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At least 685 records · Page 38Linked to original sources
PubMed1982

The effect of toxic doses of 1,25-dihydroxycholecalciferol on dental tissues in the rat.

Vitamin D-depleted rats 4-weeks old were divided into three groups and given daily for 5 weeks cholecalciferol (0.25 microgram) or 1,25(OH)2D3 (0.075 microgram). The third group received no treatment with vitamin D sterols. A fourth control group was fed a diet containing vitamin D. The animals were killed after 5 weeks, plasma was prepared for calcium analysis, and incisors and molars were taken for histology. Growth was monitored throughout. Plasma calcium, body weight and the physical condition of the 1,25(OH)2D3-treated animals indicated that they were toxemic. The pulp-dentine complex of their incisors showed premature aging of fibroblasts and odontoblasts, disturbances in the dentinal matrix and osteodentine formation. That of molars was not affected. There was hypercementosis and bone-like tissue formation in the periodontal-ligament which in the incisors was considerably enlarged; some molars were ankylosed. The pulp-dentine complex of the incisors and molars of the rats in the remaining three groups appeared normal except for zones of hypomineralization in incisors of the third group. The supporting tissues of the teeth of the rats in the other three groups were within normal limits. Thus toxic doses of 1,25(OH)2D3 affected the dental tissues of both developing and mature teeth.

Animals↗
PubMed1981

Structural requirements of sterols for myelin tube formation with sodium oleate.

Cholesterol crystals treated with an aqueous solution of sodium oleate give rise to cylindrical lamellar associations which appear under the microscope as rapidly growing tubes. Myelin forms are also obtained with other membrane sterols (desmosterol, cholestanol, 7-dehydrocholesterol) but not with lanosterol, a metabolic precursor of cholesterol, nor with the catabolic products of cholesterol (coprosterol, cholecalciferol, pregnenolone). The structural requirements for obtaining myelin tubes from sterols and sodium oleate closely agree with the results obtained by studying sterol-lecithin associations using other experimental techniques (unimolecular films at the air/water interface and permeability of liposomes), association of sterols with an erythrocyte protein and cholesterol liquid crystals.

Chemical Phenomena↗
PubMed1983

Vitamin D3 metabolites in rat epididymis: high 24,25-dihydroxy vitamin D3 levels in the cauda region.

Normal male rats received six subcutaneous injections of 8.0 pmoles of tritiated 25-hydroxy vitamin D3 ([3H]25(OH)D3) or one intrajugular injection of 8.0 pmoles of high specific radioactivity [3H]-25(OH)D3. Lipid extracts of several tissues including the reproductive organs were subjected to sephadex LH-20 chromatography to determine the tissue distribution of the injected material and of the in vivo produced dihydroxylated cholecalciferol metabolites. The nature of the putative 25(OH)D3 and the 24,25-dihydroxy vitamin D3 (24,25(OH)2D3) from epididymis tissue was confirmed by high performance liquid chromatography (HPLC). The epididymis levels of 24,25(OH)2D3 were considerably higher in the cauda epididymis compared to kidney and caput epididymis levels. The other metabolites levels in this tissue were similar to those determined in the kidneys. The amounts of the three metabolites found in all other tissues were well below the cauda epididymis or kidney levels. The findings suggest a possible physiological role for 24,25(OH)2D3 in the epididymis, and are also consistent with data of others which indicated a possible action of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in rat reproductive tissues.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Inhibition of insulin receptor binding by A23187: synergy with phorbol esters.

The ionophore A23187 inhibits the binding of insulin on U-937 monocyte-like cells which had been induced to differentiate by 1 alpha, 25-(OH)2 cholecalciferol, while it remains inactive on the undifferentiated cells. A 50% reduction of the specific binding of 125I-insulin is observed within 20 to 30 min at 37 degrees C. The effect is obtained at 10(-7)M to 10(-6)M A23187. It is reversible in 60 min at 37 degrees C. A suboptimal concentration of the ionophore potentiates the inhibitory action of phorbol esters on insulin binding.

Calcimycin↗
PubMed1985

Pituitary 1,25-dihydroxyvitamin D3 receptors in hyperthyroid- and hypothyroid-rats.

