Dr. Wakefield Sues Brian Deer and BMJ's Fiona Godlee
That’s My Boy!

The Inflammation Highway: aka Autism

  Tummy-ache-abdominal-pain-t13513By Lisa Goes

"The one thing about my husband and I...we laugh...A lot. We find a way. We really do. Poop filled sleepless nights, injuries, missed appointments, clutter everywhere, missing paperwork...sometimes all you can do is laugh. But today, looking at the dark circles we've seen so many times under our children's eyes, seeing the suffering, the real genuine human suffering that we have worked for three years to alleviate...to see it reach these depths...there is no laughing today. There is sadness. Even the fight is gone. I should be sleeping, but I have to read up on one of our new remedies. Maybe this will be the one that touches his immune damage and regulates him? Maybe. Maybe, it will work for him like it has for THOUSANDS of other children. Maybe. I can't sleep when this could be it and I could be calling the next doctor tomorrow and we could have one less day of this. Plus, I already have an appointment to see a doctor tomorrow and I will need him to know that I know what I'm talking about. If there is one thing you learn as an autism parent it is that YOU MUST KNOW WHAT YOU ARE TALKING ABOUT WITH DOCTORS. You must learn to speak their language. If you don't you will get dismissed. Must read, now.

But, before I go, just need to let everyone know the women who work for us are angels from God. They were hurt today. Two of them. In their sweetest voices they kept repeating, "nice hands." And "time to get down monkey" when he climbed on the counter for the 27th time on their shift. He is 50 lbs now. Very fast and very strong. They get him. They see the real Noah in there, fighting like hell. He is mad. In fact, that's what he said in therapy today, "I'm MAD!" His therapists were thrilled. They were so excited to see him emote appropriately. I agree with them, it's encouraging. It's just that, he's mad he's sick. He's mad his head hurts all the time. He's mad his three year old brother can use the toliet and he cannot. He's mad that his body is rebelling against him and everything hurts. He's mad that in addition to not getting to go where everyone else goes and doing all the fun things other 5 year olds do, he also cannot EAT anything they do. It seems cruel doesn't it? It is.

Autism is the cruelest most malicious, devious, conniving, heinous disease. If you fear the chicken pox or diarrhea more you are in big, big trouble. Because I guarantee with the new schedule autism will come a knocking at your door. And it will get in. It finds a way. Sometimes it looks like OCD, sometimes it looks like ADHD, even arthritis. "That's nuts!", you say. Not really. It should all just be called autism. Because any time pharma causes inflammation they don't want you to find out about, they just make up a word for it. Autism. Asthma. ADD. Just made up words for inflammation. Off to read ABOUT AUTISM . It's a good one, you might want to check it out yourself... Much hope for all our beautiful children. xo lj "

Lisa Goes is Contributing Editor to Age of Autism.



Note this speaks about gene expression. There are other interesting points in the report I have not quoted. {reference to gliadin is one}

Streptococcal infection-related autoimmunity and autism: crosstalk in protein functional networks

Genes of note
"Many ASD-associated genes are particularly expressed and associated within the IS include, APP, BCL11A, KLC1, ETS1, MET, IL1RN, NDRG1, NGF, TNF and VEGF (Table 5). These genes are receptors (APP, MET, IL1RN), involved in angiogenesis (NDRG1, VEGF), cell maintenance and development (BCL11A, KLC1, NGF,) and inflammation (ETS1, TNF). APP, ETS1, TNF and VEGF may be of a particular interest. APP encodes for the amyloid beta precursor protein, which is highly expressed in neurons and glial cells [49-51]. However, APP products also have a functional role, including synaptic adhesion, neuroprotective properties and antimicrobial functions [52-54]. APP transport in the brain is mediated by subunits formed by KLC1 molecules [55]. ETS1 encodes for ETS proto-oncogene 1, a transcription factor that has roles in inflammation and chemokine and cytokine activation particularly in endothelial cells and links to reactive microglia [56,57]. ETS-1 has been shown to co-localise with VEGF, TNF and APP products in the brain [57]. Vascular endothelial growth factors (VEGF) are a family associated with endothelial cell regulation and angiogenesis, even influencing the blood-brain barrier (BBB) [58,59]. Notably, VEGF appears to be able to alter the permeability of the BBB, and can increase permeability and cause breakdown [59-61]. Tumour necrosis factor (TNF) is a proinflammatory cytokine and is implicated in numerous functions and pathologies. TNF is implicated in inflammation and can affect the permeability of the BBB [62]. Of the streptococcal-associated genes, autoantibody targets MAG and MBP are the most prominent. MAG encodes for myelin-associated glycoprotein, a membrane protein that inhibits nerve regeneration [63]. MBP encodes for myelin basic protein, which is a major protein of the myelin sheath and has a regulatory role in myelination [64].

Potential mechanism

Our vision of how streptococcal infections can cause ASD in children is presented in Figure 7. Alterations in ETS1, TNF or VEGF functions, or their combination can decrease the permeability of the BBB and leave an individual vulnerable to toxic or autoimmune components developed due to an infection. Mutations may not act directly upon these genes but may affect their expression and protein proliferation [65,66]. This may be a result of mutations in promoter regions or polymorphisms in cytokines (TNF) or may be an upstream molecule [67-69]. VEGF and ETS1 have been associated with TNF in Alzheimer’s disease [57]; therefore, we can conceive that they work functionally together in the brain. ETS1 and VEGF can induce microglial activity towards increased TNF production [57,70-72]. Additionally VEGF expression in astrocytes, a component of the BBB, can induce the BBB breakdown [73], supported by a streptococcal- induced inflammation. Streptococcal infections produce autoantibodies against MAG and MBP. With a weakened BBB, anti-MAG and anti-MBP can travel across and target developing neurones for destruction by immune cells able to cross the weakened BBB. In fact, thinner myelination has been reported in some areas of the brain in ASD, such as the orbitofrontal cortex (OFC), as well as a high density of thinly myelinated neurons when compared to controls [74]. OFC abnormalities have already been associated with ASD and it is speculated that a decrease in myelin may mean that longer axons that provide the cross talk for emotion-based behaviors are less efficient [75,76]. From the other hand, neurite overgrowth found in ASD patients [77,78] may be explained by MAG (inhibitor of neurite regrowth) immuno- inhibition."


From published and our study it is clear that there is overlap within the IS and NS functions that may be responsible for synergism in inheritable and environmental components in aetiology of a number of neuro-psychiatric disorder, and ASD, in particular. APP, BCL11A, KLC1, ETS1, MET, IL1RN, NDRG1, NGF, TNF, VEGF, HSPD1, MAG and MBP proteins are likely candidates to affect susceptibility to the environmental component. What is notable is that many of these genes were identified to have roles in the developing brain, reflecting the paediatric nature. Despite a proposed theory (Figure 7), uncertainties remain as to how some of these genes may interact to affect ASD. We suggest that APP, HSPD1, MET and NDRG1 may be implicated in the reaction caused by the autoantibodies. Those would be ideal candidates to investigate further using experimental methods in animal models or to be tested for in cases of PANDAS or more profound ASD cases in children."



A personal correction I have long ignored. I don't know if any have see a holistic connection of all the things I have posted though a couple of associations I posed never panned out. Yet, I posted one clear error and only have my indiscretion to thank for doing so.

This association did prove fruitful, but not via the gene I listed as a description. I posted this:

"Transforming growth factor beta-1 enhances Smad transcriptional activity through activation of p8 gene expression.


I then listed this which is not associated .
TRP-P8 Gene Card

It is rather elucidated through these reports.

Transforming growth factor beta-1 enhances Smad transcriptional activity through activation of p8 gene expression.


and this:

The human NUPR1/P8 gene is transcriptionally activated by transforming growth factor β via the SMAD signaling pathway.


and possibly this:

NUPR1 interacts with p53, transcriptionally regulates p21 and rescues breast epithelial cells from doxorubicin-induced genotoxic stress.


P53 is a player.

Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother

"The results of the SNP arrays were confirmed by qPCR (Figure 2b). In patients 2 and 3, the qPCR confirmed the duplication of VWA3A located at 16p12.1, and NUPR1, LAT, and ALDOA located at 16p11.2, with normal dosage of the genes flanking the rearranged region. In patient 1 and the father, both NUPR1 and LAT were deleted."

"Of the other eight genes contained in the minimal deleted region, three are involved in autosomal recessive disorders (TUFM, ATP2A, CD19), three are involved in immunity (NFATC2IP, LAT, ATXN2L), RABEP2 has a role in membrane trafficking, and little is known about the function of SPNS1 (Supplementary Table 4). SH2B1 haploinsufficiency, already implicated in central nervous system-mediated obesity,24 could also participate in neurodevelopmental and other phenotypes. The widely expressed scaffold protein SH2B1 binds to a variety of ligand-activated receptor tyrosine kinases, including the receptors for nerve growth factor, insulin and insulin-growth factor 1. SH2B1 facilitates glial-cell-line-derived neurotrophic factor-induced neurite outgrowth through RET receptor signaling.28 Through its implication in the RET-glial-cell-line-derived neurotrophic factor signaling pathway, SH2B1 could also have a role in the abnormalities of renal morphogenesis and enteric innervation seen in patients with distal 16p11.2 deletions.26"


I don't think this will matter to most, but I wanted to set it straight.


Just a bit on mir-155. Many others mir's have their part, but this one is particularly involved. It is a inflammatory mediator. When I found it effected the blood brain barrier the other things I had learned about mad a lot more sense. A lot to learned from the reports in the sidebar, pls reading all of these two reports.

miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction


"Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR-155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS-induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia-like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development."


microRNAs as novel regulators of angiogenesis

"As mentioned before, numerous factors are implicated in vessel growth. Among these factors, angiotensin II (Ang II), the main effector peptide of the renin-angiotensin system, appears to be implicated in the regulation of the angiogenic process92. ANG II has been shown to work through both type 1 (AT1R) and type 2 (AT2R) receptors, which display opposing vasomotor and angiogenic actions93. AT1R receptor activation is known to stimulate vascular growth and microvascular angiogenesis in nonneural tissues such as skeletal and cardiac muscle, whereas AT2R activation was recently shown to antagonize these actions94. miR-155 is expressed in ECs and VSMC20,95 and has been shown to specifically interacts with the 3′UTR of the human AT1R mRNA, thereby reducing the endogenous expression of the hAT1R and consequently Ang II signaling95. Translational repression by miR-155 provides yet another mechanism by which AT1R expression can be modulated. In this regard, it has been reported that Ang II induces in a dose dependent manner the expression VEGFR2 and significantly enhances VEGF-induced cell proliferation and tube formation, mediated by AT1 receptor96 and suggesting that AT1 receptor may contribute to the development of diabetic retinopathy by enhancing VEGF-induced angiogenic activity. Then, the downregulation of AT1R by miR-155 suggest an antiangiogenic function for this miRNA in ECs. However, its role in EC angiogenesis has not been specifically addressed. Stimulation of human fibroblast with transforming growth factor β-1 (TGF-β1) decreased the expression of miR-155 and increased the expression of hAT1R. Furthermore, miR-155 is induced in macrophages by cytokines such as tumor necrosis factor α (TNF α) and interferon β (IFNβ)97. Interestingly, angiogenic stimulation of EC with VEGF increases the expression of miR-15520 suggesting VEGF may control the levels of ATR1 via miR-155. Nevertheless, the oncogenic potential of miR-155 has been confirmed in mice, where its overproduction leads to spontaneous B-cell malignancy, showing the complexity of miRNA-mediated regulation, given that the same miRNA may have opposite effects in different biological contexts."



God is Love. Jesus is Lord.


For my satisfaction. Scientific reports will never approach what I have experienced and understood, so screw it. Proof 80 percent.


Having a retro phase after mentioning methionine two posts back. The research that followed led information about these matters as succinctly put on 2005 in the link below. I need to keep these things in mind. Many of you know this I am sure.

The Glutathione/Sulfation/Methylation Pathway



Since there are various routes to Autism this stands out as a curious possible connection to Hep B. I included the first report in an entry in this forum in 2013. The increased expression of Foxp1 in those with Autism in the second study makes the first report's reference to different hep b vaccine responses associate with the Foxp1 in those with Autism I don't know by what mechanisms there would be interaction except through B cell effects. Mutations of Foxp1 are associated with low numbers of Autism and high expression is found in many with Autism. I will try to see if there is a connection, but maybe someone else may know something.

New genetic associations detected in a host response study to hepatitis B vaccine.


This report is best fully read.

Increased gene expression of FOXP1 in patients with autism spectrum disorders

"The FOXP1 gene encodes a member of the forkhead box transcription factor family that contains a DNA-binding domain and a protein-protein interaction domain. The FOXP1 gene functions as a transcription repressor [39, 41, 42], and is widely expressed in the developing and mature brain. The gene has been suggested to be involved in the development and function of the brain [41, 43]. In the literature, three subjects with mental retardation and significant language and speech deficits were detected to have heterozygous deletions overlapping the FOXP1 gene [44]. Two mentally retarded individuals with autistic features were detected to have a de novo intergenic deletion and a de novo nonsense mutation in the FOXP1 gene, respectively [45]. In an exome sequencing study of 20 sporadic ASD patients (simplex ASD), a de novo single-base insertion in FOXP1 that introduces a frameshift and a premature stop codon was identified in a severely affected patient [46]. These data suggest that haploinsufficiency or hypomorphic mutations of FOXP1 with reduced expression or deficient activity of FOXP1 are associated with syndromic or non-syndromic ASD. However, these FOXP1 mutations associated with ASD are rare; they may not apply to the pathogenesis of autism in general. In the present study, we found that increased FOXP1 gene expression was associated with autism in general. Our finding may expand our understanding about the relationship of FOXP1 with autism.

FOXP1 protein was known to interact with another subfamily member FOXP2 to form a heterodimer and co-expressed with FOXP2 in several brain regions, suggesting close functional collaboration between the two proteins [39, 40]. Contactin-associated protein-like 2 (CNTNAP2), a neurexin family protein that functions as a neuronal adhesion molecule and receptor, was found to be a direct neural target bound by human FOXP2 protein [47]. Mutations of FOXP2 and CNTNAP2 were linked to speech and language disorders and ASD [36, 37, 38, 48, 49, 50, 51]. Taken together, these data indicate that interactions among FOXP1, FOXP2, and CNTNAP2 genes may play an essential role underlying the pathogenesis of syndromic and non-syndromic ASD.

In a more recent study, forkhead box protein p1 was found to function as a transcriptional repressor of immune signaling in the mouse brain, and was involved in the pathophysiology of Huntington’s disease [52]. The study suggested that Foxp1-regulated pathways might be important mediators of neuronal-glial cell communication. Thus, the increased FOXP1 gene expression in the LCL of ASD patients as found in this study may offer a new insight that dysregulated immune signaling in the brain contributes to the pathogenesis of ASD."



Good to have you drop a line Benedetta. Yes, I went back and found my original research from many years ago about B vitamins and folate and our information agrees. I slipped into vitamin no mans land, but again remembered the interaction of b, folate and these matters. In our case sulpha drug gave a manifestation of phenylic sensitivity and PST/sulfate issues. Here is an email I received back from Dr. Shaw of Great Plains Lab about a question I had sent him back in 96.

Sulfur - Phenols and Phenolsulfotransferase

These drug interactions involving phenytoin,trimethoprim {Nick's note-Bactirm contains trimethoprim}, and sulfa drugs are extremely complex and unfortunately there is no easy answer for the reason for sensitivity to a particular drug. All of these drugs inhibit folic acid metabolism or transport, all of them may elicit allergic type reactions, all have complex routes of metabolic tranformation that may affect one another, and all of these may be metabolized by PST. Two of the drugs may have significant effects because of their antimicrobial action which changes the biochemistry of the GI tract by removing different groups of microorganisms.

William Shaw PhD

Dear Nick,

I have received the following answer to your question about sulfa drugs from Dr. Sinaiko, one of our

medical advisors:

Subject: Re:sulfonamides

Sulfonamides do, of course, contain sulfur in their chemical formulae.

Some brands will contain phenolic dyes.

I hope that has answered your question. If you need more information, feel free to ask.

Best wishes,

Hi all,

Many days ago, I have asked about cysteine, homocysteine (methionine) metabolism might be one of the possible link to seizures and neural disorders. I found one article about cysteine metabolism abnormality can link to phenolic metabolism abnormality.

Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways.

McFadden SA

Independent Research Advocates, Dallas, TX 75206, USA.

Toxicology 111: 43-65 (1996)


Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.

Yoshihisa Masuda

(Biotechnologist, Organic Chemist)

Also Ihave been looking for the element of the pathogen related to inflammation and the LPS source beyond that from a Leaky Gut, also the question arises as to why these cell walled pathogens gain a foot hold and are not destroyed by the immune system. I think Marshall's take and mycoplasma inhibit the immune system. anyway. Here is the report.

Bacterial cell wall mopping agents could treat chronic inflammatory diseases like type 2 diabetes

"Bacteria may be responsible for more than we suspect. Especially when it comes to inflammatory diseases such as type 2 diabetes.

Prof. Resia Pretorius from Stellenbosch University (SU) in South Africa and Prof. Douglas Kell from The University of Manchester have conducted a series of studies that are drastically changing the way scientists think about the effect bacteria have on a number of diseases including Alzheimer's disease, Parkinson's disease, Sepsis, Rheumatoid Arthritis, and most recently type 2 diabetes (T2D).

Previously, Pretorius and Kell have established that these chronic inflammatory diseases also have a microbial origin. "If the bacteria were active, or replicating, as in the case of infectious diseases, we would have known all about that," says Kell. "But the microbes are not replicating, they're mainly actually dormant."

Because their dormant nature meant that they did not manifest under standard microbial test conditions, bacteria were previously thought to be absent from human blood, consistent with the view that blood is 'sterile'. However, high levels of iron in blood (typical of inflammatory diseases) can effectively bring these bacteria back to life. Previous research suggested that under these conditions, the bacteria start replicating and secreting lipopolysaccharides (LPS), leading to increased inflammation.

The one thing these chronic diseases have in common is constantly elevated levels of inflammation. Pretorius and Kell had already established that anomalous amyloidogenic blood clotting, a cause of inflammation, is linked to and can be experimentally induced by bacterial cell wall constituents such as LPS and Lipoteichoic acid (LTA). These are cell wall components of Gram-negative and Gram-positive bacteria, respectively.

These coagulopathies (adverse blood clotting) are also typical of inflammatory diseases and the researchers have long shown that they lead to amyloid formation, where the blood clotting proteins (called fibrinogen) are structurally deformed from a-helixes to a flat b-sheet-like structures, potentially leading to cell death and neuro-degeneration.

As a result, the fibrin fibres of blood clots in diseased individuals are distinctly different from those of healthy individuals. This can be visualised microscopically and is discussed in various publications from the group. "In normal blood clots, these fibres would look like a bowl of spaghetti" explains Pretorius. "But in diseased individuals, their blood clots look matted with large fused and condensed fibres. They can also be observed with special stains that fluoresce in the presence of amyloid."

The researchers found that this changed clot structure is present in all inflammatory conditions studied, now including type 2 diabetes. But what is the link between this abnormal clot formation, bacteria, LPS and TLA? And are there any molecules that may "mop up" LPS or LTA and that might be circulating in the blood of people with inflammatory diseases?

