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The liver and the biliary tree form the main excretory route of manganese (Mn) and copper (Cu). Cholestasis, can lead to the accumulation of these trace elements in the organism, resulting in toxicity to the basal ganglia of the central nervous system. The aim of our study was to reveal the influence of long-term cholestasis on the Mn and Cu levels in the blood of patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). We recruited patients with PBC (n = 20) and PSC (n = 32). A control group (n = 40) was also set up. We also examined serum bile acid concentrations and liver enzyme activities. We did not observe any significant differences in any of these parameters between the PBC and PSC groups. The Mn and Cu levels in the PBC and PSC patients differed significantly from the that in the control group (p < 0.0001 and p <.021, respectively). Patients in whom the laboratory cholestasis markers normalized during ursodeoxycholic acid treatment (18/52;35%) presented with significantly lower levels of Mn and Cu (p =.015 and p =.012, respectively). Ten PSC patients showed normal levels of Mn and Cu six months after liver transplantation. Fine tremors, rigidity, dysarthria, and hypomimia were reported in nine (23%), eight (20%), four (10%), and eight (20%) patients, respectively. In addition to monitoring the cholestasis levels, liver function, and Mn and Cu levels during the long-term treatment of PBC and PSC patients, it is important to also regularly monitor the occurrence and development of extrapyramidal symptoms of Parkinson's-like syndromes. [ABSTRACT FROM AUTHOR]

Purpose: The amounts of calcium (Ca), magnesium (Mg), zinc (Zn), and copper (Cu) in enamel may be crucial for maintaining its integrity and to attenuate potential environmental effects on teeth. The aim of this study was to examine whether the mineral composition of enamel could influence tooth wear. Materials and Methods: A total of 50 patients with severe tooth wear were compared with 20 healthy volunteers. Tooth wear was assessed using clinical examination according to the protocol of Smith and Knight. Subsequently, the maxillary central incisors of each subject were subjected to acid biopsies to assess the mineral composition in the enamel. Atomic absorption spectroscopy with an air/acetylene flame was used to analyze for Ca, Zn, and Mg. Graphite furnace atomic absorption spectroscopy was used to analyze for Cu. Results: The concentrations of Ca and Mg in tooth enamel were comparable in the study and control groups. Zn enamel content was higher in patients with tooth wear, and Cu enamel content was lower in these patients compared with the control group. Conclusion: The differing Zn and Cu contents in tooth enamel might offer a reason for excessive tooth wear in these patients. However, the results require further, more detailed study. Int J Prosthodont 2013;26:423-428. [ABSTRACT FROM AUTHOR]

In the light of the newly established norms of copper content for pregnant meat-and-lard ewes, the effect of various levels of the content of this element in the diets of ewes on the digestibility and the use of nutrients in various periods of pregnancy has been determined during the physiological experiments. [ABSTRACT FROM AUTHOR]

β-Thalassemia is a hereditary blood disorder caused by mutations that affect the synthesis of the β-globin chain of red blood cell hemoglobin. Thalassemia can get an overload of iron in their bodies, either from the disease itself or from frequent blood transfusions. The study aims to evaluate the plasma trace elements and demonstrate the correlation between trace elements and zinc dependent enzyme in Beta Thalassemia patients. Subjects and methods: A cross sectional study was conducted on β-thalassemia major patients whom attended the thalassemia center in Azadi Teaching Hospital. This study was conducted at the first of March 2019 till the end of June 2019, at Kirkuk city - Iraq. Ninety subjects were participated in present study. The subjects were divided into 2 groups. group 1; Sixty thalassemia male patients age 15 to 30 years, transfusion dependent β-thalassemia patients . group 2; Thirty Normal healthy male subjects less than 30 years. Blood sample was taken from patients and control subjects. Serum was used for measurement of ferritin, AST, ALT, ALP, Zinc and copper. Results; The results showed that there was a highly significant elevation in the concentration of serum ferritin in thalassemia male patients as compare to normal control male subjects. There is a highly significant elevation in the serum activities of liver enzymes (AST, ALT and ALP) in thalassemia males when compared to control males. There is there is significant elevation in serum copper in thalassemia patients as compare with healthy controls. However, there was significant reduction in zinc level in thalassemia patients as compare with healthy control. [ABSTRACT FROM AUTHOR]

Examines the effects of intense endurance training on basal plasma and urinary calcium, magnesium, iron, zinc and copper levels in male competitive cyclists. Data on aerobic performance at baseline and following the volume phase, interval phase and unloading taper; Plasma mineral data at baseline; Urinary excretion data at baseline.

This paper presents the results of the design and implementation of a new geological tool, named as HUMGEOSTAT, for advanced geostatistical analysis of mineral deposit, a case study at the Sin Quyen, one of the important mines for the Vietnam mining industry in Vietnam. The tool is developed based on the Stanford Geostatistical Modeling Software (SgeMS) platform, which is an open-source computer package for solving problems involving spatially related variables. The tool is capable of supporting users in reducing uncertainty and improving the quality of mining exploration tasks. The tool has all the functions needed to solve a complete geostatistical issues i.e. Variogram models (such as Spherical, Exponential, Gausian, Linear and Pure nugget effect); and four commonly used Kriging methods (Ordinary Kriging, Simple Kriging, Indicator Kriging, Co-Kriging). The tool was applied to test various types of input data and particularly for complex copper ore bodies of Sin Quyen mine. The results of analysis of orebody spatial structure has found that Cu content has non-uniform change, regional anisotropy in north-south (0±22.50) direction, and anisotropic index is around 1.3. The mineral reserves are estimated according to sub-blocks and points in the orebody-space. The results indicate that the Ordinary Kriging (OK) has reliable results, variance estimation is small; the predicted result gained from OK have strong correlation (K=0.905) with ore samples. HUMGEOSTAT was applied at the Sin Quyen mine and various coal mines, the results were adapted with reality of mines. [ABSTRACT FROM AUTHOR]

