[Effect of prolonged pirenzepin administration on the gastric cell populations in the rat (author's transl)].
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Biomedical subjects
Publications and source records attributed to T Lehy.
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Rectosigmoid- or colonoscopy biopsies were performed at different levels of the large intestine of 16 adult subjects free from major intestinal disease. Tissue specimens were subsequently examined by electron microscopy. Four different endocrine cell types could be distinguished on the basis of the shape and ultrastructural appearance of secretory granules, of their silver affinity, and of their morphometry. Type I cells (enterochromaffin cells, 60.5%) were argentaffin and presented granules with widely different morphologies, which could correspond to several subtypes. The three other cell types were nonargentaffin. Type II (21.3%) contained granules with a diameter distribution peak of 200 to 300 nm. Type III cells, rare (3.2%), were characterized by small and infrequent granules with a diameter distribution peak of 150 to 200 nm. Type IV cells (7.4%) were characterized by large and round granules with a diameter distribution peak of 300 to 400 nm and resembled the "L cell" of the small intestine. The most endocrine cell-rich portion of the colon was the rectum (179 of 618 cells examined). Type I cells represented approximately 73% of the endocrine cell population from the cecum to the descending colon and decreased to 42% in the rectum. Both the absolute number and the percentage of type II cells increased from the cecum (8%) to the rectum (31%). Type IV cells also increased in the rectum both in absolute number and percentage (14%). The absolute number of type III cells was too small to enable significant differences to be observed.
Small pieces of pancreatic tissue were obtained at surgery from a subtotal pancreatectomy performed in a 45-day-old child suffering from intractable neonatal hyperinsulinic hypoglycemia. Histological examination was performed using aldehyde fuchsin, Grimelius', and Hellerström-Hellman's stainings, and immunoperoxidase labeling of insulin and gastrin. The pancreatic tissue before explantation showed numerous and sometimes hyperplastic islets, together with isolated insulin-, glucagon-, and gastrin-containing cells scattered among the exocrine tissue, in aspects similar to "B cell nesidioblastosis." These features could be interpreted as an acinoinsular transformation and/or an embryonic malformation. Extralobular endocrine islet formation by budding from ductular structures was evoked, suggesting the persistency of embryonic properties. The pieces were cultivated on rooster plasma coagulum covered with culture medium. In vitro, endocrine cells survived for 43 days, with outgrowth from the explant and with retention of their secretory abilities. After each medium renewal, radioimmunoassays were performed on the culture medium; they showed that insulin and glucagon secretions decreased with time. On the contrary, secretion of immunoreactive gastrin progressively increased, and kept up to 43 days, with subcultures. Some explants developed in a peculiar way, outgrowing as epithelial layers rich in gastrin-secreting cells as indicated by radioimmunoassays performed after they were reexplanted.
The proliferation of antral gastrin cells has been studied in adult mice by combining their immunoperoxidase identification on semithin Epon sections with radioautography after single or multiple injections of [3H]thymidine. After a single injection, nuclear uptake of [3H]thymidine was observed in 0.25% of the well-differentiated gastrin cells. Ten days after six successive injections of the precursor, the labeling index reached 4.5%. This indicated that the renewal of the gastrin cell population was very slow. The turnover time was roughly estimated at 2 to 4 months. Analysis of the labeling index curves obtained during and after the administration of [3H]thymidine confirmed that the majority of the gastrin cells were renewed through replication of other gastrin cells. However, differentiation of a fraction of this gastrin cell population from "other" cells in the antrum could not be excluded.
The combined use of immunocytochemical labelling of gastrin cells and of autoradiographic labelling after a single injection of tritiated thymidine, showed that these endocrine cells are renewed in the antrum of adult mice.
Rats surgically prepared with the antrum transposed onto the colon were compared with suitable control rats, to investigate whether chronic antral stimulation modifies gastrin cell and other endocrine cell populations. Gastrin cell and argyrophil cell density per unit area were studied in antrum using a quantitative method after staining by immunofluorescence and Grimelius argyrophily, respectively. Both gastrin cells and argyrophil cells increased significantly in density per unit area after antrocolic transposition (P smaller than 0.001). The augmentation of gastrin cells per glandular tube (78%) was also significant (P smaller than 0.001). Electron-microscopic observations confirmed these results. On the other hand, in each group, the topographic distribution of the two categories of cells was different, and the number of gastrin cells was statistically greater than that of the argyrophil cells. Thus, it appeared evident that gastrin cells were not argyrophilic. Several hypotheses to explain the mechanism of this hyperplasia of endocrine cells are discussed. It is concluded that the increase in the gastrin cell density could be one possible explanation for the hypergastrinemia observed in the antrocolic transposition model.
Gastrin was given to mice subcutaneously at 8-hr intervals for 20 days. Control animals received only saline injections. With use of [3H]thymidine and radioautography, a significant increase in the production of new parietal cells (P less than 0.01) was observed in the gastrin-treated group. Increases in fundic progenitor cell DNA synthesis and shortened maturation time of the latter were demonstrated. Both could explain the observed changes in parietal cell kinetics. The quantitative estimation of parietal cell population after the administration of gastrin showed an increase in average parietal cell count per unit (P less than 0.01) and in total parietal cell number (P less than 0.05). This was consistent with the observed acceleration in the rate of parietal cell production under influence of gastrin. In contrast, no radioautographic difference in the proliferative activity of the peptic cells was observed between the gastrin-treated and the control mice. Moreover, at the end of the experiment, no changes in average peptic cell count per unit area, or in total peptic cell number, occurred under the effect of gastrin. The observation that peptic cells are renewed in a different way, independently from fundic progenitor cells and from parietal cells, was consistent with their peculiar lack in proliferative response to the hormone.
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Omeprazole efficacy and tolerance were evaluated in 20 patients with longstanding Zollinger-Ellison syndrome (ZES) committed to long-term antisecretory therapy. The study included 13 men and 7 women, aged 53 (30-74) years (median and range). Nineteen patients presented with epigastric pain, 14 with vomiting, and 9 with diarrhea. All patients had gastroduodenal ulcerations, associated with esophagitis in 9 cases. Median and extreme values for basal acid output (BAO) and serum gastrin (SG) levels before omeprazole treatment were 41 (3.7-80) mmol H+/h and 413 (111-11,490) pg/ml, respectively. In 18 patients, omeprazole treatment was initiated because of resistance to H2-antagonists, and in 2 patients because of carbothioamide RP 40749 discontinuation. Initial doses of omeprazole were 60 mg per day in 10 patients and ranged from 80 to 160 mg per day in the others. Esophagogastrectomy was performed in one patient at day 15 because of esophageal stenosis. In the remaining 19 patients, median duration of treatment was 16 (7-54) months and median doses of omeprazole were 70 (20-160) mg per day during the survey. Omeprazole therapy was highly effective in inducing rapid disappearance of clinical abnormalities in 18 of 19 patients. Twenty-two days after initiation of treatment, median BAO was 4 (0-14) mmol/h and ulcerations had healed in 17 of 19 patients. Median BAO was less than 5 mmol/h during follow-up. However, asymptomatic ulcer recurrence was noted in 4 patients, but disappeared quickly after omeprazole doses were increased. Median basal gastrin level was 700 (116-36.625) pg/ml at the least determination and was statistically higher than pretreatment values (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)