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Vitamin D3 (vitamin + d3)

Distribution by Scientific Domains
Medical Sciences65%
Life Sciences24%
Chemistry8%
Distribution within Medical Sciences
Dermatology27%
Urology9%
Geriatric Medicine6%
12 Other Subdomains58%

Terms modified by Vitamin D3

  • vitamin d3 analogue
    		•
  • vitamin d3 ointment
    		•

    Selected Abstracts

    EFFECT OF VITAMIN D3 ON QUALITY OF LIFE

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2009
    Ghulamullah Shahzad MD
    No abstract is available for this article. [source]

    Two Key Proteins of the Vitamin D Endocrine System Come Into Crystal Clear Focus: Comparison of the X-ray Structures of the Nuclear Receptor for 1,,25(OH)2 Vitamin D3, the Plasma Vitamin D Binding Protein, and Their Ligands,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2003
    Mathew T Mizwicki
    First page of article [source]

    A novel peroxy radical based oxidative stressing system for ranking the oxidizability of drug substances

    JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2006
    Paul A. Harmon
    Abstract A novel oxidative stressing system is described which generates high levels of peroxy radicals in solution at room temperature, without the use of azonitrile initiators. The oxidative stressing system is composed of a 10% solution of Tween 80 in water to which FeCl3,·,6H2O is added. The Tween 80 acts as a solubilizing agent for drug compounds, and also contains substantial amounts of organic hydroperoxides. It is shown that the Fe III/ Fe II couple operates on the hydroperoxide concentration to effectively generate new peroxy radicals, which then propagate in the Tween 80 solution. Key features of the Tween 80/Fe III system are investigated, and the oxidizability of seven known compounds and ten developmental compounds are examined. Relative reaction rates span a 300-fold range, from benzoic acid (nonreactive, defined as <0.5% reacted per day) to Vitamin D3 (7% reacted per hour). Oxidizability "rankings" thus generated are shown to agree well with azonitrile initiated oxidative stress. The potential for general correlations between this type of oxidizability data and actual oxidative performance in LFC and solid oral dosage forms is discussed. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 2014,2028, 2006 [source]

    3D-QSAR Studies on C24-Monoalkylated Vitamin D3 26,23-Lactones and their C2, -Modified Derivatives with Inhibitory Activity to Vitamin D Receptor

    MOLECULAR INFORMATICS, Issue 8-9 2010
    Jinhu Wang
    Abstract The ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) for 82 inhibitors of 25-dehydro-1, -hydroxyvitamin D3 -26,23-lactone analogs has been studied by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. The established CoMFA model in training set gives a cross-validated q2 value of 0.516 and a non-cross-validated rncv2 value of 0.667, while the CoMSIA model results in q2=0.517 and rncv2=0.632. In general, the predictive ability of the CoMFA model is superior to that of the CoMSIA model, with rpred2=0.639 for the CoMFA and rpred2=0.619 for the CoMSIA model. Based on the CoMFA contour maps, some key structural characters of vitamin D3 analogs responsible for inhibitory activity are identified, and some new C2, -modified 24-alkylvitamin D3 lactone analogs with high predicted pIC50 values are designed. The ligand functional group mutations by FEP simulation and docking studies reveal the rationality of the molecular design. [source]

    Prävention und Therapie der Osteoporose.

    PHARMAZIE IN UNSERER ZEIT (PHARMUZ), Issue 3 2009
    Stellenwert von Calcium und Vitamin D
    Eine Monotherapie mit Vitamin D und Calcium ist zur Behandlung der postmenopausalen Osteoporose nicht geeignet. Die Supplementation von Calcium und Vitamin D3 ist aber generell als Basistherapie bei Patienten mit Risikofaktoren und obligat als additive Begleittherapie bei jeder medikamentösen Osteoporosetherapie indiziert und sogar unerlässlich (siehe DVO-Leitlinien). Nach mehrjähriger Behandlung mit effektiven Antiosteoporotika wird oft Calcium plus Vitamin D allein im Sinne einer "Erhaltungstherapie" fortgeführt. Die Datenlage zur fraktursenkenden Wirkung von Calcium und/oder Vitamin D erlaubt folgende Einschätzungen: , Wirkung gesichert: Verminderung von Schenkelhalsfrakturen bei Frauen in Altenheimen mit einem Calcium- und Vitamin-D-Mangel durch die kombinierte Gabe von Vitamin D plus Calcium. , Wirkung wahrscheinlich: Verminderung von peripheren Frakturen bei Frauen und Männern im höheren Lebensalter mit Calcium- und Vitamin-D-Mangel durch die kombinierte Gabe von Vitamin D plus Calcium. , Wirkung möglich: Verminderung von peripheren Frakturen und Wirbelkörperfrakturen bei Männern und Frauen in allen Altersklassen durch eine Optimierung der Calcium- und Vitamin-D-Versorgung. Bei älteren Menschen muss die Vitamin-D-Gabe wegen der mangelhaften Produktion in der Haut Sommer wie Winter erfolgen. Die Serumkonzentration an 25-Hydroxyvitamin D sollte mindestens 20 ng/mL und durchschnittlich 30 ng/mL betragen. Um diesen Spiegel zu erreichen, ist eine tägliche Aufnahme von ca. 800 IE (20 ,g) Vitamin D erforderlich. Eine Vitamin-D- und Calcium-Zufuhr ist insbesondere in der Schwangerschaft und Stillzeit angezeigt. Wir empfehlen in unserer Ambulanz zur Prävention der Therapie der Osteoporose als Basistherapie die "1000er Regel": täglich 1000 mg Calcium und 1000 IE Vitamin D3. Vitamin D reduziert ferner das Sturzrisiko, verbessert die Muskelkraft und besitzt noch zahlreiche positive Wirkungen auf andere Organsysteme. Das Auftreten von Nierensteinen oder einer Gefäßverkalkung ist bei Osteoporose-Patienten in der empfohlenen Dosis und bei normaler Flüssigkeitszufuhr nicht zu befürchten. Der Einsatz aktiver Vitamin-D-Metabolite ist auf Grund der Studiendatenlage zur Therapie der postmenopausalen Osteoporose nicht zu empfehlen und nur bei Funktionsstörungen der Leber und/oder Niere zu diskutieren. Ein unkritischer Einsatz von hydroxylierten Formen des Vitamin D bei Sturzpatienten ist auch aus Kostengründen nicht sinnvoll. Eine Substitution mit anderen Mineralien, Vitaminen oder Spurenelementen ist nur bei Vorliegen von nachgewiesenen Mangelzuständen sinnvoll und vertretbar. [source]

