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“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.”

“Mercury (Hg) has been used for millennia in many applications, primarily in artisanal mining and as an electrode in the chlor-alkali industry. It is anthropogenically emitted as a pollutant from coal fired power plants and naturally emitted, primarily from volcanoes. Its unique chemical characteristics enable global atmospheric transport and it is deposited after various processes, ultimately ending up in one of its final sinks, such as incorporated into deep sediment or bioaccumulated, primarily in the marine environment. All forms of Hg have been established as toxic, and there have been no noted biological benefits from the metal. Throughout time, there have been notable incidents of Hg intoxication documented, and the negative health effects have been documented to those chronically or acutely exposed. Today, exposure to Hg is largely diet or occupationally dependent, however, many are exposed to Hg from their amalgam fillings. This paper puts a tentative monetary value on Hg polluted food sources in the Arctic, where local, significant pollution sources are limited, and relates this to costs for strategies avoiding Hg pollution and to remediation costs of contaminated sites in Sweden and Japan. The case studies are compiled to help policy makers and the public to evaluate whether the benefits to the global environment from banning Hg and limiting its initial emission outweigh the benefits from its continued use or lack of control of Hg emissions. The cases we studied are relevant for point pollution sources globally and their remediation costs ranged between 2,500 and 1.1 million US dollars kg(-1) Hg isolated from the biosphere. Therefore, regulations discontinuing mercury uses combined with extensive flue gas cleaning for all power plants and waste incinerators is cost effective.”

“Thimerosal is an organomercury compound with sulfhydryl-reactive properties. The ability of thimerosal to act as a sulfhydryl group is related to the presence of mercury. Due to its antibacterial effect, thimerosal is widely used as preservatives and has been reported to cause chemically mediated side effects. In the present study, we showed that the molecular mechanism of thimerosal induced apoptosis in U937 cells. Thimerosal was shown to be responsible for the inhibition of U937 cells growth by inducing apoptosis. Treatment with 2.5-5 microM thimerosal but not thiosalicylic acid (structural analog of thimerosal devoid of mercury) for 12 h produced apoptosis, G(2)/M phase arrest, and DNA fragmentation in a dose-dependent manner. Treatment with caspase inhibitor significantly reduced thimerosal-induced caspase 3 activation. In addition, thimerosal-induced apoptosis was attenuated by antioxidant Mn (III) meso-tetrakis (4-benzoic acid) porphyrin (Mn-TBAP). These data indicate that the cytotoxic effect of thimerosal on U937 cells is attributable to the induced apoptosis and that thimerosal-induced apoptosis is mediated by reactive oxygen species generation and caspase-3 activation.”

“People in developing countries are often considered at greater risk of mercury (Hg) poisoning due to a variety of factors including a lack of awareness regarding their occupational risks. Individuals requiring urine mercury (U-Hg) analysis at the Center for Toxicological Investigations of the University of Carabobo (CITUC), between 1998 and 2002 were studied to identify demographic characteristics associated to U-Hg levels. The studied population included individuals with a history of exposure (or related exposures) to Hg processes, and was comprised of 1159 individuals (65 children, 1094 adults) ages 0.58-79 years old, mean 36.63+/-12.4. Children’s geometric mean U-Hg levels were 2.73 microg/g Creatinine (Ct) and in adults 2.55 microg/g Ct. The highest frequency of adults’ occupations were shipyard workers (35.47%), dentists (23.5%), lab technicians (11.43%), dental employees 10.42% and miners (10.2%). Chemical laboratory technicians had the highest mean U-Hg (4.46 microg/g Ct). Mean U-Hg levels in female adults (3.45 microg/g Ct) were statistically superior to levels in male adults (2.15 microg/g Ct). Two of the 172 women in reproductive age, had U-Hg levels higher than 78 microg/g Ct. Individuals from Falcon State were found to have the highest mean U-Hg (4.53 microg/g Ct). U-Hg levels higher than permissible limits were found in only 2 states (Carabobo and Bolivar) with a total of 24 cases. Although the results of this investigation were highly variable, the findings can be used to examine circumstances which influence mercury toxicity trends, and possibly used in future studies working to identify Hg exposures.”

