MERCURY, SCIENCE AND POLITICS

1
MERCURY, SCIENCE AND POLITICS

• January 2009
• Dr. Boyd Haley
• Professor Emeritus of Chemistry/Biochemistry
• University of Kentucky

2
Visualization of Mercury Vapor Escaping from an
Aged Dental Amalgam

• From www. uninformed concent.com
• David Kennedys IAOMT tape
• IN SPITE OF THE OBVIOUS EMISSION OF Hg VAPORS
  FROM DENTAL AMALGAM THE FDA HAS STEADFASTLY
  REFUSED TO TEST THEM FOR SAFETY!

Amalgam is 50 Mercury, inches from your brain
and olfactory tissues.
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Mercury from Dental Amalgam

1. 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.
2. 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!

4
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.

5
Micrograms Hg released/24hrs/cm2 at 25oC from
amalgams kept in a sealed test tube.
DENTISTS BRAND DAY1 DAY4 DAY8 DAY11 DAY15 DAY18 DAY22 DAY25
BASCIANO Valiant 9.921 9.677 9.580 9.463 8.700 8.873 9.392 9.311
    9.751 9.262 8.886 8.202 8.074 8.014 9.563 10.322
    8.075 7.288 7.054 7.288 7.558 7.311 7.315 6.956
ECCLES Dispersalloy 9.966 9.620 10.851 10.590 11.260 9.070 9.280 9.014
    7.322 7.922 9.913 9.279 8.639 6.809 7.542 8.672
    9.206 8.685 8.599 8.480 7.783 8.270 7.936 8.997
FISCHER Valiant 5.958 5.829 4.408 4.533 4.266 4.473 5.136 4.460
    5.280 4.762 4.492 4.279 4.801 4.505 4.300 4.862
    4.596 4.704 4.929 4.867 6.147 5.798 5.936 5.468
GRUBE Valiant 6.841 6.904 6.788 5.782 8.158 7.740 7.893 8.026
    12.458 11.878 11.771 12.404 12.146 10.693 10.484 10.221
    13.911 13.421 12.618 11.176 11.669 13.439 13.208 13.090
MESSERMAN Dispersalloy 11.357 11.238 11.887 12.086 15.335 14.712 14.473 15.859
    17.796 17.484 16.765 19.584 19.321 20.716 20.696 19.995
    15.336 14.602 14.086 18.625 17.759 12.389 16.285 15.580
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From a study funded by NIH done on orphans in
Lisbon, Portugal.
GIRLS
BOYS
J. Woods, et al., Environmental Health
Perspectives (2007) 11510, 1527-1531.
7

• The previous slide shows that prolonged exposure
  to mercury vapor decreases the childs 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.

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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 HASNT 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.

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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 (as thimerosal) BOTH
  ACTIVATE A COMMON FORM OF MMP.

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BOTH Hg2 AND THIMEROSAL ACTIVATE MMP-9, AN
ENZYME THAT DIGESTS COLLAGEN AND LEADS TO TISSUE
BREAKDOWN. Other involvements of mercury
1. Hagele, et al. Mercury Activates Vascular
Endothelial Cell Phospholipase-D through Thiols
and Oxidative Stress. Inter. J. of Toxicology
(2007) 2657-69. 2.Ionescu, J. G. et al.
Increased Levels of Transition Metals in Breast
Cancer Tissue. Neuroendocrinology Letters (2006)
271, 36-39.
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Amalgams and General Health

• The constant release of mercury from dental
  amalgams would lead to the constant activation of
  the enzyme MMP (matrix metallo proteinase) that
  degrades collagen and disrupts cell to cell
  contacts.
• This would lead to rapid aging and exacerbate the
  many diseases that are associated with elevated
  MMP activity.
• Anti-aging treatments should all include the
  removal of dental amalgams, a fact based on
  science not irrelevant estimations.

