Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S147 - 56 Restricting the selection of antibiotic-resistant mutants: a general strategy derived from fluoroquinolone studies; Zhao X et al.; Studies with fluoroquinolones have led to a general method for restricting the selection of antibiotic-resistant mutants . The strategy is based on the use of antibiotic concentrations that require cells to obtain 2 concurrent resistance mutations for growth . That concentration has been called the "mutant prevention concentration" (MPC) because no resistant colony is recovered even when >10(10) cells are plated . Resistant mutants are selected exclusively within a concentration range (mutant selection window) that extends from the point where growth inhibition begins, approximated by the minimal inhibitory concentration, up to the MPC . The dimensions of the mutant selection window can be reduced in a variety of ways, including adjustment of antibiotic structure and dosage regimens . The window can be closed to prevent mutant selection through combination therapy with > or =2 antimicrobial agents if their normalized pharmacokinetic profiles superimpose at concentrations that inhibit growth . Application of these principles could drastically restrict the selection of drug-resistant pathogens. Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S133 - 7 Consequences of inaction: importance of infection control practices; Boyce JM; The increasing prevalence of antimicrobial-resistant pathogens in health care facilities is due in large part to overuse of antibiotics and poor compliance with recommended infection control practices . To control the spread of such pathogens, health care facilities must reduce overuse and abuse of antibiotics, and they must implement new multidisciplinary programs to improve hand hygiene practices among health care workers and improve compliance with recommended barrier precautions. Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S118 - 23 Using internet discussion of antimicrobial susceptibility databases for continuous quality improvement of the testing and management of antimicrobial resistance; O'Brien TF et al.; Accurate results from the world's microbiology laboratories are essential for care of patients, control of hospital and community infections, and global epidemiology . Yet those laboratories differ greatly in their access to supplies, published literature and standards, training courses, peer interaction, and mandated quality control . Because much of what is needed is information, new information technology should help . In particular, measurements of susceptibility to antimicrobial agents, now increasingly filed in electronic databases, exhibit many kinds of variances due both to test performance and to the diversity of bacteria and of their mechanisms of resistance . In industry, workers' ongoing evaluation of variances in measurements of performance has been the basis of management programs of continuous quality improvement . Examples suggest how collegial evaluation of variances in shared susceptibility test data might similarly improve quality not only of testing but also of other aspects of the management of antimicrobial resistance . Internet access is now making such ongoing evaluation and discussion increasingly possible in most parts of the world. Clin Infect Dis, 2001 Sep 15, 33 Suppl 3, S116 - 7 Globalization of antimicrobial resistance: epidemiological challenges; Williams RJ; Globalization of antimicrobial resistance is a reality, but before the relative impact of global versus local spread of resistant microorganisms can be quantified, surveillance capacity and information transfer must be greatly enhanced. Clin Microbiol Infect, 2001, 7 Suppl 3, 30 - 8 Community-acquired pneumonia: the evolving challenge; Finch R; Community-acquired pneumonia (CAP) is a common disorder that has been the focus of a major international research effort to define its epidemiology, etiology and management . The microbial etiology of CAP is complex and severity assessment is important in identifying at-risk populations as well as defining therapeutic strategies . Laboratory investigations rarely influence initial therapy, which remains empirical . Guidelines have been developed in many countries in response to the need to optimize management and outcomes . However, many of these guidelines have been based on expert opinion rather than robust evidence . New evidence-based guidelines have been developed that take into account disease severity, the local distribution of pathogens and their likely susceptibility to antimicrobials, and that include newer treatment options . Macrolide and fluoroquinolone antimicrobials feature heavily in these new treatment recommendations . Promising new therapies continue to emerge that may offer advantages over fluoroquinolones and macrolides, in particular with regard to the problem of resistance . Of these, the ketolides are of special interest . Telithromycin, the first ketolide antibacterial, has been evaluated in the treatment of > 700 patients with CAP . A once-daily oral dose of telithromycin 800 mg for 7-10 days produces clinical and bacteriological success rates > 90% and equivalent to standard comparator agents, whilst maintaining efficacy against resistant pathogens. Clin Microbiol Infect, 2001, 7 Suppl 3, 24 - 9 Pharmacodynamic and pharmacokinetic considerations in antimicrobial selection: focus on telithromycin; Drusano G; The effectiveness of empirical treatment for respiratory tract infections (RTIs) with commonly available antimicrobials is threatened by the development of microbial resistance and cross-resistance between treatments . Pharmacokinetic and pharmacodynamic profiling of antimicrobial agents is increasingly being used to select the most appropriate treatment and dosage schedules for RTIs . In addition to enhancing management strategies with existing treatments, these profiles have played a key part in identifying dosage schedules for a new family of semisynthetic antimicrobials, the ketolides . The first member of this family, telithromycin, has potent activity against both common and atypical pathogens involved in RTIs and does not induce resistance to the macrolide-lincosamide-streptogramin B (MLS(B)) antimicrobials in vitro . Its pharmacokinetic profile reveals that telithromycin can be administered once daily without regard for meals, requires no dose reduction in elderly patients or those with hepatic impairment, and penetrates rapidly into respiratory tissues and fluids, a feature probably related to its ability to concentrate inside white blood cells . Pharmacodynamic studies indicate that the area under the concentration-time curve (AUC):minimum inhibitory concentration (MIC) and the peak plasma concentration (Cmax):MIC ratios are important determinants of bacteriological outcome with telithromycin . Telithromycin has a high AUC:MIC ratio compared with macrolide antimicrobials, which is expected to result in enhanced antimicrobial activity . These properties of telithromycin, combined with its good tolerability and low propensity for drug interactions, provide the basis for potent and reliable treatment of RTIs with a convenient, once-daily regimen. Clin Microbiol Infect, 2001, 7 Suppl 3, 18 - 23 Safeguarding future antimicrobial options: strategies to minimize resistance; Leclercq R; Current antimicrobial therapy for community-acquired respiratory tract infections (RTIs) is empirical and is influenced by local differences in etiology and bacterial susceptibility . As the rates of resistance and cross-resistance to currently available classes of antimicrobial agents increase, their effectiveness becomes compromised . These issues demand improved strategies for antimicrobial usage, and the development of new agents that do not select resistance are essential to safeguard future antimicrobial efficacy . Strategies to minimize antimicrobial resistance among common RTIs include reducing antimicrobial consumption and controlling the development and spread of resistance through appropriate prescribing and the use of short-duration, once-daily treatments to improve patient compliance . Importantly, the ketolides, which are a new family of antimicrobials, have been recently developed specifically for the treatment of community-acquired RTIs . The first member of this new family, telithromycin, has been shown to have potent activity against common and atypical respiratory pathogens, including beta-lactam- and macrolide-resistant strains, and has a low potential to select for or induce cross-resistance . These properties, combined with its good tolerability across patient groups, make telithromycin an attractive option for the first-line empiric treatment of RTIs with the potential to limit the future development of resistance. Nippon Ronen Igakkai Zasshi, 2001 Jul, 38(4), 440 - 3 {Defensins as a mechanism of host defense and innate immunity}; Tomita T et al.; Antimicrobial peptides, including beta-defensins, are thought to be effective agents against opportunistic infections . In humans, three beta-defensins have been identified . The first human beta-defensin, hBD-1, is predominantly expressed in epithelia of the urogenital tract and has been reported to be constitutive . The second and third human beta-defensins, hBD-2 and hBD-3, were isolated from psoriatic skin and found to be predominantly expressed in skin and respiratory tract . Of note, the hBD-2 gene expression is inducible by various proinflammatory agents such as TNF-alpha, IL-1 beta, IL-8, LPS, bacteria, and yeasts . It has been shown that LPS-induced expression of hBD-2 in human tracheobronchial epithelial cells requires CD14, which may complex with Toll-like receptors (TLRs) to ultimately activate NF-kappa B . In addition, beta-defensins have been recently reported to promote immune responses by recruiting dendritic and T cells . Defensins may play a key role in the mechanism of host defense and innate immunity . These defensins, including hBD-2, might provide a new therapeutic approach to infectious diseases. Drug Discov Today, 2001 Sep 1, 6(17), 887 - 892 Finding drug targets in microbial genomes; Read TD et al.; In this era of genomic science, knowledge about biological function is integrated increasingly with DNA sequence data . One area that has been significantly impacted by this accumulation of information is the discovery of drugs to treat microbial infections . Genome sequencing and bioinformatics is driving the discovery and development of novel classes of broad-spectrum antimicrobial compounds, and could enable medical science to keep pace with the increasing resistance of bacteria, fungi and parasites to current antimicrobials . This review discusses the use of genomic information in the rapid identification of target genes for antimicrobial drug discovery. FEBS Lett, 2001 Aug 24, 504(1-2), 5 - 10 Calcitermin, a novel antimicrobial peptide isolated from human airway secretions; Cole AM et al.; The human airways are protected from pathogenic colonization by a blanket of fluid impregnated with innate antimicrobial effector molecules . Among several previously uncharacterized components, we isolated a peptide that had activity primarily targeting Gram-negative bacteria . We named the peptide 'calcitermin' since its amino acid sequence and mass were equivalent to the 15 C-terminal residues of the S100 protein, calgranulin C . The antimicrobial activity of calcitermin was enhanced in acidic buffers (pH 5.4) and in the presence of micromolar concentrations of ZnCl(2) . Analysis revealed a putative zinc-binding consensus sequence as well as an alpha-helical conformation in structure-promoting solvents. Semin Respir Infect, 2001 Jun, 16(2), 91 - 101 Pathogenesis of Histoplasma capsulatum; Woods JP et al.; Histoplasma capsulatum is well adapted to be infectious and pathogenic for humans . As a soil fungus with no known requirement for interacting with a mammalian host as part of an obligate lifecycle, its plethora of strategies for successful pathogenesis is particularly remarkable . These features include the dimorphic mold-yeast transition, entry into host macrophages, subcellular localization, intracellular survival and proliferation during active infection, and persistence during clinically inapparent infection with the capacity for reactivation . To thrive within the harsh environment of a professionally phagocytic and antimicrobial host cell, H . capsulatum displays mechanisms for modulating its microenvironmental pH level, resisting host reactive oxygen and nitrogen intermediates and degradative enzymes, and withstanding nutrient starvation conditions, including acquisition of iron and calcium and biosynthesis of nucleic acid precursors . Attention has been focused on identifying virulence-associated phenotypic traits and genes that are differentially expressed under relevant conditions, such as yeast morphotype-specific genes and genes that are up-regulated during infection . These studies, together with the increasing ability to perform molecular genetic manipulations in this fungus, may yield novel antifungal drug or vaccine targets as well as elucidating pathogenic mechanisms . Can Respir J, 2001 Jul-Aug, 8(4), 255 - 60 The use of guidelines for the empirical treatment of hospital-acquired pneumonia; Miletin MS et al.; BACKGROUND: Several practice guidelines for the empirical antimicrobial treatment of hospital-acquired pneumonia (HAP) have been developed, but the acceptance and use of such guidelines are unknown . OBJECTIVE: To assess physicians' use of empirical HAP guidelines published by the American Thoracic Society (ATS) and by The University Health Network, Toronto, Ontario . DESIGN: A retrospective assembly and chart review . SETTING: A university teaching hospital . PATIENTS: One hundred fifteen consecutive patients who had been diagnosed with pneumonia more than 48 h after admission to hospital over a 10-month period . RESULTS: The charts of 115 patients were reviewed . Seventy-five patients (65%) were treated empirically . Forty patients (35%) were treated based on microbiological data that were available before the initiation of antibiotics . Patients who received nonempirical treatment for HAP had a significantly greater acuity of illness than the empirically treated group . Thirty-seven patients (49%) who received empirical therapy were treated according to either ATS or hospital guidelines for HAP . The use of guideline-concordant antimicrobial therapy had no measurable effect on in-hospital mortality (eight of 37 patients {21.6%} versus seven of 38 patients {18.4%}, P=0.96) or median length of stay (19 days versus 21 days, P=0.30) . Patients whose treatment did not follow guideline recommendations tended to receive appropriate antimicrobial coverage more often than did those patients whose treatment was guideline concordant (15 of 18 patients {83%} versus six of 11 patients {55%}, P=0.49) . CONCLUSIONS: Institutional and ATS guidelines for the empirical treatment of HAP are less widely used than would be predicted by chance at The University Health Network . The clinical utility of these guidelines remains to be proven. J Endotoxin Res, 2000, 6(6), 459 - 62 LPS-induced immune response in Drosophila; Imler JL et al.; The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity . In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity . We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection . We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors . However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes . These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila. J Nat Prod, 2001 Aug, 64(8), 1095 - 7 Samioside, a new phenylethanoid glycoside with free-radical scavenging and antimicrobial activities from Phlomis samia; Kyriakopoulou I et al.; A new phenylethanoid glycoside, samioside, was isolated from the aerial parts of Phlomis samia and identified as 1-O-3,4-(dihydroxyphenyl)ethyl beta-D-apiofuranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-4-O-caffeoyl-beta-D-glucopyranoside (1) . In addition, one known phenylethanoid glycoside and three known flavonoids were identified as acteoside (2), apigenin, chrysoeriol, and ermanin, respectively . The structure of 1 was elucidated on the basis of its spectroscopic data . Samioside (1) demonstrated scavenging properties toward the DPPH radical and antimicrobial activity against Gram-positive and -negative bacteria. Biochem Biophys Res Commun, 2001 Aug 31, 286(4), 820 - 5 IsCT, a novel cytotoxic linear peptide from scorpion Opisthacanthus madagascariensis; Dai L et al.; A novel cytotoxic linear peptide, IsCT, was characterized from scorpion Opisthacanthus madagascariensis . It is a linear peptide with a molecular weight of 1501.9 Da composed of 13 amino acid residues without cysteines . MS/MS analysis showed that its C-terminal is amidated . The identity of IsCT is re-confirmed by comparing the chemical synthesized peptide with the natural one . IsCT demonstrated antimicrobial activity against both gram-positive and gram-negative bacteria and hemolytic activity to sheep red blood cells . Also, it can release histamine from rat peritoneal mast cells . The CD absorption suggested that IsCT had an alpha-helix configuration in aqueous TFE . IsCT is one of the shortest natural cytotoxic peptides described, and it will be a suitable model for studying peptide-lipid interactions . Infect Control Hosp Epidemiol, 2001 Jun, 22(6), 379 - 82 Differences in antimicrobial susceptibility among hospitals in an integrated health system; Lubowski TJ et al.; We evaluated the differences in antimicrobial susceptibility among hospitals in three different integrated healthcare systems . Each system provided antibiogram-susceptibility reports from representative hospitals . Reports were analyzed for statistically significant differences between hospitals in a given system for nine important organisms . We found numerous significant interhospital differences in antimicrobial-susceptibility patterns within health systems . For this reason, the practice of combining antibiotic-susceptibility data into a systemwide antibiogram should be discouraged. Yonsei Med J, 2001 Aug, 42(4), 457 - 70 Helicobacter pylori infection in Korea; Park IS et al.; Helicobacter pylori is a gram-negative bacterium that was first isolated in 1982 . Since then, H . pylori infection in humans has been shown to be associated with gastritis, peptic ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma as well . The epidemiology, transmission, and pathogenicity of H . pylori has been a subject of intensive study . Successful treatment improves the cure rate of peptic ulcerations and treatment with antimicrobials also decreases the recurrence rate of these diseases . Better regimens having less toxicity and a good eradication rate have also been developed . A better understanding of the pathophysiologic mechanisms relating to H . pylori induced mucosal damages would result in more options for the prevention of peptic ulcers and carcinogenesis . Korea has a relatively high incidence of H . pylori infection and gastric cancer . Growing interest has developed in view of its importance in being associated with various gastroduodenal diseases . Furthermore, along with a high incidence of H . pylori-related disease in Korea, because the interaction between H . pylori, host factors and environmental factors is important in disease pathogenesis, we need to have precise data on the characteristics of H . pylori-related diseases that occur in Korea . In the present report we review the epidemiology, transmission route, diagnosis, pathogenesis, treatment methods and relationship with gastroduodenal diseases with in special references to basic and clinical data that have been published. J Mol Biol, 2001 Aug 24, 311(4), 789 - 801 Crystal structures of cystathionine gamma-synthase inhibitor complexes rationalize the increased affinity of a novel inhibitor; Steegborn C et al.; Cystathionine gamma-synthase catalyzes the committed step of methionine biosynthesis . This pathway is unique to microorganisms and plants, rendering the enzyme an attractive target for the development of antimicrobials and herbicides . We solved the crystal structures of complexes of cystathionine gamma-synthase (CGS) from Nicotiana tabacum with inhibitors of different compound classes . The complex with the substrate analog dl-E-2-amino-5-phosphono-3-pentenoic acid verifies the carboxylate-binding function of Arg423 and identifies the phosphate-binding pocket of the active site . The structure shows the function of Lys165 in specificity determination and suggests a role for the flexible side-chain of Tyr163 in catalysis . The importance of hydrophobic interactions for binding to the active-site center is highlighted by the complex with 3-(phosphonomethyl)pyridine-2-carboxylic acid . The low affinity of this compound is due to the non-optimal arrangement of the functional groups binding to the phosphate and carboxylate-recognition site, respectively . The newly identified inhibitor 5-carboxymethylthio-3-(3'-chlorophenyl)-1,2,4-oxadiazol, in contrast, shows the highest affinity to CGS reported so far . This affinity is due to binding to an additional active-site pocket not used by the physiological substrates . The inhibitor binds to the carboxylate-recognition site, and its tightly bent conformation enables it to occupy the novel binding pocket between Arg423 and Ser388 . The described structures suggest improvements for known inhibitors and give guidelines for the development of new lead compounds . Int J Food Microbiol, 2001 Aug 5, 67(3), 227 - 39 Modelling the effects of (green) antifungals, droplet size distribution and temperature on mould outgrowth in water-in-oil emulsions; ter Steeg PF et al.; Prevention of fungal spoilage is a key microbiological issue for the shelf life of fat spreads . Our aim was to assess and model the scope of (natural) antimicrobials for extending shelf life of spreads (water-in-oil emulsions) . Production conditions were established to make 60% model fat spreads with reproducible droplet size distributions . The mould vulnerabilities ranged from 1 to 20 weeks . The system allowed feasibility testing of lytic enzymes (Novozym 234) and LMW compounds against Penicillium roqueforti, a key-spoilage mould . The action of Novozym 234, carvacrol, undecanol and dihydrocarveol was benchmarked against sorbate and preservative-free controls under ambient and chilled conditions . Novozym 234 was ineffective to prevent outgrowth of P . roqueforti . Carvacrol, undecanol and dihydrocarveol had limited effects on shelf-life extension compared to sorbate . Fungal growth boundaries of (un-)preserved spreads were modelled . The emulsion droplet size distribution (DSD) was first captured in a mechanistic parameter DSD-I (I = Influence) . DSD-I was a move away from the mean droplet diameter D3,3 as sole quantitative droplet-size distribution parameter for mould susceptibility of emulsions . DSD-I is a combination of available water droplets and surface area to initiate and sustain fungal outgrowth . Followup experiments showed that modelling D3,3 and distribution width (e(sigma)) instead of DSD-I gave better results for emulsions with high e(sigma) . Empirical predictive models were subsequently developed for the effects of D3,3, e(sigma) and undissociated sorbic acid (HSO) on the shelf life of emulsions. J Air Waste Manag Assoc, 2001 Aug, 51(8), 1219 - 26 Investigation of the potential antimicrobial efficacy of sealants used in HVAC systems; Foarde KK et al.; Recent experiments confirm field experience that duct cleaning alone may not provide adequate protection from regrowth of fungal contamination on fiberglass duct liner (FGDL) . Current recommendations for remediation of fungally contaminated fiberglass duct materials specify complete removal of the materials . But removal of contaminated materials can be extremely expensive . Therefore, a common practice in the duct-cleaning industry is the postcleaning use of antimicrobial surface coatings with the implication that they may contain or limit regrowth . Little information is available on the efficacy of these treatments . This paper describes a study to evaluate whether three commercially available antimicrobial coatings, placed on a cleaned surface that 1 year previously had been actively growing microorganisms, would be able to prevent regrowth . The three coatings contained different active antimicrobial compounds . All three of the coatings were designed for use on heating, ventilation, and air conditioning (HVAC) system components or interior surfaces of lined and unlined duct systems . Coating I was a polyacrylate copolymer containing zinc oxide and borates . Coating II was an acrylic coating containing decabromodiphenyl oxide and antimony trioxide . Coating III was an acrylic primer containing a phosphated quaternary amine complex . The study included field and laboratory assessments . The three treatments were evaluated in an uncontrolled field setting in an actual duct system . The laboratory study broadened the field study to include a range of humidities under controlled conditions . Both static and dynamic chamber laboratory experiments were performed . The results showed that two of the three antimicrobial coatings limited the regrowth of fungal contamination, at least in the short term (the 3-month time span of the study); the third did not . Before use in the field, testing of the efficacy of antimicrobial coatings under realistic use conditions is recommended because antimicrobials have different baseline activities and interact differently with the substrate that contains them and their local environment. J Pharm Pharmacol, 2001 Aug, 53(8), 1047 - 67 Chitosan: some pharmaceutical and biological aspects--an update; Singla AK et al.; Chitosan, a natural polysaccharide, is being widely used as a pharmaceutical excipient . It is obtained by the partial deacetylation of chitin, the second most abundant natural polymer . Chitosan comprises a series of polymers varying in their degree of deacetylation, molecular weight, viscosity, pKa etc . The presence of a number of amino groups permit chitosan to chemically react with anionic systems, thereby resulting in alteration of physicochemical characteristics of such combinations . Chitosan has found wide applicability in conventional pharmaceutical devices as a potential formulation excipient, some of which include binding, disintegrating and tablet coating properties . The polymer has also been investigated as a potential adjuvant for swellable controlled drug delivery systems . Use of chitosan in novel drug delivery as mucoadhesive, gene and peptide drug administration via the oral route as well as its absorption enhancing effects have been explored by a number of researchers . Chitosan exhibits