 |
| Author | Post |
|---|
Frans
Member in Phase 2
|
Posted: Sun Jul 16th, 2006 14:31 |
|
Trevor,
If I look at the Karolinska handout I see that Olmesartan is an agonist of the VDR. However, it says 'low'.
If I am not mistaken, that means that low levels activate VDR, whereas high levels don't.
Can you explain why?
Reason I ask is I am trying to convince Ellen that she should start with beni 40mg/8 hrs, but she is scared to death. That stems from last year, when she tried beni at about 10/20MG per 24 hours. She herxed like crazy then and leads her to now fear the beni. Especially at higher doses.
She doesn't react normally to any medicin. Higher mino leads to more pain, even at doses of 200MG/day. She is probably just infected to heavily.
TIA
Sincerely, Frans
PS Maybe this info is in the upcoming paper, but since I don't know when that comes out of peer review I decided to ask this question now
____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
|
Dr Trevor Marshall
Foundation Staff
|
Posted: Sun Jul 16th, 2006 16:45 |
|
Frans,
Olmesartan is an agonist of the VDR. It activates the recptor by exerting forces on both the active helices which are similar to those of 1,25-D. If the patient has high levels of 25-D then you would need a higher dose of Olmesartan to displace the 25-D from the VDR, as 25-D has a higher affinity for the receptor than does Olmesartan.
But, in general, unless the person is taking D supplements, Olmesartan activates the VDR at typical hypotensive doses. To get the palliative action of Benicar you have to use the higher doses (40mg every 6-8 hours), as different receptors are involved in the palliative actions.
The moderators now have a means to help Doc manage runaway herx, so you no longer need to fear that.
|
jrfoutin
Research Team
| Joined: | Tue Aug 9th, 2005 |
| Location: | Oregon USA |
| Posts: | 3930 |
| Status: |
Offline
|
|
Posted: Sun Jul 16th, 2006 18:16 |
|
Frans, I had a similar experience to Ellen. Prior to my official start of a full dose of Benicar, I was only able to get 30 Benicar. I was eager to begin the MP and not understanding exactly what Dr Marshall just explained, I did about the same as Ellen did and took 20mg 3x a day. I was hoping that would get me by while I found a doctor that would prescribe the full recommended amount, but thought I'd just get started on a lower dose with what I had. Silly me!
That low dose was enough to start me on my way to a magnificent neuro Herx, but not enough to protect me from the worst of it. With the good advice of Lottie and Dr Marshall the next day, I stopped the Benicar until I could get on the full 40mg 3x to 4x a day.
Like Ellen, when it came time to start the Benicar at the full recommended dose, I had some real concerns because I had experienced this horrid Herx on less. I wondered how more could be safe. But I took the leap of faith and in the time I've been on the approved MP dose for Benicar, all Herxing has been tolerable. Methods to control a runaway Herx are available now, too.
Also Frans, I thought how great it was to see you at the conference just for me. But maybe it was for Ellen too. You can tell her I am a real person that had a similar experience to hers on a sub-optimal dose, but I have been able to regain much of my health at the recommended Benicar dose.
I wish you both the best--Janet
____________________
Sarcoidosis 125D61, MP10/05 ModP2 12/05 Ph2 6/06 Ph3 10/06, NoIRs limited outings covered, 2/08 25D6.2, 10/08 25D6.9
|
Frans
Member in Phase 2
|
Posted: Thu Jul 27th, 2006 18:00 |
|
Thank you Trevor and Janet,
And yes, it has given Ellen a very good feeling to know she is not the only one having symptoms and problems and that others have had the same experiences.
Trevor, I have another question that concerns the Karolinska handout. I have shown it to some people, amongst those was our doc, and they ask me what the numbers behind the diseases mean.
Is that the number of people responding or is it the number of people who have shown progress/recovery/full recovery? Eg for ME/CFIDS it states: 77/40.
