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)

The Society for Medicines Research gathered an international panel of speakers and about 60 delegates for their symposium September 21, 2006, on Therapeutic Approaches Towards the Treatment of Gastroinstestinal Disorders, at the National Heart and Lung Institute, in London, U.K. The focus of the conference was to discuss therapeutic strategies taken towards the treatment of inflammatory bowel disease, acid related disorders and irritable bowel syndrome. Key note lectures addressed the development of tegaserod, a 5-HT(4) receptor agonist, for the treatment of constipation dominant irritable bowel syndrome (cIBS), the use of tumor necrosis factor alpha (TNFalpha) inhibitors in the treatment of chronic inflammatory diseases, including Crohn's disease, the development of effective inhibitors of gastric acid secretion, the role of alpha(4)beta(7) integrin in the development of Crohn's disease and ulcerative colitis, the parts played by the neuropeptides ghrelin and motilin in the control of gastrointestinal motility, and the role of bacteria in functional gastrointestinal disease.
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PMID:Therapeutic approaches towards the treatment of gastroinstestinal disorders. 1744 Jun 38

General gastrointestinal dysmotility occurs in patients with irritable bowel syndrome (IBS). Ghrelin seems to play an important role in regulating gastrointestinal motility. The present study was undertaken, therefore, to establish the possible role of ghrelin in the pathophysiology of IBS. Thirty-seven patients with IBS (19 had IBS-constipation and 18 IBS-diarrhoea) were included in this study. Ten healthy volunteers served as controls. After overnight fast, blood samples were drawn from patients and controls, and a gastroduodenal endoscopy was performed. Biopsies were taken from oxyntic mucosa and duodenum. Ghrelin cell density was determined by computer image analysis after immunohistochemical staining of the tissues. Total and active ghrelin were detected in tissue extracts and plasma by commercially available RIA and ELISA Kits. The density of ghrelin-immunoreactive cells in the oxyntic mucosa was significantly lower in IBS-constipation and significantly higher in IBS-diarrhoea patients than healthy controls (P<0.0001 and <0.0001, respectively). There was no statistical difference in total or active ghrelin between IBS patients and controls, regarding tissue extracts or plasma. In order to compensate for the increase and decrease in the ghrelin cell density, the synthesis and release of ghrelin may be decreased and increased in IBS-diarrhoea and IBS-constipation patients, respectively. It has been speculated that this compensatory mechanism may be subjected from time to time to fatigue with the subsequent increased and decreased synthesis and release of ghrelin in IBS-diarrhoea and IBS-constipation with a subsequent intermittent diarrhoea or constipation seen in these patients, respectively.
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PMID:Ghrelin in patients with irritable bowel syndrome. 1942 95

We have previously shown that ghrelin is mainly localized to the stomach but also occurs, together with the prokinetic hormone motilin, in endocrine cells in the proximal small intestine. This study explored ghrelin and motilin concentrations in plasma in relation to gastrointestinal motility and whether plasma ghrelin is changed in patients with irritable bowel syndrome (IBS). Nine patients with severe IBS and 10 healthy subjects underwent stationary antro-duodeni-jejunal manometry; blood was sampled during similar motility phases in the two groups. The motility phases were monitored and blood samples were collected during fasting and after food intake. Plasma was analyzed for two forms of ghrelin (octanylated and desoctanylated) as well as for motilin. In IBS patients circulating motilin levels covaried with total ghrelin levels (r=0.90; p<0.004), octanylated ghrelin (r=0.77; p<0.02) and desoctanylated ghrelin (r=0.69; p<0.04). No such correlations were seen in the control group. Octanylated ghrelin comprised 35.3+/-3.9% (mean+/-SEM) of the total circulating ghrelin in the IBS patients compared to 40.4+/-4.5% (mean+/-SEM) in the control group (NS). Ghrelin covaried with motilin in plasma in IBS but not in plasma from healthy subjects. This suggests the two peptides act together in IBS.
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PMID:Covariation of plasma ghrelin and motilin in irritable bowel syndrome. 2033 10

