• Title/Summary/Keyword: Drug screen

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A Validation Study for the Practical Use of Screening Scale for Potential Drug-use Adolescents(SPDA) (청소년 약물사용 잠재군 선별척도(SPDA) 활용을 위한 타당화 연구)

  • Lee, Ki-Young;Kim, Young-Mi;Im, Hyuk;Park, Mi-Jin;Park, Sun-Hee
    • Korean Journal of Social Welfare
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    • v.57 no.3
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    • pp.305-335
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    • 2005
  • This paper is a result from validation study for SPDA(A Screening Scale For Potential Drug-use Adolescents) created in 2003 and newly developed during 2004. SPDA aims to screen adolescents in their early stage of drug-use and to help practitioners make a preventive approach for the adolescents. 4307 junior and senior high school students were selected as primary research subjects by stratified and quota sampling methods. 305 adolescents on probation were also selected as a comparison group and asked to answer the same questionnaire. Reliability for SPDA recorded 0.914, which proved to be better than previous year's (0.898). Exploratory and confirmatory factor analyses to test construct validity proved that SPDA could be divided into 7 factors and that each factor structure of SPDA could be a proper measurement model with high level of fitness and factor loadings. Discriminant analysis to test predictive validity confirmed that SPDA could classify the adolescents excellently by the frequency of drug-use, with hit ratio of 86.6 percent(78.8% and 87.4% for junior and senior high school students respectively). For concurrent validity test, Hare Home Self-Esteem Scale, Hare School Self-Esteem, Zuckerman-Kuhlman Sensation-seeking Scale were employed to find correlation with SPDA and all the three scales had significant Pearson correlation coefficients with SPDA. Known-groups validity test indicated that SPDA had an adequate power to classify out adolescents on probation from those in schooling, with a hit ratio of 71.8 percent. Cut-off point to detect adolescents with high risk of substance use was 77, which indicated approximately T score, 55 (0.5 SD), satisfying sensitivity, specificity, and efficiency criteria.

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Mad1p, a Component of the Spindle Assembly Checkpoint in Fission Yeast, Suppresses a Novel Septation-defective Mutant, sun1, in a Cell Division Cycle

  • Kim In G.;Rhee Dong K.;Jeong Jae W.;Kim Seong C.;Won Mi S.;Song Ki W.;Kim Hyong B.
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2002.10a
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    • pp.162-172
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    • 2002
  • Schizosaccharomyces pombe is suited for the study of cytokinesis as it divides by forming a septum in the middle of the cell at the end of mitosis. To enhance our understanding of the cytokinesis, we have carried out a genetic screen for temperature-sensitive S. pombe mutants that show defects in septum formation and cell division. Here we present the isolation and characterization of a new temperature-sensitive mutant, sun1(septum uncontrolled), which undergoes uncontrolled septation during cell division cycle at restrictive temperature $(37^{\circ}C)$. In sun1 mutant, actin ring and septum are positioned at random locations and angles, and nuclear division cycle continues. These observations suggest that the sun] gene product is required for the proper placement of the actin ring as well as precise septation. The sun] mutant is monogenic recessive mutation unlinked to previously known various cdc genes of S. pombe. In a screen for $sunl^+$ gene to complement the sun] mutant, we have cloned a gene, $susl^+$(suppressor of sun1 mutant), that encodes a protein of 689 amino acids. The predicted amino acid sequence of $susl^+$ gene is similar to the human hMadlp and Saccharomyces cerevisiae Mad1p, a component of the spindle checkpoint in eukaryotic cells. The null mutant of $susl^+$ gene grows normally at various temperatures and has the increased sensitivity to anti-microtubule drug, while $susl^+$ mutant shows no sensitivity to microtubule destabilizing drugs. The putative S. pombe Sus1p directly interacts with S. pombe Mad2p in yeast two-hybrid assays. These data suggest that the newly isolated susr gene encodes S. pombe Mad1p and suppresses sun] mutant defective in controlled septation in a cell division cycle.

