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)

Somatostatin and octreotide have a definitive role in the management of symptomatic gut neuroendocrine tumours, particularly VIPomas and carcinoid. They probably also have a role in variceal bleeding, but this needs further confirmatory randomized trials. At present there is a potential role in the management of short bowel syndrome, dumping syndrome and gastrointestinal fistulae, but randomized clinical studies are needed. Possibly there is a role in AIDS-related diarrhoea and 'idiopathic' secretory diarrhoea, but more evidence is required. They have no role in acute pancreatitis and peptic ulcer bleeding. Irritable bowel syndrome remains unexplored but unlikely to benefit.
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PMID:Somatostatin and octreotide in gastroenterology. 168 74

The description of a patient with the irritable bowel syndrome whose symptoms were completely relieved by the administration of somatostatin raised the possibility that a deficiency of somatostatin may be involved in the pathogenesis of the disorder. We have examined this possibility by studying 11 healthy controls (35 +/- 12 years; mean +/- S.D. 8 female) and 10 irritable bowel syndrome patients (39 +/- 14 years; 7 female) complaining of frequency of defaecation of 4 or more times a day. Plasma somatostatin concentrations were determined by specific radioimmunoassay, fasting and at 15, 30, 45, 60, 90, 120 and 180 min after a standard breakfast. Irritable bowel syndrome patients and controls had similar fasting (27.4 +/- 5.1 vs. 35.2 +/- 4.3 pg/ml; mean +/- S.E.M. and integrated increment of post-prandial (5105 +/- 858 vs. 3885 +/- 793 pg.min/L) plasma concentrations of somatostatin, as assessed by student's t-test. These observations do not support the idea that a state of somatostatin deficiency exists in the irritable bowel syndrome.
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PMID:Short report: plasma somatostatin concentrations in the irritable bowel syndrome. 168 24

The author gives an account of clinical syndromes which develop as a result of overproduction of gastrointestinal hormones. From the various diagnostic approaches, which are not always available or are expensive, the author summarizes the importance of thin-needle biopsy under sonographic control, the argentaffine technique (Grimelius) and histoenzymatic examination for neuron specific enolase. In addition to surgical treatment treatment with streptozotocine, 5-FU, dimethyl triazenoimidazole carboxamide and somatostatin is possible. The author draws attention to the possibility of using somatostatin not only in the treatment of apudomas but also of haemorrhage into the gastrointestinal tract and in the treatment of fistulae. Neuroendocrine factors probably play a significant role in the pathophysiology of irritable colon, Crohn's disease, achalasia and Hirschsprung's disease.
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PMID:[Gastrointestinal hormones--clinical significance]. 273 95

The main source of circulating immunoreactive somatostatin (IRS) seems to be the gastrointestinal tract. We therefore investigated plasma IRS in patients with various gastrointestinal diseases. Mean basal IRS oscillated between 46 and 73 pg/ml. A postprandial rise was observed in all patients and age-matched controls. However, the increment was significantly higher in patients with duodenal ulcer (159 +/- 20 pg/ml), active ulcerative colitis (176 +/- 17 pg/ml), and irritable bowel syndrome (194.4 +/- 20.4 pg/ml). Patients with duodenal ulcers who underwent vagotomy showed a decreased postprandial increment (107 +/- 10 pg/ml) when compared with active duodenal ulcer patients. No difference was demonstrable between controls and individuals with gastric ulcer, and patients with inactive ulcerative colitis. These results suggest that vagal innervation plays a role in postprandial IRS stimulation, whereas gastric hyperacidity, acute lesions of the colonic mucosa, and hypermotility of the gastrointestinal tract are associated with an exaggerated postprandial IRS response. Since somatostatin is known to influence many gastrointestinal functions, these variations in circulating IRS concentrations may be of pathophysiologic importance.
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PMID:Circulating immunoreactive somatostatin in gastrointestinal diseases. Decrease after vagotomy and enhancement in active ulcerative colitis, irritable bowel syndrome, and duodenal ulcer. 289 Nov 85

