• Title/Summary/Keyword: drug residues

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Solution Structure of Human Orexin-A: Regulator of Appetite and Wakefulness

  • Kim, Hai-Young;Hong, Eun-Mi;Kim, Jae-Il;Lee, Weon-Tae
    • BMB Reports
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    • v.37 no.5
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    • pp.565-573
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    • 2004
  • Orexin-A and orexin-B (hypocretin-1 and hypocretin-2, respectively) are important hypothalamic neuro-peptides, which are encoded by a single mRNA transcript and stimulate food intake as well as regulate wakefulness. Here we determined the solution structure of orexin-A by NMR spectroscopy and by simulated-annealing calculation. The structural features of orexin-A involve two $\alpha$-helices, with the hydrophobic residues disposed to on one side of helix, and hydrophilic residues to the other. A hydrophilic turn induced by two disulfide bonds provides the key difference between orexin-A and -B. With previous mutagenic studies, the derived structure of orexin-A provides us with a structure-functional view for novel drug design.

Protein-Protein Interaction between Poly(A) Polymerase and Cyclophilin A in Chemotactic Cells

  • Choi, Hyun-Sook;Kim, Hana;Lee, Changgook;Kim, Youngmi;Lee, Younghoon
    • Bulletin of the Korean Chemical Society
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    • v.35 no.1
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    • pp.83-86
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    • 2014
  • Poly(A) polymerase (PAP) play an essential role for maturation of mRNA by adding the adenylate residues at the 3' end. PAP functions are regulated through protein-protein interaction at its C-terminal region. In this study, cyclophilin A (CypA), a member of the peptidyl-prolyl cis-trans isomerase family, was identified as a partner protein interacting with the C-terminal region PAP. The interaction between PAP and CypA was inhibited by the immunosuppressive drug cyclosporine A. Deletion analysis revealed that the N-terminal 56 residues of CypA are sufficient for the interaction with PAP. Interestingly, we observed that PAP and CypA colocalize in the nucleus during SDF-1-induced chemotaxis, implying that CypA could be involved in the regulation of polyadenylation by PAP in the chemotactic cells.

Development and validation of an analytical method for nematicide imicyafos determination in agricultural products by HPLC-UVD (HPLC-UVD를 이용한 살선충제 imicyafos의 시험법 개발 및 검증)

  • Do, Jung-Ah;Park, Hyejin;Kwon, Ji-Eun;Choi, Won-Jo;Lee, Hyun-Sook;Chang, Moon-Ik;Hong, Jin-Hwan;Oh, Jae-Ho
    • Analytical Science and Technology
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    • v.27 no.5
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    • pp.234-242
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    • 2014
  • Imicyafos which is a nematicide for controlling root-knot nematodes has been registered in the Republic of Korea in 2012, and the maximum residue limits of imicyafos are set to watermelon and korean melon as each 0.05 mg/kg. Extremely reliable and sensitive analytical method is required for ensuring food safety on imicyafos residues in agricultural commodities. Imicyafos residues in samples were extracted with acetone, partitioned with hexane and dichloromethane, and then purified with florisil. The purified samples were analyzed by HPLC-UVD and confirmed with LC-MS. Linear range was between 0.1~5 mg/kg with the correlation coefficient ($r^2$) 0.99997. Average recoveries of imicyafos ranged from 77.0 to 115.4% at the spiked levels of 0.02 and 0.05 mg/kg with the relative standard deviations of 2.2~9.6%. Limit of detection and quantification were 0.005 and 0.02 mg/kg, respectively. An inter-laboratory study was conducted to validate the determination method in depth, and the results were satisfactory. All of the validation results revealed that the developed analytical method in this study is relevant for imicyafos determination in agricultural commodities and will be used as an official analytical method.

Biochemical changes and drug residues in ascidian Halocynthia roretzi after formalin-hydrogen peroxide treatment regimen designed against soft tunic syndrome

