Visualization of Transepithelial Passage of the Immunogenic 33-Residue Peptide from α-2 Gliadin in Gluten-Sensitive Macaques

BACKGROUND: Based on clinical, histopathological and serological similarities to human celiac disease (CD), we recently established the rhesus macaque model of gluten sensitivity. In this study, we further characterized this condition based on presence of anti-tissue transglutaminase 2 (TG2) antibodies, increased intestinal permeability and transepithelial transport of a proteolytically resistant, immunotoxic, 33-residue peptide from alpha(2)-gliadin in the distal duodenum of gluten-sensitive macaques. METHODOLOGY/PRINCIPAL FINDINGS: Six rhesus macaques were selected for study from a pool of 500, including two healthy controls and four gluten-sensitive animals with elevated anti-gliadin or anti-TG2 antibodies as well as history of non-infectious chronic diarrhea. Pediatric endoscope-guided pinch biopsies were collected from each animal's distal duodenum following administration of a gluten-containing diet (GD) and again after remission by gluten-free diet (GFD). Control biopsies always showed normal villous architecture, whereas gluten-sensitive animals on GD exhibited histopathology ranging from mild lymphocytic infiltration to villous atrophy, typical of human CD. Immunofluorescent microscopic analysis of biopsies revealed IgG+ and IgA+ plasma-like cells producing antibodies that colocalized with TG2 in gluten-sensitive macaques only. Following instillation in vivo, the Cy-3-labeled 33-residue gluten peptide colocalized with the brush border protein villin in all animals. In a substantially enteropathic macaque with "leaky" duodenum, the peptide penetrated beneath the epithelium into the lamina propria. CONCLUSIONS/SIGNIFICANCE: The rhesus macaque model of gluten sensitivity not only resembles the histopathology of CD but it also may provide a model for studying intestinal permeability in states of epithelial integrity and disrepair

Diclofenac in the Management of E. coli Urinary Tract Infections

E. coli is the main agent of uncomplicated urinarytract infections (UTIs) and accounts for more than 85% ofrecurrent cystitis and at least 35% of recurrent pyelonephritis.Despite the widespread availability of antibiotics, UTIs remainthe most common bacterial infection in the human population.It is currently advised that the clinical administration ofantibiotics against the pathogenic bacteria should beprohibitted due to the emergence of multidrug resistant (MDR)bacterial strains. Therefore, newer and more effectiveantimicrobials are in demand to treat such cases. One hundredand thirty six urine samples were collected from UTI patients.E. coli was isolated from 85 samples, out of which 33% wereresistant to common antibiotics. The isolates were decreasinglyresistant to ampicillin, tobramycin, augmentin, nalidixic acid,cefuroxime, nitrofurantoin, kanamycin, pipemidic acid,chloramphenicol, cefotaxime, cefamendol, ofloxacin,ceftizoxime, norfloxacin and amikacin. The anti-inflammatorydrug diclofenac exhibited significant antibacterial activityagainst common bacterial strains both in vitro and in vivo. Thepresent work was conducted to evaluate the in vitro inhibitoryeffect of this drug on the clinically isolated strains of E. coli inhospitals. All the isolates were sensitive to diclofenac, withMIC values ranging from 5-50 ?g/mL. The MIC90 value of thedrug was 25 ?g/mL. Therefore, it may be suggested thatdiclofenac has the capacity to treat UTI caused by E. coli.7p

Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice

The non-steroidal anti-inflammatory drug diclofenac (DCL) shows noteworthy in vitro and in vivo antimycobacterial activity. The aim of this study was to ascertain whether DCL used in combination with the first-line antitubercular antibiotic streptomycin (STM) synergistically augments its efficacy in vitro as well as in a murine tuberculosis infection model. In vitro minimum inhibitory concentrations (MICs) and synergistic activities of the drugs with respect to standard strains and clinical isolates of Mycobacterium tuberculosis were determined. Swiss albino male mice were intravenously infected with 2.3 × 107 M. tuberculosis H37Rv. Mice were treated with DCL or STM alone as well as in combination for 4 weeks to determine the survival rate, spleen weight and colony-forming unit (CFU) counts in the lungs and spleen. DCL was bactericidal at 40 μg/mL (4× MIC) against M. tuberculosis H37Rv and was synergistic with STM in vitro (fractional inhibitory concentration index 0.37). A dose of 10 μg/g/day DCL or 150 μg/g/day STM for 4 weeks, administered from 1 day post infection, significantly (P < 0.05) lowered bacterial counts and reduced mean spleen weight of mice compared with untreated animals. Simultaneous administration of both agents further decreased CFU counts (P < 0.05) in the lungs and spleen compared with mice receiving STM alone. Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in murine tuberculosis, and further investigations may throw light on new directions to combat multidrug-resistant tuberculosis infections in humans.This work was supported by grants provided by the Korea Research Foundation and Brain Korea 21, South Korea

