Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Entropy, November 7, 2012

Stephanie Seneff, Robert M. Davidson and Jingjing Liu

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA,  Internal Medicine Group Practice, PhyNet, Inc., Longview, TX 75604, USA

Abstract: Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever.

Hepatitis B Vaccine Causes Mitochondrial Disorders and Cell Death

Apoptosis. 2012 Jan 17. [Epub ahead of print]

Hepatitis B vaccine induces apoptotic death in Hepa1-6 cells.

Hamza H, Cao J, Li X, Li C, Zhu M, Zhao S.

Source

Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China, Heyam68_hamza@yahoo.com.

Abstract

Vaccines can have adverse side-effects, and these are predominantly associated with the inclusion of chemical additives such as aluminum hydroxide adjuvant. The objective of this study was to establish an in vitro model system amenable to mechanistic investigations of cytotoxicity induced by hepatitis B vaccine, and to investigate the mechanisms of vaccine-induced cell death. The mouse liver hepatoma cell line Hepa1-6 was treated with two doses of adjuvanted (aluminium hydroxide) hepatitis B vaccine (0.5 and 1 μg protein per ml) and cell integrity was measured after 24, 48 and 72 h. Hepatitis B vaccine exposure increased cell apoptosis as detected by flow cytometry and TUNEL assay. Vaccine exposure was accompanied by significant increases in the levels of activated caspase 3, a key effector caspase in the apoptosis cascade. Early transcriptional events were detected by qRT-PCR. We report that hepatitis B vaccine exposure resulted in significant upregulation of the key genes encoding caspase 7, caspase 9, Inhibitor caspase-activated DNase (ICAD), Rho-associated coiled-coil containing protein kinase 1 (ROCK-1), and Apoptotic protease activating factor 1 (Apaf-1). Upregulation of cleaved caspase 3,7 were detected by western blot in addition to Apaf-1 and caspase 9 expressions argues that cell death takes place via the intrinsic apoptotic pathway in which release of cytochrome c from the mitochondria triggers the assembly of a caspase activation complex. We conclude that exposure of Hepa1-6 cells to a low dose of adjuvanted hepatitis B vaccine leads to loss of mitochondrial integrity, apoptosis induction, and cell death, apoptosis effect was observed also in C2C12 mouse myoblast cell line after treated with low dose of vaccine (0.3, 0.1, 0.05 μg/ml). In addition In vivo apoptotic effect of hepatitis B vaccine was observed in mouse liver.

Conflicts of Interest in Vaccine Safety Research

Conflicts of Interest in Vaccine Safety Research

Accountability in Research. 19:65-88. 2012

Gayle DeLong, Department of Economics and Finance, Baruch College, New York,
New York, USA

Conflicts of interest (COls) cloud vaccine safety research. Sponsors of research have competing interests that may impede the objective study of vaccine side effects. Vaccine manufacturers, health officials, and medical journals may have financial and bureaucratic reasons for not wanting to acknowledge the risks of vaccines. Conversely, some advocacy groups may have legislative and financial reasons to sponsor research that finds risks in vaccines. Using the vaccine-autism debate as an illustration, this article details the conflicts of interest each of these groups faces, outlines the current state of vaccine safety research, and suggests remedies to address COls. Minimizing COls in vaccine safety research could reduce research bias and restore greater trust in the vaccine program.

Hyperbaric oxygen treatment for inflammatory bowel disease: a systematic review and analysis

Daniel A Rossignol

• Correspondence: Daniel A Rossignol rossignolmd@gmail.com

Medical Gas Research 2012, 2:6 doi:10.1186/2045-9912-2-6

Published: 15 March 2012

Abstract (provisional)

Background

Traditionally, hyperbaric oxygen treatment (HBOT) has been used to treat a limited repertoire of disease, including decompression sickness and healing of problem wounds. However, some investigators have used HBOT to treat inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis.

Methods

Comprehensive searches were conducted in 8 scientific databases through 2011 to identify publications using HBOT in IBD. Human studies and animal models were collated separately.

