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https://www.readbyqxmd.com/read/28645021/development-a-validated-highly-sensitive-lc-ms-ms-method-for-simultaneous-quantification-of-ledipasvir-sofosbuvir-and-its-major-metabolite-gs-331007-in-human-plasma-application-to-a-human-pharmacokinetic-study
#1
Ola M Abdallah, Ahmed M Abdel-Megied, Amira S Gouda
A highly sensitive and rapid LC-MS/MS method was developed, fully optimized and validated for the simultaneous determination of Ledipasvir (LED) and Sofosbuvir (SOF) in the presence of its major metabolite GS-331007 in human plasma using Daclatasvir as internal standard (IS). The extraction of analytes and IS from plasma was performed using liquid-liquid extraction with ethyl acetate. The chromatographic separation of these prepared samples was achieved on Xterra MS C8 column (4.6×50mm,5μm) using gradient elution with a mobile phase of ammonium formate buffer (pH 3...
June 20, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28644610/mzmine-2-data-preprocessing-to-enhance-molecular-networking-reliability
#2
Florent Olivon, Gwendal Grelier, Fanny Roussi, Marc Litaudon, David Touboul
Molecular networking is becoming more and more popular into the metabolomic community to organize tandem mass spectrometry (MS2) data. Even though this approach allows the treatment and comparison of large data sets, several drawbacks related to the MS-Cluster tool routinely used on the Global Natural Product Social Molecular Networking platform (GNPS) limit its potential. MS-Cluster cannot distinguish between chromatography well-resolved isomers as retention times are not taken into account. Annotation with predicted chemical formulas is also not implemented and semi-quantification is only based on the number of MS2 scans...
June 23, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28644493/photoelectrochemical-devices-for-solar-water-splitting-materials-and-challenges
#3
Chaoran Jiang, Savio J A Moniz, Aiqin Wang, Tao Zhang, Junwang Tang
It is widely accepted within the community that to achieve a sustainable society with an energy mix primarily based on solar energy we need an efficient strategy to convert and store sunlight into chemical fuels. A photoelectrochemical (PEC) device would therefore play a key role in offering the possibility of carbon-neutral solar fuel production through artificial photosynthesis. The past five years have seen a surge in the development of promising semiconductor materials. In addition, low-cost earth-abundant co-catalysts are ubiquitous in their employment in water splitting cells due to the sluggish kinetics of the oxygen evolution reaction (OER)...
June 23, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28644114/midostaurin-plus-chemotherapy-for-acute-myeloid-leukemia-with-a-flt3-mutation
#4
Richard M Stone, Sumithra J Mandrekar, Ben L Sanford, Kristina Laumann, Susan Geyer, Clara D Bloomfield, Christian Thiede, Thomas W Prior, Konstanze Döhner, Guido Marcucci, Francesco Lo-Coco, Rebecca B Klisovic, Andrew Wei, Jorge Sierra, Miguel A Sanz, Joseph M Brandwein, Theo de Witte, Dietger Niederwieser, Frederick R Appelbaum, Bruno C Medeiros, Martin S Tallman, Jürgen Krauter, Richard F Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Richard A Larson, Hartmut Döhner
Background Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population. Methods We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo...
June 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28644085/pharmacokinetics-of-a-sustained-release-formulation-of-buprenorphine-after-intramuscular-and-subcutaneous-administration-to-american-kestrels-falco-sparverius
#5
David Sanchez-Migallon Guzman, Heather K Knych, Glenn H Olsen, Joanne R Paul-Murphy
Previous studies have validated the clinical use of opioids with μ-receptor affinities for pain management in raptors. Buprenorphine appears to have a longer duration of action and minimal adverse effects when compared to other opioids in American kestrels ( Falco sparverius ). To determine the pharmacokinetics of a sustained release formulation of buprenorphine in kestrels, we administered a commercially available product (Buprenorphine SR-LAB; Wildlife Pharmaceuticals, Windsor, CO, USA) intramuscularly and subcutaneously to adult kestrels in a partial-crossover experimental design study...
