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Rico
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Posted: Sun Nov 2nd, 2008 15:55 |
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Stephen Strauss' (CBC News) latest Vitamin D article (Vitamin D: Not a simple case of cause and effect) mentioning the MP.
A refresher regarding Dr Marshall's science.
And the science according to Dr John White of McGill U (he's mentioned in the article).
Results from Dr Marshall's science:
http://MarshallProtocol.com/MP_results_chart.jpg
http://bacteriality.com/category/interview-patient/
http://www.carouselcharts.com/TranscriptRecoveryLAX2.pdf
http://winmlm.neostrada.pl/mp/townsend/Townsend_Letter_May2007.Part2.pdf
http://tinyurl.com/2pm37t
Results from Dr White's science:
????
Other Strauss Vitamin D articles:
Vitamin D and diabetes: An over-simplified solution to a complex problem
The Vitamin D Debate
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No diagnosis/some symptoms; wife with Sarc on MP; Olm 40mg q6h| avoid D| 1,25D=63 25D=32 (May 2006) 1,25D=44; 25D=10(Dec 2006)PhaseI(May06) PhaseII(Aug06) PhaseIII(Aug07)
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Dr Trevor Marshall
Research Team
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Posted: Sun Nov 2nd, 2008 17:00 |
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Actually, John White's group was responsible for the (very important) exploration of the 913 genes transcribed by the VDR. However, I suspect that project might have been the initiative of his staff member, TT Wang, the lead author, rather than John himself.
http://www.ncbi.nlm.nih.gov/pubmed/16002434
John has never tried to contact me by email or phone, and the (few) phone calls I left on his answering machine during 2006/2007 were not answered.
John was one of the peer reviewers selected to review my Bioessay, and he recommended that it not be published. His peer review failed to declare that he was personally taking 10 times the RDA of Vitamin D, a fact which may have brought his objectivity as a peer reviewer into question
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kenc
Member in Phase 3
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Posted: Mon Nov 3rd, 2008 09:39 |
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The CBC article seems short on details. I'm curious about the nature of the disagreement between Dr. White's view and Dr. Marshall's view.
Reading Dr. White's article in Scientific American I can see he is well aware of the importance of the VDR to immunity. So we have agreement here. Is this just a disaggreement over VDR and agonists and antagonists?Last edited on Mon Nov 3rd, 2008 10:12 by kenc
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Crohn's Disease 1984, 24May05 1,25D=33 25D=8.4, 6Sep05 1,25D=29 25D=12, 11Jun07 25D=<10.4 1,25D=10, 15Sep07 1,25D=14.2 25D=16, 12Jul05 Phase1 + pred, 12Jul06 Phase2 + pred/dexa, 14Aug07 Phase2, prednisone, dexamethasone, testosterone, aspirin, levothyr
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Markt9452
Member in Phase 3
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Posted: Mon Nov 3rd, 2008 10:44 |
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Here is Mr. Whites model from http://www.medicine.mcgill.ca/physio/whitelab/research.htm
I looked at his paper "Vitamin D signaling and regulation of innate immunity" and it's a pretty tough read. One thing I did notice though is that there seems to be lot's of information about mice VDR's used as references.
Last edited on Mon Nov 3rd, 2008 11:39 by Markt9452
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Th1 Lyme Symptoms 125D20 D2510 Ph1Feb08 Ph2Apr08 Ph3Oct08 daily med.exp covered up NoIRs| MyStory|
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kenc
Member in Phase 3
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Posted: Tue Nov 4th, 2008 07:10 |
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Dr. White coauthored this interesting article in Scientific American on vitamin D. It supports Dr. Marshall's emphasis on the importance of the VDR for immunity and describes many of the benefits of VDR activation. However in the latter part of the article it advocates activating the VDR through vitamin D intake (diet and sunshine).
Now I can see why Dr. White would be hostile to Dr. Marshall's work. After contributing this article extolling the virtues of increasing vitamin D intake to a widely circulated magazine, the thought of having to refute his own advice would blind him to the possibility that Dr. Marshall could be right. I expect him to either ignore Dr. Marshall's work or look for evidence to refute it. If it's the latter he may end up having to accept the work or perhaps even become an advocate. Although scientists are supposed to be objective they are still only human. They have egos.
