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https://www.readbyqxmd.com/read/28624482/nmr-quantification-of-trimethylamine-n-oxide-in-human-serum-and-plasma-in-the-clinical-laboratory-setting
#1
Erwin Garcia, Justyna Wolak-Dinsmore, Zeneng Wang, Xinmin S Li, Dennis W Bennett, Margery A Connelly, James D Otvos, Stanley L Hazen, Elias J Jeyarajah
BACKGROUND AND OBJECTIVES: Trimethylamine-N-oxide (TMAO) produced by gut microbiota metabolism of dietary choline and carnitine has been shown to be associated with increased risk of cardiovascular disease (CVD) and to provide incremental clinical prognostic utility beyond traditional risk factors for assessing a patient's CVD risk. The aim of this study was to develop an automated nuclear magnetic resonance (NMR) spectroscopy assay for quantification of TMAO concentration in serum and plasma using a high-throughput NMR clinical analyzer...
June 14, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28623087/highly-multiplex-real-time-pcr-based-screening-for-blood-borne-pathogens-on-an-openarray-platform
#2
Elena Grigorenko, Carolyn Fisher, Sunali Patel, Valerie Winkelman, Phillip Williamson, Caren Chancey, Germán Añez, Maria Rios, Victoria Majam, Sanjai Kumar, Robert Duncan
Molecular diagnostics are increasingly used in the blood bank industry. A device that can combine simultaneous detection of multiple targets with the flexibility of inclusion of emerging pathogens is desirable for testing blood products. A highly multiplexed blood-borne pathogen panel (BBPP) using dual-label probe chemistry (TaqMan assays) was developed for simultaneous detection and discrimination of 17 viral pathogens in human plasma samples and 13 bacterial and protozoan pathogens in human blood samples on the OpenArray platform...
June 12, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28603416/successful-in-vivo-hyperthermal-therapy-toward-breast-cancer-by-chinese-medicine-shikonin-loaded-thermosensitive-micelle
#3
Yonghua Su, Nian Huang, Di Chen, Li Zhang, Xia Dong, Yun Sun, Xiandi Zhu, Fulei Zhang, Jie Gao, Ying Wang, Kexing Fan, Puichi Lo, Wei Li, Changquan Ling
The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28598594/tethering-growth-factors-to-collagen-surfaces-using-copper-free-click-chemistry-surface-characterization-and-in-vitro-biological-response
#4
Hyun Jong Lee, Gabriella Fernandes-Cunha, Ilham Putra, Won-Gun Koh, David Myung
Surface modifications with tethered growth factors have mainly been applied to synthetic polymeric biomaterials in well-controlled, acellular settings, followed by seeding with cells. The known bio-orthogonality of copper-free click chemistry provides an opportunity to not only use it in vitro to create scaffolds or pro-migratory tracks in the presence of living cells, but also potentially apply it to living tissues directly as a coupling modality in situ. In this study, we studied the chemical coupling of growth factors to collagen using biocompatible copper-free click chemistry and its effect on the enhancement of growth factor activity in vitro...
June 9, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28594875/analytical-evaluation-of-three-enzymatic-assays-for-measuring-total-bile-acids-in-plasma-using-a-fully-automated-clinical-chemistry-platform
#5
Elisa Danese, Gian Luca Salvagno, Davide Negrini, Giorgio Brocco, Martina Montagnana, Giuseppe Lippi
BACKGROUND: Although the clinical significance of measuring bile acids concentration in plasma or serum has been recognized for long in patients with hepatobiliary disease and/or bile acid malabsorption, the reference separation techniques are expensive and mostly unsuitable for early diagnosis and for measuring large volumes of samples. Therefore, this study was aimed to evaluate the analytical performance of three commercial enzymatic techniques for measuring total bile acids in plasma using a fully-automated clinical chemistry platform...
2017: PloS One
https://www.readbyqxmd.com/read/28584208/establishment-of-a-novel-method-for-screening-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-resistance-mutations-in-lung-cancer
#6
Hong-Xia Tian, Xu-Chao Zhang, Zhen Wang, Jin-Ji Yang, Wei-Bang Guo, Zhi-Hong Chen, Yi-Long Wu
BACKGROUND: Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform...
