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interaction of bismuth subsalicylate with fruit juices, ascorbic acid, and thiol-containing substrates to produce soluble bismuth products active against clostridium difficile.bismuth subsalicylate (bss), the active ingredient of pepto-bismol, has been used for many years to treat various disorders of the gastrointestinal tract. using mass spectrometry and the agar dilution method, we determined that insoluble bss interacts with certain dietary components and organic substrates to produce water-soluble products with activity against clostridium difficile.200515616328
analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time pcr.the gut microbiota may contribute to the onset and maintenance of irritable bowel syndrome (ibs). in this study, the microbiotas of patients suffering from ibs were compared with a control group devoid of gastrointestinal (gi) symptoms.200515667495
steroid-refractory ulcerative colitis treated with corticosteroids, metronidazole and vancomycin: a case report.increasing evidence elucidating the pathogenic mechanisms of ulcerative colitis (uc) has accumulated and the disease is widely assumed to be the consequence of genetic susceptibility and an abnormal immune response to commensal bacteria. however evidence regarding an infectious etiology in uc remains elusive.200515667650
quantification of bifidobacterium spp., escherichia coli and clostridium difficile in faecal samples of breast-fed and formula-fed infants by real-time pcr.to determine the influence of either exclusive breast-feeding or formula feeding on both composition and quantity of the gut microbiota in infants, we have developed real-time, quantitative pcr assays for the detection of bifidobacterium spp. and clostridium difficile. furthermore, we have monitored the prevalence and counts of escherichia coli by applying a previously described real-time pcr assay. we found all 100 infants tested to be colonized by bifidobacterium spp. the bifidobacterial count ...200515668012
alternative treatments for clostridium difficile disease: what really works?vancomycin and metronidazole have been used for treating clostridium difficile-associated disease (cdad) for the past 25 years, but approximately 20 % of patients develop recurrent disease. the increasing incidence of nosocomial outbreaks, cases of recurrent cdad and other complications (toxic megacolon, ileus, sepsis) has fuelled the search for different types of treatments. as the understanding of the pathogenesis of this disease has matured, newer treatment strategies that take advantage of t ...200515673502
revised nomenclature of clostridium difficile toxins and associated genes.several different nomenclatures have been applied to the clostridium difficile toxins and their associated genes. this paper summarizes the new nomenclature that has been agreed to by the research groups currently active in the field. the revised nomenclature includes c. difficile toxins and other related large clostridial toxins produced by clostridium sordellii and clostridium novyi, and corresponding toxin genes, as well as toxin production types of c. difficile strains.200515673503
quorum sensing in clostridium difficile: analysis of a luxs-type signalling system.the increasing incidence of clostridium difficile-associated disease, and the problems associated with its control, highlight the need for additional countermeasures. the attenuation of virulence through the blockade of bacterial cell-to-cell communication (quorum sensing) is one potential therapeutic target. preliminary studies have shown that c. difficile produces at least one potential signalling molecule. through the molecule's ability to induce bioluminescence in a vibrio harveyi luxs repor ...200515673504
effect of phage infection on toxin production by clostridium difficile.infection with clostridium difficile and subsequent production of toxins a and b may result in c. difficile-associated diarrhoea and pseudomembranous colitis in hospital patients. the effect of four temperate phages, obtained by induction of clinical c. difficile isolates, on toxin production by c. difficile was determined. none of these phages converted a lysogenized non-toxigenic c. difficile strain to toxin production. one of the accessory toxin genes, tcde, was detected in three phages, phic ...200515673505
generation of an erythromycin-sensitive derivative of clostridium difficile strain 630 (630deltaerm) and demonstration that the conjugative transposon tn916deltae enters the genome of this strain at multiple sites.erythromycin resistance in clostridium difficile strain 630 is conferred by a genetic element termed tn5398 which contains two erm(b) genes: erm1(b) and erm2(b). an erythromycin-sensitive derivative of strain 630 (designated 630deltaerm) was generated by spontaneous mutation after continuous subculture for 30 days. this strain had lost the erm2(b) gene from within tn5398 but retained erm1(b). however, the strain could revert to erythromycin resistance at a frequency of 2.79 x 10(-8), although it ...200515673506
detection of binary-toxin genes (cdta and cdtb) among clostridium difficile strains isolated from patients with c. difficile-associated diarrhoea (cdad) in poland.clostridium difficile a+ b+ and a- b+ strains isolated from stool samples of patients with c. difficile-associated diarrhoea (cdad) were selected from the university hospital warsaw collection. the binary-toxin genes cdta and cdtb were detected by pcr in five of the 41 a+ b+ strains tested, but in none of the 17 a- b+ strains tested, giving 8.6 % prevalence (5/58) of binary-toxin-positive strains. all of the strains that were positive for binary-toxin genes were grouped into toxinotype iv, sugge ...200515673507
