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.

The importance of audiometric monitoring in patients with multidrug-resistant tuberculosis

Abstract INTRODUCTION: A total of 771 cases of multidrug-resistant tuberculosis (MDR-TB) were reported in Brazil in 2014. Treatment of MDR-TB with aminoglycosides can produce serious side effects such as permanent and irreversible hearing loss, which occurs in 5-64% of cases, and severely compromise patient quality of life. The goal of this research was to evaluate auditory and vestibular side effects in patients treated for MDR-TB and to identify associations between these complaints and the type of aminoglycoside used. METHODS: We performed a retrospective review of 599 medical records from patients with MDR-TB who were treated at the Hélio Fraga/Fiocruz Reference Center between 2006 and 2010. Cases without auditory or vestibular complaints and patients who were not treated with aminoglycoside drugs were excluded from the study. RESULTS: Of 164 eligible cases, 55 (33.5%) reported an auditory or vestibular complaint and medication was subsequently suspended, although hearing damage was not confirmed in all cases. Audiometric testing confirmed hearing loss in 11 (21.7%) of 12 cases submitted for evaluation. Hearing loss related to ototoxicity was confirmed in 15 (62.5%) cases. Tinnitus was significantly associated with the use of amikacin and streptomycin. CONCLUSIONS: Evaluations of ototoxicity symptoms were not usually reported in the routine care of patients with MDR-TB. Complaints of tinnitus were associated with amikacin and streptomycin use. These results require confirmation in future studies.

Cancer treatment in determination of hearing loss / Tratamento oncológico na determinação das alterações auditivas

ABSTRACT INTRODUCTION: Chemotherapy and radiotherapy in oncology have repercussions in hearing health, and can damage structures of the inner ear. These repercussions usually, result in a bilateral and irreversible hearing loss. OBJECTIVE: To identify sensorineural hearing loss cases with complaints of tinnitus and difficulty in speech understanding and investigate their relationship with the types of chemotherapy and radiotherapy the patients received. METHODS: Cross-sectional, clinical, observational, analytical, historical cohort study of 58 subjects treated in a public hospital in the state of Sergipe, diagnosed with neoplasia. The subjects were submitted to anamnesis, conventional pure tone audiometry, and speech recognition threshold. RESULTS: Of the 116 ears, 25.9% presented sensorioneural hearing loss characterized by changes in high frequencies. There was a positive correlation between hearing loss and the association of chemotherapy and radiotherapy ( p = 0.035; R = 0.196). The auditory complaint analysis shows that most of the subjects had tinnitus and speech understanding difficulty, even with a normal auditory threshold. CONCLUSIONS: Cancer treatment causes hearing loss, associated with the administration of chemotherapy and radiotherapy. Cyclophosphamide increased the risk of causing hearing loss. Complaints of tinnitus and speech understanding difficulty were observed.

RESUMO INTRODUÇÃO: O tratamento quimioterápico e radioterápico na oncologia tem repercussão na saúde auditiva e pode lesar estruturas da orelha interna. Ocasiona perda auditiva, geralmente bilateral e irreversível. OBJETIVO: Identificar casos de perda auditiva sensorioneural e sua relação com a média de sessões de quimioterapia e radioterapia, com queixas de zumbido e dificuldade de entendimento da fala, bem como sua relação com medicamentos quimioterápicos. MÉTODO: Estudo de coorte histórica com corte transversal, clínico, observacional, analítico e retrospectivo em 58 sujeitos de um hospital público de Sergipe diagnosticados com neoplasia. Realizou-se anamnese, avaliação audiológica tonal convencional e pesquisa do limiar de reconhecimento de fala. RESULTADOS: Das 116 orelhas; 25,9% apresentaram perda auditiva sensorioneural caracterizada por alterações nas frequências agudas. Observou-se correlação significativa entre perda auditiva e associação da quimioterapia e radioterapia (p = 0,035; R = 0,196). Na análise das queixas auditivas, verificou-se que a maioria apresentou zumbido e dificuldade de entendimento de fala, mesmo com limiares auditivos normais. CONCLUSÕES: O tratamento oncológico gera perda auditiva, que foi determinada pela associação da quimioterapia e radioterapia. Ciclofosfamida aumentou as chances de gerar perda auditiva. Verificou-se presença de queixas de zumbido e dificuldade de entendimento da fala.

