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https://www.readbyqxmd.com/read/28822784/a-novel-model-for-the-pharmacokinetic-studies-of-bevacizumab-and-etanercept-in-healthy-volunteers-and-patients
#1
Meizhen Li, Wei Qiang, Li Hu, Lei Wang, Zeneng Cheng
Therapeutic monoclonal antibodies (mAbs) have been successfully applied to treat various diseases and shown a promising prospect in medical treatment. MAbs have some unique characteristics comparing with small chemical drugs, and their pharmacokinetic (PK) properties are much more complex than those of small chemical drugs, whose eliminations are usually linear. In this study, a new model was established through taking into account the mechanisms of the elimination of mAbs. The proposed model was applied to the modeling and simulation of two kinds of mAbs, including bevacizumab and etanercept, in PK studies of healthy volunteers and eligible patients, and the classical linear compartment model was set as control...
August 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28822278/a-carbon-tetrachloride-free-synthesis-of-n-phenyltrifluoroacetimidoyl-chloride
#2
Dylan G M Smith, Spencer J Williams
N-Phenyltrifluoroacetimidoyl chloride (PTFAI-Cl) is a reagent widely used for the preparation of glycosyl N-phenyltrifluoroacetimidates. However, the most commonly applied method requires carbon tetrachloride, a hepatotoxic reagent that has been phased out under the Montreal Protocol. We report a new synthesis of N-phenyltrifluoroacetimidoyl chloride (PTFAI-Cl) using dichlorotriphenylphosphane and triethylamine.
August 10, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28821638/fluorescent-probes-for-selective-protein-labeling-in-lysosomes-a-case-of-%C3%AE-galactosidase-a
#3
Cornelius Bohl, Adam Pomorski, Susanne Seemann, Anne-Marie Knospe, Chaonan Zheng, Artur Krężel, Arndt Rolfs, Jan Lukas
Fluorescence-based live-cell imaging (LCI) of lysosomal glycosidases is often hampered by unfavorable pH and redox conditions that reduce fluorescence output. Moreover, most lysosomal glycosidases are low-mass soluble proteins that do not allow for bulky fluorescent protein fusions. We selected α-galactosidase A (GALA) as a model lysosomal glycosidase involved in Anderson-Fabry disease (AFD) for the current LCI approach. Examination of the subcellular localization of AFD-causing mutants can reveal the mechanism underlying cellular trafficking deficits...
August 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821460/long-term-effects-of-hydrogen-sulfide-on-the-anabolic-catabolic-balance-of-articular-cartilage-in-vitro
#4
A Vela-Anero, T Hermida-Gomez, L Gato-Calvo, C Vaamonde-García, S Diaz-Prado, R Meijide-Faílde, F J Blanco, E F Burguera
Healthy cartilage maintenance relies on an equilibrium among the anabolic and catabolic processes in chondrocytes. With the onset of osteoarthritis (OA), increased interleukin (IL)-1β levels induce an inhibition of the synthesis of extracellular matrix (ECM) proteins, as well as an increase in proteases. This eventually leads to a predominance of the catabolic phenotype and the progressive loss of articular cartilage. Hydrogen sulfide (H2S) is a small gaseous molecule recognized as the third endogenous gasotransmitter...
August 15, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28821247/a-cost-effective-approach-to-produce-15-n-labelled-amino-acids-employing-chlamydomonas-reinhardtii-cc503
#5
Jesús Nicolás Carcelén, Juan Manuel Marchante-Gayón, Pablo Rodríguez González, Luis Valledor, María Jesús Cañal, José Ignacio García Alonso
BACKGROUND: The use of enriched stable isotopes is of outstanding importance in chemical metrology as it allows the application of isotope dilution mass spectrometry (IDMS). Primary methods based on IDMS ensure the quality of the analytical measurements and traceability of the results to the international system of units. However, the synthesis of isotopically labelled molecules from enriched stable isotopes is an expensive and a difficult task. Either chemical and biochemical methods to produce labelled molecules have been proposed, but so far, few cost-effective methods have been described...
