Paging Tex - re mast cells
Moderators: Rosie, Stanz, Jean, CAMary, moremuscle, JFR, Dee, xet, Peggy, Matthew, Gabes-Apg, grannyh, Gloria, Mars, starfire, Polly, Joefnh
Hi Gabes, In your post you stated that you be taking more zinc. The only problem with high levels of zinc over an extended period is that it will lower your copper. The ratio of these two trace elements are important. I am taking copper twice a day to correct my ratio. This may change when I have the next hair analysis. The max copper per day for a male is 2mgs. Jon
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Gabes-Apg
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I have only ever used oral liquid, it is practitioner only type of zinc liquid
(ie you can't buy it online or over the counter per say)
For the past 4 years, any dental issues, and more often before and after any dental work, I brush my teeth and gums with it.
If I am having cold /flu symptoms I up the Vit d3 and the zinc.
regardless of the delivery method, a key part getting the test results and understanding MTHFR and /or Pyrrole is that the correct biochemical process for these items is not occurring.
I may well be be taking the right things in the optimum delivery method, but they are not being processed in my body properly.
Pyroluria is a Blood Disorder
When the body creates hemoglobin there is a byproduct called kryptopyrroles. The kryptopyrroles in Pyroluria sufferers multiply too fast and block receptor sites for B-6 and zinc. This creates a serious deficiency of these two nutrients.
(ie you can't buy it online or over the counter per say)
For the past 4 years, any dental issues, and more often before and after any dental work, I brush my teeth and gums with it.
If I am having cold /flu symptoms I up the Vit d3 and the zinc.
regardless of the delivery method, a key part getting the test results and understanding MTHFR and /or Pyrrole is that the correct biochemical process for these items is not occurring.
I may well be be taking the right things in the optimum delivery method, but they are not being processed in my body properly.
Put most simply, MTHFR converts 5,10-methylenetetrahydrofolate into the activated form, 5-MTHF or 5-methyltetrahydrofolate. Though this reaction plays a part in many biochemical pathways, it is probably best-known in the context of breaking down the amino acid homocysteine. This process produces methionine and eventually S-Adenosylmethionine (SAMe), a crucial DNA methylator.
Other significant roles of a properly functioning MTHFR enzyme include nucleic acid biosynthesis, neurotransmitter synthesis, and production of signaling molecules important for regulating embryonic development, all of which will be discussed in more detail in later sections.
Pyroluria is a Blood Disorder
When the body creates hemoglobin there is a byproduct called kryptopyrroles. The kryptopyrroles in Pyroluria sufferers multiply too fast and block receptor sites for B-6 and zinc. This creates a serious deficiency of these two nutrients.
Gabes Ryan
"Anything that contradicts experience and logic should be abandoned"
Dalai Lama
"Anything that contradicts experience and logic should be abandoned"
Dalai Lama
Hi Tex,
I found this reference: http://mpkb.org/home/pathogenesis/vitamind/metabolism
It talks about bacteria "disabling" or down regulating the VDRs. And look at two of the bacteria species known to do this - Mycobacteria! You and I have always been suspicious of mycobacterium (M. paratuberculosis especially).
Bacteria and the VDR
The Antimicrobial Peptide Database lists hundreds of antimicrobial peptides known to kill or inhibit the reproduction of bacteria,11 793 AmPs found in animals as of January 5, 2009. The sheer diversity of these proteins coupled with the fact that they have been conserved over millenia suggests that enough pathogenic bacteria exist in sufficient quantities to warrant the evolution of these defense mechanisms. It would seem that is in the strong interest of the human body to destroy or disrupt these bacteria.
Pathogenic bacteria are likewise driven by evolutionary impetus: it's in their interest to disrupt the proteins, which interfere with their growth. In what way or ways could bacteria interrupt production of the AmPs?
According to one researcher, it is nearly impossible for bacteria to develop resistance to the AmPs:
"Acquisition of resistance by a sensitive microbial strain against antimicrobial peptides is surprisingly improbable". (Michael Zasloff)
However, what if it were possible to disrupt the expression of the Vitamin D Receptor by secreting ligands, which bind to and inactivate the receptor? Such bacteria would have an undeniable reproductive advantage.