Results

Thirteen studies of HBOT in Crohn's disease and 6 studies in ulcerative colitis were identified. In all studies, participants had severe disease refractory to standard medical treatments, including corticosteroids, immunomodulators and anti-inflammatory medications. In patients with Crohn's disease, 31/40 (78%) had clinical improvements with HBOT, while all 39 patients with ulcerative colitis improved. One study in Crohn's disease reported a significant decrease in proinflammatory cytokines (IL-1, IL-6 and TNF-alpha) and one study in ulcerative colitis reported a decrease in IL-6 with HBOT. Adverse events were minimal. Twelve publications reported using HBOT in animal models of experimentally-induced IBD, including several studies reporting decreased markers of inflammation or immune dysregulation, including TNF-alpha (3 studies), IL-1beta (2 studies), neopterin (1 study) and myeloperoxidase activity (5 studies). HBOT also decreased oxidative stress markers including malondialdehyde (3 studies) and plasma carbonyl content (2 studies), except for one study that reported increased plasma carbonyl content. Several studies reported HBOT lowered nitric oxide (3 studies) and nitric oxide synthase (3 studies) and one study reported a decrease in prostaglandin E2 levels. Four animal studies reported decreased edema or colonic tissue weight with HBOT, and 8 studies reported microscopic improvements on histopathological examination. Although most publications reported improvements with HBOT, some studies suffered from limitations, including possible publication and referral biases, the lack of a control group, the retrospective nature and a small number of participants.

Conclusions

HBOT lowered markers of inflammation and oxidative stress and ameliorated IBD in both human and animal studies. Most treated patients were refractory to standard medical treatments. Additional studies are warranted to investigate the effects of HBOT on biomarkers of oxidative stress and inflammation as well as clinical outcomes in individuals with IBD.

Neurochem Res. 2012 Feb;37(2):436-47. Epub 2011 Oct 21.

Administration of thimerosal to infant rats increases overflow of glutamate and aspartate in the prefrontal cortex: protective role of dehydroepiandrosterone sulfate.

Duszczyk-Budhathoki M, Olczak M, Lehner M, Majewska MD.

Source

Marie Curie Chairs Program, Department of Pharmacology and Physiology of Nervous System, Institute of Psychiatry and Neurology, 02-957, Warsaw, Poland.

Abstract

Thimerosal, a mercury-containing vaccine preservative, is a suspected factor in the etiology of neurodevelopmental disorders. We previously showed that its administration to infant rats causes behavioral, neurochemical and neuropathological abnormalities similar to those present in autism. Here we examined, using microdialysis, the effect of thimerosal on extracellular levels of neuroactive amino acids in the rat prefrontal cortex (PFC). Thimerosal administration (4 injections, i.m., 240 μg Hg/kg on postnatal days 7, 9, 11, 15) induced lasting changes in amino acid overflow: an increase of glutamate and aspartate accompanied by a decrease of glycine and alanine; measured 10-14 weeks after the injections. Four injections of thimerosal at a dose of 12.5 μg Hg/kg did not alter glutamate and aspartate concentrations at microdialysis time (but based on thimerosal pharmacokinetics, could have been effective soon after its injection). Application of thimerosal to the PFC in perfusion fluid evoked a rapid increase of glutamate overflow. Coadministration of the neurosteroid, dehydroepiandrosterone sulfate (DHEAS; 80 mg/kg; i.p.) prevented the thimerosal effect on glutamate and aspartate; the steroid alone had no influence on these amino acids. Coapplication of DHEAS with thimerosal in perfusion fluid also blocked the acute action of thimerosal on glutamate. In contrast, DHEAS alone reduced overflow of glycine and alanine, somewhat potentiating the thimerosal effect on these amino acids. Since excessive accumulation of extracellular glutamate is linked with excitotoxicity, our data imply that neonatal exposure to thimerosal-containing vaccines might induce excitotoxic brain injuries, leading to neurodevelopmental disorders. DHEAS may partially protect against mercurials-induced neurotoxicity.

PMID:

 

22015977

 

[PubMed - in process] 

PMCID:

 

PMC3264864

 

Free PMC Article

Science: The GFCF Diet Works

Effectiveness of the gluten-free, casein-free diet for children diagnosed with autism spectrum disorder: Based on parental report

Authors: Pennesi Christine M.; Klein Laura Cousino

Source: Nutritional Neuroscience

Abstract:

Objectives: Studies on the gluten-free and/or casein-free (GFCF) dietary intervention for children with autism spectrum disorders (ASDs) suggest that some children may positively respond to implementation of the dietary intervention. Other research suggests that children diagnosed with ASD can be classified into subpopulations based on various factors, including gastrointestinal (GI) abnormalities and immune function.

Methods: This study analyzes parental report data collected using a 90-item online questionnaire from 387 parents or primary caregivers of children diagnosed with ASD on the efficacy of the GFCF diet. Parents reported on their child's GI symptoms, food allergy diagnoses, and suspected food sensitivities, as well as the degree and length of their diet implementation.

Results: Overall, diet efficacy among children whose parents reported the presence of GI symptoms, food allergy diagnoses, and suspected food sensitivities included greater improvement in ASD behaviors, physiological symptoms, and social behaviors compared with children whose parents reported none of these symptoms, diagnoses, or sensitivities (P < 0.05). Parental report of strict diet implementation, indicated by complete gluten/casein elimination and infrequent diet errors during and outside of parental care, also corresponded to improvement in ASD behaviors, physiological symptoms, and social behaviors (P < 0.05).

