Serum and tissue trace elements in patients with breast cancer in Taiwan

The objective of this study was to compare levels of four elements (zinc, copper, selenium, and iron) in the serum and tissue of 68 breast tumor patients (benign and malignant), from a teaching hospital in central Taiwan. Samples of normal tissue (5 cm away from tumor) were also taken from patients with malignant tumors. Only serum was taken from the 25 healthy persons in the control group. Results showed that Zn, Cu, Se, Fe, Cu/Zn, Cu/Se, and Cu/Fe were present in different amounts in the serum of each of the three groups. Zn and Se levels were lower in the serum of the two tumor groups compared to the control group. In tissue samples, Zn, Cu, Se, and Fe concentrations were different in each of the three groups. The malignant tissue had the highest levels of all four elements. In advanced-stage malignant tumors, levels of Cu and the ratios of Cu/Fe and Cu/Zn (in both serum and tissue) were highest. The ratios of serum Cu/Zn, Cu/Fe, and Cu/Se were also higher in malignant patients. The cutoff value of serum Cu/Zn was 1.2 (sensitivity and specificity were both 100%). The Cu/Zn ratio was highest in the advanced stages of cancer and was a better diagnostic tool for breast cancer than Cu/Se and Cu/Fe. The authors suggest that change of trace elements in serum and tissue might be useful and significant as biomarkers involving the initial plastic process.     

利用黑腹果蝇（Drosophila melanogaster）研究微量金属元素代谢

微量金属参与了生物体许多化学反应过程,同时也可作为蛋白质的辅基或辅因子起作用,对机体生长发育以及正常生物功能的维持具有重要作用;微量金属元素的代谢失衡与生物体许多疾病密切相关,如威尔森氏病、门克斯病、铁色素沉积、肠变性皮炎以及一些神经退行性疾病。黑腹果蝇（Drosophila melanogaster）是遗传背景清楚、生活周期短、操作方便的模式生物,利用果蝇研究金属离子代谢以及金属离子代谢与疾病的联系具有独特的优势,近年来,随着果蝇基因组测序的完成以及许多转基因果蝇株的建立,果蝇也越来越多的用于金属离子代谢的研究。介绍了近年来果蝇在金属离子代谢研究领域的进展,以及其与神经退行性疾病关系研究上的一些应用。     

Cadmium-induced alterations in ocular trace elements

The present report demonstrates, for the first time, that feeding rats 50 ppm cadmium for just 7 wk results in detectable levels of cadmium in the eye of rats. Furthermore, these ocular cadmium concentrations affect significant alterations in the levels of the essential trace elements selenium, calcium iron, and copper in the eye. Rats were fed a low-selenium (<0.02 ppm selenium), high-copper basal diet (50 ppm copper) supplemented with 0, 0.1, and 0.5 ppm selenium. The animals were either untreated or treated with 50 ppm cadmium admixed with their feed. Cadmium treatment resulted in significant reductions (up to 50%) in ocular selenium. Furthermore, rats fed the basal diet and given 100 ppm cadmium via their feed for 6 wk exhibited a 69% reduction in the activity of the selenoenzyme, glutathione peroxidase, in the eye. Cadmium treatment also resulted in reductions of up to 50% in ocular calcium, irrespective of dietary selenium supplementation. Iron levels were increased by 30% in rats fed the low-selenium diet and decreased by as much as 40% in rats fed the selenium-supplemented diets, compared to animals fed identical levels of selenium without cadmium. Ocular copper levels were significantly increased only in rats fed the low-selenium diet and treated with cadmium. Ocular zinc levels were not significantly affected by dietary cadmium or selenium.     

The concentration of twelve elements in the anterior pituitary from human subjects and rats as measured by particle induced X-ray emission (PIXE)

The concentration of twelve elements—potassium, calcium, manganese, iron, cobalt, nickel, copper, zinc, arsenic, selenium, bromine, and rubidium—in anterior pituitaries from human subjects and rats was measured using Particle Induced X-ray Emission (PIXE). The human material included anterior pituitaries from 37 normal human subjects, 27 males and 10 females, all of whom died from traumatic lesions. Excluded from the investigations were persons with alcohol abuse, regular use of drugs, and babies younger than 1 year. For selenium, zinc, bromine, and to some extent copper, there was good correlation between the amounts found in anterior pituitaries from rats and human subjects. A significant difference between male and female rat pituitaries was observed for copper, iron, and rubidium, whereas for humans significant difference was only observed for manganese. Anterior pituitaries from human females contained generally more zinc than male glands, but the concentration of zinc in young males was higher than in females. The present study also indicates age related differences in the copper content in anterior pituitaries from human subjects, since pituitaries from humans between 15–45 years contained 25% more copper than those from younger or older persons. The opposite pattern was observed in males. For such elements as Cu, Fe, Mn, and Se, the content in the anterior pituitary from human subjects was 1.6–2 times that stated for other endocrine organs.     

