Yoshinori Kamiya | Uonuma institute of community medicine, Niigata University Hospital (original) (raw)
Papers by Yoshinori Kamiya
Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lyi... more Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 um in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons ...
Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lyi... more Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 um in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons ...
Pfl�gers Archiv European Journal of Physiology, 1998
The authors studied effects of opioid receptor agonists on neuronal nicotinic-receptor-mediated c... more The authors studied effects of opioid receptor agonists on neuronal nicotinic-receptor-mediated current in PC12 cells using whole-cell current recording. At 1 µM, [D-Ala, N-Me, Phe, Gly-ol]-enkephalin (DAMGO), a selective µ receptor agonist, or 10 µM methionine-enkephalin, a µ and δ receptor agonist, did not inhibit the current elicited by 30 µM nicotine significantly. Dynorphin A (1-17) (0.1-1 µM), an endogenous κ receptor agonist, and U50488 (0.1-10 µM), a non-peptide selective κ receptor agonist, depressed the nicotine-induced current reversibly in a dose-dependent manner. They accelerated the current decay, resulting in greater effects on the nondesensitized current than the peak current. These effects were not affected by nor-binaltrophimine, a selective κ receptor antagonist, or by inclusion of guanosine 5′-O-(2-thiobiphosphate) (GDP[β-S]), a GTP binding protein blocker, into the pipette solution. These results demonstrate that two κ opioid receptor agonists, dynorphin A (1-17) and U50488, inhibit neuronal nicotinic-receptormediated current without the involvement of opioid receptors or GTP binding proteins. The acceleration of the current decay suggests a direct action on nicotinic receptors such as open channel block, or augmentation of desensitization. Modulation of neuronal nicotinic receptors by dynorphins may play a role in some areas where dynorphin release sites and neuronal nicotinic receptors are colocalized.
European Journal of Anaesthesiology, 2005
0.5 mM and more, the phase transition temperature decreased to 40°C and below, which meant the lo... more 0.5 mM and more, the phase transition temperature decreased to 40°C and below, which meant the lowering of the membrane viscosity. Conclusion(s): In the clinical concentration of sevo and iso, viscosity of the phospholipid membrane was not almost changed. This result may support the recent findings that phospholipid membrane is not the major action site by volatile anesthetics.
PLOS ONE, 2021
Yokukansan (YKS) is a traditional Japanese herbal (Kampo) medicine prescribed for anxiety. In thi... more Yokukansan (YKS) is a traditional Japanese herbal (Kampo) medicine prescribed for anxiety. In this randomized controlled trial, we compared the subjective assessment of anxiety using questionnaires and its objective assessment using salivary alpha-amylase concentrations in YKS and control (CNT) groups of women undergoing breast surgery. The trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000028998), and the investigators were blinded to drug administration. One hundred patients who underwent breast cancer surgery were allocated to either the YKS or the CNT group. Finally, 35 and 42 patients in the YKS and CNT groups were analyzed, respectively. The YKS group received two 2.5 g doses of the medication before sleeping on the night before surgery and 2 h before inducing anesthesia, while the CNT group did not receive medication preoperatively. Patients answered two questionnaires, the Hospital Anxiety and De...
Brain research, Mar 1, 2018
We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord ... more We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as eviden...
JA Clinical Reports, 2017
Background: A scalp block or wound infiltration of local anesthetic is thought to effectively con... more Background: A scalp block or wound infiltration of local anesthetic is thought to effectively control post-craniotomy pain. However, it can result in local anesthetic toxicity (LAST), which is difficult to distinguish from brain damage due to the surgical procedure when emergence from general anesthesia is delayed. Lipid rescue (infusion of a lipid emulsion) is a widely accepted treatment for LAST. Case presentation: A 64-year-old man underwent surgical resection of a glioma in the brainstem. While still under general anesthesia, and before suturing of the wound, he received a 20-mL scalp infusion of ropivacaine 0.75%. His emergence from anesthesia was delayed, his respiration was suppressed, and premature ventricular contractions occurred; all of which are symptoms of LAST. Injection of a 20% lipid emulsion rapidly alleviated these symptoms. Interestingly, the blood concentration of ropivacaine increased after lipid rescue. Conclusions: The increase in ropivacaine concentration in the blood after lipid rescue suggests that the intravenously administered lipid emulsion absorbed the ropivacaine from the intoxicated brain and heart tissue. This finding is consistent with the lipid sink theory as a mechanistic explanation of lipid rescue.
