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Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation

机译:再谈狒狒辐照模型中全身体和部分身体暴露的生物标志物

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摘要

In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.
机译:在发生大规模伤亡辐射事件的情况下,需要区分全身辐射(TBI)和部分身体辐射(PBI),以将不堪重负的医疗资源集中于会发展为急性放射综合症(ARS)的个人,因此需要血液学支持(即主要是TBI受害者)。为了改善TBI与PBI个体的识别和医疗保健,可靠的暴露生物标志物可能非常有用。为了调查此问题,将成对的狒狒(n = 18)暴露在不同的TBI和PBI情况下,相当于5 Gy 60 Coγ射线(5 Gy TBI; 7.5 Gy左半身) /2.5右半身TBI; 5.55 Gy 90%PBI; 6.25 Gy 80%PBI; 10 Gy 50%PBI,15 Gy 30%PBI)或2.5 Gy(2.5 Gy TBI; 5 Gy 50%PBI)。在长达200天的几个时间点,在辐照前后评估了五十多个参数。偏最小二乘判别分析显示TBI与PBI情况(相当于5 Gy)有很好的区别。此外,将所有动物分为TBI(n = 6)和PBI(n = 12)两组,以进行逻辑回归和非参数统计检验进行比较。事实证明,在前驱阶段和明显疾病阶段,九种血浆生化标记和大多数血液学参数可区分TBI和PBI动物。最重要的生物标志物是早期的天冬氨酸转氨酶,肌酸激酶,乳酸脱氢酶,尿素,Flt3-配体,铁,C反应蛋白,绝对中性粒细胞计数和中性白细胞与淋巴细胞的比率,以及Flt3-配体,铁,血小板计数,血红蛋白,单核细胞计数,绝对嗜中性白血球计数和ARS期的嗜中性白细胞与淋巴细胞之比。这些结果表明异质性可以在2.5至5 Gy TBI的范围内区分。

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