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          • SCIESCOPUSKCI등재

            Korean Pharmacogenomic Database: Pharmacogenomic Haplotype Analysis of the Korean Population and Ethnic Comparisons

            Kang,,Tae-Sun,Woo,,Sun-Wook,Park,,Hyun-Joo,Roh,,Jae-Sook The Korean Society of Applied Pharmacology 2008 Biomolecules & Therapeutics(구 응용약물학회지) Vol.16 No.2

            The major aim of the Korean Pharmacogenomic Database (KPD) is to offer to users a "bridging" function, making the search for useful information easier. This database has also been established to collect unique Korean genotype data from other databases and to directly link these data to other major databases that offer more informative data. In this way, searches for information about new drug developments and easier and faster evaluation of the more complex and larger databases are possible. The KPD is located at the National Institute of Toxicological Research homepage (http://www.nitr.go.kr/nitr/contents/m134700/view.do), and offers Korean single-nucleotide polymorphism (SNP) information for 154 genes and haplotype information. It also compares the Korean SNP and haplotype frequencies with those of the other ethnic groups registered in the International HapMap. Through the Pharmacogenomic Information and Education facility, we also provide evaluators and the public with information about the concept of pharmacogenomic information, research trends, and the drug regulations of other countries. Because the drug responses of Koreans are not necessarily the same as those of Chinese or Japanese people, it is expected that the systematic operation of the KPD will allow the definition of racial differences and various genomic biomarkers (haplotypes or SNPs) for use in bridging studies and in the approval of new drugs.

          • SCIESCOPUSKCI등재

            Comparative Drug Evaluation of Atorvastatin versus Rosuvastatin in Pharmacotherapy of Korean Patients with Dyslipidemia

            Park,,Seon-Young,Lee,,Myung-Koo,Lim,,Sung-Cil The Korean Society of Applied Pharmacology 2008 Biomolecules & Therapeutics(구 응용약물학회지) Vol.16 No.1

            Dyslipidemia is the multiple lipid metabolic disorders which is one of the high risk factors for the atherosclerotic diseases. It increases the morbidity and mortality and therefore, must be treated with antilipidemic agents. HMG-Co A reductase inhibitors (statins), one of many antidyslipidemic agents, have shown to be significant improvement from the various cholesterol levels. Especially, data from many comparative trials suggest that rosuvastatin is more effective than atorvastatin among many other statins. The aims of this study were to evaluate the efficacy and safety between rosuvastatin and atorvastatin in the treatment of Korean patients with dyslipidemia. Currently the Korean Society of Lipidology and Atherosclerosis based on the Korean health screening data suggests that Korean patients with dyslipidemia should be treated by the target cholesterol levels according to the Adult Treatment Panel III guidelines of the US National Cholesterol Education Program (NCEP-ATP III). We reviewed retrospectively all medical histories of the total 392 dyslipidemic patients with atorvastatin or rosuvastatin from June 1st, 2004 to August 31st, 2006 in Chungbuk National University Medical Center. Patients were classified as total 4 groups by the NCEP-ATP III Guidelines. The numbers of enrolled patients were each 5 mg atorvastatin (n=34), 10 mg atorvastatin (n=148), 5 mg rosuvastatin (n=94) and 10 mg rosuvastatin (n=82). In comparison between groups, rosuvastatin groups in the lowering LDL-C had better efficacies, and the results were each 22% (5 mg atorvastatin), 33.3% (10 mg atorvastatin), 35% (5 mg rosuvastatin) and 41.3% (10 mg rosuvastatin) with the dose relationship (P=0.000). Rosuvastatin groups also have shown to be more significantly reducing Total Cholesterol levels compared to atorvastatin groups with the no dose relationship (P=0.000). In the lowering of non-HDL cholesteroles, rosuvastatin groups showed significantly better efficacies than atorvastatin with the dose-relationship (P=0.000). Each medication groups did not demonstrate the differences in the changing of HDL cholesterol and triglyceride levels (P=0.096, 0.309, respectively). In conclusion, rosuvastatin was better efficacious than atrovastatin in reducing LDL-C Total Chol, and Tg. Therefore, rosuvastatin is a good antilipidemic agents for Korean patients with dyslipidemia and it can use to minimize the morbidity and mortality related to the cardiovascular diseases in Korean.

          • SCIESCOPUSKCI등재

            Korean Red Ginseng Tonic Extends Lifespan in D. melanogaster

            Kim,,Man,Su The Korean Society of Applied Pharmacology 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.3

            Aging is the single most important risk factor that increases susceptibility to many forms of diseases. As such, much effort has been put forward to elucidate the mechanisms behind the processes of aging and to discover novel compounds that retain anti-aging activities. Korean red ginseng has been used for a variety of medical purposes in eastern countries for several thousands of years. It has been shown that Korean red ginseng affects a number of biological activities including, but not limited to, anti-inflammatory, anti-oxidative and anti-diabetic pathways. However, few studies have been performed to evaluate its anti-aging effects with an in vivo system. Here Drosophila melanogaster as an in vivo model organism demonstrates that Korean red ginseng tonic extends lifespan, increases resistance to starvation stress and prevents weight gain. This data suggest that Korean red ginseng may regulate organisms' metabolism in favor of extending lifespan.

