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)

Tachykinins belong to an evolutionarily conserved family of peptide neurotransmitters. The mammalian tachykinins include substance P, neurokinin A and neurokinin B, which exert their effects by binding to specific receptors. These tachykinin receptors are divided into three types, designated NK1, NK2 and NK3, respectively. Tachykinin receptors have been cloned and contain seven segments spanning the cell membrane, indicating their inclusion in the G-protein-linked receptor family. The continued development of selective agonists and antagonists for each receptor has helped elucidate roles for these mediators, ranging from effects in the central nervous system to the perpetuation of the inflammatory response in the periphery. Various selective ligands have shown both inter- and intraspecies differences in binding potencies, indicating distinct binding sites in the tachykinin receptor. The interaction of tachykinin with its receptor activates Gq, which in turn activates phospholipase C to break down phosphatidyl inositol bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 acts on specific receptors in the sarcoplasmic reticulum to release intracellular stores of Ca2+, while DAG acts via protein kinase C to open L-type calcium channels in the plasma membrane. The rise in intracellular [Ca2+] induces the tissue response. With an array of actions as diverse as that seen with tachykinins, there is scope for numerous therapeutic possibilities. With the development of potent, selective non-peptide antagonists, there could be potential benefits in the treatment of a variety of clinical conditions, including chronic pain, Parkinson's disease, Alzheimer's disease, depression, rheumatoid arthritis, irritable bowel syndrome and asthma.
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PMID:Tachykinins: receptor to effector. 892 4

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.
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PMID:Calcium channel blockers for anxiety disorders? 898 18

Otilonium bromide is a calcium antagonist with a direct myolytic effect, that is indicated in spastic conditions and functional dyskinesias of the gastroenteric apparatus (irritable bowel syndrome) and as a premedication for gastrointestinal endoscopic procedures. The present study assessed otilonium bromide 40 mg PO the night before and 40 mg PO the morning in 49 upper and 14 lower flexible endoscopies in 63 patients, to determine the presence or absence of peristalsis and relaxation of the pylorus. No side effects were observed due to the medication. In 46 (93.8%) upper endoscopies marked relaxation of the gastrointestinal tract and also pylorus relaxation were observed. In 13 (92.8%) lower endoscopies, marked relaxation of the colonic tract was also seen. All patients tolerated well the endoscopies. Otilonium bromide was useful as premedication in order to enable upper and lower endoscopic explorations, because of its spasmolytic effect.
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PMID:[Use of spasmolytic agent otilonium bromide (spasmomen) in digestive endoscopy: a prospective study in 63 patients]. 941 40

A high-fat and low-fiber diet is regarded as a major risk factor for colon cancer by increasing luminal contents of secondary bile acids. Calcium, on the other hand, has been implicated as a possible preventive agent in colon tumor development. In in vitro studies with human colonic epithelium, incubation with the secondary bile acid deoxycholic acid (DCA) induced hyperproliferation of colonic crypt cells which is regarded as a sign of preneoplastic transformation. In the present study the effects of calcium chloride (CaCl2) on DCA-induced hyperproliferation were tested at different stages of DCA-induced cell injury. Colonic biopsies from 36 patients (no tumors, polyps or IBD) were incubated with CaCl2 (1 and 10 mM) and 5 microM DCA which was added to the incubation medium either together with (experiment A), after (experiment B), or before CaCl2 (experiment C). Coincubation of the biopsies with DCA and 10 mM CaCl2 at the same time (experiment A) resulted in a significant reduction of whole crypt labeling index by 12% (p < 0.05), whereas in the other incubation experiments no significant growth-inhibitory effects could be demonstrated for CaCl2. These findings may best be explained by the formation of calcium-bound bile acid salts which lost most of their toxicity for the colonic cells.
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PMID:Effects of calcium and deoxycholic acid on human colonic cell proliferation in vitro. 942 94

Lactose intolerance is widespread, with adult-type hypolactasia being the predominant cause of lactose malabsorption. Daily ingestion of less than 240 mL of milk is well tolerated by most lactose-intolerant adults. Some persons with normal lactase activity may become symptomatic on consumption of products containing lactose. Lactose maldigestion may coexist in adults with irritable bowel syndrome and in children with recurrent abdominal pain. Management consists primarily of dietary changes. People who avoid dairy products should receive calcium supplementation and should be advised to read ingredient labels carefully. Several lactase replacement products are available, but their efficacy varies.
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PMID:When to suspect lactose intolerance. Symptomatic, ethnic, and laboratory clues. 974 7

A composite constituted of calcium phosphate (CaP) granules and a hydrophilic polymer as a carrier (hydroxy-propyl-methyl cellulose, HPMC) was developed to be an injectable bone substitute (IBS, CNRS patent). IBS is a composite and not an ionic cement. The composite obtained is ready to use and sterile. Chemical interactions between organic and inorganic components appeared during the association of the two. The interactions of the CaP and the polymer have been studied using scanning electron microscopy (SEM), electron microprobe (EDX), and high-resolution transmission electron microscopy (HrTEM) SEM revealed a degradation of the granules into smaller particles while EDX was unable to show significant changes in the Ca/P ratio during aging of the composite. With Hr TEM, however, we observed hydrolysis (process of dissolution and precipitation) from the surface to about 13 nm into the HA crystals and occasional dissolution with precipitation of beta-TCP crystals. In HA, the first zone of interaction consisted of a single layer of small globular crystals of 2 to 3 nm in diameter. Numerous lattice patterns in all three axes could be observed. Under the globular crystals zone, the inter-reticular distances of the single crystals appeared enlarged by 1.2% (from 0.817 to 0.827 nm). The enlargement seems to correspond to diffusion of HPO(4) into the crystal lattice. In beta-TCP crystals, dissolution was observed to be several nanometers deep, but globular surface precipitation rarely was observed. With time or after steam sterilization, no changes were observed. These data demonstrate the strong interactions of the hydrophylic polymer with calcium phosphate, but only in the first several nanometers of thickness.
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PMID:Crystal polymer interaction with new injectable bone substitute; SEM and Hr TEM study. 1064 56

