Antimicrobial

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 beneficial effect of SDD on gram-negative infection following liver transplantation; however, the risk of antimicrobial resistance must be considered . Larger multicenter randomized trials in this patient population to assess the effect of SDD in reducing infection and mortality, while assessing the risk of antimicrobial resistance, are needed.

J Infect, 2004 Aug, 49(2), 88 - 93
The immunostimulating and antimicrobial properties of lithium and antidepressants; Lieb J; Eicosanoids are products of arachidonic acid (AA), an essential fatty acid . They include prostaglandins (PGs), prostacyclin (PGI2), thromboxanes (TXs), leukotrienes (LTs) and hydroxy fatty acids . AA is derived enzymatically from membrane phospholipids and to a lesser extent the diet . Eicosanoids self-regulate every cell, including those synthesizing serotonin, norepinephrine and dopamine and those subserving immune function, such as T-cells, B-cells, natural killer cells, macrophages, monocytes and dendritic cells . There is objective evidence that prostaglandins regulate the physiology of the hypothalamic-pituitary-adrenal axis (HPA) . Elucidation of the structure and metabolic pathways of eicosanoids galvanized researchers into illuminating their role in physiology, pathology and pharmacology . Striking contradictions arose: eicosanoids were shown to activate and suppress microorganisms, potentiate and suppress immunity and possess pro- and anticancer properties . As prostaglandins are the most heavily studied eicosanoids in the context of mood and immunity I will focus on them in this article . I will present evidence of the immunostimulating and antimicrobial properties of lithium and antidepressants and propose that these properties are linked to the antiprostaglandin actions of these compounds.

Biochemistry, 2004 Jul 13, 43(27), 8846 - 57
Kinetics of dye efflux and lipid flip-flop induced by delta-lysin in phosphatidylcholine vesicles and the mechanism of graded release by amphipathic, alpha-helical peptides; Pokorny A et al.; Delta-lysin is a 26-residue, amphipathic, alpha-helical peptide of bacterial origin . Its specificity is to some extent complementary to that of antimicrobial peptides . Therefore, understanding its mechanism is important for the more general goal of understanding the interaction of amphipathic peptides with membranes . In this article, we show that delta-lysin induces graded efflux of the contents of phosphatidylcholine vesicles . In view of this finding, carboxyfluorescein efflux kinetics were re-examined . In addition, peptide-induced lipid flip-flop was directly measured using fluorescence energy transfer between two lipid fluorophores initially placed on opposite leaflets of the bilayer . Carboxyfluorescein efflux and lipid flip-flop occur with essentially identical rate constants . On the basis of a detailed, quantitative analysis of the kinetics of peptide-vesicle interactions, we conclude that the peptide translocates across the bilayer as a small, transient aggregate, most likely a trimer . Dye efflux and lipid flip-flop occur concomitantly with the transient peptide-induced perturbation of the membrane . The experimental data are interpreted by comparing the predictions of the available models for the mechanism of action of amphipathic alpha-helical peptides . We demonstrate how the combination of the quantitative kinetic analysis, graded efflux, and reversibility of the peptide-vesicle interaction can be used to reject several models for this particular peptide . Two models are compatible with the data, the toroidal pore model and the sinking raft model . On the basis of the small aggregate size, a trimer, the latter appears to be more plausible . Some significant modifications are introduced in the sinking raft model to take into account the new finding of graded dye release . Furthermore, we present an explanation for the phenomenon of graded release in general, which, contrary to all-or-none efflux, has not been well-understood.

Hernia . 2004 Jul 3; {Epub ahead of print}
Laparoscopic incisional and ventral hernia repair: Complications-how to avoid and handle; LeBlanc KA; Complications will occur with any operative procedure . The possibility of this must be considered for laparoscopic incisional and ventral hernia repair (LIVH) as well . The most commonly reported of these include: intraoperative intestinal injury (1-3.5%), infection involving the prosthetic biomaterial (0.7-1.4%), seromas (2.6-100%), postoperative ileus (1-8%), and persistent postoperative pain (1-2%) . The incidence of enterotomy can be reduced by careful dissection and judicious use of any energy source . Infection can be minimized by the use of perioperative antibiotics, an antimicrobially impregnated biomaterial, and careful manipulation of the prosthesis during the procedure . Seromas are so common that they should be expected but can be decreased by the use of a postoperative abdominal binder . Aspiration will be necessary in a few instances . Similarly, ileus is expected when there is significant bowel dissection and bleeding . Early ambulation and standard use of postoperative bowel care will aid in the treatment of this problem . Persistent pain will generally occur at the site of a transfascial suture . It cannot be predicted or prevented with certainty . When it occurs, local injection with bupivacaine, steroids, or non-steroidal agents will help, but occasionally, removal of the offending suture(s) will be required . The average recurrence rate for LIVH is approximately 5.6% in the literature . Rates as high as 15.7%, however, have been reported . Recurrence will be increased by inadequate prosthetic overlap of the fascial defect, infection that involves the biomaterial, which then requires its removal, and lack of the use of transfascial sutures . To prevent these risks, the surgeon must assure that there is at least a 3-cm overlap of all portions of the hernia defect and insist that sutures are used at 5-cm intervals to fix the biomaterial . Infection that requires explantation of the patch will generally result in recurrence, as this must be repaired primarily . Alternatively, the use of a collagen prosthesis may allow immediate repair, but this is associated with a high failure rate . A staged repair will be necessary in the future in most patients.

Saudi Med J, 2004 Jul, 25(7), 837 - 42
The crisis of antibiotic-resistance in bacteria; El-Tahawy AT; Significant increases in the prevalence of resistance to antibiotics have been observed in common pathogen of humans worldwide . The consequences of the appearance and spread of antimicrobial resistance have included increasing morbidity, mortality, and cost of health care . The increasing use of antimicrobial agents promotes the appearance and spread of bacterial resistance . Strict clinical guidelines on antibiotic prescribing and firm guidance on the optimum length of treatment is required . These strategies can be utilized as a part of a multidisciplinary approach to limit the appearance and dissemination of antimicrobial resistance, in addition to, surveillance of antibiotic resistance rates both locally and nationally.

Nat Immunol, 2004 Aug, 5(8), 836 - 43 Epub 2004 Jul 04.
Increased diversity of intestinal antimicrobial peptides by covalent dimer formation; Hornef MW et al.; Antimicrobial peptides are essential effector molecules of the innate immune system . Here we describe the structure, function and diversity of cryptdin-related sequence (CRS) peptides, a large family of antimicrobial molecules . We identified the peptides as covalent dimers in mouse intestinal tissue in amounts comparable to those of Paneth cell-derived enteric alpha-defensins . CRS peptides caused rapid and potent killing of commensal and pathogenic bacteria . The CRS peptides formed homo- and heterodimers in vivo, thereby expanding the repertoire of antimicrobial peptides and increasing the peptide diversity of Paneth cell secretions . CRS peptides might therefore be important in the maintenance of the microbial homeostasis within the intestinal tract.

Presse Med, 2004 Apr 24, 33(8), 522 - 9
{Lung diseases in the elderly . Assessment of guidelines for the probabilistic prescription of antibiotics in a department of geriatric care}; Huvent-Grelle D et al.; OBJECTIVE: We developed a prescribing guideline containing recommendations for the initial empirical antibiotic therapy in community or nosocomial pneumonia . The aim of the present study was to examine the impact of this measure . METHOD: The prescribing guideline was implemented in May 1999 . We retrospectively reviewed the charts of all patients>65 years with community-, or nursing home- or hospital-acquired pneumonia hospitalised in our department of acute geriatric care between May 1999 and November 2000 . The criteria assessed were: consistence with the guideline, clinical effectiveness within 72 hours, adequation with the isolated germs and intra-hospital mortality . RESULTS: Data were collected on 112 patients (63 women et 49 men; mean age=80 +/- 8 Years) . The pneumonia was community-acquired in 52 cases (46%), nursing home acquired in 25 cases (22%) and hospital-acquired in 35 cases (31%) . Antibiotic prescription was consistent with the guideline in 64 cases (57%) . When the antibiotic therapy was consistent, the patients were more likely to improve within 72 hours (45/64 versus 23/48; p=0.01) . Despite a tendency, the number of antimicrobial treatments adapted to the isolated microorganisms was not significantly higher in the consistent group (22/36 adapted treatments versus 10/20) . The intra-hospital mortality (25%) was similar in the two groups consistent and not consistent with the guideline . SARM was the most frequent multiresistant bacteria that was isolated . CONCLUSION: The use of a prescribing guideline might improve the efficiency of empirical probabilistic antibiotic therapies . The impact of the guideline use on overall antibiotic costs and microbiological flora remains to be determined.

J Biol Chem, 2004 Sep 10, 279(37), 38854 - 60 Epub 2004 Jul 02.
Regulation of antiprotease and antimicrobial protein secretion by airway submucosal gland serous cells; Joo NS et al.; Airway submucosal gland serous cells express the cystic fibrosis transmembrane conductance regulator (CFTR) and secrete antimicrobial, anti-inflammatory, and antioxidant molecules . In cystic fibrosis, diminished gland secretion may impair innate airway host defenses . We used Calu-3 cells as a serous cell model to study the types of proteins released, the pathways that release them, and the possible involvement of CFTR activity in protein release . Many proteins were secreted constitutively into the apical fluid and showed increased release to agonists . We identified some of them by high pressure liquid chromatography-mass spectrometry and reverse transcriptase PCR, including lysozyme, siderocalin (the protein NGAL), which inhibits bacterial growth by binding iron-containing siderophores, HSC-71, which is thought to have anti-inflammatory properties, and the serine protease inhibitors alpha-1-antitrypsin and alpha-1-antichymotrypsin, which may function as antimicrobials as well as play a potential role in diminishing the activation of epithelial Na(+) channels by serine proteases . We used an enzyme-linked immunosorbent assay to quantify lysozyme secretion by Calu-3 cells in response to various agonists and inhibitors . Forskolin increased the lysozyme secretion rate (J(lyz)) from 32 to 77 ng/hr/cm(2) (n = 36, p < 0.005) . Thapsigargin increased J(lyz) from 40 to 63 ng/h/cm(2) (n = 16, p < 0.005), and forskolin plus thapsigargin further increased the forskolin-stimulated J(lyz) by 48% (n = 9, p < 0.05) . 1-Ethyl-benzimidazolinone and carbachol were less effective . Glibenclamide inhibited basal and stimulated J(lyz), but clotrimazole was without effect . CFTR(inh)172 caused a small (15%) but significant inhibition of forskolin-stimulated J(lyz) without affecting basal J(lyz) . Thus, Calu-3 cells secrete diverse proteins that in aggregate would be expected to suppress microbial growth, protect the airways from damage, and limit the activation of epithelial Na(+) channels via serine proteases.

J Ethnopharmacol, 2004 Aug, 93(2-3), 279 - 84
Studies on the analgesic and anti-inflammatory effects of Sideritis candicans Ait . var . eriocephala Webb aerial part; Hernandez-Perez M et al.; Different extracts and fractions from Sideritis candicans Ait . var . eriocephala Webb aerial part were investigated for their analgesic, anti-inflammatory and antimicrobial activities in mice . Results indicated that the extracts assayed showed anti-nociceptive activities because they were able to reduce the nociceptive response to chemical pain stimuli, such as in the acetic acid-induced writhing test . Moreover the extracts also possessed anti-inflammatory activity against carrageenan-induced paw oedema and TPA-induced ear oedema, being the chloroform fraction the most active . Further fractionation and analysis of this fraction revealed that the analgesic and anti-inflammatory activities found could be related in part to the presence of phytosterols, alpha and beta amyrin triterpenic derivatives and ent-kaurene type diterpenes in this species, since some of these compounds are endowed with these activities.

Chemosphere, 2004 Aug, 56(7), 667 - 76
Evaluation of manometric respiration tests to assess the effects of veterinary antibiotics in soil; Vaclavik E et al.; Extensive use of antimicrobials in veterinary medicine results in environmental exposure . Of major concern are microbial effects; including effects on nutrient soil cycles and antibiotic resistance . There is a need to assess the effects of these compounds in the environment . The application of standardized guidelines is relevant in studying many compounds . However there is a lack of special test methods designed for antibiotics . We validate manometric test flasks using glucose and a recalcitrant herbicide . The suitability of these tests for studying antibacterial agents is then investigated using two target functions (aerobic biodegradation and carbon transformation) . Compound stability is quantified using HPLC techniques . Effects on total soil respiration in the biodegradation test are immediate and differ significantly from background . We show that compounds do not function as substrates, so effects are due to other soil processes, correlate well to sorption characteristics and are not dose dependent . This test provides details of relative antimicrobial potency towards soil microorganisms and can be used to rank compounds . However the test does not provide details on the nature or extent of specific microbial effects . In contrast, the carbon transformation test is more specific and provides a reproducible indication of dose effect relationships, which is more suitable in assessing the effects of these compounds in the environment . Presently, standard guidelines do not take into account the normal input of antibiotics into soils via contaminated sludge or manure . This should be corrected in future guidelines as these inputs alter microbial composition, organic matter, ionic strength and pH affect sorption and overall impact the test results.

Mol Ther, 2004 Jul, 10(1), 76 - 85
FGF-7 expression enhances the performance of bioengineered skin; Erdag G et al.; To improve the performance of bioengineered skin, we used a recombinant retrovirus encoding FGF-7 to modify diploid human keratinocytes genetically . Control or FGF-7-expressing keratinocytes were seeded onto acellular human dermis to form bioengineered skin . Gene-modified skin secreted significant levels of FGF-7 and formed a thicker and hyperproliferative epidermis with about four times the number of cells per square centimeter . Secretion of an endogenous trophic factor, VEGF, was increased approximately 5-fold . Migration of FGF-7-expressing keratinocytes was stimulated as was the self-healing of bioengineered skin expressing FGF-7 . When tested in a bacterial infection model, the antimicrobial properties of FGF-7-expressing skin were increased >500-fold against both gram-negative and gram-positive bacteria . After transplantation to full-thickness wounds on athymic mice, skin expressing FGF-7 was revascularized more rapidly . These results demonstrate that genetic modification can be used to enhance performance and that expression of FGF-7 augments several properties important to the wound-healing properties of bioengineered skin.

Eur J Biochem, 2004 Jul, 271(14), 2984 - 90
Apolipoproteins A-I and A-II are potentially important effectors of innate immunity in the teleost fish Cyprinus carpio; Concha MI et al.; We have previously shown that high density lipoprotein is the most abundant protein in the carp plasma and displays bactericidal activity in vitro . Therefore the aim of this study was to analyze the contribution of its principal apolipoproteins, apoA-I and apoA-II, in defense . Both apolipoproteins were isolated by a two step procedure involving affinity and gel filtration chromatography and were shown to display bactericidal and/or bacteriostatic activity in the micromolar range against Gram-positive and Gram-negative bacteria, including some fish pathogens . In addition, a cationic peptide derived from the C-terminal region of carp apoA-I was synthesized and shown to possess antimicrobial activity (EC(50) = 3-6 micro m) against Planococcus citreus . This peptide was also able to potentiate the inhibitory effect of lysozyme in a radial diffusion assay at subinhibitory concentrations of both effectors . Finally, limited proteolysis of HDL-associated apoA-I with chymotrypsin in vitro was shown to generate a major truncated fragment, which indicates that apoA-I peptides liberated in vivo through a regulated proteolysis could also be involved in innate immunity.

Mol Cells, 2004 Jun 30, 17(3), 469 - 76
Structure-activity relationships of antimicrobial peptides from the skin of Rana esculenta inhabiting in Korea; Won HS et al.; The anuran (frogs and toads) skin is a rich source of antimicrobial peptides that can be developed therapeutically . We searched the skin secretions of Korean Rana esculenta for antimicrobial peptides, and isolated two cationic peptides with antimicrobial activity and little hemolytic activity: a 46-residue peptide of the esculentin-1 family and a 24-residue peptide of the brevinin-1 family . Their sequences showed some differences from the esculentins-1 and brevinins-1 of European Rana esculenta, indicating that sequence diversification of anuran skin antimicrobial peptides can arise from differences in habitat as well as from species differences . The 46-residue peptide named esculentin-1c had broad antimicrobial activity, while the 24-residue peptide named brevinin-1Ed exhibited limited activity . The solution structure of brevinin-1Ed was in good agreement with that of other brevinin-1-like peptides, with an amphipathic alpha-helix spanning residues 3-20, stabilized in membrane-mimetic environments . The weak bioactivity of brevinin-1Ed was attributable to the unusual presence of an anionic amino acid in the middle of the helical hydrophilic face . This report contributes to world-wide investigations of the structure-activity relationships and evolutional diversification of anuran-skin antimicrobial peptides.

Vet Pathol, 2004 Jul, 41(4), 326 - 37
Gene expression and antimicrobial activity of bovine macrophages in response to Mycobacterium avium subsp . paratuberculosis; Weiss DJ et al.; We evaluated gene expression and antimicrobial responses of bovine monocyte-derived macrophages incubated with Mycobacterium avium subsp . paratuberculosis (M . a . ptb), the causative agent of Johne's disease . Gene expression was evaluated by the use of human noncompetitive high-density oligonucleotide microarrays . Bovine messenger RNA hybridized with 14.2-18.2% of the 12,600 oligonucleotide probe sets . When macrophages incubated with M . a . ptb were compared with nonactivated control macrophages, macrophages activated by addition of interferon-gamma and lipopolysaccharide, and macrophages incubated with Mycobacterium avium subspecies avium (M . a . a), 47, 79, and 27 genes, respectively, were differentially expressed . Differential expression of six of these genes was confirmed using reverse transcriptase polymerase chain reaction . Several functional assays were performed to evaluate the potential relevance of differentially expressed genes to host defense . Macrophages phagocytizing M . a . a had a greater capacity to kill the organisms and to acidify phagosomes and a greater degree of apoptosis than did macrophages incubated with M . a . ptb . The results of these studies indicate that multiple genes and metabolic pathways are differentially expressed by macrophages ingesting mycobacterial organisms . Although the intracellular fate of mycobacterial organisms appears to be dependent on a complex interaction between macrophage and organism, phagosome acidification and apoptosis may play central roles in organism survival.

Reproduction, 2004 Jul, 128(1), 117 - 26
Evaluation of antimicrobial peptide nisin as a safe vaginal contraceptive agent in rabbits: in vitro and in vivo studies; Reddy KV et al.; In the midst of the global epidemics of both unwanted pregnancies and sexually transmitted infections (STIs), options that provide protection are ideal . In the present study, nisin, a known antimicrobial peptide, was evaluated for safety and contraceptive potential in vitro and in vivo in the rabbit . A concentration of 400 microg nisin per ml was found to be spermicidal in vitro, and the effect was dose and time dependent . In vivo studies indicated that intravaginal application of 1 mg nisin blocked conception in rabbits . Repeated application of nisin (50 mg/animal per day) in rabbits for 14 consecutive days did not cause local inflammation or damage to the vaginal epithelium . In addition, the rate of diffusion of nisin into the blood via the vaginal mucosal epithelium, and its clearance from the circulation was found to be rapid . No treatment-related changes were observed in the reproductive performance of rabbits after cessation of treatment . Furthermore, no changes were observed in the gestation period, subsequent growth and survival of neonates in these animals . When male rats were given nisin orally for 13 consecutive weeks, no effect was observed on reproductive performance . The number of pups born, survival and growth of pups were unaltered . The affinity studies of nisin revealed that spermatozoa are more susceptible to nisin than red blood cells and vaginal epithelial cells . We suggest that nisin with spermicidal and antimicrobial properties could serve as a safe vaginal contraceptive for future therapeutic interventions in STIs.

Pediatrics, 2004 Jul, 114(1), e96 - 101
Azithromycin is as effective as and better tolerated than erythromycin estolate for the treatment of pertussis; Langley JM et al.; OBJECTIVE: Although universal immunization against Bordetella pertussis (whooping cough) infection has resulted in dramatic reductions in the incidence of pertussis, outbreaks continue to occur in countries with excellent vaccine coverage . Treatment of infection may ameliorate symptom severity during the catarrhal phase of pertussis but has no effect on established paroxysms, emesis, or apnea if given during the paroxysmal or convalescent phases . Erythromycin, recommended for treatment of pertussis to prevent transmission of infection, is poorly tolerated because of gastrointestinal side effects . We compared the safety and efficacy of erythromycin with azithromycin for treatment of pertussis in a large, randomized, controlled trial that enrolled children from primary care practices in 1 American and 11 Canadian urban centers . METHODS: Children who were 6 months to 16 years of age and had cough illness that was suspected to be or was culture confirmed as pertussis were randomized to azithromycin (10 mg/kg on day 1 and 5 mg/kg on days 2-5 as a single dose) or erythromycin estolate (40 mg/kg/day in 3 divided doses for 10 days) with stratification by center . The primary outcome measure was bacteriologic cure of infection as determined by cultures of nasopharyngeal aspirates . Culture-positive participants had a second aspirate collected at the end of therapy (days 5-7 for azithromycin, days 10-12 for erythromycin) and 1 week after therapy . Bacteriologic cure was defined as negative cultures at the end of therapy . Bacteriologic relapse was defined as a positive culture 1 week after completion of therapy and after a negative end-of-therapy culture . Secondary outcomes were pertussis diagnosed by serology and polymerase chain reaction (PCR), treatment-associated adverse events, compliance, and presence of clinical symptoms at the end of the treatment course . Serology was performed using standard enzyme-linked immunosorbent assay methods . A participant was considered to have pertussis when the PCR was positive or a 4-fold increase in pertussis toxin antibody between baseline and follow-up visits was observed . PCR was performed using a 1046-bp ClaI DNA fragment from B pertussis . Adverse events (nausea, vomiting, diarrhea, any gastrointestinal complaint, or other) were determined by a parent-completed diary that was reviewed with study personnel during study visits . Compliance was measured by review of the parent medication diary during study visits and observation of medication containers by the pharmacist at study completion . Symptoms were determined by history collected by study personnel at enrollment and subsequently from the diary . The design of the study was an equivalence trial, aimed at demonstrating that the bacteriologic failure rates with the 2 therapies did not differ by >8% . For the safety analysis, all participants who received at least 1 dose of study drug were included . In the per-protocol efficacy analysis, all culture-positive participants with end-of-treatment cultures were considered . RESULTS: A total of 477 children were enrolled and randomly assigned to either azithromycin (n = 239) or erythromycin (n = 238) . Of these children, 114 (24%) grew B pertussis from nasopharyngeal specimens (azithromycin group: 58 of 239 {24%}; erythromycin group: 56 of 238 {23%}); these children composed the efficacy cohort for the per-protocol and intention-to-treat analyses . Serology and PCR added 52 children to the number considered to have pertussis for a total of 35% (166 of 477) of all children who presented with cough illness . In the safety analysis (antibiotic side effects, compliance) and comparison of cough symptoms after treatment, all randomized children are reported in their assigned treatment group . At end of therapy, bacterial eradication was demonstrated in all 53 patients in the azithromycin group and all 53 patients in the erythromycin group with follow-up cultures available (eradication 100%; 95% confidence interval {CI}: 93.3-100) . No bacterial recurrence was demonstrated in children with 1 week posttreatment nasopharyngeal cultures available (51 and 53 participants in the azithromycin and erythromycin arms, respectively {0%, 95% CI: 0-7.0; and 0%, 95% CI: 0-6.7}) . No serious adverse events attributable to study drug were observed . Gastrointestinal adverse events were reported less frequently in azithromycin (18.8%; 45 of 239) than in erythromycin estolate (41.2%; 98 of 238) recipients (90% CI on difference: -29.0% to -15.7%) as a result of less nausea (2.9% vs 8.4%; 95% CI: -8.9% to -2.0%), less vomiting (5.0% vs 13.0%; 95% CI: -4.9% to -1.4%), and less diarrhea (7.1% vs 11.8%; 95% CI: -9.0% to -0.3%) . Children who were randomized to azithromycin were much more likely to have complied with antimicrobial therapy over the treatment period . In the azithromycin group, 90% of children took 100% of prescribed doses, whereas only 55% of children in the erythromycin group took 100% of prescribed doses . CONCLUSIONS: In this large, multicenter, randomized trial, we found that azithromycin is as effective as erythromycin estolate for the treatment of pertussis in children . Gastrointestinal adverse events were much more common with erythromycin treatment than azithromycin . Compliance with therapy was markedly better with azithromycin than with erythromycin in this study.

J Antimicrob Chemother, 2004 Aug, 54(2), 306 - 10 Epub 2004 Jul 01.
The relentless rise of resistance?
Wise R.
Antibiotics have undoubtedly made a major contribution to improvements in both human and animal health and welfare . Recent years have brought alarming rises in the prevalence of resistance to some agents among certain groups of bacteria . Concern is growing that therapeutic options will become increasingly limited if resistance rates continue to rise . There is widespread agreement that action is required to reverse or at least slow this process . Necessary steps to manage the situation include better surveillance to assess accurately the extent of problems, more prudent use of the available antibiotics to conserve valuable therapeutic resources and improved infection control to limit the spread of resistant organisms . Achieving these goals will not be possible without government, the medical profession and the public being better informed and educated . Regulatory bodies and the pharmaceutical industry need to work together to ensure a steady supply of new antimicrobials . Our understanding of the processes driving resistance at both the molecular and population levels is advancing . However, the relative contributions of the various uses of antimicrobials to the resistance problem and which will be the most effective containment measures are still hotly debated . Progress is being made, but continued concerted action is necessary if the usefulness of this most important group of therapeutic agents is to be preserved.

DNA Cell Biol, 2004 Jun, 23(6), 341 - 50
Molecular and cellular control of T1/T2 immunity at the interface between antimicrobial defense and immune pathology; Bot A et al.; The immune system evolved to rapidly recognize infectious threats and promptly mobilize cellular effectors to the infection site . Establishment of a robust T1-type immunity is a prerequisite for effective defense against most viruses and intracellular bacteria . However, accumulating evidence shows that T1 and T2 responses during such infections are not mutually exclusive . A possibility may be that the dual T1-T2 nature of antiviral immune responses is merely a byproduct of less than perfect crossregulatory mechanisms . Herein, we discuss molecular and cellular mechanisms of T-cell differentiation along with recent evidence supporting the hypothesis that rather than representing an epiphenomenon, coinduction of virus-specific T2 cells plays a significant homeostatic role . Thus, molecular pathways that regulate IL-4 production during influenza virus infection monitor T1-mediated immune responses in vital organs such as lungs and prevent immune pathology that may otherwise interfere with recovery from disease . Such evidence suggests that coinduction of T2 immunity maintains immune homeostasis during T1-mediated defense reactions . Finally, we outline implications on the earlier concept of T1/T2 dichotomy, supporting a model in which these two subsets, rather than being mutually antagonistic, together facilitate the recovery from infection.

