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Abstract Objective: Previous studies have shown that hearing function is also vulnerable to the effects of diabetes mellitus which can be shown by brainstem auditory evoked potential and distortion product otoacoustic emission recordings. This study aimed to investigate the changes of brainstem auditory evoked potential and distortion product otoacoustic emission in hyperglycemia and whether there is a relationship between reactive oxygen substances production and hearing deterioration in the rat model. Methods: 25 streptozotocin induced diabetic rats were divided into three groups: control, high blood glucose, and diabetes mellitus. Brainstem auditory evoked potential and distortion product otoacoustic emission were recorded, and thiobarbituric acid reactive substances levels were measured in the brainstem tissue. Results: At 8 kHz, the latencies of I, II, III, IV, and V brainstem auditory evoked potential waves in high blood glucose and diabetes mellitus groups were elongated, at 16 kHz, only these wave latencies of the diabetes mellitus group were prolonged compared with the control group. A significant decrease was also found in distortion product otoacoustic emission amplitudes at 4, 6, 8, and 10 kHz in the high blood glucose and diabetes mellitus groups compared to the control group. There was a significant increase in thiobarbituric acid reactive substances values due to the increase in blood glucose levels in the high blood glucose and diabetes mellitus groups compared to the control group. Conclusion: These results suggested that high blood glucose levels may cause hearing impairment not only in the diabetic state but also in the period of hyperglycemia before the onset of manifest diabetes mellitus and reactive oxygen substances may play an important role in the pathophysiology of diabetes mellitus. We suggest that regulating high glucose levels even before the onset of manifest diabetes mellitus may prevent hazardous effects on hearing function. Level of evidence: Level 3.

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OBJECTIVE: Previous studies have shown that hearing function is also vulnerable to the effects of diabetes mellitus which can be shown by brainstem auditory evoked potential and distortion product otoacoustic emission recordings. This study aimed to investigate the changes of brainstem auditory evoked potential and distortion product otoacoustic emission in hyperglycemia and whether there is a relationship between reactive oxygen substances production and hearing deterioration in the rat model. METHODS: 25 streptozotocin induced diabetic rats were divided into three groups: control, high blood glucose, and diabetes mellitus. Brainstem auditory evoked potential and distortion product otoacoustic emission were recorded, and thiobarbituric acid reactive substances levels were measured in the brainstem tissue. RESULTS: At 8 kHz, the latencies of I, II, III, IV, and V brainstem auditory evoked potential waves in high blood glucose and diabetes mellitus groups were elongated, at 16 kHz, only these wave latencies of the diabetes mellitus group were prolonged compared with the control group. A significant decrease was also found in distortion product otoacoustic emission amplitudes at 4, 6, 8, and 10 kHz in the high blood glucose and diabetes mellitus groups compared to the control group. There was a significant increase in thiobarbituric acid reactive substances values due to the increase in blood glucose levels in the high blood glucose and diabetes mellitus groups compared to the control group. CONCLUSION: These results suggested that high blood glucose levels may cause hearing impairment not only in the diabetic state but also in the period of hyperglycemia before the onset of manifest diabetes mellitus and reactive oxygen substances may play an important role in the pathophysiology of diabetes mellitus. We suggest that regulating high glucose levels even before the onset of manifest diabetes mellitus may prevent hazardous effects on hearing function. LEVEL OF EVIDENCE: Level 3.

