In Sook Kim

Hanyang University, Sŏul, Seoul, South Korea

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Publications (56)141.99 Total impact

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    ABSTRACT: This study investigated the effects of intestinal microbiota on the metabolism of geniposide by using a rat model treated with a mixture of antibiotics. The plasma concentration of geniposide was determined after oral administration in control and antibiotics-treated rats by using liquid chromatography-tandem mass spectrometry. The maximum plasma concentrations (Cmax) of geniposide in control and antibiotics-treated rats were 0.91 ± 0.26 and 1.01 ± 0.04 μg/mL, respectively, and the area under the curve (AUC) values were 7.34 ± 3.32 and 11.9 ± 2.1 μg·h/mL (p < 0.05), respectively. The levels of geniposide in rat feces were 0.64 and 15.6 mg, respectively, in the control and antibiotics-treated groups. Thus, the systemic exposure of geniposide was greater in the antibiotics-treated rats. This may be due to the antibiotic-induced suppression of the metabolic activities of the intestinal microbiota. These results suggest that the gut microbiota may have an impact on the bioavailability of geniposide.
    Journal of agricultural and food chemistry. 09/2014;
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    ABSTRACT: Orally-administered drugs may be metabolized by intestinal microbial enzymes before absorption into the blood. Accordingly, co-administration of drugs affecting the metabolic activities of gut microbes (e.g. antibiotics) may lead to drug-drug interactions (DDI). In this study, gut microbiota-mediated DDI were investigated by studying the pharmacokinetics of lovastatin in antibiotic-treated rats. Incubation of lovastatin with human and rat fecalase preparations produced four metabolites, M1 (demethylbutyryl metabolite), M4 (hydroxylated metabolite), M8 (the active hydroxy acid metabolite), and M9 (hydroxylated M8) indicating involvement of the gut microbiota in lovastatin metabolism. The plasma concentration-time profiles of M8 were compared after oral administration of lovastatin to control rats or those treated with either ampicillin (100 mg/kg), or an antibiotic mixture consisting of cefadroxil (150 mg/kg), oxytetracycline (300 mg/kg), and erythromycin (300 mg/kg). Pharmacokinetic analyses indicated that systemic exposure to M8 was significantly lower in antibiotic-treated rats, as compared with controls. In addition, fecal M8 formation decreased by 58.3% and 59.9% in the ampicillin- and antibiotic mixture-treated rats, respectively. These results suggested that antibiotic intake may reduce the biotransformation of orally-administered drugs by gut microbiota and that the subsequent decrease of drug absorption could induce pharmacokinetic drug interactions.
    Drug metabolism and disposition: the biological fate of chemicals 06/2014; · 3.74 Impact Factor
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    ABSTRACT: Abstract 1. The absorption, distribution, metabolism and excretion of a novel dipeptidyl peptidase IV inhibitor, gemigliptin, were examined following single oral administration of (14)C-labeled gemigliptin to rats. 2. The (14)C-labeled gemigliptin was rapidly absorbed after oral administration, and its bioavailability was 95.2% (by total radioactivity). Distribution to specific tissues other than the digestive organs was not observed. Within 7 days after oral administration, 43.6% of the administered dose was excreted via urine and 41.2% was excreted via feces. Biliary excretion of the radioactivity was about 17.7% for the first 24 h. After oral administration of gemigliptin to rats, the in vivo metabolism of gemigliptin was investigated with bile, urine, feces, plasma and liver samples. 3. The major metabolic pathway was hydroxylation, and the major circulating metabolites were a dehydrated metabolite (LC15-0516) and hydroxylated metabolites (LC15-0635 and LC15-0636).
    Xenobiotica 04/2014; · 1.98 Impact Factor
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    ABSTRACT: Aromatase (CYP 19A1) is a key steroidogenic enzyme that catalyzes the conversion of androgen to estrogen. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for aromatase inhibitor screening was developed and validated. The substrate androstenedione was incubated with human CYP 19A1 supersomes in the presence of NADPH for 30 min, and estrone formation was determined by LC-MS/MS analysis. Cortisone was used as internal standard. The incubation mixture was extracted using a liquid-liquid extraction method with ethyl acetate. Chromatographic separation was achieved using a C18 column (3.0 × 50 mm, 2.7 μm) with a mobile phase consisting of 0.1 % formic acid/acetonitrile adopting gradient elution at a flow rate of 0.4 mL/min. The mass spectrometer was operated in positive electrospray ionization mode. The precursor-product ion pairs used for multiple reaction monitoring were m/z 287→97 (androstenedione), m/z 271 → 159 (estrone), and m/z 361 → 163 (IS, cortisone). The developed method met the required criteria for the validation of bioanalytical methods. The validated method was successfully applied to evaluate aromatase inhibitory activity of plants extracts of Simaroubaceae.
