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https://www.readbyqxmd.com/read/27922183/the-significance-of-sampling-time-in-therapeutic-drug-monitoring-of-clozapine
#1
M I Jakobsen, J R Larsen, C K Svensson, S S Johansen, K Linnet, J Nielsen, A Fink-Jensen
OBJECTIVE: Therapeutic drug monitoring (TDM) of clozapine is standardized to 12-h postdose samplings. In clinical settings, sampling time often deviates from this time point, although the importance of the deviation is unknown. To this end, serum concentrations (s-) of clozapine and its metabolite N-desmethyl-clozapine (norclozapine) were measured at 12 ± 1 and 2 h postdose. METHOD: Forty-six patients with a diagnosis of schizophrenia, and on stable clozapine treatment, were enrolled for hourly, venous blood sampling at 10-14 h postdose...
December 6, 2016: Acta Psychiatrica Scandinavica
https://www.readbyqxmd.com/read/27922096/enantiomer-signature-and-carbon-isotope-evidence-for-the-migration-and-transformation-of-ddts-in-arable-soils-across-china
#2
Lili Niu, Chao Xu, Siyu Zhu, Huiming Bao, Yang Xu, Hongyi Li, Zhijian Zhang, Xichang Zhang, Jiguo Qiu, Weiping Liu
Due to the adverse impact of DDTs on ecosystems and humans, a full fate assessment deems a comprehensive study on their occurrence in soils over a large region. Through a sampling campaign across China, we measured the concentrations, enantiomeric fractions (EFs), compound-specific carbon isotope composition of DDT and its metabolites, and the microbial community in related arable soils. The geographically total DDT concentrations are higher in eastern than western China. The EFs and δ(13)C of o,p'-DDT in soils from western China show smaller deviations from those of racemic/standard compound, indicating the DDT residues there mainly result from atmospheric transport...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921460/direct-infusion-mass-spectrometry-for-metabolomic-phenotyping-of-diseases
#3
Raúl González-Domínguez, Ana Sayago, Ángeles Fernández-Recamales
Metabolomics based on direct mass spectrometry (MS) analysis, either by direct infusion or flow injection of crude sample extracts, shows a great potential for metabolic fingerprinting because of its high-throughput screening capability, wide metabolite coverage and reduced time of analysis. Considering that numerous metabolic pathways are significantly perturbed during the initiation and progression of diseases, these metabolomic tools can be used to get a deeper understanding about disease pathogenesis and discover potential biomarkers for early diagnosis...
January 2017: Bioanalysis
https://www.readbyqxmd.com/read/27921459/investigation-of-the-derivatization-conditions-for-gc-ms-metabolomics-of-biological-samples
#4
Georgios Moros, Anastasia Chrysovalantou Chatziioannou, Helen G Gika, Nikolaos Raikos, Georgios Theodoridis
AIM: Metabolomics applications represent an emerging field where significant efforts are directed. Derivatization consists prerequisite for GC-MS metabolomics analysis. METHODS: Common silylation agents were tested for the derivatization of blood plasma. Optimization of methoxyamination and silylation reactions was performed on a mixture of reference standards, consisting of 46 different metabolites. Stability of derivatized metabolites was tested at 4°C. RESULTS: Optimum results were achieved using N-methyl-N-(trimethylsilyl)trifluoroacetamide...
January 2017: Bioanalysis
https://www.readbyqxmd.com/read/27921458/metabolic-profile-of-human-coelomic-fluid
#5
C Virgiliou, L Valianou, M Witting, F Moritz, C Fotakis, P Zoumpoulakis, A C Chatziioannou, L Lazaros, G Makrydimas, K Chatzimeletiou, N Raikos, G A Theodoridis
AIM: Till now there is very limited knowledge on the molecular content of coelomic fluid and cells. This study presents the first attempt to elucidate the metabolic profile of such samples. METHODOLOGY: Samples were collected via coelocentesis from 41 women during the first trimester of gestation. Metabolic content was assessed using four different analytical platforms. For targeted analysis a hydrophilic interaction chromatography ultra high performance LC-MS/MS method was applied...
