tag:blogger.com,1999:blog-1892134081049774386.post3243175175266744495..comments2023-12-02T09:37:08.472-05:00Comments on Autism Jabberwocky: Ancestry of Pink Disease and AutismM.J.http://www.blogger.com/profile/12033918835169823548noreply@blogger.comBlogger6125tag:blogger.com,1999:blog-1892134081049774386.post-79280460490955701112011-08-12T00:42:40.474-04:002011-08-12T00:42:40.474-04:00We have to analyze calomel exposure or other simil...We have to analyze calomel exposure or other similar compound by ingestion at an age when teeth are present ( near 6 months when calomel was used), with previous medical history in grandparents in terms of biochemical, BBB and immune status and gut flora status vs thimerosal exposure by injection - with coexposure with Alum and other compounds – in accumulative way since birth for an important part of the grandchildren (since the year of the hepatitis B vaccine introduction in USA) and taking into account prenatal exposure in grandchildren.Therefore <br />a) the path of the exposure is different (ingestion vs injection) <br />b) the chemical related to the exposure is different ( calomel vs thimerosal) and therefore metabolism in susceptible people is not (necessarily) similar. <br />c) the presentation of the impact is different (acrodynia vs potential contribution from an encephalopatic state related to ASD to tics- a finding recently reported in thimerosal analysis impact) <br />d) the metabolic management is individualized and different in susceptible people .(ingestion - through the gut and with the modifications related to the status of the gut flora vs injected without contact with gut flora and modifications related to). It is known from long time ago that gut flora modulates mercury speciation and methylation. It is also known that antibiotics pretreatment increases the accumulation from studies in rats. <br />e) the exposure to Hg compound is concomitant to other coexposures and affected by previous xenobiotics (for example antibiotics or tylenol) at a completely different developmental window- powder teeth were used when children have teeth , even when they could be used daily. Even more, the previous history at 6 months of age- when in general calomel was used – is completely different in grandchildren vs grandparents in terms of pediatric management of childhood (and therefore predisposition to adverse effects of low doses of Hg).María Lujánhttps://www.blogger.com/profile/05619003228550909446noreply@blogger.comtag:blogger.com,1999:blog-1892134081049774386.post-64613112599665623552011-08-12T00:41:27.013-04:002011-08-12T00:41:27.013-04:00The analysis should be done IMO considering the pe...The analysis should be done IMO considering the pediatric management of the childhood for the grandparents, from food to other medications used before the pink disease in grandparents appeared. Remember the cod liver oil for example, given to children decades ago to avoid ricketts? At the best of my knowledge breast feeding was a rule- sometimes for years- and even when there were other problems, food had a much higher quality in terms of nutrients for mothers- generally at home. Mothers were not vaccinated with tetanus/flu for example or Rh shots. <br /><br />The primary mistake is to assume that thimerosal or Hg is an only cause, without the consideration of the accumulative/additional impact of environment. Without careful analysis of the medical prenatal and postnatal history and xenobiotics (tylenol use for fever for example) /infections/gut flora status/vaccines/others in grandparents, children- and grandchildren the exposure can not be properly analyzed in context, Without the consideration of other factors such as glutathione status in the context of the work of James et al. the questions are ill conceived. <br /><br />For the critics is a matter of the same path of potential damage in susceptible people from pink disease and in ASD. BUT to do so it has to equate two completely different exposures in terms of mechanism of action- with differences only in the supposed dose. The question is centered on the doses in absence of anything elseMaría Lujánhttps://www.blogger.com/profile/05619003228550909446noreply@blogger.comtag:blogger.com,1999:blog-1892134081049774386.post-44352370442649661712011-08-12T00:38:38.262-04:002011-08-12T00:38:38.262-04:00Now, there are several published manuscripts on bi...Now, there are several published manuscripts on biochemical and metabolic problems with management of xenobiotics found in autistic children.<br />One of them<br />Biol Trace Elem Res. 2011 Jul 14. [Epub ahead of print] <br />Altered Heavy Metals and Transketolase Found in Autistic Spectrum Disorder. <br />Obrenovich ME, Shamberger RJ, Lonsdale D. <br />Autism and autism spectrum disorder (ASD) are developmental brain disorders with complex, obscure, and multifactorial etiology. Our recent clinical survey of patient records from ASD children under the age of 6 years and their age-matched controls revealed evidence of abnormal markers of thiol metabolism, as well as a significant alteration in deposition of several heavy metal species, particularly arsenic, mercury, copper, and iron in hair samples between the groups. Altered thiol metabolism from heavy metal toxicity may be responsible for the biochemical alterations in transketolase, and are mechanisms for oxidative stress production, dysautonomia, and abnormal thiamine homeostasis. It is unknown why the particular metals accumulate, but we suspect that children with ASD may have particular trouble excreting thiol-toxic heavy metal species, many of which exist as divalent cations. Accumulation or altered mercury clearance, as well as concomitant oxidative stress, arising from redox-active metal and arsenic toxicity, offers an intriguing component or possible mechanism for oxidative stress-approaches and avenues of exploration for this devastating and growing disease.