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Autoimmune and the VDR vitamin d receptor

Discussion in 'Adrenal Rx and Leaky Gut Rx' started by chocolate, Apr 21, 2012.

  1. chocolate

    chocolate Silver

    http://autoimmunityresearch.org/dmm2008/DMM2008_Marshall.pdf



    During DMM 2006 we reported that chronic inflammatory disease, including much 'autoimmune' disease, was caused by an intraphagocytic biofilm-like microbiota. Recovery followed activation of the VDR with Olmesartan, and long-term administration of subinhibitory antibiotics. Surprisingly, as the inflammatory disease disappeared from the subjects in that cohort, manifestations of comorbid neurological disease also receded. Memory and cognition returned as the inflammation waned, while suicidal ideation, depression, bipolar disorder, peripheral neuropathies and even obsessive compulsive disorder, receded. Additionally, we found that the neurological symptoms fluctuated with the level of Immunopathology during the healing process, presenting special problems with cohort management. The VDR is at the heart of the innate immune system, responsible for expression of a majority of the body's antimicrobial peptides [1]. Changes in lifestyle and medicine during the 20th century have created an environment favorable to the proliferation of pathogens which evade the immune system by suppressing activation of the VDR [2]. Kandel identified that short term memory involves activation of PKA [3]. We have determined that activation of PKA is regulated by the process of VDR homeostasis in chronic immune disease, pointing towards a putative mechanism whereby immune dysfunction can directly suppress short-term memory. However the above subjects not only reported the return of short term memory, but also of mid-term and long-term memory. The molecular mechanisms linking immune dysfunction and cognitive dysfunction are clearly profound. We propose that studies of linked dysfunction will provide more insight than studies of neurological manifestations alone.

    1. Marshall TG: Vitamin D discovery outpaces FDA decision making. Bioessays. 2008 Feb;30(2):173-82

    2. Marshall TG: Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides. Abstract presentation, Metagenomics 2007, San Diego, July 11-13, 2007.

    DOI 10.1038/npre.2007.164.1

    Available from URL http://autoimmunityresearch.org/transcripts/metagenomics2007pdf

    3. Eric





    I read a later article that says antibiotics are no longer necessary.
     
  2. chocolate

    chocolate Silver

    http://mpkb.org/home/publications/marshall_dnaday2011



    Presentation - The human microbiome lies at the heart of autoimmune disease



    Nice Video. Oz is holding out.



    Type: Conference presentation

    Presenter: Trevor Marshall, PhD

    Conference: BIT's 2nd World DNA and Genome Day

    Location: Dailan, China

    Date: May 2011
     
  3. chocolate

    chocolate Silver

  4. chocolate

    chocolate Silver

    http://www.ncbi.nlm.nih.gov/pubmed/22247605Exogenously-added copper/zinc superoxide dismutase rescues damage of endothelial cells from lethal irradiation.



    Abstract



    The vascular endothelium is important for the early and late effects observed in lethally irradiated tissue and organs. We examined the effects of exogenously added superoxide dismutase on cell survival and angiogenesis in lethally irradiated human primary umbilical vein endothelial cells. Cell survival was significantly improved in superoxide dismutase-treated cells; the addition of superoxide dismutase to cells after irradiation was also effective for increased survival, as it was before irradiation. Moreover, treatment of cells with superoxide dismutase enhanced the phosphorylation of mitogen-activated protein/extracellular signal-regulated kinase/extracellular signal regulated kinases 1 and 2 in human primary umbilical vein endothelial cells. The addition of superoxide dismutase to cells after irradiation attenuated the reduction of angiogenesis by irradiation, and inhibition of the mitogen-activated protein/extracellular signal-regulated kinase/extracellular signal regulated kinases signaling pathway abrogated the rescue effect of superoxide dismutase. Our results suggest that superoxide dismutase rescues human primary umbilical vein endothelial cells from endothelial dysfunction caused by irradiation via a pathway requiring activation of mitogen-activated protein/extracellular signal-regulated kinase/extracellular signal regulated kinases 1 and 2.
     
