클렌부테롤 경피흡수제제의 개발

최한곤,권기철,정시영,이종달,용철순 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective B_(2)-adrenergic receptor stimulant, has been introduced as a polent bronchodilator for patients with bronchial asthma, asthma, chronic obstructive bronchial disease. For the development of transdennal systems containing clenbuterol, two limiting factors ? long lag time and low flux - must be overcome. In this studym we altempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of elenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Futhermore, the clenbuterol patch composed of 15% clenbuterol. 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levelsin in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.

지방산, 지방 알코올 및 프로필렌글리콜이 클렌부테롤의 경피투과에 미치는 영향

이영대,권기철,정시영,이종달,용철순 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-

Clenbuterol, a selective β_(2)-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic bronchitis and pulmonary emphysema. For the purpose of developing a transdermal preparation for clenbuterol, we attempted to select an optimal solvent system and permeation enhancer among fatty acids and fatty alcohols which are known to accelerate the penetration of various drugs in permeation experiments using hairless mouse skin and Franz diffusion cell. Apparent partition coefficient of clenbuterol was increased as pH of buffer solution was increased and solubility of clenbuterol was increased as the percent of propylene glycol(PG) in buffer solution(pH10) was increased. Permeability of clenbuterol from different buffer(pH 10)/PG solvent mixtures was decreased as the percent of PG in pH 10 buffer solution was increased and among the various enhancers studied, lauryl alcohol was found to be the most effective enhancer, increasing the permeability of clenbuterol approximately 76-fold compared with control. Lauryl alcobol(0-2%) enhanced the permeability of clenbuterol concentration-dependently. In this study, the optimal solvent system for the penetration of clenbuterol was found to be 50/50 buffer(pH 10)/PG solvent mixture containing 2% lauryl alcohol.

Early Recognition of Pediatric Strokes in the Emergency Department: Epidemiology, Clinical Presentation, and Factors Impeding Stroke Diagnosis in Children

Si Qi Tan(Si Qi Tan),Wen Qi Cher(Wen Qi Cher),Shu-Ling Chong(Shu-Ling Chong),Angelina Su Yin Ang(Angelina Su Yin Ang ),Sashikumar Ganapathy(Sashikumar Ganapathy ),Derrick Wei Shih Chan(Derrick Wei Shi 대한소아신경학회 2022 대한소아신경학회지 Vol.31 No.1

Purpose: Strokes are challenging to diagnose in pediatric emergency departments (EDs) as level of suspicion is low and atypical presentations are common. We analyzed clinical features, epidemiology and factors of delayed identification in arterial ischemic strokes (AIS) and hemorrhagic strokes (HS). Methods: Single-center retrospective cohort study of children aged between 29 days and 18 years old diagnosed with stroke between July 2016 to June 2021. Results: Among 36 children, 11 (30.5%) had AIS, 25 (69.4%) had HS. Median age for AIS was 9 years (interquartile range [IQR], 2 to 9) and HS 9 years (IQR, 1 to 11.5) (P=0.715). Focal neurological deficit was seen in 72.7% of AIS and 20% of HS (P=0.006). Only 18.2% of AIS and 52.0% of HS presented within 6 hours of symptoms. Median time from symptom onset to ED presentation was 24 hours (IQR, 12 to 28) for AIS and 7 hours (IQR, 1.8 to 48) for HS (P=0.595). Most (85.6%) arrived by own transport. Median time from presentation to neuroimaging was 7 hours (IQR, 0.9 to 7) for AIS and 4.8 (IQR, 1.3 to 16.8) hours for HS (P=0.376). Eleven patients, 9/25 (36.0%) HS and 2/11 (18.2%) AIS, did not have stroke as differential diagnosis at ED (P=0.714). Common initial diagnoses were viral illness or headaches. On univariate analysis, age <1 (odds ratio [OR], 17.5; 95% confidence interval [CI], 1.2 to 250.4; P=0.035) and absence of focal neurological deficit (OR, 13.091; 95% CI, 1.5 to 117.9; P=0.022) were significant factors for delayed identification. Conclusion: Index of suspicion for pediatric strokes among caregivers and clinicians should be increased. Public awareness campaigns are recommended.

Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer

Si-Qi Dong,Tong-Min Wang,Jiang-Bo Zhang,Yong-Qiao He,Wen-Qiong Xue,Zi-Yi Wu,Da-Wei Yang,Lian-Jing Cao,Jing-Wen Huang,Xi-Zhao Li,Pei-Fen Zhang,Xiao-Hui Zheng,Wei-Hua Jia 대한암학회 2021 Cancer Research and Treatment Vol.53 No.3

Purpose Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients.Materials and Methods Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model.Results We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression.Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

중국 학점은행제의 현황과 미래

Si Qi Yao,고형일(Hyung Yeel Koh) 전남대학교 교육문제연구소 2013 교육연구 Vol.36 No.-

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients

Si-Qi Tang,Ling-Long Tang,Yan-Ping Mao,Wen-Fei Li,Lei Chen,Yuan Zhang,Ying Guo,Qing Liu,Ying Sun,Cheng Xu,Jun Ma 대한암학회 2021 Cancer Research and Treatment Vol.53 No.2

Purpose The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. Materials and Methods Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software.Results Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031).Conclusion This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

miR-1246 inhibits NFATc1 phosphorylation and regulates Th17 cell activation in the pathogenesis of severe alopecia areata

Si-si Qi,Ying Miao,You-yu Sheng,Rui-ming Hu,Jun Zhao,Qin-ping Yang 대한피부과학회 2023 Annals of Dermatology Vol.35 No.1

Background: We found microRNA (miR)-1246 to be significantly differentially expressedbetween severe active alopecia areata (AA) patients and healthy individuals. Objective: To explore the role and mechanism of miR-1246 in severe AA. Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ Tcells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistryassays. Peripheral CD4+ T cells from the AA patients were transfectedwith lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis wereused to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclearreceptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylatedNFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA wasused to measure cytokine levels. Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantlyincreased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples. NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cellsbut not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltratinginflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA,overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1,ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in theCD4+IL-17+ cells proportion and the IL-17F level. Conclusion: miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may bebeneficial in the severe AA treatment.

