OBJECTIVE: To determine the effects of multivitamin vitamin D 300 or 600 units on serum 25 hydroxyvitamin D (25(OH)D) level after 4 weeks of supplementation in postmenopausal women with vitamin D insufficiency. STUDY DESIGN: Randomized double-blind, placebo-controlled trial. METHODS: Postmenopausal women who had vitamin D insufficiency were recruited into the study. The participants were randomized to 3 groups of 4-week treatment period with multivitamin (GPO, Governmental Pharmacy Organization) 2 tablets (contained vitamin D2 amount 600 units), multivitamin 1 tablet (contained vitamin D2 amount 300 units) or placebo. At baseline and after 4 weeks of supplementation, serum 25(OH)D were determined with electrochemilumines-cence immunoassay (Cobas, Roche Diagnostics) and level change of 25(OH)D level were compared among the groups. RESULTS: Out of 144 participants, 49.3% had vitamin D deficiency (<20 ng/ml) and 50.7% had vitamin D insufficiency (<30 ng/ml). However, after 4 weeks of the GPO oral multivitamin, serum 25(OH)D levels significantly increased from 19.4 ± 6.3 ng/ml at baseline to 22.2 ± 5.2 ng/ml (P = 0.01) and from 19.5 ± 5.0 ng/ml to 23.3 ± 5.2 ng/ml (P < 0.01) in the groups receiving vitamin D 300 IU and 600 IU/day, respectively. Approximately, 10% of those who took vitamin D had serum 25(OH)D level above the insufficiency level within 4 weeks. There was no significant changes of serum 25(OH)D after 4 weeks in the placebo group. CONCLUSION: Daily supplementation of the generic multivitamin containing vitamin D2 300 and 600 IU daily for 4 weeks significantly increased mean serum 25(OH)D from baseline up above the deficiency level.
Ergocalciferols ; Female ; Humans ; Immunoassay ; Pharmacy ; Postmenopause ; Tablets ; Vitamin D Deficiency ; Vitamin D* ; Vitamins*

Maxillary enlargement is a rare complication of secondary hyperparathyroidism (SHPT). A 35-year-old Korean man undergoing chronic hemodialysis presented with a painless enlargement involving the maxilla and mandible. Plain radiography and CT scan showed bony expansion at the maxilla and mandible with multiple radiolucency. Serum intact parathyroid hormone (iPTH) was >1,600 pg/mL. Tc-99m sestamibi (MIBI) parathyroid scan and neck sonogram were compatible with SHPT. He underwent limited parathyroidectomy and commenced a course of paricalcitol. Fifteen months after surgery, maxillary enlargement and bony resorptions involving both hands markedly improved. Thirty-six months after the surgery, the serum iPTH level was 109.3 pg/mL. This is the first report in Korea documenting a patient with maxillary enlargement in SHPT who was successfully treated with limited parathyroidectomy and paricalcitol.
Adult ; Ergocalciferols ; Hand ; Humans ; Hyperparathyroidism ; Hyperparathyroidism, Secondary ; Korea ; Mandible ; Maxilla ; Neck ; Parathyroid Hormone ; Parathyroidectomy ; Renal Dialysis ; Renal Osteodystrophy

BACKGROUND: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin E₂ (PGE₂) receptor EP4. METHODS: Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/mL) for 1 hour and exposed to LPS (1 μg/mL). The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA) were investigated. RESULTS: The expression of cyclooxygenase-2, PGE₂, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB) were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. CONCLUSION: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.
Apoptosis* ; Cell Death ; Cyclooxygenase 2 ; Cytokines ; Ergocalciferols ; Humans ; Inflammation* ; Phosphorylation ; Receptors, Prostaglandin E, EP4 Subtype ; RNA, Small Interfering ; Vitamin D

While the anti-apoptotic effect of paricalcitol has been demonstrated in various animal models, it is not yet clear whether paricalcitol attenuates the apoptosis in gentamicin (GM)-induced kidney injury. We investigated the effect of paricalcitol on apoptotic pathways in rat kidneys damaged by GM. Rats were randomly divided into three groups: 1) Control group (n=8), where only vehicle was delivered, 2) GM group (n=10), where rats were treated with GM (150 mg/kg/day) for 7 days, 3) PARI group (n=10), where rats were co-treated with paricalcitol (0.2 microg/kg/day) and GM for 7 days. Paricalcitol attenuated renal dysfunction by GM administration in biochemical profiles. In terminal deoxynucleotidyl transferase dUTP nick end labeling staining, increased apoptosis was observed in GM group, which was reversed by paricalcitol co-treatment. Immunoblotting using protein samples from rat cortex/outer stripe of outer medulla showed increased Bax/Bcl-2 ratio and cleaved form of caspase-3 in GM group, both of which were reversed by paricalcitol. The phosphorylated Jun-N-terminal kinase (JNK) expression was increase in GM, which was counteracted by paricalcitol. The protein expression of p-Akt and nitro-tyrosine was also enhanced in GM-treated rats compared with control rats, which was reversed by paricalcitol co-treatment. Paricalcitol protects GM-induced renal injury by antiapoptotic mechanisms, including inhibition of intrinsic apoptosis pathway and JNK.
Acute Kidney Injury* ; Animals ; Apoptosis ; Caspase 3 ; DNA Nucleotidylexotransferase ; Ergocalciferols ; Gentamicins ; Immunoblotting ; Kidney* ; Models, Animal ; Phosphotransferases ; Rats