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Axonal Transport - A Process Essential for the
Survival of Neurons
Dendrite
Membrane Bound Organelle
Axon
Dynien
Microtubule
Kinesin
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Only Hg2 Induces Aberrant 32P8N3GTP-ß-Tubulin
Interactions In Normal Brain Mimicking the
Observation seen in AD Brain
Normal Brain without and with Hg2.
Alzheimers Disease Brain
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EDTA Prevents Cd, Cu Zn But Not Hg Inhibition
of 32P8N3GTP Photolabeling of Brain ß-Tubulin
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Water in Which an Aged Amalgam has been Soaked
Induce Abnormal Tubulin in Normal Brain
Homogenates Mimics the Observation in
Alzheimers Diseased Brain
Placing amalgams in water makes it toxic to brain
tubulin just like adding Hg2.
Active Tubulin
Hours of Amalgam Soak
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Degenerating Neurons into Neurofibillary Tangles
by Treatment with Nanomolar Levels of Hg2.
Leong et al. NeuroReports 2001,12 (4)733-737.
MERCURY, AND ONLY MERCURY COULD CAUSE THE
FORMATION OF NFTs, THE MAJOR DIAGNOSTIC HALLMARK
OF ALZHEIMERS DISEASE!
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Immunostaining for Tubulin in Neurons treated
with Hg2. Leong et al. University of Calgary.
19
Alzheimer's Metal Concentrations in Plasma and
Cerebrospinal Fluid in Patients with Disease.
Dement Geriatr Cogn Disord. 2008 May
525(6)508-515 Epub ahead of printGerhardsson
L, Lundh T, Minthon L, Londos E. 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 lt 0.001) and AD
vasc (p lt/ 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 lt/ 0.010) and AD vasc (p lt/ 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 lt 0.001), and AD vasc (r(s)
0.68 p lt 0.001). Conclusion Besides the
raised plasma mercury concentrations, no
consistent metal pattern in plasma or CSF was
observed in patients with AD.
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Maternal amalgam dental fillings as the source of
mercury exposure in developing fetus and newborn.
Palkovicova L, Ursinyova M, Masanova V, Yu Z,
Hertz-Picciotto I. J Expo Sci Environ Epidemiol.
2007 Sep 12. Dental amalgam is a mercury-based
filling containing approximately 50 of metallic
mercury (Hg(0)). Human placenta does not
represent a real barrier to the transport of
Hg(0) hence, fetal exposure occurs as a result
of maternal exposure to Hg, with possible
subsequent neurodevelopmental disabilities in
infants. This study represents a sub-study of the
international NIH-funded project "Early Childhood
Development and polychlorinated biphenyls
Exposure in Slovakia". The main aim of this
analysis was to assess the relationship between
maternal dental amalgam fillings and exposure of
the developing fetus to Hg. The study subjects
were mother-child pairs (N99). Questionnaires
were administered after delivery, and chemical
analyses of Hg were performed in the samples of
maternal and cord blood using atomic absorption
spectrometry with amalgamation technique. The
median values of Hg concentrations were 0.63
mug/l (range 0.14-2.9 mug/l) and 0.80 mug/l
(range 0.15-2.54 mug/l) for maternal and cord
blood, respectively. None of the cord blood Hg
concentrations reached the level considered to be
hazardous for neurodevelopmental effects in
children exposed to Hg in utero (EPA reference
dose for Hg of 5.8 mug/l in cord blood). A strong
positive correlation between maternal and cord
blood Hg levels was found (rho0.79 Plt0.001).
Levels of Hg in the cord blood were significantly
associated with the number of maternal amalgam
fillings (rho0.46, Plt0.001) and with the number
of years since the last filling (rho-0.37,
Plt0.001) these associations remained significant
after adjustment for maternal age and education.
Dental amalgam fillings in girls and women of
reproductive age should be used with caution, to
avoid increased prenatal Hg exposure.
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• Mercury, and only mercury, can mimic the abnormal
  biochemistry observed in Alzheimers Diseased
  brain as detected in comparison to normal human
  brain. The vaporous form of mercury is the most
  effective as it crosses the blood-brain barrier
  with ease as shown in a study with living rats.
• Amalgams are only inches from the brain and the
  olfactory nerves and constantly release mercury
  vapor.
• Yet our FDA and ADA constantly contend that these
  vapors, shown to accumulate in the brain and
  other organs, is safe. Today the FDA is
  reevaluating the safety of dental amalgam.
  Contact them!

