SYMPOSIUM DESCRIPTION

Plenary Session 1: Distinguished Scientists of the World

Chair: Jeanne Freeland-Graves

Responsiveness of Zinc Transporters to Dietary Zinc, in Mice and Humans

Robert Cousins, PhD

Dr. Cousins, Boston Family Professor of Nutrition, University of Florida, USA, and Member, USA National Academy of Sciences, is highly regarded on an international basis for his expertise in zinc transport. The 24 zinc transporters are from two families, ZnT and ZIP, and these control zinc acquisition, homeostasis and function. Specific ZnTs and ZIPs expressed in leukocytes and reticulocytes of humans respond to a restriction in dietary zinc intake. Similarly, normal and mutant mice with deletions of specific zinc transporter genes show altered patterns of zinc metabolism in response to dietary zinc. A review of the zinc transporter field and perspectives will emphasize how this new information is important for policy decisions about requirements, and it will provide an understanding of the role of this micronutrient in cell metabolism.

Plenary Session 2: Distinguished Scientists of the World

Chair: Ole Andersen

Copper and Zinc in Alzheimer's Disease:

Cognitive Loss from Ingestion of Inorganic Copper

George Brewer, MD

Dr. Brewer, Morton S. and Henrietta K. Sellner Emeritus Professor, Human Genetics and Emeritus Professor of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA, has worked for many years on copper, zinc, and molybdenum metabolism. He developed zinc as a therapy for Wilson's disease, which was approved by the Food and Drug Administration based on his data in 1997. He has made recent contributions which have advanced the knowledge of copper and zinc status and metabolism in Alzheimer's disease. This presentation results from an epiphany of understanding of the role of ingestion of inorganic copper on cognitive loss and its contributions to the current epidemic of Alzheimer's disease.

Plenary Session 3: New Development in Iron Metabolism and its Disorders

Chairs: Prem Ponka and Gregory J Anderson

Iron Absorption

Gregory J Anderson, PhD

Dr. Anderson, Professor and Head, Iron Metabolism Laboratory, Queensland Institute of Medical Research, Brisbane, Australia, studies the molecular basis of iron homeostasis and diseases associated with disturbances in iron metabolism. He will consider the mechanisms and regulation of intestinal iron transport and discuss recent advances in this area. There will be a particular focus on the role of iron oxidases in iron absorption and how the mechanisms of iron transport by the gut vary with age.

Erythroid Cells and Macrophages: Major Players in Iron Metabolism

Prem Ponka, MD, PhD

Dr. Ponka, Professor, Physiology and Medicine, McGill University, Montreal, Quebec, Canada, investigates regulation of iron balance in the body and cells, and how dysregulated iron homeostasis produces disease. The major pathways of iron involve the movement from plasma transferrin to hemoglobin in developing red blood cells, and the release of iron from macrophages that recycle hemoglobin iron of senescent erythrocytes. Specifically, he will address molecular mechanisms of these processes.

Inherited Disorders of Iron Metabolism

Carole Beaumont, PhD

Dr. Beaumont, INSERM Director of Research, Bichat-Beaujon Biomedical Research Center, Medical Faculty of the University of Paris Diderot, France, studies iron and heme synthesis from the point of view of genetics, physiology and pathophysiology. She will discuss genetically-based disorders of iron metabolism in mammals and their phenotypic manifestations.

Iron Sequestration and Anemia of Inflammation

Tomas Ganz, MD, PhD

Dr. Ganz, Professor, Medicine and Pathology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA, has a long-term interest in the interface between innate immunity and iron metabolism. His studies on antimicrobial peptides of phagocytes and epithelia led to his discovery of hepcidin. Subsequent research has revealed that hepcidin is a key regulator of organismal iron homeostasis. He will discuss the role of hepcidin in iron sequestration, iron-limited erythropoiesis and anemia of inflammation.

Iron and Atherosclerosis

Elizabeta Nemeth, PhD

Dr. Nemeth, Associate Professor, Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA, is interested in iron metabolism and its disorders, focusing on the mechanism of hepcidin dysregulation in iron overload diseases and inflammatory disorders. She will discuss results supporting the hypothesis that hepcidin-mediated sequestration of iron in plaque macrophages promotes atherosclerosis.

Background: Iron is essential for oxidation-reduction catalysis and bioenergetics, but unless appropriately shielded, this metal plays a key role in the formation of toxic oxygen radicals that can attack all biological molecules. Hence, specialized molecules for the acquisition, transport, and storage of iron in a soluble nontoxic form have evolved. This symposium will discuss recently discovered players in cellular and organismal iron homeostasis and how defects or dysregulation during pathological conditions causes iron deficiency or overload.

Plenary Session 4: Fifty Years of Discovery of the Miracle Element Zinc ISTERH -11 acknowledge the generous support from Labcatal

Chairs: Ananda Prasad and George Brewer

Zinc Deficiency

Ananda Prasad, MD, PhD

Dr. Prasad, Distinguished Professor of Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA, discovered the role of zinc in humans in the early sixties. This led to the establishment of a recommended dietary allowance for zinc in humans in 1974. He has continued active and productive research in this area for the past 50 years. In this plenary session he will discuss recent discoveries regarding roles for zinc in immunity and inflammation.

