• Toxicological Research
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• v.20 no.3
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• pp.281-292
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• 2004

The purpose of this study was to assess the single and 5 week oral dose toxicity of calcitriol and alendronate combination (1 : 10,000) treatment for osteoporosis or Paget's disease in male and female rats. In single dose oral toxicity study, the values of $LD_{50}$ of calcitriol and alendronate mixture were 750.075 mg/kg in male rats and 775.0775 mg/kg in female rats, respectively. Body weight and food consumption were continuously increased after adminstration of calcitriol and alendronate mixtures, and there was no significant changes in body weight and food consumption in all groups. In five-week oral toxicity study of calcitriol and alendronate mixture at a dose of 0.2 $\mu\textrm{g}$ + 2 mg, 1 $\mu\textrm{g}$ + 10 mg, 5 $\mu\textrm{g}$ + 50 mg and 25 $\mu\textrm{g}$ + 250 mg, respectively, there was no mortality, abnormal behavior and appearance in all groups throughout the administration period (5 weeks) and recovery period (2 weeks). Dose-dependent changes in parameters of urinalysis and hematological analysis were not observed in male and female rats treated with calcitriol and alendronate mixtures. All the values of the parameters appeared to be in the normal range. These data indicate that both calcitriol and alendronate are drugs having low toxicity in rats. NOAEL of calcitriol and alendronate mixtures were 50.005 mg/kg in 5-week oral toxicity.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.309-314
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• 2009

An enzyme immunoassay (EIA) was validated for quantitation of cacitriol in human plasma. Calcitriol was immunoextracted with immunocapsules, which contain monoclonal antibodies to calcitriol linked to solid phase particles in suspension with a vitamin D binding protein inhibitor. Calcitrol was eluated and the eluates were evaporated under a gentle stream of nitrogen gas. The absorbance of analytes was determined using a microplate reader (reference wavelength 650 nm; measurement wavelength 450 nm). The method was specific and sensitive enough to detect as low as 6.5 pmol/L of calcitriol. Linear calibration range was 6.5-491 pmol/L with correlation coefficient greater than 0.99. The overall accuracy was in the range of 83.8 to 111.2% and precision C.V. (%) 0.99 to 8.47%. The recovery was approximately 100% and stability was confirmed during storage and sample preparation. The pharmacokinetic parameters were calculated by baseline subtraction because calcitriol is an endogenous material. Following oral dose of calcitriol, the mean AUC$_{24h}$ was 1038${\pm}$539 pmol/Lhr and C$_{max}$ of 128${\pm}$63.1 pmol/L was reached at 3.50${\pm}$1.07 hr. The mean t$_{1/2}$ of calcitriol was 5.13${\pm}$2.10 hr. The present EIA method was successfully applied to study bioavailability after oral administration of 2 ${\mu}$g of calcitriol in healthy Korean subjects.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.33-42
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• 2004