The mucosal concentrations of seven regulatory peptides and the density properties and integrity of their storage granules have been studied in mucosal biopsies from the human jejunum in eight gastrointestinal disease states and compared with normal controls. In diseases with associated mucosal inflammation (coeliac disease, Crohn's disease with jejunal involvement, postinfective tropical malabsorption, and common variable immunodeficiency) there was a selective increase in fragility of the gastric inhibitory polypeptide (GIP) and somatostatin storage granules. The gastrin, motilin, enteroglucagon, secretin, and vasoactive intestinal polypeptide granules had normal properties in these conditions. In diseases in which diarrhoea occurred in the absence of changes in jejunal mucosal histology (irritable bowel syndrome, pancreatic insufficiency, jejuno-ileal bypass for morbid obesity, and purgative abuse) there were no abnormalities of the storage granules. Increased mucosal concentrations of all peptides except vasoactive intestinal polypeptide (VIP) were found in coeliac disease and selective increases of VIP found in Crohn's disease, motilin in the irritable bowel syndrome and gastrin and GIP in pancreatic insufficiency. It is suggested that the storage granule abnormalities in the diseases with abnormal mucosal histology are secondary to the inflammatory changes.
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PMID:Gastrointestinal regulatory peptide storage granule abnormalities in jejunal mucosal diseases. 614 62

Autoantibodies reacting with endocrine cells in the gastrointestinal mucosa were found by indirect immunofluorescence in 22 out of 268 sera (8.2%) obtained from patients with coeliac disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, and from subjects without bowel disease. A double immunofluorescence technique showed that the autoantibodies reacted with cells secreting gastric inhibitory polypeptide (glucose dependent insulinotropic polypeptide, GIP), secretin, somatostatin or enteroglucagon. Most sera contained antibodies against more than one cell type. Neither the presence of a particular antibody nor the pattern of antibody combinations appeared to be specific for any diagnostic category. The mean plasma GIP concentrations, however, both fasting and two hours after a test meal, were significantly lower in subjects with GIP cell autoantibodies. Thus gut hormone cell autoantibodies may be markers of impaired hormone secretion.
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PMID:Autoantibodies to gut hormone secreting cells as markers of peptide deficiency. 634 Nov 78

Irritable bowel syndrome (IBS) patients exhibit enhanced sensitivity to rectal distention. The somatostatin analog reduces perception of rectal distention in healthy volunteers without modifying rectal resistance. We evaluated whether octreotide has similar effects on rectal perception and resistance in diarrhea-prone IBS patients. Octreotide (100 micrograms s.c.) and placebo were injected in double-blind fashion in eight IBS patients. Rectal balloons measured volumes that evoked increasing levels of perception and intrarectal pressures. After placebo, threshold perception, pressure, urgency and maximal tolerated volume were reported at 18 +/- 5, 46 +/- 8, 72 +/- 7 and 102 +/- 10 ml by the IBS patients, values less than we have observed in healthy volunteers. With octreotide, these sensations were perceived at higher volumes (40 +/- 10, 89 +/- 16, 167 +/- 20 and 202 +/- 25 ml, P < .05) that approximated responses in healthy volunteers. IBS patients exhibited higher rectal pressures at each volume and showed a trend to higher rectal resistance (0.13 +/- 0.02 mmHg/ml) than we have observed in healthy volunteers. These abnormalities were normalized by octreotide. Octreotide did not block the rectoanal inhibitory reflex confirming a lack of effect on local rectal reflex arcs. As with healthy volunteers, IBS patients with diarrhea experience reduced perception of rectal distention after octreotide. Octreotide also reduces elevated rectal pressures in IBS patients, in contrast to healthy volunteers. Thus, octreotide shows potential therapeutic benefit in IBS via dual effects on visceral afferent pathways and rectal wall stiffness.
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PMID:Somatostatin analog inhibits afferent response to rectal distention in diarrhea-predominant irritable bowel patients. 813 33

