J Nat Prod, 2004 Jul, 67(7), 1156 - 61 Cytotoxic and antimicrobial constituents of the bark of Diospyros maritima collected in two geographical locations in Indonesia; Gu JQ et al.; Bioactivity-directed fractionation of extracts of two Diospyros maritima bark samples from Indonesia,one collected at sea level in a beach forest in Java and the other collected at a slight elevation away from the sea shore on the island of Lombok, yielded a diverse set of secondary metabolites . The naphthoquinone plumbagin (1), although found in extracts of both specimens, constituted a much larger percentage of the former sample, which also yielded a series of plumbagin dimers, maritinone (2), chitranone (3), and zeylanone (4) . The latter sample yielded a new naphthoquinone derivative, (4S)-shinanolone (5), and a new natural product coumarin, 7,8-dimethoxy-6-hydroxycoumarin (6), along with three other analogues of plumbagin, 2-methoxy-7-methyljuglone (7), 3-methoxy-7-methyljuglone (8), and 7-methyljuglone (9) . The structures of compounds 5 and 6 were elaborated by physical, spectral, and chemical methods . All of the isolates were evaluated in both cytotoxicity and antimicrobial assays, and structure-activity relationships of these naphthoquinones are proposed . Plumbagin (1) and maritinone (2) were evaluated also for in vivo antitumor activity in the hollow fiber assay, but both were found to be inactive. J Food Prot, 2004 Jul, 67(7), 1501 - 6 Control of Escherichia coli O157:H7 with sodium metasilicate; Weber GH et al.; Three intervention strategies-trisodium phosphate, lactic acid, and sodium metasilicate--were examined for their in vitro antimicrobial activities in water at room temperature against a three-strain cocktail of Escherichia coli O157:H7 and a three-strain cocktail of "generic" E . coli . Both initial inhibition and recovery of injured cells were monitored . When 3.0% (wt/wt) lactic acid, pH 2.4, was inoculated with E . coli O157:H7 (approximately 6 log CFU/ml), viable microorganisms were recovered after a 20-min exposure to the acid . After 20 min in 1.0% (wt/wt) trisodium phosphate, pH 12.0, no viable E . coli O157:H7 microorganisms were detected . Exposure of E . coli O157:H7 to sodium metasilicate (5 to 10 s) at concentrations as low as 0.6%, pH 12.1, resulted in 100% inhibition with no recoverable E . coli O157:H7 . No difference in inhibition profiles was detected between the E . coli O157:H7 and generic strains, suggesting that nonpathogenic strains may be used for in-plant sodium metasilicate studies. Pharmacoepidemiol Drug Saf, 2004 Jul, 13(7), 465 - 71 Use of antibiotics at hospitals in Stockholm: a benchmarking project using internet; Bergman U et al.; PURPOSE: To evaluate the internet way of feedback to prescribing physicians, providing data on antimicrobial use and to assess the applicability of the DU90% (i.e . Drug Utilisation 90%--the number of drugs accounting for 90% of the volume of usage in defined daily doses, (DDDs)) methodology in the hospital setting . METHODS: Antimicrobial drug use was evaluated in all major departments in seven hospitals in Stockholm in the year 2000 . All data were presented anonymously on Aggregate data on antimicrobial drug use were expressed as the number of DDDs and costs per 100 bed-days . We focused on the number of drugs accounting for 90% of the volume (DDD), including the level of adherence to guidelines . The chief physicians assessed this feedback by a questionnaire . RESULTS: The number of DDDs/100 bed-days varied among different clinics and ranged from 39 to 57 (internal medicine) to 102 to 161 (infectious disease) . The cost per 100 bed-days varied more than two-fold . The number of different antibiotics within the DU90% segment ranged from 9 to 13 (orthopaedic clinics) to 16 to 23 (infectious disease) . According to the questionnaire, data were considered to be clearly presented and physicians would like to receive this kind of reports in the future, not only for antibiotics but also for other drugs . CONCLUSION: Presenting physicians with aggregate data on drug use via internet could provide a stimulus for prescribing improvement. J Antimicrob Chemother, 2004 Aug, 54(2), 566 - 9 Epub 2004 Jul 21. Combination therapy with polymyxin B for the treatment of multidrug-resistant Gram-negative respiratory tract infections; Sobieszczyk ME et al.; BACKGROUND: The treatment of infections caused by multidrug-resistant (MDR) Gram-negative organisms poses a therapeutic challenge . The use of polymyxin B has been resurrected specifically for this purpose . PATIENTS AND METHODS: We retrospectively reviewed the clinical and microbiological efficacy, and safety profile of polymyxin B in the treatment of MDR Gram-negative bacterial infections of the respiratory tract . Twenty-five critically ill patients received a total of 29 courses of polymyxin B administered in combination with another antimicrobial agent . RESULTS: Patients were treated with intravenous, and/or aerosolized polymyxin B . Mean duration of polymyxin B therapy was 19 days (range 2-57 days) . End of treatment mortality was 21%, and overall mortality at discharge was 48% . Nephrotoxicity was observed in three patients (10%) and did not result in discontinuation of therapy . CONCLUSIONS: Polymyxin B in combination with other antimicrobials can be considered a reasonable and safe treatment option for MDR Gram-negative respiratory tract infections in the setting of limited therapeutic options. FEMS Microbiol Lett, 2004 Aug 1, 237(1), 41 - 7 Phenazine-1-carboxylic acid is negatively regulated and pyoluteorin positively regulated by gacA in Pseudomonas sp . M18; Ge Y et al.; The biosynthesis of antimicrobial metabolites is controlled by the GacS/GacA two-component regulatory system in Pseudomonas species . The production of phenazine-1-carboxylic acid and pyoluteorin is differentially regulated by GacA in Pseudomonas sp . M18 . Pyoluteorin was reduced to nondetectable level in culture of the gacA insertional mutant strain M18G grown in King's medium B broth, whereas phenazine-1-carboxylic acid production was increased 30-fold over that of the wild-type strain . Production of both antibiotics was restored to wild-type levels after complementation in trans with the wild-type gacA gene . Expression of the translational fusions phzA'-'lacZ and pltA'-'lacZ confirmed the effect of GacA on both biosynthetic operons. MedGenMed . 2004 May 11;6(2):1. A survey on current attitude of practicing physicians upon usage of antimicrobial agents in southern part of India; Sivagnanam G et al.; CONTEXT: Antimicrobial resistance is a serious public health concern worldwide . Inappropriate prescribing, including the wrong drug, incorrect dose/duration, and poor compliance, contributes to it . OBJECTIVE: To identify factors determining the attitudes and practices of prescribers regarding antibiotic usage and to suggest measures that contain antibiotic resistance . DESIGN AND SETTING: With a convenient sample, general practitioners and specialists of both sexes from 5 districts of Tamilnadu state, India, were approached for the study . A slightly modified, self-administered, anonymous questionnaire of the Alliance for the Prudent Use of Antibiotics was used . The deciding factors to prescribe an antibiotic and the reasons for the attitude to prescribe a broad-spectrum antibiotic were elicited . RESULTS: Out of the 285 participants 120, 110, and 47 practiced at city, semiurban, and rural areas, respectively . The responses were graded with a total possible score of 150 . There was no significant difference between men and women or between specialist and nonspecialists in scores . The majority believed that antibiotics are overprescribed . Purulent discharge (65%), antibiotic-resistance concerns (48%), fever (40%), and patient satisfaction (29%) were the strong influences to prescribe an antibiotic . Similar reasons were cited for the belief of prescribing a broad-spectrum antibiotic . The 3 most commonly prescribed antimicrobials were amoxicillin (21%), ciprofloxacin (18%), and co-trimoxazole (11%) . About 42% used an antibiogram only to the extent of less than 10% . CONCLUSION: Patient requests/expectations, patient satisfaction, purulent discharge, and fever strongly pressurized practitioners to prescribe antibiotics . Patient and time pressures, diagnostic and treatment uncertainties, and the poor utilization and/or ill-affordable antibiogram facility all point to an urgent, multidimensional approach to contain antibiotic resistance. Int J Pharm, 2004 Aug 6, 280(1-2), 173 - 83 Antimicrobial activity of polyurethanes coated with antibiotics: a new approach to the realization of medical devices exempt from microbial colonization; Piozzi A et al.; Intravascular devices are widely used for vascular access but are associated with substantial risk of development of devices-related bloodstream infection (DR-BSI), which causes a considerable increase of morbidity and mortality, prolonged hospitalisation and growing medical costs . Since conventional treatment of DR-BSI fails in a significant number of cases, resulting in removal of the device, new approaches are needed to prevent bacterial colonization . In this paper, two antibiotics, rifampin and amoxicillin, have been adsorbed on polyurethanes exhibiting acidic or basic properties . The influence of the type of antibiotic-polymer interaction on the amount of adsorbed antibiotic and on the release kinetics was studied . It was seen that the antibiotic-polymer affinity increases both with the introduction in the polymer side-chain of functional groups and with the matrix hydrophilicity . The antimicrobial activity of the treated polymers, evaluated in vitro by the Kirby-Bauer test, depends on the amount of antibiotic adsorbed, on the strength of drug-matrix interaction and on the water swelling of the polymers . The inhibition zone of bacterial growth lasts only a few hours for the amoxi-coated polymers while remains at least for five months for the rifampin-coated ones . The presence of serum proteins decreases by about 30% the inhibition zone diameter of these latest matrices after two months. Curr Infect Dis Rep, 2004 Aug, 6(4), 298 - 304 Central Nervous System Lyme Disease; Halperin JJ; Nervous system infection with Borrelia burgdorferi frequently causes meningitis and rarely causes encephalomyelitis . Altered cognitive function also can occur in the absence of central nervous system infection . Recently developed serodiagnostic tools, such as the C6 assay, and appropriate use of Western blotting, promise to improve diagnostic accuracy . Treatment trials have demonstrated the efficacy of relatively brief courses of oral antimicrobial agents, even in peripheral nervous system infection and meningitis . Several well-performed studies have clearly shown that prolonged antimicrobial treatment of "post-Lyme disease" is ineffective . Diagnosis and treatment of Lyme disease continue to improve. Curr Infect Dis Rep, 2004 Aug, 6(4), 270 - 275 Molecular Methods in the Diagnosis of Endocarditis; Anguita-Alonso P et al.; Advances in molecular microbiologic diagnostics have yielded new tools to diagnose infective endocarditis . These tools can detect microorganisms that are difficult to grow or are uncultivable, because of prior antimicrobial therapy or because of innate characteristics of the microorganisms . This paper reviews molecular microbiologic diagnostic techniques and their role in the diagnosis of infective endocarditis. Zhonghua Er Ke Za Zhi, 2004 Jun, 42(6), 417 - 20 {Long-term therapeutic effect of triple therapy consisted of omeperazole, clarithromycin and amoxycillin in children with Helicobacter pylori infection and approach to re-treatment after failure of the treatment}; Chen XX et al.; OBJECTIVE: Helicobacter pylori (Hp) infection presents high prevalence in the world, but there are few pediatric assays evaluating antimicrobial treatment using a short regimen of triple therapy . To evaluate the eradication rate and long term therapeutic effect of a triple therapy consisted of omeperazole, clarithromycin (CLA) and amoxycillin (AMO) on Hp infection, the authors explored the alternative therapeutic programs and their effects after first therapeutic failure . METHODS: A total of 192 children with Hp infection were divided into two groups: 157 children were given the triple therapy for one week (CLA group); 35 children were given another triple therapy composed of omeperazole, metronidazole (MET) and AMO for two weeks (MET group) . All of the children were followed up for 1 - 36 months after the therapies ended . Twenty-two children in whom Hp was eradicated with CLA triple therapy were followed up for 3 years . The children of the two groups who had therapeutic failure were given re-treatment as follows . CLA triple therapy was given for one week to the children who had failure after MET triple therapy; increased doses of CLA with longer treatment course was given to the children who had failure after CLA triple therapy . A tetra therapy consisted of omeperazole, colloidal bismuth subcitrate (CBS), furazolidone (FUR) and AMO was given to the children in whom the re-treatment failed . RESULTS: The Hp eradication and ulcer recovery rate of CLA group was 90.4% (142/157) and 96.9% (32/33), respectively; the Hp eradication rate of MET group was 77% (27/35) . There was significant difference between eradication rates of the two groups (chi(2) = 4.69, P < 0.05) . The recurrence rate of 22 Hp eradicated children treated with CLA triple therapy was 4.5% (1/22) during the 3-year follow-up . The eradication rate of the three re-treatment programs for 29 children was 75% (6/8), 77% (11/15) and 100% (6/6), respectively . CONCLUSION: (1) Omeperazole, CLA and AMO triple therapy for one week was the best to eradicate Hp infection with high eradication rate, few side effects, short period of treatment, good compliance and low recurrence rate . (2) Proper increase of CLA dose and longer therapeutic course may increase the eradication rate . Omeperazole, CBA, FUR and AMO tetra therapeutic program may be used as an alternative treatment in patients who develop resistance to CLA triple therapy. BMC Genomics . 