1,218 research outputs found

    Supplemental material for The randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion (SKIP study)

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    Supplemental Material for The randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion (SKIP study) by Kentaro Suzuki, Kazumi Kimura, Masataka Takeuchi, Masafumi Morimoto, Ryuzaburo Kanazawa, Yuki Kamiya, Keigo Shigeta, Norihiro Ishii, Yohei Takayama, Yorio Koguchi, Tomoji Takigawa, Mikito Hayakawa, Takahiro Ota, Seiji Okubo, Hiromichi Naito, Kazunori Akaji, Noriyuki Kato, Masato Inoue, Teruyuki Hirano, Kazunori Miki, Toshihiro Ueda, Yasuyuki Iguchi, Shigeru Fujimoto, Toshiaki Otsuka and Yuji Matsumaru in International Journal of Stroke</p

    Role of Calcium Conductances on Spike Afterpotentials in Rat Trigeminal Motoneurons

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    Kobayashi, Masayuki, Tomio Inoue, Ryuji Matsuo, Yuji Masuda, Osamu Hidaka, Youngnam Kang, and Toshifumi Morimoto. Role of calcium conductances on spike afterpotentials in rat trigeminal motoneurons. J. Neurophysiol. 77: 3273–3283, 1997. Intracellular recordings were obtained from rat trigeminal motoneurons in slice preparations to investigate the role of calcium conductances in the depolarizing and hyperpolarizing spike afterpotential (ADP and mAHP, respectively). The mAHP was suppressed by bath application of 1 μM apamin, 2 mM Mn2+, and 2 mM Co2+, and also by intracellular injection of ethylene glycol-bis(b-aminoethylenether)- N,N,N′,N′-tetraacetic acid (EGTA), suggesting that the potassium conductance generating the mAHP is activated by Ca2+ influx. Mn2+ (2 mM) or Cd2+ (500 μM) reduced the ADP, whereas the ADP amplitude was increased by raising extracellular Ca2+ concentration from 2 to 8 mM by bath application of Ba2+ (0.5–5 mM) and by intracellular injection of EGTA. This would suggest that Ca2+ itself is likely to be the charge carrier generating the ADP. Focal application of ω-conotoxin GVIA (10–30 μM) suppressed the mAHP and enhanced the ADP, whereas focal application of ω-agatoxin IVA (10–100 μM) reduced the ADP amplitude without apparent effects on the mAHP. We conclude that Ca2+ influx through ω-agatoxin IVA–sensitive calcium channels is at least in part responsible for the generation of the ADP and that Ca2+ influx through ω-conotoxin GVIA–sensitive calcium channels contributes to the generation of the mAHP. Because of the selective suppression of the ADP and mAHP by ω-agatoxin IVA and ω-conotoxin GVIA, respectively, it is suggested that both calcium channels are separated geometrically in rat trigeminal motoneurons. </jats:p

    Chronological changes in plasma levobupivacaine concentrations after bilateral modified thoracoabdominal nerve block through perichondrial approach

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    The local anesthetic (LA) systemic toxicity of trunk blocks is a major concern. Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has attracted attention; however, plasma LA level is unknown. We tested whether the peak plasma LA concentration following M-TAPA, using 25 mL of 0.25% levobupivacaine mixed with epinephrine on each side, would be below the toxic level (2.6 mu g/mL). We recruited 10 patients undergoing abdominal surgery with planned M-TAPA between November 2021 and February 2022. In all patients, 25 mL of 0.25% levobupivacaine mixed with 1:200,000 epinephrine was administered on each side. Blood samples were obtained at 10, 20, 30, 45, 60, and 120 min after the block. The highest individual peak and the mean peak plasma LA concentrations were 1.03 and 0.73 mu g/mL, respectively. We could not capture the peak in five patients; however, the highest concentrations in all patients were significantly lower than the toxic level. A negative correlation between the peak level and body weight was observed. Our results indicated that the plasma LA concentration following M-TAPA using total of 50 mL of 0.25% levobupivacaine with epinephrine remains below the toxic level. Further research is required due to the small sample size of this study.Trial registry number: UMIN000045406

