Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

Lee, Eun-Mi,Lee, Young-Eun,Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Moon, Sung-Dae,Song, Ki-Ho,Ahn, Yu-Bae Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.</P><P><B>Results</B></P><P>CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.</P><P><B>Conclusion</B></P><P>Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.</P>

혼합감도 평가함수 H∞놈 최소화-다항식 접근방법

安鎬均,宋大原,朴勝圭 창원대학교 공작기계기술연구센터 1999 연구업적집 Vol.1 No.1

The Grimble's polynomial approach in the design of H∞ robust controller is applicable to adaptive control system But it can not minimize the mixed sensitivity cost function. In this paper, In this paper, we use the Youla type of controller and make it possible to minimize the mixed sensitivity cost function by using polynomial approach.

정신분열병 및 정신분열형 장애에 대한 올란자핀의 효과와 안전성

안용민,강대엽,권준수,김창윤,김철응,반건호,신영민,이기철,이동우,이중서,조현상,채정호,김용식 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.4

연구목적 : 본 다기관 공동임상연구는 국내 환자를 대상으로 새로운 항정신병약물인 올라자핀의 치료 효과와 안전성을 확인하고자 시행되었다. 방 법 : 1999년 7월부터 2000년 3월까지 국내 10개 병원에 방문한 정신분열병 및 정신분열형 장애 105명을 대상으로 비대조 개방 임상연구를 시행하였다. 중등도 이상의 정신병 증상을 지니거나, 부작용으로 약물교체가 필요한 경우 또는 기분장애 증상의 치료가 필요한 환자를 대상으로 하였다. 2∼7일간의 약물 배설기간 후에 1일 10mg의 올란자핀을 투여하였고, 이후로 3∼7일 간격으로 용량을 조절하여 총 8주간 투여하였다. 치료 효과는 PANSS(Positive and Negative Syndrome Scale), BPRS(Brief Psychiatric Rating Scale), CGI(Clinical Global Impression-Severity), MADRS(Montgomery-Asberg Depression Rating Scale), HAM-A(Hamilton Rating Scale for Anxiety)로 판정하였다. 안전성 평가는 자발적인 이상반응 보고, 활력징후와 혈액 검사 및 SAS(Simpson-Angus Scale), BARS(Barnes Akathisia Rating Scale), AIMS(Abnormal Involuntary Movement Scale)척도를 이용하였다. 결 과 : 105명중에서 85.7%인 90명이 8주간의 치료를 완료하였다. 평균 최빈 용량은 일일 16.1(±4.7)mg이었고, 종료시점에서의 BPRS전체 점수가 기저 상태에 비해 40%이상 감소된 반응군은 69.5%이었다. PANSS의 양성 증후군과 일반정신병리 뿐만 아니라 음성 증후군 소척도에서도 유의한 감소를 보였으며, 이 감소들은 치료 초기부터 나타나서 8주간 지속되었다. 43.8%의 피험자가 중등도 이상의 우울증상을 같이 지니고 있었으며, 올란자핀에 의해 MADRS와 HAM-A가 유의하게 감소하였다. 치료 기간 동안에 활력징후에는 뚜렷한 변화가 없었으나 체중은 8주간 지속적으로 증가하였다. SAS와 AIMS는 감소하였으며, 정좌불능증을 제외한 나머지 추체외로 증상의 발생비율도 낮았다. 임상적인 증상이나 징후를 동반하지 않는 ALT/SGPT의 상승을 보였지만 프로락틴을 포함하는 대부분의 혈액 검사상 뚜렷한 이상 변화는 없었다. 결 론 ; 비록 본 임상연구가 비대조 개방 임상연구로서 많은 제한점을 가지고 있지만, 올란자핀이 기존 약물에 내약성을 보이거나 기분증상을 동반하는 정신병에 치료 효과가 있었다. 그리고 기존 항정신병약물 치료시에 문제가 되었던 추체외로 증상과 고프르로락틴 혈증을 포함하는 대부분의 부작용면에서 안전성을 보여 주었다. Objective : This multicenter clinical trial was carried out to investigate the efficacy and the safety of olanzpine for the treatment of Korean patients. Mothod : 105 patients with schizophrenia and schizophreniform disorder, visited at 10 mental or university hospitals, had received an open and non-comparative treatment with olanzapine for 8 weeks. Patients had psychotic or depressive symptoms with the severity above moderate degree or intolerable side effects to previous antipsychotics. After a wash-out period of 2-7 days, 10mg olanzapine was prescribed initially to all the patients, and then the dosage could be adjusted within the range of 5-20mg/day of olanzapine by 3-7 days. Results : 90(85.7%) of 105 patients completed the 8-weeks trial and the mean modal dose of olanzapine was 16.1(±4.7%)mg/day. At the end of the trial, 73 patients(69.5%) were classified as responder, which was defined as 40% or more improvement in BPRS(Brief Psychiatric Rating Scale) score comparing to baseline. There was a significant reduction in the scores of PANSS(Positive and Negative Syndrome Scale)and subscales including negative symptom scores and CGI. Also weekly analysis showed that the reductions in scores were kept on for the whole period of the trial. 43.8% of all the patients had depressive symptoms at the baseline and total scores of MADRS(Montgomery-Asberg Depression Rating Scale) and HAM-A(Hamilton Rating Scale for Anxiety) were also reduced after the trials. Vital signs revealed no clinically significant changes but continuous weight gain was observed during the treatment with olanzapine. The scores of SAS(Simpson-Angus Scale) and AIMS(Abnormal Involuntary Movement Scale) for assessing the EPS(extrapyramidal symptoms)and tardive dyskinesia respectively were significantly decreased and only a few patients reported EPS as adverse events. Although mild and clinically non-significant of ALT/SGPT was observed, most laboratory parameters including plasma prolactin level showed to significant changes during the trial. Conclusions : Although this trial had many limitations because it was a non-comparative and open study, olanzapine showed high efficacy on the positive, negative and depressive symptoms in schizophrenia and schizophreniform disorder.In addition to that, olanzapine showed a substantially favorable safety profile, such as low incidence of EPS and hyperprolactinemia.

