Safety and efficacy of preauricular fistulectomy with fascia-anchoring suture technique: A large case series.

OBJECTIVE: This study aimed to analyze the safety and efficacy of preauricular fistulectomy with fascia-anchoring suture technique through large case series. In addition, differences in surgical outcomes according to preoperative status and age were investigated. METHODS: In this retrospective study, 380 patients (450 ears) with preauricular fistula (PAF) who underwent preauricular fistulectomy with fascia-anchoring suture technique by a single surgeon (E.P) were enrolled. Patients were divided into fresh, previous incision and drainage (I&D), and the revision surgery groups according to the preoperative status. Additionally, they were divided into adult and pediatric groups according to age. Patient's demographics, postoperative infections, and recurrence rates were analyzed. RESULTS: The mean age of the patients was 28.3 years, and there were 119 males and 261 females. Out of 450 PAFs (n = 281 in the fresh groups, n = 119 in the previous I&D groups, and n = 50 in the revision groups), 21 (4.7 %) cases had postoperative infections and 12 (2.7 %) cases had recurrence. There was no difference in postoperative infections, regardless of the preoperative condition (I&D group, p = 0.701; revision group, p = 0.658). The recurrence rate was higher in the revision group than in the fresh and I&D groups (p = 0.004). There was no significant difference in postoperative infection (p = 0.221) or recurrence (p = 0.161) between adults and children. CONCLUSIONS: The study found that performing preauricular fistulectomy with a fascia-anchoring suture technique led to low rates of postoperative infections and recurrences. These positive outcomes were consistent across different patient groups categorized by preoperative status and age, indicating the technique's safety and effectiveness for all patients with preauricular fistulas.

Dynamic Range and Neural Response Threshold in Cochlear Implant Mapping Can Be Useful in Predicting Prognosis Related to Postoperative Speech Perception.

BACKGROUND AND OBJECTIVES: To analyze mapping changes in dynamic range (DR) and neural response threshold (NRT) as prognostic factors for cochlear implant (CI). To analyze whether postoperative speech perception performance could be predicted using DR change and initial NRT. SUBJECTS AND METHODS: The speech comprehension data of 33 patients with CI were retrospectively analyzed after 1, 3, 6, and 12 months of device use. All subjects were adult, postlingually hearing-impaired, and Cochlear Nucleus CI users. Speech perception performance was evaluated using aided pure tone audiometry, consonant, vowel, one-word, two-word, and sentence tests. RESULTS: The averages of initial NRT and DR changes were 197.8±25.9 CU (104-236) and 22.2±18.4 CU (-15-79), respectively. The initial DR was 40.8±16.6 CU. The postoperative DR was 50.3±16.4 CU at 3 months, 58±12.3 CU at 6 months, and 62.9±10.4 CU at 12 months. A gradual increase of DR was observed during the first year of CI. Compared with the initial DR, significant increases in DR were observed at 3 (p<0.05), 6 (p<0.001), and 12 (p<0.001) months. Compared with initial speech performance outcomes, a significant gain in all performance outcomes was achieved at 12 months (p<0.001). CONCLUSIONS: Patients with low NRT after CI surgery could initially set DR to a wider range and had better final speech perception outcomes. Conversely, patients with high NRT after CI surgery had to set up a gradual increase in DR while adjusting the T-C level, and the final speech perception outcomes were worse. DR and NRT, the main CI mapping variables, can help predict prognosis related to speech perception outcomes after CI surgery. In conclusion, the post-CI speech perception is better with a lower initial NRT, wider final DR, or younger age.

Improved Prediction of Hearing Loss after Temporal Bone Fracture by Applying a Detailed Classification for Otic Capsule-Violating Fracture: A Wide Scope Analysis with Large Case Series.

