123 research papers supporting the vaccine autism link

8/20/2019 123 Research Papers Supporting the Vaccine Autism Link

1/92

123 Research papers supporting Vaccine/Autism Causation

1. Increased risk of developmental neurologic impairment after high exposure tothimerosal-containing vaccine in first month of life.

Division of Epidemiology and Surveillance, Vaccine Safety and Development

Branch, ational 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 containingpreservative thimerosal in vaccines. e assessed the risk for neurologic andrenal impairment associated ith past exposure to thimerosal-containing vaccineusing automated data from the Vaccine Safety Data link VSD/. VSD is a largelinked data0ase from four health maintenance organi!ations in ashington,1regon and #alifornia, containing immuni!ation, medical visit and demographicdata on over 233,333 infants 0orn 0eteen 4%$ and 4%5.

'ethods+ e categori!ed the cumulative ethylmercury exposure from &himerosalcontaining vaccines after one month of life and assessed the su0se6uent risk ofdegenerative and developmental neurologic disorders and renal disorders 0eforethe age of six. e applied proportional ha!ard models ad7usting for 8'1, year of 0irth, and gender, excluding premature 0a0ies.

(esults+ e identified 9:; children ith degenerative and


2/92

&oxicol Environ 8ealth . 93$3F5


3/92

selective toxicity of thimerosal and indicate that any future studies of thimerosaltoxicity should take into consideration gender-specific differences.

4. 'ercury toxicokinetics--dependency on strain and gender.

&oxicol ppl "harmacol. 93$3 'ar $=F92


4/92

0stractAutism spectrum disorder A64+ is over four times more prevalent in malescompared to females. Increased understanding of sex differences in SDendophenotypes could add insight into possi0le etiologies and the assessmentand management of the disorder. #onse6uently, the purpose of this revie is to

descri0e current literature regarding sex differences in the developmental,psychiatric, and medical endophenotypes of SD in order to illustrate currentknoledge and areas in need of further research. 1ur revie found that repetitive0ehaviors and restricted interests are more common in males than females ith

SD. Intellectual disa0ility is more common in females than males ith SD. ttention to detail may 0e more common in males than females ith SD andepilepsy may 0e more common in females than males ith SD, although limitedresearch in these areas prevent definitive conclusions from 0eing dran. &heredoes not appear to 0e a sex difference in other developmental, psychiatric, andmedical symptoms associated ith SD, or the research as contradictory or toosparse to esta0lish a sex difference. 1ur revie is uni6ue in that it offers detaileddiscussion of sex differences in three ma7or endophenotypes of SD. *urther

research is needed to 0etter understand hy sex differences exist in certain SDtraits and to evaluate hether phenotypic sex differences are related to differentpathays of development, assessment, and treatment of the disorder.

6. Do aluminum vaccine ad7uvants contri0ute to the rising prevalence of autismO

Inorg Biochem. 93$$ ovF$3=$$/+$2:%-%%. Epu0 93$$ ug 9


5/92

o0served over the last to decades "earson rA3.%9, pQ3.333$/F and iii/ asignificant correlation exists 0eteen the amounts of l administered topreschool children and the current prevalence of SD in seven esterncountries, particularly at


6/92

8. luminum-Induced Entropy in Biological Systems+ Implications for eurologicalDisease

ournal of &oxicology, Volume 93$2 93$2/, rticle ID 2%$


7/92

administered";

%. comparison of temporal trends in Hnited States autism prevalence to trends insuspected environmental factors

Environ 8ealth. 93$2F $


8/92

decreased over this same time frame. Environmental factors ith increasingtemporal trends can help suggest hypotheses for drivers of autism that meritfurther investigation.

$3. utism+ a form of lead and mercury toxicity

Environ &oxicol "harmacol. 93$2 ovF


9/92

Eleonor BH(1#L-BHS#8,a 1mnia (. 'I,0 8ani 8. DESS1LI,c and&hanaa (B8 daecturer and dvisor, International Board of #linical 'etal &oxicology )erman'edical ssociation of #linical 'etal &oxicology, 8ers0ruck, )ermany0ssociate "rofessor of "sychiatry, #airo Hniversity, Egypt

cssociate "rofessor of "sychiatry, Beni-Suef Hniversity, Egypt - Beni-SuefHniversityd(esearcher of "u0lic 8ealth and Biostatistics, ational (esearch #enter, Egypt

ddress for correspondence+ Eleonor Blaurock-Busch, a0oratory for #linicaland Environmental nalyses. (o0enstr 93, D-%$99$5, 8ers0ruck, )ermania."hone+ W332% %$=$2


10/92

0stract&he interactions 0eteen genes and the environment are no regarded as themost pro0a0le explanation for autism. In this revie, e summari!e the results of a metallomics study in hich scalp hair concentrations of 9; trace elements ereexamined for $,%;5 autistic children $,==< males and 2$2 females aged 3-$=

years-old/, and discuss recent advances in our understanding of epigenetic rolesof infantile mineral im0alances in the pathogenesis of autism. In the $,%;5su07ects, =:2 9%.5>/ and / ere found deficient in !inc andmagnesium, respectively, and the incidence rate of !inc deficiency as estimatedat 2 in male and =9.=> in female infantile su07ects aged 3-< years-old. Incontrast, / and %2 2.:>/ individuals ere found to sufferfrom high 0urdens of aluminum, cadmium and lead, respectively, and 9.:> orless from mercury and arsenic. 8igh toxic metal 0urdens ere more fre6uentlyo0served in the infants aged 3-< years-old, hose incidence rates ere 93.;>,$9.$>, 5.=>, and 9. for aluminum, cadmium, lead, arsenic and mercury,respectively. &hese findings suggest that infantile !inc- and magnesium-deficiency andGor toxic metal 0urdens may 0e critical and induce epigenetic

alterations in the genes and genetic regulation mechanisms ofneurodevelopment in the autistic children, and demonstrate that a time factorPinfantile indoP is also critical for neurodevelopment and pro0a0ly for therapy.&hus, early metallomics analysis may lead to early screeningGestimation andtreatmentGprevention for the autistic neurodevelopment disorders.

13. 0normal measles-mumps-ru0ella anti0odies and #S autoimmunity in childrenith autism.

Biomed Sci. 9339 ul-ugF%2/+


11/92

over %3> of ''( anti0ody-positive autistic sera ere also positive for 'B"autoanti0odies, suggesting a strong association 0eteen ''( and #Sautoimmunity in autism. Stemming from this evidence, e suggest that aninappropriate antiod- response to 55R$ specificall- the measlescomponent thereof$ might e related to pathogenesis of autism"

14. Infection, vaccines and other environmental triggers of autoimmunity.

utoimmunity. 933= 'ayF


12/92

&heresa . Deisher, goc V. Doan, ngelica 1maiye, Lumiko Loyama, SarahBa0ye

0stract&he aim of this study as to investigate a previously overlooked, universallyintroduced environmental factor, fetal and retroviral contaminants in childhood

vaccines, a0sent prior to change points #"s/ in autistic disorder D/prevalence ith su0se6uent dose-effect evidence and knon pathologicmechanisms of action. orldide population 0ased cohort study as used forthe design of this study. &he Hnited States, estern ustralia, Hnited Lingdomand Denmark settings ere used. ll live 0orn infants ho later developedautistic disorder delivered after $ anuary $%53, hose redacted vaccination andautistic disorder diagnosis information is pu0licly availa0le in data0asesmaintained 0y the HS *ederal )overnment, estern ustralia, HL, andDenmark. &he live 0irths, grouped 0y fatherTs age, ere from the HS and

ustralia. &he children vaccinated ith ''(II, Varicella and 8epatitis vaccinesvaried from $% to


13/92

933$ and 9335 as determined. positive and statistically significant relationshipas found+ &he higher the proportion of children receiving recommendedvaccinations, the higher as the prevalence of H& or SI. $> increase invaccination as associated ith an additional ;:3 children having H& or SI.either parental 0ehavior nor access to care affected the results, sincevaccination proportions ere not significantly related statistically/ to any other

disa0ility or to the num0er of pediatricians in a H.S. state. ,he results suggestthat although mercur- has een removed from man- vaccines$ otherculprits ma- link vaccines to autism" *urther study into the relationship0eteen vaccines and autism is arranted. &o read the a0stract click 8E(E.

17. eonatal administration of a vaccine preservative, thimerosal, produces lastingimpairment of nociception and apparent activation of opioid system in rats.

Brain (es. 933% Dec :F$


14/92

&oxicol Sci. 93$2 unF$


15/92

postnatal administration of thimerosal four i.m. in7ections, $9 or 923 Zg &8I'-8gGkg, on postnatal days 5, %, $$ and $=/ on 0rain pathology in istar rats.umerous neuropathological changes ere o0served in young adult rats hichere treated postnatally ith thimerosal. &hey included+ ischaemic degenerationof neurons and PdarkP neurons in the prefrontal and temporal cortex, thehippocampus 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 effectsof thimerosal$ at doses e0uivalent to those used in infant vaccines orhigher$ in developing rat rain$ suggesting likel- involvement of thismercurial in neurodevelopmental disorders"

20. "ersistent 0ehavioral impairments and alterations of 0rain dopamine system after early postnatal administration of thimerosal in rats.

Behav Brain (es. 93$$ Sep


16/92

21. B-ymphocytes from a "opulation of #hildren ith utism Spectrum Disorder and&heir Hnaffected Si0lings Exhi0it 8ypersensitivity to &himerosal

&oxicol. 93$ of controls. #ells hypersensitive to thimerosalalso had higher levels of oxidative stress markers, protein car0onyls, and oxidantgeneration. ,his suggests certain individuals with a mild mitochondrialdefect ma- e highl- susceptile to mitochondrial specific to.ins like the

vaccine preservative thimerosal"

22. &himerosal-Derived Ethylmercury Is a 'itochondrial &oxin in 8uman strocytes+"ossi0le (ole of *enton #hemistry in the 1xidation and Breakage of mtD

&oxicol. 93$9F 93$9+


17/92

generated h-dro.-l radical" ,hese o.idants increase the levels of cellularaldeh-de/ketones" Additionall-$ we find a five*fold increase in the levels ofo.idant damaged mitochondrial 4GA ases and increases in the levels ofmt4GA nicks and lunt*ended reaks" 9ighl- damaged mitochondria arecharacteri8ed - having ver- low memrane potentials$ increasedsupero.ide/h-drogen pero.ide production$ and e.tensivel- damaged

mt4GA and proteins" ,hese mitochondria appear to have undergone apermeailit- transition$ an oservation supported - the five*fold increasein Caspase*3 activit- oserved after ,himerosal treatment"

23. &hioredoxin+ novel, independent diagnosis marker in children ith autism.

