Botanicals and Phosphonate Show Potential to Replace Copper for Control of Potato Late Blight

PubMed Central

Forrer, Hans-Rudolf

2017-01-01

Potato late blight (PLB) caused by Phytophthora infestans (Pi) is the most harmful disease in potato production worldwide. In organic farming, copper is used despite its persistence in soil and toxicity to soil organisms. To replace copper, suspensions of powders from three promising botanicals, including bark of buckthorn (Frangula alnus, FA), roots of medicinal rhubarb (Rheum palmatum) and galls of the nutgall tree (Galla chinensis), were tested in multi-year field experiments. The current study shows for the first time that botanicals could replace copper under field conditions and best PLB reduction on leaves was achieved with FA, reaching a level close to that of 2 to 3 kg copper per hectare and year. Better results than with copper were achieved with Phosfik® (Ph), a phosphonate-based product. For both FA and Ph, the mode of action is based on induced resistance, for Ph also on direct fungicidal effects. A disadvantage of Ph is the accumulation of residues in potato tubers. Nevertheless, two to three applications with 2 to 3 L/ha of Ph would be feasible to not exceed a minimal risk level (MLR) of 20 mg/kg of phosphorous acid as proposed by the European Food Safety Authority. Due to an excellent environmental profile and a complex mode of action counteracting Pi resistance, phosphonate-based products would be most suitable for sustainable PLB management in integrated pest management (IPM) programmes. PMID:29371580

Effect of copper on the scope for growth of clams (Tapes philippinarum) from a farming area in the Northern Adriatic Sea.

PubMed

Munari, Cristina; Mistri, Michele

2007-09-01

Copper is currently the most common biocide in antifouling paints. Levels of this metal were measured in the water, particulate matter and sediments from a shellfish farming area in the Sacca di Goro (Northern Adriatic Sea) over one year. With respect to the 1980s, copper environmental level increased twofold. The release of copper from shellfish farmers' boats was also estimated to be > 250 kg Cu y(-1). Clams Tapes philippinarum were collected in the same area and seasonally exposed to a sublethal (10 microg Cu l(-1)) concentration of copper. Physiological traits were significantly affected by copper exposure (scope for growth declined as a result of reduced clearance rate, increased oxygen consumption and a generally lower absorption efficiency). The results of this study are cause for concern for shellfish farming activities at least in Northern Adriatic, where shellfish farming is a monoculture of T. philippinarum. A strict interpretation of the precautionary principle might suggest that more rigorous regulatory action to control copper inputs in the field would be justified.

Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

PubMed

Stepien, Magdalena; Jenab, Mazda; Freisling, Heinz; Becker, Niels-Peter; Czuban, Magdalena; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Mancini, Francesca Romana; Savoye, Isabelle; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Iqbal, Khalid; Trichopoulou, Antonia; Bamia, Christina; Orfanos, Philippos; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Naccarati, Alessio; Panico, Salvatore; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; Merino, Susana; Jakszyn, Paula; Sanchez, Maria-Jose; Dorronsoro, Miren; Huerta, José María; Barricarte, Aurelio; Boden, Stina; van Guelpen, Behany; Wareham, Nick; Khaw, Kay-Tee; Bradbury, Kathryn E; Cross, Amanda J; Schomburg, Lutz; Hughes, David J

2017-07-01

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Catalytic therapy of cancer by ascorbic acid involves redox cycling of exogenous/endogenous copper ions and generation of reactive oxygen species.

PubMed

Hadi, S M; Ullah, M F; Shamim, U; Bhatt, S H; Azmi, A S

2010-01-01

Catalytic therapy is a cancer treatment modality based on the generation of reactive oxygen species (ROS) through administration of ascorbate/medicinal herbal extracts and copper. It is known that antioxidants such as ascorbate also exhibit prooxidant activity in the presence of transition metals such as copper. Based on our work and that in the literature, in this review we propose a mechanism for the cytotoxic action of ascorbate against cancer cells. It involves redox cycling of exogenous/endogenous copper ions and the consequent generation of ROS leading to oxidative DNA breakage. Using human peripheral lymphocytes and the Comet assay, we have shown that ascorbic acid is able to cause oxidative breakage in cellular DNA. Such DNA degradation is inhibited by neocuproine (a Cu(I) sequestering agent) and scavengers of ROS indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. Similar results are also obtained with plant polyphenol antioxidants that are important constituents of medicinal herbal extracts. Copper is an essential component of chromatin and can take part in redox reactions. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and ascorbate/plant polyphenols to generate ROS. In this review we cite evidence to indicate that in catalytic therapy cytotoxic action against cancer cells involves redox cycling of exogenous/endogenous copper ions. Copyright © 2010 S. Karger AG, Basel.

The National Shipbuilding Research Program. Analysis of Wash Water Treatment Efficiency for Copper and Zinc

DTIC Science & Technology

2000-12-15

per trillion for tributyltin (“ TBT ”). This regulatory action lead to an intensive research effort to develop a treatment method for ship’s wash water...antifoulant coating systems, including tributyltin , copper and zinc. In 1997 The Commonwealth of Virginia established an effluent discharge limit of 50 parts...waste stream that could consistently remove TBT to levels below this discharge standard. This work is currently being performed by the Center for

Micro determination of plasma and erythrocyte copper by atomic absorption spectrophotometry

PubMed Central

Blomfield, Jeanette; Macmahon, R. A.

1969-01-01

The free and total plasma copper and total erythrocyte copper levels have been determined by simple, yet sensitive and highly specific methods, using atomic absorption spectrophotometry. For total copper determination, the copper was split from its protein combination in plasma or red cells by the action of hydrochloric acid at room temperature. The liberated copper was chelated by ammonium pyrrolidine dithiocarbamate and extracted into n-butyl acetate by shaking and the organic extract was aspirated into the atomic absorption spectrophotometer flame. The entire procedure was carried out in polypropylene centrifuge tubes, capped during shaking. For the free plasma copper measurement the hydrochloric acid step was omitted. Removal of the plasma or erythrocyte proteins was found to be unnecessary, and, in addition, the presence of trichloracetic acid caused an appreciable lowering of absorption. Using a double-beam atomic absorption spectrophotometer and scale expansion × 10, micro methods have been derived for determining the total copper of plasma or erythrocytes with 0·1 ml of sample, and the free copper of plasma with 0·5 ml. The macro plasma copper method requires 2 ml of plasma and is suitable for use with single-beam atomic absorption spectrophotometers. With blood from 50 blood donors, normal ranges of plasma and erythrocyte copper have been determined. PMID:5776543

Copper and Antibiotics: Discovery, Modes of Action, and Opportunities for Medicinal Applications.

PubMed

Dalecki, Alex G; Crawford, Cameron L; Wolschendorf, Frank

2017-01-01

Copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. However, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including DNA, lipids, and proteins. To restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copper to minimize its deleterious effects. This weakness is actively exploited by phagocytes, which utilize a copper burst to destroy pathogens. Though administration of free copper is an unreasonable therapeutic antimicrobial itself, due to insufficient selectivity between host and pathogen, small-molecule ligands may provide an opportunity for therapeutic mimicry of the immune system. By modulating cellular entry, complex stability, resistance evasion, and target selectivity, ligand/metal coordination complexes can synergistically result in high levels of antibacterial activity. Several established therapeutic drugs, such as disulfiram and pyrithione, display remarkable copper-dependent inhibitory activity. These findings have led to development of new drug discovery techniques, using copper ions as the focal point. High-throughput screens for copper-dependent inhibitors against Mycobacterium tuberculosis and Staphylococcus aureus uncovered several new compounds, including a new class of inhibitors, the NNSNs. In this review, we highlight the microbial biology of copper, its antibacterial activities, and mechanisms to discover new inhibitors that synergize with copper. © 2017 Elsevier Ltd. All rights reserved.

Concentrations of cadmium and selected essential elements in malignant large intestine tissue

PubMed Central

Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

2015-01-01

Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

Importance of Pipe Deposits to Lead and Copper Rule Compliance

EPA Science Inventory

When Madison, WI exceeded the lead Action Level in 1992, residential and off-line tests suggested that lead release into the water was more complex than a simple lead solubility mechanism. In-depth scale analyses (color/texture, mineralogical and elemental composition) of 5 excav...

PREDICTING LEAD DISSOLUTION IN DRINKING WATER DISTRIBUTION SYSTEMS: EFFECT OF FLUORIDE ADDITIVES ON LEAD SOLUBILITY AND CORROSION

EPA Science Inventory

Many water systems have encountered difficulties in meeting the action levels established by the Lead and Copper Rule. Several chemical parameters contribute to the corrosion of lead plumbing and may influence the nature of the passivating films formed on distribution materials....

40 CFR 141.84 - Lead service line replacement requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Lead service line replacement... PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Control of Lead and Copper § 141.84 Lead service line replacement requirements. (a) Systems that fail to meet the lead action level in tap samples...

40 CFR 141.84 - Lead service line replacement requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Lead service line replacement... PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Control of Lead and Copper § 141.84 Lead service line replacement requirements. (a) Systems that fail to meet the lead action level in tap samples...

40 CFR 141.84 - Lead service line replacement requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Lead service line replacement... PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Control of Lead and Copper § 141.84 Lead service line replacement requirements. (a) Systems that fail to meet the lead action level in tap samples...

Impact of DIC, Sulfate and Chloride on Pb(II) Solubility

EPA Science Inventory

Corrosion of lead and the subsequent release of lead into drinking water distribution systems pose a concern to public health. Consequently, the U.S. Environmental Protection Agency’s (U.S. EPA) Lead and Copper rule established an action level for lead at the consumer’s tap of 0....

Offpost Interim Response Action, Alternatives Assessment, Version 2.3

DTIC Science & Technology

1988-12-01

copper resulting from the use as algicides or herbicides of basic copper carbonate (molachite), copper sulfate (see below), copper monoethandime, and...mart per million for potable water for residues of -copper resulting from the use as algicides or herbicides of basic copper sulfat. and the other...Water ARAR: 21 C.F.R. § 193.90 (TPFA) -- tolerance of 1 part per million for potable water for residues of copper resulting from the use as algicides or

Reduction of the "burst release" of copper ions from copper-based intrauterine devices by organic inhibitors.

PubMed

Alvarez, Florencia; Schilardi, Patricia L; de Mele, Monica Fernández Lorenzo

2012-01-01

The copper intrauterine device is a contraceptive method that is based on the release of copper ions from a copper wire. Immediately after insertion, the dissolution of copper in the uterine fluid is markedly higher ("burst release") than that necessary for contraception action, leading to a variety of harmful effects. Pretreatments with organic compounds [thiourea (TU) and purine (PU), 10(-4)-10(-2) M concentration range, 1- and 3-h immersion times] were tested. The dissolution of copper with and without pretreatments in TU and PU solutions was analyzed by conventional electrochemical techniques and surface analysis. Pretreatments in PU solutions reduced the initial corrosion rate of copper in simulated uterine solutions, with inhibitory efficiencies that depend on the PU concentration and on the immersion time assayed. Inhibitory efficiency values higher than 98% for pretreatments with ≥10(-3) M PU were found. Conversely, after TU pretreatments, a high copper release was measured. It was concluded that 10(-3) M PU pretreatment is a promising strategy able to reduce the "burst release" of copper and to ensure contraceptive action. Copyright © 2012 Elsevier Inc. All rights reserved.

Emergency contraception review: evidence-based recommendations for clinicians

PubMed Central

Cleland, Kelly; Raymond, Elizabeth G.; Westley, Elizabeth; Trussell, James

2014-01-01

Several options for emergency contraception are available in the United States. This article describes each method, including efficacy, mode of action, safety, side effect profile and availability. The most effective emergency contraceptive is the copper IUD, followed by ulipristal acetate and levonorgestrel pills. Levonorgestrel is available for sale without restrictions, while ulipristal acetate is available with prescription only, and the copper IUD must be inserted by a clinician. Although EC pills have not been shown to reduce pregnancy or abortion rates at the population level, they are an important option for individual women seeking to prevent pregnancy after sex. PMID:25254919

Synthesis of Quaternary Ammonium Salts Based on Diketopyrrolopyrroles Skeletons and Their Applications in Copper Electroplating.

PubMed

Chen, Biao; Xu, Jie; Wang, Limin; Song, Longfeng; Wu, Shengying

2017-03-01

A series of DPP derivatives bearing quaternary ammonium salt centers with different lengths of carbon chains have been designed and synthesized. Their inhibition actions on copper electroplating were first investigated. A total of four diketopyrrolopyrrole (DPP) derivatives showed different inhibition capabilities on copper electroplating. To investigate interactions between metal surface and additives, we used quantum chemical calculations. Static and dynamic surface tension of four DPP derivatives had been measured, and the results showed DPP-10C (1c) with a faster-decreasing rate of dynamic surface tension among the four derivatives, which indicated higher adsorption rate of additive on the cathode surface and gives rise to stronger inhibiting effect of copper electrodeposition. Then, DPP-10C (1c) as the representative additive, was selected for the systematic study of the leveling influence during microvia filling through comprehensive electroplating tests. In addition, field-emission scanning electron microscope images and X-ray diffraction results showed the surface morphology, which indicated that addition of DPP derivative (1c) could lead a fine copper deposit and cause the preferential orientations of copper deposits to change from [220] to [111], which happened in particular at higher concentrations.

Investigation of the Preservation Method within Environmental Protection Agency Method 200.8

EPA Science Inventory

Lead (Pb) is a trace metal that is closely regulated in drinking water systems because of its harmful toxicity. The U.S. Environmental Protection Agency (USEPA) issued the Lead and Copper Rule (LCR), which defines the action level for Lead as 0.015 mg/L. Researchers and drinking ...

Decrease in cytotoxicity of copper-based intrauterine devices (IUD) pretreated with 6-mercaptopurine and pterin as biocompatible corrosion inhibitors.

PubMed

Alvarez, Florencia; Grillo, Claudiaa; Schilardi, Patricial; Rubert, Aldo; Benítez, Guillermo; Lorente, Carolina; de Mele, Mónica Fernández Lorenzo

2013-01-23

The copper intrauterine device (IUD) based its contraceptive action on the release of cupric ions from a copper wire. Immediately after the insertion, a burst release of copper ions occurs, which may be associated to a variety of side effects. 6-Mercaptopurine (6-MP) and pterin (PT) have been proposed as corrosion inhibitors to reduce this harmful release. Pretreatments with 1 × 10(-4) M 6-MP and 1 × 10(-4) M PT solutions with 1h and 3h immersion times were tested. Conventional electrochemical techniques, EDX and XPS analysis, and cytotoxicity assays with HeLa cell line were employed to investigate the corrosion behavior and biocompatibility of copper with and without treatments. Results showed that copper samples treated with PT and 6-MP solutions for 3 and 1 h, respectively, are more biocompatible than those without treatment. Besides, the treatment reduces the burst release effect of copper in simulated uterine solutions during the first week after the insertion. It was concluded that PT and 6-MP treatments are promising strategies able to reduce the side effects related to the "burst release" of copper-based IUD without altering the contraceptive action.

Mineralogical and Molecular Microbial Characterization of a Lead Pipe Removed from a Drinking Water Distribution System

EPA Science Inventory

The U.S. Environmental Protection Agency's (US EPA) Lead and Copper Rule established an action level for lead of 0.0 15 mg/L in a 1 liter first draw sample at the consumer's tap. Lead corrosion and solubility in drinking water distribution systems are largely controlled by the fo...

Mechanisms of Contact-Mediated Killing of Yeast Cells on Dry Metallic Copper Surfaces▿

PubMed Central

Quaranta, Davide; Krans, Travis; Santo, Christophe Espírito; Elowsky, Christian G.; Domaille, Dylan W.; Chang, Christopher J.; Grass, Gregor

2011-01-01

Surfaces made of copper or its alloys have strong antimicrobial properties against a wide variety of microorganisms. However, the molecular mode of action responsible for the antimicrobial efficacy of metallic copper is not known. Here, we show that dry copper surfaces inactivate Candida albicans and Saccharomyces cerevisiae within minutes in a process called contact-mediated killing. Cellular copper ion homeostasis systems influenced the kinetics of contact-mediated killing in both organisms. Deregulated copper ion uptake through a hyperactive S. cerevisiae Ctr1p (ScCtr1p) copper uptake transporter in Saccharomyces resulted in faster inactivation of mutant cells than of wild-type cells. Similarly, lack of the C. albicans Crp1p (CaCrp1p) copper-efflux P-type ATPase or the metallothionein CaCup1p caused more-rapid killing of Candida mutant cells than of wild-type cells. Candida and Saccharomyces took up large quantities of copper ions as soon as they were in contact with copper surfaces, as indicated by inductively coupled plasma mass spectroscopy (ICP-MS) analysis and by the intracellular copper ion-reporting dye coppersensor-1. Exposure to metallic copper did not cause lethality through genotoxicity, deleterious action on a cell's genetic material, as indicated by a mutation assay with Saccharomyces. Instead, toxicity mediated by metallic copper surfaces targeted membranes in both yeast species. With the use of Live/Dead staining, onset of rapid and extensive cytoplasmic membrane damage was observed in cells from copper surfaces. Fluorescence microscopy using the indicator dye DiSBaC2(3) indicated that cell membranes were depolarized. Also, during contact-mediated killing, vacuoles first became enlarged and then disappeared from the cells. Lastly, in metallic copper-stressed yeasts, oxidative stress in the cytoplasm and in mitochondria was elevated. PMID:21097600

Modification of surface layers of copper under the action of the volumetric discharge initiated by an avalanche electron beam in nitrogen and CO2 at atmospheric pressure

NASA Astrophysics Data System (ADS)

Shulepov, M. A.; Akhmadeev, Yu. Kh.; Tarasenko, V. F.; Kolubaeva, Yu. A.; Krysina, O. V.; Kostyrya, I. D.

2011-05-01

The results of experimental investigations of the action of the volumetric discharge initiated by an avalanche electron beam on the surface of copper specimens are presented. The volumetric (diffuse) discharge in nitrogen and CO2 at atmospheric pressure was initiated by applying high voltage pulses of nanosecond duration to a tubular foil cathode. It has been found that the treatment of a copper surface by this type of discharge increases the hardness of the surface layer due to oxidation.

77 FR 4275 - Notice of Extension of Public Comment Period for Draft Environmental Impact Statement: Rosemont...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

... Environmental Impact Statement: Rosemont Copper Project AGENCY: Forest Service, USDA. ACTION: Notice of... miles southeast of Tucson, Arizona (Rosemont Copper Project). The U.S. Environmental Protection Agency... Forest Service has decided to accommodate these requests; therefore, comments on the Rosemont Copper...

Copper stress on photosynthesis of black mangle (Avicennia germinans).

PubMed

González-Mendoza, Daniel; Espadas y Gil, Francisco; Escoboza-Garcia, Fernando; Santamaría, Jorge M; Zapata-Perez, Omar

2013-01-01

The effects of copper toxicity on the photosynthetic activities of Avicennia germinans was investigated using two CuSO4 concentrations (0.062 and 0.33 M) added in Hoagland's solution in an aerated hydroponic system. Photosynthesis and chlorophyll fluorescence were measured after 30 h of copper stress. Results obtained in this study show that increasing levels of Cu(+2) of 0.062 and 0.33 M Cu(+2) resulted in a general reduction of the stomatal conductance (28 and 18%, respectively) and 100% of inhibition of net photosynthesis. Additionally, at these concentrations of Cu(+2), reductions of chlorophyll fluorescence parameters were also observed. These changes suggested that the photosynthetic apparatus of Avicennia germinans was the primary target of the Cu(+2) action. It is concluded that Cu(+2) ions causes a drastic decline in photosynthetic gas exchange and Chlorophyll fluorescence parameters in A. germinans leaves.

Some aspects of using ultrasounds to improve sulfurous mineral flotation technology

NASA Technical Reports Server (NTRS)

Mihu, V. P.; Pop, I.

1974-01-01

The results are discussed which were obtained with a new method of desorption of collector reagents connected with improving the selectivity of the flotation of copper and lead concentrate through the action of ultrasounds. Analysis of the results obtained by treating copper and lead concentrate in an ultraacoustic field indicates an increase in the copper content of the copper concentrate, of the lead content in the lead concentrate and, at the same time, a reduction in the lead of the copper concentrate.

Contact killing and antimicrobial properties of copper.

PubMed

Vincent, M; Duval, R E; Hartemann, P; Engels-Deutsch, M

2018-05-01

With the emergence of antibiotic resistance, the interest for antimicrobial agents has recently increased again in public health. Copper was recognized in 2008 by the United States Environmental Protection Agency (EPA) as the first metallic antimicrobial agent. This led to many investigations of the various properties of copper as an antibacterial, antifungal and antiviral agent. This review summarizes the latest findings about 'contact killing', the mechanism of action of copper nanoparticles and the different ways micro-organisms develop resistance to copper. © 2017 The Society for Applied Microbiology.

Copper amplification of prostaglandin E/sub 2/ stimulation of the release of luteinizing hormone-releasing hormone is a postreceptor event

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnea, A.; Cho, G.

1987-01-01

The authors have shown that copper amplifies prostaglandin E/sub 2/ (PGE/sub 2/) 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 PGE/sub 2/ action on the LH-RH neuron, in this study the authors wished to ascertain if copper exerts its effect on the PGE/sub 2/ receptor or on a postreceptor component involved in PGE/sub 2/ action. MEA of adult male rats were incubated for 5 min with 200 ..mu..M Cu/histidine and then incubated for 15 min either with 10 ..mu..M PGE/submore » 2/ (Cu/PGE/sub 2/), 100 ..mu..M forskolin (Cu/forskolin), or 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (Cu/cAMP). Basal release of LH-RH was 4.6 +/- 0.45 pg/15 min per MEA determined by radioimmunoassay. Net stimulated release during the 15-min exposure to PGE/sub 2/, 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/PGE/sub 2/, Cu/forskolin, or Cu/cAMP indicated that copper amplifies the action of PGE/sub 2/ and forskolin but not cAMP action. When MEA were exposed to a mixture of PGE/sub 2/ and forskolin for 15 min, the effects of these two secretagogues on LH-RH release were not additive. In contrast to PGE/sub 2/ and forskolin, copper did not amplify K/sup +/ stimulation of OH-RH release. These results are supportive of the proposition that PGE/sub 2/ stimulation of OH-RH release is mediated by the Ca-cAMP pathway and that copper amplification of PGE/sub 2/ action is a postreceptor event.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leite, Carlos Eduardo, E-mail: carlos.leite@pucrs.br; Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, CEP 90035-003; Maboni, Lucas de Oliveira

The use of zebrafish (Danio rerio) is increasing as an intermediate preclinical model, to prioritize drug candidates for mammalian testing. As the immune system of the zebrafish is quite similar to that of mammals, models of inflammation are being developed for the screening of new drugs. The characterization of these models is crucial for studies that seek for mechanisms of action and specific pharmacological targets. It is well known that copper is a metal that induces damage and cell migration to hair cells of lateral line of zebrafish. Extracellular nucleotides/nucleosides, as ATP and adenosine (ADO), act as endogenous signaling moleculesmore » during tissue damage by exerting effects on inflammatory and immune responses. The present study aimed to characterize the inflammatory status, and to investigate the involvement of the purinergic system in copper-induced inflammation in zebrafish larvae. Fishes of 7 days post-fertilization were exposed to 10 μM of copper for a period of 24 h. The grade of oxidative stress, inflammatory status, copper uptake, the activity and the gene expression of the enzymes responsible for controlling the levels of nucleotides and adenosine were evaluated. Due to the copper accumulation in zebrafish larvae tissues, the damage and oxidative stress were exacerbated over time, resulting in an inflammatory process involving IL-1β, TNF-α, COX-2 and PGE{sub 2}. Within the purinergic system, the mechanisms that control the ADO levels were the most involved, mainly the reactions performed by the isoenzyme ADA 2. In conclusion, our data shed new lights on the mechanisms related to copper-induced inflammation in zebrafish larvae. - Graphical abstract: This scheme provides a chronological proposition for the biochemical events induced by copper in zebrafish larvae. The dashed line shows the absorption of copper over the exposure time. After 1 h of exposure to copper, the release of PGE{sub 2} occurs, followed by an increase of MPO (as a consequence of neutrophil migration), increased expression of genes involved in inflammatory events (IL-1β and TNF-α) and, reduction of the anti-inflammatory cytokine IL-10 at 4 h. At 24 h, the copper concentration is found highly increased, what is coincident with oxidative stress. Regarding the purinergic system, it is possible to observe an inhibition of ecto-5′-NT and ADA, with the consequent increase of AMP and ADA, respectively, at 24 h. The expression of enzyme-related genes shows a decrease in the expression of ecto-5′-NT and variable expressions of ADA subfamily enzymes. - Highlights: • Copper led to increased oxidative stress, and decreased the antioxidants' defenses. • Copper induced time-related changes of IL-1β, TNF-α, IL-10 and PGE{sub 2} levels. • ADA activity controls the levels of adenosine in copper-induced inflammation. • ADA 2 is the main ADA subfamily involved. • The purinergic system seems to be involved in the resolution of inflammation.« less

77 FR 46091 - Notice of Proposed Administrative Settlement Pursuant to the Comprehensive Environmental Response...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

... Copper Mine Site AGENCY: Environmental Protection Agency. ACTION: Notice, request for public comments... concerning the ANACONDA COPPER MINE SITE (the ``Site''), located in Yerington, Lyon County, Nevada. The... Peak Services Agreement for the Anaconda Copper Mine Site, and Region IX Docket No. 9-2012-07. FOR...

Nonlinear damage analysis: Postulate and evaluation

NASA Technical Reports Server (NTRS)

Leis, B. N.; Forte, T. P.

1983-01-01

The objective of this program is to assess the viability of a damage postulate which asserts that the fatigue resistance curve of a metal is history dependent due to inelastic action. The study focusses on OFE copper because this simple model material accentuates the inelastic action central to the damage postulate. Data relevant to damage evolution and crack initiation are developed via a study of surface topography. The effects of surface layer residual stresses are explored via comparative testing as were the effects in initial prestraining. The results of the study very clearly show the deformation history dependence of the fatigue resistance of OFE copper. Furthermore the concept of deformation history dependence is shown to qualitatively explain the fatigue resistance of all histories considered. Likewise quantitative predictions for block cycle histories are found to accurately track the observed results. In this respect the assertion that damage per cycle for a given level of the damage parameter is deformation history dependent appears to be physically justified.

Different roles of glutathione in copper and zinc chelation in Brassica napus roots.

PubMed

Zlobin, Ilya E; Kartashov, Alexander V; Shpakovski, George V

2017-09-01

We investigated the specific features of copper and zinc excess action on the roots of canola (Brassica napus L.) plants. Copper rapidly accumulated in canola root cells and reached saturation during several hours of treatment, whereas the root zinc content increased relatively slowly. Excessive copper and zinc entry inside the cell resulted in significant cell damage, as evidenced by alterations in plasmalemma permeability and decreases in cellular enzymatic activity. Zinc excess specifically damaged root hair cells, which correlated with a pronounced elevation of their labile zinc level. In vitro, we showed that reduced glutathione (GSH) readily reacted with copper ions to form complexes with blocked sulfhydryl groups. In contrast, zinc ions were ineffective as glutathione blockers, and glutathione molecules did not lose their specific chemical activity in the presence of Zn 2+ ions. The effect of copper and zinc excess on the glutathione pool in canola root cells was analysed by a combination of biochemical determination of total and oxidized glutathione contents and fluorescent staining of free reduced glutathione with monochlorobimane dye. Excess copper led to dose-dependent diminution of free reduced glutathione contents in the root cells, which could not be explained by the loss of total cellular glutathione or its oxidation. In contrast, we observed little effect of much higher intracellular zinc concentrations on the free reduced glutathione content. We concluded that GSH plays an important role in copper excess, but not zinc excess chelation, in canola root cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

SLC31 (CTR) Family of Copper Transporters in Health and Disease

PubMed Central

Kim, Heejeong; Wu, Xiaobin; Lee, Jaekwon

2012-01-01

Copper is a vital mineral for many organisms, yet it is highly toxic as demonstrated by serious health concerns associated with its deficiency or excess accumulation. The SLC31 (CTR) family of copper transporters is a major gateway of copper acquisition in eukaryotes, ranging from yeast to humans. Characterization of the function, modes of action, and regulation of CTR and other molecular factors that functionally cooperate with CTR for copper transport, compartmentalization, incorporation into cuproproteins, and detoxification has revealed that organisms have evolved fascinating mechanisms for tight control of copper metabolism. This research progress further indicates the significance of copper in health and disease and opens avenues for therapeutic control of copper bioavailability and its metabolic pathways. PMID:23506889

ATP7A is a novel target of retinoic acid receptor β2 in neuroblastoma cells

PubMed Central

Bohlken, A; Cheung, B B; Bell, J L; Koach, J; Smith, S; Sekyere, E; Thomas, W; Norris, M; Haber, M; Lovejoy, D B; Richardson, D R; Marshall, G M

2009-01-01

Increased retinoic acid receptor β (RARβ2) gene expression is a hallmark of cancer cell responsiveness to retinoid anticancer effects. Moreover, low basal or induced RARβ2 expression is a common feature of many human cancers, suggesting that RARβ2 may act as a tumour suppressor gene in the absence of supplemented retinoid. We have previously shown that low RARβ2 expression is a feature of advanced neuroblastoma. Here, we demonstrate that the ABC domain of the RARβ2 protein alone was sufficient for the growth inhibitory effects of RARβ2 on neuroblastoma cells. ATP7A, the copper efflux pump, is a retinoid-responsive gene, was upregulated by ectopic overexpression of RARβ2. The ectopic overexpression of the RARβ2 ABC domain was sufficient to induce ATP7A expression, whereas, RARβ2 siRNA blocked the induction of ATP7A expression in retinoid-treated neuroblastoma cells. Forced downregulation of ATP7A reduced copper efflux and increased viability of retinoid-treated neuroblastoma cells. Copper supplementation enhanced cell growth and reduced retinoid-responsiveness, whereas copper chelation reduced the viability and proliferative capacity. Taken together, our data demonstrates ATP7A expression is regulated by retinoic acid receptor β and it has effects on intracellular copper levels, revealing a link between the anticancer action of retinoids and copper metabolism. PMID:19127267

Effectiveness of the Preservation Protocol within the Environmental Protection Agency (EPA) Method 200.8 for Soluble and Particulate Lead Recovery in Drinking Water

EPA Science Inventory

Lead (Pb) is a toxic trace metal that is regulated in drinking water. The U.S. Environmental Protection Agency (USEPA) issued the Lead and Copper Rule (LCR), which defines the action level for lead at the tap as 0.015 mg/L. Researchers and drinking water utilities typically emplo...

Comparison between micro- and nanosized copper oxide and water soluble copper chloride: interrelationship between intracellular copper concentrations, oxidative stress and DNA damage response in human lung cells.

PubMed

Strauch, Bettina Maria; Niemand, Rebecca Katharina; Winkelbeiner, Nicola Lisa; Hartwig, Andrea

2017-08-01

Nano- and microscale copper oxide particles (CuO NP, CuO MP) are applied for manifold purposes, enhancing exposure and thus the potential risk of adverse health effects. Based on the pronounced in vitro cytotoxicity of CuO NP, systematic investigations on the mode of action are required. Therefore, the impact of CuO NP, CuO MP and CuCl 2 on the DNA damage response on transcriptional level was investigated by quantitative gene expression profiling via high-throughput RT-qPCR. Cytotoxicity, copper uptake and the impact on the oxidative stress response, cell cycle regulation and apoptosis were further analysed on the functional level. Cytotoxicity of CuO NP was more pronounced when compared to CuO MP and CuCl 2 in human bronchial epithelial BEAS-2B cells. Uptake studies revealed an intracellular copper overload in the soluble fractions of both cytoplasm and nucleus, reaching up to millimolar concentrations in case of CuO NP and considerably lower levels in case of CuO MP and CuCl 2 . Moreover, CuCl 2 caused copper accumulation in the nucleus only at cytotoxic concentrations. Gene expression analysis in BEAS-2B and A549 cells revealed a strong induction of uptake-related metallothionein genes, oxidative stress-sensitive and pro-inflammatory genes, anti-oxidative defense-associated genes as well as those coding for the cell cycle inhibitor p21 and the pro-apoptotic Noxa and DR5. While DNA damage inducible genes were activated, genes coding for distinct DNA repair factors were down-regulated. Modulation of gene expression was most pronounced in case of CuO NP as compared to CuO MP and CuCl 2 and more distinct in BEAS-2B cells. GSH depletion and activation of Nrf2 in HeLa S3 cells confirmed oxidative stress induction, mainly restricted to CuO NP. Also, cell cycle arrest and apoptosis induction were most distinct for CuO NP. The high cytotoxicity and marked impact on gene expression by CuO NP can be ascribed to the strong intracellular copper ion release, with subsequent copper accumulation in the cytoplasm and the nucleus. Modulation of gene expression by CuO NP appeared to be primarily oxidative stress-related and was more pronounced in redox-sensitive BEAS-2B cells. Regarding CuCl 2 , relevant modulations of gene expression were restricted to cytotoxic concentrations provoking impaired copper homoeostasis.

One-pot synthesis of 2,5-dihydropyrroles from terminal alkynes, azides, and propargylic alcohols by relay actions of copper, rhodium, and gold.

PubMed

Miura, Tomoya; Tanaka, Takamasa; Matsumoto, Kohei; Murakami, Masahiro

2014-12-01

Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gives 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propargylic alcohols. Initially, copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides affords 1-sulfonyl-1,2,3-triazoles, which then react with propargylic alcohols under the catalysis of rhodium. The resulting alkenyl propargyl ethers subsequently undergo the thermal Claisen rearrangement to give α-allenyl-α-amino ketones. Finally, a gold catalyst prompts 5-endo cyclization to produce 2,5-dihydropyrroles. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Copper intake and blood levels as risk factors for atheromatous disease].

PubMed

Albala, C; Salazar, G; Vío, F; Araya, F; Feuerhacke, W; Olivares, S; Alvarez, G

1997-08-01

Copper is part of antioxidant enzymes and could have a cardiovascular protective effect. A higher cardiovascular risk has been associated with high as well as low plasma copper levels. To search for differences in copper intake and plasma levels between patients with coronary artery or cerebrovascular diseases and normal subjects. Zinc and copper intake, plasma levels and serum lipid levels were measured in 20 patients with cerebrovascular disease, 20 patients with an acute myocardial infarction and 40 subjects hospitalized for elective surgery, that served as controls. Copper and zinc intake was below recommended allowances in all subjects. Serum zinc and copper levels did not differ in the three study groups. In patients with myocardial infarction a weak correlation was found between serum copper and total cholesterol (r = 0.24; p < 0.05) and LDL cholesterol (r = 0.31; p < 0.05). No differences in copper levels were found in subjects with atherosclerosis and controls. The correlation between serum copper and cholesterol deserves further investigation.

[Influence of the earthworm Lumbricus terrestris on soil solution complexation capacity].

PubMed

el Gharmali, A; Rada, A; el Meray, M; Nejmeddine, A

2001-04-01

Four soil samples highly contaminated with metals of urban and mine origin (SE1, SE2, SM1, SM2) and having different physico-chemical proprieties were selected to study copper complexation capacity (LT) of soil solution. The effect of Lumbricus terrestris on copper complexation capacity of soil solution was investigated on SE1 and SE2. The complexation capacity was estimated by amperometric titration of soil solution by copper. Free hydrated cation and labile complexes of copper were determined by DPASV. The results show that the copper complexation capacity variation depends on the physico-chemical characteristics of soils, particularly pH. Thus, the values of copper complexation capacity are 0; 0.6 x 10(-7); 1.8 x 10(-7) and 5.5 x 10(-7) mol l-1 respectively for SM2; SM1; SE1 and SE2 which are pH 5; 5.4; 6.5 and 7.4. Based on these results, the bioavailability levels of heavy metals show the following pool ranking: SM2 > SM1 > SE1 > SE2. The copper complexation capacity of soil solution increases with the soil disturbance by Lumbricus terrestris. This is more obvious when the time of disturbance by lumbrics is longer. Indeed, average values determined for 1 month and 3 months are 3.8 x 10(-7) and 7.8 x 10(-7) mol l-1 for SE1; 7.7 x 10(-7) and 15.2 x 10(-7) mol l-1 for SE2 respectively. It seems that the action of earthworm on soil can contribute to the decrease of bioavailability of heavy metals, particularly copper.

Exposure to arsenic and lead of children living near a copper-smelter in San Luis Potosi, Mexico: Importance of soil contamination for exposure of children.

PubMed

Carrizales, Leticia; Razo, Israel; Téllez-Hernández, Jesús I; Torres-Nerio, Rocío; Torres, Arturo; Batres, Lilia E; Cubillas, Ana-Cristina; Díaz-Barriga, Fernando

2006-05-01

The objective of this study was to assess the levels of soil contamination and child exposure in areas next to a primary smelter (arsenic-copper metallurgical) located in the community of Morales in San Luis Potosi, Mexico. In Morales, 90% of the soil samples studied in this work were above 400 mg/kg of lead, and above 100 mg/kg of arsenic, which are guidelines recommended by the United States Environmental Protection Agency (EPA). Bioaccessibility of these metals was studied in vitro in 10 soil samples; the median values of bioaccessibility obtained in these samples were 46.5% and 32.5% for arsenic and lead. Since the concentrations of arsenic and lead in soil were above normal values, and taking into account the bioaccessibility results, exposure to these metals was evaluated in children. Regarding lead, children aged 3-6 years had the highest mean blood lead levels; furthermore, 90% of them had concentrations above 10 microg/dl (CDC's action level). Total urinary arsenic was higher in children aged 8-9 yr; however, the percentage of children with concentrations above 50 microg/g creatinine (CDC's action level) or 100 microg/g creatinine (World Health Organization [WHO] action level) was similar among different age groups. Using the EPAs integrated exposure uptake biokinetic model for lead in children (IEUBK), we estimated that 87% of the total lead in blood is obtained from the soil/dust pathway. The exposure dose to arsenic, estimated for the children living in Morales using Monte Carlo analysis and the arsenic concentrations found in soil, was above the EPA's reference dose. With all these results, it is evident that studies are needed in order to identify adverse health effects in children living in Morales; nevertheless, it is more important to develop a risk reduction program as soon as possible.

Copper tolerance in clones of Agrostis gigantea from a mine waste site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, G.D.; Courtin, G.M.; Rauser, W.E.

1977-04-15

A mine waste site from Sudbury, Ontario, contaminated with heavy metals is described. The dominant vegetative cover was formed by two grasses: Agrostis gigantea Roth. and Agrostis scabra Willd. Testing of 10 clones of A. gigantea from the roast bed and an adjoining area for copper tolerance showed that two clones collected from the roast bed were tolerant to increased copper levels. Copper tolerance was found in clones growing on soils with high copper contents and low pHs. The combination of high copper content and low pH brought about a high level of extractable copper within the soil. Soils withmore » equally high copper levels but higher pHs and therefore low extractable-copper levels did not support copper-tolerant clones.« less

Serum copper levels in users of multiload intra-uterine contraceptive devices.

PubMed

Arowojolu, A O; Otolorin, E O; Ladipo, O A

1989-12-01

The systemic absorption of copper incorporated into multiload intra-uterine contraceptive devices (IUDs), as indicated by serum copper levels in users of such devices, was assessed in a prospective longitudinal study. One hundred and ten healthy Nigerian women using either multiload copper 250 (MLCU 250) or multiload copper 375 (MLCU 375) IUDs participated in the study. Their serum copper levels were estimated serially during 12 months of continuous use of the devices. The mean (+/- s.e.m.) pre-insertion serum copper levels of our subjects using MLCU 250 (17.0 +/- 3 mumol/l) and MLCU 375 (16.7 +/- 0.5 mumol/l) were found to be lower than those reported in Americans (22.2 mumol/l) and in Germans (20.2 mumol/l), although similar to levels in Indians (17.0 mumol/l). There was no significant difference in the mean serum copper levels estimated before and after 1 month of continuous use of the device. Serial estimations of the serum copper levels in users showed that there was no alteration in these levels after a period of 12 months of continuous IUD use. We therefore conclude that the copper incorporated into multiload IUDs appears not to influence the concentration of serum copper of users.

Bioavailable copper modulates oxidative phosphorylation and growth of tumors

PubMed Central

Ishida, Seiko; Andreux, Pénélope; Poitry-Yamate, Carole; Auwerx, Johan; Hanahan, Douglas

2013-01-01

Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment. PMID:24218578

Roles of Copper-Binding Proteins in Breast Cancer.

PubMed

Blockhuys, Stéphanie; Wittung-Stafshede, Pernilla

2017-04-20

Copper ions are needed in several steps of cancer progression. However, the underlying mechanisms, and involved copper-binding proteins, are mainly elusive. Since most copper ions in the body (in and outside cells) are protein-bound, it is important to investigate what copper-binding proteins participate and, for these, how they are loaded with copper by copper transport proteins. Mechanistic information for how some copper-binding proteins, such as extracellular lysyl oxidase (LOX), play roles in cancer have been elucidated but there is still much to learn from a biophysical molecular viewpoint. Here we provide a summary of copper-binding proteins and discuss ones reported to have roles in cancer. We specifically focus on how copper-binding proteins such as mediator of cell motility 1 (MEMO1), LOX, LOX-like proteins, and secreted protein acidic and rich in cysteine (SPARC) modulate breast cancer from molecular and clinical aspects. Because of the importance of copper for invasion/migration processes, which are key components of cancer metastasis, further insights into the actions of copper-binding proteins may provide new targets to combat cancer.

[Use of copper oxide wire particles (Copinox) for the prevention of congenital copper deficiency in a herd of German Improved Fawn breed of goat].

PubMed

Winter, P; Hochsteiner, W; Chizzola, R

2004-10-01

In a herd of German Improved Fawn breed of goat in the year 2000 neonatal kid losses due to congenital copper deficiencies were observed. To clarify the problems and to prevent losses in the next breeding season serum copper levels of 10 dams and four control Boer goats were investigated at four time points during one year. Additionally ten kids of the following year were sampled and the serum copper levels were studied. Immediatly after parturition and 8 weeks later the dams showed low serum copper levels (10.4 +/- 11.1 micromol/l, 5.7 +/- 2.9 micromol/l resp.). At the end of the pasture season an increase of serum copper could be measured (19.3 +/- 16.0 micromol/l). To prevent enzootic ataxia due to congenital copper deficiency, the dams were treated with copper oxide wire particles in the next late gestation. At this time point serum copper concentrations started to decrease (18.5 +/- 8.4 micromol/l). The re-examination 3 month later demonstrated an increase of the serum mean copper concentrations up to 23.4 micromol/l in the dams and to 16.2 micromol/l in the kids. The serum copper levels were significantly higher compared to the levels the year before. Big variation of the serum copper levels in the control Boer goats occurred during the year, but no clinical symptoms of copper deficiency could be observed. The copper levels in the grass and soil samples were 6.8 mg/kg and 0.2 mg/kg dry substance, respectively. A secondary copper deficiency based on cadmium could be excluded through the low levels of soil samples. The contents of sulphur and molybdenum were not determined. The results indicate that the German Improved Fawn breed of goats suffered from a primary copper deficiency due to the inefficient mineral supplementation. The administration of Copinox in the last third of the gestation leads to a continious raising of the copper concentrations in the serum and is suited to prevent ataxia due to congential copper deficiency in neonatal kids.

Copper deficiency in Tule Elk at Point Reyes, California

USGS Publications Warehouse

Gogan, Peter J.P.; Jessup, David A.; Akeson, Mark

1989-01-01

Tule elk (Cervus elaphus nannodes) reintroduced to Point Reyes, Calif., in 1978 exhibited gross signs of copper deficiency by June 1979. Copper levels in liver (x=5.9 ppm) and serum (0.42 ppm) of elk in Point Reyes were below levels in adult tule elk from other locations in California (liver, x=80 ppm; serum, x=1.4 ppm). These levels were consistent with documented copper deficiencies in wild and domestic ruminants. Copper serum levels increased in response to copper enriched dietary supplements and declined after the elk stopped eating the supplements. Analysis of plant and soil samples showed both are deficient in copper and normal in molybdenum and sulfur-sulfates. Deficiency in plants and soils at Point Reyes are probably due to low copper levels in the underlying granitic parent material.

Final Approval of Arizona Air Plan Revision; Lead-bearing Fugitive Dust Associated With Hayden, AZ Copper Smelter

EPA Pesticide Factsheets

EPA is taking final action to approve a revision to a portion of the Arizona State Implementation Plan (SIP) concerning emissions of lead-bearing fugitive dust associated with the primary copper smelter located in Hayden, Arizona.

Study of Pyrex and quartz insulators contamination effect on the X-ray intensity in a 4-kJ plasma focus device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Habibi, M., E-mail: mortezahabibi@aut.ac.ir; Sharifi, R.; Amrollahi, R.

2013-12-15

The variation of the X-ray intensity has been investigated with the Pyrex and quartz insulators surface contamination in a 4-kJ plasma focus device with argon gas at 11.5-kV charging voltage. Elemental analysis (EDAX) showed that the Cu evaporated from the electrode material and was deposited on the sleeve surface improves the breakdown conditions. A small level of sleeve contamination by copper is found to be essential for good focusing action and high HXR intensity. The SEM imaging showed the grain-type structure of Cu formed on the surface and it changed the surface property. Resistance measurements of original and coated Pyrexmore » surface proved that the copper deposition on the sleeve surface will reduce its resistance as compared to the almost infinitely large resistance of the uncontaminated sleeve. As the contamination is surpassed to some critical level, the HXR intensity from the device is deteriorated.« less

Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

PubMed

Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

2017-07-01

Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P < 0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration. In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

Detection of Genetically Altered Copper Levels in Drosophila Tissues by Synchrotron X-Ray Fluorescence Microscopy

PubMed Central

Lye, Jessica C.; Hwang, Joab E. C.; Paterson, David; de Jonge, Martin D.; Howard, Daryl L.; Burke, Richard

2011-01-01

Tissue-specific manipulation of known copper transport genes in Drosophila tissues results in phenotypes that are presumably due to an alteration in copper levels in the targeted cells. However direct confirmation of this has to date been technically challenging. Measures of cellular copper content such as expression levels of copper-responsive genes or cuproenzyme activity levels, while useful, are indirect. First-generation copper-sensitive fluorophores show promise but currently lack the sensitivity required to detect subtle changes in copper levels. Moreover such techniques do not provide information regarding other relevant biometals such as zinc or iron. Traditional techniques for measuring elemental composition such as inductively coupled plasma mass spectroscopy are not sensitive enough for use with the small tissue amounts available in Drosophila research. Here we present synchrotron x-ray fluorescence microscopy analysis of two different Drosophila tissues, the larval wing imaginal disc, and sectioned adult fly heads and show that this technique can be used to detect changes in tissue copper levels caused by targeted manipulation of known copper homeostasis genes. PMID:22053217

Alternatives to chromated copper arsenate for residential construction

Treesearch

Stan T. Lebow

2004-01-01

For decades chromated copper arsenate (CCA) was the primary preservative for treated wood used in residential construction. However, recent label changes submitted by CCA registrants will withdraw CCA from most residential applications. This action has increased interest in arsenic free preservative systems that have been standardized by the American Wood Preservers...

Copper-redox cycling by coumarin-di(2-picolyl)amine hybrid molecule leads to ROS-mediated DNA damage and apoptosis: A mechanism for cancer chemoprevention.

PubMed

Khan, Saman; Zafar, Atif; Naseem, Imrana

2018-06-25

Coumarin is an important bioactive pharmacophore. It is found in plants as a secondary metabolite and exhibits diverse pharmacological properties including anticancer effects against different malignancies. Therapeutic efficacy of coumarin derivatives depends on the pattern of substitution and conjugation with different moieties. Cancer cells contain elevated copper as compared to normal cells that plays a role in angiogenesis. Thus, targeting copper in malignant cells via copper chelators can serve as an attractive targeted anticancer strategy. Our previous efforts led to the synthesis of di(2-picolyl)amine-3(bromoacetyl)coumarin hybrid molecule (ligand-L) endowed with DNA/Cu(II) binding properties, and ROS generation ability in the presence of copper ions. In the present study, we aimed to validate copper-dependent cytotoxic action of ligand-L against malignant cells. For this, we used a cellular model system of copper (Cu) overloaded lymphocytes (CuOLs) to simulate malignancy-like condition. In CuOLs, lipid peroxidation/protein carbonylation, ROS generation, DNA fragmentation and apoptosis were investigated in the presence of ligand-L. Results showed that ligand-L-Cu(II) interaction leads to ROS generation, lipid peroxidation/protein carbonylation (oxidative stress parameters), DNA damage, up-regulation of p53 and mitochondrial-mediated apoptosis in treated lymphocytes. Further, pre-incubation with neocuproine (membrane permeable copper chelator) and ROS scavengers attenuated the DNA damage and apoptosis. These results suggest that cellular copper acts as molecular target for ligand-L to propagate redox cycling and generation of ROS via Fenton-like reaction leading to DNA damage and apoptosis. Further, we showed that ligand-L targets elevated copper in breast cancer MCF-7 and colon cancer HCT116 cells leading to a pro-oxidant inhibition of proliferation of cancer cells. In conclusion, we propose copper-dependent ROS-mediated mechanism for the cytotoxic action of ligand-L in malignant cells. Thus, targeting elevated copper represents an effective therapeutic strategy for selective cytotoxicity against malignant cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Estimating Dermal Transfer of Copper Particles from the ...

EPA Pesticide Factsheets

Lumber pressure-treated with micronized copper was examined for the release of copper and copper micro/nanoparticles using a surface wipe method to simulate dermal transfer. In 2003, the wood industry began replacing CCA treated lumber products for residential use with copper based formulations. Micronized copper (nano to micron sized particles) has become the preferred treatment formulation. There is a lack of information on the release of copper, the fate of the particles during dermal contact, and the copper exposure level to children from hand-to-mouth transfer. For the current study, three treated lumber products, two micronized copper and one ionic copper, were purchased from commercial retailers. The boards were left to weather outdoors for approximately 1 year. Over the year time period, hand wipe samples were collected periodically to determine copper transfer from the wood surfaces. The two micronized formulations and the ionic formulation released similar levels of total copper. The amount of copper released was high initially, but decreased to a constant level (~1.5 mg m-2) after the first month of outdoor exposure. Copper particles were identified on the sampling cloths during the first two months of the experiment, after which the levels of copper were insufficient to collect interpretable data. After 1 month, the particles exhibited minimal changes in shape and size. At the end of 2-months, significant deterioration of the particles was

The effect of binary mixtures of zinc, copper, cadmium, and nickel on the growth of the freshwater diatom Navicula pelliculosa and comparison with mixture toxicity model predictions.

PubMed

Nagai, Takashi; De Schamphelaere, Karel A C

2016-11-01

The authors investigated the effect of binary mixtures of zinc (Zn), copper (Cu), cadmium (Cd), and nickel (Ni) on the growth of a freshwater diatom, Navicula pelliculosa. A 7 × 7 full factorial experimental design (49 combinations in total) was used to test each binary metal mixture. A 3-d fluorescence microplate toxicity assay was used to test each combination. Mixture effects were predicted by concentration addition and independent action models based on a single-metal concentration-response relationship between the relative growth rate and the calculated free metal ion activity. Although the concentration addition model predicted the observed mixture toxicity significantly better than the independent action model for the Zn-Cu mixture, the independent action model predicted the observed mixture toxicity significantly better than the concentration addition model for the Cd-Zn, Cd-Ni, and Cd-Cu mixtures. For the Zn-Ni and Cu-Ni mixtures, it was unclear which of the 2 models was better. Statistical analysis concerning antagonistic/synergistic interactions showed that the concentration addition model is generally conservative (with the Zn-Ni mixture being the sole exception), indicating that the concentration addition model would be useful as a method for a conservative first-tier screening-level risk analysis of metal mixtures. Environ Toxicol Chem 2016;35:2765-2773. © 2016 SETAC. © 2016 SETAC.

CopZ from Bacillus subtilis interacts in vivo with a copper exporting CPx-type ATPase CopA.

PubMed

Radford, David S; Kihlken, Margaret A; Borrelly, Gilles P M; Harwood, Colin R; Le Brun, Nick E; Cavet, Jennifer S

2003-03-14

The structure of the hypothetical copper-metallochaperone CopZ from Bacillus subtilis and its predicted partner CopA have been studied but their respective contributions to copper export, -import, -sequestration and -supply are unknown. DeltacopA was hypersensitive to copper and contained more copper atoms cell(-1) than wild-type. Expression from the copA operator-promoter increased in elevated copper (not other metals), consistent with a role in copper export. A bacterial two-hybrid assay revealed in vivo interaction between CopZ and the N-terminal domain of CopA but not that of a related transporter, YvgW, involved in cadmium-resistance. Activity of copper-requiring cytochrome caa(3) oxidase was retained in deltacopZ and deltacopA. DeltacopZ was only slightly copper-hypersensitive but deltacopZ/deltacopA was more sensitive than deltacopA, implying some action of CopZ that is independent of CopA. Significantly, deltacopZ contained fewer copper atoms cell(-1) than wild-type under these conditions. CopZ makes a net contribution to copper sequestration and/or recycling exceeding any donation to CopA for export.

The Role of Grain Size on Neutron Irradiation Response of Nanocrystalline Copper

PubMed Central

Mohamed, Walid; Miller, Brandon; Porter, Douglas; Murty, Korukonda

2016-01-01

The role of grain size on the developed microstructure and mechanical properties of neutron irradiated nanocrystalline copper was investigated by comparing the radiation response of material to the conventional micrograined counterpart. Nanocrystalline (nc) and micrograined (MG) copper samples were subjected to a range of neutron exposure levels from 0.0034 to 2 dpa. At all damage levels, the response of MG-copper was governed by radiation hardening manifested by an increase in strength with accompanying ductility loss. Conversely, the response of nc-copper to neutron irradiation exhibited a dependence on the damage level. At low damage levels, grain growth was the primary response, with radiation hardening and embrittlement becoming the dominant responses with increasing damage levels. Annealing experiments revealed that grain growth in nc-copper is composed of both thermally-activated and irradiation-induced components. Tensile tests revealed minimal change in the source hardening component of the yield stress in MG-copper, while the source hardening component was found to decrease with increasing radiation exposure in nc-copper. PMID:28773270

Alternatives to chromated copper arsenate (CCA) for residential construction.

Treesearch

Stan Lebow

2004-01-01

For decades chromated copper arsenate (CCA) was the primary preservative for treated wood used in residential construction. However, recent label changes submitted by CCA registrants will withdraw CCA from most residential applications. This action has increased interest in arsenic-free preservative systems that have been standardized by the American Wood Preservers’...

The Effect of Silver and Copper Nanoparticles on the Wheat— Pseudocercosporella herpotrichoides Pathosystem

NASA Astrophysics Data System (ADS)

Belava, V. N.; Panyuta, O. O.; Yakovleva, G. M.; Pysmenna, Y. M.; Volkogon, M. V.

2017-04-01

The paper covers the study of the effects of silver (Ag) and copper (Cu) nanoparticles on wheat— Pseudocercosporella herpotrichoides pathosystem in general and, separately, on their interaction both with the plant and with the pathogen. Plants, treated with nonionic colloidal solutions of biogenic metal nanoparticles of Ag and Cu, have taken seed treatment as stress and have demonstrated the same changes in the dynamic patterns of thiobarbituric acid reactive substances (TBARS) content as a seedling infection or in its combination with a nanoparticle treatment. The wheat variety, which is sensitive to pathogen action, has showed a substantial (100%) increase in the TBARS contents, while the other varieties has shown lesser (40%) changes in the TBARS content as compared to the control. Besides, both silver and copper nanoparticles have not affected the growth and development of P. herpotrichoides, thus suggesting that the effect of nanoparticles is determined by the plant's responses to the pathogen rather than the phytotoxic action of the copper or silver nanoparticles, at least during the initial stages of the pathological process.

Mechanism of Silver Nanoparticles Action on Insect Pigmentation Reveals Intervention of Copper Homeostasis

PubMed Central

Armstrong, Najealicka; Ramamoorthy, Malaisamy; Lyon, Delina; Jones, Kimberly; Duttaroy, Atanu

2013-01-01

Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities past that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, we attempted to monitor the effects of AgNPs at a nonlethal concentration on wild type Drosophila melanogaster by exposing them throughout their development. All adult flies raised in AgNP doped food showed that up to 50 mg/L concentration AgNP has no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised due to AgNP feeding. Determination of the amount of free ionic silver (Ag+) led us to claim that the observed biological effects have resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, are decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Consequently, we propose a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explains the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, we claim that Drosophila, an established genetic model system, can be well utilized for further understanding of the biological effects of nanoparticles. PMID:23308159

Juxtaposition of chemical and mutation-induced developmental defects in zebrafish reveal a copper-chelating activity for kalihinol F.

PubMed

Sandoval, Imelda T; Manos, Elizabeth J; Van Wagoner, Ryan M; Delacruz, Richard Glenn C; Edes, Kornelia; Winge, Dennis R; Ireland, Chris M; Jones, David A

2013-06-20

A major hurdle in using complex systems for drug screening is the difficulty of defining the mechanistic targets of small molecules. The zebrafish provides an excellent model system for juxtaposing developmental phenotypes with mechanism discovery using organism genetics. We carried out a phenotype-based screen of uncharacterized small molecules in zebrafish that produced a variety of chemically induced phenotypes with potential genetic parallels. Specifically, kalihinol F caused an undulated notochord, defects in pigment formation, hematopoiesis, and neural development. These phenotypes were strikingly similar to the zebrafish mutant, calamity, an established model of copper deficiency. Further studies into the mechanism of action of kalihinol F revealed a copper-chelating activity. Our data support this mechanism of action for kalihinol F and the utility of zebrafish as an effective system for identifying therapeutic and target pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

Control of the Structure of Diffusion Layer in Carbon Steels Under Nitriding with Preliminary Deposition of Copper Oxide Catalytic Films

NASA Astrophysics Data System (ADS)

Petrova, L. G.; Aleksandrov, V. A.; Malakhov, A. Yu.

2017-07-01

The effect of thin films of copper oxide deposited before nitriding on the phase composition and the kinetics of growth of diffusion layers in carbon steels is considered. The process of formation of an oxide film involves chemical reduction of pure copper on the surface of steel specimens from a salt solution and subsequent oxidation under air heating. The oxide film exerts a catalytic action in nitriding of low- and medium-carbon steels, which consists in accelerated growth of the diffusion layer, the nitride zone in the first turn. The kinetics of the nitriding process and the phase composition of the layer are controlled by the thickness of the copper oxide precursor, i.e., the deposited copper film.

Copper toxicity in the crab, Scylla serrata, copper levels in tissues and regulation after exposure to a copper-rich medium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arumugam, M.; Ravindranath, M.H.

1987-10-01

In the decapod crustaceans copper is distributed in various tissues. In these animals the tissue copper generally exists in four forms; ionic, bound to proteins, lipids and membrane. In the estuarine crab Scylla serrata, the haemolymph copper exists only in association with proteins, whereas in the hepatopancreas it exists in all the four forms and in gills it exists in all the forms except in combination with lipids. Although food is the major source of copper in decapod crustaceans evidence indicate that copper may be directly obtained from the environment. It was postulated earlier that in Scylla serrata the haemolymphmore » and hepatopancreas may be involved in copper regulation. In the present work the authors have studied the nature and levels of copper in different tissues after exposing the crabs to copper-rich medium. The results indicate the relative importance of various tissues in accumulation an the possible mechanisms of regulation of the environmental copper. Besides, as a pre-requisite for studies of this kind, the toxic levels for different forms of copper were estimated since the form of toxicant is known to influence the toxicity to the decapod crustaceans.« less

77 FR 36980 - Migratory Bird Hunting; Application for Approval of Copper-Clad Iron Shot as Nontoxic for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... of Copper-Clad Iron Shot as Nontoxic for Waterfowl Hunting AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of application for nontoxic shot approval. SUMMARY: We, the U.S. Fish and Wildlife Service, announce that Environ- Metal, Inc., of Sweet Home, Oregon, has applied for our approval of shot...

The Yeast Copper Response Is Regulated by DNA Damage

PubMed Central

Dong, Kangzhen; Addinall, Stephen G.; Lydall, David

2013-01-01

Copper is an essential but potentially toxic redox-active metal, so the levels and distribution of this metal are carefully regulated to ensure that it binds to the correct proteins. Previous studies of copper-dependent transcription in the yeast Saccharomyces cerevisiae have focused on the response of genes to changes in the exogenous levels of copper. We now report that yeast copper genes are regulated in response to the DNA-damaging agents methyl methanesulfonate (MMS) and hydroxyurea by a mechanism(s) that requires the copper-responsive transcription factors Mac1 and AceI, copper superoxide dismutase (Sod1) activity, and the Rad53 checkpoint kinase. Furthermore, in copper-starved yeast, the response of the Rad53 pathway to MMS is compromised due to a loss of Sod1 activity, consistent with the model that yeast imports copper to ensure Sod1 activity and Rad53 signaling. Crucially, the Mac1 transcription factor undergoes changes in its redox state in response to changing levels of copper or MMS. This study has therefore identified a novel regulatory relationship between cellular redox, copper homeostasis, and the DNA damage response in yeast. PMID:23959798

Copper accumulation in senescent cells: Interplay between copper transporters and impaired autophagy.

