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86 Research Papers Supporting the Vaccine/Autism Link
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Published by Ginger Taylor
*The list has been updated and now contains 87 citations.

Media reports have claimed that there is no scientific evidence...
*The list has been updated and now contains 87 citations.

Media reports have claimed that there is no scientific evidence
supporting the link between vaccines and autism. Here we provide
for the reader research that demonstrates the link between vaccines
and autism, and the mechanisms by which vaccines can cause
autism.
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Published by: Ginger Taylor on Apr 28, 2014
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Research supporting Vaccine/Autism Causation1.
Increased risk of developmental neurologic impairment after high exposure
to thimerosal-containing vaccine in first month of life. Division of
Epidemiology and Surveillance, Vaccine Safety and Development Branch,
Immuni!ation "rogram, #enters for Disease #ontrol and
"revention. $%%%. &homas '. Verstraeten, (. Davies, D. )u, * DeStefano
Background+ #oncern has risen on the presence of the ethylmercury
containing preservative thimerosal in vaccines. assessed the risk for
neurologic and renal impairment associated past exposure to
thimerosal-containing vaccine using automated data from the Vaccine
Safety Data link VSD is a large linked data0ase from four health
maintenance organi!ations in 1regon and #alifornia, containing
immuni!ation, medical visit and demographic data on over 233,333 infants
0orn 4%$ and 4%5. 'ethods+ categori!ed the cumulative
ethylmercury exposure from &himerosalcontaining vaccines after one
month of life and assessed the su0se6uent risk of degenerative and
developmental neurologic disorders and renal disorders 0eforethe age of
six. applied proportional ha!ard models ad7usting for 8'1, year of 0irth,
and gender, excluding premature 0a0ies.(esults+ identified 9:; children
degenerative and <539 developmental neurologic disorders, and
<$3 renal disorders. &he relative risk of developing a neurologic
development disorder $.: %=> confidence intervals ?#I@ A$.$-9.:/
comparing the highest exposure group at $ month of age
9= ug/ to the unexposed group.
Within thisgroup we also found an elevated risk for the following
disorders: autism (RR #$% Cl &
, non organic sleep disorders =.3, %=> #l A $.;-$=.%C, and speech
disorders 9.$, %=> -2.3/. *or the neurologic degenerative and
renal disorders group found no significantly increased risk or a
decreased risk. #onclusion+
+his anal,sis suggests that high e-posure to eth,l mercur, from
vaccines in the first month of life increases the
risk of development of neurologic development
impairment
, 0ut not of neurologic degenerative or renal impairment. *urther
confirmatory studies are needed.

0.
8epatitis B Vaccination of 'ale and of
Epidemiology , Vol. $%, % Septem0er
933%+ ;=$-;:3, p. ;=% #' )allagher, 'S )oodman, )raduate "rogram in "u0lic
8ealth, Stony Brook 'edical #enter, Stony Brook,



immuni!ation hepatitis B
vaccine recommended in $%%$G safety findings are mixed.
&he Vaccine Safety Datalink reported no association
hepatitis B vaccination at 0irth and fe0rile episodes or neurological adverse
events. 1ther studies found positive associations hepatitis B
vaccination and ear infection, pharyngitis, and chronic arthritisG as as
receipt of early interventionHspecial education services in
pro0a0ility samples of children. #hildren autistic spectrum
disorder comprise a caseload for EIS. evaluated the
association hepatitis B vaccination of male neonates and parental
report of 'E&81DS+ &his cross-sectional study used pro0a0ility
samples o0tained from tional 8ealth Survey $%%5-9339
datasets. regression modeling used to estimate the effect of
neonatal hepatitis B vaccination on risk among0oys age <-$5
years shot records, ad7usted for race, maternal education, and
-parent household. received the hepatitis B
vaccine during the first month of life had 9.%2 greater odds for
of 5,2:;G 1( J 9.%2G p J 3.3<G %=> #I J $.$3, 5.%3/ compared to
later- or unvaccinated - 0oys ;$>less likely to
pJ3.32G %=> #IJ3.$;, 3.%2/ relative to non-
0oys.
suggest that 2.3. male neonates vaccinated with hepatitis 4
vaccine had a greater risk of A356 risk was greatest for
).
Do aluminum vaccine ad7uvants contri0ute to the rising prevalence of
autismKL Inorg Biochem. 93$$ -%%. Epu0 93$$
9<.&oml7enovic Dynamics (esearch )roup,
Department of 1phthalmology and Visual Sciences, of British
#olum0ia, :9: $3th Vancouver, B#, #anada V=J
spectrum disorders are serious
multisystem developmental disorders and an urgent glo0al pu0lic health
concern. Dysfunctional immunity and impaired 0rain function are core
deficits in the most commonly used vaccine
ad7uvant, is a demonstrated neurotoxin and a strong immune stimulator.
8ence, ad7uvant has the potential to induce neuroimmune disorders.
assessing ad7uvant toxicity in children, key points ought to 0e
considered+ children should not 0e as Msmall adultsM as their
uni6ue physiology makes them much more vulnera0le to toxic insultsG and
if exposureto from only vaccines can lead to cognitive
impairment and autoimmunity in adults, is it unreasona0le to 6uestion
the current pediatric schedules, often containing $: ad7uvanted
vaccines, are safe for childrenK By applying


8ill4s criteria for esta0lishing causality exposure and outcome
investigated exposure to from vaccines could 0e contri0uting to
the rise in prevalence in the 1ur results that+
children from countries the highest prevalence appear to have
the highest exposure to from vaccinesG the increase in exposure to
ad7uvants significantly correlates the increase in prevalence
in the States o0served over the last decades rA3.%9,
pN3.333$/G and a significant correlation exists the amounts
of administered to preschool children and the current prevalence of
in seven countries, particularly at <-2months of age
rA3.:%-3.%2, pA3.33$:-3.392:/.
+he application of the 7ill8s criteria to these data indicates that
the correlation Al in vaccines and A35 ma, causal.
Because children represent a fraction of the population most at risk for
complications exposure to a more rigorous evaluation of
ad7uvant safety seems
9.
l measles-mumps-ru0ella anti0odies and
autoimmunity in children autism.L Biomed Sci. 9339 Lul-
-;2.Singh VO, SP, E, #.,
Department of Biology and Biotechnology #enter, State
:2<99, singhvkQcc.usu.edu

to the central nervous system especially to
myelin 0asic protein may play a causal role in autism, a
neurodevelopmental disorder. Because many autistic children har0or
elevated levels of measles anti0odies, conducted a serological study of
measles-mumps-ru0ella and 'B" autoanti0odies. serum samples
of $9= autistic children and %9 control children, anti0odies assayed
0y or immuno0lotting methods. analysis a
significant increase in the level of ''( anti0odies in autistic children.
Immuno0lotting analysis revealed the presence of an unusual ''( anti0ody in
5= of $9= autistic sera 0ut not in control sera. &his anti0ody
specifically detected a protein of 5<-5= kD of ''(. &his protein 0and, as
analy!ed monoclonal anti0odies, immunopositive for measles
hemagglutinin protein 0ut not for measles nucleoprotein and ru0ella
or mumps viral proteins. &hus the ''( anti0ody in autistic sera detected
measles protein, is uni6ue to the measles su0unit of the vaccine.
*urthermore, over %3> of ''( anti0ody-positive autistic sera also
positive for 'B" autoanti0odies, suggesting a strong association ''(
and autoimmunity in autism. Stemming from this evidence,
suggest that
an inappropriate response to specificall, the measles
component thereof" might related to pathogenesis of autism.


$.
Infection, vaccines and other environmental triggers of
autoimmunity. 933= -2=.'olina V,
Shoenfeld F., Department of 'edicine B and &he #enter for
Diseases, She0a 'edical #enter, &el-8ashomer, Israel. &he
etiology of autoimmune diseases is still not clear 0ut genetic,
immunological,hormonal and environmental factors are considered to 0e
important triggers. 'ost often autoimmunity is not 0y clinical
symptoms unless an additional event such as an environmental factor favors
an overt expression. 'any environmental factors are to affect the
immune system and may play a role as triggers of the autoimmune
mosaic.Infections+ 0acterial, viral and parasitic infections are to
induce and exacer0ate autoimmune diseases, mainly 0y the mechanism of
molecular mimicry. &his studied for some syndromes as for the
association and EBV infection, pediatric autoimmune
neuropsychiatric disorders associated streptococcal infection and
more. Vaccines, in several reports found to 0e temporally 0y
onset of autoimmune diseases. &he same mechanisms that act in
infectious invasion of the host, apply e6ually to the host response to
vaccination. It has 0een accepted for diphtheria and tetanus toxoid, polio
and measles vaccines and)BS. this theory has 0een accepted for ''(
vaccination and development of autoimmune throm0ocytopenia, 'S has
0een associated 8BV vaccination. 1ccupational and other chemical
exposures are considered as triggers for autoimmunity. de0ate still exists
a0out the role of silicone implants in induction of scleroderma like
only foreign chemicals and agents have 0een associated
induction of autoimmunity, 0ut also an intrinsic hormonal exposure, such as
estrogens. &his might explain the sexual dimorphism in
autoimmunity.Better understanding of these environmental risk factors
likely lead to explanation of the mechanisms of onset and progressionof
autoimmune diseases and may lead to effective preventive involvement in
specific high-risk groups. So 0y diagnosing a patient autoimmune
disease a anamnesis should 0e done.
!.
"ositive found "revalence and
#hildhood Vaccination uptake across the "opulationLournal of
&oxicology and Environmental 8ealth, "art #urrent IssuesVolume 52,
Issue $2, 93$$, "ages %3< - %$; )ayle &he
reason for the rapid rise of autism in the States that 0egan in the
$%%3s is a mystery. individuals pro0a0ly have a genetic
predisposition to develop autism, researchers suspect that one or more
environmental triggers are also needed. 1ne of those triggers might 0e the
0attery of vaccinations that young children receive. regression
analysis and controlling for family income and ethnicity, the relationship
the proportion of children received the recommended
vaccines 0y age 9 years and the prevalence of
autism or speech or language impairment in each
state from 933$ and 9335 determined. positive and statistically
significant found+ &he higher the proportion of children
receiving recommended vaccinations, the higher the prevalence of
or $> increase in vaccination associated an
additional ;:3 children having or parental 0ehavior nor
access to care affected the results, since vaccination proportions not
significantly related to any other disa0ility or to the num0er
of pediatricians in a state.
+he results suggest that although mercur, has removed from
man, vaccines" other culprits ma, link vaccines to autism.
*urther study into the relationship vaccines and autism is
&o read the a0stract click 8E(E.

administration of a vaccine preservative, thimerosal, produces
lasting impairment of nociception and apparent activation of opioid system
in rats.Brain (es. 933% Dec :G$<3$+$2<-=$. Epu0 933% Sep %.1lc!ak ',
Dus!c!yk ', ", 'D. Department of "harmacology and
"hysiology of the System, Institute of "sychiatry
"oland. &himerosal an organomercury
preservative added to many child vaccines is a suspected factor in
pathogenesis of neurodevelopmental examined the
pharmacokinetics of 8g in the 0rain, liver and kidneys after i.m.&8I'
in7ection in suckling rats and tested &8I' effect on nociception. &8I'
solutions in7ected to and rats in a vaccination-like mode
on 5, %, $$ and $= in four e6ual doses. *or rats these
$9, 2:, 923,593, $223, 9$;3, <333 microg 8gHkg and for =2, 9$;,
=23 and $3:3 microg 8gHkg. "harmacokinetic analysis revealed that 8g
from &8I' in7ections accumulates in the rat 0rain in significant amounts and
remains there longer than<3 days after the in7ection. the ;th of age
animals examined for pain sensitivity using the hot plate test. &8I'
treated rats of 0oth strains and sexes manifested statistically significantly
elevated pain threshold for licking, 7umping/ on a hot plate
degrees #/. rats more sensitive to this effect than
rats. "rotracted &8I'-induced hypoalgesia reversed 0y naloxone
mgHkg, i.p./ in7ected 0efore the hot plate test, indicative of involvement of
endogenous opioids. &his confirmed 0y augmented catalepsy after
morphine mgHkg, s.c./ in7ection. &8I' in7ection to ;- -old
rats also produced hypoalgesia, 0ut this effect transient and gone
$2 days.
;resent findings show that administration to suckling or adult
rats impairs sensitivit, to pain" apparentl, due to activation the
endogenous opioid s,stem.'.
neuropathological changes in rat 0rain after intermittent neonatal
administration of thimerosal.
*olia -;%. 1lc!ak ', Dus!c!yk ',
", - &, 'D.Department of "harmacology and
"hysiology of the System, Institute of "sychiatry and
ul. So0ieskiego %, "oland. &himerosal, an
organomercurial added as a preservative to some vaccines, is a suspected
iatrogenic factor, possi0ly contri0uting to paediatric neurodevelopmental
disorders including autism. examined the effects of earlypostnatal
administration of thimerosal i.m. in7ections, $9 or 923 Rg &8I'-
8gHkg, on postnatal days 5, %, $$ and $=/ on 0rain pathology in rats.
neuropathological changes o0served in young adult rats
treated postnatally thimerosal. &hey included+ ischaemic
degeneration of neurons and MdarkM neurons in the prefrontal and
temporal cortex, the hippocampus and the cere0ellum, pathological changes
of the 0lood vessels in the temporal cortex, diminished synaptophysin
reaction in the hippocampus, atrophy of astroglia in the hippocampus and
cere0ellum, and positive caspase-< reaction in Bergmann astroglia.
+hese findings document neuroto-ic effects of thimerosal" at doses
to those used in infant vaccines or higher" in developing rat
suggesting likel, involvement of this mercurial in
neurodevelopmental disorders.#.
"ersistent 0ehavioral impairments and alterations of 0rain dopamine system
after early postnatal administration of thimerosal in rats.Behav Brain
(es. 93$$ Sep -$:. doi+ $3.$3$;H7.00r.93$$.32.39;. Epu0
93$$ 9:.1lc!ak ', Dus!c!yk ', ski ", 'ey!a O, 'D.
Department of "harmacology and "hysiology of the System,
Institute of "sychiatry 39-%=5 "oland.

&he neurotoxic organomercurial thimerosal used for decades as
vaccine preservative, is a suspected factor in the pathogenesis of some
neurodevelopmental disorders. "reviously that neonatal
administration of &8I' at doses e6uivalent to those used in infant vaccines or
higher, causes lasting alterations in the 0rain opioid system in rats. 8ere
investigated neonatal treatment &8I' doses $9, 923, $223 and
<333 Rg 8gHkg/ on 0ehaviors, are characteristically altered in
autism, such as locomotor activity, anxiety, social interactions, spatial
learning, and on the 0rain dopaminergic system in rats of 0oth sexes.
male and female rats, exposed to the entire range of &8I'
doses during the early postnatal life, manifested impairments of locomotor
activity and increased anxietyHneopho0ia in the open field test. In animals
of 0oth sexes treated thehighest &8I' dose, the fre6uency of prosocial
interactions reduced,
the fre6uency of asocialHantisocial interactions increased in males, 0ut
decreased in females. &8I' treatment did not significantly affect
spatiallearning and memory. &8I'-exposed rats also manifested reduced
haloperidol-induced catalepsy, accompanied 0y a marked decline in the
density of striatal D

receptors, measured 0y immunohistochemical staining, suggesting
alterations to the 0rain dopaminergic system. 'ales more sensitive than
females to someneurodisruptiveHneurotoxic actions of &8I'.
+hese data document that earl, postnatal administration causes
lasting impairmentsand neurochemical alterations in
the dependent on dose and se-. <f similar changes occur in
-posed children" the, could do
neurodevelopmental disorders.1=.
B- from a "opulation of #hildren Spectrum
Disorder and
&heir Si0lings Exhi0it 8ypersensitivity to &himerosal
L &oxicol. 93$<G93$<+:3$=$5. Epu0 93$< Lun %.Sharpe )ist
Baskin DS.Department of &he 'ethodist
Institute, 8ouston, &P. &he role of thimerosal containing vaccines
in the development of autism spectrum disorder has 0een an area
of intense de0ate, as has the presence of mercury dental amalgams and fish
ingestion 0y pregnant mothers. studied the effects of thimerosal on cell
proliferation and mitochondrial function from B-lymphocytes taken from
individuals autism, their nonautistic and their si0lings.
Eleven families examined and compared to matched controls. B-cells
increasing levels of thimerosal, and various assays
P&&, D#*8, etc./ performed to examine the effects on
cellular proliferation and mitochondrial function. su0population of eight
individuals 9 and 9 si0lings/ from four of the families
thimerosal hypersensitivity, none of the control
individuals displayed thisresponse. &he thimerosal concentration re6uired
to inhi0it cell proliferation in these individuals only 23> of controls.
#ells hypersensitive to thimerosal also had higher levels of oxidative stress
markers, protein car0onyls, and oxidantgeneration.
+his suggests certain individuals with a mild mitochondrial defect ma,
highl, to mitochondrial specific to-ins like the vaccine
preservative thimerosal.11.
Serological association of measles virus and human herpesvirus-;
0rain autoanti0odies in autism.#lin Immunol Immunopathol. $%%:
-:.Singh VO, SP, Fang V#. #ollege of "harmacy,
of 'ichigan,
'ichigan, 2:$3%-$3;=,

