Ascorbic acid reduces noise-induced nitric oxide production in the guinea pig ear

OBJECTIVES: Noise-induced hearing loss can be caused, among other causes, by increased nitric oxide (NO) production in the inner ear leading to nitroactive stress and cell destruction. Some studies in the literature suggest that the degree of hearing loss (HL) could be reduced in an animal model through ascorbic acid supplementation. To identify the effect of ascorbic acid on tissue-dependent NO content in the inner ear of the guinea pig, we determined the local NO production in the organ of Corti and the lateral wall separately 6 hours after noise exposure. STUDY DESIGN: Prospective animal study in guinea pigs. METHODS: Over a period of 7 days, male guinea pigs were supplied with minimum (25 mg/kg body weight/day) and maximum (525 mg/kg body weight/day) ascorbic acid doses, and afterwards exposed to noise (90 dB sound pressure level for 1 hour). The acoustic-evoked potentials were recorded before and after noise exposure. The organ of Corti and the lateral wall were incubated differently for 6 hours in culture medium, and the degree of NO production was determined by chemiluminescence. RESULTS: Ascorbic acid treatment reduced the hearing threshold shift after noise exposure depending on concentration. When the maximum ascorbic acid dose was substituted, NO production was significantly reduced in the lateral wall after noise exposure and slightly reduced in the organ of Corti. CONCLUSIONS: Oral supplementation of the natural radical scavenger ascorbic acid reduces the NO-production rate in the inner ear in noisy conditions. This finding supports the concept of inner ear protection by ascorbic acid supplementation.     

NOS在分泌性中耳炎所致感音神经性聋中的作用

目的:探讨NOS及NO在分泌性中耳炎(SOM)所致感音神经性聋(SNHL)中的作用。方法:治疗前分别抽取16例伴有SNHL的SOM患者(A组)及16例不伴有SNHL的SOM患者(B组)的中耳积液,检测两组中耳积液内NOS活性和NO含量。结果:A组中耳积液内NO含量(181.19±44.31)μmol/L明显高于B组(137.00±40.67)μmol/L(P<0.01),A组中耳积液内NOS活性(97.69±29.62)U也明显高于B组(75.50±26.99)U(P<0.05)。结论:NO可能通过直接损伤和与其他炎症递质共同作用增强局部炎症反应,在SOM所致的SNHL过程中发挥重要作用。     

一氧化氮合酶抑制剂和神经营养因子3对噪声暴露下豚鼠耳蜗的保护作用

目的观察一氧化氮合酶抑制剂——N-硝基左旋精氨酸甲酯（N^G-nitro-L-arginine methyl ester，L-NAME）和神经营养因子3（neurotrophin 3，NT3）对噪声性听力损失的保护作用。方法80只雄性杂色豚鼠按区组随机分为非噪声组（n=20）和噪声暴露组（n=60），噪声暴露组又分为生理盐水组（n=20）、L-NAME组（n=20）、L-NAME＋NT3组（n=20）。L-NAME组和L-NAME＋NT3组动物在噪声暴露（4kHz倍频程、声压级115dB，5h）之前2d和噪声暴露前30min给予L-NAME 10mg／kg（腹腔注射），生理盐水组动物给予等体积的生理盐水。NT3（10μg／ml）在噪声暴露前4d经微量渗透泵（200μl，0．5μl／h）输入到L-NAME＋NT3组动物的右侧耳蜗鼓阶，持续到噪声暴露后10d。噪声暴露前和暴露后10d测试听性脑干反应（auditory brainstem response，ABR），暴露后3d测试耳蜗组织一氧化氮（nitric oxide，NO）水平，最后一次ABR测试后计数耳蜗毛细胞的存活率。结果无噪声暴露组动物无明显的听力改变和毛细胞缺失；生理盐水组动物的ABR阈移、毛细胞缺失率及耳蜗组织NO水平均高于L-NAME组和L-NAME＋NT3组，差异有统计学意义（P值均〈0．01）；与L-NAME组相比，L-NAME＋NT3组豚鼠的ABR阈移减小，差异有统计学意义（P〈0．01），而耳蜗组织NO水平和毛细胞缺失率差异则没有统计学意义（P=0．197及P=0．095）。结论与单独给予L-NAME相比，联合使用NT3可以更大程度减轻噪声对豚鼠耳蜗的损伤。     

