Effect of misoprostol and antacids on gastric and duodenal mucosal enzyme activities in duodenal ulcer patients

The activities of 11 marker enzymes from the gastric and duodenal mucosa were determined in 15 patients with active duodenal ulcer disease before therapy, after 4 weeks of therapy with the prostaglandin E1 analogue misoprostol, 400 micrograms twice daily, and after another 4 weeks without any therapy. Another 15 patients were given a high-dose liquid antacid regimen. The activities were measured in homogenized material obtained with forceps through an endoscope. The healing rates of the two groups at 4 weeks were 53% and 80%, respectively. No changes in mucosal inflammation were noted during therapy. During treatment with misoprostol the activities in the descending duodenum of the membrane enzymes alkaline phosphatase, leucyl-beta-naphthylamidase, gamma-glutamyltransferase, and 5'-nucleotidase increased towards the values seen in normal controls. Despite a higher healing rate, no changes in the enzyme activities occurred in the group given high-dose antacid therapy. Four weeks after cessation of therapy the enzyme activities in the misoprostol group were not significantly different from the pretreatment values. In the biopsy specimens from the duodenal bulb the activities of monoamine oxidase fell during treatment with misoprostol and were restored to the pretreatment activity when therapy was stopped. In the stomach mucosa the enzyme activities were largely unchanged during treatment with both misoprostol and antacids. These results indicate that misoprostol and antacids have different mechanisms of action but may also suggest that the demonstrated enzymic changes are unrelated to the healing process.     

Effect of ranitidine on the content of glyceroglucolipids in gastric secretion of patients with gastric and duodenal ulcer

The glyceroglucolipids content of basal and pentagastrin-stimulated gastric secretion was measured in male patients with gastric (12) and duodenal (12) ulcer. Six patients in each group received twice daily for a period of 4 weeks 150 mg of ranitidine, whereas the other patients received placebo. The glyceroglucolipids output in the basal secretion of patients with gastric and duodenal ulcer before treatment was similar and increased 2.7-fold after pentagastrin stimulation. In all patients treated with ranitidine, the mean output of glyceroglucolipids after pentagastrin stimulation increased from 1.38 to 2.05 mumol/h (P less than 0.05). This increase, however, was more pronounced in the duodenal ulcer group than in the gastric ulcer patients. No change in glyceroglucolipids output was noted in the patients treated with placebo. The ratio of glyceroglucolipids to HCl increased significantly (P less than 0.02) only in the ranitidine-treated patients.     

Dynamics of gastric acid inhibition by ranitidine in duodenal ulcer patients

The dynamics of the inhibitory effect of ranitidine, a new H2-receptor antagonist, on histamine and pentagastrin-induced gastric secretion have been examined in duodenal ulcer patients. The inhibition by ranitidine of histamine-induced secretion was found to be competitive, whereas that of pentagastrin-induced secretion not competitive. Ranitidine was an effective inhibitor of pentagastrin-induced secretion for 8-12 h after administration. The availability of ranitidine, a powerful and long-acting inhibitor of gastric secretion, provides an opportunity of an alternative treatment from cimetidine for peptic ulcer and related diseases.     

Enzyme activities in the gastric mucosa in duodenal ulcer patients

In a series of 45 consecutive duodenal ulcer patients (DU) the activities of 10 marker enzymes from the brush border, basolateral membrane, mitochondria, and lysosomes were determined by analysis of homogenized material taken with biopsy forceps through an endoscope from the antral and body part of the stomach. They were compared with the enzyme activities determined in controls with similar types of gastritis but without any evidence of peptic ulcer disease. All the DU patients had gastritis in the antral mucosa. In the body part, about 30% had gastritis. In the antral mucosa of DU patients the activities of the membrane and lysosomal enzymes were mostly increased when compared with the controls. In the gastric body mucosa of DU patients the activities of the lysosomal enzymes were mostly increased, whereas most of the membrane enzymes showed unchanged activities when compared with the corresponding controls. Monoamine oxidase activities were decreased or unaltered in both regions in these patients. The finding of enzymatic changes in the gastric mucosa of DU patients gives further support to an altered mucosal metabolism in these patients.     

Effect of ranitidine,a new H2-antagonist,on gastric and pancreatic secretion in duodenal ulcer patients

The effects of a new H₂-receptor blocker, ranitidine, given intravenously (for comparison with cimetidine) or orally on gastric and pancreatic secretion have been studied in duodenal ulcer patients. Ranitidine appears to be several times more potent and a longer-acting inhibitor of gastric secretion than cimetidine. This H₂ blocker does not affect pancreatic bicarbonate and enzyme secretion.     

