중증 부갑상선 기능항진중에서 부갑상선 결절내 Calcitriol 직접 주입술 및 충격요법 병용치료의 장기간 연구결과

신석균(S. K. Shin),황재하(J. H. Hwang),송현용(H. Y. Song),노현진(H. J. Noh),최규헌(K. H. Choi),임승길(S. G. Lim),이호영(H. Y. Lee) 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.1

N/A Severe hyperparathyroidism(i-PTH>1,000pg/ml, dia-meter of nodules>1.0cm, and hypercalcemia) in dialysis patients may be resistant to conventional calcitriol- pulse therapy. To assess the usefulness of direct calcitriol injections in restoring the responsiveness to calcitriol, we performed a prospective study in 23 dialysis patients(mean age 42.3 years, M: F 0.9: 1, CGN 14, hypertension 4, lupus nephritis 2 & others 3, mean duration of dialysis 9.5 years, HD: CAPD 9: 14) who had severe hyperparathyroidism resistant to calcitriol pulse therapy for more than 2 months and had no ectopic gland in Sestamibi parathyroid scan. We three repeatedly injected calcitriol of dose(μg) equal to 3-D nodule volume(cm(3)) under U.S.(Acuson Computa Sono, California, USA, 7MHz probe) for 1 week and concurrently began calcitriol-pulse therapy(0.75-1.0μg/day, t.i.w.) after 3rd injection. All patients were followed up by serum i-FI H(Allegro Intact FPH kits, Nichols Ins.), calcium, phosphate, and U.S. after 7 days, 1 month, 6 months, and 1 year of 3rd calcitriol injection. These combination therapy could significantly decrease i-PTH level and gland volume in patients with resistant secondary hyperparathyroidism on conventional calcitriol therapy and the response were main-tained for one year after start of these therapy. The complete response group was the patients with lower baseline i-FFH levels compared to those with partial and non-response(1001.7±150.2 vs. 1521.8±328.3, 1569.2 ±344.3pg/ml, p<0.05, respectively). The patients with baseline i-PTH of less than l,200pg/ml or gland volume of less than 1.5cm were well responded to the three consecutive direct calcitriol injection and pulse combination therapy(i-PTH; PPV 77.8%, NPV 92.8%, gland volume', PPV 87.5%, NPU 93.3%). No severe adverse effect was observed during this study. In conclusion, direct calcitriol injections into the parathyroid nodules and pulse combination therapy could be useful in secondary resistant hyperparathyroidism patients with conventional calcitriol therapy especially in those with i-PTH of less than 1,200pg/ml or gland volume of less than 1.5cm. However, sugical management may be indicated in patients with higher i-PTEI levels or larger gland volume than these.

Protective Effect of Topical Vitamin D3 against Photocarcinogenesis in a Murine Model

( Ji Seok Kim ),( Min Young Jung ),( Ji Yeon Yoo ),( Eung Ho Choi ),( Byung Cheol Park ),( Myung Hwa Kim ),( Seung Phil Hong ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.3

Background: Although the incidence of non-melanoma skin cancer is increasing, there are no effective practical preventive measures other than avoiding sun exposure. Objective: To elucidate the protective effect of topical application of biologically active vitamin D3 (calcitriol) on skin cancer development caused by exposure to ultraviolet (UV). Methods: Groups of hairless mice were topically treated with either calcitriol or vehicle immediately after exposure to UVB and UVA three times weekly for the initial 20 weeks, and without UV exposure in the following 6 weeks. Tumor number was counted and biopsies were done for histopathologic analysis. The changes of cyclobutane pyrimidine dimer (CPD) were evaluated 1 hour and 11 hours after short term of UV exposure and application of calcitriol. For safety evaluation, blood test and body weights were evaluated at 23rd and 25th week. Results: Total tumor count and number of tumors less than 3 mm in size tended to be fewer in calcitriol group, and tumors more than 3 mm in size showed significantly lower tumor formation rate in calcitriol group. Single application of calcitriol reduced CPD at 1 hour and 11 hours after UV exposure. Histopathologic analysis showed tumors with lower grade malignancy in calcitriol group which suggested a delay in tumor progression. However, serum levels of calcium and phosphate in calcitriol group were above normal range, and weight loss was found. Conclusion: Topical calcitriol may suppress the formation and progression of UV-induced non-melanoma skin cancer by enhancing the repair mechanism of UV damage. (Ann Dermatol 28(3) 304∼313, 2016)

만성신부전 환자에서 Calcitriol의 PTH 억제 효과

박종원,임상우,도준영,윤경우 대한신장학회 1996 대한신장학회잡지 Vol.15 No.4

Calcitriol May Down-Regulate mRNA Over-Expression of Toll-Like Receptor-2 and -4, LL-37 and Proinflammatory Cytokines in Cultured Human Keratinocytes

