Showing papers by "S J Konturek published in 1983"

Protective action of omeprazole, a benzimidazole derivative, on gastric mucosal damage by aspirin and ethanol in rats.

Abstract: This study was designed to compare the influence of omeprazole, a potent inhibitor of H+/K+-ATP-ase involved in the final step of H+ secretion and prostaglandin (PG) I2 on the formation of gastric mucosal lesions induced by absolute ethanol or acidified aspirin (ASA). Omeprazole given intragastrically in both inhibitory (20 or 200 mumol/kg) and noninhibitory doses (2 mumol/kg) prevented dose dependently ASA- and ethanol-induced gastric lesions. The protective effect of omeprazole against ASA-induced lesions occurred when mucosal generation of PGs was completely suppressed and that against ethanol lesions when PG generation was increased above normal values. Pretreatment with PGI2 given intragastrically or subcutaneously both in inhibitory and noninhibitory doses prevented almost completely the formation of gastric mucosal lesions caused by both absolute ethanol and acidified ASA. This study indicates that omeprazole is capable of protecting gastric mucosa against ASA- and ethanol-induced injury and that this protection is unrelated to gastric inhibition or the biosynthesis of mucosal PGs.

Comparison of prostaglandin E2 and ranitidine in prevention of gastric bleeding by aspirin in man.

Abstract: This study was designed to compare the effect of oral administration of PGE2 (05 mg/kg) and ranitidine in larger (100 mg/dose) or smaller (10 mg/dose) doses on aspirin-induced gastric microbleeding and DNA loss determined chemically in gastric washings in eight healthy subjects Aspirin (05 g) given four times daily greatly increased the rate of gastric bleeding and DNA loss and pretreatment with PGE2 or ranitidine in larger doses almost completely prevented these changes Smaller non-antisecretory doses of ranitidine also reduced the rate of bleeding and DNA loss but to a lesser degree than PGE2 This study confirms that oral PGE2 has a protective action on gastric mucosa exposed to aspirin and that this property is also shared by ranitidine, a potent histamine H2-receptor antagonist

Prostaglandins and vagal stimulation of gastric secretion in duodenal ulcer patients.

Abstract: The effects of a stable prostaglandin (PG) E2 analog (15-R-15 methyl PGE2) and aspirin, a potent inhibitor of cyclooxygenase, on modified sham-feeding (MSF)-stimulated gastric secretion and serum gastrin and pancreatic polypeptide (PP) levels were measured in patients with duodenal ulcer. PGE2 analog given orally significantly reduced gastric acid and pepsin secretion and suppressed serum PP but not gastrin responses to MSF. Suppression of PG generation in the gastric mucosa did not influence the secretory or hormonal responses to MSF. This study shows that endogenous PGs are not involved in the control of vagally stimulated gastric secretion, but exogenous PGE2 analog is an effective inhibitor of such secretion and merits clinical evaluation in the treatment of duodenal ulcer.

Effect of enkephalin and naloxone on gastric acid and serum gastrin and pancreatic polypeptide concentrations in humans.

Abstract: The effects of a synthetic enkephalin analogue with prolonged opioid activity, D-ala-2-enkephalin (ala-enk) and naloxone given alone or in combination, on vagally, pentagastrin- and histamine-induced gastric secretion and plasma hormonal responses to vagal stimulation have been studied in healthy subjects. D-ala-2-enkephalin reduced basal gastric acid and pepsin secretion, and caused a dose-dependent inhibition of gastric secretory responses to modified sham-feeding and pentagastrin but not to histamine. It increased serum gastrin concentration and suppressed plasma pancreatic polypeptide response to modified sham-feeding. Naloxone alone at lower dose levels did not affect gastric secretion and plasma hormonal concentrations but at higher doses it reduced both basal and modified sham-feeding-induced secretion. When combined with ala-enk it reversed in part gastric secretory and plasma hormonal changes induced by this peptide during modified sham-feeding and pentagastrin stimulation. These results indicate that (1) stable enkaphalin analogue inhibits basal and vagally or pentagastrin-induced gastric secretion, and affects plasma hormonal response to vagal stimulation, at least in part, via activation of opioid receptors and (2) endogenous opioid substances may be involved in the stimulation of gastric secretion in man.

Comparison of the effect of omeprazole--a substituted benzimidazole--and ranitidine--a potent H2-receptor antagonist--on histamine-induced gastric acid secretion and the ultrastructure of canine parietal cells.

