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Defective mucus sugar. Chicken or the Egg problem perhaps solved

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Posted 9/21/2013 1:20 AM (GMT 0)
Mark is this what you are reading,if so these are messed up mice with deleted genes.

Simply by eating mucin it had great therapeutic value.

Sounds pretty good to me.

I have no idea how it might work,did these mucins reach the colon intact and protect somehow.

How did the mucins get through normal digestion.

I somehow doubt they did. But perhaps the extra amino acids from the digested

mucin got into the blood stream and fed the remaining mucus generating cells. Of

course might sound farfetched using only 50mg.

Or did the mucins induce some form of oral tolerance.

Believe it or not at one point I tried eating sausage caseings,when oral tolerance was all the rage.  Could not bring myself to eat tripe. Might have to look at tripe again.

The thought of eating colon mucus is actually to me worse than FT.

Of course tripe is probably cleaned of mucus.

Old Mike

Oral administration of exogenous mucin in EPI T-SYN^~ mice. The inventors' experiments demonstrated that O-glycan-deficient mice showed a significant reduction in Muc2 staining, a reduced intestinal mucus gel layer, and high susceptibility to ulcerative colitis. Because secretory mucins are the major components of the intestinal mucus gel layer, they reasoned that administration of exogenous mucins might be therapeutic. The inventors therefore tested whether oral administration of purified porcine stomach mucins could prevent ulcerative colitis in Epi T-syri-/- mice. Epi T-syn-/- mice were treated with 50 mg mucin/mouse/day in Napa-Nector, a commonly used hydration source. The control Epi T- syn -/- mice were treated with Napa-Nector only. Mice were treated for seven weeks beginning at 4-weeks old. Treated mice developed a much less severe form of colitis compared to the untreated controls. Although preliminary, the experiment suggests that loss of O-glycans primarily affects the function of the mucus gel layer, and exogenous mucins are of great potential therapeutic value for the treatment of ulcerative colitis (FIGS. 9 A-D).

Posted 9/21/2013 1:38 AM (GMT 0)
So should we be taking mucin or what?
Posted 9/21/2013 1:49 AM (GMT 0)
Yeah that was were I read that - and one other place a s well.

Been a LOT of reading today... far to much for me. But I see your point now that you mention it.

Maybe there is a way that will bring about spontaneous remission - I wish I could find something on this, but I have not so far. It sure is darn intriguing though. I also recall something about needing replacement from both sides as well - so the gut lumen side and the blood side. So a two pronged approach for some reason.
Posted 9/21/2013 1:50 AM (GMT 0)
Not sure where you are going to get it,still looking.

But here is a related patent on threonine.

It makes mention of this,that threonine is used for inflammatory proteins at the expense of mucoprotein synthesis, that's scary.

These results clearly indicate that the threonine bioavailability in the culture medium can significantly influence the mucoprotein synthesis rate in vitro. Thus, whatever the disease state considered (Inflammatory Bowel Disease, infection, Crohn's disease, or other like disease states), the threonine requirement is increased for the synthesis of threonine rich inflammatory proteins at the expense of the mucoprotein synthesis. Thus, threonine supplementation can be an efficient and effective nutritional intervention to stimulate or to restore the mucoprotein synthesis rate, and thus to facilitate improved epithelial cell protection

Old Mike

https://www.google.com/patents/WO2001056405A2?cl=en&dq=A+method+for+maintaining+or+improving+the+synthesis+of+mucins&hl=en&sa=X&ei=g_o8Uqe8MZjd4AON5IHYBA&ved=0CDkQ6AEwAA

Post Edited (Old Mike) : 9/20/2013 8:03:45 PM (GMT-6)

Posted 9/21/2013 2:08 AM (GMT 0)
Well Freddy,here you go pig stomachs and breast milk.

Still trying to figure out if mucins are in whey.

OM

http://www.acs.org/content/acs/en/pressroom/presspacs/2011/acs-presspac-april-25-2011/pig-stomach-mucins-are-effective-as-anti-viral-agents-for-consumer-products.html

bovine beta casein and humum mucin

http://www.inra.fr/en/Partners-and-Agribusiness/Results-Innovations-Transfer/All-the-news/A-bioactive-peptide

more on beta casein

http://www.betacasein.org/?p=variants

Post Edited (Old Mike) : 9/20/2013 8:39:50 PM (GMT-6)

Posted 9/21/2013 2:14 AM (GMT 0)
Come on... I was so just going to go to bed!

Now I have to learn what the heck threonine is.... Although I remember this from the first patent and looking it up for some reason earlier but have since forgot...