Thank you, Frans
____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
|
Dr Trevor Marshall
Foundation Staff
|
Posted: Thu Jul 27th, 2006 18:15 |
|
The larger number is the number of patients reporting in phase 2/3 who have that definitive diagnosis, along with the number who are reporting positive results already.
|
Frans
Member in Phase 2
|
Posted: Thu Jul 27th, 2006 18:27 |
|
Thank you Trevor, that is exactly what I wanted to hear/read 
Frans
____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
|
Frans
Member in Phase 2
|
Posted: Sun Jul 30th, 2006 15:04 |
|
Ok, now what I have done is make someone sleep a little less easy than before
Why? Well, we have an authority on vit. D in our little country, a certain Professor P. Lips.
To check, go to pubmed.com and type in: "lips p"[Author] including the quotes.
I thought it only prudent to inform him about dr Marshall's findings, so I sent him the Karolinska handout  I have received a notification that he read the e-mail.
I have also ent him the link to book coming up from Novascience.
Now let's see what happens... this will blow his believe system about vit. D apart I guess
Sincerely, Frans
PS I also informed JJ Kragt MD about this (also in The Netherlands). She is working on a paper about levels of 1,25D in Multiple Sclerosis, see:
- http://tinyurl.com/p4akz
Last edited on Sun Jul 30th, 2006 15:04 by Frans
____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
|
Dr Trevor Marshall
Foundation Staff
|
Posted: Sun Jul 30th, 2006 15:32 |
|
Don't bother about Dr Marjolein Drent, the chief sarcoidosis 'expert' in The Netherlands. She canned our first paper (in 2003) and wouldn't even speak with Meg and Belinda at the WASOG conference in Denver last year. Your Crown Prince is out of luck, I guess (I have heard he suffers from Sarcoidosis)
ps: actually, I guess that familial aggregation might be a particular problem in this case
|
Frans
Member in Phase 2
|
Posted: Sun Jul 30th, 2006 15:41 |
|
Trevor, I know, I have been in contact with dr D. in the past
Maybe it would be nice to rattle her cage a little more by sending a link to the new book
About our Crown Prince, you told me once. If and when my energylevels permit it, I will try to contact our Prince and bring him up-to-date, but it takes a lot of time getting all the info together to explain. They don't use email, so all has to be printed out...
Sincerely, Frans
____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
|
Dr Trevor Marshall
Foundation Staff
|
Posted: Sun Jul 30th, 2006 16:05 |
|
Don't his aides use the telephone?
I would tell them about the conference you attended where the International experts (Canada, Japan, USA) all agreed on the bacterial pathogensis for Sarcoidosis, and how you have been unable to get Marjolein interested in the past... And how she didn't even bother to attend the conference... Nor even talk about the new discoveries when she had the chance at the Denver Conference last year.
|
Frans
Member in Phase 2
|
Posted: Sun Jul 30th, 2006 16:17 |
|
| Telephone? They should, shouldn't they? Some of the most simple things keep eluding me...
____________________
Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
|
Ames
Board Staff
|
Posted: Sun Aug 6th, 2006 17:30 |
|
I think that I have a decent understanding of how 25D, 125D and Benicar affect the VDR and other receptors.
However I would like to be able to explain to people how our bacteria fit into the picture. I think you said you are not sure exactly how they disregulate our D metabolism...but perhaps you have some idea.
Does it still hold true that our bacteria convert 25D more rapidly to 1,25D (hence the altered ratio of the two D's seen in Th1 patients?)
If bacteria do cause levels of 1,25D to rise I understand how this would be detrimental to the thyriod, glutocorticoid receptors etc. However how would an increased level of 1,25D negatively affect the ability of the VDR to funtion? It seems that less 25D and more 1,25D would actually help the VDR stay more active.
Any help appreciated!