PubMed

Masaldan, Shashank; Clatworthy, Sharnel A S; Gamell, Cristina; Smith, Zoe M; Francis, Paul S; Denoyer, Delphine; Meggyesy, Peter M; Fontaine, Sharon La; Cater, Michael A

2018-06-01

Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g. diabetes). We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial cells and human diploid fibroblasts] in vitro. Elevated copper in senescent MEFs was accompanied by elevated levels of high-affinity copper uptake protein 1 (Ctr1), diminished levels of copper-transporting ATPase 1 (Atp7a) (copper export) and enhanced antioxidant defence reflected by elevated levels of glutathione (GSH), superoxide dismutase 1 (SOD1) and glutaredoxin 1 (Grx1). The levels of intracellular copper were further increased in senescent MEFs cultured in copper supplemented medium and in senescent Mottled Brindled (Mo br ) MEFs lacking functional Atp7a. Finally, we demonstrated that the restoration/preservation of autophagic-lysosomal degradation in senescent MEFs following rapamycin treatment correlated with attenuation of copper accumulation in these cells despite a further decrease in Atp7a levels. This study for the first time establishes a link between Atp7a and the autophagic-lysosomal pathway, and a requirement for both to effect efficient copper export. Such a connection between cellular autophagy and copper homeostasis is significant, as both have emerged as important facets of age-associated degenerative disease. Copyright © 2018. Published by Elsevier B.V.

High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats

PubMed Central

Ha, Jung-Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen R.; Collins, James F.

2016-01-01

Iron-copper interactions were described decades ago; however, molecular mechanisms linking the two essential minerals remain largely undefined. Investigations in humans and other mammals noted that copper levels increase in the intestinal mucosa, liver and blood during iron deficiency, tissues all important for iron homeostasis. The current study was undertaken to test the hypothesis that dietary copper influences iron homeostasis during iron deficiency and iron overload. We thus fed weanling, male Sprague-Dawley rats (n = 6-11/group) AIN-93G-based diets containing high (~8800 ppm), adequate (~80) or low (~11) iron in combination with high (~183), adequate (~8) or low (~0.9) copper for 5 weeks. Subsequently, the iron- and copper-related phenotype of the rats was assessed. Rats fed the low-iron diets grew slower than controls, with changes in dietary copper not further influencing growth. Unexpectedly, however, high-iron (HFe) feeding also impaired growth. Furthermore, consumption of the HFe diet caused cardiac hypertrophy, anemia, low serum and tissue copper levels and decreased circulating ceruloplasmin activity. Intriguingly, these physiologic perturbations were prevented by adding extra copper to the HFe diet. Furthermore, higher copper levels in the HFe diet increased serum nonheme iron concentration and transferrin saturation, exacerbated hepatic nonheme iron loading and attenuated splenic nonheme iron accumulation. Moreover, serum erythropoietin levels, and splenic erythroferrone and hepatic hepcidin mRNA levels were altered by the dietary treatments in unanticipated ways, providing insight into how iron and copper influence expression of these hormones. We conclude that high-iron feeding of weanling rats causes systemic copper deficiency, and further, that copper influences the iron-overload phenotype. PMID:27537180

A cytosolic copper storage protein provides a second level of copper tolerance in Streptomyces lividans.

PubMed

Straw, Megan L; Chaplin, Amanda K; Hough, Michael A; Paps, Jordi; Bavro, Vassiliy N; Wilson, Michael T; Vijgenboom, Erik; Worrall, Jonathan A R

2018-01-24

Streptomyces lividans has a distinct dependence on the bioavailability of copper for its morphological development. A cytosolic copper resistance system is operative in S. lividans that serves to preclude deleterious copper levels. This system comprises of several CopZ-like copper chaperones and P 1 -type ATPases, predominantly under the transcriptional control of a metalloregulator from the copper sensitive operon repressor (CsoR) family. In the present study, we discover a new layer of cytosolic copper resistance in S. lividans that involves a protein belonging to the newly discovered family of copper storage proteins, which we have named Ccsp (cytosolic copper storage protein). From an evolutionary perspective, we find Ccsp homologues to be widespread in Bacteria and extend through into Archaea and Eukaryota. Under copper stress Ccsp is upregulated and consists of a homotetramer assembly capable of binding up to 80 cuprous ions (20 per protomer). X-ray crystallography reveals 18 cysteines, 3 histidines and 1 aspartate are involved in cuprous ion coordination. Loading of cuprous ions to Ccsp is a cooperative process with a Hill coefficient of 1.9 and a CopZ-like copper chaperone can transfer copper to Ccsp. A Δccsp mutant strain indicates that Ccsp is not required under initial copper stress in S. lividans, but as the CsoR/CopZ/ATPase efflux system becomes saturated, Ccsp facilitates a second level of copper tolerance.

Nano Copper Induces Apoptosis in PK-15 Cells via a Mitochondria-Mediated Pathway.

PubMed

Zhang, Hui; Chang, Zhenyu; Mehmood, Khalid; Abbas, Rao Zahid; Nabi, Fazul; Rehman, Mujeeb Ur; Wu, Xiaoxing; Tian, Xinxin; Yuan, Xiaodan; Li, Zhaoyang; Zhou, Donghai

2018-01-01

Nano-sized copper particles are widely used in various chemical, physical, and biological fields. However, earlier studies have shown that nano copper particles (40-100 μg/mL) can induce cell toxicity and apoptosis. Therefore, this study was conducted to investigate the role of nano copper in mitochondrion-mediated apoptosis in PK-15 cells. The cells were treated with different doses of nano copper (20, 40, 60, and 80 μg/mL) to determine the effects of apoptosis using acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the PK-15 cells were examined using commercially available kits. Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were assessed by real-time PCR. The results revealed that nano copper exposure induced apoptosis and changed the mitochondrial membrane potential. In addition, nano copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS genes at a concentration of 40 μg/mL. To summarize, nano copper significantly (P < 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells. Altogether, these results suggest that nano copper can play an important role in inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by which nano copper induces nephrotoxicity.

The Impact of Hexametaphosphate, Orthophosphate, and Temperature on Copper Corrosion and Release

EPA Science Inventory

Excessive corrosion of copper plumbing can lead to elevated copper levels at consumer’s tap or pinhole leaks. Corrosion control solutions include pH adjustment or phosphate addition. Orthophosphate has been shown to reduce copper levels in some cases while the role of polyphosp...

Zinc and copper status of women by physical activity and menstrual status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, A.; Deuster, P.A.; Kyle, S.B.

The zinc and copper status of 33 eumenorrheic (EU) and 12 amenorrheic (AM) female marathon runners and 19 EU and 8 AM nonrunners were determined from 3-day diet records and plasma and erythrocyte (RBC) levels. The study was conducted as a completely randomized 2 x 2 factorial. Mean daily zinc intakes of all groups fell below the recommended dietary allowances. Copper intakes of runners (EU = 1.3 mg; AM = 1.3 mg) were not significantly different. Menstrual status did not affect plasma zinc, RBC zinc or plasma copper levels. Physical activity however, affected RBC zinc and plasma copper levels. Bothmore » these parameters were significantly higher in runners. These findings suggest that exercise influences blood zinc and copper levels.« less

Acclimation to low level exposure of copper in Bufo arenarum embryos: linkage of effects to tissue residues.

PubMed

Herkovits, Jorge; Pérez-Coll, Cristina Silvia

2007-06-01

The acclimation possibilities to copper in Bufo arenarum embryos was evaluated by means of three different low level copper exposure conditions during 14 days. By the end of the acclimation period the copper content in control embryos was 1.04 +/- 0.09 microg g(-1) (wet weight) while in all the acclimated embryos a reduction of about 25% of copper was found. Thus copper content could be considered as a biomarker of low level exposure conditions. Batches of 10 embryos (by triplicate) from each acclimation condition were challenged with three different toxic concentrations of copper. As a general pattern, the acclimation protocol to copper exerted a transient beneficial effect on the survival of the Bufo arenarum embryos. The acclimation phenomenon could be related to the selection of pollution tolerant organisms within an adaptive process and therefore the persistence of information within an ecological system following a toxicological stressor.

Soy isoflavone supplementation elevates erythrocyte superoxide dismutase, but not plasma ceruloplasmin in postmenopausal breast cancer survivors.

PubMed

DiSilvestro, Robert A; Goodman, Jaime; Dy, Emily; Lavalle, Gregory

2005-02-01

Soy isoflavone antioxidant effects may help prevent breast cancer re-occurrence, but isoflavone estrogen-like actions may increase breast cancer risk. These isoflavone actions can be reflected by effects on two copper enzymes activities, superoxide dismutase 1 (SOD 1), which has antioxidant function relevant to breast cancer prevention, and ceruloplasmin, which has its synthesis up-regulated by estrogen, and for which high values are associated with high breast cancer risk. A soy isoflavone-rich concentrate supplement was examined for effects on these two copper enzyme activities in post-menopausal breast cancer survivors (n = 7) in a crossover design with a placebo (24 days on supplement or placebo; 14 day wash out). The soy concentrate, but not the placebo, increased erythrocyte SOD 1 activities, but not ceruloplasmin activities or protein. The effect on superoxide dismutase activities was not likely due to increased copper intake since analysis of the soy extract showed little copper. The effect on superoxide dismutase was not accompanied by a change in urinary contents of 8-deoxyhydroxyguanosine, a DNA oxidant product, though perhaps this would change with a longer intervention. In summary, in regard to two copper enzyme activities, an isoflavone-rich soy concentrate showed an antioxidant effect considered relevant to breast cancer, but not an effect associated with estrogenic activity and increased breast cancer risk.

Draft Genome Sequences of Four Alteromonas macleodii Strains Isolated from Copper Coupons and Grown Long-Term at Elevated Copper Levels.

PubMed

Cusick, Kathleen D; Dale, Jason R; Little, Brenda J; Biffinger, Justin C

2016-11-23

Alteromonas macleodii is a marine bacterium involved in the early stages of biofouling on ship hulls treated with copper as an antifouling agent. We report here the draft genome sequences of an A. macleodii strain isolated from copper coupons and three laboratory mutants grown long-term at elevated copper levels. Copyright © 2016 Cusick et al.

Chronic copper poisoning in Angora kids.

PubMed

Belford, C J; Raven, C R; Black, H

1989-12-01

The investigation of five field cases of chronic copper poisoning in a group of 100 Angora kids is reported. Toxicity was confirmed by the demonstration of Heinz body anaemias, necrotizing liver disease, haemoglobinuric nephrosis and excessive levels of copper in blood, livers and kidneys. The dietary history of the kids is described. Tissue levels of copper and reported interactions between selenium, zinc and copper are discussed. Therapeutic and preventative measures are suggested.

A practical comparison of Copper Bromide Laser for the treatment of vascular lesions.

PubMed

Lee, SunWoo; Lee, TaeBum; Kim, HoYoun; Kim, JungSoo; Eun, HyeJun; Kim, RyunKyung

2013-01-01

The recent rapid growth in demand for aesthetic non-invasive laser treatments such as unwanted skin rejuvenation, removal of age-related vascular blemishes has led to a boom in the medical devices to treat these conditions. Among diverse laser for skin treatment, copper bromide laser is a very effective, safe, and well tolerated treatment for facial telangiectasia at various energy levels and the most important thing of the copper bromide laser device is that the stability of the energy. However there is no evidence about effective copper bromide laser's energy level for the treatment of vascular lesions. We compared energy stability and treatment performance between two energy levels in 2 W and 8 W which commonly use in laser treatment for the vascular lesions. 8 W copper bromide laser was more stable compared than 2 W copper bromide laser. Also, 8 W copper bromide laser was effectively superior to 2 W copper bromide laser in treatment of vascular legion. Consequently, 8 W copper bromide laser treatment for vascular lesion might be more suitable than 2 W copper bromide laser.

Putting copper into action: copper-impregnated products with potent biocidal activities.

PubMed

Borkow, Gadi; Gabbay, Jeffrey

2004-11-01

Copper ions, either alone or in copper complexes, have been used for centuries to disinfect liquids, solids, and human tissue. Today copper is used as a water purifier, algaecide, fungicide, nematocide, molluscicide, and antibacterial and antifouling agent. Copper also displays potent antiviral activity. We hypothesized that introducing copper into clothing, bedding, and other articles would provide them with biocidal properties. A durable platform technology has been developed that introduces copper into cotton fibers, latex, and other polymeric materials. This study demonstrates the broad-spectrum antimicrobial (antibacterial, antiviral, antifungal) and antimite activities of copper-impregnated fibers and polyester products. This technology enabled the production of antiviral gloves and filters (which deactivate HIV-1 and other viruses), antibacterial self-sterilizing fabrics (which kill antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci), antifungal socks (which alleviate symptoms of athlete's foot), and anti-dust mite mattress covers (which reduce mite-related allergies). These products did not have skin-sensitizing properties, as determined by guine pig maximization and rabbit skin irritation tests. Our study demonstrates the potential use of copper in new applications. These applications address medical issues of the greatest importance, such as viral transmissions; nosocomial, or healthcare-associated, infections; and the spread of antibiotic-resistant bacteria.

The Effect of Some Key Changes in the Chemistry of Water in Relation to Copper and Brass Corrosion Control

NASA Astrophysics Data System (ADS)

Gorovei, M. C.; Benea, L.

2018-06-01

Corrosion means the degradation of the metals or their alloys, under the action of chemical or electrochemical agents from the environment. The complex corrosion phenomenon has a destructive action, generating undesirable economic consequences: metals and labor losses, appreciable reduction in the lifetime of various metal constructions, insecurity in the operation of industrial machinery. Under the current conditions of accelerated growth in the production of material goods, one of the most important issues is the economy of raw materials and materials, energy and labor force. Copper, having a purity of over 99%, is used in the manufacture of gas and water pipes, roofing materials, utensils and ornamental objects. Brass is used in the manufacture of flexible tubes, pipes, coils, cartridges, various electrochemical parts, jewelry, etc. The aim of this research work was to evaluate the corrosion resistance of copper and brass in various solutions: with different chloride ions as 35 g/L NaCl, waste water and tap water. The corrosion behavior of copper and brass was analyzed by electrochemical methods, such as: open circuit potential (OCP), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Pure copper exhibits more noble potential values than its alloy (brass), according to the evolution of free potential in all tested solutions. After performing the electrochemical assays, ex-situ investigations, by optical microscopy, were made and the results confirm that the chloride ions affect the corrosion behavior of copper and brass. Corrosion of materials is a very important process to consider when choosing a material that has to operate in a specific environment.

Membrane Lipid Peroxidation in Copper Alloy-Mediated Contact Killing of Escherichia coli

PubMed Central

Hong, Robert; Kang, Tae Y.; Michels, Corinne A.

2012-01-01

Copper alloy surfaces are passive antimicrobial sanitizing agents that kill bacteria, fungi, and some viruses. Studies of the mechanism of contact killing in Escherichia coli implicate the membrane as the target, yet the specific component and underlying biochemistry remain unknown. This study explores the hypothesis that nonenzymatic peroxidation of membrane phospholipids is responsible for copper alloy-mediated surface killing. Lipid peroxidation was monitored with the thiobarbituric acid-reactive substances (TBARS) assay. Survival, TBARS levels, and DNA degradation were followed in cells exposed to copper alloy surfaces containing 60 to 99.90% copper or in medium containing CuSO4. In all cases, TBARS levels increased with copper exposure levels. Cells exposed to the highest copper content alloys, C11000 and C24000, exhibited novel characteristics. TBARS increased immediately at a very rapid rate but peaked at about 30 min. This peak was associated with the period of most rapid killing, loss in membrane integrity, and DNA degradation. DNA degradation is not the primary cause of copper-mediated surface killing. Cells exposed to the 60% copper alloy for 60 min had fully intact genomic DNA but no viable cells. In a fabR mutant strain with increased levels of unsaturated fatty acids, sensitivity to copper alloy surface-mediated killing increased, TBARS levels peaked earlier, and genomic DNA degradation occurred sooner than in the isogenic parental strain. Taken together, these results suggest that copper alloy surface-mediated killing of E. coli is triggered by nonenzymatic oxidative damage of membrane phospholipids that ultimately results in the loss of membrane integrity and cell death. PMID:22247141

Als1 and Als3 regulate the intracellular uptake of copper ions when Candida albicans biofilms are exposed to metallic copper surfaces.

PubMed

Zheng, Sha; Chang, Wenqiang; Li, Chen; Lou, Hongxiang

2016-05-01

Copper surfaces possess efficient antimicrobial effect. Here, we reported that copper surfaces could inactivate Candida albicans biofilms within 40 min. The intracellular reactive oxygen species in C. albicans biofilms were immediately stimulated during the contact of copper surfaces, which might be an important factor for killing the mature biofilms. Copper release assay demonstrated that the copper ions automatically released from the surface of 1 mm thick copper coupons with over 99.9% purity are not the key determinant for the copper-mediated killing action. The susceptibility test to copper surfaces by using C. albicans mutant strains, which were involved in efflux pumps, adhesins, biofilms formation or osmotic stress response showed that als1/als1 and als3/als3 displayed higher resistance to the copper surface contact than other mutants did. The intracellular concentration of copper ions was lower in als1/als1 and als3/als3 than that in wild-type strain. Transcriptional analysis revealed that the expression of copper transporter-related gene, CRP1, was significantly increased in als1/als1, als3/als3, suggesting a potential role of ALS1 and ALS3 in absorbing ions by regulating the expression of CRP1 This study provides a potential application in treating pathogenic fungi by using copper surfaces and uncovers the roles of ALS1 and ALS3 in absorbing copper ions for C. albicans. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Characteristics and antimicrobial activity of copper-based materials

NASA Astrophysics Data System (ADS)

Li, Bowen

In this study, copper vermiculite was synthesized, and the characteristics, antimicrobial effects, and chemical stability of copper vermiculite were investigated. Two types of copper vermiculite materials, micron-sized copper vermiculite (MCV) and exfoliated copper vermiculite (MECV), are selected for this research. Since most of the functional fillers used in industry products, such as plastics, paints, rubbers, papers, and textiles prefer micron-scaled particles, micron-sized copper vermiculite was prepared by jet-milling vermiculite. Meanwhile, since the exfoliated vermiculite has very unique properties, such as high porosity, specific surface area, high aspect ratio of laminates, and low density, and has been extensively utilized as a functional additives, exfoliated copper vermiculite also was synthesized and investigated. The antibacterial efficiency of copper vermiculite was qualitatively evaluated by the diffusion methods (both liquid diffusion and solid diffusion) against the most common pathogenic species: Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Klebsiella pneumoniae (K. pneumoniae). The result showed that the release velocity of copper from copper vermiculite is very slow. However, copper vermiculite clearly has excellent antibacterial efficiency to S. aureus, K. pneumoniae and E. coli. The strongest antibacterial ability of copper vermiculite is its action on S. aureus. The antibacterial efficiency of copper vermiculite was also quantitatively evaluated by determining the reduction rate (death rate) of E. coli versus various levels of copper vermiculite. 10 ppm of copper vermiculite in solution is sufficient to reduce the cell population of E. coli, while the untreated vermiculite had no antibacterial activity. The slow release of copper revealed that the antimicrobial effect of copper vermiculite was due to the strong interactions between copper ions and bacteria cells. Exfoliated copper vermiculite has even stronger antibacterial activity than copper vermiculite against E. coli. With 200 ppm exfoliated copper vermiculite in bacteria suspension (4.68 ppm of metal copper), the reduction of viable bacteria are 99.8% at 1 hour, and >99.9% at 2 hours. With 10 ppm exfoliated copper vermiculite in bacteria dilution (0.234 ppm of copper atoms), the reduction of viable E. coli reached 98.7% at 1 hour, and >95.6% at 2 hours. Molds have the potential to cause health problems, such as allergic reactions, irritations, and mycotoxins, and damage to buildings, historic relics, properties, etc. Since copper has better antifungal property, an initial antifungal activity of copper vermiculite was evaluated in this study. Fat-free milk was used to develop molds in the test samples by saturated samples. Incubated at 36°C for 48 hours, all of the surfaces of untreated control samples, including micron-sized vermiculite, exfoliated vermiculite, bentonite, and kaolin, have been covered by thick mold layers. However, there were no mold showed on copper vermiculite and exfoliated copper vermiculite. Even after the incubation was lasted for 10 days, copper vermiculite and exfoliated copper vermiculite did not show any mold on the surface. These results exhibited copper vermiculite has excellent antifungal activities against mold. Stability of copper ions in copper vermiculite was measured by aqueous leaching process. Copper vermiculite and exfoliated copper vermiculite were put into distilled water in a ratio of 2.0g/100ml, and then implemented leaching processes by continuously shaking (leaching) and statically storing (soaking) for desired periods of time, respectively. According to the analytic result by inductively coupled plasma spectroscopy (ICP), the major metals released were copper, magnesium, iron, silicon, and aluminum. The release rate of copper depends on the environmental conditions. Under the dynamic leaching condition, all the major elements had shown linear leaching rates, and slowly increases along with the leaching time. Copper concentration in 1 hour leached solutions had sufficient concentration to inhibit E. coli in aqueous solution. Lasting for 1 month, 1 gram of copper vermiculite only released 185mug of copper. At this velocity, 11.5 years are required to completely exhaust the copper atoms from copper vermiculite. A soaking process provided a lower release rate than leaching process. Comparably, exfoliated copper vermiculite had lower copper concentration, stronger antimicrobial effect, but faster release rate than copper vermiculite, due to their different structure characteristics. (Abstract shortened by UMI.)

Copper supplementation amplifies the anti-tumor effect of curcumin in oral cancer cells.

PubMed

Lee, Hui-Mei; Patel, Vyomesh; Shyur, Lie-Fen; Lee, Wai-Leng

2016-11-15

Oral cancer is the sixth most common cancer worldwide and 90% of oral malignancies are caused by oral squamous cell carcinoma (OSCC). Curcumin, a phytocompound derived from turmeric (Curcuma longa) was observed to have anti-cancer activity which can be developed as an alternative treatment option for OSCC. However, OSCC cells with various clinical-pathological features respond differentially to curcumin treatment. Intracellular copper levels have been reported to correlate with tumor pathogenesis and affect the sensitivity of cancer cells to cytotoxic chemotherapy. We hypothesized that intracellular copper levels may affect the sensitivity of oral cancer cells to curcumin. We analysed the correlation between intracellular copper levels and response to curcumin treatment in a panel of OSCC cell lines derived from oral cancer patients. Exogenous copper was supplemented in curcumin insensitive cell lines to observe the effect of copper on curcumin-mediated inhibition of cell viability and migration, as well as induction of oxidative stress and apoptosis. Protein markers of cell migration and oxidative stress were also analysed using Western blotting. Concentrations of curcumin which inhibited 50% OSCC cell viability (IC 50 ) was reduced up to 5 times in the presence of 250 µM copper. Increased copper level in curcumin-treated OSCC cells was accompanied by the induction of intracellular ROS and increased level of Nrf2 which regulates oxidative stress responses in cells. Supplemental copper also inhibited migration of curcumin-treated cells with enhanced level of E-cadherin and decreased vimentin, indications of suppressed epithelial-mesenchymal transition. Early apoptosis was observed in combined treatment but not in treatment with curcumin or copper alone. Supplement of copper significantly enhanced the inhibitory effect of curcumin treatment on migration and viability of oral cancer cells. Together, these findings provide molecular insight into the role of copper in overcoming insensitivity of oral cancer cells to curcumin treatment, suggesting a new strategy for cancer therapy. Copyright © 2016 Elsevier GmbH. All rights reserved.

SOLVING COPPER CORROSION PROBLEMS WHILE MAINTAINING LEAD CONTROL IN A HIGH ALKALINITY WATER USING ORTHOPHOSPHATE

EPA Science Inventory

Lead and Copper Rule sampling in 1992 uncovered high copper levels in many homes in the Indian Hill Water Works, Ohio (IHWW) water system. The 90th percentile copper and lead levels were 1.63 mg/L and 0.012 mg/L, respectively. IHWW supplies water to several suburban communities t...

An Organizational Effectiveness Officer Tackles a Management Job: A follow-Up OE Case Study

DTIC Science & Technology

1981-06-01

time, the COPPER "users manual " had not been updated to reflect the current methods and procedures of the PPSD. RAJ Johnson felt that documentation of...Users’ Manual , now known as PPSD Users’ Manual , to document every action and show document ilow with a flow chart. Also prior to implementing the change...comments is a document to work from. I’ll use it from my level, but let’s push it down in the organizacion ." When interviewed in December, RAJ Johnson was

Formation of copper precipitates in silicon

NASA Astrophysics Data System (ADS)

Flink, Christoph; Feick, Henning; McHugo, Scott A.; Mohammed, Amna; Seifert, Winfried; Hieslmair, Henry; Heiser, Thomas; Istratov, Andrei A.; Weber, Eicke R.

1999-12-01

The formation of copper precipitates in silicon was studied after high-temperature intentional contamination of p- and n-type FZ and Cz-grown silicon and quench to room temperature. With the Transient Ion Drift (TID) technique on p-type silicon a critical Fermi level position at EC-0.2 eV was found. Only if the Fermi level position, which is determined by the concentrations of the acceptors and the copper donors, surpasses this critical value precipitation takes place. If the Fermi level is below this level the supersaturated interstitial copper diffuses out. An electrostatic precipitation model is introduced that correlates the observed precipitation behavior with the electrical activity of the copper precipitates as detected with Deep Level Transient Spectroscopy (DLTS) on n-type and with Minority Carrier Transient Spectroscopy (MCTS) on p-type silicon.

Cancer risk in relation to serum copper levels.

PubMed

Coates, R J; Weiss, N S; Daling, J R; Rettmer, R L; Warnick, G R

1989-08-01

A nested, matched case-control study was conducted to assess the relationship between serum levels of copper and the subsequent risk of cancer. One hundred thirty-three cases of cancer were identified during 1974-1984 among 5000 members of a northwest Washington State employee cohort from whom serum specimens had been previously obtained and stored. Two hundred forty-one controls were selected at random from the cohort and were matched to the cases on the basis of age, sex, race, and date of blood draw. Serum copper levels were measured by atomic absorption spectrometry. Risk of a subsequent diagnosis of cancer was positively associated with serum copper levels, but only among those cases diagnosed within 4 years of the time the serum specimens were collected. Among cases diagnosed more than 4 years after specimen collection, there was no consistent association between serum copper levels and risk. Adjustment for age, sex, race, occupational status, cigarette smoking, family history of cancer, alcohol consumption, and, among females, use of exogenous hormones had no appreciable effect on these relationships. The findings suggest that the presence of cancer may increase serum copper levels several years prior to its diagnosis. They are less supportive of the hypothesis that serum copper levels affect cancer risk.

Multimodal LA-ICP-MS and nanoSIMS imaging enables copper mapping within photoreceptor megamitochondria in a zebrafish model of Menkes disease.

PubMed

Ackerman, Cheri M; Weber, Peter K; Xiao, Tong; Thai, Bao; Kuo, Tiffani J; Zhang, Emily; Pett-Ridge, Jennifer; Chang, Christopher J

2018-03-01

Copper is essential for eukaryotic life, and animals must acquire this nutrient through the diet and distribute it to cells and organelles for proper function of biological targets. Indeed, mutations in the central copper exporter ATP7A contribute to a spectrum of diseases, including Menkes disease, with symptoms ranging from neurodegeneration to lax connective tissue. As such, a better understanding of the fundamental impacts of ATP7A mutations on in vivo copper distributions is of relevance to those affected by these diseases. Here we combine metal imaging and optical imaging techniques at a variety of spatial resolutions to identify tissues and structures with altered copper levels in the Calamity gw71 zebrafish model of Menkes disease. Rapid profiling of tissue slices with LA-ICP-MS identified reduced copper levels in the brain, neuroretina, and liver of Menkes fish compared to control specimens. High resolution nanoSIMS imaging of the neuroretina, combined with electron and confocal microscopies, identified the megamitochondria of photoreceptors as loci of copper accumulation in wildtype fish, with lower levels of megamitochondrial copper observed in Calamity gw71 zebrafish. Interestingly, this localized copper decrease does not result in impaired photoreceptor development or altered megamitochondrial morphology, suggesting the prioritization of copper at sufficient levels for maintaining essential mitochondrial functions. Together, these data establish the Calamity gw71 zebrafish as an optically transparent in vivo model for the study of neural copper misregulation, illuminate a role for the ATP7A copper exporter in trafficking copper to the neuroretina, and highlight the utility of combining multiple imaging techniques for studying metals in whole organism settings with spatial resolution.

Effect of dietary copper addition on lipid metabolism in rabbits

PubMed Central

Lei, Liu; Xiaoyi, Sui; Fuchang, Li

2017-01-01

ABSTRACT The present study was conducted to investigate the effect of copper supplementation on lipid metabolism in rabbits. Our study showed dietary copper addition (5-45 mg/kg) increased body mass gain, but decreased fat and liver weights compared with those in the control group (P < 0.05). Copper (45 mg/kg) addition significantly increased the skeletal muscle weight, but inhibited cytoplasmic lipid accumulation in liver, skeletal muscle and adipose tissue (P < 0.05). Compared with the control group, dietary copper addition (45 mg/kg) significantly increased plasma triglyceride levels but decreased very low density lipoprotein levels (P < 0.05). Copper treatment significantly increased gene expression of carnitine palmitoyltransferase (CPT) 1, CPT2 and peroxisome proliferator-activated receptor (PPAR) a in liver (P < 0.05). In skeletal muscle, CPT1, CPT2, fatty acid transport protein, fatty acid-binding protein, and PPARa mRNA as well as phosphorylated AMP-activated protein kinase (AMPK) levels were significantly up-regulated by copper treatment (P < 0.05). Rabbits receiving copper supplementation had higher CPT1, CPT2, PPARa and hormone-sensitive lipase mRNA levels in adipose tissue (P < 0.05). In conclusion, copper promoted skeletal muscle growth and reduced fat accretion. PPARa signaling in liver, skeletal muscle and adipose tissues and AMPK signaling in skeletal muscle tissue were involved in the regulation of lipid metabolism by copper. PMID:28747869

Listing of color additives for coloring sutures; [phthalocyaninato(2-)] copper. Food and Drug Administration, HHS. Final rule.

PubMed

1999-04-30

The Food and Drug Administration (FDA) is amending the color additive regulations to provide for the safe use of [phthalocyaninato(2-)] copper in coloring nonabsorbable sutures for general and ophthalmic surgery made from a blend of poly(vinylidene fluoride) and poly(vinylidene fluoride-co-hexafluoropropylene). This action responds to a petition filed by Ethicon, Inc.

Ecophysiological and metabolic responses to interactive exposure to nutrients and copper excess in the brown macroalga Cystoseira tamariscifolia.

PubMed

Celis-Plá, Paula S M; Brown, Murray T; Santillán-Sarmiento, Alex; Korbee, Nathalie; Sáez, Claudio A; Figueroa, Félix L

2018-03-01

Global scenarios evidence that contamination due to anthropogenic activities occur at different spatial-temporal scales, being important stressors: eutrophication, due to increased nutrient inputs; and metal pollution, mostly derived from industrial activities. In this study, we investigated ecophysiological and metabolic responses to copper and nutrient excess in the brown macroalga Cystoseira tamariscifolia. Whole plants were incubated in an indoor system under control conditions, two levels of nominal copper (0.5 and 2.0μM), and two levels of nutrient supply for two weeks. Maximal quantum yield (F v /F m ) and maximal electron transport rate (ETR max ) increased under copper exposure. Photosynthetic pigments and phenolic compounds (PC) increased under the highest copper levels. The intra-cellular copper content increased under high copper exposure in both nutrient conditions. C. tamariscifolia from the Atlantic displayed efficient metal exclusion mechanisms, since most of the total copper accumulated by the cell was bound to the cell wall. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acclimation to Low Level Exposure of Copper in Bufo arenarum Embryos: Linkage of Effects to Tissue Residues

PubMed Central

Herkovits, Jorge; Pérez-Coll, Cristina Silvia

2007-01-01

The acclimation possibilities to copper in Bufo arenarum embryos was evaluated by means of three different low level copper exposure conditions during 14 days. By the end of the acclimation period the copper content in control embryos was 1.04 ± 0.09 μg.g−1 (wet weight) while in all the acclimated embryos a reduction of about 25% of copper was found. Thus copper content could be considered as a biomarker of low level exposure conditions. Batches of 10 embryos (by triplicate) from each acclimation condition were challenged with three different toxic concentrations of copper. As a general pattern, the acclimation protocol to copper exerted a transient beneficial effect on the survival of the Bufo arenarum embryos. The acclimation phenomenon could be related to the selection of pollution tolerant organisms within an adaptive process and therefore the persistence of information within an ecological system following a toxicological stressor. PMID:17617681

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution.

PubMed

Denoyer, Delphine; Pearson, Helen B; Clatworthy, Sharnel A S; Smith, Zoe M; Francis, Paul S; Llanos, Roxana M; Volitakis, Irene; Phillips, Wayne A; Meggyesy, Peter M; Masaldan, Shashank; Cater, Michael A

2016-06-14

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed.

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution

PubMed Central

Denoyer, Delphine; Pearson, Helen B.; Clatworthy, Sharnel A.S.; Smith, Zoe M.; Francis, Paul S.; Llanos, Roxana M.; Volitakis, Irene; Phillips, Wayne A.; Meggyesy, Peter M.; Masaldan, Shashank; Cater, Michael A.

2016-01-01

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed. PMID:27175597

The effect of red cell and plasma transfusion on serum zinc and copper levels in the neonate.

PubMed

Lockitch, G; Godolphin, W J; Pendray, M R; Quigley, G

1983-11-01

Transfusion of packed red cells (15 to 20 ml/kg) in 11 preterm infants resulted in a slight increase in mean serum zinc levels on the 3rd post transfusion day but no effect was noted on serum copper levels. No significant difference was found between the changes in serum zinc in 141 paired specimens collected a week apart when zero, one, two or three packed cell transfusions were given in the intervening week. A slight decrease in the mean copper level was noted when one transfusion was given. Transfusion of fresh frozen plasma in six newborns with abdominal wall defects resulted in initial serum copper levels two to three times greater than the reference mean for newborns. No effect was noted on zinc levels. Serum copper results should be interpreted with caution in infants who have been transfused with plasma.

Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.

PubMed

Hu Frisk, Jun Mei; Kjellén, Lena; Kaler, Stephen G; Pejler, Gunnar; Öhrvik, Helena

2017-12-15

Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation. Copyright © 2017 by The American Association of Immunologists, Inc.

Cadmium, copper, iron, and zinc concentrations in kidneys of grey wolves, Canis lupus, from Alaska, Idaho, Montana (USA) and the Northwest Territories (Canada).

PubMed

Hoffmann, S R; Blunck, S A; Petersen, K N; Jones, E M; Koval, J C; Misek, R; Frick, J A; Cluff, H D; Sime, C A; McNay, M; Beckman, K B; Atkinson, M W; Drew, M; Collinge, M D; Bangs, E E; Harper, R G

2010-11-01

Cadmium, copper, iron, and zinc levels were measured in the kidneys of 115 grey wolves (Canis lupus) from Idaho, Montana and Alaska (United States), and from the Northwest Territories (Canada). No significant differences in the levels of iron or copper were observed between locations, but wolf kidneys from more northern locations had significantly higher cadmium levels (Alaska > Northwest Territories > Montana ≈ Idaho), and wolves from Alaska showed significantly higher zinc than other locations. Additionally, female wolves in Alaska had higher iron levels than males, and adult wolves in Montana had higher copper levels than subadults.

Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation

PubMed Central

2014-01-01

Background Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM. Methods Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment. Cardiac function was analyzed in isolated-perfused working hearts, and myocardial total copper content measured by particle-induced x-ray emission spectroscopy (PIXE) coupled with Rutherford backscattering spectrometry (RBS). Quantitative expression (mRNA and protein) and/or activity of key proteins that mediate LV-tissue-copper binding and transport, were analyzed by combined RT-qPCR, western blotting, immunofluorescence microscopy, and enzyme activity assays. Statistical analysis was performed using Student’s t-tests or ANOVA and p-values of < 0.05 have been considered significant. Results Left-ventricular (LV) copper levels and function were severely depressed in rats following 16-weeks’ diabetes, but both were unexpectedly normalized 8-weeks after treatment with TETA was instituted. Localized myocardial copper deficiency was accompanied by decreased expression and increased polymerization of the copper-responsive transition-metal-binding metallothionein proteins (MT1/MT2), consistent with impaired anti-oxidant defences and elevated susceptibility to pro-oxidant stress. Levels of the high-affinity copper transporter-1 (CTR1) were depressed in diabetes, consistent with impaired membrane copper uptake, and were not modified by TETA which, contrastingly, renormalized myocardial copper and increased levels and cell-membrane localization of the low-affinity copper transporter-2 (CTR2). Diabetes also lowered indexes of intracellular (IC) copper delivery via the copper chaperone for superoxide dismutase (CCS) to its target cuproenzyme, superoxide dismutase-1 (SOD1): this pathway was rectified by TETA treatment, which normalized SOD1 activity with consequent bolstering of anti-oxidant defenses. Furthermore, diabetes depressed levels of additional intracellular copper-transporting proteins, including antioxidant-protein-1 (ATOX1) and copper-transporting-ATPase-2 (ATP7B), whereas TETA elevated copper-transporting-ATPase-1 (ATP7A). Conclusions Myocardial copper deficiency and defective cellular copper transport/trafficking are revealed as key molecular defects underlying LV impairment in diabetes, and TETA-mediated restoration of copper regulation provides a potential new class of therapeutic molecules for DCM. PMID:24927960

Concentration dependent transcriptome responses of zebrafish embryos after exposure to cadmium, cobalt and copper.

PubMed

Sonnack, Laura; Klawonn, Thorsten; Kriehuber, Ralf; Hollert, Henner; Schäfers, Christoph; Fenske, Martina

2017-12-01

Environmental metals are known to cause harmful effects to fish of which many molecular mechanisms still require elucidation. Particularly concentration dependence of gene expression effects is unclear. Focusing on this matter, zebrafish embryo toxicity tests were used in combination with transcriptomics. Embryos were exposed to three concentrations of copper (CuSO 4 ), cadmium (CdCl 2 ) and cobalt (CoSO 4 ) from just after fertilization until the end of the 48hpf pre- and 96hpf post-hatch stage. The RNA was then analyzed on Agilent's Zebrafish (V3, 4×44K) arrays. Enrichment for GO terms of biological processes illustrated for cadmium that most affected GO terms were represented in all three concentrations, while for cobalt and copper most GO terms were represented in the lowest test concentration only. This suggested a different response to the non-essential cadmium than cobalt and copper. In cobalt and copper treated embryos, many developmental and cellular processes as well as the Wnt and Notch signaling pathways, were found significantly enriched. Also, different exposure concentrations affected varied functional networks. In contrast, the largest clusters of enriched GO terms for all three concentrations of cadmium included responses to cadmium ion, metal ion, xenobiotic stimulus, stress and chemicals. However, concentration dependence of mRNA levels was evident for several genes in all metal exposures. Some of these genes may be indicative of the mechanisms of action of the individual metals in zebrafish embryos. Real-time quantitative RT-PCR (qRT-PCR) verified the microarray data for mmp9, mt2, cldnb and nkx2.2a. Copyright © 2017 Elsevier Inc. All rights reserved.

Estimation of copper in saliva and areca nut products and its correlation with histological grades of oral submucous fibrosis.

PubMed

Mohammed, Faraz; Manohar, Vidya; Jose, Maji; Thapasum, Arishiya Fairozekhan; Mohamed, Shamaz; Shamaz, Bibi Halima; D'Souza, Neevan

2015-03-01

The purpose of this study was to estimate the copper levels in saliva of patients with oral submucous fibrosis (OSF) and different areca nut products and its correlation with different histological grades of OSF. The study comprised 60 individuals, 30 OSF patients and 30 non-OSF individuals. Unstimulated whole saliva was collected, and copper analysis was performed using colorimetric method. The commercial areca nut products used by the patients were acquired and subjected to copper analysis through the atomic absorption spectrophotometer method. Oral biopsies were performed for OSF patients for histopathological correlation. The mean salivary copper level was 27.023 μg/dl in OSF patients when compared with 8.393 μg/dl in non-OSF individuals (P < 0.005). The mean copper content in different areca nut products was 13.313 ppm (P < 0.005). Comparison of copper content in different areca nut products with salivary copper levels of OSF patients showed negative correlation (P < 0.853). Comparison of salivary copper levels between different histological grades of OSF yielded a statistically significant association between grades I and III (P < 0.005) and grades II and III OSF (P < 0.019). Comparison of copper content in areca nut products and different histological grades of OSF yielded weak negative statistical correlation (r = -0.116). Despite high copper content in areca nut products, the observations yielded a negative correlation with different histological grades of OSF. This further raises a doubt about the copper content in areca nut as an etiological factor for this crippling disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism.

PubMed

Khan, Husain Y; Zubair, Haseeb; Ullah, Mohd F; Ahmad, Aamir; Hadi, Sheikh M

2011-12-01

To account for the observed anticancer properties of plant polyphenols, we have earlier proposed a mechanism which involves the mobilization of endogenous copper ions by polyphenols leading to the generation of reactive oxygen species (ROS) that serve as proximal DNA cleaving agents and lead to cell death. Over the last decade we have proceeded to validate our hypothesis with considerable success. As a further confirmation of our hypothesis, in this paper we first show that oral administration of copper to rats leads to elevated copper levels in lymphocytes. When such lymphocytes with a copper overload were isolated and treated with polyphenols EGCG, genistein and resveratrol, an increased level of DNA breakage was observed. Further, preincubation of lymphocytes having elevated copper levels with the membrane permeable copper chelator neocuproine, resulted in inhibition of polyphenol induced DNA degradation. However, membrane impermeable chelator of copper bathocuproine, as well as iron and zinc chelators were ineffective in causing such inhibition in DNA breakage, confirming the involvement of endogenous copper in polyphenol induced cellular DNA degradation. It is well established that serum and tissue concentrations of copper are greatly increased in various malignancies. In view of this fact, the present results further confirm our earlier findings and strengthen our hypothesis that an important anticancer mechanism of plant polyphenols could be the mobilization of intracellular copper leading to ROS-mediated cellular DNA breakage. In this context, it may be noted that cancer cells are under considerable oxidative stress and increasing such stress to cytotoxic levels could be a successful anticancer approach.

Molecular Mediators Governing Iron-Copper Interactions

PubMed Central

Gulec, Sukru; Collins, James F.

2015-01-01

Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states. PMID:24995690

Low copper and high manganese levels in prion protein plaques

USGS Publications Warehouse

Johnson, Christopher J.; Gilbert, P.U.P.A.; Abrecth, Mike; Baldwin, Katherine L.; Russell, Robin E.; Pedersen, Joel A.; McKenzie, Debbie

2013-01-01

Accumulation of aggregates rich in an abnormally folded form of the prion protein characterize the neurodegeneration caused by transmissible spongiform encephalopathies (TSEs). The molecular triggers of plaque formation and neurodegeneration remain unknown, but analyses of TSE-infected brain homogenates and preparations enriched for abnormal prion protein suggest that reduced levels of copper and increased levels of manganese are associated with disease. The objectives of this study were to: (1) assess copper and manganese levels in healthy and TSE-infected Syrian hamster brain homogenates; (2) determine if the distribution of these metals can be mapped in TSE-infected brain tissue using X-ray photoelectron emission microscopy (X-PEEM) with synchrotron radiation; and (3) use X-PEEM to assess the relative amounts of copper and manganese in prion plaques in situ. In agreement with studies of other TSEs and species, we found reduced brain levels of copper and increased levels of manganese associated with disease in our hamster model. We also found that the in situ levels of these metals in brainstem were sufficient to image by X-PEEM. Using immunolabeled prion plaques in directly adjacent tissue sections to identify regions to image by X-PEEM, we found a statistically significant relationship of copper-manganese dysregulation in prion plaques: copper was depleted whereas manganese was enriched. These data provide evidence for prion plaques altering local transition metal distribution in the TSE-infected central nervous system.

Structural characterization of two solvates of a luminescent copper(II) bis­(pyridine)-substituted benzimidazole complex

PubMed Central

DeStefano, Matthew R.; Lewis, Robert A.

2017-01-01

Copper(II) complexes of benzimidazole are known to exhibit biological activity that makes them of inter­est for chemotherapeutic and other pharmaceutical uses. The complex bis­(acetato-κO){5,6-dimethyl-2-(pyridin-2-yl)-1-[(pyridin-2-yl)meth­yl]-1H-benzimidazole-κ2 N 2,N 3}copper(II), has been prepared. The absorption spectrum has features attributed to intra­ligand and ligand-field transitions and the complex exhibits ligand-centered room-temperature luminescence in solution. The aceto­nitrile monosolvate, [Cu(C2H3O2)2(C20H18N4)]·C2H3N (1), and the ethanol hemisolvate, [Cu(C2H3O2)2(C20H18N4)]·0.5C2H6O (2), have been structurally characterized. Compound 2 has two copper(II) complexes in the asymmetric unit. In both 1 and 2, distorted square-planar N2O2 coordination geometries are observed and the Cu—N(Im) bond distance is slightly shorter than the Cu—N(py) bond distance. Inter­molecular π–π inter­actions are found in 1 and 2. A weak C—H⋯π inter­action is observed in 1. PMID:29152336

The Features of Copper Metabolism in the Rat Liver during Development

PubMed Central

2015-01-01

Strong interest in copper homeostasis is due to the fact that copper is simultaneously a catalytic co-factor of the vital enzymes, a participant in signaling, and a toxic agent provoking oxidative stress. In mammals, during development copper metabolism is conformed to two types. In embryonic type copper metabolism (ETCM), newborns accumulate copper to high level in the liver because its excretion via bile is blocked; and serum copper concentration is low because ceruloplasmin (the main copper-containing protein of plasma) gene expression is repressed. In the late weaning, the ETCM switches to the adult type copper metabolism (ATCM), which is manifested by the unlocking of copper excretion and the induction of ceruloplasmin gene activity. The considerable progress has been made in the understanding of the molecular basis of copper metabolic turnover in the ATCM, but many aspects of the copper homeostasis in the ETCM remain unclear. The aim of this study was to investigate the copper metabolism during transition from the ETCM (up to 12-days-old) to the ATCM in the rats. It was shown that in the liver, copper was accumulated in the nuclei during the first 5 days of life, and then it was re-located to the mitochondria. In parallel with the mitochondria, copper bulk bound with cytosolic metallothionein was increased. All compartments of the liver cells rapidly lost most of their copper on the 13th day of life. In newborns, serum copper concentration was low, and its major fraction was associated with holo-Cp, however, a small portion of copper was bound to extracellular metallothionein and a substance that was slowly eluted during gel-filtration. In adults, serum copper concentration increased by about a factor of 3, while metallothionein-bound copper level decreased by a factor of 2. During development, the expression level of Cp, Sod1, Cox4i1, Atp7b, Ctr1, Ctr2, Cox17, and Ccs genes was significantly increased, and metallothionein was decreased. Atp7a gene’s activity was fully repressed. The copper routes in newborns are discussed. PMID:26474410

Combining -Omics to Unravel the Impact of Copper Nutrition on Alfalfa (Medicago sativa) Stem Metabolism.

PubMed

Printz, Bruno; Guerriero, Gea; Sergeant, Kjell; Audinot, Jean-Nicolas; Guignard, Cédric; Renaut, Jenny; Lutts, Stanley; Hausman, Jean-Francois

2016-02-01

Copper can be found in the environment at concentrations ranging from a shortage up to the threshold of toxicity for plants, with optimal growth conditions situated in between. The plant stem plays a central role in transferring and distributing minerals, water and other solutes throughout the plant. In this study, alfalfa is exposed to different levels of copper availability, from deficiency to slight excess, and the impact on the metabolism of the stem is assessed by a non-targeted proteomics study and by the expression analysis of key genes controlling plant stem development. Under copper deficiency, the plant stem accumulates specific copper chaperones, the expression of genes involved in stem development is decreased and the concentrations of zinc and molybdenum are increased in comparison with the optimum copper level. At the optimal copper level, the expression of cell wall-related genes increases and proteins playing a role in cell wall deposition and in methionine metabolism accumulate, whereas copper excess imposes a reduction in the concentration of iron in the stem and a reduced abundance of ferritins. Secondary ion mass spectrometry (SIMS) analysis suggests a role for the apoplasm as a copper storage site in the case of copper toxicity. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

Combining -Omics to Unravel the Impact of Copper Nutrition on Alfalfa (Medicago sativa) Stem Metabolism

PubMed Central

Printz, Bruno; Guerriero, Gea; Sergeant, Kjell; Audinot, Jean-Nicolas; Guignard, Cédric; Renaut, Jenny; Lutts, Stanley; Hausman, Jean-Francois

2016-01-01

Copper can be found in the environment at concentrations ranging from a shortage up to the threshold of toxicity for plants, with optimal growth conditions situated in between. The plant stem plays a central role in transferring and distributing minerals, water and other solutes throughout the plant. In this study, alfalfa is exposed to different levels of copper availability, from deficiency to slight excess, and the impact on the metabolism of the stem is assessed by a non-targeted proteomics study and by the expression analysis of key genes controlling plant stem development. Under copper deficiency, the plant stem accumulates specific copper chaperones, the expression of genes involved in stem development is decreased and the concentrations of zinc and molybdenum are increased in comparison with the optimum copper level. At the optimal copper level, the expression of cell wall-related genes increases and proteins playing a role in cell wall deposition and in methionine metabolism accumulate, whereas copper excess imposes a reduction in the concentration of iron in the stem and a reduced abundance of ferritins. Secondary ion mass spectrometry (SIMS) analysis suggests a role for the apoplasm as a copper storage site in the case of copper toxicity. PMID:26865661

Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes.

PubMed

Wei, Xiang-Bo; Guo, Liang; Liu, Yang; Zhou, Shui-Rong; Liu, Yuan; Dou, Xin; Du, Shao-Yue; Ding, Meng; Peng, Wan-Qiu; Qian, Shu-Wen; Huang, Hai-Yan; Tang, Qi-Qun

2017-09-23

Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM. Copyright © 2017. Published by Elsevier Inc.

Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice

PubMed Central

Matak, Pavle; Zumerle, Sara; Mastrogiannaki, Maria; El Balkhi, Souleiman; Delga, Stephanie; Mathieu, Jacques R. R.; Canonne-Hergaux, François; Poupon, Joel; Sharp, Paul A.; Vaulont, Sophie; Peyssonnaux, Carole

2013-01-01

Iron and copper are essential trace metals, actively absorbed from the proximal gut in a regulated fashion. Depletion of either metal can lead to anemia. In the gut, copper deficiency can affect iron absorption through modulating the activity of hephaestin - a multi-copper oxidase required for optimal iron export from enterocytes. How systemic copper status regulates iron absorption is unknown. Mice were subjected to a nutritional copper deficiency-induced anemia regime from birth and injected with copper sulphate intraperitoneally to correct the anemia. Copper deficiency resulted in anemia, increased duodenal hypoxia and Hypoxia inducible factor 2α (HIF-2α) levels, a regulator of iron absorption. HIF-2α upregulation in copper deficiency appeared to be independent of duodenal iron or copper levels and correlated with the expression of iron transporters (Ferroportin - Fpn, Divalent Metal transporter – Dmt1) and ferric reductase – Dcytb. Alleviation of copper-dependent anemia with intraperitoneal copper injection resulted in down regulation of HIF-2α-regulated iron absorption genes in the gut. Our work identifies HIF-2α as an important regulator of iron transport machinery in copper deficiency. PMID:23555700

The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis in Caenorhabditis elegans*♦

PubMed Central

Chun, Haarin; Sharma, Anuj Kumar; Lee, Jaekwon; Chan, Jefferson; Jia, Shang; Kim, Byung-Eun

2017-01-01

Copper plays key catalytic and regulatory roles in biochemical processes essential for normal growth, development, and health. Defects in copper metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular disease and are associated with other pathophysiological states. Consequently, it is critical to understand the mechanisms by which organisms control the acquisition, distribution, and utilization of copper. The intestinal enterocyte is a key regulatory point for copper absorption into the body; however, the mechanisms by which intestinal cells transport copper to maintain organismal copper homeostasis are poorly understood. Here, we identify a mechanism by which organismal copper homeostasis is maintained by intestinal copper exporter trafficking that is coordinated with extraintestinal copper levels in Caenorhabditis elegans. Specifically, we show that CUA-1, the C. elegans homolog of ATP7A/B, localizes to lysosome-like organelles (gut granules) in the intestine under copper overload conditions for copper detoxification, whereas copper deficiency results in a redistribution of CUA-1 to basolateral membranes for copper efflux to peripheral tissues. Worms defective in gut granule biogenesis exhibit defects in copper sequestration and increased susceptibility to toxic copper levels. Interestingly, however, a splice isoform CUA-1.2 that lacks a portion of the N-terminal domain is targeted constitutively to the basolateral membrane irrespective of dietary copper concentration. Our studies establish that CUA-1 is a key intestinal copper exporter and that its trafficking is regulated to maintain systemic copper homeostasis. C. elegans could therefore be exploited as a whole-animal model system to study regulation of intra- and intercellular copper trafficking pathways. PMID:27881675

Response to excess copper in the hyperthermophile Sulfolobus solfataricus strain 98/2

PubMed Central

Villafane, Aramis; Voskoboynik, Yekaterina; Cuebas, Mariola; Ruhl, Ilona; Bini, Elisabetta

2009-01-01

Copper is an essential micronutrient, but toxic in excess. Sulfolobus solfataricus cells have the ability to adapt to fluctuations of copper levels in their external environment. To better understand the molecular mechanism behind the organismal response to copper, the expression of the cluster of genes copRTA, which encodes the copper-responsive transcriptional regulator CopR, the copper-binding protein CopT, and CopA, has been investigated and the whole operon has been shown to be cotranscribed at low levels from the copR promoter under all conditions, whereas increased transcription from the copTA promoter occurs in the presence of excess copper. Furthermore, the expression of the copper-transporting ATPase CopA over a 27-hour interval has been monitored by quantitative real-time RT-PCR and compared to the pattern of cellular copper accumulation, as determined in a parallel analysis by Inductively Coupled Plasma Optical Emission spectrometry (ICP-OES). The results provide the basis for a model of the molecular mechanisms of copper homeostasis in Sulfolobus, which relies on copper efflux and sequestration. PMID:19427833

Dietary copper: a novel predisposing factor for oral submucous fibrosis?

PubMed

Arakeri, Gururaj; Brennan, Peter A

2013-03-01

Oral submucous fibrosis (OSMF) is known devastating disorder commonly seen in South Asian developing countries. It is directly linked to areca nut chewing and the contents of areca are subjected to multitude of investigations. Among all the contents of areca nut, the copper element has been extensively studied. Most of the published studies have validated its association with OSMF because of its local action. In this paper we postulate a novel biological pathway through which copper is thought to predispose oral mucosa to OSMF. The hypothesis is instructive in explaining various unexplored aspects of the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

The interaction of copper ions with Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli: an X-ray absorption near-edge structure (XANES) spectroscopy study.

PubMed

Zanzen, Ulrike; Bovenkamp-Langlois, Lisa; Klysubun, Wantana; Hormes, Josef; Prange, Alexander

2018-04-01

The antimicrobial properties of copper ions have been known for a long time. However, the exact mechanism of action of the transition metal on microorganisms has long been unclear. X-ray absorption near-edge structure (XANES) spectroscopy at the Cu K edge allows the determination of copper speciation in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa that have been treated with Cu(II) and Cu(I) solutions. The death/inactivation of the bacteria was observed using plate counting and light microscopy. The Cu K-XANES spectra of the two Gram-negative bacteria are different than those of the Gram-positive strain. The results clearly show that the Cu + -S bond contributes to the antibacterial activity of copper, as in the case of silver. The detailed evaluation of the differentiated absorption spectra shows that Cu + (not Cu 2+ ) is the dominant ion that binds to the bacteria. Because Cu + is not the most common copper ion, copper is not as effective an antibacterial agent as silver, whose common valency is actually + 1. Any reaction of copper with phosphorus from the bacteria can be excluded after the evaluation of the absorption spectra.

Galvanic zinc-copper microparticles inhibit melanogenesis via multiple pigmentary pathways.

PubMed

Won, Yen-Kim; Lin, Connie B; Seiberg, Miri; Chen, Nannan; Hu, Yaping; Rossetti, Dianne; Saliou, Claude; Loy, Chong-Jin

2014-01-01

The endogenous electrical field of human skin plays an important role in many skin functions. However, the biological effects and mechanism of action of externally applied electrical stimulation on skin remain unclear. Recent study showed that galvanic zinc-copper microparticles produce electrical stimulation and reduce inflammatory and immune responses in intact skin, suggesting the important role of electrical stimulation in non-wounded skin. The objective of this study is to investigate the biological effect of galvanic zinc-copper microparticles on skin pigmentation. Our findings showed that galvanic zinc-copper microparticles inhibited melanogenesis in a human melanoma cell line (MNT-1), human keratinocytes and melanoma cells co-cultures, and in pigmented epidermal equivalents. Treatment of galvanic zinc-copper microparticles inhibited melanogenesis by reducing the promoter transactivation of tyrosinase and tyrosinase-related protein-1 in human melanoma cells. In a co-culture Transwell system of keratinocytes and melanoma cells, galvanic zinc-copper microparticles reduced melanin production via downregulation of endothelin-1 secretion from keratinocytes and reduced tyrosinase gene expression in melanoma cells. In addition, exposure of pigmented epidermal equivalents to galvanic zinc-copper microparticles resulted in reduced melanin deposition. In conclusion, our data demonstrated for the first time that galvanic zinc-copper microparticles reduced melanogenesis in melanoma cells and melanin deposition in pigmented epidermal equivalents by affecting multiple pigmentary pathways.

Copper Tolerance and Biosorption of Saccharomyces cerevisiae during Alcoholic Fermentation

PubMed Central

Liu, Ling-ling; Jia, Bo; Zhao, Fang; Huang, Wei-dong; Zhan, Ji-cheng

2015-01-01

At high levels, copper in grape mash can inhibit yeast activity and cause stuck fermentations. Wine yeast has limited tolerance of copper and can reduce copper levels in wine during fermentation. This study aimed to understand copper tolerance of wine yeast and establish the mechanism by which yeast decreases copper in the must during fermentation. Three strains of Saccharomyces cerevisiae (lab selected strain BH8 and industrial strains AWRI R2 and Freddo) and a simple model fermentation system containing 0 to 1.50 mM Cu2+ were used. ICP-AES determined Cu ion concentration in the must decreasing differently by strains and initial copper levels during fermentation. Fermentation performance was heavily inhibited under copper stress, paralleled a decrease in viable cell numbers. Strain BH8 showed higher copper-tolerance than strain AWRI R2 and higher adsorption than Freddo. Yeast cell surface depression and intracellular structure deformation after copper treatment were observed by scanning electron microscopy and transmission electron microscopy; electronic differential system detected higher surface Cu and no intracellular Cu on 1.50 mM copper treated yeast cells. It is most probably that surface adsorption dominated the biosorption process of Cu2+ for strain BH8, with saturation being accomplished in 24 h. This study demonstrated that Saccharomyces cerevisiae strain BH8 has good tolerance and adsorption of Cu, and reduces Cu2+ concentrations during fermentation in simple model system mainly through surface adsorption. The results indicate that the strain selected from China’s stress-tolerant wine grape is copper tolerant and can reduce copper in must when fermenting in a copper rich simple model system, and provided information for studies on mechanisms of heavy metal stress. PMID:26030864

The prevalence of low serum zinc and copper levels and dietary habits associated with serum zinc and copper in 12- to 36-month-old children from low-income families at risk for iron deficiency.

PubMed

Schneider, Julie M; Fujii, Mary L; Lamp, Catherine L; Lönnerdal, Bo; Zidenberg-Cherr, Sheri

2007-11-01

Iron and zinc share common food sources, and children at risk of iron deficiency may also develop zinc deficiency. We determined the prevalence of zinc and copper deficiency and examined factors associated with serum zinc and copper in young children from low-income families at risk of iron deficiency. A cross-sectional study design was used to assess serum zinc and copper, along with an interview-assisted survey to assess factors associated with serum zinc and copper in a convenience sample. Participants were 435 children aged 12 to 36 months recruited from select clinics of the Special Supplemental Nutrition Program for Women, Infants, and Children in Contra Costa and Tulare Counties, California. Frequencies were used to report prevalence. Multiple linear regressions were conducted to examine factors associated with serum zinc and copper, controlling for age, sex, and ethnicity. The prevalence of low serum zinc level (<70 microg/dL [<10.7 micromol/L]) was 42.8%, and low serum copper level (<90 microg/dL [<14.2 micromol/L]) was <1%. Mean+/-standard deviation of serum copper was 150+/-22 microg/dL (23.6+/-3.5 micromol/L) and 140+/-24 microg/dL (22.1+/-3.8 micromol/L) for anemic and non-anemic children, respectively (t test, P=0.026). In multiple linear regression consumption of sweetened beverages was negatively associated with serum zinc level, and consumption of >15 g/day meat was positively associated with serum zinc level, whereas current consumption of breast milk and >15 g/day beans were positively associated with serum copper level. The prevalence of low serum zinc concentration in the sample was high, and warrants further investigation amongst vulnerable populations.

How do anthropogenic contaminants (ACs) affect behaviour? Multi-level analysis of the effects of copper on boldness in hermit crabs.

PubMed

White, Stephen J; Briffa, Mark

2017-02-01

Natural animal populations are increasingly exposed to human impacts on the environment, which could have consequences for their behaviour. Among these impacts is exposure to anthropogenic contaminants. Any environmental variable that influences internal state could impact behaviour across a number of levels: at the sample mean, at the level of among-individual differences in behaviour ('animal personality') and at the level of within-individual variation in behaviour (intra-individual variation, 'IIV'). Here we examined the effect of exposure to seawater-borne copper on the startle response behaviour of European hermit crabs, Pagurus bernhardus across these levels. Copper exposure rapidly led to longer startle responses on average, but did not lead to any change in repeatability indicating that individual differences were present and equally consistent in the presence and absence of copper. There was no strong evidence that copper exposure led to changes in IIV. Our data show that exposure to copper for 1 week produces sample mean level changes in the behaviour of hermit crabs. However, there is no evidence that this exposure led to changes in repeatability through feedback loops.

