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.

Bloodstream Infections and Clinical Significance of Healthcare-associated Bacteremia: A Multicenter Surveillance Study in Korean Hospitals

Son, Jun Seong,Song, Jae-Hoon,Ko, Kwan Soo,Yeom, Joon Sup,Ki, Hyun Kyun,Kim, Shin-Woo,Chang, Hyun-Ha,Ryu, Seong Yeol,Kim, Yeon-Sook,Jung, Sook-In,Shin, Sang Yop,Oh, Hee Bok,Lee, Yeong Seon,Chung, Doo The Korean Academy of Medical Sciences 2010 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.25 No.7

<P>Recent changes in healthcare systems have changed the epidemiologic paradigms in many infectious fields including bloodstream infection (BSI). We compared clinical characteristics of community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA) BSI. We performed a prospective nationwide multicenter surveillance study from 9 university hospitals in Korea. Total 1,605 blood isolates were collected from 2006 to 2007, and 1,144 isolates were considered true pathogens. HA-BSI accounted for 48.8%, CA-BSI for 33.2%, and HCA-BSI for 18.0%. HA-BSI and HCA-BSI were more likely to have severe comorbidities. <I>Escherichia coli</I> was the most common isolate in CA-BSI (47.1%) and HCA-BSI (27.2%). In contrast, <I>Staphylococcus aureus</I> (15.2%), coagulase-negative <I>Staphylococcus</I> (15.1%) were the common isolates in HA-BSI. The rate of appropriate empiric antimicrobial therapy was the highest in CA-BSI (89.0%) followed by HCA-BSI (76.4%), and HA-BSI (75.0%). The 30-day mortality rate was the highest in HA-BSI (23.0%) followed by HCA-BSI (18.4%), and CA-BSI (10.2%). High Pitt score and inappropriate empirical antibiotic therapy were the independent risk factors for mortality by multivariate analysis. In conclusion, the present data suggest that clinical features, outcome, and microbiologic features of causative pathogens vary by origin of BSI. Especially, HCA-BSI shows unique clinical characteristics, which should be considered a distinct category for more appropriate antibiotic treatment.</P>

Interaction between Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Recent Negative Stressor in Harm Avoidance

Kim, Seog Ju,Cho, Seong-Jin,Jang, Ha Min,Shin, Jonghan,Park, Pil-Whan,Lee, Yu Jin,Cho, In Hee,Choi, Jung-Eun,Lee, Heon-Jeong S. Karger AG 2009 Neuropsychobiology Vol.61 No.1

<P>There have been controversial results regarding the association between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and anxiety-related traits such as harm avoidance (HA). We aimed to investigate the interaction between <I>BDNF</I> Val66Met polymorphism and negative life stressors in HA. <I>BDNF</I> Val66Met polymorphism was genotyped in 391 community-dwelling Koreans (152 males, 239 females; 43.2 ± 14.1 years old). The Temperament and Character Inventory (TCI) and the Center for Epidemiological Studies for Depression Scale (CES-D) were self applied. The Structured Clinical Interview for DSM-IV axis I disorders and face-to-face interviews investigating negative life stressors within the last 6 months were also performed. There was no significant difference in TCI score, major depressive disorder prevalence and CES-D score among the 3 genotypes (94 Met/Met, 188 Val/Met and 109 Val/Val subjects). There was no significant difference in TCI scores between subjects with stressors and those without stressors, while more common major depressive episodes (p = 0.03) and higher CES-D scores (p < 0.001) were found in subjects with stressors. However, there was a significant interaction between the <I>BDNF</I> genotype and negative life stressors in HA (p = 0.02). Only subjects with the Val/Val genotype showed higher HA with recent negative stressors. Our finding suggests that <I>BDNF</I> Val66Met polymorphism might influence HA by interacting with recent negative stress experience.</P><P>Copyright © 2009 S. Karger AG, Basel</P>

Hemochromatosis의 1예

신기영,양영선,최하진,홍숙희 인제대학교 1982 仁濟醫學 Vol.3 No.3

Hemochromatosis는 간 경변증 피부 색소 침착 당뇨병 심부전을 주 증상으로 나타나는 질환인데 본 교실에서는 본증 1예를 경험하고 문헌 고찰과 함께 보고하는 바이다. We have seen a patient with hemochromatosis, who has been clinically studied. A 73 year old man, who had been a heavy alcohol drinker since young, was admitted to our hospital with complaints of right upper abdominal pain, dyspnea, general weakness and fatigue. The typical bronze coloration of skin, liver and skin involvements with iron deposition were demonstrated. The serum iron and total iron binding capacity were elevated up to 187ng/dl and 216ng/dl respectively. Urinary iron excretion was 60.42ug per 24hrs.

