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)

Irritable bowel syndrome (IBS) is one of the most common 'functional' gastrointestinal disorders accounting for 3% of all primary care consultations, with a strong female predominance. Although most of the literature comes from Western industrialized societies, when it has been looked for, this disorder appears to be equally common in the Third World. It is characterized by chronic abdominal pain or discomfort associated with disordered bowel habit and visceral hypersensitivity. Anxiety and somatization are more common in IBS than in the general population and may encourage consultation; however, they correlate poorly with symptoms. Bacterial gastroenteritis may be followed by the development of IBS in 5-10% of patients, depending on the severity of initial illness and prior anxiety or depression. The Rome criteria allow reliable diagnosis provided that there are no 'alarm' features which mandate further investigation. Microscopic colitis and bile salt malabsorption can easily be mistaken for IBS, as can chronic infestations or infections which should be considered, while recognizing that these are extremely uncommon in westernized societies. Some patients respond to exclusion diets as lactose and wheat intolerance are common. Others with prominent anxiety and/or depression respond to psychotherapy or antidepressants. Diarrhoeal symptoms respond to loperamide and 5HT3 receptor antagonists, while constipation responds to 5HT4 agonists. Antispasmodics may have limited benefit in treating pain. Low-dose tricyclic antidepressants are also helpful in alleviating pain and anxiety, even in those without obvious psychiatric disorders. If diagnostic criteria are met, then once diagnosed, new diagnoses rarely appear.
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PMID:Irritable bowel syndrome. 1576 61

Patients complaining of 'chronic diarrhoea' usually mean the passage of loose, urgent stools. Chronic diarrhoea is a feature of malabsorption; it may also be seen in the 'dumping syndrome' which follows gastric surgery, small intestinal bacterial overgrowth, bile salt malabsorption and in malabsorption of simple sugars including most commonly lactose, fructose and sorbitol. Excessively rapid entry of chyme into the small or large intestine generates propulsive motor patterns leading to accelerated transit. Inflammation is associated with decreased normal mixing motor patterns but increased propulsive motility including high amplitude propagated contractions (HAPCs). Evidence for abnormal small intestinal motility in the diarrhoea associated with irritable bowel syndrome (IBS) is conflicting and any difference appears small. Increased colonic HAPCs with increased propulsion is seen in IBS with diarrhoea (IBS-D). Stress-induced colonic motility is increased in IBS-D with hyper-responsiveness to corticotrophin releasing factor (CRF). Long-lasting increases in mucosal serotonin availability may contribute to the chronic diarrhoea seen in IBS-D and coeliac disease. Treatments for abnormal motility in chronic diarrhoea include those designed to correct specific underlying abnormalities including octreotide, antibiotics, colestyramine, specific food avoidance and anti-inflammatory agents. There are also treatments aimed primarily at altering motility directly including opiates, 5HT3 receptor antagonists and amitriptyline.
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PMID:Role of motility in chronic diarrhoea. 1710 87

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a proinflammatory cytokine. We measured the HMGB1 concentration in the sera of mice with chemically induced colitis (DSS; dextran sulfate sodium salt) and found a marked increase. Inhibition of HMGB1 by neutralizing anti-HMGB1 antibody resulted in reduced inflammation in DSS-treated colons. In macrophages, HMGB1 induces several proinflammatory cytokines, such as IL-6, which are regulated by NF-kappaB activation. Two putative sources of HMGB1 were explored: in one, bacterial factors induce HMGB1 secretion from macrophages and in the other, necrotic epithelial cells directly release HMGB1. LPS induced a small amount of HMGB1 in macrophages, but macrophages incubated with supernatant prepared from necrotic cells and containing large amounts of HMGB1 activated NF-kappaB and induced IL-6. Using the colitis-associated cancer model, we demonstrated that neutralizing anti-HMGB1 antibody decreases tumor incidence and size. These observations suggest that HMGB1 is a potentially useful target for IBD treatment and the prevention of colitis-associated cancer.
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PMID:Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer. 1759 6

Antagonists of the corticotropin releasing factor (CRF or CRH) receptor have shown promise for the treatment of anxiety, depression, and irritable bowel syndrome. In the present article, medicinal chemistry developments surrounding small molecule CRF receptor antagonists are reviewed, focusing on publications and patents from mid-2004 through the first quarter of 2006. While the CRF type 2 receptor remains an intractable target, incremental progress has been made in the search for drug-like antagonists of the CRF type 1 receptor. Most recent work has not ventured far from previously-established pharmacophoric topologies. A common theme in recent patent disclosures is the addition of novel polar substituents to known heterocyclic core structures to reduce overall lipophilicity. New disclosures of pharmacokinetic (PK) data for several series of antagonists reveal that achieving appropriate PK remains a challenge for the field. The recent publication of selection patents and patents relating to salt and crystal forms of particular compounds suggests that several second generation compounds are nearing or have entered clinical development.
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PMID:Small molecule antagonists of the corticotropin releasing factor (CRF) receptor: recent medicinal chemistry developments. 1839 72