  5. Joann

    Joann New Member




    interesting! chocolate, what do you think happens when one takes vit d if VDR is blocked?
     
  6. Jack Kruse

    Jack Kruse Administrator

    The finding, published in the May 23, 2012 online issue of Science Translational Medicine, more fully explains how the immune system functions in different situations and presents a new avenue for treating infections, perhaps as an alternative to current antibiotic therapies (see also Skin Cancer).



    The immunological benefits of vitamin D are controversial. In cultured cell studies, the fat-soluble vitamin provides strong immunological benefits, but in repeated studies with humans and animal models, results have been inconsistent: People with low levels of dietary vitamin D do not suffer more infections. For reasons unknown, their immune response generally remains strong, undermining the touted immunological strength of vitamin D.



    Working with a mouse model and cultured human cells, Gallo and colleagues discovered why: When levels of dietary vitamin D are low (it's naturally present in very few foods), production of parathyroid hormone (PTH), which normally helps modulate calcium levels in blood, is ramped up. More PTH or a related peptide called PHTrP spurs increased expression of AMPs, such as cathelicidin, which kill a broad spectrum of harmful bacteria, fungi and viruses.



    "No one suspected a role for PTH or the PTH-related peptide in immunity," said Richard L. Gallo, MD, PhD, professor of medicine and chief of UCSD's Division of Dermatology and the Dermatology section of the Veterans Affairs San Diego Healthcare System. "This may help resolve some of the controversy surrounding vitamin D. It fills in the blanks."



    For example, the findings relate to the on-going debate over sun exposure. Sunlight triggers the production of vitamin D. Low levels of vitamin D have been claimed in some studies to increase the risk of cardiovascular disease and cancer, but other studies have failed to confirm this. On the other hand, high levels of solar exposure that could increase vitamin D have been shown to increase the risk of skin cancer.



    "Since sunlight is a carcinogen, it's a bad idea to get too much of it," said Gallo. "PTH goes up when levels of vitamin D from diet and sun exposure are low. PTH may be what permits us to have low D in the diet and not kill ourselves with too much UV radiation."



    Gallo said PTH's newly revealed immunological role provides a new connection between the body's endocrine system (a system of glands secreting different regulatory hormones into the bloodstream) and its ability to fight invasive, health-harming pathogens.
     
  7. chocolate

    chocolate Silver

    Are you kidding me? I'm starting to think yeast is good. It follows the bad guys through the zonulin

     
  8. chocolate

    chocolate Silver

    http://stroke.ahajournals.org/content/25/1/165.short

    Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia



    CONCLUSIONS--Our study demonstrated that superoxide radicals play a major role in the pathogenesis of cerebral infarction in reperfusion injury after a focal stroke. The reduction in infarct volume and neurological deficits is not dependent on the changes in cerebral blood flow but rather correlate with reduced oxidative stress in the ischemic brain tissue, which was indicated by the relatively high levels of endogenous reduced glutathione in transgenic mice.
     
  9. chocolate

    chocolate Silver


    I was looking at the tagamet and it mentioned that it was good for parathyroid storm..... which is what sung to my soul... then I saw that it caused an increase in yeast. which is odd, because the kids in college take it to suppress rosacea when they drink... I'm not thinking this through properly.
     
  10. Joann

    Joann New Member


    Marshall also stated...lactobacillus was responsible for ACE (angiotensin converting enzyme)

    which is not a good thing. inflammation?
     
