The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
Koki Shimoji - One of the best experts on this subject based on the ideXlab platform.
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Thiamylal antagonizes the inhibitory effects of dorsal column stimulation on dorsal horn activities in humans
Neuroscience Research, 2009Co-Authors: Eiichiro Tanaka, Toshiyuki Tobita, Yoshinaka Murai, Yasunori Okabe, Aya Yamada, Tatsuhiko Kano, Hideho Higashi, Koki ShimojiAbstract:Abstract In humans, peripheral somatosensory information converges upon dorsal horn neurons in the spinal cord, which can be recorded from the dorsal epidural space as spinal cord potentials (SCPs) following segmental dorsal root stimulation (SS) employing epidural catheter electrodes. Antidromic action potentials and descending inhibition from the dorsolateral funiculus may contribute to SCPs following dorsal column stimulation (DCS). Effects of Thiamylal (2.5–7.5 mg/kg, i.v.) on SCPs evoked by independent DCS or SS were compared with those evoked by simultaneous DCS and SS (DCS/SS). DCS- and SS-evoked SCPs recorded from the lumbar enlargement consisted of a sharp negative (N) followed by a slow positive (P) potential. Thiamylal induced dose-dependent increases in amplitude and duration of both N and P potentials evoked by DCS and SS, whether the responses were summed or evoked simultaneously. In awake subjects, N and P potentials produced by simultaneous DCS/SS were significantly smaller than the sum of independent responses. Thiamylal anesthesia antagonized this inhibition; responses to simultaneous DCS/SS were larger than the sum of independent responses. These results suggest that in wakefulness DCS inhibits dorsal horn neuron activity in the lumbar spinal cord, while Thiamylal antagonizes DCS-induced inhibition in dose-dependent fashion.
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intravenous anesthetics differentially reduce neurotransmission damage caused by oxygen glucose deprivation in rat hippocampal slices in correlation with n methyl d aspartate receptor inhibition
Critical Care Medicine, 2001Co-Authors: Renzhi Zhan, Kiichiro Taga, Hideyoshi Fujihara, Koki ShimojiAbstract:OBJECTIVE To examine the relation between the effect of intravenous anesthetics on ischemic neurotransmission damage and their actions on N-methyl-d-aspartate (NMDA) receptors in an in vitro cerebral ischemic model. DESIGN Prospective, randomized study in freshly prepared rat hippocampal slices. SETTING University research laboratory. SUBJECTS Hippocampal slices were prepared from male Wistar rats (4-5 wks old). INTERVENTIONS AND MEASUREMENTS In vitro ischemia was induced by exposing slices to glucose-free Krebs solution gassed with 95% N2 /5% CO2 at 37.1-37.3 degrees C. Ischemic neurotransmission damage was indicated by the amplitudes of population spikes (PS) recorded from the CA1 pyramidal layer after stimulation of the Schaffer collaterals. The effect of anesthetics on NMDA receptors was determined by measuring the NMDA-mediated changes in intracellular calcium in the CA1 pyramidal layer with a calcium indicator, fura-2. RESULTS Following 4, 6, and 7.5 mins ischemia in vitro, the recoveries of PS (% control) were 100%, 17.5 +/- 21.8%, and 5.4 +/- 2.1%, respectively. 3-(R)-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 5 microM), an NMDA receptor antagonist, increased the recovery of PS to 88.3 +/- 24.5% after 6 mins ischemia, and to 42.1 +/- 18.7% after 7.5 mins ischemia. Thiopental (400 microM), Thiamylal (400 microM), and ketamine (100 microM), but not propofol (100 microM) and etomidate (10 microM), improved the recovery of PS after 6 and 7.5 mins ischemia; the degrees of their protection were comparable to that of 5 microM CPP. The NMDA-mediated increases in intracellular calcium were almost completely inhibited by Thiamylal, reduced to half by ketamine and thiopental, augmented by propofol, and not affected by etomidate. CONCLUSIONS The results indicate that the efficacy of intravenous anesthetics in attenuating ischemic neuronal damage varies among agents, relating to their effects on NMDA receptors.
