An update on drug design strategies to prevent acquired sensorineural hearing loss

Introduction: Acute sensorineural hearing loss is a dramatic event for the patient. Different pathologies might result in acute sensorineural hearing loss, such as sudden hearing loss, exposure to medications/drugs or loud sound. Current therapeutic approaches include steroids and hyperbaric oxygen in addition to other methods. Research activities of the past have shed light on the molecular mechanisms involved in damage to hair cells, the synapses at the hair cell spiral ganglion junction and the stria vascularis. Molecular events and signaling pathways which underlie damage to these structures have been discovered.

Areas covered: This paper summarizes current research efforts involved in investigating the molecular mechanisms involved in acute sensorineural hearing loss.

Expert opinion: While progress has been made in unraveling basic mechanisms involved in acute sensorineural hearing loss, it is difficult to translate basic concepts to the clinic. There are often conflicting data in animal and human studies on the effect of a given intervention. There is also a lack of high quality clinical trials (double blind, placebo controlled and high powered). However, this author is confident that research efforts will pay out and that some of these efforts will translate into new therapeutic options for patients with acute hearing loss.     

迟发性显性遗传性感音神经性聋的听力和言语表现及其对策

目的：探讨2家系迟发性显性遗传性感音神经性聋的听力和言语情况。方法：对2家系进行耳聋遗传调查和系统的听力学调查。结果：2家系6例听阈检查示全频程听阈重度升高，听阈曲线呈缓降型，其中2例3耳仅低频听力残存。2家系耳聋发生年龄有逐代提前、代代相传、病程缩短、耳聋程度加重的特征。发生耳聋的年龄愈小，言语功能愈差。结论：应加强对遗传性聋的咨询，指导以及宣传工作。尽力减少或控制遗传性耳聋的发生率，对有家族遗传史者应定期进行听力学监测，对已发生耳聋者应及早配戴助听器并进行适当的言语训练。     

长期氧疗预防慢性阻塞性肺病所致感音神经性聋的效果

目的探讨长期氧疗(LTOT)对慢性阻塞性肺病患者听功能的调治作用。方法选择48例已确诊为慢性阻塞性肺病患者随机分为治疗组28例和对照组20例。治疗组给予长期氧疗,对照组未接受长期氧疗,随访观察3年。两组试验前后均行纯音测听、听性脑干反应测听(ABR)检查。采用配对t检验分析同组试验前后阈值的差异,t检验分析组间差异。结果治疗组治疗后与对照组之间以及对照组前后对比观察存在显著差异;治疗组治疗前与对照组之间以及治疗组前后对比观察无显著差异。结论持续氧疗可有效减缓慢性阻塞性肺病引起的感音神经性聋的发生。     

246例传导聋的手术治疗

目的 探讨传导聋的诊治方法，提高其诊治水平。方法 对随访的179例患者临床资料进行回顾性分析，根据病因不同采用不同术式治疗。结果 随访3～15月，疗效满意。结论 外耳道闭锁者尽可能取直入式径路，可减少术后术腔渗出、感染，术后据需要置入扩张管以防再狭窄、闭锁。单纯鼓膜穿孔而残边少或无者，行耳道切口作耳道鼓膜瓣后内植或夹层法修补成功率高。中耳腔、听骨链病变者应在彻底去除病灶后尽可能重建听力。     

A novel animal model of hearing loss caused by acute endoplasmic reticulum stress in the cochlea

Many stimuli such as ischemia, hypoxia, heat shock, amino acid starvation, and gene mutation, exhibit a cellular response called endoplasmic reticulum (ER) stress. ER stress induces expression of a series of genes, leading to cell survival or apoptosis. Previously, we found that in an animal model of hearing loss caused by acute mitochondrial dysfunction, several ER stress markers including C/EBP homologous protein were induced in the cochlear lateral wall. To elucidate the mechanism of hearing loss caused by ER stress, we established a novel animal model of hearing loss by perilymphatic perfusion of tunicamycin, an ER stress activator that inhibits N-acetylglucosamine transferases. Subacute and progressive hearing loss was observed at all sound frequencies studied, and stimulation of ER stress marker genes was noted in the cochlea. The outer hair cells were the most sensitive to ER stress in the cochlea. Electron microscopic analysis demonstrated degeneration of the subcellular organelles of the inner hair cells and nerve endings of the spiral ganglion cells. This newly established animal model of hearing loss from ER stress will provide additional insight into the mechanism of sensorineural hearing loss.     

