Photobiomodulation therapy in improvement of harmful neural plasticity in sodium salicylate-induced tinnitus.

Tinnitus is a common annoying symptom without effective and accepted treatment. In this controlled experimental study, photobiomodulation therapy (PBMT), which uses light to modulate and repair target tissue, was used to treat sodium salicylate (SS)-induced tinnitus in a rat animal model. Here, PBMT was performed simultaneously on the peripheral and central regions involved in tinnitus. The results were evaluated using objective tests including gap pre-pulse inhibition of acoustic startle (GPIAS), auditory brainstem response (ABR) and immunohistochemistry (IHC). Harmful neural plasticity induced by tinnitus was detected by doublecortin (DCX) protein expression, a known marker of neural plasticity. PBMT parameters were 808 nm wavelength, 165 mW/cm2 power density, and 99 J/cm2 energy density. In the tinnitus group, the mean gap in noise (GIN) value of GPIAS test was significantly decreased indicated the occurrence of an additional perceived sound like tinnitus and also the mean ABR threshold and brainstem transmission time (BTT) were significantly increased. In addition, a significant increase in DCX expression in the dorsal cochlear nucleus (DCN), dentate gyrus (DG) and the parafloccular lobe (PFL) of cerebellum was observed in the tinnitus group. In PBMT group, a significant increase in the GIN value, a significant decrease in the ABR threshold and BTT, and also significant reduction of DCX expression in the DG were observed. Based on our findings, PBMT has the potential to be used in the management of SS-induced tinnitus.

Self-reporting of hearing loss and tinnitus in the diagnosis of ototoxicity by meglumine antimoniate in patients treated for American tegumentary Leishmaniasis.

INTRODUCTION: American Tegumentary Leishmaniasis (ATL) treatment is based on pentavalent antimonials (Sb5+), but these drugs have been associated to several adverse effects. Hearing loss and tinnitus during treatment with meglumine antimoniate (MA) have already been reported. This study aimed to describe the usefulness of self-reporting of hearing loss and tinnitus in diagnosing MA-induced ototoxicity. METHODS: A prospective longitudinal study was conducted with 102 patients with parasitological diagnosis of ATL, treated with different MA schemes. The presence of clinical auditory toxicity was defined as the emergence or worsening of self-reporting hearing loss and/or tinnitus during monitoring. Measures of sensitivity, specificity, and the positive and negative predictive value of the patient's self-reporting of hearing loss and tinnitus in relation to the result of the audiometric test (considered the gold standard) were calculated. RESULTS: The age of the evaluated patients ranged from 15 to 81 years, with a median of 41 years, and most were male (73.5%). Seventy-five patients (73.5%) had cutaneous leishmaniasis and 27 (26.5%) mucosal leishmaniasis. Eighty-six patients (84.3%) received intramuscular (IM) treatment and 16 (15.7%) were treated with intralesional MA. During treatment, 18 (17,6%) had tinnitus and 7 (6,9%) had complaint of hearing loss. 53 (52%) patients had cochlear toxicity confirmed by tone threshold audiometry and high frequency audiometry, from which 60% received a dose of 20 mg Sb5+/kg/day (p = 0.015) and 96.2% were treated with IM MA (p = 0.001). Tinnitus has greater specificity and positive predictive value than hearing loss, with a low number of false positives, but with a high false negative value. CONCLUSION: Although the large number of false negatives suggests that self-report of hearing loss or tinnitus cannot be considered a good screening test for referring the patient to an audiometry, the low number of false positives suggests the need to value the patient's complaint for referral. Otherwise, this study reinforces the importance of audiological monitoring during treatment with MA, especially in those patients with self-reporting of hearing loss or tinnitus when treated with 20 mg Sb5+/kg/day via IM.

Effectiveness of transcutaneous vagus nerve stimulation (tVNS) on salicylate-induced tinnitus.

