| Project/Area Number |
01570751
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Yamanashi Medical' College |
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Principal Investigator |
YAMAMOTO Masayuki Yamanashi Medical College, Surgery, Assistant Professor, 医学部, 講師 (30158307)
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| Co-Investigator(Kenkyū-buntansha) |
IIZUK Hidehiko Yamanashi Medical College, Surgery Assistant, 医学部, 助手 (60184347)
AOYAMA Hidehisa Yamanashi Medical College, Surgery Assistant, 医学部, 助手 (60159308)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1990: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Postoperative liver failure / Liver death / Arterial ketone body ratio / Severe infection / Energy Charge / TNF / Kupfer cells / Alueolar endothelial cell / 多臓器不全 / 肝不全 / 消化管出血 / 肝エネルギ-レベル / 細菌貧食能 |
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| Research Abstract |
Primary factors inducing the postoperative liver failure are disturbance of the host defence mechanism and existence of persistent infection. Through the research period, it has been investigated clinically and experimentally how the liver plays a role to maintain interrelationships between other organs as a center of the metabolic as well as reticuloendothelial systems. Since the reversibility of the liver function depends on that of mitochondrial function, we have analyzed clinical status proceeding to liver failure by using the arterial ketone body ratio, the ratio of acetoacetate to 3-hydroxybutyrate, that correlates with the oxidoreduction state of the liver mitochondrial compartment. Clinical data obtained in those studies revealed that the ratio below 0.25 indicates irreversible change of the liver mitochondria, that is a sign of the liver death. In this level severe coagulopathy appears with the laboratory data such as prothrombin time activity less than 30% and an abrupt decrease in platelets in the peripheral blood. In our experimental study we have analyzed a significance of persistent but reversible decrease of the liver energy charge and arterial ketone body ratio, under that animals do not die immediately, for inducing lung edema, that is an early symptom of MOF in severe infection. The persistent low energy state of the liver enhances the productivity of TNF and superoxide from the kupfer cell. Higher levels of peripheral TNF depending on release of TNF from the liver enhances activities of cytokines and gives damages to the lung endothelium. Thus, the lung edma is produced and disturbance of the liver tissue oxidation, in turn, causes further decreases in the arterial ketone body ratio and the liver energy charge, proceeding to the MOF malignant cycle.
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