Ultrasound-Triggered Drug Release of Hydroxyapatite Coated Liposomes

조성근,위태인,하정,조선행,한건,한희동,신병철,Cho, Sung Keun,Wee, Tae In,Ha, Jeung,Cho, Sun Hang,Han, Kun,Han, Hee Dong,Shin, Byung Cheol Korean Chemical Society 2013 대한화학회지 Vol.57 No.4

리포솜은 표적 약물을 봉입하여 병소에 안전하게 전달할 수 있는 약물전달체로서 연구되고 있다. 그러나 일반적인 리포솜은 표적부위에서 약물방출이 제한적인 문제점이 있다. 따라서 본 연구에서는 리포솜의 안정성을 향상시키고 표적부위에서 외부 초음파로부터 약물의 방출을 극대화시키기 위하여 하이드록시아파타이트(hydroxyapatite, HA)가 코팅된 리포솜을 개발하였다. 대조군 리포솜은 인지질과 콜레스테롤을 이용하여 제조하였고, 대조군 리포솜의 표면에 칼슘 아세테이트, 포스포릭에시드, 그리고 25% 암모니아용액을 이용하여 HA를 코팅하였다. 모델 약물로는 독소루비신을 사용하였다. HA코팅 리포솜의 크기는 120 nm 이었고, 약물봉입효율은 95% 이상이었다. 30% 혈장용액 내에서 HA코팅 리포솜의 입자크기는 일정한 상태를 유지하였으며, 대조군 리포솜은 크기가 1.4배 증가하였다. 외부 초음파 자극에 의한 리포솜으로부터 약물 방출을 유도한 후, 방출된 약물의 세포 이입율은 HA 코팅된 리포솜이 3배 이상 대조군 리포솜에 비하여 증가하였다. 본 연구에서는 외부 초음파 자극에 의하여 리포솜으로부터 약물의 방출을 극대화시키기 위한 초음파 민감형 리포솜을 개발하였고, 본 제형은 표적부위에서 약물의 방출을 효과적으로 제어하기 위한 분야에 활용이 가능할 것이다. Liposomes, which can deliver payload at target site, have been studied as drug carrier. However, conventional liposomes have limitation for drug release at target site. Therefore, we developed hydroxyapatite (HA) coated ultrasound sensitive liposomes to increase drug release at target site and to enhance stability in blood stream. Control liposome was prepared using hydrogenated soy phosphatidylcholine (HSPC) and cholesterol, and then we assessed HA coating on the surface of control liposomes using calcium acetate, phosphoric acid, and 25% ammonium solution. Doxorubicin was used as a model drug. Size of HA coated liposomes was 120 nm and encapsulation efficiency of doxorubicin in liposomes was up to 95%. Size of HA coated liposomes are not changed in 30% serum solution, however, the control liposomes was 1.4 fold increased. After ultrasound triggered drug release from liposomes, intracellular efficiency of drug released from HA coated liposomes was 3 fold increased compared to control liposomes. In this study, we developed ultrasound sensitive liposomes to enhance drug release, which will be applied in controlled drug release at disease site.

The HBV DNA Amounts in Serum Have No relationship with ALT level and Hetergeneous Population Coexits in Chronic Hepatitis B Virus Infection

Chun, Yoon-Keun,Ha, Joo-hun,Hong-Jung-Woo,Oh, Soo-Myung,Kim, Sung-Soo 경희대학교 동서의학연구소 1999 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1999 No.1

