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drug testing

Anil Prasad, Nagina Khudaynazar, Ramana V Tantravahi, Amanda M Gillum, Benjamin S Hoffman
Squamous cell carcinoma of the head and neck (HNSCC) is characterized by high morbidity and mortality. Treatment failure, drug resistance and chemoradiation toxicity have necessitated the development of alternative treatment strategies. Styryl benzyl sulfones, a family of novel small molecule inhibitors, are being evaluated as anti-neoplastic agents in multiple clinical trials. The activity of these compounds has been well characterized in several preclinical tumor studies, but their activity has yet to be fully examined in HNSCC...
October 15, 2016: Oncotarget
Yuan-Bo Wu, Li Zhang, Wen-Ting Li, Yi Yang, Jiang-Ming Zhao
BACKGROUND: Artesunate (ART) is an antimalarial drug with potential anti-inflammatory effect. This study aimed to explore the potential protective role of ART in hepatic encephalopathy (HE), involving its function against ammonia toxicity. METHODS: HE rats were induced by the administration of thioacetamide (TAA, 300mg/kg/day). Spatial learning ability was tested in both Morris water and eight-arm radial maze. Rat cerebellar granule neurons (CGNs) were prepared for ammonia treatment in vitro, in line with SH-SY5Y and C6 cells...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shufang Dong, Xin Zhou, Jiying Yang
BACKGROUND: Co-delivery of anticancer drugs and gene is promising to generate synergistic anticancer effects. Surface modification of nanocarriers with specific ligands could further assist in targeting and internalization of the nanocarriers into specific cell populations, such as cancers and disease organs. PURPOSE: The aim of the study reported here is to develop Cell-penetrating peptides (CPPs) modified lipid - PEI hybrid nanoparticles (LPNs) for effective co-delivery of docetaxel (DTX) and plasmid DNA (pDNA) for combination chemotherapy...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Urszula K Komarnicka, Radosław Starosta, Agnieszka Kyzioł, Michał Płotek, Małgorzata Puchalska, Małgorzata Jeżowska-Bojczuk
In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV-Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods...
September 30, 2016: Journal of Inorganic Biochemistry
Matthias Samwald, Hong Xu, Kathrin Blagec, Philip E Empey, Daniel C Malone, Seid Mussa Ahmed, Patrick Ryan, Sebastian Hofer, Richard D Boyce
Pre-emptive pharmacogenomic (PGx) testing of a panel of genes may be easier to implement and more cost-effective than reactive pharmacogenomic testing if a sufficient number of medications are covered by a single test and future medication exposure can be anticipated. We analysed the incidence of exposure of individual patients in the United States to multiple drugs for which pharmacogenomic guidelines are available (PGx drugs) within a selected four-year period (2009-2012) in order to identify and quantify the incidence of pharmacotherapy in a nation-wide patient population that could be impacted by pre-emptive PGx testing based on currently available clinical guidelines...
2016: PloS One
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
Mercedes Fernández-Moreno, Tamara Hermida-Gómez, M Esther Gallardo, Andrea Dalmao-Fernández, Ignacio Rego-Pérez, Rafael Garesse, Francisco J Blanco
INTRODUCTION: The generation of Rho-0 cells requires the use of an immortalization process, or tumor cell selection, followed by culture in the presence of ethidium bromide (EtBr), incurring the drawbacks its use entails. The purpose of this work was to generate Rho-0 cells using human mesenchymal stem cells (hMSCs) with reagents having the ability to remove mitochondrial DNA (mtDNA) more safely than by using EtBr. METHODOLOGY: Two immortalized hMSC lines (3a6 and KP) were used; 143B...
2016: PloS One
Sean Ekins, Alexander L Perryman, Carolina Horta Andrade
The Zika virus outbreak in the Americas has caused global concern. To help accelerate this fight against Zika, we launched the OpenZika project. OpenZika is an IBM World Community Grid Project that uses distributed computing on millions of computers and Android devices to run docking experiments, in order to dock tens of millions of drug-like compounds against crystal structures and homology models of Zika proteins (and other related flavivirus targets). This will enable the identification of new candidates that can then be tested in vitro, to advance the discovery and development of new antiviral drugs against the Zika virus...
October 2016: PLoS Neglected Tropical Diseases
Mojgan Aminnejad, Massimo Cogliati, Shuyao Duan, Michael Arabatzis, Kathrin Tintelnot, Elizabeth Castañeda, Marcia Lazéra, Aristea Velegraki, David Ellis, Tania C Sorrell, Wieland Meyer
Cryptococcus neoformans and C. gattii are pathogenic basidiomycetous yeasts and the commonest cause of fungal infection of the central nervous system. Cryptococci are typically haploid but several inter-species, inter-varietal and intra-varietal hybrids have been reported. It has a bipolar mating system with sexual reproduction occurring normally between two individuals with opposite mating types, α and a. This study set out to characterize hybrid isolates within the C. neoformans/C. gattii species complex: seven unisexual mating intra-varietal VNI/VNII (αAAα) and six novel inter-varietal VNII/VNIV (aADα)...
2016: PloS One
Anna B Cope, Catalina Ramirez, Robert F DeVellis, Robert Agans, Victor J Schoenbach, Adaora A Adimora
BACKGROUND: Concurrent sexual partnerships (partnerships that overlap in time) may contribute to higher rates of HIV transmission in African Americans. Attitudes toward a behavior constitute an important component of most models of health-related behavior and behavioral change. We have developed a scale, employing realistic vignettes that appear to reliably measure attitudes about concurrency in young African American adults. METHODS: Vignette-based items to assess attitudes about concurrency were developed following focus groups and cognitive testing of items adapted from existing scales assessing psychosocial constructs surrounding related sexual behaviors...
