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  1. #41
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    Regarding FOS- information from another person(not me):

    Definition:
    https://en.wikipedia.org/wiki/C-Fos

    It is involved in important cellular events, including cell proliferation, differentiation and survival; genes associated with hypoxia; and angiogenesis;[8] which makes its dysregulation an important factor for cancer development. It can also induce a loss of cell polarity and epithelial-mesenchymal transition, leading to invasive and metastatic growth in mammary epithelial cells.[9]

    This one is higly connected with cancer.

    The importance of c-fos in biological context has been determined by eliminating endogenous function by using anti-sense mRNA, anti-c-fos antibodies, a ribozyme that cleaves c-fos mRNA or a dominant negative mutant of c-fos. The transgenic mice thus generated are viable, demonstrating that there are c-fos dependent and independent pathways of cell proliferation, but display a range of tissue-specific developmental defects, including osteoporosis, delayed gametogenesis, lymphopenia and behavioral abnormalities.


    Lack(and probably low level) of c-FOS leads to osteoporosis

    It was found that overexpression of c-fos from class I MHC promoter in transgenic mice leads to the formation of osteosarcomas due to increased proliferation of osteoblasts whereas ectopic expression of the other Jun and Fos proteins does not induce any malignant tumors. Activation of the c-Fos transgene in mice results in overexpression of cyclin D1, A and E in osteoblasts and chondrocytes, both in vitro and in vivo, which might contribute to the uncontrolled growth leading to tumor. Human osteosarcomas analyzed for c-fos expression have given positive results in more than half the cases and c-fos expression has been associated with higher frequency of relapse and poor response to chemotherapy


    Overexpression increase proliferation of osteoblasts

    Several studies have raised the idea that c-Fos may also have tumor-suppressor activity, that it might be able to promote as well as suppress tumorigenesis. Supporting this is the observation that in ovarian carcinomas, loss of c-Fos expression correlates with disease progression. This double action could be enabled by differential protein composition of tumour cells and their environment, for example, dimerisation partners, co-activators and promoter architecture. It is possible that the tumor suppressing activity is due to a proapoptotic function. The exact mechanism by which c-Fos contributes to apoptosis is not clearly understood, but observations in human hepatocellular carcinoma cells indicate that c-Fos is a mediator of c-myc-induced cell death and might induce apoptosis through the p38 MAP kinase pathway. Fas ligand (FASLG or FasL) and the tumour necrosis factor-related apoptosis-inducing ligand (TNFSF10 or TRAIL) might reflect an additional apoptotic mechanism induced by c-Fos, as observed in a human T-cell leukaemia cell line. Another possible mechanism of c-Fos involvement in tumour suppression could be the direct regulation of BRCA1, a well established factor in familial breast and ovarian cancer.


    This can also induce apoptosis by MAP kinase pathaway

    L-type Ca(2+) channel activation regulates induction of c-fos transcription by hypoxia.
    http://www.ncbi.nlm.nih.gov/pubmed/10797155

    In the present study we examined the intracellular pathways that link hypoxia to activation of c-fos gene expression. Experiments were performed on rat pheocromocytoma-12 (PC-12) cells. c-fos mRNA and promoter activities were analyzed by RT-PCR and reporter gene assays, respectively. BAPTA, a Ca(2+) chelator, inhibited c-fos mRNA and promoter activation by hypoxia. Nitrendipine, an L-type Ca(2+)-channel blocker, abolished, whereas BAY K 8644, an L-type channel agonist, enhanced c-fos activation by hypoxia. Ca(2+) currents were augmented reversibly by hypoxia, suggesting that Ca(2+) influx mediated by L-type Ca(2+) channels is essential for c-fos activation by hypoxia. We next determined downstream pathways activated by intracellular Ca(2+) concentration. Immunoblot analysis revealed Ca(2+)/calmodulin-dependent kinase II (CaMKII) protein in PC-12 cells and revealed that hypoxia increased the enzyme activity. KN-93, a CaMK inhibitor, blocked CaMKII activation and c-fos promoter stimulation by hypoxia. Ectopic expression of an active mutant of CaMKII (pCaMKII290) stimulated c-fos promoter activity under normoxia. Hypoxia increased phosphorylation of CREB at the serine residue 133 (Ser-133), and KN-93 attenuated this effect. Point mutations at the Ca(2+)/cAMP-responsive cis-element (Ca/CRE) attenuated, whereas point mutations in the serum-responsive cis-element (SRE) abolished transcriptional activation of c-fos by hypoxia. These results demonstrate that c-fos activation by hypoxia involves CaMK activation and CREB phosphorylation at Ser-133 and requires Ca/CRE and SRE. These observations demonstrate that Ca(2+)-dependent signaling pathways play a crucial role in induction of c-fos gene expression, which may underlie long-term adaptive responses to hypoxia.