The potential therapeutic applications of somatostatin and octreotide in gastroenterology involve gut neuro-endocrine tumours, bleeding varices, bleeding peptic ulcers, gastro-intestinal fistulae, pancreatic fistulae, dumping syndrome, pancreatic pseudocysts, short bowel syndrome, acute pancreatitis, AIDS-related diarrhoea, intestinal subacute obstruction, idiopathic 'diarrhoea', irritable bowel syndrome and GIT tumours. Octreotide has a longer duration of action than somatostatin and can be administered by subcutaneous injection, thus making it suitable for long-term administration. Many of the potential gastro-intestinal indications require long-term administration and thus octreotide would be the agent of choice.
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PMID:Potential indications for octreotide in gastroenterology: summary of workshop. 835 70

Over the last decade, the role of visceral sensitivity has been largely recognized in the pathophysiology of functional digestive disorders, particularly in the irritable bowel syndrome. These studies have highlighted the role of afferent pathways arising from the gut as a possible target for new treatments intended to relieve pain or modify altered reflexes present in such patients. These pharmacological targets have been identified mainly by studies on animal models of visceral hyperalgesia of various origins including local inflammation. Locally, several mediators are of paramount importance for sensitization of nerve endings: 5-hydroxytryptamine, bradykinin, tachykinins, calcitonin gene-related peptide, and neurotrophins. Selective antagonists to various subtypes of their receptors are currently available and have been shown to be active in these animal models. Other substances, such as somatostatin, opiold peptides, cholecystokinin, oxytocin, and adenosine, modulate the transmission of nociceptive inputs from the gut to the brain and are of clinical interest. This article reviews the current understanding of these mediators. Although these agents seem to be promising tools for the treatment of visceral hyperalgesia and its consequences (abdominal pain and disturbed reflexes), their clinical efficacy remains to be shown. A better understanding of the nature and the location of the defect in the sensory pathways may permit the selection of subgroups of patients for treatment according to the pharmacological properties of these new therapeutic agents.
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PMID:Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. 913 53

Octreotide, the long-acting somatostatin analogue, has been reported to modulate gastrointestinal motility in both animals and humans. A role in colonic peristalsis and a possible clinical application in common disorders, such as chronic constipation and irritable bowel syndrome, have not been evaluated. It has been previously suggested that octreotide promotes the descending relaxation of the peristaltic reflex arc. We hypothesized that this effect may involve inhibition of the motility index (MI) of the distal colon. To test this proposal, we studied peristalsis in isolated rabbit colons and also in the intact distal colons of anesthetized rabbits undergoing octreotide administration. Left colons of New Zealand white rabbits were harvested, placed in an isolated organ chamber and perfused with Krebs-Ringer bicarbonate solution via the inferior mesenteric artery. In a separate preparation, the colons were left in situ. Motility was quantified with a 6-port continuous infusion manometry catheter. The MI (mm Hg/min) was calculated by integration of the area of the digitalized signal (8/s), which reflected high-pressure peaks of different magnitudes. High-pressure waves were defined as > 20 mm Hg. Octreotide was infused via the inferior mesenteric artery in the isolated specimen or the lateral ear vein in the anesthetized animals in concentrations of 10(-12) to 10(-6) M. Octreotide inhibited high-pressure waves in a dose-dependent manner. These effects resulted in a decreased MI, with the maximum inhibition of 24.6% at 10(-11) M (p < 0.05 by ANOVA). At that concentration, the number of peaks > 20 mm Hg were reduced by 62.2%. The data indicate that octreotide decreases the MI by inhibition of high-pressure waves in the distal rabbit colon. These findings are consistent with the proposal that somatostatin may augment descending relaxation of the peristaltic reflex arc. This effect is independent of neural modulation.
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PMID:Octreotide acetate inhibits motility in the rabbit distal colon. 925 4


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