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Molecular biological investigation for the mechanisms and treatment of NO induced inner ear damage

Research Project

Project/Area Number 12470357
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

TAKUMIDA Masaya  Hiroshima Univeristy, Medical Hospital, assistant professor, 医学部附属病院, 講師 (00179590)

Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥9,600,000 (Direct Cost: ¥9,600,000)
Keywordsinner ear / free radical / nitric oxide / reactive oxygen species / apoptosis / neurotrophine / gentamicin / treatment / 抗酸化剤 / リポポリサッカライド
Research Abstract

The aim of this study is to investigate the effects of free radicals (NO, ROS) to the inner ear disorders and to develop the new treatments for the inner ear disease by modulating and/or inhibit the various steps of the mechanisms of inner ear disorders.
As a result, certain stimuli induce the formation of free radicals, such as NO, ROS, resulting in a damage of inner ear. Subsequently, the sensory cells began to death by apoptosis. Calpain and caspase may play an important role for the apoptosis. These mechanisms were suggested to be a common pathway for almost all inner ear disorders. Based on these results, we investigated the attenuation of inner ear disorders by scavenging free radicals, inhibition of caspase or calpain and the addition of neurotrophines. All drugs used limited the hair cell damage and the combinations of drugs, such as inhibition of free radicals + neurotrophine, inhibition of free radicals + calpain or caspase inhibitors, had a significantly stronger preventive effect on haii cell damage. Based on these basic research, we have applied radical scavengers (rebamipide, vitamin C, glutathione) to the poor controlled Meniere s disease. The results of this clinical trial is sufficient revealing control of vertigo is 84% and improved rate of hearing loss was 44%.
These results were presented at meeting (23th meeting of the Japan Society of Inflamaiion and Regeneration, 10th, 11th and 12th meeting of the Otological Society of Japan, 59th, 60th and 61th meeting of Japan Society for Equilibrium Reseach, 37th Workshop on Inner Ear Biology, 20th meeting of Japan Society of Immunology & Allergology in Otolaryngology, 64th meeting of Society of Practical Otolaryngology) and were presented by 19 papers

