Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric function and histology were investigated in 24 patients with untreated chronic renal failure. At endoscopy nine patients had oesophagitis, 12 patients were considered to have gastritis, and the duodenum appeared inflamed in 20 patients. Endoscopic biopsies were taken at standard sites in the stomach and duodenum; gastritis was found in all patients, and 17 patients had duodenitis. Stimulated acid secretion was impaired in seven out of 20 patients and acid hypersecretion was found in a further two patients. Pepsin output correlated well with acid output in these patients. Fasting serum gastrin levels were elevated in 12 of the 19 patients tested. Patients with atrophic gastritis had low acid outputs and hypergastrinaemia, and when extensive gastritis was present, the patients tended to have more severe renal failure and hyposecretion of acid. Three patients were studied again after regular haemodialysis or renal transplantation and were found to show marked endoscopic and histological improvement.
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PMID:Gastric function and histology in chronic renal failure. 37 52

Among 51 patients with refractory symptomatic reflux esophagitis seen during an 18-month period, 8 (16%) had undergone previous partial gastrectomy. Either Billroth II (n = 6) or Billroth I (n = 2) resection had been carried out for peptic ulceration 18 months to 30 years beforehand. Each patients was evaluated by symptom scoring, endoscopy, and 24-hour pH monitoring plus a 16-hour esophageal aspiration study, in which 2-hourly aliquots were measured for acid, pepsin, conjugated and unconjugated bile acids, and trypsin. After conversion to a 45 cm Roux-en-Y gastroenterostomy, symptom scoring and endoscopy were repeated at 6 to 12 months in all eight patients. Pepsin, acid, and unconjugated bile acids were seldom present in esophageal aspirates. Conjugated bile acids in concentrations up to 30 mmol/L and trypsin up to 428 micrograms/ml were found in cases of severe esophagitis, mostly during nocturnal rest. Esophagitis, heartburn, regurgitation, and bilious vomiting were eradicated by Roux-en-Y conversion, but other postgastrectomy symptoms (early satiety, dumping, epigastric pain, and diarrhea) were largely unchanged. Postgastrectomy esophagitis resistant to medical therapy seems likely to be caused by nocturnal exposure to trypsin and conjugated bile acids; it is well controlled by a 45 cm Roux-en-Y conversion.
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PMID:Evaluation and surgical correction of esophagitis after partial gastrectomy. 172 72

Fifty two patients with abnormal acid gastro-oesophageal reflux were studied by simultaneous oesophageal pH monitoring and continuous aspiration for 16 hours. Aspirates (from discrete two hour periods) were analysed for volume, pH, bile acids (conjugated and unconjugated), trypsin, and pepsin. The results were compared with pH changes and degree of oesophagitis. Patients with oesophagitis had greater acid reflux than those without, but patients with stricture and Barrett's oesophagus had similar acid reflux to those with uncomplicated erosive oesophagitis. Pepsin concentrations were highest in patients with stricture and Barrett's oesophagus particularly during nocturnal periods. Conjugated bile acids were detected in 75% of patients, mainly during the night, but only 2% of aspirates contained concentrations likely to be cytotoxic. Unconjugated bile acids were not detected, and trypsin was seldom found. Reflux oesophagitis is caused by acid and pepsin. Bile acids and trypsin are probably unimportant.
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PMID:Composition of gastro-oesophageal refluxate. 195 60

Pepsin and trypsin cause erosive, hemorrhagic lesions in our rabbit model of experimental esophagitis. Since the gastroduodenal contents of patients with reflux esophagitis may also contain bile salts, we used our model to determine the effect that a bile salt, taurodeoxycholate (TDC), would have on the esophageal mucosa when combined with either pepsin in an acid perfusate (pH 2) or trypsin in an alkaline perfusate (pH 7.5). Indexes of esophageal injury included gross appearance of the mucosa, microscopic examination, and mucosal barrier integrity as determined by permeability to hydrogen ion. We found that when 5 mM TDC was combined with pepsin (0.3 mg/ml), the gross and microscopic changes of esophagitis, as well as net hydrogen ion flux, were diminished when compared with those observed with pepsin exposure alone. When increasing concentrations of TDC (2 to 10 mM) were added to pepsin, the morphologic degree of injury as well as hydrogen ion flux decreased in a dose-dependent manner. In contrast, when 5 mM TDC was combined with trypsin (1000 U/ml) in the alkaline perfusate, the gross and microscopic changes of esophagitis and the net of hydrogen ion flux were increased when compared with either bile salt or trypsin alone. These effects were also dose dependent. These data demonstrate that bile salts present in the gastroduodenal contents of patients with reflux esophagitis have the capacity to modulate the effects of pepsin and trypsin on the esophageal mucosa.
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PMID:Taurodeoxycholate modulates the effects of pepsin and trypsin in experimental esophagitis. 392 39

