Development of pH-sensitive polymeric nanoparticles for targeted drug delivery to the ischemic heart

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017Heart failure post-myocardial infarction remains one of the global leading causes of mortality. The therapeutics, available today, only ameliorate the symptoms, without having any preventive effect on the, functional and structural, heart-remodeling process that ensues after such ischemic event. For this, lately, nanotechnology has emerged as a possible alternative to overcome countless limitations of conventional cardiovascular medicine. The present study focus on the preparation of nanoparticles with resort to the emulsification and solvent evaporation method, using the spermine-modified acetalated dextran as polymer for selective drug delivery of a cardioprotective drug. Additionally, it dwells on the subsequent functionalization resorting to crosslinking chemistry and using propylene glycol as a bioconjugate, given its hydrophilic properties and ability to prolong the nanoparticles’ plasma half-life. The process and formulation variables, explored in this investigation, whether on preparation or functionalization, revealed to be of crucial importance to the nanosystem’s characteristics. The optimization, on propylene glycol conjugation, was not possible, for the drug-loaded nanoparticles, within the time frame set for the experimental work. Upon PEGylation, major improvements were verified in colloidal stability (assessed in cell culture medium) and cytocompatibility (assessed in rat myoblasts). The drug release did not follow the pH-sensitive solubility pattern of the polymer, that is, with burst release in acidic conditions and sustained release in neutral pH. Several points to take in consideration and suggestions, for future work, are presented on how to refine this platform for intracellular nanodelivery.Uma das principais causas de mortalidade, a nível global, continua a ser insuficiência cardíaca pós-enfarte do miocárdio. As terapêuticas atualmente disponíveis apenas atenuam os sintomas, sem qualquer efeito de prevenção no processo de remodelação cardíaca, funcional e estrutural, que se inicia após o episódio de isquemia. Por isto, a nanotecnologia tem, ultimamente, emergido como uma possível alternativa para superar as inúmeras limitações da terapia cardiovascular convencional. O presente estudo foca-se na preparação de nanopartículas recorrendo ao método de emulsificação e evaporação do solvente, utilizando como polímero dextrano modificado com grupos acetais e espermina para a veiculação seletiva de um fármaco cardio-protetor. Adicionalmente, incide na posterior funcionalização recorrendo a química de reticulação e utilizando como biconjugado o propilenoglicol, atendendo às suas propriedades hidrofílicas e capacidade de prolongar a semivida das nanopartículas no plasma. As variáveis de processo e formulação, exploradas nesta investigação, quer na preparação quer na funcionalização, revelaram ter uma importância crucial nas características do nano-sistema. A otimização da conjugação com propilenoglicol não foi possível para as nanopartículas com fármaco, dentro da janela temporal concebida para o trabalho experimental. Após a peguilação, foram verificadas claras melhorias na estabilidade coloidal (avaliada em meio de cultura) e citocompatibilidade (avaliada em mioblastos de rato). A libertação do fármaco não seguiu o padrão da solubilidade do polímero, sensível ao pH, isto é, com libertação imediata em condições ácidas e libertação retardada a pH neutro. Diversas considerações a ter em conta e sugestões, para futuros trabalhos, são apresentadas no sentido de aperfeiçoar esta plataforma de nano-veiculação intracelular

APLICAÇÕES DA EXTRAFISCALIDADE NO DIREITO BRASILEIRO

O presente trabalho tem por objetivo analisar a extrafiscalidade no âmbito da sua aplicação. Quando a instituição de uma espécie tributária ocorre com um propósito que vai além do meramente arrecadatório, diz-se que tais espécies são dotadas, além da fiscalidade, de um viés extrafiscal. O emprego das normas tributárias com o objetivo de induzir comportamentos intersubjetivos e influir nas tomadas de decisões torna a ordem econômica verdadeiro suporte para realização de políticas públicas. Palavras-chave: Extrafiscalidade. Tributação. Intervenção. Política fiscal. Efetividade

Failure of the Embankment on Soft Soil in Recife-Brazil

This paper presents the study of the rupture of an embankment on soft clay, localized in Recife, Brazil. The data was obtained from partnership of the Department of Civil Engineering of the Federal University of Pernambuco, Brazil and the company Gusmão Engineers Associates, which it was possible to perform a Master Thesis. The embankment was constructed without geotechnical investigation project, accompaniment and technological control. After the rupture, to understand the process, a geotechnical investigation was performed to permit a total stress stability analyze / back-analyze, considering circular and non-circular surfaces, occurrence of cracking in embankment, and the three-dimensional effect. The Data Base of Recife soft clays (Coutinho et al. 1998c) were used to complement the technical information necessary to the study. In the evaluation of the undrained shear strength of the foundation (Su) was used the results of field vane test, with consideration of the corrections proposals for Bjerrum (1973). All the results of this work showed that rupture was previsible if adequate geotechnical investigation and stability analysis had been done