온쓸개관을 묶은 집토끼 위날문점막의 미세구조 연구. : Ⅰ. 날문부 표면점액세포 Ⅰ. Pyloric Surface Mucous Cell

박경호,오승종,고정식,안의태,박대균,정은주 순천향대학교 교수학습개발센터 2004 Journal of Soonchunhyang Medical Science Vol.10 No.3

The purpose of this study was to examine the ultrastructural characteristic of the normal pylorus mucosa, and their structural changes induced by the ligation of common bile duct of the rabbit. Common bile duct ligation probably causes the dysfunction of the pyloric surface mucous cells that results in delayed mucous formation and secretion, but recovered mucous secretory activity is recovered on the late stages.

건식경량벽체의 내충격성능 평가방법에 관한 연구 (Ⅰ) : 인간이 벽체에 가하는 충격하중의 분석을 위한 실험 및 고찰 An Experiment to Analyze the Human Impact Load Applied to Framed Walls

신윤호,안정업,김대희,최수경 대한건축학회 2003 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.23 No.1(구조계)

The purpose of this study is to establish an evaluation method of fracture of light-weight framed walls by human impact load. In this paper, part (I), we analyzed human impact load applied to framed walls. At first, we made original measuring equipment of impact load, and carried out the experiment on human impact load in various action. After the experiment, we extracted the essential characteristics. And grasped the property of human impact load systematically based on the relation between maximum load and load velocity.

