Purine metabolites and pyrimidine bases in cerebrospinal fluid of children with simple febrile seizures.

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and pyrimidine bases were determined in the CSF of 18 children after simple febrile seizures and in a control group. There was no statistically significant difference between the two groups for any of these metabolites. This suggests that simple febrile seizures neither significantly disturb the metabolism of nucleotides, nucleosides or bases, nor significantly deplete neuron adenosine triphosphate ATP levels.

Pyrimidine dideoxyribonucleosides: selectivity of penetration into cerebrospinal fluid.

Cerebrospinal fluid (CSF)/plasma ratios of 1 to 30% were obtained in rhesus monkeys for the 3'-azido- and 2',3'-dideoxy-analogs of thymidine, deoxycytidine and deoxyuridine. Penetration of thymidine and deoxyuridine analogs was much greater than for deoxycytidine analogs. Octanol/buffer partition coefficients varied more than 30-fold, but did not correlate with CSF entry. Plasma protein binding was insignificant for all compounds. The presence or absence of the azido group at position 3' did not appear to influence the extent of CSF penetration. Although we do not fully understand the mechanistic basis for the penetration of these nucleosides into the CSF, it is apparent that the structural specificity is related more closely to the nucleobase than the sugar. Based upon elimination rates from the CSF after direct intrathecal injection, the differences in net penetration are determined by influx rather than efflux processes.

Plasma and cerebrospinal fluid nucleosides and oxypurines in acute liver failure.

Concentrations of pyrimidine nucleosides (with the possible exception of uridine) and oxypurines in mammalian plasma and cerebrospinal fluid (CSF) are maintained relatively constant by potent homeostatic mechanisms. To test the importance of the intact liver in maintaining homeostasis of pyrimidine nucleosides and oxypurines in plasma and CSF, we performed a greater than 90% or sham hepatectomy on New Zealand white rabbits. At 1, 6, 12, or 24 hours after real or sham hepatectomy, plasma and CSF nucleosides and oxypurines were measured by high-performance liquid chromatography. At all times after hepatectomy, the concentrations of the pyrimidine deoxyribonucleosides (deoxycytidine, deoxyuridine, and thymidine) were increased approximately threefold in plasma and CSF compared with sham-operated controls. Twenty-four hours after hepatectomy, the concentrations of uridine and cytidine in plasma were decreased by 70% and 50%, respectively, and in CSF by 50% and 40%, respectively, when compared with the concentrations in the sham-operated controls. Hypoxanthine concentrations in CSF were increased approximately twofold at 6, 12, and 24 hours after hepatectomy. These results suggest that liver function is essential for the maintenance of normal concentrations of pyrimidine nucleosides in plasma and CSF. That pyrimidine nucleoside concentrations are disrupted in plasma and CSF in this model of acute liver failure suggests that pools of pyrimidine nucleotides in some tissues (e.g., brain) may be altered by liver failure.