2004 Jul 20;5(1):48. Characterization of the GATC regulatory network in E . coli; Riva A et al.; BACKGROUND: The tetranucleotide GATC is methylated in Escherichia . coli by the DNA methyltransferase (Dam) and is known to be implicated in numerous cellular processes . Mutants lacking Dam are characterized by a pleiotropic phenotype . The existence of a GATC regulated network, thought to be involved in cold and oxygen shift, had been proposed and its existence has recently been confirmed . The aim of this article is to describe the components of the GATC regulated network of E . coli in detail and propose a role of this network in the light of an evolutionary advantage for the organism . RESULTS: We have classified the genes of the GATC network according to the EcoCyc functional classes . Comparisons with all of E . coli's genes and the genes involved in the SOS and stress response show that the GATC network forms a group apart . The functional classes that characterize the network are the Energy metabolism (in particular respiration), Fatty acid/ Phospholipid metabolism and Nucleotide metabolism . CONCLUSIONS: The network is thought to come into play when the cell undergoes coldshock and is likely to enter stationary phase.The respiration is almost completely under GATC control and according to our hypothesis it will be blocked at the moment of coldshock; this might give the cell a selective advantage as it increases its chances for survival when entering stationary phase under coldshock . We predict the accumulation of formate and possibly succinate, which might increase the cell's resistance, in this case to antimicrobial agents, when entering stationary phase. Angle Orthod, 2004 Jun, 74(3), 414 - 9 Effectiveness of a hydrophilic primer when different antimicrobial agents are mixed; Karaman AI et al.; The purpose of this study was to determine whether different types of antimicrobial agents with hydrophilic primer applied to etched enamel surfaces will affect the shear bond strength (SBS) and the bracket/adhesive failure modes of metallic orthodontic brackets . Eighty noncarious human premolars were divided into four groups of 20 each . A composite resin (Transbond XT) was used to bond stainless steel brackets . Teeth in the first group were used as a control and bonded with standard procedures . For the other three groups, mixtures containing a hydrophilic primer (Transbond MIP) and one of three anti-microbial agents were prepared (Cervitec: in 1:2 ratio; chlorhexidine mouthwash and EC40 varnish in 1:1 ratio) . These mixtures were applied to the etched enamel surfaces and thoroughly light cured for 20 seconds, and the brackets were bonded and light cured for 40 seconds . The SBS values of these brackets (Mpa) were recorded using a universal testing machine . Adhesive Remnant Index scores were determined after failure of the brackets . Data were analyzed using analysis of variance (ANOVA), Tukey honestly significant difference, and chi-square tests . Results of ANOVA revealed statistically significant differences in bond strengths among the various groups tested (P < .05) . The bond strength values in these four groups compared favorably with those from other studies and the minimal bond strength values that are clinically acceptable . However, results of this study demonstrated that groups 1 (control) and 2 (Cervitec varnish) had higher SBS values than the other applications . Application of different antimicrobial agents may result in differences in the site of failure. Farmaco, 2004 Aug, 59(8), 637 - 44 Synthesis and antiproliferative activity of 3-aryl-2-{1H(2H)-benzotriazol-1(2)-yl}acrylonitriles variously substituted: Part 4; Carta A et al.; A new series of variously substituted 3-aryl-2-{1H(2H)-benzotriazol-1(2)-yl}acrylonitriles was synthesized and tested for antiproliferative and antitubercular activity as part of our continuing research program in the antimicrobial and antitumor fields . The most cytotoxic derivatives (5a,g,i,j,l and 7b) (CC50 < 3.0 microM against MT-4 cells) were evaluated against a panel of human cell lines derived from hematological and solid tumors, using 6-mercaptopurine (6-MP) and etoposide as reference drugs . In particular, E-2-(5,6-dimethyl-1H-benzotriazol-1-yl)-3-(3-nitrophenyl)acrylonitrile (5g) resulted more potent than 6-MP on all cell lines, even if 2-14-fold less potent than etoposide . In the antitubercular screening, the derivatives 5i,j and 7e showed moderate activity against some resistant strains of Mycobacterium tested. J Ethnopharmacol, 2004 Sep, 94(1), 49 - 54 Effective medicinal plants against enterohaemorrhagic Escherichia coli O157:H7; Voravuthikunchai S et al.; The stimulating effect of subinhibitory concentrations of antibiotics on the production of verocytotoxin (VT) by enterohaemorrhagic Escherichia coli (EHEC) O157:H7 has been claimed . The purpose of this study was to find an alternative, but bioactive medicine for the treatment of this organism . Fifty-eight preparations of aqueous and ethanolic extracts of 38 medicinal plant species commonly used in Thailand to cure gastrointestinal infections were tested for their antibacterial activity against different strains of Escherichia coli, including 6 strains of Escherichia coli O157:H7, Escherichia coli O26:H11, Escherichia coli O111:NM, Escherichia coli O22; 5 strains of Escherichia coli isolated from bovine; and Escherichia coli ATCC 25922 . Inhibition of growth was primarily tested by the paper disc agar diffusion method . Among the medicinal plants tested, only 8 species (21.05%) exhibited antimicrobial activity against Escherichia coli O157:H7 . Acacia catechu, Holarrhena antidysenterica, Peltophorum pterocarpum, Psidium guajava, Punica granatum, Quercus infectoria, Uncaria gambir, and Walsura robusta demonstrated antibacterial activity with inhibition zones ranging from 7 to 17 mm . The greatest inhibition zone against Escherichia coli O157:H7 (RIMD 05091083) was produced from the ethanolic extract of Quercus infectoria . Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined by the agar microdilution method and agar dilution method in petri dishes with millipore filter . Both aqueous and ethanolic extracts of Quercus infectoria and aqueous extract of Punica granatum were highly effective against Escherichia coli O157:H7 with the best MIC and MBC values of 0.09, 0.78, and 0.19, 0.39 mg/ml, respectively . These plant species may provide alternative but bioactive medicines for the treatment of Escherichia coli O157:H7 infection. Fitoterapia, 2004 Jul, 75(5), 514 - 9 Antimicrobial activity of extracts and some compounds from Calea platylepis; do Nascimento AM et al.; The antimicrobial activity of dichloromethane extracts (leaves, flowers and underground parts) and some compounds isolated from Calea platylepis were evaluated by the well diffusion method. Bioorg Med Chem Lett, 2004 Aug 16, 14(16), 4185 - 90 Synthesis and QSAR studies of pyrimido{4,5-d}pyrimidine-2,5-dione derivatives as potential antimicrobial agents; Sharma P et al.; A number of pyrimido{4,5-d}pyrimidine-2,5-dione derivatives were synthesized and screened for antibacterial and antifungal activities . All the synthesized compounds showed the potent antimicrobial activity . The quantitative structure-activity relationship investigation was applied to find a correlation between the different physicochemical parameters of the compounds studied and their biological activity. Colloids Surf B Biointerfaces, 2004 Jun 1, 35(3-4), 235 - 42 A synthetic alternative to natural lecithins with antimicrobial properties; Perez L et al.; Two soft biocompatible cationic surfactants from the amino acid arginine, 1,2-dilauroyl-3-acetylarginyl-rac-glycerol (1212RAc) and 1,2-dimirystoyl-3-acetylarginyl-rac-glycerol (1414RAc), were prepared . Their physicochemical properties show that they can be classified as multifunctional surfactants with self-aggregation behaviour comparable to that of short-chain lecithins . The two surfactants can simultaneously stabilise water-in-oil (W/O) droplets and oil-in-water (O/W) droplets, forming multiple emulsions . They have antimicrobial activity similar to that of conventional cationic surfactants and are as harmless as amphoteric betaines . These surfactants constitute an interesting alternative to the diglycerides and lecithins in formulations that require antimicrobial properties. Wound Repair Regen, 2004 Jul-Aug, 12(4), 439 - 43 Human beta-defensin-2 expression is increased in chronic wounds; Butmarc J et al.; First identified in psoriatic epidermis and subsequently in other inflammatory cutaneous lesions, human beta-defensin-2 (hbetaD-2) is one of two endogenous antimicrobial peptides related to defensins in plants and animals . Our objective was to determine the expression of hbetaD-2 after injury and in chronic wounds . Biopsies of normal ipsilateral thigh skin and wound edges were taken from nine consecutive patients with venous leg ulcers (day 1) and from the same biopsy sites 2 days later (day 3) . Sequential samples were also obtained from intact or meshed bilayered bioengineered skin consisting of neonatal human keratinocytes and dermal fibroblasts in a collagen matrix . Specimens were processed and immunostained for hbetaD-2 using a polyclonal rabbit antibody . In both human tissues and bioengineered skin, staining for hbetaD-2 was confined to the upper epidermal layers, sparing the basal cells . Analysis of 26 tissue samples from patients showed that normal skin had no hbetaD-2 expression but that marked up-regulation occurred after wounding by day 3 . Conversely, chronic ulcers showed moderate-to-strong immunostaining for hbetaD-2 at baseline on day 1, with little or no change in intensity after wounding by day 3 . In vitro, bioengineered skin showed increased distribution of cytoplasmic hbetaD-2 immunostaining after meshing . We conclude that the expression of hbetaD-2 is up-regulated after injury . Chronic wounds uniformly show a constitutively high baseline expression of hbetaD-2, possibly due to ongoing tissue injury and bacterial colonization. Biochemistry, 2004 Jul 27, 43(29), 9527 - 35 Antimicrobial 14-helical beta-peptides: potent bilayer disrupting agents; Epand RF et al.; The interactions of two amphiphilic and cationic, nine-residue beta-peptides with liposomal membranes were studied . These beta-peptides are shown to form 14-helices in the presence of bilayers . Membrane binding and membrane permeabilization occur preferentially in the presence of anionic lipids . The beta-peptides have the ability to cause tranbilayer diffusion of phospholipids, form pores, and promote lipid mixing between liposomes . These beta-peptides have previously been shown to display antimicrobial activity comparable to that of a longer beta-peptide, beta-17, which adopts a different type of helical conformation (12-helix), and to the 23 amino acid (Ala(8,13,18))-magainin-II-amide, which adopts an alpha-helical conformation . In addition, these 14-helical beta-peptides show relatively low hemolytic activity . The biological potency and microbial specificity of the 14-helical beta-peptides, despite their relatively short length, suggests that 14-helices can be particularly disruptive to microbial membranes. Acta Pol Pharm, 2004 Jan-Feb, 61(1), 69 - 74 The quantitative determination of phenolic acids and antimicrobial activity of Symphoricarpos albus (L.) Blake; Szaufer-Hajdrych M et al.; The content of phenolic acids was determined in the extracts and fractions from leaves, flowers and fruits of Symphoricarpos albus (L.) Blake (Caprifoliaceae) by the Arnov's method . Antimicrobial activity of all extracts against Gram-positive anti Gram-negative microorganisms has been tested. Acta Vet Scand Suppl, 2003, 98, 65 - 70 Medication of production animals--cure of malfunctioning animals or production systems? Chriel M, Dietz HH. Medication is used in all intensive animal productions . However, the increasing problems with resistant bacteria in all animal productions and in humans are supported by a number of reports . Special attention is given to the risk for transmitting food-borne (multi) resistant zoonotic agents to humans due to failure in antibiotic treatment resulting in lower cure rates or higher case fatality rates . The use of medication in humans per se is capable of selecting for resistance in human pathogens . Nevertheless, the amount of used medication/antimicrobials in treatment of Danish production animals goes far beyond the amount used for human consumption . The increase in consumption has not been followed by a similarly increased mortality, e.g . illustrated by the number of rendered animals, increased use of injection medicine for veterinary treatments of diseased animals, or increased number of remarks on the carcasses from the slaughterhouses . Medication in animal production is facing its limits and relevant economic alternatives have to be developed . The strategy for the future must concentrate on using medication only for clinically diseased animals and not as a strategic treatment of the whole herd in order to maximise growth and camouflage of suboptimal production systems and insufficient management. Am Fam Physician, 2004 Jul 1, 70(1), 107 - 14 Evaluation and management of nonulcer dyspepsia; Dickerson LM et al.; When no organic