• Title/Summary/Keyword: drug design

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Understanding the RNA-Specificity of HCV RdRp: Implications for Anti-HCV Drug Discovery

  • Kim, Jin-young;Chong, You-hoon
    • Bulletin of the Korean Chemical Society
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    • v.27 no.1
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    • pp.59-64
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    • 2006
  • Unlike other viral polymerases, HCV RNA-dependent RNA polymerase (RdRp) has not been successfully inhibited by nucleoside analogues presumably due to its strong substrate specificity for RNA. Thus, in order to understand the RNA-specificity of HCV RdRp, the structural characteristics of the active site was investigated. The hereto unknown 2-OH binding pocket at the active site of RdRp provides invaluable implication for the development of novel anti-HCV nucleoside analogues.

Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from Legionella pneumophila (strain Paris): An In Silico Approach

  • Hasan, Md. Anayet;Mazumder, Md. Habibul Hasan;Khan, Md. Arif;Hossain, Mohammad Uzzal;Chowdhury, A.S.M. Homaun Kabir
    • Genomics & Informatics
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    • v.12 no.4
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    • pp.268-275
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    • 2014
  • The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.

Comparison of the Factors Associated with the Habitual Drug Use among Adolescents from Multicultural and Non-multicultural Families in South Korea: Analysis of Data from the 14~15th (2018~2019) Korea Youth Risk Behavior Wed-based Survey (다문화 청소년과 비다문화 청소년의 습관적 약물 경험 관련 요인 비교: 제14~15차(2018~2019년) 청소년건강행태온라인조사를 이용하여)

  • Sung, Sumi;Park, Seul Ki;Min, Yul Ha
    • Journal of the Korean Society of School Health
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    • v.34 no.1
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    • pp.1-12
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    • 2021
  • Purpose: Growing evidence indicates that adolescents from multicultural families are more vulnerable to drug use than those from non-multicultural families. This study aimed to compare the factors associated with the habitual drug use among adolescents from multicultural and non-multicultural families. Methods: A descriptive cross-sectional design was employed. Data were obtained from the 14~15th (2018~2019) Korea Youth Risk Behavior Web-based Survey. Overall, 91,443 multicultural (n=1,725) and non-multicultural adolescents (n=89,718) were included. Data were analyzed using descriptive statistics, univariate analysis, and logistic regression analysis. Results: The multicultural adolescents engaged in more habitual drug use than did non-multicultural adolescents. In both groups, those who currently drank, experienced violent victimization, had sexual experiences, and did not live with their family were at greater risk of engaging in habitual drug use. The odds ratios of these factors were higher in multicultural adolescents than in non-multicultural adolescents. In non-multicultural adolescents, those who were boys, had experienced depression and suicidal ideation, perceived their body image as normal, overweight, or obese, and had poor subjective health status were at greater risk of engaging in habitual drug use. Conclusion: These results highlight the need to develop customized strategies for adolescents from both multicultural and non-multicultural families to reduce and prevent their habitual drug use.

Rapid Detection for Salmonella spp. by Ultrafast Real-time PCR Assay (Ultrafast Real-time PCR법을 이용한 살모넬라의 신속 검출)

  • Kim, Seok Hwan;Lee, Yu-Si;Joo, In-Sun;Kwak, Hyo Sun;Chung, Gyung Tae;Kim, Soon Han
    • Journal of Food Hygiene and Safety
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    • v.33 no.1
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    • pp.50-57
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    • 2018
  • Salmonella continue to be a major cause of food poisoning worldwide. The rapid detection method of food-borne Salmonella is an important food safety tool. A real-time polymerase chain reaction (PCR) has been used as a rapid method for the detection of pathogens. It has been recently reported that NBS LabChip real-time PCR is a novel, ultrafast, and chip-type-convenient real-time PCR system. We developed the assay method based on NBS LabChip real-time PCR for the rapid detection of Salmonella, which its reaction time was within 20 minutes. Two target genes (invA and stn) were selected to design target specific primers and probes. The new method was validated by checking specificity and sensitivity (limit of detection). This study included forty-two target and twenty-one non-target strains to assess the specificity. This assay was able to identify the 42 Salmonella strains correctly. The limit of detection (LOD) was $10^1copies/{\mu}L$ in Salmonella genomes DNA, while LOD incubated for 4 hr in the inoculated sausage sample ranged from $10^1CFU/g$ to $10^2CFU/g$ as an inoculated cell count. The assay developed in this study could be applied for the investigation of food poisoning pathogens.

