| Project/Area Number |
09672338
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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 |
応用薬理学・医療系薬学
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
KASUYA Yasuji Tokyo University of Pharmacy and Life Science, School of Pharmacy, Professor, 薬学部, 教授 (90096686)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBASAKI Hiromi Tokyo University of Pharmacy and Life Science, School of Pharmacy, Assistant, 薬学部, 助手 (20206121)
FURUTA Takashi Tokyo University of Pharmacy and Life Science, School of Pharmacy, Associate Professor, 薬学部, 助教授 (70120152)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | cortisol / cortisone / stabel isotope methodology / 11β-HSD actitity / urinary cortisone / cortisol ratio / hypertension / GC-MS-SIM / pharmacokinetics / 重水素標識コルチゾール / 重水素標識コルチゾン / GC-MS分析 / 速度論的解析 / 尿中代謝物 / ヒトin vivo酵素活性 / GC-MS 分析 / ヒト in vivo 酵素活性 / 高血圧 / 重水素標識体 / GC-MS / IIβ-HSD |
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| Research Abstract |
One of the most unique advatages of the use of isotopically labeled compounds as tracers is that an endogenous compound and its exogenously administered stable isotopically labeled analog are separately measurable by using mass spectrometry.
This study is associated with a new approach using stable isotope methodology in evaluating 11β-HSD activities in vivo based on urinary excretion of unconjugated cortisol and cortisone. The method involved the measurement of stable isotopically labeled cortisol with ィイD12ィエD1H and its labeled metabolite, cortisone-ィイD12ィエD1H by GC-MS simultaneously with endogenous cortisol and cortisone after oral administration of a few mg of ィイD12ィエD1H-labeled cortisol to normal human subjects.
This stable isotope approach offered unique advantages since it allowed to measure stable isotopically labeled cortisol and its labeled metabolite cortisone simultaneously with endogenous (unlabeled) cortisol and cortisone. Very important was the potential use of stable isotopically labeled cortisol in man as a tracer for the native cortisol to recognize the conversion of cortisol to cortisone in the kidney. Our results from the stable isotope methodology strongly suggest that the measurement of unconjugated cortisol and cortisone in urine is a significant advance in assessing renal 11β-HSD2 activity in man.
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