外來患者 및 돼지에서의 間接Latex凝集反應法에 依한 Toxoplasma 抗體價 調査硏究

심희숙,나영언,이영하,신대환 충남대학교 의과대학 지역사회의학연구소 1991 충남의대잡지 Vol.18 No.2

This study was undertaken to konw the sero-epidemiologic meanings of toxoplasmosis by Indirect Latex Agglutination test of 514 general outpatients and 100 pigs. The results were obtained as follows: 1. Toxoplasma antibody titers were showed as 418 negative cases(81.3%), 63 cases(12.2%) in a titer of 1:16, 20 cases(3.9%) in a titer of 1:32, 8 cases(1.6%) in a titer of 1:64, 3 cases(0.6% ) in a titer of 1:128 and 2 cases(0.4%) in a titer of 1:256, respectively. 2. Antibody titer was somewhat declined to the nineteen ages (from 6.1% to 3,0%) but was increased from twenty to fifty-nine ages(from 9.1% to 24.2%). The positive percentage of Toxoplasma antibody titers were the highest as 24.2% in the fifties group. Totally, 33 cases(6.5%) among 514 patients was showed as positive reaction. 3. According to the sex group, 16 cases of the male and 17 cases of the female were showed as positive reaction 5.6%, 7.5%, respectively. Positive rates of the female was somewhat higher than that of the male. 4. Antibody titers of sera of the pig were shown as 65 negative cases(65%), 24 cases in a titer of 1:16(24%), 6 casesin 1:32(6%), 3 cases in 1:64(3%) and 2 cases in 1:1.28(2%), respectively . Totally, positive rates was 11%.

비글개에서 신원방우황청심원의 급성 및 아급성독성시험

성하정,권오경,방명주,곽형일,이진영,신대희,박대규,정규혁,윤효인,조명행 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

Single and 4 weeks oral administration of New wonbangwoohwangchungsimwon (NSCH) which was used l-muscone as substitutive material of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs (3 males and 3 females) in acute experiments were administered orally with sinlge dose of 2,000 ㎎/㎏ and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NSCH, 160 ㎎/㎏/day (low dosage group), 400 ㎎/㎏/day (middle dosage group), 1,000 ㎎/㎏/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Administration (1996. 4. 16). LD_50 value for beagle dogs was more than 2,000 ㎎/㎏ per oral for both male and females. In animals administered with NSCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NSCH in beagle dogs is considered to be safe.

Interferon-gamma 투여에 의한 Toxoplasma 감염 마우스의 면역학적 변화

이영하,신대환,심희숙 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.1

This study was performed to evaluate differences of immune responses according to the injection period of recombinant mouse interferon-γ(IFN-γ) in acute murine toxoplasmosis. Each mouse was infected intraperitoneally with 100 cysts of Beverley strain of T. gondii, and injected with 5 × 10 ^4 units of IFN-γ every other day for a total of two injections. From the 1st week after infection, blastogenic responses of splenocytes to concanavalin A(Con. A, 2.5㎍/ml) and Toxoplasma antigen(30.0㎍/ml) were examined at 1 week interval for 4 weeks. Also serum IgG and IgM antibody titers were examined by enzyme-linked immunosorbent assay, and immunohistochemical study of brain tissues were done at the same time. Toxoplasma antigen-treated blastogenic responses were significantly increased in the IFN-γ injected groups as compared with Toxoplasma-infected group. However Con. A-treated blastogenic responses were increased in the mice that received two doses of IFN-γ on day 4 and 2 before infection, or day 2 and 0 before infection. The serum IgG and IgM antibody titers of IFN-γ injected groups were increased from 2 weeks after infection, and IgM antibody titers were increased at 2 and 3 weeks after infection as compared with non-infected group. No significant differences were revealed between IFN-γ injected groups and Toxoplasma-infected group. T gondii was found as tachyzoites at 2 weeks after infection, and cysts found in 4 weeks. However, no T. gondii was detected in IFN-γ injected groups in the same period. The results suggested that IFN-γ administration to T. gondii-infected mice improve the cell-mediated immune responses, especially when IFN-γ was injected just before T. gondii infection. But there was not significant differences serum antibody titers and immunohistochemical findings of brain tissues according to the injection period of IFN-γ.

