- Impact of vitamin D deficiency on clinical parameters in treatment-naïve rheumatoid arthritis patients. [Journal Article]
- ZRZ Rheumatol 2018 Feb 19
- CONCLUSIONS: A significant association was observed between levels of vitamin D and parameters of disease, including body mass index (BMI), DAS28, Th17 cell counts, Treg cell counts, and presence of anti-CCP antibody in RA patients.
- Mechanisms of Hypercalcemia in Non-Hodgkin Lymphoma and Associated Outcomes: A Retrospective Review. [Journal Article]
- CLClin Lymphoma Myeloma Leuk 2018; 18(2):e123-e129
- CONCLUSIONS: The major mechanism by which NHL patients develop hypercalcemia is not mediated by calcitriol or PTHrP. Hypercalcemia is most prevalent in patients with diffuse large B-cell lymphoma of the nongerminal cell subtype. Patients with calcitriol-mediated hypercalcemia showed a trend toward worse outcomes, suggesting that calcitriol might be a marker of high-grade lymphoma, transformation to such, or a surrogate for more advanced disease.
- Vitamin D receptor expression is essential during retinal vascular development and attenuation of neovascularization by 1, 25(OH)2D3. [Journal Article]
- PlosPLoS One 2017; 12(12):e0190131
- Vitamin D provides a significant benefit to human health, and its deficiency has been linked to a variety of diseases including cancer. Vitamin D exhibits anticancer effects perhaps through inhibitio...
Vitamin D provides a significant benefit to human health, and its deficiency has been linked to a variety of diseases including cancer. Vitamin D exhibits anticancer effects perhaps through inhibition of angiogenesis. We previously showed that the active form of vitamin D (1, 25(OH)2D3; calcitriol) is a potent inhibitor of angiogenesis in mouse model of oxygen-induced ischemic retinopathy (OIR). Many of vitamin D's actions are mediated through vitamin D receptor (VDR). However, the role VDR expression plays in vascular development and inhibition of neovascularization by 1, 25(OH)2D3 remains unknown. Here using wild type (Vdr +/+) and Vdr-deficient (Vdr -/-) mice, we determined the impact of Vdr expression on postnatal development of retinal vasculature and retinal neovascularization during OIR. We observed no significant effect on postnatal retinal vascular development in Vdr -/- mice up to postnatal day 21 (P21) compared with Vdr +/+ mice. However, we observed an increase in density of pericytes (PC) and a decrease in density of endothelial cells (EC) in P42 Vdr -/- mice compared with Vdr +/+ mice, resulting in a significant decrease in the EC/PC ratio. Although we observed no significant impact on vessel obliteration and retinal neovascularization in Vdr -/- mice compared with Vdr +/+ mice during OIR, the VDR expression was essential for inhibition of retinal neovascularization by 1, 25(OH)2D3. In addition, the adverse impact of 1, 25(OH)2D3 treatment on the mouse bodyweight was also dependent on VDR expression. Thus, VDR expression plays a significant role during retinal vascular development, especially during maturation of retinal vasculature by promoting PC quiescence and EC survival, and inhibition of ischemia-mediated retinal neovascularization by 1, 25(OH)2D3.
- Hypercalcaemia preceding diagnosis of Pneumocystis jirovecii pneumonia in renal transplant recipients. [Journal Article]
- CKClin Kidney J 2017; 10(6):845-851
- CONCLUSIONS: Given the outbreak of PJP in our renal transplant cohort, and based on previous experience from other units nationally, we implemented cohort-wide prophylaxis with trimethoprim-sulphamethoxazole for 12 months in consultation with our local infectious diseases unit. Within this period there have been no further local cases of PJP.
- Paclitaxel, Carboplatin and 1,25-D3 Inhibit Proliferation of Endometrial Cancer Cells In Vitro. [Journal Article]
- ARAnticancer Res 2017; 37(12):6575-6581
- CONCLUSIONS: In both cell lines, single-agent paclitaxel was as effective as the combination of the compounds and more effective than single carboplatin. 1,25-D3 may further contribute to the cytotoxic effect of these agents.
