Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrointestinal prokinetics promote or increase the coordination of the gut wall contractions leading to enhancement of propulsive motility and, consequently, caudal displacement of luminal contents. Currently, they are considered drugs of choice for the treatment of upper gastrointestinal tract functional motor disorders such as those associated with gastrooesophageal reflux disease, chronic dyspepsia, gastroparesis (idiopathic or secondary to other diseases) and acute or chronic idiopathic intestinal pseudo-obstruction. The aim of the present review is to give an outline of the pharmacology of currently available prokinetics and of novel drugs endowed with gastrointestinal prokinetic action that require further pharmacological and/or clinical testing. The novel drugs include recent generations of benzamide and non-benzamide 5-HT4 receptor agonists, motilin receptor agonists, and inhibitors of nitric oxide synthase. Furthermore, based on our improved knowledge of the role of 5-HT in emesis and gastrointestinal motility, the therapeutic potential of potent mixed 5-HT4 agonists--5-HT3 antagonists in the control of cytotoxic-drug-induced emesis and associated gut motor disturbances will be discussed. Lastly, a section of this review deals with the colon as a possible target for the action of prokinetics.
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PMID:Recent advances in the pharmacology of gastrointestinal prokinetics. 893 12

The motor control of the lower esophageal sphincter (LES) is critical for normal swallowing and emesis, as well as for the prevention of gastroesophageal reflux. However, there are surprisingly few data on the central organization and neurochemistry of LES-projecting preganglionic neurons. There are no such data in ferrets, which are increasingly being used to study LES relaxation. Therefore, we determined the location of preganglionic neurons innervating the ferret LES, with special attention to their relationship with gastric fundus-projecting neurons. The neurochemistry of LES-projecting neurons was also investigated using two markers of "nontraditional" neurotransmitters in vagal preganglionic neurons, nitric oxide synthase (NOS), and dopamine (tyrosine hydroxylase: TH). Injection of cholera toxin B subunit (CTB)-horseradish peroxidase (HRP) into the muscular wall of the LES-labeled profiles throughout the rostrocaudal extent of the dorsal motor nucleus of the vagus (DMN) The relative numbers of profiles in three regions of the DMN from caudal to rostral are, 43 +/- 5, 67 +/- 11, and 113 +/- 30). A similar rostrocaudal distribution occurred after injection into the gastric fundus. When CTB conjugated with different fluorescent tags was injected into the LES and fundus both labels were noted in 56 +/- 3% of LES-labeled profiles overall. This finding suggests an extensive coinnervation of both regions by vagal motor neurons. There were significantly fewer LES-labeled profiles that innervated the antrum (16 +/- 9%). In the rostral DMN, 15 +/- 4% of LES-projecting neurons also contained NADPH-diaphorase activity; however, TH immunoreactivity was never identified in LES-projecting neurons. This finding suggests that NO, but not catecholamine (probably dopamine), is synthesized by a population of LES-projecting neurons. We conclude that there are striking similarities between LES- and fundic-projecting preganglionic neurons in terms of their organization in the DMN, presence of NOS activity and absence of TH immunoreactivity. Coinnervation of the LES and gastric fundus is logical, because the LES has similar functions to the fundus, which relaxes to accommodate food during ingestion and preceding emesis, but has quite different functions from the antrum, which provides mixing and propulsion of contents for gastric emptying. The presence of NOS in some LES-projecting neurons may contribute to LES relaxation, as it does in the case of fundic relaxation. The neurologic linkage of vagal fundic and LES relaxation may have clinical relevance, because it helps explain why motor disorders of the LES and fundus frequently occur together.
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PMID:Organization and neurochemistry of vagal preganglionic neurons innervating the lower esophageal sphincter in ferrets. 1113 58

Activation of esophageal mechanosensors excites neurons in and near the central nucleus of the solitary tract (NSTc). In turn, NSTc neurons coordinate the relaxation of the stomach [i.e., the receptive relaxation reflex (RRR)] by modulating the output of vagal efferent neurons of the dorsal motor nucleus of the vagus (DMN). The NSTc area contains neurons with diverse neurochemical phenotypes, including a large population of catecholaminergic and nitrergic neurons. The aim of the present study was to determine whether either one of these prominent neuronal phenotypes was involved in the RRR. Immunohistochemical techniques revealed that repetitive esophageal distension caused 53% of tyrosine hydroxylase-immunoreactive (TH-ir) neurons to colocalize c-Fos in the NSTc. No nitric oxide synthase (NOS)-ir neurons in the NSTc colocalized c-Fos in either distension or control conditions. Local brain stem application (2 ng) of alpha-adrenoreceptor antagonists (i.e., alpha1-prazosin or alpha2-yohimbine) significantly reduced the magnitude of the esophageal distension-induced gastric relaxation to approximately 55% of control conditions. The combination of yohimbine and prazosin reduced the magnitude of the reflex to approximately 27% of control. In contrast, pretreatment with either the NOS-inhibitor NG-nitro-l-arginine methyl ester or the beta-adrenoceptor antagonist propranolol did not interfere with esophageal distension-induced gastric relaxation. Unilateral microinjections of the agonist norepinephrine (0.3 ng) directed at the DMN were sufficient to mimic the transient esophageal-gastric reflex. Our data suggest that noradrenergic, but not nitrergic, neurons of the NSTc play a prominent role in the modulation of the RRR through action on alpha1- and alpha2-adrenoreceptors. The finding that esophageal afferent stimulation alone is not sufficient to activate NOS-positive neurons in the NSTc suggests that these neurons may be strongly gated by other central nervous system inputs, perhaps related to the coordination of swallowing or emesis with respiration.
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PMID:Noradrenergic neurons in the rat solitary nucleus participate in the esophageal-gastric relaxation reflex. 1271 55

