Exploring calcium oxalate crystallization: a constant composition approach.

Exploring calcium oxalate crystallization: a constant composition approach.
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DOI:
10.1007/s00240-015-0781-5
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发表时间:
2015-10
期刊:
影响因子:
3.1
通讯作者:
Wesson JA
Wesson JA
中科院分区:
医学2区
文献类型:
--
作者:
Kolbach-Mandel AM;Kleinman JG;Wesson JA

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一水草酸钙(COM)结晶中的晶体生长速率已被广泛研究,因为COM晶体是大多数肾结石的主要成分。恒定组成的方法是有用的研究生长速率,但不能区分并发成核和聚集事件。一个恒定的组合物的方法加上粒度测定,解决了这一缺陷,以前发表的磷酸钙系统,这种方法被扩展到COM结晶在本报告中。种子恒定组合物实验结合粒度测定和单独的近平衡聚集实验,以分离COM晶体形成中的生长速率、成核和聚集的影响,并测试与结石形成相关的各种抑制剂的影响。在没有抑制剂存在下,表观COM生长速率在很大程度上受二次成核在低晶种添加,但生长相关的聚集在较高的晶种密度增加。在小分子抑制剂中,柠檬酸盐表现出生长速率抑制,但增强生长相关的聚集,而镁不影响COM结晶。聚阴离子(聚天冬氨酸,聚谷氨酸,或骨桥蛋白)表现出较强的生长速率抑制,但在成核和聚集观察到很大的差异。聚阳离子(聚精氨酸)没有影响COM晶体的生长或聚集。聚阴离子和聚阳离子的混合物产生了一组复杂的生长速率,成核和聚集行为。这些实验证明了将粒度测定与恒定组合物实验相结合的能力,以充分表征COM结晶并获得对理解肾结石形成至关重要的抑制剂性质的详细知识。
Crystal growth rates have been extensively studied in calcium oxalate monohydrate (COM) crystallization, because COM crystals are the principal component in most kidney stones. Constant composition methods are useful for studying growth rates, but fail to differentiate concurrent nucleation and aggregation events. A constant composition method coupled with particle size determinations that addresses this deficiency was previously published for a calcium phosphate system, and this method was extended to COM crystallization in this report. A seeded constant composition experiment was combined with particle size determination and a separate near-equilibrium aggregation experiment to separate effects of growth rate, nucleation, and aggregation in COM crystal formation and to test the effects of various inhibitors relevant to stone formation. With no inhibitors present, apparent COM growth rates were heavily influenced by secondary nucleation at low seed crystal additions, but growth-related aggregation increased at higher seed crystal densities. Among small molecule inhibitors, citrate demonstrated growth rate inhibition but enhanced growth-related aggregation, while magnesium did not affect COM crystallization. Polyanions (polyaspartate, polyglutamate, or osteopontin) showed strong growth rate inhibition, but large differences in nucleation and aggregation were observed. Polycations (polyarginine) did not affect COM crystal growth or aggregation. Mixtures of polyanions and polycations produced a complicated set of growth rate, nucleation, and aggregation behaviors. These experiments demonstrated the power of combining particle size determinations with constant composition experiments to fully characterize COM crystallization and to obtain detailed knowledge of inhibitor properties that will be critical to understanding kidney stone formation.