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)

Since prostaglandins (PGs) appear to be important in the pathogenesis of secretory diarrhoea, a radioimmunoassay for determination of PGE2 was applied to purified samples of jejunal fluids aspirated at the ligament of Treitz. Studies on validation of the assay system included quantification of PGE2 following alkali-treatment of the samples, variation of the sample volume, and fractionation of immunoreactive- and tracer PGE2. In addition, the specificity of the assay system was confirmed by gas chromatography--mass spectrometry. In healthy volunteers (n = 22) the PGE2 concentration range was 5--205 pg/ml (99% confidence limits). Alcohol addicts (n = 27) with diarrhoea or steatorrhoea had PGE2 levels within the normal range. Values beyond the 99% upper confidence limit were observed in ten out of seventeen patients with chronic diarrhoea (205--340 pg/ml) and two out of fifteen patients with intermittent diarrhoea (265 and 275 pg/ml) classified as irritable bowel syndrome. In six patients with high PGE2 concentrations indomethacin treatment (25 mg x 4 daily) halved the associated diarrhoea and reduced PGE2 concentrations to normal levels. Subsequently, a double-blind multiple randomized clinical trial was carried out in two single patients. Indomethacin proved to be effective in preventing diarrhoea only in the patient with a raised PGE2 level (P less than 0.005).
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PMID:Prostaglandin E2 in jejunal fluids and its potential diagnostic value for selecting patients with indomethacin-sensitive diarrhoea. 679 38

In some emergency situations of colo-rectal pathology, especially those characterized by hemorrhaging, the endoscopy has acquired, with the passing of years, a fundamental role both from the diagnostic and the therapeutic point of view. In no more than 25% of the lower intestinal tract hemorrhages, the clinical picture does have the signs of an emergency. The diverticula, IBD and angiodysplasias are primarily responsible for rendering these characteristics. Even when possible problems concerning an accurate intestinal cleaning can arise, a correct diagnosis is possible at least in seven cases out ten. When the colonoscopy isn't conclusive and the bleeding persists may be recommended the selective arteriography (helpful also in hemorrhages lower than 0.5 ml/min). Also in cases of acute obstructive syndrome the colonoscopy, taking advantage of the direct view of the lesion, can give a correct diagnosis, sometimes supported by the histologic examination. Regarding the operating capacity of the method, the endoscopy can resolve minute and localized bleeding lesions. The Argon or Nd:YAG laser photocoagulation is widely used. Recently BICAP and heater probe methods have been developed, which aveld the problem connected to the HF electrocoagulation. A very efficacious and simple method is that of injecting 1:10.000 adrenalin, 1% polidocanol, absolute ethanol or hypertonic solution around the lesion. The scarred strictures are those more easily and safely treated by pneumatic dilatation or (limited to the rectum-sigmoid) by Savary sounds. In the volvulus or bowel invagination, just by having the endoscope goes up in the lumen, often normal condition settles again. In the Ogilvie's syndrome you can deflate the cecum with an aspirator or more simply by positioning a tube above the hepatic flexure, with 85% success. In the malignant strictures the debulking of tumor mass by laser treatment, sometimes followed by dilatation, may be preparatory to the surgery or purely palliative. Finally the extraction of foreign bodies must be performed, in order to obtain a relaxed anal sphincter, in general anaesthesia or by a previous rigid rectoscope dilatation.
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PMID:[Emergencies in colorectal diseases: role of the endoscopist]. 892 30

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.
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PMID:Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. 911 22

It has been suggested that the symptoms of irritable bowel syndrome (IBS) may be wrongly attributed to lactose intolerance. We examined the relations among IBS, demographic factors, living habits, and lactose intolerance. On the basis of a lactose tolerance test with ethanol, 101 of the 427 healthy subjects studied were lactose maldigesters and 326 were lactose digesters. IBS was diagnosed by means of the Bowel Disease Questionnaire, according to the Rome criteria. The use of dairy products and symptoms experienced after their consumption were recorded. IBS was found in 15% of both the lactose maldigesters and lactose digesters. One-third of the subjects reported intolerance to dairy products containing < or = 20 g lactose. About half of this third were lactose maldigesters and about half were lactose digesters. As explanations for this subjective lactose intolerance, the logistic regression model estimated lactose maldigestion (odds ratio: 10.3; 95% CI: 5.2, 20.4), IBS (4.6; 2.1, 10.1), experience of symptoms other than gastrointestinal ones (2.3; 1.2, 4.5), and female sex (2.1; 1.1, 4.0). Characteristics common to both subjective lactose intolerance and IBS were female sex and the experience of abdominal pain in childhood (P < 0.01). Age, regularity of meals, and the amount of physical activity were not associated with either subjective lactose intolerance or IBS. Of the subjects with IBS, the percentage of lactose maldigesters was the same as in the whole study group (24%) but the number who reported lactose intolerance was higher (60% compared with 27%, P < 0.001). We showed a strong relation among subjective lactose intolerance, IBS, the experience of abdominal pain in childhood, and female sex.
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PMID:Role of irritable bowel syndrome in subjective lactose intolerance. 953 18

