제2형 당뇨병 동물모델인 OLETF 쥐에서 장기간 라미프릴 투여가 내당능 및 췌도 베타세포에 미치는 효과

고승현,윤건호,김명미,안유배,송기호,유순집,손현식,차봉연,이광우,손호영,강성구 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:최근 소개된 HOPE(Heart Outcomes Prevention Evaluation)study의 결과에 의하면, 심혈관질환이나 이에 대한 위험인자가 1가지 이상인 9,541명을 대상으로 안지오텐신 전환효소 억제제의 일종인 라미프릴을 투여하여 사망율과 뇌졸증, 심부전, 당뇨병 합병증이 개선되었을 뿐 아니라 다른 항고혈압제에 비해 새롭게 당뇨병으로 진단되는 환자가 줄었음을 보고한바 있다. 이에 저자들은 라미프릴(ramipril)을 제2형 당뇨병 동물모델에 장기간 투여함으로써 당뇨병을 예방하거나 고혈당 상태 또는 인슐린 감수성을 개선시킬수 있는지를 알아보고자 하였다. 방법:생후 24주된 체중 400∼450g의 OLETF와 LETO 쥐를 대상으로 6개월간 라미프릴 경구투여 하였고 혈압, 24시간 단백뇨 및 인슐린 내성검사를 시행하였다. 6개월 이후로는 8주간 투여군과 대조군의 체중을 비슷하게 맞추어 내당능 상태를 평가하였고 이후 다시 8주간 고농도 포도당을 투여하였다. 경구당부하검사를 시행한 후 희생시켜 조직표본을 만들어 guinea pig anti­human insulin 항체로 염색후 DAB로 발색하여 point count 법으로 베타세포를 정량하였고, 면역염색으로 췌도의 변화와 섬유화의 정도를 관찰하였다. 결과:라미프릴을 6개월간 투여하였을 때 OLETF 쥐에서 1)체중 증가가 적었으며 2)경구 당부하검사시 포도당하 면적은 의미있게 감소하였고 3)인슐린 내성검사상 Kitt가 증가되는 경향을 보였으며 4)수축기, 이완기 혈압과 24시간 단백뇨양이 의미있게 감소하였고 5)체중을 맞추면 내당능 상태가 비슷해졌다가 고농도 포도당 주입시 다시 포도당하 면적이 대조군에서 더 증가되었다. 라미프릴 투여군에서 췌도변형 및 파괴와 탈과립, 췌도내 섬유화가 감소하였다. 결론:본 실험에서는 인슐린 비의존성 당뇨병 동물 모델인 OLETF 쥐에서 당뇨병 발생 이전 단계부터 장기간 라미프릴을 투여할 경우 체중증가가 적었고, 투여군과 대조군의 체중을 맞추었을 때는 내당능상태의 차이가 없아가 고혈당 투여시 다시 투여군과 대조군에서 의미있는 차이를 보였다. 라미프릴 투여가 베타세포의 기능면에서 이로운 효과를 보일 것으로 생각되었다. 따라서 비만한 환자에서 안지오텐신 전환효소 억제제의 장기투여는 단백뇨 감소, 혈압강하 효과 이외에 체중증가의 억제 및 당뇨병 발생을 억제할 가능성을 시사한다. Background : In a Heart Outcomes Prevention Evaluation HOPE study, ramipril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, significantly reduced the death rates the number of myocardial infarctions, strokes, heart failure as well as the risk of complications related to diabetes and of diabetes itself. However, it is known that ACE inhibitors improve glucose tolerance or insulin sensitivity or reduce the incidence of diabetes. Methods : 24 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 400 ~ 450 g were used in this study. 4 groups of rats were examined in parallel for 40 weeks. The OLETF rats were randomized for treatment with an aqueous solution of ramipril (5 mg/Kg) daily [OL (RMP), n=10)] and with saline [OL (CON), n=10)]. The LETO rats were also randomized in the same was as the OLETF rats (LT(RMP), n=10, LT (CON), n=10). The blood glucose level, body weight, systolic and diastolic blood pressure was assessed every month. At 3 and 6 months, the 24hrs urinary protein concentration was measured, and as insulin tolerance test and oral glucose tolerance test were conducted in all experimental groups. After 6 months, the body·weight was matched for 2 months in each corresponding group. Subsequently, a 15% sucrose loading was done for 2 months. After the glucose tolerance test, the pancreas was excised and immuno histochemical staining was conducted for insulin to quantify the beta cell mass by a point-counting method. In addition, the islet morphology was evaluated in the pancreas. Results : Ramipril treatment for a period of 6 months improved the 2hr blood glucose level, the area under the glucose curve in the oral glucose tolerance test, insulin sensitivity in addition to lowering significantly systolic and diastolic blood pressure and 24hrs urinary protein level significantly in OLETF rats. Of note, a lower weight gain was observed in both the ramipril-treated animals at 6 months. After weight matching, the AUC g and 2hr blood glucose level values were similar between the corresponding groups, but a 15% sucrose loading worsened the AUC g value. Histologically, the islets were less disorganized and the extent of fibrosis was lower in the ramipril-treated OLETF rats in the trichrome stain. Conclusion : Long-term treatment of ramipril, a long acting angiotensin-converting enzyme inhibitor may be useful for suppressing weight gain and proteinuria in addition to having a protective effect on the islet to harmful stimuli such as hyperglycemia (J Kor Diabetes Asso 25:469~482, 2001).

