Bactericidal

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-encapsulated fluorescent markers in a size-dependent manner . In planar lipid bilayer membranes, HFIAPs induced erratic current fluctuations and reduced membrane line tension according to a general theory for lipidic pores, suggesting that HFIAP pores contain lipid molecules . Consistent with this notion, lipid transbilayer redistribution accompanied HFIAP pore formation, and membrane monolayer curvature regulated HFIAP pore formation . Based on these studies, we propose that HFIAPs kill target cells, at least in part, by interacting with their plasma membrane to induce formation of lipid-containing pores . Such a membrane-permeabilizing function appears to be an evolutionarily conserved host-defense mechanism of antimicrobial peptides.

J Antibiot (Tokyo), 2002 Sep, 55(9), 794 - 800
Endophenazines A-D, new phenazine antibiotics from the arthropod associated endosymbiont Streptomyces anulatus . I . Taxonomy, fermentation, isolation and biological activities; Gebhardt K et al.; Four new members of the phenazine family, endophenazines A-D, and the already known phenazine-1-carboxylic acid (tubermycin B) were detected in the culture broth of various endosymbiotic Streptomyces anulatus strains by chemical screening in a combination of TLC-staining reagents and HPLC-diode array analysis . The endosymbiotic strains were isolated from four different arthropod hosts at various sites . The new phenazine compounds showed antimicrobial activities against Gram-positive bacteria and some filamentous fungi, and herbicidal activity against Lemna minor (duckweed).

Pharm Res, 2002 Nov, 19(11), 1689 - 95
Enhanced permeability of the antimicrobial agent 2,5-bis(4-amidinophenyl)furan across Caco-2 cell monolayers via its methylamidoidme prodrug; Zhou L et al.; PURPOSE: DB75 {2.5-bis(4-amidinophenyl)furan} is a promising antimicrobial agent although it has poor oral potency . In contrast, its novel prodrug, 2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime (DB289) . has excellent oral potency . The mechanisms of transport of DB289 and DB75 across intestinal epithelium have been investigated in these studies to understand differences in their oral potency . METHODS: Caco-2 cell monolayers were used as an in vitro model to examine the mechanisms of transport of DB289 and DB75 . Samples collected from the transport studies were quantified using high-performance liquid chromatography with ultraviolet and fluorescence detection . RESULTS: A low permeability coefficient (3.8 x 10(-7) cm/s for transport in apical {AP} to basolateral {BL} direction) and high sensitivity to extracellular Ca2+ suggest that AP to BL transport of DB75 across Caco-2 cell monolayers occurs predominantly via a paracellular route . DB289 has an 85-fold higher transport rate (322.0 x 10(-7) cm/s for transport in the AP to BL direction) across Caco-2 monolayers than that of DB75 . This, with its insensitivity to extracellular Ca2+ indicates that AP to BL transport of DB289 across Caco-2 cell monolayers occurs predominantly via a transcellular route . CONCLUSIONS: DB75 is transported across Caco-2 cell monolayers predominantly via paracellular pathways, whereas the prodrug DB289 is transported via transcellular pathways . This could account for the much higher oral activity of DB289 over DB75.

Phytother Res, 2002 Dec, 16(8), 727 - 31
Antibacterial and antifungal activity of essential oils of Mentha suaveolens; Oumzil H et al.; The essential oils (EO) of Mentha suaveolens, a wild Labiatae, which grows in several regions in Morocco, were characterized and their antimicrobial activity assessed . The main aromatic constituents of this plant, as characterized by IR, NMR and MS studies, were pulegone, piperitenone oxide (PEO) and piperitone oxide (PO) occurring in different amounts depending on the subspecies . These constituents as well as a series of other aromatic products such as carvone, limonene and menthone, were tested for their antimicrobial activity against 19 bacteria including Gram-positive and Gram-negative and against three fungi, using solid phase and microtitration assays . Pulegone-rich essential oil inhibited efficiently all the micro-organisms tested with MICs ranging between 0.69 and 2.77 ppm . Among the components from Mentha suaveolens EO, pulegone was the most effective against the tested microorganisms, followed by PEO and PO . The structure-activity relationship is discussed on the basis of the activity of the other aromatic derivatives tested such as carvone, limonene, menthone and the profile of the essential oils of Mentha suaveolens was compared with other Mentha species .

Phytother Res, 2002 Dec, 16(8), 723 - 6
Composition and antimicrobial activity of the essential oil of Ballota pseudodictamnus L . Bentham; Couladis M et al.; The chemical composition of the essential oil of Ballota pseudodictamnus obtained from the aerial parts was analysed by GC/MS . From the 52 identified constituents of the oil, caryophyllene oxide, phytol and gamma-muurolene were the major components . Furthermore, the essential oil was investigated for its antimicrobial activity .

Protein Eng, 2002 Sep, 15(9), 763 - 9
Production and characterization of recombinant tachycitin, the Cys-rich chitin-binding protein; Suetake T et al.; Tachycitin is an invertebrate chitin-binding protein with an amidated C-terminus, and possesses antimicrobial activity against both fungi and bacteria . The (1)H-NMR-based tertiary structure of tachycitin was recently determined {Suetake et al . (2000) J . Biol . Chem., 275, 17929-17932} . In order to examine the structural and functional features of tachycitin more closely, we performed for the first time, gene expression, refolding, (15)N-NMR-based characterizations, and antimicrobial activity measurements of a recombinant tachycitin (rTcn) that does not have the amide group at the C-terminus . The NMR analysis indicated that rTcn possesses the same structural construction as the native tachycitin . The backbone (15)N relaxation measurements showed that the molecular motional correlation time of rTcn increases as its concentration increases, indicating that tachycitins have a tendency to aggregate with each other . rTcn exhibits antimicrobial activity against fungi but not against bacteria . The cell surface of fungi contains chitin as an essential constituent, but that of bacteria does not . These results suggest that not only the chitin-binding region but also the C-terminal amide group of tachycitin plays a significant role in its antimicrobial properties.

EMBO J, 2002 Dec 2, 21(23), 6330 - 7
A serpin mutant links Toll activation to melanization in the host defence of Drosophila; Ligoxygakis P et al.; A prominent response during the Drosophila host defence is the induction of proteolytic cascades, some of which lead to localized melanization of pathogen surfaces, while others activate one of the major players in the systemic antimicrobial response, the Toll pathway . Despite the fact that gain-of-function mutations in the Toll receptor gene result in melanization, a clear link between Toll activation and the melanization reaction has not been firmly established . Here, we present evidence for the coordination of hemolymph-borne melanization with activation of the Toll pathway in the Drosophila host defence . The melanization reaction requires Toll pathway activation and depends on the removal of the Drosophila serine protease inhibitor Serpin27A . Flies deficient for this serpin exhibit spontaneous melanization in larvae and adults . Microbial challenge induces its removal from the hemolymph through Toll-dependent transcription of an acute phase immune reaction component.

Contemp Top Lab Anim Sci, 1998 Mar, 37(2), 59 - 63
Use of Chlorine Dioxide for Antimicrobial Prophylactic Maintenance of Cephalic Recording Devices in Rhesus Macaques (Macaca mulatta); Lee G et al.; Cephalic recording cylinders enclosing craniotomy sites are used to facilitate long-term cerebral access in animals used in many disease models . These models can be hampered because infections caused by microbial pathogens can affect underlying central nervous system tissues . Typically, broad-spectrum antibiotic solutions are instilled into the cylinder to maintain asepsis within the chamber . Despite prophylaxis against antimicrobial pathogens, bacterial and mycotic organisms have been cultured from chambers of recording cylinders used in a laboratory colony of rhesus macaques (Macaca mulatta) . In an attempt to develop a more effective maintenance protocol, preparations of chlorine dioxide were evaluated for their ability to control microbial contamination . Chlorine dioxide test solution was infused into the chambers, and samples for microbial culture were collected throughout several months to evaluate microbial efficacy . Although effective against bacterial isolates in vitro, chlorine dioxide solution failed to adequately control these organisms in vivo . However, 1 or 2 infusions of the solution did eliminate mycotic organisms in most macaques . In contrast, antibiotics inhibited bacterial growth, but allowed fungal proliferation . A treatment schedule that alternated the use of antibiotic solutions and chlorine dioxide solution proved to be an effective means of controlling microbial contamination of recording cylinder chambers in this rhesus macaque colony.

Curr Drug Targets Infect Disord, 2001 Aug, 1(2), 125 - 31
The emerging new generation of antibiotic: ketolides; Zhong P et al.; The bacterial ribosome is a target for a variety of drug classes including macrolides . Macrolide antibiotics are primarily used for the treatment of respiratory tract infections . One of the most important features of the macrolide class is the excellent safety profile allowing the drug to be used broadly across all age groups . The emergence of macrolide resistance, especially in S . pneumoniae, threatens the long-term usefulness of macrolide antibiotics . The newly developed ketolide class, including telithromycin and ABT-773, evolved from the macrolide class and displays significant improvements over macrolides while maintaining safety profiles similar to macrolides . The key improvement in antimicrobial spectrum is the in vitro potency against macrolide resistant pathogens, especially S . pneumoniae . This review outlines the key improvements of ketolides over macrolides in terms of in vitro microbiology, as well as the pharmacokinetic and pharmacodynamic profiles and updates the current understanding of drug-ribosome interactions . The application of cutting-edge technology such as ribosome structure-based rational drug design and genetic engineering are also briefly discussed.

Curr Drug Targets Infect Disord, 2001 May, 1(1), 19 - 36
Bacterial ribosomal subunit synthesis: a novel antibiotic target; Champney WS; The continuing increase in antibiotic-resistant pathogenic bacterial has stimulated research on the development of new antimicrobial agents and the identification of new cellular targets . One such target is the sequence of assembly steps required for the formation of bacterial ribosomal subunits . A large number of different protein synthesis inhibitors which affect large subunit function also prevent the 50S particle from being formed in growing cells . These compounds include the macrolide and ketolide antibiotics as well as certain lincosamides, B-type streptogramins and several other structurally unrelated translational inhibitors . This review describes the activities of these compounds as inhibitors of 50S subunit formation . For most of these drugs, their inhibitory effect on particle synthesis is equivalent to their effect on translation . This new target is thus of equal importance to translational inhibition as a mechanism of action of these compounds . Features of the 50S subunit precursor particle as a target for these drugs are described . Finally a model is presented which accounts for this activity and predicts certain features of the substrate for erythromycin methylase activity in inducible cells . Antibiotics which target subunit formation preferentially are predicted to be important bactericidal agents.

J Dent Res, 2002 Dec, 81(12), 845 - 50
Cathelicidin antimicrobial peptides are expressed in salivary glands and saliva; Murakami M et al.; The expression of antimicrobial peptides at epithelial surfaces such as skin, lung, and intestine is thought to provide protection against infection . Cathelicidin antimicrobial peptides are essential for the protection of skin against invasive bacterial infection . To determine if cathelicidins are also present in the oral cavity, we examined the expression of both mRNA and protein in mice and human saliva . The murine cathelicidin (CRAMP) was detected in the adult by reverse-transcription/polymerase chain-reaction (RT-PCR), and in embryonic, newborn, and adult tissues by in situ hybridization and immunohistochemistry . CRAMP mRNA and protein were localized to the salivary glands, specifically in acinar cells of the submandibular gland and palatine minor glands, as well as in lingual epithelium and palatal mucosa . In man, the human cathelicidin LL-37 was detected in human saliva by Western blotting . These results indicate that cathelicidins are present in the salivary system, in some oral epithelia, and in saliva, contributing to broad-spectrum defense of the oral cavity.

Cardiovasc Surg, 2002 Dec, 10(6), 551 - 4
Primary aortoenteric fistula: report of six new cases; van Olffen TB et al.; Primary aortoenteric fistula (PAEF) is defined as a communication between the native aorta and the gastrointestinal tract, in contrast to secondary fistulas, which arise between a suture line of a vascular graft and the intestine . Arteriosclerosis is the predominant cause of PAEF and accounts for more than two-thirds of the cases reported . The pathogenesis is usually based on direct adhesion of a segment of the gastrointestinal tract to an aortic aneurysm, followed by progressive erosion through the bowel wall . The clinical presentation is usually one of intermittent gastrointestinal haemorrhage resulting in lethal exsanguination . Pain in the abdomen, a pulsatile abdominal mass or fever may be present . The choice of various diagnostic procedures is often decided by the clinical presentation . Esophagogastroduodenoscopy, ultrasound and CT scan may be useful in the evaluation of these patients . Current recommendations for repair include debridement of the aneurysmal aorta, repair with an in situ graft and primary repair of the gastrointestinal tract, followed by aggressive antimicrobial therapy . We present six cases of PAEF surgically treated at the St . Radboud Hospital, the Canisius Wilhelmina Hospital in Nijmegen and the Lukas Hospital in Apeldoorn over a period of 15 years.

Phytochemistry, 2002 Dec, 61(7), 729 - 36
Usnic acid; Ingolfsdottir K; Since its first isolation in 1844, usnic acid {2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione} has become the most extensively studied lichen metabolite and one of the few that is commercially available . Usnic acid is uniquely found in lichens, and is especially abundant in genera such as Alectoria, Cladonia, Usnea, Lecanora, Ramalina and Evernia . Many lichens and extracts containing usnic acid have been utilized for medicinal, perfumery, cosmetic as well as ecological applications . Usnic acid as a pure substance has been formulated in creams, toothpaste, mouthwash, deodorants and sunscreen products, in some cases as an active principle, in others as a preservative . In addition to antimicrobial activity against human and plant pathogens, usnic acid has been shown to exhibit antiviral, antiprotozoal, antiproliferative, anti-inflammatory and analgesic activity . Ecological effects, such as antigrowth, antiherbivore and anti-insect properties, have also been demonstrated . A difference in biological activity has in some cases been observed between the two enantiomeric forms of usnic acid . Recently health food supplements containing usnic acid have been promoted for use in weight reduction, with little scientific support . The emphasis of the current review is on the chemistry and biological activity of usnic acid and its derivatives in addition to rational and ecologically acceptable methods for provision of this natural compound on a large scale.

Br J Dermatol, 2002 Dec, 147(6), 1212 - 7
Tea tree oil reduces histamine-induced skin inflammation; Koh KJ et al.; BACKGROUND: Tea tree oil is the essential oil steam-distilled from Melaleuca alternifolia, an Australian native plant . In recent years it has become increasingly popular as an antimicrobial for the treatment of conditions such as tinea pedis and acne . OBJECTIVES: To investigate the anti-inflammatory properties of tea tree oil on histamine-induced weal and flare . METHODS: Twenty-seven volunteers were injected intradermally in each forearm (study and control assigned on an alternating basis) with histamine diphosphate (5 microg in 50 microL) . Flare and weal diameters and double skin thickness were measured every 10 min for 1 h to calculate flare area and weal volume . At 20 min, 25 microL of 100% tea tree oil was applied topically to the study forearm of 21 volunteers . For six volunteers, 25 microL paraffin oil was applied instead of tea tree oil . RESULTS: Application of liquid paraffin had no significant effect on histamine-induced weal and flare . There was also no difference in mean flare area between control arms and those on which tea tree oil was applied . However, mean weal volume significantly decreased after tea tree oil application (10 min after tea tree oil application, P = 0.0004, Mann-Whitney U-test) . CONCLUSIONS: This is the first study to show experimentally that tea tree oil can reduce histamine-induced skin inflammation.

Br J Dermatol, 2002 Dec, 147(6), 1127 - 34
The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa; Marchini G et al.; BACKGROUND: Peptide antibiotics are part of the surface defences against microbial intruders . However, the presence and significance of these innate immune effectors in the skin barrier of the newborn infant have not yet been appreciated . Erythema toxicum neonatorum is an inflammatory skin reaction of unknown aetiology and significance, commonly present in the healthy newborn infant . OBJECTIVES: As peptide antibiotics are upregulated in inflammatory skin disorders, we hypothesized that this also could be the case in erythema toxicum . We also investigated if the vernix caseosa, a cream-like white substance present on the skin of the infant at birth, might contribute to host defences . METHODS: The presence of the human antibacterial peptide LL-37 was investigated by immunohistochemistry and confocal imaging of skin biopsies from four 1-day-old infants with an erythema toxicum rash and four matched newborns without the rash . In addition, we analysed the expression of LL-37 and human beta defensin-1, an antibacterial peptide of epithelial origin, by reverse transcriptase-polymerase chain reaction . Finally, we screened for antibacterial components in vernix material obtained from six healthy newborns by inhibition zone assays . RESULTS: All biopsies from the lesions of erythema toxicum showed a dense, nodular infiltrate with numerous LL-37-expressing cells located in the dermal layer and a clear localization of the peptide within CD15-expressing neutrophils, EG2-expressing eosinophils and CD1a-expressing dendritic cells . LL-37 was also found to be located in CD1a-expressing Langerhans cells and a positive staining for the peptide was seen throughout the whole epidermal layer, both in infants with and without the rash . Skin samples from infants with the rash of erythema toxicum showed a constitutive expression of human beta defensin-1, while the expression of LL-37 seemed to be induced . Furthermore, LL-37 and lysozyme were detected in the protein fractions derived from the vernix caseosa, and these fractions exhibited a clear antibacterial activity . CONCLUSIONS: Peptide antibiotics are present in the vernix caseosa and in the skin of the healthy newborn infant, indicating effective innate immune protection already during fetal and neonatal life.

Ann Pharmacother, 2002 Dec, 36(12), 1833 - 9
Tenfold medication dose prescribing errors; Lesar TS; BACKGROUND: Tenfold errors in medication dosing continue to occur despite being a well-recognized risk, particularly to pediatric patients . Few systematic evaluations of the characteristics and causes of tenfold medication dosage prescribing errors have been performed . OBJECTIVE: To identify and quantify the characteristics of tenfold medication dosage prescribing errors . DESIGN: Evaluation of 200 consecutively detected medication orders with tenfold errors in dosing in a 631-bed tertiary-care teaching hospital . MAIN OUTCOME MEASURES: Type, frequency, characteristics, causes, enabling factors, and potential for adverse effects of tenfold medication dosage prescribing errors . RESULTS: Two hundred cases of tenfold prescribing errors were detected over an 18-month period . Overdoses were prescribed in 61% of the cases and underdoses in 39% of the cases . Ninety (45%) of the errors were rated as potentially serious or severe; 19.5% of the errors ocurred in pediatric patients . Levothyroxine accounted for 19% of all errors . As a class, antimicrobials, cardiovascular agents, and central nervous system agents each accounted for > or =15% of errors . Errors were associated with multiple zeroes in the dose (45%), use of equations or calculations to determine dose (27% total cases, 92.3% of pediatric cases), dose amount less than 1 (25%), and expression of measure conversion (23%) . The tenfold errors were produced by a misplaced decimal point in 87 cases (43.5%), adding an extra zero in 63 cases (31.5%), and omitting a zero in 50 cases (25%) . Factors identified as enabling a tenfold error to be carried out as ordered were a wide dose range for the drug (76.5%), medication ordered and able to be given by injection (42%), ability to give ordered dose as < or =5 solid oral dosage forms (36%), and availability of an oral liquid dose form (15%) . CONCLUSIONS: Prescribing of tenfold medication dose errors is common and is associated with identifiable risk factors . Implementing commonly recommended medication safety processes are likely to reduce risk to patients from such errors . This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors.

J Appl Microbiol, 1997 Feb, 82(2), 240 - 4
Conjugal transfer of plasmids and antibiotic resistance among Escherichia coli isolated from animals in a rural area in Sarawak (Malaysia); Son R et al.; Thirty-six strains of Escherichia coli isolated from animals in Bario, a remote area in Sarawak, Malaysia, were examined for presence of plasmid DNA and their susceptibility to nine antimicrobial agents . Of the total 36 isolates, five bovine and six canine isolates were found to contain plasmid DNA ranging in sizes from 2.6 to 70 kilobases . All were susceptible to chloramphenicol, erythromycin, gentamicin, nalidixic acid and neomycin but resistance to ampicillin (47%), erythromycin (19%), streptomycin (25%) and tetracycline (11%) was observed . Resistance was associated with carriage of a 47 kb (SC98), 70 kb, (SC133) and 56 and 4.6 kb (SC119) plasmids which were transmissible to the Escherichia coli K12 recipient . It is concluded that animals form a potential reservoir of R plasmids carrying E . coli in the study area.

Semin Perinatol, 2002 Oct, 26(5), 379 - 86
Antimicrobial control programs; Kubin CJ; The use of broad spectrum antimicrobials, the emergence of multiresistant organisms, and the hospital drug costs associated with antimicrobials have all driven the need for institutions to develop strategies to control the use of antimicrobials . Formulary restrictions, prior approval mechanisms, treatment guidelines, order forms, stop orders, antimicrobial management teams, computer-assisted decision support tools, antimicrobial rotation, and combinations of these practices have all been evaluated as methods to encourage the appropriate use of these agents . While many programs have been successful in reducing antimicrobial costs without compromising patient care, limited data are available on the impact of these programs on the development of multiresistant organisms, particularly in neonatal intensive care units . The optimal means for controlling the emergence of resistance have yet to be determined, but ongoing surveillance of antimicrobial utilization and susceptibility patterns are necessary to identify opportunities for interventions, maximize patient care, and potentially minimize the development of resistance.

Dent Update, 2002 Oct, 29(8), 382 - 8
Polypharmacy and dentistry: 2 . Interactions with analgesics and antimicrobials; Meechan JG; In the first paper of this short series the principles involved in drug interactions and the influence of polypharmacy on dental local anaesthesia and sedation were discussed . This second paper will concentrate on interactions with analgesics and antimicrobials prescribed in dental practice.

Arch Pediatr Adolesc Med, 2002 Dec, 156(12), 1230 - 4
The effect of rapid respiratory viral diagnostic testing on antibiotic use in a children's hospital; Byington CL et al.; BACKGROUND: Acute viral respiratory disease is the most common reason for pediatric hospitalization in the United States . Viral illnesses may be mistaken for bacterial infection, and antibiotic therapy may be prescribed . Overprescribing of antimicrobials for viral illness is a factor contributing to increasing antimicrobial resistance among bacterial pathogens encountered in pediatrics . OBJECTIVE: To determine if the availability of a rapid diagnostic test for respiratory viruses would affect antibiotic use in a children's hospital . DESIGN: Retrospective medical record review . SETTING: A 232-bed urban children's hospital . PARTICIPANTS: All hospitalized infants and children who underwent rapid testing (SimulFluor Respiratory Screen; Chemicon International Inc, Temecula, Calif) for respiratory viruses by direct fluorescent assay (DFA) during 2 successive winter seasons . MAIN OUTCOME MEASURES: Rates of antibiotic prescribing in DFA-positive and DFA-negative patients during the 2 study periods . RESULTS: During the first winter season, DFA-positive patients had fewer days using intravenous antibiotics (2.4 vs 4, P =.04), fewer days using oral antibiotics (0.25 vs 2.5, P =.04), and fewer discharge prescriptions for oral antibiotics (37% vs 52%, P =.02) when compared with DFA-negative patients . Intravenous antibiotics were initiated less often for DFA-positive patients during the second winter season than during the first (26% vs 44%, P =.008) . CONCLUSIONS: Direct fluorescent assay testing was associated with a decrease in inappropriate antibiotic use . The availability of rapid viral diagnostics is an important tool for decreasing antibiotic prescribing in pediatric patients.

Appl Environ Microbiol, 2002 Dec, 68(12), 5834 - 42
A multiresistant clone of Shiga toxin-producing Escherichia coli O118:{H16} is spread in cattle and humans over different European countries; Maidhof H et al.; Multiresistant Shiga toxin-producing Escherichia coli (STEC) O118:H16 and O118 nonmotile strains (designated O118:{H16}) were detected by examination of 171 STEC isolates for their antimicrobial sensitivity . Of 48 STEC O118:{H16} strains, 98% were resistant to sulfonamide, 96% were resistant to streptomycin, 79% were resistant to kanamycin, 75% were resistant to tetracycline, 67% were resistant to ampicillin, 60% were resistant to chloramphenicol, 48% were resistant to trimethoprim, and 10% each were resistant to gentamicin and nalidixic acid . Nalidixic acid resistance and reduced susceptibility to ciprofloxacin were associated with the mutation gyrA(LEU-83) . The STEC O118:{H16} strains were found to belong to a single genetic clone as investigated by multilocus enzyme electrophoresis and by multilocus sequence analysis of E . coli housekeeping genes . The STEC O118:{H16} strains originated from humans and cattle and were isolated in seven different countries of Europe between 1986 and 1999 . Strains showing multiresistance to up to eight different antimicrobials predominated among the more recent STEC O118:{H16} strains . The genes in parentheses were associated with resistance to kanamycin (aphA1-Ia), chloramphenicol (catA1), tetracycline {tet(A)}, and ampicillin (bla(TEM-1)) . Class 1 integrons containing sulI (sulfonamide resistance), aadA1a (streptomycin resistance), or dfrA1 (trimethoprim resistance)-aadA1a gene cassettes were detected in 28 strains . The bla(TEM-1b) gene was present in 18 of 21 strains that were examined by nucleotide sequencing . Class 1 integrons and bla(TEM) genes were localized on plasmids and/or on the chromosome in different STEC O118:{H16} strains . Hybridization of XbaI-digested chromosomal DNA separated by pulsed-field gel electrophoresis revealed that bla(TEM) genes were integrated at different positions in the chromosome of STEC O118:{H16} strains that could have occurred by Tn2 insertion . Our data suggest that strains belonging to the STEC O118:{H16} clonal group have a characteristic propensity for acquisition and maintenance of resistance determinants, thus contrasting to STEC belonging to other serotypes.

Drug Resist Updat, 2002 Oct, 5(5), 181 - 91
Infectious disease 2001: drug resistance, new drugs; Georgopapadakou NH; The 41st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was held in Chicago on 16-19 December 2001, rescheduled following the tragic events of 11th September . Nonetheless, it attracted thousands of delegates from industry and academia and covered, in over 2200 oral and poster presentations, topics ranging from bioterrorism, microbial pathogenesis and emerging pathogens, to infection control, vaccines, antibiotic resistance and new antimicrobial agents and treatment strategies . Summarized here are highlights on bacterial and fungal drug resistance and on new agents in preclinical and clinical development.

Biochemistry, 2002 Dec 3, 41(48), 14150 - 7
Translocating proline-rich peptides from the antimicrobial peptide bactenecin 7; Sadler K et al.; The intracellular delivery of most peptides, proteins, and nucleotides to the cytoplasm and nucleus is impeded by the cell membrane . To allow simplified, noninvasive delivery of attached cargo, cell-permeant peptides that are either highly cationic or hydrophobic have been utilized . Because cell-permeable peptides share half of the structural features of antimicrobial peptides containing clusters of charge and hydrophobic residues, we have explored antimicrobial peptides as templates for designing cell-permeant peptides . We prepared synthetic fragments of Bac 7, an antimicrobial peptide with four 14-residue repeats from the bactenecin family . The dual functions of cell permeability and antimicrobial activity of Bac 7 were colocalized at the N-terminal 24 residues of Bac 7 . In general, long fragments of Bac(1-24) containing both regions were bactericidal and cell-permeable, whereas short fragments with only a cationic or hydrophobic region were cell-permeant without the attendant microbicidal activity when measured in a fluorescence quantitation assay and by confocal microscopy . In addition, the highly cationic fragments were capable of traversing the cell membrane and residing within the nucleus . A common characteristic shared by the cell-permeant Bac(1-24) fragments, irrespective of their number of charged cationic amino acids, is their high proline content . A 10-residue proline-rich peptide with two arginine residues was capable of delivering a noncovalently linked protein into cells . Thus, the proline-rich peptides represent a potentially new class of cell-permeant peptides for intracellular delivery of protein cargo . Furthermore, our results suggest that antimicrobial peptides may represent a rich source of templates for designing cell-permeant peptides.

