Mercury

“BACKGROUND/AIMS:

The homeostasis of essential metals such as copper, iron, selenium and zinc may be altered in the brain of subjects with Alzheimer’s disease (AD).

METHODS:

Concentrations of metals (magnesium, calcium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, tin, antimony, cesium, mercury and lead) were determined in plasma and cerebrospinal fluid (CSF) by inductively coupled plasma mass spectrometry in 173 patients with AD and in 87 patients with the combination of AD and minor vascular components (AD + vasc). Comparison was made with 54 healthy controls.

RESULTS:

The plasma concentrations of manganese and total mercury were significantly higher in subjects with AD (p < 0.001) and AD + vasc (p <or= 0.013) than in controls. In CSF, however, the concentrations of vanadium, manganese, rubidium, antimony, cesium and lead were significantly lower among subjects with AD (p <or= 0.010) and AD + vasc (p <or= 0.047) than in controls. Strong positive correlations were noted between plasma Cs versus CSF Cs in subjects with AD (r(s) = 0.50; p < 0.001), and AD + vasc (r(s) = 0.68; p < 0.001).

CONCLUSION:

Besides the raised plasma mercury concentrations, no consistent metal pattern in plasma or CSF was observed in patients with AD.”

OBJECTIVES:
Human blood levels of mercury are commonly 10nM, but may transiently reach 50-75nM after dental amalgam placement or removal. Controversy persists about the use of mercury because the effects of these ‘trace’ levels of mercury are not clear. Concentrations of mercury > or =5000nM unequivocally alter redox balance in blood cells including monocytes. In the current study, we tested a hypothesis that concentrations of mercury <100nM altered levels and activities of key proteins that maintain monocytic redox balance.

METHODS:
Human THP1 monocytes were exposed to 10-75nM of Hg(II) for 6-72h, with or without activation by lipopolysaccharide (LPS). The redox management proteins Nrf2 and thioredoxin-1 (Trx1) were separated by electrophoresis, then quantified by immunoblotting. The activity of the seleno-enzyme thioredoxin reductase (TrxR1), important in maintaining Trx1 redox balance, was measured by cell-free and cell-dependent assays.

RESULTS:
Concentrations of Hg(II) between 10-75nM increased Nrf2 levels (3.5-4.5 fold) and decreased Trx1 levels (2-3 fold), but these changes persisted <24h. Hg(II) potently inhibited (at concentrations of 5-50nM) TrxR1 activity in both cell-free and intracellular assays. Furthermore, Hg(II) transiently amplified LPS-induced Nrf2 levels by 2-3 fold and limited LPS-induced decreases in Trx1. All effects of Hg(II) were mitigated by pre-adding N-acetyl-cysteine (NAC) or sodium selenide (Na2SeO3), supplements of cellular thiols and selenols, respectively.

SIGNIFICANCE:
Our results suggest that nanomolar concentrations of Hg(II) transiently alter cellular redox balance in monocytes that trigger changes in Nrf2 and Trx1 levels. These changes indicate that monocytes have a capacity to adapt to trace concentrations of Hg(II) that are introduced into the bloodstream after dental amalgam procedures or fish consumption. The ability of monocytes to adapt suggests that low levels of mercury exposure from dental amalgam may not overtly compromise monocyte function.

“Children may be at particular risk from toxic effects of mercury (Hg). Previous studies of hair (organic) and urine (inorganic) Hg levels in US children were unable to assess Hg levels while accounting for exposure to amalgam dental restorations. This analysis describes, over a 5-year period, levels and correlates/predictors of scalp hair (H-Hg) and urinary (U-Hg) mercury in 534 New England Children’s Amalgam Trial (NECAT) participants, aged 6-10 years and without exposure to dental amalgam at baseline.
RESULTS:

Mean H-Hg levels were between 0.3 and 0.4 microg/g over 5 years. 17-29% of children had H-Hg levels > or = 0.5 microg/g, and 5.0 to 8.5% of children had levels > or = 1 microg/g, in any given study year. In adjusted models, fish consumption frequency was the most robust predictor of high H-Hg. U-Hg mean levels were between 0.7 and 0.9 microg/g creatinine over two years. The percentage of those with U-Hg > or 2.3 microg/g creatinine ranged from 4% to 6%. Number of amalgam restorations had a significant dose-response relationship with U-Hg level. Daily gum chewing in the presence of amalgam was associated with high U-Hg.”