Chronic wound assessment: cultural and linguistic adaptation for European Portuguese of RESVECH-2 scale

Introduction: In order to assess and to follow up the evolution of chronic wounds, it is advisable to apply measurement scales. This procedure allows clinicians to verify the appropriateness of their activities and whether the healing process is evolving as expected. Aim: To conduct a cross-cultural adaptation and psychometric analysis of Portuguese version of RESVECH 2.0. Methods: A quantitative and correlational study was designed and, to perform the cross-cultural adaptation of RESVECH 2.0, we followed the classic sequential approach for linguistic equivalence to European Portuguese. The study occurred at a Portuguese oncology hospital and the sample encompassed 281 patients with multiple chronic wounds. Results: RESVECH 2.0 is a practical measurement instrument, easy to use, and well accepted by nurses to know all kinds of wounds’ etiologies. The reliability test revealed an acceptable internal consistency and high proportion of agreement between two raters assessing the same patient. Construct validity was considered average/good and the principal component factor analysis with varimax rotation obtained six factors corresponding to 59.5% of explained variance. When comparing the domains from RESVECH 2.0 with those from BWAT we found statistically significant correlations. Conclusion: The adapted version of RESVECH 2.0 scale presents a good internal consistency and is valid for the Portuguese language and culture, being useful and effective in clinical practice.N/

A neural network underlying cognitive strategies related to eating, weight and body image concerns

Concerns about food intake, weight and body shape can trigger negatively loaded emotions, which may prompt the use of cognitive strategies to regulate these emotional states. A novel fMRI task was developed to assess the neurobehavioral correlates of cognitive strategies related to eating, weight and body image concerns, such as self-criticism, avoidance, rumination, and self-reassurance. Fourteen healthy females were presented audio sentences referring to these conditions and instructed to repeat these internally while engaging their thoughts with the content of food or body images. Participants were asked to report the elicited emotion and rate their performance. All cognitive strategies recruited a network including the inferior and superior frontal gyri, orbitofrontal and anterior cingulate cortex, insula, and dorsal striatum. These brain regions are involved in emotional, reward and inhibitory control processing. Representational similarity analysis revealed distinct patterns of neural responses for each cognitive strategy. Additionally, self-report measures showed that self-criticism was positively associated with superior frontal gyrus (SFG) activation. Self-compassion scores were negatively correlated with activations in the insula and right putamen, while self-reassurance scores were negatively associated with activity in the orbitofrontal cortex. These findings identify a neural network underlying cognitive strategies related to eating, weight and body image concerns, where neurobehavioral correlation patterns depend on the cognitive strategy

Bioresorbable ureteral stents from natural origin polymers

In this work, stents were produced from natural originpolysaccharides. Alginate, gellan gum, and a blend ofthese with gelatin were used to produce hollow tube (stents)following a combination of templated gelation and criticalpoint carbon dioxide drying. Morphological analysis of thesurface of the stents was carried out by scanning electronmicroscopy. Indwelling time, encrustation, and stability ofthe stents in artificial urine solution was carried out up to 60days of immersion. In vitro studies carried out with simulatedurine demonstrated that the tubes present a high fluid uptakeability, about 1000%. Despite this, the materials are able tomaintain their shape and do not present an extensive swellingbehavior. The bioresorption profile was observed to behighly dependent on the composition of the stent and it canbe tuned. Complete dissolution of the materials may occurbetween 14 and 60 days. Additionally, no encrustation wasobserved within the tested timeframe. The ability to resistbacterial adherence was evaluated with Gram-positive Staphylococcus aureus and two Gram-negatives Escherichia coliDH5 alpha and Klebsiella oxytoca. For K. oxytoca, no differenceswere observed in comparison with a commercialstent (BiosoftVR duo, Porges), although, for S. aureus alltested compositions had a higher inhibition of bacterialadhesion compared to the commercial stents. In case ofE. coli, the addition of gelatin to the formulations reducedthe bacterial adhesion in a highly significant manner comparedto the commercial stents. The stents produced by thedeveloped technology fulfill the requirements for ureteralstents and will contribute in the development of biocompatible and bioresorbable urinary stents.Contract grant sponsor: the European Union Seventh Framework Programme (FP7/2007-2013); contract grant number: REGPOT-CT2012-316331POLARIS Contract grant sponsor: Novel smart and biomimetic materials for innovative regenerative medicine approaches”; contract grant number: RL1 – ABMR – NORTE-01-0124-FEDER-000016; North Portugal Regional Operational Programme (ON.2 – O Novo Norte), National Strategic Reference Framework (NSRF), European Regional Development Fund (ERDF) Contract grant sponsor: FCT post-doc; contract grant numbers: SFRH/BPD/39333/2007, SFRH/BPD/90533/20

