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

Arthroscopic Anatomical Acromioclavicular Joint Reconstruction using a Button Device and a Semitendinosus Graft

Objective: To report a new technique for anatomical acromioclavicular (AC) joint reconstruction. Methods: In order to minimize such complications, the authors describe a new anatomical and biological AC joint repair. This technique aims to provide greater stability by using two anatomically placed clavicular tunnels and a combined construct with a double endobutton cortical fixation for primary stabilization, and to be biologically advantageous by using an autologous semitendinosus (ST) tendon graft. Additionally, the coracoclavicular ligament reconstruction is complemented with an AC joint cerclage and capsular reinforcement, which will protect the biological construction in its initial stage of healing. Results: This technique provides adequate primary and secondary biomechanical stability by passing both a semitendinosus autogenous graft and a double endobutton device, through anatomically placed and small diameter clavicle holes, without the need for coracoid drilling. Our technique showed encouraging results regarding pain resolution, range of motion, and function. At final follow-up we experienced excellent results with average pain score of 1.6, and average ROM of 159° of forward flexion, 160° of abduction, 68° of external rotation, and internal rotation level at T11. Postoperative function also showed great improvements with average ASES of 85 points, an average Constant Score of 87 and a Subjective Shoulder Value of 89 points. This technique also achieved perfectly acceptable radiographic results, with an average coracoclavicular distance increase of 0.8 mm. Regarding complications, our sample showed one case of AC join subluxation, two cases of internal saphenous nerve injury, and two partial graft tears at the suture-button interface, with none of these requiring surgical revision. Conclusion: This technique is advantageous in treatment of acromioclavicular joint dislocation and can be performed in both the subacute and chronic setting.info:eu-repo/semantics/publishedVersio