Serum copper-to-zinc ratio is associated with heart failure and improves risk prediction in middle-aged and older Caucasian men: A prospective study

Background and aimsSerum copper (Cu) and zinc (Zn) may play a role in the development of adverse cardiovascular outcomes including heart failure (HF). Serum Cu/Zn-ratio has been shown to be a risk indicator for cardiovascular disease, but its relationship with HF has not been previously investigated. We aimed to assess the association between Cu/Zn-ratio and incident HF risk using a prospective cohort study.Methods and resultsStudy participants were recruited in eastern Finland with baseline examinations carried out between March 1998 and December 2001. Serum levels of Cu and Zn were measured using atomic absorption spectrometry in 1866 men aged 42–61 years without a history of HF at baseline. Multivariable-adjusted hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident HF. During 26.5 years median follow-up, 365 HF cases occurred. Restricted cubic splines suggested linear relationships of serum Cu/Zn-ratio, Cu and Zn with HF risk. A unit increase in Cu/Zn-ratio was associated with an increased HF risk in analysis adjusted for several potential confounders including nutritional factors such as total energy intake, intake of fruits, berries and vegetables, and red meat (HR 1.63; 95% CI 1.06–2.51). The corresponding multivariable-adjusted HRs (95% CIs) for serum Cu and Zn were 2.42 (1.32–4.44) and 1.34 (0.50–3.63), respectively. Addition of Cu/Zn-ratio to a HF risk prediction model was associated with improved risk prediction.ConclusionIn middle-aged and older Finnish men, increased serum Cu/Zn-ratio is associated with an increased risk of HF in a linear dose-response fashion and might improve HF risk assessment.     

Cellular copper content modulates differentiation and self-renewal in cultures of cord blood-derived CD34+ cells

Several clinical observations have suggested that copper (Cu) plays a role in regulating haematopoietic progenitor cell (HPC) development. To further study this role we used an ex vivo system. Cord blood-derived CD34+ cells were cultured in liquid medium supplemented with Kit- ligand, FLt3, interleukin 6 (IL-6), thrombopoietin and IL-3. Under these conditions, Cu content, measured by atomic absorption, was 7 ng/10(7) cells. Modulation of intracellular Cu was achieved by supplementing the cultures with the Cu chelator tetraethylenepentamine, which reduced cellular Cu (4 ng/10(7) cells), or ceruloplasmin or Cu sulphate that elevated cellular Cu (18 and 14 ng/10(7) cells respectively). The results indicated that low Cu content delayed differentiation, as measured by the surface antigens CD34, CD14 and CD15, colony-forming unit (CFU) frequency and cell morphology, while high Cu accelerated differentiation compared with Cu unmanipulated cultures. As a result, expansion of total cells, CFU and CD34+ cells in low Cu was extended (12-16 weeks), and in high Cu was shortened (2-4 weeks), compared with control cultures (6-8 weeks). These effects required modulation of intracellular Cu only during the first 1-3 weeks of the culture; the long-term effects persisted thereafter, suggesting that the decision process for either self-renewal or differentiation is taken early during the culture. This novel method of controlling cell proliferation and differentiation by copper and copper chelators might be utilized for ex vivo manipulation of HPC for various clinical applications.     

Determination of zinc, copper, iron and zinc/copper ratio in the hair of active pulmonary tuberculosis patients

The determination of zinc (Zn), copper (Cu), iron (Fe) and zinc/copper ratio (Zn/Cu) in hair in 70 active pulmonary tuberculosis and 51 healthy individuals were reported. The Zn and Zn/Cu in hair of patients with pulmonary tuberculosis, in cases with cavities or noncavities and in cases with smear positive or negative sputum were lower than that of healthy individuals (P less than 0.01). But there was no difference in the hair Fe between the patients and healthy individuals.     

