Biomedical subjects

R Smolders

Publications and source records attributed to R Smolders.

4 recordsLinked to original sources

PubMed2004

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization.

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels.

Adaptation, Physiological↗

PubMed2004

In situ and laboratory bioassays to evaluate the impact of effluent discharges on receiving aquatic ecosystems.

Effluents are a main source of direct and often continuous input of pollutants into aquatic ecosystems with long-term implications on ecosystem functioning. Therefore, the study of the effects of effluent exposure on organisms, populations or communities within the framework of impact assessment has a high ecological relevance. The aim of this study was to assess the toxicological impact of two effluents, one household wastewater treatment effluent (Effluent 1) and one industrial effluent (Effluent 2), on the receiving aquatic ecosystem using two test species under both in situ and laboratory conditions. Zebra mussel (Dreissena polymorpha) and common carp (Cyprinus carpio) were exposed under laboratory conditions in an online monitoring flow-through system (receiving different concentrations of Effluent 2) and under in situ conditions along the pollution gradient established by these two effluent discharges. Bioassays focussed on growth and condition related endpoints (i.e. condition, growth, lipid budget), since these are key functional processes within organisms and populations. Under laboratory conditions, increasing concentrations of the industrial effluent (Effluent 2) had a negative effect on both zebra mussel and carp energy reserves and condition. Under in situ conditions, the same negative impact of Effluent 2 was observed for zebra mussels, while Effluent 1 had no apparent effect on exposed zebra mussels. Carp growth and condition, on the other hand, were significantly increased at the discharge sites of both effluents when compared to the reference site, probably due to differences in food availability. The results indicate that a combination of in situ and laboratory exposures can illustrate how ecological processes influence bioassay studies. The incorporation of indirect, ecological effects, like changes in food availability, provides considerable benefit in understanding and predicting effects of effluents on selected species under realistic exposure conditions.

Animals↗

PubMed2004

An ecologically relevant exposure assessment for a polluted river using an integrated multivariate PLS approach.

A case study is presented where an integrated, ecologically relevant exposure assessment is presented for a polluted lowland river. Using partial least squares regression of latent structures (PLS), an analysis of the impact of two effluents on physico-chemical water quality measures, macroinvertebrate and diatom communities, and in situ bioassay responses with four different test species are combined into an integrative exposure assessment. Bioassays focussed on growth and condition related endpoints, because they are key functional processes of organisms and populations. Integrating these multiple lines of evidence, we were able to discriminate among the impact of both effluents, link changes in physico-chemical water quality with bioassay endpoints and ecological quality of the ecosystem, and address the importance of integrating all information into one exposure assessment framework. The bioassays under field conditions indicated that most endpoints measured are a reflection of ecological effects rather than pollution related effects, or at least a combination of both ecological and toxicological effects. Factors such as food availability clearly influenced the outcome of in situ bioassays and ecological information was essential to explain observed discrepancies when trying to extrapolate bioassay results from the laboratory to the field.

Animals↗

PubMed2001

Active efflux of the 5-HT(1A) receptor agonist flesinoxan via P-glycoprotein at the blood-brain barrier.

The role of P-glycoprotein on the efflux of the 5-HT(1A) receptor agonist flesinoxan across the blood-brain barrier in vivo and in vitro was investigated. In vitro, the transport ratios (representing polarized transport) of flesinoxan (10 microg/ml) were 4.2 in the MDR1-transfected LLC-PK1 cell line, which could be inhibited by the Pgp modulators SDZ-PSC 833 and LY 335979 and 1.1 in the wild-type LLC-PK1 cell line after 4 h. Flesinoxan concentrations lower than 33 microg/ml were actively transported by Pgp, while at higher concentrations Pgp became saturated and transport in the MDR1-transfected cell line was comparable with the wild-type cell line. In the in vitro BBB co-culture model the transport ratio was 2.0 and was decreased to 1.0 in the presence of Pgp modulators. In vivo, the accumulation of flesinoxan in the brain at 3 h was much higher in the mdr1a(-/-) mice compared to mdr1a(+/+) mice (ratio 12.6 and 27.0 at dose levels of 3 mg/kg and 10 mg/kg respectively). In conclusion, both in vivo as well as in vitro results have demonstrated that Pgp is a limiting factor for the transport of the 5-HT(1A) receptor agonist flesinoxan into the CNS. This should be considered when its application in therapy is combined with other Pgp substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