June 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28583666/safety-evaluation-of-water-soluble-palm-fruit-bioactives
#7
Barry S Lynch, Spencer West, Ashley Roberts
Water-soluble palm fruit bioactives, derived from the aqueous stream of palm oil processing, have shown anti-diabetogenic effects in rodent models. To assess the safety of potential incorporation of this polyphenol-containing material in food, in vitro bacterial reverse mutation and in vitro chromosome aberration assays were conducted along with a 90-day subchronic toxicity study in Sprague-Dawley rats. Water-soluble palm fruit bioactives were inactive in the Ames and in vitro chromosome aberration assays up to the limit doses of 5000 μg/plate and 5000 μg/mL, respectively...
June 2, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28558755/evaluation-of-a-species-specific-c-reactive-protein-assay-for-the-dog-on-the-abx-pentra-400-clinical-chemistry-analyzer
#8
Sarah Hindenberg, Stefanie Klenner-Gastreich, Nicole Kneier, Sabine Zielinsky, Kris Gommeren, Natali Bauer, Andreas Moritz
BACKGROUND: A canine-specific immunoturbidimetric CRP assay, Gentian Canine CRP Immunoassay) with species-specific controls and calibrators was introduced and recently evaluated on the clinical chemistry analyzer Abbott Architect c4000 as well as on the Olympus AU600. Aims of our study were 1) to independently evaluate the canine-specific CRP assay on the ABX Pentra 400 clinical chemistry analyzer in comparison to the previously validated human-based immunoturbidimetric assay (Randox Canine CRP assay) and 2) to assess the impact of different sample types (serum versus heparinized plasma) on the results...
May 30, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28535882/versatile-fabrication-of-paper-based-microfluidic-devices-with-high-chemical-resistance-using-scholar-glue-and-magnetic-masks
#9
Thiago M G Cardoso, Fabrício R de Souza, Paulo T Garcia, Denilson Rabelo, Charles S Henry, Wendell K T Coltro
Simple methods have been developed for fabricating microfluidic paper-based analytical devices (μPADs) but few of these devices can be used with organic solvents and/or aqueous solutions containing surfactants. This study describes a simple fabrication strategy for μPADs that uses readily available scholar glue to create the hydrophobic flow barriers that are resistant to surfactants and organic solvents. Microfluidic structures were defined by magnetic masks designed with either neodymium magnets or magnetic sheets to define the patter, and structures were created by spraying an aqueous solution of glue on the paper surface...
June 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28526088/assessment-of-parasitological-findings-in-heartworm-infected-beagles-treated-with-advantage-multi%C3%A2-for-dogs-10-imidacloprid%C3%A2-%C3%A2-2-5-moxidectin-and-doxycycline
#10
Molly D Savadelis, Cameon M Ohmes, Joe A Hostetler, Terry L Settje, Robert Zolynas, Michael T Dzimianski, Andrew R Moorhead
BACKGROUND: Anecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles...
May 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28522334/safety-evaluation-of-chlorella-sorokiniana-strain-ck-22-based-on-an-in%C3%A2-vitro-cytotoxicity-assay-and-a-13-week-subchronic-toxicity-trial-in-rats
#11
Sayaka Himuro, Sugi Ueno, Naoto Noguchi, Takuya Uchikawa, Toshihiro Kanno, Akira Yasutake
The genus Chlorella contains unicellular green algae that have been used as food supplements. The purpose of this work was to evaluate the safety of the Chlorella sorokiniana strain CK-22 using powdered preparation (CK-22P) both by in vitro and in vivo assays. These included an experiment for cytotoxicity using Chinese hamster lung fibroblasts (V79 cells) and a 13-week repeated-dose oral toxicity trial using Wistar rats. The cytotoxicity was evaluated by MTT assay of a hot water extract (Hw-Ex) and 80% ethanol extract (Et-Ex) of CK-22P, and no effect on cell viability was observed...
