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BSAAM's Anti Ageing Conference London 2018
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AACL 2005 Speaker

Dr Vera Stejskal PhD
Associate Professor of Immunology, University of Stockholm and 1st Medical Faculty at Charles University, Prague, Czech Republic

Dr.Vera Stejskal received her doctoral degree from Charles University in Prague, Czech Republic. She has worked as a research scientist at the Institute of Experimental Biology and Genetics in Prague, Czech Republic; at the Dept. of Immunology, The University of Stockholm, Sweden; and as a Senior Research Adviser and Head of Immunotoxicology Group at AB ASTRA, Safety Assessment, Södertälje, Sweden. Dr. Stejskal is affiliated with the Dept of Clinical Chemistry, Danderyd's Hospital and Karolinska Institute, Stockholm, Sweden, conducting research in Clinical Immunotoxicology; and is affiliated to 1st Medical Faculty at Charles University, Prague, Czech Republic, where Dr. Stejskal teaches and directs research. Currently Dr. Stejskal is the owner of MELISA® trademark and of MELISA® patent in all major European countries Founder of MELISA® MEDICA foundation (1992). Dr. Stejskal has a great research interest in the field of Immunotoxicology at the Swedish Society of Toxicology (key person). She also is responsible for saving the bestselling drug, Prilosec®, for Astra by setting up a study that explained the mechanisms of drug side-effects in a one-month toxicology study. Upon the repeating the study with parasite-naive animals, no side-effects developed. MELISA®-like test was used for the demonstration of immunological memory to worm antigens in conventional but not in parasite-free animals. Dr. Stejskal is also a recipient of the EEC grant on Biotech program "In vitro Immunotoxicology", adviser to the World Health Organization, and is an expert witness to a US Congressional Committee that in 2002 investigated vaccine safety and thimerosal allergy. Dr. Stejskal is the author of more than 100 scientific publications in the field of allergy and immunotoxicology.

The role of metals in aging: Scientific evidence and case reports including
Alzheimer's, Parkinson's and Multiple Sclerosis
The role of metals in human aging is currently a hot research topic worldwide. Abnormal deposition of iron in the brain of patients suffering from neurodegenerative diseases such as Parkinson’s, Alzheimer’s and multiple sclerosis has been firmly established. It is less known that the exposure to mercury and other metals may result in disturbance of the brain iron transport and thus in abnormal iron deposition. The release of metallic mercury from dental amalgam, intake of methyl-mercury through ingestion of contaminated fish, exposure to cadmium, lead and nickel from foods and cigarette smoke are just few examples of daily metal exposure which may cause health problems in susceptible subjects.

The danger of heavy and transition metals resides in their physicochemical properties; binding to sulfur (SH) and other groups in the mitochondria, enzymes and cell proteins. Fat-containing organs such as brain or collagen-containing structures are especially rich in SH-groups and therefore vulnerable to metal binding. Metals induce free radical formation, inactivate enzyme and mitochondrial activity and act as triggers in inflammation, allergy and autoimmunity.
In this lecture I will explain the role of metal-induced inflammation in diseases of allergic and autoimmune origin with the onset in middle age and later in life.
The MELISA® test has been developed to accurately diagnose metal allergy. MELISA® (MEmory Lymphocyte Immuno Stimulation Assay) is scientifically validated and widely published (www.melisa.org). Chronic exposure to metals through jewelry, dental restorations, hip and knee prosthesis, foods or even coins can sensitize genetically predisposed individuals and induce a so-called delayed type hypersensitivity reaction. Another source of metal exposure is cigarette smoke which contains nickel, cadmium, manganese mercury, lead and arsenic. Hygiene and cosmetic products contain metal pigments including E171 (titanium dioxide), E172 (iron oxide), cadmium and lead pigments as well as mercury-based preservatives (thimerosal/merthiolate and phenylmercury). Thimerosal, an organic mercury-based preservative, has until recently been used in childhood vaccines. This is the reason why thimerosal is the most frequent allergen in children and adolescents, surpassing the most frequent adult allergen--nickel.
In contrast to immediate type allergy, mediated by IgE antibodies (Type I allergy), cellular hypersensitivity (Type IV allergy) is mediated by T-lymphocytes previously sensitized to a given allergen.
A certain type of white blood cell, called memory cell, remembers its previous encounter with a particular foreign substance (antigen). Following renewed contact with the allergen, memory cells grow and divide. The role of activated lymphocytes is to protect against foreign invaders such as bacteria and viruses but also to eliminate abnormal cells such as cancer cells.
Corroded metal ions bind to body proteins such as enzymes and membrane antigens and alter their tertiary structure. In genetically susceptible individuals, metal-modified cells are falsely recognized as “foreign” entity and consequently destroyed by the patient’s immune system. This might start an autoimmune process.

