Anesthesiology
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Comparative Study
Functional studies of RYR1 mutations in the skeletal muscle ryanodine receptor using human RYR1 complementary DNA.
Malignant hyperthermia is associated with mutations within the gene encoding the skeletal muscle ryanodine receptor, the calcium channel that releases Ca from sarcoplasmic reticulum stores triggering muscle contraction, and other metabolic activities. More than 200 variants have been identified in the ryanodine receptor, but only some of these have been shown to functionally affect the calcium channel. To implement genetic testing for malignant hyperthermia, variants must be shown to alter the function of the channel. A number of different ex vivo methods can be used to demonstrate functionality, as long as cells from human patients can be obtained and cultured from at least two unrelated families. Because malignant hyperthermia is an uncommon disorder and many variants seem to be private, including the newly identified H4833Y mutation, these approaches are limited. ⋯ The functional assays validate recombinant human skeletal muscle ryanodine receptor for analysis of variants and add an additional mutation (H4833Y) to the repertoire of mutations that can be used for the genetic diagnosis of malignant hyperthermia.
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Comparative Study
Increased genomic copy number of DEFA1/DEFA3 is associated with susceptibility to severe sepsis in Chinese Han population.
Human neutrophil peptides 1-3 are endogenous cationic antimicrobial peptides implicated in host defense against microbes. The genes encoding human neutrophil peptides 1-3 (DEFA1/DEFA3) exhibit copy number variations. This study was designed to determine whether DEFA1/DEFA3 copy number variations conferred susceptibility to infection-induced complications such as severe sepsis. ⋯ DEFA1/DEFA3 is an important genetic component participating in host immune response to severe sepsis. A higher copy number of DEFA1/DEFA3 (>8 copies) is significantly associated with the risk of severe sepsis.
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Comparative Study
Adaptive support ventilation prevents ventilator-induced diaphragmatic dysfunction in piglet: an in vivo and in vitro study.
Contrary to adaptive support ventilation (ASV), prolonged totally controlled mechanical ventilation (CMV) results in the absence of diaphragm activity and causes ventilator-induced diaphragmatic dysfunction. Because maintaining respiratory muscles at rest is likely a major cause of ventilator-induced diaphragmatic dysfunction, ASV may prevent its occurrence in comparison with CMV. The aim of our study was to compare the effects of ASV with those of CMV on both in vivo and in vitro diaphragmatic properties. ⋯ Maintaining diaphragmatic contractile activity by using the ASV mode may protect the diaphragm against the deleterious effect of prolonged CMV, as demonstrated both in vitro and in vivo, in healthy piglets.
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Comparative Study
Effect of PSD-95/SAP90 and/or PSD-93/chapsyn-110 deficiency on the minimum alveolar anesthetic concentration of halothane in mice.
The authors have previously shown that the clinically relevant concentrations of inhalational anesthetics dose-dependently inhibit the postsynaptic density protein (PSD)-95, Dlg, and ZO-1 domain-mediated protein interactions between N-methyl-d-aspartate receptors and PSD-95/synaptic-associated protein (SAP) 90 or PSD-93/Chapsyn-110 and that the knockdown of spinal PSD-95/SAP90 significantly reduces the minimum alveolar concentration (MAC) for isoflurane in rats. ⋯ The current results indicate that PSD-95/SAP90 and PSD-93/Chapsyn-110 are involved in the molecular mechanisms of halothane anesthesia and that the functional role of PSD-95/SAP90 in halothane anesthesia is not enhanced after PSD-93/Chapsyn-110 deletion.
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Comparative Study
Pharmacokinetics of lidocaine, bupivacaine, and levobupivacaine in plasma and brain in awake rats.
We have compared the pharmacokinetics and brain distribution of lidocaine, racemic bupivacaine (bupivacaine), and levobupivacaine in awake, spontaneously breathing rats. ⋯ Although the ratio of total brain concentration to total plasma concentrations of lidocaine, bupivacaine, and levobupivacaine was similar, concentration ratio of bupivacaine in the cerebral extracellular fluid to plasma unbound fraction was significantly higher than lidocaine and levobupivacaine.