myriad biological actions, namely hypocholesterolemic, antimicrobial and wound healing properties . Low toxicity coupled with wide applicability makes it a promising candidate not only for the purpose of drug delivery for a host of drug moieties (antiinflammatories, peptides etc.) but also as a biologically active agent . It is the endeavour of the present review to provide an insight into the biological and pharmaceutical profile of chitosan . Various investigations carried out recently are reported, although references to research performed on chitosan prior to the recent reviews have also been included, where appropriate. Vestn Ross Akad Med Nauk, 2001, (6), 45 - 52 {Free radical oxidation as a link of early and prolonged adaptation to environmental factors}; Velichkovskii BT; Analyzing his own findings and the data available in the literature, the author has found that free radicals are a connecting link in the development of early and prolonged adaptation . With rapid adaptation, they make a weighty contribution to the body's bactericidal protection and antimicrobial constitutional immunity . This role is mainly played by the oxygen-dependent phagocytic bactericidal system that generates active oxygen forms and by the inducible arginine-dependent connective tissue cell system that synthesizes nitrogen oxide . While performing, the above enzymatic systems spend their cell energy resources on two concurrent processes: the formation of free radical products and the work of ionic pumps that restore an intracellular ionic and osmotic balance . This causes the accelerated expenditure of the body's energy "currency" ATP and the development of energy deficiency in the cells and tissues . Energy shortage serves as a signal for triggering the cellular genetic apparatus to primarily induce the increased development of the cell energy system, namely that of mitochondria, and the activation of the key systems responsible for steady-state long-term individual adaptation of the immune system, antioxidative protection, etc . It has been now ascertained that there is a common pathogenetic link (excessive production of free radicals) in the mechanism responsible for the influence of not only infections on the body, but other environmental factors (fibrogenic dust, ionizing or ultraviolet radiation, cooling, toxic agents oxidized on cytochrome P-450, hypoxia, hyperoxia, etc.) and vital functions (physical overstrain, emotional stress, informational overload, etc.) . The above factors all cause the same metabolic change in different ways: the production of higher quantities of active oxygen forms, nitrogen oxide, and other radical products . So the generation of free radicals is an universal connecting link of early and prolonged adaptation . The fact that there is a common link (the excessive production of radicals) in the mechanism of influence of environmental factors and vital activities makes the most important biological reserve (cross adaptation that lies in higher resistance to the whole complex of active influences at adaptation to one of them) serve as a preventive means . The most rapid increase in the production of free radicals and the development of energy-rich products are achieved by hypoxia . So the adaptive and preventive effect of dosage hypoxia are the most pronounced. J Immunol Methods, 2001 Oct 1, 256(1-2), 65 - 76 Detection of beta-defensins secreted by human oral epithelial cells; Diamond DL et al.; Human beta-defensins are antimicrobial peptides that may be critical in the innate immune response to infection . hBD1 and hBD2 are expressed in oral epithelial cells and are detected near the surface of oral tissue, consistent with a role in the epithelial protective barrier function . In this report, we examine secretion of beta-defensins in vitro and in biological fluid using ProteinChip(R) Array, surface enhanced laser desorption/ionization (SELDI) technology combined with time-of-flight mass spectrometry . We show that the 47-amino acid form of hBD1 and the 41-amino acid form of hBD2 are the major secreted forms . These forms are both expressed and secreted under conditions anticipated from previous analysis of beta-defensin mRNAs; specifically, hBD1 is detected in culture supernatant from both unstimulated and stimulated cells, and hBD2 is detected only in stimulated cells . Identity of hBD1 and hBD2 was confirmed by immunocapture on the ProteinChip surface . Both peptides are also present in gingival crevicular fluid that accumulates between the tissue and tooth surface, although hBD1 is also found in several smaller forms suggesting extracellular proteolysis . This methodology offers several technical advantages for detection of defensins in biological fluids, including ease and speed of screening, no need for HPLC preliminary processing, and small sample size. J Chromatogr Sci, 2001 Aug, 39(8), 339 - 44 A simplex-optimized chromatographic separation of fourteen cosmetic preservatives: analysis of commercial products; Marengo E et al.; An ion-interaction high-performance liquid chromatography (HPLC)-diode-array detection method is developed and optimized for the separation of typical antimicrobial agents used in cosmetics and hygiene products . The most used preservatives contain different molecular structures, different functionalities, and are characterized by different chemical properties . Organic acids, alkyl esters of benzoic acids, alkyl p-hydroxy benzoic acids (parabens), phenol derivatives, and carbanilides represent the most used preservatives, and are often present in multicomponent mixtures . In order to develop a multicomponent method to be used in quality control analysis, the ion-interaction reagent reversed-phase HPLC technique seems to be particularly suitable, because it allows for the simultaneous separation of acidic, basic, and neutral species . The experimental conditions of the method are developed by OVAT (one variable at a time) treatment and further optimized by a multivariate approach based on a Simplex algorithm that works on a desirability function targeted to maximize the resolution in a multicomponent mixture . The new method proposed that is able to simultaneously separate fourteen preservatives is applied in the analysis of commercial products. Immunol Rev, 2001 Jun, 181, 158 - 69 Ligands for natural killer cell receptors: redundancy or specificity; Cerwenka A et al.; Several inhibitory and activating receptors involved in natural killer cell activation have been characterized . The increasing knowledge about their ligands, including classical MHC class I molecules, non-classical MHC class I molecules and MHC class I-related molecules, is shedding new light on the targets of innate immune recognition . While classical MHC class I molecules are constitutively expressed, some MHC class I-related (MIC) molecules, however, are stress-induced by ill-defined stimuli . Two families of ligands for the human activating NKG2D receptor have been identified . These are the MIC proteins encoded by two highly polymorphic genes within the MHC class I and the retinoic acid-inducible early gene-1-like (also designated UL16-binding) proteins encoded by genes outside the MHC . For the mouse NKG2D receptor, one family, containing at least five distinct ligands, has been described . A better understanding about how targets signal their distress, which renders them susceptible to natural killer (NK)-cell attack, will help to define the role of NK cells in antimicrobial and antitumor immunity and transplantation. Obstet Gynecol Clin North Am, 2001 Sep, 28(3), 553 - 69 Pneumonia in pregnancy; Ramsey PS et al.; Although the advent of broad-spectrum antibiotics has markedly improved the maternal outcomes of pneumonia complicating pregnancy, pneumonia remains a significant condition that may complicate pregnancy . This article has reviewed the inherent physiologic respiratory changes that accompany pregnancy and the common causes of pneumonia in the pregnant woman . The clinical course of bacterial pneumonia seems to be minimally altered by pregnancy, whereas viral pneumonia carries a significantly worse prognosis when encountered during gestation . Prompt diagnosis, the initiation of respiratory support, and appropriate antimicrobial/antiviral therapy are key components of therapy for women in whom pregnancy is complicated by pneumonia . Because preterm labor frequently accompanies pneumonia, women should be monitored closely for the occult onset of preterm labor and appropriate interventions initiated if indicated . Perhaps even more important than interventions to treat acute pneumonia are efforts directed at active immunization or prophylactic therapy to prevent the development of pneumonia in select patient populations . The combination of these efforts is essential to optimize medical care for pregnant women. Clin Infect Dis, 2001 Sep 15, 33(6), 817 - 28 Epub 2001 Aug 06. Infectious diseases journals on the World Wide Web: attractions and limitations; Abbas UL et al.; Online infectious diseases (ID) journals are an increasingly common Web phenomenon . We performed a study of practices in this evolving area that make these sites more usable and useful from the perspective of ID physicians . The Web sites of 18 journals pertaining to general ID and infection control and hospital epidemiology were evaluated for a set of 24 Web interface characteristics and online features . Journals hosted by the High Wire Press (Antimicrobial Agents and Chemotherapy, Infection and Immunity, and the Journal of Antimicrobial Chemotherapy) and the University of Chicago Press (The Journal of Infectious Diseases and Clinical Infectious Diseases) best fulfilled our criteria . Electronic reference linking, archives, e-mail alerts, and links to external resources are some of the features of electronic journals that users in the ID specialty may find especially useful. Crit Care, 2001 Aug, 5(4), 189 - 95 Epub 2001 Jun 28. Optimizing antibiotic therapy in the intensive care unit setting; Kollef MH; Antibiotics are one of the most common therapies administered in the intensive care unit setting . In addition to treating infections, antibiotic use contributes to the emergence of resistance among pathogenic microorganisms . Therefore, avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will help to improve patient outcomes while minimizing further pressures for resistance . This review will present several strategies aimed at achieving optimal use of antimicrobial agents . It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilization and its effectiveness . Only in this way can the impact of interventions aimed at improving antibiotic use (e.g . antibiotic rotation, de-escalation therapy) be evaluated at the local level. Adv Perit Dial, 2001, 17, 180 - 90 The case for oral treatment of peritonitis in continuous ambulatory peritoneal dialysis; Passadakis P et al.; Among several regimes used in the oral treatment of continuous ambulatory peritoneal dialysis (CAPD)--related peritonitis, ciprofloxacin and ofloxacin showed the higher treatment efficacy, with an overall cure rate of 80% over a treatment duration of 10-16 days . The antimicrobial activity of these agents against gram-positive episodes was equal to or even higher than that against other peritonitis episodes, and the effectiveness of oral ciprofloxacin can be further increased either by an additional intraperitoneal dose for the first 1-5 days, or by a simultaneous intraperitoneal dose of vancomycin in the first 24 hours . Clinical resistance to the new quinolones has been uncommon . The possibly increasing resistance to ciprofloxacin is a consequence of suboptimal dosing, with the resulting low local concentrations of the antibiotic . Oral treatment with quinolones provides a good therapeutic alternative to more widely used antibiotics for initial treatment of peritonitis episodes . However, more extensive data from comparative randomized studies with agents administered orally and intraperitoneally would be able to clearly elucidate the overall safety and success of oral treatment of PD-related peritonitis with quinolones or any new agent. Rev Med Chil, 2001 Jun, 129(6), 643 - 6 {In vitro antimicrobial susceptibility of Helicobacter pylori strains: isolation of strains resistant to clarithromycin}; Gonzalez C et al.; BACKGROUND: Our laboratory has carried out an epidemiological surveillance of Helicobacter pylori antimicrobial susceptibility since 1997 . AIM: To report the antimicrobial susceptibility of H pylori strains, isolated in Chile from August 1997 to August 2000 . MATERIAL AND METHODS: Ninety one H pylori strains, obtained from antral gastric biopsies during upper gastrointestinal endoscopies were studied . Susceptibility towards clarithromycin, amoxicillin, bismuth subcitrate and metronidazole was studied by an agar diffusion technique . RESULTS: All strains were susceptible to amoxicillin and two strains were resistant to clarithromycin . Forty two percent of strains were resistant to metronidazole and 13% were resistant to bismuth subcitrate . CONCLUSIONS: These results underscore the need to maintain an epidemiological surveillance of H pylori antimicrobial susceptibility, to modify its eradication therapy accordingly. Planta Med, 2001 Aug, 67(6), 580 - 4 Essential oil composition and antimicrobial activity of three Zingiberaceae from S.Tomé e Príncipe; Martins AP et al.; The essential oil composition of three Zingiberaceae