Int Dev eurosci. 93$2 ov 9;. pii+ S35


18/92

Biol #hem. 933: 'ay 9F9:


19/92

antioxidants, such as )S8, and clinically used exogenous chelating agents B,D'"S, D'S, and ^-lipoic acid. #onsistent ith the in vitro results, recovery of&rx( activity and cell via0ility 0y selenite as o0served in 8g#l9/-treated 8EL9%< cells. &hese results stress the role of &rx( as a target of mercurials andprovide the mechanism of selenite as a detoxification agent for mercurypoisoning.

26. Serological association of measles virus and human herpesvirus-; ith 0rainautoanti0odies in autism.

#lin Immunol Immunopathol. $%%: 1ctF:%$/+$3=-:.

Singh VL, in S, Rang V#. #ollege of "harmacy, Hniversity of 'ichigan, nn r0or, 'ichigan, 2:$3%-$3;=, HS.

Astract#onsidering an autoimmunity and autism connection, 0rain autoanti0odies tomyelin 0asic protein anti-'B"/ and neuron-axon filament protein anti-*"/have 0een found in autistic children. In this current study, e examinedassociations 0eteen virus serology and autoanti0ody 0y simultaneous analysisof measles virus anti0ody measles-Ig)/, human herpesvirus-; anti0ody 88V-;-Ig)/, anti-'B", and anti-*". e found that measles-Ig) and 88V-;-Ig) titersere moderately higher in autistic children 0ut they did not significantly differfrom normal controls. 'oreover, e found that a vast ma7ority of virus serology-positive autistic sera as also positive for 0rain autoanti0ody+ i/ %3> of measles-Ig)-positive autistic sera as also positive for anti-'B"F ii/ 5 of measles-Ig)-positive autistic sera as also positive for anti-*"F iii/ :2> of 88V-;-Ig)-

positive autistic sera as also positive for anti-'B"F and iv/ 59> of 88V-;-Ig)-positive autistic sera as also positive for anti-*". ,his stud- is the first toreport an association etween virus serolog- and rain autoantiod- inautismH it supports the h-pothesis that a virus*induced autoimmuneresponse ma- pla- a causal role in autism"

27. 'eta0olic 0iomarkers of increased oxidative stress and impaired methylationcapacity in children ith autism

merican ournal of #linical utrition, Vol. :3, o. ;, $;$$-$;$5, Decem0er 9332

Department of "ediatrics, Hniversity of rkansas for 'edical Sciences, and the rkansas #hildren4s 8ospital (esearch Institute

0stractBackground+ utism is a complex neurodevelopmental disorder that usuallypresents in early childhood and that is thought to 0e influenced 0y genetic and

http://www.ncbi.nlm.nih.gov/pubmed/9756729http://www.ncbi.nlm.nih.gov/pubmed/9756729http://www.ncbi.nlm.nih.gov/pubmed/9756729http://www.ncbi.nlm.nih.gov/pubmed?term=Singh%20VK%5BAuthor%5D&cauthor=true&cauthor_uid=9756729http://www.ncbi.nlm.nih.gov/pubmed?term=Lin%20SX%5BAuthor%5D&cauthor=true&cauthor_uid=9756729http://www.ncbi.nlm.nih.gov/pubmed?term=Yang%20VC%5BAuthor%5D&cauthor=true&cauthor_uid=9756729http://www.ajcn.org/content/80/6/1611.fullhttp://www.ajcn.org/content/80/6/1611.fullhttp://www.ncbi.nlm.nih.gov/pubmed/9756729http://www.ncbi.nlm.nih.gov/pubmed/9756729http://www.ncbi.nlm.nih.gov/pubmed/9756729http://www.ncbi.nlm.nih.gov/pubmed?term=Singh%20VK%5BAuthor%5D&cauthor=true&cauthor_uid=9756729http://www.ncbi.nlm.nih.gov/pubmed?term=Lin%20SX%5BAuthor%5D&cauthor=true&cauthor_uid=9756729http://www.ncbi.nlm.nih.gov/pubmed?term=Yang%20VC%5BAuthor%5D&cauthor=true&cauthor_uid=9756729http://www.ajcn.org/content/80/6/1611.fullhttp://www.ajcn.org/content/80/6/1611.full


20/92

environmental factors. lthough a0normal meta0olism of methionine andhomocysteine has 0een associated ith other neurologic diseases, thesepathays have not 0een evaluated in persons ith autism.

107ective+ &he purpose of this study as to evaluate plasma concentrations ofmeta0olites in the methionine transmethylation and transsulfuration pathays in

children diagnosed ith autism.

Design+ "lasma concentrations of methionine, S-adenosylmethionine S'/, S-adenosylhomocysteine S8/, adenosine, homocysteine, cystathionine, cysteine,and oxidi!ed and reduced glutathione ere measured in 93 children ith autismand in


21/92

&o address a possi0le environmental contri0ution to autism, e carried out aretrospective study on urinary porphyrin levels, a 0iomarker of environmentaltoxicity, in 9;% children ith neurodevelopmental and related disorders referred toa "aris clinic 9339N9332/, including $3; ith autistic disorder. Hrinary porphyrinlevels determined 0y high-performance li6uid chromatography ere compared0eteen diagnostic groups including internal and external control groups.

#oproporphyrin levels ere elevated in children ith autistic disorder relative tocontrol groups. Elevation as maintained on normali!ation for age or to a controlheme pathay meta0olite uroporphyrin/ in the same samples. &he elevationas significant " Q 3.33$/. "orphyrin levels ere unchanged in sperger4sdisorder, distinguishing it from autistic disorder. &he atypical moleculeprecoproporphyrin, a specific indicator of heavy metal toxicity, as also elevatedin autistic disorder " Q 3.33$/ 0ut not significantly in sperger4s. su0group ithautistic disorder as treated ith oral dimercaptosuccinic acid D'S/ ith avie to heavy metal removal. *olloing D'S there as a significant " A 3.339/drop in urinary porphyrin excretion. ,hese data implicate environmentalto.icit- in childhood autistic disorder"

29. n investigation of porphyrinuria in ustralian children ith autism.

&oxicol Environ 8ealth . 933:F5$93/+$


22/92

30. "orphyrinuria in Lorean children ith autism+ correlation ith oxidative stress.

&oxicol Environ 8ealth . 93$3F5


23/92

ddress correspondence to I.. "essah, Department of Veterinary 'edicine,'olecular Biosciences, $


24/92

a Department of 'edical 'icro0iology and Immunology, Hniversity of #alifornia,Davis, HS0 &he '.I..D. Institute, Hniversity of #alifornia, Davis, HSc Department of "sychiatry and Behavioral Sciences, Hniversity of #alifornia,Davis, HS

d Division of (heumatology, llergy and #linical Immunology, Hniversity of#alifornia, Davis, HS

0stract&he pathophysiology of autism spectrum disorder SD/ is not yet knonFhoever, studies suggest that dysfunction of the immune system affects manychildren ith SD. Increasing evidence points to dysfunction of the innateimmune system including activation of microglia and perivascular macrophages,increases in inflammatory cytokinesGchemokines in 0rain tissue and #S*, anda0normal peripheral monocyte cell function. Dendritic cells are ma7or players ininnate immunity and have important functions in the phagocytosis of pathogensor de0ris, antigen presentation, activation of na_ve & cells, induction of tolerance

and cytokineGchemokine production. In this study, e assessed circulatingfre6uencies of myeloid dendritic cells defined as in-$`BD#$W#D$$cW andin-$`BD#


25/92

days (ice/, hile thimerosal organic mercury/ once in the 0rain converts toinorganic mercury at much higher rates, and inorganic mercury has a half-life inthe 0rain measured in years and decades (ooney/. &his ork is ground0reaking0ecause little is knon a0out ethyl mercury, and many health authorities haveasserted that the mercury found in vaccines is the Psafe kind.P &his study alsodelivers a strong re0uke of the Institute of 'edicine4s recommendation in 9332 to

no longer pursue the mercury-autism connection.

Excerpt+ P recently pu0lished I1' revie I1' 9332/ appears to havea0andoned the earlier recommendation ?of studying mercury and autism@ as ellas 0ack aay from the merican cademy of "ediatrics goal ?of removingmercury from vaccines@. &his approach is difficult to understand, given ourcurrent limited knoledge of the toxicokinetics and developmental neurotoxicityof thimerosal, a compound that has 0een and ill continue to 0e/ in7ected inmillions of ne0orns and infants.P

Excerpt+ &he average 0rain-to-0lood partitioning ratio of total 8g in thethimerosal group as slightly higher than that in the 'e8g group


26/92

34. &he retention time of inorganic mercury in the 0rain--a systematic revie of theevidence.

&oxicol ppl "harmacol. 93$2 *e0 $F952


27/92

&oxicology (esearch Division, 8ealth "rotection Branch, 8ealth and elfare,1ttaa, 1ntario, #anada.

