Alocação Renal: Novas Contribuições para um Desafio Permanente

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Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells

The main aim of this work was to develop novel targeted sterically stabilised pH-sensitive liposomes tailored to promote efficient intracellular delivery of therapeutic molecules into human T-leukaemia cells. Our results indicate that the targeting moiety (thiolated transferrin) was successfully coupled to the distal reactive maleimide terminus of poly(ethylene glycol)-phospholipid conjugates incorporated in the liposomal bilayer. Results from atomic force microscopy studies, performed to characterise vesicle surface topology, indicated that, to a certain extent, thiolated transferrin has the ability to associate in a non-specific manner with the lipid membrane of pegylated liposomes. This is an issue not commonly reported in the literature but which is crucial to demonstrate the targeting proof of principle. Nevertheless, fluorimetric studies together with confocal microscopy clearly demonstrate that liposomes bearing covalently coupled transferrin associate more extensively to human T-leukaemia cells in vitro than non-targeted liposomes. Cell mechanistic studies indicate that targeted liposomes bind specifically to transferrin receptors and are internalised via receptor-dependent endocytotic pathway. In addition, the biophysical features exhibited by the developed liposomes, namely their ability to promote pH-triggered cytoplasmic delivery of loaded material, make them promising delivery systems for in vivo targeting of therapeutic molecules to tumours.http://www.sciencedirect.com/science/article/B6T6C-4DVT9WH-1/1/5592c4a7248e7be29f239e55046f842

A Physiological Approach to Recurrent Nephrolithiasis and its Genetic Determinants

We report a case of a 63-year-old patient with recurrent nephrolithiasis for over 40 years and a significant family history of nephrolithiasis. The patient underwent full investigation at our department. He presented hypercalcemia, hypophosphatemia and hypercalciuria, with parathyroid hormone level in the normal range. A calcium load test and a fluorocholine PET-CT excluded primary hyperparathyroidism. Abnormal secretion of parathyroid hormone-related protein and sarcoidosis were also excluded. Genetic analysis showed mutations encoding for 25(OH)-vitamin D3-24-hydroxylase (CYP24A1) and Na-dependent phosphate cotransporter 2c (SLC34A3). This case affords insights into the biological pathways that underlie the role of genetic inheritance and accrued risk of development of nephrolithiasis.info:eu-repo/semantics/publishedVersio

The association between 25(OH)D levels, frailty status and obesity indices in older adults

Background: Vitamin D deficiency is common in older adults and has been linked with frailty and obesity, but it remains to be studied whether frail obese older adults are at higher risk of vitamin D deficiency. Therefore, the aim of this study is to explore the association between frailty, obesity indices and serum 25(OH)D concentrations. Methods: 1447 individuals with 65 years or older, participating in a cross-sectional study (Nutrition UP 65) were included. Frailty, according to Fried et al., body mass index (BMI), waist circumference (WC), body roundness index (BRI) and body shape index (ABSI) were evaluated. A stepwise multinomial logistic regression was carried out to quantify the association between 25(OH)D quartiles and independent variables. Results: Median 25(OH)D levels were lower in individuals presenting both frailty and obesity (p<0.001). In the multivariate analysis, pre-frailty (OR: 2.65; 95% CI: 1.63-4.33) and frailty (OR: 3.77; 95% CI: 2.08-6.83) were associated with increased odds of lower 25(OH)D serum levels (first quartile). Regarding obesity indices, the highest categories of BMI (OR: 1.74; 95% CI: 1.06-2.86), WC (OR: 3.46; 95% CI: 1.95-6.15), BRI (OR: 4.35; 95% CI: 2.60-7.29) and ABSI (OR: 3.17 95% CI: 1.86-5.38) were directly associated with lower 25(OH)D serum levels (first quartile). Conclusions: A positive association between frailty or obesity and lower vitamin D levels was found. Moreover, besides BMI and WC, other indicators of body adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations.info:eu-repo/semantics/publishedVersio

Advanced antibacterial wound dressing produced with natural-origin materials

Portuguese Foundation for Science and Technology for the OsteoGraphy (PTDC/EME- MFE/2008) and MaxBone (PTDC/SAU -ENB/115179/2009) project. This work was partly supported by “RL1 - ABMR - NORTE-01-0124- FEDER-000016” cofinanced by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF) project.