基因芯片法检测自疑药源性耳聋患者基因突变35例

目的:对自疑药源性非综合征型耳聋患者进行中国人常见耳聋基因的突变分析,以明确其分子病因。方法:收集35名自疑非综合征药源性耳聋患者的外周血样本,常规方法提取基因组DNA,进行基因芯片分析。对突变患者的基因,进行PCR扩增,扩增产物经DNA测序分析,并与NCBI GenBank数据库进行比对,从而对耳聋相关基因的突变进行分析。结果:35名自疑非综合征耳聋患者中检出已知的mtDNA12SrRNA基因罕见致病突变C1494T 1例,占2.86%,其余为野生型或是其他基因突变。结论:在临床自疑药物性聋病患者中真正与线粒体基因突变相关的仅占少数,48临床开展药源性耳聋基因检测时,最好同时进行其他耳聋相关基因的检测,而基因芯片检测是其中一项很好的方法。     

单侧感音神经性耳聋患者听觉皮层的BOLD-fMRI研究

目的 利用血氧水平依赖功能磁共振(BOLD-fMRI)成像技术,探讨单侧感音神经性耳聋患者听觉皮层优势半球的变化及可能存在的功能重组.方法 选取苇度单侧长期感音神经性耳聋患者21例(13例左耳聋,8例右耳聋),采用Sparse设计进行正弦调幅音(AM)任务下的fMRI数据采集,实验刺激为500 Hz的载波频率,8 Hz的AM,耳聋患者健耳呈现.采用1.5 T超导型MRI成像系统,采集脑部的BOLD-fMRI数据后,通过SPM2软件对数据进行统计学分析,得到脑功能活动的图像.结果 单侧长期感音神经性耳聋患者健耳给声,双侧听觉皮层均有激活,但仍为对侧半球优势.结论 听觉中枢具有可塑性,单侧感音神经性耳聋患者听觉皮层存在着结构重组.     

突发性耳聋的治疗分析

目的：探讨高压氧在治疗突发性耳聋中的作用。方法：回顾性分析2008年之前5年间经广东省第二人民医院确诊为突发性耳聋的患者103例,经高压氧并辅助药物治疗的总体疗效。结果：103例患者中治愈22例,显效27例,有效41例,无效13例。总有效率87．4％（90／103）。并显示发病后就诊时间与听力损害程度对预后影响较大。结论：突发性耳聋以听力损伤程度轻或发病时间短的情况下为最有效治疗时期,高压氧辅助药物治疗能显著提高听力域。     

Drugs for hyperlipidaemia may slow down the progression of hearing loss in the elderly: A drug repurposing study

Hearing loss in the elderly causes communication difficulties, decreased quality of life, isolation, loneliness and frustration. The aim of this study was to identify the modifiable variables that may affect the progression of hearing loss in the elderly. A case‐control study was conducted using two data sets. Data were extracted from the health examination survey of Ajou University Hospital (2010‐2014) and the Korea National Health and Nutrition Examination Survey (2009‐2012) data sets. Audiometry data were evaluated according to variables such as age, sex and drug use for underlying diseases. Logistic regression analysis was performed on the entire study population, and middle‐aged and elderly groups using odds ratios (ORs). Factors including older age, female gender and diabetes mellitus were significantly associated with hearing levels in all age groups (OR [95% confidence interval, 95% CI], 0.375 [0.388‐0.415], 1.202 [1.195‐1.208], and 1.427 [1.183‐1.721], respectively). However, when the results from the middle‐aged and elderly groups were compared, medication for hyperlipidaemia had a significantly positive effect on the preservation of hearing in the elderly group (OR [95% CI], 0.713 [0.567‐0.897]), but not in the middle‐aged group (OR [95% CI], 0.967 [0.791‐1.183]). People, especially those in the elderly group, exposed to medication for hyperlipidaemia are likely to have better hearing than those not exposed to such drugs. Thus, drugs prescribed for hyperlipidaemia may maintain hearing in the elderly. However, to overcome potential confounding—by unmeasured variables—that is present in this study, further studies must be performed with more elaborate research design and methodology.     

长春西汀对突发性耳聋患者的疗效分析

目的：分析临床使用长春西汀治疗突发性耳聋患者的疗效。方法：选取2009年9月—2014年1月间诊治的突发性耳聋患者64例,将其随机分为对照组及治疗组（各组32例）,对照组患者予银杏达莫,静脉滴注;治疗组患者给予长春西汀,静脉滴注,两组患者均予加用激素及腺苷钴胺和高压氧协助治疗,10 d为一个疗程,比较两组患者的疗效。结果：治疗组患者耳聋治疗的总有效率为87.50%,对照组患者的总有效率为62.50%,经比较其差异有统计学意义（P〈0.05）;治疗组患者耳鸣的有效率为84.37%,对照组耳鸣的有效率为62.50%（P〈0.05）。结论：长春西汀可改善内耳循环,用于突发性耳聋的治疗,其疗效较为满意,不良反应较少。     

Sudden hearing loss subsequent to diarrhea: what is the missing link?

