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( So Ri Kim ),( Yong Chul Lee ),( Dong Im Kim ),( Yang Keun Rhee ),( Heung Bum Lee ),( Seoung Ju Park ),( Chi Ryang Chung ),( Seung Yong Park ),( Mi Ran Kang ) 대한결핵 및 호흡기학회 2012 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.114 No.-
Oxidative stress is well known to be implicated in the development of asthma. The mitochondrial respiratory chain is a major site of intracellular reactive oxygen species (ROS) generation and, at the same time, an important target for the damaging effects of ROS. Mito-Tempo is a specific mitochondrial ROS inhibitor and it is known to be associated with opening of mi-tochondrial permeability transition pore and inhibition of cell necroptosis or apoptosis. However, there is little information on the protective effects of Mito-Tempo on the inflammatory airway disorders including bronchial asthma and its acute exacerbation. We investigate the effects of Mito-tempo on the allergic airway inflammation and hyperresponsiveness using the mice sensitized with OVA and LPS and then challenged with OVA (OVALPS-OVA mice). The OVALPS-OVA mice showed the typical features of neutrophilic asthma; increased airway inflammatory cells, the pathologic changes, the increased levels of Th2 cytokines in lungs of OVALPS-OVA mice, increased mitochondrial ROS generation, and increased bronchial hyperresponsiveness. Interestingly, we found that in OVALPS-OVA mice, Mito-Tempo, a novel mitochondrial targeting agent significantly reduced the increases in inflammatory cytokines, mitochondrial ROS generation, airway inflammation, and bron-chial hyperresponsiveness. These findings indicate that mitochondrial dysfunction including oxidative damage may be im-plicated in the pathogenesis of bronchial asthma and provide the therapeutic potential of a mitochondrial targeting agent, Mito-Tempo, for bronchial asthma.
Is Laparoscopy-assisted Radical Gastrectomy Safe in Patients with Child-Pugh Class A Cirrhosis?
Kang, Sin Jae,Jung, Mi Ran,Cheong, Oh,Park, Young Kyu,Kim, Ho Goon,Kim, Dong Yi,Kim, Hoi Won,Ryu, Seong Yeob The Korean Gastric Cancer Association 2013 Journal of gastric cancer Vol.13 No.4
Purpose: We investigated early postoperative morbidity and mortality in patients with liver cirrhosis who had undergone radical gastrectomy for gastric cancer. Materials and Methods: We retrospectively reviewed the medical records of 41 patients who underwent radical gastrectomy at the Chonnam National University Hwasun Hospital (Hwasun-gun, Korea) between August 2004 and June 2009. There were few patients with Child-Pugh class B or C; therefore, we restricted patient selection to those with Child-Pugh class A. Results: Postoperative complications were observed in 22 (53.7%) patients. The most common complications were ascites (46.3%), postoperative hemorrhage (22.0%) and wound infection (12.2%). Intra-abdominal abscess developed in one (2.4%) patient who had undergone open gastrectomy. Massive ascites occurred in 4 (9.8%) patients. Of the patients who underwent open gastrectomy, nine (21.9%) patients required blood transfusions as a result of postoperative hemorrhage. However, most of these patients had advanced gastric cancer. In contrast, most patients who underwent laparoscopic gastrectomy had early stage gastric cancer, and when the confounding effect from the different stages between the two groups was corrected statistically, no statistically significant difference was found. There was also no significant difference between open and laparoscopic gastrectomy in the occurrence rate of other postoperative complications such as ascites, wound infection, and intra-abdominal abscess. No postoperative mortality occurred. Conclusions: Laparoscopic gastrectomy is a feasible surgical procedure for patients with moderate hepatic dysfunction.
Anti-obesity effects of black ginseng extract in high fat diet-fed mice
Mi Ra Lee,Byung Chan Kim,Ran Kim,Hyun In Oh,Hyun Kyoung Kim,Kang Ju Choi,Chang Keun Sung 고려인삼학회 2013 Journal of Ginseng Research Vol.37 No.3
Black ginseng is produced by a repeated steaming process. The aim of this study was to investigate the anti-obesity effects of black ginseng ethanol extract (BG-EE) in high fat (HF) diet-fed mice. Two groups were fed either a normal control (NC) diet or a HF diet (45% kcal fat). The other three groups were given a HF diet supplemented with 1% BG-EE, 3% BG-EE, and 5% BG-EE for 12 wk. The anti-obesity effects of the BG-EE supplement on body weight, the development of fat mass, and lipid mechanisms were assessed in obese mice. HF-induced hyperlipidemia, fat accumulation in the liver, and white adipose tissues were reduced after BG-EE supplementation. Total fecal weight and the amount of fecal fat excretion also were increased after BG-EE supplementation. These results suggest that BG-EE may be useful to ameliorate HF-induced obesity through the strong inhibition of fat digestion.
