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https://www.readbyqxmd.com/read/28102586/creatinine-in-urine-a-method-comparison
#1
Marc Luginbühl, Wolfgang Weinmann
Drug screening in urine is widely applied in forensic toxicology. Contrary to blood analysis, excessive or reduced fluid intake can substantially alter the concentration of substances in urine. As a standard to detect urinary dilution, creatinine concentrations are analyzed. A sample with a concentration below 20 mg/dL is generally defined as too diluted to provide a valid result in abstinence control samples. This work investigates the potential of three different methods for the determination of creatinine concentrations in urine samples: A ZIC-HILIC based LC-MS/MS method, a spectrophotometric method on an AU 480 chemistry system, and a portable, immunoassay based point-of-care testing device was compared by measuring 200 urine samples...
January 19, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28102538/comparing-early-liver-graft-function-from-heart-beating-and-living-donors-a-pilot-study-aiming-to-identify-new-biomarkers-of-liver-injury
#2
Qi Joy Yang, Michael Kluger, Krzysztof Goryński, Janusz Pawliszyn, Barbara Bojko, Ai-Ming Yu, Keumhan Noh, Markus Selzner, Angela Jerath, Stuart McCluskey, K Sandy Pang, Marcin Wąsowicz
: Liver and kidney functions among recipients of liver transplantation (LT) surgery with heart beating (HBD, n = 13) or living donors (LD, n = 9) with different cold ischemic times were examined during the neohepatic phase for clearing rocuronium bromide (ROC, cleared by liver and kidney) and tranexamic acid (TXA, cleared by kidney). Solid phase micro-extraction and LC-MS/MS was applied to determine the plasma concentrations of ROC and TXA, and creatinine was determined by standard laboratory methods...
January 19, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28102315/methyl-cytosine-driven-structural-changes-enhance-adduction-kinetics-of-an-exon-7-fragment-of-the-p53-gene
#3
Spundana Malla, Karteek Kadimisetty, You-Jun Fu, Dharamainder Choudhary, John B Schenkman, James F Rusling
Methylation of cytosine (C) at C-phosphate-guanine (CpG) sites enhances reactivity of DNA towards electrophiles. Mutations at CpG sites on the p53 tumor suppressor gene that can result from these adductions are in turn correlated with specific cancers. Here we describe the first restriction-enzyme-assisted LC-MS/MS sequencing study of the influence of methyl cytosines (MeC) on kinetics of p53 gene adduction by model metabolite benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), using methodology applicable to correlate gene damage sites for drug and pollutant metabolites with mutation sites...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102076/kinobead-and-single-shot-lc-ms-profiling-identifies-selective-pkd-inhibitors
#4
Martin Golkowski, Rama Subba Rao Vidadala, Chloe K Lombard, Hyong Won Suh, Dustin J Maly, Shao-En Ong
ATP-competitive protein kinase inhibitors are important research tools and therapeutic agents. Because there are >500 human kinases that contain highly conserved active sites, the development of selective inhibitors is extremely challenging. Methods to rapidly and efficiently profile kinase inhibitor targets in cell lysates are urgently needed to discover selective compounds and to elucidate the mechanisms of action for polypharmacological inhibitors. Here, we describe a protocol for microgram-scale chemoproteomic profiling of ATP-competitive kinase inhibitors using kinobeads...
January 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28101991/clinically-distinct-phenotypes-of-canavan-disease-correlate-with-residual-aspartoacylase-enzyme-activity
#5
Marisa I Mendes, Desirée Ec Smith, Ana Pop, Pascal Lennertz, Matilde R Fernandez Ojeda, Warsha A Kanhai, Silvy J M van Dooren, Yair Anikster, Ivo Barić, Carolien Boelen, Jaime Campistol, Lonneke de Boer, Ariana Kariminejad, Hulya Kayserili, Agathe Roubertie, Krijn T Verbruggen, Christine Vianey-Saban, Monique Williams, Gajja S Salomons
We describe 14 patients with 12 novel missense mutations in ASPA, the gene causing Canavan disease (CD). We developed a method to study the effect of these 12 variants on the function of aspartoacylase - the hydrolysis of N-acetyl-L-aspartic acid (NAA) to aspartate and acetate. The wild-type ASPA open reading frame (ORF) and the ORFs containing each of the variants were transfected into HEK293 cells. Enzyme activity was determined by incubating cell lysates with NAA and measuring the released aspartic acid by LC-MS/MS...