Empirical seismic vulnerability probability prediction model of RC structures considering historical field observation

Si-Qi Li,Hong-Bo Liu,Ke Du,Jia-Cheng Han,Yi-Ru Li,Li-Hui Yin 국제구조공학회 2023 Structural Engineering and Mechanics, An Int'l Jou Vol.86 No.4

To deeply probe the actual earthquake level and fragility of typical reinforced concrete (RC) structures under multiple intensity grades, considering diachronic measurement building stock samples and actual observations of representative catastrophic earth shocks in China from 1990 to 2010, RC structures were divided into traditional RC structures (TRCs) and bottom reinforced concrete frame seismic wall masonry (BFM) structures, and the empirical damage characteristics and mechanisms were analysed. A great deal of statistics and induction were developed on the historical experience investigation data of 59 typical catastrophic earthquakes in 9 provinces of China. The database and fragility matrix prediction model were established with TRCs of 4,122.5284×104 m2 and 5,844 buildings and BFMs of 5,872 buildings as empirical seismic damage samples. By employing the methods of structural damage probability and statistics, nonlinear prediction of seismic vulnerability, and numerical and applied functional analysis, the comparison matrix of actual fragility probability prediction of TRC and BFM in multiple intensity regions under the latest version of China’s macrointensity standard was established. A novel nonlinear regression prediction model of seismic vulnerability was proposed, and prediction models considering the seismic damage ratio and transcendental probability parameters were constructed. The time-varying vulnerability comparative model of the sample database was developed according to the different periods of multiple earthquakes. The new calculation method of the average fragility prediction index (AFPI) matrix parameter model has been proposed to predict the seismic fragility of an areal RC structure.

Numerical Study on Performance of Prefabricated RCS Joint under Normal Temperature and Fire

Qi Si,Zhihong Pan 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.11

To study the mechanical behavior and fire resistance of the prefabricated reinforced concrete column and steel beam (RCS) joints with endplate, this paper presented a numerical investigation on the joints under normal temperature and fire. The full 3D solid finite element models were implemented in ABAQUS. The simulated results show that under normal temperature, the yield moment and initial rotation stiffness increase with the increase of the endplate thickness, the failure mode changes from deformation of the endplate to yield of the extensional part. Increasing the thickness of stiffeners and changing the form of stiffeners can effectively improve the yield moment of the joint, but the initial rotational stiffness keeps invariant basically. Under fire condition, the load ratio has a significant effect on the fire resistance of the prefabricated RCS joint; the thickness of the endplate and stiffener, the stiffener form have less influence on the fire resistance of the joint.

1930년대 상하이 영화 < 신여성 >의 패션 연구 -여성상 분석을 중심으로-

호사기 ( Si Qi Hu ),강혜승 ( Hae Seung Kang ) 커뮤니케이션디자인학회 2016 커뮤니케이션 디자인학연구 Vol.54 No.-

이 논문은 1930년대 상하이 사회와 영화 < 신여성 >의 관계를 고찰하고, 이를 통해 영화에 나타난 여성상을 세 가지로 분류하고 각각의 패션의 특성을 분석하였다. 만주사변 이후 1930년대의 상하이 영화는 국가이념을 전파하기 위한 장치로써 활용되었고, 민족주의를 앞세워 문화 탄압을 가하였다. 좌익 지식인들은 이에 대응하여 시대와 사회를 비판하는 좌익영화의 제작을 통해 저항하였다. 국민당과 좌익 지식인으로 대별되는 정치 이념에 따라 각기 다른 여성상이 추구되었다. 영화 < 신여성 >에서 여성상은 등장인물의 사상, 직업, 생활환경, 성격에 따라 모순적 여성상, 진보적 여성상, 향락적 여성상으로 분류되었고, 패션 표현을 통해 차별화되었다. 패션 분석을 통해 상하이를 둘러싼국민당 정부의 문화 통제와 좌익 영화인들 사이의 긴장 관계가 여성의 패션으로 응집되어 표출된 것을 밝혔다. 이 시기 사회문화적 흐름과 여성 패션에 대한 탐구는 현재 중국이 지닌 과제인 주체적 문화의식 형성에 시사점을 제공한다고 사료된다. This paper looks into the society of 1930s Shanghai and the film < Modern Women >, and divided the women that were depicted in the film into 3 images and the features of their fashion. After the Manchurian Incident, Shanghai films were used as a political tool for the dissemination of nationalistic beliefs, and were also used to further suppress culture using nationalism. The intellectual left fought against this by producing films representing their beliefs that criticized the government. Two different images of women were represented by the National Party and the intellectual left. In the film < Modern Women >, women were divided by their political beliefs, profession and personality into contradictory feminists, progressives and hedonists, and further made the point by using fashion as visual representation. Through this analysis, I will present the culture and suppression of the National party concerning Shanghai, and the ensuing political friction that was caused between them and the intellectual left. I think that the analysis of the socio-political discourse during this time period and women’s fashion had implications in the formation of independent culture of China.