INTRODUCTION: This study aimed to analyze the predictability of temporal bone (TB) fracture-associated hearing loss by applying a detailed classification separating individual injury of the cochlea, vestibule, and semicircular canals (SCC). METHODS: In this retrospective study, patients with otic capsule-violating (OCV) fractures were further classified as OCV-C(VS) when the cochlea was involved regardless of vestibule or SCC involvement, OCV-V(S) when the vestibule was involved regardless of SCC involvement, and OCV-S when the fracture only involved SCC. Hearing changes were compared by applying the above-mentioned classification, and TB fracture-induced facial palsy was also analyzed. RESULTS: A total of 119 patients were included. Patients with OCV fractures had significantly worse bone conduction (BC) and air conduction (AC) thresholds (59.1 ± 25.3 and 87.0 ± 29.5 dB) than those with otic capsule-sparing (OCS) fractures (20.1 ± 17.9 and 36.5 ± 21.9 dB; p < 0.001 for each comparison). The BC and the AC thresholds of OCV-C(VS) (77.5 ± 11.0 and 114.2 ± 14.3 dB) and OCV-V(S) (69.3 ± 27.7 and 98.0 ± 22.2 dB) were significantly higher than OCV-S (40.1 ± 22.9 and 62.1 ± 25.6 dB; p < 0.001 for each comparison). The BC hearing thresholds were not significantly improved in the last pure tone audiometry when compared for total, OCV, or OCS cases. The AC threshold significantly improved in OCS cases. In a considerable number of cases with facial palsy, causative fracture lines involved the geniculate ganglion or tympanic segment without the involvement of the otic capsule. Most cases showed significant improvement; however, recovery was limited in cases with obvious fallopian canal disruption. CONCLUSIONS: The cases with sole involvement of SCC had significantly better hearing thresholds than those with cochlear or vestibule involvement, even in OCV fracture cases.

Protective Effect of Agmatine Against Cisplatin- Induced Cellular Apoptosis in an Auditory Cell Line.

BACKGROUND: The aims of this study were to evaluate the protective effects of agmatine against cisplatin-induced cellular apoptosis in an audi- tory cell line and to prove the protective mechanism of agmatine. METHODS: The House Ear Institute-Organ of Corti 1 cells were co-treated with agmatine at different concentrations and 15 µM of cisplatin for 48 hours. Cell viability and proliferation were measured. Annexin V-fluorescein isothiocyanate /propidium iodide staining was performed to analyze apoptosis. The levels of intracellular reactive oxygen species were measured using flow cytometry. The expression of BCL2-associated X protein and the enzymatic activity of caspase-3 was measured to examine the pathway of apoptosis induction. RESULTS: In normal conditions, the maximal protective effect occurred with 10 mM of agmatine. However, in the presence of cisplatin, the maximal protective effect was observed from 8 mM of agmatine. Thus, 8 mM was chosen as the ideal agmatine concentration for the analysis of protective effects against cisplatin-induced cytotoxicity. Agmatine exerted a significant protective effect against 15 µM of cisplatin when applied for 48 hours and reduced the proportion of necrotic and late apoptotic cells. Agmatine did not significantly reduce the cisplatin-induced increase in reactive oxygen species but decreased the expression of BCL2-associated X protein and the activity of caspase-3. CONCLUSION: Agmatine protected against cisplatin-induced cellular apoptosis in an auditory cell line. These effects were mediated by the pro- tection of mitochondrial function and inhibition of apoptosis.

Exploratory fall risk and preventive intervention in acute vestibular neuritis.

OBJECTIVE: To analyze recovery from dizziness in patients with acute vestibular neuritis (AVN) after applying the "Dizziness & Fall Risk Assessment and Intervention (DFRAI)". METHODS: This prospective study involved patients with AVN who underwent a survey of dizziness and fall risk. The patients received medical treatment and customized vestibular rehabilitation, and vestibular function was evaluated at the initial attack and 3 months later. RESULTS: Forty-one patients underwent subjective questionnaire assessments, which showed significant improvement in visual analog scale-dizziness handicap inventory-fear of falling (VAS-DHI-FOF) results from the initial vertigo attack to 3 months later. In the sensory organization test (SOT), the initial composite score was 63 ± 13.1, which improved to 77.5 ± 4.9 3 months later. In caloric testing, the canal paresis (CP) score was 42.9 ± 35.2, which improved to 29.9 ± 23.5 3 months later. CONCLUSIONS: Subjective improvement in dizziness and objective recovery of vestibular function were confirmed. DFRAI is a comprehensive solution for dizziness, and appropriate application of the DFRAI is expected to have a positive effect on recovery from dizziness and fall prevention in patients with AVN.

