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drug screening

Jesus Eric Piña-Garza, Danielle Boyce, David M Tworek, Kathryn A Davis, Heather Gatens, George Lai, Patricia E McGoldrick, Bethany Thomas, Steven M Wolf
BACKGROUND: The complex clinical presentation and progression of Lennox-Gastaut syndrome (LGS) can complicate the accurate diagnosis of this severe, lifelong, childhood-onset epilepsy, often resulting in suboptimal treatment. The Refractory Epilepsy Screening Tool for LGS (REST-LGS) was developed to improve the identification of patients with LGS. METHODS: Using the Modified Delphi Consensus, a group of experts developed and tested the REST-LGS Case Report Form (CRF) comprising 8 criteria (4 major, 4 minor) considered potentially indicative of LGS...
December 8, 2018: Epilepsy & Behavior: E&B
Amanda Balboni Iniguez, Gabriela Alexe, Emily Jue Wang, Giovanni Roti, Sarvagna Patel, Liying Chen, Samuel Kitara, Amy Conway, Amanda L Robichaud, Björn Stolte, Pratiti Bandopadhayay, Amy Goodale, Sasha Pantel, Yenarae Lee, Dorian M Cheff, Matthew D Hall, Rajarshi Guha, Mindy I Davis, Marie Menard, Nicole Nasholm, William A Weiss, Jun Qi, Rameen Beroukhim, Federica Piccioni, Cory Johannessen, Kimberly Stegmaier
Drug resistance represents a major challenge to achieving durable responses to cancer therapeutics. Resistance mechanisms to epigenetically targeted drugs remain largely unexplored. We used bromodomain and extra-terminal domain (BET) inhibition in neuroblastoma as a prototype to model resistance to chromatin modulatory therapeutics. Genome-scale, pooled lentiviral open reading frame (ORF) and CRISPR knockout rescue screens nominated the phosphatidylinositol 3-kinase (PI3K) pathway as promoting resistance to BET inhibition...
December 10, 2018: Cancer Cell
Elizabeth L Robinson, Edward Sisco
In recent months, there has been increased reporting of seized drug and toxicology cases containing rodenticides, the active ingredient in rat poisons. Seeing as rodenticides are not scheduled substances, they are not commonly screened for in seized drug analysis. This work investigates the use of TD-DART-MS for the simultaneous detection of rodenticides and drugs. Six rodenticides were evaluated, an optimal method was established, and limits of detection in the tens of nanograms were calculated. Additional studies highlight that detection at less than 1% by weight in mixtures with AB-FUBINACA, cocaine, heroin, or methamphetamine was possible...
December 10, 2018: Journal of Forensic Sciences
Yusuke Okuma, Kei Morikawa, Hisashi Tanaka, Takuma Yokoyama, Hidetoshi Itani, Kazuya Horiuchi, Hideyuki Nakagawa, Nobumasa Takahashi, Akihiro Bessho, Kenzo Soejima, Kazuma Kishi, Akira Togashi, Yae Kanai, Koji Ueda, Katsuhisa Horimoto, Noriyuki Matsutani, Nobuhiko Seki
Patients with EGFR-mutated non-small cell lung cancer (NSCLC) exhibit resistance to EGFR-tyrosine kinase inhibitors (TKIs) within 9-14 months of therapy. Recently, EGFR-mutated NSCLC has demonstrated the potential for heterogeneity; therefore, the manner of clonal heterogeneity may impact the duration of progression-free and overall survival and other parameters affecting EGFR-TKI treatment efficacy. However no predictive biomarker of these favorable treatment efficacies has been identified to date. The exosome-focused translational research for afatinib (EXTRA) study aims to identify a novel predictive biomarker and a resistance marker for afatinib by analyzing data from association studies of the clinical efficacy of afatinib and four "OMICs" (genomics, proteomics, epigenomics, and metabolomics) using peripheral blood from patients treated with afatinib...
December 8, 2018: Thoracic Cancer
Xiao-Dong Geng, Wei-Wei Wang, Zhe Feng, Ran Liu, Xiao-Long Cheng, Wan-Jun Shen, Zhe-Yi Dong, Guang-Yan Cai, Xiang-Mei Chen, Quan Hong, Di Wu
AIMS: The aim of the study is to identify candidate differentially expressed genes (DEGs) and pathways using bioinformatics analysis and improve our understanding of the cause and potential molecular events of diabetic nephropathy (DN). MATERIALS AND METHODS: Two cohort profile datasets (GSE30528 and GSE33744) were integrated and used for deep analysis. We sorted DEGs and analyzed differential pathway enrichment. DEG-associated ingenuity pathway analysis (IPA) was performed...
