misoprostol and Hyperplasia

Dogs were given a prostaglandin analogue, misoprostol, at a dose that significantly increases gastrointestinal epithelial cell proliferation. Both basal and postprandial concentrations of gastrin were significantly higher in the misoprostol-treated dogs and more than doubled after the meal in both the controls and in the test group. Plasma enteroglucagon, cholecystokinin, insulin and glucose-dependent insulinotrophic peptide all increased postprandially, with no effect of misoprostol. Tissue concentrations of bombesin, gastrin and somatostatin were unaffected by misoprostol, but the fundic glucagon-like immunoreactivity was significantly increased. Thus high doses of misoprostol have only minor effects on gastrointestinal regulatory peptides, suggesting that the trophic effect of prostaglandins on the intestinal tract may be direct.

Topics: Animals; Cell Division; Dogs; Gastric Mucosa; Gastrointestinal Hormones; Hyperplasia; Intestinal Mucosa; Male; Misoprostol

Increased mucosal mass is associated with prostaglandin administration, raising the question as to whether this is the consequence of increased cell production or decreased cell loss. 3H-thymidine was injected into 30 test dogs given 300 micrograms/kg/day of the prostaglandin E1 analogue, misoprostol, orally for 11 weeks, and into 30 dogs which had been given the vehicle alone. Six test and 6 control dogs were killed 1 h after thymidine labelling, and the remainder were killed subsequently at timed intervals to determine cell migration rates and transit times. Misoprostol significantly increased the stomach weight, but nonetheless did not significantly increase the labelling index, nevertheless, the number of labelled cells per gland was significantly increased, which was a consequence of the increased gland length. When the data was expressed as a gland cell production rate significant increases were thus observed. The migration rate of cells toward the gastric lumen increased one and a half times in the misoprostol-treated group; however, as the gland length also significantly increased, there was no significant difference in the transit time. It must be concluded that the hyperplasia associated with exogenous prostaglandins is the consequence of increased cell production, not decreased cell loss, and that previous reports to the contrary are the result of failure to allow for concomitant changes in the denominator of proliferative indices.

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Autoradiography; Cell Division; Cell Movement; Dogs; Gastric Mucosa; Hyperplasia; Misoprostol; Organ Size; Stimulation, Chemical

The effects of misoprostol on human gastric antral mucosa were investigated in patients with established diagnoses of either gastric or duodenal ulcer. All patients had pretreatment biopsy. After starting treatment with misoprostol, antral biopsies were taken at four and eight weeks and were fixed in formaldehyde. Following fixation and routine tissue processing, the slides were stained with hematoxylin and eosin. A pathologist from the laboratory preparing the slides reviewed the slides and prepared surgical pathology reports. An identical slide of each biopsy was sent to pathologists at G.D. Searle and Company who were unaware of the diagnoses and who issued an independent descriptive report. Representative cases are presented for discussion. Misoprostol was administered at doses of 100 or 200 micrograms for four or eight weeks. No cellular or mucosal changes were observed. Both groups of pathologists were unable to recognize any dose-related or structural alterations. No special studies were performed on these tissues due to their fixation and sample size. Infiltration of the mucosa by chronic inflammatory cells with a variable number of granulocytes was the most common finding. There were a few cases of goblet cell metaplasia and mild hyperplasia both before and after treatment. By the application of histochemical and immunohistochemical staining methods it is hoped that the constituents in mucus and specialized cells can be identified.

Topics: Alprostadil; Anti-Ulcer Agents; Duodenal Ulcer; Gastric Mucosa; Gastritis; Humans; Hyperplasia; Misoprostol; Peptic Ulcer; Pyloric Antrum; Random Allocation; Stomach Ulcer