Increased Hearing Thresholds Research Articles

Effect of Cigarette Smoking and Passive Smoking on Hearing Impairment: Data from a Population-Based Study.

ObjectivesIn the present study, we aimed to determine the effect of both active and passive smoking on the prevalence of the hearing impairment and the hearing thresholds in different age groups through the analysis of data collected from the Korea National Health and Nutrition Examination Survey (KNHANES).Study DesignCross-sectional epidemiological study.MethodsThe KNHANES is an ongoing population study that started in 1998. We included a total of 12,935 participants aged ≥19 years in the KNHANES, from 2010 to 2012, in the present study. Pure-tone audiometric (PTA) testing was conducted and the frequencies tested were 0.5, 1, 2, 3, 4, and 6 kHz. Smoking status was categorized into three groups; current smoking group, passive smoking group and non-smoking group.ResultsIn the current smoking group, the prevalence of speech-frequency bilateral hearing impairment was increased in ages of 40−69, and the rate of high frequency bilateral hearing impairment was elevated in ages of 30−79. When we investigated the impact of smoking on hearing thresholds, we found that the current smoking group had significantly increased hearing thresholds compared to the passive smoking group and non-smoking groups, across all ages in both speech-relevant and high frequencies. The passive smoking group did not have an elevated prevalence of either speech-frequency bilateral hearing impairment or high frequency bilateral hearing impairment, except in ages of 40s. However, the passive smoking group had higher hearing thresholds than the non-smoking group in the 30s and 40s age groups.ConclusionCurrent smoking was associated with hearing impairment in both speech-relevant frequency and high frequency across all ages. However, except in the ages of 40s, passive smoking was not related to hearing impairment in either speech-relevant or high frequencies.

Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome.

The patients with DiGeorge syndrome (DGS), caused by deletion containing dozens of genes in chromosome 22, often carry cardiovascular problem and hearing loss associated with chronic otitis media. Inside the deletion region, a transcription factor TBX1 was highly suspected. Furthermore, similar DGS phenotypes were found in the Tbx1 heterozygous knockout mice. Using ENU-induced mutagenesis and G1 dominant screening strategy, here we identified a nonsynonymous mutation p.W118R in T-box of TBX1, the DNA binding domain for transcription activity. The mutant mice showed deficiency of inner ear functions, including head tossing and circling, plus increased hearing threshold determined by audiometry. Therefore, our result further confirms the pathogenic basis of Tbx1 in DGS, points out the crucial role of DNA binding activity of TBX1 for the ear function, and provides additional animal model for studying the DGS disease mechanisms.

Hearing Aid Use and Associated Factors in South Korea.

Despite the high prevalence of hearing impairment in the elderly, the rate of hearing aid use is still low. The objectives of this study were to report the nation-wide prevalence of hearing aid use in the Korean population and to determine the associated factors with hearing aid use utilizing a nationally representative data set.We obtained data from the 2010 to 2012 Korea National Health and Nutrition Examination Surveys, which were cross-sectional surveys of the civilian, noninstitutionalized population of the Republic of Korea at age ≥40 years (N = 12,709). A field survey team performed interviews as well as physical examinations. Hearing aid use was assessed using an interviewer-administered questionnaire and pure-tone audiometry was administered for all participants in a sound-attenuating booth. Prevalence of hearing aid acquisition and regular use were calculated in participants who reported perceived hearing loss and who have bilateral hearing thresholds exceeding the 40 dB hearing level. Multivariable analyses were used to examine the associated factors with hearing aid use.The prevalence of hearing aid acquisition and regular use was 17.4% and 12.6%, respectively, in South Korea. Increased hearing threshold (OR 1.05, 95% CI 1.03–1.07), severe perceived hearing loss (OR 10.73, 95% CI 4.52–25.46), annoying tinnitus (OR 3.30, 95% CI 1.61–6.74), balance problems (OR 0.39, 95% CI 0.18–0.86), and myopia (OR 0.30, 95% CI 0.12–0.76) were associated factors of regular use of hearing aids.The prevalence of hearing aid use in Korea is relatively low. Finding relevant factors of hearing aid use could provide further insight in setting up hearing-rehabilitation strategy for the elderly with significant hearing loss.