DJ-1 Is a Copper Chaperone Acting on SOD1 Activation*

PubMed Central

Girotto, Stefania; Cendron, Laura; Bisaglia, Marco; Tessari, Isabella; Mammi, Stefano; Zanotti, Giuseppe; Bubacco, Luigi

2014-01-01

Lack of oxidative stress control is a common and often prime feature observed in many neurodegenerative diseases. Both DJ-1 and SOD1, proteins involved in familial Parkinson disease and amyotrophic lateral sclerosis, respectively, play a protective role against oxidative stress. Impaired activity and modified expression of both proteins have been observed in different neurodegenerative diseases. A potential cooperative action of DJ-1 and SOD1 in the same oxidative stress response pathway may be suggested based on a copper-mediated interaction between the two proteins reported here. To investigate the mechanisms underlying the antioxidative function of DJ-1 in relation to SOD1 activity, we investigated the ability of DJ-1 to bind copper ions. We structurally characterized a novel copper binding site involving Cys-106, and we investigated, using different techniques, the kinetics of DJ-1 binding to copper ions. The copper transfer between the two proteins was also examined using both fluorescence spectroscopy and specific biochemical assays for SOD1 activity. The structural and functional analysis of the novel DJ-1 copper binding site led us to identify a putative role for DJ-1 as a copper chaperone. Alteration of the coordination geometry of the copper ion in DJ-1 may be correlated to the physiological role of the protein, to a potential failure in metal transfer to SOD1, and to successive implications in neurodegenerative etiopathogenesis. PMID:24567322

Transcriptional response of Erwinia amylovora to copper shock: in vivo role of the copA gene.

PubMed

Águila-Clares, Begoña; Castiblanco, Luisa F; Quesada, José Miguel; Penyalver, Ramón; Carbonell, Juan; López, María M; Marco-Noales, Ester; Sundin, George W

2018-01-01

Fire blight is a devastating plant disease caused by the bacterium Erwinia amylovora, and its control is frequently based on the use of copper-based compounds whose mechanisms of action are not well known. Consequently, in this article, we investigate the response of E. amylovora to copper shock by a whole-genome microarray approach. Transcriptional analyses showed that, in the presence of copper, 23 genes were increased in expression; these genes were classified mainly into the transport and stress functional categories. Among them, the copA gene was strongly induced and regulated in a finely tuned manner by copper. Mutation of copA, soxS, arcB, yjcE, ygcF, yhhQ, galF and EAM_3469 genes revealed that tolerance to copper in E. amylovora can be achieved by complex physiological mechanisms, including: (i) the control of copper homeostasis through, at least, the extrusion of Cu(I) by a P-type ATPase efflux pump CopA; and (ii) the overcoming of copper toxicity caused by oxidative stress by the expression of several reactive oxygen species (ROS)-related genes, including the two major transcriptional factors SoxS and ArcB. Furthermore, complementation analyses demonstrated the important role of copA for copper tolerance in E. amylovora, not only in vitro, but also in inoculated pear shoots. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Impact on sediments and water by release of copper from chalcopyrite bearing rock due to acidic mine drainage

NASA Astrophysics Data System (ADS)

Shukla, Anoop Kant; Pradhan, Manoj; Tiwari, Onkar Nath

2018-04-01

Mining activity causes transition of rock-mass from its original position in earth into open environment. The action of environmental elements such air, water, microorganisms leads to oxidation of minerals which constitute the rock. The oxidation of sulphide minerals in presence of moisture releases acidic mine discharge (AMD). The acidic nature of AMD causes leaching of metals from rock minerals. Dissolution of other minerals may occur upon reaction with AMD. Chalcopyrite (CuFeS2) undergoes oxidation in acidic condition releasing copper among other products. This study reveals contamination of copper in sediment samples and seepage water from the tailing dam of a large copper project in located in central India. Elevation was studied using GIS to ascertain to the topographic elevation of tailing dam area. It was located at relatively high altitude causing seepage to flow away from tailing dam. The seepage water from tailing dam was found to be acidic with mean pH value of 4.0 and elevated copper content. Similarly, sediments from seepage water flow displayed elevated copper concentration. The copper concentration in seepage water was found with a mean value of 10.73 mg/l. The sediments from seepage water flow also displayed elevated copper concentration with mean value of 26.92 g/kg. This indicates impact on sediments by release of copper due to acidic mine drainage.

Importance of Pipe Deposits to Lead and Copper Rule Compliance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schock, Michael R.; Cantor, Abigail F.; Triantafyllidou, Simoni

When Madison, Wis., exceeded the lead action level in 1992, residential and off-line tests suggested that lead release into the water was more complex than a lead solubility mechanism. Scale analyses (color and texture as well as mineralogical and elemental composition) of five excavated lead service lines (LSLs) revealed that accumulation of manganese (and iron) onto pipe walls had implications for lead corrosion by providing a high-capacity sink for lead. Manganese that accumulated from source well water onto pipe scales (up to 10% by weight of scale composition) served to capture and eventually transport lead to consumer taps. In addition,more » manganese sometimes obstructed the predominance of an insoluble (and thus potentially protective) plattnerite [Pb(IV) solid] scale layer. Full LSL replacement in Madison achieved Lead and Copper Rule compliance and a major reduction in lead contamination and exposure, supplemented by unidirectional flushing of water mains and manganese control in the source well water.« less

Studies of copper and gold vapour lasers

NASA Astrophysics Data System (ADS)

Clark, Graeme Lawrence

The work described in this thesis covers various aspects of pulsed copper and gold vapour lasers. The work is divided into four main parts : a computer model of the kinetics of the copper vapour laser discharge; construction and characterization of a copper vapour laser and a gold vapour laser system (to be used for photodynamic cancer treatment); analysis of the thermal processes occurring in the various forms of thermal insulation used in these lasers; and studies of the use of metal walls to confine a discharge plasma. The results of this work were combined in the design of the first copper vapour laser to use metal rather than an electrically insulating ceramic material for confinement of the discharge plasma. Laser action in copper vapour has been achieved in a number of metal-walled designs, with continuous lengths of metal ranging from 30 mm, in a segmented design, to 400 mm, where the discharge plasma was confined by two molybdenum tubes of this length. A theoretical explanation of the behaviour of plasmas in metal-walled discharge vessels is described.

Does Dietary Copper Supplementation enhance or diminish PCB126 Toxicity in Rodent Liver?

PubMed Central

Lai, Ian K.; Klaren, William D.; Li, Miao; Wels, Brian; Simmons, Donald L.; Olivier, Alicia K.; Haschek, Wanda M.; Wang, Kai; Ludewig, Gabriele; Robertson, Larry W.

2013-01-01

Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins. However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals. Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers. This is accompanied by biochemical and toxic changes. To assess the involvement of copper in PCB toxicity, male Sprague Dawley rats were fed an AIN-93G diet with differing dietary copper levels: low (2 ppm), adequate (6 ppm), and high (10 ppm). After three weeks, rats from each group were given a single ip injection of corn oil (control), 1, or 5 μmol/kg body weight PCB126. Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated. Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin. In the livers of PCB126-treated rats the hallmark signs of AhR activation were present, including increased cytochrome P-450 and lipid levels, and decreased glutathione. In addition a doubling of hepatic copper levels was seen and overall metals homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc and iron. Expression of key metalloproteins was either decreased (cytochrome c oxidase), unchanged (ceruloplasmin and CuZnSOD) or increased (tyrosinase, metallothionein 1 and 2) with exposure to PCB126. Increases in metallothionein may contribute/reflect the increased copper seen. Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126. PCB126 toxicity, i.e. oxidative stress and steatosis, is clearly associated with disturbed metals homeostasis. Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists. PMID:23527585

Cytoplasmic CopZ-Like Protein and Periplasmic Rusticyanin and AcoP Proteins as Possible Copper Resistance Determinants in Acidithiobacillus ferrooxidans ATCC 23270

PubMed Central

Navarro, Claudio A.; von Bernath, Diego; Martínez-Bussenius, Cristóbal; Castillo, Rodrigo A.

2015-01-01

Acidophilic organisms, such as Acidithiobacillus ferrooxidans, possess high-level resistance to copper and other metals. A. ferrooxidans contains canonical copper resistance determinants present in other bacteria, such as CopA ATPases and RND efflux pumps, but these components do not entirely explain its high metal tolerance. The aim of this study was to find other possible copper resistance determinants in this bacterium. Transcriptional expression of A. ferrooxidans genes coding for a cytoplasmic CopZ-like copper-binding chaperone and the periplasmic copper-binding proteins rusticyanin and AcoP, which form part of an iron-oxidizing supercomplex, was found to increase when the microorganism was grown in the presence of copper. All of these proteins conferred more resistance to copper when expressed heterologously in a copper-sensitive Escherichia coli strain. This effect was absent when site-directed-mutation mutants of these proteins with altered copper-binding sites were used in this metal sensitivity assay. These results strongly suggest that the three copper-binding proteins analyzed here are copper resistance determinants in this extremophile and contribute to the high-level metal resistance of this industrially important biomining bacterium. PMID:26637599

Evaluation of toxic and interactive toxic effects of three agrochemicals and copper using a battery of microbiotests.

PubMed

Kungolos, A; Emmanouil, C; Tsiridis, V; Tsiropoulos, N

2009-08-01

Three commonly used test organisms of different trophic levels (Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna) were exposed to selected agrochemicals (fosthiazate, metalaxyl-M, imidacloprid) and copper, in single doses or in binary mixtures. The toxicity of each single compound varied up to two orders of magnitude, depending on the test species examined. V. fischeri was the most sensitive test organism regarding fosthiazate and metalaxyl-M, indicating an IC(50) value of 0.20 mg/L (0.17-0.25 mg/L) and 0.88 mg/L (0.35-1.57 mg/L), respectively. Imidacloprid was the least toxic compound, indicating an EC(50) value on D. magna of 64.6 mg/L (43.3-122.5 mg/L) and an IC(50) value on V. fischeri of 226 mg/L (159-322 mg/L), while for imidacloprid at a concentration of 1000 mg/L the effect on P. subcapitata was lower than 50%. Copper was the most toxic compound towards all test organisms exhibiting the highest toxic effect on P. subcapitata, with an IC(50) value of 0.05 mg/L (0.003-0.008 mg/L). The toxic effects of the binary mixtures have been compared to the theoretically expected effect, resulting from a simple mathematical model based on the theory of probabilities. The independent action model was used in order to predict the theoretically expected effect. The interactive effects were mostly antagonistic or additive, while in few cases (interactive effects of metalaxyl-M and copper on V. fischeri) a synergistic mode of action was observed for some concentration combinations. Experiments showed that interactive effects of chemicals may vary depending on the test species used as well as on the chemicals and their respective concentrations. Although most of the concentrations of chemicals tested in this study are higher than the ones usually found in natural environment, the evaluation of their interactive toxic effects using a battery of bioassays may comprise a useful tool for the estimation of the environmental hazard of chemicals.

Determination of factors responsible for the bioweathering of copper minerals from organic-rich copper-bearing Kupferschiefer black shale.

PubMed

Włodarczyk, Agnieszka; Szymańska, Agata; Skłodowska, Aleksandra; Matlakowska, Renata

2016-04-01

The aim of this study was to investigate the bioweathering of copper minerals present in the alkaline, copper-bearing and organic-rich Kupferschiefer black shale through the action of a consortium of indigenous lithobiontic, heterotrophic, neutrophilic bacteria isolated from this sedimentary rock. The involvement of microorganisms in the direct/enzymatic bioweathering of fossil organic matter of the rock was confirmed. As a result of bacterial activity, a spectrum of various organic compounds such as urea and phosphoric acid tributyl ester were released from the rock. These compounds indirectly act on the copper minerals occurring in the rock and cause them to weather. This process was reflected in the mobilization of copper, iron and sulfur and in changes in the appearance of copper minerals observed under reflected light. The potential role of identified enzymes in biodegradation of fossil organic matter and role of organic compounds released from black shale as a result of this process in copper minerals weathering was discussed. The presented results provide a new insight into the role of chemical compounds released by bacteria during fossil organic matter bioweathering potentially important in the cycling of copper and iron deposited in the sedimentary rock. The originality of the described phenomenon lies in the fact that the bioweathering of fossil organic matter and, consequently, of copper minerals occur simultaneously in the same environment, without any additional sources of energy, electrons and carbon. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il; Shoshani-Dror, Dana; Guillemin, Claire

High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy.more » Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and oxidative stress of liver.« less

Acute toxicity to goldfish of mixtures of chloramines, copper, and linear alkylate sulfonate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, C.F.; McKee, J.A.

1980-01-01

The toxicity to goldfish (Carassius auratus) of mixtures of chloramines, copper, and linear alkylate sulfonate (LAS) was studied by continuous-flow toxicity tests during an exposure period of 96 hours. The individual toxicities of these three chemicals are either additive or synergistic in mixtures, depending on the rate of toxic action of the individual chemical, the toxicity ratio of the chemicals in the mixtures, and the concentration of the mixtures.

Gastrointestinal effects associated with soluble and insoluble copper in drinking water.

PubMed Central

Pizarro, F; Olivares, M; Araya, M; Gidi, V; Uauy, R

2001-01-01

The aim of this study was to determine whether total copper or soluble copper concentration is associated with gastrointestinal signs and symptoms. Forty-five healthy adult women (18-55 years of age), living in Santiago, Chile, ingested tap water with 5 mg/L of copper containing different ratios of soluble copper (copper sulfate) and insoluble copper (copper oxide) over a 9-week period. Three randomized sequences of the different copper ratios (0:5, 1:4, 2:3, 3:2, and 5:0 mg/L) were followed. Subjects recorded their water consumption and gastrointestinal symptoms daily on a special form. Mean water consumption was similar among groups. Serum copper levels, ceruloplasmin, and activities of liver enzymes were within normal limits. No differences were detected between the means of biochemical parameters at the beginning and at the end of the study. Twenty subjects presented gastrointestinal disturbances at least once during the study, 9 suffered diarrhea (with or without abdominal pain and vomiting), and the other 11 subjects reported abdominal pain, nausea, or vomiting. No differences were found in incidence of abdominal pain, nausea, vomiting, and diarrhea regardless of the ratio of copper sulfate to copper oxide. In conclusion, both copper sulfate (a soluble compound) and copper oxide (an insoluble compound) have comparable effects on the induction of gastrointestinal manifestations, implying that similar levels of ionic copper were present in the stomach. PMID:11673125

The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis in Caenorhabditis elegans.

PubMed

Chun, Haarin; Sharma, Anuj Kumar; Lee, Jaekwon; Chan, Jefferson; Jia, Shang; Kim, Byung-Eun

2017-01-06

Copper plays key catalytic and regulatory roles in biochemical processes essential for normal growth, development, and health. Defects in copper metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular disease and are associated with other pathophysiological states. Consequently, it is critical to understand the mechanisms by which organisms control the acquisition, distribution, and utilization of copper. The intestinal enterocyte is a key regulatory point for copper absorption into the body; however, the mechanisms by which intestinal cells transport copper to maintain organismal copper homeostasis are poorly understood. Here, we identify a mechanism by which organismal copper homeostasis is maintained by intestinal copper exporter trafficking that is coordinated with extraintestinal copper levels in Caenorhabditis elegans Specifically, we show that CUA-1, the C. elegans homolog of ATP7A/B, localizes to lysosome-like organelles (gut granules) in the intestine under copper overload conditions for copper detoxification, whereas copper deficiency results in a redistribution of CUA-1 to basolateral membranes for copper efflux to peripheral tissues. Worms defective in gut granule biogenesis exhibit defects in copper sequestration and increased susceptibility to toxic copper levels. Interestingly, however, a splice isoform CUA-1.2 that lacks a portion of the N-terminal domain is targeted constitutively to the basolateral membrane irrespective of dietary copper concentration. Our studies establish that CUA-1 is a key intestinal copper exporter and that its trafficking is regulated to maintain systemic copper homeostasis. C. elegans could therefore be exploited as a whole-animal model system to study regulation of intra- and intercellular copper trafficking pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants.

PubMed

Talat, Mohamed A; Ahmed, Anwar; Mohammed, Lamia

2015-10-01

To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1 ± 3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. The mean zinc level was 60.1 ± 22.6 ug/dl in the cases, and 102.1 ± 18 ug/dl in the controls (p<0.001). The mean copper level was 180.1 ± 32.4 ug/dl in cases compared with 114.5 ± 18.5 ug/dl in controls (p<0.001). Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients.

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

PubMed Central

Talat, Mohamed A.; Ahmed, Anwar; Mohammed, Lamia

2015-01-01

Objective: To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. Methods: A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1±3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. Results: The mean zinc level was 60.1±22.6 ug/dl in the cases, and 102.1±18 ug/dl in the controls (p<0.001). The mean copper level was 180.1±32.4 ug/dl in cases compared with 114.5±18.5 ug/dl in controls (p<0.001). Conclusion: Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients. PMID:26492112

Copper-granule-catalyzed microwave-assisted click synthesis of polyphenol dendrimers.

PubMed

Lee, Choon Young; Held, Rich; Sharma, Ajit; Baral, Rom; Nanah, Cyprien; Dumas, Dan; Jenkins, Shannon; Upadhaya, Samik; Du, Wenjun

2013-11-15

Syringaldehyde- and vanillin-based antioxidant dendrimers were synthesized via microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated dendrimers. To produce copper-free antioxidant dendrimers for biological applications, Cu(I) was substituted with copper granules. Copper granules were ineffective at both room temperature and under reflux conditions (<5% yield). However, they were an excellent catalyst when dendrimer synthesis was performed under microwave irradiation, giving yields up to 94% within 8 h. ICP-mass analysis of the antioxidant dendrimers obtained with this method showed virtually no copper contamination (9 ppm), which was the same as the background level. The synthesized antioxidants, free from copper contamination, demonstrated potent radical scavenging with IC50 values of less than 3 μM in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In comparison, dendrimers synthesized from Cu(I)-catalyzed click chemistry showed a high level of copper contamination (4800 ppm) and no detectable antioxidant activity.

CsoR Is Essential for Maintaining Copper Homeostasis in Mycobacterium tuberculosis

PubMed Central

Marcus, Sarah A.; Sidiropoulos, Sarah W.; Steinberg, Howard; Talaat, Adel M.

2016-01-01

Mycobacterium tuberculosis, a pathogen infecting one third of the world population, faces numerous challenges within the host, including high levels of copper. We have previously shown that M. tuberculosis CsoR is a copper inducible transcriptional regulator. Here we examined the hypothesis that csoR is necessary for maintaining copper homeostasis and surviving under various stress conditions. With an unmarked csoR knockout strain, we were able to characterize the role of csoR in M. tuberculosis as it faced copper and host stress. Growth under high levels of copper demonstrated that M. tuberculosis survives copper stress significantly better in the absence of csoR. Yet under minimal levels of copper, differential expression analysis revealed that the loss of csoR results in a cell wide hypoxia-type stress response with the induction of the DosR regulon. Despite the stress placed on M. tuberculosis by the loss of csoR, survival of the knockout strain was increased compared to wild type during the early chronic stages of mouse infection, suggesting that csoR could play an active role in modulating M. tuberculosis fitness within the host. Overall, analysis of CsoR provided an increased understanding of the M. tuberculosis copper response with implications for other intracellular pathogens harboring CsoR. PMID:26999439

Demystifying Controlling Copper Corrosion

EPA Science Inventory

The LCR systematically misses the highest health and corrosion risk sites for copper. Additionally, there are growing concerns for WWTP copper in sludges and discharge levels. There are many corrosion control differences between copper and lead. This talk explains the sometimes c...

New anionic carbosilane dendrons functionalized with a DO3A ligand at the focal point for the prevention of HIV-1 infection.

PubMed

Moreno, Silvia; Sepúlveda-Crespo, Daniel; de la Mata, F Javier; Gómez, Rafael; Muñoz-Fernández, Ma Ángeles

2017-10-01

Novel third-generation polyanionic carbosilane dendrons with sulfonate or carboxylate end-groups and functionalized with a DO3A ligand at the focal point, and their corresponding copper complexes, have been prepared as antiviral compounds to prevent HIV-1 infection. The topology enables the compound to have an excellent chelating agent, DO3A, while keeping anionic peripheral groups for a therapeutic action. In this study, the cytotoxicity and anti-HIV-1 abilities of carboxylate- (5) or sulfonate-terminated (6) dendrons containing DO3A and their copper complexes (7 or 8) were evaluated. All compounds showed low cytotoxicity and demonstrated potent and broad-spectrum anti-HIV-1 activity in vitro. We also assessed the mode of antiviral action on the inhibition of HIV-1 through a panel of different in vitro antiviral assays. Our results show that copper-free dendron 6 protects the epithelial monolayer from short-term cell disruption. Copper-free dendrons 5 and 6 exert anti-HIV-1 activity at an early stage of the HIV-1 lifecycle by binding to the envelope glycoproteins of HIV-1 and by interacting with the CD4 cell receptor and blocking the binding of gp120 to CD4, and consequently HIV-1 entry. These findings show that copper-free dendrons 5 and 6 have a high potency against HIV-1 infection, confirming their non-specific ability and suggesting that these compounds deserve further study as potential candidate microbicides to prevent HIV-1 transmission. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of some herbicides on the toxicity of certain molluscacides against Biomphalaria alexandrina snails.

PubMed

el-Fiki, S A; Mohamed, A M

1978-01-01

Studies dealing with the effect of some herbicides on the molluscicidal action of certain molluscicides against B. alexandrina have been carried out. In the first part of the study the toxicity of 3 molluscicides (Copper sulphate, Niclosamide and Frescon) and 3 herbicides (Gramaxone, Preforan and Treflan) was tested individually. Results indicated that the molluscicides were more potent than the herbicides. In the second part, snails were exposed for 24 hr to one of the tested herbicides using LC0 or (Sub. lethal conc) then the toxicity of molluscicides was determined among the same snails. Data indicated that pre-exposure to herbicides caused a synergistic action with copper sulphate, while with Niclosamide and Frescon marked antagonistic effect was observed. In the third part molluscicides and herbicides were mixed in different ratios (1:2, 1:1 and 2:1) and the toxicity of the mixtures was tested. A synergistic effect was observed in the case of copper sulphate plus various herbicides especially with Treflan at 1:2 ratio. With Niclosamide and Frescon slight antagonistic effect was detected.

Selenium, copper, zinc, iron levels and mortality in patients with sepsis and systemic inflammatory response syndrome in Western Black Sea Region, Turkey.

PubMed

Ayoglu, Hilal; Sezer, Ustun; Akin, Mehmet; Okyay, Dilek; Ayoglu, Ferruh; Can, Murat; Kucukosman, Gamze; Piskin, Ozcan; Aydin, Bengu; Cimencan, Murat; Gur, Abdullah; Turan, Isil

2016-04-01

To evaluate the changing levels of selenium, copper, zinc and iron in patients with sepsis and systemic inflammatory response syndrome and their influence on mortality. The prospective study was conducted at a tertiary care university hospital in Zonguldak city in the western Black Sea region of Turkey from January 2012 to December 2013, and comprised patients with sepsis and systemic inflammatory response syndrome. Blood samples were taken on 1st, 3rd, 5th and 7th days to measure serum selenium, copper, zinc and iron levels. Patients' demographic data, presence of additional diseases and mortality were recorded. Of the 57 patients, 28(49.1%) were female and 29(50.9%) were male, with an overall mean age of 60.3±19.4 years, mean height of 166.1±11.4cm, mean weight of 76.5±17.5kg. Copper and zinc levels were in the normal range, while selenium and iron levels were lower than the limit values at all measuring periods. There was no significant difference between first and other days in accordance with element levels (p>0.05). Baseline copper levels in patients with malignancy were lower than patients without malignancy (p< 0.05). In hypertensive patients, baseline copper levels were higher and 7th day levels were lower than non-hypertensive (p< 0.05). Baseline selenium levels of those who died were lower than the other patients (p< 0.05). Selenium and iron levels were decreased in patients with sepsis-systemic inflammatory response syndrome and copper levels were lower in patients with malignancy, hypertension and chronic obstructive pulmonary disease (p< 0.05). There was no change in zinc levels of the patients. Reduced basal selenium levels of patients with sepsis and systemic inflammatory response syndrome were associated with mortality.

The cardiac copper chaperone proteins Sco1 and CCS are up-regulated, but Cox 1 and Cox4 are down-regulated, by copper deficiency.

PubMed

Getz, Jean; Lin, Dingbo; Medeiros, Denis M

2011-10-01

Copper is ferried in a cell complexed to chaperone proteins, and in the heart much copper is required for cytochrome c oxidase (Cox). It is not completely understood how copper status affects the levels of these proteins. Here we determined if dietary copper deficiency could up- or down-regulate select copper chaperone proteins and Cox subunits 1 and 4 in cardiac tissue of rats. Sixteen weanling male Long-Evans rats were randomized into treatment groups, one group receiving a copper-deficient diet (<1 mg Cu/kg diet) and one group receiving a diet containing adequate copper (6 mg Cu/kg diet) for 5 weeks. Hearts were removed, weighed, and non-myofibrillar proteins separated to analyze for levels of CCS, Sco1, Ctr1, Cox17, Cox1, and Cox4 by SDS-PAGE and Western blotting. No changes were observed in the concentrations of CTR1 and Cox17 between copper-adequate and copper-deficient rats. CCS and Sco1 were up-regulated and Cox1 and Cox4 were both down-regulated as a result of copper deficiency. These data suggest that select chaperone proteins and may be up-regulated, and Cox1 and 4 down-regulated, by a dietary copper deficiency, whereas others appear not to be affected by copper status.

The effects of copper on blood and biochemical parameters of rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Dethloff, G.M.; Schlenk, D.; Khan, S.; Bailey, H.C.

1999-01-01

Metals are released into aquatic systems from many sources, often at sublethal concentrations. The effects of sublethal concentrations of metals on fish are not entirely understood. The objective of this study was to determine the hematological and biochemical effects of a range of copper concentrations (6.4, 16.0, 26.9 ??g Cu/L) on rainbow trout (Oncorhynchus mykiss) over a prolonged period of time. Trout were exposed to copper, and, at intervals of 3, 7, 14, and 21 days, selected parameters were evaluated. Hemoglobin, hematocrit, plasma glucose, and plasma cortisol levels were elevated in trout exposed to 26.9 ??g Cu/L at day 3 and then returned to levels comparable to control fish. Plasma protein and lactate levels were not significantly altered in trout from any copper treatment. Hepatic copper concentration and hepatic metallothionein mRNA expression were consistently elevated in trout exposed to 26.9 ??g Cu/L. Both of these parameters stabilized by day 3, with only hepatic copper concentration showing a further increase at day 21. Hepatic copper concentration and hepatic metallothionein mRNA expression appear to be robust indicators of copper exposure. Most blood-based parameters evaluated appear to be associated with a transitory, nonspecific stress response. The return of elevated hematological and biochemical parameters to control levels after 3 days and thestabilization of hepatic metallothionein mRNA expression and copper concentration over a similar time period suggested acclimation to dissolved copper at 26.9 ??g/L. Further analysis of the data on blood-based parameters indicated that certain parameters (hemoglobin, hematocrit, plasma glucose, plasma cortisol) may be useful in field monitoring.

Copper and zinc content in wild game shot with lead or non-lead ammunition – implications for consumer health protection

PubMed Central

Sommerfeld, Christine; Müller-Graf, Christine; Selhorst, Thomas; Greiner, Matthias; Gerofke, Antje; Ulbig, Ellen; Gremse, Carl; Spolders, Markus; Schafft, Helmut; Lahrssen-Wiederholt, Monika

2017-01-01

The aim of this study was to examine the contamination of game meat with copper and zinc and establish whether the use of alternative (non-lead) ammunition can lead to higher or unsafe levels of copper and zinc in the meat of roe deer, wild boar and red deer. The research project “Safety of game meat obtained through hunting” (LEMISI) was conducted in Germany with the purpose of examining the entry of lead as well as copper and zinc into the meat of hunted game when using either lead or non-lead ammunition. The outcome of this study shows that the usage of both lead-based ammunition and alternative non-lead ammunition results in the entry of copper and zinc into the edible parts of the game. Using non-lead ammunition does not entail dangerously elevated levels of copper and zinc, so replacing lead ammunition with alternative ammunition does not introduce a further health problem with regard to these metals. The levels of copper and zinc in game meat found in this study are in the range found in previous studies of game. The content of copper and zinc in game meat is also comparable to those regularly detected in meat and its products from livestock (pig, cattle, sheep) for which the mean human consumption rate is much higher. From the viewpoint of consumer health protection, the use of non-lead ammunition does not pose an additional hazard through copper and zinc contamination. A health risk due to the presence of copper and zinc in game meat at typical levels of consumer exposure is unlikely for both types of ammunition. PMID:28934259

Copper and zinc content in wild game shot with lead or non-lead ammunition - implications for consumer health protection.

PubMed

Schlichting, Daniela; Sommerfeld, Christine; Müller-Graf, Christine; Selhorst, Thomas; Greiner, Matthias; Gerofke, Antje; Ulbig, Ellen; Gremse, Carl; Spolders, Markus; Schafft, Helmut; Lahrssen-Wiederholt, Monika

2017-01-01

The aim of this study was to examine the contamination of game meat with copper and zinc and establish whether the use of alternative (non-lead) ammunition can lead to higher or unsafe levels of copper and zinc in the meat of roe deer, wild boar and red deer. The research project "Safety of game meat obtained through hunting" (LEMISI) was conducted in Germany with the purpose of examining the entry of lead as well as copper and zinc into the meat of hunted game when using either lead or non-lead ammunition. The outcome of this study shows that the usage of both lead-based ammunition and alternative non-lead ammunition results in the entry of copper and zinc into the edible parts of the game. Using non-lead ammunition does not entail dangerously elevated levels of copper and zinc, so replacing lead ammunition with alternative ammunition does not introduce a further health problem with regard to these metals. The levels of copper and zinc in game meat found in this study are in the range found in previous studies of game. The content of copper and zinc in game meat is also comparable to those regularly detected in meat and its products from livestock (pig, cattle, sheep) for which the mean human consumption rate is much higher. From the viewpoint of consumer health protection, the use of non-lead ammunition does not pose an additional hazard through copper and zinc contamination. A health risk due to the presence of copper and zinc in game meat at typical levels of consumer exposure is unlikely for both types of ammunition.

Low levels of copper reduce the reproductive success of a mobile invertebrate predator.

PubMed

Lee, Ka-Man; Johnston, Emma L

2007-09-01

Marine organisms that occur in urbanised bays can be exposed to low-level chronic pollution that results in sublethal changes to behavior or reproduction. The effects of low levels of copper on the reproductive success of a mobile invertebrate were assessed. Free living flatworms are common predators of bivalves and barnacles. Flatworms (Stylochus pygmaeus) were exposed to low levels of copper ranging from 0 to 25 microg L(-1) in the presence and absence of their barnacle prey (Balanus variegatus). Flatworms laid fewer egg batches when exposed to copper and the hatching success of the eggs was also reduced. Exposure to 25 microg L(-1) copper for 10 d reduced the reproductive success of flatworms by up to 80%. Results were consistent regardless of the presence or absence of prey (barnacles). Barnacles were only moderately affected by copper but exhibited major avoidance behavior (feeding inhibition) in the presence of flatworm predators. This is the first ecotoxicological study on marine flatworms. Experiments are required to quantify the effects of flatworm predator populations on sessile invertebrate community structure in the field.

Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes

PubMed Central

Gordon, Lily D.; Fang, Zhong; Holder, Robert C.; Reid, Sean D.

2015-01-01

ABSTRACT Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. IMPORTANCE Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. PMID:26013489

Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes.

PubMed

Young, Christie A; Gordon, Lily D; Fang, Zhong; Holder, Robert C; Reid, Sean D

2015-08-01

Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cytoplasmic CopZ-Like Protein and Periplasmic Rusticyanin and AcoP Proteins as Possible Copper Resistance Determinants in Acidithiobacillus ferrooxidans ATCC 23270.

PubMed

Navarro, Claudio A; von Bernath, Diego; Martínez-Bussenius, Cristóbal; Castillo, Rodrigo A; Jerez, Carlos A

2016-02-15

Acidophilic organisms, such as Acidithiobacillus ferrooxidans, possess high-level resistance to copper and other metals. A. ferrooxidans contains canonical copper resistance determinants present in other bacteria, such as CopA ATPases and RND efflux pumps, but these components do not entirely explain its high metal tolerance. The aim of this study was to find other possible copper resistance determinants in this bacterium. Transcriptional expression of A. ferrooxidans genes coding for a cytoplasmic CopZ-like copper-binding chaperone and the periplasmic copper-binding proteins rusticyanin and AcoP, which form part of an iron-oxidizing supercomplex, was found to increase when the microorganism was grown in the presence of copper. All of these proteins conferred more resistance to copper when expressed heterologously in a copper-sensitive Escherichia coli strain. This effect was absent when site-directed-mutation mutants of these proteins with altered copper-binding sites were used in this metal sensitivity assay. These results strongly suggest that the three copper-binding proteins analyzed here are copper resistance determinants in this extremophile and contribute to the high-level metal resistance of this industrially important biomining bacterium. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The influence of regional geological settings on the seismic hazard level in copper mines in the Legnica-Głogów Copper Belt Area (Poland)

NASA Astrophysics Data System (ADS)

Burtan, Zbigniew

2017-11-01

The current level of rockburst hazard in copper mines of the (LGOM) Legnica- Głogów Copper Belt Area is mostly the consequence of mining-induced seismicity, whilst the majority of rockbursting events registered to date were caused by high-energy tremors. The analysis of seismic readings in recent years reveals that the highest seismic activity among the copper mines in the LGOM is registered in the mine Rudna. This study investigates the seismic activity in the rock strata in the Rudna mine fields over the years 2006-2015. Of particular interest are the key seismicity parameters: the number of registered seismic events, the total energy emissions, the energy index. It appears that varied seismic activity in the area may be the function of several variables: effective mining thickness, the thickness of burst-prone strata and tectonic intensity. The results support and corroborate the view that principal factors influencing the actual seismic hazard level are regional geological conditions in the copper mines within the Legnica-Głogów Copper Belt Area.

High-speed off-axis holographic cinematography with a copper-vapor-pumped dye laser.

PubMed

Lauterborn, W; Judt, A; Schmitz, E

1993-01-01

A series of coherent light pulses is generated by pumping a dye laser with the pulsed output of a copper-vapor laser at rates of as much as 20 kHz. Holograms are recorded at this pulse rate on a rotating holographic plate. This technique of high-speed holographic cinematography is demonstrated by viewing the bubble filaments that appear in water under the action of a sound field of high intensity.

Influence of Dietary Copper on Serum Growth-Related Hormone Levels and Growth Performance of Weanling Pigs.

PubMed

Wang, Jianguo; Zhu, Xiaoyan; Guo, Yazhou; Wang, Zhe; Zhao, Baoyu; Yin, Yunhou; Liu, Guowen

2016-07-01

To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300 mg/kg copper sulfate for 80 days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20 days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300 mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250 mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P < 0.01), and the levels of GH, INS, IGF-1, and IGFBP-3 in serum were elevated significantly from the 20th to the 40th day of the experiment (P < 0.01). It is concluded that effects of copper supplemented in the diet on the growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs.

Effects of dietary supplementation with vitamin C and vitamin E and their combination on growth performance, some biochemical parameters, and oxidative stress induced by copper toxicity in broilers.

PubMed

Cinar, Miyase; Yildirim, Ebru; Yigit, A Arzu; Yalcinkaya, Ilkay; Duru, Ozkan; Kisa, Uçler; Atmaca, Nurgul

2014-05-01

This study investigated effects of dietary supplementation with vitamin C, vitamin E on performance, biochemical parameters, and oxidative stress induced by copper toxicity in broilers. A total of 240, 1-day-old, broilers were assigned to eight groups with three replicates of 10 chicks each. The groups were fed on the following diets: control (basal diet), vitamin C (250 mg/kg diet), vitamin E (250 mg/kg diet), vitamin C + vitamin E (250 mg/kg + 250 mg/kg diet), and copper (300 mg/kg diet) alone or in combination with the corresponding vitamins. At the 6th week, the body weights of broilers were decreased in copper, copper + vitamin E, and copper + vitamin C + vitamin E groups compared to control. The feed conversion ratio was poor in copper group. Plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase activities, iron, copper concentrations, and erythrocyte malondialdehyde were increased; plasma vitamin A and C concentrations and erythrocyte superoxide dismutase were decreased in copper group compared to control. Glutathione peroxidase, vitamin C, and iron levels were increased; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and copper levels were decreased in copper + vitamin C group, while superoxide dismutase, glutathione peroxidase, and vitamin E concentrations were increased; aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were decreased in copper with vitamin E group compared to copper group. The vitamin C concentrations were increased; copper, uric acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and malondialdehyde were decreased in copper + vitamin C + vitamin E group compared to copper group. To conclude, copper caused oxidative stress in broilers. The combination of vitamin C and vitamin E addition might alleviate the harmful effects of copper as demonstrated by decreased lipid peroxidation and hepatic enzymes.

Aberrant expression of copper associated genes after copper accumulation in COMMD1-deficient dogs.

PubMed

Favier, Robert P; Spee, Bart; Fieten, Hille; van den Ingh, Ted S G A M; Schotanus, Baukje A; Brinkhof, Bas; Rothuizen, Jan; Penning, Louis C

2015-01-01

COMMD1-deficient dogs progressively develop copper-induced chronic hepatitis. Since high copper leads to oxidative damage, we measured copper metabolism and oxidative stress related gene products during development of the disease. Five COMMD1-deficient dogs were studied from 6 months of age over a period of five years. Every 6 months blood was analysed and liver biopsies were taken for routine histological evaluation (grading of hepatitis), rubeanic acid copper staining and quantitative copper analysis. Expression of genes involved in copper metabolism (COX17, CCS, ATOX1, MT1A, CP, ATP7A, ATP7B, ) and oxidative stress (SOD1, catalase, GPX1 ) was measured by qPCR. Due to a sudden death of two animals, the remaining three dogs were treated with d-penicillamine from 43 months of age till the end of the study. Presented data for time points 48, 54, and 60 months was descriptive only. A progressive trend from slight to marked hepatitis was observed at histology, which was clearly preceded by an increase in semi-quantitative copper levels starting at 12 months until 42 months of age. During the progression of hepatitis most gene products measured were transiently increased. Most prominent was the rapid increase in the copper binding gene product MT1A mRNA levels. This was followed by a transient increase in ATP7A and ATP7B mRNA levels. In the sequence of events, copper accumulation induced progressive hepatitis followed by a transient increase in gene products associated with intracellular copper trafficking and temporal activation of anti-oxidative stress mechanisms. Copyright © 2014 Elsevier GmbH. All rights reserved.

In utero copper treatment for Menkes disease associated with a severe ATP7A mutation

PubMed Central

Haddad, Marie Reine; Macri, Charles J.; Holmes, Courtney S.; Goldstein, David S.; Jacobson, Beryl E.; Centeno, Jose A.; Popek, Edwina J.; Gahl, Willam A.; Kaler, Stephen G.

2012-01-01

Menkes disease is a lethal X-linked recessive neurodegenerative disorder of copper transport caused by mutations in ATP7A, which encodes a copper-transporting ATPase. Early postnatal treatment with copper injections often improves clinical outcomes in affected infants. While Menkes disease newborns appear normal neurologically, analyses of fetal tissues including placenta indicate abnormal copper distribution and suggest a prenatal onset of the metal transport defect. In an affected fetus whose parents found termination unacceptable and who understood the associated risks, we began in utero copper histidine treatment at 31.5 weeks gestational age. Copper histidine (900 μg per dose) was administered directly to the fetus by intramuscular injection (fetal quadriceps or gluteus) under ultrasound guidance. Percutaneous umbilical blood sampling enabled serial measurement of fetal copper and ceruloplasmin levels that were used to guide therapy over a four-week period. Fetal copper levels rose from 17 μg/dL prior to treatment to 45 μg/dL, and ceruloplasmin levels from 39 mg/L to 122 mg/L. After pulmonary maturity was confirmed biochemically, the baby was delivered at 35.5 weeks and daily copper histidine therapy (250 μg sc b.i.d.) was begun. Despite this very early intervention with copper, the infant showed hypotonia, developmental delay, and electroencephalographic abnormalities and died of respiratory failure at 5.5 months of age. The patient’s ATP7A mutation, which severely disrupted mRNA splicing, resulted in complete absence of ATP7A protein on Western blots. These investigations suggest that prenatally initiated copper replacement is inadequate to correct Menkes disease caused by severe loss-of-function mutations, and that postnatal ATP7A gene addition represents a rational approach in such circumstances. PMID:22695177

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gough, Mallory, E-mail: m.gough1@lancaster.ac.uk; Blanthorn-Hazell, Sophee, E-mail: s.blanthorn-hazell@lancaster.ac.uk; Delury, Craig, E-mail: c.delury@lancaster.ac.uk

Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enablemore » cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.« less

Talitrid amphipods (Crustacea) as biomonitors for copper and zinc

NASA Astrophysics Data System (ADS)

Rainbow, P. S.; Moore, P. G.; Watson, D.

1989-06-01

Data are presented on the copper and zinc concentrations of four talitrid amphipod species (standard dry weight 10 mg), i.e. Orchestia gammarellus (Pallas), O. mediterranea Costa, Talitrus saltator Montagu and Talorchestia deshayesii (Audouin), from 31 sites in S.W. Scotland, N. Wales and S.W. England. More limited data are also presented for cadmium in O. gammarellus (three sites) and T. deshayesii (one site). In S.W. Scotland, copper concentrations were raised significantly in O. gammarellus from Whithorn and Auchencairn (Solway) and Loch Long and Holy Loch (Clyde). In S.W. England, copper concentrations were highest at Restronguet Creek, Torpoint and Gannel (Cornwall). Samples of O. gammarellus from Islay (inner Hebrides) taken adjacent to the effluent outfalls of local whisky distilleries fell into two groups based on copper concentrations (presumably derived from copper stills), the higher copper levels deriving from the more productive distilleries. High copper levels were found in T. saltator and Tal. deshayesii from Dulas Bay (Wales). Zinc levels in O. gammarellus were high in Holy Loch and Auchencairn (Scotland), Gannel and Torpoint (England) but extremely elevated (as was Zn in O. mediterranea) at Restronguet Creek. Zinc was also high in T. saltator from Dulas Bay (Wales), but not in Tal. deshayesii. Cadmium levels in O. gammarellus from Kilve (Bristol Channel) were much raised. These differences (a) conform with expectations of elevated bioavailability of these metals from well researched areas (S.W. England & N. Wales), and (b) identify hitherto unappreciated areas of enrichment in S.W. Scotland. Orchestia gammarellus is put forward as a suitable biomonitor for copper and zinc in British coastal waters.

Wilson disease - currently used anticopper therapy.

PubMed

Członkowska, Anna; Litwin, Tomasz

2017-01-01

Wilson disease (WD) is a genetic disorder of copper metabolism that can be treated successfully with pharmacologic treatment. Two groups of drugs are currently used: chelators (e.g., d-penicillamine and trientine), which increase urinary copper excretion, and zinc salts, which inhibit copper absorption in the digestive tract. The mechanisms of action lead to a negative copper balance, stopping pathologic accumulation of copper in the tissues and clearing affected organs of copper overload. Due to a lack of prospective clinical trials, the use of drugs depends mainly on center experience and the accessibility in different countries or regions. This chapter presents the different reports and recommendations regarding WD treatment. In addition to the different expert opinions on pharmacologic agents, there are a few axioms regarding WD treatment: treatment should start immediately after diagnosis, even in clinically presymptomatic cases; the patient should be treated for life, making compliance a key factor in treatment success; and the treatment should be monitored regularly via liver and hematologic tests, neurologic examination, and copper metabolism, modifying the treatment accordingly. Other drugs proposed for WD treatment (e.g., tetrathiomolybdate) are in clinical trials and lack current recommendations. Thus, only the currently available options for WD pharmacologic treatment are discussed. © 2017 Elsevier B.V. All rights reserved.

Plant polyphenols mobilize nuclear copper in human peripheral lymphocytes leading to oxidatively generated DNA breakage: implications for an anticancer mechanism.

PubMed

Shamim, Uzma; Hanif, Sarmad; Ullah, M F; Azmi, Asfar S; Bhat, Showket H; Hadi, S M

2008-08-01

It was earlier proposed that an important anti-cancer mechanism of plant polyphenols may involve mobilization of endogenous copper ions, possibly chromatin-bound copper and the consequent pro-oxidant action. This paper shows that plant polyphenols are able to mobilize nuclear copper in human lymphocytes, leading to degradation of cellular DNA. A cellular system of lymphocytes isolated from human peripheral blood and comet assay was used for this purpose. Incubation of lymphocytes with neocuproine (a cell membrane permeable copper chelator) inhibited DNA degradation in intact lymphocytes. Bathocuproine, which is unable to permeate through the cell membrane, did not cause such inhibition. This study has further shown that polyphenols are able to degrade DNA in cell nuclei and that such DNA degradation is inhibited by neocuproine as well as bathocuproine (both of which are able to permeate the nuclear pore complex), suggesting that nuclear copper is mobilized in this reaction. Pre-incubation of lymphocyte nuclei with polyphenols indicates that it is capable of traversing the nuclear membrane. This study has also shown that polyphenols generate oxidative stress in lymphocyte nuclei which is inhibited by scavengers of reactive oxygen species (ROS) and neocuproine. These results indicate that the generation of ROS occurs through mobilization of nuclear copper resulting in oxidatively generated DNA breakage.

LONG-TERM IMPACTS OF ORTHOPHOSPHATE TREATMENT ON COPPER LEVELS - PRESENTATION

EPA Science Inventory

Laboratory, pilot, and field data collected support the theoretical "cupric hydroxide" copper solubility model. For the short time frames inherent in laboratory and pilot studies of copper solubility and in initial field monitoring for the LCR from Tier 1 soldered copper sites, c...

LONG-TERM IMPACTS OF ORTHOPHOSPHATE TREATMENT ON COPPER LEVELS

EPA Science Inventory

Laboratory, pilot, and field data collected support the theoretical “cupric hydroxide” copper solubility model. For the short time frames inherent in laboratory and pilot studies of copper solubility and in initial field monitoring for the LCR from Tier 1 soldered copper sites,...

Dietary copper in excess of nutritional requirement reduces plasma and breast muscle cholesterol of chickens.

PubMed

Bakalli, R I; Pesti, G M; Ragland, W L; Konjufca, V

1995-02-01

Male commercial broiler strain chickens were fed from hatching to 42 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 250 mg copper/kg diet from cupric sulfate pentahydrate (for 35 or 42 d). Hypocholesterolemia (11.8% reduction) and decreased breast muscle cholesterol (20.4% reduction) were observed in copper-supplemented birds. There was a slight increase (P > .05) in breast muscle copper (14.5%), and all levels were very low (< .5 mg/kg). Feeding copper for 42 vs 35 d resulted in lower levels of cholesterol in the plasma (12.9 vs 10.8% reduction) and breast muscle (24.6 vs 16.2% reduction). Very similar results were found in two additional experiments in which hypocholesterolemia and reduced breast muscle cholesterol were associated with reduced plasma triglycerides and blood reduced glutathione. It is well known that hypercholesterolemia is a symptom of dietary copper deficiency. The data presented here indicate that blood and breast muscle cholesterol are inversely related to dietary copper in excess of the dietary requirement for maximal growth. The cholesterol content of the edible muscle tissue of broiler chickens can be reduced by approximately 25% after feeding a supranormal level of copper for 42 d without altering the growth of the chickens or substantially increasing the copper content of the edible meat.

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation.

PubMed

Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

2015-12-01

Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

PubMed Central

Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

2016-01-01

Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies. PMID:26587712

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

NASA Astrophysics Data System (ADS)

Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

2015-12-01

Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

Present knowledge and perspectives on the role of copper in brake materials and related environmental issues: A critical assessment.

PubMed

Straffelini, Giovanni; Ciudin, Rodica; Ciotti, Alessandro; Gialanella, Stefano

2015-12-01

This critical review presents several aspects related to the use of copper as a main component in brake pads in road vehicles. The compositions of these materials are attracting increasing interest and concern due to the relative contribution of wear products to particulate matter emissions in the environment as a result of braking action even though there has been a reduction in exhaust products from internal combustion engines. We review the data on the main wear mechanisms in brake systems and highlight the positive role of copper. However, similar to other heavy metal emissions, even the release of copper into the atmosphere may have important environmental and health effects. Thus, several replacement strategies are being pursued, and the positive and negative features will be critically reviewed. Additionally, the future perspectives in materials development will be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Arsenic exposure levels in relation to different working departments in a copper mining and smelting plant

NASA Astrophysics Data System (ADS)

Sun, Qingshan; Song, Yingli; Liu, Shengnan; Wang, Fei; Zhang, Lin; Xi, Shuhua; Sun, Guifan

2015-10-01

The investigation was carried out to evaluate arsenic exposure and the urine metabolite profiles of workers with different working departments, including administration (Group1), copper ore mining (Group2), copper ore grinding (Group3), electrolytic procession (Group4) and copper smelting (Group5) in a Copper mining and processing plant in China. Information about characteristics of each subject was obtained by questionnaire and inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine were determined. The highest urinary levels of iAs, MMA and DMA all were found in the Group 5. Group 4 workers had a higher iAs% and a lower PMI compared to Group 3. The urinary total As (TAs) levels of 54.7% subjects exceeded 50 μg/g Cr, and the highest percentage (93.3%) was found in Group 5, smelters. The results of the present study indicate that workers in copper production plant indeed exposed to As, especially for smelters and workers of electrolytic process.

Mitochondrial Copper Metabolism and Delivery to Cytochrome c Oxidase

PubMed Central

Horn, Darryl; Barrientos, Antoni

2010-01-01

Summary Metals are essential elements of all living organisms. Among them, copper is required for a multiplicity of functions including mitochondrial oxidative phosphorylation and protection against oxidative stress. Here we will focus on describing the pathways involved in the delivery of copper to cytochrome c oxidase (COX), a mitochondrial metalloenzyme acting as the terminal enzyme of the mitochondrial respiratory chain. The catalytic core of COX is formed by three mitochondrially-encoded subunits and contains three copper atoms. Two copper atoms bound to subunit 2 constitute the CuA site, the primary acceptor of electrons from ferrocytochrome c. The third copper, CuB, is associated with the high-spin heme a3 group of subunit 1. Recent studies, mostly performed in the yeast Saccharomyces cerevisiae, have provided new clues about 1- the source of the copper used for COX metallation; 2- the roles of Sco1p and Cox11p, the proteins involved in the direct delivery of copper to the CuA and CuB sites, respectively; 3- the action mechanism of Cox17p, a copper chaperone that provides copper to Sco1p and Cox11p; 4- the existence of at least four Cox17p homologues carrying a similar twin CX9C domain suggestive of metal binding, Cox19p, Cox23p, Pet191p and Cmc1p, that could be part of the same pathway; and 5- the presence of a disulfide relay system in the intermembrane space of mitochondria that mediates import of proteins with conserved cysteines motifs such as the CX9C characteristic of Cox17p and its homologues. The different pathways are reviewed and discussed in the context of both mitochondrial COX assembly and copper homeostasis. PMID:18459161

Effects of Dietary Copper and Zinc Supplementation on Growth Performance, Tissue Mineral Retention, Antioxidant Status, and Fur Quality in Growing-Furring Blue Foxes (Alopex lagopus).

PubMed

Liu, Zhi; Wu, Xuezhuang; Zhang, Tietao; Guo, Jungang; Gao, Xiuhua; Yang, Fuhe; Xing, Xiumei

2015-12-01

A 4×2 factorial experiment with four supplemental levels of copper (0, 20, 40, or 60 mg copper per kg dry matter) from copper sulfate and two supplemental levels of zinc (40 or 200 mg zinc per kg dry matter) from zinc sulfate was conducted to investigate the effects of dietary copper and zinc supplementation on growth performance, tissue mineral retention, antioxidant status, and fur quality in growing-furring blue foxes. One hundred and twenty healthy 15-week-old male blue foxes were randomly allocated to eight dietary treatments with 15 replicates per treatment for a 70-day trial from mid-September to pelting in December. The average daily gain and feed conversion ratio were increased with copper supplementation in the first 35 days as well as the overall period (P<0.05). In addition, copper supplementation tended to increase feed intake during the first 35 days (P<0.10). Diets supplemented with 200 mg/kg zinc did not affect body gain (P>0.10) and feed intake (P>0.10) but improved feed conversion (P<0.05) compared with those supplemented 40 mg/kg zinc throughout the experiment. No copper×zinc interaction was observed for growth performance except that a tendency (P=0.09) was found for feed intake in the first 35 days. Supplementation of copper or zinc improved crude fat digestibility (P<0.01) but had no effects on the digestibility of other nutrients. Fecal copper was increased with both copper (P<0.01) and zinc addition (P<0.05). However, fecal zinc was affected only by dietary zinc addition (P<0.01). Mineral contents in serum and kidney were not affected by dietary treatments (P>0.05). However, the level of copper in the liver was increased with copper supplementation (P<0.05) and tended to decrease with zinc supplementation (P=0.08). Dietary zinc addition tended to increase the activity of alkaline phosphatase (P=0.07). The activities of copper-zinc superoxide dismutase and catalase tended to increase by copper (P=0.08) and zinc addition (P=0.05). Moreover, a copper×zinc interaction was observed for catalase in the experiment (P<0.05). Serum malondialdehyde concentration decreased with the increasing of dietary copper and zinc levels (P<0.05). The activity of glutathione peroxidase tended to increase by copper addition (P=0.09). For fur quality, foxes fed diets supplemented with high copper had larger skin length and darker pelts than those fed the basal diet without copper addition (P<0.05). In conclusion, this study demonstrated that dietary copper and zinc supplementation can improve growth by increasing feed intake and improving fat digestibility. Additionally, copper and zinc can enhance the antioxidant capacity of blue foxes. This study also indicates that additional zinc up to 200 mg/kg did not exert significant adverse effects on the copper metabolism of growing-furring blue foxes.

Rapid Copper Acquisition by Developing Murine Mesothelioma: Decreasing Bioavailable Copper Slows Tumor Growth, Normalizes Vessels and Promotes T Cell Infiltration

PubMed Central

Crowe, Andrew; Jackaman, Connie; Beddoes, Katie M.; Ricciardo, Belinda; Nelson, Delia J.

2013-01-01

Copper, an essential trace element acquired through nutrition, is an important co-factor for pro-angiogenic factors including vascular endothelial growth factor (VEGF). Decreasing bioavailable copper has been used as an anti-angiogenic and anti-cancer strategy with promising results. However, the role of copper and its potential as a therapy in mesothelioma is not yet well understood. Therefore, we monitored copper levels in progressing murine mesothelioma tumors and analyzed the effects of lowering bioavailable copper. Copper levels in tumors and organs were assayed using atomic absorption spectrophotometry. Mesothelioma tumors rapidly sequestered copper at early stages of development, the copper was then dispersed throughout growing tumor tissues. These data imply that copper uptake may play an important role in early tumor development. Lowering bioavailable copper using the copper chelators, penicillamine, trientine or tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody therapy. The impact of copper lowering on tumor blood vessels and tumor infiltrating T cells was measured using flow cytometry and confocal microscopy. Copper lowering was associated with reduced tumor vessel diameter, reduced endothelial cell proliferation (reduced Ki67 expression) and lower surface ICAM/CD54 expression implying reduced endothelial cell activation, in a process similar to endothelial normalization. Copper lowering was also associated with a CD4+ T cell infiltrate. In conclusion, these data suggest copper lowering is a potentially useful anti-mesothelioma treatment strategy that slows tumor growth to provide a window of opportunity for inclusion of other treatment modalities to improve patient outcomes. PMID:24013775

ATP7B mediates vesicular sequestration of copper: insight into biliary copper excretion.

PubMed

Cater, Michael A; La Fontaine, Sharon; Shield, Kristy; Deal, Yolanda; Mercer, Julian F B

2006-02-01

The Wilson protein (ATP7B) regulates levels of systemic copper by excreting excess copper into bile. It is not clear whether ATP7B translocates excess intrahepatic copper directly across the canalicular membrane or sequesters this copper into exocytic vesicles, which subsequently fuse with canalicular membrane to expel their contents into bile. The aim of this study was to clarify the mechanism underlying ATP7B-mediated copper detoxification by investigating endogenous ATP7B localization in the HepG2 hepatoma cell line and its ability to mediate vesicular sequestration of excess intracellular copper. Immunofluorescence microscopy was used to investigate the effect of copper concentration on the localization of endogenous ATP7B in HepG2 cells. Copper accumulation studies to determine whether ATP7B can mediate vesicular sequestration of excess intracellular copper were performed using Chinese hamster ovary cells that exogenously expressed wild-type and mutant ATP7B proteins. In HepG2 cells, elevated copper levels stimulated trafficking of ATP7B to pericanalicular vesicles and not to the canalicular membrane as previously reported. Mutation of an endocytic retrieval signal in ATP7B caused the protein to constitutively localize to vesicles and not to the plasma membrane, suggesting that a vesicular compartment(s) is the final trafficking destination for ATP7B. Expression of wild-type and mutant ATP7B caused Chinese hamster ovary cells to accumulate copper in vesicles, which subsequently undergo exocytosis, releasing copper across the plasma membrane. This report provides compelling evidence that the primary mechanism of biliary copper excretion involves ATP7B-mediated vesicular sequestration of copper rather than direct copper translocation across the canalicular membrane.

Substance flow analysis as a tool for urban water management.

PubMed

Chèvre, N; Guignard, C; Rossi, L; Pfeifer, H-R; Bader, H-P; Scheidegger, R

2011-01-01

Human activity results in the production of a wide range of pollutants that can enter the water cycle through stormwater or wastewater. Among others, heavy metals are still detected in high concentrations around urban areas and their impact on aquatic organisms is of major concern. In this study, we propose to use a substance flow analysis as a tool for heavy metals management in urban areas. We illustrate the approach with the case of copper in Lausanne, Switzerland. The results show that around 1,500 kg of copper enter the aquatic compartment yearly. This amount contributes to sediment enrichment, which may pose a long-term risk for benthic organisms. The major sources of copper in receiving surface water are roofs and catenaries of trolleybuses. They represent 75% of the total input of copper into the urban water system. Actions to reduce copper pollution should therefore focus on these sources. Substance flow analysis also highlights that copper enters surface water mainly during rain events, i.e., without passing through any treatment procedure. A reduction in pollution could also be achieved by improving stormwater management. In conclusion, the study showed that substance flow analysis is a very effective tool for sustainable urban water management.

The Role of Trace Elements in Tinnitus.

PubMed

Yaşar, Mehmet; Şahin, Mehmet İlhan; Karakükçü, Çiğdem; Güneri, Erhan; Doğan, Murat; Sağıt, Mustafa

2017-03-01

In this study, we aimed to investigate the role of three trace elements, namely, zinc, copper, and lead, in tinnitus by analyzing the serum level of copper and lead and both the serum and tissue level of zinc. Eighty patients, who applied to outpatient otolaryngology clinic with the complaints of having tinnitus, and 28 healthy volunteers were included. High-frequency audiometry was performed, and participants who had hearing loss according to the pure tone average were excluded; tinnitus frequency and loudness were determined and tinnitus reaction questionnaire scores were obtained from the patients. Of all the participants, serum zinc, copper, and lead values were measured; moreover, zinc levels were examined in hair samples. The levels of trace elements were compared between tinnitus and control groups. The level of copper was found to be significantly lower in the tinnitus group (p = 0.02), but there was no significant difference between the groups in terms of the levels of zinc, neither in serum nor in hair, and lead in serum (p > 0.05). The lack of trace elements, especially that of "zinc," have been doubted for the etiopathogenesis of tinnitus in the literature; however, we only found copper levels to be low in patients having tinnitus.

Evaluation of Serum Levels of Zinc, Copper, Iron, and Zinc/Copper Ratio in Cutaneous Leishmaniasis

PubMed Central

Pourfallah, F; Javadian, S; Zamani, Z; Saghiri, R; Sadeghi, S; Zarea, B; Faiaz, Sh; Mirkhani, F; Fatemi, N

2009-01-01

Background: The purpose of this study was to evaluate the levels of zinc (Zn), copper (Cu), iron (Fe) and zinc/ copper ratio in the serum of patients with cutaneous leishmaniasis in Qom Province, center of Iran. Methods: Serum levels of zinc and copper were determined by flame atomic absorption spectrophotometer and serum iron concentration was measured by using an Auto Analyzer. The study group consisted of 60 patients with cutaneous leishmaniasis and the control group of 100 healthy volunteers from the same area who were not exposed to cutaneous leishmaniasis. Result: There were no statistically significant differences in age and body mass index between the two groups. Serum Zn (P< 0.001) and Fe (P< 0.05) levels were lower in patients with cutaneous leishmaniasis than the control group. We also found serum Cu concentration (P< 0.05) in the patient group was significantly higher than that of the control group. However, zinc/ copper ratio (P< 0.001) was lower in patients with cutaneous leishmaniasis than in the control group. Conclusion: Our data indicated that Zn/Cu ratio was significantly lower in patients with CL as compared to the controls. Earlier reports suggest that, this ratio imbalance could be a useful marker for immune dysfunction in leishmaniasis. There was also strong association of Zn, Cu and Fe with CL. It suggests the use of blood zinc, copper, iron concentration and the copper/zinc ratio (Zn/Cu), as a means for estimating the prognosis of CL. PMID:22808376

Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake

PubMed Central

Ranganathan, Perungavur N.; Lu, Yan; Jiang, Lingli; Kim, Changae

2011-01-01

Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency. PMID:21768302

In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease

PubMed Central

Heffern, Marie C.; Park, Hyo Min; Au-Yeung, Ho Yu; Van de Bittner, Genevieve C.; Ackerman, Cheri M.; Stahl, Andreas; Chang, Christopher J.

