Apolipoprotein-E (apo-E) genotyping has been investigated as an indicator of susceptibility to heavy metal (i.e., lead) neurotoxicity. Moreover, the apo-E epsilon (epsilon)4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A theoretical biochemical basis for this risk factor is discussed herein, supported by data from 400 patients with presumptive mercury-related neuro-psychiatric symptoms and in whom apo-E determinations were made. A statistically relevant shift toward the at-risk apo-E epsilon4 groups was found in the patients p<0.001). The patients possessed a mean of 13.7 dental amalgam fillings and 31.5 amalgam surfaces. This far exceeds the number capable of producing the maximum identified tolerable daily intake of mercury from amalgam. The clinical diagnosis and proof of chronic low-level mercury toxicity has been difficult due to the non-specific nature of the symptoms and signs. Dental amalgam is the greatest source of mercury in the general population and brain, blood and urine mercury levels increase correspondingly with the number of amalgams and amalgam surfaces in the mouth. Confirmation of an elevated body burden of mercury can be made by measuring urinary mercury, after provocation with 2,3,-dimercapto-propane sulfonate (DMPS) and this was measured in 150 patients. Apo-E genotyping warrants investigation as a clinically useful biomarker for those at increased risk of neuropathology, including AD, when subjected to long-term mercury exposures. Additionally, when clinical findings suggest adverse effects of chronic mercury exposure, a DMPS urine mercury challenge appears to be a simple, inexpensive procedure that provides objective confirmatory evidence. An opportunity could now exist for primary health practitioners to help identify those at greater risk and possibly forestall subsequent neurological deterioration.
http://www.ncbi.nlm.nih.gov/pubmed/12897404
And this:
Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.
http://www.ncbi.nlm.nih.gov/pubmed/8711748
This:
Some studies have shown higher mercury concentrations in brains of deceased and in blood of living patients with Alzheimer's disease. Experimental studies have found that even smallest amounts of mercury but no other metals in low concentrations were able to cause all nerve cell changes, which are typical for Alzheimer's disease. The most important genetic risk factor for sporadic Alzheimer's disease is the presence of the apolipoprotein Ee4 allele whereas the apolipoprotein Ee2 allele reduces the risk of developing Alzheimer's disease. Some investigators have suggested that apolipoprotein Ee4 has a reduced ability to bind metals like mercury and therefore explain the higher risk for Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/pubmed/15580166
And this:
We studied the effects of organic and inorganic mercury (Hg) on the uptake of L-[3H] glutamate (L-GLU) in cultured mouse astrocytes. Following exposure to mercuric chloride (MC) [0.2 approximately 5.0 microM], selective and dose-dependent inhibition of L-GLU uptake to 50% of control levels was observed, whereas 2-deoxyglucose (2-DG) uptake was not significantly affected. Methylmercuric chloride (MMC) also inhibited L-GLU uptake but 50% reduction was reached only at a concentration of 10 microM. Inhibition of L-GLU uptake by MMC appears to be closely linked to voltage-sensitive calcium channels as evidenced by the lack of L-GLU uptake inhibition by MMC in calcium-free medium or in the presence of the channel blocker verapamil. Exposure to a variety of divalent metallic ions, including CuCl2, FeCl2 and ZnCl2, did not affect L-GLU uptake in astrocytes in vitro. Exposure to PbCl2, however, resulted in a decline in L-GLU uptake, though to a much smaller degree than that observed with Hg compounds. Selective impairment of astroglial L-GLU transport may represent a critical early pathogenetic feature of Hg-induced neurotoxicity.
Toxicity of mercury depends on the type of mercury, route of entry into the body, your age at time of exposure, whether the exposure is repeated (even in low doses), your personal genetic makeup, including metabolism, pre-existing conditions and errors of immune function or excretion of metals, even your diet (I did read one saying certain vitamins reduces the toxicity of mercury). There are going to be a very high number of individuals, based on all these factors, for whom even tiny mercury exposures are not safe, therefore in my opinion it should not be used in medicines for the benefit of the whole population.