In recent years, infrared radiation (IR) has been considered as one of the suitable methods for drying and decontamination of different spices. However, the low penetration depth of the IR limits its use for food processing in the industry. Due to the importance of Carum carvi as a spice with medical properties, this research aimed to determine the effect of the sample’s structure (powder and seeds), water activity (0.24, 0.56 and 0.89) and the power of IR emitter (222 to 960W) on the penetration depth of the IR into Carum carvi For this propose, the heat fluxes received by copper black body that placed under samples with different thickness was measured. Afterward, the penetration depth was calculated through a mathematical model. The results indicated while aw of the sample, the IR power, and their interaction had a significant effect on the penetration depth of the IR, the structural properties of the sample had no significant effect on it. Increasing the infrared power to 601W enhanced the penetration depth in all of the samples. The highest penetration depth into the powder and the seeds of Carum carvi with aw 0.24 was achieved at the IR power of 601W, and was recorded 4.07±0.27 and 3.85±0.23mm while the samples with aw 0.89 were shown the highest penetration depth when they were irradiated by IR power of 845W (4.12±0.18 and 4.09±0.13mm). According to the results, determining of IR penetration depth in the spice can be used to determine of their optimal thickness during the infrared food process. [ABSTRACT FROM AUTHOR]

Parameters of the metal plasma flow generated by a source with heated liquid anode have been studied during motion in axial magnetic field. It is established that the source operating on liquid copper as the working body creates a plasma flow with an ionization of degree about 8% and concentration reaching 4 × 1016 m–3 near the source output. The directed energy and width of the energy spectrum of ion flow can be varied in broad intervals by controlling the voltage applied to electrodes. [ABSTRACT FROM AUTHOR]

Abstract The determination of copper and iron in liver biopsies have important roles in the diagnosis of Wilson's Disease and haemochromatosis respectively. An external quality assurance scheme is essential for analytical validation of results, however, none was available for these analytes at the time of this investigation. Accordingly a pilot scheme was established. The results of this scheme and of a corresponding questionnaire are recorded. Twenty-nine identical sets of lyophilised certified reference materials or dried aliquots of livers purchased from local stores were distributed to 26 specialist trace element laboratories offering this clinical service. Using results returned, target values were assigned and analytical imprecision and accuracy were assessed. Laboratories were also asked to complete a questionnaire regarding details of sample preparation, analytical method and interpretation. Accuracy was worse than ± 50% at least one result in 38% of laboratories measuring copper and 57% measuring iron. Within-batch imprecisions poorer than ± 50% were found in 20% and 23% of liver copper and iron results respectively. Accuracy was found to be statistically poorer if sample weights less than 3 mg were measured. Reference ranges were frequently absent from reports or disagreed with international guidelines. A significant proportion of laboratories are unable to provide consistently reliable analytical performance to the extent that misdiagnosis may occur. The current diagnostic service is further compromised by the lack, or unreliability, of appropriate reference ranges provided on reports making interpretation more difficult. Without improvement, a review of current guidelines may be necessary. [ABSTRACT FROM AUTHOR]

Abstract Cerium and cerium containing materials have been drawing increasing attentions in industrial and biomedical applications in recent decades. The increased applications of cerium have also increased the risk of human body exposed to cerium ions. Due to its similar ionic radius to calcium(II), cerium(III) have found mainly deposited in the skeletal system. However, the effects of cerium(III) on the bone metabolism homeostasis remain poorly understood. In the present study, the effect of cerium(III) on the osteoclastogenesis which plays a pivotal role in bone metabolism homeostasis was investigated. Cerium(III) could enhance the expression and activity of NADPH oxidase1 (Nox1) leading to the elevation of intracellular reactive oxygen species (ROS) level. The augmentation of ROS level activated the RANKL dependent osteoclasts differentiation pathways resulted in the promotion of osteoclastogenesis, while anions associated with cerium(III) cation have no effects on the differentiation of osteoclasts. The cerium(III) activated osteoclasts exhibited enhanced bone resorption capability. These results provided fundamental information for understanding the potential effects of cerium(III) on the metabolism homeostasis of skeletal system which is of great reference value for future biomedical applications of cerium salts. [ABSTRACT FROM AUTHOR]

BACKGROUND: Copper (Cu) is an essential microelement to the health and proper functioning of metabolic processes in animals, but the particular function of Cu in fermentation processes and the formation of methane (CH4) in the rumen have been poorly analyzed. The innovative aspect of this study was to investigate the effects of high doses of Cu as copper sulfate on in vitro ruminal degradation, fermentation patterns, and CH4 production. RESULTS: There was a decrease (P < 0.04) on in vitro dry matter (DM) and organic matter degradability from 60 to 100 µg Cu/g DM. Ammonia concentration decreased drastically with increasing Cu levels (linear effect, P < 0.01). Total bacteria and volatile fatty acids (quadratic effect, P < 0.02) were reduced with 80 and 100 µg Cu/g DM. Methane production (milliliters per gram digestible organic matter) was decreased when dosages of Cu were increased (linear effect, P < 0.003). CONCLUSION: Overall, the addition of increasing levels of Cu to 40 µg Cu/g DM did not have an adverse impact on ruminal bacteria growth and decreased CH4 production, without affecting the ruminal kinetics. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Special staining and grading of canine liver cytology samples aids in detection of increased copper content. The prevalence of copper in routine diagnostic liver cytology samples, clinical findings associated with high cytologic copper (cCu) grade, and the correlation between cCu grade and histologic findings, including histologic copper (hCu) grade, are unknown. This data may be helpful in ascertaining when to determine a cCu grade and when interpreting cCu grade. Clinical data and available archived hepatic histologic and cytologic samples from 198 dogs were collected, evaluated, rhodanine stained, and graded for copper. Prevalence of increased cCu .5 in a randomly collected group of 163 individuals, and the correlation between cCu and clinical data (n = 198), hCu grade (n = 37), or findings on hematoxylin and eosin-stained hepatic sections (n = 32) were evaluated. The observed prevalence was 1.23%. Dogs with elevated alanine transaminase .180 IU/L or aspartate transaminase .90 IU/L and patients who subsequently had hepatic copper quantification were statistically more likely to have pathologic levels of copper detected by cytology. There was significant and modest correlation between cCu and hCu, interface hepatitis, portal inflammation, and fibrosis. Evidence of hepatocellular leakage may be indications for determination of cCu. [ABSTRACT FROM AUTHOR]

