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PubMedDate not supplied

Lipopolysaccharide negatively modulates vitamin D action by down-regulating expression of vitamin D-induced VDR in human monocytic THP-1 cells.

Vitamin D3, an important seco-steroid hormone for the regulation of body calcium homeostasis, promotes immature myeloid precursor cells to differentiate into monocytes/macrophages. Vitamin D receptor (VDR) belongs to a nuclear receptor super-family that mediates the genomic actions of vitamin D3 and regulates gene expression by binding with vitamin D response elements in the promoter region of the cognate gene. Thus by regulating gene expression, VDR plays an important role in modulating cellular events such as differentiation, apoptosis, and growth. Here we report lipopolysaccharide (LPS), a bacterial toxin; decreases VDR protein levels and thus inhibits VDR functions in the human blood monocytic cell line, THP-1. The biologically active form of vitamin D3, 1alpha,25-dihydroxy vitamin D3 [1,25(OH)2D3], induced VDR in THP-1 cells after 24 h treatment, and LPS inhibited 1,25(OH)2D3-mediated VDR induction. However, LPS and 1,25(OH)2D3 both increased VDR mRNA levels in THP-1 cells 20 h after treatment, as observed by real time RT-PCR. Moreover, LPS plus 1,25(OH)2D3 action on VDR mRNA level was additive and synergistic. A time course experiment up to 60 h showed an increase in VDR mRNA that was not preceded with an increase in VDR protein levels. Although the proteasome pathway plays an important role in VDR degradation, the proteasome inhibitor lactacystin had no effect on the LPS-mediated down-regulation of 1,25(OH)2D3 induced VDR levels. Reduced VDR levels by LPS were accompanied by decreased 1,25(OH)2D3/VDR function determined by VDR responsive 24-hydroxylase (CYP24) gene expression. The above results suggest that LPS impairs 1,25(OH)2D3/VDR functions, which may negatively affect the ability of 1,25(OH)2D3 to induce myeloid differentiation into monocytes/macrophages.

Cell Line↗
PubMed2000

Effect of vitamin A palmitate on vitamin A-deficient rabbits

Purpose: We examined the effects of vitamin A palmitate (VA pal) eyedrops on the symptoms caused by vitamin A-deficiency in rabbits. Methods: Three-week-old rabbits were raised on a vitamin A-deficient diet, and were examined for the quantity of retinol in the serum and the condition of the anterior segment of the eye. The vitamin A-deficient animals were treated with VA pal eyedrops.Results: The retinol in the serum began to decrease 7 months after the animals were placed on the vitamin A-deficient diet. After 10 months, superficial punctate keratitis and the loss of conjunctival goblet cells were observed. Treatment of the disease in the anterior segment of the eyes with VA pal eyedrops resulted in restoration of normal condition within 3 weeks. The treatment increased the goblet cells in the ocular conjunctiva and the retinol in the serum. Conclusions: These results show the efficacy of topical VA pal treatment for vitamin A-deficient rabbits.

Journal Article↗
PubMed1978

High-performance liquid chromatography determination of potential content of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in resins, oils, dry concentrates and multivitamin formulations.

The determination of potential vitamin D concentrations in raw materials and in multivitamin formulations by high-performance liquid chromatography is reported. Simple experimental conditions allow the rapid separation of the vitamins from their respective pro- and pre-vitamins, from their irradiation side-products and from some of their overirradiation products. Vitamin extraction is performed directly from dry concentrates, tablets and capsules, without saponification; all procedures are carried out at room temperature so as to preserve the ratio of vitamin D and pre-vitamin D present in the prepatation. The relative standard deviation is less than 1.5%.

Cholecalciferol↗
PubMed2000

Synthesis and biological activities of the two C(23) epimers of 1alpha,23,25-trihydroxy-24-oxo-19-nor-vitamin D(3): novel analogs of 1alpha,23(S),25-trihydroxy-24-oxo-vitamin D(3), a natural metabolite of 1alpha,25-dihydroxyvitamin D(3).

