The role of vitamin D in subjective tinnitus-A case-control study.

Regarding the high prevalence of vitamin D (25(OH)D) deficiency in the population and its possible association with ear diseases, we aimed to investigate the 25(OH)Dserum level in patients with subjective, nonpulsating tinnitus and its effect on tinnitus severity. The study included 201 tinnitus patients and 99 controls. Patient clinical information, including tinnitus characteristics and severity according to Tinnitus Handicap Inventory (THI), loudness assessed by Visual Analogue Scale (VAS), audiometry, and the blood level of vitamin D, was recorded. The level of 25(OH)D in tinnitus patients was significantly decreased compared with the controls (19.86 ± 7.53 and 27.43 ± 8.85 ng/ml, respectively; P value < 0.0001). More patients in the tinnitus group were deficient in vitamin D, compared with the controls (50.7% vs. 22.2% respectively, p < 0.0001). Tinnitus patients with a lower serum level of 25(OH)D (≤15 ng/dl) were significantly younger, had a higher degree of tinnitus severity measured with THI and VAS scales, had higher triglyceride and TSH levels, and a lower HDL level compared with individuals who had higher 25(OH)D level (>15 ng/dl). There was a strong correlation between the 25(OH)D level and THI. Our findings suggest that a large proportion of tinnitus patients suffers from vitamin D deficiency and that the vitamin D level correlates with tinnitus impact. We recommend a vitamin D assessment for all tinnitus patients.

The Effect of Natural Ocean Sound Exposure and Ocean-Side Relaxation on Chronic Tinnitus Patients: A Pilot Study in Korea.

Sound therapy is a treatment modality for tinnitus patients by increasing the background neuronal activity in the auditory system and inducing relative alleviation of the tinnitus. This study was performed to evaluate the efficacy of natural ocean sound exposure and ocean-side relaxation in chronic tinnitus patients. We prospectively enrolled all 18 chronic tinnitus patients (≥6 months) from July to November 2018. All patients completed 90 hours of our programs. The improvement in their subjective tinnitus severity, moods, the quality of life, and sleep was serially assessed using several questionnaires at baseline, immediately, and 1 month after the program. Changes in serum stress hormone levels of the patients were also compared between the baseline and immediately after the program. Average total Tinnitus Handicap Questionnaire score and factor 2 (hearing difficulty related to tinnitus) score significantly improved over time (P = .024 and P = .002). Patient's serum cortisol and epinephrine level did not show significant decrease, and serum norepinephrine and serotonin level significantly increased immediately after our program (P < .001 and P < .001). Natural ocean sound exposure and ocean-side relaxation for short-term period has a potential efficacy on chronic tinnitus patients.

Increased platelet activity in tinnitus patients.

OBJECTIVE: The aim of our study was to establish whether or not tinnitus patients have higher platelet activity, as measured by plasma 11-dehydro-thromboxane B2 levels, compared with individuals without tinnitus. METHODS: The study group included patients without documented organic causes of tinnitus or a cause of non-vascular hearing impairment. Laboratory tests included complete blood count, biochemistry, coagulation activity, and thromboxane levels. To exclude a pathology in the cerebellopontine angle, CT and MRI were performed together with an X-ray scan of cervical vertebrae. For the purpose of this study, blood samples were screened for 11-dehydro-thromboxane B2 levels using commercial kits. RESULTS: A comparison of the main marker of increased platelet activity i.e., thromboxane levels of tinnitus patients with those of a control group, showed increased thromboxane levels in the former. The average plasma concentrations of 11-dehydro-thromboxane B2 were 2.0234±1.80 ng/ml in the group of tinnitus patients and 1.3247±1.33 ng/ml in the control group. Our results showed that patients with tinnitus have significantly higher values of 11-dehydro-thromboxane B2. CONCLUSION: Tinnitus patients showed higher levels of increased platelet activity, a marker that may play an important role in the pathogenesis of tinnitus.

Proteasome Activity in the Plasma as a Novel Biomarker in Mild Cognitive Impairment with Chronic Tinnitus.

