Microglia are activated by inflammatory and pathophysiological stimuli in neurodegenerative diseases, and activated microglia induce neuronal damage by releasing cytotoxic factors like nitric oxide (NO). Activated microglia synthesize a significant amount of vitamin D3 in the rat brain, and vitamin D3 has an inhibitory effect on activated microglia. To investigate the possible role of vitamin D3 as a negative regulator of activated microglia, we examined the effect of 25-hydroxyvitamin D3 on NO production of lipopolysaccharide (LPS)-stimulated microglia. Treatment with LPS increased the production of NO in primary cultured and BV2 microglial cells. Treatment with 25-hydroxyvitamin D3 inhibited the generation of NO in LPS-activated primary microglia and BV2 cells. In addition to NO production, expression of 1-alpha-hydroxylase and the vitamin D receptor (VDR) was also upregulated in LPS-stimulated primary and BV2 microglia. When BV2 cells were transfected with 1-alpha-hydroxylase siRNA or VDR siRNA, the inhibitory effect of 25-hydroxyvitamin D3 on activated BV2 cells was suppressed. 25-Hydroxyvitamin D3 also inhibited the increased phosphorylation of p38 seen in LPS-activated BV2 cells, and this inhibition was blocked by VDR siRNA. The present study shows that 25-hydroxyvitamin D3 inhibits NO production in LPS-activated microglia through the mediation of LPS-induced 1-alpha-hydroxylase. This study also shows that the inhibitory effect of 25-hydroxyvitamin D3 on NO production might be exerted by inhibiting LPS-induced phosphorylation of p38 through the mediation of VDR signaling. These results suggest that vitamin D3 might have an important role in the negative regulation of microglial activation.
Animals ; Brain ; Calcifediol* ; Cholecalciferol ; Microglia* ; Negotiating ; Neurodegenerative Diseases ; Neurons ; Nitric Oxide* ; Phosphorylation ; Rats ; Receptors, Calcitriol ; RNA, Small Interfering

This research was conducted to examine the effect of cholecalciferol on fasting blood glucose (FBG), adipocyte diameter and glucose transporter (GLUT) 4 expression in adipocytes of diabetic rats. Nineteen male Wistar strain diabetic rats were divided into 4 groups (K, X1, X2 and X3). Cholecalciferol was administered in the amount of 6.25 μg/kg in X1, 12.5 μg/kg in X2 and 25 μg/kg in X3 per orem, once daily for 14 days. Group K received the placebo. There were no significant differences in FBG (p=0.199) and adipocyte diameter (p=0.218) between groups but there were significant differences in the expression of GLUT4 between control and treatment groups. Thus, cholecalciferol can increase GLUT4 expression in adipocyte without altering FBG and adipocyte diameter of diabetic rats.
Cholecalciferol ; Adipocytes

BACKGROUND/AIMS: The exact relationship between vitamin D deficiency and inflammatory bowel disease (IBD) remains unclear. We evaluated the effect of vitamin D3 administration on inflammatory responses and disease severity in patients with IBD. METHODS: We investigated the serum 25-hydroxyvitamin D3 [25-(OH)D], C-reactive protein (CRP) levels and the partial Mayo score (PMS) in patients with IBD. Vitamin D3 was administered in patients with either vitamin D deficiency or insufficiency and CRP, serum vitamin D levels and PMS were re-examined at 6 months of administration. RESULTS: In 88 patients with Crohn's disease (CD), a negative correlation was found between serum vitamin D and CRP. In 178 patients with ulcerative colitis (UC), serum vitamin D showed no association with CRP or PMS. Serum vitamin D increased from 11.08±3.63 to 22.69±6.11 ng/mL in 29 patients with CD and from 11.45±4.10 to 24.20±6.61 ng/mL in 41 patients with UC who received vitamin D3 treatment (P<0.001 and P<0.001, respectively). In patients with CD, median ΔCRP was –0.24 in the normalized vitamin D group and –0.11 in the non-normalized group (P=0.308). In patients with UC, median ΔCRP was −0.01 in the normalized vitamin D group and 0.06 in the non-normalized group (P=0.359). CONCLUSIONS: Although a negative correlation was found between serum vitamin D and CRP levels in patients with CD, administration of vitamin D did not improve the CRP level in patients with CD. In patients with UC, serum vitamin D level was unrelated to CRP or PMS.
C-Reactive Protein ; Calcifediol ; Cholecalciferol ; Colitis, Ulcerative ; Crohn Disease ; Humans ; Inflammatory Bowel Diseases ; Vitamin D Deficiency ; Vitamin D ; Vitamins