    http://www.jbc.org/content/266/12/7876.full.pdf

    The promoter region of the c-fos gene is known to contain
    specific regulatory elements that confer responsiveness to
    phorbol esters and calcium ionophores (24-27). Thus activation
    of protein kinase C and increases in cytosolic [Ca"] are
    both capable of inducing c-fos expression.


    To assess the importance of Ca2+ mobilization resulting from
    mAChR activation, we used the Ca2+ chelator BAPTA to
    buffer the rise in cytosolic [Ca"]. When cells are loaded with
    20 p~ BAPTA for 30 min, carbachol no longer induces an
    increase in cytosolic calcium (37). In BAPTA-loaded cells, the
    mAChR-mediated increase in c-fos mRNA levels is reduced
    by at least 75% (compare lanes 2 and 4, Fig. 5). These data
    suggest that the increase in cytosolic [Ca'+] resulting from
    stimulation of the mAChR is required to maximally induce cfos
    expression.
    In experiments using PMA and ionomycin we confirm that
    both activation of protein kinase C and increases in intracellular
    [Ca'+] are needed to maximally increase c-fos expression.
    Ionomycin at a concentration of 100 nM causes a rapid and
    transient increase in cytosolic [Ca'+] comparable with that
    induced by carbachol (44).


    Increase of intracellular Ca2+ -> increase in c-fos

    Regarding BAPTA- (potential inhibitor of c-fos)

    http://research-repository.uwa...3f7-fb6384dbc8b7).html

    The results confirmed the relationship between EP increase and the fall of scala media CM. One interpretation of these results is that lowering the Ca2+ concentration of endolymph with BAPTA inhibits mechano-electrical transduction in outer hair cells (OHCs) and leaves the hair cell transduction channels in a closed state, thus increasing the resistance across OHCs and increasing the EP.


    It seems that BAPTa is bad for tansduction and...

    Effects of extracellular Ca2+ concentration on hair-bundle stiffness and gating-spring integrity in hair?cells

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC23657/

    When a hair cell is stimulated by positive deflection of its hair bundle, increased tension in gating springs opens transduction channels, permitting cations to enter stereocilia and depolarize the cell. Ca2+ is thought to be required in mechanoelectrical transduction, for exposure of hair bundles to Ca2+ chelators eliminates responsiveness by disrupting tip links, filamentous interstereociliary connections that probably are the gating springs. Ca2+ also participates in adaptation to stimuli by controlling the activity of a molecular motor that sets gating-spring tension. Using a flexible glass fiber to measure hair-bundle stiffness, we investigated the effect of Ca2+ concentration on stiffness before and after the disruption of gating springs. The stiffness of intact hair bundles depended nonmonotonically on the extracellular Ca2+ concentration; the maximal stiffness of ?1200 ?N?m?1 occurred when bundles were bathed in solutions containing 250 ?M Ca2+, approximately the concentration found in frog endolymph. For cells exposed to solutions with sufficient chelator capacity to reduce the Ca2+ concentration below ?100 nM, hair-bundle stiffness fell to ?200 ?N?m?1 and no longer exhibited Ca2+-dependent changes. Because cells so treated lost mechanoelectrical transduction, we attribute the reduction in bundle stiffness to tip-link disruption. The results indicate that gating springs are not linearly elastic; instead, they stiffen with increased strain, which rises with adaptation-motor activity at the physiological extracellular Ca2+ concentration