Abstract An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight β-lactam antibiotics using UV–Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These β-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecular oxygen to produce hydrogen peroxide. Finally, meropenem underwent degradation in the presence of copper. The analysis of activity against Escherichia coli and Staphylococcus aureus showed that the effects of meropenem, amoxicillin, ampicillin, and ceftriaxone were significantly hindered in the presence of copper ions. The interactions with copper ions should be taken into account regarding the problem of antibiotic resistance and in the selection of the most efficient antimicrobial therapy for patients with altered copper homeostasis. Graphical abstract fx1 Highlights • β-Lactam antibiotics showed coordination/redox interactions with Cu. • Ampicillin, amoxicillin, cephalexin and ceftriaxone formed stable Cu2+ complexes. • Cefaclor reduced Cu2+ to Cu1+, whereas meropenem underwent degradation. • Cu2+ decreased antimicrobial effects of meropenem, amoxicillin, and ceftriaxone. [ABSTRACT FROM AUTHOR]

Based on the high prevalence, diabetes mellitus (DM) is considered as a worldwide problem. More than 8.3 % of the world population is suffering from this disease. One of the causing factors of this disease can be the absence or imbalance of trace, essential elements. It can cause collapses of antioxidant defence and glucose intolerance. It plays a role in the pathogenesis and progression to diabetes mellitus. This review focuses on chromium, copper, selenium, vanadium, and zinc. Many studies deal with these elements but there is variability in opinions. Insulin-mimetic activity and ability to control the concentrations of blood glucose were confirmed. However, these effects were of more importance in patients with prediabetes. In patients with prediabetes, due to the supplementation of selected trace elements, it is possible to normalize the blood glucose level and prevent the development of diabetes mellitus. The importance of supplementation was confirmed for chromium and zinc. The supplementation of vanadium has a positive effect on the normalization of glycaemia but it is necessary to control the level as it can have toxic effects during long-term treatment. Conversely, higher copper concentrations in the body adversely affect patients and chelation therapy is needed. Selenium must be kept in the standard concentration and regular control of the concentration in the body is necessary. For this reason it is necessary to continue with analysis and the creation of new methodologies that could unify the view on the issue. [ABSTRACT FROM AUTHOR]

Abstract The oxidation of hydroquinones is of interest both due to the generation of reactive oxygen species (ROS) and to the implications to trace metal redox state. Menadione (MNQ), a typical toxicant quinone used extensively for studying the mechanisms underlying oxidative stress, is known to be an effective source of exogenous ROS. In this study, the kinetics and mechanism of the oxidation of menadiol (MNH 2 Q, the reduced form of MNQ) in the absence and presence of copper (Cu) over the pH range 6.0–7.5 was examined. The autoxidation rate increased with increasing pH and concentration of O 2 and also slightly increased with increasing concentration of MNH 2 Q and MNQ with Cu shown to play a significant role in catalysing the oxidation of MNH 2 Q. A kinetic model showed that the mono-deprotonated menadiol, MNHQ−, accounted for the pH dependence of the autoxidation rate. In this proposed mechanism, both MNH 2 Q and MNHQ− species were oxidized quickly by Cu(II), generating menadione semiquinone (MNSQ•−) and superoxide (O 2 •−) and the reduced form of Cu, Cu(I). Oxygen not only facilitated the catalytic role of Cu(II) by rapidly regenerating Cu(II) but also effectively removed MSNQ•−, generating the important chain-propagating species O 2 •−. The model demonstrated that Cu(I) was a significant sink of O 2 •− resulting in the generation of H 2 O 2 with subsequent generation of highly oxidative intermediates including Cu(III). These results provide considerable insight into the clinical significance of the biological activation and detoxification of MNQ with the kinetic model developed of use in identifying key processes in the generation of harmful oxidants in living systems. Graphical abstract Cu(I) catalyses the oxidation of menadiol to menadione with concomitant production of powerful oxidants including Cu(III). Unlabelled Image Highlights • Cu(II) significantly facilitates the oxidation of menadiol. • Mono-deprotonated menadiol (MNHQ−) is the kinetically active species. • O 2 •−-driven pathway is more important than comproportionation-driven pathway. • Model shows importance of MNSQ•− and O 2 •− with generation of H 2 O 2 and Cu(III). [ABSTRACT FROM AUTHOR]

Introduction: Diabetes is one of the most common chronic diseases. Gestational Diabetes Mellitus (GDM) is a type of diabetes that starts during pregnancy. Aim: To study the levels of chromium, iron, and copper in women with GDM compared with non-diabetic pregnant women. Materials and Methods: In this case-control study that was performed in Amir Al Momenin Hospital (Zabol-IRAN) in 2016 (from may to October). Sixty pregnant women with GDM were included in the study group and 60 non-diabetic pregnant women were included in the control group. Seven millilitres of blood was taken from the study participants for serum separation. For measuring the levels of chromium, iron, and copper Atomic Absorption Spectrometry was used. Data analysis was performed by Student's t-test using the Statistical Package for the Social Sciences (SPSS) software version 16. Results: Serum levels of chromium (7.76±2.83 vs 6.52±2.74 ng/dL), iron (0.60±0.10 vs 0.55±0.14 µg/dL) and copper (0.97±0.22 vs 0.83±0.22 µg/dL) were lower in the case group compared with the control group. Their difference was not statistically significant (p>0.05). The average age of participitants was 34.4±8.01 years. There was no significant difference in age between groups. Conclusion: The present research showed that levels of Chromium, Iron and Copper in diabetic pregnant women were lower than that of non-diabetic pregnant women; but, these values did not had statistically significant difference. [ABSTRACT FROM AUTHOR]

Copper (Cu) is an essential transition metal ion that acts as a cofactor in many key enzymes. Cu is also needed for several hallmarks of cancer, and many copper-binding proteins are upregulated in various cancers. However, Cu-dependent cellular mechanisms and molecular pathways involved in cancer progression are not known. Fundamental to a better understanding of such phenomena is the investigation of the Cu subcellular distribution in cancer cells. The authors here show that Time-of-Flight Secondary Ion Mass Spectrometry combined with delayed extraction can be successfully applied to probe Cu localization in fixed MDA-MB-231 breast cancer cells providing subcellular resolution. Interestingly, the authors find Cu to be accumulated at nuclear regions of the cancer cells. [ABSTRACT FROM AUTHOR]

