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Monteiro L.S.,Instituto Superior Of Ciencias Da Saude Norte | Antunes L.,Portuguese Institute of Oncology IPO Porto | Bento M.J.,Portuguese Institute of Oncology IPO Porto | Warnakulasuriya S.,King's College London
Journal of Oral Pathology and Medicine | Year: 2013

Objectives: To analyse the trends and patterns of lip, oral and oro-pharyngeal cancer incidence in Portugal between 1998 and 2007. Patients and Methods: Data on lip, oral and oro-pharyngeal cancers was collected from the databases maintained at the three main Regional Cancer Registries of Portugal (1998-2007). The data were analysed by gender, age and by site. Incidence rates were age standardized by the direct method, and joinpoint regression was used to estimate trends in incidence. Results: During this 10-year period, a total of 9623 cases of lip, oral and oropharynx cancers were reported, 7565 (78.6%) in males and 2058 (21.4%) in females. There was an increase in the age-standardized incidence of oral cancers by 1.96% per year for both sexes grouped together and an increase of 4.34% per year for the female group. Oro-pharyngeal cancer showed an increase incidence trend of 3.49% per year for both sexes grouped together and an increase of 3.49% per year for male group among the sites analysed. Lip cancer showed a decrease in its incidence rate. Conclusion: In view of rising trends, it is necessary to implement policies on oral cancer control by initiating campaigns on oral cancer awareness and screening and to harness political measures on tobacco and alcohol control for the Portuguese population. © 2012 John Wiley & Sons A/S.


das Neves J.,University of Porto | Amiji M.,Northeastern University | Sarmento B.,University of Porto | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology | Year: 2011

Topical microbicides are a promising strategy in the prevention of vaginal and rectal HIV transmission as well as other sexually transmitted pathogens. The perspective of developing nanotechnology-based systems for topical microbicides seems to be useful because important features such as enhanced drug release, targeting, and epithelial penetration can be achieved. However, the interaction of nanoparticles with the mucus fluids that cover the cervicovaginal mucosal epithelium, which can work either as a docking point or as a barrier for diffusion, has been frequently neglected. In this review, we discuss the principles of nanosystems' adhesion to the mucosal tissue and how this relates to the development of optimized microbicide formulations. © 2011 John Wiley & Sons, Inc.


Gomes M.J.,Institute Engineering Biomedica INeB | das Neves J.,Institute Engineering Biomedica INeB | das Neves J.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,Institute Engineering Biomedica INeB | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte
International Journal of Nanomedicine | Year: 2014

Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood-brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretro-viral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood-brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS. © 2014 Gomes et al.


Castro S.I.,Instituto Superior Of Ciencias Da Saude Norte | Rocha J.C.,Instituto Superior Of Ciencias Da Saude Norte
Journal of Loss and Trauma | Year: 2013

The connections between complicated grief and traumatic stress have previously been investigated; however, the learning effects resulting from previous losses and emotional clarity are still unclear. Understanding these effects may shed more light on the general hypotheses of emotional aging. We aimed to assess the moderating effects of emotional clarity and previous losses on bereavement outcomes. This study evaluated 190 participants with a sociodemographic questionnaire, the Inventory of Complicated Grief, the Impact of Event Scale-Revised, and the Difficulties in Emotion Regulation Scale. The results confirm that previous losses change the relationship between complicated grief and trauma and that emotional clarity changes the association between previous losses and complicated grief. © 2013 Copyright Taylor and Francis Group, LLC.