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Crohn's Disease 1984, 24May05 1,25D=33 25D=8.4, 6Sep05 1,25D=29 25D=12, 11Jun07 25D=<10.4 1,25D=10, 15Sep07 1,25D=14.2 25D=16, 12Jul05 Phase1 + pred, 12Jul06 Phase2 + pred/dexa, 14Aug07 Phase2, prednisone, dexamethasone, testosterone, aspirin, levothyr
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Dr Trevor Marshall
Research Team
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Posted: Tue Nov 4th, 2008 17:46 |
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One of the hazards of thinking about the VDR in mice is that it is not found in as many tissues. Hence John's focus on the skin and liver, I think. I found the same error when I was speaking with Ron Evans at Salk, he showed me this huge chart of tissue distribution, and then had to admit it was in a mouse, and then had to admit that macrophages and monocytes traffic all tissues throughout the body. I didn't manage to change Ron's mind though. I suspect John White is the same, and is further in denial because of the palliation he feels when taking 4000 IU a day
Write to Stephen Strauss (by email, not by comments) and let him know your thoughts...
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kenc
Member in Phase 3
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Posted: Wed Nov 5th, 2008 00:30 |
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| I couldn't find Strauss' email address anywhere. Does anyone know what it is?
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Crohn's Disease 1984, 24May05 1,25D=33 25D=8.4, 6Sep05 1,25D=29 25D=12, 11Jun07 25D=<10.4 1,25D=10, 15Sep07 1,25D=14.2 25D=16, 12Jul05 Phase1 + pred, 12Jul06 Phase2 + pred/dexa, 14Aug07 Phase2, prednisone, dexamethasone, testosterone, aspirin, levothyr
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Dr Trevor Marshall
Research Team
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Posted: Wed Nov 5th, 2008 01:32 |
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Ken, look at:
http://www.geocities.com/stephenstrauss@rogers.com/index.html
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edj2001
Moderator
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| Location: | Allen, Texas USA |
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Posted: Wed Nov 5th, 2008 02:56 |
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Paper title: Respiratory Epithelial Cells Convert Inactive Vitamin D to Its Active Form: Potential Effects on Host Defense
http://www.jimmunol.org/cgi/content/abstract/181/10/7090
abstract: "The role of vitamin D in innate immunity is increasingly recognized. Recent work has identified a number of tissues that express the enzyme 1 -hydroxylase and are able to activate vitamin D. This locally produced vitamin D is believed to have important immunomodulatory effects.
In this paper, we show that primary lung epithelial cells express high baseline levels of activating 1-hydroxylase and low levels of inactivating 24-hydroxylase. The result of this enzyme expression is that airway epithelial cells constitutively convert inactive 25-dihydroxyvitamin D3 to the active 1,25-dihydroxyvitamin D3.
Active vitamin D that is generated by lung epithelium leads to increased expression of vitamin D-regulated genes with important innate immune functions. These include the cathelicidin antimicrobial peptide gene and the TLR coreceptor CD14.
dsRNA increases the expression of 1-hydroxylase, augments the production of active vitamin D, and synergizes with vitamin D to increase expression of cathelicidin.
In contrast to induction of the antimicrobial peptide, vitamin D attenuates dsRNA-induced expression of the NF- B-driven gene IL-8.
We conclude that primary epithelial cells generate active vitamin D, which then influences the expression of vitamin D-driven genes that play a major role in host defense. Furthermore, the presence of vitamin D alters induction of antimicrobial peptides and inflammatory cytokines in response to viruses. These observations suggest a novel mechanism by which local conversion of inactive to active vitamin D alters immune function in the lung."
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Sarc98 A.Fib uveitis sk cancer basal/melanoma colon tmr bladder tmr bph| propafenone Armour proscar Guaifensin | 1,25D=50 10/05| 25D=7 4/08| Gene's Story| avd l&D|
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kenc
Member in Phase 3
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Posted: Tue Nov 11th, 2008 08:01 |
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"And it is also fair to say that much of the conventional scientific community thinks Marshall's science — what he personally does is generate computer simulations of how cells and proteins might interact — is somewhere between plain wrong and awfully loony." - Steven Strauss, journalist.
I was very disturbed but not surprised by this sentence in Steven's article on Vitamin D.
