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Danielle Oliveira Dos Anjos, Eliomara Sousa Sobral Alves, Vinicius Tomaz Gonçalves, Sheila Suarez Fontes, Mateus Lima Nogueira, Ana Márcia Suarez-Fontes, João Batista Neves da Costa, Fabricio Rios-Santos, Marcos André Vannier-Santos
Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β-lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β-lapachone derivative affected the T...
October 12, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Margret Thorsteinsdottir, Unnur A Thorsteinsdottir, Finnur F Eiriksson, Hrafnhildur L Runolfsdottir, Inger M Sch Agustsdottir, Steinunn Oddsdottir, Baldur B Sigurdsson, Hordur K Hardarson, Nilesh R Kamble, Snorri Th Sigurdsson, Vidar O Edvardsson, Runolfur Palsson
Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA...
September 14, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Eric Lawitz, Fred Poordad, Julio A Gutierrez, Jennifer T Wells, Carmen E Landaverde, Barbara Evans, Anita Howe, Hsueh-Cheng Huang, Jerry Jing Li, Peggy Hwang, Frank J Dutko, Michael Robertson, Janice Wahl, Eliav Barr, Barbara Haber
Direct-acting antiviral agents (DAAs) represent the standard of care for patients with hepatitis C virus (HCV) infection. Combining DAAs with different mechanisms may allow for shorter treatment durations that are effective across multiple genotypes. The aim of the C-SWIFT study was to identify the minimum effective treatment duration across multiple genotypes. C-SWIFT was an open-label, single-center trial in treatment-naïve patients with chronic HCV genotype (GT)1 or 3 infection. All patients received elbasvir (EBR) 100 mg/grazoprevir (GZR) 50 mg with sofosbuvir (SOF) 400 mg for 4-12 weeks...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Li Zhang, Zhihong Yang, Jocelyn Trottier, Olivier Barbier, Li Wang
: Bile acids (BAs) play critical physiological functions in cholesterol homeostasis and deregulation of BA metabolism causes cholestatic liver injury. Maternally expressed gene 3 (MEG3) was recently shown as a potential tumor suppressor, however its basic hepatic function remains elusive. Using RNA pull-down with biotin-labeled sense or anti-sense MEG3RNA followed by mass spectrometry, we identified RNA binding protein polypyrimidine tract-binding protein 1 (PTBP1) as a MEG3 interaction protein and validated their interaction by RNA immunoprecipitation (RIP)...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Baptiste Brossard, Normand Carpentier
Contemporary research into health and mental health treats diagnosis as a central step in understanding illness management and trajectory; consequently, in the last two decades, sociology of diagnosis has attained increasing influence within medical sociology. Deeply embedded in social constructionism, the set of research divides between those who focus on the social and historical construction of diagnoses as categories, and those who see diagnosis as a process. Regarding the latter, this approach explores the constitution of the medical production, highlighting how it constitutes a starting point for entering a 'sick role', for being labelled, for naming one's problem and by extension, for framing one's illness narrative...
October 22, 2016: Sociology of Health & Illness
Elisa Luzon, Kevin Blake, Susan Cole, Anna Nordmark, Carolien Versantvoort, Eva Gil Berglund
Physiologically-Based Pharmacokinetic (PBPK) modelling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modelling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures...
October 22, 2016: Clinical Pharmacology and Therapeutics
Mathias Kranz, Bernhard Sattler, Solveig Tiepolt, Stephan Wilke, Winnie Deuther-Conrad, Cornelius K Donat, Steffen Fischer, Marianne Patt, Andreas Schildan, Jörg Patt, René Smits, Alexander Hoepping, Jörg Steinbach, Osama Sabri, Peter Brust
BACKGROUND: Both enantiomers of [(18)F]flubatine are new radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[(18)F]flubatine compared to (-)-[(18)F]flubatine was its higher binding affinity suggesting that (+)-[(18)F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (-)-[(18)F]flubatine in early stages of Alzheimer's disease...
