Clin Infect Dis, 2005 Jan 15, 40(2), 239 - 45 Epub 2004 Dec 20. A European organization for research and treatment of cancer-international antimicrobial therapy group study of secondary infections in febrile, neutropenic patients with cancer; Akova M et al.; BACKGROUND: Neutropenic patients with cancer may develop several episodes of fever and infection during chemotherapy-induced myeloaplasia . METHODS: To identify risk factors for secondary infectious episodes among patients who responded to initial antibiotic therapy, we retrospectively analyzed 2 consecutive, prospective, randomized clinical trials performed by the International Antimicrobial Therapy Group of the European Organization for Research and Treatment of Cancer during 1991-1994 . RESULTS: Of 1720 patients with their first episode of febrile neutropenia, 836 responded to the initial antibiotic regimen and were therefore suitable for our analysis . A secondary infection was observed in 129 (15%) of 836 patients that occurred at a median of 10 days (range, 1-28 days) after the onset of the primary febrile episode . Factors at both baseline and day 4 were analyzed . Age of >16 years (odds ratio {OR}, 3.46; P<.001), acute leukemia in first induction (OR, 3.17; P<.001), presence of intravenous line (OR, 1.88; P=.04), severe neutropenia (defined as an absolute granulocyte count of <100 cells/mm(3)) on day 4 (OR, 2.72; P<.001), and type of documentation of the primary episode (i.e., microbiologically documented cause or unexplained fever; OR, 2.56; P=.001) were found to be risk factors for secondary infection . The risk of death was higher among patients who developed a secondary infectious episode than among those who did not (5.4% vs . 1.4%; P<.01) . CONCLUSIONS: The clinical parameters described above may help to identify neutropenic patients at risk of developing secondary infection. Am J Gastroenterol, 2005 Jan, 100(1), 201 - 6 The emerging role of the liver in iron metabolism; Sharma N et al.; Iron is essential in health and well-being and its dysregulation is a common theme in disease . Recent advances in our understanding of the molecular biology underlying hemochromatosis and anemia has provided insight into the complex mechanisms implicated in iron metabolism . The proximal small bowel is the major site of iron absorption and, it is becoming increasingly clear that the regulation of this process involves the liver and, in particular, the hepatic antimicrobial peptide hepcidin . A number of studies have shown hepcidin to have an inhibitory function at the level of small bowel iron absorption, although its exact site of action remains to be elucidated . Clearly, identifying the target of hepcidin is of importance and is likely to lead to the development of therapeutic agents in the treatment of iron disorders. Bull World Health Organ, 2004 Dec, 82(12), 928 - 934 Epub 2005 Jan 05. The antimicrobial resistance containment and surveillance approach - a public health tool; Simonsen GS et al.; Antimicrobial drug resistance (AMR) is widely recognized as a global public health threat because it endangers the effectiveness of treatment of infectious diseases . In 2001 WHO issued the Global Strategy for Containment of Antimicrobial Resistance, but it has proved difficult to translate the recommendations of the Global Strategy into effective public health actions . The purpose of the Antimicrobial Resistance Containment and Surveillance (ARCS) approach is to facilitate the formulation of public health programmes and the mobilization of human and financial resources for the containment of AMR . The ARCS approach highlights the fundamental link between rational drug use and containment of AMR . Clinical management of human and animal infections should be improved through better disease control and prevention, high quality diagnostic testing, appropriate treatment regimens and consumer health education . At the same time, systems for supplying antimicrobial drugs should include appropriate regulations, lists of essential drugs, and functional mechanisms for the approval and delivery of drugs . Containment of AMR is defined in the ARCS approach as the continuous application of this package of core interventions . Surveillance of the extent and trends of antimicrobial resistance as well as the supply, selection and use of antimicrobial drugs should be established to monitor the process and outcome of containment of AMR . The ARCS approach is represented in the ARCS diagram (<A HREF="/img/revistas/bwho/v82n12/fig_2_9100.gif">Fig . 2</A>) which provides a simplified, but comprehensive illustration of the complex problem of containment and monitoring of AMR. Curr Opin Immunol, 2005 Feb, 17(1), 88 - 94 CD1 assembly and the formation of CD1-antigen complexes; Hava DL et al.; The CD1 antigen presentation system presents lipid antigens to effector T cells, which have diverse roles in antimicrobial responses, antitumor immunity and in regulating the balance between tolerance and autoimmunity . The trafficking of CD1 molecules and lipid antigens facilitates their intersection and binding in specific intracellular compartments . Recent studies have now identified unexpected accessory molecules that are critical to CD1 assembly and lipid loading . The atomic structures of CD1-antigen complexes have defined both the orientation of polar headgroups between the alpha1 and alpha2 helices of CD1 and the manner in which distinct CD1 isoforms bind a range of lipids that have different lengths and numbers of hydrocarbon chains. Curr Opin Immunol, 2005 Feb, 17(1), 11 - 7 Sensing and signaling during infection in Drosophila; Royet J et al.; Most of the progress in dissecting the Drosophila antimicrobial response over the past decade has centered around intracellular signaling pathways in immune response tissues and expression of genes encoding antimicrobial peptide genes . The past few years, however, have witnessed significant advances in our understanding of the recognition of microbial invaders and subsequent activation of signaling cascades . In particular, the roles of peptidoglycan recognition proteins, which have known homologues in mammals, have been recognized and examined at the structural and functional levels. J Control Release, 2005 Jan 20, 102(1), 223 - 33 Incorporation of low molecular weight biocides into polystyrene-divinyl benzene beads with controlled release characteristics; Iconomopoulou SM et al.; Triclosan and phosphonium salt biocides have been separately incorporated into polystyrene-divinylbenzene (PS-DVB) beads by suspension polymerization . Ultraviolet (UV) absorption measurements have been used to monitor the release of these low molecular weight biocides out of the PS-DVB beads immersed in water-ethanol mixtures and in physiological saline . The release of the biocide agents is strongly dependent on either the DVB or/and the antimicrobial composition ratio in the beads . An increase of biocide incorporation in the PS/DVB beads was accompanied by a corresponding enhancement of its concentration in liquid mixtures . On the contrary, higher cross-linking densities hindered the biocide migration out of the beads by diminishing its release rate into either the aqueous ethanol solutions or the natural serum . Moreover, Fourier transform Raman (FT-Raman) spectra and Attenuated Total Reflectance Infrared (ATR-FTIR) measurements of the PS-DVB-Triclosan and PS-DVB-phosphonium salt beads, before and after their immersion in water-ethanol solutions, gave a similar qualitative evidence of the biocide release. FEMS Microbiol Rev, 2005 Jan, 29(1), 99 - 117 Some lessons from Rickettsia genomics; Renesto P et al.; Sequencing of the Rickettsia conorii genome and its comparison with its closest sequenced pathogenic relative, i.e., Rickettsia prowazekii, provided powerful insights into the evolution of these microbial pathogens . However, advances in our knowledge of rickettsial diseases are still hindered by the difficulty of working with strict intracellular bacteria and their hosts . Information gained from comparing the genomes of closely related organisms will shed new light on proteins susceptible to be targeted in specific diagnostic assays, by new antimicrobial drugs, and that could be employed in the generation of future rickettsial vaccines . In this review we present a detailed comparison of the metabolic pathways of these bacteria as well as the polymorphisms of their membrane proteins, transporters and putative virulence factors . Environmental adaptation of Rickettsia is also discussed. Peptides, 2005 Mar, 26(3), 369 - 75 Deletion of two C-terminal Gln residues of 12-26-residue fragment of melittin improves its antimicrobial activity; Sun X et al.; In our previous paper it was shown that the two C-terminal Gln residues of a C-terminal 15-residue fragment, Mel(12-26) (GLPALISWIKRKRQQ-NH(2)), of melittin and a series of individual substituted analogues might not involved in the interaction with bacterial membranes . In this paper, peptides with one and two Gln residues deletion, respectively, Mel(12-25) and Mel(12-24), were synthesized and characterized . Both of the deletion peptides showed higher antimicrobial activities than the parent peptide, Mel(12-26) . If both of the Gln residues of Mel(12-26) were respectively replaced by a hydrophilic amino acid Gly, the antimicrobial activity increased slightly . If the Gln residue of Mel(12-25) was replaced by a hydrophobic amino acid Leu, the antimicrobial activity changed little, although the substituted peptide possessed much higher hydrophobicity and higher alpha-helical conformation percentage in 1,1,1,3,3,3-hexafluoro-2-propanol/water determined by circular dichroism spectroscopy (CD) than the parent peptide . These results indicated that the two C-terminal residues might be indeed not involved in the binding to bacterial membranes . The antimicrobial activity increasing with the residue deletion may be caused by the decrease of the translational and rotational entropic cost of the binding of the peptides to bacterial membranes because of the lower molecular weights of the deletion peptides. Biochim Biophys Acta, 2005 Jan 18, 1721(1-3), 73 - 80 Epub 2004 Nov 06. cDNA microarray analysis of lactoferrin expression in non-neoplastic human hepatocyte PH5CH8 cells; Tamura T et al.; Lactoferrin (LF), a milk protein belonging to the iron transporter transferrin family, is known as a primary defense protein against pathogenic microorganisms . Previously, we found that bovine and human LFs prevented hepatitis C virus infection in cultured human hepatocytes by a direct interaction with the virus . Since LF is proposed to have transcriptional regulatory activity in addition to its antimicrobial function, we sought to identify the target genes that these two types of LF have in common . To this end, we were the first to perform microarray analysis (9970 genes) using human hepatocytes that expressed bovine or human LF by retrovirus-mediated gene transfer . In the results, LF could give a variety of expression profiles in the human hepatocytes, and showed that 9 and 19 genes were commonly up-regulated (more than 2.0-fold) and down-regulated (less than 0.50-fold), respectively, in both bovine and human LF-expressing cells compared with control cells . Among these genes, we found that gamma-aminobutyric acid (GABA)-B receptor 2 was transcriptionally down-regulated by bovine and human LFs, but not by human transferrin . Furthermore, we obtained the suggestive result that LF may modulate the level of intracellular cAMP . This modulation is one of the cellular responses that the GABA-B receptor modifies . This is the first report of microarray analysis applied to search inclusively for the target genes of LF. Nippon Geka Gakkai Zasshi, 2004 Dec, 105(12), 734 - 6 {Pulmonary infection in immunocompromised hosts}; Suzuki T et al.; While typical pulmonary infections can be cured with antimicrobial agents, three types require surgical lung resection: those in immunocompromised patients; those with acquired resistance to medication; and those caused by microorganisms against which there are no effective drugs . We discuss these three types from the viewpoint of physicians . With the development of chemotherapy for malignant disease, patients with leukemia can be cured with bone marrow transplantation . During the leukopenia accompanying chemotherapy, Aspergillus sp . can infect the lungs . Aspergillus infections are resistant to antimicrobial agents, and thus surgical resection is necessary . Aspergillus infections may occur in previous sites of pulmonary tuberculosis lesions after the tuberculosis is cured producing massive hemoptysis . In this case, surgical resection is also needed . When patients who are immunocompromised due to various underlying diseases become infected with multidrug-resistant tuberculosis, they require surgical resection . Finally, when lesions of nontubercular mycobacterial infection are found, these patients also require surgical lung resection. J Investig Med, 2004 Nov, 52(7), 470 - 4 Clinical experience with drotrecogin alfa in treating gram-positive and -negative pathogens in patients with severe sepsis; Cone LA et al.; BACKGROUND: Newer concepts in the management of severe sepsis and, in particular, in the understanding of the relationship between proinflammatory and procoagulant activities during severe infection have led to the introduction of activated protein C (drotrecogin) into the therapeutic program . The combination of effective antimicrobial therapy, aggressive supportive care, and efforts to antagonize procoagulants and inhibitors of fibrinolysis was used in this study . METHODS: We treated 12 patients with severe sepsis using this combination of antimicrobial agents and drotrecogin . All patients presented with hypotension and organ failure and some with multiple organ failure . Infected patients were separated into those with gram-positive and those with gram-negative infections . RESULTS: In contrast to an expected mortality rate of nearly 40% in this group of patients, only 2 (9%) expired . Both deaths were due to infection by gram-negative organisms in patients with complicated abdominal infections and concurrent cancer . All patients with gram-positive organisms survived . CONCLUSION: Those patients with infections caused by gram-positive organisms seemed to have a better prognosis than those with gram-negative infections, perhaps because their illnesses are less complicated by local disease . Although our study is small, it suggests that activated protein C will have a significant beneficial effect on the future treatment of severe sepsis and can reduce the mortality rate significantly . Further improvement in survival rates will require more effective treatment of local disease and associated noninfectious ailments. J Clin Invest . 