Discussion: These findings suggest that various intricacies related to diet implementation and GI and immune factors may play a role in differentiating diet responders from diet non-responders and substantiate the importance of further investigations into the various, nuanced factors that influence efficacy of the intervention among children with ASDs.

Keywords: Casein; Parental report; Autism spectrum disorder (ASD); GFCF diet; Gluten

Document Type:

DOI: http://dx.doi.org/10.1179/1476830512Y.0000000003

Hepatitis B Vaccine Can Cause Mitochondrial Disorders and Cell Death

Apoptosis. 2012 Jan 17. [Epub ahead of print]

Hepatitis B vaccine induces apoptotic death in Hepa1-6 cells.

Hamza H, Cao J, Li X, Li C, Zhu M, Zhao S.

Source

Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China, Heyam68_hamza@yahoo.com.

Abstract

Vaccines can have adverse side-effects, and these are predominantly associated with the inclusion of chemical additives such as aluminum hydroxide adjuvant. The objective of this study was to establish an in vitro model system amenable to mechanistic investigations of cytotoxicity induced by hepatitis B vaccine, and to investigate the mechanisms of vaccine-induced cell death. The mouse liver hepatoma cell line Hepa1-6 was treated with two doses of adjuvanted (aluminium hydroxide) hepatitis B vaccine (0.5 and 1 μg protein per ml) and cell integrity was measured after 24, 48 and 72 h. Hepatitis B vaccine exposure increased cell apoptosis as detected by flow cytometry and TUNEL assay. Vaccine exposure was accompanied by significant increases in the levels of activated caspase 3, a key effector caspase in the apoptosis cascade. Early transcriptional events were detected by qRT-PCR. We report that hepatitis B vaccine exposure resulted in significant upregulation of the key genes encoding caspase 7, caspase 9, Inhibitor caspase-activated DNase (ICAD), Rho-associated coiled-coil containing protein kinase 1 (ROCK-1), and Apoptotic protease activating factor 1 (Apaf-1). Upregulation of cleaved caspase 3,7 were detected by western blot in addition to Apaf-1 and caspase 9 expressions argues that cell death takes place via the intrinsic apoptotic pathway in which release of cytochrome c from the mitochondria triggers the assembly of a caspase activation complex. We conclude that exposure of Hepa1-6 cells to a low dose of adjuvanted hepatitis B vaccine leads to loss of mitochondrial integrity, apoptosis induction, and cell death, apoptosis effect was observed also in C2C12 mouse myoblast cell line after treated with low dose of vaccine (0.3, 0.1, 0.05 μg/ml). In addition In vivo apoptotic effect of hepatitis B vaccine was observed in mouse liver.

PMID:

22249285

[PubMed - as supplied by publisher]  

Mechanisms of Aluminum Adjuvant Toxicity and Autoimmunity in Pediatric Populations

Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations

Lupus (2012) 21, 223–230.

L Tomljenovic1 and CA Shaw2
1Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC,
Canada and 2Departments of Ophthalmology and Visual Sciences and Experimental Medicine and the Graduate Program in Neuroscience,
University of British Columbia, Vancouver, BC, Canada

Immune challenges during early development, including those vaccine-induced, can lead to
permanent detrimental alterations of the brain and immune function. Experimental evidence
also shows that simultaneous administration of as little as two to three immune adjuvants can
overcome genetic resistance to autoimmunity. In some developed countries, by the time children
are 4 to 6 years old, they will have received a total of 126 antigenic compounds along with
high amounts of aluminum (Al) adjuvants through routine vaccinations. According to the US
Food and Drug Administration, safety assessments for vaccines have often not included
appropriate toxicity studies because vaccines have not been viewed as inherently toxic.
Taken together, these observations raise plausible concerns about the overall safety of current
childhood vaccination programs. When assessing adjuvant toxicity in children, several key
points ought to be considered: (i) infants and children should not be viewed as ‘‘small adults’’
with regard to toxicological risk as their unique physiology makes them much more vulnerable
to toxic insults; (ii) in adult humans Al vaccine adjuvants have been linked to a variety of
serious autoimmune and inflammatory conditions (i.e., ‘‘ASIA’’), yet children are regularly
exposed to much higher amounts of Al from vaccines than adults; (iii) it is often assumed that
peripheral immune responses do not affect brain function. However, it is now clearly established
that there is a bidirectional neuro-immune cross-talk that plays crucial roles in immunoregulation
as well as brain function. In turn, perturbations of the neuro-immune axis have
been demonstrated in many autoimmune diseases encompassed in ‘‘ASIA’’ and are thought to
be driven by a hyperactive immune response; and (iv) the same components of the neuroimmune
axis that play key roles in brain development and immune function are heavily targeted
by Al adjuvants. In summary, research evidence shows that increasing concerns about
current vaccination practices may indeed be warranted. Because children may be most at risk
of vaccine-induced complications, a rigorous evaluation of the vaccine-related adverse health
impacts in the pediatric population is urgently needed.


