Introduction: Radiotherapy can cause permanent hearing loss when the ears are included in the radiation field. To date, no treatment is available to prevent this outcome. The effects of radiation are caused by free radical formation, leading to apoptosis of the cells in the organ of Corti. Metformin has demonstrated anticancer and anti-aging properties through the regulation of reactive oxygen species production after cellular stresses.Objectives: To determine the safety and radio-protective properties of Metformin against radiation-induced cochlear damage in vivo and in vitro. Materials and Methods: For the in vitro study, cultured auditory hair cells (HEI-OC1) were exposed to different concentrations of Metformin to determine its safety. Next, cells were incubated with these concentrations and subjected to radiation. Cell viability after experiments was determined with the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay.For the in-vivo study, 15 guinea pigs were divided in two groups: drinking tap water (n=7) and drinking water containing Metformin (n=8) at a dose of 100 mg/kg/day. The ears of the animals were unilaterally irradiated for 20 days (total dose 71 Gy) and subsequently divided in four groups: Control (n=7), Irradiated (n=7), Metformin (n=8), Experimental (n=8). Distortion Products Otoacoustic Emissions (DPOAE) and Auditory Brainstem Responses (ABR) were assessed before, one week and six weeks after completion of radiotherapy.Results: Metformin was not ototoxic or radio-protective in cultured auditory hair cells. DPOAE measurements did not show hearing loss or differences between the four groups at the different time points evaluated. After 6 weeks, ABR demonstrated progressive hearing loss. Experimental ears had less hearing loss than radiated ones; however, differences were not statistically significant.Conclusion: Metformin is not ototoxic in vitro or in vivo. Metformin was not protective against radiation induced cell death in vitro. / Introduction: La radiothérapie peut provoquer une perte auditive permanente quand l'oreille est incluse dans la zone de radiation. Il n'y existe aucun traitement préventif pour cet effet néfaste. La radiation provoque la formation des radicales libres entrainant la mort de cellules dans l'organe de Corti. La Metformine, un médicament vastement utilisé dans le traitement du diabète a montré des propriétés anticancéreuses et antivieillissement par la régulation de la production d'espèces réactives de l'oxygène après le stress cellulaire. Objectifs: Déterminer l'ototoxicité et les propriétés radio-protectives de la Metformine contre l'atteinte cochléaire provoqué par radiation in vivo et in vitro.Matériaux et méthodes: Les cellules auditives cultivées (HEI-OC1) ont été exposées à différentes concentrations de Metformine pour déterminer le potentiel d'ototoxicité de ce dernier. En plus, les cellules ont été incubées avec diverses concentrations et par la suite, exposées à la radiation. La survie cellulaire a été déterminée par la méthode MTS. Quinze cochon d'Inde ont été divisés en deux groupes: buvant de l'eau potable (n=7) et buvant de l'eau contenant la Metformine (n=8) avec une dose de 100 mg /kg/jour. Les oreilles des animaux ont été irradiées unilatéralement pendant 20 jours (dose totale 71 Gy) et par conséquence ont été divisées en quatre groupes: Control (n=7), Irradiées (n=7), Metformine (n=8), Expérimentales (n=8). Les Produits de Distorsion des Émissions Otoacoustiques (PDEO) et les Réponses Auditives du Tronc Cérébral (RATC) ont été six semaines après la radiothérapie.Résultats: La Metformine n'est pas été ototoxique ou radio-protective des cellules auditives cultivées. Les PDEO test n'ont pas montré de perte auditive ou de différences entre les quatre groupes aux différents temps évaluées. Après six semaines. Les oreilles expérimentales ont eu moins de perte auditive comparées aux oreilles irradiées, néanmoins les différences n'ont pas été significatives.Conclusion: La Metformine n'est pas ototoxique in vitro ou in vivo. La Metformine n'a pas été otoprotective in vitro ou contre la perte auditive causée par radiation après un suivi de six semaines après la fin de la radiothérapie.

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<p> The goal of this study was to determine whether sequentially acquired bilateral implants provide improved speech understanding relative to performance with unilateral implants in varying sound source configurations that may more closely represent daily listening environments. Participants were divided into higher and lower performance groups based upon their best unilateral performance on monosyllabic words in quiet and asked to repeat Bamford-Kowal-Bench Speech-in-Noise (BKB-SIN) sentences in unilateral and bilateral listening conditions. The sentences were always presented from directly in front, while competing noise was presented from varying locations. Results indicated that the bilateral listening condition yielded significantly better scores compared to the unilateral listening condition across all participants, with the higher performance group's scores significantly better than for the lower performance group. Both groups had similar gains in performance. No significant differences were observed amongst sound sources, contrary to the original hypothesis. Among demographic variables, only unilateral performance on words in quiet and onset of deafness were highly correlated with bilateral performance. As the initial grouping variable addressed performance in quiet, a second analysis regrouped participants by onset of deafness (pre- vs. postlingual) This regrouping yielded even greater group differences overall, and some noise configurations were now significantly different for the postlingually deafened participants. Taken together, these results suggest that postlingually deafened participants may be able to use higher level binaural processes established prior to deafness and not available to prelingually deafened listeners.</p>