2005 Jan 13; {Epub ahead of print} Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance; Marriott HM et al.; Macrophages are critical effectors of bacterial clearance and must retain viability, despite exposure to toxic bacterial products, until key antimicrobial functions are performed . Subsequently, host-mediated macrophage apoptosis aids resolution of infection . The ability of macrophages to make this transition from resistance to susceptibility to apoptosis is important for effective host innate immune responses . We investigated the role of Mcl-1, an essential regulator of macrophage lifespan, in this switch from viability to apoptosis, using the model of pneumococcal-associated macrophage apoptosis . Upon exposure to pneumococci, macrophages initially upregulate Mcl-1 protein and maintain viability for up to 14 hours . Subsequently, macrophages reduce expression of full-length Mcl-1 and upregulate a 34-kDa isoform of Mcl-1 corresponding to a novel BH3-only splice variant, Mcl-1(Exon-1) . Change in expression of Mcl-1 protein is associated with mitochondrial membrane permeabilization, which is characterized by loss of mitochondrial inner transmembrane potential and translocation of cytochrome c and apoptosis-inducing factor . Following pneumococcal infection, macrophages expressing full-length human Mcl-1 as a transgene exhibit a delay in apoptosis and in bacterial killing . Mcl-1 transgenic mice clear pneumococci from the lung less efficiently than nontransgenic mice . Dynamic changes in Mcl-1 expression determine macrophage viability as well as antibacterial host defense. Toxicol In Vitro, 2005 Mar, 19(2), 199 - 206 Influences of ozone exposure upon macrophage responsivity to N-formyl-methionyl-leucyl-phenylalanine: mobility and metabolic changes; Klestadt D et al.; Alveolar macrophages represent one of the first lines of cell defence in the lungs . They employ several mechanisms, including phagocytosis and secretion of reactive oxygen and nitrogen species . fMLP, a formylated peptide of bacterial origin, is a potent inducer of phagocyte chemotaxis and is also involved in generating antimicrobial agents such as nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) . In this study we analysed the in vitro effects of fMLP on the mobility of the THP-1 cell line, which served as a model for alveolar macrophages . Cell mobility and cytotoxicity were also analysed after pre-exposures to an atmosphere polluted with ozone (0.03-0.5ppm) followed by a fMLP treatment . Finally, the secreted molecules (H(2)O(2) and NO) were measured after ozone exposures ranging from 5 to 30min and fMLP action . Activation by fMLP alone induced cell movement, whereas pre-exposure to the ozone concentrations decreased it . Addition of fMLP had different effects on cytotoxicity, mobility and metabolite secretion by the cells: (1) cytotoxicity increased depending on ozone concentrations and exposure times; (2) during the first 5min and for all ozone concentrations, an average decrease of 50% of activated cell mobility was observed; (3) H(2)O(2) was increased, even in combination with ozone; (4) NO was detected at 731nM, a result that was not affected by ozone pre-exposure. Biochem Biophys Res Commun, 2005 Feb 18, 327(3), 945 - 51 Maximins S, a novel group of antimicrobial peptides from toad Bombina maxima; Wang T et al.; Amphibian skin secretions are rich in antimicrobial peptides acting as important components of innate defense system against invading microorganisms . A novel type of peptide, designated as maximin S, was deduced by random sequencing of 793 clones from a constructed Bombina maxima skin cDNA library . The putative primary structures of maximin S peptides can be grouped into five species, in which maximin S1 has 14 amino acid residues and the rest of maximin S peptides (S2-S5) all have 18 amino acid residues . Unlike most of the amphibian antimicrobial peptides so far identified, the newly characterized four maximin S precursors are composed of maximin S1 and different combinations of tandem repeated maximin S2-S5 linked by internal peptides . Except maximin S1, the predicted secondary structures of maximin S2-S5 show a similar amphipathic alpha-helical structure . MALDI-TOF mass spectrometry analysis of partially isolated skin secretions of the toad indicates that most of the deduced maximin S peptides are expressed . Two deduced maximin S peptides (S1, S4) were synthesized and their antimicrobial activities were tested . Maximin S4 only had an antibiotic activity against mycoplasma and had no antibacterial or antifungal activity toward tested strains . Maximin S1 had no activity under the same conditions. Anal Biochem, 2005 Feb 1, 337(1), 149 - 53 Studies on the membrane interactions of the cyclotides kalata B1 and kalata B6 on model membrane systems by surface plasmon resonance; Kamimori H et al.; In this study we have demonstrated the interactions of kalata B1 and its naturally occurring analogue kalata B6 with five model lipid membranes and have analyzed the binding kinetics using surface plasmon resonance . Two kalata peptides showed a higher affinity for the phosphatidylethanolamine-containing membranes, indicating that the peptides would bind selectively to bacterial membranes . Also we have optimized the procedure for the immobilization of five liposome mixtures and have shown that the procedure provides reproducible levels of immobilized liposomes and could be used to screen the selective binding of putative antimicrobial peptides to model mammalian or microbial phospholipid membranes. J Fluoresc, 2004 Nov, 14(6), 705 - 10 The interaction between levofloxacine hydrochloride and DNA mediated by Cu2+; Song G et al.; Levofloxacin (LEV) is a fluoroquinolone antimicrobial agent . LEV also inhibits DNA synthesis and is bactericidal . The mechanisms of the interaction among LEV, DNA and Cu2+ are studied by fluorescence method . In the paper, the results show that LEV and Cu2+ can form binary complex, and also LEV and DNA can form complex mediated by Cu2+ . The composition of the complex is determined . The affects to the reaction are also found. Protein J, 2004 Nov, 23(8), 501 - 8 Ocellatins: new antimicrobial peptides from the skin secretion of the South American frog Leptodactylus ocellatus (Anura: Leptodactylidae); Nascimento AC et al.; The emergence, in recent years, of microbial resistance to commonly used antibiotics has aroused a search for new naturally occurring bactericidal and fungicidal agents that may have clinical utility . In the present study, three new antimicrobial peptides were purified from the electrical-stimulated skin secretion of the South American frog Leptodactylus ocellatus by reversed-phase chromatographic procedures . Ocellatin 1 (1GVVDILKGAGKDLLAHLVGKISEKV25-CONH2), ocellatin 2 (1GVLDIFKDAAKQILAHAAEKQI25-CONH2) and ocellatin 3 (1GVLDILKNAAKNILAHAAEQI21-CONH2) are structurally related peptides . These peptides present hemolytic activity against human erythrocytes and are also active against Escherichia coli . Ocellatins exhibit significant sequence similarity to other amphibian antimicrobial peptides, mainly to brevinin 2ED from Rana esculenta. J Crit Care, 2004 Dec, 19(4), 271 - 8 Computerized physician order entry in the critical care and general inpatient setting: A narrative review; Rothschild J; Computerized physician order entry (CPOE) is an increasingly used technologic tool for entering clinician orders, especially for medications and laboratory and diagnostic tests . Studies in hospitalized patients, including critically ill patients, have demonstrated that CPOE, especially with decision support, improves several outcomes . These improved outcomes include clinical measures such as reductions in serious medication errors and enhanced antimicrobial management of critically ill patients resulting in reduced length of stay . Additionally, several process outcomes have improved with CPOE such as increased compliance with evidence-based practices, reductions in unnecessary laboratory tests and cost savings in pharmacotherapeutics . Future studies are needed to demonstrate the benefits of more patient specific decision support interventions and the seamless integration of CPOE into a wireless, computerized medication administration system. Appl Microbiol Biotechnol . 2005 Jan 13; {Epub ahead of print} A novel actinomycete strain de-replication approach based on the diversity of polyketide synthase and nonribosomal peptide synthetase biosynthetic pathways; Ayuso A et al.; The actinomycetes traditionally represent one of the most important sources for the discovery of new metabolites with biological activity; and many of these are described as being produced by polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS) . We present a strain characterization system based on the metabolic potential of microbial strains by targeting these biosynthetic genes . After an initial evaluation of the existing bias derived from the PCR detection in a well defined biosynthetic systems, we developed a new fingerprinting approach based on the restriction analysis of these PKS and NRPS amplified sequences . This method was applied to study the distribution of PKS and NRPS biosynthetic systems in a collection of wild-type actinomycetes isolated from tropical soil samples that were evaluated for the production of antimicrobial activities . We discuss the application of this tool as an alternative characterization approach for actinomycetes and we comment on the relationship observed between the presence of PKS-I, PKS-II and NRPS sequences and the antimicrobial activities observed in some of the microbial groups tested. J Biol Chem . 2005 Jan 12; {Epub ahead of print} Transcriptional responses of Escherichia coli to S-nitrosoglutathione under defined chemostat conditions reveal major changes in methionine biosynthesis; Flatley J et al.; Nitric oxide and nitrosating agents exert powerful antimicrobial effects and are central to host defence and signal transduction . Nitric oxide and S-nitrosothiols can be metabolised by bacteria but only a few enzymes have been shown to be important in responses to such stresses . Glycerol-limited chemostat cultures in defined medium of Escherichia coli MG1655 were used to provide bacteria in defined physiological states before applying nitrosative stress by addition of S-nitrosoglutathione (GSNO) . Exposure to 200 mM GSNO for 5 min was sufficient to elicit an adaptive response as judged by the development of NO-insensitive respiration . Transcriptome profiling experiments were used to investigate the transcriptional basis of the observed adaptation to the presence of GSNO . In aerobic cultures, only seventeen genes were significantly up-regulated, including genes known to be involved in NO tolerance, particularly hmp (encoding the NO-consuming flavohemoglobin Hmp) and norV (encoding flavorubredoxin) . Significantly, none of the up-regulated genes were members of the Fur regulon . Six genes involved in methionine biosynthesis or regulation were significantly up-regulated; metN, metI and metR were shown to be important for GSNO tolerance since mutants in these genes exhibited GSNO growth sensitivity . Furthermore, exogenous methionine abrogated the toxicity of GSNO supporting the hypothesis that GSNO nitrosates homocysteine, thereby withdrawing this intermediate from the methionine biosynthetic pathway . Anaerobically, ten genes showed significant up-regulation, of which norV, hcp, metR and metB were also up-regulated aerobically . The data presented here reveal new genes important for nitrosative stress tolerance and demonstrate that methionine biosynthesis is a casualty of nitrosative stress. Compend Contin Educ Dent, 2004 Jul, 25(7 Suppl 1), 46 - 53 Effectiveness of a triclosan/copolymer dentifrice on microbiological and inflammatory parameters; Xu T et al.; According to the US Surgeon General's report, "Oral Health in America," published in 2000, most adults in the United States show some degree of periodontal pathology, with severe periodontal diseases affecting about 14% of middle-aged adults . Periodontal diseases are polymicrobial-induced inflammatory diseases, and they vary from mild gingival inflammation to severe deterioration of the periodontium, ie, loss of periodontal supportive tissues and, ultimately, tooth loss . New evidence shows that periodontal diseases may