- Differential activity of 2-methylene-19-nor vitamin D analogs on growth factor gene expression in rhino mouse skin and comparison to all-trans retinoic acid. [Journal Article]
- PlosPLoS One 2017; 12(11):e0188887
- While all 2-methylene-19-nor analogs of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) tested produce an increase in epidermal thickness in the rhino mouse, only a subset reduce utricle size (comedolysis)....
While all 2-methylene-19-nor analogs of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) tested produce an increase in epidermal thickness in the rhino mouse, only a subset reduce utricle size (comedolysis). All-trans retinoic acid (atRA) also causes epidermal thickening and a reduction in utricle size in the rhino mouse. We now report that 2-methylene-19-nor-(20S)-1α-hydroxybishomopregnacalciferol (2MbisP), a comedolytic analog, increases epidermal thickening more rapidly than does atRA, while both reduce utricle area at an equal rate. Whereas unlike atRA, 2MbisP does not alter the epidermal growth factor receptor ligand, heparin-binding epidermal growth factor-like growth factor, it does increase the expression of both amphiregulin and epigen mRNA, even after a single dose. In situ hybridization reveals an increase in these transcripts throughout the closing utricle as well as in the interfollicular epidermis. The mRNAs for other EGFR ligands including betacellulin and transforming growth factor-α, as well as the epidermal growth factor receptor are largely unaffected by 2MbisP. Another analog, 2-methylene-19-nor-(20S)-26,27-dimethylene-1α,25-dihydroxyvitamin D3 (CAGE-3), produces epidermal thickening but fails to reduce utricle size or increase AREG mRNA levels. CAGE-3 modestly increases epigen mRNA levels, but only after 5 days of dosing. Thus, 2-MbisP produces unique changes in epidermal growth factor receptor ligand mRNAs that may be responsible for both epidermal proliferation and a reduction in utricle size.
- Serum 25-hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 concentrations in adult dogs are more substantially increased by oral supplementation of 25-hydroxyvitamin D3 than by vitamin D3. [Journal Article]
- JNJ Nutr Sci 2017; 6:e30
- We previously found a weak response in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations when dogs were supplemented with oral vitamin D3 (D3). In the present study, we determined the relative pot...
We previously found a weak response in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations when dogs were supplemented with oral vitamin D3 (D3). In the present study, we determined the relative potency of oral 25(OH)D3 compared with D3 for increasing vitamin D status in dogs with low serum 25(OH)D concentrations. Four male and three female, 4-year-old, intact, lean, genetically related, Chinese-crested/beagle dogs were studied in a randomised, single cross-over trial. After feeding a low-vitamin D diet (<4 IU/100 g) for 30 d, four dogs received daily D3 supplementation at 2·3 µg/kg body weight(0·75), while three dogs received a molar equivalency as 25(OH)D3. The supplements, dissolved in ethanol, were applied to a commercial treat for consumption. Serum 25(OH)D3 and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) were analysed weekly using a validated HPLC method. Both supplementations increased (P ≤ 0·01) serum 25(OH)D3 concentrations. However, oral 25(OH)D3 resulted in greater (P < 0·0001) concentrations than D3 by week 1, with a difference of 173 % (P < 0·0001) by week 2. The supplementation period was limited to 14 d after serum 25(OH)D3 concentrations were not appearing to plateau. Thereafter, a washout period of 1 month separated the cross-over. Following 25(OH)D3, but not D3 supplementation, serum 24R,25(OH)2D3 concentrations increased (P ≤ 0·02), 3 to 5 weeks after initiating supplementation. Vitamin D status, as indicated by serum 25(OH)D3 and 24R,25(OH)2D3 concentrations, is more rapidly and efficiently increased in adult dogs by oral supplementation of 25(OH)D3 than D3.
- Endogenous Calcitriol Synthesis Controls the Humoral IgE Response in Mice. [Journal Article]
- JIJ Immunol 2017 Dec 15; 199(12):3952-3958
- The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential ...
