Characterizations of Modified Silica Nanoparticles(I)

Min, Seong-Kee,Park, Chan-Young,Lee, Won-Ki,Seul, Soo-Duk Materials Research Society of Korea 2012 한국재료학회지 Vol.22 No.6

(3-mercaptopropyl)trimethoxysilane (MPTMS) was used as a silylation agent, and modified silica nanoparticles were prepared by solution polymerization. 2.0 g of silica nanoparticles, 150 ml of toluene, and 20 ml of MPTMS were put into a 300 ml flask, and these mixtures were dispersed with ultrasonic vibration for 60 min. 0.2 g of hydroquinone as an inhibitor and 1 to 2 drops of 2,6-dimethylpyridine as a catalyst were added into the mixture. The mixture was then stirred with a magnetic stirrer for 8 hrs. at room temperature. After the reaction, the mixture was centrifuged for 1 hr. at 6000rpm. After precipitation, 150 ml of ethanol was added, and ultrasonic vibration was applied for 30 min. After the ultrasonic vibration, centrifugation was carried out again for 1 hr. at 6000rpm. Organo-modification of silica nanoparticles with a ${\gamma}$-methacryloxypropyl functional group was successfully achieved by solution polymerization in the ethanol solution. The characteristics of the ${\gamma}$-mercaptopropyl modified silica nanoparticles (MPSN) were examined using X-ray photoelectron spectroscopy (XPS, THERMO VG SCIENTIFIC, MultiLab 2000), a laser scattering system (LSS, TOPCON Co., GLS-1000), Fourier transform infrared spectroscopy (FTIR, JASCO INTERNATIONL CO., FT/IR-4200), scanning electron microscopy (SEM, HITACHI, S-2400), an elemental analysis (EA, Elementar, Vario macro/micro) and a thermogravimetric analysis (TGA, Perkin Elmer, TGA 7, Pyris 1). From the analysis results, the content of the methacryloxypropyl group was 0.98 mmol/g and the conversion rate of acrylamide monomer was 93%. SEM analysis results showed that the organo-modification of ultra-fine particles effectively prevented their agglomeration and improved their dispensability.

우울증 환자 치료에 있어서 Tianeptine과 Sertraline의 효과와 안전성 비교

이민수,강성민,기백석,연병길,오병훈,이철,채정민,백인호 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.2