Abstract The antioxidant properties and the protective role of organic zinc (Zn) and copper (Cu) in white blood cells (WBCs) and spermatozoa were analyzed through quantification of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 4 (GPx4) and nuclear factor erythroid 2-like 2 (NFE2L2) and correlations were determined with sperm functional characteristics in Osmanabadi bucks. Bucks (aged 5 months; n = 40) were divided into ten groups, and the dietary treatments comprised of a control and nine treatment groups as follows: organic Zn as Zn 20, Zn 40 and Zn 60, organic Cu as Cu 12.5, Cu 25, Cu 37.5 and combined organic Zn and Cu as Zn 20+Cu 12.5, Zn 40+Cu 25, Zn 60+Cu 37.5, respectively per kg dry matter for a period of 8 months. The blood (120 and 240 days) and semen (240 days: 40 × 4 = 160) samples were collected from 40 bucks. In WBCs: the relative abundance of mRNA for SOD1, CAT, GPx4, NFE2L2 was greater (P < 0.05) in (120 and 240 days) in majority of the mineral supplemented animals. In spermatozoa: the relative abundance of SOD1, NFE2L2, GPx4 and CAT mRNA was greater (P < 0.05) in selected treatment groups. The abundance of SOD1 mRNA in WBCs was positively correlated (P < 0.05) with sperm mass motility (r = 0.692, P = 0.027). The abundance of GPx4 mRNA was negatively correlated (P < 0.05) with type A sperm (straightness; STR) > 85% and amplitude of lateral head displacement (ALH) > 2.5 μm/ s) (r = −0.711, P = 0.021) and (P < 0.05) positively correlated with sperm viability (r = 0.669, P = 0.035). Organic Zn and Cu supplementation was associated with an increase in the expression of antioxidant defense enzyme genes in bucks. [ABSTRACT FROM AUTHOR]

Essential metals are vital elements for human biology. Iron, copper, and zinc are all essential for life. Trace metal dyshomeostasis has been linked to cognitive deterioration and in particular to a disturbance in the regulation of copper (Cu), characterized by an increase in serum Cu not bound to ceruloplasmin (nCp-Cu also known as “free” copper). It is thought to play a role in the development of Alzheimer’s disease (AD), the most common form of dementia. Copper homeostasis is finely regulated in our bodies and the expansion of exchangeable nCp-Cu is symptom of the breakdown of this homeostasis, which affects myriad biological pathways. If not structurally bound to enzymes or coordinated by proteins, copper generates free radicals via Haber-Weiss and Fenton reactions. Human Serum Albumin (HSA) is the most abundant serum protein and the main protein exchanging copper in the nCp-Cu pool. Copper coordinated by HSA is in equilibrium with copper coordinated by other small copper chelators circulating in the blood stream in a dynamic and exchangeable manner dependent on environmental osmolarity, oxidation state, pH and compounds’ functions. Albumin is susceptible to glycation starting from Maillard reaction, carbohydrates, in particular glucose, form advanced glycation end-products (AGEs). AGE-albumin is one of this products. Free radicals and free metals in circulation accelerate this cross-linking of protein with carbohydrates. Modified albumins are also significantly less effective than native forms in avoiding the aggregation of Aβ, the main component of the amyloid plaques in the AD brain. The current review aims to provide insight into the coordination chemistry of copper in plasma with a special glance toward the exchangeable copper coordinated by albumin, to explore how aberrant regulations of this interaction are linked to the aetiology of AD. [ABSTRACT FROM AUTHOR]

Although iron and copper are co-ordinately regulated in living cells, the homeostatic effects of each of these metals on the other remain unknown. Here, we show the function of AfMac1, a transcriptional activator of the copper and iron regulons of Aspergillus fumigatus, on the interaction between iron and copper. In addition to the copper-specific AfMac1-binding motif 50-TGTGCTCA-30 found in the promoter region of ctrC, the ironspecific AfMac1-binding motif 50-AT(C/G)NN(A/T)T(A/C)-30 was identified in the iron regulon but not in the copper regulon by ChIP sequence analysis. Furthermore, mutation of the AfMac1-binding motif of sit1 eliminated AfMac1-mediated sit1 up-regulation. Interestingly, the regulation of gene expression in the iron regulon by AfMac1 was not affected by copper and vice versa. AfMac1 localized to the nucleus under iron- or copper-depleted conditions, and AfMac1 was mostly detected in the cytoplasm under iron- or copper-replete conditions. Taken together, these results suggest that A. fumigatus independently regulates iron and copper homeostasis in a manner that involves AfMac1 and mutual interactions. [ABSTRACT FROM AUTHOR]

Thirty-six Sprague Dawley male rats were housed in individual cages and randomly divided into six groups: control, copper sulfate (Cu; 500 ppm body weight (BW)/day), flunixin meglumine (FM; 2.2 ppm BW/day), chrysin (chrysin; 50 ppm BW/day), copper sulfate + FM (Cu + FM; 500 ppm BW/day of copper sulfate and 2.2 ppm BW/day of FM), and copper sulfate + chrysin (Cu + Chrysin; 500 ppm BW/day of copper sulfate and 50 ppm BW/day of chrysin). Feed intake (FI) in the Cu + Chrysin group significantly increased in comparison with that of the Cu group (P < 0.01). Cu excess significantly increased malondialdehyde, indicating oxidative stress. Chrysin and FM administration significantly decreased malondialdehyde levels and increased the superoxide dismutase and catalase activities in the liver and kidney tissues (P < 0.001). Serum TNF-a levels were significantly lower in the Cu + FM and Cu + Chrysin groups in comparison to the Cu group (P < 0.001). It was seen that FM and chrysin treatments alleviated degeneration, necrosis, and apoptosis in the liver and kidney tissues of the Cu-treated rats. Chrysin appeared to ameliorate the adverse effects on FI and liver and kidney tissues by scavenging where the free radicals are located and increasing the activity of antioxidants. [ABSTRACT FROM AUTHOR]