Indian J Pediatr, 2002 Oct, 69(10), 905 - 7
Mycotic aneurysm: an uncommon cause for intra-cranial hemorrhage; Bartakke S et al.; Intra-cranial mycotic aneurysms due to an infective process elsewhere in the body constitute an uncommon cause of intra-cranial hemorrhage . The condition carries a grave prognosis . Mycotic aneurysms secondary to infective endocarditis (IE) rarely occur in children . This communication describes a seven-year-old girl who presented with fever and neurological abnormalities . She was diagnosed to have a mycotic aneurysm secondary to IE . Digital subtraction angiography (DSA) confirmed the diagnosis, delineated anatomical details and later detected the complete resolution of the aneurysm following conservative management with intravenous antimicrobial agents.

Eur Respir J, 2002 Nov, 20(5), 1254 - 62
Factors associated with unknown aetiology in patients with community-acquired pneumonia; Ewig S et al.; Despite comprehensive diagnostic work-up, the aetiology of community-acquired pneumonia (CAP) remains undetermined in 30-60% of cases . The authors studied factors associated with undiagnosed pneumonia . Patients hospitalised with CAP and being evaluated by two blood cultures, at least one valid lower respiratory tract sample, and serology on admission were prospectively recorded . Patients who had received antimicrobial pretreatment were excluded . Patients with definite or probable aetiology were compared to those with undetermined aetiology by uni- and multivariable analysis . A total 204 patients were eligible for the study . The aetiology remained undetermined in 82 (40%) patients, whereas a definite aetiology could be established in 89 (44%) and a probable one in 33 (16%) . In multivariable analysis, factors associated with undetermined aetiology included age >70 yrs, renal and cardiac comorbidity, and nonalveolar infiltrates on the chest radiograph . There was no association of undiagnosed pneumonia with mortality . Age and host factors were associated with unknown aetiology of community-acquired pneumonia . Some of these cases may also represent fluid volume overload mimicking pneumonia.

Antonie Van Leeuwenhoek, 2002 Aug, 81(1-4), 353 - 6
Synergism between fungal enzymes and bacterial antibiotics may enhance biocontrol; Woo S et al.; The interactions between biocontrol fungi and bacteria may play a key role in the natural process of biocontrol, although the molecular mechanisms involved are still largely unknown . Synergism can occur when different agents are applied together, and cell wall degrading enzymes (CWDEs) produced by fungi can increase the efficacy of bacteria . Pseudomonas spp . produce membrane-disrupting lipodepsipeptides (LDPs) syringotoxins (SP) and syringomycins (SR) . SR are considered responsible for the antimicrobial activity, and SP for the phytotoxicity . CWDEs of Trichoderma spp . synergistically increased the toxicity of SP25-A or SRE purified from P . syringae against fungal pathogens . For instance, the fungal enzymes made Botrytis cinerea and other phytopathogenic fungi, normally resistant to SP25-A alone, more susceptible to this antibiotic . Pseudomonas produced CWDEs in culture conditions that allow the synthesis of the LDPs . Purified bacterial enzymes and metabolites were also synergistic against fungal pathogens, although this mixture was less powerful than the combination with the Trichoderma CWDEs . The positive interaction between LDPs and CWDEs may be part of the biocontrol mechanism in some Pseudomonas strains, and co-induction of different antifungal compounds in both biocontrol bacteria and fungi may occur.

Antonie Van Leeuwenhoek, 2002 Aug, 81(1-4), 233 - 43
Cell to cell communication by autoinducing peptides in gram-positive bacteria; Sturme MH et al.; While intercellular communication systems in Gram-negative bacteria are often based on homoserine lactones as signalling molecules, it has been shown that autoinducing peptides are involved in intercellular communication in Gram-positive bacteria . Many of these peptides are exported by dedicated systems, posttranslationally modified in various ways, and finally sensed by other cells via membrane-located receptors that are part of two-component regulatory systems . In this way the expression of a variety of functions including virulence, genetic competence and the production of antimicrobial compounds can be modulated in a co-ordinated and cell density- and growth phase-dependent manner . Occasionally the autoinducing peptide has a dual function, such as in the case of nisin that is both a signalling pheromone involved in quorum sensing and an antimicrobial peptide . Moreover, biochemical, genetic and genomic studies have shown that bacteria may contain multiple quorum sensing systems, underlining the importance of intercellular communication . Finally, in some cases different peptides may be recognised by the same receptor, while also hybrid receptors have been constructed that respond to new peptides or show novel responses . This paper provides an overview of the characteristics of autoinducing peptide-based quorum sensing systems, their application in various gram-positive bacteria, and the discovery of new systems in natural and engineered ecosystems.

Arch Pharm (Weinheim), 2002 Nov, 335(9), 403 - 10
Synthesis of some novel quinoline-3-carboxylic acids and pyrimidoquinoline derivatives as potential antimicrobial agents; El-Sayed OA et al.; The synthesis and in vitro antimicrobial evaluation of several quinoline and pyrimidoquinoline derivatives are described . Treatment of 7-substituted quinolin-2(1H)-one-3-carboxylic acids 2a-c with phosphoryl chloride or thionyl chloride gave rise to the 7-substituted 2-chloroquinoline-3-carboxylic acids 3a-c and 7-substituted 2-chloro-3-chlorocarbonylquinolines 5a-c respectively . The 2-chloro function in compounds 3a-c was replaced by 2-aminothiazole or 2-aminopyridine to give 2-(thiazol-2-yl)aminoquinoline-3-carboxylic acids 4a-c or 2-(pyrid-2-yl)aminoquinoline-3-carboxylic acids 4d-f . Treatment of 5a-c with the same heterocyclic amines at room temperature furnished the corresponding 7-substituted 2-chloro-3-heteryl-aminocarbonylquinolines 6a-f . The tetracyclic 9-substituted thiazolo{3', 2':1, 2}-pyrimido{4, 5-b}quinolin-5-ones 7a-c and 10-substituted pyrido{1', 2':1, 2}-pyrimido{4, 5-b}quinolin-6-ones 7d-f were synthesized by heating 5a-c with the heterocyclic amines in toluene or by heating 6a-f under reflux in dimethylformamide . The products were evaluated in vitro for potential antimicrobial activity.

Clin Exp Med, 2002 Nov, 2(3), 125 - 9
Macrophage chemotactic protein-1 and macrophage inflammatory protein-1 alpha induce nitric oxide release and enhance parasite killing in Leishmania infantum-infected human macrophages; Brandonisio O et al.; Chemokines are a group of structurally defined small proteins that act as chemoattractants for leukocytes and are involved in many different biological activities, including leukocyte activation for antimicrobial mechanisms . We studied the effect of the chemokines monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1 alpha on nitric oxide release and parasitocidal ability of peripheral blood-derived human macrophages in vitro infected with Leishmania infantum, zymodeme MON1 . In infected human macrophages, treatment with MCP-1 or MIP-1 alpha significantly enhanced nitric oxide production and leishmanicidal ability, compared with untreated cells, to the same levels induced by interferon-gamma . Both nitric oxide release and parasitocidal ability of macrophages were significantly reduced by addition of L- N(G)monomethylarginine ( L-NMMA), which is a competitive inhibitor of the L-arginine nitric oxide pathway . These data suggest that MCP-1 and MIP-1 alpha mediate macrophage activation for nitric oxide release and subsequent parasite clearance, and thus may play a role in the containment of Leishmania infection.

J Acquir Immune Defic Syndr, 2002 Dec 1, 31(4), 378 - 83
Total lymphocyte count (TLC) is a useful tool for the timing of opportunistic infection prophylaxis in India and other resource-constrained countries; Kumarasamy N et al.; BACKGROUND: In most resource-constrained countries, CD4 cell count testing is prohibitively expensive for routine clinical use and is not widely available . As a result, physicians are often required to make decisions about opportunistic infection (OI) chemoprophylaxis without a laboratory evaluation of HIV stage and level of immunosuppression.OBJECTIVES To evaluate the correlation of total lymphocyte count (TLC), an inexpensive and widely available parameter, to CD4 count . To determine a range of TLC cutoffs for the initiation of OI prophylaxis that is appropriate for resource-constrained settings . METHODS: Spearman correlation between CD4 count and TLC was assessed in patients attending an HIV/AIDS clinic in South India . Positive predictive value (PPV), negative predictive value (NPV), and sensitivity and specificity of various TLC cutoffs were computed for CD4 count <200 cells/mm3 and <350 cells/mm3 . Correlation and statistical indices computed for all patients and for patients dually infected with HIV and active tuberculosis . RESULTS: High degree of correlation was noted between 650 paired CD4 and TLC counts (r = 0.744) . TLC <1400 cells/mm3 had a 76% PPV, 86% NPV, and was 73% sensitive, 88% specific for CD4 count <200 cells/mm3 . TLC <1700 cells/mm3 had a 86% PPV, 69% NPV, and was 70% sensitive, 86% specific for CD4 count <350 cells/mm3 . The cost of a single CD4 count in India is approximately 30 US dollars, whereas the cost of a single TLC is 0.80 US dollars . CONCLUSION: TLC could serve as a low-cost tool for determining both a patient's risk of OI and when to initiate prophylaxis in resource-constrained settings . PPV, NPV, sensitivity, and specificity maximally aggregated at TLC <1400 cells/mm3 for CD4 <200 cell/mm3 and TLC <1700 cells/mm3 for CD4 <350 cells/mm3 . Selection of appropriate TLC cutoffs for prophylaxis administration should be made on a regional basis depending on OI incidence, antimicrobial resistance patterns, and availability of the antimicrobials.

J Bacteriol, 2002 Dec, 184(24), 7013 - 24
Identification and localization of the gene cluster encoding biosynthesis of the antitumor macrolactam leinamycin in Streptomyces atroolivaceus S-140; Cheng YQ et al.; Leinamycin (LNM), produced by Streptomyces atroolivaceus, is a thiazole-containing hybrid peptide-polyketide natural product structurally characterized with an unprecedented 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a 18-member macrolactam ring . LNM exhibits a broad spectrum of antimicrobial and antitumor activities, most significantly against tumors that are resistant to clinically important anticancer drugs, resulting from its DNA cleavage activity in the presence of a reducing agent . Using a PCR approach to clone a thiazole-forming nonribosomal peptide synthetase (NRPS) as a probe, we localized a 172-kb DNA region from S . atroolivaceus S-140 that harbors the lnm biosynthetic gene cluster . Sequence analysis of 11-kb DNA revealed three genes, lnmG, lnmH, and lnmI, and the deduced product of lnmI is characterized by domains characteristic to both NRPS and polyketide synthase (PKS) . The involvement of the cloned gene cluster in LNM biosynthesis was confirmed by disrupting the lnmI gene to generate non-LNM-producing mutants and by characterizing LnmI as a hybrid NRPS-PKS megasynthetase, the NRPS module of which specifies for L-Cys and catalyzes thiazole formation . These results have now set the stage for full investigations of LNM biosynthesis and for generation of novel LNM analogs by combinatorial biosynthesis.

Br J Ophthalmol, 2002 Dec, 86(12), 1412 - 6
Commensal ocular bacteria degrade mucins; Berry M et al.; BACKGROUND/AIMS: Antimicrobial activity in tears prevents infection while maintaining a commensal bacterial population . The relation between mucin and commensal bacteria was assessed to determine whether commensals possess mucinolytic activity, how degradation depends on mucin integrity, and whether mucins affect bacterial replication . METHODS: Bacteria were sampled from healthy eyes and contact lenses from asymptomatic wearers . Intracellular mucins were extracted and purified from cadaver conjunctivas, and surface mucins from extended wear contact lenses . After exposure to bacteria, changes in mucin hydrodynamic volume (proteolytic cleavage) and subunit charge (oligosaccharide degradation) were assayed by size exclusion and ion exchange chromatography . The effect of mucin on bacterial replication was followed for up to 24 hours from the end of incubation with purified ocular mucins . RESULTS: Ocular bacteria decreased the hydrodynamic volume of intracellular and contact lens adherent mucins, irrespective of glycosylation density . A decrease in mucin sialylation was observed after exposure to commensal bacteria . Subunit charge distributions were generally shifted to lesser negative charge, consistent with loss of charged epitopes . Subunits with high negative charge, observed after digesting lightly adhering contact lens mucins with bacteria, suggest preferential cleavage sites in the mucin molecule . The presence of purified ocular mucin in the medium inhibited bacterial growth . CONCLUSION: Bacteria in the healthy ocular surface possess mucinolytic activity on both intact and surface processed mucins, targeted to discrete sites in the mucin molecule . Inhibition of bacterial growth by ocular mucins can be seen as part of the mucosal control of microbiota.

Arch Oral Biol, 2002 Nov, 47(11), 749 - 56
Effects of carbohydrate polymers applicable in saliva substitutes on the anti-Candida activity of a histatin-derived peptide; Ruissen AL et al.; The effects of polymers applicable in saliva substitutes on the anti-Candida activity of the cationic antimicrobial peptide dhvar1 were investigated . Dhvar1 is a derivative of the 14 C-terminal amino acids of histatin 5 . The effects of the following polymers were tested: uncharged hydroxyethylcellulose (HEC), negatively charged xanthan (XG) and three types of negatively charged carboxymethylcellulose (CMC) of identical mass but different degrees of carboxylic acid-group substitution (DS) . The effects were tested at pH 4.0, 7.0 and 8.5 in a killing assay . HEC had no effect at any pH tested; XG and the three types of CMC caused a decrease in activity at increasing concentrations . Within the CMC group, inhibition increased slightly with increasing DS . These results suggest that the reduction in activity associated with these polymers is the result of electrostatic interaction between the positively charged peptides and the negatively charged polymers . In the absence of polymers, no effect of pH was found on the activity of dhvar1 . In the presence of the charged polymers XG and CMC, lowering the pH from 7.0 to 4.0 resulted in a decrease of dhvar1 activity . It was concluded that, with respect to the retention of activity, HEC is the most appropriate polymer for use in combination with dhvar1 . However, for use in saliva substitutes XG seems more suitable because of its rheological properties . If XG or CMC are to be used, their reductive effect on the anti-Candida activity of dhvar1 should be compensated for by increasing the peptide dose.

Eur J Biochem, 2002 Dec, 269(23), 5911 - 20
The effects of ring-size analogs of the antimicrobial peptide gramicidin S on phospholipid bilayer model membranes and on the growth of Acholeplasma laidlawii B; Kiricsi M et al.; We have examined the effects of three ring-size analogs of the cyclic beta-sheet antimicrobial peptide gramicidin S (GS) on the thermotropic phase behavior and permeability of phospholipid model membranes and on the growth of the cell wall-less Gram-positive bacteria Acholeplasma laidlawii B . These three analogs have ring sizes of 10 (GS10), 12 (GS12) or 14 (GS14) amino acids, respectively . Our high-sensitivity differential scanning calorimetric studies indicate that all three of these GS analogs perturb the gel/liquid-crystalline phase transition of zwitterionic phosphatidylcholine (PtdCho) vesicles to a greater extent than of zwitterionic phosphatidylethanolamine (PtdEtn) or of anionic phosphatidylglycerol (PtdGro) vesicles, in contrast to GS itself, which interacts more strongly with PtdGro than with PtdCho and PtdEtn bilayers . However, the relative potency of the perturbation of phospholipid phase behavior varies markedly between the three peptides, generally decreasing in the order GS14 > GS10 > GS12 . Similarly, these three GS ring-size analogs also differ considerably in their ability to cause fluorescence dye leakage from phospholipid vesicles, with the potency of permeabilization also generally decreasing in the order GS14 > GS10 > GS12 . Finally, these GS ring-size analogs also differentially inhibit the growth of A . laidlawii with growth inhibition also decreasing in the order GS14 > GS10 > GS12 . These results indicate that the relative potencies of GS and its ring-size analogs in perturbing the organization and increasing the permeability of phospholipid bilayer model membranes, and of inhibiting the growth of A . laidlawii B cells, are at least qualitatively correlated, and provide further support for the hypothesis that the primary target of these antimicrobial peptides is the lipid bilayer of the bacterial membrane . The very high antimicrobial activity of GS14 against the cell wall-less bacteria A . laidlawii as compared to various conventional bacteria confirms our earlier suggestion that the avid binding of this peptide to the bacterial cell wall is primarily responsible for its reduced antimicrobial activity against such organisms . The relative magnitude of the effects of GS itself, and of the three ring-size GS analogs, on phospholipid bilayer organization and cell growth correlate relatively well with the effective hydrophobicities and amphiphilicities of these peptides but less well with their relative charge density, intrinsic hydrophobicities or conformational flexibilities . Nevertheless, all of these parameters, as well as others, may influence the antimicrobial potency and hemolytic activity of GS analogs.

Funct Integr Genomics, 2002 Nov, 2(6), 259 - 73 Epub 2002 Oct 17.
Probing plant-pathogen interactions and downstream defense signaling using DNA microarrays; Wan J et al.; The interaction between a plant and a pathogen activates a wide variety of defense responses . The recent development of microarray-based expression profiling methods, together with the availability of genomic and/or EST (expressed sequence tag) sequence data for some plant species, has allowed significant progress in the characterization of plant pathogenesis-related responses . The small number of expression profiling studies completed to date have already identified an amazing number of genes that had not previously been implicated in plant defense . Some of these genes can be associated with defense signal transduction or antimicrobial action, but the functional contribution of many others remains uncertain . Initial expression profiling work has also revealed similarities and distinctions between different defense signaling pathways, and cross-talk (both overlap and interference) between pathogenesis-related responses and plant responses to other stresses . Potential transcriptional cis-regulatory elements upstream of co-regulated genes can also be identified . Whole-genome arrays are only now becoming available, and many interactions remain to be studied (e.g . different pathogen species, plant genotypes, mutants, time-points after infection) . Expression profiling technologies, in combination with other genomic tools, will have a substantial impact on our understanding of plant-pathogen interactions and defense signaling pathways.

J Immunol, 2002 Dec 1, 169(11), 6309 - 15
IFN-gamma-induced apoptosis and microbicidal activity in monocytes harboring the intracellular bacterium Coxiella burnetii require membrane TNF and homotypic cell adherence; Dellacasagrande J et al.; IFN-gamma is critical for the protection against intracellular bacteria through activation of the antimicrobial machinery of phagocytes . Coxiella burnetii, the etiological agent of Q fever, is a strictly intracellular bacterium that inhabits monocytes/macrophages . We previously showed that IFN-gamma induced C . burnetii killing by promoting the apoptosis of infected monocytes . We show in this study that IFN-gamma-induced apoptosis of infected monocytes was characterized by a time- and dose-dependent activation of caspase-3 . IFN-gamma-mediated caspase-3 activation and C . burnetii killing depend on the expression of membrane TNF . Indeed, TNF was transiently expressed on the cell surface of infected monocytes a few hours after IFN-gamma treatment . In addition, anti-TNF Abs inhibited IFN-gamma-mediated caspase-3 activation whereas soluble TNF had no effect on infected cells . Concomitantly, IFN-gamma induced homotypic adherence of C . burnetii-infected monocytes . The latter required the interaction of beta(2) integrins with CD54 . When adherence was disrupted by pipetting, by a combination of Abs specific for CD11b, CD18, and CD54, or by an antisense oligonucleotide targeting CD18 mRNA, both cell apoptosis and bacterial killing induced by IFN-gamma were inhibited . Thus, adherence via CD54/beta(2) integrins together with membrane TNF are required to eliminate C . burnetii-infected cells through cell contact-dependent apoptosis . Our results reveal a new component of the antimicrobial arsenal mobilized by IFN-gamma against infection by intracellular bacteria.

Bioorg Med Chem Lett, 2002 Dec 16, 12(24), 3509 - 13
Bioactive 4-substituted-6-methyl-2-pyrones with promising cytotoxicity against A2780 and K562 cell lines; Marrison LR et al.; Bioactive synthetic 4-substituted-6-methyl-2-pyrones are reported . Various 4-substitutents have been incorporated using Pd-catalysed carbon-carbon bond coupling procedures . Preliminary screening of the 2-pyrones against human ovarian carcinoma (A2780) and human chronic myelogenous leukaemia (K562) cell lines show that 4-alkynyl-6-methyl-2-pyrones have excellent potential as anticancer agents . The pyrones demonstrate broad spectrum antimicrobial activities.

J Surg Res, 2002 Nov, 108(1), 107 - 11
Cationic peptides combined with betalactams reduce mortality from peritonitis in experimental rat model; Ghiselli R et al.; The efficacy of cationic peptides combined with betalactams was investigated in a peritonitis rat model . Intraabdominal sepsis was induced in adult Wistar rats via cecal ligation and single puncture . The study included eight drug-treated groups: each of them received intravenous polymyxin-E (1 mg/kg), buforin II (1 mg/kg), imipenem (20 mg/kg), amoxicillin-clavulanate (50 mg/kg), polymyxin-E (1 mg/kg) plus imipenem (20 mg/kg), or amoxicillin-clavulanate (50 mg/kg), and buforin II (1 mg/kg) plus imipenem (20 mg/kg), or amoxicillin-clavulanate (50 mg/kg) . The study included an untreated control group that received intravenous isotonic sodium chloride solution . All compounds significantly reduced the lethality and the number of bacteria in abdominal fluid compared with saline treatment . Among compounds, imipenem showed the highest antimicrobial activity, while buforin II produced the highest reduction in plasma endotoxin and TNF-alpha levels . Overall, buforin II and imipenem association were the most effective therapeutic approach . Data presented here suggest the potential advantages of combining antimicrobial agents and compounds able to neutralize the biological effect of the endotoxin.

Arzneimittelforschung, 2002, 52(10), 773 - 7
Antimicrobial evaluation of some Mannich bases of acetophenones and representative quaternary derivatives; Gul HI et al.; 1-Aryl-3-dimethylamino-1-propanone hydrochlorides Ia-f (series I) as mono-Mannich bases bis(beta-aroylethyl)ethylamine hydrochlorides IIa, IIb, IId, IIe (series II) as bis-Mannich bases, 3-aroyl-4-aryl-1-ethyl-4-piperidinol hydrochlorides (structural isomer of bis derivatives IIIa-e, series III), and some of their representative quaternary salts (Ig, IIIf, IIIg) were synthesized . Antimicrobial activities of the compounds were evaluated against some bacteria and fungi . Series I and III showed antimicrobial activity against gram positive bacteria . All series demonstrated activity against fungi, however, they generally did not affect gram negative bacteria at the concentration range tested (2-64 micrograms/ml) . Quaternisation procedure improved the bioactivity in compound IIIa for antibacterial activity and in compounds IIIa and IIIb for antifungal activity against Trichophyton rubrum and Mycosporium canis . There was no relationship between Hammett values of the aryl substituents and bioactivities in series III . The mono-Mannich bases of series I had better antimicrobial activities than bis-Mannich bases of series II . Compounds Ia, If, IIId had equal and compounds If and IIIf had higher antibacterial activities compared to the reference drug, streptomycin (CAS 57-92-1), against various gram positive bacteria . On the other hand, compounds Ia, IIIa, IIIc, IIIe, IIIf, and IIIg had equal and If, IIId, IIIf, IIIg had higher antifungal activity compared to the reference drug, amphotericin-B (CAS 1397-89-3), against various fungi . To conclude, the compounds of series III, having both marked antifungal and antibacterial activities, may serve as candidate compounds for further studies . Especially compound IIIf may serve as a model compound to develop new agents against dermatophytes.

Curr Gastroenterol Rep, 2002 Dec, 4(6), 471 - 7
Treatment and management of Helicobacter pylori infection; Go MF; Clinical and basic mechanisms of interaction between Helicobacter pylori and its host have been the subject of numerous publications in the past year . Two additional proton pump inhibitors (PPIs), esomeprazole and rabeprazole, have shown effectiveness in H . pylori eradication when combined with amoxicillin and clarithromycin, and esomeprazole has demonstrated its effectiveness with only one daily dose . Other important recent developments worldwide include evidence-based treatment guidelines established at a European consensus meeting, improved accuracy in the urea breath test and the stool antigen test, new recommendations for second-line therapy, and a greater understanding of antimicrobial resistance in treatment failure . In addition, new studies have confirmed that H . pylori infection and use of nonsteroidal anti-inflammatory drugs or aspirin are the major causes of peptic ulcer disease and ulcer bleeding . This paper reviews the results of these studies and their implications for future research.

Z Naturforsch {C}, 2002 Sep-Oct, 57(9-10), 817 - 21
Antimicrobial activity of some Satureja essential oils; Azaz D et al.; The genus Satureja is represented by fifteen species of which five are endemic and Satureja pilosa and S . icarica have recently been found as new records for Turkey . Aerial parts of the Satureja pilosa, S . icarica, S . boissieri and S . coerulea collected from different localities in Turkey were subjected to hydrodistillation to yield essential oils which were subsequently analysed by GC and GC/MS . The main constituents of the oils were identified, and both antibacterial and antifungal bioassays were applied . Carvacrol (59.2%, 44.8%, 42.1%) was the main component in the oils of S . icarica, S . boissieri and S . pilosa, respectively . The oil of S . coerulea contained beta-caryophyllene (10.6%) and caryophyllene oxide (8.0%) as main constituents.

Z Naturforsch {C}, 2002 Sep-Oct, 57(9-10), 801 - 4
Constituents and biological activities from Muehlenbeckia hastulata; Erazo S et al.; Muehlenbeckia hastulata (J . E.Sm.) Johnst . used mainly for its abortive properties was found active for oxytoxic and analgesic activities in a biological activity screening (oxytoxic, analgesic, antimicrobial, cytotoxic and xanthine oxidase assay) . Epicatechin, emodin-8-glycoside and rutin were isolated from the aerial part and the root of the plant.

