FUNCTIONAL MODIFICATIONS OF SICKLE CELL ERYTHROCYTES

抗镰状病毒药物的一种潜在作用方式是 与血红蛋白分子的相互作用， 血红蛋白对氧的亲和力从而减少镰状化。锌已知 与分离的血红蛋白结合，导致氧气增加3-4倍， 亲和力 不幸的是，锌不能轻易通过红细胞膜。 然而，我们已经表明，螯合剂乙基麦芽酚，可以促进锌 通过红细胞的吸收，允许在一个细胞中的氧亲和力增加， 次给药结束依赖的方式。我们已经研究了孵化的影响， 增加锌络合物浓度对变形性的影响， 镰状红细胞的血液学指标。变形能力不是 在低浓度下受影响，但MCHC大大降低。下降 MCHC值在影响HbS动力学方面具有明显优势 聚合法这项工作的数据正在汇编中，以供出版。 2)作为对镰状细胞变异性的长期兴趣的一部分， 疾病在人群中的表达，我们目前正在合作 与G博士Rodgers和NIDDK的其他人在使用基于计算机的 分析了140例非霍奇金淋巴瘤患者的生化、血液学和临床资料， 非洲镰状细胞病患者已知经历一种较温和的贫血形式。 预测聚合物分数作为氧饱和度的函数， 将建立与疾病严重程度的关系，并与类似的 其他更严重的镰状细胞综合征的参数。

One potential mode of action of an antisickling drug would be an interaction with the hemoglobin molecule that would increase the hemoglobin's affinity for oxygen thereby reducing sickling. Zinc is known to bind to isolated hemoglobin and causes a 3-4 fold increase in oxygen affinity. Unfortunately, zinc cannot easily pass through the red blood cell membrane. However, we have shown that the chelator, ethyl maltol, can facilitate zinc uptake by red blood cells allowing an increase in the oxygen affinity in a dose. dependant fashion. We have examined the effects of incubation with increasing concentrations of zinc complex on deformability and hematological indices of sickle erythrocytes. The deformability was not affected at low concentrations yet MCHC was greatly decreased. A drop in the MCHC values is a definite advantage in influencing the kinetics of HbS polymerization. Data from this work are being compiled for publication. 2) As part of a long standing interest in the variability in sickle cell disease expression in human populations, we are currently collaborating with Dr. G. Rodgers and others at NIDDK in employing a computer based analysis of biochemical, hematological, and clinical data on some 140 non African sickle cell patients known to experience a milder form of anemia. Prediction of polymer fraction as a function of oxygen saturation in relation to disease severity will be established and compared to similar parameters of other, more severe sickle cell syndromes.