Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recorded esophageal alkaline exposure time (AET) in 52 patients with gastroesophageal reflux and in 20 control subjects to determine whether esophageal pH monitoring can measure reflux of bile acids and trypsin from the duodenum. Patients underwent a further 16-h study (divided into 2-h periods) in which AET was correlated with bile acid and trypsin concentrations in esophageal aspirates. Patients had greater nocturnal AET than controls (22.7 versus 0.9%, p = 0.005). Patients with a stricture had a greater AET than patients with erosive esophagitis (25.2 versus 13%, p less than 0.05). There was no relationship between esophageal bile acid concentrations and AET, and total bile acid concentrations were similar regardless of whether a 2-h period contained alkaline episodes. Esophageal bile acid concentrations were no different, in patients with a normal esophagus, esophagitis, stricture, or Barrett's esophagus. Trypsin was found in only 5% of aspirates, and could not be predicted by AET. We conclude that measurement of AET is not useful in the clinical evaluation of duodeno-esophageal bile reflux, and bile acids and trypsin are not important in the pathogenesis of reflux esophagitis.
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PMID:Bile acids and trypsin are unimportant in alkaline esophageal reflux. 155 3

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

Esophagitis after total gastrectomy has been associated with biliary and pancreatic reflux into the esophagus. The purpose of this study is to clarify the effect of FOY-305 on these factors in the esophagitis. We initially produced esophagitis in rats with total gastrectomy followed by an end-to-side esophago-jejunostomy (Billroth-II). After treatment of FOY-305 on post-operative day 7 in this model, esophageal washout samples were analyzed for increases in activity of trypsin and total bile acid concentration. FOY-305 completely inhibited increases of trypsin activity in 2 and 4 hr, and it significantly (P less than 0.05) reduced bile acid concentration in 4 hr after initiating treatment. In addition, we evaluated the injurious effect of trypsin and sodium taurocholate (Tc-Na) on isolated esophagus of rats by measuring released tyrosine in the medium and used it as an index of the degree of injury. Tc-Na (3-fold of enteral bile acid concentration) inflicted only a slight injurious effect with negligible tyrosine release increases, and it did not show synergistic action when concomitantly used with trypsin. However, trypsin clearly induced increased tyrosine release from the esophageal mucosa, and this effect was significantly (P less than 0.001) inhibited by FOY-305 (50 microM). These results indicate that trypsin is one of the important factors in the pathogenesis of reflux esophagitis after total gastrectomy, and FOY-305 exerts a therapeutic effect by eliciting an inhibitory action against trypsin activity.
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PMID:[Effect of FOY-305 on post-operative reflux esophagitis in rats (II). Analysis of mechanism in the pathogenesis of reflux esophagitis after total gastrectomy in rats]. 187 3

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

The morphology of esophageal mucosal damage induced by trypsin was investigated in an experimental model, where the rabbit esophagus was perfused in situ with a control solution (physiologic NaCl) and trypsin (1 mg/ml). The results indicate that trypsin has an adverse effect on esophageal mucosa. In light microscopy infiltration of leucocytes in the submucosa and later ulcerative changes in the mucosa were seen. Scanning electron microscopy showed detachment of superficial cells and later deeper lesions, displaying denuted intramucosal collagen bundles with erythrocytes. In transmission electron microscopy significant widening of the intercellular spaces could be seen. This suggests that in clinical situations trypsin refluxed from duodenum into stomach and further to esophagus has an adverse effect on esophageal mucosa and may have importance in the pathogenesis of clinical reflux esophagitis. Because of the relatively high pH-optimum trypsin may have importance only under nonacidic or alkaline conditions.
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PMID:Morphological alterations in tryptic esophagitis: an experimental light microscopic and scanning and transmission electron microscopic study in rabbits. 235 88

This review critically evaluates the gastroduodenal factors that may play a clinically relevant role in the pathogenesis of reflux esophagitis. The gastroesophageal pressure gradient is of obvious importance, but the role of gastric contraction/relaxation is poorly understood. The intragastric volume, as well as the factors that influence it, could theoretically play a role in gastroesophageal reflux (GER). For example, suppression of gastric emptying and gastric motility would be expected to increase GER, and treatment with gastrokinetic agents appears to provide symptomatic improvement. However, only a fraction of patients with GER have delayed gastric emptying, and there is no correlation between either subjective epigastric fullness or esophagitis on one hand and gastric emptying on the other hand. Gastric acid and pepsin, and possibly the hypersecretion of acid, play a pivotal role in reflux esophagitis, as demonstrated by the efficacy of the treatment with histamine H2 antagonists and antacids. Other important factors in experimental esophagitis are duodenogastric reflux, the presence of bile acids in the gastric contents, as well as trypsin if the pH is alkaline. It is suggested that these important findings may lead to novel therapeutic approaches of reflux esophagitis.
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PMID:Clinical relevance of gastroduodenal dysfunction in reflux esophagitis. 309 Jan 34