[ed note: emphasis mine]

Thimerosal Gives Baby Rats Brain Damage

Lasting neuropathological changes in rat brain after intermittent neonatal administration of thimerosal.

Folia Neuropathol. 2010;48(4):258-69.  Olczak M, Duszczyk M, Mierzejewski P, Wierzba-Bobrowicz T, Majewska MD.

Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, ul. Sobieskiego 9, Warsaw, Poland.

Abstract
Thimerosal, an organomercurial added as a preservative to some vaccines, is a suspected iatrogenic factor, possibly contributing to paediatric neurodevelopmental disorders including autism. We examined the effects of early postnatal administration of thimerosal (four i.m. injections, 12 or 240 μg THIM-Hg/kg, on postnatal days 7, 9, 11 and 15) on brain pathology in Wistar rats. Numerous neuropathological changes were observed in young adult rats which were treated postnatally with thimerosal. They included: ischaemic degeneration of neurons and "dark" neurons in the prefrontal and temporal cortex, the hippocampus and the cerebellum, pathological changes of the blood vessels in the temporal cortex, diminished synaptophysin reaction in the hippocampus, atrophy of astroglia in the hippocampus and cerebellum, and positive caspase-3 reaction in Bergmann astroglia. These findings document neurotoxic effects of thimerosal, at doses equivalent to those used in infant vaccines or higher, in developing rat brain, suggesting likely involvement of this mercurial in neurodevelopmental disorders.

J Inorg Biochem. 2011 Nov;105(11):1489-99. Epub 2011 Aug 23.

Do aluminum vaccine adjuvants contribute to the rising prevalence of autism?

Tomljenovic L, Shaw CA.

Source

Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British Columbia, 828 W. 10th Ave, Vancouver, BC, Canada V5Z 1L8.

Abstract
Autism spectrum disorders (ASD) are serious multisystem developmental disorders and an urgent global public health concern. Dysfunctional immunity and impaired brain function are core deficits in ASD. Aluminum (Al), the most commonly used vaccine adjuvant, is a demonstrated neurotoxin and a strong immune stimulator. Hence, adjuvant Al has the potential to induce neuroimmune disorders. When assessing adjuvant toxicity in children, two key points ought to be considered: (i) children should not be viewed as "small adults" as their unique physiology makes them much more vulnerable to toxic insults; and (ii) if exposure to Al from only few vaccines can lead to cognitive impairment and autoimmunity in adults, is it unreasonable to question whether the current pediatric schedules, often containing 18 Al adjuvanted vaccines, are safe for children? By applying Hill's criteria for establishing causality between exposure and outcome we investigated whether exposure to Al from vaccines could be contributing to the rise in ASD prevalence in the Western world. Our results show that: (i) children from countries with the highest ASD prevalence appear to have the highest exposure to Al from vaccines; (ii) the increase in exposure to Al adjuvants significantly correlates with the increase in ASD prevalence in the United States observed over the last two decades (Pearson r=0.92, p<0.0001); and (iii) a significant correlation exists between the amounts of Al administered to preschool children and the current prevalence of ASD in seven Western countries, particularly at 3-4months of age (Pearson r=0.89-0.94, p=0.0018-0.0248). The application of the Hill's criteria to these data indicates that the correlation between Al in vaccines and ASD may be causal. Because children represent a fraction of the population most at risk for complications following exposure to Al, a more rigorous evaluation of Al adjuvant safety seems warranted.

Apparently Your Tongue Goes Down Your GI Tract and Up To Your Brain

J Pediatr Gastroenterol Nutr. 2011 Aug 8. [Epub ahead of print]

From The Tongue To The Gut.

Negri R, Morini G, Greco L.