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Screening of Potential Anticancer Compounds from Marketed Drugs: Aripiprazole, Haloperidol, Miconazole, and Terfenadine Inhibit Cytochrome P450 2J2 (시판 약물의 시토크롬 2J2 약물대사효소 저해능 탐색)

  • Liu, Kwang-Hyeon
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1558-1564
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    • 2011
  • Cytochrome P450 2J2 (CYP2J2) plays important roles in the metabolism of endogenous metabolites such as arachidonic acid as well as therapeutic drugs. CYP2J2 is overexpressed in human cancer tissues and cancer cell lines, as well as in epoxyeicosatrienoic acids (EETs) and CYP2J2-mediated metabolites, and prevent apoptosis of cancer cells. This study aimed to screen marketed drugs for inhibitory potential on CYP2J2 isoforms using human liver microsomes. The initial screen isolated 4 compounds, from 120 marketed drugs, that inhibited the CYP2J2-mediated astemizole O-demethylation more than 50% in the following the order: haloperidol (75%) > terfenadine (56%) > aripiprazole (55%) > miconazole (52%). Miconazole strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=11.2 ${\mu}M$) and terfenadine hydroxylation ($IC_{50}$=2.2 ${\mu}M$), and terfenadine also inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=13.6 ${\mu}M$) in a dose dependent manner. The present data suggest that these drugs are potential candidates for further evaluation for their anti-cancer activities.

A Screening Method for Src Homology 3 Domain Binding Blockers Based on Ras Signaling Pathway

  • Ko, Woo-Suk;Yoon, Sun-Young;Kim, Jae-Won;Lee, Choong-Eun;Han, Mi-Young
    • BMB Reports
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    • v.30 no.5
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    • pp.303-307
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    • 1997
  • Grb2, which is composed of a Src homology 2 (SH2) domain and two Src homology 3 (SH3) domains, is known to serve as an adaptor protein in signaling for Ras activation. Thus, a blocker of the Grb2 interactions with other proteins can be a potential candidate for an anticancer drug. In this study, we have developed a high throughput screening method for SH3 domain binding ligands and blockers. Firstly, we made and purified the glutathione S-transferase (GST)-fusion proteins with the Grb2 SH2 and SH3 domains, and the entire Grb2. This method measures the binding of a biotin-labeled oligopeptide, derived from a Grb2/SH3 binding motif in the hSos, to the GST-fusion proteins, which are precoated as glutathione S-transferase fusion protein on a solid phase. When $1\;{\mu}g$ of each fusion protein was used to coat the wells, both N- and C- terminal SH3 the domains as well as the whole of Grb2 were able to interact with the biotin-conjugated ligand peptide, while the SH2 domain and GST alone showed no binding affinity. Although N- and C- terminal SH3 domains showed an increase of binding to the ligand peptide in proportion to the amount of peptide, the GST fusion protein with Grb2 demonstrated much higher binding affinity. GST-Grb2 coating on the solid phase showed a saturation curve; 66 and 84% of the maximal binding was observed at 100 and 300 ng/$100\;{\mu}l$, respectively. This binding assay system was peptide sequence-specific, showing a dose-dependent inhibition with the unlabeled peptide of SH3 binding motif. Several other peptides, such as SH2 domain binding motifs and PTB domain binding motif, were ineffective to inhibit the binding to the biotin-conjugated ligand peptide. These results suggest that our method may be useful to screen for new anticancer drug candidates which can block the signaling pathways mediated by SH3 domain binding.

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Establishment of High Throughput Screening System Using Human Umbilical Cord-derived Mesenchymal Stem Cells

