Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0234215 (discomfort)
 24,445 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bowel exhibits reflexes in the absence of CNS input. To do so, epithelial sensory transducers, such as enterochromaffin (EC) cells, activate the mucosal processes of intrinsic (IPANs) and extrinsic primary afferent (sensory) neurons. EC cells secrete serotonin (5-HT) in response to mucosal stimuli. Submucosal IPANs, which secrete acetylcholine and calcitonin gene-related peptide, initiate peristaltic and secretory reflexes and are activated via "5-HT1P" receptors. Release of neurotransmitters is enhanced by 5-HT4 receptors, which are presynaptic and strengthen neurotransmission in prokinetic pathways. 5-HT3 receptors mediate signaling to the CNS and thus ameliorate cancer chemotherapy-associated nausea and the visceral hypersensitivity of diarrhea-predominant irritable bowel syndrome (IBS-D); however, because 5-HT3 receptors also mediate fast ENS neurotransmission and activate myenteric IPANs, they may be constipating. 5-HT4 agonists are prokinetic and relieve discomfort and constipation in IBS-C and chronic constipation. 5-HT4 agonists do not initiate peristaltic and secretory reflexes but strengthen pathways that are naturally activated. Serotonergic signaling in the mucosa and the ENS is terminated by a transmembrane 5-HT transporter, SERT. Mucosal SERT and tryptophan hydroxylase-1 expression are decreased in experimental inflammation, IBS-C, IBS-D, and ulcerative colitis. Potentiation of 5-HT due to the SERT decrease could account for the discomfort and diarrhea of IBS-D, while receptor desensitization may cause constipation. Similar symptoms are seen in transgenic mice that lack SERT. The loss of mucosal SERT may thus contribute to IBS pathogenesis.
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PMID:Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome. 1579 84

Irritable bowel syndrome (IBS), which is characterized by abdominal pain or discomfort that is associated with altered bowel function (diarrhea, constipation, or alteration between the two), is one of several gastrointestinal motility disorders. IBS affects up to one in five North Americans, mostly women. The reason(s) this disorder is reported more often by women than men, and the role of gender and biological sex in the prevalence, pathophysiology, symptom presentation, impact on quality of life, diagnosis, and response to treatment, are poorly understood. The purpose of this article is to review the evidence surrounding the roles of gender and biological sex in IBS.
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PMID:The role of gender and biological sex in irritable bowel syndrome. 1604 8

Functional dyspepsia (FD) refers to unexplained pain or discomfort in the upper abdomen and is commonly seen in gastroenterology practice. The underlying pathophysiologic mechanisms associated with FD are unclear, although traditionally, delayed gastric emptying, visceral hypersensitivity to acid or mechanical distention, and impaired gastric accommodation have been implicated as putative physiologic disturbances. It also remains uncertain whether FD and irritable bowel syndrome are different presentations of the same disorder. Recent data on pathophysiologic mechanisms of FD have focused on postprandial motor disturbances (accelerated gastric emptying, antral-fundic incoordination, and abnormal phasic contractions), alterations of neurohormonal mechanisms in response to a meal, and previous acute infection. Pharmacologic therapies for FD may be guided by these novel mechanisms, as current available therapeutic options are limited. Novel prokinetics and gastric accommodation modulators, visceral analgesics, and agents targeting the neurohormonal response to food ingestion are the next therapeutic frontiers in FD. This review summarizes traditional knowledge and more recent advances in the pathophysiology of FD and potential therapeutic opportunities.
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PMID:Frontiers in functional dyspepsia. 1604 12

In a literature search 16 clinical trials investigating 180-200 mg enteric-coated peppermint oil (PO) in irritable bowel syndrome (IBS) or recurrent abdominal pain in children (1 study) with 651 patients enrolled were identified. Nine out of 16 studies were randomized double blind cross over trials with (n = 5) or without (n = 4) run in and/or wash out periods, five had a randomized double blind parallel group design and two were open labeled studies. Placebo served in 12 and anticholinergics in three studies as comparator. Eight out of 12 placebo controlled studies show statistically significant effects in favor of PO. Average response rates in terms of "overall success" are 58% (range 39-79%) for PO and 29% (range 10-52%) for placebo. The three studies versus smooth muscle relaxants did not show differences between treatments hinting for equivalence of treatments. Adverse events reported were generally mild and transient, but very specific. PO caused the typical GI effects like heartburn and anal/perianal burning or discomfort sensations, whereas the anticholinergics caused dry mouth and blurred vision. Anticholinergics and 5HT3/4-ant/agonists do not offer superior improvement rates, placebo responses cover the range as in PO trials. Taking into account the currently available drug treatments for IBS PO (1-2 capsules t.i.d. over 24 weeks) may be the drug of first choice in IBS patients with non-serious constipation or diarrhea to alleviate general symptoms and to improve quality of life.
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PMID:Peppermint oil in irritable bowel syndrome. 1612 21