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differential inhibitory effects of thiopental Thiamylal and phenobarbital on both voltage gated calcium channels and nmda receptors in rat hippocampal slices
BJA: British Journal of Anaesthesia, 1998Co-Authors: Renzhi Zhan, Naoshi Fujiwara, Tomohiro Yamakura, Kiichiro Taga, Satoru Fukuda, Koki ShimojiAbstract:Although it is known that there are some pharmacological differences between the structurally similar barbiturates, the underlying mechanism of action remains unclear. We have compared the effects of thiopental, Thiamylal and phenobarbital on both voltage-gated calcium channels (VGCC) and N-methyl-D-aspartate (NMDA) receptors in rat hippocampal slices by determining changes in intracellular calcium ([Ca2+]i). Experiments were performed in adult rat hippocampal slices perfused with Krebs solution (37 degrees C). Concentrations of [Ca2+]i in the pyramidal cell layer of the CA1 region were measured using a calcium indicator dye, fura-2. To activate VGCC and NMDA receptors, slices were exposed to K+ 60 mmol litre-1 (
Yutaka Nakaya - One of the best experts on this subject based on the ideXlab platform.
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molecular mechanisms of the inhibitory effects of propofol and Thiamylal on sarcolemmal adenosine triphosphate sensitive potassium channels
Anesthesiology, 2004Co-Authors: Takashi Kawano, Yasuo M Tsutsumi, Shuzo Oshita, Hiroshi Kitahata, Yasuhiro Kuroda, Akira Takahashi, Yoshinobu Tomiyama, Yutaka NakayaAbstract:Background Both propofol and Thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes. Methods The authors used inside-out patch clamp configurations to investigate the effects of propofol and Thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits. Results Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, Thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of Thiamylal. Conclusions These results suggest that the major effects of both propofol and Thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and Thiamylal may influence Kir6.2 activity by different molecular mechanisms; in Thiamylal, the SUR subunit seems to modulate anesthetic sensitivity.
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blockade of adenosine triphosphate sensitive potassium channels by Thiamylal in rat ventricular myocytes
Anesthesiology, 2000Co-Authors: Yasuo M Tsutsumi, Shuzo Oshita, Hiroshi Kitahata, Yasuhiro Kuroda, Takashi Kawano, Yutaka NakayaAbstract:Background: The adenosine triphosphate (ATP)-sensitive potassium (K ATP ) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of Thiamylal on the activities of K ATP channels in isolated rat ventricular myocytes during simulated ischemia. Methods: Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, K ATP channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l Thiamylal. The open probability was determined from current-amplitude histograms. In the inside-out configuration, the current-voltage relation was obtained before and after the application of Thiamylal (50 mg/l). Results: In the cell-attached configuration, 2,4-dinitrophenol caused frequent channel opening. 2,4-Dinitrophenol-induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were K ATP channels. Open probability of K ATP channels was reduced by Thiamylal in a concentration-dependent manner. K ATP channels could be activated in the inside-out configuration because of the absence of ATP. Thiamylal inhibited K ATP channel activity without changing the single-channel conductance. Conclusions: The results obtained in this study indicate that Thiamylal inhibits K ATP channel activities in cell-attached and inside-out patches, suggesting a direct action of this drug on these channels.
Renzhi Zhan - One of the best experts on this subject based on the ideXlab platform.
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intravenous anesthetics differentially reduce neurotransmission damage caused by oxygen glucose deprivation in rat hippocampal slices in correlation with n methyl d aspartate receptor inhibition
Critical Care Medicine, 2001Co-Authors: Renzhi Zhan, Kiichiro Taga, Hideyoshi Fujihara, Koki ShimojiAbstract:OBJECTIVE To examine the relation between the effect of intravenous anesthetics on ischemic neurotransmission damage and their actions on N-methyl-d-aspartate (NMDA) receptors in an in vitro cerebral ischemic model. DESIGN Prospective, randomized study in freshly prepared rat hippocampal slices. SETTING University research laboratory. SUBJECTS Hippocampal slices were prepared from male Wistar rats (4-5 wks old). INTERVENTIONS AND MEASUREMENTS In vitro ischemia was induced by exposing slices to glucose-free Krebs solution gassed with 95% N2 /5% CO2 at 37.1-37.3 degrees C. Ischemic neurotransmission damage was indicated by the amplitudes of population spikes (PS) recorded from the CA1 pyramidal layer after stimulation of the Schaffer collaterals. The effect of anesthetics on NMDA receptors was determined by measuring the NMDA-mediated changes in intracellular calcium in the CA1 pyramidal layer with a calcium indicator, fura-2. RESULTS Following 4, 6, and 7.5 mins ischemia in vitro, the recoveries of PS (% control) were 100%, 17.5 +/- 21.8%, and 5.4 +/- 2.1%, respectively. 3-(R)-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 5 microM), an NMDA receptor antagonist, increased the recovery of PS to 88.3 +/- 24.5% after 6 mins ischemia, and to 42.1 +/- 18.7% after 7.5 mins ischemia. Thiopental (400 microM), Thiamylal (400 microM), and ketamine (100 microM), but not propofol (100 microM) and etomidate (10 microM), improved the recovery of PS after 6 and 7.5 mins ischemia; the degrees of their protection were comparable to that of 5 microM CPP. The NMDA-mediated increases in intracellular calcium were almost completely inhibited by Thiamylal, reduced to half by ketamine and thiopental, augmented by propofol, and not affected by etomidate. CONCLUSIONS The results indicate that the efficacy of intravenous anesthetics in attenuating ischemic neuronal damage varies among agents, relating to their effects on NMDA receptors.
