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Ruei-ming Chen - One of the best experts on this subject based on the ideXlab platform.

  • Ring-Oxidative Biotransformation and Drug Interactions of Propofol in the Livers of Rats
    Hindawi Limited, 2015
    Co-Authors: Yu-ting Tai, Yi Ling Lin, Chia-chen Chang, Yih-giun Cherng, Ming-jaw Don, Ruei-ming Chen
    Abstract:

    Propofol, an Intravenous Anesthetic Agent, is widely used for inducing and maintaining anesthesia during surgical procedures and for sedating intensive care unit patients. In the clinic, rapid elimination is one of the major advantages of propofol. Meanwhile, the biotransformation and drug interactions of propofol in rat livers are still little known. In this study, we evaluated the ring-oxidative metabolism of propofol in phenobarbital-treated rat livers and possible drug interactions. Administration of phenobarbital to male Wistar rats significantly increased levels of hepatic cytochrome P450 (CYP) 2B1/2 and microsomal pentoxyresorufin O-dealkylase (PROD) activity. Analyses by high-performance liquid chromatography and liquid chromatography mass spectroscopy revealed that propofol was metabolized by phenobarbital-treated rat liver microsomes into 4-hydroxypropofol. In comparison, PROD activity and 4-hydroxy-propofol production from propofol metabolism were suppressed by orphenodrine, an inhibitor of CYP2B1/2, and a polyclonal antibody against rat CYP2B1/2 protein. Furthermore, exposure of rats to propofol did not affect the basal or phenobarbital-enhanced levels of hepatic CYP2B1/2 protein. Meanwhile, propofol decreased the dealkylation of pentoxyresorufin by phenobarbital-treated rat liver microsomes in a concentration-dependent manner. Taken together, this study shows that rat hepatic CYP2B1/2 plays a critical role in the ring-oxidative metabolism of propofol into 4-hydroxypropofol, and this Anesthetic Agent can inhibit CYP2B1/2 activity without affecting protein synthesis

  • Mechanisms of ketamine-induced immunosuppression
    Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists, 2012
    Co-Authors: Feng Lin Liu, Ta-liang Chen, Ruei-ming Chen
    Abstract:

    Ketamine, a noncompetitive N-methyl-d-aspartate receptor antagonist, is widely used as an Intravenous Anesthetic Agent. It is known to produce increases in blood pressure and stroke volume, which implies its importance in clinical practice. Ketamine has also been shown to possess anti-inflammatory effects. Our previous studies showed that ketamine, at clinically relevant concentrations, can downregulate endotoxin-induced macrophage activation through toll-like receptor-dependent activation of mitogen-activated protein kinases and the transcription factors nuclear factor-kappa B and activator protein-1. As to the responsible mechanisms, considerable attention was devoted to ketamine-involved regulation of proinflammatory gene expression. The assessment of how ketamine regulates proinflammatory gene expressions is significant in determining the signal cascades that are influenced by this Anesthetic Agent and its clinical application in the tactical use of ketamine in preventing sepsis. Herein, we review the literature on the pharmacodynamics, pharmacokinetics, and possible mechanisms involved in ketamine's immunology.

  • Mechanisms of ketamine-involved regulation of cytochrome P450 gene expression.
    Expert opinion on drug metabolism & toxicology, 2010
    Co-Authors: Jui Tai Chen, Ruei-ming Chen
    Abstract:

    Importance of the field: Ketamine, a widely used Intravenous Anesthetic Agent, is biotransformed by cytochrome P450s (CYPs). Considerable attention is devoted to the ketamine-involved regulation of CYP gene expression. Assessing how ketamine regulates CYP gene expression is significant in recognizing the pharmacology of this Anesthetic Agent and its clinical application.Areas covered in this review: In this review, the authors discuss the effects of ketamine on the regulation of CYP gene expression and its possible mechanisms from the aspects of cytoskeletal remodeling, mitochondrial dysfunction, and alterations of intracellular ATP levels and calcium homeostasis.What the reader will gain: This review may provide readers with more clues for recognizing and avoiding possible ketamine–drug interactions.Take home message: Ketamine may inhibit CYP3A4 expression possibly through reducing calcium mobilization and mitochondrial ATP synthesis and consequently disturbing cytoskeleton remodeling.