The concentration and distribution of Mg, P, Cl, K, Cu and Zn in the dorsal hippocampus CA1 region of rat brains were studied during memory consolidation and reconsolidation processes stimulated with inhibitory avoidance (IA) tests. Experimental rats were divided into four groups: i) group not submitted to inhibitory avoidance task (IA-N); ii) group submitted to inhibitory avoidance training session (IA-Y); iii) group submitted to inhibitory avoidance reactivation session but did not step down from the platform (IAR-N); and iv) group submitted to avoidance reactivation session and stepped down from the platform (IAR-Y). Elemental concentration and distribution in the CA1 hippocampus region were obtained through the Particle-Induced X-ray Emission (PIXE) technique. The results indicate that the concentration of Mg, P, Cl, K and Cu increased during memory consolidation. During the memory reconsolidation process, the concentrations of Mg, P, Cl and K increased, while Cu and Zn had no significant changes with respect to their basal condition. These results show that the major part of these elements may be engaged in memory consolidation could be also participating in memory reconsolidation. For all elements, the general trend related to their concentration did not change during reconsolidation regardless the presence of a novelty event, i.e. stepping down from the platform. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second leading cause of death among cancer in men. Trace elements are involved in many vital functions. Fluctuations in serum levels of these elements may reflect the occurrence and/or severity of PCa.This prospective case/control study aimed to assess the serum concentration of Cu, Zn and Se in patients with PCa (newly diagnosed and longstanding) and with benign prostatic hyperplasia (BPH). The study recruited 60 patients with PCa (30 newly diagnosed and 30 longstanding patients) and 30 patients with BPH. Other 30 healthy men were randomly selected to be a control group. Sera were separated from blood samples which were collected from each participant. Atomic absorption spectrophotometry was used to measure serum concentration of the studied trace elements. The newly diagnosed patients with PCa showed significantly (P<0.05) higher serum concentration of Cu (3.14±1.1 μg/ml) than each of longstanding group (1.48±0.91 μg/ml), BPH (0.96± 0.17μg/ml), and controls (1.1±0.23 μg/ml), while there were no significant differences between different groups regarding Zn concentration. In newly diagnosed patients, Se concentration was 58.2± 6.12 ng/ml) which is significantly lower than other groups (P<0.05). In longstanding patients, the concentration was relatively high (98.4± 12.38 ng/ml) and differed significantly from patients with BPH (72.4± 8.11 ng/ml) and non-significantly from controls (108.1±15.34 ng/ml) These results indicate that serum levels of Cu and Se undergo a marked change in newly diagnosed patients with PCa, and thus could be used as additional marker for this malignancy. [ABSTRACT FROM AUTHOR]

Copper (Cu) plays an essential role in the human and animal body system. One of the most important sources of Cu is milk. The purpose of this study was to determine the effect of different doses of injection of inorganic Cu and organic Cu as Cu-arginine and Cu-lysine on Cu concentrations of milk in the lactating Zandi's ewes. This experimental research involved 54 lactating Zandi's ewes collected from the department of State Organization Agriculture of Tehran province, Iran. They were allocated into three main groups included: group 1) which received inorganic form of Cu as copper chloride, groups 2 and 3) which received organic Cu as Cu-arginine or Cu-lysine (25, 50 and 100 mg kg-1 of body weight (BW)) in the chelate form, respectively. The milk samples were taken 30 min before and 6 hours after intravenous injection of Cu preparations. The Cu concentration in milk was measured using the flame atomic absorption spectrometric method. There was no significant difference among the groups in milk's Cu concentration before administration of either inorganic or organic Cu. Data analysis showed that the administration of inorganic Cu caused a significant increase (P<0.01) of Cu concentration in the milk in a dose dependent manner. Furthermore, the administration of Cu-arginine or Cu-lysine in chelate form caused a significant increase (P<0.01) in milk Cu concentration compared to the inorganic Cu. In conclusion, administration of different forms of Cu influenced the Cu concentration in the milk. The organic forms of Cu led to a significant increase in milk Cu concentration in a dose dependent manner compared to the inorganic form of Cu. [ABSTRACT FROM AUTHOR]

Summary: The ability of the human fungal pathogen Cryptococcus neoformans to adapt to variable copper (Cu) environments within the host is key for successful dissemination and colonization. During pulmonary infection, host alveolar macrophages compartmentalize Cu into the phagosome and C. neoformans Cu‐detoxifying metallothioneins, MT1 and MT2, are required for survival of the pathogen. In contrast, during brain colonization the C. neoformans Cu+ importers Ctr1 and Ctr4 are required for virulence. Central for the regulation and expression of both the Cu detoxifying MT1/2 and the Cu acquisition Ctr1/4 proteins is the Cu‐metalloregulatory transcription factor Cuf1, an established C. neoformans virulence factor. Due to the importance of the distinct C. neoformans Cu homeostasis mechanisms during host colonization and virulence, and to the central role of Cuf1 in regulating Cu homeostasis, we performed a combination of RNA‐Seq and ChIP‐Seq experiments to identify differentially transcribed genes between conditions of high and low Cu. We demonstrate that the transcriptional regulation exerted by Cuf1 is intrinsically complex and that Cuf1 also functions as a transcriptional repressor. The Cu‐ and Cuf1‐dependent regulon in C. neoformans reveals new adaptive mechanisms for Cu homeostasis in this pathogenic fungus and identifies potential new pathogen‐specific targets for therapeutic intervention in fungal infections. [ABSTRACT FROM AUTHOR]

Wilson disease is a rare but important disorder of copper metabolism, with a failure to excrete copper appropriately into bile. It is a multisystem condition with presentations across all branches of medicine. Diagnosis can be difficult and requires a high index of suspicion. It should be considered in unexplained liver disease particularly where neuropsychiatric features are also present. Treatments are available for all stages of disease. A particularly important presentation not to overlook is acute liver failure which carries a high mortality risk and may require urgent liver transplantation. Here, we provide an overview of this complex condition. [ABSTRACT FROM AUTHOR]