cause for dyspepsia is found, the condition generally is considered to be functional, or idiopathic . Nonulcer dyspepsia can cause a variety of symptoms, including abdominal pain, bloating, nausea, and vomiting . Many patients with nonulcer dyspepsia have multiple somatic complaints, as well as symptoms of anxiety and depression . Extensive diagnostic testing is not recommended, except in patients with serious risk factors such as dysphagia, protracted vomiting, anorexia, melena, anemia, or a palpable mass . In these patients, endoscopy should be considered to exclude gastroesophageal reflux disease, peptic or duodenal ulcer, and gastric cancer . In patients without risk factors, consideration should be given to empiric therapy with a prokinetic agent (e.g., metoclopramide), an acid suppressant (histamine-H2 receptor antagonist), or an antimicrobial agent with activity against Helicobacter pylori . Treatment of patients with H . pylori infection and nonulcer dyspepsia (rather than peptic ulcer) is controversial and should be undertaken only when the pathogen has been identified . Psychotropic agents should be used in patients with comorbid anxiety or depression . Treatment of nonulcer dyspepsia can be challenging because of the need to balance medical management strategies with treatments for psychologic or functional disease. World J Gastroenterol, 2004 Aug 1, 10(15), 2281 - 3 Empirical antibiotic treatment with piperacillin-tazobactam in patients with microbiologically-documented biliary tract infections; Bassotti G et al.; AIM: To report our experience with empiric antimicrobial monotherapy (piperacillin/tazobactam, of which no data are available in such specific circumstances) in microbiologically-documented infections in patients with benign and malignant conditions of the biliary tract . METHODS: Twenty-three patients, 10 with benign and 13 with malignant conditions affecting the biliary tree and microbiologically-documented infections were recruited and the efficacy of empirical antibiotic therapy was assessed . RESULTS: The two groups featured similar demographic and clinical data . Overall, the infective episodes were most due to Gram negative agents, more than 60% of such episodes (mostly in malignant conditions) were preceded by invasive instrumental maneuvers . Empirical antibiotic therapy with a single agent (piperacillin/tazobactam) was effective in more than 80% of cases . No deaths were reported following infections . CONCLUSION: An empiric therapeutic approach with piperacillin/tazobactam is highly effective in biliary tract infections due to benign or malignant conditions. Pneumologie, 2004 Jul, 58(7), 499 - 504 {Inhaled antibiotic therapy in bronchiectasis?}; Kohlhaufl M et al.; Antimicrobial therapy is an important aspect of disease management for patients with bronchiectasis . Delivery of an inhaled antibiotic is an appealing alternative to oral or intravenous administration because the antibiotic is delivered in high concentrations directly to the site of infection, eliminating the need for high systemic concentrations and reducing the risk of systemic toxicity . In recent controlled studies these potential benefits have been assessed in patients with bronchiectasis who became colonized by P . aeruginosa and the results support the use of nebulized antibiotics . In up to one-third of patients P . aeruginosa was eradicated from their sputum by inhaled antibiotic therapy and up to 62 % of patients showed improved medical condition . The further development of new aerosol devices supported by clinical testing will allow effective management of patients with bronchiectasis by an inhalation therapy that minimizes time constraints and drug loss which may improve health status and quality of life. Pancreas, 2004 Aug, 29(2), 110 - 5 Novel insulin-releasing peptides in the skin of Phyllomedusa trinitatis frog include 28 amino acid peptide from dermaseptin BIV precursor; Marenah L et al.; OBJECTIVE: The granular glands of amphibians have long been known to produce many biologically active compounds . The aim of this study was to isolate and characterize insulinotropic peptides from the skin of Phyllomedusa trinitatis frog . METHODS AND RESULTS: Crude secretions obtained by mild electrical stimulation of the dorsal skin surface were purified by reverse phase HPLC yielding 80 fractions . In acute incubations with glucose-responsive BRIN-BD11 cells, fractions 39-40 (band 1) and fractions 43-46 (band 2) significantly stimulated insulin release by 1.5 to 2.5-fold . Pooled fractions in bands 1 and 2 were rechromatographed to 4 homogeneous peaks, each with insulin-releasing activity . Mass spectrometry analysis was successfully completed for 3 peptides, indicating 2996.4, 3379.9, and 8326.4 Da . The sequence of the 2996.4 Da peptide was determined as ALWKDILKNVGKAAGKAVLNTVTDMVNQ . This 28-amino-acid peptide has 100% homology with the C-terminal of the 75-amino-acid dermaseptin BIV precursor of a family of structurally related antimicrobial peptides in the skin of the Phyllomedusinae subfamily . CONCLUSION: These data demonstrate that the defensive skin secretions of P . trinitatis contain biologically active peptides, which may have mammalian counterparts and merit further investigation as insulin secretagogues. Cell Tissue Bank, 2002, 3(2), 105 - 19 Processing of ovine cardiac valve allografts: 3 . Implantation following antimicrobial treatment and preservation; Neves J et al.; It is known that a satisfactory clinical outcome can follow the implantation of cardiac valve allografts in spite of the loss of living cells in the tissue . If viable cells are not required for long term graft function, then effective disinfection of the tissue might become possible . In an earlier paper in this series we reported that peracetic acid (PAA) is an effective antimicrobial agent for the treatment of valve allografts; it was lethal to the cells but at a concentration of 0.21% had little effect on the mechanical properties or extracellular morphology of the valve leaflets . It was also found that PAA-treatment could be combined with storage in 85% glycerol at 4 degrees C, or cryopreservation with 10% Me(2)SO, without substantial further impairment of microscopic structure or mechanical properties . In this paper we describe the implantation of processed ovine aortic valves in the descending thoracic aorta of sheep . The experimental groups included control untreated valves and valves that had been treated with antibiotics or PAA and either cryopreserved, or stored in 85% glycerol . The recipient sheep showed good clinical appearances until the experiment was terminated at six months . The explanted grafts were examined by standard morphological and mechanical testing methods . The PAA-treated valves were clearly recognisable as valves: the leaflets had fair to medium morphology in both the unpreserved and the cryopreserved groups . All leaflets had a superficial overgrowth of cells . Microsatellite analysis for allelic differences were performed on samples of donor and recipient tissues using three markers of tissue source . Only one valve, which had been treated with PAA, revealed allelic differences between donor and recipient . It is suggested that DNA-fragments may have remained after the destruction of donor cells and six months of implantation: the overgrowing cells were almost certainly of recipient origin . We conclude that our experiments, in which PAA-treatment was combined with preservation, are sufficiently encouraging to justify further studies to refine the technique, but in our opinion they are not sufficient to justify a clinical trial at this time. Cell Tissue Bank, 2002, 3(2), 91 - 103 Processing of cardiac valve allografts: 2 . Effects of antimicrobial treatment on sterility, structure and mechanical properties; Farrington M et al.; This is the second in a series of papers that report experiments to investigate the properties required for effective tissue valve implants . This paper is concerned with investigations into alternative antimicrobial treatments and the effect these treatments produce on the structural and biomechanical properties of ovine aortic valves . Six treatments were studied: heat, peracetic acid (at two concentrations), chlorine dioxide, a surfactant cleaning agent and a solvent/detergent treatment . Samples of myocardial tissue were exposed to a mixed bacterial culture or one of three virus cultures and then decontaminated . Two of the six treatments (0.35% peracetic acid and heat) were effective in removing both bacterial and viral contamination, reducing levels of contamination by 2.5 to 3 logs, whilst a third (chlorine dioxide) was effective against viruses ( approximately 3 log reduction) . Valves subjected to these treatments were examined by microscopy and measurements of mechanical properties were made . All three treatments seriously damaged endothelial cells and leaflet fibroblasts . Heat treatment also damaged connective tissue components (collagen and elastin) but these changes were not seen after chemical treatment . Mechanical testing confirmed severe damage following heat treatment but chemical treatment showed only minor effects on the elasticity of the leaflets and none on extensibility . These minor effects could be mitigated by exposure to a lower dose of peracetic acid and this treatment could be safely combined with cryopreservation or storage in 85% glycerol . Peracetic acid was the preferred disinfection method for use in the subsequent in vivo studies in sheep. Cell Tissue Bank, 2002, 3(2), 79 - 89 Processing of ovine cardiac valve allografts: 1 . Effects of preservation method on structure and mechanical properties; Aidulis D et al.; It is essential to have some method of preservation of allograft valves during the time between procurement and implantation . Cryopreservation is the most commonly-used storage method today but it has the major disadvantage of high cost, and because its aim is to preserve living cells only relatively gentle antimicrobial treatments are used . This study addresses two interrelated questions: Is it necessary to maintain living donor cells in the tissue graft? Can more effective measures be used to reduce the risk of transmission of diseases, especially viral diseases, via human tissue grafts . In this paper, we report an investigation of four preservation methods that could be combined with more effective disinfection: cryopreservation with dimethyl sulphoxide, storage at approximately 4 degrees C in a high concentration of glycerol as used for the preservation of skin, snap-freezing by immersion in liquid nitrogen and vitrification . Snap freezing was mechanically damaging and vitrification proved to be impracticable but two methods, cryopreservation and storage in 85% glycerol, were judged worthy of further study . Cryopreservation was shown to maintain cellular viability and excellent microscopic structure with unchanged mechanical properties . The glycerol-preserved valves did not contain any living cells but the connective tissue matrix and mechanical properties were well preserved . The importance of living cells in allograft valves is uncertain . If living cells are unimportant then either method could be combined with more effective disinfection methods: in that case the simplicity and economy of the glycerol method would be advantageous . These questions are addressed in the two later papers in this series. Proc R Soc Lond B Biol Sci, 2004 Apr 22, 271(1541), 785 - 8 Interference competition and parasite virulence; Massey RC et al.; Within-host competition between parasites, a consequence of infection by multiple strains, is predicted to favour rapid host exploitation and greater damage to hosts (virulence) . However, the inclusion of biological variables can drastically change this relationship . For example, if competing parasite strains produce toxins that kill each other (interference competition), their growth rates and virulence may be reduced relative to single-strain infections . Bacteriocins are antimicrobial toxins produced by bacteria that target closely related strains and species, and to which the producing strain is immune . We investigated competition between bacteriocin-producing, insect-killing bacteria (Photorhabdus and Xenorhabdus) and how this competition affected virulence in caterpillars . Where one strain could kill the other, and not vice versa, the non-killing strain was competitively excluded, and insect mortality was the same as that of the killing strain alone . However, when caterpillars were multiply infected by strains that could kill each other, we did not observe competitive exclusion and their virulence was less than single-strain infections . The ubiquity and diversity of bacteriocins among pathogenic bacteria suggest mixed infections will be, on average, less virulent than single infections. Altern Med Rev, 2004 Jun, 9(2), 136 - 156 Therapeutic applications of whey protein; Marshall K; Whey, a protein complex derived from milk, is being touted as a functional food with a number of health benefits . The biological components of whey, including lactoferrin, beta-lactoglobulin, alpha-lactalbumin, glycomacropeptide, and immunoglobulins, demonstrate a range of immune-enhancing properties . In addition, whey has the ability to act as an antioxidant, antihypertensive, antitumor, hypolipidemic, antiviral, antibacterial, and chelating agent . The primary mechanism by which whey is thought to exert its effects is by intracellular conversion of the amino acid cysteine to glutathione, a potent intracellular antioxidant . A number of clinical trials have successfully been performed using whey in the treatment of cancer, HIV, hepatitis B, cardiovascular