common diseases in early infancy and childhood . Antibiotic use for acute otitis media varies from 31% in the Netherlands to 98% in the USA and Australia . OBJECTIVES: The objective of this review was to assess the effects of antibiotics for children with acute otitis media . SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE, Index Medicus (pre 1965), Current Contents and reference lists of articles from 1958 to January 2000 . The search was updated in 2003 . SELECTION CRITERIA: Randomised trials comparing antimicrobial drugs with placebo in children with acute otitis media . DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trial quality and extracted data . MAIN RESULTS: Ten trials were eligible based on design, only eight of the trials, with a total of 2,287 children, included patient-relevant outcomes . The methodological quality of the included trials was generally high . All trials were from developed countries . The trials showed no reduction in pain at 24 hours, but a 30% relative reduction (95% confidence interval 19% to 40%) in pain at two to seven days . Since approximately 80% of patients will have settled spontaneously in this time, this means an absolute reduction of 7% or that about 15 children must be treated with antibiotics to prevent one child having some pain after two days . There was no effect of antibiotics on hearing problems of acute otitis media, as measured by subsequent tympanometry . However, audiometry was done in only two studies and incompletely reported . Nor did antibiotics influence other complications or recurrence . There were few serious complications seen in these trials: only one case of mastoiditis occurred in a penicillin treated group . REVIEWER'S CONCLUSIONS: Antibiotics provide a small benefit for acute otitis media in children . As most cases will resolve spontaneously, this benefit must be weighed against the possible adverse reactions . Antibiotic treatment may play an important role in reducing the risk of mastoiditis in populations where it is more common. Cochrane Database Syst Rev . 2004;(1):CD000022. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care; Liberati A et al.; BACKGROUND: Pneumonia is an important cause of mortality in intensive care units . The incidence of pneumonia in such patients ranges between 7% and 40%, and the crude mortality from ventilator associated pneumonia may exceed 50% . Although not all deaths in patients with this form of pneumonia are directly attributable to pneumonia, it has been shown to contribute to mortality in intensive care units independently of other factors that are also strongly associated with such deaths . OBJECTIVES: The objective of this review was to assess the effects of antibiotics for preventing respiratory tract infections and overall mortality in adults receiving intensive care . SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2003), which contains the Acute Respiratory Infections (ARI) Group specialised trials register; MEDLINE (January 1966 to September 2003); EMBASE (January 1990 to September 2003); proceedings of scientific meetings and reference lists of articles from January 1984 to December 2002 . We also contacted investigators in the field . SELECTION CRITERIA: Randomised trials of antibiotic prophylaxis for respiratory tract infections and deaths among adult intensive care unit patients . DATA COLLECTION AND ANALYSIS: At least two reviewers independently extracted data and assessed trial quality . MAIN RESULTS: Overall 36 trials involving 6922 people were included . There was variation in the antibiotics used, patient characteristics and risk of respiratory tract infections and mortality in the control groups . In 17 trials (involving 4295 patients) that tested a combination of topical and systemic antibiotic, the average rates of respiratory tract infections and deaths in the control group were 36% and 29% respectively . There was a significant reduction of both respiratory tract infections (odds ratio 0.35, 95% confidence interval 0.29 to 0.41) and total mortality (odds ratio 0.78, 95% confidence interval 0.68 to 0.89) in the treated group . On average 5 patients needed to be treated to prevent one infection and 21 patients to prevent one death . In 17 trials (involving 2664 patients) that tested topical antimicrobials alone (or comparing topical plus systemic versus systemic alone) the rates of respiratory tract infections and deaths in the control groups were 30% and 26% respectively . There was a significant reduction of respiratory tract infections (odds ratio 0.52, 95% confidence interval 0.43 to 0.63) but not in total mortality (odds ratio 0.97, 95% confidence interval 0.81 to 1.16) in the treated group . REVIEWER'S CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics reduces respiratory tract infections and overall mortality in adult patients receiving intensive care . A treatment based on the use of topical prophylaxis alone reduces respiratory infections but not mortality . The risk of occurrence of resistance as a negative consequence of antibiotic use was appropriately explored only in the most recent trial by de Jonge which did not show any such effect. Q J Nucl Med, 2003 Dec, 47(4), 279 - 91 Non-oncologic applications of radiolabeled peptides in nuclear medicine; Knight LC; Radiolabeled peptides have been investigated for diagnostic imaging in a variety of non-oncologic diseases . For imaging thromboembolic disease, peptides which bind to various components of thrombi have been tested . For targeting the fibrin component of thrombi, peptide analogues of fibrin or fragments of fibronectin which have a distinct binding domain for fibrin have been studied . For targeting activated platelets within thrombi, linear and cyclic peptide antagonists of the glycoprotein IIb/IIIa receptor on platelets have been studied, as well as naturally occurring antagonists of this receptor which are found in venoms . Analogues of laminin and thrombospondin which bind to other receptors on platelets have also been tested . There is an approach which uses a peptide to target thrombin which is sequestered within a fibrin clot . Another area of investigation has been to develop an improved radiopharmaceutical for imaging sites of infection and/or inflammation . Peptides which would bind to leukocytes in vivo, such as antagonists to the tuftsin receptor, chemotactic peptides, interleukin-8, or a platelet factor 4 analogue, have been radiolabeled for this purpose . These agents would enable imaging of both infection and inflammation . Development of a radiopharmaceutical for specifically imaging infection has focused on antimicrobial peptides such as human neutrophil defensin, ubiquicidin, human lactoferrin and alafosfalin, which are expected to bind selectively to microorganisms and not to leukocytes . Radiolabeled peptides are also being explored as agents for assessing unstable atherosclerotic plaque (endothelin), amyloid deposits (amyloid beta peptides), and the consequences of diabetes mellitus (human C-peptide). J Antimicrob Chemother, 2004 Apr, 53(4), 604 - 8 Epub 2004 Feb 18. In vitro susceptibility of Stenotrophomonas maltophilia isolates: comparison of disc diffusion, Etest and agar dilution methods; Nicodemo AC et al.; The disc diffusion, Etest and agar dilution techniques were compared to evaluate the antimicrobial susceptibility profile of 70 Stenotrophomonas maltophilia isolates to seven antimicrobial agents . The S . maltophilia isolates were consecutively collected from May 2000 to May 2002 from individual patients, who were hospitalized in a private Brazilian hospital . The antimicrobial susceptibility tests were carried out and interpreted according to the National Committee for Clinical Laboratory Standards (NCCLS) recommendations . The Etest was carried out according to the manufacturer's instructions . There was good agreement among the distinct susceptibility testing results for chloramphenicol, doxycycline, gatifloxacin, trimethoprim-sulfamethoxazole and ticarcillin-clavulanate, suggesting that the disc diffusion and Etest methods are reliable for testing this group of antimicrobials against S . maltophilia . In contrast, a weak correlation was found between the disc diffusion and agar dilution techniques for testing polymyxin B and colistin with unacceptable very major error rates (18.1% and 22.7% for polymyxin B and colistin, respectively) . Trimethoprim- sulfamethoxazole (MIC50, 0.06 mg/L; 98.5% susceptible) and gatifloxacin (MIC50, 0.12 mg/L; 98.5% susceptible) were the most potent antimicrobial agents tested against S . maltophilia isolates . In contrast, the worst in vitro activity was found for ticarcillin-clavulanate (MIC50, 16 mg/L; 59.1% susceptible) . Although our results confirm that trimethoprim-sulfamethoxazole, gatifloxacin and doxycycline have an excellent in vitro activity against S . maltophilia, further clinical studies are necessary to evaluate the clinical efficacy of these compounds for the treatment of S . maltophilia infections, since no randomized controlled trials have been carried out and no correlation between the clinical response and susceptibility testing results has been reported. J Bacteriol, 2004 Mar, 186(5), 1270 - 9 The PhoP-PhoQ two-component regulatory system of Photorhabdus luminescens is essential for virulence in insects; Derzelle S et al.; Photorhabdus luminescens is a symbiont of entomopathogenic