JA Clinical Reports, 2015
Background: Acute postoperative pain is an integral risk factor in the development of chronic pai... more Background: Acute postoperative pain is an integral risk factor in the development of chronic pain after breast cancer surgery (BCS). Pectoral nerve block (PECSB) has been recently reported as an analgesic method for BCS. Here, we retrospectively compared intraoperative opioid requirement, postoperative pain after BCS, and incidence of postoperative nausea and vomiting (PONV) in patients who underwent BCS under total intravenous anesthesia (TIVA) with or without PECSB. Findings: We reviewed anesthesia charts and medical records of 146 patients who underwent BCS at Niigata University Medical and Dental Hospital from January 2013 to March 2014; 36 patients were included in the TIVA group, and 35 patients were included in the TIVA + PECSB group. Intraoperative remifentanil requirements were significantly lower in the TIVA + PECSB group than in the TIVA group, and the cumulative distribution of remifentanil was reduced in patients who received PECSB (TIVA: 10.9 ± 2.9 μg/kg/h; TIVA + PECSB: 7.3 ± 3.3 μg/kg/h; p < 0.001). Postoperative pain scores during the 48 h after surgery were significantly lower in the TIVA + PECSB group than in the TIVA group (TIVA: 2 [1-5]; TIVA + PECSB: 1 [0-5]; p = 0.03). However, administration of fentanyl during operation, percentage of patients requiring supplemental analgesics, and incidence of PONV were not significantly different between groups. Conclusions: PECSB significantly reduced intraoperative remifentanil usage and postoperative pain. However, the requirement for postoperative supplemental analgesics and the incidence of PONV did not differ. These data suggested that PECSB may be useful for perioperative pain management in patients undergoing BCS.
JA Clinical Reports, 2015
Background: Analgesia after Cesarean delivery (CD) requires early ambulation to prevent thromboem... more Background: Analgesia after Cesarean delivery (CD) requires early ambulation to prevent thromboembolic disease and to facilitate baby care. We retrospectively reviewed anesthesia charts and medical records of patients who underwent CD to compare the efficacy of spinal anesthesia supplemented with intrathecal morphine hydrochloride (ITM) and combined spinal-epidural anesthesia followed by opioid-free epidural analgesia (CSEA-EDA). Findings: All subjects underwent CD at Nagaoka Chuo General Hospital between February 2012 and January 2013. Patient characteristics, time to first analgesic rescue after CD, and analgesic use after CD were examined. Incidences of postural hypotension, lower extremity numbness/weakness, postoperative nausea/vomiting (PONV), and pruritus were also examined for 48 h after CD. Average time to first analgesic use after CD (ITM 25.13 ± 16.07 h, CSEA-EDA 22.42 ± 16.27 h, p = 0.521) and cumulative probability of rescue analgesic use (p = 0.139 by log-rank test) were comparable between groups. However, average analgesic use within 24 h was lower in the ITM group (0.75 ± 1.05 times) than in the CSEA-EDA group (1.52 ± 1.72 times, p = 0.0497). Numbness or motor weakness in lower extremities only occurred in the CSEA-EDA group, and pruritus only occurred in the ITM group. Conclusions: The results of this study suggest that ITM is better than CSEA-EDA for anesthesia following CD with regard to pain control. Also, ITM would be advantageous for early ambulation following CD because of lower incidence of numbness and motor weakness in lower extremities compared to CSEA-EDA.
JA Clinical Reports, 2015
Background: Analgesia after Cesarean delivery (CD) requires early ambulation to prevent thromboem... more Background: Analgesia after Cesarean delivery (CD) requires early ambulation to prevent thromboembolic disease and to facilitate baby care. We retrospectively reviewed anesthesia charts and medical records of patients who underwent CD to compare the efficacy of spinal anesthesia supplemented with intrathecal morphine hydrochloride (ITM) and combined spinal-epidural anesthesia followed by opioid-free epidural analgesia (CSEA-EDA). Findings: All subjects underwent CD at Nagaoka Chuo General Hospital between February 2012 and January 2013. Patient characteristics, time to first analgesic rescue after CD, and analgesic use after CD were examined. Incidences of postural hypotension, lower extremity numbness/weakness, postoperative nausea/vomiting (PONV), and pruritus were also examined for 48 h after CD. Average time to first analgesic use after CD (ITM 25.13 ± 16.07 h, CSEA-EDA 22.42 ± 16.27 h, p = 0.521) and cumulative probability of rescue analgesic use (p = 0.139 by log-rank test) were comparable between groups. However, average analgesic use within 24 h was lower in the ITM group (0.75 ± 1.05 times) than in the CSEA-EDA group (1.52 ± 1.72 times, p = 0.0497). Numbness or motor weakness in lower extremities only occurred in the CSEA-EDA group, and pruritus only occurred in the ITM group. Conclusions: The results of this study suggest that ITM is better than CSEA-EDA for anesthesia following CD with regard to pain control. Also, ITM would be advantageous for early ambulation following CD because of lower incidence of numbness and motor weakness in lower extremities compared to CSEA-EDA.
