tetragastrin and Duodenal-Ulcer

It remains controversial whether or not Helicobacter pylori infection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed.. To investigate by EGT the effects of H pylori eradication on the state of gastric acid secretion in patients with peptic ulcer.. Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whom H pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication.. In patients with duodenal ulcer, the mean EGT value before H pylori eradication was higher than that in H pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer before H pylori eradication was lower than that in H pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value.. The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.

Topics: Adult; Aged; Atrophy; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Stomach Ulcer; Tetragastrin

We investigated the effects of the newly synthesized proton pump inhibitor TY-11345, (+/-)-2-[(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin- 9-yl)sulfinyl]-1H-benzimidazole sodium salt, on gastric mucosal proton pump (H+/K(+)-ATPase) activity, gastric acid secretion and gastro-duodenal lesions in experimental animals. TY-11345 potently inhibited H+/K(+)-ATPase activity in isolated rabbit gastric mucosal microsomes; and the inhibitory effect was enhanced under weak acid conditions, the IC50 (concentrations that inhibit the enzyme activity by 50%) being 5.8 microM and 9.9 microM at pH 6.0 and pH 7.4, respectively. In Ghosh & Schild rats, intravenous injection of TY-11345 significantly inhibited gastric acid secretion stimulated by tetragastrin; the effect of TY-11345 was twice as potent as that of omeprazole. In pylorus ligated rats, TY-11345 inhibited basal gastric acid secretion by both the intraduodenal and oral routes, with ED50 values of 1.2 and 4.0 mg/kg, respectively. These effects were 9 and 5 times more potent than those of omeprazole, respectively. Moreover, the antisecretory effect of TY-11345 persisted for more than 24 hr in pylorus ligated rats. In experimental ulcer models, TY-11345 prevented the formation of water-immersion stress, ethanol or indomethacin-induced gastric lesions and mepirizole-induced duodenal lesions in rats. The antiulcer effects of TY-11345 were 3 to 15 times more potent than those of omeprazole. These results suggest that TY-11345 has potent antisecretory and antiulcer effects which are exerted by suppression of H+/K(+)-ATPase activity in gastric parietal cells, so that TY-11345 should be useful for the clinical treatment of peptic ulcer diseases.

Topics: Acetates; Acetic Acid; Animals; Anti-Ulcer Agents; Benzimidazoles; Duodenal Ulcer; Epirizole; Ethanol; Gastric Mucosa; Immersion; In Vitro Techniques; Indomethacin; Male; Microsomes; Omeprazole; Proton Pump Inhibitors; Rabbits; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Stress, Psychological; Tetragastrin

Somatostatin in gastric juice was determined in normal subjects and patients with duodenal ulcer. Gel exclusion chromatography of gastric juice revealed that the main immunoreactivity existed at the position of somatostatin-14. A large amount of somatostatin was present in gastric juice, and the quantity increased following tetragastrin stimulation. Furthermore, there was a good inverse correlation between somatostatin concentration and acidity of gastric juice; however, there was no difference between normal subjects and patients with duodenal ulcer in the amount of somatostatin released into gastric juice.

Topics: Adult; Chromatography, Gel; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastric Juice; Humans; Male; Radioimmunoassay; Somatostatin; Tetragastrin

Patients with duodenal ulcer were classified into responders to H2-receptor antagonist and non-responders in whom duodenal ulcer did not heal within three months with the antagonist. In these patients and healthy controls, modified sham-feeding (MSF) test was performed to elucidate the pathophysiological differences between these groups, especially vagal activity of acid output. After tetragastrin 4 micrograms/kg/hr infusion for one hour, MSF was superimposed to the infusion (G + MSF). The acid output of non-responders (8 cases) and controls (8 cases) significantly increased in G + MSF. On the other hand, the acid output of responders (6 cases) significantly decreased. The acid output of non-responders in G + MSF was also significantly higher than that of controls. The results suggest that vagal activity of non-responders is higher than responders, and that there is disturbance of inhibitory mechanism in vagal system.

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Tetragastrin; Vagus Nerve

Antral G and D cells were microscopically counted by the immunoperoxidase method in the resected stomachs of 18 patients with duodenal ulcer (DU group), 4 with recurrent duodenal ulcer after selective proximal vagotomy (SPV-REC group) and 6 with early gastric cancer in the corpus (control group). In DU and SPV-REC groups, preoperative acid secretion stimulated by the tetragastrin (Tg-MAO, Tg-PAO) was examined. In 9 patients of DU and SPV-REC groups, adrenalin stimulated acid secretion (Adr-PAO) and integrated gastrin response (Adr-PGO) were also examined. The G cell count in DU group (Tg-MAO greater than or equal to 20) and SPV-REC group were significantly more than in DU group (Tg-MAO less than 20) and control group. In DU and SPV-REC groups, a significant correlation was observed between Tg-PAO and total G cell count. In 9 DU patients, a significant correlation was observed between the total G cell count and Adr-PGO or Adr-PAO, between Adr-PGO and Adr-PAO or Tg-PAO and between Tg-PAO and Adr-PAO. The above results suggested that increase of antral G cell counts is one of the great cause of duodenal ulcer and recurrent ulcer after SPV, greatly affecting on increase of acid secretion intermediating serum gastrin. Both Tg-PAO and Adr-PAO were regarded as good index of functional G cell mass of the antrum.

