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Biomedical subjects

W Obtulowicz

Publications and source records attributed to W Obtulowicz.

At least 19 recordsLinked to original sources
PubMed1993

Effects of ebrotidine on aspirin-induced gastric mucosal damage and blood flow in humans.

Nonsteroidal anti-inflammatory agents (NSAIDs) such as aspirin (ASA) damage the gastric mucosa both in normal subjects and in arthritic patients. The aim of this study was to investigate the protective action of a new H2-receptor antagonist, ebrotidine, in the prevention of ASA-induced acute mucosal injury in the stomach of healthy volunteers. In a double-blind randomized crossover study 10 male volunteers received treatment with either placebo plus ASA (500 mg) or ebrotidine (800 mg) plus ASA twice daily for 3 days with 10 days' washout period between treatments. The mean number of gastric erosions seen at endoscopy after treatment with ebrotidine plus ASA (2.0 +/- 0.3) was significantly lower than that after placebo plus ASA (3.7 +/- 0.2). This reduction in lesion core by ebrotidine was accompanied by a significant increase in gastric blood flow (by 15% in corpus and 26% in antrum), by a rise in transmucosal potential difference (by 12%), and by a decrease of mucosal microbleeding. Ebrotidine afforded substantial protection from ASA-induced injury to the gastric mucosa, and this was accompanied by increase of the mucosal blood flow. We conclude that ebrotidine provides mucosal protection for patients taking NSAIDs.

Adult↗
PubMed1991

Effects of nocloprost on gastric functions in man.

Previous studies in animals and humans demonstrated that nocloprost, a stable prostaglandin E2 analogue, shows very high gastroprotective potency, relatively weak gastric inhibitory activity, and low systemic bioavailability after oral administration. In this study the effects of nocloprost on gastric acid secretion and intraluminal pH and on gastric emptying and plasma gastrin levels were determined in humans. Nocloprost at doses of 50 and 100 micrograms was ineffective, but at a dose of 200 micrograms it reduced the response to pentagastrin significantly and that to a peptone meal by 30-50% and abolished plasma gastrin response without affecting the rate of gastric emptying. Nocloprost given at a dose of 100 micrograms three times daily 30 min before the major meals (breakfast, lunch, and dinner) did not affect intragastric pH significantly as monitored by continuous intraluminal pH-metry. We conclude that nocloprost does not affect gastric acid secretion or intraluminal pH when applied at a dose (50-100 micrograms) that is gastroprotective and that is proposed for peptic ulcer therapy. A higher dose (200 micrograms) of nocloprost causes moderate gastric acid inhibition and suppression of plasma gastrin release without affecting gastric emptying or causing any side effects.

Adult↗
PubMed1990

Cholecystokinin in the inhibition of gastric secretion and gastric emptying in humans.

Cholecystokinin (CCK) is known to inhibit gastric acid secretion and gastric emptying but its physiological role in the inhibition of gastric functions is not settled. In this study performed on 16 young male subjects, gastric acid secretion and emptying rate were determined after intragastric administration of 8% peptone meal alone or in combination with intravenous infusion of graded doses of CCK-8 (5-80 pmol/kg.h) or with addition of vegetable oil to meal without or with pretreatment with loxiglumide, a specific CCK antagonist. CCK-8 infusion at lower dose (5 pmol/kg.h) was ineffective but at higher doses (20-80 pmol/kg.h) it resulted in a significant reduction in acid output by 39 and 43% and a decrease in gastric emptying from 54% to 40 and 22%, respectively. Pretreatment with loxiglumide abolished almost completely the inhibition of both gastric acid and gastric emptying by CCK-8. Fat added to peptone meal reduced gastric acid secretion by 42-65% and decreased gastric emptying to 24-32%. The pretreatment with loxiglumide tended to reduce fat-induced inhibition of gastric acid secretion and gastric emptying but the difference in the inhibition of gastric functions between the tests without and with loxiglumide was not significant. This study provides evidence that exogenous CCK administered at pharmacological doses is a potent inhibitor of gastric acid secretion and gastric emptying and probably acts via specific CCK receptors. In contrast, fat induces inhibition of gastric acid secretion and gastric emptying that cannot be fully attributed to hormonally acting CCK.

