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At least 217 records · Page 12Linked to original sources
PubMed1983

Improvement of the absorption of 3H-Cholecalciferol by formation of its cyclodextrin complex.

Following oral administration to rats of beta-cyclodextrin inclusion complex of 3H-labelled vitamin D3 (cholecalciferol) resulted in significantly higher blood radioactivity as with the non-complexed vitamin. Difference in the first 90 min was 2,3-2,8 fold, and it remained significantly higher up to the 6th h. After 24 h there was no difference between the blood radioactivity of animals treated with complexed and with non-complexed vitamin D3.

Cholecalciferol↗
PubMed2003

Chemical reactivity of Ro-26-9228, 1alpha-fluoro-25-hydroxy-16,23E-diene-26,27-bishomo-20-epi-cholecalciferol in aqueous solution.

The degradation of Ro-26-9228, 1alpha-fluoro-25-hydroxy-16,23E-diene-26,27-bishomo-20-epi-cholecalciferol, 2, was studied in aqueous solution in the pH range of 1.17-10.56 and in alcohol solutions, at 25, 40, and 50 degrees C. The degradation of Ro-26-9228 was found to be acid catalyzed and to be independent of potassium acetate buffer concentration. Above pH 4, the reaction rate is independent of pH, with a T90 of 14.3 h at 25 degrees C in pH 7.75 buffer. 19F nuclear magnetic resonance was used to study the ratio of the vitamin (6-s-trans) to previtamin form in acetonitrile at 40 degrees C. The equilibrium percentage of previtamin and the rate of approach to equilibrium were 13.8% and 0.2 h(-1), respectively. Nuclear magnetic resonance was used to elucidate the structure of the degradation products. Novel products were formed from the elimination of the fluorine and addition of solvent to C9, with formation occurring through the previtamin form. Additional degradation products result from reaction of the side chain 25-hydroxyl and addition of solvent to C1.

2-Propanol↗
PubMed1998

Differentiation-related pathways of 1 alpha,25-dihydroxycholecalciferol metabolism in human colon adenocarcinoma-derived Caco-2 cells: production of 1 alpha,25-dihydroxy-3epi-cholecalciferol.

We used the human colon adenocarcinoma-derived cell line Caco-2, which spontaneously differentiates in vitro, as a model system to investigate the metabolism of 1 alpha,25-dihydroxycholecalciferol in colon cancer cells. Subconfluent proliferating and confluent differentiating cells were incubated with 1 microM 1 alpha,25-dihydroxycholecalciferol for a period of 24 to 48 h. HPLC analysis of the lipid extract of both cells and media was performed to isolate and identify the various metabolites of 1 alpha,25-dihydroxycholecalciferol. Undifferentiated, highly proliferating Caco-2 cells metabolized 1 alpha, 25-dihydroxycholecalciferol into several side chain modified metabolites formed through the C-24 oxidation pathway. In contrast, no metabolites of the C-24 oxidation pathway were identified in differentiated Caco-2 cells. However, differentiated cells produced significant amounts of a metabolite which was less polar than 1 alpha, 25-dihydroxycholecalciferol on a straight phase HPLC system. This metabolite was identified as 1 alpha,25-dihydroxy-3alpha-cholecalciferol by comigration with a synthetic standard on two different HPLC systems and gas chromatography--mass spectrometry. Thus, we were able to demonstrate that the state of differentiation has a profound influence on 1 alpha,25-dihydroxycholecalciferol metabolism in colon cancer cells.

Alkaline Phosphatase↗
PubMed2003

Efficacy and mechanism of action of 1alpha-hydroxy-24-ethyl-cholecalciferol (1alpha[OH]D5) in breast cancer prevention and therapy.