0stractEstimated half-lives of mercury folloing methylmercury exposure in humans are=9-%< d for hole 0ody and 2%-$;2 d for 0lood. In its most recent $%:3 revie,

the orld 8ealth 1rgani!ation concluded that there as no evidence to suggestthat 0rain half-life differed from hole-0ody half-life. In the present study, femalemonkeys 'acaca fascicularis/ ere dosed for at least $.5 yr ith $3, 9=, or =3microgramsGkg.d of mercury as methylmercuric chloride. Dosing asdiscontinued, and 0lood half-life as determined to 0e a0out $2 d. pproximately9


28/92

ma- e responsile for the increase in reactive glia. ll other cell types,including the neurons, shoed no significant change in num0er at the prescri0edexposure level and durations. &he identities of the reactive glial cells and theimplications for the long-term function and surviva0ility of the neurons due tochanges in the glial population folloing su0clinical long-term exposure tomercury are discussed.

37. euroglial ctivation and euroinflammation in the Brain of "atients ith utism

nnals of eurology, *e0 933=.

Diana . Vargas, 'D, ohns 8opkins Hniversity.

0stract utism is a neurodevelopmental disorder characteri!ed 0y impairedcommunication and social interaction and may 0e accompanied 0y mental

retardation and epilepsy. Its cause remains unknon, despite evidence thatgenetic, environmental, and immunological factors may play a role in itspathogenesis. &o investigate hether immune-mediated mechanisms areinvolved in the pathogenesis of autism, e used immunocytochemistry, cytokineprotein arrays, and en!yme-linked immunosor0ent assays to study 0rain tissuesand cere0rospinal fluid #S*/ from autistic patients and determined themagnitude of neuroglial and inflammatory reactions and their cytokine expressionprofiles. Brain tissues from cere0ellum, midfrontal, and cingulate gyrus o0tainedat autopsy from $$ patients ith autism ere used for morphological studies.*resh-fro!en tissues availa0le from seven patients and #S* from six livingautistic patients ere used for cytokine protein profiling. e demonstrate anactive neuroinflammatory process in the cere0ral cortex, hite matter, and

nota0ly in cere0ellum of autistic patients. Immunocytochemical studies shoedmarked activation of microglia and astroglia, and cytokine profiling indicated thatmacrophage chemoattractant protein '#"/-$ and tumor groth factor-0eta$,derived from neuroglia, ere the most prevalent cytokines in 0rain tissues. #S*shoed a uni6ue proinflammatory profile of cytokines, including a markedincrease in '#"-$. 1ur findings indicate that innate neuroimmune reactions playa pathogenic role in an undefined proportion of autistic patients, suggesting thatfuture therapies might involve modifying neuroglial responses in the 0rain.

Excerpt+ Pecause this neuroinflammator- process appears to eassociated with an ongoing and chronic mechanism of CG6 d-sfunction$potential therapeutic interventions should focus on the control of its

detrimental effects and there- eventuall- modif- the clinical course ofautism.P


29/92

ature #ommunications =, rticle num0er+ =52: doi+$3.$3


30/92

aluminum-affected genes, and 5G: :5.=>/ of aluminum-induced genes exhi0itexpression patterns similar to those o0served in D. &he seven genes found to0e significantly up-regulated 0y aluminum encode pro-inflammatory or pro-apoptotic signaling elements, including *-kappaB su0units, interleukin-$0etaprecursor, cytosolic phospholipase 9, cyclooxygenase-9, 0eta-amyloidprecursor protein and D, a regulatory protein knon to induce apoptosis and

repress transcription. ,he promoters of genes up*regulated - aluminum areenriched in inding sites for the stress*inducile transcription factors 9F*1and GF*kappa$ suggesting a role for aluminum$ 9F*1 and GF*kappa indriving at-pical$ pro*inflammator- and pro*apoptotic gene e.pression" &heeffect of aluminum on specific stress-related gene expression patterns in human0rain cells clearly arrant further investigation.

23. 0errant *-kappaB expression in autism spectrum condition+ a mechanism forneuroinflammation.

*ront "sychiatry. 93$$ 'ay $


31/92

especiall- of resident immune cells in rain regions associated with theehavioral and clinical s-mptoms of A6C"

2$. Study of uclear &ranscription *actor-Lappa B in #hildhood utism

"oS 1ne. 93$$F ;=/+ e$%2::.

Hsha S. aik,$ #haritha )angadharan,9 Lanakalatha 00agani,$ Balakrishnaagalla,< iran7an Dasari,$ and Sunil L. 'anna9,['onica Hddin, Editor

Department of "sychiatry, 1smania 'edical #ollege, 8ydera0ad, Indiaa0oratory of Immunology, #entre for D *ingerprinting and Diagnostics,ampally, 8ydera0ad, Indiaational Institute of utrition, 8ydera0ad, India

Hniversity of 'ichigan, Hnited States of merica

0stractBackgroundSeveral children ith autism sho regression in language and socialdevelopment hile maintaining normal motor milestones. clear period of normaldevelopment folloed 0y regression and su0se6uent improvement ithtreatment, suggests a multifactorial etiology. &he role of inflammation in autism isno a ma7or area of study. Viral and 0acterial infections, hypoxia, or medicationcould affect 0oth foetus and infant. &hese stressors could upregulatetranscription factors like nuclear factor kappa B *-B/, a master sitch formany genes including some implicated in autism like tumor necrosis factor

&*/. 1n this hypothesis, it as proposed to determine *-B in children ithautism.

'ethods"eripheral 0lood samples of ;5 children ith autism and 9% control children ereevaluated for *-B using electrophoretic mo0ility shift assay E'S/. phosphor imaging techni6ue as used to 6uantify values. &he fold increase overthe control sample as calculated and statistical analysis as carried out usingS"SS $=.

(esultse have noted significant increase in *-B D 0inding activity in peripheral

0lood samples of children ith autism. hen the fold increase of *-B in casesnA;5/ as compared ith that of controls nA9%/, there as a significantdifference


32/92

42. utism+ Brain Disorder, or Disorder &hat ffects the BrainO

#linical europsychiatry, 933=

'artha (. 8er0ert '.D., "h.D., 8arvard Hniversity

utism is defined 0ehaviorally, as a syndrome of a0normalities involvinglanguage, social reciprocity and hyperfocus or reduced 0ehavioral flexi0ility. It isclearly heterogeneous, and it can 0e accompanied 0y unusual talents as ell as0y impairments, 0ut its underlying 0iological and genetic 0asis in unknon.

utism has 0een modeled as a 0rain-0ased, strongly genetic disorder, 0utemerging findings and hypotheses support a 0roader model of the condition as agenetically influenced and systemic. &hese include imaging, neuropathology andpsychological evidence of pervasive and not 7ust specific/ 0rain and phenotypic

featuresF postnatal evolution and chronic persistence of 0rain, 0ehavior andtissue changes e.g. inflammation/ and physical illness symptomatology e.g.gastrointestinal, immune, recurrent infection/F overlap ith other disordersF andreports of rate increases and improvement or recovery that support a role formodulation of the condition 0y environmental factors e.g. exacer0ation ortriggering 0y toxins, infectious agents, or others stressors, or improvement 0ytreatment/. 'odeling autism more 0roadly encompasses previous ork, 0ut alsoencourages the expansion of research and treatment to include intermediarydomains of molecular and cellular mechanisms, as ell as chronic tissue,meta0olic and somatic changes previously addressed only to a limited degree.&he heterogeneous 0iologies underlying autism may conceiva0ly converge ontothe autism profile via multiple mechanisms on the one hand and processing and

connectivity a0normalities on the other may illuminate relevant final commonpathays and contri0ute to focusing on the search for treatment targets in this0iologically and etiologically heterogeneous 0ehavioral syndrome.

43. ctivation of 'ethionine Synthase 0y Insulin-like )roth *actor-$ and Dopamine+a &arget for eurodevelopmental &oxins and &himerosal

'ol "sychiatry. 9332 prF%2/+


33/92

exert adverse effects on methylation. e found that insulin-like groth factor-$I)*-$/- and dopamine-stimulated methionine synthase 'S/ activity and folate-dependent methylation of phospholipids in S8-SR=R human neuro0lastomacells, via a "I


34/92

typical infants at $9 months of age. In contrast, infants ith SD ith early onsetof symptoms and no regression displayed feer 7oint attention andcommunicative 0ehaviors at $9 months of age. By 92 months of age, 0oth groupsof toddlers ith SD displayed feer instances of ord use, vocali!ations,declarative pointing, social ga!e, and orienting to name as compared ithtypically developing 92-month-olds.

"arent intervie data suggested that some children ith regression displayeddifficulties in regulatory 0ehavior 0efore the regression occurred.

#onclusion ,his stud- validates the e.istence of earl- autistic regression .

45. Blood evels of 'ercury re (elated to Diagnosis of utism+ (eanalysis of anImportant Data Set

ournal of #hild eurology, Vol. 99, o. $$, $


35/92

utism is a condition characteri!ed 0y impaired cognitive and social skills,associated ith compromised immune function. &he incidence is alarmingly onthe rise, and environmental factors are increasingly suspected to play a role. &hispaper investigates ord fre6uency patterns in the H.S. #D# Vaccine dverseEvents (eporting System VE(S/ data0ase. 1ur results provide strongevidence supporting a link 0eteen autism and the aluminum in vaccines.

literature revie shoing toxicity of aluminum in human physiology offers furthersupport. 'entions of autism in VE(S increased steadily at the end of the lastcentury, during a period hen mercury as 0eing phased out, hile aluminumad7uvant 0urden as 0eing increased. Hsing standard log-likelihood ratiotechni6ues, e identify several signs and symptoms that are significantly moreprevalent in vaccine reports after 9333, including cellulitis, sei!ure, depression,fatigue, pain and death, hich are also significantly associated ith aluminum-containing vaccines. We propose that children with the autism diagnosis areespeciall- vulnerale to to.ic metals such as aluminum and mercur- due toinsufficient serum sulfate and glutathione" A strong correlation etweenautism and the 55R 5easles$ 5umps$ Ruella+ vaccine is also oserved$which ma- e partiall- e.plained via an increased sensitivit- to

acetaminophen administered to control fever"

47. )lutathione-related factors and oxidative stress in autism, a revie.