Effects of the reduction of caffeine consumption on tinnitus perception / Efeitos da redução no consumo de cafeína sobre a percepção do zumbido

INTRODUCTION: For many years, excessive caffeine consumption has been touted as an aggravating factor for tinnitus. The pathophysiology behind this effect is probably related to the blockage of adenosine receptors by the action of caffeine on the central nervous system. OBJECTIVE: To evaluate the effects of reduction of coffee consumption on tinnitus sensation and to identify subgroups more prone to benefit from this therapeutic strategy. Study design: prospective. METHODS: Twenty-six tinnitus patients who consumed at least 150 mL of coffee per day were selected. All were asked to reduce their coffee consumption. The Tinnitus Handicap Inventory (THI) questionnaire was completed by the patients before and after the reduction of coffee consumption, as well as a visual-analogue scale (VAS) graduated from 1 to 10. RESULTS: THI and VAS scores were significantly reduced (p < 0.05). In the subgroups less than 60 years old, bilateral tinnitus and daily coffee consumption between 150 and 300 mL showed a significantly greater reduction of THI and VAS scores. CONCLUSION: Patients under 60 years of age with bilateral tinnitus and daily coffee consumption between 150 and 300 mL are more prone to benefit from consumption reduction. Thirty-day observation periods may be helpful for a better therapeutical decision. .

INTRODUÇÃO: O consumo abusivo de cafeína vem sendo descrito como fator de piora e causa do zumbido há muitos anos. A fisiopatologia deste efeito está provavelmente relacionada ao bloqueio dos receptores inibitórios adenosínicos pela cafeína no sistema nervoso central. OBJETIVO: Avaliar os efeitos da redução do consumo de cafeína na percepção do zumbido e identificar subgrupos de pacientes mais propensos a benefícios com esta proposta. Tipo de estudo: prospectivo. MÉTODO: Selecionados 26 pacientes com zumbido neurossensorial e consumo diário superior a 150 mL de café. Os efeitos da redução do consumo foram avaliados através do Tinnitus Handicap Inventory (THI) e da escala visual-análoga (EVA). RESULTADOS: Houve redução estatisticamente significativa (p < 0,05) nos escores do THI e EVA. Nos subgrupos com idade inferior a 60 anos, zumbido bilateral e consumo diário de café entre 150 e 300 mL apresentaram maior redução dos escores THI e EVA. CONCLUSÃO: Em pacientes com idade inferior a 60 anos, zumbido bilateral e consumo diário de café entre 150 e 300 mL apresentaram benefícios com a redução no consumo diário de cafeína. Períodos observacionais de 30 dias podem ser úteis para a decisão terapêutica. .

First report onoototoxicity of meglumine antimoniate / Primeiro relato de ototoxicidade pelo antimoniato de meglumina

Introduction: Pentavalent antimonials are the first drug of choice in the treatment of tegumentary leishmaniasis. Data on ototoxicity related with such drugs is scarcely available in literature, leading us to develop a study on cochleovestibular functions. Case Report: A case of a tegumentary leishmaniasis patient, a 78-year-old man who presented a substantial increase in auditory threshold with tinnitus and severe rotatory dizziness during the treatment with meglumine antimoniate, is reported. These symptoms worsened in two weeks after treatment was interrupted. Conclusion: Dizziness and tinnitus had already been related to meglumine antimoniate. However, this is the first well documented case of cochlear-vestibular toxicity related to meglumine antimoniate.

Introdução: Antimoniais pentavalentes são os fármacos de primeira escolha no tratamento da leishmaniose tegumentar. Dados de ototoxicidade relacionados a tais fármacos são escassos na literatura, o que nos levou a desenvolver um estudo de funções cócleo-vestibulares. Relato de caso: Relatamos caso de paciente masculino de 78 anos com leishmaniose tegumentar, que apresentou aumento significativo dos limiares auditivos com zumbido e tontura rotatória grave durante o tratamento com antimoniato de meglumina. Os sintomas pioraram até duas semanas após a interrupção do tratamento. Conclusão: Tontura e zumbido já tinham sido associados ao antimoniato de meglumina. Entretanto, este é o primeiro caso bem documentado de toxicidade cócleo-vestibular relacionado ao antimoniato de meglumina.