Irritable bowel syndrome affects 10 to 15 percent of the U.S. population to some degree. This condition is defined as abdominal pain and discomfort with altered bowel habits in the absence of any other mechanical, inflammatory, or biochemical explanation for these symptoms. Irritable bowel syndrome is more likely to affect women than men and is most common in patients 30 to 50 years of age. Symptoms are improved equally by diets supplemented with fiber or hydrolyzed guar gum, but more patients prefer hydrolyzed guar gum. Antispasmodic agents may be used as needed, but anticholinergic and other side effects limit their use in some patients. Loperamide is an option for treatment of moderately severe diarrhea. Antidepressants have been shown to relieve pain and may be effective in low doses. Trials using alosetron showed a clinically significant, although modest, gain over placebo, but it is indicated only for women with severe diarrhea-predominant symptoms or for those in whom conventional treatment has failed. Tegaserod has an advantage over placebo in constipation-predominant irritable bowel syndrome; it is indicated for up to 12 weeks of treatment in women. However, postmarketing reports of severe diarrhea and ischemic colitis further limit its use. Herbal therapies such as peppermint oil also may be effective in the treatment of irritable bowel syndrome. Therapies should focus on specific gastrointestinal dysfunctions (e.g., constipation, diarrhea, pain), and medications only should be used when nonprescription remedies do not work or when symptoms are severe.
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PMID:Treatment of irritable bowel syndrome. 1722 1

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Characterised by abdominal pain or discomfort, bloating and altered bowel habit, IBS is a chronic recurring condition, typically affecting up to 15% of the Western population, IBS can be subclassified into IBS with constipation (IBS-C), IBS with diarrhoea (IBS-D), or IBS with alternating constipation or diarrhoea symptoms (IBS-A). Conventional clinical diagnosis focuses on excluding all potential organic causes of patient symptoms. However, a positive diagnosis of IBS may be established using published criteria such as the Manning and/or Rome criteria. While these methods are useful to identify patients with IBS who are suitable for enrollment into clinical trials, the criteria are relatively complex and not readily applicable to general practice. In this review we present an 'identify, eliminate, probe' algorithm that may be appropriate to establish a positive diagnosis of patients with IBS-C, as symptoms characteristic of patients in this IBS subgroup are least likely to be confused with symptoms reflecting serious organic disease.
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PMID:A symptom-based approach to making a positive diagnosis of irritable bowel syndrome with constipation. 1686 37

Using a sample of over 125 patients with irritable bowel syndrome (IBS) who were treated with cognitive therapy administered in small groups, we sought to predict end of treatment and 3-month follow-up improvement in two changes indices of gastrointestinal (GI) symptoms (Pain/Discomfort Index which assessed change in abdominal pain, abdominal tenderness and bloating and Bowel Regularity Index which assessed change in diarrhea and constipation). We also sought to predict scores on IBS specific quality of life (QOL) and overall level of psychological distress using the Global Severity Index (GSI) of the Brief Symptom Inventory (BSI). Significant, but modest, levels of prediction were found for prediction of improvement in GI symptoms (4-15% of variance). Stronger significant prediction was obtained for the QOL and global psychological distress measure with R(2)'s ranging from 0.36 to 0.50. A wide variety of demographic, GI symptom, psychological status and psychiatric status variables entered the final prediction equations.
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PMID:Prediction of treatment outcome among patients with irritable bowel syndrome treated with group cognitive therapy. 1641 95

