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| 2. |
- Karlsson, Christofer M. G., et al.
(author)
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Different gene expression responses in two Baltic Sea heterotrophic model bacteria to dinoflagellate dissolved organic matter
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Other publication (other academic/artistic)abstract
- Phytoplankton release massive amounts of dissolved organic matter (DOM) into the water column during recurring blooms in coastal waters and inland seas. The released DOM includes dissolved organic carbon, nitrogen and phosphorus, in a complex mixture of both known and unknown compounds, and is a rich nutrient source for heterotrophic bacteria. The metabolic activity of heterotrophic bacteria during and after phytoplankton blooms can hence be expected to reflect the characteristics of the released DOM. With this in mind, we wanted to investigate if bacterioplankton could be used as “living sensors” of phytoplankton DOM quantity and quality, and to trace the flow of nutrients in the ecosystem. We used transcriptional activity from Baltic Sea bacterial isolates (Polaribacter sp. BAL334 (Flavobacteriia) and Brevundimonas sp. BAL450 (Alphaproteobacteria)) exposed to DOM derived from the dinoflagellate Prorocentrum minimum in exponential and stationary growth phases respectively. We observed strong responses both in terms of physiology – bacterial abundance – and the expressed metabolic pathways – e.g. Membrane Transport, Fatty Acids, Lipids and Isoprenoids – of the populations in samples exposed to dinoflagellate DOM compared with controls. Particularly striking was the increased expression of Ton and Tol transport systems, commonly associated with uptake of complex molecules, in both isolates. Equally important were the differences in metabolic responses between the two isolates, caused by differences in gene repertoire between them, emphasizing the importance of separating the responses of different taxa in analyses of community sequence data. Differences in response to DOM sourced from exponentially and stationary growing dinoflagellates were less pronounced, although not absent, than differences between the bacterial isolates. This suggests that shifts in metabolism during the different phases of a phytoplankton bloom might be detectable in individual bacterial populations. To conclude, our work opened a door to the future use of bacterioplankton as living sensors of environmental status, particularly with respect to phytoplankton blooms.
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| 3. |
- Berglund, B E, et al.
(author)
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Sweden
- 1996
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Other publication (other academic/artistic)
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| 4. |
- Bouchene, Salim, 1984-, et al.
(author)
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A Whole-Body Physiologically Based Pharmacokinetic-Pharmacodynamic (WBPBPK-PD) Model for Colistin in Critically Ill Patients
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Other publication (other academic/artistic)abstract
- Objectives: Colistin is used as a salvage therapy for multidrug-resistant Gram-negative bacterial infections and administered as a prodrug, colistimethate sodium (CMS). Characterizing distribution of colistin at the site of infection is important to optimize bacterial killing. The aims of this analysis were (i) to apply a whole-body physiologically based pharmacokinetic (WPBPK) model structure to describe the pharmacokinetics (PK) of CMS and colistin in critically ill patients and (ii) to predict colistin concentration-time courses and bacterial killing in target tissues combining the WBPBPK model with a semi-mechanistic pharmacokinetic-pharmacodynamic (PKPD) model.Methods: 27 critically ill patients treated with colistin were included in the analysis. A WBPBPK model previously developed in rat was applied to describe CMS and colistin PK data. The model was used to predict tissue concentrations in lungs, skin, blood and kidneys to drive a semi-mechanistic PKPD model on a wild-type (ATCC 27853) or a meropenem-resistant (AUR552) clinical strain P. aeruginosa to predict bacterial killing following the original dosing regimen and by replacing the original initial dose with a loading dose of 9MU.Results: The plasma data were reasonably well described by the WBPBPK model for both CMS and colistin with a slight overprediction at the 1st occasion. High exposure was predicted in kidneys comparable to what had been predicted in previous studies, in rat and healthy subjects. Bacterial load was quickly cleared for both the ATCC 27853 and ARU552 strains in all tissues and at a higher extend in kidney tissue, for all dosing scenarios.Conclusion: The WPBPK model was able to adequately describe the PK of CMS and colistin in critically ill patients. The combination of the predicted PK profiles in tissues of interest with a PKPD model was able to predict the bactericidal effect of colistin at target sites.
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| 5. |
- Bouchene, Salim, 1984-, et al.
(author)
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Application of a whole-body physiologically based pharmacokinetic model to describe the plasma and urine disposition of colistin and colistin methanesulfonate (CMS) in healthy volunteers
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Other publication (other academic/artistic)abstract
- Objectives: The primary aim of this work was to develop a whole-body physiologically based pharmacokinetic (WBPBPK) model to describe CMS and colistin disposition in human plasma and urine. The secondary aim of this analysis was to use the WBPBPK model to predict CMS and colistin tissue distribution in typical individuals with different pathophysiological changes and receiving different dosing regimens.Methods: Twelve healthy males were included in the analysis. They received a single dose of 80 mg CMS (1 million unit) through a 1-h intravenous infusion. Venous blood was collected between 0 and 18 h post dose. Fractionated urine samples were collected between 0 and 24 h after dose. A WBPBPK model initially developed in rat was further detailed with the addition of a specific urinary tract (UT) model. The Kp values of CMS and colistin were estimated for all tissues using experimental Kp prior values from rat tissue homogenates.Results: The model adequately described CMS and colistin concentrations over time in plasma and in urine. A shared first order elimination rate constant was estimated to depict the hydrolysis of CMS in plasma and tissues. A separate hydrolysis rate constant for CMS was estimated in urine, and was lower than in plasma and tissues. A shared non-renal elimination rate constant of colistin was estimated in plasma and in tissues. CMS and colistin disposition in urine was well characterized by the UT model. The tubular reabsorption of colistin was best described by a saturable model estimating the colistin affinity constant, KM. Non-specific binding of colistin in the UT lumen was accounted for using a linear relationship.Conclusion: The WBPBPK developed in this study characterized plasma and urine PK of CMS and colistin in human well. This model was used as a new framework to predict colistin exposure in the tissues of interest under different physiological conditions. The model can be easily refined when new data are available and can be combined to PKPD models to increase the understanding of the concentration-effect relationship at target sites.