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differential inhibitory effects of thiopental Thiamylal and phenobarbital on both voltage gated calcium channels and nmda receptors in rat hippocampal slices
BJA: British Journal of Anaesthesia, 1998Co-Authors: Renzhi Zhan, Naoshi Fujiwara, Tomohiro Yamakura, Kiichiro Taga, Satoru Fukuda, Koki ShimojiAbstract:Although it is known that there are some pharmacological differences between the structurally similar barbiturates, the underlying mechanism of action remains unclear. We have compared the effects of thiopental, Thiamylal and phenobarbital on both voltage-gated calcium channels (VGCC) and N-methyl-D-aspartate (NMDA) receptors in rat hippocampal slices by determining changes in intracellular calcium ([Ca2+]i). Experiments were performed in adult rat hippocampal slices perfused with Krebs solution (37 degrees C). Concentrations of [Ca2+]i in the pyramidal cell layer of the CA1 region were measured using a calcium indicator dye, fura-2. To activate VGCC and NMDA receptors, slices were exposed to K+ 60 mmol litre-1 (
Takashi Kawano - One of the best experts on this subject based on the ideXlab platform.
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effects of propofol and Thiamylal on nicorandil induced atp sensitive potassium channel activities in cultured rat aortic smooth muscle cells
Masui. The Japanese journal of anesthesiology, 2005Co-Authors: Satoru Eguchi, Shuzo Oshita, Takashi Kawano, Nobuyoshi NakajoAbstract:BACKGROUND: Nicorandil, a hybrid ATP-sensitive potassium (K(ATP)) channel opener and nitrate compound, is used clinically for the treatment of angina pectoris. In the present study, we investigated the effects of propofol and Thiamylal on sarcolemmal K(ATP) channels activities induced by nicorandil in cultured rat aortic smooth muscle cells. METHODS: We used inside-out patch clamp configurations to investigate the effects of propofol and Thiamylal on nicorandil induced K(ATP) channel activities. RESULTS: K(ATP) channel was not spontaneously activated by patch excision in the absence of intracellular ATP. Application of nicorandil (100 microM) induced a marked activation of KATP channel currents, which was completely blocked by 3 microM glibenclamide, the sulfonylurea that blocks K(ATP) channels. Nicorandil induced KATP channel currents were not significantly inhibited by application of 10 and 100 microM propofol to intracellular surface. However, application of 100 and 300 microM Thiamylal to intracellular surface significantly inhibited the nicorandil induced K(ATP) channel currents, with relative channel activities decreasing to 0.65 +/- 0.08 and 0.46 +/- 0.10 of control, respectively. CONCLUSIONS: Propofol had no effect on nicorandil induced sarcolemmal KATP channel activities in rat aortic smooth muscle cells, whereas Thiamylal significantly inhibited these channel activities at clinically relevant concentrations.
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molecular mechanisms of the inhibitory effects of propofol and Thiamylal on sarcolemmal adenosine triphosphate sensitive potassium channels
Anesthesiology, 2004Co-Authors: Takashi Kawano, Yasuo M Tsutsumi, Shuzo Oshita, Hiroshi Kitahata, Yasuhiro Kuroda, Akira Takahashi, Yoshinobu Tomiyama, Yutaka NakayaAbstract:Background Both propofol and Thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes. Methods The authors used inside-out patch clamp configurations to investigate the effects of propofol and Thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits. Results Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, Thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of Thiamylal. Conclusions These results suggest that the major effects of both propofol and Thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and Thiamylal may influence Kir6.2 activity by different molecular mechanisms; in Thiamylal, the SUR subunit seems to modulate anesthetic sensitivity.