Antunes F.,University of Porto | Andrade F.,University of Porto | Araujo F.,Instituto Superior Of Ciencias Da Saude Norte | Ferreira D.,University of Porto | And 2 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2013

In vitro cell culture models for studying oral drug absorption during early stages of drug development have become a useful tool in drug discovery and development, with respect to substance throughput and reproducibility. The aim of this study was to establish an in vitro cellular model based on human colon carcinoma Caco-2, mucus-producing HT29, and Raji B cells in order to design a model that more accurately mimics the small intestinal epithelial layer. Normal oriented model was set up by seeding co-cultures of Caco-2 and HT29 cells into Transwell filters and maintained under identical conditions following addition of Raji B to the basolateral chamber. Inverted model was set up seeding Caco-2 and HT29 cells on the basolateral chamber and then transferred in the Transwell device with the epithelial cells facing the basolateral chamber following Raji B addition to the apical compartment. Morphological differences on size and thickness of cell membranes were detected between the models studied by using fluorescence microscopy. On the triple co-culture models, cell membranes were increasing in size and thickness from the Caco-2 to Caco-2/HT29 and Caco-2/Raji B. Also, the nuclei seem to be larger than in the other studied models. Insulin permeation was higher on the triple co-culture model when compared to the Caco-2/HT29 co-culture model. Also, insulin permeation as mediated by nanoparticles and insulin solution permeation was higher on the normal oriented Caco-2/HT29/Raji B model as compared to the inverted model. Overall, our results suggest that Caco-2/HT29/Raji B triple co-culture normal oriented cellular model may be reliable to obtain a more physiological, functional, and reproducible in vitro model of the intestinal barrier to study protein absorption, both in solution and when delivered by nanocarriers. © 2012 Elsevier B.V. All rights reserved.


Fonte P.,Instituto Superior Of Ciencias Da Saude Norte
Biomatter | Year: 2012

PLGA nanoparticles are useful to protect and deliver proteins in a localized or targeted manner, with a long-term systemic delivery pattern intended to last for a period of time, depending on polymer bioerosion and biodegradability. However, the principal concern regarding these carriers is the hydrolytic instability of polymer in aqueous suspension. Freeze-drying is a commonly used method to stabilize nanoparticles, and cryoprotectants may be also used, to even increase its physical stability. The aim of the present work was to analyze the influence of cryoprotectants on nanoparticle stability and porosity after freeze-drying, which may influence protein release and stability. It was verified that freeze-drying significantly increased the number of pores on PLGA-NP surface, being more evident when cryoprotectants are added. The presence of pores is important in a lyophilizate to facilitate its reconstitution in water, although this may have consequences to protein release and stability. The release profile of insulin encapsulated into PLGA-NP showed an initial burst in the first 2 h and a sustained release up to 48 h. After nanoparticles freeze-drying the insulin release increased about 18% in the first 2 h due to the formation of pores, maintaining a sustained release during time. After freeze-drying with cryoprotectants, the amount of insulin released was higher for trehalose and lower for sucrose, glucose, fructose and sorbitol comparatively to freeze-dried PLGA-NP with no cryoprotectant added. Besides the porosity, the ability of cryoprotectants to be adsorbed on the nanoparticles surface may also play an important role on insulin release and stability.


Soares S.,Instituto Superior Of Ciencias Da Saude Norte | Costa A.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte | Sarmento B.,University of Porto
Expert Opinion on Drug Delivery | Year: 2012

Introduction: Insulin has usually been administered subcutaneously in the treatment of diabetes mellitus. Alternative delivery routes of insulin are expected to overcome some limitations, mainly concerned with the possibility of hypoglycemia episodes, weight gain and inadequate post-meal glucose control, in order to lead a better patient compliance. Areas covered: This review article covers all the most relevant non-invasive insulin delivery methods under development, respective technology and clinical data available according to their status of development. Special focus is given to the systems with late clinical trial evidences, their achievements and pitfalls. Pulmonary and oral appear to be the most advantageous routes, with regard to the long list of potentially marketed products. Expert opinion: Alternative insulin delivery to the subcutaneous administration is more and more close to the success, being fundamental that any optimized technology could overcome the overall low mucosal bioavailability of insulin, mostly due to its early degradation before absorption, inactivation and digestion by proteolytic enzymes and poor permeability across mucosal epithelium because of its high molecular weight and lack of lipophilicity. © 2012 Informa UK, Ltd.


