Berberine chloride protects cochlear hair cells from aminoglycoside-induced ototoxicity by reducing the accumulation of mitochondrial reactive oxygen species.

Aminoglycoside, a medicinal category of antibiotics, are used in treatment of Gram-negative bacterial infections. Although they are the most widely-used antibiotics due to their high efficacy and low cost, several main adverse effects have been reported including nephrotoxicity and ototoxicity. Since drug-induced ototoxicity is one of the major etiological causes of acquired hearing loss, we examined cochlear hair cell damages caused by three aminoglycosides (amikacin, kanamycin, and gentamicin), and investigated protective property of an isoquinoline-type alkaloid, Berberine chloride (BC). Berberine, a well-known bioactive compound found from medicinal plants, has been known to have anti-inflammatory, antimicrobial effects. To determine protective effect of BC in aminoglycoside-induced ototoxicity, hair cell damages in aminoglycoside- and/or BC-treated hair cells using ex vivo organotypic culture system of mouse cochlea. Mitochondrial ROS levels and depolarization of mitochondrial membrane potential were analyzed, and TUNEL assay and immunostaining of cleaved caspase-3 were performed to detect apoptosis signals. As the results, it was found that BC significantly prevented aminoglycoside-induced hair cell loss and stereocilia degeneration by inhibiting excessive accumulation of mitochondrial ROS and subsequent loss of mitochondrial membrane potential. It eventually inhibited DNA fragmentation and caspase-3 activation, which were significant for all three aminoglycosides. This study is the first report suggested the preventative effect of BC against aminoglycoside-induced ototoxicity. Our data also suggests a possibility that BC has the potential to exert a protective effect against ototoxicity caused by various ototoxic drugs leading to cellular oxidative stress, not limited to aminoglycoside antibiotics.

A tri-coil bellows-type round window transducer with improved frequency characteristics for middle-ear implants.

A number of methods to drive the round window (RW) using a floating mass transducer (FMT) have been reported. This method has attracted attention because the FMT is relatively easy to implant in the RW niche. However, the use of an FMT to drive the RW has been proven to produce low outputs at frequencies below approximately 1 kHz. In this study, a new tri-coil bellows-type transducer (TCBT), which has excellent low frequency output and is easy to implant, is proposed. To design the frequency characteristics of the TCBT, mechanical and electrical simulations were performed, and then a comparative analysis was conducted between a floating mass type transducer (like the FMT) and a fixed type transducer (like the TCBT). The features of the proposed TCBT are as follows. First, the TCBT's housing is fixed to the RW niche so that it does not vibrate. Second, the internal end of a tiny bellows is connected to a vibrating three-pole permanent magnet located within three field coils. Finally, the rim of the bellows bottom is attached to the end of the housing that hermetically encloses the three field coils. In this design, the only vibrating element is the bellows itself, which efficiently drives the RW membrane. To evaluate the characteristics of this newly developed TCBT, the transducer was installed in the RW niche of temporal bones and the velocity of the stapes was measured using a laser Doppler vibrometer. The experimental results indicate that the TCBT can produce 100, 111, and 129 dB SPL equivalent pressure outputs at below 1 kHz, 1-3 kHz, and above 3 kHz, respectively. Thus, the TCBT with one side coupled to the RW via a bellows will be easy to implant and offer better performance than an FMT.

Association Between HbA1c Level and Hearing Impairment in a Nondiabetic Adult Population.

BACKGROUND: The aim of this study was to investigate whether glycosylated hemoglobin (HbA1c) level in nondiabetic patients is associated with hearing impairment in the general Korean population. PATIENTS AND METHODS: Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded from this study for the following reasons: they could not provide data regarding pure tone audiometry, they had ear disease, they had brain disorders, asymmetric sensory neural hearing loss (HL), or they were younger than 40 years or had diabetes mellitus. Finally, 7449 participants were included in this study. RESULTS: The mean HbA1c levels in the low, middle, and high tertiles were 5.3% ± 0.2%, 5.7% ± 0.1%, and 6.1% ± 0.2%, respectively. The numbers of participants in the low, middle, and high tertiles were 2808, 2509, and 2132, respectively. The low-frequency, mid-frequency, high-frequency, and average hearing thresholds were significantly increased with increasing HbA1c tertile. Linear regression analyses showed that HbA1c level in the nondiabetic participants was associated with components of metabolic syndrome. The mean numbers of metabolic syndrome components in the low, middle, and high HbA1c tertiles were 1.22, 1.53, and 2.02, respectively. The participants in the middle and high HbA1c tertiles had a 1.239- and 1.253-fold increased risk of HL, respectively, compared with those in the low HbA1c tertile. CONCLUSION: HbA1c level was associated with hearing impairment in the nondiabetic participants of this study. Therefore, the participants with high HbA1c levels should be closely monitored for hearing impairment.

Comparison of auditory responses determined by acoustic stimulation and by mechanical round window stimulation at equivalent stapes velocities.

Active middle ear implants (AMEIs) have been studied to overcome the limitations of conventional hearing aids such as howling, occlusion, and social discrimination. AMEIs usually drive the oval window (OW) by means of transmitting vibrational force through the ossicles and the vibrational force corresponding to sound is generated from a mechanical actuator. Recently, round window (RW) stimulation using an AMEI such as a floating mass transducer (FMT) to deliver sound to the cochlea has been introduced and hearing improvement in clinical use has been reported. Although previous studies demonstrated that the auditory response to RW stimulation was comparable to a sound-evoked auditory response, few studies have investigated the quantification of the physiologic performance of an AMEI through RW stimulation on the inner ear in vivo. There is no established relationship between the cochlear responses and mechanical stimulation to RW. The aim of this study is to assess the physiologic response in RW stimulation by an AMEI. The transferred energy through the RW to the inner ear could estimate the response corresponding to acoustic stimulation in order to quantify the AMEI output in the ossicular chain or OW stimulation. The parameters of the auditory brainstem responses (ABRs) were measured and compared based on stapes velocities similar enough to be regarded as the same for acoustic stimulation to the external auditory canal (EAC) and mechanical stimulation to the RW in an in vivo system. In conclusion, this study showed that the amplitudes and latencies of the ABRs of acoustic and RW stimulation showed significant differences at comparable stapes velocities in an in vivo system. These differences in the ABR amplitudes and latencies reflect different output functions of the cochlea in response to different stimulation pathways. Therefore, it is necessary to develop a new method for quantifying the output of the cochlea in the case of RW stimulation.