| Project/Area Number |
16591622
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Keio University |
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Principal Investigator |
NAKAGAWA Ken Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (50227740)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAJIMA Akira Keio University, School of Medicine, Instructor, 医学部, 助手 (90245572)
KOUNO Hidaka Keio University, School of Medicine, Instructor, 医学部, 助手 (50338133)
MURAI Masaru Keio University, School of Medicine, Professor, 医学部, 教授 (90101956)
篠島 利明 慶應義塾大学, 医学部, 助手 (60306777)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | DHMEQ / Transplantation / Ischemia-reperfusion injury / Acute rejection |
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| Research Abstract |
Ischemia-reperfusion (I/R) injury, acute refection and chronic rejection in kidney transplantation cause to the graft loss. NF-kB is a transcriptional factor of each adverse event. Therefore, an agent that blocks NF-kB may be a possibly new immunosuppressant. Using a new blocker to NF-kB, dehydroxymethylepoxyquinomicin (DHMEQ), a primary end point is to study the effects for each adverse events and a final end point is to study the possibility as a new immunosuppressant. At first, an in vitro study for ischemia-reperfusion injury was planed. HK2 cells were situated under the normoxia, hypoxia or H_2O_2 condition after the pre-conditioning with DHMEQ. The cells were evaluated with tripan blue dye exclusion and CDCFH assay. The viability was decreased in the concentration over 4μg/ml under normoxia, and over 16μg/ml under hypoxia. And the experimental concentration was determined at 8μg/ml from the results and the previous study for a urological cancer. The cells with the preconditioning with DHMEQ were damaged with the higher concentration of H_2O_2. The preconditioning of DHMEQ didn't affect to the ROS activity of HK2. But DHMEQ prevented completely the expression of ICAM-1 and the production of MCP-1 or IL-8. The preconditioning wasn't appropriate as the administration of DHMEQ and an intra-peritoneal administration was employed for in vivo studies. In a rat I/R injury model, a single DHMEQ (8mg/kg) administration before I/R, a 7 days DHMEQ administration after I/R and no DHMEQ were studied. The single administration before I/R kept the enough urine volume and the normal s-Cr level comparing with other 2 groups. Also, DHMEQ prevented the acute rejection in a rat skin graft model.
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