Evaluation and modification of a physiologically based model of lead kinetics using data from a sequential isotope study in cynomolgus monkeys.
Evaluation and modification of a physiologically based model of lead kinetics using data from a sequential isotope study in cynomolgus monkeys.
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使用食蟹猴连续同位素研究的数据评估和修改基于生理的铅动力学模型。
DOI：
10.1006/taap.1997.8328
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发表时间：
1998
影响因子：
3.8
通讯作者：
Baccanale,CL
中科院分区：
文献类型：
--
作者：
O'Flaherty,EJ;Inskip,MJ;Franklin,CA;Durbin,PW;Manton,WI;Baccanale,CL
对两只 11 岁雌性食蟹猴 (Macaca fasciculis) 的内源性（主要是骨骼）和外源性铅进行了差异标记，以确定这两种来源对血铅的贡献。从 10 个月大直至研究开始，这些猴子均以约 1300 μg Pb/kg 体重/天的剂量服用常见的铅同位素“混合物”。在第 0 天，普通铅依次被人工富集 204 Pb、206 Pb 和 207 Pb 的混合物取代，持续 50 至 281 天。总铅摄入率保持恒定，除了在向其中一只猴子施用富含207 Pb的混合物期间，总铅摄入率降低至650μg/kg/天。每隔一定时间对血液和骨骼进行采样，并分析每种同位素混合物的含量。基于生理学的人类铅动力学模型被缩放到食蟹猴并拟合数据，以测试模型结构的正确性并协助解释研究结果。改变吸收分数以实现缩放模型与每只猴子的血液和骨浓度数据的最佳视觉拟合。该模型未能重现每次同位素混合物交换后观察到的血液中同位素浓度急剧下降的情况。因此，使用成年食蟹猴组织形态计量学研究对小梁骨和皮质骨周转率的估计，对其进行了修改，包括快速周转的小梁骨室和慢周转的皮质骨室。修改后的模型很好地拟合了大多数骨和血液浓度组。暴露 11 年后，当血铅浓度超过 50 μg/dl 时，约 17% 的血铅源自骨骼。根据模型估计，在第 0 天受控普通铅暴露终止之前，普通铅从骨骼的返回率为 28 μg/天。基于比例人体模型成功拟合这些数据以及骨骼和血铅浓度的绝对值和相对值，食蟹猴中的铅代谢似乎与人类铅代谢相似。
Endogenous (predominantly bone) and exogenous lead were differentially labeled in two 11-year-old female cynomolgus monkeys (Macaca fascicularis) to establish the contributions of the two sources to blood lead. The monkeys had been administered a common lead isotope “mix” at the rate of about 1300 μg Pb/kg body wt/day from age 10 months until the start of the study. On day 0, common lead was replaced in sequence by mixes artificially enriched in204Pb,206Pb, and207Pb, given for periods of from 50 to 281 days. Total lead ingestion rate was held constant except during administration of the207Pb-enriched mix to one of the monkeys, when it was reduced to 650 μg/kg/day. Blood and bone were sampled at intervals and analyzed for their content of each of the isotope mixes. A physiologically based model of human lead kinetics was scaled to the cynomolgus monkey and fit to the data to test the correctness of the model structure and to assist with interpretation of study results. Fractional absorption was varied to achieve the best visual fits of the scaled model to blood and bone concentration data for each monkey. The model failed to reproduce the sharp drop in isotope concentrations in blood observed after each exchange of isotope mix. Consequently, it was revised to include a rapid-turnover trabecular bone compartment and a slow-turnover cortical bone compartment, using estimates of trabecular and cortical bone turnover rates from histomorphometric studies in adult cynomolgus monkeys. The revised model fit most of the sets of bone and blood concentrations well. About 17% of the blood lead originated from bone after 11 years of exposure, at blood lead concentrations in excess of 50 μg/dl. The rate of return of common lead from bone, as estimated from the model, was 28 μg/day just before termination of controlled common lead exposure on day 0. Based on the success of the scaled human model in fitting these data and on the absolute and relative values of bone and blood lead concentrations, the metabolism of lead in the cynomolgus monkey appears to be similar to human lead metabolism.
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影响因子：
3.5
作者：
A. Beddoe
通讯作者：
A. Beddoe
DOI：
--
发表时间：
1995-06
期刊：
The Journal of laboratory and clinical medicine
影响因子：
--
作者：
B. Gulson;K. Mahaffey;K. Mizon;M. Korsch;M. Cameron;G. Vimpani
通讯作者：
B. Gulson;K. Mahaffey;K. Mizon;M. Korsch;M. Cameron;G. Vimpani
雄性大鼠股骨中轴骨膜和皮质骨内骨形成和吸收的定量测量。
影响因子：
4.1
作者：
W. Sontag
通讯作者：
W. Sontag
基于生理学的寻骨元素模型。
影响因子：
3.8
作者：
O'Flaherty,EJ
通讯作者：
O'Flaherty,EJ
通过基于生理学的铅动力学模型评估铅的生物利用度数据。
DOI：
10.1093/toxsci/29.1.63
发表时间：
1996
期刊：
Fundamental and applied toxicology : official journal of the Society of Toxicology
影响因子：
--
作者：
J. Polák;E. O'FLAHERTY;G. B. Freeman;J. Johnson;S. Liao;P. D. Bergstrom
通讯作者：
P. D. Bergstrom