( Mi Sook Jeong ),( Ji Yun Kim ),( He In Lee ),( Seong Jun Seo ) 대한피부과학회 2014 Annals of Dermatology Vol.26 No.3

Background: Although vitamin D analogs have been used in the topical treatment of psoriasis, their mechanisms of action are not well understand. Calcitriol, the hormonally active vitamin D3 metabolite, has been demonstrated to exert immunomodulatory effects in the skin by down-regulating the expression of Toll-like receptors (TLRs) and proinflammatory cytokines. Objective: We investigated the effects of calcitriol on the expression of TLR2, TLR4, antimicrobial peptide LL-37, and proinflammatory cytokines in cultured human keratinocytes. Methods: The mRNA expression levels of TLR2, TLR4, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and LL-37 in cultured human keratinocytes were measured by real-time polymerase chain reaction (PCR) and reverse transcription (RT). Furthermore, we measured supernatant TNF-α levels by an enzyme- linked immunosorbent assay (ELISA) to confirm the effects of calcitriol on TLR2 and TLR4. Results: As measured by RT-PCR and real-time PCR, calcitriol was found to suppress the lipopolysaccharide- and ultraviolet B radiation-mediated induction of expression of TLRs, LL-37 and proinflammatory cytokines such as TNF-α and IL-1β in normal human keratinocytes. The supernatant TNF-α levels measured by ELISA were also suppressed after treatment with calcitriol. Conclusion: Calcitriol may down- regulate inflammatory stated over-expression of LL-37 and proinflammatory cytokines. (Ann Dermatol 26(3) 296∼302, 2014)

Effect of additive calcium administration on FGF23 levels in patients with mild chronic kidney disease treated with calcitriol: a randomized, open-labeled clinical trial

Han, Nayoung,Hong, Su Hyun,Kim, Yon Su,Kim, Dong Ki,Kim, In-Wha,Ji, Eunhee,Oh, Jung Mi Dove Medical Press 2017 Therapeutics and clinical risk management Vol.13 No.-

<P><B>Background</B></P><P>The purpose of the present study was to determine the effect of additional calcium carbonate treatment on fibroblast growth factor 23 (FGF23) levels in patients treated with calcitriol.</P><P><B>Methods</B></P><P>In this randomized, open-labeled, and parallel-group study, a total of 30 patients with early chronic kidney disease (CKD) and vitamin D deficiency were randomly assigned to two groups and received interventions for 8 weeks: 1) a combination of calcium carbonate and calcitriol group; and 2) calcitriol only group. The primary outcome was the difference in percentage change of serum FGF23 levels from baseline between the two groups. Secondary end points included the changes in serum levels of calcium, phosphate, parathyroid hormone (PTH), and 25-hydroxyvitamin D<SUB>3</SUB> (25(OH)D) from baseline.</P><P><B>Results</B></P><P>Serum FGF23 levels were more elevated in the combination group than in the calcitriol-alone group. However, both mean change and percentage change in the serum FGF23 levels during the 8-week period were not significantly different between the two groups. Serum calcium level was increased significantly only in the combination treatment group. There was no significant difference in percentage change of serum calcium levels between the two groups. In addition, changes in serum levels of phosphate, 25(OH)D, or PTH were not significantly different between the two groups. In correlation analysis, changes in serum FGF23 levels were positively correlated with changes in serum calcium and phosphate levels, but not with changes in 25(OH)D or PTH levels. No serious adverse events were observed, however, there was one case of mild gastrointestinal discomfort.</P><P><B>Conclusion</B></P><P>This study revealed that additional calcium carbonate treatment significantly increased serum FGF23 levels in patients treated with calcitriol, with their synergistic effect in promoting intestinal calcium absorption. This suggests that serum FGF23 levels should be monitored regularly, especially in those who use combination of vitamin D and calcium carbonate from the early stages of CKD.</P>

흰쥐 십이지장 점막의 Polyamine 대사, [^(14)C]Spermine 단백 결합능 및 [³H]Thymidine DNA 섭취에 대한 Calcitriol과 Prednisolone의 상호작용