공업용 접착제 증기 흡입이 흰생쥐 기관상피에 미치는 영향 : 조직화학적 및 미세구조적 연구

박경호,박삼열,고정식,안의태,박대균 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

Industrial glues, known as Bonds in Korea, contain many kinds of organic solvents, and glue sniffing of youths became one of the social problems in Korea. Mixed exposures to solvents by glue sniffing may induce chronic toxicities different from those induced by exposures to the solvent of single component. In this study, toxicological insult of the inhalation of glue vapor on the primary target organ, the tracheal epithelium of the respiratory system was morphologically worked out. Vapor samples of organic solvents were collected for analysis, and the components found were aceton, n-hexane, methyl cyclopentane, c-hexane, and toluene by gas mas. In order to inhale the organic solvents of adhesives to the mouse, experimental animals were exposed to vapors of the glues(acetone 5212 ppm, n-hexane 139 ppm, c-hexane 3757 ppm, methylcyclopentane 1820 ppm, and toluene 2.2 ppm) in a chamber for 20 min/day for 3, 5, 7, 14 consecutive days, in a whole body inhalation chamber. Control groups were exposed to room air. Animals were sacrificed and tracheal tissues were collected and fixed in 10% neutral formalin for light microscopy and in 2.5% glutaradlehyde - 1.5% paraformaldehyde for transmission electron microscopy and in 2.5% glutaraldehyde for scanning electron microscopy. The results are as follows : 1. In the tracheal epithelium of a normal mouse, ciliated cells, nonciliated cells and basal cells were found, but goblet cells and submucosal glands were not found. 2. In the tracheal mucosa of a normal mouse, alcianophilic bands were detected, but PAS positive bands were not found, but alcian blue-PAS positive cells were found in the mucosae exposed to glue vapor for 7 days and 14days. 3. Distributing of ciliated and nonciliated cells in the epithelium were roughly comparable during experimental periods; the longer the experimental period(2 week), higher the percentage of non-ciliated cells. 4. The mouse of organic solvent inhaled group showed three distinct forms of nonciliated cells, which were apparently transitional types between nonciliated cells and ciliated cells. It is suggested that the role of the nonciliated cell might be a developmental functioning involved in the epithelial cell turnover. Nonciliated cells show a great deal of plasticity; change to ciliated cells during the early phase; and revolving of nonciliated cells during the repopulation phase after injury. The results suggest that ultrastructural morphologic changes in tracheal epithelia may occur following glue sniffing, and those structural changes were analysed as an adaption to the environment.

국산 DAF 펌프의 기포특성

안대명,이창한,최윤찬,조석호,안갑환,김성수 대한상하수도학회 2002 상하수도학회지 Vol.16 No.4

The paper introduces a domestic pump designed for dissolved air flotation (DAF). In the paper, the difference in performance between the domestic DAF pump and conventional pressure saturator is explained using the characteristics of air bubble released. The size distribution of air bubbles released from DAF pump is measured by image analyzer and particle size analyzer. And the mean diameter of bubbles is 43μm. The results are similar to that of pressure saturator. The air volume concentration in the water of domestic DAF pump and pressure saturator are 40 and 70% of theoretical amounts. In DAF system used domestic DAF pump, the removal efficiency of turbidity is 70%.

성별판별을 위한 한국인 성인 방패연골의 판별분석

박대균,안의태,고정식,박경호 순천향대학교 교수학습개발센터 2004 Journal of Soonchunhyang Medical Science Vol.10 No.3

방패연골은 목뿔뼈 바로 아래 위치하며 후두부를 구성하는 연골 가운데 가장 큰 연골이다. 본 연구는 한국인 방패연골의 형태분석을 통해 얻은 결과를 이용하여 성별판별을 할 수 있는지 알아보고자 하였다. 20대이상 한국인에서 109(남자69, 여자 40)개의 방패연골을 대상으로 26가지 항목을 계측하여 통계학적으로 검증하여 다음과 같은 결과를 얻었다. 1. 방패연골너비, 방패연골높이, 방패연골길이, 연골판높이 등은 남자의 계측치가 컸다 (p<0.01). 2. 연골판각, 방패연골아래뿔각, 위방패패임각 등은 여자의 게측치가컸다. (p<0.01). 3. 방패연골길이와 연골판높이 항목을 이용하여 남녀판별함수를 얻었다. 이상의 결과에서 한국인 방패연골은 성별에 따라 차이가 있었으며, 20대 이상 한국인의 경우 방패연골의 형태분석에 의해 성별을 판별할 수 있을 것이다.

