peptones and Duodenal-Ulcer

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.

Topics: Adult; Double-Blind Method; Duodenal Ulcer; Eating; Gastric Acid; Gastric Acidity Determination; Gastric Emptying; Gastric Juice; Gastrins; Humans; Pepsin A; Peptones; Prostaglandins F, Synthetic; Ranitidine; Stomach; Vasodilator Agents

Mifentidine is a new H2-receptor antagonist with distinct characteristics of potency and long plasma half-life. The aim of this study was to evaluate the effects of mifentidine on peptone meal-stimulated gastric acid secretion. Nine duodenal ulcer patients in remission were enrolled in the study and given in double-blind and at random, on two different occasions, a single tablet of 10 or 20 mg mifentidine or placebo according to an incomplete balanced block design. Ninety min after ingestion of the drug, basal gastric secretion was collected for 30 min and volume, pH and acid output determined. Thereafter, the acid output following peptone meal-stimulation was measured for 2 h by a modified version of the intragastric titration method of Thompson and Swierczek. Plasma samples were collected for gastrin and mifentidine determinations. Basal acid output was strongly inhibited by both the low dose (-78%) and the high dose (-98%) (p less than 0.01). The peptone meal-stimulated acid output was reduced in a dose-dependent manner (-45% by 10 mg and -90% by 20 mg). The drug did not affect the fasting serum gastrin levels but increased, although not significantly, the gastrin response to food. The log of the area under the mifentidine plasma levels correlated linearly with total acid output (p less than 0.01). The results of this study indicate that mifentidine dose-dependently suppresses basal acid secretion and reduces peptone-stimulated gastric acid secretion in duodenal ulcer patients.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Female; Food; Gastric Acid; Gastrins; Humans; Imidazoles; Male; Middle Aged; Peptones; Random Allocation

The effects of pirenzepine and ranitidine alone and combined, on gastric acid secretion and gastrin release stimulated by liquid peptone meal were evaluated in 12 duodenal ulcer patients. Six patients received placebo and ranitidine 150 mg per os and the other six patients were given placebo, pirenzepine 50 mg and pirenzepine 50 mg plus ranitidine 150 mg per os, according to randomized sequences. In the first experiment ranitidine markedly inhibited (69%) gastric acid secretion for entire two hours period (p less than 0.01). In the second experiment acid secretion after pirenzepine, was reduced by 39% while the combination of pirenzepine plus ranitidine almost completely inhibited the meal stimulated acid secretion (99%). Mean integrated gastrin responses after pirenzepine and ranitidine alone as well as pirenzepine plus ranitidine were not significantly different from placebo. The results of these studies show that in duodenal ulcer patients, the simultaneous block of muscarinic and H2-receptors, suppresses meal stimulated gastric acid secretion, without affecting gastrin release. This therapeutic combination might be used in clinical situations (non-responders, Zollinger-Ellison syndrome) in which complete inhibition of gastric acid secretion is needed.

Topics: Adult; Drug Therapy, Combination; Duodenal Ulcer; Female; Food; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptones; Pirenzepine; Random Allocation; Ranitidine

The aim of this study was to compare the effects of atropine with those of placebo and pirenzepine on food-induced gastrin release, and gastric and acid secretion. Three groups of subjects were studied: 8 healthy volunteers; 8 duodenal ulcer patients, and 6 vagotomized patients. Gastric acid secretion and serum gastrin were studied in each subject on 3 different days, after placebo, atropine or pirenzepine, given in random order. In each group, acid secretion was significantly depressed by atropine and pirenzepine. Unlike pirenzepine, atropine induced a significantly increase in serum gastrin in both healthy volunteers and duodenal ulcer patients. None of the treatments caused differences in gastrin response in vagotomized patients.

