Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

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.

역행적 골수정 삽입술을 이용한 대퇴골 과상부 골절의 치료

권진우,신승호,조원호,성기호,김기환,손경태,이상훈,박세원,배종문,권태우 대한골절학회 2003 대한골절학회지 Vol.16 No.4

Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-kB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1

( Jae Ho Choi ),( Sun Woo Jin ),( Eun Hee Han ),( Bong Hwan Park ),( Hyung Gyun Kim ),( Tilak Khanal ),( Yong Pil Hwang ),( Minh Truong Do ),( Hyun Sun Lee ),( Young Chul Chung ),( Hee Suk Kim ),( Tae 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Purpose: The consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells. Methods: Mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism. Results: CKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells. Conclusion: We suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.ⓒ2014 Elsevler Gmbh. All rights reserved.

키넥트 센서를 이용한 고령자 대상의 선자세 균형능력 평가

양승태(Seung-Tae Yang),강동원(Dong-Won Kang),서정우(Jeong-Woo Seo),김대혁(Dae-Hyeok Kim),김태호(Tae-Ho Kim),최진승(Jin-Seung Choi),탁계래(Gye-Rae Tack) 대한전기학회 2017 전기학회논문지 Vol.66 No.2

Portable low-cost Kinect sensor was used to analyze standing balance ability of the elderly. Eighty subjects who can walk alone and have a normal cognitive level participated in this experiment. Based on Berg Balance scale (BBS) test with 52 points, subjects were divided into Healthy older (HO: 46 persons, BBS: 53.80 ± 1.19) and Impaired older (IO: 34 persons, BBS: 49.06 ± 2.03) group. Each subject performed 30 seconds four different standing balance tests (EO: Eyes Open, EC: Eyes Close, EOf: Eyes Open on foam, ECf: Eyes Close on foam). Five variables (Mean distance, Range of distance, Root mean square, Mean velocity, 95% ellipse area) were calculated from the hip joint center movement of Kinect sensor. Results showed that there were significant differences between groups for four different standing tests. Calculated variables from kinect sensor showed significant correlation with BBS score. Especially, mediolateral mean distance, mediolateral root mean square, mediolateral range of distance and 95% ellipse area showed discriminative ability for all tests. Mean values of variables of IO were higher than those of HO, which means the decreased balance ability in IO compared with HO. Therefore, it was possible to estimate simple balance assessment of the elderly using portable low-cost Kinect sensor.

'1998 한국인 우울증 선별의 날' 참가자들의 사회인구통계학적 특성과 우울증 선별검사 결과

한상익,이성필,고효진,박원명,장계호,유태열,전태연,채정호,방승규,김광수,최보문,이정태,백인호 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.5

연구목적 : 1998년 정신건강의 날 기념 한국인 우울증 선별의 날 행사에 자발적으로 참여한 참가자들의 사회인구 통계학적 특성을 분석하고 우울증 선별검사 결과를 평가하기 위하여 본 연구를 시행하였다. 방 법 : 8개 병원에서 얻어진 619명의 자료를 사용하여 선별검사로 밝혀진 우울증의 유병율과 사회인구통계학적 특성 및 응답자의 정신과적 치료를 포함한 과거력 등을 조사하였다. 결 과 : 우울증 척도 점수는 응답자 전체 평균 57.5±13.8로 경도의 우울 증상이 있는 것에 해당되었다. 전체 응답자의 69.5%(430명)가 최소한 경도 이상의 우울 증상을, 43.1%(267명)가 중등도 이상의 우울 증상을, 18.4%(114명)가 고도의 우울 증상을 보였다. 고도의 우울 증상이 있는 응답자의 56.8%와 중등도의 우울 증상이 있는 응답자의 63.9%가 정신과 치료를 받은 적이 전혀 없었다. 나이가 29세 이하인 것과 전임근무 중인 직업상태는 각각 나이가 60세 이상인 것과 직업이 없는 것에 비교하여 우울증으로부터 보호하는 인자임을 시사하였다. 결 론 : '1998 한국인 우울증 선별의 날' 행사를 통하여 많은 우울증 환자들을 선별해낼 수 있었고, 이들의 우울 증상은 몇몇 사회인구통계학적 특성과 유의한 관계가 있음을 확인하였다. 우울증 선별의 날 행사를 통한 우울증에 대한 교육과 우울증 선별검사는 치료받지 못하고 있는 우울증 환자 및 기존의 치료 중인 환자 모두에게 유용한 프로그램임을 알 수 있었다. Objectives : This study was performed to analyze the sociodemographic characteristics of participants in '1998 Korean Depression Screening Day' and to evaluate the results of the screening test. Methods : By using the survey results of 619 volunteers from 8 hospitals, the authors examined the prevalence of depression detected at the screening test and sociodemographic characteristics and the psychiatric treatment history of respondents. The assessment measure was the Zung Self-Rating Depression Scale. Results : The mean depression score of all participants was 57.5±13.8 and it came under mild depression. Of all participants, 69.5%(N=430) had at least mild depressive symptoms, 43.1%(N=267) had at least moderate symptoms, and 18.4%(N=114) had severe symptoms. Never have 56.8% of respondents in the severely depressed range and 63.9% of those in the moderately depressed range had psychiatric treatment. The results suggest that the age group of 29-year-old or younger(relative to 60-year-old or older group) and full-time employment status(relative to unemployment) are protective factors of depression. Conclusions : By '1998 Korean Depression Screening Day', many depressed patients were detected and their depressive symptoms had statistically significant relationships with some sociodemographic characteristics. The results suggest that the education and screening test programs for depressive illness facilitated by Depression Screening Day are useful to the patients regardless of being under current treatment or not.