Anisotropy of the coherence length from critical currents in the stoichiometric superconductor LiFeAs

Koń,czykowski, M.,van der Beek, C. J.,Tanatar, M. A.,Mosser, V.,Song, Yoo Jang,Kwon, Yong Seung,Prozorov, R. American Physical Society 2011 Physical review. B, Condensed matter and materials Vol.84 No.18

노인이 지각한 사회적 지지가 자존감에 미치는 영향

유양경,고성희,김귀분,정승희 성인간호학회 2004 성인간호학회지 Vol.16 No.1

Purpose: This study was done to identify the degree that perceived social support effects the self esteem of the elderly. Method: A structured questionnaire was administered to 203 elderly subjects from April 2003 to June 2003. The data were analyzed with an SPSS program for descriptive statistics, Pearson's correlation coefficients. t-test, ANOVA, and stepwise multiple regression. Result: The level of social support was moderate; family support received the highest score among sources of support. In types of support, appraisal support was the highest score and material was the lowest. The level of self esteem was also moderate. The score of social support showed a slightly high positive correlation with self esteem. In general characteristics, several variables were significantly related to self esteem. The most powerful predictor of self esteem was material support by family and the variance explained was 19.6%. A combination of material support by family, informational support by relatives, perceived economic status, perceived health status, and having a subject to depend on accounted for 39.8% of the variance in self esteem of the elderly. Conclusion: To increase the self esteem of the elderly, it is necessary to consolidate material support by family.

Heligmosomoides polygyrus 감염 마우스의 면역반응 잠재력

하대유,고유승,한병갑 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.2

Heligmosomoides polygyrus(=Nematospiroides dubis) is gastrointestinal parasitic nematoda which is common parasite of wild rodents in North America, Western Europe and the CIS. The experimental infection with this parasite has been studied extensively in models of host-parasite interaction. The present study was undertaken to investigate the effect of H. polygyrus infection on the humoral and cellular immune responses in mice. It was found that H. polygyrus infection suppressed delayed-type hypersensitivity(DTH) to SRBC, contact hypersensitivity to dinitroflurobenzene (DNFB) and hemagglutinin response to SRBC. Surprisingly, H. polygyrus infection suppressed active systemic anaphylaxis(ASA) induced by ovalbumin(OVA), but elicited marked increase of the total IgE antibody and total IgG production compared with uninfected mice. In a histological examination of the mucosal mast cell(MMC) response in vivo in ICR mice, H. polygyrus infection elicited a enhance MMC response 14 days post-infection, but did not show any difference 21 days post-infection, but did not show any difference 21 days post-infection compared with uninfected controls, suggesting mucosal mastocytosis response may depend on certain stage of life cycle of H. polygyrus. Taken together, the present study strongly suggested that H. polygyrus infection in mice in-creased the total IgE and IgG antibody production, but suppressed cellular immune response to SRBC and DNFB, hemagglutinin respose and OVA-induced anaphylaxis, and that mucosal mastocytosis may be decreased or increased depending on certain stage of life cycle H. polygyrus.

