2003 Fiscal Year Final Research Report Summary
Effect of combination therapy consisting of copper and a chelator for Menkes disiease.
| Project/Area Number |
14570773
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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 |
Pediatrics
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| Research Institution | Teikyo University |
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Principal Investigator |
KODAMA Hiroko Medical School, Pediatrics, associated Prof., 医学部, 助教授 (00093386)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Ichiro Teikyo University, assistant prof., 医学部, 講師 (40091045)
MORI Yosuke International University of Health and welfare, assistant prof., 保健学部, 講師 (20328090)
NAKAMOTO Natsue Teikyo University, research assistant, 医学部, 助手 (20256043)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Menkes desease / chelator / Blood Brian Barrier / Copper enzyme / therapy |
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| Research Abstract |
[Object] Menkes disease is a disorder of copper transport. In patients with Menkes disease, copper accumulates in the intestine, kidney and blood brain barrier (B.B.B.) while the brain remains in a state of copper deficiency. The copper deficiency in the brain cannot be improved by copper injections, because the administered copper accumulates B.B.B. and cannot be transported to neurons. We investigated the effect of combination therapy with administrations of copper and sodium diethyldithiocarbamate (DEDTC), a lypophylic chelator, in the macular mouse.
[Methods] Four-week old macular mice that had been treated with 50 ug of CuCl_2 on the 7th day after birth were used. The mice were separated into three groups (group A, chelator + copper ; group B, copper ; group C, saline control). Mice in group A were treated with a subcutaneous injection of CuCl_2 (4 ug) and an intraperitoneal injections of DEDTC (0.2 mg/g) twice a week for 4 weeks and then sacrificed. Mice in group B were treated with only CuCl_22 in the same manner as group A. The brain, kidney and intestine were then dissected, and copper concentration and cytochrome C oxidase (CCO) activity were analyzed.
[Results & Conclusions] The copper concentration in the brain of group A was higher than that in group B and C. The CCO activity in the brain was highest in group A. The copper concentrations in the kidneys and intestines of group A were also higher than in group B and C. These results suggest that the chelator enables copper to pass through B.B.B. improving copper deficiency and CCO activity in the brain. However, the combination therapy worsens copper accumulation in the kidney.
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Research Products
(15 results)
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[Publications] Takahashi Y, Kako K, Kashiwabara S, Takehara A, Inada Y, Arai H, Nakada K, Kodama H, Hayashi J, Baba T, Munekata E: "Mammalian copper chaperone cox17p has an essential role in activation of cytochrome c oxidase and embryonic development"Molecular and Cellular Biology. 22(21). 7614-7621 (2002)
Description
「研究成果報告書概要(欧文)」より
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