Zinc Status: Relation to Nutrition in Pregnant, Turkish Women and Association with Neural Tube Defects in Children

Ayhan Cavdar, MD

Dr. Cavdar, Professor, Pediatrics and Hematology-Oncology, Ankara University School of Medicine, Ankara, Turkey, has been involved in active research in the field of zinc metabolism for over four decades. She is greatly respected for her scientific contributions and was appointed as the first President, and now, Honorary Member, of the Turkish Academy of Sciences. Her presentation in this plenary session will focus on the importance of zinc nutriture during pregnancy and its consequence on children.

Effect of Dietary Zinc on Brain Development and Function

Harold Sandstead, MD

Dr. Sandstead, Professor Emeritus, Preventive Medicine, University of Texas Medical Branch, Galveston, Texas, USA, started his research in the field of zinc metabolism in 1961 in collaboration with Dr. Prasad at NAMRU-3, Egypt. He has been a key contributor in the development of research in this field and will present effects of zinc on development and psychological performance.

Zinc Therapy for Wilsons Disease and Alzheimers Disease

George Brewer, MD

Dr. Brewer, Morton S. and Henrietta K. Sellner Emeritus Professor of Human Genetics, University of Michigan, USA. The development of zinc as a therapy for Wilsons disease by Dr. Brewer is truly a great therapeutic achievement for a fatal genetic disorder. In families known to carry the gene for this disease, the susceptible patients may never suffer from liver or brain damage due to copper excess if zinc therapy as a preventive agent is started promptly. His contributions in the area of zinc therapy for Wilsons disease will be highlighted.

The Role of Zinc in Child Health and Survival

Robert Black, MD, MPH

Dr. Black, Professor, Johns Hopkins Bloomberg School of Public Health, Maryland, USA, and his colleagues have been instrumental in developing zinc as a therapeutic agent for treatment of acute diarrhea in children. This has resulted in a remarkable decrease in mortality from 85% to 15%. This therapeutic achievement in Africa led to an article in TIME magazine, December 2009, and the reporter labeled zinc as a Miracle element. He will describe important roles for zinc in the treatment of childhood diarrhea and pneumonia.

Background: Zinc deficiency is now known to affect nearly two billion people in developing countries. The widespread growth retardation that is observed in these countries is related primarily to a deficiency of zinc. Millions of children are now surviving acute diarrhea and pneumonia because of zinc supplementation. Zinc therapy also is preventing blindness in millions of elderly with AMD in the world. The overwhelming impact of the remarkable effectiveness of zinc therapy in humans will be covered in these presentations.

Plenary Session 5: Cancer Promotion and Prevention by Trace Elements

NTES / ISTERH -11 acknowledge the generous support from Pharma Nord AS and from Yara International ASA

Chairs: Jan Alexander and Jan Aaseth

Selenium Intervention Does it Act as an Anticarcinogenic?

Antti Aro, MD, PhD

Dr. Aro, Professor Emeritus, National Institute for Health and Welfare, Finland, will discuss the effects of selenium-enriched fertilization on health in Finland, a low-selenium country.

Risk Assessment of Arsenic in Food and Drinking Water

Jan Alexander, MD, PhD

Dr. Alexander, Professor, Environmental Toxicology, National Institute of Public Health, Norway, has conducted a number of investigations on interactions between selenium and arsenic. He will discuss the evaluation of risk assessments of arsenic exposure.

Selenium and Cancer Prevention: Observations and Hypotheses

Eystein Glattre, MD Jan Alexander, MD, PhD and Jan Aaseth, MD, PhD

Dr. Glattre, retired Research Leader, Norwegian Cancer Registry, University of Oslo, Norway, in collaboration with Drs. Aaseth and Alexander, will present studies on the anticarcinogenic action of some selenium species, focusing on malignancies in the thyroid. These will explain a protective role of selenium metabolites.

The 100 Year Old Anti-Cancer Drug Selenium

Olav Christophers, PhD, Anna Haug, PhD, Jan Aaseth, MD, PhD and Graham Lyons, PhD

Drs. Christophersen, Haug, Aaseth and Lyons are a research group that has collaborated at the University for Life Sciences, Norway. They will discuss selenium as a potential cytostatic agent in malignant diseases, especially prostatic and mammary cancers resistant to traditional agents.Justification is provided for using appropriate selenite doses in a combination regimen.

Background: A large number of studies have explored the possible anti-carcinogenic potential of selenium compounds. These include animal studies, and epidemiological and interventional studies in humans. The present symposium aims to elucidate the interaction between carcinogenic elements such as arsenic and other mechanisms of the presumed protective effect of selenium.

Symposium A: Manganese (Mn) and Its Neurotoxic and Neurobehavioral Effects

Chairs: Michael Aschner and Brad Racette

C. Elegans and the Role of Dopamine in Manganese-Induced Neurodegeneration

Michael Aschner, PhD

Dr. Aschner, Professor, Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA, has studied mechanisms of manganese (Mn) transport into the brain and has identified molecular mechanisms associated with its toxicity, focusing on the role of reactive oxygen species in mediating dopaminergic neurodegeneration.