    Vitamin D3 upregulated protein 1 (VDUP1) is a regulator for redox signaling and stress-mediated diseases

    THE JOURNAL OF DERMATOLOGY, Issue 10 2006
    Jin Woong CHUNG
    ABSTRACT Vitamin D3 upregulated protein 1 (VDUP1) is a 46-kDa multifunctional protein, initially isolated in HL-60 cells as a protein of which expression is upregulated by vitamin D3 administration. Subsequently, it was identified independently by investigators from diverse scientific backgrounds as a thioredoxin binding protein that negatively regulates the expression and the activity of thioredoxin, and is thus involved in redox regulation. Further studies have revealed that VDUP1 plays multiple roles in a wide range of cellular processes such as proliferation or apoptosis. Recently, it has been reported that VDUP1 is also involved in the immune system via positive regulation of natural killer development. In addition, VDUP1 has been revealed to be associated with the fatty acid utilization. In the present review, we discuss the novel aspects of VDUP1 function as well as the historical background of VDUP1. Future studies will explore the diagnostic and therapeutic potential of modulating the function of VDUP1 in vivo. [source]

    Percent true calcium absorption, mineral metabolism, and bone mass in children with arthritis: Effect of supplementation with vitamin D3 and calcium,,

    ARTHRITIS & RHEUMATISM, Issue 10 2008
    Laura S. Hillman
    Objective To assess whether percent true calcium absorption (,) is normal and whether supplementation with placebo, vitamin D3 (2,000 IU/day), calcium (1,000 mg/day), or vitamin D3 plus calcium improves ,, mineral metabolism, or bone mass accrual in children with arthritis. Methods Eighteen children received all 4 treatments, each for 6 months, in 4 different, randomly assigned orders. Changes in levels of 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D), parathyroid hormone, bone turnover markers, and minerals and in bone mineral content were measured. Calcium absorption was determined with a dual stable isotope method using 48Ca administered intravenously and 46Ca administered orally, and measuring 48Ca, 46Ca, and 42Ca in a 24-hour urine specimen by high-resolution inductively coupled plasma mass spectroscopy. Wilcoxon's signed rank test was used both to identify significant change over the treatment period with a given regimen and to compare change with an experimental treatment versus change with placebo. Results Percent true calcium absorption was in the lower-normal range and did not differ by treatment (mean ± SD 28.3 ± 20.2% with placebo, 26.1 ± 12.1% with calcium, 19.2 ± 11.7% with vitamin D3, and 27.1 ± 16.5% with vitamin D3 plus calcium). With vitamin D3 and vitamin D3 plus calcium treatment, 25(OH)D levels were increased and 1,25(OH)2D levels were maintained. Serum calcium levels were increased only with vitamin D3 and vitamin D3 plus calcium treatment. Levels of bone turnover markers and increases in bone mineral content did not differ by treatment. Conclusion The findings of this study indicate that percent true calcium absorption is low-normal in children with arthritis. Vitamin D3 at 2,000 IU/day increases serum 25(OH)D and calcium levels but does not improve bone mass accretion. Calcium at 1,000 mg/day also failed to improve bone mass. [source]

    The Effect of Oxcarbazepine on Bone Metabolism

    ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2009
    Y. Çetinkaya
    Objective,,, Long term use of several antiepileptic drugs is known to cause alteration in bone metabolism. Therefore, we investigated the effect of new antiepileptic drug, oxcarbazepine, on bone metabolism. Methods,,, Twenty eight patients who were on oxcarbazepin therapy (18 female, 10 males; mean age: 27.82 ± 10.98 years (range: 15,45)) with no additional antiepileptic drug use history in one year period prior to the study and 28 control subjects were involved in the study. Measurement of calcium, phosphate, alkaline phosphatase and Vitamin D3 levels and bone density measurements with DEXA method were performed in patient and age-matched control groups. The baseline parameters were compared with the control group and with those measured at the end of one year. Results,,, The biochemical (calcium, phosphate, alkaline phosphatase and Vitamin D3) parameters and densitometry values after one year of therapy were not different than the baseline values indicating that those were not affected by the therapy (P > 0.05). Conclusions,,, In previous studies, anticonvulsant drugs that induce enzymes increase bone degradation by causing vitamin D deficiency. According to the results of this study, oxcarbazepin with little effect on enzyme induction was shown not to affect bone mineral metabolism. [source]