PURPOSE: It is well known that obesity is related to vitamin D deficiency (VDD). We investigated the response to vitamin D replacement in normal-weight and overweight children. METHODS: This was a prospective study including 62 Korean children with VDD. VDD was defined as a serum 25-hydroxycholecalciferol (25(OH)D) concentration <20 ng/mL. Overweight was defined as a body mass index (BMI)≥the 85th percentile (n=21), and normal weight as a BMI between the 5th and 84th percentiles (n=41). All participants received vitamin D3 supplementation (2,000 IU/day) for 8 weeks. The serum levels of 25(OH)D, PTH and biochemical parameters were measured before and after treatment. RESULTS: The mean age was 10.0±1.4 years in normal-weight children and 10.0±2.1 years in overweight children (P=0.93). After 8 weeks of treatment, 61.9% of normal-weight children and 47.6% of overweight children achieved vitamin D sufficiency (P =0.30). The mean serum 25(OH)D levels after vitamin D replacement were 33.8±7.6 ng/mL and 30.3±6.6 ng/mL in normal-weight and overweight children, respectively (P =0.10). The mean calcium/creatinine ratios after treatment were 0.09±0.07 and 0.08±0.06 in the normal-weight and overweight groups, respectively, and no hypercalciuria was found. In multiple regression analysis, the response to vitamin D replacement was influenced by the BMI (β=-1.0, P=0.03) and sex (β=-4.0, P=0.04). CONCLUSIONS: Eight weeks of vitamin D replacement (2,000 IU/day) is sufficient to overcome vitamin D deficiency in normal-weight and overweight children without any complications.
Body Mass Index ; Calcifediol ; Child ; Cholecalciferol ; Humans ; Hypercalciuria ; Obesity ; Overweight ; Prospective Studies ; Vitamin D Deficiency ; Vitamin D ; Vitamins

The cutaneous synthesis of vitamin D in response to ultraviolet radiation exposure is the most important factor in maintaining vitamin D balance in Man. The skin is not only the site of vitamin D synthesis, but also a target organ for calcitriol(1, 25-dihydroxy-vitamin D) which is naturally occuriag, hormonally active form of vitamin E. It is now known that calcitriol inhibits the proliferation of epidermal cells and induces her differentiation. In this study, epidermal keratinocytes and melanocytes were isilated from the neonatal foreskin, and were culturod using a MCDB 153 and modified TIC media, respectively. And then various concentratioris of calcipotriol(MC 903), a synthetic aralogue of calcitriol, were added to each culture. The effects of calcipotriol on the growth of human keratinocytes and melanocytes were investigated. The results were as follows : 1. The addition of calopotriol to human keratinocyte and melalocyte cultures inhibited their proliferation in a dosdependent manner. 2. Calcipotriol had no effects on the melanization process of the melanocyte. 3. Calcipotriol was found to inhibit the proliferation, however it induced the terminal differentiation of cultured keratinocytes, as judged by morphologicai changes. The decreased density of kerationcytes, The formation of cornified cells, and the cellular destruction in a concentration of 10 M of calcipotriol were observed. 4. By using the light atid the electron microscope, we observed that the epidermal thickness was decreased and terminal differentiation was facilitateir. Living Skin Equivalent (LSE) according to the increasing concentration of calcipotriol. A]i)parent cytotoxic effects were observed in 10 M, 10 M of calcipotriol. In summary, the above results indicate that the addition of calcipotriol to the in vitro culture system of human keratinocyte and melanocyte induces the biologic process of terminal differentiation of keratinocytes and inhibits proliferation of keratinoytes and melanocytes in a dose-dependent manner.
Calcitriol ; Cholecalciferol* ; Foreskin ; Humans* ; Keratinocytes* ; Melanocytes* ; Skin ; Tics ; Vitamin D ; Vitamin E ; Vitamins*