  • Park, Eu-Gene;Cho, Tae-Jun;Oh, Keun-Hee;Kwon, Soon-Keun;Lee, Dong-Sup;Park, Seung-Bum;Cho, Jae-Jin
    • International Journal of Oral Biology
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    • v.37 no.2
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    • pp.43-50
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    • 2012
  • The use of high throughput screening (HTS) in drug development is principally for the selection new drug candidates or screening of chemical toxicants. This system minimizes the experimental environment and allows for the screening of candidates at the same time. Umbilical cord-derived stem cells have some of the characteristics of fetal stem cell and have several advantages such as the ease with which they can be obtained and lack of ethical issues. To establish a HTS system, optimized conditions that mimic typical cell culture conditions in a minimal space such as 96 well plates are needed for stem cell growth. We have thus established a novel HTS system using human umbilical cord derived-mesenchymal stem cells (hUC-MSCs). To determine the optimal cell number, hUC-MSCs were serially diluted and seeded at 750, 500, 200 and 100 cells per well on 96 well plates. The maintenance efficiencies of these dilutions were compared for 3, 7, 9, and 14 days. The fetal bovine serum (FBS) concentration (20, 10, 5 and 1%) and the cell numbers (750, 500 and 200 cells/well) were compared for 3, 5 and 7 days. In addition, we evaluated the optimal conditions for cell cycle block. These four independent optimization experiments were conducted using an MTT assay. In the results, the optimal conditions for a HTS system using hUC-MSCs were determined to be 300 cell/well cultured for 8 days with 1 or 5% FBS. In addition, we demonstrated that the optimal conditions for a cell cycle block in this culture system are 48 hours in the absence of FBS. In addition, we selected four types of novel small molecule candidates using our HTS system which demonstrates the feasibility if using hUC-MSCs for this type of screen. Moreover, the four candidate compounds can be tested for stem cell research application.

Development of a Smartphone Application for Clinical Decision Making of Medication Administration (투약적용의 임상적 의사결정을 위한 스마트폰 어플리케이션의 개발)

  • Kim, Myoung-Soo;Park, Jung-Ha;Kim, Sungmin
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.15 no.3
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    • pp.1650-1662
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    • 2014
  • This study aimed to develop smartphone application contents for the medication reconciliation of high-alert medications and to evaluate the satisfaction for this application. The xcode 4.5 and ios 6.1 SDK(software development kit) were used for constructing screen of the system. After implementation during 4 weeks, thirty five ICU(Intensive Care Unit) nurses were asked function related, contents related, and usage related satisfaction using 12 items. And differences of satisfaction according to the number of daily use and the frequency of use were evaluated. Data were analyzed using descriptive analysis, ANOVA with the SPSS 18.0. We developed the formula for drug dosage calculation, the alarming procedure, and the information of the high alert medication. In the satisfaction items, the mean score of 'This application is helpful to perform drug dosage calculation' was 3.14. However, 'I satisfy this application' was relatively low as 2.94. There were no differences in satisfaction according to the daily use and frequency of use. Based on the results of this study, more advanced smartphone application for medication reconciliation of high-alert medications will provide an important platform for patient safety.

Lack of Mutation in p53 and H-ras Genes in Phenytoin Induced Gingival Overgrowth Suggests its Non Cancerous Nature

  • Jayaraman, Bhaskar;Valiathan, Gopalakrishnan Mohan;Jayakumar, Keerthivasan;Palaniyandi, Arunmozhi;Thenumgal, Siji Jacob;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5535-5538
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    • 2012
  • Background: There have been case reports of oral squamous cell carcinoma arising from gingival overgrowth induced by phenytoin - an antiepileptic drug. However, a detailed analysis for the presence of mutations in p53 and ras genes, which are the two most frequently mutated genes in cancers, in phenytoin induced gingival overgrowth tissues has hitherto not been performed. Methods: Cellular DNA isolated from twenty gingival overgrowth tissues collected from patients undergoing phenytoin therapy were amplified using primers for p53 (exons 5-8) and H-ras (exons 1-2) genes. The PCR amplicons were then gel purified and subjected to direct sequencing analysis to screen for mutations. Results: Direct sequencing of twenty samples of phenytoin induced gingival growth did not identify mutations in any of the exons of p53 and H-ras genes that were analyzed. Conclusion: Our result indicates that mutational alteration of p53 and H-ras genes is infrequent in phenytoin induced gingival growth, which thus suggests a non malignant nature of this pathology. The findings in the present study are clinically significant as a large number of epileptic patients are treated with phenytoin.