disease, osteoporosis, and as an antimicrobial agent . Whey protein has also exhibited benefit in the arena of exercise performance and enhancement. J Proteome Res, 2004 May-Jun, 3(3), 410 - 6 Proteomic analysis of human tears: defensin expression after ocular surface surgery; Zhou L et al.; Human tear protein profiles were monitored by surface enhanced laser desorption/ionization-time-of-flight mass spectrometry ProteinChip technology (SELDI-TOF ProteinChip) and liquid chromatography-mass spectrometry (LC-MS) . Tears were collected from 21 patients scheduled for surgery to remove an ocular surface neoplasm prior to surgery (day 0) and on days 1, 3, and 30 postoperatively . Using this proteomic approach, we verified that three human alpha-defensins (HNP-1, HNP-2, and HNP-3) were significantly up-regulated in their expression after surgery and that their levels decreased to approximately normal by day 30 by which time healing was complete . Further confirmation of the identity of the alpha-defensins in human tears was made by LC purification, trypsin digestion, and ESI-MS/MS analysis of their tryptic digests . The concentrations of HNP-1 and HNP-2 were determined and shown to be markedly increased after ocular surface surgery . The results of the study suggest that human alpha-defensins HNP-1, HNP-2, and HNP-3 are up-regulated after surgery, and may in addition to their antimicrobial properties have an important role in wound healing. Acta Biochim Biophys Sin (Shanghai), 2004 Apr, 36(4), 297 - 302 Purification of a novel antibacterial short peptide in earthworm Eisenia foetida; Liu YQ et al.; A novel antimicrobial short peptide was purified from earthworm (Eisenia foetida) by a five-step protocol including ammonium sulfate precipitation, ultrafiltration, DE-52 ion exchange chromatography, Sephadex G-10 column chromatography, and C-18 reversed-phase HPLC techniques . The purified peptide was applied to the MALDI-TOP MS to determine the molecular mass and was also subjected to TOF MS-MS analysis to determine the amino acid sequence . As a result, a novel antibacterial peptide, named OEP3121, was obtained, with the molecular mass of 510.8 Da and the sequence being "ACSAG". Chemistry, 2004 Jul 19, 10(14), 3479 - 85 Ionic liquids with symmetrical dialkoxymethyl-substituted imidazolium cations; Pernak J et al.; A new one-step procedure is described for the synthesis of disubstituted imidazolium chlorides . 1,3-Dialkoxymethylimidazolium chlorides thus obtained can be employed as synthetic precursors of symmetrical ILs . The salts have been found to exhibit antimicrobial activity and an antielectrostatic effect . Their densities and viscosities have been determined and are reported herein . It has also been demonstrated that the ILs can be decomposed using an aqueous solution of KMnO(4) . For each IL, the permanganate index (I(Mn)) has been estimated, which varies with the structure of cation . The only limitation of I(Mn) is the degree to which the IL dissolves in water. J Lab Clin Med, 2004 Jul, 144(1), 18 - 26 Azithromycin inhibits interleukin-6 but not fibrinogen production in hepatocytes infected with cytomegalovirus and chlamydia pneumoniae; Bouwman JJ et al.; Chlamydia pneumoniae and cytomegalovirus (CMV) have been associated with the development of atherosclerosis . Inflammatory stimuli initiate the biosynthesis of fibrinogen, interleukin (IL)-6 and plasminogen activator inhibitor (PAI)-1 in the liver . Chronic infection may perpetuate the inflammatory status . We hypothesized that infection of human hepatocytes with the intracellular pathogens C pneumoniae and CMV accelerates biosynthesis of fibrinogen, IL-6, and PAI-1 but that this biosynthesis can be reduced with the use of azithromycin . HepG2 human hepatocytes were infected with C pneumoniae and CMV in vitro in the presence of 0, 0.016, 0.125, or 1 microg/mL azithromycin . We measured IL-6, PAI-1, and fibrinogen after 24, 48, 72, and 96 hours . C pneumoniae-infected hepatocytes produce IL-6 (2667 +/- 309 pg/mL vs 137 +/- 120 pg/mL in uninfected cells after 96 hours . Incubation with 0.016 microg/mL azithromycin decreased IL-6 levels to a mean of 1516 +/- 402 pg/mL, and incubation with 0.125 and 1 microg/mL azithromycin decreased IL-6 to 871 +/- 364 and 752 +/- 403 pg/mL, respectively . C pneumoniae-induced IL-6 production was time- and dose-dependent . The interaction of C pneumoniae with azithromycin treatment was significant, indicating an inhibitory effect of azithromycin on C pneumoniae-induced IL-6 production . CMV infection did not lead to IL-6 production by hepatocytes . C pneumoniae and CMV infection did not induce any changes in PAI-1 production . Fibrinogen production was increased by CMV infection after 72 hours (838 +/- 88 ng/mL; P <.01) and after 96 hours by infection with both C pneumoniae and CMV (765 +/- 100 and 846 +/- 123 ng/mL, respectively; P <.05) . Azithromycin did not suppress CMV- or C pneumoniae-induced fibrinogen production . Moreover, we could not confirm an antiinflammatory effect of azithromycin in experiments with cross-titrations of azithromycin against either IL-1 or IL-6 (P >.05) . Azithromycin reduces C pneumoniae-induced IL-6 production, but not fibrinogen production, by human hepatocytes . This is a result of the antimicrobial properties of azithromycin and not a direct antiinflammatory effect. Ann Pharmacother, 2004 Sep, 38(9), 1400 - 5 Epub 2004 Jul 13. The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data; Basyigit I et al.; BACKGROUND: Clarithromycin is an antimicrobial agent that can be used for treatment of chronic obstructive pulmonary disease (COPD) exacerbations with bronchodilator therapy . However, it has also been shown that clarithromycin has antiinflammatory effects by the inhibition of cytokine production . OBJECTIVE: To evaluate the antiinflammatory effect of clarithromycin on serum and sputum interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and leukotriene B4 levels in patients with COPD . METHODS: Thirty men with mild to moderate COPD were enrolled in this prospective, single-center, double-blind, placebo-controlled study . None of the patients was receiving systemic or inhaled corticosteroids during the study . Subjects received either clarithromycin or placebo for 14 days . Before and after this treatment period, spirometric tests and arterial blood gas analysis were performed, blood was drawn for measurement of serum inflammatory markers, and sputum was induced . RESULTS: There were no statistically significant differences in baseline clinical or laboratory parameters between the groups . After the treatment, the induced sputum total cell counts, and IL-8 and TNF-alpha levels decreased significantly in the clarithromycin group compared with pretreatment levels (mean +/- SD IL-8 1606 +/- 367.3 vs 882 +/- 143.6 pg/mL, p = 0.001; TNF-alpha 638.2 +/- 287.5 vs 390 +/- 235 pg/mL, p = 0.001) . Similarly, decreases in serum inflammatory markers were found in the clarithromycin group while there was no significant change in the placebo group . CONCLUSIONS: This study demonstrated that the decrease in IL-8 and TNF-alpha levels might be related to the antiinflammatory effect of clarithromycin . Thus, we suggest that the use of clarithromycin in COPD exacerbations may either treat the infection or help control the inflammation . Future studies are needed to determine the clinical significance of these findings. Blood, 2004 Nov 1, 104(9), 2947 - 53 Epub 2004 Jul 13. Dual role of phagocytic NADPH oxidase in bacterial killing; Rada BK et al.; The classical model of bacterial killing by phagocytic cells has been recently challenged by questioning the toxic effect of oxygen products and attributing the fundamental role to K(+) ions in releasing antimicrobial proteins within the phagosome . In the present study we followed O(2)(*-) production, changes of membrane potential, K(+) efflux, and bacterial killing in the presence of increasing concentrations of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium . Efficiency of bacterial killing was assessed on the basis of bacterial survival measured by a new semiautomated method . Very low rates of O(2)(*-) production were accompanied by significant membrane depolarization and K(+) release and parallel improvement of bacterial killing . When O(2)(*-) production exceeded 20% of its maximal capacity, no further change was detected in the membrane potential and only minimal further K(+) efflux occurred, yet bacterial survival decreased parallel to the increase of O(2)(*-) production . The presented results indicate that both electrophysiological changes (depolarization and consequent ion movements) and the chemical effect of reactive oxygen species play a significant role in the killing of certain pathogens . The observation that an increase of membrane depolarization can compensate for decreased O(2)(*-) production may be important for potential therapeutic applications. Endocr Pract, 1995, 1(3), 179 - 84 From motilin to motilides: a new direction in gastrointestinal endocrinology; Ishikawa MD M et al.; Investigation into gastrointestinal irritation from the use of erythromycin lead to the discovery of the gastrointestinal motor effect of this antibiotic . Erythromycin and gastrointestinal peptide motilin share many similar gastrokinetic activities, and studies indicate that erythromycin mimics the effect of motilin through motilin receptor agonism . Since erythromycin is readily available for clinical use, it may offer an alternative therapeutic approach to gastroparesis and related conditions . Several analogs of erythromycin without antimicrobial activity are also shown to possess similar motor effects, thus termed "motilides" . A growing number of motilides may expand our knowledge on gastrointestinal peptides. J Pept Res, 2004 Aug, 64(2), 65 - 71 A cumulative experience examining the effect of natural and synthetic antimicrobial peptides vs . Chlamydia trachomatis; Yasin B et al.; We tested the activity of 48 structurally diverse antimicrobial peptides against Chlamydia trachomatis, serovar L2 . The peptides' activity against C . trachomatis, serovar L2 was measured in 48-h McCoy cell shell vial assays . Peptides of 16-20 amino acids were more active than larger peptides, such as defensins . Beta-sheet protegrins, as well as alpha-helical peptides such as novispirin (G-10) were equally active . Enantiomers were as active as native structures . Moderate-sized circular mini-defensins were less effective against C . trachomatis . Moderate-sized cationic peptides may be useful in microbicide preparations designed to prevent chlamydial infection. J Oral Pathol Med, 2004 Aug, 33(7), 410 - 6 Salivary secretory leukocyte protease inhibitor increases in HIV infection; Lin AL et al.; BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is an antimicrobial protein found in saliva and having anti-HIV activity . The concentrations of SLPI in parotid and submandibular/sublingual (SMSL) saliva were determined in an HIV(+) population and compared with uninfected controls . The effect of highly active antiretroviral therapy (HAART) on the concentrations in saliva was determined . METHODS: Stimulated parotid and SMSL saliva was collected from 65 HIV(+) patients and 19 healthy controls . Flow rates, total protein and SLPI concentrations were determined as well as the effect of HAART on these measurements . RESULTS: Mean flow rates were reduced for parotid (64%) and SMSL (44%) saliva of HIV(+) patients . Flow rate reductions were unaffected by HAART . Total protein concentration in HIV(+) parotid saliva was increased 56%; patients on HAART had higher concentrations than control . For both groups, SLPI concentrations of SMSL saliva were twice that of parotid saliva . For HIV(+) patients SLPI concentrations of both saliva types were 70% greater than control; the increase in parotid saliva was greater for those taking HAART . For each saliva type, the secretory rate and specific SLPI protein concentration were not different between the groups . Patients with low CD4(+) counts had greater SLPI concentrations in parotid saliva than control . There was a negative correlation between CD4(+) counts and the SLPI concentration of parotid saliva . CONCLUSIONS: Salivary flow rate is decreased and the concentration of SLPI is increased in the presence of HIV infection . SLPI concentration in parotid and SMSL saliva is greater with HAART. Mem Inst Oswaldo Cruz, 2004 Mar, 99(2), 189 - 93 Epub 2004 Jun 24. Immunoblotting for the serodiagnosis of Helicobacter pylori infection in Brazilian patients with and without gastric carcinoma; Rocha AM et al.; We evaluated the performance of a commercial immunoblotting in the serodiagnosis of Helicobacter pylori infection in Brazilian patients . The presence of anti-H . pylori antibodies was also investigated in a group of 20 duodenal ulcer patients after successful treatment . One hundred and ninety one patients were studied . Among the 164 infected patients, 46 had gastric carcinoma . The duodenal ulcer patients were treated with antimicrobial drugs and the eradication of the microorganism was confirmed in all of them one month after the end of the treatment by the 13C-urea breath test . Sera were assayed for H . pylori antibodies using the Helicoblot 2.0 (Genelabs Diagnostics, Singapore) . The sensitivity, specificity, positive, and negative predictive values of the test were 93.9%, 92.6%, 98.7%, and 71.4%, respectively . The sensitivity of the test was similar in patients with (93.5%) and without (95.7%) gastric carcinoma . Twenty-four months after the end of the treatment, the band of 116 kDa was still detected in one of the patients . In conclusion, the Helicoblot 2.0 is an accurate test to diagnose H . pylori infection and