Journal of Pharmacological Sciences, 2010
Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite ... more Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for axonal transport has been lacking. In order to better characterize the molecular mechanisms involved in axonal transport, we here developed a computer-assisted monitoring system. Using lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine (CM-DiI) as a labeling dye, we have successfully labeled membranous organelles in cultured chick dorsal root ganglia neurons. We confirmed that sodium azide, an ATPase inhibitor, and nocodazole, a microtubule-destabilizing agent, markedly suppressed anterograde and retrograde axonal transport of CM-DiI-labeled particles. We further tested the effects of several anti-neoplastic drugs on axonal transport. Paclitaxel, vincristine, cisplatin, and oxaliplatin, all of which are known to be neurotoxic and to cause neurological symptoms, suppressed anterograde and retrograde axonal transport. Another series of anti-neoplastic drugs, including methotrexate and 5-fluorouracil, did not affect the axonal transport. This is the first report of an automated monitoring system for axonal transport. This system will be useful for toxicity assays, characterizing axonal transport, or screening drugs that may modify neuronal functions.
The Journal of Emergency Medicine, 2013
Background: Therapeutic hypothermia (TH) is one of the key treatments after cardiac arrest (CA). ... more Background: Therapeutic hypothermia (TH) is one of the key treatments after cardiac arrest (CA). Selection of post-CA patients for TH remains problematic, as there are no clinically validated tools to determine who might benefit from the therapy. Objective: The aim of this study was to investigate retrospectively whether laboratory findings or other patient data obtained during the early phase of hospital admission could be correlated with neurological outcome after TH in comatose survivors of CA. Methods: Medical charts of witnessed CA patients admitted between June 2003 and July 2009 who were treated with TH were reviewed retrospectively. The subjects were grouped based on their cerebral performance category (CPC) 6 months after CA, as either good recovery (GR) for CPC 1-2 or non-good recovery (non-GR) for CPC 3-5. The following well-known determinants of outcome obtained during the early phase of hospital admission were evaluated: age, gender, body mass index, cardiac origin, presence of ventricular fibrillation (VF), time from collapse to cardiopulmonary resuscitation, time from collapse to return of spontaneous circulation, body temperature, arterial blood gases, and blood test results. Results: We analyzed a total of 50 (25 GR and 25 non-GR) patients. Multivariate logistic analysis showed that initial heart rhythm and pH levels were significantly higher in the GR group than in the non-GR group (ventricular tachycardia/VF rate: p = 0.055, 95% confidence interval [CI] 0.768-84.272, odds ratio [OR] 8.047; pH: 7.155 ± 0.139 vs. 6.895 ± 0.100, respectively, p < 0.001, 95% CI 1.838-25.827; OR 6.89). Conclusion: These results imply that in addition to initial heart rhythm, pH level may be a good candidate for neurological outcome predictor even though previous research has found no correlation between initial pH value and neurological outcome. Crown
Journal of Biological Chemistry, 2005
Journal of Biological Chemistry, 2009
The ductus arteriosus (DA), an essential vascular shunt for fetal circulation, begins to close im... more The ductus arteriosus (DA), an essential vascular shunt for fetal circulation, begins to close immediately after birth. Although Ca 2؉ influx through several membrane Ca 2؉ channels is known to regulate vasoconstriction of the DA, the role of the T-type voltage-dependent Ca 2؉ channel (VDCC) in DA closure remains unclear. Here we found that the expression of ␣1G, a T-type isoform that is known to exhibit a tissue-restricted expression pattern in the rat neonatal DA, was significantly upregulated in oxygenated rat DA tissues and smooth muscle cells (SMCs). Immunohistological analysis revealed that ␣1G was localized predominantly in the central core of neonatal DA at birth. DA SMC migration was significantly increased by ␣1G overexpression. Moreover, it was decreased by adding ␣1G-specific small interfering RNAs or using R(؊)-efonidipine, a highly selective T-type VDCC blocker. Furthermore, an oxygenationmediated increase in an intracellular Ca 2؉ concentration of DA SMCs was significantly decreased by adding ␣1G-specific siRNAs or using R(؊)-efonidipine. Although a prostaglandin E receptor EP4 agonist potently promoted intimal thickening of the DA explants, R(؊)-efonidipine (10 ؊6 M) significantly inhibited EP4-promoted intimal thickening by 40% using DA tissues at preterm in organ culture. Moreover, R(؊)-efonidipine (10 ؊6 M) significantly attenuated oxygenation-induced vasoconstriction by ϳ27% using a vascular ring of fetal DA at term. Finally, R(؊)-efonidipine significantly delayed the closure of in vivo DA in neonatal rats. These results indicate that T-type VDCC, especially ␣1G, which is predominantly expressed in neonatal DA, plays a unique role in DA closure, implying that T-type VDCC is an alternative therapeutic target to regulate the patency of DA. The ductus arteriosus (DA) 2 is an essential vascular shunt between the aortic arch