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Radical Induction Theory-Time to re-visit

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Ulcerative Colitis
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Old Mike
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Posts : 4074
Posted 2/8/2015 8:38 AM (GMT -8)
I urge you all to read and understand, not a real difficult read.
Good chance it might be the metabolic cause of UC.

Of course we are still left as to what is the cause of the metabolic problem.

Perhaps why there is not a cure, the metabolic cause in not fixed.

RIT can even perhaps explain why UC starts in the rectum.

Minimal antioxidant defense, continuous oxidant stress, maximal antigenic load.

Sort of what is the cause of the cause of the cause.
But in any event you are being oxidized.


Might be critically important to take butyrate and ALA at the same time.
Butyrate also has many immune modulation, anti inflammatory and bacteria killing properties.
Nettle leaf extract, to knock down TNF, NAC.
ALA or the more expensive R-lipoic acid to quench hydrogen peroxide.
Selenium for GPx







Old Mike

RIT paper-Radical Induction Theory

http://www.wjgnet.com/1007-9327/11/2371.pdf


Patent-gives more info
http://www.google.com/patents/US8476233



one of my old threads think this is the first one, might have 4 or 5 others

https://www.healingwell.com/community/default.aspx?f=38&m=2537173



why FMT might work in some, perhaps it replaces many of the hydrogen peroxide generating bacteria

Many are triggered by antibiotics, perhaps they leave many h2o2 generating bacteria
I also suggest you read the whole paper, some probiotic bacteria can generate h202.

http://www.ncbi.nlm.nih.gov/pubmed/20224151



really might be a good idea to stay away from B6 supplements or food fortified with B6

in its breakdown it generates hydrogen peroxide,you will see it mentioned in the RIT paper

http://www.ncbi.nlm.nih.gov/pubmed/20224151


Gpx chemistry
http://www.sciencedirect.com/science/article/pii/S0304416512002735



If I take arginine I get worse generates more nitric oxide from inos.

If I supplement with SOD I get worse, makes more hydrogen peroxide



NAC might be one of the best supplements,but not absorbed well and lots destroyed in the

gut and liver first pass.

People have tried on the site NAC enema but it burns.

Well I just tried some in my mouth by emptying half a gel cap, taste sour and it burns,so

it is going to burn the hell out of your recutm.

Poor mice when they give it in enema form.

But interestingly enough, teeth felt really clean,which suggests biofilm removal.

Sublingual might get more into the blood,just swish around for a minute or two then swallow

then take the rest of the pill. It is a small molecule so can get through tissue.

If I find anything else of interest, I will add it.


glycine and NAC raises glutathione.
http://ajcn.nutrition.org/content/94/3/847.full

Post Edited (Old Mike) : 4/19/2017 6:24:53 PM (GMT-6)

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UC Dad
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Posted 2/8/2015 9:36 AM (GMT -8)
ferrous sulfate?
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Old Mike
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Posted 2/8/2015 10:19 AM (GMT -8)
Excess iron will cause oxidation via the Fenton/

http://en.wikipedia.org/wiki/Haber%E2%80%93Weiss_reaction

Many are irritated by iron supplements.

Rock and a hard place if anemic.

You will also notice many foods are fortified with iron, as is white flour, and many cereal products.

In one of the papers it talks about iron utilization by e coli.

Perhaps why Nissle 1917 works on some people it sequesters iron from other e coli.

Old Mike

 

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Old Mike
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Posted 2/8/2015 11:56 AM (GMT -8)
Going a bit further, glutathione transferase seems to be low in UC.

Old Mike

http://www.ncbi.nlm.nih.gov/pubmed/7787158

One inhibitor I found, was vitamin E. Yikes. Will look for others.

http://www.ncbi.nlm.nih.gov/pubmed/12781202


increasing with diet

http://www.ncbi.nlm.nih.gov/pubmed/6278195


NAC mouse drinking water

http://www.ncbi.nlm.nih.gov/pubmed/22732651


vitamin c might help,I have taken up to 4 grams a day,no effect but did not take with NAC

http://journals.tubitak.gov.tr/medical/issues/sag-10-40-6/sag-40-6-7-0905-6.pdf


digitoflavone

http://www.molecular-cancer.com/content/13/1/48


ah ha antibiotics certain ones damage mammalian cells via ROS production,cipro,ampicillin, basically the

bactericidal ones, so besides killing gut bacteria this is a double whammy on your gut cells

http://collinslab.mit.edu/files/stm_kalghatgi.pdf


butyrate as an antioxidant peroxides colon cells

http://www.ncbi.nlm.nih.gov/pubmed/11577008

 