#onsidering an autoimmunity and autism connection, 0rain autoanti0odies
to myelin 0asic protein -'B"/ and neuron-axon filament protein -
have 0een found in autistic children. In this current study,
examined associations virus serology and autoanti0ody 0y
simultaneous analysis of measles virus anti0ody -Ig)/, human
herpesvirus-; anti0ody -;-Ig)/, anti-'B", and anti- found that
measles-Ig) and 88V-;-Ig) moderately higher in autistic children
0ut they did not significantly differ from normal controls. 'oreover,
found that a vast ma7ority of virus serology-positive autistic sera also
positive for 0rain autoanti0ody+ %3> of measles-Ig)-positive autistic
sera also positive for anti-'B"G 5<> of measles-Ig)-positive autistic
sera also positive for anti- :2> of 88V-;-Ig)-positive
autistic sera also positive for anti-'B"G and 59> of 88V-;-Ig)-
positive autistic sera also positive for anti-
+his stud, is the first to report an association virus serolog,
and in autism6 it supports the h,pothesis that a
autoimmune response ma, pla, a causal role in
autism.10.
'eta0olic 0iomarkers of increased oxidative stress and impaired methylation
capacity in children autism Lournal of #linical
Vol. :3, ;, $;$$-$;$5, Decem0er 9332Department of
"ediatrics, of for 'edical Sciences, and the
#hildren4s 8ospital (esearch Institute Background+
is a complex neurodevelopmental disorder that usually presents in early
childhood and that is thought to 0e influenced 0y genetic and environmental
factors. a0normal meta0olism of methionine and homocysteine
has 0een associated other neurologic diseases, these have
not 0een evaluated in persons autism.107ective+ &he purpose of this
study to evaluate plasma concentrations of meta0olites in the
methionine transmethylation and transsulfuration in children
diagnosed autism.Design+ "lasma concentrations of methionine, S-
adenosylmethionine S-adenosylhomocysteine adenosine,
homocysteine, cystathionine, cysteine,and oxidi!ed and reduced glutathione
measured in 93 children autism and in << control children. 1n
the 0asis of the a0normal meta0olic profile, a targeted nutritional
intervention trial folinic acid, 0etaine, and methylco0alamin
initiated in a su0set of the autistic children.(esults+ (elative to the control
children, the children autism had 0aseline plasma
concentrations of methionine, homocysteine,
cystathionine, cysteine, and total glutathione and significantly higher
concentrations of adenosine, and oxidi!ed glutathione. &his meta0olic
profile is consistent impaired capacity for methylation
ratio of to and increased oxidative stress
redox ratio of reduced glutathione to oxidi!ed
glutathione/ in children autism. &he intervention trial effective in
normali!ing the meta0olic im0alance in the autistic children.#onclusions+
An increased to o-idative stress and a decreased capacit,
for meth,lation ma, to the development and clinical
manifestation of autism
.
1).
"orphyrinuria in childhood autistic disorder+ Implications for
environmental toxicity&oxicology and "harmacology, 933;(o0ert
#orinne Skorupka0,
Spring0ettc and (ichard "hilippe "aris,
*rance, #lichy, *rance, Department of
Statistics, (oslin Institute, (oslin, "ieta (esearch, &his study
from *rance utili!es a and sophisticated measurement for
environmental toxicity 0y assessing porphyrin levels in autistic children. It
provides clear and une6uivocal evidence that children autism spectrum
disorders are more toxic than their neurotypical peers. Excerpt+
M#oproporphyrin levels elevated in children autistic disorder
relative to control groups...the elevation significant. &hese data
implicate environmental toxicity in childhood autistic
disorder.M &o address a possi0le environmental contri0ution to
autism, carried out a retrospective study on urinary porphyrin levels, a
0iomarker of environmental toxicity, in 9;% children
neurodevelopmental and related disorders referred toa "aris clinic
including $3; autistic disorder. porphyrin
levels determined 0y high-performance li6uid chromatography
compared diagnostic groups including internal and external
control groups. #oproporphyrin levels elevated in children
autistic disorder relative to control groups. Elevation maintained on
normali!ation for age or to a control heme meta0olite
in the same samples. &he elevation significant N
3.33$/. "orphyrin levels unchanged in disorder,
distinguishing it from autistic disorder. &he atypical molecule
precoproporphyrin, a specific indicator of heavy metal toxicity, also
elevated in autistic disorder N 3.33$/ 0ut not significantly in
su0group autistic disorder treated oral
dimercaptosuccinic acid a to heavy metal removal.
there a significant A 3.339/drop in urinary
porphyrin excretion.
+hese data implicate environmental to-icit, in childhood autistic
disorder.
19.
of "-mediated #alcium Signaling and Dysregulated -;
Secretion in Dendritic #ells 0y &himerosalEnvironmental
8ealth "erspectives, Luly 933;.Samuel (. )oth, (uth #hu Leffrey ".
)regg&his study demonstrates that very -levels of &himerosal can
contri0ute to immune system disregulation. Excerpt+ M1ur findings that
D#s primarily express the (y($ channel complex andthat this complex is
uncoupled 0y very levels of &8I dysregulated -; secretion raise
intriguing 6uestions a0out a molecular 0asis for immune dyregulation and
the possi0le role of the (y($ complex in genetic suscepti0ility of the immune
system to mercury.M
1$.
#omparison of Blood and Brain 'ercury in Infant 'onkeys Exposed to
'ethylmercury or Vaccines #ontaining &himerosalEnvironmental 8ealth
"erspectives, 933=.&homas Bur0acher, "hD of
study demonstrates clearly and une6uivocally that ethyl
mercury, the kind of mercury found in vaccines, not only ends up in the
0rain, 0ut leaves dou0le the amount of inorganic mercury as methyl
mercury, the kind of mercury found in fish. &his is ground0reaking
0ecause little is a0out ethyl mercury, and many health authorities
have asserted that the mercury found in vaccines is the Msafe kind.M &his
study also delivers a strong re0uke of the Institute of 'edicine4s
recommendation in 9332 to no longer pursue the mercury-autism
connection. Excerpt+ recently pu0lished I1' 9332/ appears
to have a0andoned the earlier recommendation ?of studying mercury and
autism@ as as 0ack from the of "ediatrics
goal ?of removing mercury from vaccines@. &his approach is difficult to
understand, given our current limited of the toxicokinetics and
developmental neurotoxicity of thimerosal, a compound that has 0een
continue to 0e/ in7ected in millions of and infants.M
1!.
Increases in the num0er of reactive glia in the visual cortex of 'acaca
fascicularis su0clinical long-term methyl mercury exposure.
&oxicology and "harmacology, $%%2#harleston LS, Bolender (",
'ottet Body Vahter 'E, Bur0acher &'., Department of "athology,
School of 'edicine, of &he num0er of
neurons, astrocytes, reactive glia, oligodendrocytes, endothelia, and
pericytes in the cortex of the calcarine sulcus of adult female 'acaca
fascicularis long-term su0clinical exposure to methyl mercury
and mercuric chloride inorganic mercuryG I8g/ has 0een
estimated 0y use of the optical volume fractionator stereology techni6ue.
*our groups of monkeys exposed to 'e8g micrograms 8gHkg
0ody 0y mouth for ;, $9, $:, and $9 months 0y ; months
exposure group/. fifth group of monkeys
administered I8g 8g#l9G 933 micrograms 8gHkg 0ody 0y
constant rate intravenous infusion via an catheter for < months.
(eactive glia a significant increase in num0er for every treatment
group, increasing 59> in the ;-month, $=9> in the $9-month, and $93> in
the $:-month 'e8g exposed groups, and the num0er of reactive glia in the
clearance group remained elevated &he I8g exposed group
a$;=> increase in the num0er of reactive glia. &he I8g exposed group and
the clearance group had levels of 'e8g present the tissueG
the level of I8g elevated in 0oth groups.
+hese results suggest that the <7g ma, for the increase
in reactive glia
. other cell types, including the neurons, no significant change
in num0er at the prescri0ed exposure level and durations. &he identities of
the reactive glial cells and the implications for the long-term function and
surviva0ility of the neurons due to changes in the glial population
su0clinical long-term exposure to mercury are discussed.

and in the Brain of "atients ith
of *e0 933=.Diana Vargas, 'D, Lohns
8opkins is a neurodevelopmental
disorder characteri!ed 0y impaired communication and social
interaction and may 0e accompanied 0y mental retardation and epilepsy. Its
cause remains despite evidence that genetic, environmental, and
immunological factors may play a role in its pathogenesis. &o investigate
immune-mediated mechanisms are involved in the pathogenesis of
autism, used immunocytochemistry, cytokine protein arrays, and
en!yme-linked immunosor0ent assays to study 0rain tissues and
cere0rospinal fluid from autistic patients and determined the
magnitude of neuroglial and inflammatory reactions and their cytokine
expressionprofiles. Brain tissues from cere0ellum, midfrontal, and cingulate
gyrus o0tained at autopsy from $$ patients autism used for
morphological studies. *resh-fro!en tissues availa0le from seven patients
and #S* from six living autistic patients used for cytokine protein
profiling. demonstrate an
active neuroinflammatory process in the cere0ral cortex, matter, and
nota0ly in cere0ellum of autistic patients. Immunocytochemical studies
marked activation of microglia and astroglia, and cytokine profiling
indicated that macrophage chemoattractant protein -$ and tumor
factor-0eta$, derived from neuroglia, the most prevalent
cytokines in 0rain tissues. #S* a uni6ue proinflammatory profile of
cytokines, including a marked increase in '#"-$. 1ur findings indicate that
innate neuroimmune reactions play a pathogenic role in an undefined
proportion of autistic patients, suggesting that future therapies might involve
modifying neuroglial responses in the 0rain. Excerpt+ M
4ecause this neuroinflammator, process appears to associated with
an ongoing and chronic mechanism of C>3 d,sfunction" potential
therapeutic interventions should focus on the control of its detrimental
effects and eventuall, modif, the clinical course of autism
.M
1'.
Brain Disorder, or Disorder &hat the
BrainK#linical 933='artha (. 8er0ert '.D., "h.D., 8arvard
is defined 0ehaviorally, as a syndrome of
a0normalities involving language, social reciprocity and hyperfocus or
reduced 0ehavioral flexi0ility. It is clearly heterogeneous, and it can 0e
accompanied 0y unusual talents as as 0y impairments, 0ut its
underlying 0iological and genetic 0asis in has 0een
modeled as a 0rain-0ased, strongly genetic disorder, 0ut emerging
findings and hypotheses support a 0roader model of the condition as a
genetically influenced and systemic. &hese include imaging,
neuropathology and psychological evidence of pervasive not 7ust
specific/ 0rain and phenotypic featuresG postnatal evolution and chronic
persistence of 0rain, 0ehavior and tissue changes inflammation/ and
physical illness symptomatology gastrointestinal, immune, recurrent
infection/G overlap other disordersG and reports of rate increases and
improvement or recovery that support a role for modulation of the condition
0y environmental factors exacer0ation or triggering 0y toxins,
infectious agents, or others stressors, or improvement 0y treatment/. 'odeling
autism more 0roadly encompasses previous 0ut also encourages the
expansion of research and treatment to include intermediary domains of
molecular and cellular mechanisms, as as chronic tissue, meta0olic and
somatic changes previously addressed only to a limited degree. &he
heterogeneous 0iologies underlying autism may conceiva0ly converge onto
the autism profile via multiple mechanisms on the one hand and processing
and connectivity a0normalities on the other may illuminate relevant final
common and contri0ute to focusing on the search for treatment
targets in this 0iologically and etiologically heterogeneous 0ehavioral
syndrome.
1#.
of 'ethionine Synthase 0y Insulin-like *actor-$
and Dopamine+a &arget for &oxins and
&himerosal'ol "sychiatry. 9332 - ', 1lteanu 8,
Baner7ee (, #hoi 'ason LB, "arker BS, Sukumar S, Shim S, Sharma
Ben!ecry L', -#harnitsky Deth (#. Department of "harmaceutical
Sciences, Boston, 'ethylation events
play a critical role in the a0ility of factors to promote normal
development. toxins, such as ethanol and heavy
metals, interrupt factor signaling, raising the possi0ility that they
might exert adverse effects on methylation. found that insulin-like
factor-$ -$/- and dopamine-stimulated methionine synthase
activity and folate-dependent methylation of phospholipids in S8-
SF=F human neuro0lastoma cells, via a "I<-kinase- and -kinase-
dependent mechanism. &he stimulation of this increased
methylation, its inhi0ition increased methylation-sensitive gene
expression. Ethanol potently interfered I)*-$ activation of 'S and
0locked its effect on methylation, it did not inhi0it the
effects of dopamine. 'etal ions potently affected I)*-$ and dopamine-
stimulated 'S activity, as as folate-dependent phospholipid
methylation+ promoted en!yme activity and methylation,
8 and inhi0itory. &he ethylmercury-
containing preservative thimerosal inhi0ited 0oth I)*-$- and dopamine-
stimulated methylation an of $ n' and eliminated 'S activity.
1ur findings outline a novel factor signaling that regulates
'S activity and there0y modulates methylation reactions, including
methylation.
+he potent of this pathwa, ethanol" lead" mercur,"
aluminum and thimerosal suggests that it ma, an important target
of neurodevelopmental to-ins
.
0=.
Validation of the "henomenon of (egression 8ome
Videotapes of )eneral "sychiatry, 933= Emily "hDG
)eraldine "hD, of 107ective &o
validate parental report of autistic regression using 0ehavioral data coded
from home videotapes of children autism spectrum disorder
vs typical development taken at $9 and 92 months of age. Design 8ome
videotapes of =; childrenUs first and second 0irthday parties collected
from parents of young children and a reported
history of regression and typically developing children. #hild 0ehaviors
coded 0y raters 0lind to child diagnosis and regression history.
parent that elicited information a0out parentsU recall of early
symptoms from 0irth also administered.
Setting "articipants recruited from a multidisciplinary study of autism
conducted at a ma7or university. "articipants *ifteen children
a history of regression, 9$ children early-onset autism,
and 93 typically developing children and their parents participated. 'ain
1utcome 'easures 10servations of childrenUs communicative, social,
affective, repetitive 0ehaviors, and toy play coded from videotapes of the
toddlersU first and second 0irthday parties. (esults revealed that
infants regression similar useof 7oint attention and
more fre6uent use of and 0a00le compared typical infants at $9
months of age. In contrast, infants early onset of symptoms
and no regression displayed 7oint attention and communicative
0ehaviors at $9 months of age. By 92 months of age, 0oth groupsof toddlers
displayed instances of use, vocali!ations, declarative
pointing, social ga!e, and orienting to name as compared typically
developing 92-month-olds. "arent data suggested that some
children regression displayed difficulties in regulatory 0ehavior 0efore
the regression occurred. #onclusion
+his stud, validates the e-istence of earl, autistic regression
.
01.
Blood of 'ercury (elated to Diagnosis of (eanalysis
of an Important Data SetLournal of #hild Vol. 99, $$,
$<3:-$<$$ #atherine DeSoto, "hD, (o0ert &. 8itlan, "hD -
Department of "sychology, of #edar *alls,
&he 6uestion of is leading to the apparent increase in
autism is of great importance. the link aspirin and heart
attack, even a small effect can have ma7or health implications. If there is
any link autism and mercury, it is a0solutely crucial that the first
reports of the 6uestion are not falselystating that no link occurs.
We have reanal,?ed the data set originall, reported <p et al. in 0==9
and have found that the original p value was in error and that a
significant relation does e-ist the levels of mercur, and
diagnosis of an autism spectrum disorder. the hair sample
anal,sis results offer some support for the idea that persons with
autism ma, less efficient and more at eliminating mercur,
from the
00.
Empirical Data #onfirm Symptoms (elated to
and ophen ExposureEntropy, 5, 93$9Stephanie
Seneff, (o0ert '. Davidson and Ling7ing Science and
tificial Intelligence 'assachusetts Institute of &echnology,
#am0ridge, 39$<%, Internal 'edicine )roup "ractice, Inc.,
&P 5=;32, is a condition
characteri!ed 0y impaired cognitive and social skills, associated
compromised immune function. &he incidence is alarmingly on the rise,
and environmental factors are increasingly suspected to play a role.
&hispaper investigates fre6uency patterns in the #D# Vaccine
Events (eporting System data0ase. 1ur results provide
strong evidence supporting a link autism and the aluminum in
vaccines. literature toxicity of aluminum in human
physiology offers further support. 'entions of autism in increased
steadily at the end of the last century, during a period mercury
0eing phased out, aluminum ad7uvant 0urden 0eing increased.
standard log-likelihood ratio techni6ues, identify several signs
and symptoms that are significantly more prevalent in vaccine reports after
9333, including cellulitis, sei!ure, depression, fatigue, pain and death,
are also significantly associated aluminum-containing vaccines.
We propose that children with the autism diagnosis are especiall,
vulnera to to-ic metals such as aluminum and mercur, due
toinsufficient serum sulfate and glutathione.