and the pulmonary trunk during a fetal period (1). After birth, the DA closes immediately in accordance with its smooth muscle contraction and vascular remodeling, whereas the connecting vessels such as the aorta and pulmonary arteries remain open. When the DA fails to close after birth, the condition is known as patent DA, which is a common form of congenital heart defect. Patent DA is also a frequent problem with significant morbidity and mortality in premature infants. Investigating the molecular mechanism of DA closure is important not only for vascular biology but also for clinical problems in pediatrics. Voltage-dependent Ca 2ϩ channels (VDCCs) consist of multiple subtypes, named L-, N-, P/Q-, R-, and T-type. L-type VDCCs are known to play a primary role in regulating Ca 2ϩ influx and thus vascular tone in the development of arterial smooth muscle including the DA (2-4). Our previous study demonstrated that all T-type VDCCs were expressed in the rat DA (5). ␣1G subunit, especially, was the most dominant isoform among T-type VDCCs. The abundant expression of ␣1G subunit suggests that it plays a role in the vasoconstriction and vascular remodeling of the DA. In this regard, Nakanishi
Anesthesia & Analgesia, 2012
Ilioinguinal and iliohypogastric nerve blocks are used in the clinical management of persistent i... more Ilioinguinal and iliohypogastric nerve blocks are used in the clinical management of persistent inguinal postherniorrhaphy pain, but no controlled studies have been published on the subject. In this controlled study, we investigated the analgesic and sensory effects of ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerves with lidocaine. A randomized, double-blind, placebo-controlled, crossover trial in 12 patients with severe persistent inguinal postherniorrhaphy pain, including a control group of 12 healthy controls, was performed. Assessments included pain ratings under standardized conditions with numerical rating scale (0-10), sensory mapping to a cool roller, and quantitative sensory testing (QST), in the groin regions, before and after each ultrasound-guided block. A needle approach of 1 to 2 cm superior and medial to the anterior superior iliac spine was used. Outcomes were changes in pain ratings, sensory mapping, and QST compared with preblock values. Lidocaine responders were a priori defined by a pain reduction of ≥80% after lidocaine block and ≤25% after placebo block, nonresponders by pain reduction of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;80% after lidocaine block and ≤25% after placebo block, and placebo responders by pain reduction of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;25% after placebo block. One of 12 pain patients was a lidocaine responder, 6 patients were nonresponders, and 5 patients were placebo responders. No consistent QST changes were observed in patients after the lidocaine block. In 10 of 12 healthy controls, a cool hypoesthesia area developed in the groin after the lidocaine block. Furthermore, QST assessments demonstrated significantly decreased suprathreshold heat pain perception in the groin after lidocaine versus placebo blocks (95% confidence interval = -3.5 to -0.5, P = 0.008). Ultrasound-guided lidocaine blocks of the ilioinguinal and iliohypogastric nerves, at the level of the anterior superior iliac spine, are not useful in diagnosis and management of persistent inguinal postherniorrhaphy pain.
Biochemical and Biophysical Research Communications, 2014
PLOS ONE
Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to inc... more Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to increased expression of Na+-K+-2Cl-co-transporter isoform 1 (NKCC1), and the transition of GABAergic signaling from excitatory to inhibitory occurs before birth in the rat spinal cord and spreads rostrally according to the developmental changes in cationchloride co-transporter expression. We previously showed that midazolam activates the hippocampal CA3 area and induces less sedation in neonatal rats compared with adolescent rats in an NKCC1-dependent manner. In the present study, we tested the hypothesis that propofol-induced loss of righting reflex (LORR) but not immobilizing actions are modulated by NKCC1-dependent mechanisms and reduced in neonatal rats compared with adolescent rats. We estimated neuronal activity in the cortex, hippocampus and thalamus after propofol administration with or without bumetanide, an NKCC1 inhibitor, by immunostaining of phosphorylated cyclic adenosine monophosphate-response element binding protein (pCREB). We studied effects of bumetanide on propofol-induced LORR and immobilizing actions in postnatal day 7 and 28 (P7 and P28) rats. The pCREB expression in the cortex (P = 0.001) and hippocampus (P = 0.01) was significantly greater in the rats receiving propofol only than in the rats receiving propofol plus bumetanide at P 7. Propofol-induced LORR or immobilizing effects did not differ significantly between P7 and P28. Bumetanide significantly enhanced propofol-induced LORR (P = 0.031) but not immobilization in P7 rats. These results are partially consistent with our hypothesis. They suggest that propofol may activate the rostral but not caudal central nervous system dependently on NKCC1, and these differential actions may underlie the different properties of sedative and immobilizing actions observed in neonatal rats.
Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lyi... more Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 um in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons ...
Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lyi... more Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 um in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons ...
Pfl�gers Archiv European Journal of Physiology, 1998
The authors studied effects of opioid receptor agonists on neuronal nicotinic-receptor-mediated c... more The authors studied effects of opioid receptor agonists on neuronal nicotinic-receptor-mediated current in PC12 cells using whole-cell current recording. At 1 µM, [D-Ala, N-Me, Phe, Gly-ol]-enkephalin (DAMGO), a selective µ receptor agonist, or 10 µM methionine-enkephalin, a µ and δ receptor agonist, did not inhibit the current elicited by 30 µM nicotine significantly. Dynorphin A (1-17) (0.1-1 µM), an endogenous κ receptor agonist, and U50488 (0.1-10 µM), a non-peptide selective κ receptor agonist, depressed the nicotine-induced current reversibly in a dose-dependent manner. They accelerated the current decay, resulting in greater effects on the nondesensitized current than the peak current. These effects were not affected by nor-binaltrophimine, a selective κ receptor antagonist, or by inclusion of guanosine 5′-O-(2-thiobiphosphate) (GDP[β-S]), a GTP binding protein blocker, into the pipette solution. These results demonstrate that two κ opioid receptor agonists, dynorphin A (1-17) and U50488, inhibit neuronal nicotinic-receptormediated current without the involvement of opioid receptors or GTP binding proteins. The acceleration of the current decay suggests a direct action on nicotinic receptors such as open channel block, or augmentation of desensitization. Modulation of neuronal nicotinic receptors by dynorphins may play a role in some areas where dynorphin release sites and neuronal nicotinic receptors are colocalized.
European Journal of Anaesthesiology, 2005
0.5 mM and more, the phase transition temperature decreased to 40°C and below, which meant the lo... more 0.5 mM and more, the phase transition temperature decreased to 40°C and below, which meant the lowering of the membrane viscosity. Conclusion(s): In the clinical concentration of sevo and iso, viscosity of the phospholipid membrane was not almost changed. This result may support the recent findings that phospholipid membrane is not the major action site by volatile anesthetics.
PLOS ONE, 2021
Yokukansan (YKS) is a traditional Japanese herbal (Kampo) medicine prescribed for anxiety. In thi... more Yokukansan (YKS) is a traditional Japanese herbal (Kampo) medicine prescribed for anxiety. In this randomized controlled trial, we compared the subjective assessment of anxiety using questionnaires and its objective assessment using salivary alpha-amylase concentrations in YKS and control (CNT) groups of women undergoing breast surgery. The trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000028998), and the investigators were blinded to drug administration. One hundred patients who underwent breast cancer surgery were allocated to either the YKS or the CNT group. Finally, 35 and 42 patients in the YKS and CNT groups were analyzed, respectively. The YKS group received two 2.5 g doses of the medication before sleeping on the night before surgery and 2 h before inducing anesthesia, while the CNT group did not receive medication preoperatively. Patients answered two questionnaires, the Hospital Anxiety and De...
Brain research, Mar 1, 2018
We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord ... more We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as eviden...
JA Clinical Reports, 2017
Background: A scalp block or wound infiltration of local anesthetic is thought to effectively con... more Background: A scalp block or wound infiltration of local anesthetic is thought to effectively control post-craniotomy pain. However, it can result in local anesthetic toxicity (LAST), which is difficult to distinguish from brain damage due to the surgical procedure when emergence from general anesthesia is delayed. Lipid rescue (infusion of a lipid emulsion) is a widely accepted treatment for LAST. Case presentation: A 64-year-old man underwent surgical resection of a glioma in the brainstem. While still under general anesthesia, and before suturing of the wound, he received a 20-mL scalp infusion of ropivacaine 0.75%. His emergence from anesthesia was delayed, his respiration was suppressed, and premature ventricular contractions occurred; all of which are symptoms of LAST. Injection of a 20% lipid emulsion rapidly alleviated these symptoms. Interestingly, the blood concentration of ropivacaine increased after lipid rescue. Conclusions: The increase in ropivacaine concentration in the blood after lipid rescue suggests that the intravenously administered lipid emulsion absorbed the ropivacaine from the intoxicated brain and heart tissue. This finding is consistent with the lipid sink theory as a mechanistic explanation of lipid rescue.
