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MERCURY, SCIENCE AND POLITICS. January 2008 Dr. Boyd Haley Professor of Chemistry/Biochemistry University of Kentucky. VISUALIZATION OF MERCURY EMITTING FROM A DENTAL AMALGAM. From: www. uninformed concent.com David Kennedy’s IAOMT tape
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MERCURY, SCIENCE AND POLITICS January 2008 Dr. Boyd Haley Professor of Chemistry/Biochemistry University of Kentucky
VISUALIZATION OF MERCURY EMITTING FROM A DENTAL AMALGAM • From: www. uninformed concent.com • David Kennedy’s IAOMT tape IN SPITE OF THE OBVIOUS EMISSION OF Hg VAPORS FROM DENTAL AMALGAM THE FDA HAS STEADFASTLY REFUSED TO TEST THEM FOR SAFETY!
Mercury from Dental Amalgam Pro-amalgam ADA spokespersons “estimate” that about 0.03 mcg mercury are emitted from a single amalgam per day. Estimate that it would take several hundred amalgams to provide a toxic exposure. A new IAOMT study shows that different amalgam types emit more mercury and that a single spill (very small amalgam) emits between 4.0 to 20 mcg of mercury per day at room temperature and without abrasion of any sort. This is about 133 to 666 times more than was estimated by the ADA!
IAOMT AMALGAM STUDY PROCEDURE • Nine dentists across the USA volunteered to make 10 cylindrical, one spill amalgams in a provided plexiglass mold. • The IAOMT provided new amalgam kits directly from the manufacturers to each dentist. • The amalgams in the molds were sent to Dr. Haley at the University of Kentucky for Hg analysis. • The amalgams were allowed to age for over one month to eliminate any surface mercury. • The amalgams were placed in 10 ml of distilled water which was changed daily. • Aliquots of this water were removed at days indicated and analyzed for mercury content.
Literature • 0.54 µg/g Hg in feces when amalgams are present. This is 540ng/g (see next slide!) • Daily excretion in feces 60 µg of Hg Determined and Presented by Dr. David Quig of Doctor’s Data, USA
ELEVATED MERCURY IN IDIOPATHIC DILATED CARDIOMYOPATHY (IDCM).WHERE DOES THE Hg COME FROM? LEVELS ng/g Hg Sb Controls 8.0 1.5 IDCM 178,400 19.260 Frustaci et al., J. of American College of Cardiology, 33, (6) 1578, 1999. Controls were patients with valvular or ischemic heart disease. ATHLETIC YOUTH DIE OF IDCM. WHY HASN’T NIH REQUESTED PROPOSALS FOR RESEARCH TO STUDY THIS?? THIS IS PROOF THAT MERCURY CAN CONCENTRATE IN SPECIFIC TISSUES OR ORGANS OF THE BODY, EVEN IF Hg BLOOD LEVELS ARE FOUND TO BE IN THE NORMAL RANGE.
? DeRouen et al. JAMA 295, 1784-92, 2006
GIRLS BOYS J. Woods, et al., Environmental Health Perspectives (2007) 115;10, 1527-1531.
The previous slide shows that prolonged exposure to mercury vapor decreases the child’s ability to excrete mercury through their kidneys. Especially affects BOYS. • This is consistent with the well known toxic effects of mercury on kidneys. • This explanation is consistent with the reports by the EPA and National Academy of Sciences that 8 to10% of American women have such high Hg body levels that would render increased susceptibility to neurological damage any child they would give birth to.