#urr 'ed #hem. 93$9F$%9


36/92

48. Developmental (egression and 'itochondrial Dysfunction in a #hild ith utism

#hild eurol. 933; *e0F9$9/+$53-9.

on S. "oling, 'D, "hD, Department of eurology and eurosurgeryohns 8opkins 8ospital

0stract utistic spectrum disorders can 0e associated ith mitochondrial dysfunction. epresent a singleton case of developmental regression and oxidativephosphorylation disorder in a $%-month-old girl. Su0tle a0normalities in theserum creatine kinase level, aspartate aminotransferase, and serum 0icar0onateled us to perform a muscle 0iopsy, hich shoed type I myofi0er atrophy,increased lipid content, and reduced cytochrome c oxidase activity. &here eremarked reductions in en!ymatic activities for complex I and III. #omplex IVcytochrome c oxidase/ activity as near the => confidence level. &o determine

the fre6uency of routine la0oratory a0normalities in similar patients, eperformed a retrospective study including $=% patients ith autism Diagnosticand Statistical 'anual of 'ental Disorders-IV and #hildhood utism (atingScale/ not previously diagnosed ith meta0olic disorders and %2 age-matchedcontrols ith other neurologic disorders. spartate aminotransferase aselevated in of patients ith autism compared ith $=> of controls "Q.333$/. &he serum creatine kinase level also as a0normally elevated in 9925>/ of 25 patients ith autism. &hese data suggest that further meta0olicevaluation is indicated in autistic patients and that defects of oxidativephosphorylation might 0e prevalent.

Excerpt+ PChildren who have mitochondrial*related+ d-sfunctional cellular

energ- metaolism might e more prone to undergo autistic regressionetween 1) and 3 months of age if the- also have infections orimmuni8ations at the same time.

49. 1xidative Stress in utism+ Elevated #ere0ellar higher.

0stractIt has 0een suggested that oxidative stress andGor mercury compounds play an

http://jcn.sagepub.com/cgi/content/abstract/21/2/170http://www.scipub.org/fulltext/ajbb/ajbb4273-84.pdfhttp://jcn.sagepub.com/cgi/content/abstract/21/2/170http://www.scipub.org/fulltext/ajbb/ajbb4273-84.pdf


37/92

important role in the pathophysiology of autism. &his study compared for the firsttime the cere0ellar levels of the oxidative stress marker


38/92

a0normalities such as eak central coherence, impaired complex processing,and underconnectivity/, hich are argued to underlie the specific o0serva0le0ehavioral features of autism. &his convergence of findings and models suggeststhat a systems- and chronic disease-0ased reformulation of function andpathophysiology in autism needs to 0e considered, and it opens the possi0ility for ne treatment targets..

Excerpt+ P7.idative stress$ rain inflammation$ and microgliosis have eenmuch documented in association with to.ic e.posures including variousheav- metals"""the awareness that the rain as well as medical conditionsof children with autism ma- e conditioned - chronic iomedicalanormalities such as inflammation opens the possiilit- that meaningfuliomedical interventions ma- e possile well past the window of ma.imalneuroplasticit- in earl- childhood ecause the asis for assuming that alldeficits can e attriuted to fi.ed earl- developmental alterations in neuralarchitecture has now een undermined.P

51. Evidence of &oxicity, 1xidative Stress, and euronal Insult in utism

&oxicol Environ 8ealth B #rit (ev. 933; ov-DecF%;/+2:=-%%.

Lern L, ones '.

Department of "sychiatry, Hniversity of &exas Southestern 'edical #enter atDallas, Dallas, &exas

0stract ccording to the utism Society of merica, autism is no considered to 0e an

epidemic. &he increase in the rate of autism revealed 0y epidemiological studiesand government reports implicates the importance of external or environmentalfactors that may 0e changing. &his article discusses the evidence for the casethat some children ith autism may 0ecome autistic from neuronal cell death or0rain damage sometime after 0irth as result of insultF and addresses thehypotheses that toxicity and oxidative stress may 0e a cause of neuronal insult inautism. &he article first descri0es the "urkin7e cell loss found in autism, "urkin7ecell physiology and vulnera0ility, and the evidence for postnatal cell loss. Second,the article descri0es the increased 0rain volume in autism and ho it may 0erelated to the "urkin7e cell loss. &hird, the evidence for toxicity and oxidativestress is covered and the possi0le involvement of glutathione is discussed.*inally, the article discusses hat may 0e happening over the course of

development and the multiple factors that may interplay and make these childrenmore vulnera0le to toxicity, oxidative stress, and neuronal insult.

52. 1xidative Stress in utism

"athophysiology. 933; ugF$


39/92

#hauhan , #hauhan V.

RS Institute for Basic (esearch in Developmental Disa0ilities, $3=3 *orest 8ill(oad, Staten Island, R

0stract utism is a severe developmental disorder ith poorly understood etiology.1xidative stress in autism has 0een studied at the mem0rane level and also 0ymeasuring products of lipid peroxidation, detoxifying agents such asglutathione/, and antioxidants involved in the defense system against reactiveoxygen species (1S/. ipid peroxidation markers are elevated in autism,indicating that oxidative stress is increased in this disease. evels of ma7orantioxidant serum proteins, namely transferrin iron-0inding protein/ andceruloplasmin copper-0inding protein/, are decreased in children ith autism.&here is a positive correlation 0eteen reduced levels of these proteins and lossof previously ac6uired language skills in children ith autism. &he alterations inceruloplasmin 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 "E/ aredecreased, and phosphatidylserine "S/ levels are increased in the erythrocytemem0rane of children ith autism as compared to their unaffected si0lings.Several studies have suggested alterations in the activities of antioxidanten!ymes such as superoxide dismutase, glutathione peroxidase, and catalase inautism. dditionally, altered glutathione levels and homocysteineGmethioninemeta0olism, increased inflammation, excitotoxicity, as ell as mitochondrial andimmune 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 maycontri0ute to the development of this disease. mechanism linking oxidative

stress ith mem0rane lipid a0normalities, inflammation, a0errant immuneresponse, impaired energy meta0olism and excitotoxicity, leading to clinicalsymptoms and pathogenesis of autism is proposed.

Excerpt+ Ppon completion of this article$ participants should e ale to: 1"e aware of laorator- and clinical evidence of greater o.idative stress inautism" 2" nderstand how gut$ rain$ nutritional$ and to.ic status in autismare consistent with greater o.idative stress" 3" 4escrie how anti*o.idantnutrients are used in the contemporar- treatment of autism"P

53. &himerosal eurotoxicity is ssociated ith )lutathione Depletion+ "rotectionith )lutathione "recursors

eurotoxicology. 933= anF9;$/+$-:.

ames S, Slikker


40/92

0stract&himerosol is an antiseptic containing 2%.=> ethyl mercury that has 0een usedfor years as a preservative in many infant vaccines and in flu vaccines.Environmental methyl mercury has 0een shon to 0e highly neurotoxic,especially to the developing 0rain. Because mercury has a high affinity for thiol

sulfhydryl -S8// groups, the thiol-containing antioxidant, glutathione )S8/,provides the ma7or intracellular defense against mercury-induced neurotoxicity.#ultured neuro0lastoma cells ere found to have loer levels of )S8 andincreased sensitivity to thimerosol toxicity compared to glio0lastoma cells thathave higher 0asal levels of intracellular )S8. ,himerosal*induced c-toto.icit-was associated with depletion of intracellular =69 in oth cell lines" "retreatment ith $33 micro' glutathione ethyl ester or -acetylcysteine #/,0ut not methionine, resulted in a significant increase in intracellular )S8 in 0othcell types. *urther, pretreatment of the cells ith glutathione ethyl ester or #prevented cytotoxicity ith exposure to $= micro' &himerosal. lthough&himerosal has 0een recently removed from most children4s vaccines, it is stillpresent in flu vaccines given to pregnant omen, the elderly, and to children in

developing countries. &he potential protective effect of )S8 or # againstmercury toxicity arrants further research as possi0le ad7unct therapy toindividuals still receiving &himerosal-containing vaccinations.

54. &oxic metals and oxidative stress part I+ mechanisms involved in metal-inducedoxidative damage.

#urr &op 'ed #hem. 933$ DecF$;/+=9%-


41/92

o.idative stress in cells can e partiall- responsile for the to.ic effects ofheav- metals" 6everal studies are underwa- to determine the effect ofantio.idant supplementation following heav- metal e.posure" 4ata suggestthat antio.idants ma- pla- an important role in aating some ha8ards ofheav- metals" In order to prove the importance of using antioxidants in heavymetal poisoning, pertinent 0iochemical mechanisms for metal-induced oxidative

stress should 0e revieed.

55. luminum ad7uvant linked to gulf ar illness induces motor neuron death in mice

euromolecular 'ed. 9335F%$/+:/. Significant cognitive deficits in ater-ma!e learning ere o0servedin the com0ined aluminum and s6ualene group 2.< errors per trial/ comparedith the controls 3.9 errors per trial/ after 93 k. poptotic neurons ereidentified in aluminum-in7ected animals that shoed significantly increasedactivated caspase-< la0eling in lum0ar spinal cord 9==>/ and primary motor

cortex $%9>/ compared ith the controls. luminum-treated groups alsoshoed significant motor neuron loss / and increased num0ers ofastrocytes / in the lum0ar spinal cord. &he findings suggest a possi0le rolefor the aluminum ad7uvant in some neurological features associated ith )Iand possi0ly an additional role for the com0ination of ad7uvants.

http://www.ncbi.nlm.nih.gov/pubmed/17114826http://www.ncbi.nlm.nih.gov/pubmed/17114826


42/92

56. Enrichment of Elevated "lasma *9t-Isoprostane evels in Individuals ith utismho re Stratified 0y "resence of )astrointestinal Dysfunction

"oS 1E :5/+ e;:222.

