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https://www.readbyqxmd.com/read/29212448/from-genomes-to-genotypes-molecular-epidemiological-analysis-of-chlamydia-gallinacea-reveals-a-high-level-of-genetic-diversity-for-this-newly-emerging-chlamydial-pathogen
#1
Weina Guo, Martina Jelocnik, Jing Li, Konrad Sachse, Adam Polkinghorne, Yvonne Pannekoek, Bernhard Kaltenboeck, Jiansen Gong, Jinfeng You, Chengming Wang
BACKGROUND: Chlamydia (C.) gallinacea is a recently identified bacterium that mainly infects domestic chickens. Demonstration of C. gallinacea in human atypical pneumonia suggests its zoonotic potential. Its prevalence in chickens exceeds that of C. psittaci, but genetic and genomic research on C. gallinacea is still at the beginning. In this study, we conducted whole-genome sequencing of C. gallinacea strain JX-1 isolated from an asymptomatic chicken, and comparative genomic analysis between C...
December 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29211817/qtwist-analysis-of-the-recourse-trial-of-trifluridine-tipiracil-in-metastatic-colorectal-cancer
#2
Josep Tabernero, Eric Van Cutsem, Atsushi Ohtsu, Nadia Amellal, Stéphanie Cadour, Ronan Fougeray, Benjamin Haffemayer, Robert J Mayer
Purpose: A Quality-adjusted Time WIthout Symptoms of disease or Toxicity (QTWiST) analysis was carried out to assess quality-adjusted survival time in the RECOURSE trial of trifluridine/tipiracil versus placebo in pretreated metastatic colorectal cancer (mCRC). Methods: Duration of overall survival in the RECOURSE trial (n=798 patients) was partitioned into three discrete health states: toxicity (TOX), time without symptoms or toxicity (TWIST) and relapse (REL)...
2017: ESMO Open
https://www.readbyqxmd.com/read/29194347/in-vivo-and-in-vitro-activities-and-adme-tox-profile-of-a-quinolizidine-modified-4-aminoquinoline-a-potent-anti-p-falciparum-and-anti-p-vivax-blood-stage-antimalarial
#3
Nicoletta Basilico, Silvia Parapini, Anna Sparatore, Sergio Romeo, Paola Misiano, Livia Vivas, Vanessa Yardley, Simon L Croft, Annette Habluetzel, Leonardo Lucantoni, Laurent Renia, Bruce Russell, Rossarin Suwanarusk, Francois Nosten, Giulio Dondio, Chiara Bigogno, Daniela Jabes, Donatella Taramelli
Natural products are a prolific source for the identification of new biologically active compounds. In the present work, we studied the in vitro and in vivo antimalarial efficacy and ADME-Tox profile of a molecular hybrid (AM1) between 4-aminoquinoline and a quinolizidine moiety derived from lupinine (Lupinus luteus). The aim was to find a compound endowed with the target product profile-1 (TCP-1: molecules that clear asexual blood-stage parasitaemia), proposed by the Medicine for Malaria Venture to accomplish the goal of malaria elimination/eradication...
December 1, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29194289/lack-of-detection-of-new-amphetamine-like-drugs-using-conventional-urinary-immunoassays
#4
A Begeman, E J F Franssen
BACKGROUND: The number of reports of serious adverse effects and intoxication after the use of the new drug 4-fluoroamphetamine (4-FA) increases. At the Emergency Department of the OLVG-Oost Hospital in Amsterdam an on-site drug test, the Triage® TOX Drug Screen, is available to assist in a rapid diagnosis. In less urgent cases, an EMIT® II Plus immunoassay is used to determine semi-quantitatively the presence of drugs of abuse. The antibodies in these immunoassays are designed to detect classic drugs of abuse and its urinary metabolites...
November 29, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29193815/introduction-to-special-section-on-using-pools-to-generate-good-laboratory-practice-tox-or-other-non-clinical-material-to-accelerate-development-timelines
#5
Christine DeMaria, Trent Munro
No abstract text is available yet for this article.
November 28, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/29175927/anti-tox-range-for-companion-animals
#6
(no author information available yet)
No abstract text is available yet for this article.
November 25, 2017: Veterinary Record
https://www.readbyqxmd.com/read/29171771/icp-ms-determination-of-serum-aluminum-in-monkeys-subcutaneously-administered-an-alhydrogel-formulated-drug-candidate
#7
Wenkui Li, Jiawei Gong, Chuan Wang, Zhongping John Lin, Jimmy Flarakos
AIM: To develop and validate an inductively coupled plasma-mass spectrometry method for quantitative bioanalysis of aluminum (Al) in monkey serum in support of a GLP TOX study with alhydrogel-formulated drug candidate. METHODS & RESULTS: The method was linear over a dynamic range of 10-1000 ng/ml using a 50-μl sample volume. The intra-/inter-run precision (%CV) of the quality control sample results were ≤7.9% (CV) and the accuracy (%bias) within ±11.0% across all quality control concentrations evaluated...