The binding of 1 alpha,25-dihydroxy (26,27-methyl-[3H]) cholecalciferol ([3H]1,25-(OH)2D3) to its receptor in cytosol of the anterior pituitary cells was examined in hyperthyroid- and hypothyroid rats, as well as in normal rats. The binding capacity increased by 41% in L-Thyroxine-treated hyperthyroid rats and decreased by 49% in propylthiouracil-ingested hypothyroid rats as compared with normal control rats, whereas the affinity of the receptor for [3H]-1,25(OH)2D3 showed no difference among these 3 animal groups. These findings indicate that the number of 1,25(OH)2D3 receptors in the pituitary may be regulated by thyroid hormone, and further suggest that 1,25-(OH)2D3 may play some role in regulating functions of the anterior pituitary.

Animals↗
PubMed1991

1,25(OH)2-D3 is a potent regulator of interleukin-1 induced interleukin-8 expression and production.

Interleukin 8 (IL-8) is a potent leukocyte chemotactic and activating cytokine produced by keratinocytes, fibroblasts, peripheral blood monocytes (PBMC) and endothelial cells. IL-8 is believed to play an important role in the development of inflammation and is thus an obvious target for therapeutical modulation. We studied the possible effect of an endogenous immune modulator 1,25(OH)2-cholecalciferol (1,25(OH)2-D3) on the IL-1-induced IL-8-production by several types of cells. 1,25(OH)2-D3 inhibited the IL-1-alpha induced IL-8 production and mRNA expression in keratinocytes, fibroblasts and PBMC, but not in endothelial cells. Optimal vitamin concentrations varied between 10(-10) and 10(-11) M. These results suggest a potential role of this hormone in the regulation of chemotactic cytokine production.

Calcitriol↗
PubMed1990

The adhesiveness of monocytic U937 cells is stimulated by pro-inflammatory agents and inhibited by adenosine 3':5'-cyclic monophosphate.

We investigated the regulation of the adhesiveness of the human promonocytic cell line U-937, differentiated along the monocytic pathway either by 1,25-(OH)2-cholecalciferol or a combination of retinoic acid and dibutyryl cAMP. Adhesion to untreated polystyrene plastic was induced by inflammatory agents like PAF, fMLP or LTB4. The response to PAF first appeared after 48hr of differentiation and was inhibited by PAF antagonists and protein kinase C inhibitors indicating involvement of the phosphatidyl-inositol pathway in the stimulating effect. On the other hand, all the c-AMP raising agents tested inhibited PAF-induced cell adhesion, whatever their target membrane receptors, the Gs transducing protein, the catalytic unit of adenylate cyclase or cAMP phosphodiesterase. Direct stimulation of protein kinase A by Br8-cAMP had a similar effect. Moreover, PAF was able to increase cAMP levels. This suggests the existence of a cAMP based negative control mechanism limiting the action of PAF.

2-Chloroadenosine↗
PubMed1986

Metabolism of 25-hydroxycholecalciferol in a teleost fish, the rainbow trout (Salmo gairdneri).

Plasma concentrations of vitamin D3 (cholecalciferol) metabolites have been studied in rainbow trout (Salmo gairdneri) adapted to varying environmental calcium concentrations in both fresh water and artificial seawater, and in natural seawater. In vivo, intraarterial injection of tritiated 25-hydroxycholecalciferol was followed by its transformation to a number of metabolites including compounds that cochromatographed on high performance liquid chromatography (HPLC) with 1,25-dihydroxycholecalciferol and 25,26-dihydroxycholecalciferol. Hypercalcaemia and increased environmental calcium were associated with a greater transformation to the compound cochromatographing with 25,26-dihydroxycholecalciferol, while hypocalcaemia and reduced environmental calcium concentrations induced more conversion to the 1,25-dihydroxycholecalciferol-like compound. In vitro, both metabolites were produced by liver but not by kidney preparations, and the difference in conversion ratios observed in vivo associated with changes in plasma calcium were also seen in vitro. It is concluded that the metabolism of 25-hydroxycholecalciferol in the trout can be influenced by calcium status, but at present the physiological importance of this metabolism and the mechanisms and site(s) of action of the metabolites are unknown.

Animals↗
PubMed1976

Rickets in low birth weight infants receiving total parenteral nutrition.

