thiourea and Urinary-Tract-Infections

We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)3(tpa-κ(3)N)](+)) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli.. Activated PhotoCORM inhibits growth and decreases viability of E. coli EC958, but non-illuminated carbon monoxide-releasing molecule (CORM) is without effect. NADH-supported respiration rates are significantly decreased by activated PhotoCORM, mimicking the effect of dissolved CO gas. CO from the PhotoCORM binds to intracellular targets, namely respiratory oxidases in strain EC958 and a bacterial globin heterologously expressed in strain K-12. However, unlike previously characterized CORMs, the PhotoCORM is not significantly accumulated in cells, as deduced from the cellular manganese content. Activated PhotoCORM reacts avidly with hydrogen peroxide producing hydroxyl radicals; the observed peroxide-enhanced toxicity of the PhotoCORM is ameliorated by thiourea. The PhotoCORM also potentiates the effect of the antibiotic, doxycycline.. The present work investigates for the first time the antimicrobial activity of a light-activated PhotoCORM against an antibiotic-resistant pathogen. A comprehensive study of the effects of the PhotoCORM and its derivative molecules upon illumination is performed and mechanisms of toxicity of the activated PhotoCORM are investigated.. The PhotoCORM allows a site-specific and time-controlled release of CO in bacterial cultures and has the potential to provide much needed information on the generality of CORM activities in biology. Understanding the mechanism(s) of activated PhotoCORM toxicity will be key in exploring the potential of this and similar compounds as antimicrobial agents, perhaps in combinatorial therapies with other agents. Antioxid. Redox Signal. 24, 765-780.

Topics: Aerobiosis; Anti-Bacterial Agents; Coordination Complexes; Escherichia coli; Free Radical Scavengers; Hydrogen Peroxide; Microbial Sensitivity Tests; Microbial Viability; Oxygen Consumption; Photochemical Processes; Thiourea; Ultraviolet Rays; Urinary Tract Infections

The identification of human inflammatory cells that express inducible nitric oxide synthase and the clarification of the role of inducible nitric oxide synthase in human infectious or inflammatory processes have been elusive. In neutrophil-enriched fractions from urine, we demonstrate a 43-fold increase in nitric oxide synthase activity in patients with urinary tract infections compared with that in neutrophil-enriched fractions from noninfected controls. Partially purified inducible nitric oxide synthase is primarily membrane associated, calcium independent, and inhibited by arginine analogues with a rank order consistent with that of purified human inducible nitric oxide synthase. Molecular, biochemical, and immunocytochemical evidence unequivocally identifies inducible nitric oxide synthase as the major nitric oxide synthase isoform found in neutrophils isolated from urine during urinary tract infections. Elevated inducible nitric oxide synthase activity and elevated nitric oxide synthase protein measured in patients with urinary tract infections and treated with antibiotics does not decrease until 6-10 d of antibiotic treatment. The extended elevation of neutrophil inducible nitric oxide synthase during urinary tract infections may have both antimicrobial and proinflammatory functions.

Topics: Adult; Aged; Anti-Bacterial Agents; Arginine; Bacterial Infections; Blotting, Western; Canavanine; Cell Membrane; Citrulline; Female; Guanidines; Humans; Immunohistochemistry; Isoenzymes; Leukocyte Common Antigens; Male; Middle Aged; Neutrophils; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitroarginine; omega-N-Methylarginine; Ornithine; Polymerase Chain Reaction; RNA, Messenger; Sulfonamides; Thiourea; Trifluoperazine; Urinary Tract Infections

A comparison has been made of the activity of three antiseptics that are used as bladder irrigants in the treatment of urinary tract infection in catheterised patients. At the concentrations and exposure times used for bladder irrigation, phenoxyethanol (2:4% v/v) proved to be highly bactericidal against urine-grown cells of all the common urinary pathogens tested. Chlorhexidine (200 microgram/ml) was active against Escherichia coli and produced significant reductions in the viability of Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa but failed to eradicate Providencia stuartii. Exposure to noxythiolin (2.5% v/v) for 20 min had little effect in any of the bacteria, even though all strains tested had been recorded as noxythiolin-sensitive by conventional plate sensitivity tests. Contact with noxythiolin for periods of at least 1-2 hrs was necessary before extensive bactericidal activity was detected. These results provide an explanation of the poor clinical performance of noxythiolin that we have observed.

Topics: Anti-Infective Agents, Urinary; Catheters, Indwelling; Chlorhexidine; Drug Resistance, Microbial; Ethylene Glycols; Humans; Noxythiolin; Therapeutic Irrigation; Thiourea; Urinary Tract Infections

Topics: Aged; Ampicillin; Anti-Infective Agents, Local; Arthritis, Rheumatoid; Cloxacillin; Escherichia coli; Escherichia coli Infections; Female; Humans; Joint Diseases; Joint Prosthesis; Knee; Knee Joint; Methanol; Necrosis; Radiography; Splints; Therapeutic Irrigation; Thiourea; Urinary Tract Infections

Topics: Analgesics; Atropine; Barbiturates; Cystitis; Ephedrine; Female; Humans; Orotic Acid; Parasympatholytics; Pelvic Inflammatory Disease; Pyelitis; Sulfonamides; Thiourea; Urinary Bladder Fistula; Urinary Tract Infections