In Vitro Evaluation of Curcumin- and Quercetin-Loaded Nanoemulsions for Intranasal Administration: Effect of Surface Charge and Viscosity

The nose-to-brain delivery of neuroprotective natural compounds is an appealing approach for the treatment of neurodegenerative diseases. Nanoemulsions containing curcumin (CUR) and quercetin (QU) were prepared by high-pressure homogenization and characterized physicochemically and structurally. A negative (CQ_NE—), a positive (CQ_NE+), and a gel (CQ_NEgel) formulation were developed. The mean particle size of the CQ_NE— and CQ_NE+ was below 120 nm, while this increased to 240 nm for the CQ_NEgel. The formulations showed high encapsulation efficiency and protected the CUR/QU from biological/chemical degradation. Electron paramagnetic resonance spectroscopy showed that the CUR/QU were located at the interface of the oil phase in the proximity of the surfactant layer. The cytotoxicity studies showed that the formulations containing CUR/QU protected human nasal cells from the toxicity evidenced for blank NEs. No permeation across an in vitro model nasal epithelium was evidenced for CUR/QU, probably due to their poor water-solubility and instability in physiological buffers. However, the nasal cells' drug uptake showed that the total amount of CUR/QU in the cells was related to the NE characteristics (CQ NE— > CQ NE+ > CQ_NEgel). The method used allowed the obtainment of nanocarriers of an appropriate size for nasal administration. The treatment of the cells showed the protection of cellular viability, holding promise as an anti-inflammatory treatment able to prevent neurodegenerative diseases

Experiências leitoras na formação inicial de professores: reflexões sobre o PIBID

O estudo aborda reflexivamente as implicações de experiências leitoras na formação inicial de professores, considerando as práticas de aprendizagem da profissão docente desenvolvidas em um subprojeto do Programa Institucional de Bolsa de Iniciação à Docência (PIBID), implementado na capital baiana, em uma Licenciatura em Pedagogia.  Relaciona as contribuições dos aportes teóricos-metodológicos contemporâneos do campo das pesquisas (Auto)biográficas em educação, formação docente e leitura, tendo em vista tratar, de forma analítica, sobre as relações entre experiências leitoras vivenciadas por licenciandos, bolsistas de Iniciação à Docência (ID) e seus percursos de  formação  na construção  de novos modos de atuação didática no contexto da Escola Básica. O acompanhamento dos processos formativos realizados pela presente pesquisa permite destacar os seguintes aspectos como resultados da inserção regular e sistemática dos bolsistas de ID em sucessivas agendas e práticas de leitura, a saber: a potência das práticas leitoras para a construção de sentidos; contribuição para o desenvolvimento da autonomia do professor em iniciação profissional; a repercussão das experiências de formação no PIBID para a criação de uma cultura leitora em licenciandos de Pedagogia, com reverberação na criação de estratégias favoráveis às novas gerações de leitores na Escola Básica; a experimentação didática como derivada da ampliação de repertórios de leitura pelos bolsistas de ID; a virtuosidade dos rituais de leitura em percursos formativos de professores; o reconhecimento da dimensão emancipatória do ‘ato de ler’, especialmente na Escola Pública; a percepção das práticas leitoras como elo que aproxima as realidades, tensões e sujeitos na relação Escola e Universidade

The nasal delivery of nanoencapsulated statins – An approach for brain delivery

© 2016 Clementino et al. Purpose: Along with their cholesterol-lowering effect, statins have shown a wide range of pleiotropic effects potentially beneficial to neurodegenerative diseases. However, such effects are extremely elusive via the conventional oral administration. The purpose of the present study was to prepare and characterize the physicochemical properties and the in vivo biodistribution of simvastatin-loaded lecithin/chitosan nanoparticles (SVT-LCNs) suitable for nasal administration in view of an improved delivery of the statins to the brain. Materials and methods: Chitosan, lecithin, and different oil excipients were used to prepare nanocapsules loaded with simvastatin. Particle size distribution, surface charge, structure, simvastatin loading and release, and interaction with mucus of nanoparticles were determined. The nanoparticle nasal toxicity was evaluated in vitro using RPMI 2651 nasal cell lines. Finally, in vivo biodistribution was assessed by gamma scintigraphy via Tc99m labeling of the particles. Results: Among the different types of nanoparticles produced, the SVT-LCN_MaiLab showed the most ideal physicochemical characteristics, with small diameter (200 nm), positive surface charge (+48 mV) and high encapsulation efficiency (EE; 98%). Size distribution was further confirmed by nanoparticle tracking analysis and electron microscopy. The particles showed a relatively fast release of simvastatin in vitro (35.6%±4.2% in 6 hours) in simulated nasal fluid. Blank nanoparticles did not show cytotoxicity, evidencing that the formulation is safe for nasal administration, while cytotoxicity of simvastatin-loaded nanoparticles (IC50) was found to be three times lower than the drug solution (9.92 vs 3.50 μM). In rats, a significantly higher radioactivity was evidenced in the brain after nasal delivery of simvastatin-loaded nanoparticles in comparison to the administration of a similar dose of simvastatin suspension. Conclusion: The SVT-LCNs developed presented some of the most desirable characteristics for mucosal delivery, that is, small particle size, positive surface charge, long-term stability, high EE, and mucoadhesion. In addition, they displayed two exciting features: First was their biodegradability by enzymes present in the mucus layer, such as lysozyme. This indicates a new Trojan-horse strategy which may enhance drug release in the proximity of the nasal mucosa. Second was their ability to enhance the nose-to-brain transport as evidenced by preliminary gamma scintigraphy studies

