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  • 1. de Bruijn, Winnie
    et al.
    Ibanez, Cristina
    Frisk, Pia
    Pedersen, Hanne Bak
    Alkan, Ali
    Bonanno, Patricia Vella
    Brkicic, Ljiljana S.
    Bucsicsa, Anna
    Dedet, Guillaume
    Eriksen, Jaran
    Fadare, Joseph O.
    Furst, Jurij
    Gallego, Gisselle
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. School of Medicine, The University of Notre Dame Australia, Darlinghurst, NSW, Australia.
    Godoi, Isabella P.
    Guerra Junior, Augusto A.
    Gursoz, Hakki
    Jan, Saira
    Jones, Jan
    Joppi, Roberta
    Kerman, Saim
    Laius, Ott
    Madzikwa, Newman
    Magnusson, Einar
    Maticic, Mojca
    Markovic-Pekovic, Vanda
    Massele, Amos
    Ogunleye, Olayinka
    O'Leary, Aisling
    Piessnegger, Jutta
    Sermet, Catherine
    Simoens, Steven
    Tiroyakgosi, Celda
    Truter, Ilse
    Thyberg, Magnus
    Tomekova, Kristina
    Wladysiuk, Magdalena
    Vandoros, Sotiris
    Vural, Elif H.
    Zara, Corinne
    Godman, Brian
    Introduction and Utilization of High Priced HCV Medicines across Europe: Implications for the Future2016In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 7, article id 197Article in journal (Refereed)
    Abstract [en]

    Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (Hs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIEN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIOs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new Pls vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes monitored in the future to provide additional guidance.

  • 2. Lallement, Pierre-Alexandre
    et al.
    Brouwer, Bastiaan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Keech, Olivier
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hecker, Arnaud
    Rouhier, Nicolas
    The still mysterious roles of cysteine-containing glutathione transferases in plants2014In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 5, p. 192-Article, review/survey (Refereed)
    Abstract [en]

    Glutathione transferases (GSTs) represent a widespread multigenic enzyme family able to modify a broad range of molecules. These notably include secondary metabolites and exogenous substrates often referred to as xenobiotics, usually for their detoxification, subsequent transport or export. To achieve this, these enzymes can bind non-substrate ligands (ligandin function) and/or catalyze the conjugation of glutathione onto the targeted molecules, the latter activity being exhibited by GSTs having a serine or a tyrosine as catalytic residues. Besides, other GST members possess a catalytic cysteine residue, a substitution that radically changes enzyme properties. Instead of promoting GSH-conjugation reactions, cysteine-containing GSTs (Cys-GSTs) are able to perform deglutathionylation reactions similarly to glutaredoxins but the targets are usually different since glutaredoxin substrates are mostly oxidized proteins and Cys-GST substrates are metabolites. The Cys-GSTs are found in most organisms and form several classes. While Beta and Omega GSTs and chloride intracellular channel proteins (CLICs) are not found in plants, these organisms possess microsomal ProstaGlandin E-Synthase type 2, glutathionyl hydroquinone reductases, Lambda, Iota and Hemerythrin GSTs and dehydroascorbate reductases (DHARs); the four last classes being restricted to the green lineage. In plants, whereas the role of DHARs is clearly associated to the reduction of dehydroascorbate to ascorbate, the physiological roles of other Cys-GSTs remain largely unknown. In this context, a genomic and phylogenetic analysis of Cys-GSTs in photosynthetic organisms provides an updated classification that is discussed in the light of the recent literature about the functional and structural properties of Cys-GSTs. Considering the antioxidant potencies of phenolic compounds and more generally of secondary metabolites, the connection of GSTs with secondary metabolism may be interesting from a pharmacological perspective.

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