쿠싱증후군 환자에서 당 대사 이상 정도에 따른 인슐린 감수성과 인슐린 저항성의 변화

정인경,김성훈,정재훈,민용기,이명식,이문규,유형준,안규정,노정현,김동준,김광원 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경 당질 코르티코이드는 당 대사에 매우 중요한 호르몬으로 내인성 당질 코르티코이드 과다상태인 쿠싱증후군에서는 말초조직에서 인슐린 저항이 증가하고 이를 보상하고자 인슐린 분비의 증가로 고인슐린혈증이 동반된다고 보고되고 있다. 하지만 생체 내에서와 달리 시험관내에서는 췌도세포에 당질 코르티코이드를 장시간 처리하면, 인슐린 분비 및 생합성이직접적으로 억제됨이 확인된 바 있어 쿠싱증후군 환자에서 당뇨병의 원인으로는 아마도 말초조직에서 증가된 인슐린 저항성 뿐 아니라 이를 충분히 보상하지 못하는 췌장에서의 인슐린 분비 저하가 같이 동반되어있지 않을까 하는 가설을 세우게 되었고, 아직까지 당질코르티코이드가 당대사 이상을 일으키는 기전에 대해 쿠싱증후군을 당대사 정도에 따라 인슐린 감수성과 분비능을 분석한 연구는 없었기에 이를 알아보고자 하였다. 방법: 삼성서울병원에서 쿠싱증후군으로 진단 받은 환자 15명을 대상으로 하였다. 이에 대한 대조군으로는 쿠싱증후군 환자와 같은 성별 그리고 체질량지수를 갖은 15명의 건강한 성인을 대상으로 비교 하였다 쿠싱증후군 환자를 대상으로 경구당부하 검사를 통해 당대사 정도를 정상군, 내당능장애군, 그리고 당뇨병군으로 나눈 후 정맥 당부하 검사를 시행하여 각군의 인슐린 저항성과 인슐린 분비능의 지표를 비교하고, 수술 후 쿠싱증후군이 완치된 상태에서 수술 전후의 당대사 지표의 변화를 조사하였다. 결과: 1) 쿠싱증후군 환자 중 정상인은 20%, 내당능 장애는 27%, 그리고 당뇨병은 53%였다. 체질량지수, 나이, 그리고 발병 기간은 세 군간에 의미 있는 차이가 없었으나, 24시간 소변검사의 코르티솔 농도는 당뇨병군에서 의미있게 높았다. 2) 정맥당부하 검사 결과, 인슐린 감수성 지표인 Sl는쿠싱증추린」서 1.58±0.10[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 대조군의 3.37±0.49[×10^(-4)(min^(-1)(μU/mL)^(-1)]에 비해 의미있게 낮았으나(P=0.024), 쿠싱증후군 환자 중 NGT, IGT, DM 군간에 서로 통계적인 차이는 없었다. 3) SG는 정상 대조군과 쿠싱증후군 환자간에는 의미있는 차이가 없었고, 쿠싱 증후군에 있어서 당대사가 악화될수록 감소하는 경향을 보였으나 의미있는 차이는 없었다. 4) 인슐린 분비능의 지표인 AIRg는 정상인에 비해 전체 쿠싱증후군 환자의 경우 증가하는 경향을 보였으나 의미있는 차이는 없었다. 하지만 쿠싱증후군 환자중에서 당대사 상태에 따라 NGT군은 1299 (1297∼1310)(mu/g/min ×10^(-2))로 정상 대조군(368.9±98.6[mu/g/min ×10^(-2)]) 보다도 의미있게 높았고, DM군{202.2 (91.1~371.4) [mu/g/min ×10^(-2)}은 NGT군에 비해 의미있게 낮았다(P=0.0031). 5) 15명중 현재 완치 상태에 있는 6명에 대해 수술전과 후로 비교하였다. 수술 전 당대사 상태가 1명은정상, 1명은 내당능 장애, 그리고 4명은 당뇨병이었으나 수술 후 시행한 경구 당부하 검사상 모두 정상 당대사 상태를 보였다. 6) 수술 후 완치된 환자 6명에 있어 인슐린 감수성지표인 Sl는 수술전에 중앙값이 1.22[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 대조군에 비해 의미있게 감고』어 있었으나(p.0.05), 수술후 10.95 [×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 수준으로 회복되었고(P=0.0022), 인슐린 분비능을 나타내는 AIRg [mu/g/min ×10^(-2)] 값도 정상수준으로 회복되었다. 특히 인슐린 분비능의 회복양상은 혈당농도에 따라 판이하게 나타나서, 정상과 내당능장애 상태에 있던 2명은 수술전에 1201 [mu/g/min ×10^(-2)]로 증가되어 있던 AIRg 값이 수술 후 정상 수준으로 감소하였고, 수술 전에 당뇨병 상태에 있던 4명의 경우 245.9 [mu/g/min ×10^(-2)]로 인슐린 분비능이 감고il어 있었는데 이들은 수술 후 모두 정상 수준으로 증가되었다 (P=0.0286). 결론: 쿠싱증후군 환자에서 당대사 이상은 80%로 높은 유병률을 보였다. 모든 쿠싱증후군환자에서 인슐린 감수성은 정상인에 비해 저하되어 있어 말초조직의 인슐린 저항이 선행됨을 시사하며, 인슐린 분비능은 당대사의 정도에 따라 다르게 나타났는데, 정상 당대사군에서는 인슐린의 저항성을 극복할 만큼 정상 대조군보다 더 많은 양의 인슐린 분비를 하다가 고코르티솔혈증이 심할수록 인슐린 분비능의 감소로 당뇨병으로 진행됨을 확인할 수 있었고, 이런 인슐린 저항성과 인슐린 분비장애는 수술 후 다시 회복되는 가역적인변화를 보였다. Background: Glucocorticoid plays an important role in the control of carbohydrate metabolism. Patients with Cushing's syndrome have been reported to have an increased incidence of carbohydrate intolerance due to peripheral insulin resistance and hyperinsulinemia, although