Amy
____________________
CFS/FMS/osteopenia/severe insomnia Non -MP meds: Gabitril (16 mg),Trazodone (150 mg),Tramadol (20 mg) for pain. Light: Noirs (outside and bright lights), thick layers, sunscreen
|
Dr Trevor Marshall
Foundation Staff
|
Posted: Sun Aug 6th, 2006 18:39 |
|
High levels of 1,25-D make sure the VDR continues to function fully activated. Innate immunity will mostly work fine. But higher levels will affect the Glucocortocoid receptor, which affects other immune functions, mostly in adaptive immunity.
In the last year there have been discoveries about the enzyme which makes 1,25-D from 25-D; called CYP27A1, and also experiments showing that CYP27A1 is active in macrophages, and not just CYP27B1. Another study showed that CYP24, the enzyme which breaks down 1,25-D; is expressed (controlled) by VDR activation.
D-Binding Protein (DBP) releases 25-D dependent on the presence of 1,25-D
So it is clear that the level of 25-D follows not just the simple over-usage model of years past, but is much more complex. IMO it is likely that the availability of 25-D is directly controlled by the immune system's need for that precursor.
Ingested vitamin D would upset that homeostasis.
The Bacteria feed the inflammation. They may interfer with the D metabolism directly, but I suspect that thye just feed the inflammatory reponse, and that is enough to cause the immune system to hyper-produce 1,25-D
Hope this helps
ps: here is one of the papers describing the enzyme actions:
"Metabolism of vitamin D3 by cytochromes P450"
http://tinyurl.com/lgady
Last edited on Sun Aug 6th, 2006 18:47 by Dr Trevor Marshall
|
Ames
Board Staff
|
Posted: Sun Aug 6th, 2006 20:07 |
|
Very helpful..thanks!
Wait..actually...
It seems that the presence of bacteria leads to lower levels of 25D and higher levels of 1,25D. But if this is the case I feel Th1 patients should have a very strong innate immunity response..
Can that be right? Last edited on Sun Aug 6th, 2006 20:14 by Ames
____________________
CFS/FMS/osteopenia/severe insomnia Non -MP meds: Gabitril (16 mg),Trazodone (150 mg),Tramadol (20 mg) for pain. Light: Noirs (outside and bright lights), thick layers, sunscreen
|
tickbite
Guests visiting Phase 1/2/3
|
Posted: Sun Aug 6th, 2006 21:10 |
|
I'm glad this topic is being discussed. I took this from Cell Wall Deficient Bacteria and the Marshall Protocol:
"High levels of 1,25-D allow the bacteria to colonize the phagocytes, avoiding the lysosomal phagocytosis."
It does seem that the bacteria don't necessarily have to directly control 1,25D. Bacteria just signal cytokine release, cytokines inflame, inflamation stimulates 1,25D, 1,25D allows bacteria to colonize and avoid lysosomal phagocytosis. How the bacteria avoid lysosomal phagocytosis I would like to know.
Perhaps CYP24 is being manipulated by the bacteria. Maybe CYP24 isn't expressed mainly by the VDR. It could be suppressed via another receptor in more strength.
~Greg
____________________
"Lyme","CFS", Meningitis
Phase3 8-2-07, MP on hold 11/2007
|
Dr Trevor Marshall
Foundation Staff
|
Posted: Sun Aug 6th, 2006 22:07 |
|
Greg,
I think that the way the Th1 inflammation initially overpowers the immune system, is that the level of infection gets to a critical value, and then an incident occurs (eg, sun-holiday, pregnancy, acute infection) which causes extra 1,25-D production, leading to a breakdown of the negative-feedback mechanisms which normally control the 1,25-D production in the phagocytes. From that point onwards those control mechanisms are not able to reliably maintain control. The patient enters a "relapsing-remitting" phase of the disease process.
