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)

H(2)S functions as a neuromodulator and exerts anti-inflammatory activities. Recent data indicate that irritable bowel syndrome (IBS) is linked to inflammation of the gastrointestinal tract. In this study, we have investigated the role of a novel H(2)S-releasing derivative of mesalamine (5-amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester, ATB-429) in modulating nociception to colorectal distension (CRD), a model that mimics some features of IBS, in healthy and postcolitic rats. Four graded (0.4-1.6 ml of water) CRDs were produced in conscious rats, and colorectal sensitivity and pain were assessed by measuring the abdominal withdrawal response and spinal c-Fos expression. In healthy rats, ATB-429 dose dependently (25, 50, or 100 mg/kg) attenuated CRD-induced hypersensitivity and significantly inhibited CRD-induced overexpression of spinal c-FOS mRNA, whereas mesalamine had no effect. ATB-429-induced antinociception was reversed by glibenclamide, a ATP-sensitive K(+) (K(ATP)) channel inhibitor. The antinociceptive effect of ATB-429 was maintained in a rodent model of postinflammatory hypersensitivity (4 weeks after colitis induction). At a dose of 100 mg/kg, ATB-429 reversed the allodynic response caused by CRD in postcolitic rats. Colonic cyclooxygenase-2 and interkeukin-1beta mRNA and spinal c-FOS mRNA expression were significantly down-regulated by ATB-429, but not by mesalamine. ATB-429, but not mesalamine, increased blood concentrations of H(2)S in both healthy and postcolitic rats. Taken together, these data suggest that ATB-429 inhibits hypersensitivity induced by CRD in both healthy and postcolitic, allodynic rats by a K(ATP) channel-mediated mechanism. This study provides evidence that H(2)S-releasing drugs might have beneficial effects in the treatment of painful intestinal disorders.
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PMID:5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity. 1685 78

Diverticular disease is one of the most common conditions in the Western world and one of the most common findings identified at colonoscopy. Recently, there has been a significant paradigm shift in our understanding of diverticular disease and its management. The pathogenesis of diverticular disease is thought to be multifactorial and include both environmental and genetic factors in addition to the historically accepted etiology of dietary fiber deficiency. Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome. Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some patients with SUDD, although their role(s) in preventing complications remain unclear. Antibiotic use for acute diverticulitis and elective prophylactic resection surgery are considered more individualized treatment modalities that take into account the clinical status, comorbidities and lifestyle of the patient. Our understanding of the pathogenesis of diverticular disease continues to evolve and is likely to be diverse and multifactorial. Paradigm shifts in several areas of the pathogenesis and management of diverticular disease are explored in this review.
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PMID:Diverticular Disease: An Update on Pathogenesis and Management. 2849 76