Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have focused on understanding the onset of gastroesophageal reflux disease by examining the mucosal response to the presence of acid in the esophageal lumen. Upon exposure to HCl, inflammation of the esophagus begins with activation of the transient receptor potential channel vanilloid subfamily member-1 (TRPV1) in the mucosa, and production of IL-8, substance P (SP), calcitonin gene related peptide (CGRP) and platelet activating factor (PAF). Production of SP and CGRP, but not PAF, is abolished by the neural blocker tetrodotoxin suggesting that SP and CGRP are neurally released and that PAF arises from non neural pathways. Epithelial cells contain TRPV1 receptor mRNA and protein and respond to HCl and to the TRPV1 agonist capsaicin with production of PAF. PAF, SP and IL-8 act as chemokines, inducing migration of peripheral blood leukocytes. PAF and SP activate peripheral blood leukocytes inducing the production of H(2)O(2). In circular muscle, PAF causes production of IL-6, and IL-6 causes production of additional H(2)O(2), through activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Among these, NADPH oxidase 5 cDNA is significantly up-regulated by exposure to PAF; H(2)O(2) content of esophageal and lower esophageal sphincter circular muscle is elevated in human esophagitis, causing dysfunction of esophageal circular muscle contraction and reduction in esophageal sphincter tone. Thus esophageal keratinocytes, that constitute the first barrier to the refluxate, may also serve as the initiating cell type in esophageal inflammation, secreting inflammatory mediators and pro-inflammatory cytokines and affecting leukocyte recruitment and activity.
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PMID:Viewpoints on Acid-induced inflammatory mediators in esophageal mucosa. 2110 19

Gastroesophageal reflux and intestinal distension have been described in survivors of congenital diaphragmatic hernia (CDH). Deficient enteric innervation demonstrated in experimental models is a likely explanation for these symptoms. This study aimed at further characterizing these anomalies and examining esophageal and intestinal motility in this condition. Pregnant rats received either nitrofen or vehicle on E9.5. Sections of E15, E18, and E21 esophagus and small bowel were stained for protein gene product 9.5, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase (NADPHd), and acetylcholinesterase (AChE). The proportion of neural tissue/muscle surface was measured and the NADPHd- and AChE-positive motor endplates (MEPs) were counted. E18 and E21 stomachs were stained for AChE, the ganglia were counted and measured. The peristalsis of the esophagus and small bowel was video recorded. The relative neural/muscle surface and the number of NADPHd- and AChE-positive MEPs were decreased on E15 and E18 in the esophagus and small bowel of embryos with CDH, but they tended to improve on E21. The number and the mean surface of stomach ganglia were smaller in E18 and E21 fetuses with CDH. Peristaltic movements were decreased in the esophagus and small bowel of animals with CDH. Deficient enteric innervation impaired gastrointestinal motility in experimental CDH. This could explain some long-term morbidity in the human condition.
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PMID:Enteric nervous system and esophageal-gastrointestinal motility in experimental congenital diaphragmatic hernia. 2368 64