    Innate immunity to mycobacteria: vitamin D and autophagy

    CELLULAR MICROBIOLOGY, Issue 8 2010
    Eun-Kyeong Jo
    Summary Autophagy is an ancient mechanism of protein degradation and a novel antimicrobial strategy. With respect to host defences against mycobacteria, autophagy plays a crucial role in antimycobacterial resistance, and contributes to immune surveillance of intracellular pathogens and vaccine efficacy. Vitamin D3 contributes to host immune responses against Mycobacterium tuberculosis through LL-37/hCAP-18, which is the only cathelicidin identified to date in humans. In this review, we discuss recent advances in our understanding of host immune strategies against mycobacteria, including vitamin D-mediated innate immunity and autophagy activation. This review also addresses our current understanding regarding the autophagy connection to principal innate machinery, such as ubiquitin- or inflammasome-involved pathways. Integrated dialog between autophagy and innate immunity may contribute to adequate host immune defences against mycobacterial infection. [source]

    Prospective screening for biopsy proven coeliac disease, autoimmunity and malabsorption markers in Belgian subjects with Type 1 diabetes

    DIABETIC MEDICINE, Issue 7 2005
    M. Buysschaert
    Abstract Aims To determine prospectively the prevalence of biopsy proven coeliac disease (CD) in an adult Type 1 diabetic population from Belgium with regards to associated auto-immunity and malabsorption. Methods and results Determination in 400 Type 1 diabetic patients of serum anti-endomysial and/or anti-transglutaminase auto-antibodies. All subjects with abnormal serology underwent an intestinal biopsy. Ten patients (2.5%) had positive antibodies. Diagnosis of CD was confirmed by an intestinal biopsy. Eight patients were symptom-free, although laboratory findings suggesting malabsorption were prominent in the presence of CD [microcytic anaemia, iron and folate deficiencies, low levels of 25(OH)vitamin D3, calcium and cholesterol]. Other auto-immune conditions, especially vitiligo, were found in patients with CD. Conclusions Asymptomatic coeliac disease occurs frequently in adult Type 1 diabetic patients, and is often associated with subclinical malabsorption. Screening should be part of routine evaluation, to implement life-long dietary gluten avoidance. [source]

    Sweat gland epithelial and myoepithelial cells are vitamin D targets

    EXPERIMENTAL DERMATOLOGY, Issue 2 2007
    Nobuo Koike
    Abstract:, Nuclear receptor binding of 1,25(OH)2 -vitamin D3 (vitamin D) in skin keratinocytes of epidermis, hair sheaths and sebaceous glands was discovered through receptor microscopic autoradiography. Extended experiments with 3H-1,25(OH)2 -vitamin D3 and its analog 3H-oxacalcitriol (OCT) now demonstrate nuclear receptor binding in sweat gland epithelium of secretory coils and ducts as well as in myoepithelial cells, as studied in paws of nude mice after i.v. injection. The results suggest genomic regulation of cell proliferation and differentiation, as well as of secretory and excretory functions, indicating potential therapies for impaired secretion as in hypohidrosis of aged and diseased skin. [source]

    Vitamin D and skin: new aspects for dermatology

    EXPERIMENTAL DERMATOLOGY, Issue 2004
    Bodo Lehmann
    Abstract:, It has been shown that epidermal keratinocytes have the capacity for the UVB-induced photochemical conversion of 7-dehydrocholesterol to vitamin D3, and also for the enzymatically controlled hydroxylation of the photolysis product. This metabolic loop results in the formation of the biologically active final product 1,,25-dihydroxyvitamin D3 (1,,25(OH)2D3, calcitriol). The epidermal synthesis of calcitriol is of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and immunocompetent cells. Because of their anti-proliferative and prodifferentiating effects, calcitriol and other vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. In addition, the known therapeutic effect of UVB light therapy in the treatment of psoriasis may, at least in part, be mediated via UVB-induced synthesis of calcitriol. Increasing evidence now indicates that cutaneous vitamin D synthesis is of great importance for the prevention of a broad variety of diseases, including various malignancies. It has been postulated that cancer mortality could be reduced via careful UV exposure or, more safely, via oral substitution with vitamin D. These new findings must be taken into account when establishing new sun protection guidelines for the prevention of skin cancer. In addition, better understanding of the metabolism of vitamin D in the skin has opened up new perspectives for the therapeutic application of vitamin D analogs, e.g. in inflammatory skin diseases. [source]

    Conversion of vitamin D3 to 1,,25-dihydroxyvitamin D3 in human skin equivalents

    EXPERIMENTAL DERMATOLOGY, Issue 2 2000
    B. Lehmann
    Abstract: These results demonstrate for the first time that human keratinocytes under in vivo -like conditions have the capacity of the enzymatic hydroxylation of vitamin D3 to hormonally active calcitriol (1,,25(OH)2D3). Supplementation of the culture medium with bovine serum albumin (BSA) up to 1.5% (w/v) amplifies the conversion of vitamin D3 to 1,,25(OH)2D3. The maximum turnover rate of this reaction at 780 nM vitamin D3 in presence of 1.0% (w/v) BSA amounts to approximately 3 pmol 1,,25(OH)2D3 per 106 cells after 6 h of incubation. The hydroxylation of vitamin D3 to 1,,25(OH)2D3 is inhibited by the P-450 oxidase inhibitor ketoconazole. The generation of 1,,25(OH)2D3 from vitamin D3 has an apparent Michaelis constant (Km) of 2.3×10,6 M. The intrinsic conversion of vitamin D3 to biologically active 1,,25(OH)2D3 may be of importance for the regulation of proliferation and differentiation of keratinocytes. [source]