JA Clinical Reports, 2015
Background: Acute postoperative pain is an integral risk factor in the development of chronic pai... more Background: Acute postoperative pain is an integral risk factor in the development of chronic pain after breast cancer surgery (BCS). Pectoral nerve block (PECSB) has been recently reported as an analgesic method for BCS. Here, we retrospectively compared intraoperative opioid requirement, postoperative pain after BCS, and incidence of postoperative nausea and vomiting (PONV) in patients who underwent BCS under total intravenous anesthesia (TIVA) with or without PECSB. Findings: We reviewed anesthesia charts and medical records of 146 patients who underwent BCS at Niigata University Medical and Dental Hospital from January 2013 to March 2014; 36 patients were included in the TIVA group, and 35 patients were included in the TIVA + PECSB group. Intraoperative remifentanil requirements were significantly lower in the TIVA + PECSB group than in the TIVA group, and the cumulative distribution of remifentanil was reduced in patients who received PECSB (TIVA: 10.9 ± 2.9 μg/kg/h; TIVA + PECSB: 7.3 ± 3.3 μg/kg/h; p < 0.001). Postoperative pain scores during the 48 h after surgery were significantly lower in the TIVA + PECSB group than in the TIVA group (TIVA: 2 [1-5]; TIVA + PECSB: 1 [0-5]; p = 0.03). However, administration of fentanyl during operation, percentage of patients requiring supplemental analgesics, and incidence of PONV were not significantly different between groups. Conclusions: PECSB significantly reduced intraoperative remifentanil usage and postoperative pain. However, the requirement for postoperative supplemental analgesics and the incidence of PONV did not differ. These data suggested that PECSB may be useful for perioperative pain management in patients undergoing BCS.
JA Clinical Reports, 2015
Background: Analgesia after Cesarean delivery (CD) requires early ambulation to prevent thromboem... more Background: Analgesia after Cesarean delivery (CD) requires early ambulation to prevent thromboembolic disease and to facilitate baby care. We retrospectively reviewed anesthesia charts and medical records of patients who underwent CD to compare the efficacy of spinal anesthesia supplemented with intrathecal morphine hydrochloride (ITM) and combined spinal-epidural anesthesia followed by opioid-free epidural analgesia (CSEA-EDA). Findings: All subjects underwent CD at Nagaoka Chuo General Hospital between February 2012 and January 2013. Patient characteristics, time to first analgesic rescue after CD, and analgesic use after CD were examined. Incidences of postural hypotension, lower extremity numbness/weakness, postoperative nausea/vomiting (PONV), and pruritus were also examined for 48 h after CD. Average time to first analgesic use after CD (ITM 25.13 ± 16.07 h, CSEA-EDA 22.42 ± 16.27 h, p = 0.521) and cumulative probability of rescue analgesic use (p = 0.139 by log-rank test) were comparable between groups. However, average analgesic use within 24 h was lower in the ITM group (0.75 ± 1.05 times) than in the CSEA-EDA group (1.52 ± 1.72 times, p = 0.0497). Numbness or motor weakness in lower extremities only occurred in the CSEA-EDA group, and pruritus only occurred in the ITM group. Conclusions: The results of this study suggest that ITM is better than CSEA-EDA for anesthesia following CD with regard to pain control. Also, ITM would be advantageous for early ambulation following CD because of lower incidence of numbness and motor weakness in lower extremities compared to CSEA-EDA.
JA Clinical Reports, 2015
Background: Analgesia after Cesarean delivery (CD) requires early ambulation to prevent thromboem... more Background: Analgesia after Cesarean delivery (CD) requires early ambulation to prevent thromboembolic disease and to facilitate baby care. We retrospectively reviewed anesthesia charts and medical records of patients who underwent CD to compare the efficacy of spinal anesthesia supplemented with intrathecal morphine hydrochloride (ITM) and combined spinal-epidural anesthesia followed by opioid-free epidural analgesia (CSEA-EDA). Findings: All subjects underwent CD at Nagaoka Chuo General Hospital between February 2012 and January 2013. Patient characteristics, time to first analgesic rescue after CD, and analgesic use after CD were examined. Incidences of postural hypotension, lower extremity numbness/weakness, postoperative nausea/vomiting (PONV), and pruritus were also examined for 48 h after CD. Average time to first analgesic use after CD (ITM 25.13 ± 16.07 h, CSEA-EDA 22.42 ± 16.27 h, p = 0.521) and cumulative probability of rescue analgesic use (p = 0.139 by log-rank test) were comparable between groups. However, average analgesic use within 24 h was lower in the ITM group (0.75 ± 1.05 times) than in the CSEA-EDA group (1.52 ± 1.72 times, p = 0.0497). Numbness or motor weakness in lower extremities only occurred in the CSEA-EDA group, and pruritus only occurred in the ITM group. Conclusions: The results of this study suggest that ITM is better than CSEA-EDA for anesthesia following CD with regard to pain control. Also, ITM would be advantageous for early ambulation following CD because of lower incidence of numbness and motor weakness in lower extremities compared to CSEA-EDA.