In their 2017 study, recently published in Scientific Reports (a Nature publication), Pretorius and Kell, along with MSc student Ms Sthembile Mbotwe from the University of Pretoria, investigated the effect of LPS-binding protein (LBP), which is normally produced by all individuals. They added LBP to blood from T2D patients (and also to healthy blood after the addition of LPS). Previously they had showed that LPS causes abnormal clot formation when added to healthy blood, and that this could be reversed by LBP. In this publication they showed that LBP could also reverse the adverse clot structure in T2D blood. This process was confirmed by both scanning electron microscopy and super-resolution confocal microscopy. The conclusion is clear: bacterial LPS is a significant player in the development and maintenance of T2D and its disabling sequelae.

"In an inflamed situation, large amounts of LPS probably prevent LBP from doing its work properly," explains Pretorius.

So what does this mean in terms of treatment?

"We now have a considerable amount of evidence, much of it new, that in contrast to the current strategies for attacking T2D, the recognition that it involves dormant microbes, chronic inflammatory processes and coagulopathies, offer new opportunities for treatment," the researchers conclude. "


There was a study done that included around 5500 people.
Vitamin Bs did lower the occurrence of strokes.
However; if a stroke did occur it did not make any difference in how severe those strokes could be even if you were taking the B vitamins.

I thought they meant a regular B complex. Oh how I wish it was that simple

What they were taking as folic acid, B 6 and B12.

I am trying to reduce the pills my family is taking.
Also the amount of folic, B6 and B12 were rather high. I need to look at that study again if I can find it.

Oh, and a VA doctor told Dad back 15 years ago that he had Parkinsons.
We finally got around to going to see a neurologist today. Apparently Dad had a stroke 15 years ago, all following soon after a flu shot.

Apparently there are things that are Parkinson like, injuries to the brain. His was in the basal ganglia, and damaged some of the dopamine producing cells. That is how I understood it.


Thanks Visitor. B 6


Vitamin B6 prevents IL-1β production by inhibiting NLRP3 inflammasome activation


"Vitamin B6 includes six water-soluble vitamers: pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), and their phosphorylated forms. Pyridoxal 5'-phosphate (PLP) is an important cofactor for many metabolic enzymes. Several lines of evidence demonstrate that blood levels of PLP are significantly lower in patients with inflammation than in control subjects, and that vitamin B6 has anti-inflammatory effects, with therapeutic potential for a variety of inflammatory diseases. Although one of our group (NK) previously demonstrated that PL inhibits the NF-κB pathway, the molecular mechanism by which vitamin B6 suppresses inflammation is not well understood. Here, we showed that both PL and PLP suppressed the expression of cytokine genes in macrophages by inhibiting TLR-mediated TAK1 phosphorylation and the subsequent NF-κB and JNK activation. Furthermore, PL and PLP abolished NLRP3-dependent caspase-1 processing and the subsequent secretion of mature IL-1β and IL-18 in LPS-primed macrophages. In contrast, PM and PN had little effect on IL-1β production. PLP, but not PL, markedly reduced the production of mitochondrial reactive oxygen species (ROS) in peritoneal macrophages. Importantly, PL and PLP reduced the IL-1β production induced by LPS and ATP, or by LPS alone, in mice. Moreover, PL and PLP protected mice from lethal endotoxic shock. Collectively, these findings reveal novel anti-inflammatory activities for vitamin B6, and suggest its potential for preventing inflammatory diseases driven by the NLRP3 inflammasome."


B6 alone taxes PST though.


A similar event, some triggered by MMR, may effect the gut and induce cytokines production and bbb permeability with a flow of T Cells effecting the vessels and areas mentioned in this report. I don't know if Tcells in peripheral circulation would lower due to this occurring, but it would be interesting to know. This does not speak directly to Autism and gastro interaction and details mortality due to gastro dysfunction in mice, it sounds like it shares some of the pathology for many.

Very worthwhile.

Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit

Moreover, neutralization of the Th1 cytokine, interferon-gamma (IFN-γ), or that of the Th17 cytokine, IL-17A, also inhibited the brain micro-inflammation at the specific vessels (Figure 4E). Importantly, the accumulation of IL-17A- or IFN-γ-deficient pathogenic CD4+ T cells was significantly reduced at the specific blood vessels under stress conditions and resulted in less mortality (Figure 4—figure supplement 3). These data suggested that both IFN-γ and IL-17A from pathogenic CD4+ T cells are necessary for the accumulation at specific vessels and the severe phenotypes. Consistent with these results, prominent inhibitory effects on the disease development were observed with combined neutralization of IL-17A and IFN-γ(Figure 4F). These results suggested that stress-mediated CCL5 expression at the specific vessels induces the accumulation of pathogenic CD4+ T cells, particularly Th17 and Th1 cells and MHC class IIhiCD11b+ cells to establish brain micro-inflammation, which is critical for the development of fatal gastrointestinal failure. We call this phenomenon the stress-gateway reflex.

Brain micro-inflammation at specific vessels is sufficient to induce fatal gastrointestinal failure under stress condition

"We next investigated whether brain micro-inflammation at the specific vessels is sufficient to develop intestinal failure in mice under stress. To answer this question, we directly microinjected pathogenic CD4+ T cells plus MOG-pulsed DC or inflammatory cytokines, such as IFN-γ plus IL-17A or IL-6 plus IL-17A, either of which is known to be expressed by pathogenic CD4+ T cells and enhance chemokine expression at specific vessels in gateway reflexes previously identified (Arima et al., 2012; Sabharwal et al., 2014), at specific vessels of the boundary region of the third ventricle region, thalamus, and dentate gyrus under stress condition. We found that brain micro-inflammation induced by these treatments developed severe gastrointestinal failure and affected mortality (Figure 4G). Furthermore, we investigated the mortality of mice with microinjections of cytokines at the specific vessels under stress condition in the presence or absence of anti-CCL5 antibody treatment and found anti-CCL5 antibody treatment had no significant effect (Figure 4—figure supplement 4). This result suggested that CCL5 mainly contributes to the accumulation of immune cells including pathogenic CD4+ T cells at the specific vessels, while the effect of cytokine injection is CCL5-independent. These results suggest that brain micro-inflammation at the specific vessels, which is triggered by CCL5-mediated pathogenic CD4+ T cell accumulation, induces regional cytokine increment followed by severe gastrointestinal failure under stress condition."...

"Flow cytometry analysis confirmed an abundance of immune cell accumulation including pathogenic CD4+ T cells and MHC class IIhiCD11b+ cells in the hippocampus and interbrain area, where the specific vessels were localized (Figure 3C). Td-tomato labeling of microglia cells, which we used previously (Arima et al., 2015), revealed that MHC class IIhiCD11b+ cells originated from the peripheral organs rather than resident microglia cells (Figure 3D), suggesting that the MHC class IIhiCD11b+ cells that accumulated at the specific vessels were activated monocytes from the peripheral organs. Moreover, we found that various immune cells, including CD8+ T cells, B cells, NK cells, and neutrophils, had also accumulated at the specific vessels (Figure 3—figure supplement 2). Thus, the stress condition induced brain micro-inflammation at specific vessels of the boundary area of the third ventricle region, thalamus, and dentate gyrus in the transfer EAE model."



HMGB1, Autism, Kawasaki's

High-mobility group box 1 (HMGB1) in childhood: From bench to bedside

Autistic disorders
"Autism is a neurodevelopmental disability characterized by
impairments in verbal communications, reciprocal social in-
teractions, and restricted repetitive stereotyped behaviors [84].
Dysregulated immune function is a recurrent finding, includ-
ing evidence of brain reactive antibodies, altered cytokine levels
in the brain, and altered function of innate immune cells [96].
HMGB1 receptors are involved in the pathophysiological
mechanisms of autism. Enstrom et al. described abnormal sen-
sitivity of peripheral blood monocytes, isolated from children
with and without autism, to TLR ligands, suggesting a dysfunc-
tion in monocyte pathogen recognition and/or TLR signaling
pathways [43]. Junaid et al. showed high incidence of A-allele
homozygosis in the GLO1 gene, with reduction in Glo1 activity
[61]. This condition determines an accumulation in the brain of
methylglyoxal, leading to the formation of advanced glycosyl-
ated end products (AGE), which ultimately induces the RAGE-
mediated downstream signaling cascade [13]. Autistic children
are also characterized by abnormal serum levels of HMGB1
when compared with healthy controls [42].
High serum levels of HMGB1 may be a biomarker of the
impaired reciprocal social interactions in this
neurodevelopmental disorder."

Kawasaki disease
"Kawasaki disease (KD) is an acute, self-limited vasculitis,
with potential cardiovascular complications, developing in ∼
15 to 25 % of untreated children [79].
Hoshina et al. measured HMGB1 levels in 27 children
affected by KD, demonstrating higher HMGB1 values than
healthy controls. Furthermore, the highest values were detected
in early acute phase with a gradually decrement after deferves-
cence [55]. In addition, analyzing KD patients after intravenous
immunoglobulin treatment, Eguchi et al. demonstrated that poor-responder group was characterized by high HMGB1, representing a potential marker of therapy resistance [40]."

The abve found in this pdf.



There is so much I could post but some would be more specific to a sub type or co-morbid aspects bearing on the condition. Stepping back I feel I'm mostly done with my puzzle in the primary ways and a great deal of the detail. This piece is behind a pay wall, but is looking into the metabolic involvement in inflammation.

Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses.

"Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. The signals activating other inflammasomes, NLRP3, NLRP6, and pyrin, are less well understood. Recent studies implicated several low-molecular-weight compounds traditionally linked to metabolism, not immunity, in modulation of inflammasome signaling. Furthermore, genetic, pharmacological, or pathogen-mediated interference with energy metabolism also affects inflammasome activation. Here we review the findings on how microbial- and host-derived metabolites regulate activation of the NLRP3 and NLRP6 inflammasomes. We discuss the different models of how glycolysis and mitochondrial metabolism control the NLRP3 inflammasome. Finally, we summarize the findings on metabolic control of pyrin and point to open questions to be addressed to broaden our understanding of metabolism-inflammasome interactions."



Found this quite interesting as the cytokines mentioned are ones that keep surfacing with Autism and other brain related conditions involving the innate immune system. The second report ties THril gene mentioned related to Autism in the first report to Kawasaki disease as well.

Immunological cytokine profiling identifies TNF-α as a key molecule dysregulated in autistic children.


"Recent studies have suggested that the etiology of Autism Spectrum Disorder (ASD) may be caused by immunological factors, particularly abnormalities in the innate immune system. However, it is still unclear which specific cytokines may be of most importance. The current study therefore investigated which cytokines showed altered concentrations in blood in ASD compared with healthy control children and which were also correlated with symptom severity. Our study sample included 32 children diagnosed with ASD and 28 age and sex-matched typically developing children. Autism symptoms were measured using the Autistic Behavior Checklist (ABC) and blood samples were taken from all subjects. We used Milliplex cytokine kits to determine serum concentrations of 11 Th1, Th2 and Th17 related cytokines. Additionally, expression of THRIL (TNFα and hnRNPL related immunoregulatory LincRNA), a long non-coding RNA involved in the regulation of tumor necrosis factor- α (TNF-α), was determined using real-time PCR. Of the 11 cytokines measured only concentrations of TNF-α (p=0.002), IL-1β (p=0.02) and IL-17a (p=0.049) were significantly increased in ASD children compared to typically developing controls, but only TNF-α concentrations were positively correlated with severity of ASD symptoms on all 5 different ABC sub-scales and were predictive of an ASD phenotype (area under the curve = 0.74). Furthermore, THRIL RNA expression was significantly decreased in ASD children. Our results provide further support for altered innate immunity being an important autism pathogenic factor, with autistic children showing increased blood TNF-α concentrations associated with symptom severity, and decreased expression of the THRIL gene involved in regulating TNF-α."


The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL.


"Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNFα expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992-hnRNPL complex that regulated transcription of the TNFα gene by binding to its promoter. Transcriptome analysis revealed that linc1992 was required for expression of many immune-response genes, including other cytokines and transcriptional and posttranscriptional regulators of TNFα expression, and that knockdown of linc1992 caused dysregulation of these genes during innate activation of THP1 macrophages. Therefore, we named linc1992 THRIL (TNFα and hnRNPL related immunoregulatory LincRNA). Finally, THRIL expression was correlated with the severity of symptoms in patients with Kawasaki disease, an acute inflammatory disease of childhood. Collectively, our data provide evidence that lincRNAs and their binding proteins can regulate TNFα expression and may play important roles in the innate immune response and inflammatory diseases in humans."



There is a lot to be gleaned from these two reports regarding a lot of Autism as there appears to be core relationships between the three conditions discussed and much Autism All throughout this thread I have alluded to studies about these three as they overlap with Autism biology dysfunction . Maybe I will post some of the things I see in the future. If you keep in my gene expression and the aspects of the cell types in the first report, esp. microglia, you might find it of interest. You can even understand the benefits of Metformin.

Cell specificity dictates similarities in gene expression in multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease


"Drug repurposing is an efficient approach in new treatment development since it leverages previous work from one disease to another. While multiple sclerosis (MS), Parkinson’s disease (PD), and Alzheimer’s disease (AD) are all neurodegenerative diseases of the central nervous system (CNS) and differ in many clinical and pathological aspects, it is possible that they may share some mechanistic features. We hypothesized that focusing on gene expression in a CNS cell type specific manner might uncover similarities between diseases that could be missed using whole tissue gene expression analyses. We found similarities and differences in gene expression in these three distinct diseases, depending upon cell type. Microglia genes were increased in all three diseases, and gene expression levels were correlated strongly among these three neurodegenerative diseases. In astrocytes and endothelia, upregulation and correlations were observed only between MS and PD, but not AD. Neuronal genes were down-regulated in all three diseases, but correlations of changes of individual genes between diseases were not strong. Oligodendrocyte showed gene expression changes that were not shared among the three diseases. Together these data suggest that treatments targeting microglia are most amenable to drug repurposing in MS, PD, and AD, while treatments targeting other CNS cells must be tailored to each disease."


Gene Expression from study

An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia


"The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a central role in the transcriptional response to oxygen flux. To gain insight into the molecular pathways regulated by HIF-1, it is essential to identify the downstream-target genes. We report here a strategy to identify HIF-1-target genes based on an integrative genomic approach combining computational strategies and experimental validation. To identify HIF-1-target genes microarrays data sets were used to rank genes based on their differential response to hypoxia. The proximal promoters of these genes were then analyzed for the presence of conserved HIF-1-binding sites. Genes were scored and ranked based on their response to hypoxia and their HIF-binding site score. Using this strategy we recovered 41% of the previously confirmed HIF-1-target genes that responded to hypoxia in the microarrays and provide a catalogue of predicted HIF-1 targets. We present experimental validation for ANKRD37 as a novel HIF-1-target gene. Together these analyses demonstrate the potential to recover novel HIF-1-target genes and the discovery of mammalian-regulatory elements operative in the context of microarray data sets."



Supplementary Table s6 Files within file download
Particularly File013 and File014


I missed this excellent article and Visitor addendums when it was first published in 2015 and the only way I knew about it was the "Visitor" link in the sidebar comments.


Worth a read. Aluminum mainly. PDF



Saw this when it cam out, but it lends credence to barrier function issues in Autism.

Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.



"Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD.


Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated.


Claudin (CLDN)-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3, tricellulin, and MMP-9 were higher in the ASD cortex. IL-8, tPA, and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components (CLDN-1, OCLN, TRIC), whereas 66% had increased pore-forming CLDNs (CLDN-2, -10, -15) compared to controls.


In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies."


High Levels of Pro-Inflammatory Immune Cells in Intestines May Promote MS Activity, Study Reports

"People with multiple sclerosis have high levels of pro-inflammatory TH17 immune cells in their intestines that correlate with change in the micro-organism mix in their gut and the levels of their disease activity, a study reports.

Researchers said the findings suggest that diet, probiotics and therapies that regulate TH17 cells could help treat MS. Probiotics are supplements containing beneficial bacteria.

The study, “High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis,” was published in the journal Science.

Research has shown that TH17 cells, also known as T helper 17 cells, play a role in the development of MS. In fact, they were the first harmful immune T-cells to infiltrate the central nervous system, according to studies in animals

Where TH17 cells become activated has been unclear, however. Studies in mice suggested it was mainly in the small intestine. Research has also indicated that their activation increases the potential for a person to develop an autoimmune brain disease like multiple sclerosis.

An autoimmune disease occurs when the immune system, which defends the body against disease, decides that a person’s healthy cells are foreign, and attacks those cells.

Researchers decided to see if the findings in mouse models of MS applied to people with the disease.

They discovered a link between higher levels of TH17 cells in MS patients’ intestines and autoimmune brain problems. They also found a correlation between higher levels of TH17 cells and changes in patients’ gut microbiome.

The team then identified which bacteria were changing in the gut.

Patients with increased levels of TH17 cells and higher disease activity had a higher ratio of Firmicutes to Bacteroidetes bacteria and more Streptococcus strains in their gut, particularly Streptococcus mitis and Streptococcus oralis. Previous studies have shown that these species promote TH17 cell differentiation in humans.

Cell differentiation involves a cell transforming from one cell type to another — usually a more specialized type. This dramatically changes a cell’s size, shape, metabolic — or fuel-burning — activity, and responsiveness to signals. Some studies have suggested a link between T-cell differentiation and brain autoimmune diseases.

“On the basis of our findings, we speculate that, under certain conditions, or because of still unknown virulence factors, these Streptococcus strains can colonize the small intestine and favor TH17 cell differentiation in the human gut mucosa [linings],” researchers wrote.

In addition to more Streptococcus bacteria, the team detected lower levels of Prevotella bacteria in MS patients with disease activity than in healthy controls or patients with no disease activity. This decrease may also promote TH17 cell differentiation because “Prevotella is capable of producing the anti-inflammatory metabolite propionate that limits intestinal TH17 cell expansion in mice,” the researchers wrote.

Overall, the team concluded that “our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive TH17 cell expansion in the human intestine.”

The findings suggest that regulating TH17 cell expansion, along with changes in diet aimed at regulating intestinal linings, could be ways to help treat MS."



This has some very good thoughts.

More Pieces To The Puzzle… Iron, Mercury, Sulfur, Fetal Hemoglobin, Heme Deficiency, Aluminum, Insulin, Gestational Diabetes, and B6



Some good pieces that show the connection of certain factors like sulfate and leaky gut issues. worthwhile though many probably know these basics. Mutations figure in too.
Nat2 and Sult function invoked here too.

Oxalates and MTHFR: Understanding the Gut-Kidney Axis




This anecdote is appropriate here I think:
From a board posting of a mother about her daughter.

"My daughter's results showed homozygous mutations in:




Which I'm guessing means to supplement with Vitamins B12 and D??? I don't really know what else to do. What kind of doctor could help look at this stuff or is it all up to us.... (as usual).....

"And the heterozygous mutations were in:

COMT v158M




MTR A2756G



CYP1A2 164A>C

Cyp2C9*3 A1075C

CYP2D6 S486T

CYP2D6 2850C>T


NAT2 I114T

NAT2 K268R

Any opinions greatly appreciated...."



Antigliadin Antibodies (AGA IgG) Are Related to Neurochemistry in Schizophrenia



The obligatory countenancing of scientists of the past having previously made assertions about certain biological connections to a certain medical issue is at times reasonable, but this first article uses this tact in saying the gut has long been associated by scientist with autism. Maybe so, but I shave followed this long enough to know that those that did were never taken seriously by the "establishment" of medicine and until fairly recently it was not taken seriously enough to investigate in mainstream medical institutions. Advocates of diet, probiotics, and other gut related supplements and nutrients were fighting an uphill battle. At least this may mean a corner is being turned, still why not say "some have proposed this and were usually dismissed."

