Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Motilin and ghrelin are released from the upper gut during fasting, to stimulate gastric motility. Additional actions of ghrelin (e.g. changes in appetite, nausea or endocrine functions) improve the possibility of using ghrelin receptor agonists to treat complex disorders such as functional dyspepsia. However, changes in endocrine functions increase the risk of unacceptable side effects. By comparison, the more restricted prokinetic activity of motilin limits the therapeutic possibilities but improves the risk:benefit ratio. Compounds targeting both receptors are in development. Recently, additional peptides have been identified from preproghrelin (obestatin) and prepromotilin. These exert biological activity but their pathophysiological significance is unknown.
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PMID:Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases. 1834 99

In tertiary referral patients, there is association between altered sleep patterns, functional bowel disorders and altered gut motor function. Body mass index (BMI) is also associated with gastrointestinal (GI) symptoms including diarrhoea, and with sleep disturbances. Our hypothesis is that sleep disturbances are associated with GI symptoms, and this is not explained by BMI. A 48-item-validated questionnaire was mailed to 6939 community participants in Olmsted County, MN. The survey included GI symptoms, sleep disturbance, daily lifestyle and quality of life (QOL). Independent contributions of sleep disturbance to individual symptoms were assessed using logistic regression adjusting for age, gender, lifestyle and mental health status. The association of an overall sleep score with an overall symptom score was examined and the ability of both scores to predict SF-12 physical and mental functioning scores assessed in multiple linear regression models. Among 3228 respondents, 874 (27%) reported trouble staying asleep. There was a significant correlation of overall sleep scores with overall GI symptom scores (partial r = 0.28, P < 0.001). Waking up once nightly at least four times a month was significantly associated with pain, nausea, dysphagia, diarrhoea, loose stools, urgency and a feeling of anal blockage. Trouble falling asleep was significantly associated with rectal urgency. Associations were independent of gender, age, lifestyle factors and BMI. Overall, sleep scores and GI symptom scores were both significant independent predictors of impaired QOL. In the community, reporting poor sleep is associated with upper and lower GI symptoms, but this is independent of BMI.
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PMID:Sleep disturbances are linked to both upper and lower gastrointestinal symptoms in the general population. 1882 89

5-Hydroxytryptamine (5-HT) is a major transmitter molecule within the gastrointestinal tract. It is contained in enterochromaffin (EC) cells, which form part of the epithelial lining of the gut and in enteric neurones in the submucosal and myenteric plexuses. 5-HT is present in murine mucosal mast cells in the lamina propria and some studies have suggested that human mast cells may also contain 5-HT especially in conditions associated with mastocytosis. The strategic positioning of the enteric and extrinsic sensory innervation in close proximity to these sources of 5-HT, in conjunction with their demonstrated sensitivity to this mediator, suggests the involvement of 5-HT in the transduction of visceral stimuli and reflex responses affecting motor and secretory function. Under physiological conditions, the release of 5-HT from these storage sites may result in the orchestration of reflexes responsible for transit of material along the bowel at a rate that is appropriate for digestion and absorption of nutrients. However, in the pathophysiological state, 5-HT acting together with other inflammatory mediators may cause inappropriate intestinal secretomotor activity and/or initiate sensations such as nausea or discomfort/pain. Current evidence suggests that the bioavailability of 5-HT within the gut wall is altered in a number of post-inflammatory models of gut dysfunction with increased numbers of EC cells and mast cells with increased 5-HT content in proximity to sensory nerve endings, and decreased serotonin reuptake mechanisms. Changes may also occur in the sensory innervation or pathways within the central nervous system. These processes may contribute to pain mechanisms in the irritable bowel syndrome, in which visceral hypersensitivity is a predominant feature and may also contribute to motor dysfunction leading to altered bowel habit.
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PMID:5-HT system in the gut: roles in the regulation of visceral sensitivity and motor functions. 1892 45