Purpose : Children with nephrotic syndrome(NS) are under high risk for metabolic bone disease(MBD) as a complication of long-term glucocorticoid therapy. We prospectively evaluated the effect of oral bisphosphonate(alendronate) therapy in children with NS, which has proven efficacy in adult patients with glucocorticoid induced MBD. Methods : Among 58 children with NS, aged 5 to 8 years and haying a disease duration of more than 2 years, 30(51.7%) were enrolled to meet the selection criteria, less than -1.0 Z-scores of lumbar spine bone mineral density(BMD) by dual energy X-ray absorptiometry (DEXA). These 30 children were divided into three groups and each were assigned to receive alendronate, calcitriol, and no-medication, respectively for one year. Lumbar spine BMD was followed up every 6 months and the biochemical indexes were measured before and 1 year after the treatment. There were no significant difference among groups with respect to the average age, the initial BMD, and the cumulative steroid doses. Analysis of the treatment efficacy was done by the % change of BMD and by the changes in Z-scores of lumbar spine BMD. Results : Mean age and disease duration of patients at the initial lumbar spine BMD evaluation was $7.4{\pm}1.7$ years and $2.2{\pm}1.2$ years, respectively. Twenty-three of 30 children(76%) had osteopenia, and seven(23%) had osteoporosis. There was no difference in the biochemical values among the groups, before and 1 year after the treatment(P<0.05). Twenty two children(73.3%) with frequent relapsing or steroid dependant NS had more frequent MBD, compared to the 8 children(26.6%) with infrequent relapsing NS. The one year % changes of BMD were 8.56 in alendronate group, 5.79 in calcitriol group, and 1.9 in no-medication group. The changes in Z-score of lumbar spine BMD increased in the alendronate group and the calcitriol group, but not in the no-medication group. One year % changes of BMD were different among groups(P=0.0002). Significant differences were found between the alendronate and the no-medication group, and between the calcitriol and the no-medication group(P<0.05). There was no difference between the alendronate and the calcitriol group. No serious adverse effect was observed in the alendronate group. Conclusion : Children with NS receiving high dose steroids are under the high risk of BMD and should undergo regular BMD evaluation. Z-score of lumbar spine BMD was a useful parameter in diagnosing low bone mass in children. Alendronate weekly oral therapy was effective and relatively safe in increasing the lumbar spine BMD in children with NS having steroid induced MBD.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.161.1-161.1
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• 2001

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.5
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• pp.408-413
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• 2006

We assessed the ability of a Pseudonocardia sp. from soil samples to bioconvert vitamin $D_3$. The optimal culture conditions for the bioconversion of vitamin $D_3$ to active $1{\alpha}$,25-dihydroxyvitamin $D_3$ were investigated by varying the carbon and nitrogen sources, the metal salt concentrations, the initial pH, and the temperature. Microbial transformations were carried out with the addition of vitamin $D_3$ dissolved in ethanol. They were sampled by extraction with methanol-dichloromethane and the samples were examined by HPLC. Optimum culture conditions were found to be 0.4% yeast extract, 1% glucose, 3% starch, 1% fish meal, 0.2% NaCl, 0.01% $K_2HPO_4$, 0.2% $CaCO_3$, 0.01% NaF, and pH 7.0 at $28^{\circ}C$. The optimal timing of the addition of vitamin $D_3$ for the production of calcitriol by Pseudonocardia autotrophica ID9302 was concurrent with the inoculation of seed culture broth. Maximum calcitriol productivity and the yield of bioconversion reached a value of 10.4mg/L and 10.4% respectively on the 7th day in a 75L fementer jar under the above conditions.

• Archives of Pharmacal Research
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• v.23 no.3
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• pp.206-210
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• 2000

A new series of phosphonate side chain analogues of 1$\alpha$,25-dihydroxyvitamin $D_3$ (1) have been synthesized. Antiproliferative activities of theses analogues (8a,b and 9a,b) using human keratinocyte cell shows that analogues which have natural A-ring show higher activity than unnatural A-ring series and almost equally active to 1 $\alpha$,25-Dihydroxyvitamin $D_3$(1) at 1 $\mu$M level.

• Health Policy and Management
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• v.11 no.3
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• pp.71-88
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• 2001