Drug Saf, 2004, 27(9), 671 - 86
Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies; Gavin JR 3rd et al.; BACKGROUND: Recently, clinical data has emerged suggesting that the fluoroquinolone, gatifloxacin, can affect glucose homeostosis through an unknown mechanism . In order to explore the potential effects of moxifloxacin on glucose metabolism in humans, a pooled analysis of phase II/III clinical trials and postmarketing studies was performed and compared with results from an investigation in laboratory animals . METHODS: A pooled analysis of 30 (26 controlled, 4 uncontrolled) oral and two intravenous/oral prospective, controlled phase II/III moxifloxacin studies was performed to evaluate the frequency of hyper- and hypoglycaemic episodes and glucose-related adverse events and adverse reactions (i.e . those considered to be drug related) versus comparator antimicrobials (penicillins, cephalosporins, macrolides, doxycycline, fluoroquinolones) . Similar evaluations were conducted on data pooled from five postmarketing surveillance studies . In addition, potential effects of supratherapeutic doses of moxifloxacin on blood glucose and plasma insulin levels in fed and fasted rats were assessed in comparison with those of gatifloxacin, levofloxacin and glibenclamide (glyburide) . RESULTS: The phase II/III database was comprised of 14,731 patients (8474 moxifloxacin, 6257 comparator antimicrobial).There were no drug-related hypoglycaemic adverse events reported for moxifloxacin in either the oral or intravenous/oral database . Two drug-related hypoglycaemic adverse events were reported in the oral comparator group, both following administration of levofloxacin and both of mild severity; one drug-related hypoglycaemic adverse event was reported in the intravenous/oral comparator group after trovafloxacin administration . Drug-related hyperglycaemic adverse events were reported in seven (<0.1%) moxifloxacin and 1 (<0.1%) comparator-treated patients in the oral study database, none of these cases were considered serious and six of the seven moxifloxacin cases were graded as mild and required no countermeasures . There were no cases of drug-related hyperglycaemic events in any patient enrolled in the intravenous/oral studies . Coadministration of oral antidiabetic drugs with moxifloxacin or comparator antimicrobials did not change the rate of blood glucose increases or decreases in diabetic patients . Data from five moxifloxacin postmarketing studies (46 130 subjects) reported no episodes of hypoglycaemia and two non-drug-related hyperglycaemic episodes . Data from animal studies revealed that supratherapeutic doses of moxifloxacin and levofloxacin did not affect blood glucose or plasma insulin levels in both fed and fasted rats, whereas gatifloxacin decreased both blood glucose and plasma insulin in a dose-dependent manner in fed rats only . The reference compound glibenclamide increased insulin and decreased glucose levels as expected . CONCLUSIONS: Hyperglycaemic or hypoglycaemic adverse reactions were reported rarely in studies with oral or sequential intravenous/oral moxifloxacin, and incidence was comparable in moxifloxacin and comparator groups . Changes in glucose metabolism were also similar in diabetic patients treated with moxifloxacin compared with those patients without diabetes mellitus . This comprehensive analysis of the datapool for moxifloxacin phase II/III clinical trials and postmarketing studies suggests that moxifloxacin administration has no clinically relevant effect on blood glucose homeostasis.

Planta Med, 2004 Jun, 70(6), 515 - 9
Chemical analysis and antimicrobial activity of Greek propolis; Melliou E et al.; One new 2,3-dihydroflavone derivative, 7- O-prenylstrobopinin, and 25 known diterpenes and phenolic compounds were identified from the n-butanol extract of Greek propolis . This is the first time that diterpenes have been isolated from propolis of European origin, while six of the known compounds are reported as propolis constituents for the first time . The structures of the isolated compounds were determined by spectroscopic methods, mainly by the concerted application of 1D, 2D NMR techniques (HMQC, HMBC, NOESY) and mass spectrometry . The studied sample and the isolated compounds were tested for their antimicrobial activity against Gram (+/-) bacteria and fungi and five of them exhibited strong activities.

Biol Reprod, 2004 Nov, 71(5), 1484 - 90 Epub 2004 Jun 30.
Antimicrobial activity of human EPPIN, an androgen-regulated, sperm-bound protein with a whey acidic protein motif; Yenugu S et al.; The role of epididymal sperm-binding proteins in reproductive tract immunity is now well recognized in addition to their role in sperm maturation . Spermatozoa acquire forward motility and fertilizing ability during their passage through the epididymis, where they acquire a wide variety of proteins belonging to different classes . Previously, we demonstrated that EPPIN (epididymal protease inhibitor), an androgen-regulated, sperm-binding protein containing protease-inhibitory motifs, is expressed specifically in the testis and epididymis . In the present study, we investigated the antibacterial activity of EPPIN against Escherichia coli and the mechanism of antimicrobial action . EPPIN exhibited dose- and time-dependent antibacterial activity that was relatively insensitive to salt . However, EPPIN lost its antibacterial activity completely on reduction and alkylation of its cysteines, indicating the importance of disulfide bonds for its activity . EPPIN permeabilized the outer and inner membranes of E . coli, which is consistent with its ability to induce striking morphological alterations of E . coli membranes as shown by scanning electron microscopy . EPPIN did not cause disruption of eukaryotic membranes in the rat erythrocyte hemolytic assay . The present results indicate that EPPIN has a role in the innate immune system of human epididymis.

Am J Epidemiol, 2004 Jul 1, 160(1), 46 - 50
Risk factors for enteric perforation in patients with typhoid Fever; Hosoglu S et al.; A case-control study was performed using the records of patients hospitalized for typhoid fever at Dicle University Hospital, Diyarbakir, Turkey, between 1994 and 1998 . Case patients with enteric perforation were compared with control patients with typhoid fever but no enteric perforation . Risk factors for perforation were determined using logistic regression modeling . Forty case patients who had surgery because of typhoid enteric perforation were compared with 80 control patients . In univariate analyses, male sex (p = 0.01), age (p = 0.01), leukopenia (p = 0.01), inadequate antimicrobial therapy prior to admission (p = 0.01), and short duration of symptoms (p = 0.01) were significantly associated with perforation . In multivariate analysis, male sex (odds ratio (OR) = 4.39, 95% confidence interval (CI): 1.37, 14.09; p = 0.01), leukopenia (OR = 3.88, 95% CI: 1.46, 10.33; p = 0.04), inadequate treatment prior to admission (OR = 4.58, 95% CI: 1.14, 18.35; p = 0.03), and short duration of symptoms (OR = 1.22, 95% CI: 1.10, 1.35; p = 0.001) were significant predictors of perforation . A short duration of symptoms, inadequate antimicrobial therapy, male sex, and leukopenia are independent risk factors for enteric perforation in patients with typhoid fever .

J Coll Physicians Surg Pak, 2004 Feb, 14(2), 119 - 21
Odontogenic cervical necrotizing fasciitis; Ashar A; Two cases of cervical necrotizing fasciitis, secondary to dental infection, are presented . It is a potentially life-threatening severe mixed infection with rapidly progressive inflammation and necrosis of the fascia, muscle and fat . Laboratory and CT features are described . CT scan was also useful for progress monitoring during the treatment . Both cases were complicated by mediastinitis with pleural effusions . A successful non-fatal outcome was achieved following multiple surgical interventions, aggressive culture based antimicrobial therapy, multi-specialty approach and intensive supportive care of the patients.

Anal Chem, 2004 Jul 1, 76(13), 3764 - 9
Spontaneous integration of transmembrane peptides into a bacterial magnetic particle membrane and its application to display of useful proteins; Tanaka T et al.; An antimicrobial peptide, temporin L, and its derivative (TL-A2) were employed as anchor peptides and displayed streptavidin on a bacterial magnetic particle (BMP) membrane . The ribotoxin L3 loop (L3) and the arginine-chain peptide (R(12)), which are carrier peptides permeable to eukaryotic cell membranes, were also used . The peptides were labeled with a fluorescent dye, 4-fluoro-7-nitrobenzofurazan (NBD), at the N-terminal region (NBD-peptides) and mixed with BMPs . A specific integration of NBD-temporin L into a BMP membrane was observed . The basic amino acids in temporin L played an important role in the integration into BMPs . Biotin conjugated to the N-terminus of temporin L was integrated into a BMP membrane . The C-terminus of temporin L was incorporated into a BMP membrane, and the N-terminus was located on the BMP membrane surface . The present study shows that temporin L is a stable molecular anchor on BMPs by the binding of soluble protein to the N-terminus.

No Shinkei Geka, 2004 Apr, 32(4), 373 - 7
{A case with surgical repair for delayed occult cerebrospinal fluid rhinorrhea presented as meningitis fourteen years after blunt head trauma}; Kawamoto H et al.; We describe a case of a 34-year-old woman in whom delayed occult cerebrospinal fluid rhinorrhea presented as meningitis . Removal of an implanted shunt system and surgical repair of the fistula were required . The cerebrospinal fluid fistula was located in the left frontoethmoidal region . Fourteen years previously, the patient had been treated successfully for injury to the left internal carotid artery in a motor vehicle collision, by clipping and by implantation of ventriculoperitoneal and subduralperitoneal shunts to reverse the associated hydrocephalus . To prevent the spread of intracranial infection, we immediately removed the implanted shunt system and followed this by placement of lumbar drainage . After complete resolution of meningitis in response to antimicrobial agents, we performed surgical repair of the fistula . Shunt reconstruction was not required . The patient was discharged with good performance status . This case illustrates the point that effective treatment of meningitis is greatly facilitated by timely removal of associated foreign material.

Clin Infect Dis, 2004 Jun 15, 38(12), 1706 - 15 Epub 2004 May 26.
Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project; Bratzler DW et al.; In January 2003, leadership of the Medicare National Surgical Infection Prevention Project hosted the Surgical Infection Prevention Guideline Writers Workgroup (SIPGWW) meeting . The objectives were to review areas of agreement among the most-recently published guidelines for surgical antimicrobial prophylaxis, to address inconsistencies, and to discuss issues not currently addressed . The participants included authors from most of the groups that have published North American guidelines for antimicrobial prophylaxis, as well as authors from several specialty colleges . Nominal group process was used to draft a consensus paper that was widely circulated for comment . The consensus positions of SIPGWW include that infusion of the first antimicrobial dose should begin within 60 min before surgical incision and that prophylactic antimicrobials should be discontinued within 24 h after the end of surgery . This advisory statement provides an overview of other issues related to antimicrobial prophylaxis, including specific suggestions regarding antimicrobial selection.

Ann Pharmacother, 2004 Sep, 38(9 Suppl), S19 - 23 Epub 2004 Jun 29.
Short-duration therapy for respiratory tract infections; Goff DA; Antimicrobial therapy for community-acquired respiratory tract infections (CARTIs) must be of sufficient duration to result in clinical cure and bacterial eradication . Elimination of the causative bacteria may prevent disease progression, relapse, or recurrence while minimizing the risk for emergence of resistant bacterial strains . Standard 10-day courses of antibiotic therapy often are not completed by patients . This may decrease the likelihood of bacterial eradication and contribute to increased selection of resistant organisms . The ideal antimicrobial agent for the treatment of CARTIs would have an appropriate pharmacokinetic/pharmacodynamic profile for short-course therapy (eg, 5 days) without loss of either clinical or bacteriologic efficacy . Short-course therapy for CARTIs (such as acute bacterial maxillary sinusitis, acute exacerbations of chronic bronchitis, community-acquired pneumonia) has been demonstrated to be effective with antibiotics from several different classes, including the ketolide antimicrobials.

Ann Pharmacother, 2004 Sep, 38(9 Suppl), S14 - 8 Epub 2004 Jun 29.
The importance of appropriate antimicrobial dosing: pharmacokinetic and pharmacodynamic considerations; Preston SL; The increasing antimicrobial resistance of common respiratory pathogens has led to a reevaluation of the selection of antimicrobial dosing regimens in terms of their pharmacokinetic (PK) and pharmacodynamic (PD) properties . Pharmacokinetics, when considered as part of a specific dosing regimen, can help determine the time course of drug concentrations in the serum, tissues, body fluids, and at the site of infection . Pharmacodynamics provides surrogate markers for clinical and bacteriologic efficacy based on the relationships between the serum and tissue concentrations of selected antimicrobial agents relative to the mean inhibitory concentrations of causative bacteria over time . Ultimately, the interrelationships between PK and PD parameters measured for standard dosing regimens determine the time course of the drug's concentration at the site of infection and the impact of the agent's bacteriologic and clinical efficacy . In this review, the distinctive patterns of antimicrobial activity based on PK/PD parameters are discussed . Various antibiotics and bacterial pathogens are used as models to demonstrate the utility of PK/PD parameters in predicting the in vivo efficacy of antimicrobial therapy . The use of computer modeling with Monte Carlo population simulations can further enhance the predictability of antimicrobial efficacy when using PK/PD parameters . This article also provides a reevaluation of bacterial susceptibility breakpoints defined by the National Committee for Clinical Laboratory Standards contrasted with the use of PK/PD parameters.

Toxicon, 2004 Jul, 44(1), 67 - 74
Structural and biological characterization of two novel peptides from the venom of the neotropical social wasp Agelaia pallipes pallipes; Mendes MA et al.; The venom of the neotropical social wasp Agelaia pallipes pallipes was fractionated by RP-HPLC resulting in the elution of seven fractions; the last two were re-fractionated under RP-HPLC by using isocratic elution conditions and the purity of the fractions were confirmed by using ESI-MS analysis . Both fractions are constituted of peptide components, which were sequenced by Edman degradation chemistry, resulting in the following sequences: Protonectin I-L-G-T-I-L-G-L-L-K-G-L-NH(2) . Agelaia-MP I-N-W-L-K-L-G-K-A-I-I-D-A-L-NH(2) . Both peptides are manually synthesized on solid-phase and functionally characterized by using Wistar rats cells . Protonectin is a non-hemolytic chemotactic peptide for polymorphonucleated leukocytes (PMNL), presenting some mast cell degranulating activity and potent antimicrobial action both against Gram-positive and Gram-negative bacteria . Agelaia-MP was characterized as a hemolytic mast cell degranulator toxin, presenting a poor antimicrobial action and no chemotaxis for PMNL.

Mol Microbiol, 2004 Jul, 53(1), 1 - 8
Euroconference on the Biology of Type IV Secretion Processes: bacterial gates into the outer world; Llosa M et al.; Type IV secretion systems (T4SSs) mediate both protein and ssDNA secretion from a wide range of bacteria into virtually any cell type or into the milieu . It is this versatility that confers on them the ability to participate in many processes of bacterial life that imply communication with their environment . Type IV secretion systems are involved in horizontal DNA transfer to other bacteria and to plant cells, in DNA uptake from the milieu, in toxin secretion into the milieu, and in the injection of virulence factors into the eukaryotic host cell in a number of mammalian and plant pathogens . Recently, a EuroConference addressed the different aspects of the biology of these transmembrane multiprotein complexes, from the crystal structure of the individual components to the modification that the secreted substrates induce in the recipient cell . Significant progress has been made in the understanding of the molecular architecture and mechanism of secretion . The analysis of protein-protein interactions confirms the role of coupling proteins as substrate recruiters for the transporter . The VirB10 component of the complex has come up as a strong candidate for signal transducer . The wide range of effects on the recipient suggests that many effector proteins are secreted . New effector proteins are being identified for both plant and animal pathogens, as are their targets within the host cells . New T4SS members are being identified that perform novel roles, beyond DNA transfer and virulence, such as establishment of symbiotic processes . Our current knowledge of the Biology of Type IV Secretion Processes increases our ability to exploit them as biotechnological tools or to use them as new targets for inhibitors that could constitute a new generation of antimicrobials in the near future.

Plant J, 2004 Jul, 39(2), 147 - 60
Isolation and characterisation of a class of carbohydrate oxidases from higher plants, with a role in active defence; Custers JH et al.; In a search for novel plant-derived antimicrobial proteins, we screened extracts from salicylic acid (SA)-treated lettuce and sunflower leaves . These extracts displayed very potent antimicrobial activity against a set of phytopathogens . Characterisation of these extracts revealed that in both extracts, proteins of approximately 60 kDa were responsible for the antimicrobial activity . Further characterisation of these proteins and cloning of the respective cDNAs revealed close homology to a range of (plant) oxidases . Dissection of the enzymatic activity of both proteins revealed them to be carbohydrate oxidases (Helianthus annuus carbohydrate oxidase (Ha-CHOX) and Lactuca sativa carbohydrate oxidase (Ls-CHOX)) with broad substrate specificity and with hydrogen peroxide (H(2)O(2)) as one of the reaction products . The sunflower transcript, in addition to being SA inducible, was also inducible by fungal pathogens but not by ethylene and jasmonate . To determine whether Ha-CHOX plays a role in pathogen defence, it was transformed into tobacco and the effect of resistance to Pectobacterium carotovorum ssp . carotovorum was examined . Transgenic plants overexpressing Ha-CHOX displayed enhanced resistance to infection by this pathogen, and the resistance level was proportional to enzyme expression.

Wound Repair Regen, 2004 May-Jun, 12(3), 351 - 8
HB-107, a nonbacteriostatic fragment of the antimicrobial peptide cecropin B, accelerates murine wound repair; Lee PH et al.; Antimicrobial peptides are essential to innate host defense as effectors of pathogen clearance and can modify host cell behaviors to promote wound repair . While these two functions appear interrelated, it is unclear whether the ability to aid in wound repair requires inherent antimicrobial function . We hypothesized that the influence of antimicrobial peptides on wound repair is not dependent on antimicrobial function . To explore this, we analyzed the microbial killing activity of peptide fragments and correlated this with the ability to influence wound repair in mice . HB-107, a peptide lacking antimicrobial activity and originally derived from the antimicrobial cecropin B, showed up to 64 percent improvement in wound repair compared to scrambled peptide and vehicle controls, an effect comparable to treatment with recombinant human platelet-derived growth factor-BB (formulated as Regranex) . Wounds treated with HB-107 showed keratinocyte hyperplasia and increased leukocyte infiltration . Furthermore, HB-107 stimulated interleukin-8 secretion from cultured endothelial cells, an effect that may explain the increase in leukocyte migration . These findings confirm that antimicrobial peptides can function as effectors of cutaneous wound repair . Moreover, this study furthers our understanding of antimicrobial peptides by showing that their wound repair properties can be independent of antimicrobial function.

Swed Dent J Suppl, 2004, (167), 2 - 75
The miswak (chewing stick) and oral health . Studies on oral hygiene practices of urban Saudi Arabians; al-Otaibi M; The miswak, a traditional chewing stick for cleaning teeth, is made from the plant Salvadora persica . For religious and cultural reasons, miswak use is firmly established and widespread in Saudi Arabia and most other Muslim countries . Only recently has scientific evaluation of the miswak been undertaken . The aims of the thesis were: 1) to explore current oral hygiene habits and oral health awareness among urban Saudi Arabians in relation to age, gender and educational level (papers I and II); 2) to compare mechanical plaque removal and gingival health after miswak use and toothbrushing (paper III); 3) to compare the effect of miswak use and toothbrushing on subgingival plaque microflora (paper IV) . In papers I and II, structured interviews were conducted with 1200 regular patients at two centres in the city of Makkah, providing dental care for university and military staff and their families, respectively . Consecutive patients were stratified according to gender and age, into 6 age groups from 10 to 60 years, with 50 male or female subjects in each group at each centre . Oral hygiene habits were correlated with the subjects' age, gender, and educational levels and analysed statistically by a generalized linear model and ANOVA . In papers III and IV, the subjects comprised 15 healthy Saudi Arabian male volunteers aged 21 to 36 years, attending the Dental Center at Al-Noor Specialist Hospital in Makkah City . A single-blind, randomised crossover design was used . The Turesky modified Quigley-Hein plaque and Loe-Silness gingival indices and digital photographs of plaque distribution were recorded in Paper III and in Paper IV plaque was sampled for DNA-testing . Inhibition zones around miswak material were examined on agar plates with Actinobacillus actinomycetemcomitans and the leukotoxicity of this bacterium was analysed in a bioassay with macrophages +/- miswak extracts (paper IV) . In papers I and II, 73% of the subjects used a toothbrush and 65% used a miswak daily . There were significant differences between genders and age groups, and between the centres . Regular miswak use was more prevalent among men (p < 0.01), while women used a toothbrush more often than a miswak (p < 0.05) . For the majority (88%) of the individuals, oral hygiene began late, after the age of 7 yrs . Oral hygiene habits were strongly correlated to educational level (p < 0.001) . The miswak was preferred by less educated people . Tooth brushing started earlier among the better educated (p < 0.001) . In paper III, compared to tooth brushing, use of the miswak resulted in significant reductions in plaque (p < 0.001) and gingival (p < 0.01) indices . In paper IV, A . actinomycetemcomitans was significantly reduced by miswak use (p < 0.05) but not by tooth brushing . These results were supported by the in vitro observations that extracts from S . persica interfered with growth and leukotoxicity of A . actinomycetemcomitans . It was concluded that oral hygiene practice is introduced very late, is strongly correlated to educational level, and that more women prefer toothbrushing to miswak use . It was further concluded that miswak use was at least as effective as toothbrushing for reducing plaque and gingivitis, and that the antimicrobial effect of S . persica is beneficial for prevention/treatment of periodontal disease . There is clearly a need for further oral health education in Saudi Arabia . Because of its close association with Islam, maximum benefits may be achieved by encouraging optimum use of the miswak . Oral hygiene may be improved by complementing traditional miswak use with modern technological developments such as toothbrushing and by tailoring oral hygiene recommendations to educational level.

Biochemistry, 2004 Jul 6, 43(26), 8459 - 69
Perturbation of the hydrophobic core of lipid bilayers by the human antimicrobial peptide LL-37; Henzler-Wildman KA et al.; LL-37 is a cationic, amphipathic alpha-helical antimicrobial peptide found in humans that kills cells by disrupting the cell membrane . To disrupt membranes, antimicrobial peptides such as LL-37 must alter the hydrophobic core of the bilayer . Differential scanning calorimetry and deuterium ((2)H) NMR experiments on acyl chain perdeuterated lipids demonstrate that LL-37 inserts into the hydrophobic region of the bilayer and alters the chain packing and cooperativity . The results show that hydrophobic interactions between LL-37 and the hydrophobic acyl chains are as important for the ability of this peptide to disrupt lipid bilayers as its electrostatic interactions with the polar headgroups . The (2)H NMR data are consistent with the previously determined surface orientation of LL-37 (Henzler Wildman, K . A., et al . (2003) Biochemistry 42, 6545) with an estimated 5-6 A depth of penetration of the hydrophobic face of the amphipathic helix into the hydrophobic interior of the bilayer . LL-37 also alters the material properties of lipid bilayers, including the area per lipid, hydrophobic thickness, and coefficient of thermal expansion in a manner that varies with lipid type and temperature . Comparison of the effect of LL-37 on 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC-d(31)) and 1,2-dimyristoyl-phosphatidylcholine (DMPC-d(54)) at different temperatures demonstrates the importance of bilayer order in determining the type and extent of disordering and disruption of the hydrophobic core by LL-37 . One possible explanation, which accounts for both the (2)H NMR data presented here and the known surface orientation of LL-37 under identical conditions, is that bilayer order influences the depth of insertion of LL-37 into the hydrophobic/hydrophilic interface of the bilayer, altering the balance of electrostatic and hydrophobic interactions between the peptide and the lipids.

Biochemistry, 2004 Jul 6, 43(26), 8391 - 409
Membrane association, electrostatic sequestration, and cytotoxicity of Gly-Leu-rich peptide orthologs with differing functions; Vanhoye D et al.; The skins of closely related frog species produce Gly-Leu-rich peptide orthologs that have very similar sequences, hydrophobicities, and amphipathicities but differ markedly in their net charge and membrane-damaging properties . Cationic Gly-Leu-rich peptides are hemolytic and very potent against microorganisms . Peptides with no net charge have only hemolytic activity . We have used ancestral protein reconstruction and peptide analogue design to examine the roles of electrostatic and hydrophobic interactions in the biological activity and mode of action of functionally divergent Gly-Leu-rich peptides . The structure and interaction of the peptides with anionic and zwitterionic model membranes were investigated by circular dichroism with 2-dimyristoyl-sn-glycero-3-phosphatidylcholine or 1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol vesicles and surface plasmon resonance with immobilized bilayers . The results, combined with antimicrobial assays, the kinetics of bacterial killing, and membrane permeabilization assays, reveal that Gly, Val, Thr, and Ile can all be accommodated in an amphipathic alpha helix when the helix is in a membrane environment . Binding to anionic and zwitterionic membranes fitted to a 2-stage interaction model (adsorption to the membrane followed by membrane insertion) . The first step is governed by hydrophobic interactions between the nonpolar surface of the peptide helix and the membranes . The strong binding of Gly-Leu-rich cationic peptides to anionic membranes is due to the second binding step and involves short-range Coulombic interactions that prolong the residence time of the membrane-inserted peptide . The data demonstrate that evolution has positively selected charge-altering nucleotide substitutions to generate an orthologous cationic variant of neutral hemolytic peptides that bind to and permeate bacterial cell membranes.

Rev Prat, 2004 Mar 31, 54(6), 591 - 7
{Nosocomial pneumonia}; Fagon JY; Nosocomial pneumonia complicates the course of a large number of hospitalized patients, associated with a higher risk of death, prolonged length of stay and over-costs . Rates of pneumonia are considerably higher in the ICU, in the post-operative period, particularly in patients treated with mechanical ventilation . Microorganisms responsible for nosocomial pneumonia are frequently multiresistant, particularly in case of late-onset pneumonia and in patients receiving prior antimicrobial therapy . Management of patients suspected of having nosocomial pneumonia aims to identify patients with true lung infection and not only colonization of the lower respiratory tract, to identify responsible pathogen(s) and to optimize the choice of antimicrobial therapy . To do that, bronchoscopic techniques with the use of bronchoalveolar lavage or protected specimen brush have the best sensitivity and specificity . Appropriate antimicrobial treatment must be initiated without delay . The potential interest of combination therapy, nebulized antibiotics needs to be clearly demonstrated by further investigations; similarly the optimal duration of treatment ensuring efficacy and avoiding the emergence and development of infections due to multiresistant pathogens remains to be more precisely evaluated.

Biometals, 2004 Jun, 17(3), 245 - 8
Potential usefulness of bovine lactoferrrin for adjunctive immunotherapy for mucosal Candida infections; Yamaguchi H et al.; Immunosuppressed children and adults have a higher prevalence of oropharyngeal candidiasis . In this patient population, anti-fungal therapy of this condition is often ineffective, and new approaches to treatment are needed . The use of bovine lactoferrin is considered a promising option in treating oropharyngeal candidiasis . Here we review the results of in vitro and in vivo studies that have examined the antimicrobial characteristics of bovine lactoferrin as an adjunctive therapy for oropharyngeal candidiasis.