Activated Matrix Metallo Proteinase (MMP) is involved in numerous inflammatory diseases. Our new research shows MMP is activated by mercury and organic mercury! Atrial fibrillation (AF) produces changes in atrial structure and extracellular matrix composition, which is regulated by matrix metalloproteinases (MMPs) and often occurs in the setting of congestive heart failure. Matrix metalloproteinases (MMPs) are thought to participate in the pathogenesis of coronary artery disease (CAD), particularly in the occurrence of acute coronary syndrome (ACS). Matrix metalloproteases (MMPs) are important in many physiological processes including development, reproduction, and wound repair. Conversely, aberrant MMPs expression can be detrimental, promoting the pathologic destruction of extracellular matrix components in numerous disease states including breast and squamous cell carcinoma. The significance of circulating matrix metalloproteinases -2 and -9 (MMP-2, MMP-9), as well as their tissue inhibitors -1 and -2 (TIMP-1, TIMP-2) in ovarian cancer were studied to assess the possibility of using them in clinical decision-making. Within malignant neoplasias, high circulating TIMP-1 correlated to the aggressive phenotype and unfavorable prognosis. Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of diseases such as Alzheimer's Disease (AD) and amyotrophic lateral sclerosis (ALS). Increased expression of MMP-9 and TIMPs has been reported in postmortem AD and ALS brain tissue, as well as in ALS cerebrospinal fluid (CSF) and plasma. In active MS patients, both with relapsing-remitting and chronic progressive disease MMP-9 mRNA and plasma protein levels were significantly increased compared to healthy controls. Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes are mediated by increased levels of endogenous metalloproteinases (MMPs) within the aorta. These data suggest that the balance of MMP-2 and MMP-9 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of renal cell carcinoma. Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently MMP-inhibitors have entered clinical trials. The obtained results support the hypothesis that MMPs and their endogenous inhibitors participate in the invasive process of human osteosarcoma. NUMEROUS DISEASES INCLUDING SEVERAL CANCERS AND NEUROLOGICAL ILLNESSES ARE ASSOCIATED WITH THE ACTIVATION OF SPECIFIC MATRIX METALLO PROTEINASES (MMP). Hg2+ AND ETHYL-Hg BOTH ACTIVATE A COMMON FORM OF MMP.
BOTH Hg2+ AND THIMEROSAL ACTIVATE MMP-9, AN ENZYME THAT DIGESTS COLLAGEN AND LEADS TO TISSUE BREAKDOWN.
Results: Digestion of collagen by MMP-9 was greatly enhanced by preincubation with Hg2+, PMA and Thimerosal. Kinetics and concentration effect studies are continuing. A polyacrylamide gel on which collagen and its peptides have been separated after incubation with MMP-9 with and without preincubation of the enzyme with Hg2+ , PMA or thimerosal. 1. Hagele, et al. Mercury Activates Vascular Endothelial Cell Phospholipase-D through Thiols and Oxidative Stress. Inter. J. of Toxicology (2007) 26:57-69. 2.Ionescu, J. G. et al. Increased Levels of Transition Metals in Breast Cancer Tissue. Neuroendocrinology Letters (2006) 27:1, 36-39.
Hg2+ and Thimerosal activate MMP-9. This activation may be inhibited by compounds that chelate Hg2+.
Axonal Transport - A Process Essential for the Survival of Neurons Dendrite Membrane Bound Organelle Axon Dynien Microtubule Kinesin
HgEDTA Induces Aberrant [32P]8N3GTP-ß-Tubulin Interactions Indicative of AD Normal Brain without and with Hg2+. Alzheimer’s Disease Brain
EDTA Prevents Cd, Cu & Zn But Not Hg Inhibition of [32P]8N3GTP Photolabeling of Brain ß-Tubulin
SEQUENTIAL AMALGAM EXTRACTION SOLUTIONS INHIBIT THE VIABILITY OF BRAIN TUBULIN % Active Hours of Amalgam Soak
Effect of treating neurons in culture with nanomolar levels of Hg2+. Leong et al. University of Calgary
Immunostaining for Tubulin in Neurons treated with Hg2+. Leong et al. University of Calgary.
INHIBITION OF CREATINE KINASE (CK) BY WATER EXPOSED TO AGED AMALGAM . CK IS 97% INHIBITED IN ALZHEIMER’S DISEASED BRAIN. Amalgam soak time. ASSAY TIME MINUTES RELATIVE LEVEL [32P]-CREATINE PHOSPHATE PRODUCED
Pink Disease/Acrodynia • Affected 1 in 500 children in late 1800s until about 1940. • Cause was mercurous chloride (calomel) in teething powers. • Elimination of these mercury containing teething powders eliminated this disease. • Therefore, it is very plausible that low level exposure to mercury at an early age could cause a neurological disease. • Note: Ethylmercury is many times more toxic than mercurous chloride. Lethality is not an absolute measurement of all toxic effects.