although it can not be employed to monitor the bacterium eradication, it may be useful for diagnosing past infection, especially in gastric carcinoma patients. Clin Infect Dis, 2004 Jul 15, 39 Suppl 1, S44 - 8 The Infectious Diseases Society of America 2002 guidelines for the use of antimicrobial agents in patients with cancer and neutropenia: salient features and comments; Rolston KV; Infection remains the most common complication of chemotherapy-induced neutropenia . Bacterial infections predominate initially . Invasive fungal infections occur in patients with prolonged neutropenia . Chemoprophylaxis is recommended only for patients at high risk . Initial empirical therapy is based on local epidemiology and drug-susceptibility patterns . Patients at low risk can be treated as outpatients . Other patients need hospital-based, parenteral therapy . Several options are available, including combination regimens or monotherapy . Initial antimicrobial coverage against Pseudomonas species is necessary . Subsequent management depends on the nature of the febrile episode . If defervescence occurs within 3-5 days and no pathogen has been identified, the initial regimen or a suitable oral regimen can be used to complete a 7- to 10-day course . If the etiology has been established, therapy can be adjusted for optimal coverage (activity against gram-negative organisms must be maintained) . If fever persists for longer than 3-5 days, assessment for a fungal infection, a resistant organism, or a new infectious focus should be conducted and empirical antifungal therapy instituted. Clin Infect Dis, 2004 Jul 15, 39 Suppl 1, S32 - 7 Management of fever in neutropenic patients with different risks of complications; Klastersky J; Risk stratification of febrile neutropenic patients can have important implications in terms of management . The first prospectively validated risk scoring system was developed in 1992 . A subsequent scoring system was developed in 2000, in which a score of < or =21 predicts a <5% risk for severe complications . Oral combination therapy in an ambulatory or home care setting is acceptable for low-risk patients . Hospital admission is mandatory for high-risk patients . Intravenous monotherapy can be given if neutropenia is anticipated to be of short duration; it is also acceptable if neutropenia is expected to be more prolonged but the patients is stable and do not have an infectious focus . All other patients should receive combination therapy with an aminoglycoside, if infection with a gram-negative pathogen is suspected, or a glycopeptide, if a gram-positive organism is suspected . However, antimicrobial therapy with coverage against gram-negative organisms should always be provided because of the significant mortality associated with these infections. Chest, 2004 Jul, 126(1), 100 - 7 Limited impact of a multicenter intervention to improve the quality and efficiency of pneumonia care; Halm EA et al.; STUDY OBJECTIVES: To evaluate the impact of a multifactorial intervention to improve the quality, efficiency, and patient understanding of care for community-acquired pneumonia . DESIGN: Times series cohort study . SETTING: Four academic health centers in the New York City metropolitan area . PATIENTS OR PARTICIPANTS: All consecutive adults hospitalized for pneumonia during a 5-month period before (n = 1,013) and after (n = 1,081) implementation of an inpatient quality improvement (QI) initiative . INTERVENTIONS: A multidisciplinary team of opinion leaders developed evidence-based treatment guidelines and critical pathways, conducted educational sessions with physicians, distributed pocket reminder cards, promoted standardized orders, and developed bilingual patient education materials . MEASUREMENTS AND RESULTS: The average age was 71.4 years, and 44.1% of cases were low risk, 36.8% were moderate risk, and 19.2% were high risk . The preintervention and postintervention groups were well matched on age, sex, race, nursing home residence, pneumonia severity, initial presentation, and most major comorbidities . The intervention increased the use of guideline-recommended antimicrobial therapy from 78.1 to 83.4% (p = 0.003) . There was also a borderline decrease in the proportion of patients being discharged prior to becoming clinically stable, from 27.0 to 23.5% (p = 0.06) . However, there were no improvements in the other targeted indicators, including time to first dose of antibiotics, proportion receiving antibiotics within 8 h, timely switch to oral antibiotics, timely discharge, length of stay, or patient education outcomes . CONCLUSIONS: This real-world QI program was able to improve modestly on some quality indicators, but not effect resource use or patient knowledge of their disease . Changing physician and organizational behavior in academic health centers will require the development and implementation of more intensive, system-oriented strategies. Arch Intern Med, 2004 Jul 12, 164(13), 1451 - 6 A survey of knowledge, attitudes, and beliefs of house staff physicians from various specialties concerning antimicrobial use and resistance; Srinivasan A et al.; BACKGROUND: Examination of knowledge, attitudes, and beliefs of house staff physicians will be important in developing interventions to improve antimicrobial use and prevent resistance . METHODS: A 75-item survey was distributed to house staff physicians on nonpediatric services in a university teaching hospital . Knowledge was assessed with a 10-question quiz . RESULTS: The survey was completed by 179 (67%) of 269 house staff physicians on 5 specialties . Outside and inside the intensive care unit, 21% and 25% of respondents, respectively, reported that they were using antibiotics optimally . Surgeons were significantly more likely than other physicians to report that they were regularly seeking input into antimicrobial selections (P<.001) . Of the 170 physicians who completed the survey, 88% agreed antibiotics are overused in general and 72% also agreed this was the case at their institution (r = 0.56; P<.05); 96% agreed that hospitals in general face serious problems with antibiotic resistance and 93% agreed that their hospital faces these same problems (r = 0.57; P<.05); 97% agreed that better use of antibiotics would reduce resistance; 32% stated that they had not had formal teaching on antimicrobial agents in the last year (medicine residents reported significantly more formal teaching than others {P =.001}); and 90% wanted more education about antimicrobials and 67% wanted more feedback on antimicrobial selections . The mean antimicrobial quiz score was 28%, with medicine residents scoring significantly higher than others (P =.04) . Upper-level residents did not perform better than interns . CONCLUSIONS: This survey (1) revealed that house staff are aware of the importance of antimicrobial resistance and believe better antimicrobial use will help this problem and (2) demonstrated differences between specialties with respect to antimicrobial use and knowledge . House staff at our hospital have suboptimal knowledge about antimicrobials, and this knowledge did not increase appreciably over the course of their training . Antimicrobial education is needed and is likely to be well received by house staff physicians in academic centers but may be more effective if it is tailored to specific specialties. Arch Gerontol Geriatr, 2004 Sep-Oct, 39(2), 111 - 6 Pneumonia in elderly patients with preexisting respiratory disease; Sumi M et al.; To evaluate the optimal duration of appropriate antibiotic therapy for pneumonia in elderly patients with preexisting respiratory disease, we studied improvement of infectious parameters in these patients . The medical record database was used to identify patients admitted with the following characteristics: primary diagnosis of benign respiratory disease; aged 65 years or over; no active malignant diseases in any organs; and at least one admission for pneumonia during April 2001 to May 2003 . We observed 47 pneumonia episodes in 30 patients . Elevated CRP levels more than 8.0 mg/ml and leukocytosis more than 10.0 x 10(3) mm(-3) was seen in 21 and 29 pneumonia episodes, respectively . With appropriate intravenous antimicrobial therapy, average of CRP levels on day 0 (9.16 +/- 6.81 mg/dl) decreased to 5.18 +/- 4.67 mg/dl on day 3 (P = 0.0073) . In more than 70% of pneumonia episodes, serum levels of CRP normalized on day 10 . Average of leukocyte counts on day 0 ((12.3 +/- 4.7) x 10(3) mm(-3)) decreased to (8.1 +/- 3.5) x 10(3) mm(-3) on day 3 (P = 0.0001) . In more than 80% of pneumonia episodes, leukocyte count normalized on day 7 . The clinical response to appropriate antimicrobial therapy for pneumonia occurs within the first 3 days of therapy . Duration of intravenous antimicrobial therapy for pneumonia in these patients of 10 days would be sufficient and could prevent recurrent infection with resistant bacteria. Spectrochim Acta A Mol Biomol Spectrosc, 2004 Aug, 60(10), 2201 - 8 X-band electron paramagnetic resonance, optical spectra and some biological (SOD and antimicrobial activity) studies of the copper(II) complexes: a plausible model for superoxide dismutase; Patel RN; The synthesis and characterization of homobinuclear complex by 2-ethylimidazole is reported along with two mononuclear complexes . Magnetic measurements and electron parameter resonance (e.p.r.) spectroscopy of the homobinuclear complex have shown an antiferromagnetic exchange interaction . Superoxide dismutase and antimicrobial activities of these complexes have also been measured. Biochemistry, 2004 Jul 20, 43(28), 9140 - 50 Cyclization increases the antimicrobial activity and selectivity of arginine- and tryptophan-containing hexapeptides; Dathe M et al.; Arginine- and tryptophan-rich motifs have been identified in antimicrobial peptides with various secondary structures . We synthesized a set of linear hexapeptides derived from the sequence AcRRWWRF-NH(2) by substitution of tryptophan (W) by tyrosine (Y) or naphthylalanine (Nal) and by replacement of arginine (R) by lysine (K) to investigate the role of cationic charge and aromatic residues in membrane activity and selectivity . A second set of corresponding head-to-tail cyclic analogues was prepared to analyze the role of conformational constraints . The biological activity of the linear peptides followed the order Nal- >> W- > Y-containing compounds and slightly decreased upon R-K substitution . A pronounced activity-improving and bacterial selectivity-enhancing effect was found upon cyclization of the R- and W-bearing parent peptide, whereas the activity-modifying effect of cyclization of Y- and Nal-containing peptides was low . The analysis of the driving forces of peptide interaction with model membranes showed that the activities correlated with the partition coefficients and the depths of peptide insertion into neutral and negatively charged lipid bilayers . Spectroscopic studies, RP-HPLC, and titration calorimetry implied that the combination of cationic and aromatic amino acid composition and conformational rigidity afforded a membrane-active, amphipathic structure with a highly charged face opposed by a cluster of aromatic side chains . However, threshold values of low and high hydrophobicity seemed to exist beyond which the activity-enhancing effect of cyclization was negligible . The results suggest that cyclization of small peptides of an appropriate amino acid composition may serve as a promising strategy in the design of antimicrobial peptides. Nat Prod Res, 2004 Oct, 18(5), 427 - 31 2,4,5-Tribromo-1H-imidazole in the egg masses of three muricid molluscs; Benkendorff K et al.; From analysis by gas chromatography/mass spectrometry (GC/MS), the presence of either 2,4,5-tribromo-1H-imidazole (1) or 3,4,5-tribromo-1H-pyrazole (2) was tentatively identified in lipophilic extracts from the egg masses of three muricid molluscs . Synthesis of these compounds, followed by comparison of the GC retention times and fragmentation patterns from electron impact MS, with those of the natural products, indicated that it was 2,4,5-tribromo-1H-imidazole rather than the pyrazole . This imidazole is likely to be responsible for some of the antimicrobial activity observed in the egg extracts . This is the first report of this compound from a natural source. Pediatr Infect Dis J, 2004 Jul, 23(7), 681 - 3 Vagal nerve stimulator pocket infections; Patel NC et al.; Vagal nerve stimulator pocket infections are uncommon but can cause considerable morbidity . We describe 3 children from our institution and 8 others previously reported with infection after vagal nerve stimulator implantation for seizure control . Infection was suppressed but recurred despite appropriate antimicrobial therapy when the device remained in situ . Device removal was required in all patients to achieve cure. Science, 2004 Jul 9, 305(5681), 205 - 8 Therapeutic vaccines for chronic infections; Autran B et al.; Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy . We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases- human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated. FASEB J, 2004 Sep, 18(12), 1447 - 9 Epub 2004 Jul 09. A new type of antimicrobial protein with multiple histidines from the hard tick, Amblyomma hebraeum; Lai R et al.; A novel 11 kDa antimicrobial protein, named as hebraein, and having a unique amino acid sequence, was purified from the hemolymph of fed female Amblyomma hebraeum ticks . A full-length cDNA clone encoding hebraein was isolated from a cDNA library made from tick synganglia . Hebraein consists of 102 amino acids, including 6 cysteine residues; has 9 histidines in its C-terminal domain that are mainly present as HX repeats; and has no significant