Sunday, September 10, 2006

BC on Autism Episode 14: From Chelation Quackery to RNA Quackery

Click to Play
Formats available: Quicktime (.mov), Flash Video (.flv)
runtime = 1min 11sec
Just some fun with an old JB vid. Had to get this out of my system before I get into some papers and RNA quackery debunking mode.


At 9/10/2006 1:23 AM, Blogger Bartholomew Cubbins said...

before I get into some RNA talk, I might forward some over to another old blog.

At 9/10/2006 3:27 AM, Anonymous Anonymous said...

I cracked up. I can see that's JB Handley, but the blonde at the end is definitely NOT Lisa.

At 9/10/2006 9:14 AM, Blogger María Luján said...

Hi Bart
How are you?
I wonder if you can be interested in another view of the sam. Please let me know
María Luján

At 9/10/2006 9:57 AM, Blogger Bartholomew Cubbins said...

kev - sure go ahead and shoot.

maria - got your email. Sure, the sam is my favorite. /fun

At 9/10/2006 10:33 AM, Blogger María Luján said...

Sorry, same.

What I am going to present is a "possible" scenario- at least for a subgroup of children with autism-, a " needed to prove properly " one and I propose you as a mental exercise for now, trying to understand a complex situation. I am not going to present the pubmed citations, but I can backup what I am talking about with a lot of them- not from medical hypothesis.
I do think that what generally is being discussed are the so called treatments, but I am very interested on the underlying biochemical process and neurocognitive process and the safer, proper and correct detection and diagnosis- of whatever the medical condition in autism we are talking about.

Therefore, for a moment, allow me to accept the following:
a-There is individual susceptibility to toxicants based on genetics
b-There are biochemical imbalances related to the expression of the genes (in the general expression from transcription to the metabolic pathway involvement), that can be present since birth.
c-The epigenetics plays a role in terms also of compensating mechanisms that can be disrupted.
d-There are developmentally regulated changes in several metabolic pathways, especially those from xenobiotics management
e-There are differences in the immune system related to genetics. Even subtle they can be present since birth.

The key point would be , talking of chelation, the underlying process that produced the accumulation of HM.
Let´s go to the process of xenobiotics detox then.
To excrete properly the xenobiotics-mainly HM
1-all the systems related to the way the body manages xenobiotics must be optimum. From the conjugation to with glutathione up to the excretion as conjugated of mercapturic acid to the Phase I and Phase II of the liver
2-because the normal excretion involves the gut flora /kidney and process of xenobiotics transformation must be excellent at both–at the level of cytochrome 450 for example
3-all the transport with aminoacids of xenobiotics (including metals with charge +2), mobilization and delivery to be excreted must be OK
A clue
J Toxicol Environ Health B Crit Rev. 2003 May-Jun;6(3):279-88. Links
A role for P-glycoprotein in environmental toxicology.Abu-Qare AW, Elmasry E, Abou-Donia MB.
Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

P-Glycoprotein (P-gp) is a transmembrane protein, playing significant roles in the process of drug discovery and development and in pest resistance to pesticides. P-gp affects absorption, disposition, and elimination of different compounds and is mainly expressed in intestines, liver, kidneys, heart, colon, and placenta. The expression of P-gp in the blood-brain barrier (BBB) has been associated with the restricted access of many compounds to the central nervous system. Generated knockout mice by disruption of mdr 1a gene, encoding for P-gp, showed that this protein was expressed in the BBB. The absence or the low levels of P-gp elevated drug concentrations in tissues and decreased drug elimination. P-gp is responsible for resistance of cells to agents, particularly the anticancer drugs, by removing these drugs from cells. Increased expression of P-gp is implicated in decreased HIV drug availability at certain intracellular sites. The role of P-gp in affecting efficacy and toxicity of environmental toxicants such as pesticides and heavy metals has not been adequately investigated. Studies showed that P-gp contributes to resistance to pesticides in certain pest species, and to decrease toxicity by removing compounds from cells in mammals. Placental drug-transporting P-gp plays a significant role in limiting the transport of toxicants such as potential teratogens to the fetus. Several in vitro or in vivo assays, including using P-gp knockout or naturally deficient mice, were described for testing P-gp modulators. The role of P-gp following concurrent exposure to more multiple compounds needs further research. P-gp modulators should be carefully used, since some modulators that reverse P-gp efflux action in vitro may lead to alterations of tissue function and increase toxicity of xenobiotics in normal tissues. Recent reports from the pharmaceutical studies on the significance of P-gp as transporters in altering the efficacy and toxicity clearly highlight the need for further research in interaction with environmental toxicants.

