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)

H(2)S functions as a neuromodulator and exerts anti-inflammatory activities. Recent data indicate that irritable bowel syndrome (IBS) is linked to inflammation of the gastrointestinal tract. In this study, we have investigated the role of a novel H(2)S-releasing derivative of mesalamine (5-amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester, ATB-429) in modulating nociception to colorectal distension (CRD), a model that mimics some features of IBS, in healthy and postcolitic rats. Four graded (0.4-1.6 ml of water) CRDs were produced in conscious rats, and colorectal sensitivity and pain were assessed by measuring the abdominal withdrawal response and spinal c-Fos expression. In healthy rats, ATB-429 dose dependently (25, 50, or 100 mg/kg) attenuated CRD-induced hypersensitivity and significantly inhibited CRD-induced overexpression of spinal c-FOS mRNA, whereas mesalamine had no effect. ATB-429-induced antinociception was reversed by glibenclamide, a ATP-sensitive K(+) (K(ATP)) channel inhibitor. The antinociceptive effect of ATB-429 was maintained in a rodent model of postinflammatory hypersensitivity (4 weeks after colitis induction). At a dose of 100 mg/kg, ATB-429 reversed the allodynic response caused by CRD in postcolitic rats. Colonic cyclooxygenase-2 and interkeukin-1beta mRNA and spinal c-FOS mRNA expression were significantly down-regulated by ATB-429, but not by mesalamine. ATB-429, but not mesalamine, increased blood concentrations of H(2)S in both healthy and postcolitic rats. Taken together, these data suggest that ATB-429 inhibits hypersensitivity induced by CRD in both healthy and postcolitic, allodynic rats by a K(ATP) channel-mediated mechanism. This study provides evidence that H(2)S-releasing drugs might have beneficial effects in the treatment of painful intestinal disorders.
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PMID:5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity. 1685 78

Despite its beneficial effect in IBS patients, the mechanism of action of the 5-HT3 receptor (5-HT3R) antagonist alosetron is still incompletely understood. We aimed to characterize the effect and site(s) of action in a model of stress-induced sensitization of visceral nociception in rats. Adult male Wistar rats were equipped for recording of visceromotor response (VMR) to phasic colorectal distension (CRD; 10-60 mmHg). VMR to CRD was recorded 24 h after an acute session of water avoidance (WA) stress (post-WA). Baseline and post-WA responses were measured in rats exposed to WA or sham-WA, treated with alosetron at 0.3 mg/kg subcutaneously (s.c.) 25 nmol intrathecally (i.t.) or vehicle before post-WA CRD. Some rats were treated with capsaicin/vehicle on the cervical vagus nerve and received alosetron (0.3 mg/kg, s.c.) 15 min before post-WA CRD. WA stress led to visceral hyperalgesia 24 h later. Alosetron (0.3 mg/kg, s.c.), failed to inhibit WA-induced exacerbation of VMR to CRD. Stress-induced visceral hyperalgesia was abolished when alosetron was injected intrathecally (P<0.05) in intact rats or subcutaneously (0.3 mg/kg) in capsaicin-pretreated animals (P<0.05). Capsaicin-pretreatment did not affect the exacerbating effect of stress on visceral sensitivity. Alosetron had no inhibitory effect on normal visceral pain responses when administered subcutaneously or intrathecally. We demonstrated that 5-HT3Rs on central terminals of spinal afferents are engaged in the facilitatory effect of stress on visceral sensory information processing. In addition, we showed that stress-induced sensitization of visceral nociception is independent of 5-HT3R activation on vagal afferents.
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PMID:Dual role of 5-HT3 receptors in a rat model of delayed stress-induced visceral hyperalgesia. 1716 36

Irritable bowel syndrome (IBS) in the outpatient with chronic inflammatory bowel disease (IBD) is a difficult but important challenge to recognize and treat. It is very helpful to have effective treatment approaches for IBS that are practical and use minimal medications. Because of the underlying chronic inflammation in IBD, IBS symptoms occur with increased frequency and severity, secondary to increased hypersensitivity to foods and beverages that stimulate the gastrointestinal tract. This paper discusses how to treat IBS in the IBD outpatient, with emphasis on using a food and beverage intolerance, avoidance diet. The adverse effects of many foods and beverages are amount dependent and can be delayed, additive, and cumulative. The specific types of foods and beverages that can induce IBS symptoms include milk and milk containing products; caffeine containing products; alcoholic beverages; fruits; fruit juices; spices; seasonings; diet beverages; diet foods; diet candies; diet gum; fast foods; condiments; fried foods; fatty foods; multigrain breads; sourdough breads; bagels; salads; salad dressings; vegetables; beans; red meats; gravies; spaghetti sauce; stews; nuts; popcorn; high fiber; and cookies, crackers, pretzels, cakes, and pies. The types of foods and beverages that are better tolerated include water; rice; plain pasta or noodles; baked or broiled potatoes; white breads; plain fish, chicken, turkey, or ham; eggs; dry cereals; soy or rice based products; peas; applesauce; cantaloupe; watermelon; fruit cocktail; margarine; jams; jellies; and peanut butter. Handouts that were developed based upon what worsens or helps IBS symptoms in patients are included to help patients learn which foods and beverages to avoid and which are better tolerated.
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PMID:Treatment of irritable bowel syndrome in outpatients with inflammatory bowel disease using a food and beverage intolerance, food and beverage avoidance diet. 1720 44