Treating autism by targeting the gut

"Many of the papers reviewed support the idea of a gut-brain axis -- a way in which factors in the gut can affect processes in the brain. So these gastro-intestinal problems may have a more sinister side. The overgrowth of bad bacteria in the gut inevitably leads to an overproduction of by-products -- including toxins. These can make the gut lining more permeable. Then toxins, by-products and even undigested food can get into the bloodstream and travel to the brain....

However, the researchers found a significant body of evidence that reverting the gut microbiota to a healthy state can reduce ASD symptoms.

"Efforts to restore the gut microbiota to that of a healthy person has been shown to be really effective" continues Dr Li. "Our review looked at taking probiotics, prebiotics, changing the diet -- for example, to gluten- and casein-free diets, and faecal matter transplants. All had a positive impact on symptoms ."


and this with aspects of inflammation like much autism.

Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder


Mouse Study: Psychiatric Symptoms in Lupus Patients Tied to Inflammation



Trust any reading these will know their relevance. I just came across these studies, but they fit with all of things in this thread and agree with things I dealt with long ago. Sanity is overrated.

Low-grade endotoxemia in patients with severe autism {scroll down a bit for study}


Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder


Plasma Cytokine Profiles in Subjects with High-Functioning Autism Spectrum Disorders


Serum levels of vascular endothelial growth factor and its receptors in patients with severe autism


Alterations of circulating endogenous secretory RAGE and S100A9 levels indicating dysfunction of the AGE-RAGE axis in autism



Not totally futile. I am not myself on occasion.



I tried my best. It is futile.





Tuesday, May 23rd 2017 2PM 80°F 5PM 72°F 5-Day Forecast




Tuesday, May 23rd 2017 2PM 80°F 5PM 72°F 5-Day Forecast

Autism is linked to intelligence: People with 'smart genes' are more likely to have the disorder

Autism is linked to intelligence: People with 'smart genes' are more likely to have the disorder

I am heuristic, but this must be true.


Can anyone help me? See projection.

Autism is linked to intelligence: People with 'smart genes' are more likely to have the disorder


The Morning After by Maureen McGovern



Visitor: bringing new science into the public light always makes a difference, whether or not you ever personally witness the difference that it makes. Let me tell you how it makes a difference to me. My child had tics as an infant. It's THE main reason I slowed down and broke up school vaccinations for that child. Luckily, that symptom disappeared over time. Your information makes me very glad I was cautious at the time. I wish I had been even more cautious. Also, there is a friend I know well whose child has had tics since early childhood, still has them, but recently asked me about the meningitis vaccine, a shot I know less about but didn't it have a very small test subject group in southern south america somewhere, about as far away from standard US environmentally influenced kids as one could get. You know I will forward your information to my friend. It's about time other medical / neurological issues were examined in light of vaccine administration - and regularly discussed. It's especially important because it's easy to pawn off vaccine problems when the subject is a baby who can't talk - like those in the age range the doctor at UC David MIND limits himself to. The age range is much expanded in your reference - to children that may have been fine and dandy, until additional vaccinations. And they can TALK about it. You should repost this under Anne Dachel's post today.


Time to feed the beast.

II have found a lot since I last posted here, but doubt it makes any difference in posting all I discover. But, here is a new release on Pub Med. It talks about how the MMR has been clearly shown to have nothing to do with Autism and proceeds to test an association between vaccinations and other conditions excluding Autism. They find an association, or as they say "temporally related". They then say that because of the value of vaccines keep up the shots. Yet, they add "These findings warrant further investigation" but basically prove nothing. In the end signs point to yes, but yes is never an option.
Someone will surely pummel them over doing this study even though there is direct indictment of vaccines and any thinking reader would have to ask "is there a connection or not?".

Temporal Association of Certain Neuropsychiatric Disorders Following Vaccination of Children and Adolescents: A Pilot Case-Control Study.



"Although the association of the measles, mumps, and rubella vaccine with autism spectrum disorder has been convincingly disproven, the onset of certain brain-related autoimmune and inflammatory disorders has been found to be temporally associated with the antecedent administration of various vaccines. This study examines whether antecedent vaccinations are associated with increased incidence of obsessive-compulsive disorder (OCD), anorexia nervosa (AN), anxiety disorder, chronic tic disorder, attention deficit hyperactivity disorder, major depressive disorder, and bipolar disorder in a national sample of privately insured children.


Using claims data, we compared the prior year's occurrence of vaccinations in children and adolescents aged 6-15 years with the above neuropsychiatric disorders that were newly diagnosed between January 2002 and December 2007, as well as two control conditions, broken bones and open wounds. Subjects were matched with controls according to age, gender, geographical area, and seasonality. Conditional logistic regression models were used to determine the association of prior vaccinations with each condition.


Subjects with newly diagnosed AN were more likely than controls to have had any vaccination in the previous 3 months [hazard ratio (HR) 1.80, 95% confidence interval 1.21-2.68]. Influenza vaccinations during the prior 3, 6, and 12 months were also associated with incident diagnoses of AN, OCD, and an anxiety disorder. Several other associations were also significant with HRs greater than 1.40 (hepatitis A with OCD and AN; hepatitis B with AN; and meningitis with AN and chronic tic disorder).


This pilot epidemiologic analysis implies that the onset of some neuropsychiatric disorders may be temporally related to prior vaccinations in a subset of individuals. These findings warrant further investigation, but do not prove a causal role of antecedent infections or vaccinations in the pathoetiology of these conditions. Given the modest magnitude of these findings in contrast to the clear public health benefits of the timely administration of vaccines in preventing mortality and morbidity in childhood infectious diseases, we encourage families to maintain vaccination schedules according to CDC guidelines."


anorexia nervosa; anxiety disorder; influenza; meningococcus; obsessive–compulsive disorder; tic disorder; vaccination



I messed the order of the last post up. Here is how it should be ordered.

This is another that is preliminary, but seems accurate. They think the treatment targets the NLRP3 pathway which is one of the areas I have found relevant, at least in our case. NLRP3 or NALP3 laced through this thread.

Pill for Menstrual Pain Restores Memory in Mice with Alzheimer's

"A surprising discovery has been made in the treatment of Alzheimer's disease. An anti-inflammatory drug used to treat menstrual pain completely reversed memory symptoms in mice with Alzheimer's.

The drug, called mefenamic acid, is a so-called non-steroidal anti-inflammatory drug, or NSAID, used to relieve menstrual cramps.

In experiments with mice specially bred to have Alzheimer's symptoms, the rodents predictably developed memory problems over time.

Ten of the Alzheimer's mice were treated for one month with mefenamic acid that was contained in tiny pumps implanted under their skin. Ten other mice with memory difficulties were injected with pumps of a placebo, or inactive substance.

The rodents were placed in maze to train them to get around the obstacles.

In a Skype interview, Mike Daniels, who participated in the research at the University of Manchester in Britain, said "We tried to train the mice once they had Alzheimer's disease. The Alzheimer's mice are untrainable. They cannot learn that maze."

"But the results in the treated mice were stunning."

"What was just amazing is that this drug seemed to render the mice completely normal,” Daniels said. “It's something we haven't really seen before, but there needs to be a lot more work done to really confirm whether this is real.”

Targeting inflammation

"The findings were published in the journal Nature Communications. The research was led by David Brough of the University of Manchester."

Daniels said brain-imaging shows a lot of harmful inflammation in the brains of Alzheimer's patients.

"Researchers believe mefenamic acid targets an inflammatory pathway called NLRP3, reducing inflammation."

"Scientist found that no other NSAIDS — including ibuprofen, which is commonly taken for pain — reduced the brain inflammation."

"Whether it works in patients at all stages of Alzheimer's — from people with mild cognitive impairment to those who are severely affected — is difficult to say, according to co-author Jack Rivers-Auty."

"Maybe, if this was translated into the clinic, we would definitely want to put it into people at the early stages of the disease to try to slow the progress or stop the progress of the disease," said Rivers-Auty, "rather than taking the ambitious aim of taking someone who fully has Alzheimer's disease, has all the symptoms — incredible memory loss, incredible cognitive impairment — and trying to reverse those symptoms. That might be very difficult."


Multiple inflammasome complexes are activated in autistic spectrum disorders.


"Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation.


The activity of the inflammasomes, the concentration of the inflammasomes-derived proinflammatory cytokines interleukin (IL)-1β and IL-18, and serum parameters of GI damage were analyzed in 25 ASD children, 23 healthy siblings (HS) and 30 unrelated age-matched healthy controls (HC).


A significant upregulation of the AIM2 and the NLRP3 inflammasomes and an increased production of IL-1β and IL-18 that was associated with a consistent reduction of IL-33, an anti inflammation cytokine were observed in ASD alone. Notably, in a possible immune-mediated attempt to dampen inflammation, IL-37, a suppressor of innate inflammatory responses, was significantly augmented in these same children. Finally, intestinal fatty acid binding protein (IFABP), an index of altered GI permeability, was significantly increased in serum of ASD and HS.


These results show that the inflammasomes are activated in ASD and shed light on the molecular mechanisms responsible for ASD-associated neuroinflammation. The observation that GI alterations could be present as well in ASD offers a possible link between such alterations and neuroinflammation. Therapeutic strategies targeting inflammasome activation could be useful in ASD."



This is another that is preliminary, but seems accurate. They think the treatment targets the NLRP3 pathway which is one of the areas I have found relevant, at least in our case. NLRP3 or NALP3 laced through this thread.

Pill for Menstrual Pain Restores Memory in Mice with Alzheimer's

"A surprising discovery has been made in the treatment of Alzheimer's disease. An anti-inflammatory drug used to treat menstrual pain completely reversed memory symptoms in mice with Alzheimer's.

The drug, called mefenamic acid, is a so-called non-steroidal anti-inflammatory drug, or NSAID, used to relieve menstrual cramps.

In experiments with mice specially bred to have Alzheimer's symptoms, the rodents predictably developed memory problems over time.

Ten of the Alzheimer's mice were treated for one month with mefenamic acid that was contained in tiny pumps implanted under their skin. Ten other mice with memory difficulties were injected with pumps of a placebo, or inactive substance.

The rodents were placed in maze to train them to get around the obstacles.

In a Skype interview, Mike Daniels, who participated in the research at the University of Manchester in Britain, said "We tried to train the mice once they had Alzheimer's disease. The Alzheimer's mice are untrainable. They cannot learn that maze."

"But the results in the treated mice were stunning."

"What was just amazing is that this drug seemed to render the mice completely normal,” Daniels said. “It's something we haven't really seen before, but there needs to be a lot more work done to really confirm whether this is real.”


Multiple inflammasome complexes are activated in autistic spectrum disorders.


"Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation.


The activity of the inflammasomes, the concentration of the inflammasomes-derived proinflammatory cytokines interleukin (IL)-1β and IL-18, and serum parameters of GI damage were analyzed in 25 ASD children, 23 healthy siblings (HS) and 30 unrelated age-matched healthy controls (HC).


A significant upregulation of the AIM2 and the NLRP3 inflammasomes and an increased production of IL-1β and IL-18 that was associated with a consistent reduction of IL-33, an anti inflammation cytokine were observed in ASD alone. Notably, in a possible immune-mediated attempt to dampen inflammation, IL-37, a suppressor of innate inflammatory responses, was significantly augmented in these same children. Finally, intestinal fatty acid binding protein (IFABP), an index of altered GI permeability, was significantly increased in serum of ASD and HS.


These results show that the inflammasomes are activated in ASD and shed light on the molecular mechanisms responsible for ASD-associated neuroinflammation. The observation that GI alterations could be present as well in ASD offers a possible link between such alterations and neuroinflammation. Therapeutic strategies targeting inflammasome activation could be useful in ASD."

Targeting inflammation

"The findings were published in the journal Nature Communications. The research was led by David Brough of the University of Manchester."

Daniels said brain-imaging shows a lot of harmful inflammation in the brains of Alzheimer's patients.

"Researchers believe mefenamic acid targets an inflammatory pathway called NLRP3, reducing inflammation."

"Scientist found that no other NSAIDS — including ibuprofen, which is commonly taken for pain — reduced the brain inflammation."

"Whether it works in patients at all stages of Alzheimer's — from people with mild cognitive impairment to those who are severely affected — is difficult to say, according to co-author Jack Rivers-Auty."

"Maybe, if this was translated into the clinic, we would definitely want to put it into people at the early stages of the disease to try to slow the progress or stop the progress of the disease," said Rivers-Auty, "rather than taking the ambitious aim of taking someone who fully has Alzheimer's disease, has all the symptoms — incredible memory loss, incredible cognitive impairment — and trying to reverse those symptoms. That might be very difficult."



Some would say this requires more confirmation, other studies would align with this report. My own experience says it is legitimate.

Wheat can cause immune response in people without Celiac disease, study says

'People with a wheat sensitivity, but not celiac's disease or a wheat allergy, are not imagining symptoms they feel after eating wheat, according to a new study.

Researchers at Columbia University Medical Center report people without celiac's disease can experience a body-wide immune response to wheat thought to be related to intestinal cell damage and a weakening of the intestinal barrier, which may suggest a method of identifying and treating the condition.

Celiac disease is a genetic autoimmune disorder causing an immune response to gluten -- found in wheat, barley and rye -- attacking the lining of the small intestine, causing abdominal pain, diarrhea and bloating.

With growing awareness of celiac disease in recent years, the popularity of a gluten-free diet has also grown. Researchers in other studies have suggested a gluten-free diet is unhealthy in the absence of a condition like celiac.

The new study suggests non-celiac gluten or wheat sensitivity, or NCWS, can be identified in patients based on system-wide inflammation caused by the grains.

"These results shift the paradigm in our recognition and understanding of non-celiac wheat sensitivity and will likely have important implications for diagnosis and treatment," Dr. Umberto Volta, a professor of internal medicine at the University of Bologna, said in a press release. "Considering the large number of people affected by the condition and its significant negative health impact on patients, this is an important area of research that deserves much more attention and funding."

For the study, published in the journal BMJ Gut, researchers examined 80 people with NCWS, 40 with celiac disease and 40 who were healthy.

While both celiac and NCWS patients showed damage to their small intestines similar to celiac disease, NCWS patients showed signs of innate systemic immune activation. The researchers say this indicates a completely different response to wheat or gluten they link to intestinal cell damage and weakening of the intestinal barrier.

Patients in the study with NCWS who consumed a gluten-free diet for six months saw their immune systems calm down and reported symptoms subsided the longer they stayed on the diet.

"Our study shows that the symptoms reported by individuals with this condition are not imagined, as some people have suggested," said Dr. Peter Green, director of the Celiac Disease Center at Columbia University. "It demonstrates that there is a biological basis for these symptoms in a significant number of these patients."


If I could bold some of the words I would have bolded these:
"system-wide inflammation caused by the grains"
"NCWS patients showed signs of innate systemic immune activation."
"Patients in the study with NCWS who consumed a gluten-free diet for six months saw their immune systems calm down and reported symptoms subsided the longer they stayed on the diet."


Does the Immune System Have a Role in Battling Autism?



Hi Grace, you are welcome. How vaccines tie to interferon-γ, also labeled Interferon Gamma, is of interest. A number of posts in this thread address aspects of interferon-γ as it may pertain to Autism. I think the article goes a bit far suggesting we may simply be a platform for immune/pathogen evolution, but there does appear to be a strong symbiosis and a early and/or strong continuous dysfunction in this and other immune related function with pathogens could alter neurological function and development.

Another report just released addressing the same information adds more possible light.

Does the Immune System Have a Role in Battling Autism?

"Replenishing the spinal fluid of the mice with interferon gamma is enough to restore social behavior in the mice. Diazepam, a sedative that boosts the activity of inhibitory neurons, has the same effect."...

"If the immune system evolved alongside social behavior, this might explain the results of other autism studies. A study published earlier this year, for example, suggests that some pregnant women who go on to have children with autism and intellectual disability have elevated blood levels of interferon gamma."

"This result may seem at odds with the finding that interferon gamma is needed for social behavior, but too much of the molecule might shut off its activity."

"The role of immune molecules in the brain is likely to be a delicate balance, with specific levels needed at specific times, says Pardo-Villamizar. “The immune system during brain development works like an orchestra,” he says.

"The findings may explain the observation that some children with autism seem to become more sociable when they have a fever, Kipnis says. Elevated levels of molecules such as interferon gamma accompany fevers."

"Kipnis says understanding the immune link to social behavior might help scientists find drugs that treat autism. Clinicians might be able to administer the treatment in the cerebrospinal fluid, he says, rather than via the brain."


A few years back in this thread I had posted this:

"Autism: An Overview"

Written and Maintained by Lewis Mehl-Madrona, M.D., Ph.D.

"Gamma Interferon Theory

Dr. Vijendra Singh has found elevated levels of interleukin-12 and gamma interferon in autistic patients. Opioids can increase levels of gamma interferon."

The rest of that post also spoke of how NK cells and T-Lymphocytes. The quote acutally is:
"Sulfation problems have been described by Rosemary Waring at the University of Birmingham in autism which could lead to an inability to handle virus infections, with a disruption of cell-mediated immunity® as well as an impairment of natural killer cell function.® Unlike the situation with type I interferons, which are released by infected cells, interferon gamma (a type II interferon) is released by T lymphocytes and natural killer cells, but that happens not when they themselves have been activated, but rather, when they are alerted to the presence of infection by other immune cells or by a superantigen or a chemical mitogen."

So, while it appears to be that interferon Gamma is a player in some amount of autism weather it is too much or too little or even a vacillating amount that is the problem is still something I have not found an answer.

The link to the latter in I quoted can be found under the heading:
Gamma Interferon Theory at the link below
http://www.healing-arts.org/children/autism-overview.htm#Gamma Interferon

Grace Green

Thank you, Visitor, for posting this find. This sounds to me very much like "Vaccines cause Autism (M.E./Alzheimers etc.). I look forward to hearing how this progresses.


This report postulates the general ideas of effects of the immune system/pathogen interaction and brain function and social behavior. It alludes to involving Autism though our case was extreme with a reactive social condition , one without autonomy.

Shocking New Role Found for the Immune System: Controlling Social Interactions

"In a startling discovery that raises fundamental questions about human behavior, researchers at the University of Virginia School of Medicine have determined that the immune system directly affects – and even controls – creatures’ social behavior, such as their desire to interact with others.

So could immune system problems contribute to an inability to have normal social interactions? The answer appears to be yes, and that finding could have significant implications for neurological diseases such as autism-spectrum disorders and schizophrenia.

“The brain and the adaptive immune system were thought to be isolated from each other, and any immune activity in the brain was perceived as sign of a pathology. And now, not only are we showing that they are closely interacting, but some of our behavior traits might have evolved because of our immune response to pathogens,” explained Jonathan Kipnis, Ph.D., chairman of UVA’s Department of Neuroscience. “It’s crazy, but maybe we are just multicellular battlefields for two ancient forces: pathogens and the immune system. Part of our personality may actually be dictated by the immune system.”...

"It was only last year that Kipnis, the director of UVA’s Center for Brain Immunology and Glia, and his team discovered that meningeal vessels directly link the brain with the lymphatic system. That overturned decades of textbook teaching that the brain was “immune privileged,” lacking a direct connection to the immune system. The discovery opened the door for entirely new ways of thinking about how the brain and the immune system interact."