December 9, 2018: Journal of Diabetes Investigation
V Krishnan Ramanujan
Cancer cells are known to display a variety of metabolic reprogramming strategies to fulfill their own growth and proliferative agenda. With the advent of high resolution imaging strategies, metabolomics techniques, and so forth, there is an increasing appreciation of critical role that tumor cell metabolism plays in the overall breast cancer (BC) growth. In this report, we demonstrate a sensitive, flow-cytometry-based assay for rapidly assessing the metabolic phenotypes in isolated suspensions of breast cancer cells...
December 11, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Ludovit Schreiber, Martin Morovič, Katarína Špacayová, Radoslav Halko
A case of suspected acute and lethal intoxication caused by colchicine has been reported. The woman was hospitalized after her suspicion of suicidal poisoning by a rare autumn crocus (Colchicum autumnale). Suspected colchicine poisoning was confirmed using a novel UHPLC method with a modern reversed-phase stationary phase with a sub 2-micron superficial porous particle size combined with a QTOF mass spectrometer. Sample preparation procedure included the addition of propiverine as internal standard, protein precipitation using methanol and solid phase extraction...
December 10, 2018: Journal of Forensic Sciences
Zhenxi Li, Jinping Huang, Fanhua Wang, Wenjun Li, Xian Wu, Chenglong Zhao, Jian Zhao, Haifeng Wei, Zhipeng Wu, Ming Qian, Peng Sun, Liang He, Yunyun Jin, Jie Tang, Wenwei Qiu, Stefan Siwko, Mingyao Liu, Jian Luo, Jianru Xiao
Osteoporosis is a global bone disease characterized by reduced bone mineral density (BMD) and increased risk of fractures. The risk of developing osteoporosis increases with aging, especially after menopause in women. Discovering the signaling pathways which play a significant role in aging- and menopause-induced osteoporosis should accelerate osteoporosis drug discovery. In this study, we found that bile acid membrane receptor Tgr5 knockout C57BL/6J mice had similar bone mass as wild type mice during early and middle age (before 4 months old) bone remodeling; however, Tgr5-/- markedly decreased bone mass in aged (more than 7 months old) and ovariectomized (OVX) mice compared with wild type mice...
December 7, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
L Del Pup, F A Peccatori, P E Levi-Setti, G Codacci-Pisanelli, P Patrizio
OBJECTIVE: Infertile women requiring ovarian stimulation and assisted reproduction techniques (ART) are faced with difficult issues. The fear that using hormones could increase their risk of cancer is the most significant. One of the main challenges for assessing cancer risk after ART is the difficulty to separate it from the underlying condition of infertility per se. The delay or the inability to achieve a pregnancy is an important risk factor for breast, endometrial and ovarian cancer...
November 2018: European Review for Medical and Pharmacological Sciences
Christina Mohr Jensen, Torben Breindahl
The use of medicines to treat attention deficit/hyperactivity disorder (ADHD) has increased worldwide, including the use of amphetamine-based medicines or prodrugs that metabolise to amphetamine in vivo. At the same time, drugs-of-abuse testing by non-specific, point-of-care immunoassay methods ('quick tests') has increased. This article discusses the risk of 'false positive' results or post-analytical misinterpretations of results when immunoassays are used to analyse biological samples from ADHD patients...
December 7, 2018: Attention Deficit and Hyperactivity Disorders
Avril A B Robertson
Modulation of inflammasomes has tremendous therapeutic potential and is hotly pursued by industry and academia alike. Indeed a growing number of patents are emerging to protect the intellectual property in valuable compound classes. This chapter focusses specifically on the suite of small-molecule NLRP3 inflammasome inhibitors published, as specific modulation of other inflammasomes is not yet well established. Synthetic molecules, known drugs and natural product NLRP3 modulators will be detailed. Some of the molecular classes discussed have been extensively characterised through cell-based screening, pharmacokinetic profiling and therapeutic proof of concept animal models...
2018: Experientia. Supplementum
Pengyu Huang, Lulu Sun, Ludi Zhang, Lijian Hui
Primary hepatocytes are widely used in regenerative medicine, drug metabolism analysis, and in vitro drug screens. To overcome the shortage of liver donors, several strategies, such as differentiation of pluripotent stem cells and transdifferentiation from somatic cells, were developed to generate hepatocytes from alternative sources. Here, we describe in detail lenti-virus-based procedure for direct conversion of human fibroblasts to hepatocytes (hiHep cells) in vitro. A detailed protocol for preparation of human fibroblasts from scar tissues is also provided...