It is now well established that the active metabolite of vitamin D3, 1alpha,25(OH)2D3, regulates cell growth and differentiation in various in vitro cancer models. However, its clinical use is precluded due to its hypercalcemic activity in vivo. Hence, several less calcemic vitamin D analogs have been synthesized and evaluated for their chemopreventive and therapeutic efficacy in experimental carcinogenesis models. A novel analog of vitamin D3, 1alpha-hydroxy-24-ethyl-cholecalciferol (1alpha[OH]D5), has currently been under investigation in our laboratory for its application in breast cancer prevention and therapy. 1alpha(OH)D5 had been shown to inhibit development of estrogen- and progesterone-dependent ductal lesions as well as steroid hormone-independent alveolar lesions in a mammary gland organ culture (MMOC) model. Moreover, the inhibitory effect was more significant if 1alpha(OH)D5 was present during the promotional phase of the lesion development. The growth inhibitory effect of 1alpha(OH)D5 has also been manifested in several breast cancer cell lines, including BT-474 and MCF-7. Breast cancer cell lines that responded to 1alpha(OH)D5 treatment were vitamin D receptor positive (VDR+). Vitamin D receptor-negative (VDR-) cell lines, such as MDA-MB-231 and MDA-MB-435, did not show growth inhibition upon incubation with 1alpha(OH)D5. This suggests the requirement of VDR in 1alpha(OH)D5-mediated growth effects. Interestingly, breast cancer cells that were VDR+ as well as estrogen receptor positive (ER+) showed cell cycle arrest and apoptosis, while VDR+ but ER- cells (UISO-BCA-4 breast cancer cells) showed enhanced expression of various differentiation markers with la(OH)D5 treatment. Transcription and expression of estrogen-inducible genes, progesterone receptor (PR) and trefoil factor 1 (pS2), were significantly down-regulated in ER+ BT-474 cells with 1alpha(OH)D5 treatment. This implies a differential effect of 1alpha(OH)D5 on ER+ vs. ER- cells. Additionally, comparison between the effects of 1alpha(OH)D5 on normal vs. transformed cells indicated that 1alpha(OH)D5 does not suppress cell prolifera-

Animals↗
PubMed1997

1.25(OH)2 cholecalciferol pulse therapy and the effects of different dialysis membranes on serum PTH levels of haemodialysis patients.

Either oral, intravenous or subcutaneous 1.25(OH)2 cholecalciferol is used in the therapy of hyperparathyroidism, which is a serious complication in patients on haemodialysis. We studied a total of 30 patients (10 women and 20 men) and divided them into two groups depending on the different types of dialysis membranes used. In the polysulfone group, mean age was 43.7 +/- 0.97 years and the average dialysis period lasted 29.9 +/- 1.23 months. For the 15 cases in which we used cuprophane membrane the mean age was 40.2 +/- 1.31 years and the average dialysis period lasted 16.2 +/- 0.86 months. The calcium level of the dialysate in both groups was 1.5 mmol/l. According to the study protocol, the determined oral calcitriol dose was 0.07 mg/kg and it was administered intermittently. After one month on high dose calcitriol therapy, treatment was continued with a maintenance dose of 0.03 mg/kg for a further six months. As a phosphate binding agent, daily 3 g calcium carbonate was administered. Before starting this treatment protocol, patients went on a 1 mg/day calcitriol therapy, although the mean PTH level was 424.63 pg/ml and the mean serum alkaline phosphatase level was 290.2 U/l. During the pretreatment period, levels of PTH, alkaline phosphatase, ionized calcium, and total calcium remained significantly within normal limits as a result of the new therapy protocol applied. PTH and phosphorus clearance rates were compared in the patient groups in which different dialysis membranes had been used. PTH and phosphorus clearances were 15.2 +/- 3 ml/min and 239.1 +/- 19.2 ml/min, respectively, in the polysulfone membrane group, and 1.1 +/- 0.3 ml/min and 112.8 +/- 9.88 ml/min, respectively, in the cuprophane membrane group (p < 0.05).

Adult↗
PubMed1983

Tissue and subcellular distributions of cholecalciferol 25-hydroxylase: cytochrome P-450D25-linked monooxygenase system.