widely used as medicinal aromatic plants from S . Tome and Principe: Aframomum danielli (Hook . f.) K . Schum., Curcuma longa L . and Zingiber officinale Rosc . was studied . Two samples of the essential oils from fruit of A . danielli and from rhizomes of the other two species, were obtained by hydrodistillation and analyzed by GC, GC-MS, and (13)C-NMR . The essential oil from fruits of A . danielli has been studied for the first time and was characterised by its high content of monoterpenes, with 1,8-cineole (25.5 - 34.4 %) the major constituent, followed by beta-pinene (14.1 - 15.2 %) and alpha-terpineol (9.9 - 12.1 %) . Essential oils from the rhizomes of C . longa contained a lower content of ar-turmerone (4.0 - 12.8 %) than those reported in the literature for C . longa from other origins (24.7 - 31.4 %), whereas the results for Z . officinale essential oils were in accordance with the literature data . The essential oils of A . danielli and Z . officinale showed antimicrobial activity against all Gram-positive and Gram-negative bacteria tested, as well as against yeasts and filamentous fungi, using the agar diffusion method. J Immunol, 2001 Sep 1, 167(5), 2861 - 8 Human IgA activates the complement system via the mannan-binding lectin pathway; Roos A et al.; The recently identified lectin pathway of the complement system, initiated by binding of mannan-binding lectin (MBL) to its ligands, is a key component of innate immunity . MBL-deficient individuals show an increased susceptibility for infections, especially of the mucosal system . We examined whether IgA, an important mediator of mucosal immunity, activates the complement system via the lectin pathway . Our results indicate a dose-dependent binding of MBL to polymeric, but not monomeric IgA coated in microtiter plates . This interaction involves the carbohydrate recognition domain of MBL, because it was calcium dependent and inhibited by mannose and by mAb against this domain of MBL . Binding of MBL to IgA induces complement activation, as demonstrated by a dose-dependent deposition of C4 and C3 upon addition of a complement source . The MBL concentrations required for IgA-induced C4 and C3 activation are well below the normal MBL plasma concentrations . In line with these experiments, serum from individuals having mutations in the MBL gene showed significantly less activation of C4 by IgA and mannan than serum from wild-type individuals . We conclude that MBL binding to IgA results in complement activation, which is proposed to lead to a synergistic action of MBL and IgA in antimicrobial defense . Furthermore, our results may explain glomerular complement deposition in IgA nephropathy. Phytother Res, 2001 Aug, 15(5), 437 - 40 Antimicrobial activity of seed extracts and bondenolide from Caesalpinia bonduc (L.) Roxb; Simin K et al.; The antibacterial and antifungal activities, along with a phytotoxicity test of the newly isolated diterpene bondenolide (1), of a methanol extract, ethylacetate fraction and water soluble part of the methanol extract of Caesalpinia bonduc (L.) Roxb . were assayed . Eur J Gastroenterol Hepatol, 2001 Aug, 13(8), 967 - 9 Metallic cough and pyogenic liver abscess; Ala A et al.; The curious symptom of a metallic cough in association with a pyogenic hepatic abscess should heighten awareness of a fistula . We describe a 78-year-old female with severe diverticular disease, on long-term steroid treatment for polymyalgia rheumatica . She developed a pyogenic liver abscess, treated initially by antimicrobial therapy, and subsequently drained by ultrasound and computed tomography-guided percutaneous transhepatic pigtail catheterization . This was complicated by a fistulous communication between the abscess cavity and the bronchus, confirmed by radiology . After repeated attempts at drainage and antimicrobial therapy the abscess cavity, including the hepatobronchial fistula, resolved. Braz J Infect Dis, 2001 Jun, 5(3), 124 - 9 Epub 2003 Feb 19. Treatment of nosocomial pneumonia: an experience with meropenem; Santos SS et al.; This study aimed at evaluating the efficacy and safety of meropenem as first choice treatment for nosocomial pneumonia (NP) in intensive care units (ICU) in Hospital das Clinicas (HC) - University of Sao Paulo; a hospital with high incidence of antimicrobial resistance . Prospective, open, and non-comparative trial with meropenem were done in patients with ventilator-associated or aspiration NP in 2 ICUs at HC - University of Sao Paulo . Etiologic investigation was done through bronchoalveolar lavage and blood cultures prior to study entry . Twenty-five (25) critically ill patients with NP were enrolled (mean age 40 years) . Ventilator-acquired pneumonia was responsible for 76% of cases and aspiration NP for 24% . Specific etiologic agents were identified and considered to be clinically and temporally responsible for NP in 11 (44%) patients . A . baumanii was responsible for 6 cases (55%), P . aeruginosa for 3 (27%), and S . aureus for 2 (18%) . At completion of treatment, 19 patients (76%) showed either cure (48%) or improvement (28%) after use of meropenem therapy . Mortality was 12% at the end of therapy (8% after excluding 1 non-evaluable patient) . After 4 to 6 weeks of follow-up, 12 (48%) patients had improved or been totally cured, and overall mortality was 24% . Clinical complications were observed in 11 patients (44%), with none of them definitely related to the study drug . Meropenem as monotherapy was effective and well-tolerated in most NP patients in our ICU . The low mortality rate in this study might have been due to first choice use of this drug . Controlled, drug comparative clinical trials are needed to support this preliminary observation. Am J Reprod Immunol, 2001 Aug, 46(2), 169 - 79 Comparative T-cell responses during pregnancy in large animals and humans; Meeusen EN et al.; PROBLEM: Placentation in different large animal species shows a remarkable diversity in the level of trophoblast invasion into the maternal endometrial tissues . We wish to determine the influence of implantation on T-cell responses during pregnancy . METHOD OF STUDY: Review of the literature and current data . RESULTS: alphabeta-TCR+ T cells are only prominent during early pregnancy in species with relatively non-invasive placentation (pig and horse) but are rapidly downregulated in species with more invasive placentae . gammadelta-TCR+ T cells are prominent in species with moderate trophoblast invasion (ruminants) where they increase dramatically during mid and late pregnancy . gammadelta-TCR+ T cells remain prominent during late gestation in species with highly invasive placentation (humans) and, in addition, a distinct gammadelta T-cell population is present in first trimester decidua where it may play a regulatory role in controlling natural killer cell activity . The gammadelta-TCR+ population present in both ruminants and humans shows large granular morphology and contains antimicrobial proteins, suggesting their function may be to protect the uterine environment from infection during pregnancy and parturition . CONCLUSION: The comparative analysis of T-cell responses during pregnancy in different large animal species supports an increasing role for cells of the innate immune response (NK and gammadelta T cells) and a downregulation of the adaptive immune response with increasingly invasive placentation. Arch Ital Urol Androl, 2001 Mar, 73(1), 15 - 25 {Antioxidant therapeutic efficiency after the use of carnitine in infertile patients with bacterial or non bacterial prostato-vesiculo-epididymitis}; Vicari E et al.; OBJECTIVE: In the male genital tract, reactive oxygen species (ROS) overproduction generated by infiltrating WBC or spermatozoa is one of the major causes of defective sperm function . Recently, we demonstrated that prostato-vesiculo-epididymitis (PVE) is the male accessory gland infection more crucial for the establishment of this cellular (sperm and/or WBC oxidative) response . This biochemical stress is due to an imbalance of pro and antioxidants factors and persists even after treatment with antimicrobials . Thus, the antioxidative properties of Carnitines (in terms of combined "Carnitine-Acetil-Carnitine" system) have currently found more attention as part of antimicrobial therapies . In this study, we compared which antioxidative strategy was more beneficial for the treatment of PVE . MATERIALS AND METHODS: We selected two groups of infertile patients . One group consisted of 55 abacterial PVE patients (mean age 34 yrs, range 27-40) (group A); the other included other 35 bacterial PVE patients (mean age 35 yrs, range 28-38) (group B) . Each group was randomly subdivided into the following treatment subsets: 1) A1 (n = 14) and B1 (n = 23) subsets received respectively a combined antibiotic and/or antiphlogistic regimen (x 14 days/ monthly x 3 months) (first step) followed by L-Carnitine 1 g x 2 day + acetyl-Carnitine 0.5 g x 2/day x other 3 months (second step) and finally no drug x other 3 months (third step) . 2) A2 (n = 8) and B2 (n = 16) subsets received, for a 3 month period, in the meantime the combined antibiotic and/or antiphlogistic regimen (x 14 days/monthly) and L-Carnitine 1 g x 2/day + acetyl-Carnitine 0.5 g x 2/day (first step) and finally no drug x other 3 months (second step) . 3) A3 (n = 8) and B3 (n = 12) subsets received for a 3-month period L-Carnitine 1 g x 2/day + acetyl-Carnitine 0.5 g x 2 day (first step) and finally no drug x other 3 months (second step) . Before and after each step of the therapeutical design, all patients underwent semen and quantitative bacteriological analyses and 60/90 semen specimens were also investigated about ROS production analysis by chemiluminescence in their 45% and 90% Percoll-generated fractions . RESULTS: The antioxidative response either in terms of significant decrease in the ROS production and increase in some semen parameters (sperm motility and viability) were highest in the patients of A1/B1 subsets, followed by A2/B2 subsets and lowest in the A3/B3 subsets . CONCLUSION: These results indicate that in PVE patients antimicrobials and/or antiphlogistic drugs get a full positive antimicrobial response but a partial antioxidative response, which seems to be potentiated by the addition of antioxidative agents (Carnitines) . Furthermore, it is important to underline that the antioxidative treatment with Carnitines administered in the meantime with antiinfectious agents is less effective, and finally this treatment is unsuccessful without the eradication of the pro-oxidant (germs and WBC) agents. Arzneimittelforschung, 2001, 51(7), 588 - 95 Efficacy of cetylpyridinium chloride used as oropharyngeal antiseptic; Pitten FA et al.; Cetylpyridinium chloride, (CPC, CAS 123-03-5) as active ingredient of antiseptic oral mouthrinses has a broad antimicrobial spectrum with a rapid bactericidal effect on gram-positive pathogens and a fungicide effect on yeasts in particular . There are gaps in its effectiveness against gram-negative pathogens and mycobacteria . Application of CPC at a concentration of 0.05% as a mouthrinse results in an immediate reduction in bacterial counts of 2.0 to 2.5 log steps (which is adequate to > 99%) . This reverts to about 1 log step (= 90%) 1 h after application . The ability of CPC to inhibit plaque and thereby reduce gingivitis is assured . In comparison to chlorhexidine, CPC has a lower residual effect, and as a result a lesser effect against plaque and gingivitis . The efficacy of CPC against oropharyngeal candidiasis is assured . CPC mouthrinses can significantly reduce infectious aerosols in dental practice, thereby protecting both staff and the patient . The balance of intra-oral bacterial flora is not disturbed even in the case of relatively long-term use of CPC (up to six weeks) . Taking these properties into consideration, CPC may be considered as an alternative active ingredient in the case of chlorhexidine intolerance in the treatment and prevention of bacterial or fungal disorders of the oropharyngeal cavity . It is also of interest as an element for combination in the development of new types of oropharyngeal antiseptics. Rev Belge Med Dent, 2000, 55(4), 345 - 51 {The use of glass ionomer cements in endodontics}; De Moor R et al.; Glass ionomer cements are currently used in endodontic therapy for sealing root canals (orthogradely and retrogradely), for sealing and restoring the pulp chamber, for repairing perforations and root resorption defects, and, rarely, for treating vertically fractured teeth . The successful use of these cements is the result of their particular characteristics: a chemical bond to dentin, which enhances the seal of the root canal and the reinforcement of the tooth; a good biocompatibility in the periradicular area and a fluoride release without loss of strength of the material . The fluoride release imparts an antimicrobial effect to combat root canal infection and attributes to bone mineralization after surgery . The present paper reviews the literature regarding the various applications of glass ionomer cements in present-day endodontics. Am J Physiol Lung Cell Mol Physiol, 2001 Sep, 281(3), L517 - 23 Lung surfactant and reactive oxygen-nitrogen species: antimicrobial activity and host-pathogen interactions; Hickman-Davis JM et al.; Surfactant protein (SP) A and SP-D are members of the collectin superfamily . They are widely distributed within the lung, are capable of antigen recognition, and can discern self versus nonself . SPs recognize bacteria, fungi, and viruses by binding mannose and N-acetylglucosamine residues on microbial cell walls . SP-A has been shown to stimulate the respiratory burst as well as nitric oxide synthase expression by alveolar macrophages . Although nitric oxide (NO.) is a well-recognized microbicidal product of macrophages, the mechanism(s) by which NO . contributes to host defense remains undefined . The purpose of this symposium was to present current research pertaining to the specific role of SPs and reactive oxygen-nitrogen species in innate immunity . The symposium focused on the mechanisms of NO*-mediated toxicity for bacterial, human, and animal models of SP-A- and NO.