Circadian and seasonal rhythms are a fundamental feature of all living organisms and their organelles. Biological rhythms are responsible for daily food intake; the period of hunger and satiety is controlled by the central pacemaker, which resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and communicates with tissues via bidirectional neuronal and humoral pathways. The molecular basis for circadian timing in the gastrointestinal tract (GIT) involves interlocking transcriptional/translational feedback loops which culminate in the rhythmic expression and activity of a set of clock genes and related hormones. Interestingly, it has been found that clocks in the GIT are responsible for the periodic activity (PA) of its various segments and transit along the GIT; they are localized in special interstitial cells, with unstable membrane potentials located between the longitudinal and circular muscle layers. The rhythm of slow waves is controlled in various segments of the GIT: in the stomach (about 3 cycles per min), in the duodenum (12 cycle per min), in the jejunum and ileum (from 7 to 10 cycles per min), and in the colon (12 cycles per min). The migrating motor complex (MMC) starts in the stomach and moves along the gut causing peristaltic contractions when the electrical activity spikes are superimposed on the slow waves. GIT hormones, such as motilin and ghrelin, are involved in the generation of MMCs, while others (gastrin, ghrelin, cholecystokinin, serotonin) are involved in the generation of spikes upon the slow waves, resulting in peristaltic or segmental contractions in the small (duodenum, jejunum ileum) and large bowel (colon). Additionally, melatonin, produced by neuro-endocrine cells of the GIT mucosa, plays an important role in the internal biological clock, related to food intake (hunger and satiety) and the myoelectric rhythm (produced primarily by the pineal gland during the dark period of the light-dark cycle). This appears to be an endocrine encoding of the environmental light-dark cycle, conveying photic information which is used by organisms for both circadian and seasonal organization. Motor and secretory activity, as well as the rhythm of cell proliferation in the GIT and liver, are subject to many circadian rhythms, mediated by autonomic cells and some enterohormones (gastrin, ghrelin and somatostatin). Disruption of circadian physiology, due to sleep disturbance or shift work, may result in various gastrointestinal diseases, such as irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD) or peptic ulcer disease. In addition, circadian disruption accelerates aging, and promotes tumorigenesis in the liver and GIT. Identification of the molecular basis and role of melatonin in the regulation of circadian rhythm allows researchers and clinicians to approach gastrointestinal diseases from a chronobiological perspective. Clinical studies have demonstrated that the administration of melatonin improves symptoms in patients with IBS and GERD. Moreover, our own studies indicate that melatonin significantly protects gastrointestinal mucosa, and has strong protective effects on the liver in patients with non-alcoholic steatohepatitis (NASH). Recently, it has been postulated that disruption of circadian regulation may lead to obesity by shifting food intake schedules. Future research should focus on the role of clock genes in the pathophysiology of the GIT and liver.
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PMID:Gut clock: implication of circadian rhythms in the gastrointestinal tract. 2167 61

Since 2005, every annual meeting of the Japanese Gastroenterological Association has included a core symposium for functional gastrointestinal disorders. At the 6th annual meeting, the core symposium was 'Pathophysiology and New Treatment'. At the 7th annual meeting, the core symposium was 'Pathophysiology and Motility'. This review summarizes the papers presented at these meetings. At the 6th meeting, we recognized that Japanese researchers successfully produced and developed many agents that are safe and effective for the treatment of functional gastrointestinal disorders, such as 5-hydroxytryptamine receptor-associated compounds, lubiprostone, Japanese herbal medicine, and other drugs. Data were validated from a clinical as well as an experimental viewpoint. Findings included the effects of sumatriptan and nizatidine, acylated or des-acylated ghrelin, T-cell-activating anti-CD3 antibody, and transient receptor potential vanilloid-1. At the 7th meeting, not only functional dyspepsia and irritable bowel syndrome (IBS), but also non-erosive esophageal reflux disease (NERD) and chronic intestinal pseudo-obstruction were actively discussed from a motility viewpoint, including papers about sham feeding and gastric motility, genetic polymorphism and motility, the role of transient receptor potential A1 on gastric accommodation, esophageal motility and NERD, diagnosis and treatment of chronic intestinal pseudo-obstruction, immunological basis of motility in IBS, developing non-invasive colonic function test, and fecal distribution in IBS patients.
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PMID:Management and pathophysiology of functional gastrointestinal disorders. 2226 84

