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Dr Trevor Marshall
Research Team
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Posted: Fri Apr 3rd, 2009 14:14 |
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One of the proteins heavily down-regulated by the VDR is Endothelin-1, a very strong vasoconstrictor (Wikipedia has some info on endothelins)
Endothelin-1 also has profound effects on the brain, possible mediating seizures (in a rat model):
http://www.ncbi.nlm.nih.gov/pubmed/7509966
So there is a hot lead for you to chase down  I am focusing on the Prague conference presentations right now, and too busy to explore this much further
I wonder if this is our link to the orthostatic hypotension that afflicts nearly everybody during early stages of recovery ??
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Lottis
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Posted: Sun Apr 5th, 2009 21:22 |
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Very interesting.
| Widely distributed in the body, receptors for endothelin are present in blood vessels and cells of the brain, choroid plexus and peripheral nerves. When applied directly to the brain of rats in picomolar quantities as an experimental model of stroke, endothelin-1 caused severe metabolic stimulation and seizures with substantial decreases in blood flow to the same brain regions, both effects mediated by calcium channels.[5] |
I have been thinking about the cause of endocarditis for a few months, and the picture is getting clearer now. Personally I have never been able to tolerate CCB's since I have a lot more arrythmias from them all. One period I had both CCB and carvedilol together, and that was quite bad for the conducting in the heart.
I had an strong positive effect from changing to the alfa-beta blocker carvedilol. The alfa blocker has improved my angina by the relaxation of the endothel lining of the arteries.
Headache lately has also been worse, maybe from finally getting more blood into my brain...
I will dig more into this. Thank you very much!
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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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Rajabesar
Health Professional
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Posted: Wed Apr 8th, 2009 06:38 |
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Thanks for the heads-up on that.
I am using BP as a monitoring tool for efficacy of treatment in my MP patients. Best tool I have found yet. Nice to see a possible mechanism.
The puzzle pieces just keep tumbling into place.
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Experience is what you get right after you needed it.
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stuckpac
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Posted: Wed Apr 8th, 2009 16:03 |
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Rajabesar,
Would that be (BP) Back Pain or Blood Pressure as your efficacy monitory tool? Sorry, we use BP as acronyms for both where I work
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Rajabesar
Health Professional
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Posted: Wed Apr 8th, 2009 22:11 |
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BP as in blood pressure.
We use LBP for the usual back pain. BP for blood pressure. HTN or HBP for hypertension. Must be a regional thing. We do a lot of strange things in Alaska
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stuckpac
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Posted: Wed Apr 8th, 2009 23:58 |
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| So how do you use it as a monitoring tool? Is it if the blood pressure is well-controlled or low, you see a relationship between that and whether the patient is having expected IP reactions? Or what exactly is it you see? Thanks for any explanation you might have.
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Rajabesar
Health Professional
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Posted: Thu Apr 9th, 2009 05:11 |
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Yes, the lower the BP the better the response to the antibiotics (IP reaction). The BP reduction seems unrelated to the Olmesartan dosage or timing but strongly related to antibiotics. I have begun using the hypotensive or normotensive state as a gauge useful in ramping the antibiotics. I have seen systolics as low as 60 in some patients when adding or increasing antibiotic dosages. A bit scary at first but everyone seems to do well in the long run.
"Off diet" with increased D ingestion also seems to bring back more normal BP.
Those that have taken a break from the antibiotics and stayed on the Olmesartan return to normal blood pressures and when resuming the antibiotics will become hypotensive again. It typically takes a while for the low BP response to re-occur.
Another useful tool is fatigue. Pretty profound in some but not as objective and more difficult to quantify but clearly parallel to the low BP
I have also noticed increases in creatinine and decrease in creatinine clearance that seems to parallel both fatigue and low BP. Whether due to renal hypo-perfusion or some other mechanism I am not quite clear on. Could use some input on that phenomenon.
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stuckpac
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Posted: Thu Apr 9th, 2009 14:36 |
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| Thank you for taking the time to reply. It seems to make sense. I wonder if any other health care professionals have noted these findings. As they say in the business, time for another study!
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Dr Trevor Marshall
Research Team
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Posted: Thu Apr 9th, 2009 14:56 |
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I have also noticed increases in creatinine and decrease in creatinine clearance that seems to parallel both fatigue and low BP. Whether due to renal hypo-perfusion or some other mechanism I am not quite clear on. Could use some input on that phenomenon
The production of renin and the angiotensinogens is controlled by the VDR nuclear receptor, and therefore directly related too the immunopathology. I explained this in some detail, with reference to a recent paper on the subject, in my Seminar at West China Hospital.
