Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a series of four experiments, diets containing oosporein at graded concentrations from 0 to 600 microgram/g were fed to male broiler chicks from hatching to 3 weeks of age. At dietary toxin levels of 100 microgram/g and below, no detrimental effects were observed. Dietary oosporein concentrations of 200 microgram/g and above elicited dose-related mortality resulting from severe visceral and articular gout. Three-week cumulative mortality percentages were 0, 13, 30, 57, and 95% for the 0, 200, 300, 400, and 600 microgram/g levels, respectively. Upon necropsy, the prominent lesions observed were massive urate deposits in various tissues, swollen and pale kidneys, dehydration, proventricular enlargement with mucosal necrosis, and a green discoloration of the gizzard lining. The effects on the proventriculus and gizzard occurred at doses as low as 200 microgram/g and were the most sensitive indicators of oosporein-toxicosis. In addition to the proventriculus, the relative weights of the kidney and liver were significantly increased in a dose-related fashion. A significant reduction in 3-week body weight at 400 microgram/g apparently resulted from the lower feed consumption concomitantly observed at this level of dietary toxin. Oosporein also caused an increase in water consumption at 400 and 600 microgram/g. Blood analyses indicated no toxin-related effect on plasma glucose, plasma protein, packed red blood cell volume, hemoglobin, and prothrombin times. The plasma concentration of uric acid was significantly elevated at 400 microgram/g. These data and mechanistic considerations suggest that oosporein should be classified as a nephrotoxin in the broiler chicken.
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PMID:Avian gout caused by oosporein, a mycotoxin produced by Caetomium trilaterale. 732 19

Lesinurad is a selective uric acid reabsorption inhibitor approved for use in combination with xanthine oxidase inhibitors for the treatment of hyperuricemia associated with gout. In vitro, lesinurad was shown to be a weak inhibitor of cytochrome P450 (CYP)2C9 and a weak inducer of CYP3A4. Warfarin is a widely prescribed oral coumarin-based anticoagulant commonly prescribed in gout patients. In an open-label clinical study in healthy adult male subjects, the effects of multiple daily doses of 400 mg lesinurad on the pharmacokinetics and pharmacodynamics of a single dose of 25 mg warfarin (racemic mixture of R- and S- enantiomers) were evaluated. Lesinurad had no effect on the absorption or the exposure (area under the concentration-time curve [AUC] and peak concentration) of the more active S-warfarin enantiomer. A slight reduction (19%) in overall plasma exposure (AUC) was observed for the R-warfarin enantiomer. Lesinurad had no meaningful clinical impact on anticoagulation activity as measured by prothrombin time, activated partial thromboplastin time, and international normalized ratio of prothrombin time and Factor VII clotting activity. Overall, the administration of warfarin in the presence of multiple-dose lesinurad was devoid of clinically significant drug-drug interaction.
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PMID:Lesinurad: Evaluation of Pharmacokinetic and Pharmacodynamic Interactions With Warfarin in Healthy Volunteers. 3075 19