Autism Study Reveals No Genetic Associations

Autism spectrum disorders (ASD) include everything from the relatively mild Asperger syndrome (characterized by more mild social and language impairments) to full-fledged autism (characterized by severe social and communicative handicaps, limited interests, and repetitive behaviors).  ASD is relatively common, and in the United States it is estimated that one out of every 54 boys is affected (the frequency in girls is considerably lower, averaging one affected girl out of every 252). Although genetics certainly plays a role in these conditions, exactly how is not fully understood, and this newest study, led by Richard Anney (Trinity College of Dublin) and Bernie Devlin (University of Pittsburgh School of Medicine), is the next a long line of scientific inquiries to this point.

Their study, known as the Autism Genome Project (AGP), was conducted in two stages. The first stage of consisted of a genome-wide association study using genetic data from 1400 families affected by autism; the second stage checked the associations discovered in the first stage using the genetic data from an additional 1301 ASD-affected families and included another new genome-wide association study which combined the study subjects from both stages.

When all the analyses were said and done, no SNPs (common genetic variations) were significantly associated with ASD. Furthermore, when some of the SNPs that had been identified in the first study as possibly associated with ASD were tested in the second-stage families, the associations failed to hold up.  This lack of common SNPs associated with ASD is both disappointing and enlightening.

Knowledge of what is not true, paradoxically, is knowledge of what is true.  For instance, if I tell you that my pet Tyger is not a dog, you are one step closer to knowing Tyger’s a cat.  Most of science progresses through “not trues” — the failed hypotheses that bring us closer to real understanding. A perfect example of this mode of scientific progress is this recent genetic study.  Their lack of findings was quite a finding.

The fact that no SNPs were associated with ASD in such a large study suggests that the effect of any one common SNP is quite small. Even when all the SNPs were used together to predict whether a study subject would have ASD, the model explained less than 1% of differences in risk for the condition.

The fact that these common SNPs have little power to predict ASD does not mean that genetics is unimportant.  Twin studies suggest that ASD is at least moderately heritable, suggesting that genetics does play a role.  This current study’s lack of findings supports the idea that common genetic variations may play a smaller role than rare mutations or copy number variation (the number of copies of a given gene) in ASD risk. Thus, the lack of ASD associations today has, hopefully, brought us closer to tomorrow’s discoveries.

via No Genetic Associations Found in Autism GWAS | The Spittoon.

War of the Worlds: The Flu Saga

The World of Flu as Manipulated by the CDC

by David Burd

http://www.ageofautism.com/2012/08/the-world-of-flu-as-manipulated-by-the-cdc.html

War of the Worlds

Until three years ago and the Swine/H1N1 Summer Panic in 2009,  for over ten years U.S. Government Health officials had designated the first week of December as National Flu Shot Week. The data for Summer 2009 shows blood tests for flu were performed by the millions as compared to “normal” years when such tests were not performed at all until late Fall. Never mind that an edict dictated virtually all blood results to be arbitrarily declared to be H1N1 and all the other flu variants shoved into the H1N1 category.  Never mind that all flu variants have always been omnipresent all year long, just not tested for until late Fall.

Never mind countries such as Canada, where parents are more skeptical about the shots, pediatric flu- associated mortality is but a small fraction per-capita that of the U.S.  Never mind CDC officials declared there was no risk whatsoever from the multiple batch shot lots preserved with mercury and urged on an unwitting American public.

Never mind in 2009 that  TV doctor personality Nancy Snyderman declared on national TV for all Americans to “just get your damn flu shot.”

Never mind that every year since 2003 when flu shots were sometimes put on fast-track promotion as early as  September that U.S. pediatric flu-associated deaths those years also spiked.  Never mind (see my post in Age of Autism, June 2, 2010) that U.S.  protocols for treating kids hospitalized for flu to be dosed with the chemotherapy antiviral drug Ribavirin, a drug that ALWAYS destroys red blood cells thus causing hemolytic anemia – never mind no other country in the world is insane enough to employ this protocol.

Never mind the great Flu Shot Shortage in the Winter of 2004-2005, when British factories supplying U.S. flu shots were shut down, and this coincided with the lowest pediatric flu-associated deaths on record, until this last 2011-2012 season when data shows U.S. parents largely avoided flu shots for their children after realizing how dangerous the shots were, and are, especially when they realized CDC says TWO flu shots be given to infants at 6 and 7 months respectively, each one loaded with mercury unless a non-mercury shot be explicitly demanded.

Never mind that all the other vaccine ingredients, called excipients, are all toxic to humans, magnified as least 10-fold in vulnerable undeveloped infants who are but one-twentieth the weight of adults but get shots of 25 milliliters compared to an adult dose of 50 milliliters and who have mature, hardened systems compared to newborn 6-month olds.

Never mind that vaccine batches may have unknown contaminants, or may be improperly stored, or that Australia two years ago in Spring, 2010, a national emergency abruptly stopped all flu shots for kids when massive numbers of convulsing children were rushed to hospitals after getting their flu shots.  Never mind the bought-off U.S. mainstream media suppressed the Australian episode, keeping ignorant the American public, never mind this was kept mum by  “just get your damn flu shot” Dr. Nancy Snyderman.

Never mind that well nourished mothers breast feeding their babies supply all the necessary protection against such as flu, never mind that the vast majority of American babies taken to hospitals with flu had serious chronic health pre-conditions and/or were significantly premature.  Never mind that any serious health condition in U.S. babies is declared by CDC as always a mere coincidence having nothing to do with massive amounts of recently injected toxic vaccine ingredients as from the flu vaccine.

