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At least 19 recordsLinked to original sources
PubMed1981

[New findings on the metabolism and importance of the D vitamins, with special reference to the use of vitamin D].

Animal-experimental examinations show that the peroral or intramuscular application of a high dose of vitamin D2 or of D3 leads to a toxic effect of these compounds on the osteocytes and that the hypercalcaemia evoked by this is mainly to be traced back to an increased deliberation of calcium from the bones. After application of a larger dose of vitamin D the activation mechanism in the liver and in the kidneys is much inhibited for several weeks so that no formation of 1,25-hydroxy-vitamin-D takes place; consequently, no furthering effect on the mineralisation of the bones is performed. Therefore, it is recommended to use physiological doses in the prevention of rachitis (500-1,000 IU a day). During the pregnancy the activity of the enzymes which participate in the activation of the D-vitamins increases in the liver and the kidneys. The kidneys of the fetuses are able to form 1,25-hydroxy-vitamin-D. Vitamin D and 25-hydroxy-vitamin-D transgress through the placenta into the fetuses. Due to the adaptation mentioned and the increased formation of 1,25-hydroxy-vitamin-D the absorption of calcium and phosphate increases during pregnancy. Recent pathobiochemical knowledge concerning the metabolism of the D-vitamins in several diseases are described.

Bone and Bones↗
PubMed1995

Seasonal variation in vitamin D, vitamin D-binding protein, and dehydroepiandrosterone: risk of prostate cancer in black and white men.

Our previous study provided evidence that higher serum levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1, 25-D), might possibly slow the progression of subclinical to clinically significant prostate cancer in both black and white men, especially after age 57. This paper extends the prior study by contrasting seasonal variation in 1,25-D and its precursor, 25-hydroxyvitamin D (25-D), in case and control subjects. In addition, the risk of prostate cancer is related to serum levels of vitamin D-binding protein (VDBP) and total dehydroepiandrosterone and to polymorphic variation in VDBP. The expected elevated summer levels of 25-D were seen in case and control subjects and, as expected, 1,25-D did not vary throughout the year in the control subjects. Unexpectedly, lower case levels of 1,25-D were limited largely to the summer months (P = 0.01) in both black and white cases and to cases greater than or equal to the median age of 57 years. Levels of VDBP and dehydroepiandrosterone and the frequencies of VDBP polymorphisms were similar in case and control subjects, although striking differences were seen in allelic frequencies in black and white men. These observations provide additional evidence that vitamin D metabolism may impact the risk of prostate cancer.

Adult↗
PubMed1998

[D-vitamin and vitamin D deficiency among Asian immigrants].

Vitamin D deficiency, often complicated by osteomalacia, among Asian immigrants (especially females) is now also recognized in the Nordic countries. The article reviews the history of vitamin D featuring its discovery as well as a contemporary perspective, and describes the complex etiology of the disease. The symptoms, diagnostic approach and recommended treatment are also summarized.

Asia↗
PubMed1995

[The effects of long-term intake of restricted calcium, vitamin D, vitamin E and cadmium-added diets on the skeletal muscles of mice: an enzyme histochemical study].

To clarify the effect of chronic cadmium exposure on muscles, 29-day-old female ICR strain mice were separated into 7 groups and various diets were given to each group. Group I a commercial diet (Intact), Group II a diet low in calcium and low in vitamin D, Group III a diet low in Ca, low in D and low in vitamin E, Group IV a low in Ca, low in D and 20ppm cadmium-added diet, Group V a low in Ca, low in D and 40ppm Cd diet, Group VI a low in Ca, low in D, low in E and 20ppm Cd diet and Group VII a low in Ca, low in D, low in E and 40ppm Cd diet. The levels of vitamin D and vitamin E were designed to be low in each diet but their amounts fulfilled the minimum nutritional requirements. The experimental period was long, ranging from 29 days to 24 months. Using a microscope, two skeletal muscles, the soleus (red muscle) and the gastrocnemius (white muscle) of mice with chronic Cd effects were observed after staining with H. E. and analyzed after enzyme histochemical reaction to ATPase. Using ATPase stain, type I muscle fibers were distinguished from type II muscle fibers. The long-term effects of cadmium. 1) Comparisons among groups II, IV and V. After 18 months it was found in group IV that myopathic muscle damage (increased random variation of fiber size [Size] and widening of interstitial tissue [Widening]) were more prominent that in group II. In group V myopathic muscle damage (Size and Widening) and type II atrophy were more prominent that in group IV. At 24 months it was found in group IV that myopathic muscle damage (Size, internal nuclei [IN] and Widening) and type I and type II atrophy were more prominent than in group II. In group V myopathic muscle damage (Size, IN and Widening) and type I and type II atrophy were more prominent than in group IV. 2) Comparisons among group III, VI and VII.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1982

