Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotoninergic innervation may contribute to the control of colonic motility and to visceral sensation from the large bowel. Indeed, ondansetron hydrochloride, a selective 5-hydroxytryptamine type 3 receptor antagonist, has been shown to slow colonic transit in healthy volunteers. Thus, we wished to determine whether 5-hydroxytryptamine type 3 receptor blockade slows colonic and small bowel transit in patients with diarrhea-predominant irritable bowel syndrome (IBS) and whether symptoms would be ameliorated with drug therapy. Of 14 patients with well-established IBS who entered a randomized, double-blind, placebo-controlled crossover pilot trial of 4 weeks of treatment with ondansetron, 16 mg three times daily, 11 completed the study. A minimal "washout period" of 4 weeks (median, 7 weeks) separated the two phases of the trial because patients were required to have similar symptoms before both periods of the study. Colonic transit tended to be longer during drug therapy than during the placebo trial, but this difference was not significant. Small intestinal transit and orocecal transit were unchanged by the drug. The integrated and peak postprandial increases in neurotensin, peptide YY, and human pancreatic polypeptide in serum were not significantly different in the drug and placebo periods. After treatment with ondansetron, stool consistency improved significantly; however, stool frequency, stool weight, abdominal pain, and the symptom criteria for IBS were not significantly altered by the drug. The results of this pilot study suggest that the motor effects expected with 5-hydroxytryptamine type 3 receptor blockade (namely, slowed colonic transit) may be diminished in some patients with IBS. The subjective improvement in stool consistency may reflect changes in the perception of defecation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study. 143 22

Future treatments of functional intestinal disorders (FID) are essentially dependent on the possible pathophysiologic hypotheses. Schematically, symptoms experienced by patients with FID can be attributed to intestinal (small or large intestine) motor disturbances or to visceral sensitivity derangement, which, in turn, may be primary or secondary to an anomalous response to alimentation, liberation of hormones or neuromediators, or to a "stress" situation. New therapeutic agents can be directed against the symptoms experienced by patients (? action on pain or intestinal transit disorders) or against the initial pathophysiologic mechanisms. In the treatment of functional diarrhea, several substances have been proposed recently. Encephalines are peptides with extremely short duration of action which are degraded by two membranous enzymes, encephalinase and carboxypeptidase. Recently, it has been shown that acetorphan, an inhibitor of encephalinase, is efficacious in acute diarrhea. Alpha-2-antagonists are substances which are capable of slowing intestinal transit time and increasing intestinal absorption. Their antidiarrheic action is moderate, and they do not act on abdominal pain. Molecules that do not traverse the neuromeningeal barrier but that act selectively on the digestive tract and are better tolerated are expected. In patients complaining of severe idiopathic constipation substances capable of stimulating colonic motility are useful: substance P or neurotensin analogues might prove interesting. Antagonists of opium receptors such as Naloxone have proved efficacious in the treatment of certain cases of chronic idiopathic intestinal pseudo-obstructions or severe constipation. The development of orally active substances or with hepatic elimination are a prerequisite. Therapy based on well characterized pathophysiologic abnormalities would be welcome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapeutic perspectives in the irritable bowel syndrome]. 221 Jan 91

To determine if carbohydrates perfused into the ileum affect gastric emptying and circulating levels of gastrointestinal hormones, 18 healthy subjects were intubated with an oroileal tube. A 400-cal (60% carbohydrate, 20% protein, 20% fat) homogenized meal labeled with 111In-DTPA was then infused into the stomach over 10 min. Simultaneously, a test solution of normal saline (n = 6) or 12.5 (n = 4), 25 (n = 4), 50 (n = 2), or 100 (n = 2) mg/min of carbohydrates (75% rice starch, 25% glucose) containing a nonabsorbable marker, polyethylene glycol, was continuously perfused into the terminal ileum at 3 ml/min for 7 h. In one-half of the subjects the perfusate contained an amylase inhibitor (3.3 mg/ml) that reduced starch digestion and carbohydrate absorption. Gastric emptying was measured by a dual-headed gamma-camera. Plasma concentrations of hormones and the amount of carbohydrates passing the ileum were measured every 10 min. The amylase inhibitor significantly reduced the absorption of complex carbohydrates from the terminal ileum (p less than 0.05). Gastric emptying was significantly slowed by ileal perfusion of carbohydrates (p less than 0.01). This effect was enhanced by the amylase inhibitor (p = 0.06). Plasma concentrations of C-peptide, glucagon, motilin, gastrin, and human pancreatic polypeptide were not related to gastric emptying or ileal perfusates, but decreased concentrations of gastric inhibitory polypeptide and neurotensin and increased concentrations of peptide YY were significantly associated (p less than 0.05) with slowing of gastric emptying. Perfusing carbohydrates into the ileum was associated with nausea, abdominal pain, and vomiting, but we could detect no direct relationship between the onset of these symptoms and gastric emptying. Slowing of gastric emptying of a homogenized mixed meal by the entry of complex carbohydrates into the ileum may be partly mediated by peptide YY or nonvagally mediated neural mechanisms.
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PMID:Effect of ileal perfusion of carbohydrates and amylase inhibitor on gastrointestinal hormones and emptying. 246 4