Cholecalciferol (vitamin D3) 25-hydroxylase activity and its tissue and subcellular distributions were studied using rabbit, rat, bovine, chick, duck, guinea-pig and yellowtail. Vitamin D3 25-hydroxylase was found not only rabbit and bovine livers, kidneys and intestines, but also in lungs, pituitary glands, adrenocortices, ovaries, adipose tissues, blood vessels, brains and testes. Subcellular fractions of rabbit livers were examined for the presence of this activity and it was detected in the nuclear membranes, smooth and rough endoplasmic reticula, Golgi membranes and mitochondrial membranes. The activity in microsomes was induced by sodium phenobarbital, but not by beta-naphthoflavone and 3-methylcholanthrene, and was inhibited by isocyanide and metyrapone as inhibitor of cytochrome P-450.

Animals↗
PubMed1996

Sarcoidosis causes abnormal seasonal variation in 1,25-dihydroxy-cholecalciferol.

OBJECTIVES: The spontaneous seasonal variations in the calcium regulating hormones 1,25-dihydroxy-cholecalciferol (1,25-DHCC) and parathyroid hormone (PTH) were investigated in patients with sarcoidosis. DESIGN: Controlled, prospective observational study with measurements in the winter and summer seasons, respectively. SUBJECTS: Twelve patients (age: median 33, range 21-54 years) with biopsy-verified (n = 8) sarcoidosis were included as well as 11 age-matched healthy control subjects. MAIN OUTCOME MEASURES: Serum values of calcium, ionized calcium, phosphate, chloride, bicarbonate, creatinine, albumin, angiotensin-converting enzyme, alkaline phosphatase, 1,25-DHCC, and PTH. Also, 24-h whole body retention of 99mTc methylene-diphosphonate was assessed. RESULTS: The patient group showed an increased level of 1,25-DHCC in the summer season (w:146 +/- 67, s:198 +/- 73 pmol L-1; P < 0.01) in contrast to the opposite finding among controls (w:161 +/- 34, s:144 +/- 43 pmol L-1; P < 0.05). Comparing the individual seasonal changes between the two groups, the difference was marked (P < 0.001). Compared with controls, total serum calcium was elevated in the summer season in the patient group (P < 0.05), in which the same parameter correlated positively with 1,25-DHCC (r = 0.658; P < 0.01). PTH was increased two to three times above the control values throughout the year (patients: w:0.37 +/- 0.13, s:0.24 +/- 0.08 micrograms L-1; controls: w:0.14 +/- 0.09, s:0.10 +/- 0.04 micrograms L-1; P < 0.001); although, the level of this hormone was still found within the reference interval. 24-h whole body bone scintigraphy failed to show any seasonal variation in bone metabolism. In contrast, serum alkaline phosphatase was found to be increased during the summer season compared with the control group (P < 0.001). Angiotensin-converting enzyme showed no seasonal variation. CONCLUSIONS: In sarcoidosis, 1,25-DHCC is abnormally regulated throughout the year, with a significantly higher serum level in the summer season. Uncontrolled production of 1,25-DHCC in sarcoid pulmonary alveolary macrophages is possibly responsible for hypercalcaemic episodes, and this parameter should be used as a marker of disease activity.

Adult↗
PubMed2000

Influence of parathyroid hormone, calcitonin, 1,25(OH)2 cholecalciferol, calcium, and the calcium ionophore A23187 on erythrocyte morphology and blood viscosity.

Parathyroid hormone and calcitonin, both endocrine modulators of calcium homeostasis, may influence blood rheology. Parathyroid hormone is known to reduce erythrocyte survival, leading to anemia. Calcitonin has been found to have some vascular effects. We have analyzed the Influence of parathyroid hormone (10(-7) to 10(-10) mol/L), calcitonin (10(-6) to 10(-12) mol/L), 1,25(OH)2 cholecalciferol (10(-7) to 10(-10) mol/L), additional calcium in plasma (+1 and 2 mmol/L), and the calcium lonophore A23187 (50 micromol/L) on erythrocyte morphology and blood viscosity at high shear rate (94 s(-1)) and low shear rate (0.1 s(-1)) in vitro. The loading of erythrocytes with calcium by the ionophore A23187 produced a marked echinocytic shape transformation, an increased blood viscosity at high shear rate caused by decreased deformability of these cells, and a decreased viscosity at low shear rate caused by decreased aggregation of echinocytes. In contrast, increasing plasma calcium concentrations, parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D3 had no effect on erythrocyte morphology and blood viscosity. We conclude that an increase in intraerythrocytic calcium leads to severe echinocytosis and altered blood viscosity. The endocrine modulators of calcium homeostasis--namely, parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D3--apparently do not influence intraerythrocytic calcium to a significant degree and have, therefore, no influence on cell morphology and blood viscosity.