Inhibition of the in vitro growth of Plasmodium falciparum by D vitamins and vitamin D-3 derivatives.

D vitamins are effective inhibitors of the in vitro intraerythrocytic growth of Plasmodium falciparum. Disappearance of the parasitemia was observed after 48 h contact between infected cells and 5 x 10(-6) M 1 alpha-hydroxycholecalciferol, 5 x 10(-5) M 25-hydroxycholecalciferol (25-OH-D-3), 1 alpha, 25-dihydroxycholecalciferol or 2.5 x 10(-4) vitamin D-2 and D-3. A 48 h pretreatment of healthy erythrocytes with 5 x 10(-5) M 25-OH-D-3 did not change their susceptibility to invasion by the parasite and their ability to support the growth of P. falciparum. Ionomycin, a calcium ionophore, and EGTA prevented parasite development at concentrations greater than 2 x 10(-7) M and 4 x 10(-4) M, respectively, but did not antagonize the inhibitory activity of 25-OH-D-3. Addition of 25-OH-D-3 for 12 or 24 h duration to synchronized cultures, showed that the drug had a schizonticidal action, but was without effect when parasites were in the ring form.

Animals↗
PubMed1995

[New fluorogenic dienophile: synthesis, reaction with vitamin D, vitamin A and microcystins, and application to fluorometric assays].

We designed and synthesized a new sensitive and highly reactive fluorogenic reagent (1a, DMEQ-TAD) targeting a conjugated diene. DMEQ-TAD reacted quantitatively with major vitamin D metabolites and synthetic analogs under a variety of conditions to yield the corresponding 6,19-cycloadducts as a mixture of the C(6) epimers. The stereochemistry of the adducts was determined by their CD spectra on the basis of the exciton chirality method. The fluorescent products can be quantified linearly down to 10 fmol by HPLC. The new fluorometric method was successfully used in the assays of 25-OHD3, 24,25-(OH)2D3 and 25,26-(OH)2D3 in the human plasma. The method was proved to be reliable and precise compared with the HPLC-UV assay method. Reactions of DMEQ-TAD with retinoic acid (21a) and its geometrical isomers (21b-d) having a conjugated pentaene system afforded 7,10-adducts (24a-d) as major products together with 5,8-adducts (26a-d) in about 9:1 ratio (70-95% yield) except for the 9Z-isomer (21e) which gave only a 5,8,11,14-bis-adduct (27). DMEQ-TAD reacted with microcystins LR, YR and RR, at the conjugated diene part to yield 4,7-cycloadducts as a pair of epimers in good yield.