Beneficial effects of dietary copper supplementation on serum lipids and antioxidant defenses in rats

BACKGROUND: A nutrition experiment was utilized to investigate the effects of two levels of dietary copper (Cu) supplementation on lipid profile and antioxidant defenses in serum of rats. METHODS: Male Wistar rats (180-200 g; n = 10) were divided into three groups: control group (A), fed a basal diet with 6 microg Cu/g, and rats fed a basal diet with Cu (CuSO4) supplementation from aqueous solutions, for 4 weeks at the final concentrations of 2 mg Cu/rat (B) and 3 mg Cu/rat (C). RESULTS: No significant changes were observed in final body weight, body weight gain, food consumption, total serum protein and high-density lipoprotein. Cu supplementation reduced the triacylglycerol (TG), total cholesterol and low-density lipoprotein (LDL-C). The LDL-C/TG ratio and total antioxidant substances (TAS) were higher in (B) and (C) groups than in (A) group. There was a positive correlation between Cu supplementation and ceruloplasmin levels. The markers of oxidative stress, lipid hydroperoxide and lipoperoxide were decreased with Cu supplementation. No alterations were observed in superoxide dismutase, indicating saturation of Cu enzyme site. The glutathione peroxidase activities (GSH-Px) were increased in both Cu-supplemented groups. Considering that a copper-selenium interaction can affect mineral availability of both elements, the effects of Cu on TAS and GSH-Px activities were associated with increased selenium disposal. Conclusions: Dietary Cu supplementation had beneficial effects on lipid profile by improving endogenous antioxidant defenses and decreasing the oxidative stress in vivo.     

贵州省水城县地方性氟中毒病区骨软化畸形儿童铝氟及其他微量元素水平检测分析

目的 对贵州省水城县勺米乡与纸厂乡结合部地方性氟中毒(简称地氟病)村聚集性骨软化畸形儿童进行氟(F)、铝(Al)等多种元素测定,结合临床表现进行病因学诊断.方法 2008年11月,对水城县纸厂乡与勺米乡结合部地氟病村寨骨软化畸形少年儿童聚集病例(病例组),在严格质量控制基础上,采集14个病例和同县非地氟病区13个同龄对照(对照组)的任意1次尿和枕部贴皮头发,进行氟(F)、铝(Al)、镉(Cr)、锰(Mn)、铁(Fe)、铜(Cu)、锌(Zn)、砷(As)、硒(Se)、锶(Sr)、钡(Ba)10种元素检测,数据用PEMS 3.1医学软件统计包进行处理.结果 病例组尿中F、Al、Mn、Cu、Sr、Se水平(1.18 mg/L,112.6 μg/L,6.62、29.86 mg/L,177.5、4.23ng/L)与对照组(0.48、47.1、2.04、16.61 mg/L,55.17、15.52 ng/L)比较,差异均有统计学意义(t值分别为4.592、2.486、4.850、2.210、2.078、2.912,P均＜0.05).病例组头发中Al、Mn、As、Sr、Ba、Fe、Se水平(59.27、5.26、0.956、1.497、1.287、297.13、0.454 mg/kg)与对照组(18.69、0.72、1.094、0.621、0.675、69.022、1.323 mg/kg)比较,差异有统计学意义(t值分别为4.583、6.318、3.309、2.704、5.606、6.294,P均＜0.05).病例组尿中F与Al、Zn、As、Se的相关系数(r)均＞0.662(P均＜0.05),Al与Cu、Zn、As、Sr、Ba、Se的r均＞0.674(P均＜0.05),Se与Mn、Ba、Cu、Zn、Sr、As的r均＞0.694(P均＜0.05),Mn、Sr、As、Ba彼此之间r均＞0.550(P均＜0.05).病例组头发中Al与Mn、Cr、Fe、Cu、As、Se的r均＞0.732(P均＜0.05),Ba与Mn、Cr、Fe、Sr,Mn与Cr、Fe,Cr与As,Cu与Sr的r均＞0.686(P均＜0.05);对照组尿Cu与Zn、Se、Ba,Zn与Se、Ba,Cr与Mn、Ba的r均＞0.516(P均＜0.05);对照组头发中Al与Mn、Fe、Cu、As、Se,Se与Fe、Cu、As,Fe与Mn、Cu、As,Cu与Zn、As,Zn与As的r均＞0.739(P均＜0.05).病例组尿F与Se的r(0.762)与对照组(-0.469)比较,差异有统计学意义(u=2.079,P＜0.05).结论 水城县纸厂乡与勺米乡结合部地氟病病村寨骨软化畸形儿童的氟、铝负荷过高,尿和头发多种元素水平及其相关性分析与地方性铝氟中毒Al、F水平引起多种元素水平变化及其相关性呈网络样加强的现象一致,结合病人生活环境,有与铝氟中毒相同的骨X线表现,可诊断为地方性铝氟中毒.病人尿和头发Se水平降低及与F、Al等相关性有显著差异的生物学意义有待进一步探讨.

