Int Microbiol, 2002 Dec, 5(4), 169 - 75 Epub 2002 Aug 13. Plant-microbe interactions and the new biotechnological methods of plant disease control; Montesinos E et al.; Plants constitute an excellent ecosystem for microorganisms . The environmental conditions offered differ considerably between the highly variable aerial plant part and the more stable root system . Microbes interact with plant tissues and cells with different degrees of dependence . The most interesting from the microbial ecology point of view, however, are specific interactions developed by plant-beneficial (either non-symbiotic or symbiotic) and pathogenic microorganisms . Plants, like humans and other animals, also become sick, but they have evolved a sophisticated defense response against microbes, based on a combination of constitutive and inducible responses which can be localized or spread throughout plant organs and tissues . The response is mediated by several messenger molecules that activate pathogen-responsive genes coding for enzymes or antimicrobial compounds, and produces less sophisticated and specific compounds than immunoglobulins in animals . However, the response specifically detects intracellularly a type of protein of the pathogen based on a gene-for-gene interaction recognition system, triggering a biochemical attack and programmed cell death . Several implications for the management of plant diseases are derived from knowledge of the basis of the specificity of plant-bacteria interactions . New biotechnological products are currently being developed based on stimulation of the plant defense response, and on the use of plant-beneficial bacteria for biological control of plant diseases (biopesticides) and for plant growth promotion (biofertilizers). J Immunol, 2003 Jan 1, 170(1), 575 - 80 By IL-1 signaling, monocyte-derived cells dramatically enhance the epidermal antimicrobial response to lipopolysaccharide; Liu L et al.; Epithelia react to microbial pathogens by mounting a defensive response that includes the production of antimicrobial peptides . In this study, we show that, in human epidermal cultures, Escherichia coli LPS was a very weak direct inducer of human beta-defensin (HBD)-2 mRNA and peptide, but the induction was greatly amplified when monocyte-derived cells (MoDeC) acted as intermediaries between LPS and the epidermis . IL-1R antagonist largely reversed the effect of MoDeC on epidermal HBD-2, indicating that, from among the many products of MoDeC, IL-1 was the dominant inducer of HBD-2 synthesis . In normal fresh human skin, which contains Langerhans cells and other myeloid cell types, in addition to keratinocytes, LPS also induced HBD-2 in an IL-1-dependent manner . In DNA microarray expression studies, HBD-2 was one of the most abundant mRNAs induced in epidermis by LPS-treated MoDeC, and its induction was reversed by IL-1Ra . Thus, epidermal response to LPS is potently amplified by MoDeC through IL-1-mediated signaling, leading to a selective increase in the synthesis of the antimicrobial peptide HBD-2 . This pattern of responses establishes a key role for both IL-1 and HBD-2 in the host defense reaction of the epidermis. J Biol Chem, 2003 Mar 7, 278(10), 8761 - 70 Epub 2002 Dec 20. Structure of Escherichia coli 5'-methylthioadenosine/ S-adenosylhomocysteine nucleosidase inhibitor complexes provide insight into the conformational changes required for substrate binding and catalysis; Lee JE et al.; 5'-Methylthioadenosine/S-adenosylhomocysteine (MTA/AdoHcy) nucleosidase is a key enzyme in a number of critical biological processes in many microbes . This nucleosidase catalyzes the irreversible hydrolysis of the N(9)-C(1') bond of MTA or AdoHcy to form adenine and the corresponding thioribose . The key role of the MTA/AdoHcy nucleosidase in biological methylation, polyamine biosynthesis, methionine recycling, and bacterial quorum sensing has made it an important antimicrobial drug target . The crystal structures of Escherichia coli MTA/AdoHcy nucleosidase complexed with the transition state analog, formycin A (FMA), and the nonhydrolyzable substrate analog, 5'-methylthiotubercidin (MTT) have been solved to 2.2- and 2.0-A resolution, respectively . These are the first MTA/AdoHcy nucleosidase structures to be solved in the presence of inhibitors . These structures clearly identify the residues involved in substrate binding and catalysis in the active site . Comparisons of the inhibitor complexes to the adenine-bound MTA/AdoHcy nucleosidase (Lee, J . E., Cornell, K . A., Riscoe, M . K., and Howell, P . L . (2001) Structure (Camb.) 9, 941-953) structure provide evidence for a ligand-induced conformational change in the active site and the substrate preference of the enzyme . The enzymatic mechanism has been re-examined. Planta Med, 2002 Dec, 68(12), 1082 - 7 Antimicrobial activity of the essential oil and some isolated sulfur-rich compounds from Scorodophloeus zenkeri; Kouokam JC et al.; The essential oil and several pure sulfur compounds isolated from Scorodophloeus zenkeri were tested for their antibacterial and antifungal activity using a paper disc method, the poisoned food technique, a microatmosphere method and the measurement of cellular ATP content . The essential oil completely inhibited the growth of all fungi tested including yeasts, with the exception of Aspergillus flavus, and was active against the Gram-positive bacteria studied, but not the Gram-negative organisms . 2,4,5,7-Tetrathiaoctane, 2,4,5,6,8-pentathianonane, 2,3,4,6,8-pentathianonane, 2,3,5,6,8,10-hexathiaundecane, 2,3,5-trithiahexane 5-oxide, 2,4,5,7-tetrathiaoctane 2-oxide, 2,3,5,7-tetrathiaoctane 3,3-dioxide and 2,3,5-trithiahexane 3,3-dioxide differed in their effects on the strains studied with respect to both growth and synthesis of cellular ATP . 2,3,5-Trithiahexane, 2,3,4,6-tetrathiaheptane, methyl methanethiosulfonate and bis-methyl-sulfonylmethane exhibited no antimicrobial activity. Protein Sci, 2003 Jan, 12(1), 143 - 52 Isolation and biochemical characterization of LEAP-2, a novel blood peptide expressed in the liver; Krause A et al.; The human genome contains numerous genes whose protein products are unknown in terms of structure, interaction partner, expression, and function . To unravel the function of these orphan genes, it is of particular value to isolate native forms of protein and peptide products derived from these genes . From human blood ultrafiltrate, we characterized a novel gene-encoded, cysteine-rich, and cationic peptide that we termed liver-expressed antimicrobial peptide 2 (LEAP-2) . We identified several circulating forms of LEAP-2 differing in their amino-terminal length, all containing a core structure with two disulfide bonds formed by cysteine residues in relative 1-3 and 2-4 positions . Molecular cloning of the cDNA showed that LEAP-2 is synthesized as a 77-residue precursor, which is predominantly expressed in the liver and highly conserved among mammals . This makes it a unique peptide that does not exhibit similarity with any known human peptide regarding its primary structure, disulfide motif, and expression . Analysis of the LEAP-2 gene resulted in the identification of an alternative promoter and at least four different splicing variants, with the two dominating transcripts being tissue-specifically expressed . The largest native LEAP-2 form of 40 amino acid residues is generated from the precursor at a putative cleavage site for a furin-like endoprotease . In contrast to smaller LEAP-2 variants, this peptide exhibited dose-dependent antimicrobial activity against selected microbial model organisms . LEAP-2 shares some characteristic properties with classic peptide hormones and it is expected that the isolation of this novel peptide will help to unravel its physiological role. Biol Reprod, 2003 Jan, 68(1), 95 - 104 Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans; Com E et al.; Defensins are antimicrobial peptides that play a major role in innate immunity . Using reverse transcriptase-polymerase chain reaction, immunochemistry, or both, we performed a search of all presently known defensins in rat testis, epididymis, and isolated testicular cells; in mouse testis and epididymis; and in human testis and ejaculates . In the rat, all alpha- and beta-defensins except RNP-4 were expressed within the testis, whereas alpha-defensins RNP1-2, RNP-4, and beta-defensins RBD-1 and RBD-2 were present within the epididymis . In the mouse, the cryptdin transcripts CRS1C, mBD-1, and mBD-2 were detected in the testis and epididymis, whereas mBD-3 and mBD-4 were expressed only in the epididymis, and CRS4C was absent in both organs . In the human testis, transcripts for four known defensins were expressed with the consistent exception of HBD-2 and HBD-3 . In rat interstitial tissue, resident macrophages expressed most of the defensins studied, whereas Leydig cells produced only RBD-2 . In contrast, all studied defensins except RNP-4 were present in the seminiferous tubules . Within these tubules, peritubular and Sertoli cells expressed most of the studied alpha- and beta-defensins, whereas spermatogonia displayed only alpha-defensins, but at relatively high levels . Meiotic pachytene spermatocytes expressed only beta-defensins, whereas postmeiotic spermatids and their cytoplasmic lobes displayed both types . In humans, the HBD-1 peptide was expressed mainly in the germ line from pachytene spermatocytes to late spermatids . The peptide was also present in ejaculated spermatozoa and seminal plasma, where multiple soluble forms were present . Finally, high salt concentration or dithiothreitol-sensitive cationic extracts from human seminal plasma were indeed found to display antimicrobial activity . We conclude that the male reproductive tract produces defensins that most probably assume an important, innate organ defense system against pathogens. Diagn Microbiol Infect Dis, 2002 Nov, 44(3), 259 - 63 Synergy of colistin with rifampin and trimethoprim/sulfamethoxazole on multidrug-resistant Stenotrophomonas maltophilia; Giamarellos-Bourboulis EJ et al.; Stenotrophomonas maltophilia is characterized by intrinsic resistance to a variety of antimicrobials . Therapeutic options are often limited particularly after the emergence of isolates resistant to trimethoprim/sulfamethoxazole . The application of colistin for infections caused by multidrug-resistant Gram-negative pathogens is limited due to its toxicity . In order to evaluate the activity of the interaction of colistin with rifampin or trimethoprim/sulfamethoxazole on S . maltophilia, 24 different isolates resistant to trimethoprim/sulfamethoxazole were in vitro exposed over-time to the combination of 1x and 4 x MIC of colistin with 2 microg/ml of rifampin or 2/38 microg/ml of trimethoprim/sulfamethoxazole . The applied concentrations for rifampin and trimethoprim/sulfamethoxazole reflect their mean serum levels . Synergy of colistin and rifampin was documented after the first two hours of bacterial growth for approximately 60% of isolates and it occurred with both applied concentrations of colistin . The interaction of colistin and rifampin prevented regrowth observed when single colistin was applied . Synergy of colistin and trimethoprim/sulfamethoxazole was mainly found when colistin was applied at a concentration of 4 x MIC involving 41.7% of isolates after 24 h of growth . In the presence of trimethoprim/sulfamethoxazole bacterial regrowth, observed when single colistin was applied, was prevented . It is concluded that growth of multidrug-resistant S . maltophilia is significantly inhibited by the interaction of colistin and rifampin and to a lesser extent of colistin and trimethoprim/sulfamethoxazole . These results merit further study in both the animal model and the clinical setting. Immunol Rev, 2002 Dec, 190, 137 - 45 Genomics-based approaches to gene discovery in innate immunity; Scheetz T et al.; The completion of draft sequences of the human and mouse genomes offers many opportunities for gene discovery in the field of immunology through the application of the methods of computational genomics . One arm of the innate immune system includes the antimicrobial peptides that protect multicellular organisms from a diverse spectrum of microorganisms . The beta-defensins comprise an important family of mammalian antimicrobial peptides . To better define the beta-defensin gene family, we developed an approach to search genomic databases for conserved motifs present in the beta-defensin family using HMMER, a computational search tool based on hidden Markov models (HMMs), in combination with the basic local alignment search tool . The approach was first used to identify candidate second-exon coding regions, and later applied to finding associated first exons . This strategy discovered 28 new human and 43 new mouse beta-defensin genes in five syntenic chromosomal regions . Within each syntenic cluster, the gene sequences and organization were similar, suggesting that each cluster pair arose from a common ancestor and was retained because of conserved functions . These findings demonstrate an important proof-of-principle for a genome-wide search strategy to identify genes with conserved structural motifs . Such an approach may be readily adopted to address other questions of relevance to immunology. J Appl Microbiol, 2003, 94(1), 9 - 15 Efficacy of antimicrobial filter treatments on microbial colonization of air panel filters; Verdenelli MC et al.; AIMS: To assess the activity of biostatic agents on the microbial colonization of panel filters . METHODS AND RESULTS: Microfibre glass acrylic filters, both used and unused, were examined for the presence of microorganisms . Test