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Roma-Rodrigues C.,UCIBIO | Fernandes A.R.,UCIBIO | Fernandes A.R.,University of Lisbon
Application of Clinical Genetics | Year: 2014

Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance. Due to the morphological and pathological heterogeneity of the disease, the appearance and progression of symptoms is not straightforward. Most HCM patients are asymptomatic, but up to 25% develop significant symptoms, including chest pain and sudden cardiac death. Sudden cardiac death is a dramatic event, since it occurs without warning and mainly in younger people, including trained athletes. Molecular diagnosis of HCM is of the outmost importance, since it may allow detection of subjects carrying mutations on HCM-associated genes before development of clinical symptoms of HCM. However, due to the genetic heterogeneity of HCM, molecular diagnosis is difficult. Currently, there are mainly four techniques used for molecular diagnosis of HCM, including Sanger sequencing, high resolution melting, mutation detection using DNA arrays, and next-generation sequencing techniques. Application of these methods has proven successful for identification of mutations on HCM-related genes. This review summarizes the features of these technologies, highlighting their strengths and weaknesses. Furthermore, current therapeutics for HCM patients are correlated with clinically observed phenotypes and are based on the alleviation of symptoms. This is mainly due to insufficient knowledge on the mechanisms involved in the onset of HCM. Tissue engineering alongside regenerative medicine coupled with nanotherapeutics may allow fulfillment of those gaps, together with screening of novel therapeutic drugs and target delivery systems. © 2014 Chaudhary and Al-Baradie. Source

Vieira A.C.C.,UCIBIO | Chaves L.L.,UCIBIO | Pinheiro M.,UCIBIO | Ferreira D.,Laboratory of Pharmaceutical Technology | And 4 more authors.
International Journal of Nanomedicine | Year: 2016

The aim of the present work was to develop and optimize surface-functionalized solid lipid nanoparticles (SLNs) for improvement of the therapeutic index of dapsone (DAP), with the application of a design of experiments. The formulation was designed to target intestinal microfold (M-cells) as a strategy to increase internalization of the drug by the infected macrophages. DAP-loaded SLNs and mannosylated SLNs (M-SLNs) were successfully developed by hot ultrasonication method employing a three-level, three-factor Box–Behnken design, after the preformulation study was carried out with different lipids. All the formulations were systematically characterized regarding their diameter, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity. They were also subjected to morphological studies using transmission electron microscopy, in vitro release study, infrared analysis (Fourier transform infrared spectroscopy), calorimetry studies (differential scanning calorimetry), and stability studies. The diameter of SLNs, SLN-DAP, M-SLNs, and M-SLN-DAP was approximately 300 nm and the obtained PDI was < 0.2, confirming uniform populations. Entrapment efficiency and loading capacity were approximately 50% and 12%, respectively. Transmission electron microscopy showed spherical shape and nonaggregated nanoparticles. Fourier transform infrared spectroscopy was used to confirm the success of mannose coating process though Schiff's base formation. The variation of the ZP between uncoated (approximately –30 mV) and mannosylated formulations (approximately +60 mV) also confirmed the successful coating process. A decrease in the enthalpy and broadening of the lipid melting peaks of the differential scanning calorimetry thermograms are consistent with the nanostructure of the SLNs. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. Storage stability for the formulations for at least 8 weeks is expected, since they maintain the original characteristics of diameter, PDI, and ZP. These results pose a strong argument that the developed formulations can be explored as a promising carrier for treating leprosy with an innovative approach to target DAP directly to M-cells. © 2016 Vieira et al. Source

Hilliou L.,Institute for Polymers and Composites | Machado D.,Institute for Polymers and Composites | Oliveira C.S.S.,UCIBIO | Gouveia A.R.,UCIBIO | Reis M.A.M.,UCIBIO
Journal of Applied Polymer Science | Year: 2015

The effects of recovered residues on the characteristics of polyhydroxy(butyrate-co-valerate) (PHBV) produced from mixed microbial cultures (MMCs) fed with cheese whey, olive oil mill wastewater, or a synthetic mixture of acetic and propionic acid were investigated. The different types of MMC PHBVs were extracted and purified with different downstream routes; this enabled the recovery of polymers with different hydroxyvalerate contents and different residue types and levels, ranging from 0 to 11%. The results indicate overall that the recovery of residues together with the biopolymer brought benefits to the melt processability of these MMC PHBVs. Impurities triggered thermal degradation at smaller temperatures, promoted melting at lower temperatures, acted as thermal stabilizers, improved the melt viscosity, and enhanced the shear thinning. The degree of crystallinity of the aged samples was not affected by the impurities, but the crystallites size increased. MMC PHBVs recovered with residues containing more proteins showed better thermal stability, whereas MMC PHBVs containing more inorganic residues showed better melt viscoelastic properties. The results of this study show that impurities recovered together with the MMC PHBVs introduced changes to their thermal, semicrystalline, and rheological properties; these changes, in some cases, were detrimental, but they were also potentially advantageous to the processing and conversion of these materials into products such as packages. © 2015 Wiley Periodicals, Inc. Source

Pedrosa P.,UCIBIO | Vinhas R.,UCIBIO | Fernandes A.,UCIBIO | Baptista P.V.,UCIBIO
Nanomaterials | Year: 2015

Nanoparticles have been making their way in biomedical applications and personalized medicine, allowing for the coupling of diagnostics and therapeutics into a single nanomaterial—nanotheranostics. Gold nanoparticles, in particular, have unique features that make them excellent nanomaterials for theranostics, enabling the integration of targeting, imaging and therapeutics in a single platform, with proven applicability in the management of heterogeneous diseases, such as cancer. In this review, we focus on gold nanoparticle-based theranostics at the lab bench, through pre-clinical and clinical stages. With few products facing clinical trials, much remains to be done to effectively assess the real benefits of nanotheranostics at the clinical level. Hence, we also discuss the efforts currently being made to translate nanotheranostics into the market, as well as their commercial impact. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source

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