Project/Area Number |
13470324
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Anesthesiology/Resuscitation studies
|
Research Institution | Kagoshima University |
Principal Investigator |
MARUYAMA Ikuro Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (20082282)
|
Co-Investigator(Kenkyū-buntansha) |
YAMAKUCHI Munekazu Kagoshima University, Faculty of Medicine, Research Associate, 医学部, 助手 (20325814)
HASHIGUCHI Teruto Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70250917)
KANMURA Yuichi Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (30211189)
NAKAJIMA Toshihiro St. Marianna University, Department of Genome Science, Associate Professor, 難病治療研究センター, 助教授 (90260752)
IMAIZUMI Hitoshi Sapporo Medical University, Intensive Care Unit, Associate Professor, 集中治療部, 助教授 (70203304)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
|
Keywords | HMG-1 / anandamide / endocannabinoids / 2-arachidonylflyceorol / septic shock / polymyxin B / アナンダマイド / エンドトキシンショック / ポリミキシンB / アポトーシス |
Research Abstract |
Bacterial septicemia results hypotensive shock in severe cases. Various mediators have been proposed as causative factors in this hypotensive shock. These include inflammatory cytokines, PAF, NO and so on. However the inhibitors or antibodies against the mediators failed to improve hypotensive shock in clinical studies. Thus the other mediators may exist to cause septic shock. In the present investigations, we identified that endocannabinoids, anandamide and 2-arachidonylglycerol which axe produced and secreted from stimulated macrophages and platelets induce hypotension, and act as an early hypotensive mediators. We also identified that polymyxin B selectively binds these endocannabinoids. Hemo-perfusion through polymyxin B-coated biomembrane column efficiently removed the circulating endocannabinoids and results rapid improvement of the hypotension. Then we investigated the role of HMG-1 on the pathogenesis of septic shock, and showed that HMG-1 may act as a late phase mediator in septic shock.
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