Yoon-Keun Chun¹,Joohun Ha□Hong-Jung Woo□, Soo Myung Oh□,Sung Soo Kim□ ¹Department of Molecular Biology, College of Medicine,²Department of Surgery, college of Medicine,³Department of Internal Medicine, College of Oriental Medicine,and ⁴East-Weat Medical Reserch Institute,Kyung Hee University, Seoul, Korea. The HBV DNA Amounts in Serum Have No relationship with ALT level and Hetergeneous Population Coexits in Chronic Hepatitis B Virus Infection. Proceedings of International Symposium on East-West Medicine, Seoul. 212-230, 1999. -Hepatitis B is caused by hepadnavirus. Hepatitis B virus replicates through 3.5kb pregenomic RNA intermediate which is regulated by core promoter. Pathogenesis of hepatitis B virus has been bilieved the result of host immune response. But recently many studies have reported that high level of viral replication caused by mutation in core promoter might result in severs hepatitis. But these studies were performed in vitro, not in vivo. So there is yet debate about which factor, viral of host factor, is more important in pathogenesis of hepatitis B virus. So we measured real viral replication level in 204 chronic hepatitis B patients by quantifying HBV DNA from sera by our novel PCR-based more sensitive method, and compared these results with ALT level measured from same sera, which indicates liver cell damage. Surprisingly there are no significant correlation between HBV DNA quantity and ALT level. Then we cloned core promoter region. In SSCP, we found that many viral mutants coexist in one patient. Base on SSCP result, we chose main viral core promoter type in each patients, which is thought to determine overall viral replication level in this patient. Main type of core promoter region of each 41 patients were directly sequenced. And with these we measured promoter activity by luciferase assay system and compared promoter activity with on another. We found tha there were some differences in promoter activity according to core promoter sequences. And we constructed replication-competent viral constructs with core promoter from 41 patients and Transfected these into HepG2 cell and measured HBV DNA by southern blot. There were also differences in HBV DNA quantity according to core promoter sequences. On these all results we investigated correlation between the effect of HBV core promoter on viral replication in vitro and HBN DNA quantity, ALT level from sera of each patients. We found there is no significant correlation among them. As a result, we concluded that in determining severity chronic hepatitis B patients, host factors of each patient is more important rather than replicative activity of virus itself.

바닷물 살포가 토양 화학성과 마늘 무기성분 함량에 미치는 영향

김명숙(Myung-Sook Kim),이상범(Sang-Bum Lee),김유학(Yoo-Hak Kim),강성수(Seong-Soo Kang),현병근(Byung-Keun Hyun),공효영(Hyo-Young Gong),하상건(Sang-Keon Ha) 한국토양비료학회 2011 한국토양비료학회지 Vol.44 No.6

친환경농업에 많이 사용되고 있는 바닷물을 살포하여 토양의 화학성과 마늘의 무기성분 흡수량의 변화를 조사하였다. 바닷물 원액을 토양에 살포한 직후에는 전기전도도, 치환성 나트륨, 염소이온, 나트륨 흡착비 등이 높아졌다. 그리고, 바닷물의 살포횟수가 증가할수록 토양의 전기전도도, 치환성 나트륨, 염소이온 그리고 나트륨 흡착비가 증가하였다. 바닷물로 투입된 성분들은 표토에 대부분 분포하였으며 수확기에는 심토로의 용탈이 일어나 작물이 생육하는 근권에서는 감소하였다. 그리고 바닷물 원액을 작물체에 살포했을 때 마늘 중의 무기성분인 질소, 칼슘, 마그네슘, 나트륨, 미량원소인 철, 망간, 아연 등의 함량은 줄어들었고 염소이온 함량은 처리횟수가 3회일 경우 유의성 있게 증가되었다 (p<0.05). This study was conducted at the organic farming fields which garlics were planted. The treatments were as follows; water of 3,850 L ha<SUP>-1</SUP> (Control), plots applied 1 time, 2 times and 3 times with sea water of 3,850 L ha<SUP>-1</SUP>. In 3 times sea water treatment plot, the level of EC, Exch. Na and Cl- were 1.1, 2.1, and 3.3 times higher than control plot, respectively. Due to seawater application, the contents of inorganic elements such as T-N, Ca, Mg, Na, Fe, Mn, and Zn in garlic were generally lower than Control, but not significant.