Heligmosomoides polygyrus 감염 마우스의 비장세포로 부터 만든 Conditioned Supernatant의 면역억제작용

하대유,한병갑,김명선,고유승 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.3

Heligmosomoides polygyrus is gastrointestinal parasitic nematoda which is common parasire of wild rodents. The experimental infection with this parasite has been studied extensively in models of host-parasite interaction. The present study was undertaken to investigate both the effects of administration of conditioned supernatant or conditioned medium(CM) prepared from H. polygyrus-infected mice on the humoral and cellular immune responses in mice. Normal conditioned supernatant(NCM) was prepared from uninfected mouse splenocytes stimulated with Con A. Supematants conditioned by Con A-stimulated splenocytes of H. polygyrus -infected mice were prepared on different days post-infection, namely on day 6(HCM-D6), day 14 (HCMD14) and day 18 (HCM-D18) post-infection with H. polygyrus L3 larvae. Effects of NCM, HCM-D6, HCM-D14 and HCM-D18 on delayed-type hypersensitivity(DTH) to sheep red blood cells (SRBC), contact hypersensitivity to dinitrofluorobenzene (DNFB), hemagglutinin response to SRBC, ovalbumin (OVA)-induced active systemic anaphylaxis(ASA), and anti-OVA specific IgE were investigated. Effect of anti-IL-4 antibody (11B11) on immunoinhibitory action of HCMD18 in OVA-induced ASA was also investigated. It was found that the administration into mice of HCM-D6, HCM-D14 or HCM-D18 significantly suppressed DTH to SRBC, contact hypersensitivity to DNFB, hemagglutinin response compared with NCM. The degree of immunosuppressive activity of HCM was less marked in HCM-D6 than HCM-D14 and HCM-D18. Interestingly, HCM-D18 prepared from ICR mouse strain also showed the profound suppression of OVA-induced ASA in BALB/c and C57BL/6 mouse strains as well as in ICR mice. ASA-inhibitory activity of HCM-D18 was Somewhat abrogated in terms of mouse mortality when mice were treated in the combination of HCM-D18 and anti-IL-4 antibody, indicating that IL-4 may play a role, at least in part, in the inhibitory activity of HCM. Taken together, the present study may be the first to demonstrate that conditioned supernatants prepared from the spleen cells of H. polygyrus-infected mice may suppress the in vivo humoral and cellular immyne responses to heterologous antigens, particularly fatal anaphylaxis induced by OVA, strongly suggesting that

당뇨병과 동반된 화농성 간농양의 임상상 및 예후인자

오은숙,강무일,이원영,오기원,임동준,이소영,이정민,고승현,김성래,안유배,손현식,윤건호,차봉연,이광우,손호영,강성구 대한당뇨병학회 2000 임상당뇨병 Vol.1 No.1