    Analytical and Bioanalytical Chemistry 04/2014; · 3.66 Impact Factor
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    ABSTRACT: Functional activation of stem cells after transplantation is a main concern in stem cell therapy. For local transplantation, mesenchymal stem cells (MSCs) are usually administered via scaffolds, either by direct implantation or after pre-culturing of cells, and it is unclear which is better for the activation of transplanted cells. In this study, we investigated the in vivo gene expression activity of human MSCs (hMSCs) transplanted into calvarial defects either directly post-seeding on collagen sponges (Group 1) or after overnight in vitro culturing post-seeding (Group 2). Real-time RT-PCR at days 7 and 14 after transplantation identified a time-dependent, rapid decrease in gene expression by the hMSCs, which in Group 1 was slightly more attenuated than in Group 2. Both groups exhibited a limited range of human-specific gene expression, which involved type I collagen (ColI), fibronectin, SDF-1 and osteoprotegerin. Among these, ColI expression was the most efficient, with higher levels in Group 1 than Group 2. There was a lack of evidence for the expression of osteoblast differentiation-related markers or trophic factors, while resident cells showed clear expression of those genes. Rat-specific β-actin expression in Group 2 was least among the scaffold control, Group 1 and Group 2, and this pattern was repeated in the expression of other rat osteogenic genes. Group 1 transplants positively influenced the osteogenic process of the defect tissue in part, and rat IGF-1 expression was significantly increased in Group 1. This tendency of gene expression by hMSCs in a rat model was very similar to what was observed in transplantations using immunodeficient mice. The current study showed that a main gene expressed by transplanted hMSCs during the initial weeks following transplantation is ColI, with a lack of differentiation-related markers or growth factor expression by hMSCs. Our data suggest that direct transplantation of hMSCs loaded on a collagen sponge is more efficient for gene activation in transplanted hMSCs, and more favorable to the local host tissue than transplantation after pre-culturing of cells.
    Tissue Engineering Part A 02/2014; · 4.64 Impact Factor
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    ABSTRACT: Rhus verniciflua Stokes has been used as a traditional herbal medicine in Asia. In this study, the effect of R. verniciflua extract on human aromatase (cytochrome P450 19, CYP19) activity was investigated to elucidate the mechanism for the effect of R. verniciflua extract on androgen hormone levels. Androstenedione was used as a substrate and incubated with R. verniciflua extract in cDNA-expressed CYP19 supersomes in the presence of NADPH, and estrone formation was measured using liquid chromatography-tandem mass spectrometry. R. verniciflua extract was assessed at concentrations of 10-1000μg/mL. The resulting data showed that R. verniciflua extract inhibited CYP19-mediated estrone formation in a concentration-dependent manner with an IC50 value of 136μg/mL. Subsequently, polyphenolic compounds from R. verniciflua extract were tested to identify the ingredients responsible for the aromatase inhibitory effects by R. verniciflua extract. As a result, butin showed aromatase inhibitory effect in a concentration-dependent manner with an IC50 value of 9.6μM, whereas the inhibition by other compounds was negligible. These results suggest that R. verniciflua extract could modulate androgen hormone levels via the inhibition of CYP19 activity and butin is a major ingredient responsible for this activity.
    Bioorganic & medicinal chemistry letters 02/2014; · 2.65 Impact Factor
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    ABSTRACT: A simple, sensitive, and precise reversed-phase liquid chromatographic method was developed for the quantitative determination of 4 bioactive phenolic compounds (gallic acid, fustin, fisetin, and sulfuretin) from the stem extract of Rhus verniciflua stokes. Chromatographic analysis was performed on a Capcell Pak C18 column (150×4.6mm, 3μm) with a mobile phase consisting of 0.1% formic acid and 90% acetonitrile at a flow rate of 1mL/min. Quantitation was performed using a UV-vis detector at 260nm. The method was validated in terms of selectivity, linearity, accuracy, precision, and recovery. Excellent linear behavior was observed over the investigated concentration range (10-500μg/mL for gallic acid, fustin, and fisetin; 0.5-100μg/mL for sulfuretin) with correlation coefficient (r(2)) values >0.99. The intra- and inter-day precision over the concentration range of compounds was less than 6.65% (relative standard deviation) and the accuracy was between 92.42% and 103.62%. The mean recoveries for all the analytes were more than 92.18%. This method was successfully applied for the analysis of bioactive phenolic compounds in the R. verniciflua extracts.