Abstract：

Objective To investigate the levels of trace elements such as fluorine(F), and aluminium (Al)etc. of osteomalacia malformation children and to make etiological diagnosis in reference with clinical manifestations.Methods Urine and occipitalia hairs of 14 diseased children(patient group) from endemic fluorosis area and 13 healthy children(control group) from non-endemic area were included in the study on November, 2008, and contents of 10 elements of fluorine(F), aluminum(Al), chromium(Cr), manganese(Mn), ferrum(Fe), cuprum(Cu), zinc(Zn), arsenic (As), selenium(Se), strontium(Sr), and barium(Ba) were tested. The data were analyzed with medical soft package PEMS 3.1. Results Urinary contents of F, Al, Mn, Cu, Sr, and Se(1.18 mg/L, 112.6 μg/L,6.62,29.86 mg/L, 177.5,4.23 ng/L) in patient group were significantly different from those in control group (0.48,47.1,2.04,16.61 mg/L, 55.17,15.52 ng/L, t = 4.592,2.486,4.850,2.210 2.078,2.912, all P＜ 0.05); Hair contents of Al, Mn, As, Sr, Ba, Fe, and Se in patient group(59.27,5.26,0.96,1.50,1.29,297.13,0.45 mg/kg)were significantly different from those of control group( 18.69,0.72,1.09,0.62,0.68,69.02,1.323 mg/kg, t = 4.583,6.318,3.309,2.704,5.606,6.294, all P ＜ 0.05); in patient group, the correlation coefficients of urinary Fe to Al,Zn, As, and Se were all bigger tan 0.662(all P＜ 0.05), those of urinary Se to Mn, Ba, Cu, Zn, Sr, and As were all bigger than 0.694(all P＜ 0.05), those among urinary Mn, Sr, As, and Ba were bigger than 0.550(all P＜0.05), those of hair Al to Mn, Cr, Fe, and Cu were bigger than 0.732(all P＜ 0.05), those of hair Ba to Mn,Cr, Fe, and Sr, and of hair Mn to Cr and Fe, and those between Cr and As, between Cu and Sr were all bigger than 0.686 (all P ＜ 0.05). In control group, the correlation coefficients of urinary Cu to Zn, Se, and Ba, those of Zn to Se and Ba, and those of Cr to Mn and Ba were all bigger than 0.516(all P ＜ 0.05), those of hair Al to Mn,Fe, Cu, As, and Se, and those of hair Se to Fe, Cu, and As, those of hair Fe to Mn, Cu, and As, those of hair Cu to Zn and As, and that between Zn and As were bigger than 0.739(all P ＜ 0.05). The correlation coefficient of urinary F to Se in patient group(0.762) was significantly different from that in control group( - 0.469, u = 2.079,P ＜ 0.05). Conclusions The burden of F and Al of osteomalacia malformation children in endemic fluorosis area of Shuicheng county is too high. The contents of multi-elements in urine and hairs and their correlation are coincident with high levels of Al and F and they cause network increase of multi-element content changes and their correlation. According to bone X-ray features combining with the living environment, the diagnosis of endemic Al-F fluorosis can be made. The biological significance of reducing urinary and hair Se levels and the correlations of F and Al need to be further studied.     