Adult↗
PubMed1987

Effects of protective drugs on gastric alkaline secretion in man.

This study was designed to determine the effects of sucralfate, De-Nol, and Maalox 70 on gastric HCO3 secretion in 34 healthy humans. Alkaline secretion was measured after pretreatment with ranitidine to abolish H+ secretion, using a constant perfusion-aspiration system and back-titration of the perfusates to the original pH 6.0. Luminal release of PGE2 was also measured in the gastric perfusates. Addition of sucralfate or De-Nol resulted in increments of gastric HCO3 secretion, reaching about 45% and 59%, respectively, of the maximal HCO3 response to 16,16-dimethyl PGE2 (dmPGE2). The highest response to Maalox 70 reached about 21% of dmPGE2 maximum. These effects of sucralfate, De-Nol, and Maalox 70 were accompanied by a significant increase in luminal release of PGE2. Pretreatment with atropine reduced basal and, in part, sucralfate-, De-Nol-, and Maalox 70-induced alkaline secretion, whereas pirenzepine did not affect this secretion. Aspirin reduced the release of PGE2 by about 80% and suppressed almost completely the gastric HCO3 response to sucralfate, De-Nol, and Maalox 70. This study provides evidence that sucralfate, De-Nol, and Maalox 70 stimulate gastric alkaline secretion via a prostaglandin-dependent mechanism.

16,16-Dimethylprostaglandin E2↗
PubMed1984

Effect of meciadanol on gastric secretion and aspirin-induced gastric mucosal injury in humans.

The aim of this study was to assess the effects of a newly synthesized flavonoid, meciadanol, on gastric secretion and on aspirin-induced gastric mucosal injury in healthy humans. In vitro experiments have shown that meciadanol (INN proposed) inhibits histidine decarboxylase in gastric cells. In our study meciadanol did not affect either basal or pentagastrin-stimulated gastric acid secretion or pepsin secretion and did not produce any endoscopic or histological changes in the stomach or duodenum. Meciadanol prevented aspirin-induced microbleeding and aspirin-induced DNA loss, suggesting that gastric mucosal histamine is involved in the mucosal injury caused by aspirin.

Adult↗
PubMed1984

Generation of prostaglandins in gastric mucosa of patients with peptic ulcer disease: effect of nonsteroidal antiinflammatory compounds.

Human fundic mucosa generates various prostaglandins (PGs), particularly PGE2, and tromboxanes. This generation appears to be significantly lower in gastric ulcer patients than in duodenal ulcer patients or normal subjects. Nonsteroidal antiinflammatory compounds (NOSAC), such as aspirin or indomethacin, greatly reduce the PG biosynthesis and cause mucosal damage, including mucosal erosions and hemorrhages observed at endoscopy, increased gastric microbleeding and DNA loss. In contrast, paracetamol or carprofen, a novel NOSAC, fails to affect mucosal generation of PGs and does not influence gastric mucosal integrity. This study indicates that endogenous PGs may be involved in the pathogenesis of gastric ulcer and that normal generation of mucosal PGs is essential for the mucosal integrity.

Adult↗
PubMed1983

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

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.

Action Potentials↗
PubMed1982

Effect of carprofen and indomethacin on gastric function, mucosal integrity and generation of prostaglandins in men.