Changed serum trace element profile in Down's syndrome

Being cofactors of important antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), which are significantly modified in Down's syndrome (trisomy 21), serum levels of microtrace elements zinc, copper, and selenium and of macroelement magnesium are reported in 16 subjects with Down's syndrome (DS) and their respective well age- and sex-matched controls. Serum zinc and selenium levels were significantly lowered in DS subjects, whereas copper levels were elevated. Consequently, a marked increase (40%) of the copper/zinc ratio in DS persons was observed. There were no differences in serum levels of magnesium between DS and control subjects.     

模式生物斑马鱼在微量元素代谢研究中的应用

微量元素如铁、锌、铜等对维持生物体代谢和健康至关重要,其含量失衡会造成代谢异常甚至死亡,因此生物体存在复杂机制维持这些微量元素的稳态代谢平衡（homeostasis）。近年来国际上一些实验室尝试用模式脊椎生物斑马鱼来开展该领域的研究,展示出斑马鱼的特有优势。特别是大规模正向遗传学筛选的成功开展,一系列微量元素代谢异常的突变体（如：weissherbst、chardonnay、chianti、shiraz、gavi、calamity和catastrophe）相继发现,为研究离子代谢调控机制和相关疾病的发病机理,提供了整体动态的活体模型。铁代谢相关基因加,2J和grx5都己在斑马鱼中成功定位克隆,斑马鱼铜载体基因atp7a突变体calamity的深入研究,进一步阐明了Menkes病的发病机理。利用斑马鱼的优势,结合小鼠模型和人群来研究微量元素的体内稳态代谢平衡将是微量元素代谢机制研究的新方向。     

Changes in serum selenium, copper, zinc levels and Cu/Zn ratio in patients with pulmonary tuberculosis during therapy

The effectiveness and success of antituberculosis therapy is mainly measured by its ability to identify the organism in the sputum. In certain cases, available tuberculosis tests are not satisfactory and do not provide enough information on the effectiveness of antituberculosis therapy. Copper (Cu), zinc (Zn), and selenium (Se) are the essential elements that play a crucial role in the immune system. The serum levels of these elements vary in many diseases including tuberculosis. In this study, we investigate whether the serum levels of Cu, Zn, and Se change during antituberculosis therapy. We have included 22 pulmonary tuberculosis cases that were newly diagnosed with positive sputum and 18 healthy subjects. At the beginning and 2 mo after therapy, serum levels of Cu, Zn, and Se were measured by atomic absorption spectrometry. Despite Se and Cu levels not being affected during the treatment, we found that there was a significant increase in the levels of Zn and a decrease in the Cu/Zn ratio. Serum Zn levels and the Cu/Zn ratio could be used as a valuable laboratory tool for the clinicians to assess response to therapy or effectiveness of the ongoing antituberculosis therapy.     

Alterations in plasma essential trace elements selenium, manganese, zinc, copper, and iron concentrations and the possible role of these elements on oxidative status in patients with childhood asthma

The aim of the present study is to evaluate the status of plasma essential trace element selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations and the effect of these elements on oxidative status in patients with childhood asthma. Plasma Se, Mn, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry (AAS) and Fe concentrations, malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined by the colorimetric method. The plasma MDA/TAC ratio was calculated as an index of oxidative status. Plasma albumin levels were measured to determine nutritional status. Plasma Fe concentrations, MDA levels and the MDA/TAC ratio were significantly higher (p<0.001, p<0.001, and p<0.01, respectively) and Se and Mn concentrations and TAC were lower (p<0.01, p<0.05, and p<0.01, respectively) in patients when compared to the healthy subjects. Plasma Zn, Cu, and albumin levels were not found to be significantly different in patients and controls (p>0.05). There were positive relationships between plasma MDA and Fe (r=0.545, p<0.001) and TAC and Se (r=0.485, p<0.021), and a negative correlation between TAC and MDA values (r= −0.337, p<0.031) in patients with childhood asthma. However, there was no correlation between these trace elements and albumin content in patient groups. These observations suggest that increased Fe and decreased Se concentrations in patients with childhood asthma may be responsible for the oxidant/antioxidant imbalance.     