“Mercury is toxic to the kidney, and dental amalgam is a source of mercury exposure. Few studies have evaluated the effects of dental amalgam on kidney function in a longitudinal context in children. Here, we evaluated urinary concentrations of glutathione S-transferases (GSTs) alpha and pi as biomarkers of renal proximal and distal tubular integrity, respectively, and albumin as a biomarker of glomerular integrity in children and adolescents 8-18 years of age over a 7-year course of dental amalgam treatment. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral and renal effects of dental amalgam in children. Subjects were randomized to either dental amalgam or resin composite treatments. Urinary GSTs alpha and pi, albumin, and creatinine concentrations were measured at baseline and annually in all subjects. Results were evaluated using linear regression analysis. GST-alpha concentrations were similar between treatment groups and in each sex and race (white vs. non-white) group in each follow-up year. GST-pi levels tended upward over the course of follow-up by four- to six-fold. This increase was seen in all groups irrespective of the treatment, race, or gender. Females had GST-pi levels approximately twice those of males at all ages. Albumin concentrations were constant throughout the follow-up period and did not differ by treatment, although females had 39% higher albumin levels than males. Additionally, we found no significant effects of amalgam treatment on the proportion of children with microalbuminuria (>30 mg/g creatinine). These findings are relevant within the context of children’s health risk assessment as relates to the safety of mercury exposure from dental amalgam on kidney function. These data also provide normative values for sensitive indices of renal functional integrity that may serve in the evaluation of children and adolescents with renal disorders.”

“There is a long running debate about whether or not dental amalgams represent a serious health hazard because of the mercury they contain. A scientific opinion produced for the European Commission has recommended a solution to the conundrum and provides some lessons for other medical device related causation issues.”

“A superantigen or autoimmunity has been hypothesized to be the main cause of the Kawasaki’s Disease but the etiology is unknown. Medical literature, epidemiological findings, and some case reports have suggested that mercury may play a pathogenic role. Several patients with Kawasaki’s Disease have presented with elevated urine mercury levels compared to matched controls. Most symptoms and diagnostic criteria which are seen in children with acrodynia, known to be caused by mercury, are similar to those seen in Kawasaki’s Disease. Genetic depletion of glutathione S-transferase , a susceptibility marker for Kawasaki’s Disease, is known to be also a risk factor for acrodynia and may also increase susceptibility to mercury . Coinciding with the largest increase (1985-1990) of thimerosal (49.6% ethyl mercury) in vaccines, routinely given to infants in the U.S. by 6 months of age (from 75microg to 187.5microg), the rates of Kawasaki’s Disease increased ten times, and, later (1985-1997), by 20 times. Since 1990 88 cases of patients developing Kawasaki’s Disease some days after vaccination have been reported to the Centers of Disease Control (CDC) including 19% manifesting symptoms the same day. The presented pathogenetic model may lead to new preventive- and therapeutic strategies for Kawasaki’s disease.”

“INTRODUCTION:

Stevens-Johnson syndrome (SJS) is an uncommon and potentially serious mucocutaneous disease. The most important step in the management of SJS is early recognition and immediate withdrawal of the causative agent. We present a patient with SJS associated with dimercaptopropane-1-sulfonate (DMPS) therapy.

CASE REPORT:

An asymptomatic 11-year old boy who had been exposed chronically to mercury vapour had a 24-hour urine mercury concentration of 37 microgram/L (reference value <10 microgram/L). Exposure to the mercury vapour was stopped and treatment with oral DMPS was begun. After two weeks of therapy, he developed a disseminated cutaneous eruption of red pruritic macules on his chest and back, which three days later had spread all over his body with the discrete maculae becoming confluent; erosions and crusts developed on his lips and he had blisters in his mouth. The diagnosis of SJS was made, the DMPS was stopped, and the SJS resolved gradually.