We have reviewed data pertinent to three tumor syndromes that derive from overproduction of three GEP peptide hormones. The clinical syndrome of somatostatin excess remains well defined with diabetes, diarrhea, steatorrhea being predominant features. With the availability of assays and increasing awareness, more cases are being diagnosed in the intestine and these differ somewhat in their presentation with cholecystitis, GI bleeding, or a mass as the cardinal features. An unusual association with MEN II pheochromacytoma and neurofibromatosis is emerging. PPomas remain enigmatic. Although diarrhea is a feature, these tumors are usually silent and present with hypatomegally, abdominal pain, and jaundice because of the large size and malignant nature. Neurotensinomas remain rare and truly difficult to separate from the symptom complex produced by VIP excess. Edema, hypotension, cyanosis and flushing should alert one to the possibility of a neurotensin-secreting tumor.
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PMID:Somatostatinomas, PPomas, neurotensinomas. 282 62

26 children were investigated on an average 11.5 years after partial (n = 13) and total (n = 13) colonic resection. Total colectomy was followed by an increased frequency of gastrointestinal symptoms such as recurrent abdominal pain, flatulence, attacks of diarrhoea, frequent and pasty or liquid stools with strange smell. An increased salt or fluid intake was observed in one half of these patients. Their height and bone age was slightly but significantly reduced. Laboratory investigations revealed no significant deficiencies of electrolyts, vitamins or trace elements. However Renin (mean and 2s-range = 5.2; 2.7-6.8 ng/ml.h, normal values (NV) 1.3; 0.5-4.0 ng/ml.h, p less than 0.02), aldosterone (242.1; 168.4-357.8 pg/ml, NV 78.9; 39.4-168.4 pg/ml, *p less than 0.02), conjugated bile acids (11.3; 5.2-20.0 mumol/1, NV 4.2; 1.5-7.0 mumol/1, p less than 0.01) and serum urea concentration (32.5; 20.8-48.7 mg/dl, NV 14.6; 6.0-22.5 mg/dl, p less than 0.01) were significantly elevated. Three postprandial plasma levels of gastrin, VIP and neurotensin were within normal limits. In patients with partial large bowel resection all signs were less pronounced. According to our results a special diet in children years after colectomy seems not to be required.
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PMID:[Late results following partial and total colectomy in infancy]. 328 87

In 16 consecutive patients with systemic mastocytosis, we prospectively evaluated a variety of gastrointestinal functions and examined how they relate to the occurrence of gastrointestinal symptoms. Nine patients had either a duodenal ulcer or duodenitis. Hypersecretion of gastric acid was present in 6 patients, and in these patients the mean basal acid output was 20.7 +/- 4.1 mEq/h (range 14-39 mEq/h). Impaired small intestinal absorption occurred in 5 patients, although this was usually mild. The mean fractional emptying rate of liquids for all patients (14.7% +/- 2.3% per minute) did not differ from that for controls (10.7% +/- 0.6% per minute). Mean mouth-to-cecum transit time measured by breath hydrogen testing was the same among patients (87.7 +/- 6.7 min) and controls (86.7 +/- 8.0 min). Plasma histamine concentrations were increased in all patients (mean 1886 pg/ml, range 480-7450) and correlated with the basal acid output (r = 0.64, p less than 0.02) but not maximal acid output or the presence or absence of pain or diarrhea. Mean fasting plasma concentrations of motilin, substance P, and neurotensin from 6 patients did not differ significantly from controls, whereas gastrin and vasoactive intestinal peptide were significantly less than in controls (p less than 0.01). Gastrointestinal symptoms, consisting of abdominal pain or diarrhea, occurred in 80% of patients. Abdominal pain classified as dyspeptic was usually associated with acid-peptic disease of the duodenum and hypersecretion of gastric acid, whereas abdominal pain of a nondyspeptic character was not. Only in those cases of diarrhea consisting of greater than 200 g stool/day was gastric acid hypersecretion frequently found. Neither fecal urgency nor nondyspeptic pain could be accounted for by alterations of gastrointestinal transit. These results demonstrate that gastrointestinal symptoms, peptic disease, and mild malabsorption are much more common than described previously in patients with systemic mastocytosis. Furthermore, the results provide no evidence for the contention that altered gastrointestinal transit is involved in the pathogenesis of these symptoms.
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PMID:Gastrointestinal dysfunction in systemic mastocytosis. A prospective study. 339 14

Neurotensin is a 13-amino acid hormonal peptide, localized to specific areas in both the brain and gastrointestinal tract of many mammalian species. It has been described as causing a wide variety of central and peripheral actions. At present there is almost no information concerning the possible physiological and pathophysiological significance of this peptide especially in childhood. Therefore we investigated plasma concentrations of neurotensin-like immunoreactivity in 113 healthy and 103 children suffering from various gastrointestinal diseases. The fasting levels (48.7 +/- 17.4 pg/ml) were slightly lower (p less than 0.05) than our postprandial concentrations (72.9 +/- 28.1 pg/ml) 2-3 hours after breakfast. There was no age distribution. Significantly elevated levels were found in CF-patients (185.4 +/- 96.1 pg/ml; p less than 0.0001) and three children with active coeliac disease (252.3 pg/ml), whereas patients with Crohn's disease, ulcerative colitis and abdominal pain had normal values. Children after large bowel resection showed elevated plasma levels of neurotensin-like immunoreactivity (87.3 +/- 36.4 pg/ml), however, the differences were not significant.
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PMID:[Immunoreactive neurotensin in children with gastrointestinal diseases]. 370 82