서울의 PPNG 발생 빈도(1991-1992)

김재홍,윤기범,박평원,김영진,전경민,김영태,김중환,곽호,구상완,송민석,유옥,지혜구,김동원,문상은,박영립,정승호,성범진,성순제,엄주용,황정열,이기홍,이주협,전태진 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.1

The prevalence of PPNG among pretreated gonorrhea cases isolated at the STD clinic of Choong-Ku Public Health Center in Seoul has been studied and reported annually since 1981. In 1991, 123 strains of N.gonorrhoeae were isolated, among which 58(47.1%) were PPNG. In 1992, 98 starains of N.gonorrhoeae were isolated, among which 51(52.0%) were PPNG. In all, 109(49.3%) strains were found to be PPNG among 221 strains isolated between 1991-1992. The prevalence of PPNG in Seoul showed increased tendency till 1989, thereafter, it has been stationary or slightly decreasing.

절연물층을 확산시킨 (Ba0.5, Sr0.5)TiO₃박막의 전류-전압 특성

진병태,김진철,김명호 國立 昌原大學校 産業技術硏究所 1998 産技硏論文集 Vol.12 No.-

The mixture of PbO-Bi₂O₃-B₂O₃(PBB) phase was formed in the Ba0.5Sr0.5TiO₃(BST) film and the effects of PBB phase on the dielectric properties of the BST film were investigated. The amorphous PBB layer was deposited on the BST film using rf magnetron sputtering and diffused into the film by heat treatment. The PBB phase in BST film was identified by energy dispersive spectrometer (EDS). Dielectric properties of BST film were significantly improved after the diffusion of PBB. The leakage current density of BST film decreased from 3.24×10(-5) A/㎠ to 9.45×10(-8) A/㎠ at 1.5 V and the dielectric constant increased from 238 to 533. These results show that the formation of insulating metal oxide in the ferroelectric film can improve the dielectric properties of the film.

양압력을 고려한 중력식 콘크리트 댐에 대한 LEFM 해석

진치섭,이영호,엄장섭,김태완 부산대학교 생산기술연구소 2000 生産技術硏究所論文集 Vol.59 No.-

댐 제체와 지반 접촉 경계면 사이에 작용하는 양압력의 모델링은 중력식 콘크리트 댐의 해석시 중요하게 고려된다. 본 연구에서는 양압력의 작용에 따른 중력식 콘크리트 댐의 균열선단 부근의 음력확대계수를 표면적분법을 이용하여 계산하였다. 또한 자중, 월류수압 및 균열면에 작용하는 수압도 함께 고려 하였다. The modeling on uplift pressure on the foundation of a dam on which it was constructed, and on the interface between the dam and foundation is a critical aspect in the analysis of concrete gavity dams. The evaluation of stress intensity factor at the crack tip of concrete gravity dam due to uplift pressure effect by surface integral method is performed in this study. The effects of borty force, overtopping pressure and water pressure on the crack-face are also considered in this study.