• Title/Summary/Keyword: drug residues

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Application of biodegradable metal based drug delivery carrier on Foot and Mouth Disease vaccination in pigs (돼지에서 생체 분해 금속성 전달체를 활용한 구제역 백신의 적용 연구)

  • Cho, Ara;Oh, Sang-Ik;Choe, Changyong;Jung, Young-Hun;Do, Yoon Jung;Kim, Suhee;Choo, Hyun Wook;Gu, Jong Su;Chung, Woo-Jin;Cho, Sung Youn;Yoo, Jae Gyu
    • Korean Journal of Veterinary Service
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    • v.43 no.3
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    • pp.129-137
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    • 2020
  • In this study, we applied biodegradable drug delivery carries (BDDC) for food-and-mouth (FMD) vaccination. After FMD vaccination using BDDC, we estimated the percentage inhibition (PI) of antibody, decomposed patterns, and histopathologic features of BDDC. PI of antibody was higher than 50 at two weeks after injection and sustained positive PI until 10 weeks after injection. BBDC injection group showed significantly an increased pattern of blood monocyte at two and three weeks after injection. According to the Micro CT, micro-cracks were observed at two weeks after injection and the morphology of BDDC was lost at four weeks after injection. For histopathological examination, acute inflammation with neutrophil infiltration and micro-metallic residues were observed around BDDC until four weeks after injection and inflammatory responses gradually decreased at 10 weeks. Based on our experiment, BDDC is considered as an alternative way to vaccine injection for veterinary applications. Our study can be used as basic data for the drug delivery system using biodegradable metals in the future.

Discovery of Cyclin-dependent Kinase Inhibitor, CR229, Using Structure-based Drug Screening

  • Kim, Min-Kyoung;Min, Jae-Ki;Choi, Bu-Young;Lim, Hae-Young;Cho, Youl-Hee;Lee, Chul-Hoon
    • Journal of Microbiology and Biotechnology
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    • v.17 no.10
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    • pp.1712-1716
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    • 2007
  • To generate new scaffold candidates as highly selective and potent cyelin-dependent kinase (CDK) inhibitors, structure-based drug screening was performed utilizing 3D pharmacophore conformations of known potent inhibitors. As a result, CR229 (6-bromo-2,3,4,9-tetrahydro-carbolin-1-one) was generated as the hit-compound. A computational docking study using the X-ray crystallographic structure of CDK2 in complex with CR229 was evaluated. This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Furthermore, biochemical studies on inhibitory effects of CR229 on various kinases in the human cervical cancer HeLa cells demonstrated that CR229 was a potent inhibitor of CDK2 ($IC_{50}:\;3\;{\mu}M$), CDKI ($IC_{50}:\;4.9\;{\mu}M$), and CDK4 ($IC_{50}:\;3\;{\mu}M$), yet had much less inhibitory effect ($IC_{50}:>20\;{\mu}M$) on other kinases, such as casein kinase 2-${\alpha}1$ (CK2-${\alpha}1$), protein kinase A (PKA), and protein kinase C (PKC). Accordingly, these data demonstrate that CR229 is a potent CDK inhibitor with anticancer efficacy.

Virtual Screening for Potential Inhibitors of NS3 Protein of Zika Virus

  • Sahoo, Maheswata;Jena, Lingaraja;Daf, Sangeeta;Kumar, Satish
    • Genomics & Informatics
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    • v.14 no.3
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    • pp.104-111
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    • 2016
  • Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of -5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of -7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.

Development of Analytic Methods for Veterinary Drug Residue in Animal Products by Liquid Chromatography-Mass Spectrometry (축산물 중 잔류 성장보조제 분석을 위한 액체크로마토그라피-질량분석법 개발 및 적용)

  • Lee, Soo Hyun
    • Journal of Convergence for Information Technology
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    • v.11 no.2
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    • pp.107-116
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    • 2021
  • In this study, an analytical method was developed for estradiol-17��, testosterone, and progesterone, which are growth promoters as veterinary drug residues in animal food. The analytes were separated using liquid chromatography, and was injected into a mass spectrometer through the electrospray ionization(ESI) process and detected in multiple reaction monitoring(MRM) mode. As the method was validated by CODEX CAC/GL 71-2009 guideline, it met the acceptable. The analysis of beef, pork, and chicken distributed in Korea was conducted with an established method to confirm the applicability of the actual sample. It was confirmed that the developed method can be quickly and reliably in the analysis for the growth promoters identified in domestic distributed livestock products. Through subsequent research, a highly utilized analysis method will be completed if the number of growth promoters is expanded based on the method and the simultaneous analytical method is established by including all of it.