the exact incidence and nature of this disorder have remained unclear. Few results have been published about insulin resistance and insulin secretion according to the level of glucose concentration, or about the reversibility of such defects in patients with Cushing's syndrome. Methods: To assess the effect of glucocorticoid on the insulin sensitivity and insulin secretion in Cushing's syndrome, 15 patients with Cushing's syndrome were classified into 3 groups (normal glucose tolerance: NGT, impaired glucose tolerance: IGT, diabetes: DM) according to the degree of glucose tolerance based on the oral glucose tolerance test (OGTT). Insulin modified, frequently sampled, intravenous glucose tolerance test (FSIGT) was performed before and after curative surgery on these patients and on 15 healthy control subjects. Data were evaluated by non-parametric statistical analysis. Results: 1) Among the 15 patients with Cushing's syndrome, 3 (20%) were NGT, 4 (27%) IGT, and 8 (53%) DM, based on OGTT. Twenty-four hour urinary free cortisol (UFC) was significantly higher in the DM group. 2) Insulin sensitivity index (SI) of Cushing's syndrome was significantly lower than that of the control group p=0.0024), but was not significantly different among the three Cushing's syndrome groups of NGT, IGT and DM. 3) Glucose mediated glucose disposal (SG) (Ed- confirm this abbreviation; it does not seem to match the definition) of Cushing's syndrome was not significantly different from that of the control group. 4) Insulin secretion (AIRg) of Cushing's syndrome tended to be high, but it was not significantly different from that of control. However, according to the level of glucose concentration there was significant difference in AlRg among the three Cushing's syndrome groups p=0.0031); AIRg of DM was significantly lower than that of NGT. 5) After surgical treatment, parameters of insulin sensitivity and insulin secretion were normalized in 6 cured patients; 1 with NGT, 1 with IGT, and 4 with DM, preoperatively. Median SI of all 6 patients was significantly improved up to the normal range postoperatively p=0.0022). Median AIRg of these 6 patients was balanced around that of normal control postoperatively p=0.0286). Conclusion: Eighty percent of patients with Cushing's syndrome had abnormality of carbohydrate metabolism. Insulin sensitivity was significantly decreased in Cushing's syndrome. Insulin secretion was significantly higher only in the NGT and IGT groups of Cushing's syndrome. As the hypercortisolemia is exacerbated, insulin secretion is significantly decreased and causes DM, suggesting that glucocorticoid has a direct or indirect toxic effect on the pancreatic beta cell (J Kor SOC Endocrinol 18:392-403, 2003).

