OBJECTIVE: To assess the decrease in serum calcitriol concentrations after hip fracture. METHODS: Serum concentrations of calcitriol, 25(OH)D, parathyroid hormone (PTH), directly measured free 25(OH)D, and indices of bone formation were measured in elderly patients with hip fracture (HF) and patients with elective hip replacement (EHR) at admission and after 7 weeks. RESULTS: A total of 45 patients with HF and 17 patients with EHR completed this prospective study. Baseline serum calcitriol levels were ≤ 60 pmol/l in 26% of the HF patients. After 7 weeks, they significantly decreased (p < 0.001). In patients with EHR, serum calcitriol was within the reference range in all but one patient and did not change during the 7-week recovery phase. Seven weeks after HF, a significant positive relationship was observed between the change in calcitriol and serum 25(OH)D concentration (r = 0.385, p = 0.009) and free 25(OH)D (r = 0.296, p = 0.048), and a decrease in calcitriol during recovery was associated with a decrease in serum PTH (p = 0.038). Seven weeks after HF, changes in both serum PTH and serum 25(OH)D concentrations contributed to the prediction of changes in serum calcitriol (R2 = 0.190, p = 0.012). CONCLUSIONS: Unlike patients with EHR, subjects with HF had low serum 25(OH)D and low free 25(OH)D concentrations at admission, while their serum 1,25D levels were relatively elevated. Decreases in circulating calcitriol levels in the 7 weeks following hip surgery were associated with a resolution of secondary hyperparathyroidism and low availability of free 25(OH)D.

• Klíčová slova
• Calcitriol, Fracture healing, Free 25 hydroxyvitamin D, Hip fracture, Total 25 hydroxyvitamin D,
• MeSH
• fraktury kyčle krev   MeSH
• hojení fraktur fyziologie   MeSH
• kalcitriol krev   MeSH
• lidé MeSH
• náhrada kyčelního kloubu MeSH
• osteogeneze MeSH
• parathormon krev   MeSH
• prospektivní studie MeSH
• referenční hodnoty MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vitamin D analogy a deriváty   krev   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 25-hydroxyvitamin D MeSH Prohlížeč
• kalcitriol MeSH
• parathormon MeSH
• vitamin D MeSH

Thyrotropin (TSH) secretion was assessed in three groups of healthy volunteers before and after four days administration of 1.25(OH)2 vitamin D3 (calcitriol) by the oral route -1.5 micrograms/d (group A), 3.0 micrograms/d (group B) or 3.0 micrograms/d combined with trifluoperazine (8-12 mg/d by mouth) (group C). The control trials and experiments proper were made in the same subjects within one month. The lower calcitriol dose did not change significantly the TRH-stimulated TSH levels nor the secretory reserve measured as the difference of TSH levels at the rest and TRH-stimulated levels (delta TSH) during the 20th, 30th, 40th and 60th minute following TRH administration. A larger calcitriol dose caused a significant increase of TSH values at rest and TRH-stimulated values during the 20th, 30th, 40th and 60th minute following TRH administration (p less than 0.05, p less than 0.05, p less than 0.05, p less than 0.05 and p less than 0.01, respectively) as well as delta TSH (p less than 0.05 at all time intervals). The intracellular calcium antagonist trifluoperazine interfered only with the stimulating effect of calcitriol on the TSH secretion at rest and on delta TSH during the 60th minute following TRH administration, while the TSH levels during the 20th, 30th, 40th and 60th minute after TRH administration were significantly higher, as compared with the control examination (p less than 0.01, p less than 0.01, p less than 0.05 and p less than 0.05, respectively) and also delta TSH was significantly elevated during 20th, 30th, and 40th minute after TRH administration during combined treatment (p less than 0.05, p less than 0.01, p less than 0.05, respectively). Calcitriol thus causes a dose-dependent increase of TSH secretion, probably partly also by a mechanism which is independent on the change of intracellular calcium homeostasis.

• MeSH
• dospělí MeSH
• hormon uvolňující thyreotropin * MeSH
• kalcitriol farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• thyreotropin metabolismus   MeSH
• trifluoperazin farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormon uvolňující thyreotropin * MeSH
• kalcitriol MeSH
• thyreotropin MeSH
• trifluoperazin MeSH

Some epidemiological studies suggested caffeine consumption as the cause for bone mineral density loss. Certain genes involved in this process are regulated by vitamin D receptor (VDR). Therefore, we investigated if caffeine can affect inducible expression of VDR-regulated genes, some of them being involved in bone mineralization process. By employing reporter gene assay, polymerase chain reaction, and western blotting, we monitored the VDR activity and expression in cell cultures of intestinal (LS180), osteosarcoma (HOS), and normal human osteoblasts in vitro. While caffeine stimulated calcitriol-inducible VDR-dependent nanoluciferase activity in stable reporter cell line IZ-VDRE (derived from LS180), it rather modulated mRNA levels of target genes, like CYP24A1, BGLAP, SPP1, and TNSF11 in LS180 and HOS cells. However, caffeine significantly decreased calcitriol-inducible CYP24A1, TNSF11, and SPP1 transcripts in osteoblasts. This decrease had non-linear U-shaped profile. Our in vitro data demonstrate biphasic action of caffeine on the expression of certain calcitriol-inducible VDR-regulated genes in normal human osteoblasts.

