| 1. |
- Kip, A E, et al.
(författare)
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Quantification of miltefosine in peripheral blood mononuclear cells by high-performance liquid chromatography-tandem mass spectrometry.
- 2015
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 998-999, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- Phagocytes, the physiological compartment in which Leishmania parasites reside, are the main site of action of the drug miltefosine, but the intracellular pharmacokinetics of miltefosine remain unexplored. We developed a bioanalytical method to quantify miltefosine in human peripheral blood mononuclear cells (PBMCs), expanding from an existing high performance liquid chromatography-tandem mass spectrometry method for the quantification of miltefosine in plasma. The method introduced deuterated miltefosine as an internal standard. Miltefosine was extracted from PBMC pellets by addition of 62.5% methanol. Supernatant was collected, evaporated and reconstituted in plasma. Chromatographic separation was performed on a reversed phase C18 column and detection with a triple-quadrupole mass spectrometer. Miltefosine was quantified using plasma calibration standards ranging from 4 to 1000ng/mL. This method was validated with respect to its PBMC matrix effect, selectivity, recovery and stability. No matrix effect could be observed from the PBMC content (ranging from 0.17 to 26.3×10(6)PBMCs) reconstituted in plasma, as quality control samples were within 3.0% of the nominal concentration (precision less than 7.7%). At the lower limit of quantitation of 4 ng/mL plasma, corresponding to 0.12ng/10(6) PBMCs in a typical clinical sample, measured concentrations were within 8.6% of the nominal value. Recovery showed to be reproducible as adding additional pre-treatment steps did not increase the recovery with more than 9%. This method was successfully applied to measure intracellular miltefosine concentrations in PBMC samples from six cutaneous leishmaniasis patients up to one month post-treatment.
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| 2. |
- Kip, A E, et al.
(författare)
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Validation and clinical evaluation of a novel method to measure miltefosine in leishmaniasis patients using dried blood spot sample collection
- 2016
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 60:4, s. 2081-2089
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Tidskriftsartikel (refereegranskat)abstract
- To facilitate future pharmacokinetic studies of combination treatments against leishmaniasis in remote endemic regions, a simple and cheap sampling methodology was required for miltefosine quantification. The aim of this study was to validate a liquid chromatography-tandem mass spectrometry method to quantify miltefosine in dried blood spots (DBS) and to validate its use in Ethiopian visceral leishmaniasis (VL) patients. Since hematocrit (Ht) values are typically severely decreased in VL patients, regressing to normal during treatment, the method was evaluated over a range of clinically relevant Ht values.Miltefosine was extracted from DBS using a simple pre-treatment method with methanol, resulting in >97% recovery. The method was validated over a calibration range of 10-2,000 ng/mL and accuracy and precision were within ±11.2% and ≤7.0% (≤19.1% at LLOQ), respectively. The method was accurate and precise for blood spot volumes between 10-30 μL and for an Ht of 20-35%, though a linear effect of Ht on miltefosine quantification was observed in the bioanalytical validation. DBS samples were stable for at least 162 days at 37°C.Clinical validation of the method using paired DBS and plasma samples from 16 VL patients showed a median observed DBS:plasma miltefosine concentration ratio of 0.99, with good correlation (Pearson's r=0.946). Correcting for patient-specific Ht did not further improve the concordance between the sampling methods.This successfully validated method to quantify miltefosine in DBS was demonstrated to be a valid and practical alternative to venous blood sampling which can be applied in future miltefosine pharmacokinetic studies in leishmaniasis patients, without Ht-correction.
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| 3. |
- Lewandowska, A. M., et al.
(författare)
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The influence of balanced and imbalanced resource supply on biodiversity-functioning relationship across ecosystems
- 2016
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Ingår i: Philosophical Transactions of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1694
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies show that increasing species richness leads to higher ecosystem productivity. This effect is often attributed to more efficient portioning of multiple resources in communities with higher numbers of competing species, indicating the role of resource supply and stoichiometry for biodiversity ecosystern functioning relationships. Here, we merged theory on ecological stoichiometry with a framework of biodiversity ecosystem functioning to understand how resource use transfers into primary production. We applied a structural equation model to define patterns of diversity productivity relationships with respect to available resources. Meta-analysis was used to summarize the findings across ecosystem types ranging from aquatic ecosystems to grasslands and forests. As hypothesized, resource supply increased realized productivity and richness, but we found significant differences between ecosystems and study types. Increased richness was associated with increased productivity, although this effect was not seen in experiments. More even communities had lower productivity, indicating that biomass production is often maintained by a few dominant species, and reduced dominance generally reduced ecosystem productivity. This synthesis, which integrates observational and experimental studies in a variety of ecosystems and geographical regions, exposes common pattems and differences in biodiversity functioning relationships, and increases the mechanistic understanding of changes in ecosystems productivity.