Association of hearing impairment with chronic kidney disease: a cross-sectional study of the Korean general population.

BackgroundWe aimed to evaluate the association between hearing impairment and the prevalence of chronic kidney disease (CKD) in the largest population-based cross-sectional study to date.MethodsThis cross-sectional study was based on the Korean National Health and Nutritional Examination Survey (KNHANES). It included 5226 participants ≥19 years of age whose estimated glomerular filtration rate (eGFR) and hearing threshold had been measured. We diagnosed CKD as an eGFR <60 mL/min/1.73 m2. The participants were also evaluated for the presence of other contributing factors related to kidney dysfunction. We divided the participants at the 40-dB threshold into hearing-impairment and no-hearing-impairment groups, using the average threshold of all six frequencies (500, 1000, 2000, 3000, 4000, and 6000 Hz) for both ears.ResultsThe odds of hearing impairment was 1.25 times higher (95 % confidence interval: 1.12–1.64, p-value < 0.001) in participants with an eGFR <60 mL/min/1.73 m2 than in those with an eGFR ≥60 mL/min/1.73 m2 after adjustments for age, sex, smoking, alcohol, body mass index, diabetes mellitus, hypertension, dyslipidemia, and microalbuminuria. Among the risk parameters of CKD associated with hearing impairment, linear regression analysis adjusted for age and sex determined that each increase of serum creatinine or blood pressure was positively associated with an increase in hearing threshold (p-value < 0.01).ConclusionThe odds of hearing impairment were greater with lower eGFR than with normal eGFR. Individuals with CKD were more likely to also have hearing impairment. We recommend screening the hearing of patients with CKD to provide earlier identification of hearing impairment and earlier intervention, thereby preventing progression of hearing impairment and providing appropriate treatment strategies.

Macrophage Migration Inhibitory Factor Deficiency Causes Prolonged Hearing Loss After Acoustic Overstimulation.

Macrophage migration inhibitory factor plays an important role in noise-induced hearing loss. Macrophage migration inhibitory factor is an essential factor in axis formation and neural development. Macrophage migration inhibitory factor is expressed in the inner ear, but its function remains to be elucidated. Macrophage migration inhibitory factor-deficient mice (MIF(-/-) mice) were used in this study. Wild-type and MIF(-/-) mice received noise exposure composed of octave band noise. Auditory brainstem response thresholds were examined before (control) and at 0, 12, and 24 hours and 2 weeks after the intense noise exposure. Morphological findings of cochlear hair cells were investigated using scanning electron microscopy. Histopathological examination with hematoxylin and eosin staining and TUNEL assay were also performed. In both the wild-type and MIF(-/-) mice, acoustic overstimulation induced significant hearing loss compared with the control level. Two weeks after the intense noise exposure, the MIF(-/-) mice had an increased hearing threshold compared with the wild-type mice. Scanning electron microscopy demonstrated that the outer hair cells in the MIF(-/-) mice were affected 2 weeks after noise exposure compared with the wild-type mice. TUNEL-positive cells were identified in the organ of Corti of the MIF(-/-) mice. The MIF(-/-) mice had prolonged hearing loss and significant loss of cochlear hair cells after intense noise exposure. Macrophage migration inhibitory factor may play an important role in recovery from acoustic trauma. Management of macrophage migration inhibitory factor may be a novel therapeutic option for noise-induced hearing loss.

The association between metabolic syndrome or chronic kidney disease and hearing thresholds in Koreans: the Korean National Health and Nutrition Examination Survey 2009-2012.