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Cisplatin is an antineoplastic agent widely used, and no effective treatments capable of preventing cisplatin-induced ototoxicity and neurotoxicity in humans have yet been identified. This study evaluated the effect of the anti-inflammatory annexin A1 (AnxA1)-derived peptide Ac2-26 in a cisplatin-induced ototoxicity model. Wistar rats received intraperitoneal injections of cisplatin (10 mg/kg/day) for 3 days to induce hearing loss, and Ac2-26 (1 mg/kg) was administered 15 min before cisplatin administration. Control animals received an equal volume of saline. Hearing thresholds were measured by distortion product otoacoustic emissions (DPOAE) before and after treatments. Pharmacological treatment with Ac2-26 protected against cisplatin-induced hearing loss, as evidenced by DPOAE results showing similar signal-noise ratios between the control and Ac2-26-treated groups. These otoprotective effects of Ac2-26 were associated with an increased number of ganglion neurons compared with the untreated cisplatin group. Additionally, Ac2-26 treatment produced reduced immunoreactivity on cleaved caspase 3 and phosphorylated ERK levels in the ganglion neurons, compared to the untreated group, supporting the neuroprotective effects of the Ac2-26. Our results suggest that Ac2-26 has a substantial otoprotective effect in this cisplatin-induced ototoxicity model mediated by neuroprotection and the regulation of the ERK pathway.

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BACKGROUND: Although several candidate-gene association studies have been conducted to investigate noise-induced hearing loss (NIHL) in humans, most are underpowered, unreplicated, and account for only a fraction of the genetic risk. Mouse genome-wide association studies (GWASs) have revolutionized the field of genetics and have led to the discovery of hundreds of genes involved in complex traits. The hybrid mouse diversity panel (HMDP) is a collection of classic inbred and recombinant inbred strains whose genomes have been either genotyped at high resolution or sequenced. To further investigate the genetics of NIHL, we report the first GWAS based on distortion product otoacoustic emission (DPOAE) measurements and the HMDP. METHODS: A total of 102 strains (n = 635) from the HMDP were evaluated based on DPOAE suprathreshold amplitudes before and after noise exposure. DPOAE amplitude variation was set at 60 and 70 dB SPL of the primary tones for each frequency separately (8, 11.3, 16, 22.6, and 32 kHz). These values provided an indirect assessment of outer hair cell integrity. Six-week-old mice were exposed for 2 h to 10 kHz octave-band noise at 108 dB SPL. To perform local expression quantitative trait locus (eQTL) analysis, gene expression microarray profiles were generated using cochlear RNA from 64 hybrid mouse strains (n = 3 arrays per strain). RESULTS: Several new loci were identified and positional candidate-genes associated with NIHL were prioritized, especially after noise exposure (1 locus at baseline and 5 loci after exposure). A total of 35 candidate genes in these 6 loci were identified with at least 1 probe whose expression was regulated by a significant cis-eQTL in the cochlea. After careful analysis of the candidate genes based on cochlear gene expression, 2 candidate genes were prioritized: Eya1 (baseline) and Efr3a (post-exposure). DISCUSSION AND CONCLUSION: For the first time, an association analysis with correction for population structure was used to map several loci for hearing traits in inbred strains of mice based on DPOAE suprathreshold amplitudes before and after noise exposure. Our results identified a number of novel loci and candidate genes for susceptibility to NIHL, especially the Eya1 and Efr3a genes. Our findings validate the power of the HMDP for detecting NIHL susceptibility genes.

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The mixture of ketamine and xylazine is widely used for the auditory brainstem response (ABR) measurement. Esketamine is twice as potent as ketamine. Our objective was to assess the influence of esketamine in mice undergoing cochlear function measurement including ABR and distortion product otoacoustic emission (DPOAE) measurement. C57Bl/6J mice were treated with an equivalent dose of analgesia and received either a single intraperitoneal (ip) injection of 100 mg/kg ketamine and 25 mg/kg xylazine or 50 mg/kg esketamine and 25 mg/kg xylazine. Hearing thresholds, peak latencies of waves I and V, and DPOAE thresholds were recorded. Time to loss of righting and time to regain righting were also assessed. We found that hearing thresholds, the peak latencies of waves I and V, and DPOAE thresholds were similar between the two groups (all P>0.05). Time to regain righting was significantly shorter in the esketamine group (P<0.001) than in the ketamine group. We concluded that when using equivalent doses of analgesia, esketamine may be an ideal substitute for ketamine during cochlear function test.

