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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 劉興華 | |
dc.contributor.author | Ting-Hua Yang | en |
dc.contributor.author | 楊庭華 | zh_TW |
dc.date.accessioned | 2021-06-08T05:01:30Z | - |
dc.date.copyright | 2011-03-03 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-11-22 | |
dc.identifier.citation | Battista, R. A. (2005). Intratympanic dexamethasone for profound idiopathic sudden sensorineural hearing loss. Otolaryngol Head Neck Surg 132, 902-905.
Bergstrom, B. (1973). Morphology of the vestibular nerve. II. The number of myelinated vestibular nerve fibers in man at various ages. Acta Otolaryngol 76, 173-179. Bodmer, D., Brors, D., Pak, K., Gloddek, B., and Ryan, A. (2002). Rescue of auditory hair cells from aminoglycoside toxicity by Clostridium difficile toxin B, an inhibitor of the small GTPases Rho/Rac/Cdc42. Hear Res 172, 81-86. Burschka, M. A., Hassan, H. A., Reineke, T., van Bebber, L., Caird, D. M., and Mosges, R. (2001). Effect of treatment with Ginkgo biloba extract EGb761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients. Eur Arch Otorhinolaryngol 258, 213-219. Chandrasekhar, S. S. (2001). Intratympanic dexamethasone for sudden sensorineural hearing loss: clinical and laboratory evaluation. Otol Neurotol 22, 18-23. Chang, T. K., Chen, J., and Teng, X. W. (2006). Distinct role of bilobalide and ginkgolide A in the modulation of rat CYP2B1 and CYP3A23 gene expression by Ginkgo biloba extract in cultured hepatocytes. Drug Metab Dispos 34, 234-242. Cheng, P. W., Chen, C. C., Wang, S. J., and Young, Y. H. (2009). Acoustic, mechanical and galvanic stimulation modes elicit ocular vestibular-evoked myogenic potentials. Clin Neurophysiol 120, 1841-1844. Cheng, P. W., Lue, J. H., Lin, C. T., Day, A. S., and Young, Y. H. (2010). Assessment of gentamicin-induced vestibulotoxicity by click and galvanic vestibular-evoked myogenic potentials: a guinea pig investigation. Neurotoxicology 31, 121-125. Cheung, F., Siow, Y. L., Chen, W. Z., and O, K. (1999). Inhibitory effect of Ginkgo biloba extract on the expression of inducible nitric oxide synthase in endothelial cells. Biochem Pharmacol 58, 1665-1673. Choo, Y. B. (1984). Microscopic characteristics of round window problems in otology. Laryngoscope 94, 1-9. Colebatch, J. G. (2010). Sound conclusions? Clin Neurophysiol 121, 124-126. Colebatch, J. G., Halmagyi, G. M., and Skuse, N. F. (1994). Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57, 190-197. Corbacella, E., Lanzoni, I., Ding, D., Previati, M., and Salvi, R. (2004). Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures. Hear Res 197, 11-18. Curthoys, I. S. (2010a). A balanced view of the evidence leads to sound conclusions. A reply to J.G. Colebatch 'Sound conclusions?'. Clin Neurophysiol 121, 977-978. Curthoys, I. S. (2010b). A critical review of the neurophysiological evidence underlying clinical vestibular testing using sound, vibration and galvanic stimuli. Clin Neurophysiol 121, 132-144. Curthoys, I. S., Iwasaki, S., Chihara, Y., Ushio, M., McGarvie, L. A., and Burgess, A. M. (2010). The ocular vestibular-evoked myogenic potential to air-conducted sound; probable superior vestibular nerve origin. Clin Neurophysiol. Curthoys, I. S., Kim, J., McPhedran, S. K., and Camp, A. J. (2006). Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig. Exp Brain Res 175, 256-267. Davis, B., Qiu, W., and Hamernik, R. P. (2004). The use of distortion product otoacoustic emissions in the estimation of hearing and sensory cell loss in noise-damaged cochleas. Hear Res 187, 12-24. Davis, B., Qiu, W., and Hamernik, R. P. (2005). Sensitivity of distortion product otoacoustic emissions in noise-exposed chinchillas. J Am Acad Audiol 16, 69-78. Day, A. S., Lue, J. H., Yang, T. H., and Young, Y. H. (2007). Effect of intratympanic application of aminoglycosides on click-evoked myogenic potentials in Guinea pigs. Ear Hear 28, 18-25. De Burlet, H. M. (1924). Zur Innervation der Macula sacculi bei Saugetieren. Anat Anzig 58, 26-32. Diamond, B. J., Shiflett, S. C., Feiwel, N., Matheis, R. J., Noskin, O., Richards, J. A., and Schoenberger, N. E. (2000). Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 81, 668-678. Didier, A., and Cazals, Y. (1989). Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig. Hear Res 37, 123-127. Didier, A., Droy-Lefaix, M. T., Aurousseau, C., and Cazals, Y. (1996). Effects of Ginkgo biloba extract (EGb761) on cochlear vasculature in the guinea pig: morphometric measurements and laser Doppler flowmetry. Eur Arch Otorhinolaryngol 253, 25-30. Fernandez, C., Goldberg, J. M., and Abend, W. K. (1972). Response to static tilts of peripheral neurons innervating otolith organs of the squirrel monkey. J Neurophysiol 35, 978-987. Fetoni, A. R., Sergi, B., Ferraresi, A., Paludetti, G., and Troiani, D. (2004). alpha-Tocopherol protective effects on gentamicin ototoxicity: an experimental study. Int J Audiol 43, 166-171. Gianoli, G. J., and Li, J. C. (2001). Transtympanic steroids for treatment of sudden hearing loss. Otolaryngol Head Neck Surg 125, 142-146. Goldberg, J. M. (2000). Afferent diversity and the organization of central vestibular pathways. Exp Brain Res 130, 277-297. Goycoolea, M. V., Carpenter, A. M., and Muchow, D. (1987). Ultrastructural studies of the round-window membrane of the cat. Arch Otolaryngol Head Neck Surg 113, 617-624. Goycoolea, M. V., Muchow, D., and Schachern, P. (1988). Experimental studies on round window structure: function and permeability. Laryngoscope 98, 1-20. Gryglewski, R. J., Korbut, R., Robak, J., and Swies, J. (1987). On the mechanism of antithrombotic action of flavonoids. Biochem Pharmacol 36, 317-322. Guthrie, O. W. (2008). Aminoglycoside induced ototoxicity. Toxicology 249, 91-96. Halmagyi, G. M., Aw, S. T., Cremer, P. D., Curthoys, I. S., and Todd, M. J. (2001). Impulsive testing of individual semicircular canal function. Ann N Y Acad Sci 942, 192-200. Halmagyi, G. M., Fattore, C. M., Curthoys, I. S., and Wade, S. (1994). Gentamicin vestibulotoxicity. Otolaryngol Head Neck Surg 111, 571-574. Haynes, D. S., O'Malley, M., Cohen, S., Watford, K., and Labadie, R. F. (2007). Intratympanic dexamethasone for sudden sensorineural hearing loss after failure of systemic therapy. Laryngoscope 117, 3-15. Heinrich, U. R., Helling, K., Sifferath, M., Brieger, J., Li, H., Schmidtmann, I., and Mann, W. J. (2008). Gentamicin increases nitric oxide production and induces hearing loss in guinea pigs. Laryngoscope 118, 1438-1442. Heinrich, U. R., Selivanova, O., Brieger, J., and Mann, W. J. (2006). Endothelial nitric oxide synthase upregulation in the cochlea of the guinea pig after intratympanic gentamicin injection. Eur Arch Otorhinolaryngol 263, 62-68. Helling, K., Clarke, A. H., Watanabe, N., and Scherer, H. (2000). [Morphological studies of the form of the cupula in the semicircular canal ampulla]. HNO 48, 822-827. Hellstrom, S., Johansson, U., and Anniko, M. (1989). Structure of the round window membrane. Acta Otolaryngol Suppl 457, 33-42. Hibi, T., Suzuki, T., and Nakashima, T. (2001). Perilymphatic concentration of gentamicin administered intratympanically in guinea pigs. Acta Otolaryngol 121, 336-341. Hillman, D. E., and McLaren, J. W. (1979). Displacement configuration of semicircular canal cupulae. Neuroscience 4, 1989-2000. Ikeda, K., and Morizono, T. (1988). Changes of the permeability of round window membrane in otitis media. Arch Otolaryngol Head Neck Surg 114, 895-897. Ikeda, K., Sakagami, M., Morizono, T., and Juhn, S. K. (1990). Permeability of the round window membrane to middle-sized molecules in purulent otitis media. Arch Otolaryngol Head Neck Surg 116, 57-60. Iwasaki, S., Chihara, Y., Smulders, Y. E., Burgess, A. M., Halmagyi, G. M., Curthoys, I. S., and Murofushi, T. (2009). The role of the superior vestibular nerve in generating ocular vestibular-evoked myogenic potentials to bone conducted vibration at Fz. Clin Neurophysiol 120, 588-593. Iwasaki, S., McGarvie, L. A., Halmagyi, G. M., Burgess, A. M., Kim, J., Colebatch, J. G., and Curthoys, I. S. (2007). Head taps evoke a crossed vestibulo-ocular reflex. Neurology 68, 