January 19, 2017: Human Mutation
https://www.readbyqxmd.com/read/28101682/synthesis-spectral-and-extended-spectrum-beta-lactamase-studies-of-transition-metal-tetraaza-macrocyclic-complexes
#6
Dinesh Kumar, Nutan Sharma, Manjula Nair
Urinary tract infections commonly occur in humans due to microbial pathogens invading the urinary tract, which can bring about a range of clinical symptoms and potentially fatal sequelae. The present study is aimed at addressing the development of a new antimicrobial agent against extended spectrum beta lactamase (ESBL) producing E. coli bacteria. We have synthesised some biologically potent (NNNN) donor macrocycles (L 1  = dibenzo[f,n]dipyrido[3,4-b:4',3'-j][1,4,9,12]tetraazacyclohexadecine-6,11,18,23(5H,12H, 7H, 24H)-tetraone, and L 2  = 6,12,19,25-tetraoxo-4,6,11,12,16,18,23,24-octahydrotetrabenzo [b,g,k,p][1,5,10,14]tetra azacyclooctadecine-2,13-dicarboxylic acid) and their Ti and Zr metal complexes in alcoholic media using microwave protocol...
January 18, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28099886/itraq-based-quantitative-proteome-revealed-metabolic-changes-of-flammulina-velutipes-mycelia-in-response-to-cold-stress
#7
Jing-Yu Liu, Jun-Long Men, Ming-Chang Chang, Cui-Ping Feng, Ling-Gang Yuan
: Temperature is one of the pivotal factors influencing mycelium growth and fruit-body formation of Flammulina velutipes. To gain insights into hyphae growth and fruit-body formation events and facilitate the identification of potential stage-specific biomarker candidates, we investigated the proteome response of F. velutipes mycelia to cold stresses using iTRAQ-coupled two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) technique. Among 1198 proteins identified with high confidence, a total of 63 displayed altered expression level after cold stress treatments...
January 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28099809/a-gemcitabine-based-peptide-conjugate-with-improved-metabolic-properties-and-dual-mode-of-efficacy
#8
Theodoros Karampelas, Eleni Skavatsou, Orestis Argyros, Demosthenes Fokas, Constantin Tamvakopoulos
Gemcitabine is a clinically established anticancer agent potent in various solid tumors but limited by its rapid metabolic inactivation and off-target toxicity. We have previously generated a metabolically superior to gemcitabine molecule (GSG) by conjugating gemcitabine to a gonadotropin releasing hormone receptor (GnRH-R) ligand peptide, and showed that GSG was efficacious in a castration resistant prostate cancer (CRPC) animal model. The current manuscript provides an in-depth metabolic and mechanistic study of GSG, coupled with toxicity assays that strengthen the potential role of GSG in the clinic...
January 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28099407/effects-of-functional-cyp2c8-cyp2c9-cyp3a5-and-abcb1-genetic-variants-on-the-pharmacokinetics-of-insulin-sensitizer-pioglitazone-in-chinese-han-individuals
#9
Sheng-Ju Yin, Hui-Min Qi, Xin Wang, Pu Zhang, Yuan Lu, Min-Ji Wei, Pu Li, Guang-Zhao Qi, Ya-Qing Lou, Chuang Lu, Guo-Liang Zhang
BACKGROUND AND OBJECTIVES: Pioglitazone is a thiazolidinedione antihyperglycemic drug with insulin-sensitizing properties. We investigated whether the variant genotypes of cytochrome P450 2C8 (CYP2C8), CYP2C9, CYP3A5 and transporter ABCB1 influence the pharmacokinetic phenotype of the substrate pioglitazone in Chinese individuals. PARTICIPANTS AND METHODS: Single-nucleotide polymorphisms were determined by the PCR-restriction fragment length polymorphism method in 244 (CYP2C8 and CYP2C9) healthy Chinese Han individuals...