The modulation of the symbiont/host interaction between wolbachia pipientis and aedes fluviatilis embryos by glycogen metabolism

Wolbachia pipientis, a maternally transmitted bacterium that colonizes arthropods, may affect the general aspects of insect physiology, particularly reproduction. Wolbachia is a natural endosymbiont of Aedes fluviatilis, whose effects in embryogenesis and reproduction have not been addressed so far. In this context, we investigated the correlation between glucose metabolism and morphological alterations during A. fluviatilis embryo development in Wolbachia-positive (W+) and Wolbachia-negative (W2) mosquito strains. While both strains do not display significant morphological and larval hatching differences, larger differences were observed in hexokinase activity and glycogen contents during early and mid-stages of embryogenesis, respectively. To investigate if glycogen would be required for parasite-host interaction, we reduced Glycogen Synthase Kinase-3 (GSK-3) levels in adult females and their eggs by RNAi. GSK-3 knock-down leads to embryonic lethality, lower levels of glycogen and total protein and Wolbachia reduction. Therefore, our results suggest that the relationship between A. fluviatilis and Wolbachia may be modulated by glycogen metabolism

Induction of human mesenchymal stem cells osteogenesis by bioactive agent-releasing liposomes

Stem cell therapy is a rapidly evolving area of research in regenerative medicine. Mesenchymal stem cells (MSCs) have received considerable attention by the scientific community because of their potential of expansion and the ability to differentiate into various mesodermal tissues. Liposomes are well-established non-viral carrier systems, presenting significant advantages over other nanoparticle-based drug delivery systems, namely a high load carrying capacity, a relative safety and an ease of large-scale production, as well as a versatile nature in terms of possible formulation and functionalization. The objectives of the present study were to evaluate the efficacy of growth differentiation factor-releasing liposomes on the induction of MSCs osteogenesis. For that, dexamethasone (Dex) was encapsulated within the liposome bilayer at different lipid formulations. The obtained liposomes showed a monodisperse distribution of particles size, and an increased ζ- potential for the PEGylated liposomes. Dex encapsulation studies demonstrate that the presence of cholesterol (Chol) decreases the Dex loading capacity of the liposome bilayer. The different stabilizing effect of Chol and Dex on the liposomes is due to differences in their interaction with phospholipid molecules. Highly lipophilic Chol gets incorporated between the acyl chains and reduces chain movement increasing rigidity and stabilization the membrane. Dex, being more hydrophilic, interacts differently with phospholipid acyl chains and head groups and destabilizes the membrane. In vitro release study demonstrated an initial burst release within an initial timeframe of 24 hours. Following the initial release, a slower release was observed until 6 days. Afterwards, Dex continues to be released at a slower but steady rate until day 21. The effect of Dex-loaded liposomes on viability, proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) was assessed. The results of the biological activity showed that the Dex-loaded liposomes do not have any cytotoxic effect and, more importantly, were able to promote an earlier induction of hBMSCs differentiation into the osteogenic lineage, as demonstrated by the expression of osteoblastic markers at the phenotypic and the genotypic levels. Concluding, Dex-loaded liposomes represent a novel biological or nature-inspired nanoparticle strategy for tissue engineering and regenerative medicine applications

Mycobacterium Bovis em queijo coalho artesanal em Parnaíba, Piauí.

O objetivo desse estudo foi detectar Mycobacterium bovis em queijo de coalho artesanal comercializado em Parnaíba, Piauí, por meio de cultivo microbiológico e pela Reação em Cadeia de Polimerase em Tempo Real