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“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.”

“The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction.”

“Mercury (Hg) is a strong toxicant affecting mainly the central nervous, renal, cardiovascular and immune systems. Thiomersal (TM) is still in use in medical practice as a topical antiseptic and as a preservative in multiple dose vaccines, routinely given to young children in some developing countries, while other forms of mercury such as methylmercury represent an environmental and food hazard. The aim of the present study was to determine the effects of thiomersal (TM) and its breakdown product ethylmercury (EtHg) on thethioredoxin system and NADP(+)-dependent dehydrogenases of the pentose phosphate pathway. Results show that TM and EtHg inhibited the thioredoxin system enzymes in purified suspensions, being EtHg comparable to methylmercury (MeHg). Also, treatment of neuroblastoma and liver cells with TM or EtHg decreased cell viability (GI50: 1.5 to 20μM) and caused a significant (p<0.05) decrease in the overall activities of thioredoxin (Trx) and thioredoxin reductase (TrxR) in a concentration- and time-dependentmanner in cell lysates. Compared to control, the activities of Trx and TrxR in neuroblastoma cells after EtHg incubation were reduced up to 60% and 80% respectively, whereas in hepatoma cells the reduction was almost 100%. In addition, the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were also significantly inhibited by all mercurials, with inhibition intensity of Hg(2+)>MeHg≈EtHg>TM (p<0.05). Cell incubation with sodium selenite alleviated the inhibitory effects on TrxR and glucose-6-phosphate dehydrogenase. Thus, the molecular mechanism of toxicity of TM and especially of its metabolite EtHg encompasses the blockage of the electrons from NADPH via thethioredoxin system.”

“Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.”

“Methylmercury (MeHg) is a neurotoxicant and may have an adverse impact on child behavior. However, this impact was found to be inconsistent in fish-eating populations. Although the positive effects of the nutrients provided by a fish diet may overcome the effect of MeHg, the possibility of genetic variants influencing an individual’s response to MeHg has also been discussed. The role of the Apolipoprotein E (APOE) epsilon 4 allele (ε4) on MeHg related neurotoxicity is still unclear. In the present study, we investigated the role of APOE variants in the relationship between cord blood mercury (Hg) and child behavior. A total of 166 subjects were recruited at delivery, and their cord blood was collected for laboratory analyses of Hg and the APOE genotype. The Child Behavior Checklist (CBCL) was administered to the subjects when they reached the age of two years. An increase in cord blood Hg concentrations in APOE ε4 carriers was consistently associated with an increased score for all CBCL syndromes. After controlling for potential confounding factors, the group of ε4 carriers with an elevated cord blood Hg concentration had significantly higher scores in the syndrome categories of general internalizing, emotionally reactive, and anxiety/depression as well as CBCL total scores. Furthermore, general externalizing and aggressive syndromes were borderline significantly higher in this group. In conclusion, we suggest that APOE may modify the toxicity of MeHg. APOE ε4 carriers may be more vulnerable to the effects of MeHg on child behavior at the age of two years.”

“Thimerosal is an organic mercury (Hg)-containing compound (49.55 % Hg by weight) historically added to many multi-dose vials of vaccine as a preservative. A hypothesis testing case-control study evaluated automated medical records in the Vaccine Safety Datalink (VSD) for organic Hg exposure from Thimerosal in Haemophilus influenzae type b (Hib)-containing vaccines administered at specific times within the first 15 months of life among subjects diagnosed with pervasive developmental disorder (PDD) (n?=?534) in comparison to controls. The generally accepted biologically non-plausible linkage between Thimerosal exposure and subsequent diagnosis of febrile seizure (n?=?5886) was examined as a control outcome. Cases diagnosed with PDD received significantly more organic Hg within the first 6 months of life (odds ratio (OR)?=?1.97, p?<?0.001) and first 15 months of life (OR?=?3.94, p?<?0.0001) than controls, whereas cases diagnosed with febrile seizure were no more likely than controls to have received increased organic Hg. On a per microgram of organic Hg basis, cases diagnosed with a PDD in comparison to controls were at significantly greater odds (OR?=?1.0197, p?<?0.0001) of receiving increasing organic Hg exposure within the first 15 months of life, whereas cases diagnosed febrile seizure were no more likely than controls (OR?=?0.999, p?>?0.20) to have received increasing organic Hg exposure within the first 15 months of life. Routine childhood vaccination is an important public health tool to reduce the morbidity and mortality associated with infectious diseases, but the present study provides new epidemiological evidence of a significant relationship between increasing organic Hg exposure from Thimerosal-containing vaccines and the subsequent risk of PDD diagnosis in males and females.”

