The Marshall Protocol Study Site Home

Search
   
Members

Calendar

Help

Home
Search by username
   Not logged in - Login | Register 


Vitamin D Receptor
 Moderated by: Prof Trevor Marshall
 

New Topic

Reply

Print
AuthorPost
migsies
inactive member


Joined: Sat Mar 26th, 2005
Location: Gainesville, Florida USA
Posts: 101
Status:  Offline
 Posted: Sat Feb 3rd, 2007 14:43

Quote

Reply
Thought some of you might find this study interesting as it offers additional confirmation that elevated levels of D3 lead to compromised innate immunity!

Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns



____________________
Sarcoidosis FM Lyme babesia 25D>7(Feb07) Ph1Aug05 Ph2Oct05 Ph3 Jun06 Valium Lyrica Ambien NoIRs limited outings covered Phase I 8/05, II 10/05, III 6/06.
paulalbert
Research Team


Joined: Thu Jul 15th, 2004
Location: New York USA
Posts: 1034
Status:  Offline
 Posted: Sat Feb 3rd, 2007 14:56

Quote

Reply
This article looks really interesting!

Paul



____________________
Diag CFS 6.03 / sympt since 9.02 / exercise, food intol, sleep prob / 1,25D: 16, 4.06; 1,25D:27, 25D:26 7.04; 1,25D:43, 25D:6 6.05; 1,25D:17, 25D:8 8.05; / MP: 7.04 / Ph. 3 / Bacteriality
migsies
inactive member


Joined: Sat Mar 26th, 2005
Location: Gainesville, Florida USA
Posts: 101
Status:  Offline
 Posted: Sat Feb 3rd, 2007 18:17

Quote

Reply
I am suddenly wondering whether benicar is involved in a finely tuned balancing act, caught between upregulation of the pertinent TLR's required for CWD eradication, via it's interaction with the VDR, and downregulation of inflammatory cytokines via interference with the angiotensin II receptors???? Is it possible to have TLR-4 activation via VDR without incurring the wrath of long term inflammation, and is benicar succesful in this regard? This may be the 64,000 dollar question! Regardless, it seems that without elminating the offending critters, as proposed by the MP, the only prospects are for chronic low grade inflammation and CWD proliferation, leading to a grim prognosis.

Incidentally, despite a year and a half on the MP, I am still uncertain as to whether benicar is behaving as a VDR antagonist, or rather an agonist. The latter would make more sense to me in the context of this article, although, there are probably nuances that I am missing. Perhaps someone can clear this up for me, as my brain-fogged mind is in need of assistance when it comes to cognitive processing.:cool:



____________________
Sarcoidosis FM Lyme babesia 25D>7(Feb07) Ph1Aug05 Ph2Oct05 Ph3 Jun06 Valium Lyrica Ambien NoIRs limited outings covered Phase I 8/05, II 10/05, III 6/06.
paulalbert
Research Team


Joined: Thu Jul 15th, 2004
Location: New York USA
Posts: 1034
Status:  Offline
 Posted: Sat Feb 3rd, 2007 18:27

Quote

Reply
Don't know the answers to your other questions... but Benicar is an agonist.

P

Last edited on Sat Feb 3rd, 2007 18:27 by paulalbert



____________________
Diag CFS 6.03 / sympt since 9.02 / exercise, food intol, sleep prob / 1,25D: 16, 4.06; 1,25D:27, 25D:26 7.04; 1,25D:43, 25D:6 6.05; 1,25D:17, 25D:8 8.05; / MP: 7.04 / Ph. 3 / Bacteriality
Prof Trevor Marshall
Foundation Staff


Joined: Fri Jul 9th, 2004
Location: Thousand Oaks, California USA
Posts: 15742
Status:  Offline
 Posted: Sat Feb 3rd, 2007 19:00

Quote

Reply
Migsies,
First, I would note that the modulation of the TLR by VDR was mentioned by me in my Karolinska abstract at URL
http://autoimmunityresearch.org/karolinska-abstract.pdf

I am not necessarily trying to discourage you posting Pubmed abstracts, but you would have gained this insight some time ago with more focused research, taking into account what is already written in my previous publications, and in my 'perspective'
http://www.marshallprotocol.com/forum39/

Olmesartan is a partial agonist and antagonist of many, many receptors. Basically, almost anything that 1,25-D targets is also a potential target for Olmesartan. Those receptors range from Rhodopsin GPCR (in the eyes) through to the Type 1 nuclear receptors (all of them, but particularly VDR, GCR, MCR, Progesterone and Thyroid), all the way to the Angiotensin GPCR.