January 17, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28099191/long-acting-combination-anti-hiv-drug-suspension-enhances-and-sustains-higher-drug-levels-in-lymph-node-cells-than-in-blood-cells-and-plasma
#10
John C Kraft, Lisa A McConnachie, Josefin Koehn, Loren Kinman, Carol Collins, Danny D Shen, Ann C Collier, Rodney J Y Ho
OBJECTIVE: To determine if a combination of anti-HIV drugs-tenofovir (TFV), lopinavir (LPV), and ritonavir (RTV)-in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma. DESIGN: Four macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analyzed using a validated combination LC-MS/MS assay...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28097886/reagent-free-lc-ms-ms-based-pharmacokinetic-quantification-of-polyhistidine-tagged-therapeutic-proteins
#11
Jianxia Shi, Jing Man Wong, Ji Ma, Tiffany Dickerson, Colin Hall, Dan A Rock, Timothy J Carlson
AIM: Immobilized metal ion affinity chromatography is widely employed for purifying polyhistidine-tagged recombinant proteins from cell lysates. The technique can be applied for quantification of therapeutic proteins in biological matrices by LC-MS/MS. RESULTS: A protein reagent-free workflow was developed for quantifying polyhistidine-tagged proteins by LC-MS/MS. The workflow includes target protein enrichment by immobilized metal ion affinity chromatography, on-bead trypsin digestion and quantification of signature peptides by LC-MS/MS...
January 18, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28097740/in%C3%A2-vivo-dearomatization-of-the-potent-antituberculosis-agent-btz043-via-meisenheimer-complex-formation
#12
Florian Kloss, Viktor Krchnak, Anna Krchnakova, Sebastian Schieferdecker, Julia Dreisbach, Volker Krone, Ute Möllmann, Michael Hoelscher, Marvin J Miller
Nitrobenzothiazinones are among the most potent antituberculosis agents. Herein, we disclose an unprecedented in vivo reduction process that affords Meisenheimer complexes of the clinical candidates BTZ043 and PBTZ169. The reduction is reversible, occurs in all mammalian species investigated, has a profound influence on the in vivo ADME characteristics, and has considerable implications for the design and implementation of clinical studies. The reduction was confirmed by chemical studies that enabled the complete characterization of the Meisenheimer complex and its subsequent chemistry...
January 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28095889/evolution-of-gut-microbiota-composition-from-birth-to-24-weeks-in-the-infantmet-cohort
#13
Cian J Hill, Denise B Lynch, Kiera Murphy, Marynka Ulaszewska, Ian B Jeffery, Carol Anne O'Shea, Claire Watkins, Eugene Dempsey, Fulvio Mattivi, Kieran Touhy, R Paul Ross, C Anthony Ryan, Paul W O' Toole, Catherine Stanton
BACKGROUND: The gut is the most extensively studied niche of the human microbiome. The aim of this study was to characterise the initial gut microbiota development of a cohort of breastfed infants (n = 192) from 1 to 24 weeks of age. METHODS: V4-V5 region 16S rRNA amplicon Illumina sequencing and, in parallel, bacteriological culture. The metabolomic profile of infant urine at 4 weeks of age was also examined by LC-MS. RESULTS: Full-term (FT), spontaneous vaginally delivered (SVD) infants' microbiota remained stable at both phylum and genus levels during the 24-week period examined...
January 17, 2017: Microbiome
https://www.readbyqxmd.com/read/28094896/characterisation-of-glufosinate-resistance-mechanisms-in-eleusine-indica
#14
Adam Jalaludin, Qin Yu, Peter Zoellner, Roland Beffa, Stephen B Powles
BACKGROUND: An Eleusine indica population has evolved resistance to glufosinate, a major post-emergence herbicide of global agriculture. This population was analysed for target-site (glutamine synthetase) and non-target-site (glufosinate uptake, translocation and metabolism) resistance mechanisms. RESULTS: Glutamine synthetase (GS) activity extracted from susceptible (S) and resistant (R*) plants was equally sensitive to glufosinate inhibition, with IC50 values of 0...
January 17, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28094519/targeted-multiresidue-analysis-of-veterinary-drugs-in-milk-based-powders-using-liquid-chromatography-tandem-mass-spectrometry-lc-ms-ms
#15
James B Wittenberg, Kelli A Simon, Jon W Wong
An analytical method was developed and validated for the determination of 40 veterinary drugs in various milk-based powders. The method involves acetonitrile/water extraction, solid-phase filtration for lipid removal in fat-containing matrices, and analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS). The limits of quantitation (LOQ) ranged from 0.02 to 82 ng/g. Acceptable recoveries (70-120%, RSD < 20%) were reached for 40 out of 52 target compounds at three fortification levels in non-fat milk powder...
