Anesthesiology
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Propofol is a short-acting intravenous anesthetic agent. In rare conditions, a life-threatening complication known as propofol infusion syndrome can occur. The pathophysiologic mechanism is still unknown. Some studies suggested that propofol acts as uncoupling agent, others suggested that it inhibits complex I or complex IV, or causes increased oxidation of cytochrome c and cytochrome aa3, or inhibits mitochondrial fatty acid metabolism. Although the exact site of interaction is not known, most hypotheses point to the direction of the mitochondria. ⋯ Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.
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Edoxaban is an oral, selective direct factor Xa inhibitor approved in Japan for venous thromboembolism prevention after orthopedic surgery. Data are lacking regarding reversal strategies for edoxaban; this study assessed whether four-factor prothrombin complex concentrate (Beriplex/Kcentra; CSL Behring GmbH, Marburg, Germany) can effectively reverse its effects on hemostasis using a previously described rabbit model. ⋯ In a rabbit model of hemostasis, four-factor prothrombin complex concentrate administration significantly decreased edoxaban-associated hemorrhage.
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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.