DISCUSSION:

Chelation agents like DMPS or DMSA are increasingly used and are available over the counter in some countries. These drugs are used in patients with complaints that are attributed to mercury-containing dental amalgams and in children with autism.

CONCLUSION:

The reported association suggests that SJS may be a potential complication of DMPS therapy, and this should be considered in the risk-benefit analysis of chelation.”

“For more than a decade the I.A.O.M.T. has been concerned with the environmental impact of dental amalgam mercury because of its extreme toxicity. Environmental scientists label it a ‘Persistent Bioaccumulative Toxin’ (PBT), and as such it is important to reduce it from the environment by eliminating its source, wherever possible.”

“BACKGROUND:
Many formulations of Thimerosal (49.55% mercury by weight)-containing Rho(D) immune globulins (TCRs) were routinely administered to Rh-negative mothers in the US prior to 2002.

OBJECTIVES:
It was hypothesized: (1) if prenatal Rho(D)-immune globulin preparation exposure was a risk factor for neurodevelopmental disorders (NDs) then more children with NDs would have Rh-negative mothers compared to controls; and (2) if Thimerosal in the Rho(D)-immune globulin preparations was the ingredient associated with NDs, following the removal of Thimerosal from all manufactured Rho(D)-immune globulin preparations from 2002 in the US the frequency of maternal Rh-negativity among children with NDs should be similar to control populations.

METHODS:
Maternal Rh-negativity was assessed at two sites (Clinic A-Lynchburg, VA; Clinic B-Rockville and Baltimore, MD) among 298 Caucasian children with NDs and known Rh-status. As controls, maternal Rh-negativity frequency was determined from 124 Caucasian children (born 1987-2001) without NDs at Clinic A, and the Rh-negativity frequency was determined from 1,021 Caucasian pregnant mothers that presented for prenatal genetic care at Clinic B (1980-1989). Additionally, 22 Caucasian patients with NDs born from 2002 onwards (Clinics A and B) were assessed for maternal Rh-negativity.

RESULTS:
There were significant and comparable increases in maternal Rh-negativity among children with NDs (Clinic: A=24.2%), autism spectrum disorders (Clinic: A=28.3%, B=25.3%), and attention-deficit-disorder/attention-deficit-hyperactivity-disorder (Clinic: A=26.3%) observed at both clinics in comparison to both control groups (Clinic: A=12.1%, B=13.9%) employed. Children with NDs born post-2001 had a maternal Rh-negativity frequency (13.6%) similar to controls.

CONCLUSION:
This study associates TCR exposure with some NDs in children.”

“Mercury, as any other heavy metal, may cause environmental damages due to its accumulation and biotransformation. Dental offices, whether private or institutional, use dental amalgam as a restorative material on a daily basis. Dental amalgam is composed of mercury (50%), silver (30%) and other metals. Approximately 30% of the amalgam prepared in dental offices (0.6 g per capsule) are wasted and inadequately discarded without any treatment. Methods for mercury recovery have been proposed previously, using high temperatures through exposure to direct flame (650 degrees C), long processing time, and hazardous reagents as potassium cyanide. The purpose of this study was to develop a method to replace the direct flame by an electrical mantle in the process of mercury recovery. Results showed an average mercury recovery of 90% from 2 kg of amalgam after 30 minutes of processing time, thus optimizing the procedure. The proposed modifications allowed a significant reduction in processing time and a mercury recovery with high purity. The modified process also provided minimization of operator exposure to physical, chemical and ergonomic hazards, representing a technological advance compared to the risks inherent to the original method. It also provided environmental health and economy of energy resources by replacing a finite energy source (fossil and organic) by a more environmentally appropriate electric source, resulting in significant improvement of the procedure for mercury recovery from dental amalgam.”