Evidence of Cochlear Synaptopathy and the Effect of Systemic Steroid in Acute Idiopathic Tinnitus With Normal Hearing.

OBJECTIVE: To evaluate the electrophysiologic evidence of cochlear synaptopathy and the effects of systemic steroids in acute idiopathic tinnitus with normal hearing. STUDY DESIGN: Retrospective review of medical data. SETTING: Tertiary referral center. PATIENTS: Fifty-nine patients who experienced acute-onset idiopathic tinnitus (within 12 weeks) with normal hearing and the same number of age- and pure-tone threshold-matched control groups. INTERVENTION: Electrophysiologic studies of the auditory pathway, oral steroids, and ginkgo biloba. MAIN OUTCOME MEASURES: Pure-tone thresholds, wave I and wave V amplitudes of the auditory brainstem response (ABR), tinnitus handicap inventory (THI), and visual analog scale (VAS). RESULTS: Significantly reduced ABR wave I amplitude and wave I/wave V ratio were found in the tinnitus group compared with the no tinnitus group. Age and pure-tone threshold were significantly correlated with reduced wave I amplitude and small wave I/wave V ratio. The THI and VAS scores were decreased at 3 and 12 weeks after steroid administration; however, overall changes in THI and VAS scores were not significantly different between the steroid and ginkgo biloba groups. CONCLUSION: Potential cochlear synaptopathy was suspected in the early stage of acute idiopathic tinnitus, even in patients with normal hearing. Age and hearing threshold were potentially associated with the development of cochlear synaptopathy. Low-dose oral steroids and ginkgo biloba induced early subjective relief of tinnitus, which maintained up to 12 weeks, however, those changes did not differ between groups.

Effects of Glycemic Control on Hearing Outcomes in Diabetes Patients With Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: This study aimed to analyze the effects of glycemic control on the hearing outcomes of type 2 diabetes patients with idiopathic sudden sensorineural hearing loss (ISSHL). METHODS: Type 2 diabetes patients with ISSHL were enrolled. All patients were admitted for 5 days and received systemic corticosteroid treatment. Patients were divided into groups according to their degree of glycemic control pre- (glycosylated hemoglobin) and post- (mean blood glucose) onset of ISSHL. Demographic, audiometric, and hearing outcome data were analyzed. Furthermore, a multivariate analysis was performed to determine the prognostic factors affecting the hearing outcomes in these patients. RESULTS: One hundred forty-four patients were enrolled. The hearing recovery rates were as follows: complete recovery, 19%; partial recovery, 15%; slight improvement, 22%; and no improvement, 44%. Initial hearing levels and diabetes duration were significantly higher in the pre-onset poor-controlled group (glycosylated hemoglobin ≥ 7.0%) than those in the well-controlled group. The hearing recovery rates did not differ significantly pre- or post-onset. In a multivariate analysis, duration from hearing loss onset to treatment, presence of vertigo, and initial hearing level were negative prognostic factors that affected hearing recovery. CONCLUSION: The degree of pre- or post-onset glycemic control did not affect hearing outcomes in patients with ISSHL and type 2 diabetes. Therefore, the administration of systemic corticosteroid is required for diabetes patients with ISSHL within allowable blood glucose levels.

Nationwide Analysis of Mortality Rates and Related Surgical Procedures in Hearing Disability Patients in South Korea.