"Think about this for a minute – if you were a persistent pathogen, wouldn’t it seem a good idea to disable your host’s ability to produce antimicrobial peptides? And if you discovered that disabling just one receptor, the VDR, would get rid of both cathelicidin and defB2, wouldn’t you try to evolve a mechanism for doing that"? (Trevor Marshall, PhD)
Bacteria disable the VDR
Capnine is a protein created by bacteria, a protein which may bind to and antagonize (inactivate) the VDR. The secretion of capnine and substances like it fulfills an important evolutionary need for bacteria: to disrupt the innate immune response.
In the arms race of host–microbe co-evolution, successful microbial pathogens have evolved ingenious ways to evade host immune responses.
"Studies have indicated that the dysregulation of VDR may lead to exaggerated inflammatory responses, raising the possibility that defects in Vitamin D and VDR signaling transduction may be linked to bacterial infection and chronic inflammation. Further characterization of Vitamin D/VDR will help elucidate the pathogenesis of various human diseases and in the design of new approaches for prevention and treatment". (Jun Sun)
Since the VDR is at the heart of the innate immune system, bacteria can survive by discovering how to disable it through a variety of different actions. Actions accumulate and are more powerful than individual actions.
In keeping with evolutionary theory, a growing number of substances and species have been shown to downregulate the activity of the VDR:
Borrelia burgdorferi – Live Borrelia burgdorferi reduced VDR expression in monocytes (phagocytes) by 50 times, and lysates (“dead” Borrelia) reduced it by 8 times15
Mycobacterium tuberculosis – shown to downregulate the VDR 3.3-fold 16 which makes sense given that an active VDR helps phagocytes to suppress the intracellular growth of M. tuberculosis 17 18
Mycobacterium leprase – produces microRNA-21 to target multiple genes associated with the VDR19
“Gliding” biofilm bacteria have been shown to create Capnine – Capnine is a 2-amino-3-hydroxy-15-methylhexadecane-1-sulfonic acid, and is created by the genera Cytophaga, Capnocytophaga, Sporocytophaga, and Flexibacter.20 21 The secretion of capnine meets an important evolutionary need for bacteria. Capnine possesses a high affinity for the VDR as evidenced by the fact that molecular modeling shows that its stable in the ligand binding pocket. Molecular modeling further shows that when capnine is docked in the VDR, it inactivates the receptor.
Chlamydia trachomatis – shown to downregulate the VDR in unpublished work
The following substances reduce the number of VDR, without which immune function is limited:
Caspase-3 – A protein which cleaves (breaks apart) the VDR structure and thus limits the ability of VDR to perform gene transcription.22 The caspases are upregulated by Shigella infection,23 which implies that the VDR may have a faster cycle time in disease than in health.
According to the Marshall Pathogenesis, pathogens' production of ligands, which bind to and antagonize (inactivate) the Vitamin D Receptor, is one of the fundamental processes by which chronic inflammatory disease occurs. The consumption of other immunosuppressive substances also has an effect.
Studies have shown that at least several pathogens downregulate VDR expression.
One promising area for future research is to fully characterize the breadth and diversity of proteins created by bacteria in infected cells.
Love,
Polly, who loves being compared to a warm rain on a spring day!
I found this reference: http://mpkb.org/home/pathogenesis/vitamind/metabolism
It talks about bacteria "disabling" or down regulating the VDRs. And look at two of the bacteria species known to do this - Mycobacteria! You and I have always been suspicious of mycobacterium (M. paratuberculosis especially).
Bacteria and the VDR
The Antimicrobial Peptide Database lists hundreds of antimicrobial peptides known to kill or inhibit the reproduction of bacteria,11 793 AmPs found in animals as of January 5, 2009. The sheer diversity of these proteins coupled with the fact that they have been conserved over millenia suggests that enough pathogenic bacteria exist in sufficient quantities to warrant the evolution of these defense mechanisms. It would seem that is in the strong interest of the human body to destroy or disrupt these bacteria.
Pathogenic bacteria are likewise driven by evolutionary impetus: it's in their interest to disrupt the proteins, which interfere with their growth. In what way or ways could bacteria interrupt production of the AmPs?
According to one researcher, it is nearly impossible for bacteria to develop resistance to the AmPs:
"Acquisition of resistance by a sensitive microbial strain against antimicrobial peptides is surprisingly improbable". (Michael Zasloff)
However, what if it were possible to disrupt the expression of the Vitamin D Receptor by secreting ligands, which bind to and inactivate the receptor? Such bacteria would have an undeniable reproductive advantage.
