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 acute enteritis in the postneonatal period with or without dyspepsia appeared with an incidence ranging from 18,9% to 27,6% during twenty years period (1956--1975) observations in a general children's autopsy material. Bacteriological and serological analysis may be of success and complete the pathologic-anatomical diagnoses. Infective enteritis often is accompanied by pneumonia and/or otitis media. The acute enteritis can always be detected as an important feature in regard to the cause of death. Most children die within less than twenty-four hours from hospital admission. The hemorrhagic, ulcerous and necrotic form of the enterocolitis predominate the perinatal and neonatal period, frequently combined with peritonitis and bowel perforation. Bacteriological examinations should be obtained. This form of the acute enteritis and enterocolitis of the newborns must be taken into consideration of the ileus symptoms differential diagnosis.
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PMID:[Value and incidence rate of the inflammation of the bowels in a general children's autopsy material during twenty years (author's transl)]. 64 88

Cisapride is a substituted benzamide compound that stimulates motor activity in all segments of the gastrointestinal tract by enhancing the release of acetylcholine from the enteric nervous system. Cisapride is administered orally in the treatment of gastro-oesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction syndromes and chronic constipation. In gastro-oesophageal reflux disease in both adults and children, cisapride provides symptomatic improvement and mucosal healing. Long term treatment with cisapride is effective in the prevention of relapse of oesophagitis. Cisapride improves gastric emptying rates and improves symptoms in patients with gastroparesis of various origins. Unlike domperidone and metoclopramide, long term administration of cisapride seems to result in persistently enhanced gastric emptying. Cisapride is also effective in improving symptoms in patients with functional dyspepsia. In comparative studies in patients with functional dyspepsia, cisapride was at least as effective as metoclopramide, domperidone, clebopride, ranitidine and cimetidine. Cisapride increases stool frequency and reduces laxative consumption in patients with idiopathic constipation. Severe cases of slow transit constipation seem refractory to cisapride. Clinical studies also indicate that cisapride might be effective in the treatment of chronic intestinal pseudo-obstruction, postoperative ileus, peptic ulcer and irritable bowel syndrome. Further clinical studies are warranted to define the role of cisapride in these conditions. The dosage of cisapride ranges from 5mg 3 times daily to 20mg twice daily. Cisapride is generally well tolerated, both during short and long term treatment. In children, cisapride is also well tolerated in doses of 0.2 to 0.3 mg/kg, 3 to 4 times daily.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A risk-benefit assessment of cisapride in the treatment of gastrointestinal disorders. 852 13

Acupuncture has been used for various gastrointestinal (GI) conditions. Voluminous data support the effect of acupuncture on the physiology of the GI tract, including acid secretion, motility, neurohormonal changes, and changes in sensory thresholds. Much of the neuroanatomic pathway of these effects has been identified in animal models. A large body of clinical evidence supports the effectiveness of acupuncture for suppressing nausea associated with chemotherapy, postoperative state, and pregnancy. Prospective randomized controlled trials have also shown the efficacy of acupuncture for analgesia for endoscopic procedures, including colonoscopy and upper endoscopy. Acupuncture has also been used for a variety of other conditions including postoperative ileus, achalasia, peptic ulcer disease, functional bowel diseases (including irritable bowel syndrome and nonulcer dyspepsia), diarrhea, constipation, inflammatory bowel disease, expulsion of gallstones and biliary ascariasis, and pain associated with pancreatitis. Although there are few prospective randomized clinical studies, the well-documented physiological basis of acupuncture effects on the GI tract, and the extensive history of successful clinical use of acupuncture, makes this a promising modality that warrants further investigation.
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PMID:Acupuncture for gastrointestinal and hepatobiliary disorders. 1010 29