Which brings me back to the present: Here in late July, 2012, my local Rite Aid drugstore in Alexandria, Virginia has plastered its interior  aisles with countless flu-shot promotion posters to go along with gigantic outdoor posters.  Whatever happened to the December National Flu Shot promotion week?

David M. Burd        Alexandria, Virginia      August 12, 2012

The Science on Autism, Mitochondria, and Mercury

699 - Puzzle-Pastel - Pattern

 (Photo credit: Patrick Hoesly)

From  Safe Minds (http://www.safeminds.org/research/science-autism-mitochondria-mercury.html)

The U.S government has conceded a case in the Vaccine Injury Court. The case is a child diagnosed with autism who has a mitochondrial disorder. The child’s vaccinations triggered an adverse effect that led to her autism. David Kirby, author of Evidence of harm, has written an extensive article on the Huffington Post about the case and its implications.

Kirby mentions that mercury, including thimerosal, can trigger mitochondrial dysfunction. Mercury can also lead to oxidative stress (OS) and calcium (Ca2+) dysregulation, both of which are key features of mitochondrial dysfunction. Several studies have linked increased OS, Ca2+ imbalance, and mitochondrial dysfunction to autism.

Also, read David Kirby’s interview with Imus on WABC Radio.

To help readers understand the science relevant to this court case, SafeMinds has posted an assortment of research articles (in full or the abstracts) that pertain to mitochondria function, related physiology (that is, calcium homeostasis and oxidative stress), mercury (including thimerosal) and autism.

Dr. Jon Poling to Dr. Steven Novella on Age of Autism

By Dr. Jon Poling, father of Hannah Poling.

OPEN LETTER TO DR. STEVEN NOVELLA IN RESPONSE TO
“Has the Government Conceded Vaccines Cause Autism?”

Dr. Novella,
Thank you for generating interesting discussion regarding my little girl, Hannah Poling.  I would like to give you additional information in order to generate further productive discussions on this matter amongst the neurology community.  This information should assist you, Dr. DiMauro, and Dr. Trevethan, who have also commented publicly, to formulate better theories as to the significance of Hannah’s mitochondrial dysfunction in relation to her autism.
1. Mito Dysfunction or Mito Disease?  Chicken or Egg?

READ THE ENTIRE LETTER

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Uncoupling of ATP-Mediated Calcium Signaling and Dysregulated Interleukin-6 Secretion in Dendritic Cells by Nanomolar Thimerosal
Samuel R. Goth,1,2 Ruth A. Chu,2 Jeffrey P. Gregg,1,3,4 Gennady Cherednichenko,2 and Isaac N. Pessah1,2,4

1National Institute of Environmental Health Sciences Center for Children’s Environmental Health, 2Department of Veterinary Molecular Biosciences, and 3Department of Medical Pathology, University of California-Davis, Davis, California, USA; 4MIND (Medical Investigation of Neurodevelopmental Disorders) Institute, University of California-Davis, Sacramento, California, USA

Abstract
Dendritic cells (DCs) , a rare cell type widely distributed in the soma, are potent antigen-presenting cells that initiate primary immune responses. DCs rely on intracellular redox state and calcium (Ca2+) signals for proper development and function, but the relationship between these two signaling systems is unclear. Thimerosal (THI) is a mercurial used to preserve vaccines and consumer products, and is used experimentally to induce Ca2+ release from microsomal stores. We tested adenosine triphosphate (ATP) -mediated Ca2+ responses of DCs transiently exposed to nanomolar THI. Transcriptional and immunocytochemical analyses show that murine myeloid immature DCs (IDCs) and mature DCs (MDCs) express inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) Ca2+ channels, known targets of THI. IDCs express the RyR1 isoform in a punctate distribution that is densest near plasma membranes and within dendritic processes, whereas IP3Rs are more generally distributed. RyR1 positively and negatively regulates purinergic signaling because ryanodine (Ry) blockade a) recruited 80% more ATP responders, b) shortened ATP-mediated Ca2+ transients > 2-fold, and c) produced a delayed and persistent rise (≥ 2-fold) in baseline Ca2+. THI (100 nM, 5 min) recruited more ATP responders, shortened the ATP-mediated Ca2+ transient (≥ 1.4-fold) , and produced a delayed rise (≥ 3-fold) in the Ca2+ baseline, mimicking Ry. THI and Ry, in combination, produced additive effects leading to uncoupling of IP3R and RyR1 signals. THI altered ATP-mediated interleukin-6 secretion, initially enhancing the rate of cytokine secretion but suppressing cytokine secretion overall in DCs.DCs are exquisitely sensitive to THI, with one mechanism involving the uncoupling of positive and negative regulation of Ca2+ signals contributed by RyR1. Key words: calcium, calcium channel, dendritic cell, ethyl mercury, immunotoxicity, interleukin-6, organic mercury, redox, thimerosal. Environ Health Perspect 114:1083-1091 (2006) . doi:10.1289/ehp.8881 available via http://dx.doi.org/ [Online 21 March 2006]

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Pharmacol Res. 2005 Oct;52(4):328-33.
Thimerosal-induced cytosolic Ca2+ elevation and subsequent cell death in human osteosarcoma cells.
Chang HTLiu CSChou CTHsieh CHChang CHChen WCLiu SIHsu SSChen JS, Jiann BPJan CR.
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.