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Abstract Introduction: Previous research has suggested that individuals with different blood groups show varied incidences of noise-induced hearing loss. The reduced otoacoustic emissions amplitudes indicate the higher possibilities of outer hair cell damage for noise exposure. Objective: The objective is to analyze the characteristics of otoacoustic emissions, including the occurrence of spontaneous otoacoustic emission and the amplitudes of distortion product otoacoustic emission at certain frequencies in full term neonates with different ABO blood groups. Methods: A total of 80 selected full-term female neonates who passed the initial newborn hearing screen were enrolled into the study, with equal number of participants in four ABO blood groups (Blood Group A, Blood Group B, Blood Group AB, Blood Group O). Measurements of spontaneous otoacoustic emission and distortion product otoacoustic emission were performed in both ears for all participants. Results: (1) The blood group O participants showed significantly fewer spontaneous otoacoustic emission occurrences than the other three blood groups (A = 70%, B = 80%, AB = 67%, O = 25%, p < 0.05). (2) The blood group O participants showed lower DPOAE amplitudes at 1257 Hz (M = 4.55 dB, SD = 8.36), 1587 Hz (M = 11.60 dB, SD = 6.57), 3174 Hz (M = 7.25 dB, SD = 5.99), 5042 Hz (M = 13.60, SD = 6.70) than participants with the other three blood groups in left ears (p < 0.05). In right ears, the blood group O participants showed reduced amplitudes at 1257 Hz (M = 6.55 dB, SD = 8.36), 1587 Hz (M = 13.60 dB, SD = 6.57), 3174 Hz (M = 7.65 dB, SD = 6.43), 5042 Hz (M = 13.65 dB, SD = 6.50) than participants from non-O blood groups (p < 0.05). Conclusion: Female individuals with blood group O have lower otoacoustic emissions values than individuals with the other three blood groups. We need to further investigate the possible relationships between ABO blood group and cochlear function, including the potential influences of noise damage on cochlear outer hair cells.

Resumo Introdução: Pesquisas anteriores sugeriram que indivíduos de diferentes grupos sanguíneos apresentam incidências distintas de perda auditiva induzida por ruído. As amplitudes reduzidas das emissões otoacústicas indicaram maiores ou menores possibilidades de danos às células ciliadas por exposição a ruídos. Objetivo: Analisar as características das emissões otoacústicas, inclusive a ocorrência de emissões otoacústicas espontâneas e as amplitudes de emissões otoacústicas por produto de distorção em determinadas frequências em neonatos a termo de diferentes grupos sanguíneos do sistema ABO. Método: Foram incluídos 80 neonatos a termo selecionados na triagem auditiva neonatal inicial para participar do estudo, com número igual de participantes de grupos sanguíneos do sistema ABO (grupo sanguíneo A, grupo sanguíneo B, grupo sanguíneo AB e grupo sanguíneo O). As emissões otoacústicas espontâneas e emissões otoacústicas por produto de distorção foram medidas em ambas as orelhas de todos os participantes. Resultados: (1) Os participantes do grupo sanguíneo O apresentaram ocorrências de emissões otoacústicas espontâneas significantemente menores do que os dos outros três grupos sanguíneos (A = 70%, B = 80%, AB = 67%, O = 25%, p < 0,05). (2) Os participantes do grupo sanguíneo O apresentaram amplitudes de emissões otoacústicas por produto de distorção mais baixas a 1257 Hz (M = 4,55 dB, DP = 8,36), 1587 Hz (M = 11,60 dB, DP = 6,57), 3174 Hz (M = 7,25 dB, DP = 5,99), 5042 Hz (M = 13,0, DP = 6,70) do que os participantes dos outros três grupos sanguíneos nas orelhas esquerdas (p < 0,05). Nas orelhas direitas, os participantes do grupo sanguíneo O apresentaram amplitudes reduzidas em 1257 Hz (M = 6,55 dB, DP = 8,36), 1587 Hz (M = 13,60 dB, DP = 6,57), 3174 Hz (M = 7,65 dB, DP = 6,43), 5042 Hz (M = 13,65 dB, DP = 6,50) em comparação aos participantes de grupos sanguíneos não O (p < 0,05). Conclusão: Os indivíduos do sexo feminino do grupo sanguíneo O apresentaram valores menores de emissões otoacústicas do que os indivíduos dos outros três grupos sanguíneos. É necessário continuar a investigar as possíveis relações entre o grupo sanguíneo ABO e a função coclear, inclusive as possíveis influências do dano por ruídos às células ciliadas externas da cóclea.