Fluorescent Dyes↗
PubMed2000

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Due to their known effects on bone metabolism, Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures. OBJECTIVES: To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, BIOSIS, CINAHL, HealthPLAN, Dissertation Abstracts, Index to UK Theses, Current Contents, and bibliographies of identified trials and reviews. Trials were also obtained from the Cochrane Musculoskeletal Injuries Group trials register. Date of the most recent search: December 1995. SELECTION CRITERIA: Any randomised or quasi-randomised trial which compared Vitamin D or a Vitamin D analogue, either alone or in combination with calcium supplementation, with a placebo, no intervention, or the administration of calcium supplements, with fracture as an outcome, in elderly men or women with involutional or post-menopausal osteoporosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of a seven item scale, and extracted data. Additional information was sought from trialists. Where possible the data were pooled. MAIN RESULTS: Fourteen trials recording 13 different comparisons were included. In the only trial of Vitamin D alone, protection against hip fracture was not confirmed. Two regimens, each represented by one large trial, which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were: 1) Oral Vitamin D when accompanied by calcium supplementation. 2) 1,25 dihydroxy Vitamin D (calcitriol). This appeared more effective than calcium in a direct comparison. Regimens showing limited evidence of efficacy in reducing the incidence of vertebral deformity were: 1) 1,25 dihydroxy Vitamin D (calcitriol), which appeared more effective than calcium in one large trial, and more effective than placebo from pooled results of two small trials. 2) Oral 1-alpha hydroxy Vitamin D (alfacalcidol), when administered with calcium supplements (two small trials, which lacked power to confirm a possible effect). Hypercalcaemia and gastro-intestinal symptoms, reported in less than 5% of participants, were slightly more common when Vitamin D analogues were taken. However, the risk of death was marginally less. REVIEWER'S CONCLUSIONS: Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention. Particularly if co-supplementation of calcium is required, significant cost differences are likely to exist between regimens. Further randomised trials with economic evaluation are desirable before community fracture prevention programmes employing Vitamin D supplementation can be confidently introduced.

Aged↗
PubMedDate not supplied

Three-dimensional structure-function relationship of vitamin D and vitamin D receptor model.

On the basis of conformational analysis of the vitamin D side chain and studies using conformationally restricted synthetic vitamin D analogs, we have suggested the active space region concept of vitamin D: The vitamin D side-chain region was grouped into four regions (A, G, EA and EG) and the A and EA regions were suggested to be important for vitamin D actions. We extended our theory to known highly potent vitamin D analogs and found a new region F. The analogs which occupy the F region have such modifications as 22-oxa, 22-ene, 16-ene and 18-nor. Altogether, the following relationship between the space region and activity was found: Affinity for vitamin D receptor (VDR), EA > A> F > G > EG; Affinity for vitamin D binding protein (DBP), A >> G,EA,EG; Target gene transactivation, EA > F > A > EG > or = G; Cell differentiation, EA > F > A > EG > or = G; Bone calcium mobilization, EA > GA > F > or = EG; Intestinal calcium absorption, EA = A > or = G >> EG. We modeled the 3D structure of VDR-LBD (ligand binding domain) using hRARgamma as a template, to develop our structure-function theory into a theory involving VDR. 1alpha,25(OH)(2)D(3) was docked into the ligand binding pocket of the VDR with the side chain heading the wide cavity at the H-11 site, the A-ring toward the narrow beta-turn site, and the beta-face of the CD ring facing H3. Amino acid residues forming hydrogen bonds with the 1alpha- and 25-OH groups were specified: S237 and R274 forming a pincer type hydrogen-bond for the 1alpha-OH and H397 for the 25-OH. Mutants of several amino acid residues that are hydrogen-bond candidates were prepared and their biologic properties were evaluated. All of our mutation results together with known mutation data support our VDR model docked with the natural ligand.

Animals↗
PubMed1993

Exogenous calciferol (vitamin D) and vitamin D endocrine status among elderly nursing home residents in the New York City area.

