Tolerogenic dendritic cells (tDCs) may offer an intervention therapy in autoimmune diseases or transplantation. Stable immaturity and tolerogenic function of tDCs after encountering inflammatory environment are prerequisite for positive outcome of immunotherapy. However, the signaling pathways regulating their stable tolerogenic properties are largely unknown. In this study, we demonstrated that human monocyte-derived tDCs established by using paricalcitol (analogue of vitamin D2), dexamethasone and monophosphoryl lipid A exposed for 24h to LPS, cytokine cocktail, polyI:C or CD40L preserved reduced expression of co-stimulatory molecules, increased levels of inhibitory molecules ILT-3, PDL-1 and TIM-3, increased TLR-2, increased secretion of IL-10 and TGF-β, reduced IL-12 and TNF-α secretion and reduced T cell stimulatory capacity. tDCs further induced IL-10-producing T regulatory cells that suppressed the proliferation of responder T cells. In the inflammatory environment, tDCs maintained up-regulated indoleamine 2, 3 dioxygenase but abrogated IκB-α phosphorylation and reduced transcriptional activity of p65/RelA, RelB and c-Rel NF-κB subunits except p50. Mechanistically, p38 MAPK, ERK1/2, mTOR, STAT3 and mTOR-dependent glycolysis regulated expression of ILT-3, PDL-1 and CD86, secretion of IL-10 and T cell stimulatory capacity of tDCs in the inflammatory environment. Stability of tDCs in the inflammatory environment is thus regulated by multiple signaling pathways.
- Klíčová slova
- Immunology and Microbiology Section, activation pathways, glycolysis, immune response, immunity, immunoregulation, stability, tolerogenic DCs,
- MeSH
- buněčná diferenciace fyziologie MeSH
- dendritické buňky účinky léků metabolismus MeSH
- dexamethason farmakologie MeSH
- ergokalciferoly farmakologie MeSH
- glykolýza účinky léků MeSH
- kultivované buňky MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- NF-kappa B metabolismus MeSH
- signální transdukce MeSH
- TOR serin-threoninkinasy metabolismus MeSH
- transkripční faktor STAT3 metabolismus MeSH
- zánět metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dexamethason MeSH
- ergokalciferoly MeSH
- mitogenem aktivované proteinkinasy MeSH
- MTOR protein, human MeSH Prohlížeč
- NF-kappa B MeSH
- paricalcitol MeSH Prohlížeč
- STAT3 protein, human MeSH Prohlížeč
- TOR serin-threoninkinasy MeSH
- transkripční faktor STAT3 MeSH
OBJECTIVE: This study was designed to evaluate vitamin D status with separate determination of 25-OH D2 and 25-OH D3 and its relationship to vitamin D binding protein (VDBP) in patients with chronic kidney disease (CKD) and long-term haemodialysis patients (HD). METHODS: 45 CKD patients, 103 HD patients, and 25 controls (C) were included. Plasma vitamin D concentrations were determined using chromatography and VDBP in serum and urine in CKD using enzyme immunoassay. RESULTS: Plasma vitamin D levels were lower in CKD (30.16 ± 16.74 ng/mL) and HD (18.85 ± 15.85 ng/mL) versus C (48.72 ± 18.35 ng/mL), P < 0.0001. 25-OH D3 was the dominant form of vitamin D. Serum VDBP was higher in CKD (273.2 ± 93.8 ug/mL) versus C (222 ± 87.6 ug/mL) and HD (213.8 ± 70.9 ug/mL), P = 0.0003. Vitamin D/VDBP ratio was the highest in C and the lowest in HD; however, there was no correlation between vitamin D and VDBP. Urinary concentration of VDBP in CKD (0.25 ± 0.13 ug/mL) correlated with proteinuria (r = 0.43, P = 0.003). CONCLUSIONS: Plasma levels of vitamin D are decreased in CKD patients and especially in HD patients. 25-OH D3 was the major form of vitamin D. Despite urinary losses of VDBP, CKD patients had higher serum VDBP concentrations, indicating compensatory enhanced production. Vitamin D binding protein is not involved in vitamin D deficiency.