Additionally, the TACO membrane protein, through which Mycobacteria infect the phagocyte (and possibly L-forms too), is down-regulated by VDR. So the actual entry of the bacteria into the phagocyte may be facilitated by excess ingested 25-D or Vitamin D causing the VDR to shut down.
http://tinyurl.com/nkb7x
Cholesterol is also involved in the expression of TACO:
http://tinyurl.com/l8rzj
Last edited on Sun Aug 6th, 2006 22:17 by Dr Trevor Marshall
|
tickbite
Guests visiting Phase 1/2/3
|
Posted: Sun Aug 6th, 2006 23:34 |
|
I had intially thought there was a threshold that 1,25 could be regulated to and then anything over that the feedback get's fuzzy.
In essence I take it that up to a specific threshold 1,25D keeps the VDR activated but down regulates the GCR, adaptive immunity if 1,25D is above that threshold.
Hyper-produced 1,25D keeps the negative feedback from expressing CYP24 that causes breakdown of 1,25D. On top of that, ingesting 25D inactivates the VDR causing CYP24 to not be expressed. That's how 25D (and cholesterol) facilitates the process by which the TACO membrane protein is down regulated and colonization takes place along with avoiding lysosomal phagocytosis. That is, if L-Forms use the TACO membrane protein. Is there anyone looking to find it? Are we talking about the protein shell around the colony or larger form or cyst? Why do we call it "biofilm"? I thought the term biofilm represented a group of larger Prokaryotes in colony extracellularly. Is it correct to say that intracellular bacterial colonies have a biofilm?
Sorry if it's all jumbled or wrong  I'm just trying to learn.
~Greg
Last edited on Mon Aug 7th, 2006 01:35 by tickbite
____________________
"Lyme","CFS", Meningitis
Phase3 8-2-07, MP on hold 11/2007
|
tickbite
Guests visiting Phase 1/2/3
|
Posted: Tue Aug 22nd, 2006 23:42 |
|
| Nevermind I'm jumbled. I figure I need to finish reading Lida and Alan's books amongst everything else. I'm intrigued that Alan mentions Edgar Cayce in his book "The Cancer Microbe". Bizarre how his name keeps coming up. I'm so happy to be reading the history of filterable forms and mycobacteria.
____________________
"Lyme","CFS", Meningitis
Phase3 8-2-07, MP on hold 11/2007
|
Dr Trevor Marshall
Foundation Staff
|
Posted: Wed Aug 23rd, 2006 01:20 |
|
Greg,
Let me explain it this way. When every VDR receptor is occupied by a 1,25-D molecule you have a saturated VDR subsystem. At that point CYP24 would be up-regulated to maximum (assuming VDR is the primary regulation of CYPR24, which is currently believed) and that would tend to catalyze any unbound 1,25-D to oxidize to inactive 24,25-D 25,26-D and 25-D.
If the 1,25-D keeps being hyper-expressed beyond this level, maybe by excessive solar exposure, pregnancy, or by a bacteria-induced catalysis, then the higher 1,25-D concentrations will progressively affect GCR and Thyroid receptors. Perhaps by ths point those receptors are already heavily occupied with 1,25-D it would depend on their native metabolite, and factors we can't yet quantify.
I hope this helps
..Trevor..
|
scooker48
Member in Phase 3
|
Posted: Wed Aug 23rd, 2006 19:01 |
|
This fits with my experience. In July 2002 I took a sun holiday up in Alaska for 1 week. After coming home I had an operation (partial hyster) some 10 days later. Although I thought I recovered nicely from that surgery (my first and only) my overall energy level decreased as my brain fog increased. I took another Alaskan vacation in August 2004. Sarcoidosis was diagnosed in December 2004.
Possibly it is coincidence, but it fits the pattern.
Sherry
____________________
Necrotizing granulomas biopsy 10/88; Dx 12/04 Sarcoid liver spleen. 2/2/05: VitD 25/VitD125 62. 11/7/09 D25 at 6, Liver function normal 4/08; Wear NoIRs outside. No K creme used. 5/09 Liver and kidneys normal. ACE still high at 113 on 11/7/09.
|
Current time is 18:58 | Page:   1 2 3 4   |
|
|
|
|
