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)

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.

P168 : Split-face comparison study of new hyaluronic acid filler for efficacy and safety of HA-IDF versus Restylane® for correction of nasolabial folds

( Jie Hyun Jeon ),( Joo Ha Kim ),( Jung Woo Lee ),( Kui Young Park ),( Seong Jun Seo ),( Hae Jun Song ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: After successive trials and failures of various injectable materials such as bovine collagen, polyacryamide, calcium hydroxylapatite, etc., hyaluronic acid (HA) has become the most popular filling material. Many new HA fillers are being produced for the purpose of correcting wrinkles and augmentation of soft tissue. Objectives: This study aimed to test the efficacy, tolerability, and safety of a new HA filler, HA-IDF (Yvoire Classic s touch-up, LG Life Sciences, Inc., Seoul, South Korea) and compare HA-IDF with Restylane (Q-Med, Uppsala, Sweden). Methods: Fifty-eight subjects with visible nasolabial folds (NLFs) were enrolled in a randomized, multi-center, single-blind, active-controlled, matched-pair clinical study. Each subject was injected with HA-IDF in one NLF and Restylane in the other. All participants were assessed for cosmetic change at 2, 10, 18, and 26 weeks. Results: At screening, the average Wrinkle Severity Rating Scale (WSRS) for both right and left NLFs was 3.24±0.43. After 26 weeks, the results were 2.56±0.09 for both groups. There was no significant difference in WSRS scores for wrinkle improvement and in incidence of adverse events for both HA filler treatments. Conclusion: The new HA filler HA-IDF is effective and safe for correcting NLFs.

논문 : 강원도 양양지역 소나무림의 지상부 바이오매스와 수관층 연료특성에 관한 연구

김성용 ( Sung Yong Kim ),이영진 ( Young Jin Lee ),장미나 ( Mi Na Jang ),서연옥 ( Yeon Ok Seo ),구교상 ( Kyo Sang Koo ),정성철 ( Sung Cheol Jung ),김경하 ( Kyung Ha Kim ) 한국임학회 2012 한국산림과학회지 Vol.101 No.2

본 연구의 목적은 강원도 양양지역에 분포하는 소나무림을 대상으로 지상부 바이오매스와 수관층 연료특성에 대하여 분석하고자 하였다. 연구대상지는 강원도 양양군 현남면 하월천리 일대 소나무림으로 선정하였으며, 총 13본의 표본목을 벌채하여 분석하였다. 본 연구 결과에 의하면, 양양지역 소나무림의 줄기밀도(g·cm-3)는 0.347~0.409, 지상부 바이오매스 확장계수는 1.251~1.419의 범위로 나타났다. 지상부 연료량은 총 161.6 Mg·ha-1로 나타났으며, 줄기 126.4 Mg·ha-1, 가지 29.3 Mg·ha-1, 잎 5.9 Mg·ha-1로 나타났다. 수관층 연료특성 인자에 관한 연구에서는 수관화 확산 시 연소될 수 있는 연소가능 연료(잎~1 cm이하 가지)의 비율은 45.2%로 나타났고, 연료량을 수관체적으로 나눈 연소가능 연료밀도(kg·m-3)는 평균 0.178로 나타났다. 본 연구의 결과는 소나무림의 바이오매스 및 탄소 흡수량 추정과 수관화 위험성을 연료적 관점에서 평가하는데 있어 유용한 기초자료가 될 것으로 사료된다. The objective of this study was to analyze the above-ground biomass and crown fuel characteristics of Pinus densiflora stands in Yangyang, Gangwon province. A total of thirteen representative trees were destructively sampled in Yangyang region. The results showed that the stem density (g·cm-3) was 0.347~0.409, whereas the above-ground biomass expansion factors ranged from 1.251~1.419. In terms of crown fuel biomass, the above-ground biomass was 161.6 Mg·ha-1 while the stem biomass, branch biomass and needle biomass were 126.4 Mg·ha-1, 29.3 Mg·ha-1 and 5.9 Mg·ha-1, respectively. Needles and twigs with less than 1 cm diameter accounted 45.2% of the total crown fuel load. The available crown bulk density, which was calculated by dividing the crown fuel load to the crown volume, was 0.178 kg·m-3. The results of this study on the biomass and carbon stocks estimation of the Pinus densiflora together with the crown fire hazard assessment based on crown fuel loads are very significant information for the forest managers.

Comparison of trophic factors changes in the hippocampal CA1 region between the young and adult gerbil induced by transient cerebral ischemia.

Yan, Bing Chun,Park, Joon Ha,Kim, Sung Koo,Choi, Jung Hoon,Lee, Choong Hyun,Yoo, Ki-Yeon,Kwon, Young-Geun,Kim, Young-Myeong,Kim, Jong-Dai,Won, Moo-Ho Kluwer Academic/Plenum Publishers 2012 Cellular and molecular neurobiology Vol.32 No.8

<P>In the present study, we investigated neuronal death/damage in the gerbil hippocampal CA1 region (CA1) and compared changes in some trophic factors, such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), in the CA1 between the adult and young gerbils after 5 min of transient cerebral ischemia. Most of pyramidal neurons (89%) were damaged 4 days after ischemia-reperfusion (I-R) in the adult; however, in the young, about 59% of pyramidal neurons were damaged 7 days after I-R. The immunoreactivity and levels of BDNF and VEGF, not GDNF, in the CA1 of the normal young were lower than those in the normal adult. Four days after I-R in the adult group, the immunoreactivity and levels of BDNF and VEGF were distinctively decreased, and the immunoreactivity and level of GDNF were increased. However, in the young group, all of their immunoreactivities and levels were much higher than those in the normal young group. From 7 days after I-R, all the immunoreactivities and levels were apparently decreased compared to those of the normal adult and young. In brief, we confirmed our recent finding: more delayed and less neuronal death occurred in the young following I-R, and we newly found that the immunoreactivities of trophic factors, such as BDNF, GDNF, and VEGF, in the stratum pyramidale of the CA1 in the young gerbil were much higher than those in the adult gerbil 4 days after transient cerebral ischemia.</P>