一氧化氮在豚鼠耳蜗作用的实验研究

为探讨ＮＯ在内耳的作用，采用外淋巴给药途径，观察一氧化氮气体（ＮＯ）、Ｌ－精氨酸、硝普钠及一氧化氮合酶（ＮＯＳ）拮抗剂Ｎ－甲基－Ｌ－精氨酸对耳蜗蜗内电位（ＥＰ）、复合动作电位（ＣＡＰ）及耳蜗微音器电位（ＣＭ）的影响。结果表明，Ｎ－甲基－Ｌ－精氨酸可以使ＥＰ减小５０％，ＣＡＰ振幅降低３３％及ＣＭ振幅略有降低，在此基础上，用Ｌ－精氨酸外淋巴灌流可以逆转Ｎ－甲基－Ｌ－精氨酸所致的改变。ＮＯ持续外淋巴缓释能使Ｎ－甲基－Ｌ－精氨酸导致的ＥＰ、ＣＡＰ及ＣＭ的改变恢复，并超过正常，随之出现快速下降。外淋巴灌流硝普钠后，ＥＰ、ＣＡＰ及ＣＭ短暂升高后逐渐下降，并维持在较低水平。ＣＡＰＮ１波及ＣＭ潜伏期的变化规律与其振幅的变化规律基本一致。结果提示，ＮＯ在生理条件下维持内耳功能，可能参与耳蜗毛细胞微机械特性及敏感性的调节，过量表达可以产生耳蜗毒性     

Development of cis-platinum-induced hearing loss in guinea pigs

Summary The resultant hearing loss can be variable if cis-dichlorodiammineplatinum is given to guinea pigs. In order to find out more about these differences, we used brainstem audiometry to study the start and development of hearing loss over time for several frequencies. Our results confirmed previous observations that hearing loss starts at the higher frequencies but can also occur at lower frequencies. Furthermore, there were great differences in the start and the rate of the increase of hearing loss found in the individual animals. The individual differences in susceptibility can not be explained by one factor alone, but by the combination of three factors, namely deviation point, slope and length of survival.This study was supported by the Heinsius Houbolt Foundation     

Rapid Elevation of Gentamicin Levels in the Human Labyrinth Following Intravenous Administration

Hypothesis Adequate quantities of labyrinthine fluid can be sampled from the human labyrinth to perform quantitative analysis of medications. A rapid elevation of intralabyrinthine gentamicin levels after intravenous administration can be measured. A model for the sampling of human inner ear fluid in this manner is described. Background The risk of aminoglycoside ototoxicity has been a long‐standing concern. The kinetics of gentamicin diffusion into the inner ear have been extrapolated to humans from various animal models. The validity of extrapolation to humans is unknown. We have developed a new model to measure the uptake of gentamicin in vivo. Methods A single intravenous dose of gentamicin (80 mg) was given perioperatively to 13 patients undergoing translabyrinthine acoustic neuroma surgery. The lateral semicircular canal and vestibule were opened and a microsyringe was used to obtain a sample of labyrinthine fluid concomitant with a serum sample. The gentamicin concentration of the labyrinthine fluid and serum was analyzed using a standard chemistry analyzer. Results After parenteral administration of gentamicin, fluid was obtained from the inner ear of 13 acoustic neuroma patients. Inner ear concentrations were between 1.0 and 3.8 mg/L. Serum gentamicin levels ranged from 1.2 to 10.5 mg/L. Conclusions This method allows the sampling of intralabyrinthine fluid in humans. Gentamicin was noted immediately in the labyrinth after intravenous administration. This model may be expanded to measure other compounds given either by intravenous or transtympanic routes.     

