Dendrimer Nanocarriers and their Aerosol Formulations for the Delivery of Therapeutics to and through the Lungs

In this presentation we discuss how the chemistry of dendrimer nanocarriers can be used to modulate their interaction with the pulmonary epithelium and how such knowledge can be used to develop efficient strategies for local or systemic delivery of drugs to and through the lungs. We also discuss particle engineering approaches that allow us to design portable oral inhalation formulations of the dendrimer nanocarriers with aerosols conducive to deep lung deposition. We employ a range of experimental and computational tools to probe the system at various size scales, from atomic to molecular to nano and micron, in order to design the nanocarriers and their formulations. We will discuss some of the potential applications of these carriers, including the formulation of biologics and small molecules, and targeting of intra-cellular organelles such as mitochondria, and demonstrate their applicability in treating an in vivo model of metastases to the lungs

Local Lung Targeting of Tumor Associated Macrophages Combined with Cytoreductive Therapy Decrease Tumor Burden in a Secondary Lung Cancer Model

Backgrounds. The efficacy of a locally administered small molecule colony stimulating factor 1 receptor inhibitor (CSF-1Ri), PLX3397, alone or in combination with cytoreductive therapy (paclitaxel) in reducing the tumor burden of an in vivo model of secondary lung cancer was investigated in this work. Local administration of immunotherapy to the lungs may enhance lung biodistribution of such therapies and reduce potential unwanted off-target toxicity. In addition, combination of such therapy with low dose standard of care chemotherapy may offer improved anti-tumor effects. Methods. Murine breast cancer cells (4T1, known to be highly metastasized to the lungs) were transduced to express the genes luciferase and tdTomato, and cells were injected to female Balb/c mice before being treated with PLX (intratracheally administered), paclitaxel (intravenously given), or the combination therapy. Both ex vivo bioluminescent imaging and lung weights were used to evaluate tumor burden. Western blot was performed using lung tumors to assess the effect of PLX3397 on its molecular target (phosphorylated CSF-1R). Immunofluorescence and Flowcytometry were utilized to examine the impact of treatment on tumorigenic tumor associated macrophages (M2 TAM). Results. Single-agent treatment partially decreased tumor burden, while combination therapy led to a significant reduction in tumor burden. PLX3397 significantly inhibited the expression of phosphorylated CSF-1R and reduced the number of M2 TAM without affecting the total macrophage population, thereby increasing the anti-tumorigenic (M1)/M2 ratio. Conclusion. Tumor burden reduction upon local administration of PLX3397 to the lungs correlates with the marked inhibition of the molecular target and the decrease in M2 TAM.https://scholarscompass.vcu.edu/gradposters/1065/thumbnail.jp

Extração de compostos volateis de carvões minerais utilizando-se fluidos supercriticos

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnologic

Avaliação do desempenho de ligações tubulares em estruturas de veículos pesados de passageiros por simulação numérica

Nesta Dissertação ir-se-á avaliar o desempenho de algumas ligações existentes nos veículos pesados de passageiros, através do Regulamento Eurocódigo 3. Nos últimos anos ocorreram diversos acidentes envolvendo este tipos de veículos, em que os mesmos causaram vítimas mortais e feridos graves. Serão testadas por simulação numérica algumas ligações pertencentes a elementos constituintes da superestrutura, em que esta é normalmente afectada com a ocorrência de acidentes. Assim sendo, o estudo de nós de ligação tem uma importância fulcral para que uma superestrutura suporte situações extremas e que resista a solicitações externas aplicadas. Iniciou-se esta Dissertação com o estudo da sinistralidade e de acidentes que envolvem veículos pesados de passageiros. No capítulo 2 abordou-se um programa que promove simulações numéricas de acidentes e estudo do comportamento dos passageiros em caso de acidente, sendo referido o Regulamento que homologa os veículos pesados de passageiros e os seus principais métodos. Abordaram-se os principais constituintes da estrutura de um veículo pesado de passageiros. No capítulo 3, é referido o Eurocódigo 3 em termos do estudo das ligações tubulares usadas neste tipo de veículos. No capítulo 4, fez-se o estudo e selecção de elementos a utilizar para a simulação numérica de casos preconizados pelo Eurocódigo 3 e estudaram-se três tipos de ligações que são usadas na construção da superestrutura deste tipo de veículos, tendo-se retirado conclusões deste estudo.In this thesis the performance of some existing joints used in the construction of passenger cars will be evaluated according to Regulation Eurocode 3. In past few years have occurred several accidents involving these types of vehicles, in which they have caused deaths and serious injuries. Some elements of the superstructure will tested by numerical simulation, which normally affected with the occurrence of accidents. Thus, the study of joints has a central importance for a superstructure. This thesis beginning with the study of accidents and accidents involving passenger cars. In chapter 2 it has a program that promotes numerical simulations of accidents and the study of the behaviour of occupants in case of accidents, being referred the Regulation that endorses the superstructure resistance in case of a rollover and its methods. It was studied the structural components of a superstructure. In chapter 3, it is referred the Eurocode 3 in terms of the study of tubular joints used in this type of vehicles. In chapter 4, it has been made the study and selection of finite elements to use in numerical simulation and studied three types of joints that are used in the superstructure of this types of vehicles

