Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone

The aim of the present work was to develop and characterize two different nanosystems, nanospheres and nanocapsules, containing either xanthone (XAN) or 3-methoxyxanthone (3-MeOXAN), with the final goal of improving the delivery of these poorly water-soluble compounds. The xanthones-loaded nanospheres (nanomatrix systems) and nanocapsules (nanoreservoir systems), made of poly(DL-lactide-co-glycolide) (PLGA), were prepared by the solvent displacement technique. The following characteristics of nanoparticle formulations were determined: particle size and morphology, zeta potential, incorporation efficiency, thermal behaviour, in vitro release profiles and physical stability at 4 degrees C. The nanospheres had a mean diameter 77%) were higher than those corresponding to nanospheres for both xanthones. The release of 3-MeOXAN from nanocapsules was similar to that observed for the correspondent nanoemulsion, indicating that drug release is mainly governed by its partition between the oil core and the external aqueous medium. In contrast, the release of XAN from nanocapsules was significantly slower than from the nanoemulsion, a behaviour that suggests an interaction of the drug with the polymer. Nanocapsule formulations exhibited good physical stability at 4 degrees C during a 4-month period for XAN and during a 3-month period for 3-MeOXAN

Nova Abordagem ao Diagnóstico da Sindroma de Alport: Pesquisa da Cadeia α5 do Colagénio Tipo IV na Pele

Em 2000, os autores iniciaram no Serviço de Nefrologia do Hospital de Curry Cabral, um protocolo de avaliação do papel do estudo imunopatológico da biópsia cutânea no diagnóstico da Sindroma de Alport (SA). A SA é uma doença hereditária, secundária a um defeito do colagénio tipo IV (col. IV), principal componente das membranas basais. O col. IV é constituído por 6 cadeias distintas (α1 a α6). A cadeia α5 está presente nas membranas basais glomerulares e da epiderme (MBE). Em cerca de 85% dos casos de SA (forma de transmissão ligada ao cromossoma X) verifica-se uma alteração da cadeia α5, com consequente ausência ou intermitência desta cadeia, na MBE. O objectivo deste trabalho foi pesquisar a presença da cadeia α5 do col. IV na MBE, e consequentemente avaliar o papel da biópsia cutânea no diagnóstico da SA. Para o efeito estudámos as biópsias cutâneas de dezanove indivíduos pertencentes a seis famílias distintas. Em cada uma das famílias havia pelo menos um indivíduo com história de SA. As biópsias cutâneas foram avaliadas por método de imunofluorescência indirecta, com antisoros dirigidos às cadeias α1, α3 e α5 do col. IV. No padrão normal há a presença das cadeias α5 e α1 e ausência de α3 na MBE.Verificou-se a ausência de α5 na MBE em quatro homens com SA enquanto que um caso de SA apresentou um padrão positivo. Nas mulheres com SA verificámos a intermitência da α5. Nas sintomáticas, mas sem doença, obtivémos um padrão de intermitência da α5 em três casos e um padrão positivo em três casos. Nas três mulheres assintomáticas, os padrões foram igualmente positivos. Em todos os espécimes biópticos verificou-se a presença de α1 (controlo positivo) e a ausência de α3 (controlo negativo). Realçamos o valor da biópsia cutânea no diagnóstico da SA. Este método é particularmente relevante no homem, onde a ausência da α5 na MBE determina o diagnóstico da SA com forma de transmissão ligada ao cromossoma X. Nas mulheres verificam-se dois padrões possíveis, positivo ou intermitente. A intermitência estará relacionada com a presença de SA ou estado portador. Assim consideramos que a biópsia cutânea deverá ser o primeiro passo na marcha diagnóstica para a SA em qualquer doente em que se suspeite desta patologia

Multi-heme Cytochromes in Shewanella oneidensis MR-1:Structures, functions and opportunities

Multi-heme cytochromes are employed by a range of microorganisms to transport electrons over distances of up to tens of nanometers. Perhaps the most spectacular utilization of these proteins is in the reduction of extracellular solid substrates, including electrodes and insoluble mineral oxides of Fe(III) and Mn(III/IV), by species of Shewanella and Geobacter. However, multi-heme cytochromes are found in numerous and phylogenetically diverse prokaryotes where they participate in electron transfer and redox catalysis that contributes to biogeochemical cycling of N, S and Fe on the global scale. These properties of multi-heme cytochromes have attracted much interest and contributed to advances in bioenergy applications and bioremediation of contaminated soils. Looking forward there are opportunities to engage multi-heme cytochromes for biological photovoltaic cells, microbial electrosynthesis and developing bespoke molecular devices. As a consequence it is timely to review our present understanding of these proteins and we do this here with a focus on the multitude of functionally diverse multi-heme cytochromes in Shewanella oneidensis MR-1. We draw on findings from experimental and computational approaches which ideally complement each other in the study of these systems: computational methods can interpret experimentally determined properties in terms of molecular structure to cast light on the relation between structure and function. We show how this synergy has contributed to our understanding of multi-heme cytochromes and can be expected to continue to do so for greater insight into natural processes and their informed exploitation in biotechnologies

