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Borrelia burgdorferi reduces VDR expression
 Moderated by: Prof Trevor Marshall Page:  First Page Previous Page  1  2  3  4  5  Next Page Last Page  
 

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Phillyguy
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 Posted: Thu Dec 24th, 2009 07:01

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We now know that the brain controls the formation of bone (12/22/2009)
http://www.physorg.com/news180708867.html

Just plucked this off of Ray Kurzweil's RSS feed. 

"The brain acts as a profound regulatory centre, controlling myriad processes throughout the body in ways we are only just beginning to understand. In new findings, Australian scientists have shown surprising connections between the brain and regulation of bone mass."

This quote struck me as being interesting: 

"It is now clear that the neural network which controls appetite and energy also alters bone density. When we are starving, our brains don't allow us to waste energy by reproducing, making fat or creating new bone. When we are eating too much, on the other hand, our brains make it easier to reproduce, store fat and create bone."

It seems to me that the body downregulates a lot of bodily processes in response to stress, however defined.  Inflammatory cytokines like TNF alpha for example can lead to cachexia (weight loss/wasting), bone loss and other sick behaviours including depressive disorders, etc.

So to me the real question (in the context of this article) is what signalling pathways are involved in the modulation of NPY measured by the researchers?  It doesn't just happen on its own.  TNF aplha, IL-6, IL-1b, AT2?  The reseachers indicate that NPY is modulated in response to stress, presumably infections are part of that equation.

Last edited on Thu Dec 24th, 2009 07:14 by Phillyguy

thelymelight
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 Posted: Thu Dec 24th, 2009 08:12

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Thank-you for your reply and the links to the following papers...I will check them out when I have a moment.:)

I take it when you mention bone matrix, that this includes soft bones...

Yes, she has mentioned once before, that keeping estrogen levels up is important too, but never mentioned it in the context of 'soft bones'....She measures my estrogen yearly and it is just fine, so no peri-menopause for me..:P

I suspect she is on a bit of an EGO trip here (being affiliated with two hospitals and one University) and not use to patients questioning or challenging her...and perhaps she doesn't want to see (via my treatment results down the road) that her beliefs about Vitamin D stores are incorrect or outdated...:shock:



____________________
MP Feb 2008-2015
FM 1990|Lyme,Babs,Bartonella, EBV
Fatigue, shortness of breath, exercise intolerance, temp dysregulation, executive functioning problems,irritable bladder.
Dec'16-25D=28 ng/ml|1,25D =60.42 pg/ml
Apr'14-25D=9.6ng/ml|1,25D =50 pg/mL
thelymelight
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 Posted: Sat Feb 20th, 2010 10:22

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Dr.Marshall perhaps you could speak to this:

I just remembered the other day..that during my childhood whenever I got ill, the Dr.'s never really knew quite what I had...It was like I never got a full blown case of anything.

For Example: They thought I had the measles but weren't 100% sure..same with the mumps I believe...and they thought I might have Scarletina, but didn't know for sure.
Then when I was 18 yrs old, I got this severe flu-like illness, w/alot of dizziness, weakness, fatigue, excessive sleep, nausea, weight loss, light sensitivity, (possibly the start of Lyme disease) and again they didn't know for sure what I had...I was told it was "probably" a virus and that I would slowly recover over time...(which I did) but was never really the same after this episode....

Is this not presenting with full blown sxs (thus Drs' not knowing what I had) a good indication of a poorly functioning immune system (VDR) right from a very young age/perhaps birth?   (Oh, and I was born 2 wks premature)

If so, would that be from inherited bacteria from the mother?

Does this only come from the mother or can it come from the father (via sperm) as well?

I say this b/c my mother is fairly healthy except for some osteoarthritis in her knees..Where as my father has had alot of health problems for many many years now...Heart disease (with a triple by-pass 9 years ago), now the start of Macular Degeneration (which I heard Dr B. say is a Th1 disease), 3 hernia operations, polyps in the colon, prostate cancer a few years ago, gall bladder removed... 

Both he and I are very much a like immune system wise...we are both very sensitive and react to alot of medications, herbs etc..