胃癌患者血清,组织和血细胞锌,铜,硒的含量变化

本文应用原子吸收检测技术对３２例胃癌患者的血清、胃癌组织、红细胞、白细胞和血小板锌、铜、硒的含量进行检测，与胃炎组比较，结果：胃癌组血清锌含量降低（Ｐ＜０．０１），而血清铜含量和血清Ｃｕ／Ｚｎ比值升高（Ｐ＜０．０１），血清硒含量降低（Ｐ＜０．０１）；白细胞锌含量降低（Ｐ＜０．０１），白细胞铜无显著变化；红细胞、血小板锌、铜、硒含无显著变化；胃癌组织中锌、硒含量增加（Ｐ＜０．０５），而铜含量无显著变化；锌、铜、硒及血清Ｃｕ／Ｚｎ比值与胃癌细胞分化程度以及有无肿转移无相关性。测定胃癌患者血清、组织、白细胞锌、铜、硒含量，可以估价体内这些元素的总体状态，为观察病情、估计预后提供依据。     

Copper amplification of prostaglandin E2 stimulation of the release of luteinizing hormone-releasing hormone is a postreceptor event.

We have shown that copper amplifies prostaglandin E2 (PGE2) stimulation of luteinizing hormone-releasing hormone (LH-RH) from explants of the median eminence area (MEA) and that this process is calcium-dependent. Since a Ca-cAMP pathway has been implicated in PGE2 action on the LH-RH neuron, in this study we wished to ascertain if copper exerts its effect on the PGE2 receptor or on a postreceptor component involved in PGE2 action. MEA of adult male rats were incubated for 5 min with 200 microM Cu/histidine (CuCl2 mixed with L-histidine at an equimolar ratio) and then incubated for 15 min either with 10 microM PGE2 (Cu/PGE2), 100 microM forskolin (Cu/forskolin), or 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (Cu/cAMP). Controls were incubated without Cu/histidine or with Cu/histidine alone. Basal release of LH-RH was 4.6 +/- 0.45 pg/15 min per MEA (mean +/- SEM). Net stimulated release during the 15-min exposure to PGE2, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate was 3.6 +/- 0.52, 3.1 +/- 0.39, and 1.6 +/- 0.42 pg/15 min per MEA, respectively. Net stimulated release after exposure to Cu/PGE2, Cu/forskolin, or Cu/cAMP was 12.7 +/- 2.2, 9.9 +/- 1.46, and 1.4 +/- 1.9 pg/15 min per MEA, respectively, indicating that copper amplifies the action of PGE2 and forskolin but not cAMP action. When MEA were exposed to a mixture of PGE2 and forskolin for 15 min, the effects of these two secretagogues on LH-RH release were not additive, regardless of whether the MEA were pretreated with Cu/histidine. In contrast to PGE2 and forskolin, copper did not amplify K+ stimulation of LH-RH release and, moreover, when Cu/histidine-treated MEA were exposed to a mixture of PGE2 and 30 mM K+, the effects of these two secretagogues were additive. These results are supportive of the proposition that PGE2 stimulation of LH-RH release is mediated by the Ca-cAMP pathway and that copper amplification of PGE2 action is a postreceptor event.     

The levels of copper, zinc and magnesium in type II diabetic patients complicated with foot infections

Changes in levels of trace elements and magnesium (Mg) may contribute to progression of diabetes mellitus (DM) and development of the complications. The aim of this study was to measure the levels of Copper (Cu), Zinc ( Zn), Mg and Cu/Zn ratios in diabetic foot infected patients (DFI) compared to controlled diabetic patients and healthy controls. 50 patients complicated with DFI, 50 controlled diabetic patients without any complications and 100 age and sex matched healthy subjects were enrolled in the study. Fasting plasma glucose, HbA1c, Cu, Zn and Mg were measured. One-Way ANOVA test was used to compare three different groups. Correlations between different variables were analysed using Pearson’s correlation coefficients(r). The mean values of Cu and Zn were higher in patients with DFI and DM compared to controls (P?<?0.001). Cu/Zn ratios were higher in DM compared to DFI and control groups (P?<?0.001). Serum Mg levels were lower in all diabetic patients. Elevation of Cu in DFI and DM groups was positively correlated with Cu/Zn ratios and elevation of Zn is negatively correlated. Our findings indicate an association between increased Zn concentrations and DFI.     