"Think about this for a minute – if you were a persistent pathogen, wouldn’t it seem a good idea to disable your host’s ability to produce antimicrobial peptides? And if you discovered that disabling just one receptor, the VDR, would get rid of both cathelicidin and defB2, wouldn’t you try to evolve a mechanism for doing that"? (Trevor Marshall, PhD)
Bacteria disable the VDR
Capnine is a protein created by bacteria, a protein which may bind to and antagonize (inactivate) the VDR. The secretion of capnine and substances like it fulfills an important evolutionary need for bacteria: to disrupt the innate immune response.
In the arms race of host–microbe co-evolution, successful microbial pathogens have evolved ingenious ways to evade host immune responses.
"Studies have indicated that the dysregulation of VDR may lead to exaggerated inflammatory responses, raising the possibility that defects in Vitamin D and VDR signaling transduction may be linked to bacterial infection and chronic inflammation. Further characterization of Vitamin D/VDR will help elucidate the pathogenesis of various human diseases and in the design of new approaches for prevention and treatment". (Jun Sun)
Since the VDR is at the heart of the innate immune system, bacteria can survive by discovering how to disable it through a variety of different actions. Actions accumulate and are more powerful than individual actions.
In keeping with evolutionary theory, a growing number of substances and species have been shown to downregulate the activity of the VDR:
Borrelia burgdorferi – Live Borrelia burgdorferi reduced VDR expression in monocytes (phagocytes) by 50 times, and lysates (“dead” Borrelia) reduced it by 8 times15
Mycobacterium tuberculosis – shown to downregulate the VDR 3.3-fold 16 which makes sense given that an active VDR helps phagocytes to suppress the intracellular growth of M. tuberculosis 17 18
Mycobacterium leprase – produces microRNA-21 to target multiple genes associated with the VDR19
“Gliding” biofilm bacteria have been shown to create Capnine – Capnine is a 2-amino-3-hydroxy-15-methylhexadecane-1-sulfonic acid, and is created by the genera Cytophaga, Capnocytophaga, Sporocytophaga, and Flexibacter.20 21 The secretion of capnine meets an important evolutionary need for bacteria. Capnine possesses a high affinity for the VDR as evidenced by the fact that molecular modeling shows that its stable in the ligand binding pocket. Molecular modeling further shows that when capnine is docked in the VDR, it inactivates the receptor.
Chlamydia trachomatis – shown to downregulate the VDR in unpublished work
The following substances reduce the number of VDR, without which immune function is limited:
Caspase-3 – A protein which cleaves (breaks apart) the VDR structure and thus limits the ability of VDR to perform gene transcription.22 The caspases are upregulated by Shigella infection,23 which implies that the VDR may have a faster cycle time in disease than in health.
According to the Marshall Pathogenesis, pathogens' production of ligands, which bind to and antagonize (inactivate) the Vitamin D Receptor, is one of the fundamental processes by which chronic inflammatory disease occurs. The consumption of other immunosuppressive substances also has an effect.
Studies have shown that at least several pathogens downregulate VDR expression.
One promising area for future research is to fully characterize the breadth and diversity of proteins created by bacteria in infected cells.
Love,
Polly, who loves being compared to a warm rain on a spring day!
Blessed are they who can laugh at themselves, for they shall never cease to be amused.
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Gabes-Apg
- Emperor Penguin
- Posts: 8332
- Joined: Mon Dec 21, 2009 3:12 pm
- Location: Hunter Valley NSW Australia
It talks about bacteria "disabling" or down regulating the VDRs. And look at one of the bacteria known to do this - Mycobacterium tuberculosis! You and I have always been suspicious of mycobacterium (M. paratuberculosis especially).
ika curumba! now we are getting into the layers of WHY!The consumption of other immunosuppressive substances also has an effect.
thanks Polly and Tex for this discussion and spending the time researching...
Gabes Ryan
"Anything that contradicts experience and logic should be abandoned"
Dalai Lama
"Anything that contradicts experience and logic should be abandoned"
Dalai Lama
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Sheila
- Rockhopper Penguin
- Posts: 1150
- Joined: Wed May 18, 2011 5:10 am
- Location: Palm Beach Gardens, Fl
I was pretty ignorant about the relationship between Mast Cells and MC. This discussion made be begin searching online for information and an explanation I can understand. I found an article at www.allergycliniconline.com written by an Indonesian pediatrician.
