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“BACKGROUND:
Thimerosal, a mercury-containing preservative, is one of the most widely used preservatives and found in a variety of biological products. Concerns over its possible toxicity have reemerged recently due to its use in vaccines. Thimerosal has also been reported to be markedly cytotoxic to neural tissue. However, little is known regarding thimerosal-induced toxicity in muscle tissue. Therefore, we investigated the cytotoxic effect of thimerosal and its possible mechanisms on mouse C2C12 myoblast cells.

METHODOLOGY/PRINCIPAL FINDINGS:
The study showed that C2C12 myoblast cells underwent inhibition of proliferation and apoptosis after exposure to thimerosal (125-500 nM) for 24, 48 and 72 h. Thimerosal caused S phase arrest and induced apoptosis as assessed by flow cytometric analysis, Hoechst staining and immunoblotting. The data revealed that thimerosal could trigger the leakage of cytochrome c from mitochondria, followed by cleavage of caspase-9 and caspase-3, and that an inhibitor of caspase could suppress thimerosal-induced apoptosis. Thimerosal inhibited the phosphorylation of Akt(ser473) and survivin expression. Wortmannin, a PI3K inhibitor, inhibited Akt activity and decreased survivin expression, resulting in increased thimerosal-induced apoptosis in C2C12 cells, while the activation of PI3K/Akt pathway by mIGF-I (50 ng/ml) increased the expression of survivin and attenuated apoptosis. Furthermore, the inhibition of survivin expression by siRNA enhanced thimerosal-induced cell apoptosis, while overexpression of survivin prevented thimerosal-induced apoptosis. Taken together, the data show that the PI3K/Akt/survivin pathway plays an important role in the thimerosal-induced apoptosis in C2C12 cells.

CONCLUSIONS/SIGNIFICANCE:
Our results suggest that in C2C12 myoblast cells, thimerosal induces S phase arrest and finally causes apoptosis via inhibition of PI3K/Akt/survivin signaling followed by activation of the mitochondrial apoptotic pathway.”

“Mammalian brain development is regulated by the action of thyroid hormone (TH) on target genes. We have previously shown that the perinatal exposure to thimerosal (TM, metabolized to ethylmercury) exerts neurotoxic effects on the developing cerebellum and is associated with a decrease in cerebellar D2 activity, which could result in local brain T3 deficiency. We have also begun to examine TM effect on gene expression. The objective of this study was to expand on our initial observation of altered cerebellar gene expression following perinatal TM exposure and to examine additional genes that include both TH-dependent as well as other genes critical for cerebellar development in male and female neonates exposed perinatally (G10-G15 and P5 to P10) to TM. We report here for the first time that expression of suppressor-of-white-apricot-1 (SWAP-1), a gene negatively regulated by T3, was increased in TM-exposed males (61.1% increase), but not in females; (p<0.05). Positively regulated T3-target genes, Purkinje cell protein 2 (Pcp2; p=0.07) and Forkhead box protein P4 (FoxP4; p=0.08), showed a trend towards decreased expression in TM-exposed males. The expression of deiodinase 2 (DIO2) showed a trend towards an increase in TM-exposed females, while deiodinase 3 (DIO3), transthyretin (TTR), brain derived neurotrophic factor (BDNF) and reelin (RELN) was not significantly altered in either sex. Since regulation of gene splicing is vital to neuronal proliferation and differentiation, altered expression of SWAP-1 may exert wide ranging effects on multiple genes involved in the regulation of cerebellar development. We have previously identified activation of another TH-dependent gene, outer dense fiber of sperm tails 4, in the TM exposed male pups. Together, these results also show sex-dependent differences between the toxic impacts of TM in males and females. Interestingly, the genes that were activated by TM are negatively regulated by TH, supporting our hypothesis of local brain hypothyroidism being induced by TM and suggesting a novel mechanism of action TM in the developing brain.”

“OBJECTIVES:

Intraoral exposure to dental restorations can cause contact allergy that may induce carcinogenesis. We investigated the relationship of intraoral metal contact allergy to epithelial carcinogenesis.

METHODS:

The prevalence of positive patch test reactions to dental restoration metals in 65 prospectively enrolled patients with newly or previously diagnosed oral squamous cell carcinoma (SCC) was compared to that in 48 control patients. The relative risk of oral SCC was estimated by calculating odds ratios for exposure to dental metals resulting in allergy.

RESULTS:

Of the 65 patients with oral SCC, 34% were allergic to at least 1 adjacent metal. They were 1.57 times as likely as control patients to have metal contact allergy (odds ratio, 1.57; 95% confidence interval, 0.65 to 3.80) and more than 3 times as likely to react to mercury (odds ratio, 3.20; 95% confidence interval, 0.42 to 33.20).

CONCLUSIONS:

Patients with oral SCC who have metal dental restorations should undergo patch testing and possible removal of the restorations if their reactions are positive.”

“BACKGROUND:

Dental amalgam is approximately 50% metallic mercury and releases mercury vapor into the oral cavity, where it is inhaled and absorbed. Maternal amalgams expose the developing fetus to mercury vapor. Mercury vapor can be toxic, but uncertainty remains whether prenatal amalgam exposure is associated with neurodevelopmental consequences in offspring.

OBJECTIVE:

To determine if prenatal mercury vapor exposure from maternal dental amalgam is associated with adverse effects to cognition and development in children.

METHODS:

We prospectively determined dental amalgam status in a cohort of 300 pregnant women recruited in 2001 in the Republic of Seychelles to study the risks and benefits of fish consumption. The primary exposure measure was maternal amalgam surfaces present during gestation. Maternal occlusal points were a secondary measure. Outcomes were the child’s mental (MDI) and psychomotor (PDI) developmental indices of the Bayley Scales of Infant Development-II (BSID-II) administered at 9 and 30 months. Complete exposure, outcome, and covariate data were available on a subset of 242 mother-child pairs.

