Preparation of Thermo-Responsive and Injectable Hydrogels Based on Hyaluronic Acid and Poly(N-isopropylacrylamide) and Their Drug Release Behaviors

Ha Dong In,Lee Sang Bong,Chong Moo Sang,Lee Young Moo,Kim So Yeon,Park Young Hoon The Polymer Society of Korea 2006 Macromolecular Research Vol.14 No.1

Copolymers composed of hyaluronic acid (HA) and poly(N-isopropylacrylamide) (PNIPAAm) were prepared to create temperature-sensitive injectable gels for use in controlled drug delivery applications. Semi-telechelic PNIPAAm, with amino groups at the end of each main chain, was synthesized by radical polymerization using 2-aminoethanethiol hydrochloride (AESH) as the chain transfer agent, and was then grafted onto the carboxyl groups of HA using carbodiimide chemistry. The result of the thermo-optical analysis revealed that the phase transition of the PNIPAAm-grafted HA solution occurred at around 30$\∼$33$^{circ}C$. As the graft yield of PNIPAAm onto the HA backbone increased, the HA-g-PNIPAAm copolymer solution exhibited sharper phase transition. The short chain PNIPAAm-grafted HA ($M_{w}$=6,100) showed a narrower temperature range for optical turbidity changes than the long chain PNIPAAm-grafted HA ($M_{w}$=13,100). PNIPAAm-grafted HA exhibited an increase in viscosity above 35$^{circ}C$, thus allowing the gels to maintain their shape for 24 h after in vivo administration. From the in vitro riboflavin release study, the HA-g-PNIPAAm gel showed a more sustained release behavior when the grafting yield of PNIPAAm onto the HA backbone was increased. In addition, BSA released from the PNIPAAm-g-HA gels showed a maximum concentration in the blood 12 h after being injected into the dorsal surface of a rabbit, followed by a sustained release profile after 60 h.

연구논문 : 만성 바이러스간질환에서 간섬유화의 다양한 비침습 혈청표지자검사의 비교

김선민 ( Sun Min Kim ),손주현 ( Joo Hyun Sohn ),김태엽 ( Tae Yeob Kim ),노영욱 ( Young Wook Roh ),은창수 ( Chang Soo Eun ),전용철 ( Yong Cheol Jeon ),한동수 ( Dong Soo Han ),오영하 ( Young Ha Oh ) 대한간학회 2009 Clinical and Molecular Hepatology(대한간학회지) Vol.15 No.4

목적: 만성 바이러스간질환에서 병의 경과와 예후를 평가하고 치료반응을 예측함에 있어 간섬유화의 진단은 중요하다. 최근 간섬유화 평가에 표준방법이지만 침습적 간생검을 대신하여 여러 가지 비침습적 진단법이 이용되고 있고, 또한 새로운 검사법들이 개발되고 있다. 저자들은 만성 B형 및 C형간염 환자를 대상으로 임상에서 광범위하게 흔히 시행하는 혈액검사와 임상 소견을 이용한 아래와 같은 진단법들만으로 간섬유화를 얼마나 정확하게 평가할 수 있는지 알아보고, 단일 검사로 간섬유화를 평가하는 데 유용하다고 알려져 있는 hyaluronic acid(HA)와 IV형 콜라겐 농도와 비교하여 그 임상적 유용성을 평가하였다. 대상과 방법: 2002년 3월부터 2007년 2월까지 만성 바이러스간 질환으로 간생검을 시행받은 225명의 환자(HBV 180명, HCV 43명, HBV+HCV 2명)를 대상으로 분석하였다. 간생검을 시행하는 날에 말초혈액검사, 혈액응고검사, 혈청생화학검사를 시행하고, 혈중 HA, IV형 콜라겐 농도를 측정하였다. 간섬유화의 정도는 F0(섬유화가 없음), F1(문맥역 섬유화), F2(문맥주변부 섬유화), F3(섬유성 격막) 및 F4(간경변증)의 4단계로 구분하였다. 대상 환자를 F0-1, F2-4 혹은 F0-2, F3-4의 두 집단으로 분류하여 두 집단을 구분하고자 할 때 AAR(AST/ALT ratio), API(age-platelet index), APRI(AST to platelet index), CDS(cirrhosis discriminant score), platelet count, HA, IV형 콜라겐의 예측능을 area under the receiver operating characteristic curve (AUROC)값을 이용하여 비교하였다. 결과: 대상환자의 섬유화의 단계는 F0 집단은 17명, F1 집단은 40명, F2 집단은 61명, F3 집단은 74명, F4 집단은 33명이었다. 의미 있는 간섬유화를 F2 이상으로 판단할 때, 의미 있는 섬유화의 예측에 대한 AUROC 값은 APRI=0.822, CDS=0.776, platelet count=0.773, API=0.756, HA=0.749, IV형 콜라겐=0.718, AAR=0.642 순이었고, F3 이상의 광범위한 섬유화 예측에 대한 AUROC값은 CDS=0.835, platelet count=0.795, API=0.794, HA=0.766, AAR=0.711, IV형 콜라겐=0.697, APRI=0.691 순으로 관찰되었다. 결론: 만성 바이러스간질환에서 간섬유화를 평가하는 데 임상 소견 및 혈액검사를 이용한 방법들이 비침습적 진단법 중 단독 검사로도 유용한 것으로 알려져 있는 혈중 HA와 IV형 콜라겐 농도와 비교하여 우월하거나 대등하였다. 특히 APRI는 다른 인자들에 비해 F2 이상의 의미 있는 섬유화를 예측하는 데 가장 유용하였고, CDS는 F3 이상의 광범위한 섬유화를 예측하는 데 가장 유용하였다. Background/Aims: The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. Methods: We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. Results: There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (≥F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (≥F3). Conclusions: Conclusions: All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis. (Korean J Hepatol 2009;15:454-463)