Biochem Cell Biol, 2002, 80(5), 667 - 77
Tryptophan-rich antimicrobial peptides: comparative properties and membrane interactions; Schibli DJ et al.; The interaction of several tryptophan (Trp)-rich cationic antimicrobial peptides with membranes was investigated . These peptides included tritrpticin, indolicidin, lactoferricin B (Lfcin B), and a shorter fragment of lactoferricin (LfcinB4-9) . The average environment of the Trp residues of these peptides was assessed from their fluorescence properties, both the wavelength of maximal emission as well as the red edge effect . The insertion of the peptides into vesicles of differing composition was examined using quenching of the Trp fluorescence, with both soluble acrylamide and nitroxide-labelled phospholipids as well as by chemical modification of the Trp residues with N-bromosuccinimide . The results were consistent with the Trp side chains positioned mostly near the membrane-water interface . The extent of burial of the Trp side chains appears to be greater in vesicles containing phospholipids with the anionic phosphatidylglycerol headgroup . Leakage of the aqueous contents of liposomes was also measured using the 8-aminonaphthalene-1,3,6-trisulfonic acid--p-xylene-bis-pyridinium bromide assay . Tritrpticin, which demonstrated the greatest red edge shift, also displayed the largest amount of leakage from liposomes . Taken together, the results illustrate that cationic Trp-rich antimicrobial peptides preferentially disrupt large unilamellar vesicles with a net negative charge following their insertion into the interfacial region of the phospholipid bilayer.

Yakugaku Zasshi, 2002 Nov, 122(11), 967 - 73
{Bacteria-selective synergism between the antimicrobial peptides magainin 2 and tachyplesin I: toward cocktail therapy}; Kobayashi S; Magainin 2 and tachyplesin I (T-SS) are membrane-permeabilizing antimicrobial peptides discovered in frog skin and horseshoe crab hemolymph, respectively . They are classified into different secondary structural classes, i.e., alpha-helix and cyclic beta-sheet, respectively . We found that F5W-magainin 2 (MG2) and T-SS showed marked synergistic effects against gram-negative and-positive bacteria without enhancing hemolytic activity as a measure of toxicity . The results of dye-release experiments using liposomes suggested that the selective synergism is mainly due to anionic phospholipid-specific synergism in membrane permeabilization . Furthermore, the cyclic structure of T-SS was found to be necessary for synergism because a linear analogue of T-SS did not show good synergism with MG2 . These novel observations suggest the possibility of development of cocktail therapeutic regimens using combinations of antimicrobial peptides.

Nippon Rinsho, 2002 Nov, 60(11), 2216 - 24
{Recent trend for the development of new antibacterial agents}; Nishino T; Multidrug resistant organisms such as MRSA, PRSP, BLNAR, ESBL-producing K . pneumoniae and VRE have in recent years emerged as significant pathogens in hospitals . In this paper, I describe the recent trend for the development of new antibacterial agents that are active against these multidrug resistant organisms . A number of new cephem and carbapenem antibiotics were identified to have attractive potency against MRSA, PRSP and P . aeruginosa . These beta-lactam antibiotics had high affinity for PBP 2a of MRSA . AM-112 is a novel beta-lactamase inhibitor that has potent activity against class A, B, C and D beta-lactamases . Telithromycin, ABT-773, CP-642959 and A-217213, ketolide antimicrobials, possess several distinguishing features that are important for these microbiological profile . New extended-spectrum fluoroquinolones(BMS-284756, DQ-113, DK-570 k) with improved activity against Gram-positive pathogens have recently licensed for treatment of RTIs . Drug efflux pumps inhibitors are now under basic research.

Nippon Rinsho, 2002 Nov, 60(11), 2126 - 36
{The guideline how to use the antimicrobial agents--the guidance how to use the antimicrobial agents}; Shiba K; In regard to reconsider the way of antimicrobial agent, it has given the guideline which is how to use the antimicrobial agent to be protected the occurrence of drug resistant bacteria and how to use it safety . This writing omit the way of thinking about the proper use, the safety use, and the prevention for hospital acquired infections by this reference . What the proper use for antimicrobial agent is . The basic idea as the proper use for antimicrobial agent is 1 . to heal a patient(individual-defense), 2 . not to increase drug resistant bacteria(group-defense), 3 . to be utilizable for a medical resource mostly . In the choice of antimicrobial agent for the individual situation, we have to think about 1 . (to heal a patient) seriously first, and then, of course, we recognize the point of view for 2 . and 3 . has a good balance in this way.

Nippon Rinsho, 2002 Nov, 60(11), 2079 - 83
{The significance of establishment of NNIS and JNIS, including the nosocomial infection surveillance}; Harihara Y et al.; The nosocomial infection surveillance is regarded as an important modality of nosocomial infection control . In United State the National Nosocomial Infection Surveillance(NNIS) System was established in 1970 by Centers for Disease Control and Prevention(CDC) to create a national nosocomial infections database . The database is used to describe the epidemiology of nosocomial infections, to describe antimicrobial resistance trends, and to produce nosocomial infection rates to use for comparison purposes . In Japan Japanese Nosocomial Infection Surveillance(JNIS) System was made in 1999 by the Japanese Society of Environmental Infections as a modified version of NNIS system . SSI surveillance is mainly performed using JNIS system . SSI surveillance is going to be performed under the guidance of the Ministry of Welfare and Labor.

Clin Infect Dis, 2002 Dec 1, 35(11), 1390 - 6 Epub 2002 Nov 04.
Infected pressure ulcers in elderly individuals; Livesley NJ et al.; Pressure ulcers in elderly individuals can cause significant morbidity and mortality and are a major economic burden to the health care system . Prevention should be the ultimate objective of pressure ulcer care, and it requires an understanding of the pathophysiology leading to pressure ulcers and the means of reducing both intrinsic and extrinsic risk factors . Clinical manifestations are protean, and early recognition requires a low threshold of suspicion . Clinical examination often underestimates the degree of deep-tissue involvement, and its findings are inadequate for the detection of associated osteomyelitis . Microbiological data, if obtained from deep-tissue biopsy, are useful for directing antimicrobial therapy, but they are insufficient as the sole criterion for the diagnosis of infection . Imaging studies, such as computed tomography and magnetic resonance imaging, are useful, but bone biopsy and histopathological evaluation remain the "gold standard" for the detection of osteomyelitis . The goals of treatment of pressure ulcers should be resolution of infection, promotion of wound healing, and establishment of effective infection control.

Sex Transm Dis, 2002 Nov, 29(11), 624 - 7
Quality control of antibiotics before the implementation of an STD program in Northern Myanmar; Prazuck T et al.; BACKGROUND: The ready availability of poor-quality drugs in developing countries leads to treatment failure and, consequently, excess mortality and morbidity . Moreover, the widespread availability of substandard drugs plays a key role in increasing the resistance to antimicrobial drugs.GOAL As a prerequisite to the establishment of a sexually transmitted disease (STD) control program, this study aimed to evaluate the quality of antibiotics recommended for treatment of STDs that were locally available in the capital of a province of Northern Myanmar . STUDY DESIGN: In addition to the hospital pharmacy, we selected at random 5 of the 41 drug sellers and 5 of the 40 general practitioners who sell antibiotics in the city of Myitkyina . Twenty-one marketing products corresponding to nine different antibiotics used for STD treatment were purchased (benzathine benzylpenicillin, benzylpenicillin, ceftriaxone, chlortetracycline, ciprofloxacin, clotrimazole, co-trimoxazole, doxycycline, and erythromycin) . Drugs were sent to France, where they were analyzed according to the WHO guidelines . Drugs were considered to be standard if their dosage remained in the 10% range of the expected value . RESULTS: Among the 21 different specialty products, only three displayed the official "registered" label . Three drugs were expired and the expiration date was not available for six others . One product did not contain the active drug declared (chlortetracycline; Lombisin, Unicorn, China) and did not show any in vitro activity against bacteria . Seven of 21 products (33%) did not contain the stated dosage (1, more than stated dosage; 6, less than stated dosage) . The highest deficit observed was 48% in two products (co-trimoxazole, Yong Fong, Myanmar; benzylpenicillin, China {city and manufacturer unknown}) . The dosage was not available for five drugs . As a result, only 8 of 21 products (38%) did not contain the stated dosage of active drug . CONCLUSION: These findings suggest that public health policies based on national treatment guidelines should rigorously include the monitoring of quality control of available antimicrobial products . In the absence of such measures, specific treatment strategies are likely to fail and to generate drug resistance.

Infect Immun, 2002 Dec, 70(12), 6968 - 75
Attenuation of the virulence of Porphyromonas gingivalis by using a specific synthetic Kgp protease inhibitor; Curtis MA et al.; The Arg- and Lys-gingipains of Porphyromonas gingivalis are important virulence determinants in periodontal disease and may correspond to targets for immune- or drug-based treatment strategies . In this investigation we aimed to determine which of these enzymes represents the most promising molecular target for protease inhibitor-based therapy and to examine the effectiveness of the resultant compound in a murine virulence assay . Isogenic mutants with mutations in rgpA and rgpB (encoding Arg-gingipains) and in kgp (encoding Lys-gingipain) and a double mutant with mutations in rgpA and rgpB were prepared by using P . gingivalis W50 . The virulence of these mutants indicated that Kgp is a promising drug target . Combinatorial chemistry was used to define the optimal substrate of Kgp, and from this information a specific slowly reversible inhibitor with a nanomolar K(i) was designed and synthesized . Growth of P . gingivalis W50 in the presence of this compound resembled the phenotype of the kgp isogenic mutant; in both instances bacterial colonies failed to form pigment on blood agar, and only poor growth was obtained in a defined medium containing albumin as the sole protein source . Furthermore, pretreatment of the wild-type organism with the Kgp inhibitor led to a significant reduction in virulence in the murine assay . These data emphasize the conclusion that Kgp is an important factor for both nutrition and virulence of P . gingivalis and that inhibitors of this enzyme may have therapeutic potential for the control of P . gingivalis infections . Protease inhibitors may be a potentially novel class of antimicrobial agents with relevance to the control of other bacterial pathogens.

Dent Clin North Am, 2002 Oct, 46(4), 665 - 77, viii
Periodontal therapy using local delivery of antimicrobial agents; Niederman R et al.; Antimicrobial agents, systemic and/or local, are thought by some to be effective agents for treating periodontal infections . Here the authors determine the costs and benefits of local delivery agents for treating periodontal disease . Applying this cost-benefit analysis to patient care, however, will depend upon a clinician's expertise and a patient's value system.

Dent Clin North Am, 2002 Oct, 46(4), 623 - 33, vii
Antibiotic therapy--managing odontogenic infections; Swift JQ et al.; Several pharmaceuticals have been developed in the past 10 years that have made a significant impact on the health of the human race . There have been few advances, however, that have proved more efficacious than the pharmacotherapies we have had available for many decades for the treatment of odontogenic infections . Many new antibiotics/antimicrobials have been developed, but none have been determined to be of significant benefit to replace or supplant the use of penicillins for the management of orofacial infections caused by pathogens in and around the oral cavity . Judicious use of antibiotics in conjunction with surgical therapy is the most appropriate method to treat odontogenic infections . Using the antibiotic "du jour," many times promoted by pharmaceutical representatives, results in costly and unnecessary complexity of care . A return to the basics is indicated for the antibiotic management of odontogenic infections.

Antimicrob Agents Chemother, 2002 Dec, 46(12), 3883 - 91
Synthetic peptides that exert antimicrobial activities in whole blood and blood-derived matrices; Yeaman MR et al.; Peptides that exert antimicrobial activity in artificial media may lack activity within blood or other complex biological matrices . To facilitate the evaluation of antimicrobial peptides for possible therapeutic utility, an ex vivo assay was developed to assess the extent and durability of peptide antimicrobial activities in complex fluid biomatrices of whole blood, plasma, and serum compared with those in conventional media . Novel antimicrobial peptides (RP-1 and RP-11) were designed based in part on platelet microbicidal proteins . RP-1, RP-11, or gentamicin was introduced into biomatrices either coincident with, or 2 h prior to, inoculation with an Escherichia coli target organism . Antimicrobial activities of peptides were assessed by quantitative culture 2 h after bacterial inoculation and compared to those of peptide-free and gentamicin controls . In whole blood and homologous plasma or serum, introduction of RP-1 or RP-11 coincident with E . coli was associated with a significant reduction in CFU per milliliter versus the respective peptide-free controls . Moreover, substantial antimicrobial activity remained when RP-1 or RP-11 was placed into whole blood or plasma 2 h prior to E . coli inoculation . These results suggest that the peptides were not rapidly inactivated within these biomatrices . Peptide antimicrobial activities were negatively affected by preincubation in serum or in heat-inactivated serum, compared with those of the respective controls . Peptides RP-1 and RP-11 were consistently effective at lower concentrations in biomatrices than in artificial media, indicating favorable antimicrobial interactions with components of blood or blood fractions . Collectively, these findings support the concept that synthetic peptides can be designed to exert potent antimicrobial activities in relevant and complex biological matrices.

FEBS Lett, 2002 Nov 20, 531(3), 509 - 12
Antimicrobial action of achacin is mediated by L-amino acid oxidase activity; Ehara T et al.; Achacin is an antibacterial glycoprotein purified from the mucus of the giant snail, Achatina fulica Ferussac, as a humoral defense factor . We showed that achacin has L-amino acid oxidase activity and can generate cytotoxic H(2)O(2); however, the concentration of H(2)O(2) was not sufficient to kill bacteria . The antibacterial activity of achacin was inhibited by various H(2)O(2) scavengers . Immunochemical analysis revealed that achacin was preferentially bound to growth-phase bacteria, accounting for the important role in growth-phase-dependent antibacterial activity of achacin . Achacin may act as an important defense molecule against invading bacteria.

FEBS Lett, 2002 Nov 20, 531(3), 459 - 63
Matrix metalloproteinase 2 is involved in the regulation of the antimicrobial peptide parasin I production in catfish skin mucosa; Cho JH et al.; A 19-residue antimicrobial peptide parasin I is generated from histone H2A in the skin mucus of catfish by the action of cathepsin D activated by a procathepsin D-processing enzyme induced upon epidermal injury . Here we report the isolation and characterization of the procathepsin D-processing enzyme in the mucus of wounded catfish . Sequence analysis of the cDNA identified the purified procathepsin D-processing enzyme as matrix metalloproteinase 2 (MMP 2) . By acting as a procathepsin D convertase upon epidermal injury, MMP 2 is involved in the regulation of parasin I production in catfish skin mucosa.

Biochem J, 2003 Feb 15, 370(Pt 1), 121 - 7
An amphibian antimicrobial peptide variant expressed in Nicotiana tabacum confers resistance to phytopathogens; Ponti D et al.; Esculentin-1 is a 46-residue antimicrobial peptide present in skin secretions of Rana esculenta . It is effective against a wide variety of micro-organisms, including plant pathogens with negligible effects on eukaryotic cells . As a possible approach to enhance plant resistance, a DNA coding for esculentin-1, with the substitution Met-28Leu, was fused at the C-terminal end of the leader sequence of endopolygalacturonase-inhibiting protein, under the control of the cauliflower mosaic virus 35S promoter region, and introduced into Nicotiana tabacum . The antimicrobial peptide was isolated from the intercellular fluids of healthy leaves of transgenic plants, suggesting that it was properly processed, secreted outside cells and accumulated in the intercellular spaces . The morphology of transgenic plants was unaffected . Challenging these plants with bacterial or fungal phytopathogens demonstrated enhanced resistance up to the second generation . Moreover, transgenic plants displayed insecticidal properties.

Nat Prod Lett, 2002 Oct, 16(5), 339 - 44
Antimicrobial triterpenes from Debregeasia salicifolia; Akbar E et al.; New triterpene, 3beta-(trans-cinnamoyloxy)-19alpha-hydroxy-urs-12-ene (1) has been isolated from the methanolic fraction of Debregeasia salicifolia, along with uvaol (2), 3beta,19alpha-dihydroxy-urs-12-ene (3), ursolic acid (4), pomolic acid (5), pomolic acid methyl ester (6) and tormentic acid (7) reported for the first time from this species . The compounds (1), (3) and (6) showed significant antimicrobial activity . The structure elucidation was made with the help of extensive 2D NMR spectroscopic techniques.

Med Pregl, 2002 Jul-Aug, 55(7-8), 299 - 304
{Treatment of acute infections of the lower respiratory tract in children}; Roncevic N et al.; INTRODUCTION: Acute respiratory tract infections are the most common childhood diseases . A preschool child suffers up to 5-7 infections of upper airways during a year . Lower airway infections make 5-20% of all respiratory infections . ETIOLOGIC FACTORS: In developed countries, 75% of pneumonias in childhood are of viral etiology, in 15% of bacterial, and in 10% of some other causative agent (mycoplasma, rickettsiae, fungi, parasites) . In developing countries, bacterial pneumonias are present in much higher percentages . TREATMENT: Treatment of respiratory infections includes antimicrobial therapy (causal), relief of symptoms (symptomatic) and conduction of general principles in child treatment . The choice of antimicrobial drug is based on evidence of agents and their sensitivity to antimicrobial drugs, age, patient's condition, previous treatment and possible allergic reactions to the drug . In cases where we cannot provide adequate specimen for microbiologic testing, when these tests do not reveal the agent, or when therapy must be started before the agent is available, we must decide about the therapy, taking in consideration the most frequent agents, and those that would cause the most devastating clinical picture . This therapy can later be modified according to the isolated agent and its sensitivity to the drug . CONCLUSION: Having in mind the incidence and importance of respiratory infections in morbidity and mortality of children, the aim of this article was to show guidelines in treatment of respiratory infections in children . The main point remains that we should take in consideration the individual patient before all.

Rev Med Chil, 2002 Sep, 130(9), 993 - 1000
{Clinical usefulness of blood cultures in hospitalized patients with community-acquired pneumonia}; Diaz A et al.; BACKGROUND: The clinical role of blood cultures (BC) in the management of hospitalized patients with community-acquired pneumonia (CAP) is controversial . AIM: To evaluate the clinical usefulness of blood cultures in CAP . MATERIAL AND METHODS: We prospectively studied 244 immunocompetent adults with two or more BC obtained at admission . The diagnostic yield of BC and its impact on antibiotic therapy were assessed . RESULTS: Mean age (mean +/- sd) of patients was 67 +/- 20 years, 80% had underlying diseases and 29% received antibiotics prior to admission . Hospital length of stay was 10.4 +/- 10 days and global mortality was 7% . The diagnostic yield of BC was only 8.2% (20 patients) . Mortality was significantly higher in patients with positive BC (20%) than in those with negative BC (5.8%) . In only one of the 20 patients with positive BC (0.4% of total study population), attending physicians changed empiric antimicrobial therapy based on these results . CONCLUSIONS: This study confirms that the diagnostic yield of BC in CAP hospitalized patients is low, that mortality in bacteremic patients is high and suggests that clinical usefulness of BC to guide changes on empiric antimicrobial therapy is limited, in part because attending physicians seldom use such information.

J Inorg Biochem, 2002 Nov 25, 92(3-4), 156 - 64
Herbicides interacting with lanthanide(III) and calcium(II) ions: structural and biological similarities of Gd and Ca polymers; Dendrinou-Samara C et al.; In this paper we report the synthesis and characterization of Ca(II), Gd(III) and Ce(III) complexes with chlorophenoxyalkanoic acids, which are commonly used as herbicides . The Gd(III) and Ca(II) complexes were characterized by the typical formulas {Gd(III)(L)(3)(H(2)O)(2).2dmf}(n) and {Ca(L)(2)(MeOH)(2)}(n) {L={2,4-D=2,4-dichlorophenoxyacetic acid, 2,4,5-T=2,4,5-trichlorophenoxyacetic acid, MCPA=2-methyl-4-chlorophenoxy acetic acid and 2,4-DP=2-(2,4-dichlorophenoxy)propanoic acid}} . The crystal structure of the Gd(III) complex with 2,4-D shows that the compound is a one-dimensional polymer with a {Gd(III)(2)(2,4-D)(6)(H(2)O)(4)} dimeric repeat unit and the gadolinium atoms are in a nine-coordination environment, while the crystal structure of the Ca analog shows that it also has a polymeric structure with a {Ca(2)(2,4-D)(4)(CH(3)OH)(4)} dimeric repeat unit and the calcium atoms are in an eight-coordination environment . The gadolinium compound displays three different coordination modes for the carboxylato moiety, bidentate chelate, bidentate double bound and bidentate triple bound, while the calcium compound displays only one, bidentate triple bound . Coordination spheres are completed with oxygens of H(2)O or MeOH molecules, respectively . The complexes were tested against a few common bacteria by minimum inhibitory concentration (MIC) experiments and did not exhibit any antimicrobial action at concentrations up to 1600 microg/ml.

Enferm Infecc Microbiol Clin, 2002 Dec, 20(10), 498 - 502
{Macrolide consumption according to geographic areas in the province of Valladolid}; Pastor E et al.; AIM: In our setting systemic antibiotics comprise one of the most extensively used treatment groups in Primary Care . Among these, the use of macrolides has increased considerably in recent years and has shown variations in consumption according to geographic areas . This work was performed to quantify these variations . METHODS: Information on macrolide consumption in six geographic areas of the providence of Valladolid over 5 years (1996-2000) was compiled through data provided by International Marketing Services . The indicator used was the defined daily dose per 1,000 inhabitants and day . RESULTS: Macrolide consumption varied considerably among the areas studied . Greatest use of the major macrolides (clarithromycin, erythromycin and spiramycin) was observed in the area of Medina del Campo . Use of the remaining active principles in this subgroup of antibiotics showed the following distribution: midecamycin in the city of Valladolid, azithromycin in Area Norte and roxithromycin in Area Sur . CONCLUSIONS: Macrolide consumption showed significant differences according to areas, with some areas showing double the consumption of others . This diversity indicates specific patterns of use of the antimicrobials in this subgroup.

Curr Infect Dis Rep, 2002 Dec, 4(6), 491 - 497
Antimicrobial Use and Resistance; Rubin MA et al.; As antimicrobial use continues to rise, we are experiencing a concomitant rise in the prevalence of antimicrobial resistance . The precise relationship between use and resistance, however, has been challenging to define . Although the selection pressure exerted by antibiotic therapy appears to be the primary force promoting resistance, it is clear that the pathway to resistance is different for various organisms and antimicrobial agents . By understanding the mechanisms by which resistance emerges and spreads, it should be possible to design intervention strategies to slow or halt the process . This review summarizes some of our current understandings about the development and transmission of antibiotic-resistant bacteria, some of the control measures designed to interrupt the process, and how mathematical modeling can help us to better understand these complex pathways.

J Mol Microbiol Biotechnol, 2002 Sep, 4(5), 479 - 87
Development of a positive genetic selection system for inhibition of protein splicing using mycobacterial inteins in Escherichia coli DNA gyrase subunit A; Adam E et al.; An intein-based positive genetic selection system was developed to study protein splicing and to provide a selection system with the potential for finding splicing inhibitors . Inteins can be novel antimicrobial targets when present in essential proteins since blocking splicing would kill the organism . For example, pathogenic mycobacteria encode inteins that interrupt DNA gyrase . The gyrase selection system exploits (1) splicing of inteins out of Gyrase A and (2) the dominant lethal effect of quinolone poisoning of DNA gyrase, which in turn blocks replication . The system was adapted for whole-cell high-throughput screening using green fluorescent protein as an automatable readout of viability . To demonstrate the efficacy of this system, mutations that blocked splicing of the Mycobacterium xenopi Gyrase A intein were isolated . Splicing was then assayed at a second temperature to identify inteins with a temperature-sensitive splicing phenotype . Mutations were mapped onto a structure-based sequence alignment, which led to the rational prediction of a temperature-sensitive splicing mutation . GyrA intein subdomain relationships also provided insight into intein evolution.

Int J Antimicrob Agents, 2002 Nov, 20(5), 361 - 5
Stimulation of microbial autolytic system by tryptic casein hydrolysate; Biziulevicius GA et al.; Antimicrobial activity of a tryptic casein hydrolysate (TCH), its mode of antimicrobial action and its efficacy in treatment using a newborn calf colibacillosis model are described . The antimicrobial activity of TCH activated the autolytic system of the microbial cell and was expressed mathematically as the autolysis activation index . TCH stimulated the autolytic enzyme system of the 19 bacterial and five fungal strains tested . The autolysis activation index for naturally-autolyzing microorganisms was 1.45-22.0 . Autolysis in three bacterial and one fungal strain that did not lyse in the absence of TCH was increased in its presence by 3.9-56.7% showing activation of latent autolysis . The in vivo trials on 800 newborn calves revealed 93.0% therapeutic and 93.5% prophylactic efficacy for TCH . These levels were similar to the 95.0 and 95.5% attained when Fermosorb, an authorized antimicrobial drug, was used.

Dev Cell, 2002 Nov, 3(5), 711 - 22
Sequential activation of signaling pathways during innate immune responses in Drosophila; Boutros M et al.; Innate immunity is essential for metazoans to fight microbial infections . Genome-wide expression profiling was used to analyze the outcome of impairing specific signaling pathways after microbial challenge . We found that these transcriptional patterns can be dissected into distinct groups . We demonstrate that, in addition to signaling through the Toll and Imd pathways, signaling through the JNK and JAK/STAT pathways controls distinct subsets of targets induced by microbial agents . Each pathway shows a specific temporal pattern of activation and targets different functional groups, suggesting that innate immune responses are modular and recruit distinct physiological programs . In particular, our results may imply a close link between the control of tissue repair and antimicrobial processes.

J Leukoc Biol, 2002 Nov, 72(5), 1003 - 10
Inducible expression of an antimicrobial peptide of the innate immunity in polymorphonuclear leukocytes; Tomasinsig L et al.; Epithelia- and leukocyte-associated antimicrobial peptides provide immediate protection against microbial infections by rapidly inactivating potential pathogens . Bac5 is a member of the cathelicidin family of antimicrobial peptides and is stored in the cytoplasmic granules of bovine neutrophils . We investigated the expression of this gene in airway and intestine, and although the gene was not found to be locally expressed in these tissues, a strong Bac5 induction signal was detected by in situ hybridization in neutrophils infiltrating infected lung, consistent with expression of this gene in activated neutrophils . The Bac5 gene was also induced in bovine peripheral neutrophils stimulated with Escherichia coli or purified lipopolysaccharide (LPS) but not in other blood cells and in resting neutrophils . The levels of Bac5 mRNA increased at 12-24 h post-stimulation, and a dose-dependent increase in Bac5 expression was determined in the presence of increasing amounts of LPS . A metabolically labeled product with a molecular weight compatible with that of proBac5 was immunoprecipitated from cell-free media of stimulated neutrophils, suggesting that the newly synthesized polypeptide is released extracellularly . Collectively, these results provide the first evidence that fully differentiated neutrophils are capable of de novo synthesis and secretion of a granule-associated antimicrobial peptide.

Biochim Biophys Acta, 2002 Nov 19, 1601(1), 55 - 63
Antimicrobial peptides and protease inhibitors in the skin secretions of the crawfish frog, Rana areolata; Ali MF et al.; The dorsal skin of the crawfish frog, Rana areolata, is associated with numerous prominent granular glands . Proteomic analysis of electrically stimulated skin secretions from these glands enabled the identification and characterization of eight peptides with antimicrobial and hemolytic activity belonging to the previously identified brevinin-1, temporin-1, palustrin-2, palustrin-3, esculentin-1 (two peptides), and ranatuerin-2 (two peptides) families . The primary structures of the peptides were consistent with a close phylogenetic relationship between R . areolata and the pickerel frog, Rana palustris . Three structurally related cationic, cysteine-containing peptides were identified that show sequence similarity to peptide Leucine-Arginine, a peptide with immunomodulatory and histamine-releasing properties from the skin of the northern leopard frog, Rana pipiens . The skin secretions contained a 61-amino-acid-residue peptide that inhibited porcine trypsin and possessed a 10-cysteine-residue motif that is characteristic of a protease inhibitor previously isolated from the parasitic nematode, Ascaris suum . A 48-amino-acid-residue protein containing eight cysteine residues in the whey acidic protein (WAP) motif, characteristic of elafin (skin-derived antileukoproteinase) and secretory leukocyte protease inhibitor, was also isolated . The data suggest that protease inhibitors in skin secretions may play a role complementary to cationic, amphipathic alpha-helical peptides in protecting anurans from invasions by microorganisms.