가열 조건을 달리한 단호박 페이스트와 검 종류별 단호박 라떼의 품질특성

박보람,김나정,유선미,한귀정,김하윤,한혜민,신동선,신말식,Park, Bo-ram,Kim, Na-Jung,Yoo, Seon-Mi,Han, Gwi Jung,Kim, Ha Yoon,Han, Hye-min,Shin, Dong-Sun,Shin, Malshick 한국식품조리과학회 2015 한국식품조리과학회지 Vol.31 No.3

가열 조건에 따른 단호박 페이스트를 제조하기 위해, 단호박을 15분 간 초벌 증숙한 뒤, 고압가열 처리 0분(A), 10분(B), 20분(C), 40분(D) 실시하여 실험군의 품질특성 을 조사하였다. 그 결과 일반성분의 경우, 대체적으로 고 압가열 처리 유무에 따른 유의적 차이가 관찰되었으며, 고압가열 처리한 B, C, D 실험군의 수분함량, 조단백질, 조섬유가 고압가열 무처리군 A에 비해 감소하였고, 가용성 무질소물은 증가하는 것으로 나타났다. 가열 조건별 단호박 페이스트의 수용성식이섬유는 고압가열 20분 처리군인 C의 측정치가 2.02로 가장 높았으며 무처리군인 A의 1.60 보다 증가하였고, 고압가열 처리 40분의 경우 오히려 감소하는 것으로 나타났다. 색도의 L 값은 고압가열 무처리군인 A가 52.20에서 고압가열 처리 10분, 20분, 40분으로 시간이 증가함에 따라 각각 50.33, 49.46, 48.06으로 감소하였고, a 값과 b 값 또한 유의적인 차이를 보이며 감소하였다. 현미경을 통한 단호박 페이스트의 현탁액 입자를 관찰한 결과 카로티노이드를 포함하는 유세포가 관찰되었으며 고압가열 처리와 그 시간이 증가함에 따라 단호박 유세포의 변형이 뚜렷하게 관찰되었으나, 부유안정성 실험 결과 실험군 A, B, C, D 간 차이가 없었다. 이때, 가열조건의 선택은 수용성 식이섬유의 증가, 환원당 증가, 단맛의 관능특성이 유의적으로 높고, 전반적 기호도가 가장 우수한 것으로 나타난 고압가열 처리 20분인 C 실험군으로 결정하였다. 선택된 조건의 단호박 페이스트에 식품가공 시 널리 사용되는 검류인 xanthan gum, locust bean gum, guar gum을 단호박 페이스트에 종류별로 첨가하여 부유안정성을 확인하였는데, 이 결과 guar gum, locust bean gum, xanthan gum 순으로 부유안정성 효과를 나타냈으며 locust bean gum과 xanathan gum은 비슷한 정도의 효과를 보였다. 또한 관능검사를 통한 기호도 확인 결과 텍스쳐와, 전반적인 기호도가 가장 우수했으므로 locust bean gum(0.2%) 첨가 단호박 라떼의 품질이 가장 적절할 것으로 판단된다. For the production of pumpkin paste with respect to heating conditions, we steamed the pumpkin for roughly 15 min, heated it with high pressure treatment for 0 min (A), 10 min (B), 20 min (C), 40 min (D), and subsequently investigated the quality characteristics. Generally a significant difference was observed between the pumpkin paste treated with and without high-pressure heat. The values of water content, crude protein and crude fiber of the high-pressure heat-treated groups B, C, D were decreased compared with untreated group A. The soluble fiber in experimental group B sweet-pumpkin paste treated with high-pressure heat for 20 min was higher than the control, and the highest value at 2.02. Experimental group D sweet-pumpkin paste treated with high-pressure heat for 40 min was found to have a decreased soluble fiber content relative to the control. The L value for the color of the group A untreated control sweet-pumpkin paste (no high-pressure heating) decreased as the time increased from 10 min to 40 min, with L values of 50.33, 49.46, and 48.06, respectively. The b value for the color of the sweet-pumpkin paste also decreased, showing a significant difference. Taking into account all the results, we chose experimental group B in order to prepare sweet-pumpkin latte. We used 0.2% gum (xanthan gum, locust bean gum, guar gum) as a stabilizer. Sweet-pumpkin latte with xanthan and locust bean gum has a suspension stability effect that lasts 90 min. The L and b values of sweet-pumpkin latte with gums increase and a value decrease compared with the control. In terms of the overall acceptance of the sweet-pumpkin latte, the experimental group with xanthan gum scored the best.

