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Journal Article 2008; 29(5): 609-613 PubMed PMID: 18987585 Citation  Keywords:  Animals, Antioxidants:pharmacology, Drug-Related Side Effects and Adverse Reactions, Herbicides:toxicity, Humans, Melatonin:pharmacology, Metals:toxicity, Neurotoxins:toxicity, Oxidative Stress:drug effects, Prescription Drugs:toxicity, Reactive Nitrogen .   

: The purpose of this brief review is to introduce the reader to the vast amount of published literature related to the free radical scavenging and antioxidative activity of melatonin. However, this review summarizes only a few of the many conditions in which melatonin has been found to be protective against oxidative/nitrosative damage. Melatonin ameliorates the extensive free radical-mediated damage that ensues following exposure to a wide variety of environmental insults. Concisely reviewed in this report are the protective effects of melatonin against toxic prescription drugs, neural toxins, herbicides and metals. The findings have clear implications for the utility of melatonin in toxicology....

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Journal Article 2006; 27(Suppl 1): 7-16 PubMed PMID: 17261999 Citation  Keywords:  Biomarkers:blood, Dental Amalgam:toxicity, Environmental Pollutants:toxicity, Humans, Hypersensitivity:diagnosis, Inflammation, Lymphocyte Activation, Metals:toxicity, T-Lymphocytes:immunology, Titanium:toxicity,.   

: Environmental factors are recognized as a cause of the increasing frequency of allergic and autoimmune diseases. In addition to external pollutants, metal ions released from dental restorations or from other body implants might trigger inflammation in susceptible subjects. In humans, genes governing metal-induced inflammation and autoimmunity are not yet known. In clinical praxis, metal-sensitive patients will present various symptoms ranging from oral mucosal changes and skin disease to excessive fatigue and autoimmune diseases. Since genetic markers of genetic susceptibility in man are not known, one has to rely on the phenototypic markers. Such biomarkers might be certain detoxification enzymes but also the presence of metal-specific memory cells in the blood. With the increasing use of metal implants in medicine and dentistry, it is important to have a proper tool for the diagnosis of metal allergy in susceptible subjects. After nickel, gold is now the second most common sensitizer. In addition to patch test, an in vitro blood test, an optimized commercially available lymphocyte transformation test (MELISA) is discussed. Both tests were used for the diagnosis of metal allergy in a selected group of 15 patients who suffered from clinical metal sensitivity in addition to other health problems. The concordance of the two tests was good but MELISA detected more metal allergies than patch test. The removal of incompatible dental material (RID) resulted in long-term health improvement in the majority of patients. We postulate that in vivo, metal ions activate T-cells, initiating systemic inflammation, which, through cytokines, affects the brain and hypothalamus-pituitary-adrenal axis. We postulate that in vivo metal ions will activate T-cells starting systemic inflammation which, through cytokines affect the brain and hypothalamus-pituitary-adrenal (HPA) axis. The treatment and rehabilitation of metal sensitive patients is based on a firm understanding and recognition of individual susceptibility. RID has to be done done with extreme caution and according to standard working protocol. If performed properly, this treatment can result in decreased systemic inflammation and improved health in sensitized patients....

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Case Reports 2006; 27(Suppl 1): 17-24 PubMed PMID: 17261998 Citation  Keywords:  Adult, Aged, Dental Amalgam:toxicity, Environmental Exposure, Female, Humans, Hypersensitivity:diagnosis, Immunoassay:methods, Lymphocyte Activation, Metals:toxicity, Middle Aged, Occupational Exposure, Reproducibility of Results, Sensitivity and Specific.   

OBJECTIVES: Chronic low-level metal exposure may result in metal sensitization and undesirable side-effects. The main sources of metal exposure are from the environment or from corrosion of dental metal alloys. Affected patients are routinely diagnosed with the epicutaneous (patch) test. However, such testing may induce false-positive (irritative) reactions and may in itself sensitize or exacerbate symptoms. Alternatively, MELISA (Memory Lymphocyte ImmunoStimulation Assay), an optimized lymphocyte transformation test (LTT), can be used. In this study we analyzed the overall frequency and distribution of metal sensitization among symptomatic, metal-exposed patients. In addition, we determined the reproducibility of the assay and assessed its clinical relevance for detecting and monitoring hypersensitivity to metals.

METHODS: To analyze the frequency and distribution of metal sensitization, blood from 700 consecutive patients was tested against a total of 26 metals in the validated LTT-MELISA. For reproducibility testing, 391 single metal tests from 63 patients were performed in parallel. Finally, to assess clinical relevance, 14 patients with known metal exposure showing local (dry mouth, Oral Lichen Planus, Burning Mouth Syndrome, eczema) and/or systemic (chronic infections, fatigue, autoimmune disorders, central nervous system disturbances, depression) effects were tested in LTT-MELISA. In 7 cases testing was repeated following removal of the allergy-causing metals or, in 2 additional cases, without therapeutic intervention.

RESULTS: Of the 700 patients tested, 74.6% responded to >/= 1 metal in LTT-MELISA, with a subgroup of 17.9% responding to >/= 3 metals. Reactivity was most frequent to nickel (68.2%), followed by cadmium (23.7%), gold (17.8%), palladium (12.7%), inorganic mercury (11.4%), molybdenum (10.8%), beryllium (9.7%), titanium dioxide (4.2%), lead (3.7%), and platinum (3.4%). Reproducibility was 94.9%, with most discordant results in a low-positive range. Removal of the alloys or prostheses containing allergenic metals resulted in remarkable clinical improvement correlating with a significant reduction or complete normalization of specific lymphocyte reactivity. In contrast, both LTT-MELISA reactivity and clinical symptoms remained unchanged in follow-up samples from the 2 patients who did not remove the source of metal exposure.

CONCLUSION: The optimized LTT-MELISA test is a clinically useful and reliable tool for identifying and monitoring metal sensitization in symptomatic metal-exposed individuals....

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