In recent years, gastric acid has been shown to play a major role in the pathogenesis of reflux oesophagitis, though it remains possible that defective oesophageal mucosal resistance may also play some part. Abnormally prolonged and/or frequent exposure of the distal oesophagus to a pH of less than 4 is the major defect; this results from frequent gastro-oesophageal reflux, the impact of which is magnified in about half of the patients by slow oesophageal acid clearance. Abnormal oesophageal acid exposure increases in severity from endoscopy-negative reflux disease through worsening grades of reflux oesophagitis. Pepsin activity has been shown to be a major determinant of the aggressiveness of refluxate and, in turn, the full activity of gastric pepsin requires a pH below 3. Thus, gastric acid probably exerts a predominantly indirect effect on the pathogenesis of reflux oesophagitis by determining peptic activity. Although bile and other components of small intestinal juice can injure the oesophageal mucosa, these factors are apparently important only in the exceptional patient with very severe reflux disease. Gastric acid hypersecretion is probably also unimportant in the majority of patients. Peptic activity, and hence the aggressiveness of refluxate, are reduced markedly between pH 3 and 4. Achievement of this threshold, pH 3-4, in the daytime is important as, contrary to traditional beliefs, daytime reflux, triggered by food intake, is of the greatest importance in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Roles of gastric acid and pH in the pathogenesis of gastro-oesophageal reflux disease. 804 25

Normal human esophageal mucosa exhibits biphasic secretory responses to intraluminal stimuli in terms of PGE2 release with a decline under the impact of HCl and an increase in PGE2 release during mucosal exposure to HCl/Pepsin. PGE2 secretory patterns in patients with reflux esophagitis (RE) remain unknown. We have studied, therefore, luminal release of PGE2 in 28 patients with nonhealed and healed RE, and compared the obtained results with corresponding values recorded in controls. The rate of luminal release of PGE2 in nonhealed RE exhibited a monophasic patterns, i.e., significantly decreased both during mucosal exposure to HCl (2,273 +/- 444, vs. 3,655 +/- 600 pg/min, p = 0.025) and HCl/pepsin (1,271 +/- 244, vs. 3,655 +/- 600 pg/min. p = 0.003) as compared to its basal value. However, the rate of luminal PGE2 release in patients with nonhealed RE in basal conditions and during mucosal exposure to HCl was significantly higher than corresponding values in controls. Luminal release of PGE2 in patients with healed endoscopic esophagitis was significantly lower as compared to corresponding values recorded in patients with nonhealed endoscopic changes and in controls. In conclusion, (a) monophasic inhibitory responses of the esophageal mucosa to intraluminal HCl and HCl/pepsin solutions in patients with RE indicate a different pattern of mucosal secretory response to intraluminal stimuli; (b) inhibition of the rate of luminal release of PGE2 under the impact of HCl/pepsin may play a role in the development and/or progression of mucosal damage; and (c) the decline in the rate of luminal PGE2 release in healed RE indicates that its elevated value in active esophageal disease should be considered as an implication of mucosal damage induced by HCl/pepsin.
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PMID:Monophasic luminal release of prostaglandin E2 in patients with reflux esophagitis under the impact of acid and acid/pepsin solutions. Its potential pathogenetic significance. 858 96