Noise-induced hearing loss in rats with renal hypertension

Genetically hypertensive rats have been found in previous studies to be more susceptible than normotensive rats to the formation of lesions of the inner ear as a result of excess noise. The present study was designed to investigate whether or not that susceptibility is a direct result of the high blood pressure. Hypertension was induced in 28 Sprague-Dawley rats by placing a 0.25 mm wide silver clip on one renal artery. Systolic blood pressure was measured indirectly by a tail-cuff technique 3 weeks after the operation and again after noise exposure. The animals were kept for one month in noise conditions (100 dB L_eq (lin)) simulating those in an industrial milieu. The frequency range was adjusted to correlate to the hearing range of the rat. Auditory sensitivity was assessed electrophysiologically by recording auditory brain stem responses to pulses of $\text{1}\text{3}\text{-octave}$ filtered full-cycle sine waves. The results showed no correlation between hearing loss and systolic blood pressure. There was no difference between the audiograms obtained from rats with a systolic pressure below 160 mmHg and those obtained from rats with systolic pressures of between 170 and 255 mmHg. These results do not support the hypothesis that high blood pressure is a mechanism underlying noise-induced hearing loss.     

Nitric oxide synthase inhibitor reduces noise-induced cochlear damage in guinea pigs

Conclusion. The results obtained in this study indicate that N^G-nitro-L-arginine methyl ester (L-NAME) protects cochlear damage from acoustic trauma through reducing the production of nitric oxide (NO). Objectives. This study aimed to explore whether NO synthase inhibitor L-NAME could reduce cochlear damage in acoustic trauma. Materials and methods. Seventy guinea pigs (300–350g) were divided randomly into four groups (n=20 in groups I, III, and IV; n=10 in group II). Two days consecutively and 30min before noise exposure (4kHz octave band, 115dB SPL 5h), subjects received an injection of 5ml saline/kg (groups I and III) or 10mg/kg L-NAME (groups II and IV). Sham-exposed guinea pigs were listed as groups I and II. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold and histologically by survival of outer hair cells (OHCs). NO level of cochlear tissue was assayed 3days after noise exposure. Results. Group III showed significantly greater OHC loss, threshold shifts and NO level compared with group I and group IV. Compared with group III, noise-induced elevation in NO level in the cochlea was significantly attenuated by L-NAME (p<0.001).     

Dexamethasone base conserves hearing from electrode trauma-induced hearing loss

Objective/Hypothesis: Local treatment of the cochlea after electrode insertion trauma with dexamethasone base conserves hearing against trauma‐induced loss. Study Design: Laboratory animal study. Methods: A guinea pig model of electron insertion trauma (EIT)‐induced hearing loss (HL) used 44 guinea pigs sub‐divided into four groups: 1) unoperated, controls (Controls, n = 44); 2) EIT, untreated (EIT, n = 15); 3) EIT plus artificial perilymph (EIT + AP, n = 15); and 4) EIT plus dexamethasone base (EIT + DXMb, n = 14). Cochleae that received EIT were randomly selected with contralateral, unoperated cochleae as internal controls. Auditory brainstem responses (ABRs) in response to 0.5 to 16 kHz pure tones were obtained before surgery, immediately after surgery (0 day), and on post‐EIT days 3, 7, 14, and 30. Hair cell counts were obtained from stained organ of Corti specimens from all four groups (n = 3/group). Data were analyzed using analysis of variance and a Tukey‐Kramer honestly significant difference post hoc test with significance alpha set at <0.05 (hearing) and <0.001 (hair cells). Results: There were significant differences (<0.05) between the ABR thresholds of unoperated (control) and contralateral operated (experimental) ears of EIT and of EIT + AP groups for all tested frequencies. There was no statistical difference (>0.05) in ABR thresholds in the EIT + DXMb versus control groups for 0.5 to 4 kHz tones. DXMb treatment protected hair cells from EIT‐induced damage and loss while AP treatment did not. Conclusion: The absence of significant differences in hearing thresholds between the EIT + DXMb group and control ears in response to 0.5 to 4 kHz tones demonstrates that DXMb is as effective as the aqueous form of dexamethasone in conserving hearing against EIT‐induced loss.     

