Terry J. Gilbertson

Partial characterization of the gastrointestinal weight changes produced in the female rat by 16,16-dimethylprostaglandin E2

Oral and subcutaneous administration of 16,16-dimethylprostaglandin E2 (16,16-dimethyl PGE2) resulted in an increase in the dry weight of the stomach and small intestine of the female rat. This weight response was rapid, controlled rather than continuously progressing, dose dependent and reversible. The dry weight of the colon also increased but this was not studied in detail. Two-day treatment with 16,16-dimethyl PGE2 caused an increase in the incorporation of 3H-thymidine into the duodenum, jejunum and colon suggesting an increase in cell number. Incorporation into the stomach and ileum was not changed. The number of goblet cells per crypt was increased by prostaglandin treatment in all parts of the small intestine. Since these are mucus producing cells, the small intestine may have increased in cell number and mucus production. Both anti-secretory and cytoprotective doses of 16,16-dimethyl PGE2 caused weight increases in the stomach and small intestine. However, the weight gain by itself was not sufficient to protect the stomach or small intestine from necrotic agents after the prostaglandin was discontinued.

Changes in thymidine uptake in the gastrointestinal tract of the rat following treatment with 16,16-dimethyl prostaglandin E2

Thymidine uptake in the organs of the gastrointestinal tract of the rat was studied to determine if cell synthesis was involved in the increases in weight of the stomach, small intestine and colon which result from treatment with 16,16-dimethyl prostaglandin E2 (16,16-dimethyl PGE2). Animals were treated for 2 days with 16,16-dimethyl PGE2. They were injected with the 3H-thymidine, sacrificed and the organs of interest were removed. The total amount of tritium in the stomach, duodenum, jejunum, ileum, and colon was determined. Thymidine uptake was significantly increased in the duodenum (1.50 times), jejunum (1.53 times), and colon (1.40 times) but not in the stomach and ileum. The increases were dose related in the duodenum and jejunum. The colon showed a similar dose response pattern but the changes with dose did not reach significance. These results confirm and extend a previous report that 16,16-dimethyl PGE2 increased thymidine uptake in the duodenum but not the stomach. This is different from gastrin which has been shown by others to increase thymidine uptake in the stomach, duodenum, ileum and colon.

Hormone changes occurring during second trimester abortion induced with 15(S)-15-methyl prostaglandin F2α

Changes in progesterone, human placental lactogen (HPL), cortisol and estradiol-17B were measured during second trimester abortion induced by I.M. 15-methyl PGF2alpha. A rapid decline in progesterone and HPL was found, indicating perhaps an initial effect on the placenta. A rapid rise in cortisol was found, but it is not clear if this is due to stress or part of the termination mechanism. The changes of estradiol were not as distinct and may reflect opposite effects of the prostaglandin on the placenta and adrenals. Similar hormonal changes were observed regardless of the duration of gestation.

Aspirin-Induced Damage in the Dog Heidenhain Pouch and Cytoprotection with 16,16-Dimethyl PGE2

The gastric mucosa of animals and man can be damaged by noxious agents and protected by prostaglandins. We developed a Heidenhain pouch dog model which allows the study of multiple doses of the protective or noxious agent. Mucosal damage in the pouch caused by instillation of 160 mM aspirin suspended in 150 mM HCl for two 15-min periods was determined by measuring hemoglobin concentration in isotonic mannitol washes. Hemoglobin levels 24 h after the administration of the acid-aspirin suspension were significantly higher than basal levels. Pretreatment with oral doses of 0.3-3 micrograms/kg 16,16-dimethyl PGE2 at 24 and 18 h and 30 min before the acid-aspirin suspension decreased hemoglobin concentrations in the washes (p less than 0.001).

The effect of prostaglandin E2-induced echinocytic transformation on the optassium loss, viscosity and osmotic fragility of normal and sickle cell erythrocytes

Prostaglandin E2 (PGE2)-induced discocyte leads to echinocytic transformation has no effect on the viscosity or osmotic fragility of normal or sickle cell erythrocytes. Membrane permeability, reflected as potassium efflux, is significantly affected in normal erythrocytes when greater than 90% of the cells are morphologically transformed to the echinocytic III stage (PGE2 concentration of 1--2x10(6) ng/ml blood). This potassium loss is significant in sickle erythrocytes when 50-70% of the cell population has been transformed (PGE2 concentration, 5x10(5) ng/ml blood). This change in membrane permeability represents one-half to one-third the flux that occurs with sickling (i.e., greater than 80% of the erythrocytes sickled).