I used to believe that if anything significantly new in the scientific community had merrit it would quickly become mainstream. Then I read case after case where the opposite is true; if something is significantly outside the currently accepted model it is fiercely rejected. Here is a short list of famous rejected ideas/inventions. I found the article Strategies for Dissenting Scientists on this site to be especially relevent.
It's surprising to me how little is said about the struggles scientists have had getting their ideas accepted. I've read whole books on Albert Einstein that never mentioned the fact that only one university in Europe accepted the kind of physics he was studying. It was regarded by all the others as quakery. There were times when he was forced to do research in his own apartment.
Sometimes I think the success of a scientist with significanty new ideas is as much to do with his stuggle against his own scientific community as it is with the merrit of his original thoughts.
Last edited on Tue Nov 11th, 2008 08:28 by kenc
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Crohn's Disease 1984, 24May05 1,25D=33 25D=8.4, 6Sep05 1,25D=29 25D=12, 11Jun07 25D=<10.4 1,25D=10, 15Sep07 1,25D=14.2 25D=16, 12Jul05 Phase1 + pred, 12Jul06 Phase2 + pred/dexa, 14Aug07 Phase2, prednisone, dexamethasone, testosterone, aspirin, levothyr
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kenc
Member in Phase 3
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Posted: Tue Nov 11th, 2008 08:41 |
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Here is a link for Brian Martin's Article on Strategies for Disenting Scientists. He's from the University of Wallongong in Australia. What is with the folks from Australia anyway (B. Marshall, T. Marshall, B. Martin and ...)? Is it the relentless sun? 
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Crohn's Disease 1984, 24May05 1,25D=33 25D=8.4, 6Sep05 1,25D=29 25D=12, 11Jun07 25D=<10.4 1,25D=10, 15Sep07 1,25D=14.2 25D=16, 12Jul05 Phase1 + pred, 12Jul06 Phase2 + pred/dexa, 14Aug07 Phase2, prednisone, dexamethasone, testosterone, aspirin, levothyr
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Dr Trevor Marshall
Research Team
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Posted: Tue Nov 11th, 2008 09:28 |
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What is with the folks from Australia anyway? Is it the relentless sun?
All of the above Barry and I both graduated (he MD, I, PhD) in the early 80s from University of Western Australia. There was no concept that Science would not conquer every barrier. Remember that my early studies ended up curing male and female Infertility and curing Cryptorchidism, both with pulsatile hormonal injections. These achievements have vanished into the mists of time because of the inability of Australian Science to understand marketing.
Barry spent many years visiting/studying in the USA, he had a lab here, and I have been here since 1982. When you take the science, and add the marketing know-how you get a killer combination (I hope )
Here is another of those silly senseless pictures which I create with my mathematics. This one was inspired by the paper "A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine."
http://www.ncbi.nlm.nih.gov/pubmed/18505790
CYP3A4 breaks down 1,25-D and you can see it at the bottom of my Bioessay's Fig.1
Here you see Olmesartan docked in the PXR superimposed on a PXR agonist, SR12813. It sure looks like Olmesartan is a likely PXR agonist... Which would help to explain why the 1,25-D levels drops so quickly after Olmesartan is commenced...
I also 'took a picture' of Minocycline docked into the PXR, just like these authors noted, but I was unable to get a satisfactory dock with Clindamycin. I assume that it hits a different receptor (which their wet-biology experiment could not differentiate).
Minocycline acting as a PXR agonist is likely responsible for the palliation achieved with frequently-dosed mino. It is also likely a major component of the initial effectiveness of Mc Pherson Brown's RoadBack protocol...
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Russ
Member in Phase 3
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Posted: Tue Nov 11th, 2008 17:45 |
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Dr Trevor Marshall wrote: Minocycline acting as a PXR agonist is likely responsible for the palliation achieved with frequently-dosed mino.
Is PXR agonism palliative because it lowers 1,25D or is it palliative for some other reason?
If Olmesartan is also a PXR agonist, does that mean that taking it around the clock as we do has the same palliative effect as frequent Mino?