Post Edited (Old Mike) : 5/6/2015 8:01:55 AM (GMT-6)

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UC Dad
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Posted 2/8/2015 2:45 PM (GMT -8)
Interesting relationships for sure.
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ExcuseMeINeedToPoop
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Posts : 56
Posted 2/9/2015 8:09 AM (GMT -8)
Thanks for the link to the paper, Old Mike.

Makes you wonder if all the use of H2O2 in our food production might have a factor in some of our suffering. I think much of our food and/or the containers in which they are packed take a bath in H2O2 at some point in their production. And I believe that practice started in the early-ish 20th century. Who knows?

I've taken NAC for headcolds and it seems to help. I'll usually take take 600mg if I feel a cold coming on or if someone in the house is fighting one and I think it works to shorten the duration or help me avoid it altogether. I've taken them for a week at a time but never noticed that they helped with my UC. Most likely 1 week isn't long enough to notice a difference.

Thanks for putting in all this legwork. It's good stuff to be aware of.
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Old Mike
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Posted 2/11/2015 6:28 AM (GMT -8)
Well searching around long enough I ran into a patent by Dr. J Pravda who wrote the radical induction theory.

This is not just some guy off the street, he works here.

Inflammatory Disease Research Centre, West Palm Beach, FL

Tuff read but possibly what is really going on,we are being oxidized first,which sets up the defect in the mucus barrier,then leading to polymicrobial bacterial invasion, bringing in immune cells and cytokines, which then generate more hydrogen peroxide and the more depletion of antioxidant enzymes and tissue destruction.

I also have found that high levels of TNF-A, induce high levels of peroxides.

There also might be a genetic component, which is of course not good.

The patent is so long have not finished it yet.

Please, please, please read this stuff even it is over your head.

This first paper on the RIT radical induction theory, is not to difficult.

Bottom line of all this is that we need to improve are endogenous antioxidant defense, with at least

R-lipoic acid and NAC and perhaps glutathione,and anything else we come up with.

Not sure I agree with vitamin E, seems to inhibit glutathione transferase.

Yes in the past have taken ALA or NAC but not together,

Right now taking NAC, for the last month or so, seems to be helping.

Will have to add ala.

I am not noticing mucus thinning.


Why do I want you to read this stuff.

The explanation looks like what might really be going on in our guts.


Possibly the answer to why UC generally starts in the rectum, we have been looking for this for years.

It is in the middle of the patent, there is more stuff then I have listed here.

Rectum:

The greatest risk factor for ulcerative colitis is the presence of a rectum. Within this area of the colon a junction of physiological parameters converge to increase the potential for H2O2 generation and oxidative tissue damage (induction). Studies have shown that the reducing power (antioxidant capacity) and GSH synthetic rate of the rat intestine decreases distally, reaching its lowest level in distal colon when compared to the proximal small intestine (Blau, 1999). The reducing power of the human gastrointestinal tract likewise decreases from stomach to colon (Roediger and Babige, 1997). The reducing power of the human colon is significantly decreased when compared to the liver with levels of major anti-oxidant enzymes (catalase, superoxide di****ase and glutathione peroxidase) being 4, 8, and 40% of hepatic values respectively (Grisham et al., 1990). However, rectal epithelial cells have the same complement of enzymes, i.e., cytochrome oxidase, xanthine oxidase, etc., as the liver for use in metabolism of foreign substances including alcohol and xenobiotics (Roediger and Babige, 1997). One by-product of this metabolism is hydrogen peroxide that the rectal epithelium is ill equipped to deal with if produced in excess. Un-neutralized excess H2O2 may diffuse to the extracellular space and induce oxidative damage to the colonic epithelial barrier thereby increasing its permeability to luminal bacterial antigens. Any substance found in the body which, through its metabolism, can give rise to hydrogen peroxide in rectal epithelial cells is a positive risk factor for ulcerative colitis induction.


