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- Strakova, A., et al.
(författare)
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Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
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- Caglar, K, et al.
(författare)
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Serum fetuin-a concentration and endothelial dysfunction in chronic kidney disease
- 2008
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Ingår i: Nephron. Clinical practice. - : S. Karger AG. - 1660-2110. ; 108:3, s. C233-C240
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Defective endothelial function, an initial step in the development of atherosclerotic plaque, is prevalent in moderate to advanced chronic kidney disease (CKD). In this study, the investigators hypothesized that fetuin-A, a calcification inhibitor, is a novel risk factor for the development of endothelial dysfunction in patients. <i>Methods:</i> 198 nondiabetic patients with a mean age of 44.0 ± 12.4 years and with different stages of CKD were studied. In addition to a detailed metabolic panel, flow-mediated dilatation assessed by high-resolution brachial ultrasonography was performed to determine endothelial dysfunction. Carotid intima-media thickness was also estimated by ultrasonography. Serum fetuin-A concentrations were determined by using a human ELISA method. <i>Results:</i> Endothelial dysfunction was observed in all stages (1–5) of CKD and worsened in parallel to the reduction in estimated glomerular filtration rate. Serum fetuin-A concentrations were also found to be decreased in all but stage 1 CKD. On multiple regression analysis, endothelial dysfunction was independently associated with fetuin-A (β = 0.745, p < 0.001) and intact parathyroid hormone concentrations (β = –0.216, p < 0.001). <i>Conclusion:</i> These data in a selected cohort of CKD patients indicate that fetuin-A may be one of the contributing factors for the development of endothelial dysfunction in CKD patients.
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- de Bruijn, Winnie, et al.
(författare)
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Introduction and Utilization of High Priced HCV Medicines across Europe : Implications for the Future
- 2016
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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