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| 6. |
- Bouchene, Salim, 1984-, et al.
(author)
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Development of an interspecies whole-body physiologically based pharmacokinetic (WBPBPK) model for colistin methanesulfonate (CMS) and colistin in five animal species and evaluation of its predictive ability in human
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Other publication (other academic/artistic)abstract
- Background and purposeColistin is a last-line antibiotic administered as the prodrug colistin methanesulfonate (CMS) for the treatment of multidrug resistant Gram-negative bacterial infections. Whole-body physiologically based pharmacokinetic (WBPBPK) models are valuable tools to understand and characterize drug disposition, predict tissue distribution and interpret exposure-response relationship. The aim of this work was to develop a WBPBPK model for colistin and CMS in five animal species and evaluate the utility of the model for predicting colistin and CMS disposition in human.MethodsA nonlinear mixed-effects WBPBPK model previously developed in rats was extended to describe CMS and colistin plasma data of animals from 5 different species (40 mice, 6 rats, 3 rabbits, 3 baboons and 2 pigs) that had received single doses of CMS. CMS renal clearance and hydrolysis to colistin were allometrically scaled based on glomerular filtration rate (GFR) and tissue volumes, respectively. For the non-renal colistin clearance, three scaling models were evaluated: volume based allometric scaling, volume and maximum lifespan potential (MLP) based allometric scaling, and estimation of specie-specific parameters. Tissue concentrations were predicted for all species. The WBPBPK model was then used to predict human plasma concentrations, which were compared to observed human plasma PK data extracted from literature.ResultsThe description of the plasma PK of CMS and colistin in mice, rats, rabbits, baboons and pigs was satisfactory. The volume and MLP based allometric scaling of the non-renal clearance of colistin was best at characterizing colistin concentration-time course, even if a misprediction remained in pigs. In human however, allometric scaling without MLP was closest to the observed data, with satisfactory prediction of the CMS plasma profiles and a slight overprediction of colistin plasma PK profiles.ConclusionsInterspecies WBPBPK models were developed to describe the disposition of CMS and colistin across five animal species and human plasma concentrations of CMS and colistin were predicted in the right ranges.
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| 7. |
- Ericson, Y, et al.
(author)
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Faktablad från Integrerad kustfiskövervakning: Fjällbacka (Västerhavet) 1989-2015
- 2016
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In: Faktablad 2016 från Inst för Akvatiska resurser, SLU. ; :2016:1
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Other publication (other academic/artistic)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Fjällbacka-området 1989-2015. Övervakningen visar att situationen för tånglake i Fjällbacka är ansträngd. En återhämtning kan dock skönjas de allra sista åren. Tidigare vikande fångster och en försämring av tånglakens hälsotillstånd samt yngelstatus antyder att arten påverkas negativt av omgivningsfaktorer såsom den ökande vattentemperaturen, syrenivåer och exponering för kemikalier.
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| 8. |
- Ericson, Y, et al.
(author)
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Faktablad från Integrerad kustfiskövervakning: Kvädöfjärden (Egentliga Östersjön) 1989-2015.
- 2016
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In: Faktablad 2016 från Inst för Akvatiska Resurser, SLU. ; :2016:3
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Other publication (other academic/artistic)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Kvädöfjärden under tidsperioden 1989-2015. Kustfiskövervakningen visar på minskande karpfiskbestånd, minskad totalfångst av fisk och ett påverkat hälsotillstånd hos abborre och tånglake, samtidigt som de flesta analyserade miljögifter visar nedåtgående trender eller oförändrade halter.
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| 9. |
- Ericson, Y, et al.
(author)
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Faktablad från Integrerad kustfiskövervakning: Torhamn (södra Egentliga Östersjön) 2002-2015
- 2016
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In: Faktablad 2016 från Inst för Akvatiska resurser, SLU. ; :2016:4
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Other publication (other academic/artistic)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Torhamnsområdet under tidsperioden 2002-2015. Resultaten från tretton års undersökningar visar en alltmer tydlig påverkan på hälsotillståndet hos abborre liknande den som observeras hos abborre och tånglake i andra kustreferensområden. Denna tydliga och successiva påverkan som ses på abborrens hälsa på individnivå har ännu inte resulterat i några påtagliga förändringar på bestånds- eller samhällsnivå.
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