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Federal Register / Vol. 73, No. 82 / Monday,
April 28, 2008 / Proposed Rules

• SUMMARY The Food and Drug Administration (FDA)
  is reopening for 90 days, the comment period for
  the proposed rule, published in the Federal
  Register of February 20, 2002 (67 FR 7620), on
  the classification of
• encapsulated amalgam alloy and dental mercury,
  the reclassification of dental mercury, and the
  issuance of special controls for amalgam alloy.
• Consumers Dental Choice lawyers had to sue the
  FDA and certain officials to get them to take
  action. The lawsuit is currently underway. It
  has been over 30 years that the FDA has refused
  to evaluate and classify dental amalgams.
  Classification of amalgams is being fought by the
  American Dental Association.

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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).
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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 gt1,000ppb, and one
  was gt1,500ppb. 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.

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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 state 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 3601737, 2002

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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.

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AUTISM IN DIFFERENT AGE GROUPS IN SCOTLAND
THERE IS A LACK OF OLDER AUTISTICS!
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Thimerosal is toxic to tubulin and actin.
Combinations of Hg2 and thimerosal would be at
least additive.
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Thimerosal in vaccines appeared to be more toxic
than pure thimerosal! Most likely due to
synergistic effects of other additions like Al3.
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!
32
Hg2 THIMEROSAL DISPLAY ADDITIVE TOXICITIES TO
NEURONS IN CULTURE.
33
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 ProcedureCadmium,
  Mercury Lead. J. of Toxicology Environmental
  Health 4763, 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. 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.

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SYNERGISTIC TOXICITIES
AlNEOMYCINTESTOSTERONE EFFECTS
50 NANOMOLAR THIMEROSAL
DR. MARK LOVELL COLLABORATOR
TESTOSTERONE
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Estradiol Reduces Cumulative Mercury and
Associated Disturbances in the Hypothalamus-Pituit
ary 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.

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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 of
  phagocytosis 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.

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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.

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MERCURY BIRTH HAIR LEVELS VS. AMALGAM FILLINGS IN
AUTISTIC AND CONTROL GROUPSAUTISTICS SEEM LESS
CAPABLE OF EXCRETING MERCURY AS INFANTS.
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
gt10
0-3
Control autistic ratio
2.64
6.93
6.70
6.32
17.91
N
22
29
30
43
15
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Other 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 gt700 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.
• Healthier children seem to be more exposed to
  mercury if one believes high blood and hair Hg
  are measure of exposure.
• 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.

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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
  geneticswhich has failed to find a significant
  genetic component of autism.
• The 2004 IOM report was based only on 5
  epidemiological studies of questionable value,
  none lead by an American.
• 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 congressionally requested NIH committee looked
  at the 2004 IOM report and gave it a very bad
  evaluation.
• The CDC is living in a state of denial!

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Who did the Epidemiological Studies the IOM
depended on??

• The Verstraten (Belgium) studies at first showed
  autism rates were enhanced by thimerosal exposure
  but changed with renditions to show no effect.
  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. These studies showed a
  20-fold increase in autism on removal of
  thimerosal! STUPID!
• One study was done in England by E. Miller.
  After her results were made known at the 20004
  IOM meeting the National Health Service removed
  thimerosal from English vaccines.
• Troubling, that the opinion of the CDC is based
  totally on foreign, conflicted opinions. Why
  couldnt 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!!!!!