연구배경: 감염질환은 혈관질환과 함께 당뇨병의 중요한 사망원인의 하나이며, 혈당조절이 불량할수록 감염 빈도가 증가됨은 잘 알려져 있다. 간농양의 발생이 있어서도 당뇨병은 중요한 기저질환 중의 하나이다. 일반적으로 간농양의 가장 흔한 원인균은 Escherichi coli라고 알려져 있으나, 최근 당뇨병을 가진 간농양 환자에서 Klesiella pneumoniae의 검출이 증가되고 있다. 또 최근 연구에 의하면 K.pneumonie가 간농양의 가장 흔한 원인균이며, K. pneumoniae에 의한 간농양은 K.pneumoniae 이외의 균주에 의한 간농양보다 당뇨병과 밀접히 관련되어 있다고 보고된 바 있다. 이에 저자들은 간농양 환자를 대상으로 당뇨병환자의 빈도를 알아보고, 그 원인균 및 특징을 비당뇨병 환자들의 경우와 비교해 보고자 하였다. 방법: 1992년 1월부터 1999년 6월까지 방사선학적 검사 혹은 수술에 의해 간농양이 확인되거나, 경피적 천자나 수술을 통한 배농액 배양, 혹은 혈액 검사에서 원인균이 증명된 182명의 환자를 대상으로 후향적 임상고찰을 실시하였다. 결과: 화농성 농양을 가진 167명의 환자(남:94명, 여:73명)중 당뇨병을 가진 환자는 54명 (남:30명, 여:24명)으로 32.3%를 차지하였다. 환자의 평균나이는 당뇨군에서 62.1 ± 13.4세, 비당뇨군에서는 55.1 ±15.5세로 당뇨군에서 높았으며(p=0.0021), 남녀간의 평균나이 비교 시 두 군 모두 여성의 나이가 의미있게 높았다. 비당뇨군에 비하여 당뇨군의 경우 저알부민혈증의 빈도와 aspartate transaminase가 증가되어있었다. 원인균주는 K. pneumoniae (당뇨군54%, 비당뇨군 39.1%), E. coli(당뇨군 17.5%, 비당뇨군 18.8%), Pseudomonas aeruginosa, Streptococcus viridans, Enterococcus 순이었으며 두 군간의 의미는 차이는 없었으나 K. pneumoniae의 경우 다른 균종에 비해 단독감염의 빈도가 높았다(82.8%). 사망률은 당뇨군에서 16.7%, 비당뇨군에서 7.1%로 당뇨군에서 의미있게 높았으며(p=0.019), 당뇨군에서의 사망환자는 모두 패혈증이 동반되어 있었다. 당뇨환자의 사망군은 생존군에 비해 당뇨병 이환기간이 길고 혼합감염의 빈도가 높았다(p=0.046). 검사실 소견에서는 총 빌리루빈 및 알카리성 포스파타제의 증가가 관찰되어 있었다. 결론: E. coli가 간농양의 주된 원인균이라는 기존 보고와는 달리 당뇨군과 비당뇨군 모두 K. pneumoniae가 간농양의 주된 원인균이었다. 또한 당뇨 유병기간이 길고 당뇨조절이 불량한 환자에서 혼합감염이며 총 빌리루빈 및 알카리성 포스파타제의 증가등과 같은 위험인자가 존재할 경우 사망률이 증가될 수 있으므로 이들 군에서는 적극적인 치료가 필요할 것으로 사료된다. Background: Liver abscesses are commonly associated with underlying disease, particularly diabete mellitus. The number of the liver abscesses caused by Klebslella pneumoniae in diabetic patient has been increased in Korea nowadays. This study was conducted to clarify the clinical presentation and prognostic factors of pyogenic liver abscesses, especially in diabetic patients and to determine the proportion of K. pneunomiae as a pathogen in liver abscess in Korea. Methods: Medical records of 167 patients treated for pyogenic liver abscess from January, 1992 through June, 1999 were reviewed retrospectively in detail. Major Pathogenic organism, clinical manifestations, prognostic factors, the importance of diabetes mellilus as an underlying disease and its effect on clinical features and prognosis were analyzed. Results: Among 167 cases of pyogenic liver abscess, underlying diabetes mellitus was present in 32.3%. The mean age of patients was 62.7 13.4 years in diabetic liver abscess group and 55.1 15.5 years in non-diabetic liver abscess group. Most liver abscesses were cryptogenic in origin or secondary to the billary tree diseases. The clinical presentations among the two groups were not significantly different. When compared to patients without diabetes, patients with diabetes had significantly higher proportions of hypoalbuminemia and elevated aspartate transaminase level. The most common organism of the pyogenic abscess was K. pneumoniae in both groups. Percutaneous drainage of the abscess with appropriate antibiotics was the most commonly used therapeutic modality in liver abscess. The mortality rate of diabetic liver abscess is 16.1 % and 7.1% in nondiabetic liver abscess. Complications, especially septicemla, were found more frequently in patients with diabetes than in patients without diabetes (64.8% vs 28.3%, septicemia : 31.5% vs 9.7%). The factors influencing mortality in the diabetic liver abscess were disease duration, mixed infection, presence of septicemia, elevated bilirubin and alkaline phosphatase. Conclusions: In contrast to prior report that the E. coli was the most common pathogen in liver abscess, we found that K. pneumoniae was the most common organism cultured in liver abscess. Diabetic patients have more complications and higher mortality than patients without diabetes. Early detection and proper treatment are needed to improve the outcome for diabetic patient with liver abscess.

