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Sökning: WFRF:(Förlin Lars 1950 ) > Fick Jerker

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1.
  • Cuklev, Filip, et al. (författare)
  • Diclofenac in fish: Blood plasma levels similar to human therapeutic levels affect global hepatic gene expression.
  • 2011
  • Ingår i: Environmental toxicology and chemistry / SETAC. - 1552-8618. ; 30:9, s. 2126-34
  • Tidskriftsartikel (refereegranskat)abstract
    • Diclofenac is a non-steroidal anti-inflammatory drug frequently found in the aquatic environment. Previous studies have reported histological changes in the liver, kidney and gills of fish at concentrations similar to those measured in treated sewage effluents (approximately 1 µg/L). Analyses or predictions of blood plasma levels in fish allow a direct comparison with human therapeutic plasma levels, and may therefore be used to indicate a risk for pharmacological effects in fish. To relate internal exposure to a pharmacological interaction we investigated global hepatic gene expression together with bioconcentration in blood plasma and liver of rainbow trout (Oncorhynchus mykiss) exposed to waterborne diclofenac. At the highest exposure concentration (81.5 µg/L) the fish plasma concentration reached approximately 88% of the human therapeutic levels (C(max) ) after two weeks. Using an oligonucleotide microarray followed by quantitative PCR we found extensive effects on hepatic gene expression at this concentration, and some genes were found to be regulated down to the lowest concentration tested (1.6 µg/L) corresponding to approximately 1.5% of the human C(max) . Thus, at concentrations detected in European surface waters, diclofenac can affect the expression of multiple genes in exposed fish. Functional analysis of differentially expressed genes revealed effects on biological processes such as inflammation and immune response, in agreement with the mode of action of diclofenac in mammals. In contrast to some previously reported results, the bioconcentration factor was found to be stable (4.02 ± 0.75 for blood plasma and 2.54 ± 0.36 for liver) regardless of the water concentration. Environ. Toxicol. Chem. © 2011 SETAC.
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  • Larsson, D. G. Joakim, 1969-, et al. (författare)
  • Release of active pharmaceutical ingredients from Indian bulk drug manufacture – environmental fate and effects on antibiotic resistance development, microbial ecosystems and vertebrate physiology
  • 2008
  • Ingår i: 2008 Society of Environmental Toxicology and Chemistry, November 16-20, Tampa, USA.
  • Konferensbidrag (refereegranskat)abstract
    • Last year, we published a paper showing extraordinary high levels of several drugs in treated effluent from a plant receiving process water from about 90 bulk drug manufacturers from the Hyderabad region in India. Particularly, the levels of various fluoroquinolones (up to 31 mg/L) called for more information on the potential development of antibiotic resistance of exposed bacteria, as well as potential ecological effects on microbial ecosystems. In this study we will present the first characterization of 93 strains of bacteria sampled inside the treatment facility for their sensitivity/resistance to 39 different antibiotics. Furthermore, controlled exposure experiments suggest that the treated effluent affects the functional structure of natural freshwater microbial communities at a dilution of 1:1000. Short to medium-term exposure experiments with frogs and fish demonstrate sublethal effects of the treated effluent at similar dilutions, suggesting that expected environmental effects are not restricted to disturbed microorganism communities. Data on the fate of different pharmaceuticals in a gradient up and downstream from the treatment facility will be presented, as well as levels in drinking water wells in seven nearby villages, showing a transport of drugs via the groundwater. We conclude that the environmental impact of drug production in the Hyderabad region is of great environmental concern. We will also present summary data on the origin of active substances present in pharmaceutical products on the Swedish market, implying an international responsibility for improving the environmental pollution situation related to bulk drug production in India.
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