A strong correlation autism and the
vaccine is also which ma, partiall, e-
plained via an increased sensitivit, to acetaminophen administered to
control fever.0).
Developmental (egression and 'itochondrial Dysfunction in a #hild
L #hild 933; -9.Lon S. "oling, 'D, "hD,
Department of and 8opkins
8ospital spectrum disorders can 0e associated
mitochondrial dysfunction. present a singleton case of
developmental regression and oxidative phosphorylation disorder in a $%-
month-old girl. Su0tle a0normalities in the serum creatine kinase level,
aspartate aminotransferase, and serum 0icar0onate led us to perform a
muscle 0iopsy, type I myofi0er atrophy, increased lipid
content, and reduced cytochrome c oxidase activity. &here marked
reductions in en!ymatic activities for complex I and III. #omplex IV
c oxidase/ activity near the => confidence level. &o
determine
the fre6uency of routine la0oratory a0normalities in similar patients,
performed a retrospective study including $=% patients autism
and Statistical 'anual of 'ental Disorders-IV and #hildhood
(ating Scale/ not previously diagnosed meta0olic disorders and
%2 age-matched controls other neurologic disorders.
aminotransferase elevated in <:> of patients autism compared
$=> of controls N.333$/. &he serum creatine kinase level also
a0normally elevated in 99 of 25 patients autism. &hese data
suggest that further meta0olic evaluation is indicated in autistic patients and
that defects of oxidative phosphorylation might 0e prevalent.Excerpt+ M
Children who have d,sfunctional cellular
energ, might more prone to undergo autistic
regression 1' and )= months of age if the, also have infections
or immuni?ations at the same time

09.
1xidative Stress in Elevated #ere0ellar <-nitrotyrosine
Lournal of Biochemistry and Biotechnology 2
5<-:2, 933:Eli!a0eth '. Sa7del- - Dept of "sychiatry,
8arvard 'edical a potential link mercury and the
autopsied 0rains of young people autism. marker for oxidative stress
;:.%> higher in autistic 0rain issue than controls statistically
significant result/, mercury levels ;:.9> higher.
It has 0een suggested that oxidative stress andHor mercury compounds play
an important role in the pathophysiology of autism. &his study compared
for the first time the cere0ellar levels of the oxidative stress marker <-
nitrotyrosine - mercury and the antioxidant selenium
levels control and autistic su07ects. &issue homogenates
prepared in the presence of proteaseinhi0itors from the fro!en cere0ellar
tissue of control mean age, $=.= yearsG mean "'I, $=.= hours/ and
autistic mean age $9.$ yearsG mean "'I, $%.< hours/ su07ects.
&he concentration of cere0ellar <- determined 0y in controls
ranged from $<.;% to 2%.32 pmol g
-$
of tissueG the concentration of <- in autistic cases ranged from <.%$ to
<<<.3< pmol g
-$
of tissue. 'ean cere0ellar <- elevated in autism 0y ;:.%> and the
increase statistically significant #ere0ellar 8g, measured
0y atomic a0sorption spectrometry ranged from 3.% to <= pmol g
-$
tissue in controls and from <.9 to :3.5 pmol g
-$
tissue in autistic cases the ;:.9> increase incere0ellar 8g not
statistically significant. there a positive correlation
cere0ellar <- and 8g levels pA3.333$/. small decrease in
cere0ellar Se levels in autism, measured 0y atomic a0sorption spectroscopy,
not statistically significant 0ut accompanied 0y a 29.%> reduction
in the molar ratio of Se to 8g in the autistic cere0ellum. preliminary,
the results of the present study add elevated oxidative stress
markers in 0rain to the 0ody of data reflecting greater oxidative
stress in autism.Excerpt+
+he preliminar, data suggest a need for more e-tensive studies of o-
idative stress" its relationship to the environmental factors and its
attenuation antio-idants in autism

0$.
Brains in &he #hallenge of "ervasive
933= -23.8er0ert '(., 8arvard
#enter for 'orphometric
'assachusetts )eneral 8ospital, #harleston, &he most replicated
finding in autism neuroanatomy-a tendency to unusually large 0rains-has
seemed paradoxical in relation to the specificity of the a0normalities in three
0ehavioral domains that define autism. a range of things
a0out this phenomenon, including that 0rains in autism have a spurt
shortly after 0irth and then in a short years that
only younger 0ut not older 0rains are larger in autism than in controls, that
matter contri0utes disproportionately to this volume increase and in a
nonuniform pattern suggesting postnatal pathology, that functional
connectivity among regions of autistic 0rains is diminished, and that
neuroinflammation microgliosis and astrogliosis/ appears to 0e
presentin autistic 0rain tissue from childhood through adulthood.
these pervasive 0rain tissue and functional a0normalities, there have arisen
theories of pervasive or neural information processing or signal
coordination a0normalities as central coherence, impaired
complex processing, and underconnectivity/, are argued to underlie
the specific o0serva0le 0ehavioral features of autism. &his convergence of
findings and models suggeststhat a systems- and chronic disease-0ased
reformulation of function and pathophysiology in autism needs to 0e
considered, and it opens the possi0ility for treatment targets.. Excerpt+
M
@-idative stress" inflammation" and microgliosis have
much documented in association with to-ic e-posures including various
heav, metals...the awareness that the as well as medical
conditions of children with autism ma, conditioned chronic
such as inflammation opens the
that meaningful interventions ma, well past
the window of ma-imal neuroplasticit, in earl, childhood the
for assuming that all deficits can to fi-ed earl,
developmental alterations in neural architecture has now
undermined
.M
0!.
Evidence of &oxicity, 1xidative Stress, and Insult in L
&oxicol Environ 8ealth B #rit (ev. 933; - -%%.Oern
LO, Lones of "sychiatry, of &exas
'edical #enter at Dallas, Dallas, &exas to the
Society of autism is considered to 0e an
epidemic. &he increase in the rate of autism revealed 0y epidemiological
studies and government reports implicates the importance of external or
environmental factors that may 0e changing. &his article discusses the
evidence for the case that some children autism may 0ecome autistic
from neuronal cell death or 0rain damage sometime after 0irth as result of
insultG and addresses the hypotheses that toxicity and oxidative stress may
0e a cause of neuronal insult inautism. &he article first descri0es the
"urkin7e cell loss found in autism, "urkin7e cell physiology and
vulnera0ility, and the evidence for postnatal cell loss. Second,the article
descri0es the increased 0rain volume in autism and it may 0e related to
the "urkin7e cell loss. &hird, the evidence for toxicity and oxidative stress is
covered and the possi0le involvement of glutathione is discussed. *inally,
the article discusses may 0e happening over the course of
development and the multiple factors that may interplay and make these
children more vulnera0le to toxicity, oxidative stress, and neuronal insult.

1xidative Stress in "athophysiology. 933; -:$.
Epu0 933; Lun $9.#hauhan #hauhan Institute for Basic (esearch
in Developmental Disa0ilities, $3=3 *orest 8ill (oad, Staten Island,
is a severe developmental disorder
poorly understood etiology. 1xidative stress in autism has 0een studied
at the mem0rane level and also 0y measuring products of lipid peroxidation,
detoxifying agents as glutathione/, and antioxidants involved in the
defense system against reactive oxygen species peroxidation
markers are elevated in autism, indicating that oxidative stress is increased
in this disease. of ma7or antioxidant serum proteins, namely
transferrin iron-0inding protein/ and ceruloplasmin -0inding
protein/, are decreased in children autism. &here is a positive
correlation reduced levels of these proteins and loss of previously
ac6uired language skills in children autism. &he alterations in
ceruloplasmin and transferrin levels may lead to a0normal iron and copper
meta0olism in autism. &he mem0rane phospholipids, the prime target of
(1S, are also altered in autism. &he levels of phosphatidylethanolamine
are
decreased, and phosphatidylserine levels are increased in the
erythrocyte mem0rane of children autism as compared to their
unaffected si0lings. Several studies have suggested alterations in the
activities of antioxidant en!ymes such as superoxide dismutase, glutathione
peroxidase, and catalase in autism. altered glutathione levels
and homocysteineHmethionine meta0olism, increased inflammation,
excitotoxicity, as as mitochondrial and immune dysfunction have 0een
suggested in autism. *urthermore, environmentaland genetic factors may
increase vulnera0ility to oxidative stress in autism. &akentogether, these
studies suggest increased oxidative stress in autism that may contri0ute to
the development of this disease. mechanism linking oxidative stress
mem0rane lipid a0normalities, inflammation, a0errant immune response,
impaired energy meta0olism and excitotoxicity, leading to clinical
symptoms and pathogenesis of autism is proposed.Excerpt+ M
2pon completion of this article" participants should to: 1. 4e
aware of and clinical evidence of greater o-idative stress in
autism. 0. 2nderstand how gut" nutritional" and to-ic status in
autismare consistent with greater o-idative stress. ). how
-idant nutrients are used in the contemporar, treatment of
autism.
M
0'.
&himerosal is )lutathione Depletion+
"rotection )lutathione "recursors 933=
-:.Lames SL, Slikker <rd, 'elnyk S, E, "ogri0na ',
Lernigan S.Department of "ediatrics, of for 'edical
Sciences and #hildren4s 8ospital (esearch Institute,
(ock, &himerosol is an antiseptic containing 2%.=> ethyl
mercury that has 0een used for years as a preservative in many infant
vaccines and in flu vaccines. Environmental methyl mercury has 0een
to 0e highly neurotoxic, especially to the developing 0rain. Because
mercury has a high affinity for thiol -S8// groups, the thiol-
containing antioxidant, glutathione provides the ma7or intracellular
defense against mercury-induced neurotoxicity. #ultured neuro0lastoma
cells found to have levels of )S8 and increased sensitivity to
thimerosol toxicity compared to glio0lastoma cells that have higher 0asal
levels of intracellular )S8.
uced c,toto-icit, was associated with depletion of
intracellular in cell lines.
"retreatment $33 micro' glutathione ethyl ester or -acetylcysteine
0ut not methionine, resulted in a significant increase in
intracellular )S8 in 0oth cell types. *urther, pretreatment of the cells
glutathione ethyl ester or prevented cytotoxicity exposure to $=
micro' &himerosal. &himerosal has 0een recently removed from
most children4s vaccines, it is still present in flu vaccines given to pregnant
the elderly, and to children in developing countries. &he potential
protective effect of )S8 or against mercury toxicity further
research as possi0le ad7unct therapy to
individuals still receiving &himerosal-containing vaccinations.
0#.
ad7uvant linked to gulf illness induces motor
neuron death in mice 'ed. -$33."etrik 'S,
'#, &a0ata (#, )arry (*, of 1phthalmology and
"rogram in of British#olum0ia, Vancouver,
British #olum0ia, #anada. )ulf illness affects a
significant percentage of veterans of the $%%$ conflict, 0ut its origin
remains some cases of are increased
incidences of amyotrophic lateral sclerosis and other neurological disorders.
many environmental factors have 0een linked to the role of
the anthrax vaccine has come under increasing scrutiny. the
vaccine4s potentially toxic components are the ad7uvants aluminum
hydroxide and s6ualene. &o examine these compounds might
contri0ute to neuronal deficits associated an animal model for
examining the potential neurological impact of aluminum hydroxide,
s6ualene, or aluminum hydroxide com0ined s6ualene developed.
Foung, male colony #D-$ mice in7ected th the ad7uvants at doses
e6uivalent to those given to military service personnel. mice
su07ected to a 0attery of motor and cognitive-0ehavioral tests over a ;-mo
period postin7ections. sacrifice, central nervous system tissues
examined using immunohistochemistry for evidence of inflammation
and cell death. Behavioral testing motor deficits in the aluminum
treatment group that expressed as a progressive decrease in strength
measured 0y the -mesh hang test deficit at 92 a0out =3>/.
Significant cognitive deficits in -ma!e learning o0served in the
com0ined aluminum and s6ualene group errors per trial/ compared
the controls errors per trial/ after 93 neurons
identified in aluminum-in7ected animals that significantly
increased activated caspase-< la0eling in lum0ar spinal cord and
primary motor cortex compared the controls. -
treated groups also significant motor neuron loss and
increased num0ers of astrocytes in the lum0ar spinal cord. &he
findings suggest a possi0le rolefor the aluminum ad7uvant in some
neurological features associated and possi0ly an additional role for
the com0ination of ad7uvants.
)=.
Enrichment of Elevated "lasma *9t-Isoprostane in Individuals
Stratified 0y "resence of )astrointestinal Dysfunction
e;:222.)orrindo ", #L, EB, B, "
<, 93$</
*unding+ &his supported in part 0y Institutes of 8ealth
Institute of #hild 8ealth and 8uman Development
(9$8D3;=9:% Institute of )eneral 'edical Sciences
&<9)'35<25 for the Vander0ilt 'edical Scientist &raining "rogram
#enter for (esearch (esources : and
#enter for &ranslational Sciences for the
Vander0ilt Institute for #linical and &ranslational (esearch.
support provided 0y the 'arino (esearch Institute, the "ediatric
#linical (esearch #enter at Vander0ilt &he Scott *amily
*oundation, and the Vander0ilt &reatment Site, a
program funded 0y Speaks. is in
the ma7ority of individuals autism spectrum disorder
1ne strategy to investigate pathogenesis is to stratify this heterogeneous
disorder 0ased on a prominent phenotypic feature that enriches for
homogeneity population strata. #o-occurring gastrointestinal
dysfunction characteri!es a su0set of children 1ur current
o07ective to investigate a potential pathophysiological measure to test
the hypothesis that children 0oth and )ID have a more severe
meta0olic dysfunction than children -only, given that the highly
meta0olically active0rain and gastrointestinal system may additively
contri0ute measura0le impairment. "lasma levels of *9t-Isoprostanes -
Iso"s/, a gold standard 0iomarker of oxidative stress, measured in :5
children in four groups+ -)ID, -only, )ID-only and ed.
*9-Iso" levels elevated in all < clinical groups compared to the
group, the -)ID group significantly elevated a0ove
the -only group SD in pgHmg+ -)ID =<.;, 92.2G -
only <;.=, $<.<G p A 3.335/. for age, sex, and triglyceride levels,
*9-Iso" levels remained significantly different study groups, a
moderate effect si!e of Wp9 A 3.$:5 A 3.33$/.
Blevation in peripheral o-idative stress is consistent with" and ma,
to" the more severe functional impairments in the
group.
uni6ue medical, meta0olic, and 0ehavioral features in children
-)ID, the present findings serve as a compelling rationale for 0oth
individuali!ed approaches to clinical care and integrated studies of
0iomarker enrichment in su0groups that may 0etter address the
complex etiology of
)1.
Environmental mercury release, special education rates, and autism
disorder+ an ecological study of &exas8ealth "lace. 933; -
%."almer (*, Blanchard S, Stein J, 'andell D, 'iller of &exas
8ealth Science #enter, San Department of *amily and #ommunity
'edicine, 553< *loyd #url Drive, San &exas &he
association environmentally released mercury, special education
and autism rates in &exas investigated using data from the &exas
Education Department and the States Environmental "rotection
"oisson
regression analysis ad7usted for school district population si!e, economic
and demographic factors used. &here a significant increase in the
rates of special education students and autism rates associated
increases in environmentally released mercury. 1n average, for each $,333
l0 of environmentally released mercury, there a 2<> increase in the rate
of special education services and a ;$> increase in the rate of autism. &he
association environmentally released mercury and special
education rates fully mediated 0y increased autism rates. &his
ecological study suggests the need for further research regarding the
association environmentally released mercury and developmental
disorders such as autism. &hese results have implications for policy
planning and cost analysis.
)0.
(educed levels of mercury in first 0a0y haircuts of autistic children.Int L
&oxicol. 933< Lul- -:=.8olmes Blaxill '*, 8aley
BE. (eported rates of autism have increased sharply in the
States and the Oingdom. 1ne possi0le factor underlying these
increases is increased exposure to mercury through thimerosal-containing
vaccines, 0ut vaccine exposures need to 0e evaluated in the context of
cumulative exposures during gestation and early infancy. Differential rates
of postnatal mercury elimination may explain similar gestational and
infant exposures produce varia0le neurological effects. *irst 0a0y haircut
samples o0tained from %2 children diagnosed autism using
Diagnostic and Statistical 'anual of 'ental Disorders, 2th edition IV/
criteria and 2= age- and gender-matched controls. Information on diet,
dental amalgam fillings, vaccine history, (ho D immunoglo0ulin
administration, and autism symptom severity collected through a
maternal survey 6uestionnaire and clinical o0servation. 8air mercury levels
in the autistic group 3.25 ppm versus <.;< ppm in controls, a
significant difference. &he mothers in the autistic group had significantly
higher levels of mercury exposure through (ho D immunoglo0ulin
in7ections and amalgam fillings than control mothers. the autistic
group, hair mercury levels varied significantly across mildly, moderately,
and severely autistic children, mean group levels of 3.5%, 3.2;, and
3.9$ ppm, respectively. 8air mercury levels among controls
significantly correlated the num0er of the mothers4 amalgam fillings
and their fish consumption as as exposure to mercury through
childhood vaccines, correlations that a0sent in the autistic group. 8air
excretion patterns among autistic infants significantly reduced relative
to control. &hese data cast dou0t on the efficacy of traditional hair analysis
as a measure of total mercury exposure in a su0set of the population. In light
of the 0iological plausi0ility of mercury4s role in neurodevelopmental
disorders, the present study provides further insight into one possi0le
mechanism0y early mercury exposures could increase the risk of
autism.
)).
#ase Series of #hildren 'ercury &oxic
Encephalopathies 'anifesting #linical Symptoms of (egressive
Disorder L &oxicol Environ 8ealth 9335 'ay -
=$.)eier )eier '(.Institute of #hronic Illnesses, Inc., Silver Spring,
'aryland, Impairments in social relatedness and
communication, repetitive 0ehaviors, and stereotypic a0normal movement
patterns characteri!e autism spectrum It is clear that
genetic factors are important to the pathogenesis of
mercury exposure can induce immune, sensory, neurological,
motor, and 0ehavioral dysfunctions similar to traits defining or associated
&he Institutional Board of the Institute for #hronic
Illnesses for 8uman (esearch "rotections, Department of 8ealth
and 8uman Services, I(B num0er I(B3333=<5=/ approved the present
study. case series of nine presented to the )enetic #enters of
for a geneticHdevelopmental evaluation are discussed. Eight of
nine patients patient found to have an due to (ett4s
syndrome/ had regressive had elevated levelsof
androgensG excreted significant amounts of mercury post chelation
challengeG had 0iochemical evidence of decreased function in their
glutathione had no significant mercury exposure
except from &himerosal-containing -immune glo0ulin
preparationsG and had alternate causes for their regressive ruled
out. &here a significant dose-response relationship the
severity of the regressive o0served and the total mercury dose
children received from &himerosal-containing vaccinesH(ho -
immune glo0ulin preparations. Based upon differential diagnoses, : of %
patients examined exposed to significant mercury from &himerosal-
containing 0iologicHvaccine preparations during their fetalHinfant
developmental periods, and su0se6uently, $9 and 92 mo of age,
these previousl, normall, developing children suffered mercur, to-ic
encephalopathies that manifested with clinical s,mptoms consistent
with regressive A35s. Bvidence for mercur, into-ication should
considered in the differential diagnosis as to some
regressive A35s
.
)9.
&he #hanging "revalence of In #alifornia
Lournal of and Developmental Disorders, 933<'ark Blaxill,
study helps to refute the supposition made 0y some researchers
that autism4s epidemic may only 0e due to Mdiagnostic su0stitutionM.
Excerpt+ M
+he, have suggested that 8diagnostic accounts
for an apparent increase in the incidence of autism in California that is
not real. +his h,pothesi?ed is not supported proper and
detailed anal,ses of the California data
.M
)$.
'itochondrial Energy-Deficient Endophenotype in
Lournal of Biochemistry and Biotechnology 2 $%:-935,
933:L. Lay )argus and *ai6a Imtia!Department of "hysiology and
Biophysics and Department of "ediatrics, Section of 8uman )enetics, School
of 'edicine, of #alifornia, Irvine, Diagnostics
Oing *aisal Specialist 8ospital and (esearch #entre
evidence points to a multigenic etiology of most autism, the
pathophysiology of the disorder has yet to 0e defined and the underlying
genes and 0iochemical they su0serve remain
is considered to 0e influenced 0y a com0ination of various genetic,
environmental and immunological factorsG more recently, evidence has
suggested that increasedvulnera0ility to oxidative stress may 0e involved in
the etiology of this multifactorial disorder.*urthermore, recent studies have
pointed to a su0set of autism associated the 0iochemical
endophenotype of mitochondrial energy deficiency, identified as a su0tle
impairment in fat and car0ohydrate oxidation. &his phenotype is similar,
0ut more su0tle than those seen in classic mitochondrial defects. In some
cases the 0eginnings of the genetic underpinnings of these mitochondrial
defects are emerging, such as mild mitochondrial dysfunction and
secondary carnitine deficiency o0served in the su0set of autistic patients
an inverted duplication of chromosome $=6$$-6$<. In addition, rare
cases of familial autism associated sudden infant death syndrome
or associated a0normalities in cellular calcium homeostasis,
such as malignant hyperthermia or cardiac arrhythmia, are 0eginning to
emerge.
3uch special cases suggest that the pathoph,siolog, of autism ma,
comprise pathwa,s that are directl, or indirectl, involved in
mitochondrial energ, production
and to further pro0e this connection three avenues seem of
exploration+ $/ meta0olomic clinical studies provoking controlled aero0ic
exercise stress to expand the 0iochemical phenotype, 9/ high-throughput
expression arrays to directly survey activity of the genes underlying these
0iochemical and </ model systems, either 0ased upon neuronal
stem cells or model genetic organisms, to discover novel genetic and
environmental inputs into these
)!.
Bridging from #ells to #ognition in "athophysiology+
Biological to Defective Brain *unction and "lasticity
Lournal of Biochemistry and Biotechnology 2
$;5-$5;, 933: ". Brian S. 8ooker and 'artha (.
8er0ertDepartments of and "athology, 8arvard 'edical
SchoolHBeth Israel Deaconess 'edical #enter, 8arvard Institutes of 'edicine,
8igh &hroughput Biology &eam, *undamental Science Directorate, "acific
"ediatric for
'orphometric 'assachusetts )eneral 8ospitalH8arvard 'edical
School, and #enter for #hild and Development, #am0ridge
8ealth 'edical School evidence
to support a model the disease process underlying autism may
0egin an in utero or early postnatal environmental, infectious, sei!ure,
or autoimmune insult triggers an immune response that increases reactive
oxygen species production in the 0rain that leads to damage
and mitochondrial/ and meta0olic en!yme 0lockade and that these
inflammatory and oxidative stressors persist 0eyond early development
potential further exacer0ations/, producing ongoing functional
conse6uences. In organs a high meta0olic demand such as the central
nervous system, the continued use of mitochondria damaged
and impaired meta0olic en!yme function may generate additional (1S
cause persistent activation of the innate immune system leading
to more (1S production. Such a mechanism ould self-sustain and possi0ly
progressively &he mitochondrial dysfunction and altered redox
signal transduction found in autism conspire to activate
0oth astroglia and microglia.&hese activated cells can then initiate a 0road-
spectrum proinflammatory gene response. Beyond the direct effects of (1S
on neuronal function, receptors on neurons that 0ind the inflammatory
mediators may serve to inhi0it neuronal signaling to protect them from
excitotoxic damage during various pathologic insults infection/.
<n autism" neuroinflammator, responses could not onl,
influence neural developmental processes" ma, more significantl,
impair neural signaling involved in cognition in an ongoing fashion. +
his model makes specific predictions in patients and experimental animal
models and suggests a num0er of targets sites of intervention. 1ur model of
potentially reversi0le pathophysiological mechanisms in autism motivates
our hope that effective therapies may soon appear on the hori!on.

