[Nimesulide-induced hepatotoxicity].
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Aged↗
Biomedical subjects
J M Blas
Publications and source records attributed to J M Blas.
Adaptation of esophageal mucosa to acid- and pepsin-induced damage: role of nitric oxide and epidermal growth factor.
To study whether the esophageal mucosa was able to elicit mucosal adaptation, we induced esophageal damage by perfusing acidified pepsin in rabbits. Mucosal adaptation was induced by preexposing the esophageal mucosa to a mild irritant (acidified saline) for 60 min prior to acidified pepsin (strong irritant). Macroscopic and microscopic esophageal injury, cell proliferation, and mucosal barrier function (H+, K+, hemoglobin flux rates) were studied. Preexposure of the esophageal mucosa to acidified saline significantly decreased both the mucosal damage and the mucosal barrier dysfunction induced by acidified pepsin. The development of this phenomenon was nondependent on cell proliferation. Concomitant treatment with either the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine, or the perfusion of immunospecific EGF-receptor antibodies or tyrphostin-25, an inhibitor of the tyrosine kinase activities ligated to the intracytoplasmatic domain of the EGF receptor, during the preexposure period completely reversed the protection induced by acid. We conclude that the rabbit esophageal mucosa shows mucosal adaptation to acid and pepsin. The development of this phenomenon is fast, not dependent on cell proliferation, and dependent, at least in part, on nitric oxide and EGF-receptor-mediated mechanisms.
Adaptation, Physiological↗
[Evaluation of intravenous ranitidine and omeprazole effect on the 24-hour gastric ph-metry in duodenal ulcer hemorrhage].
BACKGROUND: The pharmacotherapy of bleeding peptic ulcer is directed to improve the environment of the bleeding point by keeping the gastric pH above the proteolytic range for pepsin. OBJECTIVE: To evaluate the best pharmacological approach to inhibit gastric acid secretion with current antisecretory drugs in patients with bleeding duodenal ulcers. METHODS: Forty-seven patients with bleeding duodenal ulcers were randomized to receive I.V.: I) Omeprazole: an initial bolus of 80 mg + perfusion of 3.3 mg/h; II) Omeprazole: an initial bolus of 80 mg + 40 mg/12 h; III) Omeprazole: 40 mg/8 h; IV) Ranitidine: perfusion of 12.5 mg/h; V) Ranitidine: 50 mg/4 h. Gastric acidity was measured and recorded by 24 h gastric pH monitoring. RESULTS: All types of treatment with omeprazole were superior to either continuous perfusion or intermittent bolus of ranitidine in increasing the pH for 24 h and reducing the % of time the gastric pH was below 4 and 6, and the number of time the gastric pH was below 4 for more than 5 min. There were no statistical differences between the different regimens of omeprazole, but continuous perfusion of ranitidine was superior to intermittent ranitidine bolus. CONCLUSIONS: Parenteral omeprazole is better than parenteral ranitidine in keeping the intragastric pH above the proteolytic range for pepsin in patients with bleeding duodenal ulcers.
Adolescent↗
Aspirin renders the oesophageal mucosa more permeable to acid and pepsin.
OBJECTIVE: To examine the effects of aspirin on the oesophageal mucosa and on acid- and pepsin-induced oesophagitis. DESIGN AND METHODS: The effects both of intraluminal (18 mg/ml) and of parenteral (100 mg/kg per h) aspirin on an in-vivo rabbit model of oesophagitis induced by acidified pepsin (pH 2) were studied. Oesophageal injury was assessed by macroscopic and microscopic scoring including the cell proliferation immunohistochemical parameter mib1. The mucosal barrier function was determined by hydrogen, potassium and haemoglobin flux rates. RESULTS: Acidified saline alone caused no damage, but the addition of aspirin induced mucosal barrier damage (P < 0.05). The exposure of the oesophageal mucosa to acidified aspirin and then acidified pepsin significantly increased mucosal injury and mucosal barrier dysfunction compared with control experiments (exposure to acidified saline and acidified pepsin). This damage was significantly (P < 0.05) reduced (> 40%) by prostaglandin cotherapy (prostaglandin E2) administered before acidified aspirin exposure. Mucosal damage was less severe (P < 0.05) when the oesophageal mucosa was exposed to a pH 6 aspirin solution. Parenterally administered aspirin also increased the oesophageal damage induced by acidified pepsin compared with control experiments, but the damage was 23% lower than that obtained with intraluminal aspirin. Cell proliferation studies showed a significant increase in the number of positive cells in those experiments with a higher degree of damage and in those treated with prostaglandins. CONCLUSION: Aspirin renders the oesophageal mucosa more permeable to acid and pepsin. These effects are in part pH-dependent and might be partially reversed by prostaglandin E2 cotherapy.
Acids↗