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).

Genomewide Expression Profile of Forsythia Suspensa on Lipopolysaccaride-induced Activation in Microglial Cells

Sohn, Sung-Hwa,Ko, Eun-Jung,Kim, Yang-Seok,Shin, Min-Kyu,Hong, Moo-Chang,Bae, Hyun-Su The Korean Society of Toxicogenomics and Toxicopro 2008 Molecular & cellular toxicology Vol.4 No.2

Microglia, which is the primary immune effector cells in the central nervous system, constitutes the first line of defense against infection and injury in the brain. The goal of this study was to determine the protective (anti-inflammation) mechanisms of forsythia suspense (FS) on LPS-induced activation of BV-2 microglial cells. The effects of FS on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100mm dish $(1{\times}10^7/dish)$ for 24hr and then pretreated with $1{\mu}g/mL$ FS or left untreated for 30 min. Next, $1{\mu}g/mL$ LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min, 1hr, and 3hr. The gene expression profiles of the BV-2 microglial cells varied depending on the FS. The oligonucleotide microarray analysis revealed that MAPK pathway-related genes such as Mitogen activated protein kinase 1 (Mapk1), RAS protein activator like 2 (Rasal2), and G-protein coupled receptor 12 (Gpr12) and nitric oxide biosynthesis-related genes such as nitric oxide synthase 1 (neuronal) adaptor protein (Nos1ap), and dimethylarginine dimethylaminohydrolase 1 (Ddah1) were down regulated in FS-treated BV-2 microglial cells. FS can affect the MAPK pathway and nitric oxide biosynthesis in BV-2 microglial cells.

Dry etching of polydimethylsiloxane using microwave plasma

Hwang, Sung Jin,Oh, Dong Joon,Jung, Phill Gu,Lee, Sang Min,Go, Jeung Sang,Kim, Joon-Ho,Hwang, Kyu-Youn,Ko, Jong Soo IOP 2009 JOURNAL OF MICROMECHANICS AND MICROENGINEERING - Vol.19 No.9

<P>This paper presents a new polydimethylsiloxane (PDMS) dry-etching method that uses microwave plasma. The applicability of the method for fabricating microstructures and removing residual PDMS is also verified. The etch rate of PDMS was dominantly influenced by the gas flux ratio of CF<SUB>4</SUB>/O<SUB>2</SUB> and the microwave power. While the PDMS etch rate increased as the flux ratio of CF<SUB>4</SUB> was increased, the etch rate decreased as the flux ratio of O<SUB>2</SUB> was increased. The maximum etch rate of 4.31 µm min<SUP>−1</SUP> was achieved when mixing oxygen (O<SUB>2</SUB>) and tetrafluoromethane (CF<SUB>4</SUB>) at a 1:2 ratio at 800 W power. The PDMS etch rate almost linearly increased with the microwave power. The ratio of the vertical etch rate to the lateral etch rate was in a range of 1.14–1.64 and varied with the gas fluxes. In consideration of potential applications of the proposed PDMS etching method, array-type PDMS microwells and network-type microprotrusion structures were fabricated. The contact angle was dramatically increased from 104° (non-etched PDMS surface) to 148° (etched PDMS surface) and the surface was thereby modified to be superhydrophobic. In addition, a thin PDMS skin that blocked holes and PDMS residues affixed in nickel microstructures was successively removed.</P>

Genome Wide Expression Profile of Asiasarum sieboldi in LPS-stimulated BV-2 Microglial Cells

Sohn, Sung-Hwa,Ko, Eun-Jung,Kim, Yang-Seok,Shin, Min-Kyu,Hong, Moo-Chang,Bae, Hyun-Su The Korean Society of Toxicogenomics and Toxicopro 2008 Molecular & cellular toxicology Vol.4 No.3

Recent studies suggest that activated microglial cells play an essential role in the inflammatory responses and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. This study was conducted to evaluate the protective mechanisms of Asiasarum sieboldi (AS) on LPS-induced activation of BV-2 microglial cells. The effects of AS on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100 mm dish ($1{\times}10^7$/mL) for 24 h and then pretreated with 1 ${\mu}g$/mL AS or left untreated for 30 min. Next, 1 ${\mu}g$/mL LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min and 1 hr. The gene expression profiles of the BV-2 microglial cells varied depending on the AS. The microarray analysis revealed that MAPK signaling pathway-related genes were downregulated in AS-treated BV-2 microglial cells. AS can affect the neuroinflammatory-related pathway such as MAPK signaling pathway in activated BV-2 microglial cells.