The effect of the oxidizing agent thimerosal on cytosolic free Ca(2+) concentration ([Ca(2+)]i) and proliferation has not been explored in human osteoblast-like cells. This study examined whether thimerosal alters Ca(2+) levels and causes cell death in MG63 human osteosarcoma cells. [Ca(2+)]i and cell death were measured using the fluorescent dyes fura-2 and WST-1, respectively. Thimerosal at concentrations above 5 microM increased [Ca(2+)]i in a concentration-dependent manner. The Ca(2+) signal was reduced by 80% by removing extracellular Ca(2+). The thimerosal-induced Ca(2+) influx was sensitive to blockade of La(3+), and dithiothreitol (50 microM) but was insensitive to nickel and several L-type Ca(2+) channel blockers. After pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor), thimerosal failed to induce [Ca(2+)]i rises. Inhibition of phospholipase C with 2 microM U73122 did not change thimerosal-induced [Ca(2+)]i rises. At concentrations of 5, 10 and 20 microM thimerosal killed 33, 55 and 100% cells, respectively. The cytotoxic effect of 5 microM thimerosal was reversed by 54% by prechelating cytosolic Ca(2+) with BAPTA. Collectively, in MG63 cells, thimerosal induced a [Ca(2+)]i rise by causing Ca(2+) release from endoplasmic reticulum stores and Ca(2+) influx from extracellular space. Furthermore, thimerosal can cause Ca(2+)-related cytotoxicity in a concentration-dependent manner.

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Toxicology. 2004 Jan 15;195(1):77-84.
Effect of thimerosal, a preservative in vaccines, on intracellular Ca2+ concentration of rat cerebellar neurons.
Ueha-Ishibashi TOyama YNakao HUmebayashi CNishizaki YTatsuishi TIwase KMurao KSeo H.
Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.

The effect of thimerosal, an organomercurial preservative in vaccines, on cerebellar neurons dissociated from 2-week-old rats was compared with those of methylmercury using a flow cytometer with appropriate fluorescent dyes. Thimerosal and methylmercury at concentrations ranging from 0.3 to 10 microM increased the intracellular concentration of Ca2+ ([Ca2+]i) in a concentration-dependent manner. The potency of 10 microM thimerosal to increase the [Ca2+]i was less than that of 10 microM methylmercury. Their effects on the [Ca2+]i were greatly attenuated, but not completely suppressed, under external Ca(2+)-free condition, suggesting a possibility that both agents increase membrane Ca2+ permeability and release Ca2+ from intracellular calcium stores. The effect of 10 microM thimerosal was not affected by simultaneous application of 30 microM L-cysteine whereas that of 10 microM methylmercury was significantly suppressed. The potency of thimerosal was similar to that of methylmercury in the presence of L-cysteine. Both agents at 1 microM or more similarly decreased the cellular content of glutathione in a concentration-dependent manner, suggesting an increase in oxidative stress. Results indicate that thimerosal exerts some cytotoxic actions on cerebellar granule neurons dissociated from 2-week-old rats and its potency is almost similar to that of methylmercury.

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Curr Opin Neurobiol. 2007 Feb;17(1):112-9. Epub 2007 Feb 1.
Molecular mechanisms of autism: a possible role for Ca2+ signaling.
Krey JFDolmetsch RE.
Autism spectrum disorders (ASDs) are a group of developmental disorders characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. The molecular mechanisms that underlie ASDs are not known, but several recent developments suggest that some forms of autism are caused by failures in activity-dependent regulation of neural development. Mutations of several voltage-gated and ligand-gated ion channels that regulate neuronal excitability and Ca2+ signaling have been associated with ASDs. In addition, Ca2+-regulated signaling proteins involved in synapse formation and dendritic growth have been implicated in ASDs. These recent advances suggest a set of signaling pathways that might have a role in generating these increasingly prevalent disorders.

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Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
Volume 423, Issues 1-2, 25 January 1999, Pages 65-72

Uptake, cellular distribution and DNA damage produced by mercuric chloride in a human fetal hepatic cell line

Leticia Bucio, Cecilia García, Verónica Souza, Elizabeth Hernández, Cristina González, Miguel Betancourt and Ma. Concepción Gutiérrez-Ruiz

Abstract
A human hepatic cell line (WRL-68 cells) was employed to investigate the uptake of the toxic heavy metal mercury. Hg accumulation in WRL-68 cells is a time and concentration dependent process. A rapid initial phase of uptake was followed by a second slower phase. The transport does not require energy and at low HgCl2 concentrations (<50 μM) Hg transport occurs by temperature-insensitive processes. Subcellular distribution of Hg was: 48% in mitochondria, 38% in nucleus and only 8% in cytosolic fraction and 7% in microsomes. Little is known at the molecular level concerning the genotoxic effects following the acute exposure of eucaryotic cells to low concentrations of Hg. Our results showed that Hg induced DNA single-strand breaks or alkali labile sites using the single-cell gel electrophoresis assay (Comet assay). The percentage of damaged nucleus and the average length of DNA migration increased as metal concentration and time exposure increased. Lipid peroxidation, determined as malondialdehyde production in the presence of thiobarbituric acid, followed the same tendency, increased as HgCl2 concentration and time of exposure increased. DNA damage recovery took 8 h after partial metal removed with PBS–EGTA.

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Naviaux RK.  The spectrum of mitochondrial disease, in Mitochondrial and Metabolic Disorders-a primary care physician’s guide. Psy-Ed Corp., Oradell, NJ, pp. 3-10, 1997.