<br /><br />Mutat Res. 2010 Oct;705(2):130-40. <br />The relevance of the individual genetic background for the toxicokinetics of two significant neurodevelopmental toxicants: mercury and lead. <br />Gundacker C, Gencik M, Hengstschläger M. <br />The heavy metals mercury and lead are well-known and significant developmental neurotoxicants. This review summarizes the genetic factors that modify their toxicokinetics. Understanding toxicokinetics (uptake, biotransformation, distribution, and elimination processes) is a key precondition to understanding the individual health risks associated with exposure. We selected candidate susceptibility genes when evidence was available for (1) genes/proteins playing a significant role in mercury and lead toxicokinetics, (2) gene expression/protein activity being induced by these metalsand (3) mercury and lead toxicokinetics being affected by gene knockout/knockdown or (4) by functional gene polymorphisms. The genetic background is far better known for mercury than for lead toxicokinetics. Involved are genes encoding L-type amino acid transporters, organic anion transporters, glutathione (GSH)-related enzymes, metallothioneins, and transporters of the ABC family. Certain gene variants can influence mercury toxicokinetics, potentially explaining part of the variable susceptibility to mercury toxicity. Delta-aminolevulinic acid dehydratase (ALAD), vitamin D receptor (VDR) and hemochromatosis (HFE) gene variants are the only well-established susceptibility markers of lead toxicity in humans. Many gaps remain in our knowledge about the functional genomics of this issue. This calls for studies to detect functional gene polymorphisms related to mercury- and lead-associated disease phenotypes, to demonstrate the impact of functional polymorphisms and gene knockout/knockdown in relation to toxicity, to confirm the in vivo relevance of genetic variation, and to examine gene-gene interactions on the respective toxicokinetics. Another crucial aspect is knowledge on the maternal-fetal genetic background, which modulates fetal exposure to these neurotoxicants. To completely define the genetically susceptible risk groups, research is also needed on the genes/proteins involved in the toxicodynamics, i.e., in the mechanisms causing adverse effects in the brain. Studies relating the toxicogenetics to neurodevelopmental disorders are lacking (mercury) or very scarce (lead). Thus, the extent of variability in susceptibility to heavy metal-associated neurological outcomes is poorly characterized.María Lujánhttps://www.blogger.com/profile/05619003228550909446noreply@blogger.comtag:blogger.com,1999:blog-1892134081049774386.post-67442785966643410202011-08-11T18:12:29.581-04:002011-08-11T18:12:29.581-04:00If the researchers could tie these numbers back to...If the researchers could tie these numbers back to an actual genetic/environmental risk factor or if they replicated the study in another population using more rigorous methods then that would definitively give their findings more weight.<br /><br />If there is something to these findings, I have to wonder whether it would be a susceptibility to Hg or genetic/epigenetic damage caused by pink disease (or both) that makes the difference.M.J.https://www.blogger.com/profile/12033918835169823548noreply@blogger.comtag:blogger.com,1999:blog-1892134081049774386.post-38664413071793986492011-08-11T11:31:18.298-04:002011-08-11T11:31:18.298-04:00Hi MJ
The point is that I , at least, disagree wit...Hi MJ<br />The point is that I , at least, disagree with any kind of extreme position. I do think that the finding may be a begining of a deep study about predisposition and impact of nature of exposure, and the correlation is important; BUT CLINICAL studies are needed IMO- and also different genetic ones.<br />I disagree with the kind of questions done by the critics and with a correlation extrapolated to causation with this kind of data, but the work is not meaningless in an objetive context.<br />If you want, I may elaborate more.María Lujánhttps://www.blogger.com/profile/05619003228550909446noreply@blogger.comtag:blogger.com,1999:blog-1892134081049774386.post-63197923283970995612011-08-10T14:55:29.101-04:002011-08-10T14:55:29.101-04:00Thanks for the overview of this study. I have not ...Thanks for the overview of this study. I have not seen the full-text of the paper yet but have read the press release from Swinburn University which states the authors intentions of this study showing that genes and environment might share centre-stage, at least in their described cohort. I like the fact that they are continuing this work to look at the "cellular and genetic characteristics" which should definitely be worth a look when it eventually arrives on the research scene.<br />http://www.swinburne.edu.au/chancellery/mediacentre/media-centre/news/2011/08/australian-research-finds-autism-risk-Paul Whiteleyhttps://www.blogger.com/profile/14288851488012254897noreply@blogger.com