토끼 눈물샘에서 Nitric Oxide Synthase의 면역조직화학적 연구

박경호,이석호,고정식,안의태,박대균 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

Endogenous nitric oxide(NO) has been known to regulate many physiological and pathological process, especially the salivary secretion and glandular blood flow. However, nitric oxide synthase(NOS) responsible for NO synthesis has not been well studied in rabbit lacrimal gland. The present study was performed to investigate the distribution of nitric oxide synthase isoforms(endothelial, neuronal, and inducible NOS). Immunohistochemistry, using monoclonal mouse anti-endothelial NOS, anti-neuronal NOS, and anti-inducible NOS, was performed in inferior lacrimal of the rabbit. Endothelial NOS(eNOS)-positive immunoreactivities were observed in arterial endothelia, intralobular ducts and interlobular ducts of the inferior lacrimal gland of the rabbit. eNOS-positive immunoreactivities were most prominent in the interlobular and intralobular ducts. Immunoreactivities were well concentrated in cytoplasm of columnar epithelial duct cells. However, weak eNOS-positive immunoreactivity was observed in the intercalated ducts and vascular endothelial cells. Neuronal NOS(nNOS)-positive immunoreactivity was seen in the nerve fibers of inferior lacrimal gland. nNOS-positive immunoreactivy was not detected in duct systems or in acinar cells. Inducible NOS-positive immunoreactivity was not seen. Especially, the expression of the nNOS in the nerves of lacrimal gland suggest that NO may play a role in modulating tear production. These results reveal the presence of eNOS and nNOS in the lacrimal gland of the rabbit, which may be related with regulation of the glandular secretion and blood flow through the gland.

Mitomycin C가 생쥐 콩팥소체의 미세구조에 미치는 영향

고정식,안의태,박경호,박대균 순천향대학교 교수학습개발센터 2004 Journal of Soonchunhyang Medical Science Vol.10 No.3

The experiment was performed to study the morphological responses of the renal glomeruli of the mice after administration of mitomycin C. Healthy adult mice weighing about 25gm each were divided into normal and experimental groups. Mitomycin-C(400㎍/kg) was injected subcutaneously to the animals every other day, and animals were sacrificed at 4 days or 6 days following the first injections. Pieces of tissues were taken from renal corticies, prefixed with 2.5% glutaraldegyde- 1.5% paraformaldehyde(0.1M Millonig's phosphate buffer, pH 7.), and followed by post-fixation with 1% osmium tetroxide(0.1M Millonig's phosphate buffer, pH 7.3). Fixed blocks were dehydrated with alcohol and acetone, embedded in araldite mixture, cut with LKB V-ultrotome. The ultratihin sections stained with urany1 acetate and lead cirtrate were observed with a JEM 100CX-Ⅱ electron microscope. In the fourth and seventh day following the first injection of mitomycin C, components of the renal glomeruli of the mice are looked compact since they were filled with the widened the mesangium, and showed narrowing lumen of glomerular capillaries and of urinary spaces. The electron densities of the lamina rara interna and the lamina rara externa were similar to the density of the lamina densa and the expanded lamina rara interna were often seen. and the cisternae of the rough endoplasmic reticulum of the podocytes were slightly swollen, whereas flattened cisternae of the Golgi complexes were frequently observed. From the above results, it was suggested that although small amount of mitomycin C(400ug/Kg) may give damages on the fine structure of the renal glomeruli of the mice.