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  • 1. Grondin, Yohann
    et al.
    Cotanche, Douglas A
    Manneberg, Otto
    Molina, Ramon
    Treviño-Villarreal, J Humberto
    Sepulveda, Rosalinda
    Clifford, Royce
    Bortoni, Magda E
    Forsberg, Scott
    Labrecque, Brian
    Altshul, Larisa
    Brain, Joseph D
    Jackson, Ronald L
    Rogers, Rick A
    Pulmonary delivery of d-methionine is associated with an increase in ALCAR and glutathione in cochlear fluids.2013In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 298, p. 93-103Article in journal (Refereed)
    Abstract [en]

    In animals, hearing loss resulting from cochlear mechanosensory cell damage can be mitigated by antioxidants such as d-methionine (d-met) and acetyl-l-carnitine (ALCAR). The systemic routes of administration of these compounds, that must of necessity transit trough the cochlear fluids, may affect the antioxidant levels in the cochlea and the resulting oto-protective effect. In this study, we analyzed the pharmacokinetics of [C]d-met in the cochlea and four other tissues after intratracheal (IT), intranasal (IN), and oral by gavage (OG) administration and compared it to intravenous administration (IV). We then analyzed the effect of these four routes on the antioxidant content of the cochlear fluids after d-met or ALCAR administration, by liquid chromatography/mass spectrometry. Our results showed that the concentration of methionine and ALCAR in cochlear fluids significantly increased after their respective systemic administration. Interestingly, d-met administration also contributed to an increase of ALCAR. Our results also showed that the delivery routes differently affected the bioavailability of administered [C]d-met as well as the concentrations of methionine, ALCAR and the ratio of oxidized to reduced glutathione. Overall, pulmonary delivery via IT administration achieved high concentrations of methionine, ALCAR, and oxidative-related metabolites in cochlear fluids, in some cases surpassing IV administration, while IN route appeared to be the least efficacious. To our knowledge, this is the first report of the direct measurements of antioxidant levels in cochlear fluids after their systemic administration. This report also demonstrates the validity of the pulmonary administration of antioxidants and highlights the different contributions of d-met and ALCAR allowing to further investigate their impact on oxidative stress in the cochlear microenvironment.

  • 2. Nilsson, Mats E.
    et al.
    Schenkman, Bo N.
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH. Université Catholique de Louvain, Belgium.
    Blind people are more sensitive than sighted people to binaural sound-location cues, particularly inter-aural level differences2016In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 332, p. 223-232Article in journal (Refereed)
    Abstract [en]

    Blind people use auditory information to locate sound sources and sound-reflecting objects (echolocation). Sound source localization benefits from the hearing system's ability to suppress distracting sound reflections, whereas echolocation would benefit from "unsuppressing" these reflections. To clarify how these potentially conflicting aspects of spatial hearing interact in blind versus sighted listeners, we measured discrimination thresholds for two binaural location cues: inter-aural level differences (ILDs) and inter-aural time differences (ITDs). The ILDs or ITDs were present in single clicks, in the leading component of click pairs, or in the lagging component of click pairs, exploiting processes related to both sound source localization and echolocation. We tested 23 blind (mean age = 54 y), 23 sighted-age matched (mean age = 54 y), and 42 sighted-young (mean age = 26 y) listeners. The results suggested greater ILD sensitivity for blind than for sighted listeners. The blind group's superiority was particularly evident for ILD-lag-click discrimination, suggesting not only enhanced ILD sensitivity in general but also increased ability to unsuppress lagging clicks. This may be related to the blind person's experience of localizing reflected sounds, for which ILDs may be more efficient than ITDs. On the ITD-discrimination tasks, the blind listeners performed better than the sighted age-matched listeners, but not better than the sighted young listeners. ITD sensitivity declines with age, and the equal performance of the blind listeners compared to a group of substantially younger listeners is consistent with the notion that blind people's experience may offset age-related decline in ITD sensitivity.

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