    and now the bad news

    Intracellular calcium chelator BAPTA protects cells against toxic calcium overload but also alters physiological calcium responses.
    Collatz MB1, Rüdel R, Brinkmeier H.
    Author information
    Abstract
    The effect of the membrane-permeant calcium chelator 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA/AM) on ionomycin-induced cellular calcium overload was studied in single differentiated NH15-CA2 neuroblastoma x glioma hybrid cells. To monitor [Ca2+]i we used the fluorescent indicator Fura-2. Preincubation of the cells with 3 microM BAPTA/AM reduced the number of cells showing deregulation of [Ca2+]i during ionomycin-induced calcium influx. The calcium transients elicited by application of KCl were also severely affected by the chelator. These transients, although varying from cell to cell in shape, amplitude and duration, are well reproducible in individual cells. After incubation of cells for 1 h with 0.3-30 microM BAPTA/AM the time course of these cellular transients was markedly slowed. At 1 microM BAPTA/AM, the time constant of decline of [Ca2+]i was increased by a factor of 4.1 +/- 2.4 (n = 14) and the amplitude was reduced to about 50%. With 30 microM BAPTA/AM, the K(+)-induced calcium transients were almost completely inhibited. We conclude that intracellularly loaded calcium chelators may be used for the prevention of [Ca2+]i-induced cell damage, however, at the expense of a disturbed calcium signalling


    In summary: I have found that BAPTA inhibit c-fos and that Ca2+ induce c-fos, unfotunetely BAPTA disturbe calcium signaling, thus BAPTA is Calcitriol antagonist - it inhibit intracelular Ca2+ :/ I ve also found that Ca2+ is crucial for mechanoelectrical tranduction of hair cells, so this is another + for calcitiol <

    c-FOS(pro-apoptotic protein) is regulated in bald-scalp
    high Ca2(intracellular calcium) levels => c-FOS upregulation

  2. #42
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    there are tons and tons and tons and tons of generic calcitriol easily available everywhere:

    38 pages of generic ORAL calcitirol here in the Indian generics pharmaceuticals industry

    http://www.mims.com/India/drug.../?q=calcitriol&page=0

    YET until the post anecdote linked above from ***alk, we have not head of calcitirol-induced hair regrowth in AGA-individuals anywhere- what does this tells us??

    it proves that the hypothesis about this http://en.wikipedia.org/wiki/Vitamin_D-binding_protein might indeed be the reason why Calcitirol-binded VDR on the balding scalp is downregulated- It's not getting transported to the balding scalp/skull(but is normally expressed else where in the body) in AGA individuals.

    Vitamin D-bind protein:


  3. #43
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    "This is also an interesting video, please note how he talks about injecting vd3 around 12mn into the video. I think topical cream/solution of calcipotriol(http://en.wikipedia.org/wiki/Calcipotriol) can actually reach the derma papilla cell. I am thinking derma roller + calcipotriol, would that work better without inducing hypercalcemia ?
    Really good post Princess! Keep us updated with the results!"

    Calcipotriol
    From Wikipedia, the free encyclopedia
    Calcipotriol
    Calcipotriol.svg
    Systematic (IUPAC) name
    (1R,3S,5E)-5-{2-[(1R,3aS,4Z,7aR)-1-[(2R,3E)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohyytyexane-1,3-diol
    Clinical data
    Trade names Daivobex, Dovobex, Sorilux
    AHFS/Drugs.com monograph
    MedlinePlus a608018
    Pregnancy
    category
    AU: B3
    US: C (Risk not ruled out)
    Legal status
    AU: Prescription Only (S4)
    CA: ?-only
    UK: Prescription-only (POM)
    US: ?-only
    Routes of
    administration Topical
    Pharmacokinetic data
    Bioavailability 5 to 6%
    Metabolism Hepatic
    Excretion Biliary
    Identifiers
    CAS Registry Number 112965-21-6 Yes
    ATC code D05AX02
    PubChem CID: 5288783
    IUPHAR/BPS 2778
    DrugBank DB02300 Yes
    ChemSpider 4450880 Yes
    UNII 143NQ3779B Yes
    KEGG D01125 Yes
    ChEBI CHEBI:50749 Yes
    ChEMBL CHEMBL100918
    Chemical data
    Formula C27H40O3
    Molecular mass 412.605 g/mol
    SMILES[show]
    InChI[show]
    (what is this?) (verify)
    Calcipotriol (INN) or calcipotriene (USAN) is a synthetic derivative of calcitriol, a form of vitamin D. It is used in the treatment of psoriasis, marketed under the trade name "Dovonex" in the United States, "Daivonex" outside of North America, and "Psorcutan" in Germany. This medication is safe for long-term application in psoriatic skin conditions.
    Contents [hide]
    1 Medical uses
    2 Adverse effects
    2.1 Contraindications
    2.2 Interactions
    3 Mechanism
    4 References
    5 External links
    Medical uses[edit]
    Chronic plaque psoriasis is the chief medical use of calcipotriol.[1] It has also been used successfully in the treatment of alopecia areata.[2]

