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太空环境中的时辰药理学问题。

Chronopharmacologic issues in space.

作者信息

Cornélissen G, Zaslavskaya R M, Kumagai Y, Romanov Y, Halberg F

机构信息

University of Minnesota, Minneapolis 55455.

出版信息

J Clin Pharmacol. 1994 Jun;34(6):543-51. doi: 10.1002/j.1552-4604.1994.tb02005.x.

Abstract

Times of heightened susceptibility are expressed by nonrandom patterns in the incidence of various diseases, not only along the scale of a day but also of a week and a year. Whereas these rhythms can be synchronized by the environment, their endogenicity is revealed by their persistence in the absence of time cues with a period slightly but statistically significantly different from the environmental match. In the case of some circadians, the gene involved has been identified and heritabiliy in humans determined by studies on twins. Vital signs are now amenable to automatic monitoring around the clock. When analyzed by chronobiologic software, the data provide information regarding the given individual's time structure (chronome). Such physiologic monitoring serves the multiple purposes of deriving time-specified reference norms on the basis of which rhythm alteration can detect an elevated risk early, thus prompting timely preventive action and timed treatment whenever warranted. For long journeys in space, the design of a multi-disease prophylactic pill poses a chronopharmacologic challenge. Drugs such as aspirin and carnitine, used for the prevention of strokes, myocardial infarctions and depression, all show striking chronome-dependent effects which can determine not only the presence or the absence of a desired effect, but even yield effects in opposite directions.

摘要

易感性增强的时期通过各种疾病发病率的非随机模式表现出来,不仅体现在一天的时间段内,还体现在一周和一年的时间段内。虽然这些节律可以与环境同步,但其内生性表现为在没有时间线索的情况下依然持续存在,其周期与环境匹配略有差异但在统计学上具有显著意义。在某些昼夜节律的情况下,相关基因已被确定,并且通过对双胞胎的研究确定了人类的遗传性。生命体征现在可以进行全天候自动监测。当通过时间生物学软件进行分析时,这些数据提供了有关特定个体时间结构(时间组)的信息。这种生理监测具有多种用途,即得出特定时间的参考标准,在此基础上,节律改变能够早期检测出风险升高,从而在必要时及时采取预防措施和定时治疗。对于长时间的太空旅行,设计一种预防多种疾病的药丸带来了时间药理学上的挑战。用于预防中风、心肌梗死和抑郁症的药物,如阿司匹林和肉碱,都显示出显著的时间组依赖性效应,这不仅可以决定是否产生预期效果,甚至可能产生相反方向的效果。

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