Imaging Biomarkers of Mn-Associated Neurotoxicity in Shipyard Workers

Brad Racette, MD

Dr. Racette, Professor, Neurology, Washington University, St. Louis, Missouri, USA, focuses on the environmental epidemiology of Parkinsons disease. He has conducted a large epidemiology study of parkinsonism in shipyard welders, demonstrating that healthy, active welders have dysfunction of the dopamine system and connections between caudate and putamen, and selected cortical and subcortical pathways. These studies suggest that Mn-exposed workers demonstrate a unique pattern of neurotoxicity that could potentially be used to identify workers prior to onset of symptoms.

Performance Alterations Associated with Occupational Exposure to Mn--a Meta-Analysis

Monika Meyer-Baron, PhD

Dr. Meyer-Baron, Professor, Leibniz-Institut fr Arbeitsforschung, Dortmund, Germany, will review evidence of performance effects that result from occupational exposure to Mn. She will discuss a meta-analytical method of effect size estimates addressing: (1) identification of affected functions; (2) identification of sensitive neuropsychological tests; and (3) analyses of exposure-effect relationships.

Manganese Neurotoxicity in Welders

Dag G Ellingsen, MD, PhD

Dr. Ellingsen, Head, Chemical and Biological Work Environment, National Institute of Occupational Health, Oslo, Norway, has carried out epidemiological studies on the neurotoxic effects of Mn in the Mn alloy producing industry, and among welders. A recent follow-up study of Russian welders will be presented.

An Integrated Biomarker for Manganese (Mn) Exposure and Toxicity

Wei Zheng, PhD

Dr. Wei Zheng, Professor and Head, School of Health Sciences, Purdue University, West Lafayette, USA, has focused his research on Mn-Fe interaction in animal models and human cohorts. The finding on the opposite trend in systemic Mn and Fe variations in smelting workers has led to a new concept of the Integrated Biomarker for Mn exposure and neurotoxicity assessment.

Background: Environmental or occupational exposure to Mn causes a neurologic dysfunction resembling idiopathic Parkinsons disease (PD). This is characterized by motor deficits and damage to basal ganglia, with dopamine (DA) contributing to these disorders. The purpose is to provide a state-of-the-art update on recent findings, ranging from genetic and molecular studies in animal models to studies in humans exposed to Mn at the work place. This session will highlight the importance of exposure paradigms and gender to outcome, and provide insight into current methods for imaging the sequelae of Mn exposure.

Symposium B: Priority of Micronutrients in Achieving Millennium Development Goals (MDGs) 4

Chair: SK Roy

Priority of Micronutrients in Achieving MDGs

SK Roy, PhD

Dr. S.K. Roy, Senior Scientist, International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh has been a pioneer in testing the efficacy of zinc in reducing childhood diarrhea, shigellosis, and cholera. He has demonstrated ultra structural changes regulating electrolyte and water transport in zinc deficiency models, and documented a role of zinc deficiency in malnutrition. Results of trials in cholera patients create new advancements for clinical nutrition and public health.

Plasma Nutriproteomics to Assess Micronutrient Deficiencies

Keith P West, PhD

Dr. West, Professor, Nutrition, School of Public Health, Johns Hopkins University, Maryland, USA, has been a leader in Vitamin A research and reducing maternal mortality in large scale studies. He will present new findings of reducing neonatal mortality with supplementation of the newborn, and interactions of micronutrients with plasma proteins as biomarkers.

Effects of Prenatal and Perinatal Micronutrient Supplementation on the Immune Function of Children

Rubhana Raqib, PhD

Dr. Raqib, Head, Nutritional Biochemistry Laboratory, ICDDRB, Dhaka, Bangladesh, has obtained the first patent for ICDDR on detection of tuberculosis. She has worked on effects of zinc supplementation on immunological responses in patients with dysentery and acute watery diarrhea. Her current work includes studying the effects of zinc and micronutrient supplementation prenatally on development of innate and vaccine specific immune responses in offspring (both human and animal models).

Improving Maternal and Child Health by Combating Iodine Deficiency Disorders

Umesh Kapil, PhD

Dr. Kapil, Professor and Head, Nutrition, All India Institute of India, Ansari Nagar, New Delhi, India, will speak on the iodine deficiency disorders (IDD) scenario in India that is present throughout the country. Out of 342 districts surveyed by the government of India, 285 have been found to be endemic for IDD. The government is implementing a policy of universal salt iodization since 1984, 100-200 g/l. The survey results indicate that India is progressing towards elimination of IDD. The iodine status of Indian children and its relationship with malnutrition and child mortality will be discussed.

Pediatric Iron Deficiency: Strategies to Prevent Loss of Developmental Potential

Maureen Black, PhD

Dr. Black, Professor, Pediatrics, University of Maryland School of Medicine, USA, will discussthe impact of iron deficiency during infancy on childrens life course development. She also will reviewiron deficiency prevention trials and strategies to reduce the negative effects of iron deficiency on child development.