8eavy-'etal Emphasis on 'ercuryLohn and
Steve "iec!enik, 'D, "hD(esearch 'etals are u0i6uitous in
our environment, and exposure to them is inevita0le. not all
people accumulate toxic levels of metals or exhi0it symptoms of metal
toxicity, suggesting that genetics play a role in their potential
to damage health.
to-icit, creates multis,stem d,sfunction" which appears to
mediated primaril, through mitochondrial damage from glutathione
depletion.
screening can increase the likelihood that patients
potential metal toxicity are identified. &he most accurate screening
method for assessing chronic-metals exposure and metals load in the 0ody
is a provoked urine test.
)'.
Evidence of 'itochondrial Dysfunction in and Implications for
&reatment Lournal of Biochemistry and Biotechnology 2
93:-9$5, 933:Daniel (ossignol, L. Leffrey Bradstreet,
International #hild Development (esource #enter, #lassical
mitochondrial diseases occur in a su0set of individuals autism and are
usually caused 0y genetic anomalies or mitochondrial respiratory
deficits. in many cases of autism, there is evidence of
mitochondrial dysfunction the classic features associated
mitochondrial disease. 'tD appears to 0e more common in autism and
presents less severe signs and symptoms. It is not associated th
discerna0le mitochondrial pathology in muscle 0iopsy specimens despite
o07ective evidence of mitochondrial functioning.
B-posure to environmental to-ins is the likel, etiolog, for in autism.
+his d,sfunction then to a of diagnostic s,mptoms
and in autism including: cognitive
impairment" language deficits" energ,
chronic gastrointestinal in fatt, acid o-
idation" and increased o-idative stress. and o-idative stress ma,
also e-plain the high male to female ratio found in autism due to
increased male to these d,sfunctions.
Biomarkers for mitochondrial dysfunction have 0een identified, 0ut seem
under-utili!ed despite availa0le therapeutic interventions.
supplementation to decrease oxidative stress along factors to improve
reduced glutathione, as as hyper0aric oxygen therapy
represent supported and rationale approaches. &he underlying
pathophysiology and autistic symptoms of affected individuals 0e
expected to either improve or cease once effective treatment for
'tD is implemented.
)#.
"roximity to point sources of environmental mercury release as a predictor
of autism prevalence8ealth Y "lace, 933:(aymond *. "almer, Stephen
Blanchard, (o0ert
of &exas 8ealth Science #enter, San Department of
*amily and #ommunity 'edicine, 1ur of the San
&exas, #hair, Department of Sociology&his study should 0e
as hypothesis-generating - a first step in examining the potential role
of environmental mercury and childhood developmental disorders.
is a0out specific exposure routes, dosage, timing, and individual
suscepti0ility.
We suspect that persistent e-posures to various
environmental to-icants" including mercur," that occur during critical
windows of neural development among geneticall, children
(with a diminished capacit, for accumulated to-icants*
ma, increase the risk for developmental disorders such as autism.
Successfully identifying the specific com0ination of environmental
exposures and genetic suscepti0ilities can inform the development of
targeted prevention intervention strategies.
9=.
Epidemiology of autism spectrum disorder in "ortugal+ prevalence, clinical
characteri!ation, and medical conditionsDevelopmental 'edicine Y #hild
9335)uiomar 1liveira 'D "hD, #entro de Desenvolvimento da
#rianZa, 8ospital "edi[trico de #oim0raG \o BSc, DirecZ\o
(egional de EducaZ\o do #entro #oim0raG#arla 'ar6ues 'Sc, #entro de
Desenvolvimento da #rianZa, 8ospital "edi[tricode #oim0raG &eresa S
'iguel BSc, DirecZ\o (egional de EducaZ\o do #entro, #oim0raG
'argarida #outinho BSc, Instituto )ul0enkian de #i^ncia, 1eirasG
'ota-Vieira "hD, de )en_tica e "atologia moleculares,
8ospital do Divino Esp]rito Santo, "onta Delgada, Esmeralda
)onZalves "hDG 'endes "hD, *aculdade de #i^ncias e
&ecnologia, de #oim0raG Vitor (odrigues 'D "hDG 8enri6ue
#armona da 'ota 'D "hD, *aculdade de 'edicina, de #oim0ra,
#oim0raG 'oura Vicente "hD, Instituto )ul0enkian de #i^ncia, 1eiras,
"ortugal.`#orrespondence to first author at 8ospital "edi[trico de #oim0ra,
Bissaya Barreto, <333-35; #oim0ra, "ortugal. E-mail+
guiomarQhpc.chc.min-saude.pt &he o07ective of this study
to estimate the prevalence of autistic spectrum disorder
and identify its clinical characteri!ation, and medical
conditions in a paediatric population in "ortugal. school survey
conducted in elementary schools, targeting <<9 :3: school-aged children in
the mainland and $3 %$3 in the islands. (eferred children
directly assessed usingthe Diagnostic and Statistical 'anual of 'ental
Disorders edn/, the Diagnostic and the
#hildhood (ating Scale. #linical history and a la0oratory
investigation performed. In parallel, a systematic multi-source search
of children to have autism carried out in a restricted region.
&he glo0al prevalence of per $3 333 %.9 in mainland,
and $=.; in the intriguing regional differences.
A diversit, of associated medical conditions was documented in 0=%"
with an une-pectedl, high rate of mitochondrial respirator, chain
disorders.91.
&himerosal induces neuronal cell apoptosis 0y causing cytochrome c and
apoptosis-inducing factor release from mitochondria.International Lournal
of 'olecular 'edicine, 933;Fel Su O, )ollapudi S, )upta
S.Department of 'edicine, of #alifornia, Irvine, %9;%5,
lyelQuci.edu&here is a increasing concern over the
neurological risks of thiosalicylate/ is an
organic mercury compound that is commonly used as an antimicro0ial
preservative. In this study, that thimerosal, at nanomolar
concentrations, induces neuronal cell death through themitochondrial
&himerosal, in a concentration- and time-dependent manner,
decreased cell via0ility as assessed 0y calcein-ethidium staining and caused
apoptosis detected 0y 8oechst <<9=: dye. &himerosal-induced apoptosis
associated depolari!ation of mitochondrial mem0rane, generation
of reactive oxygen species, and release of cytochrome c and apoptosis-
inducing factor from mitochondria to cytosol.
thimerosaldid not affect cellular expression of Bax at the protein level,
o0served translocation of Bax from cytosol to mitochondria. *inally,
caspase-% and caspase-< activated in the a0sence of caspase-:
activation. 1ur data suggest that thimerosal causes apoptosis in
neuro0lastoma cells 0y changing themitochondrial microenvironment.
90.
'itochondrial mediated thimerosal-induced apoptosis in a human
neuro0lastomacell line - -S8/. 933= 8umphrey
#ole '", "endergrass L#, Oiningham OO. Department of "harmacology,
Loan #. School of 'edicine, 'arshall 8untington,
9=532-%<::, exposure to mercurials continues to 0e a
pu0lic health issue due to their deleterious effects on immune, renal and
neurological function. (ecently the safety of thimerosal, an ethyl mercury-
containing preservative used in vaccines, has 0een 6uestioned due to
exposure of infants during immuni!ation. 'ercurials have 0een reported to
cause apoptosis in cultured neuronsG the signaling
resulting in cell death have not 0een characteri!ed. &herefore, the
o07ective of this study to identify the mode of cell death in an
in vitro model of thimerosal-induced neurotoxicity, and more specifically,
to elucidate signaling might serve as pharmacological
targets. 9 h of thimerosal exposure micro'/ to the human
neuro0lastoma cell line, SO- -S8, morphological changes, including
mem0rane alterations and cell shrinkage, o0served. #ell via0ility,
assessed 0y measurement of lactate dehydrogenase activity in the
medium, as as the <-?2,=-dimethylthia!ol-9-yl@-9,=-
diphenyltetra!olium 0romide assay, a time- and
concentration-dependent decrease in cell survival upon thimerosal
exposure. In cells treated for 92 h thimerosal, fluorescence microscopy
indicated cells undergoing 0oth apoptosis and oncosisHnecrosis. &o
identify the apoptotic associated thimerosal-mediated cell
death, first evaluated the mitochondrial cascade, as 0oth inorganic and
organic mercurials have 0een reported to accumulate in the organelle.
#ytochrome c to leak from the mitochondria, 0y
caspase % cleavage : h of treatment. In addition, -ri0ose/
polymerase cleaved to forma := kDa fragment
maximal caspase < activation at 92 h. &aken together these findings
suggest deleterious effects on the cytoarchitecture 0y thimerosal and
initiation of mitochondrial-mediated apoptosis.
9).
"ossi0le Immunological Disorders in #oncomitant
and Immune &olerance &he Egyptian Lournal of Immunology, 933; 'aha I.
Sh. 1mnia (. ). 'icro0iology Department,
*aculty of 'edicine )irls/, #airo, Egypt, "sychiatry
Department, *aculty of 'edicine, #airo #airo, Egypt and
Serology Oing *ahad )eneral 8ospital, Leddah,
is a pervasive developmental disorder that affect children
early in their life. Immunological disorders is one of several contri0uting
factors that have 0een suggested to cause autism. &hirty autistic children
aged <-; years andthirty non-autistic psychologically-free si0lings
studied. #irculating and Ig) autoanti0odies to casein and gluten dietary
proteins detected 0y en!yme-immunoassays #irculating Ig)
anti0odies to measles, mumps andru0ella vaccine and cytomeglovirus
investigated 0y (esults revealed high seropositivity for
autoanti0odies to casein and gluten+ :<.<> and =3> respectively in autistic
children as compared to $3> and ;.5> positivity in the control group.
Surprisingly, circulating anti-measles, anti-mumps and anti-ru0ella Ig)
positive in only =3>, 5<.<> and =<.<> respectively as compared to $33>
positivity in the control group. -#'V Ig) positive in 2<.<> of the
autistic children as compared to 5> in the control group. It is concluded that,
autoimmune response to dietary proteins and deficient immune response to
measles, mumps and ru0ella vaccine antigens might 0e associated
autism, as a leading cause or a resulting event. *urther research is needed to
confirm these findings.
99.
"ediatric Vaccines Influence "rimate Behavior, and and
1pioid
Binding
*riday, 'ay $;, 933:+ , 10stetrics, )ynecology and
(eproductive Sciences, of "itts0urgh, "itts0urgh, B. ,
(adiology, of "itts0urgh, "itts0urgh, #. Stott , &houghtful
8ouse #enter for #hildren, &P L. &omko , "itts0urgh Development
#enter, of "itts0urgh, "itts0urgh, 8ouser , "itts0urgh
Development #enter, of "itts0urgh, "itts0urgh, E. Olein ,
Division of (esources, of "itts0urgh,
"itts0urgh, #. #astro , 10stetrics, )ynecology and (eproductive Sciences,
of "itts0urgh, "itts0urgh, ). Sackett , "sychology,
"rimate (esearch #enter, Seattle, S. )upta , 'edicine, "athology
'edicine, of #alifornia - Irvine, Irvine, D.
, #hemistry, of Oentucky, OF Blue ,
#hemistry, of Oentucky, OF E. (. , #hemistry,
of Oentucky, OF , &houghtful 8ouse
#enter for #hildren, &P Background+ 'aca6ues are
commonly used in pre-clinical vaccine safety testing,0ut the com0ined
childhood vaccine regimen, rather than individual vaccines, hasnot 0een
studied. #hildhood vaccines are a possi0le causal factor in autism, and
a0normal 0ehaviors and anomalous amygdala are potentially inter-
relatedfeatures of this condition.107ectives+ &he o07ective of this study
to compare early infant cognition and 0ehavior amygdala si!e and
opioid 0inding in rhesus maca6ues receiving the recommended childhood
vaccines -$%%%/, the ma7ority of contained the
0actericidal preservative ethylmercurithiosalicylic acid
'aca6ues administered the recommended infant
vaccines, ad7usted for age and thimerosal dose or
saline "rimate development, cognition and social
0ehavior e assessed for 0oth vaccinated and unvaccinated infants using
standardi!ed tests developed at the "rimate (esearch
#enter. and 0inding measured serially 0y '(I and 0y
the 0inding of the non-selective opioid antagonist ?$$#@diprenorphine,
measured 0y "E&, respectively, 0efore after the
administration of the measles-mumps-ru0ella vaccine (esults+
Compared with une-posed animals" significant neurodevelopmental
deficits were evident for e-posed animals in survival refle-es" tests of
color discrimination and reversal" and learning sets. 5ifferences in
were e-posed and une-posed animals
and within the e-posed group and after vaccination.
Compared with une-posed animals" e-posed animals showed
attenuation
of am,gdala growth and differences in the am,gdala of
<nteraction models identified significant
associations specific social and
isotope and vaccine e-posure.
#onclusions+
+his animal model" which e-amines for the first time"
functional" and neuromorphometric of the childhood
vaccine regimen" mimics certain neurological of
autism. +he findings raise important safet, issues
providing a potential model for examining aspects of causation and
disease pathogenesis in ac6uired disorders of 0ehavior and development.
9$.
&himerosal exposure in infants and neurodevelopmental disorders+
assessment of computeri!ed medical records in the Vaccine Safety
Datalink.Foung )eier )eier '(.&he )eorge
School of "u0lic 8ealth and 8ealth Services, Department of Epidemiology
and Biostatistics, States. &he study evaluated possi0le
associations neurodevelopmental disorders and exposure
to mercury from &himerosal-containing vaccines 0y
examining the automated Vaccine Safety Datalink total of
95:,;92 su07ects identified in 0irth cohorts from $%%3-$%%; that
had received their first oral polio vaccination 0y < months of age in the
VSD. &he 0irthcohort prevalence rate of medically diagnosed International
#lassification of Disease, %th revision -%/ specific and control
outcomes calculated. Exposures to 8g from &#Vs calculated 0y
0irth cohort for specific exposure from 0irth-5 months and 0irth-
$< months of age. "oisson regression analysis used to model the
association the prevalence of outcomes and 8g doses from &#Vs.
Consistent significantl, increased rate ratios were for
autism" autism spectrum disorders"tics" attention deficit disorder"
and emotional with 7g e-posure from +CVs.
By contrast, none of the control outcomes had significantly increased rate
ratios 8g exposure from &#Vs. (outine childhood vaccination should
0e continued to help reduce the mor0idity and mortality associated
infectious diseases, 0ut efforts should 0e undertaken to remove 8g from
vaccines. studies should 0e conducted to further evaluate the
relationship 8g exposure and
9!.
)lutathione, oxidative stress and neurodegenerationSchul! LB, L,
Seyfried L, Dichgans L.
Department of of
L Biochem. 9333 -
$$.
+here is significant evidence that the pathogenesis of several
neurodegenerative diseases" including ;arkinson8s disease"
Al?heimer8s disease" ata-ia and am,otrophic lateral
sclerosis" ma, involve the generation of reactive o-,gen species and
mitochondrial d,sfunction.
8ere, the evidence for a distur0ance of glutathione homeostasis
that may either lead to or result from oxidative stress in neurodegenerative
disorders. )lutathione is an important intracellular antioxidantthat protects
against a variety of different antioxidant species. important role for
glutathione proposed for the pathogenesis of "arkinson4s disease,
0ecause a decrease in total glutathione concentrations in the su0stantia nigra
has 0een o0served in preclinical stages, at a time at other
0iochemical changes are not yet detecta0le. Because glutathione does not
cross the 0lood-0rain 0arrier other treatment options to increase 0rain
concentrations of glutathione including glutathione analogs, mimetics or
precursors are discussed.