BACKGROUND AND OBJECTIVES: Hearing loss (HL) and its repercussions are major problems in today's society. There are limited data on the relationship between degree of HL and otologic disorders. The aim of this study is to estimate mortality rates, rates of sudden idiopathic HL and related otologic surgical procedures in hearing disability patients in South Korea. SUBJECTS AND METHODS: Retrospective medical data for 160,205 patients with hearing disability was extracted. Mortality rates, rates of sudden idiopathic HL and related otologic surgical procedures were compared with a normal control group consisting of 865,475 people; approximately 5 times the number of hearing disability patients. RESULTS: According to the Korean National Disability Registry (NDR), 0.458% of the population in South Korea suffered from hearing disability in 2015. Higher rates of mortality and sudden idiopathic HL were reported in hearing disability patients, increasing up to a maximum of 1.594 times and 1,039.695 times, respectively, compared to the normal control group. Mastoidectomy surgery was 2.5 times more frequently performed and pressure equalizing (PE) tube insertion was about 15 times more frequently performed in hearing disability patients. CONCLUSIONS: Hearing disability is related to higher risks of mortality, sudden idiopathic HL and otologic surgical procedures, including mastoidectomy and PE tubing.

Psychiatric Distress as a Common Risk Factor for Tinnitus and Joint Pain: A National Population-Based Survey.

OBJECTIVES: This study aimed to investigate the relationship between tinnitus and joint pain from representative samples of Koreans. METHODS: The demographics and the responses to a questionnaire about tinnitus and joint pain severity and mental health status of adults aged ≥50 years in the 2010-2012 Korean National Health and Nutrition Examination Survey were analyzed. RESULTS: Among 9,032 individuals, 26.7% reported experiencing tinnitus within the past year. Participants with tinnitus were more frequently older, hearing loss, and had lower education levels, income, and body weight. Participants with regular exercise and sleep had a lower tinnitus prevalence. The incidences of stress, depressed mood, and suicidal ideation were significantly higher in the tinnitus group and participants with joint pain. The rates of participants with tinnitus according to the number of joint pain sites (zero, one, two, and three) was 22.1%, 31.4%, 33.3%, and 44.2%, and those of participants with severely annoying tinnitus according to the number of joint pain sites (zero, one, two, and three) were 3.3%, 6.8%, 7.9%, and 10.7%, respectively. CONCLUSION: Tinnitus prevalence and severity were significantly related to joint pain, and both conditions were related to psychiatric distress. Thus, the authors suggest that psychiatric distress as a common risk factor for tinnitus and joint pain should be considered when deciding treatment strategies and in guiding public health policy.

The optimal and safe intensity for facial nerve stimulation during intraoperative neuromonitoring in middle ear surgery.

OBJECTIVE: This study aimed to investigate the optimal and safe intensity for facial nerve stimulation during middle ear surgery. METHODS: Thirty-seven patients who had their facial nerve exposed prior to surgery were prospectively enrolled in this study, and electromyography (EMG) recordings were obtained from the orbicularis oculi and orbicularis oris muscles. Four pigs were also enrolled in an animal study, and continuous stimulation was performed on the facial nerves of the pigs for 10 minutes. The EMG responses were measured and the pathologic outcomes of the facial nerve after stimulation were determined. RESULTS: In the human study, the mean intensity of the minimal electrical stimulation threshold was 0.21 mA (range: 0.1-0.3 mA). A linear correlation was observed between stimulus intensity and response amplitude for intensities below 0.4 mA. Response amplitudes reached a plateau between 0.4 mA and 1.0 mA. The minimal stimulus intensity that could generate a maximal response was 0.4 mA in the orbicularis oculi (244 µV) and orbicularis oris (545 µV). In the animal study, there were no observed changes in EMG or nerve damage incidence after the continuous stimulation of 3.0 mA. CONCLUSIONS: 0.4 mA is considered to be the optimal intensity of facial nerve stimulation during middle ear surgery, and it was estimated through the animal study that a stimulation of 3.0 mA is safe from facial nerve damage.