분포형 토양침식지도를 이용한 한강상류지역 토양유실 위험성 평가

박찬원(Chan-Won Park),손연규(Yeon-Kyu Sonn),장용선(Yong-Seon Zhang),홍석영(S. Young Hong),현병근(Byung-Keun Hyun),송관철(Kwan-Cheol Song),하상건(Sang-Keun Ha),문용희(Young-Hee Moon) 한국토양비료학회 2010 한국토양비료학회지 Vol.43 No.6

본 연구에서는 1:25,000 정밀토양도 등 가용한 공간자료를 이용하여 작성된 토양유실도를 이용하여 한강 상류지역 10개 중권역 108 소유역에 대하여 토양유실량 평가하고 토지이용별 토양유실 위험지역을 분석하였다. 대상유역 총 토양유실량은 895만 Mg yr<SUP>-1</SUP>으로 예측되었으며, 면적당 평균 토양유실량은 6.1 Mg ha<SUP>-1</SUP>yr<SUP>-1</SUP>이었다. 중소유역 단위로 살펴보면 남한강지역이 북한강지역의 유실량 뿐만 아니라 면적당 유실량이 더 많았다. 이는 북한강 권역의 경우 화강암 및 화강편마암이 주요 모재인 반면에 남한강 권역의 경우 토양모재가 퇴적암지대를 많이 포함있어 토양침식성 인자 (K factor)와 경사 인자 (LS factor)가 상대적으로 높고, 남한강 지역의 경우 농경지 토양이 상대적으로 많이 분포하고 있기 때문으로 판단된다. 대상유역의 토지이용별 연평균 토양유실량을 분석한 결과 산림/초지 > 밭 >> 도심/대지 >> 논 > 과수의 순로 분석 대상유역 중 10.7%를 차지하고 있는 농경지에서 유실되는 토양의 추정량은 41.3%이였으며, 이중 6.2%면적을 차지하는 밭이 40.6%으로 44.2%의 산림/초지와 비슷한 수준이었다. 한강상류지역 토양유실 위험성 평가시 분포형 토양침식지도와 항공사진을 비교한 결과 토양유실에 대한 공간인 정보를 확실하게 보여주고 있으며, 토양침식위험성은 남한강권역의 남한강 상류 (1001), 평창강 (1002), 충주댐 (1003) 권역에서 각각 토양침식위험성이 “보통”이상으로 높은 지역이 각각 8.7%, 7.9%, 7.8%로 평균인 5.9%보다 높았으며, 이에 대한 보전방안이 강구될 필요가 있고 판단된다. This study was conducted to evaluate soil erosion risk with a standard unit watershed in the upper Han river basin using the spatial soil erosion map according to the change of landuse. The study area is 14,577 ㎢, which consists of 10 subbasins, 107 standard unit watersheds. Total annual soil loss and soil loss per area estimated were 895 × 10<SUP>4</SUP> Mg yr<SUP>-1</SUP> and 6.1 Mg ha<SUP>-1</SUP> yr<SUP>-1</SUP>, respectively. A result of analysis with a subbasin as a unit showed that annual soil losses and soil loss per area in Namhan river basins was more than in Bukhan river ones. Predicted annual soil loss according to the landuse ranked as Forest & Grassland > Upland >> Urban & Fallow area > Paddy field > Orchard. Upland area covered 6.2% of the study area, but the contribution of total annul soil loss was 40.6% and that of Forest & Grassland was 44.2%. As a evaluation of soil erosion risk using the spatial soil erosion map, we could precisely conformed the potential hazardous region of soil erosion in each unit watersheds. The ratio of regions, graded as higher “Moderate” for annual soil loss, were respectively 8.7%, 7.9% and 7.8% in 1001, 1002 and 1003 subbasins in Namhan river basin. Most landuse of these area was upland, and these area is necessary to establish soil conservation practices to reduce soil erosion based on the field observation.