Serum copper and the risk of cardiovascular disease death in Finnish men

Background and aimsCopper (Cu) is a component of enzymes catalyzing oxidation-reduction reactions. With the persisting burden of cardiovascular disease (CVD), there is evident need to identify biomarkers and potential risk factors for CVD. We therefore examined the association between serum Cu levels and the risk of CVD death in Finnish men and across different body mass index (BMI) categories.Methods and resultsThis Finnish prospective study is based on 1911 men aged 42–60 years who were free of coronary heart disease at baseline. Cu concentrations (mg/l) were determined using atomic absorption spectrometer and categorized into quartiles (<1.0; 1 to <1.1; 1.1 to <1.21; ≥1.21). Participants were categorized into normal weight <25 kg/m², pre-obesity 25–29.9 kg/m², and obesity >30 kg/m². The association between Cu and CVD death was analyzed using multivariable Cox regression models. During a median follow-up of 25.8 years, 358 CVD deaths occurred. The risk of CVD death increased continuously with increasing Cu levels (for non-linearity, p = 0.64). Using the first quartile as reference after adjustment for covariates, the hazard ratios (HR) (95% confidence interval (CI)) for CVD death for Cu concentrations in second, third and fourth quartiles were 1.45(1.05–2.01), 1.69(1.25–2.27), and 1.68(1.23–2.29), respectively. Obese men in the third quartile of serum Cu concentrations had highest risk of CVD death (HR (95%CI) 2.71(1.27–5.78)).ConclusionElevated serum Cu level was associated with increased risk of CVD death across all BMI categories in middle-aged and older Finnish men. Serum Cu may have prognostic implication for CVD mortality risk; however, further studies are needed.     

单次尿铜比值诊断儿童肝豆状核变性意义初探

目的探讨单次尿铜比值测定代替24h尿铜定量用于诊断肝豆状核变性(WD)的可行性。方法测定正常儿童24小时内多次尿标本的铜肌酐(Cu/Cr)、铜/锌(Cu/Zn)比值,了解其稳定性;收集15例肝病患儿(其中2例WD)的晨尿和24h尿,研究单次尿Cu/Cr、Cu/Zn值与24h尿铜相关性;测定9例初发WD患儿和22例其它肝病患儿的单次尿铜比值和24h尿铜,研究其诊断儿童肝病中的WD的敏感度和特异度。结果2例正常儿童24h内尿Cu/Cr值和Cu/Zn值的变异系数分别为12.5%、9.3%。单次尿Cu/Cr值和Cu/Zn值与24h尿铜的相关系数分别0.767和0.891(P<0.001)。24h尿铜定量诊断WD的敏感度55.5%、特异度77.3%;晨尿Cu/Zn值的敏感度77.8%、特异度86.4%。结论单次尿铜比值1d内波动小,尿Cu/Zn值与24h尿铜定量相关性好,诊断WD的敏感度和特异度较高,可望代替24h尿铜定量用于WD诊断。     

Transmission of Venezuelan encephalitis virus by naturally infected Culex (Melanoconion) opisthopus

During August 1977 two of 975 Culex (Melanoconion) opisthopus collected from an enzootic marsh habitat on the Pacific coast of Guatemala transmitted VE virus to hamsters. Eight VE strains were isolated from Cu. opisthopus. The minimal level of VE infection in this species during July-August 1977 at La Avellana, Guatemala was 1/128 (8/1,021), and the prevalence of Cu. (Mel.) opisthopus transmitting VE virus was 1/487 (2/975). This mosquito was the predominant species attacking humans at that time, suggesting that Cu. opisthopus is a vector of VE virus to man as well as a vector in enzootic cycles in Guatemala. These studies establish Cu. opisthopus as the third proven enzootic vector of VE virus.     