• Klíčová slova
• BGLAP, CYP24A1, HOS, IZ-VDRE, Osteoblasts, SPP1,
• MeSH
• kalcitriol farmakologie   MeSH
• kofein farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• osteoblasty účinky léků   metabolismus   MeSH
• osteosarkom farmakoterapie   metabolismus   MeSH
• receptory kalcitriolu účinky léků   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• vitamin D metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kalcitriol MeSH
• kofein MeSH
• receptory kalcitriolu MeSH
• VDR protein, human MeSH Prohlížeč
• vitamin D MeSH

• MeSH
• chronické selhání ledvin komplikace   terapie   MeSH
• dialýza ledvin MeSH
• dihydrotachysterol terapeutické užití   MeSH
• kalcitriol terapeutické užití   MeSH
• lidé MeSH
• nemoci kostí farmakoterapie   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dihydrotachysterol MeSH
• kalcitriol MeSH

The main objective of this study was to analyze changes in the antiproliferative effect of vitamin D3, in the form of calcitriol and calcidiol, via its combined application with all-trans retinoic acid (ATRA) in osteosarcoma cell lines. The response to treatment with calcitriol and calcidiol alone was specific for each cell line. Nevertheless, we observed an enhanced effect of combined treatment with ATRA and calcitriol in the majority of the cell lines. Although the levels of respective nuclear receptors did not correlate with the sensitivity of cells to these drugs, vitamin D receptor (VDR) upregulation induced by ATRA was found in cell lines that were the most sensitive to the combined treatment. In addition, all these cell lines showed high endogenous levels of retinoic acid receptor α (RARα). Our study confirmed that the combination of calcitriol and ATRA can achieve enhanced antiproliferative effects in human osteosarcoma cell lines in vitro. Moreover, we provide the first evidence that ATRA is able to upregulate VDR expression in human osteosarcoma cells. According to our results, the endogenous levels of RARα and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.

• Klíčová slova
• all-trans retinoic acid, calcidiol, calcitriol, osteosarcoma, retinoic acid receptor α, vitamin D receptor,
• MeSH
• alfa receptor kyseliny retinové metabolismus   MeSH
• antitumorózní látky aplikace a dávkování   MeSH
• kalcifediol aplikace a dávkování   MeSH
• kalcitriol aplikace a dávkování   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• osteosarkom farmakoterapie   metabolismus   MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• receptory kalcitriolu metabolismus   MeSH
• tretinoin aplikace a dávkování   MeSH
• vitaminy aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa receptor kyseliny retinové MeSH
• antitumorózní látky MeSH
• kalcifediol MeSH
• kalcitriol MeSH
• receptory kalcitriolu MeSH
• tretinoin MeSH
• vitaminy MeSH

The authors investigated the effects of pharmacological doses of calcitriol (1,25(OH)2-vitamin D3) and trifluoperazine on metabolic and hormonal indicators of glycoregulation in the course of the intravenous glucose tolerance test (IVGTT) in healthy subjects. Calcitriol administered by the oral route for four days, 3 micrograms/d, did not alter the blood sugar and plasma IRI levels at rest nor glucose stimulated values throughout the IVGTT. The slight increase of the glucose assimilation coefficient was not significant, as compared with values of the control test (Kg = (3.9 +/- 0.5) x 10(-2) [min-1] vs. Kg = (3.4 +/- 0.3) x 10(-2) [min-1], respectively). C-peptide plasma levels after calcitriol were slightly higher, significantly during the 14th minute following glucose administration (p less than 0.05), while the two-peak shape of the curve was preserved. Trifluoperazine administered by the oral route for seven days, 10 mg/d, did not significantly affect the blood sugar, IRI and C-peptide values at rest nor glucose induced values throughout the IVGTT nor values of glucose assimilation (Kg = (3.0 +/- 0.4) x 10(-2) [min-1] vs. Kg = (3.4 +/- 0.3) x 10(-2) [min-1] in the control test). In conclusion, neither calcitriol nor trifluoperazine treatment leads to clinically significant alteration of glycoregulation.