  11. chocolate

    chocolate Silver

    Copper/Zinc Superoxide Dismutase Insufficiency Impairs Progesterone Secretion and Fertility in Female Mice1



    http://www.biolreprod.org/content/86/1/1.16



    Copper/zinc superoxide dismutase (CuZn-SOD, SOD1) is one of the major antioxidant enzymes, and is localized in the cytoplasm to scavenge superoxide. To investigate the physiological role of SOD1 in the ovaries, we analyzed the fertility of Sod1-deficient female mice. To evaluate their hormonal metabolism, we measured pituitary and ovarian hormone levels in the plasma of the mutant mice. Plasma follicle-stimulating hormone, luteinizing hormone, and estradiol were not altered in the mutant compared to the wild-type females, while the plasma progesterone level was significantly reduced in the mutant females. Furthermore, the mutant mice showed decreased progesterone secretion under the condition of superovulation. In a histochemical analysis, we observed a remarkable reduction in the corpus luteum area in the mutant ovaries without atrophic changes. The mutant mice also displayed enhanced superoxide generation in the region surrounding the corpora lutea, which was associated with increased apoptotic cells and suppressed vasculature. These results suggested that SOD1 deficiency dysregulated luteal formation because of increased superoxide generation in the ovary. In vitro fertilization experiments showed no abnormal fertilization of Sod1-deficient oocytes. In addition, when Sod1-deficient embryos were transferred into the oviducts of wild-type females, mutant embryos developed at a normal rate, indicating that SOD1 deficiency in embryos did not cause miscarriage in the uterus of wild-type females. These results indicated that increased intracellular ROS impaired luteal formation and progesterone production in the mutant females, thus suggesting that SOD1 plays a crucial role in both the luteal function and the maintenance of fertility in female mice.





    I guess a vaginal yeast infection could come in handy. cough, cough
     
  12. chocolate

    chocolate Silver

    I think the candida is our winter immune system, or at least a part of it. I do think we need to activate the vdr , if we can. All of the vitamins that are deficient are irrelevant in a hibernated state. How much digesting do you need to do if you don't eat and how much emotional composure do you need to sleep? I guess you just need enough b-6 to dream. In a hibernated state, you don't need meat. I was reading or some posted a blog about seaweed having a b-12 claw.... maybe yeast is our seaweed.



    http://www.livestrong.com/article/453954-brewers-yeast-vitamin-b12/



    Yeast comes in several forms -- including brewer's yeast in dried powder or tablets. The name comes from its use in brewing alcoholic beverages such as beer. Health stores offer brewer's yeast as a dietary supplement rich in B vitamins, even though only fortified brewer's yeast has vitamin B12. (fortified)

    B12



    Vitamin B12 plays an important role in metabolism, the nervous system and the creation of red blood cells, according to the University of Maryland Medical Center. A very complex vitamin, B12 occurs in many animal products, including dairy foods, fish and meat. Most people get enough B12 from their diet, although vegans may not. In addition 10 to 15 percent of those who are 60 and older are deficient in B12, according to Dr. Jane Higdon of the Linus Pauling Institute.




    Read more: http://www.livestrong.com/article/453954-brewers-yeast-vitamin-b12/#ixzz1wecVNHBB
     
  13. chocolate

    chocolate Silver

    http://www.nutritionalwellness.com/nutrition/herbs/s/seaweed.php



    In addition to its culinary uses, seaweed is an important medicinal. Most seaweed is high in vitamin B12 and iodine. Other minerals found in seaweed include copper, iron, magnesium, calcium, potassium, and zinc. Because seaweed contains all of these nutrients, it is sometimes referred to as "nature's treasure chest."



    Seaweed has salty and cold properties, and is associated with the Liver, Stomach and Kidney meridians, according to the precepts of traditional Chinese medicine. It helps to treat skin and glandular conditions such as iodine deficiency, goiter and scrofula; reduces the incidence of edema; and is effective against bronchitis and coughs. It also helps blood cells to coagulate, and may inhibit the growth of some types of cancerous tumors.
     
  14. chocolate

    chocolate Silver

    http://www.ncbi.nlm.nih.gov/pubmed/20371703

    A novel bile acid-activated vitamin D receptor signaling in human hepatocytes.