Influence of oral cimetidine and ranitidine on gastric emptying in active duodenal ulcer

The effect on gastric emptying of 400 mg cimetidine and two doses of ranitidine (150 and 300 mg) given orally was evaluated in 45 patients with endoscopically proved duodenal ulcer and in 28 healthy controls. Gastric emptying of a radiolabeled solid phase meal was assessed. Cimetidine was confirmed not to have any significant influence on gastric emptying in duodenal ulcer patients or in healthy subjects. The significant delay in gastric emptying observed with ranitidine was dose dependent, and at the same time more pronounced in patients with duodenal ulcer than in healthy subjects. Early ulcer healing was unrelated to the changes in gastric emptying elicited by the tested drugs.     

Effect of somatostatin on meal-induced gastric secretion in duodenal ulcer patients

The effect of somatostatin, a growth hormone release-inhibiting hormone (GH-RIH), on basal and meal-, pentagastrin-, or histamine-stimulated gastric acid and pepsin secretion was studied in six duodenal ulcer patients. Intravenous GH-RIH infused in graded doses ranging from 0.62 to 5.0 μg/kg/hr produced a dose-related inhibition of pentagastrin-induced acid secretion reaching about 15% of control level at the dose of 5.0 μg/kg/hr. Acid inhibition was paralleled by a decrease in the pepsin output and accompanied by a dosedependent reduction in serum growth hormone and insulin levels measured by radio-immunoassay. GH-RIH used in a single dose of 2.5 μg/kg/hr produced about 85% inhibition of acid secretion induced by a meal (measured by intragastric titration) accompanied by a significant decrease in serum gastrin and insulin levels. The effect of GH-RIH on histamine-stimulated secretion was very modest and observed only after stopping the GH-RIH infusion. Thus GH-RIH suppressed acid and pepsin secretion induced by pentagastrin and a meal, and this effect was accompanied by a suppression of serum growth hormone and gastrin levels which may contribute to the inhibition of gastric secretion observed.     

Effect of smoking on gastric acid secretion in patients with duodenal ulcer

The effect of smoking on gastric secretion was studied in 15 consecutive patients with duodenal ulcer--six normosecretors (basal acid output less than or equal to 3 mEq/h), and nine hypersecretors (basal acid output greater than 3 mEq/h). The volume, acid output, acid concentration, and pH of the gastric juice measured before, during and after 1 h of smoking did not show any significant difference in these patients taken as a single group, or when the normosecretors and hypersecretors were analysed as separate groups (P greater than 0.05 for each parameter in each group). The higher acid output before and during smoking in hypersecretors than in normosecretors was due to the higher acid concentration in the gastric juice (P less than 0.01). Study of the pH curves of the gastric juice after acute smoking showed that hypersecretors had a lower pH for a longer duration compared with normosecretors. This could make the hypersecretors with a history of chronic smoking more prone to developing duodenal ulcer.     

The effect of an oral morning dose of nizatidine and ranitidine on gastric acid secretion in duodenal ulcer patients

The aim of this study was to compare the inhibitory effect and duration of action of a new H2-antagonist, nizatidine (150 mg per os), with ranitidine (150 mg per os) in a group of 10 patients with healed duodenal ulcer. The total inhibitory effect on acid output observed under basal conditions (30 min), during pentagastrin stimulation (120 min) and after stimulation (60 min), is overlapping. However, nizatidine showed a more rapid inhibitory activity -80%, and 31% higher than ranitidine with regard to basal acid output and maximum acid output, during the first hour of stimulation. On the other hand, ranitidine has a more prolonged antisecretory action--more than 27% and 54%, respectively, with regard to maximum acid output during the second hour and the period after hormonal stimulation. Also, variations in pepsin and acid output resulted in overlapping. In conclusion, these results, explainable by the pharmacodynamic property of the two drugs, confirmed the excellent inhibitory capacity of nizatidine, and furnish another reason for its use in clinical practice.     