Calcium ions play an important role in the normal functioning of the gastrointestinal system. The calcium channel blockers appear to affect all the organs of the gastrointestinal tract and may have therapeutic efficacy on esophageal spasm, irritable bowel syndrome, mesenteric vascular insufficiency, dyskinesis of the Sphincter of Oddi, and insulinoma. Adverse effects are limited predominantly to constipation and some aggravation of ethanol-induced ulcer disease. In addition, the drugs continue to serve as important biologic probes for understanding the normal and abnormal functioning of the gastrointestinal tract.
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PMID:Calcium Channel Blockers and the Gastrointestinal Tract. 1186 76

There is mounting evidence that the vanilloid (capsaicin) receptor; transient receptor potential channel, vanilloid subfamily member 1 (TRPV1), is subjected to multiple interacting levels of control. The first level is by reversible phosphorylation catalyzed by intrinsic kinases (e.g. protein kinase A and C) and phosphatases (e.g. calcineurin), which plays a pivotal role in receptor sensitization vs. tachyphylaxis. In addition, this mechanism links TRPV1 to intracellular signaling by various important endogenous as well as exogenous substances such as bradykinin, ethanol, nicotin and insulin. It is not clear, however, whether phosphorylation per se is sufficient to liberate TRPV1 under the inhibitory control of phosphatydylinositol-4,5-bisphosphate. The second level of control is by forming TRPV1 heteromers and their association with putative regulatory proteins. The next level of regulation is by subcellular compartmentalization. The membrane form of TRPV1 functions as a nonselective cation channel. On the endoplasmic reticulum, TRPV1 is present in two differentially regulated forms, one of which is inositol triphosphate-dependent whereas the other is not. These three TRPV1 compartments provide a versatile regulation of intracellular Ca(2+) levels. Last, there is a complex and poorly understood regulation of TRPV1 activity via control of gene expression. Factors that downregulate TRPV1 expression include vanilloid treatment and growth factor (notably, nerve growth factor) deprivation. By contrast, TRPV1 appears to be upregulated during inflammatory conditions. Interestingly, following experimental nerve injury and in animal models of diabetic neuropathy TRPV1 is present on neurons that do not normally express TRPV1. Combined, these findings imply an important role for aberrant TRPV1 expression in the development of neuropathic pain and hyperalgesia. In humans, disease-related changes in TRPV1 expression have already been described (e.g. inflammatory bowel disease and irritable bowel syndrome). The mechanisms that regulate TRPV1 gene expression under pathological conditions are unknown but a better understanding of these pathways has obvious implications for rational drug development.
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PMID:Biochemical pharmacology of the vanilloid receptor TRPV1. An update. 1512 91

Spinal cord stimulation (SCS) has been found to relieve neuropathic and ischemic pain clinically and to attenuate a nociceptive reflex in an animal model of acute colonic hypersensitivity. The goal of the present study was to determine the effect of SCS in a rat model of post-inflammatory colonic hypersensitivity. Acute inflammation was induced in rats by a single enema of trinitrobenzenesulfonic acid (TNBS) (50 mg/kg, 0.5 ml, 25% EtOH). Control rats received a single saline enema. A visceromotor behavioral response (VMR), induced by innocuous colorectal distention (30 mm Hg, 10 min) was used to quantify the level of colonic sensitivity on day 3 and 30 post-enema. Prior to VMR testing, under general anesthesia, an electrode (cathode) was placed epidurally on the dorsal surface of the spinal cord at L1 with a paravertebral anode plate. Three to 7 days after implantation of the SCS electrode, the effect of SCS (50 Hz, 0.2 ms, amplitude 90% of motor threshold for 30 min) on colonic sensitivity was determined. On day 30, rats that had received a single TNBS enema were hypersensitive to innocuous colonic distention when compared to rats that received a saline enema (VMR/10 min: TNBS: 17.2+/-0.8 vs. Saline: 9.6+/-1.1, p<0.01). Spinal cord stimulation significantly reduced the VMR in the TNBS-enema group to a value that resembled the saline-enema group (VMR/10 min: TNBS: 11.2+/-1.2 vs. Saline: 10.0+/-1.0). This study provides the first evidence that SCS might be a potential therapeutic for the treatment of abdominal pain observed in patients with post-inflammatory irritable bowel syndrome.
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PMID:Spinal cord stimulation attenuates visceromotor reflexes in a rat model of post-inflammatory colonic hypersensitivity. 1618 12