Current Situation • Drugs use to treat behavioral disorders (autism, ADHD) has increased dramatically (369%) in the recent past to where we now spend more on these drugs than we do on antibiotics and asthma drugs for children. • The USA now spends more on drugs to treat ADHD than it does on antibiotics and asthma drugs. • 1 of 6 children in the USA have a diagnosed neurodevelopmental problem according to the CDC. About 1 in 166 have autism. • We have a major problem! • Yet, our FDA, CDC, NIH and AMA ignore the effects of dental and medical induced exposures to mercury.
Thimerosal Is Composed of Thiosalicylic Acid And Ethyl Mercury, A Known Neurotoxicant Water soluble Water insoluble • 1. The Merck Index, 12th ed., p. 1590, #9451 (1996). • 2. Martindale The Extra Pharmacopoeia, 30th ed., 804 (1993).
Organ Mercury Levels in Infants with Omophaloceles Treated with Thimerosal.Fagan et al. Archives of Disease in Childhood 52, 962-64, 1977 • Between 1969-75, 13 cases were treated, 10 died. Mercury analysis of organs ranged from 65 to 2,700 times normal levels. This appears to be from 9 to 48 topical applications of 0.1% thimerosal applications. NOTE; These children were most likely on antibiotics. Consider the effect on their immune system! • “Paradoxically, (in another study) 3 infants exposed postnatally (Iraq, Methyl-Hg by ingestion) did not exhibit signs or symptoms, though their blood levels were >1,000ppb, and one was >1,500ppb.” No antibiotics involved! Blood levels are not a measure of toxicity. • CONCLUSION IN 1977: “Organic mercurial antiseptics should be heavily restricted or withdrawn from hospital use, and the fact that mercury readily penetrates intact membranes and is highly toxic seems to have been forgotten.” Result: Merthiolate (thimerosal) was removed from the market by the FDA due to its inherent toxicity to infants.
RAPID BLOOD TO BRAIN MOVEMENT OF [203Hg]-THIMEROSAL:Gasset et al. Tetratogenicities of Opthalmic Drugs. Arch. Opthalomology 93, 52-55, 1975. • Pregnant rabbits were injected subcutaneous with [203Hg]-thimerosal. • From hour 1 post injection to hour 6 the cpm of 203Hg in the blood decreased from 100,000 to less than 25,000 cpm, or over 75%. • From hour 2 post injection to hour 6 there was increased cpm of 203Hg in the fetal brain (2 fold), liver (4 fold) and kidney (3 fold). • Yet the IOM/CDC/AAP states that the rapid loss of mercury from thimerosal from the blood makes it unlikely to be toxic enough to cause autism. Pichichero et al. Lancet 360:1737, 2002
THE BIG MISTAKE! • YET SOME INDIVIDUALS AT THE CDC AND FDA DECIDED IT WAS OK TO INJECT THIMEROSAL INTO A NEWBORN INFANT AT LEVELS THAT WOULD BE EPA SAFE IF THE INFANT WEIGHED 275 POUNDS! • The EPA “safe level” was based on mercury exposure from eating fish and whale meat. • Most of the heavy metal protection in humans is in the intestinal area as we evolved eating and drinking contaminated food and water. This is bypassed on injection of thimerosal or breathing mercury vapor.
Table 1. US Department of Education statistics on autism in children aged 6-21 served by Individuals With Disabilities Education Act (IDEA) • State 1992-1993 2001-2002 % Increase • Alabama 68 904 1,229 • Alaska 8 223 2,687 • Arizona 199 1,348 577 • Arkansas 30 774 2,480 • California 1,605 13,257 726 • Colorado 14 538 3,743 • Connecticut 164 1,470 796 • Delaware 15 294 1,860 • District of Columbia 0 144 - • Florida 582 4,328 644 • Georgia 262 2,462 840 • Hawaii 52 380 631 • Idaho 39 356 813 • Illinois 5 3,802 75,940 • Indiana 273 3,262 1,095 • Iowa 67 554 727 • Kansas 74 743 904 • Kentucky 38 1,022 2,589 • Louisiana 409 1,297 217 • Maine 37 552 1,392 • Maryland 28 2,396 8,457 • Massachusetts 493 2,681 444 • Michigan 288 4,719 1,538 • Minnesota 296 3,270 1,005 • Mississippi 0 461 • Missouri 336 1,953 481
Thimerosal is toxic to tubulin and actin. Combinations of Hg2+ and thimerosal would be at least additive.