The effects of indomethacin and carprofen on gastric secretion, serum gastrin level, electropotential difference, gastric microbleeding, DNA loss, mucosal blood flow and the production of mucosal prostaglandins (PGs) were investigated in a double-blind cross-over study in 18 healthy volunteers after one week of treatment. We did not observe any significant changes in basal and pentagastrin-stimulated gastric secretory parameters, serum gastrin level and electro-potential difference before and after treatment with these drugs. Mucosal blood flow was significantly reduced following indomethacin treatment. The most pronounced differences were found in endoscopic score studies of gastric mucosa. After indomethacin all subjects developed multiple erosions, submucosal haemorrhages, and half of them showed diffuse antral erythema. These effects were accompanied by a significant increase in both gastric microbleeding and DNA loss, and significant decrease in the production of PGE2. We concluded that carprofen, in contrast to indomethacin, did not alter gastric mucosal integrity and production of PGE2. This study indicates that the gastric mucosal damage by non-steroid anti-inflammatory compounds (NOSAC) depends upon the suppression of PGE2 biosynthesis, and that endogenous PGE2 is involved in the control of mucosal blood flow and mucosal integrity.

Adult↗
PubMed1981

Distribution of prostaglandins in gastric and duodenal mucosa of healthy subjects and duodenal ulcer patients: effects of aspirin and paracetamol.

The distribution of mucosal PGE2-like activity was determined by bioassay technique in the body and antrum of the stomach and in the duodenum of healthy subjects and duodenal ulcer patients before and after administration of aspirin, paracetamol, or histamine. In healthy subjects, the oxyntic, antral and duodenal mucosa was found to be capable of generating large amounts of PGE2, which were not significantly different from those found in duodenal ulcer patients. No correlation was found between the generation of PGE2 and gastric acid secretory status or serum gastrin level. Aspirin-and to a much lesser extent, paracetamol-caused a dramatic reduction in the ability of the gastric mucosa to biosynthesis PGE2 and this was accompanied by marked side-effects and injury to the gastric mucosa. Administration of histamine caused small but significant reduction in the biosynthesis of PGE2 but it was accompanied by marked mucosal damage. This study indicates that the gastric and duodenal mucosa is capable of generating PGE2-like activity which may be involved in the mechanism that protects the mucosa against the damage caused by aspirin.

Acetaminophen↗
PubMed1980

Comparison of ranitidine and cimetidine in the inhibition of histamine, sham-feeding, and meal-induced gastric secretion in duodenal ulcer patients.

The effects of ranitidine, a new H2-receptor antagonist which does not contain an imidazole ring, and cimetidine have been determined on histamine, meal-induced gastric acid secretion, and serum gastrin levels in duodenal ulcer patients. Compared with cimetidine, ranitidine was found to be about eight times more potent an inhibitor of histamine-induced secretion and four to five times more potent an inhibitor of sham-feeding, and real feeding induced acid secretion without effecting serum gastrin levels.

Adult↗
PubMed1980

Effects of pirenzepine and atropine on gastric secretory and plasma hormonal responses to sham-feeding in patients with duodenal ulcer.

The effects of atropine and pirenzepine on sham-feeding stimulated gastric secretion and serum gastrin and pancreatic polypeptide levels have been studied in 12 patients with duodenal ulcer. Both atropine and pirenzepine caused a dose-dependent decrease in acid and pepsin secretion induced by sham-feeding. Serum gastrin response to sham-feeding was negative and it was enhanced by atropine but suppressed by pirenzepine. Plasma pancreatic polypeptide level, which was markedly increased by sham-feeding, was abolished both by atropine and pirenzepine. This study shows that pirenzepine is a more selective inhibitor of gastric secretory and serum hormonal responses to sham-feeding than atropine and that it may be a useful tool for studying the cholinergic innervation of the oxyntic glands and the G-cells in man.

Adult↗
PubMed1979

Cephalic phase of gastric secretion in healthy subjects and duodenal ulcer patients: role of vagal innervation.