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

HAZARD ANALYSIS USING MULTI-COMPONENT ANALYSIS IN CHEMICAL PROCESSES

Kim,Ku-Hwoi,Lee,Dong-Eon n,Kim,Yonhg-Ha,Yoon,En-Sup 한국화재소방학회 2001 한국화재소방학회 학술대회 논문집 Vol.2001 No.추계

신경섬유종증-제 2형의 진단과 치료 : 16례의 임상경험 Experience of 16 Cases

김정은,백선하,김종수,이상형,오창완,김동규,정희원,김현집,조병규,한대희,최길수 대한신경외과학회 1996 Journal of Korean neurosurgical society Vol.25 No.12

Neurofibromatosis type 2(NF-2) is a dominantly inherited disorder characterized by the occurrence of bilateral acoustic neurinomas and the frequent association of other central nervous system tumors. We present a retrospective review of 16 patients with NF-2 who were treated at our hospital from 1984 to 1995 in 13 cases, the diagnoses of Nf-2 were based on the criteria developed at the Consensus Development Conference of National Institute of Health in the United States, and in another 3 cases. the criterias of NF-2 were not fully satisfied, but the diagnoses of NF-2 were highly suspected. The average age of the patients was 27.6 years, ranging from 13 years to 56 years. The most common symptom was hearing difficulty : intervals between symptom onset and deafness ranged from 8 months to 6 years(mean : 2.9 years) One family of NF-2 was documented consisting of a sister a brother and their mother. Nine patients underwent operations on unilateral acoustic neurinomas : these were subtotally removed in eight patients and totally in one patient Among these patients five were deaf on the ipsilateral side at surgery. Among the other four patients with useful hearing before surgery, hearing was preserved to preoperative status in two patients. Four patients with diagnoses of meningioma, received operations to relieve mass effect with subtotal removal in two patients and total removal in the other two. Early diagnosis and treatment are the most important in the management planning of patients with NF-2 for reasons of early manifestation and rapid progression of the disease.

Matched Comparison of Fusion Rates between Hydroxyapatite Demineralized Bone Matrix and Autograft in Lumbar Interbody Fusion

Kim, Dae Hwan,Lee, Nam,Shin, Dong Ah,Yi, Seong,Kim, Keung Nyun,Ha, Yoon The Korean Neurosurgical Society 2016 Journal of Korean neurosurgical society Vol.59 No.4

