Impaired Detoxifications Systems
How might issues of impaired detoxification affect my child?
Associated Signs & Symptoms* often reported by Parents & Carers:-
* This list is not exhaustive, one or more signs may indicate a potential problem with detoxification
The Issues Identified
Science, Studies, Papers & Presentations
Thimerosal Neurotoxcity is Associated with Glutathione Depletion
Weak Phase 11 Dextoification
Peroximal Malfunction
Metallothionein (MT) Dysfunction in Autism
Higher Blood Lead Levels
Higher Mercury Burden than Controls
Low Hair Mercury in First Baby Hair Cuts in Chidlren with Autism
Low Glutathione Synsthesis
Deficits in Methylation Cycle
Evidence of Harm? (Video)
The Autism-Vaccine Connection (Video)
Autism, the Misdiagnosis of our Future Generations
Testimony, U.S. Congressional Sub-Committee Hearing
Rashid A. Buttar, DO, Vice Chairman, American Board of Clinical Metal Toxicology
May 6, 2004
From Epidemiology, Clinical Medicine, Molecular Biology, and Atoms, to Politics: A Review of the Relationship Between Thimerosal and Autism
Submitted to the Institute of Medicine, of the US National Academy of Sciences
Dr. Mark R. Geier, David A. Geier
January 2004
This comprehensive report, authored by a noted geneticist and his son, summarizes a wide body of current scientific research detailing the link between Thimerosal and neurodevelopmental disorders including autism. Among other evidence, the Geiers, themselves, analyzed vaccine data from three separate sources: the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (both maintained by the Centers for Disease Control and Prevention), and the US Department of Education. In each of these separate analyses, the Geiers found a strong correlation between Thimerosal-containing vaccines and autism. Excerpt:
"We determined that there was a 6-fold statistically significantly (p<0.05) increased incidence rate of autism reported to VAERS following thimerosal-containing DtaP vaccines in comparison to thimerosal-free DtaP vaccines." [In other words, the risk that a child would develop autism was 600% more likely after receiving a DtaP vaccine containing Thimerosal than one without.]
[In the Vaccine Safety Datalink, the correlation was even stronger:] "We found in our cohort receiving a minimum of three doses of thimerosal-containing DtaP vaccine in comparison to our cohort receiving a minimum of three doses of themirosal-free DtaP vaccine only, that there was statistically significantly increased risk for autism (relative risk = 27.6...) [In this case, in other words, the risk that a child would develop autism was 2760% more likely after receiving three DtaP vaccines containing Thimerosal than three without.]
"The evidence presented in this review represents a mere fraction of the many thousands of peer-reviewed articles that have been published by authors from many fields of science and medicine over many decades warning of the dangers of thimerosal. It is clear that the vast evidence in the peer-reviewed literature points to the conclusion that thimerosal has a causal relationship with autism. Regardless of the findings of the Institute of Medicine regarding the relationship between thimerosal and autism, it is clear that thimerosal has no place in medicine. It is also clear, despite claims to the contrary from the American Academy of Pediatrics, the US Public Health Service, FDA, and Institute of Medicine, that thimerosal is still present in a number of vaccines at significant concentrations. Thimerosal should be banned for use in humans at any concentrations.
In conclusion, those who have a decreased ability to excrete mercury, as has been demonstrated for several different genotypes, there can be little doubt that mercury concentrations once administered to children as part of the childhood routine vaccination program schedule resulted in a significant number of children developing autism. This is especially true following a sudden increase in the amount of mercury administered, as occurred in the United States in the early 1990s when the amount of mercury administered to children in the first six months of life more than doubled as part of the routine childhood immunization schedule. It should be kept in mind that the gene pool contains many susceptible individuals who would have been normal but for the mercury in their vaccines.
It is also clear that if somehow, despite the overwhelming evidence, the IOM determines, that either thimerosal did not cause or that they are not sure that it caused the current epidemic of autism and other neurological disorders, that the IOM must demand the immediate expenditure of billions of dollars as part of an all out effort to immediately determine what is causing this epidemic before it totally destroys our society."
Boyd Haley, Ph.D. Reduced Levels of Mercury in First Baby Haircuts of Autistic Children. IOM presentation, Feb 9 2004.
Slides: http://www.iom.edu/view.asp?id=18394
Audio: http://www.iom.edu/view.asp?id=191288
Pastore A et al. Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta. 2003 Jul 1;333(1):19-39. PMID: 12809732
BACKGROUND: Glutathione is a ubiquitous thiol-containing tripeptide, which plays a central role in cell biology. It is implicated in the cellular defence against xenobiotics and naturally occurring deleterious compounds, such as free radicals and hydroperoxides? Glutathione is a critical factor in protecting organisms against toxicity and disease. This review may turn useful for analysing the glutathione homeostasis, whose impairment represents an indicator of tissue oxidative status in human subjects
The Vaccine-Autism Connection - Part I (Thimerosal)
Read and download an Adobe Acrobat (pdf) file
BERNARD RIMLAND, Ph.D., Director Autism Research Institute
April, 2004
Partial list of studies linking thimerosal to Autism
The Centers for Disease Control and the American Academy of Pediatrics have issued a statement asserting that ?the available scientific evidence has not shown thimerosal-containing vaccines to be harmful.? Their statement is false. Following are some of the scientific studies that demonstrate thimerosal, a mercury-containing substance that is used as a preservative, to be harmful and to be a highly probably causal factor in autism. Note that these studies are consistently ignored in the medical establishment?s publications claiming that there is no evidence for vaccine-caused autism.
Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel form of mercury poisoning. Med. Hypotheses. 2001 Apr;56(4):462-71. PMID: 11339848
Geier DA, Geier MR. An assessment of the impact of thimerosal on childhood neurodevelopmental disorders. Pediatr Rehabil. 2003 Apr-Jun;6(2):97-102. PMID: 14534046
Geier MR, Geier DA. Neurodevelopmental disorders after thimerosal-containing vaccines: a brief communication. Exp Biol Med (Maywood). 2003 Jun;228(6):660-4. PMID: 12773696
Geier & Geier. Parents' worries about thimerosal in vaccines are well founded!
http://pediatrics.aappublications.org/cgi/eletters/112/6/1394
David Baskin, M.D. et al. Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts. Toxicol Sci. 2003 Aug;74(2):361-8. Epub 2003 May 28. PMID: 12773768
Mady Hornig, M.D Etiologic factors and pathogenesis of autism: evidence from clinical studies and animal models. IOM presentation, Feb 9 2004 Audio only: http://www.iom.edu/view.asp?id=19108
Richard C. Deth, Ph.D. Effects of Mercury on Methionine Synthase: Implications for Disordered Methylation in Autism DAN! 2003 Philadelphia - http://64.202.182.52/powerpoint/dan2003/RichardDeth.htm
Richard C. Deth, Ph.D. A Link Between Thimerosal and the Brain: Can Vaccines Affect Central Nervous System Function? Molecular Psychiatry 2004, Volume 9.
Vojdani A, Pangborn JB et al. Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism. Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):189-99. PMID: 14611720
Jeff Bradstreet, M.D. A Case-control Study of Mercury Burden in Children with Autistic Disorders and Measles Virus Genomic RNA in Cerebrospinal Fluid in Children with Regressive Autism. IOM presentation, Feb 9, 2004
Slides: http://www.iom.edu/view.asp?id=18578
Audio: http://www.iom.edu/view.asp?id=19130
Valsamakis A et al. style='mso-bidi-font-style:italic'>Altered virulence of vaccine strains of measles virus after prolonged style='mso-bidi-font-style: italic'>replication in human tissue. J Virol. 1999 73(10): 8791-7. PMID 10482633 http://jvi.asm.org/cgi/reprint/73/10/8791.pdf
The CDC's original findings before the CDC began to manipulate the data, obtained via the Freedom of Information Act: High risk values for thimerosal injections and a range of neurologic problems, including ADHD, tics, language problems, and autism. http://factsformedia.com/factsformedia/thimerosalstudy.pdf
Excerpts from CDC?s in-house conference: Thimerosal sequelae http://www.nationalautismassociation.org/library/IOM%20Simpsonwood%20in%20bold.pdf
Congressman, Dr. Weldon's letter to the CDC director, available at: http://momsonamissionforautism.org/Autism_Central/Dr_Weldon_Responds.shtml
Institute of Medicine presentation of Congressman Dave Weldon, M.D.
http://www.nationalautismassociation.org/pdf/Weldon.pdf
Geier MR, Geier DA. Autism and thimerosal-containing vaccines: analysis of the Vaccine Adverse Events Reporting System (VAERS). IOM presentation, Feb 9, 2004.
Slides: http://www.iom.edu/view.asp?id=18392
Audio: http://www.iom.edu/view.asp?id=19120
David Baskin, M.D. Relation of Neurotoxic Effects of Thimerosal to Autism. IOM presentation, Feb 9, 2004.
Audio only: http://www.iom.edu/view.asp?id=19124
© copyright 2005 Autism Research Institute
The effects of pyridoxal-5-phosphate on sulfotransferase activity: actions on tyrosyl protein sulfotransferase and phenol sulfotransferase.
Authors:
Rosemary H Waring, Robert M Harris and Victoria L Griffiths, School of Biosciences, University of Birmingham, Birmingham. B15 2TT. UK
Introduction
Sulfotransferase enzymes use PAPS (3?-phospho-adenosive-5?-phosphosulfate) to transfer sulfate residues onto a wide variety of substrates. TPST substrates require sulfation for efficient function while sulfation by SULT 1A1 greatly alters substrate properties, usually decreasing their activity.
a) Tyrosylprotein sulfotransferase (TPST)
Substrates - tyrosine residues on gastrin, cholecystokinin, mucin proteins
- Methods
TPST activity was measured (using gastrin as substrate) with radiolabelled 35S-PAPS as sulfate donor; assays were incubated at 37°C for 40 minutes. All assays were performed in quadruplicate).