8epatitis B triple series vaccine and developmental disa0ility in children
aged$-% years#arolyn )allagher aG 'elody )oodman, )raduate "rogram in
"u0lic 8ealth, Stony Brook 'edical #enter, 8ealth Sciences #enter,
Fork, &oxicological Y Environmental #hemistry,
Volume %3, Issue = Septem0er 933: , pages %%5 - $33: &his
study investigated the association vaccination the 8epatitis B
triple series vaccine prior to 9333 and developmental disa0ility in children
aged years A $:92/, proxied 0y parental report that their child
receives early intervention or special education services /.
8ealth and Examination Survey data
analy!ed and ad7usted for survey design 0y &aylor using
version %.$ calla0le version %.3.$.
&he odds of receiving EIS approximately nine timesas great for
vaccinated 0oys A 2;/ as for unvaccinated 0oys A 5/, after
ad7ustment for confounders.
+his stud, found statisticall, significant evidence to suggest that in
2nited 3tates who were vaccinated with the triple series 7epatitis 4
vaccine" during the time period in which vaccines were manufactured
with thimerosal" were more to developmental
than were unvaccinated
.
9'.
Induction of metallothionein in mouse cere0ellum and cere0rum -
dose thimerosal in7ection.'inami &, 'iyata E, Sakamoto F, Fama!aki 8,
Ichida S., Department of Sciences, School of Science Y Engineering,
Oinki <-2-$ 8igashi-osaka, 1saka, =55-:=39, Lapan,
minamitaQlife.kindai.ac.7p.#ell Biology and &oxicology. 933% %.
?Epu0 ahead of print@ &himerosal, an ethyl mercury compound,
is used as a vaccine preservative. previously o0served that
the mercury concentration in mouse 0rains did not increase the clinical
dose of thimerosal in7ection, 0ut the concentration increased in the 0rain
after the in7ection of thimerosal lipopolysaccharide, even if a dose
of thimerosal administered. &himerosal may penetrate the 0rain, 0ut is
undetecta0le a clinical dose of thimerosal is in7ectedG therefore, the
induction of metallothionein messenger and protein
o0served in the cere0ellum and cere0rum of mice after thimerosal
in7ection, as '& is an induci0le protein. '&-$ expressed at ; and
% h in 0oth the cere0rum and cere0ellum, 0ut '&-$ expression in the
cere0ellum three times higher than that in the cere0rum after the
in7ection of $9 microgHkg thimerosal. '&-9 not expressed until
92 h in 0oth organs. '&-< expressed in the cere0ellum from ;
to$= h after the in7ection, 0ut not in the cere0rum until 92 h. '&-$ and '&-<
expressed in the cere0ellum in a dose-dependent manner.
*urthermore, '&-$ protein detected from ; to 59 h in the cere0ellum
after $9microgHkg of thimerosal in7ected and peaked at $3 h. '&-9
detected in the cere0ellum only at $3 h. In the cere0rum, little '&-$
protein detected at $3 and 92 h, and there no peaks of '&-9
protein in the cere0rum. In conclusion, '&-$ and '&-< 0ut not '&-9
are easily expressed in the cere0ellum rather than in the cere0rum 0y
the in7ection of -dose thimerosal. It is thought that the cere0ellum is a
sensitive organ against thimerosal.
As a result of the present findings" in with the
in patients diagnosed with autism" the
present stud, helps to support the for
how e-posure to mercur, from
vaccines ma, associated with autism.9#.
'ercury induces inflammatory mediator release from human mast
cellsDuraisamy Oempura7, Shahr!ad Bodi Jhang, 'anola,
Lennifer 8ogan, Erika "eterson, &heoharis # &heoharidesLournal of
93$3, 5+93 doi+$3.$$:;H$529-93%2-5-
93 Background+ 'ercury is n to 0e neurotoxic, 0ut its effects
on the immune system are less 'ast cells are involved in
allergic reactions, 0ut also
in innate and ac6uired immunity, as as in inflammation. 'any patients
Spectrum Disorders have
symptomsG moreover, the prevalence of in patients
mastocytosis, characteri!ed 0y numerous hyperactive mast cells in most
tissues, is $3-fold higher than the general population suggesting mast cell
involvement. therefore, investigated the effect of mercuric chloride
on human mast cell activation.'ethods+ 8uman leukemic cultured
mast cells and normal human um0ilicalcord 0loodderived cultured
mast cells stimulated 0y 8g#l9 -$3 R'/ for either $3 min
for 0eta-hexosaminidase release or 92 hr for measuring vascular endothelial
factor and -; release 0y 8g#l9 induced a
9-fold increase in -hexosaminidase release, and also significant VE)*
release at 3.$ and $ R' pgH$3; cells and pgH$3; cells,
respectively/ from mast cells compared to control cells
pgH$3; cells, nA=, pN3.3=/. of 8g#l9 R'/ to the
proinflammatory neuropeptide su0stance " 3.$ R'/ had synergestic
action in inducing VE)* from mast cells. 8g#l9 also stimulated
significant VE)* release $33 pgH$3; cells at $ R', nA=, pN3.3=/
from h#B'#s compared to control cells pgH$3; cells/, and -;
release pgH$3; cells at 3.$ R'/ compared to untreated cells
pgH$3; cells, nA=, pN3.3=/. of 8g#l9 R'/ to S"
R'/ further increased -; release. #onclusions+ 8g#l9 stimulates VE)*
and -; release from human mast cells.
+his phenomenon could disrupt the and
permit inflammation. As a result" the findings of the present
stud, provide a mechanism for how low levels of mercur,
ma, to A35pathogenesis.$=.
Influence of pediatric vaccines on amygdala and opioid ligand
0inding in rhesus maca6ue infants+ pilot study Exp
93$3, 53+ "olish Society -
Institute of Experimental Brian L.
#arol Stott2, Scott 'ason< and Laime &omko$Department of 10stetrics
and )ynecology, of "itts0urgh School of 'edicine, "itts0urgh,
&houghtful 8ouse #enter for #hildren, &P,
Department of (adiology, of "itts0urgh School of 'edicine,
"itts0urgh, 2Independent #hartered Scientist, #am0ridge,
&his longitudinal, case-control pilot study examined
amygdala in rhesus maca6ue infants receiving the complete
childhood vaccine schedule -$%%%/. structural and
functional neuroimaging undertaken to examine central effects of the
vaccine regimen on the developing 0rain. Vaccine-
exposed and saline-in7ected control infants '(I and "E& imaging
at approximately 2 and ; months of age, representing specific
timeframes the vaccination schedule. Volumetric analyses
that exposed animals did not undergo the maturational changes over time in
amygdala volumethat o0served in unexposed animals.
controlling for left amygdala volume, the 0inding of the opioid antagonist
?$$#@diprenorphine in exposed animals remained relatively
constant over time, compared unexposed animals, in a
significant decrease in 0inding occurred.
+hese results suggest that maturational changes in am,gdala volume
and the capacit, of in the am,gdala was
significantl, altered in infant receiving the vaccine schedule.
+he infant is a relevant animal model in which to investigate
specific environmental e-posures and structural/functional
neuroimaging during neurodevelopment.$1.
#ultured lymphocytes from autistic children and non-autistic si0lings up-
regulate heat shock protein in response to thimerosal
challenge. 933; -%9. Epu0 933; Lun
SL, Segal L, '.Department of "hysiology and
"harmacology, *orest School of 'edicine, -Salem,
95$=;, &here are
reports suggesting that some autistic children are una0le to mount an
ade6uate response exposure to environmental toxins. &his
potential deficit, coupled the similarity in clinical presentations of
autism and some heavy metal toxicities, has led to the suggestion that heavy
metal poisoning might play a role in the etiology of autism in uni6uely
suscepti0le individuals. &himerosal, an anti-micro0ial preservative
previously added routinely to childhood multi-dose vaccines, is composed
of 2%.;> ethyl mercury. Based on the levels of this toxin that children
receive through routine immuni!ation schedules in the first years of life, it
has 0een postulated that thimerosal may 0e a potential triggering
mechanism contri0uting to autism in suscepti0le individuals.1ne potential
risk factor in these individuals may 0e an ina0ility to ade6uately up-regulate
metallothionein 0iosynthesis in response to presentation of a heavy
metal challenge. &o investigate this hypothesis, cultured lymphocytes
from the )enetic (esource Exchange, from autistic
children and non-autistic si0lings challenged either $3 micro'
ethyl mercury, $=3 micro' !inc, or fresh media the
challenge, extracted and used to 6uery genomeM
microarrays. #ultured lymphocytes challenged !inc responded
an impressive up-regulation of '& transcripts least nine different
'&s over-expressed/
while cells challenged with thimerosal responded
regulating numerous heat shock protein transcripts" not
Although there were no apparent differences autistic and
responses in this ver, small sampling group" the
differences in e-pression profiles those cells treated with ?inc
versus thimerosalwere dramatic.
Determining cellular response, at the level of gene expression, has
important implications for the understanding and treatment of conditions
that result from exposure to neurotoxic compounds.
$0.
Sorting out the spinning of autism+ heavy metals and the 6uestion of
incidence Exp 93$3, 53+ 'ary #atherine
DeSoto` and (o0ert &. 8itlan, Department of "sychology, of
#edar *alls, reasons for the rise in autism
prevalence are a su07ect of heated professional de0ate. *eaturing a critical
appraisal of some research used to 6uestion there is a rise in cases
and if rising levels of autism are related to environmentalexposure to toxins
et al. 9335, &hompson et al. 9335, Bar0aresi et al. 933%/ aim
to evaluate the actual state of scientific In addition,
surveyed the empirical research on the topic of autism and heavy metal
toxins. 1verall, the various causes that have led to the increase in autism
diagnosis are likely multi-faceted, and understanding the causes is one of
the most important health topics today. argue that scientific research
does not support re7ecting the link the neurodevelopmental
disorder of autism and toxic exposures.
$).
"orphyrin Excretion in and #hildrenEnviron
8ealth "erspect. 93$3 -5. Epu0 93$3 Lun LS,
SE, *ulton DI, L, O, Simmonds )ranpeesheh D,
'umper E, Bradstreet LL, Echeverria D, 8eyer (ooney L"., Department
of Environmental and 1ccupational 8ealth Sciences, of
Increased urinary concentrations of
pentacar0oxyl-, precopro- and copro-porphyrins have 0een associated
prolonged mercury exposure in adults, and compara0le increases
have 0een attri0uted to 8g exposure in children autism
1BLE#&IVES+ &his study designed to measure and compare
urinary porphyrin concentrations in neurotypical children and same-
age children
autism, and to examine the association porphyrin levels and
past or current 8g exposure in children autism.'E&81DS+ &his
exploratory study enrolled 95: children 9-$9 years of age. evaluated
three groups+ pervasive developmental disorder-not
specified - and 'othersHcaregivers provided information
at enrollment regarding medical, dental, and dietary exposures.
samples fromall children ac6uired for analyses of porphyrin,
creatinine, and 8g. Differences groups for mean porphyrin and 8g
levels evaluated. regression analysis conducted to
determine porphyrin levels associated increased risk of
'ean urinary porphyrin concentrations are naturally
high in young children and decline 0y as much as 9.=-fold 9 and
$9 years of age. Elevated copro- N 3.33%/, hexacar0oxyl- N 3.3$/
and pentacar0oxyl- N 3.33$/ porphyrin concentrations
significantly associated 0ut not "DD- differences
found and in urinary 8g levels or in past 8g
exposure as determined 0y fish consumption, num0er of dental amalgam
fillings, or vaccines received.
+hese findings identif, disordered porph,rin as a salient
characteristic of autism.
8g exposures compara0le diagnostic groups, and a
porphyrin pattern consistent that seen in 8g-exposed adults not
apparent.
$9.
'itochondrial dysfunction in autism spectrum disorders+ a systematic
and meta-analysis'olecular "sychiatry advance online pu0lication 9=
Lanuary 93$$Gdoi+ $3.$3<:Hmp.93$3.$<;D (ossignol and ( E
*rye comprehensive literature search performed to
collate evidence of mitochondrial dysfunction in autism spectrum
disorders primary o07ectives. *irst, features of
mitochondrial dysfunction in the general population of children
identified. Second, characteristics of mitochondrial dysfunction in
children and concomitant mitochondrial disease
compared pu0lished literature of general populations+
ithout 'D, and non- children 'D. &he prevalence of 'D
in the generalpopulation of =.3> confidence interval <.9,
;.%>/, much higher than found in the general population &he
prevalence of a0normal 0iomarker values of mitochondrial dysfunction
high in much higher than the prevalence of 'D. Variances and
mean values of many mitochondrial 0iomarkers pyruvate,
carnitine and u0i6uinone/ significantly different and
controls. Some markers correlated severity. in
vitro and post-mortem 0rain studies consistent an elevated
prevalence of mitochondrial dysfunction in &aken together, these
findings suggest children have a spectrum of mitochondrial
dysfunction of differing severity. Eighteen pu0lications representing a total
of $$9 children and 'D identified. &he
prevalence of developmental regression sei!ures 2$>/, motor
delay gastrointestinal a0normalities female gender
and elevated lactate and pyruvate significantly higher in
compared the general population. &he prevalence
of many of these a0normalities s similar to the general population
of children 'D, suggesting that represents adistinct su0group
of children 'D. 'ost cases not associated
genetic a0normalities, raising the possi0ility of secondary mitochondrial
dysfunction. &reatment studies for limited, although
improvements noted in some studies carnitine, co-en!yme
and B-vitamins. 'any studies suffered from limitations, including small
sample si!es, referral or pu0lication 0iases, and varia0ility in protocols for
selecting children for 'D collecting mitochondrial 0iomarkers and
defining 'D.
@verall" this evidence supports the notion that mitochondrial
d,sfunction is associated with A35.
studies are needed to further define the role of mitochondrial
dysfunction in
$$.
Sensiti!ation effect of thimerosal is mediated in vitro via reactive oxygen
species and calcium signaling.&oxicology. 93$3 Luly - -
</+$-%. Epu0 93$3 'ay $3.'igdal #, *oggia &ailhardat ', #ourtellemont ",
8aftek ', Serres '.&himerosal, a mercury derivative composed of ethyl
mercury chloride and thiosalicylic acid is used as
a preservative in vaccines and cosmetic products and causes cutaneous
reactions. Since dendritic cells play an essential role in the immune
response, the sensiti!ation potency of chemicals studied in vitro using
a human promyelomonocytic cell line that is used as a surrogate of
monocytic differentiation and activation. #urrently, this cell line is under
#enter for the Validation of 'ethods/
validation as an alternative method for discriminating chemicals.
&himerosal and mercury derivatives induced in an overexpression
of #D:;and interleukin -: secretion similarly to $-chloro-9,2-
dinitro0en!ene asensiti!er used as a positive control for D#
activation. -sensiti!ers, dichloronitro0en!ene and
sodium dodecyl sulfate an irritant,had no effect. activation
prevented 0y cell pretreatment -acetyl-l-cysteine 0ut
not thiol-independent antioxidants except vitamin E affected
#D:; expression 0y preventing lipid peroxidation of cell mem0ranes.
&himerosal, Et8g#l and induced glutathione depletionand
reactive oxygen species $=minG another peak detected
after 9h for mercury compounds only. 'itoS1P, a specific mitochondrial
fluorescent pro0e, confirmed that (1S essentially produced 0y
mitochondria in correlation its mem0rane depolari!ation. #hanges in
mitochondrial mem0rane permea0ility induced 0y mercury reversed
0y
0ut not 0y thiol-independent antioxidants. &himerosal and Et8g#l
also induced a calcium influx a peak at <h, suggesting that
influxis a secondary event (1S induction as
influx suppressed after pretreatment 0ut not thiol-
independent antioxidants. influx also suppressed culture
medium deprived of confirming the specificity of the measure.
<n conclusion" these data suggest that thimerosal induced
activation via o-idative stress from mitochondrial stores and
mitochondrial depolari?ation with a primordial effect of
thiol groups.
cross-talk (1S and influx demonstrated.
$!.
going onK &he 6uestion of time trends in autism."u0lic 8ealth (ep.
9332 - -=$.Blaxill '*. Increases in the
reported prevalence of autism and autistic spectrum disorders inrecent years
have fueled concern over possi0le environmental causes. &he author
the availa0le survey literature and finds evidence of large increases
in prevalence in 0oth the States and the Oingdom that cannot
0e explained 0y changes in diagnostic criteria or improvements in case
ascertainment. Incomplete ascertainment of autism cases in young child
populations is the largest source of predicta0le 0ias in prevalence surveysG
this 0ias has, if anything, against the detection of an
trend in recent surveys. #omparison of autism rates 0y year of 0irth
for specific geographies provides the strongest 0asis for trend assessment.
Such comparisons large recent increases in rates of autism and
autistic spectrum disorders in 0oth the and the (eported rates of
autism in the States increased from N < per $3,333 children in the
$%53s to <3 per $3,333 children in the $%%3s, a $3-fold increase. In the
Oingdom, autism rates rose from N $3 per $3,333 in the $%:3s to
roughly <3 per $3,333 in the $%%3s. (eported rates for the full spectrum of
autistic disorders rose from the = to$3 per $3,333 range to the =3 to :3 per
$3,333 range in the countries. precautionary approach suggests that
the rising incidence of autism should 0e a matter of urgent pu0lic concern.

