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转化毒理学:综合研究策略的发育重点。

Translational toxicology: a developmental focus for integrated research strategies.

机构信息

Quintiles, Inc, North Carolina State University; Wake Forest University; Duke University Medical Center, Morrisville, NC, USA.

出版信息

BMC Pharmacol Toxicol. 2013 Sep 30;14:51. doi: 10.1186/2050-6511-14-51.

Abstract

BACKGROUND

Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean?

DISCUSSION

Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development.

SUMMARY

Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.

摘要

背景

毒理学研究环境暴露对各种形式生命的潜在不良影响,而临床毒理学通常侧重于人类健康影响,那么相对较新的术语“转化毒理学”应该意味着什么呢?

讨论

我们的观点是,转化毒理学的核心概念必须包含毒理学和流行病学的现有原则,但必须以开发安全有效的干预措施为目标,超越单纯减少或避免暴露,以预防、减轻或逆转暴露对人类健康的不良影响。毒理学领域现在已经到了一个地步,即多个生物医学研究和信息技术领域的进步使我们能够直接影响人类健康,实现根本性的转变。转化毒理学必须包含以下四个行动要素:1)评估整个生命周期关键窗口期的人类暴露;2)定义动物模型中数据的作用模式和相关性;3)利用数学模型来做出合理的预测,作为:4)保护和恢复人类健康干预措施的基础。讨论集中在子宫内发育的关键窗口期。

总结

暴露评估、基础毒理学和某些类别的数学模型的开发并不是新的研究领域;然而,为了构思、评估和验证减轻或逆转环境暴露不良影响的有效干预措施,将这些因素明确地整合在一起是我们的新机会。这就是我们在转化毒理学中应该做的,以便我们拥有一系列改善人类健康的干预选择,包括最大限度地减少暴露和特定的预防/恢复/缓解治疗。

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