Establishment of withdrawal time and analysis of tiamulin residue in tissues of orally dosed broiler chickens (육계의 조직 중 티아물린의 잔류 분석 및 휴약기간 설정 연구)

  • Woo H. Kim;Jun Young Kim;Kwang Il Park;Yeung Bae Jin;Suk Kim;Hu-Jang Lee
    • Korean Journal of Veterinary Research
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    • v.63 no.3
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    • pp.23.1-23.9
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    • 2023
  • This study was conducted to investigate tiamulin (TML) residues in the edible tissues of orally dosed broiler chickens and to re-establish the withdrawal time (WT). Thirty-six healthy Ross broiler chickens were administered 0.5 (TML-1) and 2.5 kg (TML-2) per ton feed, respectively, of the drug containing TML 78 g/kg for 10 days. Twenty-four tissue samples were collected from 6 chickens in each of the TML-1 and TML-2 groups on 0, 1, 3, and 5 days after drug administration, respectively. The residual concentrations of TML were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation coefficient of the calibration curves was 0.9978 to 0.9998, and the limits of detection and the limits of quantification (LOQ) were in the range of 0.03 to 0.06, and 0.1 to 0.2 ㎍/kg, respectively. Recoveries ranged between 89.0% to 116.7%, and the coefficients of variation were less than 13.9%. After the drug administration, TML in the TML-1 and TML-2 groups was detected above the LOQ in 1 and 6 samples of liver, respectively, at day 0, and in 1 liver sample from both groups on day one. At 3 days after administration, TML was detected below the LOQ in all samples of TML-1 and TML-2. The calculated WT of TML in both TML-1 and TML-2 using the WT calculation program WT 1.4 was 0 days. In conclusion, the developed analytical method is suitable for detection, and the calculated WT of TML in poultry edible tissues is shorter than the current recommended WT of 7 days for TML in broiler chickens.

Recent Progress in Mussel-inspired Catechol-conjugated Chitosan Hemostats (홍합 모사 카테콜기가 도입된 키토산 지혈제 연구 동향)

  • Seongyeon Jo;Soomi Kim;Chanwoo Park;Seungwon Hong;Hong Kee Kim;Ji Hyun Ryu
    • Journal of Adhesion and Interface
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    • v.24 no.4
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    • pp.113-119
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    • 2023
  • Since it was reported that the unusual amino acid DOPA in synergy with lysine and histidine residues found in mussel adhesive proteins plays a pivotal role in mussel adhesion in underwater environments, there has been a burgeoning development of various catecholamines-based adhesives for biomedical applications. Among these, catechol-conjugated chitosan, containing catecholamine, featuring multiple catechol groups within its aminerich chitosan backbone, has found versatile utility in fields, such as tissue adhesion, wound dressing, tissue healing, hemostats, drug delivery systems, and tissue engineering scaffolds. Significantly, chitosan-catechol is a mussel-inspired material approved by both US Food and Drug Administration (FDA) and KR Ministry of Food and Drug Safety (MFDS) for its effectiveness in hemostasis. This review focuses on 1) general aspects of catechol-conjugated chitosan, highlighting catechol group integration into chitosan backbones, 2) examination of proposed mechanisms of hemostasis, and 3) exploration of diverse physical forms, including solution, hydrogels, patches, and thin films with practical applications inapplicable to hemostasis.

Monitoring of Ergosterol Biosynthesis Inhibitor (EBI) Pesticide Residues in Commercial Agricultural Products and Risk Assessment (국내 유통 농산물 중 EBI계 농약 모니터링과 위해도 평가)

  • Lee, Hee-Jung;Choe, Won-Jo;Lee, Ju-Young;Cho, Dae-Hyun;Kang, Chan-Soon;Kim, Woo-Seong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.12
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    • pp.1779-1784
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    • 2009
  • Establishment of simultaneous analysis method and monitoring for individually analyzing residual eight ergosterol biosynthesis inhibitors, EBI (difenoconazole, diniconazole, fenarimol, fenbuconazole, hexaconazole, myclobutanil, nuarimol and paclobutrazol) pesticides in commercial agricultural products, were conducted. The simultaneous analysis method for the pesticides was established using a GC/MS/MS for EBI pesticides. Residual amount of those pesticides were investigated in 989 commercial agricultural products (fifteen kinds of cereal grains, vegetables, beans, nuts, fruits and mushrooms) from seven metropolitan cities and eight provinces. In EBI pesticides analysis, linearity of GC/MS/MS analysis was 0.9974-0.9992, and that of recoveries were 86-135% with relative standard deviations (RSD) <20%. The limit of quantification (LOQ) of the method ranged from 0.5 to 5.0 mg/kg for eight EBI pesticides. According to the monitoring of the EBI pesticides in commercial agricultural products, difenoconazole, fenarimol, hexaconazole showed various residual levels (total frequency of 8/989 detection, 0.8%). Paclobutrazole showed in excess levels of the MRLs (maximum residue limits) for pesticides in one chard sample by the Korea Food Code. As a result of exposure assessment on the detected 8 individual pesticides, all pesticides (difenoconazole, fenarimol, hexaconazole, paclobutrazole) were evaluated as safe level in comparison to toxicologically acceptable daily intake.