Med J Aust, 2002 Nov 18, 177(10), 558 - 62
Chlamydia pneumoniae and cardiovascular disease; Larsen MM et al.; Chlamydia pneumoniae has been detected in atherosclerotic plaques, while seropositivity to this organism confers a slightly increased risk of coronary events . However, no aetiological link has been established; a major difficulty when investigating this link is the lack of a gold standard for diagnosing chronic vessel infection . The outcomes of case-control studies and prospective trials of macrolides in treatment and prevention of cardiovascular disease have been ambiguous but suggest a short-term preventive effect . Whether this is due to the antimicrobial or anti-inflammatory activity of the macrolides is unknown . Larger and longer prospective trials currently under way may provide better insight into the association of C . pneumoniae with cardiovascular disease . At present, there is no justification for treating cardiovascular disease with antibiotics.

J Obstet Gynaecol Res, 2002 Oct, 28(5), 262 - 8
Current status of prophylactic use of antimicrobial agents for cesarean section in Thailand; Liabsuetrakul T et al.; AIMS: To evaluate actual practices and physician reasons for variation in prophylactic use of antimicrobial agents for cesarean section (CS) . METHODS: The study combined a survey of 2726 medical records and an interview of 50 practicing physicians at the obstetric departments of a university, a regional and a general hospital in Songkhla Province, Southern Thailand . RESULTS: Practices that were consistent with systematic reviews were use in 94%, prescription after cord clamping in 86%, and choosing ampicillin in 91%, because physicians believed in the advantages of these practices . Indications for prophylactic use ranged from routine use for all cases to selective use for indicated cases such as ruptured membranes, vaginal examinations, labor, maternal obesity, or unplanned CS . Single-dose practice was varied greatly across hospitals, from 9% to 84% . The reasons given by physicians for a multiple-dose regimen were personal experience in this regimen and belief in its superiority under their local conditions . This practice was less common where the hospital had practice recommendations . CONCLUSIONS: Not all evidence-based knowledge is adopted in practice . The prophylactic use of antimicrobial agents for CS varies among physicians . Past experience and personal beliefs in the limitation of research generalizability are the barriers to such adoption.

Braz Dent J, 2002, 13(3), 155 - 61
In vitro antimicrobial activity of calcium hydroxide pastes and their vehicles against selected microorganisms; Gomes BP et al.; The aim of this study was to investigate in vitro the antimicrobial activity of calcium hydroxide in combination with several vehicles against some microorganisms commonly isolated from root canals . Antimicrobial activity was determined by the agar diffusion method . Stainless-steel cylinders were placed on each inoculated agar medium . The test medicaments and their controls were placed inside the cylinders . The zones of growth inhibition were measured and recorded after incubation for each plate and the results were analyzed statistically (ANOVA) . The in vitro antimicrobial effects of the medications were ranked from strongest to weakest as follows: Ca(OH)2 + CMCP + glycerine, Ca(OH)2 + CMCP, Ca(OH)2 + glycerine, Ca(OH)2 + anesthetic, Ca(OH)2 + saline, Ca(OH)2 + H2O, Ca(OH)2 + polyethyleneglycol . The pastes with oily vehicles showed significantly larger mean zones of inhibition compared to those with aqueous or viscous vehicles . It was concluded that diffusion and antimicrobial activity of calcium hydroxide were affected by the type of vehicle used.

Nihon Kokyuki Gakkai Zasshi, 2002 Aug, 40(8), 644 - 52
{Usefulness of clinical pathway for community-acquired pneumonia as both an educational and a cost-management tool--an intervention study to compare the usefulness of management with a critical pathway to historical control of conventional management}; Aoshima M et al.; To delineate the usefulness of a clinical pathway for community-acquired pneumonia (CAP) as an educational tool as well as a cost management tool, we conducted a prospective controlled trial including a historical control group . Consecutive CAP patients classified under Category 3 of the American Thoracic Society and admitted to our hospital were evaluated . Using the clinical pathway method, 42 patients were managed between April and December 2000 as the intervention group, and 33 patients received conventional management between April and December 1999 as a historical control . For the intervention group, the clinical pathway, which was a time-task matrix formatted with consideration for guidance for disease treatment, laboratory tests, physical examinations, oxygen saturation monitoring, ambulation, diet, education for the patient and clinical outcomes, was implemented . We determined (1) educational effect, measured using reduction of delay caused by physicians; (2) quality of clinical practice, measured using the success rate of the initial antimicrobial therapy and readmission rate; and (3) economic efficacy, measured using health care cost and length of hospital stay . The delay caused by physicians was reduced by 16% in the Intervention Group (5% vs . 21%; p = 0.045) . The success rates of initial antimicrobial therapy in the two groups were similar (85.7% vs . 84.8%) . In the intention-to-treat set, the median value of health care cost was reduced by yen 48,055 (yen 277,460 vs . yen 325,515; p = 0.017) and the median length of a hospital stay was shortened by 3 days (8 vs . 11 days; p = 0.0007) in the Intervention Group . In conclusion, the clinical pathway had an educational effect on physicians regarding the management of hospitalized patients with community-acquired pneumonia as well as on the cost management.

Plant Physiol, 2002 Nov, 130(3), 1288 - 97
Nitric oxide synthase-mediated phytoalexin accumulation in soybean cotyledons in response to the Diaporthe phaseolorum f . sp . meridionalis elicitor; Modolo LV et al.; Phytoalexin biosynthesis is part of the defense mechanism of soybean (Glycine max) plants against attack by the fungus Diaporthe phaseolorum f . sp . meridionalis (Dpm), the causal agent of stem canker disease . The treatment of soybean cotyledons with Dpm elicitor or with sodium nitroprusside (SNP), a nitric oxide (NO) donor, resulted in a high accumulation of phytoalexins . This response did not occur when SNP was replaced by ferricyanide, a structural analog of SNP devoid of the NO moiety . Phytoalexin accumulation induced by the fungal elicitor, but not by SNP, was prevented when cotyledons were pretreated with NO synthase (NOS) inhibitors . The Dpm elicitor also induced NOS activity in soybean tissues proximal to the site of inoculation . The induced NOS activity was Ca(2+)- and NADPH-dependent and was sensitive to the NOS inhibitors N(G)-nitro-L-arginine methyl ester, aminoguanidine, and L-N(6)-(iminoethyl) lysine . NOS activity was not observed in SNP-elicited tissues . An antibody to brain NOS labeled a 166-kD protein in elicited and nonelicited cotyledons . Isoflavones (daidzein and genistein), pterocarpans (glyceollins), and flavones (apigenin and luteolin) were identified after exposure to the elicitor or SNP, although the accumulation of glyceollins and apigenin was limited in SNP-elicited compared with fungal-elicited cotyledons . NOS activity preceded the accumulation of these flavonoids in tissues treated with the Dpm elicitor . The accumulation of these metabolites was faster in SNP-elicited than in fungal-elicited cotyledons . We conclude that the response of soybean cotyledons to Dpm elicitor involves NO formation via a constitutive NOS-like enzyme that triggers the biosynthesis of antimicrobial flavonoids.

Proc Natl Acad Sci U S A, 2002 Nov 26, 99(24), 15614 - 9 Epub 2002 Nov 11.
Targeting the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex as a therapeutic strategy against tuberculosis: Proof of principle by using antisense technology; Harth G et al.; We have investigated the effect of sequence-specific antisense phosphorothioate-modified oligodeoxyribonucleotides (PS-ODNs) targeting different regions of each of the 3032-kDa protein complex (antigen 85 complex) encoding genes on the multiplication of Mycobacterium tuberculosis . Single PS-ODNs to one of the three mycolyl transferase transcripts, added either once or weekly over the 6-wk observation period, inhibited bacterial growth by up to 1 log unit . A combination of three PS-ODNs specifically targeting all three transcripts inhibited bacterial growth by approximately 2 logs; the addition of these PS-ODNs weekly for 6 wk was somewhat more effective than a one-time addition . Targeting the 5' end of the transcripts was more inhibitory than targeting internal sites; the most effective PS-ODNs and target sites had minimal or no secondary structure . The effect of the PS-ODNs was specific, as mismatched PS-ODNs had little or no inhibitory activity . The antisense PS-ODNs, which were highly stable in M . tuberculosis cultures, specifically blocked protein expression by their gene target . PS-ODNs targeting the transcript of a related 24-kDa protein (mpt51) had little inhibitory effect by themselves and did not increase the effect of PS-ODNs against the three members of the 3032-kDa protein complex . The addition of PS-ODNs against the transcripts of glutamine synthetase I (glnA1) and alanine racemase (alr) modestly increased the inhibitory efficacy of the 3032-kDa protein complex-specific PS-ODNs to approximately 2.5 logs . This study shows that the three mycolyl transferases are highly promising targets for antituberculous therapy by using antisense or other antimicrobial technologies.

Microbiology, 2002 Nov, 148(Pt 11), 3737 - 41
Naphthalene, an insect repellent, is produced by Muscodor vitigenus, a novel endophytic fungus; Daisy BH et al.; Muscodor vitigenus is a recently described endophytic fungus of Paullinia paullinioides, a liana growing in the understorey of the rainforests of the Peruvian Amazon . This fungus produces naphthalene under certain cultural conditions . Naphthalene produced by M . vitigenus was identified by gas chromatography/mass spectrometry . Its chromatographic and mass spectral properties were identical to authentic naphthalene . Agar plugs supporting growth of the fungus and producing known amounts of naphthalene effectively repelled the adult stage of the wheat stem sawfly, Cephus cinctus, in Y-tube bioassay tests . Authentic naphthalene, at comparable concentrations to those in tests involving the fungus itself, mimicked the insect repellency of the fungus . Although other Muscodor spp . produce volatile antimicrobials, M . vitigenus is unique in its ability to produce naphthalene almost exclusively . This report also describes the potential practical implications of M . vitigenus.

Clin Microbiol Infect, 2002, 8 Suppl 2, 107 - 28
Moving from recommendation to implementation and audit: part 2 . Review of interventions and audit; Christiansen K et al.; There are multiple interventions available that may help to control the development and spread of resistance to antimicrobial agents in bacteria implicated in community-acquired respiratory tract infections . Unfortunately, very few studies have assessed the effectiveness of these interventions using objective end-points, such as reduction in resistance rates and improvement in clinical outcomes . Most interventions are centered on reducing inappropriate or unnecessary use of antibiotics; others focus on reducing disease burden and bacterial colonization . With regard to antibiotic use, efforts should be concentrated at both the prescriber and consumer levels . Interventions that target prescribers include: provision of educational materials; strategies and tools to improve diagnosis; implementation of practice guidelines; personalized interactive sessions with feedback on the practice profile; and use of delayed prescription and alternative prescribing strategies . Optimal results are usually obtained when these interventions are combined with consumer education . Regulatory interventions (e.g . licensing regulations and controlled access to drugs), restrictions in the use of agents for growth promotion in animals, and use of nonantimicrobial therapies (e.g . probiotics) may help further to reduce inappropriate antibiotic use and thereby decrease the selective pressure for development of resistance . Infection-control strategies, public health measures, vaccination programs, and new antibiotics all have a role in minimizing the spread of resistant organisms . Ideally, resistance-control programs should include predefined criteria for success and integral audit processes based on objective end-points (antibiotic use, resistance trends, and health outcomes) . Standardization of data collection is imperative so that the relative merits of various interventions can be compared . Effective implementation and audit of interventions is often difficult in developing countries owing to poor health-care infrastructures, lack of resources, poor education/training, and minimal regulatory controls on the supply and quality of antimicrobials . Substantial support from governments and health-care organizations across the globe is required to initiate and sustain effective intervention programs to control antimicrobial resistance.

Clin Microbiol Infect, 2002, 8 Suppl 2, 92 - 106
Moving from recommendation to implementation and audit: part 1 . Current recommendations and programs: a critical commentary; Carbon C et al.; Growing concern over the spread of resistance to antibiotics and other antimicrobials has prompted a plethora of recommendations for its control . Strategic programs for resistance containment have been initiated in various countries, particularly in Western Europe and North America . The World Health Organization and the European Union have responded to the need for international action by publishing guidance and encouraging collaboration . These recommendations rightly focus on controlling resistance in the community . They agree on the importance of surveillance of resistance patterns and antibiotic usage and the need to encourage judicious antibiotic usage (especially through education of prescribers and the public) . Yet there remains a pressing need for the implementation of effective actions to address these issues . Important considerations given less attention include infection prevention (e.g . through immunization), the use of rapid diagnostic tests to reduce antibiotic usage, audit of implemented actions, and the provision of feedback . Furthermore, research is necessary to fill the substantial gaps in our knowledge . Notably, the reversibility or containment of resistance with the optimization of antibiotic usage has yet to be definitely established . For now, antimicrobial management programs should focus on ensuring the most appropriate use of antimicrobials rather than simply on limiting choices . Finally, developed countries must recognize that a truly global approach to resistance containment will require greater support for developing countries.

Clin Microbiol Infect, 2002, 8 Suppl 2, 43 - 68
The patient's role in the spread and control of bacterial resistance to antibiotics; Davey P et al.; As the ultimate consumers, patients play an important role in the emergence, spread and control of bacterial resistance to antibiotics . Improved knowledge of antibiotics and the problem of resistance, as well as a better understanding of beliefs, pressures/concerns, and expectations, from both the patient's and physician's perspectives, are fundamental for controlling antibiotic use . There is growing evidence to suggest that empowering patients through implementation of patient-centered health-care strategies, such as shared decision-making, in conjunction with educational initiatives help to change attitudes and behavior, and improve access to and completion of appropriate antimicrobial therapy . This, in turn, may help to control the development and spread of resistance to antibiotics.

Pharm World Sci, 2002 Oct, 24(5), 188 - 95
Survey of drug use practices and antibiotic prescribing pattern at a general hospital in Nigeria; Chukwuani CM et al.; OBJECTIVE: To describe the current drug use practices at the institution, and gather baseline data, which can serve as a basis for designing an appropriate intervention to improve the drug use profile . METHOD: A retrospective audit of in- and out-patient prescriptions, generated during the period January-March 1999 . Indicators of drug use pattern include: average number of drugs prescribed per encounter (ANDPE), average number of antibiotics prescribed per encounter (ANAPE), % encounter with antibiotics (PEA), percent of antibiotic prescriptions based on microbial sensitivity test results (MCST) . Additionally, a "knowledge, attitude and practice" (KAP) survey of prescribers and dispensers was performed . Indicators of prescribing and dispensing quality include: sources of drug/prescribing information, availability and use of the hospital formulary, knowledge of the prescribing process and the adequacy of the drug supply management system . RESULTS: A total of 9984 outpatient prescriptions and 127 in-patient case notes were audited . The total number of prescribers and dispensers surveyed were 88 and 13 respectively . The ANDPE was found to be 3.16 for out-patients and 9.7 for in-patients, ANAPE was 1.1 and 2.4 for out-patients and inpatients respectively . The PEA was 50.3% for out-patients and 96.7% for in-patients . Only 4.2% of in-patient antibiotic prescriptions were based on MCST and percent encounter with switches in antimicrobial therapy was 52.1% while the average number of switches per encounter was 1.35 . In 18.5% of the in-patient encounters there was evidence of drug incompatibilities . The KAP survey revealed that prescribers and dispensers in the hospital rely on different sources for their drug information needs (MIMS vs Martindale Extrapharmacoepia) . None of the prescribers surveyed was able to correctly enumerate all the 4 steps involved in the prescribing process, about 25% got at least 2 steps correctly, and only 9.1% of the dispensers surveyed could accurately define a hospital formulary . The drug supply management system was found to be inadequate . CONCLUSION: The survey revealed that appreciable gaps in knowledge with respect to rational drug use, still exists among these cadre of healthcare professionals . The foregoing suggests an urgent need for review of current policies and systems in the hospital with the view of enhancing the drug use practices of the health providers . Specifically it is recommended that there should be an intervention program involving concerted continuing education (to influence the KAP of the various cadre of healthcare providers) and the establishment of a hospital formulary/standard treatment guidelines.

Pharm World Sci, 2002 Oct, 24(5), 182 - 7
The identification of barriers preventing the successful implementation of a surgical prophylaxis protocol; Burnett KM et al.; AIM: The aim of this study was to introduce a protocol for the use of antimicrobials in surgical prophylaxis for the described procedures in Antrim Area Hospital . METHOD: Historical data of antimicrobial use were obtained from retrospective analysis of patients' charts, for those patients identified as having one of the following 'clean/contaminated' surgical procedures over the previous six months; cholecystectomy or abdominal hysterectomy . These data were analysed, and a protocol was introduced providing guidelines for the choice of antimicrobial agent, its administration time, route, dose, duration and frequency of treatment . MAIN OUTCOME MEASURE: The main outcome measure was the success of the uptake of the protocol following its implementation . RESULTS: There was a total of 285 patients identified, 105 prior to and 180 post implementation . Overall, 68% of patients received some form of prophylaxis in the first cycle, and 72% in the second . CONCLUSION: Although the introduction of the protocol led to slight improvements in compliance with standard prescribing procedures, with an increase in single-dose prophylaxis, and a reduction in prolonged prophylactic treatment, the improvements did not reach expectations . This paper attempts to identify the possible barriers to protocol implementation.

Boll Chim Farm, 2002 Jul-Aug, 141(4), 304 - 10
Synthesis and pharmacological studies of some 2-t-amino and 2,3-di-t-amino substituted 1,4-naphthoquinones and related compounds; Tandon VK et al.; Series of 2-t-amino and 2,3-di-t-amino substituted-1,4-naphthoquinones have been synthesised from corresponding 1,4-naphthoquinones by reaction with secondary amines . The compounds have been evaluated for their broad spectrum antimicrobial, antiviral and anticancer activity . In the preliminary screening results 8a and 9a have shown profile of an antimicrobial agent.

J Biol Chem, 2003 Jan 24, 278(4), 2256 - 64 Epub 2002 Nov 07.
Mitogen-activated protein kinases play an essential role in oxidative burst-independent expression of pathogenesis-related genes in parsley; Kroj T et al.; Plants are continuously exposed to attack by potential phytopathogens . Disease prevention requires pathogen recognition and the induction of a multifaceted defense response . We are studying the non-host disease resistance response of parsley to the oomycete, Phytophthora sojae using a cell culture-based system . Receptor-mediated recognition of P . sojae may be achieved through a thirteen amino acid peptide sequence (Pep-13) present within an abundant cell wall transglutaminase . Following recognition of this elicitor molecule, parsley cells mount a defense response, which includes the generation of reactive oxygen species (ROS) and transcriptional activation of genes encoding pathogenesis-related (PR) proteins or enzymes involved in the synthesis of antimicrobial phytoalexins . Treatment of parsley cells with the NADPH oxidase inhibitor, diphenylene iodonium (DPI), blocked both Pep-13-induced phytoalexin production and the accumulation of transcripts encoding enzymes involved in their synthesis . In contrast, DPI treatment had no effect upon Pep-13-induced PR gene expression, suggesting the existence of an oxidative burst-independent mechanism for the transcriptional activation of PR genes . The use of specific antibodies enabled the identification of three parsley mitogen-activated protein kinases (MAPKs) that are activated within the signal transduction pathway(s) triggered following recognition of Pep-13 . Other environmental challenges failed to activate these kinases in parsley cells, suggesting that their activation plays a key role in defense signal transduction . Moreover, by making use of a protoplast co-transfection system overexpressing wild-type and loss-of-function MAPK mutants, we show an essential role for post-translational phosphorylation and activation of MAPKs for oxidative burst-independent PR promoter activation.

J Ethnopharmacol, 2002 Dec, 83(3), 193 - 9
Healing potential of Datura alba on burn wounds in albino rats; Priya KS et al.; Datura alba Nees (Solanaccae) is popular all over the world for its medicinal uses in asthma, muscle spasm, whooping cough, hemorrhoids, skin ulcers, etc . In India, it is widely used traditionally for the relief of rheumatism and other painful affections . Ayurveda and Siddha practitioners use oil based preparations of this plant from ancient days to till date for all types of wounds . Hence, the present study was chosen to evaluate its scientific validity . The alcohol extract of the D . alba leaves were investigated for the evaluation of its healing efficiency on burn wound models in rats . The crude alcohol extract and one of the fractions exhibited antimicrobial effect against all the pathogens studied . A 10% (w/w) formulation of alcoholic extract was topically applied on thermal wounds . Complete wound closure was observed within 12 days in treated rats . The effect produced by the ointment, in terms of wound contracting ability, wound closure time, tissue regeneration at the wound site and histopathological characteristics were significant in treated rats . Collagen, hexosamine and gelatinase expressions were also well correlative with the healing pattern observed . The present study thus provides a scientific rationale for the traditional use of this plant in the management of wounds.

Enferm Infecc Microbiol Clin, 2002 Nov, 20(9), 431 - 4
{Microbiological factors that influence the eradication of Helicobacter pylori in adults and children}; Domingo D et al.; AIM: To study microbiological factors of Helicobacter pylori, such as antimicrobial susceptibility and virulence, which affect the eradication of the microorganism in gastric mucosa of adult and pediatric patients . METHODS: Fifty-five H . Pylori strains were isolated from culture of biopsy specimens from 39 adult and 16 pediatric patients . Antibiotic susceptibility was determined by agar dilution and study of virulence factors (cagA gene and alleles s1 and s2 of the vacA gene) by PCR . Outcome of treatment with amoxicillin (AMX), clarithromycin (CLR) and omeprazole was assessed by the urea breath test . We studied the relation of minimum inhibitory concentration (MIC) of AMX and CLR and presence of virulence factors with eradication of the microorganism.Results . The eradication rate was 69% (38/55), 71.7% in adults and 62.5% in children . Resistance to CLR and AMX was 14.5% and 0%, respectively . Overall eradication rates with respect to the variables studied were: 75% and 53% in strains with AMX MICs of < or = 0.01 6mg/L and > or = 0.032 mg/L (range < or = 0.008-0.5) (p > 0.05), 79% and 12% in strains with clarithromicina MICs of < 1 mg/L and > or = 1mg/L (range # 0.008-64) (p < 0.05), 79% and 54% in cagA+ and cagA strains (p > 0.05) and 82% and 62% in s1 and s2 strains (p > 0.05), respectively . CONCLUSIONS: H . pylori strains with higher amoxicillin and clarithromycin MICs, and cagA and vacA s2 strains were related with lower rates of eradication in both adult and pediatric populations treated with amoxicillin, clarithromycin and omeprazole.

Respir Care, 2002 Nov, 47(11), 1305 - 12; discussion 1312-3
Formulations and nebulizer performance; O'Riordan TG; To deliver a drug by nebulization, the drug must first be dispersed in a liquid (usually aqueous) medium . After application of a dispersing force (either a jet of gas or ultrasonic waves), the drug particles are contained within the aerosol droplets, which are then inhaled . Some drugs readily dissolve in water, whereas others need a cosolvent such as ethanol or propylene glycol . Some drugs are delivered as suspensions, and the efficiency of nebulizers can be different for solutions and suspensions . Solutions are delivered more efficiently with most devices . In general, conventional ultrasonic nebulizers should not be used to aerosolize suspensions, because of low efficiency . Newer strategies to improve the delivery of non-water-soluble drugs include the use of liposomes and the milling of the drug into very small "nanoparticles." In addition to the active therapeutic ingredient and solvents, drug formulations may include buffers (the solubility of some medications is influenced by pH), stabilizers, and, in the case of multi-dose preparations, antibacterial agents . Though formulations are designed to optimize drug solubility and stability, changes in formulation can also affect inhaled mass, particle size, and treatment time, though the differences between nebulizer brands probably have a greater impact than differences in formulation . Ultrasonic and jet nebulizers may damage protein and other complex agents through heat or shear stress . Additives to multi-dose formulations, especially antimicrobial and chelating agents, may cause adverse events, so there is a trend towards single-use, preservative-free vials.

J Infect Dis, 2002 Dec 1, 186 Suppl 2, S225 - 33
Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury; Scheld WM et al.; No bacterial disease has undergone a more dramatic change in epidemiology during the past decade than acute bacterial meningitis . This review describes the changing epidemiology and considers some important recent observations that contribute to our understanding of the pathogenesis and pathophysiology of meningitis . The major focus is on the mechanisms of neuronal injury and the pathophysiologic concepts responsible for death and neurologic sequelae . In recent years, experimental studies have amplified our understanding of the substantial body of evidence that now implicates cytokines and chemokines, proteolytic enzymes, and oxidants in the inflammatory cascade leading to tissue destruction in bacterial meningitis . The molecular mechanisms responsible for oxidant-induced neuronal injury in meningitis are explored in some depth . Genetic targeting and/or pharmacologic blockade of the implicated pathways may be a future strategy for therapeutic adjunctive measures to improve outcome and may hold substantial promise, in concert with antimicrobial agents, in humans with acute bacterial meningitis.

Int J Food Microbiol, 2003 Feb 15, 80(3), 211 - 5
Interaction of an odorant lactone with model phospholipid bilayers and its strong fluidizing action in yeast membrane; Aguedo M et al.; Some odorant lactones are naturally present in fruits or in fermented products; they can also be used as food additives and can be produced by microorganisms at the industrial scale by biotechnological processes . Gamma-decalactone was previously shown to have antimicrobial properties . We determined by infrared spectroscopy measurements that this compound rapidly diffused into model phospholipid bilayers (within 2 min), modifying the general physical state of a dimyristoyl-L-alpha-phosphatidylcholine (DMPC) film . In vivo, the lactone strongly increased membrane fluidity in the model yeast Yarrowia lipolytica, as evaluated by fluorescence anisotropy measurements . This effect was more important than that of benzyl alcohol, which is known as a fluidizing agent in living cells, and may explain the toxic action of gamma-decalactone in microorganisms .

Biochem J, 2003 Feb 15, 370(Pt 1), 233 - 43
Interactions of the designed antimicrobial peptide MB21 and truncated dermaseptin S3 with lipid bilayers: molecular-dynamics simulations; Shepherd CM et al.; Molecular-dynamics simulations covering 30 ns of both a natural and a synthetic antimicrobial peptide in the presence of a zwitterionic lipid bilayer were performed . In both simulations, copies of the peptides were placed in an alpha-helical conformation on either side of the bilayer about 10 A (1 A=0.1 nm) from the interface, with either the hydrophobic or the positively charged face of the helix directed toward the bilayer surface . The degree of peptide-lipid interaction was dependent on the starting configuration: surface binding and subsequent penetration of the bilayer was observed for the hydrophobically oriented peptides, while the charge-oriented peptides demonstrated at most partial surface binding . Aromatic residues near the N-termini of the peptides appear to play an important role in driving peptide-lipid interactions . A correlation between the extent of peptide-lipid interactions and helical stability was observed in the simulations . Insertion of the peptides into the bilayer caused a dramatic increase in the lateral area per lipid and decrease in the bilayer thickness, resulting in substantial disordering of the lipid chains . Results from the simulations are consistent with early stages of proposed mechanisms for the lytic activity of antimicrobial peptides . In addition to these 'free' simulations, 25 ns simulations were carried out with the peptides constrained at three different distances relative to the bilayer interface . The constraint forces are in agreement with the extent of peptide-bilayer insertion observed in the free simulations.

