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https://www.readbyqxmd.com/read/28922856/building-up-absence-seizures-in-the-somatosensory-cortex-from-network-to-cellular-epileptogenic-processes
#1
Guillaume Jarre, Tristan Altwegg-Boussac, Mark S Williams, Florian Studer, Mathilde Chipaux, Olivier David, Stéphane Charpier, Antoine Depaulis, Séverine Mahon, Isabelle Guillemain
The epileptogenic processes leading to recurrent seizures in Genetic Epilepsies are largely unknown. Using the Genetic Absence Epilepsy Rat from Strasbourg, we investigated in vivo the network and single neuron mechanisms responsible for the early emergence of epileptic activity. Local field potential recordings in the primary somatosensory cortex (SoCx), from the second post-natal week to adulthood, showed that immature cortical discharges progressively evolved into typical spike-and-wave discharges following a 3-step maturation process...
September 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28922838/comparative-genomics-of-a-drug-resistant-pseudomonas-aeruginosa-panel-and-the-challenges-of-antimicrobial-resistance-prediction-from-genomes
#2
J Jeukens, I Kukavica-Ibrulj, J G Emond-Rheault, L Freschi, R C Levesque
Antimicrobial resistance (AMR) is now recognized as a global threat to human health. The accessibility of microbial whole-genome sequencing offers an invaluable opportunity for resistance surveillance via the resistome, i.e. the genes and mutations underlying AMR. Unfortunately, AMR prediction from genomic data remains extremely challenging, especially for species with a large pan-genome. One such organism, for which multidrug-resistant (MDR) isolates are frequently encountered in the clinic, is Pseudomonas aeruginosa...
October 2, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28922811/a-programme-to-create-short-course-chemotherapy-for-pulmonary-mycobacterium-avium-disease-based-on-pharmacokinetics-pharmacodynamics-and-mathematical-forecasting
#3
Devyani Deshpande, Shashikant Srivastava, Tawanda Gumbo
Objectives: Pulmonary Mycobacterium avium complex (MAC) prevalence is on the rise worldwide. The average therapy duration is 1.5 years, which is associated with poor cure rates. Our objective was to develop a programme to design a combination therapy regimen for pulmonary MAC to be administered for 6 months or less with efficacy in > 90% of patients. Methods: We performed a literature search for the following MeSH headings 'Mycobacterium avium' AND 'pharmacokinetics/pharmacodynamics' in PubMed up to 2016...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922809/a-novel-ceftazidime-avibactam-rifabutin-tedizolid-and-moxifloxacin-cartm-regimen-for-pulmonary-mycobacterium-avium-disease
#4
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922808/the-discovery-of-ceftazidime-avibactam-as-an-anti-mycobacterium-avium-agent
#5
Devyani Deshpande, Shashikant Srivastava, Moti L Chapagain, Pooi S Lee, Kayle N Cirrincione, Jotam G Pasipanodya, Tawanda Gumbo
Objectives: To determine if ceftaroline and ceftazidime combined with avibactam are efficacious against pulmonary Mycobacterium avium complex (MAC) disease. Methods: First, we performed a concentration-effect study of ceftaroline and ceftaroline/avibactam against extracellular MAC in test tubes. Given the difficulty of obtaining avibactam at the time of experimentation, we used a single concentration of commercial ceftazidime/avibactam, and two sets of non-treated controls, one with ceftazidime/avibactam and the other without...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922731/shikonin-suppresses-pulmonary-fibroblasts-proliferation-and-activation-by-regulating-akt-and-p38-mapk-signaling-pathways
#6
Yunjuan Nie, Yaoyao Yang, Jian Zhang, Guowei Cai, Yanhua Chang, Gaoshang Chai, Chongyong Guo
Fibroblast is believed to be the primary effector in idiopathic pulmonary fibrosis (IPF), a progressive lung disorder characterized by aberrant tissue remodeling and the formation of fibroblastic foci. Due to the complicated etiology and mechanism, there are few effective drugs for this fatal disease. Shikonin (SHI), which is the major ingredient isolated from the plant Lithospermum Erythrorhizon, has long been used as traditional medicine for many diseases including inflammation and cancer. The roles of SHI in attenuating skin scar and renal fibrosis by reducing TGFβ1-stimulated fibroblast activation are also reported...
September 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922704/direct-acting-antivirals-for-chronic-hepatitis-c
#7
REVIEW
Janus C Jakobsen, Emil Eik Nielsen, Joshua Feinberg, Kiran Kumar Katakam, Kristina Fobian, Goran Hauser, Goran Poropat, Snezana Djurisic, Karl Heinz Weiss, Milica Bjelakovic, Goran Bjelakovic, Sarah Louise Klingenberg, Jian Ping Liu, Dimitrinka Nikolova, Ronald L Koretz, Christian Gluud
BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir, are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response). Sustained virological response (SVR) is used by investigators and regulatory agencies as a surrogate outcome for morbidity and mortality, based solely on observational evidence...
