Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disorders of gastric emptying are observed in many clinical situations. Their symptoms are diverse and correlate poorly with the objective abnormalities of gastric emptying. The underlying mechanism consists of abnormalities of basal electrical rhythm, fundic compliance, post-prandial antral motricity and, above all, antro-pyloro-duodenal co-ordination, associated to varying degrees. Among possible causes 3 clinical situations predominate: diabetes mellitus, functional gastrointestinal disorders (idiopathic dyspepsia) and sequelae of gastric surgery where retention of solids and accelerated evacuation of liquids may coexist in the same patient. Treatment of gastric incontinence rests, almost exclusively, on dietary measures, but several drugs, such as metoclopramide, domperidone and cisapride, are available to treat gastric stasis. Other compounds, notably motilin agonists (erythromycin and its derivatives) are currently being evaluated and will reinforce this therapeutic armentarium in a not too distant future.
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PMID:[Disorders of gastric emptying]. 138 39

The Plasma motilin level in 44 cases patients with Spleen-Yin deficiency (SYD) was observed and compared with Spleen-Qi Insufficiency (SQI), the normal control group. SYD patients were treated using self-made Shen Rou Yang Zhen Tang oral liquor. The results showed that plasma motilin level was higher significantly than that of the control group (P < 0.01), but was remarkably lower than that of SQI. The difference was significant among the three groups (P < 0.01). The abnormal incidence of positive plasma motilin was 65.91% and 75.00% respectively. It is conjectured that the plasma motilin level in SYD was related to excitability of vagus nerve, disturbance of gastro-intestinal internal environment, indigestion and malabsorption of GI tract.
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PMID:[Study on motilin and spleen-yin deficiency]. 770 31

Thirty-two patients of non-ulcer dyspepsia (NUD) with gallbladder hypokinesia treated by oral erythromycin administration 0.125g three times daily for two weeks. Before and after oral erythromycin administration, gallbladder volumes were determined by ultrasound, and plasma motilin concentration were determined by radioimmunoassay. The results showed that before and after oral erythromycin administration, maximal percentage emptying of gallbladder were 48.24 +/- 8.30ml vs 69.74 +/- 10.78ml (P < 0.01), plasma motilin were 361.28 +/- 87.92ng/L vs 394.97 +/- 134.27ng/L (P > 0.05). It is indicated that erythromycin could reduce fasting and postprandial residual gallbladder volumes and increases maximal percentage emptying of gallbladder. It suggests that erythromycin might have an agonist action on the motilin receptor as an agonist action on the motilin receptor as an exogenously administrated motilin.
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PMID:[Clinical study of erythromycin action on gallbladder motility in patients with non-ulcer dyspepsia]. 786 25

In clinical practice, exogenous pancreatic enzymes are administered for the treatment of pancreatogenic steatorrhea or with the intention to relieve pain due to chronic pancreatitis. Moreover, a large number of patients take pancreatin (i.e., exogenous pancreatic enzymes) for functional dyspepsia. The effect of exogenous pancreatic enzymes on the enteropancreatic axis is a complex issue. Intraduodenal but not intrajejunal protease activity appears to exert a dose-dependent negative feedback on exocrine pancreatic secretion. Only enzymes with a proteolytic activity but not amylase and lipase exert a control on pancreatic secretion. The mechanism responsible for this feedback regulation is debated, but the cholinergic system seems to play a major role. Intraduodenal pancreatic enzymes (pancreatin) lead to an increased release of pancreatic polypeptide but do not affect the release of insulin and glucagon. In addition, pancreatic enzymes have an influence on the release of some gastrointestinal hormones (i.e., cholecystokinin, motilin, gastric inhibitory polypeptide). Neither exogenous nor endogenous pancreatic enzymes seem to play a major role in the regulation of interdigestive gastrointestinal motility. However, an adequate rate of postprandial pancreatic output is required to control gastric emptying. Current knowledge on the effect of exogenous pancreatic enzymes on the enteropancreatic axis, gut peptide release and gastrointestinal motility are updated in the present article.
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PMID:Effect of exogenous pancreatic enzymes on gastrointestinal and pancreatic hormone release and gastrointestinal motility. 822 68

Liver affects the release and clearance of many hormones, but the interactions between gastrointestinal peptides and liver function are obscure. Aim of this study was to evaluate plasma concentrations of gastrointestinal peptides during acute hepatic cytonecrosis and during liver regeneration in man. The study was performed in ten patients with viral hepatitis (8 virus A, 2 virus B) in the acute phase (alanine transaminase = 3073 +/- 739 U/L; mean +/- SEM), and at days 7, 45 and 52 after the initial evaluation, during clinical and biochemical recovery (52nd day, alanine transaminase = 77 +/- 26). Plasma concentrations of the following hormones were evaluated by radioimmunoassay: glucagon, insulin, gastrin, vasoactive intestinal peptide, bombesin, neurotensin, cholecystokinin, secretin and motilin. Only serum bombesin and cholecystokinin were significantly (p < 0.01) increased in the acute phase of hepatitis (bombesin: 138 +/- 21 pg/ml; cholecystokinin: 57 +/- 7 pg/ml); they returned to normal values during convalescence (bombesin: 60 +/- 8; cholecystokinin: 31 +/- 4). During hepatocellular necrosis, plasma concentrations of cholecystokinin and bombesin, which are both cellular growth factors and regulatory signals of food introduction and satiety state, were increased by 83% and 130%, respectively. Increase of these hormones may cause the dyspepsia and lack of appetite that characterizes the initial phase of acute viral hepatitis.
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PMID:Gastrointestinal peptide hormones in acute viral hepatitis. 878