Biometals, 2004 Jun, 17(3), 225 - 9
Lactoferrin and host defence: an overview of its immuno-modulating and anti-inflammatory properties; Legrand D et al.; Lactoferrin is a member of the transferrin family of iron-binding glycoproteins that is abundantly expressed and secreted from glandular epithelial cells . In secretions, such as milk and fluids of the intestinal tract, lactoferrin is an important component of the first line of host defence . During the inflammatory process, lactoferrin, a prominent component of the secondary granules of neutrophils (PMNs), is released in infected tissues and in blood and then it is rapidly cleared by the liver . In addition to the antimicrobial properties of lactoferrin, a set of studies has focused on its ability to modulate the inflammatory process and the overall immune response . Though many in vitro and in vivo studies report clear regulation of the immune response and protective effect against infection and septic shock by lactoferrin, elucidation of all the cellular and molecular mechanisms of action is far from being achieved . At the cellular level, lactoferrin modulates the migration, maturation and function of immune cells . At the molecular level and in addition to iron binding, interactions of lactoferrin with a plethora of compounds, either soluble or membrane molecules, account for its modulatory properties . This paper reviews our current understanding of the cellular and molecular mechanisms that explain the regulatory properties of lactoferrin in host defence.

Biometals, 2004 Jun, 17(3), 217 - 23
Molecular dynamics simulations of bovine lactoferricin: turning a helix into a sheet; Zhou N et al.; Bovine lactoferricin is a 25-residue peptide that is excised through pepsin cleavage in the stomach from the intact 80 kDa bovine milk protein lactoferrin . This basic peptide contains a single disulfide crosslink and is considerably more active as an antimicrobial peptide than the intact protein . It has been suggested that the dramatic difference in potency is related to a change in the secondary and tertiary structure of this peptide, moving from a mixed alpha-helical beta-strand region in the protein to an amphipathic twisted antiparallel beta-sheet in the peptide . Here we have used equilibrium and restrained molecular dynamics calculations to compare the stability of the solution structure of the isolated peptide with that excised from the intact protein . Simulations were performed for fully solvated peptides in the absence and presence of 250 mM salt . Our results show that the peptide as released from the protein is relatively unstable, particularly in the absence of salt . However, even though the simulations extended over 60 nsecs, no interconversion could be observed between the crystal and solution structures, unless a relatively small directional force was exerted on the peptide . A pathway for the structural transition from a helical to a sheet structure was identified in this fashion.

Lin Chuang Er Bi Yan Hou Ke Za Zhi, 2004 Mar, 18(3), 136 - 8
{Analysis of bacterial culture and C . pneumoniae DNA detection of chronic pharyngitis}; Xu Y et al.; OBJECTIVE: To research the pathogenic microorganism characters of chronic pharyngitis . METHOD: Samples taken from pharyngeal swab from patient with chronic pharyngitis were routinely cultured; mp-DNA were detected by polymerase chain reaction (PCR) . RESULT: Of all the cases, 5 patients were DNA(+), among which 3 patients got obvious effect after 2 weeks treatment . The bacterial abnormally was present in 15 patients (31.5%), among which 6 patients got obvious effect and 2 patients got no effect after 2 weeks treatment . CONCLUSION: The pathogenic abnormally may be present in some patients with chronic pharyngitis, most of which appeared to be an internal disorder of the proper microflores . C . pneumoniae may be an aetiological agent for chronic pharyngitis . An appropriate antimicrobial treatment should be considered in some cases.

Bioessays, 2004 Jul, 26(7), 808 - 13
Harnessing the potential of chemical defenses from antimicrobial activities; Lu C et al.; Resistance to the drugs used in the treatment of many infectious diseases is increasing, while microbial infections are being found to be responsible for more life-threatening diseases than previously thought . Despite a large investment in the invention and application of high-throughput screening techniques involving miniaturization and automation, and a diverse array of strategies for designing and constructing various chemical libraries, relatively few new drugs have resulted . Natural products, however, have been a major source of drugs for centuries . Since some of them are produced by organisms as a result of selection in favour of improved defense against competing deleterious microorganisms, in principle they would be less likely to incur resistance . Furthermore, the production of those defensive secondary metabolites is inducible because their original function is a response to environmental challenges . Moreover, symbioses, co-habitation associations between two or more different species of organisms, are universal in nature, and the production of secondary metabolites by symbiotic microbes may be an important adaptation allowing microbes to affect their hosts . Therefore, co-culture strategies, using combinations of plant cell-pathogenic microbes, plant cell-endophytes (or symbionts), and symbiont-pathogenic microbes, based on the principles of chemical defense and the known mechanisms of organism interactions, may be an efficient general approach in the search for new anti-microbial drugs .

Clin Oral Investig, 2004 Dec, 8(4), 219 - 25 Epub 2004 Dec.
Intraoral dissemination of treponemes after periodontal therapy; Ehmke B et al.; Oral treponemes are related to chronic periodontitis, but the effect of periodontal therapy on the majority of treponemal species is unknown . The aim of this prospective study was to evaluate the dynamics in prevalence profiles of treponemes in different habitats of the oral cavity . Thirty-five patients with chronic periodontitis were randomly assigned to mechanical debridement alone (control group) or systemic amoxicillin/metronidazole plus chlorhexidine (test group) . Subgingival and mucous membrane plaque samples were taken at baseline, after 10 days, and during supportive periodontal therapy at 3, 6, 9, 12, 18, and 24 months . T . denticola, T . lecithinolyticum, T . maltophilum, T . socranskii, T . vincentii, and treponemal phylotypes I-VII were detected using polymerase chain reaction (PCR) and dot blot analysis . For the majority of the assessed treponemes, a significant intragroup increase in prevalence in the different habitats ( P<0.05) occurred over the study course but, compared to debridement alone, adjunctive antimicrobial therapy resulted in a nonsignificant trend toward lower prevalence in the subgingival habitat . In no case were treponemes eradicated from the oral cavity . After both therapies, possibly new infection with and/or dissemination of Treponema ssp . occurred, which led to treponemes recovering in different habitats and to increased intraoral prevalence . The prescribed adjunctive antimicrobial therapy may limit this increase in the subgingival region.

Cornea, 2004 Jul, 23(5), 516 - 21
Fungal keratitis caused by Paecilomyces lilacinus associated with a retained intracorneal hair; Anderson KL et al.; OBJECTIVE: To report a case of fungal keratitis caused by Paecilomyces lilacinus (P . lilacinus) associated with a retained intracorneal hair . METHODS: A 61-year-old man developed pain, decreased vision, hyperemia, and corneal infiltrates in his right eye without any predisposing factor . An intracorneal hair had migrated superiorly in the corneal stroma, giving rise to 3 separate stromal infiltrates . The patient demonstrated a waxing and waning course over several months despite antimicrobial and steroid therapy . RESULTS: Histopathologic examination of a corneal biopsy specimen disclosed the presence of fungal elements, and intensive antifungal therapy was initiated . Verticillium sp . was initially identified as the causative organism, but after failure to improve on topical natamycin, subsequent investigations demonstrated the pathogen to be P . lilacinus that was resistant to routine antifungal agents . The patient was then initiated on systemic voriconazole and terbinafine . He responded well to treatment and ultimately recovered a best-corrected visual acuity of 6/15 in the affected eye . CONCLUSION: This is the first case of P . lilacinus keratitis associated with a retained intracorneal hair . Hair in the cornea could be a predisposing factor for this infection . Early corneal biopsy should be considered to properly diagnose and manage atypical keratitis and to prevent further complications.

J Clin Gastroenterol, 2004 Jul, 38(6), 503 - 6
Esomeprazole versus omeprazole for the eradication of Helicobacter pylori infection: results of a randomized controlled study; Anagnostopoulos GK et al.; BACKGROUND: Esomeprazole has higher oral bioavailability and increased antimicrobial activity against Helicobacter pylori than omeprazole . GOALS: To compare 7 days esomeprazole with 7 days of omeprazole based triple therapies for the eradication of H . pylori, and to assess whether the administration of higher dose of esomeprazole leads to improved eradication rates . STUDY: One hundred and fifty-six dyspeptic patients with H . pylori received either: (1) 1-week treatment including esomeprazole 40 mg once daily, amoxicillin 1 g, and clarithromycin 500 mg, both twice daily (EAC1 group, n = 52); (2) 1-week treatment of omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, all administered twice daily (OAC group, n = 52); or (3) 1-week treatment with esomeprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily (EAC2 group, n = 52) . RESULTS: H . pylori was eradicated in 37 of 52 patients in the OAC group (Intension to treat {ITT} 71%), and in 42 patients in the EAC1 group (ITT 81%) . High eradication rate was achieved by the EAC2 regimen (ITT; 96%), but more patients reported unwanted effects . CONCLUSION: Seven days of esomeprazole based triple therapy is a satisfactory eradication regimen for H . pylori infection . Higher doses of esomeprazole have excellent eradication rates, but they may lead to increased side effects.

Lancet Infect Dis, 2004 Jul, 4(7), 445 - 55
Global strategies to prevent bacterial pneumonia in adults with HIV disease; Feikin DR et al.; We examined the peer-reviewed literature on the burden of bacterial pneumonia and the effectiveness of interventions for its prevention among HIV-infected adults in developed and developing countries . Bacterial pneumonia rates were up to 25-fold higher among HIV-infected adults than in the general community, with rates increasing as CD4+ T-cell count decreases . In developed countries, cohort studies showed that highly active antiretroviral therapy (HAART) had the most consistent effect on reducing pneumonia . In a prospective cohort and case-control studies from these regions, pneumococcal polysaccharide vaccine reduced pneumococcal disease in certain subgroups, particularly those with higher CD4+ T cells/microL . In patients with fewer than 200 CD4+ T cells/microL, antimicrobial prophylaxis was usually effective in reducing pneumonia . In sub-Saharan Africa, randomised controlled trials concluded that co-trimoxazole prophylaxis decreased rates of bacterial pneumonia, but pneumococcal polysaccharide vaccine prevented neither pneumonia nor invasive pneumococcal disease . Although not yet fully evaluated in Africa, based on experience in industrialised nations, use of HAART in Africa may have substantial potential to prevent bacterial pneumonia.

Ceska Slov Farm, 2004 May, 53(3), 107 - 16
{Antimicrobial agents in eyedrops}; Sklubalova Z; Microbial contamination of ophthalmic drops means a risk of serious injury to the eye . Ophthalmic drops must therefore comply with sterility requirements . Protection of multiple-dose drops against secondary contamination is ensured by an addition of an antimicrobial agent . Selection of a suitable antimicrobial agent is conditioned by many factors, such as the spectrum of effect, properties of the preparation, compatibility with the components of the preparation and the container, and the technology of manufacture . Although the added antimicrobial substance ensures the safety of the preparation, on the other hand it can produce a number of negative effects in the eye tissue . The present paper summarizes pharmacopoeial requirements for microbial quality of ophthalmic drops, outlining the properties and efficacy of antimicrobial substances commonly used in ophthalmic drops (benzalkonium chloride BAC, cetrimide CTM, phenyl mercuric salts PHg, thiomersal TM, chlorobutanol ChB, benzyl alcohol BA, phenyl ethyl alcohol PEA, chlorohexidin ChX, parabens PB), their typical concentrations and combinations, including the parameters of formulation and the interactions which affect their activity . It deals with the toxicity of these antimicrobial substances, side effects on the eye tissue, and alternatives to the use of antimicrobial agents.

Jpn J Infect Dis, 2004 Jun, 57(3), 103 - 6
Factors improving the propagation of Simkania negevensis strain Z in cell culture; Yamaguchi T et al.; The purpose of the present study was to develop an optimal method for culturing Simkania negevensis . Centrifugation was effective for the propagation of S . negevensis, but sonication was not effective . The addition of cycloheximide to the culture medium significantly decreased the number of inclusions . Pretreatment of host monolayers with diethylaminoethyl-dextran or polyethylene glycol was detrimental . The most optimal conditions were centrifugation of the inocula onto untreated Vero cells, and culture in RPMI 1640 medium containing 10% fetal calf serum without cycloheximide or antimicrobial agents.

Nucleic Acids Res, 2004 Jul 1, 32(Web Server issue), W10 - 5
The web server of IBM's Bioinformatics and Pattern Discovery group: 2004 update; Huynh T et al.; In this report, we provide an update on the services and content which are available on the web server of IBM's Bioinformatics and Pattern Discovery group . The server, which is operational around the clock, provides access to a large number of methods that have been developed and published by the group's members . There is an increasing number of problems that these tools can help tackle; these problems range from the discovery of patterns in streams of events and the computation of multiple sequence alignments, to the discovery of genes in nucleic acid sequences, the identification--directly from sequence--of structural deviations from alpha-helicity and the annotation of amino acid sequences for antimicrobial activity . Additionally, annotations for more than 130 archaeal, bacterial, eukaryotic and viral genomes are now available on-line and can be searched interactively . The tools and code bundles continue to be accessible from whereas the genomics annotations are available at http://cbcsrv.watson.ibm.com/Annotations/.

J Antimicrob Chemother, 2004 Aug, 54(2), 481 - 8 Epub 2004 Jun 23.
Influence of penicillin resistance on outcome in adult patients with invasive pneumococcal pneumonia: is penicillin useful against intermediately resistant strains?
Falco V, Almirante B, Jordano Q, Calonge L, del Valle O, Pigrau C, Planes AM, Gavalda J, Pahissa A.
OBJECTIVES: To compare outcome between patients with pneumonia due to penicillin-susceptible S . pneumoniae and patients with pneumonia due to penicillin intermediately resistant strains and to study the outcome of patients with pneumococcal pneumonia caused by strains with MICs of 0.12-1 mg/L treated empirically during the first 48 h with beta-lactam antibiotics . MATERIALS AND METHODS: We studied 247 adult patients with invasive pneumococcal pneumonia occurring from 1997 to 2001 . The following data were recorded from each patient: socio-demographic characteristics, underlying diseases, clinical presentation, initial severity of pneumonia, initial and subsequent antimicrobial therapy, in-hospital complications, hospital mortality and length of hospital stay . Multivariate analysis was done to identify variables associated with the development of pneumonia caused by a non-susceptible strain . RESULTS: The overall presence of penicillin non-susceptibility was 26.7%; no strain had an MIC >2 mg/L . Overall mortality was 23.5% in patients with pneumonia caused by intermediately resistant pneumococci and 12.7% in those with pneumonia caused by susceptible strains (P=0.075) . Mortality during the first 7 days of admission, considered to be pneumonia-related deaths (13.7% versus 9.9%; P=0.448) was similar in both groups . The multivariate analysis showed that serotype 14 (OR, 140.18; 95% CI, 16.95-1159.20), serotype 19 (OR, 7.53; 95% CI, 1.98-28.7), haematological malignancy or splenectomy (OR, 4.46; 95% CI, 1.5-13.23) and HIV infection (OR, 4.54; 95% CI, 1.54-13.44) were the only independent factors associated with pneumonia caused by penicillin intermediately resistant pneumococci . In patients with strains having MICs of 0.1-1 mg/L, overall mortality was similar in the group of penicillin-treated patients (22.2%) to those treated with broad-spectrum beta-lactams (23.5%) . CONCLUSIONS: There is a non-significant trend to higher mortality in patients with pneumococcal pneumonia caused by intermediately resistant strains; however, they do not have a poorer outcome when they are treated with amoxicillin.

J Antimicrob Chemother, 2004 Aug, 54(2), 508 - 14 Epub 2004 Jun 23.
Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients; Badia JR et al.; BACKGROUND: Delivery of antibiotics to the lower respiratory tract could potentially achieve antimicrobial bronchial drug concentrations without toxicity . AIM: To assess bronchial and serum concentrations of imipenem or tobramycin obtained by nebulization or instillation in critically ill mechanically ventilated patients . METHODS: Prospective randomized open trial . Eighteen patients ventilated for more than 48 h were included . Two doses of imipenem/cilastatin (1000/500 mg) separated by 8 h, or two doses of tobramycin 200 mg separated by 12 h were randomly nebulized or instilled into the tracheal tube . Five bronchoaspirates (two bronchoscopic, three blind) and five blood samples were collected on a timed schedule after the second dose . Respiratory and serum samples were analysed by HPLC, and a subset of blood samples was also evaluated by enzyme-immunoassay . RESULTS: When instilled, imipenem/cilastatin obtained higher concentrations in respiratory secretions than when nebulized (P=0.022, 1 h after the last dose; P=0.029, 2 h after the last dose) . Tobramycin showed equally high concentrations when nebulized or instilled . Instillation of tobramycin may result in significant accumulation in patients with renal failure . CONCLUSIONS: High bronchial concentrations of imipenem could only be achieved by instillation, whereas tobramycin seems suitable for both modes of administration . Instillation of these antibiotics is a safe procedure that achieves high drug concentrations in respiratory secretions.

Antimicrob Agents Chemother, 2004 Jul, 48(7), 2778 - 81
Enhancement of the enterocin CRL35 activity by a synthetic peptide derived from the NH2-terminal sequence; Saavedra L et al.; The enterocin CRL35 biosynthetic gene cluster was cloned and sequenced . The sequence was revealed to be highly identical to that of the mundticin KS gene cluster (S . Kawamoto, J . Shima, R . Sato, T . Eguchi, S . Ohmomo, J . Shibato, N . Horikoshi, K . Takeshita, and T . Sameshima, Appl . Environ . Microbiol . 68:3830-3840, 2002) . Short synthetic peptides were designed based on the bacteriocin sequence and were evaluated in antimicrobial competitive assays . The peptide KYYGNGVSCNKKGCS produced an enhancement of enterocin CRL35 antimicrobial activity in a buffer system.

Eur J Immunol, 2004 Jul, 34(7), 1777 - 82
Mini-review: the role of peptidoglycan recognition in innate immunity; Girardin SE et al.; The importance of peptidoglycan detection in the host innate immune response has long been underestimated . However, the recent identification of proteins involved in the sensing of peptidoglycan in both mammals and Drosophila has revealed that the detection of this microbial motif is key to the defense response . In Drosophila, the peptidoglycan-recognition proteins (PGRP) are the initial sensors of infecting bacteria that then trigger a cascade ultimately leading to the expression of antimicrobial peptides . In mammals, PGRP also exist and although they bind peptidoglycan, the role of these proteins in innate immune responses remains to be clearly defined . In contrast, the Nod proteins (Nod1 and Nod2), which are also involved in peptidoglycan sensing, appear to play a key role in innate immunity against bacteria by triggering host defense responses through the activation of the transcription factor, NF-kappaB . Interestingly, mutations in Nod2 are related to increased susceptibility to Crohn's disease, thereby implicating defective bacterial sensing in the development at this chronic disease . In this review, we will focus on the recent findings concerning mammalian and Drosophila proteins involved in peptidoglycan recognition and the putative role of these proteins in the innate immune defense response.

Fish Shellfish Immunol, 2004 Aug, 17(2), 171 - 85
Recombinant transferrin induces nitric oxide response in goldfish and murine macrophages; Stafford JL et al.; We have previously demonstrated that the serum protein transferrin plays a key role in the activation of primary goldfish macrophages . The ability of this protein to activate goldfish macrophages was also shown to be dependent on enzymatic cleavage of the native (i.e . full-length) protein into immunostimulatory fragments . In this study, we report that immunostimulatory fragments of recombinant goldfish transferrin (rGTf), induced a potent nitric oxide (NO) response in goldfish as well as in murine macrophages . Specifically, recombinant goldfish transferrin N- and C-lobe fragments expressed in Escherichia coli induced the NO response in goldfish and murine macrophages . As little as 75-150 ng of the recombinant proteins (N- or C-lobe) had biological activity, even in the presence of 10 microg/ml of the LPS inhibitor polymixin B sulphate (PMB) . These findings indicate that transferrin is a key conserved component required for induction of macrophage antimicrobial responses of fish and provide evidence that a similar induction pathway exists in mammals, which has not been reported previously.

Drugs, 2004, 64(13), 1465 - 78
Adapalene: a review of its use in the treatment of acne vulgaris; Waugh J et al.; Adapalene (Differin) is a retinoid agent indicated for the topical treatment of acne vulgaris . In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel . It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment . Adapalene has a rapid onset of action and a particularly favourable tolerability profile compared with other retinoids . These attributes can potentially promote patient compliance, an important factor in treatment success . Adapalene is, therefore, assured of a role in the first-line treatment of acne vulgaris.

Kansenshogaku Zasshi, 2004 May, 78(5), 420 - 7
{Susceptibility testing and molecular epidemiology of clinical strains of Bordetella pertussis isolated in Japan from 2001 to 2002}; Ohtsuka M et al.; We determined antimicrobial susceptibilities and analyzed molecular epidemiology of 26 strains of Bordetella pertussis clinically isolated and then performed pulsed-field gel electrophoresis (PFGE) in Japan (Japanese Pertussis Surveillance Group Participants), from 2001 to 2002 . The MICs of erythromycin, clindamycin, tetracyclines, fluoroquinorones, trimethoprim-sulfamethoxazole and rifampicin of all isolates against these showed 1 microgram/ml or less . Sparfloxacin is the most potent agent, of which the MICs showed 0.008-0.016 microgram/ml . Results of DNA fingerprinting by pulsed-field gel electrophoresis (PFGE) differentiated three types (Type I; 11 strains (42%), type II; 14 strains (54%) and type III; 1 strains (4%)) . However, no relation between regions and identical PFGE patterns was found in this study . Further, surveillance of the antimicrobial susceptibilities and molecular epidemiology of B . pertussis will be required.

J Cell Biochem, 2004 Jul 1, 92(4), 849 - 63
Hemolymph-dependent and -independent responses in Drosophila immune tissue; Bettencourt R et al.; Insects possess an antimicrobial defense response that is similar to the mammalian innate immune response . The innate immune system is designed to recognize conserved components of microorganisms called pathogen-associated molecular patterns (PAMPs) . How host receptors detect PAMPs and transmit the signals to mount the immune response is being elucidated . Using GFP-Dorsal, -Dif, and -Relish reporter proteins in ex vivo assays, we demonstrate that Drosophila fat bodies, a major immune tissue, have both hemolymph-dependent and -independent responses . Microbial preparations such as lipoteichoic acid (LTA) and peptidoglycan (PGN) can stimulate some responses from dissected and rinsed larval fat bodies . Therefore, at least some aspects of recognition can occur on fat body cell surfaces, bypassing the requirement of hemolymph . Our results also show that supernatants from bacterial cultures can stimulate the nuclear translocation of Dorsal in dissected fat bodies, but this stimulation is strictly hemolymph-dependent . Various biochemical assays suggest that the factors from bacterial supernatants that stimulate the hemolymph-dependent nuclear translocation are likely made up of proteins . We further show that Dorsal mutant larvae have much lower phenoloxidase activity, consistent with a more important role of Dorsal in innate immunity than previously shown .

J Immunol, 2004 Jul 1, 173(1), 428 - 36
Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor; Sun R et al.; The antimicrobial and proinflammatory neutrophil granule protein cathepsin G (CaG) has been reported as a chemoattractant for human phagocytic leukocytes by using a putative G protein coupled receptor . In an effort to identify potential CaG receptor(s), we found that CaG-induced phagocyte migration was specifically attenuated by the bacterial chemotactic peptide fMLP, suggesting these two chemoattractants might share a receptor . In fact, CaG chemoattracts rat basophilic leukemia cells (RBL cells) expressing the high affinity human fMLP receptor FPR, but not parental RBL cells or cells transfected with other chemoattractant receptors . In addition, a specific FPR Ab and a defined FPR antagonist, cyclosporin H, abolished the chemotactic response of phagocytes and FPR-transfected cells to CaG . Furthermore, CaG down-regulated the cell surface expression of FPR in association with receptor internalization . Unlike fMLP, CaG did not induce potent Ca(2+) flux and was a relatively weaker activator of MAPKs through FPR . Yet CaG activated an atypical protein kinase C isozyme, protein kinase Czeta, which was essential for FPR to mediate the chemotactic activity of CaG . Thus, our studies identify CaG as a novel, host-derived chemotactic agonist for FPR and expand the functional scope of this receptor in inflammatory and immune responses.

Bioorg Chem, 2004 Aug, 32(4), 193 - 210
Synthesis and antimicrobial activity of meso-substituted polymethine cyanine dyes; Abd El-Aal RM et al.; The condensation reaction of equivalent amounts of 2-cyanomethyl benzooxazole or its derivatives with variously substituted aromatic aldehydes gave 2-cyano-styryl benzooxazole or its derivatives . The subsequent reaction of the 2-cyano-styryl benzooxazoles with 2(4)-methyl substituted heterocyclic quaternary salts afforded meso-substituted styryl-2(4)-polymethine cyanines . The condensation reaction of 2-cyanomethyl benzooxazole or its derivatives with alpha-nitroso-beta-naphthol followed by reaction with 2(4)-methyl substituted heterocyclic quaternary salts gave meso-substituted aza-2(4)-polymethine cyanines . The reaction of 2-cyanomethyl benzooxazole or its derivatives with N-methyl heterocyclic quaternary salts followed by the reaction with 2-methylquinolinium methiodide afforded the corresponding meso-substituted trimethine cyanine dyes . Elemental analyses, visible absorption, IR, (1)H NMR spectroscopy, and mass spectra established the structures of these compounds . The relationship between the structure and properties of these dyes has been studied and the solvatochromic behavior of some selected cyanine dyes in organic solvents is discussed . Finally, the antimicrobial activity of selected novel dyes was investigated in vitro using a wide spectrum of microbial strains.

Bioorg Med Chem, 2004 Jul 15, 12(14), 3825 - 30
New phenolic inhibitors of yeast homoserine dehydrogenase; Ejim L et al.; A relatively unexploited potential target for antimicrobial agents is the biosynthesis of essential amino acids . Homoserine dehydrogenase, which reduces aspartate semi-aldehyde to homoserine in a NAD(P)H-dependent reaction, is one such target that is required for the biosynthesis of Met, Thr, and Ile from Asp . We report a small molecule screen of yeast homoserine dehydrogenase that has identified a new class of phenolic inhibitors of this class of enzyme . X-ray crystal structural analysis of one of the inhibitors in complex with homoserine dehydrogenase reveals that these molecules bind in the amino acid binding region of the active site and that the phenolic hydroxyl group interacts specifically with the backbone amide of Gly175 . These results provide the first nonamino acid inhibitors of this class of enzyme and have the potential to be exploited as leads in antifungal compound design.

Bioorg Med Chem, 2004 Jul 15, 12(14), 3807 - 13
Synthesis and antimicrobial activity of erythromycin-A oxime analogs; Pandey D et al.; A series of erythromycin-A oxime ether as well as esters have been synthesized . Ether derivatives were synthesized through the epoxy ether intermediate of erythromycin-9-oxime, followed by opening of the epoxy linkage through various amines, whereas esters have been prepared through DCC mediated protocol . These derivatives have been evaluated for antibacterial activity and found to be as active as erythromycin-A.