Experimental studies have shown that otilonium bromide (OB) inhibits both baseline and chemically or physically stimulated gastrointestinal motility. The spasmolytic activity of OB in the gastrointestinal tract occurs at doses that do not affect gastric secretion or produce typical atropine-like side-effects. The mechanism of action is composite: interference with calcium ion movement from intra- and extracellular sites; blockade of calcium channels; and binding to muscarinic receptors and tachykinin neurokinin-2 receptors. Pharmacokinetic studies have shown that OB accumulates in the lower intestine and has poor systemic absorption. Clinical studies have confirmed OB as a potent spasmolytic drug with a good tolerability profile. Studies in patients with irritable bowel syndrome demonstrated OB to be superior to placebo and reference drugs in parameters such as pain, abdominal distension and motility. The composite and local mechanism of OB action reduces hypermotility and modulates visceral sensation: factors thought to be responsible for pain improvement recorded in clinical trials. The compound is marketed worldwide and no serious adverse events have been reported as yet, confirming its excellent tolerability.
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PMID:Otilonium bromide: a selective spasmolytic for the gastrointestinal tract. 1068 27

The effects of calcium polycarbophil (CP), a water-absorbing polymer, on bowel movement were examined in comparison with known laxatives and anti-diarrheal agents in dogs, a species that resembles humans for stool output. CP increased stool frequency, fecal water content and fecal weight in a dose-dependent manner, but did not induce diarrhea. Sennoside and carboxymethylcellulose sodium (CMC-Na) increased fecal water content and induced diarrhea at lower doses than that which enhanced stool frequency. Trimebutine decreased stool frequency, fecal weight and fecal water content, resulting in inhibition rather than stimulation of defecation. In sennoside-induced diarrhea, loperamide and CP improved stool consistency and this was accompanied by reduced fecal moisture and frequency of diarrhea. In contrast, CMC-Na aggravated stool consistency with increased fecal water content and frequency of diarrhea, and trimebutine had little noticeable effect apart from reducing fecal weight. Our results show that CP has both laxative and anti-diarrheal effects in dogs and differed from conventional laxatives and anti-diarrheal agents. CP may be a suitable agent for treatment of idiopathic constipation, secretory diarrhea and irritable bowel syndrome with alternating constipation and diarrhea and with either predominating in terms of less side effects such as diarrhea or constipation.
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PMID:Calcium polycarbophil, a water absorbing polymer, increases bowel movement and prevents sennoside-induced diarrhea in dogs. 1095 69

Significant recent advances in basic and clinical science have improved our understanding of irritable bowel syndrome (IBS). Sensory abnormalities, particularly visceral hypersensitivity after sensitizing stimulation, indicate neural dysfunction in patients with IBS. This dysfunction could be mediated by N-methyl-D-aspartate or calcium gene-related peptide receptors in the spinal cord. The stress response in the gut is augmented in IBS, which may be related to hypothalamic release of corticotropin-releasing factor. Postinfectious IBS may be related to psychologic factors that allow persistent inflammation. Finally, functional brain imaging has shown augmented central nervous system responses to visceral pain in IBS, particularly in the prefrontal cortex. Low-dose tricyclic antidepressants are useful to control symptoms, and the new serotonin type 3 (5-HT3) receptor antagonists show promise for symptom control.
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PMID:New concepts of irritable bowel syndrome. 1098 Sep 83

Biliary pain resulting from motility disorders is common and may be overlooked due to the difficulty of diagnosing the presence of these disorders. A sound, logical approach to the evaluation and treatment of these specific groups of disorders is essential. In patients who have a gallbladder, we initially exclude the presence of gallstones by use of transcutaneous ultrasonography. If a patient's symptoms are atypical, we initiate therapy (eg, antispasmodics) for irritable bowel syndrome. Subsequently, we perform a quantitative cholescintigraphy with a low-dose infusion of cholecystokinin in patients with typical symptoms and in those with persistent atypical symptoms. Those patients who have abnormally low gallbladder ejection fractions are subsequently referred for laparoscopic cholecystectomy. In postcholecystectomy patients, a standard approach should include obtaining serum liver associated laboratory chemistries, amylase and lipase levels, and a transcutaneous ultrasound to measure bile duct size. Endoscopic retrograde cholangiopancreatography (ERCP) is done to measure bile duct size, assess biliary duct emptying, and exclude other etiologies for pain. In patients with more than two abnormal findings on these tests (type I sphincter of Oddi dyskinesia), we recommend performing an empiric endoscopic biliary sphincterotomy. In patients with no objective abnormalities (type III sphincter of Oddi dyskinesia), it is appropriate to begin medical therapy with antispasmodics and calcium-channel antagonists. In individuals who have one or two abnormalities (type II sphincter of Oddi dyskinesia) we prefer endoscopic biliary sphincterotomy; however, these individuals are offered the opportunity to have endoscopic biliary manometry performed in order to establish a clear diagnosis. If patients refuse this procedure, after careful explanation of risks, alternatives, and possible benefits of the procedure, empiric endoscopic biliary sphincterotomy is performed.
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PMID:Biliary Tract Dysmotility. 1109 61


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