)orrindo ", ane #, ee EB, 'caughlin B, evitt " uly


43/92

0stract(eported rates of autism have increased sharply in the Hnited States and theHnited Lingdom. 1ne possi0le factor underlying these increases is increasedexposure to mercury through thimerosal-containing vaccines, 0ut vaccineexposures need to 0e evaluated in the context of cumulative exposures duringgestation and early infancy. Differential rates of postnatal mercury elimination

may explain hy similar gestational and infant exposures produce varia0leneurological effects. *irst 0a0y haircut samples ere o0tained from %2 childrendiagnosed ith autism using Diagnostic and Statistical 'anual of 'entalDisorders, 2th edition DS' IV/ criteria and 2= age- and gender-matchedcontrols. Information on diet, dental amalgam fillings, vaccine history, (ho Dimmunoglo0ulin administration, and autism symptom severity as collectedthrough a maternal survey 6uestionnaire and clinical o0servation. 8air mercurylevels in the autistic group ere 3.25 ppm versus


44/92

ho presented to the )enetic #enters of merica for a geneticGdevelopmentalevaluation are discussed. Eight of nine patients one patient as found to havean SD due to (ett4s syndrome/ a/ had regressive SDsF 0/ had elevated levelsof androgensF c/ excreted significant amounts of mercury post chelationchallengeF d/ had 0iochemical evidence of decreased function in theirglutathione pathaysF e/ had no knon significant mercury exposure except

from &himerosal-containing vaccinesG(hoD/-immune glo0ulin preparationsF andf/ had alternate causes for their regressive SDs ruled out. &here as asignificant dose-response relationship 0eteen the severity of the regressive

SDs o0served and the total mercury dose children received from &himerosal-containing vaccinesG(ho D/-immune glo0ulin preparations. Based upondifferential diagnoses, : of % patients examined ere exposed to significantmercury from &himerosal-containing 0iologicGvaccine preparations during theirfetalGinfant developmental periods, and su0se6uently, 0eteen $9 and 92 mo ofage, these previousl- normall- developing children suffered mercur- to.icencephalopathies that manifested with clinical s-mptoms consistent withregressive A64s" @vidence for mercur- into.ication should e consideredin the differential diagnosis as contriuting to some regressive A64s .

59. &he #hanging "revalence of utism In #alifornia

ournal of utism and Developmental Disorders, pril 933<'ark Blaxill, 'B

&his study helps to refute the supposition made 0y some researchers thatautism4s epidemic may only 0e due to Pdiagnostic su0stitutionP.

Excerpt+ P,he- have suggested that diagnostic sustitution accounts foran apparent increase in the incidence of autism in California that is notreal" ,his h-pothesi8ed sustitution is not supported - proper anddetailed anal-ses of the California data.P

60. 'itochondrial Energy-Deficient Endophenotype in utism

merican ournal of Biochemistry and Biotechnology 2 9/+ $%:-935, 933:

. ay )argus and *ai6a Imtia!

Department of "hysiology and Biophysics and Department of "ediatrics, Sectionof 8uman )enetics, School of 'edicine, Hniversity of #alifornia, Irvine, ra0ianDiagnostics a0oratory, Ling *aisal Specialist 8ospital and (esearch #entre

0stract+ hile evidence points to a multigenic etiology of most autism, thepathophysiology of the disorder has yet to 0e defined and the underlying genesand 0iochemical pathays they su0serve remain unknon. utism is consideredto 0e influenced 0y a com0ination of various genetic, environmental andimmunological factorsF more recently, evidence has suggested that increased

http://link.springer.com/article/10.1023%2FA%3A1022912115365?LI=true#page-1http://www.scipub.org/fulltext/ajbb/ajbb42198-207.pdfhttp://link.springer.com/article/10.1023%2FA%3A1022912115365?LI=true#page-1http://www.scipub.org/fulltext/ajbb/ajbb42198-207.pdf


45/92

vulnera0ility to oxidative stress may 0e involved in the etiology of thismultifactorial disorder.

*urthermore, recent studies have pointed to a su0set of autism associated iththe 0iochemical endophenotype of mitochondrial energy deficiency, identified asa su0tle impairment in fat and car0ohydrate oxidation. &his phenotype is similar,

0ut more su0tle than those seen in classic mitochondrial defects. In some casesthe 0eginnings of the genetic underpinnings of these mitochondrial defects areemerging, such as mild mitochondrial dysfunction and secondary carnitinedeficiency o0served in the su0set of autistic patients ith an inverted duplicationof chromosome $=6$$-6$


46/92

cause persistent activation of the innate immune system leading to more (1Sproduction. Such a mechanism ould self-sustain and possi0ly progressivelyorsen. &he mitochondrial dysfunction and altered redox signal transductionpathays found in autism ould conspire to activate 0oth astroglia and microglia.&hese activated cells can then initiate a 0road-spectrum proinflammatory generesponse. Beyond the direct effects of (1S on neuronal function, receptors on

neurons that 0ind the inflammatory mediators may serve to inhi0it neuronalsignaling to protect them from excitotoxic damage during variouspathologic insults e.g., infection/. n autism$ over*8ealous neuroinflammator-responses could not onl- influence neural developmental processes$ utma- more significantl- impair neural signaling involved in cognition in anongoing fashion" ,his model makes specific predictions in patients andexperimental animal models and suggests a num0er of targets sites ofintervention. 1ur model of potentially reversi0le pathophysiological mechanismsin autism motivates our hope that effective therapies may soon appear on thehori!on.

62. 8eavy-'etal &oxicityith Emphasis on 'ercury

ohn eustadt, D, and Steve "iec!enik, 'D, "hD

(esearch (evie

#onclusion+ 'etals are u0i6uitous in our environment, and exposure to them isinevita0le. 8oever, not all people accumulate toxic levels of metals or exhi0itsymptoms of metal toxicity, suggesting that genetics play a role in their potentialto damage health. 5etal to.icit- creates multis-stem d-sfunction$ whichappears to e mediated primaril- through mitochondrial damage fromglutathione depletion"

ccurate screening can increase the likelihood that patients ith potential metaltoxicity are identified. &he most accurate screening method for assessingchronic-metals exposure and metals load in the 0ody is a provoked urine test.

63. Evidence of 'itochondrial Dysfunction in utism and Implications for &reatment

merican ournal of Biochemistry and Biotechnology 2 9/+ 93:-9$5, 933:

Daniel . (ossignol, . effrey Bradstreet, International #hild Development(esource #enter,

0stract#lassical mitochondrial diseases occur in a su0set of individuals ith autism andare usually caused 0y genetic anomalies or mitochondrial respiratory pathaydeficits. 8oever, in many cases of autism, there is evidence of mitochondrialdysfunction 'tD/ ithout the classic features associated ith mitochondrial

http://montanaim.com/pubs/Heavy_Metals_Article.pdfhttp://www.icdrc.org/documents/Mitoandautism2008.pdfhttp://montanaim.com/pubs/Heavy_Metals_Article.pdfhttp://www.icdrc.org/documents/Mitoandautism2008.pdf


47/92

disease. 'tD appears to 0e more common in autism and presents ith lesssevere signs and symptoms. It is not associated ith discerna0le mitochondrialpathology in muscle 0iopsy specimens despite o07ective evidence of loeredmitochondrial functioning. @.posure to environmental to.ins is the likel-etiolog- for 5t4 in autism" ,his d-sfunction then contriutes to a numerof diagnostic s-mptoms and comoridities oserved in autism including:

cognitive impairment$ language deficits$ anormal energ- metaolism$chronic gastrointestinal prolems$ anormalities in fatt- acid o.idation$and increased o.idative stress" 5t4 and o.idative stress ma- also e.plainthe high male to female ratio found in autism due to increased malevulnerailit- to these d-sfunctions"

Biomarkers for mitochondrial dysfunction have 0een identified, 0ut seem idelyunder-utili!ed despite availa0le therapeutic interventions. utritionalsupplementation to decrease oxidative stress along ith factors to improvereduced glutathione, as ell as hyper0aric oxygen therapy 8B1&/ representsupported and rationale approaches. &he underlying pathophysiology andautistic symptoms of affected individuals ould 0e expected to either improve or

cease orsening once effective treatment for 'tD is implemented.

64. "roximity to point sources of environmental mercury release as a predictor ofautism prevalence

8ealth "lace, 933:

(aymond *. "almer, Stephen Blanchard, (o0ert oodHniversity of &exas 8ealth Science #enter, San ntonio Department of *amilyand #ommunity 'edicine, 1ur ady of the ake Hniversity, San ntonio &exas,#hair, Department of Sociology

&his study should 0e vieed as hypothesis-generating - a first step in examiningthe potential role of environmental mercury and childhood developmentaldisorders. othing is knon a0out specific exposure routes, dosage, timing, andindividual suscepti0ility. We suspect that persistent low*dose e.posures tovarious environmental to.icants$ including mercur-$ that occur duringcritical windows of neural development among geneticall- susceptilechildren with a diminished capacit- for metaoli8ing accumulatedto.icants+ ma- increase the risk for developmental disorders such asautism" Successfully identifying the specific com0ination of environmentalexposures and genetic suscepti0ilities can inform the development of targetedprevention intervention strategies.

