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Real Time Analysis of Drug-Diffusion in Muscle with in vivo ESR-Spectroscopy

Research Project

Project/Area Number 02670986
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionShowa University

Principal Investigator

HAMADA Akira  Showa University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50053781)

Co-Investigator(Kenkyū-buntansha) MIURA Yuri  Showa University, School of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (00216574)
TAKESHITA Keizo  Showa University, School of Pharmaceutical Sciences, Lecturer, 薬学部, 講師 (70175438)
UTSUMI Hideo  Showa University, School of Pharmaceutical Sciences, Assoc.Professor, 薬学部, 助教授 (20101694)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsESR / Nitroxide / Diffusion / Spin-Label / Ischemia-Reperfusion / Imaging / in vivo ERS / 薬物担体 / PDS / リポソ-ム / 筋肉 / LーバンドESR / ニトロキシド化合物 / スピンクリアランス / 筋肉内薬物動態 / 炎症 / 虚血 / 再潅流
Research Abstract

In order to utilize in vivo ESR-CT for studying drug-distribution and free radical reaction in biological system, we tried to measure ESR spectra of nitroxides administered into femoral muscle in mice, and obtained the following results.
1. Diffusion of spin-labeled compounds in muscle : Spin-labeled compound was injected into femoral muscle in mice.The resulting ESR spectrum seemed to be consisted of several components, which was due to different concentration of spin-labeled compound each other. Analysis of the spectrum with computer simulation indicated that the diffusion of nitroxide compounds in femoral muscle could be monitored with in vivo ESR. The signal of amino-TEMPO in femoral muscle of mice was decayed during occlusion, while that of Carbamoyl-PROXYL decreased only after reperfusion, suggesting that amino-TEMPO lose their paramagnetism in femoral muscle and Carbamoyl-PROXYL was transferred from muscle to blood.
2. ESR-CT system : One dimensional imaging of nitroxide administered into femoral muscle of mice was performed, suggesting that in vivo ESR-CT system may be applied to the study of drug-delivery-system.
3. Nitroxide reduction by ischemia-reperfusion injury : We prepared ischemia-reperfusion injury model by occlusion and reperfusion of the femoral thigh with a thread. The effects of ischemia-reperfusion on the reduction of nitroxides in femoral muscle were investigated by in vivo ESR, suggesting that nitroxides were reduced by active oxygen species produced by ischemia-reperfusion.
4. Improvement of ESR-CT system : To analyze the ESR spectrum containing several signals, spectral-special imaging system was developed.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 内海 英雄、濱田 昭: "スピンラベル法" 活性酸素・フリーラジカル. 2. 767-773 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 増田 貞夫、内海 英雄,濱田 昭: "L-Band ESRによるスピンラベル剤の筋肉内挙動の解析" 磁気共鳴と医学. 2. 69-74 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 増水 章季,建部 卓司,増田 貞夫,内海 英雄,武藤 江美子,濱田 昭,: "ESR-CT装置の試作" 磁気共鳴と医学. 2. 63-68 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.MIURA,H.UTSUMI and A.HAMADA: "EFFECTS OF INSPIRED OXYGEN CONCENTRATION ON IN VIVO REDOX REACTION OF NITROXIDE RADICALS IN WHOLE MICE" Biochemical and Biophysical Research Communications. 182. 1108-1114 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.MIURA,H.UTSUMI and A.HAMADA: "Antioxidant Activity of Nitroxide Radicals in Lipid Peroxidation of Rat Liver Microsomes" ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS. 300. 148-156 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.TAKESHITA,H.UTSUMI and A.HAMADA: "WHOLE MOUSE MEASUREMENT OF PARAMAGNETISM-LOSS OF NITROXIDE FREE RADICAL IN LUNG WITH A L-BAND ESR SPECTROMETER" BIOCHEMISTRY INTERNATIONAL. 29. 