PHYSICO-CHEMICAL ASPECTS OF RENAL TRANSPORT PROCESSES
肾脏运输过程的物理化学方面
基本信息
- 批准号:2015993
- 负责人:
- 金额:$ 16.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1977
- 资助国家:美国
- 起止时间:1977-08-01 至 1999-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The normal glomerular capillary wall is extremely permeable to water, and
yet very effective at preventing the loss of plasma proteins into the
glomerular ultrafiltrate. In the principal forms of kidney disease both of
these aspects of glomerular function tend to be impaired: there is a
reduced capacity for filtration of water, accompanied by less ability to
selectively retain plasma proteins. Clearance studies in experimental
animals and humans using various exogenous polymers have established that
the selectivity of the glomerular barrier to macromolecules is based on
both molecular size and molecular charge, but the biophysical basis for
normal or impaired selectivity remains poorly understood. Specifically,
the mathematical models currently available to interpret such data offer
little insight into how structural changes in the glomerular-capillary
wall might affect its performance as an ultrafiltration membrane. The
overall objective of the proposed research is to develop new theoretical
models which will relate the size- and charge-selective properties of the
glomerular barrier to the physical characteristics of particular
structures within the capillary wall. One specific aim is to synthesize
and characterize a new anionic test macromolecule, Ficoll sulfate, for use
as a probe of glomerular charge-selectivity. A second aim is to study
convection and diffusion of macromolecules of varying size and charge in
well-characterized synthetic gels, which will be used as experimental
models for transport in the glomerular basement membrane. The physical
relationships established in those studies will assist in the achievement
of a third specific aim, which is to analyze filtration and diffusion data
obtained with neutral Ficoll and Ficoll sulfate in isolated rat glomerular
basement membrane. The synthetic gels and the basement membrane will both
be modeled as media where transport is through fluid-filled interstices
among a disordered array of fibers, and the restrictions to molecules of
varying size and charge will be interpreted in terms of physical
parameters such as fiber radius, fiber charge, and average interfiber
spacing. As the final major aim, a theoretical model for macromolecule
transport across the intact glomerular capillary wall will be developed,
based on a repeating structural unit consisting of a single epithelial
filtration slit and corresponding areas of basement membrane and
fenestrated endothelium. This model will be used to elucidate the
contributions of the various individual structures to glomerular
permeability properties observed in health and disease.
正常的肾小球毛细血管壁对水具有极强的渗透性,
但非常有效地防止血浆蛋白流失到
肾小球超滤液在肾脏疾病的主要形式中,
肾小球功能的这些方面往往受损:
过滤水的能力降低,伴随着
选择性地保留血浆蛋白。实验中的清除研究
使用各种外源聚合物的动物和人类已经证实,
肾小球屏障对大分子的选择性是基于
分子大小和分子电荷,但生物物理基础
正常或受损的选择性仍然知之甚少。具体地说,
目前可用于解释这些数据的数学模型提供了
对肾小球毛细血管的结构变化
壁可能会影响其作为超滤膜的性能。的
研究的总体目标是发展新的理论
模型,这将涉及的大小和电荷选择性的性质,
肾小球屏障的物理特性,特别是
毛细血管壁内的结构。一个具体的目标是合成
并表征了一种新的阴离子测试大分子,Ficoll硫酸盐,
作为肾小球电荷选择性的探针。第二个目标是研究
不同大小和电荷的大分子的对流和扩散
良好表征的合成凝胶,将用作实验
肾小球基底膜转运模型。物理
在这些研究中建立的关系将有助于实现
第三个具体目标是分析过滤和扩散数据,
用中性Ficoll和Ficoll硫酸盐在离体大鼠肾小球中获得
基底膜合成凝胶和基底膜
被建模为介质,其中传输是通过充满流体的间隙
在无序排列的纤维中,
不同的大小和电荷将被解释为物理上的
参数,如纤维半径,纤维电荷,和平均纤维间
间距。作为最终的主要目标,
将产生穿过完整肾小球毛细血管壁的转运,
基于由单个上皮细胞组成的重复结构单元
滤过狭缝和相应的基底膜区域,
有孔内皮该模型将用于阐明
各种个体结构对肾小球的贡献
在健康和疾病中观察到的渗透性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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William M Deen其他文献
William M Deen的其他文献
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{{ truncateString('William M Deen', 18)}}的其他基金
Reaction and Diffusion of NO in Biological Systems
NO 在生物系统中的反应和扩散
- 批准号:
6990319 - 财政年份:2004
- 资助金额:
$ 16.07万 - 项目类别:
REACTION AND DIFFUSION OF NITRIC OXIDE IN BIOLOGICAL SYSTEMS
一氧化氮在生物系统中的反应和扩散
- 批准号:
6563790 - 财政年份:2002
- 资助金额:
$ 16.07万 - 项目类别:
REACTION AND DIFFUSION OF NITRIC OXIDE IN BIOLOGICAL SYSTEMS
一氧化氮在生物系统中的反应和扩散
- 批准号:
6300201 - 财政年份:2000
- 资助金额:
$ 16.07万 - 项目类别:
REACTION AND DIFFUSION OF NITRIC OXIDE IN BIOLOGICAL SYSTEMS
一氧化氮在生物系统中的反应和扩散
- 批准号:
6102034 - 财政年份:1999
- 资助金额:
$ 16.07万 - 项目类别:
MUTATIONAL SPECTRA INDUCED BY NITRIC OXIDE, PEROXYNITRITE AND REACTIVE OXIDANTS
一氧化氮、过氧亚硝酸盐和活性氧化剂诱导的突变谱
- 批准号:
6269095 - 财政年份:1998
- 资助金额:
$ 16.07万 - 项目类别:
MUTATIONAL SPECTRA INDUCED BY NITRIC OXIDE, PEROXYNITRITE AND REACTIVE OXIDANTS
一氧化氮、过氧亚硝酸盐和活性氧化剂诱导的突变谱
- 批准号:
6236569 - 财政年份:1997
- 资助金额:
$ 16.07万 - 项目类别:
GLOMERULAR HYPERTENSION AND SIEVING OF MACROMOLECULES
肾小球高血压和大分子筛选
- 批准号:
2141848 - 财政年份:1991
- 资助金额:
$ 16.07万 - 项目类别:
GLOMERULAR HYPERTENSION AND SIEVING OF MACROMOLECULES
肾小球高血压和大分子筛选
- 批准号:
3242454 - 财政年份:1991
- 资助金额:
$ 16.07万 - 项目类别:
GLOMERULAR HYPERTENSION AND SIEVING OF MACROMOLECULES
肾小球高血压和大分子筛选
- 批准号:
3242453 - 财政年份:1991
- 资助金额:
$ 16.07万 - 项目类别:
PHYSICO-CHEMICAL ASPECTS OF RENAL TRANSPORT PROCESSES
肾脏运输过程的物理化学方面
- 批准号:
3483347 - 财政年份:1977
- 资助金额:
$ 16.07万 - 项目类别:
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