June 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/28644052/a-little-dab-will-do-ya-in-a-case-report-of-neuro-and-cardiotoxicity-following-use-of-cannabis-concentrates
#6
Shannon S Rickner, Dazhe Cao, Kurt Kleinschmidt, Steven Fleming
CONTEXT: The use of marijuana and cannabis concentrates is increasing, especially following decriminalization in several states. Psychosis and cardiotoxicity have been reported following cannabis use; however, myocardial injury from "dabbing" has not yet been reported. We report a case of hyperthermia, tachycardia, hypertension, severe agitation, neuro-, and cardiotoxicity following the use of "dabs" where there is concomitant confirmatory biological and sample testing. CASE DETAILS: A 17-year-old athletic man developed agitation requiring sedation and intubation for safety, with peak systolic blood pressures in the 190s and hyperthermia (to 102 °F)...
June 23, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28644029/a-tandem-oxidative-annulation-strategy-for-the-synthesis-of-tetracyclic-3-spirooxindole-benzofuranones
#7
Chunxia Zhang, Min Liu, Mingruo Ding, Hao Xie, Fengzhi Zhang
A simple and efficient method was developed for the construction of the medicinally important tetracyclic 3-spirooxindole benzofuranones. In this highly atom- and step-economical one-pot protocol, one quaternary carbon center, two new cycles, and four new bonds (C-C/C-O/C-N) were formed under simple ligand-free copper-catalyzed conditions through a novel tandem oxidative annulation strategy.
June 23, 2017: Organic Letters
https://www.readbyqxmd.com/read/28643853/qualitative-analysis-of-polyphenols-in-macroporous-resin-pretreated-pomegranate-husk-extract-by-hplc-qtof-ms
#8
Rahima Abdulla, Sanawar Mansur, Haizhong Lai, Ablikim Ubul, Guangying Sun, Guozheng Huang, Haji Akber Aisa
INTRODUCTION: Pomegranate (Punica granatum L.) husk is a traditional herbal medicine abundant in phenolic compounds and plays some roles in the treatment of oxidative stress, bacterial and viral infection, diabetes mellitus, and acute and chronic inflammation. OBJECTIVE: Identification and determination of polyphenols in macroporous resin pretreated pomegranate husk extract by high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS)...
June 23, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28643461/single-enzyme-biofuel-cells
#9
Chao Ji, Jingwei Hou, Kai Wang, Yun Hau Ng, Vicki Chen
Here, we firstly demonstrate that the intramolecular electron transfer within signle enzyme molecule is an important alternative pathway which can be harnessed to generate electricity. By decoupling the redox reactions within a single type of enzyme (e.g., Trametes versicolor laccase), we harvested electricity efficiently from unconventional fuels including recalcitrant pollutants (e.g. bisphenol-A and hydroquinon) in a single-laccase biofuel cell. The intramolecular electron-harnessing concept was further demonstrated with other enzymes, including power generation during CO2 bioconversion to formate catalyzed by formate dehydrogenase from Candida boidinii...
June 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28643275/open-label-single-sequence-crossover-study-evaluating-pharmacokinetics-efficacy-and-safety-of-once-daily-dosing-of-nitisinone-in-patients-with-hereditary-tyrosinemia-type-1
#10
Nathalie Guffon, Anders Bröijersén, Ingrid Palmgren, Mattias Rudebeck, Birgitta Olsson
BACKGROUND: Although nitisinone is successfully used to treat hereditary tyrosinemia type 1 (HT-1) with the recommended twice-daily dosing, data describing a long half-life motivate less frequent dosing. Therefore, in agreement with the Pharmacovigilance Risk Assessment Committee at the European Medicines Agency, this study was performed to investigate the switch to once-daily dosing. METHODS: This open-label, non-randomized, single-sequence crossover study evaluated the pharmacokinetics, efficacy, and safety of once-daily compared to twice-daily dosing of nitisinone in patients with HT-1 (NCT02323529)...