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| 8. |
- Dorlo, Thomas P C, et al.
(författare)
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Development and validation of a quantitative assay for the measurement of miltefosine in human plasma by liquid chromatography-tandem mass spectrometry.
- 2008
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 865:1-2, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of miltefosine is presented. A 250 microL human EDTA plasma aliquot was spiked with miltefosine and extracted by a solid-phase extraction method. Separation was performed on a Gemini C18 column (150 mm x 2.0 mm I.D., 5 microm) using an alkaline eluent. Detection was performed by positive ion electrospray ionization followed by triple-quadrupole mass spectrometry. The assay has been validated for miltefosine from 4 to 2000 ng/mL using 250 microL human EDTA plasma samples. Results from the validation demonstrate that miltefosine can be accurately and precisely quantified in human plasma. At the lowest level, the intra-assay precision was lower than 10.7%, the inter-assay precision was 10.6% and accuracies were between 95.1 and 109%. This assay is successfully used in a clinical pharmacokinetic study with miltefosine.
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| 9. |
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| 11. |
- Gamfeldt, Lars, 1975, et al.
(författare)
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Biodiversity effects on aquatic ecosystem functioning - maturation of a new paradigm
- 2008
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Ingår i: International Review of Hydrobiology. ; 93:4-5, s. 550-564
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Tidskriftsartikel (refereegranskat)abstract
- Starting with the publication of some influential studies in the early 1990’s, the topic of biodiversity and ecosystem functioning has emerged as a major field within ecological research. Within this framework, the diversity of genotypes, species and functional groups are considered as explanatory variables of ecosystem functions rather than response variables of factors such as productivity and disturbance. Biodiversity-ecosystem functioning research has received considerable attention, and new publications are emerging at a high pace. Both the validity of experimental approaches and the way the results may be extrapolated to natural systems have, however, been widely discussed. The width of the debate regarding whether or not biodiversity is important for ecosystem functioning have encouraged many scientists to refine both experiments and theory, as well as develop novel methods to analyse the relationship between diversity and functioning. Aquatic ecologists have contributed greatly to the evolution of ideas and concepts within the field. In this review, we discuss how the paradigm that biodiversity is an important factor for the functioning of aquatic ecosystems is currently maturing with more realistic studies embracing both new and innovative approaches. We also suggest fruitful areas for future research.
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| 14. |
- Gamfeldt, Lars, 1975, et al.
(författare)
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Species richness changes across two trophic levels simultaneously affect prey and consumer biomass
- 2005
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 8:7, s. 696-703
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Tidskriftsartikel (refereegranskat)abstract
- Increasing species richness of primary producers or consumers is proposed to increase primary and secondary production; however, the consequences of biodiversity change across trophic levels has been poorly investigated. We used a controlled marine microbial system to investigate the effects of simultaneous changes in biodiversity of consumer and prey species. Consumer (ciliates) and prey (algae) richness and identity were manipulated independently in a complete factorial design. The results showed clear biodiversity effects of both consumers and prey, within and across trophic levels. We found reduced prey and increased consumer biomass with increased consumer richness, with the most diverse prey assemblage supporting the highest biomass of consumers at the highest richness of consumers. Increasing prey richness did not increase resistance to consumption when consumers were present. Instead, our results indicated enhanced energy transfer with simultaneous increasing richness of consumers and prey.
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| 15. |
- Gruner, D. S., et al.
(författare)
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Effects of experimental warming on biodiversity depend on ecosystem type and local species composition
- 2017
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Ingår i: Oikos. - : Wiley. - 0030-1299. ; 126:1, s. 8-17
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Tidskriftsartikel (refereegranskat)abstract
- Climatic warming is a primary driver of change in ecosystems worldwide. Here, we synthesize responses of species richness and evenness from 187 experimental warming studies in a quantitative meta-analysis. We asked 1) whether effects of warming on diversity were detectable and consistent across terrestrial, freshwater and marine ecosystems, 2) if effects on diversity correlated with intensity, duration, and experimental unit size of temperature change manipulations, and 3) whether these experimental effects on diversity interacted with ecosystem types. Using multilevel mixed linear models and model averaging, we also tested the relative importance of variables that described uncontrolled environmental variation and attributes of experimental units. Overall, experimental warming reduced richness across ecosystems (mean log-response ratio = -0.091, 95% bootstrapped CI: -0.13, -0.05) representing an 8.9% decline relative to ambient temperature treatments. Richness did not change in response to warming in freshwater systems, but was more strongly negative in terrestrial (-11.8%) and marine (-10.5%) experiments. In contrast, warming impacts on evenness were neutral overall and in aquatic systems, but weakly negative on land (7.6%). Intensity and duration of experimental warming did not explain variation in diversity responses, but negative effects on richness were stronger in smaller experimental units, particularly in marine systems. Model-averaged parameter estimation confirmed these main effects while accounting for variation in latitude, ambient temperature at the sites of manipulations, venue (field versus lab), community trophic type, and whether experiments were open or closed to colonization. These analyses synthesize extensive experimental evidence showing declines in local richness with increased temperature, particularly in terrestrial and marine communities. However, the more variable effects of warming on evenness were better explained by the random effect of site identity, suggesting that effects on species' relative abundances were contingent on local species composition.