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INTRODUCTION: Previous research has suggested that individuals with different blood groups show varied incidences of noise-induced hearing loss. The reduced otoacoustic emissions amplitudes indicate the higher possibilities of outer hair cell damage for noise exposure. OBJECTIVE: The objective is to analyze the characteristics of otoacoustic emissions, including the occurrence of spontaneous otoacoustic emission and the amplitudes of distortion product otoacoustic emission at certain frequencies in full term neonates with different ABO blood groups. METHODS: A total of 80 selected full-term female neonates who passed the initial newborn hearing screen were enrolled into the study, with equal number of participants in four ABO blood groups (Blood Group A, Blood Group B, Blood Group AB, Blood Group O). Measurements of spontaneous otoacoustic emission and distortion product otoacoustic emission were performed in both ears for all participants. RESULTS: (1) The blood group O participants showed significantly fewer spontaneous otoacoustic emission occurrences than the other three blood groups (A=70%, B=80%, AB=67%, O=25%, p< 0.05). (2) The blood group O participants showed lower DPOAE amplitudes at 1257 Hz (M = 4.55 dB, SD = 8.36), 1587 Hz (M = 11.60 dB, SD = 6.57), 3174 Hz (M = 7.25 dB, SD = 5.99), 5042 Hz (M = 13.60, SD = 6.70) than participants with the other three blood groups in left ears (p < 0.05). In right ears, the blood group O participants showed reduced amplitudes at 1257Hz (M=6.55dB, SD=8.36), 1587Hz (M=13.60dB, SD=6.57), 3174Hz (M=7.65dB, SD=6.43), 5042Hz (M=13.65dB, SD=6.50) than participants from non-O blood groups (p<0.05). CONCLUSION: Female individuals with blood group O have lower otoacoustic emissions values than individuals with the other three blood groups. We need to further investigate the possible relationships between ABO blood group and cochlear function, including the potential influences of noise damage on cochlear outer hair cells.

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Introducción: Las emisiones otoacústicas (EOA) son sonidos generados por las células ciliadas externas (CCE). Se ha visto que la generación y registro de las EOA evocadas depende de factores técnicos de evaluación como el nivel de intensidad de los tonos primarios, relación frecuencial entre los tonos, etc. Objetivos: Estudiar el efecto de la variación de la intensidad de los tonos primarios en la amplitud de la respuesta de las EOA producto de distorsión (pd) en individuos con audición normal. Material y método: Se evaluaron 35 individuos a los cuales se les midieron EOApd utilizando diferentes intensidades de tonos primarios: Intensidad baja (I1=50dBSPL e I2=50dBSPL), intensidad media (I1=55dBSPL e I2=65dBSPL) e intensidad alta (I1=70dBSPL e I2=70dBSPL). Resultados: Se observó que para tonos primarios a bajas intensidades (I1=50dBSPL e I2=50dBSPL) existe una disminución tanto en amplitud y presencia de las EOApd, mientras que para tonos primarios a intensidades mayores (I1=55dBSPL e I2=65dBSPL - I1=70dBSPL e I2=70dBSPL) se evidenció un aumento en amplitud y presencia de EOApd en los sujetos estudiados. Conclusión: Se evidencian diferencias estadísticamente significativas en la amplitud de las EOApd al variar la intensidad de los tonos primarios. Por lo cual se puede establecer que las intensidades medias-altas son las más adecuadas para la evaluación de EOApd en sujetos con audición normal.