Fedotozine [(1R)-1-phenyl-1-[(3,4,5-trimethoxy)benzyloxymethyl]-N,N- dimethyl-n-propylamine, (2S,3S-tartrate] is derived from the arylacetamide series. As with other compounds of this series, fedotozine is more or less selective of kappa(1)-opioid receptors and particularly for the kappa(1a)-receptor subtype, where it acts as an agonist. Pharmacological studies have shown that fedotozine exerts a peripheral antinociceptive action, comparable with that of other kappa-agonists. Its main effects have been demonstrated at the level of the afferent nerve pathways originating from the gut. Fedotozine alters the processing of visceral sensations along these pathways and hence, the perception of gut stimuli at the brain level. It modifies reflexes induced in various pathological conditions, like experimental inflammation of the gut, chemically-induced peritonitis or post-operative ileus. Fedotozine also decreases the nociceptive reflexes triggered by noxious gut distension in animals. In humans, fedotozine decreases the perception of gut distension, both in physiological and pathological conditions. Clinical trials undertaken in patients with functional digestive disorders, non-ulcer dyspepsia and irritable bowel syndrome, have shown that fedotozine relieves abdominal pain in these patients in 6-week treatments. kappa-Opioid receptors remain an interesting area for future development of new treatments for abdominal pain in patients with functional digestive disorders.
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PMID:Pharmacology and clinical experience with fedotozine. 1111 83

Cases in which mesenteric vessels lead to stenosis of the duodenum are very rare. Several cases have been reported of patients suffering from stenosis of the last third of the duodenum due to a malpositioning of the superior mesenteric artery or the left renal vein. We report a 78-year-old patient who was suffering from dyspepsia, pain in the upper abdominal region, nausea, and vomiting. The medical history revealed that the patient had undergone a subtotal gastrectomy according to Billroth II at the age of 19 because of similar complaints. In the last 20 years the patient had to be laparotomized several times for ileus of the small intestine. Now the patient presented abdominal complaints with nausea and pressure in the upper abdominal region. Assuming an efferent-loop syndrome and adhesions, the patient was laparotomized. We discovered malpositioning of the superior mesenteric vein, leading to stenosis of the superior part of the duodenum. In fact, 60 years ago surgeons performed a duodenojejunostomy, circumvening the stenosis of the duodenum. With a "delay of 60 years", we then performed a subtotal gastrectomy according to Billroth II. The postoperative course was uneventful; the patient had no complaints and increased in body weight. To our knowledge, this is the first time that a stenosis of the duodenum due to malpositioning of the superior mesenteric vein has been observed.
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PMID:[Superior mesenteric vein syndrome: a case of duodenal stenosis caused by atypical malposition of the superior mesenteric vein]. 1125 80

Kappa (kappa)-opioid receptor agonists are particularly effective analgesics in experimental models of visceral pain. Their analgesic effects are mediated in the periphery. The molecular targets involved include peripherally located kappa-receptors and possibly, at least for some nonpeptidic kappa-agonists, additional nonopioid molecular targets such as sodium channels located on primary sensory afferents. Overall, these properties are expected to be of therapeutic interest in various visceral pain conditions, including abdominal surgery associated with postoperative pain and ileus, pancreatitis pain, dysmenorrhea, labor pain and functional disorders such as irritable bowel syndrome or dyspepsia. The first kappa-agonists to be developed were brain-penetrating organic small molecules. Their development was eventually discontinued due to central side effects such as sedation and dysphoria attributed to kappa-receptors located behind the blood-brain barrier. New drug discovery programs are now geared towards the design of peripherally-selective kappa-agonists. So far, most of the organic molecule-based peripheral kappa-agonists have achieved limited peripheral selectivity and a practically insufficient therapeutic window to justify full development. These compounds have been used in a small number of clinical pilot studies involving visceral pain. Although encouraging, the clinical data available so far with this class of compounds are too limited and fragmented to fully validate the therapeutic utility of kappa-agonists in visceral pain. Additional clinical studies with safer kappa-agonists (i.e. with higher peripheral selectivity) are still required. The most suitable tools to address this question in the future appear to be the newly discovered class of tetrapeptide-based kappa-agonists, which have shown unprecedented levels of peripheral selectivity.
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PMID:Peripheral kappa-opioid agonists for visceral pain. 1505 26