Ramosetron is a potent and selective serotonin (5-HT)(3) receptor antagonist that has been shown to affect abnormal colonic function and abdominal pain in animals. Ramosetron (0.3 to 100 microg/kg, p.o.) has been found to significantly suppress abnormal defecation induced by conditioned-fear stress (CFS), restraint stress, corticotropin releasing factor (CRF) and 5-HT in rats and mice, and these effects were more potent than those of alosetron, cilansetron or loperamide. On the other hand, ramosetron (3,000 microg/kg, p. o., once daily for 7 days) did not inhibit normal defecation in dogs while tiquizium significantly inhibited it. Ramosetron (3 to 100 microg/kg, p. o.) also significantly prevented CFS-induced acceleration of colonic transit and CRF-induced abnormal water transport in rats, respectively. Moreover, ramosetron (0.3 to 3 microg/kg, p. o.) significantly suppressed restraint stress-induced decrease in colonic pain threshold, an effect not observed with loperamide. These results indicate that ramosetron produce beneficial clinical effects on IBS symptoms.
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PMID:Pharmacological profile of ramosetron, a novel therapeutic agent for IBS. 1732 87

All cases of diarrhea involve increased fecal excretion of water. Understanding the mechanisms of infectious diarrhea requires review of the physiology of water and electrolyte absorption. Every day, 8 to 9 liters of fluid flow into the intestine, most of it reabsorbed in the small bowel. There are 2 main types of infectious diarrhea: secretory noninvasive diarrhea, such as cholera, due to impairment of water absorption mechanisms in the small bowel and inducing watery stools and dehydration; and enteroinvasive diarrhea, due to alteration of the colonic mucosa, inducing dysentery. Most cases of infectious diarrhea are acute. Some pathogens, mainly parasites, can induce chronic diarrhea. A HIV serology is then warranted. Some patients develop chronic irritable bowel syndrome after acute gastroenteritis.
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PMID:[Pathophysiology of tropical diarrhea]. 1732 66

Constipation has an estimated prevalence of 15% in the general population. However, the etiopathogenesis of this condition remains relatively obscure. This study sought to identify potentially novel risk factors for chronic constipation. A valid self-report questionnaire was mailed to an age- and gender-stratified random sample of Olmsted County, Minnesota residents aged 30-64 years. A logistic regression model that adjusted for age, gender and somatic symptom score (SSC) was used to identify factors associated with chronic constipation. People reporting symptoms of irritable bowel syndrome (IBS) were excluded. Of the 892 eligible subjects, 653 (73%) returned the survey. Among the 523 subjects not reporting IBS symptoms, chronic constipation was reported by 93 (18%) of the respondents. Chronic constipation was significantly associated with use of acetaminophen [>or=7 tablets per week, OR = 2.7 (1.1-6.6)]; aspirin [OR = 1.7 (1.0-2.7)]; non-steroidal anti-inflammatory drugs [OR = 1.8 (1.1-3.0)]; and SSC. No association was detected for age, gender, body mass index, marital status, smoking, alcohol, coffee, education level, food allergy, exposure to pets, stress, emotional support, or water supply. Chronic constipation is associated with use of acetaminophen, aspirin and non-steroidal anti-inflammatory drugs. The explanation of these associations requires further investigation.
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PMID:Risk factors for chronic constipation and a possible role of analgesics. 1798 75

The purpose of this study was to prepare tegaserod maleate (TM) pH-dependent tablets and evaluate their advantages as a sustained release delivery system. TM, insoluble in water and unstable in gastric milieu, was formulated into pH-dependent tablets coated with combinations of two methacrylic acid copolymers - Eudragit L100 and Eudragit S100. The influence of core tablet compositions, polymer combination ratios and coating levels on the in vitro release rate of TM from coated tablets was investigated. The optimum formulation was evaluated for in vitro release rate and in vivo bioavailability study on beagle dogs. In addition, physico-chemical properties of the drug, including solubility at different pH and temperatures, and dissociation constant were determined. The results showed that no drug was released in 0.1 mol/L hydrochloric acid within 2h, and about 90% of the drug was released in the pH 6.8 phosphate buffer within 12h in a sustained manner. The pharmacokinetic investigation showed that TM pH-dependent tablets exhibited a sustained plasma concentration, a lag time of approximately 2.3h and a relative bioavailability of 159% compared to plain tablets. A close correlation existed between the in vitro release rate of the pH-dependent system and its in vivo absorption percentage. The results of the present study have demonstrated that the pH-dependent tablet system is a promising vehicle for preventing rapid hydrolysis in gastric milieu and improving oral bioavailability of TM for the treatment of irritable bowel syndrome.
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PMID:In vitro and in vivo evaluation of tegaserod maleate pH-dependent tablets. 1803 78