BackgroundThe aim of this study was to determine whether metabolic syndrome (MetS) or chronic kidney disease (CKD) is associated with hearing thresholds in the general Korean population.Patients and MethodsA total of 16,554 participants were included in this study. MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III guidelines, and CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or a dipstick proteinuria result of ≥1+. The hearing thresholds were measured at 0.5, 1, 2, 3, 4, and 6 kHz. Low-frequency (Freq) was defined as pure-tone averages at 0.5 and 1 kHz, while Mid-Freq and High-Freq were defined as the average thresholds at mid-frequency (2 and 3 kHz) and high frequency (4 and 6 kHz), respectively.ResultsIn men, the hearing thresholds were 15.1 ± 14.5 dB, 22.2 ± 21.3 dB, and 37.3 ± 26.5 dB for Low-, Mid-, and High-Freq, respectively. In women, the hearing thresholds were 14.9 ± 15.3 dB, 16.6 ± 18.0 dB, and 26.1 ± 21.5 dB for Low-, Mid-, and High-Freq, respectively. The hearing thresholds for men were significantly higher than the hearing thresholds for women in all 3 threshold categories. Male and female subjects with MetS or CKD had higher hearing thresholds than the subjects that did not have these disorders. In the multivariate analysis, MetS was associated with increased hearing thresholds in women, and CKD was associated with increased hearing thresholds in men and women.ConclusionMetS is associated with hearing thresholds in women, and CKD is associated with hearing thresholds in men and women. Therefore, patients with MetS or CKD should be closely monitored for hearing impairment.

Hearing loss in geriatric hemodialysis patients

Introduction: The aim of the study was to evaluate the hearing loss in geriatric hemodialysis patients. Materials and Methods: The study was performed on 16 geriatric hemodialysis patients (age minimum: 65, maximum: 86 years) and 16 volunteers (age minimum: 65, maximum: 86 years) as a control group. The patients' pure tone audiometry values between 250 and 8000 Hz frequencies were analyzed. Results: In our study, statistical significance was found between hearing loss and serum urea levels (P = 0.001). Hearing loss values were not statistically significantly different between the study and control groups (P = 0.786). High frequency hearing thresholds were found to be significantly higher in the geriatric hemodialysis patients (P = 0.032). Normal hearing levels at all levels were found in 5 patients in the study group. Mild to moderate hearing loss was found in 11 patients. Conclusions: In our preliminary study, we found statistically significant differences between the increase in hearing thresholds and uremia. Statistically significant changes in hearing thresholds at high frequencies were found between the two groups. Long-term hemodialysis treatment of 10 years or more is a risk factor for hearing loss. Hemodialysis treatment is a risk factor for hearing loss in geriatric patients who are at a risk of presbyacusis.

Gestational exposure to polychlorinated biphenyls and dibenzofurans induced asymmetric hearing loss: Yucheng children study

IntroductionIn 1979, approximately 2000 people in central Taiwan were exposed to polychlorinated biphenyls and dibenzofurans (PCBs/PCDFs) due to ingestion of contaminated rice oil. The children born to mothers exposed to PCBs/PCDFs were called Yucheng children. We conducted a follow-up study to examine the association between gestational PCBs/PCDFS exposure and auditory function in Yucheng children's early adulthood. MethodsIn 1985 and early 1992, Yucheng children and their age, gender, socio-economic matched unexposed referent children were recruited for physical examination and long-term follow-ups. In 2007, Yucheng children and referent children were invited to participate in a health examination, including assessment of pure-tone air-conduction thresholds and distortion product otoacoustic emissions (DPOAEs) test. Gestational exposure to PCBs/PCDFs in Yucheng children were estimated by back-extrapolation of their mother's serum concentration to the time of childbirth. ResultsA total of 86 Yucheng children (51.2% males) and 97 referent children (50.5% males) were included for analysis. No difference was found in demographic characteristics between two groups. Among the Yucheng children, 53 had estimated PCBs/PCDFs concentrations. We found that Yucheng children were at higher risk of having elevated hearing threshold at low frequencies in the right ear. Estimated maternal concentrations of 2,3,4,7,8-pnCDF at the time of birth were associated with increased hearing thresholds and decreased DPOAEs amplitudes at low frequencies in the right ear. ConclusionGestational exposure to PCBs/PCDFs caused adverse asymmetrical hearing effects detectable even in early adulthood.