prevalence and characteristics of bacteria and host factors in an outbreak situation of antibiotic-associated diarrhoea.antibiotic-associated diarrhoea (aad) represents a clinical entity leading to prolonged hospital stays and diagnostic and therapeutic procedures, and results in additional costs. the aim of the present study was to assess the prevalence and characteristics of different bacteria in stools of patients with aad. the reliability of diagnostic procedures under routine conditions was evaluated. host factors were also analysed. from june 2002 to april 2003 89 cases of diarrhoea were reported at a hospi ...200515673508
an improved protocol for pulsed-field gel electrophoresis typing of clostridium difficile.pulsed-field gel electrophoresis (pfge) is the 'gold standard' technique for bacterial typing and has proved to be discriminatory and reproducible for typing clostridium difficile. nevertheless, a high proportion of strains are non-typable by this technique due to the degradation of the dna during the process. the introduction of several modifications in the pfge standard procedure increased typability from 40% (90 isolates) to 100% (220 isolates) while maintaining the high degree of discriminat ...200515673509
toxigenic status of clostridium difficile in a large spanish teaching hospital.the aim of this study was to evaluate the toxigenic status of circulating strains of clostridium difficile in a large teaching hospital. overall 220 isolates were studied of which 199 (90.5 %) produced both large clostridial toxins detected by conventional methods. ten more strains (4.5 %) had toxin a and b genes detectable by pcr. eleven (5.0 %) variant strains (a- b+) were detected among the isolates studied and 10 strains (4.5 %) had the binary toxin genes (cdta and cdtb).200515673510
pcr ribotyping of clostridium difficile isolates originating from human and animal sources.molecular typing of clostridium difficile isolates from animals and humans may be useful for evaluation of the possibility for interspecies transmission. the objective of this study was to evaluate c. difficile isolates from domestic animals and humans using pcr ribotyping. isolates were also tested using pcr for the presence of genes encoding toxins a and b. one hundred and thirty-three isolates of c. difficile from dogs (n = 92), horses (n = 21) and humans (n = 20), plus one each from a cat an ...200515673511
typing by sequencing the slpa gene of clostridium difficile strains causing multiple outbreaks in japan.previous reports have documented that a surface layer protein (slpa) varies among clostridium difficile isolates. the typing system by sequencing the variable region of the slpa gene was applied to typing c. difficile strains belonging to one pcr ribotype, type smz, which has been identified as frequently causing outbreaks in japan. the pcr ribotype smz strains recovered from patients at different hospitals in japan were examined. among 10 type smz strains tested, three subtypes, smz-1, -2 and - ...200515673512
coexistence of multiple pcr-ribotype strains of clostridium difficile in faecal samples limits epidemiological studies.clostridium difficile is an important cause of antibiotic-associated diarrhoea. the simultaneous presence of different strains in individual faecal samples has not yet been established, but is important for epidemiological studies. recurrences of clostridium difficile-associated diarrhoea (cdad) are observed in 15-20 % of patients and have been reported as relapses or reinfections with a new strain. in a period of 1 year, 28 faecal samples from 23 patients with a first episode of cdad were colle ...200515673513
clinical features of clostridium difficile-associated diarrhoea due to binary toxin (actin-specific adp-ribosyltransferase)-producing strains.toxins a and b are known to be the primary virulence factors of clostridium difficile. other potential virulence factors have been identified such as binary toxin (actin-specific adp-ribosyltransferase toxin, or cdt). a retrospective case-control study was performed in order to identify clinical features and risk factors of c. difficile-associated diarrhoea due to binary toxin-producing strains. each case (a patient with diarrhoea due to binary toxin-producing strain) was compared with two contr ...200515673514
laboratory diagnosis of clostridium difficile-associated diarrhoea: a plea for culture.a routine protocol for diagnosing clostridium difficile-associated diarrhoea (cdad) based on both faecal-cytotoxin detection and toxigenic culture was adopted by the microbiology laboratory of the st luc-ucl university hospital in brussels in 1997. a toxigenic culture is a faecal culture followed, in the case of positivity, by a direct immunoassay on colonies to detect toxin a production. the results obtained over the past 7 years in the hospital are reviewed here. a total of 10,552 diarrhoeal s ...200515673515
immunological properties of surface proteins of clostridium difficile.sera from patients with clostridium difficile-associated disease (cdad) and sera from a control group were analysed by an elisa to detect antibodies directed against four surface proteins and toxins a and b of c. difficile. the surface proteins were the flagellar cap protein flid, the flagellin flic, the adhesin cwp66 divided into two domains, cwp66-nterminal and cwp66-cterminal, and the fibronectin-binding protein fbp68. for each antigen, antibody levels in the cdad patient group and in the con ...200515673516
bovine antibody-enriched whey to aid in the prevention of a relapse of clostridium difficile-associated diarrhoea: preclinical and preliminary clinical data.in a pilot study, the feasibility of immune whey protein concentrate (40%; immune wpc-40) to aid the prevention of relapse of clostridium difficile diarrhoea was evaluated. immune wpc-40 was made from milk after immunization of holstein-frisian cows with c. difficile-inactivated toxins and killed whole-cell c. difficile. immune wpc-40 contained a high concentration of specific siga antibodies, and was effective in neutralizing the cytotoxic effect of c. difficile toxins in cell assays in vitro. ...200515673517
antibiotic treatment for clostridium difficile-associated diarrhea in adults.clostridium difficile (c. difficile) is recognized as a frequent cause of antibiotic-associated diarrhea and colitis.200515674956