similarity to any known protein . The secondary structure prediction is very clearly all alpha-helical (4-6 helices) except for a very short extension at the C terminus . Such high alpha-helical content is quite different from known antimicrobial proteins . Recombinant hebraein and a mutant lacking the histidine residues in the C-terminal domain were constructed and expressed . Assayed at the slightly acidic pH equivalent of fed female tick hemolymph, the wild-type and the histidine-rich recombinant hebraein had stronger antimicrobial activities than the histidine-deficient mutant . The pH-dependent properties of histidine-rich antimicrobial proteins may allow the design of agents that would function selectively in specific pH environments . The results from protein profiling of hemolymph, analyzed by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry combined with ProteinChip technology and RT-PCR analysis suggested that this antimicrobial protein was up-regulated by blood feeding . Our findings describe a new type of antimicrobial protein with multiple cysteine and histidine residues, and with unique secondary structure. Am J Physiol Gastrointest Liver Physiol, 2004 Nov, 287(5), G1062 - 9 Epub 2004 Jul 08. Regulated production of the chemokine CCL28 in human colon epithelium; Ogawa H et al.; The chemokine CCL28 is constitutively expressed by epithelial cells at several mucosal sites and is thought to function as a homeostatic chemoattractant of subpopulations of T cells and IgA B cells and to mediate antimicrobial activity . We report herein on the regulation of CCL28 in human colon epithelium by the proinflammatory cytokine IL-1, bacterial flagellin, and n-butyrate, a product of microbial metabolism . In vivo, CCL28 was markedly increased in the epithelium of pathologically inflamed compared with normal human colon . Human colon and small intestinal xenografts were used to model human intestinal epithelium in vivo . Xenografts constitutively expressed little, if any, CCL28 mRNA or protein . After stimulation with the proinflammatory cytokine IL-1, CCL28 mRNA and protein were significantly increased in the epithelium of colon but not small intestinal xenografts, although both upregulated the expression of another prototypic chemokine, CXCL8, in response to the identical stimulus . In studies of CCL28 regulation using human colon epithelial cell lines, proinflammatory stimuli, including IL-1, bacterial flagellin, and bacterial infection, significantly upregulated CCL28 mRNA expression and protein production . In addition, CCL28 mRNA expression and protein secretion by those cells were significantly increased by the short-chain fatty acid n-butyrate, and IL-1- or flagellin-stimulated upregulation of CCL28 by colon epithelial cells was synergistically increased by pretreatment of cells with n-butyrate . Consistent with its upregulated expression by proinflammatory stimuli, CCL28 mRNA expression was attenuated by pharmacological inhibitors of NF-kappaB activation . These findings indicate that CCL28 functions as an "inflammatory" chemokine in human colon epithelium and suggest the notion that CCL28 may act to counterregulate colonic inflammation. Arch Biochem Biophys, 2004 Aug 15, 428(2), 170 - 8 Molecular cloning and biological characterization of novel antimicrobial peptides, pilosulin 3 and pilosulin 4, from a species of the Australian ant genus Myrmecia; Inagaki H et al.; Venom of an Australian ant species of the Myrmecia pilosula species complex (mss . name Myrmecia banksi Taylor) contains two major allergenic peptides, pilosulin 1 and pilosulin 2 . To obtain novel cDNA clones that encode the pilosulin-related bioactive peptides, mRNA of another Myrmecia species was subjected to RT-PCR in which the forward primer corresponds to a nucleotide sequence in the leader sequences of pilosulin 1 and pilosulin 2 . As a result, we isolated cDNA clones encoding the novel antimicrobial peptides pilosulin 3 and pilosulin 4 . The nucleotide and the amino acid sequences of all four pilosulins have high homology except for the mature peptide coding regions . Synthetic pilosulin 3 and pilosulin 4 peptides displayed antimicrobial activity with histamine-releasing and low hemolytic activities. Int J Food Microbiol, 2004 Aug 1, 94(3), 255 - 61 Bactericidal activity of wasabi (Wasabia japonica) against Helicobacter pylori; Shin IS et al.; In this study, the bactericidal activity of Korean and Japanese wasabi roots, stems and leaves against Helicobacter pylori were examined . Allyl isothiocyanate (AIT) in roots, stems and leaves of Korean wasabi were 0.75, 0.18 and 0.32 mg/g, respectively . AIT in roots, stems and leaves of Japanese wasabi were 1.18, 0.41 and 0.38 mg/g, respectively . All parts of wasabi showed bactericidal activities against H . pylori strain NCTC 11637, YS 27 and YS 50 . The leaves of both wasabi showed the highest bactericidal activities with the minimum bactericidal concentration of 1.05-1.31 mg of dry weight/ml against three strains of H . pylori . The roots showed a little lower bactericidal activity with 2.09-4.17 mg of dry weight/ml against them . The main component related to antimicrobial activity in wasabi is well known to be AIT . In this study, the bactericidal activity of leaves was higher than that of roots, although AIT amount of leaves was lower than that of roots . These results suggest that certain components besides AIT in wasabi are effective in killing H . pylori. Autoimmun Rev, 2004 Jun, 3(4), 243 - 9 Adverse events of desirable gain in immunocompetence: the Immune Restoration Inflammatory Syndromes; Stoll M et al.; Augmentation of inflammation may occur during immune reconstitution in a immunocompromised host . This phenomenon is able to cause atypical inflammatory disorders, synonymously summarized as 'Immune Reconstitution Syndrome', 'Immune Restoration Disease' and 'Immune Restoration Inflammatory Syndrome' (IRIS) . Immune reconstitution occurs, if temporarily use of immunosuppressive agents was terminated or if highly active antiretroviral therapy in human immunodeficiency virus positive individuals with secondary immunodeficiency was initiated . Unexpected deterioration of inflammatory disease and atypical clinical features, resembling symptoms of autoimmune disease may arise . They have to be distinguished from intercurrent infection and rheumatic disease, respectively . Treatment of IRIS would consist of both potential differential diagnoses: use of anti-inflammatory and immunosuppressive drugs like in autoimmune disorders as well as antimicrobial chemotherapy to decrease the burden of pathogen like in infectious disease . Therefore, awareness for IRIS is of increasing importance from a clinical point of view . However, diagnostic criteria and standards of treatment still have to be defined. Anal Biochem, 2004 Aug 1, 331(1), 33 - 9 Effects of detergent alkyl chain length and chemical structure on the properties of a micelle-bound bacterial membrane targeting peptide; Keifer PA et al.; The effects of phospholipid or detergent chain length on the structure and translational diffusion coefficient of the membrane-targeting peptide corresponding to the N-terminal amphipathic sequence of Escherichia coli enzyme IIA(Glc) were investigated by nuclear magnetic resonance (NMR) spectroscopy . Three anionic phospholipids (dihexanoyl phosphatidylglycerol, dioctanoyl phosphatidylglycerol, and didecanoyl phosphatidylglycerol) and four lipid-mimicking anionic detergents (sodium hexanesulfonate, 2,2-dimethyl-silapentane-5-sulfonate, sodium nonanesulfonate, and sodium dodecylsulfate) were evaluated . In all cases, the cationic peptide adopts an amphipathic helical structure . While the chain length of the two-chain phospholipids has a negligible effect on the peptide conformation, the effect of chain length of those single-chain detergents on the helix length is more pronounced . The diffusion coefficients of the peptide/micelle complexes were found to correlate with the chain lengths of both the lipid and the detergent groups . Taken together, short-chain anionic phospholipids are proposed to be useful membrane-mimetic models for the structural elucidation of membrane-binding peptides such as cationic antimicrobial peptides . DSS does not form micelles by itself according to the diffusion coefficient data, but it does associate with this cationic peptide . Consequently, both DSS and its analog may be chosen as NMR chemical shift reference compounds depending on the nature of the biomolecules under investigation. Peptides, 2004 Jul, 25(7), 1075 - 7 In vitro activity of protegrin-1 and beta-defensin-1, alone and in combination with isoniazid, against Mycobacterium tuberculosis; Fattorini L et al.; The antimicrobial peptide protegrin-1 (PG-1) inhibited the growth in vitro of drug-susceptible and multidrug-resistant Mycobacterium tuberculosis; a lower activity was shown by human beta-defensin-1 (HBD-1) against both strains . The combination of PG-1 or HBD-1 with isoniazid significantly reduced M . tuberculosis growth in comparison with the peptides or isoniazid alone. Curr Opin Immunol, 2004 Aug, 16(4), 499 - 505 New models for the study of Mycobacterium-host interactions; Pozos TC et al.; The outcome of Mycobacterium infection is determined by a series of complex interactions between the bacteria and host immunity . Traditionally, mammalian models and cultured cells have been used to study these interactions . Recently, ameba (Dictyostelium), fruit flies (Drosophila) and zebrafish, amenable to forward genetic screens, have been developed as models for mycobacterial pathogenesis . Infection of these hosts with mycobacteria has allowed the dissection of intracellular trafficking pathways (Dictyostelium) and the roles of phagocytic versus antimicrobial peptide responses (Drosophila) . Real-time visualization of the optically transparent zebrafish embryo/larva has elucidated mechanisms by which Mycobacterium-infected leukocytes migrate and subsequently aggregate into granulomas, the hallmark pathological structures of tuberculosis. Mayo Clin Proc, 2004 Jul, 79(7), 927 - 30 Linezolid-associated peripheral neuropathy; Rho JP et al.; Linezolid is the first drug in a new class of synthetic antimicrobials, the oxazolidinones, to be approved by the Food and Drug Administration . Linezolid is active against methicillin- and vancomycin-resistant gram-positive microorganisms . We describe 2 patients who developed peripheral neuropathy after prolonged treatment with linezolid . Linezolid-associated peripheral neuropathy has not been well documented . Most reported cases of linezolid-associated peripheral neuropathy have occurred in patients who took linezolid for a period longer than the recommended 28 or fewer days . Health care providers must be alert to the potential for serious adverse effects associated with linezolid use, including peripheral neuropathy. Support Care Cancer, 2004 Dec, 12(12), 826 - 32 Epub 2004 Jul 08. Fever in neutropenia in children and adolescents: evolution over time of main characteristics in a single center, 1993-2001; Ammann RA et al.; GOALS OF WORK: To assess the evolution over time of main characteristics of episodes of fever in severe chemotherapy-induced neutropenia (FN) in children and adolescents with cancer treated for FN following nonmyeloablative chemotherapy, to compare the results with the experiences of other centers, and to assess the impact of the changes found on management of FN and on risk prediction rules . PATIENTS AND METHODS: Retrospective cohort study of all children and adolescents up to 18 years presenting with FN in a single pediatric oncology unit between 1993 and 2001 . MAIN RESULTS: In 132 patients, 364 episodes of FN were reported . The relative incidence of FN increased significantly over time in patients with precursor B-cell acute lymphoblastic leukemia (PBC-ALL), reflecting the increased intensity of chemotherapy . At presentation with FN, the proportions of patients (1) with PBC-ALL versus other malignancies, (2) with other malignancies being in complete remission, (3) with a central venous catheter, and (4) with shaking chills all significantly increased over time (overall proportions, 64%, 60%, 50%, and 5%, respectively; p <0.001 for all) . In 337 (93%) episodes, ceftriaxone plus amikacin was used as empirical broad spectrum antimicrobial therapy . CONCLUSIONS: This study demonstrates that some characteristics of FN, though not necessarily its management, change over time, implying regular update of risk prediction rules . In contrast to other centers, the first-line antimicrobial therapy did not need modification because of changing resistance patterns. Rev Saude Publica, 2004 Jun, 38(3), 358 - 64 Epub 2004 Jul 08. {Use of drugs to treat respiratory tract infections in the community}; Berquo LS et al.; OBJECTIVE: This study describes the utilization of drugs to treat respiratory tract infections in a community setting . The description of antimicrobial and non-antimicrobial drugs use is important to design interventions aimed at improving treatment strategies for these common illnesses . METHODS: In a population-based cross-sectional study, 6145 individuals living in an urban area in southern Brazil were inquired about the use of drugs for the treatment of respiratory tract infections in the 30 days previous to the interview . The Pearson chi-square test was used for statistical analyses . RESULTS: The global prevalence of respiratory infections treated with drugs was 6.3% . The prevalence was higher for children under 4 years of age (18%) and lower for the elderly (3%; p<0.001) . Fifty-nine percent of the individuals used antimicrobials to treat respiratory infections . "Sore throat" was the main clinical condition