Too young to have sex: conversations with very young adolescents about sex, dating and related decision-making

Background. Very young adolescents receive little research and pragmatic attention regarding their sexual and reproductive health (SRH) needs. As a result, their experiences are often overlooked. Furthermore, when this age group is included in SRH education, the dominant public health lens tends to focus on health risks associated with sex, with less emphasis on a holistic approach that considers the socio-cultural and relational contexts in which adolescents' decision-making about sex and dating occurs. Objectives. To explore the beliefs, perceptions and decision-making pathways of adolescents about heterosexual sex, dating and relationships. Methods. The sample included 33 girls and 30 boys aged 10 - 14 years attending schools in rural Mpumalanga Province, South Africa. Data collection entailed participatory methodologies of group-based activities and individual interviews. Data were recorded and transcribed verbatim. Transcripts were coded and analysed using thematic analysis. Results. The findings focused on three themes: timing of dating, relationships and sex; gendered depictions of first sex; and agency in sexual decision-making. These themes shed light on the relational context in which adolescents' decision-making takes place and highlight the pervasive influence of wider gendered norms. Conclusion. Very young adolescents are not sexually naive and instead are faced with complex decisions regarding sex and dating. This age group is not, however, fully supported in developing a healthy, positive sexuality when emphasis is on the negative outcomes of sex. The paper concludes with recommendations for adolescent SRH programmes to provide a supportive environment for younger adolescents to make informed choices and develop positive, healthy sexualities

A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier.

Drug resistance is a major cause of chemotherapy failure in cancer treatment. One reason is the overexpression of the drug efflux pump P-glycoprotein (P-gp), involved in multidrug resistance (MDR). In vivo pharmacokinetic analysis of P-gp transport might identify the capacity of modulation by P-gp substrate modulators, such as cyclosporin A. Therefore, P-gp function was measured in vivo with positron emission tomography (PET) and [11C]verapamil as radiolabeled P-gp substrate. Studies were performed in rats bearing tumors bilaterally, a P-gp-negative small cell lung carcinoma (GLC4) and its P-gp-overexpressing subline (GLC4/P-gp). For validation, in vitro and biodistribution studies with [11C]daunorubicin and [11C]verapamil were performed. [11C]Daunorubicin and [11C]verapamil accumulation were higher in GLC4 than in GLC4/P-gp cells. These levels were increased after modulation with cyclosporin A in GLC4/P-gp. Biodistribution studies showed 159% and 185% higher levels of [11C]daunorubicin and [11C]verapamil, respectively, in GLC4 than in GLC4/P-gp tumors. After cyclosporin A, [11C]daunorubicin and [11C]verapamil content in the GLC4/P-gp tumor was raised to the level of GLC4 tumors. PET measurements demonstrated a lower [11C]verapamil content in GLC4/P-gp tumors compared with GLC4 tumors. Pretreatment with cyclosporin A increased [11C]verapamil levels in GLC4/P-gp tumors (184%) and in brains (1280%). This pharmacokinetic effect was clearly visualized with PET. These results show the feasibility of in vivo P-gp function measurement under basal conditions and after modulation in solid tumors and in the brain. Therefore, PET and radiolabeled P-gp substrates may be useful as a clinical tool to select patients who might benefit from the addition of a P-gp modulator to MDR drugs.

Carbon-11-labeled daunorubicin and verapamil for probing P-glycoprotein in tumors with PET.

UNLABELLED: One of the mechanisms for multidrug resistance (MDR) of tumors is an overexpression of the P-glycoprotein (P-gp). The cytostatic agent daunorubicin and the modulator verapamil were labeled with 11C to probe P-gp with PET. METHODS: Carbon-11-daunorubicin was prepared from 11CCH2N2 with an aldehyde precursor, followed by hydrolysis. Carbon-11-verapamil was synthesized by 11C-methylation. Both tracers were evaluated by investigating pharmacokinetics in rats and in vitro cell kinetics using human ovarian carcinoma cells. RESULTS: Amounts of 111 MBq 11C-daunorubicin were prepared. Biodistribution studies of 11C-daunorubicin in male Wistar rats showed dose-dependent pharmacokinetics, whereas with 11C-verapamil the pharmacokinetics were dose independent. In in vitro experiments with cells, the ratio of accumulation of 11C-daunorubicin in drug sensitive/resistant cell lines was 16. Addition of verapamil resulted in increased accumulation of 11C-daunorubicin in the resistant cell line. The ratios of 11C-verapamil accumulation in drug-sensitive versus the MDR counterpart were 4-5. CONCLUSION: Carbon-11-daunorubicin and 11C-verapamil both have potential for in vivo probing of P-glycoprotein with PET.