Vaccines and septem0er num0er
volume <<Bernard (imland, "hD, 'c)innis, 'D
(esearch Institute, San Diego,
Excerpt+ M
Vaccinations ma, one of the triggers for autism. data
demonstrate immune in man, autistic children consistent
with impaired resistance to infection" activation of inflammator,
response" and autoimmunit,. <mpaired resistance ma, predispose to
vaccine inEur, in autism
.M
$'.
&heoretical aspects of autism+ Lournal of
Immunotoxicology, Lanuary-'arch 93$$, Vol. :, $ , "ages ;:-5%8elen V.
(ata7c!ak, "hD a mem0er of the pervasive developmental
disorders has 0een increasing dramatically since its description
0y Oanner in $%2<. *irst estimated to occur in 2 to = per $3,333
children, the incidence of autism is $ per $$3 in the States, and
$ per ;2 in the Oingdom, similar incidences throughout the
Searching information from $%2< to the present in "u0'ed and 1vid
'edline data0ases, this summari!es results that correlate the timing of
changes in incidence environmental changes. could result
from more than one cause, different manifestations in different
individuals that share common symptoms. Documented causes of autism
includegenetic mutations andHor deletions, viral infections, and
encephalitis vaccination.
+herefore" autism is the result of genetic defects and/or inflammation
of the +he inflammation could caused a
defectiveplacenta" immature the immune
response of the mother to infection while pregnant" a premature
encephalitis in the child after or a to-ic environment.$#.
of pink disease acrodynia/ identified as a risk
factor for autism spectrum disorders.L &oxicol Environ 8ealth 93$$
Sep -%2.Shandley O,
Bio-(esearch Initiative Brain and "sychological Sciences (esearch
#entre , of &echnology , , Victoria ,
"ink disease acrodynia/ especially
prevalent in the first half of the 93th century. "rimarily attri0uted to
exposure to mercury commonly found inteething the
condition developed 0y approximately $ in =33 exposed children. &he
differential risk factor identified as an idiosyncratic sensitivity to 8g.
disorders have also 0een postulated to 0e
produced 0y 8g. to the pink disease experience, 8g exposure is
yet only a fraction of exposed children develop an
suggesting sensitivity to 8g may also 0e present in children an
&he o07ective of this study to test the hypothesis that individuals
a hypersensitivity to 8g disease survivors/ may 0e more
likely to have descendants an *ive hundred and -
participants had previously 0een diagnosed pink disease
completed a survey on the health outcomes of their descendants. &he
prevalence rates of and a variety of other clinical conditions
diagnosed in childhood deficit hyperactivity disorder, epilepsy,
*ragile P syndrome, and syndrome/ ere compared to -
esta0lished general population prevalence rates. &he results the
prevalence rate of among the grandchildren of pink disease survivors
in 99/ to 0e significantly higher than the compara0le general population
prevalence rate in $;3/.
+he results support the h,pothesis that 7g sensitivit, ma, a
risk factor for A35.!=.
(isk *actors for (egression+ (esults of an #ohort
Study.L #hild rol. 93$9 Lan <3. ?Epu0 ahead of print@Jhang F, Pu
L, S#, Pu P., Department of #hild 8ealth #are, #hildren4s 8ospital of
*udan #hina. su0group of children
diagnosed autism experience developmental regression featured
0y a loss of previously ac6uired a0ilities. &he pathogeny of autistic
regression is although many risk factors likely exist. &o 0etter
characteri!e autistic regression and investigate the association
autistic regression and potential influencing factors in #hinese autistic
children, conducted an am0ispective study a cohort of $53 autistic
su07ects. 0y multiple logistic regression significant
correlations autistic regression and fe0rile sei!ures A <.=<,
%=> #I A $.$5-$3.;=, " A .39=/, as as a family history of
neuropsychiatric disorders A <.;9, %=> #I A $.<=-%.5$, " A .3$$/.
+his stud, suggests that sei?ures and famil, histor, of
neurops,chiatric disorders are correlated with autistic regression.!1.
events $9 and $: month vaccinations+ a
population-0ased,
self-controlled case series analysis
. 1ne. Epu0 93$$ Dec O, S,
L#, Deeks S, Van #, "otter BO,
#hakra0orty ", Oeelan L, "luscauskas ', 'anuel D. Department of 'edicine,
8ospital (esearch Institute, of #anada.

vaccines have distinct safety profiles,
potentially causing systemic reactions one to 9 after administration.
In the province of 1ntario, #anada, live ''( vaccine is currently recommended
at age $9 months and $: the self-controlled case
series design examined 95$,2%= $9 month vaccinations and $:2,<$9 $:
month vaccinations to examine the relative incidence of the composite
endpoint of emergency room visits or hospital admissions in consecutive
one day intervals ng vaccination. &hese compared to a control
period 93 to 9: days later. In a post-hoc analysis examined the reasons
for emergency room visits and the average acuity score atpresentation for
children during the at-risk period the $9 month
vaccine. *our to $9 days post $9 month vaccination, children
had a $.<< -$.<:/ increased relative incidence of the com0ined
endpoint compared to the control period, or at least one event during the
risk interval for every $;: children vaccinated. &en to $9 days post $: month
vaccination, the relative incidence $.$5-$.<</
represented at least one excess event for every 5<3children vaccinated. &he
primary reason for increased events statistically significant elevations
in emergency room visits all vaccinations. &here non-
significant increases in hospital admissions.
+here were an additional0= sei?ures for ever, 1=="===
vaccinated at 10 months.
are significantly elevated risks of primarily
emergency room visits approximately one to $9 and
$: month vaccination. *uture studies should examine these events
could 0e predicted or prevented.
!0.
tion of thimerosal to infant rats increases of
glutamate and aspartate in the prefrontal cortex+ protective role of
dehydroepiandrosterone sulfate. (es. 93$9 -
25. Epu0 93$$ 1ct 9$.Dus!c!yk-Budhathoki ', 1lc!ak ', ',
'D. 'arie #urie #hairs "rogram, Department of "harmacology and "hysiology
of System, Institute of "sychiatry and 39-%=5,
"oland. &himerosal, a mercury-containing vaccine
preservative, is a suspected factor in the etiology of neurodevelopmental
disorders. previously that its administration to infant rats causes
0ehavioral, neurochemical and neuropathological a0normalities similar to
those present in autism. 8ere
examined, using microdialysis, the effect of thimerosal on extracellular
levels of neuroactive amino acids in the rat prefrontal cortex
&himerosal administration in7ections, i.m., 923 Rg 8gHkg on postnatal
days 5, %, $$, $=/ induced lasting changes in amino acid an
increase of glutamate and aspartate accompanied 0y a decrease of glycine
and alanineG measured $3-$2 after the in7ections. *our in7ections of
thimerosal at a dose of $9.= Rg 8gHkg did not alter glutamate and aspartate
concentrations at microdialysis time 0ased on thimerosal
pharmacokinetics, could have 0een effective soon after its in7ection/.
of thimerosal to the "*# in perfusion fluid evoked a rapid
increase of glutamate #oadministration of the neurosteroid,
dehydroepiandrosterone sulfate :3 mgHkgG i.p./ prevented the
thimerosal effect on glutamate and aspartateG the steroid alone had no
influence on these amino acids. #oapplication of thimerosal in
perfusion fluid also 0locked the acute action of thimerosal on glutamate. In
contrast, alone reduced of glycine and alanine,
potentiating the thimerosal effect on these amino acids.
3ince e-cessive accumulation of e-tracellular glutamate is linked with e-
citoto-icit," our data impl, that neonatal e-posure to
vaccines might induce e-citoto-ic
inEuries" leading to neurodevelopmental disorders.
partially protect against mercurials-induced neurotoxicity.
!).
of &himerosal #auses "ersistent #hanges in 'u
1pioid (eceptors in the (at Brain (es. 93$3
1lc!ak, 'ichalina Dus!c!yk,
&eresa and 'aria Dorota Department of
"harmacology and "hysiology of the System, Institute of
"sychiatry and So0ieskiego % str., 39-%=5 "oland,
Department of *orensic 'edicine, 'edical of 1c!ki $ str.,
39-335 "oland, Department of Institute of
"sychiatry and 39-%=5 "oland, Department of
Biology and Environmental Science, of #ardinal Stefan
Str. $H<, 3$-:$=
"oland &himerosal added to some pediatric vaccines is suspected
in pathogenesis of several neurodevelopmental disorders. 1ur previous
study that thimerosal administered to suckling rats causes
persistent, endogenous opioid-mediated hypoalgesia. 8ere examined,
using immunohistochemical staining techni6ue, the density of R-opioid
receptors in the 0rains of rats, inthe second postnatal
received four i.m. in7ections of thimerosal at doses $9,923, $,223 or <,333
Rg 8gHkg. &he peria6ueductal gray, caudate putamen and hippocampus
examined. &himerosal administration caused dose-dependent
statistically significant increase in '1( densities in the peria6ueductal gray
and caudate putamen, 0ut decrease in the dentate gyrus, it
accompanied 0y the presence of degenerating neurons and loss of synaptic
vesicle marker
+hese data document that e-posure
to thimerosal during earl, postnatal life produces lasting alterations in
the densities of opioid receptors along with other
neuropathological changes" which ma,
development.!9.
of #ompensated #ases of Vaccine-
Induced Brain In7ury"ace Environmental vol. 9:, no. 9,
93$$'ary 8olland, #onte, (o0ert and #olinExecutive
SummaryIn $%:;, #ongress created the Vaccine In7ury #ompensation
"rogram under the #hildhood Vaccine In7ury
&his "rogram has original 7urisdiction for childrenUs claims of
vaccine in7ury. Because almost all children receive multiple vaccinations
for daycare and school, it is critically important that the "rogram provides
fundamental fairness, due process and transparency.
+his empirical investigation" in a law
Eournal" e-amines claims that the V<C; compensated for
encephalopath, and sei?ure disorder. +he V<C; has
compensated appro-imatel, 0"$== claims of vaccine inEur, since the
inception of the program. +his stud, found ') cases of acknowledged
rain damage that include autism" a disorder that
affects speech" social communication and
In 9$ pu0lished cases of the #ourt of *ederal #laims, administers the
VI#", the #ourt stated that the petitioners had autism or descri0ed autism
unam0iguously. In ;9 remaining cases, the authors identified settlement
agreements 8ealth and 8uman Services compensated children
vaccine-induced 0rain damage, also have autismor an autism
spectrum disorder."arents reported the existence of autism in telephone
and supplied supplemental materials including medical
diagnoses, school records, and completed, standard autism screening
6uestionnaires to verify their reports. In <%of the :< cases, or 25> of the
cases of vaccine in7ury r there is confirmation of autism or autism
spectrum disorder 0eyond parental report.
+his finding of autism in compensated cases of vaccine inEur, is
significant. 2.3. government spokespeople have asserting no
link for more than a decade. +his finding calls into
decisions of the Court of Claims in the
Autism ;roceeding in 0==# and 0=1= and the statement of 7ealth and
7uman 3ervices on its that F773 has never concluded in an,
case that autism was caused vaccination.G
pu0licly availa0le information, the investigation that the VI#"
has 0een compensating cases of vaccine-induced 0rain damage associated

autism for more than years. &his investigation suggests that officials
at 88S, the Department of Lustice and the #ourt of *ederal #laims may have
0een of this association 0ut failed to pu0licly disclose it.&he study
calls on #ongress to thoroughly investigate the VI#", including a medical
investigation of compensated claims of vaccine in7ury. &his investigation
calls on #ongress to get to these critically important
6uestions.
!$.
Integrating experimental vitro and in vivo/ neurotoxicity studies of
-dose thimerosal relevant to vaccines. (es. 93$$
-<:. doi+ $3.$335Hs$$3;2-3$$-3295-3. Epu0 93$$ *e0
9=. L), *aculty of 8ealth Sciences, de Bras]lia, #"
32<99, 53%$%-%53, Bras]lia, D*, Bra!il. doreaQrudah.com.0r

&here is a need to interpret neurotoxic studies to help deal
uncertainties surrounding pregnant mothers, and young children
must receive repeated doses of &himerosal-containing vaccines
&his integratesinformation derived from emerging
experimental studies vitro and in vivo/ of -dose &himerosal
ethyl mercury thiosalicylate/. 'a7or data0ases and -
of-science/ searched for in vitro and in vivo experimental studies that
addressed the effects of -dose &himerosal ethylmercury/ on neural
tissues and animal 0ehaviour. Information extracted fromstudies indicates
that+ activity of doses of &himerosal against isolated human and
animal 0rain cells found in all studies and is consistent 8g
neurotoxicityG the neurotoxic effect of ethylmercury has not 0een
studied co-occurring ad7uvant- in &#VsG animal studies have
that exposure to &himerosal-8g can lead to accumulation of
inorganic 8g in 0rain, and that doses relevant to &#V exposure possess
the potential to affect human neuro-development. &himerosal at
concentrations relevant for infants4 exposure vaccines/ is toxic to
cultured human-0rain cells and to la0oratory animals. &he persisting use of
&#V developing countries/ is counterintuitive to glo0al effortsto
8g exposure and to 0an 8g in medical productsG its continued use in &#V
re6uires evaluation of a sufficiently nontoxic level of ethylmercury
compati0le repeated exposure -occurring ad7uvant-
during early life.
!!.
8epatitis B vaccine induces apoptotic death in 8epa$-; cells
93$9 Lan $5. 8am!a 8, #ao L, P, #, Jhu ', Jhao S.
Oey of )enetics, Breeding, and (eproduction of
'inistry of Education, #ollege of Science and &echnology,
8ua!hong 2<3353, "eople4s (epu0lic of
#hina, Vaccines can have adverse
side-effects, and these are predominantly the inclusion of
chemical additives such as aluminum hydroxide ad7uvant. &he o07ective
of this study to esta0lish an in vitro model system amena0le
tomechanistic investigations of cytotoxicity induced 0y hepatitis B vaccine,
and to investigate the mechanisms of vaccine-induced cell death. &he
mouse liver hepatoma cell line 8epa$-; treated doses of
ad7uvanted iniumhydroxide/ hepatitis B vaccine and $ Rg
protein per ml/ and cell integrity after 92, 2: and 59 h.
8epatitis B vaccine exposure increased cell apoptosis as detected 0y
cytometry and assay. Vaccine exposure accompanied 0y
significant increases in the levels of activated caspase <, a key effector
caspase in the apoptosis cascade. Early transcriptional events detected
0y 6(&-"#(. report that hepatitis B vaccine exposure resulted in
significant upregulation of the key genes encoding caspase 5, caspase %,
Inhi0itor caspase-activated (ho-associated coiled-coil
containing protein kinase $ -$/, and protease activating
factor $ -$/. of cleaved caspase <,5 detected 0y
rn 0lot in addition to -$ and caspase % expressions argues
that cell death takes place via the intrinsic apoptotic in
release of cytochrome c from the mitochondria triggers the assem0ly of a
caspase activation complex.
We conclude that e-posure of cells to a low dose of
adEuvanted hepatitis 4 vaccine leads to loss of mitochondrial integrit,"
apoptosis induction" and cell death" apoptosis effect was
also in C0C10 mouse cell line after treated with low dose of
vaccine (=.)" =.1" =.=$ Hg/ml*
. In addition In vivo apoptotic effect of hepatitis B vaccine o0served in
mouse liver.