연구목적: 주요 우울증의 치료에 있어서 티아넵틴과 써트랄린의 임상적 효과와 안정성을 비교하기 위하여 연구를 시행하였다. 방법: DSM-IV 진단 기준에 의거하여 주요 우울증의 진단기준에 부합되고 17항목 해밀턴 우울척도 점수가 14점 이상인 환자를 대상으로 하였다. 총 40명의 환자를 무작위적 방식에 따라 티아넵틴 치료군과 써트랄린 치료군으로 분류하였다. 선탠된 환자에서 다른 항우울제를 복용하고 있는 경우 7일 이상의 약물 배설기간을 가진 후 티아넵틴과 써트랄린을 각각 6주간 투여하였으며, 기준점, 1주후, 2주 후, 4주 후, 6주 후에 HAM-D, MADRS, 그리고 CGI, COVI 등을 사용하여 평가하였다. 본 연구기간 중 발생된 모든 부작용은 부작용의 발생 및 소실 시기, 심한 정도, 발생 빈도, 관련 조치 및 결과에 대하여 증례기록서에 기록하도록 하였다. 결과: 30명(티아넵틴군 15명 ; 써트랄린군 15명)이 6주간의 연구를 완결하였고 티아넵틴 치료군에서는 1일 37.5mg을 투여하였으며 써트랄린군에서는 1일 평균 64.0±22.5mg을 투여하였다. 본 연구 결과 HAM-D, MADRS, CGI 상에서 두 군 모두에서 치료 1주 후부터 유의한 감소를 나타내었으며 이는 2주 후, 4주 후, 6주 후에도 지속적인 감소를 보였고 두 군간에 항우울 효과의 차이는 없었다. 활력징후, 일반 혈액학, 생화학, 심전도 검사 등에서는 두 군 모두 유의한 변화는 없었다. 티아넵틴과 관련된 부작용으로 흔히 보고한 증상은 오심(33.3%), 복부 불쾌감(26.7%), 구강 건조(20.0%), 두통(13.3%)등 이었고 써트랄린 치료군에서는 구강 건조(53.3%), 두통(46.7%), 오심(33.3%), 그리고 식욕 부진(33.3%)등으로 티아넵틴군에서 보다 적은 발현빈도를 보였다. 결론: 티아넵틴은 우울증의 치료에 있어서 효과적이고, 내약성이 우수한, 안전한 항우울제이다. Objective: This study was designed to evaluate the efficacy and safety of tianeptine and sertraline in the treatment of patients with depression. Method: The study was done on the patients with major depression diagnosed by DSM-IV, who had aHamilton Rating Scale for Depression(HAM-D) score ≥ 14 on the first 17 items of the HAM-D. A total of 40 patients were randomly assigned to tianeptine group and sertraline group. Tianeptine and sertraline were prescribed to each group. 6 weeks of each medication was carried out after 7 days of drug excretion period. Evaluation using 17 item HAM-D, Montgomery and Åsberg Depression Rating Scale(MADRS), Clinical Global Impression Scale (CGI), and Covi Scale was done on the baseline and after 1 week, 2 weeks, 4 weeks, and 6 weeks. Regrding all side effects that had occurred during the period of our study such as their developed/disappeaed time, severitien, incidences, managements and results have been recorded. Results: A total of 30 patients(tianeptine group 15 ; sertraline froup 15) finished the 6 weeks of research. 37.5mg of the daily dose was regularly prescribed to the tianeptine group, the average amount of 64.0±22.5mg of the final daily dose was prescribed to the sertraline group. Total 17 item HAM-D scores, total points of MADRS and CGI showed significant decrease after 1 week in each treatment froup and continous decrease after 2, 4 and 6 weeks ; and no difference was found between tianeptine group and sertaline group in the antidepressant efficacy. Also there were no significant changes in vital sign, CBC, chemistry, and EKG in each treatment group. The common reported side effects of tianeptine were nausea(33.3%), epigastic distress(26.7%), dry mouth(20.0%), headache(13.3%) and those of sertraline were dry mouth (53.3%), headache(46.7%), nausea(33.3%), anorexia(33.3%). Conclusion: According to the results, tianeptine was effective in improvement of depressive symptoms and was well tolerated and safe in patients with depression.

Comparison of Bradykinin- and Platelet-Derived Growth Factor-Induced Phosphoinositide Turnover in NIH 3T3 Cells

Lee, Kee-Ho,Ryu, Yong-Wun,Yoo, Young-Do,Bai, Dong-Hoon,Yu, Ju-Hyun,Kim, Chang-Min Korean Society for Biochemistry and Molecular Biol 1996 Journal of biochemistry and molecular biology Vol.29 No.6

Phosphoinositide turnover in response to platelet-derived growth factor, epidermal growth factor, and bradykinin was evaluated in NIH 3T3 cells. Platelet-derived growth factor and bradykinin induced a significant increase in incorporation of $^{32}P$ into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4.5-bisphosphate ($PIP_2$) in serum-starved NIH 3T3 cells. However, epidermal growth factor increased incorporation of $^{32}P$ into these phosphoinositides by only a small amount. Stimulation with platelet-derived growth factor, not bradykinin, caused a rapid elevation of PI and PIP kinase activities that were maximally activated within 10 min. The maximal levels of their elevation in cells with plateletderived growth factor stimulation were 3.2-fold for PI kinase, and 2.1-fold for PIP kinase. Short term pretreatment of NIH 3T3 cells with phorbol 12-myristate 13-acetate, activator of protein kinase C. caused an approximately 60% decrease in platelet-derived growth factor-induced PI kinase activities, indicating the feedback regulation of phosphoinositide turnover by protein kinase C. These results suggest that although the enhancement of phosphoinositide turnover is a rapidly occurring response in platelet-derived growth factor- or bradykinin-stimulated NIH 3T3 cells, phosphoinositide kinases may be associated with initial signal transduction pathway relevant to platelet-derived growth factor but not to bradykinin.

