Individual differences in the sensitivity to serotonergic drugs: a pharmacobehavioural approach using rats selected on the basis of their response to novelty

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Barometer Maatschappelijk Vastgoed 2011

Het doel van dit onderzoek “Barometer Maatschappelijk Vastgoed 2011” is het transparanter en inzichtelijker maken van maatschappelijk vastgoed bij Nederlandse gemeenten. Naast dit doel is er ook een hoger doel te benoemen, namelijk de respons te verhogen van het onderzoek Barometer Maatschappelijk Vastgoed 2011 ten opzichte van de voorgaande vier onderzoek jaren. Het onderzoek van dit jaar heeft geleid tot een trendbreuk in het onderzoek. Doel was om dit jaar alle gemeenten in Nederland te enquêteren, en dieper op het maatschappelijk vastgoed in te gaan. Wat bleek; een landelijke enquête met een dusdanig gedetailleerd onderzoek is niet uitvoerbaar. Aan de hand hiervan is de probleemstelling opgesteld. De probleemstelling van dit rapport luidt; ‘Wat heeft geleid tot een trendbreuk in de onderzoeksresultaten van de Barometer Maatschappelijk Vastgoed 2011?’ Aan de hand van de probleemstelling zijn twee deelvragen opgesteld; - Aan welke voorwaarden moet het meetinstrument voor de Barometer Maatschappelijk Vastgoed 2011 voldoen voor het maximaliseren/ verhogen van de respons? - Hoe denken gemeenten over het belang van het efficiënt beheren van maatschappelijk vastgoed? Studentonderzoek in het kader van het thema Leefomgevin

Individual differences in the sensitivity to serotonergic drugs: a pharmacobehavioural approach using rats selected on the basis of their response to novelty. Psychopharmacology 205

Abstract Rationale The mechanisms underlying individual differences in the response to serotonergic drugs are poorly understood. Rat studies may contribute to our knowledge of the neuronal substrates that underlie these individual differences. Objectives A pharmacobehavioural study was performed to assess individual differences in the sensitivity to serotonergic drugs in rats that were selected based on their response to a novel environment. Methods Low responders (LR) and high responders (HR) to novelty rats were tested on the elevated T-maze following systemic injections of increasing doses of various serotonergic agents. The duration of avoidance of the open arms was scored for five trials. Results The duration of avoidance behaviour was larger in saline-treated LR rats compared to saline-treated HR rats. The 5-HT1A agonist 8-OH-DPAT and the 5-HT2 agonists mCPP and DOI decreased the duration of avoidance behaviour in LR rats, but increased it in HR rats. The 5-HT3 agonist SR57227A and the 5-HT releaser/reuptake inhibitor d-fenfluramine increased the duration of avoidance behaviour in both types of rat. However, higher doses of SR57227A were required to alter avoidance behaviour in HR than in LR rats. The onset of the effects of SR57227A, d-fenfluramine and WAY100635 was faster in LR than in HR rats. The described effects were receptor specific. A model explaining the data is presented. Conclusions These data demonstrate that LR and HR rats differ in their sensitivity to serotonergic drugs that act at 5-HT3, 5-HT2 and 5-HT1A receptors. The implications of these individual differences for individual-specific treatment of substance abuse are briefly discussed

Oxidative potential of particulate matter collected at sites with different source characteristics

Background: The oxidative potential (OP) of particulate matter (PM) has been proposed as a more health relevant metric than PM mass. Different assays exist for measuring OP and little is known about how the different assays compare. Aim: To assess the OP of PM collected at different site types and to evaluate differences between locations, size fractions and correlation with PM mass and PM composition for different measurement methods for OP. Methods: PM2.5 and PM10 was sampled at 5 sites: an underground station, a farm, 2 traffic sites and an urban background site. Three a-cellular assays; dithiothreitol (OPDTT), electron spin resonance (OPESR) and ascorbate depletion (OPAA) were used to characterize the OP of PM. Results: The highest OP was observed at the underground, where OP of PM10 was 30 (OPDTT) to >600 (OPESR) times higher compared to the urban background when expressed as OP/m(3) and 2-40 times when expressed as OP/mu g. For the outdoor sites, samples from the farm showed significantly lower OPESR and OPAA, whereas samples from the continuous traffic site showed the highest OP for all assays. Contrasts in OP between sites were generally larger than for PM mass and were lower for OPDTT compared to OPESR and OPAA. Furthermore, OPDTT/mu g was significantly higher in PM2.5 compared to PM10, whereas the reverse was the case for OPESR. OPESR and OPAA were highly correlated with traffic-related PM components (i.e. EC, Fe, Cu, PAHs), whereas OPDTT showed the highest correlation with PM mass and OC. Conclusions: Contrasts in OP between sites, differences in size fractions and correlation with PM composition depended on the specific OP assay used, with OPESR and OPAA showing the most similar results. This suggests that either OPESR or OPAA and OPDTT can complement each other in providing information regarding the oxidative properties of PM, which can subsequently be used to study its health effects. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved

Air pollution exposure affects circulating white blood cell counts in healthy subjects:the role of particle composition, oxidative potential and gaseous pollutants - the RAPTES project.

Studies have linked air pollution exposure to cardiovascular health effects, but it is not clear which components drive these effects. We examined the associations between air pollution exposure and circulating white blood cell (WBC) counts in humans. To investigate independent contributions of particulate matter (PM) characteristics, we exposed 31 healthy volunteers at five locations with high contrast and reduced correlations amongst pollutant components: two traffic sites, an underground train station, a farm and an urban background site. Each volunteer visited at least three sites and was exposed for 5 h with intermittent exercise. Exposure measurements on-site included PM mass and number concentration, oxidative potential (OP), elemental- and organic carbon, metals, O-3 and NO2. Total and differential WBC counts were performed on blood collected before and 2 and 18 h post-exposure (PE). Changes in total WBC counts (2 and 18 h PE), number of neutrophils (2 h PE) and monocytes (18 h PE) were positively associated with PM characteristics that were high at the underground site. These time-dependent changes reflect an inflammatory response, but the characteristic driving this effect could not be isolated. Negative associations were observed for NO2 with lymphocytes and eosinophils. These associations were robust and did not change after adjustment for a large suite of PM characteristics, suggesting an independent effect of NO2. We conclude that short-term air pollution exposure at real-world locations can induce changes in WBC counts in healthy subjects. Future studies should indicate if air pollution exposure-induced changes in blood cell counts results in adverse cardiovascular effects in susceptible individuals

Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers

INTRODUCTION: We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects. METHODS: We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm and an urban background site. Each volunteer visited at least three sites. We conducted health measurements before exposure, 2 h after exposure and the next morning. We measured air pollution on site and characterised the OP of PM2.5 and PM10 using three a-cellular assays; dithiotreitol (OP(DTT)), electron spin resonance (OP(ESR)) and ascorbic acid depletion (OP(AA)). RESULTS: In single-pollutant models, all measures of OP were significantly associated with increases in fractional exhaled nitric oxide and increases in interleukin-6 in nasal lavage 2 h after exposure. These OP associations remained significant after adjustment for co-pollutants when only the four outdoor sites were included, but lost significance when measurements at the underground site were included. Other health end points including lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. CONCLUSIONS: We found significant associations between three a-cellular measures of OP of PM and markers of airway and nasal inflammation. However, consistency of these effects in two-pollutant models depended on how measurements at the underground site were considered. Lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Our study, therefore, provides limited support for a role of OP in predicting acute health effects of PM in healthy young adults