Significance of serum trace element status in patients with rheumatic heart disease

It is known that certain trace elements can affect various heart diseases. In this study, we aimed to evaluate the changes in concentrations of certain serum trace elements in patients with chronic rheumatic heart disease (RHD). Serum analysis of selenium (Se), zinc (Zn), and copper (Cu) trace elements was assayed by atomic absorption spectrophotometry. RHD patients had significantly lower serum concentrations of Se and Zn than control subjects (p<0.05 and p<0.001, respectively). However, the serum Cu concentration was significantly higher in RHD patients than in controls (1.93±0.59 μg/L vs 1.06±0.29 μg/L; p<0.001). Similarly, the Cu/Zn ratio in RHD patients was higher than in control subjects (4.70±0.92 vs 1.68±0.45; p<0.001). Additionally, no significant correlation was found among these trace element concentrations and the functional capacity classes (p>0.05). RHD patients had decreased serum Se and Zn element concentrations and increased serum Cu element concentration. We suggest that Se and Zn deficiency might be contributory factors in the development of rheumatic heart disease, and a high Cu concentration and a high Cu/Zn ratio might reflect an ongoing inflammatory process in this disease.     

Application of PIXE analysis to the study of the regional distribution of trace elements in normal human brain

A particle-induced X-ray emission (PIXE) analysis method is presented, which allows measurement of eight elements (i.e., K, Ca, Mn, Fe, Cu, Zn, Se, and Rb) in human brain samples of only a few mg dry weight. The precision and accuracy of the method were investigated by analyzing animal brain matter with both PIXE and instrumental neutron activation analysis (INAA). The method was applied to measure the 8 elements in 46 different regions of 3 human brains. The sections analyzed originated from either the left or the right cerebral hemisphere, brain stem, and cerebellum. For one of the brains, sections were also analyzed from 26 corresponding regions of both hemispheres. For all elements, similar concentrations were found in the corresponding areas of the left and right sides of the brain. The concentrations (in μg/g dry weight) of the elements K, Fe, Cu, Zn, Se, and Rb were consistently higher in cortical structures than in white matter. Deep nuclei and brain stem, which have a mixed composition, showed intermediate values for K, Zn, Se, and Rb. A hierarchical cluster analysis indicated that the various brain regions clustered into two large groups, one comprising gray and mixed matter regions and the other, white and mixed matter brain areas.     

Long-term changes in trace elements in patients undergoing chronic hemodialysis

Although the connection between aluminum intoxication and dialysis dementia was identified in the 1980s, understanding of trace element imbalances in hemodialysis patients is as yet incomplete. Recent application of newer inductively coupled plasma-mass spectrometry (ICP/MS) techniques has resulted in renewed study of this population. We used ICP/MS to evaluate serum concentrations of Cu, Se, Zn, Mn, and Ni in a relatively large population of hemodialysis patients compared with healthy age-matched controls. Comparison were also done by duration of hemodialysis treatment to see whether length of treatment correlates with severity of imbalance. Patients had significantly lower concentrations of the three elements Se, Zn, and Mn. Patients had significantly higher concentrations of Ni, and there was a positive correlation between duration and severity of imbalance for this one element. There was no difference in Cu concentrations between patients and controls. Our findings confirm relative Ni excess and deficiencies of Se, Zn, and Mn in hemodialysis patients, documenting the value of ICP/MS in research work on trace element imbalances as well as clinical monitoring of individual patients.     

Determination of plasma trace elements in tumor-bearing animals by proton-induced X-ray emission spectroscopy

Although altered levels of circulating essential trace elements are known to accompany malignant disease, the lack of sensitivity of conventional detection methods has generally limited their study to clinical conditions involving extensive disease (i.e., significant tumor burden). As such, the application of altered trace element levels as potential prognostic guides or as response indicators subsequent to treatment has been of limited use. During this study, proton-induced X-ray emission spectroscopy was evaluated as a tool to determine trace element imbalances in a murine tumor model. Using plasma from C57B1/6 mice bearing the syngeneic Lewis lung carcinoma (LLCa), levels of Fe, Cu, and Zn, as well as changes in the Cu/Zn ratio, were measured in animals carrying an increasing primary tumor burden. The plasma levels of Fe, Cu, and Zn were found to decrease significantly 7 d following implants of LLCa cells with no significant change observed in the Cu/Zn ratio. By d 21, however, an increase in the Cu/Zn ratio was found to accompany increased growth of the LLCa tumor; the plasma levels of Cu had returned to normal levels, whereas both the Fe and Zn plasma levels remained lowered. Collectively, the results suggest that although a net change in individual plasma trace element concentrations might not be accurately associated with tumor growth, a clear relationship was established between the Cu/Zn ratio and tumor size.     

