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Glutamate metabolism in rat cortical astrocyte cultures was studied to evaluate the relative rates of flux of glutamate carbon through oxidative pathways and through glutamine synthetase (GS). Rates of 14CO2 production from [1-14C]glutamate were determined, as was the metabolic fate of [14C(U)]glutamate in the presence and absence of the transaminase(More)
Inhibitors of interleukin-1beta converting enzyme (ICE) and a related group of cysteine aspartases of the ICE/ced-3 family inhibit cell death in a variety of settings, including in PC12 cells and sympathetic neurons following withdrawal of trophic support. To assess the particular member(s) of the ICE/ced-3 family that are relevant to cell death and to(More)
We have used cultured PC12 cells and rat sympathetic neurons as model systems to examine the regulation of neuronal cell death and survival. Because nitric oxide (NO) may be involved in nerve growth factor (NGF) signaling in PC12 cells, we tested NO-generating compounds for their ability to protect PC12 cells and sympathetic neurons from death after(More)
Previous studies indicate that activation of c-Jun kinase (JNK) is necessary for apoptosis of trophic factor-deprived PC12 cells and that death in this system is suppressed by multiple agents, including BCL2, inhibitors of the interleukin-1-converting enzyme (ICE) family of proteases, blockers of transcription, and a variety of small molecules with(More)
In the present study, we tested whether apoptotic neuronal death caused by withdrawal of trophic support might be prevented by agents that block cell cycle progression. We used three complementary model systems that exhibit apoptotic death: dividing PC12 cells deprived of nerve growth factor (NGF); and primary cultures of postmitotic sympathetic neurons(More)
Previous studies have demonstrated that multiple agents that promote survival of PC12 cells and sympathetic neurons deprived of trophic support also block cell cycle progression. Presently, we address whether inhibition of cell cycle-related cyclin-dependent kinases (CDKs) prevents neuronal cell death. We show that two distinct CDK inhibitors, flavopiridol(More)
We report that dipyridamole is neuroprotective for a variety of rat embryonic CNS neurons cultured in serum-free basal medium lacking trophic factors or other additives. We also describe the mechanism underlying this action. Neurons died rapidly in basal medium but were rescued in large measure by 10 microM dipyridamole. The protective action of(More)
As we leave behind the assumption of normality in return distributions, the classical risk-reward Sharpe Ratio becomes a questionable tool for ranking risky projects. In the spirit of Sharpe thinking, a more general risk-reward ratio © suitable to compare skewed return distributions with respect to a benchmark, is introduced. This index captures two types(More)