65. Epidemiology of autism spectrum disorder in "ortugal+ prevalence, clinicalcharacteri!ation, and medical conditions

http://www.science-direct.com/science?_ob=PublicationURL&_tockey=%23TOC%236057%239999%23999999999%2399999%23FLA%23&_cdi=6057&_pubType=J&view=c&_auth=y&_acct=C000063557&_version=1&_urlVersion=0&_userid=4861547&md5=d7e7aa3ca8459defec32118466c4ce6dhttp://www.science-direct.com/science?_ob=PublicationURL&_tockey=%23TOC%236057%239999%23999999999%2399999%23FLA%23&_cdi=6057&_pubType=J&view=c&_auth=y&_acct=C000063557&_version=1&_urlVersion=0&_userid=4861547&md5=d7e7aa3ca8459defec32118466c4ce6dhttp://adventuresinautism.com/images/VivaPortugal.pdfhttp://adventuresinautism.com/images/VivaPortugal.pdfhttp://www.science-direct.com/science?_ob=PublicationURL&_tockey=%23TOC%236057%239999%23999999999%2399999%23FLA%23&_cdi=6057&_pubType=J&view=c&_auth=y&_acct=C000063557&_version=1&_urlVersion=0&_userid=4861547&md5=d7e7aa3ca8459defec32118466c4ce6dhttp://www.science-direct.com/science?_ob=PublicationURL&_tockey=%23TOC%236057%239999%23999999999%2399999%23FLA%23&_cdi=6057&_pubType=J&view=c&_auth=y&_acct=C000063557&_version=1&_urlVersion=0&_userid=4861547&md5=d7e7aa3ca8459defec32118466c4ce6dhttp://adventuresinautism.com/images/VivaPortugal.pdfhttp://adventuresinautism.com/images/VivaPortugal.pdf


48/92

Developmental 'edicine #hild eurology, 9335

)uiomar 1liveira 'D "hD, #entro de Desenvolvimento da #riana, 8ospital"editrico de #oim0raF ssunjo tade BSc, Direcjo (egional de Educajodo #entro #oim0raF

#arla 'ar6ues 'Sc, #entro de Desenvolvimento da #riana, 8ospital "editricode #oim0raF &eresa S 'iguel BSc, Direcjo (egional de Educajo do #entro,#oim0raF

na 'argarida #outinho BSc, Instituto )ul0enkian de #incia, 1eirasF usa'ota-Vieira "hD, Hnidade de )en]tica e "atologia moleculares, 8ospital doDivino Esprito Santo, "onta Delgada, oresF Esmeralda )onalves "hDFa!ar] 'endes opes "hD, *aculdade de #incias e &ecnologia, Hniversidadede #oim0raF Vitor (odrigues 'D "hDF 8enri6ue #armona da 'ota 'D "hD,*aculdade de 'edicina, Hniversidade de #oim0ra, #oim0raF strid 'ouraVicente "hD, Instituto )ul0enkian de #incia, 1eiras, "ortugal.[#orrespondence to first author at 8ospital "editrico de #oim0ra, v BissayaBarreto,


49/92

caused apoptosis detected 0y 8oechst


50/92

68. "ossi0le Immunological Disorders in utism+ #oncomitant utoimmunity andImmune &olerance

&he Egyptian ournal of Immunology, 933;

'aha I. Sh. Laashti, 1mnia (. min adia ). (oehy

'icro0iology Department, *aculty of 'edicine *or )irls/, l !har Hniversity,#airo, Egypt, "sychiatry Department, *aculty of 'edicine, #airo Hniversity,#airo, Egypt and Serology a0 Ling *ahad )eneral 8ospital, eddah, L.S..

0stract+ utism is a pervasive developmental disorder that affect children earlyin their life. Immunological disorders is one of several contri0uting factors thathave 0een suggested to cause autism. &hirty autistic children aged and ;.5> positivity inthe control group. Surprisingly, circulating anti-measles, anti-mumps and anti-ru0ella Ig) ere positive in only =3>, 5


51/92

of Lentucky, exington, LR E. (. hite , #hemistry, Hniversity of Lentucky,exington, LR . akefield , &houghtful 8ouse #enter for #hildren, ustin, &

0stractBackground+ 'aca6ues are commonly used in pre-clinical vaccine safety testing,0ut the com0ined childhood vaccine regimen, rather than individual vaccines, has

not 0een studied. #hildhood vaccines are a possi0le causal factor in autism, anda0normal 0ehaviors and anomalous amygdala groth are potentially inter-relatedfeatures of this condition.

107ectives+ &he o07ective of this study as to compare early infant cognition and0ehavior ith amygdala si!e and opioid 0inding in rhesus maca6ues receivingthe recommended childhood vaccines $%%2-$%%%/, the ma7ority of hichcontained the 0actericidal preservative ethylmercurithiosalicylic acid thimerosal/.

'ethods+ 'aca6ues ere administered the recommended infant vaccines,ad7usted for age and thimerosal dose exposedF A$


52/92

&he )eorge ashington Hniversity School of "u0lic 8ealth and 8ealth Services,Department of Epidemiology and Biostatistics, Hnited States.

0stract&he study evaluated possi0le associations 0eteen neurodevelopmentaldisorders Ds/ and exposure to mercury 8g/ from &himerosal-containing

vaccines Vs/ 0y examining the automated Vaccine Safety Datalink VSD/. total of 95:,;92 su07ects ere identified in 0irth cohorts from $%%3-$%%; that hadreceived their first oral polio vaccination 0y < months of age in the VSD. &he 0irthcohort prevalence rate of medically diagnosed International #lassification ofDisease, %th revision I#D-%/ specific Ds and control outcomes erecalculated. Exposures to 8g from Vs ere calculated 0y 0irth cohort forspecific exposure indos from 0irth-5 months and 0irth-$< months of age."oisson regression analysis as used to model the association 0eteen theprevalence of outcomes and 8g doses from Vs. Consistent significantl-increased rate ratios were oserved for autism$ autism spectrum disorders$tics$ attention deficit disorder$ and emotional disturances with 9ge.posure from ,CVs" By contrast, none of the control outcomes had

significantly increased rate ratios ith 8g exposure from Vs. (outinechildhood vaccination should 0e continued to help reduce the mor0idity andmortality associated ith infectious diseases, 0ut efforts should 0e undertaken toremove 8g from vaccines. dditional studies should 0e conducted to furtherevaluate the relationship 0eteen 8g exposure and Ds.

71. )lutathione, oxidative stress and neurodegeneration

Schul! B, indenau , Seyfried , Dichgans .eurodegeneration a0oratory, Department of eurology, Hniversity of &0ingen,)ermany.

Eur Biochem. 9333 ugF9;5$;/+2%32-$$.

0stract,here is significant evidence that the pathogenesis of severalneurodegenerative diseases$ including Darkinsons disease$ Al8heimersdisease$ Friedreichs ata.ia and am-otrophic lateral sclerosis$ ma- involvethe generation of reactive o.-gen species and mitochondriald-sfunction" 8ere, e revie the evidence for a distur0ance of glutathionehomeostasis that may either lead to or result from oxidative stress inneurodegenerative disorders. )lutathione is an important intracellular antioxidantthat protects against a variety of different antioxidant species. n important rolefor glutathione as proposed for the pathogenesis of "arkinson4s disease,0ecause a decrease in total glutathione concentrations in the su0stantia nigrahas 0een o0served in preclinical stages, at a time at hich other 0iochemicalchanges are not yet detecta0le. Because glutathione does not cross the 0lood-0rain 0arrier other treatment options to increase 0rain concentrations ofglutathione including glutathione analogs, mimetics or precursors are discussed.



53/92

72. 8epatitis B triple series vaccine and developmental disa0ility in HS children aged$-% years

#arolyn )allagher aF 'elody )oodman, )raduate "rogram in "u0lic 8ealth,Stony Brook Hniversity 'edical #enter, 8ealth Sciences #enter, e Rork, HS

ournal &oxicological Environmental #hemistry, Volume %3, Issue = Septem0er 933: , pages %%5 - $33:

0stract&his study investigated the association 0eteen vaccination ith the 8epatitis Btriple series vaccine prior to 9333 and developmental disa0ility in children aged$N% years n A $:92/, proxied 0y parental report that their child receives earlyintervention or special education services EIS/. ational 8ealth and utritionExamination Survey $%%%N9333 data ere analy!ed and ad7usted for surveydesign 0y &aylor ineari!ation using SS version %.$ softare, ith SS calla0leSHD version %.3.$. &he odds of receiving EIS ere approximately nine timesas great for vaccinated 0oys n A 2;/ as for unvaccinated 0oys n A 5/, afterad7ustment for confounders. ,his stud- found statisticall- significantevidence to suggest that o-s in nited 6tates who were vaccinated withthe triple series 9epatitis vaccine$ during the time period in whichvaccines were manufactured with thimerosal$ were more susceptile todevelopmental disailit- than were unvaccinated o-s.

73. Induction of metallothionein in mouse cere0ellum and cere0rum ith lo-dosethimerosal in7ection.

'inami &, 'iyata E, Sakamoto R, Rama!aki 8, Ichida S., Department of ifeSciences, School of Science Engineering, Linki Hniversity,


54/92

expression in the cere0ellum as three times higher than that in the cere0rumafter the in7ection of $9 microgGkg thimerosal. '&-9 m( as not expresseduntil 92 h in 0oth organs. '&-< m( as expressed in the cere0ellum from ; to$= h after the in7ection, 0ut not in the cere0rum until 92 h. '&-$ and '&-<m(s ere expressed in the cere0ellum in a dose-dependent manner.*urthermore, '&-$ protein as detected from ; to 59 h in the cere0ellum after $9

microgGkg of thimerosal as in7ected and peaked at $3 h. '&-9 as detected inthe cere0ellum only at $3 h. In the cere0rum, little '&-$ protein as detected at$3 and 92 h, and there ere no peaks of '&-9 protein in the cere0rum. Inconclusion, '&-$ and '&-< m(s 0ut not '&-9 m( are easily expressed inthe cere0ellum rather than in the cere0rum 0y the in7ection of lo-dosethimerosal. It is thought that the cere0ellum is a sensitive organ againstthimerosal. As a result of the present findings$ in comination with the rainpatholog- oserved in patients diagnosed with autism$ the present stud-helps to support the possile iological plausiilit- for how low*dosee.posure to mercur- from thimerosal*containing vaccines ma- eassociated with autism"

74. 'ercury induces inflammatory mediator release from human mast cells

Duraisamy Lempura7, Shahr!ad sadi, Bodi Khang, krivi 'anola, ennifer8ogan, Erika "eterson, &heoharis # &heoharides

ournal of euroinflammation 93$3, 5+93 doi+$3.$$:;G$529-93%2-5-93

0stractBackground+ 'ercury is knon to 0e neurotoxic, 0ut its effects on the immunesystem are less ell knon. 'ast cells are involved in allergic reactions, 0ut alsoin innate and ac6uired immunity, as ell as in inflammation. 'any patients ith

utism Spectrum Disorders SD/ have allergic symptomsF moreover, theprevalence of SD in patients ith mastocytosis, characteri!ed 0y numeroushyperactive mast cells in most tissues, is $3-fold higher than the generalpopulation suggesting mast cell involvement. e, therefore, investigated theeffect of mercuric chloride 8g#l9/ on human mast cell activation.