Gap detection and temporal modulation transfer function as behavioral estimates of auditory temporal acuity using band-limited stimuli in young and older adults.

Gap detection and the temporal modulation transfer function (TMTF) are 2 common methods to obtain behavioral estimates of auditory temporal acuity. However, the agreement between the 2 measures is not clear. This study compares results from these 2 methods and their dependencies on listener age and hearing status. Gap detection thresholds and the parameters that describe the TMTF (sensitivity and cutoff frequency) were estimated for young and older listeners who were naive to the experimental tasks. Stimuli were 800-Hz-wide noises with upper frequency limits of 2400 Hz, presented at 85 dB SPL. A 2-track procedure (Shen & Richards, 2013) was used for the efficient estimation of the TMTF. No significant correlation was found between gap detection threshold and the sensitivity or the cutoff frequency of the TMTF. No significant effect of age and hearing loss on either the gap detection threshold or the TMTF cutoff frequency was found, while the TMTF sensitivity improved with increasing hearing threshold and worsened with increasing age. Estimates of temporal acuity using gap detection and TMTF paradigms do not seem to provide a consistent description of the effects of listener age and hearing status on temporal envelope processing.

Statistical Analysis of Various Factors Affecting the Results of Cochlear Implantation

analysis of several factors was performed to reveal any significant effect of the outcome of the procedure. RESULTS: The duration of deafness in adults showed a significant linear yet non-monotonic correlation with the postoperative average auditory thresholds as revealed by Pearson’s correlation coefficient (r=0.839, p=0.009) and a linear regression model (f=14.211, p=0.009), which showed that the increase in the duration of deafness led to an increase in hearing thresholds and accounted for 70.3% of the variance in the outcome (β=0.839, t=3.770, and p=0.009). Age at implantation in children showed a positive linear, monotonic relation with the postoperative receptive (r=0.725, p<0.001, r S =0.354, p=0.010) and was a significant predictor of outcome (β=0.440, t=2.961; p=0.005) according to multiple linear regression. Mann-Whitney U-test was performed to evaluate the difference in medians of outcomes in relation to the regularity of attendance to speech rehabilitation. We found a significant effect over the auditory hearing thresholds (the mean ranks of regulars and irregulars were 21.48 and 31.92, respectively; u=202.00, z=2.48, p<0.05) CONCLUSION: An increase in the duration of deafness leads to less favorable results of postoperative auditory thresholds in postlingual adults. Additionally, an increase in age at implantation may be associated with increased expressive language age in the first year postimplantation, and regular attendance to a speech rehabilitation program is associated with better postoperative auditory thresholds and a higher receptive language age.

Cochlear's unique electrode portfolio now and in the future

ObjectivesTo review Cochlear's electrode portfolio and discuss the merits of current and future straight and perimodiolar electrode arrays. To present an update on implant reliability.MethodsPerformance and hearing preservation data from studies involving the Slim Straight (CI422), Hybrid L24 and Contour Advance electrode array were reviewed.ResultsWhile several studies in past found little difference in performance outcomes between subjects implanted with perimodiolar and straight arrays, recent studies demonstrated that proximity to the modiolus is correlated with better performance. Hearing threshold increase was lowest with the Hybrid L24, closely followed by the slim straight array and was largest with the Contour Advance array. The CI24RE receiver-stimulator used for the three arrays had a cumulative survival of 99% at eight years post implantation.ConclusionsCombining the hearing preservation benefits of slim straight arrays with perimodiolar proximity is the design objective of Cochlear's next generation electrodes.