Kang, Chan Woo,Jang, Kang Won,Sohn, Jinyoung,Kim, Sung-Moo,Pyo, Kyoung-Ho,Kim, Hwan,Yun, Mi Ran,Kang, Han Na,Kim, Hye Ryun,Lim, Sun Min,Moon, Yong Wha,Paik, Soonmyung,Kim, Dae Joon,Kim, Joo Hang,Cho, American Association for Cancer Research 2015 Molecular Cancer Therapeutics Vol.14 No.10
<P><I>RET</I> rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and PDGFR, in <I>RET</I>-rearranged LADC has not been reported. The aims of the study are to explore antitumor effects and mechanisms of acquired resistance of dovitinib in <I>RET</I>-rearranged LADC. Using structural modeling and <I>in vitro</I> analysis, we demonstrated that dovitinib induced cell-cycle arrest at G<SUB>0</SUB>–G<SUB>1</SUB> phase and apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in <I>RET</I>-rearranged LC-2/ad cells. Strong antitumor effect of dovitinib was observed in an LC-2/ad tumor xenograft model. To identify the acquired resistance mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations of dovitinib to generate LC-2/ad DR cells. Gene-set enrichment analysis of gene expression and phosphor-kinase revealed that Src, a central gene in focal adhesion, was activated in LC-2/ad DR cells. Saracatinib, an src kinase inhibitor, suppressed ERK1/2 phosphorylation and growth of LC-2/ad DR cells. Taken together, these findings suggest that dovitinib can be a potential therapeutic option for <I>RET</I>-rearranged LADC, in which acquired resistance to dovitinib can be overcome by targeting Src. <I>Mol Cancer Ther; 14(10); 2238–48. ©2015 AACR</I>.</P>
Kang, Woo Youl,Seong, Sook Jin,Ohk, Boram,Gwon, Mi-Ri,Kim, Bo Kyung,La, Sookie,Kim, Hyun-Ju,Cho, Seungil,Yoon, Young-Ran,Yang, Dong Heon,Lee, Hae Won Dove Medical Press 2018 Drug design, development and therapy Vol.12 No.-
<P><B>Purpose</B></P><P>A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance.</P><P><B>Methods</B></P><P>The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.</P><P><B>Results</B></P><P>Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C<SUB>max</SUB>) and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC<SUB>0–t</SUB>) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C<SUB>max</SUB> and AUC<SUB>0–t</SUB> values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C<SUB>max</SUB> and AUC<SUB>0–t</SUB> (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353–0.9846) and 0.9431 (0.8698–1.0226), respectively. The GMR and 90% CI for the S-amlodipine C<SUB>max</SUB> and AUC<SUB>0–t</SUB> (FDC/concomitant administration) were 0.9829 (0.9143–1.0567) and 0.9632 (0.8798–1.0546), respectively. As the intrasubject variability of the C<SUB>max</SUB> for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study.</P><P><B>Conclusion</B></P><P>CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments.</P>
( Mi Sun Kim ),( Tae Jun Park ),( Ji Youn Park ),( Hye Ran Kim ),( Sun Yi Park ),( Kyoung Chan Park ),( Jean Paul Ortonne ),( Hee Young Kang ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2
Background: Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Using a microarray analysis, hyperpigmentary skin of melasma expressed high levels of Wnt inhibitory factor-1 (WIF-1) compared to perilesional normal skin. Objectives: In this study, we investigated the expression and functional role of WIF-1 in melanocytes. Methods: The expressions and fuctions of WIF-1 were assessed by Immunohistochemical staining, RT-PCR, western blot analysis, and immunocytochemical staining. Using a lentivirus system, WIF-1 was overexpressed in normal human melanocytes. siRNA system was used for WIF-1 downregulation. Ex vivo skin organ culture and promoter analysis were performed. Results: WIF-1 was expressed in both the melanocytes of normal human skin and in cultured melanocytes. The upregulation of WIF-1 on cultured normal human melanocytes significantly induced expressions of MITF and tyrosinase, which were associated with increased melanin content and tyrosinase activity. Consistent with the stimulatory effect of WIF-1, WIF-1 siRNA reduced melanogenesis in the cells. Moreover, WIF-1 increases pigmentation in melanocytes co-cultured with WIF-1 overexpressed fibroblasts and of organ-cultured human skin. Conclusion: These findings suggest that melanocytes express WIF-1 constitutively in vivo and in vitro and that WIF-1 promotes melanogenesis in normal human melanocytes. WIF-1 may have a role of increased melanogenesis in melanocytes of melasma skin.
