tetragastrin and Stomach-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

Gastric blood circulation maintains the structure and functions of the stomach, and thereby is closely associated with the pathogenesis and the healing of gastrointestinal lesions. Gastric mucosal blood flow, regulated by systemic neural and humoral factors, is also modified by local metabolic factors such as prostaglandins, leukotrienes. PAF and other endogenous chemical mediators in mucosa. Endothelium-derived factors that are produced by vascular endothelial cells, inducing relaxation or contraction of the blood vessels, are also recognized as basic mediators that regulate the circulation in the stomach.. The regionally disturbed gastric circulation in combination with the presence of acid is closely associated with the pathogenesis of NSAIDs and ethanol-induced gastric lesions. Blood flow and oxygenation in the surface mucosa surrounding the peptic ulcer change during healing, depending on the quality of the ulcer healing process: an increased blood circulation with increased oxygen supply to the ulcer margin is important for rapid ulcer healing shown by reflectance spectrophotometry. Factors altering the blood flow during the ulcer healing are discussed.

Topics: Animals; Blood Flow Velocity; Carbachol; Dogs; Ethanol; Gastric Acid; Gastric Mucosa; Hemoglobins; Histamine; Humans; Indomethacin; Laser-Doppler Flowmetry; Male; Microcirculation; Middle Aged; Rats; Rats, Sprague-Dawley; Regional Blood Flow; 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

The effects of tetragastrin on mucus glycoprotein (mucin) metabolism and mucosal protection in rat gastric mucosa were investigated. Rats were administered with various doses of tetragastrin (12, 120, or 400 micrograms/kg body weight; s.c.), followed by 50% ethanol-induced gastric injury. Tetragastrin caused a significant increase in mucin content in the corpus mucosa and prevented 50% ethanol-induced gastric mucosal damage in a dose-dependent manner. For assessment of the effects of tetragastrin on the metabolism of gastric mucin in detail, changes in mucin distribution in the three different layers of rat gastric mucosa were examined one hour after single administration of tetragastrin. A significant increase in the mucin content was noted in the mucus gel and surface mucosal layer. Mucin content in the deep mucosa corresponding mainly to the mucus neck cell mucin underwent virtually no change by this treatment. An increase in mucin in the mucus gel and surface mucosa would thus appear due to the administration of tetragastrin and may possibly be related to the protective action of the gastric mucosa against injury. The data demonstrate a possibility that gastrin may have potential for enhancing gastric mucosal protection associated with mucus secretion and/or mucus synthesis on the surface mucosa of rat gastric mucosa.

Topics: Animals; Dose-Response Relationship, Drug; Ethanol; Gastric Mucins; Gastric Mucosa; Hydrogen-Ion Concentration; Injections, Subcutaneous; Male; Peptic Ulcer Hemorrhage; Rats; Rats, Wistar; Stomach Ulcer; Tetragastrin

The protective effect of the secretory state of gastric mucosa against acute gastric mucosal injury due to hemorrhagic shock was investigated in rats with tetragastrin infusion. A total of 26 male Spraque-Dawley rats were divided into 3 groups (n = 6, 8, and 12, respectively). Tetragastrin (8 micrograms/Kg/h) was added into the normal saline infusion (5 ml/h) in group 3, but not in the other 2 groups. The mucosal surface was instilled with 0.1 N HCl (pH = 1) in group 2, with normal saline (pH = 7) in group 1, and with nothing in group 3. Hemorrhagic shock at 40 mmHg of arterial pressure was induced by withdrawing blood from the femoral artery, and was maintained at this level for 20 minutes; later, the shed blood was re-infused. During hemorrhagic shock, scattered areas of white circumscribed white lesions appeared on the mucosal folds of the glandular region in all of group 2 and in 8 (with gastric pH less than 3) of group 3, yet did not appear in group 1 or in the remaining 4 (with gastric pH greater than 3) of group 3. After reinfusion, varying degrees of mucosal hemorrhage from the whitened areas occurred in all of group 2 and in 8 (with pH less than 3) of group 3, but in only one of group 1. The severity of acute gastric mucosal injury in group 2 and group 3 (n = 8, with gastric pH less than 3) was significantly greater than group 1. However, it was not significantly different between groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Gastric Acidity Determination; Gastric Mucosa; Male; Rats; Rats, Inbred Strains; Shock, Hemorrhagic; Stomach Ulcer; Tetragastrin

In our previous reports, low dose acid secretagogues caused increase in corpus mucus glycoprotein content in rats. This increase was not due to the direct action of protons. The present study was conducted to determine whether this increase has a mucosal function or not Rats were given histamine (0.8 mg/kg) intraperitoneally or tetragastrin (12 micrograms/kg) subcutaneously. One hour following the acid secretagogues administration, the animals were given 1 ml of 30, 40 or 50% ethanol orally and then sacrificed after one hour. Gastric mucus glycoproteins were isolated from the corpus region of stomach. The following results were obtained: 1) Histamine prevented the gastric mucosal damage and the decrease of corpus mucus glycoprotein content induced by 40% ethanol ingestion. 2) Tetragastrin prevented the gastric mucosal damage induced by 30 approximately 50% ethanol ingestion and the decrease of corpus mucus glycoprotein content induced by 40 approximately 50% ethanol ingestion. Based on these results, the increase of corpus mucus glycoprotein content induced by acid secretagogues has a mucosal function. Moreover, tetragastrin strengthened the mucosal defence together with acid secretion.

Topics: Animals; Ethanol; Gastric Acid; Gastric Mucosa; Gastrins; Glycoproteins; Histamine; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Tetragastrin

Topics: Adult; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Pepsin A; Recurrence; Stomach Ulcer; Tetragastrin

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

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

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

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

Topics: Animals; Anti-Ulcer Agents; Benzodiazepinones; Carbachol; Drug Interactions; Electric Stimulation; Gastric Juice; Gastrointestinal Motility; Male; Meat; Piperazines; Rats; Stomach Ulcer; Tetragastrin; Time Factors; Tissue Extracts; Vagus Nerve

Clinically, most gastric ulcers are located in the region of the incisura angularis, but they are least found along the greater curvature. To elucidate this difference, following experiments were carried out. A total of 22 mongrel dogs were used. A set of bipolar electrodes and/or a water-proof strain gage were chronically implanted at both the incisura and the corresponding site of the greater curvature. Electrical and contractile activities of these two sites were compared at the fasted state and under the stimulations by food, neostigmine and tetragastrin. Results are summarized as follows. 1. Electromyographically, the propagation velocity was always greater along the greater curvature than the lesser curvature. The discharge interval of BER and incidence of antiperistalsis were identical for both the lesser and greater curvature. 2. Through the course before and after the stimulation, there was no difference in the frequency of contraction waves, while the amplitude and motility index of the contraction were definitely greater at the incisura than the corresponding greater curvature. In conclusion, the present study revealed that the contractile force of the incisura was always greater than that of the corresponding greater curvature. It is possible that the peristaltic contraction could cause stronger repetitive ischemic condition of the incisura than the corresponding greater curvature. It is estimated that the gastric motility is one of the important factors for the predilection or delayed healing of gastric ulcers seen in the region of the incisura angularis.

Topics: Action Potentials; Animals; Dogs; Electromyography; Gastrointestinal Motility; Neostigmine; Stomach Ulcer; Tetragastrin