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controlled drug screening tests

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https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#1
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28429053/self-assessment-of-treatment-compliance-with-antimuscarinic-drugs-and-lower-urinary-tract-condition-among-women-with-urinary-incontinence
#2
Kirill Kosilov, Sergey Loparev, Irina Kuzina, Olga Shakirova, Natalya Zhuravskaya, Alexandra Lobodenko
AIM: Our aim was to determine the efficiency of the Medication Compliance Self-Report Inventory (MASRI) in self-reporting antimuscarinic drug treatment compliance among women with urinary incontinence (UI). MATERIALS AND METHODS: The study assessed 347 women aged 18-65 (averaging 49.7) years with more than one urinary incontinence (UI) episode per day. Treatment compliance was tested at the beginning and at weeks 4, 8, and 12 using the MASRI, the Brief Medication Questionnaire (BMQ), and visual pill counts...
April 20, 2017: International Urogynecology Journal
https://www.readbyqxmd.com/read/28426815/using-controlled-attenuation-parameter-combined-with-ultrasound-to-survey-non-alcoholic-fatty-liver-disease-in-hemodialysis-patients-a-prospective-cohort-study
#3
Yi-Hao Yen, Jin-Bor Chen, Ben-Chung Cheng, Jung-Fu Chen, Kuo-Chin Chang, Po-Lin Tseng, Cheng-Kun Wu, Ming-Chao Tsai, Ming-Tsung Lin, Tsung-Hui Hu
BACKGROUND AND AIMS: Controlled attenuation parameter (CAP) is a non-invasive method for measuring hepatic steatosis (HS). Non-alcoholic fatty liver disease (NAFLD) is closely related to cardiovascular diseases (CVDs). CVDs are the leading cause of morbidity and mortality in hemodialysis patients. The aim of this study was to investigate the prevalence of NAFLD in hemodialysis patients. METHOD: We prospectively enrolled patients undergoing chronic hemodialysis, as well as patients with normal renal function who served as controls...
2017: PloS One
https://www.readbyqxmd.com/read/28420604/a-digital-tool-to-promote-alcohol-and-drug-use-screening-brief-intervention-and-referral-to-treatment-skill-translation-a-mobile-app-development-and-randomized-controlled-trial-protocol
#4
Derek D Satre, Khanh Ly, Maria Wamsley, Alexa Curtis, Jason Satterfield
BACKGROUND: Translation of knowledge and skills from classroom settings to clinical practice is a major challenge in healthcare training, especially for behavioral interventions. For example, screening, brief intervention, and referral to treatment (SBIRT) is a highly-promoted approach to identifying and treating individuals at risk for alcohol or drug problems, yet effective, routine use of SBIRT has lagged. OBJECTIVE: The objective of this paper is to describe the development, pilot testing, and trial protocol of a mobile app based on the theory of planned behavior (TPB) to promote SBIRT skill translation and application...
April 18, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28418984/anger-and-quality-of-life-in-patients-co-infected-with-hiv-and-hepatitis-c-virus-a-cross-sectional-study-anrs-co13-hepavih
#5
Fabienne Marcellin, Camelia Protopopescu, Laure Esterle, Linda Wittkop, Lionel Piroth, Hugues Aumaitre, Olivier Bouchaud, Cécile Goujard, Daniel Vittecoq, François Dabis, Dominique Salmon-Ceron, Bruno Spire, Perrine Roux, Maria P Carrieri
OBJECTIVE: The aim of this study is to document the relationship between anger dimensions (state, trait, expression, and control) and quality of life (QoL) in patients co-infected with HIV and hepatitis C virus (HCV). PATIENTS AND METHODS: This is a cross-sectional study nested in the ANRS CO13-HEPAVIH French national cohort. Anger and QoL were assessed using self-administered questionnaires in 536 HIV-HCV-co-infected patients. Correlations between anger scores (STAXI-2 scale) and QoL scores (WHOQOL-HIV BREF scale) were assessed using Spearman's coefficients...