Valuation of ecosystem services in the organic carbon of the Pinus densiflora forest at Mt. Namsan, Seoul Metropolitan City

Lee, Eung-Pill,Lee, Soo-In,Jeong, Heon-Mo,Han, Young-Sub,Lee, Seung-Yeon,Park, Jae-Hoon,Jang, Rae-Ha,Hong, Youg-Sik,Jung, Young-Ho,Kim, Eui-Joo,Lee, Sang-Hun,You, Young-Han The Ecological Society of Korea 2019 Journal of Ecology and Environment Vol.43 No.4

Background: Standing biomass, litter production, rate of litter decomposition, amount of litter on forest floor, and amount of soil organic carbon distribution were investigated from March 2016 to November 2018 in order to evaluate the ecosystem value through organic carbon distribution in the Pinus densiflora forest at Namsan, Seoul Metropolitan City. Results: The amount of organic carbon in the Pinus densiflora forest was 261.09 ton C ha^-1 during the research period, and fixed organic carbon in plant through net photosynthesis was 3.2 ton C ha^-1 year^-1. The organic carbon in plant was 62.77 ton C ha^-1 (24.04%), in litter on the forest floor was 3.65 ton C ha^-1 (1.40%), and in soil was 194.67 ton C ha^-1 (74.56%). The value of plant, litter on forest floor, and soil organic carbon distribution were each 6,277,000 won ha^-1, 365, 000 won ha^-1, and 19,467,000 won ha^-1. The value per ton of fixed organic carbon in plant through net photosynthesis was 320,000 won ha^-1 year^-1 and the value of ecosystem services stored in carbon in the Namsan forest ecosystem was about 26.1 million won ha^-1 for 3 years. Conclusions: The results of this study suggest that the pine forests of Namsan rapidly decompose leaves due to the high atmospheric temperature and accumulate a large amount of organic carbon in the soil to provide climate control regulatory service function.

대학생의 건강증진 프로그램 참여의사에 영향을 미치는 주요 요인에 관한 연구

김영복,하은희,김주영,윤영옥 韓國保健敎育.健康增進學會 2001 보건교육건강증진학회지 Vol.18 No.1

This study purposed to examine the participative intention for health promotion program in a university and to find out the factors to associate with the participative intention. The data were based on the self-reported questionnaires from 746 women who study in E university, and this survey performed May, 1998. This study performed to analyze the participative intention for health promotion programs and the factors associate with health promotion program using x2-test and trend test by the PC-SAS 6.12. The major findings were as fellows: 1. The tendency of participative intention for health promotion programs showed that Influenza preventive program was the highest among the health promotion programs, and the next were Weight control program, Rubella preventive program, Fitness program. On the other hand, Smoking preventive program and Non-drinking program were lower than the other program. 2. The four significant factors on participative intention for health promotion programs were grade, concern for health, and behavior change experience through the health education. On the other hand, the cognitive level for health, experience for health education were not the significant factors associate with the participative intention for health promotion programs. 3. The relationship between factors and each health promotion program showedthat Rubella preventive program, Influenza preventive program, Weight control program, Smoking cessation program and Non-drinking program were associated with the grade or the health concern. And Chronic diseases preventive program was associated with the grade and the concern for health. Fitness program and Sex education program were associated with the concern for health and the behavior change experience through health education.

참당귀의 흰쥐 4-Vessel Occlusion 전뇌허혈에 대한 신경방어효과

김영옥,하니나,부영민,박선영,박주영,유영법,신준식,안덕균,김호철 대한본초학회 2002 大韓本草學會誌 Vol.17 No.2

Objectives : Angelicae Radix, the root of Angelica gigas N_AKAI (Umbelliferae) , which has been used to nourish the blood(補血), regulate menstruation(調經), relieve pain and promote bowel movements(崩漏) and activate blood circulation for the treatment of fatigue, headache, constipation and blood troubles in traditional Korean medicine. It's flavour and channel tropism is sweet(甘), pungent(辛), warm(溫), acting on the lung, heart and spleen(肺, 心, 脾). The purpose of study we report here was to determine the neuroprotective effect of Angelica gigas on global ischemia induced by 4-vessel occlusion in Wistar rats. Methods : Angelica gigas extracts was lyphilized after extraction with 85% methanol. We induced 4-VO for 10 minutes and reperfused again. The number of CA1 pyramidal neurons were counted after 7 days of reperfusion under the cresyl violet staining. Results : The results showed that Angelica gigas had significantly neuroprotective effects (100, 250 and 500mg/kg of AR extracts, p<0.001) compared with control group. Each neuroprotective ratio was about 66.1, 79.3 and 78.6% respectively. Immunohistochemical data partially explained the protective effects of Angelica gigas via attenuation of COX-2 induction in hippocampus. Conclusion : Angelica gigas gas neuroprotective effects on the global ischemia induced by 4-vessel occlusion in Wistar rats and the attenuation of COX-2 induction is thought to be its possible mechanism.

후두 미세 수술전후의 음성기능분석

김영모,조정일,김철호,김영진,하현령 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.9