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).

Development of Simultaneous Analytical Method for ImidazolinoneHerbicides from Livestock using LC-MSMS

Hyo-Min Heo,Hyeong-WookJo,Kyu-Won Hwang,Jung-Hun Sun,Joon-Kwan Moon 한국농약과학회 2021 한국농약과학회 학술발표대회 논문집 Vol.2021 No.11

Simultaneous analytical method using LC/MSMS for imidazolinone herbicides from livestock (egg, milk, beef, pork and chicken) for monitoring was developed with QuEChERS preparation. Sample weighing (5g) in a 50mL conical tube, added 0.1 M potassium phosphate dibasic solution (5mL) was shaken for 10min. After 0.5mL 6 NHCl, 10mL acetonitrile were added, it was shaken for 10min. And QuEChERS extraction salt (Original method, 4g MgSO₄, 1g NaCl) were added to the sample in the 50 mL conical tube. The mixture was strongly shaken for 1 min and was centrifuged at 3,000g for 10 min. The acetonitrile layer was purification with dSPE (150mg MgSO₄, 25mg C18) and was centrifuged at 13,000g for 5min. The supernatant was filtered with a membrane filters (pore size: 0.2um) before analysis. ME (%, Matrix effect) for almost analytes range were -6.56 to 5.70%. MLOD (Method LOD) and MLOQ (Method LOQ) was calculated by S/N ratio. MLOQs were 0.01 mg/kg. The linear correlation coefficients (r2) were > 0.99 within the range of 2 ~ 100 ug/kg for all of the 3 imidazolinone herbicides. The percentages (of imidazolinone herbicides) recovers were in the range of 84.1 ~ 110.6% (0.01mg/kg level), 90.8 ~ 97.1% (0.1mg/kg level) and 94.4 ~ 102.1% (0.5mg/kg level) within the validation criteria (recover; 70-120% with RSD < 20%)

Comparative evaluation of the algorithms for parametric mapping of the novel myocardial PET imaging agent ¹⁸ F-FPTP

Kim, Ji Who,Seo, Seongho,Kim, Hyeon Sik,Kim, Dong-Yeon,Lee, Ho-Young,Kang, Keon Wook,Lee, Dong Soo,Bom, Hee-Seung,Min, Jung-Joon,Lee, Jae Sung Springer Japan 2017 Annals of nuclear medicine Vol.31 No.6

<P><B>Objective</B></P><P>(<SUP>18</SUP>F-fluoropentyl)triphenylphosphonium salt (<SUP>18</SUP>F-FPTP) is a new promising myocardial PET imaging tracer. It shows high accumulation in cardiomyocytes and rapid clearance from liver. We performed compartmental analysis of <SUP>18</SUP>F-FPTP PET images in rat and evaluated two linear analyses: linear least-squares (LLS) and a basis function method (BFM) for generating parametric images. The minimum dynamic scan duration for kinetic analysis was also investigated and computer simulation undertaken.</P><P><B>Methods</B></P><P><SUP>18</SUP>F-FPTP dynamic PET (18 min) and CT images were acquired from rats with myocardial infarction (MI) (<I>n</I> = 12). Regions of interest (ROIs) were on the left ventricle, normal myocardium, and MI region. Two-compartment (<I>K</I><SUB>1</SUB> and <I>k</I><SUB>2</SUB>; 2C2P) and three-compartment (<I>K</I><SUB>1</SUB>–<I>k</I><SUB>3</SUB>; 3C3P) models with irreversible uptake were compared for goodness-of-fit. Partial volume and spillover correction terms (<I>V</I><SUB><I>a</I></SUB> and <I>α</I> = 1 − <I>V</I><SUB><I>a</I></SUB>) were also incorporated. LLS and BFM were applied to ROI- and voxel-based kinetic parameter estimations. Results were compared with the standard ROI-based nonlinear least-squares (NLS) results of the corresponding compartment model. A simulation explored statistical properties of the estimation methods.</P><P><B>Results</B></P><P>The 2C2P model was most suitable for describing <SUP>18</SUP>F-FPTP kinetics. Average <I>K</I><SUB>1</SUB>, <I>k</I><SUB>2</SUB>, and <I>V</I><SUB><I>a</I></SUB> values were, respectively, 6.8 (ml/min/g), 1.1 (min<SUP>−1</SUP>), and 0.44 in normal myocardium and 1.4 (ml/min/g), 1.1 (min<SUP>−1</SUP>), and 0.32, in MI tissue. Ten minutes of data was sufficient for the estimation. LLS and BFM estimations correlated well with NLS values for the ROI level (<I>K</I><SUB>1</SUB>: <I>y</I> = 1.06<I>x</I> + 0.13, <I>r</I><SUP><I>2</I></SUP> = 0.96 and <I>y</I> = 1.13<I>x</I> + 0.08, <I>r</I><SUP><I>2</I></SUP> = 0.97) and voxel level (<I>K</I><SUB>1</SUB>: <I>y</I> = 1.22<I>x</I> − 0.30, <I>r</I><SUP><I>2</I></SUP> = 0.90 and <I>y</I> = 1.26<I>x</I> + 0.00, <I>r</I><SUP><I>2</I></SUP> = 0.92). Regional distribution of kinetic parametric images (<I>αK</I><SUB>1</SUB>, <I>K</I><SUB>1</SUB>, <I>k</I><SUB>2</SUB>, <I>V</I><SUB>a</SUB>) was physiologically relevant. LLS and BFM showed more robust characteristics than NLS in the simulation.</P><P><B>Conclusions</B></P><P>Fast kinetics and highly specific uptake of <SUP>18</SUP>F-FPTP by myocardium enabled quantitative analysis with the 2C2P model using only the initial 10 min of data. LLS and BFM were feasible for estimating voxel-wise parameters. These two methods will be useful for quantitative evaluation of <SUP>18</SUP>F-FPTP distribution in myocardium and in further studies with different conditions, disease models, and species.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s12149-017-1171-6) contains supplementary material, which is available to authorized users.</P>