April 17, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28412732/small-molecule-inhibitor-screening-identifified-hsp90-inhibitor-17-aag-as-potential-therapeutic-agent-for-gallbladder-cancer
#6
Helga Weber, José R Valbuena, Mustafa A Barbhuiya, Stefan Stein, Hana Kunkel, Patricia García, Carolina Bizama, Ismael Riquelme, Jaime A Espinoza, Stephen E Kurtz, Jeffrey W Tyner, Juan Francisco Calderon, Alejandro H Corvalán, Manuel Grez, Akhilesh Pandey, Pamela Leal-Rojas, Juan C Roa
Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410582/metronidazole-for-the-treatment-of-tritrichomonas-foetus-in-bulls
#7
David Love, Virginia R Fajt, Thomas Hairgrove, Meredyth Jones, James A Thompson
BACKGROUND: Tritrichomonas foetus is a sexually transmitted protozoon that causes reproductive failure, among cattle, so disruptive that many western US states have initiated control programs. Current control programs are based on the testing and exclusion of individual bulls. Unfortunately, these programs are utilizing screening tests that are lacking in sensitivity. Blanket treatment of all the exposed bulls and adequate sexual rest for the exposed cows could provide a more viable disease control option...
April 14, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28404504/burden-of-asymptomatic-malaria-among-a-tribal-population-in-a-forested-village-of-central-india-a%C3%A2-hidden-challenge-for-malaria-control-in-india
#8
M K Chourasia, K Raghavendra, R M Bhatt, D K Swain, N Valecha, I Kleinschmidt
OBJECTIVE: Chhattisgarh in India is a malaria-endemic state with seven southern districts that contributes approximately 50-60% of the reported malaria cases in the state every year. The problem is further complicated due to asymptomatic malaria cases which are largely responsible for persistent transmission. This study was undertaken in one of the forested villages of the Keshkal subdistrict in Kondagaon district to ascertain the proportion of the population harbouring subclinical malarial infections...
March 21, 2017: Public Health
https://www.readbyqxmd.com/read/28404233/molecular-detection-of-drug-resistance-to-ofloxacin-and-kanamycin-in-mycobacterium-tuberculosis-by-using-multiplex-allele-specific-pcr
#9
Richa Kumari, Tuhina Banerjee, Shampa Anupurba
Drug resistance in tuberculosis (TB) is the biggest global health challenge as it hinders the tuberculosis control program and makes the disease more worsen. Molecular methods interrupt the spread of drug resistance by facilitating the appropriate anti- tuberculosis therapy at correct time through rapid diagnosis of multi drug resistant (MDR) and extensively drug resistant tuberculosis (XDR-TB). In this study we standardized and evaluated the diagnostic utility of multiplex allele specific PCR (MAS-PCR) targeting gyrA D94G and rrs A1401G mutations for detection of resistance against two key drugs (ofloxacin and kanamycin) of second line anti tuberculosis treatment...
April 9, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28399844/implementation-of-a-pragmatic-randomized-trial-of-screening-for-chronic-kidney-disease-to-improve-care-among-non-diabetic-hypertensive-veterans
#10
Carmen A Peralta, Martin Frigaard, Anna D Rubinsky, Leticia Rolon, Lowell Lo, Santhi Voora, Karen Seal, Delphine Tuot, Shirley Chao, Kimberly Lui, Phillip Chiao, Neil Powe, Michael Shlipak
BACKGROUND: Whether screening for chronic kidney disease (CKD) can improve the care of persons at high risk for complications remains uncertain. We describe the design and early implementation experience of a pilot, cluster-randomized pragmatic trial to evaluate the feasibility, implementation, and effectiveness of a "triple marker" CKD screening program (creatinine, cystatin C and albumin to creatinine ratio) for improving care among hypertensive veterans seen in primary care at one Veterans Administration Hospital...