nematodes . Analysis of the genome sequence of this organism revealed a homologue of PhoP-PhoQ, a two-component system associated with virulence in intracellular bacterial pathogens . This organism was shown to respond to the availability of environmental magnesium . A mutant with a knockout mutation in the regulatory component of this system (phoP) had no obvious growth defect . It was, however, more motile and more sensitive to antimicrobial peptides than its wild-type parent . Remarkably, the mutation eliminated virulence in an insect model . No insect mortality was observed after injection of a large number of the phoP bacteria, while very small amounts of parental cells killed insect larvae in less than 48 h . At the molecular level, the PhoPQ system mediated Mg(2+)-dependent modifications in lipopolysaccharides and controlled a locus (pbgPE) required for incorporation of 4-aminoarabinose into lipid A . Mg(2+)-regulated gene expression of pbgP1 was absent in the mutant and was restored when phoPQ was complemented in trans . This finding highlights the essential role played by PhoPQ in the virulence of an entomopathogen. Diagn Microbiol Infect Dis, 2004 Feb, 48(2), 125 - 30 Pharmacokinetic/pharmacodynamic modeling can help guide targeted antimicrobial therapy for nosocomial gram-negative infections in critically ill patients; Mohr JF et al.; Critically ill patients have altered pharmacokinetics (PK) that need to be considered when choosing and dosing antibiotics . We conducted a prospective, observational study to assess clinical and microbiologic response rates in 19 critically ill patients with nosocomial Gram-negative infections . Antibiotics were dosed based on a mathematical pharmacodynamic (PD) model accounting for these altered kinetic parameters . The average APACHE II score +/- SE on intensive care unit admission and at the time of infection was 13.6 +/- 1.2 and 14.6 +/- 1.1, respectively . With targeted antimicrobial therapy adjusted to achieve an optimal PD profile, 17/19 (89%) patients had a clinical cure or improvement and 16/19 (84%) had either microbiologic eradication or presumed eradication . Modeling PD in these critically ill patients resulted in good clinical and microbiologic outcomes. Phytomedicine, 2004 Jan, 11(1), 36 - 42 Characteristics, clinical effect profile and tolerability of a nasal spray preparation of Artemisia abrotanum L . for allergic rhinitis; Remberg P et al.; A nasal spray formulation containing an extract of Artemisia abrotanum L . was developed for therapeutic use in patients with allergic rhinitis and other upper airway disorders . The nasal spray preparation used contains a mixture of essential oils (4 mg/ml) and flavonols (2.5 microg/ml), of which some components have been shown to possess antiinflammatory, expectorant, spasmolytic as well as antiseptic and antimicrobial activities . The most important constituents in the essential oil fraction of the preparation are 1,8-cineole, linalool and davanone, while the flavonol fraction contains centauredin, casticin and quercetin dimethyl-ethers . No trace of thujon was observed in the essential oil of the Artemisia abrotanum L . genotype "Tycho" used for the manufacture of the nasal spray preparation . In 12 patients with diagnoses of allergic rhinitis, allergic conjunctivitis and/or bronchial obstructive disease, the nasal spray was given immediately after the appearance of characteristic allergic nasal symptoms . In 10 of the 12 patients, allergic rhinitis with nasal congestion, sneezing and rhinorrhea was dominant . After administration of the nasal spray, all patients experienced a rapid and significant symptom relief of nasal symptoms, comparable to the effect of antihistamine and chromoglicate preparations which several of the patients had used previously . The effect was present within 5 minutes after the administration and lasted for several hours . In 7 of the 10 rhinitis patients with concomitant symptoms of allergic conjunctivitis, a significant subjective relief of eye symptoms was also experienced . In 3 of the 6 patients who had a history of characteristic symptoms of endogenous, exogenous or exercise induced bronchial obstructive disease, there was a bronchial symptom relief by the nasal spray preparation which was experienced as rapid and clinically significant . It is concluded from the present proof of concept study, that a nasal spray formulation containing an extract characterised by a mixture of essential oils and flavonols from the Artemisia abrotanum L . genotype "Tycho", appears to be clinically useful and suitable for the prophylactic and therapeutic management of patients with allergic rhinitis and adjuvant symptoms. Boll Chim Farm, 2003 Dec, 142(10), 450 - 3 Synthesis and biological activity of a novel series of 4-{2'-(6'-nitro)benzimidazolyl}benzoyl amino acids and peptides; Himaja M et al.; A series of new 4-{2'-(6'-nitro)benzimidazolyl}benzoyl amino acids and peptides have been synthesized by coupling the 4-{2'-(6'-nitro)benzimidazolyl}benzoic acid with amino acid methyl esters/dipeptides using DCC as the coupling agent . All the synthesized compounds were found to exhibit potent anthelmintic activity along with moderate antimicrobial activity. Boll Chim Farm, 2003 Nov, 142(9), 396 - 405 Pyrimidines . Part II: Synthesis of novel pyrimidines, 1,2,4-triazolo{4,3-a}pyrimidin-7-ones and pyrimidino{2,1-c}{1,2,4}triazin-8-ones for their antimicrobial and anticancer activities; Habib NS et al.; Five main classes of novel pyrimidine derivatives have been synthesized; namely 6-substituted phenyl-5-cyano-3-methyl-2-phenacylhydrazino-3,4-dihydropyrimidin-4-ones 4a-e; 6-substituted phenyl-2-arylidene hydra-zino-5-cyano-3-methyl-3,4-dihydropyrimidin-4-ones 5a-i; 6-substituted phenyl-2-acylhydrazino-5-cyano-3-methyl-3,4-dihydropyrimidin-4-ones 7a-d, 8a-e and 9a-c; three novel series of 1,2,4-triazolo{4,3-a} pyrimidones 10a,b, 11a-d and 12a-d and 6-substituted phenyl-7-cyano-9-methyl-3-phenyl or 4-chlorophenyl-4,9-dihydropyrimido{2,1-c}{1,2,4} triazin-8-ones 13a-c . Besides, the azide compound 2-azido-5-cyano-3-methyl-6-phenyl-3,4-dihydropyrimidin-4-one 6 was also synthesized . The prepared compounds were tested for antimicrobial and anticancer activity . Compounds 4b and 4d showed promising activity against Escherichia coli . Compounds 3c, 5c, 5e, 5g and 7b were active in the three cell line antitumor one dose primary assay and were evaluated in the 60 human tumor full panel cell line invitro screening . Compound 5c showed promising activity against all types of leukemia especially leukemia K-562 and leukemia SR with GI50 = 1.61 and 2.63 mmol/l respectively. Ann Periodontol, 2003 Dec, 8(1), 79 - 98 Local anti-infective therapy: pharmacological agents . A systematic review; Hanes PJ et al.; BACKGROUND: It is well recognized that periodontal diseases are bacterial in nature . An essential component of therapy is to eliminate or control these pathogens . This has been traditionally accomplished through mechanical means (scaling and root planing {SRP}), which is time-consuming, difficult, and sometimes ineffective . Over the past 20 years, locally delivered, anti-infective pharmacological agents, most recently employing sustained-release vehicles, have been introduced to achieve this goal . RATIONALE: This systematic review evaluates literature-based evidence in an effort to determine the efficacy of currently available anti-infective agents, with and without concurrent SRP, in controlling chronic periodontitis . FOCUSED QUESTION: In patients with chronic periodontitis, what is the effect of local controlled-release anti-infective drug therapy with or without SRP compared to SRP alone on changes in clinical, patient-centered, and adverse outcomes? SEARCH PROTOCOL: MEDLINE, the Cochrane Central Trials Register, and Web of Science were searched . Hand searches were performed of the Journal of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal Research . Searches were performed for articles published through April 2002 . In addition, investigators contacted editors of the above-mentioned journals and companies sponsoring research on these agents for related unpublished data and studies in progress . SELECTION CRITERIA: INCLUSION CRITERIA: Studies included randomized controlled clinical trials (RCT), and case-controlled and cohort studies at least 3 months long . Therapeutic interventions had to include 1) SRP alone; 2) local anti-infective drug therapy and SRP; or 3) local anti-infective drug therapy alone . Included studies had to report patient-based mean values and measures of variation for probing depth (PD) and/or clinical attachment levels (CAL) for both test and control groups . EXCLUSION CRITERIA: Studies were excluded if they: 1) included data from a previously published article; 2) included daily rinsing with chlorhexidine (CHX); or 3) had unclear descriptions of randomization procedures, examiner masking, or concomitant therapies . DATA COLLECTION AND ANALYSIS: For the meta-analysis, PD and CAL were expressed as summary mean effects with 95% confidence intervals (CI) for the effect, and analyzed using a standardized difference between SRP alone and experimental agent groups . The results were assessed with both fixed-effects and random-effects models . Studies were ranked according to the York system . MAIN RESULTS: 1 . Thirty-two studies were included (28 RCT, 2 cohort, and 2 case-control), incorporating a total patient population of 3,705 subjects . 