    Elderly patient presenting with severe thyrotoxic hypercalcemia

    GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2006
    Reiko Kikuchi
    An 81-year-old woman with Graves' disease and osteoporosis was referred to the hospital because of anorexia over one month and impaired consciousness. She also presented with low-grade fever and emaciation. Laboratory tests revealed marked hypercalcemia (corrected serum calcium level of 12.4 mg/dL), which was initially suspected to result from vitamin D toxicity, because she had been taking vitamin D3 (alphacalcidol of 0.5 µg/day) for the treatment of osteoporosis. However, discontinuation of vitamin D3 and fluid infusion did not ameliorate hypercalcemia one week later. After excluding hyperparathyroidism and malignancy-related hypercalcemia, hypercalcemia was considered to be attributable to the exacerbation of hyperthyroidism (free T4 of 6.69 ng/dL, free T3 of 13.27 pg/mL and thyroid stimulating hormone (TSH) <0.015 µIU/mL) with increased bone resorption. Finally, the increased dose of thiamazole (30 mg/day) normalized serum calcium level and thyroid function three months later. Laboratory tests suggested that normal bone formation in spite of increased bone resorption contributed to hypercalcemia in hyperthyroid state. [source]

    Effect of 1,,25-dihydroxyvitamin D3 in embryonic hippocampal cells

    HIPPOCAMPUS, Issue 6 2010
    Francesca Marini
    Abstract Although the role of 1,,25-dihydroxyvitamin D3 in calcium homeostasis of bone tissue is clear, evidence of the involvement of vitamin D3 in the central nervous system functions is increasing. In fact, vitamin D3 regulates vitamin D receptor and nerve growth factor expression, modulates brain development, and reverses experimental autoimmune encephalomyelitis. Only few studies, however, address vitamin D3 effect on embryonic hippocampal cell differentiation. In this investigation, the HN9.10e cell line was used as experimental model; these cells, that are a somatic fusion product of hippocampal cells from embryonic day-18 C57BL/6 mice and N18TG2 neuroblastoma cells, show morphological and cytoskeletal features similar to their neuronal precursors. By this model, we have studied the time course of vitamin D3 localization in the nucleus and its effect on proteins involved in proliferation and/or differentiation. We found that the translocation of vitamin D3 from cytoplasm to the nucleus is transient, as the maximal nuclear concentration is reached after 10 h of incubation with 3H-vitamin D3 and decreases to control values by 12 h. The appearance of differentiation markers such as Bcl2, NGF, STAT3, and the decrease of proliferation markers such as cyclin-1 and PCNA are late events. Moreover, physiological concentrations of vitamin D3 delay cell proliferation and induce cell differentiation of embryonic cells characterized by modification of soma lengthening and formation of axons and dendrites. © 2009 Wiley-Liss, Inc. [source]

    Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2007
    Naohiko Okamoto
    Objective: Although hypercalciuria, a well-established adverse effect of vitamin D3, can be a risk factor of renal stone formation, the risk of nephrolithiasis has not been well defined. The consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones. In the present study, we investigated the effect of chronic acid ingestion on kidney stone formation in rats treated with calcitriol (1,25[OH]2 D3). Methods: Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 µg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 µg of calcitriol per week) rats (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone samples were analyzed. Results: The A-V rats exhibited elevated serum calcium concentrations, urinary calcium and phosphate excretion, urinary type I collagen cross-linked N-peptide (NTx)/creatinine values, mRNA expression of osteopontin in the kidney, and renal calcium contents as well as decreased bone mineral densities, compared with the C-C and C-V rats. Urinary citrate excretion was lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats. Conclusions: The ingestion of NH4Cl, an acid precursor, promotes calcium phosphate kidney stone formation in calcitriol-treated rats. The chronic intake of a diet rich in acid precursors may be a risk factor for the development of kidney stones in subjects who are being treated with calcitriol. [source]

    Murine and Chicken Chondrocytes Regulate Osteoclastogenesis by Producing RANKL in Response to BMP2,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2008
    Michihiko Usui
    Abstract Chondrocytes express RANKL, but their role in osteoclastogenesis is not clear. We report that hypertrophic chondrocytes induce osteoclast formation through RANKL production stimulated by BMP2 and Runx2/Smad1 and thus they may regulate resorption of calcified matrix by osteoclasts at growth plates. Introduction: Bone morphogenetic protein (BMP) signaling and Runx2 regulate chondrogenesis during bone development and fracture repair and RANKL expression by osteoblast/stromal cells. Chondrocytes express RANKL, and this expression is stimulated by vitamin D3, but it is not known if chondrocytes directly support osteoclast formation or if BMPs or Runx2 is involved in this potential regulation of osteoclastogenesis. Material and Methods: The chondrocyte cell line, ATDC5, primary mouse sternal chondrocytes, and chick sternal chondrocytes were used. Cells were treated with BMP2, and expression of RANKL and chondrocyte marker genes was determined by real-time RT-PCR and Western blot. Chondrocytes and spleen-derived osteoclast precursors ± BMP2 were co-cultured to examine the effect of chondrocyte-produced RANKL on osteoclast formation. A reporter assay was used to determine whether BMP2-induced RANKL production is through transcriptional regulation of the RANKL promoter and whether it is mediated by Runx2. Results: BMP2 significantly increased expression of RANKL mRNA and protein in all three types of chondrocytes, particularly by Col X-expressing and upper sternal chondrocytes. Chondrocytes constitutively induced osteoclast formation. This effect was increased significantly by BMP2 and prevented by RANK:Fc. BMP2 significantly increased luciferase activity of the RANKL-luc reporter, and Smad1 increased this effect. Deletion or mutation of Runx2 binding sites within the RANKL promoter or overexpression of a dominant negative Runx2 abolished BMP2- and Smad1-mediated activation of RANKL promoter activity. Conclusions: Hypertrophic chondrocytes may regulate osteoclastogenesis at growth plates to remove calcified matrix through BMP-induced RANKL expression. [source]