Electron-donating group-substituted 2-iodoxybenzoic acids (IBXs) such as 5-Me-IBX (1g), 5-MeO-IBX (1h), and 4,5-Me(2)-IBX (1i) were superior to IBX 1a as catalysts for the oxidation of alcohols with Oxone (a trademark of DuPont) under nonaqueous conditions, although Oxone was almost insoluble in most organic solvents. The catalytic oxidation proceeded more rapidly and cleanly in nitromethane. Furthermore, 2-iodoxybenzenesulfonic acid (IBS, 6a) was much more active than modified IBXs. Thus, we established a highly efficient and selective method for the oxidation of primary and secondary alcohols to carbonyl compounds such as aldehydes, carboxylic acids, and ketones with Oxone in nonaqueous nitromethane, acetonitrile, or ethyl acetate in the presence of 0.05-5 mol % of 6a, which was generated in situ from 2-iodobenzenesulfonic acid (7a) or its sodium salt. Cycloalkanones could be further oxidized to alpha,beta-cycloalkenones or lactones by controlling the amounts of Oxone under the same conditions as above. When Oxone was used under nonaqueous conditions, Oxone wastes could be removed by simple filtration. Based on theoretical calculations, we considered that the relatively ionic character of the intramolecular hypervalent iodine-OSO(2) bond of IBS might lower the twisting barrier of the alkoxyperiodinane intermediate 16.
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PMID:2-Iodoxybenzenesulfonic acid as an extremely active catalyst for the selective oxidation of alcohols to aldehydes, ketones, carboxylic acids, and enones with oxone. 1905 13

5-Hydroxytryptamine 1A (5-HT(1A)) receptors have been suggested as a target for the treatment of irritable bowel syndrome (IBS). A recent clinical trial investigating the efficacy of the selective 5-HT(1A) antagonist AZD7371 [3(R)-(N,N-dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate monohydrate] showed no symptomatic improvement in IBS patients. We characterized the mechanisms mediating potential analgesic effects of AZD7371 in a model of colorectal distension (CRD)-induced visceral pain in rats to understand its mechanism of action and the lack of clinical efficacy. Visceromotor and cardiovascular responses (telemetry) were assessed in conscious rats during noxious CRD (80 mm Hg). Effects of AZD7371 (3-300 nmol/kg i.v.; 1-30 micromol/kg p.o.) and a reference 5-HT(1A) antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide maleate salt; 3-300 nmol/kg i.v.), were assessed. Effects of intracerebroventricular AZD7371 were also evaluated. Intravenous AZD7371 or WAY-100635 and oral AZD7371 dose-dependently inhibited visceromotor responses to CRD (ED(50), 203, 231, and 14 micromol/kg, respectively). In telemetrized rats, oral AZD7371 inhibited visceromotor responses to CRD without affecting the concomitant hypertensive and tachycardic responses. Intracerebroventricular AZD7371 did not affect visceromotor responses, whereas it inhibited micturition. None of the doses tested induced visible gross side effects. AZD7371, likely acting at a spinal site, inhibited the visceromotor but not the cardiovascular responses to visceral pain in the CRD model in rats. Although agents effective on multiple pain-related readouts in the CRD model (e.g., pregabalin or clonidine) alleviate IBS symptoms, AZD7371, which is effective on only one pain-related pseudoaffective readout, does not. Data from preclinical CRD models of visceral pain need to be interpreted cautiously as it relates to their clinical translational value.
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PMID:The selective 5-hydroxytryptamine 1A antagonist, AZD7371 [3(R)-(N,N-dicyclobutylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide (R,R)-tartrate monohydrate] (robalzotan tartrate monohydrate), inhibits visceral pain-related visceromotor, but not autonomic cardiovascular, responses to colorectal distension in rats. 1932 32

Some patients with an established diagnosis of Crohn's disease and symptoms compatible with a disease flare do not have evidence of active Crohn's disease by laboratory, endoscopic or radiographic criteria. In clinical trials, approximately 18% of patients with Crohn's disease and moderate to severe clinical symptoms have no evidence of ulceration at colonoscopy. There are multiple other causes of symptoms in patients with Crohn's disease, including the presence of disease complications (stricture, fistula and abscess), complications of surgical resection (bile salt diarrhea, steatorrhoea and small bowel bacterial overgrowth), concomitant irritable bowel syndrome, concomitant infections (Clostridium difficile, cytomegalovirus) and concomitant depression. In conclusion, the clinical impression of gastroenterologists based on the patient's history is frequently incorrect and is an insufficient basis for making therapeutic decisions. Colonoscopy and CT or MRI enterography should be employed routinely prior to any major changes in therapy: (1) before starting steroids, immunosuppressives or biologicals; (2) when patients fail to respond to steroids, immunosuppressives or biologicals; (3) when patients receiving maintenance therapy with immunosuppressives or biologicals relapse; (4) before surgery. Treatment of patients who have no evidence of active disease by imaging with steroids, immunosuppressives or biological agents will not address the cause of the symptoms and will expose the patient to risks that may be unnecessary. These patients should be systematically evaluated for bile acid diarrhoea, steatorrhoea, bacterial overgrowth, irritable bowel syndrome and depression.
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PMID:How to avoid treating irritable bowel syndrome with biologic therapy for inflammatory bowel disease. 2020 1

