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).

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.

捻轉法이 竝行된 鍼刺戟 및 電鍼刺戟이 鎭痛效果에 미치는 影響

金志勳,盧植,閔炳一,朴東錫 경희대학교 1998 慶熙醫學 Vol.14 No.3-4

성인 지역사회 폐렴의 원인 미생물에 대한 전향적 다기관 연구 : Legionella, Leptospira, Hantaan virus and Orientia tsutsugamushi

김민자,정희진,손장욱,심희선,박대원,박승철,우준희,강재명,김유겸,신완식,김양리,이환종,김지희 대한감염학회 2001 감염 Vol.33 No.1

Background : Despite rigorous investigations, the etiology of community-acquired pneumonia remains unknown in about 50% of hospitalized patients. The diagnosis of the etiological agent is becoming more challenging and more critical as number of newer pathogens have been recognized in recent years. In the 3-year period prospective study we investigated adult patients with community-acquired pneumonia for Legionella, Leptospira, Hantaan virus and Orientia tsutsugamushi as potential etiologic agents. Methods : A prospective multicenter study was performed from May 1997 to April 2000. A total of 431 patients with community-acquired pneumonia under the inclusion criteria were examined for specific microbial diagnosis; sputum culture and PCR, and serologic teats including indirect immunofluorescence antibody (IFA) test for Legionella, and hemagglutination tests for Leptosoira, Hantaan virus and O. tsutsugamushi. Etiologic diagnosis was determined on the basis of the review of case record forms and specific laboratory diagnostic criteria. Results : During the study period a total of 385 sputum and 283 serum samples were examined. Legionella pneumonia was diagnosed in 2.3% (10/431) of the cases examined : 1.4% cases with PCR-positive (5/367) and 2.1% with positive IFA test (6/283). Leptospirosis and scrub typhus were diagnosed in 0.4% (1/252) and 2.0% (5/252), respectively. All 5 cases with scrub typhus occurred in late fall, and rash or eschar was not found. None of cases was Hantaan virus infection. Conclusion : The results suggest that Legionella, Leptospira, and O. tsutsugamushi should be considered in the etiologic diagnosis and empirical antibiotic therapy of community-acquired pneumonia. (Korean J Infect Dis 32:24∼31, 2001)

염전법이 병행된 침자극 및 전침자극이 진통효과에 미치는 영향

朴東錫,閔炳一,盧植,金志勳 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 1998 東西醫學硏究所 論文集 Vol.1998 No.-

Twirling the needle (TN) is one of several needling methods frequently used for acupuncture in the oriental medicine. The present study was conducted to see if TN enhanced the antinociceptive effect produced by plainor electroacupuncture in the rat tail flick test. Rats (Sprague-Dawley, 200~300g) lightly anesthetized with thiopental sodium (40mg/kg, i.p.) were used in the tail-flick test. The basal reaction time for tail-flick was 2 sec. For "plain" acupuncture (PA), a needle was inserted for 20 min into a Chock-samni(ST36) acupuncture point which (is located at the anterior tibial muscle and about 10mm below the knee joint). For electroacupuncture (EA), train-pulses (3Hz, 0.3ms pulse width, 0.2!0.3mA) were applied to the inserted needle for the period of insertion. For combining TN with either PA or EA, TN was performed during the each acupuncture period. Two methods for TN were used; twirling 3 times for 1 second persisted for 1 min in every 5 mins (long-duration and long-interval; LDLI)and twirling 3 times for 1 second persisted for 10 sec in every 1 min (short-duration and short-interval; SDSI). PA and EA produced an increase in tail flick latency (TFL); peak increases were 21.3??5.1% and 42.1??17.3% of the pre-acupunture control, respectively, and occurred immediately after cessation of 20 min-acupuncture. Performing TN combined with PA increased TFL more than PA itself by showing a greater peak increase in TFL when performed with a SDSI-TN than with a LDLI-TN (60.6??12.5% and 42.7??22.7% of the pre-acupuncture control, respectively). Performing TN combined with EA also increased TFL more than EA itself and a greater peak increase in TFL was observed with a SDSI-TN as compared to a LDLI-TN (77.5??13.8% and 67.3??14.0% of the pre-acupuncture control, respectively). These results indicate that TN enhances both PA-and EA-produced antinociception where an enhanced antinociception than a LDLI-TN. It is suggested that performing a SDSI-TN combined with EA seems to be one of the most effective ways to produce analgesia.