Sudden sensorineural hearing loss (SSNHL) is a debilitating condition with an incidence of nearly 20 per 100,000 in populations. Metronidazole-induced ototoxicity is an extremely rare etiology of SSNHL. In this report, we describe a young female with bilateral SSNHL due to oral use of metronidazole. A 23 years old female presented to the emergency department with acute bilateral hearing loss. We found out that her hearing loss had started 4 days after initiation of metronidazole which was administered for treatment of diarrhea. This case report shows that physicians should be aware of the uncommon side effects while prescribing metronidazole to patients in order to manage the possible adverse events on time.     

A case report of hearing loss post use of hydroxychloroquine in a HIV-infected patient

Objective

A case with reversible symmetrical sensorineural hearing loss following hydroxychloroquine therapy is described.

Case summary

A 57-year-old, human immunodeficiency virus (HIV) positive man was referred to the HIV clinic of Imam Khomeini Hospital, Tehran with chief complaint of bilateral slowly progressive hearing loss starting from two months ago. The man had history of rheumatoid arthritis diagnosed from 3 months ago and was administered hydroxychloroquine 200 mg and prednisolone 5 mg twice daily. Audiometry test showed moderate to severe neuronal hearing loss and reduced speech recognition in both ears of the patient. With suspicion of hydroxychloroquine-induced hearing loss, this drug was discontinued. After 2 months of hydroxychloroquine discontinuation, his audiometry findings were improved.

Discussion

A few cases of hydroxychloroquine-induced hearing loss have been reported. All of the cases were non-HIV positive individuals. Irreversible hearing loss was developed following long-term therapy with hydroxychloroquine. The present case was a HIV-positive man who developed hearing loss following short course (one month) hydroxychloroquine therapy and his problem was resolved following discontinuation of hydroxychloroquine and continuation of prednisolone.

Conclusions

Hydroxychloroquine-induced hearing loss may reversibly occur following short term therapy in HIV patients.     

CT及MRI在感音神经性耳聋患者行人工耳蜗植入术前的应用价值

目的 探讨CT及MRI在感音神经性耳聋（SNHL）患者行人工耳蜗植入（CI）术前的应用价值。方法 回顾分析2012年11月至2016年11月安徽医科大学第二附属医院收治的87例拟行CI的SNHL患者的CT及MRI图像,结合Sennaroglu分类法进行影像分类诊断。结果 87例SNHL患者的174耳中,耳蜗畸形10耳,前庭导水管扩大28耳,半规管畸形2耳,内听道畸形1耳,中耳炎患者7例。结论 不同影像学检查在SNHL患者CI术前能提供多种信息,均对临床诊治有重要的作用。     

高压氧辅助治疗突发性聋疗效观察

目的:观察高压氧辅助治疗突发性聋的疗效,并进一步探讨突发性聋的综合治疗方法。方法72例突发性聋患者随机分为高压氧组和对照组,均用药物治疗,高压氧组在常规药物治疗基础上行高压氧治疗,结果与对照组进行比较。结果:高压氧辅助治疗组的临床恢复疗效,与对照组比较有显著性差异(P<0.05)。结论:高压氧可作为一种辅助手段治疗突发性聋,效果显著。     

1型糖尿病患者听力损失的评价与分析

目的:研究1型糖尿病患者听力相关的常见症状以及听力损失相关危险因素。方法:受试者分两组。1型糖尿病组有30位确诊患者;对照组包含15位健康受试者。所有受试者均进行耳鼻喉科专科及血糖控制情况的问卷调查和听力检查(包括纯音测听、声导抗以及听性脑干反应)。结果:最常见的耳鼻喉科相关的症状为耳鸣与听力损失。有16.67%的患者(5例)表现为感觉神经听力损失,均为双侧高频损伤。这些患者平时血糖控制不佳。26.67%的患者(8例)ABR间期潜伏期I～III延迟。所有正常对照患者均无相关症状,其听力测试及ABR检查均正常。结论:在1型糖尿病患者中,最常见的耳鼻喉科相关的症状与体征为耳鸣与双耳对称的轻中度高频损伤。在1型糖尿病听力阈值正常的患者中,ABR间期潜伏期常延迟。     