He believes acute and chronic stress is a cause of aberrant proliferation of tissue mast cells. He also mentioned that mast cell etiology shows up as thickened collagen bands, excessive eosinophils/lymphocytes etc.
Mast cells were measured in the upper part of the lamina propria in patients with collagenous colitis, Crohn's and ulcerative colitis. The number of mast cells was higher than normal when compared to normal controls. When mast cells were measured in other parts of the colon, those with CC had normal mast cells while higher in Crohn's and UC.
The different distribution of mast cells and macrophages in CC and inflammatory bowel disease and this suggests that because mucosal mast cells have been implicated in the development of Th2 response. Collagenous colitis is more of a Th2 type reaction than T1.
It is an interesting article and helped me understand better what this discussion is about. The author also said gastritis is caused by mast cells, including cases with and without the presence of h. Pylori. I just did the test for h. Pylori for gastritis pain. I doubt that I have an ulcer. Could gastritis be caused by mast cell proliferation?
Sheila W.
He believes acute and chronic stress is a cause of aberrant proliferation of tissue mast cells. He also mentioned that mast cell etiology shows up as thickened collagen bands, excessive eosinophils/lymphocytes etc.
Mast cells were measured in the upper part of the lamina propria in patients with collagenous colitis, Crohn's and ulcerative colitis. The number of mast cells was higher than normal when compared to normal controls. When mast cells were measured in other parts of the colon, those with CC had normal mast cells while higher in Crohn's and UC.
The different distribution of mast cells and macrophages in CC and inflammatory bowel disease and this suggests that because mucosal mast cells have been implicated in the development of Th2 response. Collagenous colitis is more of a Th2 type reaction than T1.
It is an interesting article and helped me understand better what this discussion is about. The author also said gastritis is caused by mast cells, including cases with and without the presence of h. Pylori. I just did the test for h. Pylori for gastritis pain. I doubt that I have an ulcer. Could gastritis be caused by mast cell proliferation?
Sheila W.
To get something you never had, you have to do something you never did.
A person who never made a mistake never tried something new. Einstein
A person who never made a mistake never tried something new. Einstein
Hi Polly,
Sorry I've been absent for a while (I'll be a happy camper when I finally finish my tax return).
Well, I think you've done it. That's it — the missing link. That's an awesome article, and it definitely adds a lot of insight and illumination to the topic at hand.
I'll have to analyze this some more over the weekend. It's late enough now, that my brain keeps slipping into neutral.
But there's enough information in this thread now, to keep the gears in all of our brains happily turning for quite a while.
Great find!
Love,
Tex
Sorry I've been absent for a while (I'll be a happy camper when I finally finish my tax return).
Well, I think you've done it. That's it — the missing link. That's an awesome article, and it definitely adds a lot of insight and illumination to the topic at hand.
I'll have to analyze this some more over the weekend. It's late enough now, that my brain keeps slipping into neutral.
But there's enough information in this thread now, to keep the gears in all of our brains happily turning for quite a while.
Great find!
Love,
Tex
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.
I don't see any reason why it couldn't. And I would assume that it could also be caused by a reduced expression of vitamin D receptors (IOW, suppression of vitamin D receptors). Maybe H. pylori have the ability to do that.Sheila wrote:Could gastritis be caused by mast cell proliferation?
Tex
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.
Tex,
This article is totally in synch with your views about bacteria - how incredibly ingenious and determined they are to overcome our defenses. (Proof that a brain isn't needed to survive and prosper on this planet. LOL!).
I wonder if, increasingly, bacteria are developing ligands (and probably many other similar substances) as a way to fight back at us for our overwhelming use of antibiotics. And how clever of them not to limit their efforts to developing resistance only to selected exogenous antibiotics, but to disrupt a major innate (endogenous) immune mechanism throughout the body (the VDR). We know that vitamin D is so important because it actually works like a hormone and not a vitamin and that its receptors are EVERYWHERE in the body. If the VDR system is the key to auto-immunity, then perhaps much of the blame for the huge increase in AI diseases is due to bacteria's ability to dismantle it.
OK, shall we become lab partners and try to develop anti-ligand treatments? Of course, they wouldn't work for long, because the bacteria would soon develop new ones. Devious little critters, ain't they?
Love,
Polly
P.S. At least you have only 3 more days to fool with taxes (unless you are filing for an extension). Good luck.