Your thoughts would be greatly appreciated!:)



____________________
MP Feb 2008-2015
FM 1990|Lyme,Babs,Bartonella, EBV
Fatigue, shortness of breath, exercise intolerance, temp dysregulation, executive functioning problems,irritable bladder.
Dec'16-25D=28 ng/ml|1,25D =60.42 pg/ml
Apr'14-25D=9.6ng/ml|1,25D =50 pg/mL
Prof Trevor Marshall
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 Posted: Sat Feb 20th, 2010 12:40

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http://mpkb.org/doku.php/home:special:pregnancy
 
http://mpkb.org/doku.php/home:publications:marshall_chlamydia2_2009
(slide #27)

Mothers with low Vit D status (and Th1 disease) typically deliver pre-term :)
 

Phillyguy
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 Posted: Fri Jun 18th, 2010 09:00

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CMV downregulates VDR 2.2 Fold

http://www.jimmunol.org/cgi/content/full/181/1/698

Take a look at the data supplement for the full transcriptome: 

http://www.jimmunol.org/cgi/content/full/181/1/698/DC1

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

CMV dramatically increases the expression of inflammatory cytokines.  Per the transcriptome, IL-6 is increased 280 fold!  The TNF family is also significantly upregulated.

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

This little nasty also significantly downregulates TLR1 and TLR6.

The primary known ligand for TLR1 are bacterial triacyl lipopeptides while the primary known ligand for TLR6 are diacyl lipopeptides from mycobacteria.

Most TLR's function as homodimers, however, TLR2 forms heterodimers with TLR1 or TLR6, each dimer having a different ligand specificity.  CMV directly hits TLR1 & 6 and indirectly hits TLR2 via VDR.

TikBitten
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 Posted: Tue Jun 7th, 2011 18:45

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Dr Trevor Marshall wrote: Live Borrelia burgdorferi reduced VDR expression in monocytes by 50 times, and lysates ('dead' Borrelia) reduced it by 8 times (these ratios are not directly comparable with the HIV and TB studies Amy and I cite in our presentations).

So now we can understand the contribution which Borrelia burgdorferi adds to the metagenome...
 

Trevor-
 
Finally dug up this discussion thread that you initiated back on 6/14/09 regarding Bb and VDR suppression, as you can imagine it had caught my attention.  The 50:1 VDR suppression rate, in the presence of live Bb, might account for the level of co-infection I was burdened with when I began the MP March '08.  With that in mind would you please, on a scale of 1-5, rank this statement's merit:

"If HIV (Human Immunedeficiency Virus) suppresses VDR 200:1 then is it not plausible that Borrelia.burgdorferi, at a 50:1 suppression rate, be viewed as a form of Human Immunedeficiency Bacteria, or HIB."
 
Look forward to your most serious thoughts on that comment/observation....


R/TB

Last edited on Tue Jun 7th, 2011 19:51 by TikBitten



____________________
Dx:Neurborreliosis 8/05|25D=46 1,25D=62 10/07|Avoid Sun&VitD since 10/07|Started Ph1&NoIRs 3/08|25D=18 3/08|25D=17 6/08|ModPh2 6/08|Ph2 9/08 stopped NoIRs|Ph3 1/09|25D=13 3/09|25D=10 5/09|25D=11 7/09|25D=15 9/09|25D=9 4/11
Prof Trevor Marshall
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 Posted: Wed Jun 8th, 2011 01:06

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Borrelia does not persist as the complete organism, unlike HIV, they are not comparable.

There is no need to focus on Borrelia. Some of our most seriously ill members have never had a Borrelia infection. It is part of the mix, not a causal factor.

The size of the 50X factor was due to the assay method this study used. There is no reason to suspect there is any major difference in suppression effectiveness between Mycobacterium tuberculosis and Borrelia burgdorferi.

That said, I have long pointed out that HIV profoundly downregulates VDR, but new knowledge is suggesting that it also has a key action on MAF, also called DBP, which the other primary pathogens do not exhibit. So the situation re HIV's virulence is becoming clearer as the years go by.
 
A lot has changed in our scientific understanding  since I started this thread :) Sometimes it is tough to understand the pace of progress. Change it is, but it is also progress.
 