白噪声对豚鼠耳蜗核一氧化氮合酶活性的影响

采用硫辛酰胺脱氢酶组织化学方法及图象分析技术，研究白噪声暴露后豚鼠耳蜗核一氧化氮合酶（ＮＯＳ）神经元及ＮＯＳ活性的变化与听阈的关系，探讨豚鼠耳蜗核ＮＯＳ神经元在白噪声损伤过程中可能的作用。结果表明，白噪声暴露后耳蜗核ＮＯＳ阳性神经元的数量及染色强度明显增加，２周达到高峰，３￣４周持续高表达，至５周有所恢复，仍高于正常水平。白噪声暴露后７ｄ以内，耳蜗核ＮＯＳ活性与ＡＢＲ阈值有分离现象，７ｄ后，ＮＯＳ     

Low-dose,long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat

Conclusion. Physiological and morphological assessments indicated that low-dose and long-term caroverine delivery might be a new approach to protect against impulse noise-induced hearing loss. Background. Although the exact mechanisms by which impulse noise causes hearing loss are still unclear, there is accumulating evidence that increased reactive oxygen species (ROS) production and excessive glutamate released from the inner hair cells lead to hair cell loss and consequently hearing loss. Caroverine is an antagonist of two glutamate receptors, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the inner ear, as well as an antioxidant. Materials and methods. In this study, caroverine was delivered subcutaneously using an osmotic pump. This kind of delivery has the advantage, via continuous, long-term and low dose drug administration, of avoiding systemic side effects. Results. It was shown that caroverine could significantly protect the cochlea against impulse noise trauma.     

感音神经性聋患儿中先天性内耳畸形的构成、影像学及临床听力学特征

目的:分析婴幼儿、儿童先天性感音神经性聋(SNHL)中先天性内耳畸形的构成、影像学及临床听力学特征。方法:回顾性分析2005-02-2010-01上海交通大学医学院附属上海儿童医学中心耳鼻咽喉科诊治的860例先天性SNHL患儿中,经颞骨高分辨率CT及MRI发现有先天性内耳畸形的125例(225耳)患儿的听力学及影像学资料。结果:860例先天性SNHL患儿中有先天性内耳畸形者占14.5%;累及双侧98例(78.4%),单侧27例(21.6%)。225耳中167耳(74.2%)为极重度聋,36耳(16%)为重度聋,22耳(9.8%)为中度聋。该组内耳畸形中,前庭水管扩大最多见(75.6%),其次为前庭畸形(32%),再次为耳蜗前庭畸形(23.1%)。耳蜗前庭畸形中以Mondini畸形最常见(55.8%),其次为共同腔畸形(28.9%)。累及耳蜗的内耳畸形中极重度聋者明显多于未累及耳蜗的内耳畸形中极重度聋者。结论:对了解中国婴幼儿、儿童先天性SNHL中先天性内耳畸形的构成,对先天性SNHL的病因诊断以及对包括助听器、耳蜗植入等在内的干预策略的制订及其预后有一定意义。     