Objective : To compare the fusion rate of a hydroxyapatite demineralized bone matrix (DBM) with post-laminectomy acquired autograft in lumbar interbody fusion surgery and to evaluate the correlation between fusion rate and clinical outcome. Methods : From January 2013 to April 2014, 98 patients underwent lumbar interbody fusion surgery with hydroxyapatite DBM (HA-DBM group) in our institute. Of those patients, 65 received complete CT scans for 12 months postoperatively in order to evaluate fusion status. For comparison with autograft, we selected another 65 patients who underwent lumbar interbody fusion surgery with post-laminectomy acquired autograft (Autograft group) during the same period. Both fusion material groups were matched in terms of age, sex, body mass index (BMI), and bone mineral density (BMD). To evaluate the clinical outcomes, we analyzed the results of visual analogue scale (VAS), Oswestry Disability Index (ODI), and Short Form Health Survey (SF-36). Results : We reviewed the CT scans of 149 fusion levels in 130 patients (HA-DBM group, 75 levels/65 patients; Autograft group, 74 levels/65 patients). Age, sex, BMI, and BMD were not significantly different between the groups (p=0.528, p=0.848, p=0.527, and p=0.610, respectively). The HA-DBM group showed 39 of 75 fused levels (52%), and the Autograft group showed 46 of 74 fused levels (62.2%). This difference was not statistically significant (p=0.21). In the HA-DBM group, older age and low BMD were significantly associated with non-fusion (61.24 vs. 66.68, p=0.027; -1.63 vs. -2.29, p=0.015, respectively). VAS and ODI showed significant improvement after surgery when fusion was successfully achieved in both groups (p=0.004, p=0.002, HA-DBM group; p=0.012, p=0.03, Autograft group). Conclusion : The fusion rates of the hydroxyapatite DBM and Autograft groups were not significantly different. In addition, clinical outcomes were similar between the groups. However, older age and low BMD are risk factors that might induce non-union after surgery with hydroxyapatite DBM.

몬순기후와 복잡지형의 특성을 갖는 광릉 산림유역의 물과 탄소순환에 대한 교차규모 연구로부터의 교훈

이동호 ( Dong Ho Lee ),김준 ( Joon Kim ),김수진 ( Su Jin Kim ),문상기 ( Sang Ki Moon ),이재석 ( Jae Seok Lee ),임종환 ( Jong Hwan Lim ),손요환 ( Yo Whan Son ),강신규 ( Sin Kyu Kang ),김상현 ( Sang Hyun Kim ),김경하 ( Kyong Ha Kim 한국농림기상학회 2007 한국농림기상학회지 Vol.9 No.2

광릉 슈퍼사이트에서 대기와 식생간의 에너지와 물질교환 규명은 지형과 식생의 복잡성으로 인해 많은 기술적인 어려움에 직면하고 있다. 따라서 KoFlux 연구에서는 상호보완적인 다중 분야의 연구를 통해 이러한 어려움을 극복하기 위한 시도를 해 오고 있다. 본 논문에서는 현재 진행중인 KoFlux 연구의 예비결과 중 특히 광릉사이트에서의 물/탄소수지, 물과 탄소순환의 상호관련성 그리고 몬순기후하의 생태계에서 탄소순환에 미치는 수문학적 요인의 중요성에 대해 중점적으로 논의하고자 한다. 광릉낙엽활엽수림의 순생태생산량 (NEP)은 광범위한 생태학적 연구결과에 따르면 약 ~2.6 t C/ha/y로 예상된다. 이를 미기상 플럭스 관측 결과와 함께 고려할 때 광릉 산림은 탄소의 중요한 육상흡원으로서 기능함을 예상할 수 있다. 다양한 생태수문 관측에 의해 규명된 유역단위 물수지에 의하면 연단위 전체강수량의 약 30-40%가 증발산 (ET)에 해당함을 나타내고 있다. 광릉산림의 대표적인 수종인 졸참과 서어나무의 잎에서 얻어진 탄소 안정동위 원소 조성에 근거하여 계산된 식물 성장기간의 평균 물 이용효율(WUE)은 약 ~12 μmol CO2/mmol H2O에 해당된다. 얻어진 증발산량과 물이용효율은 유역단위의 생태계 생산량을 산출하는데 이용될 수 있다. 나이테 성장량과 토양호흡량의 연단위 변화는 강수량과 강수의 패턴에 의해 크게 영향을 받음을 보이고, 이는 몬순기후에 영향을 받는 동아시아 지역 생태계에서 탄소 순환과정이 수문학적 조건과 밀접한 상관관계를 가짐을 지시한다. 연구지역의 공간적 특성을 정량화하기 위해 관측지의 구조 및 기능적 단위를 규명하기 위한 연구가 진행되고 있고 이를 통해 서로 다른 시공간 규모에서 진행되고 있는 연구의 결과물을 체계적으로 연결 통합하고 나아가 보다 광역적인 규모에서 대표적인 물/탄소 수지를 산출하기 위한 연구가 시도되고 있다. KoFlux Gwangneung Supersite comprises complex topography and diverse vegetation types (and structures), which necessitate complementary multi-disciplinary measurements to understand energy and matter exchange. Here, we report the results of this ongoing research with special focuses on carbon/water budgets in Gwangneung forest, implications of inter-dependency between water and carbon cycles, and the importance of hydrology in carbon cycling under monsoon climate. Comprehensive biometric and chamber measurements indicated the mean annual net ecosystem productivity (NEP) of this forest to be ~2.6 t C ha-1 y-1. In conjunction with the tower flux measurement, the preliminary carbon budget suggests the Gwangneung forest to be an important sink for atmospheric CO2. The catchment scale water budget indicated that 30~40% of annual precipitation was apportioned to evapotranspiration (ET). The growing season average of the water use efficiency (WUE), determined from leaf carbon isotope ratios of representative tree species, was about 12 μmol CO2/mmol H2O with noticeable seasonal variations. Such information on ET and WUE can be used to constrain the catchment scale carbon uptake. Inter-annual variations in tree ring growth and soil respiration rates correlated with the magnitude and the pattern of precipitation during the growing season, which requires further investigation of the effect of a monsoon climate on the catchment carbon cycle. Additionally, we examine whether structural and functional units exist in this catchment by characterizing the spatial heterogeneity of the study site, which will provide the linkage between different spatial and temporal scale measurements.