The clinical course after ischemic stroke can vary considerably despite similar lesions and clinical status at the onset of symptoms, suggesting that individual factors modulate clinical recovery. Here, we sought to test the working hypothesis that elevated copper values provide prognostic information, and specifically predict worse clinical recovery. We further sought to support previous findings regarding metal metabolism in acute stroke. We assessed total antioxidant status, oxidative stress factors (peroxides) and metal metabolism markers (iron, copper, ceruloplasmin concentration and activity, ferritin, and transferrin) in the acute phase (2-10 days from symptom onset) in 30 patients affected by unilateral middle cerebral artery (MCA) stroke. A longitudinal assessment of clinical deficit was performed in the acute and stabilized phases (typically 6 months post-stroke) using the National Institutes of Health Stroke Scale (NIHSS). In identifying recovery-related factors, we considered effective recovery (ER), calculated as the ratio between actual NIHSS recovery and the total potential recovery. This allows an estimation of the actual recovery adjusted for the patient's initial condition. In the acute phase, clinical severity was correlated with increased peroxide concentrations, and lower iron levels. Less successful clinical recovery was correlated with increased acute copper levels, which entered a multiple regression model that explained 24% of ER variance. These pilot data suggest that, in the acute phase of an ischemic stroke, copper may provide useful information about clinical recovery. [ABSTRACT FROM AUTHOR]

Meta-analyses show copper dyshomeostasis in Alzheimer's disease. However, a study evaluating copper changes in other neurodegenerative forms of dementia has not yet been performed. In this study, we assessed copper, ceruloplasmin, copper not bound to ceruloplasmin, and copper to ceruloplasmin ratio in 85 patients affected by frontotemporal lobar degeneration (FTLD) and 55 healthy controls. Data were analyzed through multivariate ANOVA models taking into account age and sex as covariates and the stratification for FTLD variants, after calculating power analysis to ensure the reliability of the conclusions drawn. The study revealed no difference between the groups. [ABSTRACT FROM AUTHOR]

Although many studies have been carried out in order to understand the implication of copper (Cu) in the pathogenesis of multiple sclerosis (MS), the exact role that this metal plays in the disease is not still clear. Because of the lack of information in this subject, the present study compared the serum and cerebrospinal (CSF) levels of copper in MS patients in respect to a control group, matched for age and sex, finding a significant increase of metal concentrations, in both biological fluids of MS subjects. To confirm the possible impairment of Cu metabolism, we analyzed ceruloplasmin (Cp) level and activity, seeing as this protein is an established peripheral marker in diseases associated with Cu imbalance. By comparing these two parameters between control and MS subjects, we found an increase of Cp levels, associated with a decrease in Cp activity, in the second group. By analysing these data, free copper levels were calculated, significantly increased in serum of MS subjects; the increase in free copper could be one of the predisposing factors responsible for the Cu altered levels in CSF of MS patients. At the same time, this alteration could be attributable to the inability to incorporate Cu by Cp, probably due to the high oxidative environment found in serum of MS patients. Overall, all these copper alterations may play a role in MS pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction: zinc (Zn) and copper (Cu) are essential elements that play an important role in the whole-body metabolism and seems to have a role in the pathogenesis of the liver cirrhosis (LC).Objective: the aim of this study is to evaluate the influence on serum Zn and Cu concentrations and Cu/Zn ratios of different factors like cirrhosis, severity index, age, sex, death, and disease complications.Methods: ninety-three patients with LC were included. The severity index was measured by the Child-Pugh index (CPI).Results: mean serum Cu concentration and Cu/Zn ratio were significantly higher in patients than in healthy controls (p ≤ 0.001). Serum Zn concentrations were reduced with higher cirrhosis severity (specifically low vsmedium severity CPI, p < 0.05). Mean serum Cu concentration was significantly higher in the oldest (> 50 years) versusyoungest (< 30 years) age group. Serum Zn concentrations were lower and Cu/Zn ratios were higher (p < 0.05) in patients that died. Among complications, significantly higher serum Zn concentrations were found in cirrhotic patients with ascites than in those with bacteremia-sepsis.Conclusions: levels of Zn, Cu and Cu/Zn ratio are affected by the presence of hepatic cirrhosis. Serum Zn concentrations are lower with higher severity of cirrhosis, while those for Cu are increased in cirrhotic patients. We can observe that the presence of elevated Cu/Zn ratios in these patients might be useful in the evaluation of suspected liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Micronutrients may influence the development and differentiation of sperm cells. The aim of this study was to assess the possible association of deficiencies in several vitamins and trace elements with sperm abnormalities in men with obesity.Participants and Methods: Thirty male patients with moderate to severe obesity and ten lean controls who gave written informed consent were included. Anthropometric parameters were recorded. Hormonal and lipid profiles were analyzed, as well as serum concentrations of zinc, copper, retinol, α-tocopherol, 25-hydroxyvitamin D, cobalamin, and folic acid. For sperm analysis, we used the reference values proposed by the World Health Organization.Results: Fourteen of the thirty men (47%) presented abnormal sperm results. The most common abnormality was low motility in 33% of them, followed by low sperm concentration in 27% of the patients. Patients with abnormal sperm results showed lower serum folic acid (p = 0.005) and higher serum estradiol (p = 0.015) and copper (p = 0.033) than lean controls. The ejaculate volume inversely correlated with body mass index (BMI; r = -0.378, p = 0.016) and serum estradiol (r = -0.328, p = 0.041). Total number of sperm correlated inversely with BMI (r = -0.428, p = 0.006) and serum estradiol (r = -0.507, p = 0.001) and positively with serum folic acid (r = 0.356, p = 0.026) and retinol (r = 0.421, p = 0.009). Total motility of sperm inversely correlated with BMI (r = -0.433, p = 0.005), serum estradiol (r = -0.475, p = 0.002), and copper (r = -0.416, p = 0.012) and positively correlated with serum folic acid (r = 0.522, p = 0.001) and retinol (r = 0.350, p = 0.034).Conclusions: Sperm abnormalities in men with obesity are associated with excess body weight and micronutrient concentrations. [ABSTRACT FROM AUTHOR]

A family of terbium probes was synthesized and evaluated for the luminescence detection of copper and zinc in water at neutral pH. Each probe incorporates a terbium ion chelated by a macrocyclic polyaminocarboxylate and conjugated to either one, two, or three phenanthridine antennas via a diamine linker. All three probes, Tb-1Phen, Tb-2Phen, and Tb-3Phen, exhibit similar responses toward copper and zinc. In each case, the terbium-centered time-gated phosphorescence decreases upon binding either CuI or CuII but not upon addition of ZnII. The phosphorescence of Tb-2Phen is also not significantly affected by other metal ions including MgII, CaII, MnII, FeII, NiII, CdII, and HgII. Tb-1Phen, on the other hand, responds weakly to MnII, FeII and NiII. The lack of affinity of each probe for ZnII was further confirmed by competition experiments with CuI and CuII. Notably, whereas the terbium-centered emission of each probe is quenched upon copper coordination, the phenanthridine-centered luminescence emission is not. As such, each probe functions as a ratiometric probe for the selective detection of copper over zinc. Theoretical calculations further demonstrate that the turn off response of the probe is due to an increase in the distance separating the lanthanide ion from its phenanthridine antennas upon coordination of copper, which in turn decreases the efficiency of terbium sensitization by the phenanthridines. [ABSTRACT FROM AUTHOR]