Acta Odontol Latinoam, 2002, 15(1-2), 15 - 9
Changes of pH produced by immersion of endodontic sealers; Molgatini SL et al.; When evaluating the antimicrobial effect of endodontic sealers it is important to study the variation of pH, since this is one of the properties that may inhibit the microbial growth and influence biocompatibility . The aim of this study was to evaluate the capacity of several endodontic sealers without calcium hydroxide to modify the pH of the solution in which they were immersed . The sealers used were: Endomethasone C-Septodont (EC), Bio Seal-Ogna (BS), Diaket-Espe (D), Procosol-StarDental (P), AH26-Dentsply (AH), Ketac Endo-Espe (KE), AHPlus-Dentsply (AHP), Endion-Voco (E), Endomethasone-Septodont (EM), EZ Fill-Essential Dental Systems (EZ) . Samples of each material were placed in tubes with phosphate saline solution (PBS) . The pH was determined at 2, 5, 12, 20, 30, 60, and 90 days . A tube with solution alone was taken as control . Statistical analysis of the results was performed by ANOVA . Material, sample, time and material-time interaction elicited statistically significant differences (p < 0.05) . The variation of pH produced by immersion of endodontic sealers depends on the composition of the material.

Res Microbiol, 2004 Jun, 155(5), 360 - 9
Adaptation to the deleterious effects of antimicrobial drug resistance mutations by compensatory evolution; Maisnier-Patin S et al.; Compensatory mutations, due to their ability to mask the deleterious effects of another mutation, are important for the adaptation and evolution of most organisms . Resistance to antibiotics, antivirals, antifungals, herbicides and insecticides is usually associated with a fitness cost . As a result of compensatory evolution, the initial fitness costs conferred by resistance mutations (or other deleterious mutations) can often be rapidly and efficiently reduced . Such compensatory evolution is potentially of importance for (i) the long-term persistence of drug resistance, (ii) reducing the rate of fitness loss associated with the accumulation of deleterious mutations in small asexual populations, and (iii) the evolution of complexity of cellular processes.

Clin Immunol, 2004 Jul, 112(1), 8 - 23
The immunoregulatory role of CD1d-restricted natural killer T cells in disease; van der Vliet HJ et al.; Natural killer T (NKT) cells constitute a T cell subpopulation that shares several characteristics with NK cells . NKT cells are characterized by a narrow T cell antigen receptor (TCR) repertoire, recognize glycolipid antigen in the context of the monomorphic CD1d antigen-presenting molecule, and have the unique capacity to rapidly produce large amounts of both T helper (Th) 1 and Th2 cytokines . Important roles of NKT cells have now been demonstrated in the regulation of autoimmune, allergic, antimicrobial, and antitumor immune responses . Here, we review the immunoregulatory role of NKT cells in disease and discuss NKT cell based immunotherapeutic strategies.

Life Sci, 2004 Jul 16, 75(9), 1123 - 34
High concentrations of alpha-defensins in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome; Ashitani J et al.; alpha-Defensins, antimicrobial peptides localized in neutrophils, participate in tissue damage through their cytotoxic effects in neutrophil-mediated pulmonary diseases . Neutrophils play an important role in the pathogenesis of acute respiratory distress syndrome (ARDS) . We measured alpha-defensins levels in plasma and bronchoalveolar lavage fluid (BALF) of ARDS patients to assess the kinetics of alpha-defensins in ARDS . Plasma alpha-defensins levels were higher in ARDS patients than in control subjects, and BALF levels were also higher in ARDS patients than in control subjects . In ARDS, BALF alpha-defensins levels correlated with those of interleukin (IL)-8, and plasma alpha-defensins levels also correlated with Lung Injury Score . Peripheral neutrophil alpha-defensins contents were higher in ARDS than the control . IL-8 dose-dependently stimulated alpha-defensins release from cultured neutrophils and these levels were higher in ARDS than the control . Reverse-phase high performance liquid chromatography showed high plasma levels of pro-defensins, precursors of alpha-defensins from the bone marrow in ARDS, although alpha-defensins in peripheral and BALF neutrophils were mature type . In conclusion, high plasma alpha-defensins in ARDS patients result from the release of pro-defensins from bone marrow, rather than mature alpha-defensins from neutrophils that accumulate in the alveolar space . The alpha-defensins contents of peripheral neutrophils in ARDS are higher and easier to release than control .

Emerg Infect Dis, 2004 Jun, 10(6), 1088 - 94
Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States; Duck WM et al.; Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer . H . pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure . The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S . network that tracks national incidence rates of H . pylori antimicrobial resistance . Of 347 clinical H . pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents . Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin . On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H . pylori strain . Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice.

Emerg Infect Dis, 2004 Jun, 10(6), 1082 - 7
Limited spread of penicillin-nonsusceptible pneumococci, Skåne County, Sweden; Melander E et al.; In response to increasing frequencies of penicillin-nonsusceptible pneumococci (PNSP), for which the MIC of penicillin was >0.12 mg/L, in Skane County, southern Sweden, national recommendations were initiated in 1995 to limit the spread of pneumococci with high MICs (> or =0.5 mg/L) of penicillin (PRP), especially among children of preschool age . Traditional communicable disease control measures were combined with actions against inappropriate antimicrobial drug use . During the first 6 years that these recommendations were applied in Skane County, the average frequency of penicillin-resistant pneumococci has been stable at =2.6%, as has the average PNSP frequency (7.4%) . However, PNSP have been unevenly distributed in the county, with the highest frequencies in the southwest . Simultaneously, the rate of antimicrobial drug use for children <6 years of age was reduced by 20% . Thus the spread of PNSP between and within the municipalities in the county has been limited.

J Periodontal Res, 2004 Aug, 39(4), 221 - 7
Expression of human beta-defensins-1 and -2 peptides in unresolved chronic periodontitis; Lu Q et al.; BACKGROUND: Human beta-defensins (hBDs) are antimicrobial peptides which contribute to host innate immunity by disrupting the membrane integrity of a broad spectrum of microorganisms . OBJECTIVES: This study aimed to determine the expression profiles of hBD-1 and -2 peptides in gingiva and to assess the possible relations of these antimicrobial peptides with periodontal health and disease . METHODS: Seven periodontally healthy subjects and 22 patients with unresolved chronic periodontitis were recruited and the gingival biopsies collected consisted of healthy tissues from the healthy subjects (HT-C); periodontal pocket tissues (PoT) and inflamed connective tissues (ICT) from the base of pocket, i.e . granulation tissues, as well as clinically healthy tissues (HT-P) from the adjacent clinically healthy sites from the patients . The expression of hBD-1 and -2 peptides was detected by immunohistochemistry and quantitatively analyzed with a computerized image processing system . RESULTS: Both hBD-1 and -2 peptides were detected in all periodontally healthy subjects, while hBD-1 was detected in all patients and hBD-2 was found in most of the patients . Their expression was mainly confined to the granular and spinous layers of gingival epithelium, in which hBD-1 was detected in both intercellular spaces and cytoplasm, whereas hBD-2 was mainly observed in the cytoplasm . HT-C expressed significantly higher levels of hBD-2 than HT-P (p < 0.05) . Within the patients, both defensins were up-regulated significantly in PoT as compared with the adjacent HT-P (p < 0.05) . CONCLUSIONS: The present study showed that hBD-1 and -2 were frequently expressed in the granular and spinous layers of gingival epithelia and their expression may be associated with periodontal health and disease . Copyright Blackwell Munksgaard, 2004

Adv Exp Med Biol, 2003, 527, 629 - 36
Tryptophan-derived sulfur-containing phytoalexins--a general overview; Ruszkowska J et al.; Phytoalexins are low molecular weight antimicrobial compounds that are synthesized and accumulated in plants after their exposure to pathogenic microorganisms (bacteria, fungi, viruses and protozoans) . They are extensively studied now as promising antifungal, potentially anticancer and plant diseases controlling agents . The article pertains to a group of indole-derived phytoalexins--brassinins, containing at least one sulfur atom in the side chain or in the ring(s), isolated from the cruciferous plants . Up today more than 20 compounds, closely related biogenetically, but exhibiting diversified biological activity have been identified . The survey summerises most promising recent results pertaining practical application of brassinins and camalexins.

Poult Sci, 2004 Jun, 83(6), 990 - 6
Effects of copper source on phosphorus retention in broiler chicks and laying hens; Banks KM et al.; Copper sulfate is often added to broiler and laying hen diets at prophylactic dosages due to its antimicrobial and growth promoting effects despite reduced P digestibility, whereas P use from other Cu sources is unknown . Therefore, male broiler chicks were fed diets containing 0 or 250 ppm Cu from Cu sulfate (Cu SUL), Cu citrate (Cu CIT), Cu lysinate (Cu LYS), or CuCl from 9 to 22 d of age (8 cages/diet, 6 birds/cage) to determine the effect of each Cu source on performance characteristics, bone mineralization, and P retention . Body weight gain was not different among treatments (P > 0.05) . Supplementation with 250 ppm Cu from Cu LYS resulted in chicks having greater toe and tibia ash weights as compared with chicks fed Cu SUL (P < or = 0.05) but was not significantly different from those of birds fed Cu CL, Cu CIT, and 0 ppm Cu diets . Supplementation with Cu LYS resulted in birds with greater toe ash percentage as compared with birds fed Cu CIT, Cu SUL, and the 0 ppm Cu diets (P < or = 0.05) but was not significantly different than those of birds fed the CuCl diet . Birds fed the Cu LYS diet had greater tibia ash percentage as compared with birds fed Cu SUL and 0 ppm Cu diets (P < or = 0.05) but were not significantly different than birds fed the Cu CL or Cu CIT diet . Supplementation with 250 ppm Cu SUL or Cu CIT reduced apparent P retention by 0.029 and 0.053 percentage-units of the diet, respectively (P < or = 0.05) as compared with the 0 ppm diet; whereas the apparent P retention when 250 ppm Cu LYS or Cu CL was fed was not different from the 0 ppm Cu diet (P > 0.05) . Feeding of different Cu sources in a subsequent experiment had no influence on P retention in laying hens (P > 0.05) . In conclusion, supplementation with 250 ppm Cu from Cu CIT or Cu SUL resulted in decreased apparent P retention . Supplementation with 250 ppm Cu CL or Cu LYS, however, improved apparent P retentions as compared with Cu CIT or Cu SUL.

Eur Rev Med Pharmacol Sci, 2003 Nov-Dec, 7(6), 171 - 3
Protein profile of Helicobacter pylori strains by isoelectrofocusing in patients affected by chronic gastritis; Barbaro SP et al.; BACKGROUND: To understand if relapse, following antimicrobial treatment was due to re-infection or to recrudescence . METHODS: Fifty patients with dyspepsia were studied prospectively . They were followed up by endoscopy and biopsy of antral mucosa before and after treatment with anti-microbial therapy . Gel isoelectrofocusing was used to characterize protein profile of Hp . RESULTS: At baseline 40 patients were affected by chronic gastritis associated with Hp . At the end of treatment 75% patients given omeprazole, amoxicillin and clarithromycin were Hp infected: 43% showed the same protein profile and 57% different . CONCLUSIONS: Our data suggest that the relapse is due to recrudescence or to reinfection.

Clin Infect Dis, 2004 Jul 1, 39(1), 107 - 14 Epub 2004 Jun 14.
Antimicrobial-specific cell-mediated immune reconstitution in children with advanced human immunodeficiency virus infection receiving highly active antiretroviral therapy; Weinberg A et al.; To identify virological and immunological correlates of microbial-specific immune reconstitution in children with advanced human immunodeficiency virus (HIV) infection, Candida- and tetanus-specific lymphocyte proliferation was measured in 165 children initiating a new highly active antiretroviral therapy (HAART) regimen . During the study, the proportions of children with immunity to Candida and tetanus increased from 53% to 66% and 19% to 22%, respectively . Tetanus immunity was associated with an HIV load < or =400 RNA copies/mL and with Candida immunity . At the end of the study, 23% of the patients with baseline negative lymphocyte proliferation had tetanus immunity, and 65% had Candida immunity . Reconstitution of tetanus immunity correlated with lower end-of-study HIV loads and activated CD8+ cell percentages and higher baseline and in-study CD4+ cell percentages, but not with a gain of CD4+ cells . Reconstitution of Candida immunity showed similar trends . In conclusion, children with advanced HIV infection receiving HAART reconstituted Candida immunity more readily than they did tetanus immunity, suggesting a role for antigen reexposure . Additional factors for immune reconstitution were low HIV load, high CD4+ cell percentages, and low levels of activated CD8+ cells.

Clin Infect Dis, 2004 Jul 1, 39(1), 83 - 91 Epub 2004 Jun 14.
Aging and infectious diseases in the developing world; Gavazzi G et al.; Although demographic aging does not remain restricted to industrialized countries, the medical challenge arising from the aging population will be distinct in the developing world . This is particularly true with respect to infectious diseases, which have a distinct spectrum in the elderly population, as well as a greater overall relevance in the developing world . Tropical diseases have a specific presentation and epidemiology in elderly patients . Infectious diseases with a worldwide distribution impact elderly patients in the developing world in a specific manner, which is most obvious with respect to human immunodeficiency virus and tuberculosis but is also true with respect to "trivial" manifestations of infection, such as diarrhea and pneumonia . Malnutrition contributes in a major way to the immunodeficiency of elderly patients in the developing world . Poorly controlled use of antimicrobial drugs leads to multidrug-resistant microorganisms, which, together with the limited resources available for drug treatment, makes appropriate treatment of infections in elderly patients in developing countries very difficult . Infections in elderly patients will have an increasing impact on the public health and economy of developing countries.

Clin Infect Dis, 2004 Jul 1, 39(1), 11 - 7 Epub 2004 Jun 01.
Per capita antibiotic consumption: how does a North American jurisdiction compare with Europe?
Patrick DM, Marra F, Hutchinson J, Monnet DL, Ng H, Bowie WR.
Antibiotic consumption in populations affects the emergence of resistant organisms . We compared 1996-2000 trends in consumption in British Columbia, Canada, with those in Europe . Prescription data from the British Columbia PharmaNet database were converted into SAS files and classified using the Anatomical Therapeutic Chemical system, and weights of antibiotics were converted into defined daily doses (DDDs) using the 2001 definitions from the World Health Organization Collaborating Center for Drug Statistics Methodology . During 1996-2000, consumption in British Columbia decreased from 19.5 to 17.9 DDDs/1000 inhabitant-days . Although antibiotic consumption in British Columbia was less than the European median in 2000, it exceeded that in northern European countries with established antibiotic surveillance and control programs . The consumption rates for fluoroquinolones, newer macrolides, and cephalosporins in British Columbia exceeded those in Denmark (1.44 vs . 0.15, 1.59 vs . 0.92, and 1.86 vs . 0.02 DDDs/1000 inhabitant-days, respectively) . The observed increase in and pattern of consumption associated with newer antimicrobials may increase the risk for emergence of antimicrobial-resistant organisms in British Columbia.

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 2004 Apr, 47(4), 363 - 8
{Antibiotic-resistant nosocomial pathogens . Part II: scrutiny of regionally occurring bacteria according to section sign 23 section 1 of the Protection Against Infection Act}; Hock MR; Scrutiny of regionally occurring bacteria with unusual forms of resistance to antimicrobials according to section sign 23 section 1 of the Protection Against Infection Act is useful for individual hospitals in assessing their own resistance situation . This study summarizes frequencies of antimicrobial resistances in 19 hospitals in the Berlin region in 2001 and 2002 . MRSA so far is the only bacterium of epidemiological significance, other resistance phenomena bearing relevance for individual hospitals only . The average incidences of MRSA in hospitals and their "risk areas" in comparison to a particular hospital can serve as an indicator for unusually high resistance rates or nosocomial outbreaks . Using one hospital outbreak as an example, possibilities are presented for recording incidences and implementing measures to successfully reduce the MRSA incidence.

Scand J Urol Nephrol, 2004, 38(2), 168 - 73
Nocardial infection in immunosuppressed kidney transplant recipients; Queipo-Zaragoza JA et al.; OBJECTIVE: Nocardiosis is a very rare, opportunistic infection caused by microorganisms of the genus Nocardia, and is associated with significant morbidity and mortality in kidney transplant patients receiving immunosuppressive therapy . MATERIAL AND METHODS: Since 1980, our Renal Transplant Unit has carried out 1239 kidney transplants, and five cases of Nocardia infection have occurred during this time . In this retrospective study, special consideration is given to clinical manifestations, treatment response (efficacy and side-effects) and the evolution of both the patient and the graft . Microbiological factors studied included biochemical profiles and antimicrobial sensitivity . RESULTS: Nocardiosis was observed in five men with a mean age of 49.2 years who had received immunosuppressive therapy (generally cyclosporin/azathioprine and prednisone) for a mean of 47.8 months (range 1-148 months) . Four of the patients had good previous renal function . The clinical presentation of nocardiosis was as follows: pleuropulmonary pattern of infection, n = 3; subcutaneous abscess, n = 1; and fulminant multi-organ disseminated nocardiosis, n = 1 . In all cases, direct observation using modified Ziehl-Neelsen staining proved positive, and in vitro culture revealed good sensitivity to trimethoprim-sulfamethoxazole and variable sensitivity to the other groups of antibiotics . Nocardia brasiliensis was isolated in two cases, and Nocardia asteroides in three . Two patients died, one due to multiple organ involvement and the other due to acute respiratory failure associated with severe hepatopathy caused by hepatitis C virus . The remaining cases improved . CONCLUSION: A low incidence of nocardiosis following kidney transplantation was observed . Fatal cases occurred in patients with bacteremia and serious comorbid medical conditions, in whom early diagnosis and specific treatment was required.

J Drug Target, 2003 Aug, 11(7), 415 - 23; discussion 423-4
Receptor mediated targeting of lectin conjugated gliadin nanoparticles in the treatment of Helicobacter pylori; Umamaheshwari RB et al.; The present work describes the potential for using lectin-conjugated gliadin nanoparticles as a means of locating and anchoring a drug delivery system on the carbohydrate receptors of Helicobacter pylori (H . pylori) . Gliadin nanoparticles (GNP) bearing acetohydroxamic acid (AHA) were prepared by a desolvation method . Ulex Europaeus Agglutinin I (UEA I) and Conconavalin A (Con A) lectins were bound to GNP formulations by the two-stage carbodiimide coupling technique . Lectin-agglutination assay was performed to evaluate the binding efficacy of lectin formulations to carbohydrate receptors of H . pylori strains . Strong agglutination patterns were observed with mannose-specific Con A-GNP and alpha(L)-fucose specific UEA-GNP formulations . In situ adherence assay was performed to examine the efficacy of lectin formulations to inhibit the binding of H . pylori strains with human stomach cells . Lectin formulations completely inhibited the H . pylori binding . In addition, the antimicrobial activity of the formulations was evaluated by percent growth inhibition studies (%GI) by using isolated H . pylori strain . The inhibitory efficacy of UEA-GNP and Con A-GNP was approximately two-fold higher compared to GNP . These lectin-conjugated gliadin nanoparticles are found to be potential candidate for targeted drug delivery and are anticipated to be useful in the treatment of H . pylori.

Pathology, 2004 Apr, 36(2), 170 - 3
Catheter-drawn blood cultures: is withdrawing the heparin lock beneficial?
Everts R, Harding H.
AIMS: To assess the potential benefit of withdrawing or flushing away the heparin lock before collecting blood for culture from a central venous catheter . METHODS: We compared the contamination rates of 152 pairs of blood samples aspirated from central venous catheters in afebrile renal dialysis or cancer patients . We also assessed the antimicrobial effect of 2000 U of heparin in Bactec Plus Aerobic/F culture bottles inoculated with a volunteer's blood plus one of six common bloodstream pathogens . RESULTS: There was no significant difference in contamination rates between first-drawn (26 of 152, 17.1%) and second-drawn (24 of 152, 15.8%) samples . There was no significance difference in yield (58 of 60 {97%} versus 52 of 53 {98%}) or time to flagging positive (16.6 versus 16.7 h) between the bottles with and without heparin . CONCLUSIONS: Our results do not support the practice of withdrawing or flushing away the heparin lock before collecting blood for culture from a central venous catheter.

Peptides, 2004 Jun, 25(6), 1035 - 54
Host-defence peptides of Australian anurans: structure, mechanism of action and evolutionary significance; Apponyi MA et al.; Host-defence peptides secreted from the skin glands of Australian frogs and toads, are, with a few notable exceptions, different from those produced by anurans elsewhere . This review summarizes the current knowledge of the following classes of peptide isolated and characterized from Australian anurans: neuropeptides (including smooth muscle active peptides, and peptides that inhibit the production of nitric oxide from neuronal nitric oxide synthase), antimicrobial and anticancer active peptides, antifungal peptides and antimalarial peptides . Other topics covered include sex pheromones of anurans, and the application of peptide profiling to (i) . recognize particular populations of anurans of the same species and to differentiate between species, and (ii) . investigate evolutionary aspects of peptide formation.

Peptides, 2004 Jun, 25(6), 919 - 28
Jelleines: a family of antimicrobial peptides from the Royal Jelly of honeybees (Apis mellifera); Fontana R et al.; Four antimicrobial peptides were purified from Royal Jelly of honeybees, by using reverse phase-HPLC and sequenced by using Q-Tof-MS/MS: PFKLSLHL-NH(2) (Jelleine-I), TPFKLSLHL-NH(2) (Jelleine-II), EPFKLSLHL-NH(2) (Jelleine-III), and TPFKLSLH-NH(2) (Jelleine-IV) . The peptides were synthesized on-solid phase, purified and submitted to different biological assays: antimicrobial activity, mast cell degranulating activity and hemolysis . The Jelleines-I-III presented exclusively antimicrobial activities against yeast, Gram+ and Gram- bacteria; meanwhile, Jelleine-IV was not active in none of the assays performed . These peptides do not present any similarity with the other antimicrobial peptides from the honeybees; they are produced constitutively by the workers and secreted into Royal Jelly.

Bioorg Med Chem Lett, 2004 Jul 16, 14(14), 3733 - 8
Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents; Yao S et al.; Glyco-optimization (OPopS) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives . Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs) . Among them, compounds 8b,g,i,l, and 8u with 2"-amino, 2",3"-diamino, 2",4"-diamino, 3",4"-diamino, 3"-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(-) bacteria . Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1-2 microg/mL range.

Recenti Prog Med, 2004 May, 95(5), 265 - 75
{Lipodystrophy and lipid metabolism alterations in HIV-infected patients receiving highly active antiretroviral therapy (HAART)}; Calza L et al.; A wide range of morphologic alterations and lipid metabolism abnormalities have been recently described in HIV-infected patients receiving a protease inhibitor-based highly active antiretroviral therapy . The hyperlipidaemia may involve up to 70-80% of HIV-positive subjects treated with a protease inhibitor-containing regimen, and it is frequently (but not always) associated with the fat redistribution syndrome or lipodystrophy . The potential clinico-pathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations reported an increased risk of prematury coronary artery diseases in young HIV-positive individuals receiving protease inhibitors, besides peripheral atherosclerosis and acute pancreatitis . A hypolipidaemic diet and regular physical exercise may act favourably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or pesists for a long time . The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance.

Arch Pharm Res, 2004 May, 27(5), 471 - 7
Synthesis and biological evaluation of new thiazolopyrimidines; Said M et al.; In this study, a series of 4-amino-5-cyano-3-substituted-2,3-dihydrothiazol-2-thiones (1a-c), as well as their triazolo and triazinopyrimidine derivatives such as 8-substituted-3-benzyl-5-methylthiazolo{5,4-e}{1,2,4} triazolo{1,5-c}pyrimidin-2-thiones (4-6, 10) and 3-benzyl-5-methyl thiazolo{5,4-e}pyrimidino{3,4-b}{1,2,4}triazin-2-thiones (7a-b) were prepared as potential antimicrobial and antitumor agents . Some of the tested compounds showed promising antimicrobial activity and non of them showed any appreciable antitumor activity.

Curr Opin Rheumatol, 2004 Jul, 16(4), 411 - 8
Pattern recognition receptors and their involvement in the pathogenesis of arthritis; Seibl R et al.; PURPOSE OF REVIEW: Pattern recognition receptors are germ-line encoded receptors that recognize specific pathogen-associated molecules, thereby allowing the innate immune system to distinguish self from nonself structures . Pattern recognition receptors mediate activation of different signaling pathways, resulting in the production of proinflammatory cytokines and the expression of antimicrobial genes . Additionally, pattern recognition receptors play a central role in the activation and direction of the adaptive immune response . This review summarizes recent advances in research trying to elucidate the link between different pattern recognition receptors and inflammatory autoimmune disorders . RECENT FINDINGS: The best known pattern recognition receptors, the toll-like receptors, are involved in the regulation of inflammation during infectious diseases . They affect apoptotic pathways and dendritic cell maturation, and interact with B-cell receptors in priming T-cell responses to host-derived DNA . This brought toll-like receptors and other pattern recognition receptors into focus as potential players in the induction of autoimmune diseases . Indeed, several inflammatory autoimmune diseases have been linked during the past few years to defects or polymorphisms of genes encoding pattern recognition receptors . SUMMARY: The discovery of toll-like receptors and other groups of pattern recognition receptors, such as the caspase recruitment domains or the triggering receptors expressed by myeloid cells, allowed one to draw an increasingly complex picture of immune responses to pathogens . The growing evidence for an involvement of pattern recognition receptors in the pathogenesis of autoimmune disorders warrants further investigation of the expression and function of pattern recognition receptors to develop novel therapeutics for diseases such as rheumatoid arthritis.

J Antimicrob Chemother, 2004 Jul, 54(1), 29 - 37 Epub 2004 Jun 16.
Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systematic review and meta-analysis of randomized trials; Vidal L et al.; CONTEXT: Neutropenia is one of the grave consequences of cancer chemotherapy, and the treatment of neutropenic febrile patients with intravenous (iv) antibiotics has been shown to reduce mortality . Oral therapy could be an alternative approach for selected patients . OBJECTIVES: To compare the efficacy of oral antibiotics versus iv antibiotic therapy in febrile neutropenic cancer patients . DATA SOURCES: The Cochrane Library, the Cochrane Cancer Network Register of trials, EMBASE, LILACS and MEDLINE, databases for ongoing trials and the conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) . STUDY SELECTION: Randomized controlled trials comparing oral antibiotic/s and iv antibiotic/s for the treatment of neutropenic cancer patients with fever . DATA COLLECTION: Two reviewers independently assessed trial eligibility, methodological quality and extracted all data . Data concerning mortality, treatment failures and adverse events were drawn from included studies assuming an 'intention-to-treat' and 'per-protocol' basis for the outcome measures whenever possible . Relative risks (RR) with their 95% confidence intervals (CI) for dichotomous data were estimated . MAIN RESULTS: Fifteen trials (median mortality 0, range 0%-8.8%) were included in the analyses . The mortality rate was similar comparing oral and iv antibiotic treatment (RR 0.83, 95% CI 0.49-1.41, 2224 patients) . Treatment failure rates were also similar (RR 0.94, 95% CI 0.84-1.05, 15 trials) . No significant heterogeneity was shown for the primary outcomes . This effect was stable in a wide range of patients . Quinolones alone or combined with other antibiotics were used with comparable results . Adverse reactions, mostly gastrointestinal, were more common with oral antibiotics . CONCLUSIONS: Oral antibiotics may be safely offered to neutropenic patients with fever who are at low risk for mortality.