Comment Reply
Well, this government site says that unborn children are five to ten times more sensitive to mercury than adults:
http://www.usgs.gov/themes/factsheet/146-00/#environment
And this:
Apolipoprotein-E (apo-E) genotyping has been investigated as an indicator of susceptibility to heavy metal (i.e., lead) neurotoxicity. Moreover, the apo-E epsilon (epsilon)4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A theoretical biochemical basis for this risk factor is discussed herein, supported by data from 400 patients with presumptive mercury-related neuro-psychiatric symptoms and in whom apo-E determinations were made. A statistically relevant shift toward the at-risk apo-E epsilon4 groups was found in the patients p<0.001). The patients possessed a mean of 13.7 dental amalgam fillings and 31.5 amalgam surfaces. This far exceeds the number capable of producing the maximum identified tolerable daily intake of mercury from amalgam. The clinical diagnosis and proof of chronic low-level mercury toxicity has been difficult due to the non-specific nature of the symptoms and signs. Dental amalgam is the greatest source of mercury in the general population and brain, blood and urine mercury levels increase correspondingly with the number of amalgams and amalgam surfaces in the mouth. Confirmation of an elevated body burden of mercury can be made by measuring urinary mercury, after provocation with 2,3,-dimercapto-propane sulfonate (DMPS) and this was measured in 150 patients. Apo-E genotyping warrants investigation as a clinically useful biomarker for those at increased risk of neuropathology, including AD, when subjected to long-term mercury exposures. Additionally, when clinical findings suggest adverse effects of chronic mercury exposure, a DMPS urine mercury challenge appears to be a simple, inexpensive procedure that provides objective confirmatory evidence. An opportunity could now exist for primary health practitioners to help identify those at greater risk and possibly forestall subsequent neurological deterioration.
http://www.ncbi.nlm.nih.gov/pubmed/12897404
And this:
Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.
http://www.ncbi.nlm.nih.gov/pubmed/8711748
This:
Some studies have shown higher mercury concentrations in brains of deceased and in blood of living patients with Alzheimer's disease. Experimental studies have found that even smallest amounts of mercury but no other metals in low concentrations were able to cause all nerve cell changes, which are typical for Alzheimer's disease. The most important genetic risk factor for sporadic Alzheimer's disease is the presence of the apolipoprotein Ee4 allele whereas the apolipoprotein Ee2 allele reduces the risk of developing Alzheimer's disease. Some investigators have suggested that apolipoprotein Ee4 has a reduced ability to bind metals like mercury and therefore explain the higher risk for Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/pubmed/15580166
And this:
We studied the effects of organic and inorganic mercury (Hg) on the uptake of L-[3H] glutamate (L-GLU) in cultured mouse astrocytes. Following exposure to mercuric chloride (MC) [0.2 approximately 5.0 microM], selective and dose-dependent inhibition of L-GLU uptake to 50% of control levels was observed, whereas 2-deoxyglucose (2-DG) uptake was not significantly affected. Methylmercuric chloride (MMC) also inhibited L-GLU uptake but 50% reduction was reached only at a concentration of 10 microM. Inhibition of L-GLU uptake by MMC appears to be closely linked to voltage-sensitive calcium channels as evidenced by the lack of L-GLU uptake inhibition by MMC in calcium-free medium or in the presence of the channel blocker verapamil. Exposure to a variety of divalent metallic ions, including CuCl2, FeCl2 and ZnCl2, did not affect L-GLU uptake in astrocytes in vitro. Exposure to PbCl2, however, resulted in a decline in L-GLU uptake, though to a much smaller degree than that observed with Hg compounds. Selective impairment of astroglial L-GLU transport may represent a critical early pathogenetic feature of Hg-induced neurotoxicity.
Toxicity of mercury depends on the type of mercury, route of entry into the body, your age at time of exposure, whether the exposure is repeated (even in low doses), your personal genetic makeup, including metabolism, pre-existing conditions and errors of immune function or excretion of metals, even your diet (I did read one saying certain vitamins reduces the toxicity of mercury). There are going to be a very high number of individuals, based on all these factors, for whom even tiny mercury exposures are not safe, therefore in my opinion it should not be used in medicines for the benefit of the whole population.
October 4, 2011 - 3:09amThis Comment
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