Icvs 3Bs Pt Government Assoct Laboratory

Braga, Portugal

Icvs 3Bs Pt Government Assoct Laboratory

Braga, Portugal

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Cunha P.G.,Guimaraes Centro Hospitalar Do Alto Ave | Cunha P.G.,University of Minho | Cunha P.G.,Icvs 3Bs Pt Government Assoct Laboratory | Cotter J.,Guimaraes Centro Hospitalar Do Alto Ave | And 11 more authors.
Journal of Hypertension | Year: 2015

Background: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. Method: Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. Results: Mean PWV value for the entire population was 8.4 m/s (men: 8.6 m/s; women: 8.2 m/s; P<0.02). The individuals were classified with EVA if their PWV was at least 97.5th percentile of z-score for mean PWV values adjusted for age (using normal European reference values as comparators). The overall prevalence of EVA was 12.5%; 26.1% of individuals below 30 years presented this feature and 40.2% of individuals in that same age strata were placed above the 90th percentile of PWV; and 18.7% of the population exhibited PWV values above 10 m/s, with male predominance (17.2% of men aged 40-49 years had PWV>10 m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10 m/s 10 years later than men. Conclusion: The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Esteves S.,University of Minho | Esteves S.,Icvs 3Bs Pt Government Assoct Laboratory | Duarte-Silva S.,University of Minho | Duarte-Silva S.,Icvs 3Bs Pt Government Assoct Laboratory | And 10 more authors.
PLoS ONE | Year: 2015

Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics. © 2015 Esteves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Oliveira T.G.,University of Minho | Oliveira T.G.,Icvs 3Bs Pt Government Assoct Laboratory | Chan R.B.,Columbia University | Chan R.B.,Columbia University Medical Center | And 18 more authors.
Molecular Psychiatry | Year: 2016

Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits. © 2016 Macmillan Publishers Limited All rights reserved.

Teixeira-Castro A.,University of Minho | Teixeira-Castro A.,Icvs 3Bs Pt Government Assoct Laboratory | Teixeira-Castro A.,Northwestern University | Jalles A.,University of Minho | And 28 more authors.
Brain | Year: 2015

Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and reduced aggregation using a Caenorhabditis elegans model of mutant ataxin 3-induced neurotoxicity. MOD-5, the C. elegans orthologue of the serotonin transporter and cellular target of citalopram, and the serotonin receptors SER-1 and SER-4 were strong genetic modifiers of ataxin 3 neurotoxicity and necessary for therapeutic efficacy. Moreover, chronic treatment of CMVMJD135 mice with citalopram significantly reduced ataxin 3 neuronal inclusions and astrogliosis, rescued diminished body weight and strikingly ameliorated motor symptoms. These results suggest that small molecule modulation of serotonergic signalling represents a promising therapeutic target for Machado-Joseph disease. © 2015 The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reys L.L.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Reys L.L.,Icvs 3Bs Pt Government Assoct Laboratory | Silva S.S.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Silva S.S.,Icvs 3Bs Pt Government Assoct Laboratory | And 10 more authors.
ACS Biomaterials Science and Engineering | Year: 2016

Algae are abundant sources of bioactive components with extensive therapeutic properties, receiving much interest in recent years. The research on marine brown algae, namely one of its polysaccharide-fucoidan, has increased exponentially. Fucoidan is a sulfated cell-wall polysaccharide with several reported biological properties including anticancer, antivirus, anticoagulant, antioxidant and anti-inflammatory effects. In this study, fucoidan was functionalized by grafting methacrylic groups in the chain backbone, photo-cross-linkable under visible light to obtain biodegradable structures for tissue engineering. The functionalization reaction was carried out by concentrations (8 and 12%) of methacrylic anhydride (MA). The modified fucoidan (MFu) was characterized by FTIR and 1HNMR spectroscopy to confirm the functionalization. Further, modified fucoidan was photo-cross-linked under visible light and using superhydrophobic surfaces, to obtain spherical particles with controlled geometries benefiting from the high repellence of the surfaces. When using higher concentrations of MA, the particles were observed to exhibit a smaller average diameter. Moreover, the behavior of L929 mouse fibroblast-like cells was evaluated when cultured in contact with photo-cross-linked particles was investigated, being observed up to 14 days in culture. The photo-cross-linking of MFu under visible light enables thus the formation of particles here suggested as potentially relevant in a wide range of biomedical applications. © 2016 American Chemical Society.

Fernandes J.S.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Fernandes J.S.,Icvs 3Bs Pt Government Assoct Laboratory | Martins M.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Martins M.,Icvs 3Bs Pt Government Assoct Laboratory | And 7 more authors.
ACS Biomaterials Science and Engineering | Year: 2016

Three novel borosilicate bioactive glasses (BBGs) were prepared and used to investigate their bioactive and antibacterial properties. The BBGs were prepared by melt-quenching using different glass modifiers, i.e. Mg2+, Ca2+, and Sr2+, and their amorphous nature was confirmed by X-ray diffraction. Scanning electron microscopy with energy dispersive X-ray spectroscopy allowed the visualization of apatite-like structures upon 7 days of immersion in simulated body fluid. BBG-Ca generated surface structures with a Ca/P ratio ≈1.67, while the surface of the BBG-Sr was populated with structures with a Sr/P ratio ≈1.7. Moreover, bacterial tests showed that the BBG-Mg and BBG-Sr glasses (at concentrations of 9, 18, 36, and 72 mg/mL) present antibacterial characteristics. In particular, BBG-Sr, at concentrations of 9 mg/mL, exhibited bacteriostatic activity against Pseudomonas aeruginosa, and at concentrations ≥18 mg/mL it was able to eradicate this bacterium. These results evidence an antibacterial activity dependent on the BBGs composition, concentration, and bacterial species. Cellular studies showed that the developed BBGs do not present a statistically significant cytotoxic effect against Saos-2 cells after 3 days of culture, showing better performance (in the cases of BBG-Ca and BBG-Sr) than commercial 45S5 Bioglass up to 7 days of culture. Overall, this study demonstrates that BBGs can be effectively designed to combine bioactivity and intrinsic antibacterial activity targeting bone tissue engineering applications. © 2016 American Chemical Society.

Vaquero R.M.M.,Leibniz University of Hanover | Agibetov A.,CNR Institute for Applied Mathematics and Information Technologies | Rzepecki J.,Leibniz University of Hanover | Ondresik M.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | And 10 more authors.
Proceedings of the International Conference on Information Visualisation | Year: 2015

The exploration of biomedical data which involves heterogeneous sources coming from different spatial scales and medical domains is a challenging topic in current research. In this work, we combine efforts regarding multi-scale visualization, multimodal interaction and knowledge formalization for the exploration of multi-scale biomedical data. The knowledge formalization stores and organizes the information sources, the integrated visualization captures all relevant information for the domain expertise of the user and the multimodal interaction provides a natural exploration. We present a concrete example of use of the proposed exploratory system designed for a biologist investigating multi-scale pathologies. © 2015 IEEE.

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