Ghrelin is a 28-amino-acid peptide that plays multiple roles in humans and other mammals. The functions of ghrelin include food intake regulation, gastrointestinal (GI) motility, and acid secretion by the GI tract. Many GI disorders involving infection, inflammation, and malignancy are also correlated with altered ghrelin production and secretion. Although suppressed ghrelin responses have already been observed in various GI disorders, such as chronic gastritis, Helicobacter pylori infection, irritable bowel syndrome, functional dyspepsia, and cachexia, elevated ghrelin responses have also been reported in celiac disease and inflammatory bowel disease. Moreover, we recently reported that decreased fasting and postprandial ghrelin levels were observed in female patients with functional dyspepsia compared with healthy subjects. These alterations of ghrelin responses were significantly correlated with meal-related symptoms (bloating and early satiation) in female functional dyspepsia patients. We therefore support the notion that abnormal ghrelin responses may play important roles in various GI disorders. Furthermore, human clinical trials and animal studies involving the administration of ghrelin or its receptor agonists have shown promising improvements in gastroparesis, anorexia, and cancer. This review summarizes the impact of ghrelin, its family of peptides, and its receptors on GI diseases and proposes ghrelin modulation as a potential therapy.
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PMID:Role of ghrelin in the pathophysiology of gastrointestinal disease. 2407 6

This article reviews the effectiveness of Kampo (traditional Japanese herbal medicine) in the treatment of functional gastrointestinal disorders, especially functional dyspepsia (FD) and irritable bowel syndrome (IBS). The results of four randomized, controlled trials (RCTs) suggested the usefulness of rikkunshito in relieving the subjective symptoms of patients with FD. Rikkunshito significantly improved not only gastric symptoms, such as epigastiric discomfort, but also extra-gastric symptoms, such as general fatigue, when compared with control drugs. The therapeutic effects of rikkunshito were more evident when it was prescribed to patients with "kyosho", i.e., low energy. Two RCTs suggested the efficacy of keishikashakuyakuto for IBS.Basic research studies have demonstrated that these Kampo medicines have multiple sites of action to improve subjective symptoms. For example, rikkunshito improves gastric motility dysfunction, including impaired adaptive relaxation and delayed gastric emptying, gastric hypersensitivity, and anorexia via facilitation of ghrelin secretion. It also exhibits anti-stress effects, i.e., it attenuates stress-induced exacerbation of gastric sensation and anorexia, as well as the hypothalamic-pituitary-adrenocortical axis and sympathetic activation. Keishikashakuyakuto exhibited not only an antispasmodic effect on intestinal smooth muscle, but also antidepressant-like effects. Case series suggest that other Kampo prescriptions are also effective for FD and IBS. However, further studies are necessary to evaluate their efficacy.
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PMID:Effects of Kampo on functional gastrointestinal disorders. 2444 39

Brain ghrelin plays a role in gastrointestinal functions. Among them, ghrelin acts centrally to stimulate gastrointestinal motility and induce visceral antinociception. Intestinal barrier function, one of important gastrointestinal functions, is also controlled by the central nervous system. Little is, however, known about a role of central ghrelin in regulation of intestinal permeability. The present study was performed to clarify whether brain ghrelin is also involved in regulation of intestinal barrier function and its mechanism. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Intracisternal injection of ghrelin dose-dependently abolished increased colonic permeability in response to LPS while intraperitoneal injection of ghrelin at the same dose or intracisternal injection of des-acyl-ghrelin failed to block it. Carbachol potently attenuated LPS-induced intestinal hyperpermeability, and atropine or bilateral subdiaphragmatic vagotomy prevented the improvement of intestinal hyperpermeability by central ghrelin. Intracisternal (D-Lys3)-GHRP-6, a selective ghrelin receptor antagonist, significantly blocked improvement of intestinal barrier function by intravenously administered 2-deoxy-d-glucose, central vagal stimulant. Intracisternal injection of orexin 1 receptor antagonist, SB-334867 blocked intracisternal ghrelin-induced improvement of colonic hyperpermeability. These results suggest that exogenously administered or endogenously released ghrelin acts centrally to improve a disturbed intestinal barrier function through orexinergic signaling and the vagal cholinergic pathway. Central ghrelin may be involved in the pathophysiology and be a novel therapeutic option in not only gastrointestinal diseases such as irritable bowel syndrome but also non-gastrointestinal diseases associated with the altered intestinal permeability.
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PMID:Ghrelin acts in the brain to block colonic hyperpermeability in response to lipopolysaccharide through the vagus nerve. 3244 42