Representações sociais de adultos jovens que vivenciam a doença aterosclerótica coronariana

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-graduação em EnfermagemDentre as doenças cardiovasculares a que vem se destacando como um dos problemas mais preocupantes é a Doença Aterosclerótica Coronariana, pois além de ser uma das principais causas de morte e de incapacidade no Brasil, determina um impacto sócio-econômico de grande magnitude. Esta doença tem sido descrita como a maior epidemia já enfrentada pelo homem moderno. Este estudo objetivou compreender como os adultos jovens com Doença Aterosclerótica Coronariana (DAC), atendidos em um hospital de referência em cardiologia, vêem, sentem e vivenciam a realidade de sua condição de saúde. O caminho teórico-metodológico fundamentou-se na Teoria das Representações Sociais, proposta por Serge Moscovici. Para chegar na compreensão das representações sociais foram realizadas dez entrevistas semi-estruturadas, sendo nove participantes do sexo masculino e uma do sexo feminino, com idade variando entre 34 e 43 anos e o tempo de convivência dessas pessoas com a DAC foi de no mínimo oito meses e no máximo dois anos e quatro meses. A análise dos dados foi efetuada a partir da Análise de Conteúdo proposta por Bardin, permitindo compreender que a DAC provoca importantes mudanças na vida das pessoas, identificadas através de duas categorias que emergiram dos discursos dos sujeitos. A primeira categoria denominada de "A Realidade do Medo" identificou como subcategorias: o medo da dor, o medo da morte, o medo frente ao futuro da família e o medo da incapacidade profissional. A segunda categoria foi entendida como: "A Realidade Social: buscando apoio social" e abrange três subcategorias: o suporte familiar, o suporte religioso e o suporte dos profissionais da saúde. A DAC foi representada pelos adultos jovens como uma doença que os incapacita no apogeu de sua vida produtiva, gerando sentimentos de medo, ansiedade e insegurança, sinalizando sua vulnerabilidade e finitude. Essa realidade é incorporada no universo consensual e se manifesta como uma ameaça que impõem restrições no processo de viver, refletindo em mudanças no âmbito familiar, profissional e social. Para os sujeitos desta pesquisa o apoio social que recebem foi representado como a peça fundamental na construção e manutenção da saúde, sendo manifestada consensualmente por ter como função básica a segurança e a proteção. A compreensão das representações sociais de adultos jovens no processo de viver com a DAC permitiu o reconhecimento dos sentimentos aflorados pela doença, seus desejos e significados, o que indica a necessidade de repensar a assistência de enfermagem, voltada para a subjetividade das pessoas que vivenciam uma situação de cronicidade. Of all cardiovascular diseases, the coronary atherosclerotic disease (CAD) has become the most concerning, for it is one of the main causes of death and incapacity in Brazil, with great socioeconomic impact. This disease has been described as the biggest epidemic ever faced by modern man. This study had the objective of understanding how young adults with the coronary artery disease, treated at a hospital with excellence in cardiology, see, feel and live the reality of their health condition. The theoretical background and methods followed the Theory of the Social Representations, by Serge Moscovici. To understand their social representations, ten interviews were conducted with nine male participants and one female, with ages between 34 and 43 years, with the diagnosis of DAC made between eight and 28 months before data collection. The data analysis was conducted through Content Analysis, as proposed by Bardin, allowing to understand that the CAD causes great changes in people's lives, identified through two categories that were mentioned in the participant's reports. The first category was referred as "the reality of fear", identified in the following subcategories: the fear of pain, the fear of death, the fear of the future of the family, and the fear of professional incapacity. The second category was named: "the social reality: searching for social support", and it includes three subcategories: the family's support, the religious' support and the support of the health professionals. The young adults in this study described the CAD as a disease that incapacitates them at the top of their productive lives, generating feelings of fear, anxiety and insecurity, showing their vulnerability and sense of finitude. This reality is incorporated in their consensual universe as a threat that imposes restrictions in the process of living, reflecting in changes in their familiar, professional and social scope. For the participants of this study, the social support they received was represented as fundamental in the maintenance and improvement of their health, being revealed as having an important function to the feeling of security and protection. The understanding of the social representations of young adults with CAD allowed the understanding of the feelings derived from the disease, its desires and meanings, which indicate the necessity of rethinking the nursing assistance, directed at the subjective aspects of people who live deeply affected by a chronic situation