&himerosal Induces in a astoma 'odel via the cLun -
&erminal Oinase .&oxicological Sciences %9 92;-
8erdman, 'arcelo, F 8uang, (' Dhar S Y Oiningham OO.
Department of "harmacology, Loan #. School of 'edicine, $=29
SpringValley Drive, 'arshall 8untington,
In recent years, controversy has surrounded the use of thimerosal in
vaccines as mercury is a neurotoxin and nephrotoxin. Since the
controversy 0egan in the late $%%34s, much of the thimerosal has 0een
removed from vaccines administered to children in the States.
it remains
in some, such as the influen!a vaccine, and is added to multidose vials used
in countries around the Studies concentrating on thimerosal-induced
neurotoxicity are limited, and exposure guidelines, such as those set 0y the
*oodand Drug are 0ased on research methylmercury.
Interestingly, some in vitro and in vivo studies suggest that ethylmercury
may react differently than methylmercury and
$%%3G 8arry et al., 9332G 'agos et al., $%:=/. studies thimerosal
have focused on determining specific signaling involved in
neurotoxicity. Esta0lishing these may 0e an important step in
discovering methods of alleviating toxic outcomes in patients exposed to
study is the first demonstration that thimerosal can induce
the activation of and -$ in the SO- -S8 neuro0lastoma cell line.
that activation of cLun and -$ transcriptional activity
thimerosal treatment does not appear to 0e involved in the
induction of apoptosis, as demonstrated the studies using thecLun
dominant negative. *urthermore, a0le to that is an
essential upstream component of this through the use of the
inhi0itor S";33$9=. &his compound a0le to attenuate activation of
components of mitochondrial-mediated cell death and
su0se6uently protect the cells from apoptosis. &hese results are significant
0ecause identifying specific signaling activated in response to
thimerosal exposure presents pharmacological targets for attenuating
potential toxicity in patients exposed to thimerosal-containing products.
!'.
'aternal thimerosal exposure results in a0errant cere0ellar oxidative stress,
thyroid hormone meta0olism, and motor 0ehavior in rat pupsG sex- and
strain-dependent effects.#ere0ellum. 93$9 -:;. doi+
$3.$335Hs$9<$$-3$$-3<$%-=. , #hen &, 'idha S, Javacki
, Sa7del- E', Department of "sychiatry, 8arvard 'edical School
and Brigham and 8ospital, Boston,

'ethylmercury -8g/ and ethylmercury -8g/ are toxicants
a range of harmful neurological effects in humans and animals.
'et-8g is a recogni!ed trigger of oxidative stress and an endocrine disruptor
impacting neurodevelopment, the developmental neurotoxicity of Et-8g, a
meta0olite of thimerosal has not 0een explored. hypothesi!ed that
&' exposure during the perinatal period impairs central nervous system
development, and specifically the cere0ellum, 0y the mechanism involving
oxidative stress. &o test this, spontaneously hypertensive rats or
Sprague- rat dams exposed to &' RgHkg 0ody
during pregnancy -)$=/ and lactation -"$3/. 'ale and
female neonates evaluated for auditory and motor functionG cere0ella
analy!ed for oxidative stress and thyroid meta0olism. &' exposure
resulted in a delayed startle response in SD neonates and decreased motor
learning in S8( male in SD male and in SD female
neonates. &' exposure also resulted in a significant increase
in cere0ellar levels of the oxidative stress marker <-nitrotyrosine in S8(
female and SD male neonates. &he activity of cere0ellar
type 9 deiodinase, responsi0le for local intra-0rain conversion of thyroxine
to the active hormone, <4,<,=-triiodothyronine significantly
decreased in &'-exposedS8( male pups. &his coincided an
increased .3>/ expression of a gene negatively regulated 0y &<, 1df2
suggesting local intracere0ellar &< deficiency.
@ur data thus demonstrate a negative neurodevelopmental impact of
perinatal e-posure which appears to and se-
!#.
&he rise in autism and the role of age at diagnosis.Epidemiology. 933%
-%3. doi+ $3.$3%5HEDE.303$<e<$:$%39d$=.8ert!-
"icciotto I, Department of "u0lic 8ealth Sciences,
of #alifornia, Davis, #alifornia %=;$;, ihpQucdavis.edu

prevalence in #alifornia, 0ased on
individuals eligi0le for state-funded services, rose throughout the
$%%3s. &he extent to this trend is explained 0y changes in age at
diagnosis or inclusion of milder cases has not 0een previously
evaluated.'E&81DS+ cases identified from $%%3
through 933; in data0ases of the #alifornia Department of
Developmental Services, coordinates services for individuals
specific developmental disorders. &he main outcomes population
incident cases younger than age $3 years for each 6uarter, cumulative
incidence 0y age and 0irth year, age-specific incidence rates stratified0y
0irth year, and proportions of diagnoses 0y age across 0irth
years. incidence in children rose throughout the
period. #umulative incidence to = years of age per $3,333 0irths rose
consistently from ;.9 for $%%3 0irths to 29.=for 933$ 0irths. -specific
incidence rates increased most steeply for 9- and <-year olds. &he
proportion diagnosed 0y age = years increased only slightly, from =2> for
$%%3 0irths to ;$> for $%%; 0irths. #hanging age at diagnosis can explain
a $9> increase, and inclusion of milder cases, a =;>
incidence in #alifornia no
sign yet of plateauing. Founger ages at diagnosis, differential
migration, changes in diagnostic criteria, and inclusion of milder cases do
not fully explain the o0served increases. 1ther artifacts have yet to 0e
6uantified, and as a result, the extent to the continued rise represents
a true increase in the occurrence of autism remains unclear.

-dependent translocation of 0iopersistent particles from muscle
to 0rain
Jakir Ohan$,9, #hristophe #om0adijre<,2,=, *ranZois-
Val_rie Itier$,$$,9, *ranZois #hristopher Exley%,
'eriem 'ahrouf-Forgov$,$$,9, Pavier Decrouy$,9, "hilippe 'oretto$3, 1livier
&illement5,:, (omain O and Losette
$ Inserm, : rue du
)_n_ral Sarrail, #r_teil, %23$3, *rance9 "aris Est, *acult_ de
'_decine, : rue du )_n_ral Sarrail, #r_teil, %23$3, *rance< Inserm, -S
%2=, %$ Boulevard de "aris, 5=3$<, *rance2 "ierre
et 'arie #urie, *acult_ de '_decine, $$ Boulevard de "aris, 5=3$<,
*rance= -8", )roupe 8ospitalier "iti_-Salp_trijre, Service
dUImmunologie, $$ Boulevard de "aris, 5=3$<, *rance; -8",
8. 'ondor - #henevier, Service dU8istologie, #entre de (_f_rence
=$ du 'ar_chal de de &assigny,
#r_teil, %2333, *rance5 =;93, de "hysico-#himie des
'at_riaux 9 rue Victor )rignard, Villeur0anne, ;%;99, *rance:
#laude Bernard $, 9 rue Victor )rignard, Villeur0anne,
;%;99, *rance% &he Birchall #entre, -Lones Oeele
Staffordshire, S&= =B), =5%5, #entre
d4Etudes de Bordeaux )radignan, du haut Vignaud,
)radignan, <<$5=, *rance$$ *acult_ des Sciences et &echnologie, ;$
du )_n_ral de )aulle, #r_teil, *rance$9 I'(B &eam $3, *acult_ de
'_decine, : rue du )_n_ral Sarrail, #r_teil, *-%23$3, *ranceB'# 'edicine 93$<,
$$+%% doi+$3.$$:;H$52$-53$=-$$-%%, 2
93$< -term 0iodistri0ution of nanomaterials
used in medicine is largely
&his is the case for alum, the most used vaccine ad7uvant, is
a nanocrystalline compound spontaneously forming micronHsu0micron-
si!ed agglomerates. generally tolerated, alum is occasionally
detected monocyte-lineage cells long after immuni!ation in
presuma0ly suscepti0le individuals systemicHneurologic
manifestations or autoimmune syndrome induced 0y
ad7uvants the grounds of preliminary investigations in
9=9 patients alum-associated 0oth a selective
increase of circulating the ma7or monocyte chemoattractant,
and a variation in the gene, designed mouse experiments to assess
0iodistri0ution of vaccine-derived aluminum and of alum-particle
fluorescent surrogates in7ected in muscle. detected in
tissues 0y 'orin stain and particle induced P-ray emission/ Both =33
nm fluorescent latex 0eads and vaccine alum agglomerates-si!ed
nanohy0rids -(ho/ used.(esults+Intramuscular in7ection of alum-
containing vaccine associated the appearance of aluminum
deposits in distant organs, such as spleen and 0rain they still
detected one year after in7ection. Both fluorescent materials in7ected into
muscle translocated to draining lymph nodes and thereafter
detected associated phagocytes in 0lood and spleen. "articles linearly
accumulated in the 0rain up to the six-month endpointG they first
found in perivascular #D$$0T cells and then in microglia and other neural
cells. a0lation dramatically reduced the 0iodistri0ution. #ere0ral
translocation not o0served after direct intravenous in7ection, 0ut
significantly increased in mice chronically altered 0lood-0rain-0arrier.
-of-function experiments consistently implicated in
systemic diffusion of -(ho particles captured 0ymonocyte-lineage cells
and in their su0se6uent neurodelivery. Stereotactic particle in7ection
pointed out 0rain retention as a factor of progressive particle
can 0e transported 0y monocyte-
lineage cells to 0lood and spleen, and, similarly to 8IV, may use
-dependent mechanisms to penetrate the 0rain. &his occurs at a very
rate in normal conditions explaininggood overall tolerance of alum
despite its strong neurotoxic potential. continuously escalating
doses of this poorly 0iodegrada0le ad7uvant in the population may 0ecome
insidiously unsafe, especially in the case of overimmuni!ation or
immatureHaltered 0lood 0rain 0arrier or high constitutive -9
production.

&himerosal and autismK plausi0le hypothesis that should not 0e
dismissed.'ed 8ypotheses. -%2.Blaxill '*,
Bernard S.
&he autism-mercury hypothesis first descri0ed 0y Bernard et al. has
generated much interest and controversy. &he Institute of 'edicine
the connection mercury-containing vaccines and
neurodevelopmental disorders, including autism. &hey concluded that the
hypothesis 0iologically plausi0le 0ut that there insufficient
evidence to accept or re7ect a causal connection and recommended a
comprehensive research program. citing experimental
evidence, a num0er of o0servers have offered opinions on the su07ect,
some of re7ect the I1'4s conclusions. In a recent and
Bauman argue that a link the preservative thimerosal, the source of
the mercury in childhood vaccines, is impro0a0le. In their defense of
thimerosal, these authors take a of the original hypothesis,
provide no evidence, and rely on selective citations and
reasoning. provide evidence here to refute the and Bauman
criti6ue and to defend the autism-mercury hypothesis.

Spectrum Disorders in (elation to Distri0ution of
8a!ardous "ollutantsin the S* Bay Environmental 8ealth
"erspectives Vol. $$2 %, Septem0er, 933;)ayle Div. of
Environmental and 1ccupational Disease #ontrol, #alifornia Department of
8ealth Services9:2 children Y ;=5 controls, 0orn in $%%2 in Bay
assigned exposure levels 0y 0irth tract for $% chemicals. (isks
for autism elevated 0y=3> in tracts the highest chlorinated
solvents and heavy metals. &he highest risk compounds mercury,
cadmium, nickel, trichloroethylene, and vinyl chloride, and the risk from
heavy metals almost as high as solvents.Excerpt+ b1ur results
suggest a potential association autism and estimated metal
concentrations, and possi0ly solvents, in am0ient air around the 0irth


Inflammatory (esponses to &rivalent Influen!a Virus Vaccine
"regnant enVaccine. 93$$ -5. doi+
$3.$3$;H7.vaccine.93$$.3%.3<%. Epu0 93$$ Sep 99.#hristian Iams LD,
"orter O, )laser (.Department of "sychiatry, &he 1hio State
'edical #enter, #olum0us, 18
107ectiveIn the seasonal trivalent influen!a vaccination is
currently universally recommended for all pregnant data
on the maternal inflammatory response to vaccination is lacking and
0etter delineate the safety and clinical utility of immuni!ation. In addition,
for research purposes, vaccination has 0een used as a mild immune trigger
to examine in vivo inflammatory responses in nonpregnant adults. &he
utility of such a model in pregnancy is )iven the clinical and
empirical 7ustifications, the current study examined the magnitude, time
course, and variance in inflammatory responses seasonal
influen!a virus vaccination among pregnant
assessed prior to and at one day days or
approximately one &IV. Serum interleukin -
;, tumor necrosis factor - #-reactive protein and
macrophage migration inhi0itory factor determined 0y high
sensitivity immunoassay.(esultsSignificant increases in #(" seen at one
and days post-vaccination similar effect seen for
- for an increase at days post-vaccination approached
statistical significance A .3;/. &here considera0le varia0ility in
magnitude of responseG coefficients of variation for change at days
post-vaccination ranged from $99> to 59:>, the greatest varia0ility in
-; responses at this timepoint.#onclusions&rivalent influen!a virus
vaccination elicits a measura0le inflammatory response among pregnant
&here is sufficient varia0ility in response for testing associations
clinical outcomes. adverse perinatal health outcomes including
preeclampsia and preterm 0irth have an inflammatory component, a
tendency greater inflammatory responding to immune triggers may
predict risk of adverse outcomes, providing insight into 0iological
mechanisms underlying risk. &he inflammatory response elicited 0y
vaccination is su0stantiallymilder and more transient than seen in infectious
illness, arguing for the clinical value of vaccination. further
research is needed to confirm that the mildinflammatory response elicited
0y vaccination is 0enign in pregnancy

Elevated maternal #-reactive protein and autism in a national 0irth cohort.'ol
"sychiatry. 93$< Lan 99. doi+
Sourander 8inkka-Fli- S, 'cOeague Sundvall L, Surcel
8'.Department of "sychiatry, #olum0ia #ollege of "hysicians and
Surgeons, Fork State "sychiatric Institute, Fork,
Department of Epidemiology, #olum0ia 'ailman School of
"u0lic 8ealth, Fork,
is a complex neuropsychiatric syndrome a
largely etiology. Inflammation during pregnancy may
represent a common 0y infections and other insults increase
risk for the disorder. 8ence, investigated the association early
gestational #-reactive protein an esta0lished inflammatory
0iomarker, prospectively assayed in maternal sera, andchildhood autism in
a large national 0irth cohort an extensive serum 0io0ank. 1ther
strengths of the cohort included nearly complete ascertainment
of pregnancies in *inland million/ over the study period and
national psychiatric registries consisting of virtually all treated autism cases
in the population. Increasing maternal #(" levels, classified as a continuous
varia0le, significantly associated autism in offspring. *or
maternal #(" levels in the highest 6uintile, compared the
6uintile, there a significant, 2<> elevated risk. &his finding suggests
that maternal inflammation may have a significant role in autism,
possi0le implications for identifying preventive strategies and pathogenic
mechanisms in autism and other neurodevelopmental disorders.'olecular
"sychiatry advance online pu0lication, 99 Lanuary 93$<G
doi+$3.$3<:Hmp.93$9.$%5.

is regressive autism and does it occurK Is it the conse6uence of
multi-systemic dysfunction affecting the elimination of heavy metals and
the a0ility to regulate neural temperatureK L 'ed Sci. 933% LulyG
9/+ E. 8ealthcare,
Oingdom &here is a compelling argument that the occurrence of
regressive autism is attri0uta0le to genetic and chromosomal a0normalities,
arising from the overuse of vaccines, su0se6uently affects the
sta0ility and function of the autonomic nervous system and physiological
systems. &hat sense perception is linked to the autonomic nervous system
and the function of the physiological systems ena0les us to examine the
significance of autistic symptoms from a systemic perspective. *ailure of
the excretory system influences elimination of heavy metals and facilitates
their accumulation and su0se6uent manifestation as neurotoxins+ the long-
term conse6uences of lead to neurodegeneration, cognitive
and developmental pro0lems. It may also influence regulation of neural
hyperthermia. &his article explores the issues and concludes that sensory
dysfunction and systemic failure, manifested as autism, is the inevita0le
conse6uence arising from su0tle alteration and conse6uently from the
overuse of vaccines.

adverse events vaccination"rog 8ealth Sci 93$9, Vol
9 , D.`, - B., "as!ko-"ate7
).Department of "ediatric (eha0ilitation of the 'edical of
Bialystok, "oland &he present summari!es data on
neurological adverse events vaccination in the relation to
intensity, time of onset, taking into account the immunological and non-
immunological mechanisms. &he authors descri0ed the physiological
development of the immune system and the possi0le immune system
responses fol vaccination. &oxic property of thimerosal - a mercury-
containing preservative used in some vaccines presented. &he
neurological complications after vaccination descri0ed. &he role of
vaccination in the natural course of infectious diseases and the current
immuni!ations schedule in "oland discussed.