Esophagitis occurs in patients with excessive acid and/or alkaline gastroesophageal reflux. This observation prompted us to develop a continuously perfused in vivo rabbit esophageal model to examine the potential for different endogenous injurious agents to cause H+ back diffusion and morphologic evidence of esophagitis. We found that HCl at physiologic pH values did not break the mucosal barrier to H+ back diffusion or cause esophagitis. Bile salts at physiologic concentrations in both an acid or alkaline perfusate broke the mucosal barrier and caused H+ back diffusion, but failed to cause a morphologic injury consistent with clinical reflux esophagitis. Instead, proteolytic enzymes, such as pepsin in an acid environment and trypsin in an alkaline environment, caused a severe hemorrhagic erosive esophagitis consistent with that seen clinically. We feel new therapeutic strategies for the treatment of reflux esophagitis should be directed at proteolytic enzymes rather than only HCl or bile salts. Finally, we showed sucralfate to be a mucosal protectant against the acid-pepsin injury.
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PMID:Experimental esophagitis in a rabbit model. Clinical relevance. 309 Jan 35

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

Esophagitis is now recognized to occur in the absence of gastric acid. We have compared the potentially injurious effect of physiologic concentrations of trypsin, taurodeoxycholate, and pepsin at pH 7.5 using a continuously perfused rabbit esophagus model. Gross and microscopic esophagitis, tissue hemorrhage, and indexes of esophageal mucosal barrier function were assessed. Trypsin caused the most severe morphologic changes and hemorrhage, but only minimal disruption of the esophageal mucosal barrier. In contrast, taurodeoxycholate caused only minimal esophagitis and no hemorrhage, but caused extensive disruption of the esophageal mucosal barrier. Neither pepsin, at this alkaline pH, nor alkaline test solution alone (pH 7.5) caused esophageal injury by any criteria. These results show that the degree of esophageal mucosal barrier disruption cannot always be equated with the degree of morphologic injury, and that different components of the gastroduodenal contents may differ in their sites or mechanisms of esophageal injury. Finally, among the gastroduodenal contents we tested, trypsin was the most noxious agent in alkaline reflux esophagitis in terms of causing mucosal erosion, inflammation, and hemorrhage.
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PMID:Alkaline esophagitis: a comparison of the ability of components of gastroduodenal contents to injure the rabbit esophagus. 630 6

The esophageal mucosa maintains a barrier that is relatively impermeable to glucose, H+, and other small molecules. Injury of the mucosa causes disruption of this barrier, manifest initially by increased permeability to small molecules. In the stomach the mucosa is protected from gross ulceration in the presence of bile-induced H+ back diffusion (JH+) by increases in mucosal blood flow (Qm). Qm to the esophagus during injury has never been studied. We explored the possibility that esophageal Qm would increase as a compensatory reaction to early barrier disruption. Rabbits (2 to 4 kg) were anesthetized and the in situ esophagus was luminally perfused for two 1-hour periods with subulcerogenic concentrations of bile salts, pepsin, or trypsin in the presence (pH 2) or absence (pH 7) of acid. Qm was measured with 15 mu radioactive microspheres in nine experimental groups with a total of 62 rabbits. Changes in Qm were compared with changes in permeability of the esophageal barrier to glucose, Na+, and H+. When the mucosal barrier was broken by bile salts or trypsin at a neutral pH, no acid back diffusion occurred and barrier disruption was accompanied by dramatic increases in esophageal mucosal blood flow. In contrast, barrier disruption by bile salts, pepsin, or acid during pH 2 perfusions failed to elicit increases in Qm when significant JH+ (50 microEq/hr) occurred. These results demonstrate a loss in reactive regulation of esophageal Qm in the presence of significant JH+ that may contribute to the injury seen in acid reflux esophagitis.
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PMID:H+ back diffusion interferes with intrinsic reactive regulation of esophageal mucosal blood flow. 646 68


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