As you might guess, I am real excited about this.

You really need to read the whole patent there is tons of stuff as dietary risk factors,ect.

Old Mike

http://www.google.com/patents/US8476233

 

Post Edited (Old Mike) : 2/11/2015 8:01:10 AM (GMT-7)

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Canada Mark
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Posted 2/23/2015 8:24 PM (GMT -8)
"The high incidence (over 50%) of spontaneous improvement and relapse seen in ulcerative colitis (Meyers and Janowitz, 1989) suggests a reversible disruption"

This partial statement from the opening of the patent you link to I found rather intriguing. Never thought about it from this perspective in regards to UC.

Why do many have extended periods of spontaneous improvement or even complete remission? Whatever is going on MUST be revisable somehow when you really think about it.


-------------

Reference: (From the patent)
The "natural history" of ulcerative colitis: an analysis of the placebo response:
www.ncbi.nlm.nih.gov/pubmed/2646359
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Old Mike
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Posted 2/24/2015 3:23 AM (GMT -8)
Hey Mark:

Yes the placebo effect is strong in UC,wish I knew why, but the whole point is that in some

people the disease can be reversed all by itself.

Anyway here is more stuff on redox status/ROS.

5-asa

http://www.ncbi.nlm.nih.gov/pubmed/21208525

bacteria

http://www.researchgate.net/publication/255788272_Redox_Signaling_Mediated_by_the_Gut_Microbiota

Vitamin D and glutathione status

http://onlinelibrary.wiley.com/doi/10.1111/cen.12449/abstract

Also remember in the SCD diet Elaine wanted people to eat dry curd cottage cheese.

Well cottage chees contains lots of cysteine.


nitric oxide and dysbiotic bacteria

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2008.03612.x/pdf


CoA pantothenic acid def

http://ajcn.nutrition.org/content/21/5/495.full.pdf


CoA blocked in uc

http://www.ncbi.nlm.nih.gov/pubmed/998543



 CoA thiolase inhibition by peroxides, this seems to be the block in butyrate beta oxidation in the colon

http://www.ncbi.nlm.nih.gov/pubmed/17483192


small clinical trial chached version , for some reason the active web page wont let you look at old stuff.

http://webcache.googleusercontent.com/search?q=cache:GthI1XM85RoJ:www.gastroendonews.com/ViewArticle.aspx%3Fd%3DIn%252Bthe%252BNews%26d_id%3D187%26i%3DOctober%2B2012%26i_id%3D889%26a_id%3D21908+&cd=1&hl=en&ct=clnk&gl=us


Old Mike

 

Post Edited (Old Mike) : 5/31/2015 8:20:26 AM (GMT-6)

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Old Mike
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Posted 4/17/2015 5:26 AM (GMT -8)
I cant help myself.
Have to post this again.
Please read the radical induction theory,which I have in the first post,but will also link it here.
Just about everything else you see going on with UC is down stream of initial events.
To me seems to be the real deal in what initiates and propagates UC.

This I believe is the cause of Swidsinski's impaired barrier function.

Now I have some doubts that the mucus can be fully repaired without first eliminating the

initial cause which is excess hydrogen peroxide.

Genetics may play a role in that we are on the low end of GPx production,

if so,coupled with environmental stress/toxins you have excess peroxide,which destroys

the basement membrane and UC manifests.


Swidsinski also says that the biofilm is secondary to an impaired barrier/mucus barrier function.

Wala, excess hydrogen peroxide.

Hopefully this is the answer to the unanswerable question and the idiopathic nonsense can stop.

Old Mike

RIT paper-Radical Induction Theory

http://www.wjgnet.com/1007-9327/11/2371.pdf


butyrate epigenetic effects

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312834/

Post Edited (Old Mike) : 4/17/2015 2:08:35 PM (GMT-6)

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Tunnelvisionary
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Posted 4/17/2015 10:44 AM (GMT -8)
Will take some time to read into the info here.

edit: Is there any info out there on how gut bacteria or antibiotics fit into this theoretical framework?