In a previous report, we indicated that 1alpha,23(S), 25-trihydroxy-24-oxovitamin D(3) [1alpha,23(S), 25(OH)(3)-24-oxo-D(3)], a natural metabolite of 1alpha, 25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] is almost equipotent to 1alpha,25(OH)(2)D(3) in suppressing parathyroid hormone (PTH) secretion (Lee et al., 1997. Biochemistry 36, 9429-9437). Also, 1alpha,23(S),25(OH)(3)-24-oxo-D(3) has been shown to possess only weak in vivo calcemic actions. Thus, vitamin D(3) analogs structurally related to 1alpha,23(S),25(OH)(3)-24-oxo-D(3) may have therapeutic value. Furthermore, biologic activity studies of various synthetic analogs of 1alpha,25(OH)(2)D(3) showed that the removal of carbon-19 (C-19) reduces the calcemic activity of 1alpha, 25(OH)(2)D(3.) Therefore, in an attempt to produce vitamin D(3) analogs with a better therapeutic index, we synthesized C(23) epimers of 1alpha,23,25(OH)(3)-24-oxo-19-nor-vitamin D(3) [1alpha,23, 25(OH)(3)-24-oxo-19-nor-D(3)]. The two epimers were compared to 1alpha,25(OH)(2)-19-nor-D(3) and 1alpha,25(OH)(2)D(3) in their ability to generate biologic activities in several in vitro assay systems. In the assay measuring the suppression of parathyroid hormone (PTH) secretion in bovine parathyroid cells, 1alpha,23(S), 25(OH)(3)-24-oxo-19-nor-D(3) was as potent as 1alpha, 25(OH)(2)-19-nor-D(3) but was less potent than 1alpha,25(OH)(2)D(3). In the same assay 1alpha,23(R),25(OH)(3)-24-oxo-19-nor-D(3) exhibited greater potency than 1alpha,23(S), 25(OH)(3)-24-oxo-19-nor-D(3). In the assays measuring the ability of vitamin D compounds to inhibit clonal growth and to induce differentiation of human promyelocytic leukemia (HL-60) cells, 1alpha,23(S),25(OH)(3)-24-oxo-19-nor-D(3) was less potent than 1alpha,25(OH)(2)-19-nor-D(3) but was equipotent to 1alpha, 25(OH)(2)D(3). More importantly, in the same assays, 1alpha,23(R), 25(OH)(3)-24-oxo-19-nor-D(3) was more potent than 1alpha,23(S), 25(OH)(3)-24-oxo-19-nor-D(3) and was equipotent to 1alpha, 25(OH)(2)-19-nor-D(3). Also, the vitamin D receptor-mediated transcriptional activity of 1alpha,23(R), 25(OH)(3)-24-oxo-19-nor-D(3) was almost equal to that of 1alpha, 25(OH)(2)-19-nor-D(3), but higher than that of 1alpha,23(S), 25(OH)(3)-24-oxo-19-nor-D(3). This finding explains in part the greater in vitro biologic activities of 1alpha,23(R), 25(OH)(3)-24-oxo-19-nor-D(3). In summary, our results indicate that 1alpha,23(R),25(OH)(3)-24-oxo-19-nor-D(3) and to a lesser extent 1alpha,23(S),25(OH)(3)-24-oxo-19-nor-D(3) are potent 19-nor vitamin D(3) analogs, which suppress PTH secretion in bovine parathyroid cells and strongly inhibit clonal growth and induce differentiation of HL-60 cells in vitro.

Animals↗
PubMedDate not supplied

Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial.

BACKGROUND: Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures. METHODS: In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures. FINDINGS: 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups. INTERPRETATION: The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.

Accidental Falls↗
PubMed1997

Helix-loop-helix-type transcription factor (HES-1) is expressed in osteoblastic cells, suppressed by 1,25(OH)2 vitamin D3, and modulates 1,25(OH)2 vitamin D3 enhancement of osteopontin gene expression.

