Excerpt:
“In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.”
Excerpts:
“In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism.”
Exerpt
“These findings concur with mounting data suggesting that environmentally mediated effects on the epigenome may be relatively common and important for disease.”
Excerpts:
“GST [Glutathione S-transferase] is a metabolic biomarker directly associated with ASD. The human gene product for GST constitutes a candidate susceptibility protein due to its tissue distribution and role in oxidative stress and methionine metabolism, which results in neuronal injury and death.”
“Results of a recent study further demonstrated that glutathione, total glutathione and activity levels of GST were significantly lower in autistic patients as compared with control subjects; however, homocysteine, thioredoxin reductase and perioxidoxin levels were remarkably higher.”
“Autistic children with metabolic disturbances are known to display reduced metabolic activities of GST, cysteine, glutathione and methionine, which are associated with methionine transmethylation and trans-sulfation.”
Excerpts:
“Intramuscular injection of alum-containing vaccine was associated with the appearance of aluminum deposits in distant organs, such as spleen and brain where they were still detected one year after injection.”
“Cerebral translocation was not observed after direct intravenous injection, but significantly increased in mice with chronically altered blood-brain-barrier.”
Conclusion
Nanomaterials can be transported by monocyte-lineage cells to DLNs, blood and spleen, and, similarly to HIV, may use CCL2-dependent mechanisms to penetrate the brain. This occurs at a very low rate in normal conditions explaining good overall tolerance of alum despite its strong neurotoxic potential. However, continuously escalating doses of this poorly biodegradable adjuvant in the population may become insidiously unsafe, especially in the case of overimmunization or immature/altered blood brain barrier or high constitutive CCL-2 production.
PLoS ONE 8(3): e58058. doi:10.1371/journal.pone.0058058 Identification of Unique Gene Expression Profile in Children with Regressive Autism Spectrum Disorder (ASD) and Ileocolitis Walker SJ, Fortunato J, Gonzalez LG, Krigsman A AbstractGastrointestinal symptoms are common in children with autism spectrum disorder (ASD) and are often associated with mucosal inflammatory infiltrates of the...
Excerpt:
“Increasing maternal CRP levels, classified as a continuous variable, were significantly associated with autism in offspring. For maternal CRP levels in the highest quintile, compared with the lowest quintile, there was a significant, 43% elevated risk. This finding suggests that maternal inflammation may have a significant role in autism, with possible implications for identifying preventive strategies and pathogenic mechanisms in autism and other neurodevelopmental disorders.”
Excerpts:
“In our clinical work and review of the literature, we have been impressed by the possible role of autoimmune disorders as influencing the pathophysiology of a distinct, objectively defined etiologic subtype of ASDs.”
“The notion that environmental factors contribute to ASD prevalence continues to evolve. Once-influential theories suggesting links among exposure to vaccines containing attenuated virus or toxins, conditions such as inflammatory bowel disease, and ASDs have fallen from favor since the retraction of a key study (Wakefield et al, 1998). It is important to emphasize, however, that the major reason for retraction was poor scientific method rather than theoretical flaws. Although ASDs are currently within the realm of psychiatrists and neurologists, it is becoming clear that at least some subtypes represent whole-body disorders, offering exciting new possibilities for therapy.”
Excerpt:
“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.”
Abstract
Autism spectrum disorders (ASD) are neurodevelopmental diseases that affect an alarming number of individuals. The etiological basis of ASD is unclear, and evidence suggests it involves both genetic and environmental factors. There are many reports of cytokine imbalances in ASD. These imbalances could have a pathogenic role, or they may be markers of underlying genetic and environmental influences. Cytokines act primarily as mediators of immunological activity, but they also have significant interactions with the nervous system. They participate in normal neural development and function, and inappropriate activity can have a variety of neurological implications. It is therefore possible that cytokine dysregulation contributes directly to neural dysfunction in ASD. Further, cytokine profiles change dramatically in the face of infection, disease, and toxic exposures. Therefore, imbalances may represent an immune response to environmental contributors to ASD. The following review is presented in two main parts. First, we discuss select cytokines implicated in ASD, including IL-1Β, IL-6, IL-4, IFN-γ, and TGF-Β, and focus on their role in the nervous system. Second, we explore several neurotoxic environmental factors that may be involved in the disorders, and focus on their immunological impacts. This review represents an emerging model that recognizes the importance of both genetic and environmental factors in ASD etiology. We propose that the immune system provides critical clues regarding the nature of the gene by environment interactions that underlie ASD pathophysiology.
Abstract
Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.