Analysis of Inner Ear Anomalies in Unilateral Congenital Aural Atresia Combined With Microtia.

OBJECTIVES: The aim of this study was to analyze the incidence of inner ear anomalies in patients with unilateral congenital aural atresia (CAA) combined with microtia. METHODS: We retrospectively reviewed 61 patients with unilateral CAA combined with microtia who underwent high-resolution temporal bone computed tomography (TBCT) and hearing examination. Inner ear anomalies were analyzed using TBCT and evaluated according to the Jahrsdoerfer grading system, Marx classification, and extent of inferior displacement of the mastoid tegmen. RESULTS: Inner ear anomalies were observed in 14 patients (23.0%). Lateral semicircular canal (LSCC) dysplasia was the most common inner ear anomaly, with an incidence of 16.4%. The incidence was significantly higher on the pathologic side than on the unaffected side (P=0.002). All vascular anomalies were observed in the high-riding jugular bulb, with an incidence of 24.6%. The incidence was significantly higher on the pathologic side than on the unaffected side (P<0.001). LSCC dysplasia was significantly more common in patients with a lower Jahrsdoerfer score (odds ratio, 0.66; P=0.004). CONCLUSION: The incidence of inner ear anomalies was relatively high in patients with unilateral CAA combined with microtia; LSCC dysplasia was the most common anomaly and the probability of coexistence was higher in patients with a lower Jahrsdoerfer score.

One-Stage Complete Resection of Cholesteatoma With Labyrinthine Fistula: Hearing Changes and Clinical Outcomes.

OBJECTIVES: To evaluate long-term hearing changes and surgical outcomes for middle ear cholesteatoma with labyrinthine fistula following complete surgical removal of the cholesteatoma matrix. METHODS: Consecutive samples of 43 patients who underwent 1-stage complete resection of the cholesteatoma matrix overlying a labyrinthine fistula were obtained. Immediate and long-term hearing changes were analyzed in association with fistula size. Accuracy of various diagnostic examinations was assessed. RESULTS: Immediately postsurgery, the average bone conduction threshold (43.34 dB) did not differ significantly from the preoperative value (36.66 dB, P = .083). There were also minimal changes thereafter (45.63 dB) without recurrent case over an average follow-up time of 38.3 months (range, 17-69 months). More than 10 dB hearing loss was found in 7 patients with a case of intraoperative perilymph leakage (2.3%), although 5 of them had had preoperative air conduction threshold above 90 dB. Their fistulas were significantly larger than those of patients without hearing loss ( P = .027). CONCLUSION: Although caution is required for total removal of a large fistula, owing to increased risk of postoperative hearing deterioration, 1-stage complete resection of cholesteatoma matrix on labyrinthine fistula could be effective in disease control and long-term hearing preservation.

Impact of Nicotine Exposure on Hair Cell Toxicity and Embryotoxicity During Zebrafish Development.

OBJECTIVES: Nicotine has various adverse effects including negative impacts associated with maternal exposure. In the current study, we examined nicotine-induced damage of hair cells and embryotoxicity during zebrafish development. METHODS: Zebrafish embryos were exposed to nicotine at several concentrations (5, 10, 20, and 40 µM) and embryotoxicity were evaluated at 72 hours, including hatching rate, mortality, teratogenicity rate, and heart rate. Hair cells within the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) neuromasts were identified at 120 hours. Apoptosis and mitochondrial damage of hair cells were analyzed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) and DASPEI (2-[4-(dimethylamino)styryl]-N-ethylpyridinium iodide) assays, respectively, and changes of ultrastructure were observed by scanning electron microscopy. RESULTS: The control group without nicotine appeared normal with overall mortality and teratogenicity rate <5%. The hatching rate and mortality rate was not significantly different according to nicotine concentration (n=400 each). The abnormal morphology rate (n=400) increased and heart rate (n=150) decreased with increasing nicotine concentration (P<0.05). Nicotine-induced hair cell damage significantly increased as nicotine concentration increased. A significantly greater number of TUNEL-positive cells (P<0.01) and markedly smaller DASPEI area (P<0.01) were shown as nicotine concentration increased. CONCLUSION: The current results suggest that nicotine induces dose-dependent hair cell toxicity in embryos by promoting apoptosis and mitochondrial and structural damage.

