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“Several cases of skin sensitization have been reported following the application of thimerosal, which is composed of ethyl mercury and thiosalicylic acid (TSA). However, few in vitro studies have been carried out on human dendritic cells (DCs) which play an essential role in the initiation of allergic contact dermatitis. The aim of the present study was to identify the effect of thimerosal and other mercury compounds on human DCs. To address this purpose, DCs derived from monocytes (mono-DCs) were used. Data show that thimerosal and mercury derivatives induced DC activation, as monitored by CD86 and HLA-DR overexpression associated with the secretion of tumor necrosis factor alpha and interleukin 8, similarly to lipopolysaccharide and the sensitizers, 1-chloro-2,4-dinitrobenzene (DNCB) and nickel sulfate, which were used as positive controls. In contrast, TSA, the non-mercury part of thimerosal, as well as dichloronitrobenzene, a DNCB negative control, and the irritant, sodium dodecyl sulfate, had no effect. Moreover, oxidative stress, monitored by ROS induction and depolarization of the mitochondrial membrane potential, was induced by thimerosal and mercury compounds, as well as DNCB, in comparison with hydrogen peroxide, used as a positive control. The role of thiol oxidation in the initiation of mono-DC activation was confirmed by a pre-treatment with N-acetyl-l-cysteine which strongly decreased chemical-induced CD86 overexpression. These data are in agreement with several clinical observations of the high relevance of thimerosal in patch-test reactions and prove that human mono-DCs are useful in vitro tools for determining the allergenic potency of chemicals.”

“The aim was to report on the longevity of restorations placed using the atraumatic restorative treatment (ART) approach compared with that of equivalent placed amalgam restorations. Five databases were systematically searched for articles up to 16 March 2009. Inclusion criteria: (1) titles/abstracts relevant to the topic; (2) published in English; (3) reporting on 2-arm longitudinal in vivo trials; (4) minimum follow-up period of 12 months. Exclusion criteria: (1) insufficient random or quasi-random allocation of study subjects; (2) not all entered subjects accounted for at trial conclusion; (3) subjects of both groups not followed up in the same way. Fourteen from the initial search of 164 articles complied with these criteria and were selected for review. From these, seven were rejected and seven articles reporting on 27 separate datasets, accepted. Only identified homogeneous datasets were combined for meta-analysis. From the 27 separate computable dichotomous datasets, four yielded a statistically significant improvement of longevity of ART versus amalgam restorations: posterior class V, 28% over 6.3 years; posterior class I, 6% after 2.3 years and 9% after 4.3 years; posterior class II, 61% after 2.3 years. Studies investigating restorations placed in the primary dentition showed no significant differences between the groups after 12 and 24 months. In the permanent dentition, the longevity of ART restorations is equal to or greater than that of equivalent amalgam restorations for up to 6.3 years and is site-dependent. No difference was observed in primary teeth. More trials are needed in order to confirm these results.”

“In recent years, the cremation ratio of cadavers has increased dramatically in many countries. Crematories have been identified as sources of various environmental pollutants, being polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and mercury those raising most concern. In contrast to other incineration processes for which the number of studies on their toxic emissions is considerable, references related to PCDD/F and mercury emissions from crematories and their health risks are very limited. In this paper, the scientific information concerning these issues, using the databases PubMed, Scopus and Scirus, is reviewed. Results show that in comparison with PCDD/F emissions from other sources, those corresponding to crematories are significantly lower, while those of mercury should not be underrated.”

“An association between autism and early life exposure to mercury is a hotly debated issue. In this study, 91 autistic Polish children, male and female, 3-4 and 7-9 years old, were compared to 75 age- and sex-matched healthy children with respect to: demographic, perinatal, clinical and developmental measures, parental age, birth order, morphometric measures, vaccination history, and hair mercury content. In demographic and perinatal measures there were no consistent differences between the autistic and control groups. Autistic children had a significantly greater prevalence of adverse reactions after vaccinations and abnormal development than controls. Between 45 and 80% of autistic children experienced developmental regress. Autistic children significantly differed from healthy peers in the concentrations of mercury in hair: younger autistics had lower levels, while older – higher levels than their respective controls. The results suggest that autistic children differ from healthy children in metabolism of mercury, which seems to change with age.”