Most drugs have a wide spectrum of effect, but in those cases we know very little about their effects until the FDA reports "adverse events" like heart attacks, or whatever.

By contrast, I have explored the effects of Olmesartan on a wide variety of body systems using the most advanced modeling technology available to science. I also watch the literature for signs of clinical studies whih would send me scurrying back to my lab, or alternatively, give me a "Eureka" moment.

I am continually fed study results by my professional colleagues, from all around the world, and we carry on a vigorous discussion, out of the public spotlight, and at conferences.

I cannot promise that there is nothing we have missed, but anytime that just one of the thousands of patients on the MP, or their physicians, report a problem, we look at it as a matter of priority. The FDA is not so zealous.

Finally, it is just not possible to try and understand TLR signalling in the immune system, or DNA transcription by the nuclear recptors, without many years of study, and thorough understanding of research methodology. PubMed is a wonderful resource, but what you read there has to be read with the skeptical eye of a university professor. Unless you know where the mistakes are likely to have been made, you will not be able to extend knowledge from the data published by others. Everybody makes mistakes, even me. You will note that our Dec 2005 paper says that Benicar is an atagonist for the VDR. 99% of ligands act as antagonists, so this is always the initial assumption. However, my later work showed the path for its agonistic effects, and my views had to change in accord with the advancing science...

migsies
inactive member


Joined: Sat Mar 26th, 2005
Location: Gainesville, Florida USA
Posts: 101
Status:  Offline
 Posted: Sat Feb 3rd, 2007 19:29

Quote

Reply
Thanks for shedding light on this topic! If I am overly curious, it is because I come from a background in molecular evolution and because I have a personal vested interest as a victim of Th1 illness. I agree, scientific knowledge should always be subject to revision and examined with a discerning mind.;)



____________________
Sarcoidosis FM Lyme babesia 25D>7(Feb07) Ph1Aug05 Ph2Oct05 Ph3 Jun06 Valium Lyrica Ambien NoIRs limited outings covered Phase I 8/05, II 10/05, III 6/06.
wrotek
member


Joined: Thu Dec 30th, 2004
Location: Wroclaw, Poland
Posts: 2915
Status:  Offline
 Posted: Mon Sep 3rd, 2007 13:26

Quote

Reply
Neophobia, sensory and cognitive functions, and hedonic responses in vitamin D receptor mutant mice.
Minasyan A, Keisala T, Lou YR, Kalueff AV, Tuohimaa P. Department of Anatomy, Medical School, University of Tampere, Tampere 33014, Finland. anna.minasyan@uta.fi

Vitamin D is a seco-steroid hormone with multiple actions in the brain, mediated through the nuclear vitamin D receptor (VDR). We have recently shown that mutant mice lacking functional VDR demonstrate altered emotional behavior and specific motor deficits. Here we further examine phenotype of these mice, testing their novelty responses, as well as cognitive and sensory (olfactory and gustatory) functions in the novel food, two-trial Y-maze and tastant consumption tests. In addition, we study depression-like behavior in these mice, using anhedonia-based sucrose preference test. Overall, VDR mutant mice showed neophobic response in several different tests, but displayed unimpaired olfactory and gustatory functions, spatial memory and baseline hedonic responses. Collectively, these data confirm that mutation of VDR in mice leads to altering emotional/anxiety states, but does not play a major role in depression, as well as in the regulation of some sensory and cognitive processes. These results support the role of the vitamin D/VDR neuroendocrine system in the regulation of behavior, and may have clinical relevance, enabling a better focus on psychiatric and behavioral disorders associated with dysfunctions in this neuroendocrine system.
PMID: 17482806 [PubMed - indexed for MEDLINE]
http://tinyurl.com/2tg9rr


Behavioural anomalies in mice evoked by "Tokyo" disruption of the Vitamin D receptor gene.
Kalueff AV, Keisala T, Minasyan A, Kuuslahti M, Miettinen S, Tuohimaa P. Medical School, University of Tampere, Finland. avkalueff@inbox.ru