INTRODUCTION: Tinnitus is the most common symptom of auditory system disorders. It affects the quality of life of millions of people, but it is still incurable in most cases. Vagus nerve stimulation (VNS) therapy is a potential new treatment for subjective tinnitus. In this study, transcutaneous vagus nerve stimulation (tVNS) combined with tones was utilized to treat salicylate-induced tinnitus since salicylate is a reliable and convenient approach for rapidly inducing tinnitus. METHODS: Wistar rats were divided into acoustic stimulation alone (AS, n = 6), tVNS alone (n = 6), and tVNS with AS (n = 6) groups for behavioral and electrophysiological tests. They were assessed by auditory brainstem response (ABR), prepulse inhibition (PPI), gap prepulse inhibition of the acoustic startle (GPIAS), social interactions, and aggressive behavior tests at baseline and seven days' post-salicylate (175 mg/kg, twice a day) injection. RESULTS: The inhibition percentage of the GPIAS test was significantly reduced post-salicylate injection in the tVNS and AS alone groups, while it was not significant in the tVNS with AS group. There was no significant difference in the mean percentage of the GPIAS test between the tVNS groups (with or without AS) after salicylate injections. Social interactions were significantly different in the AS alone group pre- and post-salicylate injections, but they were not significant in other groups. Moreover, the results of aggressive behavior tests showed significantly increased post-salicylate injections in the AS alone group, while they were not significant in the tVNS groups (with or without AS). CONCLUSIONS: The current study revealed that the application of tVNS alone produced improved social interaction and mood and alleviated salicylate-induced tinnitus severity. Moreover, combining tVNS with acoustic stimulation can prevent salicylate-induced tinnitus.

Online ascorbate sensing reveals oxidative injury occurrence in inferior colliculus in salicylate-induced tinnitus animal model.

Tinnitus is a widespread and serious clinical and social problem. Although oxidative injury has been suggested to be one of pathological mechanisms in auditory cortex, whether this mechanism could be applied to inferior colliculus remains unclear. In this study, we used an online electrochemical system (OECS) integrating in vivo microdialysis with selective electrochemical detector to continuously monitor the dynamics of ascorbate efflux, an index of oxidative injury, in inferior colliculus of living rats during sodium salicylate-induced tinnitus. We found that OECS with a carbon nanotubes (CNTs)-modified electrode as the detector selectively responses to ascorbate, which is free from the interference from sodium salicylate and MK-801 that were used to induce tinnitus animal model and investigate the N-methyl-d-aspartate (NMDA) receptor mediated excitotoxicity, respectively. With the OECS, we found that the extracellular ascorbate level in inferior colliculus significantly increases after salicylate administration and such increase was suppressed by immediate injection of NMDA receptor antagonist MK-801. In addition, we found that salicylate administration significantly increases the spontaneous and sound stimuli evoked neural activity in inferior colliculus and that the increases were inhibited by the injection of MK-801. These results suggest that oxidative injury may occur in inferior colliculus following salicylate-induced tinnitus, which is closely relevant to the NMDA-mediated neuronal excitotoxicity. This information is useful for understanding the neurochemical processes in inferior colliculus involved in tinnitus and its related brain diseases.

Patient-Reported Functional Impairment Due to Hearing Loss and Tinnitus After Cisplatin-Based Chemotherapy.

PURPOSE: Cisplatin is widely used and highly ototoxic, but patient-reported functional impairment because of cisplatin-related hearing loss (HL) and tinnitus has not been comprehensively evaluated. PATIENTS AND METHODS: Testicular cancer survivors (TCS) given first-line cisplatin-based chemotherapy completed validated questionnaires, including the Hearing Handicap Inventory for Adults (HHIA) and Tinnitus Primary Function Questionnaire (TPFQ), each of which quantifies toxicity-specific functional impairment. Spearman correlations evaluated associations between HL and tinnitus severity and level of functional handicap quantified with the HHIA and TPFQ, respectively. Associations between HL or tinnitus and five prespecified adverse health outcomes (cognitive dysfunction, fatigue, depression, anxiety, and overall health) were evaluated. RESULTS: HL and tinnitus affected 137 (56.4%) and 147 (60.5%) of 243 TCS, respectively. Hearing aids were used by 10% TCS (14/137). Of TCS with HL, 35.8% reported clinically significant functional impairment. Severe HHIA-assessed functional impairment was associated with cognitive dysfunction (odds ratio [OR], 10.62; P < .001), fatigue (OR, 5.48; P = .003), and worse overall health (OR, 0.19; P = .012). Significant relationships existed between HL severity and HHIA score, and tinnitus severity and TPFQ score (P < .0001 each). TCS with either greater hearing difficulty or more severe tinnitus were more likely to report cognitive dysfunction (OR, 5.52; P = .002; and OR, 2.56; P = .05), fatigue (OR, 6.18; P < .001; and OR, 4.04; P < .001), depression (OR, 3.93; P < .01; and OR, 3.83; P < .01), and lower overall health (OR, 0.39; P = .03; and OR, 0.46; P = .02, respectively). CONCLUSION: One in three TCS with HL report clinically significant functional impairment. Follow-up of cisplatin-treated survivors should include routine assessment for HL and tinnitus. Use of the HHIA and TPFQ permit risk stratification and referral to audiologists as needed, since HL adversely affects functional status and is the single largest modifiable risk factor for cognitive decline and dementia in the general population.