Treatment-Plan Evaluation Using the Dose Quality Factor (DQF) for Dynamic Conformal Arc (DCA)-based Radiosurgery on Patients Presenting with an Intracranial Tumor

Seung Hoon Yoo,Byung Jun Min,Kum Bae Kim,Sungho Cho,Eun Ho Kim,Jeong Hoon Park,Won-Gyun Jung,Geun Beom Kim,Seung Young Ko,Hyun Soo Shin,Sei Kyung Chang,Ho Jin Jeong,Dong Ho Shin,Kwan Ho Cho 한국물리학회 2016 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.69 No.12

The aim of the present study was to find the optimum dynamic conformal arc (DCA)-based radiosurgery conditions for treatment of patients with intracranial tumors. DCA plans were generated on a commercial treatment-planning system (BrainSCAN v.5.31) for various beam-number and gantry-angle combinations by using computed tomography (CT) scans to delineate the planning target volume (PTV) and the organs at risk (OARs). To evaluate planning quality related to the various planning conditions, we analyzed the dose quality factors (DQFs) for 22 patients as a function of the number and the total angle of arcs related to the target volume, which were determined on the basis of patient-specific features. When the total angle of arcs was less than 250, the DQF values were under 0.98 (worst group). When the total angle of arcs was more than 350 degrees, the DQF values were maximized, and the highest DQF values (best group, DQF > 0.995) occurred in the range between 50 and 120/cm3 for the total angle/target volume condition. In this optimal range of angle/volume, the asymmetric distribution of the arcs resulted in decreased DQF values. For a relatively large target volume (more than 10 cm3), the DQF values were lower than these for a relatively small target volume (less than 10 cm3). Re-planning results showed that the planning quality could be improved using optimized planning conditions. We expect that this study will provide a basis for the evaluation of various DCA conditions prior to actual planning and treatment.

Interleukin-2 Inhibits Secretin-Induced Bile Secretion in Cholangiocytes

Yoo-Seung Ko,Seock-Yeon Hwang,Jae-Seung Park 대한의생명과학회 2013 Biomedical Science Letters Vol.19 No.2

Cholestatic liver is associated with hepatic inflammation and elevated proinflammatory cytokines. Recent studies indicate that certain cytokines can modulate bile secretion. In the present study, we have examined the role of interleukin (IL-2) on the bile secretion by a combination of study models. To examine the relevance of IL-2 on bile secretion, the expression of IL-2 and IL-2 receptor (IL-2R) of isolated normal and bile duct ligated (BDL) rats cholangiocytes was first measured by RT-PCR. In BDL rats, the expression of IL-2 and IL-2R was significantly increased compared with normal rats. To study the effect of IL-2 on bile secretion, bile flow was measured in normal and BDL rats. At the level of cholangiocytes, secretory responses of isolated bile duct unit (IBDU)s were quantified by videomicroscopy. The administrations of IL-2 had no significant effect on basal bile secretion in normal and BDL rats. There was no significant effect of IL-2 on basal bile ductular secretion as evidenced by no significant difference in luminal area of the IBDUs perfusedwith 100 pM of IL-2 from those of albumin carrier control. However, the secretin-stimulated bile ductular secretion was significantly (P < 0.01) inhibited by 34 ± 4% (normal, n = 12), 21 ± 5.3% (BDL 2 wk, n = 12) and 15 ± 5.2% (BDL 4 wk, n = 12) with the co-administration of IL-2. As with other cytokines, physiologically relevant concentration of IL-2 can significantly inhibit secretin-stimulated bile ductular secretion. These findings support the important roles of cytokines in modulating bile secretion and may contribute to the cholestasis seen in cholestatic liver diseases.

POSTERS / PW-105 : TNF-α EXPRESSION WAS INDUCED BY LEUKOTRIENES IN MACROPHAGE CELL LINE , RAW 264.7

(Yoo Seung Ko),(Youn Ja Na),(Suhn Young Im),(Hee Sook Sung),(Hwang Hee Blaise Lee) 한국생화학분자생물학회 (구 한국생화학회) 1999 6th IUBMB SEOUL CONFERENCE Vol.- No.-

Systems Metabolic Engineering of Escherichia coli for the Production of Putrescine and Proline Using Synthetic Regulatory Small RNA

Yoo-Sung KO,Minho ROH,Seung Min YOO,Sang Yup LEE 한국생물공학회 2018 한국생물공학회 학술대회 Vol.2018 No.10