Friday, November 6, 2009

Thimerosal: Neurotoxic in a plethora of forms, still used in Hep B, Influenza, H1N1 vaccines

Thimerosal: neurotoxicity is not limited to the autism link as many people assume. Thimerosal is causally linked to a plethora of ND's (neurological disorders), cell death, mitochondrial dysfunction, and more.

http://www.iaomt.org/testfoundation/thimtox.htm

This is a very lengthy article on thimerosal toxicity and it's relevance to vaccinations and brain damage. It cannot be copy/pasted because of the file type but is more than worth the read.

Medical studies on thimerosal:

Mitochondrial dysfunction, impaired oxidative-reduction activity, degeneration, and death in human neuronal and fetal cells induced by low-level exposure to thimerosal and other metal compounds Geier DA, King PG, Geier MR.Toxicological & Environmental Chemistry 2009, 1–15

iFirsthttp://www.informaworld.com/smpp/content~content=a910652305~db=all~order=pubdate

Thimerosal (ethylmercurithiosalicylic acid), an ethylmercury (EtHg)-releasing compound (49.55% mercury (Hg)), was used in a range of medical products for more than 70 years. Of particular recent concern, routine administering of Thimerosal-containing biologics/childhood vaccines have become significant sources of Hg exposure for some fetuses/infants. This study was undertaken to investigate cellular damage among in vitro human neuronal (SH-SY-5Y neuroblastoma and 1321N1 astrocytoma) and fetal (nontransformed) model systems using cell vitality assays and microscope-based digital image capture techniques to assess potential damage induced by Thimerosal and other metal compounds (aluminum (Al) sulfate, lead (Pb)(II) acetate, methylmercury (MeHg) hydroxide, and mercury (Hg)(II) chloride) where the cation was reported to exert adverse effects on developing cells. Thimerosal-associated cellular damage was also evaluated for similarity to pathophysiological findings observed in patients diagnosed with autistic disorders (ADs). Thimerosal-induced cellular damage as evidenced by concentration- and time-dependent mitochondrial damage, reduced oxidative–reduction activity, cellular degeneration, and cell death in the in vitro human neuronal and fetal model systems studied. Thimerosal at low nanomolar (nM) concentrations induced significant cellular toxicity in human neuronal and fetal cells. Thimerosal-induced cytoxicity is similar to that observed in AD pathophysiologic studies. Thimerosal was found to be significantly more toxic than the other metal compounds examined. Future studies need to be conducted to evaluate additional mechanisms underlying Thimerosal-induced cellular damage and assess potential co-exposures to other compounds that may increase or decrease Thimerosal-mediated toxicity.Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts.

Baskin DS, Ngo H, Didenko VV.Department of Neurosurgery, Baylor College of MedicineToxicol Sci. 2003 Aug;74(2):361-8. {free online}

http://toxsci.oxfordjournals.org/cgi/content/full/74/2/361

Thimerosal is an organic mercurial compound used as a preservative in biomedical preparations. Little is known about the reactions of human neuronal and skin cells to its micro- and nanomolar concentrations, which can occur after using thimerosal-containing products. A useful combination of fluorescent techniques for the assessment of thimerosal toxicity is introduced.
Short-term thimerosal toxicity was investigated in cultured human cerebral cortical neurons and in normal human fibroblasts. Cells were incubated with 125-nM to 250-microM concentrations of thimerosal for 45 min to 24 h. A 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) dye exclusion test was used to identify nonviable cells and terminal transferase-based nick-end labeling (TUNEL) to label DNA damage. Detection of active caspase-3 was performed in live cell cultures using a cell-permeable fluorescent caspase inhibitor. The morphology of fluorescently labeled nuclei was analyzed. After 6 h of incubation, the thimerosal toxicity was observed at 2 microM based on the manual detection of the fluorescent attached cells and at a 1-microM level with the more sensitive GENios Plus Multi-Detection Microplate Reader with Enhanced Fluorescence. The lower limit did not change after 24 h of incubation. Cortical neurons demonstrated higher sensitivity to thimerosal compared to fibroblasts. The first sign of toxicity was an increase in membrane permeability to DAPI after 2 h of incubation with 250 microM thimerosal. A 6-h incubation resulted in failure to exclude DAPI, generation of DNA breaks, caspase-3 activation, and development of morphological signs of apoptosis. We demonstrate that thimerosal in micromolar concentrations rapidly induce membrane and DNA damage and initiate caspase-3-dependent apoptosis in human neurons and fibroblasts. We conclude that a proposed combination of fluorescent techniques can be useful in analyzing the toxicity of thimerosal.Thimerosal induces micronuclei in the cytochalasin B block micronucleus test with human lymphocytes.