Prevalence and risk factors for ototoxicity after cisplatin-based chemotherapy.

PURPOSE: Ototoxicity is a prominent side effect of cisplatin-based chemotherapy. There are few reports, however, estimating its prevalence in well-defined cohorts and associated risk factors. METHODS: Testicular cancer (TC) survivors given first-line cisplatin-based chemotherapy completed validated questionnaires. Descriptive statistics evaluated the prevalence of ototoxicity, defined as self-reported hearing loss and/or tinnitus. We compared patients with and without tinnitus or hearing loss using Chi-square test, two-sided Fisher's exact test, or two-sided Wilcoxon rank sum test. To evaluate ototoxicity risk factors, a backward selection logistic regression procedure was performed. RESULTS: Of 145 TC survivors, 74% reported ototoxicity: 68% tinnitus; 59% hearing loss; and 52% reported both. TC survivors with tinnitus were more likely to indicate hypercholesterolemia (P = 0.008), and difficulty hearing (P < .001). Tinnitus was also significantly related to age at survey completion (OR = 1.79; P = 0.003) and cumulative cisplatin dose (OR = 5.17; P < 0.001). TC survivors with hearing loss were more likely to report diabetes (P = 0.042), hypertension (P = 0.007), hypercholesterolemia (P < 0.001), and family history of hearing loss (P = 0.044). Risk factors for hearing loss included age at survey completion (OR = 1.57; P = 0.036), hypercholesterolemia (OR = 3.45; P = 0.007), cumulative cisplatin dose (OR = 1.94; P = 0.049), and family history of hearing loss (OR = 2.87; P = 0.071). CONCLUSIONS: Ototoxicity risk factors included age, cisplatin dose, cardiovascular risk factors, and family history of hearing loss. Three of four TC survivors report some type of ototoxicity; thus, follow-up of cisplatin-treated survivors should include routine assessment for ototoxicity with provision of indicated treatments. IMPLICATIONS FOR CANCER SURVIVORS: Survivors should be aware of risk factors associated with ototoxicity. Referrals to audiologists before, during, and after cisplatin treatment is recommended.

The long-term impacts of hearing loss, tinnitus and poor balance on the quality of life of people living with and beyond cancer after platinum-based chemotherapy: a literature review.

PURPOSE: To elucidate the long-term impacts of hearing loss, tinnitus and balance in people living with and beyond cancer (LWBC) treated with platinum-based chemotherapy (PBCT). METHODS: A literature search was conducted between March and June 2022 using PubMed, Web of Science and Google Scholar. Full-text papers in English were included. Articles explored the impacts of hearing loss, tinnitus and balance and discussed them in the context of treatment. If PBCT was used in conjunction with other treatments, the article was included. There were no constraints on age, cancer type, publication date, location, study design or data type. Sixteen studies and two reviews were included. RESULTS: Hearing loss and tinnitus can cause communication difficulties and subsequent social withdrawal. There were deficits in cognition, child development and educational performance. Employment and the ease of everyday life were disrupted by hearing loss and tinnitus, whereas poor balance interfered with walking and increased the risk of falls. Depression and anxiety were related to ototoxicity. Most notable were the differing mindsets experienced by adults LWBC with ototoxicity. There was evidence of inadequate monitoring of ototoxicity by clinicians and a lack of communication between clinicians and patients about ototoxicity as a side effect. CONCLUSIONS: Ototoxicity has a negative long-term impact on multiple areas of life for adults and children LWBC. This can compromise their quality of life. IMPLICATIONS FOR CANCER SURVIVORS: Increased awareness, monitoring and education surrounding these issues may lead to earlier intervention and better management of ototoxicity, enhancing the quality of life of people LWBC.

Cancer survivors and neurotoxic chemotherapy: hearing loss and tinnitus.

