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 function of serotonin (5-HT)3 receptors on colonic transit was investigated in unanesthetized rats. The colonic transit was accelerated by 5-HT (10 mg/kg, s.c.), 2-methyl-5-HT (30 mg/kg, s.c.), neostigmine (0.03-0.1 mg/kg, s.c.), corticotropin releasing factor (CRF; 1 microgram intracerebroventricular administration) and restraint stress (for 45 minutes). A potent and selective 5-HT3 receptor antagonist, azasetron (+/-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro- 4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide monohydrochloride ; 0.01-10 mg/kg, p.o. inhibited the 5-HT-, CRF- and stress-accelerated colonic transit in a dose-dependent manner. Ondansetron (10 mg/kg, p.o.) and granisetron (1 mg/kg, p.o) also inhibited the stress-accelerated colonic transit, but azasetron was more effective than these two drugs. Atropine methylbromide (0.1 mg/kg, s.c.) and tetrodotoxin (0.01 mg/kg, s.c.) inhibited the accelerated colonic transit under stress conditions, but methysergide (10 mg/kg, s.c.), SDZ205-557 (10 mg/kg, s.c.), domperidone (30 mg/kg, p.o.), trimebutine (300 mg/kg, p.o.), did not. Azasetron (10 micrograms) administered intracerebroventricularly did not inhibit the stress-induced acceleration. These results suggest that endogenous 5-HT which is released through stress accelerates the colonic transit via the 5-HT3 receptors and finally a cholinergic mechanism. It is considered that azasetron inhibits colonic transit particularly under stress conditions through the blockade of the peripheral 5-HT3 receptors. Azasetron may improve bowel function in stress-related colonic dysfunction like irritable bowel syndrome.
Obes Res 1995 Dec
PMID:The function of 5-HT3 receptors on colonic transit in rats. 865 66

This multicenter, double-blind, placebo-controlled, parallel-group, randomized study assessed the efficacy, safety, and tolerability of a novel CCK-B antagonist CI-988 in the treatment of generalized anxiety disorder (GAD). Patients received placebo or CI-988 (300 mg/day, thrice daily) for 4 weeks. Patients with a primary diagnosis of GAD according to DSM-III-R criteria were randomized. The study design included a 1- to 2-week single-blind placebo baseline phase, followed by a 4-week double-blind treatment phase. Efficacy was measured weekly by Hamilton Rating Scale for Anxiety (HAM-A), Clinical Global Impressions of Severity and Change, UCLA-Multi Dimensional Anxiety Scale, and Hamilton Rating Scale for Depression. Patients were also evaluated to determine whether they met criteria for irritable bowel syndrome (IBS) at screening and were evaluated with a gastrointestinal visual analog scale at each visit. Eighty-eight patients were randomized to CI-988 (N = 45) and placebo (N = 43) at three centers. CI-988 did not demonstrate an anxiolytic effect superior to placebo in this clinical trial. There was no significant difference in mean change in HAM-A total between placebo (-7.73) and CI-988 (-8.64). However, a significant treatment-by-center interaction and a highly variable placebo response rate among the three centers limit the interpretation of the results. CI-988 did not have an effect on symptoms of IBS other than diarrhea, which worsened in patients with IBS. Other than a higher incidence of some gastrointestinal symptoms (diarrhea, dyspepsia, flatulence, and nausea), CI-988 was well tolerated. Results suggest that testing higher oral doses of CI-988 may be warranted.
J Clin Psychopharmacol 1995 Dec
PMID:A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder. 874 32

Intra-oesophageal balloon distension is a recognized stimulus for the assessment of oesophageal motor and sensory responses. It is increasingly being adopted by oesophageal laboratories, especially for the investigation of unexplained chest pain. The purpose of this paper is to review current knowledge concerning intra-oesophageal balloon distension. Perception of balloon distension is dependent upon demographic variables such as age, height and sex. Even when these are controlled for, patient groups are more sensitive to the stimulus than are healthy controls. This is true for patients with dysphagia and irritable bowel syndrome as well as those with unexplained chest pain. The role of intra-oesophageal balloon distension in determining oesophageal visceral hypersensitivity is outlined. In the investigation of unexplained chest pain, it may double the diagnostic yield of either acid perfusion or edrophonium provocation testing. Intra-oesophageal balloon distension has the potential to assess the response to therapy in patients with unexplained chest pain and has also been used in conjunction with cerebral evoked potential measurements to identify the afferent pathways involved. This technique provides another diagnostic tool that can readily be used in any oesophageal laboratory.
Eur J Gastroenterol Hepatol 1995 Dec
PMID:Intra-oesophageal balloon distension and oesophageal sensation in humans. 878 16

