抗生素89－07与奈替米星对豚鼠耳毒性的比较

９２只豚鼠分别肌注４种剂量的抗生素８９－０７、ＮＴＬ及生理盐水，２８ｄ后通过电生理、病理形态学检查，比较抗生素８９－０７与ＮＴＬ对豚鼠的耳毒性。结果显示：抗生素８９—０７与ＮＴＬ对听性脑干电反应阈值无显著影响。抗生素８９－０７较ＮＴＬ对前庭功能影响稍轻。耳蜗病变从扫描电镜、耳蜗铺片所见抗生素８９－０７较ＮＴＬ轻。内耳切片观察两药无显著区别．前庭病变各剂量总体相比抗生素８９－０７较ＮＴＬ轻。     

中药防治氨基糖苷类药物耳毒性的研究进展

该文介绍了氨基糖苷类抗生素耳毒性的发生机制,回顾了中药对氨基糖苷类抗生素耳毒性防治作用的研究资料,总结并分析了10味中药(川芎、丹参、刺五加、当归、黄芩、葛根、茯苓、骨碎补、儿茶素、月见草)和多种复方制剂(复聪片、耳聋左慈丸、金匮肾气丸、天鼓冲剂、复方丹参、补肾聪耳片等)对氨基糖苷类抗生素实验性耳毒性的防治作用及可能机制。     

氨基苷类药物耳毒性的治疗策略

临床应用的氨基苷类抗生素能损伤内耳毛细胞.引起患者听力损伤.其损伤机制是在耳蜗中产生自由氧,从而激活毛细胞死亡通路,继发细胞凋亡.目前,保护内耳免受耳毒性药物损伤的策略一.     

非氨基糖苷类药物引发耳毒性文献的回顾性分析

目的 回顾分析药源性耳毒性的药品及其作用机制.方法 检索1998年1月～ 2010年12月国内医药期刊报道的病例进行统计分析.结果 166例病例纳入分析,引发耳毒性的非氨基糖苷类药物种类各异,主要包括抗感染药,利尿药,水杨酸类制剂、麻醉药、抗肿瘤药,儿童,老年人,肝肾功能不全者易引发耳毒性,1～30天为高发期.结论 非氨基糖苷类药物引发耳毒性可造成耳鸣、耳聋、眩晕和平衡失调,临床医务人员应引起重视.     

氨基糖苷类药物耳毒性的斑马鱼模型的研究

氨基糖苷类抗生素因其抗菌谱广、抗菌能力强,半个多世纪以来一直是临床上常用的抗菌素之一。但氨基糖苷类抗生素具有很强的耳毒和肾毒作用,在药物致聋因素中排在首位。本研究以庆大霉素(gentamycin)、新霉素(neomycin)、链霉素(streptomycin)等3种氨基糖苷类抗生素为代表性药物,研究其对斑马鱼胚胎发育的毒性作用和对幼体毛细胞的损伤作用,并探索了该损伤与听觉相关基因之间的联系。结果显示:①3种药物的致死作用都具有明显的浓度依赖性,其致死作用的强弱顺序为链霉素>新霉素>庆大霉素;②3种药物处理的5 dpf(day past fertilization)幼体出现身体失衡及体位异常,以及耳囊结构的异常变化;③毛细胞染色实验可观察到,3种药物作用的毛细胞和神经丘均出现明显的损伤和数量减少;④与听觉器官发育相关的基因eya1、val、otx2、dlx6a均随3种抗生素药物浓度的升高,出现差异性的表达水平下调。本研究首次探索了这3种耳毒性氨基糖苷类抗生素处理与斑马鱼听囊结构和听觉基因表达的相关性;并证明利用斑马鱼建立简便、准确、直观、快速地检测药物耳毒性的模型和检测方法的可行性。     

中耳应用头孢噻甲羧肟对听性脑干反应的影响及耳毒性评估

30只豚鼠中耳分别注入不同浓度的头孢噻甲羧肟（CAZ）生理盐水溶液，连用一周后停药两周，观察比较听性脑子反应（ABR）Ⅲ波反应阈变化。结果；20％CAZ组14耳中有7耳ABR反应阈明显改变，提高15～30dB；5％CAZ组13耳中仅1耳ABR反应阈提高15dB。表明中耳应用高浓度CAZ有一定的耳毒性，而低浓度CAZ则可认为是安全的。     

耳声发射与自动听性脑干反应联合应用对新生儿听力筛查的临床意义

目的 探究耳声发射与自动听性脑干反应联合应用对新生儿听力筛查的临床意义.方法 选择2015年8月至2016年8月在本院接受听力筛查的320例新生儿作为研究对象,将新生儿按照入院顺序分为对照组和研究组,每组患儿160例,320耳.对照组行耳听发射筛查,研究组新生儿行耳声发射与自动听性脑干反应联合应用.对比两组新生儿筛查结果,之后对未通过筛查患儿进行复诊,对比两组患儿的诊断准确率以及假阳性率.结果 研究组新生儿筛查通过例数(80.00％比90.62％)以及耳数(83.13％比91.88％)明显低于对照组,两组比较差异均有统计学意义(均P＜0.05).研究组患儿的诊断确诊率为90.74％,对照组为57.69％,研究组确诊率高于对照组(P＜0.05).研究组患儿假阳性率明显低于对照组(3.60％比12.85％),两组比较差异有统计学意义(P＜0.05).结论 在对新生儿行听力筛查时,选择耳声发射联合自动听性脑干反应具有更高的准确率,且假阳性率较低.     