  • Lee, Ji-Hoon;Kim, Ju-Wan;Shin, Yun-Kyung;Park, Kyung-Il;Park, Kwan Ha
    • Fisheries and Aquatic Sciences
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    • v.20 no.7
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    • pp.12.1-12.7
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    • 2017
  • Soft tunic syndrome (STS) is a protozoal disease caused by Azumiobodo hoyamushi in the edible ascidian Halocynthia roretzi. Previous studies have proven that combined formalin-hydrogen peroxide ($H_2O_2$) bath is effective in reducing STS progress and mortality. To secure target animal safety for field applications, toxicity of the treatment needs to be evaluated. Healthy ascidians were bathed for 1 week, 1 h a day at various bathing concentrations. Bathing with 5- and 10-fold optimum concentration caused 100% mortality of ascidians, whereas mortality by 0.5- to 2.0-fold solutions was not different from that of control. Of the oxidative damage parameters, MDA levels did not change after 0.5- and 1.0-fold bathing. However, free radical scavenging ability and reducing power were significantly decreased even with the lower-than-optimal 0.5-fold concentration. Glycogen content tended to increase with 1-fold bathing without statistical significance. All changes induced by the 2-fold bathing were completely or partially restored to control levels 48 h post-bathing. Free amino acid analysis revealed a concentration-dependent decline in aspartic acid and cysteine levels. In contrast, alanine and valine levels increased after the 2-fold bath treatment. These data indicate that the currently established effective disinfectant regimen against the parasitic pathogen is generally safe, and the biochemical changes observed are transient, lasting approximately 48 h at most. Low levels of formalin and $H_2O_2$ were detectable 1 h post-bathing; however, the compounds were completely undetectable after 48 h of bathing. Formalin-$H_2O_2$ bathing is effective against STS; however, reasonable care is required in the treatment to avoid unwanted toxicity. Drug residues do not present a concern for consumer safety.

Monitoring of Veterinary Drug Residues in Cultured Fishery Products in Chungcheongnam-do Province (충남지역에서 생산되는 양식수산물의 잔류 동물용의약품 모니터링)

  • Lee, Kang-Bum;Kim, Nam-Woo;Kim, Dong-Uk;Sin, Myeong-Hee;Lee, Mi-Young
    • Journal of Food Hygiene and Safety
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    • v.35 no.5
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    • pp.447-451
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    • 2020
  • For this study, we conducted a simultaneous multiresidue analysis of veterinary drugs in cultured fishery products in Chungnam Province in 2018. A total of 115 fishery product samples were obtained from fish farms and fishery production sites located in the province. In all, 29 residual veterinary drugs in the samples were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. As a result, veterinary drug residues were only detected in a small number of the 106 samples (92.2%), and the detection rate was 7.8% (9 of 115 samples). The amounts were also below maximum residual limit (MRL) for fishery products, although one sample exceeded the MRL allowed by the Ministry of Food and Drug Safety and was detected in loach. The nine residual veterinary drugs were detected in 8 samples: loach, eel, catfish, freshwater bream, flatfish, rockfish and shrimp. The detected veterinary drugs were oxolinic acid, enrofloxacin, ciprofloxacin, sulfadiazine, flumequine and oxytetracycline. The most frequently detected antibiotic was oxolinic acid, and enrofloxacin exceeded the MRL in loach sample. Residues of most veterinary drugs were either not detected or were below the MRL, and while the status of fishery products is seen as safe overall, current surveillance efforts over veterinary drugs should be continued.

Molecular Characterization of Legionellosis Drug Target Candidate Enzyme Phosphoglucosamine Mutase from Legionella pneumophila (strain Paris): An In Silico Approach

  • Hasan, Md. Anayet;Mazumder, Md. Habibul Hasan;Khan, Md. Arif;Hossain, Mohammad Uzzal;Chowdhury, A.S.M. Homaun Kabir
    • Genomics & Informatics
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    • v.12 no.4
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    • pp.268-275
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    • 2014
  • The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.

Farnesylcysteine Methyltransferase Activity and Ras Protein Expression in Human Stomach Tumor Tissue

  • Han, Eui-Sik;Oh, Hye-Young;Ha, Kwang-Won;Han, Beom-Seok;Hong, Seok-Min;Han, Jung-Whwan;Hong, Sung-Youl;Noh, Sung-Hun;Lee, Hyang-Woo
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.378-384
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    • 1998
  • The processing pathway of G-proteins and Ras family proteins includes the isoprenylation of the cysteine residue, followed by proteolysis of three terminal residues and .alpha.-carboxyl methyl esterification of the cysteine residue. Farnesylcysteine methyltransferase (FCMT) activity is responsible for the methylation reaction which play a role in the membrane attachment of a variety of cellular proteins. Four kinds of Ras protein (c-Ha-ras, c-N-Ras, c-Ki-Ras, pan-Ras) expression were detected in adenocarcinoma of human tissue by immunohistochemical method, and hematoxylin and eosin staining. The level of Ras protein in human stomach tumor tissues was much higher than in normal and peritumoral regions of the same biopsy samples. The FCMT activities of each cellular fractions were high in mitochondrial fraction followed by microsomal fraction, whole homogenate and cytosolic fraction. The inhibitory effect on FCMT activity on stomach tumor tissue was determined after treatment with 0.25 $\mu\textrm{M}$ of S-adenosyl-$_L$-homocysteine. S-adenosyl-$_L$-homocysteine inhibited FCMT activity from 11.2% to 30.5%. These results suggested that FCMT might be involved in Ras proteins activity.

