Anesthesia and analgesia
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Anesthesia and analgesia · Aug 2008
Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor.
Palonosetron is a 5-HT(3)-receptor antagonist (5-HT(3)-RA) that has been shown to be superior to other 5-HT(3)-RAs in phase III clinical trials for the prevention of acute, delayed, and overall chemotherapy-induced nausea and vomiting. The improved clinical efficacy of palonosetron may be due, in part, to its more potent binding and longer half-life. However, these attributes alone are not sufficient to explain the results with palonosetron. We sought to elucidate additional differences among 5-HT(3)-RAs that could help explain the observations in the clinic. ⋯ Palonosetron exhibited allosteric binding and positive cooperativity when binding to the 5-HT(3) receptor. Palonosetron also triggered functional effects that persisted beyond its binding to the 5-HT(3) receptor at the cell surface. Differences in binding and effects on receptor function may be relevant to the unique beneficial actions of palonosetron. To our knowledge, this is the first report showing palonosetron's interaction with the 5-HT(3) receptor at the molecular level, clearly differentiating it from other 5-HT(3)-RAs.
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Anesthesia and analgesia · Aug 2008
Modulators of calcium influx regulate membrane excitability in rat dorsal root ganglion neurons.
Chronic neuropathic pain resulting from neuronal damage remains difficult to treat, in part, because of incomplete understanding of underlying cellular mechanisms. We have previously shown that inward Ca2+ flux (I(Ca)) across the sensory neuron plasmalemma is decreased in a rodent model of chronic neuropathic pain, but the direct consequence of this loss of I(Ca) on function of the sensory neuron has not been defined. We therefore examined the extent to which altered membrane properties after nerve injury, especially increased excitability that may contribute to chronic pain, are attributable to diminished Ca2+ entry. ⋯ Taken together, our findings show that suppression of I(Ca) decreases the AHP, reduces the hyperpolarization-induced voltage sag, and increases excitability in sensory neurons, replicating changes that follow peripheral nerve trauma. This suggests that the loss of I(Ca) previously demonstrated in injured sensory neurons contributes to their dysfunction and hyperexcitability, and may lead to neuropathic pain.
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Anesthesia and analgesia · Aug 2008
The effects of auditory evoked potential click sounds on bispectral index and entropy.
The click sounds of auditory evoked potentials (AEP) might have some effect on electroencephalogram indices and Bispectral Index (BIS) but many studies, unconcerned about this effect, have measured both indices simultaneously. In this study, I examined the effects, of AEP click sounds on the BIS, and also on the response entropy (RE) and state entropy (SE) of the entropy monitor. ⋯ AEP monitor click sounds transiently increased the simultaneously measured BIS, RE, and SE during different levels of sedation by propofol infusion during spinal anesthesia. Therefore, the effects of the click sounds should be considered when these monitors are used simultaneously in the same patient.
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Anesthesia and analgesia · Aug 2008
Intravenous dexmedetomidine decreases lung permeability induced by intracranial hypertension in rats.
Intracisternal dexmedetomidine (Dex) attenuates cardiac dysfunction in rats with intracranial hypertension (ICH). However, the effects of IV Dex on cardiac function and lung permeability during ICH have not been evaluated. We tested the hypothesis that IV Dex attenuates hemodynamic changes and decreases lung permeability induced by ICH in rats. ⋯ Prophylactic IV Dex decreases lung permeability as well as hemodynamic changes induced by ICH in rats.