Anesthesiology
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D-Amino acid oxidase (DAAO) is a flavin adenine dinucleotide-dependent peroxisomal flavoenzyme which is almost exclusively expressed within astrocytes in the spinal cord. DAAO catalyzes oxidation of D-amino acids to hydrogen peroxide, which is a stable and less active reactive oxygen species, and may represent a final form of reactive oxygen species. This study tested the hypothesis that the spinal astroglial DAAO-hydrogen peroxide pathway plays an important role in the development of morphine antinociceptive tolerance. ⋯ For the first time, the authors' result identify a novel spinal astroglial DAAO-hydrogen peroxide pathway that is critically involved in the initiation and maintenance of morphine antinociceptive tolerance, and suggest that this pathway is of potential utility for the management of morphine tolerance and chronic pain.
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Multicenter Study Clinical Trial
Monitoring depth of anesthesia utilizing a combination of electroencephalographic and standard measures.
For decades, monitoring depth of anesthesia was mainly based on unspecific effects of anesthetics, for example, blood pressure, heart rate, or drug concentrations. Today, electroencephalogram-based monitors promise a more specific assessment of the brain function. To date, most approaches were focused on a "head-to-head" comparison of either electroencephalogram- or standard parameter-based monitoring. In the current study, a multimodal indicator based on a combination of both electro encephalographic and standard anesthesia monitoring parameters is defined for quantification of "anesthesia depth." ⋯ A multimodal integration of both standard monitoring and electroencephalographic parameters may more precisely reflect the level of anesthesia compared with monitoring based on one of these aspects alone.
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Recent publications have questioned the validity of the "lipid sink" theory of lipid resuscitation while others have identified sink-independent effects and posed alternative mechanisms such as hemodilution. To address these issues, the authors tested the dose-dependent response to intravenous lipid emulsion during reversal of bupivacaine-induced cardiovascular toxicity in vivo. Subsequently, the authors modeled the relative contribution of volume resuscitation, drug sequestration, inotropy and combined drug sequestration, and inotropy to this response with the use of an in silico model. ⋯ Intravenous lipid emulsion accelerates cardiovascular recovery from bupivacaine toxicity in a dose-dependent manner, which is driven by a cardiotonic response that complements the previously reported sequestration effect.
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The triggering receptor expressed on myeloid cells-1 is an immunoreceptor that amplifies the inflammatory response mediated by toll-like receptors engagement. Triggering receptor expressed on myeloid cells-1 inhibitory peptides such LR12 have been shown to prevent hyperresponsiveness and death in several experimental models of septic shock. ⋯ The triggering receptor expressed on myeloid cells-1 inhibitor LR12 is able to mitigate endotoxin-associated clinical and biological alterations, with no obvious side effects. This study paves the way for future phases Ia and Ib trials in humans.