Yasunori Matsunari

ADAMTS13 safeguards the myocardium in a mouse model of acute myocardial infarction

Masaaki Doi1,2; Hideto Matsui1; Yukiji Takeda3; Yoshihiko Saito3; Maiko Takeda4; Yasunori Matsunari1,5; Kenji Nishio6; Midori Shima2; Fumiaki Banno7; Masashi Akiyama7; Koichi Kokame7; Toshiyuki Miyata7; Mitsuhiko Sugimoto1 1Department of Regulatory Medicine for Thrombosis, Nara Medical University, Kashihara, Japan; 2Department of Pediatrics, Nara Medical University, Kashihara, Japan; 3Department of Internal Medicine, Nara Medical University, Kashihara, Japan; 4Department of Pathology, Nara Medical University, Kashihara, Japan; 5Department of Anesthesiology, Nara Medical University, Kashihara, Japan; 6Department of General Medicine, Nara Medical University, Kashihara, Japan; 7Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka, Japan

Evaluation of the effects of α-phenyl-N-tert-butyl nitrone pretreatment on the neurobehavioral effects of methamphetamine

A relationship between formation of reactive oxygen species (ROS) and energy depletion has been proposed to play an important role in mediating methamphetamine (METH)-induced neurotoxicity. To evaluate this relationship, we examined the effect of the spin-trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN) on hyperthermia and self-injurious behavior (SIB) and striatal dopamine (DA) depletion produced by METH (4 injections of 4 mg/kg, 2 hr intervals, s.c.) in BALB/c mice. Repeated administration of METH induced hyperthermia, incidence of SIB and striatal DA depletion (84% after 3 days). Pretreatment with PBN (4 injections of 60 or 120 mg/kg, i.p.) reduced METH-induced hyperthermia, but did not significantly attenuate METH-induced SIB or the striatal DA depletion. On the other hand, pretreatment with high doses of PBN (4 injections of 180 or 240 mg/kg, i.p.) protected against METH-induced hyperthermia and SIB, and PBN (180 mg/kg) also completely protected against the acute striatal DA depletion 60 min after the last injection of the drug. However, the long-lasting striatal DA depletion was only attenuated by 52 or 56%, respectively. These results indicate that METH-induced hyperthermia contributes to, but is not solely responsible for METH-induced neurotoxicity, and supports a role for formation of ROS and other mechanisms in the generation of METH-induced striatal dopaminergic neurotoxicity. In addition, the difference in the efficacy of PBN to protect against the acute or long-lasting striatal DA depletion induced by METH may indicate that both ROS formation and other mechanisms are required for METH-induced neurotoxicity to develop.

Relevant role of von Willebrand factor in neutrophil recruitment in a mouse sepsis model involving cecal ligation and puncture.

Sepsis is a systemic inflammatory response syndrome caused by severe microbial infection. Uncontrollable activation of both inflammatory and coagulation pathways may result in multiple organ failure, a leading cause of death in intensive care units even in developed countries. An adhesive protein,

Coagulation potential of immobilised factor VIII in flow-dependent fibrin generation on platelet surfaces

Coagulation factor VIII (FVIII) plays an essential role in haemostasis. To date, physiologic activity of FVIII circulating in the bloodstream (S-FVIII) is evaluated by classic coagulation assays. However, the functional relevance of FVIII (-von Willebrand factor complex) immobilised on thrombogenic surfaces (I-FVIII) remains unclear. We used an in vitro perfusion chamber system to evaluate the function of I-FVIII in the process of mural thrombus formation under whole blood flow conditions. In perfusion of either control or synthetic haemophilic blood, the intra-thrombus fibrin generation on platelet surfaces significantly increased as a function of I-FVIII, independent of S-FVIII, under high shear rate conditions. This I-FVIII effect was unvarying regardless of anti-FVIII inhibitor levels in synthetic haemophilic blood. Thus, our results illustrate coagulation potentials of immobilised clotting factors, distinct from those in the bloodstream, under physiologic flow conditions and may give a clue for novel therapeutic approaches for haemophilic patients with anti-FVIII inhibitors.

Contribution of ADAMTS13 to the better cell engraftment efficacy in mouse model of bone marrow transplantation

The adhesive protein von Willebrand factor (VWF) plays an essential role in physiological hemostasis, mediating platelet adhesion and aggregation under high shear stress conditions.[1][1],[2][2] The VWF-cleaving protease ADAMTS13 precisely down-regulates VWF activity to avoid pathological

Fat embolism syndrome in a child triggered by surgical tourniquet release: A case report

1. Lonnqvist PA, Habre W. Midazolam as premedication: is the emperor naked or just half-dressed? Pediatr Anesth. 2005;15:263-265. 2. Kanegaye JT, Favela JL, Acosta M, Bank DE. High-dose rectal midazolam for pediatric procedures: a randomized trial of sedative efficacy and agitation. Pediatr Emerg Care. 2003;19:329-336. 3. McGraw T, Kendrick A. Oral midazolam premedication and postoperative behaviour in children. Paediatr Anaesth. 1998;8: 117-121. 4. Lu C, Zhang LM, Zhang Y, et al. Intranasal dexmedetomidine as a sedative premedication for patients undergoing suspension laryngoscopy: a randomized double-blind study. PLoS ONE. 2016;11: e0154192. 5. Peng K, Wu SR, Ji FH, Li J. Premedication with dexmedetomidine in pediatric patients: a systematic review and meta-analysis. Clinics. 2014;69:777-786.

Functional characterization of tissue factor in von Willebrand factor-dependent thrombus formation under whole blood flow conditions

Von Willebrand factor (VWF) plays an important role in mediating platelet adhesion and aggregation under high shear rate conditions. Such platelet aggregates are strengthened by fibrin-network formation triggered by tissue factor (TF). However, little is known about the role of TF in VWF-dependent thrombus formation under blood flow conditions. We evaluated TF in thrombus formation on immobilized VWF under whole blood flow conditions in an in vitro perfusion chamber system. Surface-immobilized TF amplified intra-thrombus fibrin generation significantly under both low and high shear flow conditions, while TF in sample blood showed no appreciable effects. Furthermore, immobilized TF enhanced VWF-dependent platelet adhesion and aggregation significantly under high shear rates. Neutrophil cathepsin G and elastase increased significantly intra-thrombus fibrin deposition on immobilized VWF–TF complex, suggesting the involvement of leukocyte inflammatory responses in VWF/TF-dependent mural thrombogenesis under these flow conditions. These results reveal a functional link between VWF and TF under whole blood flow conditions, in which surface-immobilized TF and VWF mutually contribute to mural thrombus formation, which is essential for normal hemostasis. By contrast, TF circulating in blood may be involved in systemic hypercoagulability, as seen in sepsis caused by severe microbial infection, in which neutrophil inflammatory responses may be active.