Mercury

BACKGROUND AND AIM:
Although mercury is involved in several immunological diseases, nothing is known about its implication in celiac disease. Our aim was to evaluate blood and urinary levels of mercury in celiac patients.

METHODS:
We prospectively enrolled 30 celiac patients (20 treated with normal duodenal mucosa and 10 untreated with duodenal atrophy) and 20 healthy controls from the same geographic area. Blood and urinary mercury concentrations were measured by means of flow injection inductively coupled plasma mass spectrometry. Enrolled patients underwent dental chart for amalgam fillings and completed a food-frequency questionnaire to evaluate diet and fish intake.

RESULTS:
Mercury blood/urinary levels were 2.4 ± 2.3/1.0 ± 1.4, 10.2 ± 6.7/2.2 ± 3.0 and 3.7 ± 2.7/1.3 ± 1.2 in untreated CD, treated CD, and healthy controls, respectively. Resulting mercury levels were significantly higher in celiac patients following a gluten-free diet. No differences were found regarding fish intake and number of amalgam fillings. No demographic or clinical data were significantly associated with mercury levels in biologic samples.

CONCLUSION:
Data demonstrate a fourfold increase of mercury blood levels in celiac patients following a gluten-free diet. Further studies are needed to clarify its role in celiac mechanism.

The majority of the heme-binding proteins possess a “heme-pocket” that stably binds to heme. Usually known as housekeeping heme-proteins, they participate in a variety of metabolic reactions (e.g., catalase). Heme also binds with lower affinity to the “Heme-Regulatory Motifs” (HRM) in specific regulatory proteins. This type of heme binding is known as exchangeable or regulatory heme (RH). Heme binding to HRM proteins regulates their function (e.g., Bach1). Although there are well-established methods for assaying total cellular heme (e.g., heme-proteins plus RH), currently there is no method available for measuring RH independent of the total heme (TH). The current study describes and validates a new method to measure intracellular RH. This method is based on the reconstitution of apo-horseradish peroxidase (apoHRP) with heme to form holoHRP. The resulting holoHRP activity is then measured with a colorimetric substrate. The results show that apoHRP specifically binds RH but not with heme from housekeeping heme-proteins. The RH assay detects intracellular RH. Furthermore, using conditions that create positive (hemin) or negative (N-methyl protoporphyrin IX) controls for heme in normal human fibroblasts (IMR90), the RH assay shows that RH is dynamic and independent of TH. We also demonstrated that short-term exposure to subcytotoxic concentrations of lead (Pb), mercury (Hg), or amyloid-β (Aβ) significantly alters intracellular RH with little effect on TH. In conclusion the RH assay is an effective assay to investigate intracellular RH concentration and demonstrates that RH represents ∼6% of total heme in IMR90 cells.

It is estimated that 5.5 Million North Americans suffer from varying degrees of Alzheimer’s disease (AD) and by the year 2050 it may be one in 85 people globally (100 Million). It will be shown that heavy metal toxicity plays a significant role in sporadic AD. Although current literature speaks to involvement of metal ions (via Fenton reaction), studies and reviewers have yet to link cellular events including known structural changes such as amyloid plaque development to this metal toxicity the way it is proposed here. Contrary to the current AD model which positions BACE1 (β-secretase) as an aberrant or AD-advancing enzyme, it is proposed herein that the neuron’s protective counteraction to this metal toxicity is, in fact, a justified increase in BACE1 activity and amyloid precursor protein (APP) processing to yield more secreted APP (sAPP) and β-amyloid peptide in response to metal toxicity. This new perspective which justifies a functional role for APP, BACE1 enzyme activity and the peptide products from this activity may at first appear to be counterintuitive. Compelling evidence, however, is presented and a mechanism is shown herein that validate BACE1 recruitment and the resulting β-amyloid protein as strategic countermeasures serving the cell effectively against neuro-impeding disease.

In addition, the more recent understanding of how TREM-2 mutations factor into inflammatory response has shed new light on how chronic inflammatory activity can escalate to uncontrolled systemic levels in a variety of inflammatory diseases from neurodegenerative, auto-inflammatory and autoimmune diseases. TREM-2 mutations represent yet another complicating element in these multigenic disease pathologies. This review takes us one step back to discuss basic pathological features of these neurodegenerative diseases known to us for some time. However, the objective is to discuss the possibility of related or linked mechanisms that may exist through these basic disease hallmarks that we often classify as absolute signatures of one disease. These new perspectives will be discussed in the context of a new paradigm for Alzheimer’s disease that implicates heavy metals as a primary cause. Plausible links between these distinctly different pathologies are presented showing intersections of their distinct pathologies that hinge on metal interactions.

“BACKGROUND:
The effects of chronic occupational exposure to elemental mercury (Hg(0)) are largely unknown. The objective was to evaluate the association of occupational Hg(0) exposure with multiple sclerosis (MS) and tremor.

METHODS:
The study included 13,906 dentists who attended the American Dental Association’s annual meeting over 24 years (1986-2007 and 2011-2012). Participants reported MS and tremor and provided urine specimens for Hg(0) analysis. The authors estimated mean Hg(0) exposures over time and used logistic regression to estimate the associations of 3 Hg(0) exposure measures with MS or tremor.