Background: Reducing mortality in under-five children is the millennium development goal 4 (MDG 4). It is highly dependent on child nutritional status, infection and micronutrient trace element status. The symposium will provide international evidence and a critical evaluation of the influence of micronutrients such as zinc, iron, selenium, iodine, vitamin A and micronutrients across the life cycle for modifying the effects on reduction of child mortality. An understanding of the role of the micronutrients in child mortality will set a higher priority in global policy and strategy, facilitating an achievement of MDG 4.

Symposium C: Health Effects of Low-Dose Exposure to Toxic Metals

ICOH, ISTERH, Scientific Committee on the Toxicology of Metals (SCTM). International Commission on Occupational Health (SCTM/ICOH), and Scientific Committee Neurotoxicology and Psychophysiology (SCNP)/

Chair: Monica Nordberg

Diabetics - a Vulnerable Group at Exposure to Toxic Metals

Lars Barregard, MD, PhD

Dr. Barregard, Professor and Chief Physician, Occupational and Environmental Medicine, Sahlgrenska University Hospital, Norway, and Chair, SCTM/ICOH, has made important contributions regarding the influence of metals on kidney disease and has identified diabetic subjects as a sensitive group to exposure to cadmium.

Kidney Dysfunction and Cadmium Exposure Factors Influencing Dose-Response Relationship

Gunnar Nordberg, MD, PhD

Dr. Nordberg, Professor Emeritus, University of Umea, Sweden, has almost 50 years of experience and contributions to metal toxicology. He will discuss the role of cadmium in kidney dysfunction.

Kidney Disease and Diabetes due to Low-Level Cadmium and Lead Exposure

Ingvar A Bergdahl, PhD

Dr. Bergdahl, Associate Professor, Umea University, Sweden, is the Deputy Coordinator of the EU project PHIME. His work focuses on the health effects of lead and cadmium in humans. He conducts case-control studies in the Northern Sweden Health and Disease Study, in which prospectively-collected blood samples are used for biological monitoring of exposure.

Parkinsonism Effects from Lifetime Manganese Exposure

Roberto Lucchini, MD, PhD

Dr. Lucchini, Professor, Occupational Health, University of Brescia, Italy, and Chair, SCNP/ICOH, has centered his research on the toxicity of manganese and lead. His newest area will be the effect on cognitive and motor development in children.

Risk Assessment for Cadmium - Time for a Change of Paradigm?

Staffan Skerfving, MD, PhD

Dr. Skerfving, Professor Emeritus, Occupational and Environmental Medicine, University Hospital, Lund, Sweden and Coordinator, European Union Public Health Impact of Mixed Elements exposure, has almost 50 years of experience in metal toxicology and its related health effects. He will discuss the risk of low dose exposures to metals.

Background: The use of improved scientific methods for assessment of exposure and biological effects has shown adverse health effects of toxic metals at low doses, at levels previously assumed to be safe. This is true for lead (neurotoxicity/nephrotoxicity), mercury (neurotoxicity), manganese (neurotoxicity), and cadmium (nephrotoxicity/toxic effects on the skeleton). Emerging evidence suggests that low dose exposure to several toxic metals is associated with cardiovascular effects and increased risks for cancer and diabetes.

Symposium D: Indispensable Element of Our Lives: Boron

Chair: Sukru Ozturk

BOREN and Boron

Sukru Ozturk, PhD

Dr. Ozturk, President, National Boron Research Institute (BOREN). BOREN aims to increase consumption of boron products in Turkey and to develop and support studies for potential new sources. Another scope of the Institute is to form a databank and documentation center for individuals interested in boron products. He supervises all the studies to be discussed in this plenary session.

Exposure Assessment of Boron in an Acid Plant in Turkey

Yalcin Duydu, PhD

Dr. Duydu, Professor, Pharmaceutical Toxicology, Faculty of Pharmacy, Ankara University, Turkey, will discuss the role of boron on human reproduction.

Reproductive Toxicity in Boron Exposed Workers in Turkey

Nursen Basaran, PhD

Dr. Basaran, Professor, Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey, will discuss studies on the reproductive effects of boron.

Reconciliation of Human and Experimental Reproductive Toxicity Data on Boric Acid/Borates

Hermann M. Bolt, PhD

Dr. Bolt, Emeritus Professor, Leibniz Research Centre for Working Environment and Human Factors, Germany has expertise in boron toxicity.

Dietary Boron: Progress in Establishing Essential Roles in Human Physiology

Curtiss Hunt, PhD

Dr. Hunt, retired scientist, Vienna, has been affiliated with the USDA ARS Grand Forks Human Nutrition Research Center and the University of North Dakota. USA. His work has centered on trace element nutrition, primarily with boron and copper.

Background: Boron is one of the essential elements for human life. The purpose of this symposium is to discuss the importance of boron in our lives with the help of leaders in the field.

Symposium E: Challenges in Treatment of Disorders of Copper Metabolism

Chairs: Hiroko Kodama and Norikazu Shimizu

Treatment of Patients with Neurologic Wilsons Disease

Norikazu Shimizu, MD, PhD

Dr. Shimizu, Assistant Professor, Toho University School of Medicine, Tokyo, Japan, sees patients with Wilsons disease. He has made important contributions in the treatment of these patients, especially for those with neurologic symptoms of the disease. Neurologic symptoms often become worse after treatment with chelating agents. He will discuss the potential mechanism and methods to prevent deterioration.

