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

The use of reflectance spectrophotometry (RS) for mucosal hemodynamic measurement relies on the recognition of changes in indexes of mucosal hemoglobin concentration and oxygen saturation. Endoscopic application in clinical studies has confirmed important observations demonstrated in animal experiments. The vasoconstriction induced by propranolol, vasopressin, glypressin, or somatostatin in the portal hypertensive gastric mucosa and the reduction of gastroduodenal mucosal perfusion by nonsteroidal anti-inflammatory drugs (NSAIDs) or smoking, mesenteric venoconstriction associated with systemic hypoxia, and acid-induced duodenal hyperemia are important examples. Prognostic predictions include the development of stress-induced gastric ulcerations in patients with significant reductions in gastric perfusion after thermal or head injury, or the demonstration of delayed gastric or duodenal ulcer healing when the hyperemia at the ulcer margin fails to materialize. In mechanical-ventilator-dependent patients with sepsis, a significantly reduced gastric mucosal RS measurement portends a grave prognosis (mortality >80%). Recent advances in technology resulted in the construction and validation of instruments for visible light spectroscopy. Measurements focused on tissue oxygen saturation demonstrated epinephrine and vessel-ligation-induced vasoconstriction, the absence of ischemia in radiation-induced rectal telangiectasias, and gut ischemia responsive to revascularization treatment. Endoscopic RS and visible light spectroscopy are suitable for assessing the role of blood flow in conditions with a lesser degree of ischemia and for testing the hypothesis that functional dyspepsia and dysmotility syndromes may be due to gut ischemia.
 ...
PMID:Endoscopic reflectance spectrophotometry and visible light spectroscopy in clinical gastrointestinal studies. 1793 61

Adrenergic and serotonergic mechanisms alter human gut motor functions. Genotype variation influences phenotype. Our aim was to test the hypothesis that variation in genes that control these functions is associated with gastrointestinal (GI) motor functions in humans with functional GI disorders (FGID). A database of 251 people was assembled by combining genotype data with measurements of gut transit and gastric volumes. Genetic variations evaluated were: alpha(2A) adrenergic (C-1291G), alpha(2C) (Del 332-325), 5-HT transporter (SLC6A4) and GNbeta3 (C825T). We sought associations between motor function or disease groups and genotypes, adjusting for age, gender and body mass index. Among 251 participants, 82 were healthy, 20 with irritable bowel syndrome (IBS) with mixed bowel habit, 49 with constipation-predominant IBS, 67 with diarrhoea-predominant IBS and 33 with functional dyspepsia. For all candidate genes, there was no significant association between motor function and wildtype vs non-wildtype gene status. There were significant interactions between genotype and motility phenotype, specifically GNbeta3 and alpha(2A) and gastric emptying at 4 h. Borderline associations were noted for SCL6A4 and alpha(2A) and postprandial gastric volume, and for alpha(2C) and gastric emptying at 2 h. We conclude that genotype variation may affect gastric motor functions in different FGID phenotypes. However, these candidate genes account for only a limited amount of the variance in gastric function of patients with FGID.
 ...
PMID:An exploratory study of the association of adrenergic and serotonergic genotype and gastrointestinal motor functions. 1797 Oct 28

The concept of the gut forming the centre of an integrated gut-brain-energy axis - modulating appetite, metabolism and digestion - opens up new paradigms for drugs that can tackle multiple symptoms in complex upper gastrointestinal disorders. These include eating disorders, nausea and vomiting, gastroesophageal reflux disease, gastroparesis, dyspepsia and irritable bowel syndrome. The hormones that modulate gastric motility represent targets for gastric prokinetic drugs, and peptides that modify eating behaviours may be targeted to develop drugs that reduce nausea, a currently poorly treated condition. The gut-brain axis may therefore provide a range of therapeutic opportunities that deliver a more holistic treatment of upper gastrointestinal disorders.
 ...
PMID:Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders. 1830 13

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.
 ...
PMID:Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases. 1834 99