June 23, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28642739/genetic-variability-of-koi-herpesvirus-in-vitro-a-natural-event
#11
Sandro Klafack, Qing Wang, Weiwei Zeng, Yingying Wang, Yingying Li, Shucheng Zheng, Jolanta Kempter, Pei-Yu Lee, Marek Matras, Sven M Bergmann
Worldwide koi herpesvirus (KHV) causes high mortalities in Cyprinus carpio L. aquaculture. So far, it is unknown how the different variants of KHV have developed and how they spread in the fish, but also in the environmental water bodies. Therefore, a phylogenetic method based on variable number of tandem repeats (VNTR) was improved to gain deeper insights into the phylogeny of KHV and its possible worldwide distribution. Moreover, a VNTR-3 qPCR was designed which allows fast virus typing. This study presents a useful method for molecular tracing of diverse KHV types, variants, and lineages...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28642677/a-novel-workflow-combining-plaque-imaging-plaque-and-plasma-proteomics-identifies-biomarkers-of-human-coronary-atherosclerotic-plaque-disruption
#12
Regent Lee, Roman Fischer, Philip D Charles, David Adlam, Alessandro Valli, Katalin Di Gleria, Rajesh K Kharbanda, Robin P Choudhury, Charalambos Antoniades, Benedikt M Kessler, Keith M Channon
BACKGROUND: Atherosclerotic plaque rupture is the culprit event which underpins most acute vascular syndromes such as acute myocardial infarction. Novel biomarkers of plaque rupture could improve biological understanding and clinical management of patients presenting with possible acute vascular syndromes but such biomarker(s) remain elusive. Investigation of biomarkers in the context of de novo plaque rupture in humans is confounded by the inability to attribute the plaque rupture as the source of biomarker release, as plaque ruptures are typically associated with prompt down-stream events of myocardial necrosis and systemic inflammation...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28642470/quantitative-proteomics-analysis-reveals-novel-targets-of-mir-21-in-zebrafish-embryos
#13
Ying Wu, Qi-Yong Lou, Feng Ge, Qian Xiong
MicroRNAs (miRNAs) are noncoding RNAs which control gene expression by the suppression of translation or the degradation of mRNAs. Dre-miR-21 (miR-21) has been reported to impact cardiac valvulogenesis in zebrafish embryos. However, the target genes of miR-21 are still largely unknown. Here a tandem isobaric mass tag (TMT)-based quantitative proteomic strategy was employed to identify the global profile of miR-21-regulated proteins. A total of 251 proteins were dysregulated after miR-21 knockdown, suggesting that they may be regulated by miR-21...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641977/a-novel-fluorescent-probe-reveals-starvation-controls-the-commitment-of-amyloid-precursor-protein-to-the-lysosome
#14
Leanne K Hein, Pirjo M Apaja, Kathryn Hattersley, Randall H Grose, Jianling Xie, Christopher G Proud, Timothy J Sargeant
Alzheimer's disease is the most important cause of dementia but there is no therapy that has been demonstrated to stop or slow disease progression. Amyloid precursor protein (APP) is the source of amyloid-β (Aβ), which aggregates in Alzheimer's disease to form toxic oligomeric species. The endo-lysosomal system can clear APP and Aβ from the cell if these molecular species are trafficked through to the lysosome. Currently, there are no easy methods available for the analysis of lysosomal APP trafficking. We therefore generated a fusion protein (tandem-fluorescent, or tf-APP) that allows detection of changes in APP trafficking using accessible techniques such as flow cytometry...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641892/fighting-fake-medicines-first-quality-evaluation-of-cardiac-drugs-in-africa
#15
Marie Antignac, Bara Ibrahima Diop, Diane Macquart de Terline, Melisande Bernard, Bernard Do, Stéphane Méo Ikama, Roland N'Guetta, Dadhi M Balde, Yessoufou Tchabi, Abdallahi Sidi Aly, Ibrahim Ali Toure, Patrick Zabsonre, Jean Marie F Damorou, Jean Laurent Takombe, Christine Fernandez, Muriel Tafflet, Jean Philippe Empana, Pierre François Plouin, Kumar Narayanan, Eloi Marijon, Xavier Jouven
BACKGROUND: The growing menace of poor quality and falsified drugs constitutes a major hazard, compromising healthcare and patient outcomes. Efforts to assess drug standards worldwide have almost exclusively focused on anti-microbial drugs; with no study to date on cardiovascular drugs. Our study aims to assess quality of seven routinely used cardiovascular medications (anticoagulants, antihypertensives and statins) in ten Sub-Saharan African countries. METHODS: Drugs were prospectively collected using standardized methods between 2012 and 2014 from licensed (random pharmacies) and unlicensed (street-markets) places of sale in Africa...