    Adverse effects[edit]
    Adverse effects by frequency:[1][3][4][5]
    Very common (> 10% frequency)
    Burning
    Itchiness
    Skin irritation
    Common (1 - 10% frequency)
    Dermatitis
    Dry skin
    Erythema
    Peeling
    Worsening of psoriasis including facial/scalp
    Rash
    Uncommon (0.1 - 1% frequency)
    Exacerbation of psoriasis
    Rare (< 0.1% frequency)
    Allergic contact dermatitis
    Hypercalcaemia
    Photosensitivity
    Changes in pigmentation
    Skin atrophy

    Mechanism[edit]
    The efficacy of calcipotriol in the treatment of psoriasis was first noticed by the observation of patients receiving various forms of vitamin D in an osteoporosis study. Unexpectedly, some patients who also suffered from psoriasis experienced dramatic reductions in lesion counts.[6]
    The precise mechanism of calcipotriol in remitting psoriasis is not well understood. However, it has been shown to have comparable affinity with calcitriol for the vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism. The vitamin D receptor belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kidney, and T cells of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes.




    Normally, from my own experience of reading up information on experimental meds that might help hairloss- you would expect it's warnings/cautions section to include 'hair loss' as a potential side/adverse effect.

    Surprisingly- Calcipotriol doesnt.

  4. #44
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    ok perhaps this is why ketoconazole makes hair thin and brittle after the initial illusive-thickness-giving effect:

    http://www.ncbi.nlm.nih.gov/pubmed/20870877

    "regulation of the hypoxic response in Candida albicans.
    Synnott JM1, Guida A, Mulhern-Haughey S, Higgins DG, Butler G.
    Author information
    Abstract
    The regulation of the response of Candida albicans to hypoxic (low-oxygen) conditions is poorly understood. We used microarray and other transcriptional analyses to investigate the role of the Upc2 and Bcr1 transcription factors in controlling expression of genes involved in cell wall metabolism, ergosterol synthesis, and glycolysis during adaptation to hypoxia. Hypoxic induction of the ergosterol pathway is mimicked by treatment with sterol-lowering drugs (ketoconazole) and requires UPC2. Expression of three members of the family CFEM (common in several fungal extracellular membranes) of cell wall genes (RBT5, PGA7, and PGA10) is also induced by hypoxia and ketoconazole and requires both UPC2 and BCR1. Expression of glycolytic genes is induced by hypoxia but not by treatment with sterol-lowering drugs, whereas expression of respiratory pathway genes is repressed. However, Upc2 does not play a major role in regulating expression of genes required for central carbon metabolism. Our results indicate that regulation of gene expression in response to hypoxia in C. albicans is complex and is signaled both via lowered sterol levels and other unstudied mechanisms. We also show that induction of filamentation under hypoxic conditions requires the Ras1- and Cdc35-dependent pathway."

    It increases c-fos expression because of high Ca2 levels in balding scalp despite inducing hypoxia- and that leads down the pro-apoptosis pathway instead of the pro-survival pathway

  5. #45
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    From another person(not me)

    Prolonged Expression of c-fos Suppresses Cell Cycle Entry of Dormant Hematopoietic Stem Cells

    http://www.bloodjournal.org/co...3/816?sso-checked=true

    The proto-oncogene c-fos was transiently upregulated in primitive hematopoietic stem (Lin?Sca-1+) cells stimulated with stem cell factor, interleukin-3 (IL-3), and IL-6. To investigate a role of the c-fos in hematopoietic stem cells, we used bone marrow (BM) cells from transgenic mice carrying the c-fos gene under the control of the interferon-?/? - inducible Mx-promoter (Mx - c-fos), and fetal liver cells from c-fos - deficient mice. Prolonged expression of the c-fos in Lin?Sca-1+ BM cells inhibited factor-dependent colony formation and hematopoiesis on a stromal cell layer by keeping them at G0/G1 phase of the cell cycle. These Lin?Sca-1+ BM cells on a stromal layer entered into the cell cycle whenever exogenous c-fos was downregulated. However, ectopic c-fos did not perturb colony formation by Lin?Sca-1+ BM cells after they entered the cell cycle. Furthermore, endogenous c-fos is not essential to cell cycle progression of hematopoietic stem cells because the factor-dependent and the stroma-dependent hematopoiesis by Lin?Sca-1+ fetal liver cells from c-fos - deficient mice was not impaired. These results suggest that the c-fos induced in primitive hematopoietic stem cells negatively controls cell cycle progression and maintains them in a dormant state

