Youth and Their Parents' Views on the Acceptability and Design of a Video-Based Tobacco Prevention Intervention

The purpose of this study was to evaluate the acceptability of a brief, video-based parental intervention that modeled parent-child communication about tobacco, delivered within an emergency department (ED) setting. While waiting to be seen by a physician in the ED, 20 parent-youth dyads watched the video together and then private, semi-structured focused interviews were conducted around the "take home" message and views on the settings, actors, and content of the videos. Dyads agreed that the design, delivery, and content of the video intervention were acceptable, realistic, and useful in providing parental reinforcements about the importance of parent-youth tobacco communication and the ED was considered to be a good setting for watching the video. Our findings support the development and delivery of such an ED intervention and aids in determining content and scenarios for future intervention development.     

Bioactive xanthones with effect on P-glycoprotein and prediction of intestinal absorption

Our research group has been focusing in the discovery of potential antitumor small molecules based on the xanthone scaffold. However, a serious obstacle in the field of cancer therapy is the multidrug resistance (MDR) phenotype, most often caused by the overexpression of P-glycoprotein (P-gp). Another limitation to development of such drug candidates is the reduced information available about the bioavailability of these compounds. We have previously identified four interesting compounds as inhibitors of tumor cell growth namely two dihydroxyxanthones, a xanthonolignoid and a pyranoxanthone. Based on these considerations, it was our aim to: (i) investigate their effect on the P-gp activity; and (ii) estimate their intestinal absorption using Caco-2 cell monolayers as an intestinal model. An HPLC analysis from the in vitro permeation assay with Caco-2 cells monolayer was performed to predict the intestinal permeability of xanthonic derivatives. A rhodamine (Rh123) accumulation assay using P-gp overexpressing leukemia cells, K562Dox, incubated with the four xanthonic derivatives, was performed to investigate their P-gp inhibitory activity. A luminescence-based ATPase assay was performed to differentiate between competitive and noncompetitive P-gp inhibitors. The xanthonolignoid and the pyranoxanthone were found to increase the accumulation of Rh123 in K562Dox cell line, and both were acting by a noncompetitive P-gp inhibitory mechanism. Transport of the four xanthones occurred in the absorptive direction (P_app, 0.012–2.8 nm/s). The behavior of the xanthonolignoid and the pyranoxanthone as P-gp inhibitors and their high apparent permeability coefficients make them promising hit compounds to pursue with further studies.     

Driving GDNF expression: the green and the red traffic lights

Glial cell line-derived neurotrophic factor (GDNF) is widely recognized as a potent survival factor for dopaminergic neurons of the nigrostriatal pathway that degenerate in Parkinson's disease (PD). In animal models of PD, GDNF delivery to the striatum or the substantia nigra protects dopaminergic neurons against subsequent toxin-induced injury and rescues previously damaged neurons, promoting recovery of the motor function. Thus, GDNF was proposed as a potential therapy to PD aimed at slowing down, halting or reversing neurodegeneration, an issue addressed in previous reviews. However, the use of GDNF as a therapeutic agent for PD is hampered by the difficulty in delivering it to the brain. Another potential strategy is to stimulate the endogenous expression of GDNF, but in order to do that we need to understand how GDNF expression is regulated. The aim of this review is to do a comprehensive analysis of the state of the art on the control of endogenous GDNF expression in the nervous system, focusing mainly on the nigrostriatal pathway. We address the control of GDNF expression during development, in the adult brain and after injury, and how damaged neurons signal glial cells to up-regulate GDNF. Pharmacological agents or natural molecules that increase GDNF expression and show neuroprotective activity in animal models of PD are reviewed. We also provide an integrated overview of the signalling pathways linking receptors for these molecules to the induction of GDNF gene, which might also become targets for neuroprotective therapies in PD.     

