• Toxicological Research
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• 제20권3호
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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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• 제39권4호
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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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• 제8권1호
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• pp.33-42
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• 2004

목 적 : 소아 신증후군에서 스테로이드 장기투여에 따른 대사성 골질환은 흔한 합병증 중의 하나이다. 저자들은 성인에서의 스테로이드 유발성 골다공증 치료에 유효한 bisphosphonate(alendronate)를 투여하여 소아 신증후군에서 스테로이드 유발 대사성 골질환에 대한 치료효과에 대해 전향적으로 평가하고자 하였다. 방 법 : 신증후군 이환 기간이 2년된 5-8세의 환자 58명에게 DEXA로 골밀도를 측정하여 요추 골밀도가 Z-score -1 이하인 환아 30명(51.7%)을 대상으로 선정한 후 이들을 alendronate 주 1회 투여군, calcitriol 투여군, 약제 비투여군등의 세 군으로 분류하여 1년간 연구하였다. 치료 6개월, 1년에 요추 L1-L4 골밀도를 측정하였고 치료 전과 치료 1년 후 생화학적 검사를 측정하였다. 각 군간 평균 연령, 기저 요추 골밀도, 스테로이드 축적량, 골밀도% 변화율, 요추 골밀도 Z-score를 측정 분석하였다. 결 과 : 총 30명 환자에서 기본 요추 골밀도 측정시 환아의 나이는 $7.4{\pm}1.7$세였고 신증후군 이환기간은 $2.2{\pm}1.2$년이었다. Z-score로 진단된 골밀도 감소증은 23명(76.7%), 골다공증은 7명(23.3%)이었다. 각 생화학적 변수들은 치료 전후로 차이가 없었으며, 군 간에도 유의한 차이가 없었다(P>0.05). 빈번 재발형 신증후군과 스테로이드 의존형 신증후군은 22명(73.3%)으로 드문 재발형 신증후군 8명(26.6%)에 비해 대사성 골질환의 빈도가 높았다. 골밀도 변화율은 alendronate 군에서 치료 1년에 8.56%였고, calcitriol군은 5.79% 증가를 보였으며, 비투여군은 1.9%증가를 보였다. Z-socre 변화는 alendronate 군과 calcitriol 군에서만 호전되었고, 비투여군에서는 감소하였다. 골밀도 증가율은 각 군간 유의한 차이를 보였지만(P=0.0002), alendronate 군과 비투여군, calcitriol 군과 비투여군 간에 있었고(P<0.05), alendronate 군과 calcitriol 군간에는 유의한 차이가 없었다. Alendronate 투여시 약복용을 중단할 만큼의 심각한 부작용은 발현되지 않았다. 결 론 : 소아 신증후군 환자에서 고용량의 스테로이드를 투여해야 하는 경우 대사성 골질환의 발생 위험이 높기 때문에 정기적인 골밀도 측정이 필요하며, 그 평가 도구로는 요추 골밀도 Z-score가 유용함을 알 수 있었다. 또한 신증후군 환아의 스테로이드 유발 대사성 골질환에서 alendronate 주 1회 경구투여는 요추 골밀도를 증가시키는 효과적인 치료법이었다.

• Journal of Korean Neurosurgical Society
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• 제67권5호
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• pp.510-520
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• 2024

Objective : Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The treatment of PD aims to alleviate motor symptoms by replacing the reduced endogenous dopamine. Currently, there are no disease-modifying agents for the treatment of PD. Zebrafish (Danio rerio) have emerged as an effective tool for new drug discovery and screening in the age of translational research. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain, with corresponding Parkinsonian symptoms. L-type calcium channels (LTCCs) have been implicated in the generation of mitochondrial oxidative stress, which underlies the pathogenesis of PD. Therefore, we investigated the neuro-restorative effect of LTCC inhibition in an MPTP-induced zebrafish PD model and suggested a possible drug candidate that might modify the progression of PD. Methods : All experiments were conducted using a line of transgenic zebrafish, Tg(dat:EGFP), in which green fluorescent protein (GFP) is expressed in dopaminergic neurons. The experimental groups were exposed to 500 μmol MPTP from 1 to 3 days post fertilization (dpf). The drug candidates : levodopa 1 mmol, nifedipine 10 μmol, nimodipine 3.5 μmol, diethylstilbestrol 0.3 μmol, luteolin 100 μmol, and calcitriol 0.25 μmol were exposed from 3 to 5 dpf. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized in vivo by confocal microscopy. Results : Levodopa, nimodipine, diethylstilbestrol, and calcitriol had significant positive effects on the restoration of motor behavior, which was damaged by MPTP. Nimodipine and calcitriol have significant positive effects on the restoration of dopaminergic neurons, which were reduced by MPTP. Through locomotor analysis and dopaminergic neuron quantification, we identified the neuro-restorative effects of nimodipine and calcitriol in zebrafish MPTP-induced PD model. Conclusion : The present study identified the neuro-restorative effects of nimodipine and calcitriol in an MPTP-induced zebrafish model of PD. They restored dopaminergic neurons which were damaged due to the effects of MPTP and normalized the locomotor activity. LTCCs have potential pathological roles in neurodevelopmental and neurodegenerative disorders. Zebrafish are highly amenable to high-throughput drug screening and might, therefore, be a useful tool to work towards the identification of disease-modifying treatment for PD. Further studies including zebrafish genetic models to elucidate the mechanism of action of the disease-modifying candidate by investigating Ca2+ influx and mitochondrial function in dopaminergic neurons, are needed to reveal the pathogenesis of PD and develop disease-modifying treatments for PD.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.161.1-161.1
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• 2001

• Biotechnology and Bioprocess Engineering:BBE
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• 제11권5호
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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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• 제23권3호
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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.

• 보건행정학회지
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• 제11권3호
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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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• 제17권5호
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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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• 제50권11호
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• pp.1129-1133
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• 2007

골화석증은 뼈파괴세포의 기능의 이상과 백혈구의 과산화물 생성 이상을 특징으로 하는 드문 골경화성 질환으로, 유전방법이나 발병나이, 증상, 증상의 정도 등에 따라 몇 가지 아형으로 분류된다. 악성형 골화석증의 궁극적 치료 방법은 조혈모세포이식이지만, 조직형 일치 공여자가 없는 경우나 비교적 양성인 만성형 골화석증에서는 스테로이드나 carcitriol, 인터페론 감마 등의 치료를 시도해 볼 수 있다. 특히 인터페론 감마 치료는 골흡수를 증가시키고, 조혈 기능과 백혈구 기능을 향상시킨다고 보고되고 있다. 본 저자들은 약 6년, 3년 동안 인터페론 감마 치료 후 각각 수혈, 골절과 같은 다른 합병증 없이 조절되고 있는 골화석증 2례에 대해 보고하는 바이다.