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甲状腺色素沉着与米诺环素治疗

Thyroid gland pigmentation and minocycline therapy.

作者信息

Gordon G, Sparano B M, Kramer A W, Kelly R G, Iatropoulos M J

出版信息

Am J Pathol. 1984 Oct;117(1):98-109.

PMID:6435454
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1900569/
Abstract

Thyroid pigments in black thyroid glands from minocycline-treated patients were compared by light and electron microscopy, histochemistry, and energy-dispersive x-ray analysis with minocycline-induced pigment in thyroid glands of laboratory animals, and with naturally occurring lipofuscins in untreated laboratory animals and humans. All thyroid samples examined contained nonbirefringent, Schmorl-positive pigment. However, the pigments in black thyroids from minocycline-treated patients resembled lipofuscins of untreated humans since both fluoresced and were Ziehl-Neelsen- and Sudan IV-positive. Minocycline induced pigment in rats was nonfluorescent and Ziehl-Neelsen- and Sudan IV-negative. Ultrastructurally, pigments in black thyroid glands of minocycline-treated humans resembled lipofuscins in untreated humans, and initial elemental analyses yielded similar spectra. Repeated analyses of the most electron-dense pigment deposits yielded spectra that resembled those of minocycline-induced pigment in laboratory animals-ie, both contained calcium. Black thyroid glands associated with minocycline administration contained predominantly lipofuscins with a small amount of another, possibly minocycline-related pigment. The absence of functional changes in patients and animals given minocycline suggests that discoloration of the thyroid gland associated with minocycline administration is innocuous. This is further supported by the lack of documented changes in thyroid physiology in patients that have received tetracyclines for a variety of indications in the last 30-odd years since their introduction to therapy.

摘要

通过光学显微镜和电子显微镜、组织化学以及能量色散X射线分析,对米诺环素治疗患者黑色甲状腺中的甲状腺色素,与实验动物甲状腺中米诺环素诱导的色素,以及未治疗实验动物和人类中天然存在的脂褐素进行了比较。所有检查的甲状腺样本均含有非双折射、Schmorl阳性色素。然而,米诺环素治疗患者黑色甲状腺中的色素类似于未治疗人类的脂褐素,因为两者都发荧光,且齐-尼氏染色和苏丹IV染色均为阳性。米诺环素诱导的大鼠色素不发荧光,齐-尼氏染色和苏丹IV染色均为阴性。超微结构上,米诺环素治疗的人类黑色甲状腺中的色素类似于未治疗人类的脂褐素,初步元素分析产生了相似的光谱。对电子密度最高的色素沉积物进行反复分析,得到的光谱类似于实验动物中米诺环素诱导的色素的光谱——即两者都含有钙。与米诺环素给药相关的黑色甲状腺主要含有脂褐素以及少量另一种可能与米诺环素相关的色素。给予米诺环素的患者和动物没有功能变化,这表明与米诺环素给药相关的甲状腺变色是无害的。自四环素引入治疗以来的30多年里,接受四环素治疗各种疾病的患者甲状腺生理学没有记录到变化,这进一步支持了这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/5cd72e0d1944/amjpathol00175-0115-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/1c0b062a1fee/amjpathol00175-0111-a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/11fbe6b030e2/amjpathol00175-0115-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/5cd72e0d1944/amjpathol00175-0115-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/1c0b062a1fee/amjpathol00175-0111-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/52657c98c413/amjpathol00175-0112-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/9a35c35ce38d/amjpathol00175-0113-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/1e9862d9b114/amjpathol00175-0113-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/0b7f02e3ab40/amjpathol00175-0114-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d0/1900569/11fbe6b030e2/amjpathol00175-0115-a.jpg
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Black thyroid.黑色甲状腺
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Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings.尽管临床前研究结果不利,但药物研发仍取得成功 第1部分:解决问题的流程及最重要的发现

本文引用的文献

1
THE CHRONIC ORAL TOXICITY OF OXYTETRACYCLINE HC1 AND TETRACYCLINE HC1 IN THE RAT, DOG AND PIG.盐酸土霉素和盐酸四环素对大鼠、狗和猪的慢性口服毒性
Ind Med Surg. 1964 Nov;33:787-806.
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The mechanism of iodination reactions in thyroid glands.甲状腺中碘化反应的机制。
Endocrinology. 1961 Apr;68:671-9. doi: 10.1210/endo-68-4-671.
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Ultrastructural and x-ray microanalytical observations of minocycline-related hyperpigmentation of the skin.米诺环素相关皮肤色素沉着的超微结构及X射线微分析观察
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[Therapy related alterations to the thyroid gland].[与治疗相关的甲状腺改变]
Pathologe. 2006 Feb;27(1):13-8. doi: 10.1007/s00292-005-0813-y.
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Black thyroid: report of an autopsy case.黑色甲状腺:一例尸检病例报告
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Follicular Carcinoma Associated with Minocycline-Induced Black Thyroid.与米诺环素诱导的黑色甲状腺相关的滤泡癌
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Histologic, immunohistochemical, and ultrastructural findings in a case of minocycline-associated "black thyroid".一例米诺环素相关“黑色甲状腺”的组织学、免疫组织化学及超微结构 findings(此处“findings”未准确对应中文,意译为“表现”等更合适,但按要求保留英文)
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Hyperpigmentation associated with oral minocycline.与口服米诺环素相关的色素沉着。
Br J Dermatol. 1982 Jul;107(1):95-102. doi: 10.1111/j.1365-2133.1982.tb00296.x.
5
Skin pigmentation secondary to minocycline therapy.米诺环素治疗引起的皮肤色素沉着。
Arch Dermatol. 1980 Nov;116(11):1262-5.
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Minocycline-induced pigmentation at sites of cutaneous inflammation.米诺环素诱导的皮肤炎症部位色素沉着。
JAMA. 1980 Sep 5;244(10):1103-6.
7
The black thyroid associated with minocycline therapy. A local manifestation of a drug-induced lysosome/substrate disorder.与米诺环素治疗相关的黑色甲状腺。药物诱导的溶酶体/底物紊乱的局部表现。
Am J Clin Pathol. 1983 Jun;79(6):738-46. doi: 10.1093/ajcp/79.6.738.
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Minocycline and black thyroid.米诺环素与黑色甲状腺。
JAMA. 1983 Apr 8;249(14):1887.
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The black thyroid. Its relation to minocycline use in man.黑色甲状腺。它与人类使用米诺环素的关系。
Arch Pathol Lab Med. 1983 Apr;107(4):173-7.
10
Systemic pigmentation from tetracycline and minocycline therapy.四环素和米诺环素治疗引起的全身性色素沉着。
Arch Dermatol. 1983 Jan;119(1):1-2. doi: 10.1001/archderm.119.1.1.