噪声对豚鼠耳蜗核一氧化氮合酶阳性神经元及其基因表达的影响

为探讨豚鼠耳蜗核一氧化氮合酶（ｎｉｔｒｉｃｏｘｉｄｅｓｙｎｔｈａｓｅ，ＮＯＳ）神经元在白噪声损伤过程中可能的作用，采用硫辛酰胺脱氢酶（ＮＡＤＰＨ－ｄ）组织化学方法及半定量多聚酶链反应（ＰＣＲ）技术，研究白噪声暴露后豚鼠耳蜗核ＮＯＳ神经元及ＮＯＳｍＲＮＡ含量的变化以及与听阈的关系。结果表明，噪声暴露后耳蜗核ＮＯＳ阳性神经元的数量及染色强度明显增加，２周达高峰，３～４周持续高表达，５周有所恢复，但仍高于正常水平。耳蜗核ＮＯＳｍＲＮＡ含量的变化规律与形态学观察结果一致，２周组ＮＯＳｍＲＮＡ含量最高，是正常的５．０２倍。噪声暴露后ＡＢＲ阈移与耳蜗核ＮＯＳｍＲＮＡ含量呈正相关（ｒ＝０．９６５５，Ｐ＜０．０１）。提示耳蜗核ＮＯＳ阳性神经元可能参与了耳蜗神经损伤修复的调节，ＮＯＳ基因的高表达是噪声性聋发病机制中不可忽视的重要因素之一。     

Clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss

OBJECTIVES/HYPOTHESIS: The role of antiendothelial cell antibodies in systemic vasculitis has been reported. The aim of the study was to define the clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss. STUDY DESIGN: A prospective study in patients with sudden sensorineural hearing loss. METHODS: Serum samples were taken from 59 consecutive patients with sudden sensorineural hearing loss at time of presentation and from 28 normal control subjects. Indirect immunofluorescence assay was used to detect antiendothelial cell antibodies. RESULTS: The prevalence of antiendothelial cell antibody detection was 54% (32 of 59 patients), with a statistically significant difference between patients and control subjects (P =.0004). Antiendothelial cell antibody positivity was significantly associated with absent recovery of hearing loss (P =.0020). CONCLUSIONS: The cytotoxicity to endothelial cells of the inner ear by antiendothelial cell antibody-positive sera might play a role in causing the stria vascularis damage in immune-mediated sudden sensorineural deafness. The appearance of antiendothelial cell antibody is related to the poor outcome of hearing loss, and its detection could be helpful in the selection of particular patients with sensorineural hearing loss for specific immunosuppressive treatments.     

Differences between acoustic trauma and other types of acute noise-induced hearing loss in terms of treatment and hearing prognosis

Abstract

Objectives: To evaluate the differences between acoustic trauma (AT) and other types of acute noise-induced hearing loss (ANIHL), we performed a literature search and case reviews.

Methods: The literature search based on online databases was completed in September 2016. Articles on ANIHL and steroid treatment for human subjects were reviewed. The source sounds and treatment sequelae of our accumulated cases were also reviewed. Hearing loss caused by gun-shots and explosions was categorized into the AT group, while hearing loss caused by concerts and other noises was categorized into the ANIHL group.

Results: Systemic steroid treatment did not appear to be effective, at least in the AT group, based on both the literature and our case reviews. However, effective recovery after treatment including steroids was observed in the ANIHL group. The difference in hearing recovery between the AT and ANIHL groups was statistically significant (p?=?.030), although differences in age, days from the onset to treatment and pretreatment hearing levels were not significant.

Conclusions: Hearing recovery from AT is very poor, whereas, ANIHL is recoverable to some extent. Therefore, it is essential to differentiate between these two groups for accurate prediction of the hearing prognosis and evaluation of treatment effects.     

Improvement in inner ear blood flow by nitric oxide following experimentally induced cochlear thrombosis in anesthetized guinea pigs

The nitric oxide (NO) donor sodium nitroprusside (SNP) applied to the round window membrane has recently been found to increase cochlear blood flow (CoBF) in normal guinea pigs and in normal and presbyacusic mice. This study examined the effect of topical applications of SNP on experimentally impaired CoBF in anesthetized guinea pigs. Small (3 μl) portions of 3% SNP were applied to the round window niche of both normal and thrombosed cochleas. Local vascular impairment was produced by ferromagnetic thrombosis of cochlear blood vessels and the microcirculation measured using laser Doppler flowmetry. Ferromagnetic thrombosis resulted in a mean decrease of CoBF to 52% of baseline. There was a clear improvement in mean CoBF to 84% of baseline by the topical application of SNP that depended on the degree of ischemic damage produced. Under neuroleptanalgesia and ketamine-xylazine anesthesia, significant increases in CoBF were measured in normal ears as well as in the thrombosed ones. However, several SNP applications were needed to improve the impaired CoBF, while a single portion was sufficient in the normal cochlea to cause a drastic increase in mean CoBF to 234% of baseline. In urethane-anesthetized animals, no flow increase was found despite repeated drug administration. Careful evaluation of the laser Doppler signals was necessary to accurately determine the concentrations of the moving blood cells and their mean velocities. Received: 8 August 1997 / Accepted: 11 February 1998     