EVOLUÇÃO DA INFRAESTRUTURA GRAVIMÉTRICA NO BRASIL

Com o avanço das técnicas de medição da aceleração de gravidade, houve considerável aumento das aplicações gravimétricas em diversos segmentos de atividades mundo afora. Por conseguinte, uma profusão de dados gravimétricos espaciais, aéreos, marinhos e terrestres tem sido adquirida, sobretudo desde meados do século passado. Ao desafio de aprimorar as aplicações, soma-se o interesse da comunidade científica em estabelecer padrões acerca da aquisição e manutenção do acervo auferido, visando dar maior homogeneidade às informações obtidas e disponibilizadas ao usuário. No quadro brasileiro, a falta de uma política gravimétrica nacional tem acarretado iniciativas difusas, fazendo com que cada instituição preencha suas necessidades de forma independente e sem a devida padronização. O presente artigo visa a trazer à tona informações que possibilitem um melhor conhecimento das atividades gravimétricas até então empreendidas em território brasileiro, retratando as principais técnicas e instrumentos utilizados. Adicionalmente, retrata-se brevemente a trajetória das principais instituições que atuam no campo da gravimetria, no intuito de conhecer o passado, compreender o presente e antever futuras ações devidamente concatenadas

Evaluation the best condition of Fibrinolytic protease production using factorial design by Streptomyces sp DPUA 1573

XI Reunião Regional Nordeste da SBBq | 4th International Symposium in Biochemistry of Macromolecules and BiotechnologyFibrinolytic enzymes have the ability to degrade fibrin clots formed for avoiding intravascular thrombosis. In the pharmaceutical industry there is a search for new fibrinolytic agent that reduces the production cost and increasing productivity. The use of microorganism for enzyme production, such as the genus Streptomyces has been reported. Streptomyces is a Gram-positive bacteria, responsible for producing many bioactive compounds and extracellular enzymes of pharmaceutical interest. This study aimed to evaluated the production of fibrinolytic protease by Streptomyces sp DPUA 1573. Microbial cells were cultivated in the ISP2 for 48 hours, after this period the strains were inoculated in MS2 (soybean medium) that according with factorial design 24 (concentrations of soybean 0.5; 1.0 and 1.5%, glucose 0; 0.5 and 1.0% and different speeds 150 rpm; 200 rpm and 250 rpm and temperature 28C; 30C and 32C). The factorial design was analyzed by variance analysis (anova) and the glucose concentration showed a positive and significative effect. The results showed that the variable interaction had significant effect. that the best condition was composed 1.5% soybean, 1% glucose, 28 ºC and 150 speed in 48 hours, with production fibrinolytic 1391.66 U/mL. These values were higher than those reported in the literature. However these results show the biggest potencial in production fibrinolytic enzyme by Streptomyces.info:eu-repo/semantics/publishedVersio

A MULTICENTER, OBSERVATIONAL, AMBISPECTIVE STUDY EVALUATING EFFICACY AND SAFETY OF GENERIC IMATINIB COMPARED TO GLEEVEC IN CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE-3 MONTHS RESPONSE ANALYSIS

Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP, BrazilUniv Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, BrazilInst Nacl Cancer, Rio De Janeiro, BrazilFac Med, Sao Paulo, BrazilUniv Sao Paulo, Sao Paulo, BrazilHemorio, Rio De Janeiro, BrazilHosp Clin Porto Alegre, Porto Alegre, RS, BrazilCtr Pesquisa Oncol Santa Catarina, Florianopolis, SC, BrazilUniv Fed Bahia, Salvador, BA, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilInst Estudos & Pesquisas Sao Lucas, Sao Paulo, BrazilUniv Estadual Campinas, Campinas, SP, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc

Evidence of Aquaporin 4 Regulation by Thyroid Hormone During Mouse Brain Development and in Cultured Human Glioblastoma Multiforme Cells

Accumulating evidence indicates that thyroid function and the thyroid hormones L-thyroxine (T4) and L-triiodothyronine (T3) are important factors contributing to the improvement of various pathologies of the central nervous system, including stroke, and various types of cancer, including glioblastoma multiforme (GBM). Low levels of T3 are correlated with the poorest outcome of post-stroke brain function, as well as an increased migration and proliferation of GBM tumor cells. Thyroid hormones are known to stimulate maturation and brain development. Aquaporin 4 (AQP4) is a key factor mediating the cell swelling and edema that occurs during ischemic stroke, and plays a potential role in the migration and proliferation of GBM tumor cells. In this study, as a possible therapeutic target for GBM, we investigated the potential role of T3 in the expression of AQP4 during different stages of mouse brain development. Pregnant mice at gestational day 18, or young animals at postnatal days 27 and 57, received injection of T3 (1 μg/g) or NaOH (0.02 N vehicle). The brains of mice sacrificed on postnatal days 0, 30, and 60 were perfused with 4% paraformaldehyde and sections were prepared for immunohistochemistry of AQP4. AQP4 immunofluorescence was measured in the mouse brains and human GBM cell lines. We found that distribution of AQP4 was localized in astrocytes of the periventricular, subpial, and cerebral parenchyma. Newborn mice treated with T3 showed a significant decrease in AQP4 immunoreactivity followed by an increased expression at P30 and a subsequent stabilization of aquaporin levels in adulthood. All GBM cell lines examined exhibited significantly lower AQP4 expression than cultured astrocytes. T3 treatment significantly downregulated AQP4 in GBM-95 cells but did not influence the rate of GBM cell migration measured 24 h after treatment initiation. Collectively, our results showed that AQP4 expression is developmentally regulated by T3 in astrocytes of the cerebral cortex of newborn and young mice, and is discretely downregulated in GBM cells. These findings indicate that higher concentrations of T3 thyroid hormone would be more suitable for reducing AQP4 in GBM tumorigenic cells, thereby resulting in better outcomes regarding the reduction of brain tumor cell migration and proliferation