Multiple Cytochrome P450 Isozymes in Murine Skin: Induction of P450 1A, 2B, 2E, and 3A by Dexamethasone

Cytochrome P450s (P450s) are a supergene family of enzymes responsible for the metabolism of a wide range of endogenous and foreign compounds. P450 isozymes possess overlapping substrate specificity. Systemic administration of dexamethasone, a widely used topical agent in dermatologic practice, to animals is known to result in the induction of multiple P450 isozymes in liver. In this study the effect of topical application of dexamethasone to mice on P450-dependent monooxygenase activities, expression of P450 isozymes, and P450 mRNA levels in skin was assessed. The treatment of mice with dexamethasone resulted in significant induction of 7-ethoxyresorufin O-deethylase (2.3 times), 7-pentoxyresorufin O-depentylase (19.2 times), para-nitrophenol hydroxylase (7.5 times), and erythromycin N-demethylase (2.2 times) activities; the monooxygenases catalyzed preferentially by P450 isozymes 1A1, 2B1, 2E1, and 3A, respectively. Immunoblot analysis of cutaneous microsomes, employing antibodies directed against purified P450s 1A1/2, 2B1/2, 2E1, and 3A, showed that dexamethasone treatment results in an increased immunoreactivity (1.8 – 13.9 times). In immunohistochemical staining of skin with antibody against P4502B1/2, topical application of dexamethasone resulted in an increased reactivity towards microsomal protein in the suprabasal layer of the epidermis and with the cells of the hair follicles. Whereas constitutive expression of mRNAs for CYP1A1 and CYP2E1 was evident in murine skin, any change in the levels of these mRNAs following treatment with dexamethasone was not apparent. The results of our study indicate that the application of dexamethasone to murine skin results in the induction of several families of P450 isozymes, suggesting that murine skin contains multiple inducible P450 isozymes capable of participating in the metabolism of a wide range of xenobiotics and endogenous compounds

Young European citizens : An individual by context perspective on adolescent European citizenship

This study examined the effects of individual, school-level and country-level variables and their interactions on two components of adolescents’ active European citizenship: trust in European institutions and participation at the European level. For comparison, country-related institutional trust and participation were also predicted. Using multilevel regression models, we re-analysed a subsample of survey data from the International Civic and Citizenship Education Study, collected from 14-year-old students (n = 72,466) in 22 European countries in 2009. Results showed that higher cognitive engagement with politics (e.g., political interest), more opportunities for learning about Europe at school, and country wealth and social equality were positively associated with both aspects of adolescents’ active European citizenship. In contrast to country-related participation, the participatory dimension of active European citizenship was also positively related to a higher socioeconomic status of adolescent’s classroom and family, an association that was more pronounced in less wealthy and post-communist countries

Acculturation in context: The moderating effects of immigrant and native peer orientations on immigrants’ acculturation experiences

Immigrant adolescents have to navigate through a complex social environment consisting of, at least, both a native and a co-ethnic community. This study used a multi-level framework to consider two research questions involving this complexity. The individual-level associations of acculturation orientations and acculturative hassles (language and sociocultural adaptation) was assessed in immigrant youths, and whether this association differs depending on the school-level acculturation orientations held by co-ethnic peers, and the school-level orientations toward immigrants held by native German peers. We then investigated whether acculturative hassles are associated with the psychosocial functioning (self-efficacy, depressive symptoms) of immigrant adolescents. The sample comprised 650 ethnic German Diaspora migrant adolescents (mean age 15.6 years, 53.7 % female) and their 787 native German peers (mean age 15.05 years, 51 % female). The results showed that contextual factors (co-ethnic acculturation orientation, native friendship preferences) moderated the association between the acculturation orientations of adolescent immigrants and both types of acculturative hassles. Acculturative hassles, in turn, were associated with the psychosocial functioning of adolescents. This research demonstrates that a person-by-context perspective is needed to better understand the adaptation of adolescent immigrants. This perspective has to take into account both the native and the co-ethnic peer environment