Bowel symptoms including diarrhoea can be produced when excess bile acids (BA) are present in the colon. This condition, known as bile acid or bile salt malabsorption, has been under recognized, as the best diagnostic method, the (75)Se-homocholic acid taurine (SeHCAT) test, is not available in many countries and is not fully utilized in others. Reduced SeHCAT retention establishes that this is a complication of many other gastrointestinal diseases. Repeated studies show SeHCAT tests are abnormal in about 30% of patients otherwise diagnosed as diarrhoea-predominant irritable bowel syndrome or functional diarrhoea, with an estimated population prevalence of around 1%. Recent work suggests that the condition previously called idiopathic bile acid malabsorption (BAM) is not in fact due to a defect in absorption, but results from an overproduction of BA because of defective feedback inhibition of hepatic bile acid synthesis, a function of the ileal hormone fibroblast growth factor 19 (FGF19). The approach to treatment currently depends on binding excess BA, to reduce their secretory actions, using colestyramine, colestipol and, most recently, colesevelam. Colesevelam has a number of potential advantages that merit further investigation in trials directed at patients with bile acid diarrhoea.
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PMID:Managing bile acid diarrhoea. 2118 Jun 14

This article describes changes in the basic digestive functions (motility, secretion, intraluminal digestion, absorption) that occur during aging. Elderly individuals frequently have oropharyngeal muscle dysmotility and altered swallowing of food. Reductions in esophageal peristalsis and lower esophageal sphincter (LES) pressures are also more common in the aged and may cause gastroesophageal reflux. Gastric motility and emptying and small bowel motility are generally normal in elderly subjects, although delayed motility and gastric emptying have been reported in some cases. The propulsive motility of the colon is also decreased, and this alteration is associated with neurological and endocrine-paracrine changes in the colonic wall. Decreased gastric secretions (acid, pepsin) and impairment of the mucous-bicarbonate barrier are frequently described in the elderly and may lead to gastric ulcer. Exocrine pancreatic secretion is often decreased, as is the bile salt content of bile. These changes represent the underlying mechanisms of symptomatic gastrointestinal dysfunctions in the elderly, such as dysphagia, gastroesophageal reflux disease, primary dyspepsia, irritable bowel syndrome, primary constipation, maldigestion, and reduced absorption of nutrients. Therapeutic management of these conditions is also described. The authors also review the gastrointestinal diseases that are more common in the elderly, such as atrophic gastritis, gastric ulcer, colon diverticulosis, malignant tumors, gallstones, chronic hepatitis, liver cirrhosis, Hepato Cellular Carcinoma (HCC), and chronic pancreatitis.
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PMID:Changes, functional disorders, and diseases in the gastrointestinal tract of elderly. 2247 8

Dietary lifestyle is relevant for prevention and treatment of various colorectal conditions. Colorectal disorders have significant morbidity and mortality in a western-style community, particularly irritable bowel syndrome (IBS), colorectal cancer, haemorrhoids, constipation and diverticular disease. This review addresses how bowel health can be maintained, what foods and dietary lifestyles are associated with risk for disease and what foods are of real value in management. Bowel health is that state where the individual is satisfied with defaecation, the diet does not create undue risk for disease and lumenal contents maintain an intact and functional mucosa. Bowel health depends on a healthy dietary lifestyle, but in particular on an adequate intake of non-digestable dietary polysaccharide. Diet influences biology in part by altering the lumenal environment. Effects such as high butyrate levels, lowered pH, a predominance of 'healthy'over 'unhealthy' bacteria, rapid intestinal transit, high faecal bulk, a non-leaky epithelial barrier, adsorption of dietary carcinogens by fibre, low bile salt concentrations, reduced generation of toxic bile salts or protein derivatives and provision of certain bioactive substances are seen as beneficial. Diet influences future risk for colorectal cancer (vegetables, animal fats, polysaccharides amongst others) and for diverticular disease (fibre). Adequate fibre and resistant starch can improve constipation and anorectal conditions such as fissure and haemorrhoids. The role of diet in managing patients with IBS is complex. Fibre may worsen symptoms in severe cases of IBS, diverticular disease and inflammatory bowel disease. Certain carbohydrates of limited digestibility/absorbability, such as lactose, fructose and sorbitol, can precipitate IBS symptoms. Low fat, high fibre diets may reduce recurrence of colorectal adenomas. Diet has a significant role to play in colorectal disorders.
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PMID:Colorectal disorders: A dietary management perspective. 2439 83


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