“BACKGROUND:

Detoxification is an essential process in all living organisms. Humans accumulate heavy metals primarily as a result of lifestyle and environmental contamination. However, not all humans experience the estimated individual exposure. This suggests the presence of genetic regulatory mechanisms.

OBJECTIVE:

In order to identify genetic factors underlying the inter-individual variance in detoxification capacity for the heavy metal mercury, 192 students were investigated. We focused on the relationship between polymorphisms in glutathione-S-transferase (GST) genes and mercury concentrations in blood, urine, and hair. The correlation between blood mercury levels, GSTT1 and GSTM1 polymorphism, and gene expression of certain metallothionein subgroups (MT1, MT3) was evaluated in a further group of students (N=30).

METHODS:

Mercury levels in acid digested samples were measured by cold vapor AAS. Genotyping of the GSTT1 and GSTM1-gene deletion polymorphism was performed by means of PCR. Gene expression of several MT genes was analyzed in lymphocytes from fresh peripheral blood by semiquantitative RT-PCR.

RESULTS:

The following was noted: a) hair mercury concentrations are significantly increased in persons with the double deleted genotype (GSTT1-/- and GSTM1-/-) as compared to persons with the intact genotype, and b) MT1X expression is higher in persons with the intact genotype (GSTT1+/+ and GSTM1+/+).

CONCLUSIONS:

We conclude that the epistatic effect of the GSTT1 and the GSTM1 deletion polymorphism is a risk factor for increased susceptibility to mercury exposure. The relationship between MT gene expression and GST gene polymorphisms needs further investigation. If MT expression depends on GST polymorphisms it would have important implications on the overall metal detoxification capability of the human organism.”

“OBJECTIVE:

The heavy metals lead (Pb) and mercury (Hg) are ubiquitous environmental pollutants with high neurotoxic potential. We aimed to compare perinatal Pb and Hg concentrations and to explore the potential association between Pb and Hg exposure and newborn anthropometry.

STUDY DESIGN:

Pregnant women were recruited in 2005 at the General Hospital Vienna for participation in this longitudinal study. Pb and Hg concentrations were measured in maternal blood and hair, placenta, cord blood, meconium, and breast milk of 53 mother-child pairs by CV-AAS, GF-AAS, and HPLC-CV-ICPMS. We conducted bivariate analyses and categorical regression analysis (CATREG) to evaluate the determinants of Pb and Hg exposure, and of infant anthropometry.

RESULTS:

Median Pb and total Hg contents were low, i.e., 25 μg/L (maternal blood-Pb), 13 μg/L (cord blood-Pb), 0.7 μg/L (maternal blood-Hg), and 1.1 μg/L (cord blood-Hg). Hg levels in maternal and fetal tissues were frequently correlated (r>0.3, P<0.05, respectively). Regarding Pb, only maternal blood and cord blood concentrations correlated (P=0.043). Cord blood levels indicated higher Hg exposure but lower Pb exposure relative to maternal blood contents. Adjusted CATREG models indicated the significant predictors of birth length (placenta-Pb, gestational length, meconium-Pb), birth weight (placenta-Pb, gestational length, maternal blood-Pb), and head circumference (maternal education, maternal height). Besides one significant correlation between maternal hair Hg and birth length, the mercury levels were not associated with newborn anthropometry.

CONCLUSIONS:

Our data implicate that different modes of action may exist for placentar transfer of Pb and Hg as well as that low Pb exposure levels can result in lower birth weight. The findings related to newborn anthropometry need to be confirmed by the examination of larger study groups. Further research is needed to clarify the mechanisms of Pb and Hg transfer via the placenta, and to explore how prenatal Pb exposure is related to intrauterine growth.