2016-01-01

Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex interplay between copper status, health, and disease in the same living organism over time. Here, we present the synthesis, characterization, and in vivo imaging applications of Copper-Caged Luciferin-1 (CCL-1), a bioluminescent reporter for tissue-specific copper visualization in living animals. CCL-1 uses a selective copper(I)-dependent oxidative cleavage reaction to release d-luciferin for subsequent bioluminescent reaction with firefly luciferase. The probe can detect physiological changes in labile Cu+ levels in live cells and mice under situations of copper deficiency or overload. Application of CCL-1 to mice with liver-specific luciferase expression in a diet-induced model of nonalcoholic fatty liver disease reveals onset of hepatic copper deficiency and altered expression levels of central copper trafficking proteins that accompany symptoms of glucose intolerance and weight gain. The data connect copper dysregulation to metabolic liver disease and provide a starting point for expanding the toolbox of reactivity-based chemical reporters for cell- and tissue-specific in vivo imaging. PMID:27911810

The Effect of Helicobacter pylori Eradication on the Levels of Essential Trace Elements

PubMed Central

Wu, Meng-Chieh; Huang, Chun-Yi; Kuo, Fu-Chen; Hsu, Wen-Hung; Wang, Sophie S. W.; Shih, Hsiang-Yao; Liu, Chung-Jung; Chen, Yen-Hsu; Wu, Deng-Chyang; Huang, Yeou-Lih; Lu, Chien-Yu

2014-01-01

Objective. This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. Patients and Methods. We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. Results. Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P = 0.06). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P < 0.05). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. Conclusion. H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327). PMID:25548772

Heavy metal pollution among autoworkers. II. Cadmium, chromium, copper, manganese, and nickel.

PubMed Central

Clausen, J; Rastogi, S C

1977-01-01

Garages and auto-repair workshops may be polluted with other heavy metals besides lead. Blood of autoworkers with high lead content was analysed for cadmium, chromium, copper manganese, nickel, ALAD activity and carboxyhaemoglobin level. Cadmium and copper levels in blood of autoworkers were comparable with those of the control subjects while chroimium and nickel levels were significantly higher (P less than 0-01 for both metals), and scattered raised values of manganese were found. There was no significant mutual correlation between levels of various heavy metals determined in whole blood. High copper levels were slightly related to decreasing ALAD activity (P less than 0-1). Nineteen per cent of autoworkers were found to have an abnormally blood level of carboxyhaemoglobin. The amount of particulate heavy metal in autoworkshop air was not related to biochemical abnormalities found in the autoworkers. Various sources of pollution of these heavy metals in autoworkshops are discussed. PMID:71915

Facilities Engineering Applications Program: Lead Monitoring Strategies for Drinking Water Systems: Lessons Learned

DTIC Science & Technology

1991-02-01

significant amount of lead mobilization. Studies by Lyson and Lenihan,ŝ Wong and Berrang,2 ° and Ierrra, t al.2’ describe this action and document the...Karaleka,. Jr. 1m I) V. Dc err , c a). T. Lyson and J. Lcnihan. ’Corrosion in Solder Jointed Copper tbes Resulting in Lead Contamination of Drinking...Boston Area," Journal of the New England Water Works Association, Vol 90 (1976). Lyson , T., and J. Lenihan, "Corrosion in Solder Jointed Copper Tubes

Gene expression patterns in the progression of canine copper-associated chronic hepatitis

PubMed Central

Dirksen, Karen; Spee, Bart; Penning, Louis C.; van den Ingh, Ted S. G. A. M.; Burgener, Iwan A.; Watson, Adrian L.; Groot Koerkamp, Marian; Rothuizen, Jan

2017-01-01

Copper is an essential trace element, but can become toxic when present in abundance. The severe effects of copper-metabolism imbalance are illustrated by the inherited disorders Wilson disease and Menkes disease. The Labrador retriever dog breed is a novel non-rodent model for copper-storage disorders carrying mutations in genes known to be involved in copper transport. Besides disease initiation and progression of copper accumulation, the molecular mechanisms and pathways involved in progression towards copper-associated chronic hepatitis still remain unclear. Using expression levels of targeted candidate genes as well as transcriptome micro-arrays in liver tissue of Labrador retrievers in different stages of copper-associated hepatitis, pathways involved in progression of the disease were studied. At the initial phase of increased hepatic copper levels, transcriptomic alterations in livers mainly revealed enrichment for cell adhesion, developmental, inflammatory, and cytoskeleton pathways. Upregulation of targeted MT1A and COMMD1 mRNA shows the liver’s first response to rising intrahepatic copper concentrations. In livers with copper-associated hepatitis mainly an activation of inflammatory pathways is detected. Once the hepatitis is in the chronic stage, transcriptional differences are found in cell adhesion adaptations and cytoskeleton remodelling. In view of the high similarities in copper-associated hepatopathies between men and dog extrapolation of these dog data into human biomedicine seems feasible. PMID:28459846

Copper and Lead Corrosion in a Full Scale Home Plumbning system Simulation

EPA Science Inventory

The corrosion of household or premise plumbing materials (such as copper, brass, and solder) and the metal release that results from that corrosion can cause numerous problems, ranging from elevated lead and copper levels to blue water and copper pinhole leaks. If left untreate...

Aquatic Life Criteria - Copper

EPA Pesticide Factsheets

Documents pertain to Aquatic Life Ambient Water Quality criteria for Copper (2007 Freshwater, 2016 Estuarine/marine). These documents contain the safe levels of Copper in water that should protect to the majority of species.

Acute gastrointestinal effects of graded levels of copper in drinking water.

PubMed Central

Pizarro, F; Olivares, M; Uauy, R; Contreras, P; Rebelo, A; Gidi, V

1999-01-01

The objective of this study was to determine the acute gastrointestinal effects caused by the consumption of drinking water containing graded levels of added copper. Sixty healthy, adult women were randomly assigned to receive copper [Cu(II)] at four concentrations in their drinking water following a Latin-square design. Each group (n = 15) received tap water with no added copper, 1, 3, and 5 mg Cu/l of added copper sulfate for a 2-week study period, followed by 1 week of standard tap water. The subjects recorded their water consumption and gastrointestinal symptoms daily on a special form. The average daily consumption of water was 1.64 liters per subject, regardless of the amount of copper added. Final serum copper, ceruloplasmin, and liver enzymes were measured in all subjects and were not different from baseline concentrations. Twenty-one subjects (35%) recorded gastrointestinal disturbances sometime during the study, 9 had diarrhea, some with abdominal pain and vomiting, and 12 subjects presented abdominal pain, nausea, or vomiting. There was no association between copper levels in drinking water and diarrhea. However, nausea, abdominal pain, or vomiting were significantly related to copper concentrations in water. The recorded incidence rate of these symptoms was 5, 2, 17, and 15% while ingesting water with 0, 1, 3, and 5 mg Cu/l, respectively (overall [chi]2 = 11.3, p<0.01; Cu [less than/equal to]1 mg/l versus Cu [Greater than/equal to]3 mg/l, [chi]2, p<0.01). When subjects interrupted their consumption of drinking water with added copper, most symptoms disappeared. We conclude that under the conditions of the study, there was no association between aggregate copper in drinking water within the range of 0-5 mg/l and diarrhea, but a [Greater than/equal to]3 mg Cu/l level of ionized copper was associated with nausea, abdominal pain, or vomiting. Additional studies with sufficient numbers of subjects are needed to define thresholds for specific gastrointestinal symptoms with precision and to extrapolate these results to the population at large. Images Figure 1 Figure 2 PMID:9924006

Occurrence of the Transferable Copper Resistance Gene tcrB among Fecal Enterococci of U.S. Feedlot Cattle Fed Copper-Supplemented Diets

PubMed Central

Amachawadi, R. G.; Alvarado, C. A.; Mainini, T. R.; Vinasco, J.; Drouillard, J. S.; Nagaraja, T. G.

2013-01-01

Copper, an essential micronutrient, is supplemented in the diet at elevated levels to reduce morbidity and mortality and to promote growth in feedlot cattle. Gut bacteria exposed to copper can acquire resistance, which among enterococci is conferred by a transferable copper resistance gene (tcrB) borne on a plasmid. The present study was undertaken to investigate whether the feeding of copper at levels sufficient to promote growth increases the prevalence of the tcrB gene among the fecal enterococci of feedlot cattle. The study was performed with 261 crossbred yearling heifers housed in 24 pens, with pens assigned randomly to a 2×2 factorial arrangement of treatments consisting of dietary copper and a commercial linseed meal-based energy protein supplement. A total of 22 isolates, each identified as Enterococcus faecium, were positive for tcrB with an overall prevalence of 3.8% (22/576). The prevalence was higher among the cattle fed diets supplemented with copper (6.9%) compared to normal copper levels (0.7%). The tcrB-positive isolates always contained both erm(B) and tet(M) genes. Median copper MICs for tcrB-positive and tcrB-negative enterococci were 22 and 4 mM, respectively. The transferability of the tcrB gene was demonstrated via a filter-mating assay. Multilocus variable number tandem repeat analysis revealed a genetically diverse population of enterococci. The finding of a strong association between the copper resistance gene and other antibiotic (tetracycline and tylosin) resistance determinants is significant because enterococci remain potential pathogens and have the propensity to transfer resistance genes to other bacteria in the gut. PMID:23666328

Copper-complexing ligands produced by an intact estuarine microbial community in response to copper stress.

NASA Astrophysics Data System (ADS)

Bingham, J.; Dryden, C.; Gordon, A.

2002-12-01

Copper is both an important nutrient and a pollutant in the marine environment. By studying the interactions between microorganisms and copper in the Elizabeth River (VA), home to a major Naval Base, we field tested the hypothesis that picoplankton and/or bacterioplankton produce strong, copper-complexing ligands in response to elevated copper concentrations. A simple light/ dark test was used to distinguish between heterotrophic and phototrophic ligand production. Samples were bottled and moored, submerged one meter, for a week. Direct counts using DAPI stain and epiflourescence were conducted to find concentrations of picoplankton and bacterioplankton. Using cathodic stripping voltammetry, we found the total copper concentrations, and then from a titration of the ligands by copper, the ligand concentrations and conditional stability constants were obtained. The Elizabeth River naturally had between 10-20 nM total dissolved copper concentrations. However when copper complexation was considered we found that the levels of bio-available Cu(II) ions were much lower. In fact in the natural samples the levels were not high enough to affect the relative reproductive rates of several microorganisms. Naturally there was a 50 nM "buffer zone" of ligand to total dissolved copper concentration. Furthermore, when stressed with excess copper, healthy picoplankton produced enough ligand to alleviate toxicity, and rebuild the buffer zone. However bacterioplankton only produced enough ligand so that they were no longer affected. Therefore, intact estuarine communities regulate copper bioavailability and toxicity with ligand production.

Copper ions stimulate the proliferation of hepatic stellate cells via oxygen stress in vitro.

PubMed

Xu, San-qing; Zhu, Hui-yun; Lin, Jian-guo; Su, Tang-feng; Liu, Yan; Luo, Xiao-ping

2013-02-01

This study examined the effect of copper ions on the proliferation of hepatic stellate cells (HSCs) and the role of oxidative stress in this process in order to gain insight into the mechanism of hepatic fibrosis in Wilson's disease. LX-2 cells, a cell line of human HSCs, were cultured in vitro and treated with different agents including copper sulfate, N-acetyl cysteine (NAC) and buthionine sulfoximine (BSO) for different time. The proliferation of LX-2 cells was measured by non-radioactive cell proliferation assay. Real-time PCR and Western blotting were used to detect the mRNA and protein expression of platelet-derived growth factor receptor β subunit (PDGFβR), ELISA to determine the level of glutathione (GSH) and oxidized glutathione (GSSG), dichlorofluorescein assay to measure the level of reactive oxygen species (ROS), and lipid hydroperoxide assay to quantify the level of lipid peroxide (LPO). The results showed that copper sulfate over a certain concentration range could promote the proliferation of LX-2 cells in a time- and dose-dependent manner. The effect was most manifest when LX-2 cells were treated with copper sulfate at a concentration of 100 μmol/L for 24 h. Additionally, copper sulfate could dose-dependently increase the levels of ROS and LPO, and decrease the ratio of GSH/GSSG in LX-2 cells. The copper-induced increase in mRNA and protein expression of PDGFβR was significantly inhibited in LX-2 cells pre-treated with NAC, a precursor of GSH, and this phenomenon could be reversed by the intervention of BSO, an inhibitor of NAC. It was concluded that copper ions may directly stimulate the proliferation of HSCs via oxidative stress. Anti-oxidative stress therapies may help suppress the copper-induced activation and proliferation of HSCs.

The influence of duckweed species diversity on ecophysiological tolerance to copper exposure.

PubMed

Zhao, Zhao; Shi, Huijuan; Duan, Dongzhu; Li, Hongmei; Lei, Tingwen; Wang, Maolin; Zhao, Hai; Zhao, Yun

2015-07-01

In excess, copper is toxic to plants. In the plants, Landoltia punctata and Lemna minor grown in mixed and monoculture, the effects of exposure to varying concentrations of copper (0.01, 0.1, 0.5 and 1mgL(-1) Cu) for seven days were assessed by measuring changes in the chlorophyll, protein and malondialdehyde (MDA) content, catalase (CAT), superoxide dismutase (SOD) and ascorbate peroxidase (APX) activity. According to results, Cu levels in plants increased with increasing Cu concentration. The level of photosynthetic pigments and crude proteins decreased only upon exposure to high Cu concentrations. However, the starch and malondialdehyde (MDA) content increased. These results suggested a stress alleviation that was possibly the result of antioxidants such as CAT and SOD, the activities of which increased with increasing Cu levels. APX activity increased in L. punctata, but decreased in L. minor, under monoculture or mixed culture conditions. In addition, the duckweed in mixed culture exhibited increased antioxidant enzyme activities which provide increased resistance to copper in moderate copper concentrations. As the copper concentration increased, the duckweed in the mixed culture limited the uptake of copper to avoid toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Urea increased nickel and copper accumulation in the leaves of Egeria densa (Planch.) Casp. and Ceratophyllum demersum L. during short-term exposure.

PubMed

Maleva, Maria; Borisova, Galina; Chukina, Nadezhda; Kumar, Adarsh

2018-02-01

In the present study, two fresh water plant species Egeria densa (Planch.) Casp. and Ceratophyllum demersum L. were subjected to separate and combined action of urea (2mМ) and metals (Ni and Cu, 10μM) to investigate the phytoremediation potential of these two submerged macrophytes during short-term experiments (48h). Both submerged macrophytes demonstrated high accumulative potential for Ni and Cu (average bioconcentration factors were 2505 for Ni and 3778 for Cu). The urea (2 mM) was not significantly toxic for studied plant species. Futhermore, urea worked as an additional source of nitrogen and stimulated some metabolic processes such as the synthesis of photosynthetic pigments, soluble proteins, non-enzymatic antioxidants, and activated some enzymes. Adding urea to the metals increased their accumulation in both macrophytes (on average by 35% for Ni and 15% for Cu). Combined action of urea and Ni did not have a significant effect on antioxidant response, but caused a sharp increase of urease activity (4 folds on an average) in both plants. The copper exerted a stronger toxic effect on both studied macrophytes compared to nickel. Adding urea to copper in some cases diminished the toxic action of this metal. Study concludes that the responses of E. densa and C. demersum to urea and metal action (separate and combined) were depended on the type of pollutant and the activity of antioxidant defence system. Therefore, the studied aquatic macrophytes found to be potential phytoremediators of water bodies, the addition of an organic nitrogen source in the form of urea in environmentally relevant concentration will increase the efficiency of phytoextraction of metals. Copyright © 2017 Elsevier Inc. All rights reserved.

Copper stress and filamentous fungus Humicola lutea 103 - ultrastructural changes and activities of key metabolic enzymes.

PubMed

Krumova, Ekaterina Ts; Stoitsova, Stoyanka R; Paunova-Krasteva, Tsvetelina S; Pashova, Svetlana B; Angelova, Maria B

2012-12-01

Humicola lutea 103 is a copper-tolerant fungal strain able to grow in the presence of 300 μg·mL(-1) Cu(2+) under submerged cultivation. To prevent the consequences of copper overload, microorganisms have evolved molecular mechanisms that regulate its uptake, intracellular traffic, storage, and efflux. In spite of this avoidance strategy, high heavy-metal concentrations caused distinct and widespread ultrastructural alterations in H. lutea. The mitochondria were the first and main target of the toxic action. The effect of copper on activities of the key enzymes (hexokinase, glucose-6-phosphate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase) included in the 3 main metabolic pathways, glycolysis, pentose phosphate pathway, and tricarboxylic acid cycle, was investigated. High metal concentrations exhibited a dramatic negative effect on hexokinase, while the other 3 enzymes showed a significant and dose-dependent stimulation. On the basis of the present and previous results we concluded that the copper-induced oxidative stress plays an important role in the fungal tolerance to high Cu (2+) concentrations.

Effects of Copper Oxide Nanoparticles on Antioxidant Enzyme Activities and on Tissue Accumulation of Oreochromis niloticus.

PubMed

Tunçsoy, Mustafa; Duran, Servet; Ay, Özcan; Cicik, Bedii; Erdem, Cahit

2017-09-01

Accumulation of copper oxide nanoparticles (CuO NPs) in gill, liver and muscle tissues of Oreochromis niloticus and its effects on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in gill and liver tissues were studied after exposing the fish to 20 µg/L Cu over 15 days. Copper levels and enzyme activities in tissues were determined using spectrophotometric (ICP-AES and UV) techniques respectively. No mortality was observed during the experiments. Copper levels increased in gill and liver tissues of O. niloticus compared to control when exposed to CuO NPs whereas exposure to metal had no effect on muscle level at the end of the exposure period. Highest accumulation of copper was observed in liver while no accumulation was detected in muscle tissue. SOD, CAT activities decreased and GPx activity increased in gill and liver tissues when exposed to CuO NPs.

Lingual dyskinesia and tics: a novel presentation of copper-metabolism disorder.

PubMed

Goez, Helly R; Jacob, Francois D; Yager, Jerome Y

2011-02-01

Copper is a trace element that is required for cellular respiration, neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide amidation, and formation of connective tissue. Abnormalities of copper metabolism have been linked with neurologic disorders that affect movement, such as Wilson disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type copper-metabolism disorders has been more elusive, especially in cases with atypical characteristics. We present here the case of an adolescent with a novel presentation of copper-metabolism disorder who exhibited acute severe hemilingual dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal brain and spinal MRI results and did not show any signs of dysarthria or dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary copper level was elevated after penicillamine challenge. We conclude that copper-metabolism disorders should be included in the differential diagnosis for movement disorders, even in cases with highly unusual presentations, because many of them are treatable. Moreover, a connection between copper-metabolism disorders and tics is presented, to our knowledge, for the first time in humans; further investigation is needed to better establish this connection and understand its underlying pathophysiology.

Role of Copper and Homocysteine in Pressure Overload Heart Failure

PubMed Central

Hughes, William M.; Rodriguez, Walter E.; Rosenberger, Dorothea; Chen, Jing; Sen, Utpal; Tyagi, Neetu; Moshal, Karni S.; Vacek, Thomas; Kang, Y. James

2009-01-01

Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart. PMID:18679830

iron phase control during pressure leaching at elevated temperature

NASA Astrophysics Data System (ADS)

Fleuriault, Camille

Iron is a common contaminant encountered in most metal recovery operations, and particularly hydrometallurgical processes. For example, the Hematite Process uses autoclaves to precipitate iron oxide out of the leaching solution, while other metals are solubilized for further hydrometallurgical processing. In some cases, Basic Iron Sulfate (BIS) forms in place of hematite. The presence of BIS is unwanted in the autoclave discharge because it diminishes recovery and causes environmental matters. The focus of this master thesis is on the various iron phases forming during the pressure oxidation of sulfates. Artificial leaching solutions were produced from CuSO4, FeSO4 and H2SO4 in an attempt to recreate the matrix composition and conditions used for copper sulfides autoclaving. The following factors were investigated in order to determine which conditions hinder the formation of BIS: initial free acidity (5 -- 98 g/L), initial copper concentration (12.7 -- 63.5 g/L), initial iron concentration (16.7 -- 30.7 g/L) and initial iron oxidation state. There were three solid species formed in the autoclave: hematite, BIS and hydronium jarosite. The results show that free acid is the main factor influencing the composition of the residue. At an initial concentration of 22.3 g/L iron and no copper added, the upper limit for iron oxide formation is 41 g/L H2SO4. The increase of BIS content in the residue is not gradual and occurs over a change of a few grams per liter around the aforementioned limit. Increasing copper sulfate concentration in the solution hinders the formation of BIS. At 63.5g/L copper, the upper free acidity limit is increased to 61g/L. This effect seems to be related to the buffering action of copper sulfate, decreasing the overall acid concentration and thus extending the stability range of hematite. The effect of varying iron concentration on the precipitate chemistry is unclear. At high iron levels, the only noticeable effect was the inhibition of jarosite. The results were reported within a Cu-Fe-S ternary system and modeled. The modeling confirmed the experimental observations with the exception that increasing iron concentrations seem to promote BIS stability.

The influence of long-term copper contaminated agricultural soil at different pH levels on microbial communities and springtail transcriptional regulation.

PubMed

de Boer, Tjalf E; Taş, Neslihan; Braster, Martin; Temminghoff, Erwin J M; Röling, Wilfred F M; Roelofs, Dick

2012-01-03

Copper has long been applied for agricultural practises. Like other metals, copper is highly persistent in the environment and biologically active long after its use has ceased. Here we present a unique study on the long-term effects (27 years) of copper and pH on soil microbial communities and on the springtail Folsomia candida an important representative of the soil macrofauna, in an experiment with a full factorial, random block design. Bacterial communities were mostly affected by pH. These effects were prominent in Acidobacteria, while Actinobacteria and Gammaroteobacteria communities were affected by original and bioavailable copper. Reproduction and survival of the collembolan F. candida was not affected by the studied copper concentrations. However, the transcriptomic responses to copper reflected a mechanism of copper transport and detoxification, while pH exerted effects on nucleotide and protein metabolism and (acute) inflammatory response. We conclude that microbial community structure reflected the history of copper contamination, while gene expression analysis of F. candida is associated with the current level of bioavailable copper. The study is a first step in the development of a molecular strategy aiming at a more comprehensive assessment of various aspects of soil quality and ecotoxicology.

The effect of ozonated cooling water on the corrosion behavior of stainless steel, titanium and copper alloys. Ozone biocidal action on sessile and planktonic bacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Videla, H.A.; Guiamet, P.S.; Mele, M.F.L. de

1999-11-01

Two aspects of ozone utilization as sole chemical treatment for cooling water demand a better understanding: (a) the effect of dissolved ozone on the corrosion behavior of heat exchanger structural materials and (b) the biocidal action of ozone on bacterial biofilms. To assess the effect of ozone dissolved in synthetic cooling water on the corrosion behavior of different structural materials (stainless steel; 70:30 copper-nickel; aluminum brass and titanium), voltamperometric experiments and corrosion potential vs. time measurements were made at ozone concentrations between 0.1 and 1.2 ppm. Present results show that the passive behavior of stainless steel and titanium is notmore » affected by dissolved ozone whereas copper alloys are susceptible to corrosion in the presence of ozone. To study the biocidal action of various concentrations of dissolved ozone against planktonic and sessile bacteria, liquid cultures and biofilms of Pseudomonas fluorescense, formed on different structural materials, were used at different contact times. The results show that dissolved ozone is an effective biocide for controlling planktonic cells but its effectiveness decreases in the presence of sessile bacteria and the extracellular polymeric matrix of the biofilm. It is suggested that the penetration of ozone through the biofilm depends on the simultaneous diffusion and reaction of the biocide with the biofilm matrix which may exhibit local differences in biomass distribution and hydrodynamic conditions.« less

Effects of Water Quality and Orthophosphate on Surface Characteristics of Cu Corrosion in Drinking Water using Atomic Force Microscopy

EPA Science Inventory

Since the passage of the Lead and Copper Rule (LCR) in 1991, researchers have examined the effects of water chemistry on the solubility of copper to establish best approaches for reducing copper levels. Despite recent developments, important gaps still exist regarding copper cor...

Insights into the mechanism of copper-tolerance in Fibroporia radiculosa: The biosynthesis of oxalate

Treesearch

Katie Jenkins; Carol A. Clausen; Frederick Green; Susan V. Diehl

2015-01-01

Copper is currently used as the key component in wood preservatives despite the known tolerance of many brown-rot Basidiomycetes. Copper-tolerant fungi, like Fibroporia radiculosa, produce and accumulate high levels of oxalate when exposed to copper. To gain insight into the mechanism of oxalate production, four F. radiculosa...

Circulation of copper in the biotic compartments of a freshwater dammed reservoir.

PubMed

Vinot, I; Pihan, J C

2005-01-01

This study concerns a chronic copper release in an aquatic ecosystem: Mirgenbach reservoir; which is characterized by high salinity, conductivity and hardness, a eutrophic state and a high temperature. To study the bioavailability of copper in the biotic compartments, the sampling covered the entire food chain (phyto- and zooplankton, macroalgae, aquatic plants, crustaceans, mollusks, and fish). Of the organisms present, the filter feeder Dreissena polymorpha, the detritivorous Bithynia tentaculata and Orconectes limosus were most contaminated by copper. The level of copper found in fish was the lowest. Body copper concentrations recorded in the present study show large variability between species even in some that are closely related. In most cases, however, the metal handling strategy, feeding habits, morphology and ecology can, at least partially, explain the metal content recorded. Pollution factors have been used to assess the state of contamination of the food chain. This study showed finally that the copper in the lake is bioavailable and bioaccumulated by organisms up to high levels and some effects of long-term toxicity of copper on benthic community and planktonic biomass were pointed out.

Small molecule glycoconjugates with anticancer activity.

PubMed

Pastuch-Gawołek, Gabriela; Malarz, Katarzyna; Mrozek-Wilczkiewicz, Anna; Musioł, Marta; Serda, Maciej; Czaplinska, Barbara; Musiol, Robert

2016-04-13

Glycoconjugates are combinations of sugar moieties with organic compounds. Due to their biological resemblance, such structures often have properties that are desirable for drugs. In this study we designed and synthesised several glycoconjugates from small molecular quinolines and substituted gluco- and galactopyranosyl amines. Although the parent quinoline compounds were inactive in affordable concentrations, the glycoconjugates that were obtained appeared to be cytotoxic against cancer cells at the micromolar level. When combined with copper ions, their activity increased even further. Their mechanism of action is connected to the formation of reactive oxygen species and the intercalation of DNA. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Enzymatic mechanism of oxalate production in the TCA and glyoxylate pathways using various isolates of Antrodia radiculosa

Treesearch

K.M. Jenkins; S.V. Diehl; C.A. Clausen; F. Green

2011-01-01

Brown-rot fungi produce oxalate in large amounts; however, levels of accumulation and function vary by species. Copper-tolerant fungi, like Antrodia radiculosa, produce and accumulate high levels of oxalate in response to copper. Oxalate biosynthesis in copper-tolerant fungi has been linked to the glyoxylate and tricarboxylic acid (TCA) cycles. Within these two cycles...

Exogenous addition of histidine reduces copper availability in the yeast Saccharomyces cerevisiae.

PubMed

Watanabe, Daisuke; Kikushima, Rie; Aitoku, Miho; Nishimura, Akira; Ohtsu, Iwao; Nasuno, Ryo; Takagi, Hiroshi

2014-07-07

The basic amino acid histidine inhibited yeast cell growth more severely than lysine and arginine. Overexpression of CTR1 , which encodes a high-affinity copper transporter on the plasma membrane, or addition of copper to the medium alleviated this cytotoxicity. However, the intracellular level of copper ions was not decreased in the presence of excess histidine. These results indicate that histidine cytotoxicity is associated with low copper availability inside cells, not with impaired copper uptake. Furthermore, histidine did not affect cell growth under limited respiration conditions, suggesting that histidine cytotoxicity is involved in deficiency of mitochondrial copper.

2016 Draft Estuarine/Marine Copper Aquatic Life Ambient Water Quality Criteria

EPA Pesticide Factsheets

Documents pertain to Aquatic Life Ambient Water Quality criteria for Copper (2016 Estuarine/marine). These documents contain the safe levels of Copper in water that should protect to the majority of species.

Copper in the sediment and sea surface microlayer near a fallowed, open-net fish farm.

PubMed

Loucks, Ronald H; Smith, Ruth E; Fisher, Clyde V; Fisher, E Brian

2012-09-01

Sediment and sea surface microlayer samples near an open-net salmon farm in Nova Scotia, were analysed for copper. Copper is a constituent of the feed and is an active ingredient of anti-foulants. The salmon farm was placed in fallow after 15 years of production. Sampling was pursued over 27 months. Elevated copper concentrations in the sediments indicated the farm site as a source. Bubble flotation due to gas-emitting sediments from eutrophication is a likely process for accumulating copper in the sea surface microlayer at enriched concentrations. Elevated and enriched concentrations in the sea surface microlayer over distance from the farm site led, as a result of wind-drift, to an enlarged farm footprint. The levels of copper in both sediments and sea surface microlayer exceeded guidelines for protection of marine life. Over the 27 months period, copper levels persisted in the sediments and decreased gradually in the sea surface microlayer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Zinc in denture adhesive: a rare cause of copper deficiency in a patient on home parenteral nutrition

PubMed Central

Prasad, Rakesh; Hawthorne, Barney; Durai, Dharmaraj; McDowell, Ian

2015-01-01

A 65-year-old woman with Crohn's disease, who had been on home parenteral nutrition for many years, presented with perioral paraesthesia and a burning sensation in the mouth. Initial blood tests including serum ferritin, vitamin B12 and folate, were normal apart from mild pancytopaenia. Serum copper was low, in spite of receiving regular copper in her parenteral feeds. The copper in her parenteral feeds was increased initially, but when it did not improve, she was started on weekly intravenous copper infusions. She was using dental adhesive, which had zinc in it, and a possibility that this was causing her copper deficiency was raised. Serum zinc levels were normal, but urinary zinc was very high. The patient was advised to use zinc-free dental adhesive and her copper level returned to normal within a few months with normalisation of her pancytopaenia, and partial resolution of her oral paraesthesia. PMID:26452740

Physiological serum copper concentrations found in malignancies cause unfolding induced aggregation of human serum albumin in vitro.

PubMed

Rizvi, Asim; Furkan, Mohd; Naseem, Imrana

2017-12-15

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. Copyright © 2017. Published by Elsevier Inc.

Impact of Plumbing Age on Copper Levels in Drinking Water

EPA Science Inventory

Theory and limited practical experiences suggest that higher copper levels in drinking water tap samples are typically associated with newer plumbing systems, and levels decrease with increasing plumbing age. Past researchers have developed a conceptual model to explain the “agin...

Antioxidative role of nitric oxide on copper toxicity to a chlorophycean alga, Chlorella.

PubMed

Singh, Akhilesh kumar; Sharma, Laxuman; Mallick, Nirupama

2004-10-01

The response of Chlorella vulgaris to copper exposure was investigated under laboratory batch culture conditions. Increased toxicity of Cu with respect to photosynthetic carbon fixation, O(2) evolution, chlorophyll fluorescence, and oxidative burst was observed for N-NH(4)(+)-grown cultures. The addition of sodium nitroprusside, a nitric oxide (NO) donor, in combination with Cu to N-NH(4)(+)-grown Chlorella not only lowered the inhibition levels of carbon fixation, O(2) evolution, and maximum quantum yield of PS II, but also significantly reduced the oxidative burst. The protective action of sodium nitroprusside was, however, arrested in cultures in which sodium nitroprusside was supplemented in combination with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a specific scavenger of NO in the experimental system. The N-NO(3)(-)-grown Chlorella depicted less sensitivity to Cu compared to its N-NH(4)(+)-grown counterpart. The N-NO(3)(-)-, N-NH(4)(+)-, and N-NH(4)(+)+sodium nitroprusside-grown Chlorella did not show any significant differences with respect to their Cu uptake potential. The role of NO as an antioxidant is discussed.

Copper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects.

PubMed

De Riccardis, L; Buccolieri, A; Muci, M; Pitotti, E; De Robertis, F; Trianni, G; Manno, D; Maffia, M

2018-05-01

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. Copyright © 2018 Elsevier B.V. All rights reserved.

Discovery of metabolic signatures for predicting whole organism toxicology.

PubMed

Hines, Adam; Staff, Fred J; Widdows, John; Compton, Russell M; Falciani, Francesco; Viant, Mark R

2010-06-01

Toxicological studies in sentinel organisms frequently use biomarkers to assess biological effect. Development of "omic" technologies has enhanced biomarker discovery at the molecular level, providing signatures unique to toxicant mode-of-action (MOA). However, these signatures often lack relevance to organismal responses, such as growth or reproduction, limiting their value for environmental monitoring. Our primary objective was to discover metabolic signatures in chemically exposed organisms that can predict physiological toxicity. Marine mussels (Mytilus edulis) were exposed for 7 days to 12 and 50 microg/l copper and 50 and 350 microg/l pentachlorophenol (PCP), toxicants with unique MOAs. Physiological responses comprised an established measure of organism energetic fitness, scope for growth (SFG). Metabolic fingerprints were measured in the same individuals using nuclear magnetic resonance-based metabolomics. Metabolic signatures predictive of SFG were sought using optimal variable selection strategies and multivariate regression and then tested upon independently field-sampled mussels from rural and industrialized sites. Copper and PCP induced rational metabolic and physiological changes. Measured and predicted SFG were highly correlated for copper (r(2) = 0.55, P = 2.82 x 10(-7)) and PCP (r(2) = 0.66, P = 3.20 x 10(-6)). Predictive metabolites included methionine and arginine/phosphoarginine for copper and allantoin, valine, and methionine for PCP. When tested on field-sampled animals, metabolic signatures predicted considerably reduced fitness of mussels from the contaminated (SFG = 6.0 J/h/g) versus rural (SFG = 15.2 J/h/g) site. We report the first successful discovery of metabolic signatures in chemically exposed environmental organisms that inform on molecular MOA and that can predict physiological toxicity. This could have far-reaching implications for monitoring impacts on environmental health.

An urgent need to reassess the safe levels of copper in the drinking water: lessons from studies on healthy animals harboring no genetic deficits.

PubMed

Pal, Amit; Jayamani, Jayagandan; Prasad, Rajendra

2014-09-01

Recent seminal studies have established neurodegeneration, cognitive waning and/or β-amyloid deposition due to chronic copper intoxication via drinking water in healthy animals; henceforth, fuelling the debate all again over the safe levels of copper in the drinking water. This review encompasses the contemporary imperative animal studies in which the effect of chronic copper toxicity (especially via drinking water) was evaluated on the central nervous system and memory of uncompromised animals along with discussing the future perspectives. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluating the Mechanism of Oxalate Synthesis of Fibroporia Radiculosa Isolates Adapting to Copper-Tolerance

Treesearch

Katie Marie Jenkins

2012-01-01

Despite the drawbacks associated with tolerant organisms, copper is still used as the key component in current wood preservatives. Copper-tolerant fungi, like Fibroporia radiculosa, produce and accumulate high levels of oxalate in response to copper. The biosynthesis of oxalate has been connected to specific enzymes in the glyoxylate and...

Decreased endometrial HOXA10 expression associated with use of the copper intrauterine-device

PubMed Central

Tetrault, Amy M; Richman, Susan M; Fei, Xiaolan; Taylor, Hugh S

2009-01-01

Objective To characterize human endometrial HOXA10 expression in patients using copper intrauterine devices (IUD). Design Case-control study. Setting Academic medical center Patient(s) Women using copper IUD Interventions(s) Immunohistochemical analysis of endometrial HOXA10 expression in biopsies obtained from 24 women using copper Paraguard T380A as well as in biopsies obtained from 10 normal cycling women who were not using IUD or hormonal contraceptives. Main Outcome Measure(s) Endometrial HOXA10 expression. Result(s) Endometrial HOXA10 expression was markedly decreased in biopsies obtained from women using IUD contraceptive when compared to controls. The mean H score for endometrial stromal cell HOXA10 expression in biopsies obtained from women using Paraguard IUD was 0.21 compared to 2.2 in the control endometrial biopsies (P<0.001). Endometrial glandular expression of HOXA10 was absent in all IUD users. Conclusion(s) Decreased endometrial HOXA10 expression was apparent in women who use a copper IUD. Expression of HOXA10 is essential for endometrial receptivity. A novel mechanism of copper IUD action involves suppression of genes required for endometrial receptivity. The dramatic decrease of endometrial HOXA10 in response to IUD use may contribute to contraceptive efficacy. PMID:18930214

Electrothermal Action of the Pulse of the Current of a Short Artificial-Lightning Stroke on Test Specimens of Wires and Cables of Electric Power Objects

NASA Astrophysics Data System (ADS)

Baranov, M. I.; Rudakov, S. V.

2018-03-01

The authors have given results of investigations of the electrothermal action of aperiodic pulses of temporal shape 10/350 μs of the current of a short artificial-lightning stroke on test specimens of electric wires and cables with copper and aluminum cores and sheaths with polyvinylchloride and polyethylene insulations of power circuits of industrial electric power objects. It has been shown that the thermal stability of such wires and cables is determined by the action integral of the indicated current pulse. The authors have found the maximum permissible and critical densities of this pulse in copper and aluminum current-carrying parts of the wires and cables. High-current experiments conducted under high-voltage laboratory conditions on a unique generator of 10/350 μs pulses of an artificial-lightning current with amplitude-time parameters normalized according to the existing requirements of international and national standards and with tolerances on them have confirmed the reliability of the proposed calculated estimate for thermal lightning resistance of cabling and wiring products.

Electrothermal Action of the Pulse of the Current of a Short Artificial-Lightning Stroke on Test Specimens of Wires and Cables of Electric Power Objects

NASA Astrophysics Data System (ADS)

Baranov, M. I.; Rudakov, S. V.

2018-05-01

The authors have given results of investigations of the electrothermal action of aperiodic pulses of temporal shape 10/350 μs of the current of a short artificial-lightning stroke on test specimens of electric wires and cables with copper and aluminum cores and sheaths with polyvinylchloride and polyethylene insulations of power circuits of industrial electric power objects. It has been shown that the thermal stability of such wires and cables is determined by the action integral of the indicated current pulse. The authors have found the maximum permissible and critical densities of this pulse in copper and aluminum current-carrying parts of the wires and cables. High-current experiments conducted under high-voltage laboratory conditions on a unique generator of 10/350 μs pulses of an artificial-lightning current with amplitude-time parameters normalized according to the existing requirements of international and national standards and with tolerances on them have confirmed the reliability of the proposed calculated estimate for thermal lightning resistance of cabling and wiring products.

Copper toxicology, oxidative stress and inflammation using zebrafish as experimental model.

PubMed

Pereira, Talita Carneiro Brandão; Campos, Maria Martha; Bogo, Maurício Reis

2016-07-01

Copper is an essential micronutrient and a key catalytic cofactor in a wide range of enzymes. As a trace element, copper levels are tightly regulated and both its deficit and excess are deleterious to the organism. Under inflammatory conditions, serum copper levels are increased and trigger oxidative stress responses that activate inflammatory responses. Interestingly, copper dyshomeostasis, oxidative stress and inflammation are commonly present in several chronic diseases. Copper exposure can be easily modeled in zebrafish; a consolidated model in toxicology with increasing interest in immunity-related research. As a result of developmental, economical and genetic advantages, this freshwater teleost is uniquely suitable for chemical and genetic large-scale screenings, representing a powerful experimental tool for a whole-organism approach, mechanistic studies, disease modeling and beyond. Copper toxicological and more recently pro-inflammatory effects have been investigated in both larval and adult zebrafish with breakthrough findings. Here, we provide an overview of copper metabolism in health and disease and its effects on oxidative stress and inflammation responses in zebrafish models. Copper-induced inflammation is highlighted owing to its potential to easily mimic pro-oxidative and pro-inflammatory features that combined with zebrafish genetic tractability could help further in the understanding of copper metabolism, inflammatory responses and related diseases. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Modulation of cholesterol levels in broiler meat by dietary garlic and copper.

PubMed

Konjufca, V H; Pesti, G M; Bakalli, R I

1997-09-01

Male Ross x Ross 208 chickens were fed from hatching to 21 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 0, 1.5, 3.0, and 4.5% of a commercial garlic powder in Experiments 1 and 2. Once the dose-response relationship was established, 3% garlic powder or 63 or 180 mg/kg copper as cupric citrate or cupric sulfate pentahydrate were supplemented to the diet (Experiments 3, 4, 5, and 6). In the first two experiments, reductions of plasma cholesterol (P = 0.006) and triacylglycerols (P = 0.013) and liver (P = 0.012) and breast muscle (P = 0.165) cholesterol were observed in garlic-supplemented birds. Feeding either garlic powder or copper (63 and 180 mg/kg) resulted in reduced levels of plasma cholesterol, liver cholesterol, blood reduced glutathione, and breast and thigh muscle cholesterol. Differences were significant at P < 0.05 in at least one experiment. 3-Hydroxy-3-methylglutaryl reductase activity was decreased due to dietary garlic (P = 0.0369), but not by pharmacological levels of dietary copper (P = 0.982). The activity of fatty acid synthetase was decreased in birds fed copper (P = 0.035). Both garlic and copper supplements decreased cholesterol 7 alpha-hydroxylase activity (P = 0.024 and P = 0.022, respectively). The results of these trials confirm the findings that garlic and copper alter lipid and cholesterol metabolism. However, they do not work by the same mechanism. Feeding dietary garlic or copper for 21 d reduced cholesterol levels of broiler meat without altering growth of the chickens or feed efficiency.

Deficient copper concentrations in dried-defatted hepatic tissue from ob/ob mice: A potential model for study of defective copper regulation in metabolic liver disease.

PubMed

Church, Stephanie J; Begley, Paul; Kureishy, Nina; McHarg, Selina; Bishop, Paul N; Bechtold, David A; Unwin, Richard D; Cooper, Garth J S

2015-05-08

Ob/ob mice provide an animal model for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) in patients with obesity and type-2 diabetes. Low liver copper has been linked to hepatic lipid build-up (steatosis) in animals with systemic copper deficiency caused by low-copper diets. However, hepatic copper status in patients with NAFLD or NASH is uncertain, and a validated animal model useful for the study of hepatic copper regulation in common forms of metabolic liver disease is lacking. Here, we report parallel measurements of essential metal levels in whole-liver tissue and defatted-dried liver tissue from ob/ob and non-obese control mice. Measurements in whole-liver tissue from ob/ob mice at an age when they have developed NAFLD/NASH, provide compelling evidence for factitious lowering of copper and all other essential metals by steatosis, and so cannot be used to study hepatic metal regulation in this model. By marked contrast, metal measurements in defatted-dried liver samples reveal that most essential metals were actually normal and indicate specific lowering of copper in ob/ob mice, consistent with hepatic copper deficiency. Thus ob/ob mice can provide a model useful for the study of copper regulation in NAFLD and NASH, provided levels are measured in defatted-dried liver tissue. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma.

PubMed

Porcu, Cristiana; Antonucci, Laura; Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-02-06

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies.

Altered serum copper homeostasis suggests higher oxidative stress and lower antioxidant capability in patients with chronic hepatitis B.

PubMed

Huang, Yansong; Zhang, Yuan; Lin, Zhexuan; Han, Ming; Cheng, Hongqiu

2018-06-01

Copper homeostasis can be altered by inflammation. This study aimed to investigate the alteration of serum copper homeostasis and to explore its clinical significance in patients with chronic hepatitis B (CHB).Thirty-two patients with CHB and 10 aged- and sex-matched healthy controls were recruited. Analyses included serum levels of total copper (TCu), copper ions (Cu), small molecule copper (SMC), ceruloplasmin (CP), Cu/Zn superoxide dismutase 1 (SOD1), urinary copper, and the activities of serum CP and SOD1.The serum TCu and urinary copper levels in patients with CHB were significantly higher than the controls (P = .04 and .003), while the serum Cu was lower than the controls (P = .0002). CP and SOD1 activities in the serum were significantly lower in patients with CHB compared to controls (P = .005) despite higher serum concentrations. In addition, serum alanine aminotransferase inversely correlated with serum CP activity (P = .0318, r = -0.4065).Serum copper homeostasis was altered in this cohort of patients with CHB. The results suggest increased oxidative stress and impaired antioxidant capability in patients with CHB, in addition to necroinflammation. These results may provide novel insights into the diagnosis and treatment of patients with CHB.

Copper increases the ability of 6-hydroxydopamine to generate oxidative stress and the ability of ascorbate and glutathione to potentiate this effect: potential implications in Parkinson's disease.

PubMed

Cruces-Sande, Antón; Méndez-Álvarez, Estefanía; Soto-Otero, Ramón

2017-06-01

Copper is an essential metal for the function of many proteins related to important cellular reactions and also involved in the synaptic transmission. Although there are several mechanisms involved in copper homeostasis, a dysregulation in this process can result in serious neurological consequences, including degeneration of dopaminergic neurons. 6-Hydroxydopamine is a dopaminergic neurotoxin mainly used in experimental models of Parkinson's disease, whose neurotoxicity has been related to its ability to generate free radicals. In this study, we examined the effects induced by copper on 6-OHDA autoxidation. Our data show that both Cu + and Cu 2+ caused an increase in • OH production by 6-OHDA autoxidation, which was accompanied by an increase in the rate of both p-quinone formation and H 2 O 2 accumulation. The presence of ascorbate greatly enhanced this process by establishing a redox cycle which regenerates 6-OHDA from its p-quinone. However, the presence of glutathione did not change significantly the copper-induced effects. We observed that copper is able to potentiate the ability of 6-OHDA to cause both lipid peroxidation and protein oxidation, with the latter including a reduction in free-thiol content and an increase in carbonyl content. Ascorbate also increases the lipid peroxidation induced by the action of copper and 6-OHDA. Glutathione protects against the copper-induced lipid peroxidation, but does not reduce its potential to oxidize free thiols. These results clearly demonstrate the potential of copper to increase the capacity of 6-OHDA to generate oxidative stress and the ability of ascorbate to enhance this potential, which may contribute to the destruction of dopaminergic neurons. © 2017 International Society for Neurochemistry.

Subchronic treatment of rats with aurothioglucose; effects on plasma, hepatic, renal and urinary zinc, copper and metallothionein.

PubMed

McVety, K J; Shaikh, Z A

1987-11-01

Administration of sodium aurothioglucose (10 mg/kg per day) to female rats for up to 8 weeks resulted in no apparent effects on the kidney. Gold accumulated in kidney, liver, spleen, pancreas, skin and blood. Although plasma and hepatic gold levels increased with time, no remarkable change in either copper, zinc or metallothionein (MT) levels was observed. Gel filtration chromatography of plasma showed binding of gold to albumin, whereas copper was associated with albumin, ceruloplasmin and a protein eluting in the void volume of the Sephadex G-150 column. Almost all of the hepatic gold was bound to proteins other than MT. In the kidney, not only gold but also copper and MT increased rapidly, reached a maximum between 2 and 4 weeks and exhibited insignificant change thereafter. Gold-treated animals showed an increase in binding of copper to the very high molecular weight plasma protein, which may be involved in transport of copper to the kidneys. Urinary gold and MT followed a pattern similar to that in the kidney. Renal zinc also increased but returned to normal by week 8. In renal cytosol 57% and 54% of the gold and copper, respectively, were associated with MT. It appears that the elevated levels of copper and zinc, rather than gold, are responsible for the induction of MT synthesis. This then provides a mechanism by which gold and the inducing metals are retained by the kidney.

Characterization of the yeast copper-inducible promoter system in Arabidopsis thaliana

NASA Technical Reports Server (NTRS)

Granger, C. L.; Cyr, R. J.

2001-01-01

Inducible promoters or gene-switches are used to both spatially and temporally regulate gene expression. Such regulation can provide information concerning the function of a gene in a developmental context as well as avoid potential harmful effects due to overexpression. A gfp construct under the control of a copper-inducible promoter was introduced into Arabidopsis thaliana (L.) Heynh. and the regulatory parameters of this inducible promoter were determined. Here, we describe the time-course of up- and down-regulation of GFP expression in response to copper level, the optimal regulatory levels of copper, and the tissue specificity of expression in three transgenic lines. We conclude that the copper-inducible promoter system may be useful in regulating the time and location of gene expression in A. thaliana.

Laser synthesis of a copper-single-walled carbon nanotube nanocomposite via molecular-level mixing and non-equilibrium solidification

NASA Astrophysics Data System (ADS)

Tu, Jay F.; Rajule, Nilesh; Molian, Pal; Liu, Yi

2016-12-01

A copper-single-walled carbon nanotube (Cu-SWCNT) metal nanocomposite could be an ideal material if it can substantially improve the strength of copper while preserving the metal’s excellent thermal and electrical properties. However, synthesis of such a nanocomposite is highly challenging, because copper and SWCNTs do not form intermetallic compounds and are insoluble; as a result, there are serious issues regarding wettability and fine dispersion of SWCNTs within the copper matrix. In this paper we present a novel wet process, called the laser surface implantation process (LSI), to synthesize Cu-SWCNT nanocomposites by mixing SWCNTs into molten copper. The LSI process includes drilling several microholes on a copper substrate, filling the microholes with SWCNTs suspended in solution, and melting the copper substrate to create a micro-well of molten copper. The molten copper advances radially outward to engulf the microholes with pre-deposited SWCNTs to form the Cu-SWCNT implant upon solidification. Rapid and non-equilibrium solidification is achieved due to copper’s excellent heat conductivity, so that SWCNTs are locked in position within the copper matrix without agglomerating into large clusters. This wet process is very different from the typical dry processes used in powder metallurgy. Very high hardness improvement, up to 527% over pure copper, was achieved, confirmed by micro-indentation tests, with only a 0.23% SWCNT volume fraction. The nanostructure of the nanocomposite was characterized by TEM imaging, energy-dispersive x-ray spectroscopy mapping and spectroscopy measurements. The SWCNTs were found to be finely dispersed within the copper matrix with cluster sizes in the range of nanometers, achieving the goal of molecular-level mixing.

Idiopathic hyperzincemia with associated copper deficiency anemia: a diagnostic dilemma.

PubMed

Merza, Hussein; Sood, Neha; Sood, Raman

2015-10-01

Prompt serum copper and zinc in addition to vitamin B12 levels should be measured in patients suffering from refractory anemia with neurological symptoms. A timely copper supplementation can help revert the hematological and possibly the neurological manifestations.

Response to copper and sodium chloride excess in Spirulina sp. (cyanobacteria).

PubMed

Deniz, F; Saygideger, S D; Karaman, S

2011-07-01

Physiological responses of the cyanobacterium, Spirulina sp., were evaluated following exposure to copper (0.1 and 1.0 mg/L) and sodium chloride (0.2 and 0.4 mol/L) for 7 days. Growth and chlorophyll a content exhibited decreases at most exposure levels, while increases occurred for malondialdehyde at all exposure levels. Proline content was increased at the higher exposure levels. Carotenoid levels of Spirulina sp. were not significantly changed. Increased amounts of malondialdehyde were indicative of free radical formation in Spirulina sp. under the stress, while increasing levels of proline pointed to the occurrence of a scavenging mechanism. Concentrations of copper in Spirulina sp. decreased with increasing concentrations of NaCl.

Time-dependent morphological and biochemical changes following cutaneous thermal burn injury and their modulation by copper nicotinate complex: an animal model.

PubMed

Nassar, Muammar A Y; Eldien, Heba M Saad; Tawab, Hanem S Abdel; Saleem, Tahia H; Omar, Hossam M; Nassar, Ahmed Y; Hussein, Mahmoud Rezk Abdelwahed

2012-10-01

Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

Effects of Copper Pollution on the Phenolic Compound Content, Color, and Antioxidant Activity of Wine.

PubMed

Sun, Xiangyu; Ma, Tingting; Han, Luyang; Huang, Weidong; Zhan, Jicheng

2017-05-03

The effects of copper pollution on the polyphenol content, color, and antioxidant activity of wine, as well as correlations among these factors, were investigated. Copper had clear influences on wine polyphenol content. At low copper concentrations, the concentrations of nearly all polyphenols increased, and the antioxidant activity values of the wine also increased. When the copper concentration reached the lowest level of the medium copper range (9.6~16 mg/L), most of the indices also improved. When the copper concentrations reached the latter part of the medium copper range (19.2 and 22.4 mg/L), many of the tested indices began to decrease. Furthermore, when the copper concentration reached the high ranges (32, 64, and 96 mg/L), the polyphenol content, CIELAB color parameters, and antioxidant activity of wine were substantially decreased, indicating the need to control increasing copper content in grape must.

Cautionary note concerning the CuSO4 X-ray laser. [alternative to lasing action

NASA Technical Reports Server (NTRS)

Billman, K. W.; Mark, H.

1973-01-01

For the so far unconfirmed lasing action claimed by Kepros et al. (1972) to have been obtained by focusing a 1.06-micron radiation of a q-switched Nd(3+) glass laser to a small cylindrical volume inside a CuSO4-doped gelatin medium supported between two glass plates, an alternate explanation is proposed that does not depend on the assumption of laser action in copper. The proposed explanation shows how collimated X-ray beams might be created under the experimental conditions described by Kepros et al.

Use of Fatty Acid Methyl Ester Profiles to Compare Copper-Tolerant and Copper-Sensitive Strains of Pantoea ananatis.

PubMed

Nischwitz, C; Gitaitis, R; Sanders, H; Langston, D; Mullinix, B; Torrance, R; Boyhan, G; Zolobowska, L

2007-10-01

ABSTRACT A survey was conducted to evaluate differences in fatty acid methyl ester (FAME) profiles among strains of Pantoea ananatis, causal agent of center rot of onion (Allium cepa), isolated from 15 different onion cultivars in three different sites in Georgia. Differences in FAME composition were determined by plotting principal components (PCs) in two-dimensional plots. Euclidean distance squared (ED(2)) values indicated a high degree of similarity among strains. Plotting of PCs calculated from P. ananatis strains capable of growing on media amended with copper sulfate pentahydrate (200 mug/ml) indicated that copper-tolerant strains grouped into tight clusters separate from clusters formed by wild-type strains. However, unlike copper-sensitive strains, the copper-tolerant strains tended to cluster by location. A total of 80, 60, and 73% of the strains from Tift1, Tift2, and Tattnall, respectively, exhibited either confluent growth or partial growth on copper-amended medium. However, all strains were sensitive to a mixture of copper sulfate pentahydrate (200 mug/ml) and maneb (40 mug/ml). When copper-tolerant clones were analyzed and compared with their wild-type parents, in all cases the plotting of PCs developed from copper-tolerant clones formed tight clusters separate from clusters formed by the parents. Eigenvalues generated from these tests indicated that two components provided a good summary of the data, accounting for 98, 98, and 96% of the standardized variance for strains Pna 1-15B, Pna 1-12B, and Pna 2-5A, respectively. Furthermore, feature 4 (cis-9-hexadecenoic acid/2-hydroxy-13-methyltetradecanoic acid) and feature 7 (cis-9/trans-12/cis-7-octadecenoic acid) were the highest or second highest absolute values for PC1 in all three strains of the parents versus copper-tolerant clones, and hexadecanoic acid was the highest absolute value for PC2 in all three strains. Along with those fatty acids, dodecanoic acid and feature 3 (3-hydroxytetradecanoic acid/14-methylpentadecenoic acid) also had an impact on the differences observed between copper-sensitive parents and copper-resistant mutants. Finding these changes in bacterial fatty acid composition could lead to the development of a laboratory assay to identify copper-tolerant strains using gas chromatography as well as providing clues to further elucidate the mode of action of copper tolerance.

The association between serum copper concentrations and cardiovascular disease risk factors in children and adolescents in NHANES.

PubMed

Zang, Xiaodong; Huang, Hesuyuan; Zhuang, Zhulun; Chen, Runsen; Xie, Zongyun; Xu, Cheng; Mo, Xuming

2018-06-01

Copper is an essential element in human beings, alterations in serum copper levels could potentially have effect on human health. To date, no data are available regarding how serum copper affects cardiovascular disease (CVD) risk factors in children and adolescents. We examined the association between serum copper levels and CVD risk factors in children and adolescents. We analyzed data consisting of 1427 subjects from a nationally representative sample of the US population in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. The CVD risk factors included total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, fasting glucose, glycohemoglobin, fasting insulin, and blood pressure. Multivariate and generalized linear regressions were performed to investigate associations adjusted for age, gender, ethnicity, poverty:income ratio (PIR), BMI, energy intake, and physical activity. We found significant associations between serum copper and total cholesterol (coefficient = 0.132; 95% CI 0.081, 0.182; P for trend < 0.001), glycohemoglobin (coefficient = 0.044; 95% CI 0.020, 0.069; P < 0.001), and fasting insulin (coefficient = 0.730; 95% CI 0.410, 1.050; P < 0.001) among the included participants. Moreover, in the generalized linear models, subjects with the highest copper levels demonstrated a 0.83% (95% CI 0.44%, 1.24%) greater increase in serum total cholesterol (p for trend < 0.001) when compared to participants with the lowest copper concentrations. Our results provide the first epidemiological evidence that serum copper concentrations are associated with total cholesterol concentrations in children and adolescents. However, the underlying mechanisms still need further exploration.

Copper tolerance in Frankia sp. strain EuI1c involves surface binding and copper transport.

PubMed

Rehan, Medhat; Furnholm, Teal; Finethy, Ryan H; Chu, Feixia; El-Fadly, Gomaah; Tisa, Louis S

2014-09-01

Several Frankia strains have been shown to be copper-tolerant. The mechanism of their copper tolerance was investigated for Frankia sp. strain EuI1c. Copper binding was shown by binding studies. Unusual globular structures were observed on the surface of the bacterium. These globular structures were composed of aggregates containing many relatively smaller "leaf-like" structures. Scanning electron microscopy with energy-dispersive X-ray (SEM-EDAX) analysis of these structures indicated elevated copper and phosphate levels compared to the control cells. Fourier transform infrared spectroscopy (FTIR) analysis indicated an increase in extracellular phosphate on the cell surface of copper-stressed cells. Bioinformatics' analysis of the Frankia sp. strain EuI1c genome revealed five potential cop genes: copA, copZ, copC, copCD, and copD. Experiments with Frankia sp. strain EuI1c using qRT-PCR indicated an increase in messenger RNA (mRNA) levels of the five cop genes upon Cu(2+) stress. After 5 days of Cu(2+) stress, the copA, copZ, copC, copCD, and copD mRNA levels increased 25-, 8-, 18-, 18-, and 25-fold, respectively. The protein profile of Cu(2+)-stressed Frankia sp. strain EuI1c cells revealed the upregulation of a 36.7 kDa protein that was identified as FraEuI1c_1092 (sulfate-binding periplasmic transport protein). Homologues of this gene were only present in the genomes of the Cu(2+)-resistant Frankia strains (EuI1c, DC12, and CN3). These data indicate that copper tolerance by Frankia sp. strain EuI1c involved the binding of copper to the cell surface and transport proteins.

ROS dependent copper toxicity in Hydra-biochemical and molecular study.

PubMed

Zeeshan, Mohammed; Murugadas, Anbazhagan; Ghaskadbi, Surendra; Rajendran, Ramasamy Babu; Akbarsha, Mohammad Abdulkader

2016-01-01

Copper, an essential microelement, is known to be toxic to aquatic life at concentrations higher than that could be tolerated. Copper-induced oxidative stress has been documented in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied in the lower invertebrates. The objective of the present study has been to find the effect of ROS-mediated toxicity of environmentally relevant concentrations of copper at organismal and cellular levels in Hydra magnipapillata. Exposure to copper at sublethal concentrations (0.06 and 0.1mg/L) for 24 or 48h resulted in generation of significant levels of intracellular reactive oxygen species (ROS). We infer that the free radicals here originate predominantly at the lysosomes but partly at the mitochondria also as visualized by H2-DHCFDA staining. Quantitative real-time PCR of RNA extracted from copper-exposed polyps revealed dose-dependent up-regulation of all antioxidant response genes (CAT, SOD, GPx, GST, GR, G6PD). Concurrent increase of Hsp70 and FoxO genes suggests the ability of polyps to respond to stress, which at 48h was not the same as at 24h. Interestingly, the transcript levels of all genes were down-regulated at 48h as compared to 24h incubation period. Comet assay indicated copper as a powerful genotoxicant, and the DNA damage was dose- as well as duration-dependent. Western blotting of proteins (Bax, Bcl-2 and caspase-3) confirmed ROS-mediated mitochondrial cell death in copper-exposed animals. These changes correlated well with changes in morphology, regeneration and aspects of reproduction. Taken together, the results indicate increased production of intracellular ROS in Hydra on copper exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Basis for Antioxidant Enzymes in Mediating Copper Detoxification in the Nematode Caenorhabditis elegans

PubMed Central

Song, Shaojuan; Zhang, Xueyao; Wu, Haihua; Han, Yan; Zhang, Jianzhen; Ma, Enbo; Guo, Yaping

2014-01-01

Antioxidant enzymes play a major role in defending against oxidative damage by copper. However, few studies have been performed to determine which antioxidant enzymes respond to and are necessary for copper detoxification. In this study, we examined both the activities and mRNA levels of SOD, CAT, and GPX under excessive copper stress in Caenorhabditis elegans, which is a powerful model for toxicity studies. Then, taking advantage of the genetics of this model, we assessed the lethal concentration (LC50) values of copper for related mutant strains. The results showed that the SOD, CAT, and GPX activities were significantly greater in treated groups than in controls. The mRNA levels of sod-3, sod-5, ctl-1, ctl-2, and almost all gpx genes were also significantly greater in treated groups than in controls. Among tested mutants, the sod-5, ctl-1, gpx-3, gpx-4, and gpx-6 variants exhibited hypersensitivity to copper. The strains with SOD or CAT over expression were reduced sensitive to copper. Mutations in daf-2 and age-1, which are involved in the insulin/insulin-like growth factor-1 signaling pathway, result in reduced sensitivity to stress. Here, we showed that LC50 values for copper in daf-2 and age-1 mutants were significantly greater than in N2 worms. However, the LC50 values in daf-16;daf-2 and daf-16;age-1 mutants were significantly reduced than in daf-2 and age-1 mutants, implying that reduced copper sensitivity is influenced by DAF-16-related functioning. SOD, CAT, and GPX activities and the mRNA levels of the associated copper responsive genes were significantly increased in daf-2 and age-1 mutants compared to N2. Additionally, the activities of SOD, CAT, and GPX were greater in these mutants than in N2 when treated with copper. Our results not only support the theory that antioxidant enzymes play an important role in copper detoxification but also identify the response and the genes involved in these processes. PMID:25243607

Colloidal and electrochemical aspects of copper-CMP

NASA Astrophysics Data System (ADS)

Sun, Yuxia

Copper based interconnects with low dielectric constant layers are currently used to increase interconnect densities and reduce interconnect time delays in integrated circuits. The technology used to develop copper interconnects involves Chemical Mechanical Planarization (CMP) of copper films deposited on low-k layers (silica or silica based films), which is carried out using slurries containing abrasive particles. One issue using such a structure is copper contamination over dielectric layers (SiO2 film), if not reduced, this contamination will cause current leakage. In this study, the conditions conducive to copper contamination onto SiO2 films during Cu-CMP process were studied, and a post-CMP cleaning technique was discussed based on experimental results. It was found that the adsorption of copper onto a silica surface is kinetically fast (<0.5 minute). The amount of copper absorbed is pH and concentration dependent and affected by presence of H2O2, complexing agents, and copper corrosion inhibitor Benzotrazole. Based on de-sorption results, DI water alone was unable to reduce adsorbed copper to an acceptable level, especially for adsorption that takes place at a higher pH condition. The addition of complex agent, citric acid, proved effective in suppressing copper adsorption onto oxide silica during polishing or post-CMP cleaning by forming stable copper-CA complexes. Surface Complexation Modeling was used to simulate copper adsorption isotherms and predict the copper contamination levels on SiO2 surfaces. Another issue with the application of copper CMP is its environmental impact. CMP is a costly process due to its huge consumption of pure water and slurry. Additionally, Cu-CMP processing generates a waste stream containing certain amounts of copper and abrasive slurry particles. In this study, the separation technique electrocoagulation was investigated to remove both copper and abrasive slurry particles simultaneously. For effluent containing ˜40 ppm dissolved copper, it was found that ˜90% dissolved copper was removed from the waste streams through electroplating and in-situ chemical precipitation. The amount of copper removed through plating is impacted by membrane surface charge, type/amount of complexing agents, and solid content in the slurry suspension. The slurry particles can be removed ˜90% within 2 hours of EC through multiple mechanisms.