EDIT: oh yeah, now I remember why it caught my interest- I was going to mention that Dr. Stein recently said to me that for some people they need really, really large doses of Tryrosine for a reason in which they are not sure why. He said he thought that multiple genetic defects are present and this sometimes causes the need for excessive amounts of tryrosine to balance out. He also said at the same time 5HT plays a role so as you increase trysoine at a certian point you need to also include a little more 5htp - so they have a supplement called Replete Extra that they give to people in this situation. It has 1,000 mg of tyrosine and 300mg of 5HT. Anyway on my last dosage change he had me adding 4 of these capsules twice per day... Honestly I think it may have made a slight difference. Not sure yet though. I'll see how the next two days go.
Posted 9/21/2013 2:28 AM (GMT 0)
Yea Mark I am about wiped. Enough is enough for today.

We have been doing threonine for a few years, at least InSoFLa has.

I see you don't read all my threads.

I did my scoop of whey today with,an extra 2 grams of threonine, I have the pure amino acid in bulk.

Along with teaspoon cinnamon and now 500 mg of rosemary extract which just arrived today.

Trying to drive down NO,Nf-Kappa Beta,tnf-a,increase mucus.

Also of course many are allergic to milk protein,which is also related to UC.

Now I start to wonder,that the cure is out there,but no one is really saying anything.

These patents are sort of useless,whey with extra threonine,anybody can do that,but the info is good.
OM

Post Edited (Old Mike) : 9/20/2013 8:55:49 PM (GMT-6)

Posted 9/21/2013 3:12 AM (GMT 0)
I was just looking down this road a little on the effects of tyrosine on mucins..

"Mucus hyperproduction in pulmonary obstructive diseases results from increased goblet cell numbers and possibly increased cellular mucin synthesis, occurring in response to inflammatory mediators acting via receptor tyrosine kinases (RYK) and tyrosine phosphorylation (Y-Pi) signaling pathways. Yet, increased mucin synthesis does not lead necessarily to increased secretion, as mucins are stored in secretory granules and secreted in response to extracellular signals"

Probably doesn't have much to do with anything though... though this paper does show that there is a few pathways to mucin production, and that certain amino acids activate these pathways - Mucus hyperproduction would be a good term to describe what I've had going on for some time now. Excessive and crazy amounts of mucus. It's actually pretty disgusting. Mostly clear, but just in these huge globs coming out with and without BM's. Like snot or phlegm out of my A#s

On that note I'm going to bed.
Posted 9/21/2013 4:34 AM (GMT 0)
One last post - or item to look into perhaps:

In Cysytic Fibrosis it's the thickening of the first mucus layer attached or directly above to the epithelial cells that is deadly. The lungs can no longer clear the mucus etc.. In IBD it appears maybe it's the thinning of this layer that causes all the issues: They study CF in mouse intestines - so looking at some of these papers might shed light on how to increase the thickness of the mucus layer or point out some causes of thickneing of mucus. Term: Cystic Fibrosis in mouse intestine model

This particular paper suggests the following: ajpgi.physiology.org/content/291/2/G203

"The effect of MUC1 on mucins and mucus favors a hypothesis that MUC1 is involved in the regulation of mucus amount and mucus formation. This hypothesis is supported by the observed effect of Muc1 on the mucus thickness as studied in live animals. When Muc1 is absent, the firmly adherent mucus layer is significantly thinner. The molecular nature of the loosely and firmly adherent mucus layers is still not known, but the observed effects of an absent Muc1 is well in line with the effects on mucus amounts in both the small and large intestine."

So perhaps we should be looking for things that effect Muc1 - and this I believe all comes right back to threonine as you speak of now trying. I think if I followed it all correctly.

I caught this on wikipedia when I looked up Muc1 - The release of mucins is performed by "sheddases" - Sheddases are membrane-bound enzymes that cleave extracellular portions of transmembrane proteins, releasing the soluble ectodomains from the cell surface. Many sheddases are members of the ADAM or aspartic protease (BACE) protein families. - So maybe looking for something to inhibit these will lead somewhere - or some food additive or toxin that increases these as something to try and eliminate - which probably comes back to the emulsifiers you mention - maybe... i don't know anymore lol.

Confusing stuff.

Now I'm really off to bed.
Posted 9/21/2013 11:10 AM (GMT 0)
Mark: Here is my old thread on goblet cells and whey and threonine from 2012. All the links might not work now.

I don't know if you missed this last night.

The threonine requirement is increased for the synthesis of threonine rich inflammatory proteins at the expense of the mucoprotein synthesis.

So while we are making inflammatory proteins,we are using up the threonine supply and can't make enough

mucus,rather scary,but perhaps part of the solution.  I can see where this one simple statement can really show

how UC might be driven in an unending cycle,unless the threonine supply is quickly increased.