“Thimerosal, a mercury derivative composed of ethyl mercury chloride (EtHgCl) and thiosalicylic acid (TSA), is widely used as a preservative in vaccines and cosmetic products and causes cutaneous reactions. Since dendritic cells (DCs) play an essential role in the immune response, the sensitization potency of chemicals was studied in vitro using U937, a human promyelomonocytic cell line that is used as a surrogate of monocytic differentiation and activation. Currently, this cell line is under ECVAM (European Center for the Validation of Alternative Methods) validation as an alternative method for discriminating chemicals. Thimerosal and mercury derivatives induced in U937 an overexpression of CD86 and interleukin (IL)-8 secretion similarly to 1-chloro-2,4-dinitrobenzene (DNCB), a sensitizer used as a positive control for DC activation. Non-sensitizers, dichloronitrobenzene (DCNB), TSA and sodium dodecyl sulfate (SDS), an irritant, had no effect. U937 activation was prevented by cell pretreatment with N-acetyl-L-cysteine (NAC) but not with thiol-independent antioxidants except vitamin E which affected CD86 expression by preventing lipid peroxidation of cell membranes. Thimerosal, EtHgCl and DNCB induced glutathione (GSH) depletion and reactive oxygen species (ROS) within 15 min; another peak was detected after 2h for mercury compounds only. MitoSOX, a specific mitochondrial fluorescent probe, confirmed that ROS were essentially produced by mitochondria in correlation with its membrane depolarization. Changes in mitochondrial membrane permeability induced by mercury were reversed by NAC but not by thiol-independent antioxidants. Thimerosal and EtHgCl also induced a calcium (Ca2+) influx with a peak at 3h, suggesting that Ca2+ influx is a secondary event following ROS induction as Ca2+ influx was suppressed after pretreatment with NAC but not with thiol-independent antioxidants. Ca2+ influx was also suppressed when culture medium was deprived of Ca2+ confirming the specificity of the measure. In conclusion, these data suggest that thimerosal induced U937 activation via oxidative stress from mitochondrial stores and mitochondrial membrane depolarization with a primordial effect of thiol groups. A cross-talk between ROS and Ca2+ influx was demonstrated.”

“AIM:
We studied the effect on neurodevelopment of infants who are exposed to thimerosal in tetanus-diphtheria (Td) vaccines during pregnancy.

METHODS:
We compared Gesell Developmental Schedules (GDS) of exclusive breastfed infants at 6 months born to mothers who received Td (1 to 3 doses) against those who were born to mothers who did not take such vaccines.

RESULTS:
Compared with the group of infants not exposed to ethylmercury in utero, the infants of exposed mothers showed no significant difference in neurodevelopment delays. Although there was a significant correlation between hair-Hg of mothers and hair-Hg of neonates (Spearman r = 0.353; p = 0.0011), there was no significant correlation between the level of in utero exposure to ethylmercury in Td vaccines and neonate’s hair-Hg concentrations (Spearman r = 0.060; p = 0.5922). However, regression analysis showed that GDS at 6 months was significantly associated with total mercury concentration of neonate’s hair but was not sensitive to the number of vaccines taken by the mother.

CONCLUSION:
Early neurodevelopment of exclusively breastfed infants is sensitive to in utero exposure to mercury, but maternal thimerosal exposure in tetanus-diphtheria vaccines per se cannot portend clinical neurodevelopment delays measured by GDS at 6 months.”

“BACKGROUND:

Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).

OBJECTIVES:

This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.

METHODS:

This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.

RESULTS:

Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.

CONCLUSIONS:

These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.”

“OBJECTIVES:

The purpose of this study was to evaluate the systemic mercury levels in urine of patients and dental school students caused by exposure to silver amalgam. It is currently believed that occupational exposure shows the highest rate of potential for poisoning by mercury. Dental professionals are part of that quota, introducing concerns regarding the handling of dental amalgam.

MATERIALS AND METHODS:

The study comprised 40 urine samples from 20 subjects, which were divided into four sampling groups: G1A (n = 10) composed of students before their first occupational contact; G1B (n = 10) composed of the same G1 students after their first contact; G2A (n = 10) composed of patients who needed to have dental restorations before amalgam removal; and G2B (n = 10) composed of patients who needed to have dental restoration after amalgam removal. Cold-vapor atomic absorption spectrophotometry (CVAAS) was used as the evaluation method.

RESULTS:

A statistically significant difference was found among dependent groups 1 and 2 (p = 0.0038), whereas mercury levels increased considerably after the first occupational contact of all subjects.

CONCLUSIONS:

Occupational exposure to dental amalgam poses a potential risk of increasing systemic mercury levels, although urine mercury levels in all the sample participants were below the limits of biologic tolerance.”