impact systemic health . For this reason, the maintenance of a healthy mouth is becoming increasingly important for the overall health of the body . This article summarizes laboratory research conducted during the development of a novel, multibenefit, oral-care technology based on triclosan--a broad-spectrum antibacterial agent--and a polyvinylmethylether/maleic acid copolymer . This unique combination of agents is found in Colgate Total, a clinically proven efficacious dentifrice for control of dental plaque and gingivitis . Data are presented that demonstrate the unique antibacterial properties of this dentifrice: (1) a broad-spectrum antimicrobial profile; (2) the long-lasting retention of triclosan on hydroxyapatite and epithelial cells; and (3) molecular evidence of antibacterial activity against specific pathogens in clinical dental plaque . In addition, data are presented that demonstrate the anti-inflammatory effects of triclosan on specific cytokines, the interruption of inflammatory pathways, and the inhibition of bone resorption . Overall, these data support the multibenefit clinical effects of Colgate Total and suggest a plurality of mechanisms of action. Br J Pharmacol, 2005 Jan, 144(1), 80 - 7 Pharmacodynamics and pharmacokinetics of SQ109, a new diamine-based antitubercular drug; Jia L et al.; SQ109 is a novel {1,2}-diamine-based ethambutol (EMB) analog developed from high-throughput combinatorial screening . The present study aimed at characterizing its pharmacodynamics and pharmacokinetics.The antimicrobial activity of SQ109 was confirmed in vitro (Mycobacterium tuberculosis-infected murine macrophages) and in vivo (M . tuberculosis-infected C57BL/6 mice) and compared to isoniazid (INH) and EMB . SQ109 showed potency and efficacy in inhibiting intracellular M . tuberculosis that was similar to INH, but superior to EMB . In vivo oral administration of SQ109 (0.1-25 mg kg(-1) day(-1)) to the mice for 28 days resulted in dose-dependent reductions of mycobacterial load in both spleen and lung comparable to that of EMB administered at 100 mg kg(-1) day(-1), but was less potent than INH at 25 mg kg(-1) day(-1) . Monitoring of SQ109 levels in mouse tissues on days 1, 14 and 28 following 28-day oral administration (10 mg kg(-1) day(-1)) revealed that lungs and spleen contained the highest concentration of SQ109, at least 10 times above its MIC.Pharmacokinetic profiles of SQ109 in mice following a single administration showed its C(max) as 1038 (intravenous (i.v.)) and 135 ng ml(-1) (p.o.), with an oral T(max) of 0.31 h . The elimination t(1/2) of SQ109 was 3.5 (i.v.) and 5.2 h (p.o.) . The oral bioavailability was 4% . However, SQ109 displayed a large volume of distribution into various tissues . The highest concentration of SQ109 was present in lung (>MIC), which was at least 120-fold (p.o.) and 180-fold (i.v.) higher than that in plasma . The next ranked tissues were spleen and kidney . SQ109 levels in most tissues after a single administration were significantly higher than that in blood . High tissue concentrations of SQ109 persisted for the observation period (10 h).This study demonstrated that SQ109 displays promising in vitro and in vivo antitubercular activity with favorable targeted tissue distribution properties.British Journal of Pharmacology (2005) 144, 80-87 . doi:10.1038/sj.bjp.0705984. Water Res, 2005 Jan-Feb, 39(2-3), 331 - 9 Epub 2004 Nov 24. Modeling antimicrobial contaminant removal in slow sand filtration; Rooklidge SJ et al.; Slow sand filters are used in rural regions where source water may be subjected to antimicrobial contaminant loads from waste discharges and diffuse pollution . A numerical model (LETA) was derived to calculate aqueous antimicrobial concentrations through time and depth of a slow sand filter and estimate accumulating contaminant mass in the schmutzdecke . Input parameters include water quality variables easily quantified by water system personnel and published adsorption, partitioning, and degradation coefficients . Simulation results for the tetracycline, quinolone, and macrolide classes of antimicrobials suggested greater than 3-log removal from 1mug/L influent concentrations within the top 40cm of the sand column, with schmutzdecke antimicrobial concentrations comparable to other land-applied waste biosolids . A 60-day challenge experiment injecting 1mug/L tylosin to a pilot slow sand filter showed an average 0.1mg/kg of the antimicrobial remaining in the schmutzdecke layer normally removed during filter maintenance, and this value was the same order of magnitude as the sorbed concentration predicted by the LETA model. Lett Appl Microbiol, 2005, 40(2), 138 - 45 Characterization of minimal bacteriocin operon from Prevotella nigrescens ATCC 25261; Kaewsrichan J et al.; Abstract j . kaewsrichan, c.w.i . douglas and r . teanpaisan . 2004.Aims: To characterize a minimal bacteriocin operon of Prevotella nigrescens ATCC 25261 . Methods and Results: A genomic DNA library of Pr . nigrescens ATCC 25261 was constructed and screened for bacteriocin production by an agar overlay assay . Sequence analysis of the bacteriocin-producing recombinant plasmid, pGP2, has shown that the insert DNA consists of 4868 base pairs, termed nig locus . There is a cluster of four genes within the nig locus, respectively designated nigA, B, C and D . Deleting 160 nucleotides at the 3'-end of nigAB resulted in loss of bacteriocin production, indicating that nigAB may belong to a bacteriocin operon . nigA is thought to be the bacteriocin gene, while nigB may encode an immunity protein . Escherichia coli containing pGP2 expressed the bacteriocin, which is similar in size, antimicrobial activity, and biochemical properties to that purified from Pr . nigrescens ATCC 25261 . Conclusion: nig Locus is a chromosomal fragment of Pr . nigrescens ATCC 25261, consisting of 4868 base pairs, and has been proved to be important for bacteriocin production . Significance and Impact of the Study: This is the first report of the successful cloning and expression of the bacteriocin from Pr . nigrescens ATCC 25261 into E . coli . This will facilitate the construction of bacteriocin analogues and permit investigation of their structure/function relationships. Lett Appl Microbiol, 2005, 40(2), 106 - 10 Development of a bioactive packaging cellophane using Nisaplin as biopreservative agent; Guerra NP et al.; Abstract n.p . guerra, c.l . macias, a.t . agrasar and l.p . castro . 2004.Aims: Production of a nisin-containing cellophane-based coating to be used in the packaging of chopped meat . Methods and Results: The adsorption of nisin to cellophane 'P' type surface was studied at 8, 25, 40 and 60 degrees C using different concentrations of nisin . Then, the antimicrobial activity of adsorbed nisin to cellophane surface was determined in fresh veal meat for effectiveness in reducing the total aerobic bacteria . The adsorption of nisin to cellophane was higher at 8 degrees C . The developed bioactive cellophane reduced significantly the growth of the total aerobic bacteria (by ca 1.5 log units) through 12 days of storage at 4 degrees C . Conclusions: Bioactive cellophane packaging could be used for controlling the microbial growth in chopped meat . Significance and Impact of the Study: Nisin-adsorbed bioactive cellophane would result in an extension of the shelf life of chopped meat under refrigeration temperatures. Planta Med, 2004 Dec, 70(12), 1144 - 1149 Alencar NM, Figueiredo IS, Vale MR, Bitencurt FS, Oliveira JS, Ribeiro RA, Ramos MV. Latex from Calotropis procera is widely used in folk medicine as a rich source of biologically active compounds capable of promoting diverse benefits such as control of dermal fungal infections, antimicrobial activities and pain relief among other useful properties . The aim of this work was to characterize the anti-inflammatory effect of a non-dialysable protein fraction recovered from the rubber-free latex using three different experimental models when administrated intravenously . In vivo neutrophil migration induced by carrageenin (500 mug) was severely inhibited by doses of latex proteins reaching maximum inhibition (80 %) at 100 mg/kg . Paw edema exacerbated by the effect of carrageenin was almost completely suppressed after 4 hours and was controlled within the first hour following latex protein administration . However, the same latex fraction was completely unable to control the paw edema invoked with dextran stimulation (400 mug), suggesting that the inhibitory effect of the latex is likely to be cell-mediated . Iphosphamide-induced vesical edema in mice was also largely prevented by the latex protein fraction . These results indicate that an effect similar to that of mesna, the classical drug used for this purpose, is operative . Our findings suggest that the sample tested seems to act over a wide spectrum as a novel anti-inflammatory agent . The results also suggest that the active molecules are of a proteinaceous nature despite the presence of numerous secondary metabolites naturally occurring in the C . procera latex. Protein Expr Purif, 2005 Feb, 39(2), 160 - 8 Expression of SMAP-29 cathelicidin-like peptide in bacterial cells by intein-mediated system; Morassutti C et al.; In this work, the intein fusion approach was used for expression and purification of cathelicidin-like peptide SMAP-29 from Escherichia coli cultures . To overcome the high toxicity of the antimicrobial peptide against host cells, both C- and N-terminal fusions with Sce VMA intein were evaluated . The fusion of SMAP-29 with the N-terminus of intein had a dramatic lethal effect . In contrast, chimeric constructs harboring SMAP-29 linked to the C-terminus of intein displayed no significant inhibition of bacterial growth . Expression of intein-SMAP fusion protein was then induced in ER2566 E . coli strain by IPTG addition and different experimental conditions were tested in order to optimize the recovery of the soluble protein complex . Peptide purification was carried out by affinity chromatography: the chitin binding domain linked to intein was used to immobilize the chimeric protein on a chitin column and intein-mediated splicing of target peptide was obtained by thiol addition . Microbroth dilution assay showed that recombinant SMAP-29 displayed a high, dose-dependent bactericidal activity . These data demonstrate that the fusion of SMAP-29 with C-intein was able to inactivate the antimicrobial properties of the cathelicidin peptide allowing the expression of fusion protein in the host cell . The intein-mediated purification supplied an effective way to recover the fusion partner in its proper biologically active form. Eur J Med Chem, 2005 Jan, 40(1), 113 - 23 Biological and physicochemical properties of gemini quaternary ammonium compounds in which the positions of a cross-linking sulfur in the spacer differ; Shirai A et al.; We synthesized two novel gemini quaternary ammonium compounds (gemini QACs), 4,4'-{1,6-(2,5-dithiahexane)}bis(1-alkylpyridinium bromide) and 4,4'-{1,6-(3,4-dithiahexane)}bis(1-alkylpyridinium bromide), which are essentially two dimerized pyridinium salts . Three gemini QACs in which the positions of a cross-linking sulfur in the spacer differ, in addition to the previously described 4,4'-{1,6-(1,6-dithiahexane)}bis(1-alkylpyridinium bromide) to both gemini compounds, were determined for their antimicrobial, hemolytic and surface activities and molecular hydrophobicity . Comparative biological and physicochemical studies concluded that the position of sulfur in the spacer chain for three gemini QAC series influences the surface activity, the hydrophobicity and the electron density of the ammonium nitrogen, and that their biological properties are ascribable to the variation of these parameters caused by the position of the sulfur. Structure (Camb), 2005 Jan, 13(1), 29 - 41 Siderocalin (Lcn 2) Also Binds Carboxymycobactins, Potentially Defending against Mycobacterial Infections through Iron Sequestration; Holmes MA et al.; Siderocalin, a member of the lipocalin family of binding proteins, is found in neutrophil granules, uterine secretions, and at markedly elevated levels in serum and synovium during bacterial infection; it is also secreted from epithelial cells in response to inflammation or tumorigenesis . Identification of high-affinity ligands, bacterial catecholate-type siderophores (such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent, complementing the general antimicrobial innate immune system iron-depletion strategy, sequestering iron as ferric siderophore complexes . Supporting this hypothesis, siderocalin is a potent bacteriostatic agent in vitro under iron-limiting conditions and, when knocked out, renders mice remarkably susceptible to bacterial infection . Here we show that siderocalin also binds soluble siderophores of mycobacteria, including M . tubercu losis: carboxymycobactins . Siderocalin employs a degenerate recognition mechanism to cross react with these dissimilar types of siderophores, broadening the potential utility of this innate immune defense. Bone Marrow Transplant . 