peptide antibiotic and actin-binding protein as mixed-type inhibitors of clostridium difficile cdt toxin activities.cdt from clostridium difficile is an adp-ribosyltransferase that causes rapid actin disaggregation and cell death. for efficient catalysis, cdt required specific divalent cations and binding by nad which can be substituted by atp but not adp. increasing isolation of cdt-producing strains prompted our search for antagonists like the anti-c. difficile agents bacitracin and vancomycin which were effective cdt inhibitors. other cdt transferase and glycohydrolase inhibitors with consistently low ic50 ...200515629471
characterization of the cleavage site and function of resulting cleavage fragments after limited proteolysis of clostridium difficile toxin b (tcdb) by host cells.clostridium difficile toxin b (tcdb) is a single-stranded protein consisting of a c-terminal domain responsible for binding to the host cell membrane, a middle part involved in internalization, and the n-terminal catalytic (toxic) part. this study shows that tcdb is processed by a single proteolytic step which cleaves tcdb(10463) between leu(543) and gly(544) and the naturally occurring variant tcdb(8864) between leu(544) and gly(545). the cleavage occurs at neutral ph and is catalysed by a peps ...200515632438
clonal spread of a clostridium difficile strain with a complete set of toxin a, toxin b, and binary toxin genes among polish patients with clostridium difficile-associated diarrhea.clinically relevant clostridium difficile strains usually produce toxins a and b. some c. difficile strains can produce an additional binary toxin. we report clonality among five strains carrying all toxin genes from polish patients with c. difficile-associated diarrhea. in another strain, possible recombination between binary toxin genes is documented.200515635019
3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses.alzheimer's disease (ad) is characterized by extracellular deposits of fibrillar beta-amyloid (abeta) in the brain, a fulminant microglial-mediated inflammatory reaction, and neuronal death. the use of 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors (statins) is associated with a reduced risk of ad, which has been attributed to the cholesterol-lowering actions of these drugs. statins have been reported recently to have anti-inflammatory actions in addition to their classic lipid-lower ...200515647473
cytomegalovirus and clostridium difficile co-infection in severe ulcero-hemorrhagic colitis during induction chemotherapy for acute lymphoblastic leukemia.here we describe the first case of a biopsy-proven cytomegalovirus ulcero-hemorrhagic colitis, associated with clostridium difficile co-infection, occurring during standard induction chemotherapy for common b cell acute lymphoblastic leukemia. we discuss the case and focalize clinical management and diagnostic issues arising from it.200515653455
2-hydroxyisocaproyl-coa dehydratase and its activator from clostridium difficile.the hadbc and hadi genes from clostridium difficile were functionally expressed in escherichia coli and shown to encode the novel 2-hydroxyisocaproyl-coa dehydratase hadbc and its activator hadi. the activated enzyme catalyses the dehydration of (r)-2-hydroxyisocaproyl-coa to isocaprenoyl-coa in the pathway of leucine fermentation. the extremely oxygen-sensitive homodimeric activator as well as the heterodimeric dehydratase, contain iron and inorganic sulfur; besides varying amounts of zinc, oth ...200515654892
pseudomembranous colitis in children.this review presents the microbiology, management and prevention of pseudomembranous colitis (pmc) in children. pmc is commonly associated with prior antibiotic exposure and hospitalization. it is caused almost exclusively by toxins produced by clostridium difficile. the clinical spectrum of this disease may range from a mild, non-specific diarrhea to severe colitis with toxic megacolon, perforation, and death. pmc may affect all age groups, although a lower incidence has been noted in children. ...200515683418
strains and toxins of clostridium. 200515684103
the relationship between hospital infection surveillance and control activities and antibiotic-resistant pathogen rates.antibiotic-resistant pathogen rates are rising in canada and the united states with significant health and economic costs. the examination of the relationship of surveillance and control activities in hospitals with rates of nosocomial methicillin-resistant staphylococcus aureus (mrsa), clostridium difficile -associated diarrhea (cdad), and vancomycin-resistant enterococcus (vre) may identify strategies for controlling this growing problem.200515685127
[what is so difficult ... with c. difficile?]. 200515686207
transcription activation of a uv-inducible clostridium perfringens bacteriocin gene by a novel sigma factor.expression of the plasmid-encoded clostridium perfringens gene for bacteriocin bcn5 was shown to depend in vivo and in vitro on the activity of uvia protein. uvia, also plasmid-encoded, proved to be an rna polymerase sigma factor and was also partly autoregulatory. the uvia gene has two promoters; one provided a uvia-independent, basal level of gene expression while the stronger, uvia-dependent promoter was only utilized after the cell experienced dna damage. as a result, bcn5 synthesis is induc ...200515686564
probiotic therapy of intestinal inflammation and infections.the author presents evidence published during the past year regarding treatment of clinical and experimental intestinal inflammation and infections by probiotic agents.200515687884
clinical inquiries. what are effective therapies for clostridium difficile-associated diarrhea? 200515689297
isolation and characterization of temperate bacteriophages of clostridium difficile.the lack of information on bacteriophages of clostridium difficile prompted this study. three of 56 clinical c. difficile isolates yielded double-stranded dna phages phic2, phic5, phic6, and phic8 upon induction. superinfection and dna analyses revealed relatedness between the phages, while partial sequencing of phic2 showed nucleotide homology to the sequenced c. difficile strain cd630.200515691969