BACKGROUND: Although the existence of proteasomes in human blood, termed circulating proteasomes (c-proteasomes), has been reported previously, their origin and pathophysiological functions remain largely unknown. OBJECTIVE: Given that c-proteasome activity was significantly reduced in Alzheimer's disease model mice and relatively high frequency of mild cognitive impairment (MCI) is accompanied by chronic tinnitus in aged patients, we examined whether c-proteasome activity in human plasma was associated with cognitive function in patients with chronic tinnitus. METHODS: c-Proteasome activity in the plasma of tinnitus patients (N = 55) was measured with fluorogenic reporter substrate, suc-LLVY-AMC. To assess MCI, the Montreal Cognitive Assessment was conducted with a cut-off score of 22/23. All patients underwent audiological and psychoacoustic analyses. Levels of c-proteasomes, Aß42, and Aß40 were measured using ELISA, and their association with c-proteasome activity was evaluated. RESULTS: The activity of circulating proteasomes was significantly lower in patients with chronic tinnitus and MCI (p = 0.042), whereas activities of other plasma enzymes showed little correlation. In addition, c-proteasome activity was negatively associated with the level of plasma Aß and was directly dependent on its own concentration in the plasma of patients with chronic tinnitus. CONCLUSION: Our current work provides a new perspective for understanding the potential relationship between circulating proteasomes in the plasma and cognitive dysfunction, suggesting a novel, non-invasive biomarker in the context of MCI diagnosis.

Tinnitus, hearing loss and inflammatory processes in an older Portuguese population.

Objective: Tinnitus is associated with various conditions such as presbycusis, infectious, autoimmune and many other diseases. Our study aims to identify an association between inflammatory markers and the presence of tinnitus or hearing loss (HL).Design: Exploratory study including a structured interview, complete ENT observation, audiological and inflammatory markers evaluation.Study Sample: Sixty women and 54 men (55 to 75 years) from the Portuguese population, with or without sensory presbycusis and/or tinnitus.Results: IL10 levels were significantly lower in participants with tinnitus than in those without tinnitus. Moreover, TGF-ß was lower in older participants (p = 0.034), IL1α was higher in participants with tonal tinnitus (p = 0.033), and IL2 was lower in participants who reported partial or complete residual inhibition (p = 0.019). Additionally, we observed a negative correlation between tinnitus duration and IL10 levels (r= -.281), and between HSP70 levels and tinnitus loudness (r= -.377). TNF-α and HSP70 levels appears to be sensitive to the time when samples were collected (morning or afternoon).Conclusions: The results of our study showing fluctuations in inflammatory markers along the hearing loss process, reinforce the idea that inflammatory mechanisms are involved in hearing loss pathogenesis but also in tinnitus. IL10 levels appear significantly altered in tinnitus but not in hearing loss.

The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial.

Tinnitus is the perception of sound in the absence of any external stimulus. Oxidative stress is possibly involved in its pathogenesis and a variety of antioxidant compounds have been studied as potential treatment approaches. The objective of the present study was to assess the effects of antioxidant supplementation in tinnitus patients. This is a randomized, double-blind, placebo-controlled clinical trial. Patients (N = 70) were randomly allocated to antioxidant supplementation (N = 35) or to placebo (N = 35) for a total of 3 months. Demographic, anthropometric, clinical, and nutritional data were collected. Serum total antioxidant capacity (TAC), oxidized LDL (oxLDL), and superoxide dismutase (SOD), tinnitus loudness, frequency, and minimum masking level (MML), and scores in Tinnitus Handicap Inventory questionnaire (THI), Tinnitus Functional Index (TFI), and Visual Analogue Scale (VAS) were evaluated at baseline and follow-up. Tinnitus loudness and MML significantly decreased from baseline to post measure (p < 0.001) only in the antioxidant group, the overall change being significantly different between the two groups post-intervention (p < 0.001). THI and VAS decreased only in the antioxidant group. Differences in changes in serum TAC, SOD, and oxLDL post-intervention were insignificant. In conclusion, antioxidant therapy seems to reduce the subjective discomfort and tinnitus intensity in tinnitus patients.

The relationship of high-frequency distortion product otoacoustic emission (DPOAE) values with hematological parameters in tinnitus patients.