May 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28521765/inhibition-of-o-glcnacase-leads-to-elevation-of-o-glcnac-tau-and-reduction-of-tauopathy-and-cerebrospinal-fluid-tau-in-rtg4510-mice
#12
Nicholas B Hastings, Xiaohai Wang, Lixin Song, Brent D Butts, Diane Grotz, Richard Hargreaves, J Fred Hess, Kwok-Lam Karen Hong, Cathy Ruey-Ruey Huang, Lynn Hyde, Maureen Laverty, Julie Lee, Diane Levitan, Sherry X Lu, Maureen Maguire, Veeravan Mahadomrongkul, Ernest J McEachern, Xuesong Ouyang, Thomas W Rosahl, Harold Selnick, Michaela Stanton, Giuseppe Terracina, David J Vocadlo, Ganfeng Wang, Joseph L Duffy, Eric M Parker, Lili Zhang
BACKGROUND: Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative tauopathies. O-GlcNAcylation is a lesser known post-translational modification of tau that involves the addition of N-acetylglucosamine onto serine and threonine residues. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for the removal of O-GlcNAc modification, has been shown to reduce tau pathology in several transgenic models...
May 18, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28498658/discovery-of-clinical-candidate-1-2s-3s-4s-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl-methoxy-7-methoxyisoquinoline-6-carboxamide-pf-06650833-a-potent-selective-inhibitor-of-interleukin-1-receptor-associated-kinase-4-irak4-by-fragment-based-drug-design
#13
Katherine L Lee, Catherine M Ambler, David R Anderson, Brian P Boscoe, Andrea G Bree, Joanne I Brodfuehrer, Jeanne S Chang, Chulho Choi, Seungwon Chung, Kevin J Curran, Jacqueline E Day, Christoph M Dehnhardt, Ken Dower, Susan E Drozda, Richard K Frisbie, Lori K Gavrin, Joel A Goldberg, Seungil Han, Martin Hegen, David Hepworth, Heidi R Hope, Satwik Kamtekar, Iain C Kilty, Arthur Lee, Lih-Ling Lin, Frank E Lovering, Michael D Lowe, John P Mathias, Heidi M Morgan, Elizabeth A Murphy, Nikolaos Papaioannou, Akshay Patny, Betsy S Pierce, Vikram R Rao, Eddine Saiah, Ivan J Samardjiev, Brian M Samas, Marina W H Shen, Julia H Shin, Holly H Soutter, Joseph W Strohbach, Peter T Symanowicz, Jennifer R Thomason, John D Trzupek, Richard Vargas, Fabien Vincent, Jiangli Yan, Christoph W Zapf, Stephen W Wright
Through fragment-based drug design focused on engaging the active site of IRAK4 and leveraging three-dimensional topology in a ligand-efficient manner, a micromolar hit identified from a screen of a Pfizer fragment library was optimized to afford IRAK4 inhibitors with nanomolar potency in cellular assays. The medicinal chemistry effort featured the judicious placement of lipophilicity, informed by co-crystal structures with IRAK4 and optimization of ADME properties to deliver clinical candidate PF-06650833 (compound 40)...
June 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28494633/comparison-of-in-clinic-point-of-care-and-reference-laboratory-total-thyroxine-immunoassays-for-diagnosis-and-post-treatment-monitoring-of-hyperthyroid-cats
#14
Mark E Peterson, Mark Rishniw, Graham E Bilbrough, Kate B Cote
Objectives The Catalyst One Chemistry Analyzer (IDEXX Laboratories) is a point-of-care instrument that can measure total thyroxine (TT4) by immunoassay. The aims of this study were to evaluate the analytic performance of the Catalyst TT4 assay in feline sera and to examine agreement of the Catalyst TT4 results with those measured by immunoassay at a veterinary reference laboratory. Methods Assay precision, reproducibility and linearity were evaluated for the Catalyst TT4 assay. For method comparison, TT4 concentrations in serum samples from 157 cats (127 hyperthyroid, 30 radioiodine-treated cats) were analyzed by both in-clinic and reference laboratory methods...