CCK mediates the effects of nutrients on gastrointestinal motility and appetite. Intravenously administered CCK stimulates pyloric pressures, increases plasma PYY, and suppresses ghrelin, all of which may be important in the regulation of appetite and energy intake. The dose-related effects of exogenous CCK on gastrointestinal motility and gut hormone release, and the relationships between these effects and those on energy intake, are uncertain. We hypothesized that 1) intravenous CCK-8 would have dose-dependent effects on antropyloroduodenal (APD) pressures, plasma PYY and ghrelin concentrations, appetite, and energy intake and 2) the suppression of energy intake by CCK-8 would be related to the stimulation of pyloric motility. Ten healthy men (age 26 +/- 2 yr) were studied on four separate occasions in double-blind, randomized fashion. APD pressures, plasma PYY and ghrelin, and appetite were measured during 120-min intravenous infusions of 1) saline ("control") or 2) CCK-8 at 0.33 ("CCK0.33"), 3) 0.66 ("CCK0.66"), or 4) 2.0 ("CCK2.0") ng.kg(-1).min(-1). After 90 min, energy intake at a buffet meal was quantified. CCK-8 dose-dependently stimulated phasic and tonic pyloric pressures and plasma PYY concentrations (r > 0.70, P < 0.05) and reduced desire to eat and energy intake (r > -0.60, P < 0.05) without inducing nausea. There were relationships between basal pyloric pressure and isolated pyloric pressure waves (IPPW) with plasma CCK (r > 0.50, P < 0.01) and between energy intake with IPPW (r = -0.70, P < 0.05). Therefore, our study demonstrates that exogenous CCK-8 has dose-related effects on APD motility, plasma PYY, desire to eat, and energy intake and suggests that the suppression of energy intake is related to the stimulation of IPPW.
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PMID:Dose-dependent effects of cholecystokinin-8 on antropyloroduodenal motility, gastrointestinal hormones, appetite, and energy intake in healthy men. 1895 13

It has been proposed that thiamine deficiency after gastric bypass surgery in obese patients results from prolonged nausea and emesis. We hypothesized that thiamine deficiency is induced by altered gut ecology. This report includes 2 retrospective studies of obese patients who underwent Roux-en-Y gastric bypass surgery at our institution from 1999 to 2005. In the first study, 80 patients (52 women and 28 men) had measurement of whole-blood thiamine diphosphate level and serum folate level. In these 80 patients, 39 (49%) had thiamine diphosphate levels less than the lower limit of the reference range, and 28 (72%) of the 39 had folate levels higher than the upper limit of the reference range, an indicator of small intestinal bacterial overgrowth. In 41 patients with normal thiamine levels, only 14 (34%) had folate levels higher than the upper limit of the reference range (chi(2) test, P < .01). In the second study, 21 patients (17 women and 4 men) had thiamine diphosphate levels less than the lower limit of the reference range and abnormal glucose-hydrogen breath tests, consistent with small intestinal bacterial overgrowth. Fifteen patients received oral thiamine supplements, but repeated thiamine levels remained low in all 15. Nine of these patients then received oral antibiotic therapy; repeated thiamine levels were found to be normal in all 9 patients. These results support the hypothesis that small intestinal bacterial overgrowth results from altered gut ecology and induces thiamine deficiency after gastric bypass surgery in obese patients.
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PMID:Small intestinal bacterial overgrowth and thiamine deficiency after Roux-en-Y gastric bypass surgery in obese patients. 1908 22

Chronic constipation and irritable bowel syndrome are heterogeneous disorders characterized by altered bowel habits, abdominal discomfort and/or difficult defecation. These conditions have a significant impact on patients' quality of life, as well as on the US economy, both in terms of healthcare costs and lost productivity. Treatment typically begins with lifestyle changes, increased fiber intake and osmotic and stimulant laxative intake. However, treatments for constipation vary in terms of their efficacy and safety. Furthermore, surveys of physicians and patients have revealed a strong desire for improved therapeutic options. Lubiprostone is a synthetic bicyclic fatty acid that is gut selective and stimulates type 2 chloride channels, resulting in increased chloride, sodium and water secretion into the lumen. The increased fluid secretion causes luminal distension, secondary peristalsis and laxation. Randomized Phase III trials have shown that lubiprostone is efficacious in the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. The US FDA has approved lubiprostone at a dose of 24 microg twice daily for the treatment of chronic idiopathic constipation in adults, and at a dose of 8 microg twice daily for irritable bowel syndrome with constipation in adult women. Nausea, diarrhea and headaches are the most commonly reported side effects. In long-term studies, lubiprostone appears to be safe.
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PMID:Lubiprostone for constipation and irritable bowel syndrome with constipation. 1909 Jul 33