Transient inflammation is known to alter visceral sensory function and frequently precede the onset of symptoms in a subgroup of patients with irritable bowel syndrome (IBS). Duration and severity of the initial inflammatory stimulus appear to be risk factors for the manifestation of symptoms. Therefore, we aimed to characterize dose-dependent effects of trinitrobenzenesulfonic acid (TNBS)/ethanol on: (1) colonic mucosa, (2) cytokine release and (3) visceral sensory function in a rat model. Acute inflammation was induced in male Lewis rats by single administration of various doses of TNBS/ethanol (total of 0.8, 0.4 or 0.2 ml) in test animals or saline in controls. Assessment of visceromotor response (VMR) to colorectal distensions, histological evaluation of severity of inflammation, and measurement of pro-inflammatory cytokine levels (IL-2, IL-6) using enzyme-linked immunosorbent assay (ELISA) were performed 2h and 3, 14, 28, 31 and 42 days after induction. Increased serum IL-2 and IL-6 levels were evident prior to mucosal lesions 2h after induction of colitis and persist up to 14 days (p<0.05 vs. saline), although no histological signs of inflammation were detected at 14 days. In the acute phase, VMR was only significantly increased after 0.8 ml and 0.4 ml TNBS/ethanol (p<0.05 vs. saline). After 28 days, distension-evoked responses were persistently elevated (p<0.05 vs. saline) in 0.8 and 0.4 ml TNBS/ethanol-treated rats. In 0.2 ml TNBS/ethanol group, VMR was only enhanced after repeated visceral stimulation. Visceral hyperalgesia occurs after a transient colitis. However, even a mild acute but asymptomatic colitis can induce long-lasting visceral hyperalgesia in the presence of additional stimuli.
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PMID:Severity of mucosal inflammation as a predictor for alterations of visceral sensory function in a rat model. 1663 Jun 96

The role of alcohol use in irritable bowel syndrome (IBS) and dyspepsia is not well understood. We hypothesised that people with psychological distress who drink no alcohol, or excess alcohol, are at increased risk of having IBS or dyspepsia. Valid gastrointestinal (GI) symptom surveys were mailed to randomly selected cohorts of community residents. Associations between IBS, dyspepsia and abdominal pain and alcohol use were assessed using logistic regression adjusted for a Somatic Symptom Checklist score (SSC). A total of 4390 (80%) responded; of these, 10.5% reported IBS, 2% dyspepsia and 22% abdominal pain. Alcohol consumption >7 drinks week(-1) was associated with a greater odds for dyspepsia (OR 2.3; 95% CI:1.1-5.0) and frequent abdominal pain (OR 1.5; 95% CI: 1.1-2.0) but not IBS. However, significant interactions among gender, alcohol use and SSC scores were detected (P < 0.005). In females with a low SSC score, consuming alcohol > or =7 drinks week(-1) increased the odds of IBS compared to drinking alcohol moderately. Alcohol consumption was associated with dyspepsia and abdominal pain. A relationship with IBS was identified when interactions with somatization and gender were appropriately considered. Whether these associations are due to the effects of alcohol on the gut, or a common central mechanism remains to be determined.
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PMID:Influence of alcohol consumption on IBS and dyspepsia. 1704 Apr 11

Visceral organ "cross talk" is suspected to contribute to multiorgan symptomatology found in conditions such as irritable bowel syndrome and interstitial cystitis. The goal of the present study was to investigate the short- and long-term effects of acute colitis on bladder detrusor muscle contractility. We hypothesized that inflammation of the colon leads to changes in bladder function via direct changes in detrusor smooth muscle contractility. In this study, colonic inflammation was induced in male rats via an enema of trinitrobenzenesulfonic acid (TNBS) (50 mg/kg, 0.5 ml, 25% ethanol). Colitis was confirmed using gross morphology, histology, and measurements of myeloperoxidase activity. Saline enema-treated rats served as controls. Three, 15, and 30 days postenema treatment, bladder detrusor muscle contractility was investigated in response to electrical field stimulation (EFS), cholinergic agonism with carbachol (CCh), and KCl. During active colonic inflammation (day 3 post-TNBS enema), the bladder detrusor muscle appeared normal and showed no significant inflammation. However, abnormalities in bladder detrusor muscle contractility occurred in response to EFS and CCh but not KCl. During and after recovery from colonic inflammation (days 15 and 30 post-TNBS enema), changes in bladder detrusor muscle contractility in response to EFS and CCh returned to control levels. We found that a transient colonic inflammatory insult significantly attenuates the amplitude of bladder detrusor muscle contractions in vitro, at least in part, through changes in cholinergic innervation, which are reversible after recovery from the colitis.
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PMID:Changes in urinary bladder smooth muscle function in response to colonic inflammation. 1771 61


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