2016: PloS One
Lia Gvinjilia, Muazzam Nasrullah, David Sergeenko, Tengiz Tsertsvadze, George Kamkamidze, Maia Butsashvili, Amiran Gamkrelidze, Paata Imnadze, Valeri Kvaratskhelia, Nikoloz Chkhartishvili, Lali Sharvadze, Jan Drobeniuc, Liesl Hagan, John W Ward, Juliette Morgan, Francisco Averhoff
The country of Georgia has a high prevalence of hepatitis C virus (HCV) infection, associated with exposures to HCV in health care settings with inadequate infection control and unsafe injections among persons who inject drugs (1). In April 2015, in collaboration with CDC and other partners, Georgia embarked on a program to eliminate HCV infection, subsequently defined as achieving a 90% reduction in prevalence by 2020. The initial phase of the program focused on providing HCV treatment to infected persons with advanced liver disease and at highest risk for HCV-associated morbidity and mortality...
October 21, 2016: MMWR. Morbidity and Mortality Weekly Report
Lauren Brasile, Nicholas Henry, Bart Stubenitsky
BACKGROUND: We have previously reported on a novel organ-specific immunomodifying therapy that provides protection from early allograft rejection in the absence of systemic immunosuppressive drugs. This novel therapy is a nano-barrier membrane called ImmunoCloak, consisting of a matrix of laminin, proteoglycans, fibronectin and collagens. The membrane "immunocloaks" the luminal surfaces within the renal vasculature by covering the point of contact between donor vascular endothelial cells and the recipient's immune cells; without adversely affecting renal function...
October 19, 2016: Transplantation
Lawrence C Ku, Huali Wu, Rachel G Greenberg, Kevin D Hill, Daniel Gonzalez, Christoph P Hornik, Alysha Berezny, Jeffrey T Guptill, Wenlei Jiang, Nan Zheng, Michael Cohen-Wolkowiez, Chiara Melloni
BACKGROUND: Defining a drug's therapeutic index (TI) is important for patient safety and regulating the development of generic drugs. For many drugs, the TI is unknown. A systematic approach was developed to characterize the TI of a drug using therapeutic drug monitoring and electronic health record (EHR) data with pharmacokinetic (PK) modeling. This approach was first tested on phenytoin, which has a known TI, and then applied to lamotrigine, which lacks a defined TI. METHODS: Retrospective EHR data from patients in a tertiary hospital were used to develop phenytoin and lamotrigine population PK models and to identify adverse events (anemia, thrombocytopenia, and leukopenia) and efficacy outcomes (seizure-free)...
October 19, 2016: Therapeutic Drug Monitoring
Sivakumar Sanjeev, Deepti Zutshi, Navid Seraji-Bozorgzad, Aashit Shah
Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series and clinical trials. However, literature on their electroencephalography (EEG) effects is sparse. Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy (IGE) treated with cannabis. We blindly reviewed three long-term EEGs-a 24-hour study while only on antiepileptic drugs (AEDs), a 72-hour EEG with Cannabis indica smoked on days one and three in addition to AEDs and a 48-hour EEG with combination C...
October 18, 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Lesley K Rao, Alicia M Flaker, Christina C Friedel, Evan D Kharasch
BACKGROUND: At therapeutic concentrations, cytochrome P4502B6 (CYP2B6) is the major P450 isoform catalyzing hepatic ketamine N-demethylation to norketamine in vitro. The CYP2B6 gene is highly polymorphic. The most common variant allele, CYP2B6*6, is associated with diminished hepatic CYP2B6 expression and catalytic activity compared with wild-type CYP2B6*1/*1. CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro...
October 20, 2016: Anesthesiology
Grzegorz Fila, Anna Kawiak, Mariusz Grinholc
Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antimicrobials has increased rapidly over the past decade. Therefore, it is crucial to explore new therapeutic options, particularly options that specifically target the pathogenic mechanisms of this microbe. The ability of a pathogenic bacterium to cause disease is dependent upon the production of agents termed 'virulence factors', and approaches to mitigate these agents have gained increasing attention as new antibacterial strategies...
October 20, 2016: Virulence
David F Woodward, Stacey L Wenthur, Tara L Rudebush, Shan Fan, Carol B Toris
PURPOSE: Since all prostanoid receptors affect intraocular pressure (IOP) and endogenous prostanoids are found in ocular tissues, the pressor effects of prostanoid antagonists were comprehensively evaluated. The absence of effects of most of these antagonists was not entirely anticipated. To ensure no false-negative results, ocular biodisposition studies were conducted. METHODS: Monkeys with laser-induced ocular hypertension were used to study antagonist effects on IOP...
October 20, 2016: Journal of Ocular Pharmacology and Therapeutics
Lauren E Arthur, Russell S Kizor, Adrian G Selim, Mieke L van Driel, Leonardo Seoane
BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality, complicating the medical course of approximately 10% of mechanically-ventilated patients, with an estimated attributable mortality of 13%. To treat VAP empirically, the American Thoracic Society currently recommends antibiotic therapy based on the patients' risk of colonisation by an organism with multidrug resistance. The selection of initial antibiotic therapy in VAP is important, as inappropriate initial antimicrobial treatment is associated with higher mortality and longer hospital stay in intensive care unit (ICU) patients...
October 20, 2016: Cochrane Database of Systematic Reviews
Madhukar Pai, Mark P Nicol, Catharina C Boehme
Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement...
October 2016: Microbiology Spectrum
Ronit Weisman
All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases...
October 2016: Microbiology Spectrum
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