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The most interesting news about vitamin D for pharmacologists. London 17.09.20111 Author: Dr. Anna Dorothea Höck E-Mail: [email protected]. Old. New. Genomic (via gene expression ) - PowerPoint PPT Presentation
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LONDON 17.09.20111AUTHOR: DR. ANNA DOROTHEA HÖCK
E-MAIL: [email protected]
The most interesting news about vitamin D for
pharmacologists
Old New
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Genomic (via gene expression)Pike JW, et al. Endocrinol Metab Clin North Am 2010;39(2):255-69
Pan YZ, et al. Drug Metab Dispos 2009;37(10):2112-7 Komagata S, et al. Mol Pharmcol 2009; 76(4):702-9
Non-genomic (via cell-signaling)Yu C, et al. Int J Biochem Cell Biol 2011;43(1):41-6
Shin JS, et al. Zhao G, et al. Steroids 2010;75(8-9):555-9Dixon KM, et al. J Steroid Mol Biol 2007;103(3-5):451-6
NEW:
Non-genomic actions seem to be necessary for genomic actions
Ordonez-Moran, et al. Cell cycle 2009;8(11):1675-80
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Theman TA, et al. Curr Pharm Biotechnol 2009;10(3):289-301
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Well known: New:
Löffler G, Petrides PE, 8th edition, Springer, Germany
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KNOWN
AND IMAGINABLE
CONSEQUENCES
OF CALCIUM DEFICIENCY
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The complexity of calcium metabolism
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Löffler G, Petrides PE, 8th edition, Springer, Germany
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London 18.09.2011Harrison‘s Principles of Medicine. 17th edition.
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Low calcium stores High calcium Stores
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Bone resorption is hyperactive (a proinflammatory event).
Fleet JC. J Musculoskelet Neuronal Interact 2006:6(4):336-7.
Strong innate immune system and regulated, modulated and mitigated adaptive immune system.
Panda DK, et al. PNAS 2001;89:7498-7503.Peterlik M, et al. Eur J Clin Invest 2005;35(5):290-304.
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A possible link between calcium deficiency and inflammation
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Cadherin superfamily
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Cadherin with Calcium and without
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Role of calcium in muscle
Vortrag in Bergisch-Gladbach 10/2011
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Ca/Tropomyosin enables muscle contraction
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Vortrag in Bergisch-Gladbach 10/2011
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Role of calcium in nerve signaling
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1. IMMUNE SYSTEM
2. REDOX SYSTEM
3. EFFECTS ON MITOCHONDRIA
4. EFFECTS ON HEART AND KIDNEY
5. EFFECTS ON AMINO ACIDS AND POLYAMINES
6. EFFECTS ON BRAIN
7. AUTORADIOGRAPHIC VITAMIN D TARGETS
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The pleiotropic organ protection of vitamin D
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ENHANCES INNATE IMMUNE SYSTEM
REGULATES AND MODULATES ADAPTIVE IMMUNE SYSTEM
Effects of vitamin D on immune system
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REDUCES OXIDATIVE STRESS
REDUCES REDUCTIVE STRESS
Effects of vitamin D on redox-system
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MITOCHONDRIA AS A POSSIBLE MAJOR LINK BETWEEN VITAMIN D DEFICIENCY AND ENERGY DEFICIENCY (FATIGUE)?
Effects of vitamin D on mitochondria
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MOST PUBLICATIONS NOW OUTDATED.
A FORGOTTEN ISSUE.
Effects of vitamin D on amino acid and polyamine
synthesis41
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VITAMIN D STATUS AND MUSCLE STRENGTH CORRELATE POSITIVELY.
HOWEVER: FURTHER STUDIES ARE NEEDED AND THE MECHANISMS OF ACTION MUST BECOME CLEARER.
Vitamin D and muscle function
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„Vital cell functions: proliferation, differentiation, secretion. Strong autoradiographic binding found in: skin epidermis, hair follicles, sebaceous and sweat glands, myoepthelial cells, certain brain and spinal cord neurons, specific cells in anterior (esp. thyr0tropes) and posterior pituitary, thymus reticular cells, adrenal medullary cells, stomach gland isthmus cells, entero-endocrine cells, pyloric muscle cells, pancreas beta cells, heart atrial myocytes, special cells in salivary glands, all population in female and male reproductive organs, liver sinus littoral cells, perhaps Ito cells. „Stumpf WE. Europ J Drug Metab Pharmacokin 2007, 2008. www:walterstumpf.com
VDRs not found in: „muscle nuclei and fat cells, not at plasma membranes, however found in ground substance of mucosa.“
However: „such negative findings do not exclude possible actions under certain conditions, which point to the merits of further study.“
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Löffler G, Petrides PE. 8th edition, Springer , Germany
The initial health problems due to vitamin D deficiency
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An inhibitory effect of TNF alpha on VDR action results in diminished responsiveness to 1,25(OH)2D3
in osteoporosis and inflammatory arthritis.
„There is now evidence that this effect may be partly mediated by activation of NFkB. Effect not mediated by inhibition of VDR binding to DNA, but by interference with coactivator complexes and polymerase II preinitiator complex.“Farmer PK, et al. Am J Physiol Endocrinol Metab 2000; 279(1):E213-20.
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