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Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury
Won, A Jin,Kim, Siwon,Kim, Yoon Gyoon,Kim, Kyu-Bong,Choi, Wahn Soo,Kacew, Sam,Kim, Kyeong Seok,Jung, Jee H.,Lee, Byung Mu,Kim, Suhkmann,Kim, Hyung Sik The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.1
<P>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-alpha (GST-alpha), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.</P>
Kim, Se-Mi,Kim, Hwan-Ho,Shin, Sae-Byeok,Kang, Hyun-Ah,Cho, Hea-Young,Kim, Yoon-Gyoon,Lee, Yong-Bok The Korean Society of Pharmaceutical Sciences and 2007 Journal of Pharmaceutical Investigation Vol.37 No.5
The purpose of the present study was to evaluate the bioequivalence of two lercanidipine hydrochloride tablets, Zanidip tablet (LG Life Sciences Ltd., Korea, reference drug) and Samchundang Lercanidipine tablet 10 mg (Sam Chun Dang Pharm. Co. Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (amlodipine maleate) to human serum, serum samples were extracted using hexan-isoamyl alcohol (100:1, v/v). Compounds were analyzed by liquid chromatography/tandem mass spectrometry. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL which was sensitive enough for pharmacokinetic studies. Thirty healthy male Korean volunteers received each medicine at the lercanidipine hydrochloride dose of 20 mg in a $2\;{\times}\;2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of lercanidipine were monitored by an LC/MS/MS fer over a period of 24 hr after the administration. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters, indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Samchundang Lercanidipine/Zanidip were log 0.9505-log 1.2258 and log 0.9987-log 1.2013, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Samchundang Lercanidipine tablet 10 mg and Zanidip tablet are bioequivalent.
Antioxidative effects of quercetin-glycosides isolated from the flower buds of Tussilago farfara L.
Kim, Mi-Ran,Lee, Jeong Yong,Lee, Hyang-Hee,Aryal, Dipendra Kuma,Kim, Yoon Gyoon,Kim, Sang Kyum,Woo, Eun-Rhan,Kang, Keon Wook 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10
A bioassay-guided fractionation of the ethylacetate soluble fraction from the flower buds of Tussilago farfara L. (Compositae) yielded two flavonoids, quercetin 3-O-β-L-arabinopyranoside and quercetin 3-O-β-D-glucopyranoside. These two sugar conjugates of quercetin exhibited higher antioxidative activity than their aglycone, quercetin by NBT superoxide scavenging assay. Moreover, treatment with quercetin 3-O-β-L-arabinopyranoside significantly increased the total glutathione (GSH) contents and the protein level of γ-glutarnylcysteine ligase (γ-GCL), a key enzyme required for glutathione (GSH) synthesis in a rat hepatocyte cell line. Subcellular fractionation and reporter gene analysis using antioxidant response element (ARE) construct revealed that quercetin 3-O-β-L-arabinopyranoside increased the level of nuclear Nrf2 and reporter activity, and that these were associated with the induction of the γ-GCL gene. After 24 h incubation of cells with quercetin 3-O-β-L-arabinopyranoside, 23% of the glycoside was converted to its aglycone, quercetin, but γ-GCL was not induced by 7 μM (23%) quercetin. These results suggest that the two quercetin-glycosides isolated from T. farfara L. have direct antioxidative properties, and that quercetin 3-O-β-L-arabinopyranoside increases the cellular GSH level by inducing the γ-GCL gene. These novel effects of quercetin-glycosides are suggestive to underlie the potential putative chemopreventive effects of T.farfara L.
Kim, In-Wha,Moon, Yoo Jin,Ji, Eunhee,Kim, Kyung Im,Han, Nayoung,Kim, Sung Ju,Shin, Wan Gyoon,Ha, Jongwon,Yoon, Jeong-Hyun,Lee, Hye Suk,Oh, Jung Mi Springer-Verlag 2012 European journal of clinical pharmacology Vol.68 No.5
<P>The purpose of this study was to characterize the effects of clinical and genetic variables on the pharmacokinetics and complications of tacrolimus during the first year after kidney transplantation. One hundred and thirty-two Korean kidney recipients who received tacrolimus were genotyped for ABCB1 (exons 12, 21, and 26) and CYP3A5 (intron 3). Tacrolimus trough levels, dose, or dose-adjusted trough levels and complications were compared among patients during the early stage (3, 7, 14, 30, and 90 days) and up to 1 year according to the genotypes. A donor source-adjusted linear mixed model with multilevel analysis adjusting for age, body weight, hematocrit, and serum creatinine showed that CYP3A5 genotype is associated with dose-adjusted level of tacrolimus (p < 0.001). The influence of ABCB1 polymorphisms on the pharmacokinetics or complications of tacrolimus was less certain in our study. The incidence of acute rejections was significantly higher in recipients of cadaveric donor kidney (p < 0.05). A generalized estimating equation model analysis showed that alopecia and hyperlipidemia were associated with dose-adjusted level of tacrolimus (p < 0.001). Genotype of CYP3A5 variants along with significant clinical covariates may be useful in individualizing tacrolimus therapy in kidney transplantation patients.</P>
Inhibition of Human Ovarian Tumor Growth by Cytokine-induced Killer Cells
Kim, Hwan-Mook,Kang, Jong-Soon,Lim, Jae-Seung,Park, Song-Kyu,Lee, Ki-Ho,Yoon, Yeo-Dae,Lee, Chang-Woo,Lee, Ki-Hoon,Han, Gyoon-Hee,Yang, Kyu-Hwan,Kim, Yeon-Jin,Kim, Young-Soo,Han, Sang-Bae 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11
Despite the recent improvement in the treatment of ovarian cancer, this disease is still leading cause of cancer death in women. In this study, the anti-tumor activity of cytokine-induced killer (CIK) cells against human ovarian cancer was evaluated in vitro and in vivo. Although $CD3^+CD56^+$ cells were rare in fresh human peripheral blood mononuclear cells, they could expand more than 1,000-fold on day 14 in the presence of anti-CD3 antibody plus IL-2. At an effector-target cell ratio of 30:1, CIK cells destroyed 45% of SK-OV-3 human ovarian cancer cells, which was determined by the $^{51}Cr-release$ assay. In addition, CIK cells at a dose of 23 million cells per mouse inhibited 73% of SK-OV-3 tumor growth in nude mouse xenograft assay. This study suggests that CIK cells may be used as an adoptive immunotherapy for patients with ovarian cancer.
Remote Position Detection of Steel Coils Using 2D Laser Scanners : Two-line-tracker
Yonghun Kim,Pyungkang Kim,Kyeongyong Cho,Yoon-Shik Hong,Soohyun Kim,Kyung-Soo Kim,Young-Keun Kim,Tae-Gyoon Lim 제어로봇시스템학회 2014 제어로봇시스템학회 국제학술대회 논문집 Vol.2014 No.10
It is important to measure the position of steel coils, especially when automatically transporting them by crane in the relevant industry. To realize a fully automatic coil transporting system, the positions of coils relative to the crane must be measured accurately. This paper introduces a measurement system that can detect positions of the target coil with high robustness and accuracy using 2-D laser sensors. The proposed system can derive the radius, length of a coil, which can be in various sizes, without using any prior informations about the coil. Based on the detected dimensions of the target coil, the sensor system can calculate the positions of coil in real time from a remote distance. The performance of the system is validated through experiments conducted on actual coils, which showed that the precision is within 30mm from a distance range of 5 meters.