Topics: Adolescent; Adult; Aged; Cell Count; Duodenal Ulcer; Epinephrine; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pyloric Antrum; Recurrence; Tetragastrin; Vagotomy, Proximal Gastric

To clarify the contributive factors in the recurrence of duodenal ulcer, the present study was carried out on 65 male patients with active duodenal ulcers and 20 healthy male subjects. After having verified that the ulcer had healed, gastric acid secretory responses to graded doses of tetragastrin from 62.5 to 16,000 ng/kg/hr were investigated using a logarithmic transformation model. Several clinical features were also investigated. The patients were divided into three groups based on the later endoscopic follow-up study for two years. The early-recurrent group included 16 patients with recurrence occurring within three months. The late-recurrent group included 25 with recurrence occurring after three months. The nonrecurrent group included 24 patients without recurrences during the follow-up period. The 20 healthy male subjects were defined as a control group. The results were as follows: (1) Significant differences were not discerned either in basal and peak acid outputs between the three patients groups. (2) The ED50 value for tetragastrin was lower in the early-recurrent group than in the other three groups. (3) The early-recurrent group showed a higher percentage of smokers than the other patient groups. These results suggest that smoking and increased parietal cell responsiveness correlates strongly with duodenal ulcer recurrence.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Parietal Cells, Gastric; Recurrence; Smoking; Tetragastrin; Time Factors

We defined duodenal ulcers (DUs) not healed within 3 months with H2-antagonists as "intractable", because the recurrence rate of these DUs is higher than that of DUs healed within the same periods, and etiological differences are suggested to exist among these two groups. To verify the pathophysiological differences, gastric analysis including modified sham-feeding (MSF) were performed in 12 intractable, 10 tractable DUs and 5 healthy controls. By MSF stimulation, acid output increased in all subjects and the mean acid output of MSF amounted to about 60% of the tetragastrin maximum. Mean acid output of intractable DU cases was significantly higher than the controls in any stimulatory state and was different only in MSF with tractable DU. No significant changes of serum gastrin were recognized during MSF and both serum pepsinogen I and II are higher in DU cases than the control in basal state, but the two DU groups show no significant difference or increase by MSF or gastrin stimulation. These data suggest that vagal activity of intractable DUs is higher than not only healthy subjects, but tractable DUs and participation of gastrin in the increase of acid output by MSF might be denied.

Topics: Adult; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Middle Aged; Pepsinogens; Tetragastrin; Vagus Nerve

The results of the initial clinical pharmacology studies of famotidine, a new H2 receptor antagonist, are summarized. These studies indicate that: single oral doses of famotidine (5-80 mg) were well tolerated; famotidine effectively suppressed basal, nocturnal, pentagastrin- and meal-stimulated acid secretion; the duration of the antisecretory action of famotidine was dose related: up to 12 h for the 20-mg dosages, and 18-24 h for the 80-mg dose; the elimination half-life was 3.8 h; 5 mg of famotidine gave acid suppression similar to that of 300 mg of cimetidine; a dose response was identified: 2 h after oral dosing, 5 mg famotidine suppressed stimulated acid secretion to 60% of control and was comparable to 300 mg cimetidine (55% suppression), whereas higher doses of famotidine yielded significantly more suppression of acid secretion (10 mg yielding 70% and 20 mg 90%), significantly greater than 300 mg cimetidine; plasma famotidine concentration and urinary recovery were dose related, and famotidine (10-40 mg) had no effect on serum prolactin. Thus, famotidine is a safe and potent H2 blocker of acid secretion with a long duration of action.

Topics: Animals; Cimetidine; Circadian Rhythm; Dogs; Dose-Response Relationship, Drug; Duodenal Ulcer; Famotidine; Food; Gastric Acid; Half-Life; Histamine; Histamine H2 Antagonists; Humans; Kinetics; Pentagastrin; Pepsin A; Prolactin; Rats; Tetragastrin; Thiazoles; Time Factors

To clarify the protein metabolism in peptic ulcer disease, the amino acid content was determined in gastric juice of gastric ulcer patients (n = 30), duodenal ulcer patients (n = 16), gastroduodenal ulcer patients (n = 8), and hospital controls (n = 8). The amino acid output in the gastric ulcer group was greater than that of the hospital control both in basal and maximal secretion. In the duodenal ulcer group of patients who were high secretors of gastric juice, the amino acid concentration was low, so the amino acid output was also lower than that of the hospital control group. Tetragastrin did not increase the amino acid output in the gastric juice. The amino acid amount may be decided also by the architecture of the gastric mucosa and not only by the ulcer lesion itself. The protein loss from gastric mucosa may well result in hypoproteinemia in peptic ulcer disease of the stomach.