A pathogenic role for high numbers of bacteria in the small intestine had been suggested previously by bacterial counts on luminal aspirates, but these investigations were flawed by the sampling device "contamination" in the mouth and the changing nature of fluent intestinal content. A procedure was developed to sterilize the Watson biopsy capsule with HCl in the upper portion of the duodenum. Bacteria were counted in the mucosal homogenate of the first (diagnostic) duodenojejunal biopsy in 80 untreated celiac children, and in 46 children with irritable bowel syndrome (IBS) in a four-cell, controlled, randomized investigation. Persistence of bacteria on the mucosa for 20 h after the last meal was investigated in 62 subjects, and for 26 h after the last meal in 64 subjects. Bacteria, mainly streptococci and staphylococci, persisted at a concentration of 10(6) per gram of mucosa 20 h after the last meal. The number of bacteria per gram of mucosa was 24 times higher in all 62 children of the 20-h fast groups than in all 64 children of the 26-h fast groups (p < 0.001). The bacteria count in celiac children was 39 times higher in the 20-h fast group than in the 26-h one. This difference was significantly higher than the 11 times difference that was found on the normal mucosa between the 20- and 26-h fast IBS groups (p < 0.001), which was still significant. The number of bacteria on duodenojejunal mucosa depends on nutrient absorption and persists longer than the intermeal interval in these subjects.
Physiol Behav 1996 Dec
PMID:Microflora persistence on duodenojejunal flat or normal mucosa in time after a meal in children. 894 4

The possibility that 5-hydroxytryptamine (5-HT) acts as a key sensitising agent in the aetiology of irritable bowel syndrome (IBS) is reviewed. The strategic locations of 5-HT and its receptors are described, the most dominant being the 5-HT3 and 5-HT4 type. 5-HT, acting mostly at 5-HT3 or 5-HT3-like receptors, enhances the sensitivity of visceral neurones projecting between the gut and the central nervous systems. 5-HT, acting at 5-HT4 receptors promotes the sensitivity of enteric neurones that react to luminal stimuli. 5-HT4 and 5-HT3 receptors also mediate, respectively, sensitising and physiological actions of 5-HT on gastro-intestinal motor and secretory functions. This distribution implies that some 5-HT3 receptor antagonists might reduce certain symptoms of IBS, such as pain, by reducing the reactivity of the visceral afferent neurones linking the gut with the brain and spinal cord. However, such antagonists are not likely to find widespread clinical acceptance because they can also affect normal lower bowel function and promote constipation. 5-HT4 receptor antagonists, by contrast, reduce 5-HT-induced enteric nerve hypersensitivity without notably affecting the function of the normal bowel. Accordingly, these agents may reduce the symptoms of IBS directly, by reducing the incidence of defecation and diarrhoea and indirectly, by reducing both 'rebound' constipation and the post-prandial discomfort and pain associated with gastrointestinal hyper-reactivity.
Neurogastroenterol Motil 1996 Dec
PMID:5-Hydroxytryptamine and functional bowel disorders. 895 36

There is strong evidence that non-insulin-dependent-diabetes mellitus (NIDDM) has a polygenic mode of inheritance. Nevertheless, major gene effects may be involved in its pathogenesis, especially in forms with an early age of onset. We performed linkage analyses between 4 candidate genes for insulin resistance and NIDDM in a set of 55 multigenerational French Caucasian families, using the affected sib-pair approach. No significant results were obtained with glycogen synthase (GSY), insulin receptor substrate-1 (IRS-1) and apolipoprotein C-II (APOC-II) genes. However, a significant trend towards linkage was found between NIDDM and the phosphoenolpyruvate carboxykinase gene (PCK1) located on chromosome 20q (p = 0.005 for the mean estimated proportion of alleles shared identically by descent, mean IBD = 0.55), particularly among sib-pairs with diabetes diagnosed before the age of 46 years (p = 0.0003, mean IBD = 0.66). These results suggest that the PCK1 gene or a nearby locus contributes to the development of NIDDM in the French population.
Diabetes Metab 1996 Dec
PMID:Indication for genetic linkage of the phosphoenolpyruvate carboxykinase (PCK1) gene region on chromosome 20q to non-insulin-dependent diabetes mellitus. 898 54

