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“During the past 50 years, a series of key UN conferences have established a framework to minimize human health risks from environmental exposures to key chemicals. In January 2013, more than 140 countries agreed to the text of new treaty to minimize Hg effects on the environment (the Minamata Convention). Dental caries is omnipresent around the globe, affecting 60% to 90% of school children and most adults, and producing discomfort that affects quality of life. Dental amalgam is frequently used to treat carious lesions and its use releases mercury into the environment. The best way to avoid the use of dental amalgam is to emphasize caries prevention. Alternatives to amalgam are suitable in some applications, but no replacement for amalgam has been found for large posterior restorations. For any restorative material, safety and environmental impacts are part of clinical risk assessment. Safety is freedom from unacceptable risks. Risk is a combination of probability of exposure and severity of harm. Best management practices are crucial to manage dental amalgam, but these impose additional that are disproportionately more for developing countries. The Minamata Convention seeks a phase-out of all mercury-based products except dental amalgam, where a phase-down is the present goal. For dentistry, the most important focus is the promotion of caries prevention and research on new materials.”

“This article outlines the subjects presented and discussed at the December 2012 IADR Dental Materials Innovation Workshop held at King’s College London. Incorporating new materials and techniques into clinical practice was considered from 4 perspectives: (1) Accelerating the “research to regulatory approval” process was presented with current developments in the United States, with the National Institutes of Health/Food and Drug Administration process as a working example; (2) intellectual property and regulatory requirements were discussed across the well-established US and EU frameworks, as well as the more recently developed procedures across Brazil, Russia, India, and China; (3) the challenges and opportunities of incorporating innovations into dental education were considered with reference to the future needs of both students and faculty; and (4) the key but difficult and unpredictable step of translating such innovations into routine dental practice was then explored. Constructive and far-ranging discussion among the broadly based Workshop participants (from dental research, education, practice, and industry, as well as environmental organizations and the World Health Organization) mapped out key issues for the future. The focus was on facilitating the more timely adoption of improvements in both materials and techniques to improve patient health and health systems, while minimizing environmental impact.”

“Background. Multiple chemical sensitivity (MCS) is a chronic condition characterized by an exaggerated response to toxicants. We ascertained the prevalence of allergy to metals and toxicological aspects in MCS patients. Methods. We conducted a retrospective review of medical records of 41 patients with MCS. We performed patch testing (n = 21) for dental series and did lymphocyte transformation test (n = 18) for metals. We measured mercury in samples of blood (n = 19), urine (n = 19), saliva (n = 20), and scalp hair (n = 17) to investigate the association between mercury levels and cases of MCS. Results. The prevalence of metal immune hypersensitivity in a subset of 26 patients was 92.3 percent. Elevations of mercury occurred in 81.2 percent (26 of 32). The mean (±SD) in blood concentrations of mercury was 7.6 ± 13.6 μ g/L; mean in urine was 1.9 ± 2.5 μ g/L; mean in scalp hair was 2.2 ± 2.5 μ g/g; mean in saliva was 38.1 ± 52.1 μ g/L. Subgroup analyses showed that elevation of mercury levels in biological matrices were associated with mercury amalgams in patients with MCS (22 patients), compared with controls (8 patients) (odds ratio 11 : 95 percent confidence interval 1.5 to 81.6; P = 0.023). Conclusions. Our data show an increased prevalence of metal allergy and elevation of mercury levels in bioindicators among patients with MCS.”

“The role of thimerosal containing vaccines in the development of autism spectrum disorder (ASD) has been an area of intense debate, as has the presence of mercury dental amalgams and fish ingestion by pregnant mothers. We studied the effects of thimerosal on cell proliferation and mitochondrial function from B-lymphocytes taken from individuals with autism, their nonautistic twins, and their nontwin siblings. Eleven families were examined and compared to matched controls. B-cells were grown with increasing levels of thimerosal, and various assays (LDH, XTT, DCFH, etc.) were performed to examine the effects on cellular proliferation and mitochondrial function. A subpopulation of eight individuals (4 ASD, 2 twins, and 2 siblings) from four of the families showed thimerosal hypersensitivity, whereas none of the control individuals displayed this response. The thimerosal concentration required to inhibit cell proliferation in these individuals was only 40% of controls. Cells hypersensitive to thimerosal also had higher levels of oxidative stress markers, protein carbonyls, and oxidant generation. This suggests certain individuals with a mild mitochondrial defect may be highly susceptible to mitochondrial specific toxins like the vaccine preservative thimerosal.”