- MeSH
- 25-hydroxyvitamin D 2 krev MeSH
- chronická renální insuficience krev komplikace patologie MeSH
- dospělí MeSH
- kalcifediol krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nedostatek vitaminu D krev komplikace patologie MeSH
- protein vázající vitamin D krev MeSH
- senioři MeSH
- vitamin D krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 25-hydroxyvitamin D 2 MeSH
- kalcifediol MeSH
- protein vázající vitamin D MeSH
- vitamin D MeSH
BACKGROUND: Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily. Its ligand, 1,25-(OH)2D, is a metabolically active hormone derived from vitamin D3. The levels of vitamin D3 are decreased in patients with systemic sclerosis (SSc). Here, we aimed to analyse the role of VDR signalling in fibrosis. METHODS: VDR expression was analysed in SSc skin, experimental fibrosis and human fibroblasts. VDR signalling was modulated by siRNA and with the selective agonist paricalcitol. The effects of VDR on Smad signalling were analysed by reporter assays, target gene analyses and coimmunoprecipitation. The effects of paricalcitol were evaluated in the models of bleomycin-induced fibrosis and fibrosis induced by overexpression of a constitutively active transforming growth factor-β (TGF-β) receptor I (TBRI(CA)). RESULTS: VDR expression was decreased in fibroblasts of SSc patients and murine models of SSc in a TGF-β-dependent manner. Knockdown of VDR enhanced the sensitivity of fibroblasts towards TGF-β. In contrast, activation of VDR by paricalcitol reduced the stimulatory effects of TGF-β on fibroblasts and inhibited collagen release and myofibroblast differentiation. Paricalcitol stimulated the formation of complexes between VDR and phosphorylated Smad3 in fibroblasts to inhibit Smad-dependent transcription. Preventive and therapeutic treatment with paricalcitol exerted potent antifibrotic effects and ameliorated bleomycin- as well as TBRI(CA)-induced fibrosis. CONCLUSIONS: We characterise VDR as a negative regulator of TGF-β/Smad signalling. Impaired VDR signalling with reduced expression of VDR and decreased levels of its ligand may thus contribute to hyperactive TGF-β signalling and aberrant fibroblast activation in SSc.
- Klíčová slova
- Fibroblasts, Systemic Sclerosis, Treatment,
- MeSH
- bleomycin toxicita MeSH
- dospělí MeSH
- ergokalciferoly farmakologie MeSH
- fibroblasty účinky léků metabolismus MeSH
- fibróza chemicky indukované metabolismus MeSH
- kůže účinky léků metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- malá interferující RNA metabolismus MeSH
- mladý dospělý MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- proteiny Smad účinky léků metabolismus MeSH
- receptory kalcitriolu agonisté metabolismus MeSH
- senioři MeSH
- signální transdukce účinky léků fyziologie MeSH
- systémová sklerodermie metabolismus MeSH
- transformující růstový faktor beta účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bleomycin MeSH
- ergokalciferoly MeSH
- malá interferující RNA MeSH
- paricalcitol MeSH Prohlížeč
- proteiny Smad MeSH
- receptory kalcitriolu MeSH
- transformující růstový faktor beta MeSH
- VDR protein, human MeSH Prohlížeč
BACKGROUND: Traditionally, secondary hyperparathyroidism (SHPT) due to low calcitriol synthesis in failing kidneys has been treated with synthetic vitamin D receptor (VDR) activators. Recently, also the importance of low native vitamin D status beyond the issue of SHPT has been recognized in these patients. The aim of this work was to evaluate the effect of cholecalciferol supplementation in haemodialysis patients with low vitamin D serum levels. Another aim was to evaluate dual vitamin D therapy (cholecalciferol supplementation plus paricalcitol) in haemodialysis patients with vitamin D deficiency and concomitant SHPT. METHODS: Ninety clinically stable maintenance haemodialysis patients were included. Supervised cholecalciferol supplementation was administered due to low vitamin D status. Patients with SHPT were also treated with synthetic VDR activator. Two pre hoc subgroups for statistical analysis were formed: patients treated solely with cholecalciferol (N=34; 