June 19, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28641870/antibiotic-activity-and-concentrations-in-clinical-samples-from-patients-with-chronic-bacterial-prostatitis
#16
V Heras-Cañas, B Gutiérrez-Soto, H Almonte-Fernández, A Lara-Oya, J M Navarro-Marí, A Garrido-Frenich, F Vázquez-Alonso, J Gutiérrez-Fernández
OBJECTIVES: Chronic bacterial prostatitis (CBP) is the most common urological disease in patients younger than 50 years, whose long-standing symptoms could be related to an inappropriate therapeutic regimen. The objective was to analyse the sensitivity of microorganisms isolated from patients with CBP and measure the weekly antibiotic concentrations in serum, semen and urine. MATERIAL AND METHODS: For the antibiotic sensitivity study, 60 clinical isolates were included between January 2013 and December 2014 from semen samples from patients with microbiologically confirmed CBP...
June 19, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/28641534/interest-of-single-hair-analysis-to-document-drug-exposure-literature-review-and-a-case-report-involving-zuclopenthixol
#17
Nathalie Allibe, Pascal Kintz, Amandine Faure, François Paysant, Anne-Pascale Michard-Lenoir, Françoise Stanke-Labesque, Virginie Scolan, Hélène Eysseric-Guerin
The analysis of hair to detect drugs and drugs of abuse is performed in various contexts, including child protection cases, abstinence control programs, and workplace drug testing. This alternative matrix offers several advantages, such as a large detection window (months) and non-invasive collection. Segmental analysis of multiple hair strands for drugs and metabolites has been widely reported in the literature over the past three decades, whereas a review of the literature showed that there are only 26 articles that report the analysis of a single hair...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641015/a-regioselective-approach-to-trisubstituted-pyrazoles-via-palladium-catalyzed-oxidative-sonogashira-carbonylation-of-arylhydrazines
#18
Yongliang Tu, Zhenming Zhang, Tao Wang, Jiamei Ke, Junfeng Zhao
A palladium-catalyzed oxidative carbonylation of arylhydrazines and alkynes with balloon pressure CO/O2 to afford trisubstituted pyrazoles in a one-pot manner has been developed. The formation of trisubstituted pyrazoles involves a sequential C-N bond cleavage, carbonylation, Sonogashira coupling, Michael addition, and intramolecular condensation cyclization tandem process. An unprecedented oxidative Sonogashira-carbonylation reaction of arylhydrazine plays a key role for such a facile approach to pyrazoles...
June 22, 2017: Organic Letters
https://www.readbyqxmd.com/read/28640361/global-and-targeted-serum-metabolic-profiling-of-colorectal-cancer-progression
#19
Yin Long, Beatriz Sanchez-Espiridion, Moubin Lin, Lindsey White, Lopa Mishra, Gottumakkala S Raju, Scott Kopetz, Cathy Eng, Michelle A T Hildebrandt, David W Chang, Yuanqing Ye, Dong Liang, Xifeng Wu
BACKGROUND: Patients with colorectal adenoma polyps (PLPs) are at higher risk for developing colorectal cancer (CRC). However, the development of improved and robust biomarkers to enable the screening, surveillance, and early detection of PLPs and CRC continues to be a challenge. The aim of this study was to identify biomarkers of progression to CRC through metabolomic profiling of human serum samples with a multistage approach. METHODS: Metabolomic profiling was conducted with the Metabolon platform for 30 CRC patients, 30 PLP patients, and 30 control subjects, and this was followed by the targeted validation of the top metabolites in an additional set of 50 CRC patients, 50 PLP patients, and 50 controls with liquid chromatography-tandem mass spectrometry...
June 22, 2017: Cancer
https://www.readbyqxmd.com/read/28640062/an-atmospheric-pressure-ionization-ms-ms-assay-using-online-extraction-for-the-analysis-of-11-cannabinoids-and-metabolites-in-human-plasma-and-urine
#20
Jelena Klawitter, Cristina Sempio, Sophie Mörlein, Erik De Bloois, Jacek Klepacki, Thomas Henthorn, Maureen A Leehey, Edward J Hoffenberg, Kelly Knupp, George S Wang, Christian Hopfer, Greg Kinney, Russell Bowler, Nicholas Foreman, Jeffrey Galinkin, Uwe Christians, Jost Klawitter
BACKGROUND: Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmaco- and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids. METHODS: To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11OH-THC), 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol (CBN), cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma...
June 19, 2017: Therapeutic Drug Monitoring
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