Infantile hypertrophic pyloric stenosis (IHPS) is a condition affecting infants in the first few months of life. The condition is manifested by persistent vomiting and is caused by a hypertrophied muscle obstructing the gastric outlet. The condition is treated by pyloromyotomy. The incidence is 1-8/1000 births and varies among different populations. The etiology of IHPS is unknown, but both genetic and environmental factors are thought to contribute to the disease. Genetic linkage analysis has so far localized five loci that could harbor genes contributing to IHPS. The only gene implicated in IHPS is the nitric oxide synthase gene (NOS1), in which a single nucleotide polymorphism (rs41279104) in the promoter region has been associated with the disease in 16 patients. In this study, we examined an association of this SNP in 54 familial and 28 sporadic cases with IHPS, and compared the results with normal controls using univariate and multiple logistic regression analysis. We could not confirm any association between the analyzed SNP and infantile hypertrophic pyloric stenosis.
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PMID:No association between a promoter NOS1 polymorphism (rs41279104) and Infantile Hypertrophic Pyloric Stenosis. 1985 41

Lead (Pb), a ubiquitous and potent neurotoxicant, induces several neurophysiological and behavioural changes, while Pb alters the function of multiple organs and systems, it primarily affects the central nervous system. In human adults, encephalopathy resulting from Pb intoxication is often characterized by sleeplessness, poor attention span, vomiting, convulsions and coma; in children, Pb-induced encephalopathy is associated with mental dullness, vomiting, irritability and anorexia; diminished cognitive function resulting in a mental deficit has been also observed during Prolonged exposure to Pb. Pb can produce oxidative stress, disrupt the blood-brain barrier and alter several Ca(2+)-dependent processes, including physiological processes that involve nitric oxide synthesis on central nervous system in development and adult animals. This review summarizes recent evidence showing that Pb can interfere with the production of nitric oxide and can disrupt the function of nitric oxide synthase. Lead interferes with nitric oxide-related physiological mechanisms, and Pb neurotoxicity may affect processes involved in learning and memory.
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PMID:Lead neurotoxicity: effects on brain nitric oxide synthase. 2252 9

Diabetic gastroparesis is defined as delayed gastric emptying without mechanical obstruction in the setting of diabetes. Symptoms range from mild bloating to severe vomiting episodes and can result in frequent hospitalizations and poor quality of life. It is suspected that diabetic gastroparesis is underdiagnosed due to its similar presentation to other conditions such as gastroesophageal reflux disease. The pathogenesis of diabetic gastroparesis remains unclear, but proposed mechanisms include vagal dysfunction, hyperglycemia, interstitial cells of Cajal network disturbances, loss of neural nitric oxide synthase expression in the myenteric plexus, and oxidative stress. Current management for diabetic gastroparesis focuses on dietary and lifestyle changes as well as improved glycemic control. Limited options for medical therapies are available that include prokinetic and antiemetic medications. Metoclopramide is the only FDA-approved medication for the treatment of gastroparesis. Metoclopramide improves symptoms of gastroparesis although extended treatment presents challenges such as decreased efficacy over time and increased risks for adverse events. We summarize the current knowledge of the pathophysiology of diabetic gastroparesis and review current and investigational treatments for diabetes gastroparesis.
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PMID:Diabetic gastroparesis: An overview of pathogenesis, clinical presentation and novel therapies, with a focus on ghrelin receptor agonists. 3294 98

Inflammatory bowel disease (IBD) is an important chronic condition associated with the infection affecting the gastrointestinal tract (G.I.) in dogs. Several factors' viz. gastrointestinal tract lymphoid tissue (GALT), permeability defects, genetic, ischemic, biochemical, psychosomatic disorders, infectious and parasitic agents, dietary allergies, and adverse drug reactions are associated with inflammatory bowel disease. The most noticeable clinical signs are vomiting, diarrhea, changes in appetite, weight loss, anorexia, ascites and peripheral edema. Nitric oxide (NO), a pleiotropic free radical messenger molecule plays an immense role in playing mucosal inflammation in the intestine through activation of NO synthase enzyme (iNOS). The complex mechanism associated with inflammation in the G.I. tract is also correlated with the expression of iNOS, enzymatic activity, and NO production. NO exerts a beneficial role in maintaining epithelial permeability as well as the immune response in acute colitis. But the excessive production of NO causes adverse effects. In the review, the author suggests that a complex phenomenon is associated with competing biochemical pathways triggered by NO through the regulation of mucosal inflammation in inflammatory bowel disease. This review is a unique compilation about the role of NO in the pathogenesis of inflammatory bowel disease of the dogs.
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PMID:Unravelling of nitric oxide signalling: A potential biomarker with multifaceted complex mechanism associated with canine inflammatory bowel disease (IBD). 3313 37