Lumbricus rubellus에 존재하는 Lumbrokinase의 Ubiquitin-conjugate 분해활성에 관한 연구

우기민,이상한,조만희 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

본 연구에서 Lumbricus rubellus에 존재하는 강력한 fibrinolytic 효소인 Lumbrokinse들을 여러 크로마토그래피법을 이용하여 부분정제하고 그들의 생화학적 성질들을 조사하고 비교하였다. L. rubellus의 단백질 추출물은 fibrinogen, lactalbumin, BSA, casein 등 다양한 단백질들을 분해하는 활성을 가졌으며, 그들의 활성은 poly-lysine같은 poly-cation들에 의하여 활성화되었다. 또한 이러한 활성화 정도는 poly-cation들의 길이에 의존적이며 poly-lysine의 경우 이성체에 상관없이 모두 활성화시켰다. DEAE-Sepharose를 통하여 확인된 3 종류의 분해활성으로부터 2 종류의 서로 다른 Lumbrokinse들을 Phenyl-Sepharose, Superose-12 크로마토그래피들을 통하여 부분정제하여 E-I, E-III라고 명명하였다. SDS-PAGE와 gel filtration을 시행하였을 때 그들은 각각 33 kD과 38 kDa의 폴리펩타이드로 구성된 단일체로 규명되었다. E-I의 fibrinogen을 분해하는 특이적 활성은 poly-lysine이 없을 경우 3.75 ng hydrolysis/ng enzyme/20 min으로 상대적으로 낮았으나 poly-lysine이 첨가될 경우 75 ng hydrolysis/ng enzyme/20 min로 활성이 20배가량 증가하였다. 반면 E-III는 poly-lysine이 없을 경우 20 ng hydrolysis/ng enzyme/20 min으로 상대적으로 높았지만 poly-lysine의 첨가시 129 ng hydrolysis/ng enzyme/20 min로 약 6.5배의 증가를 보였다. 0.2 M의 KCI은 poly-lysine에 의한 fibrinogen 분해활성을 강하게 억제하였으며 펩타이드 분해활성은 E-I와 E-III가 서로 다른 영향을 받았다. E-III는 poly-lysine에 의해 증가된 활성이 억제받는 반면, E-I는 오히려 펩타이드 분해활성이 KCI에 의하여 10배가량 증가되었다. 이러한 상반된 결과는 두 효소가 서로 다른 분해기작과 조절기작을 가짐을 의미한다. 정제된 E-I와 E-III는 놀랍게도 ubiquitin이 결합된 일련의 단백질들을 분해하였으며, 이 활성도 또한 poly-lysine에 의하여 증가되었다. 또한 ubiquitin-conjugate의 분해활성은 PMSF에 의하여 억제받으므로 serine계의 단백질 분해효소이며 IAA에 의하여 억제받지 않으므로 활성화 부위에 sulfide 기가 관여하지 않는 것으로 판명되었다. 또한 fibrinogen의 분해에서와 같이 이들의 활성도 KCI에 의해 억제되었다. Ubiquitin-conjugate들은 분해된 후 자유 ubiquitin이 반응산물로 나타났으므로 E-I과 E-III는 포유동물들에 존재하는 ubiquitin C-terminal hydrolase (UCH)의 새로운 종류이거나 26S proteasome을 대신할 수 있는 또 다른 형태의 단백질 분해효소일 가능성을 제공해준다.

Simulated Moving Bed를 이용한 Bupivacaine 키랄분리 : (1) Preparative Chromatography를 이용한 기본조건 결정 (1) Optical Separation Conditions for Preparative Chromatography

윤지연,이중기,서성섭,최민호,박태진 한국화학공학회 2003 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.41 No.6

