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首页> 外文学位 >Compartmental modeling and dosimetry of in vivo metabolic studies of leucine and three secretory proteins in humans using radioactive tracers.
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Compartmental modeling and dosimetry of in vivo metabolic studies of leucine and three secretory proteins in humans using radioactive tracers.

机译：使用放射性示踪剂对人体中亮氨酸和三种分泌蛋白的体内代谢研究进行的区室建模和剂量测定。

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摘要

Physical and mathematical models provide a systematic means of looking at biological systems. Radioactive tracer kinetic studies open a unique window to study complex tracee systems such as protein metabolism in humans. This research deals with compartmental modeling of tracer kinetic data on leucine and apolipoprotein metabolism obtained using an endogenous tritiated leucine tracer administered as a bolus, and application of compartmental modeling techniques for dosimetric evaluation of metabolic studies of radioiodinated apolipoproteins. Dr. Waldo R. Fisher, Department of Medicine, was the coordinating research supervisor and the work was carried out in his laboratory.;A compartmental model for leucine kinetics in humans has been developed that emphasizes its recycling pathways which were examined over two weeks. This model builds on a previously published model of Cobelli et al, that analyzed leucine kinetic data up to only eight hours. The proposed model includes different routes for re-entry of leucine from protein breakdown into plasma accounting for proteins which turn over at different rates. This new model successfully incorporates published models of three secretory proteins: albumin, apoA-I, and VLDL apoB, in toto thus increasing its validity and utility. The published model of apoA-I, based on an exogenous radioiodinated tracer, was examined with data obtained using an endogenous leucine tracer using compartmental techniques. The analysis concludes that the major portion of apoA-I enters plasma by a fast pathway but the major fraction of apoA-I in plasma resides with a second slow pathway; further the study is suggestive of a precursor-product relationship between the two plasma apoA-I pools. The possible relevance of the latter suggestion to the aberrant kinetics of apoA-I in Tangier disease is discussed. The analysis of apoA-II data resulted in similar conclusions.;A methodology for evaluating the dosimetry of radioiodinated apolipoproteins by combining kinetic models of iodine and apolipoprotein metabolism has been developed. Residence times for source organs, whole body, thyroid, bladder, and red bone marrow obtained with this analysis, were used to calculate the cumulated activities and thus doses arising from these organs. The influence of the duration of the thyroid blocking period using stable iodine on the dose to the thyroid has been demonstrated.
机译：物理和数学模型提供了查看生物系统的系统方法。放射性示踪剂动力学研究为研究复杂的示踪剂系统（例如人类的蛋白质代谢）打开了一个独特的窗口。这项研究涉及使用内源性ti化亮氨酸示踪剂作为大剂量给药获得的有关亮氨酸和载脂蛋白代谢的示踪动力学数据的区室建模，以及区室建模技术在放射性碘化载脂蛋白代谢研究的剂量学评估中的应用。医学部的Waldo R. Fisher博士是协调研究主管，并且在他的实验室中进行了研究。已开发出人类亮氨酸动力学的区室模型，强调了其回收途径，并在两周内进行了研究。该模型建立在先前发布的Cobelli等人的模型的基础上，该模型仅分析了长达8小时的亮氨酸动力学数据。所提出的模型包括亮氨酸从蛋白质分解到血浆的再进入的不同途径，从而解释了以不同速率转换的蛋白质。这个新模型成功地结合了三种分泌蛋白的公开模型：白蛋白，apoA-I和VLDL apoB，从而提高了其有效性和实用性。使用隔室技术，使用内源性亮氨酸示踪剂获得的数据检查了基于外源放射性碘示踪剂的已发表的apoA-I模型。分析得出的结论是，apoA-I的主要部分通过快速途径进入血浆，而血浆中apoA-I的主要部分则通过第二条慢速途径进入。进一步的研究表明两个血浆apoA-I库之间存在前体-产物关系。讨论了后者的建议与丹吉尔病中apoA-I异常动力学的可能相关性。对apoA-II数据的分析得出了相似的结论。；已经开发了一种通过结合碘和载脂蛋白代谢动力学模型来评估放射性碘化载脂蛋白剂量学的方法。通过此分析获得的源器官，全身，甲状腺，膀胱和红骨髓的停留时间用于计算累积活动，从而计算这些器官产生的剂量。已经证明了使用稳定的碘对甲状腺阻断期的持续时间对甲状腺剂量的影响。

著录项

  • 作者

    Venkatakrishnan, Vaidehi.;

  • 作者单位

    University of Florida.;

  • 授予单位 University of Florida.;
  • 学科 Engineering Biomedical.;Health Sciences Radiology.;Physics Radiation.;Biophysics Medical.;Engineering Nuclear.
  • 学位 Ph.D.
  • 年度 1995
  • 页码 136 p.
  • 总页数 136
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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