Early Signs at Birth or in the Neonatal Period before Typical Symptomatic Onset of Menkes Disease

Yan-Hong Gu, MD, PhD

Dr. Gu, Senior Investigator, Health Policy, National Research Institute for Child Healthand Development, Tokyo, Japan, has conducted biochemical and histochemical studies on the livers of patients with Wilsons disease. She will discuss the risk of hepatocellular carcinoma in patients with Wilsons disease who experience longer survival.

Combination Therapy with Injections of Copper and Oral Administrations of Disulfiram in the Macular Mouse, an Animal Model of Menkes Disease

Hiroko Kodama, MD, PhD

Dr. Kodama, Professor, Teikyo University School of Medicine, Tokyo, Japan, has proposed a novel combination treatment with injections of copper and oral administrations of disulfiram for patients with Menkes disease. She has been involved in studying the effects of the combination therapy in the macular mouse, an animal model of Menkes disease, and will discuss the mechanism, efficacy and adverse effects of this treatment.

A Novel Treatment of Menkes Disease and Occipital Horn Syndrome

Eishin Ogawa, MD, PhD

Dr. Ogawa, Assistant Professor, Teikyo University School of Medicine, Tokyo, Japan, is providing medical care to patients with Menkes disease and with occipital horn syndrome. He is using a combination therapy of injections with copper-histidine and oral administration of disulfiram. The efficacy and adverse effects of the treatments in these patients will be reported.

Background: Wilsons disease (WD), Menkes disease (MD) and occipital horn syndrome (OHS) are genetic disorders of copper metabolism. WD is characterized by copper toxicity, as presumably is AD. Chelating agents and zinc are effective for the treatment of WD. However, patients with neurologic WD show poor response to these treatments. In addition, the neurologic symptoms become temporarily worse just after treatment with chelating agents, causing serious problems in these patients. Moreover, patients with Wilsons disease may have a risk of hepatocellular carcinoma despite receiving treatment. These problems in patients with neurologic WD will be discussed in this symposium. MD and OHS are characterized by a copper deficiency, with the current-standard-ofcare being parenteral administrations of copper-histidine. However, the treatment is less effective for neurologic and connective tissue disorders. A novel treatment for MD and OHS will be discussed in this symposium. Finally, the role of copper in AD and the potential for the free form as a marker for the disease will be discussed.

Symposium F: Iron Physiology, Pathology, and Requirements

Chairs: James McClung and Ismail Cakmak

Iron and Zinc Malnutrition: A Neglected Health Issue in Developing Countries

Ismail Cakmak, PhD

Dr. Cakmak, Director, Global HarvestPlus Zinc Fertilizer Project, and Professor, Sabanci University, Istanbul, Turkey, has expertise on the impact of insufficient iron and zinc nutrition in developing countries. He will describe the effects of these trace elements on human health.

Iron Transport and Regulation of ZIP Metal-Ion Transport Proteins

Mitchell Knutson, PhD

Dr. Knutson, Associate Professor of Nutritional Biochemistry, Food Science and Human Nutrition Department, University of Florida, Gainesville, Florida, USA, investigates the molecular and cell biology of iron metabolism.

Nutritional Countermeasures for the Prevention of Diminished Iron Status

in the Female Athlete

James McClung, PhD

Dr. McClung, Nutrition Biologist, Military Nutrition Division, United States Army Research Institute of Environmental Medicine Natick, Massachusetts, USA,investigates the impact of iron deficiency on bone health and skeletal muscle function, including analysis of the impact of iron status on function at the whole body, tissue, and molecular levels.

Iron Mobilization using Chelation and Phlebotomy

Trond Peder Flaten, PhD and Jan Aaseth, PhD

Dr. Flaten, Professor, Chemistry, Norwegian University of Science and Technology,Trondheim, Norway, and Dr. Aaseth, Professor, Medicine, Innlandet Hospital Trust, Norway, have worked with trace metals and metal mobilization in humans for several decades. They will address their most recent findings regarding iron chelation.

Background: Recently, a better understanding of how iron absorption plays a key feedback role in influencing both its metabolism and requirements has increased. The mechanism by which iron, especially non-heme iron, transits the intestinal epithelia is known to involve a variety of proteins, which serve to sequester or facilitate its passage into systemic circulation and tissues. Thus, iron stores respond in kind. An individuals absorptive and storage profile influence signaling and the activity of metabolic pathways involved in iron utilization, which, in turn, affect requirements.

Symposium G: Osteoporosis - From Risk Factors to Prevention and Treatment NTES / ISTERH -11 acknowledge the generous support from NycoMed Pharma AS and Novartis, Norway.

Chairs: Erik Fink Eriksen and Georges Boivin

Treatment of Bone Disease with Bisphosphonates

Erik Fink Eriksen, MD, PhD

Dr. Eriksen, Professor, Endocrinoloy, Oslo University Hospital, Norway, has conducted numerous clinical studies on the treatment of osteoporosis, a disease which affects one of every four women over the age of 60 years. In his studies he has found responsiveness to a once a year administration of a diphosphonate.