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Mutagenesis, Vol. 15, No. 6, 525-530, November 2000
Mutagenicity of mercury chloride and mechanisms of cellular defence: the role of metal-binding proteins

Franziska Schurz1, Monica Sabater-Vilar2 and Johanna Fink-Gremmels2*

Department of Analytical and Molecular Pharmacology, TNO Pharma Zeist and 2 Department of Veterinary Pharmacy, Pharmacology and Toxicology, University of Utrecht, The Netherlands

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Oxidative Stress in Autism, Chauhan (PDF)

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Oxidative Stress in Autism, Review (PDF)

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Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism, James et al (PDF)

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Developmental Regression and Mitochondrial Dysfunction in a Child With Autism(PDF)

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Mitochondrial Energy-Deficient Endophenotype in Autism (PDF)

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Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels (PDF)

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Bridging from Cells to Cognition in Autism Pathophysiology: Biological
Pathways to Defective Brain Function and Plasticity
 (PDF)

1Matthew P. Anderson, 2Brian S. Hooker and 3Martha R. Herbert

American Journal of Biochemistry and Biotechnology 4 (2): 167-176, 2008

We review evidence to support a model where the disease process underlying autism may begin when an in utero or early postnatal environmental, infectious, seizure, or autoimmune insult triggers an immune response that increases reactive oxygen species (ROS) production in the brain that leads to DNA damage (nuclear and mitochondrial) and metabolic enzyme blockade and that these inflammatory and oxidative stressors persist beyond early development (with potential further exacerbations), producing ongoing functional consequences.

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Evidence of Mitochondrial Dysfunction in Autism and Implications for Treatment(PDF)

Daniel A. Rossignol, J. Jeffrey Bradstreet

Abstract: Classical mitochondrial diseases occur in a subset of individuals with autism and are usually caused by genetic anomalies or mitochondrial respiratory pathway deficits. However, in many cases of autism, there is evidence of mitochondrial dysfunction (MtD) without the classic features associated with mitochondrial disease. MtD appears to be more common in autism and presents with less severe signs and symptoms. It is not associated with discernable mitochondrial pathology in muscle biopsy specimens despite objective evidence of lowered mitochondrial functioning. Exposure to environmental toxins is the likely etiology for MtD in autism. This dysfunction then contributes to a number of diagnostic symptoms and comorbidities observed in autism including: cognitive impairment, language deficits, abnormal energy metabolism, chronic gastrointestinal problems, abnormalities in fatty acid oxidation, and increased oxidative stress. MtD and oxidative stress may also explain the high male to female ratio found in autism due to increased male vulnerability to these dysfunctions. Biomarkers for mitochondrial dysfunction have been identified, but seem widely under-utilized despite available therapeutic interventions. Nutritional supplementation to decrease oxidative stress along with factors to improve reduced glutathione, as well as hyperbaric oxygen therapy (HBOT) represent supported and rationale approaches. The underlying pathophysiology and autistic symptoms of affected individuals would be expected to either improve or cease worsening once effective treatment for MtD is implemented.

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Mitochondrial delivery is essential for synaptic potentiation.  

Biol Bull. 2007 Apr;212(2):169-75.  Tong JJ

Biophysics and Physiology, University of California, Irvine, CA 92697, USA. tongja@uci.edu

Mitochondria, as portable generators that power synaptic function, regulate the ATP supply and calcium homeostasis in the neuron. As molecular interactions within the synapses before and after the potentiation are beginning to be elucidated, the deciding moment during the tetanic stimulation that gives rise to the strengthening of the synapse remains a mystery. Here, I recorded electrically from an intact Drosophila nervous system, while simultaneously using time-lapse confocal microscopy to visualize mitochondria labeled with green fluorescent protein. I show that tetanic stimulation triggers a fast delivery of mitochondria to the synapse, which facilitates synaptic potentiation. Rotenone, an inhibitor of mitochondrial electron transport chain complex I, suppresses mitochondrial transport and abolishes the potentiation of the synapse. Expression of neurofibromin, which improves mitochondrial ATP synthesis in the neuron, enhances the movements of mitochondria to the synapse and promotes post-tetanic potentiation. These findings provide unprecedented evidence that the mitochondrial delivery to the synapse is critical for cellular learning.

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Mitochondria at the synapse.

Neuroscientist. 2006 Aug;12(4):291-9.

Ly CVVerstreken P

Department of Neuroscience and Molecular and Human Genetics, Howard Hughes Medical Institute Baylor College of Medicine, Houston, TX 77030, USA. cindy.ly@bcm.tmc.edu

Synapses are packed with mitochondria, complex organelles with roles in energy metabolism, cell signaling, and calcium homeostasis. However, the precise mechanisms by which mitochondria influence neurotrans mission remain undefined. In this review, the authors discuss pharmacological and genetic analyses of synaptic mitochondrial function, focusing on their role in Ca2+ buffering and ATP production. Additionally, they will summarize recent data that implicate synaptic mitochondria in the regulation of neurotransmitter release during intense neuronal activity and link these findings to the pathogenesis of neurodegenerative diseases that feature disrupted synaptic mitochondria, including amyotrophic lateral sclerosis and hereditary spastic paraplegia.

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J Child Neurol. 2002 Jun;17(6):435-9.

Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome

Fillano JJ, Goldenthal MJ, Rhodes CH, Marín-García J.
Department of Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA.

