Clinical and experimental study for regulation of apoptosis and necrosis in acute liver failure
| Project/Area Number |
10670497
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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 |
Gastroenterology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
SUZUKI Kazuyuki Faculty of Medicine, Iwate Medical University, Assistant Professor, 医学部, 助教授 (00137499)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO Ryujin Faculty of Medicine, Iwate Medical University, Assistant, 医学部, 助手 (70316355)
ABE Koichi Faculty of Medicine, Iwate Medical University, Assistant, 医学部, 助手 (90285586)
TAKIKAWA Yasuhiro Faculty of Medicine, Iwate Medical University, Assistant, 医学部, 助手 (50254751)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | acute liver failure / Fulminant hepatitis / liver necrosis / anootosis / Fas ligand / TNF receptor / glucocoryicoid / immunosuppressive drug / ネクローシス / サイトカイン |
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| Research Abstract |
(1) Clinical study: we measured the serum levels of soluble Fas, Fas ligand(FasL), tumor necrosis factor alfa (TNF α) and TNF receptor-1(TNFR1) in patients with acute hepatitis (AH) and fulminant hepatitis(FH). We also evaluated the relationship between these parameters and the prognosis of disease. The serum sFas and sFasL levels were significantly increased in patients with AH and FH compared to that in normal subjects. However, there were no differences between AH and FH. The serum TNF a and TNFR1 were also significantly increased in patients with AH and FH. In paticular, the serum TNFR1 levels were significantly increased in patients with FH compared to that of AH patients, and it reflected the severity of liver damage and the prognosis of hepatitis. Our data suggest that the Fas-FasL system and TNFα and TNFR1 are closely associated with the early process of massive hepatic necrosis.
(2) Experimental study: we evaluated whether the administration of glucocorticoid and cyclosporin A could protect acute liver injury induced by galactosamin and lipopolysaccharide in rats. The glucocorticoid inhibited both TNFα production and apoptosis, resulting in the protection of the development of massive liver necrosis. On the other hand, cyclospolin A was also protective against acute liver injury, if it is administered at an apopriate time during the course of liver injury. Although cyclosporin A did not inhibit both TNFα production and apoptosis, it inhibited the neutrophil infiltration into the liver tissue. Further studies are needed to clarify the mechanisms of the effect of these druges on acute liver injury model.
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Report
(3 results)
Research Products
(5 results)