The active form of vitamin D, 1,25(OH)2 vitamin D3 (D3), is a potent modulator of osteoblastic function. In this study, we examined, the expression of a negative-type basic helix-loop-helix transcription factor, HES-1, in osteoblastic cells and the regulation of its expression by D3. We found that HES-1 is expressed as a 1.7 kb mRNA in rat osteoblastic osteosarcoma ROS17/2.8 cells. Treatment with D3 suppressed HES-1 mRNA levels by about 50%. This suppression was observed within 24 h and lasted for at least 48 h. The suppressive effect was dose-dependent starting at 10(-9) mol/L and saturated at 10(-8) mol/L. The vitamin D3 suppression of HES-1 mRNA level was blocked by actinomycin D as well as cycloheximide, suggesting the involvement of transcriptional control, which requires new protein synthesis. Proteins in the crude nuclear extracts prepared from ROS17/2.8 cells bound to the N-box sequence (CACNAG). To examine the function of HES-1 in osteoblasts, HES-1 was overexpressed in ROS17/2.8 cells. Overexpression of HES-1 suppressed the vitamin D-dependent upregulation of osteopontin gene expression in these cells. Vitamin D suppression of HES-1 gene expression was also observed in normal rat calvaria-derived osteoblast-enriched cells. These results indicate that HES-1 is expressed in osteoblastic cells and is involved in vitamin D3 regulation of osteoblastic gene expression.

Animals↗
PubMed1996

Estimation of vitamin needs--riboflavin, vitamin B6 and ascorbic acid-according to blood parameters and functional-cognitive and emotional indices in a selected well-established group of elderly in a home for the aged in Israel.

OBJECTIVE: To evaluate the vitamin status and the effects of micronutrient supplementation as determined by biochemical assays and functional, cognitive and emotional tests in a selected well-established group of elderly people, average age above 80 years. METHODS: Dietary consumption was evaluated by in-person interview using a food frequency questionnaire. Medical, biochemical, nutritional, functional, cognitive and behavioral parameters were assessed in elderly subjects (n = 12) living in a home for the aged, at baseline and after 42 days of micronutrient supplementation. The same parameters were assessed in additional subjects (n = 9), at baseline only. RESULTS: In all subjects, most of the micronutrients were not supplied at an adequate level. Supplementation of micronutrients at a level of 100% RDA improved parameters related to vitamin status, the activation coefficients (AC) of GR (glutathione reductase) and AST, blood ascorbic acid concentrations, functional-cognitive evaluation values, blood pressure, pulse rate, and serum cholesterol and triglycerides levels. At baseline, the following parameters significantly correlated with vitamin intake and were used for the estimation of vitamin needs: AC of GR, Tinetti Balance Evaluation, FIM and recorded morbidity. CONCLUSIONS: On the basis of limited available data, calculation of vitamin needs based on regression lines resulted in estimates (mg/day) of: > 150 for ascorbic acid, > 3 for riboflavin, > 3 for vitamin B6. Expanding the current practice of supplementing micronutrients at a level of 100% RDA (in tablet form) that already exists in some elderly societies should be considered after a comprehensive study in a large group of elderly people.

Aged↗
PubMed1999

The influence of dietary restriction on vitamin B-6 vitamer distribution and on vitamin B-6 metabolizing enzymes in rats.

OBJECTIVE: The purpose of this study was to assess the effect of dietary restriction on tissue distribution of vitamin B-6 vitamers and activities of vitamin B-6 metabolizing enzymes in rats. METHODS: Male rats were subjected to a 40% dietary restriction for 10, 20 or 40 weeks. The tissue vitamin B-6 vitamer concentrations and activities of the vitamin B-6 metabolizing enzymes of the animals were determined. RESULTS: The plasma pyridoxal 5'-phosphate (PLP) concentrations of the diet-restricted (DR) rats were comparable to those of the control group at week ten but were significantly lower at weeks 20 and 40. These significantly lower levels of plasma PLP in DR rats might in part be related to lower hepatic pyridoxal kinase and pyridoxamine (pyridoxine) 5'-phosphate oxidase activities. The urinary 4-pyridoxic acid excretion of the DR groups responded to the reduced food intake and were lower at weeks 10 and 20. Tissue levels of PLP were not affected by dietary restriction. In contrast, greater levels of pyridoxamine 5'-phosphate were found in liver, kidney and heart of the DR animals. CONCLUSION: The duration of dietary restriction influenced the distribution of vitamin B-6 vitamers. When plasma PLP is used to evaluate vitamin B-6 status, the length of dietary restriction should be considered.

Animals↗
PubMed1983

Vitamin D nutritional status of premature infants supplemented with 500 IU vitamin D2 per day.

