Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Aug 2005
ReviewPotentially neuroprotective and therapeutic properties of nitrous oxide and xenon.
Despite the beneficial effects of prototypical glutamatergic receptor antagonists in animal models, the pharmacological attempts by the use of such agents have met with very limited clinical success because these compounds produce adverse side effects and possess an intrinsic neurotoxicity at neuroprotective and therapeutic concentrations. Interestingly, nitrous oxide and xenon, which are anesthetic gases with a remarkably safe clinical profile, have been shown to be effective inhibitors of the NMDA receptor. We briefly review accumulating evidence that nitrous oxide and xenon at subanesthetic concentrations may have potentially neuroprotective and therapeutic properties, with a particular focus on their beneficial effects on ischemia-induced neuronal death and amphetamine-induced sensitization. ⋯ However, at a higher concentration of 75-vol%, xenon shows potentially neurotoxic properties and adverse side effects. Because both agents are rapidly eliminated from the body, it is plausible that their administration at appropriate subanesthetic neuroprotective and therapeutic concentrations may not be associated, in contrast with prototypical NMDA receptor antagonists, with adverse side effects and potentially neurotoxicity. Finally, the possible therapeutic implications in humans are discussed.
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Ann. N. Y. Acad. Sci. · Aug 2005
Improving predictive modeling in pediatric drug development: pharmacokinetics, pharmacodynamics, and mechanistic modeling.
A workshop was conducted on November 18-19, 2004, to address the issue of improving predictive models for drug delivery to developing humans. Although considerable progress has been made for adult humans, large gaps remain for predicting pharmacokinetic/pharmacodynamic (PK/PD) outcome in children because most adult models have not been tested during development. ⋯ Disease state, as exemplified by obesity, was addressed as a modifier of drug pharmacokinetics and pharmacodynamics during development. Issues addressed in this workshop should be considered in the development of new predictive and mechanistic models of drug kinetics and dynamics in the developing human.
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This study was a retrospective examination of the influence of multimodality neuromonitoring on the incidence of serious brain injury associated with a common type of adult cardiac surgery, coronary artery bypass grafting (CABG). Multichannel EEG, cerebral oximetry, and transcranial Doppler ultrasound were used to detect and correct imbalances in cerebral perfusion and oxygenation. ⋯ With neuromonitoring, the actual observed incidence was 3.0% (P = 0.03). The apparent improvement can be attributed primarily to a reduction in the number of nonembolic diffuse injuries.