    Food Chemistry 12/2013; 141(4):3813-9. · 3.33 Impact Factor
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    ABSTRACT: While recombinant human bone morphogenetic protein (rhBMP)-2-based bone therapy presents potential osteoinductivity, it also leads concern due to transient osteoclast activation during early healing periods, ultimately limiting its clinical use. Therefore, we investigated in vivo and in vitro rhBMP-2 signaling which mediates early bone resorbing effect, depending on the dose, and attempted to inhibit this resorption phenomenon using NFAT inhibitor as a target molecule. High-dose of rhBMP-2 (20 μg/defect) enhanced osteoclast activation and the expression of bone resorption markers, compared to low dose (5 μg/defect) at one week after surgery in collagen sponge-delivered rat calvarial defect models. Interestingly, this trend was also observed in the expression of bone formation markers. In particular, rhBMP-2 upregulated RANKL expression, while it downregulated osteoprotegerin (OPG) expression, resulting in a dose-dependent increase in the ratio of RANKL to OPG. NFAT inhibitor (150 μm) treatment in vivo suppressed the high-dose effect of rhBMP-2 on both resorption and formation. In vitro results of rhBMP-2 signaling and NFAT inhibitor effects in rat mesenchymal stem cells showed similar trends as in vivo results. Microcomputer tomography-based evaluation at 4 weeks showed that combined treatment of NFAT inhibitor with 20 μg rhBMP-2 in vivo increased bone volume (BV) more than 20 μg rhBMP-2 alone, which showed little difference in BV compared to 5 μg of rhBMP-2. These results demonstrated that rhBMP-2 implantation concurrently signalized into enhanced osteoclastogenesis and osteoblastogenesis in vivo, dose-dependently. Ratio of RANKL/OPG might be an index for early bone resorbing activity of implanted rhBMP-2. A local cocktail treatment of NFAT inhibitor and high-dose rhBMP-2 might be an alternative to overcome early bone resorbing effects, thereby accelerating bone formation.
    Biomaterials 12/2013; · 8.31 Impact Factor
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    ABSTRACT: High-power pulsed lasers have been recently regarded to be anabolic to bone, but in vivo evidence is still lacking. This study aimed to investigate the capacity of bone repair using a high-power, Q-switched, pulsed, neodymium-doped yttrium aluminium garnet (Nd:YAG) laser, using bilateral calvarial defect models having non-critical sized, 5 mm (rat) or 8 mm (rabbit) diameter. One of the bilateral defects, which were all filled with collagen sponge or left empty, was irradiated with a Nd:YAG laser once every 2 days for 2 weeks at a constant total fluence rate (344 J/cm(2) ), output power (0.75 W), pulse repetition rate (15 pps) and wavelength (1064 nm) and examined for the laser effect. The same experimental scheme was designed using a rabbit calvarial defect model implanted with sponge, which was explored for the dose effect of output power at 0.75 and 3 W with the same quantities of the other parameters. New bone formation was evaluated by micro-computed tomography-based analysis and histological observation at 4 weeks after surgery. Laser irradiation significantly increased new bone formation by approximately 45%, not only in the sponge-filled defects of rats but also when the defects were left empty, compared to the non-irradiated group. Consistently, both doses of output power (0.75 and 3 W) enhanced new bone formation, but there was no significant difference between the two doses. This study is one of the first to demonstrate the beneficial effect of Nd:YAG lasers on the regeneration of bone defects which were left empty or filled with collagen sponge, suggesting its great potential in postoperative treatment targeting local bone healing. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 11/2013; · 4.43 Impact Factor