Development of rickets in association with parenteral nutrition is described in four premature infants having gestational ages of 26-31 wk. In the first two infants there was a documented deficiency of vitamin D, but in the second two adequate supplementation was achieved. Vitamin D, whose primary action is to facilitate intestinal absorption of calcium, may also be a hormone of prime necessity in infant bone formation. Conversion of precursor cholecalciferol to the active form of hormone, 1,25-DHCC, requires intermediate hydroxylation by the liver. The premature infant liver may be deficient in its ability to carry out this step of metabolism, and in normal intrauterine existence the fetus may receive 1,25-DHCC, the active metabolite, from the mother. Calcium intake in these infants was far below that achieved by fetuses of comparable age in utero, even though in excess of that provided by usual premature infant oral formulas. Although calcium deficiency has not been incriminated as a cause of rickets in the past, it is possible that in very tiny premature infants rapid growth requirements lead to a relative calcium deficiency which may be manifested as uncalcified osteoid. Until the mechanism of the formation of rickets in small premature infants is clarified it is recommended that supplemental calcium and vitamin D be given to all premature infants receiving parenteral nutrition, and that periodic x-rays be obtained to detect the development of rickets.

Calcium↗
PubMed1989

Diphosphonates inhibit human osteoblast secretion and proliferation.

In view of the beneficial effect of diphosphonates in Paget's disease and their suppressive effect on alkaline phosphatase, the action of three diphosphonates (aminohydroxypropylidene diphosphonate [APD], clodronate, and didronel) on cultured human osteoblasts in vitro was investigated. All three inhibited basal and 1,25(OH)2 cholecalciferol-stimulated alkaline phosphatase secretion and [3H]thymidine uptake by osteoblasts. It is concluded that diphosphonates consistently inhibit human osteoblasts through a direct action in addition to their known effect on inhibiting bone resorption and that these actions together may form the basis of their beneficial effect in vivo in patients with Paget's disease.

Alkaline Phosphatase↗
PubMedDate not supplied

Selection of high-affinity and high-specificity monoclonal antibodies for 1 alpha,25-dihydroxyvitamin D.

The preparation of high-affinity and high-specificity monoclonal antibodies to 1 alpha,25-dihydroxyvitamin D is described. Monoclonal antibodies were derived from Balb-c mice immunised with either 1 alpha-hydroxy-25,26,27-trinor-24-cholecalcioic acid or with 1 alpha-hydroxy-26,27-dinor-cholecalciferol-25-oxime, and spleen cells were hybridised with mouse myeloma cells. From six fusions nine monoclonal antibodies (MAb's) were selected from 676 antibody-secreting hybrids. Antibodies varied widely in their ability to bind 1 alpha,25-dihydroxyvitamin D3 (50% displacement of radioligand ranged from 25 - 900 pg); two had particularly useful characteristics for 1 alpha,25-dihydroxyvitamin D assay. MAb 5F2 has high affinity (Ka = 1.39 X 10(10) M-1) and does not discriminate between 1 alpha,25-dihydroxyvitamin D2 and D3, thus enabling the two forms to be measured together. MAb 1G7 is highly specific, having no cross-reactivity with 25-hydroxy-, 24,25-dihydroxy- or 25,26-dihydroxyvitamin D at concentrations found in normal human serum; this MAb has the potential to eliminate the lengthy extraction procedures involved in currently available assays for 1 alpha,25-dihydroxyvitamin D.

Animals↗
PubMed1996

Mutation in the ligand-binding domain of the retinoic acid receptor alpha in HL-60 leukemic cells resistant to retinoic acid and with increased sensitivity to vitamin D3 analogs.