1227-1229. Jaeger, R., Takagi, A., and Haslwanter, T. (2002). Modeling the relation between head orientations and otolith responses in humans. Hear Res 173, 29-42. Juhn, S. K., Hamaguchi, Y., and Goycoolea, M. (1989). Review of round window membrane permeability. Acta Otolaryngol Suppl 457, 43-48. Jung, H. W., Chang, S. O., Kim, C. S., Rhee, C. S., and Lim, D. H. (1998). Effects of Ginkgo biloba extract on the cochlear damage induced by local gentamicin installation in guinea pigs. J Korean Med Sci 13, 525-528. Kaptan, Z. K., Emir, H., Gocmen, H., Uzunkulaoglu, H., Karakas, A., Senes, M., and Samim, E. (2008). Ginkgo biloba, a free oxygen radical scavenger, affects inflammatory mediators to diminish the occurrence of experimental myringosclerosis. Acta Otolaryngol, 1-6. Kawabata, I., and Paparella, M. M. (1971). Fine structure of the round window membrane. Ann Otol Rhinol Laryngol 80, 13-26. Keithley, E. M., Ma, C. L., Ryan, A. F., Louis, J. C., and Magal, E. (1998). GDNF protects the cochlea against noise damage. Neuroreport 9, 2183-2187. Kobuchi, H., Droy-Lefaix, M. T., Christen, Y., and Packer, L. (1997). Ginkgo biloba extract (EGb761): inhibitory effect on nitric oxide production in the macrophage cell line RAW 264.7. Biochem Pharmacol 53, 897-903. Kopke, R. D., Hoffer, M. E., Wester, D., O'Leary, M. J., and Jackson, R. L. (2001). Targeted topical steroid therapy in sudden sensorineural hearing loss. Otol Neurotol 22, 475-479. Korver, K. D., Rybak, L. P., Whitworth, C., and Campbell, K. M. (2002). Round window application of D-methionine provides complete cisplatin otoprotection. Otolaryngol Head Neck Surg 126, 683-689. Krieglstein, J., Beck, T., and Seibert, A. (1986). Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism. Life Sci 39, 2327-2334. Kudolo, G. B., Dorsey, S., and Blodgett, J. (2002). Effect of the ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and Type 2 diabetic subjects. Thromb Res 108, 151-160. Lalwani, A. K., Walsh, B. J., Reilly, P. G., Muzyczka, N., and Mhatre, A. N. (1996). Development of in vivo gene therapy for hearing disorders: introduction of adeno-associated virus into the cochlea of the guinea pig. Gene Ther 3, 588-592. Lautermann, J., Sudhoff, H., and Junker, R. (2005). Transtympanic corticoid therapy for acute profound hearing loss. Eur Arch Otorhinolaryngol 262, 587-591. Lefebvre, P. P., and Staecker, H. (2002). Steroid perfusion of the inner ear for sudden sensorineural hearing loss after failure of conventional therapy: a pilot study. Acta Otolaryngol 122, 698-702. Lesniak, W., Pecoraro, V. L., and Schacht, J. (2005). Ternary complexes of gentamicin with iron and lipid catalyze formation of reactive oxygen species. Chem Res Toxicol 18, 357-364. Liu, H. Y., Chi, F. L., and Gao, W. Y. (2008). Taurine attenuates aminoglycoside ototoxicity by inhibiting inducible nitric oxide synthase expression in the cochlea. Neuroreport 19, 117-120. Lopez-Gonzalez, M. A., Lucas, M., Delgado, F., and Diaz, P. (1998). The production of free oxygen radicals and nitric oxide in the rat cochlea. Neurochem Int 33, 55-59. Lue, J. H., Day, A. S., Cheng, P. W., and Young, Y. H. (2009). Vestibular evoked myogenic potentials are heavily dependent on type I hair cell activity of the saccular macula in guinea pigs. Audiol Neurootol 14, 59-66. Maitra, I., Marcocci, L., Droy-Lefaix, M. T., and Packer, L. (1995). Peroxyl radical scavenging activity of Ginkgo biloba extract EGb761. Biochem Pharmacol 49, 1649-1655. Malgrange, B., Rigo, J. M., Coucke, P., Thiry, M., Hans, G., Nguyen, L., van de Water, T. R., Moonen, G., and Lefebvre, P. P. (2002). Identification of factors that maintain mammalian outer hair cells in adult organ of Corti explants. Hear Res 170, 48-58. Manzari, L., Burgess, A. M., and Curthoys, I. S. (2010a). Dissociation between cVEMP and oVEMP responses: different vestibular origins of each VEMP? Eur Arch Otorhinolaryngol 267, 1487-1489. Manzari, L., Tedesco, A., Burgess, A. M., and Curthoys, I. S. (2010b). Ocular vestibular-evoked myogenic potentials to bone-conducted vibration in superior vestibular