Vitamin C Deficiency–Induced Hearing Loss and Ossicular Defect in Transgenic Mice

Objectives: Certain forms of hearing loss (HL) are life-long disabilities that critically affect the development of language and cognition. Recent studies show that vitamin C (ascorbic acid; AA) can protect from hearing loss; while vitamin C deficiency (VCD) accelerates long bone loss. Humans are particularly sensitive to VCD due to genetically evolved disability to synthesize AA and require dietary supplementation. However, the effect of VCD on the ossicles and the underlying mechanisms have not been understood. In this study we used a transgenic VCD mouse model (sfx mice) to determine whether VCD can affect the maturation of the ossicles. Methods: Auditory function in sfx (GULO-/-) and control (GULO+/-) mice was measured with auditory brainstem responses (ABR) and distortion product otoacoustic emission (DPOAE). The middle ears were dissected and the morphological characteristics of the ossicles in sfx and control mice were evaluated with a stereoscopic microscopy. Results: The sfx mice developed spontaneous fracture and delayed growth at 6 weeks of age. The sfx mice showed significantly increased hearing thresholds in ABR ( P &lt; 0.05) and decreased DPOAE ( P &lt; 0.05). The bony structures of the external ear canal, middle ear walls and otic capsule of sfx mice were smaller and more friable as compared to control mice. All the ossicles in sfx mice were thinner than that of control mice. Conclusions: These findings suggest that VCD can induce ossicular defect and hearing loss in sfx mice. Further studies will illustrate the underlying mechanisms of ossicular defect related to osteoblast differentiation.

English

OBJECTIVE: Objective of the present study is to know the effect of cell phone usage on hearing thresholds. MATERIAL AND METHODS: Seventy students from 20-30 years of age were divided into two groups. Those using cell phone for more than one hour a day for past 5 years form the test group and those using for less than one hour for less than 5 years form the control group. Pure tone audiometry was done on all the subjects. RESULTS: There was a significant increase in hearing thresholds at all frequencies for both air conduction and bone conduction in both right ear and left ear, except for bone conduction at 4KHz. CONCLUSION: There was a significant increase in hearing thresholds in mobile phone users associated with duration of usage.

Neurophysiologic, audiometric and vestibular function tests in patients with hyperostosis cranialis interna

ObjectiveHyperostosis cranialis interna (HCI) is an autosomal dominant sclerosing bone dysplasia affecting the skull base and the calvaria, characterized by cranial nerve deficits due to stenosis of neuroforamina. The aim of this study is to describe the value of several neurophysiological, audiometric and vestibular tests related to the clinical course of the disorder. MethodsTen affected subjects and 13 unaffected family members were recruited and tested with visual evoked potentials, masseter reflex, blink reflex, pure tone and speech audiometry, stapedial reflexes, otoacoustic emissions, brainstem evoked response audiometry and electronystagmography. ResultsDue to the symmetrical bilateral nature of this disease, the sensitivity of visual evoked potentials (VEPs), masseter reflex and blink reflex is decreased (25–37.5%), therefore reducing the value of single registration. Increased hearing thresholds and increased BERA latency times were found in 60–70%. The inter-peak latency I–V parameter in BERA has the ability to determine nerve encroachment reliably. 50% of the patients had vestibular abnormalities. No patient had disease-related absence of otoacoustic emissions, because the cochlea is not affected. ConclusionIn patients with HCI and similar craniofacial sclerosing bone dysplasias we advise monitoring of vestibulocochlear nerve function with tone and speech audiometry, BERA and vestibular tests. VEPs are important to monitor optic nerve function in combination with radiological and ophthalmologic examination. We do not advise the routine use of blink and masseter reflex.

Abstract 355: Generation of a murine model of Neurofibromatosis Type 2 that accurately recapitulates the spontaneous development of vestibular and spinal schwannomas found in NF2 patients.