associated with drug use (41%) . Amoxicilin was the antimicrobial drug most frequently used (38%), while non-steroidal anti-inflamatory drugs were the most frequent among the non-antimicrobial drugs (27%) . CONCLUSIONS: Antimicrobials were used in nearly 60% of the respiratory tract infections treated with some drug, even though they are mostly viral in their origin . The indiscriminate use of these drugs not only raises the costs of treatments, but may also lead to the emergence of bacterial resistance against the antimicrobials. J Clin Microbiol, 2004 Jul, 42(7), 3137 - 41 Cross-resistance between fluconazole and ravuconazole and the use of fluconazole as a surrogate marker to predict susceptibility and resistance to ravuconazole among 12,796 clinical isolates of Candida spp; Pfaller MA et al.; Cross-resistance within a class of antimicrobial agents is a problem that is often encountered with antibacterial agents, and it is also an issue with antifungal agents . A current example is ravuconazole, a new triazole antifungal with an expanded spectrum and potency against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens . The present study addresses the issue of cross-resistance between fluconazole and ravuconazole and the use of fluconazole as a surrogate marker to predict the susceptibility of Candida spp . to ravuconazole . Reference broth microdilution MIC results for 12,796 strains of Candida spp . isolated from more than 200 medical centers worldwide were used . Ravuconazole MICs and tentative interpretive categories (susceptible, </=1 microg/ml; resistant, >/=2 microg/ml) were compared with those of fluconazole by using regression statistics and error rate bounding analyses . For all 12,796 isolates, the absolute categorical agreement rate was 92.5% (rate of false-susceptible results, or very major errors {VME}, 0.1%) . Ravuconazole was active (MIC, </=1 microg/ml) against 99.9% of the fluconazole-susceptible isolates, 96% of the fluconazole-susceptible dose-dependent isolates, and 49% of the fluconazole-resistant isolates, including 99% of the Candida krusei isolates . Since ravuconazole is 16- to 32-fold more potent than fluconazole, the performance of fluconazole as a surrogate marker for ravuconazole susceptibility was improved by designating those isolates with fluconazole MICs of </=32 microg/ml susceptible to ravuconazole, resulting in a categorical agreement rate of 98.3%, with a VME rate of 0.3% (99 and 0.4%, respectively, when C . krusei was omitted) . Cross-resistance between fluconazole and ravuconazole applies most directly to fluconazole-resistant Candida glabrata and is variable among other species of Candida . Fluconazole may serve as a surrogate marker to predict the susceptibility of Candida spp . to ravuconazole. Biochem Pharmacol, 2004 Aug 1, 68(3), 549 - 61 Membrane-related effects underlying the biological activity of the anthraquinones emodin and barbaloin; Alves DS et al.; Commercial plant extracts containing anthraquinones are being increasingly used for cosmetics, food and pharmaceuticals due to their wide therapeutic and pharmacological properties . In this work, the interaction with model membranes of two representative 1,8-dihydroxyanthraquinones, barbaloin (Aloe) and emodin (Rheum, Polygonum), has been studied in order to explain their effects in biological membranes . Emodin showed a higher affinity for phospholipid membranes than barbaloin did, and was more effective in weakening hydrophobic interactions between hydrocarbon chains in phospholipid bilayers . Whereas emodin induced the formation of hexagonal-H(II) phase, barbaloin stabilized lamellar structures . Barbaloin promoted the formation of gel-fluid intermediate structures in phosphatidylglycerol membranes at physiological pH and ionic strength values . It is proposed that emodin's chromophore group is located at the upper half of the membrane, whereas barbaloin's one is in a deeper position but having its glucopyranosyl moiety near the phospholipid/water interface . Moreover, membrane disruption by emodin or barbaloin showed specificity for the two major phospholipids present in bacterial membranes, phosphatidylethanolamine and phosphatidylglycerol . In order to relate their strong effects on membranes to their biological activity, the capacity of these compounds to inhibit the infectivity of the viral haemorrhagic septicaemia rhabdovirus (VHSV), a negative RNA enveloped virus, or the growth of Escherichia coli was tested . Anthraquinone-loaded liposomes showed a strong antimicrobial activity whereas these compounds in their free form did not . Both anthraquinones showed antiviral activity but only emodin was a virucidal agent . In conclusion, a molecular mechanism based on the effect of these compounds on the structure of biological membranes is proposed to account for their multiple biological activities . Anthraquinone-loaded liposomes may suppose an alternative for antimicrobial, pharmaceutical or cosmetic applications. Lett Appl Microbiol, 2004, 39(2), 169 - 73 Decontamination effect of electrolysed NaCl solutions on carp; Mahmoud BS et al.; AIMS: To evaluate the efficacy of electrolysed NaCl solutions (EW) for disinfecting bacterial isolates from carp, and the potential application of EW to reducing the bacterial load in whole carp and carp fillets . METHODS AND RESULTS: EW was produced by using a two-compartment batch-type electrolysed apparatus . Pure cultures (in vitro), whole carp (skin surface) and carp fillets were treated with EW to detect its antimicrobial effects . The anodic solution {EW (+)} completely inhibited growth of the isolates . Furthermore, dipping the fish samples in EW (+) reduced the mean total count of aerobic bacteria on the skin of whole carp and in fillets by 2.8 and 2.0 log(10), respectively . The cathodic solution {EW (-)} also reduced growth of the isolates from carp by ca 1.0 log(10) . Moreover, the total counts of aerobic bacteria in whole carp (on the skin) and fillets were reduced by 1.28 and 0.82 log(10), respectively . CONCLUSIONS: EW (+) has a strong bactericidal effect on bacteria isolated from carp . SIGNIFICANCE AND IMPACT OF THE STUDY: Treatment with EW (+) could extend the shelf life of these fish. Mol Plant Microbe Interact, 2004 Jul, 17(7), 780 - 8 Inorganic cations mediate plant PR5 protein antifungal activity through fungal Mnn1- and Mnn4-regulated cell surface glycans; Salzman RA et al.; Antimicrobial activities of many defense proteins are profoundly altered by inorganic cations, thereby controlling disease pathologies in a number of mammalian systems, such as cystic fibrosis in humans . Protein-based active defense systems in plants also are influenced by cations; however, little is known of how these cation effects are mediated . Cytotoxicity of the pathogenesis-related protein osmotin against the model fungus Saccharomyces cerevisiae was progressively abolished by K+ . By the use of S . cerevisiae mannosylation mutants, this effect was shown to require mannosephosphate residues in the cell wall . However, osmotin activity was not suppressed by even high concentrations of Ca2+ . Rather, submillimolar levels of Ca2+ specifically facilitated osmotin's activity, as well as its binding to the cell surface . This effect also was dependent on mannosephosphate groups on the cell surface, and appeared to require negative charge on a portion of the osmotin protein . Results suggest that Ca2+ modulates osmotin action by facilitating its binding to the fungal cell surface, but that K+ blocks this interaction by competing for binding to mannosephosphate groups . Therefore, we have identified glycan interaction as a mechanism for antimicrobial protein activity modulation by cations, a pattern that may apply to diverse innate defense responses. Orthopade, 2004 Aug, 33(8), 885 - 92 {Nanoparticulate silver . A new antimicrobial substance for bone cement}; Alt V et al.; BACKGROUND: Multiresistant bacteria have become an important problem in prosthetic joint infections . Their frequent resistance against gentamicin, which is commonly used in antibiotic-loaded bone cements, makes a new prophylaxis necessary . METHODS: PMMA-cement was loaded with 1% nanoparticulate silver and its antibacterial activity tested in vitro against gentamicin-resistant MRSE and MRSA strains as well as being compared to the activity of plain and gentamicin-loaded bone cements . A quantitative elution testing was also done to study the potentially cytotoxic effects of NanoSilver cement . RESULTS: Unloaded and PMMA-cement loaded with 2% gentamicin did not exhibit any antibacterial activity against MRSE and MRSA . At 1%, NanoSilver cement completely inhibited the proliferation of MRSA and MRSE . NanoSilver bone cement did not show any significant differences compared to the non-toxic control group . CONCLUSIONS: If these promising in vitro results can be confirmed in vivo, NanoSilver bone cement may be of considerable value in total joint arthroplasty. Cell Mol Life Sci, 2004 Jul, 61(14), 1751 - 63 The scorpine family of defensins: gene structure, alternative polyadenylation and fold recognition; Zhu S et al.; Small cationic antimicrobial peptides (SCAMPs) as effectors of animal innate immunity provide the first defense against infectious pathogens . This class of molecules exists widely in invertebrate hemolymph and vertebrate skin secretion, but animal venoms are emerging as a new rich resource . Scorpine is a unique scorpion venom defensin peptide that has an extended amino-terminal sequence similar to cecropins . From the African scorpion Opistophthalmus carinatus venom gland, we isolated and identified several cDNAs encoding four new homologs of scorpine (named opiscorpines 1-4) . Importantly, we show for the first time the existence of multiple opiscorpine mRNAs with variable 3' untranslated regions (UTRs) in the venom gland, which may be generated by alternative usage of polyadenylation signals . The complete opiscorpine gene structure including its promoter region is determined by genomic DNA amplification . Two large introns were found to be located within the 5' UTR and at the boundary of the mature peptide-coding region . Such a gene structure is distinct, when compared with other scorpion venom peptide genes . However, a comparative promoter analysis revealed that both opiscorpine and scorpion venom neurotoxins share a similar promoter organization . Sequence analysis and structural modeling allow us to group the scorpines and scorpion long-chain K-channel toxins together into one family that shares a similar fold with two distinct domains . The N-terminal cecropin-like domain displaying a clear antimicrobial activity implies that the scorpine family represents a group of real naturally occurring hybrids . Based on the phylogenetic analysis, a possible cooperative interaction between the N and C domains is elucidated, which provides an evolutionary basis for the design of a new class of anti-infectious drugs. Curr Opin Infect Dis, 2004 Aug, 17(4), 357 - 61 Prevention and treatment of cytomegalovirus infection in solid organ transplant recipients; Pereyra F et al.; PURPOSE OF REVIEW: Cytomegalovirus remains the single most important pathogen affecting solid organ transplant recipients . Its importance lies both in its effects and as a model for deciphering the clinical impact and management of other agents such as hepatitis C virus and other herpes viruses such as human herpes virus-6 and 7 . The effects of cytomegalovirus infection in these patients can be divided into two categories: the direct causation of a wide variety of infectious disease syndromes; and the indirect effects, which include contributing to the net state of immunosuppression, allograft injury, and potentiating posttransplant lymphoproliferative disease . RECENT FINDINGS: The advent of valganciclovir, with its excellent oral bioavailability, combined with intravenous ganciclovir have provided powerful tools for controlling the direct effects of cytomegalovirus, particularly with the recognition that the intensity of the antiviral therapy has to be linked to the intensity of the immunosuppression required.Unfortunately, far less is known about the efficacy of antiviral therapy in managing the indirect effects of cytomegalovirus . Preliminary data suggest antiviral prophylaxis protects against acute allograft injury, as well as decreasing the incidence of some opportunistic infection . SUMMARY: A great deal of progress has been made in the prevention and treatment of the infectious disease syndromes caused by cytomegalovirus, with the development of the concept of the therapeutic prescription . This has two components: an immunosuppressive component to prevent and treat rejection and an antimicrobial component to make it safe . Much more information, however, is required. J Leukoc Biol, 2004 Sep, 76(3), 648 - 56 Epub 2004 Jul 07. Urokinase-deficient and urokinase receptor-deficient mice have impaired neutrophil antimicrobial activation in vitro; Gyetko MR et al.; Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87) . We have shown that neutrophil recruitment to the lung during P . aeruginosa pneumonia is impaired in uPAR-deficient (uPAR-/-) mice but is normal in uPA-/- mice . However, both uPA-/- mice and uPAR-/- mice have impaired lung clearance of P . aeruginosa compared with wild-type (WT) mice . To determine the role of uPA and uPAR in antibacterial host defense, we compared neutrophil bacterial-phagocytosis, respiratory burst, and degranulation among uPA-/-, uPAR-/-, and WT mice . Neutrophil phagocytosis was significantly diminished comparing uPA-/- and uPAR-/- mice with WT mice at all time points . The generation of superoxide by both uPA-/- and uPAR-/- neutrophils was about half of that