Immunol Rev, 2004 Apr, 198, 249 - 66
Innate immunity in plants and animals: striking similarities and obvious differences; Nurnberger T et al.; Innate immunity constitutes the first line of defense against attempted microbial invasion, and it is a well-described phenomenon in vertebrates and insects . Recent pioneering work has revealed striking similarities between the molecular organization of animal and plant systems for nonself recognition and anti-microbial defense . Like animals, plants have acquired the ability to recognize invariant pathogen-associated molecular patterns (PAMPs) that are characteristic of microbial organisms but which are not found in potential host plants . Such structures, also termed general elicitors of plant defense, are often indispensable for the microbial lifestyle and, upon receptor-mediated perception, inevitably betray the invader to the plant's surveillance system . Remarkable similarities have been uncovered in the molecular mode of PAMP perception in animals and plants, including the discovery of plant receptors resembling mammalian Toll-like receptors or cytoplasmic nucleotide-binding oligomerization domain leucine-rich repeat proteins . Moreover, molecular building blocks of PAMP-induced signaling cascades leading to the transcriptional activation of immune response genes are shared among the two kingdoms . In particular, nitric oxide as well as mitogen-activated protein kinase cascades have been implicated in triggering innate immune responses, part of which is the production of antimicrobial compounds . In addition to PAMP-mediated pathogen defense, disease resistance programs are often initiated upon plant-cultivar-specific recognition of microbial race-specific virulence factors, a recognition specificity that is not known from animals.

Immunol Rev, 2004 Apr, 198, 59 - 71
The immune response of Drosophila melanogaster; Leclerc V et al.; The response of the fruit fly Drosophila melanogaster to various microorganism infections relies on a multilayered defense . The epithelia constitute a first and efficient barrier . Innate immunity is activated when microorganisms succeed in entering the body cavity of the fly . Invading microorganisms are killed by the combined action of cellular and humoral processes . They are phagocytosed by specialized blood cells, surrounded by toxic melanin, or lysed by antibacterial peptides secreted into the hemolymph by fat body cells . During the last few years, research has focused on the mechanisms of microbial recognition by various pattern recognition receptors and of the subsequent induction of antimicrobial peptide expression . The cellular arm of the Drosophila innate immune system, which was somehow neglected, now constitutes the new frontier.

Vestn Khir Im I I Grek, 2004, 163(2), 69 - 71
{Surgical strategy for wounds of the cervical part of the esophagus}; Mikhailov AP et al.; An analysis of results of treatment of 425 patients aged from 15 to 85 years with penetrating wounds of the neck was made . In 40 (8.1%) patients there were wounds of the cervical part of the esophagus, 29 of them had associated injuries . The proposed active surgical strategy consisted in a necessary thorough revision of the penetrating wounds of the neck using general anesthesia and then directly in the operation room using subsidiary methods of examination such as urgent x-ray analysis with a water-soluble contrast, esophagoscopy, larengotracheoscopy . This approach allowed detection of injuries of the cervical part of the esophagus, even in cases of the absence of clinical symptoms of esophagus injuries . In all the patients the wounds of the esophagus were sutured and followed by active aspiration drainage and antibacterial treatment with modern antimicrobial medicines.

Cell Mol Life Sci, 2004 Jun, 61(12), 1507 - 19
Antimicrobial peptide induction in the haemolymph of the Mexican scorpion Centruroides limpidus limpidus in response to septic injury; Rodriguez de la Vega RC et al.; Antimicrobial peptides (AMPs) are essential components of host defences against infectious microrganisms . In chelicerate organisms they have been implicated in three alternative defensive systems: one is defined by the immediate up-regulation of genes encoding AMPs, another is characterized by the inducible systemic release of AMPs from cellular reservoirs and the third alternative is the systemic constitutive production of AMPs . In this work we used a differential high-performance liquid chromatography and mass spectrometry approach to show that septic injury elicits an immune response in the haemolymph of the Mexican scorpion Centruroides limpidus limpidus . We isolated several haemolymph components, one of which was characterized extensively (amino acid sequence, disulphide pairing, cDNA and genomic clones) and demonstrated to be a novel member of the invertebrate defensin family and consequently named C . limpidus limpidus defensin-like peptide (Cll-dlp) . This peptide accumulates in the haemolymph in response to septic injury, independently of transcriptional regulation.

Ann Intern Med, 2004 Jun 15, 140(12), 1037 - 51
Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group; Waselenko JK et al.; Physicians, hospitals, and other health care facilities will assume the responsibility for aiding individuals injured by a terrorist act involving radioactive material . Scenarios have been developed for such acts that include a range of exposures resulting in few to many casualties . This consensus document was developed by the Strategic National Stockpile Radiation Working Group to provide a framework for physicians in internal medicine and the medical subspecialties to evaluate and manage large-scale radiation injuries . Individual radiation dose is assessed by determining the time to onset and severity of nausea and vomiting, decline in absolute lymphocyte count over several hours or days after exposure, and appearance of chromosome aberrations (including dicentrics and ring forms) in peripheral blood lymphocytes . Documentation of clinical signs and symptoms (affecting the hematopoietic, gastrointestinal, cerebrovascular, and cutaneous systems) over time is essential for triage of victims, selection of therapy, and assignment of prognosis . Recommendations based on radiation dose and physiologic response are made for treatment of the hematopoietic syndrome . Therapy includes treatment with hematopoietic cytokines; blood transfusion; and, in selected cases, stem-cell transplantation . Additional medical management based on the evolution of clinical signs and symptoms includes the use of antimicrobial agents (quinolones, antiviral therapy, and antifungal agents), antiemetic agents, and analgesic agents . Because of the strong psychological impact of a possible radiation exposure, psychosocial support will be required for those exposed, regardless of the dose, as well as for family and friends . Treatment of pregnant women must account for risk to the fetus . For terrorist or accidental events involving exposure to radioiodines, prophylaxis against malignant disease of the thyroid is also recommended, particularly for children and adolescents.

Ann Clin Microbiol Antimicrob . 2004 Jun 14;3(1):11.
Physician behaviour for antimicrobial prescribing for paediatric upper respiratory tract infections: a survey in general practice in Trinidad, West Indies; Mohan S et al.; BACKGROUND: Upper respiratory tract infections (URTIs) are among the most frequent reasons for physician office visits in paediatrics . Despite their predominant viral aetiology, URTIs continue to be treated with antimicrobials . We explored general practitioners' (GPs) prescribing behaviour for antimicrobials in children (</= 16 years) with URTIs in Trinidad, using the guidelines from the Centers for Disease Control and Prevention (CDC) as a reference . METHODS: A cross-sectional study was conducted on 92 consenting GPs from the 109 contacted in Central and East Trinidad, between January to June 2003 . Using a pilot-tested questionnaire, GPs identified the 5 most frequent URTIs they see in office and reported on their antimicrobial prescribing practices for these URTIs to trained research students . RESULTS: The 5 most frequent URTIs presenting in children in general practice, are the common cold, pharyngitis, tonsillitis, sinusitis and acute otitis media (AOM) in rank order . GPs prescribe at least 25 different antibiotics for these URTIs with significant associations for amoxicillin, co-amoxiclav, cefaclor, cefuroxime, erythromycin, clarithromycin and azithromycin (p < 0.001) . Amoxicillin alone or with clavulanate was the most frequently prescribed antibiotic for all URTIs . Prescribing variations from the CDC recommendations were observed for all URTIs except for AOM (50%), the most common condition for antibiotics . Doctors practicing for >30 years were more likely to prescribe antibiotics for the common cold (p = 0.014) . Severity (95.7%) and duration of illness (82.5%) influenced doctors' prescribing and over prescribing in general practice was attributed to parent demands (75%) and concern for secondary bacterial infections (70%) . Physicians do not request laboratory investigations primarily because they are unnecessary (86%) and the waiting time for results is too long (51%) . CONCLUSIONS: Antibiotics are over prescribed for paediatric URTIs in Trinidad and amoxicillin with co-amoxiclav were preferentially prescribed . Except for AOM, GPs' prescribing varied from the CDC guidelines for drug and duration . Physicians recognise antibiotics are overused and consider parents expecting antibiotics and a concern for secondary bacterial infections are prescribing pressures . Guidelines to manage URTIs, ongoing surveillance programs for antibiotic resistance, public health education on non-antibiotic strategies, and postgraduate education for rational pharmacotherapy in general practice would decrease inappropriate antibiotic use in URTIs.

Biochem J, 2004 Nov 15, 384(Pt 1), 25 - 36
Structure, conformation and biological activity of a novel lipodepsipeptide from Pseudomonas corrugata: cormycin A; Scaloni A et al.; Cationic lipodepsipeptides from Pseudomonas spp . have been characterized for their structural and antimicrobial properties . In the present study, the structure of a novel lipodepsipeptide, cormycin A, produced in culture by the tomato pathogen Pseudomonas corrugata was elucidated by combined protein chemistry, mass spectrometry and two-dimensional NMR procedures . Its peptide moiety corresponds to L-Ser-D-Orn-L-Asn-D-Hse-L-His-L-aThr-Z-Dhb-L-Asp(3-OH)-L-Thr(4-Cl) {where Orn represents ornithine, Hse is homoserine, aThr is allo-threonine, Z-Dhb is 2,3-dehydro-2-aminobutanoic acid, Asp(3-OH) is 3-hydroxyaspartic acid and Thr(4-Cl) is 4-chlorothreonine}, with the terminal carboxy group closing a macrocyclic ring with the hydroxy group of the N-terminal serine residue . This is, in turn, N-acylated by 3,4-dihydroxy-esadecanoate . In aqueous solution, cormycin A showed a rather compact structure, being derived from an inward orientation of some amino acid side chains and from the 'hairpin-bent' conformation of the lipid, due to inter-residue interactions involving its terminal part . Cormycin was significantly more active than the other lipodepsipeptides from Pseudomonas spp., as demonstrated by phytotoxicity and antibiosis assays, as well as by red-blood-cell lysis . Differences in biological activity were putatively ascribed to its weak positive net charge at neutral pH . Planar lipid membrane experiments showed step-like current transitions, suggesting that cormycin is able to form pores . This ability was strongly influenced by the phospholipid composition of the membrane and, in particular, by the presence of sterols . All of these findings suggest that cormycin derivatives could find promising applications, either as antifungal compounds for topical use or as post-harvest biocontrol agents.

Biotechnol Lett, 2004 May, 26(9), 735 - 9
A short alpha-helical antimicrobial peptide with antibacterial selectivity; Shin SY et al.; A 13-residue alpha-helical peptide (K6L5WP), designed from Leu6-->Pro substitution of a hemolytic alpha-helical peptide (K6L6W), exhibited strong antibacterial activity (MIC: 2 to approximately 4 microM against three gram-positives and three gram-negatives) comparable to that of melittin but had no hemolytic activity . Tryptophan fluorescence studies indicated bacterial selectivity of K6L5WP is closely related to the selective interaction with negatively charged phospholipids on the surface of bacterial cells . These results suggested that the central Pro6 in K6L5WP plays an important role in its bacterial cell selectivity . In conclusion, K6L5WP with antibacterial selectivity may serve as an attractive candidate for the development of antimicrobial agents.

Food Addit Contam, 2004 Mar, 21(3), 216 - 21
Meeting maximum residue limits: an improved screening technique for the rapid detection of antimicrobial residues in animal food products; Stead S et al.; A rapid, high-throughput antimicrobial screening assay was developed using either a physical fluid extraction or a solvent extraction technique coupled to the commercially available PremiTest . The solvent extraction approach was fully validated for a wide range of tissues and the fluid extraction approach partially validated for porcine muscle . Both procedures can detect a wide range of antimicrobial compounds at or below maximum residue limit concentrations . The use of a solvent extraction provides an enhanced test capable of detecting a wider range of drugs than the fluid extraction approach at or below half maximum residue limit levels in a variety of matrices . Biochemical methods for the class-specific identification of beta-lactams and sulphonamides following initial screening were developed and validated . The approach is a significant improvement on existing methodologies as a tool for residues monitoring in surveillance programmes.

Pediatr Infect Dis J, 2004 Jun, 23(6), 485 - 9
Postlicensure surveillance for pneumococcal invasive disease after use of heptavalent pneumococcal conjugate vaccine in Northern California Kaiser Permanente; Black S et al.; OBJECTIVE: To assess the direct and indirect effects of the introduction of routine use of pneumococcal conjugate vaccine in infants and toddlers at risk for invasive disease caused by vaccine serotypes and nonvaccine serotypes in vaccinated children and unvaccinated children of the same age . Secondary objectives included determination of the risk of pneumococcal infections in unvaccinated older children and adults in the same population and the impact of vaccine introduction on patterns of antimicrobial resistance . METHODS: Northern California Kaiser Permanente provides integrated comprehensive care to 3.1 million people and has an annual birth cohort of 38,000 infants . Microbiology services use a regional laboratory . Automated laboratory results, immunization records as well as diagnoses for inpatient and outpatient utilization are available from clinical data bases . Beginning in April 2000, the heptavalent pneumococcal conjugate (PNCV7) vaccine was introduced into routine use in the Northern California Kaiser Permanente population . Cases of invasive pneumococcal disease were identified from the automated hospital diagnosis as well as laboratory databases for all individuals, vaccinees and nonvaccinees, inpatient and outpatient . For the purpose of these analyses, pneumococcal invasive disease was defined as a positive culture from a normally sterile site . RESULTS: As of March 2003, 157,471 children had received 1 dose or more of PNCV7, but only 24% of those <2 years of age received all 4 doses as a result of shortages of vaccine . During the last year of observation, no cases of vaccine serotype disease were seen in children <1 year of age compared with an incidence ranging between 51.5 and 98.2 cases per 100,000 person-years (16-34 cases per year) in the years before vaccine introduction . Similar reductions were seen in children <5 years of age . There was no evidence of any concomitant increase in pneumococcal disease caused by nonvaccine serotypes . High level resistance of pneumococci to penicillin fell from a peak of 15% in 2000 to 5% in the first half of 2003 . Similar trends were seen for other antibiotics . CONCLUSION: The PNCV7 vaccine is highly effective in reducing the burden of pneumococcal disease in children <5 years of age, and there is evidence of a herd effect as well as a decrease in the antibiotic resistant in strains causing disease . For invasive disease, there is no current evidence of serotype replacement.

Biochem Biophys Res Commun, 2004 Jul 9, 319(4), 1292 - 8
Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori; Han C et al.; Helicobacter pylori is a gram-negative pathogenic bacterium, which is associated with peptic ulcer disease and gastric cancer . It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen . In bacteria, peptide deformylase (PDF) catalyzes the removal of a formyl group from the N-termini of nascent polypeptides . Due to its essentiality and absence in mammalian cells, PDF has been considered as an attractive target for the discovery of novel antibiotics . In this work, a new PDF gene (def) from H . pylori strain SS1 was cloned, expressed, and purified in Escherichia coli system . Sequence alignment shows that H . pylori PDF (HpPDF) shares about 40% identity to E . coli PDF (EcPDF) . The enzymatic properties of HpPDF demonstrate its relatively high activity toward formyl-Met-Ala-Ser, with K(cat) of 3.4s(-1), K(m) of 1.7 mM, and K(cat) / K(m) of 2000M(-1)s(-1) . HpPDF enzyme appears to be fully active at pH between 8.0 and 9.0, and temperature 50 degrees C . The enzyme activity of Co(2+)-containing HpPDF is apparently higher than that of Zn(2+)-containing HpPDF . This present work thereby supplies a potential platform that facilitates the discovery of novel HpPDF inhibitors and further of possible antimicrobial agents against H . pylori.

Transplant Proc, 2004 May, 36(4), 1147 - 8
Microbial surveillance during human pancreatic islet isolation; Bucher P et al.; OBJECTIVES: The study aim was to investigate the microbiological safety of islet isolation and transplantation . MATERIALS AND METHODS: Between 1996 and 2002, prospective microbiological screening was performed on all pancreata procured for islet transplantation . Pancreas transport media and postpurification preparations were screened for microbiological contamination . Prior to isolation, pancreata were washed with either Hanks solution (group I, n = 170) or decontaminated with antiseptic and antimicrobial drugs (group II, n = 45) . RESULTS: Microbiological contamination of the pancreas preservation media was shown in 62% . Analysis of the contaminants showed 74% gram-positive, 21% gram-negative organisms, and 5% fungi . The donor condition or procurement center did not influence the contamination rate . Longer pancreas transport duration was significantly associated with bacterial contamination (P <.05) . In group I, 16 (9.4%) of 170 islet preparations presented microbial contamination at the end of the isolation procedures . Gram-positive organisms were present in 10 (6%), gram-negative organisms in 4 (2.4%), and fungi in 2 (1.2%) preparations . Four islet preparations (2.4%) from pancreata with noninfected transport medium were positive on postpurification cultures, all with gram-positive organisms . In group II, only 2 of 45 islet preparations (4.4%) presented microbial contamination at the end of the isolation process . CONCLUSIONS: The rate of microbial contamination during pancreas procurement and transport is high . Significant contaminants present when beginning islet isolation become undetectable by the conclusion of isolation . Diminishing the bio-burden by pancreas decontamination reduces the risk of contamination of the final islet preparation.

Microb Pathog, 2004 Jul, 37(1), 21 - 7
Differential expression of sheep beta-defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia; Ackermann MR et al.; Beta-defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes . Expression of some beta-defensins is increased by bacterial-induced inflammatory responses whereas expression of other beta-defensins is constitutive . Two beta-defensins are expressed in lungs of sheep (sheep beta-defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection . The effect of Mannheimia haemolytica, a Gram-negative bacteria known to induce expression of bovine beta-defensins and NF-kappa B in lung, has not been determined for SBD-1/-2 . In this study, different concentrations of M . haemolytica were inoculated into pulmonary bronchi of lambs . SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase . In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10(9)) . In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M . haemolytica concentrations . Co-inoculation of M . haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8 . SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes . This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection.

Int J Antimicrob Agents, 2004 Jun, 23(6), 563 - 71
New real-time PCR-based method for in vitro susceptibility testing of Anaplasma phagocytophilum against antimicrobial agents; Hunfeld KP et al.; Up to now, only a few isolates of Anaplasma phagocytophilum have been tested for their susceptibility against a small number of antimicrobial agents . In addition, as with other fastidious or intracellular bacteria, the test methods are laborious and neither minimal inhibitory concentration (MIC) definitions, nor the test conditions and the inocula are standardised to date . A new 16S-rDNA-based real-time PCR assay has been developed and used under standardised conditions to analyse the activity of seven antimicrobial agents against two A . phagocytophilum isolates . After 72 h incubation, MICs were determined by software-assisted calculation of bacterial growth in samples and controls from semi-quantitative PCR results . In our study, the rank order of potency on a mg/l basis for the antimicrobial agents with enhanced in vitro activity against A . phagocytophilum was moxifloxacin (MIC: < or = 0.03 mg/l) > doxycycline (MIC: < or = 0.125 mg/l) > ciprofloxacin (MIC: 0.125 mg/l) . Gentamicin, ampicillin, azithromycin and cethromycin showed no activity against the isolates tested in this investigation . Our new 16S-rDNA-PCR-based microdilution test system was shown to be sensitive, reproducible and reliable . The assay is capable of testing larger numbers of isolates and antimicrobial agents under standardised and very precise test conditions and may therefore offer a competent technical solution of the difficulties known to be associated with in vitro testing of other bacterial pathogens that grow intracellularly, such as chlamydia or rickettsia .

Int J Antimicrob Agents, 2004 Jun, 23(6), 556 - 62
Integrons and beta-lactamases--a novel perspective on resistance; Weldhagen GF; The understanding of microbial resistance to the beta-lactam class of antibiotics in the form of beta-lactamases has come a long way since the early discoveries of narrow-spectrum penicillinases . Integron-borne beta-lactamases co-occurring with a wide array of non-beta-lactam resistance genes, particularly pose an increasing threat to the nosocomial environment, giving rise to multi-drug resistant microbes with complex resistance patterns . Selection of potent beta-lactamases through the use of non-beta-lactam agents may be possible through integron-mediated resistance . It has become imperative that we should continuously strive to understand these complex mechanisms of antimicrobial resistance, not only to overcome them, but to avoid them from evolving further .

Life Sci, 2004 Jul 9, 75(8), 969 - 77
Cannabinoid receptor-independent suppression of the superoxide generation of human neutrophils (PMN) by CP55 940, but not by anandamide; Kraft B et al.; Cannabinoids have been shown to affect various immune functions . To date, almost no data exist on PMN, which provide the first line antimicrobial defense . The objective of the present study was to investigate the effects of the synthetic dibenzopyrane ligand CP55 940, the endogenous cannabinoid anandamide and methanandamide on the "respiratory burst" of isolated human PMN in vitro . After preincubation with high micromolar concentrations of CP55 940, fMLP-stimulated PMN showed a reduction in superoxide production, whereas the spontaneous burst activity of resting PMN remained unaffected . This inhibitory effect of CP55 940 was not CB-receptor-mediated . In contrast, anandamide and methanandamide did not alter the oxidative microbicidal PMN function.

Virology, 2004 Jun 1, 323(2), 268 - 75
Inactivation of viruses infecting ectothermic animals by amphibian and piscine antimicrobial peptides; Chinchar VG et al.; The ability of five purified amphibian antimicrobial peptides (dermaseptin-1, temporin A, magainin I, and II, PGLa), crude peptide fractions isolated from the skin of Rana pipiens and R . catesbeiana, and four antimicrobial peptides (AMPs) from hybrid striped bass (piscidin-1N, -1H, -2, and -3) were examined for their ability to reduce the infectivity of channel catfish virus (CCV) and frog virus 3 (FV3) . All compounds, with the exception of magainin I, markedly reduced the infectivity of CCV . In contrast to CCV, FV3 was 2- to 4-fold less sensitive to these agents . Similar to an earlier study employing two other amphibian peptides, the agents used here acted rapidly and over a wide, physiologically relevant, temperature range to reduce virus infectivity . These results extend our previous findings and strongly suggest that various amphibian and piscine AMPs may play important roles in protecting fish and amphibians from pathogenic viruses.

Proc Natl Acad Sci U S A, 2004 Jun 22, 101(25), 9263 - 5 Epub 2004 Jun 10.
The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes; Lee P et al.; The antimicrobial peptide hepcidin appears to play a central role in the regulation of iron homeostasis . In intact animals, iron overload or the injection of lipopolysaccharide (LPS) stimulates transcription of HAMP, the gene that encodes hepcidin . In isolated hepatocytes, IL-6, an inflammatory cytokine the production of which is stimulated by LPS, up-regulates transcription of hepcidin . In contrast, iron has no stimulatory effect on hepcidin expression in isolated hepatocytes . There is apparently a signaling pathway, activated by iron, that is present in the intact animal but not in isolated hepatocytes . Studies in humans and mice have shown that this iron-dependent pathway requires the presence of Hfe, hemojuvelin, and probably transferrin receptor 2 (tfr-2) . To determine whether activation of hepcidin transcription by IL-6 also requires Hfe and tfr-2, we have studied mice homozygous for targeted disruption of HFE, beta(2)-microglobulin, and for a truncating mutation of TFR-2 . We show that these mutant mice react normally to injection of endotoxin and that their isolated hepatocytes react normally to IL-6 . This indicates that the signaling pathway activated by IL-6 does not require either Hfe or tfr-2 . Mice with disruption of the gene encoding IL-6 seem to have a blunted response to LPS, but the statistical significance of the small response documented is borderline . It is therefore not clear whether LPS stimulates secretion of cytokines other than IL-6 that may stimulate hepcidin transcription.

Adv Drug Deliv Rev, 2004 Jun 23, 56(10), 1497 - 521
Antimicrobial drug delivery in food animals and microbial food safety concerns: an overview of in vitro and in vivo factors potentially affecting the animal gut microflora; Yan SS et al.; This review provides an overview of considerations particular to the delivery of antimicrobial agents to food animals . Antimicrobial drugs are used in food animals for a variety of purposes . These drugs may have therapeutic effects against disease agents, or may cause changes in the structure and/or function of systems within the target animal . Routes of administration, quantity, duration, and potency of an antimicrobial drug are all important factors affecting their action(s) and success . Not only might targeted pathogens be affected, but also bacteria residing in (or on) the treated food animals, especially in the intestines (gastrointestinal tract microflora) . Resistance to antimicrobial agents can occur through a number of mechanisms . The extent to which resistance develops is greatly affected by the amount of drug {or its metabolite(s)} a bacterium is exposed to, the duration of exposure, and the interaction between an individual antimicrobial agent and a particular bacterium . The impact of antimicrobial agents on the emergence of resistance in vitro and in vivo may not readily correlate.

Clin Microbiol Infect, 2004 Jun, 10(6), 502 - 11
Optimal use of antibiotic resistance surveillance systems; Critchley IA et al.; Increasing concern about the emergence of resistance in clinically important pathogens has led to the establishment of a number of surveillance programmes to monitor the true extent of resistance at the local, regional and national levels . Although some programmes have been operating for several years, their true usefulness is only now being realised . This review describes some of the major surveillance initiatives and the way in which the data have been used in a number of different settings . In the hospital, surveillance data have been used to monitor local antibiograms and determine infection control strategies and antibiotic usage policies . In the community, surveillance data have been used to monitor public health threats, such as infectious disease outbreaks involving resistant pathogens and the effects of bioterrorism countermeasures, by following the effects of prophylactic use of different antibiotics on resistance . Initially, the pharmaceutical industry sponsored surveillance programmes to monitor the susceptibility of clinical isolates to marketed products . However, in the era of burgeoning resistance, many developers of antimicrobial agents find surveillance data useful for defining new drug discovery and development strategies, in that they assist with the identification of new medical needs, allow modelling of future resistance trends, and identify high-profile isolates for screening the activity of new agents . Many companies now conduct pre-launch surveillance of new products to benchmark activity so that changes in resistance can be monitored following clinical use . Surveillance data also represent an integral component of regulatory submissions for new agents and, together with clinical trial data, are used to determine breakpoints . It is clear that antibiotic resistance surveillance systems will continue to provide valuable data to health care providers, university researchers, pharmaceutical companies, and government and regulatory agencies.

J Antimicrob Chemother, 2004 Jul, 54(1), 221 - 4 Epub 2004 Jun 09.
Antibiotic usage in intensive care units: a pharmaco-epidemiological multicentre study; Malacarne P et al.; OBJECTIVES: To prospectively assess the use of antibiotics in ICUs . PATIENTS AND METHODS: A total of 979 critically ill patients over 14 years of age were recruited in 43 Italian ICUs . For each patient, admission and discharge characteristics, information on the drugs administered, use of antibiotic susceptibility tests (ASTs), presence and severity of sepsis were collected daily until discharge or for a maximum of 21 days . RESULTS: Most patients with sepsis (99%) received antibiotics, and in almost all (93%) the treatment was started empirically, with broad-spectrum antibiotics . ASTs followed the onset of empirical treatment in 93% of cases . De-escalation was carried out in 16 patients, while in 37.6% of cases an antibiotic had to be changed or added . Antibiotic prophylaxis in surgical patients involved widespread use of drug combinations (31% of cases) and lasted 3 days on average . In non-surgical patients antibiotic prophylaxis lasted 4.6 days and in 42% a third-generation cephalosporin was used . CONCLUSIONS: We found an appropriate approach to the therapeutic use of antibiotics: early empirical onset with broad-spectrum antimicrobial, followed by ASTs in order to target the therapy . However, in more than one-third of the cases the first-line choice was inappropriate . As regards prophylaxis, both surgical and non-surgical patients tended to have excessive duration of treatment, with widespread use of antibiotic combinations, too often involving a third-generation cephalosporin or carbapenem . This indicates a wide gap between clinical guidelines and clinical practice that calls for close assessment.

