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- Eriksson, Bengt I., 1946, et al.
(författare)
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Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development
- 2009
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Ingår i: Clin Pharmacokinet. - 0312-5963. ; 48:1, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- For the past five decades, there has been little progress in the development of oral anticoagulants, with the choices being limited to the vitamin K antagonists (VKAs). The situation is changing with the development of orally active small molecules that directly target thrombin or activated factor X (FXa). The two agents in the most advanced stages of development are dabigatran etexilate and rivaroxaban, which inhibit thrombin and FXa, respectively. Both are approved in the EU and Canada for venous thromboprophylaxis in patients undergoing elective hip- or knee-replacement surgery. Other agents in the early stages of development include several FXa inhibitors (apixaban, DU 176b, LY 517717, YM 150, betrixaban, eribaxaban [PD 0348292] and TAK 442) and one thrombin inhibitor (AZD 0837). With a predictable anticoagulant response and low potential for drug-drug interactions, these new agents can be given in fixed doses without coagulation monitoring. This renders them more convenient than VKAs. While the anticoagulant effect of the new thrombin and FXa inhibitors is similar, differences in the pharmacokinetic and pharmacodynamic parameters may influence their use in clinical practice. Here, we compare the pharmacokinetic and pharmacodynamic features of these new oral agents.
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- Paton, Graeme I., et al.
(författare)
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An ecotoxicity assessment of contaminated forest soils from the Kola Peninsula
- 2006
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 355:1-3, s. 106-117
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Tidskriftsartikel (refereegranskat)abstract
- Point source copper and nickel contamination emanating from smelters of the Kola Peninsula, NW Russia, has been observed since the mid-1960s. Previous studies have concentrated on the spatial distribution of heavy metals and their effects on forest ecology and indigenous mammals and birds. Soil is perceived as the major repository for the metal pollutants but there is a need to link the soil concentration of pollutants on the Kola Peninsula with biological parameters. Many standard methods currently used in soil ecotoxicology are developed and refined with artificial amendments and rarely modified for use in historically contaminated environments. In this study, forest soils were sampled along a 34 km transect from the smelter and analysed both chemically and with a range of ecologically relevant biological tests. Soil respiration, total nematode count, microbial heterotrophic numbers and minimal inhibitory concentrations to copper and nickel were carried out on bulk soil. The soil pore water was tested with bacterial and fungal bioluminescence-based biosensors. The heterotrophic numbers and their inhibitory concentration showed strong correlation with heavy metal concentrations while decreasing biosensor luminescence was related to increasing copper concentrations present in the pore waters. Overall, there were considerable impacts on some microbial parameters but other measures including respiration and nematode populations were insensitive to pollutant levels. While chemical analysis of heavy metals proved essential in defining the extent of contamination, environmentally relevant ecotoxicological tests complemented these data by demonstrating pollutant impact. Ecotoxicological approaches that study both the bulk soil and pore water may represent the key to understanding the fate of heavy metal in soils.
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