Avaliação de alterações em tomografia computadorizada de tórax de pacientes internados por Covid-19

Introduction: SARS-CoV-2 has rapid dissemination and high infectivity and can evolve into Severe Respiratory Distress Syndrome (SARS), which led to a high number of deaths and hospitalizations in the recent pandemic. Computed tomography (CT) of the chest has demonstrated an essential role in the initial evaluation and evolution of these patients.Methodology: This was a retrospective observational study at a single center, University Hospital in Northeastern Brazil, evaluating 97 patients hospitalized for COVID-19 with laboratory confirmation to evaluate and quantify the chest CTfindings, comparing the findings with the severity of the case and relating them to the morbidities presented. The CT scans were performed by radiologists from the hospital and the data were evaluated by the university’s statistics laboratory.Results: Among the main alterations, ground-glass opacities were present in more than 90% of the patients. The study observed that the magnitude of the pulmonary involvement of this finding had a relationship with the outcome of higher hospitalization. Conclusion: In this sense, the relevance of chest CT to suggest the diagnosis of Covid-19 and establish the prognosis of the disease is observed. However, further studies are still needed to confirm these findings.Introdução: O SARS-CoV-2 possui rápida disseminação e alta infectividade, podendo evoluir com Síndrome da Angústia Respiratória Grave (SARS), o que levou a um número elevado de mortes e internações na recente pandemia. A Tomografia Computadorizada (TC) de tórax demonstrou um papel essencial na avaliação inicial e evolução dessespacientes. Metodologia: Este foi um estudo observacional retrospectivo em centro único - Hospital Universitário no Nordeste do Brasil - avaliando 97 pacientes internados por COVID-19 com confirmação laboratorial, a fim de avaliar e quantificar os achados de TC de tórax, comparando os achados com a gravidade do caso e relacionando-os com as morbidades apresentadas. As TCs foram laudadas por radiologistas do próprio hospital. Após isso, os dados foram avaliados pelo laboratório de estatística da universidade para serem analisados e discutidos. Resultados: Dentre as principais alterações, o vidro fosco estava presente em mais de 90% dos pacientes. Foi observado que a magnitudedo comprometimento pulmonar deste achado apresentou relação desfavorável com o desfecho da internação. Conclusão: Neste sentido, observa-se a relevância da TC de tórax para sugerir o diagnóstico de Covid-19 e estabelecer o prognóstico da doença. No entanto, ainda são necessários mais estudos para destrinchar estes achados

Uso de destiladores de mao con solubles en pollos de engorde

            This study aimed to evaluate the inclusion of distiller's dried grains with soluble (DDGS) of corn in the broiler diet on growth performance, carcass and viscera yield, and biometrics of the gastrointestinal tract. In total, 700 male Cobb 500 broilers were distributed in a completely randomized design with five treatments, seven replicates, and 20 chicks per experimental unit. The treatments consisted of a control and four levels of inclusion of DDGS (4, 8, 12, and 16%) in the diet. The inclusion of the DDGS did not influence the performance in the periods of 1 to 7 and 36 to 42 days of age. For broilers 8 to 35 days old, the feed intake was not altered by the treatments, but the average weight gain and feed conversion (p<0.05) had a quadratic polynomial effect. There was a reduction in carcass and breast weight of broilers slaughtered at 42 days of age fed with 12 and 16% DDGS. The DDGS in diets can be considered an alternative ingredient in diets for broilers up to 12% inclusion.El estudio tuvo como objetivo evaluar la inclusión de granos secos de maíz de destilería con solubles (DDGS) en la dieta de pollos de engorde sobre el rendimiento del crecimiento, la canal y las vísceras, y la biometría del tracto gastrointestinal. En total, se distribuyeron 700 pollos de engorde Cobb 500 machos en un diseño completamente al azar con cinco tratamientos, siete repeticiones y 20 pollos por unidad experimental. Los tratamientos consistieron en un control y cuatro niveles de inclusión de DDGS (4, 8, 12 y 16%) en la dieta. La inclusión de los DDGS no influyó en el rendimiento en los periodos de 1 a 7 y 36 a 42 días de edad. Para pollos de engorde de 8 a 35 días de edad, el consumo de alimento no fue alterado por los tratamientos, pero la ganancia de peso promedio y la conversión alimenticia (p<0.05) tuvieron un efecto polinomial cuadrático. Hubo una reducción en el peso de la canal y de la pechuga de los pollos de engorde sacrificados a los 42 días de edad alimentados con 12 y 16% de DDGS. Los DDGS en dietas pueden considerarse un ingrediente alternativo en dietas para pollos de engorde hasta un 12% de inclusión