2 . Essentially all studies reported substantial reductions in gingival inflammation and bleeding indices, which were similar in both control and experimental groups . 3 . A meta-analysis completed on 19 studies that included SRP and local sustained-release agents compared with SRP alone indicated significant adjunctive PD reduction or CAL gain for minocycline (MINO) gel, microencapsulated MINO, CHX chip and doxycycline (DOXY) gel during SRP compared to SRP alone . 4 . Use of antimicrobial irrigants or anti-infective sustained-release systems as an adjunct to SRP does not result in significant patient-centered adverse events . REVIEWERS' CONCLUSIONS: 1 . In some populations, anti-infective agents in a sustained-release vehicle alone can reduce PD and bleeding on probing (BOP) equivalent to that achieved by SRP alone . 2 . No evidence was found for an adjunctive effect on reduction of PD and BOP of therapist-delivered CHX irrigation during SRP compared to SRP alone . 3 . Additional RCTs are needed which evaluate the effectiveness of these therapies in all forms of periodontitis . 4 . The study protocol for future RCTs should include appropriate statistical analyses and complete data sets to facilitate future evidence-based reviews . 5 . Alternative surrogate parameters to PD and CAL need to be identified and validated such as microbial, inflammatory, or tissue-destructive markers that could be used in conjunction with clinical parameters to help determine the patient's response to emerging technologies that target the infectious and/or inflammatory aspects of periodontitis . 6 . Future Phase IV clinical trials should be designed that evaluate local anti-infective therapies in conjunction with SRP in a manner consistent with current standards of care and evaluate cost-effectiveness . 7 . The use of local anti-infective agents in at-risk patient populations and for the treatment of at-risk disease sites needs to be validated in randomized controlled clinical trials . 8 . Several local anti-infective agents combined with SRP appear to provide additional benefits in PD reduction and CAL gain compared to SRP alone . The decision to use local anti-infective adjunctive therapy remains a matter of individual clinical judgment, the phase of treatment, and the patient's status and preferences. Ann Periodontol, 2003 Dec, 8(1), 12 - 37 Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents . A systematic review; Reddy MS et al.; BACKGROUND: The use of modulating agents, including inhibition of matrix metalloproteinases (MMPs) with antiproteinases, blocking production of proinflammatory cytokines and prostaglandins with anti-inflammatory drugs, and inhibiting activation of osteoclasts with bone-sparing agents, has been postulated to be of therapeutic value as an adjunctive therapy to the management of chronic periodontitis . RATIONALE: The objective of this systematic review of the literature was to assess the adjunctive efficacy of antiproteinase, anti-inflammatory, and bone-sparing host-modulating agents in the treatment of gingivitis, aggressive periodontitis, and chronic periodontitis . FOCUSED QUESTIONS: 1 . In patients with periodontal diseases, what is the effect of host-modulation agents, alone or combined with conventional therapy, compared to conventional therapy alone as assessed by clinical, radiographic, adverse, and patient-centered outcomes? 2 . In patients with dental implants, what is the effect of host-modulation agents on implant success assessed by clinical, radiographic, adverse, and patient-centered outcomes? SEARCH PROTOCOL: MEDLINE, Embase, and the Cochrane Library databases were searched without language restrictions through April 1, 2002 for studies that used tetracycline (TET)-related matrix metalloproteinase (MMP) inhibitors, or non-steroidal anti-inflammatory drugs (NSAIDs) and bisphosphonate anti-osteolytic agents . The investigation also included hand searching of journals and contacting authors and industry experts . SELECTION CRITERIA: INCLUSION CRITERIA: Only human studies (randomized controlled clinical trials, cohort studies, case-control studies, cross-sectional studies, and case series) were selected . Studies were on subjects with gingivitis, aggressive or chronic periodontitis, or dental implants . Interventions included TET-related MMP inhibitors, NSAIDs, or bisphosphonate anti-osteolytic agents . EXCLUSION CRITERIA: Studies that used MMP tissue inhibitors as diagnostic or prognostic indicators of periodontal disease or that evaluated short-term systemic antibodies or locally delivered levels of drugs with antiproteinase activity were excluded . DATA COLLECTION AND ANALYSIS: The primary outcomes for assessment were changes in bone or clinical attachment levels (CAL); secondary outcomes included clinical measures of plaque, gingival inflammation, probing depth (PD), and mobility . Summary data appropriate for meta-analysis were pooled using a weighted average and analyzed using a standardized difference; the results were checked with both fixed-effects and random-effects models . MAIN RESULTS: 1 . A meta-analysis done on the studies reporting changes in CAL and PD following administration of sub-antimicrobial doses of doxycycline (SDD) in conjunction with scaling and root planing (SRP) in patients with periodontitis showed a statistically significant beneficial adjunctive effect . 2 . There were insufficient data to provide meta-analyses on periodontal patients treated with other host-modulating agents; descriptive tables are included . 3 . NSAIDS show promise in their ability to slow periodontal disease . 4 . Preliminary data on bisphosphonate agents indicate there is a potential role for these agents in periodontitis management . 5 . There are a very limited number of studies on host-modulating agents and dental implants and no analyses were possible . 6 . Because the treatment methodologies and clinical variables differed considerably among the studies, it is difficult to summarize the information and identify a reliable total patient population . REVIEWERS' CONCLUSIONS: 1 . Large multi-center trials are needed to evaluate the role of host-modulating agents in the treatment of periodontitis . 2 . NSAIDS and bisphosphonate drugs may have a potential adjunctive role in periodontal therapy . 3 . The adjunctive use of SDD with SRP is statistically more effective than SRP alone in reducing PD and in achieving CAL gain. J Chem Ecol, 2003 Dec, 29(12), 2667 - 81 Induction of hypericins and hyperforins in Hypericum perforatum in response to damage by herbivores; Sirvent TM et al.; Plants respond to herbivore and pathogen attack by a variety of direct and indirect mechanisms that include the induction of secondary metabolites . The phytomedicinal plant Hypericum perforatum L . produces two different classes of secondary metabolites: hyperforins, a family of antimicrobial acylphloroglucinols; and hypericins, a family of phototoxic anthraquinones exhibiting antimicrobial, antiviral, and antiherbivore properties in vitro . To determine whether these compounds are part of the herbivore-specific inducible plant defense system, we used an in vitro detached assay to assess the effects of specialist and generalist herbivore damage on the levels of hypericins and hyperforin . Greenhouse-grown H . perforatum plant sections were challenged with the specialist, Chrysolina quadrigemina, or with one of the following generalist feeders: Spilosoma virginica, Spilosoma congrua, or Spodoptera exigua . Feeding by the specialist beetle or mechanical wounding caused little change in phytochemical levels in plant tissue, whereas the small amount of feeding by the generalists caused 30-100% increases in hypericins and hyperforin as compared to control levels . Although the leaf damage index of the specialist feeding was 2.7 times greater, C . quadrigemina had little effect on H . perforatum chemical defenses in response to feeding damage in comparison to generalist feeding. J Food Prot, 2004 Feb, 67(2), 285 - 94 Cations reduce antimicrobial efficacy of lysozyme-chelator combinations; Boland JS et al.; Reduction of the antimicrobial efficacy of lysozyme-chelator combinations against two Escherichia coli O157:H7 strains on addition of mineral salts was studied . The objective of the study was to determine the effect of type and concentration of mono-, di-, and trivalent mineral salts on the antimicrobial effectiveness of lysozyme and various chelators against E . coli O157:H7 . Seven salts (Al3+, Ca2+, Fe2+, Fe3+, K+, Mg2+, and Na+) at 1 to 10 mM were added to aqueous solutions of lysozyme and disodium ethylenediamine tetraacetic acid (EDTA), disodium pyrophosphate (DSPP), or pentasodium tripolyphosphate (PSTPP) at pH 6, 7, or 8 and applied to cultures of E . coli O157:H7 strains 932 and H1730 . Inhibitory activity of lysozyme chelator combinations against both strains was completely lost after addition of > or = 1 mM Ca2+ and Mg2+ at pH 7 and 8 . At pH 6, antimicrobial activity of lysozyme-EDTA against both strains was retained in the presence of calcium or magnesium cations . DSPP-lysozyme inhibited strain H1730 at pH 6 despite the presence of Mg2+ . Concentrations above 4 mM Fe2+ neutralized activity of all lysozyme-chelator combinations . Reversal of inhibition by lysozyme-chelator