5,000 IU once weekly) and patients treated with a combination of cholecalciferol (identical dose, i.e. 5,000 IU/week) plus paricalcitol (N=34, median dose 10 μg/week). Follow-up visit was scheduled 15 weeks later. Serum concentrations of calcidiol (25-D), parathyroid hormone (PTH) and beta-cross laps (CTX) were assessed at baseline and at follow-up. Serum calcium, phosphate and alkaline phosphatase (ALP) were monitored monthly. Only non-calcium gastrointestinal phosphate binders were administered. Dialysate calcium was 1.5 mmol/L in all patients, and no oral calcium-containing preparations were prescribed. Depending on data distribution, parametric or nonparametric statistical methods were used for comparison within each group (i.e. baseline vs. follow-up data) as well as between groups. RESULTS: In the whole group of 90 patients, mean baseline 25-D serum level was 20.3 (standard deviation 8.7) nmol/L, and it increased to 66.8 (19) nmol/L (p<0.0001) after supplementation. In both preformed subgroups, the effect of vitamin D supplementation was almost identical. In cholecalciferol monotherapy, 25-D levels increased from 18.4 (8.2) to 68.6 (21.2) and in dual vitamin D therapy from 18.4 (5.0) to 67.6 (17.7) nmol/L (both p<0.0001). In addition, both treatment modalities decreased serum PTH levels importantly: from 21.7 (interquartile range 17.3; 35.4) to 18.1 pmol/L (15.3; 24.7) in monotherapy (p=0.05) and from 38.6 (31.8; 53.3) to 33.9 pmol/L (26.1; 47.5) in dual vitamin D therapy (p=0.01). Serum calcium, phosphate, ALP and CTX did not change. We have not observed any episode of hypercalcemia in any subject during the whole period of follow-up. At baseline, slightly lower 25-D levels were observed in diabetic than in non-diabetic patients. This difference disappeared after substitution. Vitamin D status and its changes were not related to the patient's age. CONCLUSION: Low 25-D levels were very common in haemodialysis patients. They were safely and effectively corrected with supervised low-dose cholecalciferol supplementation. In patients with higher baseline PTH levels, dual vitamin D therapy (cholecalciferol plus paricalcitol) was safely and effectively used.
- MeSH
- alkalická fosfatasa krev MeSH
- cholekalciferol aplikace a dávkování MeSH
- chronické selhání ledvin komplikace terapie MeSH
- dialýza ledvin MeSH
- ergokalciferoly terapeutické užití MeSH
- fosfáty krev MeSH
- inhibitory kostní resorpce terapeutické užití MeSH
- kalcifediol krev MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nedostatek vitaminu D krev komplikace farmakoterapie MeSH
- parathormon krev MeSH
- potravní doplňky MeSH
- receptory kalcitriolu agonisté MeSH
- sekundární hyperparatyreóza krev farmakoterapie MeSH
- senioři MeSH
- vápník krev MeSH
- vitaminy aplikace a dávkování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkalická fosfatasa MeSH
- cholekalciferol MeSH
- ergokalciferoly MeSH
- fosfáty MeSH
- inhibitory kostní resorpce MeSH
- kalcifediol MeSH
- parathormon MeSH
- paricalcitol MeSH Prohlížeč
- receptory kalcitriolu MeSH
- vápník MeSH
- vitaminy MeSH
Biomarkers, 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 , are important indicators of the vitamin D general status and are monitored in several pathophysiological disorders, such as osteoporosis, diabetes, heart disease, etc. A novel ultra-HPLC with MS/MS methodology for the analysis of 25-hydroxyvitamin D derivatives coupled with a very simple and highly rapid sample preparation step was developed. Analytical parameters obtained showed linearity (R(2) ) above 0.999 for both vitamins with accuracies between 95.8 and 102%. The LODs were as low as 0.22 and 0.67 nmol/L for 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 , respectively. Intra-assay precision (%RSD) was lower than 4.5%, and inter-assay precision (%RSD) was lower than 6.5%. The feasibility of the developed methodology to be applied in clinical routine analysis has been proved by its application in blood samples from non-agenarian patients, patients with familial hypercholesterolemia and patients suffering from age-related macular degeneration.