strains were used to verify microbial colonization of filter media . Antimicrobial agents were applied to the filter media and tested for their ability to reduce microbial colonization . The integrity of the panel filters and the antimicrobial activity trends of the filter media treated with antimicrobials were verified . A filtration efficiency test was carried out on the treated filters to evaluate filtration performance . Filters treated with antimicrobials demonstrated markedly less microbial colonization (density and varieties of species), higher filtration efficiency and delayed deterioration of the filter . CONCLUSIONS: The most important results of this study are the demonstration of preservation of the integrity of the filters and the lower release of microorganisms from treated filters . SIGNIFICANCE AND IMPACT OF THE STUDY: These results contribute to the resolution of problems concerning the microbial contamination of panel filters in the heating, ventilating and air-conditioning systems commonly used in the electronic industry, pharmaceutical industry, hospitals and other environments where the absence of contaminating particles and microorganisms is required. Mol Microbiol, 2003 Jan, 47(1), 257 - 66 Class V chitin synthase determines pathogenesis in the vascular wilt fungus Fusarium oxysporum and mediates resistance to plant defence compounds; Madrid MP et al.; Chitin, a beta-1,4-linked polysaccharide of N-acetylglucosamine, is a major structural component of fungal cell walls . Fungi have multiple classes of chitin synthases that catalyse N-acetylglucosamine polymerization . Here, we demonstrate the requirement for a class V chitin synthase during host infection by the vascular wilt pathogen Fusarium oxysporum . The chsV gene was identified in an insertional mutagenesis screen for pathogenicity mutants . ChsV has a putative myosin motor and a chitin synthase domain characteristic of class V chitin synthases . The chsV insertional mutant and a gene replacement mutant of F . oxysporum display morphological abnormalities such as hyphal swellings that are indicative of alterations in cell wall structure and can be partially restored by osmotic stabilizer . The mutants are unable to infect and colonize tomato plants or to grow invasively on tomato fruit tissue . They are also hypersensitive to plant antimicrobial defence compounds such as the tomato phytoanticipin alpha-tomatine or H2O2 . Reintroduction of a functional chsV copy into the mutant restored the growth phenotype of the wild-type strain . These data suggest that F . oxysporum requires a specific class V chitin synthase for pathogenesis, most probably to protect itself against plant defence mechanisms. Am J Gastroenterol, 2002 Dec, 97(12), 3032 - 7 Impaired host immunity contributes to Helicobacter pylori eradication failure; Borody T et al.; OBJECTIVES: Effective eradication of Helicobacter pylori (H . pylori) infection has often proved more difficult than expected . Antimicrobial resistance incompletely explains eradication failure . This study tests the hypothesis that an impaired immune response may contribute to failed eradication after standard antibiotic therapy . METHODS: Parameters of host immunity were assessed as blood T lymphocyte production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) being surrogate markers of mucosal Th1 and Th2 responses, respectively . The validity of using circulating T cell cytokines as surrogate markers of mucosal immunity was established (unstimulated lymphocyte IL-4 level correlation r2 = 0.549, p < 0.001; antigen-stimulated lymphocyte correlation r2 = 0.62, p < 0.001) . RESULTS: A total of 52 dyspeptic patients and 11 patients with previous H . pylori eradication failure were recruited into the study . There was no significant difference in secretion of IFN-gamma from peripheral blood T cells, in either unstimulated or antigen-stimulated cultures, between clinical groups . There was, however, a significant reduction in secretion of IL-4 from blood T cells in subjects failing to eradicate H . pylori compared with those who successfully eradicated the infection in both unstimulated and stimulated cultures . A significant difference in IL-4 secretion was also detected in antigen-stimulated cultures compared with that in H . pylori-positive subjects (p < 0.05) . Low levels of IL-4 secretion were detected irrespective of the number of courses of antibiotic therapy . Lower levels of IgG anti-H . pylori antibody were detected in both serum and saliva of subjects with persistent H . pylori infection after use of antibiotics compared with untreated H . pylori-positive subjects (difference not statistically significant) . CONCLUSIONS: These results support the hypothesis that impaired mucosal immunity, particularly involving the secretion of IL-4, may contribute to H . pylori eradication failure . Measurement of whole blood secretion of IL-4 may predict which patients are more likely to fail standard antibiotic therapy. Rev Med Chil, 2002 Oct, 130(10), 1165 - 9 {Verrucous endocarditis secondary to Saccharomyces cerevisiae . A case report}; Ruiz-Esquide F et al.; We report a preterm infant with 30 weeks of gestation, that received broad spectrum antimicrobials during the first days of life . At nine days of life, the infant appeared with abdominal distension and hematochezia . A systolic murmur with changing auscultatory features also appeared . An echocardiography showed an atrial vegetation . A yeast, that was identified as the emergent pathogen Saccharomyces cerevisiae appeared in two blood cultures . Treatment with amphotericin B was started, the dose was adjusted calculating the minimal inhibitory concentration of amphotericin B, and measuring plasma levels of the antimicrobial . Therefore the minimal effective dose was prescribed, avoiding its deleterious effects . After 14 days of antifungal therapy, a new echocardiography showed a reduction in the size of the atrial vegetation . At 35 days, it disappeared and amphotericin B was discontinued . On the outpatient follow up, the infant has shown a normal growth and a normal cardiac auscultation. Biopolymers, 2002, 66(4), 236 - 48 Mode of action of membrane active antimicrobial peptides; Shai Y; Water-membrane soluble protein and peptide toxins are used in the defense and offense systems of all organisms, including plants and humans . A major group includes antimicrobial peptides, which serve as a nonspecific defense system that complements the highly specific cell-mediated immune response . The increasing resistance of bacteria to conventional antibiotics stimulated the isolation and characterization of many antimicrobial peptides for potential use as new target antibiotics . The finding of thousands of antimicrobial peptides with variable lengths and sequences, all of which are active at similar concentrations, suggests a general mechanism for killing bacteria rather than a specific mechanism that requires preferred active structures . Such a mechanism is in agreement with the "carpet model" that does not require any specific structure or sequence . It seems that when there is an appropriate balance between hydrophobicity and a net positive charge the peptides are active on bacteria . However, selective activity depends also on other parameters, such as the volume of the molecule, its structure, and its oligomeric state in solution and membranes . Further, although many studies support that bacterial membrane damage is a lethal event for bacteria, other studies point to a multihit mechanism in which the peptide binds to several targets in the cytoplasmic region of the bacteria. Clin Infect Dis, 2003 Jan 1, 36(1), 40 - 5 Epub 2002 Dec 12. Broad-range bacterial polymerase chain reaction for early detection of bacterial meningitis; Saravolatz LD et al.; The diagnosis of bacterial meningitis often depends on isolation of bacteria on culture, which may take 24-48 h . DNA amplification techniques could provide rapid diagnosis, which would guide the clinician in antimicrobial therapy decisions . This study determined the clinical utility of polymerase chain reaction (PCR) for the diagnosis of meningitis with use of a broad range of bacterial primers . Seventy-four cerebrospinal fluid specimens obtained from 70 patients were subjected to PCR with use of primers derived from conserved regions of the bacterial 16S RNA gene . The test characteristics for the broad-range bacterial PCR were as follows: sensitivity, 100%; specificity, 98.2%; positive predictive value, 94.4%; and negative predictive value, 100% . Broad-range bacterial PCR may be useful for excluding the diagnosis of meningitis, and the results may influence the decision to initiate or discontinue antimicrobial therapy. J Neurovirol, 2002 Dec, 8 Suppl 2, 122 - 8 Molecular studies of cerebrospinal fluid in human immunodeficiency virus type 1-associated opportunistic central nervous system diseases--an update; Cinque P et al.; Although the incidence of opportunistic central nervous system (CNS) diseases has markedly declined in developed countries following the advent of highly active antiretroviral therapies (HAARTs), they still represent a major diagnostic and therapeutic challenge over the world . The application of nucleic acid amplification techniques to the study of cerebrospinal fluid (CSF) has contributed substantially to their diagnosis . The detection of specific microbial genomes in the CSF is now the preferred test for some CNS opportunistic diseases, such as progressive multifocal leukoencephalopathy or cytomegalovirus encephalitis . More recent developments of these techniques are the quantitative amplification techniques and postamplification studies . Quantification of nucleic acids in CSF is an important aid both at the time of diagnosis, for the interpretation of positive findings, and during patient follow-up . Postamplification analyses can provide important information with regard to clinical patient management, e.g., detection of genotypic resistance to antimicrobial drugs, and in the attempt to elucidate disease epidemiology and pathogenesis. Pathol Biol (Paris), 2002 Nov, 50(9), 547 - 51 {Determination of indicators for non-compliance with guidelines for surgical antimicrobial prophylaxis}; Thouverez M et al.; We conducted a prospective study to identify predictors of inappropriateness of surgical prophylaxis . A total of 72 surgeon-anaesthesist pairs participated in data collection . We assessed practices by addressing 5 questions: did the surgical procedure justify the use of antimicrobial prophylaxis, and was it provided? Was the correct agent used? Was the timing of prophylaxis optimal? Was the duration of prophylaxis correct? Was the dose correct? We reviewed 687 procedures, 513 (74.7%) of which were included in the analysis . The proportion of these procedures with totally compliant prescriptions was 41.7% . Of the 156 patients who received an inappropriate drug, 133 (85.3%) received a drug with a broader spectrum than that recommended . Prophylaxis lasted too long in 81 (89.0%) of the 91 patients who received prophylaxis of incorrect duration . Multivariate analysis revealed a clear association between non-compliant prophylaxis and two operation-specific factors: prosthesis implantation (with a relative risk of 2.52) and clean-contaminated operations (with a relative risk of 4.19) . More than 50% of patients received inappropriate surgical prophylaxis . Non-observance of guidelines was related to factors that did not influence the infectious potential of the flora. J Control Release, 2003 Jan 9, 86(1), 101 - 13 Liquid formulation of a novel non-fluorinated topical quinolone, T-3912, utilizing the synergic solubilizing effect of the combined use of magnesium ions and hydroxypropyl-beta-cyclodextrin; Yamakawa T et al.; T3912 is a non-fluorinated topical quinolone antimicrobial agent currently under development . Its pK(a1) and pK(a2) values were determined as 5.6 and 7.5, respectively, and its intrinsic solubility at pH 7 was found to be approximately 2 microg/ml . This study evaluates the combined use of Mg(2+) ions, hydroxpyropyl-beta-cyclodextrin (HPbetaCD) and polyvinylpyrrolidone (PVP) in order to obtain a stable aqueous liquid formulation of T-3912 . The use of Mg(2+) ions alone resulted in the improved solubility of T-3912 at physiological pH, however, it became unstable during storage . HPbetaCD increased T-3912 solubility with relatively high apparent association constant (K(1:1)=9.6 x 10(3) M(-1)) that was determined by a phase-solubility method at pH 7.5 . Moreover, a binary system of Mg(2+) and HPbetaCD exerted a synergetic effect, such that the solubility of T-3912 increased a remarkable 500-fold . Furthermore, the addition of PVP prevented precipitation during storage, and as a result, the liquid formulation of T-3912 (1000 microg/ml) showed good stability under various conditions, i.e., in a refrigerator at 25 degrees C/60% RH and at 40 degrees C/75% RH for 6 months . The effect of light exposure of 1200000 lux.h was also tested . This combined system of Mg(2+) ions, HPbetaCD and PVP has potential as a liquid formulation of T-3912 for topical application, especially for opthalmic use. Fitoterapia, 2002 Dec, 73(7-8), 744 - 8 Antimicrobial activity of Michelia champaca; Khan MR et al.; The methanol extracts of leaves, seeds, stem and root barks, stem and root heart-woods of Michelia champaca and the obtained fractions (petrol, dichloromethane, ethyl acetate, butanol) exhibited a broad spectrum of antibacterial activity . Fractionation drastically enhanced the level of activity particularly in all fractions of the stem bark and dichloromethane fraction of the root bark . Some fractions of the leaves, stem and root barks demonstrated antifungal activity against some of the tested moulds . Liriodenine was the active constituent of the root bark, with a broader and, in some cases, better level of activity as compared to the standard . Fitoterapia, 2002 Dec, 73(7-8), 741 - 3 Antimicrobial activity of Calophyllum soulattri; Khan MR et al.; The methanol extracts of leaves, root and stem barks of Calophyllum soulattri were partitioned with petrol, dichloromethane, ethyl acetate . The extracts demonstrated a range of antibacterial activity, improved on fractionation . None were found to be active against the moulds . Fitoterapia, 2002 Dec, 73(7-8), 737 - 40 Antimicrobial activity of Terminalia complanata and Flacourtia zippelii; Khan MR et al.; A broad spectrum of antibacterial activity was exhibited by the methanol extracts of leaves, root and stem barks of Terminalia complanata and Flacourtia zippelii and their subsequent fractions (petrol, dichloromethane, ethyl acetate) . Fractionation enhanced the activity particularly in the ethyl acetate fractions of the stem and root barks of T . complanata . No activity was observed against the moulds . Fitoterapia, 2002 Dec, 73(7-8), 713 - 5 Antimicrobial activity of Psidium guajava L; Abdelrahim SI et al.; Psidium guajava aqueous bark and methanolic extracts were found to possess anti-bacterial activity . Fitoterapia, 2002 Dec, 73(7-8), 698 - 700 Antimicrobial activity of Pithecolobium avaremotemo bark; de Araujo CW et al.; The Pithecolobium avaremotemo bark methanolic extract exhibited a broad spectrum and high levels of antimicrobial activity . Fitoterapia, 2002 Dec, 73(7-8), 695 - 7 Antimicrobial activity of the macrofungus Lepista nuda; Dulger B et al.; The 60% methanolic extract of Lepista nuda exhibited antimicrobial activity . Hum Gene Ther, 2002 Nov 20, 13(17), 2017 - 25 A model for antimicrobial gene therapy: demonstration of human beta-defensin 2 antimicrobial activities in vivo; Huang GT et al.; We transfected host cells with an antimicrobial peptide/protein-encoding gene as a way to enhance host defense mechanisms against infection . The human beta-defensin 2 (HBD-2) gene was chosen as a model because its protein does not require cell type-specific processing . Using a retroviral vector carrying HBD-2 cDNA, we treated several mouse or human cell lines and primary cell cultures including fibroblasts, salivary gland cells, endothelial cells, and T cells . All transduced cells produced detectable HBD-2 . In Escherichia coli gel overlay experiments, secreted HBD-2 from selected cell lines showed potent antimicrobial activity electrophoretically identical to that of purified HBD-2 . We then used a mouse model (nonobese diabetic/severely compromised immunodeficient {NOD/SCID}) to test HBD-2 antimicrobial activities in vivo . HT-1080 cells carrying HBD-2 or control vector were implanted subcutaneously into NOD/SCID mice to allow tumor formation . Escherichia coli was then injected into each tumor mass . Tumors were resected after 16 hr and homogenized for bacterial colony-forming unit analysis . Compared with control tumors, HBD-2-bearing tumors contained only 7.8 +/- 3.3% viable bacteria . On the basis of this demonstration of HBD-2 in vivo antimicrobial activity, enhancement of antibacterial host defense by HBD-2 gene therapy may be feasible. Pediatr Infect Dis J, 2002 Dec, 21(12), 1161 - 4 Ecthyma gangrenosum: considerations in a previously healthy child; Zomorrodi A et al.; Ecthymagangrenosum is a skin lesion that is most commonly caused by . Although ecthyma gangrenosum usually develops in patients with underlying immunodeficiencies or chronic diseases, there have been reports of its appearance in previously healthy children . A review of such patients in the English literature showed that most of them had either previously undetected immunodeficiencies or transient risk factors that predisposed them to the development of ecthyma gangrenosum . We report a patient without apparent antecedent predisposing risk factors for ecthyma gangrenosum who developed chronic neutropenia 1 week after presentation . It is important for the primary care provider to recognize ecthyma gangrenosum, treat it with appropriate antimicrobial agents and investigate the patient for occult immunodeficiencies. Pediatr Infect Dis J, 2002 Dec, 21(12), 1110 - 5 Tympanostomy tube placements, sociodemographic factors and parental expectations for management of acute otitis media in Iceland; Arason VA et al.; BACKGROUND: Widespread antimicrobial use is a risk factor for development of antimicrobial resistance . Antimicrobial treatment of acute otitis media (AOM) may not always be necessary . Little is known about the influence of parental expectations on physicians' decision-making in relation to treatment of AOM . Evidence is insufficient as to whether tympanostomy tube placement reduces antibiotic consumption . METHODS: We randomly selected 1,030 children 1 to 6 years old living in 4 geographic areas in Iceland to be invited to participate in the study . Information about sociodemographic factors, antimicrobial prescriptions and their indications during the preceding 12 months, tympanostomy tube placements and parental views on antimicrobial use and bacterial resistance were obtained from a questionnaire completed by the parents and medical records . RESULTS: The incidence of AOM episodes resulting in antimicrobial prescription for 804 children recruited into the study was 0.7 (95% confidence interval, 0.6 to 0.8) per child per year, highest among children age 1 year, i.e . 1.8 prescriptions (95% confidence interval, 1.4 to 2.2) . The cumulative incidence of tympanostomy tube placements was approximately 30% . Antimicrobial use during the preceding 8 weeks for children with and without tubes did not differ (P = 0.36) . Fifteen percent of children with tubes had received antimicrobials during the preceding 8 weeks at last once for AOM compared with 14% of those without tubes (P = 0.97) . Parents in the area where antimicrobial consumption was lowest were less likely to accept antimicrobial treatment than parents in the other areas (P = 0.005) . Parents of children who had previously received antimicrobials for AOM were more likely to accept antimicrobials (P = 0.04) . CONCLUSIONS: Parental expectations to antimicrobial treatment and awareness about resistance development appear to influence treatment strategies for AOM . The high rate of tympanostomy tube placement in preschool children does not result in reduced antimicrobial consumption. J Med Microbiol, 2003 Jan, 52(Pt 1), 41 - 5 Human beta-defensin-2 induction in Helicobacter pylori-infected gastric mucosal tissues: antimicrobial effect of overexpression; Uehara N et al.; The objective of this study was to understand more of the innate immune response to Helicobacter pylori by determining the expression of human beta-defensin-2 (hBD-2) in various gastric mucosal tissues and MKN45 gastric cancer cells with or without H . pylori . Semi-quantitative TaqMan RT-PCR and immunohistochemistry were carried out . The antimicrobial effects of a transfected hBD-2 gene against H . pylori were also evaluated . The results showed that hBD-2 was expressed in inflamed gastric mucosal tissues with H . pylori infection, but not in the absence of H . pylori infection . Expression was also detected in gastric cancers in patients with H . pylori infection . Expression was induced in the MKN45 gastric cancer cell line by H . pylori in a manner dependent on the abundance of bacteria . hBD-2-transfected 3T3J2-1 cells secreted hBD-2 protein into the culture medium and this protein inhibited growth of H . pylori completely . The results suggest that hBD-2 may be involved in the pathophysiology of H . pylori-induced gastritis. Sci STKE . 2002 Dec 17;2002(163):PE53. Mono-ADP-ribosylation: a tool for modulating immune response and cell signaling; Corda D et al.; Mono-ADP-ribosylation is a posttranslational modification of cellular proteins that has the potential to regulate various cell functions . This reaction consists of the enzymatic transfer of ADP-ribose to specific acceptor amino acid residues (predominantly arginine and cysteine) . The best-known cellular ADP-ribosyltransferases (the enzymes that catalyze this reaction) are the seven ectoenzymes, members of the ART family . Recently, ADP-ribosylated human neutrophil-derived peptide (HNP-1, an antimicrobial peptide secreted by immune cells) has been identified in the bronchoalveolar lavage fluid from individuals who smoke cigarettes . This demonstrates that ADP-ribosylation of HNP-1 occurs in vivo . In vitro experiments have indicated that ART-1, an enzyme also present in the airway epithelium, specifically modifies Arg(14) of the HNP-1, causing the loss of the peptide's antimicrobial and cytotoxic activity, while preserving its chemotactic activity . From a functional point of view, these data support a role of ADP-ribosylation in the innate immune response . Additional functions proposed for the ADP-ribosylation reaction involve the intracellular ADP-ribosyltransferases, which are molecularly unrelated to the ARTs and intervene in cell signaling and metabolism cascades . The growing understanding of the biological roles of protein and peptide ADP-ribosylation represents a powerful tool for novel pharmacological interventions. Biophys Chem, 2002 Dec 10, 101-102, 239 - 47 Binding affinities and geometries of various metal ligands in peptide deformylase inhibitors; Madison V et al.; Removal of the N-terminal formyl group from newly synthesized proteins by the enzyme peptide deformylase (PDF) is essential for normal growth of bacteria but not higher organisms . Recently, PDF has been explored as a target for novel antibiotics . Screening a collection of natural products for antimicrobial activity identified actinonin and two matlystatin analogs as potent PDF inhibitors . A number of synthetic analogs of these natural products were prepared and their inhibitory potency determined . Previous work has shown that PDF is an iron metalloproteinase also containing a catalytic glutamic acid residue . Ligation of the ferrous cation is an essential feature of potent inhibitors . The structures of actinonin, a matlystatin analog and a synthetic inhibitor complexed with PDF were determined by crystallography . A quantum mechanics/molecular mechanics (QM/MM) method was used to reproduce the geometry of known complexes, to predict the protonation state in the active site and to predict the geometry of additional complexes . The requirement for protonation of the active site glutamate anion is an important factor in understanding the potency of inhibitors with acidic iron-ligating groups such as hydroxamate and carboxylate . Even though potent inhibitors of PDF have been discovered, their bacteriostatic mechanism of action and the rapid development of resistance in vitro may limit their potential as antibacterial drugs . Drugs, 2003, 63(1), 101 - 33 Pantoprazole: an update of its pharmacological properties and therapeutic use in the management of acid-related disorders; Cheer SM et al.; Pantoprazole (Protonix) is an irreversible proton pump inhibitor (PPI) that reduces gastric acid secretion . In combination with two antimicrobial agents (most commonly metronidazole, clarithromycin or amoxicillin) for 6-14 days, pantoprazole 40 mg twice daily produced Helicobacter pylori eradication rates of 71-93.8% (intent-to-treat {ITT} or modified ITT analysis) in patients without known antibacterial resistance . Pantoprazole-containing triple therapy was at least as effective as omeprazole- and similar in efficacy to lansoprazole-containing triple therapy in large trials . In the treatment of moderate to severe gastro-oesophageal reflux disease (GORD), oral pantoprazole 40 mg/day was as effective as other PPIs (omeprazole, omeprazole multiple unit pellet system, lansoprazole and esomeprazole) and significantly more effective than histamine H(2)-antagonists . Pantoprazole 20 mg/day provided effective mucosal healing in patients with GORD and mild oesophagitis . Intravenous pantoprazole 40 mg/day can be used in patients who are unable to take oral medication . Oral pantoprazole 20-40 mg/day for up to 24 months prevented relapse in most patients with healed GORD . According to preliminary data, oral pantoprazole 20 or 40 mg/day was effective at healing and preventing non-steroidal anti-inflammatory drug (NSAID)-related ulcers, and intravenous pantoprazole was at least as effective as intravenous ranitidine in preventing ulcer rebleeding after endoscopic haemostasis . Oral or intravenous pantoprazole up to 240 mg/day maintained target acid output levels in most patients with hypersecretory conditions, including Zollinger-Ellison syndrome . Oral and intravenous pantoprazole appear to be well tolerated in patients with acid-related disorders in short- and long-term trials . Tolerability with oral pantoprazole was similar to that with other PPIs or histamine H(2)-antagonists in short-term trials . Formal drug interaction studies have not revealed any clinically significant interactions between pantoprazole and other agents . In conclusion, pantoprazole is an effective agent in the management of acid-related disorders . As a component of triple therapy for H . pylori eradication and as monotherapy for the healing of oesophagitis and maintenance of GORD, pantoprazole has shown similar efficacy to other PPIs and greater efficacy than histamine H(2)-antagonists . Limited data suggest that it is also effective in Zollinger-Ellison syndrome and in preventing ulcer rebleeding . Pantoprazole is well tolerated with minimal potential for