* European Laboratory for Food Induced Diseases, University of Naples Federico II, Naples, Italy † University of Gastronomic Sciences, Pollenzo-Bra (CN), Italy.
Abstract

ABSTRACT: The physiology of human taste enjoyed an unprecedented expansion of knowledge brought forward by modern genetics and molecular biology. In the last 10 years the cellular organization of taste receptors from taste buds distributed in the various papillae of the tongue and the soft palate was enlightened. This molecular revolution rapidly expanded over and above the tongue, since several papers reporting the presence of taste receptors in non-gustatory tissues (like the gut and the brain) appeared. Hence the issue of perception of food molecules is not anymore confined to the field of nutrition and food preferences, but is rapidly expanding to gastrointestinal function and, possibly, to gut dysfunction too. In children functional gastrointestinal diseases are strictly correlated to food preference and food aversion and up to now the tools to face these kind of problems were the basic nutritional requirements, familial good sense and a lot of patience: blunt tools to face very common and disturbing complaints. The fact that taste receptors are expressed down the whole of intestinal tract is of particular interest, because of their possible role in digestive behavior and absorption of nutrients; therefore recent and future discoveries in this field will make possible to fine-tune new, sharper tools to face children with functional gastrointestinal diseases.

PMID:

 

21832948

 

[PubMed - as supplied by publisher]

ASD, GI, Immune Abnormalities

Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes 

Harumi Jyonouchia, Lee Genga, Deanna L. Streckb and Gokce A. Torunerb

Division of Allergy/Immunology and Infection Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School (NJMS), 185 South Orange Ave, Newark, NJ, United States

Institute of Genomic Medicine, Department of Pediatrics, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School (NJMS), 185 South Orange Ave, Newark, NJ, United States

Received 16 February 2011; revised 26 June 2011; accepted 6 July 2011. Available online 30 July 2011.

Abstract

Innate/adaptive immune responses and transcript profiles of peripheral blood monocytes were studied in ASD children who exhibit fluctuating behavioral symptoms following infection and other immune insults (ASD/Inf, N = 30). The ASD/Inf children with persistent gastrointestinal symptoms (ASD/Inf + GI, N = 19), revealed less production of proinflammatory and counter-regulatory cytokines with stimuli of innate immunity and marked changes in transcript profiles of monocytes as compared to ASD/no-Inf (N = 28) and normal (N = 26) controls. This included a 4–5 fold up-regulation of chemokines (CCL2 and CCL7), consistent with the production of more CCL2 by ASD/Inf + GI cells. These results indicate dysregulated innate immune defense in the ASD/Inf + GI children, rendering them more vulnerable to common microbial infection/dysbiosis and possibly subsequent behavioral changes.

Ancestry of Pink Disease (Infantile Acrodynia) a Risk Factor for Autism

Ancestry of pink disease (infantile acrodynia) identified as a risk factor for autism spectrum disorders.

J Toxicol Environ Health A. 2011 Sep 15;74(18):1185-94. Shandley K, Austin DW.

Swinburne Autism Bio-Research Initiative (SABRI), Brain and Psychological Sciences Research Centre , Swinburne University of Technology , Hawthorn , Victoria , Australia.

Abstract
Pink disease (infantile acrodynia) was especially prevalent in the first half of the 20th century. Primarily attributed to exposure to mercury (Hg) commonly found in teething powders, the condition was developed by approximately 1 in 500 exposed children. The differential risk factor was identified as an idiosyncratic sensitivity to Hg. Autismspectrum disorders (ASD) have also been postulated to be produced by Hg. Analogous to the pink disease experience, Hg exposure is widespread yet only a fraction of exposed children develop an ASD, suggesting sensitivity to Hg may also be present in children with an ASD. The objective of this study was to test the hypothesis that individuals with a known hypersensitivity to Hg (pink disease survivors) may be more likely to have descendants with an ASD. Five hundred and twenty-two participants who had previously been diagnosed with pink disease completed a survey on the health outcomes of their descendants. The prevalence rates of ASD and a variety of other clinical conditions diagnosed in childhood (attention deficit hyperactivity disorder, epilepsy, Fragile X syndrome, and Down syndrome) were compared to well-established general population prevalence rates. The results showed the prevalence rate of ASD among the grandchildren of pink disease survivors (1 in 22) to be significantly higher than the comparable general population prevalence rate (1 in 160). The results support the hypothesis that Hg sensitivity may be a heritable/genetic risk factor for ASD.

Research Review Finds Vaccine Encephalopathy One Cause of Autism

Theoretical aspects of autism: Causes—A review

Journal of Immunotoxicology, January-March 2011, Vol. 8, No. 1 , Pages 68-79

Helen V. Ratajczak, PhD

Autism, a member of the pervasive developmental disorders (PDDs), has been increasing dramatically since its description by Leo Kanner in 1943. First estimated to occur in 4 to 5 per 10,000 children, the incidence of autism is now 1 per 110 in the United States, and 1 per 64 in the United Kingdom, with similar incidences throughout the world. Searching information from 1943 to the present in PubMed and Ovid Medline databases, this review summarizes results that correlate the timing of changes in incidence with environmental changes. Autism could result from more than one cause, with different manifestations in different individuals that share common symptoms. Documented causes of autism include genetic mutations and/or deletions, viral infections, and encephalitis following vaccination. Therefore, autism is the result of genetic defects and/or inflammation of the brain. The inflammation could be caused by a defective placenta, immature blood-brain barrier, the immune response of the mother to infection while pregnant, a premature birth, encephalitis in the child after birth, or a toxic environment.