PURPOSE: Vitamin D deficiency is reported to be more common in type 1 diabetes patients and might be associated with the increased urinary loss of vitamin D binding protein (VDBP) consequent to impaired 25-hydroxyvitamin D (25(OH)D) circulation. We aimed to evaluate the possible increased urinary loss of VDBP, a correlation between VDBP and circulating 25(OH)D level, and risk factors influencing low vitamin D level in pediatric type 1 diabetes patients without microalbuminuria. METHODS: This is a cross-sectional study of subjects who visited Seoul National University Children’s Hospital between January and March 2013. Forty-two type 1 diabetes patients and 29 healthy controls were included. Biochemical parameters including serum and urine VDBP concentrations were analyzed. RESULTS: There was no significant difference in the frequency of vitamin D deficiency or serum 25(OH)D level between the 2 groups. The serum and urine VDBP concentrations did not show any difference between the 2 groups. Serum 25(OH) D level did not correlate with serum or urine VDBP. Multivariate regression analysis revealed that daylight outdoor hours (β=2.948, P=0.003) and vitamin D intake (β=2.865, P=0.003) affected the 25(OH)D level; the presence of type 1 diabetes or urinary VDBP excretion was not significant. CONCLUSIONS: In pediatric type 1 diabetes patients, urinary VDBP excretion did not contribute to low serum 25(OH)D level in the setting of normoalbuminuria. The factors associated with 25(OH)D level during winter periods were daylight outdoor hours and vitamin D intake. Further studies including both micro- and macroalbuminuria patients with type 1 diabetes are warranted.
Albuminuria ; Child ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1 ; Ergocalciferols ; Humans ; Risk Factors ; Seoul ; Vitamin D ; Vitamin D Deficiency ; Vitamin D-Binding Protein* ; Vitamins*

Secondary hyperparathyroidism is a major complication in ESRD patients undergoing dialysis. In hemodialysis patients with secondary hyperparathyroidism, intravenous administration of paricalcitol became widely utilized. In CAPD patients, however, the intravenous administration of paricalcitol which requires frequent visits to the clinic is not practical. The subject of this study was one CAPD patient with secondary hyperparathyroidism. He had already received oral calcitriol pulse therapy for 6 months and thereafter refused parathyroidectomy and intravenous paricalcitol which required frequent visits to the hospital. Furthermore, paricalcitol capsule is not yet introduced in Korea. Consequently, intraperitoneal paricalcitol therapy was tried whereby the patient was taught how to inject the paricalcitol (5 ug) directly into the dialysate for three times per week before bedtime. Blood samples for measurement of intact parathyroid hormone (iPTH), serum ionized calcium, serum phosphate, serum total alkaline phosphatase levels were obtained at baseline and after 1, 2, 3 and 4 months of treatment. After usage of intraperitoneal paricalcitol for 2 months, there was a significant decrease in iPTH level. In conclusion, intraperitoneal paricalcitol therapy might be effective for suppressing iPTH in CAPD patients with secondary hyperparathyroidism. A large-scale and long-term study must be conducted for safety and clinical effect.
Administration, Intravenous ; Alkaline Phosphatase ; Calcitriol ; Calcium ; Dialysis ; Ergocalciferols ; Humans ; Hyperparathyroidism, Secondary ; Injections, Intraperitoneal ; Kidney Failure, Chronic ; Korea ; Parathyroid Hormone ; Parathyroidectomy ; Peritoneal Dialysis, Continuous Ambulatory ; Renal Dialysis

Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic??hematologic, (6) inflammatory-oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 microg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.
Cardio-Renal Syndrome ; Dialysis ; Ergocalciferols ; Heart ; Heart Diseases ; Hemodynamics ; Humans ; Kidney Diseases ; Parathyroid Hormone ; Receptors, Calcitriol ; Renal Insufficiency, Chronic ; Vitamin D ; Vitamins

No abstract available.
Adult ; Aged ; Asian Continental Ancestry Group/ethnology ; China ; Cholecalciferol/*analysis ; Ergocalciferols/*analysis ; Female ; Humans ; Immunoassay ; India ; Malaysia ; Male ; Middle Aged ; Reagent Kits, Diagnostic ; Young Adult

In this work a system which consists of chitosan (CS) microcores entrapped within enteric polymer is presented. Vitamin D2, used as a model drug, was efficiently entrapped within CS microcores using spray-drying and then microencapsulated into ethylic cellulose(EC). The morphology and release properties of microcapsules were tested. The influential factors of preparation conditions included molecular weight of chitosan, concentration of chitosan solution, concentration of acetic acid, loading of vitamin D2 were discussed. The results of in vitro release studies showed that the microcapsules prepared in this article could realize sustained release in intestine.
Capsules ; Cellulose ; analogs & derivatives ; pharmacology ; Chitin ; analogs & derivatives ; pharmacology ; Chitosan ; Delayed-Action Preparations ; Drug Compounding ; Drug Delivery Systems ; Ergocalciferols ; pharmacology ; In Vitro Techniques

Vitamin D is present in two forms, ergocalciferol (vitamin D2) produced by plants and cholecalciferol (vitamin D3) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D], plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of 1,25(OH)2D from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the 1alpha-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D 1alpha-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of 1,25(OH)2D despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human 1alpha-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and 1alpha-hydroxylase mutations with clinical findings.
Animals ; Biology ; Bone Development ; Calcitriol ; Calcium ; Cholecalciferol ; Clone Cells ; Cloning, Organism ; Dehydrocholesterols ; Ergocalciferols ; Humans ; Hydroxylation ; Hypocalcemia ; Kidney ; Liver ; Muscle Hypotonia ; Parathyroid Hormone ; Receptors, Calcitriol ; Rickets ; Seizures ; Skin ; Ultraviolet Rays ; Vitamin D ; Vitamins