Org Lett, 2002 Nov 14, 4(23), 4089 - 92
Caminoside A, an antimicrobial glycolipid isolated from the marine sponge Caminus sphaeroconia; Linington RG et al.; Extracts of the marine sponge Caminus sphaeroconia showed potent activity in a screen for bacterial type III secretion inhibitors . Bioassay guided fractionation of the extract led to the isolation of the novel antimicrobial glycolipid caminoside A (1) . The structure of caminoside A was elucidated by analysis of spectroscopic data and chemical degradation.{structure: see text}

Wien Klin Wochenschr, 2002 Jul 31, 114(13-14), 616 - 9
Development of erythema migrans in spite of treatment with antibiotics after a tick bite; Maraspin V et al.; OBJECTIVES: The recent information on the appearance of erythema migrans despite prophylaxis with 200 mg of doxycycline was the stimulus for a search among our patients for those who developed the skin lesion regardless of receiving antibiotics after a tick bite . METHODS: Data were reviewed for adult patients with erythema migrans diagnosed at our institution from 1994 to July 2001, targeting those who received antibiotics after a tick bite . RESULTS: Seven of 5056 (0.14%) patients, diagnosed with typical erythema migrans, developed the skin lesion despite receiving antibiotics after a tick bite . Antibiotics were prescribed by general physicians: in four cases as prophylaxis of Lyme borreliosis within one day after tick detachment and in three cases because of development of acute respiratory tract infection two, five, and eight days after the bite, respectively . The dosages were as follows: azithromycin in a total dose of 3 g in three patients and 1.5 g in the fourth patient, amoxicillin-clavulanic acid 625 mg t.i.d . for ten days in the fifth patient, amoxycillin 500 mg t.i.d . for seven days followed by azithromycin 250 mg o.d . for eight days in the sixth, and amoxycillin 500 mg t.i.d . for eight days in the seventh . The patients (five females and two males, aged 18-61 years) were referred to our Department on average six (1-19) days after the appearance of skin lesions . They had typical solitary (five patients) or multiple (two patients) erythema migrans with the characteristics usually seen in European patients, except for a rather long incubation period (median value 28 days, range 10-40 days) . All laboratory tests, including the examination of cerebrospinal fluid in three patients with the disseminated form of the illness, were within normal range . Borrelial antibodies were demonstrated in only one patient . A skin biopsy specimen obtained from the site of the erythema migrans was culture positive for Borrelia in 2/4 patients . CONCLUSIONS: Our study did not enable us to assess the frequency of antimicrobial prophylaxis failure or the efficacy of individual antibiotics for the prevention of Lyme borreliosis . However, the seven patients presented demonstrate that antibiotic prophylaxis for Lyme borreliosis after a tick bite, at least in Europe, is not entirely effective.

Wien Klin Wochenschr, 2002 Jul 31, 114(13-14), 613 - 5
Duration of treatment for Lyme borreliosis: time for a critical reappraisal; Wormser GP et al.; Over time the recommended duration of antibiotic therapy for patients with erythema migrans has increased . This change in prescribing practice is not evidence-based . The presumptions that post-treatment subjective complaints, which occur in a minority of patients, may be reduced by increasing the duration of initial therapy or ameliorated by a repeat course of parenteral or oral antimicrobials, have not been supported by recent clinical trials . Recommendations on duration of treatment of early Lyme borreliosis deserve critical reappraisal.

J Chemother, 2002 Aug, 14(4), 373 - 7
Surgical antibiotic prophylaxis in a Turkish university hospital; Yalcin AN et al.; A prospective study was performed to assess the practice of antibiotic prophylaxis for surgical procedures in Pamukkale University Hospital, Denizli, Turkey . All surgical procedures performed between April 1 and July 31, 2001, were included . During the study period 897 operations were reviewed . 96% of all procedures were elective, 4% emergencies . Approximately 70.7% were clean surgery, 25.3% clean-contaminated, 2.8% contaminated, and 1.2% dirty . 98% of patients (879) received antibiotic prophylaxis . Although timing of prophylaxis was appropriate in all procedures, the duration of prophylaxis was optimal in only 47.7% of all cases . Sulbactam/ampicillin (SAM), cefazolin and cefepime were the most commonly used antibiotics during the study period . The results of our study suggest that the choice of prophylactic antimicrobial agent was inappropriate in most cases . In conclusion, we think that compliance regarding the optimal choice, frequency, and duration of perioperative antibiotic prophylaxis is not adequate in our hospital, and that more education on the subject is necessary.

J Chemother, 2002 Aug, 14(4), 366 - 72
Amoxicillin/clavulanic acid versus cefotaxime for antimicrobial prophylaxis in abdominal surgery: a randomized trial; Tonelli F et al.; Amoxicillin/clavulanic acid (amoxicillin 2 g/clavulanic acid 200 mg) has been administered in comparison to cefotaxime (2 g) for antimicrobial prophylaxis in 476 evaluable patients undergoing abdominal surgery at high risk of septic complications . Both antibiotics were administered as a single infusion . 205 evaluable patients (110 in amoxicillin/clavulanic acid group and 95 in cefotaxime group) underwent upper gastrointestinal surgery (including gastroduodenal and biliary surgery) . The wound infection rate was 4.5% for amoxicillin/clavulanic acid and 7.4% for cefotaxime, with no significant differences . Intra-abdominal abscesses were observed in 3 patients in the amoxicillin/clavulanic acid group and in 1 patient in the cefotaxime group . 271 evaluable patients (135 in amoxicillin/clavulanic acid group and 136 in cefotaxime group) underwent lower gastrointestinal surgery (including colorectal surgery).The wound infection rate was 11% for amoxicillin/clavulanic acid and 13% for cefotaxime, with no significant differences . A purulent discharge was present in 3 patients in both groups . Intra-abdominal abscesses were observed in 3 patients in the amoxicillin/clavulanic acid group and in 4 patients in the cefotaxime group . No serious adverse events and no cases of diarrhea were observed . In conclusion, in our experience amoxicillin/clavulanic acid proved to be as effective as cefotaxime in protecting patients from surgical infections in abdominal surgery . Its use in surgical prophylaxis may help decrease the cost of treatment and reduce the risk of resistance to antibiotics and superinfections.

J Chemother, 2002 Aug, 14(4), 332 - 5
Antibiotic use in an Italian university hospital; Mazzeo F et al.; The aim of this retrospective observational study was to investigate: a) expenditure for antibiotics with respect to the total pharmacy drug budget and to costs of other medical devices; b) the most frequently used antimicrobial classes and molecules; c) the clinical units that most frequently use antimicrobial therapy; d) the preferred route of administration; e) consumption patterns of antibiotics over two periods (January-September 1999 and January-September 2000) . The consumption of a single antimicrobial agent was expressed as daily defined doses (DDD) per 100 bed days . In 1999 drugs accounted for 56% of the total costs but decreased to 46% in 2000 . Antibiotics accounted for 15% of the pharmacy's overall acquisition costs in 1999 and dropped to 13% in 2000 . In both 1999 and 2000, penicillins were used most, followed by cephalosporins and aminoglycosides . In 1999, the most frequently used antibiotic was amoxicillin (4.02 DDD per 100 bed days) followed by ceftazidime, ampicillin, ceftriaxone, and co-amoxiclav . In 2000 ceftriaxone was the most commonly used antibiotic (4.35 DDD per 100 bed days) followed by co-amoxiclav, amoxicillin, ceftazidime . The general surgery, medical therapy and infectious diseases units accounted for the majority of penicillin consumption, while cephalosporins were most widely used in general surgery, orthopedics and neurosurgery units . Parenteral administration was the most widely used route in both years.

J Am Vet Med Assoc, 2002 Jul 1, 221(1), 103 - 8
Use of antimicrobial susceptibility testing of bacterial pathogens isolated from the milk of dairy cows with clinical mastitis to predict response to treatment with cephapirin and oxytetracycline; Constable PD et al.; OBJECTIVE: To determine whether results of antimicrobial susceptibility testing of bacterial pathogens isolated from the milk of dairy cows with clinical mastitis were associated with duration of clinical signs or bacteriologic cure rate following treatment with cephapirin and oxytetracycline . DESIGN: Observational study on a convenience sample . ANIMALS: 58 dairy cows with 121 episodes of clinical mastitis . PROCEDURE: Cows that only had abnormal glandular secretions were treated with cephapirin alone . Cows with an inflamed gland and abnormal glandular secretions were treated with oxytetracycline and cephapirin . Cows with systemic signs of illness, an inflamed gland, and abnormal glandular secretions were treated with oxytetracycline and flunixin meglumine and frequent stripping of the affected glands . The Kirby-Bauer method was used for antimicrobial susceptibility testing, and current guidelines were used to categorize causative bacteria as susceptible or resistant to the treatment regimen . RESULTS: Median durations of episodes of clinical mastitis caused by susceptible (n = 97) and resistant (24) bacteria were not significantly different . Bacteriologic cure rates at 14 and 28 days were similar for episodes caused by susceptible and resistant bacteria; however, for 56 episodes of clinical mastitis caused by gram-positive bacteria and treated with cephapirin alone, bacteriologic cure rate at 28 days was significantly higher for susceptible than for resistant bacteria . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that antimicrobial susceptibility testing was of no value in predicting duration of clinical signs or bacteriologic cure rate in dairy cows with mastitis, except for episodes caused by gram-positive organisms treated with intramammary administration of cephapirin alone.

Free Radic Biol Med, 2002 Nov 15, 33(10), 1306 - 13
Iron and the redox status of the lungs; Quinlan GJ et al.; Iron is an element essential for the survival of most aerobic organisms . However, when its availability is not adequately controlled, iron, can catalyze the formation of a range of aggressive and damaging reactive oxygen species, and act as a microbial growth promoter . Depending on the concentrations formed such species can cause molecular damage or influence redox signaling mechanisms . This review describes recent knowledge concerning iron metabolism in the lung, during both health and disease . In the lower part of the lung a small redox active pool of iron is required for reasons that are at present unclear, but may be related to antimicrobial functions . When the concentration of iron is increased in the lung (usually because of environmental exposure), iron is deleterious and contributes to a range of chronic and acute respiratory diseases . Moreover, aberrant regulation of iron metabolism, and/or deficient antioxidant protection, is also associated with acute lung diseases, such as the acute respiratory distress syndrome (ARDS) . Iron, with the consequent production of reactive oxygen species (ROS), microbial growth promotion, and adverse signaling is strongly implicated as a major contributor to the pathogenesis of numerous disease processes involving the lung . Heme oxgenase, an enzyme that produces reactive iron from heme catabolism, is also briefly discussed in relation to lung disease.

J Am Vet Med Assoc, 2002 Nov 1, 221(9), 1306 - 10
Postoperative infection with Actinobacillus spp in horses: 10 cases (1995-2000); Smith MA et al.; OBJECTIVE: To determine features of postoperative wound infection caused by Actinobacillus spp in horses undergoing clean, elective surgery and to evaluate bacterial susceptibility profiles of bacteria isolated . DESIGN: Retrospective study . ANIMALS: 10 horses . PROCEDURE: Data were retrieved from medical records and the microbiology laboratory database . RESULTS: 1,604 horses underwent clean, elective surgical procedures during the study period . Of these, 23 (1.43%) had postoperative wound infections, and Actinobacillus spp was isolated from 10 of these 23 (43%) . Surgical procedures in these 10 horses included laryngoplasty with ventriculocordectomy (n = 3), arthroscopy (3), desmotomy of the accessory ligament of the superficial digital flexor tendon (2), removal of laryngoplasty prostheses (1), and hygroma resection (1) . Seven horses survived, and 3 were euthanatized . All 10 Actinobacillus isolates were resistant to penicillin, and 6 were resistant to trimethoprim-sulfamethoxazole . All isolates were susceptible to ceftiofur and gentamicin . During the 5-year period of the study, Actinobacillus organisms were isolated from 35 of 513 (6.8%) samples from the general hospital population submitted for bacterial culture and antimicrobial susceptibility testing . CONCLUSIONS AND CLINICAL RELEVANCE: During the study period, Actinobacillus spp was isolated from a higher than expected percentage of horses that developed postoperative wound infections after clean, elective surgery . Susceptibility profiles for these isolates were different from typical susceptibility profiles for Actinobacillus isolates, suggesting that a pattern of resistance may be emerging.

Crit Care Clin, 2002 Oct, 18(4), 729 - 48
Rheumatologic diseases in the intensive care unit: epidemiology, clinical approach, management, and outcome; Janssen NM et al.; Patients with systemic rheumatic diseases may be admitted to the ICU because of worsening of or development of a new manifestation of the rheumatic disease, infections caused by immunosuppression, or adverse effects of drugs used to treat rheumatic diseases . Sometimes an unrelated, acute disorder may become life threatening because of the underlying rheumatic disorder . Rheumatoid arthritis is the most common rheumatic disease seen in ICU patients, followed by systemic lupus erythematosus and scleroderma . These three conditions together account for up to 75% of rheumatic cases admitted to the ICU . The respiratory system is the organ system most commonly affected in the acute process, followed by the renal, gastrointestinal, and nervous systems . More than 50% of admissions result from infections, and 25% to 35% result from exacerbation of the underlying rheumatic condition . In about 20% of patients, the rheumatic disorder may be diagnosed for the first time in the ICU . An aggressive approach should be pursued to establish the diagnosis of either disease exacerbation or infection . Delay in instituting appropriate immunosuppressive or antimicrobial therapy may result in multiple organ system failure and a poor outcome . The mortality rate in patients with rheumatic disease exceeds that predicted by the APACHE II or SAPS II scores and is higher than that in nonrheumatologic ICU admissions . The mortality may exceed 50% in patients admitted for infection; the prognosis is comparatively better for patients with exacerbations of disease activity . Renal failure, coma, and acute abdomen are predictors of poor outcome . Early recognition of abdominal complications requiring surgical intervention may help reduce mortality.

Arch Pediatr Adolesc Med, 2002 Nov, 156(11), 1114 - 9
Antibiotic prescribing by primary care physicians for children with upper respiratory tract infections; Nash DR et al.; OBJECTIVES: To determine if the rate of appropriate antibiotic use in the treatment of children with bronchitis, viral upper respiratory tract infections, sinusitis, otitis media, and pharyngitis has changed in recent years and to identify factors that are associated with the use of inappropriate antibiotic therapy . DESIGN: The National Ambulatory Medical Care Survey was used to examine the antimicrobial prescribing habits of physicians who provide primary care for children . Data were analyzed from 1995-1998 . SETTING: Office-based physician practices . PARTICIPANTS: Pediatricians, family physicians, and generalists completing survey forms for patients younger than 18 years . MAIN OUTCOME MEASURE: The appropriate use of antibiotics for upper respiratory tract infections . RESULTS: Multivariate analyses were used to examine factors associated with the use of inappropriate antibiotics to treat either upper respiratory tract infections or bronchitis . Patients seen in 1998 and diagnosed as having upper respiratory tract infections were 0.69 (95% confidence interval, 0.59-0.81) times less likely to be treated with antibiotics compared with patients seen in 1995 . Multivariate analyses were also used to assess factors associated with the use of antibiotics with a suboptimal therapeutic profile for the treatment of either sinusitis or otitis media . Children diagnosed as having either sinusitis or otitis media were 0.3 (95% confidence interval {CI}, 0.16-0.48) times less likely to receive antibiotics with a suboptimal therapeutic effect in 1998 compared with 1995 . CONCLUSIONS: Physicians are slowly improving their antibiotic prescribing patterns but the use of inappropriate antibiotics is still common . Almost half of patients with upper respiratory tract infections receive antibiotics.

Proc Natl Acad Sci U S A, 2002 Nov 12, 99(23), 14658 - 63 Epub 2002 Nov 04.
Resistance to the macrolide antibiotic tylosin is conferred by single methylations at 23S rRNA nucleotides G748 and A2058 acting in synergy; Liu M et al.; The macrolide antibiotic tylosin has been used extensively in veterinary medicine and exerts potent antimicrobial activity against Gram-positive bacteria . Tylosin-synthesizing strains of the Gram-positive bacterium Streptomyces fradiae protect themselves from their own product by differential expression of four resistance determinants, tlrA, tlrB, tlrC, and tlrD . The tlrB and tlrD genes encode methyltransferases that add single methyl groups at 23S rRNA nucleotides G748 and A2058, respectively . Here we show that methylation by neither TlrB nor TlrD is sufficient on its own to give tylosin resistance, and resistance is conferred by the G748 and A2058 methylations acting together in synergy . This synergistic mechanism of resistance is specific for the macrolides tylosin and mycinamycin that possess sugars extending from the 5- and 14-positions of the macrolactone ring and is not observed for macrolides, such as carbomycin, spiramycin, and erythromycin, that have different constellations of sugars . The manner in which the G748 and A2058 methylations coincide with the glycosylation patterns of tylosin and mycinamycin reflects unambiguously how these macrolides fit into their binding site within the bacterial 50S ribosomal subunit.

J Biol Chem, 2003 Jan 10, 278(2), 1310 - 5 Epub 2002 Nov 01.
Translocation of analogues of the antimicrobial peptides magainin and buforin across human cell membranes; Takeshima K et al.; Cationic antimicrobial peptides play important roles in innate immunity . Compared with extensive studies on peptide-bacteria interactions, little is known about peptide-human cell interactions . Using human cervical carcinoma HeLa and fibroblastic TM12 cells, we investigated the cellular uptake of fluorescent analogues of the two representative antimicrobial peptides magainin 2 and buforin 2 in comparison with the representative Arg-rich cell-penetrating Tat-(47-57) peptide (YGRKKRRQRRR) . The dose, time, temperature, and energy dependence of translocation suggested that the three peptides cross cell membranes through different mechanisms . The magainin peptide was internalized within a time scale of tens of minutes . The cooperative concentration dependence of uptake suggested that the peptide forms a pore as an intermediate similar to the observations in model membranes . Furthermore, the translocation was coupled with cytotoxicity, which was larger for tumor HeLa cells . In contrast, the buforin peptide translocated within 10 min by a temperature-independent, less concentration-dependent passive mechanism without showing any significant cytotoxicity at the highest concentration investigated (100 microm) . The uptake of the Tat peptide was proportional to the peptide concentration, and the concentration dependence was lost upon ATP depletion . The peptide exhibited a moderate cytotoxicity at higher concentrations . The time course did not show saturation even after 120 min . The buforin peptide, covalently attached to the 28-kDa green fluorescent protein, also entered cells, suggesting a potency of the peptide as a vector for macromolecular delivery into cells . However, the mechanism appeared to be different from that of the parent peptide.

Med Device Technol, 2002 Oct, 13(8), 10 - 4, 16
New biointeracting materials; Sandhu S et al.; This article reports on advances in haemocompatible and antimicrobial coatings . A polymer is described that has nonthrombogenic and antithrombogenic properties on the same polymer backbone, which prevents protein adsorption and inhibits thrombin at the same time . A separate polymer formulation has also been developed that is reportedly biocompatible, lubricious and antimicrobial.

Minn Med, 2002 Oct, 85(10), 38 - 43
Community and environmental health effects of concentrated animal feeding operations; Kirkhorn SR; High-density concentrated animal feeding operations (CAFOs) have become an increasing source of concern with respect to their impact on health, the environment, and quality of life in the communities in which they are located . A growing body of literature has identified a number of potential adverse effects, including the development of antimicrobial resistance patterns, groundwater contamination, and occupational respiratory disease . The odor associated with CAFOs has had a detrimental effect on the quality of life of rural residents, and there may also be associated adverse health effects . Physicians in rural areas may be asked to assess patients with concerns related to neighboring CAFOs and may be drawn into a political battle regarding the authorization of the development of additional CAFOs . This article reviews current research on the community, environmental, and occupational health effects associated with high-density animal production facilities . It also discusses recommendations for evaluating patients affected by CAFO odors and steps to decrease occupational and community exposure.

Pediatr Surg Int, 2002 Sep, 18(5-6), 556 - 8 Epub 2002 Jul 11.
Computed tomography-guided percutaneous drainage of intra-abdominal abscesses in neutropenic children; Jaing TH et al.; The mortality associated with undrained intra-abdominal abscesses is high . Computed tomography-guided percutaneous drainage (CT-PD), a minimally invasive technique, allows a drainage catheter to be inserted into fluid collections throughout the body with minimal risk . We described two neutropenic patients with intra-abdominal abscesses treated with CT-PD after they failed to respond to antimicrobial therapy . With this modality, the surgery was successfully avoided or delayed . We are of an opinion that CT-PD is an efficient and simple urgent radiology procedure.

Nat Rev Drug Discov, 2002 Nov, 1(11), 895 - 910
The future challenges facing the development of new antimicrobial drugs; Coates A et al.; The emergence of resistance to antibacterial agents is a pressing concern for human health . New drugs to combat this problem are therefore in great demand, but as past experience indicates, the time for resistance to new drugs to develop is often short . Conventionally, antibacterial drugs have been developed on the basis of their ability to inhibit bacterial multiplication, and this remains at the core of most approaches to discover new antibacterial drugs . Here, we focus primarily on an alternative novel strategy for antibacterial drug development that could potentially alleviate the current situation of drug resistance--targeting non-multiplying latent bacteria, which prolong the duration of antimicrobial chemotherapy and so might increase the rate of development of resistance.

J Virol, 2002 Dec, 76(23), 11911 - 9
Neonates mount robust and protective adult-like CD8(+)-T-cell responses to DNA vaccines; Zhang J et al.; Neonates are thought to mount less vigorous adaptive immune responses than adults to antigens and infectious agents . This concept has led to a delay in the administration of many currently available vaccines until late infancy or early childhood . It has recently been shown that vaccines composed of plasmid DNA can induce both humoral and cell-mediated antimicrobial immunity when administered within hours of birth . In most of these studies, immune responses were measured weeks or months after the initial vaccination, and it is therefore questionable whether the observed responses were actually the result of priming of splenocytes within the neonatal period . Here we show that DNA vaccination at birth results in the rapid induction of antigen-specific CD8(+) T cells within neonatal life . Analyses of T-cell effector functions critical for the resolution of many viral infections revealed that neonatal and adult CD8(+) T cells produce similar arrays of cytokines . Furthermore, the avidities of neonatal and adult CD8(+) T cells for peptide and the rapidity with which they upregulate cytokine production after recall encounters with antigen are similar . Protective immunity against the arenavirus lymphocytic choriomeningitis virus, which is mediated by CD8(+) cytotoxic T cells, is also rapidly acquired within the neonatal period . Collectively these data imply that, at least in the case of CD8(+) T cells, neonates are not as immunodeficient as previously supposed and that DNA vaccines may be an effective and safe means of providing critical cell-mediated antiviral immunity extremely early in life.

Biophys J, 2002 Nov, 83(5), 2393 - 407
Analysis and evaluation of channel models: simulations of alamethicin; Tieleman DP et al.; Alamethicin is an antimicrobial peptide that forms stable channels with well-defined conductance levels . We have used extended molecular dynamics simulations of alamethicin bundles consisting of 4, 5, 6, 7, and 8 helices in a palmitoyl-oleolyl-phosphatidylcholine bilayer to evaluate and analyze channel models and to link the models to the experimentally measured conductance levels . Our results suggest that four helices do not form a stable water-filled channel and might not even form a stable intermediate . The lowest measurable conductance level is likely to correspond to the pentamer . At higher aggregation numbers the bundles become less symmetrical . Water properties inside the different-sized bundles are similar . The hexamer is the most stable model with a stability comparable with simulations based on crystal structures . The simulation was extended from 4 to 20 ns or several times the mean passage time of an ion . Essential dynamics analyses were used to test the hypothesis that correlated motions of the helical bundles account for high-frequency noise observed in open channel measurements . In a 20-ns simulation of a hexameric alamethicin bundle, the main motions are those of individual helices, not of the bundle as a whole . A detailed comparison of simulations using different methods to treat long-range electrostatic interactions (a twin range cutoff, Particle Mesh Ewald, and a twin range cutoff combined with a reaction field correction) shows that water orientation inside the alamethicin channels is sensitive to the algorithms used . In all cases, water ordering due to the protein structure is strong, although the exact profile changes somewhat . Adding an extra 4-nm layer of water only changes the water ordering slightly in the case of particle mesh Ewald, suggesting that periodicity artifacts for this system are not serious.

Ophthalmology, 2002 Nov, 109(11), 2118 - 22
Conservative management of necrotizing fasciitis of the eyelids; Luksich JA et al.; OBJECTIVE: To describe the management of patients with necrotizing fasciitis of the eyelids . DESIGN: Retrospective, noncomparative interventional case series . PARTICIPANTS: Seven patients with necrotizing fasciitis limited to the eyelids . METHODS: Retrospective review of the charts and photographs of seven patients with necrotizing fasciitis limited to the eyelids . MAIN OUTCOME MEASURES: Eyelid function and appearance, mortality, and morbidity . RESULTS: Seven of seven patients had good eyelid function and adequate appearance without reconstruction after healing . No deaths occurred . CONCLUSIONS: Eyelid necrosis due to necrotizing fasciitis can be a devastating condition . The morbidity and mortality of selected cases are reduced with prompt and appropriate antimicrobial therapy and nonaggressive debridement of necrotic tissue after autodemarcation of the necrotic zone.

Haematologica, 2002 Nov, 87(11), 1192 - 9
Feasibility of a mixed inpatient-outpatient model of peripheral blood stem cell transplantation for multiple myeloma; Morabito F et al.; BACKGROUND AND OBJECTIVES: A progressively growing number of peripheral blood stem cell transplants (PBSCTs) are being performed in patients with newly diagnosed multiple myeloma (MM) since they are ever more frequently being offered as up-front therapy . Furthermore, there are considerable concerns regarding the appropriate use of health care resources in order to reduce costs associated with PBSCT . One of the strategies attempted to reach this goal is outpatient-based PBSCT . DESIGN AND METHODS: The aim of this study was to analyze the feasibility of a mixed inpatient-outpatient model (MIOM) for MM patients receiving high-dose melphalan, and homogeneously undergoing autologous PBSCT, antimicrobial and antiviral prophylaxis and post-transplant growth factor treatment . Furthermore, we retrospectively compared results of the MIOM with those of the traditional total inpatient model (TIM) . RESULTS: MIOM was applied for 60 transplants in a total of 29 MM patients . Results were compared with retrospective data concerning the traditional TIM for 40 transplants (27 MM patients) . MIOM cases were older than TIM ones (55.3 6.3 years vs 49.6 9.2 years, p=0.01), but were comparable for sex and disease status . Granulocyte recovery time was shorter in the MIOM group (9.0 0.7 vs 9.7 1.2 days, p=0.004), while a similar number of stem cells were infused . There was no difference in platelet engraftment . The number of episodes and duration of grade II-IV mucositis were similar in both groups . Fever occurred in fewer MIOM cases (25% v 51.6%, p=0.02), while its duration was similar . In multivariate analysis, mucositis (grades II-IV) was the sole independent predictor of fever development (p=0.002) . Half of the MIOM cases never required re-admission, 26 were re-admitted (median hospital stay 9 days) and 4 cases were not discharged (median hospital stay 15 days) . The median time to discharge of TIM cases was 20 days . Non-hematologic toxicities were low in both groups . INTERPRETATION AND CONCLUSIONS: Since outpatient management and liberal hospitalization criteria have resulted in safe conduct of MIOM transplants, this program can be safely offered to MM patients.