Leukocyte selenium, zinc, and copper concentrations in preeclamptic and normotensive pregnant women

Preeclampsia is an important cause of maternal and perinatal mortality worldwide. The etiology of this relatively common medical complication of pregnancy, however, remains unknown. We studied the relationship between maternal leukocyte selenium, zinc, and copper concentrations and the risk of preeclampsia in a large hospital-based case-control study. One hundred seventy-one women with proteinuric pregnancy-induced hypertension (with or without seizures) comprised the case group. Controls were 184 normotensive pregnant women. Leukocytes were separated from blood samples collected during the patients’ postpartum labor and delivery admission. Leukocyte concentrations for the three cations were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations for each cation were reported as micrograms per gram of total protein. Women with preeclampsia had significantly higher median leukocyte selenium concentrations than normotensive controls (3.23 vs 2.80 μg/g total protein, p<0.0001). Median leukocyte zinc concentrations were 31% higher in preeclamptics as compared with controls (179.15 vs 136.44 μg/g total protein, p<0.0001). Although median leukocyte copper concentrations were slightly higher for cases than controls, this difference did not reach statistical significance (17.72 vs 17.00 μg/g total protein, p=0.468). There was evidence of a linear increase in risk of preeclampsia with increasing concentrations of selenium and zinc. The relative risk for preeclampsia was 3.38 (adjusted odds ratio [OR]=3.38, 95% confidence interval [CI]=1.53–7.54) among women in the highest quartile of the control selenium distribution compared with women in the lowest quartile. The corresponding relative risk and 95% CI for preeclampsia was 5.30 (2.45–11.44) for women in the highest quartile of the control zinc distribution compared with women in the lowest quartile. There was no clear pattern of a linear trend in risk with increasing concentration of leukocyte copper concentrations (adjusted for linear trend in risk =0.299). Our results are consistent with some previous reports. Prospective studies are needed to determine whether observed alterations in selenium and zinc concentrations precede preeclampsia or whether the differences may be attributed to preeclampsia-related alterations in maternal and fetal-placental trace metal metabolism.     

Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability

The effects of latent iron deficiency combined with parenteral subchronic or acute cadmium exposure during pregnancy on maternal and fetal tissue distribution of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant Sprague-Dawley rats were fed on semisynthetic test diets with either high iron (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg cadmium (as anhydrous CdCl₂) per kilogram body weight. Animals were exposed to cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection (Acute exposure). All rats were killed on gestation day 19. Blood samples, selected organs and fetuses were removed and prepared for element analyses by atomic absorption spectrometry. Low iron diet caused decreases in maternal body weight, maternal and fetal liver weights, placental weights and tissue iron concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium concentrations were increased and the increase was dose-related, maternal liver and kidney zinc concentrations were increased, and fetal zinc concentration was decreased. Cadmium concentration in maternal liver was additionally increased by low iron diet. Acute cadmium exposure caused lower maternal body and organ weights, high fetal mortality, and decreased fetal weights of survivors. In conclusion, parenteral cadmium exposure during pregnancy causes perturbations in essential elements in maternal and fetal compartments. Acute cadmium exposure in the last trimester of gestation poses a risk for fetal viability especially when combined with low iron in maternal diet.     

Uptake and distribution of trace metal elements in wheat seedlings

The uptake and distribution of eight metallic elements were examined in wheat seedlings for a period of 12 d with a radioactive multitracer technique. The radioactive nuclides of the seedlings were simultaneously determined by γ-ray spectrometry. All of the elements studied were taken up by the wheat seedlings and mainly accumulated in the roots. Only some elements were transported to shoots and leaves of the seedlings or bound to leaf proteins, and two elements were transported into the chloroplast. Uptake of most elements reached a maximum on the fifth or the eighth day and then gradually decreased afterward. In the cases of ^95mTc and ⁷²Se, the uptake increased continuously within 12 d without the peak uptake. The change of elemental concentrations was dependent on uptake and excretion rates. The dynamics of metal elements taken up by the wheat seedlings and their distribution in roots, shoots, and leaves were different for each element, suggesting that it may depend on the characteristics of the elements.     