In 10 healthy subjects and 25 duodenal ulcer patients, gastric acid and pepsin and serum gastrin responses to cephalic-vagal stimulation induced by modified sham-feeding (MSF) were studied before and after vagotomy and atropinisation and compared with those to maximal stimulation with pentagastrin. When the MSF-induced peak acid output was normalised as a percentage of peak response to pentagastrin it was about 62% in healthy subjects and 66% in duodenal ulcer patients. Serum gastrin concentration was not changed significantly by modified sham-feeding either in normal subjects or in duodenal ulcer patients. Truncal vagotomy completely abolished gastric acid and pepsin responses to MSF in duodenal ulcer patients. Atropine almost completely suppressed gastric acid and pepsin responses to MSF in healthy subjects and reduced those in duodenal ulcer patients by about 62%. The combination of the modified sham-feeding and pentagastrin infusion resulted in augmentation of the acid output in duodenal ulcer patients but not in healthy subjects. This study shows that the cephalic phase results in a potent gastric acid and pepsin stimulation which is not accompanied by any change in serum gastrin concentration either in healthy subjects or duodenal ulcer patients and which is abolished by vagotomy and suppressed by atropine.

Adult↗
PubMed1976

Effect of growth hormone-release inhibiting hormone on hormones stimulating exocrine pancreatic secretion.

The nature and extent of growth hormone-release inhibiting hormone (GH-RIH, somatostatin)-induced inhibition of pancreatic secretion of bicarbonate and protein, an index of enzyme secretion, were studied by administration of exogenous secretin or cholecystokinin (CCK) and of a number of stimulants for endogenous release of these hormones in fasted pancreatic fistula dogs with and without an infusion of GH-RIH. The results of this study show that GH-RIH inhibits the pancreatic fluid and bicarbonate secretion induced by duodenal acidification and exogenous secretion. The kinetic analysis shows that the interaction between GH-RIH and secretin affecting pancreatic bicarbonate secretion possesses the characteristics of competitive inhibition. GH-RIH does not change the pancreatic protein response to exogenous CCK, but profoundly inhibits pancreatic response to a variety of the endogenous stimulants of CCK release, including duodenal perfusion of sodium oleate, amino acid mixture, or feeding of a peptone meal. We conclude that GH-RIH is a very potent inhibitor of the endogenous release of CCK from the intestinal mucosa and inhibits competitively the action of secretin but not CCK on the exocrine pancreatic secretion.

Animals↗
PubMed1976

Comparison of amino acids bathing the oxyntic gland area in the stimulation of gastric secretion.

This study was undertaken to compare the ability of L- and D-isomers of amino acids bathing the oxyntic gland area to stimulate acid secretion in conscious dogs with Heidenhain pouch (HP), gastric fistula (GF) and pancreatic fistula (PF). Acid outputs from HP were determined by an intragastric titration method when amino acid solutions were perfused into HP at various concentrations, pH values, and distention pressures. Only L-isomers of all natural amino acids were found to stimulate acid secretion, whereas D-isomers of amino acids tested were completely inert in this respect. The comparison of the secretagogue activity of amino acids shows that L-histidine among essential amino acids and glycine among nonessential amino acids exhibited the strongest stimulation of acid outputs, reaching, respectively, 52 and 40% of the maximal response to histamine. Decreasing the pH of L-histidine solution perfused into HP in sequential order from 5.0 to 1.0 resulted in a stepwise reduction of acid output, falling at pH 1.0 to about 40% of the peak response achieved at pH 5.0. Local irrigation of HP by 2% xylocaine and intravenous infusion of atropine (100 mug per kg per hr) or metiamide (2.9 mg per kg per hr) reduced but did not abolish HP response to chemical stimulation and the pH dependency of this response. We conclude that only L- and not D-isomers of amino acids bathing the oxyntic gland area stimulate acid secretion by a local, gastrin-independent mechanism sensitive to distention pressure and pH.

Amino Acids↗
PubMed1975

Chemical stimulatory mechanism in gastric secretion.