three surveillance strategies for vancomycin-resistant enterococci in hospitalized patients: detection of colonization efficiency and a cost-effectiveness model.to evaluate the cost-effectiveness and detection sensitivity associated with three active surveillance strategies for the identification of patients harboring vancomycin-resistant enterococci (vre) to determine which is the most medically and economically useful.200515693407
prebiotic effect of fructo-oligosaccharide supplemented term infant formula at two concentrations compared with unsupplemented formula and human milk.human milk components, including oligosaccharides, affect the gastrointestinal flora of infants. previous studies in adults have demonstrated that fructo-oligosaccharides increase potentially beneficial fecal bacteria, including bifidobacteria. the purpose of this study was to determine the prebiotic effect of infant formula supplemented with fructo-oligosaccharides.200515699689
etiology of diarrhea in pediatric outpatient settings.the frequency with which bacteria cause diarrhea evaluated in ambulatory settings is often unknown. we attempted to determine the microbiologic etiology of diarrhea in a private pediatric practice (site a) and a clinic serving largely immigrant children (site b) and to establish guidelines for bacterial culture.200515702043
a large outbreak of clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use.fluoroquinolones have not been frequently implicated as a cause of clostridium difficile outbreaks. nosocomial c. difficile infections increased from 2.7 to 6.8 cases per 1000 discharges (p < .001). during the first 2 years of the outbreak, there were 253 nosocomial c. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. we conducted an investigation of a large c. difficile outbreak in our hospital to identify risk factors and characterize the outbreak.200515796280
serotonin-induced regulation of the actin network for learning-related synaptic growth requires cdc42, n-wasp, and pak in aplysia sensory neurons.application of clostridium difficile toxin b, an inhibitor of the rho family of gtpases, at the aplysia sensory to motor neuron synapse blocks long-term facilitation and the associated growth of new sensory neuron varicosities induced by repeated pulses of serotonin (5-ht). we have isolated cdnas encoding aplysia rho, rac, and cdc42 and found that rho and rac had no effect but that overexpression in sensory neurons of a dominant-negative mutant of apcdc42 or the crib domains of its downstream ef ...200515797550
inhibition of clostridium difficile toxin a-induced colitis in rats by apaza.a new compound, apaza, consisting of a molecule of 5-aminosalicylic acid linked to one molecule of 4-aminophenylacetic acid by an azo bond, was testedfor its ability to inhibit acute colitis in rats caused by clostridium difficile toxin a. when administered chronically for 5 days in drinking water, apaza significantly inhibited toxin a-induced myeloperoxidase activity, luminal fluid accumulation, and structural damage to the colon at doses of from 1 to 100 mg/kg x day. for comparison, sulfasalaz ...200515810644
tylosin-responsive chronic diarrhea in dogs.fourteen dogs had shown chronic or intermittent diarrhea for more than 1 year. diarrhea had been successfully treated with tylosin for at least 6 months but recurred when treatment was withdrawn on at least 2 occasions. tylosin-responsive diarrhea (trd) affects typically middle-aged, large-breed dogs and clinical signs indicate that trd affects both the small and large intestine. treatment with tylosin eliminated diarrhea in all dogs within 3 days and in most dogs within 24 hours. tylosin admini ...200515822561
subtyping of clostridium difficile polymerase chain reaction (pcr) ribotype 001 by repetitive extragenic palindromic pcr genomic fingerprinting.fifty isolates of the most common uk strain of clostridium difficile [polymerase chain reaction (pcr) ribotype 001] were analysed by three pcr-based typing methods in order to determine genomic diversity within this strain that may form the basis of a subtyping method. the three methods used were repetitive extragenic palindromic elements (rep), conserved repetitive dna elements (box), and enterobacterial repetitive pcr intergenic consensus sequences (eric). the performance of each typing method ...200515823658
clostridium difficile infection among health care workers receiving antibiotic therapy. 200515825055
clostridium difficile toxin b activates the egf receptor and the erk/map kinase pathway in human colonocytes.clostridium difficile toxin b (txb) mediates acute inflammatory diarrhea characterized by neutrophil infiltration and intestinal mucosal injury. in a xenograft animal model, txb was shown to induce interleukin (il)-8 gene expression in human colonic epithelium. however, the precise mechanisms of this txb response are unknown. the aim of this study was to investigate the txb-mediated proinflammatory pathway in colonocytes.200515825081
[impact of a non-compulsory antibiotic control program (pacta): cost reductions and decreases in some nosocomial infections].antibiotics account for 30% of hospital pharmacy expenses. more than 50% of the prescriptions are considered inappropriate; hence, programs devoted to optimizing the prescription of antibiotics should be developed. we present the results of a non-compulsory program for the assessment and control of antibiotic treatment in the university hospital 12 de octubre in madrid.200515826540
antibiotic-associated diarrhea in a turkish outpatient population: investigation of 288 cases.oral antibiotics are often prescribed, especially for respiratory tract infections in the community. the widespread use of broad-spectrum antibiotics causes an increased incidence of antibiotic-associated diarrhea (aad). although aad has been studied in hospitalized patients, there is little available information concerning the characteristics of aad in outpatient populations. the aim of this study was to investigate the clinical and laboratory findings of adult patients with community-acquired ...200515828448