Enzyme sources were a) platelet pellets prepared by centrifugation from time-expired platelet packs from the Birmingham Blood Transfusion Service and b) human colon adenocarcinoma HT-29 cells which synthesise mucin proteins and are thought to be the best model for the human g.i. tract. These were grown in McCoys 5A medium supplemented with 10% fetal bovine serum and glutamine/penicillin/streptomycin at 37°C till confluent, then harvested and centrifuged to give a cell membrane pellet. This was resuspended in phosphate buffered saline, then sonicated before assay.
Cells were also grown after confluence for 24 hours with varying concentrations of P5P. P5P was also added directly to the platelet assay (0-2.5ìM) MgCl2 was added at varying concentrations (0-5ìM) before the start of the TPST assay.
Results
TPST activity was present in both human platelets and HT-29 cells. This enzyme activity was inhibited in the presence of P5P (Fig. 1). Direct effects of MgCl2 on the assay are shown in Fig. 2. As can be seen, MgCl2 concentration had no significant effects on the TPST activity of HT-29 cells but activated TPST activity in platelets (there are different isoforms of the enzyme).
The concentration of 0.4ìM P5P was then chosen as showing clear reduction of TPST activity in initial experiments (See Fig. 1). Human platelets were treated directly with this concentration while the HT-29 cells were incubated with it for 24h. Varying amounts of MgCl2 were then added to the assays (see Fig. 3). As can be seen, levels of MgCl2 at 0.5ìM or greater removed the inhibition caused by 0.4ìM P5P. Enzyme assays and Western blotting with specific anti-TPST antibodies showed that P5P did not affect the expression of TPST.
All results were carried out in quadruplicate and are expressed as means ± SD. (SD <= 5.3%).
b) SULT1A1 (Phenolsulphotransferase)
Substrates ? Phenols, catecholamines, flavonoids, steroids.
- Methods
SULT1A1 activity was measured using 4-nitrophenol as a substrate (this also picks up any of the SULT1A2 isoform, although this is only present to a small extent in platelet preparations). Again radiolabelled 35S-PAPS was used in the assay as a sulfate donor. The enzyme sources were cytosols from platelets and HT-29 cells, prepared as before and assayed under standard conditions.
Results
SULT1A1 activity was present in both human platelets and HT-29 cells. This activity was inhibited by P5P (Fig. 4). However, this inhibition was only significant in the platelets; the HT-29 cell SULT1A1 seemed relatively unaffected. Treatment with MgCl2 (1.0ìM) on cells exposed to 1.0 ìM P5P restored the activity in platelets (Fig. 6) but had no significant effects in the HT-29 cells, which in any case were not greatly affected by the P5P (Fig. 4) SULT1A1 activity in platelets was almost unaffected by MgCl2 although SULT1A1 activity in HT-29 cells decreased slightly with increasing Mg (Fig. 5). Our previous studies have shown that the isoenzymes in these tissues have different activities and slightly different properties. Incubation of HT-29 cells with P5P had no effect on enzyme expression, as seen by Western blotting and enzyme activity.
All results were carried out in quadruplicate and are expressed as means ±SD. (SD <= 5.4%).
Conclusions
- Platelet and HT-29 cells show TPST activity which is inhibited by P5P, though only the platelet isoform is greatly affected. This inhibition is reversed by MgCl2 in roughly equimolar amounts.
- Platelet and HT-29 cells show SULT1A1 activity which is inhibited by P5P, although only the platelet isoform is greatly affected. Again this inhibition is reversed by MgCl2 in roughly equimolar amounts.
- Neither TPST nor SULT1A1 expression is altered by P5P, which only affects the enzyme activity directly.
- From the literature, P5P has a pseudo-phenolic structure which is believed to interact with those phenol sulfotransferases for which phenolic rings are a substrate. However, addition of Mg2+ may form a complex which no longer interacts with the enzyme. From the therapeutic point of view, Mg2+ ions should be supplied in at least a 2:1 ratio with P5P to reverse any inhibition and activate those sulfotransferases which respond to increased magnesium levels particularly the platelet enzymes.
Fig. 1 -- Effects of varied P5P concentrations on TPST activity in platelets and HT-29 cells, expressed as a percentage of the control (0ìM P5P).
Fig 2 -- Effects of different MgCl2 concentrations on TPST activity in platelets and HT-29 cells.
Fig. 3 -- TPST activity of platelets and HT-29 cells treated with P5P (.4 ìM) and varied concentrations of MgCl2. Activity is expressed as % control (0ìM P5P, 0ìM, MgCl2).
Fig. 4 -- Effects of P5P concentration on SULT1A1 activity in platelets and HT-29 cells.
Fig. 5 -- Effects of different MgCl2 levels on SULT1A1 activity in platelets and HT-29 cells.
Fig.6 -- SULT 1A1 activity of platelets and HT-29 cells treated with P5P (1.0 ìM) and varied concentration of MgCl2 (Activity is expressed as % control (0 lìM P5P, 0ìM MgCl2).
© copyright 2005 Autism Research Institute