Strontium Ranelate a Promising Therapeutic Principle in Osteoporosis?

Georges Boivin, PhD

Dr. Boivin, Institut national de la sant et de las recherch medicale, University of Lyon, France, has several clinical studies on strontium ranelate. These suggest a possible new paradigm in the treatment of the devastating disease of osteoporosis.

Osteoporosis - Trace and Mineral Elements - a Brief Overview

Jan Aaseth, MD, PhD, Ole Andersen, Dr Med, and Georges Boivin, PhD

Dr. Aaseth, Research Coordinator, Medicine, Innlandet Hospital Trust, Norway, has worked with endocrinology and toxicology for several decades. With Dr. Andersen, Roskilde University, Denmakr and Dr. Boivin, Lyon, France, he gives a brief overview of the importance of trace substances in osteoporosis.

The Effects of Low-Level Cadmium Exposure on Bone Density

Margaret Trzcinka-Ochocka, PhD

Dr. Trzcinka-Ochocka and her group at Nofer Institute of Occupational Health, Lodz, Poland, have been involved in studies of effects of low-level cadmium exposure for several years. Their recent study is in contrast to the work carried out by others, in which environmental cadmium exposure affected bone density.

Background: Osteoporosis is a debilitating disease that is characterized by reduced mineral mass and changed micro-architecture of the bone. More than 200 million people are affected worldwide, with 2 million hip fractures estimated to occur annually. Countries with a Westernized lifestyle and regions in rapid transition have a higher incidence than developing countries. Because of the serious manifestations and the enormous costs of the disease, numerous investigators have evaluated the role of medications and supplementations with minerals and trace substances to reverse the progression of this disease. Although bisphosphonates are still the drugs of choice, strontium salts show great promise for the future.

Symposium H: Impact of Arsenic Exposure on Human Health: Approaches to Countering Toxicity.

Chairs: Parvez Haris and Habigul Ahsan

Selenium Counters Adverse Health Effects of Arsenic in Humans

Habibul Ahsan, MD

Dr. Ahsan, Professor, Health Studies, Medicine and Human Genetics, University of Chicago and Professor, Epidemiology, Columbia University, USA, is engaged in molecular epidemiology studies evaluating the role of selenium in countering arsenic toxicity at the molecular level, as well as in double-blind, randomized clinical trials in humans. He will discuss how selenium supplementation may prove to be an effective means to reduce risks of serious health consequences in millions of people chronically exposed to arsenic.

Arsenic Exposure, Dietary Patterns, and Skin Lesion Risk in Bangladesh

Brandon Pierce, PhD

Dr. Pierce, Assistant Professor, Department of Health Studies, The University of Chicago, USA, has investigated relationships between dietary patterns, arsenic exposure, and skin lesion risk. Using baseline food frequency questionnaire data from the Health Effects of Arsenic Longitudinal Study in Bangladesh, he will document how arsenical skin lesion risk in Bangladesh may be reduced by increasing dietary diversity and consumption of a diet rich in gourds and root vegetables.

Arsenic Exposure, Arsenic Methylation Capacity, and Cardiovascular Disease

Yu Chen, PhD, MPH

Dr. Chen, Associate Professor, Epidemiology, New York University School of Medicine, USA, will focus on how environmental and dietary factors are related to the risk of chronic diseases, including cancer and cardiovascular disease. He leads several epidemiologic studies on the influence of risk factors related to systemic inflammation on chronic diseases. He will present a lecture on the relationships between arsenic exposure, arsenic methylation capacity and development of cardiovascular disease.

Reducing Human Exposure to Arsenic through the Food Chain

Parvez Haris, PhD

Dr. Haris, Head, Biomedical and Environmental Health Group, De Montfort University, Leicester, United Kingdom, will explore relationships between diet, trace element, ethnicity and human health. He will describe the impact of a rice-based diet on human exposure to arsenic, as well as exposure to arsenic and toxic elements from the ancient practice of geophagy.

AsMetabolism in Residents from the Areas with As-Contaminated Groundwater in Vietnam: Effects of As Exposure Levels and Genetic Polymorphisms

Agusa Tetsuro, PhD

Dr. Tetsuro, Ehime University Center for Marine Environmental Studies, Division of Environmental Chemistry, Japan, has focused on human risk assessment of arsenic-contaminated regions in Asian developing countries using analyses of arsenic-related genes. He will present a lecture on the topic of arsenic exposure and genetic polymorsphisms in relation to arsenic metabolism in a population in Vietnam.

Background: Inorganic arsenic (iAs) is a non-threshold class I carcinogenic agent, which with other arsenic species, can be found in water and food from geogenic and anthropogenic processes. Exposure to iAs through drinking contaminated water and eating certain foods, and its impact on human health, are of increasing concern. Millions of people worldwide are exposed to high levels of arsenic through contaminated water. An association between exposure to inorganic arsenic and development of various diseases including different types of cancer and cardiovascular disease has been reported.Arsenic intake has been found to increase mortality for chronic diseases in Bangladesh. Progress is being made in understanding of arsenic metabolism and mechanisms underlying its toxic effects.Methods have been identified for countering the toxic effects of arsenic through various approaches such as selenium supplementation. Latest advances in the field and future directions will be presented.