complexes by the monovalent Na+ and K+ ions depended on E . coli O157:H7 strain type . Neither monovalent cation reversed inhibition of strain 932 . However, Na+ and K+ reversed lysozyme-chelator inhibition of strain H1730 . The addition of > or = 1 mM Fe3+ or Al3+ was effective in reversing inhibition of both strains by lysozyme and EDTA at pH 6, 7, and 8 . Isothermal titration calorimetry was used to determine the amount of ion-specific competitive binding of free cations by EDTA-lysozyme combinations . A mechanistic model for the antimicrobial functionality of chelator-lysozyme combinations is proposed. Int J Food Microbiol, 2004 Feb 15, 91(1), 43 - 50 Effects of peroxyacetic acid, acidified sodium chlorite or lactic acid solutions on the microflora of chilled beef carcasses; Gill CO et al.; The effects of solutions of 0.02% peroxyacetic acid, acidified 0.16% sodium chlorite, 2% lactic acid and 4% lactic acid on the natural flora of the distal surfaces of pieces of brisket, from chilled beef carcass quarters delivered from two slaughtering plants to a processing plant, were investigated . Peroxyacetic acid and acidified sodium chlorite solutions had little effect on the numbers of aerobes, coliforms or Escherichia coli on meat from one plant, and were less effective than 4% lactic acid for reducing the numbers of bacteria on meat from the other plant . With meat from both plants, treatment of meat with 4% lactic acid and holding for 5 or 60 min at 7+/-1 degrees C before sampling resulted in reductions of all three groups of bacteria by >/=1.5 log unit . Treatment with 2% lactic acid resulted in similar reductions when meat was sampled 5 min after the treatment, but reductions were about 1 log unit when meat was sampled 60 min after the treatment . Treatment of carcass quarters with 4% lactic acid resulted in reductions of bacterial numbers of >/=2 log units at distal surfaces, but </=2 log units at medial surfaces . The findings indicate that the efficacies of antimicrobial solutions may be inconsistent when they are applied to chilled meat from different sources and to different types of meat surface, and that bacteria injured by application of an antimicrobial solution may recover during processing of meat at temperatures about 7 degrees C . However, 4% lactic acid may be generally useful as a decontaminant for chilled, raw meat. Int J Radiat Oncol Biol Phys, 2004 Mar 1, 58(3), 674 - 81 A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy; Trotti A et al.; PURPOSE: Oral mucositis (OM) causes significant morbidity during the course of radiotherapy (RT) treatment of head-and-neck cancer . It is hypothesized that infection plays a role in the development of OM . We tested the efficacy of iseganan HCl (iseganan), a synthetic peptide with broad-spectrum antimicrobial activity, for preventing RT-associated OM . METHODS: A multinational, randomized, double-blind, controlled trial was performed on patients receiving primary RT, primary chemoradiotherapy or postoperative RT . Patients were randomized to receive iseganan oral solution plus standard-of-care oral hygiene (SOC), placebo plus SOC, or SOC alone throughout the RT administration period . The severity of OM was assessed by NCI-CTC scoring and clinical symptoms by patient questionnaire . RESULTS: A total of 545 patients were randomized to the study . Nine percent of the patients in both the iseganan and placebo groups did not develop ulcerative OM (Grades 2, 3, 4) (p = 0.998) whereas only 2% of the patients receiving SOC alone remained free of oral ulceration (p = 0.049) . The maximum severity of mouth pain and difficulty swallowing did not differ in patients treated with iseganan or placebo . However, patients in both intervention groups reported less mouth pain and difficulty swallowing than did patients receiving SOC alone . Nausea was the only adverse event that occurred with >/=5% increased frequency in the iseganan group than in either the placebo or SOC groups (51% vs . 42% vs . 46%) . Adverse events leading to study drug discontinuation and death did not differ significantly between groups . CONCLUSION: Iseganan oral solution was safe but did not reduce the risk for developing ulcerative OM relative to placebo . Intensified oral hygiene or the administration of the vehicle used to deliver study drug in this trial appears to have reduced the risk and severity of OM . Our results suggest that antimicrobial intervention may not meaningfully affect the pathogenesis of radiation-induced OM. Rapid Commun Mass Spectrom, 2004, 18(4), 443 - 50 Liquid chromatography/time-of-flight mass spectrometric analyses for the elucidation of the photodegradation products of triclosan in wastewater samples; Ferrer I et al.; Liquid chromatography coupled with time-of-flight mass spectrometry (LC/TOFMS) was applied for the identification of four new photodegradation products of triclosan, a major antimicrobial agent used in personal care products . Wastewater samples, spiked at 7 microg/mL with triclosan, were irradiated with natural sunlight in order to generate the photodegradation products . Aliquots of the spiked water samples were taken at different times of irradiation and compounds were isolated from the water samples by solid-phase extraction . Separation and detection of the compounds and degradation products were accomplished by LC/TOFMS, which provided highly selective information about elemental compositions . Accurate mass measurements for the four degradation products permitted postulation of proposed empirical formulae in this study . Replacement of chlorine atoms by hydroxyl groups and chlorine losses are the major degradation pathways proposed . The degradation products were formed also under environmental conditions in wastewater matrices, thus suggesting their presence in real wastewater treatment processes . Br J Gen Pract, 2004 Jan, 54(498), 20 - 4 A diagnostic rule for the aetiology of lower respiratory tract infections as guidance for antimicrobial treatment; Graffelman AW et al.; BACKGROUND: The majority of patients with lower respiratory tract infections (LRTIs) are treated with antibiotics; some of them are unnecessary because of a viral cause . Information on prediction of the aetiology, especially in a general practice setting, is missing . AIM: To differentiate between viral and bacterial LRTI on simple clinical criteria, easily obtained at the bedside . DESIGN OF STUDY: Prospective observational study . SETTING: General practices in the Leiden region of The Netherlands . METHOD: Adult patients with LRTI were included . Standard medical history and physical examination were performed . Sputum, blood and throat swabs were collected for diagnostic tests . According to microbiological findings, patients were classified as bacterial, viral, dual infection and unknown cause . In a logistic regression model independent predictors were determined . Scoring systems were developed . The accuracies of the diagnostic rules were tested by using receiver operating characteristic (ROC) curves . RESULTS: One-hundred and forty-five patients were classified as having bacterial (n = 35), viral (n = 49), or dual infection (n = 8), or infection of unknown cause (n = 53), respectively . Independent predictors for bacterial infection were fever (odds ratio {OR} = 8.0; 95% confidence interval {CI} = 0.9 to 71.0), headache (OR = 4.3; 95% CI = 1.0 to 19.1) cervical painful lymph nodes (OR = 8.7; 95% CI = 1.1 to 68.0), diarrhoea (OR = 0.3; 95% CI = 0.1 to 1.0) and rhinitis (OR = 0.3; 95% CI = 0.1 to 0.9) . As an additional independent predictor, an infiltrate on chest X-ray (OR = 5.0; 95% CI = 1.2 to 20.5) was found . The diagnostic rules developed from these variables classified the aetiology of LRTI with a ROC curve area of 0.79 (clinical score), 0.77 (simplified score) and 0.83 (extended score) . CONCLUSIONS: A diagnostic rule was developed, based on information that is easy to obtain at the bedside, to predict a bacterial infection . This diagnostic rule may be a tool for general practitioners in their management of patients with LRTI. Protein Pept Lett, 2004 Feb, 11(1), 35 - 40 Effects of two glycine residues in positions 13 and 17 of pleurocidin on structure and bacterial cell selectivity; Lim SS et al.; Pleurocidin (Ple), a 25-residue alpha-helical antimicrobial peptide, isolated from skin mucosa of the winter flounder, shows potent bacterial cell selectivity . In this study, the effect of two glycine residues in positions 13 and 17 of Ple on structure and bacterial cell selectivity was investigated by Gly-->Ala substitution . Ala-substitution (Gly(13, 17)-->Ala, Gly13-->Ala and Gly17-->Ala) in positions 13 and 17 of Ple did not induce a significant change in antibacterial activity, but increased hemolytic activity . Both Gly(13, 17)-->Ala and Gly17-->Ala substitution did not cause a remarkable change in alpha-helical content in SDS micelles, while Gly(13, 17)-->Ala substitution caused a drastic increase in alpha-helical content . These results suggest that the hinge region from Gly13 to Gly17 of Ple is assumed to provide its conformational flexibility and bacterial cell selectivity. J Pediatr Nurs, 2004 Feb, 19(1), 74 - 80 Chlorhexidine versus povidone-iodine for central venous catheter site care in children; Carson SM; The number of children receiving central venous catheters (CVCs) for the administration of medications is at an