-mediated pathogen killing, microbial defense mechanisms against reactive oxygen-nitrogen species, specific examples and signaling pathways involved in the SP-A-mediated killing of pulmonary pathogens, the structure and binding of SP-A and SP-D to bacterial targets, and the immunoregulatory functions of SP-A. Bioorg Med Chem, 2001 Aug, 9(8), 2015 - 24 The synthesis and screening of 1,4,5,8-naphthalenetetracarboxylic diimide-peptide conjugates with antibacterial activity; Miller CT et al.; We have employed an initial combinatorial approach followed by systematic lead optimization to investigate a series of novel molecules that exhibit antimicrobial activity against Gram-negative and Gram-positive bacteria . The new molecules contain various sequences of amino acids, generally L-lysine and glycine, attached to the 1,4,5,8-naphthalenetetracarboxylic diimide aromatic unit . Systematic structure-activity studies found that increasing positive charge enhanced activity and molecules containing one naphthalenetetracarboxylic diimide unit as well as at least seven lysine residues were optimum for antimicrobial activity . The naphthalenetetracarboxylic diimide derivatives were found to be inactive against mammalian cell lines, making them excellent antimicrobial candidates . Our results indicate that combining positive charge with aromatic and/or hydrophobic elements may be an interesting new approach to antimicrobial agents and adds an important new dimension to the field of cationic peptides. Drug Resist Updat, 1999 Apr, 2(2), 116 - 126 Antimicrobial peptides from platelets; Yeaman MR et al.; The fact that platelets play a key role in host defense against infection has been demonstrated by the following observations(1): (a) platelets rapidly respond to sites of endovascular trauma and chemotactic stimuli associated with microbial colonization, and they are the earliest and predominant cells at sites of microbial colonization of vascular endothelium; (b) platelets have surface receptors and cytoplasmic granules comparable in structure and function to those of neutrophils, monocytes, or macrophages; (c) platelets adhere directly to, and may internalize, microbial pathogens, thereby enhancing their clearance from the bloodstream and limiting their potential for hematogenous dissemination; (d) bacterial, fungal, and protozoal pathogens are damaged or killed by activated platelets in vitro; (e) platelets are capable of initiating or amplifying complement fixation in the presence of microorganisms; (f) platelets generate oxygen metabolites which likely contribute to their antimicrobial activity; (g) platelets and leukocytes interact synergistically to exert enhanced antimicrobial functions in vitro; (h) thrombocytopenia increases susceptibility to and severity of certain infections . Importantly, rabbit and human platelets are now known to contain and release microbicidal proteins (termed platelet microbicidal proteins {PMPs} or thrombin-induced PMPs {tPMPs}) when stimulated with microorganisms or platelet agonists associated with infection in vitro . It is hypothesized that these microbicidal peptides accumulate locally at sites of endovascular damage or infection . Recent investigations have confirmed that tPMP-susceptible pathogens are less capable of proliferation or hematogenous dissemination in vivo as compared with their isogenic counterpart strains that are resistant to PMPs . Collectively, the above observations strongly suggest that platelets play key and multi-faceted roles in antimicrobial host defense which appear to be significantly mediated by PMPs and tPMPs . Mol Biotechnol, 2001 Jul, 18(3), 193 - 8 A simple method for the purification of an antimicrobial peptide in recombinant Escherichia coli; Hwang SW et al.; A magainin derivative, designated MSI-344, was produced in Escherichia coli as fusion protein, by utilizing a truncated amidophsphoribosyltransferase of E . coli as a fusion partner . Bacterial cells transformed with the gene encoding the fusion protein were grown to a high cell density and induced with isopropyl-1-thio-b-D-galatoside (IPTG) to initiate product expression . The fusion protein was accumulated into cytoplasmic inclusion body and recombinant MSI-344 was released from the fusion partner by hydroxylamine treatment . Following cleavage of the fusion protein with hydroxylamine, the released MSI-344 was purified to homogeneity by cationic exchange chromatography . The final purity was at least 95% by reversed-phase high performance liquid chromatography (RP-HPLC) . Purified recombinant MSI-344 was found to be indistinguishable from the synthetic peptide determined by amino acid sequences and antimicrobial activity assay. Antimicrob Agents Chemother, 2001 Sep, 45(9), 2604 - 8 Susceptibilities of Mycoplasma hominis, M . pneumoniae, and Ureaplasma urealyticum to GAR-936, dalfopristin, dirithromycin, evernimicin, gatifloxacin, linezolid, moxifloxacin, quinupristin-dalfopristin, and telithromycin compared to their susceptibilities to reference macrolides, tetracyclines, and quinolones; Kenny GE et al.; The susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to eight new antimicrobial agents were determined by agar dilution . M . pneumoniae was susceptible to the new glycylcycline GAR-936 at 0.12 microg/ml and evernimicin at 4 microg/ml, but it was resistant to linezolid . It was most susceptible to dirithromycin, quinupristin-dalfopristin, telithromycin, reference macrolides, and josamycin . M . hominis was susceptible to linezolid, evernimicin, and GAR-936 . It was resistant to macrolides and the ketolide telithromycin but susceptible to quinupristin-dalfopristin and josamycin . U . urealyticum was susceptible to evernimicin (8 to 16 microg/ml) and resistant to linezolid . It was less susceptible to GAR-936 (4.0 microg/ml) than to tetracycline (0.5 microg/ml) . Telithromycin and quinupristin-dalfopristin were the most active agents against ureaplasmas (0.06 microg/ml) . The new quinolone gatifloxacin was active against M . pneumoniae and M . hominis at 0.12 to 0.25 microg/ml and active against ureaplasmas at 1.0 microg/ml . The MICs of macrolides were markedly affected by pH, with an 8- to 32-fold increase in the susceptibility of M . pneumoniae as the pH increased from 6.9 to 7.8 . A similar increase in susceptibility with increasing pH was also observed with ureaplasmas . Tetracyclines showed a fourfold increase of activity as the pH decreased 1 U, whereas GAR-936 showed a fourfold decrease in activity with a decrease in pH. Pharmacotherapy, 2001 Aug, 21(8 Pt 2), 133S - 148S Antifungal pharmacodynamics: concentration-effect relationships in vitro and in vivo; Groll AH et al.; The pharmacodynamics of antifungal compounds involve relationships among drug concentrations, time, and antimicrobial effects in vitro and in vivo . Beyond better understanding of a drug's mode of action, characterization of these relationships has important implications for setting susceptibility breakpoints, establishing rational dosing regimens, and facilitating drug development . Important advances have been made in the experimental investigation of pharmacokinetics and pharmacodynamics of antifungal drugs; however, much remains to be learned about specific pathogens and specific sites of infection . Increased incorporation of pharmacokinetic and pharmacodynamic principles in experimental and clinical studies with antifungal agents is an important objective that will benefit the treatment and prophylaxis of life-threatening invasive fungal infections in immunocompromised patients. Anticancer Res, 2001 May-Jun, 21(3C), 2171 - 4 Human alpha-and beta-defensin immunoreactivity in oral mucoepidermoid carcinomas; Mizukawa N et al.; The purpose of this study was to demonstrate the immunohistochemical localization and distribution of human alpha- and beta-defensins, peptides with antimicrobial activity, in oral mucoepidermoid carcinoma tissue . Tissue samples were embedded in paraffin and alpha- and beta-defensins were immunostained by the streptavidin-biotin coupled peroxidase method . Cancer cells that constituted the ducts, as well as neutrophils, were positively immunostained with the anti-alpha-defensin antibody (HNPs) . On the other hand, epidermoid cells and intermediate cells were intensely stained with the anti-beta-defensin-2 (HBD-2) antibody . Mucous-secreting cells were clearly not immunostained with the anti-HBD-2 antibody . The epithelial hyperplasia region adjacent to the tumor tissues was also positively immunostained with the anti-HBD-2 antibody. Am J Respir Crit Care Med, 2001 Aug 1, 164(3), 382 - 8 Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study; Bergmans DC et al.; Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated . Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis . In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis {control group A} and 61 patients were studied in an intensive care unit where no topical prophylaxis was used {control group B}) . Baseline characteristics were comparable in all three groups . Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A {p < 0.00001} and 9% in control group B patients {p < 0.00001}) and in trachea (52% versus 22% in A {p = 0.03} and 7% in B {p = 0.004}) . Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A {p < 0.00001} and 63% in B {p < 0.00001}) . Colonization rates in stomach and intestine were not affected . Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively) . This was not associated with shorter durations of ventilation or ICU stay or better survival . Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention . Keywords: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects Pharmacoepidemiol Drug Saf, 2001 Mar-Apr, 10(2), 143 - 8 Minimized analysis of costs applied to antimicrobial consumption in a rural area; Sanchez CC et al.; PURPOSE: Antimicrobial agents constitute one of the most utilized groups of drugs in daily clinical practice and, therefore they involve a significant expense . The aim of this study was to evaluate the economic cost of the antimicrobials prescribed in a rural area as well as to search for some cheaper alternatives . METHODS: Retrospective study . The economic cost of antimicrobial agents prescribed at a health centre over 18 months was studied . To do this, clinical histories of 800 people were reviewed . Afterwards, a minimized analysis of costs was carried out . RESULTS: The total cost of antimicrobial consumption came to 2,080.752 pts . The average expenditure per patient came to 6,433.85 +/- 14 269.29 pts . Significant differences between the sexes were not found; however, the expenditure in patients of 65 years of age or over was significantly higher than the rest . After applying the ABC analysis it was noticed that macrolides, cephalosporins, antimicrobial combinations and quinolones were the most important groups from an economic point of view . The use of monodose containers would allow us to save up to 7.83% of the total expenditure . In addition, by prescribing the cheapest marketed pharmaceutical product we could save a further 6.54%, and, finally, by combining these two measures the total possible saving would reach 299,052 pts, a 14.37% of the total expenditure . CONCLUSION: We consider important the elaboration of pharmacoeconomic guides as well as the introduction of monodose containers not only at hospitals but also at community pharmacists. J Dent Res, 2001 Jun, 80(6), 1545 - 9 The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats; Sulkala M et al.; Previous studies suggest that salivary and pulp-derived host enzymes, matrix metalloproteinases (MMPs), may be involved in dentin caries pathogenesis . To study the inhibition of acid-activated human salivary MMPs by non-antimicrobial chemically modified tetracyclines (CMTs), we used a functional activity assay with 125I-labeled gelatin as a substrate . To address the role of MMPs in the progression of fissure caries in vivo, we administered the MMP inhibitors CMT-3 and zoledronate to young rats per os for 7 weeks, 5 days a week . Caries lesions were visualized by Schiff reagent in sagittally sectioned mandibular molars . Marked reduction in gelatinolytic activity of human salivary MMPs was observed with CMT-3 . CMT-3 and zoledronate, both alone and in combination, also reduced dentin caries progression in the rats . These results suggest that MMPs have an important role in dentin caries pathogenesis, and that MMP inhibitors may prove to be useful in the prevention of caries progression. Drug Resist Updat, 2000 Oct, 3(5), 265 - 269 Infectious disease 2000: drug resistance and new drugs; Georgopapadakou NH; 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was