Destruction of Dopaminergic Neurons in the Midbrain by 6-Hydroxydopamine Decreases Hippocampal Cell Proliferation in Rats: Reversal by Fluoxetine

Background Non-motor symptoms (e.g., depression, anxiety, and cognitive deficits) in patients with Parkinson disease (PD) precede the onset of the motor symptoms. Although these symptoms do not respond to pharmacological dopamine replacement therapy, their precise pathological mechanisms are currently unclear. The present study was undertaken to examine whether the unilateral 6-hydroxydopamine (6-OHDA) lesion to the substantia nigra pars compacta (SNc), which represents a model of long-term dopaminergic neurotoxicity, could affect cell proliferation in the adult rat brain. Furthermore, we examined the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the selective noradrenaline reuptake inhibitor maprotiline on the reduction in cell proliferation in the subgranular zone (SGZ) by the unilateral 6-OHDA lesion. Methodology/Principal Findings A single unilateral injection of 6-OHDA into the rat SNc resulted in an almost complete loss of tyrosine hydroxylase (TH) immunoreactivity in the striatum and SNc, as well as in reductions of TH-positive cells and fibers in the ventral tegmental area (VTA). On the other hand, an injection of vehicle alone showed no overt change in TH immunoreactivity. A unilateral 6-OHDA lesion to SNc significantly decreased cell proliferation in the SGZ ipsilateral to the 6-OHDA lesion, but not in the contralateral SGZ or the subventricular zone (SVZ), of rats. Furthermore, subchronic (14 days) administration of fluoxetine (5 mg/kg/day), but not maprotiline significantly attenuated the reduction in cell proliferation in the SGZ by unilateral 6-OHDA lesion. Conclusions/Significance The present study suggests that cell proliferation in the SGZ of the dentate gyrus might be, in part, under dopaminergic control by SNc and VTA, and that subchronic administration of fluoxetine reversed the reduction in cell proliferation in the SGZ by 6-OHDA. Therefore, SSRIs such as fluoxetine might be potential therapeutic drugs for non-motor symptoms as well as motor symptoms in patients with PD, which might be associated with the reduction in cell proliferation in the SGZ

Trends identification in groundwater for the Water Framework Directive and the Groundwater Directive

In de Europese Kaderrichtlijn Water (KRW) en Grondwaterrichtlijn (GRW) is bepaald dat concentraties van verontreinigende stoffen in grondwater niet mogen stijgen. In de praktijk bleek het lastig om een dergelijke stijging vast te kunnen stellen. In twee eerder verschenen rapporten heeft het RIVM, in opdracht van het ministerie van Infrastructuur en Milieu (IenM), praktische adviezen gegeven om de technische richtlijnen uit de EU nader uit te werken. Uitgangspunt hierbij is dat bestaande informatie wordt gebruikt om trend te bepalen. Hierbij bleven vraagstukken over, waarvoor de Provincies met het RIVM in het onderliggend rapport oplossingen aanreiken. Uiteindelijk zal een protocol worden opgesteld om trends in de concentratie van stoffen, en daarmee de grondwaterkwaliteit, te kunnen bepalen. Voorbeelden van overgebleven vraagstukken zijn: wat te doen bij een tekort aan informatie of bij onvolledige tijdsreeksen, waarbij op een waarnemingspunt de concentratie van een stof door de tijd heen wordt gemeten. In zulke gevallen kan de trend worden vastgesteld op basis van een 'deskundigenoordeel'. Bij een deskundigenoordeel wordt niet met data gerekend maar beoordelen deskundigen de grondwaterkwaliteit kwalitief aan de hand van de beschikbare data. De Provincies en het RIVM hebben hiervoor een protocol opgesteld. De ouderdom van grondwater hoeft formeel niet te worden bepaald maar kan worden gebruikt om trends in het grondwatersysteem beter te begrijpen.The European Water Framework Directive (WFD) and Groundwater Directive (GRW) states that concentrations of pollutants in groundwater must not increase. In practice it proved difficult to establish such an increase. In two previously published reports, the RIVM, commissioned by the Ministry of Infrastructure and Environment (IenM), practical advice has been given for specifying the technical guidelines from the EU. Premise is that existing information has to be used to determine trend. In the underlying report answers are given by the County Councils and RIVM for issues that were not solved. Ultimately, a protocol will be formulated to establish trends in the concentration of substances and in doing so the groundwater quality. Examples of remaining issues are: what to do with a lack of information or incomplete time series, of which the concentration of a substance over time is measured at one observation point. In such cases, the trend can be established on the basis of an 'expert judgement'. An expert judgement is not based upon calculations with data but the experts evaluate the groundwater quality on the basis of qualitative assessment of the available data. For this the County Councils and RIVM have developed a protocol. Technically, the age of groundwater does not need to be determined but it can be used to improve the grasp of trends in the ground water system.Ministerie van Infrastructuur en Milie

Inventory of immunotoxic xenobiotics. Molecular and cellular backgrounds and possible influence on the immune function of the harbor seal (Phoca vitulina).

Abstract niet beschikbaarIn this report chemicals which are known to have immunotoxic properties are listed and evaluated with respect to their possible impact on the immune function of the harbour seal (Phoca vitulina).RIV

An overview of facilitators and barriers in the development of eHealth interventions for people of low socioeconomic position: A Delphi study

Objective: eHealth interventions can improve the health outcomes of people with a low socioeconomic position (SEP) by promoting healthy lifestyle behaviours. However, developing and implementing these interventions among the target group can be challenging for professionals. To facilitate the uptake of effective interventions, this study aimed to identify the barriers and facilitators anticipated or experienced by professionals in the development, reach, adherence, implementation and evaluation phases of eHealth interventions for people with a low SEP. Method: We used a Delphi method, consisting of two online questionnaires, to determine the consensus on barriers and facilitators anticipated or experienced during eHealth intervention phases and their importance. Participants provided open-ended responses in the first round and rated statements in the second round. The interquartile range was used to calculate consensus, and the (totally) agree ratings were used to assess importance. Results: Twenty-seven professionals participated in the first round, and 19 (70.4%) completed the second round. We found a consensus for 34.8% of the 46 items related to highly important rated barriers, such as the lack of involvement of low-SEP people in the development phase, lack of knowledge among professionals about reaching the target group, and lack of knowledge among lower-SEP groups about using eHealth interventions. Additionally, we identified a consensus for 80% of the 60 items related to highly important rated facilitators, such as rewarding people with a low SEP for their involvement in the development phase and connecting eHealth interventions to the everyday lives of lower-SEP groups to enhance reach. Conclusion: Our study provides valuable insights into the barriers and facilitators of developing eHealth interventions for people with a low SEP by examining current practices and offering recommendations for future improvements. Strengthening facilitators can help overcome these barriers. To achieve this, we recommend defining the roles of professionals and lower-SEP groups in each phase of eHealth intervention and disseminating this study's findings to professionals to optimize the impact of eHealth interventions for this group.Design AestheticsApplied Ergonomics and DesignMedical Delt