Methylene blue to rescue our mitochondria?

[adec]

[quote="eml256"]Brian, have been aware of this individual's writings about uridine in connection to ALS --find it intriguing and wondered why it was never followed up. She has written about this more extensively on other sites, though I do not have access to my files at present to llink them here:
*http://www.als.net/forum/topic.asp?TOPIC_ID=433&SearchTerms=uroporphyrin[/quote]

Very interesting. I understand this researchers exasperation. What use is it throwing down the gauntlet if there's no one to grab it. I continue studying and adding information as time permits and my limited understanding of a largely complex issue. I will try to contain as much practical information in a single place. I believe purine and Pyrimidine synthesis is the most important topic currently on the board. I have now seen very strong (anecdotal) evidence of its curative effects.

The problem with CoQ10 supplementation remains that as we age mitochondrial proliferation is less likely than an overall increase in mitochondrial size.

The pathway for an important number of amino acids is the synthesis of purine and pyramidine nucleotides. Without sufficient nucleotides there would be little energy to drive a wide variety of biochemical processes. The old theory stated (wrongly perhaps) that dietary nucleotides were unnecessary, even in the diseased. Except.... with age, and especially in a diseased state, the ability for the human body to produce nucleic acids decreases. The complex synthesis of purine and pyramidine is already energy intensive enough whereas there's limited amount remaining for metabolism, for instance: DNA replication and RNA transcription.

Sure proteins carry out chemical reactions; sugars transfer and store energy; and lipids keep separate the inside and outside of cells. Of all these major organic compounds nucleic acids are the most neglected for study (and certainly lipids are the least understood.) Nucleic acid polymers, such as RNA, take a scientific backseat to proteins while each containing an equal amount of structural complexity.

Without that strong carbon-hydrogen bond we'd cease to exist, as inorganic beings. I'd also like to make a strong case for the bond between nucleotides and nucleosides, purines and pyrimidine.

Pyrimidine synthesis also produces beta-alanine (a breakdown product of carnosine) and helps reduce cell damaging oxidative stress: ROS (reactive oxygen species.) Purine is broken down into uric acid also a ROS reducer. I'm sure one could easily find many other positive correlations Obviously too much uric acid causes kidney stones. The need for balancing with nucleosides is equally as important. Granted, nucleic acids such as adenosine protectively increase its normally low value with rapidity under great stress: for instance, due to under inflammation, ischemia, and injury.

Purines are actually larger double-ringed nucleobases, while pyrimidines are smaller and single ringed. Two purines paired are too close for hydrogen bonding, two pymadines are too far apart. Purine bonds are the perfect compliment to pyrmidines. The proper geometrics, conformations, helical structures allows them to hydrogen bond more stably. While those mispairing from the natural configuration can lead to termination of DNA and RNA during transcription. DNA/RNA during transcription or reverse transcription of RNA/DNA genome.

Interestingly, vital dyes such are methylene and tryphan blue are used to measure cytotoxicity in the lab. Only compromised cells with their weakened membranes would allow access to a dye stain.

The need for nucleotides are equally as important. Nucleosides are created by adding a specific sugar (ribose) to a nitrogen base, while phosphates added to this nucleoside creates a nucleotide. Cytotoxicity would occur when enough purine and pyrimidine nucleosides are converted to nucleotides, in their absence. This cytotoxicity increases necrosis, or a decrease in cell viability, and eventual apoptosis or cell death. This further shuts down cell metabolism and weakens cell membrane integrity.

My understanding is the fatter the nucleoside and nucleotide (bigger more stable ring) the greater capacity for a stronger purine-pyrimidine bond. Enough deviations from natural purine/pyramidine synthesis results in termination of DNA and RNA sequencing, and thus form mutations or aberrations. It's my belief this has implications in not only cancer therapy, but likely mitochondrial dysfunction. Fattening those nucleic bonds as opposed to inhibiting DNA transcription and replication (current chemotherapy) is perhaps the better answer.

Interestingly, oral nucleosides produce high nucleoside plasma levels, albeit with a very small concentration in the liver. While oral nucleotides produce higher concentrations of nucleosides in the liver. Purine is musty synthesized in the liver, while pyrimidine is limited to other tissues. The liver is the organ most able to convert simple sugars and aminos to complex molecules, such as involved in pyrimidine and purine sythesis

BTW, I was mistaken about uridine and inosine's competition. It's actually cytadine of which inosine very strongly inhibits along the same pentose pathway. I'm not sure it's important to take easy away from one another.

I'm also focusing tons of energy on pulsed electromagnetic therapy or PEMF. I've experienced huge curative effects over a good period of time now.

[adec]

Anyone who wished to give this theory a whack.... I'd try supplementing with these today.

Nucleotide Complex (RNA/DNA)
=================================
Blue Bonnet manufactures this nucleotide/nucleoside formula made from torula yeast, containing adenosine, cytidine, guanosine, and uridine, along with nucleic acids. You can find it for $20 for 30 caps, and $40 for 60 caps, at places like iHerb.com.

Magnesium orotate
================
The cheapest source is found in a bulk powder at beyondacenturyonline.com. They sell 200 grams bottles for $19.75.

Alpha-GPC
=========
The cheapest source is found in a bulk powder supplied by 1Fast400. Solidnutrition.com is selling 50 grams for $20.44 and 150 grams for $53.39. 600mg, 1-2x daily should be fine.

Triacetyluridine:
============
Cardiovascular Research Ltd of Concord, CA manufactures a dietary supplement brand of triacetyluridine in bottles of 60 capsules, 25mgs each. You can find this product being sold at Bayho.com for $20.35 and Nutrimedical.com for $16.16. 25mg 1-2x daily should be fine.

[Biologist]

Interesting article on, what I assume, is the same molecule:

*http://www.sciencedaily.com/releases/2009/07/090727191249.htm

It certainly shows that this is bioactive stuff...

Biologist

[tyyosh]

Not sure if this contributes to the discussion or not.

Stumbled upon this 2002 document where they describe the use of triacetyluridine in "mito" patients. It appeared to have significant results but at much higher dosages than the 25mg supplement discussed here (which I am now taking thanks to this thread).

*http://www.freepatentsonline.com/EP1171137.pdf

For example, "Example 3" patient on page 8 was given 0.05 g/kg/d, which for an 80kg man is 4 grams, if my math is right.

Some small children were given 2 g/m2 PO TID. (After much googling, I determined that for an adult my size this would be 4 grams orally three times a day, after using a body surface area estimator webpage to determine about 2 square meters of body surface area given height and weight.)

These magnitudes seems like a huge difference from the 25mg supplement. Does anyone know of any recent developments on availability of bulk sources that might make higher dosages possible, or have any thoughts the use of other compounds (Alpha-GPC, Citicoline, others?) to bump up uradine?