Background: vitiligo is a common, acquired, discoloration of the skin, characterized by well circumscribed, ivory or chalky white macules and patches. Researchers suggested that vitiligo may arise from autoimmune (AI), genetic, oxidative stress or neural causes. Zinc (Zn) and copper (Cu) are trace elements that are required in minutely small doses. The unique process of keratinization and melanin formation is enzyme-dependent and therefore could be influenced by trace elements deficiencies or excesses as trace elements are involved in enzymatic activities and immunologic reactions. Aim of work: this study aimed to detect the levels and roles of serum Zn and Cu in the pathogenesis of vitiligo. Patients and methods: our study included 50 vitiligo patients and 50 apparently healthy controls. Age of study groups ranged from 15 to 60 years and both sexes. Serum Zn and Cu levels were measured in each study group. Results: serum Zn levels were statistically significant lower in both the studied groups, but in vitiligo group they were much lower than the control group. Serum Cu levels were statistically insignificant higher in vitiligo group than the control group. Conclusion: there is a relationship between vitiligo and serum Zn. Further studies are needed to obtain better knowledge about effect of the trace elements in vitiligo patients. [ABSTRACT FROM AUTHOR]

Background: Wilson disease (WD) is an inherited neurometabolic disorder that results in excessive copper deposition in the liver and the brain, affecting children and young adults. Without treatment the disease is invariably fatal. Though treatments for WD have been available since the 1950s, the disease continues to be associated with considerable morbidity and mortality because of missed diagnosis, and delayed or inadequate treatment. In this paper we survey WD-related literature in order to review recent advances in WD treatment. Methods: We performed a literature search using the PubMed database for articles relating to WD and its medical treatment. We reviewed the articles, and crossreferences of relevant articles, to summarize the current practices for treatment of WD. Results: The survey shows that if WD is properly treated, in most patients the liver can be stabilized, even severe neurological disability reversed, and patients can resume normal lives. Discussion: Medical treatment for WD includes use of copper chelators (penicillamine, trientine, dimercaprol, dimercaptopropane sulfonate, and ammonium tetrathiomolybdate) and drugs that decrease gastrointestinal copper absorption. Our knowledge of the treatment approaches has benefited from the large systematic clinical studies that have been conducted over the last decade. For each drug used to treat WD, we surveyed its development, indication for use, dosing, efficacy, and adverse effects. [ABSTRACT FROM AUTHOR]

Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. Methods: We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. Results: The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9 ± 2.41 vs. 11.2 ± 3.36 μmol/L, p < 0.001). There was a positive correlation between serum γ-GGT activity and copper in all eligible subjects (r = 0.198, p = 0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r = 0.322, p < 0.001; r = 0.230, p = 0.010). The results of multiple linear regression analysis showed that serum γ-GGT maintained a significantly positive correlation with copper after adjusting for multiple potential confounders (b = 0.464, p = 0.001). Conclusions: This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population. [ABSTRACT FROM AUTHOR]

In this paper, we report the inactivation of copper containing bovine plasma amine oxidase (BPAO) by a series of saturated alkylamines containing halogen atoms at γ-position, which are 1,1,1-trihalo-3-aminopropane, 1,1,1-trifluoro-2-hydroxy-3-aminopropane, 1,1,1-trichloro-2-hydroxy-3-aminopropane, and 1,1,1-trichloro-2-(2-phenethyloxy)-3-aminopropane . The trihalo-2-hydroxypropylamine analogs exhibited a time-dependent inactivation behavior of BPAO, with 1,1,1-trifluoro-2-hydroxy-3-aminopropane as the most efficient inactivator. The incorporation of a OH group at β-position increased inactivation efficiency by 10-fold within the trifluoro analogs, and the incorporation of a phenethyloxy group at β-position exhibited a higher efficiency by 3-fold within the trichloro analogs based on I 75 values. All four compounds were found to be irreversible inactivators for BPAO. [ABSTRACT FROM AUTHOR]

The nano copper has been widely used in modern clinical medicine practice. However, it has been noticed that nano copper particles induce cell injury and toxicity. The present study was designed to determine the effect of nano copper particles on cell injury of intestinal epithelial cells (IECs) in piglets. The IECs were treated with different doses of nano copper (5, 10, 20 and 40 μg/ml) for 24–48 h to observe cell injury and toxicity. Cell injury was measured based on morphological and other changes including oxidative stress and genes expression. The oxidative stress markers were assayed by differential expression levels of SOD, MDA and Metallothionein (MT) in addition to CTR1, SOD1, COX17, MT and ATOX1 genes expression. Cellular morphology showed an increasing growth of cells without nano copper treatment and nano copper showed significant damage to IECs with higher dose as compared to low dose. Higher doses of copper nanoparticles (10, 20 and 40 μg/ml) have membrane damaging effect on the intestinal epithelial cells, whereas MDA contents and MT value were significantly increased, and SOD activity was decreased with the increase in concentration of nanoparticles. Nano copper up-regulated the CTR1 and SOD1 genes and down-regulated the relative expression of COX17, MT and ATOX1 genes significantly in a dose-dependent manner. The findings of the current study provide important insights that nano copper plays an important role in intestinal epithelial cell injury and oxidative stress. [ABSTRACT FROM AUTHOR]

In this speculative examination, main focused is to address Cu-nanoparticles application in an inclined stenosed elastic artery with balloon model examination. Flow of blood in an inclined stenotic artery is investigated mathematically by considering its behavior as viscous fluid. The dimensionless terms of temperature, velocity, resistance to blood flow and stress on wall of stenotic inclined artery has been computed by using mild stenosis approximation. The model is also used to understand the significance of overlapping stenosed artery with tapered angle and inclination angle. At the end, the results confirmed that the impulsion of copper as drug agent minimized the amplitude of the resistance to blood flow and hence nanoparticles plays an important role in engineering as well in biomedical applications. [ABSTRACT FROM AUTHOR]