Last edited on Wed Jun 8th, 2011 01:28 by Prof Trevor Marshall

wrotek
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 Posted: Sun Jul 10th, 2011 02:07

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Dr Marshall, if one organism affects VDR in a stronger degree and other organism affects it in lesser degree... Will standard olmesartan dosing work for all these organisms ?

Could there be a pathogen that affects VDR so strongly, that olmesartan won't be able to reverse this process ?



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thelymelight
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 Posted: Sun Jul 10th, 2011 05:18

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Yes good point...What about Babesia? 



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MP Feb 2008-2015
FM 1990|Lyme,Babs,Bartonella, EBV
Fatigue, shortness of breath, exercise intolerance, temp dysregulation, executive functioning problems,irritable bladder.
Dec'16-25D=28 ng/ml|1,25D =60.42 pg/ml
Apr'14-25D=9.6ng/ml|1,25D =50 pg/mL
Prof Trevor Marshall
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 Posted: Sun Jul 10th, 2011 06:16

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Indeed, what about Babesia? What harm does it do? I am not interested in what ILADS says it does, I want to know what harm, and by what pathways...

Babesia survives in weakened immune systems.  The organism is impressive under a microscope, but it lives within red blood cells, and therefore does not significantly affect proteome interference. Easy to see, easy to diagnose, and exaggerated as a pathogen, IMO :) :)
 

Russ
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 Posted: Sun Jul 10th, 2011 11:53

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wrotek wrote: Dr Marshall, if one organism affects VDR in a stronger degree and other organism affects it in lesser degree... Will standard olmesartan dosing work for all these organisms ?

Could there be a pathogen that affects VDR so strongly, that olmesartan won't be able to reverse this process ?

Actually, Borrelia doesn't directly block the VDR like other organisms.  Instead it downregulates it's expression which is a different way of interfering with the immune system and one which Olmesartan does not directly counteract.

In order for the VDR to be "working", the receptor has to be expressed and there needs to be an agonist that binds to it and turns it on.  The way I think of it, a receptor is expressed when it is present in the cell and available for something to bind to it.  It is then turned on when something binds to it and that something is an agonist that turns it on (1,25D, Olmesartan) and not an antagonist that turns it off (25D, bacterial substances). 

Some organisms produce substances that bind to the VDR and block 1,25D from turning it on.  The VDR is still present in the cell, it is still "expressed", but it is not turned on.  Olmesartan, with it's high affinity for the VDR, is able to displace the bacterial substance and turn the VDR on. 

Other organisms - like borrelia, m. tuberculosis, and EBV - prevent the VDR from even being expressed in the first place.  So there is no receptor present for Olmesartan to bind to and therefore Olmesartan does not directly counteract this bacterial survival mechanism.  But I guess the idea is that though borrelia reduces the number of VDRs that are expressed, it does not prevent *all* VDRs from being expressed, so there are still some VDRs out there and by taking Olmesartan you are ensuring that the remaining VDRs re turned on. 

I imagine that in severely infected tissues, borrelia might reduce VDR expression so much that it is very difficult for Olmesartan to work it's magic.  This might be where antibiotics are more necessary, since they would likely interfere with whatever mechanism borrelia uses to prevent VDR expression.  Also, I suspect that carbohydrates/glucose are a key part of the ability of borrelia to do whatever it is that it does, and so eating low-carb would also help and this would explain why some people get much higher IP from lower carb intake.

So I would think that the MP treatment, and especially Olmesartan alone, would be most effective for people with a pathogen mix that leans more towards VDR blockage than one that leans more towards VDR downregulation, since Olmesartan directly counteracts the former but not the latter. 

That is my layman's understanding of it.

Last edited on Sun Jul 10th, 2011 11:56 by Russ



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wrotek
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 Posted: Sun Jul 10th, 2011 12:02

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Interesting. We would have to know how borrelia reduces vdr expression to reverse this .



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Prof Trevor Marshall
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 Posted: Sun Jul 10th, 2011 12:15

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This might be where antibiotics are more necessary, since they would likely interfere with whatever mechanism borrelia uses to prevent VDR expression
We really don't know that bacteriostatic antibiotics directly act on the intracellular organisms. We do know that Mino and Clindy definitely affect the human immune system directly. So the answer is likely even more complex than 'antibiotics', Russ :X

Further, it is believed that VDR is expressed by estrogen-receptor-beta, and in turn the VDR expresses the estrogen receptor precursor protein, so we have a ying-yang feedback/feedforward there.