말초염증에 의한 등족뿌리신경절의 brain-derived neurotrophic factor 합성의 변화

김상열,김정기,김효신,이상지,하선옥,홍해숙,김동선 대한해부학회 1998 Anatomy & Cell Biology Vol.31 No.3

위선암에서 E-cadherin의 표출양상에 관한 연구

강동하,김대중,김창진,김의한,양승하 순천향의학연구소 2000 Journal of Soonchunhyang Medical Science Vol.6 No.2

Gastric adenocarcinoma is the most common malignant tumor in Korea. Many oncogens have been found in malignant tumor cells. E-cadherin located in cell membrane is important for progression and metastasis of tumor. To evaluate the expression of E-cadherin according to histopathologic features and the relation between E-cadherin and prognosis on gastric adenocarcinoma, we have performed immune staining, using mouse HECD-1 for 97 cases. The results were as follows; 1) Gastric adenocacinoma showed the loss or marked reduction of the expression of E-cadherin in 30.9% of 97 cases, and early carcinoma 34.2% and advanced 28.8%. 2) According to differentiation of gastric adenocarcinoma, cases showing the loss or marked reduction of the expression of E-cadherin was well differentiated form 16.1%, moderately 35.7%, poorly 31.9% and mucinous carcinoma 100%. 3) According to the degree of invasion in early carcinoma, cases showing the loss or marked reduction of the expression of E-cadherin was carcinoma within mucosa 41.2% and carcinoma invaded to submucosa 28.6%, but there is no significant difference according to types. 4) According to absence or presence of lymph node metastasis in advanced carcinoma, cases showing the loss or marked reduction of the expression of E-cadherin was 17.6% in non-metastatic cases and 33.3% in metastatic cases, but there is no significant difference according to degree of invasion. Above results indicated that the loss or marked reduction of the expression of E-cadherin in gastric adenocarcinoma may be related to prognosis of the patients.

Effect of Non-animal-Derived Nitrogen Sources on the Production of Hyaluronic Acid by Streptococcus sp. KL0188

Lee, Gil-Yong,Ha, Suk-Jin,Jung, Jong-Hyun,Seo, Dong-Ho,Park, Jong-Yul,Kim, Su-Rin,Park, Nam-Woo,Kweon, Dong-Keon,Park, Sang-Hoo,Park, Cheon-Seok The Korean Society for Applied Biological Chemistr 2009 Applied Biological Chemistry (Appl Biol Chem) Vol.52 No.3

Hyaluronic acid (HA) is a linear high-molecular-weight polysaccharide with useful biomedical applications. Streptococcus zooepidemicus, a typical HA-producing bacterium, requires an animal-derived nitrogen source such as tryptone, peptone or sheep blood as a nutrient. Sixteen non-animal-derived (NAD) nitrogen sources were tested as a replacement for the expensive animal-derived nitrogen sources, which may have safety issues. Among the sixteen tested NAD nitrogen sources, a yeast-derived nitrogen source (YE 0251) showed the highest HA productivity, which was equivalent to the control HA production medium containing tryptone in a 5-L jar and in 3,000-L industrial fermentations. In the 3,000-L fermentation, YE 0251 increased cell mass (dry cell weight) and HA production by 11% and 8%, respectively, compared with the control HA production medium. The fmal specific volumetric productivity (0.41 g/L h) was improved by about 70% after reducing the fermentation time from 20 h to 12 h, compared to the conventional production medium.