"The follow-up finding is equally illuminating, shedding light on both the workings of the brain and on evolution itself. The relationship between people and pathogens, the researchers suggest, could have directly affected the development of our social behavior, allowing us to engage in the social interactions necessary for the survival of the species while developing ways for our immune systems to protect us from the diseases that accompany those interactions. Social behavior is, of course, in the interest of pathogens, as it allows them to spread."

"The UVA researchers have shown that a specific immune molecule, interferon gamma, seems to be critical for social behavior and that a variety of creatures, such as flies, zebrafish, mice and rats, activate interferon gamma responses when they are social. Normally, this molecule is produced by the immune system in response to bacteria, viruses or parasites. Blocking the molecule in mice using genetic modification made regions of the brain hyperactive, causing the mice to become less social. Restoring the molecule restored the brain connectivity and behavior to normal. In a paper outlining their findings, the researchers note the immune molecule plays a “profound role in maintaining proper social function.”...

"The researchers note that a malfunctioning immune system may be responsible for “social deficits in numerous neurological and psychiatric disorders.” But exactly what this might mean for autism and other specific conditions requires further investigation. It is unlikely that any one molecule will be responsible for disease or the key to a cure. The researchers believe that the causes are likely to be much more complex. But the discovery that the immune system – and possibly germs, by extension – can control our interactions raises many exciting avenues for scientists to explore, both in terms of battling neurological disorders and understanding human behavior."...

Kipnis and his team worked closely with UVA’s Department of Pharmacology and with Vladimir Litvak’s group, Ph.D., at the University of Massachusetts Medical School. Litvak’s team developed a computational approach to investigate the complex dialogue between immune signaling and brain function in health and disease.

“Using this approach we predicted a role for interferon gamma, an important cytokine secreted by T lymphocytes, in promoting social brain functions,” Litvak said. “Our findings contribute to a deeper understanding of social dysfunction in neurological disorders, such as autism and schizophrenia, and may open new avenues for therapeutic approaches.”



Yeah Benedetta,

It has been 20 years for me on these particular matters. It is a bit vindicating to see the gut microbiome being tied to CFS now and leaky gut given validity. Yet, those I tried to explain this to then along with all the other aspects. have long dismissed what I said or say. At least wee know and people can be helped.


Thanks Nick for the last two up dates. I don't give zinc, but all the rest - I do.

Interesting about the gut microbes. Finally; after years and year and years -- leaky gut is now in pub med - nih research papers; and no one is making fun of them now. Yeah - now - 20 years later. Geesh.


Chronic fatigue syndrome is in your gut, not your head

"Our work demonstrates that the gut bacterial microbiome in chronic fatigue syndrome patients isn't normal, perhaps leading to gastrointestinal and inflammatory symptoms in victims of the disease," said Maureen Hanson, the Liberty Hyde Bailey Professor in the Department of Molecular Biology and Genetics at Cornell and the paper's senior author. "Furthermore, our detection of a biological abnormality provides further evidence against the ridiculous concept that the disease is psychological in origin."...

"At the same time, the researchers discovered specific markers of inflammation in the blood, likely due to a leaky gut from intestinal problems that allow bacteria to enter the blood, Giloteaux said.

Bacteria in the blood will trigger an immune response, which could worsen symptoms.

The researchers have no evidence to distinguish whether the altered gut microbiome is a cause or a whether it is a consequence of disease, Giloteaux added.

In the future, the research team will look for evidence of viruses and fungi in the gut, to see whether one of these or an association of these along with bacteria may be causing or contributing to the illness."



Hi Benedetta, good to hear from you.

There are a number of things happening and contributing to the whole of the system dysfunction. I have mentioned aldehydes and alcohol/ethanol related genes in the past and Candida's contribution with aldehydes. This next report is long , but very good and it speaks of endogenous and exogenous aldehydes as they may pertain to autism. Getting the yeast under control was very helpful in our case.

The Pivotal Role of Aldehyde Toxicity in Autism Spectrum Disorder: The Therapeutic Potential of Micronutrient Supplementation

Aldehydes generated by gut microbiota
"Gastrointestinal abnormalities are common among those suffering from neurodevelopmental disorders, including ASD. In addition to malabsorption problems in unhealthy intestines, abnormal microbiota of the gut appear to be contributing factors in ASD mouse models28 as well as in humans.29 One suggested explanation is that yeast and bacterial gut flora generate toxins, including alcohols and aldehydes, such as methylg-lyoxal,30 during the metabolism of various carbohydrates. Methylglyoxal is a potent aldehyde implicated in numerous disorders.3 Certainly, Candida infections common in ASD31 have long been suspected of converting carbohydrates into ethanol,32 which is subsequently metabolized to the potent neurotoxin, acetaldehyde. Alterations in the normal gut microflora of mice have also been linked to oxidative stress.33 Research into the microbiota–gut–brain axis in neurodevelopmental disorders is in its earliest stages, but aldehydes may play an important role."...

"Taken together, aldehyde toxicity induces micronutrient deficiencies in sulfur-containing antioxidants, Zn2+, B6, B1, Mg2+, and folate, creating oxidative stress and disruptions in a cascade of metabolic reactions."



You have hit on a lot of great things - almost information overload since I got behind. Sorry.

Vasculitiis of the peripheral small capillaries was a good one article.

You hit upon Parkinson disease along those same lines. I am worried about just that for my son. I am worried about early on set Parkinson. My Father has it, and my son tends toward constipation.

I am making Kimchi right now. I raised the prettiest Nappa cabbage this spring. They have a curly leaf and look like a big green flower. I need to watch his diet a lot more. He is gluten free and casein free, but I am not getting those probiotics and fiber down him like I should. Or vitamins.

In spite of the article that said too many vitamins might be the problem - I would dare say it is the opposite - the gut is not absorbing . But as Jenny says - is that the right kind of vitamin - Folic or folate.

Toxins - metals has an extra electron on the out ring and wants to travel in pairs - was a great article. That is why everything like aluminum and antimony comes out first before mercury. That kind of ties it all together when it comes to the gold salts. Does gold bind with these heavy metals -- the answer is yes. Once attached to gold does it make it easier for the body to get rid of both gold and the heavy metal. I bet it does.

Raynards -- right on-- my neighbor's grand daughter in middle school has Raynards . She is thinking on things - I have pointed out to her that Raynards is a form of vasculiitis just like Kawaskis is.

Lots and lots of great stuff.

Thank You Nick.


Oh, I have missed a lot!

Let me catch up on it all this reading.

You are my friend too Nick and Thus, I love you too.


Where is love. I started this journey based on pure love. I implore those of you supremely educated in love to think in kind.

nick63 @twc.com

Benedetta. I ,love you and wonder at your insight at once. God bless you.


You are wrong. It is a form of autism I am describing. Cord clamping causes, or contributes, to very little autism.


Hope to develop this.

Measles and Nectins...so far Nectin 4 in epithelial cells. This would relate to lower cancer rates in Autism and the microvascular/capillary issues with the angiogenesis recently reported on in some with Autism. Possible Polio virus and flu vaccine ties. It is interesting certain measles virus vaccines are being worked on for certain cancers.


I still don't know if boosted Vitamin D could kink in GC-MAF, though I lean against the idea. What is somewhat convincing is the relationship of the GC protein with other elements perturbed in immune/cell/clock circadian ryhtm function with Autism.


I don't know why the GC protein is not available yet, but Dr. Bradstreet was correct. Is it just Nagalase levels hindering DBP? Whether that is the main issue in D3 not being transported to the receptor what I have used< Olmesartan, accomplishes the task it appears by also being able to activate the VDR. Therefore GC-Maf and Olmesartan would accomplish the same thing.


In the GC Gene card info one of the drugs for the GC gene is acetaminophen..hmmm. The GC gene biological processes also effected are:

female pregnancy IEA
lactation IEA
steroid metabolic process TAS
response to nutrient levels IEA
response to estradiol




Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder.


"Vitamin D is implicated in several aspects of human physiology, and polymorphisms in the vitamin D receptor gene (VDR) are associated with a variety of neuropsychiatric disorders. The aims of this study are to determine whether VDR polymorphisms are associated with autism spectrum disorder (ASD), to examine serum 25-hydroxyvitamin D (25(OH)D) levels in ASD, and to explore whether VDR polymorphisms influence serum 25(OH)D levels. We investigated 480 subjects (237 children with ASD and 243 healthy controls) for the following VDR polymorphisms: TaqI, BsmI, FokI, ApaI, and Cdx2.Within the same samples, 25(OH)D levels were available only for 85 patients and 82 controls. The Cdx-2 variation was shown to deviate from Hardy-Weinberg equilibrium in the controls and was therefore excluded from the study. We found that the frequency of rare FokI TT, TaqI CC, and BsmI AA genotypes differed significantly between children with ASD and the controls (p=0.042, p=0.016, p=0.038, respectively). After correction for multiple testing, only the TaqI CC genotype remained significant. Further analysis using a recessive model showed that rare genotypes of these polymorphisms were significantly higher in patients compared to controls (p=0.045, p=0.005 and p=0.031, respectively). However, no significant association was found between ApaI and ASD. We found serum 25(OH)D levels to be significantly higher in children with ASD (p<0.001) and that the FokI polymorphism had an effect on serum 25(OH)D levels in children with ASD (p=0.041). Additionally, we found the haplotype GTTT (BsmI/TaqI/FokI/ApaI) conferred an increased risk for developing ASD (p=0.022; odds ratio [95% confidence interval]=2.322 [1.105-4.879]). This is the first clinical study evaluating the association between serum 25(OH)D levels and VDR polymorphisms in children with ASD. Our results demonstrated a significant association between TaqI, BsmI, and FokI polymorphisms and ASD and showed for the first time that FokI polymorphisms and haplotype GTTT (BsmI/TaqI/FokI/ApaI) are associated with an increased risk of ASD. Our findings support the hypothesis that 25(OH)D is involved in the pathophysiology of autism and that serum 25(OH)D levels may be affected by FokI polymorphisms in children with ASD. Our results should be considered as preliminary and needs confirmation by future studies."




If I am wrong in the case of other groups with Autism it also may be the gene expression of the VDR is reduced and Vitamin D may levels rise, but not active the VDR. In such a scenario it might be possible that very high D levels could activate the fewer vitamin D receptors.


I had taken a break from all of this and have not considered the possible effect of very high D3 as resolving some of the problem, at least in some cases. In general I have found I am not in the main on Vitamin D supplementation and we do not use it. My wife tested very high in D3 and low in D2 and that was without supplementation. The sulfated vitamin D being required as well as LDL levels might be part of the problem. It also seems pathogen associated inflammation and sterile inflammation aspect may be occurring for many at the same time and this complicates the matter. The blood irradiation might reduce pathogens that provoke inflammation. But, the bigger problem is how the immune system is working and blood irradiation in Autism would likely produce mild benefits for a very brief time.

I don't think the issue is very simple though. Where there is immune dysfunction ate multiple levels, or individuals with additional biological variants, those effecting the gut vs those effecting the vascular or other area D levels and interaction may be more or less pathological and could benefit some areas while hindering others.

This report reflects my feelings about Vitamin D and feel it is probably more often how Vitamin D relates to Autism then viewing it as a long term treatment.

Infant Exposure to Excessive Vitamin D: A Risk Factor for Autism


A variant in some could complicate the issue of whether Vitamin D could be somewhat helpful.

Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants



Interesting posts recently, Visitor!

It's my understanding that gluten has been used in labs to induce vitamin D deficiency. I can see that tying in in certain ways. Is vitamin D's situation in autism similar to what's been found out about thyroid stuff of late, that just because there are circulating blood levels doesn't necessarily mean its being used, or used correctly, taken up by cells/tissues, etc. Because there are other case reports of spontaneous correction of autistic symptoms upon use of clinically higher vitamin D3 levels - whether by accident or on purpose. Might it kick in GcMaf at a certain threshold, or mitigate mis? Am I interpreting this correctly?

How about this? Can any of this be tied together?


Since the angiogenesis in brain vessels in Autism is not verified, though I currently think it is involved in some or many, this association is speculative. I don't know if a lack of GCMAF is a factor in possible angiogenesis in the brain, yet this report seems noteworthy. There is not a lot to go on in this area so far. How GCMAF and MIF interact is of interest.

Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis.


"BACKGROUND: The vitamin D(3)-binding protein (Gc protein)-derived macrophage activating factor (GcMAF) activates tumoricidal macrophages against a variety of cancers indiscriminately. We investigated whether GcMAF also acts as an antiangiogenic factor on endothelial cells.


The effects of GcMAF on angiogenic growth factor-induced cell proliferation, chemotaxis, and tube formation were examined in vitro by using cultured endothelial cells (murine IBE cells, porcine PAE cells, and human umbilical vein endothelial cells [HUVECs]) and in vivo by using a mouse cornea micropocket assay. Blocking monoclonal antibodies to CD36, a receptor for the antiangiogenic factor thrombospondin-1, which is also a possible receptor for GcMAF, were used to investigate the mechanism of GcMAF action.


GcMAF inhibited the endothelial cell proliferation, chemotaxis, and tube formation that were all stimulated by fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor-A, or angiopoietin 2. FGF-2-induced neovascularization in murine cornea was also inhibited by GcMAF. Monoclonal antibodies against murine and human CD36 receptor blocked the antiangiogenic action of GcMAF on the angiogenic factor stimulation of endothelial cell chemotaxis.


In addition to its ability to activate tumoricidal macrophages, GcMAF has direct antiangiogenic effects on endothelial cells independent of tissue origin. The antiangiogenic effects of GcMAF may be mediated through the CD36 receptor."


As far as taking Vitamin d{at least D3} this may be good to note.

"Children with autism often have very high levels of vitamin D3, occasionally toxic levels (and low levels of D2) which may be produced by gut bacteria. We do not recommend administering vitamin D3, which may result in severe hyperactivity, unless the child has had a vitamin D level test."


Macrophage migration inhibitory factor (MIF or MMIF)

"A cytokine recently linked to autism is macrophage migration inhibitory factor (MIF). MIF is a pro-inflammatory immune regulator that is constitutively expressed in brain tissues, and has important influences on neural and endocrine systems. This macrophage migration inhibitory factor cytokine is produced by neuroendocrine and immune tissues. Macrophage migration inhibitory factor possesses glucocorticoid-antagonist properties within the immune system and participates in the regulation of several endocrine circuits.
•Plasma levels of macrophage migration inhibitory factor (MIF) were higher in individuals with autism.
•Individuals with autism with the highest levels of plasma MIF were found to have the most severe behavioral symptoms.
•Macrophage migration inhibitory factor is of critical importance for the host response to microbial infections and in several autoimmune diseases.
•Macrophage migration inhibitory factor expression is usually constitutive at low levels."



While one may or may not have Kawasaki's there is an aspect that can be autoimmune based and as put forward earlier in this thread and may be related to mercury though other pathogens can be the trigger. This, again, associates HMGB1 with a vascular condition though MIF levels in Kawasaki's and those with only Autism show differing values. I can not speculate what the presence of both conditions together would give in MIF levels, but their is a partially shared pathology it appears.

New understanding of autoimmune diseases

"Thanks to a recent Yale study, physicians may soon adopt a new method to combat rheumatoid arthritis and other autoimmune diseases."

"Researchers at the Yale School of Medicine have discovered a transcription factor, ICBP90, that has been shown to regulate the expression levels of MIF — a gene that has been implicated in a number of diseases, primarily autoimmune diseases and cancer. The transcription factor, a protein responsible for facilitating the production of RNA from DNA, binds to MIF’s promoter region, which helps to regulate and initiate transcription. According to the study authors, by identifying the connection between ICBP90 and MIF, researchers can develop new methods of drug treatment for diseases including rheumatoid arthritis and cancer by targeting the gene in a more precise and personalized way."...

"Low expression of MIF has been shown to have benefits against certain diseases. Bucala noted that low expression of MIF confers resistance to death from malaria. Low expression also decreases susceptibility to autoimmune diseases and lessens their severity."...

"There are two potential therapeutic implications of the study, according to Maor Sauler, study co-author and medical school professor. The first will allow researchers to better understand how MIF is involved in disease, particularly in differentiating what is caused by environmental stimuli, and what is caused by the gene. The second implication is that scientists will be able to identify the MIF polymorphism in individual patients. This will help to indicate patients’ susceptibility to autoimmune diseases as well as signal which patients will respond best to anti-MIF or anti-ICBP90 therapy, Sauler added."


High mobility group box 1 (HMGB1) and macrophage migration inhibitory factor (MIF) in Kawasaki disease.



"To investigate whether two proinflammatory cytokines, high mobility group box 1 (HMGB1) and macrophage migration inhibitory factor (MIF) are involved in the development of Kawasaki disease (KD).


Twenty-seven patients with KD were included in this study. Eleven patients with sepsis and 28 healthy children served as controls. Serum levels of HMGB1 and MIF were measured by corresponding enzyme-linked immunosorbent assay (ELISA) kits, respectively. Real-time polymerase chain reaction (PCR) was used to quantify the expression levels of genes encoding receptor for advanced glycation end-products (RAGE), an HMGB1 receptor, and CD74, an MIF receptor in peripheral blood mononuclear cells (PBMCs).


Serum levels of HMGB1 and MIF in KD patients were the highest in the early acute phase and gradually decreased after defervescence. Serum HMGB1 and MIF levels in KD patients were significantly higher than those in controls (HMGB1, p<0.001; MIF, p<0.01). The expression levels of the RAGE gene and CD74 gene in KD patients were significantly higher than those in controls (RAGE, p<0.001; CD74, p<0.01).


These data suggest that HMGB1 and MIF play an important role in immune responses in KD patients."


Macrophage migration inhibitory factor and autism spectrum disorders.



"Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage-activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. On the basis of results of previous genetic linkage studies and reported altered innate immune response in autism spectrum disorder, we hypothesized that MIF could represent a candidate gene for autism spectrum disorder or its diagnostic components.


Genetic association between autism spectrum disorder and MIF was investigated in 2 independent sets of families of probands with autism spectrum disorder, from the United States (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for autism spectrum disorder diagnoses. Genotyping was performed for 2 polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were conducted in a subset of Dutch patients from whom plasma was available.


There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder-related behaviors. Also, probands with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity of multiple autism spectrum disorder symptoms.


These results identify MIF as a possible susceptibility gene for autism spectrum disorder. Additional research is warranted on the precise relationship between MIF and the behavioral components of autism spectrum disorder, the mechanism by which MIF contributes to autism spectrum disorder pathogenesis, and the clinical use of MIF genotyping."


Serum levels of macrophage migration inhibitory factor in children and adolescents with autistic disorders


"Background: There is growing awareness of an immunological involvement in children with autistic disorder (AD). Studies suggest that innate rather than adaptive neuroimmune responses are associated with autism. Macrophage migration inhibitory factor (MIF), being an upstream regulator of innate and adaptive immunity, could play a role in this disorder. Objective: We aimed to study serum levels of MIF in a subset of children with autism and its relation to disease severity and important clinical manifestations of the disease. Methods: The study included 21 children and adolescents diagnosed with AD with a mean age of 6.9± 2.9 years. Patients were neurologically evaluated and categorized into those with mild to moderate autism and those with severe disorder. In addition to assessment of cognitive abilities and electroencephalogram performance, MIF levels were measured in the sera of included patients and were compared to those of a matched control group. Results: Levels of MIF were not significantly different in the patients and the control group. However, serum MIF was significantly reduced in patients with severe AD (z=2.197, P=0.029) compared to those with milder disease. Furthermore, there was a significant negative correlation between MIF levels and the degree of severity of the non-verbal communicative skills (r= -0.49, P=0.042). MIF levels were not different in patients with mental retardation, or abnormal electroencephalogram when compared to the rest of the patients. Conclusion: Our study suggests the presence of immune dysfunction in the form of derangement in serum MIF levels in children with AD. Its levels were specifically decreased in a subset of patients with severe disorder compared to those with mild to moderate disease. Decreased serum levels of MIF in patients with AD seem to be associated with worsening of the nonverbal communicative skills which is one of the disturbed behavioral parameters of AD. Further research is warranted to study the precise relationship of immune derangement and both the etiopathogenesis and the behavioral components of AD and its therapeutic implications."