It is important to differentiate between metal allergy and metal toxicity. MELISA® does not measure the level of metals in a patient’s body; it measures whether the patient is allergic to metals or not. For example, hair analysis may show levels of mercury or other substances which are below the official “safe limit” – but the patient can still be allergic and react vigorously to the antigen. For allergic individuals, there is no “safe” limit. Even trace amounts of a substance pose danger if the substance triggers an allergic reaction.

The most frequent in vitro metal reactivity (allergy) found in all patients groups in MELISA® is nickel. In Sweden, inorganic mercury was the second most common sensitizer in 900 patients suffering from chronic fatigue syndrome, fibromyalgia and autoimmune diseases often reflecting known clinical metal allergy of the patient. Other metals often positive in MELISA® are gold, palladium, molybdenum, chromium and titanium.

Metal-induced inflammation may be involved in the pathology of various diseases such as skin diseases (psoriasis, eczema), neurological diseases (multiple sclerosis, Alzheimer’s, Parkinson’s disease, amyotrophic lateral sclerosis), rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease) and psychiatric diseases (depression, epilepsy). Metal-induced pathology is also indicated in cardiovascular diseases. In patients with idiopathic cardiomyopathy, the following concentrations of heavy metals were found by neutron activation analysis; mercury: 178,400 ng/g (normal range: 5-480), antimony: 19,260 ng/g (normal range: 2-35), chromium 2,300 ng/g (normal range: 11-480), gold 26 ng/g (normal range: 0.045), arsenic 625 ng/g (normal range: 4.4-14 ng/g) and barium 7,360 ng/g (normal range:7.6-2,020 ng/g). Another example of metal-triggered inflammation is coronary in-stent re-stenosis which might be triggered by contact allergy to nickel, chromate or molybdenum ions released from stainless steel stents. Metal-specific lymphocyte responses to mercury, cadmium, lead, antimony and arsenic were detected by MELISA® in patients with cardiovascular diseases. Replacement of dental metals by non-metallic materials by a knowledgeable dentist followed by chelation resulted in sustancial improvement of the symptoms in many patients.

In the case of berylliosis, a sarcoidosis-like disease, a beryllium-specific lymphocyte proliferation test based on the same principle as MELISA® is used as a golden standard by the US industry to screen workers for beryllium allergy. It has been found that asymptomatic workers with memory cells reacting to beryllium will – if beryllium exposure continues – develop a serious lung disease. This will not happen if the affected workers are relocated to a beryllium-free environment. Thus, in addition to long suffering, considering savings in sick leave costs are obtained.
Recently, children and adolescents suffering from autistic disorders have shown increased in vitro lymphocyte reactivity to several metals, especially mercury compounds such as thimerosal, aluminum (which is another component of vaccines) and other metals.

Long-term studies in metal-allergic patients indicate that anti-oxidant therapy combined with the reduction of metal body burden by replacement of allergenic dental metals followed by chelation therapy favorably affected patients’ health. The beneficial effects of this protocol can be demonstrated by the decreased metal-specific lymphocyte reactivity in vitro.

References:
Marked elevation of myocardic trace elements in idiopathic dilated cardiomyopathy compared with secondary cardiac dysfunction, Frustaci, A et. al, Journal of American College of Cardiology, 1999;33:1578-83
MELISA® - an in vitro tool for the study of metal allergy, Stejskal, Vera, PhD, et. al, Toxicology In Vitro, 1994;8:991-1000
Metal-specific lymphocytes: biomarkers of sensitivity in man, Stejskal, Vera, PhD, et. al, Neuroendocrinology Letters 1999; 20:289–298
Mercury-Specific Lymphocytes: An indication of Mercury Allergy in Man,
Stejskal, Vera, PhD, et. al, Journal of Clinical Immunology, 1996;16:31-40
Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis, Köster, R, et. al, The Lancet, 2000;356:1895-1897
The beneficial effect of amalgam replacement on health in patients with autoimmunity, Prochazkova, Jarmila, et. al, Neuroendocrinology Letters 2004;25(3):211-218
The role of metals in autoimmunity, Stejskal Jenny, MD., et. al, Neuroendocrinology Letters 1999; 20:351–364
Validity of MELISA® for metal sensitivity testing, Valentine-Thon, Elizabeth, PhD and Schiwara, Hans-Walter, Neuroendocrinology Letters 2003;24(1/2):57–64

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