Symposium I: Iodine Supplementation in Pregnancy: How Good is the Evidence?

Chair: Sheila Skeaff

Thyroid Disease in Pregnancy: An Appropriate Model to Ascertain the

Effects of Iodine Deficiency in Pregnancy?

Angela Leung, MD

Dr. Leung, Assistant Professor, Medicine, Boston University School of Medicine, USA, will describe thyroid dysfunction and iodine status of American pregnant women, including diagnosis and treatment.

Iodine in Pregnancy: Effects of Deficiency and Excess

Elizabeth Pearce, MD

Dr. Pearce, Associate Professor, Medicine, Boston University School of Medicine, USA, will review research, diagnosis and treatment concerning iodine status of American pregnant women.

Assessing Iodine Intakes in Pregnancy and Strategies for Improvement

Sheila Skeaff, PhD

Dr. Skeaff, Senior Lecturer, Human Nutrition, University of Otago, New Zealand, has investigated the iodine status of children and pregnant women in New Zealand, Australia, and India. She will summarize various dietary assessment methods that determine iodine intakes.

Iodine Supplementation Trials in Pregnancy

Alida Melse-Boonstra, PhD

Dr. Melse-Boonstra, Centre for Food Sciences and Division of Human Nutrition, Wageningen University, The Netherlands, will discuss her randomized, placebo-controlled intervention trial to determine the effect of iodine supplementation in pregnancy on biochemical and clinical outcomes in mothers and children.

Background. Iodine is integral to the thyroid hormones needed for normal growth and development, particularly of the brain. Pregnant women are susceptible to iodine deficiency because requirements increase by 50% in pregnancy. Although adverse consequences of severe to moderate deficiency in pregnancy are unequivocal (i.e., cretinism), the consequences of a mild deficiency are unclear. Recommended amounts/day in pregnancy are 250 ug (World Health Organization) and 150 ug (American Thyroid Association, New Zealand). Yet little evidence underpins this advice. Two studies have investigated the effect of supplementation of moderately iodine-deficient, pregnant women on functional outcomes in children, yet neither were randomized or controlled. The need for such trials in moderately iodine-deficient populations will be discussed.

Symposium J: Metal Carcinogenesis

Chair: Max Costa

Chromium-Induced Chromatin Remodeling

Alvaro Puga, PhD

Dr. Puga, Professor, Environmental Medicine, University of Cincinnati Medical School, USA, will discuss how Cr(VI) crosslinks histone deacetylase to the AHR promoter and prevent it from inducing P450 related genes.

Genomic Instability in Chromium Carcinogenesis

Anatoli Zhitkovich, PhD

Dr Zhitkovich, Professor, Pathology, Brown University, USA, has explored how chromium (Cr) (VI) causes a loss of mismatch repair through selections which leads to genomic instability. These processes are important in Cr (VI)- induced carcinogenesis.

Arsenic and the Nrf2-Keap1 Pathway

Donna Zhang, PhD

Dr. Zhang, Assistant Professor, Pharmacology and Toxicology, College of Pharmacy, University of Arizona, USA, has examined how arsenic activates NrF2 by degrading its inhibitor KEAP. Her research appears to disclose a novel mechanism of Nrf2 activation by arsenic through autophagy.

Effects of Carcinogenic Metals on Histone Tail Modifications

and Gene Expression in Humans

Max Costa, PhD

Dr. Costa, Professor and Chair, Environmental Medicine, New York University School of Medicine, USA, has determined how Ni induces alterations in post translational histone tail modifications by inhibiting oxidative histone demethylases. Refinery workers with high nickel exposures exhibited changes in histone tail lysine methylations and acetylations in their peripheral blood mononuclear cells. He also has investigated how Cr(VI) induces malignant transformation of human bronchial epithelial cells.

Background: A large number of studies have explored the molecular mechanisms of the carcinogenic potential of metals such as Cr(VI), nickel and arsenic. The present symposium aims at presenting new insights into these mechanisms

Symposium K: EURRECA: Variations in European Micronutrient Recommendations

Chair: Susan Fairweather-Tait

Iron Bioavailability and Dietary Reference Intakes

Susan Fairweather-Tait, PhD, DSc

Dr. Fairweather-Tait, Professor, Nutrition, University of East Anglia, United Kingdom, has been involved in studying the bioavailability of micronutrients in the context of setting micronutrient requirements. Her presentation will cover approaches for deriving trace element requirements, followed by an overview on bioavailability and how different expert bodies deal with the issue of bioavailability.

Zinc Requirements, Status and Health Outcomes in Humans

Nicola Mary Lowe, PhD

Dr. Lowe, Nutritional Biochemist and Senior Lecturer, University of Central Lancashire, United Kingdom, has a research interest in zinc. Her presentation will provide an overview of the inter-relationships between dietary zinc intakes, status and health outcomes in various population groups. The ways in which these relationships can be used to inform dietary zinc recommendations will be discussed.