The vitamin D nutritional status of premature infants was assessed by determining plasma 25-hydroxyvitamin D concentrations before and during supplementation with 500 IU vitamin D2 per day. Fifty-one samples were collected from 25 healthy infants fed breast milk and a vitamin D3 fortified formula. Gestational age was 32.2 +/- 2.4 weeks (mean +/- 1 SD). 25-hydroxyvitamin D levels before supplementation correlated well with maternal values (r = 0.81). The infants' mean plasma concentration increased from 30.6 +/- 13.7 nmol/l (mean +/- 1 SD) after birth to 46.3 +/- 10.5 nmol/l after 9 +/- 1 days (p less than 0.0025), and to 65.3 +/- 16.6 nmol/l after 37 +/- 10 days of vitamin D2 treatment (p less than 0.0005). 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 were determined separately, and it appeared that the rise was accounted for by the D2 fraction while 25-hydroxyvitamin D3 concentrations were unchanged. The results demonstrate that vitamin D2 is well absorbed and hydroxylated in the 25 position by premature infants free of associated disease, and that a supplementation of 500 IU per day in addition to breast milk and a regular vitamin D fortified formula is adequate to rapidly establish 25-hydroxyvitamin D levels within the normal adult range.

25-Hydroxyvitamin D 2↗
PubMed1987

Serum levels of vitamin C in relation to dietary and supplemental intake of vitamin C in smokers and nonsmokers.

Serum vitamin C levels were compared in smokers and nonsmokers in relation to dietary and supplemental intake of vitamin C, using data from the Second National Health and Nutrition Examination Survey. Smokers reported a lower mean daily intake (53 mg) of vitamin C than nonsmokers (65 mg) and a higher percentage (41% compared to 31%) consuming less than 70% RDA. Smoking status of respondents was judged by carboxyhemoglobin levels or by questionnaire. With both methods, percent of nonsupplemented smokers with serum vitamin C 0.3 mg/dl or less was two or more times as high as nonsupplemented nonsmokers at similar dietary intake levels. When smokers and nonsmokers with similar dietary vitamin C intake were ranked by serum C level, median and mean serum C for smokers was consistently lower than nonsmokers by approximately 0.2 mg/dl. By using the parallel bioassay methods, it was estimated that smokers would need an additional 59 mg/day dietary vitamin C (95% confidence interval of 52-68 mg/day) based on median values or 65 mg/day (53-79 mg/day) based on mean values to attain serum C levels comparable to nonsmokers.

Adolescent↗
PubMed2006

Inhibition of p38 by vitamin D reduces interleukin-6 production in normal prostate cells via mitogen-activated protein kinase phosphatase 5: implications for prostate cancer prevention by vitamin D.

Although numerous studies have implicated vitamin D in preventing prostate cancer, the underlying mechanism(s) remains unclear. Using normal human prostatic epithelial cells, we examined the role of mitogen-activated protein kinase phosphatase 5 (MKP5) in mediating cancer preventive activities of vitamin D. Up-regulation of MKP5 mRNA by 1,25-dihydroxyvitamin-D3 (1,25D) was dependent on the vitamin D receptor. We also identified a putative positive vitamin D response element within the MKP5 promoter that associated with the vitamin D receptor following 1,25D treatment. MKP5 dephosphorylates/inactivates the stress-activated protein kinase p38. Treatment of prostate cells with 1,25D inhibited p38 phosphorylation, and MKP5 small interfering RNA blocked this effect. Activation of p38 and downstream production of interleukin 6 (IL-6) are proinflammatory. Inflammation and IL-6 overexpression have been implicated in the initiation and progression of prostate cancer. 1,25D pretreatment inhibited both UV- and tumor necrosis factor alpha-stimulated IL-6 production in normal cells via p38 inhibition. Consistent with inhibition of p38, 1,25D decreased UV-stimulated IL-6 mRNA stabilization. The ability of 1,25D to up-regulate MKP5 was maintained in primary prostatic adenocarcinoma cells but was absent in metastases-derived prostate cancer cell lines. The inability of 1,25D to regulate MKP5 in the metastasis-derived cancer cells suggests there may be selective pressure to eliminate key tumor suppressor functions of vitamin D during cancer progression. These studies reveal MKP5 as a mediator of p38 inactivation and decreased IL-6 expression by 1,25D in primary prostatic cultures of normal and adenocarcinoma cells, implicating decreased prostatic inflammation as a potential mechanism for prostate cancer prevention by 1,25D.

Calcitriol↗