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    ABSTRACT: We evaluated the new bone regeneration of a rabbit mandibular defect using hBMSCs under electrical stimulation combined with rhBMP-2 in this study. An inner scaffold prepared by setting a collagen sponge with hBMSCs and hydrogel was placed into a polycaprolactone (PCL) outer box, and an electrical stimulation device was installed between the inner scaffold and the outer box. There were three experimental groups depending on electrical stimulation and application of rhBMP-2. The experimental group was divided into the following three groups. Group 1, in which rhBMP-2 (5 μg/defect) was added to hydrogel and electrical stimulation was not applied; Group 2, in which rhBMP-2 (5 μg/defect) was added as in Group 1 and electrical stimulation was applied; and Group 3, in which electrical stimulation was applied and rhBMP-2 (5 μg/defect) was injected directly into defect site. The delivered electrical stimulation was charge-balanced bi-phasic electric current pulses, and electrical stimulation was conducted for 7 days. The stimulation parameters of the bi-phasic electrical current set at an amplitude of 20 μA, a duration of 100 μs and a frequency of 100 Hz. Four weeks after surgery, new bone formation in each group was evaluated using radiography, histology, and micro-computed tomography (μCT). Groups 2 and 3 exhibited a significant increase in new bone formation compared to Group 1, while Group 3 showed the highest level of new bone regeneration. In a comparison between two groups, Group 2 showed a higher bone volume (BV) by 260 % (p < 0.01) compared with Group 1, and Group 3 showed a higher BV by 442 % (p < 0.01) compared with Group 1. The trend of the bone surface density (ratio of new bone to the real defect volume, BS/TV), trabecular number, and connectivity was identical to that of the BV. The total bone mineral density (BMD) of Groups 2 and 3 showed values higher by the ratios of 103 % (p < 0.01) and 107.5 % (p < 0.01) compared with Group 1, respectively. Part BMD for Groups 2 and 3 showed higher values by the ratios of 104.9 % (p < 0.01) and 122.4 % (p < 0.01) compared with Group 1, respectively. These results suggest that the combined treatment of electrical stimulation, hBMSCs, a collagen sponge, hydrogel, and rhBMP-2 was effective for bone regeneration of large-size mandibular defects. The application of rhBMP-2 with an injection following electrical stimulation demonstrated better efficiency as regards bone regeneration.
    Medical & Biological Engineering 08/2013; · 1.76 Impact Factor
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    ABSTRACT: This study aimed to assess the potential inhibitory effects of β-lapachone, a new anticancer candidate, on the activities of the cytochrome P450 (CYP450) enzymes in vitro. Different concentrations of β-lapachone were incubated with human liver microsomes in the presence of CYP isozyme-specific substrates and NADPH, and the formation of the marker metabolites was measured using liquid chromatography-tandem mass spectrometry. In addition, time-dependent inhibition was examined to characterize the mode of the inhibition. β-Lapachone showed concentration-dependent inhibitory effects on all CYP isozymes tested (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYPC19, CYP2D6, and CYP3A4), and its half-maximal inhibitory concentration (IC50) values ranged from 2.6 to 9.7 μM. However, β-lapachone did not appear to modulate CYP450 activities as a mechanism-based inactivator. These results suggest that pharmacological drug-drug interactions might occur between β-lapachone and drugs co-administered with it, which are extensively metabolized by CYP450 enzymes, and thus, careful observation is required in clinical pharmacokinetic studies.
    Cancer Chemotherapy and Pharmacology 07/2013; · 2.80 Impact Factor
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    ABSTRACT: β-Lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione) is a natural compound extracted from the bark of the lapacho tree (Tabebuia avellanedae) and is undergoing phase II clinical trials as an antitumor drug candidate. The present study characterized in vitro metabolites of β-lapachone in mouse, rat, dog, monkey and human liver microsomes. β-Lapachone (10μM) was incubated with mouse, rat, dog, monkey, and human liver microsomes in the presence of NADPH. The reaction mixtures were analyzed by LC/MS and the metabolites were identified based on their elemental composition and product ion spectra. A total of 6 metabolites (M1-M6) were detected in liver microsomes with a slight difference between species. M1 and M6 were identified as a decarbonated metabolite and a carboxylated metabolite, respectively; M2, M3, and M4 were identified as monohydroxylated metabolites; and M5 was identified as an O-methylated metabolite. M5, an O-methylated metabolite was found in rat and human liver microsomes, which is thought to be formed from a catechol intermediate by MB-COMT-mediated methylation and reported here for the first time.