all-time high . Unfortunately, placement of these CVCs is not without risks . Infection of CVC insertion sites is one of the most common, yet often preventable, causes of nosocomial bacteremia in both children and adults worldwide . Throughout the years, multiple practice recommendations have been made regarding the proper site care of CVCs . The most popular antimicrobial solution used for site care has traditionally been povidone-iodine . Chlorhexidine gluconate solution, however, has been shown to be more effective than povidone-iodine in preventing CVC-related infections in adults . There continues to be controversy regarding the efficacy and safety of antimicrobial solutions for pediatric CVC site care . An evidence-based approach was used to determine current recommendations for CVC site care in children. Arch Dermatol Res, 2004 Apr, 295(11), 474 - 81 Epub 2004 Feb 12. Malassezia furfur induces the expression of beta-defensin-2 in human keratinocytes in a protein kinase C-dependent manner; Donnarumma G et al.; Antimicrobial peptides of the beta-defensin family are expressed in all human epithelial tissues tested to date and have recently been the subject of vigorous investigation . Their localization and characteristics support the hypothesis that these peptides play a role in mucosal and skin defense . The lipophilic yeast Malassezia furfur is a saprophyte found in normal human cutaneous flora . Malassezia furfur is not only a saprophyte, but is also associated with several diseases such as Malassezia folliculitis, seborrheic dermatitis and some forms of atopic dermatitis, psoriasis and confluent and reticulate papillomatosis . Little is known about the mechanism by which M . furfur overcomes the natural barrier of the skin . To further define the role of the beta-defensins in the innate human skin immune response, we analyzed the mRNA expression of two human beta-defensins HBD-1 and HBD-2 in human keratinocytes treated with M . furfur . In addition, we looked into how M . furfur of TGF-beta1 and IL-10, cytokines that interfere with the development of protective cell immunity, regulate their expression . Finally, we examined the signal transduction mechanisms involved during M . furfur uptake . Cultured human keratinocytes were treated with M . furfur . The mRNA and protein expression were analyzed, respectively, by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting . Our data demonstrate that M . furfur does not modify HBD-1 expression, whereas it up-regulates, via protein kinase C (PKC), the expression of HBD-2, TGFbeta-1 and IL-10 48 h after treatment . Our results suggest that beta-defensins are integral components of innate host defenses . They play an essential part in the resistance of the human skin surfaces against M . furfur uptake and other microbial invasion. Mol Biol Evol, 2004 May, 21(5), 819 - 27 Epub 2004 Feb 12. Evidence of positively selected sites in mammalian alpha-defensins; Lynn DJ et al.; Alpha-defensins are a family of mammalian antimicrobial peptides that exhibit variable activity against a panel of microbes, including bacteria, fungi, and enveloped viruses . We have employed a maximum-likelihood approach to detect evidence of positive selection (adaptive evolution) in the evolution of these important molecules of the innate immune response . We have identified 14 amino acid sites that are predicted to be subject to positive selection . Furthermore, we show that all these sites are located in the mature antimicrobial peptide and not in the prepropeptide region of the molecule, implying that they are of functional importance . These results suggest that mammalian alpha-defensins have been under selective pressure to evolve in response to potentially infectious challenges by fast-evolving microbes. J Biol Chem, 2004 Apr 23, 279(17), 17951 - 6 Epub 2004 Feb 11. The human antimicrobial peptide LL-37 transfers extracellular DNA plasmid to the nuclear compartment of mammalian cells via lipid rafts and proteoglycan-dependent endocytosis; Sandgren S et al.; Antimicrobial peptides, such as LL-37, are found both in nonvertebrates and vertebrates, where they represent important components of innate immunity . Bacterial infections at epithelial surfaces are associated with substantial induction of LL-37 expression, which allows efficient lysis of the invading microbes . Peptide-mediated lysis results in the release of bacterial nucleic acids with potential pathobiological activity in the host . Here, we demonstrate that LL-37 targets extracellular DNA plasmid to the nuclear compartment of mammalian cells, where it is expressed . DNA transfer occurred at physiological LL-37 concentrations that killed bacterial cells, whereas virtually no cytotoxic or growth-inhibitory effects were observed in mammalian cells . Furthermore, LL-37 protected DNA from serum nuclease degradation . LL-37.DNA complex uptake was a saturable time- and temperature-dependent process and was sensitive to cholesterol-depleting agents that are known to disrupt lipid rafts and caveolae, as shown by flow cytometry . Confocal fluorescence microscopy studies showed localization of internalized DNA to compartments stained by cholera toxin B, a marker of lipid rafts, but failed to demonstrate any co-localization of internalized DNA with caveolin-positive endocytotic vesicles . Moreover, LL-37-mediated plasmid uptake and reporter gene expression were strictly dependent on cell surface proteoglycans . We conclude that the human antimicrobial peptide LL-37 binds to, protects, and efficiently targets DNA plasmid to the nuclei of mammalian cells through caveolae-independent membrane raft endocytosis and cell surface proteoglycans. Mar Biotechnol (NY), 2002 Jan, 4(1), 81 - 93 Potential indicators of stress response identified by expressed sequence tag analysis of hemocytes and embryos from the American oyster, Crassostrea virginica; Jenny MJ et al.; A pilot program was initiated to identify genes from the American oyster, Crassostrea virginica, that are potentially involved in the stress response for use as bioindicators of exposure to environmental pollutants and to toxic and infectious agents . A PCR-based method was used to construct cDNA libraries from pooled embryos and the hemocytes of a single individual . A total of 998 randomly selected clones (expressed sequence tags, ESTs) were sequenced . Approximately 40% of the ESTs are novel sequences . Several potential biomarkers identified include an antimicrobial peptide, recognition molecules (lectin receptors), proteinases and proteinase inhibitors, and a novel metallothionein . Diversity analysis shows that 363 and 286 unique genes were identified from the hemocyte and embryo libraries, respectively, indicating that full-scale EST collection is a valuable approach for the discovery of new genes of potential significance in the molluscan stress response. Mar Biotechnol (NY), 2002 Jun, 4(3), 294 - 302 Effect of cecropin B and a synthetic analogue on propagation of fish viruses in vitro; Chiou PP et al.; Cecropins and other natural antimicrobial peptides are widely distributed in animals from insects to mammals . These proteins have been shown to be major constituents of the innate immune systems of animals for nonspecific defense of the host against various bacteria and parasites . Therefore, exploitation of this natural innate defense system may lead to the development of effective methods for protecting fish from invasion by microbial pathogens . Recently, we have demonstrated that the introduction of cecropin transgenes into Japanese medaka (Oryzias latipes) conferred resistance to infection by fish bacterial pathogens . Aside from a few reports documenting the antiviral effect of antimicrobial peptides including cecropins against mammalian viruses, there is no evidence for the effect of these peptides against fish viruses . In this article we present results of in vitro characterization of native cecropin B and a synthetic analogue, CF17, against several important fish viral pathogens--namely, infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic septicemia virus (VHSV), snakehead rhabdovirus (SHRV), and infectious pancreatic necrosis virus (IPNV) . Upon coincubation of these peptides and viruses, the viral titers yielded in fish cells were reduced from several fold to 104-fold . Direct disruption of the viral envelope and disintegration of the viral capsids may be involved in the inhibition of viral replication by the peptides . Results of our studies demonstrate the potential of manipulating antimicrobial peptide genes by transgenesis to combat viral infection in fish. Mar Biotechnol (NY), 2002 Jun, 4(3), 278 - 93 Crustins, homologues of an 11.5-kDa antibacterial peptide, from two species of penaeid shrimp, Litopenaeus vannamei and Litopenaeus setiferus; Bartlett TC et al.; The response of crustaceans to pathogens is believed to depend solely on innate, nonadaptive immune mechanisms, including phagocytosis, encapsulation, clotting, and a variety of soluble antimicrobial activities . Arthropod antimicrobial peptides, while characterized primarily from insects, also have been isolated from crustaceans . Expressed sequence tag analysis of hemocyte complementary DNA libraries from 2 species of shrimp, Litopenaeus vannamei and Litopenaeus setiferus, revealed transcripts with strong sequence similarity to an 11.5-kDa antibacterial peptide (crustin Cm1) found in Carcinus maenas . Crustins were also observed to contain motifs common to proteinase inhibitors . Analysis of these cDNA libraries yielded at least 3 different isoforms of this peptide in L . vannamei (crustin Lv1-Lv3) and 3 in L . setiferus (crustin Ls1-Ls3) . Further analysis of a second L . vannamei cDNA library revealed the presence of 3 more possible isoforms (crustin Lv4-Lv6), which differed from those seen in the first L . vannamei cDNA library . Genomic Southern blot analysis revealed a complex family of crustin-related sequences . However, full-length crustin appears to be encoded by a much more restricted subset of sequences within this family. Mar Biotechnol (NY), 2002 Sep, 4(4), 431 - 40 Antifouling activities of N-substituted imides: antimicrobial activities and inhibition of Mytilus edulis phenoloxidase; Zentz F et al.; In the search for novel biodegradable antifouling agents, a series of imides (N-substituted maleimides and succinimides) have been synthesized . A large majority of N-substituted maleimides and succinimides showed an antimicrobial activity toward gram-positive and gram-negative bacteria and fungi of marine origin with minimal inhibition concentrations in the range of 6 to 24 microg/ml . The imides with an alkyl substituent showed higher activities than aromatic analogues, but structure-activity relationships were not clearly established . Some compounds were powerful inhibitors of Mytilus edulis phenoloxidase . This inhibition was noncompetitive as demonstrated with 2 maleimides, a 3-acetoxy succinimide and a succinimide . Thus, this family of products has potential interest as antifouling agents. Mar Biotechnol (NY), 2002 Oct, 4(5), 487 - 94 Identification of Immune-Related Genes in Hemocytes of Black Tiger Shrimp (Penaeus monodon); Supungul P et al.; An expressed sequence tag (EST) library was constructed from hemocytes of the black tiger shrimp (Penaeus monodon) to identify genes associated with immunity in this economically important species . The number of complementary DNA clones in the constructed library was approximately 4 x 105 . Of these, 615 clones having inserts larger than 500 bp were unidirectionally sequenced and analyzed by homology searches against data in GenBank . Significant homology to known genes was found in 314 (51%) of the 615 clones, but the remaining 301 sequences (49%) did not match any sequence in GenBank . Approximately 35% of the matched ESTs were significantly identified by the BLASTN and BLASTX programs, while 65% were recognized only by the BLASTX program . Of the 615 clones, 55 (8.9%) were identified as putative immune-related genes . The isolated genes were composed of those coding for enzymes and proteins in the clotting system and the prophenoloxidase-activating system, antioxidative enzymes, antimicrobial peptides, and serine proteinase inhibitors . Three full-length ESTs encoding antimicrobial peptides (antilipopolysaccharide and penaeidin homologues) and a heat shock protein (cpn10 homologue) are reported. Ophthalmologe, 2004 Jan, 101(1), 19 - 24 {Tear outflow . Impact of mucins and TFF-peptides}; Paulsen F et al.; The epithelial lining of the lacrimal sac and the nasolacrimal duct consists of pseudo-stratified, columnar epithelia rich in goblet cells . Major secretory products of the epithelial cells are mucins together with TFF peptides . Expression and distribution of several mucins and TFF peptides in the human efferent tear ducts was investigated by means of reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry . mRNAs for all the mucins investigated, MUC1, MUC2, MUC4, MUC5AC, MUC5B and MUC7, were detected in healthy human lacrimal sacs and nasolacrimal ducts . Both MUC5AC and MUC5B were detected in goblet cells forming intraepithelial mucous glands . MUC7 together with TFF3 occurred only in columnar epithelial cells of the efferent tear duct system . The mucin diversity of the efferent tear ducts could enhance tear transport and antimicrobial defense . The absence of some mucins in non-functioning although patent segments of the lacrimal passage, suggests that mucins ease tear flow through the efferent tear ducts because these conditions are associated with epiphora . Disorders in the balance of single mucins could be of importance with regard to dacryostenosis, dacryocystitis and dacryolith formation. Pediatr Infect Dis J, 2004 Feb, 23(2), 181 - 3 Antimicrobial prescribing for otitis externa in children; McCoy SI et al.; We describe the patterns of antimicrobial prescribing and trends in disease occurrence among children with otitis externa using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 1995 to 2000 . Oral antimicrobial therapy for otitis externa is more likely to contribute to antimicrobial resistance than is topical antimicrobial therapy and is rarely indicated . Thirty-nine percent of visits resulted in a prescription for topical antibiotics, and 25% of visits resulted in a prescription for oral antibiotics . Inappropriate antimicrobial prescribing for otitis externa occurs frequently. Pediatr Infect Dis J, 2004 Feb, 23(2), 145 - 51; discussion 151-5 Clinical predictors of bloodstream infections and mortality in hospitalized Malawian children; Norton EB et al.; BACKGROUND: In sub-Saharan Africa, bloodstream infections (BSI) are a major cause of pediatric mortality . Because of limited resources and facilities in these developing countries, treatment often must be based solely on clinical observations and patient history and includes the use of broad spectrum antimicrobials, a factor in the emergence of antibiotic resistance . METHODS: During July 28 through August 18, 1998 we analyzed clinical, epidemiologic and microbiologic data from a cohort of 225 hospitalized children in Malawi, Africa, to determine clinical indices associated with the presence/absence of BSI and/or mortality for use in settings with minimal microbiologic laboratory and intensive care facilities . RESULTS: BSI (n = 35 children) were associated with malnutrition, chronic cough, lethargy by history, lethargy on examination and oral thrush; 92% of children without these symptoms were BSI-negative . Mortality (21 of 173 children with known mortality status) was associated with malnutrition, lethargy on examination, prior receipt of antimalarials and acute decreased feeding . Of those with > or =2 of these indices 69% died; of those with <2 of the indices 94% survived . Infection with human immunodeficiency virus was not significantly related to either BSI or mortality status . CONCLUSIONS: Malnutrition, but not HIV, was strongly related to both BSI and mortality . Assessment of these BSI and mortality indices at hospital admission provides rapid, cost-free indication of which children are most/least in need of empiric antimicrobial therapy or intensive observation, thereby maximizing appropriate use of antimicrobials and limited facilities while minimizing inappropriate antimicrobial usage. Chest, 2004 Feb, 125(2 Suppl), 52S - 60S; quiz 60S-61S Macrolides for the treatment of chronic sinusitis, asthma, and COPD; Gotfried MH; In addition to their well-known antimicrobial activity, macrolides possess immunomodulatory properties that may confer beneficial effects to patients with respiratory diseases associated with chronic inflammation . These properties include attenuation of inflammatory responses in the lung, mucoregulatory properties, and effects on bronchial responsiveness . Macrolides increase mucociliary clearance, improve sinusitis symptoms, and decrease nasal secretions and polyp size in patients with sinusitis . They also have been shown to modify the inflammatory response associated with chronic sinusitis . In patients with asthma, macrolides have been reported to reduce airway hyperresponsiveness and improve pulmonary function, and have historically been selected for their "steroid-sparing" effect . Preliminary data from studies of patients with COPD have shown improvements in symptom scores and FEV(1) after macrolide treatment . As biological response modifiers, macrolides have the potential to improve the outcomes of patients with inflammatory airway diseases . Large scale, placebo-controlled clinical trials designed to assess long-term efficacy and safety in these diseases are warranted. Int Endod J, 2004 Feb, 37(2), 91 - 104 The use of glass ionomer cements in both conventional and surgical endodontics; De Bruyne MA et al.; The capacity to bond to dental tissues, especially to dentine, their long-term fluoride release and their biocompatibility make glass ionomer cements (GICs) advantageous for use in endodontics, as well as in restorative dentistry . This review provides information on the basic properties of GICs, such as adhesion, antimicrobial effects and biocompatibility, particularly as they relate to use in endodontics . Indications for the use of GICs in endodontics are orthograde root canal sealing, root-end filling, repair of perforations and root resorption defects, treatment of vertical fractures and maintenance of the coronal seal . The paper includes a review on each of these indications . It is concluded that in spite of the critical handling characteristics and the inconclusive findings regarding sealing ability and antimicrobial activity, there is substantial evidence to confirm their satisfactory clinical performance . Both soft tissue and bone compatibility make