 I wonder what else we are using up that is needed to make mucus.

OM

https://www.healingwell.com/community/default.aspx?f=38&m=2371345

Post Edited (Old Mike) : 9/21/2013 1:54:12 PM (GMT-6)

Posted 9/21/2013 7:15 PM (GMT 0)
OM I made this comment on another post today to InSoFla as I was asking if still taking Threonine nightly - but some thoughts took me down a different path this morning and they resulted in this. Have you been down this road yet?

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

Just Old Mike brought it up last night and I was curious.

I got to thinking about being normal one day, then all of a sudden not normal... And over time the more and more I think about, and read, and listen to others about food intolerance and being all over the map it seems to me that one thing stands out pretty good - an inability to digest certain proteins - not so much carbs, but the proteins in carbs and such.

I stumbled upon an article this morning which states this "All plants produce the enzyme threonine deaminase, or TD1. Howe's research focused on potato and tomato plants, which also have the ability to produce a closely related enzyme TD2 when attacked by caterpillars. Rather than repel caterpillars, however, TD2's devastating effects come later -- in the pests' stomachs. TD2 goes to work in the gut of caterpillars to degrade threonine, a key nutrient they need to grow. In essence, the plant actively starves the caterpillar." - www.sciencedaily.com/releases/2011/03/110329151456.htm

So maybe a deficiency or type of enzymes (or lack thereof) is causing some issues. Not necessarily the enzyme mentioned above, but perhaps something similar that degrades threonine.... causing the need for increased consumption.

Have not thought it through much yet - but have just stumbled on something else related : Meprin (an enzyme involved in the breakdown of protein)
Enzyme involved in inflammatory bowel disease discovered: phys.org/news163159904.html

Post Edited (Canada Mark) : 9/21/2013 1:18:19 PM (GMT-6)

Posted 9/21/2013 7:15 PM (GMT 0)
So what exactly are inflammatory proteins? Does taking threonine exacerbate inflammation then? I remember taking it once, but its hard to get (not available locally). It didnt help much, if at all, so I stopped when I ran out.
Posted 9/21/2013 7:17 PM (GMT 0)
Or perhaps a missing enzyme that without it there's mucus breakdown or something...
Posted 9/21/2013 7:52 PM (GMT 0)
Have not really gone down that road as far as enzymes go.

What I am also finding interesting is that with UC there are a zillion things wrong that they find,mutated genes here,turned off genes over there,

abberant immune response,loss of oral tolerance,dysbiosis.

What the hell is going on,seems like we should all be dead by now,lack of certain enzymes,so many things wrong.

Or is it just the effect of a normal but prolonged immune response,with assocaiated bacterial invasion.

Freddy: Not sure which specific ones they might be referring.

But here is one.

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

http://www.ncbi.nlm.nih.gov/pubmed/20363972

got the threonine from amazon

http://www.amazon.com/Supplement-Direct-L-threonine-Powder-Grams/dp/B006OT5ZWY/ref=sr_1_8?ie=UTF8&qid=1379793668&sr=8-8&keywords=threonine

 

Post Edited (Old Mike) : 9/21/2013 2:01:46 PM (GMT-6)

Posted 9/23/2013 3:03 AM (GMT 0)
Here's something worth a read and perhaps looking into in regards to repairing either the mucus barrier or damaged epithelial cells. I can seem to find out if any clinical trials took place. It's a bit old but intriguing none the less.

articles.baltimoresun.com/1998-02-10/business/1998041007_1_human-genome-sciences-healing-of-wounds-speed-healing

Never thought about it from a "wound" or injury perspective before. Maybe the lining of the colon being like a cut that just can't heal because because of continual onslaught from bacteria type perspective.
Posted 9/23/2013 6:12 PM (GMT 0)
Interesting stuff Mark;

Now I find not only do we have poor mucus quality,but defective colon cell regeneration,oh my.

This is an oldie but goodie, I can only hope that by the time they took the samples from colectomy specimens,

the colon cells were tired/sick and when fed properly they might recover. Will have to look more into

defective regeneration.  If we truly have defective regeneration that just adds to the messx.

Old Mike

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1552771/pdf/gut00707-0043.pdf

TIGAR

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682186/

Notch signaling

http://ajpgi.physiology.org/content/296/1/G23

known today as mucosal healing/regeneration

http://www.jsir.gr.jp/journal/Vol31No3/pdf/06_S2_31.pdf

amino acids heal,arginine pops up but extra arginine seems to make me worse

wish I could find witch ones they used

https://www.ecco-ibd.eu/publications/congress-abstract-s/item/p079-effects-of-a-mixture-of-amino-acids-on-colonic-mucosa-healing-after-experimental-colitis.html

Post Edited (Old Mike) : 9/23/2013 12:42:23 PM (GMT-6)

Posted 9/23/2013 7:04 PM (GMT 0)
www.ncbi.nlm.nih.gov/pmc/articles/PMC3105624/

"If the mucosa heals, it is thought that disease complications are unlikely to occur and future hospitalization and surgery requirements should decrease. If this can be established conclusively, mucosal healing may well become the most important parameter used to assess treatment efficacy because it may best reflect modification of the natural history of the disease as mentioned above."