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

Opioids have been used medicinally and recreationally for thousands of years. The clinical use of opioids for gastrointestinal conditions has been limited by central nervous system side effects. A new generation of peripheral opioid receptor ligands free of central nervous system side effects is being developed. Clinical trials with the peripherally acting mu opioid receptor antagonists' alvimopan and N-methylnaltrexone show promise for improving postoperative ileus- and opioid-induced constipation. Likewise, preliminary studies with the peripherally acting kappa opioid agonist fedotozine showed promise in the treatment of irritable bowel syndrome (IBS) and functional dyspepsia. Further studies are on hold presumably due to lack of efficacy in subsequent studies. However, clinical studies are underway for newer kappa opioid agonists such as asimadoline and ADL 10-0101.
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PMID:Peripheral opioids for functional GI disease: a reappraisal. 1669 67

Motilin is a hormone released by the endocrine cells of the duodenal mucosa during fasting to stimulate gastrointestinal motility. Ghrelin, the closest family member of motilin, was discovered 10 years ago from the rat stomach as the long-awaited endogenous ligand of the growth hormone secretagogue receptor. Ghrelin has now emerged as a multifunctional hormone with important effects on energy homeostasis but also on gastrointestinal motility. Like motilin, it induces hunger contractions in the fasting state and acts postprandially to accelerate gastric emptying. While the development of motilin agonists for the treatment of hypomotility disorders has been going on for more than 15 years, the development of ghrelin agonists is still in its infancy. The failure of the first generation of motilin agonists in clinical trials has been largely due to problems of desensitization and worsening of symptoms due to effects on gastric accommodation. These issues are being taken care of with the second generation of motilin agonists that are currently under evaluation. Ghrelin agonists have the same potential as motilin agonists to treat hypomotility disorders but their effects on appetite may even be a bonus to treat disorders such as functional dyspepsia while ghrelin's anti-inflammatory effects may make it superior to motilin to treat post-operative ileus. Nevertheless the important endocrine activities of ghrelin may result in side effects which are not encountered with motilin. Future studies will need to point out whether the motilin-ghrelin receptor family will make it as a new class of gastroprokinetics.
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PMID:Motilin and ghrelin as prokinetic drug targets. 1942 31

Management of functional gastrointestinal disorders is hindered by both poor efficacy and adverse effects of traditional pharmacological therapy. Herbal medicine may be an attractive alternative based on the perception of its 'natural' approach and low risk of side effects; however, the lack of standardization of drug components has limited the ability to perform rigorous clinical studies in Western countries. Japanese herbal medicine (JHM) is a standardized form of herbal medicine with regards to the quality and quantities of ingredients. While extensively studied and widely used in Asia, there is a paucity of data upon which physicians in other parts of the world may draw conclusions regarding the effectiveness of herbal medicine for gastrointestinal disorders. The aim of this study was to summarize the most recent developments in JHM for treatment of functional gastrointestinal disorders. Animal and human studies were systematically reviewed to identify published data of JHM used for treatment of gastrointestinal disorders. The herbal components of JHM were examined. Results describing the physiological and clinical effects of JHM were abstracted, with an emphasis on functional gastrointestinal disorders. JHM are associated with a variety of beneficial physiological on the gastrointestinal system. Patient-based clinical outcomes are improved in several conditions. Rikkunnshi-to reduces symptoms and reverses physiological abnormalities associated with functional dyspepsia, while dai-kenchu-to improves symptoms of postoperative ileus and constipation in children. This updated summary of JHM in the field of gastrointestinal disorders illustrates the potential for herbal medication to serve a valuable role in the management of patients with functional gastrointestinal disorders.
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PMID:Japanese herbal medicine in functional gastrointestinal disorders. 1956 4


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