August 18, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28820977/a-newly-validated-and-characterized-spectrophotometric-method-for-determination-of-a-three-water-pollutants-metal-ions
#6
Marwa E Mohamed, Eman Y Z Frag, Mona A Mohamed
A simple, fast and accurate spectrophotometric method had been developed to determine lead (II), chromium (III) and barium (II) ions in pure forms and in spiked water samples using thoron (THO) as a reagent forming colored complexes. It was found that the formed complexes absorbed maximally at 539, 540 and 538nm for Pb(II)-THO, Cr(III)-THO and Ba(II)-THO complexes, respectively. The optimum experimental conditions for these complexes had been studied carefully. Beer's law was obeyed in the range 1-35, 1-70, and 1-45μgmL(-1) for Pb (II), Cr(III) and Ba(II) ions with THO reagent, respectively...
August 9, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28820953/a-fluorescence-based-high-throughput-assay-for-the-identification-of-anticancer-reagents-targeting-fructose-1-6-bisphosphate-aldolase
#7
Eun Jeong Cho, Ashwini K Devkota, Gabriel Stancu, Ramakrishna Edupunganti, Garth Powis, Kevin N Dalby
A high rate of glycolysis, which supplies energy and materials for anabolism, is observed in a wide range of tumor cells, making it a potential pathway to control cancer growth. ALDOA is a multifunctional enzyme in the glycolytic pathway and also promotes HIF-1α, which is of importance in hypoxic solid tumors. The current method for assaying ALDOA activity involves monitoring the consumption of NADH in vitro using absorbance or intrinsic fluorescence via a coupled enzymatic reaction. Here, we report the development of a homogeneous biochemical assay that can overcome limitations of current methods, in particular for the application of high-throughput drug screening...
August 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28820431/high-throughput-screening-assay-for-laccase-engineering-toward-lignosulfonate-valorization
#8
David Rodríguez-Escribano, Felipe de Salas, Isabel Pardo, Susana Camarero
Lignin valorization is a pending issue for the integrated conversion of lignocellulose in consumer goods. Lignosulfonates (LS) are the main technical lignins commercialized today. However, their molecular weight should be enlarged to meet application requirements as additives or dispersing agents. Oxidation of lignosulfonates with fungal oxidoreductases, such as laccases, can increase the molecular weight of lignosulfonates by the cross-linking of lignin phenols. To advance in this direction, we describe here the development of a high-throughput screening (HTS) assay for the directed evolution of laccases, with lignosulfonate as substrate and the Folin-Ciocalteau reagent (FCR), to detect the decrease in phenolic content produced upon polymerization of lignosulfonate by the enzyme...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28820258/transition-metal-free-trifluoromethylation-of-aldehyde-derivatives-with-sodium-trifluoromethanesulfinate
#9
Zheng Tan, Shiwei Zhang, Yan Zhang, Yunpeng Li, Minjie Ni, Bainian Feng
A metal-free and cost-effective synthetic protocol for trifluoromethylation of N,N-disubstitutedhydrazones with Langlois' reagent (CF3SO2Na) to afford the corresponding functionalized trifluoromethylketone hydrazones has been established. It is proposed that a radical/SET mechanism proceeding via a trifluoroalkyl radical may be involved in the reaction. Applications of the methodology in industry will be found and the development of new methods for trifluoromethylation with Langlois' reagent will be continued in our laboratory...
August 18, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28820204/droplet-microfluidics-for-synthetic-biology
#10
REVIEW
Philip C Gach, Kosuke Iwai, Peter W Kim, Nathan J Hillson, Anup K Singh
Synthetic biology is an interdisciplinary field that aims to engineer biological systems for useful purposes. Organism engineering often requires the optimization of individual genes and/or entire biological pathways (consisting of multiple genes). Advances in DNA sequencing and synthesis have recently begun to enable the possibility of evaluating thousands of gene variants and hundreds of thousands of gene combinations. However, such large-scale optimization experiments remain cost-prohibitive to researchers following traditional molecular biology practices, which are frequently labor-intensive and suffer from poor reproducibility...