The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR. The data show elevated specific IgE and IgG1 concentrations in the blood of OVA-sensitized Cyp27b1-KO mice compared with wild-type littermates (+898 and +219%). Accordingly, more OVA-specific IgG1-secreting cells are present in spleen and fewer in the bone marrow of Cyp27b1-KO mice. Ag-specific mechanisms are suggested as the leucopoiesis is in general unchanged and activated murine B and T lymphocytes express Cyp27b1 Accordingly, elevated specific IgE concentrations in the blood of sensitized T cell-specific Cyp27b1-KO mice support a lymphocyte-driven mechanism. In an independent IgE-inducing model, i.e., intestinal infection with H. polygyrus, we validated the increase of total and specific IgE concentrations of Cyp27b1-KO compared with wild-type mice, but not those of IgG1 or IgA. We conclude that endogenous calcitriol has an impact on the regulation of IgE in vivo. Our data provide genetic evidence supporting previous preclinical and clinical findings and suggest that vitamin D deficiency not only promotes bone diseases but also type I sensitization.
- 1,25-Dihydroxycholecalciferol (calcitriol) modifies uptake and release of 25-hydroxycholecalciferol in skeletal muscle cells in culture. [Journal Article]
- JSJ Steroid Biochem Mol Biol 2017 Oct 26
- The major circulating metabolite of vitamin D3, 25-hydroxycholecalciferol [25(OH)D], has a remarkably long half-life in blood for a (seco)steroid. Data from our studies and others are consistent with...
The major circulating metabolite of vitamin D3, 25-hydroxycholecalciferol [25(OH)D], has a remarkably long half-life in blood for a (seco)steroid. Data from our studies and others are consistent with the hypothesis that there is a role for skeletal muscle in the maintenance of vitamin D status. Muscle cells internalise vitamin D-binding protein (DBP) from the circulation by means of a megalin/cubilin plasma membrane transport mechanism. The internalised DBP molecules then bind to actin and thus provide an intracellular array of high affinity binding sites for its specific ligand, 25(OH)D. There is evidence that the residence time for DBP in muscle cells is short and that it undergoes proteolytic degradation, releasing bound 25(OH)D. The processes of internalisation of DBP and its intracellular residence time, bound to actin, appear to be regulated. To explore whether 1,25-dihydroxycholecalciferol (calcitriol) has any effect on this process, cell cultures of myotubes and primary skeletal muscle fibers were incubated in a medium containing 10-10M calcitriol but with no added DBP. After 3h pre-incubation with calcitriol, the net uptake of 25(OH)D by these calcitriol-treated cells over a further 4h was significantly greater than that in vehicle-treated control cells. This was accompanied by a significant increase in intracellular DBP protein. However, after 16h of pre-incubation with calcitriol, the muscle cells showed a significantly depressed ability to accumulate 25(OH)D compared to control cells over a further 4 or 16hours. These effects of pre-incubation with calcitriol were abolished in fibers from VDR-knockout mice. The effect was also abolished by the addition of 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), which inhibits chloride channel opening. Incubation of C2 myotubes with calcitriol also significantly reduced retention of previously accumulated 25(OH)D after 4 or 8h. It is concluded from these in vitro studies that calcitriol can modify the DBP-dependent uptake and release of 25(OH)D by skeletal muscle cells in a manner that suggests some inducible change in the function of these cells.
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- Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women. [Randomized Controlled Trial]
- AJAm J Clin Nutr 2017; 106(6):1439-1448
- CONCLUSIONS: The numerous associations of many of the placental biomarkers of vitamin D metabolism with circulating vitamin D metabolites among pregnant women [including a CYP27B1-associated increase in 1,25(OH)2D3] and the evidence of trophoblast production and secretion of vitamin D metabolites, especially 25(OH)D3, suggest that the placenta may play an active role in modulating the vitamin D metabolite profile in maternal circulation in human pregnancy. This trial was registered at clinicaltrials.gov as NCT03051867.