The margination propensity of spherical particles for vascular targeting in the microcirculation

The propensity of circulating particles to drift laterally towards the vessel walls (margination) in the microcirculation has been experimentally studied using a parallel plate flow chamber. Fluorescent polystyrene particles, with a relative density to water of just 50 g/cm3comparable with that of liposomal or polymeric nanoparticles used in drug delivery and bio-imaging, have been used with a diameter spanning over three order of magnitudes from 50 nm up to 10 mum. The number n approximately s MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmOvayLbaGaadaWgaaWcbaGaem4Camhabeaaaaa@2EB4@ of particles marginating per unit surface have been measured through confocal fluorescent microscopy for a horizontal chamber, and the corresponding total volume V approximately s MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmOvayLbaGaadaWgaaWcbaGaem4Camhabeaaaaa@2EB4@ of particles has been calculated. Scaling laws have been derived as a function of the particle diameter d. In horizontal capillaries, margination is mainly due to the gravitational force for particles with d > 200 nm and V approximately s MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmOvayLbaGaadaWgaaWcbaGaem4Camhabeaaaaa@2EB4@ increases with d4; whereas for smaller particles V approximately s MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmOvayLbaGaadaWgaaWcbaGaem4Camhabeaaaaa@2EB4@ increases with d3. In vertical capillaries, since the particles are heavier than the fluid they would tend to marginate towards the walls in downward flows and towards the center in upward flows, with V approximately s MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmOvayLbaGaadaWgaaWcbaGaem4Camhabeaaaaa@2EB4@ increasing with d9/2. However, the margination in vertical capillaries is predicted to be much smaller than in horizontal capillaries. These results suggest that, for particles circulating in an external field of volume forces (gravitation or magnetic), the strategy of using larger particles designed to marginate and adhere firmly to the vascular walls under flow could be more effective than that of using particles sufficiently small (d < 200 nm) to hopefully cross a discontinuous endothelium

Sistemas de informação geográfica aplicados ao cadastro urbano da cidade do Kilamba (Angola)

Project Work presented as the partial requirement for obtaining a Master's degree in Geographic Information Systems and ScienceOs Sistemas de Informação Geográfica (SIG) desempenham um papel fundamental no apoio à tomada decisão, tornando-se numa das tecnologias com mais projecção e desenvolvimento da actualidade. Pretendeu-se com o presente trabalho desenvolver um sistema aplicacional susceptível de ser posto em prática no apoio ao cumprimento na gestão do cadastro urbano da cidade do Kilamba. Explorando as capacidades dos SIG no auxílio à tomada de decisão, esta metodologia assenta em duas grandes aplicações: Microsoft Office Access - aplicação para apoio à gestão da informação não espacial e ArcGIS – na gestão das informações espacial. Como objectivos fulcrais das aplicações propostas salientam-se, para a primeira, a identificação das entidades, identificação das relações entre entidades, identificação dos atributos das entidades, consubstanciada na elaboração de diversas tabelas. Na segunda, foi criado uma base de dados geográfica (Geodatase) para armazenar toda a informação espacial e a importação dos dados não espaciais para estabelecer relacionamento entre entidade. Assim apresenta-se este trabalho de projecto na área dos SIG para a cidade do Kilamba, dando a conhecer os SIG e as suas potencialidades ao serviço da gestão do cadastro

Tailoring the degradation kinetics of mesoporous silicon structures through PEGylation

Injectable and implantable porosified silicon (pSi) carriers and devices for prolonged and controlled delivery of biotherapeutics offer great promise for treatment of various chronic ailments and acute conditions. Polyethylene glycols (PEGs) are important surface modifiers currently used in clinic mostly to avoid uptake of particlulates by reticulo-endothelial system (RES). In this work we show for the first time that covalent attachment of PEGs to the pSi surface can be used as a means to finely tune degradation kinetics of silicon structures. Seven PEGs with varying molecular weights (245, 333, 509, 686, 1214, 3400 and 5000Da) were employed and the degradation of PEGylated pSi hemispherical microparticles in simulated physiological conditions was monitored by means of ICP-AES, SEM and fluorimetry. Biocompatibility of the systems with human macrophages in vitro was also evaluated. The results clearly indicate that controlled PEGylation of silicon microparticles can offer a sensitive tool to finely tune their degradation kinetics and that the systems do not induce release of proinflammatory cytokines IL-6 and IL-8 in THP1 human macrophages

Single-step green synthesis and characterization of gold-conjugated polyphenol nanoparticles with antioxidant and biological activities