January 2017: Bioanalysis
https://www.readbyqxmd.com/read/27921456/capillary-electrophoresis-mass-spectrometry-as-a-tool-for-untargeted-metabolomics
#6
Antonia García, Joanna Godzien, Ángeles López-Gonzálvez, Coral Barbas
Highly polar and ionic metabolites, such as sugars, most amino acids, organic acids or nucleotides are not retained by conventional reversed-phase LC columns and polar stationary phases and hydrophilic-interaction LC lacks of robustness, which is still limiting their applications for untargeted metabolomics where reproducibility is a must. Biological samples such as blood, urine or even tissues include many hydrophilic compounds secreted from cells, their analysis is essential for biomarker discovery, disease progression or treatment effects...
January 2017: Bioanalysis
https://www.readbyqxmd.com/read/27921453/integrating-ion-mobility-spectrometry-into-mass-spectrometry-based-exposome-measurements-what-can-it-add-and-how-far-can-it-go
#7
Thomas O Metz, Erin S Baker, Emma L Schymanski, Ryan S Renslow, Dennis G Thomas, Tim J Causon, Ian K Webb, Stephan Hann, Richard D Smith, Justin G Teeguarden
Measuring the exposome remains a challenge due to the range and number of anthropogenic molecules that are encountered in our daily lives, as well as the complex systemic responses to these exposures. One option for improving the coverage, dynamic range and throughput of measurements is to incorporate ion mobility spectrometry (IMS) into current MS-based analytical methods. The implementation of IMS in exposomics studies will lead to more frequent observations of previously undetected chemicals and metabolites...
January 2017: Bioanalysis
https://www.readbyqxmd.com/read/27921366/masked-trichothecene-and-zearalenone-mycotoxins-withstand-digestion-and-absorption-in-the-upper-gi-tract-but-are-efficiently-hydrolyzed-by-human-gut-microbiota-in-vitro
#8
Silvia W Gratz, Reshma Dinesh, Tomoya Yoshinari, Grietje Holtrop, Anthony J Richardson, Gary Duncan, Susan MacDonald, Antony Lloyd, Jonathan Tarbin
SCOPE: Cereal grains are commonly contaminated with Fusarium mycotoxins and their plant-derived masked metabolites. The fate of masked mycotoxins in the human gut is poorly understood. Here we assess the metabolism and transport of glucoside metabolites of common trichothecenes (deoxynivalenol, nivalenol, T-2 toxin) and zearalenone compounds (zearalenone, α- and β-zearalenol) in the human gut in vitro. METHODS AND RESULTS: Masked mycotoxins were incubated with artificial digestive juices and absorption was assessed in differentiated Caco-2/TC7 cells...
December 6, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27921344/uhplc-ms-based-hdac-assay-applied-to-bio-guided-microfractionation-of-fungal-extracts
#9
Vincent Zwick, Pierre-Marie Allard, Lucie Ory, Claudia A Simões-Pires, Laurence Marcourt, Katia Gindro, Jean-Luc Wolfender, Muriel Cuendet
INTRODUCTION: Histone deacetylases (HDAC) are considered as promising targets for cancer treatment. Today, four HDAC inhibitors, vorinostat, romidepsin, belinostat, and panobinostat, have been approved by the Food and Drug Administration (FDA) for cancer treatment, while others are in clinical trials. Among them, several are naturally occurring fungal metabolites. OBJECTIVE: To develop and optimise an enzyme assay for bio-guided identification of HDAC inhibitors in fungal strains...
December 5, 2016: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/27921334/synacton-and-individual-activity-of-synthetic-and-natural-corticotropins
#10
T V Vyunova, L A Andreeva, K V Shevchenko, N F Myasoedov
Short endogenous peptides represent one of the most important constituents of the mammalian body's general regulatory system. Some synthesized analogs and modified natural peptides (eg, corticotropins) also show high biological activity. Nevertheless, the mechanism of action of regulatory peptides remains unclear. To explain the effects of peptides of intermolecular processes, the hypothesis that a synactonal mechanism underlies the action of regulatory peptides, exemplified by the heptapeptide Semax, has been proposed...