Analysis of Eustachian Tube Dysfunction by Dynamic Slow Motion Video Endoscopy and Eustachian Tube Dysfunction Questionnaire in Chronic Otitis Media.

OBJECTIVES: Eustachian tube dysfunction has been associated with most cases of middle-ear disease. We aimed to assess the effectiveness of dynamic slow motion video endoscopy (DSVE) as a test of eustachian tube dysfunction. Furthermore, we assessed the correlation of the test with the Valsalva maneuver, the seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7), and intraoperative findings of the eustachian tube. METHODS: We retrospectively reviewed medical records from April to September 2014 to identify patients who were diagnosed with chronic otitis media (COM) at Korea University Ansan Hospital. They all underwent surgery because of COM without cholesteatoma and were assessed via the DSVE and ETDQ-7 to determine eustachian tube function. RESULTS: We reviewed 46 COM patients and examined 46 ears with COM and 46 ears on the contralateral side to COM that were thought to be normal. The mean DSVE grade in COM ears was 1.57±0.96, while the mean DSVE grade in contralateral ears was 1.15±0.94. The difference in DSVE between COM ears and normal ears was statistically significant (P=0.006). In the ETDQ-7, a higher score was related to intraoperative obstruction of the eustachian tube (P=0.012). CONCLUSION: DSVE and ETDQ-7 can provide information regarding preoperative status of eustachian tube dysfunction by measuring dynamic structural changes of the eustachian tube in combination with other diagnostic tests.

Comparison of the effects of lipoic acid and glutathione against cisplatin-induced ototoxicity in auditory cells.

OBJECTIVES: The aims of this study were to examine lipoic acid (LA)- or glutathione (GSH)-mediated protection against cytotoxicity following cisplatin exposure in HEI-OC1 auditory cells and measure the potential of LA and GSH to scavenge reactive oxygen species (ROS). This study also compares their protective effects and discusses the determination of a preventive or therapeutic dose. METHODS: HEI-OC1 cells were pretreated with LA or GSH for 24 h and then exposed to 15 µM cisplatin for 48 h. The resulting cytotoxicity was measured using a cell counting kit-8, and intracellular ROS level was measured using flow cytometry. The protective or anti-ROS effects of LA and GSH were compared. Measurement of caspase 3, 8, 9 activity and Western blot analysis of PARP were performed. RESULTS: Pretreatment with LA at 300 µM and GSH at 3 mM protected HEI-OC1 cells against cisplatin-induced cytotoxicity and significantly reduced the cisplatin-induced increase in ROS. LA showed a significantly more effective protection against cisplatin-induced ototoxicity compared to that shown by GSH (85.4% vs. 73.1% cell viability). Both LA and GSH showed the maximal protective effect at different concentrations in normal or cisplatin-induced cytotoxic conditions. The preventive or therapeutic dose for harmful conditions is quite different for the two drugs and needs careful adjustments. CONCLUSION: This comparative study on the protective effects of LA and GSH against cisplatin-induced ototoxicity in an auditory cell line posed many challenges. Although LA and GSH showed a significant protective effect against cisplatin, the LA's effect was superior. The concentration at which the maximal protective effect of LA or GSH was noted was 3 times higher in cytotoxic conditions than in normal conditions, which suggests the need for drug dose adjustments based on the purpose (preventive or therapeutic).

Effect of Tianeptine on Depressed Tinnitus Patients.