Previous studies have shown that patients with chronic alcohol ingestion may show a variety of morphological and functional alterations in the small intestine. In this study, we have focused on the neuroendocrine system in the duodenal mucosa in chronic alcoholics; an area little studied. Twenty-three defined chronic alcoholics admitted to the hospital for detoxification underwent clinical examination, followed by upper gastrointestinal endoscopy and blood tests on average 4 days after the most recent alcohol intake. Biopsy specimens were taken from the distal part of the descending duodenum for both immunohistochemical and routine histological examination. The control group consisted of 25 patients referred for upper endoscopy mainly because of dyspepsia (ulcer, reflux type), but who were otherwise healthy. A normal carbohydrate-deficient transferrin and a history of low alcohol consumption (<40 g/week) were required for inclusion in the control group. The tissue specimens were studied using antisera for the following neuropeptides: cholecystokinin, galanin, gastric inhibitory peptide (GIP), glucagon, motilin, neuropeptide Y, pituitary adenylyl cyclase activating peptide, secretin, serotonin, somatostatin, substance P, vasoactive intestinal polypeptide and protein gene product, as a general marker for neurones and cells of the diffuse neuroendocrine system. The density of nerve fibres was evaluated semi-quantitatively and the number of endocrine cells per unit length of mucosa was counted in sections cut perpendicularly to the mucosal surface. All the different peptidergic nerve fibres in the alcohol group showed higher densities than the corresponding controls. However, this was not a statistically significant difference. A slightly significant increase (P = 0.02) in the numbers of glucagon and GIP cells was seen in the alcohol group. Gastrointestinal symptoms were frequently present (87%) in chronic alcoholics. We suggest that chronic alcohol consumption in man may have a general effect on the peptidergic nerve system and some endocrine cell types in the duodenal mucosa.
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PMID:Neuropeptides in the duodenal mucosa of chronic alcoholic heavy drinkers. 1137 57

This study investigates motilin effects on the proximal stomach in patients with functional dyspepsia (FD) and healthy volunteers. Eight healthy volunteers and 12 patients with FD were infused with synthetic motilin or placebo. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored by visual analog scales. Plasma motilin concentrations were measured by radioimmunoassay. Motilin concentrations and baseline gastric volumes were similar for patients and healthy volunteers. Motilin, compared with placebo, reduced gastric volume by 112 ml [F(29,195); confidence interval (CI) 95%] in patients and by 96 ml [F(-7,200); CI 95%] in healthy volunteers. In patients, motilin decreased compliance by 76 ml/mmHg [F(9,143); CI 95%] compared with placebo, which was similar in volunteers [66 ml/mmHg; F(11,120); CI 95%]. Patients were more nauseous during motilin compared with placebo (P = 0.04), whereas healthy volunteers did not experience nausea. We conclude that in a fasted condition, FD patients have a similar proximal gastric motor response to motilin as healthy volunteers, but experience an exaggerated sensation of nausea.
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PMID:Motilin effects on the proximal stomach in patients with functional dyspepsia and healthy volunteers. 1251 43

Recent research has provided new information about drugs that could be used to treat functional motility disorders. Promotility drugs accelerate gastric emptying or colonic transit and these properties may contribute to their efficacy in treating symptoms associated with gastroparesis, functional dyspepsia or constipation. 5-Hydroxytryptamine4 receptors are targets for drugs (tegaserod, renzapride) that treat symptoms in constipated irritable bowel syndrome patients and in gastroparesis. Drugs acting at motilin (erythromycin) and cholecystokinin-1 (dexloxiglumide) receptors accelerate gastric emptying. Dexloxiglumide might be useful in the treatment of functional dyspepsia particularly that associated with lipid intake. Alvimopan is a mu-opioid receptor antagonist that does not cross the blood brain barrier. Alvimopan is effective in treating postsurgical ileus and perhaps opiate-induced bowel dysfunction. Successes and failures of recent efforts to develop promotility agents revealed opportunities and challenges for developing new promotility drugs. The pharmacological properties of partial agonists might be exploited to develop effective promotility drugs. However, opposing actions of promotility agents on motility (increased contraction vs decreased accommodation) limit the clinical efficacy of drugs with these opposing actions. Selection of appropriate patient populations for evaluation of new drugs is also critical.
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PMID:Basic and clinical pharmacology of new motility promoting agents. 1618 2

Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.
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PMID:Effects of itopride hydrochloride on plasma gut-regulatory peptide and stress-related hormone levels in healthy human subjects. 1671 77

The effects of mitemcinal (GM-611) on the gastrointestinal contractile activity were investigated using chronically implanted force transducers in conscious dogs and were compared with the effects of porcine motilin (pMTL), EM-523 and EM-574. In the interdigestive state, intravenous and oral administration of mitemcinal, EM-523 and EM-574 induced the gastrointestinal contractile activity in a manner similar to pMTL. The contractile activity caused by mitemcinal was suppressed by continuous intravenous infusion of a motilin receptor antagonist. In the digestive state, intravenous and oral administration of mitemcinal, EM-523 and EM-574 also stimulated the gastrointestinal contractile activity. Mitemcinal, EM-523 and EM-574 given intravenously increased the gastric contractile activity in a similar dose range; however, mitemcinal was approximately 10 times more potent than EM-523 and EM-574 when administered orally in the digestive state. These results indicate that the mitemcinal-induced gastrointestinal contractile activity operates via motilin receptors and possesses a higher activity than EM-523 and EM-574 when administered orally in conscious dogs in the digestive state. Mitemcinal may therefore be useful in the treatment of several gastrointestinal disorders involving dysmotility, such as gastroparesis and functional dyspepsia, even when administered orally.
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PMID:Effects of mitemcinal (GM-611), an acid-resistant nonpeptide motilin receptor agonist, on the gastrointestinal contractile activity in conscious dogs. 1742 10


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