지중내 공동 탐지를 위한 비파괴 검사 기법에 대한 실험적 연구

유정동(Jund Dong?Yoo),양학모(Hak Mo?Yang),장기창(Ki Chang?Jang),강승민(Seung Min?Kang),조소현(So Hyun?Cho),김현기(Hyun-Ki?Kim),Seung Soo?Kim,Da Bin?Jin 대한토목학회 2018 대한토목학회 학술대회 Vol.2018 No.10

가토에서 Vecuronium bromide 의 용량에 따른 근육이완 효과

김동원,이동호,민경호,전세웅,유희구,김경헌,승익상,김교상,서정국 대한마취과학회 1987 Korean Journal of Anesthesiology Vol.20 No.6

The introduction of muscle relaxants was an epoch making event in the development of clinical anesthesia and their use has hecame essential to anesthesia practice. Vecuronium, one of the newest muscle relaxants, many advantages; it is .apid acting, non-accumulating, has minimals side reactions and is promptly antagonized by anticholinesterases. However, its pharmacological effect, like other conventional muscle relaxants depends upon the dose and is influenced br many factors including body temperature, blood flow, interaction with other drugs, antibiotics, diuretics and so forth, To obtain a dose·response relationship which is important for clinical use, the effect of the vecuronium in various doses on the neuromuscular block in rabbits was investigated. The results were as follows. 1) In the vecuronium 0.025 mg/kg group, maximal twitch depression was varied between 75 to 92% with a mean value of 84,9%. The spontaneous recovery index was 141.0 seconds (2.35 min). 2) In the vecuranium 7.75 mg/kg group, thmean maximum twitch depression and spontaneous recovery index were 98.4% and 218.6 seconds (3.64 min.) respectively. 3) In the vecuronium 7.1 mg/kg group, maximum twitch depression was 100% and the spontaneous recovery index was markedly prolonged to 627.8 seconds (10.35 min).

Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats

Jeong, Dong Won,Kim, Young Hoon,Kim, Hui Hyun,Ji, Hye Young,Yoo, Sun Dong,Choi, Won Rack,Lee, Soo Min,Han, Chang-Kyun,Lee, Hye Suk WILEY PUBLISHERS 2007 BIOPHARMACEUTICS AND DRUG DISPOSITION Vol.28 No.2

<P>The pharmacokinetics of oleanolic acid was evaluated in vitro and in vivo. From Caco-2 cell permeation studies, oleanolic acid was a low permeability compound with no directional effects, suggesting a low in vivo absorption mediated by a passive diffusion. Oleanolic acid was metabolically unstable following incubation with rat liver microsomes in the presence of NADPH. After intravenous injection at doses of 0.5, 1 and 2 mg/kg doses, oleanolic acid showed dose-linear pharmacokinetics as evidenced by unaltered CL (28.6–33.0 ml/min/kg), V<SUB>ss</SUB> (437–583 ml/kg), dose-normalized AUC (16.0–17.9 µg min/ml based on 1 mg/kg) and t<SUB>1/2</SUB> (41.9–52.7 min). Following oral administration of oleanolic acid at doses of 10, 25 and 50 mg/kg, T<SUB>max</SUB>, t<SUB>1/2</SUB>, dose-normalized C<SUB>max</SUB> (66–74 ng/ml based on 25 mg/kg) and dose-normalized AUC (5.4–5.9 µg min/ml based on 25 mg/kg) were comparable between 25 and 50 mg/kg dose, but the plasma concentrations at 10 mg/kg dose were not measurable as they were below the limit of quantitation (2 ng/ml). The absolute oral bioavailability was 0.7% for oral doses of 25 and 50 mg/kg. The extent of urinary excretion was minimal for both i.v. and oral doses. The very low oral bioavailability of oleanolic acid could be due to a poor absorption and extensive metabolic clearance. Copyright © 2007 John Wiley & Sons, Ltd.</P>

대장직장 종양에 대한 내시경 점막하 절제술의 연대순 임상 결과와 학습 곡선

이상민 ( Sang Min Lee ),김은수 ( Eun Soo Kim ),박경식 ( Kyung Sik Park ),조광범 ( Kwang Bum Cho ),김동춘 ( Dong Choon Kim ),강유진 ( Yu Jin Kang ),이유진 ( Yoo Jin Lee ),이정민 ( Jung Min Lee ),최은성 ( Eun Sung Choi ),최재혁 ( Ja 대한소화기학회 2014 대한소화기학회지 Vol.64 No.4