Pg glycoproteins is a member of the ABC transporters group, that have been related to ASD- in terms of genetics.
Therefore I wonder, what about ABC transporters levels in children with ASD and physiology, needed to manage properly xenobiotics? Where are the studies about ALL this to discard transport/mobilization problems of xenobiotics? How does affect the presence from dipeptides to longer peptides the transport? How is this related to GI malfunction and gut malfunction/mucosal/flora status in ASD children?

In the management of xenobiotics, factors affecting the toxicity of reactive metabolites are
1-Levels of activating enzymes
2-Levels of conjugating enzymes
3-Levels of cofactors or conjugating chemicals. Glutathione depletion potentiates covalent binding and hepatotoxicity…Reduced glutathione plays an important protective role rapping electrophilic metabolites and preventing binding to hepatic proteins and enzymes.
There is an entire chapter in the “Textbook of Modern Toxicology” from Hogson-2004- dedicated to Chemical and Physiological influence on xenobiotics metabolism.: Nutritional effects, Development (Phase II reactions are age dependent: for example glucuronidation, glycine levels are low the first 8 weeks in human, Transcripted “Glutathione conjugation may also be impared, because of defficiency of available glutathione”) In this book there is a figure of how there is a developmental pattern of glutathione S-transferase activity in female rats from 1 to 140 days life ( from near 5 nmoles/minml to 75 nmoles /minml).. The chapter (163-202) concludes:
The toxic sequelae will vary with developmental stage, nutritional status, health or physiological previous status.
In sequence, from the reaction between a xenobiotic and glutathione, several enzymes are involved: glutathione S transferase-(GSM), gama glutamyl transpeptidase, cisteynil glicinase, N acetyl transferase and finally conjugates with mercapturic acid is formed. This sequence needs adequate levels of essential amino acids, pantothenic acid for Coenzyme A and phosphorus for the synthesis of ATP.
So I wonder if besides/ beyond glutathione , that needs aminoacids , the transformation to mercapturic acid somewhat can be hindered because of problems in some of these enzymes or nutritional problems affected by genetics and epigenetics in ASD?

Considering ASD children are different in biochemistry/physiology since birth- however many of them in the natural genetic variation- I do think that one or several of the detox enzymes or cofactors can be inmature. Also the BBB, especially in children whose brain structure and cytokines/neurotrophic factors are different, making them vulnerable, especially the first years to environmental insult (there are recent published manuscripts about how BBB is more permeable than thougth before and how is affected by heavy metals). This different immune system also makes them vulnerable to antibiotics ( in terms of gut flora weakness) and vaccines (especially to the combined insult because of a crowded schedule) and environmental insult ( what we breath, drink,eat and what we touch).
Therefore I consider that the axis transport system-detox system-antioxidant system-immune system- gut-brain is extremely important and has not been studied in a systematized and enough complete way in ASD to deny an impact in the xenobiotics management, postnatally.

If a problem of transport-involving proteins- is present in ASD a proper method of testing must be developed.
If a problem of transport is present, with a proper method of testing, xenobiotics would show without a chelator.
If a proper method of testing of transport problems in ASD is developed, with diffferent clinical presentation that the NT poisoning of HM, I do think that this would be an important step of testing in ASD, especifically for HM, before any discussion of treatments.

Where are the manuscripts dealing with the study of these problems in ASD?In general I see the discussion that chelation is not a treatment of autism (that is not), but where are the efforts to understand the anecdotical evidence in a systematized and serious way, considering all the analysis I present you above- and I am not a doctor- by the mainstreamed science-toxicologists, inmunologists, biochemists working in ASD?
María Luján

At 9/10/2006 11:07 AM, Blogger notmercury said...

HOLY CRAP! Coffee all over the keyboard! ROTFLMAO

Was that the "Hoff" or the "Hand?"

At 9/10/2006 11:19 AM, Anonymous Anonymous said...

Hmmn... how many trials will it take before NotMercury learns to swallow his coffee before watching/reading blogposts?


At 4/22/2007 5:41 AM, Anonymous Anonymous said...

I've just been through this blog, and get the sad impression that there is a whole world of rip-off artists associated with child autism.
We are giving all the usual bio-meds to our child, they are definitely making a difference, so maybe we've been lucky? I don't know. It is equally sad that the most vulnerable people in society are the ones with the greatest needs.

At 7/19/2007 9:11 PM, Blogger Uncle Dave said...

Cracking up!!!

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