held in Toronto on 17-20 September 2000 . It attracted thousands of delegates from industry and academia and covered, in over 2300 oral and poster presentations, topics ranging from microbial pathogenesis to infection control, vaccines, antibiotic resistance and new antimicrobial agents . Summarized here are highlights on microbial resistance and agents in clinical and preclinical development . Mol Plant Microbe Interact, 2001 Aug, 14(8), 947 - 54 Maize rhm1 resistance to Bipolaris maydis is associated with few differences in pathogenesis-related proteins and global mRNA profiles; Simmons CR et al.; The maize rhm1 mutant resists Bipolaris maydis, the causal agent of Southern corn leaf blight, by producing small necrotic lesions surrounded by chlorotic haloes . The rhm1 and wild-type lesions contain viable fungus in equal frequency, but fungal sporulation was markedly inhibited on rhm1 . The levels of the pathogenesis-related (PR) proteins chitinase, PR1, and peroxidase differ little between rhm1 and wild type, with or without B . maydis inoculation . The global mRNA profiles surveyed revealed hundreds of cDNA fragments that were twofold or more induced or suppressed in rhm1 and wild-type plants following B . maydis inoculation . Nonetheless, between rhm1 and wild type, only 0.4 to 0.7% of the cDNA fragments were expressed differentially by twofold or more . Among the up-regulated genes in rhm1 was beta-glucosidase glu1, which prompted a test of whether rhm1 resistance depends upon the antimicrobial compound 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one or other hydroxamic acids whose glucosyl conjugates are preferred substrates for the Glu1 enzyme . Double mutants of rhm1 and bx1, a hydroxamic acid-deficient mutant, indicate that rhm1 resistance is hydroxamic acid independent . The rhm1 resistance presently appears to operate via a mechanism unlike those of previously described resistance genes. Support Care Cancer, 2001 Jul, 9(5), 372 - 9 Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients; Fleischhack G et al.; The beta-lactam/beta-lactamase inhibitor combinations are a good choice for empirical antimicrobial therapy in febrile neutropenic patients, because their antibacterial spectra include both gram-negative and gram-positive pathogens . This trial was initiated to assess the efficacy and safety of piperacillin with the beta-lactam inhibitors sulbactam (PSG group) or tazobactam (PTG group) and gentamicin as initial therapy in febrile neutropenia of pediatric patients . In a prospective study, 239 episodes of fever and neutropenia were analyzed for the clinical and microbiological response dependent on infection etiology and treatment group: 66.5% of episodes were classified as fever of unknown origin (FUO) and 33.5%, as microbiologically or clinically documented infections; 19.2% of all episodes were due to bacteremia, predominantly caused by gram-positive organisms (69.6%) . The response to the initial therapy was 55.2% overall and 65.4% in episodes of FUO with a significant higher success rate in the PSG group than in the PTG group (70.1% vs . 52.4%, P=0.039), and 35.0% in documented infections . In episodes with documented infection longer duration of fever and antimicrobial therapy was recorded than for FUO episodes . Four patients died of causes related to infection . Fever relapse occurred in 26 episodes (11.1%), predominantly in patients who were still neutropenic . Toxic side effects were minimal . The initial therapy of piperacillin with sulbactam or tazobactam in combination with gentamicin is well tolerated, and its efficacy is comparable to that of other combination therapies or of monotherapy with beta-lactam antibiotics in pediatric neutropenic cancer patients. Cell Mol Life Sci, 2001 Jun, 58(7), 978 - 89 The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity; Yang D et al.; Since we live in a dirty environment, we have developed many host defenses to contend with microorganisms . The epithelial lining of our skin, gastrointestinal tract and bronchial tree produces a number of antibacterial peptides, and our phagocytic neutrophils rapidly ingest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicrobial activities . Some of these antimicrobial moieties also appear to alert host cells involved in both innate host defense and adaptive immune responses . The epithelial cells are a source of constitutively produced beta defensin (HBD1) and proinflammatory cytokine-inducible beta defensins (HBD2 and -3) and cathelicidin (LL37) . The neutrophils-derived antimicrobial peptides are released on demand from their cytoplasmic granules . They include the enzymes cathepsin G and chymase, azurocidin, a defensins and cathelicidin . In contrast, C5a and C3b are produced by activation of the serum complement cascade . The antimicrobial moieties direct the migration and activate target cells by interacting with selected G-protein-coupled seven-transmembrane receptors (GPCRs) on cell surfaces . The beta defensins interact with the CCR6 chemokine GPCRs, whereas cathelicidins interact with the low-affinity FPRL-1 receptors . The neutrophil-derived cathepsin G acts on the high-affinity FMLP receptor (GPCR) known as FPR, while the receptors for chymase and azurocidin have not been identified as yet . The serum-derived C5a uses a GPCR known as C5aR to mediate its chemotactic and cell-activating effects . Consequently, all these ligand-receptor interactions in addition to mediating chemotaxis also activate receptor-expressing cells to produce other mediators of inflammation. J Am Vet Med Assoc, 2001 Aug 1, 219(3), 341 - 5 Osteomyelitis of the sustentaculum tali in horses: 10 cases (1992-1998); Hand DR et al.; OBJECTIVE: To determine outcome of horses with osteomyelitis of the sustentaculum tali (ST), with or without associated tarsal sheath tenosynovitis, following surgical debridement and lavage . DESIGN: Retrospective study . ANIMALS: 10 horses in which a diagnosis of osteomyelitis of the ST had been made on the basis of history, physical examination findings, and results of radiography . PROCEDURE: Information on results of diagnostic testing, surgical findings, postoperative treatment, and short-term outcome was obtained from the medical records . Long-term follow-up information was obtained through reevaluation of horses at the teaching hospital and telephone conversations with referring veterinarians, owners, and trainers . RESULTS: Treatment consisted of surgical debridement, intra- and postoperative lavage, and long-term antimicrobial and anti-inflammatory treatment . Eight horses had evidence of involvement of the tarsal sheath . One horse was euthanatized after surgery because of a lack of response to treatment; the other 9 were discharged from the hospital . Severity of lameness had improved, but all still had grade-1 or -2 lameness at the time of discharge . One horse was euthanatized after discharge because of contralateral hind limb laminitis, and another horse was lost to follow-up . Of the remaining 7 horses, 6 returned to their previous use, and 1 was sound but retired for breeding for unrelated reasons . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that horses with osteomyelitis of the ST, with or without concomitant tarsal sheath tenosynovitis, can have an excellent to good outcome and may return to their previous use after surgical debridement of affected tissues and lavage of the tarsal sheath. J Am Vet Med Assoc, 2001 Aug 1, 219(3), 334 - 7 Owner survey of headshaking in horses; Madigan JE et al.; OBJECTIVE: To determine signalment, history, clinical signs, duration, seasonality, and response to various treatments reported by owners for headshaking in horses . DESIGN: Owner survey . ANIMALS: 109 horses with headshaking . PROCEDURE: Owners of affected horses completed a survey questionnaire . RESULTS: 78 affected horses were geldings, 29 were mares, and 2 were stallions . Mean age of onset was 9 years . Headshaking in 64 horses had a seasonal component, and for most horses, headshaking began in spring and ceased in late summer or fall . The most common clinical signs were shaking the head in a vertical plane, acting like an insect was flying up the nostril, snorting excessively, rubbing the muzzle on objects, having an anxious expression while headshaking, worsening of clinical signs with exposure to sunlight, and improvement of clinical signs at night . Treatment with antihistamines, nonsteroidal anti-inflammatory drugs, corticosteroids, antimicrobials, fly control, chiropractic, and acupuncture had limited success . Sixty-one horses had been treated with cyproheptadine; 43 had moderate to substantial improvement . CONCLUSIONS AND CLINICAL RELEVANCE: Headshaking may have many causes . A large subset of horses have similar clinical signs including shaking the head in a vertical plane, acting as if an insect were flying up the nostrils, and rubbing the muzzle on objects . Seasonality and worsening of clinical signs with exposure to light are also common features of this syndrome . Geldings and Thoroughbreds appear to be overrepresented . Cyproheptadine treatment was beneficial in more than two thirds of treated horses. Pharm Res, 2001 Jul, 18(7), 937 - 42 The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs; Adriaens E et al.; PURPOSE: The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism . METHODS: The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment . Additionally, mucus production and reduction in body weight of the slugs were measured . The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay . The antimicrobial activity of the different BAC analogues was also assessed . RESULTS: All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 < BAC-C14 < BAC-C12 approximately BAC-mix . A similar ranking was obtained with the BCOP assay for eye irritation . The relative order of activities among the three BAC analogues was the same, i.e., BAC-C14 > or = BAC-C16 > BAC-C12 . The BAC-C14 exhibited higher activity than the BAC-mix . CONCLUSIONS: The toxicity and activity of BAC analogues depend on the alkyl chain length . The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered. Vestn Khir Im I I Grek, 2001, 160(2), 39 - 45 {Local application of low-energy aerial and argon plasma in the treatment of suppurative wounds and trophic ulcers}; Khrupkin VI et al.; The authors describe experimental and clinical (113 patients) data demonstrating the antimicrobial, hemostatic and stimulating the regenerating processes property of the low energy plasma in local treatment of purulent and long-standing wounds and trophic ulcers. Am J Health Syst Pharm, 2001 Aug 1, 58(15), 1406 - 12 Potential risks and prevention, Part 4: Reports of significant adverse drug events; Kelly WN; A summary analysis of three descriptive studies of significant adverse drug events (ADEs) was conducted . Case reports of ADEs published in Clin-Alert during 1976-97 were the source of information on ADEs, including drug-induced deaths, disabilities, and threats to life . The results of the three studies were compared, and recommendations were made . During the 21-year period, 1520 significant ADEs were reported (29% resulting in death, 15% in permanent disability, and 56% in life threats) . Event types were distributed as adverse drug reactions (52%), allergic drug reactions (25%), medication errors (15%), and drug interactions (8%) . Only 12% of the drug interactions were classified as having highest significance by one drug information reference, while 32% of the drug interactions were unclassified . Typically, patients were 40-69 years old and relatively healthy or only moderately ill and had received usual dosages . However, 29% of the patients with a drug-induced permanent disability were less than 10 years old . Only 17% of the drugs that could have been monitored by blood level tests were so monitored . The drug categories most commonly involved in ADEs were central-nervous-system agents, antimicrobials, antineoplastics, and cardiovascular agents . The nervous, hematopoietic, cardiovascular, and respiratory systems were affected the most . Faulty prescribing was the most common reason for medication error, and wrong dosage was the most common type of error . A lawsuit was reported in 13% of the cases . Overall, 52% of the cases were judged to have been preventable; of these, 50% could have been prevented by a pharmacist . Litigation was reported for 13% of the cases; settlements and judgments averaged $3.1 million . A summary analysis of more than 1500 published case reports of ADEs for 1976-97 yielded information on possible risk factors for drug-related deaths, disabilities, and life threats and on which events may have been preventable. Am J Health Syst Pharm, 2001 Aug 1, 58(15), 1399 - 405 Potential risks and prevention, Part 3: Drug-induced threats to life; Marcellino K et al.; Potential risk factors for and the preventability of drug-induced threats to life were studied . Case reports of adverse drug events (ADEs) published in Clin-Alert during 1977-97 were the source of information on drug-induced life threats . Patient, drug, and event variables were identified, and the causality, predictability, and preventability of each case were assessed . Data were entered into a relational database for analysis . The data indicated 846 drug-induced life threats . Seventy-four percent of the cases were assessed as definite or probable . Patients received usual