Genomic ancestry in urban Afro-Brazilians

Brazil is the result of interethnic crosses of European, African and Amerindian populations. Allelic frequencies for seven STR loci (TH01, TPOx, CSF1PO, vWA, FES/FPS, F13A1 and CD4), obtained from a sample of 70 individuals identified as Afro-Brazilian and 150 as mulatto, are presented here. Based on the frequencies of these genetic markers, estimates of interethnic admixture showed 62%, 26% and 12% of European, African and Amerindian contribution, respectively, for the mulatto sample and 37% and 63% of European and African contribution, respectively, for the Afro-Brazilian sample.     

Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model

Inhibition of VEGF signalling effectively suppresses localized tumour growth but accelerates tumour invasiveness and micrometastasis by unknown mechanisms. To study the dynamic and reciprocal interactions between tumour cells and their microenvironment during these processes, we established a xenograft model by injecting tumour cells into the blood circulation of transparent zebrafish embryos. This reproducibly results in rapid simultaneous formation of a localized tumour and experimental micrometastasis, allowing time-resolved imaging of both processes at single-cell resolution within 1 week. The tumour vasculature was initiated de novo by remodelling of primitive endothelial cells into a functional network. Roles of myeloid cells in critical tumourigenesis steps such as vascularization and invasion were revealed by genetic and pharmaceutical approaches. We discovered that the physiological migration of neutrophils controlled tumour invasion by conditioning the collagen matrix and forming the metastatic niche, as detected by two-photon confocal microscopy and second harmonic generation. Administration of VEGFR inhibitors blocked tumour vascularization and a localized tumour growth but enhanced migration of neutrophils, which in turn promoted tumour invasion and formation of micrometastasis. This demonstrates the in vivo cooperation between VEGF signalling and myeloid cells in metastasis and provides a new mechanism underlying the recent findings that VEGFR targeting can promote tumour invasiveness.     

Qualitative assessment of the environment in a Psychosocial Care Center

This study is based on a cross-section of the study of Psychosocial Care Center (Caps) in the South of Brazil. Objective: to conduct a qualitative assessment of the structure, in terms of environment, of a Caps in the interior of the State of Rio Grande do Sul. A case study was conducted on the Caps in Alegrete (RS) based on a fourth generation, constructivist and responsive assessment using a hermeneutic-dialectic approach. The data collection instruments were semi-structured interviews with a team (26), users (11), and family members (14), defined as interest groups to make up the hermeneutic-dialectic circle and field observation (390 hours) establishing prior ethnography. The structure of the Alegrete Caps was a strong aspect in the environmental evaluation. The lack of human and material resources does not interfere directly in user satisfaction with the environment.     

Modelling future renal dialysis requirements under various scenarios of organ availability in Australia

SUMMARY: The rate of dialysis uptake in Australia has been increasing and in 1996 was 77 per million people per year (pmp). The rate of kidney transplantation in Australia is at the same time falling. We have developed a computer model to enable predictions of the number of dialysis patients to 2007, under several scenarios of organ availability. We also aimed to examine the cost implications of the predictions. The number of existing and new dialysis and transplant patients was obtained from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) for the years 1988–95. Age‐stratified transition coefficients for dialysis uptake, transplantation, graft failure and dialysis and transplant death were calculated for this time period. Data from 1995 were used as the baseline year in the application of the model and the calculated transition coefficients applied for this year. Scenarios of organ availability examined were the current trend continued, stabilization of the current Australian rate (23 pmp), the South Australian rate (35 pmp) achieved nationally and the Spanish rate (47 pmp) achieved nationally. Validation of the model using 1997 data was performed. Direct costs for dialysis and transplantation were obtained from a major teaching hospital in Melbourne. The number on dialysis is predicted to increase from 5648 in 1998 to 11 803 by 2007. If the transplant rate is increased from 23 pmp to ‘the world best practice transplantation rate’ (47 pmp) the predicted dialysis number in 2007 would be 8476. This is associated with a direct cost saving in comparison to the current trend of 82 million dollars (1998 Australian dollars). Assuming the Australian population increases as predicted and that current trends in dialysis uptake and transplantation continue, dialysis numbers are predicted to more than double over the next 10 years. In order to limit the potential human and economic cost of renal replacement therapy, this model indicates that attempts to increase organ availability are worthwhile.