drug interactions . The availability of pantoprazole as both oral and intravenous formulations provides flexibility when the oral route of administration is not appropriate . Thus, pantoprazole is a valuable alternative to other PPIs in the treatment of acid-related disorders. Transpl Infect Dis, 2002, 4 Suppl 3, 67 - 8 Summary: future directions in antifungal therapy; Fishman JA; The development of strategies for the prevention and treatment of invasive fungal infection is reviewed . The optimal deployment of antifungal agents is impeded by delays in diagnosis, which reflect the need for tissue samples for histopathology and/or the slow growth of organisms in culture for identification . Further, the lack of rapid and standardized methods for antimicrobial susceptibility testing has been identified as a major hurdle to optimal management . It is likely that combinations of antifungal agents will be needed to accelerate the clinical response to therapy (i.e., killing of fungus in tissues more rapidly) . Such combinations may have the capacity to reduce toxicity while providing either true additive or synergistic activities or improved pharmacokinetics to "target" infection in multiple sites . Preclinical studies and clinical trials will begin to identify candidate therapies for invasive fungal infections in transplantation. J Vet Pharmacol Ther, 2002 Dec, 25(6), 455 - 9 Pharmaco-epidemiology and -economics should be developed more extensively in veterinary medicine; Chauvin C et al.; Pharmaco-epidemiology, which has emerged within the last 20 years as a new discipline in human medicine, deals with the quantities of drugs consumed and their effects on populations in terms of epidemiological concepts and tools . To a lesser extent, it is also practised in veterinary medicine . The applications presented in this review are illustrative of pharmaco-epidemiological and -economical concepts . Assessment of drug consumption, the study of adverse drug effects, and the economic implications of drug use are the three main fields considered . Developments can be expected in veterinary medicine within the next few years relative to novel areas of interest such as antimicrobial resistance and new therapeutic class uses . These applications will require methodological progress and the elimination of current gaps . Pharmaco-epidemiological methods need to be developed, which implies close co-operation between statisticians, pharmacologists, veterinary practitioners and epidemiologists . A greater use of the term 'pharmaco-epidemiology' as a keyword in literature would facilitate recognition of this domain which associates closely epidemiology and pharmacology. Helicobacter, 2002 Dec, 7(6), 364 - 6 No association between Helicobacter pylori genotypes and antibiotic resistance phenotypes within families; Zschausch HC et al.; BACKGROUND: Triple therapy combining a proton pump inhibitor with two antibiotics, e.g . clarythromycin (CLR), metronidazole (MTZ) or amoxicillin (AMX), represents the standard in Helicobacter pylori eradication regimens . Resistance to antimicrobial agents, particularly MTZ (up to 56% in Western countries) and CLR (up to 15% in southern Europe), is frequently observed and may be associated with treatment failure {1} . Recently, several studies indicated that individual H . pylori colonies from a single anatomic site may not always yield identical genotypes, or the identical patterns of susceptibility to antibiotics {2-5} . Representative for every single patient we analyzed 27 H . pylori antrum isolates for susceptibility to antimicrobial agents in order to test whether identical H . pylori genotypes exhibit a similar pattern of susceptibility to antibiotics . METHODS: PCR, RELP, PFGE, antibiotic susceptibility testing . RESULTS: H . pylori genotype and antibiotic susceptibility pattern in families do not segregrate . CONCLUSION: Molecular typing of H . pylori from family members does not predict antibiotic susceptibility pattern. Phytochemistry, 2003 Jan, 62(2), 203 - 7 Antimicrobial constituents from the rhizomes of Rheum emodi; Babu KS et al.; The bioassay-guided chemical examination of the rhizomes of R . emodi resulted in the isolation of two new oxanthrone esters, revandchinone-1, revandchinone-2, a new anthraquinone ether revandchinone-3 and a new oxanthrone ether, revandchinone-4 . Their structures were established based on spectroscopic and degradative evidence . Occurrence of oxanthrone ether is reported for the first time . The anti bacterial and anti fungal activity of the isolates is studied. Symp Ser Soc Appl Microbiol, 2002, (31), 144S - 157S Significance of biocide usage and antimicrobial resistance in domiciliary environments; Bloomfield SF; Recent events have raised awareness of the need for effective hygiene in the home . Not least is the requirement to reduce antibiotic resistance by reducing the need for antibiotic prescribing . Current evidence suggests that improved hygiene in the domestic setting could have a significant impact . Recently, it has been suggested that widespread biocide usage, particularly in consumer products, may be a contributory factor in antibiotic resistance . In developing home hygiene policies, however, it is important that biocide use as an integral part of good hygiene practice is not discouraged in situations where there is real benefit . Although laboratory data indicate possible links, it is necessary to assess whether and to what extent biocide exposure could contribute to antibiotic resistance in clinical practice . The extent to which reduced susceptibility to biocides resulting from biocide exposure could compromise their 'in-use' effectiveness must also be considered . Equally, it is important that changes in susceptibility induced by biocide exposure are assessed relative to those induced by antibiotic exposure or the phenotypic changes induced by 'normal' environmental 'stresses' . It is proposed that to be effective, home hygiene policy should be based on the concept of risk assessment and risk prevention . Using this approach, critical risk situations are identified and appropriate hygiene procedures applied to reduce risks . This may involve either soap and water cleaning, or cleaning combined with a disinfection process . A 'targeted' hygiene approach not only provides the most effective means of preventing infectious disease, it also offers a means of addressing concerns about 'too much hygiene' and 'too many antibacterials' amongst a public who have lost confidence regarding appropriate hygiene for their home environment. Symp Ser Soc Appl Microbiol, 2002, (31), 16S - 27S Bacterial target sites for biocide action; Maillard JY; Although biocides have been used for a century, the number of products containing biocides has recently increased dramatically with public awareness of hygiene issues . The antimicrobial efficacy of biocides is now well documented; however, there is still a lack of understanding of their antimicrobial mechanisms of action . There is a wide range of biocides showing different levels of antimicrobial activity . It is generally accepted that, in contrast to chemotherapeutic agents, biocides have multiple target sites within the microbial cell and the overall damage to these target sites results in the bactericidal effect . Information about the antimicrobial efficacy of a biocide (i.e . the eta-value) might give some useful indications about the overall mode of action of a biocide . Bacteriostatic effects, usually achieved by a lower concentration of a biocide, might correspond to a reversible activity on the cytoplasmic membrane and/or the impairment of enzymatic activity . The bacteriostatic mechanism(s) of action of a biocide is less documented and a primary (unique?) target site within the cell might be involved . Understanding the mechanism(s) of action of a biocide has become an important issue with the emergence of bacterial resistance to biocides and the suggestion that biocide and antibiotic resistance in bacteria might be linked . There is still a lack of understanding of the mode of action of biocides, especially when used at low concentrations (i.e . minimal inhibitory concentration (MIC) or sublethal) . Although this information might not be required for highly reactive biocides (e.g . alkylating and oxidizing agents) and biocides used at high concentrations, the use of biocides as preservatives or in products at sublethal concentrations, in which a bacteriostatic rather than a bactericidal activity is achieved, is driving the need to better understand microbial target sites . Understanding the mechanisms of action of biocides serves several purposes: (i) it will help to design antimicrobial formulations with an improved antimicrobial efficacy and (ii) it will ensure the prevention of the emergence of microbial resistance. J Pak Med Assoc, 2002 Jun, 52(6), 233 - 9 Role of dexamethasone in acute bacterial meningitis in adults; Ahsan T et al.; OBJECTIVE: To evaluate the role of dexamethasone as adjunctive therapy in adult acute bacterial meningitis (ABM) in two groups of patients treated with antibiotics alone or a combination of antibiotics and dexamethasone . DESIGN: Systematic sampling interventional open cohort study . SETTING: Department of Medicine (Medical Unit II), Jinnah Postgraduate Medical Centre, Karachi . PATIENTS: Sixty eight patients aged 12-85 years admitted in Medical Unit II and diagnosed to have ABM . Patients were divided into two groups . Group A received anti-microbial therapy for 14 days (a combination of benzyl penicillin 6 million units I/V 6 hourly and chloramphenicol 1 gm I/V 6 hourly) and group B received the same antimicrobial therapy with dexamethasone 0.6 mg/kg/day in 3 divided doses for 4 days . MAIN OUTCOME MEASURES: Differences in mortality and morbidity in the two groups and differences in the CSF inflammatory parameters between the two groups of patients . RESULTS: There was early resolution of fever, headache and altered consciousness in group B as compared to group A . Cranial nerves involvement was lower in group B . There was no difference in the occurrence of other focal neurological deficits between the two groups . CSF inflammatory parameters (glucose, protein and WBC count) were significantly better in group B by day 5 . No complications attributable to dexamethasone were seen in group B . CONCLUSION: There was early resolution of symptoms and CSF inflammatory parameters in the group that received dexamethasone as adjuvant therapy . Mortality was lower in the group treated with dexamethasone but the difference was not statistically significant . Dexamethasone should be administered to all adults patients with ABM. Boll Chim Farm, 2002 Sep-Oct, 141(5), 385 - 8 In vitro antimicrobial interactions of arthemeter with some 4-quinolones; Esimone CO et al.; Bacterial infections often co-exist with acute malarial attacks . The effect of combining arthemeter (a new antimalarial) with some commonly used 4-quinolones (ciprofloxacin, pefloxacin, norfloxacin and nalidixic acid) was investigated in-vitro with a view to providing data for the design of drug regimens for the treatment of such infections . While arthemeter demonstrated no antibacterial activity whatsoever against any of the test microorganisms (E . coli and Staph . aereus), the 4-quinolones shared marked activity . Comparative analyses of the activity of each quinolone alone and in combination with arthemeter showed 0% 43.8%, 44.9% and -12.2% change in the minimum inhibitory concentration (MIC) of nalidixic acid pefloxacin, ciprofloxacin and norfloxacin respectively against E . coli and -17.5%, 22.3% 35.8% and 50.9% change in the MICs of the same respective drugs against Staph . aureus . These changes in MIC were statistically significant (Pf0.05) . With respect to infections caused by E . coli and E . coli, the combination of artemether with ciprofloxacin or pefloxacin proves to be a rational chemotherapeutic regimen when such infection co-exist with malaria. Boll Chim Farm, 2002 Sep-Oct, 141(5), 372 - 8 Thioglycolic acid and pyrazole derivatives of 4(3H)-quinazolinone: synthesis and antimicrobial evaluation; Farghaly AM et al.; New derivatives of 4(3H)-quinazolinone were synthesized and evaluated for their antibacterial and antifungal activity . The derivatives are: 3-Aryl-2-{3-aryl-1-(carboxymethylthio)-3-oxopropyl)}-4(3H)-quinazolinones 2a-f; 3-Aryl-2-(3-aryl-1H-pyrazol-5-yl)-4(3H)-quinazolinones 3a-f; 3-Aryl-2-(1,3-diaryl-1H-pyrazol-5-yl)-4(3H)-quinazolinones 4a-f; 3-Aryl-2-(3-aryl-1-thiocarbamoyl-1H-pyrazol-5-yl)-4(3H)-quinazolinones 5a-f; 3-Aryl-2-{3-aryl-1-(carboxymethylthio)-3-hydroxyiminopropyl)}-4(3H)- quinazolinones 6a-f; and 3-Aryl-2-{3-aryl-1-(carboxymethy- lthio)-3-thiocarbamoyliminopropyl)}-4(3H)-quinazolinones 7a-f . Some of the tested compounds showed activity comparable to that of the standard references used. J Periodontol, 2002 Nov, 73(11), 1285 - 91 Pharmacokinetic profile of a locally administered doxycycline gel in crevicular fluid, blood, and saliva; Kim TS et al.; BACKGROUND: With the help of so-called controlled release delivery systems, the half-life period of locally administered antibiotics in gingival crevicular fluid (GCF) can be extended significantly . The aim of this study was to characterize the delivery profile of a new one-component 14% doxycycline free amine gel for local application . Pharmacokinetics of doxycycline (DOXY) were analyzed in GCF, saliva, and serum . METHODS: Twenty patients with persisting or recurring pockets (probing depths > or = 5 mm and bleeding on probing) after mechanical treatment (surgical or non-surgical) took part in the study . In each patient 1 periodontal defect was treated with DOXY gel . Samples of GCF, saliva, and serum were obtained before application of DOXY gel; 15 minutes after application; at 2 and 5 hours; and at 1, 2, 3, 4, 7, 9, and 11 days after application . Separation and quantitative measurement of DOXY was performed with high performance liquid chromatography and UV detection at lambda = 260 nm . RESULTS: Coefficients of variation were lower than 2% (intraassay) and 4% (interassay), respectively . For concentrations between 50 to 1000 microg/ml, we found a linear relationship between expected and measured DOXY values (linear coefficient of correlation: r = 0.998) . Within the first 5 hours after application, concentration of DOXY in GCF (maximum after 15 minutes 19.97 +/- 5.85 mg/ml) and saliva (maximum after 15 minutes 17.83 +/- 2.84 mg/ml) was similar . Then concentration fell to a lower level (28.90 +/- 19.44 microg/ml) compared to GCF (577.41 +/- 127.34 microg/ml) after 3 days . Up to 10 days after application, the concentration of DOXY in GCF was 34.24 microg/ml . With the exception of 1 patient, all serum samples were DOXY-negative . CONCLUSIONS: 1) After subgingival application of biodegradable 14% doxycycline gel, mean doxycycline levels in GCF that exceeded 16 microg/ml could be maintained for at least 12 days . Thus, the antimicrobial agent may be classified as a controlled release device . 