Journal of Pharmacological Sciences, 2010
Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite ... more Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for axonal transport has been lacking. In order to better characterize the molecular mechanisms involved in axonal transport, we here developed a computer-assisted monitoring system. Using lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine (CM-DiI) as a labeling dye, we have successfully labeled membranous organelles in cultured chick dorsal root ganglia neurons. We confirmed that sodium azide, an ATPase inhibitor, and nocodazole, a microtubule-destabilizing agent, markedly suppressed anterograde and retrograde axonal transport of CM-DiI-labeled particles. We further tested the effects of several anti-neoplastic drugs on axonal transport. Paclitaxel, vincristine, cisplatin, and oxaliplatin, all of which are known to be neurotoxic and to cause neurological symptoms, suppressed anterograde and retrograde axonal transport. Another series of anti-neoplastic drugs, including methotrexate and 5-fluorouracil, did not affect the axonal transport. This is the first report of an automated monitoring system for axonal transport. This system will be useful for toxicity assays, characterizing axonal transport, or screening drugs that may modify neuronal functions.
The Journal of Emergency Medicine, 2013
Background: Therapeutic hypothermia (TH) is one of the key treatments after cardiac arrest (CA). ... more Background: Therapeutic hypothermia (TH) is one of the key treatments after cardiac arrest (CA). Selection of post-CA patients for TH remains problematic, as there are no clinically validated tools to determine who might benefit from the therapy. Objective: The aim of this study was to investigate retrospectively whether laboratory findings or other patient data obtained during the early phase of hospital admission could be correlated with neurological outcome after TH in comatose survivors of CA. Methods: Medical charts of witnessed CA patients admitted between June 2003 and July 2009 who were treated with TH were reviewed retrospectively. The subjects were grouped based on their cerebral performance category (CPC) 6 months after CA, as either good recovery (GR) for CPC 1-2 or non-good recovery (non-GR) for CPC 3-5. The following well-known determinants of outcome obtained during the early phase of hospital admission were evaluated: age, gender, body mass index, cardiac origin, presence of ventricular fibrillation (VF), time from collapse to cardiopulmonary resuscitation, time from collapse to return of spontaneous circulation, body temperature, arterial blood gases, and blood test results. Results: We analyzed a total of 50 (25 GR and 25 non-GR) patients. Multivariate logistic analysis showed that initial heart rhythm and pH levels were significantly higher in the GR group than in the non-GR group (ventricular tachycardia/VF rate: p = 0.055, 95% confidence interval [CI] 0.768-84.272, odds ratio [OR] 8.047; pH: 7.155 ± 0.139 vs. 6.895 ± 0.100, respectively, p < 0.001, 95% CI 1.838-25.827; OR 6.89). Conclusion: These results imply that in addition to initial heart rhythm, pH level may be a good candidate for neurological outcome predictor even though previous research has found no correlation between initial pH value and neurological outcome. Crown
Journal of Biological Chemistry, 2005
Journal of Biological Chemistry, 2009
The ductus arteriosus (DA), an essential vascular shunt for fetal circulation, begins to close im... more The ductus arteriosus (DA), an essential vascular shunt for fetal circulation, begins to close immediately after birth. Although Ca 2؉ influx through several membrane Ca 2؉ channels is known to regulate vasoconstriction of the DA, the role of the T-type voltage-dependent Ca 2؉ channel (VDCC) in DA closure remains unclear. Here we found that the expression of ␣1G, a T-type isoform that is known to exhibit a tissue-restricted expression pattern in the rat neonatal DA, was significantly upregulated in oxygenated rat DA tissues and smooth muscle cells (SMCs). Immunohistological analysis revealed that ␣1G was localized predominantly in the central core of neonatal DA at birth. DA SMC migration was significantly increased by ␣1G overexpression. Moreover, it was decreased by adding ␣1G-specific small interfering RNAs or using R(؊)-efonidipine, a highly selective T-type VDCC blocker. Furthermore, an oxygenationmediated increase in an intracellular Ca 2؉ concentration of DA SMCs was significantly decreased by adding ␣1G-specific siRNAs or using R(؊)-efonidipine. Although a prostaglandin E receptor EP4 agonist potently promoted intimal thickening of the DA explants, R(؊)-efonidipine (10 ؊6 M) significantly inhibited EP4-promoted intimal thickening by 40% using DA tissues at preterm in organ culture. Moreover, R(؊)-efonidipine (10 ؊6 M) significantly attenuated oxygenation-induced vasoconstriction by ϳ27% using a vascular ring of fetal DA at term. Finally, R(؊)-efonidipine significantly delayed the closure of in vivo DA in neonatal rats. These results indicate that T-type VDCC, especially ␣1G, which is predominantly expressed in neonatal DA, plays a unique role in DA closure, implying that T-type VDCC is an alternative therapeutic target to regulate the patency of DA. The ductus arteriosus (DA) 2 is an essential vascular shunt between the aortic arch