neuritis show utricular function. Otolaryngol Head Neck Surg 143, 274-280. Marcocci, L., Maguire, J. J., Droy-Lefaix, M. T., and Packer, L. (1994). The nitric oxide-scavenging properties of Ginkgo biloba extract EGb761. Biochem Biophys Res Commun 201, 748-755. Mason, S., Garnham, C., and Hudson, B. (1996). Electric response audiometry in young children before cochlear implantation: a short latency component. Ear Hear 17, 537-543. McFadden, S. L., Ding, D., Salvemini, D., and Salvi, R. J. (2003). M40403, a superoxide dismutase mimetic, protects cochlear hair cells from gentamicin, but not cisplatin toxicity. Toxicol Appl Pharmacol 186, 46-54. Minor, L. B. (1999). Intratympanic gentamicin for control of vertigo in Meniere's disease: vestibular signs that specify completion of therapy. Am J Otol 20, 209-219. Murofushi, T., Curthoys, I. S., Topple, A. N., Colebatch, J. G., and Halmagyi, G. M. (1995). Responses of guinea pig primary vestibular neurons to clicks. Exp Brain Res 103, 174-178. Nakagawa, T., Yamane, H., Takayama, M., Sunami, K., and Nakai, Y. (1998). Apoptosis of guinea pig cochlear hair cells following chronic aminoglycoside treatment. Eur Arch Otorhinolaryngol 255, 127-131. Oberpichler, H., Beck, T., Abdel-Rahman, M. M., Bielenberg, G. W., and Krieglstein, J. (1988). Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. Pharmacol Res Commun 20, 349-368. Oyama, Y., Chikahisa, L., Ueha, T., Kanemaru, K., and Noda, K. (1996). Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. Brain Res 712, 349-352. Parnes, L. S., Sun, A. H., and Freeman, D. J. (1999). Corticosteroid pharmacokinetics in the inner ear fluids: an animal study followed by clinical application. Laryngoscope 109, 1-17. Paulson, D. P., Abuzeid, W., Jiang, H., Oe, T., O'Malley, B. W., and Li, D. (2008). A novel controlled local drug delivery system for inner ear disease. Laryngoscope 118, 706-711. Priuska, E. M., and Schacht, J. (1995). Formation of free radicals by gentamicin and iron and evidence for an iron/gentamicin complex. Biochem Pharmacol 50, 1749-1752. Priuska, E. M., and Schacht, J. (1997). Mechanism and prevention of aminoglycoside ototoxicity: outer hair cells as targets and tools. Ear Nose Throat J 76, 164-166, 168, 170-161. Punkt, K., Zaitsev, S., Park, J. K., Wellner, M., and Buchwalow, I. B. (2001). Nitric oxide synthase isoforms I, III and protein kinase-Ctheta in skeletal muscle fibres of normal and streptozotocin-induced diabetic rats with and without Ginkgo biloba extract treatment. Histochem J 33, 213-219. Rajaraman, G., Chen, J., and Chang, T. K. (2006). Ginkgolide A contributes to the potentiation of acetaminophen toxicity by Ginkgo biloba extract in primary cultures of rat hepatocytes. Toxicol Appl Pharmacol 217, 225-233. Reuse-Blom, S., and Drieu, K. (1986). [Effect of Ginkgo biloba extract on arteriolar spasm in rabbits]. Presse Med 15, 1520-1523. Rizzi, M. D., and Hirose, K. (2007). Aminoglycoside ototoxicity. Curr Opin Otolaryngol Head Neck Surg 15, 352-357. Robak, J., and Gryglewski, R. J. (1988). Flavonoids are scavengers of superoxide anions. Biochem Pharmacol 37, 837-841. Roland, P. S. (2003). Characteristics of systemic and topical agents implicated in toxicity of the middle and inner ear. Ear Nose Throat J 82 Suppl 1, 3-8. Rosengren, S. M., McAngus Todd, N. P., and Colebatch, J. G. (2005). Vestibular-evoked extraocular potentials produced by stimulation with bone-conducted sound. Clin Neurophysiol 116, 1938-1948. Rosengren, S. M., Welgampola, M. S., and Colebatch, J. G. (2010). Vestibular evoked myogenic potentials: past, present and future. Clin Neurophysiol 121, 636-651. Rosenhall, U. (1972). Vestibular macular mapping in man. Ann Otol Rhinol Laryngol 81, 339-351. Rybak, L. P., and Ramkumar, V. (2007). Ototoxicity. Kidney Int 72, 931-935. Schachern, P. A., Paparella, M. M., Duvall, A. J., 3rd, and Choo, Y. B. (1984). The human round window membrane. An electron microscopic study. Arch Otolaryngol 110, 15-21. Sha, S. H., and Schacht, J. (1999). Stimulation of free radical formation by aminoglycoside antibiotics. Hear Res 128, 112-118. Sha, S. H., and Schacht, J. (2000). Antioxidants attenuate gentamicin-induced free radical formation in vitro and ototoxicity in vivo: D-methionine is a potential protectant. Hear Res 142, 34-40. Sha, S. H., Taylor, R., Forge, A., and Schacht, J. (2001). Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals. Hear Res 155, 1-8. Shen, J., Wang, J., Zhao, B., Hou, J., Gao, T., and Xin, W. (1998). Effects of EGb761 on nitric oxide and oxygen free radicals, myocardial damage and arrhythmia in ischemia-reperfusion injury in vivo. Biochim Biophys Acta 1406, 228-236. Shi, C., Zhao, L., Zhu, B., Li, Q., Yew, D. T., Yao, Z., and Xu, J. (2009). Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against beta-amyloid peptide-induced toxicity in SH-SY5Y cells. Chem Biol Interact 181, 115-123. Slattery, W. H., Fisher, L. M., Iqbal, Z., Friedman, R. A., and Liu, N. (2005). Intratympanic steroid injection for treatment of idiopathic sudden hearing loss. Otolaryngol Head Neck Surg 133, 251-259. Smith, P. F., Zheng, Y., and Darlington, C. L. (2005). Ginkgo biloba extracts for tinnitus: More hype than hope? J Ethnopharmacol 100, 95-99. Staecker, H., Gabaizadeh, R., Federoff, H., and Van De Water, T. R. (1998). Brain-derived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss. Otolaryngol Head Neck Surg 119, 7-13. Stover, T., Yagi, M., and Raphael, Y. (1999). Cochlear gene transfer: round window versus cochleostomy inoculation. Hear Res 136, 124-130. Takumida, M., and Anniko, M. (2001). Nitric oxide in guinea pig vestibular sensory cells following gentamicin exposure in vitro. Acta Otolaryngol 121, 346-350. Takumida, M., Popa, R., and Anniko, M. (1999). Free radicals in the guinea pig inner ear following gentamicin exposure. ORL J Otorhinolaryngol Relat Spec 61, 63-70. Trayner, I. D., Rayner, A. P., Freeman, G. E., and Farzaneh, F. (1995). Quantitative multiwell myeloid differentiation assay using dichlorodihydrofluorescein diacetate (H2DCF-DA) or dihydrorhodamine 123 (H2R123). J Immunol Methods 186, 275-284. Uchino, Y., Sato, H., Sasaki, M., Imagawa, M., Ikegami, H., Isu, N., and Graf, W. (1997). Sacculocollic reflex arcs in cats. J Neurophysiol 77, 3003-3012. Uzun-Coruhlu, H., Curthoys, I. S., and Jones, A. S. (2007). Attachment of the utricular and saccular maculae to the temporal bone. Hear Res 233, 77-85. Wang, A. M., Sha, S. H., Lesniak, W., and Schacht, J. (2003a). Tanshinone (Salviae miltiorrhizae extract) preparations attenuate aminoglycoside-induced free radical formation in vitro and ototoxicity in vivo. Antimicrob Agents Chemother 47, 1836-1841. Wang, J., Van De Water, T. R., Bonny, C., de Ribaupierre, F., Puel, J. L., and Zine, A. (2003b). A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J Neurosci 23, 8596-8607. Wang, S. J., Weng, W. J., Jaw, F. S., and Young, Y. H. (2010). Ocular and cervical vestibular-evoked myogenic potentials: a study to determine whether air- or bone-conducted stimuli are optimal. Ear Hear 31, 283-288. Wei, X., Zhao, L., Liu, J., Dodel, R. C., Farlow, M. R., and Du, Y. (2005). Minocycline prevents gentamicin-induced ototoxicity by inhibiting p38 MAP kinase phosphorylation and caspase 3 activation. Neuroscience 131, 513-521. Welgampola, M. S., and Carey, J. P. (2010). Waiting for the evidence: VEMP testing and the ability to differentiate utricular versus saccular function. Otolaryngol Head Neck Surg 143, 281-283. Welgampola, M. S., Myrie, O. A., Minor, L. B., and Carey, J. P. (2008). Vestibular-evoked myogenic potential thresholds normalize on plugging superior canal dehiscence. Neurology 70, 464-472. Welgampola, M. S., Rosengren, S. M., Halmagyi, G. M., and Colebatch, J. G. (2003). Vestibular activation by bone conducted sound. J Neurol Neurosurg Psychiatry 74, 771-778. Wong, D. L., and Rutka, J. A. (1997). Do aminoglycoside otic preparations cause ototoxicity in the presence of tympanic membrane perforations? Otolaryngol Head Neck Surg 116, 404-410. Wu, W. J., Sha, S. H., and Schacht, J. (2002). Recent advances in understanding aminoglycoside ototoxicity and its prevention. Audiol