Blood Viscosity↗
PubMed1981

Nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in dispersed fibroblasts cultured from normal human skin.

Because of the relative inaccessibility of known calciferol target tissues (i.e., intestine and bone), we examined fibroblasts derived from normal human skin and grown in tissue culture as a means of evaluating the interaction of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its effector system. When dispersed, intact cells were used, nuclear uptake of 1,25-dihydroxy[23,24(n)3-H]cholecalciferol [1,25(OH)2[3H]D3) was temperature-dependent, optimal at 45 min at 37 degrees C, and saturable. In competition experiments with other calciferols, the 1,25(OH)2[3H]D3 uptake showed specificity indistinguishable from that reported for 1,25(OH)2D3 receptors from calciferol target tissues. Analysis of 1,25(OH)2[3H]D3 nuclear uptake in fibroblast strains from six normal adults (four male, two female) yielded an average binding capacity (R0) of 10,600 +/- 2,000 (SEM) nuclear sites per cell and an apparent dissociation contant (Kd) of 0.50 +/- 0.07 (SEM) x 10(-9) M. Donor sex, donor age, or anatomic site of origin of the cell line did not affect the characteristics of uptake. Similar nuclear uptake was demonstrable with cultured MCF-7 cells (derived from human breast cancer) when assayed in the same fashion. When hypertonic extracts of nuclei obtained from skin fibroblasts incubated with 1,25(OH)2[3H]D3 were subjected to centrifugation on sucrose gradients, a single peak of radioactivity sedimented at approximately 3 S; when excess 1,25(OH)2D3 was coincubated during the cellular uptake phase, this 3S peak was not observed. Molybdate was an essential buffer component for receptor stabilization during cell fractionation and sedimentation analysis. In summary, by using fibroblasts cultured from normal human skin, we have identified a process of nuclear uptake of 1,25(OH)2[3H]D3 with the affinity, saturability, and specificity characteristics of a steroid hormone--receptor interaction. This method should be useful in studying 1,25(OH)2D3 recept physiology in cells from normal persons as well as in cells from patients who have disorders in the responsiveness of calciferol target tissues.

Biological Transport↗
PubMed1985

Cholecalcin (a 9-kDa cholecalciferol-induced calcium-binding protein) messenger RNA. Distribution and induction by calcitriol in the rat digestive tract.

In view of the possible physiological importance of the 9-kDa cholecalcin (a 9000-Mr cholecalciferol-induced calcium-binding protein) in the intestinal transport of calcium in mammals, the gene expression of this protein has been analysed. Its regulation in the digestive tract of the growing rat by calcitriol (1,25-dihydroxycholecalciferol) was studied using a specific cloned [32P]cDNA to 9-kDa cholecalcin. Northern hybridisation studies show that the cDNA sequence hybridises to a single 500-600-nucleotide species throughout the digestive tract and therefore demonstrate identical 9-kDa-cholecalcin mRNA processing in the whole of the intestine and caecum. The highest concentrations of cholecalcin mRNA occur in the duodenum, proximal jejunum and caecum. The observed differences in 9-kDa-cholecalcin mRNA levels correlate well with both the in vivo variations in cholecalcin itself and with the known intestinal sites of calcium absorption. The whole intestine is able to respond to exogenous calcitriol but the response of the distal intestine and caecum, as measured by the increase in cholecalcin mRNA and corresponding protein, was proportionally higher than in the duodenum. The rapid production of fully functional cholecalcin mRNA, which was detectable as early as 1 h after a single dose of calcitriol to vitamin-D-deficient rats, provides convincing evidence that calcitriol increases 9-kDa cholecalcin production by increasing cholecalcin gene expression at the transcriptional level.