Microglial activation state seems to be more important than microglial numbers, but reducing the amount of inflammatory microglia would be effective. Endotoxins{LPS], peripheral inflammation {esp gut}, mitochondrial dysfunction, and other factors driving the microglial damage being dealt with would be a more complete{enduring} and health giving solution.

Schizophrenia and Alzheimer’s disease risk linked to brain inflammation



Pivotal advance: inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate.

"Gold compounds such as gold sodium thiomalate (GST) can reduce the symptoms of rheumatoid arthritis (RA), although their mechanism of action is not well defined. As the proinflammatory mediator high mobility group box chromosomal protein 1 (HMGB1) may play a role in the pathogenesis of RA, we have performed in vitro studies to investigate whether GST inhibits HMGB1 release as the basis of its mode of action. Murine RAW 264.7 or human THP-1 macrophage cells were stimulated in culture with agents causing extracellular HMGB1 release, including LPS, IFN-gamma, polyinosinic:polycytidylic acid, IFN-beta, or NO in the presence of GST, ranging from 0 microM to 250 microM. Secretion and intracellular location of HMGB1 were assessed by Western blotting, HMGB1-specific ELISPOT assay, and immunofluorescent staining. In parallel, TNF and IFN-beta levels were analyzed by ELISPOT and/or ELISA. Supernatant NO production was analyzed by the Griess method. At pharmacologically relevant doses, GST inhibited the extracellular release of HMGB1 from activated macrophages and caused the nuclear retention of this protein; in contrast, no effects were observed on the secretion or production of TNF. Release of the key endogenous mediators of HMGB1 translocation, IFN-beta and NO, was inhibited by GST. This inhibition required gold, as sodium thiomalate did not affect the responses measured. Furthermore, gold chloride also inhibited release of HMGB1. Together, these results suggest a new mechanism for the anti-rheumatic effects of gold salts in RA and the potential of drugs, which interfere with intracellular HMGB1 transport mechanisms, as novel agents to treat RA."



Pivotal advance: inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate.



Gold Salts - one type is gold sodium thiomalate, which is mentioned later in this quote, may be effecting angiogenesis in brain blood vessels.

Oxidative stress in angiogenesis and vascular disease

"Angiogenesis, either physiological or pathological, requires initiation by proangiogenic factors, exemplified by vascular endothelial growth factor (VEGF), placental growth factor, platelet-derived growth factor-B, transforming growth factor β, and angiopoietin-1 (ANG-1).2 In most situations, if not all, angiogenesis is closely interwoven with the mobilization of inflammatory cells.5 During physiological or repair processes, such as wound healing, the inflammation process is transient; most pathological conditions, exemplified by cancer, involve a continuous recruitment of inflammatory cells, which, in turn, serve as a substantial source of ROS.6 This functional connection between the inflammation-dependent generation of ROS and angiogenesis plays an important role during various stages of tumor progression, from its initiation stage to vascularization and metastasis. Moreover, in most pathologies, oxidative stress operates as part of a positive feedback mechanism, which gives it even more signification in the process.7

Oxidative stress, which is defined as an imbalance between prooxidant and antioxidant systems,7 can be both a cause and consequence of many vascular complications and serve as one of the biomarkers for these conditions. At the same time, well-controlled oxidative stress may be beneficial for angiogenesis during tissue repair. In this review, we summarize the history and recent findings on the relationship between oxidative stress and angiogenesis, and discuss the implications of oxidative stress on pathological conditions and therapeutic strategies"...

"By 1 electron at a time, oxygen can be sequentially reduced to 4 components: superoxide anion, hydrogen peroxide, hydroxyl radical, and a water molecule.8 During this reduction-oxidation (redox) reaction, ROS are produced as intermediates in vivo. Superoxide anion is known to be a main contributor to the generation of most ROS and a crucial mediator of electron transport chain reactions in mitochondria. Usually, superoxide anion is rapidly removed through dismutation to hydrogen peroxide, either spontaneously or by superoxide dismutases (SOD).8,9 Neutrophil-secreted myeloperoxidase further converts hydrogen peroxide and chloride into highly reactive hypochlorite. For vascular cells, superoxide anion and hydrogen peroxide appear to be particularly important because they are able to activate diverse pathways to induce either new vascular growth, or vascular dysfunction and destruction.10

ROS can be generated by all vascular cell types, including endothelial cells, smooth muscle cells, adventitial fibroblasts, and perivascular adipocytes.11 There are 2 main endogenous sources in the vasculature: mitochondrial electron transport chain reactions and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.11-13 In mitochondria, more than 95% of oxygen consumed by cells is used to yield water molecules through redox reactions.14 Particularly, at complex I and III in the transport chain, premature electron leakage to oxygen occurs, which causes less than 4% of oxygen to be reduced to superoxide anion, but not to water, generating oxidative stress.8,10 NADPH oxidase, an enzyme that generates superoxide anion by transferring electrons from NADPH to oxygen, is recognized as a major source of ROS in many cell types, including endothelial and smooth muscle cells.10,13-17 It is important to note that in many conditions, the respiratory (oxidative) burst of inflammatory cells, such as neutrophils and monocytes, is the main contributing factor to ROS levels in a number of vascular pathologies."...

"ROS act as a double-edged sword in the vasculature because chronically produced or highly concentrated ROS are detrimental for most tissues, whereas transient or low levels of ROS are able to activate signaling pathways that eventually promote regeneration and growth.21,22 Thus, ROS are implicated, either directly or indirectly, in the process of physiological, pathological, and excessive angiogenesis.

One of the early implications of ROS in angiogenesis resulted from the studies using thiol-containing compounds, which were shown to inhibit macrophage-derived proangiogenic activity, as the conditioned medium from gold sodium thiomalate-treated macrophages potently reduced angiogenesis in rat corneas.23,24 Although an effect was somewhat indirect, the follow-up studies from the same group demonstrated that thiol-containing compounds acting as ROS scavengers may inhibit production of angiogenic factors by macrophages."


Evaluation of oxidative stress in autism: defective antioxidant enzymes and increased lipid peroxidation.


"Autism is a neurodevelopmental disorder of childhood with poorly understood etiology and pathology. This pilot study aims to evaluate the levels of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and levels of malondialdehyde (MDA), a marker of lipid peroxidation, in Egyptian autistic children. Autism is a neurodevelopmental disorder of childhood with poorly understood etiology and pathology. The present study included 20 children with autism diagnosed by DSM-IV-TR criteria and Childhood Autism Rating Scale. Controls included 25 age-matched healthy children. Cases were referred to Outpatient Clinic of Children with Special Needs Department, National Research Center, Cairo, Egypt. We compared levels of SOD, GSH-Px, and MDA in children with autism and controls. In children less than 6 years of age, levels of SOD, and GSH-Px were significantly lower in autistic children compared with their controls, while MDA was significantly higher among patients than controls. In children older than 6 years, there was no significant difference in any of these values between cases and controls. We concluded that children with autism are more vulnerable to oxidative stress in the form of increased lipid peroxidation and deficient antioxidant defense mechanism especially at younger children. We highlight that autistic children might benefit from antioxidants supplementation coupled with polyunsaturated fatty acids. Moreover, early assessment of antioxidant status would have better prognosis as it may decrease the oxidative stress before inducing more irreversible brain damage."


Olmesartan may raise superoxide dismutase levels and bear on ros related angiogenesis.


Synergistic Destruction: How Vaccines and GMOs Converge to Fuel Autism and Neurodegenerative Conditions


There is something going on with Superoxide dismutase, microglia, and angiogenesis, still looking at this.


Shinedown - Crow and the Butterfly


Evanescence - Bring Me To Life


The Doobie Brothers - What A Fool Believes



Pregnant Mother’s Gut Microbiome Sets The Stage For Baby’s Future Health

"One finding was particularly noteworthy.

“One of the reviews, by Koleva et al, discusses the studies that reveal that the womb is not sterile and that the microbiota of the child are already developing in utero,” said Dr. Sharon Meropol, associate director for research and evaluation at University Hospitals Rainbow Babies & Children’s Hospital’s Center for Child Health and Policy, in a press release. “This means that not only do we have to consider the microbiome of the child but also that of the mother, and the irony is that some of our modern medical practices, through their effect on these early microbiota, could have unintended consequences, interfering with normal development of children’s immune, metabolic, and neurologic systems.”

According to Meropol, the importance of protecting key steps in the transmission and maintenance of healthy microbiota in pregnant mothers and fetuses is supported by increasing evidence. “Disturbed microbiota could potentially contribute to a wide range of childhood diseases, including allergies, asthma, obesity, and autism-like neurodevelopmental conditions,” said Meropol, who is also assistant professor of pediatrics at Case Western Reserve University School of Medicine."



It is worth considering that given that many vaccines require a healthy gut microbiome to work effectively, or at all, that the reason gut issues are occurring in some autism and other gut related problems is that it is the bodies attempt to prevent heightened immune response to vaccines, or dietary antigens, or simply a result of an already stimulated immune response, acquired from the mother, to disease pathogens reflecting a deregulated immune system or one hypersensitive.


It may be that vaccines are the main catalyst for the increase in many immune related conditions{fibro, CFS, and others}, but the cumulative vaccine effects are leading to a plethora of effected mothers who are now giving birth to children already headed into autism or more children more susceptible to vaccines themselves leading into autism. So, it is not that vaccines are not an issue in most cases, but that it is getting to where immune changes in mothers response to infection additional vaccines{flu shots} and conditioned immune status effecting infants prenatally too is more often than before enough to bring about autism even before an infant receives their vaccines.

If this is the case, it blurs the line in seeing where the insults take place and ignoring immune effects in mothers by vaccines misses the tie to increased autoimmune and inflammatory diseases in the population at large. Because of these effects a child can now be born with autism beyond the limited "gene only" causes.


I have continuously expressed that vaccines are trigger only for some or, so I am clarifying my statement "vaccines lead to autism" in the last post. I realized after reading it again that I always wish to make this distinction.


Pecam1 is not a growth factor, but involved. I did not mean to call it a growth factor.


Vaccines lead to autism and other problems as many at AoA have known. It was no surprise when, after my wife fell, the examining physician noted her slightly blue fingers and nails and proclaimed she had Raynaud's a couple of years ago. My wife's mother also has the condition, but none known in other relatives before. My wife has had this condition since I have known her. I imagine in both women vaccines and other environmental factors led to the condition. Dr. Moulden has stated that Raynaud's is related to some Autism and I believe he was the first to associate it with Autism.

The sometimes comorbid conditions with neuroimmune function disturbance like arthritis, and Raynaud's both have relation to the vascular system and likely certain vascular wall growth factors such as pecam1 end egf and its receptor. If I remember correctly Dr Moulden proposed that the leukocytes become part of the occlusion in micro vessels and lekocyute transmigration and angiogenesis are part of the picture along with red blood cell clumping.

I have tried to use more conventional sources, but this first article is relevant.

Casualties in the War: New Research Confirms Vaccines Do Have a Dark Side

"One chapter calls adjuvants as “the ‘dirty little secret’ of immunologists” because, just like the natural infections they are used to deter, they carry a risk of triggering chronic disease. Scientists knew this at least as far back as 1956 when they induced arthritis in Wistar rats – known as “adjuvant’s disease” in the industry. It’s incredibly ironic that rather than removing them from vaccines immediately, they tailored this “right nuisance” and for six decades now have widely injected adjuvants into animals to create lab models of arthritis, allergies, asthma, lupus and more — so they can test drugs for the diseases that are increasingly plaguing humans injected with adjuvants.

ASIA Syndrome

Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) was first described in the medical literature in 2011 but in reality it just identifies the old phenomenon of vague post-vaccine symptoms including muscle and joint pain, numbness and tingling, weakness and chronic fatigue, which vaccine researchers and physicians have dismissed and ignored, but which actually signify progressive and insidious immune system damage that can take years to manifest into full blown autoimmune disease.

It is probably adjuvants in the heavily vaccinated farmed salmon, say scientists from the University of Padua Italy, reviewing their effects in animals, that frequently cause them to “develop mild to severe pathological changes” including impaired growth, decreased carcass quality, spinal deformities, eye disease and gut inflammation. Who knows what else they would develop if we didn’t eat them first."


In the response to a post at AoA one said:

"Stress will cause aggregation in preparation for clotting in case of injury. Think "fight or flight" - when you are preparing for battle or to run away, there is a significant change you may get hurt. When the the balance of stress hormones is disrupted (shifted) due to high anxiety or panic, the body doesn't differentiate between real or perceived danger and prepares to clot. So thats ONE factor at work.

Heavy metals like lead and mercury (and aluminum which is not technically a "heavy" metal) also damage the circulatory system and lead to problems like Raynaud's Syndrome, atherosclerosis, hypertension, stroke, and aneurysm.

Metals and other toxins have something else in common - a single valence electron in their outermost ring. This makes them very attractive to each other - they don't like to be alone but like to travel in pairs so they will "hook up" with other toxins. This is one reason (along with impaired detoxificatio due to depletion of metallothionein) why our kids, once shot up (pun intended) with aluminum or thimerosal (flu vaccine, rhogam, etc.) become like magnets for other toxins. It's also why when chelating, mercury does not come out until after aluminum, antimony, and lead. The magnets (our children) hold onto the metals because their electrical charges have been altered.

The comment about babesia (a bacteria associated with Lyme disease) is also correct, which is why adults with chronic Lyme exhibit many of the same behavioral and neurological issues as do children with "autism."

Infections in the blood (from systemic yeast, viruses, strep, staph, etc) will also cause clumping, as what is left of the immune system tries to kick in and fight off the infection. Remember that one of the first things the immune system does is to send extra blood (and oxygen) to the sight of injury or infection. This is part of the healing process and is why we get the swelling, heat, and itching when we get a minor cut or scrape. That's the body's attempt to heal.

The problem is, in our children there are so many different things to fight that their bodies become confused and shift over into autoimmunity. The analogy I use is like the old Space Invaders game where you start of shooting at one bad guy and it's relatively easy, but as things speed up, there are too many bad guys to shoot at accurately and you end up crashing and burning."

Marcella Piper-Terry, M.S.


Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations.


"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 neuro-immune 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."



Unless you have followed much of this thread individual reports may mean little, keep in my microglial activastion and cytokine function like TNF and this biphasic action related to angiogenesis, and its dysregulation, can be tied to autism and other neuroimmune conditions and maybe relate to the swings in bipolar and the persiods or contsant psychosis especially when increeased blood flow is occurring and be part of psychosis occurring with autism at times. I am posting a good bit of the report, but the whole is very enlightening.

Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of TNF and TGF-β1



"Studies of cerebral ischemia and other neuroinflammatory states have demonstrated a strong association between new vessel formation and microglial recruitment and activation, raising the possibility that microglia may be involved in promoting angiogenesis. As endothelial cell proliferation is a fundamental early step in angiogenesis, the aim of this study was to test this hypothesis by examining the influence of microglial secreted factors on brain endothelial cell (BEC) proliferation using BrdU incorporation.


Primary cultures of mouse BEC, microglia and astrocytes were used in this study. Proliferation of BEC was examined by BrdU incorporation. ELISA was used to quantify TNF and TGF-β1 levels within cell culture supernatants.


Microglia regulated BEC proliferation in a biphasic manner; microglia conditioned medium (MG-CM) from resting microglia inhibited, while that from activated microglia promoted BEC proliferation. A screen of microglial cytokines revealed that BEC proliferation was inhibited by TGF-β1, but promoted by TNF. ELISA showed that TNF and TGF-β1 were both present in MG-CM, and that while TGF-β1 dominated in resting MG-CM, TNF levels were massively increased in activated MG-CM, shifting the balance in favor of TNF. Antibody-blocking studies revealed that the influence of MG-CM to inhibit or promote BEC proliferation was largely attributable to the cytokines TGF-β1 and TNF, respectively.


This data suggests that microglial activation state might be an important determinant of cerebral angiogenesis; inhibiting BEC proliferation and neovascularization in the normal central nervous system (CNS), but stimulating the growth of new capillaries under neuroinflammatory conditions.


Angiogenesis occurs in the central nervous system (CNS) not just during development [1], but also in pathological conditions, including cerebral ischemia [2], neoplasia [3], and neuroinflammation [4,5]. An improved understanding of the factors that control cerebral angiogenesis would be a big step forward in our attempts to regulate angiogenesis for therapeutic means, either to increase blood vessel growth during cerebral ischemia, or to inhibit vessel growth during neoplasia. Angiogenesis is regulated by a plethora of factors, including growth factors [6], cytokines [7], and extracellular matrix (ECM) molecules [8]. Within the CNS, it has been established that hypoxia promotes angiogenesis by at least two separate pathways. One involves hypoxia inducible factor-1α (HIF-1α)-dependent vascular endothelial growth factor (VEGF) release [9], and the other, that involves a HIF-1α-independent COX-2-dependent stimulation of PGE2, leading to angiopoietin-2 release [10]. In addition to soluble factors, ECM proteins also provide important instructional cues in angiogenesis [11], and recent work from our laboratory showing that fibronectin is strongly induced on angiogenic capillaries in the hypoxic CNS [12], as well as on angiogenic vessels in the developing CNS [13], suggests that this protein may also be important for cerebral angiogenesis.

In the normal adult CNS, brain endothelial cells (BEC) occupy an angiostatic state, and have the impermeable, tight-barrier characteristics of mature cerebral endothelium [14]. During cerebral ischemia and other neuroinflammatory conditions, vessels in the adult CNS mount an angiogenic response in which BEC proliferate to form new capillary sprouts [15,16]. Interestingly, studies of cerebral ischemic tissue have demonstrated a strong association between new vessel formation and microglial recruitment and activation [17,18], raising the possibility that microglia, the principal immune effector cells in the CNS, may actively promote angiogenesis. As endothelial cell proliferation is a fundamental early step in the angiogenic response, the aim of this study was to test this hypothesis by examining the influence of microglial secreted factors on BEC proliferation."


Heightened blood flow in the brain linked to development of psychosis

"Using a Magnetic Resonance Imaging (MRI) technique they found that 52 young people deemed to be at ultra high risk of psychosis had increased or 'hyperactive'levels of blood flow compared to 27 healthy controls in the hippocampus, striatum and midbrain - all brain regions that are particularly implicated in the onset of psychotic disorders like schizophrenia.

This study is one of the first in humans to confirm results from animal research, which has already shown that increased activity in these brain regions drives the development of psychosis.

In the study, published today in the American Journal of Psychiatry and funded by the Medical Research Council, the researchers also repeated the MRI scans after 18 months to examine how blood flow levels had changed. In participants whose presenting symptoms had resolved, the researchers found that resting blood flow levels in the hippocampus had decreased to the levels seen in healthy participants. This suggests that normalisation of blood flow in the hippocampus may underlie clinical improvement in these participants.