Neurootol 7, 171-174. Wuyts, F. L., Furman, J., Vanspauwen, R., and Van de Heyning, P. (2007). Vestibular function testing. Curr Opin Neurol 20, 19-24. Yang, T. H., and Young, Y. H. (2005). Click-evoked myogenic potentials recorded on alert guinea pigs. Hear Res 205, 277-283. Ylikoski, J., Xing-Qun, L., Virkkala, J., and Pirvola, U. (2002). Blockade of c-Jun N-terminal kinase pathway attenuates gentamicin-induced cochlear and vestibular hair cell death. Hear Res 166, 33-43. Yoshikawa, T., Naito, Y., and Kondo, M. (1999). Ginkgo biloba leaf extract: review of biological actions and clinical applications. Antioxid Redox Signal 1, 469-480. Young, Y. H. (2006). Vestibular evoked myogenic potentials: optimal stimulation and clinical application. J Biomed Sci 13, 745-751. Young, Y. H., Nomura, Y., Okuno, T., and Hara, M. (1991). Clip electrode method for recording eye movements in experimental animals. Eur Arch Otorhinolaryngol 248, 331-334. Zhang, J., Fu, S., Liu, S., Mao, T., and Xiu, R. (2000). The therapeutic effect of Ginkgo biloba extract in SHR rats and its possible mechanisms based on cerebral microvascular flow and vasomotion. Clin Hemorheol Microcirc 23, 133-138. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23429 | - |
dc.description.abstract | 耳毒性是指因化學物質、藥物或某些外因性侵犯,造成內耳或相關神經系統的功能損害,主要症狀為聽力障礙、耳鳴、平衡障礙及眩暈。由於耳毒性傷害的初期臨床症狀不明顯,加上耳毒性物質種類繁多、對內耳功能影響的程度方式不一,而且過去研究耳毒性方法並不完全,導致準確性有偏差 。尤以今日又發展出耳內注射等新的給藥途徑,以往的耳毒性資料自需要重新再評估。舉例而言,以往的耳毒性動物實驗往往著重病理組織觀察,內耳功能監測未能涵蓋耳石器官 (橢圓囊及球囊),所以無法真實反映出耳毒性物質影響下的內耳狀態。即使至今,雖然聽力檢查的動物模型已完整建立,動物前庭功能的評估還是以行為觀察為主。有鑑於此,本論文主旨在建立天竺鼠的內耳測試系統,以檢測完整的內耳功能為目標。
首先,我們建立天竺鼠的眼性前庭誘發肌性電位 (oVEMP) 藉以評估橢圓囊功能。在安靜的環境下固定清醒天竺鼠,以手持振動器輕置於前額以刺激其前庭橢圓囊後,可於對側下眼外肌肉附近測得前庭眼反射造成的眼性前庭誘發肌性電位。實驗證明,耳內注射gentamicin破壞橢圓囊後,眼性前庭誘發肌性電位亦隨之消失。 其次,我們亦發展天竺鼠的頸性前庭誘發肌性電位 (cVEMP)以評估球囊功能;配合眼性前庭誘發肌性電位檢查,有效檢測所有耳石器官。我們分別選擇以氣倒音聲及骨導振動不同刺激產生前庭誘發肌性電位。實驗發現,120分貝以下的聲音刺激無法產生眼性前庭誘發肌性電位,而骨導振動刺激則能有效產生眼性前庭誘發肌性電位。當左耳灌注gentamicin引發耳毒性傷害後,所有天竺鼠均無法以振動刺激誘發源於左耳的眼性前庭誘發肌性電位,亦無法於左頸處產生受聲音刺激誘發的頸性前庭誘發肌性電位,但只有60%無法利用振動刺激誘發左頸處的頸性前庭誘發肌性電位。故推測聲音刺激誘發較合適於頸性前庭誘發肌性電位檢查,因為振動刺激可能會引起對側交叉反應引起偽陽性結果。眼性前庭誘發肌性電位檢查則適合以振動刺激誘發,聲音刺激的誘發率則不足,該結論亦與人類臨床報告結論相似。 接著,我們嘗試組合了聽性腦幹誘發反應 (auditory brainstem response)、溫差試驗(caloric test)及上述的眼性前庭誘發肌性電位、頸性前庭誘發肌性電位檢查,為天竺鼠進行完整的內耳功能檢測。相較於所有對照組 (未投藥的一邊正常耳)正常數值,所有受gentamicin耳毒性傷害的另一邊耳朵在聽性腦幹誘發反應均有聽力閾值上升現象,且其餘三者檢查全無反應。病理學檢查亦證實,受gentamicin耳毒性傷害的耳蝸及前庭組織耳毛細胞已大量死亡,與功能檢測結果相符。故利用我們建立的完整內耳功能檢測,的確能有效評估耳毒性物質對內耳器官的影響及傷害。 最後,我們以內耳器官體外培養進行耳毒性物質評估。器官體外培養系統不僅便於耳毒性物質大量篩選、有效節省時間經費外,更有利於耳毒性物質劑量反應分析及相關機制建立。我們利用體外培養耳蝸組織證明, 銀杏萃取物EGb761能透過抑制活性氧自由基及一氧化氮生成,降低gentamicin所引起的耳毛細胞自體凋亡比例及減少細胞死亡數目;另外,天竺鼠以口服方式投予EGb761也能減緩gentamicin所引起的耳毒性傷害。實驗同時篩選銀杏葉萃取物內含之活性成分,如槲黃素(quercetin)、白果內酯 (bilobalide)、銀杏內酯A (ginkgolide A)及銀杏內酯B (ginkgolide B)等,證實均有類似功效。 合併本研究所建立的動物實驗系統,將能有效篩檢並分析耳毒性物質,以提供詳細的毒性資料,同時也可評估具潛力可治療內耳疾病的藥物。此外,有鑑於耳石器官的檢查仍存在爭論,此內耳功能檢測系統也提供平台以進行相關的內耳生理及病理研究。 | zh_TW |
dc.description.abstract | Ototoxicity implies the functional impairment of the inner ear or its neural pathway caused by certain substances or insults. As the range of ototoxic agents is diverse and extensive, it is hard to obtain their toxic information without some imprecision. Furthermore, as new drug delivery routes of medication, such as intratympanic delivery, were proposed, the existing toxic data should also be re-visited. The ways to evaluate ototoxicity in the past were mostly limited and inadequate. The main problem is the lack of thorough assessment of function status of the whole inner ear. The inner ear includes the auditory endorgan (the cochlea), and the vestibular endorgans (the utricle, saccule and semicircular canals). Up to date, only the auditory function tests are well established in the animals at most laboratories. On the contrary, vestibular function in the animal is frequently based on behavioral observation. Functional assessment of the inner ear that fails to include every endorgan results in inaccurate information of ototoxicity. In view of these deficits, we aimed to establish a system to completely evaluate inner ear functions in the guinea pigs. The work was divided into four parts and was described here separately.