A group of 12 children clinically presenting with hypotonia, intractable epilepsy, autism, and developmental delay, who did not fall into previously described categories of mitochondrial encephalomyopathy, were evaluated for mitochondrial respiratory enzyme activity levels, mitochondrial DNA, and mitochondrial structural abnormalities. Reduced levels in specific respiratory activities were found solely in enzymes with subunits encoded by mitochondrial DNA in seven of eight biopsied skeletal muscle specimens evaluated. Five cases exhibited increased levels of large-scale mitochondrial DNA deletions, whereas pathogenic point mutations previously described in association with mitochondrial encephalomyopathies were not found. Mitochondrial structural abnormalities were present in three of four patients examined. Our findings suggest that mitochondrial dysfunction, including extensive abnormalities in specific enzyme activities, mitochondrial structure, and mitochondrial DNA integrity, may be present in children with a clinical constellation including hypotonia, epileptic seizures, autism, and developmental delay. The acronym HEADD is presented here to facilitate pursuit of mitochondrial defects in patients with this clinical constellation after other causes have been excluded.

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Histol Histopathol. 2005 Jul;20(3):957-67.

Role of oxidative damage in the pathogenesis of viral infections of the nervous system.

Valyi-Nagy T, Dermody TS.
Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.

Oxidative stress, primarily due to increased generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), is a feature of many viral infections. ROS and RNS modulate the permissiveness of cells to viral replication, regulate host inflammatory and immune responses, and cause oxidative damage to both host tissue and progeny virus. The lipid-rich nervous system is particularly susceptible to lipid peroxidation, an autocatalytic process that damages lipid-containing structures and yields reactive by-products, which can covalently modify and damage cellular macromolecules. Oxidative injury is a component of acute encephalitis caused by herpes simplex virus type 1 and reovirus, neurodegenerative disease caused by human immunodeficiency virus and murine leukemia virus, and subacute sclerosing panencephalitis caused by measles virus. The extent to which oxidative damage plays a beneficial role for the host by limiting viral replication is largely unknown. An enhanced understanding of the role of oxidative damage in viral infections of the nervous system may lead to therapeutic strategies to reduce tissue damage during viral infection without impeding the host antiviral response.

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Mitochondria and neuronal activity (PDF)

Oliver Kann and Richard Kovács

Am J Physiol Cell Physiol 292:641-657, 2007. First published Nov 8, 2006; doi:10.1152/ajpcell.00222.2006

Mitochondria are central for various cellular processes that include ATP production, intracellular Ca2 signaling, and generation of reactive oxygen species. Neurons critically depend on mitochondrial function to establish membrane excitability and to execute the complex processes of neurotransmission and plasticity. While much information about mitochondrial properties is available from studies on isolated mitochondria and dissociated cell cultures, less is known about mitochondrial function in intact neurons in brain tissue. However, a detailed description of the interactions between mitochondrial function, energy metabolism, and neuronal activity is crucial for the understanding of the complex physiological behavior of neurons, as well as the pathophysiology of various neurological diseases. The combination of new fluorescence imaging techniques, electrophysiology, and brain slice preparations provides a powerful tool to study mitochondrial function during neuronal activity, with high spatiotemporal resolution. This review summarizes recent findings on mitochondrial Ca2 transport, mitochondrial membrane potential (m), and energy metabolism during neuronal activity. We will first discuss interactions of these parameters for experimental stimulation conditions that can be related to the physiological range. We will then describe how mitochondrial and metabolic dysfunction develops during pathological neuronal activity, focusing on temporal lobe epilepsy and its experimental models. The aim is to illustrate that 1) the structure of the mitochondrial compartment is highly dynamic in neurons, 2) there is a fine-tuned coupling between neuronal activity and mitochondrial function, and 3) mitochondria are of central importance for the complex behavior of neurons.

Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis

Logo for mitochondrial DNA

Introduction 

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impaired social interaction and communication, as well as isolated interests and repetitive or stereotyped behaviors [1]. ASDs pose a significant burden to affected individuals, their families and society. This burden comes both from the debilitating and lifelong nature of ASDs and from their prevalence. It is now estimated that about one out of every 166 children is affected with ASD [2]. Most cases are idiopathic, although there are many uncommon or rare genetic and metabolic causes of autism that are increasingly recognized [3]–[5].

In 1998, Lombard postulated mitochondrial dysfunction as a cause of autism [6]. Prior and subsequent case reports provided biochemical data indicating perturbation of mitochondrial energy metabolism in some individuals with ASD [7]–[12], including mtDNA mutations in several [10], [13], [14]. Recently, Oliveira and colleagues published a population-based survey of school-age children with ASD. They found that 7% of those who were fully tested met criteria for definite mitochondrial respiratory chain disorders and were also clinically indistinguishable from other children with ASD [15]. This work is notable because it suggests that mitochondrial disorders of energy production may be present in a substantial percentage of children with ASD. To better describe the clinical spectrum of children with ‘mitochondrial autism’, we undertook a chart review of the biochemical, genetic, and histopathological findings in 25 patients with ASD who had unequivocal evidence of a disorder of oxidative phosphorylation.

via PLoS ONE: Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis.

Just say NO to EDTA

 

There are many Docs out there who still use EDTA to chelate autistic children.  If you find yourself with a doctor who is recommending this type of chelation you should certainly run in the other direction.

There are many different methods of chelation being promoted today and we must be vigilant in choosing what is safe for our children.