RESULTS:
Among participants, 0.18% reported MS and 1.24% reported tremor. Hg(0) exposure was not associated with MS (odds ratio [OR] per 191 micrograms per liter in cumulative Hg(0) exposure, 0.85; 95% confidence interval [CI], 0.39-1.85). Increased prevalent risk of tremor was found with exposure to both urinary Hg(0) exposure (OR, 1.10 [95% CI, 1.00-1.22]) and cumulative Hg(0) exposure among younger dentists (< 51 years; OR, 1.13 [95% CI, 1.05-1.22]). CONCLUSIONS: Occupational Hg(0) exposure in US dentists decreased over time and now is approaching that of the general population. Our results suggest a positive association between Hg(0) exposure and tremor."

According to an earlier SDPI study, reported in 2013, alarmingly high mercury levels were observed
in air (indoor as well as outdoor) at 11 of the 34 visited dental sites (17 dental teaching institutions, 7
general hospitals & 10 dental clinics) in five main cities of Pakistan. 88% of the sites indicated indoor
mercury levels in air above the USA EPA reference level of 300ng/m3. These very high levels of
mercury vapors in air were thought to be due to more than one reasons, including the use of liquid
mercury & non-mechanical mixing for mercury amalgam making and lack of environmentally sound
best practices for mercury emissions/releases control. SDPI study also showed general unawareness
among dental professionals regarding appropriate handling of mercury/mercury amalgam and
careless/care free use of mercury/mercury amalgam by the undergraduate students. A follow up
study was carried out in 2014, to review and evaluate the contents of Bachelor of Dental Surgery
(BDS) curriculum, offered to undergraduate students at dental teaching institutions in the country.
The objective of this study was to see whether or not, the curriculum provided adequate information
& training to upcoming dental professionals, regarding hazardous mercury/mercury amalgam use in
dentistry and mercury related issues.

“Environmental exposure to metal mixtures in the human population is common. Mixture risk assessments are often challenging because of a lack of suitable data on the relevant mixture. A growing number of studies show an association between lead or mercury exposure and cardiovascular effects. We investigated the cardiovascular effects of single metal exposure or co-exposure to methylmercury [MeHg(I)], inorganic mercury [Hg(II)] and lead [Pb(II)]. Male Wistar rats received four different metal mixtures for 28 days through the drinking water. The ratios of the metals were based on reference and environmental exposure values. Blood and pulse pressure, cardiac output and electrical activity of the heart were selected as end-points. While exposure to only MeHg(I) increased the systolic blood pressure and decreased cardiac output, the effects were reversed with combined exposures (antagonism). In contrast to these effects, combined exposures negatively affected the electrical activity of the heart (synergism). Thus, it appears that estimates of blood total Hg levels need to be paired with estimates of what species of mercury dominate exposure as well as whether lead co-exposure is present to link total blood Hg levels to cardiovascular effects. Based on current human exposure data and our results, there may be an increased risk of cardiac events as a result of combined exposures to Hg(II), MeHg(I) and Pb(II). This increased risk needs to be clarified by analyzing lead and Hg exposure data in relation to cardiac electrical activity in epidemiological studies. “

“In spite of numerous research efforts, the exact etiology of autoimmune diseases remains largely unknown. Genetics and environmental factors, including xenobiotics, are believed to be involved in the induction of autoimmune disease. Some environmental chemicals, acting as haptens, can bind to a high-molecular-weight carrier protein such as human serum albumin (HSA), causing the immune system to misidentify self-tissue as an invader and launch an immune response against it, leading to autoimmunity. This study aimed to examine the percentage of blood samples from healthy donors in which chemical agents mounted immune challenges and produced antibodies against HSA-bound chemicals. The levels of specific antibodies against 12 different chemicals bound to HSA were measured by ELISA in serum from 400 blood donors. We found that 10% (IgG) and 17% (IgM) of tested individuals showed significant antibody elevation against aflatoxin-HSA adduct. The percentage of elevation against the other 11 chemicals ranged from 8% to 22% (IgG) and 13% to 18% (IgM). Performance of serial dilution and inhibition of the chemical-antibody reaction by specific antigens but not by non-specific antigens were indicative of the specificity of these antibodies. Although we lack information about chemical exposure in the tested individuals, detection of antibodies against various protein adducts may indicate chronic exposure to these chemical haptens in about 20% of the tested individuals. Currently the pathological significance of these antibodies in human blood is still unclear, and this protein adduct formation could be one of the mechanisms by which environmental chemicals induce autoimmune reactivity in a significant percentage of the population.”

High-level exposures to a number of agents are known to have direct nephrotoxic effects in children. A growing body of literature supports the hypothesis that chronic, relatively low-level exposure to various nephrotoxicants may also increase the risk for chronic kidney disease (CKD) or accelerate its progression. In this review we highlight several environmental nephrotoxicants and their association with CKD in children and adolescents. We also discuss unique epidemiological challenges in the use of kidney biomarkers in environmental nephrotoxicology.

“Kidney disease disproportionately affects racial and ethnic minority populations, the poor, and the socially disadvantaged. The excess risk of kidney disease among minority and disadvantaged populations can only be partially explained by an excess of diabetes, hypertension, and poor access to preventive care. Disparities in the environmental exposure to nephrotoxicants have been documented in minority and disadvantaged populations and may explain some of the excess risk of kidney disease. High-level environmental and occupational exposure to lead, cadmium, and mercury are known to cause specific nephropathies. However, there is growing evidence that low-level exposures to heavy metals may contribute to the development of CKD and its progression. In this article, we summarize the excess risk of environmental exposures among minority and disadvantaged populations. We also review the epidemiologic and clinical data linking low-level environmental exposure to lead, cadmium, and mercury to CKD and its progression. Finally, we briefly describe Mesoamerican nephropathy, an epidemic of CKD affecting young men in Central America, which may have occupational and environmental exposures contributing to its development.”