A woman had episodic attacks of flushing associated with severe skin, bone, and abdominal pain, accompanied by mood alterations and anxiety, and followed by an organic psychosis. These symptoms and signs could be induced by small doses of clonidine, L-5-hydroxytryptophan, pentagastrin, insulin, epinephrine, compound 48/80, methacholine, morphine, histamine, or d-tubocurarine. Skin testing showed abnormally sensitive mast cells and an exaggerated axon flare. Cimetidine initially prevented the attacks but became less effective after 18 months. Thyrotropin-releasing hormone stopped the skin pain whereas neurotensin reproduced the burning sensation in the skin without inducing the attack. Both the flush and the organic psychosis were reversed entirely by naloxone or naltrexone, and the hallucinosis could be reversed by vasodilators.
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PMID:A case of episodic flushing and organic psychosis: reversal by opiate antagonists. 618 3

Hepatic porphyrias are characterized by neurological symptoms manifested by abdominal pain, neuropathies and mental aberrations. Porphyrins are ubiquitous and essential biochemical constituents of living beings acting as mediators of oxidation reaction in the metabolism of the steroid, drugs, environmental chemicals or as a mean of exchanging gases, such as oxygen and carbon dioxide between the environment and the tissue of the body using endogenous polypeptide properties. The different porphyrins arising from the arrangement of normal heme synthesis are characterized by an accumulation and excretion of specific intermediate porphyrins and/or of precursors exerting toxic effect, initiating cascades of generations of polypeptides, neurotransmitters and gut-brain axis peptide responsible for the symptoms of clinical status. We studied polypeptide levels in 27 patients (19 females, 8 males) presenting acute attack of hepatic porphyria: 2 with ALA dehydratase-deficient porphyria; 9 with acute intermittent porphyria; 12 with porphyria cutanea tarda and 4 with variegate porphyria. During acute attacks of porphyria, polypeptides were found to be constantly increased: vasoactive intestinal polypeptide (VIP); neurotensin (NT); substance P; pancreatic polypeptide; gastrin-releasing peptide; gastrin and motilin. Administration of the somatostatin (antagonizing polypeptide), which was undetectable or low before treatment, apparently alleviated the acute symptomatology. Elevated levels of polypeptides, at least partly, contribute to appearance of acute symptoms in porphyria patients.
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PMID:Polypeptide levels increase during acute onset of hepatic porphyrias. 907 85

Estradiol, progesterone and some of their metabolites modulate the activity of neurotransmitters and neuropeptides in the CNS. The distribution and concentrations of sex steroids in the various CNS regions is partly dependent on the serum levels, but also on the local synthesis of the steroids. In general, estradiol and testosterone exert a stimulatory, progesterone an inhibitory effect on neuronal activities which are mediated by excitatory (e.g. glutamate, aspartate), and inhibitory amino acids (e.g. GABA) and neuropeptides (e.g. beta-endorphin), respectively. Gonadotropin release is primarily governed by the rhythm of pulsatile secretion of GnRH in the hypothalamus which is controlled by estradiol and progesterone by means of inhibitory or stimulatory modulation of the amplitude and frequency of GnRH pulses. The discharges of GnRH neurons triggered by excitatory amino acids are modulated by estradiol, while the inhibitory effect of progesterone is mediated by GABA and beta-endorphin which cause hyperpolarization of the GnRH neurons and consequently a reduced pulse frequency. The pulse amplitudes are primarily influenced by estradiol, but neuropeptide Y, neurotensin and noradrenaline contribute to their preovulatory enhancement. The postovulatory rise in core temperature is caused by the increasing level of progesterone and its metabolite 3 alpha-pregnanolone, respectively. Despite of this, up to 20% of ovulatory cycles do not show any rise in body temperature. Although 3 alpha-pregnanolone has sedative activities, there is no change in sleep quality during the luteal phase due to their low serum levels. It could be demonstrated that performance on tests of articulatory and fine motor skills are enhanced in the late follicular phase as compared to the menstruation phase, while spatial ability was better during menses. Estrogens may influence mood and well-being in a favorable manner, while in predisposed women progesterone may cause symptoms of premenstrual syndrome. In most women there are, however, no cycle-dependent mood changes. An increase in appetite can be observed during the periovulatory phase and before menses, while sexual interest increases in the follicular phase. Somatic complaints (back pain, abdominal pain, breast tenderness) which are highest before and during menstruation, are probably associated with a lowered pain threshold due to a fall in the beta-endorphin levels in the CNS.
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PMID:[Influence of the ovarian cycle on the central nervous system]. 1201 35


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