Topics: Adult; Amino Acids; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Humans; Male; Middle Aged; Peptic Ulcer; Stomach Ulcer; Tetragastrin

Topics: Adult; Duodenal Ulcer; Female; Follow-Up Studies; Humans; Male; Middle Aged; Parietal Cells, Gastric; Recurrence; Tetragastrin

The amino acids in human gastric juice were measured in the hospital control (n = 9), gastric ulcer (n = 10), duodenal ulcer (n = 12), gastroduodenal ulcer (n = 9), and gastric cancer patients (n = 16) by high performance liquid chromatography, and the total of 15 kinds of amino acids was correlated with value determined by Ninhydrin method. The patients with gastric cancer had elevated levels of all amino acids, especially alanine, leucine, valine and threonine. In all but the gastric cancer disease groups, the aromatic amino acids, phenylalanine and tyrosine as well as leucine were at high levels in 15 amino acids. The different patterns of amino acids in these four groups tended to correlate with the variabilities of protein loss from the gastric wall.

Topics: Adolescent; Adult; Aged; Amino Acids; Chromatography, High Pressure Liquid; Duodenal Ulcer; Female; Gastric Juice; Humans; Male; Middle Aged; Peptic Ulcer; Stimulation, Chemical; Stomach Diseases; Stomach Ulcer; Tetragastrin

Topics: Adult; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastric Juice; Humans; Male; Middle Aged; Pepsin A; Recurrence; Tetragastrin

In order to explore secretory mechanisms in peptic ulcer, the plasma secretin response to an intraduodenal load of gastric acid stimulated with tetragastrin was studied in 10 patients with duodenal ulcer, nine with gastric ulcer, and five young healthy volunteers. After the injection of tetragastrin plasma secretin level was significantly increased in all subjects. The integrated incremental secretin output significantly correlated with the incremental acid output in the duodenal ulcer group as well as the gastric ulcer group. THere was no significant difference in the integrated incremental secretin output among the three groups. However, the integrated incremental secretin output per unit amount of gastric acid loaded in the duodenum was significantly lower in the duodenal ulcer group than in the other two groups. These results suggest that in patients with duodenal ulcer the secretin release in response to an intraduodenal load of endogenous acid is impaired.

Topics: Adult; Duodenal Ulcer; Duodenum; Female; Gastric Acid; Gastrins; Humans; Hydrochloric Acid; Male; Middle Aged; Peptic Ulcer; Secretin; Stomach Ulcer; Tetragastrin; Time Factors

Praomys (Mastomys) natalensis, an African rodent ranging in size between a mouse and a rat, is more susceptible to the induction of duodenal ulcers by constant infusion of exogenous histamine through an osmotic minipump implanted subcutaneously than other rodent species tested such as mouse, rat, or guinea-pig. By increasing the doses of infused histamine, there were increases in the incidence, intensity, and perforation rate of duodenal ulcers in Mastomys. The induction of duodenal ulcers in Mastomys by tetra- and pentagastrins was unsuccessful, probably because of the limited releasing capacity of the present minipump for use of these two peptides which were sparingly soluble in water. More soluble human synthetic gastrin I was approximately three to four times as potent as histamine for inducing duodenal ulcers in Mastomys. The susceptibility of Mastomys to the induction of duodenal ulcer by cysteamine appears to be comparable to that of rat. The complete suppression of histamine-induced duodenal ulcers of Mastomys was possible by repeated subcutaneous injections of cimetidine.

Topics: Animals; Cimetidine; Cysteamine; Disease Models, Animal; Duodenal Ulcer; Female; Gastrins; Guinea Pigs; Histamine; Male; Mice; Mice, Inbred DBA; Pentagastrin; Rats; Rodentia; Species Specificity; Tetragastrin

Topics: Adolescent; Adult; Age Factors; Child; Duodenal Ulcer; Gastric Juice; Humans; Middle Aged; Pepsin A; Stomach Ulcer; Tetragastrin

Dose-response studies to tetragastrin were performed in patients with duodenal ulcer before and after highly selective vagotomy, hemigastrectomy and truncal vagotomy plus antrectomy. The calculated maximal response and the dose necessary to elicit 50 percent of that response (D50) were calculated by linear transformation of the results. Both highly selective vagotomy and hemigastrectomy were followed by a significant decrease in the stimulated acid output, characterized by a decrease in the calculated maximal response, but no change in the sensitivity of the parietal cells (D50) was observed. This indicates a noncompetitive reduction in the acid output. The calculated maximal response could not be restored to preoperative values by increasing the dose of stimulant. Truncal vagotomy plus antrectomy was followed by severe alteration in gastric physiology, and no linear transformation of the acid output could be made. This investigation shows that maximal acid output was obtained by the same dose of stimulant before and after all three operations studied. Therefore it is not necessary to increase the dose in postvagotomy acid studies.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Pyloric Antrum; Random Allocation; Tetragastrin; Vagotomy

Topics: Aged; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Humans; Male; Middle Aged; Pepsin A; Tetragastrin