          • SCIESCOPUSKCI등재

            Extracellular Signal-Regulated Kinase Is a Major Enzyme in Korean Mistletoe Lectin-Mediated Regulation of Macrophage Functions

            Byeon,,Se-Eun,Lee,,Jae-Hwi,Yu,,Tao,Kwon,,Moo-Sik,Hong,,Sung-Youl,Cho,,Jae-Youl The Korean Society of Applied Pharmacology 2009 Biomolecules & Therapeutics(구 응용약물학회지) Vol.17 No.3

            Korean mistletoe lectin (KML) is the major component found in Viscum album var. (coloratum), displaying anti-cancer and immunostimulating activities. Even though it has been shown to boost host immune defense mechanisms, the regulatory roles of KML on the functional activation of macrophages have not been fully elucidated. In this study, regulatory mechanism of KML on macrophage-mediated immune responses was examined in terms of KML-mediated signaling event. KML clearly induced mRNA expression of tumor necrosis factor (TNF)-$\alpha$, the generation of reactive oxygen species (ROS) and phagocytic uptake in RAW264.7 cells. All of these events were strongly suppressed by U0126, whereas TNF-$\alpha$ mRNA was not diminished by SB203580 and SP600125, indicating ERK as a central enzyme managing KML-induced up-regulation of macrophage functions. Indeed, KML strongly induced the phosphorylation of ERK in a time-dependent manner without altering its total level. Therefore, these data suggest that ERK may be a major signaling enzyme with regulatory property toward various KML-mediated macrophage responses.

          • SCIESCOPUSKCI등재

            Effect of Korean Mistletoe Lectin on Gene Expression Profile in Human T Lymphocytes: A Microarray Study

            Lyu,,Su-Yun,Park,,Won-Bong The Korean Society of Applied Pharmacology 2010 Biomolecules & Therapeutics(구 응용약물학회지) Vol.18 No.4

            Korean mistletoe has a variety of biological effects, such as immunoadjuvant activities. This study investigates the effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) on human T lymphocytes to determine whether VCA acts as an immunomodulator. Purified human T-lymphocytes were cultured with VCA and RNA from each point was analyzed using Affymetrix human genome chips containing 22,500 probe sets which represents more than 18,000 transcripts derived from 14,500 human genes. As a result, there was a striking upregulation of genes coding for chemokines. Seventeen genes out of 50 coding for proteins with chemokine activity were upregulated including CXCL9 and IL-8 which are related to the treatment of cancer. In addition, 28 cytokine genes were upregulated including IL-1, IL-6, IL-8, IFN-$\gamma$, and TNF-$\alpha$. Taken together, the data suggest that Korean mistletoe lectin, in parallel with European mistletoe, has an ability to modulate human T cell function.

          • SCIESCOPUSKCI등재

            Effect of Charge Carrier Lipid on Skin Penetration, Retention, and Hair Growth of Topically Applied Finasteride-Containing Liposomes

            Lee,,Sang-Im,Nagayya-Sriraman,,Santhosh-Kumar,Shanmugam,,Srinivasan,Baskaran,,Rengarajan,Yong,,Chul-Soon,Yoon,,Sang-Kwon,Choi,,Han-Gon,Yoo,,Bong-Kyu The Korean Society of Applied Pharmacology 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.2

            The aim of this study was to investigate the effect of charge carrier lipid on the skin penetration, retention, and hair growth of topically applied finasteride-containing liposomes. Finasteride-containing liposomes were prepared by traditional thin film hydration method using Phospholipon$^{(R)}$ 85 G and cholesterol with or without charge carrier lipid (1,2 dimyristoyl-sn-glycero-3-phosphate or 1,2-dioleoyl-trimethylammonium-propane for anionic and cationic charge, respectively). Freshly prepared finasteride-containing liposome suspension was applied on the hairless mouse skin, and skin penetration and retention were measured using Keshary-Chien diffusion cell. Non-liposomal formulation (ethanol 10% solution containing 0.5 mg/ml of FNS) was also used as a control. The amount of finasteride in the diffusion cell and mouse skin was measured by HPLC. The hair growth was evaluated using depilated male C57BL/6N mice. Mean particle size of all finasteride-containing liposomes was less than a micron, and polydispersity index revealed size homogeneity. Skin penetration and retention studies showed that significantly less amount of finasteride was penetrated when applied as anionic liposome while more amount of the drug was retained. Specifically, in liposome prepared with 10% anionic charge carrier lipid, penetration was 12.99 ${\mu}g/cm^2$ while retention was 79.23 ${\mu}g/cm^2$ after 24 h of application. In hair growth study, finasteride-containing anionic liposomes showed moderate efficacy, but the efficacy was not found when applied as cationic liposomes. In conclusion, topical application of finasteride using anionic liposome formulation appears to be useful option for the treatment of androgenetic alopecia to avoid systemic side effects of the drug.