개의 췌도분리에서 췌장의 팽창과 콜라겐 분해요소

이상훈,김성주,박정환,김종성,오승훈,한진수,정인경,양태영,김동준,김광원,이문규,민용기,이명식,정재훈,함종렬 대한당뇨병학회 2000 Diabetes and Metabolism Journal Vol.24 No.2

Backgrounds: One of the main problems conditioning the outcome of islet transplantation is the ability to separate a sufficient number of viable islets with preserved function. Islet purification is critically affected by all of the isolation stages. Thus, it is necessary to set up the standard isolation method that islets are separate well from acinar without compromising islet yield and viability. Methods: Twenty three adult mongrel dogs were used for the experiment of total pancreatectomy with islet isolation. The islets were properly isolated by a modified Recordi method. The obtained islets were further purified by centrifugation on discontinuous gradients using cell separation system (Model 2991, Cobe, Lakewood Colo). We evaluated islet number (islet equivalent number, 150 um equivalents/kg of recipient body weight, IEq/kg), purity, cell volume, viabilty, recovery rate, and comparison of outcome according to the isolation conditions. Results: 1) The mean of islet numbers before purification were 13543±9431Eq/kg, digestion times were 13.8±2.6 min., digestion temperature was 37.4±0.2℃, purity was 59.7?.0%, viability was 90.0±2.1%, cell volume was 4.7±1.1 mL, islet number after purification were 4064±361 IEq/kg, and recovery rate was 29±2.9%. 2) Isolated islet numbers were different according to the degree of pancreas distension with collagenase, digestion temperature, and digestion time. 3) The best conditions for islet isolation were above 37.5℃ in temperature at recirculation of collagenase, within 12 min in digestion time and well distended pancreas with collagenase. 4) According to multiple regression adjusted by variable factors, the degree of pancreas distension with collagenase and digestion time were independently associated factors for successful islet isolation. Conclusions: In this study, we concluded that the degree of pancreas distension with collagenase and digestion time were independent factors for successful islet isolation and the best conditions for islet isolation were above 37.5℃ in temperature at recirculation of collagenase, within 12 min in digestion time and well distended pancreas with collagenase.

Genome Wide Expression Profile of Agrimonia pilosa in LPS-stimulated BV-2 Microglial Cells

Sohn, Sung-Hwa,Ko, Eun-Jung,Kim, Sung-Hoon,Kim, Yang-Seok,Shin, Min-Kyu,Hong, Moo-Chang,Bae, Hyun-Su The Korean Society of Toxicogenomics and Toxicopro 2009 Molecular & cellular toxicology Vol.5 No.1

Microglial cells constitute the first line of defense against infection and injury in the brain. This study was conducted to evaluate the protective mechanisms of Agrimonia pilosa (AP) on LPS-induced activation of BV-2 microglial cells. The effects of AP on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100 mm dish ($1{\times}10^7/mL$) for 24 hr and then pretreated with 1 g/mL AP or left untreated for 30 min. Next, 1 g/mL LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min, 3 hr and 6 hr. The gene expression profiles of the BV-2 microglial cells varied depending on the AP. The microarray analysis revealed that MAPK signaling pathway-related genes were down-regulated and IL10 gene was up-regulated in AP-treated BV-2 microglial cells. AP can affect the inflammatory response and MAPK pathway in BV-2 microglial cells.

습식텍스쳐를 이용한 단결정 실리콘 광학적 · 전기적 특성 연구

한규민(Han Kyu-min),유진수(Yoo Jin-su),유권종(Yoo Kwon-jong),이희덕(Lee Hi-deok),최성진(Choi Sung-jin),권준영(Kwon Jun-young),이준신(Yi Jun-sin) 한국태양에너지학회 2010 한국태양에너지학회 학술대회논문집 Vol.2010 No.4

The presence of ultrasonic wave in caustic cleaning process enhances the remove pollutants, and more homogeneous, textured structure. The silicon wafers, cleaning in Deconex OF 145 solution (0.5~2wt %) with DIW under ultrasonic environment for 5 min. The presence of uniform thin layer of SiO2 on c-Si surface enhances etching rate in the caustic etching mixture solution of NaOH (1.5 wt %), DI water and IPA (6 wt %) at 90℃ for 20 min and results in a fine, more homogeneous and small textured structure.