Enzyme activities in the duodenal mucosa in duodenal ulcer patients

The mucosal enzyme activities of 11 marker enzymes from the brush border, basolateral membrane, and lysosomes of 45 patients with an active duodenal ulcer (DU) were determined by analysis of homogenized biopsy specimens obtained from the duodenal bulb and descending duodenum at endoscopy. They were compared with activities measured in 22 controls. In the duodenal bulb lactase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.0005), and monoamine oxidase (p less than 0.0005) were significantly decreased in DU patients. In the descending duodenum all the brush border enzymes except sucrase were significantly decreased when compared with controls. DU patients with inflammation in the biopsy specimens from the duodenal bulb had decreased levels of lactase (p less than 0.05), sucrase (p less than 0.05), neutral-alpha-glucosidase (p less than 0.05), leucyl-beta-naphthylamidase (p less than 0.05), and acid phosphatases (p less than 0.05) when compared with DU patients with normal histology in this region. In the descending duodenum the activities of leucyl-beta-naphthylamidase (p less than 0.05) were decreased in patients with inflammation compared with those without such histologic changes. DU patients who had taken antacids before the investigation had decreased activities of lactase (p less than 0.05) in the descending duodenum when compared with those who had not taken antacids. Activities of lactase (p less than 0.005), sucrase (p less than 0.005), neutral-alpha-glucosidase (p less than 0.05), and acid beta-glucuronidase (p less than 0.0005) in the descending duodenum were significantly lower in smokers than in non-smokers with active DU.     

Rapid gastric emptying in duodenal ulcer patients

Isosmotic liquid peptone meals adjusted to pH 7, 3, and 1.5 were instilled on separate days into the stomachs of 8 duodenal ulcer patients and 7 healthy controls. Using a marker-dilution method, duodenal acid load (DAL) was measured as the amount of unbuffered hydrogen ions delivered to the duodenum per unit time. Gastric emptying was measured as the total volume of gastric contents, including meal plus gastric secretion, passing through the pylorus per unit time (VPP). Mean pentagastrin-stimulated acid output was not significantly different between the two groups. However, after all three test meals, mean DAL was significantly greater in duodenal ulcer than in normal subjects in both hours of the test, and VPP was significantly greater in ulcer than in normal subjects in the first 40 min. In both groups, following peptone meals of pH 7 and 3, the volume of gastric contents delivered through the pylorus decreased as the amount of free hydrogen ions entering the duodenum increased, but a given load of acid was less effective in slowing emptying in duodenal ulcer patients than in controls. These studies indicate that duodenal ulcer patients empty liquid meals more rapidly than do normal subjects, independent of the initial pH of the meals, and that, in addition, acid inhibition of gastric emptying is defective in duodenal ulcer.Dr. Grossman died May 26, 1981.S. K. Lam was a visiting scientist from the Department of Medicine, University of Hong Kong. Queen Mary Hospital, Hong Kong. M.I. Grossman holds a Veterans Administration Senior Medical Investigatorship.These studies were supported by National Institutes of Arthritis, Metabolism and Digestive Diseases grant AM 17328 to the Center for Ulcer Research and Education and by Veterans Administration Research Funds.This work was presented in part in abstract form at the 80th Annual Meeting of the American Gastroenterological Association, New Orleans, Louisiana, May 19–25, 1979.     

Effect of a single dose of antacid on gastric and duodenal bulb pH in duodenal ulcer patients

Gastric and duodenal bulb pH was measured simultaneously with a multiple pH electrode system in 15 duodenal ulcer patients. A single dose of 10 ml antacid was given 120 min after a liquid standard meal, and the pH was measured for another 90 min. The effect of antacid on duodenal pH, expressed as the time pH is kept above 3.0, was on an average 60 min--shorter in patients with a high gastric acid secretion and longer in normosecretors (p less than 0.01). Regression analysis of simultaneously measured gastric and duodenal bulb pH after antacid showed a highly significant linear correlation with a slope of 1.43, which is significantly greater than 1.0 (p less than 0.01), indicating that antacid has a more pronounced effect on duodenal pH than on gastric pH.     

Effect of cimetidine on augmented gastric blood flow in duodenal ulcer patients.

Blood flow in the human stomach was measured during operation with a 85Krypton washout method which made simultaneous determinations of total blood flow and intramural flow distribution possible. The antrum and the corpus of the stomach could be investigated separately. Eleven patients with duodenal ulcer disease were studied during pentagastrin infusion and after the addition of cimetidine, 3 mg/kg bw, to evaluate the effect of the drug on augmented gastric blood flow. Eight recordings were made over the corpus of the stomach and three recordings over the antrum. Cimetidine caused a 66 +/- 5% decrease (mean +/- SE; range 56-86) in acid secretion and a 62 +/- 5% decrease (range 44-91) in the corpus mucosal blood flow within 15 minutes. Changes were only seen in the acid secreting part of the stomach while the antral circulation remained unaltered. It is concluded that the decrease in pentagastrin induced vasodilatation in the stomach seen after giving cimetidine was secondary to an inhibition of acid secretion.     

Histamine and duodenal ulcer: effect of omeprazole on gastric histamine in patients with duodenal ulcer.