Although incomplete fructose absorption has been implicated to cause gastrointestinal symptoms, foods containing high fructose corn syrup (HFCS) contain glucose. Glucose increases fructose absorption in healthy subjects. Our hypothesis was that fructose intolerance is less prevalent after HFCS consumption compared to fructose alone in healthy subjects and irritable bowel syndrome (IBS). Breath hydrogen levels and gastrointestinal symptoms were assessed after 40 g of fructose (12% solution) prepared either in water or as HFCS, administered in double-blind randomized order on 2 days in 20 healthy subjects and 30 patients with IBS. Gastrointestinal symptoms were recorded on 100-mm Visual Analogue Scales. Breath hydrogen excretion was more frequently abnormal (P < 0.01) after fructose (68%) than HFCS (26%) in controls and patients. Fructose intolerance (i.e. abnormal breath test and symptoms) was more prevalent after fructose than HFCS in healthy subjects (25% vs. 0%, P = 0.002) and patients (40% vs. 7%, P = 0.062). Scores for several symptoms (e.g. bloating r = 0.35) were correlated (P < or = 0.01) to peak breath hydrogen excretion after fructose but not HFCS; in the fructose group, this association did not differ between healthy subjects and patients. Symptoms were not significantly different after fructose compared to HFCS. Fructose intolerance is more prevalent with fructose alone than with HFCS in health and in IBS. The prevalence of fructose intolerance is not significantly different between health and IBS. Current methods for identifying fructose intolerance should be modified to more closely reproduce fructose ingestion in daily life.
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PMID:Comparison of breath testing with fructose and high fructose corn syrups in health and IBS. 1822 Dec 51

Differences in brain responses to aversive visceral stimuli may underlie previously reported sex differences in symptoms as well as perceptual and emotional responses to such stimuli in patients with irritable bowel syndrome (IBS). The goal of the current study was to identify brain networks activated by expected and delivered aversive visceral stimuli in male and female patients with chronic abdominal pain, and to test for sex differences in the effective connectivity of the circuitry comprising these networks. Network analysis was applied to assess the brain response of 46 IBS patients (22 men and 24 women) recorded using [15O] water positron emission tomography during rest/baseline and expected and delivered aversive rectal distension. Functional connectivity results from partial least squares analyses provided support for the hypothesized involvement of 3 networks corresponding to: 1) visceral afferent information processing (thalamus, insula and dorsal anterior cingulate cortex, orbital frontal cortex), 2) emotional-arousal (amygdala, rostral and subgenual cingulate regions, and locus coeruleus complex) and 3) cortical modulation (frontal and parietal cortices). Effective connectivity results obtained via structural equation modeling indicated that sex-related differences in brain response are largely due to alterations in the effective connectivity of emotional-arousal circuitry rather than visceral afferent processing circuits. Sex differences in the cortico-limbic circuitry involved in emotional-arousal, pain facilitation and autonomic responses may underlie the observed differences in symptoms, and in perceptual and emotional responses to aversive visceral stimuli.
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PMID:Sex differences in brain activity during aversive visceral stimulation and its expectation in patients with chronic abdominal pain: a network analysis. 1845 Apr 81

Local or village chickens are the major source of poultry products in less developed countries, but information is limited on their susceptibility or resistance to diseases. In this work, 6-week-old local Nigerian chickens, pullets and broilers were used. One day before infection the mean body weight of the broilers was more than twice that of the pullets and local chickens. The bursa: body weight (B:BW) indices of the pullets and local chickens were similar, but were significantly higher than those of broilers. Following inoculation intraocularly with pathogenic infectious bursal disease virus (IBDV) drowsiness, drop in feed and water consumption, and diarrhoea were observed among the local chickens and pullets on day 2 post inoculation (p.i.) and in the broilers on day 3 p.i. Body weight losses from 1 to 11 days p.i. were significantly higher in the local chickens and pullets than in the broilers, total mortalities being 17.6, 50.0 and 61.51% in broilers, pullets and local chickens, respectively. Necropsy showed that dehydration and proventricular haemorrhages occurred most frequent in the local chickens. The response correlated with the B:BW indices on day 14 p.i. This showed that local Nigerian chickens are more susceptible to IBD than broilers and slightly more susceptible than pullets, explaining earlier reports that mortality due to IBD was higher in pullets or light breeds of chicken than in broilers or heavy breeds.
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PMID:Comparative study of the resistance or susceptibility of local Nigerian and exotic chickens to infectious bursal disease. 1848 82


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