Prognosis following acute coronary syndromes according to prior coronary artery bypass grafting: Meta-analysis

PURPOSE: Conduct a meta-analysis to study the prognostic influence of a previous coronary artery bypass grafting (CABG) in patients admitted for an acute coronary syndrome (ACS). METHODS: A systematic review of the literature was performed using electronic reference databases through January 2013 (MEDLINE, Cochrane Library, Web of Knowledge, Google Scholar and references cited in other studies). Studies in which ACS outcomes with a previous history of CABG were compared with ACS outcomes with no history of previous CABG were considered for inclusion. The main endpoints of interest were mortality and non-fatal acute myocardial infarction. Data was aggregated at three follow-up times using random-effects meta-analysis models. RESULTS: Twenty-four studies were included which provided 387,181 patients for analysis. Previous CABG ACS patients were older, more diabetic and had a more frequent history of a previous myocardial infarction. Pooled in-hospital mortality was higher for the previous CABG ACS patients (OR 1.22 [1.04-1.44], p<0.01, I(2) 88%). The pooled adjusted OR showed no significant differences for the two groups (adjusted OR 1.13 [0.93-1.37], p=0.22, I(2) 92%). Previous CABG ACS patient had a higher pooled 30-day mortality (OR 1.28 [1.05-1.55], p=0.02, I(2) 74%); a higher non-adjusted (OR 1.61 [1.38-1.88], p<0.01, I(2) 70%) and adjusted (adjusted OR 1.37 [1.15-1.65], p<0.01, I(2) 0%) long-term mortality. Both the in-hospital and the long-term re-infarction rates were higher for the previous CABG ACS patients. CONCLUSIONS: According to our data, ACS patients with previous CABG history had a higher risk for short- and long-term adverse events

Prevalence and duration of breast milk feeding in very preterm infants: A 3-year follow-up study and a systematic literature review

Background: The World Health Organization recommends exclusive breast milk feeding until 6 months and continuing up to 2 years of age; little is known about whether very preterm infants are fed in accordance with these recommendations. We aimed to describe the prevalence and duration of breast milk feeding in very preterm children and to systematically review internationally published data. Methods: We evaluated breast milk feeding initiation and duration in very preterm children born in 2 Portuguese regions (2011‐2012) enrolled in the EPICE cohort and followed‐up to the age of 3 (n = 466). We searched PubMed® from inception to January 2017 to identify original studies reporting the prevalence and/or duration of breast milk feeding in very preterm children. Results: 91.0% of children received some breast milk feeding and 65.3% were exclusively breast fed with a median duration of 2 months for exclusive and 3 months for any breast milk; only 9.9% received exclusive breast milk for at least 6 months, 10.2% received any breast milk for 12 months or more, and 2.0% for up to 24 months. The literature review identified few studies on feeding after hospital discharge (n = 9); these also reported a low prevalence of exclusive breast milk feeding at 6 months (1.0% to 27.0%) and of any breast milk at 12 months (8.0% to 12.0%). Conclusions: The duration of breast milk feeding among Portuguese very preterm infants was shorter than recommended. However, this appears to be common globally. Research is needed to inform strategies to promote continued breast milk feeding.This study was funded by the European Union Seventh Framework Programme (FP7/2007‐2013) under grant agreement no. 259882. This study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI‐01‐0145‐FEDER‐006862; Ref.UID/DTP/04750/2013); the PhD Grant SFRH/BD/111794/2015 (Carina Rodrigues) and the individual grant SFRH/BSAB/113778/2015 (Henrique Barros), co‐funded by the FCT and the POCH/FSE Program

Screening of Dementia in Portuguese Primary Care: Methodology, Assessment Tools, and Main Results

The objectives of this article are as follows: (1) to describe the assessment protocol used to outline people with probable dementia in Primary Health Care; (2) to show the methodological design and procedure to obtain a representative sample of patients with probable dementia; and (3) to report the main characteristics of the sample collected in the context of the study “Characteristics and needs of people with probable dementia.” The study protocol was based on the “Community Assessment of Risk and Treatment Strategies (CARTS) Program” and is composed by a set of instruments that allow the assessment of older adults with probable dementia in several areas (health, psychological, functionality, and other). Descriptive analysis was used to characterize the final sample (n = 436). The study protocol as well as the methodological procedure to obtain the referral of research participants and data collection on the condition of people with probable dementia in Primary Health Care proved to be a valuable tool to obtain a sample of patients distributed by the full range of probable dementia in a large geographical area. Results may allocate the design of care pathways for old people with cognitive disorders to prevent, delay impairment, and/or optimize quality of life of patients