Topics: Adult; Atropine; Benzodiazepinones; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Kinetics; Male; Middle Aged; Peptones; Pirenzepine; Vagotomy

Combinations of H2-receptor antagonists and classical anticholinergics inhibit stimulated gastric acid secretion more than either drug alone. In double blind, placebo controlled, randomised studies we have compared the effects of single and combined intravenous bolus injections of cimetidine and pirenzepine on peptone-stimulated acid secretion and serum gastrin in man. Combined injection of 3.0 mg/kg cimetidine and 0.3 mg/kg pirenzepine suppressed stimulated acid secretion significantly more than either drug alone, and by 90% in healthy volunteers (n = 8) and patients with duodenal ulcer (n = 5). Side-effects (prolactin stimulation, blurred vision) were diminished by reducing the combined dosages to 1.5 mg/kg cimetidine, to 0.075 and 0.15 mg/kg pirenzepine in another series (n = 10). Postprandial gastrin was not affected by any combination. Combination of cimetidine and pirenzepine suppress food-stimulated gastric secretion more effectively than combination of H2-blockers with classical anticholinergics. Pirenzepine--unlike classical anticholinergics--may distinguish between different subclasses of muscarinic receptors and have a more selective antimuscarinic action. Its interaction with H2-receptor antagonists on parietal cell function seems to be synergistic. Such a combination could be of advantage in patients with gastrinoma, in patients with ulcers and hypersecretion resistant to single drug treatment, and in critically ill patients as prophylaxis of stress ulcer bleeding.

Topics: Adult; Benzodiazepinones; Cimetidine; Drug Interactions; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Guanidines; Humans; Male; Peptones; Piperazines; Pirenzepine; Prolactin

Topics: Clinical Trials as Topic; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Gastrins; Histamine H1 Antagonists; Humans; Imidazoles; Male; Middle Aged; Peptones; Receptors, Drug; Sulfides; Thiourea

S-0509, 2-[(tert-butoxycarbonylmethyl) [(m-(carboxy-phenyl)-ureidomethyl-carbonyl]] aminobenzo phenone, was developed as a potent and selective CCKB/gastrin receptor antagonist that does not affect the central nervous system.. We evaluated the effects of S-0509 on gastric acid secretion and duodenal ulcerogenic and healing responses in rats comparing it with L-365,260, another CCKB/gastrin receptor antagonist.. S-0509 (0.1 approximately 10 mg/kg, i.d.) was able to dose-dependently decrease basal acid secretion and inhibit the acid secretory responses induced by both pentagastrin (60 microg/kg/h, i.v.) and peptone (10%, i.g.) but not histamine (4 mg/kg/hr, i.v.) or carbachol (60 microg/kg/h, i.v.). L-365,260 (10 and 30 mg/kg, i.d.) caused only partial a suppression of the acid secretory response to pentagastrin but not to other stimuli, including peptone treatment. On the other hand, a duodenal ulcerogen, mepirizole (200 mg/kg, s.c. ) caused an increase in acid secretion and resulted in penetrating ulcers in the proximal duodenum, and these ulcers gradually healed over 3 weeks. S-0509 significantly inhibited both the acid secretory (> 1.0 mg/kg, i.d.) and ulcerogenic (> 3 mg/kg, p.o.) responses induced by mepirizole when it was given as a pre-treatment. It also promoted significantly the healing of these ulcers (> 3 x 2 mg/kg, p. o.) when it was given twice daily for 14 days. In contrast, L-365, 260 (30 mg/kg) tended to reduce the severity of mepirizole-induced duodenal ulcers, with a slight inhibition of acid secretion, but it caused no influence on the healing response of these ulcers.. These results confirmed that S-0509 is a selective CCKB/gastrin receptor antagonist with potent antisecretory action in vivo conditions, and further demonstrated that this agent not only prevents the development of duodenal ulcers but also shows healing promoting action on duodenal ulcers, probably through the blockade of CCKB/gastrin receptors.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzodiazepinones; Benzophenones; Dose-Response Relationship, Drug; Duodenal Ulcer; Epirizole; Gastric Acid; Gastric Mucosa; Hydrogen-Ion Concentration; Male; Pentagastrin; Peptones; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin

H. pylori infection is associated with acid-peptic disease, although its role in the pathogenesis is unclear. The purpose of this study was to determine if chronic infection in asymptomatic subjects impairs the inhibition of meal-stimulated gastrin and acid secretion that is observed normally at low intragastric pH. Presence of infection was determined by both C-14 urea breath test and serology. Acid secretion was measured under basal conditions and in response to peptone meal stimulation and pentagastrin. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and during peptone meal stimulation. Intragastric titration with 1% peptone during the first hour, and 8% peptone during the second hour, was performed at both pH 7.0 and 2.5 on different days to compare the inhibition of gastrin and acid secretion. Compared to noninfected subjects, asymptomatic individuals infected with H. pylori had significantly increased: (1) basal gastrin values (P < 0.005); (2) 8% peptone-stimulated gastrin responses at both pH 7.0 and 2.5 (P < 0.05); and (3) 8% peptone-stimulated acid output at pH 2.5 (P = 0.01). During the second hour of peptone-stimulation, subjects infected with H. pylori had significantly decreased inhibition of gastrin (52% vs 95%) (P = 0.002) and acid (30% vs 81%) (P = 0.01) secretion from pH 7.0 to 2.5. Thus, chronic infection with H. pylori results in impaired inhibition of gastrin and acid secretion at low intragastric pH during the second hour of peptone meal stimulation. These defects may be unrelated to the pathogenesis of acid-peptic disease, since they occur in asymptomatic subjects infected with H. pylori.

Topics: Adult; Aged; Duodenal Ulcer; Feedback; Food; Gastric Acid; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Peptones

To examine the role of gastrin as a major mediator of meal-stimulated acid secretion at low and high intragastric pH, gastric acid secretory responses after exogenous and endogenous stimulation were studied in relation to circulating plasma gastrin levels in 19 healthy control subjects and in 18 patients with inactive duodenal ulcer disease. Gastrin was given intravenously in stepwise fourfold-increasing doses from 3.1 to 800 pmol.kg-1.h-1 over consecutive 30-minute periods. Circulating plasma gastrin and acid secretion rates, measured by intragastric titration, were compared with the values obtained during endogenous stimulation by intragastric meals of 0.5, 1, 2, 4, and 8 g% peptone at either pH 5.5 or pH 2.5. The studies showed that circulating gastrin is a major regulator of acid secretion in the presence of peptone in both healthy controls and subjects with duodenal ulcers. Patients with duodenal ulcers had higher acid secretion rates in response to endogenous and exogenous stimulation. In duodenal ulcer subjects and healthy controls, acid secretion in response to higher doses (2-8 g%) of peptone was inhibited at low intragastric pH. This pH inhibition could be fully explained by diminished gastrin release. Patients in the DU group differed from the controls by diminished inhibition of acid secretion at intragastric pH 2.5 when low doses (1 g%) of peptone meals were used. In summary, gastrin is a major regulator of endogenously stimulated acid secretion at high and low intragastric pH in healthy subjects. DU patients differ from healthy controls by higher total acid secretion rates and diminished inhibition of acid secretion when low concentrations of peptone are present in the stomach.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Peptones

A comparison was made between use of isotonic 0.15 M sodium chloride and 5.8 g/100 ml glucose solutions for measurement of gastric acid secretion by intragastric titration in normal and ulcer subjects. Glucose distention did not cause significantly different acid secretion than saline distention in either group. The total amounts of glucose entering the duodenum over the 3.5-hr study period were 99 g in normal subjects and 122 g in ulcer subjects. In normal subjects, circulating gastrin-related acid secretion curves were not significantly different during endogenous peptone and exogenous G-17 stimulation using either the glucose or the saline meals. This finding provides evidence that glucose meals of this size do not alter sensitivity to gastrin. With glucose meals, inhibition of gastric emptying caused retention of a sufficient volume in the stomach to permit accurate continuous intragastric titration. Saline meals caused pronounced diarrhea which was not seen after glucose meals. Glucose distention intragastric titration allows reliable comparisons of endogenously and exogenously stimulated gastric acid secretion without serious side effects and is especially suitable for studying acid secretion in duodenal ulcer subjects.