November 24, 2017: Bioanalysis
https://www.readbyqxmd.com/read/29132312/genomic-analysis-of-endemic-clones-of-toxigenic-and-non-toxigenic-corynebacterium-diphtheriae-in-belarus-during-and-after-the-major-epidemic-in-1990s
#8
Steffen Grosse-Kock, Valentina Kolodkina, Edward C Schwalbe, Jochen Blom, Andreas Burkovski, Paul A Hoskisson, Sylvain Brisse, Darren Smith, Iain C Sutcliffe, Leonid Titov, Vartul Sangal
BACKGROUND: Diphtheria remains a major public health concern with multiple recent outbreaks around the world. Moreover, invasive non-toxigenic strains have emerged globally causing severe infections. A diphtheria epidemic in the former Soviet Union in the 1990s resulted in ~5000 deaths. In this study, we analysed the genome sequences of a collection of 93 C. diphtheriae strains collected during and after this outbreak (1996 - 2014) in a former Soviet State, Belarus to understand the evolutionary dynamics and virulence capacities of these strains...
November 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29128859/-vigilance-for-veterinary-medicinal-products-reports-of-adverse-reactions-in-the-year-2016
#9
C R Müntener, C Müntener, J Kupper, H Naegeli, B Gassner
A total of 253 reports of adverse reactions to veterinary medicinal products were received during the year 2016 representing a decrease of 13% compared to the previous year (292 reports). The majority of the reports described reactions affecting companion animals (178 dogs and 32 cats) as well as cattle (17 reports) and horses (10 reports). Most of the reactions reported were linked to the use of antiparasitics (145 reports), hormone products (26 reports) and antiinfectives (10 reports). 32 reports were generated from consultations with Tox Info Suisse in Zürich and involved mainly the excessive intake of flavoured tablets and, in some cases, the use of reconverted products (applied to another species than that authorized)...
November 2017: Schweizer Archiv Für Tierheilkunde
https://www.readbyqxmd.com/read/29108774/gender-based-behavioral-and-biochemical-effects-of-diphenyl-diselenide-in-drosophila-melanogaster
#10
Bruna Karoline Occai, Waseem Hassan, João Batista Teixeira da Rocha
In the present study we investigated the effects of Diphenyl Diselenide (DPDS) on behavioral and biochemical parameters in Drosophila melanogaster (DM). We also tried to explore the gender differences in response to DPDS treatment. One of the salient features of the present report is that, at the highest tested concentration (3.0 mmol/kg) the survival rate in females was significantly higher (65%) as compared with male subjects (27.5%). However in alive subjects, different results pattern was observed. The locomotor activity of females significantly decreased at all tested concentrations and no statistical difference was observed in males at 0...
November 3, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29096442/comparison-of-deep-learning-with-multiple-machine-learning-methods-and-metrics-using-diverse-drug-discovery-datasets
#11
Alexandru Korotcov, Valery Tkachenko, Daniel P Russo, Sean Ekins
Machine learning methods have been applied to many datasets in pharmaceutical research for several decades. The relative ease and availability of fingerprint type molecular descriptors paired with Bayesian methods resulted in the widespread use of this approach for a diverse array of endpoints relevant to drug discovery. Deep learning is the latest machine learning algorithm attracting attention for many of pharmaceutical applications from docking to virtual screening. Deep learning is based on an artificial neural network with multiple hidden layers and has found considerable traction for many artificial intelligence applications...
November 2, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29076424/physicochemical-characterization-of-mitragyna-speciosa-alkaloid-extract-and-mitragynine-using-in-vitro-high-throughput-assays
#12
Wai Mun Kong, Zamri Chik, Zahurin Mohamed, Mohammed A Alshawsh
Mitragynine, a major active alkaloid of Mitragyna speciosa, acts as an agonist on μ-opioid receptors, producing effects similar to morphine and other opioids. It has been traditionally utilized to alleviate opiate withdrawal symptoms. Besides consideration about potency and selectivity, a good drug must possess a suitable pharmacokinetic profile, with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) profile, in order to have a high chance of success in clinical trials. The purity of mitragynine in a Mitragyna speciosa alkaloid extract (MSAE) was determined using Ultra-Fast Liquid Chromatography (UFLC)...
