Staat van de ambtelijke dienst 2015 De overheid in tijden van verandering

bookHervorming Sociale Regelgevin

The role of P-glycoprotein in CNS antihistamine effects

RATIONALE: P-glycoprotein (P-gp) is a drug efflux pump expressed, amongst others, on the luminal surface of the cerebral endothelial cells forming the blood-brain barrier. Studies in rodents have demonstrated that antihistamines that are substrates of the P-gp transporter display no or minor central nervous system (CNS) effects as compared to antihistamines that are not P-gp transporter substrates. OBJECTIVES: The present study explored whether P-gp contributes in similar ways to the occurrence of sedative effects of antihistamines in humans. METHODS: An fMRI study was conducted according to a double-blind, randomized, placebo-controlled, cross-over design in 13 healthy volunteers. Participants received cetirizine 15 mg (an antihistamine), verapamil 120 mg (a P-gp blocker), a combination of cetirizine + verapamil, and a placebo. Brain activity was assessed while conducting the attention network test (ANT) in a 3T magnetic resonance scanner. The ANT measures three independent attention domains: i.e., alerting, orienting, and executive attention. It was expected that the combined treatment of cetirizine with verapamil would prevent efflux of cetirizine from the CNS, thus increasing attentional impairment, as compared to cetirizine administered alone. RESULTS: The present study provides evidence that the P-gp transporter is involved in central antihistamine effects in humans. Participants were less alert during the combined treatment of cetirizine and verapamil as indicated by longer reaction times and decreased blood oxygen level-dependent response in the right superior temporal gyrus. CONCLUSION: It is concluded that the affinity for the P-gp transporter may contribute to the lower incidence of CNS side effects of certain antihistamines

Contrast Material-induced Nephropathy in the Era of Hydration

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Species richness of the genus Molgolaimus (Nematoda) from local- to ocean-scale along continental slopes

This study investigated the distribution of Molgolaimus species (Nematoda) at different hierarchical spatial scales and observed the turnover of species along bathymetrical transects and among transects in two separate geographical regions. Samples from six transects (200-2000 m) from the Southern Oceans (SO) and four bathymetric transects (50-2000 m) from the Western Indian Ocean (WIO) were compared. Of the 30 species recorded, only one was common to both regions. WIO had higher local species richness than the SO. In both regions, the local scale was the greatest contributor to the total species richness. In the SO, there was no difference between species turnover at the different spatial scales, however, in the WIO, the turnover along bathymetrical transects was higher than among separated transects. For the particular genus studied, the evidence suggests that the study area in WIO has more widespread species and was better sampled, while the SO has many restricted species and it is most probably characterized by different biogeographical provinces. At the ocean scale (i.e. WIO versus SO), evolutionary histories may have strongly influenced nematodes species composition, while at local and regional scales, ecological processes are probably promoting species co-existence and speciation. The high co-existence of certain species at local scale is partially explained by species preference for different sediment layers

Plant macrofossils and pollen in goat/sheep faeces from the Neolithic lake-shore settlement Arbon Bleiche 3, Switzerland

Over 300 goat/sheep faeces from the Neolithic lake-shore settlement of Arbon Bleiche 3 (3384-3370 bc) were analysed for macrofossils and 22 of them for pollen. Two main types of fodder could be detected, which were both consumed in winter. The more frequent type is characterized by remains of blackberry (Rubus fruticosus s. l.) probably showing the use of pasture in the near surroundings of the settlement. The second type is dominated by leaf fragments of silver fir (Abies alba) and by pollen and anthers of early-flowering shrubs such as hazel (Corylus avellana) and alder (Alnus sp.), pointing in the latter cases to additional foddering of twigs to livestock inside the settlement in times of shortage. Comparison with other Neolithic sites of Switzerland reveals differences that may indicate local adaptations in the keeping of goats or sheep