Abstract Neurofibromatosis type 2 (NF2) is a genetic disease resulting from germline loss of the NF2 tumor suppressor gene. The hallmark of NF2 is hearing and vestibular loss of function in young adults caused by the development of vestibular schwannomas, which occur bilaterally in nearly all patients and are associated with homozygous loss of NF2. Individuals affected with NF2 also acquire schwannomas of other cranial, spinal and peripheral nerves. Importantly, non-familial schwannomas, the most common tumor of the peripheral nervous system, are also caused by bi-allelic loss of NF2 gene function. A major limitation in the identification of genetic and pharmacologic targets for schwannomas has been the lack of a robust preclinical model that accurately recapitulates human NF2 disease. In order to develop a more robust model, we intercrossed a mouse expressing Cre Recombinase under the control of the 3.9PeriCre promoter with an Nf2 conditional knockout mouse previously generated by Dr. Marco Giovannini to conditionally ablate Nf2 in neural crest-derived cell populations. Histological analysis of the dorsal root ganglion (DRG) and proximal spinal nerves of 3.9PeriCre+;Nf2flox/flox mice revealed that intercrossed mice spontaneously develop tumors between 8 and 10 months at every single spinal level. Microscopic analysis implicated these tumors as schwannomas, as they display a dense pattern of cellularity consistent with the established criteria of GEM schwannoma, including S100β1 positivity. Quantitation of the DRG volume indicated that 3.9PeriCre+ mice have a statistically significant increase when compared to 3.9PeriCre- littermates. FDG-PET studies corroborated this finding, as comparative studies showed an increase in the metabolic activity of paraspinal tumors found in 3.9PeriCre+ mice. Auditory Brainstem Response testing has revealed that 3.9PeriCre+ mice acquire an age-dependent increase in hearing threshold by 8 months when compared to age-matched 3.9PeriCre- controls. Histological analysis of Cranial Nerve VIII confirmed that the hearing loss was directly associated with the development of vestibular schwannomas. To test for concomitant vestibular loss of function, three different behavioral studies (contact righting, trunk curl, and swim) were performed to isolate and test the integrity of the vestibular sense in 3.9PeriCre;Nf2flox/flox mice. These studies indicated that 3.9PeriCre+ mice develop vestibular deficits, as all three studies identified highly significant differences between the two genotypes. Collectively, these genetically engineered mice acquire a physiologic phenotype that closely recapitulates important features of human NF2 disease and provides opportunities for testing putative therapeutic targets using genetic intercrosses or novel small molecule inhibitors. Citation Format: Jeff R. Gehlhausen, Su Jung Park, Matthew Shew, Wade Clapp, Charles Yates. Generation of a murine model of Neurofibromatosis Type 2 that accurately recapitulates the spontaneous development of vestibular and spinal schwannomas found in NF2 patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 355. doi:10.1158/1538-7445.AM2013-355

Insensitivity of the audiogram to carboplatin induced inner hair cell loss in chinchillas

Noise trauma, aging, and ototoxicity preferentially damage the outer hair cells of the inner ear, leading to increased hearing thresholds and poorer frequency resolution.Whereas outer hair cells make synaptic connections with less than 10% of afferent auditory nerve fibers (type-II), inner hair cells make connections with over 90% of afferents (type-I). Despite these extensive connections, little is known about how selective inner hair cell loss impacts hearing. In chinchillas, moderate to high doses of the anticancer compound carboplatin produce selective inner hair cell and type-I afferent loss with little to no effect on outer hair cells. To determine the effects of carboplatin-induced inner hair cell loss on the most widely used clinical measure of hearing, the audiogram, pure-tone thresholds were determined behaviorally before and after 75 mg/kg carboplatin. Following carboplatin treatment, small effects on audiometric thresholds were observed even with extensive inner hair cell losses that exceed 80%. These results suggest that conventional audiometry is insensitive to inner hair cell loss and that only small populations of inner hair cells appear to be necessary for detecting tonal stimuli in a quiet background.

Hearing loss with phosphodiesterase‐5 inhibitors

To assess the effect of tadalafil on auditory functions. Prospective observational study in a tertiary care hospital. Twenty-five tadalafil naïve patients with erectile dysfunction or pulmonary artery hypertension were subjected to pure-tone and brainstem-evoked response audiometry before drug therapy, and 3 and 30 days following drug therapy. Results were compared using analysis of variance for repeated measures with Bonferonni correction. Fifteen patients were taking tadalafil 10 mg for erectile dysfunction, and another 10 patients were on tadalafil 20 mg once daily for pulmonary artery hypertension. No statistically significant difference was found in hearing threshold at baseline and at follow-up (P > .05). However, three patients on tadalafil 20 mg showed a significant increase in hearing threshold at higher frequencies. There was no incidence of sudden sensorineural hearing loss in the study group. This is the first prospective and observational study that evaluated the effect of tadalafil on auditory functions with objective tests. Although there was no statistically significant result to confirm or refute the association between tadalafil and hearing impairment, increased threshold at higher frequencies after taking tadalafil supports the results from previous studies and hints at a possible relationship between the two. Similar large sample studies are warranted to know the exact association of phosphodiesterase-5 inhibitors on auditory functions.