Immunological and autoimmune considerations of Spectrum
Disorders.L 93$< Lul $=. pii+ S3:%;-:2$ -=.
doi+ $3.$3$;H7.7aut.93$<.3=.33=.)esundheit B, L", D,
B, Jachor "roch[!ka V, 'elamed ', Oristt Stein0erg
Shulman #, ", Ooren ), L(,
&amou!a (, ', *arge-Bancel D, ".Lerusalem,
Israel. Spectrum Disorders are a group of
heterogeneous neurodevelopmental conditions presenting in early
childhood a prevalence ranging from 3.5> to 9.;2>. Social interaction
and communication skills are impaired and children often present
unusual repetitive 0ehavior. &he condition persists for life ma7or
implications for the individual, the family and the entire health care system.
the etiology of remains various clues suggest a
possi0le association altered immune responses and
Inflammation in the 0rain and has 0een reported 0y several
groups nota0le microglia activation and increased cytokine
production in postmortem 0rain specimens of young and old individuals
'oreover several la0oratories have isolated distinctive 0rain and
reactive anti0odies from individuals population
0ased epidemiological studies have esta0lished a correlation
and a family history of autoimmune diseases, associations '8# complex
haplotypes, and a0normal levels of various inflammatory cytokines and
immunological markers in the 0lood. In addition, there is evidence that
anti0odies that are only present in some mothers
of children 0ind to fetal 0rain proteins and may 0e a marker or
risk factor for Studies involving the in7ection of these specific
maternal serum anti0odies into pregnant mice during gestation, or
gestational exposure of (hesus monkeys to Ig) su0class of these anti0odies,
have consistently elicited 0ehavioral changes in offspring that have
relevance to summari!e the various types of studies
associating the immune system, critically evaluate the 6uality of
these studies, and attempt to integrate them in a that clarifies the areas
of immune and autoimmune phenomena in research that 0e
important indicators for future research.

Identification of )ene Expression "rofile in #hildren
(egressive Spectrum Disorder and Ileocolitis
e=:3=:. SL,
*ortunato L, )on!ale! Origsman )astrointestinal symptoms
are common in children autism spectrum disorder and are
often associated mucosal inflammatory infiltrates of the small and
large intestine. distinct histologic and immunohistochemical
properties of this inflammatory infiltrate have 0een previously descri0ed in
this group, molecular characteri!ation of these lesions has not 0een
reported. In this study utili!e transcriptome profiling of gastrointestinal
mucosal 0iopsy tissue from children and three non- control
groups disease, ulcerative colitis, and histologically normal/ in
aneffort to determine if there is a gene expression profile uni6ue to the
group. #omparison of differentially expressed transcripts
the groups demonstrated that non-pathologic tissue segregated
almost completely from inflamed tissue in all cases. )ene expression profiles
in intestinal 0iopsy tissue from patients #rohn4s disease, ulcerative
colitis, and having significant overlap each other, also
distinctive features for each group.
+aken together" these results demonstrate that children have a
gastrointestinal mucosal molecular profile that overlaps significantl,
with known inflammator, disease (<45*" ,et has distinctive
features that further supports the presence of an <45
variant" or" alternativel," a prodromal phase of t,pical inflammator,
disease.
report 6"#( confirmation of representative differentially
expressed transcripts determined initially 0y microarray, these findings may
0e considered preliminary to the extent that they re6uire further
confirmation in a validation cohort.

l immune response to 0rain tissue antigen in the
syndrome of autism. L "sychiatry. $%:9
-=.
(, S!ekely 8, E. #ell-
mediated immune response to human myelin 0asic protein studied 0y
the macrophage migration inhi0ition factor test in $5 autistic patients and a
control group of $$ patients suffering from other mental diseases included
in the differential diagnosis of the syndrome of autism. 1f the $5 autistic
patients, $< demonstrated inhi0ition of macrophage migration,
none of the nonautistic patients such a response.
+he results indicate the e-istence of a immune response
to tissue in the s,ndrome of autism
.
'=.
Detection and se6uencing of measles virus from peripheral mononuclear
cells from patients inflammatory disease and autism.Dig Dis
Sci. 9333 - 8, 'ori &, F,
&akekuma O, 8oshika of "aediatrics, &okyo
'edical Lapan. It has 0een reported that measles virus
may 0e present in the intestine of patients #rohn4s disease.
a syndrome has 0een reported inchildren autism
exhi0ited developmental regression and gastrointestinalsymptoms
enterocolitis/, in some cases soon after ''( vaccine. It is not
the virus, if confirmed to 0e present in these patients, derives from
either strains or vaccine strains. In order to characteri!e the strains
thatmay 0e present, have carried out the detection of measles genomic
in peripheral mononuclear cells in eight patients #rohn4s
disease, three patients ulcerative colitis, and nine children autistic
enterocolitis. controls, examined healthy children and
patients SS"E, 8IV-$ total of eight cases/.
purified from "B'# 0y *icoll-pa6ue, 0y reverse transcription using
su07ected to nested "#( for detection of specific
regions of the hemagglutinin and fusion gene regions. "ositive
samples se6uenced directly, in nucleotides :<%<-:;5; region/ or
=<9=-=2;= noncoding * to coding * region/. 1ne of eight patients
#rohn disease, one of three patients ulcerative colitis, and three of
nine children autism, positive. #ontrols all negative. &he
se6uences o0tained from the patients #rohn4s disease shared the
characteristics -strain virus.
+he from the patients with ulcerative colitis and
children with autism were consistent with vaccine strains.
&he results concordant the exposure history of the patients.
"ersistence of measles virus confirmed in "B'# in some patients
chronic intestinal inflammation.
'1.
'echanisms of aluminum ad7uvant toxicity and autoimmunity in pediatric
populations 93$9 -<3. doi+
&oml7enovic,
Dynamics (esearch )roup, Department of 1phthalmology and Visual
Sciences, of British #olum0ia, Vancouver, B#,
#anadaDepartments of 1phthalmology and Visual Sciences and
Experimental 'edicine and the )raduate "rogram in
of British #olum0ia, Vancouver, B#,
&oml7enovic, "ost-doctoral Dynamics (esearch )roup,
Department of 1phthalmology and Visual Sciences, of British
#olum0ia stractImmune challenges during early development,
including those vaccine-induced, can lead to permanent detrimental
alterations of the 0rain and immune function. Experimental evidence also
that simultaneous administration of as little to three immune
ad7uvants can overcome genetic resistance to autoimmunity. In some
developed countries, 0y the time children are 2 to ; years old, they have
received a total of $9; antigenic compounds along high amounts of
aluminum ad7uvants through routine vaccinations. to the
*ood and Drug safety assessments for vaccines have
often not included appropriate toxicity studies 0ecause vaccines have not
0een as inherently toxic. &aken together, these o0servations raise
plausi0le concerns a0out the overall safety of current childhood vaccination
programs. assessing ad7uvant toxicity in children, several key points
ought to 0e considered+ infants and children should not 0e as
bsmall regard to toxicological risk as their uni6ue physiology
makes them much more vulnera0le to toxic insultsG in adult humans
vaccine ad7uvants have 0een linked to a variety of serious autoimmune
and inflammatory conditions yet children are regularly
exposed to much higher amounts of from vaccines than adultsG it
is often assumed that peripheral immune responses do not affect 0rain
function.
" it is now clearl, that there isa
that pla,s crucial roles in
immunoregulation as well as function. <n turn"
of the a-is have demonstrated in man,
autoimmune diseases encompassed in FA3<AG and are thought to
driven a h,peractive immune response6 and (iv* the same
components of the a-is that pla, ke, roles in
development and immune functionare heavil, targeted Al
adEuvants.
In summary, research evidence that increasing concerns a0out
current vaccination practices may indeed 0e arranted. Because children
may 0e most at risk of vaccine-induced
complications, a rigorous evaluation of the vaccine-related adverse health
impacts in the pediatric population is urgently needed.
'0.
&hiol-modulated mechanisms of the cytotoxicity of thimerosal and
inhi0ition of topoisomerase II alpha.#hem (es &oxicol. 933:
- P, 8, 148ara L#, 8asinoff
BB.*aculty of "harmacy, of 'anito0a, =3 Sifton (oad,
'anito0a, (<& #anada. &himerosal is an organic mercury
compound that is used as a preservative in vaccines and other
solution formulations. &he use of thimerosal has caused concern a0out its
a0ility to cause neurological a0normalities due to mercury accumulation
during a normal schedule of childhood vaccinations. chemistry
and the 0iological effects of methylmercury have 0een -studied,those of
thimerosal have not. &himerosal reacted rapidly cysteine, )S8, human
serum al0umin, and single-stranded to form ethylmercury adducts
that detecta0le 0y mass spectrometry. &hese results indicated that
thimerosal 0e 6uickly meta0oli!ed in vivo 0ecause of its reactions
protein and nonprotein thiols.
+himerosal also potentl, the decatenation activit, of 5>A
topoisomerase << alpha" likel, through reactionwith critical free
c,steine thiol groups.
&himerosal, did not act as a topoisomerase II poison and the lack
of cross-resistance a O=;9 cell line a decreased level of
topoisomerase II alpha cells/ suggested that inhi0ition of
topoisomerase II alpha not a significant mechanism for the inhi0ition
of cell
5epletion of intracellular with sulfo-imine treatment
greatl, increased the I$!0 cell growth effects of thimerosal"
which showed that intracellular glutathione had a maEor role in
protecting cells from thimerosal.
"retreatment of thimerosal did not, change its
O=;9 cell inhi0itory effects, a result consistent the rapid
exchange of the ethylmercury adduct among various thiol-containing
cellular reactants. &himerosal-induced single and dou0le strand 0reaks in
O=;9 cells consistent a rapid induction of apoptosis.
Inconclusion, these studies have elucidated some of the chemistry and
0iological activities of the interaction of thimerosal topoisomerase II
alpha and protein and nonprotein thiols and
').
&opoisomerases facilitate transcription of long genes linked to
autism doi+$3.$3<:Hnature$9=32(eceived $5 Lanuary
93$< 92 Luly 93$< "u0lished online 9: 93$<
I a n * . O i n g , # h a n d r i F a n d a v a , ' .
' a 0 0 , L a c k S . 8 s i a o , 8si en-Sung 8uang, Brandon
"earson, L. ' auro #al a0rese, L o s h u a
S t a r m e r , L o e l S . " a r k e r ,
& e r r y ' a g n u s o n , S t o r m y L .
#ham0erl ai n, Ben7ami n D. "hi l pot Y ' ark L.
Jyl ka &opoisomerases are expressed throughout the developing
and adult 0rain and are mutated in some individuals autism spectrum
disorder topoisomerases are mechanistically
connected to is 8ere that topotecan, a
topoisomerase $ inhi0itor, dose-dependently reduces the
expression of extremely long genes in mouse and human neurons,
including nearly all genes that are longer than 933kilo0ases.
Expression of long genes is also reduced after of &op$ or
&op90 in neurons, highlighting that 0oth en!ymes are re6uired for full
expression of long genes. By mapping polymerase II density genome-
in neurons, found that this length-dependent effect on gene
expression due to impaired transcription elongation. Interestingly,
many high-confidence candidate genes are exceptionally long and
reduced in expression after &1"$ inhi0ition.
@ur findings suggest that chemicals and genetic mutations that impair
topoisomerases could commonl, to A35 and other
neurodevelopmental disorders.'9.
in the central nervous system toxicity in
humans and animals,
vaccine ad7uvants, and autoimmunity
.Immunol (es. 93$< -</+<32-$;. &oml7enovic
have examined the neurotoxicity of aluminum in humans
and animals under various conditions, different routes of
administration, and provide an of the various associated disease
states. &he literature demonstrates clearly negative impacts of aluminum on
the nervous system across the age span. In adults, aluminum exposure can
lead to apparently age-related neurological deficits resem0ling
and has 0een linked to this disease and to the )uamanian variant, -"D#.
Similar outcomes have 0een found in animal models. In addition, in7ection
of aluminum ad7uvants in an attempt to model )ulf syndrome and
associated neurological deficits leads to an phenotype in young male
mice. In young children, a highly significant correlation exists the
num0er of pediatric aluminum-ad7uvanted vaccines administered and the
rate of autism spectrum disorders. 'any of the features of aluminum-induced
neurotoxicity may arise, in part, from autoimmune reactions, as part of the
syndrome.
'$.
&ranscriptomic of Effects in 'ouse Brain
Intermittent
of &himerosal.&oxicol Sci. 93$2 2. P$,
*, Pie *, 8, Song S, #hen &, Jhang F, Jhu S, ang F, )uo #, &ang
&S. &himerosal is a vaccine antimicro0ial preservative has
long 0een suspected an iatrogenic factor possi0ly contri0uting to
neurodevelopmental disorders including autism. &he association
infant vaccine thimerosal exposure and autism remains an open 6uestion.
thimerosal has 0een removed from mandatory childhood
vaccines in the States, thimerosal-preserved vaccines are still
used outside of the States especially indeveloping countries.
thimerosal-containing vaccines are 0eing given to the
the first $9-92 h after 0irth in some countries. &o examine the
possi0le neurotoxic effects of early neonatal exposure to a higher level of
thimerosal, *VB mice su0cutaneously in7ected thimerosal-
mercury at adose is higher than that used for regular #hinese
infant immuni!ation during the first 2 months of life. &himerosal-treated
mice exhi0ited neural development delay, social interaction deficiency, and
inclination of depression. neuropathological changes
also o0served in adult mice neonatallytreated thimerosal. 8igh-
throughput se6uencing of autistic-0ehaved mice 0rains revealed the
alternation of a num0er of canonical involvingneuronal
development, neuronal synaptic function, and the dysregulation of
endocrine system. Intriguingly, the elevation of anterior pituitary secreting
hormones occurred exclusively in male 0ut not in female thimerosal-treated
mice,demonstrating for the first time the gender 0ias of thimerosal-mercury
toxicity regard to endocrine system. 1ur results indicate that higher
dose of neonatal thimerosal-mercury higher than that used in
human/ is capa0le of inducing long-lasting su0stantial dysregulation of
neurodevelopment, synaptic function, and endocrine system, could
0e the causal involvements of autistic-like 0ehavior in mice.
'!.
#an of 'edical "athophysiology in to "rimary #are
"revention StrategiesK
Eli!a0eth 'umper, 'D, L 'ed Sci. -$22. D1I+
$3.5$=;Hna7ms.93$<.3;3<$<2 Emerging research suggests that
the timing of environmental factors in the presence of genetic
predispositions has influenced the increase in autism spectrum disorders
over the past several decades. of the medical literature suggests
that autism may 0e impacted 0y environmental toxicants, 0reastfeeding
duration, gut flora composition, nutritional status, acetaminophen use,
vaccine practices and use of anti0iotics andHor fre6uency of infections.
&he
author reports her retrospective clinical research in a general pediatric
practice for #hildren/, a modest trend
prevalence of autism than her previous pediatric practice or recent
#D# data. 1ut of 9%2 general pediatrics patients since 933= there
!ero cases of autism value 3.3$2/. )iven the prevalence of
autism for that cohort of $ in =3 children in the States, it is important
to consider implementing strategies in primary care practice that could
potentially modify environmental factors or affect the timing of
environmental triggers contri0uting to autism.

8epatitis B vaccination of male neonates and autism diagnosis,
$%%5-
9339. #', et al. all LournalL &oxicol Environ
8ealth -55. doi+
$3.$3:3H$=9:5<%2.93$3.=$%<$5. hepatitis B
vaccination recommended for in $%%$G
safety findings are mixed. &he association hepatitis B vaccination
of male neonates and parental report of autism diagnosis determined.
&his cross-sectional study used pro0a0ility samples o0tained
from 8ealth Survey $%%5-9339 data sets. Vaccination
status determined from the vaccination record. regression
used to estimate the odds for autism diagnosis associated neonatal
hepatitis B vaccination among 0oys age <-$5 years, 0orn 0efore $%%%,
ad7usted for race, maternal education, and -parent household.
4o,s vaccinated as neonates had threefold greater odds for autism
diagnosis compared to never vaccinated or vaccinated after the
first month of life.
-8ispanic 0oys ;2> less likely to have autism diagnosis
relative to 0oys. *indings suggest that male neonates
vaccinated the hepatitis B vaccine prior to $%%% vaccination
record/ had a threefold higher risk for parental report of autism diagnosis
compared to 0oys not vaccinated as neonates during that same time period.
0oys 0ore a greater risk.