April 12, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28378767/the-need-to-compare-assessing-the-level-of-agreement-of-three-high-throughput-assays-against-plasmodium-falciparum-mature-gametocytes
#11
Leonardo Lucantoni, Sasdekumar Loganathan, Vicky M Avery
Whole-cell High-Throughput Screening (HTS) is a key tool for the discovery of much needed malaria transmission blocking drugs. Discrepancies in the reported outcomes from various HTS Plasmodium falciparum gametocytocidal assays hinder the direct comparison of data and ultimately the interpretation of the transmission blocking potential of hits. To dissect the underlying determinants of such discrepancies and assess the impact that assay-specific factors have on transmission-blocking predictivity, a 39-compound subset from the Medicines for Malaria Venture Malaria Box was tested in parallel against three distinct mature stage gametocytocidal assays, under strictly controlled parasitological, chemical, temporal and analytical conditions resembling the standard membrane feeding assay (SMFA)...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28378146/use-of-a-highly-parallel-microfluidic-flow-cell-array-to-determine-therapeutic-drug-dose-response-curves
#12
Jesús A Arellano, Taylor A Howell, James Gammon, Sungpil Cho, Margit M Janát-Amsbury, Bruce Gale
A high-throughput, microfluidic flow cell array (MFCA) system has been modified to enable drug screening against small-volume cell-, and tissue cultures. The MFCA is composed of a 3D channel network that simultaneously flows fluids through forty-eight 830 μm by 500 μm flow cells, which physically divide and fluidically seal an existing culture into multiple compartments when docked onto the surface of a cell or tissue culture dish. The modified system provides temperature (37 °C) and CO2/pH level controls, while continuously flowing solutions (media or other liquid such as drug suspensions) over the cells/tissues...
June 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28376796/ahcoda-db-a-data-repository-with-web-based-mining-tools-for-the-analysis-of-automated-high-content-mouse-phenomics-data
#13
Bastijn Koopmans, August B Smit, Matthijs Verhage, Maarten Loos
BACKGROUND: Systematic, standardized and in-depth phenotyping and data analyses of rodent behaviour empowers gene-function studies, drug testing and therapy design. However, no data repositories are currently available for standardized quality control, data analysis and mining at the resolution of individual mice. DESCRIPTION: Here, we present AHCODA-DB, a public data repository with standardized quality control and exclusion criteria aimed to enhance robustness of data, enabled with web-based mining tools for the analysis of individually and group-wise collected mouse phenotypic data...
April 4, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28367020/comparison-of-four-phenotypic-methods-for-detection-of-metallo-%C3%AE-lactamase-producing-gram-negative-bacteria-in-rural-teaching-hospital
#14
Chinjal A Panchal, Sweta Sunil Oza, Sanjay J Mehta
CONTEXT: Metallo-β-lactamase (MBL)-producing bacteria lead to resistance to carbapenem an antibiotic that used as the last resort for treatment of multidrug-resistant bacteria, extended spectrum beta-lactamases, and AmpC β-lactamase-producing Gram-negative bacteria (GNB). The emergence of MBL-producing GNB is challenge to microbiology laboratories because there are no standardized guidelines available to detect them. The aim of this study was to compare four phenotypic methods to detect MBL production in GNB and to determine antibiotic sensitivity of MBL-producing isolates...
April 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28366666/a-high-content-microscopy-assay-to-determine-drug-activity-against-intracellular-mycobacterium-tuberculosis
#15
Alyssa J Manning, Yulia Ovechkina, Amanda McGillivray, Lindsay Flint, David M Roberts, Tanya Parish
Tuberculosis is one of the infectious diseases with the greatest global burden, affecting millions of people. The rise of multi- and extensively-drug resistant forms of Mycobacterium tuberculosis over the last few decades has highlighted the urgent need for development of new drugs to treat the disease. Many drug development pipelines are based on in vitro assays examining a compound's effect on M. tuberculosis alone. These do not account for the effect of a compound on mammalian cells nor the interaction between host and pathogen...
