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)

To evaluate the effect of esophageal acid exposure on epithelial function, transmucosal potential, histopathological markers of acute tissue damage, and local nitric oxide production were examined in healthy volunteers treated with proton pump inhibitors (group I), patients with treated reflux disease (group II), and patients with untreated erosive reflux disease (group III). The participants were randomized to esophageal perfusion with either saline or HCl. Denominators of acute acid exposure were balloon cells in superficial layers and superficial densification. The nitric oxide concentrations in groups I to III increased from < 1, 10.0+/-10.0, and 20.6+/-19.9 ppb, respectively, to 300+/-80, 1360+/-1080, and 920+/-700 ppb after HCl infusion (P < 0.001). Inducible nitric oxide synthase was consistently expressed in the epithelium. Blood flow was lower among reflux patients but did not correlate with acid exposure or nitric oxide. Nitric oxide is formed following acid perfusion and predominantly in gastroesophageal reflux disease.
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PMID:Acid challenge to the esophageal mucosa: effects on local nitric oxide formation and its relation to epithelial functions. 1584 95

The objective of this study was to determine the incidence of gastroesophageal reflux disease (GERD) in bronchial asthma and the role of omeprazole for asthmatics with symptoms of GERD. Seventy asthmatics were screened for GERD by questionnaire. Patients with a history suggestive of GERD were confirmed by Bernstein test and further investigated for airway responsiveness to instillation of HCl in the esophagus. Symptom score, drug score and spirometric values were recorded initially and after four weeks of treatment with omeprazole. It was found that 74.28% of asthmatics had a history of GERD. Forty patients tested positive by Bernstein test and also showed airway responsiveness to instillation of HCl in the esophagus. There was a significant improvement in symptom scores (p < 0.001), drug scores (p < 0.001) and spirometric values (p < 0.001) after adding omeprazole to their treatment regimen. It was concluded that bronchial asthma and GERD are associated in the majority of patients (57.14%) and such patients are likely to improve with omeprazole.
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PMID:Gastroesophageal reflux disease in bronchial asthma and the response to omeprazole. 1599 72

Several studies have demonstrated that radiofrequency energy delivery at the gastroesophageal junction (the Stretta procedure) induces symptom relief in gastroesophageal reflux disease (GERD), although improvement of acid exposure on pH monitoring was usually limited. A role for decreased esophageal sensitivity has been suggested. Our aim was to evaluate the influence of Stretta on symptoms, acid exposure, and sensitivity to esophageal acid perfusion in GERD. Thirteen patients with established proton pump inhibitor (PPI)-dependent GERD (three males; mean age, 51+/-10 years) participated in the study. Before and 6 months after the procedure symptom score, pH monitoring and Bernstein acid perfusion test were performed. The latter was done by infusing HCl (pH 0.1) at a rate of 6 ml/min 15 cm proximal to the gastroesophageal junction for a maximum of 30 min or until the patients experienced heartburn. Results were compared by Student's t-test. Stretta procedure time was 51+/-4 min and no complications occurred. After 6 months, the symptom score was significantly improved (12.5+/-2.0 to 7.5+/-2.1; P<0.05), seven patients no longer needed daily PPI, and acid exposure was significantly decreased (11.6%+/-1.6% to 8.5%+/-1.8% of time pH<4; P<0.05). The time needed to induce heartburn during acid perfusion decreased from 9.5+/-2.3 to 18.1+/-3.4 min (P=0.01), and five patients became insensitive to 30-min acid perfusion, versus none at baseline (P=0.04). In conclusion, the Stretta procedure induces subjective improvement of GERD symptoms and decreases esophageal acid exposure. In addition, esophageal acid sensitivity is decreased 6 months after the Stretta procedure. The mechanism underlying this finding and its relevance to symptom control require further studies.
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PMID:Influence of radiofrequency energy delivery at the gastroesophageal junction (the Stretta procedure) on symptoms, acid exposure, and esophageal sensitivity to acid perfusion in gastroesophagal reflux disease. 1743 1

We investigated the effect of ecabet sodium (ecabet) on rat acute esophageal lesions induced by reflux of gastric juice. Ligation of both pylorus and fore-stomach induced the reflux of gastric juice, decreased the amount of mucus and formed hemorrhagic lesions in the esophageal mucosa. Intragastric injection of ecabet reduced the pepsin activity and prevented both the decrease of mucus amount and formation of lesions. Ecabet enhanced the reduction in lesion formation induced by omeprazole and ranitidine without a change in decreased acid concentration and pepsin activity. Digestion of mucosa and the reduction in mucus were prevented by ecabet in the everted HCl and pepsin treated esophageal sac. These results indicate that ecabet prevents esophageal lesions by inhibiting pepsin activity as well as by protecting mucus from degradation. These further implicate the therapeutic potential of ecabet for prevention/treatment of GERD, especially in combination with a proton pump inhibitor or H(2)-antagonist.
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PMID:Ecabet sodium prevents esophageal lesions induced by the reflux of gastric juice in rats. 1745 Apr 49