Idiopathic hyperzincemia with associated copper deficiency anemia: a diagnostic dilemma

PubMed Central

Merza, Hussein; Sood, Neha; Sood, Raman

2015-01-01

Key Clinical Message Prompt serum copper and zinc in addition to vitamin B12 levels should be measured in patients suffering from refractory anemia with neurological symptoms. A timely copper supplementation can help revert the hematological and possibly the neurological manifestations. PMID:26509015

Validating the use of embryonic fish otoliths as recorders of sublethal exposure to copper in estuarine sediments.

PubMed

Barbee, Nicole C; Greig, Alan; Swearer, Stephen E

2013-07-01

In this study we explore the use of fish otoliths ('earbones') as a tool for detecting exposure to heavy metals in sediments. Because otoliths are metabolically inert and incorporate chemical impurities during growth, they can potentially provide a more permanent record of pollutant exposure history in aquatic environments than soft tissues. To validate this technique we cultured embryos of a native Australian fish, the common Galaxias (Galaxias maculatus), in the laboratory on sediments spiked with copper in a concentration gradient. Our aims were to test whether exposure to copper contaminated sediments is recorded in the otoliths of embryos and determine over what range in concentrations we can detect differences in exposure. We found elevated copper levels in otoliths of embryos exposed to high copper concentrations in sediments, suggesting that otoliths can be used as a tool to track a history of exposure to elevated copper levels in the environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Copper induces expression and methylation changes of early development genes in Crassostrea gigas embryos.

PubMed

Sussarellu, Rossana; Lebreton, Morgane; Rouxel, Julien; Akcha, Farida; Rivière, Guillaume

2018-03-01

Copper contamination is widespread along coastal areas and exerts adverse effects on marine organisms such as mollusks. In the Pacific oyster, copper induces severe developmental abnormalities during early life stages; however, the underlying molecular mechanisms are largely unknown. This study aims to better understand whether the embryotoxic effects of copper in Crassostrea gigas could be mediated by alterations in gene expression, and the putative role of DNA methylation, which is known to contribute to gene regulation in early embryo development. For that purpose, oyster embryos were exposed to 4 nominal copper concentrations (0.1, 1, 10 and 20 μg L -1 Cu 2+ ) during early development assays. Embryotoxicity was monitored through the oyster embryo-larval bioassay at the D-larva stage 24 h post fertilization (hpf) and genotoxicity at gastrulation 7 hpf. In parallel, the relative expression of 15 genes encoding putative homeotic, biomineralization and DNA methylation proteins was measured at three developmental stages (3 hpf morula stage, 7 hpf gastrula stage, 24 hpf D-larvae stage) using RT-qPCR. Global DNA content in methylcytosine and hydroxymethylcytosine were measured by HPLC and gene-specific DNA methylation levels were monitored using MeDIP-qPCR. A significant increase in larval abnormalities was observed from copper concentrations of 10 μg L -1 , while significant genotoxic effects were detected at 1 μg L -1 and above. All the selected genes presented a stage-dependent expression pattern, which was impaired for some homeobox and DNA methylation genes (Notochord, HOXA1, HOX2, Lox5, DNMT3b and CXXC-1) after copper exposure. While global DNA methylation (5-methylcytosine) at gastrula stage didn't show significant changes between experimental conditions, 5-hydroxymethylcytosine, its degradation product, decreased upon copper treatment. The DNA methylation of exons and the transcript levels were correlated in control samples for HOXA1 but such a correlation was diminished following copper exposure. The methylation level of some specific gene regions (HoxA1, Hox2, Engrailed2 and Notochord) displayed changes upon copper exposure. Such changes were gene and exon-specific and no obvious global trends could be identified. Our study suggests that the embryotoxic effects of copper in oysters could involve homeotic gene expression impairment possibly by changing DNA methylation levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma

PubMed Central

Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-01-01

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies. PMID:29507693

Studies on the feeding of cupric sulfate pentahydrate, cupric citrate, and copper oxychloride to broiler chickens.

PubMed

Ewing, H P; Pesti, G M; Bakalli, R I; Menten, J F

1998-03-01

Male commercial broiler strain chickens were fed either a control diet (based on corn and soybean meal) or the control diet supplemented with cupric sulfate pentahydrate, copper oxychloride, or cupric citrate in two experiments conducted in floor pens. In Experiment 1, feeding copper at 125 mg/kg diet for 42 d significantly increased broiler growth; and the response from cupric citrate was significantly better than either cupric sulfate or copper oxychloride. In Experiment 2, the inclusion of copper from cupric citrate was reduced to 63 mg/kg and the length of the experiment was increased to 56 d. Cupric sulfate pentahydrate and copper oxychloride treatments increased weight gain by 4.9% and cupric citrate increased weight gain by 9.1%. The feed conversion ratios (grams of feed:grams of gain of live birds) in the birds fed copper were not significantly different from those fed the basal diet (P > 0.05) unless corrections were made for the weights of the dead birds; the adjusted feed conversion ratios (grams of feed:grams of gain of live birds + grams of gain of mortalities) for the copper-treated birds in Experiments 1 and 2 were 5.2 and 7.6% lower, respectively, than the ratios of birds fed the basal diets. Plasma copper levels increased in supplemented chicks by 35% in Experiment 1 and 24% in Experiment 2. Liver copper levels in both experiments were increased by 26% with copper supplementation. Mortality was not affected by dietary treatment in either experiment (P > 0.05).

In situ antimicrobial behavior of materials with copper-based additives in a hospital environment.

PubMed

Palza, Humberto; Nuñez, Mauricio; Bastías, Roberto; Delgado, Katherine

2018-06-01

Copper and its alloys are effective antimicrobial surface materials in the laboratory and in clinical trials. Copper has been used in the healthcare setting to reduce environmental contamination, and thus prevent healthcare-associated infections, complementing traditional protocols. The addition of copper nanoparticles to polymer/plastic matrices can also produce antimicrobial materials, as confirmed under laboratory conditions. However, there is a lack of studies validating the antimicrobial effects of these nanocomposite materials in clinical trials. To satisfy this issue, plastic waiting room chairs with embedded metal copper nanoparticles, and metal hospital IV pools coated with an organic paint with nanostructured zeolite/copper particles were produced and tested in a hospital environment. These prototypes were sampled once weekly for 10 weeks and the viable microorganisms were analysed and compared with the copper-free materials. In the waiting rooms, chairs with copper reduced by around 73% the total viable microorganisms present, showing activity regardless of the microorganism tested. Although there were only low levels of microorganisms in the IV pools installed in operating rooms because of rigorous hygiene protocols, samples with copper presented lower total viable microorganisms than unfilled materials. Some results did not have statistical significance because of the low load of microorganisms; however, during at least three weeks the IV pools with copper had reduced levels of microorganisms by a statistically significant 50%. These findings show for the first time the feasibility of utilizing the antimicrobial property of copper by adding nanosized fillers to other materials in a hospital environment. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Transcuprein is a Macroglobulin Regulated by Copper and Iron Availability

PubMed Central

Liu, Nanmei; Lo, Louis Shi-li; Askary, S. Hassan; Jones, LaTrice; Kidane, Theodros Z.; Nguyen, Trisha Trang Minh; Goforth, Jeremy; Chu, Yu-Hsiang; Vivas, Esther; Tsai, Monta; Westbrook, Terence; Linder, Maria C.

2009-01-01

SUMMARY Transcuprein is a high affinity copper carrier in the plasma involved in the initial distribution of copper entering the blood from the digestive tract. To identify and obtain cDNA for this protein, it was purified from rat plasma by size exclusion and copper chelate affinity chromatography, and amino acid sequences were obtained. These revealed a 190 kDa glycosylated protein identified as the macroglobulin, α1inhibitorIII, the main macroglobulin of rodent blood plasma. Albumin (65 kDa) co-purified in variable amounts and was concluded to be a contaminant (although it transiently can bind the macroglobulin). The main macroglobulin in human blood plasma (α2-macroglobulin), homologous to α1inhibitorIII, also bound copper tightly. Expression of α1I3 (transcuprein) mRNA by the liver was examined in rats with and without copper deficiency, using quantitative PCR and Northern analysis. Protein expression was examined by Western blotting. Deficient rats with 40% less ceruloplasmin oxidase activity and liver copper concentrations expressed about twice as much α1I3 mRNA, but circulating levels of transcuprein did not differ. Iron deficiency, which increased liver copper concentrations 3-fold, reduced transcuprein mRNA expression and 7circulating levels of transcuprein relative to what occurred in rats with normal or excess iron. We conclude that transcupreins are specific macroglobulins that not only carry zinc but also transport copper in the blood; and that their expression can be modulated by copper and iron availability. PMID:17363239

Effects of copper on growth, metamorphosis and endocrine disruption of Bufo gargarizans larvae.

PubMed

Wang, Chao; Liang, Gang; Chai, Lihong; Wang, Hongyuan

2016-01-01

Chinese toad (Bufo gargarizans) tadpoles were exposed to copper (1, 6.4, 32 and 64μgL(-1) copper) from the beginning of larval period through completion of metamorphosis. We examined the effects of chronic copper exposure on mortality, growth, time to metamorphosis, tail resorption time, body size at the metamorphic climax (Gs 42) and completion of metamorphosis (Gs 46) and thyroid gland histology. In addition, type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were also measured to assess disruption of TH synthesis. Our result showed that 6.4-64μgL(-1) copper concentration increased the mortality and inhibited the growth of B. gargarizans tadpoles. In addition, significant reduction in size at Gs 42 and a time delay to Gs 42 were observed at 6.4-64μgL(-1) copper treatments. Moreover, histological examinations have clearly revealed that 64μgL(-1) copper caused follicular cell hyperplasia in thyroid gland. According to real-time PCR results, exposure to 32 and 64μgL(-1) copper significantly up-regulated mRNA expression of Dio3, but down-regulated mRNA expression of TRα and TRβ mRNA level. We concluded that copper delayed amphibian metamorphosis through changing mRNA expression of Dio3, TRα and TRβ, which suggests that copper might have the endocrine-disrupting effect. Copyright © 2015 Elsevier B.V. All rights reserved.

Screening of Blood Levels of Mercury, Cadmium, and Copper in Pregnant Women in Dakahlia, Egypt: New Attention to an Old Problem.

PubMed

Motawei, Shimaa M; Gouda, Hossam E

2016-06-01

Heavy metals toxicity is a prevalent health problem particularly in developing countries. Mercury and cadmium are toxic elements that have no physiologic functions in human body. They should not be present in the human body by any concentration. Copper, on the other hand, is one of the elements that are essential for normal cell functions and a deficiency as well as an excess of which can cause adverse health effects. To test blood levels of mercury, cadmium, and copper in pregnant women in Dakahlia, Egypt. Using atomic absorption spectrophotometry, blood levels of cadmium, mercury, and copper were measured in 150 pregnant women attending to the antenatal care in Mansoura University Hospital in Dakahlia governorate, Egypt. The mean ± SD of blood mercury, cadmium, and copper levels were found to be far from their levels in the population surveys carried in developed countries like United States of America (USA) and Canada. Heavy metal intoxication and accumulation is a major health hazard. Developing countries, including Egypt, still lack many of the regulatory policies and legislations to control sources of pollution exposure. This should be dealt with in order to solve this problem and limit its health consequences.

Bioaccumulation of metals in plants, arthropods, and mice at a seasonal wetland.

PubMed

Torres, K C; Johnson, M L

2001-11-01

Concentrations of arsenic, cadmium, copper, lead, and nickel were measured in soils, house mice (Mus musculus), and the main food items of this omnivorous mouse to examine the occurrence of these metals in selected components of a seasonal wetland. Soil concentrations of copper, lead, and (in some areas) nickel were elevated, but extractable soil concentrations indicated low bioavailability of metals. Levels of most metals in mice and composited arthropods were consistent with reference site concentrations from other studies. However, copper was found to be particularly mobile within the local ecosystem and accumulated in house mouse carcasses and composited arthropods at substantial levels. Metal residues in Scirpus robustus (alkali bulrush) roots exceeded those in seeds, consistent with patterns of bioaccumulation commonly observed in plants. Uptake and bioaccumulation factors for S. robustus seeds and roots, arthropods, and mouse carcasses and livers are reported. Concentrations of lead and nickel in S. robustus roots exhibited significant linear relationships with levels in soils. Copper levels in S. robustus seeds varied significantly with those in house mouse livers, suggesting that trophic transfer of copper from this food source to mice occurred. However, other spatial patterns of bioaccumulation in S. robustus and house mice relative to soil/seed concentrations were absent. Metal levels in house mice bore no relation to body weight or estimated age.

Differential expression of copper-zinc superoxide dismutase gene of Polygonum sibiricum leaves, stems and underground stems, subjected to high-salt stress.

PubMed

Qu, Chun-Pu; Xu, Zhi-Ru; Liu, Guan-Jun; Liu, Chun; Li, Yang; Wei, Zhi-Gang; Liu, Gui-Feng

2010-01-01

In aerobic organisms, protection against oxidative damage involves the combined action of highly specialized antioxidant enzymes, such as copper-zinc superoxide dismutase. In this work, a cDNA clone which encodes a copper-zinc superoxide dismutase gene, named PS-CuZnSOD, has been identified from P. sibiricum Laxm. by the rapid amplification of cDNA ends method (RACE). Analysis of the nucleotide sequence reveals that the PS-CuZnSOD gene cDNA clone consists of 669 bp, containing 87 bp in the 5' untranslated region; 459 bp in the open reading frame (ORF) encoding 152 amino acids; and 123 bp in 3' untranslated region. The gene accession nucleotide sequence number in GenBank is GQ472846. Sequence analysis indicates that the protein, like most plant superoxide dismutases (SOD), includes two conserved ecCuZnSOD signatures that are from the amino acids 43 to 51, and from the amino acids 137 to 148, and it has a signal peptide extension in the front of the N-terminus (1-16 aa). Expression analysis by real-time quantitative PCR reveals that the PS-CuZnSOD gene is expressed in leaves, stems and underground stems. PS-CuZnSOD gene expression can be induced by 3% NaHCO(3). The different mRNA levels' expression of PS-CuZnSOD show the gene's different expression modes in leaves, stems and underground stems under the salinity-alkalinity stress.

The role of essential trace elements in embryonic and fetal development in livestock.

PubMed

Hostetler, Chris E; Kincaid, Ron L; Mirando, Mark A

2003-09-01

This review addresses the concept that essential trace minerals play a vital role in many enzymatic and metabolic pathways that are critical for conceptus development during pregnancy in livestock species. The conceptus relies entirely on the maternal system for a sufficient supply of trace minerals and other nutrients needed for normal development. If this supply is inadequate, growth and/or health of the conceptus can be affected adversely, and many of these effects carry over into the neonatal period. Information, accumulated in our laboratory and presented herein, indicates that zinc, copper and manganese are among the trace minerals that have the greatest impact on reproduction. For example, levels of zinc, copper and manganese were several fold greater in the conceptus than in other reproductive tissues, indicating that the conceptus preferentially accumulates these minerals, an action that may be important for conceptus development, growth and survival. Moreover, some recent results indicate that increasing the biological availability of zinc, copper and manganese, by attachment to short peptide chains (i.e., proteinated trace minerals) can enhance reproductive performance of swine. Mineral concentrations in conceptuses from female pigs consuming proteinated trace minerals were greater than those from females that consumed only inorganic mineral salts. Elucidating the mechanisms whereby conceptus development and survival are enhanced by essential trace minerals may lead to development of specific feeding programs to increase the number and health of offspring at parturition, thereby allowing for further improvements in production efficiency in animal agriculture.

The Variations of Glycolysis and TCA Cycle Intermediate Levels Grown in Iron and Copper Mediums of Trichoderma harzianum.

PubMed

Tavsan, Zehra; Ayar Kayali, Hulya

2015-05-01

The efficiency of optimal metabolic function by microorganism depends on various parameters, especially essential metal supplementation. In the present study, the effects of iron and copper metals on metabolism were investigated by determination of glycolysis and tricarboxylic acid (TCA) cycle metabolites' levels with respect to the metal concentrations and incubation period in Trichoderma harzianum. The pyruvate and citrate levels of T. harzianum increased up to 15 mg/L of copper via redirection of carbon flux though glycolysis by suppression of pentose phosphate pathway (PPP). However, the α-ketoglutarate levels decreased at concentration higher than 5 mg/L of copper to overcome damage of oxidative stress. The fumarate levels correlated with the α-ketoglutarate levels because of substrate limitation. Besides, in T. harzianum cells grown in various concentrations of iron-containing medium, the intracellular pyruvate, citrate, and α-ketoglutarate levels showed positive correlation with iron concentration due to modifying of expression of glycolysis and TCA cycle enzymes via a mechanism involving cofactor or allosteric regulation. However, as a result of consuming of prior substrates required for fumarate production, its levels rose up to 10 mg/L.

Effect of Zinc and Copper Nanoparticles on Drought Resistance of Wheat Seedlings

NASA Astrophysics Data System (ADS)

Taran, Nataliya; Storozhenko, Volodymyr; Svietlova, Nataliia; Batsmanova, Ludmila; Shvartau, Viktor; Kovalenko, Mariia

2017-01-01

The effect of a colloidal solution of Cu,Zn-nanoparticles on pro-oxidative/antioxidative balance and content of photosynthetic pigments and leaf area of winter wheat plants of steppe (Acveduc) and forest-steppe (Stolichna) ecotypes was investigated in drought conditions. It has been shown that Cu,Zn-nanoparticles decreased the negative effect of drought action upon plants of steppe ecotype Acveduc. In particular, increased activity of antioxidative enzymes reduced the level of accumulation of thiobarbituric acid reactive substances (TBARS) and stabilized the content of photosynthetic pigments and increased relative water content in leaves. Colloidal solution of Cu,Zn-nanoparticles had less significant influence on these indexes in seedlings of the Stolichna variety under drought.

Response to copper of Acidithiobacillus ferrooxidans ATCC 23270 grown in elemental sulfur.

PubMed

Almárcegui, Rodrigo J; Navarro, Claudio A; Paradela, Alberto; Albar, Juan Pablo; von Bernath, Diego; Jerez, Carlos A

2014-11-01

The response of Acidithiobacillus ferrooxidans ATCC 23270 to copper was analyzed in sulfur-grown cells by using quantitative proteomics. Forty-seven proteins showed altered levels in cells grown in the presence of 50 mM copper sulfate. Of these proteins, 24 were up-regulated and 23 down-regulated. As seen before in ferrous iron-grown cells, there was a notorious up-regulation of RND-type Cus systems and different RND-type efflux pumps, indicating that these proteins are very important in copper resistance. Copper also triggered the down-regulation of the major outer membrane porin of A. ferrooxidans in sulfur-grown bacteria, suggesting they respond to the metal by decreasing the influx of cations into the cell. On the contrary, copper in sulfur-grown cells caused an overexpression of putative TadA and TadB proteins known to be essential for biofilm formation in bacteria. Surprisingly, sulfur-grown microorganisms showed increased levels of proteins related with energy generation (rus and petII operons) in the presence of copper. Although rus operon is overexpressed mainly in cells grown in ferrous iron, the up-regulation of rusticyanin in sulfur indicates a possible role for this protein in copper resistance as well. Finally, copper response in A. ferrooxidans appears to be influenced by the substrate being oxidized by the microorganism. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Lipid peroxidation and antioxidant status in workers exposed to PCDD/Fs of metal recovery plants.

PubMed

Chen, Hsiu-Ling; Hsu, Ching-Yi; Hung, Dong-Zong; Hu, Miao-Lin

2006-12-15

Secondary copper smelters, which primarily utilize the waste materials that contain organic impurities, and the zinc recovery plant, which handles mostly fly ash and slag from the iron and steel industry, are major emission sources of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in Taiwan. In this study, we compared the levels of erythrocyte glutathione (GSH), erythrocyte superoxide dismutase (SOD) and plasma malondialdehyde (MDA) in workers at a secondary copper smelting plant and a zinc recovery plant who may have been exposed to PCDD/Fs. Though the PCDD/F levels were higher in workers of zinc recovery plant than those of secondary copper smelting plant, no significant difference was found for serum PCDD/F levels between the two kinds of plants. We observed a significant difference in plasma MDA levels between workers at the zinc recovery plant (2.54 microM) and those at the copper smelting plant (1.79 microM). There was and a significant positive correlation between plasma MDA levels and the PCDD/Fs levels. In addition, we observed that the MDA levels were not affected by smoking and exercise status. Therefore, the data suggest that the MDA levels of the metal recovery workers are influenced by their PCDD/F exposure. The erythrocyte SOD activity in workers from the zinc recovery plant was marginally higher than that from the secondary copper plant (196 vs. 146 units/ml, p<0.06). In both plants, large variations in the MDA and SOD levels were found, especially in the high-PCDD/Fs-exposure group, which may be attributed, at least partially, to the differences in smoking status and the number of cigarettes smoked. Overall, our results indicate a higher oxidative stress in workers of the zinc recovery plant than in workers of the secondary copper smelting plant in Taiwan.

Experimenting with a Visible Copper-Aluminum Displacement Reaction in Agar Gel and Observing Copper Crystal Growth Patterns to Engage Student Interest and Inquiry

ERIC Educational Resources Information Center

Xu, Xinhua; Wu, Meifen; Wang, Xiaogang; Yang, Yangyiwei; Shi, Xiang; Wang, Guoping

2016-01-01

The reaction process of copper-aluminum displacement in agar gel was observed at the microscopic level with a stereomicroscope; pine-like branches of copper crystals growing from aluminum surface into gel at a constant rate were observed. Students were asked to make hypotheses on the pattern formation and design new research approaches to prove…

Phytostabilization potential of evening primrose (Oenothera glazioviana) for copper-contaminated sites.

PubMed

Guo, Pan; Wang, Ting; Liu, Yanli; Xia, Yan; Wang, Guiping; Shen, Zhenguo; Chen, Yahua

2014-01-01

A field investigation, field experiment, and hydroponic experiment were conducted to evaluate feasibility of using Oenothera glazioviana for phytostabilization of copper-contaminated soil. In semiarid mine tailings in Tongling, Anhui, China, O. glazioviana, a copper excluder, was a dominant species in the community, with a low bioaccumulation factor, the lowest copper translocation factor, and the lowest copper content in seed (8 mg kg(-1)). When O. glazioviana was planted in copper-polluted farmland soil in Nanjing, Jiangsu, China, its growth and development improved and the level of γ-linolenic acid in seeds reached 17.1%, compared with 8.73% in mine tailings. A hydroponic study showed that O. glazioviana had high tolerance to copper, low upward transportation capacity of copper, and a high γ-linolenic acid content. Therefore, it has great potential for the phytostabilization of copper-contaminated soils and a high commercial value without risk to human health.

Protective role of quercetin against copper(II)-induced oxidative stress: A spectroscopic, theoretical and DNA damage study.

PubMed

Jomova, Klaudia; Lawson, Michael; Drostinova, Lenka; Lauro, Peter; Poprac, Patrik; Brezova, Vlasta; Michalik, Martin; Lukes, Vladimir; Valko, Marian

2017-12-01

The radical scavenging and metal chelating properties of flavonoids indicate that they may play a protective role in diseases with perturbed metal homeostasis such as Alzheimer's disease. In this work we investigated the effect of the coordination of quercetin to copper(II) in view of the formation of ROS in Cu-catalyzed Fenton reaction. ABTS and DPPH assays confirmed that the copper(II)-quercetin complex exhibits a stronger radical scavenging activity than does quercetin alone. EPR spin trapping experiments have shown that chelation of quercetin to copper significantly suppressed the formation of hydroxyl radicals in the Cu(II)-Fenton reaction. DNA damage experiments revealed a protective effect for quercetin, but only at higher stoichiometric ratios of quercetin relative to copper. DNA protective effect of quercetin against ROS attack was described by two mechanisms. The first mechanism lies in suppressed formation of ROS due to the decreased catalytic action of copper in the Fenton reaction, as a consequence of its chelation and direct scavenging of ROS by free quercetin. Since the Cu-quercetin complex intercalates into DNA, the second mechanism was attributed to a suppressed intercalating ability of the Cu-quercetin complex due to the mildly intercalating free quercetin into DNA, thus creating a protective wall against stronger intercalators. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cellular copper homeostasis: current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases.

PubMed

Bhattacharjee, Ashima; Chakraborty, Kaustav; Shukla, Aditya

2017-10-18

Copper is a trace element essential for almost all living organisms. But the level of intracellular copper needs to be tightly regulated. Dysregulation of cellular copper homeostasis leading to various diseases demonstrates the importance of this tight regulation. Copper homeostasis is regulated not only within the cell but also within individual intracellular compartments. Inactivation of export machinery results in excess copper being redistributed into various intracellular organelles. Recent evidence suggests the involvement of glutathione in playing an important role in regulating copper entry and intracellular copper homeostasis. Therefore interplay of both homeostases might play an important role within the cell. Similar to copper, glutathione balance is tightly regulated within individual cellular compartments. This review explores the existing literature on the role of glutathione in regulating cellular copper homeostasis. On the one hand, interplay of glutathione and copper homeostasis performs an important role in normal physiological processes, for example neuronal differentiation. On the other hand, perturbation of the interplay might play a key role in the pathogenesis of copper homeostasis disorders.

Carbohydrate metabolism in erythrocytes of copper deficient rats.

PubMed

Brooks, S P J; Cockell, K A; Dawson, B A; Ratnayake, W M N; Lampi, B J; Belonje, B; Black, D B; Plouffe, L J

2003-11-01

Dietary copper deficiency is known to adversely affect the circulatory system of fructose-fed rats. Part of the problem may lie in the effect of copper deficiency on intermediary metabolism. To test this, weanling male Long-Evans rats were fed for 4 or 8 weeks on sucrose-based diets containing low or adequate copper content. Copper deficient rats had significantly lower plasma and tissue copper as well as lower plasma copper, zinc-superoxide dismutase activity. Copper deficient rats also had a significantly higher heart:body weight ratio when compared to pair-fed controls. Direct measurement of glycolysis and pentose phosphate pathway flux in erythrocytes using (13)C NMR showed no differences in carbon flux from glucose or fructose to pyruvate but a significantly higher flux through the lactate dehydrogenase locus in copper deficient rats (approximately 1.3 times, average of glucose and glucose + fructose measurements). Copper-deficient animals had significantly higher erythrocyte concentrations of glucose, fructose, glyceraldehyde 3-phosphate and NAD(+). Liver metabolite levels were also affected by copper deficiency being elevated in glycogen and fructose 1-phosphate content. The results show small changes in carbohydrate metabolism of copper deficient rats.

Evaluation of some heavy metals residues in batteries and deep litter rearing systems in Japanese quail meat and offal in Egypt

PubMed Central

Ahmed, Ali M.; Hamed, Dalia M.; Elsharawy, Nagwa T.

2017-01-01

Aim: The main objectives of this study were for comparing the effect of batteries and deep litter rearing systems of domesticated Japanese quail, Coturnix coturnix japonica, on the concentration levels of cadmium, copper, lead, and zinc from the quail meat and offal in Ismailia, Egypt. Materials and Methods: A total of 40 quail meat and their offal samples were randomly collected from two main quail rearing systems: Battery (Group I) and deep litter system (Group II) for determination of concentration levels of cadmium, copper, lead, and zinc. In addition, 80 water and feed samples were randomly collected from water and feeders of both systems in the Food Hygiene Laboratory, Faculty of Veterinary Medicine, Suez Canal University for heavy metals determination. Results: The mean concentration levels of cadmium, copper, lead, and zinc in Group I were 0.010, 0.027, 1.137, and 0.516 ppm and for Group II were 0.093, 0.832, 0.601, and 1.651 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail feed in Group I were 1.114, 1.606, 5.822, and 35.11 ppm and for Group II were 3.010, 2.576, 5.852, and 23.616 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail meat for Group I were 0.058, 5.902, 10.244, and 290 ppm and for Group II were 0.086, 6.092, 0.136, and 1.280 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc for liver samples in Group I were 0.15, 8.32, 1.05, and 3.41 ppm and for Group II were 0.13, 8.88, 0.95, and 4.21 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in kidney samples for the Group I were 0.24, 4.21, 1.96, and 4.03 ppm and for Group II were 0.20, 5.00, 1.56, and 3.78 ppm, respectively. Kidney had the highest concentration levels of heavy metals followed by liver then muscles. The highest concentration levels of copper were observed in liver samples. The order of the levels of these trace elements obtained from the four different quail organs is Ca > Pb > Zn > Cu. Lead and cadmium concentration levels in quail meat samples were exceeded the Egyptian standardization limits and suggesting a health threat from lead and cadmium to the quail consumers. Conclusion: Battery rearing system is more hygienic than deep litter system from the point of heavy metals pollution of water and feeds of quail. Feed samples from battery system had means concentration levels of lead not significantly higher (p>0.05) than those samples from deep litter system. Meanwhile, water samples from battery system had means concentration levels of cadmium, copper, and zinc significantly higher (p>0.05) than those samples from deep litter system. Quail may carry health risks to consumers. PMID:28344413

Evaluation of some heavy metals residues in batteries and deep litter rearing systems in Japanese quail meat and offal in Egypt.

PubMed

Ahmed, Ali M; Hamed, Dalia M; Elsharawy, Nagwa T

2017-02-01

The main objectives of this study were for comparing the effect of batteries and deep litter rearing systems of domesticated Japanese quail, Coturnix coturnix japonica , on the concentration levels of cadmium, copper, lead, and zinc from the quail meat and offal in Ismailia, Egypt. A total of 40 quail meat and their offal samples were randomly collected from two main quail rearing systems: Battery (Group I) and deep litter system (Group II) for determination of concentration levels of cadmium, copper, lead, and zinc. In addition, 80 water and feed samples were randomly collected from water and feeders of both systems in the Food Hygiene Laboratory, Faculty of Veterinary Medicine, Suez Canal University for heavy metals determination. The mean concentration levels of cadmium, copper, lead, and zinc in Group I were 0.010, 0.027, 1.137, and 0.516 ppm and for Group II were 0.093, 0.832, 0.601, and 1.651 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail feed in Group I were 1.114, 1.606, 5.822, and 35.11 ppm and for Group II were 3.010, 2.576, 5.852, and 23.616 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail meat for Group I were 0.058, 5.902, 10.244, and 290 ppm and for Group II were 0.086, 6.092, 0.136, and 1.280 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc for liver samples in Group I were 0.15, 8.32, 1.05, and 3.41 ppm and for Group II were 0.13, 8.88, 0.95, and 4.21 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in kidney samples for the Group I were 0.24, 4.21, 1.96, and 4.03 ppm and for Group II were 0.20, 5.00, 1.56, and 3.78 ppm, respectively. Kidney had the highest concentration levels of heavy metals followed by liver then muscles. The highest concentration levels of copper were observed in liver samples. The order of the levels of these trace elements obtained from the four different quail organs is Ca > Pb > Zn > Cu. Lead and cadmium concentration levels in quail meat samples were exceeded the Egyptian standardization limits and suggesting a health threat from lead and cadmium to the quail consumers. Battery rearing system is more hygienic than deep litter system from the point of heavy metals pollution of water and feeds of quail. Feed samples from battery system had means concentration levels of lead not significantly higher (p>0.05) than those samples from deep litter system. Meanwhile, water samples from battery system had means concentration levels of cadmium, copper, and zinc significantly higher (p>0.05) than those samples from deep litter system. Quail may carry health risks to consumers.

A REVIEW OF ACID COPPER PLATING BATH LIFE EXTENSION AND COPPER RECOVERY FROM ACID COPPER BATHS

EPA Science Inventory

Large quantities of hazardous waste, most in aqueous solution or sludges, are being produced at numerous metal plating and processing facilities in the U.S. Regulatory pressures, future liability, and limited landfill space have driven the cost of metal waste disposal to level...

Control of New Copper Corrosion in High-Alkalinity Drinking Water using Orthophosphate - article

EPA Science Inventory

Research and field experience have shown that high-alkalinity waters can be associated with elevated copper levels in drinking water. The objective of this study was to document the application of orthophosphate to the distribution system of a building with a copper problem asso...

Investigation of the copper contents in vineyard soil, grape must and wine and the relationship among them in the Huaizhuo Basin Region, China: A preliminary study.

PubMed

Sun, Xiangyu; Ma, Tingting; Yu, Jing; Huang, Weidong; Fang, Yulin; Zhan, Jicheng

2018-02-15

The copper contents in vineyard soil, grape must and wine and the relationship among them in the Huaizhuo Basin Region, China, were investigated. The results showed that the copper pollution status in vineyard soils, grapes and wines in the investigated area in China is under control, with only 4 surface soil (0-20cm) samples over maximum residue limits (MRL) and no grape or wine samples over MRL. Different vineyards, grape varieties, vine ages, and training systems all significantly influenced the copper contents in the vineyard soils, grape and wines. Additionally, the copper levels in the vineyard soils, grapes and wines all had some correlation. In wine samples, the copper contents ranged from 0.52 to 663μg/L, which is only approximately one percent the level found in grapes and one ten-thousandth that found in soils. Of the wine samples, red wines showed a significantly higher copper content than white wines, while in the red/white grape and soil samples, no significant differences were observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Copper Pollution Increases the Resistance of Soil Archaeal Community to Changes in Water Regime.

PubMed

Li, Jing; Liu, Yu-Rong; Cui, Li-Juan; Hu, Hang-Wei; Wang, Jun-Tao; He, Ji-Zheng

2017-11-01

Increasing efforts have been devoted to exploring the impact of environmental stresses on soil bacterial communities, but the work on the archaeal community is seldom. Here, we constructed microcosm experiments to investigate the responses of archaeal communities to the subsequent dry-rewetting (DW) disturbance in two contrasting soils (fluvo-aquic and red soil) after 6 years of copper pollution. Ten DW cycles were exerted on the two soils with different copper levels, followed by a 6-week recovery period. In both soils, archaeal diversity (Shannon index) in the high copper-level treatments increased over the incubation period, and archaeal community structure changed remarkably as revealed by the non-metric multidimensional scaling ordinations. In both soils, copper pollution altered the response of dominant operational taxonomic units (OTUs) to the DW disturbance. Throughout the incubation and recovery period, the resistance of archaeal abundance to the DW disturbance was higher in the copper-polluted soils than soils without pollution. Taken together, copper pollution altered the response of soil archaeal diversity and community composition to the DW disturbance and increased the resistance of the archaeal abundance. These findings have important implications for understanding soil microbial responses to ongoing environmental change.

The effects of copper fining on the wine content in sulfur off-odors and on their evolution during accelerated anoxic storage.

PubMed

Vela, Eduardo; Hernández-Orte, Purificación; Franco-Luesma, Ernesto; Ferreira, Vicente

2017-09-15

Three different red wines with reductive character have been treated with two different doses of copper sulfate (0.06 and 0.5mg/L) and with a commercial copper-containing product at the recommended dose (0.6mg/L). Wines were in contact with copper one week, centrifuged and stored at 50°C in strict anoxia for 2weeks (up to 7 in one case). Brine-releasable (BR-) and free fractions of Volatile Sulfur Compounds were determined throughout the process. Relevant increases of BR-H 2 S suggest that those wines contained other H 2 S precursors non-detectable by the brine dilution method. Copper treatments had two major effects: 1) immediate decrease the levels of free H 2 S and methanethiol (MeSH); 2) slow the rate at which free H 2 S (not MeSH) increases during anoxic storage. After 7weeks of anoxia levels of free H 2 S and MeSH were high and similar regardless of the copper treatment. Higher copper doses could induce the accumulation of BR-H 2 S. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fluorescence Lifetime Imaging of Physiological Free Cu(II) Levels in Live Cells with a Cu(II)-Selective Carbonic Anhydrase-Based Biosensor

PubMed Central

McCranor, Bryan J.; Szmacinski, Henryk; Zeng, Hui Hui; Stoddard, A.K.; Hurst, Tamiika; Fierke, Carol A.; Lakowicz, J.R.

2014-01-01

Copper is a required trace element that plays key roles in a number of human enzymes, such that copper deficiency or genetic defects in copper transport lead to serious or fatal disease. Rae, et al., had famously predicted that free copper ion levels in the cell cytoplasm were extremely low, typically too low to be observable. We recently developed a variant of human apocarbonic anhydrase II for sensing metal ions that exhibits 25-fold better selectivity for Cu(II) over Zn(II) than the wild type protein, enabling us to accurately measure Cu(II) in the presence of ordinary cellular (picomolar) concentrations of free zinc. We inserted a fluorescent labeled Cu(II)-specific variant of human apocarbonic anhydrase into PC-12 cells and found that the levels are indeed extremely low (in the femtomolar range). We imaged the free Cu(II) levels in living cells by means of frequency-domain fluorescence lifetime microscopy. Implications of this finding are discussed. PMID:24671220

Regulation of extracellular copper-binding proteins in copper-resistant and copper-sensitive mutants of Vibrio alginolyticus.

PubMed Central

Harwood, V J; Gordon, A S

1994-01-01

Extracellular proteins of wild-type Vibrio alginolyticus were compared with those of copper-resistant and copper-sensitive mutants. One copper-resistant mutant (Cu40B3) constitutively produced an extracellular protein with the same apparent molecular mass (21 kDa) and chromatographic behavior as copper-binding protein (CuBP), a copper-induced supernatant protein which has been implicated in copper detoxification in wild-type V. alginolyticus. Copper-sensitive V. alginolyticus mutants displayed a range of alterations in supernatant protein profiles. CuBP was not detected in supernatants of one copper-sensitive mutant after cultures had been stressed with 50 microM copper. Increased resistance to copper was not induced by preincubation with subinhibitory levels of copper in the wild type or in the copper-resistant mutant Cu40B3. Copper-resistant mutants maintained the ability to grow on copper-amended agar after 10 or more subcultures on nonselective agar, demonstrating the stability of the phenotype. A derivative of Cu40B3 with wild-type sensitivity to copper which no longer constitutively expressed CuBP was isolated. The simultaneous loss of both constitutive CuBP production and copper resistance in Cu40B3 indicates that constitutive CuBP production is necessary for copper resistance in this mutant. These data support the hypothesis that the extracellular, ca. 20-kDa protein(s) of V. alginolyticus is an important factor in survival and growth of the organism at elevated copper concentrations. The range of phenotypes observed in copper-resistant and copper-sensitive V. alginolyticus indicate that altered sensitivity to copper was mediated by a variety of physiological changes. Images PMID:8031076

[Estimation of mercury in the urine of cigarette smokers].

PubMed

Kulikowska-Karpińska, Elżbieta; Zdanowicz, Magdalena; Gałażyn-Sidorczuk, Małgorzata

Cigarette smoking is one of the most common habits of the modern world. According to a NATPOL PLU study, every third adult Pole is dependent on nicotine. Tobacco smoke contains about 5,000 components, of which over 1,000 are very toxic chemical substances (3,4-benzopyrene, heavy metals, free radicals, hydrogen cyanide, nitrogen oxides and N-nitrosamines). Exposure to tobacco smoke is an example of a complex, with a significant number of interactions. To assess the concentration of copper in the urine of smokers. Based on the results, an attempt was made to determine whether smoking can affect the level of copper in the body. The study involved 170 healthy volunteers, 99 smokers and 71 non-smokers (control group). The age of patients in both groups were in the range of 20-60 years. The mean age for men and women was 41 years. The average length of cigarette smoking was 18 years for women and 21 years for men, and the number of cigarettes smoked 1-40 ⁄ 24. The urine concentrations of Cu were determined by atomic absorption spectrometry (AAS) and serum creatinine kinetic method using a set of BIOLAB. Cu concentration in urine was expressed in mg / g creatinine. Smokers were found to have reduced levels of copper in the urine, depending on sex, age and brand of cigarettes. In male smokers, copper concentration in the urine was dependent on age and time of smoking, whereas among women this relationship was not observed. Cigarette smoking significantly influences the level of copper in the urine. Both female and male smokers showed reduced levels of copper in the urine, which may indicate its increased accumulation in the body. Excessive accumulation of copper is very dangerous since it may exhibit toxic effects towards many organs and systems.

Development of a tightly regulated and highly responsive copper-inducible gene expression system and its application to control of flowering time.

PubMed

Saijo, Takanori; Nagasawa, Akitsu

2014-01-01

A newly developed copper-inducible gene expression system overcame the mixed results reported earlier, worked well both in cultured cells and a whole plant, and enabled to control flowering timing. Copper is one of the essential microelements and is readily taken up by plants. However, to date, it has rarely been used to control the expression of genes of interest, probably due to the inefficiency of the gene expression systems. In this study, we successfully developed a copper-inducible gene expression system that is based on the regulation of the yeast metallothionein gene. This system can be applied in the field and regulated at approximately one-hundredth of the rate used for registered copper-based fungicides. In the presence of copper, a translational fusion of the ACE1 transcription factor with the VP16 activation domain (VP16AD) of herpes simplex virus strongly activated transcription of the GFP gene in transgenic Arabidopsis. Interestingly, insertion of the To71 sequence, a 5'-untranslated region of the 130k/180k gene of tomato mosaic virus, upstream of the GFP gene reduced the basal expression of GFP in the absence of copper to almost negligible levels, even in soil-grown plants that were supplemented with ordinary liquid nutrients. Exposure of plants to 100 μM copper resulted in an over 1,000-fold induction ratio at the transcriptional level of GFP. This induction was copper-specific and dose-dependent with rapid and reversible responses. Using this expression system, we also succeeded in regulating floral transition by copper treatment. These results indicate that our newly developed copper-inducible system can accelerate gene functional analysis in model plants and can be used to generate novel agronomic traits in crop species.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarwar, Tarique; Zafaryab, Md; Husain, Mohammed Amir

Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a known antioxidant at lower concentrations, however at higher concentrations or in the presence of metal ions such as copper, it may act as a pro-oxidant. It has been reported that copper levels are significantly raised in different malignancies. Cancer cells are under increased oxidative stress as compared to normal cells. Certain therapeutic substances like polyphenols can further increase this oxidative stress and kill cancer cells without affecting the proliferation of normal cells. Through various in vitro experiments we havemore » shown that the pro-oxidant properties of FA are enhanced in the presence of copper. Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in human peripheral lymphocytes which was ameliorated by specific copper-chelating agent such as neocuproine and scavengers of ROS. This suggested the mobilization of endogenous copper in ROS generation and consequent DNA damage. These results were further validated through cytotoxicity experiments involving different cell lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous copper better explains the anticancer activities of FA. This would be an alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities of FA where it can selectively target cancer cells with elevated levels of copper and ROS. - Highlights: • Pro-oxidant properties of ferulic acid are enhanced in presence of copper. • Ferulic acid causes oxidative DNA damage in lymphocytes as observed by comet assay. • DNA damage was ameliorated by copper chelating agent neocuproine and ROS scavengers. • Endogenous copper is involved in ROS generation causing DNA damage. • Ferulic acid exerts cancer cell specific cytotoxicity as observed by MTT assay.« less

Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia.

PubMed

Xu, Jingshu; Church, Stephanie J; Patassini, Stefano; Begley, Paul; Waldvogel, Henry J; Curtis, Maurice A; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

2017-08-16

Datasets comprising simultaneous measurements of many essential metals in Alzheimer's disease (AD) brain are sparse, and available studies are not entirely in agreement. To further elucidate this matter, we employed inductively-coupled-plasma mass spectrometry to measure post-mortem levels of 8 essential metals and selenium, in 7 brain regions from 9 cases with AD (neuropathological severity Braak IV-VI), and 13 controls who had normal ante-mortem mental function and no evidence of brain disease. Of the regions studied, three undergo severe neuronal damage in AD (hippocampus, entorhinal cortex and middle-temporal gyrus); three are less-severely affected (sensory cortex, motor cortex and cingulate gyrus); and one (cerebellum) is relatively spared. Metal concentrations in the controls differed among brain regions, and AD-associated perturbations in most metals occurred in only a few: regions more severely affected by neurodegeneration generally showed alterations in more metals, and cerebellum displayed a distinctive pattern. By contrast, copper levels were substantively decreased in all AD-brain regions, to 52.8-70.2% of corresponding control values, consistent with pan-cerebral copper deficiency. This copper deficiency could be pathogenic in AD, since levels are lowered to values approximating those in Menkes' disease, an X-linked recessive disorder where brain-copper deficiency is the accepted cause of severe brain damage. Our study reinforces others reporting deficient brain copper in AD, and indicates that interventions aimed at safely and effectively elevating brain copper could provide a new experimental-therapeutic approach.

Studies on the feeding of cupric sulfate pentahydrate and cupric citrate to broiler chickens.

PubMed

Pesti, G M; Bakalli, R I

1996-09-01

Male commercial broiler strain chickens were fed either a control diet (based on corn and soybean meal) or the control diet supplemented with cupric sulfate pentahydrate or cupric citrate in seven experiments (six in floor pens, one in wire-floored batteries). In Experiment 1, feeding 125 or 250 mg/kg copper increased growth (4.9%) and decreased feed conversion ratios (3.4%), total plasma cholesterol (40.2%), and breast muscle cholesterol (37.0%). Feeding 375 mg/kg copper was without further beneficial effect. In Experiment 2, withdrawing growth promoting supplements of copper from the feed for the last 7 d caused a significant (P < 0.05) increase in breast muscle cholesterol at 42 d of age: 57.2, 48.0, and 43.2 mg/100 g meat for birds supplemented for 0, 35, or 42 d, respectively. Feeding 10 vs 260 mg/kg copper caused only small increases in tissue copper levels: 0.36 vs 0.41 mg/kg for breast meat, and 0.48 vs 0.60 mg/kg for thigh meat, respectively. Litter copper accumulations in these experiments were similar to those of earlier reports. Breast muscle cholesterol was reduced by feeding 125 mg/kg supplemental copper from cupric citrate (27.84 mg/100 g) or 125 mg supplemental copper from cupric sulfate pentahydrate (25.32 mg/100 g) compared to broilers fed the control diet (43.92 mg/100 g). Cupric citrate was efficacious for growth promotion at lower copper levels than cupric sulfate pentahydrate, resulting in reduced litter copper.

A Prospective Study of Serum Trace Elements in Healthy Korean Pregnant Women

PubMed Central

Choi, Rihwa; Sun, Jiyu; Yoo, Heejin; Kim, Seonwoo; Cho, Yoon Young; Kim, Hye Jeong; Kim, Sun Wook; Chung, Jae Hoon; Oh, Soo-young; Lee, Soo-Youn

2016-01-01

This prospective study sought to investigate serum levels of trace elements (cobalt, copper, zinc, and selenium) and to assess their effects on pregnancy and neonatal outcomes. Serum levels of trace elements in 245 Korean pregnant women (median gestational age at delivery was 39 + 4 weeks and interquartile range was 38 + 4–40 + 1 weeks) were compared with those of 527 general adults and those of previous studies in other ethnic groups. Pregnancy and neonatal outcomes including gestational diabetes, preeclampsia, neonatal birth weight, and congenital abnormalities were assessed. The median serum trace element concentrations of all pregnant women were: cobalt: 0.39 μg/L (interquartile range, IQR 0.29–0.53), copper: 165.0 μg/dL (IQR 144.0–187.0), zinc: 57.0 μg/dL (IQR 50.0–64.0), and selenium: 94.0 μg/L (IQR 87.0–101.0). Serum cobalt and copper concentrations were higher in pregnant women than in the general population, whereas zinc and selenium levels were lower (p < 0.01). Concentrations of all four trace elements varied significantly during the three trimesters (p < 0.05), and seasonal variation was found in copper, zinc, and selenium, but was not observed for cobalt. The prevalence of preeclampsia was significantly lower with high copper (p = 0.03). Trace element levels varied by pregnancy trimester and season, and alteration in copper status during pregnancy might influence pregnancy outcomes such as preeclampsia. PMID:27886083

A Prospective Study of Serum Trace Elements in Healthy Korean Pregnant Women.

PubMed

Choi, Rihwa; Sun, Jiyu; Yoo, Heejin; Kim, Seonwoo; Cho, Yoon Young; Kim, Hye Jeong; Kim, Sun Wook; Chung, Jae Hoon; Oh, Soo-Young; Lee, Soo-Youn

2016-11-23

This prospective study sought to investigate serum levels of trace elements (cobalt, copper, zinc, and selenium) and to assess their effects on pregnancy and neonatal outcomes. Serum levels of trace elements in 245 Korean pregnant women (median gestational age at delivery was 39 + 4 weeks and interquartile range was 38 + 4-40 + 1 weeks) were compared with those of 527 general adults and those of previous studies in other ethnic groups. Pregnancy and neonatal outcomes including gestational diabetes, preeclampsia, neonatal birth weight, and congenital abnormalities were assessed. The median serum trace element concentrations of all pregnant women were: cobalt: 0.39 μg/L (interquartile range, IQR 0.29-0.53), copper: 165.0 μg/dL (IQR 144.0-187.0), zinc: 57.0 μg/dL (IQR 50.0-64.0), and selenium: 94.0 μg/L (IQR 87.0-101.0). Serum cobalt and copper concentrations were higher in pregnant women than in the general population, whereas zinc and selenium levels were lower ( p < 0.01). Concentrations of all four trace elements varied significantly during the three trimesters ( p < 0.05), and seasonal variation was found in copper, zinc, and selenium, but was not observed for cobalt. The prevalence of preeclampsia was significantly lower with high copper ( p = 0.03). Trace element levels varied by pregnancy trimester and season, and alteration in copper status during pregnancy might influence pregnancy outcomes such as preeclampsia.

Copper tolerance and copper accumulation of herbaceous plants colonizing inactive California copper mines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kruckeberg, A.L.; Wu, L.

1992-06-01

Herbaceous plant species colonizing four copper mine waste sites in northern California were investigated for copper tolerance and copper accumulation. Copper tolerance was found in plant species colonizing soils with high concentrations of soil copper. Seven of the eight plant species tested were found at more than one copper mine. The mines are geographically isolated, which makes dispersal of seeds from one mine to another unlikely. Tolerance has probably evolved independently at each site. The nontolerant field control population of Vulpia microstachya displays significantly higher tolerance to copper at all copper concentration levels tested than the nontolerant Vulpia myrous population,more » and the degree of copper tolerance attained by V. microstachya at the two copper mines was much greater than that found in V. myrous. It suggests that even in these two closely related species, the innate tolerance in their nontolerant populations may reflect their potential for evolution of copper tolerance and their ability to initially colonize copper mine waste sites. The shoot tissue of the copper mine plants of Arenaria douglasii, Bromous mollis, and V. microstachya accumulated less copper than those plants of the same species from the field control sites when the two were grown in identical conditions in nutrient solution containing copper. The root tissue of these mine plants contain more copper than the roots of the nonmine plants. This result suggests that exclusion of copper from the shoots, in part by immobilization in the roots, may be a feature of copper tolerance. No difference in the tissue copper concentration was detected between tolerant and nontolerant plants of Lotus purshianus, Lupinus bicolor, and Trifolium pratense even though the root tissue had more copper than the leaves.« less

The effect of copper(II), iron(II) sulphate, and vitamin C combinations on the weak antimicrobial activity of (+)-catechin against Staphylococcus aureus and other microbes.

PubMed

Holloway, Andrew C; Mueller-Harvey, Irene; Gould, Simon W J; Fielder, Mark D; Naughton, Declan P; Kelly, Alison F

2012-12-01

Few attempts have been made to improve the activity of plant compounds with low antimicrobial efficacy. (+)-Catechin, a weak antimicrobial tea flavanol, was combined with putative adjuncts and tested against different species of bacteria. Copper(II) sulphate enhanced (+)-catechin activity against Pseudomonas aeruginosa but not Staphylococcus aureus, Proteus mirabilis or Escherichia coli. Attempts to raise the activity of (+)-catechin against two unresponsive species, S. aureus and E. coli, with iron(II) sulphate, iron(III) chloride, and vitamin C, showed that iron(II) enhanced (+)-catechin against S. aureus, but not E. coli; neither iron(III) nor combined iron(II) and copper(II), enhanced (+)-catechin activity against either species. Vitamin C enhanced copper(II) containing combinations against both species in the absence of iron(II). Catalase or EDTA added to active samples removed viability effects suggesting that active mixtures had produced H(2)O(2)via the action of added metal(II) ions. H(2)O(2) generation by (+)-catechin plus copper(II) mixtures and copper(II) alone could account for the principal effect of bacterial growth inhibition following 30 minute exposures as well as the antimicrobial effect of (+)-catechin-iron(II) against S. aureus. These novel findings about a weak antimicrobial flavanol contrast with previous knowledge of more active flavanols with transition metal combinations. Weak antimicrobial compounds like (+)-catechin within enhancement mixtures may therefore be used as efficacious agents. (+)-Catechin may provide a means of lowering copper(II) or iron(II) contents in certain crop protection and other products.

Investigation of the interaction of copper(II) oxide and electron beam irradiation crosslinkable polyethylene

NASA Astrophysics Data System (ADS)

Bee, Soo-Tueen; Sin, Lee Tin; Ratnam, C. T.; Haraveen, K. J. S.; Tee, Tiam-Ting; Rahmat, A. R.

2015-10-01

In this study, the effects of electron beam irradiation on the properties of copper(II) oxide when added to low-density polyethylene (LDPE) blends were investigated. It was found that the addition of low loading level of copper(II) oxide (⩽2 phr) to LDPE results in significantly poorer gel content and hot set results. However, the incorporation of higher loading level of copper(II) oxide (⩾3 phr) could slightly increase the degree of crosslinking in all irradiated LDPE composites. This is due to the fact that higher amounts of copper(II) oxide could slightly induce the formation of free radicals in LDPE matrix. Besides, increasing irradiation doses was also found to gradually increase the gel content of LDPE composites by generating higher amounts of free radicals. As a consequence, these higher amounts of free radicals released in the LDPE matrix could significantly increase the degree of crosslinking. The addition of copper(II) oxide could reduce the tensile strength and fracture strain (elongation at break) of LDPE composites because of poorer interfacial adhesion effect between copper(II) oxide particles and LDPE matrix. Meanwhile, increasing irradiation doses on all copper(II) oxide added LDPE composites could marginally increase the tensile strength. In addition, increasing irradiation dose could enhance the thermal stability of LDPE composites by increasing the decomposition temperature. The oxidation induction time (OIT) analysis showed that, because of the crosslinking network in the copper(II) oxide added LDPE composites, oxidation reaction is much delayed.

Interactions between accumulated copper, bacterial community structure and histamine levels in crayfish meat during storage.

PubMed

Soedarini, Bernadeta; van Gestel, Cornelis A M; van Straalen, Nico M; Widianarko, Budi; Röling, Wilfred F M

2014-08-01

Pollution in aquaculture areas may negatively impact edible species and threaten seafood quality and safety. The aim of this study was to determine the interaction between copper and bacteria in the aquatic habitat and their impact upon crustaceans. Marbled crayfish was chosen as a model of aquatic crustaceans and the influence of metal contamination on bacterial community structure in water used to culture crayfish and in crayfish themselves was investigated. Histamine, an allergen commonly formed by certain groups of bacteria in crustacean edible tissue during storage, was also determined. Copper exposure increased its concentration in crayfish meat by 17.4%, but the copper concentration remained within acceptable food safety limits. Elevated copper levels affected the bacterial community both in the water used to cultivate crayfish and in the marbled crayfish themselves. Cluster analysis of 16S rRNA-gene based microbial community fingerprints revealed that copper impacted the bacterial community in the water and in the crayfish meat. However, copper exposure reduced the formation of histamine in crayfish meat during storage by 66.3%. Copper from the habitat appears to reduce histamine accumulation in crayfish meat during storage by affecting the bacterial community structure of the cultivation water and most likely also in the intestine of the crayfish. From a food safety point of view, copper treatment during the aqua culturing of crustaceans has a positive impact on the postharvest stage. © 2013 Society of Chemical Industry.

Inhibition of bacterial biofilms by carboxymethyl chitosan combined with silver, zinc and copper salts.

PubMed

Gonçalves, Randys Caldeira; da Silva, Diego Pereira; Signini, Roberta; Naves, Plínio Lázaro Faleiro

2017-12-01

Investigation of the antimicrobial action of carboxymethyl chitosan (CMCh) is among the alternative approaches in the control of pathogenic microorganisms. This study aimed to screen the toxicity using the brine shrimp lethality assay and to investigate the inhibitory activity of carboxymethyl in isolation or in combination with silver nitrate, copper sulfate and zinc sulfate on biofilm formation by Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Kocuria rhizophila ATCC 9341, Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 25312, and Burkholderia cepacia ATCC 17759. The CMCh was obtained by reacting chitosan with monochloroacetic acid under alkaline conditions, and the occurrence of carboxymethylation was evidenced by FTIR and 1 H NMR spectroscopy. The CMCh was combined with metallic salts (AgNO 3 , CuSO 4 ·5H 2 O and ZnSO 4 ) to perform the bioassays to screen the toxicity, to determine the minimum inhibitory concentration and the impact of sub-inhibitory concentrations against biofilm formation. Although CMCh did not show inhibitory activity against bacterial growth, it had an interesting level of inhibition of bacterial biofilm. The results suggest that sub-inhibitory concentrations of compounds were effective against biofilm formation. Copyright © 2017 Elsevier B.V. All rights reserved.

[IUD-related anatomical, cytological and pathological modifications in the uterine tract (author's transl)].

PubMed

Levrier, M

1982-05-01

This paper presents a study of the anatomical, cytological, and pathological reactions of the vaginal, cervical, and endometrial mucosa in 445 women wearing inert IUDs, copper IUDs, and progesterone-releasing IUDs. Vaginal cytology does not seem to be affected by any type of IUD. Cervical cytology shows with time increased levels of leuko-histiocytosis and at 18 months cellular alterations are evident; in the series presented here after 24 months there were 2% of cases of light or moderate dysplasia. Endometrial cytology shows cellular inflammation, which worsens with time. Endometrial histology shows: 1) for inert IUDs and after 3-4 years of use, a histio-leukocytic action is evident; 2) for copper IUDs there is no particular alteration for the 1st months; after 18-24 months papillary metaplasia is evident; and 3) for progesterone-releasing IUDs a lympho-plasmocytic infiltration is visible in the 1st month of use, with typical hormonal reactions. This study shows that the uterine mucosa is not affected by an IUD for the 1st 2 years of use, after which the signs of inflammatory reaction are minor and common to any IUD type. The regeneration of the mucosa is very quick after IUD removal.

Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry.

PubMed

Wang, F; Jiao, P; Qi, M; Frezza, M; Dou, Q P; Yan, B

2010-01-01

Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.

Economic booms and risky sexual behavior: evidence from Zambian copper mining cities.

PubMed

Wilson, Nicholas

2012-12-01

Existing studies suggest that individual and household level economic shocks affect the demand for and supply of risky sex. However, little evidence exists on the effects of an aggregate shock on equilibrium risky sexual behavior. This paper examines the effects of the early twenty-first century copper boom on risky sexual behavior in Zambian copper mining cities. The results suggest that the copper boom substantially reduced rates of transactional sex and multiple partnerships in copper mining cities. These effects were partly concentrated among young adults and copper boom induced in-migration to mining cities appears to have contributed to these reductions. Copyright © 2012. Published by Elsevier B.V.

Overexpression of amyloid precursor protein increases copper content in HEK293 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suazo, Miriam; Hodar, Christian; Morgan, Carlos

2009-05-15

Amyloid precursor protein (APP) is a transmembrane glycoprotein widely expressed in mammalian tissues and plays a central role in Alzheimer's disease. However, its physiological function remains elusive. Cu{sup 2+} binding and reduction activities have been described in the extracellular APP135-156 region, which might be relevant for cellular copper uptake and homeostasis. Here, we assessed Cu{sup 2+} reduction and {sup 64}Cu uptake in two human HEK293 cell lines overexpressing APP. Our results indicate that Cu{sup 2+} reduction increased and cells accumulated larger levels of copper, maintaining cell viability at supra-physiological levels of Cu{sup 2+} ions. Moreover, wild-type cells exposed to bothmore » Cu{sup 2+} ions and APP135-155 synthetic peptides increased copper reduction and uptake. Complementation of function studies in human APP751 transformed Fre1 defective Saccharomyces cerevisiae cells rescued low Cu{sup 2+} reductase activity and increased {sup 64}Cu uptake. We conclude that Cu{sup 2+} reduction activity of APP facilitates copper uptake and may represent an early step in cellular copper homeostasis.« less

Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus.

