Prostaglandins and chemotherapy-induced ulcers in dogs.

About 50% of patients receiving intrahepatic infusion of 5-fluorouracil deoxyriboside (5-FUDR) for colorectal cancer with hepatic metastasis develop significant gastroduodenal lesions. This paper reviews two studies on the effect of 16,16 dimethyl prostaglandin E2 (DMPGE2) on 5-fluorouracil-induced mucosal lesions in dogs. DMPGE2 at high doses (2 micrograms X kg-1 X h-1), which reduced histamine-stimulated gastric acid secretion by 65%, reduced gastric mucosal injury. Interestingly, DMPGE2 at much lower doses (0.02 micrograms X kg-1 X h-1), which had no effect on histamine-stimulated gastric acid secretion, was also effective in lowering gastric mucosal injury. These animal studies, if supported by the results of a larger patient study, would provide a rational basis for the use of prostaglandins in the prophylaxis and treatment of chemotherapy-induced ulcers.

Prostaglandins, gastroduodenal ulcer and hemorrhagic gastritis.

Today, we have effective and potent drugs such as H2-receptor antagonists for the treatment of peptic ulcers. Cimetidine and ranitidine are antisecretory drugs which heal 67-90% of duodenal ulcers in 4 weeks. Certain prostaglandins (PGs) which also heal gastroduodenal ulcers and hemorrhagic gastritis not only diminish gastric acid secretion but also confer unique protective properties on the gastroduodenal mucosa. This phenomenon of 'cytoprotection' is supported by the experimental finding that PGs prevent gastroduodenal mucosal injury caused by absolute ethanol, HCl, NaOH and other irritating agents. Other PGs which do not reduce gastric acid secretion also heal human gastroduodenal ulcers. These special properties of PGs make them potentially beneficial for the treatment of gastric ulcer, and gastroduodenal ulcers accompanying use of nonsteroidal anti-inflammatory drugs as well as hemorrhagic gastritis which is particularly refractory to other therapeutic modalities.

Viability of some metabolic processes in the isolated toad brain adapted to two osmotic environments.

The viability of the isolated toad brain in an aerated Ringer-like medium has been evaluated by the following criteria: 1) amino acid content before and after incubation; 2) accumulation of amino acids in the incubation medium; 3) a comparison of glucose utilization and [U-14C]glucose metabolism with that occurring in vivo; 4) tissue swelling; and 5) tissue lactate contents. On the basis of these criteria, the isolated toad brain, from toads adapted to a fresh-water or a salt-water environment, retains considerable metabolic integrity for at least 2 hr of incubation at 25 degrees C. Specifically, there was no swelling of the tissue, no apparent accumulation of lactate in the tissue, glucose appeared to be utilized at a rate not too different from that calculated for the toad brain in vivo, and the distribution of label from [U-14C]glucose had an overall pattern which resembled that observed in vivo. The tissue levels of amino acids were generally stable in vitro; however, there was a marked decline in the content of aspartate. The accumulation of amino acids in the medium varied considerably from one amino acid to another. Thus, there was very little net efflux of aspartate, GABA, and glutamate from the tissue but considerable net efflux of glutamine. This efflux of amino acids was greater from brains of hyperosmotically adapted toads than from the brains of toads adapted to fresh water by amounts proportional to their initial tissue contents.

Glutamate uptake by the isolated toad brain.

The isolated toad brain accumulates L-glutamate against strong concentration gradients until a tissue-to-medium concentration ratio of about 3000 : 1 is attained. The accumulated glutamate does not equilibrate with most of the endogenous tissue glutamate but is converted rapidly to glutamine and released into the medium. This mechanism may be involved in the preservation of low extracellular levels of cerebral glutamate.