CBS reports on the study:

Vaccines and autism: a new scientific review
by CBS News investigative correspondent Sharyl Attkisson.

For all those who've declared the autism-vaccine debate over - a new scientific review begs to differ. It considers a host of peer-reviewed, published theories that show possible connections between vaccines and autism.

The article in the Journal of Immunotoxicology is entitled "Theoretical aspects of autism: Causes--A review." The author is Helen Ratajczak, surprisingly herself a former senior scientist at a pharmaceutical firm. Ratajczak did what nobody else apparently has bothered to do: she reviewed the body of published science since autism was first described in 1943. Not just one theory suggested by research such as the role of MMR shots, or the mercury preservative thimerosal; but all of them.

Ratajczak's article states, in part, that "Documented causes of autism include genetic mutations and/or deletions, viral infections, and encephalitis [brain damage] following vaccination [emphasis added]. Therefore, autism is the result of genetic defects and/or inflammation of the brain."

The article goes on to discuss many potential vaccine-related culprits, including the increasing number of vaccines given in a short period of time. "What I have published is highly concentrated on hypersensitivity, Ratajczak told us in an interview, "the body's immune system being thrown out of balance."

University of Pennsylvania's Dr. Brian Strom, who has served on Institute of Medicine panels advising the government on vaccine safety says the prevailing medical opinion is that vaccines are scientifically linked to encephalopathy (brain damage), but not scientifically linked to autism. As for Ratajczak's review, he told us he doesn't find it remarkable. "This is a review of theories. Science is based on facts. To draw conclusions on effects of an exposure on people, you need data on people. The data on people do not support that there is a relationship. As such, any speculation about an explanation for a (non-existing) relationship is irrelevant."

Ratajczak also looks at a factor that hasn't been widely discussed: human DNA contained in vaccines. That's right, human DNA. Ratajczak reports that about the same time vaccine makers took most thimerosal out of most vaccines (with the exception of flu shots which still widely contain thimerosal), they began making some vaccines using human tissue. Ratajczak says human tissue is currently used in 23 vaccines. She discusses the increase in autism incidence corresponding with the introduction of human DNA to MMR vaccine, and suggests the two could be linked. Ratajczak also says an additional increased spike in autism occurred in 1995 when chicken pox vaccine was grown in human fetal tissue.

Why could human DNA potentially cause brain damage? The way Ratajczak explained it to me: "Because it's human DNA and recipients are humans, there's homologous recombinaltion tiniker. That DNA is incorporated into the host DNA. Now it's changed, altered self and body kills it. Where is this most expressed? The neurons of the brain. Now you have body killing the brain cells and it's an ongoing inflammation. It doesn't stop, it continues through the life of that individual."

Dr. Strom said he was unaware that human DNA was contained in vaccines but told us, "It does not matter...Even if human DNA were then found in vaccines, it does not mean that they cause autism." Ratajczak agrees that nobody has proven DNA causes autism; but argues nobody has shown the opposite, and scientifically, the case is still open.

A number of independent scientists have said they've been subjected to orchestrated campaigns to discredit them when their research exposed vaccine safety issues, especially if it veered into the topic of autism. We asked Ratajczak how she came to research the controversial topic. She told us that for years while working in the pharmaceutical industry, she was restricted as to what she was allowed to publish. "I'm retired now," she told CBS News. "I can write what I want."

We wanted to see if the CDC wished to challenge Ratajczak's review, since many government officials and scientists have implied that theories linking vaccines to autism have been disproven, and Ratajczak states that research shows otherwise. CDC officials told us that "comprehensive review by CDC...would take quite a bit of time." In the meantime, CDC provided these links:

Interagency Autism Coordination Committee: http://iacc.hhs.gov

Overview of all CDC surveillance and epi work: http://www.cdc.gov/ncbddd/autism/research.html

CDC study on risk factors and causes: http://www.cdc.gov/ncbddd/autism/seed.html

JAMA Confirms that Mitochondrial Dysfunction at Play in Autism

From the Journal of the American Medical Association:

Mitochondrial Dysfunction in Autism

1. Cecilia Giulivi, PhD;
2. Yi-Fan Zhang, BS;
3. Alicja Omanska-Klusek, MS;
4. Catherine Ross-Inta, BS;
5. Sarah Wong, BS;
6. Irva Hertz-Picciotto, PhD;
7. Flora Tassone, PhD;
8. Isaac N. Pessah, PhD