or below-usual dosages in 89% of the cases . Patients tended to be middle-aged and only moderately ill . The drug categories most frequently associated with life threats were antimicrobials and central-nervous-system agents . Plasma drug level monitoring should have been performed in 127 cases but occurred only in 31 cases (24%) . Event types were distributed as adverse drug reactions (50%), allergic reactions (35%), drug interactions (11%), and medication errors (4%) . A commercial reference classified almost half of the drug interactions associated with a life threat as posing minimal or no potential risk to the patient . Half of the life-threatening events were judged to have been preventable; about half of these could have been prevented by a pharmacist . Litigation was reported for only 1% of the cases of drug-induced threats to life; judgments and settlements averaged $1.2 million . A review of published case reports of ADEs for 1977-97 yielded information on possible risk factors for drug-induced life threats and on which events may have been preventable. Rev Argent Microbiol, 2001 Apr-Jun, 33(2), 113 - 7 {Determination of the antibacterial and antiviral activity of the essential oil from Minthostachys verticillata (Griseb.) Epling}; Primo V et al.; The in vitro antiviral activity of the essential oil from Minthostachys verticillata was investigated against herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PrV) . The viral inhibition was assayed employing viral plaque reduction assay . The antiviral activity of the essential oil specifically affects PrV and HSV-1 multiplication, since it was found that non toxic effects on cells were observed at the concentrations assayed . The therapeutic index values were 10.0 and 9.5 for HSV-1 and PrV, respectively . The antibacterial activity was studied using a diffusion assay and the broth tube dilution method . Gram-positive bacteria were more sensitive to inhibition by plant essential oil than the gram-negative bacteria . The essential oil of M . verticillata was analyzed by gas chromatography (GC) technique . Of the six components identified in the volatile oil, pulegone (44.56%) and menthone (39.51%) were the major constituents . The antimicrobial activity can be explained to some extent by the presence of pulegone . Results suggest that further investigations concerning the isolation of the substance responsible for the antimicrobial activity and an effort to define the mechanisms of action are warranted. J Clin Periodontol, 2001 Sep, 28(9), 833 - 9 Systemic and local antimicrobial use in periodontal therapy in England and Wales; Choudhury M et al.; BACKGROUND/AIMS: The aim of this study was to investigate antimicrobial use during periodontal therapy in dental practice in England & Wales . METHOD: This was a postal questionnaire survey of 800 dentists, 400 general dental practitioners (GDP) in National Health Service practice and 400 members of the British Society of Periodontology (Periodontal Society) primarily in dental practice . We designed and piloted a questionnaire to evaluate both systemic and local antibiotic use with periodontal therapy as well as factors affecting their prescription . In addition, we also investigated the potential use of antibiotic sensitivity testing, since this has been recommended prior to prescribing antibiotics . Two follow-up mailings were used to encourage non-responders . RESULTS: The useable return rate for the questionnaires was 587/800 (73%) . Systemic antibiotics were used by 7.4% Periodontal Society members and 18.4% GDP for untreated adult periodontitis patients (p<0.001) . Antimicrobials were prescribed more frequently by Periodontal Society members in early onset (52.7%) and refractory periodontitis patients (49.6%), and this was highly statistically significantly greater usage than GDP (p<0.001) . Regarding local antimicrobials, usage for untreated adult periodontitis was Periodontal Society 8.9% and GDP 5.4% . Higher usage of local antimicrobials was found both for the treatment of recurrent pocketing in adult periodontitis (Periodontal Society 26.3%, GDP 14.8%, p<0.014) and refractory periodontitis (Periodontal Society 30.8%, GDP 15.2%, p<0.001) . As reasons for using local antimicrobials, more than 80% of all respondents stated superiority over root debridement alone . Barriers to use included cost, no perceived need and lack of supporting research data . The percentage of responders considering diagnostic microbiology either theoretically or at a cost of pound 60 were by group, Periodontal Society 83% & 70.4% and GDP 76% & 51.2% . 33% of Periodontal Society members and 3.8% of GDP spent at least 45 min per quadrant on root planing and Periodontal Society members had a greater exposure to lectures on both systemic and local drug therapy compared with GDP (p<0.001) . CONCLUSIONS: Systemic antimicrobial use was infrequent for adult periodontitis and generally in line with current recommendations for other disease types . Whilst local antimicrobial therapy for periodontitis was not widespread, a substantial minority of dentists use this form of therapy and most believe that it is more effective than root debridement alone. Aust Vet J, 2001 Jun, 79(6), 398 - 402 Thoracic actinomycosis (arcanobacteriosis) or nocardiosis causing thoracic pyogranuloma formation in three dogs; Sivacolundhu RK et al.; OBJECTIVE: To describe three cases of canine thoracic actinomycosis (arcanobacteriosis) or nocardiosis in which the primary pathological lesion was a pyogranulomatous abscess in the mediastinum . Clinical signs, difficulties in diagnosis, treatment and prognosis are examined . Comparisons are made between human and veterinary literature to assist in formulating a rational treatment plan . DESIGN: Retrospective clinical study . PROCEDURE: Review of case records from 1984 to 1998 . RESULTS: Three dogs presented with large intrathoracic pyogranulomas producing variable clinical signs, not necessarily associated with the respiratory tract . Ages ranged from 2 to 5 years old . Two dogs responded to surgical opening and passive drainage of the abscess, or surgical excision of the granuloma with associated structures, and medical therapy . One dog died intra-operatively . CONCLUSION: A combination of surgical and antimicrobial therapy may carry a fair-to-good prognosis for thoracic granuloma caused by actinomycosis (arcanobacteriosis) or nocardiosis . The extent of surgery should be based on assessment of individual cases and must include surgical biopsy for histology and culture to enable a specific diagnosis to be made . Complete surgical excision is not necessarily required . Prolonged antimicrobial therapy is indicated. Gerontology, 2001 Sep-Oct, 47(5), 246 - 53 Salivary concentration of secretory leukocyte protease inhibitor, an antimicrobial protein, is decreased with advanced age; Shugars DC et al.; BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) exhibits antimicrobial activities that, in addition to other well-characterized proteins such as lysozyme and lactoferrin, is thought to play a critical role in mucosal defenses . Although elderly individuals are particularly susceptible to mucosal infections, salivary production of SLPI has not been assessed in an aged cohort . OBJECTIVES: Hypothesizing that oral SLPI concentrations are reduced with advanced age, this cross-sectional study compared SLPI concentrations to concentrations of lysozyme, lactoferrin and total protein in unstimulated salivary secretions of healthy, community-dwelling 79+-year-old and younger adults . METHODS: Study participants were 45 non-hospitalized dentate adults aged 79-89 (23 elderly) or 21-51 years (22 non-elderly) . Home-based interviews and clinical examinations determined dentate status and confirmed the absence of dentures, oral mucosal disease, anti-infective medication use, irradiation therapy for head and neck cancer and self-perceived xerostomia . Whole unstimulated saliva was collected from all subjects and analyzed for antimicrobial protein concentration by enzyme-linked immunosorbent assay and for total protein content by the bicinchoninic acid method . Bivariate and multivariate (generalized linear modeling) analyses evaluated the relationships between age, gender and salivary protein concentrations . RESULTS: Mean salivary levels of SLPI and lysozyme were lower in elderly compared with non-elderly subjects (p < 0.001), unlike lactoferrin and total protein levels . Similar results were obtained when concentrations of the individual proteins were normalized to the total protein concentration, suggesting that glandular production of SLPI and lysozyme preferentially decreases with aging . Gender differences were detected only for SLPI concentrations; males had lower SLPI levels than females regardless of age (p < 0.01) . Generalized linear models confirmed that age (p < 0.001) and gender (p < 0.05) were each associated with the SLPI concentration and together accounted for 50% of the variation in SLPI concentration in this population . CONCLUSION: These findings indicate that SLPI production is diminished among healthy community-dwelling older adults, particularly elderly males . Further investigation should determine the impact of decreased local SLPI production on the increased risk of oral mucosal disease with advanced age . Eur J Biochem, 2001 Aug, 268(15), 4278 - 84 Crumpled structure of the custom hydrophobic lytic peptide cecropin B3; Srisailam S et al.; The solution structure of a custom lytic peptide, cecropin B3 (CB3), having two identical hydrophobic segments on both the N- and C-termini, was investigated by two-dimensional NMR spectroscopy . The need to determine the structure of this peptide is rooted in its specific ability to lyse lipid layers that have a high content of anionic lipid . The lytic activities of CB3 on cell membranes including cancer cells and bacteria is found to be less than cecropin B1 . The results show that CB3 has four discrete segments forming alpha helical structures . The crumpled structure of CB3 provides evidence for the lysis of the lipid layer being via a pathway that differs from pore formation . The results in this study provide strong clues towards a rational design for a potent antimicrobial and antitumor peptide. Arch Biochem Biophys, 2001 Aug 15, 392(2), 180 - 91 Potential involvement of several nitroreductases in metronidazole resistance in Helicobacter pylori; Jorgensen MA et al.; Susceptibility of Helicobacter pylori to the antibiotic metronidazole has been attributed to the activity of an oxygen-insensitive NADPH-dependent nitroreductase (RdxA), with resistance to this antimicrobial arising from null mutations in rdxA . To obtain a better understanding of the factors involved in resistance, nitroreductase and metronidazole reduction activities were investigated in matched pairs of clinical and laboratory-derived sensitive and resistant H . pylori strains . Significant differences in enzyme activities were observed between sensitive and resistant strains, suggesting that metronidazole susceptibility in H . pylori was associated with more than one enzyme activity . To establish the mutations occurring in rdxA, the genes from seventeen bacterial strains, including matched pairs were sequenced . To assess whether metronidazole was responsible for inducing random mutations in this gene, the complete nucleotide sequence of gene hp0630, encoding an NAD(P)H-quinone reductase which also has NADPH-dependent nitroreductase activity, was determined in the same strains . All resistant strains showed nonsense, missense, or frameshift mutations randomly throughout rdxA . In contrast, no mutations were observed in hp0630 . The results confirmed the presence of rdxA null mutations in resistant strains and suggested that other factors involved in the metabolism of metronidazole contributed to the resistant phenotype . Ear Nose Throat J, 2001 Jun, 80(6 Suppl), 4 - 7 Post-tympanostomy tube otorrhea; Myer CM 3rd; Post-tympanostomy tube otorrhea is a common problem that is treated by both primary care physicians and otolaryngologists . Physicians should take a logical approach to managing this condition in order to prevent the development of antimicrobial resistance and to minimize healthcare expenditures . Once the diagnosis has been made, first-line therapy with fluoroquinolone drops, with or without suctioning, is preferred . If the condition does not resolve after a few days, suctioning is recommended and oral antimicrobial therapy can be initiated, depending on the clinical situation . Parenteral therapy is sometimes necessary for those very few patients who do not improve with oral and topical antimicrobial therapy and aggressive local care . The use of prophylactic drug therapy is controversial. Boll Chim Farm, 2001 May-Jun, 140(3), 149 - 54 Synthesis of some pyridone derivatives; Dawood NT et al.; Chlorination of 6-aryl-3-cyano-2-pyridone-4-carboxylic acid (1) afforded the corresponding acid chloride (2) and the 2-chloro derivative (3) . Esterification of (2) gave the corresponding esters (4a; b) . Hydrazinolysis of (4a) afforded the respective pyridazinone derivative (5) . Treatment of 6-aryl-2-chloro-3-cyano-4-pyridine carboxylic acid (3) with acetyl hydrazine, gave the triazinopyridine derivative (6), while treatment of 3 with sodium azide in DMF afforded the tetrazinopyridine derivative (7) . Treatment of the N-acetyl derivative (1b) with thiosemicarbazide and/or