OBJECTIVES: Little is known about hearing loss and tinnitus associated with neurotoxic chemotherapy. Study evaluated for differences in occurrence rates and effects of hearing loss and tinnitus in survivors who received a platinum alone, a taxane alone or a platinum and taxane containing regimen. METHODS: Total of 273 survivors with breast, gastrointestinal, gynaecological or lung cancer completed self-report measures of hearing loss and tinnitus and had an audiometric assessment that obtained pure tone air conduction thresholds bilaterally at frequencies of between 0.25 kHz to 16.0 kHz. To adjust for age-related and gender-related changes in hearing, each survivor's audiogram was evaluated using the National Health and Nutrition Examination Survey-modified Occupational Safety and Health Administration standards. Survivor was classified as having hearing loss if at any frequency they scored poorer than the 50th percentile for their age and gender. Survivors were categorised as having tinnitus if they reported that for >10% of their time awake, they were consciously aware of their tinnitus. Differences among the chemotherapy groups were evaluated using parametric and non-parametric tests. RESULTS: For most of the demographic and clinical characteristics, no differences were found among the three chemotherapy groups. Occurrence rates for audiogram-confirmed hearing loss ranged from 52.3% to 71.4%. Occurrence rates for tinnitus ranged from 37.1% to 40.0%. No differences were found among the three chemotherapy groups in the occurrence rates or effects of hearing loss and tinnitus. CONCLUSION: These findings suggest that regardless of the chemotherapy regimen common mechanistic pathway(s) may underlie these two neurotoxicities.

Risk factors associated with cisplatin-induced ototoxicity in Japanese patients with solid tumors.

BACKGROUND: Cisplatin, a first-generation platinum agent, is used for managing various cancers and is associated with dose-dependent side effects of hearing impairment and tinnitus. However, the safety of high-dose cisplatin in hearing impairment, has not been fully investigated in Japan. METHODS: We performed pure-tone threshold audiometry before and every 3-4 weeks after chemotherapy for patients receiving cisplatin-containing chemotherapy between April 2015 and October 2017 at Kobe Minimally Invasive Cancer Center. Hearing impairment was evaluated prospectively using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: We enrolled 100 patients and analyzed 96 patients for whom post-chemotherapy audiometry could be performed. The median patient age was 65 years, and most patients were male (75). The cancer types were as follows: esophageal, 36; head and neck, 35; lung, 23; and gastric, 2. Cisplatin monotherapy and combination therapy were administered to 33 and 63 patients, respectively. A single cisplatin dose was 60-100 mg/m2 ; the median number of doses and total dose were 3 and 240 mg/m2 , respectively. Additionally, 78 and 18 patients were treated with concurrent chemoradiotherapy and chemotherapy alone, respectively. Twenty-seven patients had grade 2 or higher hearing impairment. Furthermore, the prevalence was significantly higher in patients receiving a total dose of ≥300 mg/m2 . Twenty and 32 patients were aware of deafness and tinnitus, respectively. CONCLUSION: No patient discontinued treatment owing to hearing impairment. The total cisplatin dose was considered related to post-treatment hearing impairment frequency in Japanese patients. However, routine audiometric monitoring is recommended during high-dose cisplatin-based chemotherapy.

Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus.

To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential.

Pharmacogenomics of cisplatin-induced neurotoxicities: Hearing loss, tinnitus, and peripheral sensory neuropathy.

PURPOSE: Cisplatin is a critical component of first-line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin-induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy. METHODS: Utilizing linear and logistic regression analyses on 1680 well-characterized cisplatin-treated testicular cancer survivors, we analyzed associations of hearing loss, tinnitus, and peripheral neuropathy with nongenetic comorbidities. Genome-wide association studies and gene-based analyses were performed on each phenotype. RESULTS: Hearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension and poorer self-reported health. In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork-related noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Hearing loss and TXNRD1, which plays a key role in redox regulation, showed borderline significance (p = 4.2 × 10-6 ) in gene-based analysis. rs62283056 in WFS1 previously found to be significantly associated with hearing loss (n = 511), was marginally significant in an independent replication cohort (p = 0.06; n = 606). Gene-based analyses identified significant associations between tinnitus and WNT8A (p = 2.5 × 10-6 ), encoding a signaling protein important in germ cell tumors. CONCLUSIONS: Genetics variants in TXNRD1 and WNT8A are notable risk factors for hearing loss and tinnitus, respectively. Future studies should investigate these genes and if replicated, identify their potential impact on preventive strategies.

[Susceptibility and mechanism of sodium salicylate-induced tinnitus model in low estrogen rats].