In the first part, we developed the ocular vestibular evoked myogenic potentials (oVEMP) test in the guinea pigs for the assessment of the utricular function. By gently fixing an alert guinea pig in a clamp, bone-conducted vibration (BCV) was given in the forehead. Normal oVEMP waveform was recorded near the inferior extraocular muscles bilaterally. The response comes from crossed vestibular-ocular reflex (VOR). When one utricle was destroyed by gentamicin, the oVEMP response vanished. We have also developed cervical VEMP (cVEMP) in the guinea pigs to evaluate saccular function. With cVEMP and oVEMP tests, the function of the otolith organs can be investigated. In order to efficiently record VEMPs in the guinea pigs, we applied both air-conducted sound (ACS) and bone-conducted vibration (BCV) to induce cVEMP and oVEMP. Guinea pigs were treated with intratympanic gentamicin in the left ear to induced ototoxicity. Using ACS mode, oVEMPs were absent in all animals despite the stimulus intensity increased up to 120 dB pe SPL. Conversely, using BCV mode, oVEMPs were present on the left (gentamicin-treated side) eye, and absent on the right (control) eye in all 10 (100%) animals. Via ACS mode, all (100%) right (control) neck showed clear cVEMPs, and all left (gentamicin-treated side) neck revealed absent cVEMPs. However, via BCV mode, except all (100%) right (control) neck showed clear cVEMPs, 6 (60%) animals also demonstrated clear cVEMP on the left neck. It appears that ACS mode is unreliable to elicit oVEMPs in guinea pigs, since the prevalence is low. BCV mode is not specific for inducing cVEMPs in guinea pigs, because a crossed response may occur. Thus, appropriate animal models for cVEMP and oVEMP in guinea pigs are via ACS and BCV modes, respectively, which are also consistent with those reported in humans. Next we combined auditory brainstem responses, cVEMP, oVEMP, and the caloric test to establish an inner ear monitoring system in the guinea pigs. Tested on the gentamicin-treated guinea pigs, we demonstrated normal results in all tests at all control ears, while elevated ABR threshold and absent responses in caloric, oVEMP and cVEMP tests were noted in all gentamicin-treated ears. The results of function tests were compatible with the observation of inner ear pathology. Apparently, the inner ear monitoring system including ABR, caloric, oVEMP and cVEMP tests helps to evaluate toxicity of agents on the inner ear of guinea pigs. Last, we use in vitro organotypic culture of inner ear endorgans to evaluate ototoxicity. For screening purpose, using organ culture has the advantages of time- and cost-saving and demonstration of dose response relationship. It is also a proper medium for the research of ototoxic mechanism. We showed that EGb761 (a standardized preparation of the extract of Ginkgo Biloba) reduced gentamicin-induced elevation of reactive oxygen species (ROS) and nitric oxide (NO) in cochlear cultures from postnatal rats. EGb761 also inhibited gentamicin-induced cellular apoptosis and reduced hair cell loss. In guinea pigs, EGb761feeding prevented gentamicin-induced cochleotoxicity. In the cochlear culture, EGb761 components quercetin, bilobalide, ginkgolide-A, and ginkgolide-B, but not kaempferol, significantly prevented the gentamicin-induced hair cell damage. The test battery in the animal model proves to be useful to screen and assess ototoxic drugs and to test potential therapeutic agents in the inner ear disorders. Moreover, the animal model provides a platform for the research to elucidate the controversy on the origin of VEMP tests and further studies on the inner ear. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T05:01:30Z (GMT). No. of bitstreams: 1 ntu-99-D93447004-1.pdf: 6390798 bytes, checksum: cba01a5787974dd88ac11bd793e31d6c (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 口試委員會審定書 I