  • Molecular mechanisms of propofol-involved suppression of no biosynthesis and inducible iNOS gene expression in LPS-stimulated macrophage-like raw 264.7 cells.
    Shock (Augusta Ga.), 2010
    Co-Authors: Chao Jen Lee, Yu-ting Tai, Yi Ling Lin, Ruei-ming Chen
    Abstract:

    ABSTRACTPropofol (PPF), a widely used Intravenous Anesthetic Agent, has been reported to have immunosuppressive and antioxidative effects. NO plays crucial roles in mediating inflammatory reactions. This study was designed to evaluate the effects of PPF on regulation of iNOS and its possible signal-

  • ketamine inhibits tumor necrosis factor α and interleukin 6 gene expressions in lipopolysaccharide stimulated macrophages through suppression of toll like receptor 4 mediated c jun n terminal kinase phosphorylation and activator protein 1 activation
    Toxicology and Applied Pharmacology, 2008
    Co-Authors: Gongjhe Wu, Ta-liang Chen, Yunefang Ueng, Ruei-ming Chen
    Abstract:

    Abstract Our previous study showed that ketamine, an Intravenous Anesthetic Agent, has anti-inflammatory effects. In this study, we further evaluated the effects of ketamine on the regulation of tumor necrosis factor-α ( TNF-α ) and interlukin-6 ( IL-6 ) gene expressions and its possible signal-transducing mechanisms in lipopolysaccharide (LPS)-activated macrophages. Exposure of macrophages to 1, 10, and 100 μM ketamine, 100 ng/ml LPS, or a combination of ketamine and LPS for 1, 6, and 24 h was not cytotoxic to macrophages. A concentration of 1000 μM of ketamine alone or in combined treatment with LPS caused significant cell death. Administration of LPS increased cellular TNF-α and IL-6 protein levels in concentration- and time-dependent manners. Meanwhile, treatment with ketamine concentration- and time-dependently alleviated the enhanced effects. LPS induced TNF-α and IL-6 mRNA syntheses. Administration of ketamine at a therapeutic concentration (100 μM) significantly inhibited LPS-induced TNF-α and IL-6 mRNA expressions. Application of toll-like receptor 4 (TLR4) small interfering (si)RNA into macrophages decreased cellular TLR4 levels. Co-treatment of macrophages with ketamine and TLR4 siRNA decreased the LPS-induced TNF-α and IL-6 productions more than alone administration of TLR4 siRNA. LPS stimulated phosphorylation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos from the cytoplasm to nuclei. However, administration of ketamine significantly decreased LPS-induced activation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos. LPS increased the binding of nuclear extracts to activator protein-1 consensus DNA oligonucleotides. Administration of ketamine significantly ameliorated LPS-induced DNA binding activity of activator protein-1. Therefore, a clinically relevant concentration of ketamine can inhibit TNF-α and IL-6 gene expressions in LPS-activated macrophages. The suppressive mechanisms occur through suppression of TLR4-mediated sequential activations of c-Jun N-terminal kinase and activator protein-1.

Ta-liang Chen - One of the best experts on this subject based on the ideXlab platform.

