Propranolol Restricts the Mobility of Single EGF-Receptors on the Cell Surface before Their Internalization

The epidermal growth factor receptor is involved in morphogenesis, proliferation and cell migration. Its up-regulation during tumorigenesis makes this receptor an interesting therapeutic target. In the absence of the ligand, the inhibition of phosphatidic acid phosphohydrolase activity by propranolol treatment leads to internalization of empty/inactive receptors. The molecular events involved in this endocytosis remain unknown. Here, we quantified the effects of propranolol on the mobility of single quantum-dot labelled receptors before the actual internalization took place. The single receptors showed a clear stop-and-go motion; their diffusive tracks were continuously interrupted by sub-second stalling events, presumably caused by transient clustering. In the presence of propranolol we found that: i) the diffusion rate reduced by 22 %, which indicates an increase in drag of the receptor. Atomic force microscopy measurements did not show an increase of the effective membrane tension, such that clustering of the receptor remains the likely mechanism for its reduced mobility. ii) The receptor got frequently stalled for longer periods of multiple seconds, which may signal the first step of the internalization process

Suplementação com vitamina A: impacto na morbidade e efeitos adversos Vitamin A supplementation: impact on morbidity and adverse effects

Este artigo apresenta uma síntese de dois estudos previamente publicados e que avaliaram diferentes aspectos dos efeitos da suplementação com mega-doses (100.000 ou 200.000 UI) de vitamina A em crianças pré-escolares. O primeiro é um ensaio comunitário, aleatório, duplo cego e placebo controlado, que demonstrou o efeito positivo da suplementação na redução da severidade dos episódios de diarréia. O segundo investigou os potenciais efeitos adversos da suplementação com mega-doses de vitamina A, oferecida conjuntamente com a vacinação em massa, utilizando um desenho de intervenção controlado e não randomizado. Seus resultados indicaram que a suplementação associada com as vacinas rotineiramente utilizadas na infância não elevou as taxas de efeitos adversos (diarréia, febre e vômito). São ainda discutidas as implicações dos resultados destes estudos, que contribuíram não somente para o avanço do conhecimento científico do campo em questão, como também têm fornecido evidências para justificar a implementação de políticas e ações específicas no campo da saúde e da nutrição, que por sua vez têm contribuído para gerar condições mais auspiciosas de sobrevivência na infância. Discute-se também a pertinência e a utilidade de desenhos de estudo com diferentes níveis de rigor metodológico na avaliação de intervenção em saúde.<br>This paper is a synthesis of two previously published studies, which evaluated different aspects of the effects of massive doses of vitamin A (100,000 or 200,000 IU) in pre-school children. The first consisted of a randomized, double blind, placebo-controlled community trial, which demonstrated the effect of supplementation on the reduction of the severity of episodes of diarrhea. The second investigated the potential adverse effects of supplementation with massive doses of vitamin A when given during mass vaccination, using a controlled but not randomized intervention design. The results of this study showed that supplementation did not increase the rates of adverse effects (diarrhea, fever and vomiting) associated with the vaccines routinely used in infancy. In conclusion, we discuss the implications of the results of these studies, which contributed not only towards the advance of scientific knowledge in the field in question but also provided evidence to justify the implementation of policies and specific actions in the field of health and nutrition which have contributed towards creating better conditions for infant survival. We also discuss the pertinence and usefulness of study designs with different levels of methodological robustness in evaluations in health