MicroRNAs biomarkers for early screening of colorectal cancer

Colorectal cancer (CRC) is the most incident neoplasia in Portugal. When diagnosed early, the 5-year cancer survival rate increases to 90% [2]. However, the current noninvasive screening method for CRC, Fecal Immunochemical Test (FIT), has low sensitivity and specificity for detecting precancerous lesions. Therefore, it is necessary to develop a new screening method for CRC. MicroRNAs (miRs) play a role in genetic events associated with carcinogenesis, and their disrupted expression in tumors can be readily detected in biological fluids [5-8]. This characteristic offers a promising tool for CRC screening. Review the existing literature to assess the advancements made in recent years in the potential use of miRs as a biomarker to improve the CRC screening. A comprehensive literature review was conducted, analyzing a total of 54 studies that investigated miRs expression in stool and blood samples and evaluated is potential as biomarkers for CRC identification. In our search, we identified a total of 104 miRs with potential relevance to CRC screening in both stool and blood samples. Among these miRs, miR-21-5p and miR-92a-3p, along their cluster including miR-29a-3p, miR-20a-5p, and miR-18-5p, emerged as the most frequently mentioned and promising candidates. Furthermore, is reported a differential expression of miR-135b-5p, miR-223-3p, and miR-451 only in stool specimens, while miR-139-3p and miR-4516 exhibit this altered expression in blood samples. Other notable miRs, including miR-146a-5p, miR-199a-5p, miR-421, miR-27a-3p, and miR-221-3p, have shown promising results in detecting advanced adenomas, exhibiting a better performance compared to FIT. However, these findings require further validation in a larger patient cohort and across different biological samples to confirm their significance for CRC and precancerous lesions detection. Therefore, miRs are regarded as a promising approach for enhancing the detection of CRC, particularly in the identification of precancerous lesions. Nevertheless, further studies are required to assess the accuracy of these molecules as biomarkers.info:eu-repo/semantics/publishedVersio

Polymeric versus lipid nanoparticles: comparative study of nanoparticulate systems as indomethacin carriers

Encapsulation of nonsteroidal or non-steroidal anti-inflammatory drugs (NSAID) in nanocarrier systems aims to enhance bioavailability and to decrease toxicity of these drugs and thus improve the efficacy of treatments. With this aim two types of nanoparticles were prepared and compared: lipid nanoparticles, made of cetyl palmitate and Miglyol 812 which were uncoated or coated with chitosan; or polymeric nanoparticles, made of poly (DL-lactic-co-glycolic acid) (PLGA) for which different emulsion stabilizers were also tested (poly (vinyl alcohol) (PVA), and Pluronic F68). Nanoparticles were characterized for drug content and for particle size, charge and morphology. The lipid matrix was analyzed regarding its crystallinity by differential scanning calorimetry (DSC). The size of the nanoparticles was measured by dynamic light scattering (DLS) which indicated a unimodal particle size distribution in all systems. Nanoparticles’ stability was confirmed by their highly negative surface charge in the case of polymeric and uncoated lipid nanoparticles, as analyzed by zeta potential measurements using electrophoretic light scattering (ELS). Lipid chitosan coated nanoparticles have also shown to be stable presenting highly positive surface charge. Results have further demonstrated that indomethacin is highly encapsulated regardless the type of particles. Morphological analysis by scanning electron microscopy has shown that the nanoparticles were smooth and spherical. The results gathered within the current study point to the conclusion that the proposed formulations provide nanoparticles of satisfactory quality to encapsulate indomethacin, which might be used to improve bioavailability of other NSAID in the treatment of inflammation.This work was supported by FEDER through POFC – COMPETE and by national funds from FCT through the projects PEst-C/FIS/UI0607/2013 (CFUM). Marlene Lucio holds a position of Researcher FCT with the reference IF/00498/2012. We acknowledge NanoDelivery-I&D em Bionanotecnologia, Lda for access to their equipment.info:eu-repo/semantics/publishedVersio

Rational development of liposomal hydrogels: A strategy for topical vaginal antiretroviral drug delivery in the context of HIV prevention

HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evaluate the physicochemical characteristics of both drugs, and to study their biophysical impact in lipid model systems. Results from these pre-formulation studies defined hydrogels as adequate vehicles to incorporate TDF-loaded liposomes and FTC. After studying interactions with mucin, zwitterionic liposomes with a mean diameter of 134 ± 13 nm, an encapsulation TDF efficiency of approximately 84%, and a transition temperature of 41 °C were selected. The chosen liposomal formulation was non-cytotoxic to HEC-1-A and CaSki cells, and was able to favor TDF permeation across polysulfone membranes (Jss = 9.9 μg·cm−2·h−1). After the incorporation of TDF-loaded liposomes and FTC in carbomer hydrogels, the drug release profile was sustained over time, reaching around 60% for both drugs within 3–6 h, and best fitting the Weibull model. Moreover, liposomal hydrogels featured pseudoplastic profiles that were deemed suitable for topical application. Overall, the proposed liposomal hydrogels may constitute a promising formulation for the vaginal co-delivery of TDF/FTC.Funding for this work was provided by Fundação para a Ciência e Tecnologia (FCT) in the framework of the Strategic Funding UID/FIS/04650/2019 and in the ambit of the project POCI-01-0145-FEDER-032651 and PTDC/ NAN-MAT/326512017, co-financed by the European Regional Development Fund (ERDF), through COMPETE 2020, under Portugal 2020, and FCT I.P. This work was also supported by the strategic program UID/BIA/04050/2019 and project ERA-IB-2-6/0004/2014 funded by national Portuguese funds through FCT I.P. M. Lúcio thanks FCT and ERDF for doctoral position Ref. CTTI-150/18-CF(1) in the ambit of the project CONCERT (POCI-01-0145-FEDER-032651 and PTDC/NAN-MAT/326512017). This work was further supported by Institute for Research and Innovation in Health Sciences (UID/BIM/04293/2019), by Programa Gilead GÉNESE, Gilead Portugal (refs. PGG/046/2015 and PGG/002/2016), and by CEB (UID/BIO/04469/2019)

CD28 Family and Chronic Rejection: “To Belatacept...and Beyond!”

Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients

Omega-3- and resveratrol-loaded lipid nanosystems for potential use as topical formulations in autoimmune, inflammatory, and cancerous skin diseases

Resveratrol (RSV) and omega 3 (3), because of their biological favorable properties, have become subjects of interest for researchers in dermocosmetic and pharmaceutical industries; however, these bioactives present technological limitations that hinder their effective delivery to the target skin layer. To overcome the stability and skin permeation limitations of free bioactives, this work proposes a combined strategy involving two different lipid nanosystems (liposomes and lipid nanoparticles) that include 3 in their lipid matrix. Additionaly, RSV is only encapsulated in liposomes that provid an adequate amphiphilic environment. Each formulation is thoroughly characterized regarding their physicalchemical properties. Subsequently, the therapeutic performance of the lipid nanosystems is evaluated based on their protective roles against lipid peroxidation, as well as inhibition of cicloxygenase (COX) and nitric oxid (NO) production in the RWA264.7 cell line. Finally, the lipid nanosystems are incorporated in hydrogel to allow their topical administration, then rheology, occlusion, and RSV releasediffusion assays are performed. Lipid nanoparticles provide occlusive effects at the skin surface. Liposomes provide sustained RSV release and their flexibility conferred by edge activator components enhances RSV diffusion, which is required to reach NO production cells and COX cell membrane enzymes. Overall, the inclusion of both lipid nanosystems in the same semisolid base constitutes a promising strategy for autoimmune, inflammatory, and cancerous skin diseases.This research was funded by FCT/MCTES—Foundation for Science and Technology I.P. from the Minister of Science, Technology, and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) by the COMPETE—Programa Operacional Factores de Competitividade (POFC) through the project CONCERT (POCI-01-0145-FEDER-032651 and PTDC/NAN-MAT/326512017) and the Strategic Funding UID/Multi/04546/2019, UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry CIIMAR), and “Contrato-Programa” UIDB/04469/2020 (CF-UM-UP) and UIDB/04050/2020 (CBMA), and UIDB/04469/2020 (CEB), as well as the Research Center of the Portuguese Oncology Institute of Porto (project no. PI86-CI-IPOP-66-2019), and BioTecNorte operation (NORTE-01-0145-FEDER- 000004) funded by the European Regional Development Fund under the scope of Norte 2020 - Programa Operacional Regional do Norte. Marlene Lúcio thanks FCT and ERDF for her doctoral position (CTTI-150/18-CF (1) within the scope of the CONCERT project. Raul Machado acknowledges FCT I.P. for funding within the Scientific Employment Stimulus project (CEECIND/00526/2018).info:eu-repo/semantics/publishedVersio

The versatility of membrane-water partitioning in pharmacokinetic modelling

info:eu-repo/semantics/publishedVersio

Graphene-Based Nanosystems: Versatile Nanotools for Theranostics and Bioremediation