중기발암성시험기법을 이용한 Carbendazim의 간발암성 검색

성하정,이제봉,정미혜,이해근 한국환경독성학회 1998 환경독성보건학회지 Vol.13 No.2

Carbendazim, which is widely used fungicide, was investigated for rat hepatocarcinogenesis using a medium-term carcinogenicity bioassay. All rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i. p. and then, starting 2 weeks later, carbendazim treatment group and positive control group received carbendazim (7 mg/kg/ day) and 2-acetylaminofluorene (2-AAF, V/0, respectively, in the diet for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3 and sacrificed at week 8. Carcinogenic potential was scored by comparing the number and area per cm" of induced glutathione-S-transferase placental form (GST-P) positive foci in the liver. Carbendazim had no effect in the increase of body weight, hematological and biochemical values, and the number and area of GST-P positive foci. These results suggest that this bioassay using DEN-PH method can be useful for detection of hepatocarcinogenic potentials of pesticide.

우리나라 地方自治團體의 人口增減에 관한 硏究

하상근,전일주 진주산업대학교 2005 論文集 Vol.44 No.-

An economic development plan since 1960 made great strides in economic growth, which, in the meantime, gave impetus to industrialization and urbanization in korea. The urbanization resulted in the movement of surplus labor manpower of the rural community to cities, and a decrease in population of the rural community has brought about a shortage of manpower in the rural community. This dissertation understands on the increase and decrease of population of local government in korea during the period of 1991~2002. And unit of analysis is primary local government level. This increase and decrease of population of local government included natural increase and decrease and social increase and decrease. In the result of analysis, this study with the increase and decrease of population in korea is summarized, "seoul metropolitan region and busan, daegu, gwangju, daejeon metropolitan region increase excess" and "the others(non-seoul metropolitan) region decrease excess". And the recent pattern in the increase and decrease of population of local governments in korea has been shifted noticeably from the concentration into the capital region to the dispersion within seoul metropolitan area. Finally, there is growing tendency that primary urban communities and rural communities were decrease of population.

國立大學에서 敎授와 行政職員間의 葛藤要因分析에 관한 硏究

하상근,전일주 진주산업대학교 2003 論文集 Vol.42 No.-

정책불응의 제도적 요인분석 : 국민연금제도를 중심으로

하상근 慶尙大學校 經營行政大學院 2002 사회과학연구 Vol.20 No.2

Looking at the National Pension Law which was established in 1986 and the National Pension System which was enforced in January 1, 1988 as of today, still many people (National Pension Target Group) has a contradictory views on it. This dissertation understands the non-compliance of the national pension system as policy target group's institutional factor. Examining results of these analysis, the problems of the pension scheme itself can make the non-compliance of the target group.

인플레이션率과 株式收益率 사이의 關係에 관한 實證的 硏究

河正鎭,徐洵根,金承卓 동아대학교 공과대학 부설 한국자원개발연구소 1987 硏究報告 Vol.11 No.1

The purpose of this study is to investigate empirically the relationship between inflation rate and stock market return in Korean stock market. After the literature was reviewed, two regression models were tested for two periods, 1976-1980 and 1981-1986. The results show that there exists strong negative relation between two variables in the higher inflation period, on the contrary unsignificant positive relation in the lower inflation period. The major feature of this study is the use of Box-Jenkins' ARIMA fitted values as measures of expected inflation rates. But this study has many limitations and weaknesses from the view of theory building and research methodology, thus some directions of study are suggested.

담도에 국한되어 증상을 유발한 석회쓸개즙 2 예

윤성우,이지영,하경호,이수경,한나,배효근,박선자 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.2

Limy bile is a rare condition characterized by excessive precipitation of calcium carbonate in the gallbladder or bile duct. Recently we experienced two cases with obstructive jaundice in which limy bile in the common bile duct but not in the gallbladder for one case, and in the common bile duct and intra hepatic duct but not in the gallbladder for another case. The patients were treated by endoscopic sphincterotomy. Here, we report the cases and review the literature.