Professor Paul Allen from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London and the University of Roehampton said: 'Our research identified significant differences in brain blood flow between healthy people and those at ultra high risk of psychosis. These differences help us understand the neurobiological mechanisms that underlie the development of psychosis.'"



The angiogenesis relating to Autism is only preliminary in the study, so how this may have similar origins and effects in different conditions regarding angiogenesis is not clear.

It is reasonable to think the processes is similar in angiogenesis in RA, Parkinson's, and Autism and maybe in general.

Targeting angiogenesis in Parkinson’s disease

"Movement and balance disorders are a well-known consequence of Parkinson’s disease (PD). Hypothesizing that these features could be related to the formation of new blood vessels, a study published in Neurology assessed the presence of biomarkers of new blood vessel formation (angiogenesis) in the cerebrospinal fluid of patients with PD, and compared it with blood-brain barrier permeability, white matter lesions, and cerebral microbleeds. This study initially used samples from 100 PD patients and was followed by two additional validation groups of 87 patients with PD with dementia 93 patients with PD with and without dementia.

The findings showed that there is indeed a connection between the presence of markers of angiogenesis in the brain and the motor and balance impairments of PD patients. Increased angiogenesis was also linked to an increased permeability of the blood-brain barrier, to white matter lesions, and to cerebral microbleeds. These results indicate that medication for angiogenesis may be an additional and promising therapy for PD patients in the future."


The role of High-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on Vascular endothelial growth factor.



"High-mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to better define the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis.


Balb/c mice were injected with monoclonal anti-collagen antibody cocktail followed by lipopolysaccharide to induce arthritis.


HMGB1 and VEGF were over-expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or of VEGF alternatively resulted in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up-regulation and increased synovial angiogenesis. The selective inhibition of VEGF resulted in no induction of arthritis also in mice receiving exogenous HMGB1. Cytokine ELISA analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of IL-1β , IL-6 and TNF-α in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL-17A concentration.


The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The pro-inflammatory and pro-angiogenic cytokine IL-17A is increased when HMGB1 is inhibited, but the synovial angiogenesis is nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA-like model."




Fasting has been suggested to have some bearing on certain conditions like epilepsy, tumors, and stroke and possibly Alzheimer's and maybe Parkinson's and seizures. There is very little explicit literature I have found about fasting and these conditions. The relation to diet or fasting and angiogenesis may be found in relation to carbohydrates relating to advanced glycation end products. These interact with HMGB1 and HMGB1 does bear on inflammation and angiogenesis. This is an area I am working on presently. I am looking at leptin, glucose, and insulin in this area as well and fasting has some relation here too.


Have you looked at all into connections on the effects of fasting on angiogenesis and effects on the brain?


My wife had developed arthritis and Olmesartan, in combination with the dietary changes effecting the gut microbiome has arrested and even reversed the condition to a degree. Angiogenesis is implicated in some arthritis, so it all fits. It explains the inflamed and notable capillaries in her ears too I believe. It is has to to have been happening in her brain as well.

The codependence of angiogenesis and chronic inflammation.


"Angiogenesis is the growth of new blood vessels from existing ones. It is an important aspect of new tissue development, growth, and tissue repair. It is also a component of many diseases including cancer, blindness, and chronic inflammation such as rheumatoid arthritis (RA) and psoriasis. There is considerable evidence to suggest that angiogenesis and chronic inflammation are codependent; recent studies have begun to reveal the nature of this link, which involves both augmentation of cellular infiltration and proliferation and overlapping roles of regulatory growth factors and cytokines. Through these studies, we have begun to understand the codependence of chronic inflammation and angiogenesis, the potential benefits of targeting angiogenesis in the treatment of chronic inflammation, and of targeting chronic inflammation to affect angiogenesis."


Relationship between angiogenesis and inflammation in experimental arthritis.


Background. Angiogenesis is involved in rheumatoid arthritis (RA) leading to leucocyte recruitment and inflammation in the synovium. Furthermore, synovial inflammation itself further potentiates endothelial proliferation and angiogenesis. In this study, we aimed at evaluating the reciprocical relationship between synovial inflammation and angiogenesis in a RA model, namely collagen-induced arthritis (CIA). Methods. CIA was induced by immunization of DBA/1 mice with collagen type II in adjuvant. Endothelial cells were detected using a GSL-1 lectin-specific immunohistochemical staining on knee joint sections. Angiogenesis, clinical scores and histological signs of arthritis were evaluated from the induction of CIA until the end of the experiment. Angiogenesis was quantified by counting both the isolated endothelial cells and vessels stained on each section. To evaluate the effect of increased angiogenesis on CIA, VEGF gene transfer was performed using an adeno-associated virus encoding VEGF (AAV-VEGF), by intra-muscular or intra-articular injection in mice with CIA. Results. We showed an increase in synovial angiogenesis from day 6 to day 55 after CIA induction, and, moreover, joint vascularization and clinical scores of arthritis were correlated (p < 0.0001, r = 0.61). Vascularization and histological scores were also correlated (p = 0.0006, r = 0.51). Systemic VEGF overexpression in mice with CIA was followed by an aggravation of arthritis as compared to AAV-lacZ control group (p < 0.0001). In contrast, there was no difference in clinical scores between control mice and mice injected within the knee with AAV-VEGF, even if joint vascularization was higher in this group than in all other groups (p = 0,05 versus non-injected group). Intra-articular AAV-VEGF injections induced more severe signs of histological inflammation and bone destruction than AAV-Lac Z or no injection. Conclusion. Angiogenesis and joint inflammation evolve in parallel during collagen-induced arthritis. Furthermore, this work shows that exogenous VEGF can aggravate CIA. It is direct evidence that the increase in joint vascularization leads to an exacerbation of arthritis. Taken together, these results emphasize the role of angiogenesis in inflammatory arthritis. It also suggests an early involvement of angiogenesis in joint inflammation.


Angiotensin Receptor Blockade Modulates NFκB and STAT3 Signaling and Inhibits Glial Activation and Neuroinflammation Better than Angiotensin-Converting Enzyme Inhibition.


"Neuroinflammation, sustained by astroglial and microglial activation, is the preceding event in neurodegeneration. Various clinical reports showed better neuroprotection by AT1 receptor blockade (ARB) than angiotensin-converting enzyme inhibition (ACEi), but experimental evidences and associated mechanism for this observation are lacking. Therefore, we investigated the effect of ARB, using Candesartan, and ACEi, using Perindopril, in equimolar concentrations in astroglial (C6) and microglial (BV2) cells employing lipopolysaccharide (LPS) to induce neuroinflammation. Further, Candesartan (0.1 mg/kg) and Perindopril (0.1 mg/kg) were orally administered in male SD rats for five consecutive days, and on the fifth day, rats were challenged with LPS (i.p.; 250 μg/kg) and sacrificed after 24 h. LPS-induced neuroinflammation (increased astroglial and microglial activation, IκBα degradation, NFкB nuclear translocation, STAT3 activation, and TNF-α release) was more efficiently prevented by Candesartan (even at lower concentration of 1 nM) than by Perindopril (1 μM) in both the cell types and in rat model of neuroinflammation. In addition, increased AT1 receptor (AT1R) and decreased AT2 receptor (AT2R) expression was observed in LPS-induced neuroinflammation in both in vitro and in vivo studies. Candesartan, as compared to Perindopril, increased the expression of AT2R in both the experimental conditions. Interestingly, concomitant blockade of AT2R by PD123319 significantly reversed the beneficial effects of Candesartan in both the cell types and in rat model of neuroinflammation. Finally, our data emphasize that superiority of Candesartan as compared to Perindopril is due to better activation of AT2R which results in PP2A activation, IκBα stabilization, and suppression of NFкB and STAT3 inflammatory signaling."




The RAS system is involved in all sorts of development including ovarian and placental. It is also involved in retinal issues. I think I remember you saying your husband had some sort of eye condition. Am I remembering correctly? It is starting to look like the RAS may be a substantial part of the picture. The Aldosterone component is implicated too so I would include it as well. RAAS = renin-angiotensin-aldosterone system.


My uncle had a blocked blood vessel to his heart and so he grew another one all on his own.

Sounds like the same thing going on here too.


The continued angiogenesis mentioned two posts back seems to indicate that it is persistent though no reasons for this condition are stated. If Olmesartan down blocks AT1 receptors it may reduce angiogenesis and it may also increase activation of angiotensin AT2 and AT4 receptors that "trigger brain anti-ischemic mechanisms by favouring cerebral blood flow (angiogenesis and recruitment of pre-existing collateral circulation, specifically in the ischemic brain where AT2 receptors are overexpressed) or by directly increasing neuronal resistance to anoxia."

Angiotensin AT1-receptor blockers and cerebrovascular protection: do they actually have a cutting edge over angiotensin-converting enzyme inhibitors?


"First, an update of the vascular systemic and tissue renin-angiotensin-aldosterone system is provided to explain how it is regulated at the systemic and tissue levels, and how many angiotensin peptides and receptors can be modulated by the various antihypertensive drugs. Second, experimental data is presented to support the hypothesis that antihypertensive drugs that increase angiotensin II formation, such as diuretics, AT1-receptor blockers and dihydropyridines, may have greater brain anti-ischemic effects than antihypertensive drugs that decrease angiotensin II formation, such as beta-blockers and angiotensin-converting enzyme inhibitors, because they increase activation of angiotensin AT2 and AT4 receptors. Indeed, these trigger brain anti-ischemic mechanisms by favouring cerebral blood flow (angiogenesis and recruitment of pre-existing collateral circulation, specifically in the ischemic brain where AT2 receptors are overexpressed) or by directly increasing neuronal resistance to anoxia."

Reduced angiogenesis and delay in wound healing in angiotensin II type 1a receptor-deficient mice


"Angiotensin II (Ang II) is a bioactive peptide that plays important roles in blood pressure regulation and salt–water homeostasis. Recently, Ang II was reported to function in the promotion of angiogenesis. Since the wound healing process is highly dependent upon angiogenesis, we employed Ang II receptor knockout mice (AT1a−/−) to investigate whether or not Ang II facilitates angiogenesis and wound healing via AT1a receptor signaling. In comparison to wild-type (WT) mice, wound healing and wound-induced angiogenesis were significantly suppressed in AT1a−/− mice, and these mice exhibited reduced expression of CD31 in wound granulation tissues. In comparison to vehicle-treated mice, wound healing was delayed significantly in mice treated with an AT1-R antagonist and this delay was accompanied by the reduced expression of vascular endothelial growth factor in wound granulation tissues. These findings suggest that Ang II–AT1a signaling plays a crucial role in wound healing and wound-induced angiogenesis."


There are some disconnects in how reducing angiogenesis may be therapeutic at the same time reducing wound healing, but this remains to be understood.


I o9mmitted a link when I said this:

Please read beyond the abstact and click on "look inside" in the top blue bar"
It is here.

Regulation of Angiogenesis by Angiotensin II



If you have followed this thread you will have seen how I have emphasized the Angiotensin system. The relation of hypoxic. inflammatory, and ischemic events effecting the brain and its vasculature is beginning to be grasped as it relates to Autism and it appears Schizophrenia. Vaccines upregulating or causing these effects, particularly in what seems to be increasing amounts of infants with preexisting or hypersensitive inflammatory profiles would point to greater amounts of vaccine effects in these pathologies of the vasculature. This is a report I for which I have been hoping. Olmesartan...?

Please read beyond the abstact and click on "look inside" in the top blue bar. Neovascularization is a mechanism of wound response and attempt at healing, increasing blood supply, and oxygen supply. B6 levels increase after surgical wounds and b6 levels are often related to Autism. Wounded children.

Scientists find new vessel for detecting autism

"Evidence of autism may be found in the composition and malfunction of the brain's blood vessels, a team of scientists has found. Their research sheds new light on the causes of autism, which previously had pointed to neurological make-up rather than to the vascular system, and identifies a new target for potential therapeutic intervention.

"Our findings show that those afflicted with autism have unstable blood vessels, disrupting proper delivery of blood to the brain," explains Efrain Azmitia, a professor in NYU's Department of Biology and the study's senior author.

The study, "Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum," appears in the Journal of Autism and Developmental Disorders. Its other co-authors were: Zachary Saccomano, an NYU graduate student; Mohammed Alzoobaee, an NYU undergraduate at the time of the study; Maura Boldrini, a research scientist in the Department of Psychiatry at Columbia University; and Patricia Whitaker-Azmitia, a professor in the Department of Psychology and director of the Graduate Program in Integrative Neurosciences at Stony Brook University.

"In a typical brain, blood vessels are stable, thereby ensuring a stable distribution of blood," adds Azmitia, also an adjunct professor at NYU School of Medicine's Department of Psychiatry. "Whereas in the autism brain, the cellular structure of blood vessels continually fluctuates, which results in circulation that is fluctuating and, ultimately, neurologically limiting."

In their study, the researchers examined human postmortem brain tissue—some from normal brains and others from those with an autism diagnosis. In the microscopic analysis, the scientists were blind to the nature of the tissue, not knowing if it came from an autistic brain or a typical one.

Their cellular studies uncovered angiogenesis—the creation of new blood vessels—in the autistic brain tissue, but not in that of typical brains. The distinction is a significant one—evidence of angiogenesis indicates that these vessels are repeatedly being formed and in constant flux, underscoring an instability in the blood's delivery mechanism. Specifically, in autistic brains, they found increased levels of the proteins nestin and CD34—molecular markers of angiogenesis—compared to typical brains.

"We found that angiogenesis is correlated with more neurogenesis in other brain diseases, therefore there is the possibility that a change in brain vasculature in autism means a change in cell proliferation or maturation, or survival, and brain plasticity in general. These changes could potentially affect brain networks," Boldrini noted.

"It's clear that there are changes in brain vascularization in autistic individuals from two to 20 years that are not seen in normally developing individuals past the age of two years," observes Azmitia. "Now that we know this, we have new ways of looking at this disorder and, hopefully with this new knowledge, novel and more effective ways to address it."


Angiotensin converting enzyme activity is positively associated with IL-17a levels in patients with schizophrenia.


"Previous studies of our group showed increased plasmatic Angiotensin-I Converting Enzyme (ACE) activity in schizophrenia (SCZ) patients compared to healthy controls, which was also associated to poor cognitive functioning. The ACE main product angiotensin II (Ang-II) has pro-inflammatory properties. Activated immune-inflammatory responses in SCZ and their association with disease progression and cognitive impairments are also well-described. Therefore, we examined here the association of plasma ACE activity and inflammatory mediators in 33 SCZ patients and 92 healthy controls. Non-parametric correlations were used to investigate the association of the enzyme activity and the peripheral levels of immune inflammatory markers as interleukins, tumor necrosis factor (TNF-α), and interferon (IFN-γ). Although no significant correlations could be observed for ACE activity and measured cytokines levels in healthy controls, a significant positive correlation for ACE enzymatic activity and IL-17a levels was observed in SCZ patients. Correcting for gender did not change these results. Moreover, a significant association for ACE activity and IFN-γ levels was also observed. To our knowledge, this is the first study to show a significant association between higher ACE activity and the levels of cytokines, namely IL-17a and IFN-γ, in patients with SCZ."


Increased serum Osteopontin levels in autistic children: Relation to the disease severity.


“Autoimmunity to brain may play an etiopathogenic role in autism. Osteopontin is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. Osteopontin induces IL-17 production by T-helper 17 lymphocytes, the key players in the pathogenesis of autoimmune disorders. Anti-osteopontin treatment reduces the clinical severity of some autoimmune neuroinflammatory diseases by reducing IL-17 production. We are the first to measure serum osteopontin levels, by ELISA, in 42 autistic children in comparison to 42 healthy-matched children. The relationship between serum osteopontin levels and the severity of autism, which was assessed by using the Childhood Autism Rating Scale (CARS), was also studied. Autistic children had significantly higher serum osteopontin levels than healthy controls."


Osteopontin - Wiki

"Stimulation of OPN expression also occurs upon exposure of cells to pro-inflammatory cytokines,[31] classical mediators of acute inflammation (e.g. tumour necrosis factor α [TNFα], infterleukin-1β [IL-1β]), angiotensin II, transforming growth factor β (TGFβ) and parathyroid hormone (PTH),[32][33] although a detailed mechanistic understanding of these regulatory pathways are not yet known. Hyperglycemia and hypoxia are also known to increase OPN expression."



As an addition to the last post here is another related article addressing causes of Ovarian issues including Polycystic Ovarian Disease. I had posted in this thread in 2012. It adds a larger perspective that the you tube in the last post.

Environmental toxicants causing ovarian disease across generations

"WSU reproductive biologist Michael Skinner and his laboratory colleagues, including Eric Nilsson and Carlos Guerrero-Bosagna, looked at how fungicide, pesticide, plastic, dioxin and hydrocarbon mixtures affected a gestating rat's progeny for multiple generations. They saw subsequent generations inherit ovarian disease by "epigenetic transgenerational inheritance."

Epigenetics regulates how genes are turned on and off in tissues and cells. Three generations were affected, showing fewer ovarian follicles -- the source of eggs -- and increased polycystic ovarian disease.

The findings suggest ancestral environmental exposures and epigenetics may be a significant added factor in the development of ovarian disease, Skinner said.

"What your great grandmother was exposed to when she was pregnant may promote ovarian disease in you, and you're going to pass it on to your grandchildren," he said. "Ovarian disease has been increasing over the past few decades to affect more than 10 percent of the human female population, and environmental epigenetics may provide a reason for this increase....

The new study, Skinner said, provides a proof of concept that ancestral environmental exposures and environmental epigenetics promote ovarian disease and can be used to further diagnose exposure to toxicants and their subsequent health impacts. It also opens the door to using epigenetic molecular markers to diagnose ovarian disease before it occurs so new therapies could be developed.

In a broader sense, the study shows how epigenetics can have a significant role in disease development and life itself."


All the increased risks for autism from modern inventions, but no real increase in autism?


Glyphosate makes the list.

The 3 Causes of Polycystic Ovarian Syndrome (PCOS) and High Androgens


A New Autism Risk Factor: Moms with Polycystic Ovaries



A couple of weeks back I posted this: "There is a lot unknown about the mitochondrial relation with NLRP3. I theorize a relation between NLRP3, NEk7,and microtubule formation and that this bears on neuronal plasticity and function. I have not gotten very far yet."

Today I found what is supposed to be a new finding about Nek7 and its relation to NLRP3. I had already believed this was the case, but I can't test what I find. I am encouraged and will pursue a relationship to microtubules.

Enzyme involved in cell division also plays a role in inflammation

"DALLAS - Dec. 7, 2015 - UT Southwestern Medical Center and California researchers today provide the first report that an enzyme previously known solely for its role in cell division also acts as an on-off switch in the innate immune system -- the body's first defense against infection.

The identification of the NEK7 enzyme's switch-like activity in immunity could lead to new treatments for a variety of medical conditions linked to inflammation via the NRLP3 inflammasome pathway, including certain metabolic disorders, influenza A, gout, atherosclerosis, and possibly some forms of cancer. The current study investigated mouse models of inflammatory bowel disease and multiple sclerosis.

"NRLP3 is one of several inflammasomes - multiprotein structures in disease-fighting white blood cells - the first of which was identified less than 15 years ago. The NRLP3 complex responds to microbes and other danger signals by activating molecules called cytokines, such as interleukin-1 beta, which trigger inflammation to fight infection," said Nobel Laureate Dr. Bruce Beutler, Director of the Center for the Genetics of Host Defense at UT Southwestern and senior author of the study published online in Nature Immunology"...

