2 resultados para Stella

em Helda - Digital Repository of University of Helsinki


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"Fifty-six teachers, from four European countries, were interviewed to ascertain their attitudes to and beliefs about the Collaborative Learning Environments (CLEs) which were designed under the Innovative Technologies for Collaborative Learning Project. Their responses were analysed using categories based on a model from cultural-historical activity theory [Engestrom, Y. (1987). Learning by expanding.- An activity-theoretical approach to developmental research. Helsinki: Orienta-Konsultit; Engestrom, Y., Engestrom, R., & Suntio, A. (2002). Can a school community learn to master its own future? An activity-theoretical study of expansive learning among middle school teachers. In G. Wells & G. Claxton (Eds.), Learning for life in the 21st century. Oxford: Blackwell Publishers]. The teachers were positive about CLEs and their possible role in initiating pedagogical innovation and enhancing personal professional development. This positive perception held across cultures and national boundaries. Teachers were aware of the fact that demanding planning was needed for successful implementations of CLEs. However, the specific strategies through which the teachers can guide students' inquiries in CLEs and the assessment of new competencies that may characterize student performance in the CLEs were poorly represented in the teachers' reflections on CLEs. The attitudes and beliefs of the teachers from separate countries had many similarities, but there were also some clear differences, which are discussed in the article. (c) 2005 Elsevier Ltd. All rights reserved."

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The blood-brain barrier (BBB) is a unique barrier that strictly regulates the entry of endogenous substrates and xenobiotics into the brain. This is due to its tight junctions and the array of transporters and metabolic enzymes that are expressed. The determination of brain concentrations in vivo is difficult, laborious and expensive which means that there is interest in developing predictive tools of brain distribution. Predicting brain concentrations is important even in early drug development to ensure efficacy of central nervous system (CNS) targeted drugs and safety of non-CNS drugs. The literature review covers the most common current in vitro, in vivo and in silico methods of studying transport into the brain, concentrating on transporter effects. The consequences of efflux mediated by p-glycoprotein, the most widely characterized transporter expressed at the BBB, is also discussed. The aim of the experimental study was to build a pharmacokinetic (PK) model to describe p-glycoprotein substrate drug concentrations in the brain using commonly measured in vivo parameters of brain distribution. The possibility of replacing in vivo parameter values with their in vitro counterparts was also studied. All data for the study was taken from the literature. A simple 2-compartment PK model was built using the Stella™ software. Brain concentrations of morphine, loperamide and quinidine were simulated and compared with published studies. Correlation of in vitro measured efflux ratio (ER) from different studies was evaluated in addition to studying correlation between in vitro and in vivo measured ER. A Stella™ model was also constructed to simulate an in vitro transcellular monolayer experiment, to study the sensitivity of measured ER to changes in passive permeability and Michaelis-Menten kinetic parameter values. Interspecies differences in rats and mice were investigated with regards to brain permeability and drug binding in brain tissue. Although the PK brain model was able to capture the concentration-time profiles for all 3 compounds in both brain and plasma and performed fairly well for morphine, for quinidine it underestimated and for loperamide it overestimated brain concentrations. Because the ratio of concentrations in brain and blood is dependent on the ER, it is suggested that the variable values cited for this parameter and its inaccuracy could be one explanation for the failure of predictions. Validation of the model with more compounds is needed to draw further conclusions. In vitro ER showed variable correlation between studies, indicating variability due to experimental factors such as test concentration, but overall differences were small. Good correlation between in vitro and in vivo ER at low concentrations supports the possibility of using of in vitro ER in the PK model. The in vitro simulation illustrated that in the simulation setting, efflux is significant only with low passive permeability, which highlights the fact that the cell model used to measure ER must have low enough paracellular permeability to correctly mimic the in vivo situation.