clostridium difficile toxins: mechanism of action and role in disease.as the leading cause of hospital-acquired diarrhea, clostridium difficile colonizes the large bowel of patients undergoing antibiotic therapy and produces two toxins, which cause notable disease pathologies. these two toxins, tcda and tcdb, are encoded on a pathogenicity locus along with negative and positive regulators of their expression. following expression and release from the bacterium, tcda and tcdb translocate to the cytosol of target cells and inactivate small gtp-binding proteins, whic ...200515831824
the open anterior paramedian retroperitoneal approach for spine procedures.with the advent of anterior lumbar interbody fusion and artificial disk replacement as common procedures for the treatment of many spinal problems, anterior exposure has become an increasingly popular procedure for general, thoracic, urologic, and vascular surgeons. despite this, the body of literature describing this procedure, especially the general and vascular surgery literature, is lacking.200515837883
prevalence of the ermb gene in clostridium difficile strains isolated at a university teaching hospital from 1987 through 1998.we analyzed 226 strains of clostridium difficile for the presence of erythromycin ribosomal methylase b (ermb) genes. forty-four strains (19.4%) carried ermb genes and were resistant to erythromycin. toxin a and toxin b gene sequences were identified in 81.9% of these 44 strains. strains of c. difficile that carry ermb genes are common etiologic agents of c. difficile-associated diarrhea.200515844079
[reactive arthritis induced by clostridium difficile enteritis].this article reports the case of an acute monoarthritis of the ankle occurring in a hla-b27 positive female patient who presented with diarrhea and fever. we retained the hypothesis of a clostridium difficile colitis, as she had previously received an antibiotic treatment. the culture of the synovial fluid remained sterile, which postulated that this arthritis was reactive. the diagnosis was confirmed by the presence of toxins a and b in the stool and positive culture. the outcome was satisfacto ...200515846952
pseudomembranous colitis presenting as acute colonic obstruction without diarrhea in a patient with gastric burkitt lymphoma.pseudomembranous colitis (pmc) usually manifests as fever and diarrhea in hospitalized patients treated with systemic antibiotics. we described a case of pmc with intestinal obstruction but without diarrhea. a 60-year-old man was hospitalized for chemotherapy for the treatment of burkitt lymphoma of the stomach. the patient became febrile and complained of crampy abdominal pain during the post-chemotherapy nadir. plain abdominal radiography showed some intestinal gas and niveau. because stool cy ...200515849835
c. difficile: will lessons be learned? 200515851697
protecting against clostridium difficile illness. 200515851708
potential elevation of tacrolimus trough concentrations with concomitant metronidazole therapy.to report the occurrence of a potential tacrolimus elevation in a renal transplant recipient after adding metronidazole to the medication regimen.200515855244
multidrug resistance in staphylococcus aureus due to overexpression of a novel multidrug and toxin extrusion (mate) transport protein.efflux is an important mechanism of multidrug resistance (mdr) in bacteria. the multidrug and toxin extrusion (mate) family is the most recently described group of mdr efflux proteins, none of which have previously been identified in staphylococcus aureus. two independently derived s. aureus mutants having efflux-related mdr phenotypes were studied using microarray technology and a marked overexpression of an open reading frame (orf; mepa) encoding a protein homologous with mate family proteins ...200515855507
rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential.rifaximin (4-deoxy-4'-methylpyrido[1',2'-1,2]imidazo- [5,4-c]-rifamycin sv) is a synthetic antibiotic designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal (gi) absorption while retaining good antibacterial activity. both experimental and clinical pharmacology clearly show that this compound is a nonsystemic antibiotic with a broad spectrum of antibacterial action covering gram-positive and gram-negative organisms, both aerobes and anaerobes. being virtually ...200515855748
antibiotic-associated diarrhea and pseudomembranous colitis: are they less common with poorly absorbed antimicrobials?diarrhea is a well-known complication of antibiotic therapy. rates of antibiotic-associated diarrhea (aad) vary from 5 to 25%. some antibiotics are more likely to cause diarrhea than others, specifically, those that are broad spectrum and those that target anaerobic flora. this paper reviews the effects of antibiotics on the fecal flora as well as host factors which contribute to aad. clinical features and treatment of aad are also described. prevention of aad rests on wise antibiotic policies, ...200515855751
depolarization induces rho-rho kinase-mediated myosin light chain phosphorylation in kidney tubular cells.myosin-based contractility plays important roles in the regulation of epithelial functions, particularly paracellular permeability. however, the triggering factors and the signaling pathways that control epithelial myosin light chain (mlc) phosphorylation have not been elucidated. herein we show that plasma membrane depolarization provoked by distinct means, including high extracellular k(+), the lipophilic cation tetraphenylphosphonium, or the ionophore nystatin, induced strong diphosphorylatio ...200515857905