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Autism Risks From 5 Sequential Studies by
Verstraten et al. of CDC
Study1 Study2 Study3 Study4 Study5
7.62 (1999) 2.48
1.69 1.52 (2001)
1.00 (2005)
Indicates thimerosal is causal for autism.
Conflicts with other CDC accepted studies from
Europe!
Simpsonwood Meeting
i.e., no increased risk of autism compared to
low exposure group. Also, no evident protective
effect of thimerosal or the value would have been
much less than 1.0. Yet the Danish studies
showed that removal of thimerosal caused a 20 to
25 fold increase in autism. One of these sets of
studies has to be wrong.
After publication in 2005 all of the data for
this work was lost by the CDC!!! Go to
Safeminds.org to read the FOIA material on the
Verstraten studies.
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DANISH STUDY

1. In USA rate was 1/150 or 67/10,000!
2. Outpatients added in 1995.
3. Large Copenhagen Clinic added in1992.
4. Autism classification changed in 1994.
5. Thimerosal removed from vaccine.

Conclusion exposure to a potent neurotoxin,
thimerosal, prevents autism!!! Nonsense!
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The CDC, AAP and many pro-thimerosal proponents
quote the Danish Studies as showing that
thimerosal is not causal for autism since its
removal correlated with about a 20-fold increase
in autism. But this study is like looking at the
involvement of mosquitos with malaria and doing
the research in Alaska!

• These studies are quite unbelievable if one looks
  at the content in detail. The major question to
  the CDC and AAP is why havent the Danes, Swedes
  and English replaced thimerosal in their vaccines
  if it is proven, as these studies suggest, that
  thimerosal prevents autism?????
• Perhaps the medical establishments in these
  countries are more concerned about infant health
  than ours?

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Other Considerations

• In England, between 1970-1980, about 14.7 of
  children were not vaccinated as suggested. Yet a
  parental autism group there report (Tony
  Bateson), on the internet, only two cases of
  autism in non-vaccinated children were found in
  their search of autistics born during this time
  frame.
• The UPI series on autism by Dan Olmstead finds
• Very little, if any, autism in the unvaccinated
  Amish!
• Healthfirst, a Chicago Clinic that does not
  vaccinate in the first year of birth reports no
  autistic children born since 1985 from a
  population of about 35,000 children.
• The dramatic increase in autism in China
  following the end of the cold war and the
  importation of Western vaccines (Evidence of Harm
  by David Kirby).

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CRITICAL EXCLUSIONS

• THE CDC IGNORING OF THE EARLY REPORT BY REPORTER
  DAN OLMSTEAD OF A GREATLY DECREASED RATE OF
  AUTISM IN THE NON-VACCINATED AMISH POPULATION IS
  CRIMINAL!
• THERE IS NO RATIONAL EXPLANATION FOR THIS. THEY
  HAVE PUSHED FOR RESEARCH IN OTHER AREAS
  (GENETICS) TO AVOID FINDING THE POSSIBLE NEGATIVE
  EFFECTS OF THE CDC MANDATED VACCINE PROGRAM.
• About 25 million has recently been spent to find
  the genetic cause of autism without success!

47
THE SMOKING GUN STUDY

• Done in Paris, France (since the 2004 IOM
  committee recommended NIH not fund thimerosal
  studies) in a large autism clinic.
• Investigated porphyrin profiles in autistic
  versus normal children because these profiles are
  the best indicator for heavy metal toxicity,
  especially mercury toxicity.
• Found porphyrin profiles that indicated 53 of
  autistic children surveyed were mercury toxic.
• Reversed toxic porphyrin profiles by treating
  autistics with a mercury chelator. Therefore,
  the cause was not purely genetic, but involved
  mercury toxicity.
• Supporting data from Norway has been reported.
• Dr. Robert Natal and Dr. Richard Lathe were the
  lead researchers in this work published in the
  International J. Toxicology 2006.

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WHAT ARE PORPHYRINS?

• Porphyrins are a class of compounds that lead to
  the synthesis of heme, the iron binding red
  compound of hemoglobin that binds oxygen and aids
  in delivery to cells, where it is used in the
  mitochondria to help make energy (ATP). Lack of
  heme or hemoglobin leads to a very pale
  complexion (ever notice the complexion of
  autistic children?)
• Heme has other biological uses. It is in the
  mitochondrial electron transport system that
  makes ATP. A shortage of heme would prevent
  adequate energy production and could increase
  free radical formation.
• Heme is needed for active P450 enzymes, the
  enzymes that modify organic toxins and aid in
  removing them from the body. Heme is also needed
  to remove amyloid protein from human brain to
  prevent production of amyloid or senile plaques
  as identified with Alzheimers diseased brain.