• MeSH
• C-peptid krev   MeSH
• dospělí MeSH
• fosfor krev   MeSH
• glukosa aplikace a dávkování   MeSH
• glukózový toleranční test MeSH
• inzulin krev   metabolismus   MeSH
• kalcitriol farmakologie   MeSH
• krevní glukóza analýza   MeSH
• Langerhansovy ostrůvky účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• sekrece inzulinu MeSH
• trifluoperazin farmakologie   MeSH
• vápník krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-peptid MeSH
• fosfor MeSH
• glukosa MeSH
• inzulin MeSH
• kalcitriol MeSH
• krevní glukóza MeSH
• trifluoperazin MeSH
• vápník MeSH

New findings regarding the local synthesis of calcitriol, its binding on nuclear receptors and its regional tissue effects have led to discovery of its endocrine microsystems. Their application in growing organisms and their lifelong functionality provide possible preventive and treatment modalities in multiple ailments, mostly by natural and minimally expensive means.

• MeSH
• kalcitriol nedostatek   fyziologie   MeSH
• lidé MeSH
• nedostatek vitaminu D komplikace   patofyziologie   MeSH
• receptory kalcitriolu fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• kalcitriol MeSH
• receptory kalcitriolu 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

BACKGROUND: Previous research showed that the intracellular complement system, with CD46 as its central molecule, regulates the Th1 response associated with IFN-γ production and transition to a type 1 regulatory response (Tr1) characterized by IL-10 production. This transition can be influenced by a vitamin D (calcitriol), favouring a shift towards Tr1 cells and increased IL-10 production, as described in some autoimmune diseases. OBJECTIVE: It is unknown whether calcitriol modulates CD46-induced Th1 response towards regulatory type 1 T cells (Tr1) in allergic eosinophilic asthma and its value in relation to reducing inflammatory response. METHODS: CD4+ T cells from 58 patients with allergic eosinophilic asthma (AEA) and 49 healthy donors (HDs) were stimulated with αCD3/αCD46/IL-2 or αCD3/αCD46/IL-2/Calcitriol in vitro for 60 h and analyzed by flow cytometry. IFN-γ and IL-10 levels in cell culture supernatants were measured using ELISA. RESULTS: CD4+ T cells from patients with AEA demonstrated elevated CD46 expression in both the non-activated state and under stimulation conditions with αCD3/αCD46/IL-2 or αCD3/αCD46/IL-2/Calcitriol. Moreover, CD46 expression in AEA patients fluctuated with the pollen season, showing a significant increase during period of low pollen exposure. Calcitriol further induced CD4+Tr1 cells from in vitro generated CD4+Th1 cells in both HDs and AEA patients. However, in both cohorts were individuals (HDs: 35/49, AEA: 40/58) who responded to calcitriol with a more pronounced regulatory response. The calcitriol-induced regulatory effect manifested by a stronger surface decrease of CD46 on activated CD4+ T cells (by 40% in HDs and by 26% in AEA), accompanied by a significant inhibition of IFN-γ and increased IL-10 production (by 31% in HDs and by 85% in AEA). These individuals were termed as the CD46D group. Contrary to this, calcitriol induced an increase in CD46 expression at the CD4+ T cell surface in a minor group of HDs (14/49), and AEA patients (18/58), who were termed as the CD46I group. In CD46I group, CD4+ T cells produced less IFN-γ in comparison with CD46D group (by 33% in HDs and by 43% in AEA) and were unable to upregulate IL-10 production following stimulation with αCD3/αCD46/IL-2/Calcitriol. CONCLUSION: Our results suggest the potential existence of a key for stratifying individuals suitable for calcitriol treatment in the context of low serum vitamin D levels. After validation in clinical studies, this key could be used as an adjunctive therapy not only for patients with allergic eosinophilic asthma, but also for other diseases.

• Klíčová slova
• CD46, IFN-γ, IL-10, allergic eosinophilic asthma, calcitriol,
• Publikační typ
• časopisecké články MeSH

In the submitted paper the authors investigated the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol) administered by the oral route for a period of four days in amounts of 3.0 micrograms/d on prolactin secretion at rest and secretion stimulated by thyrotropin-releasing hormone (TRH) and on the lactotrophic secretory reserve assessed as the difference between values at rest and TRH-stimulated prolactin levels during the 20th, 30th, 40th and 60th minute after TRH administration (delta PRL) in 18 healthy women. The untreated control group was formed by 8 healthy women. In the subjects treated with 1,25(OH)2D3 a significant rise of the prolactin levels at rest was recorded and TRH-stimulated values and delta PRL during the 20th and 30th minute after TRH administration significantly increased as compared with control examination, while in the untreated group the values at rest and stimulated prolactin levels and delta PRL did not differ from the values recorded during the control examination. The results confirm the stimulating action of 1,25(OH)2D3 on prolactin secretion in healthy women and indicate a satisfactory reproducibility of TRH test of lactotrophic secretion.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• hormon uvolňující thyreotropin farmakologie   MeSH
• injekce intravenózní MeSH
• kalcitriol aplikace a dávkování   metabolismus   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prolaktin krev   metabolismus   MeSH
• vápník krev   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormon uvolňující thyreotropin MeSH
• kalcitriol MeSH
• prolaktin MeSH
• vápník MeSH