Racemate Bupivacaine의 키랄분리를 위한 크로마토그래피의 최적분리조건을 조사하였다. Kromasii^(�) 키랄고정상에서 최적이동상조성 성분은 n-hexane/2-propanol/acetic acid/triethylamine, 99/1/0.3/0.05(vol.%)이였다. 이동상 조성성분인 2-propanol의 부피비가 증가할수록 체류시간과 분리도가 동시에 감소되었다. 이동상 성분 중에서 미량으로 존재하는 triethylamine이 증가할수록 피크의 sharpness가 증가하고 체류시간 역시 감소하였다. 또한, acetic acid가 없으면, 크로마토그래피 광학분할이 불가능하였으며 부피 0.3%에서 분리도가 가장 높음을 확인할 수 있었다. 한편, 키랄의약품의 대량분리방법중의 하나인 SMB(simulated moving bed)크로마토그래피 시스템(직경 1.0cm×10cm×8개 칼럼으로 구성)의 최적분리조건을 전산모사에 의해 구하였으며, 이를 실험으로 확인하였다. 그 결과 switching time 15분, feed의 유량 0.1 ml/min, desorbent 0.86 ml/min, raffinate 0.3 ml/min, extract 0.66 ml/min, recycle 1.0 ml/min일 때 100% 순도의 R-form과 S-form을 얻을 수 있었으며, 실험치와 전산모사치간의 오차는 ??2%이내였다. The chiral separation of racemate Bupivacaine was carried out to find the optimum condition for chromatographic system. The optimum species and composition for mobile phase were n-hexane/2-propanol/acetic acid/triethylamine, 99/1/0.3/0.05(vol.%) in case Kromasil� chiral stationary phase was employed. The retention time and resolution decreased with the increase in the ratio of 2-propanol in the mobile phase. The sharpness of peak and retention time decreased, as the content of triethylamine increased. Without the existence of acetic acid, the chromatographic separation didn't occur, and the resolution was the highest at the acetic acid volume ratio of 0.3%. The optimum condition of SMB (simulated moving bed) was determined by simulation and its results was compared with exprimental data from lab-scale SMB (10 mm 1D×8 ea). Rased on the SMB simulation and experimental results, 100% purity of R and S Bupivacaine were obtained and the error between the calculated and experimental value was within ±2%.

간질환환자의 위내용물 배출시간에 관한 연구

함준수(Joon Soo Hahm),이동후(Dong Hoo Lee),박경남(Kyung Nam Park),이민호(Min Ho Lee),이종철(Jong Chul Rhee),기춘석(Choon Suck Kee),유대현(Dae Hyun Yoo) 대한소화기학회 1989 대한소화기학회지 Vol.21 No.2

N/A Gastric emptying time(GET) is influenced by several factors, such as neura), hormonal and composi- tion and physiochemical properties of food. The patients with delayed GET have some upper gastrointestinal symptoms such as recurrent nausea, vomiting, postprandia! Bloating, anorexia, and iveight loss. And also, almost of acute hepatitis and a part of chronic ]iver disease patients have similar symptoms of the patients with delayed GET. Therefore We performed GET measurement in liver disease patients to identify the relationship between nonspecific upper gastrointestinal symp- toms and gastric emptying function. The resu]ts are as followings; 1) Total ]iver disease patients are 28 in number, composed of acute hepatitis 3, chronic hepatitis 18, liver cirrhosis 7. 2) The GET(T1/2) of liver disease patients was delayed significantly than that of the normal volunteers. (Mean+SE;120.8+6.6 vs 89.4+5.9 mins.) 3) The GET of the symptomatic patients (N = 20 ) ivas 128.3+6.8 mins (Mean+SE), and that of the asymptomatic patients (N =8) was 101.8+13.2 mins. The symptomatic patients have delayed GET in 10 patients and asymptomatic patients have delayed GET in 3. 4) The GET of the patients who have elevated serum transaminase level higher than twice of normal is delayed significantly than that of the patients who have serum transaminase level lower than twice of normal. (Mean+SE; 143.4+2.6 vs 110.0+7.4 mins.)