[+] Author Affiliations

1.
Author Affiliations: Department of Molecular Biosciences, School of Veterinary Medicine (Drs Giulivi and Pessah, Mr Zhang, and Mss Omanska-Klusek, Ross-Inta, and Wong), Departments of Public Health Sciences (Dr Hertz-Picciotto) and Biochemistry and Molecular Medicine (Dr Tassone), School of Medicine (Drs Hertz-Picciotto and Tassone), and Center for Children's Environmental Health and Disease Prevention (Drs Hertz-Picciotto and Pessah), and Medical Investigations of Neurodevelopmental Disorders Institute (Drs Hertz-Picciotto, Tassone, and Pessah), University of California, Davis.

Abstract

Context Impaired mitochondrial function may influence processes highly dependent on energy, such as neurodevelopment, and contribute to autism. No studies have evaluated mitochondrial dysfunction and mitochondrial DNA (mtDNA) abnormalities in a well-defined population of children with autism.

Objective To evaluate mitochondrial defects in children with autism.

Design, Setting, and Patients Observational study using data collected from patients aged 2 to 5 years who were a subset of children participating in the Childhood Autism Risk From Genes and Environment study in California, which is a population-based, case-control investigation with confirmed autism cases and age-matched, genetically unrelated, typically developing controls, that was launched in 2003 and is still ongoing. Mitochondrial dysfunction and mtDNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls.

Main Outcome Measures Oxidative phosphorylation capacity, mtDNA copy number and deletions, mitochondrial rate of hydrogen peroxide production, and plasma lactate and pyruvate.

Results The reduced nicotinamide adenine dinucleotide (NADH) oxidase activity (normalized to citrate synthase activity) in lymphocytic mitochondria from children with autism was significantly lower compared with controls (mean, 4.4 [95% confidence interval {CI}, 2.8-6.0] vs 12 [95% CI, 8-16], respectively; P = .001). The majority of children with autism (6 of 10) had complex I activity below control range values. Higher plasma pyruvate levels were found in children with autism compared with controls (0.23 mM [95% CI, 0.15-0.31 mM] vs 0.08 mM [95% CI, 0.04-0.12 mM], respectively; P = .02). Eight of 10 cases had higher pyruvate levels but only 2 cases had higher lactate levels compared with controls. These results were consistent with the lower pyruvate dehydrogenase activity observed in children with autism compared with controls (1.0 [95% CI, 0.6-1.4] nmol × [min × mg protein]−1 vs 2.3 [95% CI, 1.7-2.9] nmol × [min × mg protein]−1, respectively; P = .01). Children with autism had higher mitochondrial rates of hydrogen peroxide production compared with controls (0.34 [95% CI, 0.26-0.42] nmol × [min × mg of protein]−1 vs 0.16 [95% CI, 0.12-0.20] nmol × [min × mg protein]−1 by complex III; P = .02). Mitochondrial DNA overreplication was found in 5 cases (mean ratio of mtDNA to nuclear DNA: 239 [95% CI, 217-239] vs 179 [95% CI, 165-193] in controls; P = 10−4). Deletions at the segment of cytochrome b were observed in 2 cases (ratio of cytochrome b to ND1: 0.80 [95% CI, 0.68-0.92] vs 0.99 [95% CI, 0.93-1.05] for controls; P = .01).

Conclusion In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than typically developing children.

Urinary Porphyrin Excretion in Neurotypical and Autistic Children

Environ Health Perspect. 2010 Oct;118(10):1450-7. Epub 2010 Jun 24.
Urinary porphyrin excretion in neurotypical and autistic children.

Woods JS, Armel SE, Fulton DI, Allen J, Wessels K, Simmonds PL, Granpeesheh D, Mumper E, Bradstreet JJ, Echeverria D, Heyer NJ, Rooney JP.

Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98105, USA. jwoods@u.washington.edu
Abstract

BACKGROUND: Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).

OBJECTIVES: This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.

METHODS: This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.

RESULTS: Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.

CONCLUSIONS: These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.