Gastric mucosal concentrations of histamine and of its metabolic enzyme, histamine methyltransferase activity, were measured in patients with duodenal ulcer disease and patients with an apparently normal stomach and duodenum. Patients with duodenal ulcer had significantly less (p less than 0.05) mucosal histamine (median 204 nmol/g) than control subjects (median 252 nmol/g). There was no significant difference between the two groups in their histamine methyltransferase activity values. Omeprazole therapy did not significantly change mucosal histamine (+23%), histamine methyltransferase activity (+5%), histamine release before (+5%) or during (+7%) pentagastrin infusion. It significantly decreased acid secretion during pentagastrin stimulation (median -73%, p less than 0.001). Omeprazole, like cimetidine, does not stop histamine release during pentagastrin stimulation.     

A comparison of omeprazole and ranitidine for duodenal ulcer in South African patients

The study was a multicenter double-blind parallel-group comparison of omeprazole, a proton-pump inhibitor, with the H₂-receptor antagonist, ranitidine, in 206 patients with duodenal ulcer. There were 145 men and 62 women of mixed racial origin with an average age of 40 years (range 19–76); 63 of them were white, 7 black, 135 coloured and 1 Asian. Each drug was given for four weeks and ulcer healing rate, symptom relief, and adverse events were recorded and compared between treatment groups. Patients received either 20 mg omeprazole once daily in the morning (N=104) or ranitidine 300 mg once daily at night (N =106). Healing rates were significantly higher in the omeprazole group than in the ranitidine group at both two weeks (80% vs 52%,P<0.001) and four weeks (95% vs 85%,P<0.05), using the per protocol approach, and these results were confirmed using the intention to treat approach. Omeprazole-treated patients reported significantly less daytime epigastric pain (P=0.02) and heartburn (P=0.04) after two weeks than ranitidine-treated patients. By four weeks, there were no significant differences in symptom reporting between groups. Both treatments were well tolerated, and there were no serious adverse events.The study materials and funding were provided by Astra Pharmaceuticals International     

Effect of proximal gastric vagotomy on basal and vagally stimulated gastric bicarbonate secretion in duodenal ulcer patients

Basal gastric bicarbonate secretion and the response to vagal stimulation accomplished by sham feeding were investigated in duodenal ulcer patients before and after proximal gastric vagotomy. Gastric bicarbonate secretion was measured with a computer-based system, which continuously recorded the pH and PCO2 of the gastric perfusate. Preoperatively, basal bicarbonate secretion was 414 +/- 57 mumol/h (mean +/- SEM, n = 9), and the secretory response to vagal stimulation 691 +/- 83 mumol/h (p less than 0.01). About 2 months after proximal gastric vagotomy the basal gastric bicarbonate secretion was 539 +/- 74 mumol/h, and the response to vagal stimulation 693 +/- 72 mumol/h (p less than 0.01). The basal bicarbonate secretion thus increased by 30% after vagotomy (p less than 0.01) but about 1 year later was not significantly different from the basal preoperative value. In the early postoperative period anticholinergics significantly reduced the enhanced basal bicarbonate secretion to a preoperative level. When tested 1 year after the operation anticholinergics did not affect basal bicarbonate secretion but abolished the response to sham feeding. The findings of the study suggest the existence of cholinergic vagal nerve fibres stimulating human gastric bicarbonate secretion and indicate that inhibitory nerve fibres may modulate gastric bicarbonate secretion.     

Effect of duodenal juice on pathogenesis of gastric ulcer

The purpose of the present study was to elucidate the effect of duodenal juice on development of gastric ulcer, in relation to changes of lipid composition and energy metabolism of the gastric mucosa in dogs. For regurgitation of duodenal juice and stagnation of gastric contents in the stomach, the duodenum was constricted below the papilla of Vater, accompanying with pyloroplasty and upper gastro-jejunostomy. Furthermore, to induce ischemia in the gastric mucosa, 0.5 ml of 1% formalin solution was injected into a descending branch of the left gastric artery. Three weeks later, U1 II-III gastric ulcer developed at the formalin injected area with severe gastritis but not with hyperacidity, and the histologic findings were similar to the one of a human gastric ulcer with hypoacidity. On assay of lipid composition in the gastric mucosa, lecithin decreased and both lysolecithin and NEFA increased, showing that lecithin of the gastric mucosa was decomposed by phospholipase A2 of the duodenal juice. In the gastric mucosa, ATP and energy charge decreased, and AMP and lactate increased, indicating that the energy metabolism was led to anaerobic glycolysis. These results revealed that the gastric mucosa becomes very fragile when duodenal juice regurgitates into the stomach and that gastric ulcer may develop even without hyperacidity when the microcirculation is disturbed in this condition.