Etiology of single-sided deafness and asymmetrical hearing loss

Abstract

Conclusions: The present study revealed that various etiologies are involved in single-sided deafness (SSD), and that the cause of SSD and asymmetrical hearing loss (AHL) differed greatly between congenital/early-onset cases and adult cases. Clarification of the etiology is the first step toward providing appropriate intervention.

Objectives: The study aimed to clarify the etiology of SSD and AHL patients.

Methods: The etiology of a total of 527 SSD or AHL patients who visited Shinshu University Hospital between 2006 and 2016 were analyzed by imaging as well as serological tests for mumps virus, and CMV DNA testing.

Results: In our cohort of congenital/early-onset SSD (n?=?210), the most prevalent cause in children was cochlear nerve deficiency (43.7%; 87 of 199 patients undergoing CT and/or MRI), followed by CMV infection, mumps infection, anomalies of the inner ear, ANSD, and other rare etiologies. In contrast, half of the adult SSD patients presented with idiopathic sensorineural hearing loss, followed by various types of otitis media, cerebellopontine angle tumor and other rare etiologies.     

内源性一氧化碳对变应性鼻炎豚鼠诱导型一氧化氮合酶表达的影响

目的 制备豚鼠变应性鼻炎(allergic rhinitis,AR)动物模型,研究在AR豚鼠模型中内源性一氧化碳(carbon monoxide,CO)对诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达的影响.方法 24只豚鼠以随机数字表法分为4组,每组6只.第1组以生理盐水处理作为正常对照组,第2(AR组)、3、4组以卵清蛋白(ovalbumin,OVA)致敏,制成AR动物模型,第3、4组再分别以血红素氧合酶1(hemeoxygenase 1,HO-1)诱导剂氯化血红素和抑制剂锌原卟啉干预处理,分别作为HO诱导组和HO抑制组,分别测定各组豚鼠血浆中碳氧血红蛋白(carboxyhemoglobin,COHb)的百分含量(用来代表血浆中CO含量),并采用实时荧光定量反转录聚合酶链反应(RT-PCR)法测定鼻黏膜中HO-1和iNOS的相对表达量.结果 第2、3、4组豚鼠AR造模成功.血浆COHb含量(x-±s,以下同)第2组(2.27%±1.13%)高于第1组(1.08%±0.24%),差异有统计学意义(q=4.10,P＜0.01);第3组(3.17%±0.68%)高于第2组,差异有统计学意义(q=3.12,P＜0.05).鼻黏膜中HO-1、iNOS的相对表达量(x-±s,以下同)第2组[分别为(7.80±1.60)×10~(-3)和(5.81±0.05)×10~(-3)]高于第1组[分别为(1.96±0.71)×10~(-3)和(0.97±0.05)×10~(-3)],差异有统计学意义(q值分别为5.52、7.21,P值均＜0.01),第3组[分别为(11.89±4.78)×10~(-3)和(7.42±0.70)×10~(-3)]高于第2组,差异有统计学意义(q值分别为3.86、2.22,P值均＜0.05),第4组[分别为(3.82±0.98)×10~(-3)和(2.34±0.04)×10~(-3)]低于第2组,差异有统计学意义(q值分别为3.76、5.18,P值均＜0.05).结论 内源性CO在AR中影响iNOS的表达.