Vitamin D is a steroid hormone with many important functions in the brain, mediated through the nuclear Vitamin D receptor (VDR). Mounting clinical data link VDR mutations to various psychiatric phenotypes. We have reported previously that mutant mice lacking functional VDR ("Tokyo" VDR mutant mice) display several behavioural anomalies, including high anxiety and aberrant grooming. Given the important role of Vitamin D and VDR in brain development and functioning, we hypothesized that several other important behavioural domains may be affected by disruption of the VDR gene in mice. Here we report that VDR mutants display unaffected depressive-like behaviour, but show abnormal social behaviours, reduced social barbering and aggressiveness, impaired nest building and aberrant maternal (pup neglect, cannibalism) behaviours. Taken together, these findings confirm the important role postulated for the VDR in the regulation of behaviour, and suggest the mice lacking functional VDR may be a useful tool to model different brain disorders.
PMID: 16427152 [PubMed - indexed for MEDLINE]
http://tinyurl.com/37hvxk

-------------
Hmmm is not it interesting ?

Last edited on Mon Sep 3rd, 2007 15:13 by Prof Trevor Marshall



____________________
Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 in low lux NoIRs 25D<7 Oct06
Prof Trevor Marshall
Foundation Staff


Joined: Fri Jul 9th, 2004
Location: Thousand Oaks, California USA
Posts: 15742
Status:  Offline
 Posted: Mon Sep 3rd, 2007 15:11

Quote

Reply
Here is another:

"Aberrant nest building and prolactin secretion in vitamin D receptor mutant mice."
http://tinyurl.com/2khpsz

wrotek
member


Joined: Thu Dec 30th, 2004
Location: Wroclaw, Poland
Posts: 2915
Status:  Offline
 Posted: Wed Oct 17th, 2007 10:48

Quote

Reply

Increased severity of chemically induced seizures in mice with partially deleted Vitamin D receptor gene
http://tinyurl.com/2xlsbj 

Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury
http://tinyurl.com/yt2q9e

Impaired motor performance in mice lacking neurosteroid vitamin D receptors
http://tinyurl.com/yqq3qv
(Perhaps this will be relevant for motor neuron disease )

http://tinyurl.com/2zq8cf
Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure.

Clinical and epidemiological studies have suggested a correlation between Vitamin D-deficiency and high blood pressure. Our recent studies demonstrate that Vitamin D is a potent endocrine suppressor of renin biosynthesis to regulate the RAS. Mice lacking the Vitamin D receptor (VDR) have elevated production of renin and angiotensin (Ang) II, leading to hypertension, cardiac hypertrophy and increased water intake. These abnormalities can be prevented by treatment with an ACE inhibitor or AT(1) receptor antagonist.
http://tinyurl.com/25no9z
Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems

" Our recent studies suggest that 1,25-dihydroxyvitamin D3 functions as an endocrine suppressor of renin biosynthesis. Genetic disruption of the vitamin D receptor (VDR) results in overstimulation of the renin-angiotensin system (RAS), leading to high blood pressure and cardiac hypertrophy."
Effect of Angiotensin II Type I Receptor Antagonist and Angiotensin-Converting Enzyme
Inhibitor on Vitamin D Receptor Null Mice
http://ajpregu.physiology.org/cgi/reprint/00517.2002v1.pdf
We have recently shown that vitamin D receptor (VDR) inactivation results in deregulated stimulation of the renin-angiotensin system (RAS). To address further the relationship between RAS activation and the abnormalities in electrolyte and volume homeostasis, we studied the effect of AT1 receptor antagonist losartan and angiotensin-converting enzyme inhibitor captopril on VDR-null mice. Treatment with losartan or captopril normalized the water intake and urine excretion of VDR-null mice. However, the increase in salt excretion in VDR-null mice was not affected by either drug, suggesting that this abnormality is independent of the RAS.
:)

Last edited on Wed Oct 17th, 2007 14:34 by wrotek



____________________
Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 in low lux NoIRs 25D<7 Oct06

 Current time is 16:29



* We can help you understand chronic disease, but only your physician is licensed to give you medical care *

Powered by WowBB 1.7 - Entire site Copyright © 2004-2020 Autoimmunity Research Foundation, All Rights Reserved
Click here to view our PRIVACY POLICY
Page processed in 0.0414 seconds (75% database + 25% PHP). 18 queries executed.