PURPOSE: In this study, we aimed to investigate whether there is any positive or negative correlation between high-frequency distortion product otoacoustic emission (DPOAE) values and mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR) in tinnitus patients. METHODS: The study was performed with 52 volunteers (27 females, 25 males) aged between 35 and 50 years who presented with tinnitus to the otolaryngology outpatient clinic of a tertiary care center. Pure voice audiometric examination, DPOAE measurement, complete blood count values of the study participants were examined. RESULTS: In both ears, a significant and negative correlation was observed between 4000 and 8000 Hz airway and 4000 Hz bone conduction pathways with NLR rates (p < 0.05). A statistically significant relationship was found between the bone conduction pathway PTA and discrimination values for both ears and NLR s (p < 0.05). A positive correlation was detected between NLRs and DPOAE measurements recorded at 4444 Hz, 5000 Hz, 8000 Hz, 8889 Hz, 10,000 Hz and 11,429 Hz frequencies in the right and 4444 Hz, 5000 Hz, 6154 Hz, 8000 Hz, 10,000 Hz and 11,429 Hz frequencies in the left ears, respectively (p < 0.05). CONCLUSIONS: We concluded that there is a significant correlation between high-frequency pure tone audiometry measurements and high frequency DPOAE measurements and NLR. Further studies are needed to determine the utility of NLR as a marker for the recognition and follow-up of hearing loss in patients with tinnitus.

Can apelin play a role in the etiology of tinnitus?

Background/aim: Tinnitus is seen in 15% of the general population; in 1%­6% of this number, the quality of life is seriously affected by this chronic condition. Chemical, oxidative, and emotional stressors are important in terms of the clinical course of tinnitus. Apelin is an endogenous peptide which is an oxidative stress mediator. It has been shown that the apelin/APJ (apelin junction receptor) system plays various roles in the physiology and pathophysiology of many organs. However, the role of the apelin/APJ system as an oxidative stress mediator in tinnitus is unknown. We investigated the level of apelin in patients with normal hearing and bilateral tinnitus. Materials and methods: We enrolled patients diagnosed with bilateral idiopathic tinnitus. Tinnitus severity was determined using the tinnitus handicap inventory (THI). We recorded the levels of plasma apelin-13 and biochemical parameters. Results: The mean apelin level of the control group was higher than that of the patient group (P = 0.002). A significant negative correlation was evident between the apelin level and the THI (r = ­0.460, P = 0.003). The triglyceride (TG) level was significantly higher in the patient group than in the control group (P < 0.001). Conclusion: In our study, we found a negative correlation between apelin and tinnitus severity. Thus, apelin may play a role in the pathophysiology of idiopathic tinnitus, and may be prescribed during follow-up to reduce oxidative stress in the future. Further clinical studies on the effects of the apelin/APJ (apelin junction receptor) system and the effects of antioxidants in patients with inflammatory diseases are required.

Investigation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and mean platelet volume in patients with tinnitus.

OBJECTIVE: This study aimed to evaluate patients with tinnitus in terms of mean platelet volume and platelet distribution width, and to explore neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, recently reported in the literature as being possible inflammation markers. METHODS: This study comprised 64 tinnitus patients and 64 age-matched healthy controls. Statistical significance level was accepted as p < 0.05. RESULTS: Mean platelet volume (t = 3.245, p = 0.002) and platelet distribution width (Z = 3.945, p < 0.001) were significantly higher in the patient group than the control group. CONCLUSION: The results suggest that a prothrombotic condition might play a role in the pathophysiology of tinnitus.

Exploring pathogenesis in subjects with subjective Tinnitus having kidney deficiency pattern in terms of Traditional Chinese Medicine based on serum metabolic profiles.

OBJECTIVE: To investigate the metabolic pathogenesis in subjects with subjective tinnitus (ST) having kidney deficiency pattern (KDP) (ST/KDP) in terms of Traditional Chinese Medicine. METHODS: Three groups of subjects, including healthy individuals, subjects with ST/KDP, and subjects who were healthy initially and then developed ST/KDP one year later (healthy ¡ú ST/KDP), were recruited for this study. Serum metabolic profiles of all subjects were analyzed using ultra-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry. The metabolic characteristics of the ST/KDP subjects were determined, and the corresponding biomarkers were predicted. The metabolomics data from the healthy ¡ú ST/KDP subjects were collected for further verification. RESULTS: Twelve metabolites in the ST/KDP subjects were different from those of the healthy control subjects. Of these metabolites, according to the prediction, except for octanoic acid, other metabolites might characterize ST/KDP. Ten metabolites at the outcome ST/KDP stage were different from those at the initial (control) stage. Through the comparison of these metabolites with the predicted metabolites, five common metabolites, including upregulated glutamate, serotonin, orotic acid and 8-oxoguanine, as well as downregulated taurine, were found. These common metabolites were significantly associated with canonical pathways including calcium signaling, ¦Ã-aminobutyric acid (GABA) receptor signaling, purine and pyrimidine biosynthesis, taurine biosynthesis, and serotonin receptor signaling. CONCLUSION: The metabolic pathogenesis in ST/KDP subjects was characterized by upregulated glutamate, serotonin, orotic acid and 8-oxoguanine, as well as downregulated taurine, additionally, perturbations of calcium signaling, GABA receptor signaling, purine and pyrimidine biosynthesis, taurine biosynthesis, and serotonin receptor signaling.