氮磷肥对茶树锌硒等中微量元素吸收与分配的影响

锌（Zn）和硒（Se）及其他中微量元素（铝Al,钙Ca,铁Fe,铜Cu,锰Mn）是茶叶品质的重要指标,但茶树吸收Zn、Se能力及氮（N）磷（P）肥影响中微量元素吸收与分配的过程尚不清楚。以红壤丘陵区福鼎大白茶树为研究对象,开展Zn+Se、Zn+Se+N、Zn+Se+P、Zn+Se+N+P和对照共5种处理3次重复随机化区组试验,处理第3年春季分茶叶、成熟叶、吸收根、运输根和储藏根采集植物样品,测定其元素含量。结果表明,茶树地上和地下器官Zn和Se及其他中微量元素对N、P、Zn、Se添加的响应具分异性。与对照相比,茶树地上和地下器官Zn和Se含量均显著增加,与Zn+Se相比,施N和/或P肥仅显著提高茶叶和成熟叶Se含量（P<0.05）;与对照相比,施肥处理均显著提高吸收根和运输根Al、Fe含量以及储藏根Cu含量;运输根Mn含量表现为Zn+Se+N、Zn+Se+P、Zn+Se+N+P显著高于对照,储藏根Mn含量为Zn+Se+N+P显著高于其他处理;茶树各器官Ca含量对施肥处理无显著响应。此外,茶叶和成熟叶的Zn含量与吸收根显著正相关,而Se含量则与储藏根显著正相关。茶树具有吸收和积累Zn和Se的能力,而施N、P肥有助于提高茶叶Se含量,研究结果为红壤丘陵区培育高品质锌硒茶及营建生态高值茶园提供了依据。     

Serum levels of trace elements and iron-deficiency anemia in adult Vietnamese

This study was aimed at assessing the serum levels of vitamin A, copper, zinc, selenium, and iron among adult Vietnamese with and without iron-deficiency anemia. Blood was collected from adult Vietnamese living in the midland of northern Vietnam. One hundred twenty-three subjects in the age range 20–60 yr were included in the study. Anemia, where the concentration of hemoglobin in whole blood is less than 120 g/L in females and 130 g/L in males, was found in 30% (37/123) of the study population. The levels of vitamin A and selenium in the sera of anemic subjects (n=37) were significantly lower than that in nonanemic group (n=86). On the other hand, no significant differences were observed in the concentrations of copper and zinc between the two groups. This study was the first to show serum levels of trace elements in adult Vietnamese, providing useful baseline information for further studies.     

Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl₄)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl₄ to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.     

Trace elements in viral hepatitis

In this study, serum trace elements, including selenium (Se), zinc (Zn), copper (Cu), were determined by using Atomic Absorption Spectrophotometer (SpectrAA 250 Plus Zeeman, Varian, Australia) in sera of patients with viral hepatitis (A, B, C, D, E) cases (n = 102), and statistically compared with the controls (n = 52). In viral hepatitis, Cu levels were found as 3.23 ± 1.02 mg/L, and this value was significantly higher than the control group (1.13 ± 0.21) (p < 0.01). Both, Se and Zn levels found to be significantly low in viral hepatitis cases (p < 0.01). While Se level was 81.4 ± 26.01 μg/L in viral hepatitis (n = 101), it was found to be 166.15 ± 4.58 μg/L in healthy individuals. Meanwhile, Zn levels were 0.230 ± 0.081 mg/L and 0.748 ± 0.392 mg/L in hepatitis cases (n = 101) and the control group, respectively. There was no difference amongst viral hepatitis groups classified in regard with agents and clinical manifestation, such as A, acute hepatitis B, chronic hepatitis B, C, D and E. Previously, it was indicated that absorption disorders in gastrointestinal system, especially in chronic cases, were not main causes of decrease of trace elements by iron and several other parameters in sera of the cases. Therefore, we suggest that decrease in Zn and Se levels and elevation in Cu levels are probably resulted from defence strategies of organism and induced by the hormone-like substances.     

Role of trace elements in primary arterial hypertension

A negative relationship between water hardness and cardiovascular mortality rate was demonstrated and became a source of interest regarding minerals and trace metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and arterial hypertension. Higher incidences of sudden death, cerebrovascular diseases, arterial hypertension, and coronary heart disease have been reported in soft water areas. A major research effort has been devoted to the problem in an attempt to find a protective factor in hard water or a detrimental factor or element in soft water. The roles of calcium, magnesium, cobalt, lithium, vanadium, silicon, manganese, and copper have been considered potentially beneficial, whereas those of cadmium, lead, silver, zinc, and antimony have been considered potentially harmful. Cobalt and zinc have been attributed both roles. In the present article, the role of trace quantities of several elements in mineral water in the etiopathogenesis of primary arterial hypertension is reviewed. An erratum to this article is available at .