    Journal of pharmaceutical and biomedical analysis 05/2013; 83C:286-292. · 2.45 Impact Factor
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    ABSTRACT: In this study, we describe and validate a rapid and sensitive method for quantitation of dapoxetine in rat plasma by using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS). Plasma samples were prepared by protein precipitation with acetonitrile, and sildenafil was used as an internal standard (IS). The mobile phase consisted of 0.5% formic acid/acetonitrile (60:40, v/v); a C18 reversed-phase column (2.0×50mm, 1.7μm) was used for chromatographic separation. Multiple reaction monitoring (MRM) was used in the positive ion mode for mass spectrometric detection. The calibration curve for dapoxetine was linear (r(2)=0.999) in the concentration range of 1-500ng/mL. The intra- and inter-day precision was between 3.8% and 8.3%, and the intra- and inter-day accuracy was between 101.1% and 109.0%. Dapoxetine was found to be stable in various conditions with the recoveries>87.0% (RSD <7.2%). The method was found to be specific, precise, and accurate, and no matrix effect was observed. Our results suggest that this method can be successfully applied in pharmacokinetic studies of dapoxetine in rat plasma.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 03/2013; 926C:42-46. · 2.78 Impact Factor
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    ABSTRACT: In the present study, the effect of CP-001, a standardized herbal mixture of Houttuynia cordata, Rehmannia glutinosa, Betula platyphylla, and Rubus coreanus, on cytochrome P450 (CYP) enzyme-mediated drug metabolism was investigated in vitro to evaluate the potential for herb-drug interactions. CP-001 was tested at concentrations of 1, 3, 10, 30, and 100 μ g/mL. A CYP-specific substrate mixture was incubated with CP-001 in human liver microsomes, and the metabolites generated by each CYP-specific metabolic reaction were measured by liquid chromatography-tandem mass spectrometry. CP-001 seemed to slightly inhibit some CYP isozymes, but the IC50 values for all CYP isozymes were greater than 100 μ g/mL. Furthermore, CP-001 did not exhibit time-dependent CYP inhibitory activities, indicating that it does not act as a mechanism-based inactivator of CYP enzymes. In conclusion, the effects of CP-001 on CYP isozyme activities were negligible at the concentrations tested. Therefore, the likelihood of herbal mixture-drug interaction is considered minimal.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:824270. · 1.72 Impact Factor
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    ABSTRACT: Purpose: Maxilla and mandible have different patterns of cortical and trabecular bone and different bone mineral densities, even though both are components of the jaw bone. However, cellular differences between maxilla- and mandible derived osteoblasts (OBs) have rarely been studied. We hypothesize that maxilla- and mandible-derived OBs show different responses to -estradiol (E2), which is one of the critical factors for bone formation. This study compares skeletal site-specific cell responses between maxilla- and mandible-derived human OBs to E2. Methods: Maxilla- and mandible-derived OBs derived from an identical donor were separately isolated from a total of five normal healthy subjects aged 18~44 years old, cultured with a treatment of 100 nM estrogen. The responses between maxilla- and mandible-derived OBs to E2 were evaluated and compared using cell proliferation, alkaline phosphatase (ALP) activity and gene expression of osteoprotegerin (OPG), ALP, insulin-like growth factor-1 (IGF-1), and estrogen receptor (). Results: E2 did not have any distinct effects on the proliferation of both types of OBs. Mandible-derived OBs exhibited higher ALP activity than maxilla-derived OBs in the non-treated condition, which was common in all tested individuals. ALP activities of both types of OBs showed a minor increasing tendency with the treatment of E2, even though there was no statistical significance in some specimens. The gene expression of OB by E2 was diverse, depending on the individuals. There was increased expression of OPG, IGF-1, or gene in the part of subjects, which was more repeated in maxilla-derived OBs. In particular, OPG or ALP induction by E appeared less frequently in mandible-derived OBs. Conclusion: Current results revealed that E2 affects maxilla- and mandible-derived OBs into facilitating the osteogenic process despite individual differences. Mandible-derived OBs are less sensitive to bone-forming gene expression by E2.
    Maxillofacial Plastic and Reconstructive Surgery. 01/2013; 35(1).