An Investigation of the Stability of Y₂O₃ and Sintering Behavior of Fe-Based ODS Particles Prepared by High Energy Ball Milling

Park, Eun-Kwang,Hong, Sung-Mo,Park, Jin-Ju,Lee, Min-Ku,Rhee, Chang-Kyu,Seol, Kyeong-Won The Korean Powder Metallurgy Institute 2013 한국분말재료학회지 (KPMI) Vol.20 No.4

Fe-based oxide dispersion strengthened (ODS) powders were produced by high energy ball milling, followed by spark plasma sintering (SPS) for consolidation. The mixed powders of 84Fe-14Cr-$2Y_2O_3$ (wt%) were mechanically milled for 10 and 90 mins, and then consolidated at different temperatures ($900{\sim}1100^{\circ}C$). Mechanically-Alloyed (MAed) particles were examined by means of cross-sectional images using scanning electron microscopy (SEM). Both mechanical alloying and sintering behavior was investigated by X-ray diffraction (XRD) and high resolution transmission electron microscopy (HR-TEM). To confirm the thermal behavior of $Y_2O_3$, a replica method was applied after the SPS process. From the SEM observation, MAed powders milled for 10 min showed a lamella structure consisting of rich regions of Fe and Cr, while both regions were fully alloyed after 90 min. The results of sintering behavior clearly indicate that as the SPS temperature increased, micro-sized defects decreased and the density of consolidated ODS alloys increased. TEM images revealed that precipitates smaller than 50 nm consisted of $YCrO_3$.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

원인 불명의 실신 환자의 진단에 있어서 Head - up tilt Test 의 유용성과 혈관미주신경성 실신 환자의 임상적 특징

윤호중(Ho Joong Youn),정욱성(Wook Sung Chung),백상홍(Sang Hong Baek),김철민(Chul Min Kim),박인수(In Soo Park),김재형(Jae Hyung Kim),최규보(Kyu Bo Choi),홍순조(Soon Jo Hong) 대한내과학회 1994 대한내과학회지 Vol.47 No.2

N/A Background: Syncope, defined as a transient loss of consciousness, is a frequently encountered symptom, but despite thorough clinical and invasive diagnostic investigation, the cause of syncope remains unexplained. In recent years, head-up tilt test has been of increasing interest as a diagnostic aids in patients with unexplained syncope. We studied to define the usefulness of various diagnostic test in the evaluation of patients with recurrent syncope, to assess the usefulness of head-up tilt test in the working of syncope of unknown origin and to evaluate the clinical characteristics of subgroups of patients with syncope induced by head-up tilt test. Methods: Between June, 1991 and November, 1992 at St. Mary`s hospital, 21 patients with history of syncope and 24 control subjects without history of syncope underwent 60° head-up tild test for 60 min. Results: 1) The definite cause for recurrent syncope were diagnosed in 10 of patients (47,6%) after clinical and invasive tests. 2) During head-up tilt test, vasovagal responses were provoked in 5 of 21 patients (23.8%) with recurrent syncope and 1 of 24 patients (4.2%) without syncope (p<0,05). 3) The head-up tilt test induced symptomatic bradycardia or hypotension in 3 of 10 patients (30%.) with negative electrophysiologic results. 4) During tilt induced vasovagal response, a) mean heart rate decreased to 42±24 beat/min from supine control of 70±12 beat/min (p<0. 05), b) mean systolic blood pressure decreased to 95±12 mmHg from supine control of 120±S mmHg (p<0,05), c) mean diastolic blood pressure decreased to 60±21mmHg from supine control of 72±13 mmHg (p<0.05), d) the time interval to onset of vasovagal response was 22±12 min. Conclusions: 1) In a large proportion of patients with recurrent syncope, the diagnosis remains unexplained despite a neurologic and cardiologic investigation including an electrophysiologic study. 2) Vasovagal responses are frequent cause in patients with recurrent unexplained syncope. 3) The head-up tilt test may be a simple, safe and highly yielding provocative test in the investigation of syncope of unknown origin.