고등어부시의 제조에 관한 연구 : 1. 제조중의 정미성분의 변화

고신효,임희유,고용구,하진환 濟州大學校 工科大學 産業技術硏究所 1993 産業技術硏究報告 Vol.4 No.-

Mackerel-bushi was manufactured as a natural flavoring substance and in each processing step the taste compounds including nucleotides and their related copmounds. free amino acids, non-volatile organic acids, trimethylamine oxide, trimethylamhe and betaine were determined. IMP and inosine were abundant in Mackerel-bushi which marked 465.3㎎/l00g and 465.7㎎/l00g on dry basis while ADP was trace in content. 17 species of free amino acids were isolated and identified from the extracts of raw material and its products. The abun-dant amino acids in the extracts were lysine, taurine, phenylalanine and alanine, and those were consisted of 65.8~80.7% of the total free amino acids while isoleucine, aspartic acid, tyrosine and leucine were poor, and glycine was trace in content. Citric and lactic acids were 95% of total nonvolatile organic acids, and malonic, oxalic and α-ketoglutaric acids were poor. The content of TMAO and TMA in the extract of Mackerel-bushi were 11.9㎎/l0g and 13.5㎎/100g on dry basis and that of betaine was 93.1㎎/100g. The major minerals were Ca. Na. K. and Mg.

VRE 감염증의 임상상, 미생물학적 특성 분석 및 유전적 관련성 비교 : 전국 6개 병원에서 분리된 VRE를 중심으로

정희진,박정원,엄중식,하경임,신종희,김정미,이혜수,박영희,김우주,박승철 대한감염학회 2002 감염 Vol.34 No.5

금강유역 수질오염 실태조사

최신석,오희목,강명규,조통래,이규승,유종국,이영하 忠南大學校 環境問題硏究所 1988 環境硏究 Vol.6 No.1

조사 구역 상류 지점의 평균 수질은 pH가 7.1, DO가 8.3mg/ℓ, BOD가 1.7mg/ℓ, COD가 1.7mg/ℓ, SS가 15.4mg/ℓ, 분변성 대장균이 1.1x10³ MPN/100ml고 상수원 수 1급 내지 2급의 양호한 상태이고 하류지점의 수질은 pH가 6.8, DO가 7.7mg/ℓ, BOD가 2.2mg/ℓ, COD가 2.4mg/ℓ, 분변성 대장균이 1.7x10³MPN/100ml로 상수원 수 2급 내지 3급의 상태를 나타내 하류로 내려가면서 오염도가 증가하는 것으로 나타났다. 청주시의 영향을 크게 받는 미호천 하류의 평균수질은 pH가 7.2, DO가 6.3mg/ℓ, BOD가 16.2mg/ℓ, COD가 15.1mg/ℓ, 분변성 대장균이 1.6x10??MPN/100ml로 심각한 오염 상태를 보여 청주시와 대전시가 금강 본류의 주 수질 오염원으로 나타났다. 영양 염류 (NH₃-N, NO₂-N, NO₃-N, PO₄-P)와 무기성 유해 성분 (Cl-, CN-, F-)의 함량은 지천의 일부 지점을 제외하고는 극히 낮은 수준으로 검출되었으며, 유기인, 페놀류, PCB 성분은 조사기간 중 전혀 검출되지 않았다. 또한 Fe, Zn, Cu, Mn, Cr, Pb, Cd, Hg등의 중금속은 검출되지 않거나 하천 수질 기준 또는 식용수 수질 기준의 허용치를 초과하지 않는 양호한 수준으로 나타났다.