Against the background that what one eats affects the gastrointestinal tract (G.I T), the role of diet and dietary habits including fibres, food additives and preservatives on the aetiology of gastric cancers, colorectal cancers and other G.I disorders in the tropics are herein reviewed. Carcinomas of the gut believed to be on the decline in the developed countries have plateaued and increasing cases are being reported in the tropics. Africa and Nigeria in particular, with little or no cases previously are currently experiencing patterns of incidence similar to those of the Western Hemisphere. All these developments are premeditated by the nature of diets and dietary factors contained therein. Some of these factors contain chemical carcinogens, irritants as additives or preservatives, high cholesterol, highly spiced foods, alcohol, nicotine, xanthines, caffeine, most of which provoke gastric acid secretions dyspepsia and heartburn, and they lack vegetables and dietary fibres known to protect the G.I tract against various diseases. The roles of dietary hygiene implicating certain microorganisms associated with G.I diseases like Helicobacter Pylori are also discussed. It presupposes that well articulated diet and proper dietary manipulations remain the cure for all diet induced G.I disorders while avoidance of such habits that predispose to them must be encouraged to ensure proper and healthy G.I T.
 ...
PMID:Diets/dietary habits and certain gastrointestinal disorders in the tropics: a review. 1837 11

Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03+/-1.35% vs. 11.38+/-2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03+/-1.35% vs. 2.60+/-0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.
 ...
PMID:Adaptive upregulation of gastric and hypothalamic ghrelin receptors and increased plasma ghrelin in a model of cancer chemotherapy-induced dyspepsia. 1845 14

The eosinophil-mast cell-neural pathway may be important in the pathophysiology of functional gastrointestinal disorders characterized by unexplained abdominal pain, disordered defecation, or meal-related discomfort. There is evidence that duodenal eosinophils are increased in functional dyspepsia, whereas mast cells are increased in the lower gut in irritable bowel syndrome, directly supporting a role for a hypersensitivity-type reaction in these disorders. The trigger may be a pathogen, food, or other allergen in the gut mucosa. This trigger may evoke eosinophils, mast cells, and other components to cascade to up-regulate serotonin release, with modulation of the enteric and central nervous systems, creating a vicious cycle. If correct, this theory suggests treatment should specifically target the eosinophil-mast cell pathway.
 ...
PMID:Functional gastrointestinal disorders and the potential role of eosinophils. 1849 26

Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including alpha2A (C-1291G), alpha2C (Del 332-325), GNbeta3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GNbeta3 was associated only with fasting GV; we did not detect associations between alpha2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GNbeta3 with fasting GV may explain, in part, the reported association of GNbeta3 with dyspepsia.
 ...
PMID:Candidate genes and sensory functions in health and irritable bowel syndrome. 1851 40

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for the management of various conditions, such as pain, fever, inflammation, cancer, or cardiovascular diseases. These drugs may induce injury throughout the gastrointestinal tract. NSAIDs are associated with diverse upper gastrointestinal adverse effects, including dyspepsia, erosions, peptic ulcer diseases and complications such as bleeding perforation. Established risk factors for these adverse effects include age, prior ulcer, types, doses and duration of NSAIDs, concurrent other NSAIDs administration, and the concomitant uses of corticosteroids or anticoagulants. Misoprostol, proton pump inhibitors, and cyclooxygenase-2 selective inhibitors have been used to reduce the risk of NSAID-associated upper gastrointestinal events. NSAID-induced enteropathy is more common than complications of the stomach and duodenum and is usually manifested by occult blood loss or hypoalbuminemia. Furthermore, NSAIDs induce small intestinal injuries causing gut barrier damage, and bacterial translocation that have been proposed to be associated with the burden of illness in decompensated chronic heart failure. However, the risk factors for NSAID-induced enteropathy and bacterial translocation, as well as its preventive measures, are not well documented.
 ...
PMID:[NSAID-induced gastroenteropathy]. 1907 9

Researching the functions of serotonin, or 5-hydroxytryptamine (5-HT), in the gut has helped define new 5-HT receptors, increased the understanding of the side effects of numerous drugs and, via development of drugs, brought relief to millions of people suffering from disorders such as gastroparesis, dyspepsia, constipation, diarrhoea, irritable bowel syndrome and cancer. However, safety issues associated with alosetron and tegaserod (key drugs that modulate 5-HT function) have brought 5-HT and gastrointestinal research to a crossroad--is it now too hard to develop drugs in this area or is there a way forward? In this review, I describe the background to 5-HT in gastrointestinal physiology and disease, and the actions of drugs that interact with 5-HT3 and 5-HT4 receptors. Future research directions include modulating 5-HT availability by inhibition of tryptophan hydroxylase, understanding the functions of receptors such as 5-HT2B, 5-HT7 and the recently described 5-HT3-receptor subunits, and investigating how receptors activated by other products of tryptophan catabolism interact with gastrointestinal functions of 5-HT.
 ...
PMID:5-hydroxytryptamine and the gastrointestinal tract: where next? 1908 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>