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Defective mucus sugar. Chicken or the Egg problem perhaps solved

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Posted 9/25/2013 12:35 AM (GMT 0)
Incredible thinking Mark: Guess I need to reread that paper.

One of my favorite old star treks is the Tholian Web same type of thing going on.

Link

Think you might like this paper which I just found,have not read it yet.

This discusses bacteria protease and how it is blocked by glycosylation,also read about figure 8 and

mouth bacterial cleavage of colon mucus. This protease can dissolve the inner mucus when not fully

glycosylated,these bugs can also live in the colon.

This begs the question as to why the mucus would not be fully glycosylated.

Will pick this up in the am,really feel a need to go brush my teeth again and use the water pic.

Old Mike

http://www.jbc.org/content/early/2013/04/01/jbc.M113.459479.full.pdf

 

Post Edited (Old Mike) : 9/24/2013 7:10:20 PM (GMT-6)

Posted 9/25/2013 1:15 AM (GMT 0)
The star trek thing is awesome... exactly.

So an attack could come from one side of the web or the other.... genetic (immune) or bacteria. Or both. Just the effect is a loosening or thinning of the web structure.
Posted 9/25/2013 1:38 AM (GMT 0)
One last comment for tonight,took 2 scoops of whey again,plus 3 extra grams of threonine for a total of 5.4 grams plus what comes from food.
Last few days I notice thin mucus,I am thinking where is the thick stuff. But it has now occurred to me that you can't get the thin mucus unless you first have the thick inner mucus.
So perhaps this is good,not seeing gobs of it like before.
The way it works is that the thick inner mucus expands and creates the thinner outer mucus
where the bacteria live.
OM
Posted 9/25/2013 3:06 AM (GMT 0)
I know you guys are excited about this find, but how do you reconcile the fact that the mice in the 4-amino-acid-supplement paper experienced no clinical improvement of their colitis? You might get more mucus out of this, but if you get no relief of symptoms, or no steps toward remission, why do it? (Sorry if I burst your bubble; I hope I just missed something in the reading of that paper. I concluded it was purely an academic exercise).
-GZ
Posted 9/25/2013 11:39 AM (GMT 0)
Hi Guts: I knew someone would ask that question. My guess as to this answer is that they never stopped the DDS, as far as I can tell so the colon cells never had a chance to recover from this chemical,regardless of the increased mucus.
Old Mike

This one leads me to believe we have a problem with the mucus barrier.

http://www.ncbi.nlm.nih.gov/pubmed/23426893

this one shows us visually what is going on

http://www.charite.de/arbmkl/themen/ubersicht/polensascha.pdf

Post Edited (Old Mike) : 9/25/2013 7:30:15 AM (GMT-6)

Posted 9/25/2013 12:08 PM (GMT 0)
I believe it says in the paper the same thing that Mike says - treatment was continued for a period of days. Also I think that one of the points Mike was trying to make earlier was maybe there's a need to get on top of it from a few ways or directions at the same time.

This actually brings up another point though. On other studies as well do they always continue to induce DDS Colitis constantly throughout the time period and study the effects of various treatments under these conditions? Or have they ever induced Colitis and then compared how long it takes to resolve (or if it even resolves) on it's own versus meds or whatever they are curious about.

In other words does DDS induced Colitis go away once they stop inducing it/dosing for it - or does it continue to spiral out of control?
Posted 9/25/2013 12:25 PM (GMT 0)
Have not read this yet but there are at least two models of DSS induced colitis,acute and chronic.

Believe if they do not induce chronic then the mice start to recover,not sure how full the recovery is.