March 31, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28357131/aquatic-therapy-for-boys-with-duchenne-muscular-dystrophy-dmd-an-external-pilot-randomised-controlled-trial
#16
Daniel Hind, James Parkin, Victoria Whitworth, Saleema Rex, Tracey Young, Lisa Hampson, Jennie Sheehan, Chin Maguire, Hannah Cantrill, Elaine Scott, Heather Epps, Marion Main, Michelle Geary, Heather McMurchie, Lindsey Pallant, Daniel Woods, Jennifer Freeman, Ellen Lee, Michelle Eagle, Tracey Willis, Francesco Muntoni, Peter Baxter
BACKGROUND: Standard treatment of Duchenne muscular dystrophy (DMD) includes regular physiotherapy. There are no data to show whether adding aquatic therapy (AT) to land-based exercises helps maintain motor function. We assessed the feasibility of recruiting and collecting data from boys with DMD in a parallel-group pilot randomised trial (primary objective), also assessing how intervention and trial procedures work. METHODS: Ambulant boys with DMD aged 7-16 years established on steroids, with North Star Ambulatory Assessment (NSAA) score ≥8, who were able to complete a 10-m walk test without aids or assistance, were randomly allocated (1:1) to 6 months of either optimised land-based exercises 4 to 6 days/week, defined by local community physiotherapists, or the same 4 days/week plus AT 2 days/week...
2017: Pilot and Feasibility Studies
https://www.readbyqxmd.com/read/28346100/robotic-mammosphere-assay-for-high-throughput-screening-in-triple-negative-breast-cancer
#17
P A Fitzpatrick, N Akrap, E M V Söderberg, H Harrison, G J Thomson, G Landberg
In order to identify novel treatment principles specifically affecting cancer stem cells in triple-negative breast cancer, we have developed a high-throughput screening method based on the mammosphere and anoikis resistance assays allowing us to screen compounds using a functional readout. The assay was validated against manual protocols and through the use of positive controls, such as the response to hypoxia and treatment with the known cancer stem cell-targeting compound salinomycin. Manual and robotic procedures were compared and produced similar results in cell handling, cell cultures, and counting techniques, with no statistically significant difference produced from either method...
February 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28342672/an-in-vitro-larval-migration-assay-for-assessing-anthelmintic-activity-of-different-drug-classes-against-ascaris-suum
#18
Jianguo Zhao, Andrew R Williams, Tina Vicky Alstrup Hansen, Stig M Thamsborg, Jianping Cai, Shuaibao Song, Gang Chen, Ming Kang, Zhuangzhi Zhang, Qun Liu, Qian Han
In vitro methods have been developed for the detection of anthelmintic resistance in a range of nematode species. However, the life cycle of Ascaris suum renders the commonly used egg hatch assay and larval development assay unusable. In this study we developed a combined multi-well culture and agar gel larval migration assay to test the effect of benzimidazole and tetrahydropyrimidin/imidazothiazole anthelmintics against nine isolates of A. suum collected from locations in China and Denmark. Drugs tested were thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel...
March 18, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28342321/improvement-of-paracellular-transport-in-the-caco-2-drug-screening-model-using-protein-engineered-substrates
#19
Rebecca L DiMarco, Daniel R Hunt, Ruby E Dewi, Sarah C Heilshorn
The Caco-2 assay has achieved wide popularity among pharmaceutical companies in the past two decades as an in vitro method for estimation of in vivo oral bioavailability of pharmaceutical compounds during preclinical characterization. Despite its popularity, this assay suffers from a severe underprediction of the transport of drugs which are absorbed paracellularly, that is, which pass through the cell-cell tight junctions of the absorptive cells of the small intestine. Here, we propose that simply replacing the collagen I matrix employed in the standard Caco-2 assay with an engineered matrix, we can control cell morphology and hence regulate the cell-cell junctions that dictate paracellular transport...
March 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28336905/a-nanostructured-matrices-assessment-to-study-drug-distribution-in-solid-tumor-tissues-by-mass-spectrometry-imaging
#20
Silvia Giordano, Valentina Pifferi, Lavinia Morosi, Melinda Morelli, Luigi Falciola, Giuseppe Cappelletti, Sonja Visentin, Simonetta A Licandro, Roberta Frapolli, Massimo Zucchetti, Roberta Pastorelli, Laura Brunelli, Maurizio D'Incalci, Enrico Davoli
The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties...
March 21, 2017: Nanomaterials
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