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    ABSTRACT: Geniposide is a biologically active ingredient of gardenia fruit. A liquid chromatography-tandem mass spectrometric method was developed and validated for the determination of geniposide in rat plasma. The plasma samples were pretreated by solid-phase extraction and introduced into a BDS Hypersil column (, ) for chromatographic separation. The mobile phase consisted of 0.1% formic acid and 0.1% formic acid in acetonitrile, and gradient elution was performed at a flow rate of 0.25 mL/min. For mass spectrometric detection, multiple reaction monitoring was performed via an electrospray ionization source in positive mode. The calibration curve for geniposide was linear () in the concentration range of . The intra- and inter-day accuracies and precisions fulfilled the required criteria (). The developed method was subsequently used for pharmacokinetic analysis of geniposide after oral administration to rats at a dose of 50 mg/kg. The mean maximum plasma concentration of geniposide was at , and the mean area under the plasma concentration versus time curve was .
    Bulletin- Korean Chemical Society 01/2013; 34(9). · 0.84 Impact Factor
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    ABSTRACT: Ex-vivo expanded mesenchymal stromal cells (MSCs) represent a potential cell population for tissue regeneration strategy. Xenogeneic transplantation using human MSCs (hMSCs) can be an approach to reveal what hMSCs guide in bone regeneration with distinguishable gene expression from host animal. In this study, we investigated the regenerating effect of hMSCsvarying injection time point in rabbit distraction osteogenesis (DO) model. Undifferentiated hMSCs (2 x 106 cells) were injected transcutaneously into the osteotomy site of one side of the mandible one day prior to onset of distraction (Group 1) or after distraction (Group 2). The contralateral side of the mandible, which was subjected to distraction but no hMSC injection, was used as the control in each group. hMSCs showed lack of major histocompatibility complex class II expression and suppression of xenogeneic lymphocyte proliferation stimulated by proinflammatory cytokine. Micro-computed tomography-based evaluation showed a significant increase in new bone volume in the distracted callus in Group 1 compared to the contralateral side. Injection of hMSCs increased the bone mineral density (BMD) of the regenerated bone in both Group 1 and 2, although the former had a higher BMD than the latter. hMSCs of Group 1 subjected to distraction after injection expressed IGF-1 and fibronectin, while the expression of most osteoblast differentiation-related markers and growth factors was negligible. These results demonstrated that hMSCs exerted immune suppressive behavior in rabbit T cells in vitro, and hMSC transplantation into the distracted callus of a rabbit model provided osteogenic benefits that were more pronounced when the hMSCs were injected just prior to distraction than at the end of distraction. The beneficial effect of hMSCs might be mediated, partly by the expression of matrix proteins or IGF-1 which are known to favor bone formation.
    Tissue Engineering Part A 10/2012; · 4.64 Impact Factor
  • Tae Kon Kim, In Sook Kim, Hye Hyun Yoo
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    ABSTRACT: In this study, a sensitive, simple and reliable method for the quantification of docetaxel in rat plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The plasma samples were prepared by protein precipitation, and paclitaxel was used as an internal standard (IS). Chromatographic separation was achieved using a Gemini C(18) column (2.0 × 150 mm, 5 µm) with a mobile phase consisting of 0.1% formic acid-acetonitrile (30:70, v/v). The precursor-product ion pairs used for multiple reaction monitoring were m/z 808.5 → 527.5 (docetaxel) and m/z 854.2 → 286.5 (IS, paclitaxel). A calibration curve for docetaxel was constructed over the range 1-1000 ng/mL. The developed method was specific, precise and accurate, and no matrix effect was observed. The validated method was applied in a comparative pharmacokinetic study in which two docetaxel formulations, SID530, a new parenteral formulation of docetaxel with hydroxypropyl-β-cyclodextrin (HP-β-CD), and Taxotere, were administered to rats at a dose of 5 mg/kg. For SID530 and Taxotere, the mean C(0) values were 1494 and 1818 ng/mL, respectively, and the AUC(last) values were 837 and 755 h ng/mL, respectively. These two formulations did not show any statistical differences with regard to the pharmacokinetic parameters, thus establishing that the SID530 and Taxotere products are pharmacokinetically comparable in male rats. Copyright © 2012 John Wiley & Sons, Ltd.