2005 Jan 10; {Epub ahead of print} Steroids prevent engraftment syndrome after autologous hematopoietic stem cell transplantation without increasing the risk of infection; Mossad S et al.; Summary:Engraftment syndrome (ES) following autologous hematopoietic stem cell transplantation (AHSCT) is characterized by fever and rash . In January 2002, we instituted steroid prophylaxis for ES from day +4 to +14 . This study was conducted to assess whether this practice increased the risk of infection . In total, 194 consecutive patients were reviewed, 111 did not receive steroid prophylaxis (group A), and 83 did (group B) . Initial antimicrobial prophylaxis was the same in both groups . There were no significant differences between groups in age, gender, race, prior radiation therapy, number of prior chemotherapy regimens, disease status at transplant, mobilization regimen, days of leukopheresis, CD34(+) cell dose, and days to platelet and neutrophil engraftment . Group B had significantly fewer patients with non-Hodgkin's lymphoma and multiple myeloma, shorter median duration from diagnosis to transplant, lower risk of ES, and shorter mean length of hospital stay . The incidence of early and late microbiologically confirmed infections was not significantly different between groups . Types of infections and types of organisms identified were similar in both groups . Hospital readmission rates were similar in both groups . Steroid prophylaxis significantly decreases the risk of ES following AHSCT, and is associated with shortened hospitalization, without increasing risk of infection.Bone Marrow Transplantation advance online publication, 10 January 2005; doi:10.1038/sj.bmt.1704769. Curr Opin Infect Dis, 2004 Dec, 17(6), 533 - 40 Clinical utility of antifungal pharmacokinetics and pharmacodynamics; Andes D; PURPOSE OF REVIEW: Historically the anti-infective dose and dosing interval chosen in clinical trials have been based on an arbitrary goal of maintaining drug levels in serum above the minimum inhibitory concentration of infecting pathogens for most if not all of the dosing interval . Subsequent United States Food and Drug Administration approval of a dosing regimen is then based on clinical success in treatment trials . Over the past decade, the emergence of drug resistance has limited the clinical utility of an increasing number of antimicrobial agents . However, early in drug development clinical trials do not often define the impact of infection with these less susceptible pathogens . The field of pharmacodynamics provides analysis tools that can help predict the likelihood of treatment success with various antimicrobial treatment regimens against susceptible and resistant pathogens . RECENT FINDINGS: In-vitro and animal model studies have begun to define the pharmacodynamic characteristics of a variety of antifungal compounds . In-vivo studies have demonstrated that the pharmacodynamic target associated with efficacy is similar among antifungal drugs within the same class and have shown the importance of considering protein . Analysis of clinical trial data suggests that the pharmacodynamic target identified in animal model studies is predictive of outcomes in humans . SUMMARY: Antifungal pharmacodynamics can be used to understand the relationship between drug dosing, in-vitro susceptibility and treatment efficacy . Consideration of these relationships can be used to optimize dosing regimens with current antifungal agents, to develop susceptibility breakpoint guidelines, and in the design of dosing regimens for drugs in early development. Appl Biochem Biotechnol, 2005 Jan, 120(1), 1 - 14 Expression of Human beta-Defensin-2 With Multiple Joined Genes in Escherichia coli; Xu Z et al.; Human beta-defensin (HBD)-2 is a small cationic peptide with a broad range of antimicrobial activity . In this study, multiple copies of the hBD2 gene were linked in tandem, and a number of different Escherichia coli expression vectors were evaluated, including pQE-30, pBV220, pET-28a(+), and pGEX-4T-2 . No expression of multiple joined genes was detectable in the pQE-30 expression system, whereas in pBV220 with one or two joined hBD2 genes and in pET-28a(+) with one, two, or four copies, target proteins were expressed at a low level . Only when pGEX-4T-2 was applied as expression plasmid with one or two joined hBD2 genes were target proteins expressed in high level, and the expressed fusion proteins account for 26 and 16% of the total insoluble proteins, respectively . In the pGEX-4T-2 and pET-28a(+) expression systems, the effects of multiple joined genes on the growth of host strains and plasmid stability were examined . Host cells containing plasmid carrying fewer copies of hBD2 genes were faster in cell growth . Plasmid stability decreased with an increase in multiple joined genes, which was especially noticeable in the pET-28a(+) system . Furthermore, the presence of glucose in culture medium brought about a positive effect on plasmid stability when using pET28-nhBD2 as expression vectors. Appl Environ Microbiol, 2005 Jan, 71(1), 261 - 9 A clp Gene Homologue Belonging to the Crp Gene Family Globally Regulates Lytic Enzyme Production, Antimicrobial Activity, and Biological Control Activity Expressed by Lysobacter enzymogenes Strain C3; Kobayashi DY et al.; Lysobacter enzymogenes strain C3, a biological control agent for plant diseases, produces multiple extracellular hydrolytic enzymes and displays antimicrobial activity against various fungal and oomycetous species . However, little is known about the regulation of these enzymes or their roles in antimicrobial activity and biocontrol . A study was undertaken to identify mutants of strain C3 affected in extracellular enzyme production and to evaluate their biocontrol efficacy . A single mini-Tn5-lacZ(1)-cat transposon mutant of L . enzymogenes strain C3 that was globally affected in a variety of phenotypes was isolated . In this mutant, 5E4, the activities of several extracellular lytic enzymes, gliding motility, and in vitro antimicrobial activity were reduced . Characterization of 5E4 indicated that the transposon inserted in a clp gene homologue belonging to the Crp gene family of regulators . Immediately downstream was a second open reading frame similar to that encoding acetyltransferases belonging to the Gcn5-related N-acetyltransferase superfamily, which reverse transcription-PCR confirmed was cotranscribed with clp . Chromosomal deletion mutants with mutations in clp and between clp and the acetyltransferase gene verified the 5E4 mutant phenotype . The clp gene was chromosomally inserted in mutant 5E4, resulting in complemented strain P1 . All mutant phenotypes were restored in P1, although the gliding motility was observed to be excessive compared with that of the wild-type strain . clp mutant strains were significantly affected in biological control of pythium damping-off of sugar beet and bipolaris leaf spot of tall fescue, which was partially or fully restored in the complemented strain P1 . These results indicate that clp is a global regulatory gene that controls biocontrol traits expressed by L . enzymogenes C3. Yi Chuan, 2003 Mar, 25(2), 198 - 200 {Use of PCR related methods in detection of gene mutation.}; Yan ZQ et al.; Many inherited diseases and drug resistance have been attributed to mutations in corresponding genes.In this paper,several techniques based on PCR used in diagnosis were concluded.The development and research progress of Mismatch PCR were discussed in details.Some information about an assay that we developed for detection of antimicrobial resistance to quinolones was also described. Yi Chuan, 2003 Mar, 25(2), 146 - 50 {Recombination and Fusion Expression of Porcine Defensin Gene PBD-I in E.coli.}; Luo G et al.; The porcine defensin gene PBD-I was amplified by RT-PCR,then the gene was inserted into expression vector PinPoint(TM) Xa-3.Recombinant plasmid named as ppd-1 was transformed into E.Coli JM109,which could effectively produce fusion protein induced with IPTG.The positive clone of PBD-I gene expressed 17kDa fusion protein by SDS-PAGE electrophoresis.Expression of PBD-I gene didn't increase distinctly along with time.The expression of PBD-I gene lays a foundation in research on antimicrobial activities and its mechanism of the defensin. Trends Parasitol, 2005 Jan, 21(1), 35 - 41 Sabotage and exploitation in macrophages parasitized by intracellular protozoans; Denkers EY et al.; Macrophages are crucial in immunity to infection . They possess potent antimicrobial function, and efficiently process and present peptide antigens for T-cell activation . Despite this, the intracellular protozoan parasites Toxoplasma gondii, Trypanosoma cruzi and Leishmania spp . target macrophages for infection . Each has adopted unique strategies to subvert macrophage antimicrobial functions . The parasites sabotage killing activities through sophisticated manipulation of intracellular macrophage signaling pathways . These subversive activities are probably dictated by the need to evade microbicidal effector function, as well as to avoid proinflammatory pathology that can destabilize the host-parasite interaction . The molecular details of how intracellular protozoans manipulate macrophage signal transduction pathways for their own ends are beginning to emerge. Clin Ther, 2004 Nov, 26(11), 1728 - 57 Daptomycin: a cyclic lipopeptide antimicrobial agent; Jeu L et al.; OBJECTIVES: The aims of this article were: to summarize the pharmacology, pharmacokinetics, and efficacy of daptomycin; to explore its safety profile; and to discuss its current and potential roles as an antimicrobial therapy . METHODS: A literature search was conducted using the MEDLINE (1966-August 2004) and International Pharmaceutical Abstracts (1970-August 2004) databases with the search terms daptomycin, LY146032, and lipopeptide antibiotics . Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy and documents submitted to the US Food and Drug Administration were also reviewed . RESULTS: Phase III study results suggest no difference in efficacy or tolerability between daptomycin 4 mg/kg IV QD and vancomycin or semisynthetic penicillins for complicated skin and skin-structure infections . Animal studies suggest daptomycin may be useful for the treatment of endocarditis . Daptomycin is not indicated for pneumonia, with poorer outcomes than conventional treatment It is available as an IV medication and exhibits 92% plasma protein binding in vitro . In healthy adult humans, daptomycin has a volume of distribution of 0.1 L/kg and a plasma elimination half-life of approximately 9 hours, and is eliminated primarily by renal excretion (approximately 54%) . In patients with reduced renal function, including those receiving hemodialysis and peritoneal dialysis, the dose interval should be 48 hours . No dosage adjustment appears to be necessary for mild to moderate hepatic impairment . The use of daptomycin in patients with severe hepatic impairment has not been assessed . The most commonly reported adverse events include constipation, nausea, injection-site reactions, headache, and diarrhea . Patients should also be monitored regularly for skeletal muscle toxicity . CONCLUSIONS: Daptomycin may be useful for complicated skin and skin-structure infections and gram-positive pathogens resistant to conventional antimicrobials . However, limited data are currently available for duration of treatment beyond 14 days and at doses >4 mg/kg QD. APMIS, 2004 Dec, 112(11-12), 838 - 55 Application of molecular genetic methods in macrolide, lincosamide and streptogramin resistance diagnostics and in detection of drug-resistant Mycobacterium tuberculosis; Jalava J et al.; Jalava J, Marttila H . Application of molecular genetic methods in macrolide, lincosamide and streptogramin resistance diagnostics and in detection of drug-resistant Mycobacterium tuberculosis . APMIS 2004;112:838-55.Antimicrobial susceptibility testing has traditionally been based on measurements of minimal inhibitory concentrations of antimicrobials . Molecular genetic studies on antimicrobial resistance have produced a great deal of genetic information which can be used for diagnosis of antimicrobial resistance determinants . Bacteria can acquire resistance to macrolides, lincosamides and streptogramin antibiotics by modification of the target site of the drugs, by active efflux of the drugs, and by inactivation of the drugs . The genetic backgrounds of these resistance mechanisms are well known and several molecular methods for detection of resistance determinants have been developed . Outbreaks of multidrug-resistant tuberculosis have focused international attention on the emergence of Mycobacterium tuberculosis strains that are resistant to antimycobacterial agents . Knowledge of the antimycobacterial resistance genetics and progress in molecular methods has made it possible to develop rapid molecular methods for susceptibility testing . This review presents the genetic background of drug resistance and introduces some methods for genotypic susceptibility testing. Protein Pept Lett, 2005 Jan, 12(1), 49 - 67 Immunocontinuum: perspectives in antimicrobial peptide mechanisms of action and resistance; Yount NY et al.; Antimicrobial peptides are present in organisms spanning virtually every kingdom, and employ sophisticated mechanisms to exert rapid microbicidal action consistent with their key roles in host defense . Offsetting these mechanisms, some microbial pathogens have evolved complex countermeasures to neutralize exposure to and subvert mechanisms of antimicrobial peptides . The following discussion highlights recent advances that offer greater understanding of the mechanisms of action and resistance of antimicrobial peptides. Protein Pept Lett, 2005 Jan, 12(1), 41 - 7 Antimicrobial peptide microbicides targeting HIV; Cole AM; Cationic antimicrobial peptides and proteins are among the earliest molecular effectors of the innate arm of immunity in humans and other vertebrates . This review, inspired by recent emphasis on the development of topical preventatives for sexually