최상현,이영재,정휘정,김형건,신경호,천연숙,전보권 고려대학교 의과대학 1997 고려대 의대 잡지 Vol.34 No.1

Calcitriol has been shown to induce the duodenal synthesis of the spermine-binding protein. and hydrocortisone was reported to increase the intestinal polyamine contents. This study examined whether prednisolone might enhance or reduce the calcitriol effects on the polyamine contents, [^(14)C]spermine-protein binding activity, and [^(3)H] thymidine DNA synthesis of the rat duodenum. The mucosal contents of putrescine. spermidine. and spermine were increased by 198.8%, 84.0%, and 78.3%, respectively, within 6 hours after calcitriol. 5 ㎍/kg (CT) and fell down to the control values at 12 hours. And prednisolone. 10 mg/kg (PD) also increased the polyamine contents in similar patterns. They did not counteract each other in the polyamine metabolism. CT increased the [^(14)C]spermine-binding activity of the cytosol protein fraction from the duodenal mucosa by 71.1%. But PD increased the binding activity by 28.0% and did not affect the CT-induced increase. CT increased the [^(3)H]thymidine DNA synthesis of the duodenal mucosa by 42.3%. but PD reduced it slightly. The CT-dependent increase of the synthesis was significantly inhibited by PD. These results suggested that the inhibitory effect of glucocorticoids on the vitamin D dependent increases of the duodenal calcium absorption and mucosal proliferation seems not to be associated with the metabolic changes of polyamines in the duodenal mucosa.

Calcitriol-induced calcinosis cutis

( Kang Su Kim ),( Si Young Yang ),( Ji Eun Hahm ),( Jae Won Ha ),( Chul Woo Kim ),( Sang Seok Kim ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1

Calcinosis cutis is defined as an abnormal deposition of calcium phosphate in the skin and subcutaneous tissue. This uncommon disorder is classically divided into four subtypes: dystrophic, metastatic, idiopathic and iatrogenic. Iatrogenic calcinosis has been reported to be associated with intravenous calcium choloride or calcium gluconate therapy. We report a case of calcinosis cutis in a kidney transplant patient taking calcitriol orally. A 66-year-old female was referred to dermatology for the subcutaneous nodules on her extremities for several years. On physical examination, the patient had multiple bean sized flesh colored firm nodules on her extremities. There were no specific symptoms of itching or pain. She had right kidney transplantation in 1993 and then began to take oral calcitriol 5 years ago. Laboratory data showed a total calcium level of 9.2 mg/dL (normal range 8.4-10.2 mg/dL) and a phosphorous level of 3.6 mg/dL (normal range 2.5-4.6 mg/dL). Histophathologic findings showed basophilic-stained calcium deposits in the dermis. Black colored calcium crystals were identified in the Von Kossa stain. Therefore, she was diagnosed with calcitriol induced calcinosis cutis and discontinued calcium supplements for the treatment.

폐경 후 여성에서 Estrogen 보충요법과 병용투여된 Alendronate와 Calcitriol의 사용효과

황은정,오정미 한국병원약사회 2000 병원약사회지 Vol.17 No.4

The purpose of this study was to evaluate the effects of alendronate and calcitriol combined with hormone replacement therapy in postmenopausal osteoporotic women. Seventy-nine postmenopausal women who visited Kangnam St. Mary's Hospital were assessed to evaluate the impacts of each drug on bone mineral density and bone metabolism. Group Ⅰ was composed of 20 women who received estrogen only, Group Ⅱ was composed of 28 women who received estrogen with addition of calcitriol (0.5㎍ daily), and Group Ⅲ was composed of 31 women who received estrogen with addition of alendronate (10㎎ daily). In all subjects, bone mineral density (BMD) was measured in the lumbar vertebrae (L2-4) and femur neck using dual energy absorptiometry (DEXA), and serum osteocalcin, serum total alkaline phosphatase and urine deoxypyridinoline were measured at the beginning of the treatment and after 12 months of treatment. BMD of the lumbar vertebrae in Group Ⅱincreased significantly compared to basal level at 12 months, but not in Group Ⅰ and Ⅲ. As for BMD of the femur neck, it increased significantly during the treatment in Group Ⅰ and Group Ⅱ, but not in group Ⅲ. Serum osteocalcin in Group Ⅲ decreased significantly at 12 months of treatment compared with Group Ⅰ and Ⅱ. Serum alkaline phosphatase in Group Ⅰ and Ⅲ decreased significantly at 12 months of treatment compared with Group Ⅰ. Urine deoxyptyridinoline in Group Ⅰ, group Ⅱ and Group Ⅲ decreased but was statistically insignificant. From the above results, it might be suggested that the combined therapy (estrogen with daily addition of alendronate or calcitriol) is more effective than the estrogen therapy only for the protection of decreasing bone mineral density in the postmenopausal women.

Anti-Proliferative and Apoptotic Activities of Müllerian Inhibiting Substance Combined with Calcitriol in Ovarian Cancer Cell Lines

김영태,정연수,김희정,서석교,최영식,남은지,김성훈,김상운,한혁동,김재욱 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.1

Purpose: This study aimed to investigate whether Müllerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. Materials and Methods: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferationwere evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway. Results: The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway. Conclusion: These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatmentof OCa.

인체 각질형성세포에서 calcitriol이 지질 합성에 미치는 영향 (초)

홍승필,방승현,이상민,장성은,원종현,이미우,최지호,문기찬 대한피부과학회 2010 초록집 Vol.48 No.20