2006 Fiscal Year Final Research Report Summary
Analysis of free radical reactions in diseases model animals using in vivo ESRI
| Project/Area Number |
15087206
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Kyushu University |
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Principal Investigator |
USUMI Hideo Kyushu University, Faculty of Pharmaceutical Sciences, Professor, 大学院薬学研究院, 教授 (20101694)
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| Co-Investigator(Kenkyū-buntansha) |
TAKESHITA Keizo Sojo University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70175438)
KOSHIISHI Ichiro Nihon Pharmaceutical University, Professor, 主任教授 (20170235)
ICHIKAWA Kazuhiro Kyushu University, Faculty of Pharmaceutical Sciences, Associate Professor, 大学院薬学研究院, 助教授 (10271115)
YAMADA Keni-chi Kyushu University Faculty of Pharmaceutical Sciences, Assistant Professor, 大学院薬学研究院, 助教授 (60346806)
YASUKAWA Keiji Kyushu University Faculty of Pharmaceutical Sciences, Assistant Professor, 大学院薬学研究院, 助手 (80372738)
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| Project Period (FY) |
2003 – 2006
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| Keywords | reactive oxygen species / free radical / redox / electron spin resonance / life-related diseases / cancer / molecular imaging / MRI |
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| Research Abstract |
Free radical is reportedly associated with various diseases such as diabetes, hypertension, cerebrovascular accident, and cancer. In this study, we investigated the relationship between free radical generation and the initiation/development of diseases using in vivo ESR/spin probe technique. The ESR signal decay rate of MC-PROXYL, which is a membrane-permeable nitroxyl probe, in N-diethylnitrosoamine (DEN)-treated group is enhanced compared with that in control group, while the ESR signal decay rate of carbamoyl-PROXYL, which is a less membrane-permeable probe, in DEN-treated group is not changed, suggesting that reactive oxygen species is generated at the intracellular compartment of liver in DEN-treated rat.
OMRI is a newly developed imaging apparatus, which enables us to get free radical images with higher space resolution and shorter measuring time. We developed the molecular imaging system that is to visualize the redox reactions between in cell and out of cell simultaneously with
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^<14>N-or ^<15>N-labeled nitroxyl probes. Phantom objects containing ascorbic acid-encapsulated liposomes with membrane-permeable radicals but not membrane-impermeable ones show a time-dependent decrease of the OMRI image intensity. This OMRI system was applied to the in vivo free radical detection of experimental disease models such as NSAIDs-induced gastric ulcer and ulcerative colitis, and in vivo mapping of enhanced radical generation at the intra-cellular compartment and/or the extra-cellular compartment that was induced by the development of disease was obtained
However, the images of 0.015 T OMRI have low time and space resolution, resulting in the inaccurate anatomical information because its MRI magnetic field is too low. So, in this study sample transport OMRI system having 0.4 T was developed. The clear image of the phantom, which is composed of cylindrical grass tube (diameter 2.0 mm, wall thickness 0.35 mm) and rectangular container filled with nitroxyl radical solution, was obtained using this sample transport OMRI Less
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