    Abstract



    Vitamin D receptor (VDR) is activated by natural ligands, 1alpha, 25-dihydroxy-vitamin D(3) [1alpha,25(OH)(2)-D(3)] and lithocholic acid (LCA). Our previous study shows that VDR is expressed in human hepatocytes, and VDR ligands inhibit bile acid synthesis and transcription of the gene encoding cholesterol 7alpha-hydroxylase (CYP7A1). Primary human hepatocytes were used to study LCA and 1alpha,25(OH)(2)-D(3) activation of VDR signaling. Confocal immunofluorescent microscopy imaging and immunoblot analysis showed that LCA and 1alpha, 25(OH)(2)-D(3) induced intracellular translocation of VDR from the cytosol to the nucleus and also plasma membrane where VDR colocalized with caveolin-1. VDR ligands induced tyrosine phosphorylation of c-Src and VDR and their interaction. Inhibition of c-Src abrogated VDR ligand-dependent inhibition of CYP7A1 mRNA expression. Kinase assays showed that VDR ligands specifically activated the c-Raf/MEK1/2/extracellular signal-regulated kinase (ERK) 1/2 pathway, which stimulates serine phosphorylation of VDR and hepatocyte nuclear factor-4alpha, and their interaction. Mammalian two-hybrid assays showed a VDR ligand-dependent interaction of nuclear receptor corepressor-1 and silencing mediator of retinoid and thyroid with VDR/retinoid X receptor-alpha (RXRalpha). Chromatin immunoprecipitation assays revealed that an ERK1/2 inhibitor reversed VDR ligand-induced recruitment of VDR, RXRalpha, and corepressors to human CYP7A1 promoter. In conclusion, VDR ligands activate membrane VDR signaling to activate the MEK1/2/ERK1/2 pathway, which stimulates nuclear VDR/RXRalpha recruitment of corepressors to inhibit CYP7A1 gene transcription in human hepatocytes. This membrane VDR-signaling pathway may be activated by bile acids to inhibit bile acid synthesis as a rapid response to protect hepatocytes from cholestatic liver injury.




    Vitamin D receptor (VDR) is activated by natural ligands, 1alpha, 25-dihydroxy-vitamin D(3) [1alpha,25(OH)(2)-D(3)] and lithocholic acid (LCA)
     
  15. chocolate

    chocolate Silver

    lithocolic acid

    http://www.medicalnewstoday.com/articles/240076.php



    Lithocholic Acid Kills Cancer Cells But Not Healthy Cells

    The abilities of an acid that is naturally produced in the liver during digestion, called Lithocholic acid (LCA) have seriously been underestimated until now. According to a study led by Concordia University published in Oncotarget, LCA can kill several types of cancer cells, including those found in some brain tumors and breast cancer.



    The research team, which included scientists from McGill University and the Jewish General Hospital's Lady Davis Institute in Montreal as well as the University of Saskatchewan established in earlier research that LCA also extends the lifespan of aging yeast. In the new study the team discovered that LCA is very selective in killing cancer cells whilst leaving normal cells unharmed. The discovery could pave the way for a major improvement of existing chemotherapy drugs.



    Senior author Vladimir Titorenko, a professor in the Department of Biology and Concordia University Research Chair in Genomics, Cell Biology and Aging declared:



    "LCA doesn't just kill individual cancer cells. It could also prevent the entire tumor from growing."







    Furthermore, LCA stops tumors from releasing substances that cause growth and proliferation in neighboring cancer cells. According to Titorenko LCA is the only compound able to targets cancer cells, which could mean that it has the power to halt tumors.



    He declares: "This is important for preventing cancer cells from spreading to other parts of the body," and points out that unlike other anti-aging compounds, LCA prevents the growth of cancer cells but still allows normal cells to continue to grow.

    A wide effect on different types of cancers

    The team will be testing LCA's effects on different cancers in mice models in their future research. Titorenko anticipates that the LCA will also kill cancer cells in those experiments and subsequently lead to human clinical trials.