    The c-fos proto-oncogene, one of the immediate early genes, is transiently expressed on stimulation by external stimuli leading to cell cycle progression.10 Its product (c-Fos) forms a complex with the product of another proto-oncogene c-jun (AP-1) that regulates expression of AP-1 - binding genes at their transcriptional level.10-12 Thus, c-Fos may play a key role in the transduction of signals induced by external stimuli.12-14 c-Fos is known to be critical for the G0/G1 transition and cell cycle progression in fibroblasts.13 14The overexpression of c-fos in transgenic mice leads to a deregulated bone growth and results in sarcomas,15 16 and the overexpression in several cell lines leads to acceleration of cell cycle progression.17 18 On the contrary, overexpression of c-Fos negatively regulates cell cycle progression in some cell types.19 Thus, functions of c-Fos in cell cycle progression have remained open to question..


    So this one definitely needs to be downregulated. However I was hoping that there wont be a need for that - c-fos is closely connected to cancer and after reading many studies - it should be balanced becouse under and overexpression leads to tumor...

    Because prolonged expression of c-fos inhibits G0/G1 transition of dormant hematopoietic stem cells in both cytokine-dependent (Figs 2 to 5) and stroma-dependent (Fig 8) hematopoiesis, downregulation of the c-fos may initiate G0/G1 transition. Indeed, cell proliferation began in the stem cell culture from Mx - c-fos mice whenever addition of IFN-?/? to the culture was stopped (Fig 8). Therefore, c-Fos may be a gate keeper for cell cycle entry of dormant hematopoietic stem cells.


    In summary, the c-fos was transiently induced in primitive hematopoietic stem cells stimulated with SCF, IL-3, and IL-6. The prolonged expression of c-fos inhibited cell-cycle entry of primitive hematopoietic stem cells stimulated with SCF, IL-3, and IL-6 as well as in case of cultures on a stromal cell layer. Hematopoietic stem cells with the c-fos expression in culture survived in a dormant state and entered the cell cycle after c-fos was downregulated. We propose that c-Fos plays the role of gate keeper in cell cycle progression of dormant hematopoietic stem cells.

  6. #46
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    This is exciting:

    From Dr Cotsarelis's patent:

    Example 2 Suprabasal Bulge Cells, But Not HF Stem Cells, are Depleted in Bald Scalp
    To determine whether destruction of HF stem cells accounted for follicle miniaturization, immuno-histochemical staining was performed on bald scalp with an antibody to KRT15, a marker for follicle stem cells. KRT15(Keratin15- hair follcile progenitor stem cell marker) expression was detected in the miniaturized follicles (FIG. 1C). To determine whether bald scalp exhibited changes in stem cell number, keratinocyte suspensions were stained for KRT15 and FST protein (both intracellularly) and were subjected to flow cytometry to identify bulge follicle stem cells. FST is also a marker for HF stem cells. Cells were also stained for the basal cell marker alpha-6 integrin.

    Cells were effectively permeabilized, as evidenced by the staining of over 90% of cells with antibodies against actin, in contrast to minimal staining from an unrelated isotype antibody (FIG. 2A). A high degree of overlap was observed between KRT15 and FST staining, with comparatively fewer single positive cells (KRT15+/FST? or KRT15?/FST+) than double positive or double negative cells (KRT15+/FST+ or KRT15?/FST?) as shown by the slope of the KRT15 vs. FST plot, which was close to 1 (FIG. 2B). Haired samples from each patient yielded similar results.

    Percentages of HF stem cells in the basal layer of the bulge, defined as KRT15+ or FST+ and alpha-6 integrin+, were similar between haired and bald scalp for all three paired samples (FIG. 2). The percentage of the KRT15+/alpha-6 integrin+ population in the haired and bald scalp was, respectively, 2.12 vs. 2.39 in the 1st patient (FIG. 2C); 2.05 vs. 2.55 in the 2nd patient. Similarly, in the 3rd patient, the percentage of the FST+/alpha-6 integrin+ populations in haired and bald scalp were 1.52% vs. 1.38% (FIG. 2D). Thus, the number of follicular stem cells in bald versus non-bald scalp was essentially constant.