But you have hit upon the reason I don't talk much about Capnine any more - the complete answer is getting a lot more complex than I contemplated just a  few years ago...
 
 

Last edited on Sun Jul 10th, 2011 12:23 by Prof Trevor Marshall

TikBitten
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 Posted: Sun Jul 10th, 2011 13:35

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Wrotek & Trevor wrote: Dr Marshall, if one organism affects VDR in a stronger degree and other organism affects it in lesser degree... Will standard olmesartan dosing work for all these organisms? Could there be a pathogen that affects VDR so strongly, that olmesartan won't be able to reverse this process?
Further, it is believed that VDR is expressed by estrogen-receptor-beta, and in turn the VDR expresses the estrogen receptor precursor protein, so we have a ying-yang feedback/feedforward there. 
Wrotek & Trevor-

IMO, I believe there are two primary levels of concern, at a minimum, in addressing microbacterial persistence:  

 i. The first, of course, as stated above, pathogenic effect on VDR expression but, also;

ii. Each pathogen's inherent ability (genetic makeup) for biofilm persistence, cyst formation, sequestering and immune system evasion. 

Case in point, me....

After three plus years on the MP I am far more comfortable discussing the topic as it appears this is the exact diagnostic scenario that’s unfolding in my treatment of Late Stage Lyme Disease, the result of an underlying long standing Borreliosis (Bb) condition.  Just as a comparison, much like AIDS is the disease state of HIV, Lyme Disease is the disease state caused by Borreliosis. 

As way of some background, the major concern when embarking on the MP was that, although the MP had the potential of clearing much of the micro-bacterial and other pathogenic load, in the end, a Borrelia infection would be far too resilient to roll back entirely.  And, unfortunately, at this point in time, my test results indicate just that scenario.

When I started on the MP in March 2008 it was difficult to know, due to a plethora of positive fungal/viral/bacterial test readings, if Lyme Disease was in fact the primary diagnosis.  By April of 2010, however, the underlying “pea-soup” condition became far clearer and the only detectable IGenex western blot signature left, kdA bands 31 & 41, was that of Borrelia.  Again, the causative agent underlying Lyme Disease.  Please know that when only those two bands are present (31 & 41) the likelihood of a positive Borreliosis diagnosis (Specificity & Sensitivity) reaches a 97% confidence level -- and additionally confirmed as positive with further 31 kDa epitope Igenex testing.

To make matters worse, as another confirmation, I recently performed a new, more comprehensive test panel from NeuroSciences Labs, Inc. that scanned not only western blot bands but also looked for key markers of Bb biofilm formation.  So as of March 23rd 2011, my results remain weakly positive for kDa bands 31 & 41 but, more alarmingly, a key marker (DbpA) for Bb extracellular matrix binding (i.e. biofilm formation) was identified and off the scale.  Thus leading my physician to believe that, although the MP was likely successful at clearing out much of the pathogenic pea-soup, much work is still needed to fully address the in-vivo biofilm life cycle of Bb.   

While I have surely improved greatly from 2008, at this point in time, the underlying causative pathogen, Bb, is proving to be very, very resilient.  At present I am working with my physician to develop additional layers of therapy, come December, that will compatibly overlay the MP and breakdown or interfere with ongoing Bb biofilm formation.