氨基糖甙类药物耳毒性反应的诱发电位(BAEP)监测分析

应用常规剂量氨基糖甙类药物对23例患儿进行BAEP监测研究,以了解此类药物的耳毒性及远期影响。结果发现:23例患儿中,1例听力稍差,18例22只耳BAEP异常。     

基于斑马鱼模型的4种氨基糖苷类药物的耳肾毒性比较

氨基糖苷类药物的耳肾毒性限制了其临床应用.本研究使用斑马鱼模型评价地贝卡星及其衍生物阿贝卡星、庆大霉素C1a及其衍生物依替米星的胚胎毒性和耳肾毒性.结果 表明,4种药物的胚胎致死性大小依次为:阿贝卡星＞依替米星＞庆大霉素C1a和地贝卡星.肾毒性大小的排序为:地贝卡星＞庆大霉素C1a＞阿贝卡星＞依替米星.毛细胞耳毒性大小...     

Comparative ototoxicity of netilmicin, gentamicin, and tobramycin in cats

Netilmicin, a semisynthetic aminoglycoside antibiotic, is less ototoxic in a variety of species than other aminoglycosides currently in therapeutic use. In this study, mixed-breed cats (four/group) were given daily sc injections of netilmicin (20, 40, and 80 mg/kg), gentamicin (20 and 40 mg/kg), or tobramycin (20, 40, and 80 mg/kg) for up to 30 weeks or until ototoxicity was observed. The animals were examined throughout the study for effects on cochlear and vestibular function. Hematologic, serum chemical, and drug-serum (24-hr postdose) assays were performed at approximate monthly intervals during the dosing period. The cochleae, kidneys, and liver were examined microscopically. The mean number of dose days required to produce vestibulotoxic effects, demonstrated by impaired righting reflex or locomotor ataxia, was from 41 to 61 in cats dosed with tobramycin (40 and 80 mg/kg) or gentamicin. No vestibular dysfunction was observed in any of the netilmicin 20-mg/kg-dosed cats, in two cats each of the tobramycin 20-mg/kg and netilmicin 40-mg/kg groups, and in one netilmicin 80-mg/kg-dosed animal. Histologic examination of the cochleae revealed degeneration of the hair cells and supporting sensory structures in the majority of cats dosed with gentamicin at 20 and 40 mg/kg and tobramycin at 40 and 80 mg/kg. Less than 50% of the tissues from cats of the tobramycin 20-mg/kg and netilmicin 40- and 80-mg/kg-dosed groups had similar degenerative cochlear changes. No cochlear damage was noted in any of the cats given netilmicin at 20 mg/kg. Results of the clinical laboratory determinations were generally unremarkable. Proximal tubular degeneration was the principal finding observed in the kidneys of the animals. Under the conditions of this study, at least a twofold (vestibular) to fourfold (cochlear) relative safety margin for ototoxicity was established in favor of netilmicin over tobramycin and gentamicin.     

Comparative ototoxicity of amikacin,gentamicin, netilmicin,and tobramycin in guinea pigs

The ototoxicity of amikacin, gentamicin, netilmicin, and tobramycin in guinea pig, given daily sc doses for 3 weeks, was assessed and compared. Preyer pinna reflex evaluation and electrophysiologic auditory responses, such as brain stem-evoked responses and whole nerve action potential, as well as surface examination of cochlear sensory epithelia, were conducted. A direct dose-dependent inner ear toxicity was demonstrated with amikacin, gentamicin, and tobramycin in terms of time of onset and severity of final damage. In contrast, netilmicin did not cause significant changes in cochlear function even at the highest dosage level tested. The threshold dose required to produce injury, based on the total dose administered during the 3-week period, indicated that the ototoxic potential for tobramycin and gentamicin was very similar and about four times higher than that of amikacin. However, based on the extrapolated clinical doses, the ototoxic potential of gentamicin, tobramycin, and amikacin at the recommended human therapeutic dose would be the same. In contrast, netilmicin in these guinea pig models was very well tolerated, and no signs of physiologic or morphologic cochlear damage were demonstrated, suggesting that netilmicin has less ototoxic liability in the human than the other three aminoglycosides.     