Pepsin, acid and Helicobacter pylori are major factors in the pathophysiology of peptic ulcer disease and reflux oesophagitis. Ecabet sodium reduces the survival of H. pylori in the stomach and inhibits pepsin activity in the gastric juice of experimental animals. Here we have investigated the effects of ecabet sodium on some of the factors involved in the dynamics of the mucosal barrier, i.e. pepsins and mucins. This study used gastric juice obtained from 12 non-symptomatic volunteers and nine patients with reflux oesophagitis. Ecabet sodium significantly inhibited pepsin activity in human gastric juice, with a maximum inhibition of 78%. Pepsin 1, the ulcer-associated pepsin, was inhibited to the greatest extent. The ability of gastric juice to digest mucin was significantly inhibited by ecabet. As with gastric juice proteolytic activity, the inhibitory effect of ecabet on mucolysis was greater in gastric juice from patients with reflux oesophagitis than in that from controls. Ecabet sodium showed a positive interaction with gastric mucin, as assessed by an increase in viscosity. Thus ecabet sodium may reduce the aggressive potential of gastric juice towards the mucosa, which may be relevant in the treatment of reflux oesophagitis and peptic ulcer disease. In addition, it may strengthen the mucus barrier in peptic ulcer disease and gastritis.
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PMID:Mucosal protective effects of ecabet sodium: pepsin inhibition and interaction with mucus. 1125 80

Pepsin, a protease activated by gastric acid, is a component of the refluxate, yet the role of pepsin in the pathogenesis of reflux esophagitis has not been well studied. In the present study, we examined the effect of pepstatin, a specific inhibitor of pepsin, on acid reflux esophagitis. Acid reflux esophagitis was induced in rats by ligating both the pylorus and the forestomach for 3 or 4 hr. Pepstatin, ecabet Na (the anti-ulcer drug), and L-glutamine were administered intragastrically after the ligation. Pepstatin or ecabet Na, given intragastrically, significantly prevented esophageal lesions, even though they did not affect basal acid secretion in pylorus-ligated rats. Pepstatin significantly inhibited pepsin activity in vivo and in vitro, while ecabet Na inhibited this activity in vitro. By contrast, L-glutamine given intragastrically aggravated the lesions in a dose-dependent manner, but even in the presence of L-glutamine the development of esophageal lesions was totally prevented by coadministration of pepstatin or ecabet Na. L-Glutamine increased the pH of gastric contents to approximately 2.0, the optimal pH for the proteolytic activity of pepsin in vitro. In addition, intragastric administration of exogenous pepsin worsened the severity of esophageal damage. These results suggest that pepstatin is highly effective against acid reflux esophagitis, without influencing acid secretion, while L-glutamine aggravated these lesions by increasing the pepsin activity by shifting the intraluminal pH to the optimal pH range for proteolytic action. It is assumed that pepsin plays a major pathogenic role in the development of acid reflux esophagitis.
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PMID:Essential role of pepsin in pathogenesis of acid reflux esophagitis in rats. 1653 73

Experimental models for esophageal epithelium in vitro either suffer from poor differentiation or complicated culture systems. An air-liquid interface system with normal human bronchial epithelial cells can serve as a model of esophageal-like squamous epithelial cell layers. Here, we explore the influence of bile acids on barrier function and tight junction (TJ) proteins. The cells were treated with taurocholic acid (TCA), glycocholic acid (GCA), or deoxycholic acid (DCA) at different pH values, or with pepsin. Barrier function was measured by transepithelial electrical resistance (TEER) and the diffusion of paracellular tracers (permeability). The expression of TJ proteins, including claudin-1 and claudin-4, was examined by Western blotting of 1% Nonidet P-40-soluble and -insoluble fractions. TCA and GCA dose-dependently decreased TEER and increased paracellular permeability at pH 3 after 1 h. TCA (4 mM) or GCA (4 mM) did not change TEER and permeability at pH 7.4 or pH 4. The combination of TCA and GCA at pH 3 significantly decreased TEER and increased permeability at lower concentrations (2 mM). Pepsin (4 mg/ml, pH 3) did not have any effect on barrier function. DCA significantly decreased the TEER and increased permeability at pH 6, a weakly acidic condition. TCA (4 mM) and GCA (4 mM) significantly decreased the insoluble fractions of claudin-1 and claudin-4 at pH 3. In conclusion, acidic bile salts disrupted the squamous epithelial barrier function partly by modulating the amounts of claudin-1 and claudin-4. These results provide new insights for understanding the role of TJ proteins in esophagitis.
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PMID:Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins. 2161 16