seen in WT neutrophils . Degranulation of azurophilic granules was significantly diminished in uPA-/- neutrophils compared with either uPAR-/- or WT neutrophils . By contrast, agonist-stimulated release of specific granules was not diminished in either uPA-/- or uPAR-/- mice compared with WT . We conclude that the uPA/uPAR system modulates several of the crucial steps in neutrophil activation that result in bacterial killing and effective innate host defense. Biophys J, 2004 Jul, 87(1), 662 - 74 Secondary structure and lipid contact of a peptide antibiotic in phospholipid bilayers by REDOR; Toke O et al.; The chemical shifts of specific (13)C and (15)N labels distributed throughout KIAGKIA-KIAGKIA-KIAGKIA (K3), an amphiphilic 21-residue antimicrobial peptide, prove that the peptide is in an all alpha-helical conformation in the bilayers of multilamellar vesicles (MLVs) containing dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol (1:1) . Rotational-echo double-resonance (REDOR) (13)C{(31)P} and (15)N{(31)P} experiments on the same labeled MLVs show that on partitioning into the bilayer, the peptide chains remain in contact with lipid headgroups . The amphipathic lysine side chains of K3 in particular appear to play a key role in the electrostatic interactions with the acidic lipid headgroups . In addition to the extensive peptide-headgroup contact, (13)C{(19)F} REDOR experiments on MLVs containing specifically (19)F-labeled lipid tails suggest that a portion of the peptide is surrounded by a large number of lipid acyl chains . Complementary (31)P{(19)F} REDOR experiments on these MLVs show an enhanced headgroup-lipid tail contact resulting from the presence of K3 . Despite these distortions, static (31)P NMR lineshapes indicate that the lamellar structure of the membrane is preserved. Biophys J, 2004 Jul, 87(1), 396 - 407 Conformation of peptides in lipid membranes studied by x-ray grazing incidence scattering; Spaar A et al.; Although the antimicrobial, fungal peptide alamethicin has been extensively studied, the conformation of the peptide and the interaction with lipid bilayers as well as the mechanism of channel gating are still not completely clear . As opposed to studies of the crystalline state, the polypeptide structures in the environment of fluid bilayers are difficult to probe . We have investigated the conformation of alamethicin in highly aligned stacks of model lipid membranes by synchrotron-based x-ray scattering . The (wide-angle) scattering distribution has been measured by reciprocal space mappings . A pronounced scattering signal is observed in samples of high molar peptide/lipid ratio which is distinctly different from the scattering distribution of an ideal helix in the transmembrane state . Beyond simple models of ideal helices, the data is analyzed in terms of models based on atomic coordinates from the Brookhaven Protein Data Bank, as well as from published molecular dynamics simulations . The results can be explained by assuming a wide distribution of helix tilt angles with respect to the membrane normal and a partial insertion of the N-terminus into the membrane. Biol Reprod, 2004 Nov, 71(5), 1638 - 45 Epub 2004 Jul 07. Effect of candidate vaginally-applied microbicide compounds on recognition of antigen by CD4+ and CD8+ T lymphocytes; Milligan GN et al.; Vaginally applied antimicrobial compounds (microbicides) are being developed as an alternative method for preventing the spread of sexually transmitted diseases . In addition to identifying compounds effective against a spectrum of sexually transmitted pathogens, it will be important to ensure that these compounds are safe . Avoiding toxicity, inflammatory responses, or alteration of the function of resident immune cells are important considerations for the development of vaginally applied microbicides . Studies were performed with two classes of candidate microbicide compounds to determine if they would interfere with the recognition of antigen by CD4(+) and CD8(+) T lymphocytes . The presence of nontoxic concentrations of the anionic detergent cholic acid or the sulfated polymer lambda carrageenan did not inhibit recognition of immune peptide by antigen-specific T cells . However, antigen recognition by both CD4(+) and CD8(+) T lymphocytes was inhibited in the presence of the naphthalene sulfonate polymer PRO 2000 . Brief (4-h) exposure of antigen-presenting cells or T cells to PRO 2000 did not result in inhibition of antigen uptake and processing by antigen-presenting cells or the ability of specific T cells to respond to antigen stimulation, suggesting that the inhibition was temporary . Binding of antibodies specific for CD18, CD8, and CD3 was impaired in the presence of PRO 2000, suggesting that the mechanism by which this microbicide inhibits T cell recognition of antigenic peptide may involve masking or internalization of surface proteins involved in T cell signaling or stabilizing T cell-antigen-presenting cell interactions . The assays described in this study represent a useful means to screen candidate topical microbicide compounds for inappropriate interactions with immune cells and may be useful for prioritization of candidate microbicide compounds. Biochem Biophys Res Commun, 2004 Jul 30, 320(3), 979 - 91 Molecular models for shikimate pathway enzymes of Xylella fastidiosa; Arcuri HA et al.; The Xylella fastidiosa is a bacterium that is the cause of citrus variegated chlorosis (CVC) . The shikimate pathway is of pivotal importance for production of a plethora of aromatic compounds in plants, bacteria, and fungi . Putative structural differences in the enzymes from the shikimate pathway, between the proteins of bacterial origin and those of plants, could be used for the development of a drug for the control of CVC . However, inhibitors for shikimate pathway enzymes should have high specificity for X . fastidiosa enzymes, since they are also present in plants . In order to pave the way for structural and functional efforts towards antimicrobial agent development, here we describe the molecular modeling of seven enzymes of the shikimate pathway of X . fastidiosa . The structural models of shikimate pathway enzymes, complexed with inhibitors, strongly indicate that the previously identified inhibitors may also inhibit the X . fastidiosa enzymes. J Appl Microbiol, 2004, 97(2), 371 - 7 Effects of antimicrobial treatment on fiberglass-acrylic filters; Cecchini C et al.; AIMS: The aims of the present study were to: (i) analyse a group of antimicrobial agents and to select the most active against test microbial strains; (ii) test the effect of the antimicrobial treatment on air filters in order to reduce microbial colonization . METHODS AND RESULTS: Different kinds of antimicrobial agents were analysed to assess their compatibility with the production process of air filter media . The minimal inhibitory concentration for each antimicrobial agent was determined against a defined list of microbial strains, and an antimicrobial activity assay of filter prototypes was developed to determine the most active agent among the compatible antimicrobials . Then, the most active was chosen and added directly to the filter during the production process . The microbial colonization of treated and untreated filter media was assessed at different working times for different incubation times by stereomicroscope and scanning electron microscope analysis . Some of the antimicrobial agents analysed were more active against microbial test strains and compatible with the production process of the filter media . Filter sections analysis of treated filter media showed a significantly lower microbial colonization than those untreated, a reduction of species both in density and varieties and of the presence of bacteria and fungal hyphae with reproductive structures . CONCLUSIONS: This study demonstrated the ability of antimicrobial treatments to inhibit the growth of micro-organisms in filter media and subsequently to increase indoor air quality (IAQ), highlighting the value of adding antimicrobials to filter media . SIGNIFICANCE AND IMPACT OF THE STUDY: To make a contribution to solving the problem of microbial contamination of air filters, by demonstrating the efficacy of incorporating antimicrobial agents in the filter media to improve IAQ and health. Crit Rev Food Sci Nutr, 2004, 44(3), 185 - 93 Active food packaging technologies; Ozdemir M et al.; Active packaging technologies offer new opportunities for the food industry, in the preservation of foods . Important active packaging systems currently known to date, including oxygen scavengers, carbon dioxide emitters/absorbers, moisture absorbers, ethylene absorbers, ethanol emitters, flavor releasing/absorbing systems, time-temperature indicators, and antimicrobial containing films, are reviewed . The principle of operation of each active system is briefly explained . Recent technological advances in active packaging are discussed, and food related applications are presented . The effects of active packaging systems on food quality and safety are cited. Biochim Biophys Acta, 2004 Jun 28, 1657(1), 1 - 22 The NADPH oxidase of professional phagocytes--prototype of the NOX electron transport chain systems; Cross AR et al.; The NADPH oxidase is an electron transport chain in "professional" phagocytic cells that transfers electrons from NADPH in the cytoplasm, across the wall of the phagocytic vacuole, to form superoxide . The electron transporting flavocytochrome b is activated by the integrated function of four cytoplasmic proteins . The antimicrobial function of this system involves pumping K+ into the vacuole through BKCa channels, the effect of which is to elevate the vacuolar pH and activate neutral proteases . A number of homologous systems have been discovered in plants and lower animals as well as in man . Their function remains to be established. Arch Pharm (Weinheim), 2004 Jul, 337(7), 402 - 10 Synthesis and antimicrobial activity of new 2-{p-substituted-benzyl}-5-{substituted-carbonylamino}benzoxazoles; Yildiz-Oren I et al.; A series of 23 new 2-{p-substituted-benzyl}-5-{p-substituted-phenyl/benzyl-carbonylamino}benzoxazole derivatives has been synthesized by reacting 5-amino-2-{p-substituted-benzyl}benzoxazoles with the appropriate carboxylic acid chlorides . The structures of the synthesized compounds were confirmed by IR and (1)H-NMR spectral data . Antimicrobial activities of the compounds were investigated using the twofold serial dilution technique against two gram-positive and two gram-negative bacteria and three Candida species in comparison with standard drugs . Microbiological results indicated that the newly synthesized 2-{p-substituted-benzyl}-5-{p-substituted-phenyl/benzyl-carbonylamino}benzoxazole derivatives (3-25) possessed a broad spectrum of activity, showing MIC values of 6.25-200 microg/mL against the gram-positive and gram-negative microorganisms tested . Moreover, they showed significant antifungal activity with MIC values of 3.12-100 microg/mL against the Candida species tested . Especially, with a MIC value of 3.12 microg/mL, 2-benzyl-5-{p-bromobenzyl-carbonylamino}benzoxazole 9 displayed the same activity against C . glabrata as the standard drug myconazol. Arch Pharm (Weinheim), 2004 Jul, 337(7), 371 - 5 New total synthesis of niphatesine C and norniphatesine C based on a Sonogashira reaction; Krauss J et al.; The pyridine alkaloid niphatesine C and its analogue norniphatesine C were prepared in a short and efficient way starting from commercially available 3-iodopyridine and undec-10-yn-1-ol using a Sonogashira reaction as the key step . The resulting alkylpyridines were tested for antimicrobial activity against several bacteria and fungi . The cytotoxic activities were determined in the MTT assay against HL 60 cells. Liver Transpl, 2004 Jul, 10(7), 817 - 27 The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: a systematic review and meta-analysis; Safdar N et al.; Selective digestive decontamination (SDD) refers to the use of antimicrobials to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract to prevent infections caused by these organisms . Liver transplant patients are highly vulnerable to bacterial infection particularly with gram-negative organisms within the first month after transplantation, and SDD has been proposed as a potential measure to prevent these infections . However, the benefit of this procedure remains controversial . We undertook a systematic review and meta-analysis to determine whether SDD is beneficial in reducing infections overall and those caused by gram-negative bacteria in patients following liver transplantation . All studies that evaluated the efficacy of SDD in liver transplant patients were included . Randomized trials that included liver transplant patients given SDD versus either placebo or no treatment or minimal treatment (e.g., oral nystatin alone), and that provided adequate data to calculate a relative risk ratio, were included in the meta-analysis . Our review shows that most studies found SDD to be effective in reducing gram-negative infection . The nonrandomized and uncontrolled trials also showed benefit with SDD in reducing overall infection; however, the effect on overall infection was limited in the 4 randomized trials, in which the pooled relative risk was 0.88 (95% CI, 0.7-1.1), indicating no statistically significant reduction in infection with the use of SDD . The summary risk ratio for the association between SDD and gram-negative infection was 0.16 (95% CI, 0.07-0.37), indicating an 84% relative risk reduction in the incidence of infection caused by gram-negative bacteria in patients receiving SDD in randomized trials . In conclusion, the available literature supports a b