Kang, Woo Youl,Seong, Sook Jin,Ohk, Boram,Gwon, Mi-Ri,Kim, Bo Kyung,Cho, Seungil,Shim, Wang-Seob,Lee, Kyung-Tae,Kim, Eun Hee,Yang, Dong Heon,Lee, Hae Won,Yoon, Young-Ran Dove Medical Press 2018 Drug design, development and therapy Vol.12 No.-
<P><B>Purpose</B></P><P>A new fixed-dose combination (FDC) formulation of 120 mg fimasartan and 20 mg rosuvastatin was developed to increase therapeutic convenience and improve treatment compliance.</P><P><B>Methods</B></P><P>A randomized, open-label, single-dose, two-treatment, two-way crossover study with a 7-day washout period was conducted to compare the pharmacokinetic (PK) characteristics and bioequivalence between an FDC of fimasartan/rosuvastatin and the separate co-administration of fimasartan and rosuvastatin in healthy Korean volunteers. The plasma concentrations of fimasartan and rosuvastatin were analyzed by a validated liquid chromatography-tandem mass spectrometry method, for which serial blood samples were collected for up to 48 hours post-administration of fimasartan and 72 hours post-administration of rosuvastatin, in each period. The PK parameters were calculated using a non-compartmental method.</P><P><B>Results</B></P><P>A total of 78 subjects completed the study. All the 90% CIs of the geometric mean ratios (GMRs) fell within the predetermined acceptance range. The GMR and 90% CI for the area under the plasma concentration-time curve from time 0 to the last measurement (AUC<SUB>0–t</SUB>) and the maximum plasma concentration (C<SUB>max</SUB>) for fimasartan were 0.9999 (0.9391–1.0646) and 1.0399 (0.8665–1.2479), respectively. The GMR and 90% CI for the AUC<SUB>0–t</SUB> and C<SUB>max</SUB> for rosuvastatin were 1.0075 (0.9468–1.0722) and 1.0856 (0.9944–1.1852), respectively. Treatment with fimasartan and rosuvastatin was generally well tolerated without serious adverse events.</P><P><B>Conclusion</B></P><P>The new FDC formulation of 120 mg fimasartan and 20 mg rosuvastatin can be substituted for the separate co-administration of fimasartan and rosuvastatin, for the advantage of better compliance with convenient therapeutic administration.</P>
RFLP Analysis of cag7 Gene of Helicobacter pylori
Kang, Hyung-Lyun,Park, Jeong-Uck,Choe, Mi-Young,Kim, Kyung-Mi,Kim, Do-Su,Kwan, Young-Chul,Park, Seung-Gyu,Hwang, Hyang-Ran,Song, Jae-Young,Baik, Seung-Chul,Lee, Woo-Kon,Youn, Hee-Shang,Cho, Myung-Je The Korean Society for Microbiology 2004 Journal of Bacteriology and Virology Vol.34 No.3
The cag7 gene of Korean H. pylori strains was analyzed by RFLP to develop a discriminatory tool for genotyping clinical isolates. For this study, a total of 82 H. pylori strains were isolated from the patients; 27 strains from the patients with chronic gastritis, 26 from duodenal ulcer, and 29 from gastric cancer. Genomic DNA was isolated and subjected to PCR targeting entire ORF or the repeat regions I and II of cag7 gene. PCR products from entire ORF or repeat region I of cag7 gene were divided into two types. However, there was no difference in the length of PCR products from the repeat region II. By the PCR genotyping of the entire cag7 gene, genotypes A and B were established, which showed approximately 5,100 and 5,500 bp PCR products, respectively. The repeat region I showed approximately 600 or 1,000 bp DNA fragments by PCR. The length of cag7 gene was determined by the size variation in the repeat region I. In addition, RFLP analysis of the PCR products of cag7 gene showed 11 subtypes, based on the major bands. These findings illustrate that the genetic diversity of the repeat region I would serve a reliable target for the genotyping of the cag 7 gene.