effects of piperacillin/tazobactam on clostridium difficile growth and toxin production in a human gut model.clostridium difficile infection (cdi) is a major cause of morbidity in the nosocomial environment. antimicrobial agents such as the third-generation cephalosporins, lincosamides and aminopenicillins are well known for their propensity to induce cdi, but the definitive reasons why remain to be elucidated. despite their broad spectrum of activity against both aerobic and anaerobic bacteria, the ureidopenicillins remain a class of antimicrobials infrequently associated with the development of cdi.200515860551
statins decrease toll-like receptor 4 expression and downstream signaling in human cd14+ monocytes.anti-inflammatory effects of statins contribute to their clinical benefit. molecular mechanisms underlying these effects have not been well explored. because statins attenuate lipopolysaccharide (lps) responsiveness, we hypothesized that part of the pleiotropic effects are mediated through innate immunity.200515860745
statins potentiate the ifn-gamma-induced upregulation of group iia phospholipase a2 in human aortic smooth muscle cells and hepg2 hepatoma cells.the present study shows that the incubation of human aortic smooth muscle cells (hasmc) and hepg2 cells with atorvastatin and mevastatin as hmg-coa reductase inhibitors potentiated the interferon-gamma (inf-gamma)-induced group iia phospholipase a(2) (spla(2)-iia) expression in a dose- and time-dependent manner. the effect of statins on spla(2)-iia expression was reduced by mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate. inversely, inhibitors of the farnesyl transferase and ...200515863363
diarrhoea developing in hospital patients. 200515868883
the importance of microbiological investigations, medications and artificial feeding in diarrhoea evaluation.diarrhoea in hospitalised patients is usually attributed to medications especially antibiotics, enteral tube feeding or enteropathogenic bacteria particularly clostridium difficile.200515868885
albumin, length of stay, and proton pump inhibitors: key factors in clostridium difficile-associated disease in nursing home patients.to identify risk factors for clostridium difficile-associated disease (cdad) in nursing home patients.200515871884
effect of the prebiotic oligofructose on relapse of clostridium difficile-associated diarrhea: a randomized, controlled study.ten percent to 20% of patients relapse after successful treatment of their clostridium difficile -associated diarrhea. we set out to determine if the prebiotic oligofructose could alter the fecal bacterial flora and, in addition to antibiotic treatment, reduce the rate of relapse from c difficile infection.200515880313
novel cd47-dependent intercellular adhesion modulates cell migration.cd47 is a ubiquitously expressed plasma membrane protein, also known as integrin associated protein, that modulates cell adhesion both through alteration of the avidity of integrin binding and through interaction with its own ligands, the extracellular matrix protein thrombospondin (tsp) and the plasma membrane response regulator sirpalpha1. we now show that cd47 expression on fibroblasts can induce intercellular adhesion resulting in cell aggregation in the absence of active integrins, sirpalph ...200515880429
c. difficile strain 20 times more virulent. 200515883397
the role of leukotriene b4 in clostridium difficile toxin a-induced ileitis in rats.clostridium difficile toxin a is a potent intestinal inflammatory agent that has been shown to act at least partially by neurogenic mechanisms involving activation of the transient receptor potential vanilloid 1 (trpv1) (capsaicin) receptor. we tested the hypothesis that leukotriene b4 (ltb4) mediates the effects of toxin a via activation of the trpv1 receptor.200515887113
proteomic analysis of cell surface proteins from clostridium difficile.clostridium difficile is a bacterium that causes disease of the large intestine, particularly after treatment with antibiotics. the bacterium produces two toxins (a and b) that are responsible for the pathology of the disease. in addition, a number of bacterial virulence factors associated with adhesion to the gut have previously been identified, including the cell wall protein cwp66, the high-molecular weight surface layer protein (hmw-slp) and the flagella. as the genome sequence predicts many ...200515887182
subtyping of clostridium difficile pcr ribotype 001 by rep-pcr and pfge.the rep-pcr (repetitive sequence-based pcr using repetitive extragenic palindromic primers) typing method and a modified pfge method were applied to isolates of clostridium difficile pcr ribotype 001 with the aim of comparing their performance as methods of subtyping this organism. of 200 isolates from 60 hospitals tested by rep-pcr, eight subtypes were identified and labelled as rep-pcr subtypes 001-008. the predominant subtype, rep-pcr subtype 003, accounted for 47% of the total. fifty-two of ...200515888462
relatively poor outcome after treatment of clostridium difficile colitis with metronidazole.clostridium difficile is a frequent cause of serious nosocomial infection. earlier reports have suggested that treatment with metronidazole cured nearly 90% of patients, with only a modest rate of recurrence of infection. in recent years, the rate of response to treatment with this drug has appeared to be much lower.200515889354
increasing risk of relapse after treatment of clostridium difficile colitis in quebec, canada.clinicians who treat patients with clostridium difficile-associated diarrhea (cdad) in quebec, canada, have noted an apparent increase in the proportion of patients who experience relapse.200515889355
metronidazole for clostridium difficile-associated disease: is it okay for mom? 200515889356
saccharomyces cerevisiae fungemia: an emerging infectious disease.saccharomyces cerevisiae is well known in the baking and brewing industry and is also used as a probiotic in humans. however, it is a very uncommon cause of infection in humans.200515889360
