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Kaden D.,Free University of Berlin | Bush A.I.,University of Melbourne | Danzeisen R.,International Copper Association | Bayer T.A.,University of Gottingen | Multhaup G.,Free University of Berlin
International Journal of Alzheimer's Disease | Year: 2011

Recent data from in vitro, animal, and human studies have shed new light on the positive roles of copper in many aspects of AD. Copper promotes the non-amyloidogenic processing of APP and thereby lowers the Aβ production in cell culture systems, and it increases lifetime and decreases soluble amyloid production in APP transgenic mice. In a clinical trial with Alzheimer patients, the decline of Aβ levels in CSF, which is a diagnostic marker, is diminished in the verum group (8mg copper/day), indicating a beneficial effect of the copper treatment. These observations are in line with the benefit of treatment with compounds aimed at normalizing metal levels in the brain, such as PBT2. The data reviewed here demonstrate that there is an apparent disturbance in metal homeostasis in AD. More research is urgently needed to understand how this disturbance can be addressed therapeutically. Copyright © 2011 Daniela Kaden et al. Source

Miller F.J.,Fred J. Miller and LLC | Kaczmar S.W.,OBrien and Gere Engineers Inc. | Danzeisen R.,International Copper Association | Moss O.R.,Owen Moss Advisors
Inhalation Toxicology | Year: 2013

Workplace air is monitored for overall dust levels and for specific components of the dust to determine compliance with occupational and workplace standards established by regulatory bodies for worker health protection. Exposure monitoring studies were conducted by the International Copper Association (ICA) at various industrial facilities around the world working with copper. Individual cascade impactor stages were weighed to determine the total amount of dust collected on the stage, and then the amounts of soluble and insoluble copper and other metals on each stage were determined; speciation was not determined. Filter samples were also collected for scanning electron microscope analysis. Retrospectively, there was an interest in obtaining estimates of alveolar lung burdens of copper in workers engaged in tasks requiring different levels of exertion as reflected by their minute ventilation. However, mechanistic lung dosimetry models estimate alveolar lung burdens based on particle Stokés diameter. In order to use these dosimetry models the mass-based, aerodynamic diameter distribution (which was measured) had to be transformed into a distribution of Stokés diameters, requiring an estimation be made of individual particle density. This density value was estimated by using cascade impactor data together with scanning electron microscopy data from filter samples. The developed method was applied to ICA monitoring data sets and then the multiple path particle dosimetry (MPPD) model was used to determine the copper alveolar lung burdens for workers with different functional residual capacities engaged in activities requiring a range of minute ventilation levels. © 2013 Informa Healthcare USA, Inc. All rights reserved. Source

Meek M.E.,University of Ottawa | Levy L.S.,Cranfield University | Beck B.D.,Gradient Corporation | Danzeisen R.,International Copper Association | And 3 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2010

This article addresses the content of the workshop, including a panel discussion relevant to delineation of a path forward in relation to risk assessment of essential metals. The state of the art of risk assessment and associated issues for essential metals are outlined initially, followed by brief illustration by the case studies considered at the workshop (i.e., copper, zinc, and manganese). Approaches for the future testing strategies of essential metals are discussed in terms of options to increase efficiency and accuracy of assessments. Subsequently, recommendations for pragmatic next steps to advance progress and facilitate uptake by the regulatory risk assessment community are presented. Source

Chen H.,University of California at Berkeley | Chen H.,Nanjing University | Attieh Z.K.,University of California at Berkeley | Attieh Z.K.,American University of Science and Technology | And 15 more authors.
Journal of Nutrition | Year: 2010

We previously detected a membrane-bound, copper-containing oxidase that may be involved in iron efflux in BeWo cells, a human placental cell line. We have now identified a gene encoding a predicted multicopper ferroxidase (MCF) with a putative C-terminal membrane-spanning sequence and high sequence identity to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate MCF. Molecular modeling revealed conservation of all type I, II, and III copper-binding sites as well as a putative iron-binding site. Protein expression was observed in multiple diverse mouse tissues, including placenta and mammary gland, and the expression pattern was distinct from that of Cp and Heph. The protein possessed ferroxidase activity, and protein levels decreased in cellular copper deficiency. Knockdown with small interfering RNA in BeWo cells indicates that this gene represents the previously detected oxidase. We propose calling this new member of the MCF family "zyklopen." © 2010 American Society for Nutrition. Source

Van Genderen E.,ZINC Inc | Adams W.,Rio Tinto Alcan | Dwyer R.,International Copper Association | Garman E.,Nickel Producers Environmental Research Association | Gorsuch J.,Copper Development Association Inc
Environmental Toxicology and Chemistry | Year: 2015

The fate and biological effects of chemical mixtures in the environment are receiving increased attention from the scientific and regulatory communities. Understanding the behavior and toxicity of metal mixtures poses unique challenges for incorporating metal-specific concepts and approaches, such as bioavailability and metal speciation, in multiple-metal exposures. To avoid the use of oversimplified approaches to assess the toxicity of metal mixtures, a collaborative 2-yr research project and multistakeholder group workshop were conducted to examine and evaluate available higher-tiered chemical speciation-based metal mixtures modeling approaches. The Metal Mixture Modeling Evaluation project and workshop achieved 3 important objectives related to modeling and interpretation of biological effects of metal mixtures: 1) bioavailability models calibrated for single-metal exposures can be integrated to assess mixture scenarios; 2) the available modeling approaches perform consistently well for various metal combinations, organisms, and endpoints; and 3) several technical advancements have been identified that should be incorporated into speciation models and environmental risk assessments for metals. © 2015 SETAC. Source

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