PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.
Administration, Intranasal ; Animals ; Anti-Allergic Agents ; Calcitriol ; Cell Proliferation ; Dendritic Cells ; Eosinophils ; Flow Cytometry ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Lymph Nodes ; Lymphocytes ; Major Histocompatibility Complex ; Mice ; Models, Animal ; Ovalbumin ; Ovum ; Rhinitis, Allergic ; RNA, Messenger ; Vitamin D

BACKGROUND: Bisphosphonate (BP) is an effective drug for the prevention and treatment of osteoporosis. However, gastrointestinal distress caused by BP is a well-known side effect for low compliance. The aim of our study was to compare the 1-year persistence, compliance and T-scores between the aperitif medication group and the postprandial medication group. METHODS: Three hundred patients were included in this study to determine their persistence and compliance with the prescribed daily BP (Maxmarvil®, alendronate 5 mg and calcitriol 0.5 µg; YuYu Pharm) following distal radius fractures. Patients in Group 1 (aperitif medication) were asked to adhere to the general guidelines for BPs before breakfast. Patients in Group 2 (postprandial medication) were recommended medication after breakfast. We compared the persistence and compliance of this daily BP therapy using the medication possession ratio (MPR) and T-scores between the 2 groups after 1 year. RESULTS: Bone mineral density in hip and lumbar spine was improved significantly in 2 groups (P < 0.001). Significant differences existed between 2 groups, including 73 of 150 patients (48.7%) in Group 1, and 111 of 150 patients (73.3%) in Group 2 for 1-year persistence (P=0.001). The mean MPR is 0.66 in Group 1 (range, 0.50–0.86) and 0.71 in Group 2 (range, 0.54–0.87). A significant difference was detected between the 2 groups (P=0.002). CONCLUSIONS: Postprandial administration improved persistence and compliance with daily BP therapy, resulting in better clinical outcomes.
Alendronate ; Bone Density ; Breakfast ; Calcitriol ; Compliance ; Hip ; Humans ; Osteoporosis ; Radius Fractures ; Spine

Vitamin D (VD) is essential for bone health, and VD or its analogues are widely used in clinics to ameliorate bone loss. The targets and mode of VD anti-osteoporotic actions appear to be different from those of other classes of drugs modulating bone remodeling. VD exerts its biological activities through the nuclear VD receptor (VDR)-mediated transcriptional regulation of target mRNA and non-coding RNA genes. VD-induced gene regulation involves epigenetic modifications of chromatin conformation at the target loci as well as reconfiguration of higher-order chromosomal organization through VDR-mediated recruitment of various regulatory factors. Enhancer RNAs (eRNA), a class of non-coding enhancer-derived RNAs, have recently emerged as VDR target gene candidates that act through reorganization of chromatin looping to induce enhancer-promoter interaction in activation of mRNA-encoding genes. This review outlines the molecular mechanisms of VD actions mediated by the VDR and suggests novel function of eRNAs in VDR transactivation.
Bone Remodeling ; Chromatin ; Epigenomics ; Metabolism ; Receptors, Calcitriol ; RNA ; RNA, Messenger ; RNA, Untranslated ; Transcriptional Activation ; Vitamin D ; Vitamins

Secondary hyperparathyroidism (HPT) usually result from parathyroid gland hyperplasia that produces excess parathyroid hormone (PTH). Decreased renal function leads to elevate serum phosphate levels and reduce vitamin D production, which results in hypocalcemia. Skeletal resistance to PTH results in persistently and frequently extremely elevated PTH levels and renal osteopathy. Treatment of choice for secondary HPT is medical management including calcitriol and vitamin D. However, for some cases in calciphylaxis and the failure including PTH >800 pg/mL or osteoporosis under maximal medical management surgical intervention could be an alternative option. We described a case of 47-year-old woman with surgical intervention for secondary hyperparathyroidism.
Autografts ; Calciphylaxis ; Calcitriol ; Female ; Humans ; Hyperparathyroidism, Secondary ; Hyperplasia ; Hypocalcemia ; Middle Aged ; Osteoporosis ; Parathyroid Glands ; Parathyroid Hormone ; Parathyroidectomy ; Transplantation, Autologous ; Vitamin D