Westphal GA et al.Georg-August-University, Gottingen, Germany.Arch Toxicol. 2003 Jan;77(1):50-5.

Excerpt: Thimerosal is a widely used preservative in health care products, especially in vaccines. Due to possible adverse health effects, investigations on its metabolism and toxicity are urgently needed. An in vivo study on chronic toxicity of thimerosal in rats was inconclusive and reports on genotoxic effects in various in vitro systems were contradictory. Therefore, we reinvestigated thimerosal in the cytochalasin B block micronucleus test. Glutathione S-transferases were proposed to be involved in the detoxification of thimerosal or its decomposition products. Since the outcome of genotoxicity studies can be dependent on the metabolic competence of the cells used, we were additionally interested whether polymorphisms of glutathione S-transferases (GSTM1, GSTT1, or GSTP1) may influence the results of the micronucleus test with primary human lymphocytes. Blood samples of six healthy donors of different glutathione S-transferase genotypes were included in the study. At least two independent experiments were performed for each blood donor. Significant induction of micronuclei was seen at concentrations between 0.05-0.5 micro g/ml in 14 out of 16 experiments. Thus, genotoxic effects were seen even at concentrations which can occur at the injection site. Toxicity and toxicity-related elevation of micronuclei was seen at and above 0.6 micro g/ml thimerosal. Marked individual and intraindividual variations in the in vitro response to thimerosal among the different blood donors occurred. However, there was no association observed with any of the glutathione S-transferase polymorphism investigated. In conclusion, thimerosal is genotoxic in the cytochalasin B block micronucleus test with human lymphocytes. These data raise some concern on the widespread use of thimerosal.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W81-4DF44GF-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1078617709&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=7296b93ae240e5babf6f09e485dffb27

Thimerosal Neurotoxicity is Associated with Glutathione Depletion: Protection with Glutathione Precursors

http://www.nature.com/mp/journal/v9/n9/abs/4001529a.html

M. Hornig; Neurotoxic effects of postnatal thimerosal; Molecular Psychiatry (2004) 9, 833–845

The developing brain is uniquely susceptible to the neurotoxic hazard posed by mercurials. Host differences in maturation, metabolism, nutrition, sex, and autoimmunity influence outcomes. How population-based variability affects the safety of the ethylmercury-containing vaccine preservative, thimerosal, is unknown. Reported increases in the prevalence of autism, a highly heritable neuropsychiatric condition, are intensifying public focus on environmental exposures such as thimerosal. Immune profiles and family history in autism are frequently consistent with autoimmunity. We hypothesized that autoimmune propensity influences outcomes in mice following thimerosal challenges that mimic routine childhood immunizations. Autoimmune disease-sensitive SJL/J mice showed growth delay; reduced locomotion; exaggerated response to novelty; and densely packed, hyperchromic hippocampal neurons with altered glutamate receptors and transporters. Strains resistant to autoimmunity, C57BL/6J and BALB/cJ, were not susceptible. These findings implicate genetic influences and provide a model for investigating thimerosal-related neurotoxicity.

http://www.theflucase.com/index.php?option=com_content&view=article&id=819%3Aaluminum-in-vaccines-increases-thimerosals-toxicity&catid=1%3Alatest-news&Itemid=64&lang=en

Boyd E. Haley, Ph.D., is Professor Emeritus of chemistry and has published important studies about mercury (eg, 1-3). One of his team's finding documented that a major phenomenon in Alzheimer's-like pathologies could be induced by physiologically occurring levels of mercury (1). A recent essay is titled "Aluminum in vaccination-associated cognitive decline, motor neuron disease, autism" (4). That essay prompted an insightful comment from Dr. Haley, wherein he reports that vaccine-levels of aluminum exacerbate the pathologic potential of vaccinal thimerosal: Dr. Haley explained, "Note that aluminum alone does not cause the abnormal biochemistry and production of neurofibillary tangles as does mercury (and only mercury) due to the specific interaction of mercury at specific sulfhydryl sites in specific enzymes/proteins known to be affected dramatically in Alzheimer’s disease. However, in our studies on neurons in culture we found that aluminum at levels found in vaccines dramatically enhanced the toxicity of thimerosal and mercury cation thereby decreasing the level of mercury required to have the toxic effects."Importantly, some vaccines including many flu shots still contain thimerosal, and many contain one or another of the aluminum compounds used as adjuvants. Thus we repeat: aluminum at levels present in vaccines increases the toxicity of thimerosal, which is ~49.6% ethylmercury by weight. Thus when an infant, toddler, or pregnant woman is injected with a vaccine or a combination of vaccines containing aluminum compounds and thimerosal, the likelihood of adverse effects is increased.