BACKGROUND AND OBJECTIVES: Tianeptine is a tricyclic antidepressant that has a novel pharmacological property: it increases the reuptake of 5-hydroxytryptamine. Recent studies have reported that the prevalence of depression is greater in patients with tinnitus than in control subjects who do not have tinnitus. The purpose of this study was to assess the efficacy of tianeptine for the relief of tinnitus, especially in patients with depressive mood. SUBJECTS AND METHODS: Among a total of 52 tinnitus patients, 15 had depressive mood. The depressed tinnitus patients were prescribed Stablon® 12.5 mg once daily for 1 month without any other drug. We assessed the severity of tinnitus, level of depression, and the quality of sleep in these patients by using the Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI). Hearing impairment and severity of tinnitus were measured with pure tone audiometry, speech audiometry, and tinnitograms. These evaluations were conducted before and after medication treatment. RESULTS: For the 15 depressed tinnitus patients, THI scores significantly correlated with BDI and PSQI scores prior to medication treatment. These results showed that the discomfort of tinnitus was closely related to depression and sleep disorder. After medication treatment, THI and BDI scores significantly decreased, indicating that tinnitus and depression improved. However, no significant alteration in PSQI score was observed, indicating that there was no improvement in sleep quality. CONCLUSIONS: In the treatment of depressed tinnitus patients, tianeptine might be an efficient drug to treat both tinnitus and depression. However, tianeptine is unlikely to improve the quality of sleep in these patients.

The suppressive effects of metformin on inflammatory response of otitis media model in human middle ear epithelial cells.

OBJECTIVE: Metformin is a well-known anti-diabetic agent, but its mechanism is unclear. Recently, many reports have described the anti-inflammatory effects of metformin on various cell types, including human vascular smooth muscle cells and endothelial cells. This study was designed to investigate the anti-inflammatory effect of metformin on lipopolysaccharide (LPS) induced inflammation in human middle ear epithelial cell lines (HMEECs). METHODS: The effect of pretreatment by metformin (0, 1, 2, 4 mM) was evaluated by the inflammatory response in the HMEECs exposed to LPS (10 ng/ml). For verifying the suppression effect of metformin on the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) was evaluated by real-time polymerase chain reaction, and COX-2 protein was assessed by western blotting. Intracellular reactive oxygen species (ROS) was measured using 2', 7'-dichlorofluorescein diacetate (DCFHDA) fluorocytometer. RESULTS: Stimulation by LPS 10 ng/ml concentration showed 12.4 folds increase the expression of TNF-α mRNA compared to control on HMEECs. Pretreatment of metformin dose dependently suppressed the expression of TNF-α mRNA induced by LPS (2 mM, p = 0.03). The amount of COX-2 protein production was significantly decreased by metformin pretreatment (4 mM, p = 0.01). The production of ROS was decreased significantly by pretreatment of metformin (p = 0.03). CONCLUSIONS: These findings suggest that the inflammatory response and oxidative stress induced by LPS could be suppressed by metformin in HMEECs. Therefore, metformin may have a therapeutic potential for the treatment of the otitis media.

The effects of the antioxidant α-tocopherol succinate on cisplatin-induced ototoxicity in HEI-OC1 auditory cells.

CONCLUSION: D-α-tocopherol succinate significantly reduced a cisplatin-induced hair cell loss in HEI-OC1 cell lines. These effects were mediated by its scavenging activity against reactive oxygen species (ROS) and inhibition of apoptosis. OBJECTIVES: Alpha-tocopherol is a class of methylated phenols, known as fat-soluble antioxidants, and is a different form of vitamin E, which reduces free radicals and acts as an antioxidant. We hypothesized that the antioxidative effect of α-tocopherol could protect against cisplastin-induced cytotoxicity, and thus evaluated its effects on cisplatin-induced ototoxicity in HEI-OC1 auditory cells. METHODS: HEI-OC1 cells were pretreated with D-α-tocopherol succinate at a concentration of 10 µM for 24 h, and then exposed to 15 µM cisplatin for 48 h. The cellular viability was measured by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The intracellular ROS level was measured by using a fluorescent dye, 2',7'-dichlorofluorescein diacetate (DCFH-DA). Both Annexin V-FITC and propidium iodide (PI) staining were performed to analyze the pattern of apoptosis. The enzymatic activity of caspase-3 was assayed with caspase3/CPP32 fluorometric assay kit. Also, it was assessed by immunoblotting technique of poly-ADP-ribose polymerase (PARP). RESULTS: Pretreatment with 10 µM D-α-tocopherol succinate protected HEI-OC1 auditory cells against cisplatin-induced cytotoxicity. D-α-tocopherol succinate significantly reduced the cisplatin-induced increase in ROS. D-α-tocopherol succinate treatment induced a 15% reduction of ROS and 50% decrease in necrosis and late apoptosis as compared to cisplatin treatment. D-α-tocopherol succinate also decreased the activation of caspase-3 and reduced levels of cleaved poly-ADP-ribose polymerase (PARP).