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Takumida M: "Direct evidence of nitric oxide production in the guinea pig vestibular sensory cells"Acta Otolaryngol. 120. 34-38 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Localization of soluble guanylate cyclase activity in the guinea pig inner ear"Acta Otolaryngol. 120. 28-33 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Lipopolysaccharide-induced expression of inducible nitric oxide synthase in the guinea pig organ of Corti"Hear Res. 140. 91-98 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Glutamate-induced production of nitric oxide in guinea pig vestibular sensory cells"Acta Otolaryngol. 120. 466-472 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 工田昌矢: "抗酸化剤によるCDDP難聴の治療"耳鼻臨床. 93. 533-539 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Popa R: "Otoprotectant minimizes hearing defects caused by Pseudomonas aeruginosa exotoxin A"Acta Otolaryngol. 120. 350-358 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Nitric oxide in guinea pig vestibular sensory cells following gentamicin exposure in vitro"Acta Otolaryngol. 121. 346-350 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Pharmacological models for inner ear therapy with emphasis on nitric oxide"Acta Otolaryngol. 121. 16-20 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Direct evidence of nitric oxide production in the guinea pig organ of Corti"Acta Otolaryngol. 121. 342-345 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Detection of nitric oxide in guinea pig inner ear, using combination of aldehyde fixative and DAF-2DA"Acta Otolaryngol. 121. 460-464 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Popa A: "Localization of nitric oxide synthase isoforms in the human cochlea"Acta Otolaryngol. 121. 454-459 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 工田昌矢: "めまいの薬物療法"耳喉頭頚. 74. 94-99 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Simultaneous detection of both nitric oxide and reactive oxygen species in Guinea pig vestibular sensory cells"ORL. 64. 143-147 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Nitric oxide in the inner ear"Curr Opin Neurol. 15. 11-15 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Brain-derived neurotrophic factor and nitric oxide synthase inhibitor protect the vestibular organ against gentamicin ototoxicity"Acta Otolaryngol. 122. 10-15 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 工田昌矢: "内耳障害と一酸化窒素"耳喉頭頚. 74. 255-264 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 工田昌矢: "めまいの薬物療法"MB ENT. 13. 46-51 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 工田昌矢: "前庭器障害とNO"Equiribrium Res. 61. 99-103 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Neuroprotection of vestibular sensory cells from gentamicin ototoxicity obtained using nitric oxide synthase inhibitors, reactive oxygen species scavengers, brain-derived neurotrophic factors and calpain inhibitors"Acta Otolaryngol. 123. 8-13 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Anniko M: "Functional morphology of the normal peripheral vestibular system (in Physiology of the Ear)"SINGULAR THOMSON LEARNING. 481-514 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M: "Direct evidence of nitric oxide production in the guinea pig vestibular sensory cells."Acta Otolaryngol (Slockh). 120. 34-38 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M, Popa R, Zhang DM: "Localization of solubl guanylale cyclase activity in the guinea pig inner ear."Acta Otolaryngol (Slockh). 120. 28-33 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M, Popa R, Zhang DM: "Lipopolysaccharide-induced expression of inducible nitric oxide synthase in the guinea pig organ of Corti."Hear Res. 140. 91-98 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M: "Glutamate-induced production of nitric oxide in guinea pig vestibular sensory cells."Acta Otolaryngol (Slockh). 120. 466-472 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Yajin K: "Treatment of cisplatin olotoxicity by anti-oxidan drugs."Pracl Otol (Kyoto). 93. 533-539 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Popa R, Anniko M, Takumida M: "Otoprotectant minimizes hearing defects caused by Pseudomonas aeruginosa exotoxin A."Acta Otolaryngol (Slockh). 120. 350-358 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M: "Nitric oxide in guinea pig veslibular sensory cell following gentamicin exposure in vitro."Acta Otolaryngol (Slockh). 121. 346-350 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M, Popa E, Zhang DM: "Pharmacological models fat inner ear therapy with emphasis on nitric oxide"Acta Otolaryngol (Slockh). 121. 16-20 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M: "Direct evidence of nitric oxide production in the guinea pig organ of Corti."Acta Otolaryngol (Slockh). 121. 342-345 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takuraida M, Anniko M: "Detection of nitric oxide in guinea pig inner ear, using combination of aldehyde fixative and DAF-2DA."Acta Otolaryngol (Slockh). 121. 460-464 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Popa R, Anaiko M, Takumida M, Arnold W: "Localization of nitric oxide synthase isoforms in the human cochlea."Acta Otolaryngol (Slockh). 121. 454-459 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Medical treatment of vertigo."Otolaryngol Head Neck Surg (Tokyo). 74. 94-99 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M: "Simultaneous detection of both nitric oxide and reactive oxygen species in Guinea pig vestibular sensory cells."ORL. 64. 143-147 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M: "Nitric oxide in the inner ear."Curr Opin Neurol. 15. 11-15 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M: "Brain-derived neurotrophic factor and nitric oxide synthase inhibitor protect the vestibular organ against gentamicin ototoxicity."Acta Otolaryngol (Slockh). 122. 10-15 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Nitric oxide and inner ear disorders."Otolaryngol Head Neck Surg (Tokyo). 74. 255-264 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Medical treatment of vertigo."MB ENT. 13. 46-51 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Nitric oxide and vestibular disorders."Equiribrium Res.. 61. 99-103 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M, Anniko M, Shimizu A, Watanabe H: "Neuroprotection of vestibular sensory cells from gentamicin ototoxicity obtained using nitric oxide synthase inhibitors, reactive oxygen species scavengers, brain-derived neurotrophic factors and calpain inhibitors."Acta Otolaryngol (Slockh). 123. 8-13 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Anniko M.: "Functional morphology of the normal peripheral vestibular system (in Physiology of the Ear)"SINGULAR THOMSON LEARNING. 481-514 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takumida M: "Simultaneous detection of both nitric oxide and reactive oxygen species in Guinea pig vestibular sensory cells"ORL. 64. 143-147 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takumida M: "Nitric oxide in the inner ear"Curr Opin Neurol. 15. 11-15 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takumida M: "Brain-derived neurotrophic factor and nitric oxide synthase inhibitor protect the vestibular organ against gentamicin ototoxicity"Acta Otolaryngol. 122. 10-15 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 工田昌矢: "内耳障害と一酸化窒素"耳喉頭頸. 74. 255-264 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 工田昌矢: "前庭器障害とNO"Equilibrium Res. 61. 99-103 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takumida M: "Neuroprotection of vestibular sensory cells from gentamicin ototoxicity obtained using nitric oxide synthase inhibitors, reactive oxygen species scavengers, brain-derived neurotrophic factors and calpain inhibitors"Acta Otolaryngol. 123. 8-13 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takumida M, Anniko M: "Nitric oxide in guinea pig vestibular sensory cells following gentamicin exposure in vitro"Acta Otolaryngol. 121. 346-350 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] takumida M, Anniko M, Popa R, Zhang DM: "Pharmacological models for inner ear therapy with emphasis on nitric oxide"Acta Otolaryngol. 121. 16-20 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takumida M, Anniko M: "Direct evidence of nitric oxide production in the guinea pig organ of Corti"Acta Otolaryngol. 121. 342-45 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takumida M, Anniko M: "Detection of nitric oxide in guinea pig inner ear, using a combination of aldehyde fixative and DAF-2DA"Acta Otolaryngol. 121. 460-464 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takumida M, Anniko M: "Brain-derived neurotrophic factor and nitric oxide synthase Inhibitor protect the vestibular organ against gentamicin ototoxicity"Acta Otolaryngol. 122. (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takumida M, Anniko M: "Simultaneous detection of both nitric oxide and reactive oxygen species in the guinea pig vestibular sensory cells"ORL. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Anniko M, Takumida M: "Physiology of the EAR ; Functional morphology of the normal vestibular system"SINGULAR THOMSON LEARNING. 689 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Popa R,Anniko M Takumida M: "Otoprotectant minimizes hearing defects caused by Pseudomonas aeruginosa exotoxin A"Acta Otolaryngol(Stockh). 120. 350-358 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takumida M,Anniko M: "Nitric oxide in guinea pig vestibular sensory cells following gentamicin exposure in vitro"Acta Otolaryngol(Stockh). (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takumida M,Anniko M: "Direct evidence of nitric oxide production in the guinea pig organ of Corti"Acta Otolaryngol(Stockh). (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takumida M,Anniko M: "Detection of nitric oxide in guinea pig inner ear, using combination of aldehyde fixative and DAF-2DA"Acta Otolaryngol(Stockh). (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Anniko M,Takumida M: "Physiology of the ear Chapter 21 Functional molphology of the normal peripheral vestibular system"Singular Thomson Learning. 689 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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