The purpose of this study is to analyze the cost-effectiveness of four medications for treating and preventing osteoporosis -HRT therapy(conjugated equine estrogen 0.625mg for 25 days and medroxyprogesterone acetate 5mg for 01112 days), Alendronate(10mg and 5mg), Active Vitamin D(Calcitriol), and Calcium. Total costs include the direct medical cost -examination fee, consultation fee, prescription fee, fee for preparing medications, and the price of pharmaceuticals- and the indirect cost of patients such as traffic expenses and time cost. In addition, the costs of monitoring in adverse reactions are added. The effects of four medications are expressed as BMD(Bone Mineral Density) percent change measured by DEXA(Dual Energy X-ray Absorptiometry) in lumbar spine(L2-L4) and femoral neck site. A mixed model based on meta analysis provides the estimates of effectiveness, which are then appled to the hypothetical cohort consisting of postmenopausal women at the age of 50-59. HRT therapy is the most cost-effective medication at 172,433.64 won (lumbar spine site) and 546,328.28 won (femoral neck site) per BMD percent change for osteoporosis. Alendronate 10mg is more cost-effective than Alendronate 5mg as 345,971.23 won and 378,441.63 won per lumbar BMD percent change at 0.991ｇ/$cm^2$, respectively. Alendronate 10mg is more cost-effective than Alendronate 5mg as 1,329,257.89 won and 1,467,291.23 won per femoral neck BMD percent change at 0.834ｇ/$cm^2$, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.385-392
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• 2013

Vitamin D deficiency is prevalent, primarily due to limited sun exposure, which may be observed in urban areas, or as a result of modern lifestyles. Common myths about vitamin D persist, including that it is mostly obtained from the diet and is only essential for bone and mineral homeostasis. Nonetheless, advances in biomedical science suggest that vitamin D is a hormone that is integral to numerous physiologic functions in most cells and tissues. Therefore, abnormal vitamin D levels may contribute to health disturbances. A number of recent reports on potential associations between vitamin D deficiency and cardiovascular disease have highlighted its role in this system. A focus over the previous decade has been to better understand the mechanisms behind vitamin D regulation and the pathophysiology associated with suboptimal vitamin D levels. Vitamin D deficiency is highly associated with the incidence of cardiovascular diseases, even when considering other well-known risk factors. In this process, the renin-angiotensin system is disrupted, and hypertension and endothelial dysfunction contribute to the risk of cardiovascular disease. Likewise, clinical outcomes upon the normalization of vitamin D levels have been investigated in different patient populations. It makes sense that vitamin D supplementation to improve vitamin D status among vitamin D-deficient individuals could be useful without requiring a sudden lifestyle change. This manuscript provides a brief overview of vitamin D metabolism and the vitamin D receptor. It also summarizes the current clinical research relating to vitamin D supplementation and its effects on hypertension and endothelial dysfunction in cardiovascular medicine.

• Clinical and Experimental Pediatrics
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• v.50 no.11
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• pp.1129-1133
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• 2007

Osteopetrosis, a rare osteosclerotic bone disease characterized by a defect in osteoclast function and the reduced generation of superoxide by leukocytes, can be classified into several types based on their mode of inheritance, age of onset, severity, and associated clinical symptoms. Stem cell transplantation is the only curative therapy for the infantile malignant type, although alternative treatments, such as corticosteroids, calcitriol, and interferon (IFN)-${\gamma}$ have been attempted in patients with milder clinical types. In addition, IFN-${\gamma}$ therapy has been reported to increase bone resorption and hematopoiesis and to improve leukocyte function. Here, we present the cases of two patients with osteopetrosis who benefited from either 3 or 6 years of INF-${\gamma}$ therapy that resulted in improved blood counts and no further pathological fractures.

• Journal of Veterinary Clinics
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• v.31 no.3
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• pp.216-219
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• 2014

An 1-year-old, female, mixed-breed dog weighing 17 kg was referred for abrupt collapse. She had remarkable hypocalcemia and hyperphosphatemia, and survey radiographs revealed a severe gas-filled intestine. Treatment with serial injections of calcium gluconate was initiated promptly and most of the gastrointestinal distension disappeared after 4 h. However, the clinical signs were not resolved completely. The serum intact parathyroid hormone concentration was not elevated in the context of hypocalcemia, which suggested primary hypoparathyroidism. The clinical signs and laboratory abnormalities in the patient were resolved completely 3 days after administration of calcium gluconate and calcitriol. This case describes the unique presentation of severe gastrointestinal distension in a dog diagnosed with primary hypoparathyroidism.