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blockade of adenosine triphosphate sensitive potassium channels by Thiamylal in rat ventricular myocytes
Anesthesiology, 2000Co-Authors: Yasuo M Tsutsumi, Shuzo Oshita, Hiroshi Kitahata, Yasuhiro Kuroda, Takashi Kawano, Yutaka NakayaAbstract:Background: The adenosine triphosphate (ATP)-sensitive potassium (K ATP ) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of Thiamylal on the activities of K ATP channels in isolated rat ventricular myocytes during simulated ischemia. Methods: Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, K ATP channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l Thiamylal. The open probability was determined from current-amplitude histograms. In the inside-out configuration, the current-voltage relation was obtained before and after the application of Thiamylal (50 mg/l). Results: In the cell-attached configuration, 2,4-dinitrophenol caused frequent channel opening. 2,4-Dinitrophenol-induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were K ATP channels. Open probability of K ATP channels was reduced by Thiamylal in a concentration-dependent manner. K ATP channels could be activated in the inside-out configuration because of the absence of ATP. Thiamylal inhibited K ATP channel activity without changing the single-channel conductance. Conclusions: The results obtained in this study indicate that Thiamylal inhibits K ATP channel activities in cell-attached and inside-out patches, suggesting a direct action of this drug on these channels.
Yasuo M Tsutsumi - One of the best experts on this subject based on the ideXlab platform.
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Anesthetic management of a patient with methylmalonic acidemia: a case report
SpringerOpen, 2018Co-Authors: Yuta Uemura, Nami Kakuta, Katsuya Tanaka, Yasuo M TsutsumiAbstract:Abstract Background Methylmalonic acidemia (MMA) is a metabolic disorder of organic acids and is characterized by the accumulation of methylmalonic acids. Case presentation The patient was a 19-year-old female diagnosed with severe MMA at 3 days of age, who was scheduled for renal replacement therapy. Preoperatively, there was no evidence of metabolic acidosis or electrolyte abnormalities. Glucose was administered preoperatively following a 6-h fast. Anesthesia was administered using Thiamylal, remifentanil, rocuronium, and sevoflurane. After tracheal intubation, the patient underwent an ultrasound-guided bilateral rectus sheath block with ropivacaine. A drop in blood sugar level was treated with 5% glucose. Extubation was performed after intravenous administration of sugammadex. Conclusions We report the anesthetic management of a patient with MMA using a combination of general anesthesia and rectus sheath block
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molecular mechanisms of the inhibitory effects of propofol and Thiamylal on sarcolemmal adenosine triphosphate sensitive potassium channels
Anesthesiology, 2004Co-Authors: Takashi Kawano, Yasuo M Tsutsumi, Shuzo Oshita, Hiroshi Kitahata, Yasuhiro Kuroda, Akira Takahashi, Yoshinobu Tomiyama, Yutaka NakayaAbstract:Background Both propofol and Thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes. Methods The authors used inside-out patch clamp configurations to investigate the effects of propofol and Thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits. Results Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, Thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of Thiamylal. Conclusions These results suggest that the major effects of both propofol and Thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and Thiamylal may influence Kir6.2 activity by different molecular mechanisms; in Thiamylal, the SUR subunit seems to modulate anesthetic sensitivity.
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blockade of adenosine triphosphate sensitive potassium channels by Thiamylal in rat ventricular myocytes
Anesthesiology, 2000Co-Authors: Yasuo M Tsutsumi, Shuzo Oshita, Hiroshi Kitahata, Yasuhiro Kuroda, Takashi Kawano, Yutaka NakayaAbstract:Background: The adenosine triphosphate (ATP)-sensitive potassium (K ATP ) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of Thiamylal on the activities of K ATP channels in isolated rat ventricular myocytes during simulated ischemia. Methods: Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, K ATP channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l Thiamylal. The open probability was determined from current-amplitude histograms. In the inside-out configuration, the current-voltage relation was obtained before and after the application of Thiamylal (50 mg/l). Results: In the cell-attached configuration, 2,4-dinitrophenol caused frequent channel opening. 2,4-Dinitrophenol-induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were K ATP channels. Open probability of K ATP channels was reduced by Thiamylal in a concentration-dependent manner. K ATP channels could be activated in the inside-out configuration because of the absence of ATP. Thiamylal inhibited K ATP channel activity without changing the single-channel conductance. Conclusions: The results obtained in this study indicate that Thiamylal inhibits K ATP channel activities in cell-attached and inside-out patches, suggesting a direct action of this drug on these channels.