49
OXIDATIVE STRESS The single biochemical
abnormality found in essentially all
neurological, neurodegenerative, and
neurobehavioral diseases is the increased
production of oxidative free radical compounds
and low glutathione levels. This is reflective of
oxidative stress. Oxidative stress is strongly
associated with modification of lipids,
proteins, and DNA that can lead to membrane
structural problem, enzyme inhibition and genetic
mutations.

• James SJ, Cutler P, Melnyk S, et al. Metabolic
  markers of increased oxidative stress and
  methylation capacity in children with autism. Am
  J Clin Nutr. 20048016111617.
• Ischiropoulos H, Beckman JS. Oxidative stress and
  nitration in neurodegeneration Cause, effect or
  association? J Clin Invest.
• 2003111163169.
• Muravchick S, Levy RJ. Clinical implications of
  mitochondrial dysfunction. Anesthesiology.
  2006105819837.
• Kern JK, Jones AM. Evidence of toxicity,
  oxidative stress and neuronal insult in autism. J
  Toxicol Environ Health B Crit Rev.
  20069485499.
• Larsson HJ, Eaton WW, Madsen KM, et al. Risk
  factors for autism Perinatal factors, parental
  psychiatric history and socioeconomic status. Am
  J Epidemiol. 2005101916925.
• Deth R, Muratore C, Benzercry J, et al. How
  environmental and genetic factors combine to
  cause autism A redox/methylation hypothesis.
  Neurotoxicology. 200829190201.

50
REACTIVE OXYGEN SPECIES (ROSs)

• Superoxide Anion O2 e- O2-.
• Hydrogen Peroxide O2-. HO2. (hydroperoxyl
  radical)
• 2HO2. H2O2 O2
• Hydroxyl Radical O2-. H2O2 O2 HO- HO.
  (Haber-Weiss)
• Fe2 H2O2 Fe3 HO- HO. (Fenton)
• The hydroxyl radical is the most damaging!

REMOVAL OF ROSs SOD or Superoxide Dismutase
Catalyzed Reaction. 2O2-. 2H H2O2 O2
(keeps O2-. lt10-11M) Catalyase Catalyzed
Reaction. 2H2O2 2H2O O2 Peroxidase Catalyzed
Reaction. H2O2 AH2 2H2O A A could be
reduced glutathione (GSH) Catalyase is the
enzyme that converts Hgo to Hg2!
51
Ubiquione (Co-enzyme Q) is a mitochondrial mobile
electron carrier.
Citric Acid Cycle Reducing equivalents
Both O2-. radical and the quinone radical can
leak from damaged mitochondrial membranes during
the electron transport process involved in making
ATP requiring GSH to scavenge them decreasing the
GSH/GSSG ratio.
52
Structures and General Chemistry of Glutathione
GOOD
BAD
Note the number of charges on GSH. This makes it
unlikely that it could enter any hydrophobic
location in a tissue where much of the damaging
oxidation occurs as caused by many toxicants.
53
Structures and General Chemistry of Glutathione

• Glutathione (GSH) occurs in all tissues and is
  the most abundant sulfhydryl (-SH) containing
  compound in cells. It protects many enzymes from
  inhibition by reactive oxygen species (ROS).
• 1. Enzyme-SH(active) ROS RSH
  Enzyme-S-S-R(inactive) H2O2
• 2. Enzyme-S-S-R(inactive) GSH Enzyme-SH(active
  ) G-S-S-R
• 3. Enzyme-SH(active) Hg2 Enzyme-S-Hg(inactiv
  e) H
• 4. Enzyme-S-Hg(inactive) GSH Enzyme-SH
  (active) GS-Hg
• 5. GS-Hg GSH GS-Hg-SG(excreted form) H
• GSH PROTECTS THE BODY FROM OXIDATION AND HEAVY
  METAL TOXICITY! GS-Hg-SG is probably the major
  form of mercury that is excreted from the body by
  natural means. It leaves through the bilary
  transport system of the liver into the feces, not
  through the kidney. Low GSH levels (oxidative
  stress) in effect cause increased enzyme
  inhibition by ROS and decreases the ability to
  remove many toxic metals as well as organic type
  toxins. YOU CANNOT INCREASE BODY GLUTATIONE
  LEVELS BY EATING GLUTATHIONE!