Worth a read - Looking beyond symptom relief: evolution of mucosal healing in inflammatory bowel disease - Just a paper that discusses the importance of mucosal healing. So anyway we can achieve and repair the mucus being the primary route to sustained remission.


Again I never thought of it from an inability to actually heal the "wound" before. Interesting stuff.

That last paper on amino acids is intriguing.. kind like a tease though without being able to find out what they used.
Posted 9/23/2013 7:10 PM (GMT 0)
HERE YOU GO!

nutrition.highwire.org/content/136/6/1558.full
Posted 9/23/2013 7:12 PM (GMT 0)
remember that guy that went on the meat diet... maybe there is something really to it.
Posted 9/23/2013 7:50 PM (GMT 0)
Don't believe that one is the correct paper, I have posted those before. I have looked and cannot find more,it was a poster paper.

Here is why I don't like arginine,and my gut tells me so.

Also notice from the amino acid mucosal healing paper that the luminal water content was reduced/corrected.

My current stools so far since I have restarted whey,and threonine are stools,not the thin pasty sticky crap that

normally comes out.

Also on meat,I speculated in another thread on diet that, since some people when they switch diet they improve.

My speculation is that each type of preillness diet sets up a specific microbiome, well that is not speculation.

Anyhow,if you are vegan switch to a meat diet,if a meat eater switch to vegan,if omnivore you will have to try both.

Doing this will drastically alter your microbiome,whether it is dysbiotic or not, I suspect.

I also often wonder how/why vegans get UC,well they will tend to be low on threonine, aside pesticides and excess nitrates.

Might even speculate that FT would work better if they looked at the donors diet,in relation to the patient.

Is a omnivore donor good for a vegan patient?????? or vise versa.

The doc's know all this,but perhaps not quite putting it all together,or if they are have not read it.

Here is the thread.

https://www.healingwell.com/community/default.aspx?f=38&m=2858430

Old Mike

arginine gut toxicity/NO

http://jn.nutrition.org/content/137/6/1693S.full

Post Edited (Old Mike) : 9/23/2013 2:24:50 PM (GMT-6)

Posted 9/23/2013 7:52 PM (GMT 0)
So who all is/has been taking threonine?
Posted 9/23/2013 7:58 PM (GMT 0)
Fredy: InSoFl, has been doing threonine and whey for a long time,has a few threads search perfect stools.
It all started when I posted the cheese whey thread,and or the feeding the goblet cells threads about a year ago I believe.  You gotta remember 99.9999999999999999999999999999999999999999999999999999999 %

of the stuff I find does not help people. But that.

0.0000000000000000000000000000000000000000000000000000000000000000000000000000000000001 %

might.

Old Mike

Post Edited (Old Mike) : 9/23/2013 2:10:54 PM (GMT-6)

Posted 9/23/2013 9:05 PM (GMT 0)
From the poster paper thing you posted:/www.ecco-ibd.eu/publications/congress-abstract-s/item/p079-effects-of-a-mixture-of-amino-acids-on-colonic-mucosa-healing-after-experimental-colitis.html

I just noticed the answer to the question of what amino acids they used are:

Theronine, Methionine and Glutamic Acid


Come form the last sentence that I misread as I thought they where Chinese names or something! No offence intended!

"Further work is needed to confirm the effects of Thr, Met and Glu on MH in clinical trials.

No dosage info of course.
Posted 9/23/2013 9:15 PM (GMT 0)
Interesting that methionine can cause brain damage if too much is ingested and yet it is necessary to maintain proper liver function.

http://jn.nutrition.org/content/136/6/1722S.full
[url]
Posted 9/23/2013 9:15 PM (GMT 0)
Good catch Mark: I must be loosing reading comprehension skills in my old age.
Gotta find the fix for this fast. Might be glutamine though as opposed to glutamic acid.
Old Mike

new stuff as I am searching.

here is something I just found,boy do we need our goblet cells

https://www.landesbioscience.com/journals/gutmicrobes/article/23866/

http://www.scielo.br/scielo.php?pid=S0102-86502007000700014&script=sci_arttext

Post Edited (Old Mike) : 9/23/2013 4:14:55 PM (GMT-6)

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