So net, net, in contrast to Dr. Marshall’s beliefs, I am definitely not of the opinion all bacteria are created equal and, hence, evenly susceptible in-vivo to the MP – at least not yet!!JJ

My 2 Cents,
TB

Last edited on Sun Jul 10th, 2011 13:42 by TikBitten



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Dx:Neurborreliosis 8/05|25D=46 1,25D=62 10/07|Avoid Sun&VitD since 10/07|Started Ph1&NoIRs 3/08|25D=18 3/08|25D=17 6/08|ModPh2 6/08|Ph2 9/08 stopped NoIRs|Ph3 1/09|25D=13 3/09|25D=10 5/09|25D=11 7/09|25D=15 9/09|25D=9 4/11
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 Posted: Sun Jul 10th, 2011 13:55

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a new, more comprehensive test panel from NeuroSciences Labs, Inc. that scanned not only western blot bands but also looked for key markers of Bb biofilm formation
Is that an FDA-approved test, or are you placing your fate in the hands of pseudo-science, TB? :) :) :)
 

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 Posted: Sun Jul 10th, 2011 14:28

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Dr Trevor Marshall wrote:
"We do know that Mino and Clindy definitely affect the human immune system directly".
What exactly do we know about Clindy in that respect ? Quite a bit of info on Mino has been posted (Bane, Phillyguy), but Clindy ??? Nil specific in the MPKB either.
Thx, Leo.

wrotek
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 Posted: Sun Jul 10th, 2011 15:01

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This is off topic(I dont want to start new thread), but perhaps it could be possible to clone a conference countdown timer to http://marshallprotocol.com and mpkb.org websites ?
I have just realized that i missed 3 conferences and tomorrow i have 3 hours to catch up :D

Last edited on Sun Jul 10th, 2011 21:44 by wrotek



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Prof Trevor Marshall
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 Posted: Sun Jul 10th, 2011 15:10

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My response was a bit terse TB. Sorry about that. I get very upset over the way that the"Lyme" industry drains every penny from members by convincing them they have "Lyme" and then coming up with bogus test after bogus test until both the patients, and their families, have been bankrupted.

The new test you mentioned has (at least) the following flaws:
Firstly, it is based on antibodies which have not been demonstrated to be specific for Borrelia, with a real risk of false-positive against other components of the microbiota. If you watch Amy's presentation at the Intl Congress on Antibodies:

http://www.youtube.com/watch?v=SGe9UTQJdHM

you will hear her explain how useless the average 'antibody' is, as they are non-specific, and hit hundreds of targets. None of the experts in the audience challenged this. Another paradigm shift for clinical medicine to leap, I am afraid :X

Second, biofilms are not what are making you ill. If you have any Borrelia in your bloodstream it is because of the combined load of all the intra-phagocytic  pathogens weakening your immune system, thereby allowing "cysts" and whatever, to persist in the blood and tissues. The concept of "Borrelia cysts" in-live- Homo-sapiens is junk science anyway, for a host of other reasons which I have enumerated over the last decade.

While you have any immune system at all, it will deal with blood-borne flotsam and jetsam. If your immune system is too weak to do this you will die because of the accumulating apoptotic cells, quite apart from any pathogenic issues.

I hope that helps.

IMO it is always best to ask before spending money on what the Lyme-financial-ecosystem is pushing at you :)
 
 

Last edited on Sun Jul 10th, 2011 16:05 by Prof Trevor Marshall

Prof Trevor Marshall
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 Posted: Sun Jul 10th, 2011 15:15

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Leo,
Clindy has been reported as a CYP3A4 enhancer, and it was reported that this was achieved via the PXR.

http://www.ncbi.nlm.nih.gov/pubmed/18505790

Although I did confirm (in-silico) the PXR activity of mino, I was unable to confirm that clindy was a PXR agonist, and so there is a question in my mind about the pathway, but I will accept the researcher's observations that clindy enhanced the expression of CYP3A4, which, among other things, breaks down 1,25-D into inactive metabolites :)
 

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 Posted: Mon Jul 11th, 2011 01:05

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TikBitten, I think Dr. Marshall is right about antibody tests being non-specific and not a good marker of the level of infection.  I had a bunch of blood work done shortly after starting the MP and all sorts of antibody tests that had been negative prior to the MP were now positive because my immune system was working and killing pathogens.

As far as your main point about whether the MP alone will allow recovery in all cases, regardless of severity of disease and pathogen mix, I have wondered the same thing.  It's hard to think that it would, given the infinite number of pathogen combinations and ways in which the pathogens affect the body.  I guess only time will tell. 

And I also think that biofilms play a role.  Or at least some mechanism in which they are able to go into "hiding" when the environment is not right. 

Last edited on Mon Jul 11th, 2011 01:15 by Russ



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