54
VIT-C GETS INTO ALL CELLS AND MITOS.
reduced
oxidized
oxidized
reduced
55
REVERSAL OF LIPID PEROXIDATION BY GLUTATHIONE
PEROXIDASE (GP) R CH3CHCH-CH(CH)n-COOH (a
poly-unsaturated fatty acid, pufa) ROOH
CH3CHCH-CH-(CH)n-COOH (an oxidized fatty acid
or O-OH a
hydroperoxide) ROOH 2GSH GSSG (oxidized
glutathione) ROH H2O The ratio of GSH
(reduced glutathione)/GSSG (oxidized glutathione)
is a measure of oxidative stress, or simply put
how much GSH is being consumed relative to how
well one can make it. The higher the GSHGSSG
ratio the better ones redox system is
functioning. It appears as if autistic children
and many other illnesses need help with their
redox system. Toxicity, and especially heavy
metal toxicity, can rapidly lower the GSHGSSG
ratio as heavy metals contribute electrons very
readily.
56
Apoptosis, cell death.

• It appears as if oxidation of GSH to GSSG
  precedes cell death in two experimental models.
• 1. Fibroblasts in culture
• 2. Regressing mammary tissue after weaning.

57
CONVERSION OF GSH TO GSSG PRECEDES CELL DEATH IN
CULTURED FIBROBASTIC CELLS
Oxidative Damage to mitochondrial DNA and GSH
oxidation in apoptosis Studies in vivo and in
vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064
58
THE REDOX RATIO OF GSSG/GSH INCREASES BEFORE
FIBROBLASTIC CELL DEATH
Oxidative Damage to mitochondrial DNA and GSH
oxidation in apoptosis Studies in vivo and in
vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064
59
GSH DROPS AND GSSG INCREASES DURING FIBROBLASTIC
CELL DEATH
Oxidative Damage to mitochondrial DNA and GSH
oxidation in apoptosis Studies in vivo and in
vitro. Esteve et al. FASEB J. 1999 V13,
1055-1064
60
GSSG AND GSH LEVELS IN REGRESSING MAMMARY GLAND
CELLS AFTER WEANING.
Oxidative Damage to mitochondrial DNA and GSH
oxidation in apoptosis Studies in vivo and in
vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064
61
CHANGE IN MITOCHONDRIAL GSSG/GSH RATIOS IN
REGRESSING MAMMARY TISSUE.
MITOCHONDRIAL GSSG IS INCREASING AND GSH IS
DECREASING WITH CELL DEATH.
Oxidative Damage to mitochondrial DNA and GSH
oxidation in apoptosis Studies in vivo and in
vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064
62
INCREASED DNA DAMAGE WITH INCREASED OXIDATIVE
STRESS IN REGRESSING MAMMARY CELLS
Oxidative Damage to mitochondrial DNA and GSH
oxidation in apoptosis Studies in vivo and in
vitro. Esteve et al. FASEB J. 1999 V13,
1055-1064
63
INCREASED H2O2 PRODUCTION IN MITOCHONDRIA FROM
APOPTIC MAMMARY GLAND.
H2O2 LEVELS
Oxidative Damage to mitochondrial DNA and GSH
oxidation in apoptosis Studies in vivo and in
vitro. Esteve et al. FASEB J. 1999 V13,
1055-1064
64
GLUTATHIONE ESTER DECREASES APOPTOSIS IN CULTURED
FIBROBASTS THEREFORE THE DEATH IS REDUCED WITH
TREATMENT THAT INCREASES INTRACELLULAR GSH
FCS fetal calf serum
NO GSH-ester
PLUS GSH-ester
Oxidative Damage to mitochondrial DNA and GSH
oxidation in apoptosis Studies in vivo and in
vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064
65
OLD CONCEPTS WE NEED TO DIRECTLY TREAT
OXIDATIVE STRESS