Cisplatin-based chemotherapy: Add high-frequency audiometry in the regimen.

Background : Cisplatin-induced ototoxicity shows high interindividual variability and is often accompanied by transient or permanent tinnitus. It is not possible to identify the susceptible individuals before commencement of the treatment. We conducted a prospective, randomized and observational study in a tertiary care centre and evaluated the effects of different doses of cisplatin on hearing. Materials and Methods : Fifty-seven patients scheduled for cisplatin-based chemotherapy were included in the study. All patients were divided into three groups depending on the dose of cisplatin infused in 3 weeks. Results : The subjective hearing loss was found in seven patients, while six patients had tinnitus during the chemotherapy. The hearing loss was sensorineural, dose dependent, symmetrical, bilateral and irreversible. Higher frequencies were first to be affected in cisplatin chemotherapy. Conclusion : As use of high-frequency audiometry is still limited in research work only, we need a strict protocol of adding high-frequency audiometry in the cisplatin-based chemotherapy regimen.

Audiological findings in individuals exposed to organic solvents: case studies.

Millions of people around the world are exposed to industrial organic solvents such as toluene and xylene in the manufacturing sectors. Solvents are neurotoxic substances that are detrimental to the functioning of the nervous system, including the central auditory nervous system (CANS). This study investigated hearing and auditory processing in seven individuals with a history of exposure to industrial solvents. A battery of audiological tests was administered to all subjects: pure tone, speech, and impedance audiometry, otoacoustic emissions tests, auditory brainstem responses, middle latency responses, as well as the SCAN-A and R-SPIN tests with low predictability sentence lists. All individuals in this study exhibited findings consistent with retrocochlear and/or central abnormality. Two of the seven subjects in this study had normal pure tone thresholds at all frequencies bilaterally, yet showed abnormal retrocochlear/central results on one or more tests. The auditory test battery approach used in this study appears to be valuable in evaluating the pathological conditions of the CANS in solvent-exposed individuals.

Manifestações otoneurológicas associadas à terapia anti-retroviral / Otoneurological manifestations associated with antiretroviral therapy

Ototoxicidade e terapia anti-retroviral parecem estar associadas. O objetivo desse estudo foi avaliar essa possível correlação. Foram avaliados 779 prontuários médicos de pacientes infectados pelo HIV e regularmente acompanhados, sendo 162 tratados com terapia anti-retroviral e 122 não tratados (controle). Pacientes em tratamento eram mais velhos (média 42 anos), com maior tempo de confirmação sorológica (80 meses) e com menor carga viral (p=0,00). CD4+ foi semelhante entre os grupos (P=0,60). No grupo tratado, três (1,8 por cento) casos de perda auditiva idiopática e dois (1,3 por cento) de perda auditiva relacionada a otosclerose foram observadas e ambas iniciadas após terapia anti-retroviral. Nenhuma diferença estatística relacionada à perda auditiva idiopática foi encontrada entre os grupos. Enquanto estudos descritivos consideram possível ototoxidade associada à terapia anti-retroviral, esse possível efeito adverso não foi relacionado à terapia anti-retroviral neste estudo. Contrariamente, otosclerose poderia estar correlacionada à terapia anti-retroviral. Este assunto merece ser estudado.

Ototoxicity and antiretroviral therapy seem to be associated. The aim of this study was to evaluate this possible correlation. Evaluations were carried out on 779 medical records from HIV-infected patients who were being regularly followed up, of whom 162 were being treated with antiretroviral therapy and 122 were untreated (controls). The patients undergoing treatment were older (mean: 42 years), had had serological confirmation for longer times (80 months) and had smaller viral loads (P = 0.00). CD4+ was similar between the groups (P = 0.60). In the treated group, three cases (1.8 percent) of idiopathic hearing loss and two (1.3 percent) of otosclerosis-related hearing loss were observed, which both started after antiretroviral therapy. No statistical difference relating to idiopathic hearing loss was found between the groups. While descriptive studies consider possible ototoxicity associated with antiretroviral therapy, this possible adverse effect was not related to the antiretroviral therapy in this study. Conversely, otosclerosis might have been correlated with antiretroviral therapy. This issue deserves to be studied.

