Testosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src-Dependent Pathways

Testosterone has been implicated in vascular remodeling associated with hypertension. Molecular mechanisms underlying this are elusive, but oxidative stress may be important. We hypothesized that testosterone stimulates generation of reactive oxygen species (ROS) and migration of vascular smooth muscle cells (VSMCs), with enhanced effects in cells from spontaneously hypertensive rats (SHRs). The mechanisms (genomic and nongenomic) whereby testosterone induces ROS generation and the role of c-Src, a regulator of redox-sensitive migration, were determined. VSMCs from male Wistar-Kyoto rats and SHRs were stimulated with testosterone (10(-7) mol/L, 0-120 minutes). Testosterone increased ROS generation, assessed by dihydroethidium fluorescence and lucigenin-enhanced chemiluminescence (30 minutes [SHR] and 60 minutes [both strains]). Flutamide (androgen receptor antagonist) and actinomycin D (gene transcription inhibitor) diminished ROS production (60 minutes). Testosterone increased Nox1 and Nox4 mRNA levels and p47phox protein expression, determined by real-time PCR and immunoblotting, respectively. Flutamide, actinomycin D, and cycloheximide (protein synthesis inhibitor) diminished testosterone effects on p47phox. c-Src phosphorylation was observed at 30 minutes (SHR) and 120 minutes (Wistar-Kyoto rat). Testosterone-induced ROS generation was repressed by 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day]pyrimidin-4-amine (c-Src inhibitor) in SHRs and reduced by apocynin (antioxidant/NADPH oxidase inhibitor) in both strains. Testosterone stimulated VSMCs migration, assessed by the wound healing technique, with greater effects in SHRs. Flutamide, apocynin, and 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day] pyrimidin-4-amine blocked testosterone-induced VSMCs migration in both strains. Our study demonstrates that testosterone induces VSMCs migration via NADPH oxidase-derived ROS and c-Src-dependent pathways by genomic and nongenomic mechanisms, which are differentially regulated in VSMCs from Wistar-Kyoto rats and SHRs. (Hypertension. 2012; 59: 1263-1271.). Online Data Supplement

Influence of children's oral health-related quality of life on school performance and school absenteeism

Objective: This study assessed the relation of child oral health-related quality of life with school performance and school absenteeism. Methods: We followed a cross-sectional design with a multistage random sample of 312 12-year-old schoolchildren living in Brazil. The participants completed the child perceptions questionnaire (CPQ1114) that provides information about psychological factors, while their parents or guardians answered questions on their socioeconomic status measured by parents' education level and household income. A dental examination of each child provided information on the prevalence of caries and dental trauma. Data on school performance, which included the results of baseline Brazilian language (Portuguese) tests, and school absenteeism (school days missed) were obtained from the school register. Multilevel linear regression was used to investigate the association among psychological and socioeconomic status and children's school performance. Results: In the multiple model, after adjusting for individual covariates, being a girl was associated with higher school performance (P < 0.05), whereas low household income (P < 0.05), higher mean of CPQ1114 (P < 0.05), and higher school days missed (P < 0.001) were identified as individual determinants of lower school performance. When the school-level covariates were included in the model, the association between subjects' level characteristics and school performance still persisted. Conclusion: Children's school performance and absence were influenced by psychological and socioeconomic conditions.