1. REDUCE THE PRODUCTION OF FREE RADICALS OR
   SCAVENGE THEM TO SALVAGE GSH. (REDUCING VITAMINS)
2. INCREASE PRODUCTION OF GLUTATHIONE BY PROVIDING
   PRO-GLUTATHIONE NUTRIENTS (e.g CYSTEINE) AND
   REMOVING ANY TOXICANTS (e.g. HEAVY METALS) THAT
   PREVENT SYNTHESIS.
3. PREVENT AND REVERSE THE DAMAGE CAUSED BY
   OXIDATIVE STRESS FACTORS.

66
New Antioxidant Partitioning Concept

• Most available antioxidants are water soluble
  because they carry ionic charges. DMPS, DMSA,
  glutathione, and Se2- are all charged and are
  rapidly cleared from the body. Therefore, they
  are not efficient at removing hydroxyl radicals
  that are located in fatty (hydrophobic)
  environments or inside of cells, such as the
  mitochondria.
• Therefore, most toxin generated reactive oxygen
  species (ROSs) in the body are not available to
  DMPS, etc. for binding as they are intracellular
  or in hydrophobic locations.
• The new antioxidants are needed that enter
  hydrophobic areas. Entering the hydrophobic
  regions increases the time spent in the body
  enhancing the scavenging of hydroxyl radicals.
• Therefore, the antioxidants need to be both
  effective in the ORAC test (oxygen radical
  absorbance capacity test) and hydrophobic.

67
New Hydrophobic Antioxidant Agents
Free radical scavenging sites
Potent scavengers of hydroxyl radicals in
lipophilic areas.
Benzene bis-amido bis-thiol
Pyridine bis-amido bis-thiol
Water insoluble, but lipid soluble, coupling with
glutathione makes this compound water soluble
(next slide).
68
Glutathione derivative of Antioxidant Agents
OSR compound
Note Molecule would be charged and water
soluble at pH 7.4.
Glutathione
Glutathione
Very water soluble
69
AN OXYGEN RADICAL ABSORBANCE STUDY OF ONE OF THE
NEW ANTIOXIDANTS DONE IN AQUEOUS SOLUTION.
70
Toxicity Study of Lipid Soluble Antioxidant

• Group A B C D
• Test 1 0 100 200 300
• Test 2 0 200 300 400
• Test 3 0 300 400 500
• Total 0 600 900 1,200
• Test 4 0 - 1,500 1,500
• Procedure Rats were injected under the skin in
  the stomach area with compound to the amount in
  µMoles/kg body weight. Three days pause was
  between each treatment.
• Result No toxicity or weight loss was observed
  at any level of exposure

71
TOXICITY TESTING BY ORAL DELIVERY

• A commercial toxicology laboratory has confirmed
  that the new antioxidant is not toxic at
  5grams/kg body weight when given orally, the
  highest testing level! This is equivalent to a
  100 lb person taking 227grams.
• Nor did mice given 1.0g/kg body weight for 28
  straight days demonstrate any toxic effects.
• The compounds are not mutagenic as determined by
  a FDA approved laboratory.
• This research was done for the purpose of
  submission to FDA.

72
CONCLUSIONS

• A NON-TOXIC, LIPID SOLUBLE, FREE RADICAL
  SCAVENGING ANTIOXIDANT HAS BEEN DEVELOPED AND
  FOUND TO BE WITHOUT TOXICITY IN TEST ANIMALS.
• THESE ANTIOXIDANTS SCAVENGE HYDROXYL RADICALS.
• THIS ANTIOXIDANT IS EFFECTIVE IN HELPING MAINTAIN
  A HEALTHY GLUTATHIONE LEVEL.