December 2016: EJNMMI Physics
Motahare Soufi, Alireza Kamali-Asl, Parham Geramifar, Arman Rahmim
PURPOSE: Determination of intra-tumor high-uptake area using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography (PET) imaging is an important consideration for dose painting in radiation treatment applications. The aim of our study was to develop a framework towards automated segmentation and labeling of homogeneous vs. heterogeneous tumors in clinical lung [(18)F]FDG-PET with the capability of intra-tumor high-uptake region delineation. PROCEDURES: We utilized and extended a fuzzy random walk PET tumor segmentation algorithm to delineate intra-tumor high-uptake areas...
October 21, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Martine Boccara, Alexis Sarazin, Bernard Billoud, Agnes Bulski, Louise Chapell, David Baulcombe, Vincent Colot
Epigenetic response to stress in plants involves changes in DNA methylation, histone modifications, and expression of small noncoding RNAs (sRNA). Here we present the method of analysis of differential expression of sRNA populations using DNA tiling arrays. sRNA extracted from Arabidopsis thaliana plants exposed to pathogen elicitor or control plants were reverse-transcribed into cDNAs, and subsequently hybridized after labeling to a custom-made DNA tiling array covering Arabidopsis chromosome 4. We first designed a control experiment with eight cDNA clones corresponding to sequences located on chromosome 4 and obtained robust and specific hybridization signals...
2017: Methods in Molecular Biology
Benjamin Kearns, Abdullah Pandor, Matt Stevenson, Jean Hamilton, Duncan Chambers, Mark Clowes, John Graham, M Satish Kumar
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
October 22, 2016: PharmacoEconomics
Jill K Logan, Hardin Pantle
PURPOSE: The role of topical tranexamic acid in the management of anterior epistaxis in adult patients in the emergency department (ED) is examined. SUMMARY: The use of alternative agents for the treatment of epistaxis before the use of nasal packing may be reasonable due to patient discomfort, potential complications, and the need for follow-up with a healthcare provider for packing removal. One such agent is tranexamic acid. Two published studies evaluated the off-label use of topical tranexamic acid for the treatment of epistaxis...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Uma Mahadevan, Ryan A McConnell, Christina Chambers
The management of the pregnant patient with inflammatory bowel disease (IBD) is complicated by multiple providers, misinformation and a disease entity that, particularly when active, can adversely affect pregnancy outcomes. This paper seeks to frame the debate on medication safety in pregnancy and lactation using the Food and Drug Administration's new Pregnancy and Lactation Labeling Rule (PLLR) and the most up to date safety information to discuss the risks and benefits of using each class of IBD medication...
October 18, 2016: Gastroenterology
Emilie Hein Zobel, Bernt Johan von Scholten, Morten Lindhardt, Frederik Persson, Tine Willum Hansen, Peter Rossing
AIMS/HYPOTHESIS: Management of diabetic nephropathy includes reduction of albuminuria, blood pressure and weight. The GLP-1 receptor agonist liraglutide may possess these pleiotropic effects in addition to the glucose lowering effect. We aimed to elucidate the individual liraglutide treatment response by determining if high responders (highest reduction) in each risk factor also had high response in other renal risk factors (cross-dependency). METHODS: Open-label study: 31 type 2 diabetics treated with liraglutide for 7weeks...
September 30, 2016: Journal of Diabetes and its Complications
Andrew Bottomley, Madeline Pe, Jeff Sloan, Ethan Basch, Franck Bonnetain, Melanie Calvert, Alicyn Campbell, Charles Cleeland, Kim Cocks, Laurence Collette, Amylou C Dueck, Nancy Devlin, Hans-Henning Flechtner, Carolyn Gotay, Eva Greimel, Ingolf Griebsch, Mogens Groenvold, Jean-Francois Hamel, Madeleine King, Paul G Kluetz, Michael Koller, Daniel C Malone, Francesca Martinelli, Sandra A Mitchell, Carol M Moinpour, Jammbe Musoro, Daniel O'Connor, Kathy Oliver, Elisabeth Piault-Louis, Martine Piccart, Francisco L Pimentel, Chantal Quinten, Jaap C Reijneveld, Christoph Schürmann, Ashley Wilder Smith, Katherine M Soltys, Martin J B Taphoorn, Galina Velikova, Corneel Coens
Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established...