them suitable for use during endodontic surgery. Pediatr Infect Dis J, 2004 Feb, 23(2 Suppl), S108 - 14 Single dose azithromycin for the treatment of uncomplicated otitis media; Arguedas A et al.; Three clinical trials have examined the efficacy and safety of single dose azithromycin (30 mg/kg) in children with uncomplicated acute otitis media (AOM) . In the first trial, a small pilot study, the clinical and microbiologic efficacy of single dose azithromycin was comparable with that of 3-day azithromycin or single dose ceftriaxone . A second, non-comparative trial confirmed the clinical and microbiologic efficacy of the single dose regimen . The third study, a large double blind, double dummy trial, demonstrated comparable clinical success rates between single dose azithromycin and 10-day standard amoxicillin/clavulanate . The incidence of drug-related adverse events in patients treated with single dose azithromycin was low in all three trials and similar to rates that have been reported for other antimicrobial agents used for the treatment of patients with AOM . In the amoxicillin/clavulanate trial, compliance with single dose azithromycin was significantly better than with the amoxicillin/clavulanate regimen (P < 0.001) . We conclude that a single dose of azithromycin (30 mg/kg) is safe and effective for the treatment of uncomplicated AOM in children. Curr Allergy Asthma Rep, 2004 Mar, 4(2), 132 - 8 Antibiotics in asthma; Beuther DA et al.; Asthma pathogenesis appears to be a result of a complex mixture of genetic and environmental influences . There is evidence that Mycoplasma pneumoniae and Chlamydia pneumoniae play a role in promoting airway inflammation that could contribute to the onset and clinical course of asthma . If antimicrobial therapy can eradicate these organisms, it might be possible to alter the course of the disease . Although antibiotics have no role in the routine management of acute exacerbations of asthma, certain macrolide antibiotics have been shown to have anti-inflammatory activity . Part of this effect is due to their known inhibition of steroid and theophylline metabolism, but through a myriad of mechanisms that are incompletely understood, macrolide antibiotics have additional broad anti-inflammatory properties that might prove useful in the management of asthma and other inflammatory diseases. Acta Pharm, 2003 Mar, 53(1), 1 - 13 Isolation of 4-chloro-3-formyl-2-(2-hydroxyethene-1-yl) quinolines by Vilsmeier Haack reaction on quinaldines: Construction of diazepino quinoline heterocycles and their antimicrobial and cytogenetic studies; Kumar RN et al.; Application of Vilsmeier conditions to 4-hydroxyquinaldines gives 4-chloro-3-formyl-2-(2-hydroxyethene-1-yl)-quinolines as an intermediate . The latter is utilized to prepare diazepino quinolines on treatment with phenylhydrazine hydrochloride . All the synthesized compounds have been screened for their antibacterial and antifungal as well as cytogenetic activities. Acta Pharm, 2003 Sep, 53(3), 213 - 21 Studies on thiazolopyridines--a novel synthesis of bis-thiazolopyridines as promising antimicrobial agents; Azab ME et al.; A variety of novel bis-thiazolopyridine derivatives 4a-e were synthesized via the reaction of bis-thiazolinone 3 with different arylcinnamonitrile derivatives (1:2 molar ratio), whereas the reaction of bis-compounds 7a-e with malononitrile in ethanol solution containing a few drops of piperidine afforded the novel bis-thiazolopyridines 8a-e . The structures of the synthesized compounds were established by elemental analyses and spectral data . Some of the newly synthesized compounds show moderate to high antimicrobial activity. Acta Pharm, 2003 Dec, 53(4), 287 - 94 A one pot synthesis and evaluation of 13-oxo-quino{3,4-b}carbazol-N-oxides as antimicrobial agents; Danish IA et al.; 1-Oxo-1,2,3,4-tetrahydrocarbazoles (1a-e) upon mixed aldol condensation with o-nitrobenzaldehyde (2) yielded 13-oxo-quino{3,4-b}carbazol-N-oxides (3a-e) . All the prepared compounds were characterized by elemental and spectral analysis . A plausible mechanism for the formation of the final products is proposed . The title compounds proved to have great potentialities as antibacterial and antifungal agents due to the presence of the N-oxide group . Particularly, the chloro substituted derivative, 3d, showed excellent antimicrobial activity. Zhonghua Yan Ke Za Zhi, 2003 Dec, 39(12), 736 - 9 {Aqueous humor penetration of topically applied ofloxacin, ciprofloxacin and tobramycin}; Yao K et al.; OBJECTIVE: To compare the aqueous humor penetration of topically applied ofloxacin, ciprofloxacin and tobramycin in human eyes . METHODS: Senile cataract patients (125 eyes in 125 cases) receiving phacoemulsification were randomized into three groups: ofloxacin, 42 eyes; ciprofloxacin, 41 eyes and tobramycin, 41 eyes . Each group was randomized into five sub-groups, with 8 or 9 eyes in each sub-group . Each group received either 0.3% ofloxacin, ciprofloxacin or tobramycin topical drops preoperatively . Eyedrops were instilled one drop every 15 minutes for six times . Aqueous samples were obtained from different sub-groups during surgery, 7.5, 15.0, 30.0, 60.0 and 120.0 min after the last drop, respectively . Concentration of the antimicrobial agents was determined by the HPLC (high pressure liquid chromatography) . RESULTS: Aqueous humor concentration of ofloxacin was significantly higher than that of ciprofloxacin at the same period after the last drop . The bioavailability of ofloxacin was 6 times that of ciprofloxacin . Tobramycin could not be detected by HPLC, so its concentration was lower than the minimum detectable level by HPLC (0.05 micro g/ml) . CONCLUSION: Ofloxacin has the best aqueous penetration in human eyes, as compared with ciprofloxacin and tobramycin, which suggests ofloxacin could be the preferred topical medicine for the prevention and treatment of endophthalmitis. Cent Eur J Public Health, 2003 Dec, 11(4), 229 - 37 Mathematical models for the evaluation of antibiotic resistance in hospitals: a systematic review; Bonovas S et al.; As the appearance and spread of antibiotic resistance is becoming an increasingly serious public health problem, there is a definite need for further studies by simulation, experiment and observation . Mathematical models may provide very useful tools to develop a rationale to extend the effective life of existing and newly introduced antimicrobial agents . In this work we systematically reviewed a number of mathematical models recently presented in the literature, in order to provide a brief and informative tool for public health policy makers, regarding the spread of antibiotic resistance, worldwide. Neth J Med, 2003 Nov, 61(11), 341 - 2 Mapping antibiotic use and resistance in the Netherlands: SWAB and NethMap; Verbrugh HA; The worldwide emergence of antimicrobial resistance has elicited responses from national and international organisations, including the World Health Organisation and the European Union . In the Netherlands, the non-profit foundation SWAB was jointly started by several professional medical societies to coordinate the Dutch efforts in preventing and reversing the trend of emerging resistance . SWAB publishes guidelines on the prudent use of antibiotics in this and other journals . The results of SWAB's surveillance systems for antibiotic consumption and resistance were recently summarised in its NethMap 2003 document . Attention should now be focused on elucidating the major determinants of antibiotic use and resistance emergence, and designing effective intervention strategies to reverse the trend of resistance emergence. Kurume Med J, 2003, 50(3-4), 99 - 107 Interactions of a small linear cationic peptide with lipopolysaccharide and lipoteichoic acid; Hamamoto K et al.; Cationic peptides are known to play critical roles in innate immunity . The peptides exert not only antimicrobial activity but also suppress the activity of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) by binding to them . We have previously reported that L-peptide, a small linear cationic peptide derived from human granulysin displays broad-spectrum antimicrobial activity . In this study, the in vitro interactions of L-peptide with LPS and LTA were examined . LPS and LTA were found to inhibit the antimicrobial activity of the L-peptide in a dose-dependent manner, and they were shown to bind with the L-peptide . On the other hand, L-peptide failed to inhibit LPS- or LTA-induced cytokine production by macrophages or to block the binding of LPS to the cell surface . Thus, there seems to be a hierarchy that places LPS and LTA above L-peptide in the interactions of L-peptide with LPS and LTA. Veterinary Clin North Am Exot Anim Pract, 2004 Jan, 7(1), 169 - 89, vii Use of potentiated antibiotics in wound management; Ritchie BW et al.; Prevention or resolution of microbial colonization of wounds is critical to rapid and uneventful healing . The use and misuse of antimicrobial agents continues to support the evolution of multidrug resistant organisms that can cause severe or life-threatening infections . Chelating agents have been shown to potentiate the effects of antimicrobial compounds . The third generation chelating agent . Tricide has been shown to be effective against many multidrug resistant pathogens, prevents pathogens from development resistance to the antimicrobials with