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鼓室内治疗新实验模型的初步结果

Preliminary Results of a New Experimental Model for Intratympanic Treatment.

作者信息

Aykal Kamil, Ardıç Fazıl Necdet, Tümkaya Funda, Yücel Emrah, Akarsu Mehri, Kara Cüneyt Orhan, Erdem Emin

机构信息

Department of Otorhinolaryngology, Pamukkale University School of Medicine, Denizli, Turkey.

Department of Chemistry, Pamukkale University School of Medicine, Denizli, Turkey.

出版信息

Turk Arch Otorhinolaryngol. 2018 Dec;56(4):188-192. doi: 10.5152/tao.2018.3467. Epub 2018 Dec 1.

DOI:10.5152/tao.2018.3467
PMID:30701112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6340320/
Abstract

OBJECTIVE

Corticosteroids have been applied via transtympanic route for a long time to treat the inner ear disorders. A few animal models were used to answer the questions, "How much drug goes into the inner ear?" and "How far does the drug reach through the scala tympani and/or scala vestibuli?" However, the cerebrospinal fluid contamination poses a major problem. The aims of this study were to create a new sampling model showing the dexamethasone distribution in the inner ear and to provide more reliable data about drug concentrations.

METHODS

Ten Hartley strain albino guinea pigs that weighted between 400 and 600 g were used. After dexamethasone application to the left ear, they were sacrificed at two time points: after 0.5 hours (Exp 1) and after 2 hours (Exp 2). The temporal bones were immediately dissected and put into liquid nitrogen for freezing. The apex, second turn, and basal turns of the cochlea and vestibule were separated, while the bone was in the frozen state. The samples were prepared and measured with ultraviolet (UV) spectroscopy.

RESULTS

The total amount of dexamethasone was statistically higher in the left ear than the control ear. Although the basal turn and vestibule were the most prominent parts, there was no statistical difference between the different parts of the inner ear at 0.5 hours. The vestibule and the apex showed the highest level of dexamethasone at 2 hours.

CONCLUSION

Although the model has some limitations, it can measure dexamethasone concentrations and show the time variability in the inner ear.

摘要

目的

长期以来,皮质类固醇一直通过经鼓膜途径应用于治疗内耳疾病。曾使用一些动物模型来回答“有多少药物进入内耳?”以及“药物通过鼓阶和/或前庭阶能到达多远?”这些问题。然而,脑脊液污染是一个主要问题。本研究的目的是创建一个新的采样模型,以显示地塞米松在内耳中的分布,并提供关于药物浓度的更可靠数据。

方法

使用10只体重在400至600克之间的哈特利白化豚鼠。在向左耳应用地塞米松后,在两个时间点将它们处死:0.5小时后(实验1)和2小时后(实验2)。立即解剖颞骨并放入液氮中冷冻。在骨头处于冷冻状态时,分离耳蜗和前庭的顶部、第二圈和基部。制备样品并用紫外光谱法进行测量。

结果

地塞米松的总量在左耳中统计学上高于对照耳。尽管基部和前庭是最显著的部位,但在0.5小时时内耳不同部位之间没有统计学差异。在2小时时,前庭和顶部显示出最高水平的地塞米松。

结论

尽管该模型存在一些局限性,但它可以测量地塞米松浓度并显示内耳中的时间变化。

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本文引用的文献

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Otol Neurotol. 2012 Jun;33(4):660-5. doi: 10.1097/MAO.0b013e318254501b.
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Entry of substances into perilymph through the bone of the otic capsule after intratympanic applications in guinea pigs: implications for local drug delivery in humans.豚鼠鼓室内给药后物质通过耳囊骨进入外淋巴:对人类局部药物递送的意义
Otol Neurotol. 2009 Feb;30(2):131-8. doi: 10.1097/mao.0b013e318191bff8.
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Inner ear drug delivery for auditory applications.用于听觉应用的内耳药物递送。
Adv Drug Deliv Rev. 2008 Dec 14;60(15):1583-99. doi: 10.1016/j.addr.2008.08.001. Epub 2008 Sep 21.
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Otol Neurotol. 2008 Apr;29(3):401-6. doi: 10.1097/MAO.0b013e318161aaae.
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The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration.全身和局部给药后地塞米松和甲泼尼龙在外淋巴液和血浆中的药代动力学特征。
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Laryngoscope. 2007 Jul;117(7):1191-8. doi: 10.1097/MLG.0b013e318058a06b.
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