Evidence of associations between brain-derived neurotrophic factor (BDNF) serum levels and gene polymorphisms with tinnitus.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) gene polymorphisms are associated with abnormalities in regulation of BDNF secretion. Studies also linked BDNF polymorphisms with changes in brainstem auditory-evoked response test results. Furthermore, BDNF levels are reduced in tinnitus, psychiatric disorders, depression, dysthymic disorder that may be associated with stress, conversion disorder, and suicide attempts due to crises of life. For this purpose, we investigated whether there is any role of BDNF changes in the pathophysiology of tinnitus. MATERIALS AND METHODS: In this study, we examined the possible effects of BDNF variants in individuals diagnosed with tinnitus for more than 3 months. Fifty-two tinnitus subjects between the ages of 18 and 55, and 42 years healthy control subjects in the same age group, who were free of any otorhinolaryngology and systemic disease, were selected for examination. The intensity of tinnitus and depression was measured using the tinnitus handicap inventory, and the differential diagnosis of psychiatric diagnoses made using the Structured Clinical Interview for Fourth Edition of Mental Disorders. BDNF gene polymorphism was analyzed in the genomic deoxyribonucleic acid (DNA) samples extracted from the venous blood, and the serum levels of BDNF were measured. One-way analysis of variance and Chi-squared tests were applied. RESULTS: Serum BDNF level was found lower in the tinnitus patients than controls, and it appeared that there is no correlation between BDNF gene polymorphism and tinnitus. CONCLUSIONS: This study suggests neurotrophic factors such as BDNF may have a role in tinnitus etiology. Future studies with larger sample size may be required to further confirm our results.

Circulating steroids negatively correlate with tinnitus.

While not a disease entity in itself; symptoms of tinnitus (from Latin tinnio - clink) accompany a number of diseases. Tinnitus prevalence increases with age, deteriorates one's quality of life, and may even result in suicidal behavior. Tinnitus develops in response to a variety of risk factors, otoxic substances, noise exposure, hearing disorders, and psychological alterations. Tinnitus is closely related to mood, depression, and psychological state. In the present study, we focused on alterations of the steroid metabolome and particularly neuroactive, neuroprotective, and immunomodulatory steroids in patients with tinnitus. The study group consisted of 28 patients without evidence of an organic cause of tinnitus as well as without associated diseases or the effect of ototoxic medications. All patients underwent a complete audiological assessment and laboratory tests including routine biochemical markers and quantification of circulating steroids using gas chromatography/mass spectrometry and immunoassays. To rule out a pathology in the cerebellopontine angle area, CT scan or MRI were performed. To diagnose stem lesions, evoked potentials were also measured. Pearson's correlations and multivariate regression were used to assess any links between tinnitus intensity and frequency on the one hand, and steroid levels on the other. Results indicated a significant and consistent negative correlation between tinnitus indices and intensity of adrenal steroidogenesis. The circulating steroid metabolome including hormones and neuroactive, neuroprotective, and immunomodulatory steroids negatively correlates with the degree of tinnitus due to hypothalamo-pituitary-adrenal axis malfunction. Our results may help explain the pathophysiology of tinnitus and improve its diagnosis. However, further studies are needed to verify our postulation.

Tinnitus and hyperacusis: Contributions of paraflocculus, reticular formation and stress.