2) The antibiotic effect was limited mainly to the subgingival sites of application of the doxycycline gel . 3) The doxycycline gel possesses the pharmacokinetic and clinical properties to deliver efficacious levels of antibiotics to the periodontal pocket and to maintain these levels for at least 1 week without the need of further drug retention by a periodontal dressing. Ophthalmologe, 2002 Dec, 99(12), 949 - 59 {Autologous serum-eye-drops for ocular surface disorders . A literature review and recommendations for their application}; Geerling G et al.; The natural tear film has mechanical, optical, antimicrobial and nutritional properties . Tear film components, such as EGF, fibronectin and vitamin A, play a vital role in the proliferation, migration and differentiation of the corneal and conjunctival epithelium . In ocular surface disease, such as severe dry eye, the epithelia may be depleted of these nutritional factors . Replacing the aqueous component of tears alone,by using pharmaceutical tear substitutes,often has little effect on the ocular surface.Eye-drops prepared from autologous serum are a new treatment option for severe ocular surface disease.They can be produced according to the regulations on drug use as an unpreserved blood preparation.Autologous serum eye-drops are non-allergenic and their biomechanical and biochemical properties are similar to normal tears . In cell culture experiments, serum was found to be superior to preserved or unpreserved pharmaceutical products in the maintenance of human keratinocyte morphology and function . It supports the migration of corneal epithelial cells and the differentiation of conjunctival epithelial cells.The first clinical cohort studies report its successful use for severe dry eyes and persistent epithelial defects . In these studies, however, varying methods for the preparation and different concentrations of autologous serum eye-drops were used.These methodological variations determine the biochemical properties and thus the epitheliotrophic effect of serum eye-drops . In this review we summarise the currently available clinical evidence, discuss relevant legislatory restrictions and describe a standard operating protocol for the use of serum eye drops . This has to be evaluated and optimised in more detail before any meaningful, randomised, controlled trial can attempt to establish the role of serum eye-drops in the management of severe ocular surface disease. J AOAC Int, 2002 Nov-Dec, 85(6), 1415 - 9 Stability of sulfonamides, nitrofurans, and chloramphenicol residues in preserved raw milk samples measured by liquid chromatography; Noa M et al.; A stability study was made of 10 antimicrobials: 6 sulfonamides, 3 nitrofurans, and chloramphenicol residues in raw milk samples preserved with 0.1 % potassium dichromate (K2Cr2O7) and 0.05% mercuric bichloride (HgCl2) during cold storage for 7 days . Preserved milk samples fortified with 50 ppb of each antimicrobial were analyzed by liquid chromatography (modified AOAC Method 993.32) . Drugs were extracted with chloroform-acetone after solvent evaporation residues were dissolved with aqueous sodium acetate buffer solution (0.02M, pH 4.8), and fat was removed with hexane . Sulfonamides and chloramphenicol were detected at 275 nm (UV) by using a gradient system of sodium acetate buffer solution-acetonitrile starting at 95 + 5 (v/v) and finishing at 80 + 20 (v/v) . Nitrofurans were detected at 375 nm (UV) isocratically with sodium acetate buffer solution-acetonitrile (80 + 20, v/v) . Residues stability was measured through recovery data . Sulfamethoxazole, sulfachloropyridazine, nitrofurazone, furazolidone, and furaltadone residues remained stable in the presence of either preservative for 7 days . Sulfamethazine and chloramphenicol were not affected by K2Cr2O7, but had significant losses (p <0.05) when HgCl2 was used: 26.2 and 13.4%, respectively . Average recoveries of sulfamonomethoxine, sulfamerazine, and sulfathiazole significantly decreased by Day 7, with losses of 17.1, 17.2, and 23.2% for K2Cr2O7, and 23.3, 20.7, and 48.0% for HgCl2, respectively . During 5 days of cold storage all antimicrobials tested, except sulfathiazole, remained stable in milk samples preserved with 0.1 % K2Cr2O7 or 0.05% HgCl2. Curr Drug Targets Immune Endocr Metabol Disord, 2001 May, 1(1), 13 - 30 Pathogenetic aspects of sepsis and possible targets for adjunctive therapy; Rigato O et al.; The outcome of patients with sepsis arises from multiple factors affecting both the host and the invading microorganisms . Age, presence of underlying disease, source of infection and some specific etiological agents have been related to prognosis . Appropriateness of antimicrobial therapy, considering the in vitro susceptibility tests for the infecting bacteria, has been strongly associated with the outcome . Therefore even after the cascade of sepsis has been triggered, the control of bacteria growth is still fundamental for the outcome of the infection . This is a major distinction point from experimental studies in which whole killed bacteria and their products are used as model of sepsis . However, even within the setting of adequate antimicrobial use, patients still die of sepsis . Thus, strategies focusing on further therapy targets are an important area of interest for basic and clinical research . Although such adjunctive sepsis therapy has failed to achieve consistent better survival rates so far, nevertheless, it improved our understanding of the pathophysiological events seen in sepsis that the possibility that a new and effective treatment may arise has been warmly considered . In this paper we aim to review some aspects of the pathogenesis of sepsis, focusing on recent advances and on possible targets for adjunctive therapy . Published clinical trials and experimental data supporting such trials are commented on. Chemotherapy, 2002 Dec, 48(5), 259 - 66 Esberitox N as supportive therapy when providing standard antibiotic treatment in subjects with a severe bacterial infection (acute exacerbation of chronic bronchitis) . A multicentric, prospective, double-blind, placebo-controlled study; Hauke W et al.; 53 patients with planned antibiotic therapy for the treatment of acute exacerbation of chronic bronchitis as an example of a severe bacterial infection requiring antibiotics were included in a prospective, multicentre, double-blind, placebo-controlled study . The chronic bronchitis was staged by forced expiratory volume of the 1st second (FEV(1)) measured in the infection-free interval prior to the current episode and had to be between 35 and 75% for the predicted value . Patients were randomly assigned to receive newer macrolide antibiotics plus either Esberitox N or placebo . Antibiotic therapy was administered according to generally accepted guidelines and Esberitox N or placebo was given for 28 days . The baseline-adjusted means for FEV(1) (%) on day 10 were 68.7 points for the Esberitox N group and 59.2 points for the placebo group (p = 0.0303) . For FEV(1) the difference between the two treatment groups was 267 ml (p = 0.0499) . The time to half maximal improvement was 5.7 days in the Esberitox N group compared to 12.8 days in the placebo group . The treatment was well tolerated; no serious adverse events were documented . In conclusion, comedication of antibiotics with Esberitox N in subjects with acute exacerbation of chronic bronchitis seems to be of benefit for the patient . Apparently, therapy with Esberitox N leads to a faster recovery from this severe bacterial infection, possibly via preventing an impairment of the host's immune system which might otherwise occur as a consequence of aggressive antimicrobial therapeutics . J Chem Ecol, 2002 Oct, 28(10), 1971 - 85 Chemical ecology of marine microbial defense; Engel S et al.; Because marine animals and plants are continuously exposed to a large diversity of potentially harmful microorganisms, it seems reasonable to hypothesize that potential hosts might produce bioactive compounds to deter microbial attack . However, little is known about how host metabolites may defend against harmful microbes or facilitate the growth or colonization of helpful symbionts . While there is a large body of literature describing the antimicrobial activities of marine secondary metabolites, we are only now beginning to understand how these compounds function in an ecological context . For example, there is mounting evidence that nontoxic concentrations of secondary metabolites can have significant effects on microbial behavior, suggesting that certain host-microbe interactions are chemically mediated . Herein, we discuss the importance of employing ecologically relevant assays to elucidate microbiological effects and the need to develop a better understanding of host-microbe associations within an ecologically realistic context . Continued research in this field along with improved techniques will certainly provide further insight into how microbes have influenced the evolution of secondary metabolite production in marine organisms. Trends Parasitol, 2002 Nov, 18(11), 475 - 6 Antimicrobial peptides versus parasitic infections? Vizioli J, Salzet M. Reports of antimicrobial peptides generally have evaluations of their antibacterial and antifungal activities . By contrast, little is known of their activities against protozoan and metazoan parasites . In vitro antiparasitic assays suggest that antimicrobial peptides could represent a powerful tool for the development of novel drugs to fight the parasite in the vertebrate host, or to complement current therapeutic strategies. J Periodontal Res, 2002 Dec, 37(6), 416 - 24 Interaction of human salivary mucin MG2, its recombinant N-terminal region and a synthetic peptide with Actinobacillus actinomycetemcomitans; Liu B et al.; The antimicrobial properties of human salivary mucin MG2 against the periodontal pathogen, Actinobacillus actinomycetemcomitans (A . actinomycetemcomitans), were investigated using purified MG2, rNMUC7 (a recombinant polypeptide containing residue 1-144 of MG2) and synthetic peptides PEP1 (residue 1-17) and PEP2 (residue 47-63) . MG2 and rNMUC7 bound to A . actinomycetemcomitans strains SUNY75, SUNY465, SUNY523, 652 and JP2 in a liquid phase binding assay . The bactericidal activities of rNMUC7, PEP1 and PEP2 against A . actinomycetemcomitans SUNY523 were examined in a colony forming unit killing assay . The LD50 for rNMUC7 was 9 microM, for PEP2 was 20 microM and PEP1 did not exhibit bactericidal activity . The primary structure of these polypeptides was analyzed and a direct relationship between net positive charge and bactericidal activity was found . Screening of saliva samples from 60 individuals on Western blots probed with an anti-MG2 antibody against PEP2 revealed that a 20 kDa MG2 fragment was present in 66% of subjects and that this fragment was not present in glandular secretions . Matrix-assisted laser desorption ionization time-of-flight mass spectrometry of tryptic peptides derived from the 20 kDa fragment confirmed that this fragment contained a portion of the amino terminal region of MG2 . The present study showed that the N-terminal region of MG2 and a subdomain within this region are microbicidal against A . actinomycetemcomitans and that a 20 kDa fragment of MG2 occurs in whole saliva . This suggests that cleavage of MG2 in vivo may produce fragments with microbicidal properties and that this may represent a novel mechanism of host defense. Expert Opin Ther Targets, 2002 Dec, 6(6), 691 - 7 The situation on antimicrobial agents and chemotherapy in 2002: highlights of the 42nd ICAAC; Giglione C et al.; The 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy took place in San Diego on 27-30 September 2002 . The meeting was held in the light of current events . Bioterrorism, malaria, issues of surveillance and multiple resistance were discussed in depth . Few truly new drugs or potential targets were presented . Peptide deformylase inhibitors and several other metalloenzymes as new targets were among the most promising results. Ann Fr Anesth Reanim, 2002 Oct, 21(8), 634 - 42 {Evaluation of practices in surgical antimicrobial prophylaxis in the Franche-Comté before and after implementation of an information program}; Lallemand S et al.; OBJECTIVES: To assess the practices