PubMed

Mahmoudian, Alireza; Rajaei, Ziba; Haghir, Hossein; Banihashemian, Shahaboldin; Hami, Javad

2012-04-01

The aim of the present study was to determine the effects of valerian (Valeriana officinalis) consumption in pregnancy on cortical volume and the levels of zinc and copper, two essential elements that affect brain development and function, in the brain tissues of mouse fetuses. Pregnant female mice were treated with either saline or 1.2 g/kg body weight valerian extract intraperitoneally daily on gestation days (GD) 7 to 17. On GD 20, mice were sacrificed and their fetuses were collected. Fetal brains were dissected, weighed and processed for histological analysis. The volume of cerebral cortex was estimated by the Cavalieri principle. The levels of zinc and copper in the brain tissues were measured by atomic absorption spectroscopy. The results indicated that valerian consumption in pregnancy had no significant effect on brain weight, cerebral cortex volume and copper level in fetal brain. However,it significantly decreased the level of zinc in the brain (P<0.05). Using valerian during midgestation do not have an adverse effect on cerebral cortex; however,it caused a significant decrease in zinc level in the fetal brain. This suggests that valerian use should be limited during pregnancy.

Restrained management of copper level enhances the antineoplastic activity of imatinib in vitro and in vivo.

PubMed

Hassan, Iftekhar; Khan, Azmat Ali; Aman, Shazia; Qamar, Wajhul; Ebaid, Hossam; Al-Tamimi, Jameel; Alhazza, Ibrahim M; Rady, Ahmed M

2018-01-26

The present study was designed to investigate if elevated copper level can be targeted to enhance the efficacy of a significant anticancer drug, imatinib (ITB). The antineoplastic activity of this drug was assessed in the HepG2, HEK-293, MCF-7 and MDA-MD-231 cells targeting elevated copper level as their common drug target. The cell lines were treated with the different doses of copper chloride (Cu II) and disulfiram (DSF) alone as well as in their combinations with the drug for 24 h in standard culture medium and conditions. The treated cells were subjected to various assays including MTT, PARP, p-53, caspase-7, caspase-3, LDH and single cell electrophoresis. The study shows that DSF and Cu (II) synergizes the anticancer activity of ITB to a significant extent in a dose-specific way as evidenced by the combinations treated groups. Furthermore, the same treatment strategy was employed in cancer-induced rats in which the combinations of ITB-DSF and ITB-Cu II showed enhanced antineoplastic activity as compared to ITB alone. However, DSF was more effective than Cu (II) as an adjuvant to the drug. Hence, restrained manipulation of copper level in tumor cells can orchestrate the redox and molecular dispositions inside the cells favoring the induction of apoptosis.

Systems biology approach in Chlamydomonas reveals connections between copper nutrition and multiple metabolic steps.

PubMed

Castruita, Madeli; Casero, David; Karpowicz, Steven J; Kropat, Janette; Vieler, Astrid; Hsieh, Scott I; Yan, Weihong; Cokus, Shawn; Loo, Joseph A; Benning, Christoph; Pellegrini, Matteo; Merchant, Sabeeha S

2011-04-01

In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O₂-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane protease in the thylakoid suggest a mechanism for blocking copper utilization in the chloroplast. We also found an example of copper sparing in the N assimilation pathway: the replacement of copper amine oxidase by a flavin-dependent backup enzyme. Forty percent of the targets are previously uncharacterized proteins, indicating considerable potential for new discovery in the biology of copper.

NiAl Coatings Investigated for Use in Reusable Launch Vehicles

NASA Technical Reports Server (NTRS)

Raj, Sai V.; Ghosn, Louis J.; Barrett, Charles A.

2003-01-01

As part of its major investment in the area of advanced space transportation, NASA is developing new technologies for use in the second- and third-generation designs of reusable launch vehicles. Among the prototype rocket engines being considered for these launch vehicles are those designed to use liquid hydrogen as the fuel and liquid oxygen as the oxidizer. Advanced copper alloys, such as copper-chromium-niobium (Cu-8(at.%)Cr- 4(at.%)Nb, also referred to as GRCop-84), which was invented at the NASA Glenn Research Center, are being considered for use as liner materials in the combustion chambers and nozzle ramps of these engines. However, previous experience has shown that, in rocket engines using liquid hydrogen and liquid oxygen, copper alloys are subject to a process called blanching, where the material undergoes environmental attack under the action of the combustion gases. In addition, the copper alloy liners undergo thermomechanical fatigue, which often results in an initially square cooling channel deforming into a dog-house shape. Clearly, there is an urgent need to develop new coatings to protect copper liners from environmental attack inside rocket chambers and to lower the temperature of the liners to reduce the probability of deformation and failure by thermomechanical fatigue.

Hydrocarbon-fuel/copper combustion chamber liner compatibility, corrosion prevention, and refurbishment

NASA Technical Reports Server (NTRS)

Rosenberg, S. D.; Gage, M. L.; Homer, G. D.; Franklin, J. E.

1991-01-01

An evaluation is made of combustion product/combustion chamber compatibility in the case of a LOX/liquid hydrocarbon booster engine based on copper-alloy thrust chamber which is regeneratively cooled by the fuel. It is found that sulfur impurities in the fuel are the primary causes of copper corrosion, through formation of Cu2S; sulfur levels as low as 1 ppm can result in sufficiently severe copper corrosion to degrade cooling channel performance. This corrosion can be completely eliminated, however, through the incorporation of an electrodeposited gold coating on the copper cooling-channel walls.

Relation of serum γ-glutamyl transferase activity with copper in an adult population.

PubMed

Peng, You-Fan; Wang, Chun-Fang; Pan, Guo-Gang

2017-10-26

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. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. 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). 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.

An Expanding Range of Functions for the Copper Chaperone/Antioxidant Protein Atox1

PubMed Central

Hatori, Yuta

2013-01-01

Abstract Significance: Antioxidant protein 1 (Atox1 in human cells) is a copper chaperone for the copper export pathway with an essential role in cellular copper distribution. In vitro, Atox1 binds and transfers copper to the copper-transporting ATPases, stimulating their catalytic activity. Inactivation of Atox1 in cells inhibits maturation of secreted cuproenzymes as well as copper export from cells. Recent Advances: Accumulating data suggest that cellular functions of Atox1 are not limited to its copper-trafficking role and may include storage of labile copper, modulation of transcription, and antioxidant defense. The conserved metal binding site of Atox1, CxGC, differs from the metal-binding sites of copper-transporting ATPases and has a physiologically relevant redox potential that equilibrates with the GSH:GSSG pair. Critical Issues: Tight relationship appears to exist between intracellular copper levels and glutathione (GSH) homeostasis. The biochemical properties of Atox1 place it at the intersection of cellular networks that regulate copper distribution and cellular redox balance. Mechanisms through which Atox1 facilitates copper export and contributes to oxidative defense are not fully understood. Future Directions: The current picture of cellular redox homeostasis and copper physiology will be enhanced by further mechanistic studies of functional interactions between the GSH:GSSG pair and copper-trafficking machinery. Antioxid. Redox Signal. 19, 945–957. PMID:23249252

Metallic copper corrosion rates, moisture content, and growth medium influence survival of copper-ion resistant bacteria

PubMed Central

Elguindi, Jutta; Moffitt, Stuart; Hasman, Henrik; Andrade, Cassandra; Raghavan, Srini; Rensing, Christopher

2013-01-01

The rapid killing of various bacteria in contact with metallic copper is thought to be influenced by influx of copper ions into the cells but the exact mechanism is not fully understood. This study showed that the kinetics of contact-killing of copper surfaces depended greatly on the amount of moisture present, copper content of alloys, type of medium used, and type of bacteria. We examined antibiotic- and copper-ion resistant strains of Escherichia coli and Enterococcus faecium isolated from pig farms following the use of copper sulfate as feed supplement. The results showed rapid killing of both copper-ion resistant E. coli and E. faecium strains when samples in rich medium were spread in a thin, moist layer on copper alloys with 85% or greater copper content. E. coli strains were rapidly killed under dry conditions while E. faecium strains were less affected. Electroplated copper surface corrosion rates were determined from electro-chemical polarization tests using the Stern-Geary method and revealed decreased corrosion rates with benzotriazole and thermal oxide coating. Copper-ion resistant E. coli and E. faecium cells suspended in 0.8% NaCl showed prolonged survival rates on electroplated copper surfaces with benzotriazole coating and thermal oxide coating compared to surfaces without anti-corrosion treatment. Control of surface corrosion affected the level of copper ion influx into bacterial cells which contributed directly to bacterial killing. PMID:21085951

Release of Micronized Copper Particles from Pressure ...

EPA Pesticide Factsheets

Micronized copper pressure treated lumber (PTL) has recently been introduced to the consumer market as a replacement for ionized copper PTL. The presence of particulate rather than aqueous copper raises concerns about the exposure of humans as well as the environment to the particles. Two common pathways of exposure, leaching during contact with water and transfer during physical contact, were investigated to gage potential human and environmental risk during intended use of the product. Characterization, leaching tests, and wipe tests were conducted on two representative formulations of micronized copper PTL (micronized copper azole or MCA) to quantify the levels of copper present in the treated material and the amount of copper released during use as well as to determine the form (particle or ion) of the copper after it was released. Additionally, an ionized copper pressure treated wood (alkaline copper azole or ACA) was tested for comparison. The characterization showed that copper carbonate is the primary particle form in the MCA treated wood, but other forms are also present, particularly in the MCA-1 formulation, which contained a large amount of organically complexed copper. Microscopy showed that MCA-1 contained particles roughly half the size of MCA-2. The leaching results indicate that mostly (> ~95%) ionic copper is released from the MCA wood and that the particulate copper that was released is attached to cellulose and not free in solution. A sma

Intracellular Copper Does Not Catalyze the Formation of Oxidative DNA Damage in Escherichia coli▿

PubMed Central

Macomber, Lee; Rensing, Christopher; Imlay, James A.

2007-01-01

Because copper catalyzes the conversion of H2O2 to hydroxyl radicals in vitro, it has been proposed that oxidative DNA damage may be an important component of copper toxicity. Elimination of the copper export genes, copA, cueO, and cusCFBA, rendered Escherichia coli sensitive to growth inhibition by copper and provided forcing circumstances in which this hypothesis could be tested. When the cells were grown in medium supplemented with copper, the intracellular copper content increased 20-fold. However, the copper-loaded mutants were actually less sensitive to killing by H2O2 than cells grown without copper supplementation. The kinetics of cell death showed that excessive intracellular copper eliminated iron-mediated oxidative killing without contributing a copper-mediated component. Measurements of mutagenesis and quantitative PCR analysis confirmed that copper decreased the rate at which H2O2 damaged DNA. Electron paramagnetic resonance (EPR) spin trapping showed that the copper-dependent H2O2 resistance was not caused by inhibition of the Fenton reaction, for copper-supplemented cells exhibited substantial hydroxyl radical formation. However, copper EPR spectroscopy suggested that the majority of H2O2-oxidizable copper is located in the periplasm; therefore, most of the copper-mediated hydroxyl radical formation occurs in this compartment and away from the DNA. Indeed, while E. coli responds to H2O2 stress by inducing iron sequestration proteins, H2O2-stressed cells do not induce proteins that control copper levels. These observations do not explain how copper suppresses iron-mediated damage. However, it is clear that copper does not catalyze significant oxidative DNA damage in vivo; therefore, copper toxicity must occur by a different mechanism. PMID:17189367

Effects of copper on the antioxidant activity of olive polyphenols in bulk oil and oil-in-water emulsions.

PubMed

Paiva-Martins, Fátima; Santos, Vera; Mangericão, Hugo; Gordon, Michael H

2006-05-17

The antioxidant activity and interactions with copper of four olive oil phenolic compounds, namely oleuropein, hydroxytyrosol, 3,4-dihydroxyphenylethanol-elenolic acid (1), and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (2), in olive oil and oil-in-water emulsions stored at 60 degrees C were studied. All four phenolic compounds significantly extended the induction time of lipid oxidation in olive oil with the order of activity being hydroxytyrosol > compound 1 > compound 2 > oleuropein > alpha-tocopherol; but in the presence of Cu(ll), the stability of oil samples containing phenolic compounds decreased by at least 90%, and the antioxidant activity of hydroxytyrosol and compounds 1 and 2 became similar. In oil-in-water emulsions prepared from olive oil stripped of tocopherols, hydroxytyrosol enhanced the prooxidant effect of copper at pH 5.5 but not at pH 7.4. The stability of samples containing copper at pH 5.5 was not significantly different if oleuropein was present from that of the control. Oleuropein at pH 7.4, and compounds 1 and 2 at both pH values tested, reduced the prooxidant effect of copper. The lower stability and the higher reducing capacity of all compounds at pH 7.4 could not explain the higher stability of emulsions containing phenolic compounds at this pH value. However, mixtures containing hydroxytyrosol or oleuropein with copper showed higher 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity at pH 7.4 than at pH 5.5. Moreover, the compound 2-copper complex showed higher radical scavenging activity then the uncomplexed compound at pH 5.5. It can be concluded that the formation of a copper complex with radical scavenging activity is a key step in the antioxidant action of the olive oil phenolic compounds in an emulsion containing copper ions.

The effects of CaEDTA injection on lead, zinc, copper and ALAD in erythrocyte, plasma and urine in lead-exposed workers: a 24-h observation.

PubMed

Aono, H; Araki, S

1984-01-01

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the concentrations of lead, zinc and copper in plasma, erythrocyte and urine, and the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocyte, we administered CaEDTA in 1-h intravenous infusion to ten male gun metal founders with blood-lead concentration of 39 to 64 micrograms/dl (mean 49 micrograms/dl). We found that the plasma concentration of lead, following a rapid rise within the first 3 h, fell temporarily to the level significantly lower than the initial level 19 h after start of the infusion. The plasma concentration of zinc fell to the minimal level 5 h after the infusion; and the erythrocyte concentration of zinc and the ALAD activity concurrently rose to the maximal level 5 h after the infusion. By contrast, no significant alteration was observed in the concentrations of copper in plasma and erythrocyte. The maximal level of urinary metal excretion was attained during the period between 1 and 2 h after start of CaEDTA infusion for lead; within 2 h for zinc; and between 2 and 4 h for copper. The urinary metal excretion returned to the initial level 14 to 24 h after infusion for zinc and copper; but lead excretion was still higher than the initial level during this period. The difference in the kinetics of the three metals following CaEDTA injection is discussed in the light of these findings.

Copper Regulates Cyclic AMP-Dependent Lipolysis

PubMed Central

Krishnamoorthy, Lakshmi; Cotruvo, Joseph A.; Chan, Jefferson; Kaluarachchi, Harini; Muchenditsi, Abigael; Pendyala, Venkata S.; Jia, Shang; Aron, Allegra T.; Ackerman, Cheri M.; Vander Wal, Mark N.; Guan, Timothy; Smaga, Lukas P.; Farhi, Samouil L.; New, Elizabeth J.; Lutsenko, Svetlana; Chang, Christopher J.

2016-01-01

Cell signaling relies extensively on dynamic pools of redox-inactive metal ions such as sodium, potassium, calcium, and zinc, but their redox-active transition metal counterparts such as copper and iron have been studied primarily as static enzyme cofactors. Here we report that copper is an endogenous regulator of lipolysis, the breakdown of fat, which is an essential process in maintaining the body's weight and energy stores. Utilizing a murine model of genetic copper misregulation, in combination with pharmacological alterations in copper status and imaging studies in a 3T3-L1 white adipocyte model, we demonstrate that copper regulates lipolysis at the level of the second messenger, cyclic AMP (cAMP), by altering the activity of the cAMP-degrading phosphodiesterase PDE3B. Biochemical studies of the copper-PDE3B interaction establish copper-dependent inhibition of enzyme activity and identify a key conserved cysteine residue within a PDE3-specific loop that is essential for the observed copper-dependent lipolytic phenotype. PMID:27272565

[Biosorption ability of mutants of Rhodotorula mucilaginosa UCM Y-1776].

PubMed

Mamieieva, O H; Kasatkina, T P; Lavrinchuk, V Ia

2007-01-01

Twenty stable mutants with various coloration intensity have been allocated in carotene-synthesizing natural strain Rhodotorula mucilaginosa UCM Y-1776 (wild type) after nitrosoguanidine action. Two brightly orange mutants 4L and 11 and one non-pigmented mutant 2 were chosen for the further researches. The ultraviolet was inefficient as a mutagen. Resistance to high concentration of copper ions (up to 200 mg/g), high sorption ability (Qmax = 9.1 mmol/g) was characteristic of R. mucilaginosa UCM Y-1776. Concentration of copper ions 50 mg/l was toxic for mutants 4L, 11 and 2, which sorption ability was lower in comparison with carotene pigmented R. mucilaginosa UCM Y-1776. It was shown, for the first time that there was a direct dependence between the presence of carotenoid pigments, resistance to high concentration of copper ions and sorption ability for yeast R. mucilaginosa UCM Y-1776.

Laboratory evolution of copper tolerant yeast strains

PubMed Central

2012-01-01

Background Yeast strains endowed with robustness towards copper and/or enriched in intracellular Cu might find application in biotechnology processes, among others in the production of functional foods. Moreover, they can contribute to the study of human diseases related to impairments of copper metabolism. In this study, we investigated the molecular and physiological factors that confer copper tolerance to strains of baker's yeasts. Results We characterized the effects elicited in natural strains of Candida humilis and Saccharomyces cerevisiae by the exposure to copper in the culture broth. We observed that, whereas the growth of Saccharomyces cells was inhibited already at low Cu concentration, C. humilis was naturally robust and tolerated up to 1 g · L-1 CuSO4 in the medium. This resistant strain accumulated over 7 mg of Cu per gram of biomass and escaped severe oxidative stress thanks to high constitutive levels of superoxide dismutase and catalase. Both yeasts were then "evolved" to obtain hyper-resistant cells able to proliferate in high copper medium. While in S. cerevisiae the evolution of robustness towards Cu was paralleled by the increase of antioxidative enzymes, these same activities decreased in evolved hyper-resistant Candida cells. We also characterized in some detail changes in the profile of copper binding proteins, that appeared to be modified by evolution but, again, in a different way in the two yeasts. Conclusions Following evolution, both Candida and Saccharomyces cells were able to proliferate up to 2.5 g · L-1 CuSO4 and to accumulate high amounts of intracellular copper. The comparison of yeasts differing in their robustness, allowed highlighting physiological and molecular determinants of natural and acquired copper tolerance. We observed that different mechanisms contribute to confer metal tolerance: the control of copper uptake, changes in the levels of enzymes involved in oxidative stress response and changes in the copper-binding proteome. However, copper elicits different physiological and molecular reactions in yeasts with different backgrounds. PMID:22214286

Toxicity and deficiency of copper in Elsholtzia splendens affect photosynthesis biophysics, pigments and metal accumulation.

PubMed

Peng, Hongyun; Kroneck, Peter M H; Küpper, Hendrik

2013-06-18

Elsholtzia splendens is a copper-tolerant plant species growing on copper deposits in China. Spatially and spectrally resolved kinetics of in vivo absorbance and chlorophyll fluorescence in mesophyll of E. splendens were used to investigate the copper-induced stress from deficiency and toxicity as well as the acclimation to excess copper stress. The plants were cultivated in nutrient solutions containing either Fe(III)-EDTA or Fe(III)-EDDHA. Copper toxicity affected light-acclimated electron flow much stronger than nonphotochemical quenching (NPQ) or dark-acclimated photochemical efficiency of PSIIRC (Fv/Fm). It also changed spectrally resolved Chl fluorescence kinetics, in particular by strengthening the short-wavelength (<700 nm) part of NPQ altering light harvesting complex II (LHCII) aggregation. Copper toxicity reduced iron accumulation, decreased Chls and carotenoids in leaves. During acclimation to copper toxicity, leaf copper decreased but leaf iron increased, with photosynthetic activity and pigments recovering to normal levels. Copper tolerance in E. splendens was inducible; acclimation seems be related to homeostasis of copper and iron in E. splendens. Copper deficiency appeared at 10 mg copper per kg leaf DW, leading to reduced growth and decreased photosynthetic parameters (F0, Fv/Fm, ΦPSII). The importance of these results for evaluating responses of phytoremediation plants to stress in their environment is discussed.

The application of the hazard analysis and control points (HACCP) in an ice cream production plant.

PubMed

El-Tawila, M M

1998-01-01

The HACCP system is applied in the present study as a preventive food safety approach to control some hazards appearing in one of the ice cream production plants in Egypt. The problem comprised the presence of bacteriological and some chemical contamination in most of the company products. Before applying the HACCP system, the samples examination showed high total mesophilic plat count in 50% of the samples and high coliform count in all samples compared to the level recommended in the Egyptian standards. The highest staphylococcal count (negative for coagulase test) obtained was that of chocolate (1.3 x 10(4) CFU/g) followed by mango ice cream (l.0 x 10(4) CFU/g). Faecal coliform was only positive in mango ice cream. Additionally, the levels of lead, iron and copper have been determined. Copper was higher than the recommended level in all samples and ranged between 0.46 ppm in pistachio ice cream and 2.48 ppm in chocolate ice cream. Most of the CCPs in the ice cream production were mainly due to improper handling and practices throughout the processing steps and also related to the lack of food hygiene knowledge of the workers. The application of HACCP system has successfully reduced the bacteriological hazards in all samples. After applying the corrective actions, the highest total aerobic plate count (8.0 x 10(4)) was that of Swiss chocolate ice cream which corresponds to 50% of the recommended level by the Egyptian standards. Coliform count was less than 10 in all samples except mango ice cream (43 MPN). A significant decrease in staphylococcal count, faecal coliform and trace metal contamination was also recorded in all samples.

Transcranial Red and Near Infrared Light Transmission in a Cadaveric Model

PubMed Central

Jagdeo, Jared R.; Adams, Lauren E.; Brody, Neil I.; Siegel, Daniel M.

2012-01-01

Background and Objective Low level light therapy has garnered significant interest within the past decade. The exact molecular mechanisms of how red and near infrared light result in physiologic modulation are not fully understood. Heme moieties and copper within cells are red and near infrared light photoreceptors that induce the mitochondrial respiratory chain component cytochrome C oxidase, resulting in a cascade linked to cytoprotection and cellular metabolism. The copper centers in cytochrome C oxidase have a broad absorption range that peaks around 830 nm. Several in vitro and in vivo animal and human models exist that have demonstrated the benefits of red light and near infrared light for various conditions. Clinical applications for low level light therapy are varied. One study in particular demonstrated improved durable functional outcomes status post-stroke in patients treated with near infrared low level light therapy compared to sham treatment [1]. Despite previous data suggesting the beneficial effect in treating multiple conditions, including stroke, with low level light therapy, limited data exists that measures transmission in a human model. Study Design/Materials and Methods To investigate this idea, we measured the transmission of near infrared light energy, using red light for purposes of comparison, through intact cadaver soft tissue, skull bones, and brain using a commercially available LED device at 830 nm and 633 nm. Results Our results demonstrate that near infrared measurably penetrates soft tissue, bone and brain parenchyma in the formalin preserved cadaveric model, in comparison to negligible red light transmission in the same conditions. Conclusion These findings indicate that near infrared light can penetrate formalin fixed soft tissue, bone and brain and implicate that benefits observed in clinical studies are potentially related to direct action of near infrared light on neural tissue. PMID:23077622

Incorporation of copper nanoparticles into paper for point-of-use water purification

PubMed Central

Smith, James A.

2014-01-01

As a cost-effective alternative to silver nanoparticles, we have investigated the use of copper nanoparticles in paper filters for point-of-use water purification. This work reports an environmentally benign method for the direct in situ preparation of copper nanoparticles (CuNPs) in paper by reducing sorbed copper ions with ascorbic acid. Copper nanoparticles were quickly formed in less than 10 minutes and were well distributed on the paper fiber surfaces. Paper sheets were characterized by x-ray diffraction, scanning electron microscopy, energy dispersive x-ray spectroscopy, and atomic absorption spectroscopy. Antibacterial activity of the CuNP sheets was assessed for by passing Escherichia coli bacteria suspensions through the papers. The effluent was analyzed for viable bacteria and copper release. The CuNP papers with higher copper content showed a high bacteria reduction of log 8.8 for E. coli. The paper sheets containing copper nanoparticles were effective in inactivating the test bacteria as they passed through the paper. The copper levels released in the effluent water were below the recommended limit for copper in drinking water (1 ppm). PMID:25014431

Photosynthesis Involvement in the Mechanism of Action of Diphenyl Ether Herbicides 1

PubMed Central

Ensminger, Michael P.; Hess, F. Dan

1985-01-01

Photosynthesis is not required for the toxicity of diphenyl ether herbicides, nor are chloroplast thylakoids the primary site of diphenyl ether herbicide activity. Isolated spinach (Spinacia oleracea L.) chloroplast fragments produced malonyl dialdehyde, indicating lipid peroxidation, when paraquat (1,1′-dimethyl-4,4′-bipyridinium ion) or diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] were added to the medium, but no malonyl dialdehyde was produced when chloroplast fragments were treated with the methyl ester of acifluorfen (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid), oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene], or MC15608 (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-chlorobenzoate). In most cases the toxicity of acifluorfen-methyl, oxyfluorfen, or MC15608 to the unicellular green alga Chlamydomonas eugametos (Moewus) did not decrease after simultaneous treatment with diuron. However, diuron significantly reduced cell death after paraquat treatment at all but the highest paraquat concentration tested (0.1 millimolar). These data indicate electron transport of photosynthesis is not serving the same function for diphenyl ether herbicides as for paraquat. Additional evidence for differential action of paraquat was obtained from the superoxide scavenger copper penicillamine (copper complex of 2-amino-3-mercapto-3-methylbutanoic acid). Copper penicillamine eliminated paraquat toxicity in cucumber (Cucumis sativus L.) cotyledons but did not reduce diphenyl ether herbicide toxicity. PMID:16664206

Photosynthesis involvement in the mechanism of action of diphenyl ether herbicides.

PubMed

Ensminger, M P; Hess, F D

1985-05-01

Photosynthesis is not required for the toxicity of diphenyl ether herbicides, nor are chloroplast thylakoids the primary site of diphenyl ether herbicide activity. Isolated spinach (Spinacia oleracea L.) chloroplast fragments produced malonyl dialdehyde, indicating lipid peroxidation, when paraquat (1,1'-dimethyl-4,4'-bipyridinium ion) or diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] were added to the medium, but no malonyl dialdehyde was produced when chloroplast fragments were treated with the methyl ester of acifluorfen (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid), oxyfluorfen [2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene], or MC15608 (methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-chlorobenzoate). In most cases the toxicity of acifluorfen-methyl, oxyfluorfen, or MC15608 to the unicellular green alga Chlamydomonas eugametos (Moewus) did not decrease after simultaneous treatment with diuron. However, diuron significantly reduced cell death after paraquat treatment at all but the highest paraquat concentration tested (0.1 millimolar). These data indicate electron transport of photosynthesis is not serving the same function for diphenyl ether herbicides as for paraquat. Additional evidence for differential action of paraquat was obtained from the superoxide scavenger copper penicillamine (copper complex of 2-amino-3-mercapto-3-methylbutanoic acid). Copper penicillamine eliminated paraquat toxicity in cucumber (Cucumis sativus L.) cotyledons but did not reduce diphenyl ether herbicide toxicity.

Molecular control of copper homeostasis in filamentous fungi: increased expression of a metallothionein gene during aging of Podospora anserina.

PubMed

Averbeck, N B; Borghouts, C; Hamann, A; Specke, V; Osiewacz, H D

2001-01-01

The lifespan of the ascomycete Podospora anserina was previously demonstrated to be significantly increased in a copper-uptake mutant, suggesting that copper is a potential stressor involved in degenerative processes. In order to determine whether changes in copper stress occur in the cells during normal aging of cultures, we cloned and characterized a gene coding for a component of the molecular machinery involved in the control of copper homeostasis. This gene, PaMt1, is a single-copy gene that encodes a metallothionein of 26 amino acids. The coding sequence of PaMt1 is interrupted by a single intron. The deduced amino acid sequence shows a high degree of sequence identity to metallothioneins of the filamentous ascomycete Neurospora crassa and the basidiomycete Agaricus bisporus, and to the N-terminal portion of mammalian metallothioneins. Levels of PaMt1 transcript increase in response to elevated amounts of copper in the growth medium and during aging of wild-type cultures. In contrast, in the long-lived mutant grisea, transcript levels first increase but then decrease again. The ability of wild-type cultures to respond to exogenous copper stress via the induction of PaMt1 transcription is not affected as they grow older.

Efficacy of copper borax preservative against wood decay

Treesearch

William Abbott; Bessie Woodward; Michael West

2001-01-01

In this study, a wood preservative containing active ingredients of 43.5% borax and 3.1% copper hydroxide was evaluated in soil-block tests in accordance with AWPA E10. Results suggested thatthe copper hydroxide was not contributing to fungal toxicity at preservative threshold levels. Thresholds determined for this preservative were very close to those previously...

NA{sup +}, K{sup +}-ATPase, histopathological, and genetic responses of Corbicula fluminea to sediment-associated copper

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, S.

1995-12-31

Time-dependent responses to sediment-associated copper were studies at hierarchical levels of biological organization along an extreme concentration gradient (40 to 40,000 mg/kg total Cu). Laboratory and in situ estimates of molecular to tissue-level responses (Na/K-ATPase activity, DNA content, histopathology) were monitored in Corbicula fluminea (Asiatic clam), and compared with laboratory and field based survival of Corbicula and Elimia teres (an indigenous Gastropoda). Mollusc survival was, in turn, compared with effects on macrobenthic community composition along the stream/[Cu] gradient. Relationships between selected sediment characteristics and the bioavailability and toxicity of sediment associated copper were also investigated. Sediment-associated copper depressed Na/K-ATPase activitymore » and led to histopathological damage of renal and gill epithelia (vacuolization, degeneration), indicating that impaired ion regulation was an important mechanism of toxicity. Concurrent reductions in DNA content were believed to be secondary effects due to cell death, not an indication of genotoxicity. Sublethal responses were significantly correlated with survival in both species; however, while survival in situ was indicative of differences in community structure, laboratory-based survival was not. Copper levels in tissues were indicative of exposure, but were not significantly correlated with adverse effects. Copper levels in sediments, interstitial water, and overlying water varied independently of sediment characteristics except pH. Cu/AVS ratios were predictive of Corbicula and Elimia survival, but were not significantly related to differences in community structure. Instead, macrobenthic community structure was influenced by other sediment factors (grain size, Eh, pH).« less

High serum copper level is associated with an increased risk of preeclampsia in Asians: A meta-analysis.

PubMed

Song, Xingxing; Li, Bingrong; Li, Zongyao; Wang, Jiantao; Zhang, Dongfeng

2017-03-01

Epidemiological studies evaluating the associations between serum copper and ratios of Cu/Zn and the preeclampsia (PE) risk in Asian population have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize the relationships. We hypothesize that higher serum copper and ratios of Cu/Zn may increase the PE risk. A systematic literature search was performed in PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), VIP (Database of Chinese Scientific and Technical Periodicals) and Wangfang databases for relevant studies up to November 2016. Pooled standardized mean difference (SMD) was calculated with random effects model. The results showed that PE patients had a higher serum copper level [SMD (95% CI): 1.05 (0.34, 1.77), Z=2.88, P for Z=0.004; I 2 =96.9%, P for I 2 <0.0001] compared with healthy pregnancy controls. In subgroup analyses, a higher serum copper level in PE patients was observed in case-control studies [SMD (95% CI): 1.39 (0.44, 2.34)]. No significant difference was found between PE patients and healthy pregnancy controls for ratios of Cu/Zn [(SMD (95% CI): 0.26 (-0.77, 1.29), Z=0.49, P for Z=0.625; I 2 =95.8%, P for I 2 <0.0001)]. In conclusion, our meta-analysis indicates that a higher serum copper level is associated with an increased risk of PE. Further studies are needed to confirm these results in future research. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of copper supplement on growth and viability of strains used as starters and adjunct cultures for Emmental cheese manufacture.

PubMed

Rodríguez, L Mato; Alatossava, T

2008-10-01

To determine the effects of supplemented copper (Cu2+) on growth and viability of strains used as starters and adjunct cultures for Emmental cheese manufacture. Thirteen strains belonging to Lactobacillus delbrueckii, Lactobacillus helveticus, Lactobacillus rhamnosus, Streptococcus thermophilus or Propionibacterium freudenreichii species were exposed to various copper concentrations in the proper growth medium at relevant growth temperatures, and the effects of supplemented copper on bacterial growth and cell viability were determined by optical density and pH measurements, also by platings. Among the species considered, L. delbrueckii was the most copper resistant and S. thermophilus the most sensitive to copper. Anaerobic conditions increased this sensitivity significantly. There was also a considerable amount of variation in copper resistance at strain level. Copper resistance is both a species- and strain-dependent property and may reflect variability in copper-binding capacities by cell wall components among species and strains. In addition, the chemical state of copper may be involved. This study revealed that copper resistance is a highly variable property among starter and adjunct strains, and this variability should be considered when strains are selected for Emmental cheese manufacture.

Textured carbon on copper: A novel surface with extremely low secondary electron emission characteristics

NASA Technical Reports Server (NTRS)

Curren, A. N.; Jensen, K. A.

1985-01-01

Experimentally determined values of true secondary electron emission and relative values of reflected primary electron yield for a range of primary electron beam energies and beam impingement angles are presented for a series of novel textured carbon surfaces on copper substrates. (All copper surfaces used in this study were oxygen-free, high-conductivity grade). The purpose of this investigation is to provide information necessary to develop high-efficiency multistage depressed collectors (MDC's) for microwave amplifier traveling-wave tubes (TWT's) for communications and aircraft applications. To attain the highest TWT signal quality and overall efficiency, the MDC electrode surface must have low secondary electron emission characteristics. While copper is the material most commonly used for MDC electrodes, it exhibits relatively high levels of secondary electron emission unless its surface is treated for emission control. The textured carbon surface on copper substrate described in this report is a particularly promising candidate for the MDC electrode application. Samples of textured carbon surfaces on copper substrates typical of three different levels of treatment are prepared and tested for this study. The materials are tested at primary electron beam energies of 200 to 2000 eV and at direct (0 deg) to near-grazing (85 deg) beam impingement angles. True secondary electron emission and relative reflected primary electron yield characteristics of the textured surfaces are compared with each other and with those of untreated copper. All the textured carbon surfaces on copper substrate tested exhibited sharply lower secondary electron emission characteristics than those of an untreated copper surface.

Serum zinc, copper and iron status of children with coeliac disease on three months of gluten-free diet with or without four weeks of zinc supplements: a randomised controlled trial.

PubMed

Negi, K; Kumar, R; Sharma, L; Datta, S P; Choudhury, M; Kumar, P

2018-04-01

Data about the effect of zinc supplementation with gluten-free diet on normalisation of plasma zinc, copper and iron in patients with coeliac disease are scanty. We evaluated the effect of zinc supplementation on serum zinc, copper and iron levels in patients with coeliac disease, by randomising 71 children newly diagnosed with coeliac disease into two groups: Group A = gluten-free diet (GFD); and Group B = gluten-free diet with zinc supplements (GFD +Zn). The rise in iron and zinc was significantly higher in the latter, but the mean rise of copper levels was slightly higher in the former, but the difference was not significant.

Anti-emetic principles of Poria cocos.

PubMed

Tai, T; Akita, Y; Kinoshita, K; Koyama, K; Takahashi, K; Watanabe, K

1995-12-01

The triterpenes isolated from P. cocos and their derivatives were examined for anti-emetic activity. Some of these triterpenes inhibited emetic action induced by oral administration of copper sulfate pentahydrate to leopard frog. The triterpenes having an exomethylene group at C-24 showed anti-emetic activity to frogs.

The effects of low-level ionizing radiation and copper exposure on the incidence of antibiotic resistance in lentic biofilm bacteria.

PubMed

McArthur, J Vaun; Dicks, Christian A; Bryan, A Lawrence; Tuckfield, R Cary

2017-09-01

Environmental reservoirs of antibiotic resistant bacteria are poorly understood. Understanding how the environment selects for resistance traits in the absence of antibiotics is critical in developing strategies to mitigate this growing menace. Indirect or co-selection of resistance by environmental pollution has been shown to increase antibiotic resistance. However no attention has been given to the effects of low-level ionizing radiation or the interactions between radiation and heavy metals on the maintenance or selection for antibiotic resistance (AR) traits. Here we explore the effect of radiation and copper on antibiotic resistance. Bacteria were collected from biofilms in two ponds - one impacted by low-level radiocesium and the other an abandoned farm pond. Through laboratory controlled experiments we examined the effects of increasing concentrations of copper on the incidence of antibiotic resistance. Differences were detected in the resistance profiles of the controls from each pond. Low levels (0.01 mM) of copper sulfate increased resistance but 0.5 mM concentrations of copper sulfate depressed the AR response in both ponds. A similar pattern was observed for levels of multiple antibiotic resistance per isolate. The first principal component response of isolate exposure to multiple antibiotics showed significant differences among the six isolate treatment combinations. These differences were clearly visualized through a discriminant function analysis, which showed distinct antibiotic resistance response patterns based on the six treatment groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systems Biology Approach in Chlamydomonas Reveals Connections between Copper Nutrition and Multiple Metabolic Steps[C][W][OA

PubMed Central

Castruita, Madeli; Casero, David; Karpowicz, Steven J.; Kropat, Janette; Vieler, Astrid; Hsieh, Scott I.; Yan, Weihong; Cokus, Shawn; Loo, Joseph A.; Benning, Christoph; Pellegrini, Matteo; Merchant, Sabeeha S.

2011-01-01

In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane protease in the thylakoid suggest a mechanism for blocking copper utilization in the chloroplast. We also found an example of copper sparing in the N assimilation pathway: the replacement of copper amine oxidase by a flavin-dependent backup enzyme. Forty percent of the targets are previously uncharacterized proteins, indicating considerable potential for new discovery in the biology of copper. PMID:21498682

Effects of an aged copper contamination on distribution of earthworms, reproduction and cocoon hatchability.

PubMed

Mirmonsef, Hassan; Hornum, Hanne D; Jensen, John; Holmstrup, Martin

2017-01-01

Contaminated soil is a problem throughout the industrialized world, and a significant proportion of these sites are polluted with heavy metals such as copper. Ecological risk assessment of contaminated sites requires ecotoxicological studies with spiked soils as well as in-situ ecological observations. Here, we report laboratory and field assessment of copper toxicity for earthworms at a Danish site (Hygum) exclusively contaminated with an increasing gradient in copper from background to highly toxic levels (>1000mgkg -1 dry soil). More specifically, we report effects on field populations, body contents of copper, hatching of earthworm cocoons and reproduction of the common species Aporrectodea tuberculata. Abundance of earthworms and cocoons decreased significantly from about 400-150m -2 along the gradient as the soil copper concentration increased from ca. 50 to ca. 1000mgkg -1 . At lower concentrations, the population was dominated by endogeic species, whereas at high concentrations the population was dominated by epigeic species. At high copper contents the internal concentration of copper was in the range 100-160mgkg -1 dry tissue. Despite the high internal copper contents, hatchability of field collected cocoons was not impaired in any species. The EC50 reproduction value of A. tuberculata was about 220mg copper kg -1 dry soil in the first two exposure periods, but nearly doubled in the third period suggesting that an acclimation response had occurred. Also in the laboratory reproduction test, cocoon hatchability was not reduced, but rather slightly stimulated by copper. Based on these results we discuss the possibility that acute exposure in laboratory experiments is more detrimental than exposure in a field situation, perhaps because increased tolerance may be acquired through natural selection and genetic adaptation through increased use of defense mechanisms such as metallothioneins. Further, we discuss that the rather high tissue copper level of earthworms from the Hygum site may have smaller effects in these free-ranging worms than it would have in acute-exposure laboratory tests because the copper is more efficiently sequestered and detoxified in the field situation where populations have been exposed for many generations. Copyright © 2016 Elsevier Inc. All rights reserved.

Juvenile roach (Rutilus rutilus) increase their anaerobic metabolism in response to copper exposure in laboratory conditions.

PubMed

Maes, Virginie; Betoulle, Stéphane; Jaffal, Ali; Dedourge-Geffard, Odile; Delahaut, Laurence; Geffard, Alain; Palluel, Olivier; Sanchez, Wilfried; Paris-Palacios, Séverine; Vettier, Aurélie; David, Elise

2016-07-01

This study aims to determine the potential impairment of cell energy synthesis processes (glycolysis and respiratory chain pathways) by copper in juvenile roach at different regulation levels by using a multi-marker approach. Juvenile roach were exposed to 0, 10, 50, and 100 µg/L of copper for 7 days in laboratory conditions. The glycolysis pathway was assessed by measuring the relative expression levels of 4 genes encoding glycolysis enzymes. The respiratory chain was studied by assessing the electron transport system and cytochrome c oxidase gene expression. Muscle mitochondria ultrastructure was studied, and antioxidant responses were measured. Furthermore, the main energy reserves-carbohydrates, lipids, and proteins-were measured, and cellular energy was evaluated by measuring ATP, ADP, AMP and IMP concentrations. This study revealed a disturbance of the cell energy metabolism due to copper exposure, with a significant decrease in adenylate energy charge in roach exposed to 10 μg/L of copper after 1 day. Moreover, ATP concentrations significantly decreased in roach exposed to 10 μg/L of copper after 1 day. This significant decrease persisted in roach exposed to 50 µg/L of copper after 7 days. AMP concentrations increased in all contaminated fish after 1 day of exposure. In parallel, the relative expression of 3 genes encoding for glycolysis enzymes increased in all contaminated fish after 1 day of copper exposure. Focusing on the respiratory chain, cytochrome c oxidase gene expression also increased in all contaminated fish at the two time-points. The activity of the electron transport system was not disturbed by copper, except in roach exposed to 100 µg/L of copper after 1 day. Copper induced a metabolic stress. Juvenile roach seemed to respond to the ensuing high energy demand by increasing their anaerobic metabolism, but the energy produced by the anaerobic metabolism is unable to compensate for the stress induced by copper after 7 days. This multi-marker approach allows us to reach a greater understanding of the effects of copper on the physiological responses of juvenile roach.

Activation of Cu,Zn-superoxide dismutase in the absence of oxygen and the copper chaperone CCS.

PubMed

Leitch, Jeffry M; Jensen, Laran T; Bouldin, Samantha D; Outten, Caryn E; Hart, P John; Culotta, Valeria C

2009-08-14

Eukaryotic Cu,Zn-superoxide dismutases (SOD1s) are generally thought to acquire the essential copper cofactor and intramolecular disulfide bond through the action of the CCS copper chaperone. However, several metazoan SOD1s have been shown to acquire activity in vivo in the absence of CCS, and the Cu,Zn-SOD from Caenorhabditis elegans has evolved complete independence from CCS. To investigate SOD1 activation in the absence of CCS, we compared and contrasted the CCS-independent activation of C. elegans and human SOD1 to the strict CCS-dependent activation of Saccharomyces cerevisiae SOD1. Using a yeast expression system, both pathways were seen to acquire copper derived from cell surface transporters and compete for the same intracellular pool of copper. Like CCS, CCS-independent activation occurs rapidly with a preexisting pool of apo-SOD1 without the need for new protein synthesis. The two pathways, however, strongly diverge when assayed for the SOD1 disulfide. SOD1 molecules that are activated without CCS exhibit disulfide oxidation in vivo without oxygen and under copper-depleted conditions. The strict requirement for copper, oxygen, and CCS in disulfide bond oxidation appears exclusive to yeast SOD1, and we find that a unique proline at position 144 in yeast SOD1 is responsible for this disulfide effect. CCS-dependent and -independent pathways also exhibit differential requirements for molecular oxygen. CCS activation of SOD1 requires oxygen, whereas the CCS-independent pathway is able to activate SOD1s even under anaerobic conditions. In this manner, Cu,Zn-SOD from metazoans may retain activity over a wide range of physiological oxygen tensions.

Effects of Copper Addition on Copper Resistance, Antibiotic Resistance Genes, and intl1 during Swine Manure Composting

PubMed Central

Yin, Yanan; Gu, Jie; Wang, Xiaojuan; Song, Wen; Zhang, Kaiyu; Sun, Wei; Zhang, Xin; Zhang, Yajun; Li, Haichao

2017-01-01

Copper is one of the most abundant heavy metals present in swine manure. In this study, a laboratory-scale aerobic composting system was amended with Cu at three levels (0, 200, and 2000 mg kg-1, i.e., control, Cu200, and Cu2000 treatments, respectively) to determine its effect on the fate of copper resistance genes [copper resistance genes (CRGs): pcoA, cusA, copA, and tcrB], antibiotic resistance genes [antibiotic resistance genes (ARGs): erm(A) and erm(B)], and intl1. The results showed that the absolute abundances of pcoA, tcrB, erm(A), erm(B), and intl1 were reduced, whereas those of copA and cusA increased after swine manure composting. Redundancy analysis showed that temperature significantly affected the variations in CRGs, ARGs, and intl1. The decreases in CRGs, ARGs, and intI1 were positively correlated with the exchangeable Cu levels. The bacterial community could be grouped according to the composting time under different treatments, where the high concentration of copper had a more persistent effect on the bacterial community. Network analysis determined that the co-occurrence of CRGs, ARGs, and intI1, and the bacterial community were the main contributors to the changes in CRGs, ARG, and intl1. Thus, temperature, copper, and changes in the bacterial community composition had important effects on the variations in CRGs, ARGs, and intl1 during manure composting in the presence of added copper. PMID:28316595

Subacute copper-deficiency myelopathy in a patient with occult celiac disease.

PubMed

Cavallieri, Francesco; Fini, Nicola; Contardi, Sara; Fiorini, Massimo; Corradini, Elena; Valzania, Franco

2017-07-01

Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms.

Copper speciation in the gill microenvironment of carp (Cyprinus carpio) at various levels of pH.

PubMed

Tao, Shu; Long, Aimin; Xu, Fuliu; Dawson, R W

2002-07-01

The fish gill microenvironment of Cyprinus carpio under stress of copper exposure was investigated. pH and other parameters including free copper activity, alkalinity, and inorganic and organic carbons in the surrounding water (inspired water) and in the gill microenvironment (expired water) were measured or calculated at various levels of pH and varying total copper concentrations. The chemical equilibrium calculation (from MINEQA2) and complexation modeling (mucus-copper) were coupled to calculate both species distribution. The results indicate that the pH in the fish gill microenvironment was different from that in the surrounding water with a balance point around 6.9. The secretion of both CO(2) and mucus was affected in both linear and nonlinear ways when the fish were exposed to elevated concentrations of copper. The complexation capacity of the gill mucus was characterized by a conditional stability constant (logk(Cu-mucus)) of 5.37 along with a complexation equivalent concentration (L(Cu-mucus)) of 0.96 mmol Cu/mg C. For both the fish microenvironment and the surrounding water, the dominant copper species shifted from Cu(2+) to CuCO(3)(0) and to Cu(OH)(2)(0) when the pH of the surrounding water changed from 6.12 to 8.11. The change in copper speciation in the gill microenvironment is smaller than that in the surrounding water due to the pH buffering capacity of the fish gills.

Isolating metal-tolerant bacteria capable of removing copper, chromium, and arsenic from treated wood

Treesearch

Carol A. Clausen

2000-01-01

Bioremediation of chromated copper arsenate-treated waste wood with one or more metal-tolerant bacteria is a potential method of naturally releasing metals from treated wood fibre. Sampling eight environments with elevated levels of copper, chromium, and arsenic resulted in the isolation of 28 bacteria with the capability of releasing one or more of the components from...

High copper level comulled and impregnated sulfur sorbent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, K.C.

A porous sulfur sorbent is disclosed which has principal use in desulfurizing reformer feedstreams. The sorbent is prepared by peptizing alumina with acid and mulling the peptized alumina with a copper compound to form an extrudable dough. The dough is extruded, dried and impregnated with additional copper. The resulting sorbent has a higher capacity for adsorbing sulfur compounds than conventional prior art materials.

Copper homeostasis gene discovery in Drosophila melanogaster.

PubMed

Norgate, Melanie; Southon, Adam; Zou, Sige; Zhan, Ming; Sun, Yu; Batterham, Phil; Camakaris, James

2007-06-01

Recent studies have shown a high level of conservation between Drosophila melanogaster and mammalian copper homeostasis mechanisms. These studies have also demonstrated the efficiency with which this species can be used to characterize novel genes, at both the cellular and whole organism level. As a versatile and inexpensive model organism, Drosophila is also particularly useful for gene discovery applications and thus has the potential to be extremely useful in identifying novel copper homeostasis genes and putative disease genes. In order to assess the suitability of Drosophila for this purpose, three screening approaches have been investigated. These include an analysis of the global transcriptional response to copper in both adult flies and an embryonic cell line using DNA microarray analysis. Two mutagenesis-based screens were also utilized. Several candidate copper homeostasis genes have been identified through this work. In addition, the results of each screen were carefully analyzed to identify any factors influencing efficiency and sensitivity. These are discussed here with the aim of maximizing the efficiency of future screens and the most suitable approaches are outlined. Building on this information, there is great potential for the further use of Drosophila for copper homeostasis gene discovery.

Metal Dyshomeostasis and Inflammation in Alzheimer's and Parkinson's Diseases: Possible Impact of Environmental Exposures

PubMed Central

Myhre, Oddvar; Utkilen, Hans; Duale, Nur; Brunborg, Gunnar; Hofer, Tim

2013-01-01

A dysregulated metal homeostasis is associated with both Alzheimer's (AD) and Parkinson's (PD) diseases; AD patients have decreased cortex and elevated serum copper levels along with extracellular amyloid-beta plaques containing copper, iron, and zinc. For AD, a putative hepcidin-mediated lowering of cortex copper mechanism is suggested. An age-related mild chronic inflammation and/or elevated intracellular iron can trigger hepcidin production followed by its binding to ferroportin which is the only neuronal iron exporter, thereby subjecting it to lysosomal degradation. Subsequently raised neuronal iron levels can induce translation of the ferroportin assisting and copper binding amyloid precursor protein (APP); constitutive APP transmembrane passage lowers the copper pool which is important for many enzymes. Using in silico gene expression analyses, we here show significantly decreased expression of copper-dependent enzymes in AD brain and metallothioneins were upregulated in both diseases. Although few AD exposure risk factors are known, AD-related tauopathies can result from cyanobacterial microcystin and β-methylamino-L-alanine (BMAA) intake. Several environmental exposures may represent risk factors for PD; for this disease neurodegeneration is likely to involve mitochondrial dysfunction, microglial activation, and neuroinflammation. Administration of metal chelators and anti-inflammatory agents could affect disease outcomes. PMID:23710288

Ligand-Doped Copper Oxo-hydroxide Nanoparticles are Effective Antimicrobials

NASA Astrophysics Data System (ADS)

Bastos, Carlos A. P.; Faria, Nuno; Ivask, Angela; Bondarenko, Olesja M.; Kahru, Anne; Powell, Jonathan

2018-04-01

Bacterial resistance to antimicrobial therapies is an increasing clinical problem. This is as true for topical applications as it is for systemic therapy. Topically, copper ions may be effective and cheap antimicrobials that act through multiple pathways thereby limiting opportunities to bacteria for resistance. However, the chemistry of copper does not lend itself to facile formulations that will readily release copper ions at biologically compatible pHs. Here, we have developed nanoparticulate copper hydroxide adipate tartrate (CHAT) as a cheap, safe, and readily synthesised material that should enable antimicrobial copper ion release in an infected wound environment. First, we synthesised CHAT and showed that this had disperse aquated particle sizes of 2-5 nm and a mean zeta potential of - 40 mV. Next, when diluted into bacterial medium, CHAT demonstrated similar efficacy to copper chloride against Escherichia coli and Staphylococcus aureus, with dose-dependent activity occurring mostly around 12.5-50 mg/L of copper. Indeed, at these levels, CHAT very rapidly dissolved and, as confirmed by a bacterial copper biosensor, showed identical intracellular loading to copper ions derived from copper chloride. However, when formulated at 250 mg/L in a topically applied matrix, namely hydroxyethyl cellulose, the benefit of CHAT over copper chloride was apparent. The former yielded rapid sustained release of copper within the bactericidal range, but the copper chloride, which formed insoluble precipitates at such concentration and pH, achieved a maximum release of 10 ± 7 mg/L copper by 24 h. We provide a practical formulation for topical copper-based antimicrobial therapy. Further studies, especially in vivo, are merited.

Boron-copper neutron absorbing material and method of preparation

DOEpatents

Wiencek, Thomas C.; Domagala, Robert F.; Thresh, Henry

1991-01-01

A composite, copper clad neutron absorbing material is comprised of copper powder and boron powder enriched with boron 10. The boron 10 content can reach over 30 percent by volume, permitting a very high level of neutron absorption. The copper clad product is also capable of being reduced to a thickness of 0.05 to 0.06 inches and curved to a radius of 2 to 3 inches, and can resist temperatures of 900.degree. C. A method of preparing the material includes the steps of compacting a boron-copper powder mixture and placing it in a copper cladding, restraining the clad assembly in a steel frame while it is hot rolled at 900.degree. C. with cross rolling, and removing the steel frame and further rolling the clad assembly at 650.degree. C. An additional sheet of copper can be soldered onto the clad assembly so that the finished sheet can be cold formed into curved shapes.

Circadian rhythm of blood and urinary copper in presumably healthy subjects of vegetarian food habit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, R.D.

Circadian rhythm of blood and urinary copper has been studied in presumably healthy subjects of a particular ethnic group in India who are vegetarians. A definite 24-hr variation has been observed for both blood and urinary copper. The peak for blood copper was 1500 hr and the lowest value was 0600 hr, with values of 0.185 mg/100 ml and 0.160 mg/100 ml respectively. The urinary peak and trough occurred at 0600 and 0300 hr, respectively. Remarkably higher 24-hr copper excretion values were noted (64.49 ..mu..g/day) with a range of 15-100 ..mu..g/day. The blood level of copper (0.134 mg/100 ml) remainedmore » within the range reported. One subject out of 25 deviated from the group with respect to circadian phasing and amplitude to urinary copper excretion. 20 references.« less

Stabilization of Oxidized Copper Nanoclusters in Confined Spaces

DOE PAGES

Akter, Nusnin; Wang, Mengen; Zhong, Jian-Qiang; ...

2018-01-04

Copper is an important industrial catalyst. The ability to manipulate the oxidation state of copper clusters in a controlled way is critical to understanding structure–reactivity relations of copper catalysts at the molecular level. Experimentally, cupric oxide surfaces or even small domains can only be stabilized at elevated temperatures and in the presence of oxygen, as copper can be easily reduced under reaction conditions. Herein bilayer silica films grown on a metallic substrate are used to trap diluted copper oxide clusters. By combining in situ experiments with first principles calculations, it is found that the confined space created by the silicamore » film leads to an increase in the energy barrier for Cu diffusion. Dispersed copper atoms trapped by the silica film can be easily oxidized by surface oxygen chemisorbed on the metallic substrate, which results in the formation and stabilization of Cu 2+ cations.« less

Cross-Comparison of Leaching Strains Isolated from Two Different Regions: Chambishi and Dexing Copper Mines

PubMed Central

Ngom, Baba; Liang, Yili; Liu, Xueduan

2014-01-01

A cross-comparison of six strains isolated from two different regions, Chambishi copper mine (Zambia, Africa) and Dexing copper mine (China, Asia), was conducted to study the leaching efficiency of low grade copper ores. The strains belong to the three major species often encountered in bioleaching of copper sulfide ores under mesophilic conditions: Acidithiobacillus ferrooxidans, Acidithiobacillus thiooxidans, and Leptospirillum ferriphilum. Prior to their study in bioleaching, the different strains were characterized and compared at physiological level. The results revealed that, except for copper tolerance, strains within species presented almost similar physiological traits with slight advantages of Chambishi strains. However, in terms of leaching efficiency, native strains always achieved higher cell density and greater iron and copper extraction rates than the foreign microorganisms. In addition, microbial community analysis revealed that the different mixed cultures shared almost the same profile, and At. ferrooxidans strains always outcompeted the other strains. PMID:25478575

A Systems Biology Approach to Understanding the Mechanisms of Action of an Alternative Anticancer Compound in Comparison to Cisplatin

PubMed Central

Wright, Elise P.; Padula, Matthew P.; Higgins, Vincent J.; Aldrich-Wright, Janice R.; Coorssen, Jens R.

2014-01-01

Many clinically available anticancer compounds are designed to target DNA. This commonality of action often yields overlapping cellular response mechanisms and can thus detract from drug efficacy. New compounds are required to overcome resistance mechanisms that effectively neutralise compounds like cisplatin and those with similar chemical structures. Studies have shown that 56MESS is a novel compound which, unlike cisplatin, does not covalently bind to DNA, but is more toxic to many cell lines and active against cisplatin-resistant cells. Furthermore, a transcriptional study of 56MESS in yeast has implicated iron and copper metabolism as well as the general yeast stress response following challenge with 56MESS. Beyond this, the cytotoxicity of 56MESS remains largely uncharacterised. Here, yeast was used as a model system to facilitate a systems-level comparison between 56MESS and cisplatin. Preliminary experiments indicated that higher concentrations than seen in similar studies be used. Although a DNA interaction with 56MESS had been theorized, this work indicated that an effect on protein synthesis/ degradation was also implicated in the mechanism(s) of action of this novel anticancer compound. In contrast to cisplatin, the different mechanisms of action that are indicated for 56MESS suggest that this compound could overcome cisplatin resistance either as a stand-alone treatment or a synergistic component of therapeutics. PMID:28250393

Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1.

PubMed

Juarez, Jose C; Betancourt, Oscar; Pirie-Shepherd, Steven R; Guan, Xiaojun; Price, Melissa L; Shaw, David E; Mazar, Andrew P; Doñate, Fernando

2006-08-15

A second-generation tetrathiomolybdate analogue (ATN-224; choline tetrathiomolybdate), which selectively binds copper with high affinity, is currently completing two phase I clinical trials in patients with advanced solid and advanced hematologic malignancies. However, there is very little information about the mechanism of action of ATN-224 at the molecular level. The effects of ATN-224 on endothelial and tumor cell growth were evaluated in cell culture experiments in vitro. The antiangiogenic activity of ATN-224 was investigated using the Matrigel plug model of angiogenesis. ATN-224 inhibits superoxide dismutase 1 (SOD1) in tumor and endothelial cells. The inhibition of SOD1 leads to inhibition of endothelial cell proliferation in vitro and attenuation of angiogenesis in vivo. The inhibition of SOD1 activity in endothelial cells is dose and time dependent and leads to an increase in the steady-state levels of superoxide anions, resulting in the inhibition of extracellular signal-regulated kinase phosphorylation without apparent induction of apoptosis. In contrast, the inhibition of SOD1 in tumor cells leads to the induction of apoptosis. The effects of ATN-224 on endothelial and tumor cells could be substantially reversed using Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, a catalytic small-molecule SOD mimetic. These data provide a distinct molecular target for the activity of ATN-224 and provide validation for SOD1 as a target for the inhibition of angiogenesis and tumor growth.

Incorporation of copper nanoparticles into paper for point-of-use water purification.

PubMed

Dankovich, Theresa A; Smith, James A

2014-10-15

As a cost-effective alternative to silver nanoparticles, we have investigated the use of copper nanoparticles in paper filters for point-of-use water purification. This work reports an environmentally benign method for the direct in situ preparation of copper nanoparticles (CuNPs) in paper by reducing sorbed copper ions with ascorbic acid. Copper nanoparticles were quickly formed in less than 10 min and were well distributed on the paper fiber surfaces. Paper sheets were characterized by x-ray diffraction, scanning electron microscopy, energy dispersive x-ray spectroscopy, and atomic absorption spectroscopy. Antibacterial activity of the CuNP sheets was assessed for by passing Escherichia coli bacteria suspensions through the papers. The effluent was analyzed for viable bacteria and copper release. The CuNP papers with higher copper content showed a high bacteria reduction of log 8.8 for E. coli. The paper sheets containing copper nanoparticles were effective in inactivating the test bacteria as they passed through the paper. The copper levels released in the effluent water were below the recommended limit for copper in drinking water (1 ppm). Copyright © 2014 Elsevier Ltd. All rights reserved.

Acute sensitivity of freshwater mollusks and commonly tested invertebrates to select chemicals with different toxic models of action

EPA Science Inventory

Previous studies indicate that freshwater mollusks are more sensitive than commonly tested organisms to some chemicals, such as copper and ammonia. Nevertheless, mollusks are generally under-represented in toxicity databases. Studies are needed to generate data with which to comp...

Terminal ballistics of the 9mm with Action Safety bullet or Blitz-Action-Trauma (BAT) ammunition.

PubMed

Lantz, P E; Stone, R S; Broudy, D; Morgan, T M

1994-05-01

Specialty ammunition creating atypical gunshot wounds of entrance can create confusion and may be misinterpreted by pathologists unfamiliar with the terminal ballistics of these projectiles. The previously unreported wound ballistics caused by the 9mm with Action Safety bullet described in a homicide highlights the atypical entrance wound(s) and wounding capacity of this novel ammunition. Manufactured by Geco division of Dynamit Nobel, the bullet consists of a nonjacketed solid copper alloy bullet body without a conventional lead core. The large deformation well and part of the smaller central channel is filled with a hard plastic core and post that creates a round nose bullet. The internal ballistics and unique design allow the plastic nose cap and post to separate from the copper alloy base while still in the barrel. The radiolucent nose cap leaves the bullet's path but can still penetrate tissue giving the appearance of a separate but smaller entrance wound. The sharp leading edge of the deformation well and relative high velocity of the bullet body creates a punched out entrance wound with minimal marginal abrasion. When the plastic nose cap or fragments of the plastic post impact the subject, test firings may allow an inference to the muzzle-target distance even in the absence of soot deposition or stippling.

Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme*

PubMed Central

Bonnemaison, Mathilde L.; Bäck, Nils; Duffy, Megan E.; Ralle, Martina; Mains, Richard E.; Eipper, Betty A.

2015-01-01

The adaptor protein-1 complex (AP-1), which transports cargo between the trans-Golgi network and endosomes, plays a role in the trafficking of Atp7a, a copper-transporting P-type ATPase, and peptidylglycine α-amidating monooxygenase (PAM), a copper-dependent membrane enzyme. Lack of any of the four AP-1 subunits impairs function, and patients with MEDNIK syndrome, a rare genetic disorder caused by lack of expression of the σ1A subunit, exhibit clinical and biochemical signs of impaired copper homeostasis. To explore the role of AP-1 in copper homeostasis in neuroendocrine cells, we used corticotrope tumor cells in which AP-1 function was diminished by reducing expression of its μ1A subunit. Copper levels were unchanged when AP-1 function was impaired, but cellular levels of Atp7a declined slightly. The ability of PAM to function was assessed by monitoring 18-kDa fragment-NH2 production from proopiomelanocortin. Reduced AP-1 function made 18-kDa fragment amidation more sensitive to inhibition by bathocuproine disulfonate, a cell-impermeant Cu(I) chelator. The endocytic trafficking of PAM was altered, and PAM-1 accumulated on the cell surface when AP-1 levels were reduced. Reduced AP-1 function increased the Atp7a presence in early/recycling endosomes but did not alter the ability of copper to stimulate its appearance on the plasma membrane. Co-immunoprecipitation of a small fraction of PAM and Atp7a supports the suggestion that copper can be transferred directly from Atp7a to PAM, a process that can occur only when both proteins are present in the same subcellular compartment. Altered luminal cuproenzyme function may contribute to deficits observed when the AP-1 function is compromised. PMID:26170456

Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid invivo screening method for nanotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lei Ronghui; Department of Public Health, Xi'an Jiaotong University, Xi'an 710061; Wu Chunqi

2008-10-15

Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using {sup 1}H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose ofmore » 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid {beta}-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced by nano-copper. The data generated from the current study completely supports the fact that an integrated metabolomic approach is promising for the development of a rapid invivo screening method for nanotoxicity.« less

Prediction of the critical reduced electric field strength for carbon dioxide and its mixtures with copper vapor from Boltzmann analysis for a gas temperature range of 300 K to 4000 K at 0.4 MPa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xingwen, E-mail: xwli@mail.xjtu.edu.cn; Guo, Xiaoxue; Zhao, Hu

2015-04-14

The influence of copper vapor mixed in hot CO{sub 2} on dielectric breakdown properties of gas mixture at a fixed pressure of 0.4 MPa for a temperature range of 300 K–4000 K is numerically analyzed. First, the equilibrium composition of hot CO{sub 2} with different copper fractions is calculated using a method based on mass action law. The next stage is devoted to computing the electron energy distribution functions (EEDF) by solving the two-term Boltzmann equation. The reduced ionization coefficient, the reduced attachment coefficient, and the reduced effective ionization coefficient are then obtained based on the EEDF. Finally, the critical reduced electric fieldmore » (E/N){sub cr} is obtained. The results indicate that an increasing mole fraction of copper markedly reduces (E/N){sub cr} of the CO{sub 2}–Cu gas mixtures because of copper's low ionization potential and large ionization cross section. Additionally, the generation of O{sub 2} from the thermal dissociation of CO{sub 2} contributes to the increase of (E/N){sub cr} of CO{sub 2}–Cu hot gas mixtures from about 2000 K to 3500 K.« less

The effect of copper from water and food: changes of serum nonceruloplasmin copper and brain's amyloid-beta in mice.

PubMed

Wu, Min; Han, Feifei; Gong, Weisha; Feng, Lifang; Han, Jianzhong

2016-09-14

Copper is an essential element and also produces adverse health consequences when overloaded. Food and water are the main sources of copper intake, however few studies have been conducted to investigate the difference between the ways of its intake in water and food in animals. In this study, copper was fed to mice with food as well as water (two groups: water and diet) for three months at concentrations of 6, 15 and 30 ppm. The copper concentration in water was adjusted for keeping the same amount during its intake in food. The experimental studies show a slow growth rate, lower hepatic reduced glutathione (GSH)/superoxide dismutase (SOD) activity and higher serum 'free' copper in the water group. The brain's soluble amyloid-beta 1-42 (Aβ42) of the water group was significantly higher than that of the diet group at the levels of 6 and 15 ppm. In conclusion, copper in the water group significantly increased the soluble Aβ42 in the brain and the 'free' copper in the serum, decreased the growth rate and hepatic GSH/SOD activity. The research studies carried out suggest that the copper in water is more 'toxic' than copper in diet and may increase the risk of Alzheimer's disease (AD).

Chronic copper exposure causes spatial memory impairment, selective loss of hippocampal synaptic proteins, and activation of PKR/eIF2α pathway in mice.

PubMed

Ma, Quan; Ying, Ming; Sui, Xiaojing; Zhang, Huimin; Huang, Haiyan; Yang, Linqing; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

2015-01-01

Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.

Disinfection of human enteric viruses in water by copper and silver in combination with low levels of chlorine.

PubMed Central

Abad, F X; Pintó, R M; Diez, J M; Bosch, A

1994-01-01

The efficacy of copper and silver ions, in combination with low levels of free chlorine (FC), was evaluated for the disinfection of hepatitis A virus (HAV), human rotavirus (HRV), human adenovirus, and poliovirus (PV) in water. HAV and HRV showed little inactivation in all conditions. PV showed more than a 4 log10 titer reduction in the presence of copper and silver combined with 0.5 mg of FC per liter or in the presence of 1 mg of FC per liter alone. Human adenovirus persisted longer than PV with the same treatments, although it persisted significantly less than HRV or HAV. The addition of 700 micrograms of copper and 70 micrograms of silver per liter did not enhance the inactivation rates after the exposure to 0.5 or 0.2 mg of FC per liter, although on some occasions it produced a level of inactivation similar to that induced by a higher dose of FC alone. Virus aggregates were observed in the presence of copper and silver ions, although not in the presence of FC alone. Our data indicate that the use of copper and silver ions in water systems may not provide a reliable alternative to high levels of FC for the disinfection of viral pathogens. Gene probe-based procedures were not adequate to monitor the presence of infectious HAV after disinfection. PV does not appear to be an adequate model viral strain to be used in disinfection studies. Bacteroides fragilis bacteriophages were consistently more resistant to disinfection than PV, suggesting that they would be more suitable indicators, although they survived significantly less than HAV or HRV. Images PMID:8074518

Investigating relationships between biomarkers of exposure and environmental copper and manganese levels in house dusts from a Portuguese industrial city.

PubMed

Reis, A P; Costa, S; Santos, I; Patinha, C; Noack, Y; Wragg, J; Cave, M; Sousa, A J

2015-08-01

This study reports on data obtained from a pilot survey focusing on house dust and toenail metal(loids) concentrations in residents living in the industrial city of Estarreja. The study design hereby described aims at investigating relationships between human toenails and both copper and manganese levels in settled house dusts. A total of 21 households and 30 individuals were recruited for the pilot study: 19 households corresponding to 27 residents living near the industrial complex, forming the exposed group, plus 2 households and 3 residents from residential areas with no anticipated environmental contaminants that were used for comparison. Factorial analysis was used for source identification purposes. Investigation on the potential influence of environmental factors over copper and manganese levels in the toenails was carried out via questionnaire data and multiple correspondence analysis. The results show that copper concentrations are more elevated in the indoor dusts, while manganese concentrations are more elevated in the outdoor dust samples. The geometrical relationships in the datasets suggest that the backyard soil is a probable source of manganese to the indoor dust. Copper and manganese contents in the toenail clippings are more elevated in children than in adults, but the difference between the two age groups is not statistically significant (p > 0.05). Investigation of environmental factors influencing the exposure-biomarker association indicates a probable relationship between manganese contents in indoor dust and manganese levels in toenail clippings, a result that is partially supported by the bioaccessibility estimates. However, for copper, no relationship was found between indoor dusts and the biomarkers of exposure.

Anticancer activity of silver and copper embedded chitin nanocomposites against human breast cancer (MCF-7) cells.

PubMed

Solairaj, Dhanasekaran; Rameshthangam, Palanivel; Arunachalam, Gnanapragasam

2017-12-01

Chitin is a natural biopolymer widely used in biomedical and environmental applications due to its distinctive physical, chemical and mechanical properties. Although the anticancer property of chitin nanoforms and chitin derivatives against various cancers were studied earlier, there is no report in the chitin nanostructure incorporated metal nanocomposite. The present study was aimed to investigate the cytotoxicity of chitin incorporated silver and copper nanocomposite against human breast cancer (MCF-7) cells. Cytotoxicity of chitin nanoparticles (CNP), silver nanoparticles (AgNP), copper nanoparticles (CuNP), chitin/silver nanocomposite (CNP/AgNP) and chitin/copper nanocomposite (CNP/CuNP) was evaluated. Among all the above, CNP/AgNP has shown a lower of 31 mg as inhibitory concentration (IC 50 ) value. Our study further showed the increased generation of reactive oxygen species with decreased activity of antioxidant enzymes and damage in the membrane integrity, thus confirms the cellular cytotoxic action of CNP/AgNP. In conclusion, the present study validates that, incorporating chitin nanoparticles with metallic nanostructure could be an effective and promising therapeutic agent against breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

The Scientific Illusion of Victor Burq (1822-1884).

PubMed

Walusinski, Olivier

2018-03-07

Victor Burq (1822-1884) is closely associated with a therapy named "burquism" by Jean-Martin Charcot, which was used in treating hysteria, especially hysteric anesthesia and paralysis, by applying metals, mainly copper, to affected zones. In 1876, Charcot, Luys, and Dumontpallier, commissioned by the Société de Biologie, issued 2 opinions validating the results obtained by Burq during the 25 years he dedicated to his research. From that point forward, the careers of these 3 famous physicians were lastingly reoriented toward the practice of hypnosis. This neo-mesmeric resurgence at the end of the nineteenth century can be considered the cause of an epistemological change that gave rise to "psychological medicine." During the repeated cholera epidemics in the mid-nineteenth century, Burq recommended preventive and corrective ingestion of copper, after observing that smelter workers were unaffected by the disease. The mechanisms of copper's anti-bacterial action have since been elucidated and legitimize Burq's anti-cholera campaign. Burq also advocated the ingestion of copper sulphate to treat diabetes. Current-day findings on intestinal microbiota and how these organisms influence blood sugar regulation support Burq's claims, considered far-fetched for many years. © 2018 S. Karger AG, Basel.

Background studies in support of a feasibility assessment on the use of copper-base materials for nuclear waste packages in a repository in tuff

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Konynenburg, R.A.; Kundig, K.J.A.; Lyman, W.S.

1990-06-01

This report combines six work units performed in FY`85--86 by the Copper Development Association and the International Copper Research Association under contract with the University of California. The work includes literature surveys and state-of-the-art summaries on several considerations influencing the feasibility of the use of copper-base materials for fabricating high-level nuclear waste packages for the proposed repository in tuff rock at Yucca Mountain, Nevada. The general conclusion from this work was that copper-base materials are viable candidates for inclusion in the materials selection process for this application. 55 refs., 48 figs., 22 tabs.

A preliminary study of preservative retention and penetration in ACQ-treated timbers using near infrared spectroscopy

Treesearch

Chi-Leung So; Thomas L. Eberhardt; Stan T. Lebow; Leslie H. Groom

2006-01-01

Near infrared (NIR) spectroscopy has been previously used in our laboratory to predict copper, chromium, and arsenic levels in samples of chromated copper arsenate (CCA)-treated wood. In the present study, we utilized our custom-made NIR scanning system, NIRVANA (near infrared visual and automated numerical analysis), to scan cross sections of ACQ (alkaline copper quat...

Copper Deficiency in Calves in Northcentral Manitoba

PubMed Central

Smart, M. E.; Gudmundson, J.; Brockman, R. P.; Cymbaluk, N.; Doige, C.

1980-01-01

Four seven month old Simmental calves were examined because of unthriftiness, a persistent cough, stiffness and lameness. The calves had gastrointestinal and pulmonary parasitism. Analysis of the blood copper levels of these calves and of cows and calves on the farm indicated a generalized deficiency. Only the calves affected with parasitism showed signs of clinical copper deficiency. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:7260830

Trace copper measurements and electrical effects in LPE HgCdTe

NASA Astrophysics Data System (ADS)

Tower, J. P.; Tobin, S. P.; Norton, P. W.; Bollong, A. B.; Socha, A.; Tregilgas, J. H.; Ard, C. K.; Arlinghaus, H. F.

1996-08-01

Recent improvements in sputter initiated resonance ionization spectroscopy (SIRIS) have now made it possible to measure copper in HgCdTe films into the low 1013 cm-3 range. We have used this technique to show that copper is responsible for type conversion in n-type HgCdTe films. Good n-type LPE films were found to have less than 1 x 1014 cm-3 copper, while converted p-type samples were found to have copper concentrations approximately equal to the hole concentrations. Some compensated n-type samples with low mobilities have copper concentrations too low to account for the amount of compensation and the presence of a deep acceptor level is suggested. In order to study diffusion of copper from substrates into LPE layers, a CdTe boule was grown intentionally spiked with copper at approximately 3 x 1016 cm-3. Annealing HgCdTe films at 360°C was found to greatly increase the amount of copper that diffuses out of the substrates and a substrate screening technique was developed based on this phenomenon. SIRIS depth profiles showed much greater copper in HgCdTe films than in the substrates, indicating that copper is preferentially attracted to HgCdTe over Cd(Zn)Te. SIRIS spatial mapping showed that copper is concentrated in substrate tellurium inclusions 5 25 times greater than in the surrounding CdZnTe matrix.

Impact of ionophore monensin on performance and Cu uptake in earthworm Eisenia andrei exposed to copper-contaminated soil.

PubMed

Zidar, Primož; Kos, Monika; Vogel-Mikuš, Katarina; van Elteren, Johannes Teun; Debeljak, Marta; Žižek, Suzana

2016-10-01

Exposure of beneficial soil organisms to chemical mixtures is of great concern and can result in unexpected deleterious consequences. We investigated the effects of concurrent soil contamination with monensin, a veterinary pharmaceutical and feed additive, and copper, on earthworm copper uptake and reproductive success. The animals were exposed for 14 or 28 days to both substances and the results showed that the Cu body burden of earthworms increases in the presence of monensin. The harmful effects of Cu on earthworm cocoon production were considerably higher when monensin was also present in the soil. To localise the copper in earthworm tissues, histological staining was performed using two different dyes (rubeanic acid and 5-4-(p-dimethylaminobenzylidene)-rhodanine). Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to quantify the Cu levels in the tissues. Cu was found predominantly in the gut wall. The Cu content in the body wall was at least ten times lower compared to the gut, but was proportional to the level of soil contamination. Concurrent soil contamination with monensin and copper resulted in higher earthworm Cu levels and in decreased reproductive success of these important soil decomposers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using XAS and SXRF to Study Copper in Wilson Disease at the Molecular and Tissue Level

NASA Astrophysics Data System (ADS)

Ralle, Martina; Blackburn, Ninian J.; Lutsenko, Svetlana

2007-02-01

Wilson disease (WD) is a genetic disorder of copper metabolism associated with severe hepatic, neurological, and psychiatric abnormalities. In WD, the billiary copper excretion is impaired and copper accumulates in tissues, particularly in the liver and the brain. The affected gene, ATP7B, encodes the copper transporting ATPase, Wilson disease protein (WNDP). WNDP has six copper binding sites in the N-terminal portion of the molecule. Each site includes the conserved amino acid sequence MXCXXC, and binds 1 Cu(I) through its 2 cysteine residues. We performed X-ray absorption studies at the Cu Kα-edge on the recombinant N-terminal domain of WNDP (N-WNDP). Copper was bound to N-WNDP either in vivo or in vitro in the presence of different reducing agents. We found that in N-WNDP copper is predominantly coordinated in a linear fashion by two cysteines, with the appearance of a Cu-Cu interaction when all metal binding sites are filled. Increasing amounts of reducing agents containing sulfide or phosphine groups led to binding of the exogenous ligands to copper thereby increasing the coordination number of copper from two to three. To better understand the role of copper in WD, we utilized livers of the 6-weeks-old Atp7b-/- mice (an animal model for WD) in which the copper concentration was 10-20-fold higher compared to that of the control mice. The distribution of copper in hepatocytes was evaluated by synchrotron based X-ray fluorescence microprobe (SXRF). We demonstrate that we can prepare liver slices that retain copper and can detect copper with subcellular resolution. On the same sections μ-XANES (spot size: 5 micron) was used to determine the oxidation state of copper.

Genetic Dissection of Nutritional Copper Signaling in Chlamydomonas Distinguishes Regulatory and Target Genes

PubMed Central

Eriksson, Mats; Moseley, Jeffrey L.; Tottey, Stephen; del Campo, Jose A.; Quinn, Jeanette; Kim, Youngbae; Merchant, Sabeeha

2004-01-01

A genetic screen for Chlamydomonas reinhardtii mutants with copper-dependent growth or nonphotosynthetic phenotypes revealed three loci, COPPER RESPONSE REGULATOR 1 (CRR1), COPPER RESPONSE DEFECT 1 (CRD1), and COPPER RESPONSE DEFECT 2 (CRD2), distinguished as regulatory or target genes on the basis of phenotype. CRR1 was shown previously to be required for transcriptional activation of target genes like CYC6, CPX1, and CRD1, encoding, respectively, cytochrome c6 (which is a heme-containing substitute for copper-containing plastocyanin), coproporphyrinogen III oxidase, and Mg-protoporphyrin IX monomethylester cyclase. We show here that CRR1 is required also for normal accumulation of copper proteins like plastocyanin and ferroxidase in copper-replete medium and for apoplastocyanin degradation in copper-deficient medium, indicating that a single pathway controls nutritional copper homeostasis at multiple levels. CRR1 is linked to the SUPPRESSOR OF PCY1-AC208 13 (SOP13) locus, which corresponds to a gain-of-function mutation resulting in copper-independent expression of CYC6. CRR1 is required also for hypoxic growth, pointing to a physiologically meaningful regulatory connection between copper deficiency and hypoxia. The growth phenotype of crr1 strains results primarily from secondary iron deficiency owing to reduced ferroxidase abundance, suggesting a role for CRR1 in copper distribution to a multicopper ferroxidase involved in iron assimilation. Mutations at the CRD2 locus also result in copper-conditional iron deficiency, which is consistent with a function for CRD2 in a pathway for copper delivery to the ferroxidase. Taken together, the observations argue for a specialized copper-deficiency adaptation for iron uptake in Chlamydomonas. PMID:15514054

Evolution of a Heavy Metal Homeostasis/Resistance Island Reflects Increasing Copper Stress in Enterobacteria

PubMed Central

Staehlin, Benjamin M.; Gibbons, John G.; Rokas, Antonis; O’Halloran, Thomas V.; Slot, Jason C.

2016-01-01

Copper homeostasis in bacteria is challenged by periodic elevation of copper levels in the environment, arising from both natural sources and human inputs. Several mechanisms have evolved to efflux copper from bacterial cells, including the cus (copper sensing copper efflux system), and pco (plasmid-borne copper resistance system) systems. The genes belonging to these two systems can be physically clustered in a Copper Homeostasis and Silver Resistance Island (CHASRI) on both plasmids and chromosomes in Enterobacteria. Increasing use of copper in agricultural and industrial applications raises questions about the role of human activity in the evolution of novel copper resistance mechanisms. Here we present evidence that CHASRI emerged and diversified in response to copper deposition across aerobic and anaerobic environments. An analysis of diversification rates and a molecular clock model suggest that CHASRI experienced repeated episodes of elevated diversification that could correspond to peaks in human copper production. Phylogenetic analyses suggest that CHASRI originated in a relative of Enterobacter cloacae as the ultimate product of sequential assembly of several pre-existing two-gene modules. Once assembled, CHASRI dispersed via horizontal gene transfer within Enterobacteriaceae and also to certain members of Shewanellaceae, where the original pco module was replaced by a divergent pco homolog. Analyses of copper stress mitigation suggest that CHASRI confers increased resistance aerobically, anaerobically, and during shifts between aerobic and anaerobic environments, which could explain its persistence in facultative anaerobes and emergent enteric pathogens. PMID:26893455

Correlation of Zn2+ content with aflatoxin content of corn.

PubMed Central

Failla, L J; Lynn, D; Niehaus, W G

1986-01-01

Forty-nine samples from the 1983 Virginia corn harvest were analyzed for aflatoxin, zinc, copper, iron, and manganese content. Values (mean +/- standard deviation) were as follows: aflatoxin, 117 +/- 360 micrograms/kg; zinc, 22.5 +/- 3.4 mg/kg; copper, 2.27 +/- 0.56 mg/kg; iron, 40.8 +/- 18.7 mg/kg; and manganese, 5.1 +/- 1.1 mg/kg. Aflatoxin levels positively correlated with zinc (Spearman correlation coefficient, 0.385; P less than 0.006) and copper levels (Spearman correlation coefficient, 0.573; P less than 0.0001). Based on biochemical data in the literature, we believe that the correlation with zinc is important and that there may be a cause-and-effect relationship between zinc levels in corn and aflatoxin levels which are produced upon infection with Aspergillus flavus or A. parasiticus. Control of aflatoxin contamination in field corn by decreasing the zinc levels may be feasible, but no methods to decrease zinc levels are currently available. PMID:3729406

Low-level copper exposures increase visibility and vulnerability of juvenile coho salmon to cutthroat trout predators

USGS Publications Warehouse

McIntyre, Jenifer K.; Baldwin, David H.; Beauchamp, David A.; Scholz, Nathaniel L.

2012-01-01

Copper contamination in surface waters is common in watersheds with mining activities or agricultural, industrial, commercial, and residential human land uses. This widespread pollutant is neurotoxic to the chemosensory systems of fish and other aquatic species. Among Pacific salmonids (), copper-induced olfactory impairment has previously been shown to disrupt behaviors reliant on a functioning sense of smell. For juvenile coho salmon (O. kisutch), this includes predator avoidance behaviors triggered by a chemical alarm cue (conspecific skin extract). However, the survival consequences of this sublethal neurobehavioral toxicity have not been explored. In the present study juvenile coho were exposed to low levels of dissolved copper (5–20 μg/L for 3 h) and then presented with cues signaling the proximity of a predator. Unexposed coho showed a sharp reduction in swimming activity in response to both conspecific skin extract and the upstream presence of a cutthroat trout predator (O. clarki clarki) previously fed juvenile coho. This alarm response was absent in prey fish that were exposed to copper. Moreover, cutthroat trout were more effective predators on copper-exposed coho during predation trials, as measured by attack latency, survival time, and capture success rate. The shift in predator–prey dynamics was similar when predators and prey were co-exposed to copper. Overall, we show that copper-exposed coho are unresponsive to their chemosensory environment, unprepared to evade nearby predators, and significantly less likely to survive an attack sequence. Our findings contribute to a growing understanding of how common environmental contaminants alter the chemical ecology of aquatic communities.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akter, Nusnin; Wang, Mengen; Zhong, Jian-Qiang

Copper is an important industrial catalyst. The ability to manipulate the oxidation state of copper clusters in a controlled way is critical to understanding structure–reactivity relations of copper catalysts at the molecular level. Experimentally, cupric oxide surfaces or even small domains can only be stabilized at elevated temperatures and in the presence of oxygen, as copper can be easily reduced under reaction conditions. Herein bilayer silica films grown on a metallic substrate are used to trap diluted copper oxide clusters. By combining in situ experiments with first principles calculations, it is found that the confined space created by the silicamore » film leads to an increase in the energy barrier for Cu diffusion. Dispersed copper atoms trapped by the silica film can be easily oxidized by surface oxygen chemisorbed on the metallic substrate, which results in the formation and stabilization of Cu 2+ cations.« less

The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit

PubMed Central

Alissa, Eman M; Bahijri, Suhad M; Lamb, David J; Ferns, Gordon A A

2004-01-01

It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25–1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination. PMID:15379959

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cullen, W.R.; McBride, B.C.; Pickett, A.W.

The wood preservative chromated copper arsenate (CCA) is a very widely used product. As it contains both copper and arsenic, it is not dissimilar to the pigments Scheele's green and Schweinfurter's green which were found to be biologically convertible to the toxic Gosio gas (B. Gosio, Ber. 30:1024-1026, 1897) later identified by Challenger and co-workers as trimethylarsine (F. Challenger, Adv. Enzymol. 12:429-491, 1951). Thus, it was of interest to determine whether microbiological action on CCA and wood treated with CCA could result in the production of trimethylarsine. The authors report that the fungus Candida humicola will produce this arsine frommore » dilute solutions of CCA and from wood soaked in CCA. 12 references.« less

Polyoxometalates as antitumor agents: Bioactivity of a new polyoxometalate with copper on a human osteosarcoma model.

PubMed

León, I E; Porro, V; Astrada, S; Egusquiza, M G; Cabello, C I; Bollati-Fogolin, M; Etcheverry, S B

2014-10-05

Polyoxometalates (POMs) are early transition metal oxygen anion clusters. They display interesting biological effects mainly related to their antiviral and antitumor properties. On the other hand, copper compounds also show different biological and pharmacological effects in cell culture and in animal models. We report herein for the first time, a detailed study of the mechanisms of action of a copper(II) compound of the group of HPOMs with the formula K7Na3[Cu4(H2O)2(PW9034)2]20H2O (PW9Cu), in a model of human osteosarcoma derived cell line, MG-63. The compound inhibited selectively the viability of the osteosarcoma cells in the range of 25-100μM (p<0.01). Besides, we have clearly shown a more deleterious action of PW9Cu on tumor osteoblasts than in normal cells. Cytotoxicity studies also showed deleterious effects for PW9Cu. The increment of reactive oxygen species (ROS) and the decrease of the GSH/GSSG ratio were involved in the antiproliferative effects of PW9Cu. Moreover, the compound caused cell cycle arrest in G2 phase, triggering apoptosis as determined by flow cytometry. As a whole, these results showed the main mechanisms of the deleterious effects of PW9Cu in the osteosarcoma cell line MG-63, demonstrating that this compound is a promissory agent for cancer treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

From BACE1 Inhibitor to Multifunctionality of Tryptoline and Tryptamine Triazole Derivatives for Alzheimer’s Disease

PubMed Central

Jiaranaikulwanitch, Jutamas; Govitrapong, Piyarat; Fokin, Valery V.; Vajragupta, Opa

2013-01-01

Efforts to discover new drugs for Alzheimer’s disease emphasizing multiple targets was conducted seeking to inhibit amyloid oligomer formation and to prevent radical formation. The tryptoline and tryptamine cores of BACE1 inhibitors previously identified by virtual screening were modified in silico for additional modes of action. These core structures were readily linked to different side chains using 1,2,3-triazole rings as bridges by copper catalyzed azide-alkyne cycloaddition reactions. Three compounds among the sixteen designed compounds exerted multifunctional activities including β-secretase inhibitory action, anti-amyloid aggregation, metal chelating and antioxidant effects at micromolar levels. The neuroprotective effects of the multifunctional compounds 6h, 12c and 12h on Aβ1–42 induced neuronal cell death at 1 μM were significantly greater than those of the potent single target compound, BACE1 inhibitor IV and were comparable to curcumin. The observed synergistic effect resulting from the reduction of the Aβ1–42 neurotoxicity cascade substantiates the validity of our multifunctional strategy in drug discovery for Alzheimer’s disease. PMID:22781443

Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators.

PubMed

Genc, Gizem Esra; Ozturk, Zeynep; Gumuslu, Saadet; Kupesiz, Alphan

2016-03-01

The goal of the present study was to determine the levels of minerals in chronically transfused thalassaemic patients living in Antalya, Turkey and to determine mineral levels in groups using different iron chelators. Three iron chelators deferoxamine, deferiprone and deferasirox have been used to remove iron from patients' tissues. There were contradictory results in the literature about minerals including selenium, zinc, copper, and magnesium in thalassaemia major patients. Blood samples from the 60 thalassaemia major patients (the deferoxamine group, n = 19; the deferiprone group, n = 20 and the deferasirox group, n = 21) and the controls (n = 20) were collected. Levels of selenium, zinc, copper, magnesium, and iron were measured, and all of them except iron showed no significant difference between the controls and the patients regardless of chelator type. Serum copper levels in the deferasirox group were lower than those in the control and deferoxamine groups, and serum magnesium levels in the deferasirox group were higher than those in the control, deferoxamine and deferiprone groups. Iron levels in the patient groups were higher than those in the control group, and iron levels showed a significant correlation with selenium and magnesium levels. Different values of minerals in thalassaemia major patients may be the result of different dietary intake, chelator type, or regional differences in where patients live. That is why minerals may be measured in thalassaemia major patients at intervals, and deficient minerals should be replaced. Being careful about levels of copper and magnesium in thalassaemia major patients using deferasirox seems to be beneficial.

Glutamate-Mediated Primary Somatosensory Cortex Excitability Correlated with Circulating Copper and Ceruloplasmin

PubMed Central

Tecchio, Franca; Assenza, Giovanni; Zappasodi, Filippo; Mariani, Stefania; Salustri, Carlo; Squitti, Rosanna

2011-01-01

Objective. To verify whether markers of metal homeostasis are related to a magnetoencephalographic index representative of glutamate-mediated excitability of the primary somatosensory cortex. The index is identified as the source strength of the earliest component (M20) of the somatosensory magnetic fields (SEFs) evoked by right median nerve stimulation at wrist. Method. Thirty healthy right-handed subjects (51 ± 22 years) were enrolled in the study. A source reconstruction algorithm was applied to assess the amount of synchronously activated neurons subtending the M20 and the following SEF component (M30), which is generated by two independent contributions of gabaergic and glutamatergic transmission. Serum copper, ceruloplasmin, iron, transferrin, transferrin saturation, and zinc levels were measured. Results. Total copper and ceruloplasmin negatively correlated with the M20 source strength. Conclusion. This pilot study suggests that higher level of body copper reserve, as marked by ceruloplasmin variations, parallels lower cortical glutamatergic responsiveness. PMID:22145081

The evaluation of zinc and copper content in tooth enamel without any pathological changes - an in vitro study.

PubMed

Klimuszko, Elzbieta; Orywal, Karolina; Sierpinska, Teresa; Sidun, Jarosław; Golebiewska, Maria

2018-01-01

The objectives of the study were to evaluate the content of copper and zinc in individual layers of tooth enamel and to analyze the relationships between the study minerals in individual layers of tooth enamel. Fifteen human permanent teeth were cut off every 150 μm alongside the labial surface. Acid biopsy of each layer was performed. The zinc content was determined using the air-acetylene flame method. The copper content was determined using the electrothermal technique with argon. The mean zinc concentrations increased significantly starting from the outer enamel surface, with the maximum concentration in the 150-300 μm layer. The mean copper concentrations increased substantially from the outer enamel surface to a depth of 150 μm, and then a slight downward trend of this mineral levels was seen, down to a depth of 450 μm. Strong positive correlation was found between the zinc and copper concentrations at depths of 150-300, 450-600 and 600-750 μm. The levels of zinc and copper in the outer enamel layers may have an effect on the increased content of unipolar minerals at deeper enamel layers. The content of the study elements determined may reflect the process of mineralization and maturation of enamel in the pre-eruption period.

[MORPHOFUNCTIONAL ADJUSTMENT VASCULAR AND CELLULAR COMPONENTS OF THE CEREBELLAR CORTEX IN EXPOSURE TO BODY SULFATES OF COPPER, ZINC AND IRON].

PubMed

Grintsova, N; Vasko, L; Kiptenko, L; Gortinsky, A; Murenets, N

2015-09-01

In order to analyze the morphological and morphometric reconstructions of the vascular bed, and Purkinje cells of the cerebellar cortex of rats in long-term action (for 90 days) on the body of sulphates of copper, zinc and iron, an experiment was conducted on 48 adult white male rats weighing 200-250 g in age 5-7 months. We used anatomical, morphometric, statistical and common methods of microanatomical research. It was found that the combined effect on the body of sulphates of copper and zinc, and iron in the cerebellum has enough expressive toxicity, which affects the condition of the vascular bed, and Purkinje cells. The degree of morphological transformations is in direct proportion to the duration of the experiment. In the pathogenesis of violations leading role played by hypoxia, develop signs of swelling of the cerebellar cortex with signs hemorrhagic infiltration, the severity of which is maximum on the 60th day of the experiment.

Repetitive switching for an electromagnetic rail gun

NASA Astrophysics Data System (ADS)

Gruden, J. M.

1983-12-01

Previous testing on a repetitive opening switch for inductive energy storage has proved the feasibility of the rotary switch concept. The concept consists of a rotating copper disk (rotor) with a pie-shaped insulator section and brushes which slide along each of the rotor surfaces. While on top of the copper surface, the brushes and rotor conduct current allowing the energy storage inductor to charge. When the brushes slide onto the insulator section, the current cannot pass through the rotor and is diverted into the load. This study investigates two new brush designs and a rotor modification designed to improve the current commutating capabilities of the switch. One brush design (fringe fiber) employs carbon fibers on the leading and trailing edge of the brush to increase the resistive commutating action as the switch opens and closes. The other brush design uses fingers to conduct current to the rotor surface, effectively increasing the number of brush contact points. The rotor modification was the placement of tungsten inserts at the copper-insulator interfaces.

Characterization of the binding of 2-mercaptobenzimidazole to bovine serum albumin.

PubMed

Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

2015-04-01

2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment is potentially harmful to human health. In this article, the interaction of MBI with bovine serum albumin (BSA) was explored using spectroscopic and molecular docking methods under physiological conditions. The positively charged MBI can spontaneously bind with the negatively charged BSA through electrostatic forces with one binding site. The site marker competition experiments and the molecular docking study revealed that MBI bound into site II (subdomain IIIA) of BSA, which further led to some secondary structure and microenvironmental changes of BSA. This work provides useful information on understanding the toxicological actions of MBI at the molecular level. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of low-stiffness closeout overwrap on rocket thrust-chamber life

NASA Technical Reports Server (NTRS)

Kasper, H. J.; Nota-Donato, J. J.

1979-01-01

Three rocket thrust chambers with copper liners and a thrust level of 20.9 kN were cyclically test fired to failure. Two of the liners were made from oxygen free, high conductivity (OFHC) copper and from annealed Amzirc. The milled coolant channels were closed out with a thin copper closeout over which a fiberglass composite was wrapped to provide hoop strength only. Experimental data are presented, along with the results of a preliminary analysis that was performed before fabrication to evaluate the life extending potential of a thin copper closeout with a fiberglass overwrap.

Streptococcus mutans copper chaperone, CopZ, is critical for biofilm formation and competitiveness.

PubMed

Garcia, S S; Du, Q; Wu, H

2016-12-01

The oral cavity is a dynamic environment characterized by hundreds of bacterial species, saliva, and an influx of nutrients and metal ions such as copper. Although there is a physiologic level of copper in the saliva, the oral cavity is often challenged with an influx of copper ions. At high concentrations copper is toxic and must therefore be strictly regulated by pathogens for them to persist and cause disease. The cariogenic pathogen Streptococcus mutans manages excess copper using the copYAZ operon that encodes a negative DNA-binding repressor (CopY), the P1-ATPase copper exporter (CopA), and the copper chaperone (CopZ). These hypothetical roles of the copYAZ operon in regulation and copper transport to receptors led us to investigate their contribution to S. mutans virulence. Mutants defective in the copper chaperone CopZ, but not CopY or CopA, were impaired in biofilm formation and competitiveness against commensal streptococci. Characterization of the CopZ mutant biofilm revealed a decreased secretion of glucosyltransferases and reduced expression of mutacin genes. These data suggest that the function of copZ on biofilm and competitiveness is independent of copper resistance and CopZ is a global regulator for biofilm and other virulence factors. Further characterization of CopZ may lead to the identification of new biofilm pathways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of copper ions on the characteristics of egg white gel induced by strong alkali.

PubMed

Shao, Yaoyao; Zhao, Yan; Xu, Mingsheng; Chen, Zhangyi; Wang, Shuzhen; Tu, Yonggang

2017-09-01

This study investigated the effects of copper ions on egg white (EW) gel induced by strong alkali. Changes in gel characteristics were examined through texture profile analysis, scanning electron microscopy (SEM), and chemical methods. The value of gel strength reached its maximum when 0.1% copper ions was added. However, the lowest cohesiveness values were observed at 0.1%. The springiness of gel without copper ions was significantly greater than the gel with copper ions added. SEM results illustrated that the low concentration of copper ions contributes to a dense and uniform gel network, and an open matrix was formed at 0.4%. The free and total sulphhydryl group content in the egg white protein gel significantly decreased with the increased copper. The increase of copper ions left the contents of ionic and hydrogen bonds basically unchanged, hydrophobic interaction presented an increasing trend, and the disulfide bond exhibited a completely opposite change. The change of surface hydrophobicity proved that the main binding force of copper induced gel was hydrophobic interaction. However, copper ions had no effect on the protein component of the gels. Generally, a low level of copper ions facilitates protein-protein association, which is involved in the characteristics of gels. Instead, high ionic strength had a negative effect on gels induced by strong alkali. © 2017 Poultry Science Association Inc.

Design solutions for the solar cell interconnect fatigue fracture problem

NASA Technical Reports Server (NTRS)

Mon, G. R.; Ross, R. G., Jr.

1982-01-01

Mechanical fatigue of solar cell interconnects is a major failure mechanism in photovoltaic arrays. A comprehensive approach to the reliability design of interconnects, together with extensive design data for the fatigue properties of copper interconnects, has been published. This paper extends the previous work, developing failure prediction (fatigue) data for additional interconnect material choices, including aluminum and a variety of copper-Invar and copper-steel claddings. An improved global fatigue function is used to model the probability-of-failure statistics of each material as a function of level and number of cycles of applied strain. Life-cycle economic analyses are used to evaluate the relative merits of each material choce. The copper-Invar clad composites demonstrate superior performance over pure copper. Aluminum results are disappointing.

Chelation and effectiveness of salicylate related compounds on pyresis, sedimentation rate and hematocrit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schubert, J.; Rosenthal, M.W.; Fried, J.F.

1984-01-01

The mechanism of action and identification of sites of salicylates and related compounds in antipyresis were studied. Structure-activity investigations of antipyresis were made using Sprague-Dawley rats. Results showed copper was chelated by the salicylate, passes through the cell membrane, and repairs the lesion. 13 references, 2 figures. (ACR)

75 FR 63177 - Notice of a Public Meeting: Stakeholder Meeting Concerning EPA's Long-Term Revisions to the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-14

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9213-1] Notice of a Public Meeting: Stakeholder Meeting...: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The U.S. Environmental Protection Agency (EPA... Copper Rule (LCR). EPA is holding a stakeholder meeting to provide information to the public and an...

THE RÔLE OF CERTAIN METALLIC IONS AS OXIDATION CATALYSTS

PubMed Central

Cook, S. F.

1926-01-01

1. When iron and copper are allowed to act on hydrogen peroxide and pyrogallol, enough carbon dioxide is produced to be readily measured. 2. The curve of the production of carbon dioxide may be fitted by an empirical equation, by the use of which the initial rate and the total amount of the oxidation may be determined. 3. The effect of the concentration of the reagents is different in each case, the effect varying as a fractional power of the copper and pyrogallol concentrations and as a logarithmic function of the hydrogen peroxide concentration. 4. When gold or silver is used the rate changes suddenly during the course of the reaction due to the precipitation of colloidal metal. 5. Mercury, cadmium, zinc, tin, and some other metals have no effect. 6. A theoretical set of equations is assumed to account for the action of the metals. 7. The metals are assumed to act by means of the formation of intermediate peroxides. 8. Experiments on the action of gold indicate that the metals are active in the ionic and not in the colloidal state. PMID:19872322

Estimation of CO2-Equivalent Emission under the Copper Fire Refining Process

NASA Astrophysics Data System (ADS)

Chesnokov, Yu N.; Lisienko, V. G.; Holod, S. I.; Anufriev, V. P.; Lapteva, A. V.

2017-06-01

Non-ferrous metallurgy is one of the most energy-consuming and carbon-emissive sectors of industry. This is due to the fact that the volume of greenhouse gas (GHG) emissions is stipulated by energy consumption. Uralelectromed is a city-forming enterprise of the Verkhnyaya Pyshma. The situation is similar other cities of the old industrial regions of the Russian Federation (Krasnouralsk, Verkhnaya Salda, Karabash, etc.) Verkhnyaya Pyshma has many characteristics of “a clever city”. It can be compared to Hamburg where blister copper is being produced at the center of the city at a copper smelting plant Aurubis. Following the example of such ecologically clean country as Germany and in order to assess how modern energy-efficient low-carbon technologies can provide a favorable habitat, and an acceptable level of carbon footprint, the authors estimated the level of greenhouse gas, i.e., carbon dioxide emission produced by the Uralelectromed. The emission of greenhouse gas -carbon dioxide in the process of fire refining of blister copper has been calculated. The anode melting process consists of several stages where the most important ones are melting of charge, oxidation, and copper melt reduction. Calculations are based on taking into account the mass of burnt carbon of natural gas and the thermal dissociation of fuel oil. It implies that a complete combustion of carbon takes place. The specific value of carbon dioxide emission of the copper refining process is averaged 181 kg CO2 per 1 ton of anode copper.

Copper Resistance of the Emerging Pathogen Acinetobacter baumannii

PubMed Central

Williams, Caitlin L.; Neu, Heather M.; Gilbreath, Jeremy J.; Michel, Sarah L. J.; Zurawski, Daniel V.

2016-01-01

ABSTRACT Acinetobacter baumannii is an important emerging pathogen that is capable of causing many types of severe infection, especially in immunocompromised hosts. Since A. baumannii can rapidly acquire antibiotic resistance genes, many infections are on the verge of being untreatable, and novel therapies are desperately needed. To investigate the potential utility of copper-based antibacterial strategies against Acinetobacter infections, we characterized copper resistance in a panel of recent clinical A. baumannii isolates. Exposure to increasing concentrations of copper in liquid culture and on solid surfaces resulted in dose-dependent and strain-dependent effects; levels of copper resistance varied broadly across isolates, possibly resulting from identified genotypic variation among strains. Examination of the growth-phase-dependent effect of copper on A. baumannii revealed that resistance to copper increased dramatically in stationary phase. Moreover, A. baumannii biofilms were more resistant to copper than planktonic cells but were still susceptible to copper toxicity. Exposure of bacteria to subinhibitory concentrations of copper allowed them to better adapt to and grow in high concentrations of copper; this copper tolerance response is likely achieved via increased expression of copper resistance mechanisms. Indeed, genomic analysis revealed numerous putative copper resistance proteins that share amino acid homology to known proteins in Escherichia coli and Pseudomonas aeruginosa. Transcriptional analysis revealed significant upregulation of these putative copper resistance genes following brief copper exposure. Future characterization of copper resistance mechanisms may aid in the search for novel antibiotics against Acinetobacter and other highly antibiotic-resistant pathogens. IMPORTANCE Acinetobacter baumannii causes many types of severe nosocomial infections; unfortunately, some isolates have acquired resistance to almost every available antibiotic, and treatment options are incredibly limited. Copper is an essential nutrient but becomes toxic at high concentrations. The inherent antimicrobial properties of copper give it potential for use in novel therapeutics against drug-resistant pathogens. We show that A. baumannii clinical isolates are sensitive to copper in vitro, both in liquid and on solid metal surfaces. Since bacterial resistance to copper is mediated though mechanisms of efflux and detoxification, we identified genes encoding putative copper-related proteins in A. baumannii and showed that expression of some of these genes is regulated by the copper concentration. We propose that the antimicrobial effects of copper may be beneficial in the development of future therapeutics that target multidrug-resistant bacteria. PMID:27520808

Copper stimulation of LHRH release from median eminence explants. III. A process dependent on extracellular sodium.

PubMed

Colombani-Vidal, M; Barnea, A

1986-01-01

Copper, complexed to histidine (CuHis), stimulates LHRH release from explants of the median eminence area (MEA). To gain further understanding of the mechanism of copper action, in this study, we assessed the Na+ and energy requirements for CuHis stimulation of LHRH release. MEA explants, obtained from adult male rats, were incubated at 37 degrees C for 15 min with 100 microM CuHis and then for 45 min in CuHis-free medium (Krebs-Ringer-phosphate buffer, pH 7.4). LHRH released into the medium was evaluated by RIA. When the incubation buffer contained 143 mM Na+, CuHis stimulated the release of LHRH from a basal level of 17.2 +/- 1.26 (mean +/- SEM, n = 7) to 74.5 +/- 6.2 pg/60 min per MEA. When [Na+] was reduced to 16 mM Na+ (by substituting with Li+), CuHis-stimulated LHRH release was inhibited by 80% (p less than 0.001); indicating a requirement for Na+. In addition, we found that CuHis-stimulated LHRH release was a saturable function of Na+ concentration; saturation achieved with about 100 mM Na+. To assess the requirement for Na+ transport, we evaluated the effect of 1 mM ouabain, 10 microM tetrodotoxin (TTX), or 100 microM amiloride on CuHis stimulation of LHRH release. Ouabain inhibited CuHis stimulation of LHRH release by 80%, whereas TTX and amiloride were ineffective. In addition, we observed that CuHis did not stimulate LHRH release when incubation was carried out at 4 degrees C or at 37 degrees C in the presence of 5 mM KCN.(ABSTRACT TRUNCATED AT 250 WORDS)

[Serum immunoglobulin levels in women fitted with a copper T intrauterine contraceptive device (author's transl)].

PubMed

Tatra, G; Beck, A; Prunner, Ch; Breitenecker, G

1975-10-31

Serum concentrations of the immunoglobulins IgG, IgM and IgA were assayed by single radial immunodiffusion in 37 women before insertion of Copper T IUD and 6 to 12 months subsequently. There was a tendency towards an increase in immuno-globulin levels with the IUD in situ, but the results were not of statistical significance.

Four trace elements in pregnant women and their relationships with adverse pregnancy outcomes.

PubMed

Shen, P-J; Gong, B; Xu, F-Y; Luo, Y

2015-12-01

Lack of trace elements during pregnancy is detrimental to maternal and fetal health. Our aim is to study the changes in trace element levels in Chinese pregnant women and their association with adverse pregnancy outcomes. 1568 cases of Chinese pregnant women in remote areas were collected for a prospective cohort study. Serum copper, zinc, calcium and iron levels were measured at pre-pregnancy, 1st trimester (7w-12w), 2nd trimester (24w-28w) and 3rd trimester (35w-40w). (1) Serum copper levels was significantly higher after pregnancy than before, calcium and iron levels decreased, but zinc levels did not change significantly. (2) Copper and zinc deficiency in pregnant women was not a common finding, but lack of iron and calcium was frequently encountered; iron deficiency was especially common in the 3rd trimester (42.27%). (3) Serum zinc and iron levels in patients who either had a miscarriage or a preterm delivery were significantly lower than in the control group (p < 0.05). In patients with premature rupture of membranes, serum zinc levels were significantly lower (p < 0.05). In patients with intrauterine growth restriction (IUGR), serum copper, zinc, calcium and iron were significantly lower (p < 0.05). Trace elements is closely associated with fetal growth and development during pregnancy. Deficiency can lead to adverse pregnancy outcomes. Therefore, we should have a reasonable diet, replenish trace elements, therefore reducing the occurrence of adverse pregnancy outcomes.

The role of insufficient copper in lipid synthesis and fatty-liver disease.

PubMed

Morrell, Austin; Tallino, Savannah; Yu, Lei; Burkhead, Jason L

2017-04-01

The essential transition metal copper is important in lipid metabolism, redox balance, iron mobilization, and many other critical processes in eukaryotic organisms. Genetic diseases where copper homeostasis is disrupted, including Menkes disease and Wilson disease, indicate the importance of copper balance to human health. The severe consequences of insufficient copper supply are illustrated by Menkes disease, caused by mutation in the X-linked ATP7A gene encoding a protein that transports copper from intestinal epithelia into the bloodstream and across the blood-brain barrier. Inadequate copper supply to the body due to poor diet quality or malabsorption can disrupt several molecular level pathways and processes. Though much of the copper distribution machinery has been described and consequences of disrupted copper handling have been characterized in human disease as well as animal models, physiological consequences of sub-optimal copper due to poor nutrition or malabsorption have not been extensively studied. Recent work indicates that insufficient copper may be important in a number of common diseases including obesity, ischemic heart disease, and metabolic syndrome. Specifically, marginal copper deficiency (CuD) has been reported as a potential etiologic factor in diseases characterized by disrupted lipid metabolism such as non-alcoholic fatty-liver disease (NAFLD). In this review, we discuss the available data suggesting that a significant portion of the North American population may consume insufficient copper, the potential mechanisms by which CuD may promote lipid biosynthesis, and the interaction between CuD and dietary fructose in the etiology of NAFLD. © 2016 IUBMB Life, 69(4):263-270, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Resistance mechanisms of Mycobacterium tuberculosis against phagosomal copper overload

PubMed Central

Rowland, Jennifer L.; Niederweis, Michael

2012-01-01

SUMMARY Mycobacterium tuberculosis is an important bacterial pathogen with an extremely slow growth rate, an unusual outer membrane of very low permeability and a cunning ability to survive inside the human host despite a potent immune response. A key trait of M. tuberculosis is to acquire essential nutrients while still preserving its natural resistance to toxic compounds. In this regard, copper homeostasis mechanisms are particularly interesting, because copper is an important element for bacterial growth, but copper overload is toxic. In M. tuberculosis at least two enzymes require copper as a cofactor: the Cu/Zn-superoxide dismutase SodC and the cytochrome c oxidase which is essential for growth in vitro. Mutants of M. tuberculosis lacking the copper metallothionein MymT, the efflux pump CtpV and the membrane protein MctB are more susceptible to copper indicating that these proteins are part of a multipronged system to balance intracellular copper levels. Recent evidence showed that part of copper toxicity is a reversible damage of accessible Fe-S clusters of dehydratases and the displacement of other divalent cations such as zinc and manganese as cofactors in proteins. There is accumulating evidence that macrophages use copper to poison bacteria trapped inside phagosomes. Here, we review the rapidly increasing knowledge about copper homeostasis mechanisms in M. tuberculosis and contrast those with similar mechanisms in E. coli. These findings reveal an intricate interplay between the host which aims to overload the phagosome with copper and M. tuberculosis which utilizes several mechanisms to reduce the toxic effects of excess copper. PMID:22361385

Copper emissions from a high volume air sampler

NASA Technical Reports Server (NTRS)

King, R. B.; Toma, J.

1975-01-01

High volume air samplers (hi vols) are described which utilize a brush-type electric motor to power the fans used for pulling air through the filter. Anomalously high copper values were attributed to removal of copper from the commutator into the air stream due to arcing of the brushes and recirculation through the filter. Duplicate hi vols were set up under three operating conditions: (1) unmodified; (2) gasketed to prevent internal recirculation; and (3) gasketed and provided with a pipe to transport the motor exhaust some 20 feet away. The results of 5 days' operation demonstrate that hi vols can suddenly start emitting increased amounts of copper with no discernible operational indication, and that recirculation and capture on the filter can take place. Copper levels found with hi vols whose exhaust was discharged at a distance downwind were among the lowest found, and apparently provides a satisfactory solution to copper contamination.

Lead-Free Double-Base Propellant for the 2.75 Inch Rocket Motor

NASA Technical Reports Server (NTRS)

Magill, B. T.; Nauflett, G. W.; Furrow, K. W.

2000-01-01

The current MK 66 2.75 inch Rocket Motor double-base propellant contains the lead-based ballistic modifier LC-12-15 to achieve the desired plateau and mesa burning rate characteristics. The use of lead compounds poses a concern for the environment and for personal safety due to the metal's toxic nature when introduced into the atmosphere by propellant manufacture, rocket motor firing, and disposal. Copper beta-resorcylate (copper 2,4-di-hydroxy-benzoate) was successfully used in propellant as a simple modifier in the mid 1970's. This and other compounds have also been mixed with lead salts to obtain more beneficial ballistic results. Synthesized complexes of lead and copper compounds soon replaced the mixtures. The complexes incorporate the lead, copper lack of organic liquids, which allows for easier propellant processing. About ten years ago, the Indian Head Division, Naval Surface Warfare Center (NSWC), initiated an effort to develop a lead-free propellant for use in missile systems. Several lead-free propellant candidate formulations were developed. About five years ago, NSWC, in conjunction with Alliant Techsystems, Radford Army Ammunition Plant, continued ballistic modifier investigations. A four component ballistic modifier system without lead for double-base propellants that provide adequate plateau and mesa burn rate characteristics was developed and patented. The ballistic modifier's system contains bismuth subsalicylate, 1.5 percent; copper salicylate, 1.0 percent, copper stannate, 0.77 percent; and carbon black, 0.1 percent. Action time and impulse data obtained through multiple static firings indicate that the new lead-free double-base propellant, while not a match for NOSIH-AA-2, will be a very suitable replacement in the 2.75 inch Rocket Motor. Accelerated aging of the double-base propellant containing the lead-free ballistic modifier showed that it had a much higher rate of stabilizer depletion than the AA-2. A comprehensive study showed that an increased rate of stabilizer depletion occurred in propellants containing monobasic copper salicylate. The study also showed that propellants containing a mixture of bismuth subsalicylate and copper salicylate, had only about one-half the stabilizer depletion rate than those with copper salicylate alone. The copper salicylate catalyzes the decomposition of nitroglycerin, which triggers a chain of events leading to the increased rate of stabilizer depletion. A program has been initiated to coat the ballistic modifier, thus isolating it from the nitroglycerin.

Communication between the N and C Termini Is Required for Copper-stimulated Ser/Thr Phosphorylation of Cu(I)-ATPase (ATP7B)*

PubMed Central

Braiterman, Lelita T.; Gupta, Arnab; Chaerkady, Raghothama; Cole, Robert N.; Hubbard, Ann L.

2015-01-01

The Wilson disease protein ATP7B exhibits copper-dependent trafficking. In high copper, ATP7B exits the trans-Golgi network and moves to the apical domain of hepatocytes where it facilitates elimination of excess copper through the bile. Copper levels also affect ATP7B phosphorylation. ATP7B is basally phosphorylated in low copper and becomes more phosphorylated (“hyperphosphorylated”) in elevated copper. The functional significance of hyperphosphorylation remains unclear. We showed that hyperphosphorylation occurs even when ATP7B is restricted to the trans-Golgi network. We performed comprehensive phosphoproteomics of ATP7B in low versus high copper, which revealed that 24 Ser/Thr residues in ATP7B could be phosphorylated, and only four of these were copper-responsive. Most of the phosphorylated sites were found in the N- and C-terminal cytoplasmic domains. Using truncation and mutagenesis, we showed that inactivation or elimination of all six N-terminal metal binding domains did not block copper-dependent, reversible, apical trafficking but did block hyperphosphorylation in hepatic cells. We showed that nine of 15 Ser/Thr residues in the C-terminal domain were phosphorylated. Inactivation of 13 C-terminal phosphorylation sites reduced basal phosphorylation and eliminated hyperphosphorylation, suggesting that copper binding at the N terminus propagates to the ATP7B C-terminal region. C-terminal mutants with either inactivating or phosphomimetic substitutions showed little effect upon copper-stimulated trafficking, indicating that trafficking does not depend on phosphorylation at these sites. Thus, our studies revealed that copper-dependent conformational changes in the N-terminal region lead to hyperphosphorylation at C-terminal sites, which seem not to affect trafficking and may instead fine-tune copper sequestration. PMID:25666620

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit

PubMed Central

LAMB, DAVID J; AVADES, TONY Y; FERNS, GORDON AA

2001-01-01

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25–1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 ± 0.78 vs. 1.33 ± 0.46 µg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 ± 21 IU/mg tissue) compared to the other groups (187 ± 21; 239 ± 53; 201 ± 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 ± 5.5%) and a deficient diet (0 mg/day) (63.1 ± 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 ± 6.3 and 42.8 ± 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population. PMID:11703538

Correlation of Lethal Concentrations of Heavy Metals with Tissue Levels of Earthworms

DTIC Science & Technology

1988-08-01

mentioned in the contract i.e. mercury , arsenic, ’cadmium and copper. We will find out the 50 % lethal concentrations (LC50) and the smallest...concentrations, blanks, and background worm stock has been limited to copper and cadmium. In fact, mercury and arsenic request special analytical device...the other boxes but without toxic components. Contaminants to study are heavy metals : cadmium, copper and mercury , and arsenic. We chose following

Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia.

PubMed

Al-Naama, Lamia M; Hassan, Mea'ad K; Mehdi, Jawad K

2015-01-01

Sickle cell anemia (SCA) is an inherited blood disease with known complications as a result of certain pathophysiological dysfunctions. It has been suggested that an increase in oxidative stress contributes to the incidence of these changes. This study investigated the oxidant/antioxidant status of patients with SCA, and evaluated the effect of SCA on antioxidant enzymes and their cofactors. The study included 42 patients with SCA (in steady state), and a control group of 50 age-matched individuals without SCA. Serum malondialdehyde (MDA), copper, zinc, ferritin and iron levels, red blood cell (RBC) superoxide dismutase (SOD) and catalase levels were measured for the SCA and control groups. Significantly lower levels of antioxidant enzymes (RBC SOD and catalase) and higher serum MDA levels (biomarker of oxidative stress) were found in SCA patients compared to the control group (all p < 0.001). Increased levels of serum ferritin, iron and copper and decreased zinc concentrations were also found in the SCA patients compared to the control group (all p < 0.001). In the SCA group, there were significant negative correlations between MDA levels and RBC SOD, RBC catalase, and serum zinc levels (p < 0.01), while a significant positive correlation between MDA with serum copper and iron levels (p < 0.01) was observed. SCA is associated with alterations in markers of oxidative stress including an increased MDA level, decreased antioxidant enzyme levels, and altered levels of enzyme cofactors (zinc, copper, and iron). This suggests that these antioxidant enzymes could be used as effective therapeutic targets for the treatment of this disease and supplementation of patients with substances with antioxidant properties may reduce the complications of this disease.

'Systems toxicology' approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus.

PubMed

Bundy, Jacob G; Sidhu, Jasmin K; Rana, Faisal; Spurgeon, David J; Svendsen, Claus; Wren, Jodie F; Stürzenbaum, Stephen R; Morgan, A John; Kille, Peter

2008-06-03

New methods are needed for research into non-model organisms, to monitor the effects of toxic disruption at both the molecular and functional organism level. We exposed earthworms (Lumbricus rubellus Hoffmeister) to sub-lethal levels of copper (10-480 mg/kg soil) for 70 days as a real-world situation, and monitored both molecular (cDNA transcript microarrays and nuclear magnetic resonance-based metabolic profiling: metabolomics) and ecological/functional endpoints (reproduction rate and weight change, which have direct relevance to population-level impacts). Both of the molecular endpoints, metabolomics and transcriptomics, were highly sensitive, with clear copper-induced differences even at levels below those that caused a reduction in reproductive parameters. The microarray and metabolomic data provided evidence that the copper exposure led to a disruption of energy metabolism: transcripts of enzymes from oxidative phosphorylation were significantly over-represented, and increases in transcripts of carbohydrate metabolising enzymes (maltase-glucoamylase, mannosidase) had corresponding decreases in small-molecule metabolites (glucose, mannose). Treating both enzymes and metabolites as functional cohorts led to clear inferences about changes in energetic metabolism (carbohydrate use and oxidative phosphorylation), which would not have been possible by taking a 'biomarker' approach to data analysis. Multiple post-genomic techniques can be combined to provide mechanistic information about the toxic effects of chemical contaminants, even for non-model organisms with few additional mechanistic toxicological data. With 70-day no-observed-effect and lowest-observed-effect concentrations (NOEC and LOEC) of 10 and 40 mg kg-1 for metabolomic and microarray profiles, copper is shown to interfere with energy metabolism in an important soil organism at an ecologically and functionally relevant level.

The interplay between siderophore secretion and coupled iron and copper transport in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120.

PubMed

Nicolaisen, Kerstin; Hahn, Alexander; Valdebenito, Marianne; Moslavac, Suncana; Samborski, Anastazia; Maldener, Iris; Wilken, Corinna; Valladares, Ana; Flores, Enrique; Hantke, Klaus; Schleiff, Enrico

2010-11-01

Iron uptake is essential for Gram-negative bacteria including cyanobacteria. In cyanobacteria, however, the iron demand is higher than in proteobacteria due to the function of iron as a cofactor in photosynthesis and nitrogen fixation, but our understanding of iron uptake by cyanobacteria stands behind the knowledge in proteobacteria. Here, two genes involved in this process in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 were identified. ORF all4025 encodes SchE, a putative cytoplasmic membrane-localized transporter involved in TolC-dependent siderophore secretion. Inactivation of schE resulted in an enhanced sensitivity to high metal concentrations and decreased secretion of hydroxamate-type siderophores. ORF all4026 encodes a predicted outer membrane-localized TonB-dependent iron transporter, IacT. Inactivation of iacT resulted in decreased sensitivity to elevated iron and copper levels. Expression of iacT from the artificial trc promoter (P(trc)) resulted in sensitization against tested metals. Further analysis showed that iron and copper effects are synergistic because a decreased supply of iron induced a significant decrease of copper levels in the iacT insertion mutant but an increase of those levels in the strain carrying P(trc)-iacT. Our results unravel a link between iron and copper homeostasis in Anabaena sp. PCC 7120. Copyright © 2010 Elsevier B.V. All rights reserved.

Lead, cadmium, chromium, cobalt, and copper in chicken feathers from Tuskegee, Alabama

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, A.T.; Love, M.J.; Booker, T.