Urinary Porphyrin Excretion in Neurotypical and Autistic Children
Medscape
Comparison of Urinary Porphyrins in NT and AU Children

Our findings suggest that mean concentrations of uro- and precoproporphyrins are comparable between NT and AU children of the same age ranges. In contrast, the concentrations of all remaining porphyrins, particularly hexacarboxyl-, pentacarboxyl-, and coproporphyrins, were significantly higher in AU children than NT children, especially in older age groups. Several possibilities might account for these differences. Of initial concern, Hg exposure appears unlikely to play a role in this effect, because no significant differences were observed between NT and AU subjects for indices of past exposure to Hg from dental or medical sources, as reported by parents/caregivers. Additionally, urinary Hg concentrations, measures of recent Hg exposure, were very low among all subjects in this study (Table 2), and no significant differences between diagnostic groups were observed. As noted recently (Woods et al. 2009a), incipient although statistically nonsignificant changes in urinary porphyrin concentrations were seen among children with urinary Hg concentrations derived from prolonged dental amalgam Hg exposure on the order of 3.2 µg/g creatinine. This is nearly 10 times the mean urinary Hg concentration observed among children in this study. Similar findings describing very low blood Hg levels and insignificant differences between NT and AU children have recently been reported (Hertz-Picciotto et al. 2010). These observations do not preclude a possible role of Hg exposure from sources not measured or validated in the present study, especially during the perinatal period, in the etiology of autism or related neurodevelopmental disorders in some children, particularly in relation to genetic variation that may predispose to increased risk of the neurotoxic effects of Hg as Hg0 as reported in adults (Echeverria et al. 2005, 2006, 2010; Heyer et al. 2009). Our findings indicate instead that porphyrin metabolism, particularly in preadolescent children, may be too disordered or differently regulated to permit detection of the Hg-mediated changes in urinary porphyrin excretion apparent in adult subjects. Further studies using a substantially larger population, such as the National Children's Study now in progress (National Children's Study 2010), are required to resolve this question.

Thimerosal Impairs Opioid System in Rats

Neonatal administration of a vaccine preservative, thimerosal, produces lasting impairment of nociception and apparent activation of opioid system in rats.

Brain Res. 2009 Dec 8;1301:143-51. Epub 2009 Sep 9.

Olczak M, Duszczyk M, Mierzejewski P, Majewska MD. Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.

Abstract

Thimerosal (THIM), an organomercury preservative added to many child vaccines is a suspected factor in pathogenesis of neurodevelopmental disorders. We examined the pharmacokinetics of Hg in the brain, liver and kidneys after i.m. THIM injection in suckling rats and we tested THIM effect on nociception. THIM solutions were injected to Wistar and Lewis rats in a vaccination-like mode on PN days 7, 9, 11 and 15 in four equal doses. For Wistar rats these were: 12, 48, 240, 720, 1440, 2160, 3000 microg Hg/kg and for Lewis: 54, 216, 540 and 1080 microg Hg/kg. Pharmacokinetic analysis revealed that Hg from THIM injections accumulates in the rat brain in significant amounts and remains there longer than 30 days after the injection. At the 6th week of age animals were examined for pain sensitivity using the hot plate test. THIM treated rats of both strains and sexes manifested statistically significantly elevated pain threshold (latency for paw licking, jumping) on a hot plate (56 degrees C). Wistar rats were more sensitive to this effect than Lewis rats. Protracted THIM-induced hypoalgesia was reversed by naloxone (5 mg/kg, i.p.) injected before the hot plate test, indicative of involvement of endogenous opioids. This was confirmed by augmented catalepsy after morphine (2.5 mg/kg, s.c.) injection. Acute THIM injection to 6-week-old rats also produced hypoalgesia, but this effect was transient and was gone within 14 days. Present findings show that THIM administration to suckling or adult rats impairs sensitivity to pain, apparently due to activation the endogenous opioid system.

Neonatal Administration of Thimerosal Causes Persistent Changes in Mu Opioid Receptors in the Rat Brainst

Neurochem Res. 2010 Aug 28.

Neonatal Administration of Thimerosal Causes Persistent Changes in Mu Opioid Receptors in the Rat Brain.

Olczak M, Duszczyk M, Mierzejewski P, Bobrowicz T, Majewska MD.

Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Sobieskiego 9 str., 02-957, Warsaw, Poland.

Abstract

Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders. Our previous study showed that thimerosal administered to suckling rats causes persistent, endogenous opioid-mediated hypoalgesia. Here we examined, using immunohistochemical staining technique, the density of mu-opioid receptors (MORs) in the brains of rats, which in the second postnatal week received four i.m. injections of thimerosal at doses 12, 240, 1,440 or 3,000 mug Hg/kg. The periaqueductal gray, caudate putamen and hippocampus were examined. Thimerosal administration caused dose-dependent statistically significant increase in MOR densities in the periaqueductal gray and caudate putamen, but decrease in the dentate gyrus, where it was accompanied by the presence of degenerating neurons and loss of synaptic vesicle marker (synaptophysin). These data document that exposure to thimerosal during early postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development.

Full article:  http://www.springerlink.com/content/d751p01x01013627/fulltext.pdf