Background/Aims: Endoscopic submucosal dissection (ESD) is an effective procedure for en-bloc curative resection of the colorectal tumor. As it requires high technical skills and experience in therapeutic endoscopy, it is important to understand learning curve of ESD technique. The aim of this study was to retrospectively describe the clinical results of ESD and to evaluate learning curve for the ESD of colorectal tumors. Methods: A total of 90 patients with 90 colorectal neoplasms, who had undergone ESD at a tertiary referral hospital from July 2009 to December 2012, were enrolled. The ESD was performed by a single endoscopist. All ESD cases were divided into three periods: first, cases 1-30; second, cases 31-60; and third, cases 61-90. Results: The en-bloc resection rates in third period (100%) was significantly higher than that of the first (93.3%) and second period (80%) (p=0.025). The perforation rate in third period (0%) also significantly decreased compared with that of the first (13.3%) and second period (20%) (p=0.032). To calibrate the difference of tumor size among periods, proficiency was calculated, as the procedure time per specimen area (min/cm2). The proficiency in third period (4.3) was significantly shorter than that of the first (16.8) and second period (10.2) (p=0.004). Conclusions: The learning curve of colorectal ESD in our study shows that at least 60 cases of ESD have to be conducted to acquire sufficient skill of degree without perforation. (Korean J Gastroenterol 2014;64:198-205)

조혈모세포이식 환자에서 침습성 진균 감염에 대한 이트라코나졸 액과 플루코나졸 시럽의 예방 효과 : 전향적, 무작위, 비교 임상시험

최수미,이동건,최정현,박선희,엄기성,김유진,김희제,민창기,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

목적 : 조혈모세포이식 환자에서 호중구 감소 기간 동안 이트라코나졸 액(ITZS)과 플루코나졸 시럽(FCZS)의 진균 감염에 대한 예방 효과를 전향적으로 비교해 보고자 하였다. 재료 및 방법 : 2001년 8월부터 2002년 6월까지 가톨릭 조혈모세포이식센터에 입원하여 동종 조혈모세포이식을 받은 만 18세 이상의 환자들을 각각 ITZS와 FCZS군으로 무작위 배정하여 침습성 진균 감염 발생과 약제 관련 부작용을 전향적으로 조사하였다. 결과 : ITZS군에 40명, FCZS군에 38명이 배정되었고, FCZS군 환자의 평균 나이가 더 많았다. 시험 약제 평균투여기간은 ITZS군 16.4일, FCZS군 21.9일로 ITZS군이 더 짧았다. 이는 ITZS군에서 소화기 부작용으로 인한 약제 중단이 더 많았기 때문으로 보인다. 시험 약제 투여 후 총 빌리루빈 수치의 유의한 증가가 관찰되었으나, 약제 관련 부작용은 모든 환자에서 가역적이었다. 호중구감소 기간동안 표재성 진균 감염은 두 군에서 모두 발생하지 않았고, 침습성 진균 감염은 ITZS군 5명(12.5%), FCZS군 8명(21.1%)으로 FCZS군에서 많았으나, 통계학적으로 유의하지 않았고, 사망률에도 유의한 차이는 없었다. 결론 : 침습성 진균 감염에 대한 이트라코나졸 액과플루코라졸 시럽의 예방 효과에 유의한 차이는 없었으나, 앞으로 더 많은 환자를 대상으로 잘 짝지어진 대조군 연구가 필요할 것으로 보인다. 부작용 중 간독성과 관련하여 이식시 투여되는 여러 약제들과의 상호작용에 대한 연구도 필요할 것이다. Background : Though fluconazole is widely used for antifungal prophylaxis, it is ineffective against mould infections including Aspergillus species. Itraconazole has a broader spectrum than fluconazole but the capsule form shows erratic bioavailability in neutropenic patients. In this study, we compared itraconazole oral solution (ITZS) with fluconazole syrup (FCZS) for the prevention of invasive fungal infection (IFI) in allogeneic hematopoietic stem cell transplant recipients. Materials and Methods : Adults receiving allogeneic hematopoietic stem cell transplantation (HSCT) from september 2001 to June 2002, were randomly allocated to either the ITZS group or the FCZS group. We prospectively evaluated the safety and efficacy of each drug. Results : Out of 78 patients (40 patients in the ITZS group and 38 patients in the FCZS group) who were eligible for this study, 37 patients completed the course of prophylaxis without any evidence of IFI. The mean duration of prophylaxis was 16.4 days for the ITZS group and 21.9 days for the FCZS group (P<0.006). Drug-related adverse events occurred in 28 patients (70.0%) and 19 patients (50.0%) in the ITZS group and the FCZS group, respectively. Common adverse events of ITZS were nausea, vomiting, and diarrhea. Drug-related reversible hepatotoxicity occurred in 4 patients in the ITZS group. There was a significant elevation of total bilirubin level in the ITZS group. The incidence of suspected IFI occurred in 5 patients (12.5%) who received ITZS, compared with 8 (21.1%) who received FCZS (P=0.372). There were no proven IFIs or superficial (oral/vaginal) fungal infections in both groups. Overall mortality was not different between the two groups (2.5% in the ITZS group versus 5.3% in the FCZS group, P=0.610). Conclusion : ITZS and FCZS showed similar protection against IFI during pre-engraftment period. Poor tolerability due to gastrointestinal troubles of ITZS might limit its success as prophylactic therapy. Well matched controlled study with large number of patients will be required in the future.