Swelling and Drug Release Characteristics of PVP Hydrogel Polymerized by $\gamma$-Irradiation Method (김마선 조사법으로 합성한 PVP하이드로겔의 팽윤과 약물방출특성)

  • 심창구;오정숙;신병철
    • YAKHAK HOEJI
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    • v.37 no.5
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    • pp.511-519
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    • 1993
  • The short and variabke transit of drug throught GI tracj and the inter-and intra-subject variations of the transit restrict the sustained drug absorption after oral adminstration. These restrictions may be solved by retaining the dosage forms in the stomach. Then the dosage form will act as a platform which releases the drug slowly and makes the GI absorption occur for a long time. In this study, as the platforms, PVP hydrogels were synthesized by chemical and y-irradiation method in the cylindrical test tube. The chemical method means the synthesis of the hydrogel by heating the mixed solution of N-vinyl-2-pyrrolidone [monomer], acrylated albumin [crosslinking agent], 2, 2'-agobis(2-methylpropionitrile) [initiator] and proxyphylline [drug] at $65^{\circ}C$ for 5 hr. The $\gamma$-irradiation method means the synthesis of the hydrogel by irradiation with $^{60}$ Co $\gamma$-ray of the mixed solution of the monomer, acrylated albumin, and flurbiprofen [drug] at room temperature with total 0.2 Mrad for 3 hr. Our intention is to design the hydrogel tablet (diameter : 1.20 cm, thickness : 0.60 cm) which swells in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the period of drug release. After releasing drug, the hydrogel should be degraded by the enzymeatic digestion in the stomach, or by hydrolysis and eventually solubilized. Thus, in votro tests were performed to examine the factors that affect swelling and drug release from the PVP hydrogels. Experimental results show that the hydrogels swell to a size larger than the diameter of the pylorus(l.3$\pm$0.7 cm) and the hydrogel prepared by the chemical method is digested by pepsin. But the hydrogel prepared by the $\gamma$-irradiation method was not digested by the pepsin and just collapsed with time. Thus, the swelling of the hydrogel synthesized by $\gamma$-irradiation was independent albumin acrylation time and pepsin concentration. But drug content and radiation dose affected the swelling and drug release kinetics of the hydrogel. Drug release from the hydrigels was prolonged up to about 24 hr. Therefore, it was concluded that by adjusting these factors, the albumin-crosslinked PVP hydrogel synthesized by $\gamma$-irradiation method is expected to be retained in the stomach for up to 60hr and be a potential platform of drugs for long-term GI absorption.

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A Goneral Procedure for Testing Equivalence

  • Sung Nae Kyung
    • Communications for Statistical Applications and Methods
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    • v.5 no.2
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    • pp.491-501
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    • 1998
  • Motivated by bioequivalence studies which involve comparisons of pharmaceutically equivalent dosage forms, we propose a more general decision rule for showing equivalence simultaneously between multiple means and a control mean. Namely, this testing procedure is concerned with the situation in that one must make decisions as to the bioequivalence of an original drug product and several generic formulations of that drug. This general test is developed by considering a spherical confidence region, which is a direct extension of the usual t-based confidence interval rule formally approved by the U.S. Food and Drug Administration. We characterize the test by the probability of rejection curves and assess its performance via Monte-Carlo simulation. Since the manufacturer's main concern is the proper choice of sample sizes, we provide optimal sample sizes from the Monte-Carlo simulation results. We also consider an application of the generalized equivalence test to a repeated measures design.

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Modeling for Multilayered Polymer Matrix Drug Delivery Device (다층구조로 된 고분자 제형의 약물 방출에 대한 모델링)

  • Byun, Young-Rho;Jeong, Seo-Young;Kim, Young-Ha
    • Journal of Pharmaceutical Investigation
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    • v.19 no.2
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    • pp.87-92
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    • 1989
  • The multilayered monolithic type transdermal delivery device has been designed and analyzed by a numerical analysis. The device consists of three layered polymer matrices which posess the different diffusion parameters, respectively. The purpose of this study was to design an ideal transdermal drug delivery device which is capable of initial burst and zero order release later on. Numerical modelings were simulated for a dispersed and a dissolved multilayered monolithic system. The results showed that the dispersed multilayered monolithic system could meet the requirements for an ideal transdermal delivery device.