  • Mechanisms of ketamine-induced immunosuppression
    Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists, 2012
    Co-Authors: Feng Lin Liu, Ta-liang Chen, Ruei-ming Chen
    Abstract:

    Ketamine, a noncompetitive N-methyl-d-aspartate receptor antagonist, is widely used as an Intravenous Anesthetic Agent. It is known to produce increases in blood pressure and stroke volume, which implies its importance in clinical practice. Ketamine has also been shown to possess anti-inflammatory effects. Our previous studies showed that ketamine, at clinically relevant concentrations, can downregulate endotoxin-induced macrophage activation through toll-like receptor-dependent activation of mitogen-activated protein kinases and the transcription factors nuclear factor-kappa B and activator protein-1. As to the responsible mechanisms, considerable attention was devoted to ketamine-involved regulation of proinflammatory gene expression. The assessment of how ketamine regulates proinflammatory gene expressions is significant in determining the signal cascades that are influenced by this Anesthetic Agent and its clinical application in the tactical use of ketamine in preventing sepsis. Herein, we review the literature on the pharmacodynamics, pharmacokinetics, and possible mechanisms involved in ketamine's immunology.

  • ketamine inhibits tumor necrosis factor α and interleukin 6 gene expressions in lipopolysaccharide stimulated macrophages through suppression of toll like receptor 4 mediated c jun n terminal kinase phosphorylation and activator protein 1 activation
    Toxicology and Applied Pharmacology, 2008
    Co-Authors: Gongjhe Wu, Ta-liang Chen, Yunefang Ueng, Ruei-ming Chen
    Abstract:

    Abstract Our previous study showed that ketamine, an Intravenous Anesthetic Agent, has anti-inflammatory effects. In this study, we further evaluated the effects of ketamine on the regulation of tumor necrosis factor-α ( TNF-α ) and interlukin-6 ( IL-6 ) gene expressions and its possible signal-transducing mechanisms in lipopolysaccharide (LPS)-activated macrophages. Exposure of macrophages to 1, 10, and 100 μM ketamine, 100 ng/ml LPS, or a combination of ketamine and LPS for 1, 6, and 24 h was not cytotoxic to macrophages. A concentration of 1000 μM of ketamine alone or in combined treatment with LPS caused significant cell death. Administration of LPS increased cellular TNF-α and IL-6 protein levels in concentration- and time-dependent manners. Meanwhile, treatment with ketamine concentration- and time-dependently alleviated the enhanced effects. LPS induced TNF-α and IL-6 mRNA syntheses. Administration of ketamine at a therapeutic concentration (100 μM) significantly inhibited LPS-induced TNF-α and IL-6 mRNA expressions. Application of toll-like receptor 4 (TLR4) small interfering (si)RNA into macrophages decreased cellular TLR4 levels. Co-treatment of macrophages with ketamine and TLR4 siRNA decreased the LPS-induced TNF-α and IL-6 productions more than alone administration of TLR4 siRNA. LPS stimulated phosphorylation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos from the cytoplasm to nuclei. However, administration of ketamine significantly decreased LPS-induced activation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos. LPS increased the binding of nuclear extracts to activator protein-1 consensus DNA oligonucleotides. Administration of ketamine significantly ameliorated LPS-induced DNA binding activity of activator protein-1. Therefore, a clinically relevant concentration of ketamine can inhibit TNF-α and IL-6 gene expressions in LPS-activated macrophages. The suppressive mechanisms occur through suppression of TLR4-mediated sequential activations of c-Jun N-terminal kinase and activator protein-1.

  • Ketamine reduces nitric oxide biosynthesis in human umbilical vein endothelial cells by down-regulating endothelial nitric oxide synthase expression and intracellular calcium levels
    Critical care medicine, 2005
    Co-Authors: Ruei-ming Chen, Ta-liang Chen, Yi Ling Lin, Tyng-guey Chen, Yu-ting Tai
    Abstract:

    Objective:Ketamine, an Intravenous Anesthetic Agent, can modulate vascular tone. Nitric oxide (NO), constitutively produced in endothelial cells, contributes to vasoregulation. In this study, we attempted to evaluate the effects of ketamine on NO biosynthesis in human umbilical vein endothelial cell

  • Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine triphosphate synthesis.
    Anesthesiology, 2003
    Co-Authors: Ruei-ming Chen, Yi Ling Lin, Huai-chia Chang, Joen Rong Sheu, Ta-liang Chen
    Abstract:

    BackgroundPropofol is an Intravenous Anesthetic Agent that may impair host defense system. The aim of this study was to evaluate the effects of propofol on macrophage functions and its possible mechanism.MethodsMouse macrophage-like Raw 264.7 cells were exposed to propofol, at 3, 30 (a clinically re

Peter De Paepe - One of the best experts on this subject based on the ideXlab platform.