and the pulmonary trunk during a fetal period (1). After birth, the DA closes immediately in accordance with its smooth muscle contraction and vascular remodeling, whereas the connecting vessels such as the aorta and pulmonary arteries remain open. When the DA fails to close after birth, the condition is known as patent DA, which is a common form of congenital heart defect. Patent DA is also a frequent problem with significant morbidity and mortality in premature infants. Investigating the molecular mechanism of DA closure is important not only for vascular biology but also for clinical problems in pediatrics. Voltage-dependent Ca 2ϩ channels (VDCCs) consist of multiple subtypes, named L-, N-, P/Q-, R-, and T-type. L-type VDCCs are known to play a primary role in regulating Ca 2ϩ influx and thus vascular tone in the development of arterial smooth muscle including the DA (2-4). Our previous study demonstrated that all T-type VDCCs were expressed in the rat DA (5). ␣1G subunit, especially, was the most dominant isoform among T-type VDCCs. The abundant expression of ␣1G subunit suggests that it plays a role in the vasoconstriction and vascular remodeling of the DA. In this regard, Nakanishi
Anesthesia & Analgesia, 2012
Ilioinguinal and iliohypogastric nerve blocks are used in the clinical management of persistent i... more Ilioinguinal and iliohypogastric nerve blocks are used in the clinical management of persistent inguinal postherniorrhaphy pain, but no controlled studies have been published on the subject. In this controlled study, we investigated the analgesic and sensory effects of ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerves with lidocaine. A randomized, double-blind, placebo-controlled, crossover trial in 12 patients with severe persistent inguinal postherniorrhaphy pain, including a control group of 12 healthy controls, was performed. Assessments included pain ratings under standardized conditions with numerical rating scale (0-10), sensory mapping to a cool roller, and quantitative sensory testing (QST), in the groin regions, before and after each ultrasound-guided block. A needle approach of 1 to 2 cm superior and medial to the anterior superior iliac spine was used. Outcomes were changes in pain ratings, sensory mapping, and QST compared with preblock values. Lidocaine responders were a priori defined by a pain reduction of ≥80% after lidocaine block and ≤25% after placebo block, nonresponders by pain reduction of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;80% after lidocaine block and ≤25% after placebo block, and placebo responders by pain reduction of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;25% after placebo block. One of 12 pain patients was a lidocaine responder, 6 patients were nonresponders, and 5 patients were placebo responders. No consistent QST changes were observed in patients after the lidocaine block. In 10 of 12 healthy controls, a cool hypoesthesia area developed in the groin after the lidocaine block. Furthermore, QST assessments demonstrated significantly decreased suprathreshold heat pain perception in the groin after lidocaine versus placebo blocks (95% confidence interval = -3.5 to -0.5, P = 0.008). Ultrasound-guided lidocaine blocks of the ilioinguinal and iliohypogastric nerves, at the level of the anterior superior iliac spine, are not useful in diagnosis and management of persistent inguinal postherniorrhaphy pain.
Biochemical and Biophysical Research Communications, 2014
PLOS ONE
Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to inc... more Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to increased expression of Na+-K+-2Cl-co-transporter isoform 1 (NKCC1), and the transition of GABAergic signaling from excitatory to inhibitory occurs before birth in the rat spinal cord and spreads rostrally according to the developmental changes in cationchloride co-transporter expression. We previously showed that midazolam activates the hippocampal CA3 area and induces less sedation in neonatal rats compared with adolescent rats in an NKCC1-dependent manner. In the present study, we tested the hypothesis that propofol-induced loss of righting reflex (LORR) but not immobilizing actions are modulated by NKCC1-dependent mechanisms and reduced in neonatal rats compared with adolescent rats. We estimated neuronal activity in the cortex, hippocampus and thalamus after propofol administration with or without bumetanide, an NKCC1 inhibitor, by immunostaining of phosphorylated cyclic adenosine monophosphate-response element binding protein (pCREB). We studied effects of bumetanide on propofol-induced LORR and immobilizing actions in postnatal day 7 and 28 (P7 and P28) rats. The pCREB expression in the cortex (P = 0.001) and hippocampus (P = 0.01) was significantly greater in the rats receiving propofol only than in the rats receiving propofol plus bumetanide at P 7. Propofol-induced LORR or immobilizing effects did not differ significantly between P7 and P28. Bumetanide significantly enhanced propofol-induced LORR (P = 0.031) but not immobilization in P7 rats. These results are partially consistent with our hypothesis. They suggest that propofol may activate the rostral but not caudal central nervous system dependently on NKCC1, and these differential actions may underlie the different properties of sedative and immobilizing actions observed in neonatal rats.