October 18, 2016: Lancet Oncology
Pim B Olthof, Michal Heger, Krijn P van Lienden, Kora de Bruin, Roelof J Bennink, Thomas M van Gulik
BACKGROUND: Portal vein embolization is the gold standard approach to preoperatively enhance the future liver remnant before liver resection. Portal vein embolization is studied in several experimental animal models; however, clinical translation of results is often difficult. We aimed to examine the translational value of the portal vein embolization response in a standardized rabbit model by comparing the volume and function increase with the response seen in patients. METHODS: Six rabbits were subjected to embolization of the cranial liver lobes, and the hypertrophy response of the caudal liver lobe was studied using computed tomography volumetry and Technetium-99m-labeled-mebrofenin hepatobiliary scintigraphy...
October 18, 2016: Surgery
Richard J Hamilton, Vadim Keyfes, Sahil S Banka
BACKGROUND: Synthetic cannabinoids (SC) are recreational designer drugs intended to mimic delta-9-tetrahydrocannabinol while surreptitiously circumventing classification by the Drug Enforcement Administration. CASE REPORT: A 50-year-old black male arrived in the Emergency Department transported by Emergency Medical Services (EMS) for altered mental status after complaining of chest pain associated with smoking SCs. EMS found the patient with an empty foil pack labeled "Scooby Snax Limited Edition Blueberry Potpourri...
October 19, 2016: Journal of Emergency Medicine
Adey A Berhanu, Svetlana Krasnokutsky, Robert T Keenan, Michael H Pillinger
INTRODUCTION: Pegloticase is a highly effective therapy for patients with refractory and/or tophaceous gout, but has a high discontinuation rate (30-50%) due to development of anti-drug antibodies causing loss of efficacy and risk of infusion reactions. OBJECTIVE: To describe the use of azathioprine or other immunosuppressive therapies as a pegloticase adjunct to prevent pegloticase immunogenicity when treating gout. METHODS: Case report of azathioprine use in a patient receiving pegloticase therapy for refractory tophaceous gout, and review of the literature for the impact of immunosuppressive agents on development of anti-drug antibodies...
September 20, 2016: Seminars in Arthritis and Rheumatism
Jyh-Ming Liou, Yu-Jen Fang, Chieh-Chang Chen, Ming-Jong Bair, Chi-Yang Chang, Yi-Chia Lee, Mei-Jyh Chen, Chien-Chuan Chen, Cheng-Hao Tseng, Yao-Chun Hsu, Ji-Yuh Lee, Tsung-Hua Yang, Jiing-Chyuan Luo, Chun-Chao Chang, Chi-Yi Chen, Po-Yueh Chen, Chia-Tung Shun, Wen-Feng Hsu, Wen-Hao Hu, Yen-Nien Chen, Bor-Shyang Sheu, Jaw-Town Lin, Jeng-Yih Wu, Emad M El-Omar, Ming-Shiang Wu
BACKGROUND: Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. METHODS: In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan...
October 18, 2016: Lancet
Paul A Gurbel, Kevin P Bliden, Rahul Chaudhary, Jeff Patrick, Fang Liu, Gailing Chen, Christopher McLeod, Udaya S Tantry
High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162...
September 20, 2016: American Journal of Cardiology
Meng Chen, Ning Gan, You Zhou, Tianhua Li, Qing Xu, Yuting Cao, Yinji Chen
An ultrasensitive electrochemical aptasensor for simultaneous detection of oxytetracycline (OTC) and kanamycin (KAN) has been developed based on metal ions doped metal organic frame materials (MOFs) as signal tracers and RecJf exonuclease-catalyzed targets recycling amplification. The aptasensor consists of capture beads (the anti-single-stranded DNA Antibody, as anti-ssDNA Ab, labeled on Dynabeads) and nanoscale MOF (NMOF) based signal tracers (simplified as Apts-MNM, the NMOF labeled with metal ions and the aptamers)...
December 1, 2016: Talanta
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