Perhaps we should ask, Why care?

Many media reports assure us that no evidence links thimerosal with neurologic harm. For instance, Melissa Healy of the Los Angeles Times expresses a popular notion by writing, "Many argue that environmental exposures -- in particular, to preservatives used in certain vaccines -- are a key factor in the development of autism. But a wide range of comprehensive investigations has failed to find such a link." (5) Unfortunately, Melissa Healy's glib statement is misleading. However, at least three major studies have found thimerosal injections to be associated with developmental disabilities including autism. Two researchers at Stony Brook medical school found that male infants injected with thimerosal via hepatitis B vaccinations (a) were nine times as likely to be enrolled in special education services, and (b) were three times as likely to have autism -- when compared with male infants who had not been so vaccinated (6-7). Importantly, these findings are consistent with the original CDC study (Verstraeten et al 1999) wherein early live thimerosal injections were associated with autism, PDD, language problems, sleep disorders, and tics (reviewed in 8).

Furthermore, other peer-reviewed studies have documented some of the mechanisms by which aluminum and mercury induce pathologies seen as neurodeneneration (eg, 10-14, 15-17).

Noteworthy: in a recently published study, researchers dared mention that "The demonstrated neurotoxicity of aluminum hydroxide and its relative ubiquity as an adjuvant suggest that greater scrutiny by the scientific community is warranted." (14)Similarly, "Although Thimerosal has been recently removed from most children's vaccines, it is still present in flu vaccines given to pregnant women, the elderly, and to children in developing countries." (17)Needless to say, I and others are perplexed. Why do most vaccinologists and many health officials proclaim the safety of vaccines containing aluminum compounds and/or thimerosal? Why do reporters such as Melissa Healy and spokespersons for the CDC and FDA turn our attention away from peer-reviewed studies demonstrating adverse effects from aluminum and thimerosal? Why must myriad children and their families live with adverse effects of vaccinations whose ingredients cause neurodegeneration and developmental disabilities?

References:1. Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer diseased brainPendergrass JC, Haley BE, Vimy MJ, Winfield SA, Lorscheider FL.Neurotoxicology. 1997;18(2):315-24.

Hg2+ interacts with brain tubulin and disassembles microtubules that maintain neurite structure. Since it is well known that Hg vapor (Hg0) is continuously released from "silver" amalgam tooth fillings and is absorbed into brain, rats were exposed to Hg0 4h/day for 0, 2, 7, 14 and 28 d at 250 or 300 micrograms Hg/m3 air, concentrations present in mouth air of some humans with many amalgam fillings. Average rat brain Hg concentrations increased significantly (11-47 fold) with duration of Hg0 exposure. By 14 d Hg0 exposure, photoaffinity labelling on the beta-subunit of the tubulin dimer with [alpha 32P] 8N3 GTP in brain homogenates was decreased 41-74%, upon analysis of SDS-PAGE autoradiograms. The identical neurochemical lesion of similar or greater magnitude is evident in Alzheimer brain homogenates from approximately 80% of patients, when compared to human age-matched neurological controls. Total tubulin protein levels remained relatively unchanged between Hg0 exposed rat brains and controls, and between Alzheimer brains and controls. Since the rate of tubulin polymerization is dependent upon binding of GTP to tubulin dimers, we conclude that chronic inhalation of low-level Hg0 can inhibit polymerization of brain tubulin essential for formation of microtubules.

2. Reduced levels of mercury in first baby haircuts of autistic childrenHolmes AS, Blaxill MF, Haley BE.Int J Toxicol. 2003 Jul-Aug;22(4):277-85.