Animals↗
PubMed1984

Premature cranial synostosis in X-linked hypophosphatemic rickets: possible precipitation by 1-alpha-OH-cholecalciferol intoxication.

A child suffering from X-linked hypophosphatemic rickets developed vitamin D intoxication under treatment with 1-alpha-OH-cholecalciferol (1(OH)D3) and phosphorus. Beside the usual findings in this condition he showed precocious synostosis of the skull with signs of raised intracranial pressure. In view of earlier reports of coincidence of craniostenosis and X-linked hypophosphatemic rickets, we conclude that the possibility exists that intoxication with 1(OH)D3 has been the precipitating factor. In addition we found hypersensitivity to 1(OH)D3 2 months after cessation of treatment, and normal levels of calcitriol (1,25(OH)2D3) at the same time.

Cranial Sutures↗
PubMed1976

Use of 1alpha-OH cholecalciferol in preventing post parturient hypocalcaemia and its potential value for the prevention of milk fever in dairy cows.

Cows which received 250 mug 1alpha-hydroxy cholecalciferol (1alpha-OH D3) intramuscularly within two hours after calving suffered significantly less post-parturinet hypocalcaemia and hypophosphataemia than control cows. There was a small depression in plasma magnesium concentrations in the treated cows. 1alpha-OH D3 shows potential for the prevention or treatment of milk fever.

Animals↗
PubMed1985

1-Alpha-OH-cholecalciferol (1-alpha-OH-D3) and optimal calcium intake in calcium deficiency osteoporosis mediated by parathyroid activity morphologic and biochemical changes in adult male rats.

By feeding adult male rats a calcium deficient diet for a period of 6 weeks osteoporosis can be induced with respect to significant changes in mass, turnover, chemical composition, and morphology of bone and parathyroid glands. When subsequently treating the osteoporotic rats with a combination of 1-alpha-OH-cholecalciferol (1-alpha-OH-D3) and optimal calcium intake osteoporosis as well as morphologic changes of parathyroids can be almost totally reversed as soon as after 2 weeks and completely after 4 and 6 weeks. Notwithstanding the change to an optimal calcium intake seems to be more important in normalizing the osteoporotic skeleton resulting from calcium deficiency than is the ingestion of 1-alpha-OH-D3, which may per se induce new bone formation.

Animals↗
PubMed1980

Effect of 1 alpha-hydroxy-cholecalciferol and varying phosphorous content in the diet on calcium phosphorous metabolism in hypokinetic rats.

Hypokinesia induces mineral changes, including changes in calcium and phosphorus metabolism, which involve their increased renal excretion, deposition in soft tissues, and development of osteoporosis. These experiments were designed in order to ascertain the role of active metabolites (hydroxy-cholecalciferol) and changes in phosphorus in the diet on calcium accumulation in bone, soft tissue, and renal calcinosis, and changes in calcium-phosphorus metabolism in rats during prolonged and severe hypokinesia.

Animals↗
PubMed2000

Influence of cholecalciferol (vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice.

The course of systemic lupus erythematosus (SLE), an autoimmune disease, is markedly affected by hormones such as estrogen and prolactin. It is well known that heavy exposure to sunlight has deleterious effects on SLE, triggering episodes of the disease. Classical explanations for this occurrence suggest that UV radiation damages DNA, which becomes immunogenic, or induces exposure of the Ro antigen in keratinocytes. In recent years, it has been shown that vitamin D3 has important effects on the immune system. Thus, we proposed an alternative hypothesis, suggesting that UV radiation, by promoting vitamin D3 synthesis, could be a factor aggravating the course of SLE after exposure to sunlight. To test this hypothesis, we injected F1(NZBxW) mice, which are prone to developing SLE, with vitamin D3, and we demonstrated a worsening of the histopathological findings in the kidney.

Animals↗