The effects of esophageal acidification on airway function are unclear. Some have found that the esophageal acidification causes a small increase in airway resistance, but this change is too small to cause significant symptoms. The aims of this study were to investigate the effects of esophageal acidification on multiple measures of airway function in chloralose-anesthetized cats. The esophagus was cannulated and perfused with either 0.1 M PBS or 0.1 N HCl at 1 ml/min as the following parameters were quantified in separate experiments: diameter of bronchi (n = 5), tracheal mucociliary transport rate (n = 4), tracheobronchial mucus secretion (n = 7), and lung function (n = 6). We found that esophageal acidification for 10-30 min decreased bronchial diameters primarily of the smaller low-resistance airways (10-22%, P < 0.05), decreased tracheal mucociliary transport (53%, 8.7 +/- 2.4 vs. 4.1 +/- 1.3 mm/min, P < 0.05), increased tracheobronchial mucus secretion (147%, 3.4 +/- 0.7 vs. 8.4 +/- 2.6 mg/10 min, P < 0.05), and caused no change in total lung resistance or dynamic compliance (P > 0.05). Considering that tracheal mucociliary transport rate is governed in part by mucus secretion, we concluded that the primary airway response to esophageal acidification observed is increased mucus secretion. Airway constriction may act to assist in rapid secretion of mucus and to increase the effectiveness of coughing while not affecting lung resistance or compliance. Given the buffering capabilities of mucus, esophageal acidification activates appropriate physiological responses that may act to neutralize gastroesophageal reflux that reaches the larynx, pharynx, or lower airways.
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PMID:Airway responses to esophageal acidification. 1792 8

Gastro-oesophageal reflux disease (GORD) is one of the most common causes of chronic cough; however, the mechanisms by which GOR initiates coughing are incompletely understood. We address the hypothesis that acidification of oesophagus acutely increases the cough reflex sensitivity in patients with GORD and chronic cough. Nine patients with GORD with chronic cough and 16 patients with GORD without cough were recruited. In a randomized double blind study, saline and acid (HCl, 0.1 mol L(-1)) were separately infused into oesophagus via naso-oesophageal catheter. Cough reflex sensitivity to inhaled capsaicin was determined immediately after completion of each infusion. Infusion of acid into oesophagus increased capsaicin cough reflex sensitivity in patients with GORD and chronic cough. In contrast, acid had no effect on the cough sensitivity in patients with GORD without cough. In a separate study, acid infusion into oesophagus did not affect the cough sensitivity in 18 healthy subjects. We conclude that acid in the oesophagus acutely increases the cough reflex sensitivity to capsaicin in patients with GORD and chronic cough. This phenomenon may contribute to the pathogenesis of cough due to GORD.
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PMID:Acidification of the oesophagus acutely increases the cough sensitivity in patients with gastro-oesophageal reflux and chronic cough. 1799 50

In a mature organism, the contact between various liquids and the laryngeal mucosa triggers lower airway protective responses (cough, swallowing, arousal). These laryngeal chemoreflexes (LCR) are essential for preventing aspiration. In contrast, previous studies showed that LCR are responsible for apnea and bradycardia in the neonatal mammal. Consequently, LCR, especially when triggered by acid gastrolaryngeal reflux, are deemed responsible for some apneas of prematurity and many life-threatening events of infancy and, probably, for some cases of sudden infant death syndrome. Recently, we have revisited LCR in full-term lambs during quiet sleep. Our results showed that the LCR triggered by HCl (pH 2), mimicking the acid component of an acid gastro-oesophageal reflux, were consistently like the mature LCR reported in adult mammals, without significant apneas and bradycardias (St-Hilaire 2005). These results prompted us to question whether premature birth alters LCR. Results show that LCR triggered in pre-term lambs by both saline and HCl are much more marked and clinically relevant than the ones observed in full-term lambs. Indeed, life-threatening responses to HCl, including repetitive apneas for more than 90 seconds, severe desaturation and bradycardia, were observed in 2 lambs at postnatal day 7 (D7). In addition, LCR were significantly blunted at D14. In conclusion, HCl can trigger potentially dangerous LCR in pre-term lambs at D7, suggesting that LCR in response to acid gastrolaryngeal refluxes are likely involved in some apnea/bradycardia/desaturation in pre-term infants, before they reach a post-conceptional age equivalent to full gestation.
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PMID:Laryngeal stimulation by an acid solution in the pre-term lamb. 1808 64