Reported rates of autism have increased sharply in the United States and the United Kingdom. One possible factor underlying these increases is increased exposure to mercury through thimerosal-containing vaccines, but vaccine exposures need to be evaluated in the context of cumulative exposures during gestation and early infancy. Differential rates of postnatal mercury elimination may explain why similar gestational and infant exposures produce variable neurological effects. First baby haircut samples were obtained from 94 children diagnosed with autism using Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) criteria and 45 age- and gender-matched controls. Information on diet, dental amalgam fillings, vaccine history, Rho D immunoglobulin administration, and autism symptom severity was collected through a maternal survey questionnaire and clinical observation. Hair mercury levels in the autistic group were 0.47 ppm versus 3.63 ppm in controls, a significant difference. The mothers in the autistic group had significantly higher levels of mercury exposure through Rho D immunoglobulin injections and amalgam fillings than control mothers. Within the autistic group, hair mercury levels varied significantly across mildly, moderately, and severely autistic children, with mean group levels of 0.79, 0.46, and 0.21 ppm, respectively. Hair mercury levels among controls were significantly correlated with the number of the mothers' amalgam fillings and their fish consumption as well as exposure to mercury through childhood vaccines, correlations that were absent in the autistic group. Hair excretion patterns among autistic infants were significantly reduced relative to control. These data cast doubt on the efficacy of traditional hair analysis as a measure of total mercury exposure in a subset of the population. In light of the biological plausibility of mercury's role in neurodevelopmental disorders, the present study provides further insight into one possible mechanism by which early mercury exposures could increase the risk of autism3. Mercury toxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994-2006)Wojcik DP, Godfrey ME, Christie D, Haley BE.Neuro Endocrinol Lett. 2006 Aug;27(4):415-23.In a group of 465 patients diagnosed as having chronic mercury toxicity (CMT), 32.3% had severe fatigue, 88.8% had memory loss, and 27.5% had depression. A significant correlation was found between CMT and the Apo-lipoprotein E4 genotype (p=0.001). An investigation into an additional 864 consecutively seen general practice patients, resulted in 30.3% having evidence consistent with CMT, and once again a significant correlation was found with the APO-E4 genotype (p=0.001). Removal of amalgam mercury fillings when combined with appropriate treatment resulted in a significant symptom reduction (p<0.001)>

4. Aluminum in vaccination-associated cognitive decline, motor neuron disease, autismTeresa Binstock; Sept 28, 2009

http://www.generationrescue.org/binstock/090928-aluminum-als-alzheimer-autism.htm

5. Autism's genetic roots examined in new government-funded studyMelissa Healy, Los Angeles Times September 30, 2009 http://latimesblogs.latimes.com/booster_shots/2009/09/autisms-genetic-roots-probed-by-new-governmentfunded-study.html

6. Hepatitis B triple series vaccine and developmental disability in US children aged 1-9 years Gallagher C, Goodman M. Toxicol Environ Chem 2008 90(5):997-1008.{free online}

http://fourteenstudies.org/pdf/hep_b.pdf

7. Hepatitis B vaccination of male neonates and autismCM Gallagher, MS GoodmanAnnals of EpidemiologyVol. 19, No. 9

ABSTRACTS (ACE)September 2009: p. 659
Stony Brook University Medical Center, NY

PURPOSE: Universal newborn immunization with hepatitis B vaccine was recommended in 1991; however, safety findings are mixed. The Vaccine Safety Datalink Workgroup reported no association between hepatitis B vaccination at birth and febrile episodes or neurological adverse events. Other studies found positive associations between hepatitis B vaccination and ear infection, pharyngitis, and chronic arthritis; as well as receipt of early intervention/special education services (EIS); in probability samples of U.S. children. Children with autistic spectrum disorder (ASD) comprise a growing caseload for EIS. We evaluated the association between hepatitis B vaccination of male neonates and parental report of ASD.


METHODS: This cross-sectional study used U.S. probability samples obtained from National Health Interview Survey 1997–2002 datasets. Logistic regression modeling was used to estimate the effect of neonatal hepatitis B vaccination on ASDrisk amongboys age 3–17 years with shot records, adjusted for race, maternal education, and two-parent household.

RESULTS:Boys who received the hepatitis B vaccine during the first month of life had 2.94 greater odds for ASD (nZ31 of 7,486; OR Z 2.94; p Z 0.03; 95% CI Z 1.10, 7.90) compared to later- or unvaccinated boys. Non-Hispanicwhite boys were 61% less likely to have ASD(ORZ0.39; pZ0.04; 95% CIZ0.16, 0.94) relative to non-white boys.

CONCLUSION: Findings suggest that U.S. male neonates vaccinated with hepatitis B vaccine had a 3-fold greater risk of ASD; risk was greatest for non-white boys.