PURPOSE: Despite the well-known anti-inflammatory effects of vitamin D in periodontal health, its mechanism has not been fully elucidated. In the present study, the effect of vitamin D on strengthening E-cadherin junctions (ECJs) was explored in human gingival keratinocytes (HGKs). ECJs are the major type of intercellular junction within the junctional epithelium, where loose intercellular junctions develop and microbial invasion primarily occurs. METHODS: HOK-16B cells, an immortalized normal human gingival cell line, were used for the study. To mimic the inflammatory environment, cells were treated with tumor necrosis factor-alpha (TNF-α). Matrix metalloproteinases (MMPs) in the culture medium were assessed by an MMP antibody microarray and gelatin zymography. The expression of various molecules was investigated using western blotting. The extent of ECJ development was evaluated by comparing the average relative extent of the ECJs around the periphery of each cell after immunocytochemical E-cadherin staining. Vitamin D receptor (VDR) expression was examined via immunohistochemical analysis. RESULTS: TNF-α downregulated the development of the ECJs of the HGKs. Dissociation of the ECJs by TNF-α was accompanied by the upregulation of MMP-9 production and suppressed by a specific MMP-9 inhibitor, Bay 11-7082. Exogenous MMP-9 decreased the development of ECJs. Vitamin D reduced the production of MMP-9 and attenuated the breakdown of ECJs in the HGKs treated with TNF-α. In addition, vitamin D downregulated TNF-α-induced nuclear factor kappa B (NF-κB) signaling in the HGKs. VDR was expressed in the gingival epithelium, including the junctional epithelium. CONCLUSIONS: These results suggest that vitamin D may avert TNF-α-induced downregulation of the development of ECJs in HGKs by decreasing the production of MMP-9, which was upregulated by TNF-α. Vitamin D may reinforce ECJs by downregulating NF-κB signaling, which is upregulated by TNF-α. Strengthening the epithelial barrier may be a way for vitamin D to protect the periodontium from bacterial invasion.
Bays ; Blotting, Western ; Cadherins ; Cell Line ; Down-Regulation ; Epithelial Attachment ; Epithelium ; Gelatin ; Humans ; Intercellular Junctions ; Keratinocytes ; Matrix Metalloproteinase 9 ; Matrix Metalloproteinases ; NF-kappa B ; Periodontium ; Receptors, Calcitriol ; Tumor Necrosis Factor-alpha ; Up-Regulation ; Vitamin D ; 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

Idiopathic infantile hypercalcemia is characterized by hypercalcemia, dehydration, vomiting, and failure to thrive, and it is due to mutations in 24-hydroxylase (CYP24A1). Recently, mutations in sodium-phosphate cotransporter (SLC34A1) expressed in the kidney were discovered as an additional cause of idiopathic infantile hypercalcemia. This report describes a female infant admitted for evaluation of nephrocalcinosis. She presented with hypercalcemia, hypercalciuria, low intact parathyroid hormone level, and high 1,25-dihydroxyvitamin D3 level. Exome sequencing identified novel compound heterozygous mutations in SLC34A1 (c.1337G>A, c.1483C>T). The patient was treated with fluids for hydration, furosemide, a corticosteroid, and restriction of calcium/vitamin D intake. At the age of 7 months, the patient's calcium level was within the normal range, and hypercalciuria waxed and waned. Renal echogenicity improved on the follow-up ultrasonogram, and developmental delay was not noted. In cases of hypercalcemia with subsequent hypercalciuria, DNA analysis for SLC34A1 gene mutations and CYP24A1 gene mutations should be performed. Further studies are required to obtain long-term data on hypercalciuria and nephrocalcinosis.
Calcitriol ; Calcium ; Dehydration ; DNA ; Exome ; Failure to Thrive ; Female ; Follow-Up Studies ; Furosemide ; Humans ; Hypercalcemia ; Hypercalciuria ; Hypophosphatemia ; Infant ; Kidney ; Nephrocalcinosis ; Parathyroid Hormone ; Reference Values ; Sodium-Phosphate Cotransporter Proteins ; Ultrasonography ; Vitamin D ; Vitamin D3 24-Hydroxylase ; Vomiting

Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A, OMIM 264700) is a rare autosomal recessive inherited disorder. Pathogenic variants in the CYP27B1 gene lead to loss of 1α-hydroxylase activity. We report the case of a 22-month-old toddler who presented with growth retardation and delayed development. The patient exhibited the typical laboratory findings of VDDR1A, including hypocalcemia (calcium: 5.2 mg/dL), elevated serum level of alkaline phosphatase (2,600 U/L), elevated serum level of intact-parathyroid hormone (238 pg/mL), low 1,25(OH)₂D₃ level (11.2 pg/mL), and normal 25(OH)D₃ level (40.7 ng/mL). His height and weight were 76.5 cm and 9.5 kg, respectively (both <3rd percentile). The Bayley Scales of Infant and Toddler Development II indicated significantly delayed development (mental development index <50, psychomotor development index <50). The patient was a compound heterozygous for two novel pathogenic variants in the CYP27B1 gene: c.57_69del (p.Glu20Profs*2) and c.171dupG (p.Leu58Alafs*275), inherited from his mother and father, respectively. The patient showed remarkable improvement after treatment with calcitriol and calcium carbonate.
25-Hydroxyvitamin D3 1-alpha-Hydroxylase ; Alkaline Phosphatase ; Calcitriol ; Calcium Carbonate ; Databases, Genetic ; Fathers ; Humans ; Hypocalcemia ; Infant ; Mothers ; Rickets ; Vitamin D ; Vitamins ; Weights and Measures

Adult ; Aged ; Case-Control Studies ; China ; epidemiology ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; genetics ; Middle Aged ; Polymorphism, Genetic ; Receptors, Calcitriol ; genetics ; Rural Population ; statistics & numerical data

Aged ; Case-Control Studies ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; genetics ; Exercise ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Calcitriol ; genetics ; Risk ; Rural Population