of surgical antimicrobial prophylaxis in the Franche-Comte region of France before and after the implementation of information program . STUDY DESIGN: Prospective multicenter transversal study type before/after . The information program included a feedback on the observed results during the period before and a meeting with opinion leaders . PATIENTS AND METHODS: Data were collected by 28 pairs of surgeons/anaesthetists . Prescriptions were analysed to answer five questions about antibiotic prophylaxis practices in surgery: did the surgical procedure require antibiotic prophylaxis and was this carried out? Was the appropriate antibiotic used? Was the timing of the first injection optimal? Was the total duration of the treatment correct? Was the dose correct? Our data were compared to national recommendations (updated in 1999) . RESULTS: The overall frequency of conformity was about 40% both before and after the implementation of an information/awareness campaign . Only the conformity of the total duration of the prophylaxis was significantly higher after the action, but only for interventions that lasted less than two hours . {RR = 2.09 (1.32-3.31), p = 0.001} . This improvement in the total duration of regulation seemed to be related to the more frequent use of written protocols in the surgical units . CONCLUSION: Our study confirms that information campaign have little effect within the framework of the good use of antibiotics . We agree with the experts who claim that only an overall strategy including organization, education and restriction will really improve the frequency of conformity of the practices of surgical prophylaxis. Clin Infect Dis, 2002 Dec 15, 35(12), 1491 - 7 Epub 2002 Dec 02. The effect of renal dysfunction on antimicrobial use measurements; Zagorski BM et al.; The defined daily dose, a popular measurement of antimicrobial use, may underestimate the use of antimicrobials that are dose-adjusted in patients with renal insufficiency . To evaluate the effect of renal dysfunction on these measures, we performed a retrospective cohort study that involved patients receiving ceftriaxone, levofloxacin, or vancomycin, with use of defined daily doses and 2 methods based on therapy duration--stop-start days (i.e., entire therapy duration) and transaction days (i.e., unique therapeutic days) . The vancomycin use rate for patients with renal insufficiency was 36% lower than that of patients with normal renal function for defined daily doses, and it was 23% lower for transaction days; for levofloxacin, there was a 27% rate reduction for the defined daily dose . No significant reduction was noted when the stop-start day method was used . Compared with the defined daily dose method, measures of therapy duration are less affected by renal function and may improve comparisons between populations. Rev Saude Publica, 2002 Oct, 36(5), 598 - 606 Epub 2002 Dec 02. {Anticaries effectiveness of fluoride toothpaste: a meta-analysis}; Chaves SC et al.; OBJECTIVE: To carry out a meta-analysis on the effectiveness of fluoride toothpaste for reducing dental caries to calculate the effect size of different hypothesis . METHODS: MEDLINE and LILACS databases were studied in the period from 1980 to 1998 . To evaluate the quality of the studies, methodological rigor criteria proposed by Kay & Locker (1996) were applied after the criteria were submitted to an expert committee of CNPq (National Scientific Council of Brazil) senior researchers . Of 43 papers selected, 22 met the proposed criteria . The effect size of intervention was calculated from differences among the groups and the overall effect of five groups of hypothesis . RESULTS: The high concentration of fluoride in the toothpaste is associated with a larger effect (overall effect = -0.17 CI 95% -0.22/-0.12) . The largest caries reductions were observed when comparing fluoride toothpastes and no fluoride toothpastes (overall effect = -0.29 IC 95% -0.34/-0.24) . The addiction of antimicrobial agents (overall effect = -0.03 IC 95% -0.07/+0.02), differences in abrasive systems (overall effect = -0.02 IC 95% -0.09/+0.04) and active components do not increase the effectiveness of fluoride toothpastes (overall effect = -0.04 IC 95% -0.10/+0.01) . CONCLUSIONS: The highest caries reductions were seen in studies where there was supervised tooth brushing . This review reinforced the importance of tooth brushing with fluoride toothpastes for controlling dental caries . However it showed the emphasis put on medical approaches for disease control rather than specific educational actions . The heterogeneity of the results shows the need to consider issues such as the scenario for implementing preventive methods in the evaluation process. Rev Saude Publica, 2002 Oct, 36(5), 553 - 8 Epub 2002 Dec 02. {Trends in antimicrobial utilization in a university hospital, 1990-1996}; de Castro MS et al.; OBJECTIVE: There is a worldwide concern about rational drug use, more specifically related to antimicrobial utilization . In developing countries, few resources are intended for monitoring on rational drug use . Moreover, there are limited data on the use of antimicrobial agents in hospitals . A study was carried out to describe patterns of use of antimicrobial agents over a 7-year period (1990 to 1996) . METHODS: The study was conducted in a 690-bed tertiary care university hospital in Porto Alegre, Brazil . Hospital records were reviewed to identify inpatient antibiotics use . Results were expressed in defined daily dose per 100-beds/day . Cluster analysis was performed to determine the trends in use of individual agents . RESULTS: Antimicrobials use increased year after year, from 83.8 DDD per 100 beds-day in 1990 to 124.58 DDD per 100 beds-day in 1996 . Penicillins were the drug group mostly used (39.6%), followed by cephalosporins (15.0%), aminoglycosides (14.4%), sulfonamides (12.8%), glycopeptides (3.6%), and lincosamides (3.1%) . These groups were responsible for around 90% of all agents used . The use of antimicrobial agents was divided into thirteen groups based on cluster analysis . CONCLUSIONS: Antimicrobial use increased dramatically in the study period, and this increase was significantly higher when compared to other studies . When newer alternative agents became available in the hospital, the use of already existing drugs decreased and in some cases remained relatively stable . After implementing specific interventions, such as an effort for the correct use of cefoxitin, the expected changes in use were observed. Curr Opin Chem Biol, 2002 Dec, 6(6), 799 - 804 Antimicrobial peptides from amphibian skin: an expanding scenario; Rinaldi AC; Many organisms employ antimicrobial peptides to fend off microbial pathogens . Amphibian skin is one of the most generous sources of these peptides . In the past couple of years, intriguing additional insights on various aspects of frog skin peptides have been reported . Several novel molecules, often with unprecedented structural features, have been discovered . Studies focusing on the factors that regulate the in vivo synthesis of skin peptides in response to infection have gained in prominence . Moreover, recent results indicate new possibilities for the development of effective human therapeutics based on antimicrobial peptides and partially disclosed the biotechnological potential of these molecules. Hybrid Hybridomics, 2002 Oct, 21(5), 359 - 63 Characterization of rat monoclonal antibodies against human beta-defensin-2; Kurosawa S et al.; Defensins are a family of cationic antimicrobial peptides that participate in host defense . Human beta-defensin (hBD)-2 has a potent bactericidal activity against a wide spectrum of microorganisms . Because human gingival epithelium is constantly exposed to a variety of microbial challenges, it is considered that hBD-2 has an important role in the protective mechanisms against oral bacterial infection . However, little is known about the production of hBD-2 in tissues of the oral cavity . Six rat monoclonal antibodies (MAbs) raised against chemically synthesized hBD-2 have been characterized . Rat MAbs were specific for the conformational epitopes on hBD-2, but not to hBD-1 . To identify the epitope on hBD-2, a series of six overlapping peptides covering the hBD-2 whole sequence were synthesized and the immunoreactivities of six MAbs were examined . The FCPRRYK domain in hBD-2 was recognized by all six MAbs and suggested to be an epitope region . By immunocytochemistry, hBD-2 was localized focally in the epidermis of the human gingival tissue using the MAbs . The MAbs specifically recognized against hBD-2 will be a useful tool to study the functional role of antimicrobial agents and an important asset in the imaging of oral infection processes. Arch Surg, 2002 Dec, 137(12), 1353 - 9; discussion 1359 Epidemiology and prognostic determinants of bloodstream infections in surgical intensive care; Harbarth S et al.; HYPOTHESIS: A set of clinical variables available at the bedside can be used to predict outcome in critically ill patients with bloodstream infection (BSI) . DESIGN: A 3-year retrospective cohort study . SETTING: A surgical intensive care unit in Switzerland . PATIENTS: All patients with BSI were potentially eligible . MAIN OUTCOME MEASURES: Clinical variables, organ dysfunctions, and outcome . RESULTS: Among 4530 admissions to the surgical intensive care unit, 224 clinically significant episodes of BSI were recorded (incidence, 4.9%), with a 28-day fatality of 36% . A total of 110 patients had primary bacteremia, of which 39 (35%) were catheter related . Although gram-positive organisms were the most frequently isolated pathogens (58% {159/275}), they were associated with lower case-fatality (30%) than BSI due to gram-negative bacteria (44%) . Organ dysfunctions associated with the highest risk of death were neurologic dysfunction (hazard ratio {HR}, 6.9; 95% confidence interval {CI}, 3.3-14.5), hepatic dysfunction (HR, 3.9; 95% CI, 2.1-7.4), and disseminated intravascular coagulation (HR, 3.0; 95% CI, 1.5-6.1) . By multivariate analysis, 2 independent predictors of mortality were the APACHE II (Acute Physiology and Chronic Health Evaluation II) score at onset of BSI (HR per 1-point increase, 1.08; 95% CI, 1.04-1.12) and the number of evolving organ dysfunctions (HR, 1.4; 95% CI, 1.2-1.7) . Appropriate antimicrobial therapy was associated with improved outcome (HR, 0.4; 95% CI, 0.2-0.6) . CONCLUSIONS: Bloodstream infection in critically ill patients is a common and frequently fatal condition . Its outcome can be predicted by the severity of illness at onset of BSI and the number of organ dysfunctions evolving thereafter . Appropriate antimicrobial therapy is an important determinant for survival. Nat Genet, 2003 Jan, 33(1), 21 - 2 Epub 2002 Dec 09. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis; Roetto A et al.; Animal models indicate that the antimicrobial peptide hepcidin (HAMP; OMIM 606464) is probably a key regulator of iron absorption in mammals . Here we report the identification of two mutations (93delG and 166C-->T) in HAMP on 19q13 in two families with a new type of juvenile hemochromatosis. J Cereb Blood Flow Metab, 2002 Dec, 22(12), 1399 - 419 Inflammation and infection in clinical stroke; Emsley HC et al.; Stroke has enormous clinical, social, and economic implications, and demands a significant effort from both basic and clinical science in the search for successful therapies . Atherosclerosis, the pathologic process underlying most coronary artery disease and the majority of ischemic stroke in humans, is an inflammatory process . Complex interactions occur between the classic risk factors for atherosclerosis and its clinical consequences . These interactions appear to involve inflammatory mechanisms both in the periphery and in the CNS . Central nervous system inflammation is important in the pathophysiologic processes occurring after the onset of cerebral ischemia in ischemic stroke, subarachnoid hemorrhage, and head injury . In addition, inflammation in the CNS or in the periphery may be a risk factor for the initial development of cerebral ischemia . Peripheral infection and inflammatory processes are likely to be important in this respect . Thus, it appears that inflammation may be important both before, in predisposing to a stroke, and afterwards, where it is important in the mechanisms of cerebral injury and repair . Inflammation is mediated by both molecular components, including cytokines, and cellular components, such as leukocytes and microglia, many of which possess pro- and/or antiinflammatory properties, with harmful or beneficial effects . Classic acute-phase reactants and body temperature are also modified in stroke, and may be useful in the prediction of events, outcome, and as therapeutic targets . New imaging techniques are important clinically because they facilitate dynamic evaluation of tissue damage in relation to outcome . Inflammatory conditions such as giant cell arteritis and systemic lupus erythematosus predispose to stroke, as do a range of acute and chronic infections, principally respiratory . Diverse mechanisms have been proposed to account for inflammation and infection-associated stroke, ranging from classic risk factors to disturbances of the immune and coagulation systems . Considerable opportunities therefore exist for the development of novel therapies . It seems likely that drugs currently used in the treatment of stroke, such as aspirin, statins, and modulators of the renin-angiotensin-aldosterone system, act at least partly via antiinflammatory mechanisms . Newer approaches have included antimicrobial and antileukocyte strategies . One of the most