Background: Gold nanoparticles (GNPs) are likely to provide an attractive platform for combining a variety of biophysicochemical properties into a unified nanodevice with great therapeutic potential. In this study we investigated the capabilities of three different natural polyphenols, epigallocatechin-3-gallate (EGCG), resveratrol (RSV), and fisetin (FS), to allow synergistic chemical reduction of gold salts to GNPs and stabilization in a single-step green process. Moreover, antioxidant properties of the nanosystems, as well as preliminary antiproliferative activity and apoptotic process investigation of model EGCG-GNPs on stable clones of neuroblastoma SH-SY5Y cells expressing CFP-DEVD-YFP reporter, were examined. Methods: The GNPs were characterized by physicochemical techniques, polyphenol content, and in vitro stability. The antioxidant activity of the GNPs was also determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cation (ABTS) radical-scavenging assays. Stable clones of neuronal SH-SY5Y-CFP-DEVD-YFP were generated and characterized, and cell viability after treatment with EGCG-GNPs was assessed after 72 hours through a 3(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Activation of the apoptotic pathways was also investigated by Western blot analysis. Results: With a diameter in the size range of 10–25 nm, the obtained nanoparticles (NPs) were found to contain 2.71%, 3.23%, and 5.47% of EGCG, RSV, and FS, respectively. Nanoprototypes exhibited remarkable in vitro stability in various media, suggesting that NP surface coating with phytochemicals prevents aggregation in different simulated physiological conditions. The scavenging activities for DPPH and ABTS were highly correlated with EGCG, RSV, and FS content. Moreover, high correlation coefficients between the ABTS and DPPH values were found for the prepared nanosystems. EGCG-GNPs induce a dose-dependent reduction on SH-SY5Y-CFP-DEVD-YFP cell viability that is likely to involve the activation of the apoptotic pathways, similarly to free EGCG, as suggested by the processing of the CFP-DEVD-YFP reporter. Conclusion: These results prompted us to propose the ecofriendly synthesized EGCG-, RSV-, and FS-based nanogold conjugates as suitable carriers for bioactive polyphenols to be used for the treatment of disorders associated with oxidative stress, including neurodegenerative disorders, cardiovascular disease, and cancer.</br

De novo DNA methylation induced by circulating extracellular vesicles from acute coronary syndrome patients

DNA methylation is associated with gene silencing, but its clinical role in cardiovascular diseases (CVDs) remains to be elucidated. We hypothesized that extracellular vesicles (EVs) may carry epigenetic changes, showing themselves as a potentially valuable non-invasive diagnostic liquid biopsy. We isolated and characterized circulating EVs of acute coronary syndrome (ACS) patients and assessed their role on DNA methylation in epigenetic modifications

Brief episodes of silent atrial fibrillation predict clinical vascular brain disease in type 2 diabetic patients

ObjectivesThis study evaluated whether subclinical episodes of atrial fibrillation (AF) were associated with an increased risk of silent cerebral infarct (SCI) and stroke in diabetic patients younger than 60 years who did not have other clinical evidence of AF and cerebrovascular disease at baseline.BackgroundIn type 2 diabetic patients, one-fourth of strokes are of unknown cause, and subclinical episodes of AF may be a common etiologic factor.MethodsA total of 464 type 2 diabetic patients younger than 60 years were included in a longitudinal observational study and matched to patients without diabetes. Patients underwent 48-h electrocardiographic Holter monitoring quarterly to detect brief subclinical episodes of AF (duration of AF <48 h) and were followed up for 37 months. The outcomes were SCI, assessed by magnetic resonance imaging of the brain, and stroke events during the follow-up period.ResultsThe prevalence of subclinical episodes of AF was significantly greater among patients with diabetes compared with matched healthy subjects (11% vs. 1.6%, p < 0.0001). During an average duration of 37 months, 43 stroke events occurred in the diabetic population and no events occurred in healthy subjects. Diabetic patients with silent episodes of AF (n = 176) had a higher baseline prevalence of SCI (61% vs. 29%; p < 0.01) and a higher number of stroke events (17.3% vs. 5.9%; p < 0.01) during the follow-up period than the other patients (n = 288). An episode of silent AF was an independent determinant of SCI (odds ratio: 4.441; p < 0.001; confidence interval: 2.42 to 8.16) and an independent predictor of the occurrence of stroke in diabetic patients (hazard ratio: 4.6; p < 0.01; confidence interval: 2.7 to 9.1).ConclusionsSubclinical episodes of AF occurred frequently in type 2 diabetic patients and were associated with a significantly increased risk of SCI and stroke