저산소성 허혈성 뇌손상을 유발시킨 어린 백서에서 Myeloperoxidase 측정 검사

양혜정(Hae Joung Yang),피대훈(Dae Hun Pee),임지혜(Ji Hye Lim),최병민(Byung Min Choi),이기형(Kee Hyoung Lee),은백린(Baik-Lin Eun) 대한소아신경학회 2002 대한소아신경학회지 Vol.10 No.2

목 적 : 예전에는 뇌경색 부위에서 발견되는 백혈구를 단지 뇌손상에 뒤따르는 생리적인 반응으로만 생각하였으나 최근 10년 사이 재관류 손상에서도 백혈구에 의한 염증 작용이 중요한 역할을 한다고 알려지면서 이들의 역할에 대한 연구가 새롭게 이루어지고 있다. PML의 존재는 세포질내 과립에서 분비되는 MPO를 생화학적으로 측정함으로서 증명할 수 있는데 저자들은 미성숙 뇌에서 저산소성 허혈증에 의한 뇌손상이 발생할 때 백혈구가 침윤되는 과정을 MPO 측정 검사를 통하여 관찰하였고, P와 L-selectin 억제제인 Fucoidin을 투여한 후 MPO의 변화를 확인하였다. 방 법 : 생후 7일된 어린 흰쥐를 사용하여 우측총 경동맥을 전기 응고시켜 자르고 8% 산소에 노출시켰다. 저산소 노출 후 회복 시간에 따라 동물을 희생시키고 뇌를 추출하여 뇌조직 1 g당 10mL의 20 mM potassium Phosphate buffer(pH 7.4)를 첨가하여 50초간 분쇄하였다. 각각의 균질회된 조직 샘플들은 4℃에서 20분 동안 원심 분리하여 상층액을 제거한 후, 침전물은 처음 조직량에 따라 조직 1 g당 10 mL의 0.5% cetylditrimethylethyl ammonium bromide(wt/vol)가 첨가된 50 mM potassium phosphate buffer(pH 6.0)를 첨가하였다. Vortex를 이용하여 buffer와 침전물을 잘 섞고 60℃수조에서 120분 동안 방치하였다. 그 후 각 조직 샘플들을 4 watts에서 음파처리하고 4℃에서 15분 동안 원심 분리를 시행하여 상층액을 새로운 tube에 옮겼다. MPO 측정검사를 위한 MPO reaction buffer는 50 mM potassium phosphate buffer(pH 6.0) 100 mL에 0.53 mM odianisidine edihydrochlorde와 0.0005% HO를 섞어 만들었다. MPO reaction solution 2.9 mL에 각각의 MPO sample 0.1 mL을 첨가하여 460 nm의 파장에서 5분 동안 MPO에 다른 흡광도 차이를 관찰하였다. 결 과 : 조직내 백혈구 침윤의 지표로 측정한 MPO 활성도는 대조군에서는 미미하였으나 총 경동백을 절단한 우측 대뇌군에서는 허혈 및 저산소증 유발 후 8시간째부터 현저히 증가되기 시작하여 24시간 경과 후 발현이 가장 높았으며, Fucoidin 50 mg/kg으로 전처치한 약물 실험군에서는 MPO 활성도가 현저히 감소하였다. 결 론 : 백혈구는 미성숙 뇌의 저산소성 허혈증에 의한 뇌손상에서 중요한 매개체 역할을 하며, 백혈구의 생화학적 활성도를 나타내는 MPO 활성도는 저산소성 허혈성 뇌손상의 정도를 측정하는 지표로 이용될 수 있다고 생각된다. Purpose : Neutrophils found around an infarcted area in the brain was once considered as only the physiologic response following the brain injury, but recent studies have shown that inflammatory responses by neutrophils play an important role in the reperfusion injury. The presence of ploymorphonuclear leukocytes(PML) is proven by biochemical assay of myeloperoxidase(MPO) Secreted in the cytoplasmic granules. We observed the process of PML infiltration on hypoxic-ischemic brain injury of immature rats by the assay of MPO activity and changes of the MPO activity after the administration of fucoidin, inhibitor of P- and L-selectin. Methods : We used a well characterized model of the brains of 7 day-old-rats, which had unilateral hypoxic and ischemic injuries(HI). Those injuries were induced by unilateral carotid artery ligation followed by timed exposure to hypoxic inspiratory gas mixture(8% O). MPO activity was measured in the brain tissue homogenates of HI rats(n=18) at 0, 2, 8, 24 and 48 hrs and in rats that received fucoidin immediately before and again after hypoxia(50 mg/kg, n=6) at 8 and 24 hrs. Controls(n=2) were rats with neither hypoxia nor ischemia. The brain samples were homogenized in 20 mM potassium phosphate buffer(pH 7.4) for 50 secs. The homogenate was centrifuged at 14,000 g at 4℃ for 15 mins and the supernatant was discarded. The tissue was pulverized, weighed, and suspended in 1 mL of 50 mM potassium phosphate buffer solution(pH 6.0) contatining 0.5% cetylditrimethylammonium bromide(wt/vol). The tissue was sonicated and centrifuged at 10,000 g for 15 mins. 200 µL of the supernatant was mixed with 1 mL of 50 mM potassium phosphate buffer solution(pH 6.0) containing 10 μL of 1.325 mM o-dianisidine hydrochloride and 170 µL of 3% hydrogen peroxide(vol/vol). Changes in absorbance at 460 nm were measured for 5 mins by using microplate reader. One unit of MPO activity was defined as that degrading 1 µmol peroxide/min at 25℃, and the result was expressed as units of MPO/100 gm tissue. Results : In HI rats, MPO activity increased at 2 hrs after HI and peaked at 24 hrs in the right hemisphere. In rats with fucoidin treatment immediately before and again after hypoxia, the MPO activity significantly decreased in both hemispheres compared with HI rats(P<0.05). MPO activity in the tissue of control rats was insignificant. Conclusion : The dynamic changes of the MPO activity suggest the important role of PMN on hypoxic-ischemic brain injuries in immature rats. MPO activity could be used as an index of the severity of injuries of hypoxic-ischemic brains.