Post Edited (Tunnelvisionary) : 4/17/2015 12:58:56 PM (GMT-6)

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Old Mike
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Posted 4/17/2015 11:46 AM (GMT -8)
Tunnel: Yes, I have links posted in this thread to your questions.
Many times I link supporting info.

They may not be in any specific order, as I go down a research path, one thing leads to another.

I had the same questions gut bacteria and antibiotics,is there a peroxide link, sure is.
Old Mike

Post Edited (Old Mike) : 4/17/2015 1:53:32 PM (GMT-6)

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Tunnelvisionary
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Posted 4/17/2015 12:23 PM (GMT -8)
Just skimmed the paper by Jay Pravda on the overview of RIT.

This seems really comprehensive and fits everything we've read about UC into a cohesive theory. I came across the article on the small trial on that anti-oxidant enema they gave those 33 patients. The problems other researchers bring up are valid, but that seems like such a dramatic improvement in both groups of patients. Controlled trials would be necessary, but this is exciting.

The only issue I seem to have is why this theory seems to have picked up no traction at all. The last paper posted on this is the one Pravda wrote in 2005.
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Old Mike
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Posted 4/17/2015 3:17 PM (GMT -8)
I don't have any idea why no traction,but can guess.
Too simple. So simple I could cry.
Possibly a big one, not invented here, syndrome.
Of course this and say FMT is sort of off label for UC, it is difficult to go mainstream.
I hate to say it but there is big big bucks behind biologics.
He does have several patents on this,from the patents we can see what he is doing.
He is a GI doc, and not some guy off the street.

I again urge everyone to read this info. Not really difficult to understand.

Boils down to excess hydrogen peroxide in the cells.

I know this is boring stuff to many,but your colon might depend on it.


On a slightly different subject, when you turn grey your hair is being bleached, by hydrogen peroxide.

If your hair turns white you are really being bleached.


OM

more backup to this

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188172/


humans in India depleted

http://www.ncbi.nlm.nih.gov/pubmed/24927343

Post Edited (Old Mike) : 4/17/2015 6:16:16 PM (GMT-6)

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Tunnelvisionary
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Posted 4/17/2015 6:13 PM (GMT -8)
Read half of it more in depth today.

Really find it intriguing how much ground was covered. Why smoking cessation is associated with UC, why sudden decrease in stress would be associated with it (I remember mentioning this in a thread about stress that I made), the effects of long and short term stress, why vitamin D might be helpful, why UC starts in the rectum, why UC doesn't seem to spread beyond the colon, why there is healthy tissue + the differences between healthy and diseased tissue, the genetic contribution.

But under this theory, how would you go about explaining the increasing incidence in the last century? More stress? More people around with factors for increase peroxide production? Would antibiotics/gut bacteria explain increased peroxide production in colon epithelial cells?

The idea is very compelling and I think a good argument is made. Still a tiny bit skeptical, for reasons you stated OM (seems way too simple). Will definitely be reading more into this in the next few days.
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Old Mike
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Posted 4/18/2015 3:10 AM (GMT -8)
Tunnel: You ask the $64,000, I am dating myself here.
Yea I am still a little skeptical myself,but have not found a better explanation.
Barring MAP infection as a cause of UC.
It could be a million things, which are part of industrialization / westernization.
For instance there is diesel engine use around 1900, prior to that there was no microparticles
from diesel combustion, the less than 10um particles can cause increased ROS, as will others.
There was of course a huge amount of air pollution from coal, so who knows.


I find this quite compelling, from one of his patents.

On a populational level, ethnic variation of glutathione peroxidase has been recorded with individuals of Jewish or Mediterranean origin exhibiting lower activities (The Metabolic and Molecular Basis of Inherited Disease, 2001, 8th ed., p. 4650). A two to four fold increase in incidence and prevalence of ulcerative colitis has also been reported for these ethnic groups (Roth et al., 1989).

jewish populations
http://www.jgld.ro/2009/2/22.pdf

Part of the problem perhaps in trying to find a cause/trigger is that the cause might vary with time.

IBD started to increase 1900-1920 ish, well there was no antibiotics or widespread vaccine use at the time.

Today there might be a different set of causes such as antibiotics,so who knows.


He also mentions that homocysteine can knock down GPx by 10 times, well I am on the high

end of normal homocysteine last time I checked.