Tinnitus and hyperacusis are common and potentially serious hearing disorders associated with noise-, age- or drug-induced hearing loss. Accumulating evidence suggests that tinnitus and hyperacusis are linked to excessive neural activity in a distributed brain network that not only includes the central auditory pathway, but also brain regions involved in arousal, emotion, stress and motor control. Here we examine electrophysiological changes in two novel non-auditory areas implicated in tinnitus and hyperacusis: the caudal pontine reticular nucleus (PnC), involved in arousal, and the paraflocculus lobe of the cerebellum (PFL), implicated in head-eye coordination and gating tinnitus and we measure the changes in corticosterone stress hormone levels. Using the salicylate-induced model of tinnitus and hyperacusis, we found that long-latency (>10 ms) sound-evoked response components in both the brain regions were significantly enhanced after salicylate administration, while the short-latency responses were reduced, likely reflecting cochlear hearing loss. These results are consistent with the central gain model of tinnitus and hyperacusis, which proposes that these disorders arise from the amplification of neural activity in central auditory pathway plus other regions linked to arousal, emotion, tinnitus gating and motor control. Finally, we demonstrate that salicylate results in an increase in corticosterone level in a dose-dependent manner consistent with the notion that stress may interact with hearing loss in tinnitus and hyperacusis development. This increased stress response has the potential to have wide-ranging effects on the central nervous system and may therefore contribute to brain-wide changes in neural activity.

The Role of Trace Elements in Tinnitus.

In this study, we aimed to investigate the role of three trace elements, namely, zinc, copper, and lead, in tinnitus by analyzing the serum level of copper and lead and both the serum and tissue level of zinc. Eighty patients, who applied to outpatient otolaryngology clinic with the complaints of having tinnitus, and 28 healthy volunteers were included. High-frequency audiometry was performed, and participants who had hearing loss according to the pure tone average were excluded; tinnitus frequency and loudness were determined and tinnitus reaction questionnaire scores were obtained from the patients. Of all the participants, serum zinc, copper, and lead values were measured; moreover, zinc levels were examined in hair samples. The levels of trace elements were compared between tinnitus and control groups. The level of copper was found to be significantly lower in the tinnitus group (p = 0.02), but there was no significant difference between the groups in terms of the levels of zinc, neither in serum nor in hair, and lead in serum (p > 0.05). The lack of trace elements, especially that of "zinc," have been doubted for the etiopathogenesis of tinnitus in the literature; however, we only found copper levels to be low in patients having tinnitus.

Relationship between serum magnesium level and subjective tinnitus.

OBJECTIVES: This study aims to assess the relationship between serum magnesium level and bilateral subjective tinnitus. PATIENTS AND METHODS: The study included a total of 76 patients (36 males, 40 females; mean age 48.5±6.5 years; range 43 to 65 years) suffering from severe bilateral subjective tinnitus (accepted as severe and catastrophic according to tinnitus severity index) as the study group and 86 healthy participants (42 males, 44 females; mean age 43.8±7.3 years; range 40 to 61 years) as the control group. Serum magnesium levels of both groups were measured and compared statistically. RESULTS: The serum magnesium concentration was significantly lower in the study group compared to the control group (1.8±0.2 vs. 2.3±0.4 mg/dL, p=0.03). CONCLUSION: The significant association between serum magnesium level and tinnitus shows the importance of magnesium in the pathophysiology of subjective tinnitus.

Can Platelet Indices Be New Biomarkers for Subjective Tinnitus?

OBJECTIVES: Mean platelet volume (MPV) is one of the platelet function indices that reflect the platelet production rate and functions. The MPV levels are increased by vascular occlusion, acute or chronic syndromes, and vasculitis, whereas infections, autoimmune diseases, and inflammatory situations reduce these levels. In this study, the authors investigated whether there was a relationship between platelet indices and subjective tinnitus. METHODS: In this retrospective study, the authors evaluated platelet indices in subjective tinnitus patients. One hundred patients with subjective tinnitus and 100 healthy, age and sex-matched subjects were enrolled to the study. Audiometer and laboratory results were recorded. Comparative multivariate analyses between indicator factors and hearing outcomes were conducted. RESULTS: Mean platelet volume is significantly lower in subjective tinnitus group (P < 0.001). Platelet count and platelet distribution width are higher in the subjective tinnitus than control group (P < 0.001, P < 0.003, respectively). CONCLUSION: The authors' findings indicate that subjective tinnitus appears to be characterized by autoimmune and inflammatory events. Considering the decreasing MPV levels, MPV may be used to evaluate subjective tinnitus as an helper indicator.