Timed up and go test and self-perceived health in elderly: population-based study

Due to the aging process, chronic diseases arise with increased use of medications and there is a need to evaluate the elderly to prevent functional dependence and falls. The aim of this study was to compare gender, sociodemographic characteristics, fall occurrences, self-reported diseases, quantity of drugs with timed up and go test (TUG) and TUG-cognitive, and to associate these factors with the self-perception of health of the elderly in the community. Were selected 513 elderly people, with 384 that completed the TUG test to evaluate the functional capacity. There was difference between the female and male, in the variables: age-group 70 to 79 years (p=0.036) ≥ 80 years (p=0.013); per capita income in the female ≤ 1 minimum wage (p=0.005) and >2 (p=0.013), falls (p=0.001), systemic hypertension (p<0.001), arthritis or rheumatism (p=0.033), depression (p=0.048), osteoporosis (p<0.001), medications 3 to 4 (p=0.008), self-perceived health (p=0.030) and in the TUG (p<0.001) and TUG-cognitive (p=0.002). The prevalence by Poisson regression Robust (RPa), the variables associated with health self-perceived: heart disease (p=0,047), stroke (p=<0,001), osteoporosis (p=0,013) and TUG motor (p=0,028). Women had more health problems, weakness and poor physical performance, indicating the need for special attention as the aging aspects. So, TUG test can be useful tool for risk evaluate of falls in the elderly living in the community

Atuação de enfermeiras para inserção do homem na Estratégia de Saúde da Família

This study aimed to analyze the role of nurses in including men in the Family Health Strategy in Icó, Ceará. This exploratory, descriptive, qualitative research was conducted with eight nurses working in Family Health Strategy teams in the urban área of Icó, Ceará, Brazil, from August to September 2018 through semi-structured interviews. After collection, transcription, and organization, data were analyzed following Minayo’s Thematic Content Analysis technique. The research followed the recommendations of Resolution N° 466/12. Similar contents can be grouped from the analysis of the information in the statements, giving rise to four categories: Category I – Nurses’ (lack of) knowledge about PNAISH. In this category, we can observe that the nurses had little knowledge of PNAISH, hampering the provision of men’s healthcare; Category II – Invisible men: Difficulties faced by nurses When working on men’s health in the ESF. It was evident that men’s resistance and opening hours were the main difficulties; Category III – Strategies used by nurses to promote men’s health. We identified that nurses’ main focus was Blue November; Category IV – Lack of continuing men’s health training. We found that the nurses never participated in anything related to men’s health. Conclusion: Therefore, it is necessary to perform continuing education and professional training to improve men’s healthcare.Este estudo objetiva analisar a atuação de enfermeiras para inserção do homem na Estratégia de Saúde da Família do município de Icó, Ceará. Uma pesquisa exploratória, descritiva de natureza qualitativa, foi realizada com oito enfermeiras atuantes em equipes da Estratégia de Saúde da Família da zona urbana da cidade de Icó, Ceará. A pesquisa foi realizada nos meses de agosto e setembro de 2018, por entrevistas semiestruturadas. Após a coleta, transcrição e organização, realizou-se a análise dos dados, sendo seguida a técnica de Análise de Conteúdo Temática proposta por Minayo. A pesquisa seguiu as recomendações da Resolução No 466/12. A partir da análise das informações continas nas falas, pode-se agrupar os conteúdos similares, os quais deram origem a quatro categorias: Categoria I – O (des)conhecimento de enfermeiras sobre a PNAISH. Pode-se observar que as enfermeiras tinham pouco conhecimento da PNAISH, o que pode dificultar na assistência à saúde do homem; Categoria II – Homens Invisíveis: Dificuldades enfrentadas pelas enfermeiras para trabalhar a saúde do homem na ESF. Evidenciou-se que resistência dos homens e o horário de atendimento são as principais dificuldades encontradas. Categoria III – Estratégias utilizadas pelas enfermeiras para promoção da saúde masculina. Identificou-se que as enfermeiras têm como foco principal o novembro azul. Categoria IV – Ausência de capacitação continuada relacionado à saúde do homem. Constatou-se que as enfermeiras nunca participaram de algo relacionado à saúde masculina. Faz-se necessária a realização de educação permanente e capacitação continuada dos profissionais para melhorar a assistência voltada à saúde masculina