Superoxide dismutase and catalase inhibit oxidized low-density lipoprotein-induced human aortic smooth muscle cell proliferation: role of cell-cycle regulation, mitogen-activated protein kinases, and transcription factors

Several antioxidant enzymes, including copper, zinc-superoxide dismutase (Cu, Zn-SOD) and catalase, have been suggested to be protective against the proliferation of vascular smooth muscle cells exposed to oxidative stress. In the present study, we investigated effects of Cu, Zn-SOD and/or catalase on oxLDL-induced proliferation of, and intracellular signaling in, human aortic smooth muscle cells (HASMCs). HASMCs were transfected with adenovirus carrying the human Cu, Zn-SOD gene and/or the human catalase gene. This resulted in a high level of Cu, Zn-SOD and/or catalase overexpression and decreased oxLDL-induced proliferation. Cu, Zn-SOD and/or catalase also arrested cell cycle progression, which was associated with decreased expression of cyclin D1, cyclin E, CDK2, and CDK4 and upregulation of p21(Cip1) and p27(Kip1). Phosphorylation studies on ERK1/2, JNK, and p38, three major subgroups of mitogen activator protein kinases, demonstrated that Cu, Zn-SOD and/or catalase overexpression suppressed ERK1/2 and JNK phosphorylation. Gel-mobility shift analysis showed that oxLDL caused an increase in the DNA binding activity of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB), which was inhibited by Cu, Zn-SOD and/or catalase overexpression. These results provide the first evidence that overexpression of Cu, Zn-SOD and/or catalase in HASMCs attenuates the cell proliferation caused by oxLDL stimulation and that this inhibitory effect is mediated via downregulation of ERK1/2 and JNK phosphorylation and AP-1 and NF-kappaB inactivation. These observations support the feasibility of the increase of Cu, Zn-SOD and/or catalase expression in human smooth muscle cells as a means of protection against oxidant injury.     

A correlation between the ligand specificity for 67copper uptake and for copper-prostaglandin E2 stimulation of the release of gonadotropin-releasing hormone from median eminence explants

We have previously shown that copper (Cu) leads to a 3- to 4-fold amplification of prostaglandin E2 (PGE2) stimulation of LHRH release from explants of the median eminence area (MEA), that this amplification is a saturable function of [Cu], and that complexed Cu but not ionic Cu is the active form of the metal. This implicates a ligand-specific site in Cu action. In this study we address the following questions. Is there a ligand specificity for Cu amplification of PGE2 stimulation of LHRH release, and if so, does it correlate with the ligand specificity for Cu uptake? MEAs of 1-month-old female rats were incubated for 5 min with 150 microM Cu solution and then for 15 min with 10 microM PGE2 (Cu/PGE2); LHRH released into the medium was evaluated by RIA. To assess Cu uptake, MEAs were incubated with 100 microM67 Cu solution for 15 min, and 67Cu accumulation by the MEA was evaluated. The Cu was complexed to one of the following ligands: histamine, His, Cys, Thr, Gly, glutathione, Gly-His-Lys, or albumin. There was a high degree of correlation (r = 0.943) between the ligand specificity for Cu/PGE2 stimulation of LHRH release (Cu action) and 67Cu uptake. Complexation of ionic Cu with His facilitated Cu action and 67Cu uptake 3-fold each, and this was completely prevented by the inclusion of His in a 100-fold excess over the concentration of the Cu/His complex. Histamine, the amino acids, and the peptides facilitated Cu action and 67Cu uptake, whereas albumin did not do so. Of these facilitatory ligands, histamine and His were the most effective and Gly-His-Lys was the least effective. In summary, both 67Cu uptake and Cu action are ligand-dependent and ligand-specific; the Cu interactive sites have a common recognition for the Cu-ligand complex and for the ligand itself; and the ligand specificity for 67Cu uptake and for Cu action are highly correlated. These results are consistent with the ligand specificity for Cu uptake being the primary determinant of the ligand specificity for Cu/PGE2 stimulation of LHRH release.     