Biophys J, 2004 Jun, 86(6), 3759 - 71
Structure of supported bilayers composed of lipopolysaccharides and bacterial phospholipids: raft formation and implications for bacterial resistance; Tong J et al.; Lipopolysaccharide (LPS), the major lipid on the surface of Gram-negative bacteria, plays a key role in bacterial resistance to hydrophobic antibiotics and antimicrobial peptides . Using atomic force microscopy (AFM) we characterized supported bilayers composed of LPSs from two bacterial chemotypes with different sensitivities to such antibiotics and peptides . Rd LPS, from more sensitive "deep rough" mutants, contains only an inner saccharide core, whereas Ra LPS, from "rough" mutants, contains a longer polysaccharide region . A vesicle fusion technique was used to deposit LPS onto either freshly cleaved mica or polyethylenimine-coated mica substrates . The thickness of the supported bilayers measured with contact-mode AFM was 7 nm for Rd LPS and 9 nm for Ra LPS, consistent with previous x-ray diffraction measurements . In water the Ra LPS bilayer surface was more disordered than Rd LPS bilayers, likely due to the greater volume occupied by the longer Ra LPS polysaccharide region . Since deep rough mutants contain bacterial phospholipid (BPL) as well as LPS on their surfaces, we also investigated the organization of Rd LPS/BPL bilayers . Differential scanning calorimetry and x-ray diffraction indicated that incorporation of BPL reduced the phase transition temperature, enthalpy, and average bilayer thickness of Rd LPS . For Rd LPS/BPL mixtures, AFM showed irregularly shaped regions thinner than Rd LPS bilayers by 2 nm (the difference in thickness between Rd LPS and BPL bilayers), whose area increased with increasing BPL concentration . We argue that the increased permeability of deep rough mutants is due to structural modifications caused by BPL to the LPS membrane, in LPS hydrocarbon chain packing and in the formation of BPL-enriched microdomains.

J Vet Pharmacol Ther, 2004 Jun, 27(3), 129 - 38
Idiosyncratic toxicity associated with potentiated sulfonamides in the dog; Trepanier LA; Idiosyncratic toxicity to potentiated sulfonamides occurs in both humans and dogs, with considerable clinical similarities . The syndrome in dogs can consist of fever, arthropathy, blood dyscrasias (neutropenia, thrombocytopenia, or hemolytic anemia), hepatopathy consisting of cholestasis or necrosis, skin eruptions, uveitis, or keratoconjunctivitis sicca . Other manifestations seen less commonly include protein-losing nephropathy, meningitis, pancreatitis, pneumonitis, or facial nerve palsy . The pathogenesis of these reactions is not completely understood, but may be due to a T-cell-mediated response to proteins haptenated by oxidative sulfonamide metabolites . Our laboratory is working on tests to characterize dogs with possible idiosyncratic sulfonamide reactions, to include ELISA for anti-drug antibodies, immunoblotting for antibodies directed against liver proteins, flow cytometry for drug-dependent anti-platelet antibodies, and in vitro cytotoxicity assays . The management of idiosyncratic sulfonamide toxicity involves client education to identify clinical signs early and allow rapid drug discontinuation, supportive care to include possibly ascorbate and glutathione precursors, and avoidance of subsequent re-exposure . It is important to realize that only antimicrobial sulfonamides, such as sulfamethoxazole, sulfadiazine, and sulfadimethoxine, share this clinical syndrome . There is no evidence for cross-reactivity with drugs that have different underlying structures but share a sulfonamide moiety, such as acetazolamide, furosemide, glipizide, or hydrochlorthiazide.

Annu Rev Biochem, 2004, 73, 241 - 68
ATP-binding cassette transporters in bacteria; Davidson AL et al.; ATP-binding cassette (ABC) transporters couple ATP hydrolysis to the uptake and efflux of solutes across the cell membrane in bacteria and eukaryotic cells . In bacteria, these transporters are important virulence factors because they play roles in nutrient uptake and in secretion of toxins and antimicrobial agents . In humans, many diseases, such as cystic fibrosis, hyperinsulinemia, and macular dystrophy, are traced to defects in ABC transporters . Recent advances in structural determination and functional analysis of bacterial ABC transporters, reviewed herein, have greatly increased our understanding of the molecular mechanism of transport in this transport superfamily.

Antonie Van Leeuwenhoek, 2000 Apr, 77(3), 197 - 207
Antimicrobial peptides derived from heme-containing proteins: hemocidins; Mak P et al.; Deprived of heme and partially unfolded hemoglobin, myoglobin and cytochrome c display microbicidal activity against a broad spectrum of microorganisms with half maximal lethal dose estimated at micromolar concentrations . The intact proteins were ineffective . Antibacterial activity of these apohemoproteins was also sustained after digestion to approximately 50 amino acids long peptides but further fragmentation abolished microbicidal properties . The most active fragment of apomyoglobin (corresponding to 56-131 region) showed a pronounced effect on the E . coli membrane permeabilization and its action was sensitive to salt as well as to divalent cations concentrations . The membrane-directed effect was specific toward bacteria but no lipopolysaccharide binding properties were observed . No hemolytic properties, even at high peptide concentrations were found; however, a slight but dose-independent cytotoxic effect was observed on fibroblasts and hepatoma cells . The presented data suggest a 'carpet-like' mechanism of the membrane-directed activity and may result from exceptional abilities of hemoprotein-derived peptides to form alpha-helical structures . We postulate that the antimicrobial peptides obtained from the heme-containing proteins should be named hemocidins, in contrast to, e.g., hemorphins displaying opioid-like activity.

Berl Munch Tierarztl Wochenschr, 2004 May-Jun, 117(5-6), 177 - 81
Principles, application areas and an example of risk assessment conducted at the Danish Institute for Food and Veterinary Research; Greiner M et al.; The Department for Epidemiology and Risk Analysis at the Danish Institute for Food and Veterinary Research (DFVF) is concerned with risk analyses in the areas of food safety, zoonoses, antimicrobial resistance and OIE (World Organisation for Animal Health) list A and B diseases . The DFVF is responsible for the risk assessment component of the risk analysis process and provides advice and support for the risk management and risk communication component, which is generally under the auspices of the Danish Veterinary and Food Administration (DVFA) . The paper presents guidelines for the conduct of risk assessments at the DFVF . Important elements of these guidelines are the independence between risk assessment and risk management, the commitment to science-based, transparent and fully documented procedures and adherence to a protocol that regulates the cooperation between DFVF and DVFA . Typical steps of a quantitative risk assessment are the description of the risk scenario, information retrieval, mathematical modelling with stochastic simulation, final risk estimation with a sensitivity analysis and reporting . The procedure is exemplified using a Monte Carlo simulation model for the assessment of the risk of BSE transmission to calves by tallow-based calf milk replacer.

Infection, 2004 Jun, 32(3), 157 - 62
Update on glycopeptide use in german university hospitals; Kern WV et al.; BACKGROUND: A previous study has shown considerable variation in glycopeptide use from 1992 through 1994 among four university hospitals in southern Germany . Active antimicrobial management in one of the hospitals was associated with the containment of glycopeptide consumption in the medical and surgical service at < 1.5 defined daily doses (DDD)/100 patient days in the subsequent period . In the present study, more recent data on comparative glycopeptide use in German university hospitals were analyzed . MATERIALS AND METHODS: Hospital pharmacy records from 1998 through 2000 were evaluated . The number of DDD (definition according to the World Health Organization {WHO}/Anatomic and Therapeutic Classification {ATC} index) per 100 patient days was calculated to compare glycopeptide use in different medical and surgical service areas between eight German university hospitals . RESULTS: The 3-year averages in recent glycopeptide use for the eight hospitals ranged between 1.3 and 8.8 DDD/100 patient days in the medical services, and between 0.7 and 1.8 DDD/100 patient days in the surgical services . Only one of the eight hospitals showed medical service glycopeptide use of < 1.5 DDD/100 patient days . In most hospitals, glycopeptide use was higher in the medical intensive care units (ICU) (median 8.6; range 4.3 to 12 DDD/100 patient days, data for the year 2000) than in the surgical ICUs (median 6.7; range 1.2 to 8.6 DDD/100 patient days, data for the year 2000) . High use was also observed for hematology-oncology services (median 7.5; range 2.7 to 15.7 DDD/100 patient days, data for the year 2000) . CONCLUSION: These recent data from a larger hospital sample confirm large variations in glycopeptide use, identify hematology-oncology services as a significant prescribing source along with ICUs, and indicate areas of probable overuse of glycopeptide antibiotics . The data may be useful as a benchmark for further focused drug use control interventions . Copyright Urban and Vogel

Rev Port Pneumol, 2003 Sep-Oct, 9(5), 435 - 61
{Portuguese Respiratory Society guidelines for the management of community--acquired pneumonia in immunocompetent adults}; Sociedade Portuguesa de Pneumologia; Comissao de Infecciologia Respiratoria; The Portuguese Respiratory Society makes a series of recommendations as to the state of the art of the diagnostic, therapeutic and preventive approach to community-acquired pneumonia in immunocompetent adults in Portugal . These proposals should be regarded as general guidelines and are not intended to replace the clinical sense used in resolving each individual case . Our main goal is to stratify the patients according to the risk of morbidity and mortality in order to justify the following decisions more rationally: the choice of place of treatment (outpatient or inpatient), diagnostic tests and antimicrobial therapy . We also make a set of recommendations for the prevention of CAP . We plan to conduct multi-centre prospective studies, preferably in collaboration with other scientific societies, in order to be able to characterise the situation in Portugal more accurately and regularly update this document.

J Trauma, 2004 Apr, 56(4), 863 - 6
Survival benefit conferred by topical antimicrobial preparations in burn patients: a historical perspective; Brown TP et al.; BACKGROUND: Topical antimicrobial agents have proven efficacy in preventing life-threatening invasive burn wound infection . Under wartime or mass-casualty conditions, however, there may be an inadequate supply of these agents . This study aimed to identify those patients most likely to benefit therefrom . METHODS: Logistical regression analysis of data from the U.S . Army Burn Center was performed . Mortality data for the period immediately preceding the introduction of topical mafenide acetate (MA) (1950-1963) were compared with data for the subsequent period (1964-1968) . During the second period, MA was routinely applied but treatment was otherwise similar . The mortality decrement attributed to MA was determined for various ages and burn sizes . RESULTS: For patients of combatant age (20-50 years), MA was associated with a greater than 10% reduction in mortality for those with burns of 40-79% of the total body surface area (TBSA) . Only a minimal effect on mortality was noted for those patients with burns smaller than 40% or greater than 79% . CONCLUSIONS: When resources are limited, topical therapy (specifically, MA) is likely to confer the greatest survival benefit for combatants with burns of 40-79% TBSA.

Biol Pharm Bull, 2004 Jun, 27(6), 863 - 6
Antibacterial and antifungal effects of essential oils from coniferous trees; Hong EJ et al.; Essential oils have potential biological effects, i.e., antibiotic, anticarcinogenic, and sedative effects during stress . In the present study, we investigated the antibacterial and antifungal effects of essential oils extracted from the coniferous species Pinus densiflora, Pinus koraiensis, and Chamaecyparis obtusa, because their biological activities have not been yet elucidated . The essential oils were quantified using gas chromatography and identified in gas chromatography-mass spectrometric analysis . Simultaneously, antibacterial and antifungal assays were performed using the essential oils distilled from the needles of coniferous trees . The major components and the percentage of each essential oil were: 19.33% beta-thujene in P . densiflora; 10.49% alpha-pinene in P . koraiensis; 10.88% bornyl acetate in C . obtusa . The essential oils from P . densiflora and C . obtusa have antibacterial effects, whereas essential oils from P . koraiensis and C . obtusa have antifungal effects . These results indicate that the essential oils from the three coniferous trees, which have mild antimicrobial properties, can inhibit the growth of gram-positive and gram-negative bacteria and fungi.

Bioorg Med Chem, 2004 Jul 1, 12(13), 3503 - 19
Novel ketolide antibiotics with a fused five-membered lactone ring--synthesis, physicochemical and antimicrobial properties; Hunziker D et al.; In an effort to find novel semisynthetic macrolides with extended antibacterial spectrum and improved activity we prepared a series of compounds based on commercially available clarithromycin, a potent and safe antimicrobial agent of outstanding clinical and commercial interest . According to the literature, improvement of antibacterial activity of erythromycin type antibiotics can be achieved by introduction of fused heterocycles such as cyclic carbonates or carbamates at positions 11 and 12 (such as in telithromycin) . In the course of the work presented here, a similar, hitherto unprecedented set of compounds bearing a five-membered lactone ring fused to positions 11 and 12 was prepared based on carbon-carbon bond formation via intramolecular Michael addition of a {(hetero)arylalkylthio}acetic acid ester enolate to an alpha,beta-unsaturated ketone as the key step . Some of the ketolide compounds described in this paper were highly active against a representative set of erythromycin sensitive and erythromycin resistant test strains . The best compound showed a similar antimicrobial spectrum and comparable activity in vitro as well as in vivo as telithromycin . Furthermore, some physicochemical properties of these compounds were determined and are presented here . On the basis of these results, the novel ketolide lactones presented in this paper emerged as valuable lead compounds with comparable properties as the commercial ketolide antibacterial telithromycin (Ketek).

Genome Biol . 2004;5(6):R38 . Epub 2004 May 26.
Bacterial alpha2-macroglobulins: colonization factors acquired by horizontal gene transfer from the metazoan genome?
Budd A, Blandin S, Levashina EA, Gibson TJ.
BACKGROUND: Invasive bacteria are known to have captured and adapted eukaryotic host genes . They also readily acquire colonizing genes from other bacteria by horizontal gene transfer . Closely related species such as Helicobacter pylori and Helicobacter hepaticus, which exploit different host tissues, share almost none of their colonization genes . The protease inhibitor alpha2-macroglobulin provides a major metazoan defense against invasive bacteria, trapping attacking proteases required by parasites for successful invasion . RESULTS: Database searches with metazoan alpha2-macroglobulin sequences revealed homologous sequences in bacterial proteomes . The bacterial alpha2-macroglobulin phylogenetic distribution is patchy and violates the vertical descent model . Bacterial alpha2-macroglobulin genes are found in diverse clades, including purple bacteria (proteobacteria), fusobacteria, spirochetes, bacteroidetes, deinococcids, cyanobacteria, planctomycetes and thermotogae . Most bacterial species with bacterial alpha2-macroglobulin genes exploit higher eukaryotes (multicellular plants and animals) as hosts . Both pathogenically invasive and saprophytically colonizing species possess bacterial alpha2-macroglobulins, indicating that bacterial alpha2-macroglobulin is a colonization rather than a virulence factor . CONCLUSIONS: Metazoan alpha2-macroglobulins inhibit proteases of pathogens . The bacterial homologs may function in reverse to block host antimicrobial defenses . Alpha2-macroglobulin was probably acquired one or more times from metazoan hosts and has then spread widely through other colonizing bacterial species by more than 10 independent horizontal gene transfers . yfhM-like bacterial alpha2-macroglobulin genes are often found tightly linked with pbpC, encoding an atypical peptidoglycan transglycosylase, PBP1C, that does not function in vegetative peptidoglycan synthesis . We suggest that YfhM and PBP1C are coupled together as a periplasmic defense and repair system . Bacterial alpha2-macroglobulins might provide useful targets for enhancing vaccine efficacy in combating infections.

J Appl Microbiol, 2004, 97(1), 169 - 80
Characterization of antimicrobial peptides against a US strain of the rice pathogen Rhizoctonia solani; Oard S et al.; AIM: To identify antimicrobial peptides with high lytic activity against Rhizoctonia solani strain LR172, causal agent of rice sheath blight and aerial blight of soyabeans in the US . METHODS AND RESULTS: Among 12 natural and synthetic antimicrobial peptides tested in vitro, the wheat-seed peptide, purothionin, showed the strongest inhibitory activity that was similar to the antifungal antibiotics, nystatin and nikkomycin Z . Cecropin B, a natural peptide from cecropia moth, and synthetic peptide D4E1 produced the highest inhibitory activity against R . solani among linear peptides . Membrane permeabilization levels strongly correlated with antifungal activity of the peptides . Noticeable changes in membrane integrity were observed at concentrations of >/=0.5 micromol l(-1) for purothionin, 2 micromol l(-1) for cecropin B, D4E1, D2A21, melittin, and phor21, and 8 micromol l(-1) for magainin II and phor14 . An increase of nuclear membrane permeabilization was observed in fungal cells treated with cecropin B, but not with purothionin . Diffusion of nuclear content was observed by fluorescent microscopy 10 min after adding a lethal concentration of cecropin B . Evaluation by electron microscopy confirmed severe cytoplasmic degradation and plasma membrane vesiculation . Purothionin and cecropin B were the most stable against proteolytic degradation when added to liquid cultures of R . solani . CONCLUSIONS: Purothionin, cecropin B, D4E1 and phor21 were shown to exhibit high in vitro lytic activity against R . solani strain LR172 for rice and soyabean . These peptides are greater than 16 amino acids long and rapidly increase fungal membrane permeabilization . Resistance to proteolysis is important for sufficient antifungal activity of antimicrobial peptides . SIGNIFICANCE AND IMPACT OF THE STUDY: Selected antimicrobial peptides offer an attractive alternative to traditional chemicals that could be utilized in molecular breeding to develop crops resistant to rice sheath blight and aerial blight of soyabean.

Dermatol Ther, 2004, 17(3), 251 - 63
Hypersensitivity to preservatives; Sasseville D; Preservatives are biocidal chemicals added to cosmetics, topical medicaments, consumer goods, foods, and industrial products to protect them against microbial spoilage and to protect the consumer against infection . The ideal preservative, both effective and devoid of irritant or sensitizing potential, is still to be discovered . The present paper reviews the most important classes of preservatives, namely parabens, formaldehyde-releasers, and isothiazolinones . The author also discusses newer agents such as Euxyl K 400 and isopropynyl butylcarbamate . Each preservative is described in terms of chemical and physical characteristics, antimicrobial efficacy, exposure, cutaneous adverse reactions, patch testing concentrations, patterns of cross-reactions, and reported rates of sensitization . The history of preservatives goes back to the 1930s, and ironically, the parabens, which the industry has sought to replace with "safer" alternatives, are still the most frequently used biocides in cosmetics and appear to be far less sensitizing than most of the newer agents.

Exp Dermatol, 2004 Jun, 13(6), 340 - 6
Granulocyte colony-stimulating-factor-induced psoriasiform dermatitis resembles psoriasis with regard to abnormal cytokine expression and epidermal activation; Mossner R et al.; Psoriasis is a chronic inflammatory skin disorder characterized by accumulation of Th1-type T cells and neutrophils, regenerative keratinocyte proliferation and differentiation, and enhanced epidermal production of antimicrobial peptides . The underlying cause is unknown, but there are some similarities with the immunologic defense program against bacteria . Development of psoriasiform skin lesions has been reported after administration of granulocyte colony-stimulating factor (G-CSF), a cytokine induced in monocytes by bacterial antigens . To further investigate the relation between this type of cytokine-induced dermatitis and psoriasis, we analyzed the cutaneous cytokine profile {tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), IL-12p35 and p40, and IL-8} and expression of markers of epidermal activation {Ki-67, cytokeratin-16, major histocompatibility complex (MHC) class II, intercellular adhesion molecule-1 (ICAM-1)} in a patient who developed G-CSF-induced psoriasiform dermatitis by using quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistology . The histologic picture resembled psoriasis with regard to epidermal hyperparakeratosis and the accumulation of lymphocytes in the upper corium . CD8(+) T cells were found to infiltrate the epidermis which was associated with an aberrant expression of Ki-67, cytokeratin-16, MHC class II, and ICAM-1 on adjacent keratinocytes . As compared to normal skin (n = 7), there was an increased expression of TNF-alpha, IL-12p40, and IL-8, a decreased expression of TGF-beta1, and a lack of IL-10, similar to the findings in active psoriasis (n = 8) . Therefore, G-CSF may cause a lymphocytic dermatitis that, similar to psoriasis, is characterized by a pro-inflammatory Th1-type cytokine milieu and an epidermal phenotype indicative of aberrant maturation and acquisition of non-professional immune functions.

J Agric Food Chem, 2004 Jun 16, 52(12), 3911 - 4
Chemical composition and antimicrobial activity of the essential oils from the gum of Turkish pistachio (Pistacia vera L.); Alma MH et al.; The essential oil from the gum of Pistachio (Pistacia vera L . (Anacardiaceae)) grown in Turkey was obtained by the hydro-distillation method, and its chemical composition was analyzed by GC and GC-MS . Moreover, the antimicrobial activities of the oil against the growth of 13 bacteria and 3 pathogenic yeasts were evaluated using the agar-disk diffusion and minimum inhibitory concentration (MIC) methods . The results showed that the essential oil contained about 89.67% monoterpenes, 8.1% oxygenated monoterpenes and 1.2% diterpenes . alpha-Pinene (75.6%), beta-pinene (9.5%), trans-verbenol (3.0%), camphene (1.4%), trans-pinocarveol (about 1.20%), and limonene (1.0%) were the major components . The antimicrobial results showed that the oil inhibited nine bacteria and all the yeasts studied, and the activities were considerably dependent upon concentration and its bioactive compounds such as carvacrol, camphene, and limonene . Moreover, the essential oil of the gum was found to be more effective yeastcide than Nystatin, synthetic yeastcide . Furthermore, the antibacterial activities of the oil were lower than those of standard antibiotics, ampicillin sodium, and streptomycine sulfate under the conditions studied.

J Med Entomol, 2004 May, 41(3), 447 - 55
Ectopic expression of a cecropin transgene in the human malaria vector mosquito Anopheles gambiae (Diptera: Culicidae): effects on susceptibility to Plasmodium; Kim W et al.; Genetically altering the disease vector status of insects using recombinant DNA technologies is being considered as an alternative to eradication efforts . Manipulating the endogenous immune response of mosquitoes such as the temporal and special expression of antimicrobial peptides like cecropin may result in a refractory phenotype . Using transgenic technology a unique pattern of expression of cecropin A (cecA) in Anopheles gambiae was created such that cecA was expressed beginning 24 h after a blood meal in the posterior midgut . Two independent lines of transgenic An . gambiae were created using a piggyBac gene vector containing the An . gambiae cecA cDNA under the regulatory control of the Aedes aegypti carboxypeptidase promoter . Infection with Plasmodium berghei resulted in a 60% reduction in the number of oocysts in transgenic mosquitoes compared with nontransgenic mosquitoes . Manipulating the innate immune system of mosquitoes can negatively affect their capacity to serve as hosts for the development of disease-causing microbes.

Ital Heart J, 2004 May, 5(5), 350 - 7
Infectious agents and atherosclerosis: current perspectives and unsolved issues; Kol A et al.; The large amount of data accumulated in recent years has reinforced the idea that infectious agents may play a significant role in the pathogenesis of atherosclerosis and in the clinical manifestations of vascular disease . Seroepidemiological and experimental data linking Herpesviridae and Chlamydia pneumoniae to atherosclerosis appear to be confirmed by a number of studies, while the available evidence regarding Helicobacter pylori is more conflicting, partly due to the fact that the interest in this agent is more recent . Infectious agents may influence atherogenesis through a number of mechanisms, ranging from cell lysis to the stimulation of adhesion molecule expression and cytokine production by infected cells . The development of atherosclerosis after an acute infection seems unlikely . Rather, it appears that a chronic, persistent form of infection, especially with Chlamydia pneumoniae, may favor those structural and proinflammatory changes in the vascular wall which are necessary for the formation of an atheroma . A persistent chlamydial infection is accompanied by an increased production of microbial heat shock protein 60, which may induce antigenic mimicry and a chronic inflammatory reaction in the vascular wall . Pharmacological trials have yielded conflicting indications regarding the hypothesis that treatment with macrolide antibiotics may limit the progression of vascular disease and the recurrence of cardiovascular events, although in a limited number of cases . However, antimicrobial drugs do not act specifically against a single infectious agent and more specific therapeutic agents would be needed in order to test a causative link between a single infectious agent and vascular disease.

Rev Prat, 2003 Sep 30, 53(14), 1533 - 44
{The keys to antibiotic therapy decision making in daily practice}; Schlemmer B; Current daily good antimicrobial practice is a key point for controlling the spread of bacterial antibiotic resistance . In addition one should give every patient an optimal therapy . A pragmatic classification of antibiotics would be useful if made according to diagnosis, mainly community-acquired infections, when known to benefit from antibiotic therapy, and according to responsible bacterial species . On the basis of these bacterial species and updated knowledge of antibacterial activity of current antibiotics, a selection of several antibiotic drugs can be made for prescribers, according to their known clinical efficacy and their limitations, if any, and according to well-established therapeutic guidelines . A simple armentarium can be proposed, with the most useful and well-adapted drugs for current clinical practice of infectious diseases.

Semin Pediatr Infect Dis, 2004 Apr, 15(2), 105 - 8
Who defines resistance? The clinical and economic impact of antimicrobial susceptibility testing breakpoints; Jorgensen JH; Antimicrobial susceptibility test breakpoints are necessary for the correct clinical interpretation of quantitative or qualitative susceptibility test values of antibacterial agents . Breakpoints are selected by regulatory bodies or professional groups (eg, the National Committee for Clinical Laboratory Standards) based on an extensive review of the microbiological, pharmacokinetic, and clinical data applicable to each drug . No precise formula for selection of optimal breakpoints has been established . Instead, the process involves a review of all existing data and is influenced by the perspectives of the individuals charged with selecting the breakpoints . The interpretive breakpoints may differ somewhat by country with some antibiotics because of regional or national decisions on dosing regimens . Breakpoints also influence the selection of empiric therapy and development of local, regional, or national treatment guidelines by classifying the percentage of previously tested organisms that were susceptible to various antibiotics . Thus, antibiotic breakpoints affect the care of individual patients and provide epidemiologists and policy makers with data regarding trends in antibiotic resistance.

