• Title/Summary/Keyword: multi-drug

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Identification of ML106 Phase 1 Metabolites in Human Liver Microsomes Using High-Resolution Quadrupole-Orbitrap Mass Spectrometry

  • Jo, Jun Hyeon;Nam, WoongShik;Kim, Sunjoo;Lee, Doohyun;Min, Kyung Hoon;Lee, Taeho;Lee, Sangkyu
    • Mass Spectrometry Letters
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    • v.7 no.3
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    • pp.69-73
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    • 2016
  • High-resolution quadrupole-Orbitrap mass spectrometry (HRMS), with high-resolution (> 10,000 at full-width at half-maximum) and accurate mass (< 5 ppm deviation) capabilities, plays an important role in the structural elucidation of drug metabolites in the pharmaceutical industry. ML106, a derivative of imidazobenzimidazole, decreased melanin content and tyrosinase activity in a dose-dependent manner. Here, we investigated the phase 1 metabolic pathway of ML106 using HRMS in human liver microsomes (HLMs) and recombinant cDNA-expressed cytochrome P450 (CYP). After the incubation of ML106 with pooled HLMs and recombinant cDNA-expressed CYP in the presence of NADPH, five phase 1 metabolites, including three mono-hydroxylated metabolites (M1-3) and two di-hydroxylated metabolites (M4 and M5), were investigated. The metabolite structures were postulated by the elucidation of protonated mass spectra using HRMS. The CYP isoforms related to the hydroxylation of ML106 were studied after incubation with recombinant cDNA-expressed CYP. Here, we identified the phase 1 metabolic pathway of ML106 induced by CYP in HLMs.

The Diversity of Multi-drug Resistance Profiles in Tetracycline-Resistant Vibrio Species Isolated from Coastal Sediments and Seawater

  • Neela Farzana Ashrafi;Nonaka Lisa;Suzuki Satoru
    • Journal of Microbiology
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    • v.45 no.1
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    • pp.64-68
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    • 2007
  • In this study we examined the multi-drug resistance profiles of the tetracycline (TC) resistant genus Vibrio to determine its susceptibility to two ${\beta}-lactams$, ampicillin (ABPC), and mecillinam (MPC), as well as to macrolide, erythromycin (EM). The results showed various patterns of resistance among strains that were isolated from very close geographical areas during the same year, suggesting diverse patterns of drug resistance in environmental bacteria from this area. In addition, the cross-resistance patterns suggested that the resistance determinants among Vibrio spp. are acquired differently within the sediment and seawater environments.

Anitimicrobial Effects of Zanthoxylum schinifolium Extracts against Multi-drug Resistant Acinetobacter baumannii (산초(Zanthoxylum schinifolium) 추출물의 다제내성 Acinetobacter baumannii 억제 효과)

  • Lee, Keyong-Ho;Rhee, Ki-Hyeong
    • Korean Journal of Pharmacognosy
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    • v.42 no.4
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    • pp.336-340
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    • 2011
  • The aim of this study was to investigate the possible utilization of Zanthoxylum schinifolium as a source of antimicrobial agents. The antimicrobial effects of Zanthoxylum schinifolium extracts were investigated against Acinetobacter baumannii, which is a multi-drug resistant pathogen, and 5 other pathogenic microorganisms. The hexane extract of Zanthoxylum schinifolium was more effective than the ethyl acetate, n-butanol and methanol extracts which were active against Acinetobacter baumannii 25, with minimum inhibitory concentrations(MIC) ranging from 0.8 mg/ml to 1.6 mg/ml. Tetracycline had no effect on Acinetobacter baumanniii. The hexane extract was highly active against Candida albicans IFO 6258, with an MIC of 1.5 mg/ml. In contrast, the ethyl acetate, n-butanol and methanol extracts showed no activity against the 5 pathogenic microorganisms. Furthermore, a combination of hexane extract and ethyl acetate extract was significantly more active against the 5 Acinetobacter baumannii strains than n-butanol and methanol. These results suggest that Zanthoxylum schinifolium extracts have great potential as antimicrobial compounds against multi-drug resistant pathogens, and further studies are warranted.