January 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28094300/sequestration-of-prmt1-and-nd1-l-mrna-into-als-linked-fus-mutant-r521c-positive-aggregates-contributes-to-neurite-degeneration-upon-oxidative-stress
#16
Mi-Hee Jun, Hyun-Hee Ryu, Yong-Woo Jun, Tongtong Liu, Yan Li, Chae-Seok Lim, Yong-Seok Lee, Bong-Kiun Kaang, Deok-Jin Jang, Jin-A Lee
Mutations in fused in sarcoma (FUS), a DNA/RNA binding protein, are associated with familial amyotrophic lateral sclerosis (ALS). However, little is known about how ALS-causing mutations alter protein-protein and protein-RNA complexes and contribute to neurodegeneration. In this study, we identified protein arginine methyltransferase 1 (PRMT1) as a protein that more avidly associates with ALS-linked FUS-R521C than with FUS-WT (wild type) or FUS-P525L using co-immunoprecipitation and LC-MS analysis. Abnormal association between FUS-R521C and PRMT1 requires RNA, but not methyltransferase activity...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094153/development-and-validation-of-a-fast-ionic-liquid-based-dispersive-liquid-liquid-microextraction-procedure-combined-with-lc-ms-ms-analysis-for-the-quantification-of-benzodiazepines-and-benzodiazepine-like-hypnotics-in-whole-blood
#17
Marieke De Boeck, Sophie Missotten, Wim Dehaen, Jan Tytgat, Eva Cuypers
To date, thorough clean-up of complex biological samples remains an essential part of the analytical process. The solid phase extraction (SPE) technique is the well-known standard, however, its main weaknesses are the labor-intensive and time-consuming protocols. In this respect, dispersive liquid-liquid microextractions (DLLME) seem to offer less complex and more efficient extraction procedures. Furthermore, ionic liquids (ILs) - liquid salts - are emerging as new promising extraction solvents, thanks to their non-flammable nature, negligible vapor pressure and easily adaptable physiochemical properties...
December 26, 2016: Forensic Science International
https://www.readbyqxmd.com/read/28093968/quantification-of-etodolac-in-human-plasma-for-pharmacokinetics-and-bioequivalence-studies-in-27-korean-subjects
#18
Il-Dong Song, Je-Seop Kang, Hyun-Jin Kim, Se-Mi Kim, Dong-Xu Zhao, Shin-Hee Kim, Min-Young Chun, Kyuhyun Lee
We developed a simple and validated liquid chromatography tandem mass spectrometry(LC-MS/MS) for quantification of etodolac using pioglitazone as an internal standard (IS) to assess pharmacokinetics and to appraise bioequivalence of two formulations of etodolac (reference and tested) in 27 healthy Korean subjects. Isocratic mobile phase consisted of 10 mM ammonium formate and acetonitrile were used to separate the analytes on a Gemini C18 column. Also, analytes were analyzed by MS/MS in multiple reaction monitoring (MRM) mode using the transitions of (M+H)+ ions, m/z 288...
January 16, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/28093289/r-and-s-warfarin-were-transported-by-breast-cancer-resistance-protein-from-in-vitro-to-pharmacokinetic-pharmacodynamic-studies
#19
Meng-Syuan Yang, Chung-Ping Yu, Pei-Dawn Lee Chao, Shiuan-Pey Lin, Yu-Chi Hou
Warfarin, a racemate of R- and S-warfarin, is an important oral anticoagulant with narrow therapeutic window. Being an acidic drug, warfarin (pKa = 4.94) exists mainly as anion under physiological pH. We hypothesized that the transport of warfarin anion across cell membrane was mediated by breast cancer resistance protein (BCRP), an efflux transporter having a variety of acidic substrates. This study aimed to verify that warfarin was a substrate of BCRP. Cell lines and mice were used for transport assay and pharmacokinetic/pharmacodynamic studies, respectively...
January 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28093124/the-co-feature-ratio-a-novel-method-for-the-measurement-of-chromatographic-and-signal-selectivity-in-lc-ms-based-metabolomics
#20
Albert Elmsjö, Jakob Haglöf, Mikael K R Engskog, Marika Nestor, Torbjörn Arvidsson, Curt Pettersson
Evaluation of analytical procedures, especially in regards to measuring chromatographic and signal selectivity, is highly challenging in untargeted metabolomics. The aim of this study was to suggest a new straightforward approach for a systematic examination of chromatographic and signal selectivity in LC-MS-based metabolomics. By calculating the ratio between each feature and its co-eluting features (the co-features), a measurement of the chromatographic selectivity (i.e. extent of co-elution) as well as the signal selectivity (e...
March 1, 2017: Analytica Chimica Acta
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