1995 Fiscal Year Final Research Report Summary
New devices in anticoagulant therapy for massive hepatic necrosis through sinusoidal fibrin deposition
| Project/Area Number |
06454258
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Saitama Medical School |
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Principal Investigator |
FUJIWARA Kenji Saitama Medical School, Faculty of Medicine, Professor, 医学部, 教授 (80101088)
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| Co-Investigator(Kenkyū-buntansha) |
MOCHIDA Satoshi Saitama Medical School, Faculty of Medicine, Assistant Professor, 医学部, 講師 (20219968)
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| Project Period (FY) |
1994 – 1995
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| Keywords | fulminant hepatitie / acute liver failure / sinusoidal fibrin doposition / Kupffer cells / sinusoidal endothetial cells |
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| Research Abstract |
Massive hepatic necrosis, characteristic of fulminant viral hepatitis, occurs as a result of microcirculatory disturbance due to deranged blood coagulation equilibrium between Kupffer cells and sinusoidal endothelial cells. Anticoagulant activity in the hepatic sinusoids was decreased compared to the vessels in other organs as a consequence of no or extremely reduced expressionof tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) on endothelial cells. Thus, the replacement of TFPI and TM might be a powerful therapy for such liver injury. When rats received recombinant human TFPI intravenously, TFPI disappeared from the circulation rapidly after the injection, and were detected on the surface of sinusoidal endothelial cells and microvilli of hepatocytes, suggesting that TFPI may act as an anticoagulant exclusively on the sinusoidal walls. TM was designed to exert its action enhanced on sinusoidal endothelial cells by expression as a targeting gene through mannose receptors. Intraportal injection of miscells containing mannose and FITC on the surface produced fluorescence products on the lining of sinusoidal walls. These anticoagulant devices targeting hepatic sinusoidal walls may be therapeutic candidates for fulminant viral hepatitis with minimal adverse effects of general bleeding.
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[Publications] Fujiwara K,Mochida S,Ohno A,Arai M,Matsui A,Masaki N,Hirata K,Tomiya T,Yamaoka M,Nagoshi S,Ohta Y,Ogata I,Francavilla A,Van Thiel DH,Starzel TE.: "Use of Prostaglandin I_2 Analog in Treatment of Massive Hepatic Necrosis Associated with Endothelial Cell Injury and Diffuse Sinusoidal Fibrin Deposition." Dig Dis Sci. 40. 41-47 (1995)
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「研究成果報告書概要(欧文)」より