“Arachidonic acid (AA) participates in a reacylation/deacylation cycle of membrane phospholipids, the so-called Lands cycle, that serves to keep the concentration of this free fatty acid in cells at a very low level. To manipulate the intracellular AA level in U937 phagocytes, we have used several pharmacological strategies to interfere with the Lands cycle. We used inhibitors of the AA reacylation pathway, namely thimerosal and triacsin C, which block the conversion of AA into arachidonoyl-CoA, and a CoA-independent transacylase inhibitor that blocks the movement of AA within phospholipids. In addition, we used cells overexpressing group VIA phospholipase A(2), an enzyme with key roles in controlling basal fatty acid deacylation reactions in phagocytic cells. All of these different strategies resulted in the expected increase of cellular free AA but also in the induction of cell death by apoptosis. Moreover, when used in combination with any of the aforementioned drugs, AA itself was able to induce apoptosis at doses as low as 10 muM. Blocking cyclooxygenase or lipoxygenases had no effect on the induction of apoptosis by AA. Collectively, these results indicate that free AA levels within the cells may provide an important cellular signal for the onset of apoptosis and that perturbations of the mechanisms controlling AA reacylation, and hence free AA availability, may decisively affect cell survival.”

“OBJECTIVES:

This study was done to evaluate the results and clinical relevance of an optimized lymphocyte proliferation test, MELISA, for metal-induced inflammation in patients with CFS-like symptoms. The treatment of patients consisted of the replacement of incompatible dental materials (RID) together with supportive anti-oxidant therapy.

DESIGN OF THE STUDY:

513 patients were tested by MELISA at the beginning of the study. Out of this group, 248 patients were available for follow-up MELISA after RID.

METHODS:

In MELISA, lymphocytes are isolated from the blood and cultivated with different metal salts in tissue culture medium containing 10% inactivated human AB+ serum or autologous serum. After 5 days, the presence of metal-reactive lymphocytes are measured by isotope labelling of newly formed DNA in growing lymphoblasts and evaluated by calculating the Stimulation Index.

RESULTS:

Nickel was the most common sensitizer, followed by inorganic mercury, thimerosal, lead, cadmium, palladium and gold. After RID treatment, a decrease of metal-specific lymphocyte responses in patients who reacted to metals at the beginning of the study could be observed. The cultivation of lymphocytes in autologous and homologous serum did not significantly affect the results. Simultaneous, the health status of patients improved as well.

CONCLUSIONS:

Replacement of incompatible dental materials resulted in down-regulation of metal-induced lymphocyte sensitivity in vitro, as well as in the improvement of health status of majority of patients with unspecific CFS-like symptoms.”

“Thiomersal is used as a preservative in vaccines given to small children. The metabolic product of thiomersal is ethylmercury and its distribution and kinetics are still not known, especially at this early age. The purpose of this study was to compare the body distribution of two forms of mercury: organic (thiomersal) and inorganic (mercury(2+) chloride) in very young, suckling rats. Mercury was applied subcutaneously three times during the suckling period on days 7, 9 and 11 of pups age, imitating the vaccination of infants. A single dose of mercury was equimolar in both exposed groups, i.e. 0.81 micromol Hg kg(-1). At 14 days of age the animals were killed and the total mercury analysed in blood and organs (kidney, liver and brain). The analytical method applied was total decomposition, amalgamation, atomic absorption spectrometry. The results showed that the level of mercury was higher in the liver and kidney of the inorganic mercury group than in the thiomersal exposed group. However, the brain and blood concentrations of mercury were higher in the thiomersal exposed group. These results need to be clarified by additional data on the kinetic pathways of ethylmercury compared with inorganic mercury.”

“To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001). Porphyrin levels were unchanged in Asperger’s disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger’s. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.”