December 6, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27921148/metabolites-deciphering-the-molecular-language-between-dcs-and-their-environment
#11
REVIEW
Lucía Minarrieta, Peyman Ghorbani, Tim Sparwasser, Luciana Berod
Dendritic cells (DCs) determine the outcome of the immune response based on signals they receive from the environment. Presentation of antigen under various contexts can lead to activation and differentiation of T cells for immunity or dampening of immune responses by establishing tolerance, primarily through the priming of regulatory T cells. Infections, inflammation and normal cellular interactions shape DC responses through direct contact or via cytokine signaling. Although it is widely accepted that DCs sense microbial components through pattern recognition receptors (PRRs), increasing evidence advocates for the existence of a set of signals that can profoundly shape DC function via PRR-independent pathways...
December 5, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27920977/neurochemical-changes-in-patients-with-chronic-low-back-pain-detected-by-proton-magnetic-resonance-spectroscopy-a-systematic-review
#12
REVIEW
Xianjing Zhao, Maosheng Xu, Kristen Jorgenson, Jian Kong
BACKGROUND: Low back pain is a highly prevalent health problem around the world, affecting 50% to 85% of people at some point in life. The purpose of this systematic review is to summarize the previous proton magnetic resonance spectroscopy studies on brain chemical changes in patients with chronic low back pain (CLBP). METHODS: We identified relevant studies from a literature search of PubMed and EMBASE from 1980 to March 2016. Data extraction was performed on the subjects' characteristics, MRS methods, spectral analyses, cerebral metabolites and perceptual measurements...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27920785/a-jasmonate-inducible-defense-trait-transferred-from-wild-into-cultivated-tomato-establishes-increased-whitefly-resistance-and-reduced-viral-disease-incidence
#13
Rocío Escobar-Bravo, Juan M Alba, Clara Pons, Antonio Granell, Merijn R Kant, Enrique Moriones, Rafael Fernández-Muñoz
Whiteflies damage tomatoes mostly via the viruses they transmit. Cultivated tomatoes lack many of the resistances of their wild relatives. In order to increase protection to its major pest, the whitefly Bemisia tabaci and its transmitted Tomato Yellow Leaf Curl Virus (TYLCV), we introgressed a trichome-based resistance trait from the wild tomato Solanum pimpinellifolium into cultivated tomato, Solanum lycopersicum. The tomato backcross line BC5S2 contains acylsucrose-producing type-IV trichomes, unlike cultivated tomatoes, and exhibits increased, yet limited protection to whiteflies at early development stages...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27920527/pharmacokinetics-and-safety-of-dts-108-a-human-oligopeptide-bound-to-sn-38-with-an-esterase-sensitive-cross-linker-in-patients-with-advanced-malignancies-a-phase-i-study
#14
Romain Coriat, Sandrine J Faivre, Olivier Mir, Chantal Dreyer, Stanislas Ropert, Mohammed Bouattour, Robert Desjardins, François Goldwasser, Eric Raymond
BACKGROUND: DTS-108 is a hydrosoluble prodrug, where the SN-38 moiety is covalently linked to a 20-amino acid vector peptide by a specific esterase-sensitive cross-linker, releasing 7-ethyl-10-hydroxycampthotecin (SN-38) by esterase bond cleavage. METHODS: The pharmacokinetics of DTS-108, adverse events graded according to NCI-CTCv3.1, dose-limiting toxicities at cycle 1, the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of intravenous DTS-108 (1-2 hours) every 2 weeks were evaluated in a first-in-human Phase I study in patients with advanced/metastatic carcinomas, according to an accelerated dose escalation design...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920379/domestication-impacts-on-plant-herbivore-interactions-a-meta-analysis
#15
Susan R Whitehead, Martin M Turcotte, Katja Poveda
For millennia, humans have imposed strong selection on domesticated crops, resulting in drastically altered crop phenotypes compared with wild ancestors. Crop yields have increased, but a long-held hypothesis is that domestication has also unintentionally decreased plant defences against herbivores. To test this hypothesis, we conducted a phylogenetically controlled meta-analysis comparing insect herbivore resistance and putative plant defence traits between crops and their wild relatives. Our database included 2098 comparisons made across 73 crops in 89 studies...