Even though retinoic acid can induce complete remissions in patients with acute promyelocytic leukemia, the duration of response is short and further therapy with this agent is less effective, suggesting the development of drug resistance. One possible way to overcome this problem is to use retinoic acid in combination with another agent that can induce differentiation, such as vitamin D3 or its analogs. In order to understand the mechanism of drug resistance to retinoic acid, we have isolated a clone of human HL-60 myeloid leukemic cells that is resistant to all-trans retinoic acid by continuous exposure to this agent. We have observed that the resistant cell line was also resistant to 9-cis-retinoic acid and more sensitive to the antileukemic action of the vitamin D3 analog, 1,25-dihydroxy-16-ene- 23-yne-26,27-F6-cholecalciferol. In addition, this combination showed synergistic antileukemic action against the wild type HL-60 leukemic cells. DNA sequence analysis revealed a mutation in the ligand binding region of retinoic acid receptor alpha in the HL-60/RA cells in which a glycine was replaced by an aspartic acid. Using gel retardation assays, we observed a large reduction in the formation of RXR-RAR heterodimers in the HL-60/RA cell line as compared to the parental cell line. This mutation in the retinoic acid receptor alpha of the HL-60/RA cells may be responsible for drug resistance to ATRA and 9-cis-retinoic acid and increased sensitivity to vitamin D3 analogs.

Antineoplastic Agents↗
PubMed1988

Alterations in histone phosphorylation in HL-60 cells specific to monocytic differentiation.

In order to examine the role of histone phosphorylation in regulation of the pathway of HL-60 cell differentiation, cells were labelled with [32P]phosphoric acid and histones fractionated by two-dimensional polyacrylamide gel electrophoresis. The monocytic inducer 12-O-tetradecanoylphorbol-13-acetate (TPA) was found to specifically stimulate phosphorylation of histone H2B in a concentration-dependent manner. At a concentration of 100 mM, H2B phosphorylation was stimulated 2.3-fold after 4 h. A second monocytic inducer 1,25-dihydroxy-cholecalciferol (100 nM) also induced phosphorylation specifically in histone H2B. In contrast, the granulocytic inducers DMSO (1.5%) or retinoic acid (1 microM) did not increase phosphorylation in any histone species.

Cell Differentiation↗
PubMed1979

A comparative study of vitamin D binding globulins in milk.

1. The occurrence of 25-hydroxy vitamin D binding protein in human, bovine, monkey and porcine milk was investigated. 2. Sucrose gradient ultracentrifugation revealed the presence of 4.2 S and 5.7 S binding globulins in the whey of human, monkey and porcine milk. 3. Although bovine plasma also contains a 4.2 S globulin only a 5.7 S protein was found in bovine milk. 4. The 4.2 S and 5.7 S globulins in milk could not be resolved by polyacrylamide gel electrophoresis or by isoelectric focusing. 5. Plasma and whey binding proteins of any one species had the same isoelectric point but there were small differences among species (4.5-4.8). 6. Competitive displacement studies showed that the binding proteins in milk have high affinity for 25-hydroxy-cholecalciferol and 24,25-dihydroxycholecalciferol.

Animals↗
PubMed1985

Effects of vitamin D metabolites on healing of low phosphate, vitamin D-deficient induced rickets in rats.

A model of low-phosphate, vitamin D-deficient rachitic rats was used to compare the effects of 1 alpha(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 on cartilage and bone. The rats were maintained for 3 weeks on a high-calcium, low-phosphate, vitamin D-deficient diet, during which period they developed severe rickets. The rachitic rats were injected for 2 or 3 consecutive days with a physiologic dose of either metabolite. Other littermates were given a single dose of 50,000 IU of cholecalciferol in combination with a normal diet. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscopic studies of the growth plate cartilage and bone. Treatment with 1 alpha (OH)D3 or with 1,25(OH)2D3, in spite of increasing Ca and P levels in the Cfl, induced only partial healing of the rickets. In contrast, 24,25(OH)2D3 or vitamin D with a normal diet resulted in complete morphologic and biochemical healing of the rickets. Transmission electron microscopic (TEM) studies have shown partial mineralization of the wide hypertrophic zone of the growth plate following treatment with 1 alpha(OH)D3 or with 1,25(OH)2D3. Mineralization was more complete with 24,25(OH)2D3 treatment. The results of this study emphasize the importance of 24,25(OH)2D3 for normal endochondral bone formation and mineralization.

24,25-Dihydroxyvitamin D 3↗
PubMed1990

Vitamin D status among patients with fractured neck of femur in Hong Kong.

