Anesthesiology
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Characterizing the evolution of protein C concentrations in critically ill patients may help in identifying high risk groups and potential therapeutic targets. The authors investigated the time courses of protein C concentrations and their relation to the presence of sepsis, organ dysfunction/failure, and outcome. ⋯ In critically ill surgical patients, protein C concentrations were generally low, associated with organ dysfunction/failure, and independently associated with a higher risk of ICU mortality.
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A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo. ⋯ CNS 7065 is a high-affinity and selective ligand for the benzodiazepine site on the GABAA receptor. CNS 7056 does not show selectivity between GABAA receptor subtypes. CNS 7056 is a potent sedative in rodents with a short duration of action. Inhibition of substantia nigra pars reticulata firing and the inhibition of the effects of CNS 7056 by flumazenil show that it acts at the brain benzodiazepine receptor.
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Bulleyaconitine A (BLA) is an active ingredient of Aconitum bulleyanum plants. BLA has been approved for the treatment of chronic pain and rheumatoid arthritis in China, but its underlying mechanism remains unclear. ⋯ BLA reduces neuronal Na currents strongly at +50 mV in a use-dependent manner. When coinjected with lidocaine or epinephrine, BLA elicits prolonged block of both motor and sensory functions in rats with minimal adverse effects.
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Although the activation-induced intracellular Ca signal is disrupted by sensory neuron injury, the contribution of specific Ca channel subtypes is unknown. ⋯ All high-voltage-activated Ca current subtypes contribute to Ca transients in sensory neurons, although the L-type channel contributes predominantly during prolonged activation. Injury shifts the relative contribution of various Ca channel subtypes to the intracellular Ca transient induced by neuronal activation. Because this effect is cell-size specific, selective therapies might potentially be devised to differentially alter excitability of nociceptive and low-threshold sensory neurons.