OBJECTIVE: To determine the role and relative importance of sources of exogenous calciferol (vitamin D) in maintaining vitamin D endocrine status in the mid-winter and early spring in a representative sample of institutionalized elderly persons in the New York City area. DESIGN: Cross-sectional survey. SETTING: A privately-run urban nursing home and the long-term care unit of a suburban public hospital. PARTICIPANTS: Residents aged 60 years and older scheduled for a routine annual physical examination and an additional group of individuals ascertained by random sampling. Those with a history of anti-convulsant or glucocorticoid use, liver disease, chronic renal disease (or serum creatinine > 1.5 mg/dL), parathyroid disease, Paget's disease, gastric surgery, or pharmacological vitamin D use were excluded. Of 301 sampled individuals, 221 were found eligible to participate, and 109 were successfully enrolled. RESULTS: The average vitamin D intake was 379 IU/day (range 55-1006 IU/day) and total vitamin D intake was below the Recommended Dietary Allowance in 16% of subjects. Fifty percent of total vitamin D intake came from fortified milk, and 26% came from vitamin supplements. Vitamin supplement use was not associated with low dietary intake. Among subjects taking a supplement containing 400 IU/day, none had serum calcidiol levels below 15 ng/mL, while among subjects with vitamin D intake between 200 and 400 IU/day, 46% had serum calcidiol levels below 15 ng/mL and 14% had calcidiol levels below 10 ng/mL. Vitamin D intake from non-supplement sources (but not from supplements) appeared to have a negative association with serum calcitriol levels. CONCLUSIONS: Many nursing home residents may require vitamin supplements in order to achieve optimal levels of calciferol replacement. The choice of a vehicle for calciferol replacement may affect calcitriol levels.

Aged↗
PubMed2003

Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants.

OBJECTIVE: To determine the prevalence of hypovitaminosis D in exclusively breast-feeding infants and their mothers in a community where maternal sunshine exposure is low. STUDY DESIGN: Serum levels of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D (25-OHD), and intact parathyroid hormone were measured in 90 unsupplemented healthy term breast-feeding Arab/South Asian infants and their mothers in summer. Maternal dietary vitamin D intake was also estimated. RESULTS: The median age of infants was 6 weeks. The median serum 25-OHD concentrations in mothers (8.6 ng/mL) and infants (4.6 ng/mL) were low, and 61% of the mothers and 82% of the 78 infants tested had hypovitaminosis D (serum 25-OHD <10 ng/mL). The infants with hypovitaminosis D had elevated serum alkaline phosphatase and a tendency to higher serum intact parathyroid hormone levels. The average daily maternal vitamin D intake from commercial milk was 88 IU. CONCLUSIONS: Hypovitaminosis D is common in summer in exclusively breast-feeding infants and their mothers. The results provide justification for vitamin D supplementation of breast-feeding infants and mothers in the United Arab Emirates. Low vitamin D intake probably contributed to low maternal vitamin D status.

25-Hydroxyvitamin D 2↗
PubMed2002

Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease.

Vitamin D plays a pivotal role in the pathogenesis and treatment of renal bone disease. Vitamin D levels decline in the early phase of renal failure, however, through a compensatory mechanism parathyroid hormone (PTH) stimulates the production of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) to return it to normal circulating concentrations. Nevertheless, resistance to calcitriol is observed and may be related to the decreased presence of the heterodimeric, DNA-binding partner for the vitamin D receptor protein. In end-stage kidney disease (ESKD) the circulating levels of calcitriol are invariably low. The indications of vitamin D therapy are the replacement of the missing hormone vs suppression of hyperparathyroidism (HPT) requiring daily low-dose oral vs intermittent 'pulse' or oral administration. However, this therapy must be accompanied by careful patient monitoring to avoid hypercalcaemia and low bone turnover. Low bone turnover is not merely a histologic entity, but a clinical condition associated with a high risk of extraosseous calcifications, in particular in the cardiovascular system, leading to increased morbidity. Thus, determination of bone turnover in patients with ESKD is essential. Bone biopsy is the gold standard to assess bone turnover, however, it is not always available and nephrologists rely on PTH levels. The intact PTH assay measures PTH(1-84) and large C-PTH fragments, which may antagonize the PTH(1-84) effects on bone. An assay that measures exclusively PTH(1-84) has recently become available and a calculated PTH(1-84)/C-PTH fragment ratio has been shown to be the best predictor of bone turnover in patients with ESKD not treated with vitamin D or with other medications known to affect bone metabolism. 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is a vitamin D analogue that could control serum PTH concentrations without deleterious effects on bone.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed2003

Vitamin D and vitamin D analogs as cancer chemopreventive agents.