Leukocyte scintigraphy (LS) was performed in 20 pediatric patients with inflammatory bowel disease (IBD: 10 with ulcerative colitis, 2 with indeterminate colitis, and 8 with Crohn disease) in different stages of clinical activity. Leukocytes were separated from 15 to 60 ml venous blood and were labeled in vitro with [99mTc]HM-PAO. The segmental extent (small intestine; ascending, transverse, and descending colon; and recto-sigmoideum) of the process was determined by LS. The uptake of each bowel segment was scored in relation to the bone marrow uptake. The scintigraphic activity, calculated by summing the segment scores, was compared with laboratory parameters. The mean labeling efficacy was 76% (60-86%). The segmental extent of the process determined by LS was compared with the results of barium enema or colonoscopy with regard to 32 bowel segments. The sensitivity, specificity, and accuracy of LS were 93, 88, and 91%, respectively. Two extraintestinal manifestations (abdominal abscess and joint involvement) were also detected by LS. These lesions were verified by computed tomography (CT) (abscess) and on the basis of the clinical outcome (arthritis). The scintigraphic activity correlated with the C-reactive protein (CRP) level (r = 0.82, p < 0.001), the alpha 2-globulin level (r = 0.63, p < 0.02), the sedimentation rate (r = 0.51, p < 0.05), and the fS iron level (r = -0.66, p < 0.005). LS is applicable in pediatric patients. The method is an excellent technique for assessment of the extent of IBD in children. Extraintestinal manifestations of IBD can also be investigated by LS. The scintigraphic activity is a useful parameter for determination of the activity of IBD in children.
J Pediatr Gastroenterol Nutr 1996 Dec
PMID:HM-PAO-labeled leukocyte scintigraphy in pediatric patients with inflammatory bowel disease. 898 43

The role of calcium in the etiology of anxiety has been proposed for several decades. Calcium channel blockers profoundly influence calcium metabolism and the transport of calcium. Even though the evidence for the role of calcium remains weak, drugs affecting calcium might be useful in the treatment of anxiety disorders. One of these compounds, verapamil, has been used to treat mood disorders. Calcium channel blockers have also been tried in other indications such as premenstrual syndrome, irritable bowel syndrome, schizophrenia, tardive dyskinesia, and Tourette's syndrome. However, the number of articles on the use of calcium channel blockers in the treatment of anxiety disorders is low. Three reports (two open, one double-blind) described some success in the treatment of panic disorder with verapamil, diltiazem, or nimodipine and one open-label study described unsuccessful treatment of anxiety and phobia with nifedipine in patients with various anxiety disorders. Further double-blind placebo-controlled studies of calcium channel blockers in the treatment of anxiety disorders are warranted to determine a possible role of these compounds in the armamentarium of antianxiety drugs.
Ann Clin Psychiatry 1996 Dec
PMID:Calcium channel blockers for anxiety disorders? 898 18

Subcutaneous administration of granisetron (BRL 43694, endo-1-methyl-N-(9-methyl-9-azabicyclo[3.3.1.]non-3-yl-1 H-indazole-3-carboxamide) and zacopride (4-amino-N-(1-azabicyclo[2.2.2.]oct-3-yl)-5-chloro-2-methoxybenzamide), two 5-HT3 receptor antagonists, at doses ranging from 3 to 1000 micrograms/kg, inhibited abdominal contractions induced by distension (30 mmHg, 10 min) of irritated colon (0.6% acetic acid) in conscious rats with a bell-shaped dose-response curve. The ED50 of granisetron and zacopride were 17.6 and 8.2 micrograms/kg, respectively. In contrast, both tropisetron (ICS 205-930, (3-a-tropanyl)t-indole-3-carboxylic ester) and ondansetron (GR38032F, 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1-yl)methyl]-4 H-carbazol-4-one hydrocloride dihydrate) were inactive in this model. These data further support the concept of a heterogeneity in the potency of 5-HT3 receptor antagonists in modulating visceral hypersensitivity in conscious rats. This finding is in agreement with a reported efficacy of granisetron but not of ondansetron in patients with irritable bowel syndrome.
Eur J Pharmacol 1996 Dec 27
PMID:Response heterogeneity of 5-HT3 receptor antagonists in a rat visceral hypersensitivity model. 900 25

Functional disorders like functional dyspepsia, irritable bowel syndrome and non-cardiac chest pain are common diseases. No organic lesion can be found to explain the often disabling symptoms. Typical features of functional dyspepsia are anxiety, depression, neuroticism, visceral hypersensitivity, abnormal autonomic nerve activity with a weak vagal and an higher sympathetic tone, and impairment of gastric accommodation. This last abnormality may be due to weak vagal tone and poor adaptive relaxation of the proximal stomach. The degree of dysfunction of the variables is sometimes correlated, suggesting that the pathogenetic factors may be interacting in a viscious circle. Medical therapy is often unsuccessful, but extensive research in the field has given better insight into the pathophysiological mechanisms, giving hope for new therapeutic modalities, including visceral analgesics. It may still be difficult, however, to distinguish organic from functional disorders. Reliable tests of visceral hypersensitivity would be helpful in this respect.
Tidsskr Nor Laegeforen 1996 Dec 10
PMID:[When you get a gut feeling...]. 901 85


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