Semin Pediatr Infect Dis, 2004 Apr, 15(2), 99 - 104
Antimicrobial resistance: is it really that bad?
Dowell SF.
Antimicrobial resistance has been the subject of this and numerous other special issues of pediatric and infectious disease journals during the past several years . Pediatricians may be forgiven for expressing skepticism occasionally about dour scenarios predicting the advent of untreatable infections or a return to the preantibiotic era . Certainly, some benefits may accrue to pharmaceutical companies, academic and public health experts, and managed care systems from promoting concern about antimicrobial resistance . In fact, the response to the spread of resistance has been forceful, and in some cases successful, with reductions achieved in unnecessary prescribing, treatment regimens modified, and some new antimicrobial agents made available during the past several years . The problem, however, remains substantial, as several clear examples of dangerous and nearly untreatable multiply resistant organisms exist and the costs associated with treating resistant organisms continue to skyrocket . In many instances in the developing world, antimicrobial resistance can mean that a formerly treatable infection has become untreatable, and for pediatricians in the United States, resistance has, at the least, complicated therapy and limited options in everyday practice.

Semin Pediatr Infect Dis, 2004 Apr, 15(2), 94 - 8
Antimicrobial resistance in countries with limited resources: unique challenges and limited alternatives; Sirinavin S et al.; The haphazard use of antimicrobial agents has caused these essential drugs to lose their effectiveness . In the resource-poor parts of the world, the problem is complex, involving inadequate access to antimicrobial agents in the poorest countries along with an excessive variety of drugs in middle-income countries that have inadequate capability to use them well or to control the unnecessary emergence of resistant microbes . Both circumstances may result in the rapid dissemination of antimicrobial resistance . Resistant organisms, which in wealthy countries would result in the increased expense or inconvenience of alternative agents, in poor countries may cause infections that for practical purposes are untreatable . The basic requirements for controlling drug-resistant problems in resource-poor and wealthy countries alike include first-line prevention of infectious diseases, laboratory support for etiologic diagnosis, adequate surveillance and epidemiological information, appropriate drug selection, locally appropriate guidelines for treatment, and proper education about infectious diseases in all levels . These requirements generally are lacking in resource-poor countries . The most important key to success in these countries is a strong central commitment and governmental support for minimizing drug-resistance problems while maintaining the highest effectiveness of health care within the limits of available resources.

Semin Pediatr Infect Dis, 2004 Apr, 15(2), 86 - 93
Vaccines as tools against resistance: the example of pneumococcal conjugate vaccine; Whitney CG et al.; Pneumococcal conjugate vaccine not only reduces the incidence of invasive antibiotic-resistant pneumococcal infections in young children receiving the vaccine, but it also reduces transmission of these strains to their younger siblings and to adults . Evidence from the United States indicates that the burden of resistant pneumococcal invasive disease in adults is reduced by immunization of children with these vaccines . Data from Israel and California suggest that antibiotic use is reduced in immunized children, and this reduction in use may further reduce the selection of antibiotic-resistant strains in immunized communities . Surveillance is needed to monitor the spread of antimicrobial resistance into nonvaccine serotypes, which may lead to a resurgence of resistance.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2004 Jun, 97(6), 718 - 25
Oral mucosal pigmentation secondary to minocycline therapy: report of two cases and a review of the literature; Treister NS et al.; Minocycline is a semisynthetic broad-spectrum antimicrobial agent that was first introduced into clinical practice in 1967 . The most common use of minocycline is for the long-term treatment of acne vulgaris . A well-recognized side effect of minocycline treatment is pigmentation, which has been reported in multiple tissues and fluids including thyroid, skin, nail beds, sclera, bone, and teeth . While there have been several reports of oral pigmentation following minocycline therapy, these have been, for the most part, pigmentation of the underlying bone with the overlying oral mucosa only appearing pigmented . We report two cases of actual pigmented oral mucosal lesions on the hard palate secondary to minocycline therapy with the accompanying histopathology, followed by a discussion of minocycline-induced oral pigmentation and a differential diagnosis of these lesions .

J Med Microbiol, 2004 Jul, 53(Pt 7), 639 - 44
Do procalcitonin and C-reactive protein levels have a place in the diagnosis and follow-up of Helicobacter pylori infections?
Saribas S, Kocazeybek B, Aslan M, Altun S, Seyhun Y, Oner YA, Memisoglu N.
The aims of this study were to determine the levels of procalcitonin (PCT) and C-reactive protein (CRP) in Helicobacter pylori-positive (HP+) patients diagnosed with duodenal and gastric ulcer and to evaluate the correlation of PCT and CRP levels with other invasive and non-invasive diagnostic methods for determination of H . pylori eradication in post-treatment follow-up . Thirty-five HP+ patients with dyspepsia were included in this study . Serum samples (5 ml) were collected at admission and after 24 h . Antimicrobial therapy (omeprazole, amoxycillin and clarithromycin) was given for 1 week to HP+ patients who were positive only by culture or by urease test plus pathology . After 1 month, serum samples (5 ml) were collected again and culture, urease and pathology investigations were performed on endoscopic samples . PCT and CRP levels were measured in the collected blood samples . Thirty-five H . pylori-negative (HP-) cases with dyspepsia, 38 cases with bacteraemia and 35 healthy blood donors were included in this study as control groups . The mean and minimum-maximum levels of PCT were 1.39 (0.25-6.75), 0.35 (0.12-0.71), 7.45 (0.68-51.5) and 0.40 (0.12-0.71) ng ml(-1) for the groups of HP+, HP- and bacteraemia patients and healthy donors, respectively . Mean CRP levels were 1.00 (<0.5-8.11), 0.62 (<0.5-3.2), 11.5 (3.2-43.5) and 0.63 (<0.5-5.46) mg dl(-1) for the same groups . A statistically significant difference was found between HP+ patients and both HP- cases and healthy blood donors for PCT levels, and higher PCT levels were found on admission in cases of bacteraemia than in the other groups (P < 0.05) . PCT levels of HP+ cases decreased significantly (from 1.39 to 0.86) between admission and the post-treatment period (30 days); however, PCT levels remained higher than the cut-off value (0.5 ng ml(-1)) . Similar ranges of CRP levels were found over the same time-period . The sensitivity of PCT was found to be higher than that of CRP on admission, but the specificity of PCT was found to be lower than that of CRP on the day of admission (65 and 74%, respectively) . The sensitivity of PCT was the same as that of CRP for the post-treatment period, but specificity of PCT was higher than that of CRP for the post-treatment period (83 and 76%, respectively) . It was concluded that PCT and CRP are not very effective markers for H . pylori infection in primary diagnosis or in eradication follow-up after therapy when used in parallel with conventional diagnostic methods, even if there is a difference in PCT and CRP levels between HP+ and HP- cases on admission.

J Clin Microbiol, 2004 Jun, 42(6), 2858 - 60
Hernia repair mesh-associated Mycobacterium goodii infection; Sohail MR et al.; We report on a patient with an abdominal wall abscess that developed after an inguinal hernia repair that utilized synthetic mesh . Mycobacterium goodii, a recently recognized, rapidly growing mycobacterium related to M . smegmatis, was isolated both from the abdominal wall aspirate and from surgically drained material . Infection resolved following thorough debridement, mesh removal, and prolonged antimicrobial therapy . This case report extends our understanding of the spectrum of M . goodii infection.

Phytochemistry, 2004 May, 65(9), 1291 - 8
Antibacterial diterpenes and their fatty acid conjugates from rice leaves; Kono Y et al.; Six structurally oryzalide-related compounds, oryzadione (1), 2, 3, 4, 5 and 6, were isolated from a neutral fraction of the extract of healthy leaves using a bacterial leaf blight-resistant cultivar of a rice plant, "Norin-27", as a group of antimicrobial substances . Their structures were determined by spectroscopic studies to be kaurane analogues and kaurane analogues conjugated with fatty acids, i.e., 1: ent-15,16-epoxy-kauran-2,3-dione (enol form: ent-15,16-epoxy-2-hydroxy-kauran-1-en-3-one), 2: ent-15,16-epoxy-3beta-hydroxy-kauran-2-one, 3: ent-15,16-epoxy-3-oxa-kauran-2-one, 4: ent-15,16-epoxy-3beta-myristoyloxy-kauran-2-one, 5: ent-15,16-epoxy-3alpha-palmitoyloxy-kauran-2-one, and 6: ent-15,16-epoxy-2beta-palmitoyloxy-kauran-2-one.

Phytochemistry, 2004 May, 65(9), 1255 - 64
Essential oils from New Zealand manuka: triketone and other chemotypes of Leptospermum scoparium; Douglas MH et al.; The triketone chemotype of manuka, Leptospermum scoparium (Myrtaceae), is commercially important because of its antimicrobial activity . Oils from 36 individual plants on the East Cape of New Zealand all showed similar high triketone contents (>20% total triketones) with little seasonal variation . Analyses of oils from 261 individual manuka plants collected from 87 sites throughout New Zealand showed that the high triketone chemotype was localised on the East Cape, although oils with triketone levels up to 20% were found in the Marlborough Sounds area of the South Island . Cluster analysis revealed other chemotypes localised on other areas . Ten further chemotypes are described: alpha-pinene; sesquiterpene-rich with high myrcene; sesquiterpene-rich with elevated caryophyllene and humulene; sesquiterpene-rich with an unidentified sesquiterpene hydrocarbon; high geranyl acetate; sesquiterpene-rich with high gamma-ylangene + alpha-copaene and elevated triketones; sesquiterpene-rich with no distinctive components; sesquiterpene-rich with high trans-methyl cinnamate; high linalol; and sesquiterpene-rich with elevated elemene and selinene . Some of the chemotypes contained aroma compounds at relatively high levels, with a geranyl acetate-rich oil being most notable . Possible origins for this complex array of chemotypes are proposed.

FEMS Microbiol Lett, 2004 Jun 15, 235(2), 305 - 9
Low level of cross-resistance between triclosan and antibiotics in Escherichia coli K-12 and E . coli O55 compared to E . coli O157; Braoudaki M et al.; Misuse of biocides has encouraged the emergence of resistance and cross-resistance in certain strains . This study investigated resistance of triclosan-adapted Escherichia coli K-12 and E . coli O55 to antimicrobial agents and compared these to E . coli O157:H7 . Cross-resistance in E . coli K-12 and E . coli O55 was observed however to a lesser extent than in E . coli O157:H7 . Triclosan-adapted E . coli K-12 demonstrated cross-resistance to chloramphenicol, whereas triclosan-adapted E . coli O55 exhibited resistance to trimethoprim . In comparison, E . coli O157:H7 was resistant to chloramphenicol, tetracycline, amoxicillin, amoxicillin/clavulanic acid, trimethoprim, benzalkonium chloride and chlorohexidine suggesting strain specific rather than general resistance mechanisms.

Diagn Microbiol Infect Dis, 2004 Jun, 49(2), 141 - 5
Are United States hospitals following national guidelines for the analysis and presentation of cumulative antimicrobial susceptibility data?
Ernst EJ, Diekema DJ, BootsMiller BJ, Vaughn T, Yankey JW, Flach SD, Ward MM, Franciscus CL, Acosta E, Pfaller MA, Doebbeling BN.
The National Committee for Clinical Laboratory Standards recently published guidelines for analysis and presentation of cumulative antimicrobial susceptibility test data (antibiograms) . We sought to determine how well US hospitals already adhere to standards for antibiogram compilation, and to examine the relationship between hospital characteristics and guideline adherence . We surveyed laboratory directors at 670 hospitals and examined 3 guideline criteria: compilation of an antibiogram, annual updating, and distribution to infection control staff and medical staff yearly; 494 surveys were returned (74%) . Almost all of the hospitals surveyed publish an antibiogram (95%, n = 481); however, only 60% (n = 296) met all three criteria . Hospital laboratories meeting criteria were more likely to serve as referral laboratories (OR = 1.82; 95% CI = 1.26-2.63), perform susceptibility testing on site (OR = 4.47; 95% CI = 1.84-10.84), use confirmatory tests to detect extended-spectrum beta-lactamases (OR = 1.8; 95% CI = 1.2-2.6), and have more laboratory personnel per bed (3.0 vs . 2.0 FTEs/bed, p = 0.0031) . Adherence to guidelines for preparation and dissemination of antibiograms could be improved . Institutional commitment to high quality, on-site microbiology laboratory services will improve adherence to these guidelines .

Diagn Microbiol Infect Dis, 2004 Jun, 49(2), 131 - 9
How does susceptibility prevalence impact on the performance of disk diffusion susceptibility testing?
Lamy B, Carret G, Flandrois JP, Delignette-Muller ML.
Antimicrobial disk diffusion susceptibility testing, devoted in a clinical context to predicting whether an antibiotic regimen will be effective, should be evaluated through predictive values . This approach implies that the susceptibility prevalence (frequency of susceptible, intermediate, and resistant isolates) affects the predictive value of a result . We quantified the influence of the susceptibility prevalence variation on the disk diffusion method performance through a modeling approach . Simulations based on a resampling procedure from two distinct minimum inhibitory concentration/diameter data sets were performed . Experimental variability on minimum inhibitory concentration and diameters was taken into account in the simulations . Results show that the susceptibility prevalence impact depends on the antibiotic and may be significant when prevalence variation is high enough . Consequences of these results on zone diameter breakpoint determination policy are discussed . This implies that the following should be done: (i) consider more rigorously the susceptibility prevalence in studies dealing with zone diameter breakpoint determination and performance evaluation, (ii) re-evaluate disk diffusion breakpoint consistency when the weight of prevalence variation is noteworthy, (iii) estimate consequences of a breakpoint international consensus on prediction quality and appropriate patient management .

Diagn Microbiol Infect Dis, 2004 Jun, 49(2), 105 - 8
Review of the pharmacodynamics of antibiotic use in animal food production; Florea NF et al.; Much attention has been focused on food-producing animals as a potential source of antimicrobial-resistant bacteria in humans . These efforts, however, have been met with continued debate and disagreement within the medical, veterinary, and regulatory communities as to whether the veterinary use of antimicrobials is a significant risk factor for the development of antimicrobial-resistant pathogens . As such, it is the purpose of our paper to assess factors involved in the pharmacokinetics and pharmacodynamics of antibiotic use in animal food production . We conclude that, based on the number of variables involved and the lack of definitive studies, it is difficult to determine the AUC:MIC for antimicrobials . Unfortunately, we are left only with general principles that indicate that low doses of antibiotic tend to select for bacterial resistance, and high doses tend to kill the microorganism . In the case where animal-associated pathogens cause human disease, those practices that target adequate exposures (AUC:MIC) of antimicrobials should continue, whereas those practices producing low exposures should be modified or halted to prevent the emergence and spread of resistant organisms .

Diagn Microbiol Infect Dis, 2004 Jun, 49(2), 77 - 82
Endotipsitis: an emerging prosthetic-related infection in patients with portal hypertension; Bouza E et al.; The transjugular intrahepatic portosystemic shunt (TIPS) is an option for the treatment of portal hypertension . However, TIPS infection (endotipsitis) is distinctly uncommon . We report 3 new patients and review 23 published cases of endotipsitis . We calculate an incidence of 1.33% in patients undergoing the procedure . Twenty-three cases (88%) occurred more than a month after the procedure . The most common presentation included fever and primary bacteremia or fungemia . Gram-positive (18 cases), gram-negative microorganisms (10 cases), and fungi (3 cases) were the etiologic agents . Diagnosis may be difficult to establish, and new diagnostic criteria have been proposed . Twenty patients responded well to antibiotic treatment, and the 6 remaining patients died because of the infection . Endotipsitis is a new infectious disease to be considered in patients with a TIPS and bloodstream infection that is not clearly attributable to another source . Prolonged courses of antimicrobial agents can be curative, but liver transplantation is also an option to consider .

Int J Radiat Oncol Biol Phys, 2004 Jul 1, 59(3), 809 - 14
Silver leaf nylon dressing to prevent radiation dermatitis in patients undergoing chemotherapy and external beam radiotherapy to the perineum; Vuong T et al.; PURPOSE: Silver-leaf nylon dressing (SLND) has been shown to have effective antimicrobial activity and to enhance healing in burns and skin grafts . The purpose of this study was to evaluate the value of SLND in preventing radiation dermatitis in patients undergoing radiotherapy to target volumes that included the perineum and concurrent chemotherapy . METHODS AND MATERIALS: Fifteen consecutive patients with either anal canal or gynecologic cancer were offered the SLND as a preventive intervention . The evaluation was based on standardized photographs taken at the end of treatment . A historical control group of 15 patients with the same neoplasms who received standard skin care was assessed in the same fashion . Ten observers unaware of the treatment intervention were enrolled in the evaluation of the skin changes . The Mann-Whitney U test was used to assess the statistical significance of the differences in the dermatitis scores between the two patient groups . RESULTS: The mean dermatitis score for controls was 2.62 (standard deviation, 0.48) . The mean score for the SLND group was significantly lower at 1.16 (standard deviation, 0.40; p <0.0001) . CONCLUSION: The results of this study suggest that SLND is effective in reducing radiation dermatitis, apparently because of its antibacterial properties.

Cutis, 2004 May, 73(5 Suppl), 30 - 2
Compliance with antibiotics; O'Donoghue MN; Several factors influence the clinician's choice of antimicrobial therapy . While efficacy and toxicity can be important discriminators in the treatment of skin and soft tissue infections, patient compliance with antibiotic medication is a key component to successful therapy . The general parameters affecting compliance are discussed herein, and antibiotic-specific factors affecting compliance are discussed briefly.

SADJ, 2004 Mar, 59(2), 65 - 6, 69-71, 73-4
Salivary glands: applied anatomy and clinical correlates; du Toit DF et al.; The major salivary glands include the paired parotid, submandibular and sublingual glands . Salivary glands act as accessory digestive glands and produce a secretion referred to as saliva . Saliva has lubricating, cleansing, digestive and antimicrobial properties . The parotid is the largest salivary gland and saliva is secreted into the mouth via the parotid duct (Stensen's duct) . The submandibular gland lies inferior to the body of the mandible and is susceptible to sialolithiases . Drainage is via the duct of the submandibular gland (Wharton's duct) into the floor of the mouth on either side of the lingual frenulum . The sublingual glands are situated under the mucosa in the floor of the mouth, on the sides of the tongue . These glands are in relationship to important nerves in the surrounding tissue . Disease processes such as chronic intraparenchymal sialolithiasis and neoplastic changes frequently mandate surgical removal of the underlying salivary gland . Detailed, applied knowledge of anatomy on a regional basis is required to avoid inadvertent nerve damage during surgery and resulting litigation.

Med Princ Pract, 2004 Jul-Aug, 13(4), 215 - 9
Seroepidemiological and microbiological study of brucellosis in Kuwait; Dimitrov Ts et al.; OBJECTIVE: The primary objective of the study was to determine the prevalence of brucellosis and the antimicrobial susceptibility pattern of local Brucellae isolates in the Infectious Diseases Hospital, Kuwait . SUBJECTS AND METHODS: A single serum sample was collected from each of 1,836 patients of different nationalities from January 2000 to December 2001 . Any patient with a provisional diagnosis of fever or brucellosis had a standard tube agglutination (STA) test for the quantitation of Brucella antibodies . Blood cultures were done in 166 of 455 patients with significant STA titers, using the Bactec system . Antimicrobial susceptibility testing of 123 isolates of Brucella spp . was done against 8 antimicrobial agents . RESULTS: A total of 455 serum samples (24.8%) having an STA titer of > or =1:160 were presumptively diagnosed as cases of brucellosis . The peak isolation was in April and May . Brucella spp . were isolated from 123 blood cultures (74.1%) . The blood culture isolation rate was significantly higher in patients with an STA titer of >/=1:1,280 than in those with an STA titer of </=1:160 (p < 0.05) . Antimicrobial susceptibility testing showed good in vitro activity of tetracycline, gentamicin, amikacin, streptomycin and ciprofloxacin against all isolates . Azithromycin had good anti-Brucella activity against only 42% of the isolates, while rifampicin and trimethoprim-sulfamethoxazole showed low in vitro anti-Brucella activity against 8 and 25% of the isolates, respectively . CONCLUSION: Brucellosis is quite common in Kuwait . Kuwaiti and Bangladeshi nationals were most affected . Significant titers on the STA test were detected in 24.8% of serum samples . Good in vitro activity against all isolates was found with tetracycline, gentamicin, amikacin, ciprofloxacin and streptomycin, and low activity with azithromycin, rifampicin and trimethoprim-sulfamethoxazole .

Curr Med Chem, 2004 Jun, 11(11), 1451 - 60
Antimicrobial and chemopreventive properties of herbs and spices; Lai PK et al.; Herbs and spices have been used for generations by humans as food and to treat ailments . Scientific evidence is accumulating that many of these herbs and spices do have medicinal properties that alleviate symptoms or prevent disease . A growing body of research has demonstrated that the commonly used herbs and spices such as garlic, black cumin, cloves, cinnamon, thyme, allspices, bay leaves, mustard, and rosemary, possess antimicrobial properties that, in some cases, can be used therapeutically . Other spices, such as saffron, a food colorant; turmeric, a yellow colored spice; tea, either green or black, and flaxseed do contain potent phytochemicals, including carotenoids, curcumins, catechins, lignan respectively, which provide significant protection against cancer . This review discusses recent data on the antimicrobial and chemopreventive activities of some herbs and spices and their ingredients.

Curr Med Chem, 2004 Jun, 11(11), 1423 - 30
Immunomodulatory and antimicrobial effects of some traditional chinese medicinal herbs: a review; Tan BK et al.; The current practice of ingesting phytochemicals to support the immune system or to fight infections is based on centuries-old tradition . We review reports on seven Chinese herbs, (Aloe vera Mill . (Aloaceae), Angelica species (Umbelliferae), Astragalus membranaceus Bunge . (Leguminosae), Ganoderma lucidum (Fr.) Karst . (Ganodermataceae), Panax ginseng C.A Mey . (Araliaceae), Scutellaria species (Lamiaceae) and Zingiber officinale Rosc . (Zingiberaceae) with emphasis to their immunomodulatory and antimicrobial activities . While some of these herbaceous plants have a direct inhibitory effect on microbial organisms, we observe that each plant has at least one compound that selectively modulates cells of the immune system . The successful derivation of pure bioactive compounds from Ganoderma lucidum, ginseng and Zingiber officinale supports the traditional practice of using these plants to stimulate the immune system . As many modern drugs are often patterned after phytochemicals, studying the influence of each compound on immune cells as well as microbes can provide useful insights to the development of potentially useful new pharmacological agents.

Curr Med Chem, 2004 Jun, 11(12), 1657 - 69
Organoselenium compounds as potential therapeutic and chemopreventive agents: a review; Soriano-Garcia M; Selenium is an essential trace element . It is, however toxic at concentration little above which is required for health . Selenium is incorporated into proteins as selenocysteine, the 21(st) amino acid . Selenoproteins are found in bacteria, archaea and eukaryotes . Biochemical and physicochemical properties of selenium result in the unique redox characteristics of selenocysteine and its use in antioxidant enzymes . In this context of a redox reaction is the reduction of reactive oxygen metabolites by glutathione peroxidases, helping to maintain membrane integrity, reduces the oxidative damage to lipids, lipoproteins, and DNA . Selenium has structural and enzymatic roles . Selenium influences a number of endocrine processes, most notably, those involved in thyroid hormone synthesis and metabolism . Se is needed for the proper functioning of the immune system, a role in viral suppression, AIDS, and also is implicated in delaying the aging process . Its deficiency has been linked to a number of disorders such as heart disease, diabetes, and diseases of the liver, and it is required for sperm motility and may reduce the risk of miscarriage . Se supplementation has recently moved from the realm of correcting nutritional deficiencies to one of pharmacological intervention, especially in the clinical domain of cancer chemoprevention . During the last few years, a tremendous effort has been directed toward the synthesis of stable organoselenium compounds that could be used as antioxidants, enzyme modulators, antitumor, antimicrobials, antihypertensive agents, antivirals and cytokine inducers . The biochemistry and pharmacology of selenium-based compounds are subjects of intense current interest, especially from the point of view of public heath . The purpose of this review is to discuss the recent pharmacological applications of organoselenium compounds as therapeutic agents in the treatment of several diseases.

Drug News Perspect, 2004 Apr, 17(3), 219 - 24
The history of bacterial meningitis treatment; Borchardt JK; Few diseases have been affected more by the advent of antimicrobial therapy than bacterial meningitis . From its recognition in 1805 to the early 20th century, bacterial meningitis was deadly . The 1940s brought the advent of effective drug therapy . Bacterial meningitis remains common today with growing drug resistance to the disease organisms complicating antibiotic therapy . (c) 2004 Prous Science . All rights reserved.

Shock, 2004 Apr, 21(4), 329 - 35
Development and characterization of a novel porcine model of neonatal sepsis; Kato T et al.; Sepsis and its sequela remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care . Many models of neonatal sepsis have been developed for investigating the pathophysiology of this disease and application of therapy, and a model with an infectious focus is closer to clinical reality . To establish an animal model that mimics the clinical characteristics of neonatal sepsis, the cecal devascularization and perforation procedure was implemented on 15 mixed-strain newborn piglets, which produced an infectious focus that acted as a continuous source of microorganisms to the peritoneal cavity . The mean survival time in animals with sepsis was 10.4 h (range 5.5-17.9 h), whereas all of the sham-operated control animals survived more than 24 h . Animals with sepsis showed a gradual significant decrease in the mean systemic blood pressure (mSBP; 71 +/- 3 mmHg in sepsis vs . 64 +/- 3 mmHg in control at 3 h, 38 +/- 7 mmHg in sepsis vs . 59 +/- 4 mmHg in control at 6 h, mean +/- SEM) . They also showed an increase of serum levels of endotoxin (5.6 x 10 +/- 4.5 x 10 pg/mL in sepsis vs . 6.0 x 10 +/- 3.8 x 10 pg/mL in control at 6 h) . Serum levels of TNF-alpha in the animals with sepsis became significantly higher than the control animals at 0 h (96 +/- 31 pg/mL in sepsis vs . 12 +/- 1 pg/mL in control) and remained significantly higher than all through the experiment . Serum levels of IL-6 in animals with sepsis showed a gradual increase (484 +/- 231 pg/mL in sepsis in its peak at 6 h vs . 24 +/- 5 pg/mL in control), however, there were no significant differences in serum IL-10 levels between the groups . Microorganisms detected in the blood of animals with sepsis were gram-negative enteric and anaerobic organisms . These results suggested that this model mimics the clinical state of neonatal sepsis and hence may have significant implications for the treatment of sepsis, including its use as a model in further investigations.