RESULTS:

The number of amalgam surfaces was not significantly (p>0.05) associated with either PDI or MDI scores. Similarly, secondary analysis with occlusal points showed no effect on the PDI or MDI scores for boys and girls combined. However, secondary analysis of the 9-month MDI was suggestive of an adverse association present only in girls.

CONCLUSION:

We found no evidence of an association between our primary exposure metric, amalgam surfaces, and neurodevelopmental endpoints. Secondary analyses using occlusal points supported these findings, but suggested the possibility of an adverse association with the MDI for girls at 9 months. Given the continued widespread use of dental amalgam, we believe additional prospective studies to clarify this issue are a priority.”

“Mercury is a ubiquitous environmental toxicant that causes a wide range of adverse health effects in humans. Three forms of mercury exist: elemental, inorganic and organic. Each of them has its own profile of toxicity. The aim of the present study was to determine the effect of thimerosal, a topical antiseptic and preservative in vaccines routinely given to children, methyl mercury, and mercuric chloride on cellular viability measured by MTT in Jurkat T cells, a human T leukemia cell line. The treatment of Jurkat T cells with thimerosal caused a significant decrease in cellular viability at 1 ?M (25%, p<0.05; IC50: 10 ?M). Methyl mercury exhibited a significant decrease in cellular viability at 50 ?M (33%, p<0.01; IC50: 65 ?M). Mercuric chloride (HgCl2) did not show any significant change in cellular survival. Our findings showed that contrary to thimerosal and methyl mercury, mercuric chloride did not modify Jurkat T cell viability.”

“While its use has essentially been eliminated in many countries, dental amalgam is now being considered for a global phase-out in the ongoing mercury treaty negotiations1 and in the European Union (BIO 2012) because of significant environmental concerns. The negative effects of mercury releases related to amalgam use are widely recognized in countries where its use has been prevalent: it is often the largest source of mercury in municipal wastewater as well as an increasing source of mercury air pollution from crematoria. On the other hand, high-quality mercury-free alternatives have long been available. While most dental professionals charge lower prices for amalgam fillings than for mercury-free alternatives, this paper shows that when factoring in “external” environmental and societal costs,2 amalgam is a higher-priced dental material by far (Hylander and Goodsite 2006). Ultimately, society pays for mercury releases related to amalgam use through additional pollution control costs, the loss of common (public-owned) resources, and the health effects associated with mercury releases and contamination (MPP 2008).”

“The health and environmental risks associated with mercury (Hg) are well known and have led the Commission to adopt an EU Mercury Strategy in 2005(1), with the aim to ‘reduce mercury levels in the environment and human exposure, especially from methylmercury in fish’. The review of the Strategy’s implementation(2), in 2010, acknowledged the progress made with regard to a number of actions proposed in 2005 such as the adoption of the Mercury Export Ban Regulation(3), the phase-out of mercury use in certain measuring devices under the REACH Regulation4, the submission of additional mercury use restriction proposals under REACH, and the EU’s contribution to the progress of international negotiations on the global mercury treaty. The review also highlighted areas for further improvement, among which the remaining uses of mercury in several applications where Hg-free alternatives exist and are already used to some extent; this concerns in particular dental amalgam and button cell batteries, which are the subject of the present study.”

“In dentistry, there is a lot of controversy about the topic of silver mercury fillings; are they safe or not safe? There are many articles written on the pros and cons of these types of fillings. It is difficult to quantify and to assess the effects in each individual. It is not easy to identify silver mercury fillings as the cause if illness presents or if the fillings contributed to illness, except in extreme toxicity cases. Refer to the beginning sections of this review paper concerning the science and mechanism of how mercury interconnects with body tissues and functions.
Environmental doctors investigate heavy metal toxicity as part of their overall wellness regiment to help their patients with health concerns. These doctors look at sources of metals when the patient’s lab reports/diagnostic tests show high levels of mercury and other metals. They investigate what sources are contributing and how to reduce the burden on the body. The doctor may prescribe the safe removal of silver mercury fillings so as not to create an additional burden on the body and to help their patient heal. Thus, when removing amalgams, additional steps help ensure that the patient is protected.”

“New filling materials were introduced in Norway in the 1970s, and were gradually preferred for aesthetic reasons. Focus on dental amalgam as an environmental problem emerged during the 1980s as part of a broader policy to limit emissions of mercury. In 1991 the health authorities issued guidelines recommending dentists to reduce the use of dental amalgam, and new guidelines from 2003 required that other materials than dental amalgam should be considered as the first choice in tooth fillings. Preventive use of fluoride has also contributed to improved dental health and reduced use of dental amalgam.
A requirement to have an approved dental amalgam separator installed in all dental clinics was introduced in 1994. Requirements to control the mercury air emissions from crematoria with more than 200 cremations per year were implemented in 2007.
Norway introduced a general ban on the use of mercury in products from 2008. Limited exemptions for dental amalgam use were applied until the end of 2010.”

“Dental amalgam is a metallic restorative material that is used for direct filling of carious lesions since many years. The use of this material generates solid and particulate wastes that present potential challenges to the environment. This study was carried out to assess amalgam use and waste management protocols practiced by Moroccan and Burkinabe dentists. A cross-sectional study was made of 79 in Rabat, Sale and Temara in Morocco and 56 in Ouagadougou, Bobo-Dioulasso in Burkina-Faso. The results showed that 69.5% of dental amalgam waste in Morocco vs 49.9% in Burkina-Faso was disposed with household waste which is a problem for both the environment and a risk to human being. Proper methods of dental amalgam waste disposal should be carried out to prevent indirect mercury poisoning for human.”