transmitted infections, describes antimicrobial peptides and proteins in the context of microbicide design and development . Particular emphasis is placed on the defensin family of peptides. Protein Pept Lett, 2005 Jan, 12(1), 31 - 9 Amphiphilic alpha-helical antimicrobial peptides and their structure/function relationships; Dennison SR et al.; To facilitate microbial membrane invasion, amphiphilic alpha-helical antimicrobial peptides (alpha-AMPs) show a spatial segregation of hydrophobic and hydrophilic residues about the alpha-helical long axis . Here we discuss potential mechanisms by which these peptides are able to disrupt membrane structure and the structural characteristics, which are required for function. Protein Pept Lett, 2005 Jan, 12(1), 27 - 9 Are oblique orientated alpha-helices used by antimicrobial peptides for membrane invasion? Dennison SR, Harris F, Phoenix DA. Oblique orientated alpha-helices are highly specialised protein structural elements that penetrate membranes at a shallow angle and are used to promote membrane destabilisation by a number of protein classes . Here, the use of extended hydrophobic moment methodology shows that the amphibian extrudates, aurein 1.2 and citropin 1.1, may use oblique orientated alpha-helices in their antimicrobial action and that such use may be shared by other antimicrobial peptides . This appears to be the first systematic analysis of these peptides for the possession of oblique orientated alpha-helical structure. Protein Pept Lett, 2005 Jan, 12(1), 19 - 25 Antimicrobial peptides: cooperative approaches to protection; Patrzykat A et al.; Reports of cationic antimicrobial peptides (CAPs) have become standard fare in research literature . But with several hundred peptides described to date, the investigator who tries to navigate the proposed models of their activity is only treated to a generous serving of incongruencies . Rather than acting in isolation as antimicrobial molecules, CAPs also may synergize with other molecules of innate immunity and modulate both innate and adaptive immune systems, thus providing a link between the various mechanisms that result in host protection. Protein Pept Lett, 2005 Jan, 12(1), 13 - 8 Plant defense and antimicrobial peptides; Castro MS et al.; Plants are constantly exposed to a large array of pathogenic organisms and the survival in these conditions demands quick defense responses which include the synthesis of defense peptides and proteins with antimicrobial properties . The main groups of antimicrobial peptides found in plants are thionins, defensins and lipid transfer proteins . They constitute interesting candidates to engineer disease resistance in plants. Protein Pept Lett, 2005 Jan, 12(1), 3 - 11 Insect antimicrobial peptides: structures, properties and gene regulation; Bulet P et al.; Antimicrobial peptides (AMPs) are part of the armament that insects have developed to fight off pathogens . Insect AMPs are typically cationic and often made of less than 100 amino acid residues . Although their structures are diverse, most of the AMPs can be assigned to a limited number of families . The most common structures are represented by peptides assuming a alpha-helical conformation in organic solutions or disulfide-stabilized beta-sheets with or without alpha-helical domains present . The diverse activity spectrum of these peptides may indicate different modes of action . Genetic analysis in the Drosophila model evidenced that multiple signal transduction pathways are activating the genes coding AMPs. Curr Protein Pept Sci, 2005 Jan, 6(1), 85 - 101 Defensins - components of the innate immune system in plants; Lay FT et al.; Plant defensins are small (c.a . 5 kDa), basic, cysteine-rich proteins with antimicrobial activities . They are ubiquitous in plants and form part of the innate immunity arsenal . Plant defensins are encoded by small multigene families and are expressed in various plant tissues, but are best characterized in seeds . They are typically produced as preproteins, however, a small subset are produced as larger precursors with C-terminal prodomains . To date, the three-dimensional solution structures of seven seed- and two floral-derived defensins have been elucidated by (1)H-NMR spectroscopy . Despite limited amino acid sequence identities, these defensins have comparable global folds with features that are characteristic of the cysteine-stabilized alphabeta (CSalphabeta) motif . Interestingly, their structures are remarkably similar to those of insect defensins and scorpion toxins . Functionally, these proteins exhibit a diverse array of biological activities, although they all serve a common function as defenders of their hosts . This review describes the distribution, biosynthesis, structure, function and mode of action of plant defensins and reflects on their potential in agribiotechnological applications. Curr Protein Pept Sci, 2005 Jan, 6(1), 61 - 75 Bacterial lantibiotics: strategies to improve therapeutic potential; Cotter PD et al.; Lantibiotics are ribosomally-synthesised antimicrobial peptides produced by Gram-positive bacteria that are characterised by the presence of lanthionine and/or methyllanthionine residues . Other unusual post-translationally modified amino acids, most frequently dehydroalanine and dehydrobutyrine, can also be present . While it has been frequently suggested that these peptides have the potential to be utilised in a wide range of medical applications, to date no actual therapeutic applications have been convincingly described . More recently, however, they have been the focus of much attention as a consequence of improved biotechnological capabilities, an improved understanding of lantibiotic biosynthesis and mode of action, and their high specific activity against multi-drug resistant bacteria . This review concerns the fundamental analyses that have revealed the importance of individual amino acids in these peptides and has permitted the implementation of rational mutagenesis strategies ('intelligenetics') to alter individual residues with a view to ultimately widening the active pH range, improve stability, and enhance binding to cell wall targets with the ultimate aim of optimising their antimicrobial activity . It is hoped that as a consequence of this improved knowledge the most suitable application of individual lantibiotics will become apparent . It should also prove possible, in the near future, to generate tailor-made lantibiotics and utilise biosynthetic enzymes to incorporate modified amino acids into non-lantibiotic peptides . In the shorter term, the extensive characterisation of lantibiotics will be instrumental in reassuring drug industry regulators of their safety and facilitate the widespread application of these novel antimicrobial agents in medicine. Curr Protein Pept Sci, 2005 Jan, 6(1), 53 - 60 Defensins - Non-antibiotic Use for Vaccine Development; Biragyn A; Vaccines should elicit protective and long lasting immune memory, which depends on well choreographed responses between innate and acquired immunity . Defensins are small host defense peptides of innate immunity hitherto reported to have antimicrobial activity, which also orchestrate chemotaxis and activation of effector immune cells, including immature dendritic cells . This review analyzes the biological meaning of the immunomodulatory and immunoenhancing features of defensins and their use for the development of novel vaccines to combat cancer and clinically relevant diseases. Curr Protein Pept Sci, 2005 Jan, 6(1), 35 - 51 A Re-evaluation of the Role of Host Defence Peptides in Mammalian Immunity; Bowdish DM et al.; Host defence peptides are found in all classes of life and are a fundamental component of the innate immune response . Initially it was believed that their sole role in innate immunity was to kill invading microorganisms, thus providing direct defence against infection . Evidence now suggests that these peptides play diverse and complex roles in the immune response and that, in higher animals, their functions are not restricted to the innate immune response . In in vitro experiments certain host defence peptides have been demonstrated to be potent antimicrobial agents at modest concentrations, although their antimicrobial activity is often strongly reduced or ablated in the presence of physiological concentrations of ions such as Na(+) and Mg(2+) . In contrast, in experiments done in standard tissue culture media, the composition of which more accurately represents physiological levels of ions, mammalian host defence peptides have been demonstrated to have a number of immunomodulatory functions including altering host gene expression, acting as chemokines and/or inducing chemokine production, inhibiting lipopolysaccharide induced pro-inflammatory cytokine production, promoting wound healing, and modulating the responses of dendritic cells and cells of the adaptive immune response . Animal models indicate that host defence peptides are crucial for both prevention and clearance of infection . As interest in the in vivo functions of host defence peptides is increasing, it is important to consider whether in mammals the direct antimicrobial and immunomodulatory properties observed in vitro are physiologically relevant, especially since many of these activities are concentration dependent . In this review we summarize the concentrations of host defence peptides and ions reported throughout the body and compare that information with the concentrations of peptides that are known have antimicrobial or immunomodulatory functions in vitro. Curr Protein Pept Sci, 2005 Jan, 6(1), 23 - 34 The cathelicidins - structure, function and evolution; Tomasinsig L et al.; The cathelicidin family of host defense peptides includes a group of cationic and usually amphipathic peptides that display a variety of activities related to host defense functions, among which the most acknowledged is a direct antimicrobial activity against various microbial pathogens . All members of this family are synthesized as precursors characterized by an N-terminal cathelin-like domain which is relatively well conserved also in evolutionary distant vertebrates . By contrast, the C-terminal region, which carries the active peptide, appears to be a focus for genetic mechanisms that have selectively generated a considerable sequence diversity . This process is particularly striking in Cetartiodactyls, where repeated gene duplication events and subsequent divergence have produced an array of distinct family members . The corresponding mature cathelicidin peptides are considerably diverse in length, amino acid sequence and structure, variously adopting alpha-helical, elongated or beta-hairpin conformations . The diverse nature of these peptides may account for distinct functions and for a diverse spectrum of activity and/or antimicrobial potency. Curr Protein Pept Sci, 2005 Jan, 6(1), 7 - 21 Primate beta-defensins - Structure, Function and Evolution; Crovella S et al.; Host defense peptides (HDPs) are endogenous antibiotics that play a multifunctional role in the innate immunity of mammals . Among these, beta-defensins contribute to mucosal and epithelial defense, also acting as signal molecules for cellular components of innate and adaptive immunity . Numerous members of this family have been identified in mammalian and avian species, and genomic studies in human and mouse indicate a considerable complexity in their gene organization . Recent reports on the evolution of primate and rodent members of this family indicate quite a complex pattern of variation . In this review we briefly discuss the evolution of mammalian beta-defensins in relation to other types of defensins, and then concentrate on the evolution of beta-defensins 1 to 4 in primates . In particular, the surprisingly varied patterns of evolution, which range from neutral or weakly purifying, to positive selection to a high level of conservation are analyzed in terms of possible genetics, structural or functional implications, as well as to observed variations on the antimicrobial activity in vitro . The role of polymorphisms in the genes encoding for these host defense peptides in determining susceptibility to human diseases are also briefly considered. Curr Pharm Des, 2005, 11(1), 37 - 53 Probiotic research in Australia, New Zealand and the Asia-Pacific region; Crittenden R et al.; Although the epicentres of probiotic research in the past decade have been Japan and Europe, researchers in the Asia-Pacific region have actively contributed to the growing understanding of the intestinal microbial ecosystem, and interactions between gut bacteria, diet and health of the human host . A number of new probiotic strains have been developed in the region that have been demonstrated to have beneficial impacts on health in animal and human trials, including improved protection against intestinal pathogens and modulation of the immune system . Probiotics targeted to animals, including aquaculture, feature heavily in many Asian countries . Developments in probiotic technologies have included microencapsulation techniques, antimicrobial production in fermented meats, and synbiotic combinations . In particular, the impact of resistant starch on the intestinal environment and fermentation by intestinal bacteria has been intensively studied and new probiotic strains selected specifically for synbiotic combinations with resistant starch . This paper provides an overview of probiotic research within Australia, New Zealand and a number of Asian countries, and lists scientists in the Asia-Pacific region involved in