誌謝 II 中文摘要 III ABSTRACT V LIST OF ABBREVIATION VII I. INTRODUCTION 1 1.1 THE INNER EAR 1 1.1.1 The cochlea 1 1.1.2 The otolith organs 2 1.1.3 The semicircular canals 4 1.2 OTOTOXICITY 4 1.2.1 Mechanism of ototoxicity 5 1.2.2 Attenuation of ototoxicity and the possible role of extract of Gingko Biloba 6 1.2.3 Intratympanic delivery of medication 7 1.3 EVALUATION OF OTOTOXICITY 10 1.3.1 Auditory function tests 10 1.3.2 Vestibular function test 11 1.3.3 Evaluation of ototoxicity in the animal 12 1.4 THE AIM AND DESIGN OF THE STUDY 14 II. MATERIALS AND METHODS 16 2.1 ANIMAL PREPARATION 16 2.2 APPLICATION OF EARDROPS 16 2.3 AUDITORY BRAINSTEM RESPONSES (ABR) 17 2.4 VESTIBULAR EVOKED MYOGENIC POTENTIALS (VEMPS) 17 2.4.1 Ocular vestibular evoked myogenic potentials (oVEMP) test 17 2.4.2 Cervical vestibular evoked myogenic potentials (cVEMP) test 19 2.4.3 Air-conducted sound (ACS) stimulation for oVEMP and cVEMP 20 2.4.4 Bone-conducted vibration (BCV) stimulation for oVEMP and cVEMP 20 2.5 CALORIC TEST 21 2.6 MORPHOLOGICAL STUDY ON THE SENSORY EPITHELIUM OF THE INNER EAR ENDORGANS FROM GUINEA PIGS 21 2.7 INDUCTION OF GENTAMICIN TOXICITY ON ORGANOTYPIC CULTURES OF COCHLEAE FROM POSTNATAL RATS 22 2.8 TREATMENT OF THE ACTIVE CONSTITUENTS OF EGB761 IN COCHLEAR CULTURE 23 2.9 HAIR CELL STAINING AND COUNTING IN THE ORGANOTYPIC CULTURE OF THE COCHLEA 23 2.10 TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE-MEDIATED DUTP NICK END LABELING (TUNEL) 24 2.11 MEASUREMENT OF ROS IN THE COCHLEA OF ORGANOTYPIC CULTURE 25 2.12 MEASUREMENT OF NO IN THE COCHLEA OF ORGANOTYPIC CULTURE 26 2.13 STATISTICAL METHODS 26 III. RESULTS 28 3.1 THE DEVELOPMENT OF OVEMP TEST IN THE GUINEA PIGS FOR THE EVALUATION OF UTRICULAR FUNCTION 28 3.1.1 oVEMPs in healthy guinea pigs 28 3.1.2 oVEMPs in guinea pigs under general anesthesia 28 3.1.3 oVEMPs in gentamicin-treated guinea pigs 29 3.1.4 Morphological study of the utricle 29 3.2 THE OPTIMAL STIMULATION OF OVEMP AND CVEMP TESTS IN THE GUINEA PIGS 30 3.2.1 oVEMPs: ACS versus BCV modes 30 3.2.2 cVEMPs: ACS versus BCV modes 31 3.2.3 Morphological study 31 3.3 A NOVEL INNER EAR MONITORING SYSTEM IN THE GUINEA PIGS 32 3.3.1 Cochlear part 32 3.3.2 Vestibular part 32 3.4 EVALUATION OF GENTAMICIN-INDUCED OTOTOXICITY IN ORGANOTYPIC COCHLEAR CULTURE AND THE EFFECT OF EGB761 33 3.4.1 In vitro study in rat cochlear cultures: Gentamicin-induced hair cell damage 33 3.4.2 In vitro study in rat cochlear cultures: Effect of EGb761 on gentamicin cytotoxicity and apoptosis 34 3.4.3 In vitro study in rat cochlear cultures: Effect of active constituents of EGb761 on gentamicin cochleotoxicity 34 3.4.4 In vitro study in rat cochlear cultures: EGb761 reduced gentamicin-induced ROS and NO production 35 3.4.5 In vivo study in guinea pigs: Auditory function and hair cell damage in the gentamicin and/or EGb761 groups 35 IV. DISCUSSION 37 4.1 THE DEVELOPMENT OF OVEMP TEST IN THE GUINEA PIGS FOR THE EVALUATION OF UTRICULAR FUNCTION 37 4.2 THE OPTIMAL STIMULATION OF OVEMP AND CVEMP TESTS IN THE GUINEA PIGS 40 4.3 A NOVEL INNER EAR MONITORING SYSTEM FOR EVALUATION OF OTOTOXICITY 43 4.4 EVALUATION OF GENTAMICIN-INDUCED OTOTOXICITY IN ORGANOTYPIC COCHLEAR CULTURE AND THE EFFECT OF EGB761 44 V. SUMMARY AND PROSPECTIVE 48 REFERENCES 50 附錄 91 AN ANIMAL MODEL OF OCULAR VESTIBULAR-EVOKED MYOGENIC POTENTIAL IN GUINEA PIGS EVALUATION OF GUINEA PIG MODEL FOR OCULAR AND CERVICAL VESTIBULAR-EVOKED MYOGENIC POTENTIALS FOR VESTIBULAR FUNCTION TEST A NOVEL INNER EAR MONITORING SYSTEM FOR EVALUATING OTOTOXICITY OF GENTAMICIN EARDROPS IN GUINEA PIGS EGB761 (GINKGO BILOBA) PROTECTS COCHLEAR HAIR CELLS AGAINST OTOTOXICITY INDUCED BY GENTAMICIN VIA REDUCING REACTIVE OXYGEN SPECIES AND NITRIC OXIDE-RELATED APOPTOSIS | |
dc.language.iso | en | |
dc.title | 以動物內耳功能檢測系統進行耳毒性評估之研究 | zh_TW |
dc.title | Investigation of ototoxicity using inner ear monitoring system in the animal | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 楊怡和,林仁混,楊榮森,蕭水銀 | |
dc.subject.keyword | 耳毒性,天竺鼠,前庭功能,前庭誘發肌性電位,銀杏萃取物,器官培養, | zh_TW |
dc.subject.keyword | ototoxicity,guinea pigs,vestibular function,VEMP,extract of Ginkgo Biloba,organotypic culture, | en |
dc.relation.page | 91 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2010-11-24 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 毒理學研究所 | zh_TW |
顯示於系所單位: | 毒理學研究所 |
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