Making bloodwork work: the impact of sample collection, processing, and storage on plasma glutathione measurement, and implications for translation.

IF 5.8 1区 医学 Q1 PSYCHIATRY
Kendall M Coden, Duyen K K Nguyen, Roberta Moorhead, Beatriz E Stix-Brunell, Joanna N Baker, Karen J Parker, Joseph P Garner
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引用次数: 0

Abstract

Psychiatry has traditionally focused on the study of neurons and neurotransmitter physiology in the pathophysiology and treatment of psychiatric disorders. A growing literature highlights REDOX imbalance (a state in which demand for antioxidants surpasses their bioavailability) as a common pathophysiology for a diverse array of brain conditions (e.g., trichotillomania, schizophrenia, autism, Parkinson's disease). REDOX imbalance is typically measured via plasma glutathione, as glutathione is critical to the adaptive antioxidant response in the brain. Accordingly, glutathione, its precursors, and/or metabolites serve as biomarkers of disease risk, therapeutic targets, and measures of treatment response. However, as with any emerging field, there are currently several different methods for collection, processing, storage, and calculation of summary measures of plasma glutathione metabolism, within and between preclinical and clinical research. The lack of evidence-based best-practice methodology hampers reproducibility (preclinical or clinical), and translation (between preclinical and clinical work). To address this methodological need, here we used a repeated measures within-subject design to investigate how sample preparation (type of anticoagulant used during blood collection, deproteinization status, and storage temperature) affects plasma glutathione levels. Accordingly, we collected whole blood from mice (N = 13), and then, using a commercially available kit, quantified glutathione in plasma stored in four different ways. Presuming that these preparation conditions and post-processing calculations are unimportant, we would expect to see no difference in glutathione levels and summary measures from the same sample. However, we found each of these variables to significantly alter quantified glutathione levels. Accordingly, we propose a vital, gold-standard methodology for both sample collection, processing, and storage of plasma used for glutathione quantification and for summary calculations of glutathione that can be used preclinically and clinically, thus yielding more streamlined translation.

让血液工作发挥作用:样本采集、处理和储存对血浆谷胱甘肽测量的影响以及转化的意义。
精神病学历来侧重于研究神经元和神经递质在精神疾病的病理生理学和治疗中的生理作用。越来越多的文献强调 REDOX 失衡(一种对抗氧化剂的需求超过其生物利用率的状态)是各种脑部疾病(如毛滴虫症、精神分裂症、自闭症、帕金森病)的常见病理生理学。由于谷胱甘肽对大脑的适应性抗氧化反应至关重要,因此通常通过血浆谷胱甘肽来测量氧化还原失衡。因此,谷胱甘肽、其前体和/或代谢物可作为疾病风险的生物标志物、治疗目标和治疗反应的测量指标。然而,与任何新兴领域一样,目前在临床前研究和临床研究内部以及之间,有几种不同的方法用于收集、处理、储存和计算血浆谷胱甘肽代谢的简要测量值。缺乏以证据为基础的最佳实践方法阻碍了可重复性(临床前或临床)和转化(临床前和临床工作之间)。为了满足这一方法学需求,我们在此采用受试者内重复测量设计来研究样本制备(采血时使用的抗凝剂类型、去蛋白状态和储存温度)如何影响血浆谷胱甘肽水平。因此,我们采集了小鼠(N = 13)的全血,然后使用市售试剂盒对以四种不同方式储存的血浆中的谷胱甘肽进行了定量。假设这些制备条件和后处理计算并不重要,我们预计同一样本的谷胱甘肽水平和摘要测量结果不会有差异。然而,我们发现这些变量都会显著改变谷胱甘肽的量化水平。因此,我们为用于谷胱甘肽定量的血浆样本收集、处理和储存以及谷胱甘肽的汇总计算提出了一种重要的黄金标准方法,该方法可用于临床前和临床,从而实现更简便的转化。
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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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