various aspects of probiotic research and development. Biomacromolecules, 2005 Jan-Feb, 6(1), 220 - 8 Functionalized Micellar Assemblies Prepared via Block Copolymers Synthesized by Living Free Radical Polymerization upon Peptide-Loaded Resins; Becker ML et al.; Hybrid peptidic-synthetic amphiphilic block copolymers, synthesized by living free radical polymerization (LFRP) on solid support, have been utilized as precursors for nanoscale materials possessing bio-available peptides . LFRP initiators, coupled to the peptide terminus upon the resin, facilitated the growth of homo- and block copolymers via nitroxide mediated radical polymerization (NMRP) or atom transfer radical polymerization (ATRP) . Herein, the versatile solid-support synthesis of the antimicrobial peptide tritrpticin, coupling of living free radical polymerization initiators to the peptide-loaded resin, and the controlled radical polymerization of various monomers to yield amphiphilic diblock copolymers are described . Assembly of the peptidic-synthetic block copolymers into micelles and a preliminary assessment of their in vitro biological properties are detailed. Wien Med Wochenschr, 2004 Nov, 154(21-22), 539 - 47 {On the biological properties of fragrance compounds and essential oils}; Buchbauer G; In the present review the physiological and/or pharmacological properties of essential oils and of single fragrance compounds are discussed . Essential oils are known and have been used since ancient times as natural medicines . As natural products essential oils are dependent on climate and their composition varies according to conditions of soil, to solar irradiation, to harvest time, to production methods, to storage conditions and similar facts which are discussed in chapter 2 of this review . The next chapters deal with the therapeutic use of essential oils in treating diseases, disorders or ailments of the nervous system, against cancer and as penetration enhancers . For space-saving reasons, however, the manifold antimicrobial and antifungal properties of these natural products have been left out . In the last chapter, the pros and cons in the use of essential oils in therapy are also discussed. Circ Res, 2005 Jan 7, 96(1), 15 - 26 Innate immunity and angiogenesis; Frantz S et al.; Activation of an innate immune response is among the first lines of defense after tissue injury . Restoring blood flow to the site of injured tissue is often a necessary prerequisite for mounting an initial immune response to pathogens and for subsequent initiation of a successful repair of wounded tissue . The multiple links among pathogen recognition and suppression, increased angiogenesis, and tissue repair are the topics of this review, which examines of the roles of antimicrobial peptides, mammalian toll-like receptors (TLRs), inflammatory cytokines, and putative "danger" signals, among other signaling pathways, in triggering, sustaining, and then terminating an angiogenic response. Neurosurg Focus . 2004 Dec 15;17(6):E1. General principles in the medical and surgical management of spinal infections: a multidisciplinary approach; Quinones-Hinojosa A et al.; OBJECT: Infections along the spinal axis are characterized by an insidious onset, and the resulting delays in diagnosis are associated with serious neurological consequences and even death . Infections of the spine can affect the vertebral bodies, intervertebral discs, spinal canal, and surrounding soft tissues . Neurological dysfunction occurs when the spinal cord becomes compressed, edematous, or ischemic due to compression by abscess or vascular compromise . The aim of this paper was to detail general diagnostic and management principles for this disease . METHODS: Recent progress in medical technologies, including the development of potent antimicrobial drugs, advanced imaging, and improved surgical methods, have dramatically reduced morbidity and mortality rates for spinal infections; however, debate still exists on the proper management of this disease . In this paper, the authors review the current management protocols for spinal infections at their institution, focusing on medical and surgical treatments for vertebral osteomyelitis, intervertebral disc space infections, and spinal canal and soft-tissue abscesses . CONCLUSIONS: Technological advances in imaging modalities, pharmaceutics, and surgery have resulted in excellent outcomes and have greatly reduced the morbidity and mortality rates associated with spinal infections . Currently, treatment of spinal infections requires a multidisciplinary team that includes infectious diseases experts, neuroradiologists, and spine surgeons . The key to successful management of spinal infections is early detection. Phytomedicine, 2004 Nov, 11(7-8), 701 - 3 Antimicrobial activity of Securidaca longipedunculata; Ajali U et al.; The folk herbal uses of Securidaca longipedunculata in the treatment of diarrhea, boils, gonorrhea, and cough prompted phytochemical analyses and antimicrobial activity screening of extracts of the root . Some flavonoids isolated showed activity against many micro-organisms . These flavonoids were isolated using chromatographic methods. Int J Oral Maxillofac Implants, 2004, 19 Suppl, 128 - 39 Antimicrobial treatment of peri-implant diseases; Heitz-Mayfield LJ et al.; PURPOSE: To review the literature on the treatment of peri-implant diseases . Specific emphasis was placed on the use of antimicrobial therapy, defined as local or systemic administration of antiseptic and/or antibiotic agents . MATERIALS AND METHODS: A search of MEDLINE, the Cochrane Controlled Trials Register, and The Cochrane Health Group Specialized Register was conducted, and articles published in English until July 31, 2003, were included . The results of experimental animal studies and human research are presented . RESULTS: A variety of antimicrobial treatment regimens in combination with nonsurgical or surgical debridement with and without regenerative therapy were reported . Use of antimicrobials varied between studies with respect to type of drug, dosage, delivery system, duration, and commencement of antibiotic administration . Patient compliance and adverse effects related to the antimicrobials were mostly not mentioned . DISCUSSION: While the majority of the case reports and studies presented showed positive outcomes following antimicrobial treatment, there were no non-medicated controls included, so the relative effect of the antimicrobial agent(s) cannot be evaluated . CONCLUSIONS: Although antimicrobials are widely used for the treatment of peri-implant diseases, evidence of their benefit is limited, and randomized, controlled human trials should be initiated where ethically possible . In addition, prospective cohort studies designed to monitor consecutive cases treated using specific treatment protocols are required. Biol Pharm Bull, 2005 Jan, 28(1), 148 - 50 Lipid Membrane-Binding Properties of Tryptophan Analogues of Linear Amphipathic beta-Sheet Cationic Antimicrobial Peptides Using Surface Plasmon Resonance; Kamimori H et al.; Using a surface plasmon resonance (SPR) system, we investigated the lipid membrane-binding properties of four analogues of the 18-residue linear amphipathic beta-sheet cationic antimicrobial peptide (KIGAKI)(3)-NH(2), each of which contains a single isoleucine-to-tryptophan substitution . The results of the SPR study revealed significant differences in the binding characteristics of the peptides depending upon the position of tryptophan residues . These peptides showed higher binding affinity to membranes containing acidic phospholipids than zwitterionic phospholipids . The addition of dimethylsulfoxide to the running buffer was effective in maintaining the solubility of these peptide solutions and obtaining concentration-dependent sensorgrams for the kinetic analysis in this study . The kinetic binding data of SPR correlated closely with both the ability of the peptides to lyse liposomes with the same phospholipid composition and bactericidal activity . The results demonstrate that SPR may be a valuable tool to predict the membrane lytic properties of antimicrobial peptides. J Clin Microbiol, 2005 Jan, 43(1), 140 - 3 Synergy tests by E test and checkerboard methods of antimicrobial combinations against Brucella melitensis; Orhan G et al.; Two different synergy testing methods, the checkerboard and the E test methods, were used to compare the in vitro efficacies of various antimicrobial combinations against 16 Brucella melitensis strains isolated from blood cultures . The rate of agreement of the E test and checkerboard methods was found to be 55% . The most concordant results were found for the streptomycin-doxycycline combination in 12 (75%) tests, in which four strains showed synergistic activity by E test and antagonistic activity by the checkerboard method and in which one strain showed antagonistic activity by both methods . Even though each of these methods uses different conditions and endpoints, the results of both methods frequently agreed. Zhonghua Nei Ke Za Zhi, 2004 Nov, 43(11), 815 - 9 {The adverse reactions of parenteral norvancomycin in 1031 patients.}; Liu Y et al.; OBJECTIVE: To investigate the safety of norvancomycin, and provide basis for its rational use in clinical practice . METHODS: We documented all adverse events occurred in inpatients who receive intravenous infusion of norvancomycin, then we evaluated the relationship between adverse events and norvancomycin and calculated the rates of adverse reaction . RESULTS: 1031 patients were enrolled in this study from March 2002 to June 2003 and 965 of them could be evaluated . 80 adverse reactions occurred in 965 patients who received norvancomycin, giving a total adverse reaction rate of 8.29% . The systemic adverse reactions included renal impairment (4.04%), hepatic impairment (2.38%) and allergic reaction (1.76%) . 15 patients discontinued the treatment because of the adverse reaction . The rates were higher in patients who use other antimicrobial agents concomitantly or whose age >/= 60 years . The rates of renal impairment were higher in those with age >/= 60 years, and the rates of hepatic impairment were higher in whose received this agent longer than 14 days . These factors were independent risk factors (P < 0.05) . CONCLUSIONS: The overall adverse reaction rate of norvancomycin was low . A few patients experienced drug-related reaction, most of these adverse reactions were mild and tolerable . The adverse reactions tended to occur in older patients, those who use other antibiotic concomitantly or those who receive this agent longer than 14 days. Yi Chuan Xue Bao, 2004 Dec, 31(12), 1344 - 50 {Molecular cloning and expression of Attacin from housefly (Musca domestica)}; Geng H et al.; The antimicrobial peptides of insect are the main components of their non-specific immune system, and play a major role in the defense against the foreign disease-related microbes . In this report, a full length cDNA of Attacin, an insect antimicrobial peptide was cloned from housefly (Musca domestica) by homology cloning approach in combine with 3' and 5' RACE . Sequence analysis and phylogenetical study showed that this cDNA contained 778 nucleotides, with a 627 bp open reading frame (ORF) flanked with a 44 bp 5'UTR and a 107 bp 3'UTR . The encoded 208 amino acids housefly Attacin shared a high similarity of 50%-70% with that of the other dipterous insects . In addition, the phylogenetical analysis also indicated that the Attacin from housefly was in the same branch with those of other species, suggesting that they come from the same ancestor . The expression of Attacin transcript was measured by semi-quantitive RT-PCR . The results demonstrated that the expression of housefly Attacin is inducible, and that the level varies with the time of induction and the kinds of pathogens. Dent Assist, 2004 Nov-Dec, 73(6), 20, 22 - 4, 63 Local chemotherapeutics as an adjunct to scaling and root planing; Breault LG et al.; Gingival diseases are the most widely held diseases in America . In some patients, periodontal disease appears in a generalized form, but more often it appears in localized areas . Furthermore, after treatment with scaling and root planing (SRP) in generalized cases, the disease is often reduced to a few local areas in the patient's mouth . Since periodontitis is a bacterial infection with known pathogenic microorganisms, the local delivery of antimicrobials has been considered to be a possible solution for treating and controlling localized forms of periodontal disease . Three current local chemotherapeutic agents are reviewed in this paper: doxycycline gel, chlorhexidine chip and minocycline microspheres . With the advancement of local drug delivery systems, clinicians and their patients have new alternatives for treatment of periodontal disease. J Periodontol, 2004 Nov, 75(11), 1516 - 23 Effects of combined systemic administration of low-dose doxycycline and alendronate on endotoxin-induced periodontitis in rats; Buduneli E et al.; BACKGROUND: Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects . Recently, bisphosphonates have been shown to inhibit alveolar bone resorption . The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet-activating factor (PAF) in endotoxin-induced periodontal breakdown in rats . METHODS: Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS) and 44 adult male Sprague-Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control . Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7-day study period . At the end of the 1-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, LTB4, and PAF levels . The defleshed jaws were analyzed morphometrically for alveolar bone loss . Data were evaluated statistically by using parametric tests . RESULTS: Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P <0.05) . Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE2 and PGF2alpha (P<0.05) . Doxycycline + alendronate + LPS group also significantly reduced LTB4 and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P <0.05) . CONCLUSIONS: Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment . However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice. J Biol Chem . 2005 Jan 4; {Epub ahead of print} A molecular mechanism for LPS protection of gram-negative bacteria from antimicrobial peptides; Papo N et al.; Cationic antimicrobial peptides serve as the first chemical barrier between all organisms and microbes . One of their main targets is the cytoplasmic membrane of the microorganisms . However, it is not yet clear why some peptides are active against one particular bacterial strain but not against others . Recent studies suggested that the lipopolysaccharide outer membrane (LPS) is the first protective layer that actually controls peptide binding and insertion into Gram-negative bacteria . In order to shed light onto these interactions, we synthesized and investigated a 12-mer amphipathic -helical antimicrobial peptide (K5L7) and its diastereomer (4D-K5L7) (containing four D amino acids) . Interestingly, although both peptides strongly bind LPS bilayers and depolarize bacterial cytoplasmic membranes, only the diastereomer kills Gram-negative bacteria . ATR-FTIR, CD, and surface plasmon resonance (SPR) spectroscopies revealed that only the diastereomer penetrates the LPS layer . In contrast, K5L7 binds cooperatively to the polysaccharide chain and the outer phosphate groups . As a result, the self-associated K5L7 is unable to traverse through the tightly packed LPS molecules, revealed by epifluorescence studies with LPS giant unilamellar vesicles (GUVs) . The difference in the peptides' modes of binding is further demonstrated by the ability of the diastereomer to induce LPS miscellization, as shown by transmission electron microscopy . In addition to increasing our understanding of the molecular basis of the protection of bacteria by LPS, this study presents a potential strategy to overcome resistance by LPS, and it should help in the design of antimicrobial peptides for future therapeutic purposes. Drugs Aging, 2004, 21(15), 993 - 1012 Perioperative pharmacotherapy in patients with left ventricular assist devices; Dang NC et al.; Heart failure remains the leading cause of death in Western countries, affecting 4.9 million individuals and causing >300 000 deaths annually in the US alone . The disease is highly prevalent in the elderly population and often follows a course of progressive disability and deterioration . An estimated 15 000 patients with end-stage heart failure could benefit from heart transplant each year . Yet, as a result of a significant shortage of donor organs, only 2500 hearts are donated annually, and approximately one-third of patients awaiting heart transplant die each year . Mechanical circulatory support, primarily in the form of left ventricular assist devices (LVADs), has come to the forefront of treatment for severe congestive heart failure by providing a feasible alternative to patients who might otherwise die awaiting heart transplant . The arrival of LVADs has resulted in a dramatic shift in the management of heart failure, one that will undoubtedly affect and include a vast proportion of elderly patients . While LVADs represent a surgical approach to a disease that has traditionally been managed medically, the pharmacological application throughout the perioperative period remains of critical importance.Five primary classes of drugs bear specific application to the LVAD population: (i) drugs that provide haemodynamic support; (ii) antimicrobials; (iii) anticoagulants and antiplatelets; (iv) agents that promote myocardial recovery; and (v) miscellaneous other medications . Drugs that provide haemodynamic support are subdivided into inotropes, vasopressors and pulmonary vasodilators . Some combination of these medications is usually administered within the perioperative period in order to maintain stable patient haemodynamics and assure proper LVAD function . Antimicrobials are of paramount importance in the pre-, intra- and postoperative periods to minimise the risk of infection, an unfortunately common complication of LVAD therapy that can have potentially morbid consequences . Anticoagulants and antiplatelet medications are necessary for certain types of LVADs and serve to curb the incidence of device thrombus formation and associated embolic phenomena . Pharmacotherapeutic agents that facilitate myocardial recovery are being investigated as adjuncts to LVAD support so that bridge to recovery can become a realistic outcome for a growing number of LVAD patients . The miscellaneous class of medications used with LVADs includes those that minimise the risk of bleeding in select patients and those that enhance proper vitamin and nutrient status in the postoperative period, the attainment of which may serve vital to a successful recovery. Rev Med Chil, 2004 Oct, 132(10), 1211 - 6 {Antimicrobial susceptibility of shiga toxin producing E coli (STEC) strains isolated from human infections and food}; Reyes MS et al.; BACKGROUND: Shiga toxin-producing E coli (STEC) are zoonotic pathogens associated to sporadic episodes of bloody diarrhea, foodborne outbreaks, and Hemolytic Uremic Syndrome (HUS), with worldwide public health impact . Antibiotic use in STEC infections is controversial because of the potential to increase production and secretion of Shiga toxins . AIM: To study the in vitro antimicrobial susceptibility profile of STEC . MATERIAL AND METHODS: The in vitro susceptibility profile against 10 antimicrobials of STEC strains isolated from 29 meat products, 20 patients with diarrhea and 9 HUS patients was studied . Minimal Inhibitory Concentrations (microg/ml) by agar dilution method for ampicillin, cloramphenicol, ciprofloxacin, amikacin, gentamycin, cotrimoxazol, ceftriaxone, tetracycline, fonsfomycin and azihromycin were measured according to NCCLS recommendations . RESULTS: Strains from patients with diarrhea or HUS were all susceptible to the 10 antimicrobials and only 13.7% had intermediate resistance to cloramphenicol . Strains from meat products had a similar susceptibility profile, with only 3.5% resistance to tetracycline, 3.5% intermediate resistance to cloramphenicol and 7% to fosfomycin . All 58 strains were considered resistant to azithromycin (MIC >32 microg/ml) . CONCLUSIONS: Similarity of susceptibility profiles between STEC strains from human and food origin suggests a role of food chain in transmission to humans. Am J Vet Res, 2004 Dec, 65(12), 1730 - 3 Comparison of the use of regulatory assays and high-performance liquid chromatography for detection of residues of ceftiofur sodium metabolites in tissue specimens of culled dairy cattle; Payne MA et al.; OBJECTIVE: To compare the results of regulatory screening and confirmation assays with those of high-performance liquid chromatography (HPLC) in the detection of ceftiofur metabolites in the tissues of culled dairy cattle . ANIMALS: 17 lactating Holstein dairy cows . PROCEDURE: Daily IM injections of ceftiofur sodium were administered at a dose of 2.2 mg of ceftiofur equivalents/kg (n = 6) or 1.0 mg of ceftiofur equivalents/kg (10) for 5 days . Following withdrawal times of 12 hours (high-dose ceftiofur) and either 5 or 10 days (low-dose ceftiofur), cows were slaughtered and liver, kidney, and diaphragmatic muscle specimens were harvested and analyzed by HPLC and standard regulatory methods that included the following assays: the swab test on premises, the fast antimicrobial screen test, the calf antibiotic and sulfa test, and the 7-plate bioassay confirmation test . RESULTS: In all tissue specimens, residues of ceftiofur and desfuroylceftiofur-related metabolites, as measured by HPLC, were less than regulatory tolerance, as defined by the FDA . False-positive screening assay results were more likely for tissue specimens that had been frozen for shipment to a federal laboratory, compared with fresh tissue specimens that were assayed at the slaughter establishment (23% vs 3% false-positive results, respectively) . CONCLUSIONS AND CLINICAL RELEVANCE: The observation that fresh tissues had negative results on screening assays, whereas subsets of the same tissue specimens had false-positive results on screening assays following freezing, suggests that freezing and thawing interferes with microbial inhibition-based regulatory screening assays. Biofactors, 2004, 22(1-4), 319 - 21 Biological activity in traditional Alaska pollack sikhae during low temperature fermentation; Cha YJ et al.; Biological activity was examined on Alaska pollack sikhae produced with 4 treatments (by irradiating at 5 or 10 kGy, or by adding either 0.1 or 0.3% of chitooligosaccharide), compared with control (2-step fermentation only) during fermentation at -2 degrees C . The extracts (500 ppm level) of sikhae had antimicrobial activities against 4 different strains of food poisoning bacteria such as Staphy . aureus, B . subtilis, B . cereus, and L . monocytogenes . Antioxidative activity (EDA(50), 11.55 mg/mL) in control group increased with time up to 60 days of fermentation but decreased thereafter, while those levels in other products were kept within 10.60-18.30 mg/mL ranges during fermentation . Inhibitory activity of angiotensin-I converting enzyme (ACE) (IC(50), 1.51-2.89 mg/mL) in all products was observed during fermentation except at 0 day . Inhibitory activity of xanthine oxidase (XO) (IC(50), 0.65-0.87 mg/mL) in all products also increased with time up to 30 days of fermentation . Without irradiating or adding of chitooligosaccharide, Alaska pollack sikhae showing biological activities was enough by 2-step fermentation and storage at -2 degrees C only. Biofactors, 2004, 21(1-4), 119 - 21 Protective effects of green tea catechins on alveolar macrophages against bacterial infections; Yamamoto Y et al.; Bacterial pneumonia in immunocompromised patients as well as elderly persons often becomes a life threatening disease, even when effective antibiotics are used extensively . In addition, the appearance of antibiotic-resistant bacteria in medical facilities as well as in patients requires another approach to treat such patients besides treatment with antibiotics . In this regard, green tea catechins, such as epigallocatechin gallate (EGCg), may be one of the potential agents for such purpose due to its possible potential immunomodulatory as well as antimicrobial activity . The studies by us showed that EGCg enhanced the in vitro resistance of alveolar macrophages to Legionella pneumophila infection by selective immunomodulatory effects on cytokine formation . Furthermore, the tobacco smoking-induced impairment of alveolar macrophages regarding antibacterial as well as immune activity was also recovered by EGCg treatment . These results indicate that EGCg may be a possible potential immunotherapeutic agent against respiratory infections in immunocompromised patients, such as heavy smokers. Biofactors, 2004, 21(1-4), 55 - 61 Multifunctional peptides encrypted in milk proteins; Meisel H; Many bioactivities of milk are latent in that they are inactive within the protein sequence, requiring enzymatic proteolysis for release of bioactive peptides from milk proteins precursors . Bioactivities of peptides encrypted in major milk proteins are latent until released and activated, e.g . during gastrointestinal digestion or food processing . Bioactive peptides can be produced in vivo following intake of milk proteins, and the proteolytic system of bacterial species used in the production of fermented milk products and cheese can contribute to the liberation of bioactive peptides or precursors thereof . Activated peptides are potential modulators of various regulatory processes in the living system: immunomodulatory peptides stimulate the activities of cells of the immune system and several cytomodulatory peptides inhibit cancer cell growth, antimicrobial peptides kill sensitive microorganisms, angiotensin-I-converting enzyme (ACE)-inhibitory peptides exert an hypotensive effect, opioid peptides are opioid receptor ligands which can modulate absorption processes in the intestinal tract, mineral binding peptides may function as carriers for different minerals, especially calcium . Many milk-derived peptides reveal multifunctional properties, i.e . specific peptide sequences having two or more different biological activities have been reported . Milk protein-derived bioactive peptides are claimed to be health enhancing components that can be used to reduce the risk of disease or to enhance a certain physiological function. Ann Intern Med, 2005 Jan 4, 142(1), 47 - 55 Narrative review: diseases that masquerade as infectious cellulitis; Falagas ME et al.; For cellulitis that does not respond to conventional antimicrobial treatment, clinicians should consider, among other explanations, several noninfectious disorders that might masquerade as infectious cellulitis . Diseases that commonly masquerade as this condition include thrombophlebitis, contact dermatitis, insect stings, drug reactions, eosinophilic cellulitis (the Wells syndrome), gouty arthritis, carcinoma erysipelatoides, familial Mediterranean fever, and foreign-body reactions . Diseases that uncommonly masquerade as infectious cellulitis include urticaria, lymphedema, lupus erythematosus, sarcoidosis, lymphoma, leukemia, Paget disease, and panniculitis . Clinicians should do an initial diagnostic work-up directed by the findings from a detailed history and complete physical examination . In many cases, skin biopsy is the only tool that helps identify the correct diagnosis . Special tests may also be needed. J Leukoc Biol . 