- Klíčová slova
- Clinical research, Mass spectrometry, Standard reference material 972, Vitamin D,
- MeSH
- 25-hydroxyvitamin D 2 krev MeSH
- biochemická analýza krve metody MeSH
- časové faktory MeSH
- kalcifediol krev MeSH
- lidé MeSH
- limita detekce MeSH
- referenční standardy MeSH
- tandemová hmotnostní spektrometrie * MeSH
- vysokoúčinná kapalinová chromatografie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
- Názvy látek
- 25-hydroxyvitamin D 2 MeSH
- kalcifediol MeSH
CONTEXT: Low serum 25-hydroxyvitamin D is a risk factor for osteoporosis, cardiovascular disease, diabetes, and cancer. Disruption of noncholesterol sterol absorption due to cholesterol-lowering therapies may result in reduced fat-soluble vitamin absorption. OBJECTIVE: We have previously reported on the cholesterol-lowering efficacy and reduced sterol absorption of probiotic bile salt hydrolase active Lactobacillus reuteri NCIMB 30242; however, the effects on fat-soluble vitamins was previously unknown and the objective of the present study. DESIGN, SETTINGS, PATIENTS, AND INTERVENTION: The study was double-blind, placebo-controlled, randomized, parallel-arm, multicenter lasting 13 weeks. A total of 127 otherwise healthy hypercholesterolemic adults with low-density lipoprotein-cholesterol >3.4 mmol/L, triglycerides <4.0 mmol/L, and body mass index of 22 to 32 kg/m² were included. Subjects were recruited from 6 private practices in Prague, Czech Republic, and randomized to consume L. reuteri NCIMB 30242 or placebo capsules over a 9-week intervention period. OUTCOME MEASURES: The primary outcome measure was the change in serum low-density lipoprotein-cholesterol over the 9-week intervention. Analysis of fat-soluble vitamins at weeks 0 and 9 were performed post hoc. RESULTS: There were no significant differences between L. reuteri NCIMB 30242 and placebo capsule groups in serum vitamin A, vitamin E, or β-carotene or dietary intake over the intervention period (P > .05). L. reuteri NCIMB 30242 increased serum 25-hydroxyvitamin D by 14.9 nmol/L, or 25.5%, over the intervention period, which was a significant mean change relative to placebo of 17.1 nmol/L, or 22.4%, respectively (P = .003). CONCLUSIONS: To our knowledge, this is the first report of increased circulating 25-hydroxyvitamin D in response to oral probiotic supplementation.
- MeSH
- 25-hydroxyvitamin D 2 krev MeSH
- amidohydrolasy škodlivé účinky metabolismus MeSH
- anticholesteremika škodlivé účinky terapeutické užití MeSH
- bakteriální proteiny škodlivé účinky metabolismus MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- hypercholesterolemie krev dietoterapie MeSH
- intestinální absorpce MeSH
- kalcifediol krev MeSH
- LDL-cholesterol krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- Limosilactobacillus reuteri enzymologie metabolismus MeSH
- mladý dospělý MeSH
- nedostatek vitaminu D etiologie prevence a kontrola MeSH
- probiotika škodlivé účinky terapeutické užití MeSH
- senioři MeSH
- vitamin D metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- 25-hydroxyvitamin D 2 MeSH
- amidohydrolasy MeSH
- anticholesteremika MeSH
- bakteriální proteiny MeSH
- choloylglycine hydrolase MeSH Prohlížeč
- kalcifediol MeSH
- LDL-cholesterol MeSH
- vitamin D MeSH
Chronic kidney disease (CKD), and chronic renal failure in particular, is associated with vitamin D deficiency and with a disorder of all metabolic processes that are associated with vitamin D. Calcidiol levels are often low. At present, efforts are made to test and to pharmacologically modulate its levels and thus to contribute to greater availability of the substrate for external calcitriol production. Calcitriol production is reduced in CKD patients not only as a consequence of diminishing functional renal parenchyma but also as a consequence of 1-α-hydroxylase inhibition by FGF-23 and other factors. On the other hand, although parathormone (PTH) increases renal production of calcitriol, it also causes secondary hyperparathyroidism. Synthetic calcitriol (or α-calcidiol) supresses PTH production and is used to treat secondary hyperparathyroidism. This approach is often associated with adverse increase in calcaemia and phosphataemia as the effect on parathyroid glands is associated with an effect on the gastrointestinal tract where calcium and phosphor absorption is increased by calcitriol. Synthetic analogues of vitamin D inhibit parathyroid gland but have significantly lower effect on gastrointestinal tract. Paricalcitol is a selective VDR (vitamin D receptor) activator, used for targeted suppression of parathyroid glands. Vitamin D deficiency in general population is associated, at least in epidemiological studies, with a range of medical complications and the same also applies to patients with renal disease. Although randomised studies are not available, clinical observational studies repeatedly showed treatment with VDR activators to be associated with better prognosis. As other fields of medicine, nephrology currently pays a great attention to vitamin D and vitamin D receptor activation.