高压氧综合治疗突发性耳聋的疗效观察

目的：探讨高压氧综合治疗突发性耳聋的疗效。方法：A组56例突发性耳聋患者行高压氧加药物联合治疗;B组53例突发性耳聋患者仅行药物治疗。结果：A组的有效率为89．1％,优于对照组的75．4％（P〈0．05）。听力损失〉70dB者的疗效（77．3％）低于听力损失45-70dB（95．2％）者。A组耳鸣治疗有效率（81．6％）高于B组（62．2％）,P〈0．05。结论：高压氧加药物联合治疗突发性耳聋疗效肯定,无明显不良发应,为临床治疗突发性耳聋较理想的方案。     

A mitochondrial targeting tetrapeptide Bendavia protects lateral line hair cells from gentamicin exposure

The hearing loss induced by aminoglycosides is caused by the permanent loss of mechanosensory hair cells of the inner ear. The aim of the present study is therefore to evaluate the protective effect of Bendavia, a novel antioxidant, on gentamicin‐induced hair cell damage in zebrafish lateral lines. The results demonstrated the pretreatment of Bendavia exhibited dose‐dependent protection against gentamicin in both acute and chronic exposure. We found that Bendavia at 150 μm conferred optimal protection from either acute or chronic exposure with ototoxin. Bendavia reduced uptake of fluorescent‐tagged gentamicin via mechanoelectrical transduction channels, suggesting its protective effects may be partially due to decreasing ototoxic molecule uptake. The intracellular death pathways inhibition triggered by gentamicin might be also included as no blockage of gentamicin was observed. Our data suggest that Bendavia represents a novel otoprotective drug that might provide a therapeutic alternative for patients receiving aminoglycoside treatment.     

静脉滴注七叶皂苷钠致听力下降

1例56岁男性患者因病毒性脑膜炎给予阿昔洛韦0.5 g溶于250 ml生理盐水,3次/d静脉滴注及甘露醇125ml,4次/d静脉滴注治疗.第5天加用七叶皂苷钠20 mg溶于250 ml生理盐水,1次/d静脉滴注,滴速60滴/min,约60 min输注完毕.输注完毕约8 h后,患者出现耳部闷胀不适、耳鸣及对声音分辨能力下降.次日耳部不适感和耳鸣消失,声音分辨能力下降无明显改善.纯音电测听检查示双耳高频听力中度受损,感音神经性听力减退.4 d后再次应用七叶皂苷钠,剂量及用法同前,约10 h后再次出现听力下降、耳部不适、耳鸣.次日耳部不适感及耳鸣均消失,但声音分辨能力下降无明显缓解.给予维生素C、复合维生素B,约2个月后患者听力明显恢复.     

脑白质病对先天性耳聋患儿人工耳蜗术后听觉言语恢复的影响

目的：探讨脑白质病对先天性耳聋患儿人工耳蜗术后听觉言语恢复的影响,为聋儿提供术前评价及术后恢复情况的评估。方法回顾性分析86例行人工耳蜗植入术的先天性耳聋患儿,年龄10月～6岁。术前行头颅常规 MRI 和内耳水成像,根据常规 MRI 表现分为脑白质病组和无脑白质病组,观察两组内耳畸形情况。术后半年采用听觉行为分级标准（CAP）和言语可懂度分级标准（SIR）对两组患儿的听力及言语恢复水平分别评分,并进行统计学分析比较。结果86例患者中22例存在脑白质病变,其中2例伴有内耳畸形;64例无脑白质病变,其中26例伴有内耳畸形。术后半年,脑白质病组 CAP 和 SIR 评分分别为（3．95±1．00）和（2．05±0．72）,无脑白质病组则分别为（5．72±1．31）和（3．08±0．74）,两组间差异显著。结论脑白质病是先天性耳聋患儿人工耳蜗植入后听觉感知及言语效果恢复的不利因素。     

南通地区感音神经性耳聋患者GJB2基因分析

目的 了解南通地区感音神经性耳聋人群的GJB2基因突变率及突变类型.方法 选择南通地区聋哑学校150例重度-极重度感音神经性耳聋学生外周血中提取白细胞DNA,以PCR法进行GJB2基因编码区测序及序列分析.结果 19.33%(29/150)学生的耳聋是由GJB2突变(双等位基因突变)引起,还有8.67%(13/150)的耳聋学生携带GJB2单杂合突变.结论 明确GJB2基因突变致聋对评估人工耳蜗植入后疗效及通过婚育指导来减少聋儿产生有重要意义.