Simultaneous Quantification of 13 Ginsenosides by LC-MS/MS and its Application in Diverse Ginseng Extracts

  • Jo, Jung Jae;Cho, Pil Joung;Lee, Sangkyu
    • Mass Spectrometry Letters
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    • v.9 no.2
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    • pp.41-45
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    • 2018
  • Ginseng (Panax ginseng Meyer) has been used as traditional herbal drug in Asian countries. Ginsenosides are major components having pharmacological and biological efficacy like anti-inflammatory, anti-diabetic and anti-tumor effects. To control the quality of the components in diverse ginseng products, we developed a new quantitative method using LC-MS/MS for 13 ginsenosides; Rb1, Rb2, Rc, Rd, Re, Rf, 20(S)-Rh1, 20(S)-Rh2, Rg1, 20(S)-Rg3, F1, F2, and compound K. This method was successfully validated for linearity, precision, and accuracy. This quantification method applied in four representative ginseng products; fresh ginseng powder, white ginseng powder, red ginseng extract powder, and red ginseng extract. Here the amounts of the 13 ginsenosides in the various type of ginseng samples could be analyzed simultaneously and expected to be suitable for quality control of ginseng products.

Determination of Flunixin and 5-Hydroxy Flunixin Residues in Livestock and Fishery Products Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

  • Dahae Park;Yong Seok Choi;Ji-Young Kim;Jang-Duck Choi;Gui-Im Moon
    • Food Science of Animal Resources
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    • v.44 no.4
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    • pp.873-884
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    • 2024
  • Flunixin is a veterinary nonsteroidal anti-inflammatory agent whose residues have been investigated in their original form within tissues such as muscle and liver. However, flunixin remains in milk as a metabolite, and 5-hydroxy flunixin has been used as the primary marker for its surveillance. This study aimed to develop a quantitative method for detecting flunixin and 5-hydroxy flunixin in milk and to strengthen the monitoring system by applying to other livestock and fishery products. Two different methods were compared, and the target compounds were extracted from milk using an organic solvent, purified with C18, concentrated, and reconstituted using a methanol-based solvent. Following filtering, the final sample was analyzed using liquid chromatography-tandem mass spectrometry. Method 1 is environmentally friendly due to the low use of reagents and is based on a multi-residue, multi-class analysis method approved by the Ministry of Food and Drug Safety. The accuracy and precision of both methods were 84.6%-115% and 0.7%-9.3%, respectively. Owing to the low matrix effect in milk and its convenience, Method 1 was evaluated for other matrices (beef, chicken, egg, flatfish, and shrimp) and its recovery and coefficient of variation are sufficient according to the Codex criteria (CAC/GL 71-2009). The limits of detection and quantification were 2-8 and 5-27 ㎍/kg for flunixin and 2-10 and 6-33 ㎍/kg for 5-hydroxy flunixin, respectively. This study can be used as a monitoring method for a positive list system that regulates veterinary drug residues for all livestock and fisheries products.

Study on Biological Effect of Multi-Herbal Drug KOCO-P1 on Human Hepatocytes (HepG2) (인간 간조직세포(HepG2 Cells)에 대한 한약조성물 KOCO-P1의 효과 연구)

  • Park, Wan-Su
    • The Korea Journal of Herbology
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    • v.23 no.3
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    • pp.149-154
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    • 2008
  • Objectives : The purpose of this study is to investigate the biological Effect of multi-herbal drug 'KOCO-P1' on human hepatocyte HepG2 cells. Methods : Multi-herbal drug 'KOCO-P1' was composed of Ginseng Radix, Astragali Radix, Polygonati Rhizoma, Liriopis Tuber, and Scrophulariae Radix. Cytotoxicity and cytoprotective activity of KOCO-P1 was verificated by MTT assay. And antioxidative effect of KOCO-P1 against EtOH, Nicotine was inspected by Hydroperoxide assay. Results : KOCO-P1 showed no cytotoxicity on HepG2 cells for 24, 48 hours. KOCO-P1 at 50 ${\mu}g/mL$ reduced the production of H2O2 in HepG2 cells by EtOH. KOCO-P1 at 50 ${\mu}g/mL$ reduced the production of $H_2O_2$ in $HepG_2$ cells by Nicotine. Conclusions : KOCO-P1 at the low concentration could be supposed to have antioxidative effect on human hepatocyte with no cytotoxicity.