There is a lot of hype in the media about the dangers of chelation therapy.  They regularly accuse chelation as dangerous, saying it has killed one child already.  They are correct.  IV EDTA has in fact killed a child.  A young boy died tragically and unnecessarily by improper use of a form of EDTA.

EDTA binds to other needed minerals as well as to heavy metals depleting the body of necessary nutrients.  What happened to this boy was a tragedy as the wrong medicine was administered.  CaEDTA is EDTA bound with calcium so that when it is administered it doesn’t deplete the bodies calcium levels. This boy was mistakenly given sodium EDTA instead of CaEDTA.  It was given in a high dose through and IV and the rapid excretion of Calcium caused him to suffer a cardiac arrest and die.  We feel very sad for this family just as we feel sad for the many children who have been injured by iatrogenic (doctor caused) means.

Unfortunately the negatives of EDTA do not stop by simply using the correct med (caEDTA) as those chelation docs would suggest.  There is a second insult which this medicine causes in our children.  Research by Boyd Haley has demonstrated that when used in the presence of mercury toxicity the EDTA binds with the mercury forming HgEDTA.  This substance has been shown to interact with brain tubulin (a neuroprotein) and increases the damage caused by mercury.

While EDTA is an effective treatment for cardiovascular plaques and is effective at removing lead, it should not be used in Autistic children (DMSA is an alternative chelator of lead and can be safely used orally).  For cardiovascluar patients who wish to pursue EDTA treatment it should only be used when preceded by safe mercury detox (using ALA) to clear mercury from fatty tissues including the brain.

 

haley_study_edta_and_mercury

 

 

 

Reduced levels of mercury in first baby haircuts of autistic children

Reported rates of autism have increased sharply in the United States and the United Kingdom. One possible factor underlying these increases is increased exposure to mercury through thimerosal-containing vaccines, but vaccine exposures need to be evaluated in the context of cumulative exposures during gestation and early infancy.

Differential rates of postnatal mercury elimination may explain why similar gestational and infant exposures produce variable neurological effects. First baby haircut samples were obtained from 94 children diagnosed with autism using Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) criteria and 45 age- and gender-matched controls. Information on diet, dental amalgam fillings, vaccine history, Rho D immunoglobulin administration, and autism symptom severity was collected through a maternal survey questionnaire and clinical observation.

Hair mercury levels in the autistic group were 0.47 ppm versus 3.63 ppm in controls, a significant difference. The mothers in the autistic group had significantly higher levels of mercury exposure through Rho D immunoglobulin injections and amalgam fillings than control mothers. Within the autistic group, hair mercury levels varied significantly across mildly, moderately, and severely autistic children, with mean group levels of 0.79, 0.46, and 0.21 ppm, respectively.

Hair mercury levels among controls were significantly correlated with the number of the mothers’ amalgam fillings and their fish consumption as well as exposure to mercury through childhood vaccines, correlations that were absent in the autistic group.

Hair excretion patterns among autistic infants were significantly reduced relative to control.

These data cast doubt on the efficacy of traditional hair analysis as a measure of total mercury exposure in a subset of the population.In light of the biological plausibility of mercury’s role in neurodevelopmental disorders, the present study provides further insight into one possible mechanism by which early mercury exposures could increase the risk of autism.

via Reduced levels of mercury in first bab… [Int J Toxicol. 2003 Jul-Aug] – PubMed – NCBI.

Mercury concentration in ambient air and the risk of autism

Appollo Beach power plant 01432

Ecologic studies of the spatial relationship between disease and sources of environmental contamination can help to ascertain the degree of risk to populations from contamination and to inform legislation to ameliorate the risk.

Population risks associated with persistent low-level mercury exposure have recently begun to be of concern and current reports implicate environmental mercury as a potential contributor in the etiology of various developmental and neurodegenerative diseases including autism and Alzheimer’s disease.

In this demonstration of preliminary findings, we demonstrate for Bexar County Texas and Santa Clara County California, the hypothesis that the spatial structure of the occurrence of autism has a positive co-variation with the spatial structure of the distribution of mercury in ambient air.

The relative risk of autism is greater in the geographic areas of higher levels of ambient mercury.

We find that the higher levels of ambient mercury are geographically associated with point sources of mercury emission, such as coal-fired power plants and cement plants with coal-fired kilns. Although this does not indicate a cause, these results should not be dismissed, but rather seen as a preliminary step for generating a hypothesis for further investigation.

via The value of ecologic studies: mercury co… [Rev Environ Health. 2011] – PubMed – NCBI.

Ancestry of pink disease (caused by mercury) identified as a risk factor for autism spectrum disorders.

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. Autism spectrum 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.

via Ancestry of pink disease (infanti… [J Toxicol Environ Health A. 2011] – PubMed – NCBI.

Did Acetaminophen Provoke the Autism Epidemic?

tylenol bottle closeup

http://www.altmedrev.com/publications/14/4/364.pdf

I was invited to view a webinar on a possible connection between Autism and Acetaminophen some months ago.  When I was first told about the next great claim of a definitive cause for Autism, I was skeptical.  I had listened to so many debates on causation and autism.  Honestly, after awhile, the obvious politics involved becomes very tiresome.

I voiced my skepticism, but as this mother proceeded to describe some of the accusations against Acetaminophen (Tylenol), I started to listen more closely.  That is when it hit me.  Unlike all the other causation theories, this could actually explain my child’s Autism and his remarkable improvement through chelation.

You see, my son did not match the typical case histories of othAcetaminophen and Autismer Autistic children.  In fact, I almost failed to pursue biomedical treatments because he did not have a typical story.