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Lyme, MCS | Phase 1: Jul '06 | Phase 2: Nov '06 | Phase 3: Jul '07
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Bane
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| Joined: | Sun Jan 27th, 2008 |
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Posted: Tue Nov 11th, 2008 18:36 |
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this one is on mice, doesn't it support your claim though? (full text free)
Nuclear xenobiotic receptor PXR locks co-repressor SMRT onto the CYP24A1 promoter to attenuate vitamin D3 activation.
http://www.ncbi.nlm.nih.gov/pubmed/18981260
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Oral Lichen Planus(mild)/Clubbed Finger (digital clubbing)|125D44|18th Feb. 25D14 in phase 2
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Dr Trevor Marshall
Research Team
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Posted: Tue Nov 11th, 2008 19:53 |
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Nuclear xenobiotic receptor PXR locks co-repressor SMRT onto the CYP24A1 promoter to attenuate vitamin D3 activation
Luckily, the PXR is blocked from activation by 1,25-D. I hope that folk are starting to get some idea of the complexity of molecular processes by following this discussion. The body sets up a delicate balance between so many molecules, often an imponderable number of molecules, and if we destroy that balance (with a drug or supplement) we do so at our peril.
Very interesting paper. Still working through it...
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Bane
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Posted: Sat Nov 22nd, 2008 00:51 |
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question: if this paper applies to humans? Does that suggest that olmesartan and Minocycline agonism of the PXR might act as a catalyst on 1.25 degradation as 25D gets below immunesuppressing and 1.25D falls with olmesartan VDR agonism? Your "it's all a matter of dose" comes to mind
Last edited on Sat Nov 22nd, 2008 00:58 by Bane
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Oral Lichen Planus(mild)/Clubbed Finger (digital clubbing)|125D44|18th Feb. 25D14 in phase 2
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findinganswers
Member in Phase 2
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Posted: Mon Nov 24th, 2008 07:24 |
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Dr. Marshall,
So this is old thinking:
"Benicar is a PXR antagonist, but so is 1,25-D (another control loop)." (posted Sun Mar 25th, 2007 22:13) in http://www.marshallprotocol.com/forum39/8264-2.html, right?
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Diabetes type I hypothyroid IBS ADD GAD 125D37 25D12 Ph1Sept07 Ph2Jun08 ModPh2Nov08 25D8.5 (June08) Levoxyl Lantus Humalog Cal/Mag Supp. qod NoIRs lite exp r/t work
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Dr Trevor Marshall
Research Team
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Posted: Mon Nov 24th, 2008 07:45 |
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Nope, that's nearly two years old stuff
Based on a model published more recently I would today opine that Benicar is more likely a PXR agonist at this point, as it is active in the same PXR residues as the known agonist SR12813. The gene SR12813 is confirmed to transcribe is that for CYP3A4.
Minocycline is also a confirmed PXR agonist, at high concentrations. Again for CYP3A4.
1,25-D is still an antagonist
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Lottis
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Posted: Wed Nov 26th, 2008 04:10 |
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Yes, very interesting paper!
The known PXR-target gene Cyp3a11 was induced in both livers and kidney
of all of the PCN-treated Pxr+/+ mice (data not shown).
Neither the basal nor the induced expressions of CYP24A1 mRNA were detected in any of these livers.
In the kidneys, CYP24A1 mRNA was induced in the PCN-treated Pxr+/+ mice only, although the degree of this induction greatly varied.
BMD of whole femoral bones featured a statistically significant decrease after PCN treatment in both Pxr+/+ and Pxr-/- mice |
CYP24 expression only in the kidneys and cyp 3a11 in kidneys and liver...
Given the caveat that vitamin D3 metabolism by mouse CYP3A enzymes
is not known at the present time
and that there may be species differences in how vitamin D3 works,
however, neither hepatic nor intestinal expressions of CYP3A11 mRNA correlated with the PCN-induced loss of the bone mineral density (unpublished observation). |
I just think that since P-gp expression most often go together with the CYP 3A4, and maybe that has something to do with the drug-interaction they are concerned about.
/Lottis
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HTN,LVH,CHF,arrhythmia,hypercholesterol,IBS? fibromyalgia?salivarystones,gallstones,ect...|15feb-07 init. 1,25D 37,5,|25-D 7,8(latest 15/2-07)| Ph1 29/7-08| Palliativ Meds. at the present; |Zoloft|NoIR's|covered up|disabled|
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Dr Trevor Marshall
Research Team
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Posted: Wed Nov 26th, 2008 08:39 |
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Note: The PXR of mice is not a very good analog of the human PXR.
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