Violência doméstica contra mulheres negras na cidade do Rio de Janeiro

No contexto da violência doméstica, há variações notáveis de género, classe e cor. Como fenômeno de alta complexidade, faz-se necessária também a análise interseccional de como o género, a cor e os sistemas de classe interagem para auxiliar o combate à violência doméstica. O presente estudo opta por analisar a violência doméstica conjugal contra a mulher negra, na cidade do Rio de Janeiro. A presente pesquisa adotou como metodologia, o estudo quantitativo, documental e exploratório. Desse modo, o objetivo geral da pesquisa é caracterizar a vitimização por violência doméstica em mulheres negras. Para tal, a amostra utilizada refere-se a dados do Instituto de Segurança Público recolhidos no ano de 2018, 2019 e 2020 referentes à violência doméstica contra mulheres negras na cidade do Rio de Janeiro. Em relação a coleta de dados, foi construída uma grelha com as informações inerentes aos objetivos propostos nesta investigação e, a partir deste instrumento, o Instituto de Segurança Pública forneceu os dados referentes aos anos de 2018, 2019 e 2020. Por fim, a pesquisa concluiu que o contexto cultural e social do processo de violência doméstica conjugal contra a mulher negra configura especificidades próprias da vítima de violência doméstica que precisa ser tratada, estudada e combatida com uma atenção específica devido a alta incidência das mulheres negras como vítimas neste tipo de crime, razão pela qual esta deve ser também uma alerta aos órgãos de segurança pública responsáveis pelo combate ao crime de violência doméstica.In the context of domestic violence, there are notable variations of gender, class and colour. As a highly complex phenomenon, intersectional analysis of how gender, colour and class systems interact is also necessary to assist in combating domestic violence. The present study chooses to analyze marital domestic violence against black women in the city of Rio de Janeiro. The present research adopted as methodology, the quantitative, documental and exploratory study. Thus, the general objective of the research is to identify if black women in the city of Rio de Janeiro are in a situation of greater vulnerability with regard to marital domestic violence in relation to white women residing in the same city. To this end, the sample used refers to data from the Public Security Institute collected in the year 2018, 2019 and 2020 regarding domestic violence against black women in the city of Rio de Janeiro. Regarding data collection, a grid was built with the information inherent to the objectives proposed in this research and, from this instrument, the Public Security Institute provided the data referring to the years 2018, 2019 and 2020. Finally, the research concluded that the cultural and social context of the process of marital domestic violence against black women configures specificities specific to the victim of domestic violence that needs to be treated, studied and fought with specific attention due to the high incidence of black women as victims in this type of crime, which is why this should also be an alert to the public security agencies responsible for fighting the crime of domestic violence

Dendrimer Conjugation Enhances Tumor Penetration and Cell Kill of Doxorubicin in 3D Coculture Lung Cancer Models

