Aminoglycosides (AG) are commonly prescribed antibiotics with potent bactericidal activities. One main side effect is permanent sensorineural hearing loss, induced by selective inner ear sensory hair cell death. Much work has focused on AG's initiating cell death processes, however, fewer studies exist defining mechanisms of AG uptake by hair cells. The current study investigated two proposed mechanisms of AG transport in mammalian hair cells: mechanotransducer (MET) channels and endocytosis. To study these two mechanisms, rat cochlear explants were cultured as whole organs in gentamicin-containing media. Two-photon imaging of Texas Red conjugated gentamicin (GTTR) uptake into live hair cells was rapid and selective. Hypocalcemia, which increases the open probability of MET channels, increased AG entry into hair cells. Three blockers of MET channels (curare, quinine, and amiloride) significantly reduced GTTR uptake, whereas the endocytosis inhibitor concanavalin A did not. Dynosore quenched the fluorescence of GTTR and could not be tested. Pharmacologic blockade of MET channels with curare or quinine, but not concanavalin A or dynosore, prevented hair cell loss when challenged with gentamicin for up to 96 hours. Taken together, data indicate that the patency of MET channels mediated AG entry into hair cells and its toxicity. Results suggest that limiting permeation of AGs through MET channel or preventing their entry into endolymph are potential therapeutic targets for preventing hair cell death and hearing loss.

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ORAL PRESENTATIONSdecompression surgery are low risk of hearing impediment and long effective period after onset of paralysis.Objective: Test the hypothesis that open mechanotransducer (MET) channels are required for aminoglycoside entry and toxicity in auditory hair cells.Method: Cochlear cultures from postnatal 4-day-old rats were treated with gentamicin with and without MET channel blockers. The effects of MET channel blockers on hair cell survival were assessed by cell counts after immunohistochemistry. Two-photon imaging was used to quantify uptake of TexasRed-conjugated gentamicin (GTTR) into live hair cells.Results: Gentamicinalone (0.1mM) caused 76.5% hair cell loss in the basal cochlear turn. Cotreatment with MET channel blockers, 1.0 mM curare, and 0.5 mM quinine conferred protection (0.4% and 7.4% hair cell loss, both P < .001); whereas treatment with endocytosis inhibitors, 2.6 µM conconavalin A and 80 µM dynosore, did not (63.7% and 76.0% hair cell loss). Two-photon imaging showed that GTTR uptake (3 µM) into live hair cells was rapid and selective. Quinine and curare, but not concanavalin A, reduced GTTR uptake. Furthermore, as low calcium increases the open probability of MET channels, hypocalcemia showed facilitated GTTR uptake.Conclusion: Functional MET channels are required for aminoglycoside uptake into hair cells and its toxicity. Results suggest that limiting permeation of aminoglycosides through MET channels is a potential therapeutic target for preventing hair cell death. Otology/Neurotology Habituation following Tinnitus Retraining Therapy in Tinnitus SufferersJiun Fong Thong (presenter); Mei Ching Wong; S. Junaidah; Yew Meng Chan, FRCS Objective: Evaluate the efficacy of Tinnitus Retraining Therapy (TRT) in habituating patients with tinnitus.Method: Prospective study of patients presenting to the tinnitus clinic at a tertiary referral otorhinolaryngology unit in Singapore over a 13-year period (1997 to 2010). Patients who underwent Tinnitus Retraining therapy were followed up with structured interviews with the aid of questionnaire forms. Habituation following TRT was evaluated.Results: A total of 702 patients were studied (55% male, 45% female). Average age was 51 years. Habituation of reaction to tinnitus and habituation of perception were analyzed. Average duration of follow-up was 33 months (range, 0.25-151 months). A total of 68% of patients described improvement in annoyance following TRT. Of these, 80% described habituation of perception as well. There was no statistical difference in gender and age between patients who did and did not respond to TRT. However, duration of treatment was significantly longer in patients who habituated. Conclusion:The goal of TRT is to achieve habituation of reaction to tinnitus. Habituation of perception is often a secondary result of sufficiently habituated response. From our study, more than two-thirds of patients with tinnitus achieved habituation of reaction, and of these, the majority also habituated to awareness of the tinnitus. Otology/Neuroto...

BackgroundSensitization to inhaled allergens in children with bronchial asthma significantly affects asthma pathogenesis, severity and persistence into late childhood and adulthood. The present study determined the prevalence of sensitization to inhaled allergens in children with bronchial asthma and wheezing episodes in order to investigate the effect of positive sensitization on the severity and control of asthma symptoms and to screen for other associated allergic conditions.MethodsA cross-sectional study was conducted, including children between 6 months and 14 years of age attending the chest clinic of Al-Karak, south of Jordan, between November 2013 and February 2016. Skin prick tests (SPTs) using 11 standardized allergen extracts were conducted in 277 children. The severity of asthma was determined based on the Global Initiative for Asthma (GINA) assessment and the Childhood Asthma Control Test (C-ACT) in addition to the history of use of systemic steroids and hospital admissions within the past 12 months.ResultsSixty-seven percent of children with bronchial asthma reported sensitization to one or more of the inhaled allergens. The most common allergens were olive pollens (18%), cat fur (13.5%), and Dermatophagoides pteronyssinus (11.9%). There was a significant increase in allergen sensitization with age (p < 0.001). The most common concomitant allergic condition among children was allergic rhinitis (71.5%); however, allergic conjunctivitis was the only allergic condition that correlated with the skin test reactivity (p = 0.01). A family history of bronchial asthma was confirmed in 40.4% of children. Children with positive SPTs had lower ACT scores and reported more frequent use of systemic steroids and admissions to hospital within the past 12 months; however, this effect was not statistically significant (p > 0.05).ConclusionsSensitization to inhaled allergens is highly prevalent in children with asthma and wheezing episodes in southern Jordan and may be correlated with the severity of the disease. Therefore, appropriate measures to recognize and avoid these allergens are highly recommended. Most children in our study suffered from concomitant allergic rhinitis, indicating that an appropriate diagnosis and treatment of allergic rhinitis could significantly improve asthma control and thus the quality of life of these children.Trial registrationThis study is not a clinical trial.