- MeSH
- chronická renální insuficience metabolismus MeSH
- chronické selhání ledvin metabolismus MeSH
- ergokalciferoly terapeutické užití MeSH
- fibroblastový růstový faktor 23 MeSH
- kalcitriol metabolismus terapeutické užití MeSH
- lidé MeSH
- protein vázající vitamin D metabolismus MeSH
- receptory kalcitriolu metabolismus MeSH
- sekundární hyperparatyreóza farmakoterapie etiologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ergokalciferoly MeSH
- FGF23 protein, human MeSH Prohlížeč
- fibroblastový růstový faktor 23 MeSH
- kalcitriol MeSH
- paricalcitol MeSH Prohlížeč
- protein vázající vitamin D MeSH
- receptory kalcitriolu MeSH
Vitamin D is the collective name for cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2), which are precursors of hormones with an important role in regulation of the metabolism of calcium and phosphates. This review article describes the production of vitamin D3 in the skin by ultraviolet radiation from sunlight, transport of vitamin D and its metabolites in blood, formation of the active hormonal form - calcitriol (1,25-dihydroxyvitamin D) by hydroxylation in the liver and kidney, and termination of the action by catabolism to inactive metabolites.
- MeSH
- cholekalciferol chemie metabolismus MeSH
- ergokalciferoly chemie metabolismus MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cholekalciferol MeSH
- ergokalciferoly MeSH
Paricalcitol (19-nor-1,25/OH(2)/D(2)), a second generation vitamin D receptor (VDR) activator, is a synthetic analogue of vitamin D3. In contrast to calcitriol, paricalcitol has a reduced effect on intestinal calcium resorption thus avoiding undesirable hypercalcemia. Information about immunomodulatory activity of paricalcitol is scarce. In this study we show that, in all investigated aspects, paricalcitol retains significant immunomodulatory activity, comparable to calcitriol. Both VDR agonists impaired differentiation of immature dendritic cells (DCs) from monocytes. The presence of VDR agonists during DC differentiation abolished their capacity to be activated and, despite potent Toll-like receptor mediated stimulation, VDR agonist-treated DCs remained in the immature state. In accordance with these findings, VDR-treated DCs produced no bioactive IL-12 and had a significantly decreased capacity to induce antigen-specific T cells while the capacity to induce functional Tregs remained unchanged when compared to control DCs. As DCs and T cells play an important role in the pathogenesis of atherosclerosis, in end-stage renal disease patients, paricalcitol should be a VDR agonist of choice for the reduction of the risk of atherosclerosis due to its immunomodulatory effect proven in this study and known limited hypercalcemic effect. The immunomodulatory potency of paricalcitol makes it a drug of interest in the therapy of chronic immune-mediated inflammatory diseases.
- MeSH
- aktivace lymfocytů účinky léků MeSH
- buněčná diferenciace účinky léků imunologie MeSH
- CD8-pozitivní T-lymfocyty účinky léků imunologie MeSH
- dendritické buňky účinky léků imunologie MeSH
- ergokalciferoly farmakologie MeSH
- imunologické faktory farmakologie MeSH
- interleukin-12 biosyntéza imunologie MeSH
- kalcitriol farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- monocyty účinky léků imunologie MeSH
- receptory kalcitriolu agonisté MeSH
- regulační T-lymfocyty účinky léků imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- ergokalciferoly MeSH
- imunologické faktory MeSH
- interleukin-12 MeSH
- kalcitriol MeSH
- paricalcitol MeSH Prohlížeč
- receptory kalcitriolu MeSH
Vitamin D is one of the most important regulating agents in the development of bone mass. Therefore administration of calciferol along with calcium in patients with nutritional vitamin D deficiency leads to improvement of bone density. In patients with osteoporosis who do not respond to vitamin D, insensitivity of osseous tissue to the active metabolite of vitamin D--1,25(OH)2 D3--is involved or inadequate synthesis of active metabolites in the liver or kidneys. Administration of 1alpha-OH vitamin D3 and in particular 1,25(OH) 2D3 improves the general calcium balance in the organism and increases by direct osteoforming action the value of bone mass and improves its quality. Administration of active vitamin D metabolites is unequivocally better in treatment of involutional osteoporosis, either along with calcium or in combination with some antiresorption substance, in osteoporosis associated with chronic inflammatory diseases, after organ transplantation or glukcocorticoid treatment. Even patients with postmenopausal osteoporosis respond better to 1,25(OH)2D3.
- MeSH
- 25-hydroxyvitamin D 2 terapeutické užití MeSH
- ergokalciferoly terapeutické užití MeSH
- kalcitriol terapeutické užití MeSH
- lidé MeSH
- osteoporóza farmakoterapie MeSH
- vitamin D analogy a deriváty terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- 25-hydroxyvitamin D 2 MeSH
- ergokalciferoly MeSH
- kalcitriol MeSH
- vitamin D MeSH