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)

It has been demonstrated that nitric oxide (NO) is a major inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter in the gastrointestinal (GI) tract. NO released in response to nerve stimulation of the myenteric plexus causes relaxation of the smooth muscle. NO is synthesized by the activation of neuronal NO synthase (nNOS) in the myenteric plexus. Released NO plays an important physiological role in various parts of the GI tract. NO regulates the muscle tone of the sphincter in the lower esophagus, pylorus, sphincter of Oddi, and anus. NO also regulates the accommodation reflex of the fundus and the peristaltic reflex of the intestine. Previous studies have shown that NOS inhibitors delay gastric emptying and colonic transit. The reduction of nNOS expression, associated with impaired local production of NO, may be responsible for motility disorders in the GI tract. There is accumulated evidence that dysfunction of NO neurons in the myenteric plexus may cause various GI diseases. These reports are reviewed and possible mechanisms of altered nNOS expression are discussed in this article. In particular, impaired nNOS synthesis of the myenteric plexus seems to be an important contributing factor to the pathogenesis of achalasia, diabetic gastroparesis, infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and Chagas' disease. Reduced NO release and/or nNOS expression are suspicious in a subset of patients with functional dyspepsia. Although the etiology of intestinal pseudo-obstruction remains unknown, it is conceivable that extrinsic denervation may upregulate nNOS expression, resulting in enhanced muscular relaxation and disturbed peristalsis. An animal model of colitis showed impaired nNOS expression in the colonic myenteric plexus. Antecedent infection may be associated with the impaired NO pathways observed in functional dyspepsia, colitis, and Chagas' disease.
 ...
PMID:Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract. 1276 83

Chronic gastroparesis and CIP are debilitating disorders that are difficult to treat with currently available therapies. Failure of proper migration and differentiation of enteric neurons or ICC can result from specific genetic mutations and lead to phenotypes of CIP with or without concomitant gastroparesis. Intestinal dysfunction in diabetes may reflect a depletion of NO production (and perhaps other neurotransmitters or modulators), which is manifest as a syndrome of gastroparesis, diarrhea, or constipation in individual patients. As the key molecular changes underlying these disorders are defined, clinicians will begin to understand their precise etiology and rational medical therapy may become possible. In the future, testable hypotheses regarding the etiology of other functional bowel disorders (e.g., functional dyspepsia, irritable bowel syndrome, and so forth) may be developed.
 ...
PMID:Diagnosis and treatment of chronic gastroparesis and chronic intestinal pseudo-obstruction. 1285 9

Gastric neuromuscular disorders encompass a spectrum of dysfunction in nerve and smooth muscle that includes gastric visceral hypersensitivity, gastric dysrhythmias, fundic dysfunction, antral hypomotility, and gastroparesis. Patients with each disorder may present with such vague dyspepsia symptoms as early satiety, upper abdominal discomfort, bloating, or nausea with or without vomiting. A careful history and physical examination may suggest a gastric neuromuscular disorder, but symptoms are nonspecific. Gastroparesis is the most severe form of neuromuscular dysfunction. Such reversible causes of gastroparesis as mechanical obstruction of the stomach and chronic mesenteric ischemia must be excluded. Gastroparesis, gastric dysrhythmias, and hypersensitivity may follow viral infection or be due to degenerative processes that affect the gastric enteric neurons, smooth muscle, or interstitial cells of Cajal. Commonly, the cause of these gastric neuromuscular disorders is unknown. An approach to the diagnosis and treatment of gastric neuromuscular disorders is reviewed, including dietary counseling, drugs, and medical devices.
 ...
PMID:Diagnosis and treatment of neuromuscular disorders of the stomach. 1286 63

Information on the utility of solid-phase gastric emptying studies (SPGES) in the evaluation of children with symptoms of upper gastrointestinal (GI) motor dysfunction is limited. This study was conducted to evaluate the impact of SPGES in the clinical management and outcome of children with upper GI symptoms suggestive of gastroparesis. The records of 45 children who underwent SPGES (31F; 3-17 years) were reviewed. All patients had GI symptoms suggesting gastroparesis. Patients were fed with Tc-99m-sulfur colloid-labeled chicken liver. Adult normal half-life (T1/2) values (F 103 +/- 14 minutes; M 66 +/- 13.6 minutes) were used. The relationships among symptoms, treatment, and outcome were evaluated. Of the 45 patients 9 had delayed, 16 had rapid, and 20 had normal gastric emptying. Six of 9 patients with delayed gastric emptying responded to cisapride. Four of 16 patients with rapid emptying were diagnosed with the dumping syndrome. Of the children with rapid gastric emptying, 87% were females. Twenty patients with normal emptying were diagnosed with gastroesophageal reflux (8), nonulcer dyspepsia (5), irritable bowel syndrome (2), Helicobacter pylori (1), lactose intolerance (1), eosinophilic gastroenteritis (1), duodenitis (1), and constipation (1). In patients who had SPGES for possible gastroparesis, 20% had gastroparesis, 36% had rapid gastric emptying, and 44% had normal gastric emptying. The high number of females in the rapid gastric emptying group might be secondary to normal adult female T1/2 values that were used. The practice of using adult normal T1/2 values in prepubertal girls may need to be revised. Patients with delayed gastric emptying responded to cisapride.
 ...
PMID:The impact of solid-phase gastric emptying studies in the management of children with dyspepsia. 1455 21

Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptors for metoclopramide; 5-HT4 receptors for levosulpiride) and ability to permeate the blood-brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood-brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood-brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/benefit ratio.
 ...
PMID:Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. 1487 Dec 77

The term 'Functional diseases' implies symptoms arising from an organ without overt pathology. However this is more apparent than real since inflammation often leaves changes in nerves and mucosal function only apparent with specialised techniques. Acute onset functional dyspepsia accounts for around 1/5 of functional dyspepsia and is characterised by early satiety, nausea, vomiting and weight loss. Impaired postcibal fundal accommodation may underlie some of these symptoms. Post infectious gastroparesis is much rarer and is associated with markedly delayed gastric emptying and antral hypomotility. Approximately 1/10 of IBS cases describe a post infectious onset. Post infectious IBS is typically of the diarrhoea-predominant type. Post inflammatory functional diseases tend to be associated with less psychological abnormalities and have a better prognosis than other functional diseases. There are isolated anecdotal reports of symptom response to anti-inflammatory treatments but larger controlled trials are needed.
 ...
PMID:Inflammation as a basis for functional GI disorders. 1532 5

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.
 ...
PMID:Basic and clinical pharmacology of new motility promoting agents. 1618 2

Electrogastrography (EGG) is the recording and the interpretation of gastric electrical activity. Recordings can be made from the gastrointestinal mucosa, serosa, or skin surface. Because of its ease of use, cutaneous EGG has gained wide acceptance. Many technical problems have been solved to obtain a good graph. The EGG is usually evaluated in terms of changes in the EGG waves amplitude and frequency. Deviations from the normal frequency of 3 cycles per minute may be referred to as brachy- or tachyarrhythmia. The clinical use of EGG has been most widely evaluated in patients with gastroparesis and functional dyspepsia. Scintigraphic gastric emptying is considered the gold standard test for evaluating gastroparesis and 13C-octanoate breath test an ideal alternative because does not use ionizing radiation. While gastric emptying evaluates the efficiency of gastric emptying, EGG focuses on the underlying myoelectrical activity. Using both EGG and 13C-octanoate breath test will be possible to detect many subset of dyspeptic patients and to understand the underlying problem.
 ...
PMID:Electrogastrography. 1645 27

Gastroparesis is the most severe form of gastric neuromuscular dysfunction along a continuum that encompasses gastric visceral hypersensitivity, gastric dysrhythmias, and pylorospasm. Gastroparesis may present with vague dyspepsia symptoms or with vomiting of undigested food and weight loss. A careful history and physical examination may suggest the diagnosis of gastroparesis, but symptoms associated with gastric neuromuscular disorders are non-specific. Gastroparesis in patients with diabetes, particularly type 2 diabetes, is more common than appreciated. If gastroparesis is confirmed, then reversible causes such as mechanical obstruction of stomach and chronic mesenteric ischemia must be excluded. ''Idiopathic'' gastroparesis may follow viral infections or be due to degenerative processes that affect gastric enteric neurons, smooth muscle, and/or interstitial cells of Cajal. An approach to the diagnosis and treatment of gastroparesis and gastric neuromuscular disorders is reviewed including dietary counselling and new medical devices.
 ...
PMID:Gastroparesis and neuromuscular disorders of the stomach. 1648 77

Gastrointestinal motility disorders encompass a wide array of signs and symptoms that can occur anywhere throughout the luminal gastrointestinal tract. Motility disorders are often chronic in nature and dramatically affect patients' quality of life. These prevalent disorders cause a tremendous impact both to the individual patient and to society as a whole. Significant progress has been made over the last 5 years in understanding the etiology and pathophysiology of gastrointestinal motility disorders. This clinical update will focus on seven of the most common gastrointestinal motility disorders (achalasia, non-achalasia esophageal motility disorders, dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, irritable bowel syndrome, and chronic constipation) with an emphasis on current treatment options and new therapeutic modalities.
 ...
PMID:Gastrointestinal motility disorders: an update. 1684 50


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