the microbial etiologies of diarrhea in hospitalized patients from the puerto rico medical center hospitals.the development of diarrhea in hospitalized patients is a frequently encountered clinical problem, which may be due to infectious or non-infectious causes. the purpose of this study was to identify which common community enteric pathogens, if any, are responsible for diarrheal episodes in hospitalized patients. stool samples from 76 consecutive, hospitalized patients were analyzed utilizing routine bacterial cultures, smears for identification of ova and parasites and enzyme-link immunoadsorbent ...200515895876
angiotensin ii subtype 1 receptor blockade inhibits clostridium difficile toxin a-induced intestinal secretion in a rabbit model.angiotensin ii (ang ii) has been described in the regulation of intestinal secretion and absorption via angiotensin subtype 1 (at(1)) and at(2) receptors, respectively, in rats. we investigated the role that ang ii plays in the rabbit ileal-loop model of clostridium difficile infection. expression of at(1), the more abundant ang ii receptor, was demonstrated in ileal loops, and an at(1) receptor blocker, losartan, inhibited hypersecretion induced by c. difficile toxin a (mean volume : length rat ...200515897995
passive immunisation of hamsters against clostridium difficile infection using antibodies to surface layer proteins.clostridium difficile is a major cause of antibiotic-associated diarrhoea and the primary cause of pseudomembraneous colitis in hospitalised patients. we assessed the protective effect of anti-surface layer protein (slp) antibodies on c. difficile infection in a lethal hamster challenge model. post-challenge survival was significantly prolonged in the anti-slp treated group compared with control groups (p=0.0281 and p=0.0283). the potential mechanism of action of the antiserum was shown to be th ...200515899406
colonization by clostridium difficile of neonates in a hospital, and infants and children in three day-care facilities of kanazawa, japan.the intestinal-carriage rates of clostridium difficile in neonates hospitalized in the university hospital's center for perinatal and reproductive health and in infants and children enrolled in two day-nurseries and a kindergarten were examined. swab samples from the floors of these facilities were also analyzed to determine the extent of environmental contamination by this organism. c. difficile was found in the stool of only one of 40 neonates during the normal 1-week stay in the hospital afte ...200515906260
gi complications in pediatric patients post-bmt.this retrospective study comprehensively examined hepatic and gastrointestinal complications post-bone marrow transplant (bmt) in a heterogeneous group of 132 pediatric patients that underwent 142 transplants. hyperbilirubinemia occurred in 28% of this population with clinically evident jaundice in 16%. acute graft-versus-host disease (gvhd) occurred in 46% of the population, with liver involvement in 39% and intestinal involvement in 60% of those with acute gvhd. veno-occlusive disease (vod) oc ...200515908980
saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial.co-treatment with saccharomyces boulardii appears to lower the risk of antibiotic-associated diarrhoea in adults receiving broad-spectrum antibiotics.200515740542
ca2+-dependent regulation of rho gtpases triggers turning of nerve growth cones.cytoplasmic ca2+ elevation and changes in rho gtpase activity are both known to mediate axon guidance by extracellular factors, but the causal relationship between these two events has been unclear. here we show that direct elevation of cytoplasmic ca2+ by extracellular application of a low concentration of ryanodine, which activated ca2+ release from intracellular stores, upregulated cdc42/rac, but downregulated rhoa, in cultured cerebellar granule cells and human embryonic kidney 293t cells. c ...200515745960
comparison of wild type with recombinant clostridium difficile toxin a.toxins a and b from clostridium difficile are single-chain proteins of 308,000 and 270,000 da, respectively. they possess transferase activity to monoglucosylate proteins of the rho gtpase family whereby rho, rac, and cdc42 are the canonical substrates. for application of these toxins as specific rho gtpase inhibitors the highest possible purity is of crucial interest. we, therefore, expressed recombinant his-tagged toxin a using the bacillus megaterium expression system. specific antisera raise ...200515748809
clarification of article on clostridium difficile--associated colitis. 200515751556
clostridium difficile causing acute renal failure: case presentation and review.clostridium difficile infection is primarily a nosocomial infection but asymptomatic carriers of clostridium difficile can be found in up to 5% of the general population. ampicillin, cephalosporins and clindamycin are the antibiotics that are most frequently associated with clostridium difficile-associated diarrhea or colitis. little is known about acute renal failure as a consequence of clostridium difficile-associated diarrhea.200515754415
molecular mechanisms in uterine epithelium during trophoblast binding: the role of small gtpase rhoa in human uterine ishikawa cells.background: embryo implantation requires that uterine epithelium develops competence to bind trophoblast to its apical (free) poles. this essential element of uterine receptivity seems to depend on a destabilisation of the apico-basal polarity of endometrial epithelium. accordingly, a reorganisation of the actin cytoskeleton regulated by the small gtpase rhoa plays an important role in human uterine epithelial rl95-2 cells for binding of human trophoblastoid jar cells. we now obtained new insigh ...200515757515
regulation of h2o2 generation in thyroid cells does not involve rac1 activation.the h2o2 generating system of the thyrocyte and the o2- generating system of macrophages and leukocytes present numerous functional analogies. the main constituent enzymes belong to the nadph oxidase (nox) family (duox/thox for the thyroid and nox2 /gp91phox for the leukocytes and macrophages), and in both cell types, h2o2 generation is activated by the intracellular generation of ca2+ and diacylglycerol signals. nevertheless, although the controls involved in these two systems are similar, thei ...200515762196