October 26, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/29075239/insight-of-genus-corynebacterium-ascertaining-the-role-of-pathogenic-and-non-pathogenic-species
#13
REVIEW
Alberto Oliveira, Leticia C Oliveira, Flavia Aburjaile, Leandro Benevides, Sandeep Tiwari, Syed B Jamal, Arthur Silva, Henrique C P Figueiredo, Preetam Ghosh, Ricardo W Portela, Vasco A De Carvalho Azevedo, Alice R Wattam
This review gathers recent information about genomic and transcriptomic studies in the Corynebacterium genus, exploring, for example, prediction of pathogenicity islands and stress response in different pathogenic and non-pathogenic species. In addition, is described several phylogeny studies to Corynebacterium, exploring since the identification of species until biological speciation in one species belonging to the genus Corynebacterium. Important concepts associated with virulence highlighting the role of Pld protein and Tox gene...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29056366/natural-modulators-of-nonalcoholic-fatty-liver-disease-mode-of-action-analysis-and-in-silico-adme-tox-prediction
#14
Merilin Al Sharif, Petko Alov, Vessela Vitcheva, Antonia Diukendjieva, Mattia Mori, Bruno Botta, Ivanka Tsakovska, Ilza Pajeva
Nonalcoholic fatty liver disease (NAFLD) is considered to be the most common chronic liver disease. The discovery of natural product-based NAFLD modulators requires a more comprehensive study of their modes of action (MoAs). In this study we analysed available in the literature data for 26 naturally-derived compounds associated with experimental evidence for NAFLD alleviation and outlined potential biomolecular targets and a network of pharmacological MoAs for 12 compounds with the highest number of experimentally supported MoA key events, modulated by them...
December 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29045053/ensamble-based-adme-tox-profiling-and-virtual-screening-for-the-discovery-of-new-inhibitors-of-the-leishmania-mexicana-cysteine-protease-cpb2-8%C3%AE-cte
#15
Angela Scala, Antonio Rescifina, Nicola Micale, Anna Piperno, Tanja Schirmeister, Louis Maes, Giovanni Grassi
In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8ΔCTE, fused benzo[b]thiophenes and β,β'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate to excellent activity (12-90% inhibition of the target enzyme at 20 μM). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-topology...
October 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29039210/mailbox-tox-ingestion-of-a-pharmaceutical-product-stolen-from-a-mailbox
#16
Jacob A Kanter, Neeraj Chhabra, Michele Zell-Kanter
No abstract text is available yet for this article.
October 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28990518/click-reactions-in-chemistry-of-triterpenes-advances-towards-development-of-potential-therapeutics
#17
Jan Pokorný, Lucie Borková, Milan Urban
Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use...
October 9, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28988506/in-silico-adme-tox-modeling-progress-and-prospects
#18
REVIEW
Saeed Alqahtani
Although significant progress has been made in high-throughput screening of absorption, distribution, metabolism and excretion, and toxicity (ADME-Tox) properties in drug discovery and development, in silico ADME-Tox prediction continues to play an important role in facilitating the appropriate selection of candidate drugs by pharmaceutical companies prior to expensive clinical trials. Areas covered: This review provides an overview of the available in silico models that have been used to predict the ADME-Tox properties of compounds...
November 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28985315/cross-reactivity-of-pantoprazole-with-three-commercial-cannabinoids-immunoassays-in-urine
#19
Isabel Gomila, Bernardino Barceló, Antonio Rosell, Sonia Avella, Laura Sahuquillo, Macarena Dastis
Pantoprazole is a frequently prescribed proton pump inhibitor (PPI) commonly utilized in the management of gastrointestinal symptoms. Few substances have proved to cause a false-positive cannabinoid urine screen. However, a case of false-positive urine cannabinoid screen in a patient who received a pantoprazole dose has been recently published. The purpose of this study was to determine the potential cross-reactivity of pantoprazole in the cannabinoid immunoassays: Alere Triage® TOX Drug Screen, KIMS® Cannabinoids II and DRI® Cannabinoids Assay...
July 13, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28974511/tox-regulates-growth-dna-repair-and-genomic-instability-in-t-cell-acute-lymphoblastic-leukemia
#20
Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S Blackburn, Brian J Abraham, Yuka Namiki, Marc Mansour, Nouran S Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon de Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B Silverman, Ruslan I Sadreyev, John M Asara, Marjorie A Oettinger, Wilhelm Haas, A Thomas Look, Richard A Young, Raul Mostoslavsky, Graham Dellaire, David M Langenau
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection-associated high mobility group box protein (TOX) was uncovered as a collaborating oncogenic driver that accelerated T-ALL onset by expanding the initiating pool of transformed clones and elevating genomic instability. TOX is highly expressed in a majority of human T-ALL and is required for proliferation and continued xenograft growth in mice. Using a wide array of functional analyses, we uncovered that TOX binds directly to KU70/80 and suppresses recruitment of this complex to DNA breaks to inhibit nonhomologous end joining (NHEJ) repair...
November 2017: Cancer Discovery
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