The researchers genetically screened thousands of mice and conducted exhaustive interdisciplinary experiments: identifying a defect in inflammasome function, ascribing that defect to a mutation in the gene for the NEK7 enzyme, and fully characterizing NEK7 function in innate immunity.

The enzyme was previously known only for its involvement in cell division, or mitosis, a process that involves the creation of two daughter cells from one parental cell. Specifically, mitosis is the phase of cell division in which the nucleus, which holds all of the cell's genetic material, divides to form two new cells, each with a full complement of genes.

"Our work has shown that the inflammasome cannot become activated during mitosis. This is possibly a protective mechanism that prevents damage to DNA during this part of the cell cycle," said Dr. Beutler, who shared the 2011 Nobel Prize in Physiology or Medicine for his groundbreaking work on innate immunity. Dr. Beutler, a Texas Regental Professor, also holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr."


My odds and ends posts might be delayed.


A couple of weeks back I posted this: "There is a lot unknown about the mitochondrial relation with NLRP3. I theorize a relation between NLRP3, NEk7,and microtubule formation and that this bears on neuronal plasticity and function. I have not gotten very far yet."

Today I found what is supposed to be news about Nek7 and NLRP3. I am encouraged and will see if the there is a relationship to microtubules.

Enzyme involved in cell division also plays a role in inflammation

"DALLAS - Dec. 7, 2015 - UT Southwestern Medical Center and California researchers today provide the first report that an enzyme previously known solely for its role in cell division also acts as an on-off switch in the innate immune system -- the body's first defense against infection.

The identification of the NEK7 enzyme's switch-like activity in immunity could lead to new treatments for a variety of medical conditions linked to inflammation via the NRLP3 inflammasome pathway, including certain metabolic disorders, influenza A, gout, atherosclerosis, and possibly some forms of cancer. The current study investigated mouse models of inflammatory bowel disease and multiple sclerosis.

"NRLP3 is one of several inflammasomes - multiprotein structures in disease-fighting white blood cells - the first of which was identified less than 15 years ago. The NRLP3 complex responds to microbes and other danger signals by activating molecules called cytokines, such as interleukin-1 beta, which trigger inflammation to fight infection," said Nobel Laureate Dr. Bruce Beutler, Director of the Center for the Genetics of Host Defense at UT Southwestern and senior author of the study published online in Nature Immunology"...

The researchers genetically screened thousands of mice and conducted exhaustive interdisciplinary experiments: identifying a defect in inflammasome function, ascribing that defect to a mutation in the gene for the NEK7 enzyme, and fully characterizing NEK7 function in innate immunity.

The enzyme was previously known only for its involvement in cell division, or mitosis, a process that involves the creation of two daughter cells from one parental cell. Specifically, mitosis is the phase of cell division in which the nucleus, which holds all of the cell's genetic material, divides to form two new cells, each with a full complement of genes.

"Our work has shown that the inflammasome cannot become activated during mitosis. This is possibly a protective mechanism that prevents damage to DNA during this part of the cell cycle," said Dr. Beutler, who shared the 2011 Nobel Prize in Physiology or Medicine for his groundbreaking work on innate immunity. Dr. Beutler, a Texas Regental Professor, also holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr."


My odds and ends posts might be delayed.


A few old odds and ends with this post and a couple of the next to follow. A credentialed source by the way.

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia.


"Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R(2)=0.34-0.55, p⩽0.0001; controls R(2)=0.05-0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p⩽0.001-0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature."

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS: Arachnoid membrane; Autism; Bipolar disorder; Blood–brain barrier; Choroid plexus; Endothelial; Epithelial; Gastrointestinal; Psychoses




What you said makes sense and some things we are encountering with good intent are a problem for many. The same way ramping up the immune system in little ones can change the microbiota in the gut and then further effect the immune system and gut/brain axis, though it is hard to know this is the sequence or if it is reciprocal process all along with the gut immunity and the immune system peripheral to it being disturbed together.

It seems in the regressive Autism the effect of the vaccine, whnen involved, acts fairly quickly and tends to support the idea that the immune stimulation/inflammatory response leads to the gut microbiota changes being made. It also seems some increased products from certain bacteria like propionic acid, while causing other problems, are the attempt to prevent even worse colonization and even keep fungal numbers in check. So while dysbiosis creates problems it seems even this represent some helpful elements.


Hi Visitor: was looking back at some of your recent posts - I can see you mentioned folic acid early in November. I do think the synthetic version folic acid is not a good thing, that brains would need folate in the natural plant form and that the synthetic version might displace what little there is of the real stuff in a pregnant mum and I don't think manmade vitamins can ever do exactly the same thing that human development evolved with over the course of history.
There is a group called Vitamin Angels, a non profit pushing vitamins over in undeveloped countries to "help" them. I sent them information several months ago re: the potential issue with folic acid, since most of their "partners" use folic acid in their vitamins, hoping to get their attention. No response. Those poor people in those countries who think they are recipients of only good charity are destined to be victims of the same tragedy American children and pregnant women have gone through, a combination of synthetic folic acid and forced vaccines. So sad.


About three post back I mentioned microtubule formation, as in stability. The following link speaks about a theory, concerning microtubules, I have followed for a long time and thought it had merit. This is a jump ahead, maybe in a primary way, in terms of process about what I have posted, but for those who wonder about the biomedical disruptions in the "soft machine" relating to consciousness this may be intriguing, and for now is a bit of a frontier marker for me.

Discovery of quantum vibrations in 'microtubules' inside brain neurons supports controversial theory of consciousness

"A review and update of a controversial 20-year-old theory of consciousness published in Physics of Life Reviews claims that consciousness derives from deeper level, finer scale activities inside brain neurons. The recent discovery of quantum vibrations in "microtubules" inside brain neurons corroborates this theory, according to review authors Stuart Hameroff and Sir Roger Penrose. They suggest that EEG rhythms (brain waves) also derive from deeper level microtubule vibrations, and that from a practical standpoint, treating brain microtubule vibrations could benefit a host of mental, neurological, and cognitive conditions.

The theory, called "orchestrated objective reduction" ('Orch OR'), was first put forward in the mid-1990s by eminent mathematical physicist Sir Roger Penrose, FRS, Mathematical Institute and Wadham College, University of Oxford, and prominent anesthesiologist Stuart Hameroff, MD, Anesthesiology, Psychology and Center for Consciousness Studies, The University of Arizona, Tucson. They suggested that quantum vibrational computations in microtubules were "orchestrated" ("Orch") by synaptic inputs and memory stored in microtubules, and terminated by Penrose "objective reduction" ('OR'), hence "Orch OR." Microtubules are major components of the cell structural skeleton.

Orch OR was harshly criticized from its inception, as the brain was considered too "warm, wet, and noisy" for seemingly delicate quantum processes.. However, evidence has now shown warm quantum coherence in plant photosynthesis, bird brain navigation, our sense of smell, and brain microtubules. The recent discovery of warm temperature quantum vibrations in microtubules inside brain neurons by the research group led by Anirban Bandyopadhyay, PhD, at the National Institute of Material Sciences in Tsukuba, Japan (and now at MIT), corroborates the pair's theory and suggests that EEG rhythms also derive from deeper level microtubule vibrations. In addition, work from the laboratory of Roderick G. Eckenhoff, MD, at the University of Pennsylvania, suggests that anesthesia, which selectively erases consciousness while sparing non-conscious brain activities, acts via microtubules in brain neurons.

"The origin of consciousness reflects our place in the universe, the nature of our existence. Did consciousness evolve from complex computations among brain neurons, as most scientists assert? Or has consciousness, in some sense, been here all along, as spiritual approaches maintain?" ask Hameroff and Penrose in the current review. "This opens a potential Pandora's Box, but our theory accommodates both these views, suggesting consciousness derives from quantum vibrations in microtubules, protein polymers inside brain neurons, which both govern neuronal and synaptic function, and connect brain processes to self-organizing processes in the fine scale, 'proto-conscious' quantum structure of reality."

After 20 years of skeptical criticism, "the evidence now clearly supports Orch OR," continue Hameroff and Penrose. "Our new paper updates the evidence, clarifies Orch OR quantum bits, or "qubits," as helical pathways in microtubule lattices, rebuts critics, and reviews 20 testable predictions of Orch OR published in 1998 -- of these, six are confirmed and none refuted..."



The first report does not mention effects on other neurons, but you have to think...

Aluminum Activates PERK-EIF2α Signaling and Inflammatory Proteins in Human Neuroblastoma SH-SY5Y Cells.


"Aluminum is the third most abundant element present in the earth's crust and human exposure to it is possible due to industrialization, utensils, medicines, antiperspirants, etc. Evidences suggest involvement of aluminum in a variety of neurodegenerative disorders including Alzheimer's disease. Endoplasmic reticulum (ER) stress has been implicated in various neurological disorders. ER stress may be a result of impaired calcium homeostasis due to perturbed redox balance and is known to elicit inflammation through the activation of unfolded protein response (UPR). In the present study, we aimed to investigate the role of aluminum in ER stress-mediated activation of inflammatory responses in neuroblastoma cells. Lactate dehydrogenase (LDH) release assay revealed that aluminum compromised the membrane integrity of neuroblastoma cells, probably due to membrane damage, as indicated by enhanced levels of lipid peroxidation (LPO). Besides this, our results clearly demonstrated elevated reactive oxygen species (ROS) levels and a weakened antioxidant defence system manifested by decrease in catalase (CAT) activity and cellular glutathione (GSH). Moreover, we studied the expression of key apoptosis-related proteins, ER stress-mediated activation of UPR, and its downstream inflammatory pathway. It was observed that aluminum potentially enhanced protein levels of PERK, EIF2α, caspase 9, caspase 3, and inflammatory markers like NF-κB, NLRP3, HMGB1, and nitric oxide (NO). Furthermore, aluminum altered TNFα, IL1β, IL6, and IL10 mRNA levels as well. The overall findings indicated that aluminum mediates UPR activation through ER stress, which results in induction of inflammatory pathway and apoptotic proteins in neuronal cells."


HMGB1 levels may be already be higher in those susceptible to vaccine injury and this would tie increased autoimmune and inflammatory conditions in the population to the increase in Autism as reports have found HMGB1 levels elevated in those with Autism. HMGB1 acts as an adjuvant itself and the trigger of the vaccine{esp. aluminum} may moderately to precipitously raise inflammation and include effects on neuronal migration and plasticity involving NLRP3 as previously addressed. Severe reactions could kill and show as a child with a severely inflamed body and brain.
Mothers and grandmothers may be having increased epigenetic and immune effects that are predisposing their offspring.

Hep B below


Microglia Control Synapse Number in Multiple Disease States


HMGB1 and Cord Blood: Its Role as Immuno-Adjuvant Factor in Innate Immunity



Likely part of Dr. Bradstreet's venue and related to NLRP3.

NLRP3 inflammasome and its inhibitors: a review

"Cannabinoid receptor 2 (CB2R) is an already demonstrated therapeutic target in inflammation-related diseases (Smoum et al., 2015). Work from our own laboratory (Shao et al., 2014) has shown that autophagy induction may help explain why activation of the anti-inflammatory CB2R leads to inhibition of NLRP3 inflammasome priming and activation in mouse BV2 microglia stimulated with LPS and ATP as well as in a mouse model of EAE. Such CB2R activation reduces the severity of EAE in mice. Thus CB2R agonists similar to the HU-308 used in our work may become an effective therapy for treating NLRP3 inflammasome-related diseases by inducing autophagy."


There is a lot of interrelated function with NLRP3 and various autoimmune and auotinflammatory conditions.


"Nothing happens in a vacuum in life: every action has a series of consequences, and sometimes it takes a long time to fully understand the consequences of our actions."

Khaled Hosseini

The Adaptor MAVS Promotes NLRP3 Mitochondrial Localization and Inflammasome Activation


NLRP3 is involved in inflammatory conditions highlighted in RA studies and effect. The mitochondrial issues in Autism likely relate to this function and immune stimulation due to various causes including vaccines. Still not sure if TNFAIP3 expression in some with inflammatory conditions related to Autism bears on the increase of NF-kappa B found in groups with Autism.

Vaccine Adjuvants - Review Good To Read

Mechanisms of adjuvants

"Adjuvants may exert their effects through different mechanisms. Some adjuvants, such as alum and emulsions (e.g. MF59®), function as delivery systems by generating depots that trap antigens at the injection site, providing slow release in order to continue the stimulation of the immune system. These adjuvants enhance the antigen persistence at the injection site and increase recruitment and activation of antigen presenting cells (APCs). Particulate adjuvants (e.g. alum) have the capability to bind antigens to form multi-molecular aggregates which will encourage uptake by APCs [1].
Some adjuvants are also capable of directing antigen presentation by the major histocompatibility complexes (MHC) [1].
Other adjuvants, essentially ligands for pattern recognition receptors (PRR), act by inducing the innate immunity, predominantly targeting the APCs and consequently influencing the adaptative immune response. Members of nearly all of the PRR families are potential targets for adjuvants. These include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs) and C-type lectin receptors (CLRs). They signal through pathways that involve distinct adaptor molecules leading to the activation of different transcription factors. These transcription factors (NF-κB, IRF3) induce the production of cytokines and chemokines that play a key role in the priming, expansion and polarization of the immune responses. Activation of some members of the NLR family, such as NLRP3 and NLRC4, triggers the formation of a protein complex, called inflammasome, implicated in the induction of the pro-inflammatory cytokines IL-1β [2] and IL-18. The NLRP3 and NLRC4 inflammasomes have been involved in the innate immunity induced by certain adjuvants but their mechanism of action remains unclear.

Alum & emulsions

Alum is the most commonly used adjuvant in human vaccination. It is found in numerous vaccines, including diphtheria-tetanus-pertussis, human papillomavirus and hepatitis vaccines [3]. Alum provokes a strong Th2 response, but is rather ineffective against pathogens that require Th1–cell-mediated immunity. Alum induces the immune response by a depot effect and activation of APCs. Recently, the NLRP3 inflammasome has been linked to the immunostimulatory properties of alum [2] although its role in adjuvant-induced antibody responses remains controversial."


There is a lot unknown about the mitochondrial relation with NLRP3. I theorize a relation between NLRP3, NEk7,and microtubule formation and that this bears on neuronal plasticity and function. I have not gotten very far yet.
TNFAIP3 - Wiki

"This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. Knockout studies of a similar gene in mice suggested that this gene is critical for limiting inflammation by terminating TNF-induced NF-kappa B responses.[2]"




Measurement in saliva from neurotypical adults of biomarkers pertinent to autism spectrum disorders



To be clear, after the pathology in the gut than nutrient and vitamin status would change and supplementation of some vitamins would then become therapeutic.


Definitely two reports, after the Wiki blurb, that are extremely woth reading below. It seems that while an immune stressor or trigger like vaccines may start or elevate a condition, the table has often been set in the womb as autism occurs without vaccine being implicated and maybe more so as the years go by. If autism was exceedingly rare before 194o then it would appear that a lack of vitamin supplementation was not a reason for autism. It may be that the increase in processed foods had a bearing on a mother and, by extension, child's neurodevelopment, but the total picture does not lend credence to the idea that lack of vitamin's was a big factor in the increase in autism. The increased ingestion of some vitamins along with all the environmental factors{negative contributors, toxins, chemicals, metals, v etc...} could have made the need for other vitamins greater and a cycle of supplementation of some vitamins at certain states, esp. in pregnancy became more crucial. For example the rise of spina bifida causing more folic acid to curb. Anyway, the altered gene expression in those with autism and other conditions may be a reaction to the taxing of some nutrients and the excess of others. Morning sickness may be in part result of these imbalances and for the disturbance in the methyl groups sulfation and other systems needed catecholamine cycles and processing xenobiotics and detoxification. It may be why only certain vitamins are found helpful for some autism as well as the imbalance creates greater need.

Wiki - Vitamin

"Until the mid-1930s, when the first commercial yeast-extract vitamin B complex and semi-synthetic vitamin C supplement tablets were sold, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) usually greatly altered the types and amounts of vitamins ingested. However, vitamins have been produced as commodity chemicals and made widely available as inexpensive semisynthetic and synthetic-source multivitamin dietary and food supplements and additives, since the middle of the 20th century."


Microarray Analysis Reveals Higher Gestational Folic Acid Alters Expression of Genes in the Cerebellum of Mice Offspring—A Pilot Study


"Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA) in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development."


Early Infant Exposure to Excess Multivitamin: A Risk Factor for Autism?


"Autism, a neurodevelopmental disorder that affects boys more than girls, is often associated with altered levels of monoamines (serotonin and catecholamines), especially elevated serotonin levels. The monoamines act as both neurotransmitters and signaling molecules in the gastrointestinal and immune systems. The evidence related to monoamine metabolism may be summarized as follows: (i) monoamine neurotransmitters are enzymatically degraded/inactivated by three mechanisms: oxidative deamination, methylation, and sulfation. The latter two are limited by the supply of methyl groups and sulfate, respectively. (ii) A decrease in methylation- and sulfation-mediated monoamine inactivation can be compensated by an increase in the oxidative deamination catalyzed by monoamine oxidase, an X-linked enzyme exhibiting higher activity in females than in males. (iii) Vitamins can, on one hand, facilitate the synthesis of monoamine neurotransmitters and, on the other hand, inhibit their inactivation by competing for methylation and sulfation. Therefore, we postulate that excess multivitamin feeding in early infancy, which has become very popular over the past few decades, may be a potential risk factor for disturbed monoamine metabolism. In this paper, we will focus on the relationship between excess multivitamin exposure and the inactivation/degradation of monoamine neurotransmitters and its possible role in the development of autism...."

"It has been known for over a century that the dose-response curve for many micronutrients is nonmonotonic, having an initial stage of increasing benefits with increased intake, followed by increasing costs as excesses become toxic [39]. Both vitamin deficiency and vitamin excess are known to cause toxicity, including neurotoxicity [15, 40]. A meta-analysis of randomized trials of antioxidant supplements for primary and secondary prevention suggests that supplementation of vitamin A and E may increase mortality [41]. Supplemental folic acid (the synthetic form of folate) was also found to be associated with increased mortality [42, 43]. Davis and colleagues [44] found an association between high serum thiamine levels and sudden infant death syndrome (SIDS, a sudden and unexplained infant death most likely to occur between 2 and 4 months of age), and they further demonstrated that high doses of thiamine could cause death in rabbits and mice due to respiratory failure."



Speaking of Dr. Wakefield, he, with others released a report a number of years back about theses matters related to the second article in last post. It is linked below. The report mentions esophageal reflux, gastritis, and constipation related to autism and the gut matters discussed. I had noted and dealt with these in my wife in 96' forward and found it very confirming that these conditions{with others} originally present in that overall assessment were later associated as conditions found in much higher amounts in many with autism.

Review article: The concept of enterocolonic encephalopathy, autism and opioid recepter ligands


In some, maybe a large part, the vaccines may disturb the gut, and brain neuroplasticity along with the glial effects. Then the gut function being altered makes this an ongoing pathology with neuroinflammation and mild or more encephalopathy.

Perinatal brain damage in children: neuroplasticity, early intervention, and molecular mechanisms of recovery.