Protective Effects of N-acetylcystenine and Selenium against Doxorubicin Toxicity in Rats

Yeo-sung Yoon,Sun-don Kim,Min-hye Lee,Heung-shik S.Lee,In-se Lee,Je-kyung Sung,Eun-sung Park 대한수의학회 2003 Journal of Veterinary Science Vol.4 No.2

Effects of N-acetylcysteine and Selenium against Doxorubicin Toxicity in RatsEun-sung Park, Sun-don Kim1, Min-hye Lee, Heung-shik S. Lee, In-se Lee, Je-kyung Sung and Yeo-sung Yoon*

Flavobacterium meningosepticum에 의한 균혈증 1예

장성원,유진홍,진승원,김선우,김연식,박순민,이대훈,최민호,최주연,신완식,강문원,강지민 대한화학요법학회 1997 대한화학요법학회지 Vol.15 No.1

1996년 6월 카톨릭대학교 부천성가병원에 뇌경색으로 입원했던 61세 남자 환자의 혈액에서 Flavobacterium meningosepticum을 분리하였다. 환자는 폐렴을 동반한 패혈증의 예로 ceftriaxone과 metronidazole을 투여하였으나 입원 48시간만에 사망하였다. Flabovacterium meningosepticum is a rae cause of nosocomial infection which shows multi-drug resistance. It mainly invades patients with impaired immunity. Recently, we experienced a case of F. meningosepticum bacteremia in a patient with chronic debilitated state owing to stroke. The clinical progress was so rapid that he died within 48 hours. Blood culture revealed F. meningosepticum which showed characteristic yellow colony in blood agar plate.

다량의 하부위장관출혈이 병발된 Vibrio vulnificus 패혈증 1예

최주연,유진홍,한석원,이대훈,최민호,박순민,김연식,김선우,신완식,강문원,강성구 대한화학요법학회 1996 대한화학요법학회지 Vol.14 No.2

최근 저자들은 Vibrio vulnificus 감염에 의해 패혈증 및 이차성 피부 병변을 보인 42세의 남자 환자의 치료중 하부 위장관 출혈이 병발된 1예를 경험하였기에 보고하는 바이다. We experienced a case of Vibrop vulnificus septicemia which showed an unusual manifestation such as hematochezia. The patient was a 42-year-old man with chronic liver disease. The blood and wound culture revealed the organism. During intensive care, he suffered from massive hematochezi for several days. Colonoscopy and abdominal CT showed findings suspicious of ischemic colitis. To our knowledge, this is the first unusual case of V.vulnificus infection which showed massive lower gastrointestinal bleeding.

하수오와 백수오가 난소적출로 유발된 흰쥐의 골다공증 예방효과에 미치는 영향

김민정,서부일,신순식,박지하 대한본초학회 2004 大韓本草學會誌 Vol.19 No.1

Objectives : The present study has been undertaken to investigate the effects of Polygoni Multiflori Radix and Cynanchi Wilfordii Radix on prevention of osteoporosis in ovariectomized rats. Methods : In this experiment, the rats were ovariectomized. Rats were administered by 2 kinds of medicine, Polygoni Multiflori Radix and Cynanchi Wilfordii Radix. The levels of bone mineral density, osteocalcin, ALP, phosphorus, calcium in serum, calcium, phosphorus in urine, calcium, phosphorus, ash weight of bone, body weight and uterus weight were measured. Results : The levels of spinal bone mineral density was significantly increased in comparison with OVX group at 6 weeks in Polygoni Multiflori Radix group. The levels of serum ALP showed significant decrease in comparison with OVX group at 3 weeks in Polygoni Multiflori Radix group, and showed significant decrease in comparison with OVX group at 3, 6 weeks in Cynanchi Wilfordii Radix group. The levels of serum phosphorus showed significant decrease in Comparison with OVX group at 3, 6 weeks in Polygoni Multiflori Radix and Cynanchi Wilfordii Radix group. The levels of femoral and fibula-tibial calcium showed significant increase in comparison with OVX group in Polygoni Multiflori Radix and Cynanchi Wilfordii Radix group. The levels of femoral phosphorus showed significant increase in comparison with OVX group at 3 weeks in Polygoni Multiflori Radix and Cynanchi Wilfordii Radix group. Conclusions : Reviewing these experimetal results, it appears that Polygoni Multiflori Radix and Cynanchi Wilfordii Radix have efficacy on prevention of osteoporosis. And further study should be conducted to illustrate in depth the curing osteoporosis.

경화제 주입에 의한 치핵치료의 후유증

이동식,심민철,김재황 대한대장항문학회 1997 Annals of Coloproctolgy Vol.13 No.3