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| 20. |
- Saari, Ulla A., et al.
(författare)
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How consumers’ respect for nature and environmental self-assets influence their car brand experiences
- 2020
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Ingår i: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 261
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Tidskriftsartikel (refereegranskat)abstract
- This paper provides a novel perspective on sustainability research by exploring how two pro-environmental characteristics of consumers – respect for nature and environmental self-assets – influence their brand experiences. The study uses survey data collected on a car brand that incorporated eco-friendly advances. The results show that respect for nature has an impact on how respondents experience the eco-friendliness of brands and that eco-friendly brand experiences in turn influence general brand experiences. The findings also suggest that the effects of the two pro-environmental characteristics depend on the education level of the consumer: eco-friendly brand experiences of highly educated consumers are affected by their respect for nature, whereas those of consumers with lower education levels are affected by environmental self-assets.
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| 21. |
- Urrutia-Cordero, P., et al.
(författare)
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SITES AquaNet: An open infrastructure for mesocosm experiments with high frequency sensor monitoring across lakes
- 2021
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Ingår i: Limnology and Oceanography-Methods. - : Wiley. - 1541-5856. ; 19:6, s. 385-400
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Tidskriftsartikel (refereegranskat)abstract
- For aquatic scientists mesocosm experiments are important tools for hypothesis testing as they offer a compromise between experimental control and realism. Here we present a new mesocosm infrastructure-SITES AquaNET-located in five lakes connected to field stations in Sweden that cover a similar to 760 km latitudinal gradient. SITES AquaNet overcomes major hindrances in aquatic experimental research through: (i) openness to the scientific community, (ii) the potential to implement coordinated experiments across sites and time, and (iii) high-frequency measurements (temperature, photosynthetic photon flux density, turbidity and dissolved oxygen, chlorophyll a and phycocyanin concentrations) with an autonomous sensor system. Moreover, the infrastructure provides operational guidance and sensor expertise from technical staff, and connections to a multi-layered monitoring programme ("SITES Water") for each lake. This enables ecological observations from whole lake ecosystems to be compared with experimental studies aiming at disentangling major drivers and mechanisms underlying observed changes. Here we describe the technical properties of the infrastructure along with possibilities for experimental manipulations to tackle pressing issues in aquatic ecology and global change science. As a proof of concept, we also present a first mesocosm experiment across all five field sites with a cross-factorial design to evaluate responses of the sensor measurements to press/bottom-up (constant light reduction) and pulse/top-down (temporary fish predation) disturbances. This demonstrates the suitability of the infrastructure and autonomous sensor system to host modularized experiments and exemplifies the power and advantages of the approach to integrate a network of mecsocosm facilities with manageable costs across large geographic areas.
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| 22. |
- Verhagen, Linda A W, et al.
(författare)
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Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity.
- 2011
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Ingår i: European neuropsychopharmacology. - : Elsevier BV. - 1873-7862 .- 0924-977X. ; 21:5, s. 384-392
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Tidskriftsartikel (refereegranskat)abstract
- Using the rodent activity-based anorexia (ABA) model that mimics clinical features of anorexia nervosa that include food restriction-induced hyperlocomotion, we found that plasma ghrelin levels are highly associated with food anticipatory behaviour, measured by running wheel activity in rats. Furthermore, we showed that ghrelin receptor (GHS-R1A) knockout mice do not anticipate food when exposed to the ABA model, unlike their wild type littermate controls. Likewise, food anticipatory activity in the ABA model was suppressed by a GHS-R1A antagonist administered either by acute central (ICV) injection to rats or by chronic peripheral treatment to mice. Interestingly, the GHS-R1A antagonist did not alter food intake in any of these models. Therefore, we hypothesize that suppression of the central ghrelin signaling system via GHS-R1A provides an interesting therapeutic target to treat hyperactivity in patients suffering from anorexia nervosa.
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