Nine tympanometric measures were examined in 68 normal ears and 14 ears with surgically confirmed otosclerosis. Two parameters, static admittance and tympanometric width, were derived from standard low frequency tympanometry and two parameters, resonant frequency and frequency corresponding to admittance phase angle of 45$ sp circ$ (F45$ sp circ),$ were derived from multifrequency, multicomponent tympanometry. The results show the advantage of multifrequency, multicomponent tympanometry over standard low frequency tympanometry in differentiating otosclerotic ears from normal ears. In particular, for identifying high impedance pathologies, the present findings support the use of sweep frequency (SF) recording for measuring resonant frequency and frequency corresponding to admittance phase angle of 45$ sp circ$ (F45$ sp circ)$ and positive tail compensation for measuring resonant frequency. The relationship among the measures obtained in this study also revealed that two distinct signs are evident in the patient group; (1) an increase in the stiffness of the middle ear best shown by F45$ sp circ$ measured using SF method, and (2) an increase in the sharpness of the tympanogram best shown by tympanometric width. The combination of F45$ sp circ$ measured using SF method and tympanometric width separated normal from otosclerotic ears better than any single measure used in this study.

Cisplatin is an extensively used chemotherapeutic agent in the treatment of a broad spectrum of tumors. Ototoxicity is currently the most frequent dose limiting side-effect of cisplatinum chemotherapy. Ototoxicity has been shown to be the result of two mechanisms: oxidation, and more recently: inflammation. Various agents have been studied to prevent cisplatin ototoxicity. None has been proven effective in clinical trials to this date. Curcumin, a spice derived from a plant called Curcuma longa, possesses antioxidant activity and inhibits mediators of inflammation. However, curcumin low solubility in water and its low bioavailability limit its use. These issues can be solved using a novel technique called nano-encapsulation. In this research project, we wanted to find out whether curcumin could be nano-encapsulated, and, if so, whether the nano-encapsulated curcumin applied transtympanically is ototoxic, and whether it could be detected in the cochlear fluid and the blood. To answer these questions, a polymer of N-isopropylacrylamide (NIPAM), N-vinyl-2-pyrrolidone (VP), Poly(ethyleneglycol) monoacrylate (PEG-A) was formed. Curcumin was then mounted in this polymer. Different measurements were performed to characterize the created molecule such as the fourier transform infrared (FTIR) spectroscopy, the ultraviolet visible (UV-Vis) spectroscopy, and the atomic force microscopy (AFM). Results showed that curcumin was indeed nano-encapsulated. To test the safety of the nano-encapsulated curcumin, it was applied transtympanically to the ears of 5 chinchillas. The hearing was recorded using the auditory brainstem response (ABR) and the distortion product otoacoustic emission (DPOAE). Results of this pilot study showed that the nano-encapsulated curcumin is not ototoxic. To detect the presence of the nano-encapsulated curcumin in the cochlear fluid and the blood, it was applied transtympanically to chinchillas. The cochlear fluids and the blood samples were withdrawn / La cisplatine est un agent chimiothérapeutique largement utilisé dans le traitement d'un vaste éventail de tumeurs. L'ototoxicité est actuellement l'effet secondaire le plus important limitant l'utilisation de la cisplatine. L'ototoxicité résulte de deux mécanismes connus soit : l'oxidation, et plus récemment: l'inflammation. Plusieurs agents ont été étudiés pour éviter l'ototoxicité de la cisplatine. Jusqu'à ce jour, aucun n'a été prouvé efficace en clinique. La curcumine, une épice tirée d'une plante appelée Curcuma longa, possède une activité anti-oxidante et inhibe les médiateurs de l'inflammation. Toutefois, la faible solubilité de la curcumine dans l'eau et sa faible biodisponibilité limite son utilisation. Ces deux problèmes peuvent être résolus en utilisant une nouvelle technique appelée la nano-encapsulation. Dans ce projet de recherche, nous voulions déterminer si la curcumine pourrait être nano-encapsulée, et, si oui, si la curcumine nano-encapsulée appliquée à travers le tympan serait ototoxique, et si elle pourrait être décelée dans le liquide cochléaire et le sang. Pour répondre à ces questions, un polymère de N-isopropylacrylamide (NIPAM), N-vinyl-2-pyrrolidone (VP), et de poly (éthylène glycol) monoacrylate (PEG-A) a été formé. La curcumine a été ensuite incorporée dans ce polymère. Différentes mesures ont été réalisées pour caractériser la molécule créée comme la spectroscopie infrarouge à transformée de fourier (IRTF), la spectroscopie ultraviolet visible (UV-Vis) et la microscopie à force atomique (AFM). Les résultats ont montré que la curcumine a été effectivement nano-encapsulée. Pour tester la sécurité de la curcumine nano-encapsulée, une application transtympanique a été délivrée aux oreilles moyennes de 5 chinchillas. L'audition a été mesurée en utilisant la réponse auditive du tronc cérébral (RAT) et les émissions oto-acoustiques évoquées par produit$

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 68-02, Section: B, page: 0868. Adviser: Ron Chambers. Includes bibliographical references (leaves 77-91) Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph.D.)--The University of Iowa, 2006. / (UMI)AAI3225660. Adviser: Richard S. Tyler. Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3673.

Thesis (Ed. D.)--West Virginia University, 2009. / Title from document title page. Document formatted into pages; contains x, 152 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 94-99).

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008. / Source: Dissertation Abstracts International, Volume: 69-05, Section: B, page: 2885. Adviser: David M. Gooler. Includes bibliographical references (leaves 103-108) Available on microfilm from Pro Quest Information and Learning.