September 18, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28922692/phosphodiesterase-4-inhibitors-for-chronic-obstructive-pulmonary-disease
#8
REVIEW
Jimmy Chong, Bonnie Leung, Phillippa Poole
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This is an update of a Cochrane review first published in 2011 and updated in 2013...
September 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28922657/methods-employed-in-cytofluorometric-assessment-of-eryptosis-the-suicidal-erythrocyte-death
#9
Mohamed Jemaà, Myriam Fezai, Rosi Bissinger, Florian Lang
Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28922652/a-pilot-study-of-loss-aversion-for-drug-and-non-drug-commodities-in-cocaine-users
#10
Justin C Strickland, Joshua S Beckmann, Craig R Rush, William W Stoops
BACKGROUND: Numerous studies in behavioral economics have demonstrated that individuals are more sensitive to the prospect of a loss than a gain (i.e., loss aversion). Although loss aversion has been well described in "healthy" populations, little research exists in individuals with substance use disorders. This gap is notable considering the prominent role that choice and decision-making play in drug use. The purpose of this pilot study was to evaluate loss aversion in active cocaine users...
September 12, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28922644/temperature-dependent-polymorphism-of-pyrazinamide-an-in-situ-raman-and-dft-study
#11
Poornima Sharma, Rajib Nandi, Debraj Gangopadhyay, Anurag Singh, Ranjan K Singh
The α and γ polymorphs of drug pyrazinamide have been detected with the help of temperature dependent Raman spectroscopic technique. Pyrazinamide is a very useful drug used for the treatment of tuberculosis (TB) and plays a significant role in destroying the dormant tubercle bacilli which are not destroyed by other common TB drugs. Temperature dependent Raman spectra suggest polymorphic phase change from α→γ form of pyrazinamide between 145 and 146°C. In situ Raman spectra of pyrazinamide between 145 and 146°C show the conversion of α→γ form by the shift in CO stretching vibration accompanied by several other changes...
September 13, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28922640/a-novel-spectroscopic-analysis-to-detect-photochemical-reaction-of-the-bronchodilator-doxofylline-and-its-estimation-in-pharmaceutical-formulation
#12
P Sasi Rekha, S Gunasekaran
Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy and safety of the formulated products during manufacture, storage and use. In this investigation, a novel spectroscopic approach has been adopted by employing the FTIR-ATR and UV/Visible techniques to detect the photochemical reactions of the drug Doxofylline, chemically designated as 7-(1, 3 dioxolane-2-yl methyl) theophylline, in its raw (pure) form...
September 11, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28922634/functionalisation-of-ti6al4v-and-hydroxyapatite-surfaces-with-combined-peptides-based-on-kklpda-and-eeeeeeee-peptides
#13
Gabriela Melo Rodriguez, James Bowen, David Grossin, Besim Ben-Nissan, Artemis Stamboulis
Surface modifications are usually performed on titanium alloys to improve osteo-integration and surface bioactivity. Modifications such as alkaline and acid etching, or coating with bioactive materials such as hydroxyapatite, have previously been demonstrated. The aim of this work is to develop a peptide with combined titanium oxide and hydroxyapatite binders in order to achieve a biomimetic hydroxyapatite coating on titanium surfaces. The technology would also be applicable for the functionalisation of titanium and hydroxyapatite surfaces for selective protein adsorption, conjugation of antimicrobial peptides, and adsorption of specialised drugs for drug delivery...
September 9, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28922619/identification-of-angiogenesis-inhibitors-using-a-co-culture-cell-model-in-a-high-content-and-high-throughput-screening-platform
#14
Shuaizhang Li, Chia-Wen Hsu, Srilatha Sakamuru, Chaozhong Zou, Ruili Huang, Menghang Xia
Angiogenesis is an important hallmark of cancer, contributing to tumor formation and metastasis. In vitro angiogenesis models for analyzing tube formation serve as useful tools to study these processes. However, current in vitro co-culture models using primary cells have limitations in usefulness and consistency. Therefore, in the present study, an in vitro co-culture assay system was optimized in a 1536-well format for high-throughput screening using human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cells and aortic endothelial cells...
September 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28922604/a-comparative-study-on-the-performance-of-inert-and-functionalized-spheres-coated-with-solid-dispersions-made-of-two-structurally-related-antifungal-drugs
#15
Naila A Mugheirbi, Peter O'Connell, Dolores R Serrano, Anne Marie Healy, Lynne S Taylor, Lidia Tajber
Fluid bed coating offers potential advantages as a formulation platform for amorphous solid dispersions (ASDs) of poorly soluble drugs, being a one-step manufacturing process which could reduce the risk of phase separation associated with multiple step manufacturing approaches. However, the impact of the physicochemical nature of carrier spheres on the properties and drug release from the ASDs has not been studied in detail. In this work, tartaric acid (TAP) and microcrystalline cellulose (CEL) spheres were chosen as examples of functional and inert beads, respectively...