    The KRT15+ and FST+ populations differed between the bald and haired scalp with respect to the distribution of alpha-6 integrin+ cells. Fewer alpha-6 integrin? cells were found in the stem cell compartment of bald scalp. The percentages of the KRT15+/alpha-6 integrin? population were 0.7% and 0.26% in haired and bald scalp, respectively, and the FST+/alpha-6 integrin? population were 0.96% to 0.45%, respectively. Thus the ratio of KRT15+/alpha-6 integrin+ to KRT15+/alpha-6 integrin? increased from 2.17 to 5.3 between haired and bald scalp, and the ratio of FST+/alpha-6 integrin+ to FST+/alpha-6 integrin? cells increased from 2.2 to 5.3. The 3rd subject exhibited a similar 2-fold increase in the ratio of KRT15+/alpha-6 integrin+ to KRT15+/alpha-6 integrin? cells (1.55 vs. 2.97).

    Thus, bald scalp exhibited a relative decrease in the proportion of alpha-6 integrin negative cells within the stem cell compartment.

    And look at this:

  7. #47
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    http://www.ncbi.nlm.nih.gov/pubmed/17199579

    A double-blind, randomized quantitative comparison of calcitriol ointment and calcipotriol ointment on epidermal cell populations, proliferation and differentiation.
    Körver JE1, Vissers WH, van Rens DW, Pasch MC, van Erp PE, Boezeman JB, van De Kerkhof PC.
    Author information
    Abstract
    BACKGROUND:
    Calcitriol and calcipotriol are widely used in the topical treatment of psoriasis. However, studies comparing both treatment modalities are scarce. Especially, there are almost no studies comparing the effects on epidermal cell populations in a quantitative manner.

    OBJECTIVES:
    The aim of this study was to quantitatively compare the effects of topical calcitriol and topical calcipotriol on clinical scores and epidermal subpopulations.

    PATIENTS AND METHODS:
    From five patients with stable plaque psoriasis, skin biopsies were taken from two symmetrical regions on the trunk or extremities before and after treatment with either calcitriol or calcipotriol. Frozen sections were labelled immunofluorescently using direct immunofluorescence for beta-1 integrin and the Zenon labelling technique for keratin (K) 6, K10 and K15. The digital photographs of the stained sections were quantitatively analysed and the results of both treatments were compared.

    RESULTS:
    The clinical SUM-score improved significantly for both the calcitriol- and the calcipotriol-treated lesions. In the calcipotriol-treated group the expression of K10 and K15increased(hair follicle stem cell marker) and the expression of K6 decreased significantly. No changes were seen for the marker beta-1 integrin. In the calcitriol-treated group none of the markers changed significantly. A tendency towards significance was seen for the changes in the expression of K6 and K15 in favour of calcipotriol.

    CONCLUSIONS:
    Both calcitriol and calcipotriol gave a significant improvement in clinical scores. However, treatment with calcipotriol resulted in a normalization of K6, K10 and K15, whereas treatment with calcitriol did not. Comparison of both treatments showed a tendency towards significance for the above-mentioned markers for calcipotriol only.

  8. #48
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    more exciting news:

    http://www.ncbi.nlm.nih.gov/pubmed/17517646

    Vitamin D receptor is essential for normal keratinocyte stem cell function.
    Cianferotti L1, Cox M, Skorija K, Demay MB.
    Author information
    Abstract
    The major physiological role of the vitamin D receptor (VDR) is the maintenance of mineral ion homeostasis. Mutation of the VDR, in humans and mice, results in alopecia. Unlike the effects of the VDR on mineral ion homeostasis, the actions of the VDR that prevent alopecia are ligand-independent. Although absence of the VDR does not prevent the development of a keratinocyte stem cell niche in the bulge region of the hair follicle, it results in an inability of these stem cells to regenerate the lower portion of the hair follicle in vivo and impairs keratinocyte stem cell colony formation in vitro. (CD34 impairment) VDR ablation is associated with a gradual decrease in keratinocyte stem cells, accompanied by an increase in sebaceous activity(sounds familar), a phenotype analogous to that seen with impaired canonical Wnt signaling(familiar also). Transient gene expression assays demonstrate that the cooperative transcriptional effects of beta-catenin and Lef1 are abolished in keratinocytes isolated from VDR-null mice, revealing a role for the unliganded VDR in canonical Wnt signaling. Thus, absence of the VDR impairs canonical Wnt signaling in keratinocytes and leads to the development of alopecia due to a defect in keratinocyte stem cells.