Vet Microbiol, 2002 Dec 20, 90(1-4), 383 - 94
The innate immune response against Brucella in humans; Dornand J et al.; Pathogens have developed different strategies to survive and multiply within their host . Among them is the ability to control phagocyte apoptosis while another is to affect the expression of cytokines which is necessary for a normal protective function of the immune response . To establish themselves and cause chronic disease in humans and animals, Brucella spp . invade and proliferate within monocytic phagocytes . We have established that in humans, Brucella suis impairs the apoptosis of monocytes and macrophages, thus preventing its host cell elimination . In mice, which are not naturally colonized by the bacteria, Brucella infection results in Type1 (Th1) cellular immune response which promotes a clearance of the bacterial organism . The development of this response is under the control of major cytokines like TNF-alpha, IFN-gamma and IL-12 produced at the onset of infection . We have observed that in humans, B . suis-infected macrophages which produce IL-1, IL-6, IL-10 and several chemokines including IL-8, do not secrete TNF-alpha . By constructing null mutants, we demonstrated that this inhibition involves the outer membrane protein Omp25 of Brucella, however the mechanism regulating the inhibition has not yet been clearly defined . It is likely that the Omp25-induced effect on TNF-alpha production assists bacterial evasion of antimicrobial defences at different levels . Firstly, by preventing the autocrine activation of macrophages thus inhibiting innate immunity and secondly by impairing the production of IL-12 and the development of a Th1 type specific immunity . In addition to the central role of the macrophage in Brucella infection, others cells of the innate immune response are recruited and influenced by the interactions between bacteria and host . For instance, human Vgamma9Vdelta2 T-cells play an important role in the early response to infection with intracellular pathogens . Evidence has been presented that their number dramatically increased in the peripheral blood of patients with acute brucellosis . We have shown that human Vgamma9Vdelta2 T-cells can be specifically activated by non-peptidic low molecular weight compound(s) from B . suis lysate or by soluble factors produced by B . suis-infected macrophages . Under these conditions, they produce TNF-alpha and IFN-gamma and reduce the bacterial multiplication inside infected autologous macrophages . This impairment of B . suis multiplication is due to both soluble factors released from activated gammadeltaT-cells (including TNF-alpha and IFN-gamma) and to a contact-dependent cytotoxicity directed against the infected cells . The interactions between the bacteria and these cells can counteract the intramacrophagic development of the bacteria and finally influence the further development of the host defense . We hypothesize that the chronicity or the elimination of the infection will depend on the balance between contradictory effects induced by the bacteria which favor either the host or the pathogen . Moreover, the interrelationship between the different cells must be taken into account in the analysis of the virulence of the bacteria and in the development of in vitro models of human macrophage infection .

Aquat Toxicol, 2003 Jan 10, 62(1), 27 - 33
Inhibition of cytochrome p450 enzymes by enrofloxacin in the sea bass (Dicentrarchus labrax); Vaccaro E et al.; Currently, there are no reports on the effects of enrofloxacin (EF), a fluoroquinolone antibiotic, on the cytochrome p450 enzymes in fish, although its use as antimicrobial agent in aquaculture has been put forward . Therefore, the in vivo and in vitro effects of EF on hepatic p450 enzymes of sea bass, a widespread food-producing fish, have been evaluated . Sea bass pretreated with a single dose of EF (3 mg/kg i.p.) or with three daily doses of EF (1 mg/kg i.p.) markedly depressed the microsomal N-demethylation of aminopyrine, erythromycin, the O-deethylation of 7-ethoxycoumarin, ethoxyresorufin and the 6beta-testosterone hydroxylase . In vitro experiments showed that EF at 10 microM inhibited the above-mentioned activities and, in particular, the erythromycin N-demethylase (ERND) and 6beta-testosterone-hydroxylase, likely dependant on a p450 3A isoform . When the nature of ERND inhibition by EF was specifically studied with sea bass liver microsomes, it was found that EF is a potent mechanism-based inhibitor, with K(i) of 3.7 microM and a K(inact) of 0.045 min(-1) . An immunoblot analysis with anti p450 3A27 of trout showed that the p450 3A isoform, constitutively expressed in sea bass, is particularly susceptible to inactivation by EF . In vitro experiments with sea bass microsomes have also demonstrated that EF is oxidative deethylated by the p450 system to ciprofloxacin (CF) and that this compound maintains the ability to inactivate the p450 enzymes . The mechanism by which EF or CF inactivate the p450 enzymes has not been studied but an attack of p450 on the cyclopropan ring, present, both in EF and CF structure, with the formation of electrophilic intermediates (i.e . radicals) has been postulated . In conclusion, the EF seems to be a powerful inhibitor of p450s in the sea bass . Therefore, the clinical use of this antibiotic in aquaculture has to be considered with caution.

J Ethnopharmacol, 2002 Nov, 83(1-2), 129 - 34
Antimicrobial activity of some plants used for the treatment of livestock disease in the Eastern Cape, South Africa; Masika PJ et al.; Approximately 75% of rural livestock owners in the Eastern Cape province of South Africa use plants or plant based remedies to treat their livestock . Prominent among these plants are Combretum caffrum, Salix capensis and Schotia latifolia . Water, methanolic and acetonic extracts as well as decoctions of the three plants were screened against ten bacteria and five fungi . The results of the antibacterial assay indicated significant activity against all the Gram-positive bacteria tested with the minimum inhibitory concentrations ranging from 0.1 to 5.0 mg/ml . A few of the extracts showed minimal activity, but the majority of extracts were not active on the Gram-negative bacteria . Generally, all the extracts showed some antifungal activity against the five test fungi . Methanolic extracts exhibited higher fungal growth inhibition, whereas the water extracts showed the least inhibition . It was noteworthy that some water extracts promoted fungal growth.

Mol Immunol, 2002 Nov, 39(7-8), 383 - 94
Structural biology of the C1 complex of complement unveils the mechanisms of its activation and proteolytic activity; Arlaud GJ et al.; C1 is the multimolecular protease that triggers activation of the classical pathway of complement, a major element of antimicrobial host defense also involved in immune tolerance and various pathologies . This 790,000 Da complex is formed from the association of a recognition protein, C1q, and a catalytic subunit, the Ca2+-dependent tetramer C1s-C1r-C1r-C1s comprising two copies of each of the modular proteases C1r and C1s . Early studies mainly based on biochemical analysis and electron microscopy of C1 and its isolated components have allowed for characterization of their domain structure and led to a low-resolution model of the C1 complex in which the elongated C1s-C1r-C1r-C1s tetramer folds into a more compact, "8-shaped" conformation upon interaction with C1q . A major strategy used over the past years has been to dissect the C1 proteins into modular segments to characterize their function and solve their structure by either X-ray crystallography or nuclear magnetic resonance spectroscopy (NMR) . The purpose of this review is to focus on this information, with particular emphasis on the architecture of the C1 complex and the mechanisms underlying its activation and proteolytic activity.

J Clin Pharmacol, 2002 Nov, 42(11 Suppl), 71S - 81S
Respiratory and immunologic consequences of marijuana smoking; Tashkin DP et al.; Habitual smoking of marijuana has a number of effects on the respiratory and immune systems that may be clinically relevant . These include alterations in lung function ranging from no to mild airflow obstruction without evidence of diffusion impairment, an increased prevalence of acute and chronic bronchitis, striking endoscopic findings of airway injury (erythema, edema, and increased secretions) that correlate with histopathological alterations in bronchial biopsies, and dysregulated growth of the bronchial epithelium associated with altered expression of nuclear and cytoplasmic proteins involved in the pathogenesis of bronchogenic carcinoma . Other consequences of regular marijuana use include ultrastructual abnormalities in human alveolar macrophages along with impairment of their cytokine production, antimicrobial activity, and tumoricidal function . Cannabinoid receptor expression is altered in leukocytes collected from the blood of chronic smokers, and experimental models support a role for delta9-tetrahydrocannabinol in suppressing T cell function and cell-mediated immunity . The potential for marijuana smoking to predispose to the development of respiratory malignancy is suggested by several lines of evidence, including the presence of potent carcinogens in marijuana smoke and their resulting deposition in the lung, the occurrence of premalignant changes in bronchial biopsies obtained from smokers of marijuana in the absence of tobacco, impairment of antitumor immune defenses by delta9-tetrahydrocannabinol, and several clinical case series in which marijuana smokers were disproportionately over represented among young individuals who developed upper or lower respiratory tract cancer . Additional well designed epidemiological and immune monitoring studies are required to determine the potential causal relationship between marijuana use and the development of respiratory infection and/or cancer.

Anesthesiology, 2002 Nov, 97(5), 1162 - 7
Sulfite supported lipid peroxidation in propofol emulsions; Baker MT et al.; BACKGROUND: Sodium metabisulfite is added to a commercial propofol emulsion as an antimicrobial agent . The sulfite ion (SO3(-2)) is capable of undergoing a number of reactions, including autooxidation and the promotion of lipid peroxidation . This study evaluated sulfite reactivity in propofol emulsions by determining thiobarbituric acid reacting substances (TBARS), sulfite depletion, and emulsion pH in emulsions containing sulfite or EDTA . METHODS: Commercial EDTA and sulfite propofol emulsions were compared, and 10% soybean oil emulsion containing various additives were evaluated for TBARS, sulfite, and pH . TBARS were analyzed with a modified thiobarbituric acid method . Sulfite was analyzed by the reaction of sulfite with 5,5'-dithiobis(2-nitrobenzoic acid) . pH was measured by glass electrode methodology . RESULTS: Thiobarbituric acid reacting substances were detectable in commercial sulfite propofol emulsions in concentrations ranging from 0.02 to 0.22 microg/ml based on malondialdehyde . No TBARS were detected in EDTA propofol emulsions . Incubation (37 degrees C, up to 6 h) of sulfite propofol emulsions in air resulted in further increases in TBARS (35-160%) . No increases occurred in incubated EDTA propofol emulsions . Metabisulfite (0.25 mg/ml) alone added to 10% soybean oil resulted in large increases in TBARS that were inhibited in part by propofol (10 mg/ml) and completely by ascorbic acid (0.05 mg/ml) . Soybean oil emulsion pH declined rapidly on the addition of metabisulfite (0.25 mg/ml) . The addition of propofol (10 mg/ml) partially inhibited the decline in pH and ascorbic acid (0.05 mg/ml) completely inhibited it . CONCLUSION: These results show that sulfite supports the peroxidation of lipids in soybean oil emulsions and propofol functions to partially inhibit these processes.

Science, 2002 Nov 1, 298(5595), 1025 - 9
Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2; Biragyn A et al.; beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin . We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation . These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.

Altern Med Rev, 2002 Oct, 7(5), 410 - 7
The treatment of small intestinal bacterial overgrowth with enteric-coated peppermint oil: a case report; Logan AC et al.; Recent investigations have shown that bacterial overgrowth of the small intestine is associated with a number of functional somatic disorders, including irritable bowel syndrome (IBS), fibromyalgia, and chronic fatigue syndrome . A number of controlled studies have shown that enteric-coated peppermint oil (ECPO) is of benefit in the treatment of IBS . However, despite evidence of strong antimicrobial activity, ECPO has not been specifically investigated for an effect on small intestinal bacterial overgrowth (SIBO) . A case report of a patient with SIBO who showed marked subjective improvement in IBS-like symptoms and significant reductions in hydrogen production after treatment with ECPO is presented . While further investigation is necessary, the results in this case suggest one of the mechanisms by which ECPO improves IBS symptoms is antimicrobial activity in the small intestine.

Phytother Res, 2002 Nov, 16(7), 692 - 5
Antimicrobial potential of two different Hypericum species available in India; Mukherjee PK et al.; The antimicrobial activity of extracts of the leaves and stems of two different varieties of Hypericum was evaluated by the disc diffusion method . Petroleum ether, acetone, chloroform and methanol extracts of Hypericum mysorense and Hypericum patulum stems and leaves were investigated for their antimicrobial activity against six different strains of bacteria and fungi by the zone of inhibition method (ZIM) . The results showed that both the stem and leaf extracts of both species have a very broad spectrum of antibacterial activity . The petroleum ether and acetone extract of the leaves and stems of H . mysorense did not show antifungal effects against any of the six fungal organisms tested but other extracts showed a potential antifungal effect which was comparable to that of griseofulvin, the standard antifungal agent . Thus these results demonstrate that the leaf and stem extracts of both the Hypericum species have a very broad spectrum of activity and suggest that they may be useful in the treatment of various microbial infections .

Surg Laparosc Endosc Percutan Tech, 2002 Oct, 12(5), 347 - 52
The effect of the pneumoperitoneum on the peritoneal defense mechanisms in diabetic rats; Gozis G et al.; To investigate the effects of pneumoperitoneum on the peritoneal defense mechanism induced by streptozocin infusion during laparoscopic surgery in diabetic rats and to show the importance of regulation of diabetes for peritoneal defense mechanisms . One hundred twenty-six Sprague-Dawley male rats were allocated into six groups each consisting of 21 rats: group 1, nondiabetic sham laparotomy (control); group 2, nondiabetic pneumoperitoneum (control); group 3, uncontrolled diabetes plus sham laparotomy; group 4, controlled diabetes plus sham laparotomy; group 5, uncontrolled diabetes plus pneumoperitoneum; and group 6, controlled diabetes plus pneumoperitoneum . Diabetes was constituted by intraperitoneal infusion of one dose of 60 mg/kg streptozotocin, and diabetes was regulated (in groups 4 and 6) by subcutaneous injection of 10 IU/kg insulin in the morning and evening after the blood glucose measurements since the fourth day . Peritoneal fluid samples were taken at the zero, second, and sixth hours after sham laparotomy for groups 1, 3, and 4 and after pneumoperitoneum for groups 2, 5, and 6 on the seventh day . Total peritoneal cell count, antibacterial activity of the peritoneal fluid, and types of phagocytic cells in the peritoneal fluid were assessed . Peritoneal cell count was found to be lower in uncontrolled diabetes due to high blood glucose levels (>200 mg/dL), which led to slow migration of phagocytic cells into the peritoneum . Pneumoperitoneum had augmented the effect on phagocytic cell migration to the peritoneum compared with the sham laparotomy in controlled diabetic rats . Uncontrolled and controlled diabetes have adverse effects on peritoneal defense mechanism killing functions by interfering with the antimicrobial activity of peritoneal fluid.

J Clin Microbiol, 2002 Nov, 40(11), 4211 - 7
Optimal DNA isolation method for detection of bacteria in clinical specimens by broad-range PCR; Rantakokko-Jalava K et al.; Broad-range amplification of bacterial DNA from clinical specimens has proved useful for the diagnosis of various bacterial infections, especially during antimicrobial treatment of the patient . Optimal sample processing protocols for diagnostic broad-range bacterial PCR should release DNA from an array of target organisms with equal efficiencies and wash out inhibitory factors from various sample types without introducing bacterial DNA contamination to the amplification reaction . In the present study, two physical cell wall disintegration methods, bead beating and sonication, for enhanced detection of organisms with difficult-to-lyse cell walls were studied . The analytical sensitivities of several commercially available DNA purification kits, which were used with and without additional cell disintegration steps, were compared by using dilution series of model bacteria . Selected purification methods were used to process routine clinical specimens in parallel with the standard phenol-ether DNA extraction, and the results obtained by bacterial PCR and sequencing with the two template preparations were compared . The method with the DNA isolation kit with the lowest detection limits from the bacterial suspensions (Masterpure) did not prove to be superior to the standard method when the two methods were applied to 69 clinical specimens . For another set of 68 clinical specimens, DNA purified with a glass fiber filter column (High Pure) with an additional sonication step yielded results well in accord with those obtained by the standard method . Furthermore, bacterial DNA was detected in four samples that remained PCR negative by the standard method, and three of these contained DNA from gram-positive pathogens . Three samples were positive by the standard method only, indicating the limitations of applying any single method to all samples.

Lancet Infect Dis, 2002 Nov, 2(11), 667 - 76
Controlling infection by tuning in and turning down the volume of bacterial small-talk; Camara M et al.; As the prevalence of bacterial resistance to multiple antibiotics increases it is becoming progressively more difficult to treat infections and, in many cases, the available therapeutic options are severely limited . Hence, there is a growing urgency to the search for novel targets and the development of new antimicrobials . To infect a host and cause disease bacteria produce an array of virulence determinants that contribute to pathogenesis . It is now known that many different Gram-positive and Gram-negative pathogens communicate via the production and sensing of small, diffusible signal molecules, to coordinate virulence determinant production . As a consequence, this event, now termed quorum sensing, represents a novel therapeutic target offering the opportunity to attenuate virulence, and thus control infection, by blocking cell-to-cell communication.

Curr Treat Options Gastroenterol, 2002 Dec, 5(6), 443 - 449
Amebic Liver Abscess; Goessling W et al.; Amebic liver abscess should be suspected in travelers returning from endemic areas or in immunocompromised patients who present with fever, right upper quadrant pain, hepatomegaly, and a liver lesion on an imaging study . Rapid initiation of therapy without serologic confirmation of infection, if necessary, is important to minimize complications . Metronidazole is given orally or intravenously for 14 days . The drug is generally well tolerated and leads to resolution of symptoms in most patients within 2 to 3 days . It is effective against luminal cysts in only 50% of patients and, therefore, must be followed by a course of treatment with paromomycin (Humatin; Parke-Davis, Morris Plains, NJ) or another luminal antiamebic agent to eradicate the parasite . Image-guided drainage of an amebic liver abscess is indicated in patients who do not respond to antimicrobial therapy or who are at risk of abscess rupture . Surgery is reserved for patients with a ruptured abscess . Although medical therapy is generally successful in the treatment of infection caused by Entamoeba histolytica, the development of potent vaccines will be needed for worldwide eradication of disease attributable to E . histolytica.

Pathology, 2002 Oct, 34(5), 462 - 5
Susceptibility of Erysipelothrix rhusiopathiae to antimicrobial agents and home disinfectants; Fidalgo SG et al.; AIM: Erysipelothrix rhusiopathiae causes the occupationally-related infection erysipeloid in humans, and may be responsible for infections in lobster fishermen in Western Australia . There are little recent data pertaining to antimicrobial susceptibility, or susceptibility to disinfectants that might be used in the environment . The aim of this study was to determine the susceptibility of E . rhusiopathiae from human, animal and environmental sources to various antimicrobial agents and disinfectants . METHODS: The susceptibility of 60 E rhusiopathiae isolates was determined using a recommended agar dilution procedure . Susceptibility to disinfectants was achieved using a broth microdilution method . RESULTS: Penicillin and ceftriaxone, with low minimum inhibitory concentrations (MICs) (MIC90 0.03 mg/l and 0.125 mg/l, respectively), remained active against E . rhusiopathiae and should continue to be recommended for treatment . Ciprofloxacin MICs were particularly low (MIC90 0.06 mg/l), offering an alternative agent for the penicillin allergic patient . Erysipelothrix rhusiopathiae is still resistant to vancomycin (MIC90 64 mg/l), highlighting the importance of early diagnosis of E . rhusiopathiae infection in cases of endocarditis . In addition, 31 E . rhusiopathiae isolates were tested against several commercially available home disinfectants . Most were effective in killing E . rhusiopathiae with minimum bactericidal concentrations of 0.001% for Pine O Cleen, and 0.03% for Domestos, Linely and the Wheelie Bin Phenyl Cleanser . CONCLUSIONS: There appeared to be no new emergence of antibiotic resistance in E . rhusiopathiae . Various disinfectants could be used following mechanical cleaning of work environments, such as fishing boats, and equipment, to reduce the risk of infection with E . rhusiopathiae.

Am J Manag Care, 2002 Oct, 8(14 Suppl), S353 - 60
Ototopical agents in the treatment of the draining ear; Denneny JC 3rd; Otorrhea is the result of several pathologic conditions of the ear, including bacterial, fungal, and viral acute external otitis (AOE), acute otitis media with perforation (AOM), posttympanostomy tube otorrhea (PTTO), and chronic suppurative otitis media (CSOM) . The significant differences among these conditions necessitate a thorough knowledge of the pathogenesis of each prior to the selection of a treatment regimen likely to succeed . Consideration must be given to the accelerating process of antimicrobial resistance, rising concern over ototoxicity, and limits on the resources available for healthcare in general . This article reviews the pathophysiology of AOE, AOM, PTTO, and CSOM and proposes treatment options that demonstrate the value of ototopical therapy as the first-line treatment option for AOE, PTTO, and CSOM with consideration given to efficacy as well as cost effectiveness . The growing concern with ototoxicity and resultant recent litigation issues are also discussed.

Bioorg Khim, 2002 Sep-Oct, 28(5), 396 - 401
{Synthesis and antibacterial activity of analogues of the N-terminal fragment of the sarcotoxin IA antimicrobial peptide}; Taran SA et al.; Three 18-membered analogues of the N-terminal fragment of the sarcotoxin IA cationic antimicrobial peptide were synthesized by the solid phase method of peptide synthesis with the use of swellographic monitoring . The ability of these peptides to inhibit the growth of various bacteria in culture medium and their hemolytic activity in experiments on human erythrocytes were studied . The analogue completely corresponding to the N-terminal amino acid sequence of the natural sarcotoxin IA with the amide group on its C-terminus exhibited higher antibacterial activity . The presence of carboxyl group on the C-terminus or the substitution of Tyr for Trp2 resulted in a decrease in the antimicrobial activity of the peptide . Our results indicate that the amphiphilic N-terminal peptide corresponding to the 1-18 sequence of sarcotoxin IA involves the moieties responsible for the antimicrobial activity of the antibiotic.

Am J Kidney Dis, 2002 Nov, 40(5), 886 - 98
Preventing bacterial infections and antimicrobial resistance in dialysis patients; Berns JS et al.; Antimicrobial use, in concert with patient-to-patient transmission of resistant strains, has caused a rapid increase in the prevalence of antimicrobial resistance in recent years . This increase is a particular threat to dialysis patients, who often have been in the forefront of the epidemic of resistance . In this report, which was written in collaboration between the American Society of Nephrology and the Centers for Disease Control and Prevention and has been endorsed by the Executive Council of the Infectious Diseases Society of America, we review and summarize existing clinical practice guidelines and recommendations concerning the prevention, diagnosis, and treatment of certain bacterial infections in dialysis patients and present four strategies to limit the spread of antimicrobial resistance in dialysis patients . First, preventing infection eliminates the need for antimicrobials, thereby reducing selection pressure for resistant strains . Efforts to prevent infection include avoidance of hemodialysis catheters, when possible, and meticulous care of hemodialysis and peritoneal catheters and other hemodialysis vascular access sites . Second, diagnosing and treating infections appropriately can facilitate the use of narrower spectrum agents, rapidly decrease the number of infecting organisms, and reduce the probability of resistance emerging . This entails the collection of indicated specimens for culture and avoidance of contamination of cultures with common skin microorganisms . Third, optimizing antimicrobial use helps protect the efficacy of such critical agents as vancomycin . Published guidelines for the use of vancomycin should be followed, and alternate agents should be used when infections with beta-lactam-resistant bacteria are unlikely or not documented . Fourth, preventing transmission in health care settings is important to limit the spread of resistant organisms . In this regard, such basic measures as glove use and hand hygiene are most important .

J Antimicrob Chemother, 2002 Nov, 50(5), 727 - 9
In vitro activity of sitafloxacin (DU-6859a) alone, or in combination with rifampicin, against Mycobacterium ulcerans; Dhople AM et al.; The antimicrobial effect of sitafloxacin (DU-6859a), used either singly or in combination with rifampicin, was evaluated in vitro against Mycobacterium ulcerans . Growth of M . ulcerans was measured by plate counts and the BACTEC radiometric method . The MICs and MBCs of sitafloxacin for M . ulcerans were in the range 0.125-0.5 mg/L . The values for other fluoroquinolones were two- to four-fold higher than for sitafloxacin . Combination of sitafloxacin and rifampicin exhibited synergy with five of the eight strains, whereas the combination of ofloxacin and rifampicin resulted in additive effects only . These results suggest that the combination of sitafloxacin and rifampicin has potential in the treatment of M . ulcerans infection.

Adv Exp Med Biol, 2002, 512, 141 - 6
Migration of primary and memory CD8 T cells; Lefrancois L et al.; Our results indicate that a substantial proportion of the antimicrobial CD8 and CD4 T cell response is focused in non-lymphoid tissues . This finding makes teleological sense since maximum protection against infection is better served by the widespread presence of effector and memory cells . In the case of CD8 T cells, it appears that irrespective of the site at which initial activation of naive cells occurs, the end result is production of effector cells with broad migratory capabilities . Memory T cells perhaps have more restricted migratory abilities as compared to effector cells, although this needs to be tested definitively . Our results suggest that memory CD8 T cells in the intestinal LP may not be part of the recirculating pool of memory cells, though our data does not preclude the possibility that migrants from outside the mucosa contribute to the LP memory pool . Our data also demonstrates that CD8 memory T cells in non-lymphoid tissue exhibit heightened effector function as compared to their splenic counterparts . Whether these findings indicate the existence of distinct lineages of memory cells remains to be seen . The functional abilities of migrating memory cells could be modulated by the migration process and/or by the environmental milieu of a particular tissue . Although the development of CD8 memory T cells is a complex process requiring multiple signalling pathways, we identified IL-7 as an important player in memory generation . Much further work is needed to decipher the cellular and molecular mechanisms of memory induction as well as to learn the in vivo functional significance of memory cell subsets.

Arzneimittelforschung, 2002, 52(9), 669 - 76
Human neutrophil oxidative bursts and their in vitro modulation by different N-acetylcysteine concentrations; Allegra L et al.; Reactive oxygen species released by activated polymorphonuclear leukocytes as an expression of their defensive function are considered to be a major source of the cytotoxic oxidant stress, that triggers a self-sustaining phlogogenic loop in the respiratory system . N-Acetylcysteine (CAS 616-91-1, NAC), a known mucolytic drug, possesses also antioxidant properties, but it undergoes a rapid and extensive first-pass metabolism resulting in low tissue availability . Thus to further improve the NAC bioavailability a single oral administration of 1200 mg NAC has been recently proposed . This study has been performed to investigate in vitro by means of luminol amplified chemiluminescence the ability of the concentration of 35 mumol/l NAC available after single oral administration of 1200 NAC to interfere with human neutrophil oxidative burst evoked by both corpuscolate and soluble stimulants, in comparison with 16 mumol/l NAC, the serum concentration obtainable after single oral administration of 600 mg NAC . At concentrations of 16 and 35 mumol/l, NAC significantly reduced in a concentration-dependent manner the activation of polymorphonuclear neutrophils (PMNs) oxidative bursts induced by all of the stimulants (C . albicans, formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA)) . This effect was also present in cell-free systems, thus confirming the scavenger activity of these two concentrations of NAC . The fact that no effects were seen on PMN phagocytosis and bacterial killing indicates that NAC has no negative influence on other PMN functions such as antimicrobial activity.