1. The serum gastrin level, gastric mucosal blood flow and acid secretion from the canine Heidenhain pouch have been measured in response to the introduction of bovine serum albumin, pepsin-digested albumin, an amino acid mixture, liver extract and mannitol used as control. 2. Distention of the Heidenhain pouch with mannitol or albumnin at pH 5-0 produced a similar pressure-related increase of acid secretion reaching a peak of only 10 percent of the maximal response to histamine. Pepsin-digested albumin was capable of producing larger acid outputs than undigested albumin. The highest acid output, attaining about 80 percent of the maximal response to histamine, was obtained with liver extract both before and after exhaustive dialysis to remove all the amino acids and short peptide fragments. An amino acid mixture containing all essential amino acids was also found to stimulate acid secretion but a lesser degree than liver extract. 3. This concluded that it is not the intact protein but the products of its digestion, the polypeptides and free amino acids, which are potent chemical stimulants of acid secretion from the oxyntic gland area. Since the serum gastrin level was not changed during acid secretion induced by peptic digests bathing the oxyntic gland area, the mechanism of chemical stimulation appears to be gastrin-independent. 4. The response to chemical stimulation by peptic digests can be greatly potentiated by combining this with distention of the oxyntic gland area. Topical application of xylocaine or atropine causes a marked decrease of Heidenhain pouch response to peptic digests, suggesting a possible neural reflex component in the mechanism of chemical stimulation of the oxyntic gland area. 5. When the pH of the liver extract in the Heidenhain pouch was gradually decreased in sequential order from 5-0 to 1-0, this resulted in a pH-related decrease in acid secretion and in the mucosal blood flow falling to the basal level at pH 1-0. Exogenous secretion given in graded doses from 0-5 to 8-0 u./kg. hr caused a small but dose-related inhibition of acid response to liver extract accompanied by a decrease of mucosal blood flow but without any significant change in the serum gastrin level. 6. The results indicate that the chemical stimulation of the oxyntic gland area by peptic digests is capable of inducing acid secretion by a local, gastrin-independent, partially neural reflex mechanism; sensitive to pH, pressure and secretin.

Albumins↗
PubMed1975

Characteristics of gastric inhibition by acidification of oxyntic gland area.

1. Gastric acid responses to the test meals were measured in the Heidenhain pouch, gastric and pancreatic fistula dogs, using the intragastric titration method, and monitoring the rate at which a solution of 1-0 N-NaOH had to be added to maintain the pH of the gastric content constant at pre-selected values ranging from 5-0 to 1-0. In this way the pH profile of the gastric acid and pepsin responses to a liver extract meal kept in the Heidenhain pouch or gastric fistula as well as to exogenous stimuli such as histamine, pentagastrin or Urecholine could be determined. 2. A liver extract meal adjusted to pH 5-0 produced a potent and pressure-related stimulation of acid secretion from the Heidenhain pouch without any change in secretion from the main stomach and pancreas or in the serum concentration of immuno-assayable gastrin. 3. Graded decrease of the liver extract meal pH to below 5-0 resulted in the pH-dependent inhibition of gastric acid output, which at pH 1-0 was only about 30% of the value attained at pH 5-0. Acid secretion from the Heidenhain pouch induced by exogenous stimuli such as histamine, pentagastrin or Urecholine also showed gradual decrease when the pH of the pouch content was decreased in sequential order from 5-0 to 1-0. This pH-dependent inhibition was accompanied by an increase in pepsin secretion. 4. The pH-dependent inhibition of the Heidenhain pouch response to the liver extract meal was not altered by topical application of a local anaesthetic and atropine or by the intravenous infusion of large doses of atropine, secretin or metiamide, which were shown to cause a marked inhibition of the main stomach response to the liver meal. 5. The results indicate that there is a local and gastrin-independent inhibition mechanism of gastric acid secretion activated by an acidified meal making contact with the oxyntic gland area.

Animals↗