PubMed Health⌕ Search

Biomedical subjects

R F Derr

Publications and source records attributed to R F Derr.

35 records · Page 2Linked to original sources
PubMed1979

Reversal of ammonia coma in rats by L-dopa: a peripheral effect.

Ammonia coma was produced in rats within 10 to 15 minutes of an intraperitonealinjection of 1.7 mmol NH4CL. This coma was prevented with 1.68 mmol L-dopa given by gastric intubation 15 minutes before the ammonium salt injection. The effect of L-dopa was correlated with a decrease in blood and brain ammonia, an increase in brain dopamine, and an increase in renal excretion of ammonia and urea. Intraventricular infusion of dopamine sufficient to raise the brain dopamine to the same extent did not prevent the ammonia coma nor affect the blood and brain ammonia concentrations. Bilateral nephrectomy eliminated the beneficial effect of L-dopa on blood and brain ammonia and the ammonia coma was not prevented. Thus, the reduction in blood and brain ammonia and the prevention of ammonia coma after L-dopa, can be accounted for by the peripheral effect of dopamine on renal function rather than its central action. These results provide a reasonable explanation for the beneficial effects observed in some encephalopathic patients receiving L-dopa.

Ammonia↗
PubMed1978

Weakness, neuropathy, and coma following total parenteral nutrition in underfed or starved rats: relationship to blood hyperosmolarity and brain water loss.

The continuous infusion of a concentrated, high-caloric glucose solution intravenously into underfed or 3-day-starved rats at a rate of 390 kcal/kg/day results in hypophosphatemia, muscular weakness, neuropathy, lethargy, occasional convulsions, and eventual coma and death. This sequence of events is not observed in similarly infused normal rats. It is a model of a fatal parenteral nutrition syndrome which occurs in undernourished patients. Rats in coma had an eightfold increase in the blood glucose level, a 1.6-fold increase in serum osmolarity, a 16% to 20( decrease in brain water content, and normal blood ketones. A lag phase of at least 8 hr and often 12 to 24 hr occurred following the start of the hyperosmotic glucose infusion before the blood glucose began to accumulate progressively and the syndrome developed. The onset of the syndrome could be prevented by the administration of large amounts of insulin required to keep the blood sugar from exceeding 250 mg/dl. Thus the rat model of the fatal hyperalimentation syndrome is a form of hyperglycemic, hyperosmolar, nonketotic coma caused by brain dehydration.

Animals↗
PubMed1976

Effect of fatty acids on the disposition of ammonia.

Subcoma doses of fatty acids and ammonium salts injected intraperitoneally at the same time into rats or cats act synergistically to produce coma. Under these circumstances, the blood ammonia, is more than double that when the NH4+ is given alone. After these observations a rat liver homogenate system was utilized to study the effect of fatty acids on ammonia utilization in urea, glutamate and glutamine synthesis in vitro. Acetylglutamate-catalyzed urea synthesis was completely inhibited by 45 mM octanoate and was depressed 46% by 9.5 mM octanoate. Citrulline synthesis was similarly inhibited 86 and 28%, respectively. The concentration of liver octanoate at the moment of occurrence of coma after an in vivo injection was approximately 10 mM. The inhibitory effect of fatty acids on the utilization of NH4+ in the urea cycle was greater the longer the fatty acid chain. The critical step in this interference with ammonia metabolism was the inhibition of carbamyl phosphate synthetase. Argininosuccinate synthetase activity was also inhibited to a lesser degree, but ornithine transcarbamylase, argininosuccinate lyase and arginase were unaffected. Glutamate dehydrogenase was likewise inhibited in liver (83%) and brain (43%) by 13 mM octanoate, whereas glutamine synthetase was unaffected. Thus, the two main processes whereby ammonia is metabolized were inhibited by fatty acids at concentrations that exist pathologically, which accounts, at least in part, for the rise in blood ammonia in vivo.

Ammonia↗