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Comparison of the Solution Structure of Vancomycin with Its X-ray Crystallographic Structure

  • Lee, Chul-Hoon;Kyung, Han-Soo;Lim, Yoong-Ho
    • Journal of Microbiology and Biotechnology
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    • v.10 no.5
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    • pp.733-736
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    • 2000
  • Since pathogens resistant against vancomycin occur rapidly, the development of a new drug is needed. To make a new drug based on a rational drug design, the structural study of vancomycin is necessary. Accordingly, this study reports on a comparison of the solution structure of vancomycin determined by NMR spectroscopy, which was performed in the present work, with the X-ray crystallographic structure previously deposited in the Protein Data Bank (PDB).

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A Study on Effects of EGCG and Design Parameter for Drug-Eluting Biodegradable Polymer Stents (약물-용출 생분해성 고분자 스텐트를 위한 EGCG와 디자인 파라미터의 영향에 대한 연구)

  • Jung, T.G.;Lee, J.H.;Lee, J.J.;Hyon, S.H.;Han, D.W.
    • Journal of Biomedical Engineering Research
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    • v.34 no.3
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    • pp.111-116
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    • 2013
  • Finite element analysis(FEA) has been extensively applied in the analyses of biomechanical properties of stents. Geometrically, a closed-cell stent is an assembly of a number of repeated unit cells and exhibits periodicity in both longitudinal and circumferential directions. This study concentrates on various parameters of the FEA models for the analysis of drug-eluting biodegradable polymeric stents for application to the treatment of coronary artery disease. In order to determine the mechanical characteristics of biodegradable polymeric stents, FEA was used to model two different types of stents: tubular stents(TS) and helicoidal stents(HS). For this modeling, epigallocatechin-3-O-gallate (EGCG)-eluting poly[(L-lactide-co-${\varepsilon}$-caprolactone), PLCL] (E-PLCL) was chosen as drug-eluting stent materials. E-PLCL was prepared by blending PLCL with 5% EGCG as previously described. In addition, the effects of EGCG blending on the mechanical properties of PLCL were investigated for both types of stent models. EGCG did not affect tensile strength at break, but significantly increased elastic modulus of PLCL. It is suggested that FEA is a cost-effective method to improve the design of drug-eluting biodegradable polymeric stents.

Pilot Study of a Brief WeChat Intervention in China to Increase Students' Willingness to Assist a Flushing Student to Reduce Alcohol Use

  • Zhang, Fan;Yuen, Lok-Wa;Ding, Lanyan;Newman, Ian M.;Shell, Duane F.
    • Journal of Preventive Medicine and Public Health
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    • v.51 no.6
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    • pp.320-325
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    • 2018
  • Objectives: This pilot study tested the effectiveness of a brief alcohol-related intervention delivered by the social media app WeChat to teach about ethanol-induced facial flushing and increase the willingness of students who see another student flushing to suggest that he or she should reduce or stop drinking. In the context of Chinese drinking culture, it is sometimes socially difficult to refuse a drink, even when experiencing physical discomfort, such as flushing. Methods: Classrooms of students in a medical university in China were randomly assigned to the intervention or control group. Students in the intervention group were invited to view 3 alcohol education lessons on WeChat during a 2-week period. A pretest and posttest before and after the 2-week period assessed changes in students' willingness to intervene if they saw someone flush while drinking. Data were collected about students' alcohol use and their ratings of the lessons. Results: Mixed-design analysis of variance yielded a significant time-by-treatment interaction effect on the variable of willingness to suggest that a flushing person stop or slow down their drinking, and the change was significant between the intervention and control groups. One-way analysis of covariance yielded a significant treatment effect at the posttest, after controlling for the pretest score. Students rated the lessons above the midpoint of the scale for being informative, interesting, and useful. Conclusions: The pilot study showed that a brief alcohol-related intervention delivered by WeChat could produce a measurable positive change in the willingness of university students to suggest that a student who flushes should stop drinking. This pilot study also suggested improvements for future lessons and evaluation design.