Effects of Hypertension on Hearing

To determine the likely association between hypertension and hearing loss. 150 cases and 124 controls, both genders, aged 45-64, included in the research after sample estimation. Hypertension was verified through blood pressure readings and was classified as grade 1, grade 2 and grade 3 hypertension or no hypertension according to the blood pressure readings. Hearing was assessed by measuring pure tone threshold at various frequencies ranging between 250 and 8,000Hz. There is a significant association between hypertension and increase in the hearing threshold. Hearing loss in the population under study suggests that hypertension is an accelerating factor of degeneration of the hearing apparatus due to aging. Association between Increased hearing threshold and hypertension in this research, can allow for an integrated work of cardiologists, nephrologists, otorhinolaryngologists, audiologists and other health professionals concerned with alterations caused by hypertension.

Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c‐jun‐N‐terminal kinase signaling

To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM-111. An animal model of cochlear implantation. Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM-111 30 minutes before EIT (EIT+AM-111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)-phalloidin staining for hair cell counts were performed at 90 days post-EIT. Immunostaining for 4-hydroxy-2-nonenal (HNE), activated caspase-3, CellROX, and phospho-c-Jun were performed at 24 hours post-EIT. ABR thresholds increased post-EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM-111 treated or unoperated control ears. AM-111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post-EIT. Immunostaining of 24-hour post-EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase-3 was observed only in SCs, and phosphorylation of c-Jun occurred only in HCs of the EIT-only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase-3, or phospho-c-Jun in the organ of Corti specimens from AM-111 treated cochleae. Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM-111 provided a significant level of protection against EIT-induced hearing losses, HC losses, and damage to neural elements.

A combination of cilostazol and Ginkgo biloba extract protects against cisplatin-induced Cochleo-vestibular dysfunction by inhibiting the mitochondrial apoptotic and ERK pathways

Cisplatin (cis-diammine-dichloroplatinum; CDDP) is an anticancer drug that induces significant hearing loss and balance dysfunction as side effects. Cilostazol (CS, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3, 4-dihydro-2-(1H)-quinolinone) has neuroprotective and antioxidant effects, whereas Ginkgo biloba extract (GbE) has preventive effects on CDDP-induced hearing loss in rats, and GbE enhances the antiatherogenic effect of CS by inhibiting the generation of reactive oxygen species (ROS). The purpose of this study was to investigate the effects of renexin (RXN), which contains GbE and CS, against CDDP-induced cochleo-vestibular dysfunction in rats and to elucidate the mechanism underlying the protective effects of RXN on auditory cells. Rats intraperitoneally injected with CDDP exhibited an increase in hearing threshold and vestibular dysfunction, which agreed with hair cell damage in the Organ of Corti and otoliths. However, these impairments were significantly prevented in a dose-dependent manner by pre- and co-treatment with RXN, and these preventive effects in RXN-treated rats were more prominent than those in GbE-treated rats. In a CDDP pharmacokinetic study, platinum concentration was very similar between CDDP-only treated and RXN+CDDP cotreated rats. RXN markedly attenuated CDDP-induced intracellular ROS and significantly reduced CDDP-activated expression of p-extracellular regulated kinase (ERK), BAX, cytochrome c, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, but increased BCL-XL expression. These results show that RXN may have a synergistic effect by strongly protecting hearing and vestibular dysfunction induced by CDDP by inhibiting ROS production, mitochondrial pathways and the ERK pathway, without interfering with CDDP pharmacokinetics. Therefore, RXN could potentially be used to reduce CDDP-related hearing loss and dizziness.