1994-12-31

The feather has been widely used as a indicator tissue of metal exposure in birds. The feathers were collected from Tuskegee University poultry farm (TUPF) and Harrison Poultry farm (HPF) chicken and analyzed by Inductively Coupled Plasma Atomic Emission Spectroscopy for lead, cadmium, cobalt, chromium, and copper contaminations. The mean levels of lead, cadmium, cobalt, chromium, and copper in TUPF chicken were 3.67, 0.13, 12.23, 0.22, and 7.71 ppm, respectively, and in HPF chicken were 5.32, 0.096, 11.03, 0.15, and 8.06 ppm, respectively. The mean levels of these metals did not show any significant difference between TUPF and HPF chicken.

Biotin Decorated Gold Nanoparticles for Targeted Delivery of a Smart-Linked Anticancer Active Copper Complex: In Vitro and In Vivo Studies.

PubMed

Pramanik, Anup K; Siddikuzzaman; Palanimuthu, Duraippandi; Somasundaram, Kumaravel; Samuelson, Ashoka G

2016-12-21

The synthesis and anticancer activity of a copper(II) diacetyl-bis(N4-methylthiosemicarbazone) complex and its nanoconjugates are reported. The copper(II) complex is connected to a carboxylic acid group through a cleavable disulfide link to enable smart delivery. The copper complex is tethered to highly water-soluble 20 nm gold nanoparticles (AuNPs), stabilized by amine terminated lipoic acid-polyethylene glycol (PEG). The gold nanoparticle carrier was further decorated with biotin to achieve targeted action. The copper complex and the conjugates with and without biotin, were tested against HeLa and HaCaT cells. They show very good anticancer activity against HeLa cells, a cell line derived from cervical cancer and are less active against HaCaT cells. Slow and sustained release of the complex from conjugates is demonstrated through cleavage of disulfide linker in the presence of glutathione (GSH), a reducing agent intrinsically present in high concentrations within cancer cells. Biotin appended conjugates do not show greater activity than conjugates without biotin against HeLa cells. This is consistent with drug uptake studies, which suggests similar uptake profiles for both conjugates in vitro. However, in vivo studies using a HeLa cell xenograft tumor model shows 3.8-fold reduction in tumor volume for the biotin conjugated nanoparticle compared to the control whereas the conjugate without biotin shows only 2.3-fold reduction in the tumor volume suggesting significant targeting.

SYNTHETIC COPPER-CONTAINING PARTICLES ENHANCE ALLERGIC AIRWAY RESPONSES IN MICE

EPA Science Inventory

Respiratory morbidity and mortality associated with increases in ambient levels of particulate matter (PM) may be dependent on particle elemental composition. Particle-associated metals such as copper may catalyze formation of reactive oxygen species leading to inflammation and l...

In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and chlorophyllin analogs

PubMed Central

McCook, John P; Dorogi, Peter L; Vasily, David B; Cefalo, Dustin R

2015-01-01

Background Inhibitors of hyaluronidase are potent agents that maintain hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and anti-microbial agents. Sodium copper chlorophyllin complex is being used therapeutically as a component in anti-aging cosmeceuticals, and has been shown to have anti-hyaluronidase activity. In this study we evaluated various commercial lots of sodium copper chlorophyllin complex to identify the primary small molecule constituents, and to test various sodium copper chlorophyllin complexes and their small molecule analog compounds for hyaluronidase inhibitory activity in vitro. Ascorbate analogs were tested in combination with copper chlorophyllin complexes for potential additive or synergistic activity. Materials and methods For hyaluronidase activity assays, dilutions of test materials were evaluated for hydrolytic activity of hyaluronidase by precipitation of non-digested hyaluronate by measuring related turbidity at 595 nm. High-performance liquid chromatography and mass spectroscopy was used to analyze and identify the primary small molecule constituents in various old and new commercial lots of sodium copper chlorophyllin complex. Results The most active small molecule component of sodium copper chlorophyllin complex was disodium copper isochlorin e4, followed by oxidized disodium copper isochlorin e4. Sodium copper chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase inhibitory activity down to 10 µg/mL. The oxidized form of copper isochlorin e4 disodium salt had substantial hyaluronidase inhibitory activity at 100 µg/mL but not at 10 µg/mL. Ascorbate derivatives did not enhance the hyaluronidase inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs were always the dominant components of the small molecule content of the commercial lots tested; oxidized copper isochlorin e4 was found in increased concentrations in older compared to newer lots tested. Conclusion These results support the concept of using the hyaluronidase inhibitory activity of sodium copper chlorophyllin complex to increase the hyaluronic acid level of the dermal extracellular matrix for the improvement of the appearance of aging facial skin. PMID:26300653

In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and chlorophyllin analogs.

PubMed

McCook, John P; Dorogi, Peter L; Vasily, David B; Cefalo, Dustin R

2015-01-01

Inhibitors of hyaluronidase are potent agents that maintain hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and anti-microbial agents. Sodium copper chlorophyllin complex is being used therapeutically as a component in anti-aging cosmeceuticals, and has been shown to have anti-hyaluronidase activity. In this study we evaluated various commercial lots of sodium copper chlorophyllin complex to identify the primary small molecule constituents, and to test various sodium copper chlorophyllin complexes and their small molecule analog compounds for hyaluronidase inhibitory activity in vitro. Ascorbate analogs were tested in combination with copper chlorophyllin complexes for potential additive or synergistic activity. For hyaluronidase activity assays, dilutions of test materials were evaluated for hydrolytic activity of hyaluronidase by precipitation of non-digested hyaluronate by measuring related turbidity at 595 nm. High-performance liquid chromatography and mass spectroscopy was used to analyze and identify the primary small molecule constituents in various old and new commercial lots of sodium copper chlorophyllin complex. The most active small molecule component of sodium copper chlorophyllin complex was disodium copper isochlorin e4, followed by oxidized disodium copper isochlorin e4. Sodium copper chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase inhibitory activity down to 10 µg/mL. The oxidized form of copper isochlorin e4 disodium salt had substantial hyaluronidase inhibitory activity at 100 µg/mL but not at 10 µg/mL. Ascorbate derivatives did not enhance the hyaluronidase inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs were always the dominant components of the small molecule content of the commercial lots tested; oxidized copper isochlorin e4 was found in increased concentrations in older compared to newer lots tested. These results support the concept of using the hyaluronidase inhibitory activity of sodium copper chlorophyllin complex to increase the hyaluronic acid level of the dermal extracellular matrix for the improvement of the appearance of aging facial skin.

Neutral Red versus MTT assay of cell viability in the presence of copper compounds.

PubMed

Gomez Perez, Mariela; Fourcade, Lyvia; Mateescu, Mircea Alexandru; Paquin, Joanne

2017-10-15

Copper is essential for numerous physiological functions, and copper compounds may display therapeutic as well as cytotoxic effects. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay is a standard test largely used in cytotoxicity studies. This report shows that low micromolar levels of copper compounds such as Cu(II)Urea 2 , Cu(II)Ser 2 and CuCl 2 can interfere with the MTT assay making improper the detection of formazan product of MTT reduction. Comparatively, the Neutral Red assay appears to be sensitive and showing no interference with these compounds. The lactate dehydrogenase alternative assay cannot be used because of inhibitory effect of these copper compounds on the enzyme activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk assessment on mixture toxicity of arsenic, zinc and copper intake from consumption of milkfish, Chanos chanos (Forsskål), cultured using contaminated groundwater in Southwest Taiwan.

PubMed

Lin, Ming-Chao

2009-07-01

Studies on bioaccumulation of arsenic, zinc, and copper in freshwater-cultured milkfish were carried out to assess the risks on human health. The arsenic, zinc, and copper levels in milkfish showed significant positive correlations to the arsenic, zinc, and copper concentrations in pond water. The hazard index of arsenic, zinc, and copper mixture for intake of milkfish (1.75 +/- 0.65) demonstrated that intake of in this way contaminated milkfish will result in non-carcinogenic risk. The target cancer risk of arsenic for intake of the milkfish (2.74 x 10(-4) +/- 1.18 x 10(-4)) indicated that the inhabitants were exposed to arsenic pollution with carcinogenic risk.

Haemolymph from Mytilus galloprovincialis: Response to copper and temperature challenges studied by (1)H-NMR metabonomics.

PubMed

Digilio, Giuseppe; Sforzini, Susanna; Cassino, Claudio; Robotti, Elisa; Oliveri, Caterina; Marengo, Emilio; Musso, Davide; Osella, Domenico; Viarengo, Aldo

2016-01-01

Numerous studies on molluscs have been carried out to clarify the physiological roles of haemolymph serum proteins and haemocytes. However, little is known about the presence and functional role of the serum metabolites. In this study, Nuclear Magnetic Resonance (NMR) was used to assess whether changes of the metabolic profile of Mytilus galloprovincialis haemolymph may reflect alterations of the physiological status of the organisms due to environmental stressors, namely copper and temperature. Mussel haemolymph was taken from the posterior adductor muscle after a 4-day exposure to ambient (16 °C) or high temperature (24 °C) and in the absence or presence (5 μg/L, 20 μg/L, or 40 μg/L) of sublethal copper (Cu(2+)). The total glutathione (GSH) concentration in the haemolymph of both control and treated mussels was minimal, indicating the absence of significant contaminations by muscle intracellular metabolites due to the sampling procedure. In the (1)H-NMR spectrum of haemolymph, 27 metabolites were identified unambiguously. The separate and combined effects of exposure to copper and temperature on the haemolymph metabolic profile were assessed by Principal Component Analysis (PCA) and Ranking-PCA multivariate analysis. Changes of the metabolomic profile due to copper exposure at 16 °C became detectable at a dose of 20 μg/L copper. Alanine, lysine, serine, glutamine, glycogen, glucose and protein aliphatics played a major role in the classification of the metabolic changes according to the level of copper exposition. High temperature (24 °C) and high copper levels caused a coherent increase of a common set of metabolites (mostly glucose, serine, and lysine), indicating that the metabolic impairment due to high temperature is enforced by the presence of copper. Overall, the results demonstrate that, as for human blood plasma, the analysis of haemolymph metabolites represents a promising tool for the diagnosis of pollutant-induced stress syndrome in marine mussels. Copyright © 2016 Elsevier Inc. All rights reserved.

A deleterious interaction between copper deficiency and sugar ingestion may be the missing link in heart disease.

PubMed

Aliabadi, Hamidreza

2008-01-01

Copper deficiency plays a vital role in atherogenesis. To the long list of risk factors for atherosclerotic cardiovascular disease should be added the deleterious interaction between copper deficiency and carbohydrate consumption. Here we critically evaluate the role of copper in the diet and its role as a possible etiological factor in the development of cardiovascular disease. A possible mechanism for the development of heart disease due to copper deficiency is proposed. There are many known risk factors for the development of heart disease, including hyperlipidemia and hypertension; however, little emphasis has been placed on the role of copper on heart disease. Over the last couple of decades, dietary copper deficiency has been shown to cause a variety of metabolic changes, including hypercholesterolemia, hypertriglyceridemia, hypertension, and glucose intolerance. Interestingly, these changes are common in the United States population and they are known risk factors for heart disease. Further research in this field is warranted considering the profound implications to people in the United States and around the world who consume processed foods marginally deficient in copper and replete with sugar. The only nutritional condition with signs and symptoms of atherosclerotic cardiovascular disease may be copper deficiency. Improving levels of copper in the diet, by appropriate food selection or by addition of a daily multi-vitamin, is recommended.

Dynamics of the metal binding domains and regulation of the human copper transporters ATP7B and ATP7A.

PubMed

Yu, Corey H; Dolgova, Natalia V; Dmitriev, Oleg Y

2017-04-01

Copper transporters ATP7A and ATP7B regulate copper levels in the human cells and deliver copper to the biosynthetic pathways. ATP7A and ATP7B belong to the P-type ATPases and share much of the domain architecture and the mechanism of ATP hydrolysis with the other, well-studied, enzymes of this type. A unique structural feature of the copper ATPases is the chain of six cytosolic metal-binding domains (MBDs), which are believed to be involved in copper-dependent regulation of the activity and intracellular localization of these enzymes. Although the structures of all the MBDs have been solved, the mechanism of copper-dependent regulation of ATP7B and ATP7A, the roles of individual MBDs, and the relationship between the regulatory and catalytic copper binding are still unknown. We describe the structure and dynamics of the MBDs, review the current knowledge about their functional roles and propose a mechanism of regulation of ATP7B by copper-dependent changes in the dynamics and conformation of the MBD chain. Transient interactions between the MBDs, rather than transitions between distinct static conformations are likely to form the structural basis of regulation of the ATP-dependent copper transporters in human cells. © 2016 IUBMB Life, 69(4):226-235, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Copper Homeostasis in Escherichia coli and Other Enterobacteriaceae.

PubMed

Rensing, Christopher; Franke, Sylvia

2007-04-01

An interesting model for studying environmental influences shaping microbial evolution is provided by a multitude of copper resistance and copper homeostasis determinants in enteric bacteria. This review describes these determinants and tries to relate their presence to the habitat of the respective organism, as a current hypothesis predicts that the environment should determine an organism's genetic makeup. In Escherichia coli there are four regulons that are induced in the presence of copper. Two, the CueR and the CusR regulons, are described in detail. A central component regulating intracellular copper levels, present in all free-living enteric bacteria whose genomes have so far been sequenced, is a Cu(I)translocating P-type ATPase. The P-type ATPase superfamily is a ubiquitous group of proteins involved in the transport of charged substrates across biological membranes. Whereas some components involved in copper homeostasis can be found in both anaerobes and aerobes, multi-copper oxidases (MCOs) implicated in copper tolerance in E. coli, such as CueO and the plasmid-based PcoA, can be found only in aerobic organisms. Several features indicate that CueO, PcoA, and other related MCOs are specifically adapted to combat copper-mediated oxidative damage. In addition to these well-characterized resistance operons, there are numerous other genes that appear to be involved in copper binding and trafficking that have not been studied in great detail. SilE and its homologue PcoE, for example, are thought to effect the periplasmic binding and sequestration of silver and copper, respectively.

Earth Observations taken by the Expedition 13 crew

NASA Image and Video Library

2006-08-02

ISS013-E-63766 (2 Aug. 2006) --- Berkeley Pit and Butte, Montana are featured in this image photographed by an Expedition 13 crewmember on the International Space Station. The city of Butte, Montana has long been a center of mining activity. Underground mining of copper began in Butte in the 1870s, and by 1901 underground workings had extended to the groundwater table. Thus began the creation of an intricate complex of underground drains and pumps to lower the groundwater level and continue the extraction of copper. Water extracted from the mines was so rich in dissolved copper sulfate that it was also "mined" (by chemical precipitation) for the copper it contained. In 1955, the Anaconda Copper Mining Company began open-pit mining for copper in what is now know as the Berkeley Pit (dark oblong area in center). The mine took advantage of the existing subterranean drainage and pump network to lower groundwater until 1982, when the new owner ARCO suspended operations at the mine. The groundwater level swiftly rose, and today water in the Pit is more than 900 feet deep. Many features of the mine workings are visible in this image such as the many terraced levels and access roadways of the open mine pits (gray and tan sculptured surfaces). A large gray tailings pile of waste rock and an adjacent tailings pond are visible to the north of the Berkeley Pit. Color changes in the tailings pond are due primarily to changing water depth. The Berkeley Pit is listed as a federal Superfund site due to its highly acidic water, which contains high concentrations of metals such as copper and zinc. The Berkeley Pit receives groundwater flowing through the surrounding bedrock and acts as a "terminal pit" or sink for these heavy metal-laden waters. Ongoing efforts include regulation of water flow into the pit to reduce filling of the Pit and potential release of contaminated water into local aquifers or surface streams.

Copper induced oxidative stresses, antioxidant responses and phytoremediation potential of Moso bamboo (Phyllostachys pubescens)

NASA Astrophysics Data System (ADS)

Chen, Junren; Shafi, Mohammad; Li, Song; Wang, Ying; Wu, Jiasen; Ye, Zhengqian; Peng, Danli; Yan, Wenbo; Liu, Dan

2015-09-01

Moso bamboo is recognized as phytoremediation plant due to production of huge biomass and high tolerance in stressed environment. Hydroponics and pot experiments were conducted to investigate mechanism of copper tolerance and to evaluate copper accumulation capacity of Moso bamboo. In hydroponics experiment there was non significant variation in MDA contents of leaves compared with control. SOD and POD initially indicated enhancing trend with application of 5 μM Cu and then decreased consistently with application of 25 and 100 μM Cu. Application of each additional increment of copper have constantly enhanced proline contents while maximum increase of proline was observed with application of 100 μM copper. In pot experiment chlorophyll and biomass initially showed increasing tendency and decreased gradually with application of each additional increment of Cu. Normal growth of Moso bamboo was observed with application of 100 mg kg-1 copper. However, additional application of 300 or 600 mg kg-1 copper had significantly inhibited growth of Moso bamboo. The concentration of Cu in Moso bamboo has attained the levels of 340, 60, 23 mg kg-1 in roots, stems and leaves respectively. The vacuoles were the main organs which accumulated copper and reduced toxicity of copper as studied by TEM-DEX technology.

Copper induced oxidative stresses, antioxidant responses and phytoremediation potential of Moso bamboo (Phyllostachys pubescens)

PubMed Central

Chen, Junren; Shafi, Mohammad; Li, Song; Wang, Ying; Wu, Jiasen; Ye, Zhengqian; Peng, Danli; Yan, Wenbo; Liu, Dan

2015-01-01

Moso bamboo is recognized as phytoremediation plant due to production of huge biomass and high tolerance in stressed environment. Hydroponics and pot experiments were conducted to investigate mechanism of copper tolerance and to evaluate copper accumulation capacity of Moso bamboo. In hydroponics experiment there was non significant variation in MDA contents of leaves compared with control. SOD and POD initially indicated enhancing trend with application of 5 μM Cu and then decreased consistently with application of 25 and 100 μM Cu. Application of each additional increment of copper have constantly enhanced proline contents while maximum increase of proline was observed with application of 100 μM copper. In pot experiment chlorophyll and biomass initially showed increasing tendency and decreased gradually with application of each additional increment of Cu. Normal growth of Moso bamboo was observed with application of 100 mg kg−1 copper. However, additional application of 300 or 600 mg kg−1 copper had significantly inhibited growth of Moso bamboo. The concentration of Cu in Moso bamboo has attained the levels of 340, 60, 23 mg kg−1 in roots, stems and leaves respectively. The vacuoles were the main organs which accumulated copper and reduced toxicity of copper as studied by TEM-DEX technology. PMID:26337551

Colorimetric assay of copper ions based on the inhibition of peroxidase-like activity of MoS2 nanosheets

NASA Astrophysics Data System (ADS)

Chen, Huan; Li, Zhihong; Liu, Xueting; Zhong, Jianhai; Lin, Tianran; Guo, Liangqia; Fu, Fengfu

2017-10-01

The peroxidase-like catalytic activity of MoS2 nanomaterials has been utilized for colorimetric bioassays and medical diagnostics. However, the application of peroxidase-like catalytic activity of MoS2 nanomaterials in environmental analysis was seldom explored. Herein, copper ions were found to inhibit the peroxidase-like catalytic activity of MoS2 nanosheets, which can catalyze the oxidation of 3, 3‧, 5, 5‧-tetramethylbenzidine by H2O2 to produce a colorimetric product. Based on this finding, a simple sensitive colorimetric method for the detection of copper ions was developed. In the presence of copper ions, the absorbance and color of the solution decreased with the increasing concentration of copper ions. The color of the solution can be used to semi-quantitative on-site assay of copper ions by naked eyes. A linear relationship between the absorbance and the concentration of copper ions was observed in the range of 0.4-4.0 μmol L- 1 with a detection limit of 92 nmol L- 1, which was much lower than the maximum contaminant level of copper in drinking water legislated by the Environmental Protection Agency of USA and the World Health Organization. The method was applied to detect copper ions in environmental water samples with satisfactory results.

Transfer of Metals in Food Chain: An Example with Copper and Lettuce

NASA Astrophysics Data System (ADS)

Vincevica-Gaile, Zane; Klavins, Maris

2012-12-01

Present study investigated the possible transfer of metals in the food chain (from soil to edible plants). The experiment was done with lettuce Lactuca sativa grown in different types of soil contaminated with copper (Cu2+) in various concentrations, with or without addition of humic substances. The highest content of copper was detected in lettuce samples grown in soils with lower levels of organic matter, thus indicating the importance of soil organics in metal transfer routes and accumulation rates in plants. It was found that copper accumulation in lettuce grown in contaminated soils can be significantly reduced by the addition of humic substances.

Growth of tropical tree species and absorption of copper in soil artificially contaminated.

PubMed

Silva, R F; Andreazza, R; Da Ros, C; Dellai, A; Jacques, R J S; Scheid, D

2015-11-01

Reclamation of copper contaminated sites using forest species may be an efficient alternative to reduce the negative impact. The aim of this study was to quantify the growth and evaluate the quality of seedlings of native species at different doses of copper in the soil. The experimental design was completely randomized, with seven replications in a factorial arrangement (3×9), using three indigenous species of plants (Anadenanthera macrocarpa, Mimosa scabrella and Apuleia leiocarpa) and nine doses of copper in the soil (0, 60, 120, 180, 240, 300, 360, 420 and 480 mg kg-1).The experiment was carried out in a greenhouse which the seedlings were grown for 180 days. The experimental units were plastic pots of 125 cm3 filled with Oxisol. The results indicated that the levels of copper applied to the soil decreased the quality of seedlings and growth of Apuleia leiocarpato a lesser extent compared with Mimosa scabrella and Anadenanthera macrocarpa. Anadenanthera macrocarpa was the forest species that resulted in the lowest copper translocation from roots to shoots. In addition, the Apuleia leiocarpa exhibited high resistance and tolerance for copper in the soil and also, it is highlighted an ability for copper phytoremediation.

Increased iron supplied through Fet3p results in replicative life span extension of Saccharomyces cerevisiae under conditions requiring respiratory metabolism.

PubMed

Botta, Gabriela; Turn, Christina S; Quintyne, Nicholas J; Kirchman, Paul A

2011-10-01

We have previously shown that copper supplementation extends the replicative life span of Saccharomyces cerevisiae when grown under conditions forcing cells to respire. We now show that copper's effect on life span is through Fet3p, a copper containing enzyme responsible for high affinity transport of iron into yeast cells. Life span extensions can also be obtained by supplementing the growth medium with 1mM ferric chloride. Extension by high iron levels is still dependent on the presence of Fet3p. Life span extension by iron or copper requires growth on media containing glycerol as the sole carbon source, which forces yeast to respire. Yeast grown on glucose containing media supplemented with iron show no extension of life span. The iron associated with cells grown in media supplemented with copper or iron is 1.4-1.8 times that of cells grown without copper or iron supplementation. As with copper supplementation, iron supplementation partially rescues the life span of superoxide dismutase mutants. Cells grown with copper supplementation display decreased production of superoxide as measured by dihydroethidium staining. Copyright © 2011 Elsevier Inc. All rights reserved.

Levels of plasma ceruloplasmin protein are markedly lower following dietary copper deficiency in rodents

PubMed Central

Broderius, Margaret; Mostad, Elise; Wendroth, Krista; Prohaska, Joseph R.

2010-01-01

Ceruloplasmin (Cp) is a multicopper oxidase and the most abundant copper binding protein in vertebrate plasma. Loss of function mutations in humans or experimental deletion in mice result in iron overload consistent with a putative ferroxidase function. Prior work suggested plasma may contain multiple ferroxidases. Studies were conducted in Holtzman rats (Rattus novegicus), albino mice (Mus musculus), Cp -/- mice, and adult humans (Homo sapiens) to investigate the copper-iron interaction. Dietary copper-deficient (CuD) rats and mice were produced using a modified AIN-76A diet. Results confirmed that o-dianisidine is a better substrate than paraphenylene diamine (PPD) for assessing diamine oxidase activity of Cp. Plasma from CuD rat dams and pups, and CuD and Cp -/- mice contained no detectable Cp diamine oxidase activity. Importantly, no ferroxidase activity was detectable for CuD rats, mice, or Cp -/- mice compared to robust activity for copper-adequate (CuA) rodent controls using western membrane assay. Immunoblot protocols detected major reductions (60-90%) in Cp protein in plasma of CuD rodents but no alteration in liver mRNA levels by qRT-PCR. Data are consistent with apo-Cp being less stable than holo-Cp. Further research is needed to explain normal plasma iron in CuD mice. Reduction in Cp is a sensitive biomarker for copper deficiency. PMID:20170749

Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth muscle cell migration.

PubMed

Ashino, Takashi; Sudhahar, Varadarajan; Urao, Norifumi; Oshikawa, Jin; Chen, Gin-Fu; Wang, Huan; Huo, Yuqing; Finney, Lydia; Vogt, Stefan; McKinney, Ronald D; Maryon, Edward B; Kaplan, Jack H; Ushio-Fukai, Masuko; Fukai, Tohru

2010-09-17

Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the copper importer CTR1 (copper transporter 1) but also by the copper exporter ATP7A (Menkes ATPase), whose function is achieved through copper-dependent translocation from trans-Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth muscle cell (VSMC) migration, a key component of neointimal formation. To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration. Depletion of ATP7A inhibited VSMC migration in response to PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation promoted ATP7A translocation from the TGN to lipid rafts, which localized at the leading edge, where it colocalized with PDGF receptor and Rac1, in migrating VSMCs. Mechanistically, ATP7A small interfering RNA or CTR small interfering RNA prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced decrease in copper level and secretory copper enzyme precursor prolysyl oxidase (Pro-LOX) in lipid raft fraction, as well as PDGF-induced increase in LOX activity. In vivo, ATP7A expression was markedly increased and copper accumulation was observed by synchrotron-based x-ray fluorescence microscopy at neointimal VSMCs in wire injury model. These findings suggest that ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration via recruiting Rac1 to lipid rafts at the leading edge, as well as regulating LOX activity. This may contribute to neointimal formation after vascular injury. Our findings provide insight into ATP7A as a novel therapeutic target for vascular remodeling and atherosclerosis.

Selection of Fecal Enterococci Exhibiting tcrB-Mediated Copper Resistance in Pigs Fed Diets Supplemented with Copper † ▿

PubMed Central

Amachawadi, R. G.; Shelton, N. W.; Shi, X.; Vinasco, J.; Dritz, S. S.; Tokach, M. D.; Nelssen, J. L.; Scott, H. M.; Nagaraja, T. G.

2011-01-01

Copper, as copper sulfate, is increasingly used as an alternative to in-feed antibiotics for growth promotion in weaned piglets. Acquired copper resistance, conferred by a plasmid-borne, transferable copper resistance (tcrB) gene, has been reported in Enterococcus faecium and E. faecalis. A longitudinal field study was undertaken to determine the relationship between copper supplementation and the prevalence of tcrB-positive enterococci in piglets. The study was done with weaned piglets, housed in 10 pens with 6 piglets per pen, fed diets supplemented with a normal (16.5 ppm; control) or an elevated (125 ppm) level of copper. Fecal samples were randomly collected from three piglets per pen on days 0, 14, 28, and 42 and plated on M-Enterococcus agar, and three enterococcal isolates were obtained from each sample. The overall prevalence of tcrB-positive enterococci was 21.1% (38/180) in piglets fed elevated copper and 2.8% (5/180) in the control. Among the 43 tcrB-positive isolates, 35 were E. faecium and 8 were E. faecalis. The mean MICs of copper for tcrB-negative and tcrB-positive enterococci were 6.2 and 22.2 mM, respectively. The restriction digestion of the genomic DNA of E. faecium or E. faecalis with S1 nuclease yielded a band of ∼194-kbp size to which both tcrB and the erm(B) gene probes hybridized. A conjugation assay demonstrated cotransfer of tcrB and erm(B) genes between E. faecium and E. faecalis strains. The higher prevalence of tcrB-positive enterococci in piglets fed elevated copper compared to that in piglets fed normal copper suggests that supplementation of copper in swine diets selected for resistance. PMID:21705534

DFT study of ethyl xanthate interaction with sphalerite (1 1 0) surface in the absence and presence of copper

NASA Astrophysics Data System (ADS)

Liu, Jian; Wen, Shuming; Deng, Jiushuai; Chen, Xiumin; Feng, Qicheng

2014-08-01

The interaction among sphalerite (1 1 0) surface, copper and ethyl xanthate (EX) was simulated using the density functional theory (DFT). The results of DFT indicate that four types of stable interaction models exist among sphalerite surface, copper and EX, i.e., EX interacts with the Cu substituted for Zn, Cu adsorbed on the top site of S, Cu adsorbed on the bridge site of S and Cu(OH)2 adsorbed on the sphalerite surface. The four interaction models can result in the activation flotation of sphalerite. Density of states (DOS) analysis shows that the energy level discrepancy of the Zn 3d orbital in ZnS and the bonding S 3p orbital in EX results in the weak adsorption of EX on un-activated sphalerite surface. However, after copper activation, the Cu 3d orbital peak and bonding S 3p orbital peak are just maximally overlapped nearby the Fermi level. This study provides an insight into the nature that sphalerite responds not well to EX and also a comprehensive understanding on the possible interaction cases existing among sphalerite surface, copper and EX.

Aided Phytostabilization of Copper Contaminated Soils with L. Perenne and Mineral Sorbents as Soil Amendments

NASA Astrophysics Data System (ADS)

Radziemska, Maja

2017-09-01

The present study was designed to assess phytostabilization strategies for the treatment of soil co-contaminated by increasing levels of copper with the application mineral amendments (chalcedonite, zeolite, dolomite). From the results it will be possible to further elucidate the benefits or potential risks derived from the application of different types of mineral amendments in the remediation of a copper contaminated soil. A glasshouse pot experiment was designed to evaluate the potential use of different amendments as immobilizing agents in the aided phytostabilization of Cu-contaminated soil using ryegrass (Lolium perenne L.). The content of trace elements in plants and total in soil, were determined using the method of spectrophotometry. All of the investigated element contents in the tested parts of L. perenne were significantly different in the case of applying mineral amendments to the soil, as well as increasing concentrations of copper. The greatest average above-ground biomass was observed for soil amended with chalcedonite. In this experiment, all analyzed metals accumulated predominantly in the roots of the tested plant. In general, applying mineral amendments to soil contributed to decreased levels of copper concentrations.

Effect of low-level copper and pentachlorophenol exposure on various early life stages of Xenopus laevis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fort, D.J.; Stover, E.L.

1996-12-31

An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis, was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorphenol, from 0 d to 4 d (standard Frog Embryo Teratogenesis Assay--Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased in eachmore » successive time period. Longer-term exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5 {micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less

Electrochemical techniques implementation for corrosion rate measurement in function of humidity level in grounding systems (copper and stainless steel) in soil samples from Tunja (Colombia)

NASA Astrophysics Data System (ADS)

Salas, Y.; Guerrero, L.; Blanco, J.; Jimenez, C.; Vera-Monroy, S. P.; Mejía-Camacho, A.

2017-12-01

In this work, DC electrochemical techniques were used to determine the corrosion rate of copper and stainless-steel electrodes used in grounding, varying the level of humidity, in sandy loam and clay loam soils. The maximum corrosion potentials were: for copper -211 and -236mV and for stainless steel of -252 and -281mV, in sandy loam and clay loam respectively, showing that in sandy loam the values are higher, about 30mV. The mechanism by which steel controls corrosion is by diffusion, whereas in copper it is carried out by transfer of mass and charge, which affects the rate of corrosion, which in copper reached a maximum value of 5mm/yr and in Steel 0.8mm/yr, determined by Tafel approximations. The behaviour of the corrosion rate was mathematically adjusted to an asymptotic model that faithfully explains the C.R. as a function of humidity, however, it is necessary to define the relation between the factor □ established in the model and the precise characteristics of the soil, such as the permeability or quantity of ions present.

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

PubMed Central

Fieten, Hille; Gill, Yadvinder; Martin, Alan J.; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G.; Spee, Bart; van den Ingh, Ted S. G. A. M.; Martens, Ellen C. C. P.; Festa, Paola; Chesi, Giancarlo; van de Sluis, Bart; Houwen, Roderick H. J. H.; Watson, Adrian L.; Aulchenko, Yurii S.; Hodgkinson, Victoria L.; Zhu, Sha; Petris, Michael J.; Polishchuk, Roman S.; Leegwater, Peter A. J.; Rothuizen, Jan

2016-01-01

ABSTRACT The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional variants in ATP7A and ATP7B contributes to the biological understanding of protein function, with relevance for future development of therapy. PMID:26747866

Heavy metal hazards of sachet water in Nigeria.

PubMed

Orisakwe, Orish Ebere; Igwilo, Innocent O; Afonne, Onyenmechi Johnson; Maduabuchi, John-Moses Ugwuona; Obi, Ejeatuluchukwu; Nduka, John C

2006-01-01

The authors assessed sachet water samples sold in Eastern Nigeria. Using an atomic absorption spectrophotometer, they analyzed levels of lead, cadmium, copper, and nickel. They also analyzed other parameters, such as nitrates, sulfates, chlorides, salinity, total hardness, biological oxygen demand, total dissolved solids, and pH level. Lead levels ranged from 0.002 to 0.036 mg/L in the samples; 5 samples (12.2%) had lead levels above the maximum contaminant level (MCL; 0.015 mg/L). Lead was not detectable in 20 samples (48.8%). Cadmium levels ranged from 0.002 to 0.036 mg/L and exceeded the MCL of 0.005 mg/L in 8 samples (19.5%); it was not detectable in 23 samples (56.1%). Copper was not detected in 2 (0.05%) of the samples. Its range was between 0.018 and 1.401 mg/L. Two samples (0.05%) had copper levels above the MCL (1.30 mg/L). Nickel levels ranged from 0.003 to 0.050 mg/l. The biological oxygen demand of the samples ranged from 3.20 to 36.80 mg/L. Other parameters were normal. The authors found that some of the sachet waters contain heavy metals, and consumers may be exposed to hazards.

77 FR 26039 - Notice of Availability of the Final Environmental Impact Statement for the Phoenix Copper Leach...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

... Protection Agency (EPA) publishes its notice in the Federal Register. ADDRESSES: Copies of the FEIS for the...) may call the Federal Information Relay Service (FIRS) at 1-800- 877-8339 to contact the above... committed environmental protection measures, the BLM's preferred alternative is the proposed action. The...

Copper tolerance of the thermoacidophilic archaeon Sulfolobus metallicus: possible role of polyphosphate metabolism.

PubMed

Remonsellez, Francisco; Orell, Alvaro; Jerez, Carlos A

2006-01-01

It has been postulated that inorganic polyphosphate (polyP) and transport of metal-phosphate complexes could participate in heavy metal tolerance in some bacteria. To study if such a system exists in archaea, the presence of polyP was determined by the electron energy loss spectroscopy (EELS) procedure and quantified by using specific enzymic methods in Sulfolobus acidocaldarius, Sulfolobus metallicus and Sulfolobus solfataricus. All three micro-organisms synthesized polyP during growth, but only S. metallicus greatly accumulated polyP granules. The differences in the capacity to accumulate polyP between these archaea may reflect adaptive responses to their natural environment. Thus, S. metallicus could grow in and tolerate up to 200 mM copper sulfate, with a concomitant decrease in its polyP levels with increasing copper concentrations. On the other hand, S. solfataricus could not grow in or tolerate more than 1-5 mM copper sulfate, most likely due to its low levels of polyP. Shifting S. metallicus cells to copper sulfate concentrations up to 100 mM led to a rapid increase in their exopolyphosphatase (PPX) activity which was concomitant in time with a decrease in their polyP levels and a stimulation of phosphate efflux. Furthermore, copper in the range of 10 microM greatly stimulated PPX activity in cell-free extracts from S. metallicus. The results strongly suggest that a metal tolerance mechanism mediated through polyP is functional in members of the genus Sulfolobus. This ability to accumulate and hydrolyse polyP may play an important role not only in the survival of these micro-organisms in sulfidic mineral environments containing high toxic metals concentrations, but also in their applications in biomining.

RP-1 Thermal Stability and Copper Based Materials Compatibility Study

NASA Technical Reports Server (NTRS)

Stiegemeier, B. R.; Meyer, M. L.; Driscoll, E.

2005-01-01

A series of electrically heated tube tests was performed at the NASA Glenn Research Center s Heated Tube Facility to investigate the effect that sulfur content, test duration, and tube material play in the overall thermal stability and materials compatibility characteristics of RP-1. Scanning-electron microscopic (SEM) analysis in conjunction with energy dispersive spectroscopy (EDS) were used to characterize the condition of the tube inner wall surface and any carbon deposition or corrosion formed during these runs. Results of the parametric study indicate that tests with standard RP-1 (total sulfur -23 ppm) and pure copper tubing are characterized by a depostion/deposit shedding process producing local wall temperature swings as high as 500 F. The effect of this shedding is to keep total carbon deposition levels relatively constant for run times from 20 minutes up to 5 hours, though increasing tube pressure drops were observed in all runs. Reduction in the total sulfur content of the fuel from 23 ppm to less than 0.1 ppm resulted in the elimination of deposit shedding, local wall temperature variation, and the tube pressure drop increases that were observed in standard sulfur level RP-1 tests. The copper alloy GRCop-84, a copper alloy developed specifically for high heat flux applications, was found to exhibit higher carbon deposition levels compared to identical tests performed in pure copper tubes. Results of the study are consistent with previously published heated tube data which indicates that small changes in fuel total sulfur content can lead to significant differences in the thermal stability of kerosene type fuels and their compatibility with copper based materials. In conjunction with the existing thermal stability database, these findings give insight into the feasibility of cooling a long life, high performance, high-pressure liquid rocket combustor and nozzle with RP-1.

Studies on Zinc and Copper Ion in Relation to Wound Healing in Male and Female West African Dwarf Goats.

PubMed

Olaifa, A K; Fadason, S T

2017-03-06

Wound healing remains a challenging clinical problem for which precise and efficient management is essential in order to curtail morbidity and mortality. Wound healing has been shown to depend upon the availability of appropriate trace elements like copper and zinc which serve as enzyme cofactors and structural components in tissue repair. This study aims at evaluating the distribution of zinc and copper found in the hair as well as skin during epidermal wound healing. Adult and healthy West African dwarf (WAD) goats of both sexes fed with concentrate, grass, cassava peel and water ad libitum were used. The animals were housed for three weeks before commencement of the experiments. Epidermal wounds were created on the trunks of all the goats using cardboard template of 1cm². Progressive changes in wound contraction were monitored grossly by placing clean and sterile venier calliper on the wound margin. Hair and skin elemental (copper and zinc) analyses were done using atomic absorption spectroscopy (AAS). Significant increases in Cu level were observed in the female hair compared with that of males. There were significant increases in the Zn levels of the females' hair compared with the males. The wound healed faster in female goat compared with the males. The ratio of copper to zinc is clinically more important than the concentration of either of these trace metals. The pattern of distribution between zinc and copper concentration in the skin and hair of the male and female goats observed in this study could be added factor responsible for early wound healing in female. Therefore, our findings suggest that the distribution in the Cu and Zinc level in skin and hair of both male and female goats could also be a factor for wound healing in the animals.

The treatment of Wilson's disease, a rare genetic disorder of copper metabolism.

PubMed

Purchase, Rupert

2013-01-01

Wilson's disease is a rare autosomal recessive disease characterised by the deposition of copper in the brain, liver; cornea, and other organs. The overload of copper inevitably leads to progressive liver and neurological dysfunction. Copper overload in patients with Wilson's disease is caused by impairment to the biliary route for excretion of dietary copper A combination of neurological, psychiatric and hepatic symptoms can make the diagnosis of Wilson's disease challenging. Most symptoms appear in the second and third decades of life. The disease affects between one in 30,000 and one in 100,000 individuals, and is fatal if left untreated. Five drugs are currently available to treat Wilson's disease: British Anti-Lewisite; D-penicillamine; trientine; zinc sulfate or acetate; and ammonium tetrathiomolybdate. Each drug can reduce copper levels and/or transform copper into a metabolically inert and unavailable form in the patient. The discovery and introduction of these five drugs owes more to the inspiration of a few dedicated physicians and agricultural scientists than to the resources of the pharmaceutical industry.

Improved Electroformed Structural Copper and Copper Alloys

NASA Technical Reports Server (NTRS)

Malone, G. A.; Hudson, W.; Babcock, B.; Edwards, R.

1998-01-01

Electroforming offers a superior means for fabricating internally cooled heat exchangers and structures subjected to thermal environments. Copper is deposited from many such applications because of the good thermal conductivity. It suffers from mediocre yield strength as a structural material and loses mechanical strength at intermediate temperatures. Mechanical properties similar to those of electroformed nickel are desired. Phase 1 examined innovative means to improve deposited copper structural performance. Yield strengths as high as 483 MPa (70 ksi) were obtained with useful ductility while retaining a high level of purity essential to good thermal conductivity. Phase 2 represents a program to explore new additive combinations in copper electrolytes to produce a more fine, equiaxed grain which can be thermally stabilized by other techniques such as alloying in modest degrees and dispersion strengthening. Evaluation of new technology - such as the codeposition of fullerness (diamond-like) particles were made to enhance thermal conductivity in low alloys. A test fire quality tube-bundle engine was fabricated using these copper property improvement concepts to show the superiority of the new coppers and fabrications methods over competitive technologies such as brazing and plasma deposition.

Use of Electrodeposition for Sample Preparation and Rejection Rate Prediction for Assay of Electroformed Ultra High Purity Copper for 232Th and 238U Prior to Inductively Coupled Plasma Mass Spectrometry (ICP/MS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoppe, Eric W.; Aalseth, Craig E.; Brodzinski, Ronald L.

The search for neutrinoless double beta decay in 76Ge has driven the need for ultra-low background Ge detectors shielded by electroformed copper of ultra-high radiopurity (<0.1µBq/kg). Although electrodeposition processes are almost sophisticated enough to produce copper of this purity, to date there are no methods sensitive enough to assay it. Inductively-coupled plasma mass spectrometry (ICP/MS) can detect thorium and uranium at femtogram levels, but in the past, this assay has been hindered by high copper concentrations in the sample. Electrodeposition of copper samples removes copper from the solution while selectively concentrating thorium and uranium contaminants to be assayed by ICP/MS.more » Spiking 232Th and 238U into the plating bath simulates low purity copper and allows for the calculation of the electrochemical rejection rate of thorium and uranium in the electroplating system. This rejection value will help to model plating bath chemistry.« less

Accumulation and effects of copper on aquatic macrophytes Potamogeton pectinatus L.: Potential application to environmental monitoring and phytoremediation.

PubMed

Costa, Marcela Brandão; Tavares, Francesca Valêncio; Martinez, Claudia Bueno; Colares, Ioni Gonçalves; Martins, Camila de Martinez Gaspar

2018-07-15

This study investigated the ability of Potamogeton pectinatus L. to accumulate copper and its effects on plants. In accumulation tests, macrophytes were exposed (96 h) to different copper concentrations (0-1000 µM) and the metal was measured in media and plant tissues (roots, stems and leaves) to determine the bioconcentration factor (BCF). Plants accumulated high concentrations of copper in a dose-dependent manner and roots was the main organ for copper accumulation. However, the more copper increased in water, the more BCF values decreased. It may be due to either saturation of copper uptake or down-regulation of metal uptake by plants. In the physiological and morphological analyses, plants were kept (96 h) in Hoagland nutrient solution without copper, in full Hoagland solution (0.5 µM Cu) and in Hoagland medium with copper from 1 to 100 µM. The absence and the presence of copper above to 1 µM inhibited photosynthesis. Chlorophylls and carotenoid levels also decreased with the excess of copper, a fact that may have affected the photosystem II-dependent of chlorophyll and caused photosynthesis suppression. Only macrophytes at 10 µM Cu showed decrease in length and number of leaves on the 10th day of the test, when they died. Chlorosis and necrosis were observed in control groups and groups with extra copper, but not in Hoalgand group. Overall, the macrophyte P. pectinatus can be considered a suitable plant for monitoring environments contaminated by copper, based on results of copper accumulation in the plant, decrease in pigment concentration and presence of chlorosis and necrosis. However, values of BCF based on fresh water tissues was not proper to indicate the use of P. pectinatus for cleaning environments contaminated by copper. Copyright © 2018 Elsevier Inc. All rights reserved.

Productivity and Diversity of Phytoplankton in Relation to Copper Levels in San Diego Bay.

DTIC Science & Technology

1980-03-01

phytoplankton assemblages taken from the PIER (P), INLET (1), and NAVY (N) sites from July 1978 through June 1979... 15 Figure 7. Chlorophyll A levels (mg/m 3...PIER (P) and INLET (1) assemblages as a function of added copper (ppb)... 23 Figure 17. Trends in chlorophyll A levels (mg/m 3 ) of the PIER (P) and...E 10 P 5- J A S O N 0 J F M A M J 1978 1979Date Figure 7. Chlorophyll A levels (mg/m 3) of the phytoplank- ton assemblages taken from the PIER (P

Material for electrodes of low temperature plasma generators

DOEpatents

Caplan, Malcolm; Vinogradov, Sergel Evge'evich; Ribin, Valeri Vasil'evich; Shekalov, Valentin Ivanovich; Rutberg, Philip Grigor'evich; Safronov, Alexi Anatol'evich

2008-12-09

Material for electrodes of low temperature plasma generators. The material contains a porous metal matrix impregnated with a material emitting electrons. The material uses a mixture of copper and iron powders as a porous metal matrix and a Group IIIB metal component such as Y.sub.2O.sub.3 is used as a material emitting electrons at, for example, the proportion of the components, mass %: iron: 3-30; Y.sub.2O.sub.3:0.05-1; copper: the remainder. Copper provides a high level of heat conduction and electric conductance, iron decreases intensity of copper evaporation in the process of plasma creation providing increased strength and lifetime, Y.sub.2O.sub.3 provides decreasing of electronic work function and stability of arc burning. The material can be used for producing the electrodes of low temperature AC plasma generators used for destruction of liquid organic wastes, medical wastes, and municipal wastes as well as for decontamination of low level radioactive waste, the destruction of chemical weapons, warfare toxic agents, etc.

Material for electrodes of low temperature plasma generators

DOEpatents

Caplan, Malcolm; Vinogradov, Sergel Evge'evich; Ribin, Valeri Vasil'evich; Shekalov, Valentin Ivanovich; Rutberg, Philip Grigor'evich; Safronov, Alexi Anatol'evich; Shiryaev, Vasili Nikolaevich

2010-03-02

Material for electrodes of low temperature plasma generators. The material contains a porous metal matrix impregnated with a material emitting electrons. The material uses a mixture of copper and iron powders as a porous metal matrix and a Group IIIB metal component such as Y.sub.2O.sub.3 is used as a material emitting electrons at, for example, the proportion of the components, mass %: iron:3-30; Y.sub.2O.sub.3:0.05-1; copper: the remainder. Copper provides a high level of heat conduction and electric conductance, iron decreases intensity of copper evaporation in the process of plasma creation providing increased strength and lifetime, Y.sub.2O.sub.3 provides decreasing of electronic work function and stability of arc burning. The material can be used for producing the electrodes of low temperature AC plasma generators used for destruction of liquid organic wastes, medical wastes, municipal wastes as well as for decontamination of low level radioactive waste, the destruction of chemical weapons, warfare toxic agents, etc.

A Study of the Diffusion, Electrochemical Mobility and Removal of Dissolved Copper in a Saturated Porous Medium.

DTIC Science & Technology

1980-11-01

aqueous solutions : use of activity coefficients in transition-state models: Geochimica et Cosmochimica Acta, v...native state at 25°C at any activity level below 10+46.0 in an aqueous solution . Because such an activity level is impossible, sodium cannot be reduced...stoichiometric coefficients . It is necessary to calculqte the activity coefficients of dissolved copper in the test solutions in order to render an

Determination of silver, bismuth, cadmium, copper, lead, and zinc in geologic materials by atomic absorption spectrometry with tricaprylylmethylammonium chloride

USGS Publications Warehouse

Viets, J.G.

1978-01-01

Interferences commonly encountered in the determination of silver, bismuth, cadmium, copper, lead, and zinc at crustal abundance levels are effectively eliminated using a rapid, sensitive, organic extraction technique. A potassium chlorate-hydrochloric acid digestion solubilizes the metals not tightly bound in the silicate lattice of rocks, soils, and stream sediments. The six metals are selectively extracted into a 10% Aliquat 336-MIBK organic phase in the presence of ascorbic acid and potassium iodide. Metals in the organic extract are determined by flame atomic absorption spectrometry to the 0.02-ppm level for silver, cadmium, copper, and zinc and to the 0.2-ppm level for bismuth and lead with a maximum relative standard deviation of 18.8% for known reference samples. An additional hydrofluoric acid digestion may be used to determine metals substituted in the silicate lattice.

Results of a preimpoundment water-quality study of Swatara Creek, Pennsylvania

USGS Publications Warehouse

Fishel, David K.; Richardson, J.E.

1986-01-01

The impoundment will act as a sediment trap and thus reduce the concentrations of total phosphorus, iron, aluminum, lead, copper, and zinc immediately downstream from the impoundment. Large storm discharges and releases from the hypolimnion of the reservoir to attain the winter-pool level may contain low oxygen concentrations and elevated concentrations of iron, aluminum, lead, copper, and zinc. Unless conservation releases from the multi-level release gates are carefully controlled, low dissolved-oxygen levels and high metal concentrations may degrade the downstream water quality and be detrimental to the aquatic community.

Toxic responses of bivalves to metal mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathew, P.; Menon, N.R.

Although there is a growing body of information on the toxicity of individual heavy metals to economically important on the toxicity of individual heavy metals to economically important species of bivalves, literature on the lethal toxicity of metal mixtures to bivalves under controlled conditions is rather limited. In the present investigation the toxic effects of combinations of copper - mercury and copper - mercury and copper - cadmium at lethal levels of two marine bivalve species, Perna indica and Donax incarnatus, have been delineated.

Aortic sudanophilia an zinc-copper ratios in the liver of vervet monkeys fed different types of dietary fibre.

PubMed

Klevay, L M; Mendelsohn, D; Vanderwatt, J J; Davidson, L M; Kritchevsky, D

1981-04-18

Vervet monkeys (Cercopithecus aethiops pygerethrus) were fed a semipurified diet containing 40% sucrose, 25% casein, 14% hydrogenated coconut oil and 15% fibre for 6 months. Alfalfa, cellulose, or wheat straw was the source of the fibre. All the diets led to aortic sudanophilia, but the group fed wheat straw had the highest copper level in the liver and the least sudanophilia. The order to severity of the sudanophilia, the ratio of zinc to copper in the fibers, and the ratio of zinc to copper in the liver were: alfalfa-fed group greater than cellulose-fed group greater than wheat straw-fed group. These findings, which may have resulted from the relatively large amount of copper in the wheat straw, are consonant with observations on lipid metabolism in other species.

Measurements of copper ground-state and metastable level population densities in a copper-chloride laser

NASA Technical Reports Server (NTRS)

Nerheim, N. M.

1977-01-01

The population densities of both the ground and the 2D(5/2) metastable states of copper atoms in a double-pulsed copper-chloride laser are correlated with laser energy as a function of time after the dissociation current pulse. Time-resolved density variations of the ground and excited copper atoms were derived from measurements of optical absorption at 324.7 and 510.6 nm, respectively, over a wide range of operating conditions in laser tubes with diameters of 4 to 40 mm. The minimum delay between the two current pulses at which lasing was observed is shown to be a function of the initial density and subsequent decay of the metastable state. Similarly, the maximum delay is shown to be a function of the initial density and decay of the ground state.

Porphyry copper assessment of the Tibetan Plateau, China: Chapter F in Global mineral resource assessment

USGS Publications Warehouse

Ludington, Steve; Hammarstrom, Jane M.; Robinson, Gilpin R.; Mars, John L.; Miller, Robert J.

2012-01-01

Assessment results, presented in tables and graphs, show mean expected amounts of metal and rock in undiscovered deposits at different quantile levels, as well as the arithmetic mean for each tract. This assessment estimated a mean of 39 undiscovered porphyry copper deposits within the assessed permissive tracts on the Tibetan Plateau. This represents nearly four times the number of known deposits (11) already discovered. Predicted mean (arithmetic) resources that could be associated with the undiscovered deposits are about 145,000,000 t of copper and about 4,900 t of gold, as well as byproduct molybdenum and silver. Reliable reports of the identified resources in the 11 known deposits total about 27,000,000 t of copper and about 800 t of gold. Therefore, based on the assessments of undiscovered Tibetan Plateau resources in this report, about six times as much copper may occur in undiscovered porphyry copper deposits as has been identified to date.

Characterization of polycyclic aromatic hydrocarbons in soil close to secondary copper and aluminum smelters.

PubMed

Hu, Jicheng; Wu, Jing; Zha, Xiaoshuo; Yang, Chen; Hua, Ying; Wang, Ying; Jin, Jun

2017-04-01

A total of 35 surface soil samples around two secondary copper smelters and one secondary aluminum smelter were collected and analyzed for 16 USEPA priority polycyclic aromatic hydrocarbons (PAHs). The concentrations of PAHs were highest when the soil sample sites were closest to the secondary copper smelters. And, a level gradient of PAHs was observed in soil samples according to the distance from two secondary copper smelters, respectively. The results suggested that PAH concentrations in surrounding soils may be influenced by secondary copper smelters investigated, whereas no such gradient was observed in soils around the secondary aluminum smelter. Further analysis revealed that PAH patterns in soil samples also showed some difference between secondary copper and aluminum smelter, which may be attributed to the difference in their fuel and smelting process. PAH patterns and diagnostic ratios indicated that biomass burning may be also an important source of PAHs in the surrounding soil in addition to the emissions from the plants investigated.

The Hugoniot adiabat of crystalline copper based on molecular dynamics simulation and semiempirical equation of state

NASA Astrophysics Data System (ADS)

Gubin, S. A.; Maklashova, I. V.; Mel'nikov, I. N.

2018-01-01

The molecular dynamics (MD) method was used for prediction of properties of copper under shock-wave compression and clarification of the melting region of crystal copper. The embedded atom potential was used for the interatomic interaction. Parameters of Hugonoit adiabats of solid and liquid phases of copper calculated by the semiempirical Grüneisen equation of state are consistent with the results of MD simulations and experimental data. MD simulation allows to visualize the structure of cooper on the atomistic level. The analysis of the radial distribution function and the standard deviation by MD modeling allows to predict the melting area behind the shock wave front. These MD simulation data are required to verify the wide-range equation of state of metals. The melting parameters of copper based on MD simulations and semiempirical equations of state are consistent with experimental and theoretical data, including the region of the melting point of copper.

25 years of HBM in the Czech Republic.

PubMed

Černá, Milena; Puklová, Vladimíra; Hanzlíková, Lenka; Sochorová, Lenka; Kubínová, Růžena

2017-03-01

Since 1991 a human biomonitoring network has been established in the Czech Republic as part of the Environmental Health Monitoring System, which was set out by the Government Resolution. During the last quarter-century, important data was obtained to characterize exposure to both children and adult populations to significant toxic substances from the environment, to development trends over time, to establish reference values and compare them with existing health-related values. Moreover, the saturation of population with several essential substances as selenium, zinc, copper or iodine has also been monitored. Development of analytical and statistical methods led to increase the capacity building, improvement of QA/QC in analytical laboratories and interpretation of results. The obtained results are translated to policy actions and are used in health risk assessment processes at local and national levels. Copyright © 2016 Elsevier GmbH. All rights reserved.

Copper tolerance mediated by polyphosphate degradation and low-affinity inorganic phosphate transport system in Escherichia coli.

PubMed

Grillo-Puertas, Mariana; Schurig-Briccio, Lici Ariane; Rodríguez-Montelongo, Luisa; Rintoul, María Regina; Rapisarda, Viviana Andrea

2014-03-19

Metal tolerance in bacteria has been related to polyP in a model in which heavy metals stimulate the polymer hydrolysis, forming metal-phosphate complexes that are exported. As previously described in our laboratory, Escherichia coli cells grown in media containing a phosphate concentration >37 mM maintained an unusually high polyphosphate (polyP) level in stationary phase. The aim of the present work was to evaluate the influence of polyP levels as the involvement of low-affinity inorganic phosphate transport (Pit) system in E. coli copper tolerance. PolyP levels were modulated by the media phosphate concentration and/or using mutants in polyP metabolism. Stationary phase wild-type cells grown in high phosphate medium were significantly more tolerant to copper than those grown in sufficient phosphate medium. Copper addition to tolerant cells induced polyP degradation by PPX (an exopolyphosphatase), phosphate efflux and membrane polarization. ppk-ppx- (unable to synthesize/degrade polyP), ppx- (unable to degrade polyP) and Pit system mutants were highly sensitive to metal even in high phosphate media. In exponential phase, CopA and polyP-Pit system would act simultaneously to detoxify the metal or one could be sufficient to safeguard the absence of the other. Our results support a mechanism for copper detoxification in exponential and stationary phases of E. coli, involving Pit system and degradation of polyP. Data reflect the importance of the environmental phosphate concentration in the regulation of the microbial physiological state.

Factorial design optimization of experimental variables in the on-line separation/preconcentration of copper in water samples using solid phase extraction and ICP-OES determination.

PubMed

Escudero, Luis A; Cerutti, S; Olsina, R A; Salonia, J A; Gasquez, J A

2010-11-15

An on-line preconcentration procedure using solid phase extraction (SPE) for the determination of copper in different water samples by inductively coupled plasma optical emission spectrometry (ICP-OES) is proposed. The copper was retained on a minicolumn filled with ethyl vinyl acetate (EVA) at pH 8.0 without using any complexing reagent. The experimental optimization step was performed using a two-level full factorial design. The results showed that pH, sample loading flow rate, and their interaction (at the tested levels) were statistically significant. In order to determine the best conditions for preconcentration and determination of copper, a final optimization of the significant factors was carried out using a central composite design (CCD). The calibration graph was linear with a regression coefficient of 0.995 at levels near the detection limit up to at least 300 μg L(-1). An enrichment factor (EF) of 54 with a preconcentration time of 187.5 s was obtained. The limit of detection (3σ) was 0.26 μg L(-1). The sampling frequency for the developed methodology was about 15 samples/h. The relative standard deviation (RSD) for six replicates containing 50 μg L(-1) of copper was 3.76%. The methodology was successfully applied to the determination of Cu in tap, mineral, river water samples, and in a certified VKI standard reference material. Copyright © 2010 Elsevier B.V. All rights reserved.

Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

PubMed Central

Stepien, Magdalena; Hughes, David J; Hybsier, Sandra; Bamia, Christina; Tjønneland, Anne; Overvad, Kim; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie-Christine; Katzke, Verena; Kühn, Tilman; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Orfanos, Phlippos; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Ricceri, Fulvio; Panico, Salvatore; Bueno-de-Mesquita, H B(as); Peeters, Petra H; Weiderpass, Elisabete; Lasheras, Cristina; Bonet Bonet, Catalina; Molina-Portillo, Elena; Dorronsoro, Miren; Huerta, José María; Barricarte, Aurelio; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Shungin, Dmitry; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Freisling, Heinz; Cross, Amanda J; Schomburg, Lutz; Jenab, Mazda

2017-01-01

Background: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers. Methods: A nested case–control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk. Results: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13–0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45–2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41–15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed. Conclusions: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings. PMID:28152549

CCS and SOD1 mRNA are reduced after copper supplementation in peripheral mononuclear cells of individuals with high serum ceruloplasmin concentration.

PubMed

Suazo, Miriam; Olivares, Felipe; Mendez, Marco A; Pulgar, Rodrigo; Prohaska, Joseph R; Arredondo, Miguel; Pizarro, Fernando; Olivares, Manuel; Araya, Magdalena; González, Mauricio

2008-04-01

The limits of copper homeostatic regulation in humans are not known, making it difficult to define the milder effects of early copper excess. Furthermore, a robust assay to facilitate the detection of early stages of copper excess is needed. To address these issues, we assessed changes in relative mRNA abundance of methallothionein 2A (MT2A), prion (PrP), amyloid precursor-like protein 2 (APLP2), Cu/Zn superoxide dismutase (SOD1) and its copper chaperone (CCS) in peripheral mononuclear cells (PMNCs) from healthy adults representing the 5% highest and lowest extremes in the distribution curve of serum ceruloplasmin (Cp) concentrations of 800 individuals. The intracellular Cu content was also determined. PMNCs were isolated from individuals before and after exposure to a single daily dose of 10 mg Cu (as CuSO(4)) for 2 months. Results showed that although there were fluctuations in serum Cp values of the samples assessed before copper exposure, no significant differences were observed in cell copper content or in the relative abundance of MT2A, PrP and APLP2 transcripts in PMNCs. Also, these values were not modified after copper supplementation. However, CCS and SOD1 mRNA levels were reduced in PMNCs after copper supplementation in the individuals with the high Cp values, suggesting that they should be further explored as biomarkers of moderate copper overload in humans.

Earth's copper resources estimated from tectonic diffusion of porphyry copper deposits

NASA Astrophysics Data System (ADS)

Kesler, Stephen E.; Wilkinson, Bruce H.

2008-03-01

Improved estimates of global mineral endowments are relevantto issues ranging from strategic planning to global geochemicalcycling. We have used a time-space model for the tectonic migrationof porphyry copper deposits vertically through the crust tocalculate Earth's endowment of copper in mineral deposits. Themodel relies only on knowledge of numbers and ages of porphyrycopper deposits, Earth's most widespread and important sourceof copper, in order to estimate numbers of eroded and preserveddeposits in the crust. Model results indicate that 125,895 porphyrycopper deposits were formed during Phanerozoic time, that only47,789 of these remain at various crustal depths, and that thesecontain 1.7 x 1011 tonnes (t) of copper. Assuming that othertypes of copper deposits behave similarly in the crust and haveabundances proportional to their current global production yieldsan estimate of 3 x 1011 t for total global copper resourcesat all levels in Earth's crust. Thus, 0.25% of the copper inthe crust has been concentrated into deposits through Phanerozoictime, and about two-thirds of this has been recycled by upliftand erosion. The amount of copper in deposits above 3.3 km,a likely limit of future mining, could supply current worldmine production for 5500 yr, thus quantifying the highly unusualand nonrenewable nature of mineral deposits.