Screening on Radical Scavenging Activity of Marine Microalgae (해양미세조류의 라디칼소거활성 검색)

  • Choi, Jin-Seok;Lee, Won-Kap;Kim, Dong-Soo;Choi, Hong-Dae;Choi, Jae-Sue;Jung, Jee H.;Im, Kwang-Sik;Choi, Won-Chul;Son, Byeng-Wha
    • Korean Journal of Pharmacognosy
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    • v.31 no.2
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    • pp.252-255
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    • 2000
  • In order to screen new radical scavenging principle which is expected to be antiaging drug lead, we have investigated 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of the marine microalgae, greenalgae(10 speices), diatom (10 speices) and blue-green algae (10 speices). The significant activities$(IC_{50}:\;<100\;{mu}g/ml)$ were observed in 4 species of green algae (MA002, 006, 009, 010), 1 species of diatom (MA015) and 5 species of blue-green algae (MA017, 018, 019, 024, 025). Within the scope of family tested, MA009 $(IC_{50}:\;=78\;{mu}g/ml)$, MA015 $(IC_{50}:\;=38\;{mu}g/ml)$ and MA019 $(IC_{50}:\;=41\;{mu}g/ml)$ displayed the most significant activity. Among the marine microalgae tested at family level, cyanophycean blue-green algae was shown to be the most active family on screening of new bioactive compounds.

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Pharmacopuncture for Stroke: An Overview of Meta-Analyses (뇌졸중의 약침 치료에 대한 메타분석의 통합적 고찰)

  • Kim, Mikyung;Han, Chang-ho
    • The Journal of Internal Korean Medicine
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    • v.40 no.6
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    • pp.1081-1100
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    • 2019
  • Objectives: This study is an overview of the meta-analysis and systematic review of randomized controlled trials investigating the clinical effectiveness and safety of pharmacopuncture for patients with stroke. Methods: Core electronic databases were searched from their inception to 21 May 2019. A measurement tool to assess systematic reviews (AMSTAR 2) was applied to screen high-quality studies. The results of these studies were summarized, and additional meta-analysis was conducted. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence. Results: Sixteen studies met eligibility criteria. Four were excluded owing to insufficiency of AMSTAR 2 or low data reliability. The finally selected 12 studies were about pharmacopuncture using either a single herb extract, such as Dengzhan xixin, Sanch, Ginkgo biloba, or Acanthopanax, or a mixture of herbs, such as Compound danshen, Shenxiong, Xingnaojing, or Mailuoning. Most of the patients were from China, with acute ischemic stroke. All the studies using a pharmacopuncture versus a non-pharmacopuncture design reported the significant superiority of pharmacopuncture on every outcome measure. On the other hand, in a few studies, pharmacopuncture was inferior to active control in improving neurological deficit. Few studies reported adverse events. Conclusions: It is difficult to apply the results of this study directly to Korea, because the level of evidence is generally low and the clinical settings and social acceptance of pharmacopuncture therapy differ in Korea and China. Further studies are warranted to confirm the domestic applicability of evidence generated in China and to create evidence that supports the domestic situation.

Preliminary Evaluation of the in vitro Efficacy of 1, 2-di (Quinazolin-4-yl) Diselane against SiHa Cervical Cancer Cells

  • Huang, Yin-Jiu;Zhang, Yu-Yuan;Liu, Gang;Tang, Jie;Hu, Jian-Guo;Feng, Zhen-Zhong;Liu, Fang;Wang, Qi-Yi;Li, Dan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6301-6306
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    • 2014
  • Cervical cancer is one the most common malignancies among females. In recent years, its incidence rate has shown a rising trend in some countries so that development of anticancer drugs for cervical cancer is an urgent priority. In our recent anticancer drug discovery screen, 1, 2-di (quinazolin-4-yl)diselane (LG003) was found to possess wide spectrum anticancer efficacy. In the present work, the in vitro anticancer activity of LG003 was evaluated in the SiHa cervical cancer cell line. Compared with commercial anticancer drugs 10-hydroxycamptothecin, epirubicin hydrochloride, taxol and oxaliplatin, LG003 showed better anticancer activity. Furthermore, inhibition effects were time- and dose-dependent. Morphological observation exhibited LG003 treatment results in apoptosis like shrinking and blebbing, and cell membrane damage. Lactate dehydrogenase release assay revealed that LG003 exerts such effects in SiHa cells through a physiology pathway rather than cytotoxicity, which suggests that title compound LG003 can be a potential candidate agent for cervical cancer.