OM

http://jaxmice.jax.org/literature/factsheet/FS0074_Chronic_Mouse_Model_of_IBD_Induced_by_Dextran_Sulfate.pdf

traps and tricks to DDS induced colitis

http://www.hindawi.com/journals/bmri/2012/718617/

Post Edited (Old Mike) : 9/25/2013 6:30:17 AM (GMT-6)

Posted 9/25/2013 1:44 PM (GMT 0)
Thanks for pointing out that they never stopped DSS. So, what we need, then, is for these guys to take some muc2(-/-) mice (the ones that don't create much mucus), let them spontaneously develop colitis, and then try the amino acid therapy to see if there is clinical improvement. I doubt anyone would do this, because it wouldn't result in a new drug that someone could use to make their millions.
Posted 9/25/2013 2:12 PM (GMT 0)
Not to sure how that would work,if the muc2 genes are knocked out then you could give them
all the threonine they need and still not make muc2. However there are other mucins besides muc2
that might take over and protect.
Old Mike
Posted 9/25/2013 3:03 PM (GMT 0)
Have not finished reading yet.

OM

Mucin-type O-glycans and their roles in intestinal homeostasis

http://glycob.oxfordjournals.org/content/23/9/1026.long

this also good on inhibitors

http://www.ncbi.nlm.nih.gov/books/NBK1938/

one of the inhibitors is chlorate,which can be found in food and water,they say no danger

but,but but they are not looking at glycation

http://www.epa.gov/oppsrrd1/REDs/factsheets/inorganicchlorates-fs.pdf

Post Edited (Old Mike) : 9/25/2013 9:28:48 AM (GMT-6)

Posted 9/25/2013 3:20 PM (GMT 0)
I believe there's quiet a few MUC genes and they do some sort of balancing act.. Lot's of info in these for Cystic Fibrosis. One paper I read mentioned that a lack or knockout of MUC 2 caused an increase in MUC1 or something like that or MUC one took over type of thing. Anyway CF has tons of info on all the genes and their effects.

Also they study these genes for CF not in lungs of mice - but in the intestines of mice - so their research/treatments/ideas would apply I would think.
Posted 9/25/2013 3:37 PM (GMT 0)
Also they study why it's thick... which is what kills people with CF.

This brought about another thought though - Since we make mucus in or lungs, eyes, nose and all over the place in our bodies - and I even recently read that it incorporated into cartilage (think arthritis) - with all of these places drawing the need for some pretty specific proteins one could easily see how we could perhaps become deficient.

Also I was wondering if say there isn't enough threonine would the body substitute it with something else? Another protein that would give rise to an odd shape or higher permeability. Or would it just be a matter of not being able to make enough mucus and keep up and therefore say in the colon the lining gets very, very thin - which would lead to penetration.
Posted 9/25/2013 6:31 PM (GMT 0)
Mike you need to read this: ajcn.nutrition.org/content/73/6/1131S.long Microbial modulation of innate defense: goblet cells and the intestinal mucus layer1,2,3

I walked away with a bazillion different thoughts - but two overwhelmed me:

1) A large overgrowth of any one type of bacteria (commensal or pathogenic, does not matter) would be totally brutal to the mucus layer

2) A new reason for the three main amino acids is perhaps the types of sugars that attach to them to form the walls of the web so to speak. Each type of wall is geared towards the effects of certain bacteria in degrading a specific wall type - so a mix of these would give good natural protection as eventually they bump up against a wall that is hard to break down and pass through. To much degradation of one particular wall type could deplete the reserves of one of the specific amino acids... Or something along these lines. So maybe it's a matter of helping out a little via supplementing of a specific type - though you'd never really know which AA unless you knew what type of bacteria had immense overgrowth.


PS - Another lady posted about hormones - and one more about developing UC after giving birth. I was looking for the effects of hormones on mucus production when I stumbled across the above paper. But also came across this:

www.ncbi.nlm.nih.gov/pubmed/9815038

This an a few others suggest there' quite a link between hormones and mucus production. Again that's the way most birth control pills work. Adjusting/altering cervical mucus.
Posted 9/25/2013 6:45 PM (GMT 0)
OHH - And it also supports the thought I had that mucus expansion or the change between the "tightness" of the first layer and the "loosening" of the second layer may come from influences from the luminal side rather than a chemical change in the body of some sort. It touches on the fact that germ free mice have really thick layer of mucus that is perhaps not degraded by bacteria. Which is exactly what I was thinking.