'ethods+ 8uman leukemic cultured D9 mast cells and normal human um0ilicalcord 0loodderived cultured mast cells h#B'#s/ ere stimulated 0y 8g#l9 3.$-$3 Z'/ for either $3 min for 0eta-hexosaminidase release or 92 hr for measuringvascular endothelial groth factor VE)*/ and I-; release 0y EIS.

(esults+ 8g#l9 induced a 9-fold increase in -hexosaminidase release, and alsosignificant VE)* release at 3.$ and $ Z'


55/92

3.$ Z'/ compared to untreated cells $


56/92

eurotoxicology. 933; SepF95=/+;:=-%9. Epu0 933; un $;.

alker S, Segal , schner '.

Department of "hysiology and "harmacology, ake *orest Hniversity School of

'edicine, inston-Salem, # 95$=;, HS. salkerJfu0mc.edu 0stract

0stract&here are reports suggesting that some autistic children are una0le to mount anade6uate response folloing exposure to environmental toxins. &his potentialdeficit, coupled ith the similarity in clinical presentations of autism and someheavy metal toxicities, has led to the suggestion that heavy metal poisoningmight play a role in the etiology of autism in uni6uely suscepti0le individuals.&himerosal, an anti-micro0ial preservative previously added routinely tochildhood multi-dose vaccines, is composed of 2%.;> ethyl mercury. Based onthe 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 0ea 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 aheavy metal challenge. &o investigate this hypothesis, cultured lymphocyteso0tained from the utism )enetic (esource Exchange, )(E/ from autisticchildren and non-autistic si0lings ere challenged ith either $3 micro' ethylmercury, $=3 micro' !inc, or fresh media control/. *olloing the challenge, total( as extracted and used to 6uery Phole genomeP D microarrays.#ultured lymphocytes challenged ith !inc responded ith an impressive up-regulation of '& transcripts at least nine different '&s ere over-expressed/ while cells challenged with thimerosal responded - up*

regulating numerous heat shock protein transcripts$ ut not 5,s" Althoughthere were no apparent differences etween autistic and non*autisticsiling responses in this ver- small sampling group$ the differences ine.pression profiles etween those cells treated with 8inc versus thimerosalwere dramatic" Determining cellular response, at the level of gene expression,has important implications for the understanding and treatment of conditions thatresult from exposure to neurotoxic compounds.

77. Sorting out the spinning of autism+ heavy metals and the 6uestion of incidence

cta euro0iol Exp 93$3, 53+ $;=N$5;

'ary #atherine DeSoto[ and (o0ert &. 8itlan, Department of "sychology,Hniversity of orthern Ioa, #edar *alls, Ioa, HS

&he reasons for the rise in autism prevalence are a su07ect of heatedprofessional de0ate. *eaturing a critical appraisal of some research used to

http://www.autismresourceconnection.com/documents/Sorting%20out%20the%20spinning%20of%20autism.pdfhttp://www.autismresourceconnection.com/documents/Sorting%20out%20the%20spinning%20of%20autism.pdf


57/92

6uestion hether there is a rise in cases and if rising levels of autism are relatedto environmentalexposure to toxins Soden et al. 9335, &hompson et al. 9335, Bar0aresi et al.933%/ e aim to evaluate the actual state of scientific knoledge. In addition, esurveyed 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 importanthealth topics today. e argue that scientific research does not support re7ectingthe link 0eteen the neurodevelopmental disorder of autism and toxic exposures.

78. Hrinary "orphyrin Excretion in eurotypical and utistic #hildren

Environ 8ealth "erspect. 93$3 1ctF$$:$3/+$2=3-5. Epu0 93$3 un 92.

oods S, rmel SE, *ulton DI, llen , essels L, Simmonds ",)ranpeesheh D, 'umper E, Bradstreet , Echeverria D, 8eyer , (ooney ".,Department of Environmental and 1ccupational 8ealth Sciences, Hniversity ofashington

0stractB#L)(1HD+ Increased urinary concentrations of pentacar0oxyl-, precopro-and copro-porphyrins have 0een associated ith prolonged mercury 8g/exposure in adults, and compara0le increases have 0een attri0uted to 8gexposure in children ith autism H/.

1BE#&IVES+ &his study as designed to measure and compare urinaryporphyrin concentrations in neurotypical &/ children and same-age childrenith autism, and to examine the association 0eteen porphyrin levels and past or current 8g exposure in children ith autism.

'E&81DS+ &his exploratory study enrolled 95: children 9-$9 years of age. eevaluated three groups+ H, pervasive developmental disorder-not otherisespecified "DD-1S/, and &. 'othersGcaregivers provided information atenrollment regarding medical, dental, and dietary exposures. Hrine samples fromall children ere ac6uired for analyses of porphyrin, creatinine, and 8g.Differences 0eteen groups for mean porphyrin and 8g levels ere evaluated.ogistic regression analysis as conducted to determine hether porphyrinlevels ere associated ith increased risk of autism.

(ESH&S+ 'ean urinary porphyrin concentrations are naturally high in youngchildren and decline 0y as much as 9.=-fold 0eteen 9 and $9 years of age.Elevated copro- p Q 3.33%/, hexacar0oxyl- p Q 3.3$/ and pentacar0oxyl- p Q3.33$/ porphyrin concentrations ere significantly associated ith H 0ut notith "DD-1S. o differences ere found 0eteen & and H in urinary 8glevels or in past 8g exposure as determined 0y fish consumption, num0er ofdental amalgam fillings, or vaccines received. #1#HSI1S+,hese findingsidentif- disordered porph-rin metaolism as a salient characteristic of



58/92

autism" 8g exposures ere compara0le 0eteen diagnostic groups, and aporphyrin pattern consistent ith that seen in 8g-exposed adults as notapparent.

79. 'itochondrial dysfunction in autism spectrum disorders+ a systematic revie andmeta-analysis

'olecular "sychiatry advance online pu0lication 9= anuary 93$$Fdoi+$3.$3 confidence interval /, much higherthan found in the general population U3.3$>/. &he prevalence of a0normal0iomarker values of mitochondrial dysfunction as high in SD, much higherthan the prevalence of 'D. Variances and mean values of many mitochondrial0iomarkers lactate, pyruvate, carnitine and u0i6uinone/ ere significantlydifferent 0eteen SD and controls. Some markers correlated ith SD severity.euroimaging, in vitro and post-mortem 0rain studies ere consistent ith anelevated prevalence of mitochondrial dysfunction in SD. &aken together, thesefindings suggest children ith SD have a spectrum of mitochondrial dysfunctionof differing severity. Eighteen pu0lications representing a total of $$9 childrenith SD and 'D SDG'D/ ere identified. &he prevalence of developmentalregression =9>/, sei!ures 2$>/, motor delay =$>/, gastrointestinala0normalities 52>/, female gender /, and elevated lactate 5:>/ andpyruvate 2=>/ as significantly higher in SDG'D compared ith the general

SD population. &he prevalence of many of these a0normalities as similar tothe general population of children ith 'D, suggesting that SDG'D represents adistinct su0group of children ith 'D. 'ost SDG'D cases 5%>/ ere notassociated ith genetic a0normalities, raising the possi0ility of secondarymitochondrial dysfunction. &reatment studies for SDG'D ere limited, althoughimprovements ere noted in some studies ith carnitine, co-en!yme X$3 and B-vitamins. 'any studies suffered from limitations, including small sample si!es,referral or pu0lication 0iases, and varia0ility in protocols for selecting children for'D orkup, collecting mitochondrial 0iomarkers and defining 'D. 7verall$ thisevidence supports the notion that mitochondrial d-sfunction is associatedwith A64" dditional studies are needed to further define the role ofmitochondrial dysfunction in SD.

http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2010136a.htmlhttp://www.nature.com/mp/journal/vaop/ncurrent/full/mp2010136a.htmlhttp://www.nature.com/mp/journal/vaop/ncurrent/full/mp2010136a.htmlhttp://www.nature.com/mp/journal/vaop/ncurrent/full/mp2010136a.html


59/92

80. Sensiti!ation effect of thimerosal is mediated in vitro via reactive oxygen speciesand calcium signaling.

&oxicology. 93$3 uly - ugustF952$-


60/92

Increases in the reported prevalence of autism and autistic spectrum disorders inrecent years have fueled concern over possi0le environmental causes. &heauthor revies the availa0le survey literature and finds evidence of largeincreases in prevalence in 0oth the Hnited States and the Hnited Lingdom thatcannot 0e explained 0y changes in diagnostic criteria or improvements in caseascertainment. Incomplete ascertainment of autism cases in young child

populations is the largest source of predicta0le 0ias in prevalence surveysFhoever, this 0ias has, if anything, orked against the detection of an upardtrend in recent surveys. #omparison of autism rates 0y year of 0irth for specificgeographies provides the strongest 0asis for trend assessment. Suchcomparisons sho large recent increases in rates of autism and autisticspectrum disorders in 0oth the H.S. and the H.L. (eported rates of autism in theHnited States increased from Q < per $3,333 children in the $%53s to


61/92

correlate the timing of changes in incidence ith environmental changes. utismcould result from more than one cause, ith different manifestations in differentindividuals that share common symptoms. Documented causes of autism includegenetic mutations andGor deletions, viral infections, and encephalitis folloingvaccination. ,herefore$ autism is the result of genetic defects and/orinflammation of the rain" ,he inflammation could e caused - a defective

placenta$ immature lood*rain arrier$ the immune response of the mother to infection while pregnant$ a premature irth$ encephalitis in the child after irth$ or a to.ic environment"

84. Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants

&he ournal of "ediatrics, Volume $


62/92

/ term-0orn infants completed the '-#8& 6uestionnaire. '"& infants had significantly higher risk of a positive6uestionnaire screen compared ith controls $2.=> vs %.9>F relative risk ?((@$.=:F %=> #I $.$:, 9.$$/. fter follo-up, significantly more '"& infants thancontrols had a true positive screen 9.2> vs 3.=>F (( 2.=9F $.=$, $vs 3.=>F ((