    CYP3A4 is a Human Microsomal Vitamin D 25-Hydroxylase,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004
    Ram P Gupta
    Abstract The human hepatic microsomal vitamin D 25-hydroxylase protein and gene have not been identified with certainty. Sixteen hepatic recombinant microsomal enzymes were screened for 25-hydroxylase activity; 11 had some 25-hydroxylase activity, but CYP3A4 had the highest activity. In characterized liver microsomes, 25-hydroxylase activity correlated significantly with CYP3A4 testosterone 6,-hydroxylase activity. Activity in pooled liver microsomes was inhibited by known inhibitors of CYP3A4 and by an antibody to CYP3A2. Thus, CYP3A4 is a hepatic microsomal vitamin D 25-hydroxylase. Introduction: Studies were performed to identify human microsomal vitamin D-25 hydroxylase. Materials and Methods: Sixteen major hepatic microsomal recombinant enzymes derived from cytochrome P450 cDNAs expressed in baculovirus-infected insect cells were screened for 25-hydroxylase activity with 1,-hydroxyvitamin D2 [1,(OH)D2], 1,-hydroxyvitamin D3 [1,(OH)D3], vitamin D2, and vitamin D3 as substrates. Activity was correlated with known biological activities of enzymes in a panel of 12 characterized human liver microsomes. The effects of known inhibitors and specific antibodies on activity also were determined. Results: CYP3A4, the most abundant cytochrome P450 enzyme in human liver and intestine, had 7-fold greater activity than that of any of the other enzymes with 1,(OH)D2 as substrate. CYP3A4 25-hydroxylase activity was four times higher with 1,(OH)D2 than with 1,(OH)D3 as substrate, was much less with vitamin D2, and was not detected with vitamin D3. 1,(OH)D2 was the substrate in subsequent experiments. In a panel of characterized human liver microsomes, 25-hydroxylase activity correlated with CYP3A4 testosterone 6,-hydroxylase activity (r = 0.93, p < 0.001) and CYP2C91 diclofenac 4,-hydroxylase activity (r = 0.65, p < 0.05), but not with activity of any of the other enzymes. Activity in recombinant CYP3A4 and pooled liver microsomes was dose-dependently inhibited by ketoconazole, troleandomycin, isoniazid, and ,-naphthoflavone, known inhibitors of CYP3A4. Activity in pooled liver microsomes was inhibited by antibodies to CYP3A2 that are known to inhibit CYP3A4 activity. Conclusion: CYP3A4 is a vitamin D 25-hydroxylase for vitamin D2 in human hepatic microsomes and hydroxylates both 1,(OH)D2 and 1,(OH)D3. [source]

    The classic receptor for 1,,25-dihydroxy vitamin D3 is required for non-genomic actions of 1,,25-dihydroxy vitamin D3 in osteosarcoma cells

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2006
    Soraya Bravo
    Abstract 1,,25-dihydroxy vitamin D3 has a major role in the regulation of the bone metabolism as it promotes the expression of key bone-related proteins in osteoblastic cells. In recent years it has become increasingly evident that in addition to its well-established genomic actions, 1,,25-dihydroxy vitamin D3 induces non-genomic responses by acting through a specific plasma membrane-associated receptor. Results from several groups suggest that the classical nuclear 1,,25-dihydroxy vitamin D3 receptor (VDR) is also responsible for these non-genomic actions of 1,,25-dihydroxy vitamin D3. Here, we have used siRNA to suppress the expression of VDR in osteoblastic cells and assessed the role of VDR in the non-genomic response to 1,,25-dihydroxy vitamin D3. We report that expression of the classic VDR in osteoblasts is required to generate a rapid 1,,25-dihydroxy vitamin D3-mediated increase in the intracellular Ca2+ concentration, a hallmark of the non-genomic actions of 1,,25-dihydroxy vitamin D3 in these cells. J. Cell. Biochem. 99: 995,1000, 2006. © 2006 Wiley-Liss, Inc. [source]

    1,25(OH)2 -vitamin D3 induces translocation of the vitamin D receptor (VDR) to the plasma membrane in skeletal muscle cells