Topics: Adult; Aged; Duodenal Ulcer; Evaluation Studies as Topic; Food; Gastric Acid; Gastric Acidity Determination; Gastric Emptying; Gastrins; Glucose; Humans; Infusions, Parenteral; Male; Middle Aged; Peptones; Sodium Chloride; Time Factors

In 19 DU-patients and in 15 control subjects acid secretion tests were performed by continuous aspiration or by intragastric titration. Pentagastrin (6 micrograms/kg subcutaneously) or a 20% peptone solution (intragastric instillation) were used for stimulation. In 10 control subjects pentagastrin stimulated acid secretion was within the normal range, hypersecretion (greater than 32 mmol/h) was found in the other 5. 14 DU-patients showed hypersecretion, 5 had normal acid secretion. In contrast to these findings intragastric peptone stimulation caused a very uniform acid secretion within each group. Based on these results ulcer patients and healthy controls could be discriminated more exactly. Acid secretion and serum gastrin concentration were significantly higher in DU patients than in controls. There was a significant correlation between maximal gastrin concentrations and peak acid output after peptone stimulation.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Pentagastrin; Peptones; Solutions

We studied 25 duodenal ulcer patients and 14 age- and sex-matched normal controls to determine whether gastric acid secretion in duodenal ulcer patients is abnormally sensitive to stimulation by gastrin endogenously released in response to meals. Acid response to saline and to 0.5, 1.0, 2.0, 4.0, and 8.0% peptone infused into the stomach was measured by 30 min intragastric titration. Total serum gastrin (G-total) and serum heptadecapeptide gastrin (G17), fasting and 30 min after each test meal, were measured by specific radioimmunoassays. In 19 ulcer patients and 11 normal subjects (controls), acid response to graded doses (11, 33, 100, and 300 pmol kg(-1) h(-1)) of G17-I were also measured. Mean acid output in response to each dose of peptone was significantly higher in duodenal ulcer patients than in the controls. Gastrin levels in ulcer patients and controls were not significantly different. Within individual patients and controls, both G-total and G17 were significantly correlated with meal-stimulated acid output regardless of whether the absolute, basal-corrected, or distention-corrected values for acid output were examined (median r ranged from 0.82 to 0.94, P < 0.001). From the individual regression lines, the gastrin concentrations corresponding to half of the highest observed meal-stimulated acid response (D(50m)) were calculated. Mean D(50m) for G-total and G17 were significantly lower in duodenal ulcer patients than in controls both in the overall group and in pairs of ulcer patients and controls matched on the basis of highest observed meal-stimulated acid responses, or on the basis of maximal acid output in response to synthetic human G17. The dose of exogenously administered G17 required for half maximal G17 acid response mean D(50g), was significantly less in patients than in control subjects. In both ulcer and control subjects, D(50g) correlated significantly with D(50m). This and the significant correlation between meal-stimulated G17 and acid response strongly suggest that the endogenously released gastrin was responsible for most, if not all, of the postpeptone acid output.We conclude that after peptone test meals, gastric acid secretion in duodenal ulcer patients was abnormally sensitive to stimulation by endogenously released gastrin.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Food; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Peptones; Remission, Spontaneous; Time Factors

Fourteen male patients with duodenal ulcer were stimulated by a 10% peptone meal, and acid secretion was measured by continuous intragastric titration. The results were compared to the effects of intravenous infusion of pentagastrin given in a dose of 6.0 microgram/kg-hour on gastric acid secretion in the same 14 patients. Acid secretion reached the peak in the third 15-min period after peptone instillation and it was similar to that peak acid output/15 min produced by infusion of pentagastrin. Acid secretion in response to peptone in the second hour gradually diminished towards the basal level, on the contrary, during i.v. infusions of pentagastrin the acid secretion was well sustained. The acid response to peptone solution or pentagastrin infusion did not differ significantly in the first hour, but in the second hour the difference was significant. It is concluded that the gastric acid secretion induced by peptone is comparable to the effect of the highest dose of pentagastrin infusion only in the first hour. Reproducibility of gastric response to peptone and to pentagastrin infusion was very good (r = 0.79 and 0.87, respectively).