  • Possible pathogenic mechanism of propofol infusion syndrome involves coenzyme q.
    Anesthesiology, 2015
    Co-Authors: Arnaud Vanlander, Elien De Latter, Georges A. Dacremont, Birgitte Wuyts, Bert Vanheel, Joél Smet, Boel De Paepe, Annick De Jaeger, Juergen Guenther Okun, Peter De Paepe
    Abstract:

    Background: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

  • possible pathogenic mechanism of propofol infusion syndrome involves coenzyme q
    Anesthesiology, 2015
    Co-Authors: Arnaud Vanlander, Elien De Latter, Georges A. Dacremont, Birgitte Wuyts, Bert Vanheel, Joél Smet, Boel De Paepe, Annick De Jaeger, Juergen Guenther Okun, Peter De Paepe
    Abstract:

    Background 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. Methods Eight rats were ventilated and sedated with propofol up to 20 h. Sequential biopsy specimens were taken from liver and skeletal muscle and used for determination of respiratory chain activities and propofol concentration. Activities were also measured in skeletal muscle from a patient who died of propofol infusion syndrome. Results In rats, authors detected a decrease in complex II+III activity starting at low tissue concentration of propofol (20 to 25 µM), further declining at higher concentrations. Before starting anesthesia, the complex II+III/citrate synthase activity ratio in liver was 0.46 (0.25) and in skeletal muscle 0.23 (0.05) (mean [SD]). After 20 h of anesthesia, the ratios declined to 0.17 (0.03) and 0.12 (0.02), respectively. When measured individually, the activities of complexes II and III remained normal. Skeletal muscle from one patient taken in the acute phase of propofol infusion syndrome also shows a selective decrease in complex II+III activity (z-score: -2.96). Conclusion Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.

Yu-ting Tai - One of the best experts on this subject based on the ideXlab platform.

Arnaud Vanlander - One of the best experts on this subject based on the ideXlab platform.

  • Possible pathogenic mechanism of propofol infusion syndrome involves coenzyme q.
    Anesthesiology, 2015
    Co-Authors: Arnaud Vanlander, Elien De Latter, Georges A. Dacremont, Birgitte Wuyts, Bert Vanheel, Joél Smet, Boel De Paepe, Annick De Jaeger, Juergen Guenther Okun, Peter De Paepe
    Abstract:

    Background: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

  • possible pathogenic mechanism of propofol infusion syndrome involves coenzyme q
    Anesthesiology, 2015
    Co-Authors: Arnaud Vanlander, Elien De Latter, Georges A. Dacremont, Birgitte Wuyts, Bert Vanheel, Joél Smet, Boel De Paepe, Annick De Jaeger, Juergen Guenther Okun, Peter De Paepe
    Abstract:

    Background 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. Methods Eight rats were ventilated and sedated with propofol up to 20 h. Sequential biopsy specimens were taken from liver and skeletal muscle and used for determination of respiratory chain activities and propofol concentration. Activities were also measured in skeletal muscle from a patient who died of propofol infusion syndrome. Results In rats, authors detected a decrease in complex II+III activity starting at low tissue concentration of propofol (20 to 25 µM), further declining at higher concentrations. Before starting anesthesia, the complex II+III/citrate synthase activity ratio in liver was 0.46 (0.25) and in skeletal muscle 0.23 (0.05) (mean [SD]). After 20 h of anesthesia, the ratios declined to 0.17 (0.03) and 0.12 (0.02), respectively. When measured individually, the activities of complexes II and III remained normal. Skeletal muscle from one patient taken in the acute phase of propofol infusion syndrome also shows a selective decrease in complex II+III activity (z-score: -2.96). Conclusion Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.