The primary objective of the present study was to investigate the levels of essential trace elements in hair and serum in children with autism spectrum disorder (ASD) and investigate the age and gender effects. Children with ASD were characterized by significantly higher levels of copper (Cu) (+8%), iron (Fe) (+5%), and selenium (Se) (+13%) levels in hair and only 8% higher serum Cu levels. After stratification for gender, ASD boys were characterized by significantly increased hair Cu (+ 25%), Fe (+ 25%), and Se (+ 9%) levels, whereas in girls only Se content was elevated (+ 15%). Boys and girls suffering from ASD were characterized by significantly higher serum manganese (Mn) (+20%) and Cu (+18%) as compared to the control values, respectively. In the group of younger children (2-5 years), no significant group difference in hair trace element levels was detected, whereas serum Cu levels were significantly higher (+7%). In turn, the serum concentration of Se in ASD children was 11% lower than that in neurotypical children. In the group of older children with ASD (6-10 years), hair Fe and Se levels were 21% and 16% higher, whereas in serum only Cu levels were increased (+12%) as compared to the controls. Correlation analysis also revealed a different relationship between serum and hair trace element levels with respect to gender and age. Therefore, it is highly recommended to assess several bioindicative matrices for critical evaluation of trace element status in patients with ASD in order to develop adequate personalized nutritional correction. [ABSTRACT FROM AUTHOR]

Copper(ii) ion mediated C–H oxidation of dipyrromethanes (DPMs) to the corresponding dipyrrins followed by complexation invoked the selective sensing of copper(ii) ions in aqueous solutions. On the addition of copper, the colour of the DPM solution instantaneously changes from yellow to pink with the detection limit of 0.104 μM measured by absorption spectroscopy, whereas visible colour changes could be observed by the naked eye for concentrations as low as 3 μM. [ABSTRACT FROM AUTHOR]

Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was deployed for quantitative mapping of the Cu distribution in cryo-sections of liver tissue from mice with cholestatic liver disease induced via common bile duct ligation (CBDL). Cu distribution maps of the liver sections were obtained from the CBDL-operated mice sacrificed at different time points (2, 4 and 6 weeks) after the surgical intervention and compared with those of the corresponding control (sham-operated) mice. Cu quantification was accomplished versus matrix-matched thin sections of spiked liver tissue homogenates and versus spiked gelatin droplet standards. No statistical differences were obtained between the results using the two calibration approaches and thus, both were considered suitable for quantitative Cu bioimaging of liver cryo-sections. On the basis of practical considerations, i.e. simplicity, low cost and availability of the material, spiked gelatin droplet standards are the preferred choice for quantitative determination of the Cu distribution in liver tissue cryo-sections. An inhomogeneous hepatic Cu distribution was observed in the CBDL mice, in contrast to the homogeneous hepatic Cu distribution established for the sham-operated mice. The Cu levels increased with the progression of the disease and a strong accumulation was observed in some necrotic areas. High-resolution LA-ICP-MS bioimaging, using a circular spot size of 2 μm, was suitable for the visualization of the Cu distribution in liver tissue on a (sub-)cellular level. In addition to the quantitative Cu mapping, the spatial distribution of Zn was also monitored in the liver cryo-sections of the control and the 2, 4 and 6 week CBDL mice, but in all cases, Zn was homogeneously distributed across the tissue. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate serum level of copper, zinc, iron and metabolic parameters in postmenopausal women with diabetes. A total of 413 postmenopausal women were enrolled in the current study. Women were divided into 4 groups with equal age and body mass index according to glycated hemoglobin (HbA 1c ) levels (≤5.5; 5.5–6.0; 6.0–6.5; >6.5%). Serum Fe, Cu, and Zn levels were assessed using inductively-coupled plasma mass-spectrometry. Blood HbA 1c , serum glucose, insulin, C-reactive protein (CRP), ferritin, and ceruloplasmin (Cp) were assessed using commercial kits. Homeostatic model assessment insulin resistance (HOMA-IR) and transferrin (Tf) saturation were calculated. The obtained data demonstrate that every 0.5% increase in HbA 1c levels from 5.5% is associated with a significant elevation of glucose, insulin, CRP, and HOMA-IR values. Diabetic patients were characterized by significantly higher Fe (11%), Cu (8%), and Zn (6%) levels as compared to the controls. At the same time, the overall trend to increased metal levels in association with HbA 1c was detected only for Fe (p < 0.05) and Cu (p < 0.05). Serum ferritin levels in diabetic women was 3-fold higher than in the controls, whereas Tf saturation was decreased by 35%. Serum Cp levels were significantly increased by 19% in prediabetes, whereas in diabetic postmenopausal women no such increase was observed. A significant elevation of total metal concentration in diabetic subjects without a concomitant elevation of transport proteins may be indicative of increased levels of “free” Fe and Cu, known to be toxic. [ABSTRACT FROM AUTHOR]

Zinc and copper are essential trace elements. Dyshomeostasis in these two metals has been observed in Alzheimer’s disease, which causes profound cognitive impairment. Insulin therapy has been shown to enhance cognitive performance; however, recent data suggest that this effect may be at least in part due to the inclusion of zinc in the insulin formulation used. Zinc plays a key role in regulation of neuronal glutamate signaling, suggesting a possible link between zinc and memory processes. Consistent with this, zinc deficiency causes cognitive impairments in children. The effect of zinc supplementation on short- and long-term recognition memory, and on spatial working memory, was explored in young and adult male Sprague Dawley rats. After behavioral testing, hippocampal and plasma zinc and copper were measured. Age increased hippocampal zinc and copper, as well as plasma copper, and decreased plasma zinc. An interaction between age and treatment affecting plasma copper was also found, with zinc supplementation reversing elevated plasma copper concentration in adult rats. Zinc supplementation enhanced cognitive performance across tasks. These data support zinc as a plausible therapeutic intervention to ameliorate cognitive impairment in disorders characterized by alterations in zinc and copper, such as Alzheimer’s disease. [ABSTRACT FROM AUTHOR]