抗生素89－07、庆大霉素和阿米卡星对豚鼠连续肌注15天的耳毒性初步比较

从功能与形态学两方面比较抗生素８９－０７、庆大霉素（ＧＭ）、阿米卡星（ＡＭＫ）对豚鼠耳蜗的影响，在豚鼠连续肌注１５天，停药１４天后，发现２００ｍｇ／（ｋｇ·ｄ）组庆大霉素与阿米卡星对耳蜗毛细胞平均损伤享为６３％与１０％，而相同剂量的抗生素８９－０７平均损伤率仅０．３％，说明抗生素８９－０７耳毒性极小，比ＧＭ和ＡＭＫ更为安全。     

毛细管区带电泳-间接紫外检测氨基糖苷类抗生素中硫酸根

目的:用毛细管区带电泳-间接紫外检测技术检测氨基糖苷类抗生素中硫酸根。方法:采用非涂层弹性石英毛细管;背景电解质为含0.2 mmol.L-1十六烷基三甲基溴化铵的15 mmol.L-1铬酸水溶液(用三羟甲基氨基甲烷调节pH至8.1);操作电压:-20 kV;检测波长:276 nm(间接检测);电泳过程中在进样端始终外加适当的压力使基线稳定。结果:本文方法的线性范围为45～150μg.mL-1;定量限约为6μg.mL-1;硫酸根与内标峰面积比的RSD为0.6%(n=10);测定结果与采用英国药典方法的测定结果一致。结论:本方法适用于对氨基糖苷类抗生素中的硫酸根的测定。     

Hearing loss,lead (Pb) exposure,and noise: a sound approach to ototoxicity exploration

To determine the state of the research on ototoxic properties of Pb, evaluate possible synergistic effects with concurrent noise exposure, and identify opportunities to improve future research, we performed a review of the peer-reviewed literature to identify studies examining auditory damage due to Pb over the past 50 years. Thirty-eight studies (14 animal and 24 human) were reviewed. Of these, 24 suggested potential ototoxicity due to Pb exposure, while 14 found no evidence of ototoxicity. More animal studies are needed, especially those investigating Pb exposure levels that are occupationally and environmentally relevant to humans. Further investigations into potential interactions of Pb in the auditory system with other hazards and compounds that elicit ototoxicity are also needed in animal models. To better assess the effects of Pb exposure on the human auditory system and the possibility of a synergism with noise, future epidemiological studies need to carefully consider and address four main areas of uncertainty: (1) hearing examination and quantification of hearing loss, (2) Pb exposure evaluation, (3) noise exposure evaluation, and (4) the personal characteristics of those exposed. Two potentially confounding factors, protective factors and mixtures of ototoxicants, also warrant further exploration.     

Comparative Ototoxic Effects of RU 25434, Amikacin and Neomycin in Guinea-pigs

Abstract The ototoxic effects of RU 25434, a new semi-synthetic aminoglycoside antibiotic, were compared to those of amikacin and neomycin. Experiments were performed in adult and new-born guinea-pigs, ototoxicity being assessed by Preyer's reflex response and the measurement of the cochlear microphonic potentials at the end of treatment. The well known ototoxicity of neomycin was observed and RU 25434 appeared to be relatively less toxic than amikacin. The use of new-born guinea-pigs seems to be particularly suitable for this type of study because of their apparent sensitivity to ototoxicity.     

抗生素89—07,庆大霉素和阿米卡星的耳毒性比较

采用听性脑干电反应，眼震电图，结合火棉胶切片，耳蜗铺片琥珀酸脱氢酶染色方法和扫描电等形态学观察。综合主人抗生素８９－０７与阿米卡星、庆大霉素的耳毒性。结果表明：ＧＭ１００ｍｇ确有耳蜗系和前庭系毒性；ＡＭＫ２００ｍｇ对耳蜗第有轻度损伤，而抗生素８９－０７ ２５、５０、１００ｍｇ对耳蜗均无损伤。     

Pharmacokinetics of sisomicin in patients with normal and impaired renal function; its efficacy in urinary tract infection

Summary Serum concentration, biological half-life, distribution space and serum clearance of sisomicin, a new aminoglycoside antibiotic, have been studied in twenty-three patients in comparison with the pharmacokinetics of¹²⁵I-labelled iothalamate, a compound only filtered by the kidney. 10 patients had normal or borderline abnormal serum creatinine (<1,5 mg/100 ml), 8 had various degrees of renal insufficiency (serum creatinine 1.7 – 9.6 mg/100 ml) and 6 were being treated by intermittent haemodialysis. After intravenous injection of sisomicin 1 mg/kg body weight in patients with normal or borderline renal function its half-life was 3.5 h, very similar to that of iothalamate, 3.2 h. The mean distribution space was 20.1 % per cent of body weight; iothalamate, 23.7 %. In patients with renal insufficiency there was a positive correlation between serum creatinine level and the half-life of sisomicin, and an even stronger correlation between the clearances of iothalamate and sisomicin. In patients dependent on haemodialysis, the mean serum half-life between dialysis was 40 h, compared to approximately 100 hours for iothalamate, which implies additional extrarenal clearance or tubular secretion of sisomicin. The results of pharmacokinetic studies indicated that a regime of sisomicin 1 mg/kg every 8 to 12 hours in patients with normal renal function would result in serum and urine levels sufficiently high to treat most urinary tract infections. In patients with impaired renal function the dosage interval should be increased according to the serum creatinine level, and in patients dependent on haemodialysis one standard dose at the end of each dialysis period should suffice. 9 patients with a chronic urinary tract infection severely complicated by an underlying disease were treated according to this dosage regimen with a satisfactory bacteriological and clinical result. No adverse reactions or signs of accumulation were observed.