Mol Cells, 2004 Apr 30, 17(2), 274 - 80
Cloning and expression of the glucose-1-phosphate thymidylyltransferase gene (gerD) from Streptomyces sp . GERI-155; Lee HC et al.; GERI-155 is a macrolide antibiotic containing two deoxyhexose molecules, that has antimicrobial activity against Gram-positive bacteria . The deoxysugar biosynthetic gene cluster of GERI-155 was cloned from Streptomyces sp., GERI-155 . One of the orfs, gerD, appeared to encode glucose-1-phosphate thymidylyltransferase (dTDP-glucose synthase), which converts dTTP and glucose-1-phosphate to dTDP-D-glucose and pyrophosphate . GerD was expressed in E . coli in vector pHJ2 and the expressed protein was purified to apparent homogeneity by ammonium sulfate precipitation and DEAE-Sepharose CL-6B and DEAE-Trisacryl column chromatography . The specific activity of the enzyme increased 16-fold with a recovery of 10% . It migrated as a single band on SDS-PAGE with a molecular mass of 30 kDa . The purified protein had glucose-1-phosphate thymidylyltransferase activity, catalyzing a reversible bimolecular group transfer reaction . In the forward reaction the highest activity was obtained with the combination of dTTP and alpha-D-glucose-1-phosphate, and only 5.5% of that activity was obtained with UTP in place of dTTP . In the opposite direction the purified protein was highly specific for dTDP-D-glucose and pyrophosphate.

Mol Cells, 2004 Apr 30, 17(2), 262 - 6
Purification and cDNA cloning of a cecropin-like peptide from the great wax moth, Galleria mellonella; Kim CH et al.; A cecropin-like antimicrobial peptide, Gm cecropin, was purified from hemolymph of larvae of the wax moth, Galleria mellonella, immunized against E . coli, and its antibacterial activity was examined in a radial diffusion assay . The molecular mass of Gm cecropin was 4,160.69 Da by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis . The full-length cDNA of the Gm cecropin precursor was cloned by a combination of RT-PCR, based on the N-terminal sequence obtained by Edman degradation, and 5'-RACE-PCR . Analysis of the cDNA showed that cecropin is synthesized as a prepropeptide, with a putative 22-residue signal peptide, a 4-residue propeptide and a 39-residue mature peptide with a calculated mass of 4,344.18 Da the difference between the calculated and measured masses suggests that Gm cecropin is a 37-residue peptide generated by removal of the C-terminal residue and amidation.

J Leukoc Biol, 2004 Sep, 76(3), 701 - 8 Epub 2004 Jun 03.
I-TAC/CXCL11 is a natural antagonist for CCR5; Petkovic V et al.; The selective CXC chemokine receptor 3 (CXCR3) agonists, monokine induced by interferon-gamma (IFN- gamma)/CXC chemokine ligand 9 (CXCL9), IFN-inducible protein 10/CXCL10, and IFN-inducible T cell alpha chemoattractant (I-TAC)/CXCL11, attract CXCR3+ cells such as CD45RO+ T lymphocytes, B cells, and natural killer cells . Further, all three chemokines are potent, natural antagonists for chemokine receptor 3 (CCR3) and feature defensin-like, antimicrobial activities . In this study, we show that I-TAC, in addition to these effects, acts as an antagonist for CCR5 . I-TAC inhibited the binding of macrophage-inflammatory protein-1alpha (MIP-1alpha)/CC chemokine ligand 3 (CCL3) to cells transfected with CCR5 and to monocytes . Furthermore, cell migration evoked by regulated on activation, normal T expressed and secreted (RANTES)/CCL5 and MIP-1beta/CCL4, the selective agonist of CCR5, was inhibited in transfected cells and monocytes, respectively . In two other functional assays, namely the release of free intracellular calcium and actin polymerization, I-TAC reduced CCR5 activities to minimal levels . Sequence and structure analyses indicate a potential role for K17, K49, and Q51 of I-TAC in CCR5 binding . Our results expand on the potential role of I-TAC as a negative modulator in leukocyte migration and activation, as I-TAC would specifically counteract the responses mediated by many "classical," inflammatory chemokines that act not only via CCR3 but via CCR5 as well.

Farmaco, 2004 Jun, 59(6), 463 - 71
New 6-nitroquinolones: synthesis and antimicrobial activities; Sbardella G et al.; Pursuing our searches on quinolonecarboxylic acids we used a simple three-step one pot procedure to synthesize novel 1,7-disubstituted-6-nitroquinolones . The new derivatives were tested against Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) as well as against both gram-positive and gram-negative bacteria . In vitro assays showed some derivatives were endowed with good inhibiting activities against tested mycobacteria . Some derivatives were also found more potent than ciprofloxacin and ofloxacin (used as reference drugs) against gram-positive bacteria.

Farmaco, 2004 Jun, 59(6), 443 - 50
Synthesis and in vitro antifungal activity of 4-substituted phenylguanidinium salts; Braunerova G et al.; A series of 4-substituted phenylguanidinium derivatives was synthesized and its antimicrobial activity was evaluated in vitro against eight potentially pathogenic strains of fungi.

Clin Lab Med, 2004 Jun, 24(2), 477 - 502
Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of respiratory tract infections; Andes D et al.; The pharmacologic field that studies antimicrobial pharmacokinetics and pharmacodynamics (PK/PD) has had a major impact on the choice and dosing regimens used for many antibiotics especially those used in the treatment of respiratory tract infections . PK/PD parameters are particularly important in light of increasing antimicrobial resistance . Drug pharmacokinetic features, such as serum concentrations over time and area under the concentration-time curve, when integrated with minimum inhibitory concentration (MIC) values of antibiotics against pathogens, can predict the probability of bacterial eradication and clinical success . These pharmacokinetic and pharmacodynamic relationships also are important in preventing the selection and spread of resistant strains and have led to the description of the mutation prevention concentration, which is the lowest concentration of antimicrobial that prevents selection of resistant bacteria from high bacterial inocula . b-lactams are time-dependent agents without significant post-antibiotic effects, resulting in bacterial eradication when unbound serum concentrations exceed MICs of these agents against infecting pathogens for >40% to 50% of the dosing interval . Macrolides, azaolides, and lincosamides are time-dependent agents with prolonged post-antibiotic effects, and fluoroquinolones are concentration-dependent agents, resulting in both cases in bacterial eradication when unbound serum area-under-the-curve to MIC ratios exceed 25 to 30 . These observations have led to changes in recommended antimicrobial dosing against respiratory pathogens and are used to assess the role of current agents, develop new formulations, and assess potency of new antimicrobials.

Clin Lab Med, 2004 Jun, 24(2), 419 - 53
Mechanisms of resistance among respiratory tract pathogens; Jacobs MR et al.; Antimicrobial resistance among respiratory tract pathogens represents a significant health care threat . Identifying the antimicrobial agents that remain effective in the presence of resistance, and knowing why, requires a thorough understanding of the mechanisms of action of the various agents as well as the mechanisms of resistance demonstrated among respiratory tract pathogens . The primary goal of antimicrobial therapy is to eradicate the pathogen, via killing or inhibiting bacteria, from the site of infection; the defenses of the body are required for killing any remaining bacteria . Targeting a cellular process or function specific to bacteria and not to the host limits the toxicity to patients . Currently, there are four general cellular targets to which antimicrobials are targeted: cell wall formation and maintenance, protein synthesis, DNA replication, and folic acid metabolism . Resistance mechanisms among respiratory tract pathogens have been demonstrated for all four targets . In general, the mechanisms of resistance used by these pathogens fall into one of three categories: enzymatic inactivation of the antimicrobial, prevention of intracellular accumulation, and modification of the target site to which agents bind to exert an antimicrobial effect . Resistance to some agents can be overcome by modifying the dosage regimens (e.g., using high-dose therapy) or inhibiting the resistance mechanism (e.g., b-lactamase inhibitors), whereas other mechanisms of resistance can only be overcome by using an agent from a different class . Understanding the mechanisms of action of the various agents and the mechanisms of resistance used by respiratory tract pathogens can help clinicians identify the agents that will increase the likelihood of achieving optimal outcomes.

Semin Pediatr Infect Dis, 2004 Jan, 15(1), 30 - 40
Controlling healthcare-associated infections: the role of infection control and antimicrobial use practices; Jarvis WR; Healthcare-associated infections are a major cause of morbidity and mortality in pediatric patients in the United States and throughout the world . Overall rates of infection range widely depending on the pediatric population, with the highest rates being in patients in neonatal intensive care units, followed by those in pediatric intensive care units, immunocompromised patients, and those undergoing surgical procedures . Risk factors for healthcare-associated infection include intrinsic and extrinsic factors . The major intrinsic factors are age, birth weight, underlying diseases, and immune status . The major extrinsic factors are presence of invasive devices and procedures . The major risk factors for healthcare-associated infection caused by antimicrobial-resistant pathogens are either the transmission of pathogens from person to person (directly or indirectly, usually via the hands of healthcare workers) or the emergence of resistance after exposure to antimicrobials . Preventing healthcare-associated infections caused by antimicrobial-resistant pathogens requires a comprehensive approach that includes: 1) preventing infections through the use of vaccines and prophylaxis; 2) minimizing the use of invasive devices; 3) understanding and fully implementing (and complying with) current guideline recommendations for the prevention of infections; and 4) using antimicrobials judiciously . Implementing such a comprehensive program will reduce healthcare-associated infections, reduce the prevalence of antimicrobial-resistant pathogens, improve patient outcomes, and reduce health care costs.

Am J Infect Control, 2004 Jun, 32(4), 239 - 42
Clinical nurse specialists and nurse practitioners: complementary roles for infectious disease and infection control; Gail C et al.; BACKGROUND: The escalation of infectious diseases worldwide heralds an unprecedented need for nurses with advanced practice graduate preparation . OBJECTIVE: To describe how a graduate program prepares clinical nurse specialists and nurse practitioners in infectious diseases or infection control to provide distinct yet complementary care for patients with contagious disease and potentially antimicrobial-resistant infections . RESULTS: The University of Washington School of Nursing launched a new master of nursing program for infectious disease and infection control to reduce the threat of infectious diseases and multiple-resistant organisms.

J Nucl Med Technol, 2004 Jun, 32(2), 47 - 57; quiz 58-9
Radionuclide imaging of infection; Love C et al.; Although our understanding of microorganisms has advanced significantly and antimicrobial therapy has become increasingly available, infection remains a major cause of patient morbidity and mortality . The role of radionuclide imaging in the evaluation of the patient suspected of harboring an infection varies with the situation . For example, in the postoperative patient, radionuclide imaging is complementary to CT and is used to help differentiate postoperative changes from infection . In the case of the painful joint replacement, in contrast, radionuclide studies are the primary diagnostic imaging modality for differentiating infection from other causes of prosthetic failure . Several tracers are available for imaging infection: (99m)Tc-diphosphonates, (67)Ga-citrate, and (111)In- and (99m)Tc-labeled leukocytes . At the moment, in immunocompetent patients, labeled leukocyte imaging is the radionuclide procedure of choice for detecting most infections . There are, unfortunately, significant limitations to the use of labeled leukocytes . The in vitro labeling process is labor intensive, is not always available, and involves direct handling of blood products . For musculoskeletal infection, the need to frequently perform complementary marrow or bone imaging adds complexity and expense to the procedure and is an inconvenience to patients . Considerable effort has therefore been devoted to the search for alternatives to this procedure, including in vivo methods of labeling leukocytes, (18)F-FDG PET, and radiolabeled antibiotics . This article reviews the current status of nuclear medicine infection imaging and the potential of a murine monoclonal antigranulocyte antibody, fanolesomab, that is currently under investigation . Upon completion of this article, the reader will be familiar with the physical characteristics and uptake mechanisms of tracers currently approved for infection imaging, the indications for the uses of these tracers, and the characteristics and potential indications for a murine monoclonal antigranulocyte antibody under investigation.

Ann Intern Med, 2004 Jun 1, 140(11), 910 - 22
Systematic review: surveillance systems for early detection of bioterrorism-related diseases; Bravata DM et al.; BACKGROUND: Given the threat of bioterrorism and the increasing availability of electronic data for surveillance, surveillance systems for the early detection of illnesses and syndromes potentially related to bioterrorism have proliferated . PURPOSE: To critically evaluate the potential utility of existing surveillance systems for illnesses and syndromes related to bioterrorism . DATA SOURCES: Databases of peer-reviewed articles (for example, MEDLINE for articles published from January 1985 to April 2002) and Web sites of relevant government and nongovernment agencies . STUDY SELECTION: Reports that described or evaluated systems for collecting, analyzing, or presenting surveillance data for bioterrorism-related illnesses or syndromes . DATA EXTRACTION: From each included article, the authors abstracted information about the type of surveillance data collected; method of collection, analysis, and presentation of surveillance data; and outcomes of evaluations of the system . DATA SYNTHESIS: 17,510 article citations and 8088 government and nongovernmental Web sites were reviewed . From these, the authors included 115 systems that collect various surveillance reports, including 9 syndromic surveillance systems, 20 systems collecting bioterrorism detector data, 13 systems collecting influenza-related data, and 23 systems collecting laboratory and antimicrobial resistance data . Only the systems collecting syndromic surveillance data and detection system data were designed, at least in part, for bioterrorism preparedness applications . Syndromic surveillance systems have been deployed for both event-based and continuous bioterrorism surveillance . Few surveillance systems have been comprehensively evaluated . Only 3 systems have had both sensitivity and specificity evaluated . LIMITATIONS: Data from some existing surveillance systems (particularly those developed by the military) may not be publicly available . CONCLUSIONS: Few surveillance systems have been specifically designed for collecting and analyzing data for the early detection of a bioterrorist event . Because current evaluations of surveillance systems for detecting bioterrorism and emerging infections are insufficient to characterize the timeliness or sensitivity and specificity, clinical and public health decision making based on these systems may be compromised.

Lancet Infect Dis, 2004 Jun, 4(6), 337 - 48
PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings; Yang S et al.; Molecular diagnostics are revolutionising the clinical practice of infectious disease . Their effects will be significant in acute-care settings where timely and accurate diagnostic tools are critical for patient treatment decisions and outcomes . PCR is the most well-developed molecular technique up to now, and has a wide range of already fulfilled, and potential, clinical applications, including specific or broad-spectrum pathogen detection, evaluation of emerging novel infections, surveillance, early detection of biothreat agents, and antimicrobial resistance profiling . PCR-based methods may also be cost effective relative to traditional testing procedures . Further advancement of technology is needed to improve automation, optimise detection sensitivity and specificity, and expand the capacity to detect multiple targets simultaneously (multiplexing) . This review provides an up-to-date look at the general principles, diagnostic value, and limitations of the most current PCR-based platforms as they evolve from bench to bedside.

Eur J Intern Med, 2004 Apr, 15(2), 108 - 112
Nocardiosis in a tertiary care hospital on the island of Gran Canaria; Hemmersbach-Miller M et al.; Background: Nocardiosis is an uncommon but serious infection increasingly found in immunosuppressed persons . We describe 14 cases of nocardial infection seen at a tertiary hospital . Methods: All positive Nocardia cultures isolated from 1991 to 2002 were included . We analyzed predisposing factors, epidemiological and clinical features, laboratory and radiological findings, site(s) of infection, antimicrobial susceptibility pattern, treatment, and outcome . Factors related to mortality were analyzed . Results: Nineteen patients with a Nocardia isolate were identified and 14 were finally included . The most common predisposing factors included pulmonary diseases (71.4%), diabetes mellitus (35.7%), systemic diseases (28.6%) and immunosuppressive therapy (28.6%) . The site of infection was pulmonary in 12 cases (85.71%), cutaneous or subcutaneous in one case (7.1%), and disseminated in another case (7.1%) . The predominant clinical symptom was purulent expectoration (71.4%) while the predominant radiological pattern was a reticulonodular infiltrate (6/12, 50%) . Relapse was observed in one case (7.7%) and death in three cases (23.1%) . Diabetes mellitus was associated with the mortality rate (p=0.035) . Treatment was highly individualized, but trimethoprim (TMP)-sulfamethoxazole (SMX) was the combination most often used . Conclusions: Nocardiosis should be part of the differential diagnosis for patients presenting with pulmonary symptoms, soft tissue infection, or brain abscess.

Int J Med Inform, 2004 Jun 15, 73(5), 455 - 60
Computerized antimicrobial decision support: an offline evaluation of a database-driven empiric antimicrobial guidance program in hospitalized patients with a bloodstream infection; Mullett CJ et al.; INTRODUCTION: We developed a computerized antimicrobial guidance program based on the last 5 years of our laboratory culture data augmented by expert infectious disease logic . The program is designed to assist physicians with the targeting of empiric antimicrobials for hospitalized patients by tracking pathogenic bacteria and their evolving antimicrobial resistance profiles . Costs, toxicities, and environmental impact of antimicrobial use also influence the final recommendations . We undertook the following analysis to verify its potential safety and efficacy in hospitalized patients with a bloodstream infection . METHODS: We retrospectively enrolled all inpatients with a positive blood culture for a previously undetermined pathogen during the first 6 months of 2002 and determined the empiric therapy initiated within the 12h before and after the time of culture . Antimicrobial recommendations from the microbiologic decision support tool were then determined by matching specimen (blood), hospital unit, community- versus hospital-acquired category, age category, and gender . Generated antimicrobial recommendations were tailored to patient allergies, age category, and presence of pregnancy, lactation, or hepatic impairment . RESULTS: The microbiology laboratory recorded 226 unique patient/pathogen blood cultures during the study period . Physicians initiated effective empiric therapy in 150 of the 226 cases, for an effectiveness rate of 66% . The computer-guided therapy was effective in 195 of the 226 cases for a rate of 86% . A contingency table analysis showed 55 cases where the computer recommendation was effective but the physicians' selection was not, and eight cases where the physicians' antimicrobials were effective but the computer's were not (P < 0.0001) . DISCUSSION: For patients with a bloodstream infection, we found that our computer-guided statistically-derived antimicrobial therapy would potentially improve the rate of effectiveness of empirically chosen antimicrobials.

Med Res Rev, 2004 Jul, 24(4), 475 - 528
DNA minor groove binders as potential antitumor and antimicrobial agents; Baraldi PG et al.; DNA minor groove binders constitute an important class of derivatives in anticancer therapy . Some of these compounds form noncovalent complexes with DNA (e.g., distamycin A, Hoechst 33258, and pentamidine) while others DNA-binding compounds (such as CC-1065) cause cleavages in the DNA backbone . In this article, we have reviewed the minor groove binders currently in preclinical evaluation in the last years . Diarylamidines such as DAPI, berenil, and pentamidine; bis-benzimidazoles such as Hoechst 33258; ecteinascidins, pyrrololo {2,1-c}-{1,4}-benzodiazepines (PBDs), CC-1065, and distamycins are the classes discussed in this review article . A special section has been dedicated to hybrid molecules resulted by the combination of two minor groove binders, especially for derivatives of naturally occurring antitumor agents, such as anthramycin or the alkylating unit of the antibiotic CC-1065, and distamycin frames .

Curr Microbiol, 2004 Jun, 48(6), 441 - 6
Low-molecular-weight, biologically active compounds from marine Pseudoalteromonas species; Kalinovskaya NI et al.; We have examined the ability of marine Proteobacteria from the Pseudoalteromonas genus and Alteromonas macleodii to produce low-molecular-weight, biologically active compounds with antimicrobial and surface-active properties . A new marine bacterium, Pseudoalteromonas issachenkonii, exhibited a high level of biological activity and produced antifungal and hemolytic compounds . A detailed spectroscopic investigation based on UV, IR, high-resolution mass spectrometry, and 2D 1H and 13C nuclear magnetic resonance revealed that the former was indole-2,3-dione (isatin) . The chemical structure of red-brown pigment (C9H7N3OS3) responsible for hemolytic activity remained unclear . Four of the 15 strains studied (P . luteoviolacea, P . rubra, P . undina, and P . issachenkonii) produced cell-bound, two (P . elaykovii and P . carrageenovora) produced extracellular, and one strain (P . citrea) produced cell-bound and extracellular fatty acids and phospholipids with surface activity . Neither peptides nor glycolipids with surface activity were detected.

Phys Rev Lett . 2004 May 14;92(19):198304 . Epub 2004 May 13.
Molecular mechanism of Peptide-induced pores in membranes; Huang HW et al.; We suggest a physical mechanism by which antimicrobial peptides spontaneously induce stable pores in membranes . Peptide binding to a lipid bilayer causes an internal stress, or internal membrane tension, that can be sufficiently strong to create pores . Like detergents, peptides have a high affinity for the rim of the pore . Binding to the rims reduces the line tension and decreases the number of peptides causing the internal membrane tension . Consequently, the pore radius is stable . The pore formation resembles a phase transition.

J Indian Med Assoc . 2003 Sep;101(9):548, 557.
Microbes: therapeutic targets or therapeutic tools?
Mukherjee N.
Antimicrobial resistance has produced alarming situation worldwide . Use of antibiotics in large scale is one of the common cause for developing microbial resistance . Newer and newer antibiotics are coming for their use and more resistance problem is arising out . A complete new method of treatment by bacterial interference has been evolved . However, a new method of treatment has evolved ie, bacterial interference.

Int J Hematol, 2004 Apr, 79(3), 289 - 92
Successful treatment of chronic disseminated candidiasis with caspofungin and itraconazole in a patient with progressive acute leukemia and prolonged neutropenia; Hubel K et al.; Severe fungal infections remain a significant cause of morbidity and mortality in neutropenic patients undergoing dose-intensive chemotherapy for malignant diseases . Chronic disseminated candidiasis (CDC) is a life-threatening complication in neutropenic patients because of the lack of responsive hematopoietic precursor cells . Resolution of Candida organ lesions after hematopoietic reconstitution may take months . Here, we report the case of a 19-year-old neutropenic woman with relapsed acute myelogenous leukemia and candidiasis of liver, spleen, and kidneys . Antifungal treatment was initiated using fluconazole and caspofungin but was changed to itraconazole and caspofungin . Despite elevated C-reactive protein (CRP) levels and detectable Candida organ lesions, antileukemic therapy was restarted with interleukin 2 at the same time as antimicrobial treatment . Eight weeks after the start of interleukin therapy, CRP levels and organ lesions were decreased significantly irrespective of continuing neutropenia . This case report describes the successful treatment of CDC during neutropenia using combination antifungal therapy and suggests controlled studies to establish optimal therapeutic strategies.

Curr Opin Crit Care, 2004 Feb, 10(1), 59 - 64
Guidelines for community-acquired pneumonia in the ICU; Wilkinson M et al.; Community-acquired pneumonia remains a common and serious condition worldwide . Severe community-acquired pneumonia requiring ICU admission is a distinct entity with different pathogens, outcomes, and management . The mortality rate in severe community-acquired pneumonia can be more than 50% . Over the past decade, some international guidelines for the management of community-acquired pneumonia have been developed in an attempt to optimize patient care . These guidelines have developed prediction tools to direct clinicians in the management of community-acquired pneumonia, including when to admit a patient to the ICU and selecting appropriate investigations and antimicrobial therapy . The individual recommendations of these guidelines and the guidelines as a whole require further studies.

Curr Opin Infect Dis, 2004 Jun, 17(3), 185 - 91
How do viral infections predispose patients to bacterial infections?
Beadling C, Slifka MK.
PURPOSE OF REVIEW: Bacterial sepsis is a leading cause of death in the United States, accounting for over 200,000 fatalities annually . Approximately half of bacterial sepsis cases occur following acute respiratory infections, and the lungs are the most common organs to fail . Notably, outbreaks of respiratory viral infections are associated with an increased incidence or severity of bacterial co-infections, with normally innocuous infections often becoming fatal . Understanding the 'lethal synergism' associated with concomitant infections may point the way toward improved anti-sepsis treatments . RECENT FINDINGS: Murine models of viral and bacterial co-infection mimic the lethal synergism observed in humans and reveal at least two mechanisms of interaction . First, bacterial infiltration is heightened during acute viral infection . Secondly, the nature of responding cell populations is dramatically altered during concomitant infections . Although natural killer cells and macrophages are predominant cell populations responding to bacterial infection in a naive host, there is also a large T cell component that is activated upon viral infection . Inflammatory cytokines produced by these cells contribute to lethal immunopathology, and therapeutic strategies need to target the initial causative microbes as well as subsequent inflammatory responses . Current therapies directed only at the host immune response have not been overly successful, owing largely to difficulties in reversing the severe immunopathology associated with sepsis . SUMMARY: Respiratory viral infections may facilitate secondary bacterial infections and increase host immunopathology through the overproduction of inflammatory cytokines . Preventive measures, including vaccination and aggressive antimicrobial therapy early in the course of infection, may significantly reduce the morbidity and mortality of sepsis.

J Mol Biol, 2004 Jun 11, 339(4), 967 - 79
Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel adolase class; Bauer S et al.; Dihydroneopterin aldolase (DHNA) catalyses a retroaldol reaction yielding 6-hydroxymethyl-7,8-dihydropterin, a biosynthetic precursor of the vitamin, tetrahydrofolate . The enzyme is a potential target for antimicrobial and anti-parasite chemotherapy . A gene specifying a dihydroneopterin aldolase from Arabidopsis thaliana was expressed in a recombinant Escherichia coli strain . The recombinant protein was purified to apparent homogeneity and crystallised using polyethylenglycol as the precipitating agent . The crystal structure was solved by X-ray diffraction analysis at 2.2A resolution . The enzyme forms a D(4)-symmetric homooctamer . Each polypeptide chain is folded into a single domain comprising an antiparallel four-stranded beta-sheet and two long alpha-helices . Four monomers are arranged in a tetrameric ring, and two of these rings form a hollow cylinder . Well defined purine derivatives are found at all eight topologically equivalent active sites . The subunit fold of the enzyme is related to substructures of dihydroneopterin triphosphate epimerase, GTP cyclohydrolase I, and pyruvoyltetrahydropterin synthase, which are all involved in the biosynthesis of pteridine type cofactors, and to urate oxidase, although some members of that superfamily have no detectable sequence similarity . Due to structural and mechanistical differences of DHNA in comparison with class I and class II aldolases, a new aldolase class is proposed.

Trends Pharmacol Sci, 2004 Jun, 25(6), 306 - 10
Intravenous immunoglobulin for infectious diseases: back to the pre-antibiotic and passive prophylaxis era?
Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV.
The dramatic increase in both the number of novel infectious agents and resistance to antimicrobial drugs has incited the need for adjunct therapies in the war against infectious diseases . Exciting recent studies have demonstrated the use of antibodies in the form of intravenous immunoglobulin (IVIg) against infections . By virtue of the diverse repertoire of immunoglobulins that possess a wide spectrum of antibacterial and antiviral specificities, IVIg provides antimicrobial efficacy independently of pathogen resistance and represents a promising alternative strategy for the treatment of diseases for which a specific therapy is not yet availablePublication Types:

	Review
	Review, Tutorial

What Is Anthrax?, What Is Environmental Microbiology?, What Is Listeria Monocytogenes?, What Is Bioreactor?, What Is Biofilm?, a, Microbiology, i, Bacteria, i, Microorganisms, n, Bacteriology, s, Microorganism, o, Streptococcal, e, Erythromycin, r, Photobacteria, s, Bacillus, i, Salmonella, o, Bacteriological, s, Escherichia coli, n, Yeasts, i, Denitrifying, o, Bacteriological, a, Bacteriological, r, Ciprofloxacin, o, Escherichia coli, o, Cell suspensions, s, Escherichia coli, n, Microbiological, e, Pseudomonas aeruginosa, a, Streptococci, r, Gram negative, e, Enterobacteriacea, a, Pichia

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005