  9. #49
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    "However, by 9 months of age, while CD34 immunoreactivity was preserved in the bulge region of the hair follicles of the wild-type mice (Fig. 3D), it was not present in VDR-null mice"(hair follces becomes 34(-))

    Because these bulge cells make up a small percentage of the keratinocyte population in the skin of mice and are characterized by the expression of both CD34 and A-6 integrin(there u go), cell sorting was performed to address whether the marked impairment of colony formation in the keratinocytes of the 28-day-old VDR-null mice was due to a decrease in the number of KSCs residing in the bulge or a functional abnormality of these cells. Consistent with the normal CD34 immunoreactivity (Fig. 3) of the bulge area in the VDR-null mice at 1 month of age, the number of doubly labeled cells detected by FACS analysis at this age was not significantly altered (Fig. 4A). These data strongly suggest that the KSCs in the VDR-null mice have an altered lineage progression or an altered ability to proliferate (or self-renew or survive) because they are unable to give rise to large stem cell colonies in vitro when placed in culture and are unable to generate functional hair follicles in vivo at a point in time when their numbers are apparently unaffected. It is notable that, with aging, there is a progressive decline in the number of doubly labeled cells in the VDR-null mice due to a marked decrease in CD34-positive cells (Fig. 4 A and C), confirming the lack of CD34 immunoreactivity seen at 9 months of age in the skin of the VDR-null mice (Fig. 3E). These data suggest that KSC self-renewal is impaired by the lack of a functional VDR. To determine whether the lack of VDR expression specifically in the keratinocyte component of the hair follicle is responsible for this reduction in CD34/A-6 integrin-positive cells with age, the KSC number was evaluated in VDR-null mice expressing the K-14 VDR transgene. As indicated in Fig. 4 A and D, the number of doubly labeled KSCs in VDR-null mice expressing the K-14-VDR transgene is not significantly different from that of their wild-type littermates at 1, 3.5, or 9 months of age.

  10. #50
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    Abstract
    BACKGROUND:
    Calcitriol and calcipotriol, two vitamin D derivatives, are available for topical treatment of psoriasis and have been shown to be effective.

    AIM:
    To compare the efficacy and safety of calcitriol 3 microg/g and calcipotriol 50 microg/g.

    METHODS:
    This was a multicentre, randomized, investigator-masked, and parallel comparison in subjects with mild to moderate chronic plaque-type psoriasis receiving either calcitriol or calcipotriol ointment twice daily for 12 weeks. Efficacy evaluations comprised global improvement (on a 4-point scale from 0: no change or worse, to 3: clear or almost clear) assessed by the investigator and by the subject. Efficacy further included the 'dermatological sum score' at each study visit. Safety evaluations included adverse event reporting, cutaneous safety assessed by the investigator and cutaneous discomfort assessment by the subject (both on a 5-point scale from 0: none, to 4: very severe).

    RESULTS:
    A total of 250 subjects of both gender were recruited. At week 12, the LSmean score of global improvement rated by the investigator was 2.27 for calcitriol and 2.22 for calcipotriol. This difference was not statistically significant, with calcitriol demonstrating to be non-inferior to calcipotriol for global improvement. This same parameter was scored by the subject, with a mean of 2.12 for calcitriol and 2.09 for calcipotriol. The percentage of patients with at least marked improvement tended to be in favour of calcitriol (95.7% vs. 85% for calcipotriol). However, differences were not statistically significant. The mean worst score for the cutaneous safety assessment was higher in the calcipotriol group (0.3 vs. 0.1 and 0.4 vs. 0.2, by the investigator and the patient, respectively). These differences were statistically significant in favour of a better safety profile for calcitriol (P=0.0035). Fourteen dermatological and treatment-related adverse events were reported with calcipotriol vs. only five with calcitriol for a total of 22 adverse events reported throughout the study.

    CONCLUSION:
    Calcitriol administered twice daily over a 12-week treatment period demonstrated similar efficacy to calcipotriol, while showing a significantly better safety profile.

    Conclusion = Both are effective with insignificant differences with regards to efficacy- but Calcitriol was better tolerated than Calcipotriol

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