Since its revolutionary discovery in 2004, graphene— a two-dimensional (2D) nanomaterial consisting of single-layer carbon atoms packed in a honeycomb lattice— was thoroughly discussed for a broad variety of applications including quantum physics, nanoelectronics, energy efficiency, and catalysis. Graphene and graphene-based nanomaterials (GBNs) have also captivated the interest of researchers for innovative biomedical applications since the first publication on the use of graphene as a nanocarrier for the delivery of anticancer drugs in 2008. Today, GBNs have evolved into hybrid combinations of graphene and other elements (e.g., drugs or other bioactive compounds, polymers, lipids, and nanoparticles). In the context of developing theranostic (therapeutic + diagnostic) tools, which combine multiple therapies with imaging strategies to track the distribution of therapeutic agents in the body, the multipurpose character of the GBNs hybrid systems has been further explored. Because each therapy and imaging strategy has inherent advantages and disadvantages, a mixture of complementary strategies is interesting as it will result in a synergistic theranostic effect. The flexibility of GBNs cannot be limited to their biomedical applications and, these nanosystems emerge as a viable choice for an indirect effect on health by their future use as environmental cleaners. Indeed, GBNs can be used in bioremediation approaches alone or combined with other techniques such as phytoremediation. In summary, without ignoring the difficulties that GBNs still present before being deemed translatable to clinical and environmental applications, the purpose of this chapter is to provide an overview of the remarkable potential of GBNs on health by presenting examples of their versatility as nanotools for theranostics and bioremediation

Review Article Renal Biopsy: Use of Biomarkers as a Tool for the Diagnosis of Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a glomerulopathy associated with nephrotic syndrome and podocyte injury. FSGS occurs both in children and adults and it is considered the main idiopathic nephrotic syndrome nowadays. It is extremely difficult to establish a morphological diagnosis, since some biopsies lack a considerable quantifiable number of sclerotic glomeruli, given their focal aspect and the fact that FSGS occurs in less than half of the glomeruli. Therefore, many biological molecules have been evaluated as potential markers that would enhance the diagnosis of FSGS. Some of these molecules and receptors are associated with the pathogenesis of FSGS and have potential use in diagnosis

Stealth monoolein-based nanocarriers for delivery of siRNA to cancer cells

While the delivery of small interfering RNAs (siRNAs) is an attractive strategy to treat several clinical con- ditions, siRNA-nanocarriers stability after intravenous administration is still a major obstacle for the development of RNA-interference based therapies. But, although the need for stability is well recognized, the notion that strong stabilization can decrease nanocarriers efficiency is sometimes neglected. In this work we evaluated two stealth functionalization strategies to stabilize the previously validated dioctade- cyldimethylammonium bromide (DODAB):monoolein (MO) siRNA-lipoplexes. The nanocarriers were pre- and post-pegylated, forming vectors with different stabilities in biological fluids. The stealth nanocarriers behavior was tested under biological mimetic conditions, as the production of stable siRNA-lipoplexes is determinant to achieve efficient intravenous siRNA delivery to cancer cells. Upon incubation in human serum for 2 h, by fluorescence Single Particle Tracking microscopy, PEG-coated lipo- plexes were found to have better colloidal stability as they could maintain a relatively stable size. In addi- tion, using fluorescence fluctuation spectroscopy, post-pegylation also proved to avoid siRNA dissociation from the nanocarriers in human serum. Concomitantly it was found that PEG-coated lipoplexes improved cellular uptake and transfection efficiency in H1299 cells, and had the ability to silence BCR-ABL, affecting the survival of K562 cells. Based on an efficient cellular internalization, good silencing effect, good siRNA retention and good col- loidal stability in human serum, DODAB:MO (2:1) siRNA-lipoplexes coated with PEG-Cer are considered promising nanocarriers for further in vivo validation. Statement of Significance This work describes two stealth functionalization strategies for the stabilization of the previously validated dioctadecyldimethylammonium bromide (DODAB):monoolein (MO) siRNA-lipoplexes. These nanocarriers are capable of efficiently incorporating and delivering siRNA molecules to cells in order to silence genes whose expression is implicated in a pathological condition. The main objective was to functionalize these nanocarriers with a coating conferring protection to siRNA in blood without compromising its efficient delivery to cancer cells, validating the potential of DODAB:MO (2:1) siRNA-lipoplexes as therapeutic vec- tors. We show that the stealth strategy is determinant to achieve a stable and efficient nanocarrier, and that DODAB:MO mixtures have a very promising potential for systemic siRNA delivery to leukemic cells.FEDER through POFC-COMPETE and by national funds from FCT I.P. through the strategic funding UID/BIA/04050/2013 (CBMA) and PEst-C/FIS/UI0607/2013 (CFUM) and PTDC/QUI/69795/2006. We thank the support of the Frame Work Program 7 of the European Commission: BIOCAPS (316265, FP7/REGPOT) and Xunta de Galicia, Spain (Agrupamento INBIOMED, Grupo con potencial crecimiento) reference IF/00498/2012, scholarship SFRH/BD/68588/2010. NanoDelivery-I&D em Bionanotecnologia, Lda. for access to their equipment