2019: Methods in Molecular Biology
Muhammad Nadeem Ashraf, Muhammad Waheed Asghar, Yan Rong, Michael R Doschak, Tony K L Kiang
Several HepaRG three-dimensional (3D) in vitro model systems have been developed to improve the predictability of xenobiotic metabolism and toxicity. In this review, we present a detailed summary and critique of the performance of various HepaRG 3D models compared to the conventional 2D monolayer culture. HepaRG 3D models can be broadly categorized into (1) scaffold-free, (2) scaffold-based, and (3) bioartificial liver (BAL) models. With respect to the scaffold-free configurations, the hanging drop model closely mimics the normal physiological function and metabolic profile of the liver...
December 10, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Lauren M Hill, Carol E Golin, Nisha C Gottfredson, Brian W Pence, Bethany DiPrete, Jessica Carda-Auten, Jennifer S Groves, Sonia Napravnik, David Wohl, Kevin Knight, Patrick M Flynn
Depression is a known risk factor for antiretroviral therapy (ART) non-adherence, but little is known about the mechanisms explaining this relationship. Identifying these mechanisms among people living with HIV (PLHIV) after release from prison is particularly important, as individuals during this critical period are at high risk for both depression and poor ART adherence. 347 PLHIV recently released from prison in North Carolina and Texas were included in analyses to assess mediation of the relationship between depressive symptoms at 2 weeks post-release and ART adherence (assessed by unannounced telephone pill counts) at weeks 9-21 post-release by the hypothesized explanatory mechanisms of alcohol use, drug use, adherence self-efficacy, and adherence motivation (measured at weeks 6 and 14 post-release)...
December 7, 2018: AIDS and Behavior
Ann-Katrin Kraeuter, Paul C Guest, Zoltán Sarnyai
The open field test is used in studies of the neurobiological basis of anxiety and screening for novel drug targets and anxiolytic compounds. This test uses a camera to measure movement of the test animal in the peripheral and central zones of a 42 × 42 × 42 cm polyvinyl chloride box. This chapter describes a protocol for carrying out the open-field test for assessment of locomotion and anxiety-like behavior in mice.
2019: Methods in Molecular Biology
Víctor Sorribas, Natalia Guillén, Cecilia Sosa
The control of inorganic phosphate homeostasis is mediated through the activity of sodium-coupled Pi transporters located in the intestine, kidneys, and bone. To study these transporters in either the native tissue or after heterologous expression, it is very important to use specific inhibitors of the studied transporter, in order to know the corresponding relevance in the total Pi uptake and to differentiate from the activity of other transporters. Inhibitors are also necessary as drugs for treating Pi homeostasis disorders...
December 7, 2018: Pflügers Archiv: European Journal of Physiology
Yoshitaka Nishikawa, Ayako Kohno, Yoshimitsu Takahashi, Chiaki Suzuki, Hirokatsu Kinoshita, Takeo Nakayama, Masaharu Tsubokura
Context: Intake of stable iodine helps prevent childhood thyroid cancer in nuclear emergencies but there is limited case information. Objective: We identified the intake rate and the factors associated with no intake among children who did not take stable iodine after the Fukushima disaster. Design: Retrospective observational study. Setting: Data were obtained from thyroid cancer screening performed in August-November 2017...
December 10, 2018: Journal of Clinical Endocrinology and Metabolism
Katsuyoshi Matsunami
Caenorhabditis elegans has been used in research for years to clarify the genetic cascades and molecular mechanisms of aging, longevity, and health span. Health span is closely related to frailty; however, frailty has a different concept and is evaluated using various parameters in humans, such as Fried's Frailty Criteria. The C. elegans model has several advantages when performing a chemical screen to identify drug candidates. Several mouse models of frailty were recently developed, including a homozygous IL-10 knockout...
2018: Frontiers in Nutrition
Brennan Marsh-Armstrong, Jesse M Fajnzylber, Samuel Korntner, Bailey A Plaman, Anthony C Bishop
Difficulties in developing active-site-directed protein tyrosine phosphatase (PTP) inhibitors have led to the perception that PTPs are "undruggable", highlighting the need for new means to target pharmaceutically important PTPs allosterically. Recently, we characterized an allosteric-inhibition site on the PTP domain of Src-homology-2-domain-containing PTP 2 (SHP2), a key anticancer drug target. The central feature of SHP2's allosteric site is a nonconserved cysteine residue (C333) that can potentially be labeled with electrophilic compounds for selective SHP2 inhibition...
November 30, 2018: ACS Omega
Brian R Schultz, Brett Y Lu, Jane M Onoye, Tara P Toohey
Methamphetamine use has increased throughout the United States in recent years, and is historically prevalent in Hawai'i. This retrospective study aimed to determine the effect of methamphetamine use on emergency department (ED) resources, by examining visits to an emergency department (ED) in an urban hospital in Hawai'i from 2007 - 2011. The rate of patients who tested positive for amphetamine was measured and broken down by year. Primary outcomes included length of ED stay, the administration of medication or physical restraints for safety, and the rate of psychiatric hospitalization...
December 2018: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
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