Kanabrocki E L, Sothern R B, Ryan M D, Kahn S, Augustine G, Johnson C, Foley S, Gathing A, Eastman G, Friedman N, Nemchausky B A, Kaplan E
Nuclear Medicine, Edward Hines Jr., Veterans Administration Hospital, Hines, IL 60141, USA.
Clin Ter. 2008 Sep-Oct;159(5):329-46.
To monitor the around-the-clock distribution of serum and urine concentrations of calcium, magnesium and eight trace elements and of those same elements in urine after their dialysis, and to statistically describe their circadian characteristics by chronobiological procedures.
Serum and urine samples were collected every 3h over a single 24h period from eleven clinically-healthy male subjects, 41-60 years of age, and were analyzed for calcium (Ca), magnesium (Mg), iron (Fe), copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), cobalt (Co), chromium (Cr), and nickel (Ni). Urines were also sequentially dialyzed against ammonium-barbituric acid buffer at pH 7.35+/-0.02 using a 12.000-14.000 molecular weight exclusion sieve and then reanalyzed for the same elements. Urine concentrations were adjusted by urine volume to reflect a 3h excretion rate. Time-series were analyzed for circadian time-effect by ANOVA and for rhythm characteristics by the single cosinor fitting procedure.
The dialysis effectively removed 90% of total solids, 97% of urea, 92% creatinine, 72% uric acid, and essentially all of glucose. It also removed 99% of potassium (K), 96% of sodium (Na), 65% of Ca and P, 55% of Mg, 41% of Zn and 88% of Ni. A significant or borderline-significant 24h rhythm in serum was detected for Ca, Mg, Fe, Cu, Zn, Cd and Cr; in untreated urine for Ca, Fe, Cu, Zn, Ni, creatinine and volume; and in dialyzed urine for Ca, Fe, Cu, Zn, Pb, Cr, Cd and Ni. A 12h component was significant or borderline-significant in serum for Mg, Fe, Zn, and Cd; in untreated urine for volume, creatinine, Ca, Mg, Cu, and Ni; and in dialyzed urine for Ca, Mg, Fe, Cu, Zn, and Cr. In general, values in serum were lowest near the onset of sleep and highest in the first half of the day (between 02:28 and 13:56 h), while highest values in untreated or dialyzed urine were found several hours later in the day and at night.
Significant circadian variations were found in levels of nearly every element that was measured in blood and urine of 11 healthy men, but with highest and lowest levels occurring at different times. This suggests not only that urine concentrations need to be adjusted for collection time interval and urine volume, but that different biological limits at different times of the 24h day should be applied for serum and urinary monitoring of trace elements. We also found that the non-dialyzable segments of these elements in urine represent metallo-moieties composed of proteinacious matter greater than 12,000-14,000 Daltons. Further studies would be of interest to reveal time specificity for metabolic functions associated with any of these trace elements.
监测钙、镁及八种微量元素在血清和尿液中的昼夜分布情况，以及这些元素在透析后的尿液中的分布情况，并通过时间生物学方法对其昼夜特征进行统计学描述。
在一个24小时的时间段内，每隔3小时从11名年龄在41至60岁之间的临床健康男性受试者身上采集血清和尿液样本，并对钙（Ca）、镁（Mg）、铁（Fe）、铜（Cu）、锌（Zn）、铅（Pb）、镉（Cd）、钴（Co）、铬（Cr）和镍（Ni）进行分析。尿液还使用分子量为12000至14000的排阻筛，依次用pH值为7.35±0.02的巴比妥酸铵缓冲液进行透析，然后对相同元素进行重新分析。尿液浓度通过尿量进行调整，以反映3小时的排泄率。通过方差分析对时间序列进行昼夜时间效应分析，并通过单余弦拟合程序分析节律特征。
透析有效去除了90%的总固体、97%的尿素、92%的肌酐、72%的尿酸以及几乎所有的葡萄糖。它还去除了99%的钾（K）、96%的钠（Na）、65%的钙和磷、55%的镁、41%的锌和88%的镍。在血清中，钙、镁、铁、铜、锌、镉和铬检测到显著或临界显著的24小时节律；在未处理的尿液中，钙、铁、铜、锌、镍、肌酐和尿量检测到节律；在透析后的尿液中，钙、铁、铜、锌、铅、铬、镉和镍检测到节律。在血清中，镁、铁、锌和镉的12小时成分显著或临界显著；在未处理的尿液中，尿量、肌酐、钙、镁、铜和镍的12小时成分显著或临界显著；在透析后的尿液中，钙、镁、铁、铜、锌和铬的12小时成分显著或临界显著。一般来说，血清中的值在睡眠开始时最低，在一天的前半段（02:28至13:56小时之间）最高，而未处理或透析后的尿液中的最高值在一天中的数小时后以及夜间出现。
在11名健康男性的血液和尿液中，几乎每种测量元素的水平都存在显著的昼夜变化，但最高和最低水平出现在不同时间。这不仅表明尿液浓度需要根据采集时间间隔和尿量进行调整，而且在24小时的不同时间应应用不同的生物学限值进行微量元素的血清和尿液监测。我们还发现，尿液中这些元素的不可透析部分代表了由大于12000至14000道尔顿的蛋白质物质组成的金属部分。进一步的研究将有助于揭示与这些微量元素中的任何一种相关的代谢功能的时间特异性。