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2002
    Daniela Capiati
    Abstract 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3), the hormonally active form of vitamin D3, acts through two different mechanisms. In addition to regulating gene expression via the specific intracellular vitamin D receptor (VDR), 1,25(OH)2D3 induces rapid, non-transcriptional responses involving stimulation of transmembrane signal transduction pathways. The activation of second messengers supports the hypothesis that a membrane-bound steroid receptor similar to those that mediate peptide hormone biology exists. Skeletal muscle is a target tissue for 1,25(OH)2D3. Avian embryonic skeletal muscle cells (myoblasts/myotubes) have been shown to respond both genomically and non-genomically to the hormone. The present study provides evidence indicating that short-term treatment (1,10 min) with 1,25(OH)2D3 induces translocation of the VDR from the nuclear to the microsomal fraction in chick myoblasts. This translocation is blocked by colchicine, genistein, or herbimycin, suggesting the involvement of microtubular transport and tyrosine kinase/s in the relocation of the receptor. By isolation of plasma membranes, it was demonstrated that the hormone increases the amounts of VDR specifically in this fraction. These results suggest that the nuclear VDR may be the receptor that mediates the non-genomic effects of 1,25(OH)2D3 in chick myoblasts. J. Cell. Biochem. 86: 128,135, 2002. © 2002 Wiley-Liss, Inc. [source]

    Autocrine TGF, signaling mediates vitamin D3 analog-induced growth inhibition in breast cells

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2001
    Limin Yang
    In this study, we address whether TGF, signaling mediates vitamin D3 analog-induced growth inhibition in nonmalignant and malignant breast cells. Normal mammary epithelial cells (184), immortalized nonmalignant mammary epithelial cells (184A1 and MCF10A), and breast cancer cells (early passage MCF7: MCF7E) were sensitive to the inhibitory effects of vitamin D3 analogs (EB1089 and MC1288) while late passage MCF7 breast cancer (MCF7L) cells were relatively resistant. A similar pattern of sensitivity to TGF, was observed with these cells. Thus, the sensitivity to the vitamin D3 analogs correlated with the sensitivity to TGF,. MCF7L TGF,RII-transfected cells, which have autocrine TGF, activity, were more sensitive to EB1089 than MCF7L cells. TGF, neutralizing antibody was found to block the inhibitory effects of these analogs. These results are consistent with the idea that autocrine TGF, signaling mediates the anti-proliferative effects of the vitamin D3 analogs in these cells. The expression of TGF, isoforms and/or TGF, receptors was induced by the analogs in the vitamin D3 and TGF, sensitive cells. Vitamin D3 analogs did not induce TGF, or TGF, receptor expression in the resistant MCF7L cells. Therefore, EB1089 induces autocrine TGF, activity through increasing expression of TGF, isoforms and/or TGF, receptors. In addition, EB1089 induced nuclear VDR protein levels in the sensitive 184A1 cells but not in the resistant MCF7L cells. 184A1 cells were more sensitive to EB1089-induced VDR-dependent transactivation than MCF7L cells as measured by a luciferase reporter construct containing the VDRE, indicating a defect of VDR signaling in MCF7L cells. Smad3, a TGF, signaling mediator, coactivated VDR-dependent transactivation in 184A1 cells but not in MCF7L cells. These results indicate that Smad3 coactivates VDR to further enhance TGF, signaling and vitamin D3 signaling in the sensitive 184A1 cells. The results also indicate that Smad3 is not of itself sufficient to coactivate VDR in TGF,/vitamin D3 resistant MCF7L cells and other factors are required. We found that the PI 3-kinase pathway inhibitor LY29004 inhibited the synergy of TGF, and EB1089 on VDR-dependent transactivation activity. This indicates that the crosstalk between TGF, and vitamin D signaling is also PI 3-kinase pathway dependent. © 2001 Wiley-Liss, Inc. [source]

    Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF)

    JOURNAL OF MEDICAL VIROLOGY, Issue 1 2009
    Nobuto Yamamoto
    Abstract Serum Gc protein (known as vitamin D3 -binding protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of HIV-infected patients was lost or reduced because Gc protein is deglycosylated by ,- N -acetylgalactosaminidase (Nagalase) secreted from HIV-infected cells. Therefore, macrophages of HIV-infected patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Since Nagalase is the intrinsic component of the envelope protein gp120, serum Nagalase activity is the sum of enzyme activities carried by both HIV virions and envelope proteins. These Nagalase carriers were already complexed with anti-HIV immunoglobulin G (IgG) but retained Nagalase activity that is required for infectivity. Stepwise treatment of purified Gc protein with immobilized ,-galactosidase and sialidase generated the most potent macrophage activating factor (termed GcMAF), which produces no side effects in humans. Macrophages activated by administration of 100 ng GcMAF develop a large amount of Fc-receptors as well as an enormous variation of receptors that recognize IgG-bound and unbound HIV virions. Since latently HIV-infected cells are unstable and constantly release HIV virions, the activated macrophages rapidly intercept the released HIV virions to prevent reinfection resulting in exhaustion of infected cells. After less than 18 weekly administrations of 100 ng GcMAF for nonanemic patients, they exhibited low serum Nagalase activities equivalent to healthy controls, indicating eradication of HIV-infection, which was also confirmed by no infectious center formation by provirus inducing agent-treated patient PBMCs. No recurrence occurred and their healthy CD,+,cell counts were maintained for 7 years. J. Med. Virol. 81:16,26, 2009. © 2008 Wiley-Liss, Inc. [source]