D-Amphetamine이 니코틴성 흥분작용에 의한 카테콜아민 분비작용에 미치는 영향

임건한,서유석,민선영,임지연,김용직,나광문,임동윤 朝鮮大學校 附設 醫學硏究所 2005 The Medical Journal of Chosun University Vol.30 No.1

본 연구의 목적은 d-arphetamine이 흰쥐의 적출부신 관류모델에서 니코틴 수용체 흥분에 의한 카테콜아민(CA) 유리작용에 미치는 영향을 검색하여 그 작용기전을 규명하고자 하였다. D-amphetamine은 흰쥐 부신정맥내로 60분간 관류시 d-amphetamine자체는 약한 CA 분비작용을 나타내었으나, d-amphetamine (30 μM)을 비롯한 강력한 neuronal nicotine 수용체 작용제인 cytisine (50 μM) 및 epibatidine (30 μM)에 의한 CA 유리작용을 처음 4-10분 동안만 유의하게 증강시켰다. 또한, d-amphetamine (30 μM)은 60분간 부신정맥 내로 관류한 상태에서 dihydropyridine L-형 칼슘통로 개방약물인 Bay-K-8644 (10 μM)과 세포질내 칼슘저장고에서 Ca^(2+) ATPase 억제제인 cyclopiazonic acid (10 μM)의 CA 유리작용을 처음 4분간만 유의하게 증강시켰다. 그러나, 고농도의 d-amphetamine (500 μM)은 상기한 모든 분비촉진제의 CA분비작용을 오히려 억제하였다. 이와 같은 연구결과로 보면, 흰쥐 관류 부신수질에서 d-amphetamine은 낮은 농도에서는 콜린성 니코틴 수용체 흥분에 의한 카테콜아민 분비반응을 증강시키지만, 고농도에서는 오히려 억제적으로 작용함을 시사한다. 따라서, d-amphetamine은 용량에 따라서 흰쥐 적출 관류부신수질의 니코틴 수용체의 작용제 및 길항제로 이중 작용(dual action)을 나타내는 것으로 생각된다. 이러한 d-amphetamine의 작용은 흰쥐 부신수질 크롬친화세포의 dihydropyridine계 L-형 칼슘통로의 활성화 및 세포 내 칼슘저장고로부터 칼슘유리작용과 관련성이 있는 것으로 사료된다. The purpose of the present study was to examine the effect of d-amphetamine on CA release evoked by nocotinic receptor stimulation from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. D-amphetamine(30 μM), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced the CA secretory responses evoked by ACh (5.32 mM), nicotine (30 μM), cytisine (50 μM, a selective neuronal nicotinic Nn-receptor agonist) and epibatidine (30 nM, a selective neuronal nicotinic Nn receptor agonist) only for the first period (4~10 min), although it alone has weak effect on CA secretion. Moreover, d-amphetamine (30 μM) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type Ca^(2+) channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca^(2+) ATPase only for the first peroid (4 min). However, in the presence rather inhibited the CA secretory responses evoked by the above all of secretagogues. Taken together, these experimental results suggest that d-amphetamine at a low concentration enhances the CA secretion from the rat adrenal medulla evoked by stimulation of cholinergic nicotininc receptors, but at a high concentration it rather inhibits them. It semms that d-amphetamine has dual action acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which are might be dependent on the concentration. It is also thought that these actions of d-amphetamine are probably relevant to the activation of the dihydropyridine L-type Ca^(2+) channels located on the rat adrenomedullary chromaffin cell membrane and release of Ca^(2+) from the cytoplasmic store.

조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,이동건,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic, 24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12 days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting, diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large, prospective, and randomized comparative studies are warranted for aspergillosis.