63/92

1BE#&IVE+&o estimate the extent to hich the associations 0eteen early gestational ageand offspring mortality and mor0idity are the result of confounding factors 0yusing a 6uasi-experimental design, the si0ling-comparison approach, and 0ycontrolling for statistical covariates that varied ithin families.DESI), SE&&I), D "(&I#I"&S+

population-0ased cohort study, com0ining Sedish registries to identify allindividuals 0orn in Seden from $%5< to 933:


64/92

"ink disease infantile acrodynia/ as especially prevalent in the first half of the93th century. "rimarily attri0uted to exposure to mercury 8g/ commonly found inteething poders, the condition as developed 0y approximately $ in =33exposed children. &he differential risk factor as identified as an idiosyncraticsensitivity to 8g. utismspectrum disorders SD/ have also 0een postulated to0e produced 0y 8g. nalogous to the pink disease experience, 8g exposure is

idespread yet only a fraction of exposed children develop an SD, suggestingsensitivity to 8g may also 0e present in children ith an SD. &he o07ective ofthis study as to test the hypothesis that individuals ith a knonhypersensitivity to 8g pink disease survivors/ may 0e more likely to havedescendants ith an SD. *ive hundred and tenty-to participants ho hadpreviously 0een diagnosed ith pink disease completed a survey on the healthoutcomes of their descendants. &he prevalence rates of SD and a variety ofother clinical conditions diagnosed in childhood attention deficit hyperactivitydisorder, epilepsy, *ragile syndrome, and Don syndrome/ ere compared toell-esta0lished general population prevalence rates. &he results shoed theprevalence rate of SD among the grandchildren of pink disease survivors $ in99/ to 0e significantly higher than the compara0le general population prevalence

rate $ in $;3/. ,he results support the h-pothesis that 9g sensitivit- ma-e a heritale/genetic risk factor for A64"

88. (isk *actors for utistic (egression+ (esults of an m0ispective #ohort Study.

#hild eurol. 93$9 an


65/92

'el0ye ', 1lsen .

'. 9332 ul 9$F9%9


66/92

90. #ommon variants associated ith general and ''( vaccineNrelated fe0rilesei!ures

B7arke *eenstra, B7Mrn "asternak, *rank )eller, is0eth #arstensen, &ongfeiang, *en 8uang, ennifer Eitson, 'ads V 8ollegaard, 8enrik SvanstrMm,'ogens Vestergaard, David ' 8ougaard, ohn Schoggins, ily Reh an, 'ads

'el0ye nders 8viid

ature )enetics 93$2/ doi+$3.$3


67/92

vaccinations and $:2,


68/92

rapid increase of glutamate overflo. #oadministration of the neurosteroid,dehydroepiandrosterone sulfate D8ESF :3 mgGkgF i.p./ prevented thethimerosal effect on glutamate and aspartateF the steroid alone had no influenceon these amino acids. #oapplication of D8ES ith thimerosal in perfusion fluidalso 0locked the acute action of thimerosal on glutamate. In contrast, D8ESalone reduced overflo of glycine and alanine, somehat potentiating the

thimerosal effect on these amino acids. 6ince e.cessive accumulation ofe.tracellular glutamate is linked with e.citoto.icit-$ our data impl- thatneonatal e.posure to thimerosal*containing vaccines might inducee.citoto.ic rain in?uries$ leading to neurodevelopmental disorders" D8ESmay partially protect against mercurials-induced neurotoxicity.

93. eonatal dministration of &himerosal #auses "ersistent #hanges in 'u 1pioid(eceptors in the (at Brain

eurochem (es. 93$3 ovem0erF


69/92

"ace Environmental a (evie, vol. 9:, no. 9, 93$$

'ary 8olland, ouis #onte, (o0ert Lrako and isa #olin

Executive SummaryIn $%:;, #ongress created the Vaccine In7ury #ompensation "rogram VI#"/

under the ational #hildhood Vaccine In7ury ct $%:; a/. &his "rogram hasoriginal 7urisdiction for childrenTs claims of vaccine in7ury. Because almost allchildren receive multiple vaccinations for daycare and school, it is criticallyimportant that the "rogram provides fundamental fairness, due process andtransparency.

,his empirical investigation$ pulished in a peer*reviewed law ?ournal$e.amines claims that the VCD compensated for vaccine*inducedencephalopath- and sei8ure disorder" ,he VCD has compensatedappro.imatel- 2$& claims of vaccine in?ur- since the inception of theprogram" ,his stud- found )3 cases of acknowledged vaccine*inducedrain damage that include autism$ a disorder that affects speech$ social

communication and ehavior" In 9$ pu0lished cases of the #ourt of *ederal#laims, hich administers the VI#", the #ourt stated that the petitioners hadautism or descri0ed autism unam0iguously. In ;9 remaining cases, the authorsidentified settlement agreements here 8ealth and 8uman Services 88S/compensated children ith vaccine-induced 0rain damage, ho also have autismor an autism spectrum disorder.

"arents reported the existence of autism in telephone intervies and suppliedsupplemental materials including medical diagnoses, school records, andcompleted, standard autism screening 6uestionnaires to verify their reports. In of the cases of vaccine in7ury revieed, there isconfirmation of autism or autism spectrum disorder 0eyond parental report.

,his finding of autism in compensated cases of vaccine in?ur- issignificant" "6" government spokespeople have een asserting novaccine*autism link for more than a decade" ,his finding calls into 0uestionthe decisions of the Court of Federal Claims in the 7mnius AutismDroceeding in 2% and 21 and the statement of 9ealth and 9uman6ervices on its wesite that M996 has never concluded in an- case thatautism was caused - vaccination"N

Hsing pu0licly availa0le information, the investigation shos that the VI#" has0een compensating cases of vaccine-induced 0rain damage associated ithautism for more than tenty years. &his investigation suggests that officials at

88S, the Department of ustice and the #ourt of *ederal #laims may have 0eenaare of this association 0ut failed to pu0licly disclose it.

&he study calls on #ongress to thoroughly investigate the VI#", including amedical investigation of compensated claims of vaccine in7ury. &his investigationcalls on #ongress to get ansers to these critically important unansered6uestions.


70/92

95. Integrating experimental in vitro and in vivo/ neurotoxicity studies of lo-dosethimerosal relevant to vaccines.

eurochem (es. 93$$ unF


71/92

mechanistic investigations of cytotoxicity induced 0y hepatitis B vaccine, and toinvestigate the mechanisms of vaccine-induced cell death. &he mouse liverhepatoma cell line 8epa$-; as treated ith to doses of ad7uvanted aluminiumhydroxide/ hepatitis B vaccine 3.= and $ Zg protein per ml/ and cell integrity asmeasured after 92, 2: and 59 h. 8epatitis B vaccine exposure increased cellapoptosis as detected 0y flo cytometry and &HE assay. Vaccine exposure

as accompanied 0y significant increases in the levels of activated caspase


72/92

toxic outcomes in patients exposed to thimerosal.1ur study is the firstdemonstration that thimerosal can induce the activation of L and "-$ in theSL--S8 neuro0lastoma cell line. e shoed that activation of cun and "-$transcriptional activity folloing thimerosal treatment does not appear to 0einvolved in the induction of apoptosis, as demonstrated ith the studies using thecun dominant negative. *urthermore, e ere a0le to sho that L is an

essential upstream component of this pathay through the use of the Linhi0itor S";33$9=. &his compound as a0le to attenuate activation ofdonstream components of mitochondrial-mediated cell death and su0se6uentlyprotect the cells from apoptosis. &hese results are significant 0ecause identifyingspecific signaling pathays activated in response to thimerosal exposurepresents pharmacological targets for attenuating potential toxicity in patientsexposed to thimerosal-containing products.

98. 'aternal thimerosal exposure results in a0errant cere0ellar oxidative stress,thyroid hormone meta0olism, and motor 0ehavior in rat pupsF sex- and strain-dependent effects.

#ere0ellum. 93$9 unF$$9/+=5=-:;. doi+ $3.$335Gs$9


73/92

99. &he rise in autism and the role of age at diagnosis .

Epidemiology. 933% anF93$/+:2-%3. doi+ $3.$3%5GEDE.303$


74/92

9 Hniversit] "aris Est, *acult] de ']decine, : rue du )]n]ral Sarrail, #r]teil,%23$3, *rance

< Inserm, H'(-S %2=, %$ Boulevard de lT8pital, "aris, 5=3$


75/92

chemoattractant, and a variation in the ##9 gene, e designed mouseexperiments to assess 0iodistri0ution of vaccine-derived aluminum and of alum-particle fluorescent surrogates in7ected in muscle. luminum as detected intissues 0y 'orin stain and particle induced -ray emission/ "IE/ Both =33 nmfluorescent latex 0eads and vaccine alum agglomerates-si!ed nanohy0rids l-(ho/ ere used.

(esults+Intramuscular in7ection of alum-containing vaccine as associated ith theappearance of aluminum deposits in distant organs, such as spleen and 0rainhere they ere still detected one year after in7ection. Both fluorescent materialsin7ected into muscle translocated to draining lymph nodes Ds/ and thereafterere detected associated ith phagocytes in 0lood and spleen. "articles linearlyaccumulated in the 0rain up to the six-month endpointF they ere first found inperivascular #D$$0W cells and then in microglia and other neural cells. Da0lation dramatically reduced the 0iodistri0ution. #ere0ral translocation as noto0served after direct intravenous in7ection, 0ut significantly increased in miceith chronically altered 0lood-0rain-0arrier. ossGgain-of-function experimentsconsistently implicated ##9 in systemic diffusion of l-(ho particles captured 0y

monocyte-lineage cells and in their su0se6uent neurodelivery. Stereotacticparticle in7ection pointed out 0rain retention as a factor of progressive particleaccu

123 research papers supporting the vaccine autism link

Documents