August 18, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28819973/mobile-platform-for-multiplexed-detection-and-differentiation-of-disease-specific-nucleic-acid-sequences-using-microfluidic-loop-mediated-isothermal-amplification-and-smartphone-detection
#11
Weili Chen, Hojeong Yu, Fu Sun, Akid Ornob, Ryan Brisbin, Anurup Ganguli, Vinay Kumar Vemuri, Piotr Strzebonski, Guangzhe Cui, Karen J Allen, Smit A Desai, Weiran Lin, David M Nash, David Hirschberg, Ian Brooks, Rashid Bashir, Brian T Cunningham
New tools are needed to enable rapid detection, identification, and reporting of infectious viral and microbial pathogens in a wide variety of point-of-care applications that impact human and animal health. We report the design, construction, and characterization of a platform for multiplexed analysis of disease-specific DNA sequences that utilizes a smartphone camera as the sensor in conjunction with a handheld "cradle" that interfaces the phone with a silicon-based microfluidic chip embedded within a credit card-sized cartridge...
August 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#12
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but in some cases also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
August 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28817776/electrophilic-cyclization-of-phenylalkynediols-to-naphthyl-aryl-iodonium-triflates-with-chelating-hydroxyls-preparation-and-x-ray-analyses
#13
Robert James Hinkle, Sarah E Bredenkamp, Robert David Pike, Seong Ik Cheon
Alkynediols containing one propargylic alcohol as well as a second alcohol, which is propargylic or homopropargylic, react with PhI(+)CN(-)OTf (Stang's reagent) or 3,5-(CF3)2C6H3I(+)CN(-)OTf to afford naphthyl(aryl)iodonium triflates. The reaction occurs at room temperature over the course of 6-12 hours and provides 36-82% yields of microcrystalline solids. Slow diffusion of Et2O into CH3CN solutions of the salts afforded X-ray quality crystals of five compounds with hydroxyl groups forming five- and six-membered chelation complexes with the iodine atom...
August 17, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28817768/metal-free-synthesis-of-homopropargylic-alcohols-from-aldehydes
#14
Bruno V M Teodoro, Luiz F Silva
The synthesis of homopropargylic alcohols under metal-free and mild condition is described. This transformation is based on a one-pot procedure involving sequential α-alkynylation of acyclic aldehydes using hypervalent iodine reagents and borohydride reduction. The chemistry exhibit broad substrate scope and good scalability, providing a convenient route for the α-alkynylation of aldehydes along with the formation of a quaternary carbon center. The applicability of the method is demonstrated by the gram-scale synthesis of the key synthetic precursor of botulinum toxin inhibitors...
August 17, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28817685/clinical-implications-of-carcinoembryonic-antigen-distribution-in-serum-exosomal-fraction-measurement-by-elisa
#15
Shozo Yokoyama, Akihiro Takeuchi, Shunsuke Yamaguchi, Yasuyuki Mitani, Takashi Watanabe, Kenji Matsuda, Tsukasa Hotta, John E Shively, Hiroki Yamaue
BACKGROUND: Serum exosomal proteins have great potential as indicators of disease status in cancer, inflammatory or metabolic diseases. The association of a fraction of various serum proteins such as carcinoembryonic antigen (CEA) with circulating exosomes has been debated. The establishment of a method to measure the exosomal fraction of such proteins might help resolve this controversy. The use of enzyme-linked immunosorbent assays (ELISAs) to measure serum exosomal molecules, for example CEA, is rare in research laboratories and totally absent in clinical biology...