My child did not regress.  He never developed normally.  After his diagnosis it became apparent that he was born with Autism.

My child did not have any health problems or frequent ear infections.  In fact the only ear infection and subsequent round of antibiotics he had ever had was at 2.2 years of age, well after his Autism was apparent.

My child was never vaccinated.  I did not receive any vaccines or Rhogam while pregnant.

This was my 5th child.  If his Autism was solely due to my toxic body burden one would expect my previous children to be more affected.

We did not move.  My 3rd child and 4th child were both born and raised in the exact same apartment building as my 5th child.  The environment hadn’t changed.

I really was at a loss and none of the typical biomed explanations quite fit our experience.  Still biomed advocates were proposing using natural safe approaches, like diet modification along with vitamins and other supplements.  These weren’t things that could damage my child, so I really had no reason not to at least give it a go.

We did the GFCF diet and saw improvement.  We did yeast treatments and gut supports, and saw improvement.  He improved on zinc.  He improved on B6.  He improved with almost every intervention we tried.

Then we found AC chelation and he improved to point that most would consider him recovered.  He is in a typical school with typical peers with no supports.  He has friends and has been invited to parties.  In fact, at the end of this year they tested him for the gifted program and determined that he was academically gifted and will start going to an enrichment school one day a week because his typical classroom isn’t quite academically challenging enough.  He is flourishing.  (He does still have some precocious speech and slightly odd gestures but no sign  of Autism.  He was diagnosed with low functioning Autism at age 2.5).

With that kind of drastic improvement with chelation protocol, it was apparent he was metal toxic.  But how?  By now the how didn’t matter much to me.  We left the how question alone to dangle in the wind as we had found the solution, so it didn’t seem important to figure out exactly how the problem started or what the cause could have been.

Never the less the question always dangled, it never totally disappeared from our minds.

Insert the Acetaminophen theory.

You know what was different about my 5th child’s med history?  I was over due and very uncomfortable during my last trimester.  It was so bad that I could not even get two full hours of sleep per night.  I was miserable and exhausted.  My midwife was concerned about whether I would have the energy to mount a proper labor and delivery.  I asked her if there was anything safe I could take while pregnant to help me sleep.  ( I just knew her answer would be no).  She said yes and came back with an Rx for Tylenol 3 with codeine.

I told her I thought it was over kill, “I am uncomfortable but I am not in pain.  I just need some sleep.”

She said that it didn’t cross the placental wall and that although I didn’t need the pain relief, it was the only thing they could give me that was safe for my baby.

I took Tylenol 3 almost every night for 2 weeks.

Quote from article:

Acetaminophen taken during pregnancy may provoke autism present at birth…

Finally, a possible explanation for what we had experienced.  The Tylenol I took may have interfered with his ability to detox environmental toxins as well as impaired his brain function and immune system.  The toxins his body built up could be responsible for the rest.  Is this truth or theory?

At this point it is only theory.  But it is the first theory that had a chance of explaining what we saw, and the research is convincing.  It is solid enough that I would never give Tylenol to another child.  I would recommend all children and pregnant mothers avoid Tylenol and other acetaminophen containing products.  Until more research is done it only makes sense to be cautious.

Mercury Toxicity: What to do about it.

In the book Amalgam Illness by Andrew Hall Cutler the author has an excellent explanation on why ALA chelation is the only safe, effective means to remove mercury from the Brain and CNS.

In short: metalic mercury, organic mercury, methylmercury and ethylmercury are all processes by the body and can then be transformed into inorganic mercury.

When this happens in the brain and CNS the inorganic mercury is trapped.  The body has no mechanism for getting it out past the Blood Brain Barrier.

Alpha Lipoic Acid is the only safe and effective chelator that we currently have available to us which can cross the blood brain barrier and remove inorganic mercury from the brain.

Mercury has the potential to cause many of the same behavioral symptoms seen in children with Autsim.  If mercury is the root cause for the behavior and physical symptoms the person is suffering from, then appropriate, safe chelation has the potential to recover the person from the ailments they are experiencing.

In my opinion since ALA is a wonderful Antioxident when not in the presance of heavy metals and has the potential to offer relief if the symptoms are caused by metals it only makes sense to give it a whirl.  See Safe Chelation for details.

ATSDR – Public Health Statement: Mercury.

At the above link you will find information on the following:

1.1 What is mercury?

1.2 What happens to mercury when it enters the environment?

1.3 How might I be exposed to mercury?

1.4 How can mercury enter and leave my body?

1.5 How can mercury affect my health?

1.6 How can mercury affect children?

1.7 How can families reduce the risk of exposure to mercury?

1.8 Is there a medical test to determine whether I have been exposed to mercury?

1.9 What recommendations has the federal government made to protect human health?

References

Where can I get more information?

Lead Toxicity: Where Is Lead Found?

Summary: Where Is Lead Found?

Lead Source Contaminated Media

Lead solder/pipes

Drinking water

Packages or storage containers

Food, beverages

Paint (pre-1978)

Household dust and soil

Production sources

Imported foods, remedies, cosmetics, jewelry

Mining and smelting

Outdoor air and dust

Workplaces involving lead

Outdoor and indoor air and dust

Gasoline (pre-1988)

Soil

via Lead (Pb) Toxicity: Where Is Lead Found? | ATSDR – Environmental Medicine & Environmental Health Education – CSEM.

Follow the link above for the full article as well as a very good printable resource on sources of lead toxicity.