The video of the seminar is at:
http://www.vimeo.com/2599416
and a transcript is available at
http://AutoimmunityResearch.org/transcripts/WCH_2008_seminar_transcript.pdf
The reversibility of the GFR and creatinine mechanisms would seem to imply that a flow restriction due to immunopathology is in play. Any of the above could be causing that, or there may be another yet unknown mechanism.
My presentation in Prague next week will go into the immense number of changes caused by the bacterial microbiota in rather more detail than I have done before. Watch for the video online about the 24th April...
Last edited on Thu Apr 9th, 2009 15:03 by Dr Trevor Marshall
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stuckpac
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Posted: Thu Apr 9th, 2009 15:52 |
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Dr. Marshall,
Thanks for the info & links on BP and IP relationships. Will look for the videos. Good luck in Prague! I hope your presentations are well-received.
Terry
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eClaire
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Posted: Wed Apr 22nd, 2009 21:21 |
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This has been an interesting read.
One of the things I noticed is that as I became nearly totally disabled my blood pressure (always very low) approached normal or was at what is considered normal (120/70) even though I felt horrible (and my SED rate was 1).
I'm beginning to wonder about the connection between BP, increased immune function at night, and its relationship to disturbed sleep patterns.
Claire
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34mo on MP; CFS FMS MCS COPD hypermob. IBS/GERD osteopor.; 125D48 25D<4;
NoIRs during most daylight outings & covered up; home w/o NoIRs
Ph1.Dec06 * ModPh2.Jun07 * AbxBrk.Mar-May08 * Ph2.Oct-Nov08 * Ph1.Jan2009
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Jigsaw
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Posted: Sun Sep 6th, 2009 12:44 |
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What would be the advantages or disadvantages of 40mg of Benicar versus 300mg of irbesartan daily for people being put on to blood pressure medication when they are not on the MP and have no overt symptoms of chronic disease?
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MP1.Arthritis30+yrs.3/98>3X50mgdoxy/wk.6/06 limitation.9/06:Noirs.11/06:25-D,15;1,25-D,29.4.20/07:25-D.7.
2/2/07:Beni40mg,Q6H.20/2:Mino25mg,Q2-3D.3/6:Beni40,Q8H.3/8Mino50Q2-3D.3/24Mino75Q2-3D.4/16Mino100Q2D.4/29,pH2.
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Joyful
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Posted: Sun Sep 6th, 2009 12:50 |
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Hi Jigsaw.
Dr. Marshall reviewed the ARBs for this talk: Marshall TG, 2006 March
Visiting Professor Lecture Series, organized by the FDA
Molecular genomics offers new insight into the exact mechanism of action of common drugs: ARBs, statins and corticosteroids
Bethesda, MD
You may also find these links to be helpful:
Science behind Marshall Protocol
Science behind olmesartan (Benicar)
Safety of olmesartan (Benicar)
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Lyme?1980 Lyme/Babs/Bart?05 CFS?06 | Start 125D(50) 25D(32) Jun07 | Ph1Jul07 ModPh2Sep07 Ph2Feb08 Ph3Aug08 | Latest 25D(9) Apr09 | ABC of MP
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Dr Trevor Marshall
Research Team
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Posted: Sun Sep 6th, 2009 17:57 |
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Jigsaw, everybody carries the metagenomic microbiota. Only Olmesartan is a VDR agonist. Although Irbesartan will give palliation from its blocking of the Angiotensin II Type 1 Receptor, which reduces NuclearFactor-kappa-B generation, only Olmesartan can induce recovery from the microbiota that will eventually lead to either a 'middle-age' chronic disease, or a 'disease of the aging'.
Very few people die without overt signs of Th1 disease. Indeed, I keep looking, but to date every centenarian I have seen is suffering from deafness and blindness, even if not from the more obvious Th1 disorders.
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Phillyguy
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Posted: Sun Sep 6th, 2009 18:07 |
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Dr. Marshall,
Out of curiosity, how can one determine definitively that olmesartan is a VDR agonist? Is it based purely on modelling, clinical data or both? Is it something that can be calculated or is it inferred from the position it occupies in the VDR?
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