Epidemiologic studies have associated vitamin D, attained through nutrition and sun exposure, with reduced cancer risk. Although dose-limiting hypercalcemia has limited the use of natural vitamin D in cancer prevention, several promising new synthetic vitamin D analogs (deltanoids) are under development. Examples are KH-1060, EB-1089, 1alpha-hydroxyvitamin D5, vitamin D2, and QW-1624F2-2. Clinical targets for deltanoids include colon, prostate, and breast. Studies to elucidate the molecular mechanisms underlying the observed efficacy of deltanoids are ongoing. The vitamin D receptor, a steroid/thyroid receptor superfamily member, appears to control most deltanoid effects on proliferation, apoptosis, differentiation, and angiogenesis.

Animals↗
PubMed1979

Analysis of fat-soluble vitamins. XXI. High pressure liquid chromatographic assay methods for vitamin D in vitamin D concentrates.

Two high pressure liquid chromatographic methods, a straight and a reverse phase system, were developed and compared with the official (chemical) AOAC method for vitamin D concentrates. The effects of the systematic error and the reproducibility of using an internal or external standard were studied, as well as the effect of using peak height or peak height X retention time for calculating the potential vitamin D content. A method is given for determining the conversion factor to calculate previtamin D as vitamin D. Based on the results of the comparison, the following conditions were selected for collaborative study: straight phase, amyl alcohol-hexane mobile phase, external standard, and calculation of potency by peak height.

Cholecalciferol↗
PubMed1990

Bone disease in chronic childhood cholestasis. II. Better absorption of 25-OH vitamin D than vitamin D in extrahepatic biliary atresia.

Infants with extrahepatic biliary atresia (EHBA) commonly develop rickets in infancy, whereas long-term survivors with EHBA commonly develop osteopenia with increasing age. We evaluated baseline vitamin D (D2 and D3), 25-OH vitamin D2 and D3, 1,25(OH)2 vitamin D, bone mineral content, and vitamin D2 and 25-OH vitamin D3 absorption in six infants and children (age 4-22 mo) with EHBA whose portoenterostomy failed to produce bile flow (group 1) and five infants and children (age 10/12 to 8-4/12 y) with EHBA whose portoenterostomy repair led to good postoperative bile flow (group 2). Baseline serum vitamin D2 and D3 were undetectable in all subjects in group 1 despite supplements of 2500-5000 IU/day, whereas all group 2 subjects given supplements (doses 400-5000 IU/d) had measurable levels. Baseline serum 25-OH vitamin D was less than 15 ng/mL in five of six (three with rickets) in group 1, whereas only one in group 2 had concentrations less than 15 ng/mL. A significantly blunted rise of vitamin D2 above baseline and reduced area under the absorption curve after 1000 IU/kg vitamin D2 were found in group 1 patients compared to group 2 (both p less than 0.01), and five pediatric controls (both p less than 0.01). The peak change and area under the absorption curve for serum 25-OH vitamin D3 from baseline after 10 micrograms/kg 25-OH vitamin D3 were significantly reduced for group 1 (both at least p less than 0.05) and group 2 compared to controls (both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary Atresia↗
PubMed1980

Vitamin D and vitamin D dependency.

Administration of large doses of vitamin D2 brought about a marked increase of 25-hydroxyvitamin D in both the patients with vitamin D dependency and hypophosphatemic vitamin D-resistant rickets. During the administration of vitamin D2, increment of 1,25-dihydroxyvitamin D was marked in hypophosphatemic vitamin D-resistant rickets, but far smaller in vitamin D dependency. In the latter, however, the 1,25-dihydroxyvitamin D reached the level close to the normal adult values. 1 alpha-hydroxyvitamin D3 was found 50 approximately 100 times as effective as vitamin D2 in 2 patients with vitamin D dependency (optimum maintenance dose: 0.05 micrograms/kg/day). It was concluded that 1 alpha-hydroxylation in the renal tubules is markedly defective in the patients with vitamin D dependency, but that a large dose of vitamin D2 is able to cause a definite increase in serum concentration of 1,25-dihydroxyvitamin D resulting in improvement of the rickets.

Alkaline Phosphatase↗