Development of Local Drug Therapy on the Inner Ear

Research Project

Project/Area Number	11470360
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Otorhinolaryngology
Research Institution	Kansai Medical University
Principal Investigator	YAMASHITA Toshio Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (10077654)
Co-Investigator(Kenkyū-buntansha)	IWAI Hiroshi Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 講師 (10232638) DOI Tadashi Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 講師 (60288826) KURIYAMA Hiromichi Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 講師 (90268350) KOMEDA Mototane Kansai Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (20319619)
Project Period (FY)	1999 – 2001
Project Status	Completed (Fiscal Year 2001)
Budget Amount *help	¥8,400,000 (Direct Cost: ¥8,400,000) Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000) Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000) Fiscal Year 1999: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywords	osmotic pump / drug delivery / cochlea / kanamycin / ototoxicity / steroid / NO / カナマイシン / カルシウムイオン / NO合成酵素 / 薬剤性難聴 / 局所治療 / モルモット / 蝸牛 / ABR
Research Abstract	We set the researching project regarding to the local drug therapy on the inner ear. On the entire project, an animal model with drug-infusing system to the unilateral cochlea was used. Drug infusion was perfonned with an osmotic pump connecting to catheter which lead drug to the cochiear scala tynlpani. Infusion of artificial perilymph as a control study demonstrated no damage of cochlea. in both electrophysiology and cochlear cytology. Ototoxicity modei was made with kanamycin and ethacrynic acid on the bilaterai cochlea. As an experimental agent, ciexamethasone showed protective effect, against kanamycin-induced ototoxicity in the cochlca. The group of drug infusion two days prior to kanamycin admininistration led more protective effect than the group of drug infusion started the same day as kanamycin adrninistration. The other agent, iNOS inhibitor sbowed the protective effect on the kanamycin- induced trauma. Additional experimcnt using NO specific fluoresccnt dye. DAP-2DA showed reduction of kanamycin-induced NO synthesis on experirncntal side comparing to that on control side. We have also evaluated the effects on calcium free periiymphatic solution. NMDA receptor antagomst and cocktail of neurotrophirls, and determined their adequate concentrations.