Mendes R.A.,University of Porto | Mendes R.A.,Instituto Superior Of Ciencias Da Saude Norte | Carvalho J.F.,University of Porto | Waal I.v.d.,VU University Amsterdam
Oral Oncology | Year: 2010

In the classification of Head and Neck Tumors, published in 2005 by the World Health Organization Classification, the odontogenic keratocyst has been reclassified as a benign intraosseous neoplasm, calling it "keratocystic odontogenic tumor" (KCOT). Significant differences on the molecular level between KCOT and other odontogenic cystic lesions suggest a different biological origin. Genetic and molecular research regarding odontogenic tumors, and KCOTs in particular, has led to an increasing amount of knowledge and understanding of their physiopathological pathways. A review of the biological behavior of this recognized aggressive pathological entity of the jaws and a contemporary outline of the molecular (growth factors, p53, PCNA and Ki-67, bcl-2) and genetic (PTCH, SHH) alterations associated with this odontogenic neoplasm provides a better understanding of the mechanisms involved in its development and strengthen the current concept that the KCOT should, indeed, be regarded as a neoplasm. Furthermore, markers known to be rapidly induced in response to growth factors, tumor promoters, cytokines, bacterial endotoxins, oncogenes, hormones and shear stress, such as COX-2, may also shed new light on the biological mechanisms involved in the development of these benign but sometimes aggressive neoplasms of the jaws. © 2009 Elsevier Ltd. All rights reserved.


Antunes F.,University of Porto | Andrade F.,University of Porto | Ferreira D.,University of Porto | Nielsen H.M.,Copenhagen University | And 2 more authors.
Current Drug Metabolism | Year: 2013

Prediction of human intestinal absorption is a major goal in the design, optimization, and selection of drugs intended for oral delivery, in particular proteins, which possess intrinsic poor transport across intestinal epithelium. There are various techniques currently employed to evaluate the extension of protein absorption in the different phases of drug discovery and development. Screening protocols to evaluate protein absorption include a range of preclinical methodologies like in silico, in vitro, in situ, ex vivo and in vivo. It is the careful and critical use of these techniques that can help to identify drug candidates, which most probably will be well absorbed from the human intestinal tract. It is well recognized that the human intestinal permeability cannot be accurately predicted based on a single preclinical method. However, the present social and scientific concerns about the animal well care as well as the pharmaceutical industries need for rapid, cheap and reliable models predicting bioavailability give reasons for using methods providing an appropriate correlation between results of in vivo and in vitro drug absorption. The aim of this review is to describe and compare in silico, in vitro, in situ, ex vivo and in vivo methods used to predict human intestinal absorption, giving a special attention to the intestinal absorption of therapeutic peptides and proteins. © 2013 Bentham Science Publishers.


Martins S.M.,University of Porto | Martins S.M.,University of Southern Denmark | Sarmento B.,University of Porto | Sarmento B.,Instituto Superior Of Ciencias Da Saude Norte | And 4 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2013

This study intended to investigate the ability of solid lipid nanoparticles (SLN) to deliver camptothecin into the brain parenchyma after crossing the blood-brain barrier. For that purpose, camptothecin-loaded SLN with mean size below 200 nm, low polydispersity index (<0.25), negative surface charge (-20 mV), and high camptothecin association efficiency (>94%) were produced. Synchrotron small and wide angle X-ray scattering (SAXS/WAXS) analysis indicates that SLN maintain their physical stability in contact with DMPC membrane, whereas SLN change the lamellar structure of DMPC into a cubic phase, which is associated with efficient release of the incorporated drugs. Cytotoxicity studies against glioma and macrophage human cell lines revealed that camptothecin-loaded SLN induced cell death with the lowest maximal inhibitory concentration (IC50) values, revealing higher antitumour activity of camptothecin-loaded SLN against gliomas. Furthermore, in vivo biodistribution studies of intravenous camptothecin-loaded SLN performed in rats proved the positive role of SLN on the brain targeting since significant higher brain accumulation of camptothecin was observed, compared to non-encapsulated drug. Pharmacokinetic studies further demonstrated lower deposition of camptothecin in peripheral organs, when encapsulated into SLN, with consequent decrease in potential side toxicological effects. These results confirmed the potential of camptothecin-loaded SLN for antitumour brain treatments.

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