1992 Fiscal Year Final Research Report Summary
Therapeutic trials for progressive muscular dystrophy by using mdx mice
| Project/Area Number |
03670426
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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 |
Neurology
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| Research Institution | Toho University School of Medicine |
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Principal Investigator |
KURIHARA Teruyuki M.D.Toho Univ.Professor, 医学部, 教授 (80098607)
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| Co-Investigator(Kenkyū-buntansha) |
KISHI Masahiko M, D, Toho Univ. Assistant, 医学部, 助手 (50204847)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Mdx Mouse / Bestation / Mexiletine / Diphenylhydantoin / Dantrolene Na / Drug Effect / Resting Membrane Potential / Electrical Myotonia |
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| Research Abstract |
Duchenne's muscular dystrophy and X chromosome-linked mouse mutant (mdx) have been found to have the same defect of dystrophin in the muscle surface membrane. Intracellular recordings from the mdx mouse hemidiaphragm preparations revealed a group of muscle fibers with low resting membrane potentials (RMP) and electrical myotonia in about 30 % of the impaled muscle fibers at low temperature below 26ﾟC. The purpose of this study is to find effective medications to improve these physiological abnormalities of mdx mice.
In 1991 we have studied the effect of bestatin, mexyletine, and diphenylhydantoin on mdx mouse hemidiaphragm preparations. The intracellular recordings revealed that both bestatin and mexyletine improved low RMP, but diphenylhydantoin did not imprvove low RMP. All the above three medications suppressed electrical myotonia of mdx mice.
Bertorini reported that dantrolene Na reduced serum CK levels and suppressed the progression of muscle weakness in Duchenne's muscular dystrophy in 1991. Therefore, we also applied this medication to mdx mice in 1992. Dantorolene Na was given to mdx mice intraperitoneally for two weeks with a dose of 10 mg/day. We also studied the in vitro effect of dantrolene Na on mdx mouse hemidiaphragm preparations with a concentration of 10mg/1 in Tyrode's solution. The results showed that dantrolene Na did not improve low RMP of mdx mice, nor suppressed electrical myotonia.
In conclusion only bestation and mexiletine improved low RMP of mdx mice and suppressed electrical myotonia among the four medications we have tested for possible therapeutic usage.
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