8. [Synopsis & review]Blockbuster primate Study Shows Significant Harm from One Birth Dose of a Mercury-containing Vaccine By Mark Blaxill; Sept 30, 2009

http://tinyurl.com/y9dvzae

9. Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration Yokel RA. J Alzheimers Dis. 2006 Nov;10(2-3):223-53.

10: Aluminum complexing enhances amyloid beta protein penetration of blood-brain barrierBanks WA et al.Brain Res. 2006 Oct 20;1116(1):215-21.

11: Some aspects of astroglial functions and aluminum implications for neurodegeneration Aremu DA, Meshitsuka S. Brain Res Rev. 2006 Aug 30;52(1):193-200.

12: Nanomolar aluminum induces pro-inflammatory and pro-apoptotic gene expression in human brain cells in primary culture, Lukiw WJ et al. J Inorg Biochem. 2005 Sep;99(9):1895-8.

13. Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction, Maryline Couette et al. Journal of Inorganic Biochemistry (2009) in press

14. Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration Christopher A. Shaw; Michael S. Petrik.Journal of Inorganic Biochemistry (2009) in press

15. Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial pathway Makani S et al. Genes Immun. 2002 Aug;3(5):270-8.{free online}

http://www.nature.com/gene/journal/v3/n5/abs/6363854a.html

16. Thimerosal induces neuronal cell apoptosis by causing cytochrome c and apoptosis-inducing factor release from mitochondria, Yel L et al. Int J Mol Med. 2005 Dec;16(6):971-7.

17. Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursorsJames SJ et al.Neurotoxicology. 2005 Jan;26(1):1-8.

Thimerosol is an antiseptic containing 49.5% ethyl mercury that has been used for years as a preservative in many infant vaccines and in flu vaccines. Environmental methyl mercury has been shown to be highly neurotoxic, especially to the developing brain. Because mercury has a high affinity for thiol (sulfhydryl (-SH)) groups, the thiol-containing antioxidant, glutathione (GSH), provides the major intracellular defense against mercury-induced neurotoxicity.

Cultured neuroblastoma cells were found to have lower levels of GSH and increased sensitivity to thimerosol toxicity compared to glioblastoma cells that have higher basal levels of intracellular GSH. Thimerosal-induced cytotoxicity was associated with depletion of intracellular GSH in both cell lines. Pretreatment with 100 microM glutathione ethyl ester or N-acetylcysteine (NAC), but not methionine, resulted in a significant increase in intracellular GSH in both cell types. Further, pretreatment of the cells with glutathione ethyl ester or NAC prevented cytotoxicity with exposure to 15 microM Thimerosal. Although Thimerosal has been recently removed from most children's vaccines, it is still present in flu vaccines given to pregnant women, the elderly, and to children in developing countries. The potential protective effect of GSH or NAC against mercury toxicity warrants further research as possible adjunct therapy to individuals still receiving Thimerosal-containing vaccinations.

Further studies on thimerosal neurotoxicity:

Dórea JG, Marques RC.Modeling neurodevelopment outcomes and ethylmercury exposure from thimerosal-containing vaccines. Toxicol Sci. 2008 Jun;103(2):414-5;

Mutter J, Yeter D. Kawasaki's disease, acrodynia, and mercury. Curr Med Chem. 2008;15(28):3000-10.

Berman RF, Pessah IN,
Low-level neonatal thimerosal exposure: further evaluation of altered neurotoxic potential in SJL mice. Toxicol Sci. 2008 Feb;101(2):294-309.

Herdman ML, Marcelo A,
Thimerosal induces apoptosis in a neuroblastoma model via the cJun N-terminal kinase pathway. Toxicol Sci. 2006 Jul;92(1):246-53.

Humphrey ML, Cole MP,
Mitochondrial mediated thimerosal-induced apoptosis in a human neuroblastoma cell line (SK-N-SH). Neurotoxicology. 2005 Jun;26(3):407-16

James SJ, Slikker W 3rd,
Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors. Neurotoxicology. 2005 Jan;26(1):1-8

Parran DK, Barker A, Ehrich M.
Effects of thimerosal on NGF signal transduction and cell death in neuroblastoma cells. Toxicol Sci. 2005 Jul;86(1):132-40.

Blaxill MF, Redwood L,
Thimerosal and autism? A plausible hypothesis that should not be dismissed. Med Hypotheses. 2004;62(5):788-94.

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