          • SCIESCOPUSKCI등재

            Clinical Pharmacology of Mycophenolic Acid as Immunosuppressant in Organ Transplaantation

            Kang,,Ju-Seop,Lee,,Joo-Won,Jhee,,Ok-Hwa,Om,,Ae-Son,Lee,,Min-Ho,Shaw,,Leslie,M. The Korean Society of Applied Pharmacology 2005 Biomolecules & Therapeutics(구 응용약물학회지) Vol.13 No.2

            Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

          • SCIESCOPUSKCI등재

            Single Nucleotide Polymorphism in Cytochrome P450 2E1 among Korean Patients on Warfarin Therapy

            Han,,Dong-Hoon,Lee,,Min-Jeon,Kim,,Jeong-Hee,Lee,,Suk-Hyang The Korean Society of Applied Pharmacology 2006 Biomolecules & Therapeutics(구 응용약물학회지) Vol.14 No.4

            This study was designed to assess the distribution of cytochrome P450 2E1 (CYP2E1) polymorphism among Korean patients on warfarin therapy. CYP2E1 polymorphism was analyzed at 5' flanking region of CYP2E1 gene using restriction fragment length polymorphism method. Patient characteristics including the measured internal normalized ratio (INR) were also evaluated. Based on the warfarin dose and the bleeding cases, the patients were grouped as the regular dose control, the regular dose bleeding, the low dose control, and the low dose bleeding. Total 96 patients were evaluated for both Pst I and Rsa I loci of the CYP2E1 gene and the results showed that both loci were tightly linked. Thirty-three patients(34.4%) were heterozygotes and 4 patients(4.2%) were homozygote. There was no significant difference in patient characteristics in the dose and bleeding case groups. CYP2E1 polymorphism showed a little difference among the groups but was not statistically significant, however, lower INR value was observed in homozygote genotype groups. It was also revealed that genotype allele frequencies of CYP2E1 in Korean was close to other Asian groups but was significantly different from other Caucasian and African-American populations.

          • SCIESCOPUSKCI등재

            Costunolide Induces Apoptosis via Modulation of Cyclin-Dependent Kinase in HL-60 Human Leukemia Cells

            Kim,,Dong-Hee,Choi,,Jung-Hye,Park,,Hee-Juhn,Park,,Jae-Hoon,Lee,,Kyung-Tae The Korean Society of Applied Pharmacology 2010 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.4

            Costunolide is an active compound isolated from the stem bark of Magnolia sieboldii, and is considered a potential therapeutic for the treatment of various cancers. In this study, we investigated the underlying mechanism whereby costunolide induces the apoptosis of human leukemia cells. Using apoptosis analysis and quantitative reverse transcription-polymerase chain reaction (RT-PCR) results obtained during this study show that costunolide is a potent inducer of apoptosis and that it is triggered due to the premature activation of Cdc2. $G_1$-synchronized cells, which cannot undergo mitosis, were found to be more sensitive to costunolide, and Cdc2 mRNA levels were increased by costunolide treatment. Furthermore, the Cdk inhibitors, olomucine and butyrolactone I, were found to suppress costunolide-induced apoptosis. In addition, the PKC activator TPA rescued cells from cell death by costunolide, and this was prevented by the PKC inhibitor staurosporin. The present study suggests that costunolide induces the apoptosis of HL-60 leukemic cells by modulating cyclin-dependent kinase Cdc2.

          • SCIESCOPUSKCI등재

            Anti-Stress Effects of Ginsenoside Rg<sub>3</sub>-Standardized Ginseng Extract in Restraint Stressed Animals

            Kim,,Chung-Soo,Jo,,Young-Jun,Park,,Se-Ho,Kim,,Hae-Jung,Han,,Jin-Yi,Hong,,Jin-Tae,Cheong,,Jae-Hoon,Oh,,Ki-Wan The Korean Society of Applied Pharmacology 2010 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.4

            We tested whether ginsenosides $Rg_3$-standardized ginseng extract (RGE) has anti-stress effects in restraint-stressed animals. RGE increased time spent in the open arms and open arm entries in the elevated plus-maze test. In addition, RGE blocked the reduction of center zone distance and stereotypes behaviors in the open-field test. RGE also increased head dips in stressed mice, indicating anxiolytic-like effects. Stress decreased movement distance and duration, burrowing, and rearing frequency but increased face washing and grooming. RGE significantly reversed burrowing and rearing activity in stressed mice. In addition, we measured sleep architecture in restraint stressed rats using EEG recorder. Stress increased rapid eye movement (REM) sleep, but total sleep and non-rapid eye movement (NREM) sleep were not changed. RGE did not affect sleep architecture in stressed rats. These behavioral experiments suggest that RGE has anti-stress effects in restraint-stressed animal models.

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