Of the many theories looked at this one seems to have a real good fit.

Old Mike

Post Edited (Old Mike) : 4/18/2015 8:39:43 AM (GMT-6)

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Old Mike
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Posted 4/19/2015 6:56 AM (GMT -8)
Tunnel: Here is one of my older threads on the subject.
I must have stopped taurine, but after re reading will restart.

Seems to me there is something very wrong with our redox systems, there has gotta be a way to fix it.

Also here is some info on taurine and periodontal disease, perhaps the same thing goes on in the colon.

But at any rate taurine orally made significant changes in redox status in humans.
So far seems what has a chance is Selenium,butyrate,ALA,NAC,taurine, possibly milk thistle,B2.

Part deux is a must read.

Old Mike

http://www.ncbi.nlm.nih.gov/pubmed/24932194


Radical Induction Theory Part Deux
As you can see I was really into this theory, still am.
https://www.healingwell.com/community/default.aspx?f=38&m=2540341
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Tunnelvisionary
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Posted 4/19/2015 10:20 AM (GMT -8)
Finished the initial paper, read it way more in depth and I like what I'm reading. At the very least, it's a VERY compelling argument for the cause of UC, and I'm still impressed by how many observations of what happens in UC are accounted for. The diagram of the radical induction and how the immune system propogates the illness is pretty close in line with what I already thought. I remember mentioning that the immune system causing inflammation is probably better than letting bacteria invade the epithelial tissue and cause sepsis.

There's a possible explanation for why UC starts in the rectum, how it spreads, the immune component, the genetic component, the bacterial component, what is happening in healthy tissue vs diseased tissue, vitamin D connection, compelling explanation for smoking cessation causing UC, stress connection, historical observations, reasons for FMT being hit or miss, extra-intestinal manifestations, why UC can be so difficult to treat yet also have spontaneous remissions, why mesalamine is the most effective treatment, the relative helpfulness and unhelpfulness of our current treatment options...

Part of me wonders why they don't have h2o2 mouse models of colitis, if it more accurately reflects UC. What was really interesting to note was how GPx knockout mice induced colitis that slowly extended throughout the colon.

Will be reading more and more into this. Kinda wanna email Dr. Pravda and see what is going on with his thinking of this theory these days as well. Strange to see that this was published 10 years ago and there is very little mention of it in the research community (only 25 articles cite it according to pub med...over 10 years!)
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Old Mike
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Posted 4/19/2015 10:59 AM (GMT -8)
Oh but there are, but more so in rats, they did hydrogen peroxide in the 50-60's and there tuff
to dig out.
Here is one, I have found others in the past.
OM
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2072729/pdf/brjexppathol00408-0011.pdf

there are also lots of human cases but they usually resolve, just search colitis hydrogen peroxide.

People using as enema, peroxide on scopes causing colitis.


here is something on fecal diversion

http://www.scielo.br/pdf/acb/v25n5/a02v25n5.pdf

Post Edited (Old Mike) : 4/19/2015 1:14:22 PM (GMT-6)

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Old Mike
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Posted 4/21/2015 1:24 PM (GMT -8)
Please don't let your eyes glaze over,not that difficult to understand.

Put it this way, if this system is working right, it looks like it should be shutting down
many if not all of the inflammation paths, and also kill bacteria, and even have a anti biofilm effect.
Even while drenched in TNF-Alpha. If phagocyte derived.

I have to think this is important and a key, to shutting down inflammation.

In addition to taurine might want to also get more bromine into the diet,but that's an aside.

Have add some newer info to the deux thread.

http://www.ncbi.nlm.nih.gov/pubmed/23933994

For more complete info on taurine go here.