17-24 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.UTSUMI,S.MASUDA,E.MUTO and A.HAMADA: "OXIDATIVE DAMAGE AND REPAIR Chemical,Biological and Medical Aspects" Pergamon Press, 6 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.TAKESITA,S.MASUDA,Y.MIURA,H.UTSUMI and A.HAMADA: "OXYGEN RADICALS" EXCERPTA MEDICA, 12 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.UTSUMI, and A.HAMADA: "Spin-Labeling Method in Japanese" Journal of Active Oxygen & Free Radicals. 2. 767-773 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] S.MASUDA, H.UTSUMI, and A.HAMADA: "in vivo ESR Study on Diffusion of Spin-Labeled Compounds in Femoral Muscle in Japanese" Magnetic Resonance in Medicine. 2. 69-74 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.MASUMIZU, T.TATEBE, S.MASUDA, H.UTSUMI, E.MUTO, and A.HAMADA: "Trial Manufacture of ESR-CT Apparatus in Japanese" Magnetic Resonance in Medicine. 2. 63-68 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.MIURA, H.UTSUMI, and A.HAMADA: "Effects of Inspired Oxygen Concentration on in vivo Redox Reaction of Nitroxide Radicals" Biochem. Biophys. Res.Commn.182. 1108-1114 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.MIURA, H.UTSUMI, and A.HAMADA: "Antioxidant Activity of Nitroxide Radicals in Lipid Peroxidation of Rat Liver Microsomes" Arch. Biophem. Biophys.300. 148-156 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.TAKESHITA, H.UTSUMI, and A.HAMADA: "Whole Mouse Measurement of Paramagnetism-Loss of Nitroxide Free Radical in Lung with a L-band ESR Spectrometer" Biochem. Interaction. 29. 17-24 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.MIURA,H.UTSUMI and A.HAMADA: "EFFECTS OF INSPIRED OXYGEN CONCENTRATION ON VIVO REDOX REACTION OF NITROXIDE RADICALS IN WHOLE MICE" Biochemical and Biphysical Research Communications. 182. 1108-1114 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.MIURA,H.UTSUMI and A.HAMADA: "Antioxidant Activity of Nitroxide Radicals in Lipid Peroxidation of Rat Liver Microsomes" ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS. 300. 148-156 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.TAKESHITA,H.UTSUMI and A.HAMADA: "WHOLE MOUSE MEASUREMENT OF PARAMAGNETISMーLOSS OF NITROXIDE FREE RADICAL IN LUNG WITH A LーBAND ESR SPECTROMETER" BIOCHEMISTRY INTERNATIONAL. 29. 17-24 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 増水 章季: "ESRーCT装置の試作" 磁気共鳴と医学. 2. 63-98 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 増田 貞夫: "LーBand ESRによるスピンベル剤の筋肉内挙動の解析" 磁気共鳴と医学. 2. 69-74 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Keizo Takeshita: "ESR Measurement of Radical Clearance in Lung of Whole Mouse" Biochem.Biophys.Res.Commun.177. 874-880 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yuri Miura: "Effects of Inspired Oxygen Concentration on in vivo Redox Reaction of Nitroxide Radicals in Whole Mice" Biochem.Biophys.Res.Commun.182. 1108-1114 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hideo Utsumi: "In Vivo ESR Measurement of Radical Reaction in Whole MiceーInfluence of Inspired Oxygen and IschemiaーReperfusion Injury on Nitroxide Reductionー" Free Rad.Res.Commun.

    • Related Report
      1991 Annual Research Report
  • [Publications] 内海 英雄: "電子スピン共鳴スペクトル装置" ファ-ムテクジャパン. 6(11). 1-7 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 内海 英雄: "ラット肝ミクロソ-ムにおけるニトロキシドラジカル還元反応と活性酸素" 磁気共鳴と医学. 1. 125-129 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hideo Utsumi: "in vivo ESR measurement of free radicals in whole mice" Biochem.Biophys.Res.Comm. 172. 1342-1348 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 増田 貞夫: "LーBand ESRによるスピンラベル剤の筋肉内挙動の解析" 磁気共鳴と医学. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hideo Utsumi: "in vivo ESR studies on pharmacokinetics of nitroxide radicals in whole mice" Oxidative Damage & Repair. (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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