Ototoxidade da cisplatina: série de casos / Cisplatin ototoxicity: series of cases

OBJETIVO: Avaliar a evolução clínica e audiométrica de indivíduos submetidos à quimioterapia com cisplatina. MÉTODOS: Foram avaliadas descritivamente quatro voluntárias, todas do gênero feminino e com idades entre 38 e 69 anos. Todas realizaram exame otorrinolaringológico e avaliação audiológica com audiometria tonal, vocal e imitanciometria antes e após o tratamento com cisplatina. Além disso, todas foram avaliadas subjetivamente pré e pós-quimioterapia por meio de aplicação de questionário. RESULTADOS: Uma voluntária não apresentou alterações auditivas. Três voluntárias apresentaram déficit auditivo sensorioneural, bilateral, de leve a moderado nas freqüências de 6kHz e 8 kHz após quimioterapia com cisplatina. Todas as voluntárias que desenvolveram perda auditiva apresentaram a queixa de zumbido após o tratamento. CONCLUSÃO: Por ser a cisplatina considerada droga ototóxica, é necessário o acompanhamento audiológico de pacientes submetidos à quimioterapia com essa droga, no intuito de realizar o diagnóstico precoce de perdas auditivas.

OBJECTIVE: To evaluate the clinic and audiometric evolution of individuals who underwent chemotherapy with cisplatin. METHODS: Four volunteers, all women, between 38 and 69 years of age were descriptively evaluated. All did otorino-laryngoiatric exam and audiometric evaluation with tonal and speech audiometric and impedance tests before and after treatment with cisplatin. In addition, all were subjectively evaluated pre- and post-chemotherapy by a questionnaire. RESULTS: One volunteer did not present auditory disorders. Three volunteers presented bilateral hearing loss, mild to moderate in 6kHz and 8kHz frequencies, after chemotherapy with cisplatin. All volunteers who developed hearing loss after treatment also presented tinnitus. CONCLUSION: Since cisplatin is considered ototoxic, all individuals undergoing chemotherapy with this drug must be submitted to audiometric monitoring for early diagnosis of a hearing loss.

Avaliações audiométrica e vestibular em mulheres que utilizam o método contraceptivo hormonal oral / Audiometric and vestibular evaluation in women using the hormonal contraceptive method

OBJETIVO: Correlacionar o uso de contraceptivo hormonal oral com possíveis alterações auditivas e vestibulares. MÉTODOS: Aplicou-se anamnese, teste audiométrico e teste vestibular em 60 mulheres entre 14 e 35 anos, sendo que 30 mulheres faziam uso do método contraceptivo hormonal oral composto por estrógeno e progesterona (grupo de risco), por um período igual ou superior a 6 meses, sem queixas auditivas e vestibulares anteriores ao uso do mesmo; e 30 mulheres que nunca fizeram uso desses hormônios (grupo controle), sem queixas auditivas e vestibulares. A anamnese foi utilizada como critério de seleção da amostra. RESULTADOS: Com base nos achados otoneurológicos através de uma pesquisa quantitativa, pode-se verificar uma prevalência da Síndrome Vestibular Periférica Irritativa e de zumbidos no grupo de risco, sem alterações audiométricas. CONCLUSÃO: O uso do método contraceptivo hormonal oral pode ocasionar alterações funcionais na orelha interna, principalmente zumbido e Síndrome Vestibular Periférica Irritativa no grupo de risco, mas não evidenciou alterações de limiares auditivos.

AIM: To co-relate the use of hormonal contraceptives with positive Auditory and Vestibular alterations. METHODS: medical history taking, audiometric test and vestibular test was applied to 60 women between the ages of 14 and 35 years old, and 30 of these women are on oral hormonal contraceptive consisting of Estrogen and Progesterone (risk group), for 6 months or more, that had no Auditory or Vestibular complaints prior to the usage of hormones; and 30 women that had never used these hormones (control group), with no Auditory or Vestibular complaints. Medical history was used to select the sample. RESULTS: Based on otoneurological findings, through quantitative research, we could see the prevailing Irritatative Peripheral Vestibular Syndrome and tinnitus in the risk group, without audiometric alterations. CONCLUSION: The use of oral contraceptives can provoke functional alterations in the inner ear, specially tinnitus and Irritative Peripheral Vestibular Syndrome in the risk group; but auditory threshold alterations were not evident.