Radical Induction Theory Part Deux

https://www.healingwell.com/community/default.aspx?f=38&m=2540341
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Old Mike
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Posted 4/23/2015 5:07 AM (GMT -8)
I see there is little interest in this subject but never the less will keep at it.This is getting curiouser and curiouser.
We make our own taurine but not all that much, get some from the diet depending on how much
meat and seafood you might eat, vegetarians get very very low levels from the diet.
Anyhow there is probably lots of this stuff in our diet today, and phosphatidyl choline or lecithin started to be
produced 1920ish. When hydrolyzed in the gut or elsewhere it turns into lysophosphatidyl choline.
So what.
Well it seems to block the TAUT, taurine transporter.
http://www.tandfonline.com/doi/pdf/10.1271/bbb.66.730


http://en.wikipedia.org/wiki/Lysophosphatidylcholine


Well in UC we might need a lot of taurine to down regulate the inflammatory cascade.
Crohn's there is a defect in macrophage killing ability of ingested bacteria.
Taurine might down regulate this ability even more, but so much other stuff going on
difficult to tell if good or bad.
Will add more on the lyso, if when I find it.
Would love to know if vegetarians have less crohns and more UC.
Seems that a semi vegetarian diet can help crohns,less taurine?
Switching to paleo helps some with UC,more taurine.
SCD not sure what is going on.
Lacto-ovo might be even worse,PC from eggs.
I am not talking about rectal or colon mucus PC,or lack there of.
Old Mike
short version
http://www.ncbi.nlm.nih.gov/pubmed/12036043
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Tunnelvisionary
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Posted 4/23/2015 11:17 AM (GMT -8)
Apologies for the lack of posting OM, still really interested in this, but have been pretty busy (fortunately, it's been a long time since I had real things to do!)

One thought I had in light of this is that attacking the problem of intracellular hydrogen peroxide is one important part of the equation, but I think the inflammatory process has to be taken care of as well. The continuous generation of peroxide from our WBCs as well as the destruction of our barriers from the inflammation would also have to be dealt with too, probably just as important as reducing intracellular peroxide.

I recently found out that I had been deficient in almost all nutrients for a long time now when I had blood tests done while in the hospital. Being deficient in vit D and selenium and other nutrients that may allow cells to take care of peroxide better may have contributed to my UC onset. I remember getting tingly after a night of drinking since a year back now which I found out was due to vitamin deficiencies. None of my friends had ever experienced this, and I had been dealing with an eating disorder which probably lead to this state. Drinking, stress, vitamin deficiencies, genetic predisposition, and antibiotics may have all lead to peroxide creation and lack of sequestration which lead to the destruction of the structures responsible for maintaining the mucus barrier, and then began the process of coming down with UC.

Having humira + lialda are helping but both on their own were not helping as much as they are now that I am attempting to address possible peroxide excess. Have put a hold on drinking for a while (noticed my uveitis would worsen when I had a beer even with all the meds), have reduced stress, and started addressing the malnutrition..

Lots of improvement, but I'm taking it one day at a time. Probably will be on less, but am definitely still reading more about this, and will be sure to keep you updated.

The more I think about it, the more unique observations of this disease are so adequately explained under this theory. It makes so much sense to me, but I am still hesitant to draw any solid conclusions. After all, it could be the humira starting to work too, though even under this theory I think the traditional treatments would be vital to inducing stable remissions of UC once the inflammatory process has begun.

Post Edited (Tunnelvisionary) : 4/23/2015 1:20:14 PM (GMT-6)

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Old Mike
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Posted 4/23/2015 11:25 AM (GMT -8)
Tunnel I suggest you read all my taurine stuff, it would seem to control all the inflammation.
You need to read part deux.
Once converted to TauCl and TauBR, should stop all the ROS,tnf,inos you name it.
Driving me nuts, in the bottom of my guts really believe taurine has to work.
Old Mike
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Tunnelvisionary
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Posted 4/23/2015 11:32 AM (GMT -8)
Will take a look at it, but I would be reluctant to trust that taurine is the key to it all. There's a lot going on here that we can look at theoretically, but would vary biochemically in reality from person to person.
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Old Mike
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Posted 4/23/2015 12:10 PM (GMT -8)
Me too that is why I put up so many papers.

But not theoretical at least in rats,hopefully also in humans.

Its not actually the taurine  but the tauBr and tauBr.

OM

http://molpharm.aspetjournals.org/content/69/4/1405.full


works in vitro on human cells

http://www.ncbi.nlm.nih.gov/pubmed/19222497


TauBr good summay, think I will try and get more bromine into diet.

http://www.biomedcentral.com/content/pdf/1423-0127-17-S1-S3.pdf

Post Edited (Old Mike) : 4/23/2015 2:59:19 PM (GMT-6)

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