Objective: The susceptibility of tinnitus rats with low estrogen level induced by sodium salicylate and the changes of tumor necrosis factor α (TNF-α) in serum were observed to investigate the relationship between tinnitus occurrence and estrogen level. Methods: Forty-two healthy female Wistar rats were randomly divided into control group(n=6), normal group(n=6), sham operation group(n=6) and ovariectomized group(n=24). Control group was intraperitoneally injected with normal saline 200 mg/kg for 14 consecutive days. Normal group, sham operation group and ovariectomized group were intraperitoneally injected with sodium salicylate 200 mg/kg for 14 consecutive days. Before and after sodium salicylate induction, the tinnitus behavior of rats in each group was detected by prepulse inhibition (PPI) and gap pre-pulse inhibition of the acoustic startle (GPIAS) test. Before and after sodium salicylate induction, blood samples were collected from eyeballs of rats in each group, and serum levels of estradiol and TNF-α were detected by ELISA. SPSS 25.0 software was used to analyze the data. Results: (1) Following 14 days of sodium salicylate intervention, there was no significant difference in PPI inhibition rate between groups or within groups(all P>0.05). (2)There was no significant difference in the inhibition rate of GPIAS in the four groups before sodium salicylate injection(F=0.217, P>0.05). With sodium salicylate injected for 14 days, the inhibition rate of GPIAS in ovariectomized group (30.88%±15.40%) was significantly lower than that in the other three groups (44.11%±21.06%, 38.27%±10.92%, 51.59%±11.34%), and the difference was statistically significant(F=3.533, P<0.05). The inhibition rate of GPIAS in ovariectomized group with sodium salicylate injected for 14 days was significantly lower than that before injection, and the difference was statistically significant(t=2.977, P<0.05).There was no significant difference in GPIAS inhibition rate between the other three groups before and after sodium salicylate injection(P>0.05). (3)The level of TNF-α in ovariectomized rats was significantly higher than that in the other three groups, the difference was statistically significant(all P<0.05). With sodium salicylate injection for 14 days, TNF-α level in the ovariectomized group increased more significantly than that in the other three groups, the difference was statistically significant(F=8.045, P<0.05). TNF-α levels increased following salicylate injection in normal group, sham operation group and ovariectomized group, and the differences were statistically significant(t value was -4.843, -4.932 and -5.965 respectively, each P<0.05). There was no significant difference in TNF-α levels before and after normal saline injection in control group(all P>0.05). Conclusion: Low estrogen levels increase susceptibility to sodium salicylate-induced tinnitus. Decreased estrogen levels may increase susceptibility to tinnitus through the increased expression of pro-inflammatory factor TNF-α.

Proton pump inhibitor use and hearing loss in patients with type 2 diabetes: Evidence from a hospital-based case-control study and a population-based cohort study.

OBJECTIVES: This study aimed to investigate the association between proton pump inhibitor (PPI) use and risk of sensorineural hearing loss (SNHL) or tinnitus in patients with type 2 diabetes using hospital- and population-based data. METHODS: For the case-control study using the Asan Biomedical Research Environment database, the characteristics between cases and sex-, age- and index-year-matched controls were compared by the chi-squared test. Conditional logistic regression was used to estimate the odds ratios (ORs). For the cohort study using the Korean National Health Insurance Service - National Sample Cohort, the hazard ratios (HRs) for SNHL or tinnitus associated with PPI use were analysed by the Cox proportional hazard regression model. RESULTS: The case-control study included 1379 cases and 5512 matched controls. After adjustment, PPI use was associated with an increased risk of SNHL or tinnitus (OR 1.61, 95% confidence interval [CI] 1.30-1.99). The ORs were higher for current or recent use of PPI and high average daily dose. In the cohort study including 17 233 pairs of PPI users and nonusers after propensity score matching, the risk of SNHL or tinnitus increased in PPI users compared with nonusers (HR 1.50, 95% CI 1.40-1.61). In the stratified analyses, risks remained significant and the magnitude of association was relatively high in those of younger age, patients without gastroesophageal reflux disease and patients not receiving histamine 2 receptor blockers. CONCLUSIONS: Our study suggests that PPI use is associated with an increased risk of SNHL or tinnitus. Given the widespread use of PPIs, the potential ototoxic effects of PPIs remain an important concern.

Development of ebselen for the treatment of sensorineural hearing loss and tinnitus.