Plasma brain-derived neurotrophic factor levels are increased in patients with tinnitus and correlated with therapeutic effects.

Tinnitus is the perception of sound without an external source and is known to be associated with altered neuronal excitability in the auditory system. Tinnitus severity can be assessed by various psychometric instruments and there is no objective measures developed to evaluate tinnitus severity and therapeutic effects so far. Brain-derived nerve growth factor (BDNF) is believed in playing a key role in regulating neuronal excitability in the brain. To determine whether BDNF correlates with tinnitus induction and severity, we described plasma BDNF levels in patients with tinnitus and healthy controls and evaluated the correlation between plasma BDNF levels and tinnitus severity measured by Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Moreover, alteration of plasma BDNF levels before and after tinnitus retraining therapy (TRT) in patients with severe tinnitus was also analyzed. We found plasma BDNF levels were elevated in patients with tinnitus compared with healthy controls. In addition, plasma BDNF levels in patients with severe tinnitus were decreased significantly after effective TRT. However, plasma BDNF levels were not correlated with tinnitus loudness and tinnitus severity measured by THI and VAS. These findings support plasma BDNF as a marker for activity changes in the auditory system and could possibly evaluate therapeutic effects in patients with tinnitus.

Increased mean platelet volume in patients with idiopathic subjective tinnitus.

Tinnitus is the perception of sound with no external stimulus and idiopathic subjective tinnitus is the most common type in adults. Mean platelet volume (MPV) alterations were shown in some inflammatory diseases and were evaluated as a clinically useful marker. Our aim was to investigate MPV alterations in idiopathic subjective tinnitus patients. A total of 101 patients and 54 age- and sex-matched healthy control subjects were enrolled in the study. Patients included in the study had complaints of tinnitus for at least 3 months. All patients underwent detailed otolaryngologic examination, blood sampling, pure tone audiometry, magnetic resonance imaging of ear, and vertebrobasilar artery Doppler ultrasonography to make the differential diagnosis of tinnitus. Blood sampling consisted of renal-liver-thyroid function tests, lipid profile, and complete blood count. All tests and examinations except the imaging modalities were also performed for the control group. There were no differences in age and sex distribution of groups. Mean platelet volume values were significantly increased in tinnitus patients when compared with controls (p = 0.001). We think that MPV can be qualified as a useful marker in tinnitus patients.

Prognostic value of mean platelet volume on tinnitus.

OBJECTIVE: This study aimed to determine whether there was any relationship between tinnitus and mean platelet volume. METHODS: This retrospective study was conducted between January 2013 and January 2014 in Ankara Atatürk Hospital and Ondokuz Mayis University Hospital, Turkey, on a study group of 86 patients with tinnitus and a control group of 84 healthy subjects. Mean platelet volume was recorded and comparisons were made between the two groups. RESULTS: Mean (± standard deviation) platelet volume was 7.67 ± 0.83 µm(3) in the study group and 7.28 ± 0.56 µm(3) in the control group. There was a statistically significant difference in mean platelet volume between the tinnitus patients and the healthy subjects (p < 0.05). CONCLUSION: The clinical findings indicated that tinnitus patients had a higher mean platelet volume than the healthy control subjects; however, the pathophysiological mechanism remains unclear.

Prestin as a biochemical marker for early detection of acquired sensorineural hearing loss.

Acquired sensorineural hearing loss and tinnitus can come about through various etiologies such as exposure to excessively loud noise or drugs with ototoxic properties. As such, acquired hearing loss is a common source of morbidity which deleteriously affects the ability to communicate. At present our ability to detect acquired hearing loss and tinnitus at its earliest stages is limited and there are no adjuncts to audiometric evaluation. The earliest cellular targets of noise and ototoxins in the cochlea are the outer hair cells (OHC). I hypothesize that serum assays of OHC specific protein, prestin, will allow detection and quantification of OHC damage before audiometric testing can identify presence of hearing loss. At present, there are no data available to evaluate this hypothesis, but initial evaluation can readily be carried out using existing experimental animal models of ototoxicity and noise-induced hearing loss. Early detection of OHC damage is critical to adoption of measures aimed at ameliorating hearing loss and tinnitus, thus reducing permanent deficits and disability.