Nippon Ronen Igakkai Zasshi, 2002 Sep, 39(5), 545 - 8
{A case of Parkinson's disease associated with pyogenic spondylitis in the cervical vertebrae}; Imamura K et al.; A 68-year-old woman with Parkinson's disease (PD) was admitted due to aspiration pneumonia . The symptoms improved partly by administration of antimicrobial agents and a steroid-pulse treatment, but she suffered repeated MRSA pneumonia, which caused a long-term bed confinement . Shoulder pain that appeared after she started rehabilitation did not improve on administration of NSAIDs . We suspected pyogenic spondylitis in the cervical vertebraes based on the cervical X-rays and the cervical MRI . Patients of PD often have a shoulder pain due to various causes . When a patient with PD has a severe shoulder pain, we should suspect pyogenic spondylitis in the cervical vertebraes as one of the differential diagnoses . It is necessary to do immediately thorough imaging examinations.

Chembiochem, 2002 Nov 4, 3(11), 1126 - 33
Macrocyclic hairpin mimetics of the cationic antimicrobial peptide protegrin I: a new family of broad-spectrum antibiotics; Shankaramma SC et al.; The problems associated with increasing antibiotic resistance have stimulated great interest in newly discovered families of naturally occurring cationic antimicrobial peptides . These include protegrin, tachyplesin, and RTD-1, which adopt beta-hairpin-like structures . We report here an approach to novel peptidomimetics based on these natural products . The mimetics were designed by transplanting the cationic and hydrophobic residues onto a beta-hairpin-inducing template, either a D-Pro-L-Pro dipeptide or a xanthene derivative . The mimetics have good antimicrobial activity against Gram-positive and Gram-negative bacteria (minimal inhibitory concentration approximately 6-25 microgram mL(-1)) . Analogues with improved selectivity for microbial rather than red blood cells (1 % hemolysis at 100 microgram mL(-1)) were identified from a small library prepared by parallel synthesis . Thus, it is possible to separate the antimicrobial and hemolytic activities in this class of mimetics . NMR studies on one mimetic revealed a largely unordered structure in water, but a transition to a regular beta-hairpin backbone conformation in the presence of dodecylphosphocholine micelles . This family of mimetics may provide a starting point for the optimization of antimicrobial agents of potential clinical value in the fight against multiple-drug-resistant microorganisms.

Biochemistry, 2002 Nov 5, 41(44), 13309 - 17
Crystal structure of a ternary complex of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase: NAD+ orients the active site loop for catalysis; Gan L et al.; Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the conversion of IMP to XMP with the reduction of NAD(+), which is the rate-limiting step in the biosynthesis of guanine nucleotides . IMPDH is a promising target for chemotherapy . Microbial IMPDHs differ from mammalian enzymes in their lower affinity for inhibitors such as mycophenolic acid (MPA) and thiazole-4-carboxamide adenine dinucleotide (TAD) . Part of this resistance is determined by the coupling between nicotinamide and adenosine subsites in the NAD(+) binding site that is postulated to involve an active site flap . To understand the structural basis of the drug selectivity, we solved the X-ray crystal structure of the catalytic core domain of Tritrichomonas foetus IMPDH in complex with IMP and beta-methylene-TAD at 2.2 A resolution . Unlike previous structures of this enzyme, the active site loop is ordered in this complex, and the catalytic Cys319 is 3.6 A from IMP, in the same plane as the hypoxanthine ring . The active site loop forms hydrogen bonds to the carboxamide of beta-Me-TAD which suggests that NAD(+) promotes the nucleophillic attack of Cys319 on IMP . The interactions of the adenosine end of TAD are very different from those in the human enzyme, suggesting the NAD(+) site may be an exploitable target for the design of antimicrobial drugs . In addition, a new K(+) site is observed at the subunit interface . This site is adjacent to beta-Me-TAD, consistent with the link between the K(+) activation and NAD(+) . However, contrary to the coupling model, the flap does not cover the adenosine subsite and remains largely disordered.

Vet Rec, 2002 Sep 28, 151(13), 371 - 2
Antibiotic resistance--an evolving problem; Wise R et al.; In 1998, an influential report on antimicrobial resistance from the House of Lords Select Committee on Science and Technology highlighted the threat posed to public health by resistance, and called for products to be used more prudently in both human and veterinary medicine . Here, Lord Soulsby, who chaired the Lords' committee on antimicrobials, and Richard Wise, who advised the committee and is now chairman of the Government's Specialist Advisory Committee on Antimicrobial Resistance, consider what has been achieved since then, along with the challenges that remain.

Acta Pol Pharm, 2002 Jul-Aug, 59(4), 291 - 3
Synthesis, structural characterization and antimicrobial studies of hydrazone derivatives of 3-hydroxyimino-5-methyl-2-hexanone; Donde KJ et al.; The derivatives of 3-hydroxyimino-5-methyl-2-hexanone oxime have been obtained in good yield by its reactions either with hydrazine hydrate or phenyl hydrazine, respectively . IR and 1H NMR spectral data of these compounds have been discussed . All the newly synthesised compounds have been tested for their biological activity against S . auerus, S . typhi, C . albicans, A . niger, S . cerevisiae and M . tuberculosis H47RV.

J Med Assoc Thai, 2002 Aug, 85 Suppl 2, S682 - 9
Mycobacterium avium complex in HIV-infected Thai children; Phongsamart W et al.; Of the 169 human immunodeficiency virus (HIV)-infected children being cared for at Siriraj Hospital from January 1998 to September 2000, 10 had Mycobacterium avium complex (MAC) infection; seven had disseminated disease and three had MAC pneumonia . Nine children were in the advanced stage of HIV disease at the time of diagnosis with the median CD4 count of 7 cells/mm3 and 127 cells/mm3 and the median age of 65 months and 63 months in disseminated MAC and MAC pneumonia respectively . None of these children had received prior chemoprophylaxis . Common clinical findings included prolonged fever, weight loss, lymphadenopathy, hepatosplenomegaly, diarrhea, anemia and leukopenia . The outcome of MAC infection was poor, with a mortality rate of 60 per cent . In in vitro susceptibility testing, clarithromycin was the least resistant drug . With the incidence rate of 2.15 per 100 person-years, the high rate of antimicrobial resistance, and the poor outcome, primary chemoprophylaxis for MAC infection in conjunction with effective antiretroviral therapy should be considered for Thai children in the advanced stage of HIV infection.

J Clin Pathol, 2002 Nov, 55(11), 817 - 23
Imaging bacterial infection with (99m)Tc-ciprofloxacin (Infecton); Britton KE et al.; AIMS: The diagnosis of deep seated bacterial infections, such as intra-abdominal abscesses, endocarditis, and osteomyelitis, can be difficult and delayed, thereby compromising effective treatment . This study assessed the efficacy of a new radioimaging agent, Tc-99m ciprofloxacin (Infecton), in accurately detecting sites of bacterial infection . METHODS: Eight hundred and seventy nine patients with suspected bacterial infection underwent Infecton imaging and microbiological evaluation . The sensitivity and specificity of Infecton in detecting sites of bacterial infection were determined with respect to Centres of Disease Control, World Health Organisation, and Dukes's criteria . RESULTS: Five hundred and seventy four positive and 295 negative images were produced . These included 528 true positives, 46 false positives, 205 true negatives and 90 false negatives, giving an overall sensitivity of 85.4% and a specificity of 81.7% for detecting infective foci . Sensitivity was higher (87.6%) in microbiologically confirmed infections . CONCLUSIONS: Infecton is a sensitive technique, which aids in the earlier detection and treatment of a wide variety of deep seated bacterial infections . The ability to localise infective foci accurately is also important for surgical intervention, such as drainage of abscesses . In addition, serial imaging with Infecton might be useful in monitoring clinical response and optimising the duration of antimicrobial treatment.

Curr Biol, 2002 Oct 15, 12(20), 1728 - 37
A ubiquitin-proteasome pathway represses the Drosophila immune deficiency signaling cascade; Khush RS et al.; BACKGROUND: The inducible production of antimicrobial peptides is a major immune response in Drosophila . The genes encoding these peptides are activated by NF-kappaB transcription factors that are controlled by two independent signaling cascades: the Toll pathway that regulates the NF-kappaB homologs, Dorsal and DIF; and the IMD pathway that regulates the compound NF-kappaB-like protein, Relish . Although numerous components of each pathway that are required to induce antimicrobial gene expression have been identified, less is known about the mechanisms that either repress antimicrobial genes in the absence of infection or that downregulate these genes after infection . RESULTS: In a screen for factors that negatively regulate the IMD pathway, we isolated two partial loss-of-function mutations in the SkpA gene that constitutively induce the antibacterial peptide gene, Diptericin, a target of the IMD pathway . These mutations do not affect the systemic expression of the antifungal peptide gene, Drosomycin, a target of the Toll pathway . SkpA encodes a homolog of the yeast and human Skp1 proteins . Skp1 proteins function as subunits of SCF-E3 ubiquitin ligases that target substrates to the 26S proteasome, and mutations affecting either the Drosophila SCF components, Slimb and dCullin1, or the proteasome also induce Diptericin expression . In cultured cells, inhibition of SkpA and Slimb via RNAi increases levels of both the full-length Relish protein and the processed Rel-homology domain . CONCLUSIONS: In contrast to other NF-kappaB activation pathways, the Drosophila IMD pathway is repressed by the ubiquitin-proteasome system . A possible target of this proteolytic activity is the Relish transcription factor, suggesting a mechanism for NF-kappaB downregulation in Drosophila.

Ann Thorac Surg, 2002 Oct, 74(4), 1195 - 200
A retrospective review of three antibiotic prophylaxis regimens for pediatric cardiac surgical patients; Maher KO et al.; BACKGROUND: Optimal antimicrobial prophylaxis for the pediatric cardiac surgical patient is unknown . We have reviewed our experience with more than 4,000 pediatric cardiac surgical patients at the University of Michigan to evaluate antibiotic prophylaxis regimens . METHODS: Three antibiotic prophylaxis protocols were serially used during a 6-year period: Protocol 1 (n = 786): cefazolin was administered before operation and continued as long as thoracostomy tubes or central venous catheters were present; Protocol 2 (n = 1095): cefazolin was discontinued 48 hours postoperatively, regardless of the presence of tubes or catheters; Protocol 3 (n = 2039): cefazolin was continued as long as thoracostomy tubes were present, but not for central venous catheters . Patients with an open chest postoperatively received vancomycin and gentamicin until chest closure . This was identical during all three protocols . We retrospectively determined the rate of surgical site infections and unrelated bloodstream infections (the latter for both cardiac medical and surgical patients) for the three protocols . RESULTS: Surgical site infections per 100 operations for protocols 1, 2, and 3 was 2.04, 6.58, and 1.67, respectively (p < 0.05 for protocol 2 versus protocols 1 and 3) . The mean age of patients with a surgical site infection ranged from 12 to 15.4 months . Patients with an open chest had a higher rate of surgical site infection (18.8% for protocol 2 and 9.3% for protocol 3) . Bloodstream infections per 1,000 patient days for protocols 1, 2, and 3 were 2.18, 6.51, and 5.02, respectively (p < 0.05 protocol 1 versus protocols 2 and 3) . CONCLUSIONS: These data suggest that pediatric cardiac surgical patients may benefit from prophylactic antibiotics as long as thoracostomy tubes are in place.

Biosci Biotechnol Biochem, 2002 Sep, 66(9), 1848 - 52
Interactions of a lysozyme-monomethoxypolyethylene glycol conjugate with lipopolysaccharides and lipid bilayers and effects of conjugate on gram-negative bacteria; Nodake Y et al.; We have been studying a lysozyme derivative, called mPEG-lysozyme, in which Lys 33 is bound with a monomethoxypolyethylene glycol derivative . Here, we examined the surface hydrophobicity of the derivative and also its interactions with lipopolysaccharides and lipid bilayers . These properties may affect the antimicrobial activity of mPEG-lysozyme toward Gram-negative microorganisms . The lysozyme derivative had more than 150% of the antimicrobial activity for such microorganisms with that of native lysozyme taken to be 100% . Spectroscopic analyses indicated that mPEG-lysozyme bound to lipopolysaccharides with higher affinity than lysozyme, because of the high surface hydrophobicity of the derivative . In an experiment on carboxyfluorescein-leakage, mPEG-lysozyme strongly interacted with liposomes constructed from phosphatidylcholine, releasing carboxyfluorescein from the liposomes more effectively than lysozyme did . mPEG-lysozyme may perturb the outer membrane of Gram-negative microorganisms, gaining itself access to the peptidoglycan layers of the bacterium.

J Biol Chem, 2002 Dec 27, 277(52), 50450 - 6 Epub 2002 Oct 23.
Correlations of cationic charges with salt sensitivity and microbial specificity of cystine-stabilized beta -strand antimicrobial peptides; Tam JP et al.; The electrostatic interaction of the charge cluster of an amphipathic peptide antibiotic with microbial membranes is a salt-sensitive step that often determines organism specificity . We have examined the correlation between charge clusters and salt insensitivity and microbial specificity in linear, cyclic, and retro-isomeric cystine-stabilized beta-strand (CSbeta) tachyplesin (TP) in a panel of 10 test organisms . Cyclic tachyplesins consisting of 14 and 18 amino acids are constrained by an end-to-end peptide backbone and two or three disulfide bonds to cross-brace the anti-parallel beta-strand that approximates a "beta-tile" structure . Circular dichroism measurements of beta-tile TPs showed that they displayed ordered structures . Control peptides containing the same number of basic amino acids as TP but lacking disulfide constraints were highly salt sensitive . Cyclic TP analogues with six cationic charges were more broadly active and salt-insensitive than those with fewer cationic charges . Reducing their proximity or number of cationic charges, particularly those with three or fewer basic amino acids, led to a significant decrease in potency and salt insensitivity, but an increased selectivity to certain Gram-positive bacteria . An end-group effect of the dibasic N-terminal Lys of TP in the open-chain TP and its retroisomer was observed in certain Gram-negative bacteria under high-salt conditions, an effect that was not found in the cyclic analogs . These results suggest that a stable folded structure together with three or more basic amino acids closely packed in a charged region in CSbeta peptides is important for salt insensitivity and organism specificity.

J Control Release, 2002 Nov 7, 84(1-2), 69 - 78
A facile method of delivery of liposomes by nebulization; Desai TR et al.; In this study, we have demonstrated a facile approach to the aerosol delivery of liposomes by nebulization . The approach involves mere dispersion of the physical mixture of phospholipid(s) and drug in saline, which results in spontaneous formation of liposomes thereby creating reservoirs for the encapsulation of drugs . Various phospholipids exhibiting different physico-chemical properties were investigated here . Two antimicrobial agents (ciprofloxacin and CM3, a novel peptide) and a bronchodilator, salbutamol sulfate, were used as model drugs to examine the nebulization properties . Nebulization properties were found to be dependent upon the nature of the phospholipids and drug . Among various phospholipids investigated, dimyristoyl phosphatidyl glycerol (DMPG), a combination of egg phosphatidylcholine (EPC) plus DMPG (i.e., EPC+DMPG) and dimyristoyl phosphatidylcholine (DMPC) plus DMPG (DMPC+DMPG) (molar ratios 1:1) showed encouraging results in terms of higher nebulization efficiency and lower leakage of drug after nebulization . The generated aerosols were characterized by an Andersen cascade impactor operated at 28.3 l/min . The mass median aerodynamic diameter (MMAD) values of the aerosol droplets obtained by nebulization of all the preparations containing DMPG reveal that these preparations are suitable for aerosol delivery by nebulization . This facile approach is expected to overcome problems associated with stability upon storage and high production costs.

J Nat Prod, 2002 Oct, 65(10), 1387 - 90
Neoclerodane and labdane diterpenoids from Plectranthus ornatus; Rijo P et al.; Three new diterpenoids, a neoclerodane and two labdane derivatives, have been isolated from an acetone extract of Plectranthus ornatus . The structures of these compounds (plectrornatins A-C, 1-3, respectively) were established mainly by spectroscopic means, particularly by 1D and 2D NMR studies and, in the case of the neoclerodane 1, by an X-ray diffraction analysis . Compounds 1 and 3 showed moderate antimicrobial activity against five Candida species and selected Gram negative and Gram positive bacteria strains.

Int J Med Microbiol, 2002 Sep, 292(3-4), 277 - 82
Expanded spectrum of Nocardia species causing clinical nocardiosis detected by molecular methods; Wellinghausen N et al.; Nocardia species isolated from seven patients with clinical infection were investigated by conventional biochemical methods and 16S rRNA gene sequencing . Three isolates were identified as recently described species (i.e., N . paucivorans, N . abscessus and N . veterana) . We provide data on the epidemiology, clinical significance and antimicrobial susceptibility of these newly described Nocardia species.

J Interferon Cytokine Res, 2002 Sep, 22(9), 913 - 22
Role of blood platelets in infection and inflammation; Klinger MH et al.; Blood platelets are here presented as active players in antimicrobial host defense and the induction of inflammation and tissue repair in addition to their participation in hemostasis . Megakaryopoiesis is inhibited after acute infection with viruses or bacteria . In contrast, chronic inflammation is often associated with reactive thrombocytosis . Platelets can bind and internalize pathogens and release microbicidal proteins that kill certain bacteria and fungi . By making cell-cell contacts with leukocytes and endothelial cells, platelets assist white blood cells in rolling, arrest and transmigration . On stimulation by bacteria or thrombin, platelets release the content of their alpha-granules, which include an arsenal of bioactive peptides, such as CC-chemokines and CXC-chemokines and growth factors for endothelial cells, smooth muscle cells and fibroblasts . Thus, integral to innate immunity, the tiny little platelets may become bombshells when irritated by pathogens.

J Pharm Pharmacol, 2002 Oct, 54(10), 1399 - 405
Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide release; Chiou WF et al.; Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti-inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production . Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg(-1), i.v.) for 6 h showed a severe decrease in mean arterial pressure . This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO2- plus NO3-) . Pretreatment with ethanol extract of E . rutaecarpa (25, 50 and 100 mg kg(-1), i.v.), 1 h before LPS, dose-dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over-production in plasma in endotoxaemic rats . A selective inducible NO-synthase (iNOS) inhibitor, aminoguanidine (15 mg kg(-1), i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached . Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E . rutaecarpa pretreatment . In summary, E . rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO . These significant results may offer E . rutaecarpa as a candidate for the treatment of this model of endotoxaemia.

Toxicol In Vitro, 2002 Oct, 16(5), 499 - 508
The in vitro effects of Pb acetate on NO production by C6 glial cells; Garber MM et al.; The CNS neurotoxic effects of lead (Pb) are well documented; however, the molecular toxicity targets have not been clearly delineated . Astroglial cells, which are the most abundant cells in the brain and provide critical support to the neurons, are known to accumulate Pb . Although NO generated by inducible NO synthase (iNOS) in glial cells has been associated with many neurotoxic events, it can also serve to protect by modulating blood flow, increase antimicrobial and tumoricidal activities, and promote immune responses following injury or insult . The present investigations were designed to test the hypothesis that Pb exposure may perturb cytokine signal transduction pathways leading to NO production by astroglial cells . Pretreatment with Pb acetate (500 nM-10 microM) attenuated the generation of NO in a concentration-dependent manner up to 90%, and suppressed iNOS protein expression, as well as interfered with the homeostatic functions of calcium in the cytokine-induced NO signal transduction pathway . In addition, pretreatment with staurosporine, a serine-threonine kinase inhibitor, or KT5720, a specific protein kinase A inhibitor (PKA), inhibited cytokine-induced NO production in a concentration-dependent manner with IC(50) values of 26.3 and 346.7 nM, respectively . Therefore, Pb may impede events within the PKA signal transduction pathway; although, based on results from a gel shift assay, Pb does not directly affect PKA enzyme activity . Taken together, these results suggest the possibility that the suppressive effect of Pb acetate on cytokine-induced NO production in glial cells may be implicated in the neurophysiologic changes noted following occupational or environmental exposure to Pb.

J Mol Med, 2002 Oct, 80(10), 678 - 84 Epub 2002 Sep 19.
Dynamic alteration of human beta-defensin 2 localization from cytoplasm to intercellular space in psoriatic skin; Huh WK et al.; Defensins are cationic antimicrobial peptides with a broad spectrum . Recently human beta-defensin 2 (hBD-2) has been isolated from psoriatic skin; however, its exact localization and fate have not been fully understood . We studied the distribution pattern of hBD-2 in skin tissues of psoriasis and other inflammatory skin diseases . In the upper spinous and granular layer of psoriasis vulgaris hBD-2 was present in the cytoplasm . In the horny layer the positive signals were in a basket-weave pattern, indicating possible accumulation of hBD-2 in the intercellular space . The similar pattern of hBD-2 distribution was observed in the lesions of nummular eczema and atopic dermatitis . hBD-2 was not detected in the section of normal elbow and knee skin . When isolated psoriatic scales were stained, hBD-2 was detected in a wrapping paper-like distribution pattern surrounding the corneocytes . In horny layer of psoriatic skin hBD-2 was closely associated or colocalized with elafin, which is known to be in extracellular space, as demonstrated by double staining . Western blot analysis using cultured human keratinocytes detected hBD-2 with an expected size in the conditioned medium and in the cell lysates when stimulated with 5% FCS or IL-alpha . These results indicate that hBD-2 was synthesized and remained in cytoplasm in the upper spinous and granular layer, and then secreted into intercellular space in the horny layer . This dynamic change in hBD-2 distribution in epidermis is certainly relevant to function as an innate host defense mechanism against invading micro-organisms.

Crit Care Med, 2002 Oct, 30(10), 2278 - 83
New model of ventilator-associated pneumonia in immunocompetent rabbits; Charles PE et al.; OBJECTIVE: Despite the high rate of therapeutic failures in ventilator-associated pneumonia, up to now there has been no animal model specifically designed for antimicrobial evaluation . A rabbit model of ventilator-associated pneumonia is described for the first time in this study.DESIGN Prospective, randomized experimental study . SETTING: An animal research laboratory . SUBJECTS: Male New Zealand healthy rabbits (n = 44) . INTERVENTIONS: After oral intubation and an hour of mechanical ventilation, animals in the ventilator-associated pneumonia group (n = 22) were infected intrabronchially with a calibrated inoculum of . The nonventilated pneumonia group (n = 22) was composed of animals that received the same inoculum in the absence of mechanical ventilation . Rabbits from both groups were randomly killed 3, 6, 12, 24, or 48 hrs after inoculation . Pneumonia evaluation was based on histologic (macroscopic and microscopic score) and bacteriologic (bacterial count) findings . MAIN RESULTS: Infected animals undergoing mechanical ventilation rapidly developed a progressive bilateral and multifocal pneumonia . Lung bacterial mean (sd) concentration was 6.48 (0.71) log10 colony-forming units (cfu) per gram of tissue at the 48th hour, whereas bacteremia occurred in most cases . In the nonventilated pneumonia group, pneumonia was less severe in terms of bacterial count (3.18 {1.86} log10 cfu/g; p <.05), and spleen cultures remained negative . In addition, microscopic examination revealed noninfectious lung injury in the ventilator-associated pneumonia group, especially hyaline membrane filling alveolar spaces . Of note, these features were never observed in the nonventilated pneumonia group . CONCLUSIONS: An animal model of ventilator-associated pneumonia was obtained in immunocompetent rabbits . Histopathologic and bacteriologic features were similar to those found in humans . Obviously, pneumonia was more severe when animals underwent mechanical ventilation, especially in terms of systemic spread . Noninfectious lung injury corresponding to ventilation-induced lung injury may explain the difference . This model emphasizes the strong impact of both mechanical ventilation and infection on lung because they seem to act synergistically when causing alveolar damage . Moreover, it seems well suited to testing antimicrobial effectiveness.

Pediatr Infect Dis J, 2002 Oct, 21(10), 935 - 40
Clinical implications of inducible beta-lactamase activity in Gram-negative bacteremia in children; Boyle RJ et al.; BACKGROUND: Organisms of the spp., indole-positive spp., spp . and (ESCaPPM) group are a common cause of hospital-acquired bacteremia and share the potential to develop beta-lactam resistance during therapy . The emergence of such resistance may have adverse consequences, but the frequency with which this occurs has not been studied in children . It has been suggested that such organisms should be treated with combination antimicrobials or carbapenems, but the optimal regimen is uncertain.AIM To determine the frequency with which beta-lactam resistance develops during ESCaPPM sepsis in children and the optimal treatment of such sepsis . METHODS: A review of the case notes and microbiologic records of all cases of ESCaPPM bacteremia and meningitis managed at a tertiary children's hospital during a 6-year period . RESULTS: Fifty-eight cases were identified, and in three (5%) cases beta-lactam resistance emerged during treatment, with adverse clinical consequences in two cases . Clinical and microbiologic outcome was similar in those treated with carbapenems and in those treated with a beta-lactam and aminoglycoside combination . Cefotaxime resistance was found in 57, 30, 24 and 7% of children who had received carbapenems, cephalosporins, penicillins or no/other antimicrobials in the month before ESCaPPM sepsis, respectively . CONCLUSIONS: The emergence of beta-lactam resistance during treatment of ESCaPPM sepsis is uncommon in our hospital but can have adverse consequences . Where isolates are reported as susceptible to both classes of drugs, an extended spectrum penicillin in combination with an aminoglycoside may be preferable first line treatment of ESCaPPM sepsis to a carbapenem or quinolone.