Bone is a dynamic tissue which is constantly remodelled by subsequent cycles of bone resorption and formation. Glucocorticoid and vitamine D3 are known as regulating substances in bone metabolism. In vitro experiments using bone tissue, it was suggested that glucoccorticoid inhibits bone resorption, whereas the effect of glucocorticoid on bone formation are complex- increasing or decreasing effect. The active form of vitamin D3, 1,25-dihydroxycholecalciferol [1.25-(OH)2D3], has been reported to stimulate osteoblastic activities including the production of ALP, type I collagen, and osteoclacin. The purpose of this study was to evaluate the effect of admixture of vitamin D3 and dexamethasone, one of glucocorticoids, on osteblastic cell line(MC3T#-E1). Alkaline phosphatase(ALP) and MTT assay were conducted in the cultivated cells with 1, 10, 100nm/ml of 1,25-(OH)2D3 and/or 10nM/ml, 100nM/ml, 1micrometer/ml of dexamethasone. The observed results were as follows. 1. The activity of osteoblastic cells with 1micrometer/ml of dexamethasone was significantly increased at 1-day cultivation with comparison to control group, but was decreased afterwards. But the activity of ALP was greatest in 1micrometer/ml of dexamethasone and increased with time lapsed. 2. The activity of osteoblastic cells with vitamin D3 was significantly increased dose-dependently at 1-day cultivation, but was significantly decreased in 10nM/ml or 100nM/ml at 2-day or 3-day cultivation, and was greatest in 100nM/ml at 3-day cultivation. 3. In case of admixture of dexamethasone and vitamin D3 at 2-day cultivation, but was increased again at 3-day cultivation, which was greater than that in control or dexamethasone only group. The activity of ALP was decreased at 1-day cultivation, but was increased in the admixture of 10nM/ml or 100nM/ml of dexamethasone with 100nM/ml of vitamin D3 at 2-day cultivation, and was again decreased at 3-day cultivation.
Bone and Bones ; Bone Resorption ; Calcitriol ; Cholecalciferol ; Collagen Type I ; Dexamethasone* ; Glucocorticoids ; Metabolism ; Osteoblasts* ; Osteogenesis ; Vitamins*

Hypersensitivity to cholecalciferol (vitamin D3) or its active metabolite, calcitriol, is an exceedingly rare clinical phenomenon, with only 2 previously reported cases of suspected immediate hypersensitivity. Diagnosis of delayed drug hypersensitivity reactions is inherently difficult due to the lack of any robust in vitro diagnostic assay, particularly in those patients for whom provocation testing confers an unacceptable risk. In these situations, diagnosis relies on reproducible clinical manifestations following administration of the culprit agent, resolution upon its withdrawal and exclusion of other potential differential diagnoses. Based on these criteria, we propose the first reported case of delayed hypersensitivity to cholecalciferol successfully managed with a desensitisation protocol to pure cholecalciferol.
Calcitriol ; Cholecalciferol ; Diagnosis ; Diagnosis, Differential ; Drug Hypersensitivity ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Hypersensitivity, Immediate ; In Vitro Techniques