"During the perinatal period, the nervous system is very vulnerable to insult. At this time, the brain undergoes fast and complex maturational processes such as synaptogenesis, arborization, and apoptosis, and the response to the insult is highly dependent on its exact timing. There is evidence that some of the neuroplastic mechanisms adopted by the young brain after damage are unavailable at a later stage of maturation. This applies, for example, to the reorganization of language, the sensorimotor system, or the visual system. Expanding our knowledge on these mechanisms could help the development of early therapeutic interventions aimed at supporting and enhancing functional reorganization at a time of greatest potential brain plasticity."



The elements of immune response to HBV and related synaptic plasticity mentioned in the last post overlaps with those elements of inflammatory microglial activation associated with intestinal and peripheral inflammation. The nest report details a number related things such as colitis that covers and may include the similar gut issue defined by Dr. Wakefield. The whole article should be read to see the full idea. It also makes a reassessment of minocycline in some with autism seem desirable.

Microglia-Dependent Alteration of Glutamatergic Synaptic Transmission and Plasticity in the Hippocampus during Peripheral Inflammation


"Peripheral inflammatory diseases are often associated with behavioral comorbidities including anxiety, depression, and cognitive dysfunction, but the mechanism for these is not well understood. Changes in the neuronal and synaptic functions associated with neuroinflammation may underlie these behavioral abnormalities. We have used a model of colonic inflammation induced by 2,4,6-trinitrobenzenesulfonic acid in Sprague Dawley rats to identify inflammation-induced changes in hippocampal synaptic transmission. Hippocampal slices obtained 4 d after the induction of inflammation revealed enhanced Schaffer collateral-induced excitatory field potentials in CA1 stratum radiatum. This was associated with larger-amplitude mEPSCs, but unchanged mEPSC frequencies and paired-pulse ratios, suggesting altered postsynaptic effects. Both AMPA- and NMDA-mediated synaptic currents were enhanced, and analysis of AMPA-mediated currents revealed increased contributions of GluR2-lacking receptors. In keeping with this, both transcripts and protein levels of the GluR2 subunit were reduced in hippocampus. Both long-term potentiation (LTP) and depression (LTD) were significantly reduced in hippocampal slices taken from inflamed animals. Chronic administration of the microglial/macrophage activation inhibitor minocycline to the inflamed animals both lowered the level of the cytokine tumor necrosis factor α in the hippocampus and completely abolished the effect of peripheral inflammation on the field potentials and synaptic plasticity (LTP and LTD). Our results reveal profound synaptic changes caused by a mirror microglia-mediated inflammatory response in hippocampus during peripheral organ inflammation. These synaptic changes may underlie the behavioral comorbidities seen in patients.


Peripheral inflammation is a feature of many diseases, including inflammatory bowel disease (Häuser et al., 2011), rheumatoid arthritis (Maini et al., 2004; Mayoux-Benhamou, 2006), and inflammatory liver disease (Gralnek et al., 2000; Butterworth, 2013; D'Mello and Swain, 2014), and is often associated with marked behavioral changes, including mood disorders, fatigue, cognitive and memory dysfunction, and sleep disturbances. Moreover, the inflammation is capable of aggravating other neurological and neuropsychiatric conditions, including seizure disorders (Vezzani et al., 2013), major depression (Raison et al., 2006), Alzheimer's disease (Ferrari and Tarelli, 2011), multiple sclerosis (Benson and Kerr, 2014), Parkinson's disease (Collins et al., 2012), and stroke (Ferrari and Tarelli, 2011). These comorbid effects can have considerable impact on both health and the quality of life of the patients.

The behavioral manifestations associated with peripheral inflammation clearly indicate CNS involvement; thus, a number of mechanisms have been suggested to underlie the communication between these peripheral inflammatory conditions and the brain (Walker et al., 2014). Peripheral tissue inflammation results in the production of proinflammatory cytokines that signal to the brain via cytokine receptors at the blood–brain barrier, within circumventricular organs or on sensory afferents. There is now compelling evidence that the cytokines generated during peripheral inflammation activate a secondary, mirror inflammatory response in the brain that is characterized by activation of microglia and production of proinflammatory cytokines, most importantly, tumor necrosis factor α (TNFα), interleukin (IL)-1β, and IL-6 (Quan et al., 1998; D'Mello et al., 2013; Thomson et al., 2014). These cytokines have profound effects on synaptic transmission and synaptic plasticity (for review, see Pickering and O'Connor, 2007), effects that most likely underlie the cognitive dysfunction, altered behavior, and other interactions with preexisting pathologies seen in peripheral inflammatory disease (Raison et al., 2006; Galic et al., 2012; Santello and Volterra, 2012; Nisticò et al., 2013; Camara et al., 2015). There is accumulating evidence that alterations in glutamatergic transmission underlie some of these behaviors (for review, see Walker et al., 2014).

In a rat model of inflammatory colitis, we previously reported reduced thresholds to chemically induced seizures in vivo and increased excitability of the hippocampus in vitro (Riazi et al., 2008). The increased excitability is mediated by activated microglia and production of TNFα in the hippocampus. However, the neuronal and synaptic changes that correlate with such increased excitability are unknown. Previous work indicates that TNFα alters expression of glutamate (Stellwagen and Malenka, 2006) and GABA (Pribiag and Stellwagen, 2013) receptors in vitro. In addition, direct application of proinflammatory cytokines to hippocampal slices in vitro alters the ability of excitatory synapses to display long-term potentiation (LTP; Pickering and O'Connor, 2007), a type of plasticity associated with learning and memory. Following up on our previous studies revealing an elevation of inflammatory cytokines in the brain (Riazi et al., 2008), we hypothesize that glutamatergic synaptic transmission and plasticity are altered during inflammatory colitis due to microglial activation. In a rat model of inflammatory colitis, we now report changes in hippocampal synaptic transmission associated with a profound reduction in synaptic plasticity."


Autistic enterocolitis: Fact or fiction?


"Autism spectrum disorder refers to syndromes of varying severity, typified by impaired social interactions, communicative delays and restricted, repetitive behaviours and interests. The prevalence of autism spectrum disorders has been on the rise, while the etiology remains unclear and most likely multifactorial. There have been several reports of a link between autism and chronic gastrointestinal symptoms. Endoscopy trials have demonstrated a higher prevalence of nonspecific colitis, lymphoid hyperplasia and focally enhanced gastritis compared with controls. Postulated mechanisms include aberrant immune responses to some dietary proteins, abnormal intestinal permeability and unfavourable gut microflora. Two autism spectrum disorder patients with chronic intestinal symptoms and abnormal endoscopic findings are described, followed by a review of this controversial topic."...

There have been several reports, mainly anecdotal, of a link between ASD and chronic gastrointestinal (GI) symptoms; however, scientific data are scarce and often criticized. Frequent complaints have included chronic diarrhea, bloating, abdominal pain, distension and abnormal stool consistency. In a recent cross-sectional study, comparing autistic children with matched neurotypical controls as well as children with other developmental disabilities (ODD), 70% of children with ASD reported a history of GI complaints, compared with 28% of neurotypical controls (P<0.001) and 42% with ODD (P=0.03) (5). GI problems have more commonly been linked to a ‘regressive’ form of autism, characterized by loss of previously acquired skills and late onset of behavioural anomalies, not observed in the first year of life.

One of the earliest studies investigating GI anomalies in autistic children was reported by Wakefield et al (6) in 1998. In this study, 12 children with regressive developmental disorders (nine of whom were autistic) were all reported to have abnormal colonoscopies. The most consistent finding was lymphoid nodular hyperplasia (LNH), present in nine of the 12 children. Eight had mucosal abnormalities including granularity, loss of vascular pattern, patchy erythema, aphthoid ulcerations and ‘red halo’ signs in the cecal base. Histologically, the lamina propria was infiltrated by mononuclear cells in a focal or diffuse pattern, in the absence of intraepithelial lymphocytes, granulomata or crypt abscesses (6). This mild to moderate colitis was deemed nonspecific on the basis of not fulfilling criteria for either Crohn’s disease or ulcerative colitis.

Criticism regarding the ‘normalcy’ of LNH in children prompted Wakefield et al (7) to perform ileocolonoscopy in 60 children with regressive developmental disorders and compare them with 37 developmentally normal controls. In this trial, ileal LNH was present in 93% of affected children versus 14.3% of controls (P<0.001), with chronic colitis in 88% of affected children versus 4.5% of controls (7).

With respect to the upper GI tract, Horvath et al (8) investigated 36 autistic children complaining of abdominal pain, bloating or chronic diarrhea by gastroscopy. The most common histological finding was reflux esophagitis (69.4%), while 41.7% had chronic gastritis and 66.7% had chronic duodenitis in the absence of H pylori infection...."

ASD patients and their caregivers often report improvement on elimination diets, not only in the GI symptoms, but also in behavioural and cognitive problems such as hyper-activity, communication skills and attentiveness. Interestingly, 36% of children with ASD have a history of cow’s milk and/or soy protein intolerance in infancy (8). Also, while studies have not proven an increased incidence of celiac disease in these individuals, parents have often reported an improvement in their child’s behavioural disturbances on a gluten-free diet. These benefits have not consistently been seen in randomized trials (10), however a Cochrane review (11) did report a significant reduction in autistic traits on a gluten-free casein-free diet.

One hypothesis is that ASD may be accompanied by aberrant innate immune responses to dietary proteins, leading to GI inflammation and aggravation of behavioural problems. One study (12) measuring proinflammatory cytokines in response to common dietary proteins showed a greater than two SD excess in tumour necrosis factor-alpha and interferon-gamma production in response to gluten and cow’s milk protein among ASD children compared with controls. A subsequent study confirmed a higher prevalence of elevated tumour necrosis factor-alpha and interleukin-12 production with beta-lactoglobin and alpha-lactoglobin, but not casein, in autistic children as well as children with nonallergic food hypersensitivity, compared with normal controls (13).

Another theory suggests that abnormal intestinal permeability in children with ASD causes them to absorb fragments of incompletely broken-down peptides such as gluten or casein, which cross the blood-brain barrier and act as endogenous opioids. D’Eufemia et al (14) demonstrated a higher mean lactulose recovery in 43% of autistic subjects versus none of the controls.

The gut microflora has also been targeted as a potential player. There have been anecdotal reports of the onset of autism following broad-spectrum antibiotics, suggesting that disruption of the indigenous flora may lead to colonization by neurotoxin-producing bacteria. Autistic children have been shown to have higher counts and more species of clostridia than age- and sex-matched controls (15–17). A small prospective trial (18) demonstrated a significant but transient improvement in autistic features following a course of vancomycin therapy, with relapses presumed to occur because of persistent spores that proliferate on antibiotic discontinuation."



The last two posts were quite speculative, but even so I mentioned possible effects of neurogenesis in the pre-frontal cortex and apparently those neurons numbers are static at birth except in those born pre-mature so a vaccine would seem not to be causing neurogenesis there. The reports are speaking of neurogenesis in the hippocampus though synaptic effects might be more broad.


This report by the same authors answers whether there could be conflicting effects from other vaccines. I should have read a bit further in the kinks on the original page. They say Hepatitis B vaccine gives an opposite effect.

Neonatal vaccination with bacillus Calmette-Guérin and hepatitis B vaccines modulates hippocampal synaptic plasticity in rats.


"Immune activation can exert multiple effects on synaptic transmission. Our study demonstrates the influence of neonatal vaccination on hippocampal synaptic plasticity in rats under normal physiological conditions. The results revealed that neonatal BCG vaccination enhanced synaptic plasticity. In contrast, HBV hampered it. Furthermore, we found that the cytokine balance shifted in favour of the T helper type 1/T helper type 2 immune response in BCG/HBV-vaccinated rats in the periphery. The peripheral IFN-γ:IL-4 ratio was positively correlated with BDNF and IGF-1 in the hippocampus. BCG raised IFN-γ, IL-4, BDNF and IGF-1 and reduced IL-1β, IL-6, and TNF-α in the hippocampus, whereas, HBV triggered the opposite effects."



I put the wrong title for the abstract in the last post it is:
Neonatal BCG Vaccination of Mice Improves Neurogenesis and Behavior in Early Life.



This is more of an anecdotal report, but it is funny how they so easily tie the BCG vaccine to neurogenesis and report what appears to be a positive effect inducing ostensibly neuroprotection in mice. For kicks, and giving the theory and results some credence, think of the notion of the proposition that a somewhat common vaccine can effect the brain. Also, if this one does would other vaccines quite possibly, or even likely have effects in the brain as well? If this theory is translated to humans then tampering with microglial activation in an infant who does not need intervention for brain conditions is rolling the dice and you have to ask what is the unintended consequence of increasing neurogenesis in subject. Given that many with autism have increased neuronal synapses and an excess of neurons in the pre-frontal cortex it makes you wonder in vaccines are triggering these outcomes. Not to mention possible compound effects from multiple vaccines and/or conflicting effects on microglia from various vaccines.
The opening line of the abstract says;
"Bacillus Calmette-Guérin (BCG) is administered to neonates worldwide, but it is still unknown whether this neonatal vaccination affects brain development during early postnatal life, despite the close association of the immune system with the brain."

This implies that it is reasonable to wonder what immune system stimulation/alteration might do in the brain and I would add the gut and maybe additional organs.

Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.


"Bacillus Calmette-Guérin (BCG) is administered to neonates worldwide, but it is still unknown whether this neonatal vaccination affects brain development during early postnatal life, despite the close association of the immune system with the brain. Newborn C57BL/6 mice were injected subcutaneously with BCG or phosphate-buffered saline (PBS) and their mood status and spatial cognition were observed at four and eight weeks (w) old. The mice were also subjected to tests at 2 and 6 w to examine BCG's effects on neurogenesis, the hippocampal microglia phenotype and number, and the expression of hippocampal neuroimmune molecules and peripheral cytokines. The BCG-injected mice showed better behavioral performances at 4 w. We observed elevated neurogenesis, M2 microglial activation and a neurotrophic profile of neuroimmune molecules [more interferon (IFN)-γ, interleukin (IL)-4, transforming growth factor (TGF)-β, brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF)-1 and less tumor necrosis factor (TNF)-α and IL-1β] in the hippocampus of the 2-w-old BCG-mice. In the periphery, BCG induced a T helper (Th)-1 serum response. At the individual level, there were positive correlations between the serum IFN-γ/IL-4 ratio and the levels of neurotrophins and neurogenesis in the hippocampus. These findings suggest that neonatal BCG vaccination improved neurogenesis and mouse behavior in early life by affecting the neuroimmune milieu in the brain, which may be associated with a systemic Th1 bias."


The development of brain trajectory in autism suggests the growth and microglial status is later skewed negatively and boosting or skewing in infancy would be a good idea to consider for later maladaptive function.


More inflammation, yet this report suggests less able to fight off infection in autism.

Study confirms mitochondrial deficits in children with autism

"Children with autism experience deficits in a type of immune cell that protects the body from infection. Called granulocytes, the cells exhibit one-third the capacity to fight infection and protect the body from invasion compared with the same cells in children who are developing normally.

The cells, which circulate in the bloodstream, are less able to deliver crucial infection-fighting oxidative responses to combat invading pathogens because of dysfunction in their tiny energy-generating organelles, the mitochondria....

In an earlier study the research team found decreased mitochondrial fortitude in another type of immune cell, the lymphocytes. Together, the findings suggest that deficiencies in the cells’ ability to fuel brain neurons might lead to some of the cognitive impairments associated with autism. Higher levels of free radicals also might contribute to autism severity.

“The response found among granulocytes mirrors earlier results obtained with lymphocytes from children with severe autism, underscoring the cross-talk between energy metabolism and response to oxidative damage,” said Cecilia Giulivi, professor in the Department of Molecular Biosciences in the UC Davis School of Veterinary Medicine and the study’s senior author.

“It also suggests that the immune response seems to be modulated by a nuclear factor named NRF2,” that controls antioxidant response to environmental factors and may hold clues to the gene-environment interaction in autism, Giulivi said."



Increased plasma levels of the high mobility group box 1 protein (HMGB1) are associated with a higher score of gastrointestinal dysfunction in individuals with autism.


"Autism is a disorder of neural development characterized by impairments in communication, social interaction, restricted interests and repetitive behavior. The etiology of autism is poorly understood, the evidence indicates that inflammation may play a key role. In autism a high prevalence of gastrointestinal disturbances is reported, that are linked to a low-grade chronic inflammation of the intestinal mucosa. High mobility group box 1 protein (HMGB1) is an intranuclear protein that can be passively released from necrotic cells or actively secreted under inflammatory conditions as alarmin or late proinflammatory cytokine. The objective of this study was to measure plasma levels of HMGB1 in individuals with autism and to analyze their association with gastrointestinal symptoms. The study involved 31 subjects with low-functioning autistic disorder aged 2-22 years and 16 healthy controls. Plasma HMGB1 levels were significantly higher in individuals with autism than in controls (13.8+/-11.7 ng/ml vs. 7.90+/-4.0 ng/ml, p<0.02). In subjects with plasma HMGB1 levels higher than 11 ng/ml severe forms of GI disorders were more prevalent (83.3 %) than in subjects with lower levels (38.9 %, p<0.04). Results of the study support the involvement of the systemic low-grade inflammation in the pathomechanisms of autism and its possible association with GI symptoms."


Increased serum levels of high mobility group box 1 protein in patients with autistic disorder.


"High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein that functions as an activator for inducing the immune response and can be released from neurons after glutamate excitotoxicity. The objective of the present study was to measure serum levels of HMGB1 in patients with autistic disorder and to study their relationship with clinical characteristics.

We enrolled 22 adult patients with autistic disorder (mean age: 28.1+/-7.7 years) and 28 age- and gender-matched healthy controls (mean age: 28.7+/-8.1 years). Serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay (ELISA).

Compared with healthy subjects, serum levels of HMGB1 were significantly higher in patients with autistic disorder (10.8+/-2.6 ng/mL versus 5.6+/-2.5 ng/mL, respectively, P<0.001). After adjustment for potential confounders, serum HMGB1 levels were independently associated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction.

These results suggest that HMGB1 levels may be affected in autistic disorder. Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder."



Thanks, Visitor


Serotonin, tryptophan metabolism and the brain-gut-microbiome axis

"Tryptophan and its metabolite serotonin have an expansive physiological repertoire, making them fundamental to health and there are numerous associations between alterations in this system and disease [1], [2] and [3]. A growing body of data is also pointing to the influence of this system far beyond the traditional focus on its signalling pathways in the central nervous system (CNS) (see Reviews in this Special Issue). Moreover, emerging data implicates the gut microbiome in the regulation of brain and behaviour in general with a specific emphasis on its impact on tryptophan metabolism and the serotonergic system.

Research in this area builds on the principles of the brain-gut axis concept (see Fig. 1), a bidirectional communication network between the brain and the gut with serotonin functioning as a key signalling molecule in both the enteric nervous system (ENS) and the CNS [4], [5] and [6]. Recently, it has become clear that the gut microbiome is a critical component of this axis and one which exerts control at multiple levels, not just locally in the gastrointestinal tract [7], [8], [9] and [10]. Using a variety of preclinical strategies, it has been established that manipulating the composition of the gut microbiota across the lifespan or altering the trajectory of microbial colonisation of the gastrointestinal tract early in life influences the availability of tryptophan. In tandem and possibly related to this capacity, this research has also illuminated a role for the gut microbiota in serotonergic signalling at the level of the CNS. There is also a substantial overlap between many of the behaviours underpinned by serotonergic signalling and those which are influenced by alterations in the composition, diversity or stability of the microbiota. Taken together, it seems plausible that the gut microbiota can either directly or indirectly recruit tryptophan metabolism and serotonergic signalling within the framework of the brain-gut axis to modulate host behaviour."


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