Crystallographic Characteristic Effect of Cu Substrate on Serrated Cathode Dissolution in Cu/Sn–3.0Ag–0.5Cu/Cu Solder Joints during Electromigration

The crystallographic characteristic effect of Cu substrate on cathode dissolution behavior in line-type Cu/Sn–3.0Ag–0.5Cu (SAC305)/Cu solder joints during electromigration (EM) was investigated by scanning electron microscope (SEM), electron backscatter diffraction (EBSD), and first-principles calculations. The SEM and EBSD results show that the crystallographic characteristic of Cu substrate is crucial to cathode dissolution behavior under a direct current of 1.5 × 10⁴ A/cm² at 125 °C ± 2 °C. When the (001) plane of copper grain adjacent to the Cu₃Sn/Cu interface is perpendicular or nearly perpendicular to the current direction, local cathode dissolution tips are easily formed, whereas the (111) plane remains mostly undissolved, which finally leads to the inhomogeneous cathode serrated dissolution in the substrate. The first-principles calculation results reveal that the different surface energies and energy barriers of the different crystallographic planes of Cu grains in the substrate are responsible for the local cathode dissolution tips. Adjusting the copper grain in a substrate to a crystal plane or direction that is difficult to dissolve during EM is a promising method for improving the reliability of solder joints in the future.     

Method of dialysis therapy and selected markers of oxidative stress and endothelial injury in patients with chronic renal failure

Cardiovascular diseases (CVD), being mostly a clinical manifestation of atherosclerosis, are the main cause of mortality in patients with chronic renal failure (CRF). It is now generally accepted that the first step in atherosclerosis is endothelial dysfunction. Recently, oxidative stress (SOX) has been implicated as an important etiologic factor in atherosclerosis and vascular dysfunction both in general and uremic populations. The aim of the present study was to establish the effect of two different method of dialysis therapy: hemodialysis (HD) and continuous peritoneal dialysis (CAPD) on the markers of SOX: lipid peroxides, Cu/Zn superoxide dismutase (Cu/Zn SOD) and autoantibodies against oxidized LDL (OxLDL-Ab), and endothelial injury: antigen of the von Willebrand factor (vWF : Ag), soluble thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) in 43 patients with CRF. Compared with the control subjects, patients with CRF showed a significant increase in plasma concentrations of Cu/Zn SOD, which was more elevated in HD than in CAPD group. The lipid peroxide levels were increased only in the post-HD samples, whereas OxLDL-Ab were more elevated in HD than in CAPD group. Markers of endothelial injury were significantly higher in dialyzed patients relative to controls, and were positively correlated themselves as well as with Cu/Zn SOD levels. The patients on HD and CAPD are exposed to increased SOX as well as to endothelial injury. The association between Cu/Zn SOD and the endothelial injury markers suggests the possible effect of oxidative stress on endothelial dysfunction in CRF patients.     

Blood activity of Cu/Zn superoxide dismutase, glutathione peroxidase and catalase in Alzheimer's disease: a case-control study

Cu/Zn superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPx) and catalase, which are the three main enzymes involved in cellular protection against damage due to oxygen-derived free radicals have been assayed in plasma and erythrocytes obtained from subjects with dementia of the Alzheimer type (DAT) and from controls. Blood samples were obtained from 25 patients with DAT and from age-matched subjects without diagnoses of neurological disease (non-DAT), as well as from younger individuals (reference group). Using appropriate statistical procedures, the three enzyme activities measured in blood of the elderly were decreased if compared to the younger reference group. Moreover, a significant increase in erythrocyte Cu/Zn SOD and catalase activities of DAT patients was observed compared to the non-DAT group. These results are discussed taking the free radical theory of aging into consideration.     

Evaluation of serum metallothionein-1, selenium, zinc, and copper in Ghanaian type 2 diabetes mellitus patients

Metabolic disturbances of trace elements may be implicated in the complications of type 2 diabetes mellitus (T2DM). The aim of the study was to determine the level of Zinc (Zn), Selenium (Se), Copper (Cu) and the metal binding protein Metallothionein-1 (MT-1) in T2DM. Fifty-five (55) T2DM subjects and 30 Controls (C) were studied for, Se, Zn, Cu and MT-1. Zn, Se and Cu were analyzed using Flame Atomic Absorption Spectroscopy. Mean FBG in the T2DM and C groups were 183?±?5 mg/dl and 88?±?5 mg/dl, respectively. Mean Se, Zn and Cu levels in the T2DM group were 204?±?91 μg/l, 407?±?117 μg/l and 1,337?±?527 μg/l, respectively. The control group had Se, Zn and Cu levels of 123?±?25 μg/l, 750?±?190 μg/l and 989?±?197 μg/l, respectively. While Zn levels in T2DM were half that of the C, Se levels were?≈?2-fold. Se, Zn and Cu differences between the two groups were statistically significant (P?=?0.000; P?=?0.000, P?=?0.000, respectively). The metabolic derailment of MT-1 in the T2DM group showed a wide variation with the T2DM having significantly lower MT-1 values (P?=?0.000). A negative correlation was seen between Cu and Zn in the T2DM group (P?=?0.022). A standardized canonical discriminant function was obtained as D?=?0.823*FBG?0.149*MT?0.457*Zn?+?0.172*Cu?+?0.362*Se with contributions of FBG?>?Zn?>?Se?>?Cu?>?MT-1. In conclusion, alterations in the levels of Zn, Se and Cu were observed in Ghanaian T2DM patients.     

Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study

Aims/IntroductionWe aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes.Materials and MethodsA cross‐sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin‐to‐creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of < 60 mL/min/1.73 m². Areas under the curves (AUCs), cutoff values, and thresholds for detecting DKD were determined for the Cu/Zn ratio, soluble tumor necrosis factor‐α receptor 1 (sTNFαR1), and high‐sensitivity C‐reactive protein (hsCRP). Patients were categorized by each cutoff value of sTNFαR1 and the Cu/Zn ratio. Odds ratios (ORs) and biological interactions for the prevalence of DKD were determined.ResultsDKD was identified in 220 patients. AUC/optimal cutoff values were 0.777/1300 pg/mL for sTNFαR1, 0.603/1.1648 for the Cu/Zn ratio, and 0.582/305 ng/mL for hsCRP. The ORs for DKD were higher, but not significantly, in the sTNFαR1 < 1300 and Cu/Zn ≥ 1.1648 group, significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P < 0.0001), and further synergistically elevated in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group (P < 0.0001) compared with the sTNFαR1 < 1300 and Cu/Zn < 1.1648 group after multivariable adjustment. Levels of sTNFαR1 were significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group than in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P = 0.0006).ConclusionsUnder an inflammatory initiation signal of elevated serum sTNFαR1 levels, an increase in the Cu/Zn ratio may further exacerbate inflammation and is synergistically associated with a high prevalence of DKD in patients with type 2 diabetes.     

The value of serum zinc, copper, ceruloplasmin levels in patients with gastrointestinal tract cancers.

BACKGROUND/AIMS: Gastrointestinal cancers are frequent diseases of particular importance for surgeons with regard to their management and follow-up. Neoplastic diseases activate antioxidant defense systems. As a result, concentrations of redoxal enzymes and their co-factor elements appear to change. The levels of zinc (Zn), copper (Cu) and ceruloplasmin have been found to be critical parameters. In addition, it seems to be important to consider the Cu/Zn ratio in such cases. In this study, changes in the levels of Cu, Zn and ceruloplasmin in patients with gastrointestinal system cancers was evaluated, and the proportion of Cu to Zn (Cu/Zn) is discussed. METHODS: In this clinical trial, levels of Cu and Zn were defined with calorimetric methods and ceruloplasmin levels were measured with immunohistochemical methods in a control group of 20 healthy individuals and in 25 patients who underwent surgery for gastrointestinal system cancer. The blood samples were taken preoperatively in gastrointestinal system cancer patients. RESULTS: This study has shown that while the decrease in Zn levels and the increase in ceruloplasmin levels in patients with gastrointestinal system cancers were found to be significant (p<0. 001, p=0. 014) when compared to the control group, the increase in the level of Cu was also found to be significant (p=0. 019). In the patient group, the correlations between serum Cu and serum ceruloplasmin proved to be significant (r=991, p<0. 001). The Cu/Zn ratio, when compared with Zn, ceruloplasmin and Cu, showed significant results (r= 0. 562, r= 0. 500, r=0. 506, p<0. 001). CONCLUSIONS: This study shows that serum Cu, Zn and ceruloplasmin levels show changes in gastrointestinal system cancers, but further research is needed to demonstrate the importance and significance of these parameters and their relation with other contributing neoplastic factors.