clostridium difficile toxoid vaccine in recurrent c. difficile-associated diarrhea.recurrent c difficile -associated diarrhea (cdad) is associated with a lack of protective immunity to c difficile toxins. a parenteral c difficile vaccine containing toxoid a and toxoid b was reported previously to be safe and immunogenic in healthy volunteers. our aim was to examine whether the vaccine is also well tolerated and immunogenic in patients with recurrent cdad.200515765411
failure of dietary oligofructose to prevent antibiotic-associated diarrhoea.oligofructose is metabolized by bifidobacteria, increasing their numbers in the colon. high bifidobacteria concentrations are important in providing 'colonization resistance' against pathogenic bacteria.200515709999
treating c. difficile. 200515710916
treating c. difficile. 200515710921
structural characterization of the cell wall binding domains of clostridium difficile toxins a and b; evidence that ca2+ plays a role in toxin a cell surface association.clostridium difficile (c.difficile) is a nosocomially acquired intestinal bacillus which can cause chronic diarrhea and life-threatening colitis. the pathogenic effects of the bacillus are mediated by the release of two toxins, a and b. the c-terminal portions of both toxins are composed of 20 and 30 residue repeats known as cell wall binding (cwb) domains. we have cloned and expressed the cwb-domains of toxins a and b and several truncated cwb-domain constructs to investigate their structure an ...200515713474
in vitro activity of ramoplanin against clostridium difficile, including strains with reduced susceptibility to vancomycin or with resistance to metronidazole.we evaluated the in vitro activity of ramoplanin, an antimicrobial compound that inhibits cell wall synthesis by acting at the level of lipid intermediate formation, against clostridium difficile. we included strains with reduced susceptibilities to vancomycin (vancomycin-intermediate [van(i)] strains) or with resistance to metronidazole (mtz(r)), in order to assess the potential utility of ramoplanin for the treatment of c. difficile-associated diarrhea. we tested the activity of ramoplanin aga ...200515728918
monocytes are highly sensitive to clostridium difficile toxin a-induced apoptotic and nonapoptotic cell death.in this study we investigated the in vitro responses of peripheral blood mononuclear preparations and purified monocytes to clostridium difficile toxin a. in contrast to the responses of t and b cells, exposure to toxin a led to a rapid loss of monocytes in a time- and dose-dependent fashion (the majority of cells were lost within 24 h of exposure to >100 ng of toxin per ml). transmission electron microscopy, flow cytometry, and fluorescence microscopy after propidium iodide and hoechst staining ...200515731062
quebec puts up 20 million dollars for c. difficile fight. 200515738479
clostridium difficile toxin a regulates inducible cyclooxygenase-2 and prostaglandin e2 synthesis in colonocytes via reactive oxygen species and activation of p38 mapk.clostridium difficile toxin a induces acute colitis with neutrophil infiltration and up-regulation of numerous pro-inflammatory mediators, but the contribution of cyclooxygenase-2 (cox-2) induction in this infection is unknown. we report here that toxin a induces expression of cox-2 and secretion of prostaglandin e2 (pge2) in a dose- and time-dependent manner in cultured ncm460 human colonocytes and in human intestinal xenografts. this induction was blocked by sb203580, a p38 mapk inhibitor, whi ...200515767259
clostridium difficile--associated diarrhea.clostridium difficile infection is responsible for approximately 3 million cases of diarrhea and colitis annually in the united states. the mortality rate is 1 to 2.5 percent. early diagnosis and prompt aggressive treatment are critical in managing c. difficile-associated diarrhea. major predisposing factors for symptomatic c. difficile colitis include antibiotic therapy; advanced age; multiple, severe underlying diseases; and a faulty immune response to c. difficile toxins. the most common conf ...200515768622
the role of antibiotics in inflammatory bowel disease.broad-spectrum antibiotics are the mainstay of therapy for patients with crohn's disease (cd) who present with localized peritonitis due to a microperforation bacterial overgrowth secondary to chronic strictures. they are essential adjuncts to drainage therapy for cd-associated abscesses and for complicated perineal disease. the lack of well-designed, placebo-controlled trials has led to much skepticism about the efficacy of antibiotics as primary therapy for cd. however, a careful review of the ...200515913511
[risk of superinfection related to antibiotic use. are all antibiotics the same?].the aim of this study was to analyze the effect of using different antibiotics on the risk of acquiring a bacterial or fungal superinfection in hospital-acquired infections. a systematic review of the literature using the pubmed (medline) database from january 1990 to december 2003 was performed. we selected only those studies with at least 25 patients in each arm in which the clinical efficacy of several antibiotics (third generation cephalosporins, fluorquinolones, piperacillin-tazobactam and ...200515915231
ermb determinants and tn916-like elements in clinical isolates of clostridium difficile.erythromycin and tetracycline resistance was analyzed in 37 clostridium difficile clinical isolates. strains of different clonal origins showed different erythromycin and tetracycline resistance determinants and different genetic arrangements of the elements. in strains of recent isolation, the presence of tn916-like elements, never found before in c. difficile clinical isolates, has been demonstrated.200515917571
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