    MINO prevents LTP impairment during sepsis

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    Sepsis-associated encephalopathy is a major complication during sepsis, and an effective treatment remains unknown. Although minocycline (MINO) has neuroprotective effects and is an attractive candidate for treating sepsis-associated encephalopathy, the effect of MINO on synaptic plasticity during sepsis is still unclear. In the present study, we investigated the effects of MINO on long-term potentiation (LTP) in the hippocampus in a cecal ligation and puncture (CLP) mouse model. We divided mice into four groups; sham + vehicle, sham + MINO (60 mg/kg, i.p. for 3 consecutive days before slice preparation), CLP + vehicle, and CLP + MINO. We tested LTP in the CA1 region of the hippocampus, using slices taken 24 h after surgery. Because MINO is also anti-inflammatory, LTP was analyzed following 30 min of IL-1 receptor antagonist (IL-1ra) perfusion. The endotoxin level in the blood was increased at 24 h after CLP operations regardless of MINO administrations, and LTP in the CLP + vehicle group mice was severely impaired (P < 0.05). High doses of MINO prevented the LTP impairment during sepsis in the CLP + MINO group. Interleukin (IL)-1ra administration ameliorated LTP impairment only in the CLP + vehicle group (P < 0.05); it had no additional effects on LTP in the CLP + MINO group. In conclusion, we have provided the first evidence that MINO prevents impaired LTP related to sepsis-induced encephalopathy in the mouse hippocampus, and that mechanisms associated with IL-1 receptor activity may be involved

    Author response image 1.

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    Neurotransmitter is released at synapses by fusion of synaptic vesicles with the plasma membrane. To sustain synaptic transmission, compensatory retrieval of membranes and vesicular proteins is essential. We combined capacitance measurements and pH-imaging via pH-sensitive vesicular protein marker (anti-synaptotagmin2-cypHer5E), and compared the retrieval kinetics of membranes and vesicular proteins at the calyx of Held synapse. Membrane and Syt2 were retrieved with a similar time course when slow endocytosis was elicited. When fast endocytosis was elicited, Syt2 was still retrieved together with the membrane, but endocytosed organelle re-acidification was slowed down, which provides strong evidence for two distinct endocytotic pathways. Strikingly, CaM inhibitors or the inhibition of the Ca2+-calmodulin-Munc13-1 signaling pathway only impaired the uptake of Syt2 while leaving membrane retrieval intact, indicating different recycling mechanisms for membranes and vesicle proteins. Our data identify a novel mechanism of stimulus-and Ca2+-dependent regulation of coordinated endocytosis of synaptic membranes and vesicle proteins

    N=2 supersymmetric dynamics for pedestrians

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    Understanding the dynamics of gauge theories is crucial, given the fact that all known interactions are based on the principle of local gauge symmetry. Beyond the perturbative regime, however, this is a notoriously difficult problem. Requiring invariance under supersymmetry turns out to be a suitable tool for analyzing supersymmetric gauge theories over a larger region of the space of parameters. Supersymmetric quantum field theories in four dimensions with extended N=2 supersymmetry are further constrained and have therefore been a fertile field of research in theoretical physics for quite some time. Moreover, there are far-reaching mathematical ramifications that have led to a successful dialogue with differential and algebraic geometry. These lecture notes aim to introduce students of modern theoretical physics to the fascinating developments in the understanding of N=2 supersymmetric gauge theories in a coherent fashion. Starting with a gentle introduction to electric-magnetic duality, the author guides readers through the key milestones in the field, which include the work of Seiberg and Witten, Nekrasov, Gaiotto and many others. As an advanced graduate level text, it assumes that readers have a working knowledge of supersymmetry including the formalism of superfields, as well as of quantum field theory techniques such as regularization, renormalization and anomalies. After his graduation from the University of Tokyo, Yuji Tachikawa worked at the Institute for Advanced Study, Princeton and the Kavli Institute for Physics and Mathematics of the Universe. Presently at the Department of Physics, University of Tokyo, Tachikawa is the author of several important papers in supersymmetric quantum field theories and string theory
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