Anesthesiology
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Recent studies of anesthetic-induced unconsciousness in humans have focused predominantly on the intravenous drug propofol and have identified anterior dominance of alpha rhythms and frontal phase-amplitude coupling patterns as neurophysiological markers. However, it is unclear whether the correlates of propofol-induced unconsciousness are generalizable to inhaled anesthetics, which have distinct molecular targets and which are used more commonly in clinical practice. ⋯ In humans, sevoflurane-induced unconsciousness is not correlated with anteriorization of alpha and related cross-frequency patterns, but rather by a disruption of phase-amplitude coupling in the parietal region and phase-phase relationships across the cortex.
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In the senescent heart, the positive inotropic response to β-adrenoceptor stimulation is reduced, partly by dysregulation of β1- and β3-adrenoceptors. The multidrug resistance protein 4 (MRP4) takes part in the control of intracellular cyclic adenosine monophosphate concentration by controlling its efflux but the role of MRP4 in the β-adrenergic dysfunction of the senescent heart remains unknown. ⋯ MRP4 overexpression contributes to the reduction of the positive inotropic response to β-adrenoceptor stimulation in the senescent heart.
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The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures. ⋯ The authors demonstrate the first use of a high-throughput screen to successfully identify a novel anesthetic chemotype and show mammalian anesthetic activity for members of that chemotype.
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Hepcidin is a master regulator of iron metabolism primarily produced by the liver. Markedly increased hepcidin levels have been observed in septic individuals, while decreased hepatic hepcidin expression has been demonstrated in liver diseases that tend to develop into sepsis. However, the role of liver hepcidin in sepsis remains unknown. ⋯ Hepatic hepcidin plays an important role in sepsis through regulation of iron metabolism. The findings may have potential therapeutic implications for liver diseases in which hepcidin expression is decreased.