Triflupromazine: a microbicide non-antibiotic compound

The antipsychotic phenothiazine triflupromazine, possessing a methyl-thio substituent at position 10 and a fluorine moiety at position 2, exhibited significant antibacterial activity against 279 strains of Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) of the drug, according to the agar dilution method, was between 2 and 50 µg/ml for Staphylococcus aureus, and 5 and 100 µg/ml for shigellae and vibrios. Triflupromazine, when injected intraperitoneally into Swiss albino mice at a concentration of 30 µg/mouse (20 g), manifested a significant protection to the mice (p<0.001) when they were challenged with 50 median lethal dose (MLD) of Salmonella typhimurium NCTC 74. Moreover, there was a statistically significant reduction in the number of viable bacteria in organ homogenates and blood of mice treated with this phenothiazine compound

In Vitro and In Vivo Antimycobacterial Activity ofan Antihypertensive Agent Methyl-L-DOPA

Methyl-L-DOPA, an antihypertensive agent, has significant in vitro activity against a variety of atypicalmycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. xenopi and M. marinum, and rarepathogens like M. fortuitum. In the present investigation, the screening of the in vitro activity was further extended bytesting the in vitro activity against a total of 53 different strains of mycobacteria, including 34 clinical isolates of bothdrug-sensitive and drug-resistant Mycobacterium tuberculosis.Most of the strains were inhibited at 10-25 ?g/mLconcentrations of the drug. When methyl-L-DOPA wasinjected into male mice at a concentration of 10 ?g/g bodyweight (20 g each), methyl-L-DOPA significantly protectedthem when challenged with a 50 median lethal dose of M.tuberculosis H37Rv102. According to the ?2test, the in vivodata were highly significant (p<0.01).7p

<i>In vitro </i>and <i>in vivo </i>antimycobacterial activity of antiinflammatory drug, diclofenac sodium

922-927The non-steroidal antiinflammatory drug diclofenac sodium exhibited remarkable inhibitory action against both drug sensitive and drug resistant clinical isolates of Mycobacterium tuberculosis, as well as other mycobacteria. This agent was tested in vitro against 45 different strains of mycobacteria, most of which were inhibited by the drug at 10-25 μg/ml concentration. When tested in vivo, diclofenac, injected at 10 mg/kg body weight of a Swiss strain of white mice, could significantly protect them when challenged with a 50 median lethal dose of M. tuberculosis H37 Rv102. According to Chisquare test, the in vivo data were highly significant (P0.01)

Studies on the antimicrobial potential of the cardiovascular drug lacidipine

The cardiovascular drug lacidipine was screened in vitro for possible antibacterial activity with respect to 389 Gram-positive and Gram-negative bacterial strains. It was noticed that most bacteria (233) failed to grow at 50-200 μg/mL concentrations of the drug. Some strains were inhibited at even lower concentrations. The bacteria could be arranged according to their decreasing order of sensitivity as follows: Staphylococcus aureus, Vibrio cholerae, Salmonella spp., Shigellae, Escherichia coli, Bacillus spp., Klebsiellae and Pseudomonas spp. Lacidipine was found to be bacteriostatic in nature against S. aureus and V. cholerae. When administered to Swiss strain of white mice at doses of 30 and 60 μg/mouse, lacidipine significantly protected the animals challenged with 50 MLD of S. typhimurium NCTC 74. According to the chi-square test, the in vivo data were highly significant (p<0.001).4p