Introduction: Otoacoustic emissions (OAE) are sounds produced by outer hair cells. The generation and recording of evoked OAE depends on technical factors such as level of intensity of primary tones, frequency relationship between the tones, etc. Aim: To study the effect of varying the intensity of primary tones in the amplitude of the response of Distortion Product OAE (DP) in individuals with normal hearing. Material and method: 35 individuals were measured using different intensities OAEdp primary tones: Low Intensity (I1= I2 =50dBSPL 50dBSPL e), Medium Intensity (11= I2 =65dBSPL 55dBSPL e) and High Intensity (I1 =70dBSPL and I2 =70dBSPL). Results: Using Low primary tones (I1 =I2 =50dBSPL 50dBSPL) there is a decrease in amplitude and presence of DPOAE, while for primary tones at higher intensities (I1 and I2 = = 55dBSPL 65dBSPL -11 =70dBSPL and I2 =70dBSPL) an increase in amplitude and presence of OAEdp in subjects with normal hearing was observed . Conclusion: There are statistically significant differences in OAEdp amplitude by varying the intensity of the primary tones. Therefore medium-high intensities are best suited for the evaluation of OAEdp in subjects with normal hearing.

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As emissões otoacústicas transientes evocadas e as emissões otoacústicas por produtos de distorção vêm assumindo importância significativa na identificação de alterações cocleares. OBJETIVO: Através da monitorização das emissões otoacústicas, registrar os limiares dos produtos de distorção em condições normais e na presença de modificações eletrofisiológicas nas células ciliadas externas cocleares de ovelhas após a indução de hiperinsulinemia aguda. MATERIAL E MÉTODO: Estudo experimental com sete ovelhas no grupo-controle e sete no grupo-estudo. Os níveis de insulina e glicose foram verificados simultaneamente ao registro das emissões otoacústicas por produtos de distorção de 10 em 10 minutos, até o tempo de 90 minutos. O grupo-controle recebeu soro fisiológico, e o grupo-estudo, injeção em bolo de 0,1 U/kg de insulina humana regular. RESULTADOS: Houve diminuição significante nos limiares dos produtos de distorção no grupo-estudo em relação ao grupo-controle nas freqüências acima de 1.500 Hz e após o tempo de 60 minutos (P < 0,001). CONCLUSÃO: O estudo permitiu estabelecer os limiares das emissões otoacústicas por produtos de distorção em ovelhas com constante reprodutibilidade, o que mostra que o método é adequado para uso em investigações audiológicas e otológicas. Ficou, ainda, plenamente identificado que o hiperinsulinismo agudo foi capaz de provocar relevantes modificações nestes limiares.

Transient evoked otoacoustic emissions and distortion product otoacoustic emissions have gained significant importance in the identification of cochlear alterations. AIM: To record distortion product thresholds through the monitoring of otoacoustic emissions in normal conditions and in the presence of electrophysiologic changes in cochlear outer hair cells in sheep after hyperinsulinemia induction. MATERIAL AND METHODS: Experimental study, with seven sheep in the control group and seven in the study group. Insulin and glucose concentrations were measured simultaneously for the recording of distortion product otoacoustic emission every 10 minutes, all the way to 90 minutes. The control group received saline solution, and the study group received a bolus injection of 0.1 U/kg of regular human insulin. RESULTS: There was a significant reduction in distortion product thresholds in the study group when compared to the control group at frequencies greater than 1,500Hz and after 60 minutes (P < 0.001). CONCLUSION: This study established distortion product otoacoustic emission thresholds in sheep with constant reproducibility, demonstrating that the method is adequate for use in audiology and otology investigations. Results also fully confirm that acute hyperinsulinemia may cause important changes in these thresholds.

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