In irritable bowel syndrome (IBS) patients, the relationship between sex and sensitivity to visceral stimuli is incompletely understood. Our aim was to evaluate the effect of sex on perceptual responses to visceral stimulation in IBS. Fifty-eight IBS patients (mean age 42+/-1 yr; 34 men, 24 women) and 26 healthy controls (mean age 38+/-3 yr; 9 men, 17 women) underwent barostat-assisted distensions of the rectum and sigmoid colon. Rectal discomfort thresholds were measured using a randomized, phasic distension paradigm before and after repeated noxious sigmoid stimulation (SIG, 60-mmHg pulses). Sex had a significant effect on rectal discomfort thresholds. Women with IBS were the most sensitive (lower thresholds [27+/-2.7 mmHg] and higher ratings), with significantly lower rectal discomfort thresholds compared with men with IBS (38+/-2.3 mmHg) and healthy women who were the least sensitive (41.9+/-3.2 mmHg; both P<0.01). There were no significant differences in rectal discomfort thresholds between healthy men (34+/-4.3 mmHg) and men with IBS. Across both IBS and control groups, women demonstrated a significant lowering of discomfort thresholds after noxious sigmoid stimulation (P<0.01), while men did not. Sex significantly influences perceptual sensitivity to rectosigmoid distension. Women show greater perceptual responses to this paradigm.
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PMID:Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome. 1657 82

Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder affecting up to 3-15% of the general population in Western countries. It is characterised by unexplained abdominal pain, discomfort and bloating in association with altered bowel habits. The pathophysiology of IBS is considered to be multifactorial, involving disturbances of the brain-gut-axis: IBS has been associated with abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction and mucosal inflammation. Traditional IBS therapy is mainly symptom oriented and often unsatisfactory. Hence, there is a need for new treatment strategies. Increasing knowledge of brain-gut physiology, mechanisms, and neurotransmitters and receptors involved in gastrointestinal motor and sensory function have led to the development of several new therapeutic approaches. This article provides a systematic overview of recently approved or novel medications that show promise for the treatment of IBS; classification is based on the physiological systems targeted by the medication. The article includes agents acting on the serotonin receptor or serotonin transporter system, novel selective anticholinergics, alpha-adrenergic agonists, opioid agents, cholecystokinin antagonists, neurokinin antagonists, somatostatin receptor agonists, neurotrophin-3, corticotropin releasing factor antagonists, chloride channel activators, guanylate cyclase-c agonists, melatonin and atypical benzodiazepines. Finally, the role of probiotics and antibacterials in the treatment of IBS is summarised.
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PMID:Irritable bowel syndrome: recent and novel therapeutic approaches. 1678 93

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that can present with a wide array of symptoms that make treatment difficult. Current therapies are directed at relieving symptoms of abdominal pain or discomfort, bloating, constipation, and diarrhea. Pharmacologic agents used to treat IBS-associated pain include myorelaxants, peppermint oil, and peripherally acting opiates. Dicyclomine and hyoscyamine, the two myorelaxants available in the United States, have not been proven effective in reducing abdominal pain in patients with IBS. The efficacy of peppermint oil is debated, but methodological problems with existing studies preclude definitive judgment. Loperamide is ineffective for relief of abdominal pain. For IBS patients with excessive abdominal bloating, a small number of studies suggest that bacterial eradication with gut-directed antibiotics and bacterial reconstitution with nonpathogenic probiotics may reduce flatulence. For constipation-predominant (C-IBS) symptoms, current treatment options include fiber supplementation, polyethylene glycol, and tegaserod. Soluble fibers (ispaghula, calcium polycarbophil, psyllium) are more effective than insoluble fibers (wheat bran, corn fiber) in alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit in treatment of overall IBS symptoms. Polyethylene glycol increases bowel frequency in chronic constipation, but its overall efficacy against IBS is unclear. Tegaserod, a 5-HT(4) agonist, demonstrates superiority over placebo in improving bowel frequency and stool consistency and alleviating abdominal pain and bloating in women with C-IBS. Overall global symptoms are modestly improved with tegaserod when compared with placebo. Additional agents under investigation for C-IBS include the ClC(2) chloride channel opener lubiprostone, mu-opioid receptor antagonist alvimopan, and 5-HT(4) agonist renzapride. For diarrhea-predominant (D-IBS) symptoms, available therapies include loperamide, alosetron, and clonidine. Alosetron, a 5-HT(3) antagonist, is superior to placebo for reducing bowel frequency, improving stool consistency, and relieving abdominal pain in women with D-IBS. However, alosetron is available under a restricted license because of concerns for ischemic colitis and severe constipation necessitating colectomy. Clonidine may be helpful in alleviating global symptoms for D-IBS patients.
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PMID:Current gut-directed therapies for irritable bowel syndrome. 1683 50


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