Anesthesiology
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The common inhalation anesthetic isoflurane has previously been reported to enhance the aggregation and cytotoxicity of the Alzheimer disease-associated amyloid beta protein (Abeta), the principal peptide component of cerebral beta-amyloid deposits. ⋯ A clinically relevant concentration of isoflurane induces apoptosis, alters APP processing, and increases Abeta production in a human neuroglioma cell line. Because altered processing of APP leading to accumulation of Abeta is a key event in the pathogenesis of Alzheimer disease, these findings may have implications for use of this anesthetic agent in individuals with excessive levels of cerebral Abeta and elderly patients at increased risk for postoperative cognitive dysfunction.
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Most in vitro neuroprotection studies with isoflurane have involved cells obtained during the embryonic or early postnatal period. However, in mature rodents, isoflurane neuroprotection does not persist. The authors determined whether neuroprotection of hippocampal slices with isoflurane decreases with aging and is due to decreased intracellular Ca regulation and survival protein phosphorylation. ⋯ Isoflurane neuroprotection of hippocampal slices during oxygen and glucose deprivation decreases with age. Isoflurane does not prevent large increases in intracellular Ca concentration during oxygen and glucose deprivation and does not induce the phosphorylation of the prosurvival proteins in aging slices. A protein kinase C-mediated increase in NMDAR activity may result in increased excitotoxicity and decreased neuroprotection by volatile anesthetics in the aging brain.
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Endotoxin causes acute lung injury, which can lead to acute respiratory distress syndrome. Because local anesthetics are known to attenuate inflammatory reactions, ropivacaine was tested for its possible antiinflammatory effect in lipopolysaccharide-induced lung injury in rat alveolar epithelial cells (AECs) and rat pulmonary artery endothelial cells (RPAECs) in vitro and in vivo. ⋯ Ropivacaine intervention substantially attenuated the inflammatory response in acute lung injury and thus may carry an interesting potential for antiinflammatory treatment.
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Comparative Study
Major histocompatibility complex haplotype is associated with postherpetic pain in mice.
Postherpetic neuralgia is one of the major complications of herpes zoster caused by the reactivation of varicella-zoster virus and is characterized by severe pain. The authors previously showed the association of a human major histocompatibility complex (MHC) haplotype with postherpetic neuralgia. This study was performed to experimentally confirm the role of MHC haplotype in the development of postherpetic pain using a mouse model of postherpetic pain, which corresponds to postherpetic neuralgia. ⋯ These results suggest that the MHC haplotype (H-2) is involved in the incidence of postherpetic pain, and CD3-positive T cells may play a role in its pathogenesis.
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Myocardial protection by anesthetics is known to involve activation of protein kinase C (PKC). The authors' objective was to identify the PKC isoforms activated by propofol in rat ventricular myocytes. They also assessed the intracellular location of individual PKC isoforms before and after treatment with propofol. ⋯ These results demonstrate that propofol causes an increase in PKC activity in rat ventricular myocytes. Propofol stimulates translocation of PKC-alpha, PKC-delta, PKC-epsilon, and PKC-zeta to distinct intracellular sites in cardiomyocytes. This may be a fundamentally important cellular mechanism of anesthesia-induced myocardial protection in the setting of ischemia-reperfusion injury.