Irritable bowel syndrome (IBS) is a chronic, highly prevalent gastrointestinal motility disorder characterized by abdominal discomfort/pain associated with altered bowel habits such as diarrhea or constipation or both. Current therapy for the constipation-predominant form (IBS-C) comprises fiber or osmotic or stimulant laxatives. However, these may exacerbate the condition or cause electrolyte disturbances. Lubiprostone is a novel selective chloride channel-2 activator that increases fluid secretion in the intestinal apical cell membrane, increasing gut motility and frequency of stool passage, and alleviating abdominal discomfort/pain. Lubiprostone has very low systemic bioavailability and cannot be quantitated in blood, but its active metabolite, M3, has been pharmacokinetically profiled. Lubiprostone reaches peak plasma concentrations within approximately 1 h and has a half-life of 0.9-1.4 h. Despite this short half-life, lubiprostone can be administered orally twice daily. Its efficacy in IBS-C has been demonstrated in two phase III studies; spontaneous bowel movement frequency increased and stool consistency improved, whereas straining, bloating and severity of constipation decreased. The beneficial effects continued for up to 4 weeks after cessation of lubiprostone. Lubiprostone was well tolerated in the long-term, with nausea and diarrhea being the commonest adverse events. Further studies are ongoing in opioid-induced bowel dysfunction.
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PMID:Lubiprostone--a novel treatment for irritable bowel syndrome with constipation. 1913 19

Bezoars are the most common foreign bodies of the gastrointestinal tract. Clinical manifestations vary depending on the location of the bezoar, from no symptoms to acute abdominal syndrome. The ingestion of cling film, which is used for preserving food, may lead to a mechanical obstruction of the gut, especially at the second portion of the duodenal segment, and could manifest with abdominal pain, epigastric distress, nausea, vomiting, and fullness. We report the case of a 72-year-old man who presented with gastric outlet obstruction after accidentally ingesting cling film. He completely recovered after it was endoscopically removed. Cling film is not toxic but has erosive effects. Endoscopic removal of such material is recommended. Moreover, psychiatric intervention and management is imperative to prevent recurrence in such cases.
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PMID:Subacutely formed bezoar resulting from accidentally ingested industrial material. 1937 76

Incretins such as glucagon-like peptide-1 (GLP-1) are gut-derived hormones that stimulate insulin secretion and suppress glucagon secretion, thus playing a key role in glucose homeostasis. While incretin mimetics and enhancers are approved for treatment of outpatients with diabetes, evidence is only starting to accumulate regarding the therapeutic potential of incretins in hospitalized patients. Small exploratory studies suggest that GLP-1 safely reduces hyperglycemia without causing hypoglycemia, a key advantage over insulin if efficacy is established in larger studies. Potential limitations include the need for a continuous infusion for delivery, attenuation but not normalization of glucose levels, increased deceleration of gastric emptying and nausea. The exact mechanism of action, dosing, adverse effects, patient subgroups that would be most suitable and safety of combination treatment with insulin remain to be studied. While promising, additional research is required studying effects on hard clinical endpoints.
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PMID:Incretins in the ICU: is insulin on its way out? 1943 67

Anticancer agents, such as cisplatin, stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice do not possess a vomiting response, and, therefore, in these species, the ingestion of kaolin clay (a pica response) has been used as an index of malaise. In the rat, cisplatin-induced kaolin intake is inhibited by antiemetic treatments. In addition, cisplatin activates vagal afferent fibers in the gut, and kaolin intake induced by cisplatin is largely dependent on an intact vagus. Nevertheless, little is known about the brain pathways controlling pica. We investigated the role of the lateral parabrachial nucleus (lPBN), a major visceral afferent link between the hindbrain and forebrain, in cisplatin-induced c-Fos expression and pica. Injection of cisplatin (6 mg/kg ip) produced c-Fos expression in the ventrolateral (external) lPBN, a region receiving viscerosensory input. In rats with bilateral ibotenic acid lPBN lesions, cisplatin treatment substantially increased kaolin intake compared with controls ( approximately 30 g vs. approximately 5 g, respectively, over 24 h). Food intake was reduced by cisplatin treatment and by apomorphine, an emetic agent that acts centrally. Unlike cisplatin, however, apomorphine stimulated kaolin intake to a similar degree in both the lesioned and control rats, suggesting that lPBN damage neither produces nonspecific effects nor enhances malaise in general. These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats.
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PMID:Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat. 1971 Mar 91


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