| Project/Area Number |
62570997
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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 |
Biological pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
UTSUMI Hideo School of Pharmaceutical Sciences, Department of Health Chemistry Associate Professor, 薬学部, 助教授 (20101694)
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| Co-Investigator(Kenkyū-buntansha) |
MURAYAMA Jun-ichiro Showa University, School of Pharmaceutical Sciences, Department of Health Chemis, 薬学部, 助手 (30095921)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1989: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | electron spin resonance / ESR / EPR / CT / imaging / liver / active oxygen / spin-label / pharmacokinetics / drug metabolism / ESRイメ-ジング / スビンラベル / 肝ミクロソーム / ESRイメージング法 / in vivoESR / ニトロキシド還元反応 |
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| Research Abstract |
Stable nitroxide radicals are widely used as imaging reagents for in vivo, in situ, and in vitro ESR measurements. Thus the following experiments were carried out to develop in situ and in vivo ESR imaging technique of liver function.
(1) NADPH-induced nitroxide reduction in rat liver microsomes was investigated with an ESR spectrometer. Four stearic acids bearing nitroxide at a different position were synthesized and incorporated into the microsomal membranes. Comparison of reduction rate among 4 stearic acids suggested that the active center of the reduction system should be localized at 7- 12th position of the corresponding stearic acid. The measurements using phospholipids bearing nitroxide indicated the occurrence of a specific interaction of the reduction system with phosphatidic acid in microsomal membranes.
(2) The effects of surrounding air on NADPH-induced redox system was measured the change of ESR signal in microsomes under N_2 and O_2 gas. It was found that reduced form of the corresponding nitroxide should be reoxidized under O_2.
(3) The presence of active oxygen suppressed ESR signal reduction induced with NADPH in liver microsomes.
(4) In vivo and in situ ESR signals were successively obtained in the hepatic domain of whole mouse intravenously administered with nitroxide radical. The hepatic clearance of nitroxide in liver was estimated.
(5) The equipments and programs for an ESR imaging technique were manufactured by ourselves. The results made it possible to measure liver function with in vivo ESR imaging technique.
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