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Comparative Analysis of Salmonella enterica subsp. enterica Serovar Thompson Isolates associated with Outbreaks Using PFGE and wgMLST

  • Youngho Koh;Yunyoung Bae;Min-Jung Lee;Yu-Si Lee;Dong-Hyun Kang;Soon Han Kim
    • Journal of Microbiology and Biotechnology
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    • v.32 no.12
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    • pp.1605-1614
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    • 2022
  • The strains associated with foodborne Salmonella enterica Thompson outbreaks in Korea have not been identified. Therefore, we characterized S. Thompson strains isolated from chocolate cakes linked to foodborne outbreaks in Korea. A total of 56 strains were isolated from preserved cake products, products in the supply chain distribution, the manufacturer's apparatus, and egg white liquid products used for cream preparation. Subsequently, serological typing, pathogenic gene-targeted polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE), and whole-genome multi-locus sequence typing (wgMLST) were performed to characterize these isolates. The antigen formula of all isolates was 7:k:1,5, namely Salmonella enterica subsp. enterica Serovar Thompson. All 56 isolates harbored invA, his, hin, and stn, and were negative for sefA and spvC based on gene-targeted PCR analyses. Based on PFGE results, these isolates were classified into one group based on the same SP6X01.011 pattern with 100% similarity. We selected 19 strains based on the region and sample type, which were subjected to wgMLST. Although the examined strains showed 100% similarity, they were classified into seven clusters based on allelic differences. According to our findings, the cause of these outbreaks was chocolate cake manufactured with egg white liquid contaminated with the same Salmonella Thompson. Additionally, comparative analysis of wgMLST on domestic isolates of S. Thompson from the three outbreaks showed genetic similarities of over 99.6%. Based on the results, the PFGE and wgMLST combination can provide highly resolved phylogeny and reliable evidence during Salmonella outbreak investigations.

Drug Release Characteristics and Skin Irritancies of Topical Gels and Multiple Emulsion Creams Containing Kojic Acid (외용겔 및 다중유제크림의 코지산 방출특성과 피부자극성)

  • Yu, Sung-Un;Park, Eun-Woo;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.28 no.2
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    • pp.87-92
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    • 1998
  • Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of the skin irritancy and the instability against the pH, temperature, and light. In order to overcome these problems, various topical gels and multiple emulsion creams which can control the release of active ingredient, KA, were formulated employing cream bases of mineral oil with caprylic capric triglyceride and hydrophilic polymers such as chitosan, carbopol. and pluronics. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solution. Drug release from chitosan-based gels (ChitoGel) obeyed to the first order kinetics with a rapid release especially in the initial period. However, pluronic-based gels (PluGel) and carbopol-based gels (CarboGel) revealed controlled release of drug to some extent, followed by the square root-time kinetics. Moreover, the release of KA was further controlled with the W/O/W multiple emulsion creams (MultiCream), showing the apparent zero order release kinetics by virtue of dynamic ratecontrolling membrane of the oil layer. The flux $(J,\;{\mu}g/cm^2/hr)$ of ChitoGel. CarboGel. PluGel. and MultiCream in the initial period of 6hr were 73.30, 28.67. 24.04 and 7.72, respectively. On the other hand, the skin irritancy score of ChitoGel and MultiCream were observed as 2.5 and 2.3 respectively, in the rabbit skin irritation test. Although there were insignificant differences at p<0.05 between those formulations, it was possible to conclude that the W/O/W multiple emulsion creams containing KA might be a good candidate for an antimelanogenic drug delivery system due to the controlled release of acidic drug molecules.

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DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes

  • Shon, Jong Cheol;Joo, Jeongmin;Lee, Taeho;Kim, Nam Doo;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • v.9 no.1
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    • pp.24-29
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    • 2018
  • DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.