May 1, 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28490046/rapid-homogeneous-immunoassay-to-quantify-gemcitabine-in-plasma-for-therapeutic-drug-monitoring
#15
Daniel Kozo, Matt W Ross, Justin Jarrah, Michael Barrett, Rebecca L Harney, Jodi B Courtney, Irina Baburina, Julianne L Holleran, Jan H Beumer, Godefridus J Peters, Richard J Honeywell, Salvatore J Salamone
BACKGROUND: Gemcitabine (2',2'-difluoro-2'-deoxycytidine) is a nucleoside analog used as a single agent and in combination regimens for the treatment of a variety of solid tumors. Several studies have shown a relationship between gemcitabine peak plasma concentration (Cmax) and hematological toxicity. An immunoassay for gemcitabine in plasma was developed and validated to facilitate therapeutic drug monitoring (TDM) by providing an economical, robust method for automated chemistry analyzers...
June 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28487066/genotoxicity-acute-and-subchronic-toxicity-evaluation-of-savory-food-ingredients
#16
Shahrzad Tafazoli, Trung D Vo, Anne Petersen, Anne Constable, Myriam Coulet, Phoukham Phothirath, Johanna Lang, Nigel Baldwin
The potential toxicity of two savory food ingredients produced by fermentation of enzymatically hydrolyzed corn starch (Savory Base 100 and Savory Base 200) was evaluated individually in a bacterial reverse mutation assay, an in vitro mammalian cell gene mutation assay, an acute oral study and as a mixture in a 90-day dietary study. In the bacterial reverse mutation and in vitro mammalian cell gene mutation assays, neither ingredient was mutagenic at concentrations up to 5000 μg/plate and 5000 μg/mL, respectively in the presence and absence of metabolic activation...
May 6, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28458688/long-term-safety-of-pegylated-coagulation-factor-viii-in-the-immune-deficient-rowett-nude-rat
#17
Caroline E Rasmussen, Jette Nowak, Julie M Larsen, Emma Moore, David Bell, Kai Chiu Liu, Nanna Skall Sorensen, Wendela A Kappers, Thomas Krogh-Meibom, Hanne Offenberg
Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP...
2017: Journal of Toxicology
https://www.readbyqxmd.com/read/28456543/subchronic-toxicity-of-low-dose-propoxur-permethrin-and-their-combination-on-the-redox-status-of-rat-liver
#18
Pan Wang, Ming-Yuan Xu, Yu-Jie Liang, Hui-Ping Wang, Ying-Jian Sun, Ding-Xin Long, Yi-Jun Wu
Carbamates and pyrethroids are widely used pesticides. However, their joint toxicity at low doses with long-term exposure remains unknown. Therefore, we investigated the subchronic joint hepatotoxicity of the two representative pesticides within these two classes, i.e., propoxur (PR) and permethrin (PE) in rats. The male Wistar rats were orally treated with three different doses of PR, PE and their mixtures for 90 consecutive days. Liver weight, serum clinical chemistry parameters and histopathological changes were measured to access the hepatotoxicity...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28442262/an-integrated-chemical-biology-approach-reveals-the-mechanism-of-action-of-hiv-replication-inhibitors
#19
Nicholas Pagano, Peter Teriete, Margrith E Mattmann, Li Yang, Beth A Snyder, Zhaohui Cai, Marintha L Heil, Nicholas D P Cosford
Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP)...
April 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28428356/biological-variation-estimates-obtained-from-91-healthy-study-participants-for-9-enzymes-in-serum
#20
Anna Carobene, Thomas Røraas, Una Ørvim Sølvik, Marit Sverresdotter Sylte, Sverre Sandberg, Elena Guerra, Irene Marino, Niels Jonker, Gerhard Barla, William A Bartlett, Pilar Fernandez-Calle, Jorge Díaz-Garzón, Francesca Tosato, Mario Plebani, Abdurrahman Coŝkun, Mustafa Serteser, Ibrahim Unsal, Ferruccio Ceriotti
BACKGROUND: We sought to develop estimates of biological variation (BV) for 9 enzymes in blood serum as part of the European Biological Variation Study. METHODS: Ninety-one healthy study participants (38 male and 53 female, 21-69 years old) were phlebotomized in each of 10 consecutive weeks at 6 European laboratories. The same preanalytical sample-handling protocol was followed at each center before transport to San Raffaele Hospital, Milan, Italy, for analysis...
April 20, 2017: Clinical Chemistry
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