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用于抗银屑病、维甲酸和防晒剂的动物试验。

Animal assays for anti-psoriatic, retinoid and sun protective agents.

作者信息

Lowe N J, Connor M J, Ashton R, Wortzman M

出版信息

Br J Dermatol. 1984 Jul;111 Suppl 27:98-108. doi: 10.1111/j.1365-2133.1984.tb15587.x.

Abstract

It is possible to evaluate different dermatological therapeutic agents intended for human use in a variety of animal assays. This review will discuss some of these assays, and attempt to correlate animal and human skin responses. Psoriasis is a disease where changes in epidermal proliferation may be an important factor. It is possible to assay potential anti-psoriatic agents by measuring their ability to suppress DNA synthesis in the epidermis of hairless mice. This assay is predictive of the anti-psoriatic effectiveness of numerous agents including a variety of anti-proliferative drugs and anthralin, and has been used to evaluate the potential efficacy of purified coal tar shampoos and body preparations. The activity of the polyamine biosynthesis enzyme ornithine decarboxylase (ODC) is elevated in psoriatic skin, and it is induced in mouse epidermis by tape stripping. Retinoids can inhibit the induction of ODC activity, and this inhibition may be used to evaluate novel synthetic retinoids. Retinoids have beneficial effects on the abnormal keratinization found in various diseases. Rhino mice have multiple keratin-filled epidermal utricles, and the size of these is reduced by retinoid treatment. Observing the changes in the size of the utricles can be utilized to evaluate the effects of retinoids on keratinization. Sunscreen agents are tested on human volunteers by observing their ability to inhibit the erythema induced by exposure to solar-simulated light, to obtain a sun protection factor (SPF). It is possible to utilize the ability of sunscreens to inhibit other actinic-induced changes in the skin using animals. Parameters that may be measured include changes in DNA synthesis and ODC activity in the epidermis following ultraviolet irradiation. Some of these assays correlate well with human SPF determinations.

摘要

在各种动物试验中评估用于人类的不同皮肤科治疗药物是可行的。本综述将讨论其中一些试验,并尝试关联动物和人类皮肤反应。银屑病是一种表皮增殖变化可能是重要因素的疾病。通过测量潜在抗银屑病药物抑制无毛小鼠表皮中DNA合成的能力,可以对其进行检测。该试验可预测多种药物(包括各种抗增殖药物和蒽林)的抗银屑病效果,并已用于评估纯化煤焦油洗发水和身体护理产品的潜在疗效。多胺生物合成酶鸟氨酸脱羧酶(ODC)的活性在银屑病皮肤中升高,并且通过胶带剥离在小鼠表皮中被诱导。维甲酸可以抑制ODC活性的诱导,这种抑制作用可用于评估新型合成维甲酸。维甲酸对各种疾病中发现的异常角质化有有益作用。犀牛小鼠有多个充满角蛋白的表皮小囊,维甲酸治疗可减小其大小。观察小囊大小的变化可用于评估维甲酸对角质化的影响。防晒剂通过观察其抑制暴露于模拟太阳光诱导的红斑的能力在人类志愿者身上进行测试,以获得防晒系数(SPF)。利用动物可以检测防晒剂抑制皮肤中其他光化诱导变化的能力。可测量的参数包括紫外线照射后表皮中DNA合成和ODC活性的变化。其中一些试验与人类SPF测定结果相关性良好。

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