J Pediatr Gastroenterol Nutr, 2002 Oct, 35(4), 564 - 9
Antimicrobial prophylaxis for gastrointestinal procedures: current practices in North American academic pediatric programs; Snyder J et al.; BACKGROUND: Guidelines for the use of antibiotic prophylaxis in children are based on a small number of studies that assess the risk of infection associated with performing endoscopic procedures . The American Heart Association (AHA) and the American Society of Gastroenterological Endoscopy (ASGE) have established guidelines that identify conditions and procedures that place a child at greater risk for infectious complications . Because data on bacteremia and sepsis associated with endoscopy in children are very limited, we reviewed the practices of 15 large academic pediatric gastroenterology services to see if patterns of practice and safety could be determined . METHODS: A questionnaire was sent to 15 academic gastroenterology centers in the United States and Canada asking about antibiotic prophylaxis for endoscopic procedures for children with six conditions . These included three conditions related to congenital heart disease based on negligible, moderate, and high risk for endocarditis; immune compromise; the presence of a central venous line; and the presence of a ventriculo-peritoneal shunt . Six procedures were evaluated, including esophagogastroduodenoscopy with biopsy, flexible sigmoidoscopy or colonoscopy with biopsy, endoscopic retrograde cholangiopancreatography, esophageal sclerotherapy, esophageal dilation, and percutaneous endoscopic gastrostomy (PEG) tube placement . RESULTS: The patterns of reported practice generally conform to the AHA and ASGE guidelines . The six conditions and six procedures yielded 36 response categories for the participating centers . The majority of centers reported routine use of antibiotic prophylaxis in about half (17) of the response categories, which represented three distinct situations . These included children with congenital heart disease having moderate or high risk for bacterial endocarditis for almost all procedure categories and children undergoing PEG tube placement regardless of underlying condition . In all other combinations of underlying conditions and procedures, the majority of centers did not use routine prophylaxis . The majority of centers did not use antibiotic prophylaxis for cardiac conditions with a negligible risk of infectious complication or for children with immunocompromise, central venous lines, or ventriculo-peritoneal shunts for any procedure except PEG placement . CONCLUSIONS: These results indicate that the routine use of antibiotic prophylaxis is limited in pediatric academic centers to a few very specific conditions and procedures . The results also provide indirect evidence that the risk of infectious complications associated with endoscopic procedures appears to be exceedingly low.

J Clin Invest, 2002 Oct, 110(8), 1151 - 63
mRNA expression profiles for Escherichia coli ingested by normal and phagocyte oxidase-deficient human neutrophils; Staudinger BJ et al.; To gain a better understanding of bacterial responses to complex and hostile environments generated within the neutrophil phagosome, we estimated mRNA abundance, using genomic arrays, in Escherichia coli cells ingested by normal and phagocyte oxidase-deficient human neutrophils . Genes regulated by the oxidant sensing transcription factor OxyR were among those strongly induced upon phagocytosis by normal, but not oxidase-deficient, neutrophils . Several genes related to nitrogen metabolism, especially those regulated by the NtrC and NAC proteins and transcribed via the varsigma(54) alternative sigma factor, were suppressed by both normal and oxidase-deficient neutrophils . A DeltaoxyRS mutant strain of E . coli was significantly more susceptible than the parent strain to neutrophil-mediated killing, which suggests that OxyR-regulated gene products contribute a measure of resistance to neutrophil antimicrobial systems . The hypersusceptibility of the DeltaoxyRS mutant was attenuated when oxidase-deficient neutrophils were employed, suggesting that much of the protection afforded by the OxyR regulon is against oxidative antimicrobial factors . Expression profiling of phagocytosed bacteria appears to provide useful information about conditions in the phagocytic vacuole and about bacterial defenses mounted in response to this hostile environment.

Int J Pediatr Otorhinolaryngol, 2002 Nov 11, 66(2), 149 - 53
Bacteremia during adenoidectomy; Okur E et al.; OBJECTIVE: Although adenoidectomy is one of the most commonly performed surgical procedures in children, there is no satisfactory information about the risk of bacteremia during adenoidectomy and necessity of antibiotic use . The aim of this study was to determine the incidence of bacteremia during adenoidectomy and identify the organisms leading to bacteremia . METHODS: Thirty two patients who had undergone adenoidectomy at ENT Clinic of Sutcu Imam University were included in the study . They had received no antimicrobial therapy for at least 20 days before surgery . Adenoidal surface and deep tissue cultures were taken and venous blood samples were obtained for cultures before and immediately after adenoidectomy in which adenoid was removed with a curette . RESULTS: While none of the blood cultures taken preoperatively was positive for any organisms, the cultures obtained postoperatively were positive in only two of 32 patients included in the study . CONCLUSION: The results of this study suggest that there is an extremely low incidence of bacteremia during adenoidectomy . As a result, it may be concluded that the use of prophylactic antibiotics to prevent bacteremia or its complications is unnecessary unless the patient has a predisposing factor for cardiac infection like prosthetic valve replacement .

J Hosp Infect, 2002 Oct, 52(2), 88 - 92
Molecular epidemiology of Stenotrophomonas maltophilia in a university hospital; Crispino M et al.; The aim of this investigation was to study the molecular epidemiology of Stenotrophomonas maltophilia in a university hospital in Italy . Sixty-one clinical isolates were collected from 43 patients during a two-year period . The majority of specimens were from the respiratory tract (41 of 43) of patients in the adult intensive care unit (ICU) (19 of 43) or cystic fibrosis (CF) patients (13 of 43) . Genotypic analysis by pulsed-field gel electrophoresis (PFGE) of clinical isolates identified 31 different PFGE patterns . Although most patients were infected or colonized by different S . maltophilia clones, clones with identical genotype were isolated in patients from ICU, where two separate outbreaks were identified . Antimicrobial susceptibility identified a multi-resistant phenotype in all S . maltophilia PFGE clones . The majority of PFGE clones identified (six of seven clones from patients in the ICU) were susceptible to fluoroquinolones . Mechanical ventilation was associated with S . maltophilia acquisition in the ICU .

J Appl Microbiol, 2002, 93(5), 765 - 71
Antimicrobial activity of methyl cis-7-oxo deisopropyldehydroabietate on Botrytis cinerea and Lophodermium seditiosum: ultrastructural observations by transmission electron microscopy; Feio SS et al.; AIMS: To study the antifungal activity of methyl cis-7-oxo-deisopropyldehydroabietate (MCOD) against phytopathogenic fungi, Botrytis cinerea and Lophodermium seditiousm . The effect of the compound was studied by transmission electron microscopy (TEM) and the composition of sterols on both treated and untreated cultures was determined . METHODS AND RESULTS: MCOD was tested at concentrations in the range 0.003-0.5% by the agar plate dilution method . The radial growth of the colonies treated with MCOD was measured against colonies from untreated cultures . The radial growth of colonies of both fungi and the spore germination of B . cinerea were partially or completely inhibited . Fragments of active growing colonies treated and untreated with MCOD were submitted to the conventional procedure for ultrastructural observation by TEM . Observations by TEM on colonies of B . cinerea and L . seditiosum under 0.1% MCOD revealed several autophagic-like vacuoles, morphological alterations on lomasome and lipid accumulations in the apical zone of hyphae of both fungi . Observations on spore germination of B . cinerea revealed the presence of strongly stained lipid accumulations retained by vacuoles at the cell periphery of young hyphae . The sterol composition of B . cinerea and L . seditiosum was determined on MCOD treated and untreated cultures by gas-chromatography/mass-spectrometry (GC-MS) with molecular ions and fragmentation patterns characteristics of ergosterol (M+396) and dihydroergosterol (M+398) in both fungi . CONCLUSIONS: The morphological alterations are consistent with an unspecific mode of action of MCOD causing inhibition of normal growth or damaging the fungi cells . TEM observations suggest a mechanism of resistance based on the retention of MCOD by the lipid accumulation . SIGNIFICANCE AND IMPACT OF THE STUDY: The results obtained in the present work afforded a better understanding of the mode of action of a resin acid derivative on phytopathogenic fungi . The inhibition growth of both fungi by MCOD demonstrates the antifungal activity of this compound and the interest on further in vivo studies, in order to evaluate its potential as a benign alternative to conventional fungicides.

Planta Med, 2002 Oct, 68(10), 941 - 3
Composition and antimicrobial activity of the essential oil of Achillea multifida; Baser KH et al.; The composition of the water-distilled essential oil of Achillea multifida (DC.) Boiss . (Compositae) was analysed by GC and GC/MS . Fifty-eight compounds were identified representing 93.9 % of the total oil . alpha-Thujone (60.9 %), beta-thujone (9.1 %), sabinene (4.1 %) and camphor (3.7 %) were characterised as the main constituents . The essential oil was tested for its antimicrobial activity using a micro-dilution assay resulting in the inhibition (MIC: 62.5-250 microg/ml) of human pathogenic bacteria and yeast.

J Clin Periodontol, 2002 Aug, 29(8), 736 - 42
In vitro antimicrobial susceptibility of oral strains of Actinobacillus actinomycetemcomitans to seven antibiotics; Muller HP et al.; BACKGROUND/AIMS: Periodontal infections with Actinobacillus actinomycetemcomitans seem to be refractory to conventional therapy . The aim of the present study was to test the in vitro susceptibilities of A . actinomycetemcomitans strains to a panel of seven orally administrable antibiotics . METHODS: A total of 60 isolates of A . actinomycetemcomitans recovered from 43 individuals with gingivitis or periodontitis were tested . In addition, laboratory strains UP-6 and JP2 were analysed . The E-test was employed in order to determine minimal inhibitory concentrations (MIC) of antibiotics ampicillin/sulbactam, roxithromycin, azithromycin, doxycycline, metronidazole, ciprofloxacin, and moxifloxacin . RESULTS: A . actinomycetemcomitans was highly susceptible to both fluoro-quinolones (MIC90 of 0.006 microgram/mL of ciprofloxacin and 0.032 microgram/mL of moxifloxacin) . Good susceptibilities were found for ampicillin/sulbactam and doxycycline (MIC90 of 0.75 microgram/mL and 1 microgram/mL, respectively), and moderate susceptibilities for azithromycin (MIC90 of 3 microgram/mL) . Most strains were resistant to metronidazole and roxithromycin . Cluster analysis revealed two larger clusters of A . actinomycetemcomitans strains with the smaller cluster assembling isolates with significantly higher MICs of most antibiotics . CONCLUSIONS: Due to reported favourable pharmacokinetics, the fluoro-quinolone moxifloxacin appeared to be a promising candidate for adjunctive systemic antibiotic therapy in periodontal infections with A . actinomycetemcomitans.

Lett Appl Microbiol, 2002, 35(5), 385 - 9
Preservative properties of Calamintha officinalis essential oil with and without EDTA; Nostro A et al.; AIMS: This study was focused on the preserving properties of Calamintha officinalis essential oil, a plant known for its diaphoretic, expectorant and aromatic properties . METHODS AND RESULTS: The commercial aerial parts of C . officinalis Moench were hydrodistilled and the essential oil analysed by Gas chromatography/Electron impact mass spectrometry (GC/EIMS) . The inhibition efficacy of this essence, alone (0.5 and 1.0% v/v) and in combination with 2.0 mM EDTA, was assayed, in culture medium and in cetomacrogol cream, using preservative efficacy testing against standard microrganisms (E . coli ATCC 25922, Ps . aeruginosa ATCC 9027, Staph . aureus ATCC 6538P, C . albicans ATCC 10231 and A . niger ATCC 16404) . C . officinalis essential oil in cetomacrogol cream with EDTA showed long-lasting antimicrobial activity, satisfying the European Pharmacopoeia Commission (E . P.) criteria . CONCLUSION: C . officinalis essential oil could have a potential for a future use as a cosmetic preservative . IMPACT OF THE STUDY: To find natural compounds with antimicrobial activity which could be alternatives to the synthetic chemical preservatives.

Helicobacter, 2002 Oct, 7(5), 322 - 6
A case of acute gastric mucosal lesions associated with Helicobacter heilmannii infection; Yoshimura M et al.; A 69-year-old-woman presented with acute epigastric pain, nausea, vomiting and heartburn . Endoscopy disclosed acute gastric mucosal lesions including mucosal edema, erosions, and ulcers with blood crusts in the antrum . Touch cytology and histological assessment obtained from the affected mucosa revealed acute neutrophilic gastritis and single longer and more coiled organisms than Helicobacter pylori, suggesting Helicobacter heilmannii . Electron micropragh confirmed the characteristic morphology . Despite a positive rapid urease test, H . pylori was not isolated by culture or detected by histology and Gram smears . Based on these findings, a diagnosis of acute gastric mucosal lesions associated with H . heilmannii infection was established . This was successfully treated with a 2-week triple therapy consisting of lansoprazole, clarithromycin and metronidazole with persistent endoscopic and histological remission . This is a rare case of H . heilmannii-associated acute gastric mucosal lesions, diagnosed by morphology using touch cytology and histology . The patient might benefit from antimicrobial treatment employing the regimen effective for H . pylori.

Helicobacter, 2002 Oct, 7(5), 306 - 9
The relationship between consumption of antimicrobial agents and the prevalence of primary Helicobacter pylori resistance; Perez Aldana L et al.; BACKGROUND: Primary and acquired resistance to the antimicrobial agents is a primary reason for the failure of Helicobacter pylori eradication therapies . We assessed the primary antibiotic resistance rates of H . pylori to three different antibiotics and its relationship due to the annual antibiotic consumption in Japan during the period prior to approval of anti-H . pylori therapy in Japan . MATERIALS AND METHODS: Antibiotic susceptibility was tested using the agar dilution method for clarithromycin, amoxicillin and metronidazole . Isolates were considered resistant when the MIC value was > 8 mg/l for metronidazole, > 1 mg/l for clarithromycin and < 0.5 mg/l for amoxicillin . RESULTS: Helicobacter pylori isolates were obtained from 593 Japanese patients from 1995 to 2000 . Primary resistance of H . pylori to clarithromycin, metronidazole and amoxicillin was found in 11%, 9% and 0.3% strains, respectively . The proportion with clarithromycin resistance significantly increased from 7% in 1997-98 to 15.2% in 1999-2000 (p =.003) . During the same period the metronidazole resistance rate also increased from 6.6% in 1997-98 to 12% in 1999-2000 (p =.02) . The prevalence of clarithromycin and metronidazole was related to the annual consumption of these antimicrobial agents . CONCLUSION: Resistance rates for both clarithromycin and metronidazole appear to reflect the annual consumption of these agents . The high rate of clarithromycin resistance in Japan suggests that the effectiveness of clarithromycin-based therapies may be compromised in the near future.

Helicobacter, 2002 Oct, 7(5), 297 - 305
Emergence of clarithromycin-resistant Helicobacter pylori (CRHP) with a high prevalence in children compared with their parents; Taneike I et al.; BACKGROUND: Clarithromycin-resistant Helicobacter pylori (CRHP) is increasing worldwide . Clarithromycin resistance in H . pylori from familial members has not been investigated . MATERIALS AND METHODS: Biopsy specimens were taken from 13 families living in Tokyo, Yokohama, and Niigata between 1998 and 2001 . Drug resistance was tested with the replica plating method . The minimum inhibitory concentrations of antimicrobial agents for H . pylori strains were determined by the agar dilution method . Molecular analyses of H . pylori strains were performed by ribosomal RNA gene restriction pattern analysis . The DNA region, associated with clarithromycin resistance, was analyzed by PCR and sequencing . RESULTS: Helicobacter pylori strains isolated from a 5-year-old-son displayed clarithromycin resistance with a mutation (A --> G at position 2143) in the 23S ribosomal RNA, whereas H . pylori strains from his parents did not . DNA analyses revealed that the boy was infected with his father's strain . The boy had repeatedly developed otitis media and received clarithromycin since the age of 2 years . Studies on an additional 12 families demonstrated that clarithromycin resistance in the children's strains reached 42.9% and was significantly higher than those of H . pylori strains from their parents (0%) or from adult patients (11.1%) (p <.05) . CONCLUSIONS: The rate of clarithromycin resistance in H . pylori strains from Japanese children was extremely high, in contrast to those from their parents or adult patients . Prior history of clarithromycin usage in a child suggested development of clarithromycin resistance in resident H . pylori, which was originated from a parent.

Paediatr Drugs, 2002, 4(11), 729 - 35
Treatment of childhood eczema; Granlund H; Eczema in childhood is almost always atopic eczema, a common disease with huge impact on the quality of life of the child and family . Although atopic eczema constitutes part of the atopic syndrome, avoidance of allergens is never enough for disease control . Treatment of eczema in childhood has the same components as in adults . Emollients constitute the preventive background therapy in all stages of eczema, and topical corticosteroids are still the mainstay of treatment . Infectious exacerbation may require the use of a short course of topical or systemic antimicrobials . UV phototherapy should be considered as an adjunctive treatment to assist topical corticosteroids after an acute exacerbation of the disease . Cyclosporine can also be used in the treatment of childhood eczema in severe cases . Maternal allergen avoidance for disease prevention, oral antihistamines, Chinese herbs, dietary restriction in established atopic eczema, homeopathy, house-dust mite reduction, massage therapy, hypnotherapy, evening primrose oil, emollients, and topical coal tar are other temporarily used treatment modalities, without, however, firm evidence of efficacy from proper controlled trials . Calcineurin inhibitors constitute a new generation of drugs for both adult and childhood eczema already marketed in some countries . It is postulated that they will replace topical corticosteroids as first-line treatment of eczema.

Environ Toxicol Chem, 2002 Nov, 21(11), 2483 - 92
An ecological risk assessment for triclosan in lotic systems following discharge from wastewater treatment plants in the United States; Reiss R et al.; A modeling study was conducted to examine the distribution of concentrations of the antimicrobial triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) in rivers following discharge from wastewater treatment plants (WWTPs) . Most uses of triclosan are disposed of down residential drains and ultimately reach WWTPs . A modeling analysis was conducted to simulate the discharge of triclosan in WWTP effluents to rivers and calculate the expected concentrations based on characteristics of the reach where the discharge occurred, the estimated concentration of triclosan in the WWTP effluent, and the physicochemical properties of triclosan . A probabilistic exposure assessment was conducted based on data on the characteristics of U.S . reaches receiving wastewater discharges and the physicochemical characteristics of triclosan . A risk assessment was conducted by comparing the estimated concentrations with toxicity endpoint concentrations for species representative of key ecological groups . For fish and invertebrates, neither acute nor chronic risks are of concern, and no concerns exist for vascular aquatic plants . However, certain types of algae are the most sensitive species to triclosan by more than an order of magnitude than other algal or aquatic plant species . For these algae, the potential exists for some risk from triclosan exposure near the WWTP discharge location during low-flow-rate periods for some WWTPs with small dilutions . The risks downstream are lower because of dissipation of triclosan.

J Matern Fetal Neonatal Med, 2002 May, 11(5), 333 - 8
Osmolality of solutions, emulsions and drugs that may have a high osmolality: aspects of their use in neonatal care; Pereira-da-Silva L et al.; OBJECTIVE: Administration of some hypertonic substances to neonates has been associated with a variety of adverse effects . This study was conducted to determine the osmolality of intravenous drugs and solutions used in neonates receiving intensive care . METHODS: Osmolality was measured by freezing point depression . Vasoactive drugs, diuretics, anticonvulsants, antimicrobials, and glucose and electrolyte solutions were some of the substances analyzed . RESULTS: The osmolalities of 90 substances were measured; the respective intra-assay and interassay coefficients of variation were always less than 5% . A few drugs were found to be extremely hypertonic (> 8000 mOsm/kg), and most of them contain propylene glycol as vehicle (e.g . digoxin, phenytoin, diazepam and phenobarbital) . Other drugs, at the same concentration, evidenced a significant discrepancy of osmolality depending on the trademark . CONCLUSIONS: The finding of some extremely hypertonic drugs highlights the need for further investigation in order to study their potential adverse effects in neonates, as well as to evaluate any advantage in diluting, infusing slowly or even avoiding such substances . Given the fact that there exists a discrepancy in osmolalities in some drugs at the same concentration depending on the trademark, the more isotonic solutions should be the preferred choice for intravenous administration.

FEBS Lett, 2002 Oct 23, 530(1-3), 181 - 5
Five disulfide bridges stabilize a hevein-type antimicrobial peptide from the bark of spindle tree (Euonymus europaeus L.); Van den Bergh KP et al.; A small 45 amino acid residue antifungal polypeptide was isolated from the bark of spindle tree (Euonymus europaeus L.) . Though the primary structure of this so-called E . europaeus chitin-binding protein or Ee-CBP is highly similar to the hevein domain, it distinguishes itself from most previously identified hevein-type antimicrobial peptides (AMP) by the presence of two extra cysteine residues that form an extra disulfide bond . Due to these five disulfide bonds Ee-CBP is a remarkably stable protein . Agar diffusion and microtiterplate assays demonstrated that Ee-CBP is a potent antimicrobial protein . IC(50)-values as low as 1 microg/ml were observed for the fungus Botrytis cinerea . Comparative assays further demonstrated that Ee-CBP is a stronger inhibitor of fungal growth than Ac-AMP2 from Amaranthus caudatus seeds, which is considered one of the most potent antifungal hevein-type plant proteins.

Exp Eye Res, 2002 Oct, 75(4), 421 - 30
Molecular and cellular assessment of ginkgo biloba extract as a possible ophthalmic drug; Thiagarajan G et al.; We have investigated the biochemical and cell biological basis of the reported beneficiary effects of the leaf extracts of the plant Ginkgo biloba, which has been used as a possible ophthalmic drug . The antioxidant, antimicrobial, anti-apoptotic and cytoprotective properties of the standardized extract called EGb761 were assayed . Chemical stresses were induced in cells using alloxan or dexamethasone, and the effect of EGb761 on them was studied using the MTT and TUNEL assays . Its ability to modulate the activities of some antioxidant enzymes was tested in vitro . In addition, cataract was induced in rats through selenite injection, and the effect of EGb761 administration on the progression of cataract was studied using slit lamp examination . Ginkgo biloba was found to be an excellent antioxidant . It readily scavenges reactive oxygen and nitrogen radicals and inhibits oxidative modifications that occur to proteins in vitro . It enters intact cells and protects them from alloxan-mediated and light-mediated stress, and the nuclear DNA from single strand breaks . It also effectively inhibits chemically induced apoptosis . It does not modulate the activities of endogenous antioxidant enzymes, nor does it have any significant antimicrobial activity . Unlike some other plant extracts, it is not phototoxic . In experiments wherein selenite cataract was induced in laboratory rats, treatment with the extract significantly retards the progression of lens opacification in vivo . Ginkgo biloba's inherent antioxidant, antiapoptotic and cytoprotective action and potential anticataract ability appear to be some of the factors responsible for its beneficial effects.

Expert Opin Pharmacother, 2002 Oct, 3(10), 1461 - 70
Treatment of Chlamydia pneumoniae infection and chronic obstructive pulmonary disease; Karnak D et al.; Chronic obstructive lung disease (COPD) is a general term for chronic, irreversible lung disease that combines qualities of emphysema and chronic bronchitis . The standard definition of chronic bronchitis is a productive cough for three months per year (for at least two consecutive years) without an underlying aetiology . Acute exacerbation of chronic bronchitis (AECB) represents a common complaint that leads patients to seek medical attention . COPD and AECB are directly responsible for the overuse of antibiotics in the developed world . Fifty per cent of exacerbations have either viral or non-infectious origin . For this reason, antibiotic use remains controversial . Among other bacteria, Chlamydia pneumoniae is responsible for 4 - 16% of AECB in hospitalised or out-patients, although among smokers and people using steroids, the incidence is 34% . C . pneumoniae may either be the sole causative agent or a co-agent in AECB . This paper reviews the management of COPD/AECB with respect to antibiotic use . Diagnosis and antimicrobial therapy relevant to Chlamydia in the management of AECB are also evaluated in this review.

Rinsho Byori, 2002 Sep, 50(9), 860 - 8
{Detection of drug resistant bacteria and correspondence of microbiological laboratory to clinical physicians}; Komori T; The world is now being faced with the battle for antimicrobial resistant organisms(ARO), such as MRSA, PRSP, ESBL producing GNR, MDRP and VRSA . These AROs are causing hospital-acquired infections(HAI) by the way of person-to-person transmission . The role of microbiological laboratories in hospitals is quite important in controlling HAI . Firstly, accurate detection of AROs is essential . They have to be proficient in both isolation and detection of AROs . Secondly, they have to return the results rapidly for not only clinicians but infection control team(ICT) to prevent more spread of HAI if an isolated organism is ARO . Thirdly, they have to report the statistical data about isolated organisms for ICT in each hospital . AROs can be isolated by three major methods, detection of responsible resistant genes or proteins and antimicrobial susceptibility tests . Most laboratories isolate AROs, using one or two of these methods . They should be prepared for and follow the most current criteria of AROs by Japanese original standard, or presented from NCCLS . Microbiological laboratories should also play a role in both hospital epidemiology and appropriate antimicrobial use by providing useful information, annual or periodical reports of antimicrobial susceptibility for isolated organisms which are relevant in their hospital . The microbiological laboratory which have good skills in detecting AROs, analyzing epidemiological data and communicating with all hospital workers, is now required from ICT in controlling HAI.

Fitoterapia, 2002 Oct, 73(6), 540 - 3
Antimicrobial activity and cytotoxicity of Carthamus lanatus; Taskova R et al.; Total dichloromethane, methanol and water extracts, their fractions as well as volatiles of Carthamus lanatus aerial parts were phytochemically screened and evaluated for antibacterial, antifungal and cytotoxic activity . The H(2)O/MeOH fraction of the CH(2)Cl(2) extract exhibited noticeable antibacterial activity . The same fraction and the volatiles showed significant cytotoxic activity .

Fitoterapia, 2002 Oct, 73(6), 523 - 5
Antimicrobial activity of Hymenodictyon parvifolium; Kariba RM; Methanol extract of the stem bark of Hymenodictyon parvifolium was tested for its antifungal and antibacterial activity . The extract was found to have inhibitory effect against all the pathogens tested .

Fitoterapia, 2002 Oct, 73(6), 514 - 6
Antimicrobial activity of Solidago virgaurea L . from in vitro cultures; Thiem B et al.; The antimicrobial activity of ethanolic and methanolic extracts of Solidago virgaurea herb from micropropagated plants and callus tissue was evaluated .

Fitoterapia, 2002 Oct, 73(6), 511 - 3
Composition and antimicrobial activity of the essential oil of Hypericum coris; Schwob I et al.; The volatile fraction of Hypericum coris aerial parts, consisting mainly of alpha-curcumene was screened for activity against five microbial strains . The maximum activity was against Saccharomyces cerevisiae .

Int J Antimicrob Agents, 2002 Sep, 20(3), 214 - 9
Antibacterial, antifungal and cytotoxic activities of extracts from fish epidermis and epidermal mucus; Hellio C et al.; Annual discards from the world fisheries are estimated to be approximately 20 million metric tonnes (25%) per year . The main objective of this work is to increase the utilisation of by-products (notably skin) from fish species in order to isolate new biologically active compounds . This study presents the results of a screening program for antifungal, antibacterial and cytotoxic activities in epidermal mucus and epidermis extracts of thirteen fish species that are commonly caught in North Atlantic waters and generate an important amount of fish waste . Antimicrobial assays used five Gram-positive bacteria five Gram-negative bacteria and five fungi . Of the 78 extracts tested, 15 showed antibacterial and/or antifungal activities . None of the aqueous fractions were active . One third of the active extracts were ethanolic fractions and three fourth of extracts were dichloromethane fractions . One third of the active fractions were of epidermal origin and the remaining came from mucus fractions . The high levels of inhibitory activity and no apparent toxicity against mouse fibroblasts of extracts of Pollachius virens (CH(3)CH(2)OH/epidermis), Labrus bergylta (CH(2)Cl(2)/mucus), Platichthys flesus (CH(3)CH(2)OH/mucus), Solea solea (CH(2)Cl(2)/mucus) and Scophtalamus rhombus (CH(2)Cl(2)/mucus) suggest they may have potential as novel active therapeutic agents .

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