January 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27920202/the-translational-significance-of-the-neurovascular-unit-a-mini-review
#16
Heather L McConnell, Cymon N Kersch, Randall L Woltjer, Edward A Neuwelt
The mammalian brain is supplied with blood by specialized vasculature that is structurally and functionally distinct from that of the periphery. A defining feature of this vasculature is a physical blood-brain barrier (BBB). The BBB separates blood components from the brain microenvironment, regulating the entry and exit of ions, nutrients, macromolecules, and energy metabolites. Over the last two decades, physiological studies of cerebral blood flow dynamics have demonstrated that substantial intercellular communication occurs between cells of the vasculature and the neurons and glia that abut the vasculature...
December 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27919940/vitamin-d-and-myofibroblasts-in-fibrosis-and-cancer-at-cross-purposes-with-tgf-%C3%AE-smad-signaling
#17
REVIEW
Shraga Shany, Ina Sigal-Batikoff, Sergio Lamprecht
The multifaceted involvement of the active vitamin D metabolite 1,25-dihydroxyvitamin D3 (henceforth referred to by the synonyms 1,25(OH)2D3, calcitriol or vitamin D) in blunting the growth of cancer cells is amply recognized. In this review we focused our attention on the cross-talk between 1,25 (OH)2D3 and the tumor microenvironment (TME), signaling out stromal cancer-associated fibroblasts (CAFs), the most abundant TME population, as a target for calcitriol anticancer action. In view of the commonality of the phenotypic signature in myofibroblasts, resident in the cancer stroma and in non-neoplastic fibrotic loci, we examined modes of action of vitamin D in non-neoplastic chronic diseases and in cancer to assess mechanistic similarities and divergences...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919802/integrative-view-of-2-oxoglutarate-fe-ii-dependent-oxygenase-diversity-and-functions-in-bacteria
#18
Baolei Jia, Xiaomeng Jia, Kyung Hyun Kim, Che Ok Jeon
BACKGROUND: The 2-oxoglutarate/Fe(II)-dependent oxygenase (2OG oxygenase) superfamily is extremely diverse and includes enzymes responsible for protein modification, DNA and mRNA repair, and synthesis of secondary metabolites. METHODS: To investigate the evolutionary relationship and make functional inferences within this remarkably diverse superfamily in bacteria, we used a protein sequence similarity network and other bioinformatics tools to analyze the bacterial proteins in the superfamily...
December 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27919791/biosensor-assisted-transcriptional-regulator-engineering-for-methylobacterium-extorquens-am1-to-improve-mevalonate-synthesis-by-increasing-the-acetyl-coa-supply
#19
Wei-Fan Liang, Lan-Yu Cui, Jin-Yu Cui, Kai-Wen Yu, Song Yang, Chong Zhang, Xin-Hui Xing
Acetyl-CoA is not only an important intermediate metabolite for cells but also a significant precursor for production of industrially interesting metabolites. Methylobacterium extorquens AM1, a model strain of methylotrophic cell factories using methanol as carbon source, is of interest because it produces abundant coenzyme A compounds capable of directing to synthesis of different useful compounds from methanol. However, acetyl-CoA always does not efficiently accumulate in M.extorquens AM1, as it is located in the center of three cyclic central metabolic pathways...
December 2, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27919747/h19-mediates-methotrexate-resistance-in-colorectal-cancer-through-activating-wnt-%C3%AE-catenin-pathway
#20
Ke-Feng Wu, Wei-Cheng Liang, Lu Feng, Jian-Xin Pang, Mary Miu-Yee Waye, Jin-Fang Zhang, Wei-Ming Fu
Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. As one of the earliest cytotoxic drugs, methotrexate (MTX) serves as an anti-metabolite and anti-folate chemotherapy for various cancers. Unfortunately, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the therapeutic efficacy of MTX in clinics. Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years...
December 2, 2016: Experimental Cell Research
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