promising avenues may be the use of cytokine antagonism, for example, interleukin-1 receptor antagonist. Magn Reson Imaging, 2002 Oct, 20(8), 611 - 4 Renal malacoplakia: demonstration by MR imaging; Zimina OG et al.; We report herein a case of histologically verified bilateral renal malacoplakia . MRI features were distinctive and include multiple nodules 1-2 cm in diameter that were low in signal on T1, T2 and early and late post gadolinium images with intervening fibrous stroma . Demonstration of renal malacoplakia on MR images may obviate the need for major surgery and rapidly direct patients to appropriate antimicrobial therapy for treatment. Bioorg Med Chem, 2003 Jan 2, 11(1), 35 - 41 Synthesis and antibacterial activity of 5-substituted oxazolidinones; Phillips OA et al.; A series of 5-substituted oxazolidinones with varying substitution at the 5-position of the oxazolidinone ring were synthesized and their in vitro antibacterial activity was evaluated . The compounds demonstrated potent to weak antibacterial activity . A novel compound (PH-027) demonstrated potent antibacterial activity, which is comparable to or better than those of linezolid and vancomycin against antibiotic-susceptible standard and clinically isolated resistant strains of gram-positive bacteria . Although the presence of the C-5-acetamidomethyl functionality at the C-5 position of the oxazolidinones has been widely claimed and reported as a structural requirement for optimal antimicrobial activity in the oxazolidinone class of compounds, our results from this work identified the C-5 triazole substitution as a new structural alternative for potent antibacterial activity in the oxazolidinone class. An Esp Pediatr, 2002 Nov, 57(5), 420 - 5 {Changes in antibiotics prescription in primary care}; Albanil Ballesteros MR et al.; BACKGROUND: Bacterial resistance to antimicrobial drugs constitutes a considerable problem in clinical practice . Overprescribing of these drugs contributes to bacterial resistance and current literature shows a growing interest in the rationalization of antibiotic use . OBJECTIVES: To observe the appropriateness of antibiotic prescriptions to children in an outpatient primary care setting, before and after a critical analysis of prescribing habits was performed . PATIENTS AND METHODS: Children aged 0-4 years attending the outpatient pediatric clinic were surveyed in two different periods: 1997 and 2000 . The number of visits, infectious and respiratory diseases observed, and courses of antibiotics prescribed was determined . RESULTS: A total of 456 children, 2,339 diseases, and 829 antibiotic prescriptions were included . Several differences were observed between the two periods: the number of antibiotic courses administered to each child in one year averaged 2.3 in the first period and 1.5 in the second (p < 0.001) . The number of processes receiving antibiotic prescription decreased from 38.8 % to 31.7 % (p < 0.001) . The appropriateness of the decision to treat increased from 85.1 % to 93.3 % (p < 0.001), and the appropriateness of the antibiotic prescribed increased from 56.3 % to 78.7 % (p < 0.001) . The most frequently diagnosed infectious diseases were common cold, tonsillopharyngitis, otitis and bronchitis . The most frequently prescribed antibiotic drugs were amoxicillin, amoxicillin-clavulanate and V penicillin . CONCLUSIONS: Physicians' knowledge of their own antibiotics prescription profiles with subsequent critical comparative analysis with current literature on the subject can help to modify prescribing habits. Drugs, 2002, 62(18), 2581 - 7 Emerging concepts in periodontal therapy; Greenwell H et al.; Conventional periodontal therapy consists of mechanical scaling and root planing, and surgical treatment . This is still the mainstay of periodontal treatment . Adjunctive antimicrobial treatments, both systemic and local delivery, are becoming more sophisticated and useful in the treatment of recurrent periodontitis . Also very promising are adjunctive treatments that modulate the host response and decrease levels of destructive pro-inflammatory cytokines or matrix metalloproteinases . Smoking is a major risk factor for periodontitis and has a profound impact on the progression of periodontal bone and attachment loss . In the interest of improved periodontal health patients should be encouraged to stop smoking . Finally bacterial endotoxins that stimulate the release of pro-inflammatory cytokines can have systemic effects and may lead to pre-term, low birthweight babies, and cardiovascular diseases such as atherosclerosis, myocardial infarction and stroke . Health professionals need to be cognisant of the effect dental health can have on systemic diseases and refer for treatment when appropriate to ensure that optimum oral and systemic health is achieved for their patients. Org Lett, 2002 Dec 12, 4(25), 4387 - 90 UCS1025A and B, new antitumor antibiotics from the fungus Acremonium species; Agatsuma T et al.; {structure: see text} UCS1025A and B, novel pentacyclic polyketides with an unprecedented furopyrrolizidine skeleton, were isolated from the fungus Acremonium sp . KY4917 . The structures and stereochemistry were elucidated by a combination of two-dimensional NMR and X-ray crystallographic analysis . UCS1025A showed unique chemical equilibria involving three tautomeric isomers and exhibited antimicrobial activity and antiproliferative activity against human tumor cell lines. Ann Transplant, 2002, 7(3), 22 - 7 Experience with ATG short course high dose induction therapy in a series of 112 enteric drained pancreatic transplants; Bonatti H et al.; BACKGROUND: New immunosuppressive protocols and advanced surgical technique resulted in a major improvement in the outcome of pancreatic transplantation . PATIENTS AND METHODS: 112 enteric drained whole pancreas transplants (PTx) performed at the Innsbruck University Hospital between 3.1997 and 10.2001 were retrospectively analysed . Prophylactic immunosuppression consisted of FK506, MMF and steroids . A short course of high dose ATG induction was given additionally . Perioperative antimicrobial prophylaxis consisted of Amoxicillin/Clavulanic (32 PTx), Pipercillin/Tazobactam (68 PTx), quinolones (10 PTx) or macrolide (2 PTx) . 64 patients additionally received fluconazole . RESULTS: Actuarial patient, pancreas and kidney graft survival at one year were 96.4%, 86.7% and 95.3%, surgical complication rate was 28%, rejection rate 40% . Eight grafts were lost due to intraabdominal infection, seven due to rejection . Median perioperative observation days (OD) were 29 (range 14-125), patients were on antibiotics for 68% of OD, and developed fever on 33% of OD . Incidence of CMV infection was 42% (but only five patients developed CMV disease), HSV 24%, intraabdominal infection 22%, UTI 11%, wound infection 9% and pneumonia: 5% . CONCLUSION: ATG short course induction is well tolerated after enteric drained PTx . Infection represents a frequent and at least for IA sepsis serious complication after PTx with enteric drainage. Glia, 2003 Jan, 41(1), 64 - 72 Activation of microglia: a neuroinflammatory role for CAP37; Pereira HA et al.; Recent evidence suggests that inflammation and immune function in the central nervous system (CNS) may play a considerable role in the progression of many neurodegenerative diseases . It is known that microglia, the CNS equivalent of peripheral blood monocytes, may be instrumental in causing neurotoxicity . However, the mediator(s) that activates microglia to produce toxic substances that orchestrate cell death has yet to be elucidated . We have identified a novel inflammatory molecule, cationic antimicrobial protein of molecular weight 37 kDa (CAP37), to the brains of patients dying from Alzheimer's disease . CAP37 is known to be a potent activator and regulator of monocyte function in the systemic circulation . We hypothesize that CAP37, a mediator previously shown to recruit and activate monocytes in the systemic circulation, may also play a role in CNS inflammation by modulating microglial function . Here we demonstrate that CAP37 is a chemoattractant for microglia and that CAP37-treated microglia express class II major histocompatibility antigens and produce proinflammatory cytokines and chemokines . We conclude that CAP37 has the ability to activate microglial cells and suggest that it has the potential to serve as a neuroinflammatory molecule . J Allergy Clin Immunol, 2002 Dec, 110(6), 823 - 31 Biology and clinical relevance of naturally occurring antimicrobial peptides; Gallo RL et al.; Within the last decade, several peptides have been discovered on the basis of their ability to inhibit the growth of potential microbial pathogens . These so-called antimicrobial peptides participate in the innate immune response by providing a rapid first-line defense against infection . Recent advances in this field have shown that peptides belonging to the cathelicidin and defensin gene families are of particular importance to the mammalian immune defense system . This review discusses the biology of these molecules, with emphasis on their structure, processing, expression and function . Current evidence has shown that both cathelicidins and defensins are multifunctional and that they act both as natural antibiotics and as signaling molecules that activate host cell processes involved in immune defense and repair . The abnormal expression of these peptides has also been associated with human disease . Current and future studies are likely to implicate the presence of antimicrobial peptides in several unexplained human inflammatory disorders and to provide novel therapeutic approaches to the treatment of disease. Proc AMIA Symp . 2002;:577-81. Impact of a computerized alert during physician order entry on medication dosing in patients with renal impairment; Oppenheim MI et al.; Computerized assistance to clinicians during physician order entry can provide protection against medical errors . However, computer systems that provide too much assistance may adversely affect training of medical students and residents . Trainees may rely on the computer to automatically perform complex calculations and create appropriate orders and are thereby deprived of an important educational exercise . An alternative strategy is to provide a critique at the completion of an order, requiring the trainee to enter the entire order but displaying an alert if an error is made . While this approach preserves the educational components of order-writing, the potential for errors exists if the computerized critique does not induce clinicians to correct the order . The goal of this study was to determine (a) the frequency with which errors are made by trainees in an environment in which renal dosing adjustment calculation for antimicrobials are done by the system after the user has entered an order, and (b) the frequency with which prompts to clinicians regarding these errors leads to correction of those orders. J Mammary Gland Biol Neoplasia, 2002 Apr, 7(2), 123 - 34 Engineering immunity in the mammary gland; Kolb AF; The major physiological function of milk is the transport of amino acids, carbohydrates, lipids, and minerals to mammalian offspring . However, milk is also a rich collection of antimicrobial substances, which provide protection against pathogenic infections . These molecules safeguard the integrity of the lactating mammary gland, but also provide protection for the suckling offspring during a time when its immune system is still immature . The protective substances can be classified into two categories: 1) nonspecific defense substances, which provide innate immunity, and 2) molecules such as antibodies, which provide adaptive immunity and are directed against specific pathogens . The antimicrobial potency of milk has not been a target for farm animal breeding in the past, and present day ruminants provide suboptimal levels of antimicrobial substances in milk . Altered breeding regimes, pharmacological intervention, and transgenesis can be utilized to improve the antimicrobial properties of milk . Such alterations of milk composition have implications for human and animal health. Sci Total Environ, 2002 Nov 1, 299(1-3), 89 - 95 Antimicrobial residues in animal waste and water resources proximal to large-scale swine and poultry feeding operations; Campagnolo ER et al.; Expansion and intensification of large-scale animal feeding operations (AFOs) in the United States has resulted in concern about environmental contamination and its potential public health impacts . The objective of this investigation was to obtain background data on a broad profile of antimicrobial residues in animal wastes and surface water and groundwater proximal to large-scale swine and poultry operations . The samples were measured for antimicrobial compounds using both radioimmunoassay and liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) techniques . Multiple classes of antimicrobial compounds (commonly at concentrations of > 100 microg/l) were detected in swine waste storage lagoons . In addition, multiple classes of antimicrobial compounds were detected in surface and groundwater samples collected proximal to the swine and poultry farms . This information indicates that animal waste used as fertilizer for crops may serve as a source of antimicrobial residues for the environment . Further research is required to determine if the levels of antimicrobials detected in this study are of consequence to human and/or environmental ecosystems . A comparison of the radioimmunoassay and LC/ESI-MS analytical methods documented that radioimmunoassay techniques were only appropriate for measuring residues