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国际放射防护委员会第67号出版物(ICRP 67)和美国国家辐射防护与测量委员会第156号报告(NCRP 156)生物动力学模型在非人灵长类动物241镅伤口数据中的应用。

Application of the ICRP 67 and NCRP 156 Biokinetic Models to 241 Am Wound Data from Nonhuman Primates.

作者信息

Alomairy Nada A, Brey Richard R, Guilmette Raymond A

出版信息

Health Phys. 2018 Mar;114(3):288-298. doi: 10.1097/HP.0000000000000775.

Abstract

Distribution, retention, and excretion of intramuscularly injected Am citrate have been investigated in cynomolgus and rhesus nonhuman primates (NHP). Bioassay and retention data, obtained from experiments done by Patricia Durbin and her colleagues at Lawrence Berkeley National Laboratory, were evaluated against the International Commission on Radiological Protection (ICRP 67) Am systemic model coupled with to the National Council on Radiation Protection and Measurement wound model (NCRP 156). The default transfer rates suggested in these models were used with the urine and feces excretion data to predict the intake as well as liver and skeleton tissue contents at the time of death. The default models adequately predict the animals' urine bioassay data, but the injected activities were overpredicted by as much 4.41 times and underpredicted by as much as 0.99 times. Poor prediction has been observed in all cases using fecal excretion. The retained activity in the liver and skeleton were investigated using the same approach. It appears that the models predict the amount of the activity retention in the skeleton more accurately than in the liver. The fraction of predicted to measured activity at the time of death in the skeleton was over 1.0 in most cases, and accurate predictions were obtained in seven cases. The predicted activity in skeleton for these cases ranged from 2.7 to 17% overestimated activity and from 9 to 14% underestimated activity. NHPs' urine data and organ retention were compared with data from previously modeled baboons and beagle dogs. About 6% of the injected activity in baboons and beagle dog was excreted in urine and approximately 0.1% in feces in the first 24 h. The results from NHP are not different from excreta analysis in these other species. Urinary excretion in the cynomolgus, rhesus, and baboon NHP is the dominant pathway of Am clearance; however, fecal excretion is considered dominant in beagle dogs. The comparison between NHPs and humans is difficult due to the differences in the number of activities translocated or deposited in the liver tissue and nonliver tissues (primarily skeleton), in addition to the physiological differences between the NHPs and humans.

摘要

已在食蟹猴和恒河猴这两种非人灵长类动物(NHP)中研究了肌肉注射柠檬酸镅的分布、滞留和排泄情况。对劳伦斯伯克利国家实验室的帕特里夏·德宾及其同事所做实验获得的生物测定和滞留数据,根据国际放射防护委员会(ICRP 67)的镅全身模型并结合美国国家辐射防护与测量委员会的伤口模型(NCRP 156)进行了评估。这些模型中建议的默认转移率与尿液和粪便排泄数据一起用于预测死亡时的摄入量以及肝脏和骨骼组织含量。默认模型能够充分预测动物的尿液生物测定数据,但注射活性的预测值高出实际值多达4.41倍,低出实际值多达0.99倍。在所有使用粪便排泄的情况下,预测效果都很差。采用相同方法研究了肝脏和骨骼中的滞留活性。看来这些模型对骨骼中活性滞留量的预测比对肝脏中活性滞留量的预测更准确。在大多数情况下,死亡时骨骼中预测活性与测量活性的比值超过1.0,有七个案例获得了准确的预测结果。这些案例中骨骼的预测活性高估活性范围为2.7%至17%,低估活性范围为9%至14%。将非人灵长类动物的尿液数据和器官滞留情况与先前建立模型的狒狒和比格犬的数据进行了比较。在最初24小时内,狒狒和比格犬中约6%的注射活性通过尿液排出,约0.1%通过粪便排出。非人灵长类动物的结果与这些其他物种的排泄物分析结果并无差异。食蟹猴、恒河猴和狒狒非人灵长类动物的尿液排泄是镅清除的主要途径;然而,在比格犬中,粪便排泄被认为是主要途径。由于非人灵长类动物和人类在肝脏组织和非肝脏组织(主要是骨骼)中转移或沉积的活性数量存在差异,以及非人灵长类动物和人类之间存在生理差异,因此很难对非人灵长类动物和人类进行比较。

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