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

위암 환자의 복강내 투여를 위한 Activated Charcoal-Alginate Bead 제형으로부터 Mitomycin C의 용출 거동

이진호,최선웅,서중기,김동민,정경수,오정연,김진향,노승무,민병무,김용백,김창식,박근성,강대영,송규상,양준묵,조준식,정현용,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

Locoregional recurrence is the most common type of recurrence in surgical operation of gastric adenocarcinoma, and peritoneal dissemination is one of the most difficult problems in advanced gastric adenocarcinoma treatment. Because the peritoneal cavity is the most common site of the first recurrence after gastric cancer resection, intraperitoneal chemotherapy seems a logical choice for cancer chemotherapy. In this study, Mitomycin C (MMC)-activated charcoal (CH)-alginate (ALG) beads were prepared by the mixtures of CH particles adsorbed with MMC as an anti-cancer drug and aqueous alginate solution. The alginate is recognized as biodegradable, nontoxic, and biocompatible. The release of MMC from the beads in 0.1 M Tris buffer was stable and continuous until about 1 week. The MMC-CH-ALG beads can be applied in the peritoneal cavity for intraperitoneal chemotherapy since they provide a good adhesiveness on the tissue and controlled release pattern of the drugs.

크론병에 대한 CoPPLX의 방어효과에 대한 연구

이호학,김유림,문창기,이재일,양병윤,김종수,이정민,정재혁,안석진,박상준,김윤권,김소연,김영중,조민구,최영자,장성조 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

핵의학적 리포터 유전자 영상

민정준 대한핵의학회 2004 핵의학 분자영상 Vol.38 No.2

Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studies published to date demonstrate that reporter gene imaging technologies will help to accelerate pre-clinical model validation as well as allow for clinical monitoring of human diseases. (Korean J Nucl Med 38(2):143-151, 2004)

신혈관근지방종 파열에 의한 신성복증 1례

민영기,정윤석,박인철,조준필 대한응급의학회 2000 대한응급의학회지 Vol.11 No.3

The case of a patient with acute onset of flank pain is presented. Initial therapy was directed toward relief of pain believed to be caused by renal calculi. The flank pain did not responded to analgesics. An abdominal ultrasonogram showed that multiple hyperechogenic masses were in the parenchyma of both kidney, and an abdominal CT showed that multiple high-density masses, presumed to be angiomyolipomas, were located in both kidneys and in the perirenal hematoma around the left kidney. Vital signs were stable, and there was no evidence of anemia. On the seventh hospital day, angiographic tumor embolization was performed. Cases such as this should remind emergency physicians to carefully consider alternate diagnoses to renal calculi in patients with flank pain who have atypical clinical features or an atypical course.

신성고혈압 흰쥐에서 측뇌실내 Captopril이 Bradykinin의 중추승압효과에 미치는 영향

정태호,양민준,오승호,전제열,염철호,윤평진 조선대학교 1994 The Medical Journal of Chosun University Vol.19 No.2

Effects of intracerebroventricular captopril on the central pressor response to bradykinin were examined in normotensive and 2-kidney, 1 clip (2KIC) Goldblatt hypertensive rats. The experiment was done under pentobarbital (50 ㎎/㎏. IP) anesthesia. Captopril (1 ㎎)and bradykinin (5 nmol) were administered into the right lateral cerebral ventricle, while arterial blood perssure and heart rate were continuously monitored throughout the experiment. Intracerebroventricular captopril did not affect the blood pressure within 10 minutes in both normotensive and 2KIC hypertensive rats, while it significantly augmented the central pressor response to bradykinin in the hypertensive rats. These observations suggest that an elevation in endogenous kinin levels is without effect on arterial pressure in normotensive and 2KIC hypertensive rats. However, the kallikreinkinin system in the central nervous system plays a role in the regulation of blood pressure, possibly maintaining the hypertension, in 2KIC hypertensive rats.

한국 성인에서의 후두개염의 방사선학적 진단기준

민영기,정윤석,윤상규,박인철,조준필 대한응급의학회 2000 대한응급의학회지 Vol.11 No.3

Backgrounds: A retrospective study was performed to define objective radiologic parameters in diagnosing epiglottitis on soft-tissue lateral neck radiographic study. Methods: Parameters of soft-tissue structures(epiglottis width, third vertebral body width, ratio of epiglottic width to third vertebral body width) in 30 adult patients compared with those of age and sexmatched controls with foreign body in throat whose radiographic reading was normal. Results: Epiglottis width of more than 11mm, ratio of epiglottis width(EW) to the third vertebral body width(C3W) of more than 0.5 were, respectively, found to be 100% sensitive and specific in differentiating between patients with and without epiglottitis. Conclusion: These preliminary results suggest that EW/C3W ratio of more than 0.5, EW of more than 11mm, respectively, may be useful in the diagnosis of epiglottitis in adult patients.