September 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28922540/ape1-ref-1-knockdown-in-pancreatic-ductal-adenocarcinoma-characterizing-gene-expression-changes-and-identifying-novel-pathways-using-single-cell-rna-sequencing
#16
Fenil Shah, Emery Goossens, Nadia M Atallah, Michelle Grimard, Mark R Kelley, Melissa L Fishel
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1 or APE1) is a multifunctional protein that regulates numerous transcription factors associated with cancer-related pathways. Because APE1 is essential for cell viability, generation of APE1 knockout cell lines and determining a comprehensive list of genes regulated by APE1 has not been possible. To circumvent this challenge, we utilized single-cell RNA Sequencing to identify differentially expressed genes in relation to APE1 protein levels within the cell...
September 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28922506/organoruthenium-complexes-with-c-n-ligands-are-highly-potent-cytotoxic-agents-that-act-by-a-new-mechanism-of-action
#17
Vojtech Novohradsky, Jyoti Yellol, Olga Stuchlikova, María Dolores Santana, Hana Kostrhunova, Gorakh Yellol, Jana Kasparkova, Delia Bautista, Jose Ruiz, Viktor Brabec
Our study demonstrates that four novel substitutionally inert C,N-cyclometalated Ru(II) complexes of the type [Ru(C^N)(N^N)2][PF6] containing a handle for functionalization in the C^N ligand are very potent cytotoxic agents against several different human cancer cell lines and are up to 400-fold more potent than clinically used cisplatin. In addition, the investigated ruthenium complexes are less cytotoxic in noncancerous cells, and exhibit higher selectivity for cancer cells than conventional platinum anticancer drugs...
September 18, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28922497/mutual-independence-of-alkaline-and-calcium-mediated-signalling-in-aspergillus-fumigatus-refutes-the-existence-of-a-conserved-druggable-signalling-nexus
#18
Omar Loss, Margherita Bertuzzi, Yu Yan, Natalie Fedorova, Bethany L McCann, Darius Armstrong-James, Eduardo A Espeso, Nick D Read, William C Nierman, Elaine M Bignell
Functional coupling of calcium- and alkaline responsive signalling occurs in multiple fungi to afford efficient cation homeostasis. Host microenvironments exert alkaline stress and potentially toxic concentrations of Ca(2+) , such that highly conserved regulators of both calcium- (Crz) and pH- (PacC/Rim) responsive signalling are crucial for fungal pathogenicity. Drugs targeting calcineurin are potent antifungal agents but also perturb human immunity thereby negating their use as anti-infectives, abrogation of alkaline signalling has therefore been postulated as an adjunctive antifungal strategy...
September 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28922469/one-pot-synthesis-of-gdp-mannose-by-a-multi-enzyme-cascade-for-enzymatic-assembly-of-lipid-linked-oligosaccharides
#19
Thomas F T Rexer, Anna Schildbach, Jan Klapproth, Angelika Schierhorn, Reza Mahour, Markus Pietzsch, Erdmann Rapp, Udo Reichl
Glycosylation of proteins is a key function of the biosynthetic-secretory pathway in the endoplasmic reticulum (ER) and Golgi apparatus. Glycosylated proteins play a crucial role in cell trafficking and signaling, cell-cell adhesion, blood-group antigenicity, and immune response. In addition, the glycosylation of proteins is an important parameter in the optimization of many glycoprotein-based drugs such as monoclonal antibodies. In vitro glycoengineering of proteins requires glycosyltransferases as well as expensive nucleotide sugars...
September 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28922449/needle-syringe-programmes-and-opioid-substitution-therapy-for-preventing-hepatitis-c-transmission-in-people-who-inject-drugs
#20
REVIEW
Lucy Platt, Silvia Minozzi, Jennifer Reed, Peter Vickerman, Holly Hagan, Clare French, Ashly Jordan, Louisa Degenhardt, Vivian Hope, Sharon Hutchinson, Lisa Maher, Norah Palmateer, Avril Taylor, Julie Bruneau, Matthew Hickman
BACKGROUND: Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugsNeedle syringe programmes (NSP) and opioid substitution therapy (OST) are the primary interventions to reduce hepatitis C (HCV) transmission in people who inject drugs. There is good evidence for the effectiveness of NSP and OST in reducing injecting risk behaviour and increasing evidence for the effectiveness of OST and NSP in reducing HIV acquisition risk, but the evidence on the effectiveness of NSP and OST for preventing HCV acquisition is weak...
September 18, 2017: Cochrane Database of Systematic Reviews
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