    Clodronate treatment of vitamin D-induced hypercalcemia in dogs

    JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2006
    Bulent Ulutas DVM
    Abstract Objective: To determine the effects of clodronate on vitamin D3 -induced hypercalcemia in dogs. Design: Prospective experimental study. Settings: University research laboratory. Animals: Fourteen healthy intact adult male and female mixed breed dogs. Interventions: Dogs received 7.5 mg of vitamin D3/kg of body weight once orally and were randomly assigned to 2 groups of 7 dogs each. Dogs in the saline control group were given intravenous infusions of 150 mL 0.9% NaCl solution 24 hours after vitamin D3 administration. Dogs in the clodronate group were given an infusion of 4 mg/kg of clodronate in 150 mL 0.9% NaCl solution 24 hours after vitamin D3 administration. Measurements and main results: Clinical signs of vitamin D3 toxicosis were evaluated 48 hours after ingestion of vitamin D3. Dogs that were given clodronate had significantly lower serum calcium (Ca), phosphorus (P), urea, and Ca × P values than dogs in the control group on days 4, 7, and 12 after administration. Additionally, alkaline phosphatase activity was significantly lower in the clodronate group compared with dogs in the control group on days 4 and 7. Conclusions: Parenteral administration of clodronate, a biphosphonate compound and osteoclastic activity inhibitor, may be a useful therapy when administered within the first 24 hours after ingestion of toxic doses of vitamin D3. [source]

    Clinical trial: comparison of alendronate and alfacalcidol in glucocorticoid-associated osteoporosis in patients with ulcerative colitis

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009
    S. KITAZAKI
    Summary Background, Bone loss is often observed in patients with ulcerative colitis, particularly if they require glucocorticoids. Aim, To determine whether the bisphosphonate, alendronate, is safe and effective in preserving bone mass compared to the active vitamin D3, alfacalcidol, in ulcerative colitis patients receiving glucocorticoids. Methods, Thirty-nine patients with ulcerative colitis and treated with glucocorticoids were randomized to receive alendronate (5 mg/day) or alfacalcidol (1 ,g/day) daily for 12 months. Loss of bone mass was evaluated by bone mineral density, bone resorption by urinary N -telopeptide for type I collagen, and bone formation by serum bone alkaline phosphatase. Results, Alendronate, but not alfacalcidol, significantly increased bone mineral density in the lumbar spine. Alendronate decreased serum bone alkaline phosphatase levels, but alfacalcidol did not. Urinary N -telopeptide for type I collagen levels decreased in both groups, but were significantly lower in the alendronate group. There were no significant differences in the adverse events in the two groups. Conclusion, Our study indicates that alendronate is a safe, well-tolerated and more effective therapy than alfacalcidol for preventing glucocorticoid-associated bone loss in patients with ulcerative colitis. [source]

    Correcting poor vitamin D status: Do older adults need higher repletion doses of vitamin D3 than younger adults?

    MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 8 2010
    Susan J. Whiting
    Abstract We conducted an examination of recent studies to determine whether older adults (,65 years) need higher levels of supplementary vitamin D than young adults when attempting to replete vitamin D status in deficient subjects, i.e. those with levels of 25-hydroxyvitamin D less than 75,nmol/L. As data on repletion with vitamin D2 have recently been published, we restricted our discussion to the use of vitamin D3 from dietary supplements, prescriptions for large oral doses, and bolus dosing or injections. Most published dosing regimens failed to achieve 75,nmol/L in most all subjects, whether young adults (<65 years) or older adults (,65 years). Whether as daily or bolus oral supplementation, elderly subjects appeared to need more vitamin D3 compared with younger adults, however, baseline levels, endpoints, study duration, compliance, and other factors were different among studies. To ensure most subjects are replete in vitamin D, a daily dose of more than 50,,g (2000,IU) in younger and 125,,g (5000,IU) is required. Other strategies including bolus and loading doses are described. No study reported adverse effects of using oral intakes about the current upper level of 50,,g (2000,IU). [source]

    Effect of package light transmittance on the vitamin content of milk, part 3: Fortified UHT low-fat milk

    PACKAGING TECHNOLOGY AND SCIENCE, Issue 1 2009
    Alexander Saffert
    Abstract This work is the third and last part of a milk study evaluating the effect of package light transmittance on the vitamin content of milk, in this case on fortified UHT low-fat milk. The milk was stored under light with an intensity of 700,lux in polyethylene terephthalate (PET) bottles with varying light transmittance to monitor the changes in the vitamin A, B2 and D3 contents over a storage period of 12 weeks at 23°C. Milk packed in pigmented PET bottles with the lowest light transmittance, which was stored in the dark under the same experimental conditions, served as the ,control' sample. In clear PET bottles, a reduction of 93% of the initial content was observed for vitamin A and 66% for vitamin D3, while the vitamin B2 content was completely degraded. In all pigmented PET bottles, the vitamin retention was only slightly higher; the losses ranged between 70 and 90% for vitamin A, between 63 and 95% for vitamin B2, and between 35 and 65% for vitamin D3 depending on the pigmentation level. In the dark-stored ,control' sample, a 16% loss could be observed for vitamin A, while the level of vitamins B2 and D3 remained almost stable. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    PTHrP-independent hypercalcemia with increased proinflammatory cytokines and bone resorption in two children with CD19-negative precursor B acute lymphoblastic leukemia