A Systems Biology Approach to Trace Element Recommendations

Ben van Ommen, PhD

Dr. van Ommen, Program Director, Systems Biology, Netherlands Organization for Applied Scientific Research, Utrechsweg, Netherlands, has research interests that include nutritional systems biology and personalized nutrition. The biological knowledge of the mechanisms of action of specific trace elements now allows the determination of requirements based on functionality, instead of status. Since physiological functions in many cases are determined by multiple trace elements, the combination of -omics analysis and network biology can be used to derive personalized requirements of multiple trace elements.

Background: In Europe, micronutrient recommendations have been established by (inter)national committees of experts and are used by public health policy decision-makers to monitor and assess the adequacy of the diets of population groups. The approach that is utilized to create reference values for micronutrients, as well as the reference values themselves, varies considerably across countries. Harmonization is needed to improve nutrition policy and public health strategies. The EURRECA Network of Excellence (EURopean micronutrient RECommendations Aligned www.eurreca.org) is developing generic tools for systematically establishing and updating micronutrient reference values or recommendations.

Symposium L: Molecular Aspects of Copper and Zinc

Chair: James F. Collins

Molecular Analysis of Wilsons Patients: Direct Sequencing and MLPA Analysisin the ATP7B Gene and ATOX1 and COMMD1 Gene Analysis

Muriel Bost, PhD

Dr. Bost is from the Laboratory of Hereditary Diseases of Metabolism, France

A New Separation Procedure for Cu Prior to Stable Isotope Measurement by MC-ICPMS

F. Larner, PhD

Dr. Larner is from Imperial College, United Kingdom

Zinc Deficiency Reduces Kidney Erythropoietin Expression in Rats

Aki Konomi, PhD

Dr. Konomi is from Aichi Gakusen University, Japan

Novel Aspects of Copper in Iron Biology

James F Collins, PhD

Dr. Collins, Assistant Professor, Nutritional Biochemistry, University of Florida, Gainesville, Florida, USA, will discuss novel discoveries regarding the role of copper in overall body iron homeostasis. During iron deficiency, there is an enhanced expression of intestinal Atp7a (a copper exporter), an increase in liver and serum copper, and a concomitant increase in serum ferroxidase activity. These responses may be compensatory mechanisms to elevate iron-dependent functions in the body.

Background: This symposium focuses on aspects of copper that are relevant to human disease states. These include those associated with iron deficiency, perturbations in cardiovascular function and dysfunction of cellular energy production. The identification of sensitive biomarkers that can be used to detect copper deficiency in humans will be discussed, with the long term goal of being able to detect subclinical deficiencies with relevance to human health. Overall, this diverse group of investigators will present updates linking aspects of copper homeostasis to the development of pathological phenotypes in humans.

Symposium M: Functional and Neurotoxic Aspects of Zinc in the Brain

Chair: Atushi Takeda

Zinc Signaling in the Hippocampus and its Relation to Pathogenesis of Depression

Atsushi Takeda, PhD

Dr. Takeda, Associate Professor, Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan, has studied the role of zinc in brain functions and has indicated that zinc modulates synaptic plasticity such as long-term potentiation in the hippocampus and participates in learning and memory. He also has indicated neuropsychological symptoms such as depression under dietary zinc deficiency.

EAAC1 Gene Deletion Increases Intracellular Zinc Accumulation, Oxidative Stress and Neuronal Death after Transient Cerebral Ischemia

Sang Won Suh, PhD, MD

Dr. Suh, Professor, Physiology, Hallym University, College of Medicine, Korea, has studied zinc neurotoxicity in the brain. He is interested in the mechanisms of zinc neurotoxicity after transient cerebral ischemia. EAAC1 is a neuronal glutamate and cysteine transporter. EAAC1 uptake of cysteine provides substrate for neuronal glutathione synthesis, which plays a key role in both antioxidant defenses and intracellular zinc binding. He will describe how cysteine uptake by EAAC1 is important for zinc homeostasis and neuronal antioxidant function under ischemic conditions.

Free Zinc Ions Outside a Narrow Concentration Range are Toxic to a Variety of Cells

Christopher J. Frederickson, MD

Dr. Frederickson, Professor, Institute of Zinc in Biology, University of Texas Medical School, Galveston, USA, has studied that zinc is co-released with glutamate from glutamatergic neuron terminals and serves as a neuromodulator. In contrast, excessive zinc release is neurotoxic in neurological diseases. He will review recent advances in zinc neurotoxicity and its related mechanisms.

Molecular Mechanism of Zinc-Induced Neurotoxicity

Masahiro Kawahara, PhD

Dr. Kawahara, Professor, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Miyazaki, Japan, revealed that zinc caused drastic apoptotic death of GT1-7 cells (immortalized hypothalamic neurons). He investigated its molecular mechanism and searched for protective substances against zinc neurotoxicity among various foods. Among tested, he found that carnosine (-alanyl histidine), citrate, and histidine attenuated zinc-induced neurotoxicity. He will discuss the role of ER stress and calcium homeostasis in the neuronal death induced by zinc.

Background: The significance of zinc signaling is poorly understood in comparison with calcium signaling. Zinc signaling in the brain is important to maintain healthy brain and its importance is becoming recognizable.