Tip:  Since calcium apposes leads absorption and storage (especially bone stores) getting adequate calcium is especially important for growing children.  Raw milk, cheese, and yogurt as well as quality calcium supplements and bone broths are excellent sources of calcium.

ADHD Outcomes: Being Rejected Can Have a Bigger Impact than Having Friends

This is one of the reasons that we chose to keep him back a year.  I would have continued to homeschool him except that at 6 years old he was playing well,  fitting in with peers, and making friends.

I know that everyone has to make an individual choice based on what is best for their child and their family so don’t think I am judging the choices of others here.  But I would not have sent my son to a regular classroom if he needed an aid.  I would much prefer him to be in an Autism class/school.

My biggest concern regarding school choice was self-esteem.  I was confident we could teach the academics in fact his reading and computation skills were well above age appropriate levels, but I wanted him to be socially ready to benefit from school and not fell less than the other children.  He has done very well this year he turned a bully into a friend and dealt with a schoolboy crush (he found his future bride as he very much liked the sound of her voice).

 

ADHD Outcomes – Child Psychology and Parenting Blog: Child-Psych.org.

As with any childhood disorder, we want to know what can protect the child from long-term negative outcomes.  When it comes to ADHD, studies demonstrate all sorts of long-term problems that we would rather prevent, such as delinquency, depression, and anxiety.

As I mentioned in a recent editorial, data from the Multimodal Treatment Study of ADHD (MTA) revealed some surprising results about long-term outcomes for children with ADHD.  Among the results include a finding that what we typically do to treat ADHD (medication and/or psychosocial treatment) does not significantly improve peer problems.  And long-term peer difficulties can lead to a host of externalizing and internalizing problems that can last into the adult years.

A recent study published in the Journal of Abnormal Child Psychology looked at two different areas of peer relationships in children with ADHD: peer rejection and friendship.  The authors predicted that children with ADHD that were rejected by peers and did not have friends would suffer poorer outcomes in adolescence.  They further predicted that having friends would help lessen the impact of peer rejection and thereby lead to better outcomes.  Their results revealed a surprising finding: friendships did not have the protective impact that they thought they would find.

The Relationships of Glutamine, Glutamate, and Glutathione Diet for Amyotrophic Lateral Sclerosis

B0007691 Amino acid: Cysteine

B0007691 Amino acid: Cysteine (Photo credit: wellcome images)

There is a lot of talk in the Autism community about Supplementing Glutethione.  This article does a great job presenting some of reasons not to.

We should also remember that an estimated 30%-50% of mercury toxic people are high cysteine and therfore supplementing with NAC is a no go for them.

NAC is a sulfur compound as such it is a monothiol meaning it has only 1/2 a claw so to speak.  When cysteine is in abundance it will “ping” mercury all over the place without actually removing it from the body.

While chelating we should aim at keeping supplemental NAC below 200 mg daily and increase sulfur foods for low cysteine kids.

For high cysteine kids we should avoid NAC and restrict sulfur foods.  To increase glutethione we can give glutamate and glycine in a 2:1 ratio.

Of course the best thing we can do to increase glutethione is to give vitamin C at least 4 times throughout the day as it will regenerate glutethione.

The Relationships of Glutamine, Glutamate, and Glutathione Diet for Amyotrophic Lateral Sclerosis.

Glutathione is made from the amino acids L-cysteine + L-glutamate + glycine. The glutathione the body needs is manufactured in the liver. Much ado is made about supplementing glutathione to counteract the oxidative reactions in the brain occurring in ALS, MS and more. But there are problems with supplementation of glutathione or its precursors. Consider these factors:

When the body has excess nitric oxide it converts to peroxynitrite and this reacts with glutathione to make s-nitrosglutathione (a molecule involved in inflammation and vasodilatation).

Since glutathione is poorly absorbed from the intestines into the blood (and this may be worse in people who have physiological problems, preventing it from doing so), taking the precursors glutamine or N-acetylcysteine in an attempt to manufacture glutathione can backfire. In fact, people working with autistic children have found that the children do not do well on supplemental NAC or glutamine. Migraneurs (known nitric oxide excess leading to excessive vasodilatation and inflammation) will find that intravenous glutathione will cause a migraine of the worst sort (see #1).

CEHC develops list of ten chemicals that contribute to autism, learning disabilities | The Autism News

Reports of autism cases per 1,000 children gre...

Reports of autism cases per 1,000 children. (Photo credit: Wikipedia)

Current science recognizes the fallacy in the theory of macro-evolution.  You will not find it touted as fact in academic circles the way you do in public primary schools and even in the media.

Similarly science is finding the connection between Autism Spectrum Disorders  (and other developmental delays) and environmental assaults like heavy metals.  The debate connecting heavy metal toxicity and Autism is ongoing, not because of lack of research, but because of politics.

Children’s Environmental Health Center (CEHC) at Mount Sinai School of Medicine developed the list of ten chemicals found in consumer products that are suspected to contribute to autism and learning disabilities to guide a research strategy to discover potentially preventable environmental causes. The top ten chemicals are:

1.Lead

2.Methylmercury

3.PCBs

4.Organophosphate pesticides

5.Organochlorine pesticides

6.Endocrine disruptors

7.Automotive exhaust

8.Polycyclic aromatic hydrocarbons

9.Brominated flame retardants

10.Perfluorinated compounds

via CEHC develops list of ten chemicals that contribute to autism, learning disabilities | The Autism News.