    PEDIATRIC BLOOD & CANCER, Issue 7 2007
    Hidetaka Niizuma MD
    Abstract Hypercalcemia in childhood acute lymphoblastic leukemia (ALL) is rare and occasionally associated with parathyroid hormone-related protein (PTHrP). However, the pathogenesis of PTHrP-independent hypercalcemia remains unclear. We report two children with precursor B ALL who had marked hypercalcemia (15.8 and 16.6 mg/dl, respectively) and disseminated osteolysis. Serum tumor necrosis factor-, (TNF-,) and IL-6 were markedly elevated, whereas 1,25(OH)2 vitamin D3, intact PTH and PTHrP were decreased or undetected. Analysis of urinary deoxypyridinoline (DPY) or bone biopsy of the osteolytic lesion showed an increased bone resorption, and administration of bisphosphonate improved the hypercalcemia. Patients had ALL with immunophenotype positive for CD10, CD34, and HLA-DR but negative for CD19 and obtained remission with chemotherapy. These findings suggest that increased osteoclastic bone resorption via stimulation with TNF-, and IL-6 may be mechanism causing PTHrP-independent hypercalcemia in some patients with precursor B ALL lacking CD19 expression. Pediatr Blood Cancer 2007;49:990,993. © 2006 Wiley-Liss, Inc. [source]

    Calculated Ultraviolet Exposure Levels for a Healthy Vitamin D Status

    PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2006
    Ann R. Webb
    The dangers of overexposure to sunlight have been well publicized, but less attention has been given to an acknowledged benefit of exposure to UV radiation; that being the cutaneous synthesis of vitamin D3. Here we define a standard vitamin D dose on the basis of recently recommended requirements for vitamin D that take account of its risk reduction role in a variety of diseases, and present a web-based tool that enables the reader to calculate associated exposure times for any time and place using either default values or user-selected conditions. Either it is not possible to synthesize vitamin D3 at high latitudes in winter, or the exposure time required to reach a standard dose is sometimes impractical. Where solar UV is sufficient, a risk-benefit analysis of sunburn vs. vitamin D3 synthesis shows that the best time for brief sun exposure is in the middle of the day. For low solar elevation angles common at high latitudes, a fine line exists between adequate UV exposure for vitamin D3 synthesis and a risk of sun burn. [source]

    S179D prolactin sensitizes human prostate cancer cells such that physiological concentrations of 1, 25 dihydroxy vitamin D3 result in growth inhibition and cell death

    THE PROSTATE, Issue 14 2007
    Wei Wu
    Abstract BACKGROUND S179D Prolactin (PRL) is a molecular mimic of naturally phosphorylated human PRL which has been shown to inhibit the growth of human prostate cancer cells both in vitro and when grown as tumors in nude mice. METHODS In the current study, we have investigated the potential interplay between S179D PRL and 1,25 dihydroxy vitamin D3 (1,25D) in the inhibition of prostate cancer cell growth by incubating cells under circumstances where each hormone alone has no effect. RESULTS Incubation of DU145 or PC3 cells in 100 pM 1,25D or 10 nM S179D PRL for 3 days showed no effect of each alone on expression of the vitamin D receptor (VDR), or the cell cycle regulatory protein p21, or on cell number. Incubation in both together increased expression of the VDR and p21 two to threefold. This co-operative effect was reproduced when activation of the p21 promoter was analyzed using a p21-luciferase (p21-luc) construct. Elimination of the VDR response element from p21-luc eliminated response to the hormone combination, showing that the effect on p21 was through the VDR. Most importantly, S179D PRL sensitized the cells to 1,25D such that there was a concentration-related reduction in cell number versus controls between 40 and 160 pM. At least part of this effect was via the induction of cell death. CONCLUSIONS These results suggest that combined anti-tumor therapy may be very efficacious and that the dose of 1,25D required may be below the range that results in hypercalcemia. Prostate 67: 1498,1506, 2007. © 2007 Wiley-Liss, Inc. [source]

    1,,25-Dihydroxyvitamin D3 and its analogues, EB1089 and CB1093, profoundly inhibit the in vitro proliferation of the human hepatoblastoma cell line HepG2

    ANZ JOURNAL OF SURGERY, Issue 7 2001
    J. Akhter
    Background: 1,,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been shown to inhibit the proliferation of various cancer cells including colon, prostate, melanoma, osteosarcoma and breast cancer. Methods: The human hepatoma cell line (HepG2) was cultured with 1,25(OH)2D3 or one of two analogues EB1089 or CB1093 for various durations. Cellular proliferation was measured by uptake of [3H]thymidine, and cell numbers were determined by trypan blue exclusion counting. Results: 1,25(OH)2D3, EB1089 and CB1093 all inhibited proliferation of HepG2 by up to 90% after 5 days of treatment, compared to the untreated controls. Decreased proliferation was associated with an approximately 50% reduction in cell numbers at concentrations of up to 10,10 mol/L after 5 days of treatment with 1,25(OH)2D3. Cell proliferation rapidly recovered in cultures treated with lower concentrations of 1,25(OH)2D3 (10,10 and 10,11 mol/L) when 1,25(OH)2D3 was removed from the cultures by placing cells in serum containing medium without 1,25(OH)2D3. When HepG2 cells were treated with 10,8 mol/L 1,25(OH)2D3 for 5 weeks, there was still significant inhibition of proliferation, although at week 5 there was 66% inhibition compared to 93% at the end of week 1. Conclusions: 1,25(OH)2D3, EB1089 and CB1093 all significantly inhibit the proliferation of HepG2 hepatoblastoma cells, with EB1089 being the most potent at lower concentrations. Inhibition can be maintained for at least 4 weeks, but is reversed after removal of vitamin D3. [source]