in animal waste samples likely to contain high levels of antimicrobials . More sensitive LC/ESI-MS techniques are required in environmental samples, where low levels of antimicrobial residues are more likely. Nutr Rev, 2002 Nov, 60(11), 371 - 4 A possible link between hepcidin and regulation of dietary iron absorption; Wessling-Resnick M; The antimicrobial peptide hepcidin has been implicated in the regulation of iron homeostasis . Hepcidin is theorized to be a key link between body iron stores and the appropriate modulation of dietary iron absorption. J Chemother, 2002 Oct, 14(5), 431 - 43 Methylene Blue--a therapeutic dye for all seasons? Wainwright M, Crossley KB. Since it was first synthesised in 1876, Methylene Blue (MB) has found uses in many different areas of clinical medicine, ranging from dementia to cancer chemotherapy . In addition, MB formed the basis of antimicrobial chemotherapy--particularly in the area of antimalarials--and eventually led to the discovery of the neuroleptic drug families . More recently, the photosensitising potential of MB and its congeners has been recognised, and these are being applied in various antimicrobial fields, especially that of blood disinfection . The range of activities of MB is due to the combination of its simple chemical structure and facility for oxidation-reduction reactions in situ. Curr Drug Targets Infect Disord, 2002 Mar, 2(1), 79 - 83 Clinical development of cationic antimicrobial peptides: from natural to novel antibiotics; Hancock RE et al.; Over the past decade, levels of bacterial resistance to antibiotics have risen dramatically and "superbugs" resistant to most or all available agents have appeared in the clinic . Thus there is a growing need to discover and introduce new drugs . One potential source of novel antibiotics is the cationic antimicrobial peptides, which have been isolated from most living entities as components of their non-specific defenses against infectious organisms . Based on these natural templates, scores of structurally diverse antimicrobial cationic peptides have been designed, manufactured both chemically and biologically, and tested for activity against specific pathogens . A few of these peptide antibiotics have entered clinical trials to date, with mixed success . However, their diverse portfolio of structures, activity spectra, biological activities, and modes of action, provide substantial potential. Curr Drug Targets Infect Disord, 2002 Mar, 2(1), 67 - 78 The macrolide binding site on the bacterial ribosome; Poehlsgaard J et al.; Macrolides are a diverse group of antimicrobials that are widely prescribed in clinical and veterinary medicine . Macrolides inhibit bacterial growth by interacting with the large (50S) subunit of the ribosome and thereby blocking protein synthesis . The liberal application of macrolides and the mechanistically similar lincosamide and streptogramin B compounds has in recent years led to increased prevalence of resistance to these drugs . To counteract this trend and improve the efficacy of treatment, numerous macrolide derivatives have been developed and the latest of these, the ketolides, are now becoming available for clinical use . However, in the on-going battle against resistance pathogens continual improvement of drugs will be necessary, and more efficient means of drug development are required . An indication of how rational drug design might be feasible is offered by the recent crystallographic structures of the bacterial ribosome . These structures give us a view of the macrolide target at previously unseen resolution, enabling us to understand the molecular details of macrolide interaction and resistance, and provide strong clues about potential new drug targets. Curr Drug Targets Infect Disord, 2002 Jun, 2(2), 143 - 60 Aminoglycoside antibiotic resistance by enzymatic deactivation; Smith CA et al.; Acquired resistance to the aminoglycoside family of antibiotics has rendered this large and important family of compounds virtually unusable . Resistance is primarily mediated by three classes of enzymes, typically residing on transposable elements in resistant bacteria . These enzymes, the phosphotransferases, acetyltransferases and adenyltransferases, chemically modify the aminoglycosides, which either interferes with drug transport or the binding of the drug at the site of antibacterial action, the 30S ribosomal subunit . The structures of several members of the aminoglycoside-modifying enzyme family are now known, and it is hoped that through a better understanding of these enzymes, both from a structural and mechanistic view-point, could lead to the development of either rationally-designed novel aminoglycosides, or specific structure-based enzyme inhibitors . Such developments could help to bring these compounds back to the forefront of modern antimicrobial chemotherapy . This review focuses on the structural details of the enzymes whose crystal structures are known and on the implications of these findings for devising novel strategies to overcome resistance to this broad class of antibiotics. Curr Drug Targets Infect Disord, 2002 Sep, 2(3), 235 - 46 Histidine kinase-mediated signal transduction systems of pathogenic microorganisms as targets for therapeutic intervention; Stephenson K et al.; Pathogenic bacteria must be able to sense and respond rapidly to signals emanating from the host environment and use the signals to modulate the expression of genes required for the infection process . Two-component signal transduction systems, and their more complex variants known as phosphorelays, are woven within the fabric of bacterial cellular regulatory processes and are used to regulate the expression of genes involved in the virulence and antibiotic resistance responses of a large number of pathogens of major public health concern . The emergence of strains of pathogenic bacteria that are resistant to multiple antibiotics has driven the search for new targets and/or modes of action for anti-microbial agents . The presence of essential two-component systems in bacteria and the central role that these regulatory systems play in virulence and antibiotic resistance has meant that two-component systems and phosphorelays have been recognized as targets for antimicrobial intervention . This review will discuss the role of these signal transduction pathways in virulence responses and antibiotic sensitivity of pathogenic microorganisms and their potential use as targets for antimicrobial therapy . In addition, the current status on the development of inhibitors specific for two-component systems will be discussed. Curr Drug Targets Infect Disord, 2002 Sep, 2(3), 201 - 16 Strategic targeting of essential host-pathogen interactions in chlamydial disease; Coombes BK et al.; The chlamydiae are obligate intracellular gram-negative bacteria that are exquisitely adapted for exploitation of their hosts and contribute to a wide range of acute and chronic human diseases . Acute infections treated with non-cidal antibiotics can lead to the development of persistent, non-replicating bacteria with the corollary that these persistent (yet viable) chlamydiae can resist eradication by further antimicrobial treatment and cause chronic disease . These findings highlight an urgent need for therapeutics that are effective against persistent infections and call for creative approaches to identify potential drug targets . The C . pneumoniae and C . trachomatis genome projects have greatly expanded our knowledge of chlamydial pathogenesis and have provided an enormous potential for the identification and characterization of unknown genes and potential virulence factors in these bacteria . As intracellular pathogens, chlamydiae rely on host cells for all aspects of their survival, from the initial attachment with host cell membranes, to cellular invasion, acquisition of host cell metabolites and intracellular replication . As such, the molecules participating in interactions with the host could be attractive targets for therapeutic intervention . This review describes recent advances in chlamydial genomics, proteomics and cell biology that have cast light on host-pathogen relations that are essential for chlamydial survival . Using this knowledge, we discuss how strategically interfering with essential interactions between chlamydiae and the host cell could be exploited to develop an innovative, and potentially more relevant arsenal of therapeutic compounds. J Antimicrob Chemother, 2002 Dec, 50(6), 945 - 52 Antibiotic resistance in 1962 invasive isolates of Escherichia coli in 27 Spanish hospitals participating in the European Antimicrobial Resistance Surveillance System (2001); Oteo J et al.; In Europe, antimicrobial resistance of invasive pathogens has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS) . The goal of this study is to analyse the susceptibility data of invasive Escherichia coli collected by 27 Spanish laboratories in 2001 . Each laboratory identified strains and tested their susceptibility using its own methods . To assess the comparability of susceptibility test results, a quality assurance exercise was performed . We report data from 1962 invasive isolates of E . coli: 1959 from blood and three from cerebrospinal fluid, corresponding to the same number of patients . Resistance to ampicillin, co-trimoxazole, ciprofloxacin and gentamicin was found in 58.46%, 32.91%, 17.19% and 6.39% of isolates, respectively . Extended-spectrum beta-lactamase (ESBL) production was detected in 30 strains (1.55%) . Ciprofloxacin resistance was higher in isolates from men and in-patients than in those from women and out-patients (P < 0.001) . Resistance to ampicillin and co-trimoxazole was more widespread in children than in adults: 70.37% versus 57.87% (P = 0.01) and 41.84% versus 32.53% (P = 0.05) . Non-significant differences in resistance to fluoroquinolones were observed between isolates from children (11.1%) and adults (17.54%), despite the fact that fluoroquinolones are not administered to children . Significantly, resistance to non-beta-lactam antibiotics (co-trimoxazole, ciprofloxacin and gentamicin) was more prevalent in ampicillin-resistant strains and ESBL-producing strains than in ampicillin-susceptible strains and non-ESBL-producing strains . Multidrug resistance was present in 13.92% of isolates; the most prevalent phenotype was resistance to ampicillin, co-trimoxazole and ciprofloxacin, which was detected in 59.36% of multiresistant strains and in 8.22% of strains overall. BJU Int, 2002 Dec, 90(9), 933 - 8 Experimental Escherichia coli epididymitis in rats: a model to assess the outcome of antibiotic treatment; Ludwig M et al.; OBJECTIVE: To assess the effect of initial antimicrobial therapy with a new highly potent quinolone (sparfloxacin) on the outcome of infection, especially acute and chronic inflammation, in a rat model of unilateral Escherichia coli epididymitis . MATERIALS AND METHODS: The study included 60 Sprague-Dawley rats, each of which received 0.1 mL of an E . coli (0:6 strain) suspension (106 colony forming units/mL) injected into the right ductus deferens . At 24 h after infection an oral antimicrobial treatment with sparfloxacin was initiated in half of the animals . The rats were killed 14 days, 3 and 6 months after infection, and both epididymes and the prostate gland cultured to re-isolate E . coli . To evaluate the grade of inflammation in both epididymes, histological variables, including acute and chronic inflammation and scar formation, were evaluated and a total inflammatory score, representing the sum of all variables, computed . RESULTS: Whereas antimicrobial therapy eradicated the pathogen, in untreated animals the pathogen was detectable for up to 6 months after infection in the infected epididymis and/or the prostate gland, while the contralateral epididymis was sterile . The inflammatory reaction in the infected epididymis was significantly less in treated animals (P < 0.001) . Subclinical nonbacterial inflammation was present in the contralateral epididymis . CONCLUSIONS: Although adequate antimicrobial treatment eradicated the pathogen and reduced the grade of epididymal damage, inflammation was not avoided . Subclinical inflammation of the contralateral epididymis may contribute to impaired fertility . These results indicate that an inflammatory reaction initiated by bacteria might persist as a nonbacterial process despite early therapy, or by bacteria undetectable by conventional culture techniques, and may compromise male fertility. Bull Exp Biol Med, 2002 Aug, 134(2), 156 - 8 Effects of horseradish root on functional activity of phagocytes, total blood cell count, and state of the liver in mice with experimental leprosy; Maslov AK et al.; Therapy of experimental leprosy with dried and grated horseradish root administered perorally in a dose of 300 mg/kg mixed food and treatment with purified horseradish peroxidase increased myeloperoxidase activity of blood neutrophils, enhanced antimicrobial functions of phagocytes, decreased leukocytosis, normalized total blood cell count, and produced no adverse effects on the functional state of the liver in mice. FEBS Lett, 2002 Dec 4, 532(1-2), 115 - 20 Interaction of hagfish cathelicidin antimicrobial peptides with model lipid membranes; Basanez G et al.; Hagfish intestinal antimicrobial peptides (HFIAPs) are a family of polycationic peptides exhibiting potent, broad-spectrum bactericidal activity . In an attempt to unravel the mechanism of action of HFIAPs, we have studied their interaction with model membranes . Synthetic HFIAPs selectively bound to liposomes mimicking bacterial membranes, and caused the release of vesicle-encapsulat