Observation • Thimerosal, or ethyl-mercury, is a potent and rapid inhibitor of many enzymes necessary for human health. • Thimerosal or ethyl-mercury does not have to break down to Hg2+ to be toxic to these enzymes or structural proteins. • The inhibition of tubuline polymerization would disrupt neuronal connections and prevent the mitotic spindle formation needed for immune cell division. The latter would induce an immune system suppression.
Thimerosal in vaccines appeared to be more toxic than pure thimerosal! MOST VACCINES CONTAIN TRACES OF THIMEROSAL EVEN IF IT IS NOT ADDED AS A PRESERVATIVE. The vaccine thimerosal concentration was (is) 125,000 to 250,000 nanomolar!
INCREASEDNEURON DEATH DR. MARK LOVELL’S LAB
RESULT • The often used argument by pro-thimerosal advocates that the ethylmercury clears the blood to quickly to be toxic displays a lack of complete and intelligent analysis of the data. Don’t accept this argument! • Early blood mercury loss is most likely a measure of partitioning of Hg into the body and not excretion.
SYNERGISTIC EFFECTS OF HEAVY METALS IS QUITE COMPLEX AND CAN GREATLY ENHANCE THE TOXICTY OF MERCURY Shubert et al. Combined Effects in Toxicology--A Rapid systematic Testing Procedure:Cadmium, Mercury & Lead. J. of Toxicology & Environmental Health 4:763, 1978. “the administration of an essentially no response level (LD1) of a mercury salt together with a 1/20 of the LD1 of a lead salt killed all of the animals.” 2. “Generally, a combination was synergistic when the most toxic member was present at or near its LD1 dose in the presence of a much less toxic member.” Conclusion: Mixing borderline toxic levels of two toxic metals (Pb2+ & Hg2+) makes an extremely toxic solution.
SYNERGISTIC TOXICITIES Al:NEOMYCIN:TESTOSTERONE EFFECTS 50 NANOMOLAR THIMEROSAL DR. MARK LOVELL COLLABORATOR +TESTOSTERONE
Estradiol Reduces Cumulative Mercury and Associated Disturbances in the Hypothalamus-Pituitary Axis of Ovariectomized Rats. Oliveria et al. Ecotoxicol. Environ. Safety Jan.10, 2006 • Methyl-mercury induced a decrease in LHRH in the medial hypothalmus and a decrease in plasma levels of LH. These decreases in LHRH and LH were abolished by estrogenic replacement therapy. • “The estrogenic effects were associated with a reduction of mercury content of the anterior pituitary gland and medial hypothalmus, suggesting a protective estrogenic effect.”
Recent Publication On Thimerosal Exposure and Neurological Disorders: Autism Effects of Thimerosal on Nerve Growth Factor Signal Transduction and Cell Death in Neuroblastoma Cells. Parran et al., Toxicological Sciences, 2005. Data demonstrated that thimerosal could alter NGF-induced signaling at concentrations lower than those causing neuronal death. Therefore, the neurons growth and properties could be impeded at exceptionally low levels of thimerosal without killing the neurons.
Observations • The toxicity of Hg2+ and thimerosal are dramatically enhanced by other heavy metals, antibiotics and testosterone. • It appears as if infants are much more susceptible to mercury toxicity than more mature individuals. • Female hormone prevents mercury retention and damage in certain areas of the brain. Testosterone enhances thimerosal toxicity. • These findings may explain why autism spectrum disorders affect boys at a higher rate than girls.