So again, a huge increase in any one type of bacteria and wham.. things go wrong, the body can't keep production up, etc etc etc
Posted 9/25/2013 6:57 PM (GMT 0)
Haha - Although this thesis suggests the point I made directly above is not the case and that it undergoes expansion via host produced enzymes. So who knows.

It's a must read as well - as it spells out why UC is a mucus problem and answers the DDS colitis question much in the same way as the initial event paper.

/gupea.ub.gu.se/bitstream/2077/20050/1/gupea_2077_20050_1.pdf
Posted 9/25/2013 7:13 PM (GMT 0)
HOLY SHI% BALLS !!!!

Stop reading anything else and start reading this asap: www.ncbi.nlm.nih.gov/pmc/articles/PMC1774597/

In a population of 60 patients with chronically active disease, the efficacy of the PC was astoundingly good over a three month treatment period. Compared with a response of 10% in the placebo arm, 90% of the phospholipid treated group responded and 53% were in remission after three months of therapy. No clinically significant side effects were noted. Is this too good to be true?

I haven't read anything other than this... maybe I should but 90% is HUGE.... and over a 60 patient base.... Holy shi@

Edit:
And this: www.ncbi.nlm.nih.gov/pubmed/19504612

Post Edited (Canada Mark) : 9/25/2013 1:22:03 PM (GMT-6)

Posted 9/25/2013 7:21 PM (GMT 0)
Extremely interesting except for the fact that this is 8 years old. Seems like if they were on to something it would have made more progress over these 8 years.
Posted 9/25/2013 7:25 PM (GMT 0)
www.ncbi.nlm.nih.gov/pubmed/23295697

except for this 2012 review....


As the other paper states the glycans are much more the rock stars and getting the attention.

EDIT and this! 2013: www.ncbi.nlm.nih.gov/pubmed/23585269
Posted 9/25/2013 7:28 PM (GMT 0)
All good stuff Mark,I have read most except the last one,still going through that.

But yes the mucus modulates the bacteria and the bacteria modulates the mucus.

And yes we probably have different types of colon mucus cores to stop the 10000 different bacteria from penetration.

I think it is in this paper where it says, something to the effect the mucus allows the immune system to basically

ignore all the trillions of bacteria sitting right next to the colon wall, which would love to get in and infect.

It also says that in a healthy stool on the outside there is no bacteria. Why the stool is coated with mucus, in UC

the stool is covered with antibodies.

I know the analytical tools to do this science are not that old,but my god I really think they could have/should have

figured this out 50 years ago.

Old Mike

http://www.charite.de/arbmkl/themen/ubersicht/polensascha.pdf

Posted 9/25/2013 7:33 PM (GMT 0)
Seems this is a topic that's been discussed on here before... delayed released phosphatidylcholine
Posted 9/25/2013 7:34 PM (GMT 0)
Sorry to burst that bubble,we all thought it was great news when it came out, a few here have tried the treatment

got the pills from Germany or wherever ,little to no effect.

Some of us like myself did some PC enemas,no help for me.

You can search on this site for enteric coated PC or perhaps rPC.

OM

Posted 9/25/2013 7:40 PM (GMT 0)
And something is coming down the pipeline here in regards to a potential treatment:

www.prnewswire.com/news-releases/lipid-therapeutics-licenses-european-rights-to-its-lead-product-lt-02-to-co-development-partner-dr-falk-pharma-gmbh-141872633.html

Though it may be scamish... may now... not sure. But it's recent (2012)
Posted 9/25/2013 7:42 PM (GMT 0)
darn....

Maybe it;s worth keeping an eye on though...

In any case again it supports the mucus barrier breakdown thing and need to supplement and restore it along with other therapies perhaps. The combined approach you mention.
Posted 9/25/2013 7:44 PM (GMT 0)
Not a scam. Whether or works or not is another question.
Posted 9/25/2013 7:54 PM (GMT 0)
You know... When you think about it. A diet very high in fish/shell fish and fatty acids and butyrate and all that stuff might be a good addition as well as trying to supplement the proteins.

Give the body all it could possibly ever need to generate proper mucus.
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