16-16-dimethylprostaglandin-e2 and Hyperplasia

We studied the effects of the oral administration of a stable prostaglandin E2 analog, 16,16-dimethyl prostaglandin E2, on the intrahepatic biliary branches in a canine model. Obstructive cholestasis with a bacterial infection was induced surgically in two liver lobes in healthy mongrel dogs, and 16,16-dimethyl prostaglandin E2 was administered orally. We examined the morphological changes in the intrahepatic biliary branches and quantitatively estimated density of mucus-producing glandular elements in the ductal wall by counting these glands per unit area. Dogs treated with 16,16-dimethyl prostaglandin E2 (group 1) demonstrated fibrous thickening of the ductal wall, moderate infiltration by inflammatory cells and severe adenomatous hyperplasia of the bile duct epithelium, including striking proliferation of the mucous glands. The mean number of these mucous glands per unit area (4 mm2) was 43.0 +/- 9.0 (mean +/- S.D.; range = 36 to 56). In contrast, in a control group whose members did not receive 16,16-dimethyl prostaglandin E2 (group 2), the mean number of mucous glands per unit area was 19.4 +/- 8.0 (range = 10 to 29), significantly lower than that in group 1, although histological examination revealed chronic inflammation in the region of the large bile duct similar to that in group 1. These findings suggest that the increase in the number of mucous glands that typically occur in the setting of bile stasis and biliary infection is enhanced by 16,16-dimethyl prostaglandin E2.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Bacteroides Infections; Bile Ducts, Intrahepatic; Cholestasis, Intrahepatic; Dogs; Escherichia coli Infections; Exocrine Glands; Female; Hyperplasia; Inflammation; Male; Mucus

Survival following massive resection of the small intestine is often possible due to substantial hyperplasia of the mucosal surface in the remaining small intestine. While nutrients provide the major stimulus for hyperplasia in the clinical setting, the availability of drugs to augment this process would have obvious therapeutic implications. We evaluated the ability of 16,16-dimethyl-prostaglandin E2 (PGE2 to augment mucosal hyperplasia following massive small bowel resection in the rat. Three groups of 7 Sprague-Dawley rats, 160 g body weight, were subjected to 70% jejunoileal resection. One group was given 150 micrograms/kg of 16,16-dimethyl-PGE2 intragastrically twice daily, a second group 75 micrograms/kg subcutaneously, and a third group was untreated. After 17 days, segmental evaluation of mucosal mass in the remaining small intestine was determined by measuring mucosal protein, DNA, and disaccharidase levels. A significantly greater increase in mucosal mass was developed in the duodenum proximal to the anastomosis in both treatment groups, but neither the proximal nor distal ileum demonstrated significantly more adaptation. Histological examination in the duodenum confirmed the presence of a greater adaptive response in both the intragastrically and subcutaneously treated animals. 16,16-dimethyl-PGE2 appears to augment mucosal adaptation following massive small bowel resection in the rat, primarily in the very proximal small intestine.

Topics: 16,16-Dimethylprostaglandin E2; Adaptation, Physiological; alpha-Glucosidases; Animals; Hyperplasia; Injections, Subcutaneous; Intestinal Mucosa; Intestine, Small; Male; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains

In adult rats topical application of 16,16-dm PGE2 (PGE) every 8 h for three weeks led to a dose-dependent increase of the height of the gastric and duodenal mucosa, especially pronounced in the antrum (+115% with the high dose). In the gastric corpus this resulted from an enlargement of the lamina propria and the epithelial cell mass, the latter mainly from a hyperplasia of the surface and foveolar mucous cells. In contrast, the number of parietal cells was not affected. These findings were corroborated by the observation that an increase of antral mucosal height was also induced by a similar parenteral PGE treatment regimen (dosage 25 micrograms/kg). Both longterm intragastric and intraperitoneal PGE treatment led to an increase in DNA synthesis within the mucosa of the gastric antrum and corpus by 19 to 74%. In a third study 25 or 100 micrograms/kg of PGE applied every 8 h intragastrically to 10 suckling rats from the 7th to 11th postnatal day resulted in a dose-dependent increase in the length of the villi and the disaccharidase activities (30-630%). These studies suggest that 16,16-dm PGE2 exhibits a trophic effect on both the stomach and the small bowel.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Dose-Response Relationship, Drug; Female; Gastric Mucosa; Hyperplasia; Hypertrophy; Intestinal Mucosa; Intestine, Small; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stimulation, Chemical; Time Factors

We performed acid secretory and histomorphometric studies in rats treated intragastrically with a regimen of 100 micrograms/kg or 5 micrograms/kg of 16,16-dimethyl prostaglandin E2, or of saline every 8 h for 21 days. All animals given the high-dose treatment developed a macroscopically visible enlargement of the ridge at the corpus-forestomach border, due to an increase in connective tissue and epithelial cell layer. Mucosal thickness was significantly increased in all parts of the stomach, the duodenum, and the proximal colon, but most markedly in the gastric antrum (+115%), where it was accompanied by a higher mitotic rate and hyperplasia of surface and foveolar mucous cells. Within the oxyntic area (corpus), high-dose prostaglandin treatment led to an increase in the number of surface and foveolar mucous cells and chief cells. In contrast, both the number of parietal cells and maximal acid output were not influenced. It is unlikely that the hyperplasia of gastric mucosa is mediated by gastrin since gastrin has no trophic effects on the rat antrum and disproportionally increases the parietal cell number of the oxyntic gastric glands.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Antacids; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Hyperplasia; Intestinal Mucosa; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Time Factors