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)

In the last 20 years considerable progress has been achieved--among others--in motility associated disorders, in chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease) and in the treatment and prophylaxis of bleeding from esophageal varices. The motility associated diseases achalasia, functional dyspepsia, irritable bowel syndrome and intestinal pseudoobstruction can be better treated now with drugs which either promote or inhibit motility. In chronic-inflammatory bowel diseases controlled studies have defined the role of salazosulfapyridine, 5-aminosalicylic acid, glucocorticoids, azathioprine and metronidazole. The bleeding from esophageal varices is handled nowadays successfully with a combination of mechanical treatment (sclerosing and banding) and lowering the portal pressure by vasoactive substances or the somatostatin analogue octreotide. The prophylaxis of bleeding with noncardioselective betablockers is also introduced on the base of controlled trials.
 ...
PMID:[Gastroenterology. I: General gastroenterology]. 949 75

The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine-extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.
 ...
PMID:Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection. 1111 84

This paper describes a 6-year-old Simmental bull with diabetes mellitus. The animal was referred to our clinic because of severe weight loss and chronic indigestion. Clinical examination revealed markedly disturbed general condition, impaired forestomach function and polyuria. There was aciduria, glucosuria and ketonuria. The most important biochemical findings were severe hyperglycemia, markedly increased activities of hepatic enzymes and severe metabolic acidosis. Plasma concentrations of insulin, insulin-like growth factor-I, thyroxine and 3,5,3'-triiodothyronine were lower than normal, whereas those of glucagon were higher than normal. Based on these findings, a diagnosis (secondary) diabetes mellitus was made. The bull was slaughtered and histological examination revealed mixed cell pancreatitis with severe degeneration of islet cells. Immunohistochemical examination of the pancreas showed that very few insulin-, glucagon-, somatostatin- and pancreatic polypeptide, insulin-like growth factor-I and adrenomedullin-producing islet cells were present.
 ...
PMID:[Diabetes mellitus caused by pancreatitis in a bull]. 1123 31

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.
 ...
PMID:Neuropeptides in the duodenal mucosa of chronic alcoholic heavy drinkers. 1137 57

Carcinoids are neuroendocrine tumours that rarely originate in the biliary tract. We report a case of gallbladder carcinoid associated with cholelithiasis extending to hepatic segments IV and V. The mass was detected by ultrasound in a 71-year-old-man investigated for recurrent right upper quadrant pain irradiating to the back and associated with dyspepsia. Cholecystectomy, locoregional lymphadenectomy and 4th and 5th hepatic segment resection were performed. The patient underwent chemotherapy and was also treated with somatostatin analogues. Despite this, he died after 12 months. We stress the rarity and aggressive behaviour of gallbladder carcinoid.
 ...
PMID:Gallbladder carcinoid: a case report. 1293 5

The authors report the case of a 26-year-old woman, with a palpable abdominal mass, dyspepsia, pain and weight loss. These symptoms were caused by a non-functioning or biologically inactive neuroendocrine tumour (BINT), weighing 510 g and located in the tail of the pancreas. The treatment opted for was a surgical resection consisting in a distal pancreatectomy. The results of the operation were satisfactory and the woman is now alive and in good health, without recurrence, after 7 years. The authors then go on to analyse the concept of non-functioning neuroendocrine tumours and the problems relating to their symptoms, location and nature. These tumours, which arise, from the pancreatic islet cells, fail to produce a clinical syndrome owing to insufficient peptide production or insufficient release, or concurrent secretion, of inhibitory peptides by the tumour or production of biologically inactive molecular forms of the peptides (without clinical effects). The value of tumour markers and the indications and type of surgery are also discussed according to the different patterns of tumour spread (local, locoregional and metastatic disease). It is stressed that a complete surgical resection is the only curative treatment for these tumours. Encouraging results have been recently obtained by adjuvant treatment with somatostatin analogues, chemotherapeutic agents and/or inteferon.
 ...
PMID:[Non-functioning neuroendocrine tumor of the pancreas: report of a clinical case and review of the literature]. 1458 17

Functional gastrointestinal disorders are characterised by central and peripheral physiological changes, associated with psychological factors. Successful drug development has been hindered by lack of adequate characterisation of the nature of symptoms and their physiological and psychological correlates. Animal models of chronic stress are lacking. High levels of drug safety are now demanded for treating non-life threatening conditions. Once close to market, patient pressure groups, health care providers and insurers, government, and the internet can all influence a drug's success. Serotonin-modifying drugs have been the main recent focus of development, with mixed results. Cisapride has been withdrawn because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists have been developed on the questionable assumption that they modify visceral sensation in patients. Problems have arisen with alosetron being associated with ischaemic colitis and a high incidence of constipation. The 5-HT4 agonists have their major effect on inducing peristalsis, and may modify gut secretion and sensory function. Tegaserod and prucalopride show promise in patients with constipation and related symptoms. 5-HT1 agonists may play a role in treating functional dyspepsia, partly by improving impaired gastric accommodation to a meal. Antidepressants, often found to be clinically beneficial in these disorders, also affect serotonin metabolism. Past successes, such as loperamide or the somatostatin analogue octreotide, involved targeting end organ receptors influencing motor function or secretion. Modifying sensory function is much more challenging. Future research with novel compounds need to keep these recent lessons in mind.
 ...
PMID:Pharmacological treatment of irritable bowel syndrome--from concept to sales. 1614 96

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.
 ...
PMID:Effects of itopride hydrochloride on plasma gut-regulatory peptide and stress-related hormone levels in healthy human subjects. 1671 77

The distribution and density of gastric endocrine cells in Balb/c mice bearing CT-26 carcinoma cells were studied immunohistochemically employing specific antisera against serotonin, somatostatin, glucagon, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP). The animals were divided into two groups, a non-implanted sham group and a CT-26 carcinoma cell-implanted group. Samples were collected from two regions of the stomach (fundus and pylorus) at 28 days after implantation of the medium or the CT-26 cells (1x10(5) cells/mouse). Five of the 6 types of immunoreactive (IR) cells were identified, with only the hPP IR cells not being detected. The regional distribution of the gastric endocrine cells in the CT-26 implanted group was similar to that of the non-implanted sham group. However, the endocrine cells were significantly decreased in the CT-26-implanted group as compared to those of the non-implanted sham group. Serotonin- and somatostatin-IR cells in the fundus and pylorus , and gastrin- and CCK-8-IR cells in the pylorus of the CT-26 implanted groups were significantly decreased compared to those of the sham group. In addition, glucagon-IR cells were restricted only to the fundus of the sham animals. hPP-IR cells were not detected in either the T-26 implanted- or the non-implanted group. Since endocrine cells are the anatomical units responsible for the production of gut hormones, a change in their density may reflect a change in their capacity to produce such hormones. Implantation of the tumor cell mass induced severe quantitative changes in gastric endocrine cell density, an abnormality which may contribute to the development of gastrointestinal symptoms, such as anorexia and indigestion, frequently encountered in cancer patients.
 ...
PMID:Changes in gastric endocrine cells in Balb/c mice bearing CT-26 carcinoma cells: an immunohistochemical study. 1721 38

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


<< Previous 1 2 3 Next >>