The global impact of hearing loss and related auditory dysfunction including tinnitus and hyperacusis on human health is significant and growing. A substantial body of literature has found that these hearing diseases and disorders result from significant number of genetic variations and molecular mechanisms. Investigational new drugs have been tested and several approved drugs have been repurposed in clinical trials, but no therapeutics for any auditory related indication have been FDA approved. A unique investigational new drug called ebselen (SPI-1005), that is anti-inflammatory and neuroprotective, has been shown to reduce noise-induced and aminoglycoside-induced hearing loss in animals. Multiple phase 2 clinical trials have demonstrated the safety and efficacy of SPI-1005 treatment in Meniere's disease and acute noise-induced hearing loss. SPI-1005 is currently being tested to prevent and treat tobramycin-induced ototoxicity in cystic fibrosis patients with acute lung infections. This review summarizes the published and presented data involving SPI-1005 and other drugs being tested to prevent or treat sensorineural hearing loss. Additionally, recent clinical data showing the relationship between pure tone audiometry and words-in-noise test results in a Meniere's disease are presented, which may have larger implications for the field of hearing research.

Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation.

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

The impact of chemotherapy-induced inner ear damage on quality of life in cancer survivors: a qualitative study.

PURPOSE: This study aimed to explore the burden of inner ear damage (ototoxicity) on adults living with and beyond cancer treated with chemotherapy and  the impact on their quality of life (QoL). Furthermore, this study aimed to explore patient awareness surrounding chemotherapy-induced inner ear damage, known as ototoxicity, and assess what support they had been offered. METHODS: Participants were adults who had undergone chemotherapy, recruited from cancer clinics, charities and social media. Using semi-structured interviews and fieldnotes, an inductive thematic analysis was used to develop key themes surrounding this topic. RESULTS: Twenty participants from the UK were interviewed. Two key themes were developed from the thematic analysis, cancer-related QoL and ototoxicity-related QoL, with each one including 5 subthemes. Subthemes consisted of impact of ototoxicity, hearing, tinnitus, clinical experience, audiological assessments, and impact of treatment, cancer and chemotherapy, other toxicities, information and patient reflections. CONCLUSIONS: Ototoxicity can have a negative impact on QoL, specifically on social life and the fear of hearing loss and/or tinnitus worsening. There are opportunities for increased awareness by patients and clinicians, including improved information sources, and hearing monitoring not only for those undergoing platinum-based chemotherapy but many others surviving after treatment for cancer. IMPLICATIONS FOR CANCER SURVIVORS: Better monitoring of hearing and information about ototoxicity during chemotherapy could potentially reduce the fear of the symptoms of ototoxicity worsening. Furthermore, hearing monitoring would facilitate the detection of hearing loss at early stages of survivorship, which would facilitate earlier access to clinical interventions and longer term counselling.

Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation / 神经科学通报·英文版

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

Los acúfenos de Miguel Ángel y su relación con la toxicología / Miguel Ángel's tinnitus and its relation to toxicology

Resumen El Plomo ha tenido una estrecha relación con el mundo artístico pictórico a través de los pigmentos utilizados por los artistas durante milenios. El íntimo contacto con sustancias químicas potencialmente peligrosas para la salud, casi siempre sin medidas de higiene y seguridad laboral, ha desarrollado en muchos casos, enfermedades laborales en estos artistas, a veces sospechadas y en otros casos, más que confirmadas. En el presente trabajo se analiza la historia de vida laboral de Miguel Angel Buonarroti, de quien se tiene registro suficiente como para establecer un nexo causal con exposición laboral al Plomo.

Abstract Lead has shown a close relationship with the fine arts'world through the pigments used by artists for thousand of years. Close contact with potentially dangerous chemical substances for health, almost always without occupational hygiene and safety measures, has produced, in many cases, occupational illnesses in these artists, sometimes suspected and in other cases, more than confirmed. In the present work, the history of Miguel Angel Buonarroti's working life is analyzed, since there is sufficient record to establish a causal link with occupational exposure to Lead.

Drug-induced diseases in otolaryngology - causes, clinical signs, treatment.

In the daily practice of an otolaryngologist, we encounter cases where the symptoms are not the result of disease but result from pharmacotherapy. In the case of symptoms such as hearing loss, tinnitus, or dizziness, polytherapy may be used as the basis for their occurrence, which, due to the lack of rationality in combining drugs, leads to symptoms that the patient and the doctor very often interpret as a new disease syndrome. The aim of the study is to show and to raise awareness of the fact that the symptoms of hearing organ impairment are frequently drug-related and only a modification of the currently used pharmacotherapy is a rational procedure in such cases. This paper describes 30 cases who developed side effects of polypharmacy in the form of hearing disorders, dizziness, and tinnitus. The causes of drug-related complications were discussed, as well as effective methods of their prevention.