Background: Doxorubicin (DOX) is a potent chemotherapeutic widely used for solid tumors (1). Despite high efficacy in 2D cell culture, DOX efficacy does not translate to in vivo lung cancer models (2). Major side effects such as cardiotoxicity may be alleviated with nano-based drug delivery systems (nanoDDS). However, tumor penetration of DOX and DOX-nanoDDS is largely unknown and is an additional barrier to effective clinical therapy (3). Here we describe a nanoDDS capable of enhancing the penetration of DOX. Methods: DOX was conjugated to generation 4 poly(amido-amine) dendrimers through (GFLG) tumor- liable bond. G4SA-GFLG-DOX was synthesized/characterized. spheroids were formed of (A549) lung adenocarcinoma cells and (3T3) fibroblasts. Spheroids were characterized for ECM components with immunohistochemistry. Confocal microscopy was used to evaluate the penetration, internalization, and colocalization of DOX and G4SA-GFLG-DOX. MTT assay and Caspase 3/7 to assess 2D and 3D cytotoxicity. Flow cytometry to determine cells uptake. Results: DOX conjugation to dendrimer resulted in G4SA-GFLG-DOX with ~5.5 DOX, 10±1 nm hydrodynamic diameter, and a -17±3 mV zeta-potential. Spheroids of (A549:3T3) were ECM- rich, developed ECM containing collagen-I, hyaluronan, laminin, and fibronectin. While DOX and G4SA-GFLG-DOX had similar toxicities in 2D model, G4SA-GFLG-DOX demonstrated a 3.1-fold greater penetration into spheroids compared to DOX and correlated to a greater efficacy as measured by caspase 3/7 activity. Also, flow cytometry showed higher uptake of G4SA- GFLG-DOX in cancer cells compared to fibroblasts. Conclusion: The work demonstrates enhanced penetration of DOX, via dendrimer conjugation, into an ECM- rich 3D lung cancer model. The enhanced penetration of G4SA-GFLG-DOX correlated with greater antitumor efficacy. Acknowledgements: We acknowledge partial financial support from the Center for Pharmaceutical Engineering and Sciences - School of Pharmacy at VCU. This study was supported by VCU Quest for Distinction and NSF (DRM #1508363). Microscopy was performed at the VCU Microscopy Facility, supported, in part, by funding from NIH-NCI Cancer Center Support Grant P30 CA016059. RA would like to acknowledge King Faisal University (KFU) and Saudi Arabian Cultural Mission (SACM) for a scholarship.https://scholarscompass.vcu.edu/gradposters/1091/thumbnail.jp

Integrality in a social protection network for adolescents: a reflection based on Giles Lipovetsky's thought

O propósito deste artigo é apresentar uma discussão sobre a integralidade como um paradigma, uma ideia-referência, do campo de conhecimento da Saúde Pública. Para isso apresentamos a exploração empírica dos elementos discursivos coletados numa rede de proteção social voltada ao adolescente dos quais deriva parte importante da prática de agentes de saúde. As experiências colhidas em campo a partir da ação dos articuladores da Política Municipal de Atenção à Criança e ao Adolescente, no Município de Suzano-SP, foram analisadas sob o ponto de vista de Gilles Lipovetsky. Essa análise situou a integralidade como ideia-referência proposta pelo campo de conhecimento da saúde pública, que questiona e provoca mudanças nas práticas médicas e de saúde inseridas na sociedade contemporânea, sobretudo no que se refere à atenção psicossocial.The purpose of this article is to present a discussion about integrality as a paradigm, an idea/reference in the field of knowledge of Public Health. For that we introduce the empiric exploration of discursive elements collected in a social protection network targeted at adolescents. These elements represent an important part of the health agents' practice. The experiences collected in the field from the actions of the articulators of the Municipal Policy of Child and Adolescent Care, in the city of Suzano, State of São Paulo, were analyzed from Giles Lipovetsky's point of view. This analysis situated integrality as an idea/reference proposed by the knowledge field of Public Health, which questions and provokes changes in the medical and health practices inserted in contemporary society - above all, in psychosocial assistance

Mapeamento de Nascentes e da Área de Preservação Permanente no Município de Céu Azul – PR

O uso exploratório do meio ambiente aliado à carência de um planejamento ambiental acarreta em diversas alterações do meio natural, diante disso, as técnicas de geoprocessamento vêm sendo utilizada como instrumento para o monitoramento e fiscalização de ambientes. Sendo assim, o presente estudo visou à elaboração do mapeamento de nascentes e da área de preservação permanente no município de Céu Azul, identificando os principais conflitos de uso e propondo medidas mitigatórias nas áreas que não apresentam o raio de preservação permanente de acordo com a legislação vigente. A identificação das nascentese de suas áreas de preservação, bem como a elaboração do mapa de uso e cobertura da terra foram desenvolvidos no software Google Earth Pro e confirmadas com visitas a campo. Com o mapeamento, verificou-se que das 71 nascentes presentes na área de estudo apenas 9 estão totalmente protegidas por vegetação, ou seja, 12,67% do total, o restante apresenta conflito de uso principalmente com a pastagem, contribuindo para o assoreamento e contaminação dos corpos d’água.