    He says:



    "Our study found that LCA kills not only tumors (neuroblastomas), but also human breast cancer cells. This shows that it has a wide effect on different types of cancers."








    Titorenko highlights that in contrast to current drugs used in chemotherapy, LCA is a natural compound that is already present in our bodies.



    Studies have proven that LCA can be safely administered to mice by adding it to their food, which raises the question to why LCA is so deadly for cancer cells? According to Titorenko belief cancer cells possess more sensors for LCA, making them more sensitive to the compound compared with normal cells. 





    LCA sensors transmit signals to mitochondria, the powerhouses of all cells, and it appears that when these signals are too strong, the mitochondria self-destruct bringing the cell down with them. To put it simply Titorenko and his team engaged in cancer cell sabotage by employing LCA to target weaknesses in cancerous cells.



    The study was funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Concordia University Research Chair program.



    I gotta git me sum o dis.
     
  16. chocolate

    chocolate Silver

    Lithocholic acid (LCA) is a bile acid that acts as a detergent to solubilize fats for absorption. Bacterial action in the colon produces LCA from chenodeoxycholic acid by reduction of the hydroxyl functional group at carbon-7 in the "B" ring of the steroid framework.



    http://en.wikipedia.org/wiki/Lithocholic_acid

    It has been implicated in human and experimental animal carcinogenesis.[2] Preliminary in vitro research suggests that LCA selectively kills neuroblastoma cells, while sparing normal neuronal cells.[3]



    Dietary fiber can bind to lithocholic acid and aid in its excretion in stool;[4] as such, fiber can protect against colon cancer.



    LCA (and LCA acetate and LCA propionate) can activate the vitamin D receptor without raising calcium levels as much as vitamin D itself.[5
    ]
     
  17. chocolate

    chocolate Silver

    http://spectrum.library.concordia.ca/6993/

    Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes



    I think this might imply that the yeast is stealing or diverting the LCA away from the VDR, or something.
     
  18. chocolate

    chocolate Silver

    http://www.ncbi.nlm.nih.gov/pubmed/16816478

    [Vitamin D-vitamin D receptor system regulates antithrombogenicity in vivo].

    [Article in Japanese]

    Aihara K, Azuma H, Matsumoto T.

    Source



    The University of Tokushima Graduate School, Institute of Health Biosciences, Department of Medicine and Bioregulatory Sciences.

    Abstract



    Although it has been well documented that vitamin D receptor (VDR) activation influences the expression of various genes involved in calcium homeostasis and cell differentiation, the physiological role of VDR action in hemostasis remains unclear. We studied thrombogenicity in normocalcemic VDR knock-out (KO) mice on a high calcium diet in comparison with that in wild-type mice and that in hypocalcemic VDRKO mice fed a regular diet. Platelet aggregation was significantly enhanced in normocalcemic VDRKO mice. Aortic endothelial nitric-oxide (NO) synthase expression and urinary NOx excretion were reduced in hypocalcemic VDRKO mice but not in normocalcemic VDRKO mice. The gene expression of antithrombin in the liver and that of thrombomodulin in the aorta, liver and kidney were down-regulated in hypo- and normocalcemic VDRKO mice, whereas tissue factor gene expression in the liver and kidney was up-regulated in VDRKO mice regardless of plasma calcium level. Furthermore, VDRKO mice manifested an exacerbated multi-organ thrombus formation after exogenous lipopolysaccharide injection regardless of the calcemic conditions. These results demonstrate that the vitamin D-VDR system plays a pivotal role in antithrombogenicity in vivo.
     
  19. chocolate

    chocolate Silver


    Licorice is an angiotensin II receptor agonist and definitely makes a lot of urine.
     
  20. chocolate

    chocolate Silver

    http://www.sciencedirect.com/science/article/pii/S0039128X06000183

     

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