which normally promote and inhibit acquisition of the EGF receptor, respectively. Tenascin C-deficient mice also have altered numbers of CNS stem cells and these stem cells have an increased probability of generating neurones when grown in cell culture. We conclude that tenascin C contributes to the generation of a stem cell 'niche' within the SVZ, acting to orchestrate growth factor signalling so as to accelerate neural stem cell development.
Oral route is the most common route for the delivery of drugs because it is simple to implement and improves patient compliance and quality of life. However, oral absorption is limited by various physiological barriers and remains a scientific challenge. Nanometric-sized drug delivery systems are being extensively studied and provide promising potential for oral drug delivery. Many different technological solutions have been proposed to enhance the bioavailability or the targeting of drug after oral administration. To reach these goals, it is important to analyze the biopharmaceutical parameters to consider in order to alter the fate of nanocarriers after oral delivery. In the present review, the gastrointestinal barrier and physiological stress factors with regard to nanocarriers' performance or integrity issues are first described. Second, the different characteristics offered by the nanocarriers (size, surface composition and properties mediated by external factors such as ligands) and their effect on the optimal transport of drug into the bloodstream are discussed. Finally, the integrity issue is discussed in function of the expected role of the nanocarriers: bioavailability enhancement or pharmacological targeting.
Astrocytes play a pivotal role in CNS detoxification pathways, where glutathione (GSH) is involved in the elimination of oxygen and nitrogen reactive species such as nitric oxide. We have previously demonstrated that the specific activity of ␥-glutamyl transpeptidase (␥-GT), an enzyme of central significance in GSH metabolism, is regulated in vivo in astrocytes by 1,25-dihydroxyvitamin D 3 (1,25-D 3 ). The aim of the present work was to investigate, in primary cultures of newborn rat astrocytes, the effects of this hormone on ␥-GT synthesis and on GSH and nitrite levels after lipopolysaccharide (LPS) treatment. This study demonstrates that both ␥-GT gene expression and specific activity, induced by LPS, are potentiated by 1,25-D 3 . In contrast, 1,25-D 3 does not regulate the expression of other enzymes involved in astrocyte detoxification processes, such as superoxide dismutase or GSH peroxidase. In parallel, 1,25-D 3 enhanced intracellular GSH pools and significantly reduced nitrite production induced by LPS. Taken together, these results suggest that ␥-GT, GSH, and 1,25-D 3 play a fundamental role in astrocyte detoxification pathways.
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