Analysis of audio-vestibular assessment in acute low-tone hearing loss.

Conclusion This study demonstrated excellent hearing recovery following the combined treatment of diuretic and oral steroid, and electrocochleography (ECoG) was significantly higher than normal side. This study reports characteristics of acute low-tone hearing loss (ALHL) that show the greater low-tone hearing loss, the higher ECoG, and excellent recovery, even-though low-tone hearing loss is worse, which can be different compared with sudden deafness. Objective To analyze ALHL without vertigo, this study compared the ALHL group with all patients exhibiting low-tone hearing loss and ear fullness. Hearing changes and vestibular functions were analyzed. Materials and methods ALHL was defined as a mean hearing loss of ≥ 30 dB at 125, 250, and 500 Hz, and ≤ 20 dB at 2, 4, and 8 kHz. From 156 cases of low-tone hearing loss of more than 10 dB without vertigo, 31 met the ALHL criteria and were subjected to audio-vestibular assessments including PTA, ECoG, vestibular evoked myogenic potential (VEMP) testing, and caloric testing. Results In ALHL, low-tone hearing loss was 42.7 ± 9.5 dB, and 83.9% of ALHL significantly recovered by more than 10 dB. The ECoG in ALHL was 0.334 ± 0.11 (higher than 0.25 ± 0.08 on the normal side) and ECoG abnormality was 35.5% (the greater low-tone hearing loss, the higher ECoG value).

Sodium Selenite Acts as an Otoprotectant against Neomycin-Induced Hair Cell Damage in a Zebrafish Model.

Sodium selenite is a trace element essential for many physiological functions in the body. It is involved in various biological processes; it acts as a cofactor for antioxidant enzymes that protect against free radicals and is reported to limit metal-mediated oxidative DNA damage. In the present study, we investigated the effect of sodium selenite on neomycin ototoxicity in wild-type and transgenic zebrafish (Brn3C: EGFP). Five or six days post-fertilization, zebrafish larvae were co-exposed to 125 µM neomycin and various concentrations (10 µM, 100 µM, 250 µM, and 500 µM) of sodium selenite for 1 h. Hair cells within neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed by fluorescence microscopy (n = 10 fish per treatment). Hair cell survival was estimated as the ratio of the hair cell numbers in each group compared to those of the control group that were not exposed to neomycin. Apoptosis and hair cell damage of neuromasts were evaluated using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay and 2-[4-(dimethylamino) styryl]-N-ethylpyridinium iodide (DASPEI) assay, respectively. Ultrastructural changes were evaluated using scanning electron microscopy and transmission electron microscopy. Neuromast hair cells were preserved in zebrafish exposed to 125 µM neomycin and 500 µM sodium selenite for 1 h. Sodium selenite protected against neomycin-induced hair cell loss of neuromasts, reduced apoptosis, and prevented zebrafish ultrastructural changes. We propose that sodium selenite protects against neomycin-induced hair cell damage by inhibiting apoptosis, decreasing the disarray of stereocilia, and preventing ultrastructural changes in the neuromast hair cells of the zebrafish.