“Previously, we reviewed biological evidence that mercury could induce autoimmunity and coronary arterial wall relaxation as observed in Kawasaki syndrome (KS) through its effects on calcium signaling, and that inositol 1,4,5-triphosphate 3-kinase C (ITPKC) susceptibility in KS would predispose patients to mercury by increasing Ca2+ release. Hg2+ sensitizes inositol 1,4,5-triphosphate (IP3) receptors at low doses, which release Ca2+ from intracellular stores in the sarcoplasmic reticulum, resulting in delayed, repetitive calcium influx. ITPKC prevents IP3 from triggering IP3 receptors to release calcium by converting IP3 to inositol 1,3,4,5-tetrakisphosphate. Defective IP3 phosphorylation resulting from reduced genetic expressions of ITPKC in KS would promote IP3, which increases Ca2+ release. Hg2+ increases catecholamine levels through the inhibition of S-adenosylmethionine and subsequently catechol-O-methyltransferase (COMT), while a single nucleotide polymorphism of the COMT gene (rs769224) was recently found to be significantly associated with the development of coronary artery lesions in KS. Accumulation of norepinephrine or epinephrine would potentiate Hg2+-induced calcium influx by increasing IP3 production and increasing the permeability of cardiac sarcolemma to Ca2+. Norepinephrine and epinephrine also promote the secretion of atrial natriuretic peptide, a potent vasodilator that suppresses the release of vasoconstrictors. Elevated catecholamine levels can induce hypertension and tachycardia, while increased arterial pressure and a rapid heart rate would promote arterial vasodilation and subsequent fatal thromboses, particularly in tandem. Genetic risk factors may explain why only a susceptible subset of children develops KS although mercury exposure from methylmercury in fish or thimerosal in pediatric vaccines is nearly ubiquitous. During the infantile acrodynia epidemic, only 1 in 500 children developed acrodynia whereas mercury exposure was very common due to the use of teething powders. This hypothesis mirrors the leading theory for KS in which a widespread infection only induces KS in susceptible children. Acrodynia can mimic the clinical picture of KS, leading to its inclusion in the differential diagnosis for KS. Catecholamine levels are often elevated in acrodynia and may also play a role in KS. We conclude that KS may be the acute febrile form of acrodynia.”

“The benefit of the nutritious elements in fish is insufficient for explaining the controversial finding regarding prenatal mercury (Hg) exposure and neurodevelopment; the varying frequency of susceptible genes among these populations may shed light on these observations. However, limited studies have been reported on the association between genetic susceptibility of prenatal Hg exposure and child development. Apolipoprotein E (APOE, protein; Apoe, gene) is a major protein transporter expressed in the brain. The Apoe epsilon 4 (ε4) allele is associated with poor neural repair function and is a risk factor associated with Alzheimer disease. We conducted a prospective cohort study in 2004 and 2005. In this study, 168 subjects were recruited at delivery and followed up at two years of age, and genetic polymorphisms of Apoe were included to assess genetic susceptibility and to determine the relationship between Hg concentrations in cord blood and neurodevelopment. The results showed that adverse effects on neurodevelopment were consistently associated with prenatal Hg exposure in all subtests of Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) among ε4 carriers as assessed by both simple linear and multiple linear regression models. After controlling for confounding factors, statistical significance was found in the subtests of cognition tests (β=-8.47, 95% confidence interval (CI)=-16.10 to -0.84), social tests (β=-11.02, 95% CI=-20.85 to -1.19) and the whole test of CDIIT (β=-10.45, 95% CI=-17.36 to -3.54) in a multiple linear regression model. Additionally, the interaction effect between gene polymorphisms of Apoe and Hg levels was significant in the whole test CDIIT and subtests of cognition, language and fine motor tests. In conclusion, Apoe modifies the adverse effects of cord blood Hg on neurodevelopment at the age of two years.”

“Kidney injury from mercury is known to cause dose-related tubular dysfunction and idiosyncratic nephrotic syndrome according to various case reports. Motivated by a patient with subacute-onset nephrotic syndrome, histologic features of secondary focal segmental glomerulosclerosis, and concurrent mercury toxicity, we conducted a systematic review to explore renal histologic changes in patients with toxic mercury exposures and nephrotic syndrome. Data were extracted from a patient’s clinical record. MEDLINE/Ovid was searched from 1950 to November 2010 using a prespecified search strategy. Two nephrology textbooks and the UpToDate online database also were searched. Inclusion criteria were studies of humans with nephrotic syndrome, nephrotic-range proteinuria, or kidney biopsy results reported. There were no exclusion criteria. We identified 27 other reports of 42 patients with nephrotic syndrome or nephrotic-range proteinuria. Of the 26 individuals, including our patient, who underwent kidney biopsy, histology showed glomerular disease in 21. Of these 20 biopsies, 4 showed minimal change disease and 15 showed membranous glomerulonephritis. Mercury exposure can lead to various glomerular lesions; we emphasize the importance of a careful occupational and dietary history in elucidating a cause for the undetermined nephrotic syndrome.”