Market survey on total bromide residues in foods (국내유통 식품중 total bromide의 잔류량)

  • Park, Kun-Sang;Hong, Moo-Ki;Choi, Dong-Mi;Oh, Chang-Hwan;Hwang, In-Gyun;Park, Jong-Sei
    • The Korean Journal of Pesticide Science
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    • v.2 no.1
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    • pp.65-69
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    • 1998
  • To determine the amount of total bromide as 2-bromoethanol, the domestic agricultural products such as rice, barley, carrot, cucumber, apple, tomato, squash, green pepper, melon, strawberry, grape, peach, potato and celery were analyzed by GC/MSD as well as GC/ECD. The bromide was detected in most of the domestic samples and the highest bromide residue determined was 13.2 ppm in barley. The imported agricultural products including melon, kiwi, lemon, pineapple, banana, orange and grape were also analyzed for the bromide. The bromide was also detected in most of the imported ones and the highest bromide residue determined was 12.3 ppm in pineapple. In addition, the bromide residue in instant noodle spices was monitored for 4 years, recently. As results, in 1994, the bromide content was in the range of non-detection to 2.4 ppm (average 1.1 ppm) from 22 out of 24 samples; in 1995, the bromide content was 1.0 and 2.2 ppm from 2 out of 37 samples; in 1996, the bromide content was in the range of 0.7 to 37 ppm (average 12.4 ppm) from all 11 samples; and in 1997, the bromide content was in the range of 0.2 to 4.6 ppm (average 1.2 ppm) from all 59 samples. However, none of sample analyzed for the bromide was exceeded Maximum Residue Limit(s) of Korea and Codex in these survey.

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Development of Analytical Method and Monitoring for Bifenazate in Commercial Agricultural Products (농산물 중 Bifenazate의 분석법 개선 및 모니터링)

  • Park, Eun-Heui;Go, Myoung-Jin;Cho, Myong-Shik;Kim, Young-Sun;Lee, Jin-Ha;Choi, Dong-Mi
    • The Korean Journal of Pesticide Science
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    • v.14 no.1
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    • pp.21-29
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    • 2010
  • The analytical method for bifenazate was developed using a HPLC (UVD). Also, analytical condition of LC/MS was set up for bifenazate. We validated the method for the precision and the reproducibility. The correlation coefficient of bifenazate ranged from 0.05 to 2.5 mg/kg was 1.0. Limit of quantitation (LOQ) was 0.01 mg/kg. To measure recoveries from agricultural products such as foxtail millet (cereal grains), kidney bean (beans), orange (fruits), perilla leaves (vegetables) and oak mushroom (mushrooms), bifenazate was spiked. Mean recoveries of bifenazate for each sample were 82.7~104.1% at the level of 0.1 mg/kg and 73.1~104.3% at the level of 0.5 mg/kg. The relative standard deviations (n=3) were 0.2~9.7%. Pesticide residues for bifenazate were investigated in 16 commodities (rice, foxtail millet, buckwheat, kidney bean, peanut, sesame, orange, grapefruit, kiwifruit, spinach, perilla leaves, leek, garlic stem, garlic, ginger and oak mushroom) collected from 22 provinces in 2009. Bifenazate was analyzed using analytical method by HPLC from 304 samples, and residue was not detected.

Determination of lercanidipine in human plasma by LC-MS/MS (LC-MS/MS를 이용한 혈장 중 레르카니디핀의 분석)

  • Jang, Moon-Sun;La, Sookie;Chang, Kyu Young;Kang, Seung Woo;Han, Sang Beom;Lee, Kyung Ryul;Lee, Hee Joo
    • Analytical Science and Technology
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    • v.21 no.1
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    • pp.34-40
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    • 2008
  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of lercanidipine in human plasma. After addition of internal standard (amlodipine), plasma was precipitated with acetonitrile and the supernatant was evaporated. The residues were dissolved in 50 % acetonitrile and analyzed by LC-MS/MS. Using MS/MS with multiple reaction monitoring(MRM) mode, lercanindipine were selectively detected without severe interference from human plasma. The standard calibration curve for lercanidipine was linear (r = 0.9994) over the concentration range 0.05-20.0 ng/mL in human plasma. The intra- and inter-day precision over the concentration range of lercanidipine was lower than 11.7 % (correlation of variance, CV), and accuracy was between 94.4-114.8 %. This method has been successfully applied to the pharmacokinetic study of lercanidipine in human plasma.