Esophageal hypersensitivity is one of the most common causes of noncardiac chest pain in patients. In this study, we investigated whether exposure of the esophagus to acid and other chemical irritants affected activity of thoracic spinal neurons responding to esophageal distension (ED) in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital sodium-anesthetized, -paralyzed, and -ventilated male rats. ED (0.2 or 0.4 ml, 20 s) was produced by water inflation of a latex balloon placed orally into the middle thoracic region of the esophagus. The chemicals were administered via a tube that was passed through the stomach and placed in the thoracic esophagus. To irritate the esophagus, 0.2 ml of HCl (0.01 N), bradykinin (10 microg/ml), or capsaicin (10 microg/ml) were injected for 1-2 min. Only neurons excited by ED were included in this study. Results showed that intraesophageal instillation of HCl, bradykinin, and capsaicin increased activity in 3/20 (15%), 7/25 (28%), and 9/20 (45%) neurons but enhanced excitatory responses to ED in 9/17 (53%), 8/15 (53%), and 7/11 (64%) of the remaining spinal neurons, respectively. Furthermore, intraesophageal chemicals were more likely to enhance the responsiveness of low-threshold neurons than high-threshold neurons to the esophageal mechanical stimulus. Normal saline (pH 7.4, 0.2 ml) or vehicle instilled in the esophagus did not significantly affect activity or ED responses of neurons. We conclude that enhanced responses of thoracic spinal neurons to ED by the chemically challenged esophagus may provide a possible pathophysiological basis for visceral hypersensitivity in patients with gastroesophageal reflux and/or esophagitis.
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PMID:Intraesophageal chemicals enhance responsiveness of upper thoracic spinal neurons to mechanical stimulation of esophagus in rats. 1818 15

We hypothesized that, in esophageal squamous epithelial cells, there are differences among individuals in the signal transduction pathways activated by acid reflux that might underlie the development of Barrett's esophagus. To explore that hypothesis, we immortalized nonneoplastic, esophageal squamous cells from patients with gastroesophageal reflux disease (GERD) with (NES-B3T) and without (NES-G2T) Barrett's esophagus and used those cells to study acid effects on MAPK proteins. During endoscopy in patients with GERD with and without Barrett's esophagus, we took biopsy specimens from the distal squamous esophagus to study MAPK proteins before and after esophageal perfusion with 0.1 N HCl. We used immunoblotting and Western blotting to study MEK1/2 phosphorylation at two activating sites (serines 217/221), MEK1 phosphorylation at an inhibitory site (threonine 286), and MEK1/2 activity. After acid exposure, both cell lines exhibited increased MEK1/2 phosphorylation at the activating sites; the NES-B3T cells had higher levels of MEK1 phosphorylation at the inhibitory site, however, and only the NES-G2T cells showed an acid-induced increase in MEK1/2 activity. Similarly, in the squamous epithelium of patients with GERD with and without Barrett's esophagus, acid perfusion increased MEK1/2 phosphorylation at the activating sites in both patient groups; the Barrett's patients had higher levels of MEK1 phosphorylation at the inhibitory site, however, and only the patients without Barrett's demonstrated an acid-induced increase in ERK1/2 phosphorylation. In esophageal squamous cell lines and biopsies from patients with GERD with and without Barrett's esophagus, we have found differences in MAPK pathways activated by acid exposure. We speculate that these differences might underlie the development of Barrett's metaplasia.
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PMID:Differences in activity and phosphorylation of MAPK enzymes in esophageal squamous cells of GERD patients with and without Barrett's esophagus. 1861 56

The excitatory amino acid glutamate plays an important role in the development of neuronal sensitization and the ionotropic N-methyl-d-aspartate receptor (NMDAR) is one of the major receptors involved. The objective of this study was to use a cat model of gastroesophageal reflux disease (GERD) to investigate the expression of the NR1 and NR2A subunits of NMDAR in the vagal and spinal afferent fibers innervating the esophagus. Two groups of cats (Acid-7D and PBS-7D) received 0.1 N HCl (pH 1.2) or 0.1 M PBS (pH 7.4) infusion in the esophagus (1 ml/min for 30 min/day for 7 days), respectively. NR1 splice variants (both NH(2) and COOH terminals) and NR2A in the thoracic dorsal root ganglia (DRGs), nodose ganglia (NGs), and esophagus were evaluated by RT-PCR, Western blot, and immunohistochemistry. Acid produced marked inflammation and a significant increase in eosinophil peroxidase and myeloperoxidase contents compared with PBS-infused esophagus. The NR1-4 splice variant gene exhibited a significant upregulation in DRGs and esophagus after acid infusion. In DRGs, NGs, and esophagus, acid infusion resulted in significant upregulation of NR1 and downregulation of NR2A subunit gene expression. A significant increase in NR1 polypeptide expression was observed in DRGs and NGs from Acid-7D compared with control. In conclusion, long-term acid infusion in the cat esophagus resulted in ulcerative esophagitis and differential expressions of NR1 and NR2A subunits. It is possible that these changes may in part contribute to esophageal hypersensitivity observed in reflux esophagitis.
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PMID:Alterations in N-methyl-D-aspartate receptor subunits in primary sensory neurons following acid-induced esophagitis in cats. 1897 10


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