Mercury Effects on the Immune System • The mitotic spindle is built on tubulin quite similar to that found in axons of neurons. Therefore, since the cells of the immune system must divide for an effective immune response Hg inhibits this and actively suppresses the immune system. • Thimerosal is a very potent inhibitor ofphagocytosis by mononuclear phagocytes, inhibiting the process at low 1 to 5 nanomolar levels. (Rampersad et al., Transfusion 45(3):384-93,2005). This prevents removal of microbes and ethyl-Hg damaged cells and proteins leading to greater susceptibility for microbe infection and widespread autoimmune problems.
Effects of Antibiotics, Diet and other Metals on Hg Excretion: Found in Published Literature • Rats exposed to antibiotics were severely impaired in their ability to excrete mercury. • Rats on milk versus high protein diets were much less able to excrete mercury. • The great enhancement of synergistic toxicity with Hg and other heavy metals (e.g. lead) is well documented in the literature. We have many children with other heavy metals in their bodies. • The above confounders have rarely been considered by those who write articles supporting the safety of thimerosal or dental amalgams.
MERCURY BIRTH HAIR LEVELS VS. AMALGAM FILLINGS IN AUTISTIC AND CONTROL GROUPS Hair Hg level (mcg/g) Data from A. Holmes, M. Blaxill & B. Haley, Int. J. of Toxicology v22, 2003 Controls Autistic Number of amalgams: 4-5 6-7 8-9 >10 0-3 2.64 Control: autistic ratio: 6.93 6.70 6.32 17.91 N: 22 29 30 43 15
Female Male BIRTH-HAIR MERCURY BY SEVERITY OF AUTISM Hair Hg level (ppm) Data from Amy Holmes, Mark Blaxill & Boyd Haley, Int. J. Tocicology v22, in press, 2003. Mild Mean=0.71 n=27 Moderate Mean=0.46 n=43 Severe Mean=0.21 n=24
Epidemiological Studies • A study on seven-year-old children in the Faeroe Islands found that blood pressure problems increased with decreased blood Hg. This implies retention toxicity effects of Hg in this comparison. • In the Sechylles study of >700 children, boys with higher levels of hair mercury performed better on some tests as the Boston Naming test. This implies that ability to excrete increases hair Hg levels, not exposure, in this comparison. • CONCLUSION: Blood and hair Hg levels are not a measure of exposure at low levels, but rather a measure of both exposure and ability to excrete mercury.
Observation • Mercury from dental amalgams reaches infants in utero! • Autistic infants in utero appear to have an impaired ability to excrete mercury when compared to normal children! • New concept: Low mercury levels in the hair and blood do not imply lack of toxic mercury exposure or retention in the body!
The involvement of the 2004 Institute of Medicine (IOM) report. • The 2004 IOM committee was funded by the CDC. • The 2004 IOM report cleared thimerosal as being involved in autism and recommended that no further research be done on this issue but to investigate other more fruitful areas like genetics. • The 2004 IOM report was based only on 5 epidemiological studies of questionable value. • The 2004 IOM report totally dismissed the basic science research on thimerosal toxicity and the resultant aberrant biochemistry possibly caused by mercury-like toxicity reported by several research scientists. • A recent congressionally requested NIH committee looked at the 2004 IOM report and gave it a very bad evaluation.
Who did the Epidemiological Studies the IOM depended on?? • The Verstraten studies at first showed autism rates were enhanced by thimerosal exposure. All the CDC data was lost or destroyed after it was published. Verstraten now works for a major vaccine producer in Europe. • Two studies were done by Danish (Madsen and Hviid) who worked for the Stantens Serum Institute (SSI). SSI makes thimerosal containing vaccines and sells them to other countries because they are not allowed to be used in Denmark since 1992. • One study was done in England by E. Miller. After her results were made known to the IOM the National Health Service removed thimerosal from English vaccines. • Troubling, that the opinion of the FDA is based totally on foreign, conflicted opinions. Why couldn’t the CDC find epidemiologists in the USA to do these studies??? • The Verstraten studies differed from the Danish and English study in that it did not show the dramatic protection effects of thimerosal against autism!!!!! Now also the latest Canadian study from Montreal.