BACKGROUND: It is still unclear the ideal vitamin D dosage once the deficiency and insufficiency is treated. Once deficiency was corrected we prospectively treated patients with 2,000 IU of vitamin D3 to check whether this dosage is enough to keep them above the 30 ng/mL of 25-hydroxy-vitamin D (25[OH]D). METHODS: One hundred and thirty-five Saudi Arabian men and women treatment naïve for the vitamin D deficiency and insufficiency were part of this study. History and clinical examination were done to rule out any metabolic bone disease. Weight and height was taken to calculate the body mass index (BMI). Patients who were vitamin D deficient (≥30 ng/mL), a standard treatment of 50,000 IU of vitamin D3 weekly for 3 months, a blood test for the vitamin D levels at the end of 3 months, maintenance dose of 2,000 IU of vitamin D3 for 3 months and a third blood sample after 3 months. RESULTS: The data for 128 patients was available for analysis. The average age was 44.95±12.97 years with the mean BMI of 29.60±2.59 kg/m2. The baseline 25(OH)D level was 13.16±3.30 ng/mL. The increase in the level of 25(OH)D on 50,000 IU weekly was significant from 13.16±3.3 ng/mL to 36.97±4.67 ng/mL (P < 0.001) and then 2,000 IU daily for next 3 months, the level of 25(OH)D dropped top 20.38±5.42 ng/mL (P < 0.001). CONCLUSIONS: Our study indicates that the maintenance dose of 2,000 IU of vitamin D is not enough for patients to keep the 25(OH)D levels above 30 ng/mL.
Body Mass Index ; Bone Diseases, Metabolic ; Calcifediol ; Cholecalciferol ; Dietary Supplements ; Female ; Hematologic Tests ; Humans ; Male ; Prospective Studies ; Vitamin D Deficiency ; Vitamin D* ; Vitamins*

Pseudohypoparathyroidism (PHP) is a rare clinical type of hypoparathyroidism. The patients with PHP show classic clinical and biochemical features of hypoparathyroidism, but elevated serum level of parathyroid hormone (PTH) and characteristic physical appearances termed 'Albright's hereditary osteodystrophy' (AHO). PHP is classified into types Ia, Ib, Ic and II according to the presence of AHO phenotype and the mechanism of PTH resistance. We experienced a case of PHP in a 12 year-old girl with carpopedal spasm, syncope and partial AHO. She showed very low serum calcium level (1.4 mmol/L), high phosphorus level (3.62 mmol/L) and high immunoreactive PTH level (186.6 ng/L). In the Ellsworth-Howard test, urinary cyclic adenosine monophosphate and phosphorus levels after an exogenous PTH injection remained unchanged. Therefore, we were able to classify the patient as either PHP type Ia or Ic. After the patient had been treated with daily calcium carbonate (1 g), cholecalciferol (250 IU) and calcitriol (0.5 microgram), her neurological signs and symptoms as well as her biochemical abnormalities of hypocalcemia and hyperphosphatemia were improved.
Adenosine Monophosphate ; Calcitriol ; Calcium ; Calcium Carbonate ; Child ; Cholecalciferol ; Female ; Humans ; Hyperphosphatemia ; Hypocalcemia ; Hypoparathyroidism ; Parathyroid Hormone ; Phenotype ; Phosphorus ; Pseudohypoparathyroidism* ; Spasm ; Syncope

Pseudohypoparathyroidism (PHP) is a rare clinical type of hypoparathyroidism. The patients with PHP show classic clinical and biochemical features of hypoparathyroidism, but elevated serum level of parathyroid hormone (PTH) and characteristic physical appearances termed 'Albright's hereditary osteodystrophy' (AHO). PHP is classified into types Ia, Ib, Ic and II according to the presence of AHO phenotype and the mechanism of PTH resistance. We experienced a case of PHP in a 12 year-old girl with carpopedal spasm, syncope and partial AHO. She showed very low serum calcium level (1.4 mmol/L), high phosphorus level (3.62 mmol/L) and high immunoreactive PTH level (186.6 ng/L). In the Ellsworth-Howard test, urinary cyclic adenosine monophosphate and phosphorus levels after an exogenous PTH injection remained unchanged. Therefore, we were able to classify the patient as either PHP type Ia or Ic. After the patient had been treated with daily calcium carbonate (1 g), cholecalciferol (250 IU) and calcitriol (0.5 microgram), her neurological signs and symptoms as well as her biochemical abnormalities of hypocalcemia and hyperphosphatemia were improved.
Adenosine Monophosphate ; Calcitriol ; Calcium ; Calcium Carbonate ; Child ; Cholecalciferol ; Female ; Humans ; Hyperphosphatemia ; Hypocalcemia ; Hypoparathyroidism ; Parathyroid Hormone ; Phenotype ; Phosphorus ; Pseudohypoparathyroidism* ; Spasm ; Syncope