Topics: Adult; Duodenal Ulcer; Gastric Juice; Humans; Infusions, Parenteral; Male; Middle Aged; Pentagastrin; Peptones; Secretory Rate

Topics: Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Peptones; Perfusion; Sodium Chloride; Stimulation, Chemical; Time Factors

The effect of 15(S)-15-methyl PGE2, methyl ester (15-ME-PGE2), used intravenously in a standard dose of 0.5 mug/kg-hr on gastric secretion and serum gastrin level was studied in 6 duodenal ulcer patients. 15-Me-PGE2 caused an immediate and almost complete inhibition of basal gastric acid and pepsin secretion. Acid secretion induced by a peptone meal and determined by intragastric titration technique was almost as high as the maximal response to histamine and accompanied by a significant rise in serum concentration of immunoassayable gastrin. 15-Me-PGE2 caused a sudden and complete inhibition of gastric acid response to a peptone meal. 15-Me-PGE2 did not significantly affect serum gastrin levels both under basal conditions and in response to a peptone meal. Gastric acid and pepsin output induced by maximal stimulation with pentagastrin (4 mug/kg-hr) was inhibited by 15-Me-PGE2 by about 70% and that induced by histamine by about 45%. After the withdrawal of 15-Me-PGE2 infusion, gastric secretion remained reduced for the remainder of the test. We conclude that 15-Me-PGE2 is a very strong inhibitor of gastric acid and pepsin secretion induced by various secretory stimuli, particularly under basal conditions and in response to a meal. In view of prolonged inhibitory activity, 15-Me-PGE2 may have clinical potential in the treatment of peptic ulcer disease.

Topics: Adult; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Male; Pentagastrin; Peptones; Prostaglandins E

Serum gastrin and gastric acid responses to a test meal of 10% peptone were measured in six duodenal ulcer patients using intragastric titration at pH levels ranging from 5.5 to 1.0. In this way the pH profile for inhibition of serum gastrin release and gastric acid secretion was established. A peptone meal adjusted to pH 5.5 produced gastric acid similar to the maximal response to histamine. A graded decrease of pH of the peptone meal to 1.0 resulted in the progressive inhibition of the gastric acid secretion and the concomitant suppression of the serum gastrin level. Exogenous secretin given in graded doses ranging from 0.25 to 2.0 U/kg-hr caused a dose-related inhibition of gastric acid secretion and the suppression of serum gastrin level. The results of the study indicate that gastric acid secretion and the rise in serum gastrin levels in response to an experimental meal are less when the gastric contents become more acid. The mechanism may involve release of secretin from the small intestine by acid.

Topics: Adult; Depression, Chemical; Duodenal Ulcer; Food; Gastric Juice; Gastrins; Histamine; Humans; Hydrogen-Ion Concentration; Infusions, Parenteral; Peptones; Radioimmunoassay; Secretin; Secretory Rate

Topics: Adult; Depression, Chemical; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Histamine; Humans; Imidazoles; Infusions, Parenteral; Insulin; Intubation, Gastrointestinal; Pentagastrin; Pepsin A; Peptones; Secretory Rate; Sulfides; Thiourea

The action of intravenous atropine on meal-and pentagastrin-induced gastric acid secretion was studied in six duodenal ulcer patients.A test meal of 10% peptone solution adjusted to pH 5.0 was maintained in the stomach at at distention presure of 15 cm H(2)O, and a modification of the intragastric titration method of Fordtran and Walsh was used to measure gastric acid output by monitoring the rate at which a solution of 0.5 M sodium bicarbonate had to be added to keep the pH of the gastric content constant at the initial (pH 5.0) value. Serum gastrin concentrations were measured simultaneously by radioimmunoassy. The dose of 25 mug/kg-h atropine inhibited meal-induced acid secretion by about 70% and that evoked by pentagastrin by about 30%. The serum gastrin response to the test meal was not significantly altered by atropine. We conclude that atropine is a very strong inhibitor of meal-induced gastric acid secretion and does not significantly change serum gastrin response to feeding in duodenal ulcer patients when postprandial gastric acidity (pH 5.0) and intragastric pressure (15 cm H(2)O) are kept constant.

Topics: Adult; Atropine; Duodenal Ulcer; Eating; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Middle Aged; Pentagastrin; Peptones; Pressure; Radioimmunoassay; Stomach

Topics: Ammonia; Biomedical Research; Blood; Duodenal Ulcer; Gastric Acid; Gastric Juice; Geriatrics; Histamine; Liver Cirrhosis; Peptones; Pharmacology; Potassium; Sodium