    Biomedical Chromatography 07/2012; · 1.95 Impact Factor
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    ABSTRACT: This study investigates the hypothesis that the ethyl acetate extract of rice fermented with red yeast (Monascuspilosus) in medium containing garlic (RYRGE) inhibits the differentiation of 3T3-L1 preadipocytes by down regulating cellular induction of PPARγ, and C/EBPα. Mouse 3T3-L1 preadipocytes were treated with 0.0, 0.125, and 0.25 mg/mL of RYRGE, and Oil Red O staining, triglyceride accumulation and glyceradehyde-3-phosphate dehydrogenase (GPDH) activity were measured as markers of adipocyte differentiation. The protein and mRNA expressions of PPARγ and C/EBPα were measured using Western Blot and RT-PCR, respectively. The mRNA expressions of leptin and aP2 genes were measured using RT-PCR. RYRGE significantly inhibited lipid accumulation and GPDH activity in dose-dependent manner (p<0.05). The mRNA and protein expressions of PPARγ and C/EBPα were dose-dependently inhibited by RYRGE. Similarly, RYRGE decreased the gene expression of adipocyte fatty acid binding protein (aP2) and leptin in a dose-dependent manner (p<0.05), which generally acts as an adipogenic marker proteins and C/EBPα and PPARγ target genes. These results indicate that RYRGE effectively attenuated adipogenesis by down-regulating the expression of adipocyte transcription factors and related adipogenic gene expressions.
    European Journal of Lipid Science and Technology 05/2012; 114(5). · 2.27 Impact Factor
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    ABSTRACT: Earlier, we demonstrated that local electrical stimulation (ES) improved bone and peripheral nerve regeneration. To determine how ES induces the regeneration of different kinds of tissues, we studied the initial ES-induced regeneration process by investigating the expression of chemokines and growth factors from human mesenchymal stromal cells (hMSCs). In particular, we assessed the responses of hMSCs grown in three-dimensional (3D) culture on a collagen sponge, as 3D culture techniques induced cell behavior that was similar to in vivo cell behavior. We also compared the gene expression patterns of monolayer hMSCs with those of 3D hMSCs under the condition that cells in either culture are exposed to the same type of ES. Biphasic pulses did not affect the proliferation of hMSCs in 3D culture significantly at the magnitude applied in previous animal studies showing improved bone and peripheral nerve regeneration. However, ES enhanced the gene expression of growth factors (BMP-2, IGF-1, and VEGF), chemokines (CXCL2, interleukin (IL)-8), and chemokine receptors (CXCR4 and IL-8RB) from hMSCs grown in 3D culture. A particular difference between the 3D and monolayer cultures was found in the expression of chemokine receptors, CXCR4 and IL-8RB, which is related to the homing capabilities of mesenchymal stromal cells. These genes were expressed by cells in 3D cultures, but were not or expressed at extremely low levels by cells grown in monolayer cultures. ES led to a significant increase in the expression of CXCR4 and IL-8RB in both monolayer and 3D hMSCs, but the increase in the monolayer culture was detected at an extremely low level. These results demonstrate that ES increased the expression of a variety of growth factors and chemokine genes from 3D hMSCs, which may explain increased tissue regeneration in vivo, independent of the tissue type. A culture-dependent expression of the CXCR4 gene suggested that cell response to external stimulus in 3D systems may be more accurately reflected in in vivo findings than in monolayer cultures.
    Tissue Engineering Part A 09/2011; 18(3-4):432-45. · 4.64 Impact Factor

Publication Stats

428 Citations
141.99 Total Impact Points

Institutions

  • 2013–2014
    • Hanyang University
      Sŏul, Seoul, South Korea
    • Kyungpook National University
      • College of Pharmacy
      Sangju, North Gyeongsang, South Korea
  • 2006–2013
    • Seoul National University
      • • Department of Electrical and Computer Engineering
      • • Dental Research Institute
      • • College of Dentistry
      Seoul, Seoul, South Korea
  • 2012
    • Konkuk University
      • Department of Bioscience and Technology
      Sŏul, Seoul, South Korea
  • 2010
    • Korea Institute of Science and Technology
      • Doping Control Center
      Seoul, Seoul, South Korea
    • Korea University
      • Department of Biomedical Engineering
      Sŏul, Seoul, South Korea
  • 2009
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2007
    • Yonsei University
      • College of Nursing
      Sŏul, Seoul, South Korea
  • 2004–2005
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 2003–2005
    • Asan Medical Center
      • Department of Gastroenterology
      Sŏul, Seoul, South Korea