This article is totally in synch with your views about bacteria - how incredibly ingenious and determined they are to overcome our defenses. (Proof that a brain isn't needed to survive and prosper on this planet. LOL!).
I wonder if, increasingly, bacteria are developing ligands (and probably many other similar substances) as a way to fight back at us for our overwhelming use of antibiotics. And how clever of them not to limit their efforts to developing resistance only to selected exogenous antibiotics, but to disrupt a major innate (endogenous) immune mechanism throughout the body (the VDR). We know that vitamin D is so important because it actually works like a hormone and not a vitamin and that its receptors are EVERYWHERE in the body. If the VDR system is the key to auto-immunity, then perhaps much of the blame for the huge increase in AI diseases is due to bacteria's ability to dismantle it.
OK, shall we become lab partners and try to develop anti-ligand treatments? Of course, they wouldn't work for long, because the bacteria would soon develop new ones. Devious little critters, ain't they?
Love,
Polly
P.S. At least you have only 3 more days to fool with taxes (unless you are filing for an extension). Good luck.
Blessed are they who can laugh at themselves, for they shall never cease to be amused.
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wmonique2
- Rockhopper Penguin
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Paging Tex---mast cells
Polly,
Before I made the plunge to LDN I researched it for a long time...I can't recall where and I don't have a link but somewhere I read that LDN not only affects H1 and H2 but also H3 and H4. I had never heard of H3 and H4 prior...Now that I am taking it, it makes sense to me.
Monique
Before I made the plunge to LDN I researched it for a long time...I can't recall where and I don't have a link but somewhere I read that LDN not only affects H1 and H2 but also H3 and H4. I had never heard of H3 and H4 prior...Now that I am taking it, it makes sense to me.
Monique
Diagnosed 2011 with LC. Currently on Low Dose Naltrexone (LDN)
Hi Polly, Thank you for the post. The researchers for FSHD explain that there is "suppression of the innate immune". This helps with the sequence of events for the why I have both FSHD and MC. I will explain the sequence in a future post after I go through the research reports on file. I always suspected a bacteria or a virus. One blood test I will insist my PCP order will be a Lyme disease test since a member of my family with FSHD tested positive for Lyme disease. Jon
Bon jour, Monique!
That's very interesting. So happy to hear about your improvement!
Hi Gluten,
You are welcome! Yes, you are absolutely correct. This theory explains why other autoimmune diseases are so common in MCers.
BTW, Tex and I have always suspected an underlying infectious process, too!
I will look forward to your next post.
Polly
That's very interesting. So happy to hear about your improvement!
Hi Gluten,
You are welcome! Yes, you are absolutely correct. This theory explains why other autoimmune diseases are so common in MCers.
BTW, Tex and I have always suspected an underlying infectious process, too!
I will look forward to your next post.
Polly
Blessed are they who can laugh at themselves, for they shall never cease to be amused.
FWIW, the suppression of the availability of VDRs by bactera-produced ligands apparently is the primary mode by which the innate immune system is suppressed, and this allows the development of autoimmune-type syndromes to proceed. IOW, in order to function normally, the innate immune system requires activation of the available vitamin D receptors (by vitamin D).Jon wrote:The researchers for FSHD explain that there is "suppression of the innate immune".
But that can't happen if the ligands produced by bacteria beat the vitamin D to the receptors, and bind there first. This is the same way that antihistamines work, for example, by binding to the histamine receptors before the histamine can bind to them. From the article that Polly cited:
The innate immune response is the body's first line of defense against and non-specific way for responding to bacterial pathogens.2 Located in the nucleus of a variety of cells, the Vitamin D nuclear receptor (VDR) plays a crucial, often under-appreciated, role in the innate immune response.
When functioning properly, the VDR transcribes between hundreds3 and thousands of genes4 including those for the proteins known as the antimicrobial peptides. Antimicrobial peptides are “the body's natural antibiotics,” crucial for both prevention and clearance of infection.5 The VDR also expresses the TLR2 receptor, which is expressed on the surface of certain cells and recognizes foreign substances.
The body controls activity of the VDR through regulation of the vitamin D metabolites. 25-hydroxyvitamin D (25-D) antagonizes or inactivates the Receptor while 1,25-dihydroxyvitamin D (1,25-D) agonizes or activates the Receptor.
Tex
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.