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Determination of residual flumethrin in honey products by HPLC (HPLC를 이용한 벌꿀 중 플루메쓰린 분석)

  • Won, So-Young;Jeong, Young-Ji;Lee, Hwee-Jae;Chang, Hye-Sook;Bahn, Kyeong-Nyeo;Kang, Ho-Il;Kim, So-Hee
    • Analytical Science and Technology
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    • v.22 no.6
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    • pp.458-463
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    • 2009
  • A new quantitative analytical method has been established for the rapid determination of flumethrin in honey products using high performance liquid chromatography (HPLC). Sample was dissolved and extracted in the mixture of water and acetonitrile (1:2). The extracts were purified with silica cartridge eluted by the mixture of hexane and dichloromethane (55:45) and analyzed at 266 nm using HPLC. The percentage recovery of flumethrin spiked in sample was found to be 90.2-97.8% and the limit of detection is 0.003 mg/kg. We validated the method for the linearity, the precision and the reproducibility. We investigated the residues of flumethrin in honey products retailed in market using the established method. Flumethrin was not detected at all among 130 samples of honey.

Monitoring of Pesticide Residues and Risk Assessment of Agricultural Products Consumed in South Korea (국내유통농산물 중 잔류농약 모니터링 및 안전성 평가)

  • Kim, Sung-Hun;Choe, Won-Jo;Baik, Yong-Kyoo;Kim, Woo-Seong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.11
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    • pp.1515-1522
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    • 2008
  • Monitoring the pesticide residues in agricultural products is essential to protect consumers, obtain data for risk assessment, and ensure fair trade practices. We developed a multi-residue method for the analysis of 37 pesticides with different physico-chemical properties in agricultural products and analyzed the amount of pesticide residues on about 1,000 samples circulated in South Korea. The samples consisted of 26 different types of agricultural products selected at markets in 14 major cities; cereals (2 species), nuts (1 species) potatoes (1 species), beans (2 species), fruits (3 species), vegetables (16 species), and mushrooms (1 species). In this study, residual pesticides were detected in 23 samples (2.2%) and one sample was detected to be over maximum residue limits (MRLs, 0.1%) for pesticides in foods by the Korea food code. In leafy vegetables such as pepper leaves, radish leaves, cham-na-mul, shin-sun-cho, crown daisy, chwi-na-mul and citrus fruits such as kumquat, 8 kinds of pesticides were detected. Specially, diazinon were detected over MRLs and also, endosulfan, ethoprophos and phenthoate were detected frequently. Based on these results, we investigated the risk assesment from amount of residual pesticide, total %ADI was 1.262%, but the value has not effected on human health.

Cleaning Validation Studies for Multi-Purpose Facility : Vial Filling Machine (다품목 공용 제약설비인 바이알 충전기에 대한 세척공정 밸리데이션)

  • Choi, Han-Gon;Yang, Ho-Joon;Kim, Young-Ran;Sung, Jun-Ho;Hwang, Ma-Ro;Kim, Jong-Oh;Yong, Chul-Soon
    • Journal of Pharmaceutical Investigation
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    • v.39 no.4
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    • pp.263-267
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    • 2009
  • The purpose of this study is to evaluate the efficacy of stipulated cleaning process, and the prohibition of cross-contamination and microbiological contamination, which inadequate cleaning in multi-production could occur, through cleaning validation of multi-purpose facility used to produce five biopharmaceutical products as sterile injection. After production of five biopharmaceutical products such as hGH, rhGCSF, rhEPO, rhFSH and rhIFN using vial filling machine, the cleaning validation such as residual analysis of active ingredients or human serum albumin, measurement of total organic carbon (TOC), residual analysis of detergent and microbiological contamination were carried out. In the case of rhGH and rhGCSF clean validations, drug residues were not detected. Furthermore, in the case of rhEPO, rhFSH and rhIFN clean validations, human serum albumin residues were not detected. At TOC (total organic carbon) analysis, all clean validations gave the TOC of about average 137.93%, not more than 150% of acceptance criteria. At sodium analysis for the checking of residues of cleaning agent, sodium residues were not detected. In sterility test, they showed no microbiological contamination of bacteria and fungi. Thus, this cleaning validation was determined as successful in protection of cross-contamination and induction of safety in multi-purpose facility.