which it is mixed and substantially reduces the amount of antimicrobials needed to kill bacteria and fungi. AACN Clin Issues, 2004 Jan-Mar, 15(1), 18 - 44 The puzzle of sepsis: fitting the pieces of the inflammatory response with treatment; Cunneen J et al.; Sepsis is a complex syndrome characterized by simultaneous activation of inflammation and coagulation in response to microbial insult . These events manifest as systemic inflammatory response syndrome (SIRS)/sepsis symptoms through release of proinflammatory cytokines, procoagulants, and adhesion molecules from immune cells and/or damaged endothelium.Conventional treatments have focused on source control, antimicrobials, vasopressors, and fluid resuscitation; however, a new treatment paradigm exists: that of treating the host response to infection with adjunct therapies including early goal directed therapy, drotrecogin alfa (activated), and immunonutrition . The multimechanistic drotrecogin alfa (activated) has been shown to reduce mortality in the severely septic patient when combined with traditional treatment . Therapies targeting improved oxygen and blood flow and reduction of apoptosis and free radicals are under investigation . Early sepsis diagnosis through detection of pro calcitonin, C reactive protein, sublingual CO2, and genetic factors may be beneficial . Ultimately, intervention timing may be the most important factor in reducing severe sepsis mortality. J Clin Microbiol, 2004 Feb, 42(2), 909 - 11 Evaluation of Sensititre automated reading and incubation system for automated reading of Sensititre broth microdilution susceptibility plates; Chapin KC et al.; The Sensititre Automated Reading and Incubation System (ARIS) performs automated reading of Sensititre identification and susceptibility plates . ARIS susceptibility results were compared to manually read results . A total of 212 isolates (3352 organism-antimicrobial agent combinations) yielded 99.4% essential agreement and categorical error rates of 0.2% minor, 0% major, and 1.0% very major . ARIS yields accurate susceptibility results compared to plates read manually. J Clin Microbiol, 2004 Feb, 42(2), 734 - 40 Prospective study of use of PCR amplification and sequencing of 16S ribosomal DNA from cerebrospinal fluid for diagnosis of bacterial meningitis in a clinical setting; Schuurman T et al.; We have evaluated the use of a broad-range PCR aimed at the 16S rRNA gene in detecting bacterial meningitis in a clinical setting . To achieve a uniform DNA extraction procedure for both gram-positive and gram-negative organisms, a combination of physical disruption (bead beating) and a silica-guanidiniumthiocyanate procedure was used for nucleic acid preparation . To diminish the risk of contamination as much as possible, we chose to amplify almost the entire 16S rRNA gene . The analytical sensitivity of the assay was approximately 1 x 10(2) to 2 x 10(2) CFU/ml of cerebrospinal fluid (CSF) for both gram-negative and gram-positive bacteria . In a prospective study of 227 CSF samples, broad-range PCR proved to be superior to conventional methods in detecting bacterial meningitis when antimicrobial therapy had already started . Overall, our assay showed a sensitivity of 86%, a specificity of 97%, a positive predictive value of 80%, and a negative predictive value of 98% compared to culture . We are currently adapting the standard procedures in our laboratory for detecting bacterial meningitis; broad-range 16S ribosomal DNA PCR detection is indicated when antimicrobial therapy has already started at time of lumbar puncture or when cultures remain negative, although the suspicion of bacterial meningitis remains. Appl Environ Microbiol, 2004 Feb, 70(2), 752 - 7 Role of calf-adapted Escherichia coli in maintenance of antimicrobial drug resistance in dairy calves; Khachatryan AR et al.; The prevalence of antimicrobial drug-resistant bacteria is typically highest in younger animals, and prevalence is not necessarily related to recent use of antimicrobial drugs . In dairy cattle, we hypothesize that antimicrobial drug-resistant, neonate-adapted bacteria are responsible for the observed high frequencies of resistant Escherichia coli in calves . To explore this issue, we examined the age distribution of antimicrobial drug-resistant E . coli from Holstein cattle at a local dairy and conducted an experiment to determine if low doses of oxytetracycline affected the prevalence of antimicrobial drug-resistant E . coli . Isolates resistant to tetracycline (>4 microg/ml) were more prevalent in <3-month-old calves (79%) compared with lactating cows (14%) . In an experimental trial where calves received diets supplemented with or without oxytetracycline, the prevalence of tetracycline-resistant E . coli was slightly higher for the latter group (P = 0.039), indicating that drug use was not required to maintain a high prevalence of resistant E . coli . The most common resistance pattern among calf E . coli isolates included resistance to streptomycin (>12 microg/ml), sulfadiazine (>512 microg/ml), and tetracycline (>4 microg/ml) (SSuT), and this resistance pattern was most prevalent during the period when calves were on milk diets . To determine if prevalence was a function of differential fitness, we orally inoculated animals with nalidixic acid-resistant strains of SSuT E . coli and susceptible E . coli . Shedding of SSuT E . coli was significantly greater than that of susceptible strains in neonatal calves (P < 0.001), whereas there was no difference in older animals (P = 0.5) . These data support the hypothesis that active selection for traits linked to the SSuT phenotype are responsible for maintaining drug-resistant E . coli in this population of dairy calves. Front Biosci, 2004 Jan 01, 9, 946 - 55 CNS vasculitis; Kelley RE; Vasculitis of the central nervous system can be of several varieties depending upon the vessel(s) involved and type of disorder . One can see primary CNS vasculitis as a distinct entity which is primarily manifested as central nervous system injury in a vascular distribution or the vasculitic process can be secondary to a systemic disorder such as systemic lupus erythematosus (SLE) or polyarteritis nodosa (PAN) . The inflammation of the CNS vessels can be immune mediated or infectious in nature and a number of "triggers" have been identified including hypersensitivity states . It is quite probable that there is a genetic predisposition in certain individuals and this can lead to an enhanced risk of a vasculitic process when there is exposure to a particular antigen that "sets off" the immune system . The potential for response of the process to antimicrobials and/or immunosuppressants, and the potential for devastating consequences if the process is left untreated, has heightened the urgency in recognizing CNS vasculitis . Key to the recognition and treatment of CNS vasculitis is the evolution of newer insights into the pathogenesis . For example, it is evident that most vasculitides are cell-mediated . Antigen stimulation of CD4+T cells is believed to play a crucial role in giant cell (temporal) arteritis which is the most common type of CNS vasculitis . Identification of genetic susceptibility has also contributed to our understanding of the cascade of events that leads to vascular injury on an inflammatory basis. J Dairy Sci, 2004 Jan, 87(1), 191 - 201 Management practices and reported antimicrobial usage on conventional and organic dairy farms; Zwald AG et al.; The primary objective was to compare reported antimicrobial usage between conventional and organic dairy farms . A secondary objective was to contrast selected management characteristics of conventional and organic dairy herds . A questionnaire was administered on site to selected dairy farmers located in Michigan, Minnesota, New York, and Wisconsin . Organic herds (n = 32) were smaller and produced less milk than conventional herds (n = 99) . Lactating cows in organic dairies were more likely to be housed in tie stalls, whereas most conventional dairies housed cows in free stalls and milked in a parlor . Total mixed rations and purchased feeds were used on more conventional dairy farms compared with organic dairy farms . Conventional dairy producers were more likely to use advice from veterinarians for recommendations of treatment, and organic dairy producers were more likely to rely on advice from other farmers . Based on recall of antibiotic usage in the previous 60 d, 5.1, 84.9, 9.1, and 0.9% of farmers with conventional herds reported treatment of none, 1 to 10%, 11 to 25%, and >25% of milk cows, respectively . Most organic farmers (90.6%) reported no antibiotic treatments of milk cows, whereas 9.4% reported treating 1 to 10% of milk cows . Ceftiofur was the most commonly reported antibiotic for both farm types . Milk replacer containing antibiotics was reportedly used on 49.5% of conventional herds but only on one organic herd (3.1%) . Antibiotics were used in heifer calves on 74.7% of conventional herds versus 21.9% of organic herds . Antibiotics to treat mastitis were used on 79.8% of conventional herds but on none of the organic herds . Most organic farms were in compliance with standards in advance of implementation of regulations.
|
© 2005
Transgalactic Ltd (manufacturer of Bioscreen C software) |
Privacy Statement | P.O. Box
1393, 00101 Helsinki, Finland,
Last modified: May 25, 2005
| ||||||