2017: PloS One
https://www.readbyqxmd.com/read/28817121/meganuclease-assisted-generation-of-stable-transgenics-in-the-sea-anemone-nematostella-vectensis
#16
Eduard Renfer, Ulrich Technau
The sea anemone Nematostella vectensis is a model system used by a rapidly growing research community for comparative genomics, developmental biology and ecology. Here, we describe a microinjection procedure for creating stable transgenic lines in Nematostella based on meganuclease (I-SceI)-assisted integration of a transgenic cassette into the genome. The procedure describes the preparation of the reagents, microinjection of the transgenesis vector and the husbandry of transgenic animals. The microinjection setup differs from those of previously published protocols by the use of a holding capillary mounted on an inverted fluorescence microscope...
September 2017: Nature Protocols
https://www.readbyqxmd.com/read/28817110/extractive-spectrophotometric-determination-of-nortriptyline-hydrochloride-using-sudan-ii-iv-and-black-b
#17
A S Amin, H M Saleh
A simple spectrophotometric methods has been developed for the determination of nortriptyline hydrochloride in pure and in pharmaceuticalformulations based on the formation of ion-pair complexes with sudun II (SII), sudan (IV) (SIV) and sudan black B (SBB). The selectivity of the method was improved through extraction with chloroform. The optimum conditions for complete extracted colour development were assessed. The absorbance measurements were made at 534, 596 and 649 nm for SII, SIV and SBB complexes, respectively...
August 17, 2017: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28816448/metal-free-oxidative-c-c-coupling-of-arylamines-using-a-quinone-based-organic-oxidant
#18
Sudhakar Maddala, Sudesh Mallick, Parthasarathy Venkatakrishnan
A variety of arylamines are shown to undergo oxidative C-C bond formation using quinone-based chloranil/H(+) reagent as the recyclable organic (metal-free) oxidant system to afford benzidines/naphthidines. Arylamines (3°/2°) designed with various substituents were employed to understand the steric as well as electronic preferences of oxidative dimerization, and a mechanism involving amine radical cation has been proposed. The tetraphenylbenzidine derivative obtained via oxidative C-C coupling has been further converted to blue-emissive hole-transporting material via a simple chemical transformation...
August 17, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28816444/mapping-the-intricate-reactivity-of-nanojars-toward-molecules-of-varying-acidity-and-their-conjugate-bases-leading-to-exchange-of-pyrazolate-ligands
#19
Christian K Hartman, Gellert Mezei
A comprehensive reactivity study of nanojars toward 18 different acidic compounds with varying pKa, including 12 different carboxylic acids (both aliphatic and aromatic mono- and dicarboxylic acids), p-toluenesulfonic acid, hydrogen sulfate, hydrogen carbonate, carbonic acid, 1-decanethiol, and methanol, as well as four different conjugate bases (formate, acetate, benzoate, 2-bromoethanesulfonate) is carried out with the aid of electrospray-ionization mass spectrometry. Thus, the effect on nanojar substitution and breakdown pattern of a number of variables, such as concentration of reagent (acid or conjugate base), acidity of reagent (pKa), effect of acid vs conjugate base, steric effects, aromaticity, incarcerated anion and size of the nanojar, is evaluated...
August 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28816440/high-quantities-of-microplastic-in-arctic-deep-sea-sediments-from-the-hausgarten-observatory
#20
Melanie Bergmann, Vanessa Wirzberger, Thomas Krumpen, Claudia Lorenz, Sebastian Primpke, Mine B Tekman, Gunnar Gerdts
Although mounting evidence suggests the ubiquity of microplastic in aquatic ecosystems worldwide, our knowledge of its distribution in remote environments such as Polar Regions and the deep sea is scarce. Here, we analyzed nine sediment samples taken at the HAUSGARTEN observatory in the Arctic at 2,340 - 5,570 m depth. Density separation by MicroPlastic Sediment Separator and treatment with Fenton's reagent enabled analysis via Attenuated Total Reflection FTIR and µFTIR spectroscopy. Our analyses indicate the wide spread of high numbers of microplastics (42 - 6,595 microplastics kg-1)...
August 17, 2017: Environmental Science & Technology
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