ABSTRACT
Nanoparticles are a promising cancer therapy for their use as drug carriers given their versatile functionalization with polyethylene glycol and proteins that can be recognized by overexpressed receptors in tumor cells. However, it has been suggested that in biological fluids, proteins cover nanoparticles, which gives the proteins a biological identity that could be responsible for unexpected biological responses: the so-called protein corona. A relevant biological event that is usually ignored in protein-corona formation is the interspecies differences in protein binding, which can be involved in the discrepancies observed in preclinical studies and the nanoparticle safety and efficiency. Hence, the aim of this study was to determine the differences between human and mouse plasma protein corona profiles in an active therapy model using silicon dioxide nanoparticles (SiO2 nanoparticles) functionalized with polyethylene glycol and transferrin. Functionalized SiO2 nanoparticles were made with a primary particle size of 25 nm and a transferrin content of 50 µg mg-1 of nanoparticles and were PEGylated with a cross-linker. The proteomic analysis by nanoliquid chromatography tandem-mass spectrometry (nanoLC-MS/MS) showed interspecies differences. The most abundant proteins found in the human protein corona profile were immunoglobulins, actin cytoplasmic 1, hemoglobin subunit beta, serotransferrin, ficolin-3, complement C3, and apolipoprotein A-1. Meanwhile, the mouse protein corona adsorbed the serine protease inhibitor A3K, serotransferrin, alpha-1-antitrypsin 1-2, hemoglobin subunit beta, and fibrinogen gamma and beta chains. These protein-corona profile differences in the functionalized SiO2 nanoparticles indicate that biological responses observed in in vivo models could not be translated to clinical use and must be considered in the interpretation of preclinical trials in order to design more efficient and safer nanomedicines.
Subject(s)
Nanoparticles , Protein Corona/analysis , Silicon Dioxide , Animals , Chromatography, Liquid , Humans , Male , Mice , Mice, Inbred BALB C , Proteomics , Tandem Mass SpectrometryABSTRACT
Este artículo resume una propuesta organizacional para la atención de salud rural, realizada a solicitud del Servicio de Salud Llanquihue Chiloé Palena, por los autores entre enero y abril del 2007. Realiza un análisis esencialmente cualitativo de la situación rural en el área del Servicio de Salud y un diagnóstico centrado en una hipótesis unitaria: la salud rural ha extraviado el espíritu que la animó en las décadas precedentes. Del diagnóstico se desprende la identidad territorial y el conocimiento local como pilares indispensables para recuperar ese espíritu. La propuesta se centra en la construcción de equipos territoriales, autónomos y públicos.
This paper is a summary of an organizational proposal for rural health. Between January and April 2007 we prepared a document requested by Llanquihue Chiloé Palena Health Service. We did a research and qualitative diagnosis of rural health situation in Health Service area. Our analysis is based in a unitary hypothesis: rural health has loosed its spirit. From the diagnosis we recognized territorial identity and local knowledge as essentials tools for the spirit recovery. The proposal is then focused in the construction of public, autonomic and territorial health teams.
Subject(s)
Humans , Local Health Strategies , Rural Health , Chile , Diagnosis of Health Situation , Community ParticipationABSTRACT
O objetivo deste trabalho foi avaliar parâmetros genéticos e de ambiente de algumas medidas de tamanho corporal em 667 fêmeas adultas da raça Guzerá. Medidas de tamanho corporal, peso à maturidade (PM), circunferência torácica (CT), alturas de cernelha (AC) e de garupa (AG) e comprimento corporal (CC) foram realizadas em duas épocas distintas. As análises estatísticas foram feitas pelo método dos quadrados mínimos com números desiguais nas subclasses. Devido às oscilaçöes de PM e CT em funçäo do estado fisiológico, estas medidas foram ajustadas previamente para os efeitos de tempo de gestaçäo (mais de seis/menos de seis meses de gestaçäo) e condiçäo de amamentaçäo (seca/lactante). As análises de variância revelaram efeitos significativos de touro dentro de fazenda, fazenda e ano-estaçäo de nascimento (P<0,05), com exceçäo do efeito de ano-estaçäo de nascimento para CT, AC, AG e CC. As médias dos quadrados mínimos para as características de tamanho corporal foram 447ñ3,7kg para PM, 182,2ñ0,6cm para CT, 135ñ0,4cm para AC, 140ñ0,4cm para AG e 146ñ0,5cm para CC. As estimativas de herdabilidade, na mesma ordem, foram as seguintes: 0,45ñ0,14, 0,52ñ0,15, 0,68ñ0,15, 0,69ñ0,15 e 0,41ñ0,14. As correlaçöes genéticas (rG) entre as características PM-CT, PM-AC, PM-AG, PM-CC, CT-AC, CT-AG, CT-CC, AC-AG, AC-CC e AG-CC, foram, nesta ordem: 0,87ñ0,07, 0,79ñ0,11, 0,68ñ0,13, 0,96ñ0,12, 0,70ñ0,12, 0,48ñ0,16, 0,67ñ0,17, 0,95ñ0,03, 0,72ñ0,13 e 0,64ñ0,15. As correlaçöes fenotípicas (rP), na mesma seqüência, foram: 0,82, 0,57, 0,54, 0,56, 0,54, 0,48, 0,42, 0,86,0,53 e 0,52. Os elevados valores das rG e rP entre as medidas de tamanho corporal evidenciam que a seleçäo para uma ou mais medidas levará a respostas correlacionadas nas demais