hydroxylamine hydrochloride, yielded the correspoding semicarbazone and oxine derivatives (8) and (10), respectively . The reaction of 6-aryl-3-cyano-1,2-dihydro-2-thioxo-4-pyridinecarboxylic acid (1c) with ethylchloro acetate and/or thiourea yielded the mercapto ester derivative (11) and the corresponding pyrido {2,3-d} pyrimidine thione derivative (12) . Condensation reaction of (1d) with anthranilic acid, afforded the quinazolone derivative (11) . The reactivity of 11 towards hydrazine hydrate was investigated . The structural assignment of the new derivatives were based on IR, 1H NMR and mass data . Some of the new compounds were screened, in vitro, for antimicrobial activity and the results were encouraging. Boll Chim Farm, 2001 May-Jun, 140(3), 129 - 39 Simple synthesis of condensed pyran containing compounds and their antimicrobial properties; Mishriky N et al.; Reaction of various fused pyran compounds with formic acid was studied . Thus, refluxing 6-aminopyrano{2,3-c}pyrazole-5-carbonitriles 3 with formic acid afforded the corresponding 3-aryl-3-(5-hydroxy-3-methyl-1H-pyrazole-4-yl)propanoic acids 4 . Whereas, reaction of formic acid with 2-amino-4H-1-benzopyran-3-carbonitriles 6 gave the corresponding quinoline-2,5(1H,6H)-diones 7 . The study was also extended towards many spiro compounds possessing pyran residue . The antimicrobial properties of the prepared compounds was screened. Clin Infect Dis, 2001 Sep 1, 33 Suppl 2, S94 - 106 New developments in diagnosis and treatment of infection in orthopedic implants; Widmer AF; Orthopedic implants have revolutionized treatment of bone fractures and noninfectious joint arthritis . Today, the risk for orthopedic device-related infection (ODRI) is <1%-2% . However, the absolute number of patients with infection continuously increases as the number of patients requiring such implants grows . Treatment of ODRIs most frequently includes long-term antimicrobial treatment and removal of the implant . Recent evidence from observational trials and 1 randomized clinical trial indicate that a subset of patients can be successfully treated with retention of the implant . Patients eligible for such a treatment must meet the following criteria: acute infection defined as signs and symptoms lasting <14-28 days, an unambiguous diagnosis based on histopathology and microbiology, a stable implant, and susceptibility of the microorganism to an effective orally available antimicrobial agent. Clin Infect Dis, 2001 Sep 1, 33 Suppl 2, S78 - 83 Maximizing appropriate antibiotic prophylaxis for surgical patients: an update from LDS Hospital, Salt Lake City; Burke JP; Errors in antimicrobial prophylaxis for surgical patients remain one of the most frequent types of medication errors in hospitals . Failure to administer the first dose of antimicrobial prophylaxis within the 2-h window of time before incision is associated with 2- to 6-fold increases in rates of surgical site infection . Optimal use of antimicrobial prophylaxis includes proper case selection; use of appropriate agents; proper dosing, route of administration, timing, and duration; and intraoperative dosing when appropriate . Effective use of antimicrobial prophylaxis also requires monitoring of and feedback on patterns of use . Programs to improve antimicrobial prophylaxis should be multidisciplinary and should aim to improve use of medications, not simply to change physician practice patterns . The LDS Hospital experience demonstrates the clinical and financial benefits of such a program and also shows the pitfalls of and great difficulties associated with changing systems of care. Am J Infect Control, 2001 Aug, 29(4), 275 - 80 Descriptive study of nosocomial infections in a short-term inpatient behavioral health setting; Shandera TJ; BACKGROUND: Surveillance methods for nosocomial infections, with the use of a sound epidemiologic foundation, have not been published for behavioral healthcare settings . METHODS: Nosocomial infection rates in a behavioral health care setting were quantified by integrating the following: (1) rounds/review of selected charts, (2) microbiology reports, and (3) records of antimicrobials dispensed . Incidence density rates were calculated with 1000 patient-days as the denominator . RESULTS: The incidence of nosocomial infections of all types among all patients was 3.9 infections per 1000 patient-days . Rates among specific groups of behavioral patients ranged from children (6.4 infections per 1000 patient-days) to adults (3.9 infections per 1000 patient-days) to adolescents (3.2 infections per 1000 patient-days) . Adult substance-abuse patients had a rate of 1.9 infections per 1000 patient-days . The most frequently diagnosed nosocomial infection among adult substance-abuse and behavioral patients was bronchitis at 0.5 and 0.6 infections per 1000 patient-days, respectively . The most frequently diagnosed nosocomial infection among adolescents and children was cellulitis at 0.6 and 1.3 infections per 1000 patient-days, respectively . Female patients experienced significantly more nosocomial infections than male patients, except among adult substance-abuse patients . Nosocomial infections usually occurred in patients who were hospitalized longer than the average length of stay, except among children . CONCLUSION: Nosocomial infections occur in behavioral health settings . Surveillance methods, with a sound epidemiologic foundation, must be developed. J Biol Chem, 2001 Oct 19, 276(42), 39021 - 6 Epub 2001 Aug 02. The structure of human beta-defensin-1: new insights into structural properties of beta-defensins; Hoover DM et al.; Defensins are a class of small cationic peptides found in higher organisms that serve as both antimicrobial and cell signaling molecules . The exact mechanism of the antimicrobial activity of defensins is not known, but two models have been postulated, one involving pore formation and the other involving nonspecific electrostatic interaction with the bacterial membrane . Here we report the high resolution structures of human beta-defensin-1 (hBD1) in two crystallographic space groups . The structure of a single molecule is very similar to that of human beta-defensin-2 (hBD2), confirming the presence of an N-terminal alpha-helix . However, while the packing of hBD1 is conserved across both space groups, there is no evidence for any larger quaternary structure similar to octameric hBD2 . Furthermore, the topology of hBD1 dimers that are formed between monomers in the asymmetric unit is distinct from both hBD2 and other mammalian alpha-defensins . The structures of hBD1 and hBD2 provide a first step toward understanding the structural basis of antimicrobial and chemotactic properties of human beta-defensins. Genes Dev, 2001 Aug 1, 15(15), 1900 - 12 Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-kappaB-dependent innate immune responses; Vidal S et al.; In mammals, TAK1, a MAPKKK kinase, is implicated in multiple signaling processes, including the regulation of NF-kappaB activity via the IL1-R/TLR pathways . TAK1 function has largely been studied in cultured cells, and its in vivo function is not fully understood . We have isolated null mutations in the Drosophila dTAK1 gene that encodes dTAK1, a homolog of TAK1 . dTAK1 mutant flies are viable and fertile, but they do not produce antibacterial peptides and are highly susceptible to Gram-negative bacterial infection . This phenotype is similar to the phenotypes generated by mutations in components of the Drosophila Imd pathway . Our genetic studies also indicate that dTAK1 functions downstream of the Imd protein and upstream of the IKK complex in the Imd pathway that controls the Rel/NF-kappaB like transactivator Relish . In addition, our epistatic analysis places the caspase, Dredd, downstream of the IKK complex, which supports the idea that Relish is processed and activated by a caspase activity . Our genetic demonstration of dTAK1's role in the regulation of Drosophila antimicrobial peptide gene expression suggests an evolutionary conserved role for TAK1 in the activation of Rel/NF-kappaB-mediated host defense reactions. Hum Gene Ther, 2001 Jul 20, 12(11), 1395 - 406 Regulation of adenovirus-mediated elafin transgene expression by bacterial lipopolysaccharide; Simpson AJ et al.; Lipopolysaccharide (LPS) is a mediator of inflammatory lung injury . Selective augmentation of host defense molecules such as elafin (an elastase inhibitor with antimicrobial activity) at the onset of pulmonary inflammation is an attractive potential therapeutic strategy . The aim of this study was to determine whether elafin expression could be induced by LPS administered after transfection with adenovirus (Ad) encoding human elafin downstream of the murine cytomegalovirus (CMV) promoter (known to be potentially responsive to LPS) . In addition, we aimed to determine the effect of local elafin augmentation on neutrophil migration to the lung . LPS significantly up-regulated elafin expression from pulmonary epithelial cells transfected with Ad-elafin in vitro . In murine airways expression of human elafin was achieved using doses low enough (3 x 10(7) plaque forming units) to circumvent overt vector-induced inflammation . LPS significantly up-regulated human elafin secretion in murine airways treated with Ad-elafin {117 ng/ml in bronchoalveolar lavage fluid (BALF) after LPS administration, 5.9 ng/ml after PBS, p < 0.01)} . Over-expression of elafin significantly augmented LPS-mediated neutrophil migration into the airways in vivo (1.30 x 10(6) neutrophils in BALF after Ad-elafin/LPS treatment, 0.54 x 10(6) after Ad-lacZ/LPS (p < 0.05), 0.63 x 10(6) after PBS/LPS (p < 0.05)) and significantly enhanced human neutrophil migration in vitro . These data suggest novel functions for elafin in neutrophil migration, and that judicious selection of promoters may allow single, low-dose adenoviral administration to effect inflammation-specific expression of potentially therapeutic transgenes. AIDS Res Hum Retroviruses, 2001 Jul 20, 17(11), 1041 - 5 Differential pattern in circulating nitrogen derivatives, lactoferrin, and anti-lactoferrin antibodies in HIV type 1 and HIV type 2 infections; Dapsanse V et al.; HIV-1 infection is associated with a dramatic reduction in antioxidative molecules both at the cellular level and in the circulation . This is particularly so for lactoferrin, an iron-binding protein involved in natural defenses (antimicrobial and antiviral activities, etc.) and found in whole secretions, including milk and mucus . In addition to its ability to chelate iron ions, lactoferrin inhibits hydroxy radical formation and interacts with nitric oxide (NO) . Levels of plasma lactoferrin decreased in HIV-1-infected patients in correlation with progression of the disease, and highly specific anti-lactoferrin autoantibodies increased . This profile was specific to HIV-1 infection; it was not found in HIV-2-infected patients . In parallel with the drop in lactoferrin, a marked increase in circulating nitrogen derivatives was observed in HIV-1-infected patients, whereas low levels were found in normal donors and in HIV-2-infected patients . These data suggested hyperstimulation of the NO pathway throughout HIV-1 but not HIV-2 infection . This overproduction of NO could play an important role in the development of AIDS symptoms and signs. Pharm Dev Technol, 2001 Aug, 6(3), 431 - 40 Sorption of parabens by flexible tubings; Bahal SM et al.; Flexible tubings are extensively used in pharmaceuticals, food industry, and in hospitals . This study was undertaken to compare various flexible tubings to determine their sorption characteristics, using methyl and propyl parabens . After 24 h, some tubings showed 100% sorption of propylparaben and over 40% for methylparaben . Significant losses were observed within a few hours using several tubings . For methylparaben, the losses were in the following decreasing order of sorption: Tygon, Clearflo, silicone, Nylotube, and Newtex . For propylparaben, the losses were in the following order: Tygon, Clearflo, silicone, Newtex, and Nylotube . Teflon, Zelite, and Vitube showed little to no losses of methyl and propylparaben over 120 h of study . The silicone tubing, refilled after 120 h with fresh methylparaben or propylparaben solutions, again showed significant losses within a few hours . The tubings show slow desorption when filled with the buffer vehicle . For Silastic tubing, increase in temperature from 25 to 40 degrees C, increase in pH from 3.5 to 6.5, tubing lot to lot variation, or curing with peroxide or platinum had little or no effect on paraben sorption . As expected, the sorption of parabens increased with increasing surface area of Silastic tubing . Results provided can be used to select the best tubings and to minimize paraben losses during production and filling of liquid pharmaceuticals andfood products containing these antimicrobial preservatives. J Biol Chem, 2001 Oct 5, 276(40), 37199 - 205 Epub 2001 Aug 01. Oxazolidinones mechanism of action: inhibition of the first peptide bond formation; Patel U et al.; Oxazolidinones are potent inhibitors of bacterial protein biosynthesis . Previous studies have demonstrated that this new class of antimicrobial agent blocks translation by inhibiting initiation complex formation, while post-initiation translation by polysomes and poly(U)-dependent translation is not a target for these compounds . We found that oxazolidinones inhibit trans