“BACKGROUND:
In vaccines/biologics, preservatives are used to prevent microbial growth.

MATERIAL/METHODS:
The present study examined: (1) the comparative toxicities of commonly used preservatives in US licensed vaccines to human neurons; and (2) the relative toxicity index of these compounds to human neurons in comparison to bacterial cells.

RESULTS:
Using human neuroblastoma cells, the relative cytotoxicity of the levels of the compounds commonly used as preservative in US licensed vaccines was found to be phenol <2-phenoxyethanol < benzethonium chloride < Thimerosal. The observed relative toxicity indices (human neuroblastoma cells/bacterial cells) were 2-phenoxyethanol (4.6-fold) < phenol (12.2-fold) < Thimerosal (>330-fold). In addition, for the compounds tested, except for 2-phenoxyethanol, the concentrations necessary to induce significant killing of bacterial cells were significantly higher than those routinely present in US licensed vaccine/biological preparations.

CONCLUSIONS:
None of the compounds commonly used as preservatives in US licensed vaccine/biological preparations can be considered an ideal preservative, and their ability to fully comply with the requirements of the US Code of Federal Regulations (CFR) for preservatives is in doubt. Future formulations of US licensed vaccines/biologics should be produced in aseptic manufacturing plants as single dose preparations, eliminating the need for preservatives and an unnecessary risk to patients.”

“The effect of mercury compounds has been tested on the organic cation transporter, hOCTN1. MeHg(+), Hg(2+), or Cd(2+) caused strong inhibition of transport. 1,4-Dithioerythritol (DTE), cysteine (Cys), and N-acetyl-l-cysteine reversed (NAC) the inhibition at different extents. 2-Aminoethyl methanethiosulfonate hydrobromide (MTSEA), a prototype SH reagent, exerted inhibition of transport similar to that observed for the mercurial agents. To investigate the mechanism of action of mercurials, mutants of hOCTN1 in which each of the Cys residues was substituted by Ala have been constructed, over-expressed in Escherichia coli, and purified. Tetraethylammonium chloride (TEA) uptake mediated by each mutant in proteoliposomes was comparable to that of wild type (WT). IC50 values of the WT and mutants for the mercury compounds were derived from dose-response analyses. The mutants C50A and C136A showed significant increase of IC50 indicating that the 2 Cys residues were involved in the interaction with the mercury compounds and inhibition of the transporter. The double mutant C50A/C136A was constructed; the lack of inhibition confirmed that the 2 Cys residues are the targets of mercury compounds. MTSEA showed similar behavior with respect to the mercurial reagents with the difference that increased IC50 was observed also in the C81A mutant. Similar results were obtained when transport was measured as acetylcholine uptake. Ethyl mercury (Thimerosal) inhibited hOCTN1 as well. C50A, C50A/C136A and, at very lower extent, C136A showed increased IC50 indicating that C50 was the major target of this mercury compound. The homology model of hOCTN1 was built using as template PiPT and validated by the experimental data on mutant proteins.”

Author:
Rossi G, Vallesi G, Srl SS, Terni IC, Raggi F, Giustozzi M.

Comment:
The researchers conclude, “Our result could be related to the decreasing of mercury in HMA, since many studies show a possible link between MS and mercury. According to our opinion, this report indicates that effort in research should be implemented to better understand possible links between heavy metals intoxication, MS and cancer events. Furthermore, based on a reliable test HMA and on a specific vitamin and mineral integration, we expect that more studies will be performed on this new field.”

Abstract/Excerpt:
“Male, 34 years old, European ethnic. He started having symptoms in 1999 while the Relapsing-Remitting MS was diagnosed in 2004. In May 2007, the patient underwent his first Hair Mineral Analysis, showing mercury and aluminium excess. After the first 6 months of dietary integration based on Hair Mineral Analysis (HMA) results, the patient noticed increasing of the strength, physical endurance, more energy, beside the disappearance of headache and other symptoms. Evaluation by MRI reported the reduction of the ‘amount of encephalic lesions’ and of the ‘extension of the lesion located in the left near-trigonous white matter’; as well, ‘numerous plaques within the periventricular white matter in front-parietal region, bilaterally’ disappeared. To date, symptoms are slowly but constantly decreasing. Concomitant HMA control shown a clear decreasing of mercury.”

Citation:
Rossi G, Vallesi G, Srl SS, Terni IC, Raggi F, Giustozzi M. A case report of dietary integration therapy based on hair mineral analysis slows the progression of multiple sclerosis. Implication for cancer prevention. Issues. 2015; 2(1): 14.

Country of origin:
Italy