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A study of calcium oxalate crystallization in kidney stone formation.

机译:草酸钙结晶在肾结石形成中的研究。

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This work was undertaken to gain a fundamental understanding of the physical and chemical mechanisms involved in the formation of kidney stones. Calcium oxalate is the major component of kidney stones and was chosen as the representative of stone minerals. Experiments were performed in a mixed-suspension, mixed-product-removal (MSMPR) crystallizer and in a flow chamber crystallizer.; Previous work has shown the significant influence of urinary macromolecules on calcium oxalate crystallization. Both inhibition and promotion of crystal growth and crystal aggregation by these biopolymers has been reported; however, crystal growth and crystal aggregation mechanisms were not isolated in these studies. In work conducted with the MSMPR crystallizer, the linear population density model has been used to describe nonlinear data; crystal growth rates were obtained but crystal aggregation was neglected. Crystal aggregation has been suspected as being important in stone formation.; In this work, experiments with the MSMPR crystallizer were conducted to characterize calcium oxalate crystallization. The entire MSMPR crystallization process was characterized by unsteady state, quasi-steady state, and steady state periods. At unsteady state, nucleation, crystal growth, and crystal aggregation all occurred in the system. In passing from the unsteady to the steady state, the crystallization process progressed with reduced nucleation and crystal aggregation. At steady state, only crystal growth was important. The unsteady state operation of the MSMPR crystallizer was of interest due to the presence of crystal aggregation; however, a clear understanding of the crystal aggregation mechanism depends upon knowing crystal growth kinetics.; An approach was developed to obtain crystal growth rate for the entire process, including unsteady and steady states, by identifying the shifts of particle size distributions along the x-axis with time. The growth rates obtained from this method correlated well with the results of the linear population density model and the experiments with a flow chamber crystallizer. With this method, a model urinary biopolymer, poly-L-glutamate (PGA), was identified as a growth rate inhibitor.; The flow chamber crystallizer experiments were conducted to investigate the effects of healthy and injured cultured epithelium (Maden Darby Canine Kidney (MDCK) cells) on the growth of single calcium oxalate crystals in the prescence of flow shear. Healthy MDCK cells were found to inhibit crystal nucleation. The crystal growth rate of calcium oxalate monohydrate (COM) decreased in the order of crystal growth on glass {dollar}>{dollar} MDCK cells treated with HCl {dollar}>{dollar} MDCK cells treated with papain {dollar}>{dollar} healthy MDCK cells. The biopolymer additive, heparin, inhibited COM crystal growth on healthy MDCK cells.
机译:进行这项工作是为了对肾结石形成所涉及的物理和化学机制有一个基本的了解。草酸钙是肾结石的主要成分,并被选为石材的代表。在混合悬浮,混合产物去除(MSMPR)结晶器和流动室结晶器中进行实验。先前的工作表明了尿大分子对草酸钙结晶的重大影响。这些生物聚合物都抑制和促进了晶体的生长和晶体的聚集。然而,在这些研究中并未分离出晶体生长和晶体聚集机制。在使用MSMPR结晶器进行的工作中,线性种群密度模型已用于描述非线性数据。获得了晶体生长速率,但是忽略了晶体聚集。怀疑晶体聚集在结石形成中很重要。在这项工作中,使用MSMPR结晶器进行了实验以表征草酸钙结晶。整个MSMPR结晶过程的特征在于非稳态,准稳态和稳态周期。在不稳定状态下,系统中会发生成核,晶体生长和晶体聚集。从不稳定状态转变为稳态状态时,结晶过程随着成核和晶体聚集的减少而进行。在稳态下,只有晶体生长很重要。由于存在晶体聚集,MSMPR结晶器的非稳态操作令人关注。然而,对晶体聚集机理的清晰理解取决于对晶体生长动力学的了解。通过确定沿x轴的粒度分布随时间的变化,开发了一种获得整个过程(包括非稳态和稳态)晶体生长速率的方法。通过这种方法获得的增长率与线性种群密度模型的结果以及流室结晶器的实验结果具有良好的相关性。用这种方法,模型尿生物聚合物,聚-L-谷氨酸(PGA)被鉴定为生长抑制剂。进行了流动室结晶器实验,以研究健康和受损的培养上皮(Maden Darby犬肾(MDCK)细胞)对单次草酸钙晶体在剪切流过时的生长的影响。发现健康的MDCK细胞抑制晶体成核。一水草酸钙(COM)的晶体生长速率按玻璃{美元}> {美元} HCl处理的MDCK细胞上的晶体生长顺序降低{美元}> {美元}木瓜蛋白酶处理的MDCK细胞{美元}> {美元}健康的MDCK细胞。生物聚合物添加剂肝素可抑制健康MDCK细胞上COM晶体的生长。

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