| Project/Area Number |
62304066
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | Teikyo University |
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Principal Investigator |
OKADA Kazuo Prof of Anesthesiology. Faculty of Medicine. Teikyo University, 医学部麻酔科, 教授 (30082093)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKE Tamotsu Prof of Anesthesiology. Tokyo Medical College, 麻酔科, 教授 (90074476)
OZAWA Takayuki Prof of Biochemistry. Faculty of Medicine. Nagoya University, 医学部第二生化学, 教授 (80022771)
YOSHITAKE Junichi Prof of Anesthesiology. Faculty of Medicine. Kyushu University, 医学部麻酔科, 教授 (10041386)
YOSHIMURA Nozomu Prof of Anesthesiology. Faculty of Medicine. Kagoshima University, 医学部麻酔科, 教授 (60041399)
菊田 好則 帝京大学, 医学部麻酔科, 助手 (30129994)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Lysosome enzyme / Dichloroacetate / Endotoxin shock / Neutrophils / Leucotoxin / Tissue Po_2 / エンドトキシン・ショック / ミトコンドリヤ / ロイコトキシン / 活性酵素 / 組織酸素分圧 / ライソゾーム酵素 / 細胞内エネルギー / ミトコンドリヤ膜 / ロイコトキシン(9.10ーエポキシー12ーオクタデセン酸) / 好中球 |
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| Research Abstract |
Metabolic responses to shock are primarily influenced by factors such as the ability of the organ to autoregulate its blood flow and its ongoing functional activity. We have investigated the availability of oxygen measurement sensors in tissue. The tissue PO_2 in the brain was rather well maintained but progressively decreased in the conjunctival PO_2.
Energry failure and loss of regulatory membrane function occur when oxygen availability becomes critically compromised. Under these circunstances anaerobic glycolysis played the main role in maintaining cellular integrity. Dichloroacetate effectively improved energy production such as ATP in such a situation. Both drum shock and endotoxin shock models were applied to investigate the change of energy level. Urinastatin and Ca-blocker were effective from the point of energy preservation under shock circumstances.
Lysosome becomes fragile as the shock advanced. Several lysosomal enzymes were measured in the blood during hemorrhagic shock. Proteolytic enzymes were released from lysosome and morph-ological changes in lysosome became significant in the severe stages of shock.
Neutrophils played an important role for the homeostasis of the body, but during shock they activeated cascade systems such as conpliment oxgen radicals or proteolytic enzymes. An interesting finding obtained by this project was that not only activating cascade systen, but also a peculiar toxic substance called "Leucotoxin" was produced from neutrophils. This substance was analyzed chemically and determined to be linoleate epoxide. Both microsomal NADPH-cytochrome P-450 and NADPH oxidase contributed the production of this toxic substance. These results may be useful for further advances in pathophysiology and in the treatment of shock.
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