2005 Jan 3; {Epub ahead of print} Psoriatic scales: a promising source for the isolation of human skin-derived antimicrobial proteins; Harder J et al.; Patients with psoriasis, a chronic, hyperproliferative and noninfectious skin disease, suffer surprisingly fewer cutaneous infections than would be expected . This observation led us to the hypothesis that a local "chemical shield" in the form of antimicrobial proteins provides psoriatic skin with resistance against infection . We subsequently began a systematic analysis of in vitro antimicrobially active proteins in psoriatic-scale extracts . A biochemical approach with rigorous purification and characterization combined with antimicrobial testing identified a number of mostly new human antibiotic peptides and proteins . In this review, we will focus on the most prominent antimicrobial proteins in psoriatic-scale extracts, which we identified as the S100-protein psoriasin, human beta-defensin 2 (hBD-2), RNase 7, lysozyme, and human neutrophil defensin 1-3 . Apart from these cutaneous, antimicrobial proteins, only a few others, including hBD-3, have been characterized . A great number of minor antimicrobial proteins await further structural characterization. Theriogenology, 2005 Feb, 63(3), 716 - 21 Oregano improves reproductive performance of sows; Allan P et al.; Natural herbs are being explored as alternatives to antimicrobials . The objective of the present study was to determine the effect of strategic addition of oregano to prefarrowing and lactation diets of sows under field conditions . Alternate farrowing groups were given diets containing 1000ppm oregano (dried leaf and flower of Origanum vulgare, enriched with 500g/kg of cold-pressed essential oils of O . vulgare) in prefarrowing and lactation diets . Overall, 801 oregano-treated sows, including 601 primiparous and 1200 multiparous (parity 2.99 +/- 0.43, mean +/- S.E.) and 1809 untreated control sows (705 primiparous and 1104 multiparous; parity 3.04 +/- 0.38), were used . Sows fed oregano had lower annual sow mortality rate (4.02 +/- 0.4% versus 6.92 +/- 1.11%, mean +/- S.E.; P = 0.003), lower sow culling rate during lactation (8.01 +/- 1.11% versus 14.02 +/- 1.33%, P = 0.02), increased farrowing rate (77.02 +/- 2.31% versus 69.91 +/- 2.32%, P = 0.01), increased number of liveborn piglets per litter (10.49 +/- 1.5 versus 9.95 +/- 1.22, P < 0.05), and decreased stillbirth rate (0.909 +/- 0.01 versus 0.807 +/- 0.01, P = 0.05) . In addition, multiparous sows fed oregano had higher (P = 0.04) daily voluntary feed intake compared to non-treated sows (7.7 +/- 0.32kg versus 7.0 +/- 0.42kg, P = 0.04) . Additional studies are needed to elucidate the effects of oregano on the gastrointestinal, immune and urogenital system in swine and to determine if it has any adverse effects. Peptides, 2005 Feb, 26(2), 307 - 16 Effects of pexiganan alone and combined with betalactams in experimental endotoxic shock; Giacometti A et al.; To investigate the efficacy of pexiganan, a 22-residue magainin analog, alone and combined with betalactmas antibiotics in three experimental rat models of Gram-negative septic shock . Adult male Wistar rats were given (i) an intraperitoneal injection of 1mg Escherichia coli 0111:B4 LPS; (ii) 2x10(10)CFU of E . coli ATCC 25922; and (iii) intra-abdominal sepsis induced via cecal ligation and puncture . For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1mg/kg pexiganan, 1mg/kg polymyxin B, 20mg/kg imipenem, 60mg/kg piperacillin alone and combined with 1mg/kg pexiganan . Each group included 15 animals . Lethality, bacterial growth in blood or intra-abdominal fluid, endotoxin and TNF-alpha concentrations in plasma . All compounds reduced the lethality when compared to controls . Piperacillin and imipenem significantly reduced the lethality and the number of E . coli in abdominal fluid compared with saline treatment . Pexiganan showed a slightly lower antimicrobial activity than betalactams even though it achieved a substantial higher decrease in endotoxin and TNF-alpha plasma concentrations than imipenem and piperacillin . No statistically significant differences were noted for antimicrobial and antiendotoxin activities between pexiganan and polymyxin B . Combination between pexiganan and betalactams showed to be the most effective treatment in reducing all variables measured . The use of a novel antimicrobial compound able to bind to LPS associated to potent antibiotics such as betalactams may become an important future consideration for sepsis treatment. Peptides, 2005 Feb, 26(2), 297 - 306 Protegrin structure-activity relationships: using homology models of synthetic sequences to determine structural characteristics important for activity; Ostberg N et al.; The protegrin family of antimicrobial peptides is among the shortest in sequence length while remaining very active against a variety of microorganisms . The major goal of this study is to characterize easily calculated molecular properties, which quantitatively show high correlation with antibacterial activity . The peptides studied have high sequence similarity but vary in activity over more than an order of magnitude . Hence, sequence analysis alone cannot be used to predict activity for these peptides . We calculate structural properties of 62 protegrin and protegrin-analogue peptides and correlate them to experimental activities against six microbe species, as well as hemolytic and cytotoxic activities . Natural protegrins structures were compared with synthetic derivatives using homology modeling, and property descriptors were calculated to determine the characteristics that confer their antimicrobial activity . A structure-activity relationship study of all these peptides provides information about the structural properties that affect activity against different microbial species. Arch Biochem Biophys, 2005 Feb 1, 434(1), 51 - 9 Reaction of ferrous lactoperoxidase with hydrogen peroxide and dioxygen: an anaerobic stopped-flow study; Jantschko W et al.; Lactoperoxidase (LPO) is found in mucosal surfaces and exocrine secretions including milk, tears, and saliva and has physiological significance in antimicrobial defense which involves (pseudo-)halide oxidation . LPO compound III (a ferrous-dioxygen complex) is known to be formed rapidly by an excess of hydrogen peroxide and could participate in the observed catalase-like activity of LPO . The present anaerobic stopped-flow kinetic analysis was performed in order to elucidate the catalytic mechanism of LPO and the kinetics of compound III formation by probing the reactivity of ferrous LPO with hydrogen peroxide and molecular oxygen . It is shown that ferrous LPO heterolytically cleaves hydrogen peroxide forming water and oxyferryl LPO (compound II) . The two-electron oxidation reaction follows second-order kinetics with the apparent bimolecular rate constant being (7.2+/-0.3)x10(4)M(-1)s(-1) at pH 7.0 and 25 degrees C . The H(2)O(2)-mediated conversion of compound II to compound III follows also second-order kinetics (220M(-1)s(-1) at pH 7.0 and 25 degrees C) . Alternatively, compound III is also formed by dioxygen binding to ferrous LPO at an apparent bimolecular rate constant of (1.8+/-0.2)x10(5)M(-1)s(-1) . Dioxygen binding is reversible and at pH 7.0 the dissociation constant (K(D)) of the oxyferrous form is 6muM . The rate constant of dioxygen dissociation from compound III is higher than conversion of compound III to ferric LPO, which is not affected by the oxygen concentration and follows a biphasic kinetics . A reaction cycle including the redox intermediates compound II, compound III, and ferrous LPO is proposed, which explains the observed (pseudo-)catalase activity of LPO in the absence of one-electron donors . The relevance of these findings in LPO catalysis is discussed. Int J Pediatr Otorhinolaryngol, 2005 Jan, 69(1), 117 - 22 A case of the otogenic variant of Lemierre's syndrome with atypical sequelae and a review of pediatric literature; Masterson T et al.; We report a case of an 8-year-old girl who presented with the clinical picture of Lemierre's syndrome (LS) secondary to bilateral mastoiditis . She developed unilateral sensorineural hearing loss (SNHL) along with internal jugular vein (IJV) thrombosis, septic arthritis of her ankle and cervical fasciitis . Combined antimicrobial, anticoagulant and surgical treatment helped reverse all the effects of the sequelae, including nearly all the hearing loss . This is a unique case of this uncommon variant of the syndrome and with an uncommonly reported complication . The literature indicates that pediatric cases are a minority and enforces that successful management rests on awareness of the condition, vigil and promptness of communication of a multidisciplinary pediatric team. Pediatr Infect Dis J, 2004 Dec, 23(12), 1077 - 80 Children's views of microbes: current beliefs about bacteria in Italian grade school children; Milandri M; INTRODUCTION: The misuse of antibacterials and the consequent emergence of resistance indicate that enhanced awareness is required among clinicians, patients and the general population of the collaborative roles of the bacterial ecosystem in health preservation . The objective of this work is to assess school students' knowledge and perception of microbes . METHODS: In preparation for a meeting of health professionals concerning antimicrobial policies, a questionnaire for administration to children from fourth to eighth school grades was developed, exploring their understanding of bacteria, use of antibiotics and hygiene . SETTING: Twenty-eight classrooms in north-central Italy, 7 from fourth to fifth grade and 21 from sixth to eighth grade . RESULTS: Four hundred ninety-nine students with a mean age of 12 years participated in the study . For 60% of the children, the notion of bacteria centered on their harmfulness; only 25% of the interviewees acknowledged a positive role . Antibiotics were perceived as the absolute weapon against both viruses and bacteria by 56% of respondents and most cases of domestic health impairment by 46% of respondents . The proportions of children being treated at the time once or more than once with an antibiotic were 23 and 24%, respectively . Little difference emerged between the notion of cleansing as opposed to disinfecting . CONCLUSION: Children's confused understanding of bacteria and the lack of a specific contribution from schools suggest that health professionals should engage further in educational activities in the community to overcome this problem . Relevant policies may benefit from being targeted at children directly because they are more open to new ideas and can spread in their milieu the idea of a "reconciliation" with the microbial world. Inflamm Bowel Dis, 2004 Nov, 10(6), 763 - 70 Autoantibodies against the bactericidal/permeability-increasing protein from inflammatory bowel disease patients can impair the antibiotic activity of bactericidal/permeability-increasing protein; Schinke S et al.; Bactericidal/permeability-increasing protein (BPI) is an antineutrophil cytoplasmic autoantibody (ANCA) target antigen in inflammatory bowel disease (IBD) . The aim of this study was to characterize binding regions of BPI-autoantibodies and to analyze their ability to block the antibiotic effect of BPI . Sera of 24 ulcerative colitis and Crohn's disease patients were examined in indirect immuno-fluorescence, ANCA enzyme-linked immunosorbent assay (ELISA), and by epitope mapping with 13mer peptides and Western blot for presence of BPI-autoantibodies . IgG preparations were used to determine inhibition of BPI's antimicrobial function by BPI-autoantibodies in a bacterial growth inhibition assay . BPI-autoantibodies were detected by ELISA in 18/24 patients . Epitope mapping and western blotting revealed an additional 3 patients with BPI-autoantibodies . IgG preparations of all patients with Crohn's disease and 9 of 12 ulcerative colitis patients could inhibit the antibiotic function of BPI in vitro as compared with healthy control subjects . Inhibiting BPI-autoantibodies correlated with extraintestinal manifestations, peripheral blood leukocyte counts, and anemia . BPI-autoantibodies recognizing the N-terminal portion were associated with greater mucosal damage and intestinal extent of disease . BPI is a frequent target antigen of autoantibodies in ulcerative colitis and Crohn's disease . Inhibition of the antibiotic function mediated by the N-terminal region of BPI by these autoantibodies may contribute to a proinflammatory environment in IBD patients. Orv Hetil, 2004 Oct 31, 145(44), 2227 - 30 {Role of moxifloxacin in the treatment of community-acquired pneumonia}; Mathe A et al.; INTRODUCTION: Community-acquired pneumonia is a common cause of morbidity and mortality throughout the world . Moxifloxacin, a new generation fluoroquinolone have become an attractive therapeutic alternative in the treatment of community-acquired pneumonia because of its excellent pharmacokinetic parameters and wide antimicrobial spectrum . AIMS: The authors reviewed the role of moxifloxacin in the treatment of community-acquired pneumonia based on their experienc