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豚鼠中耳滴注庆大霉素和链霉素:选择性耳毒性的形态学评估

Middle ear instillation of gentamicin and streptomycin in chinchillas: morphologic appraisal of selective ototoxicity.

作者信息

Chen J M, Kakigi A, Hirakawa H, Mount R J, Harrison R V

机构信息

Department of Otolaryngology, University of Toronto, Ontario.

出版信息

J Otolaryngol. 1999 Jun;28(3):121-8.

Abstract

OBJECTIVE

To determine selective cochlear and vestibular ototoxicity of two aminoglycoside antibiotics (gentamicin and streptomycin) in the chinchilla model. Middle ear application of these agents mirrors the clinical practice of chemical vestibular ablation used in Meniere's disease.

BACKGROUND

Middle ear instillation of gentamicin or streptomycin has become a popular form of vestibular ablative treatment for disabling Meniere's disease. The vestibular selectivity of these two drugs applied in this fashion has clinical support but is not fully established in humans. Our understanding in this regard has largely been limited to animal models exposed to systemic infusion of aminoglycosides.

METHOD

Ten chinchillas underwent left middle ear instillation of one of three agents using variable dosing schedules: gentamicin (n = 6), streptomycin (n = 2), and saline (n = 2) as control. Animals were sacrificed for temporal bone studies using scanning electron microscopy. Morphologic changes in the cochlear and vestibular neuroepithelia were identified.

RESULTS

Widespread cochlear and vestibular neuroepithelial injuries were observed with both gentamicin and streptomycin. Contralateral ototoxicity was variable and not related to the total dose of drug delivered. The effect of these two aminoglycosides on the dark cells of the vestibular system appeared negligible.

CONCLUSION

We were unable to confirm the selective damage of vestibular end-organ in the chinchilla by either gentamicin or streptomycin, a phenomenon that is generally perceived to occur in humans. Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.

摘要

目的

在毛丝鼠模型中确定两种氨基糖苷类抗生素(庆大霉素和链霉素)对耳蜗和前庭的选择性耳毒性。这些药物的中耳应用反映了梅尼埃病中化学性前庭消融的临床实践。

背景

庆大霉素或链霉素的中耳滴注已成为治疗致残性梅尼埃病的一种流行的前庭消融治疗方式。以这种方式应用的这两种药物的前庭选择性有临床依据,但在人类中尚未完全确立。我们在这方面的认识很大程度上局限于全身输注氨基糖苷类药物的动物模型。

方法

10只毛丝鼠接受了三种药物之一的左耳中耳滴注,采用可变给药方案:庆大霉素(n = 6)、链霉素(n = 2)和生理盐水(n = 2)作为对照。使用扫描电子显微镜对动物进行颞骨研究并处死。确定耳蜗和前庭神经上皮的形态学变化。

结果

庆大霉素和链霉素均观察到广泛的耳蜗和前庭神经上皮损伤。对侧耳毒性各不相同,且与给药的总剂量无关。这两种氨基糖苷类药物对前庭系统暗细胞的影响似乎可以忽略不计。

结论

我们无法证实庆大霉素或链霉素对毛丝鼠前庭终末器官的选择性损伤,而这种现象通常被认为在人类中会发生。与其他小型哺乳动物一样,毛丝鼠可能不是研究人类耳毒性的理想模型。

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