Vitamin D deficiency leads to secondary hyperparathyroidism initially and then to mild osteomalacia, both of which conditions may be aymptomatic and may predispose to bone fracture. To assess the importance of vitamin D deficiency in predisposing to fractured neck of femur, we studied the vitamin D status, dietary intake and socio-economic characteristics in 69 patients with fractured neck of femur (group A), 28 normal subjects with age above 60 (group B), and 101 normal volunteers (group C). Patients with fractured neck of femor had significantly lower levels of serum 25-hydroxy-cholecalciferol compared with subjects of groups B and C. There is no statistically significant difference in other biochemical parameters, including calcium, phosphate, and alkaline phosphatase. Patients with fractured neck of femur and with 25-hydroxycholecalciferol below 20 ng/mL were characterized by a home-bound and/or institutionalized life-style, smaller living place, and limited access to open space. To conclude, hypovitaminosis D is a common problem among elderly patients with fractured neck of femur in Hong Kong. The fact that such vitamin D deficiency is associated with muscle weakness may contribute to falls, and thus indirectly account for an increased rate of hip fractures over the normal control.

Aged↗
PubMed2006

Gene expression profiling changes induced by a novel Gemini Vitamin D derivative during the progression of breast cancer.

We investigated gene expression changes induced by a novel Gemini Vitamin D(3) analog, RO-438-3582 (1alpha,25-dihydroxy-20S-21(3-hydroxy-3-methyl-butyl)-23-yne-26,27-hexafluoro-cholecalciferol, Ro3582), in a unique human breast MCF10 model. We used two breast epithelial cell lines from this model, namely MCF10AT1 (Ha-ras oncogene transfected MCF10A, early premalignant) and MCF10CA1a (fully malignant and metastatic derived from the MCF10AT1 line). We analyzed gene expression changes induced by Ro3582 using GeneChip technology, quantitative RT-PCR, Western blot analysis, or a gene transcription assay. Interestingly, we found distinct gene expression profile differences between Ro3582-induced response of the early premalignant MCF10AT1 and the malignant and metastatic MCF10CA1a cell lines. Moreover, while the Gemini Vitamin D(3) analog Ro3582 modulated the expression of several Vitamin D target genes such as the 24-hydroxylase, CD14, osteocalcin, and osteopontin in both cell lines, Ro3582 regulated many genes involved in cell proliferation and apoptosis, cell adhesion, invasion, angiogenesis as well as cell signaling pathways, such as the BMP and TGF-beta systems, differently in the two cell lines. The Gemini Vitamin D(3) analog Ro3582 induced more significant gene changes in the early premalignant MCF10AT1 cells than in the malignant metastatic MCF10CA1a cells, suggesting that Gemini Vitamin D(3) analogs may be more effective in preventing the progression of an early stage of breast carcinogenesis than in treating late stage breast cancer.

Apoptosis↗
PubMed2006

Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone.

Bisphosphonate therapy is a common and effective treatment for Paget's disease of bone, osteoporosis, hypercalcemia of malignancy and cancer metastatic to bone. Clinically significant hypocalcemia has not been reported in patients with Paget's disease of bone and normal parathyroid function treated with an aminobisphosphonate. We treated a 52-year-old woman with polyostotic Paget's disease of bone (serum alkaline phosphatase level-1971 IU/L [normal 31-110 IU/L]), who had not previously received bisphosphonates, with daily oral 30 mg risedronate, oral 1000 mg elemental calcium and oral 400 IU cholecalciferol. After 10 days of treatment, she developed severe hypocalcemia (5.4 mg/dL [normal 8.7-10.2 mg/dL]), requiring hospitalization and support with 5 days of intravenous calcium gluconate. On the day risedronate treatment began, her PTH was low normal at 14 pg/mL (normal 12-72 pg/mL), consistent with a relatively suppressed PTH axis due to high bone turnover. Her vitamin D level was within normal limits (serum 25(OH)D 19 ng/mL [normal 8-38 ng/mL]), although possibly not optimally repleted. We hypothesize that this case represents an example of hungry bone syndrome in a patient with extensive Paget's disease of bone who received risedronate, causing acute suppression of bone resorption while elevated bone formation rates continued. In the year following her recovery, the patient was successfully treated with slowly titrated anti-resorptive therapy (subcutaneous calcitonin followed by titrated doses of risedronate), and is now clinically well. Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy.

Bone Density Conservation Agents↗