성상세포종에서 등급에 따른 p53 단백 발현의 차이

기근홍,양정원,이승학,이민오,성정희 조선대학교 2001 The Medical Journal of Chosun University Vol.26 No.1

Background and Objectives: Mutation or inactivation of the p53 is important mechanism in a wide variety of human tumors. The purpose of this study is to investigate the relationship between expression amount of p53 protein and the grade of astrocytic gliomas. Materials and Methods: This study analyzes 40 paraffin-embedded astrocytic glioma, including 10 cases of low grade, 20 cases of high grade, and 10 cases of maligant glioma (glioblastoma multiforme) were used to analyze the status of abnormal accumulation of wild type of p53 protein. The evaluation of the immunostaining result was based on the percentage of positive neoplastic cells. Results: Average positive cell rate of p53 protein were 4.2%, 35.4% and 16.2% in low grade astrocytoma, high grade astrocytoma and glioblastoma multiforme, respectively. Conclusion: p53 gene mutations were correlated with histologic grade of glial tumors. High grade and glioblastoma multiforme showed higher positive cell rate than low grade astrocytoma. These results suggest that the high positive rates of p53 protein is related to the poor prognosis.

一酸化炭素의 除毒에 關한 硏究 : 1. Carboxyhemoglobin의 解離에 미치는 酸素解離促進藥物의 影響 I. Effects of Hemoglobin-0₂Affinity-Reducing Agents on the Dissociation of Carboxyhemoglobin

李民化,李起榮 全南大醫大 1978 전남의대학술지 Vol.15 No.1

인간의 혈장아포지단백 A-I에 특이성을 지닌 단일클론항체 A-I30의 light chain의 가변부위를 coding하는 cDNA의 클로님

이상한,우기민,조만희,장예진,김창세,김정경 순천향의학연구소 1997 Journal of Soonchunhyang Medical Science Vol.3 No.2

I prepared a monoclonal antibody (mAb) A-l30 to HDL apolipoprotein A-l with the ultimate goals of expressing the valuable immunodiagnostic single-chain Fv (scFv) in Escherichia coli. The binding specificity of mAb A-l30 was determined by Western blot analysis. From the hybridoma cell line secreting mAb A-l30, poly(A)+ RNA was prepared and used as a template for cDNA synthesis and cloning. The nucleotide sequence analyses revealed that the variable regions of the heavy and light chains were members of mouse heavy chain subgroup ⅡA and κ light chain subgroup Ⅱ, respectively. Comparison of the nucleotide sequences with mouse immunoglobulin genes listed in the GenBank data base showed that the cDNAs have not been previously reported.