Abstract: Gastric acid secretion and mucosal biopsy findings in canine stomach were evaluated after administration of omeprazole or ranitidine with and without histamine stimulation. Pretreatment with omeprazole (1 mg/kg) or ranitidine (0.5 mg/kg) almost completely prevented subsequent stimulation of acid secretion by histamine (40 micrograms/kg-h). Only ranitidine pretreatment, however, prevented post-histamine morphological transformation of parietal cells into the active state after histamine. Omeprazole pretreatment did not prevent the development of canaliculi and the reduction in the number of tubulovesicles in parietal cells after histamine. This canalicular expansion was, however, only partial with microvilli tightly packed together. Injection of omeprazole or ranitidine during half maximal stimulation by histamine effectively inhibited gastric acid secretion both in gastric fistulas (GF) and Heidenhain pouches (HP), and transformed the morphology of parietal cells into the resting state. In addition, omeprazole treatment with and without histamine stimulation increased the number of parietal cells with condensed mitochondria. This study demonstrates that omeprazole and ranitidine, while both potent inhibitors of gastric acid secretion, affect the parietal cell ultrastructure in different ways. Omeprazole does not prevent the formation of canaliculi in histamine-stimulated cells. This underscores the relative value of morphometrical studies of parietal cells.

The use of carprofen, a non-steroidal antiinflammatory agent, in peptic ulcer diseases.

Abstract: The effects of carprofen (Roche), a nonsteroid antiinflammatory agent, on gastric secretion, serum gastrin level, electropotential difference (PD), gastric microbleeding, DNA loss, and the generation of mucosal prostaglandins (PGs) were examined in 20 duodenal ulcer patients with active ulcer (15 patients) or in remission (5 patients). Carprofen administered for one-week period at a therapeutic dose (300 mg/day) was well tolerated by all ulcer patients and no adverse effects were observed during or after treatment. Endoscopy performed after carprofen treatment showed complete ulcer healing in 9 out of 15 patients and no exacerbations were observed in the rest of patients. No significant changes were observed in basal or pentagastrin-induced secretion, PD, gastric microbleeding and DNA loss. The generation of PGE2, 6-keto-PGF1 alpha and thromboxane B2 was not affected by the treatment with carprofen. This study indicates that carprofen shows excellent gastrointestinal tolerance in ulcer patients, and it might be useful in the treatment of arthritic patients with peptic ulcer disease.

Inhibition of gastric secretion by fat and hypertonic glucose in the dog: role of gastric inhibitory peptide.

Abstract: 1. The gastric and intestinal phases of gastric secretion were selectively evoked by 'meals' of 5% liver extract or saline in five dogs provided with a special cannula that allowed complete separation of the stomach from the duodenum. 2. The gastric phase in response to liver extract administered into the stomach amounted to an increase in acid output equivalent to about 70% of the maximum output in response to histamine. There was also a significant rise in the concentration of gastrin but not of gastric inhibitory peptide (GIP) in the serum. 3. The addition of fat (2 or 4% corn oil) or glucose (20%) to this liver extract meal inhibited secretion of gastric acid by 50 and 30%, respectively, without affecting the concentration of gastrin or GIP in the serum. 4. The 5% liver extract in the duodenum stimulated an increase in gastric acid output amounting to about 40% of the maximum response to histamine. Serum gastrin and GIP levels were not affected. Additional fat (0.5-4.0%) or glucose (10-20%) reduced acid secretion under these conditions by between 50 and 80% without affecting serum gastrin concentrations. Significant increases in the concentration of GIP in the serum occurred in response to intraduodenal glucose (5%), and to fat at the highest dose used (4%). 5. Intraduodenal infusions of glucose (5-20%) significantly increased serum GIP levels. Gastric secretion in response to 5% liver extract in the stomach was significantly inhibited at the highest dose (10 or 20%) although gastrin release was unaffected. 6. These results show that intraduodenal fat and glucose both exhibit potent inhibitory effects on post-prandial gastric acid secretion but that there is no correlation between the changes in serum GIP concentration and the inhibition of gastric secretion under these conditions. 7. We conclude that GIP is unlikely to mediate fat-induced inhibition of gastric secretion, but it is still possible that it might be involved in the inhibition that occurs during intestinal perfusion with hypertonic glucose solutions.

Gastric cytoprotection by agents altering gastric mucosal sulfhydryl compounds: role of endogenous prostaglandins.

Abstract: Intragastric administration of cysteamine or diethyl maleate caused a dose-dependent reduction in the mean area of gastric lesions induced by absolute ethanol but failed to affect gastric ulcerations produced by acidified aspirin. Mucosal levels of glutathione were increased with cysteamine and reduced with diethyl maleate and did not correlate with the protective action of these agents on ethanol-induced mucosal lesions. The protective effects of these agents probably involved mucosal generation of prostaglandins, because pretreatment with indomethacin or aspirin, potent inhibitors of cyclooxygenase, partially prevented this protection. This study indicates that the mucosal generation of prostaglandins contributed, at least in part, to the gastric cytoprotection by agents altering mucosal contents of sulfhydryl compounds.