Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes ulcerative colitis and Crohn's disease. Leukotriene B4 is thought to be a prominent proinflammatory mediator in these diseases, in that leukotriene B4 levels are increased in the colonic mucosa of inflammatory bowel disease patients and there is increased polymorphonuclear leukocyte infiltration of these tissues. SC-53228 [(+)-(S)-7-[3-[2(-cyclopropylmethyl)-3-methoxy-4- [(methylamino)carbonyl]phenoxy]propoxy]-3,4-dihydro-8-propyl-2H-1- benzopyran-2-propanoic acid], a second generation LTB4 receptor antagonist, was evaluated for therapeutic efficacy in a rodent model of acute colonic inflammation induced by short chain organic acids, as well as for effects on rodent liver. When given intracolonically to mice, SC-53228 inhibited neutrophil infiltration, assessed by myeloperoxidase (MPO) levels, with an ED50 value of 9 +/- 1.2 mg/kg. When given by gavage, SC-53228 inhibited neutrophil influx in colitic mice with an ED50 value of 30 mg/kg. These results were also confirmed histologically. Furthermore, high dose oral SC-53228 treatment had no effect on liver cytochrome P-450 content, fatty acyl CoA oxidase or liver weight in rats and mice. Together, these data suggest that SC-53228 may be efficacious orally and locally, as well as safe for use in trials for the medical management of IBD.
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PMID:Pharmacological activity of the second generation leukotriene B4 receptor antagonist, SC-53228: effects on acute colonic inflammation and hepatic function in rodents. 854 66

1. To investigate the role of interleukin-1 beta in chronic ulcerative colitis, we quantified interleukin-1 beta steady-state release into the colonic lumen. 2. We studied 26 patients with untreated chronic ulcerative colitis and seven patients with irritable bowel syndrome who served as disease controls. In seven ulcerative colitis patients, the disease was inactive and in 19 it was mild to moderately active, according to clinical and colonoscopic criteria. Seven patients with active colitis were studied before and after 4 weeks of treatment with oral 5-aminosalicylic acid. 3. Colonic perfusions were performed using a double-lumen technique. An isotonic solution was continuously infused 50 cm from the anal verge at 5 ml/min, and was recovered 30 cm distally by siphonage. Interleukin-1 beta was measured by ELISA, polymorphonuclear elastase by immunoactivation and leukotriene B4 by specific RIA. 4. All control patients and five out of seven patients with inactive colitis had undetectable interleukin-1 beta release. In active colitis, the release of interleukin-1 beta was detected in 17 out of 19 patients (median 500 pg/min, interquartiles 270-1582 pg/min, P < 0.01 compared with control subjects and patients with inactive colitis). Elastase and leukotriene B4 release were also significantly increased in active colitis compared with inactive colitis and controls. Leukotriene B4 release was similar in inactive colitis and controls, whereas elastase release was higher in inactive colitis than in controls. Five out of seven patients with colitis improved after treatment with 5-aminosalicylic acid. In all responder patients, interleukin-1 beta became undetectable or declined. 5. Our results demonstrate under conditions in vivo that active colitis is associated with enhanced interleukin-1 beta release into the colonic lumen whereas such release does not occur in remission, supporting the concept that ulcerative colitis flare-ups involve increased interleukin-1 beta production.
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PMID:Intracolonic release in vivo of interleukin-1 beta in chronic ulcerative colitis. 854 67