Functional Hair Cell Mechanotransducer Channels Are Required for Aminoglycoside Ototoxicity

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

Presentation of Idiopathic Intracranial Hypertension with Sensorineural Hearing Loss

Objectives: To determine the sensorineural hearing loss (SNHL) pattern in patients with idiopathic intracranial hypertension (IIH). Study Design: Retrospective chart review. Methods: A review of patients with IIH diagnosis and available audiograms. Otologic complaints, hearing threshold and opening pressures were documented before and after intervention. Correlations between opening pressure and hearing thresholds were analyzed using Spearman\u27s rank correlation coefficient due to the non-parametric nature of our data. Results: Forty two patients (mean age = 42.4) were included in the study, 35(83%) of whom were female. The most common otologic symptoms reported were tinnitus in 24 (57%, 14 pulsatile and 10 non-pulsatile), aural fullness in 13 (31%), vertigo in 4 (10%), and facial spasms in 3 (7%) patients. Twenty-nine patients (69%) had some form of hearing loss (threshold over 20dB) of which 17 (40%) were bilateral. The hearing ranged from normal to profound hearing loss, and no specific pattern (low, central, high frequency or flat) was statistically significant in unilateral or bilateral patients. Two patients presented with sudden SNHL and four had normal retinal examination. In three patients hearing thresholds improved with treatment. There was no statistically significant correlation between opening pressures and hearing thresholds, except for air conduction on the left ear (p=0.0059). Conclusions: IIH does not present with any pattern of hearing loss and may present as unilateral, bilateral, mild to profound or even as sudden SNHL

Hold the Salt: History of Salt Restriction as a First-line Therapy for Menière\u27s Disease

Objectives:To determine the historical origins of the usage of the salt restriction diet as an intervention for Menière\u27s disease (MD).Methods:Articles on MD and salt restriction were identified using Pubmed and Google scholar. Original manuscripts from 19th and 20th century as well as selected otological textbooks in English, German, and French were also reviewed.Results:The oldest recommendation of salt restriction in the literature was by Dederding (1889-1955) in 1929. She and her mentor, Sydney Holger Mygind (1884-1970), believed MD was caused by dysfunctional water metabolism. In several published manuscripts, they proposed that a reduced salt and fluid diet was an effective treatment for MD. Their contemporaries supported their findings, most notably, Albert C. Furstenberg (1890-1969) who suggested salt restriction alone as treatment for MD. Furstenberg, in his initial study implementing salt restriction in 15 patients with MD and then in a larger study with 150 patients, was the first to produce results that supported salt restriction as therapy for MD. It was not until 1980, when LB Jongkees first published his criticism of this treatment, that salt restriction was questioned. Since then, numerous published articles have been critical of salt restriction therapy and skeptical of its initial adoption into clinical practice.Conclusions:Since Dederding\u27s and Mygind\u27s publications in 1929 and Furstenberg\u27s trial in 1934, the salt restriction diet has remained a primary first-line treatment for MD. Since the 1950s, various publications have both supported and argued this treatment, and the evidence of its validity remains inconclusive