Hybrid Nanoparticles as a Novel Tool for Regulating Psychosine-Induced Neuroinflammation and Demyelination In Vitro and Ex vivo

Polymeric nanoparticles are being extensively investigated as an approach for brain delivery of drugs, especially for their controlled release and targeting capacity. Nose-to-brain administration of nanoparticles, bypassing the blood brain barrier, offers a promising strategy to deliver drugs to the central nervous system. Here, we investigated the potential of hybrid nanoparticles as a therapeutic approach for demyelinating diseases, more specifically for Krabbe’s disease. This rare leukodystrophy is characterized by the lack of enzyme galactosylceramidase, leading to the accumulation of toxic psychosine in glial cells causing neuroinflammation, extensive demyelination and death. We present evidence that lecithin/chitosan nanoparticles prevent damage associated with psychosine by sequestering the neurotoxic sphingolipid via physicochemical hydrophobic interactions. We showed how nanoparticles prevented the cytotoxicity caused by psychosine in cultured human astrocytes in vitro, and how the nanoparticle size and PDI augmented while the electrostatic charges of the surface decreased, suggesting a direct interaction between psychosine and the nanoparticles. Moreover, we studied the effects of nanoparticles ex vivo using mouse cerebellar organotypic cultures, observing that nanoparticles prevented the demyelination and axonal damage caused by psychosine, as well as a moderate prevention of the astrocytic death. Taken together, these results suggest that lecithin-chitosan nanoparticles are a potential novel delivery system for drugs for certain demyelinating conditions such as Krabbe’s disease, due to their dual effect: not only are they an efficient platform for drug delivery, but they exert a protective effect themselves in tampering the levels of psychosine accumulation

Legislação de acesso a recursos genéticos e conhecimentos tradicionais associados e repartição de benefícios.

Sistema internacional de acesso e repartição de benefícios; Sistema brasileiro de acesso e repartição de benefícios; Exigências administrativas; Processo administrativo; Termos de transferência de material; Relatórios; Legislaçãp

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

MANF Is Neuroprotective against Ethanol-Induced Neurodegeneration through Ameliorating ER Stress

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in ethanol-induced neurodegeneration and its association with ER stress regulation, we established a CNS-specific Manf knockout mouse model and examined the effects of MANF deficiency on ethanol-induced neuronal apoptosis and ER stress using a third-trimester equivalent mouse model. We found MANF deficiency exacerbated ethanol-induced neuronal apoptosis and ER stress and that blocking ER stress abrogated the harmful effects of MANF deficiency on ethanol-induced neuronal apoptosis. Moreover, using an animal model of ER-stress-induced neurodegeneration, we demonstrated that MANF deficiency potentiated tunicamycin (TM)-induced ER stress and neurodegeneration. A whole transcriptome RNA sequencing also supported the functionality of MANF in ER stress modulation and revealed targets that may mediate the ER stress-buffering capacity of MANF. Collectively, these results suggest that MANF is a neurotrophic factor that can protect neurons against ethanol-induced neurodegeneration by ameliorating ER stress

Desenvolvimento inicial de mudas de ipê-verde em solo do Cerrado.

bitstream/item/68997/1/044-lima-desenvolvimento.pdfPublicado também no Cadernos de Agroecologia, v. 7, n.2, 2012

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

Sustainability in the business context: Contributions of product design.

O trabalho objetivou desenvolver um artefato eco eficiente para um negócio sustentável, para isto, foi necessário realizar um estudo sobre aspectos da sustentabilidade, interligando estes a movimentos da cultura DIY e minimalista. Esses estudos culturais relacionados ao tema, mostraram-se de suma importância para a realização do artefato final, que traz como principais características elementos da estética sustentável e referências destas culturas. Dentro do universo e premissas sustentáveis, a escolha foi desenvolver um artefato para foodbike, direcionada ao público ambulante, sendo uma alternativa econômica aos microempreendedores. A matéria prima escolhida – palete – teve uma relevância importante para economia local, uma vez que se trata de um material de reutilização, com ótimas qualidades mecânicas, aspecto primordial para confecção do artefato final. Ao trabalhar materiais com grande potêncial para ressignificação, foi necessário perceber que a cada passagem uma nova estética surge aos olhos dos consumidores.The objective of the work was to develop an eco-efficient artefact for a sustainable business, for this, it was necessary to carry out a study on aspects of sustainability, interconnecting these to movements of the DIY and minimalist culture. These cultural studies related to the theme have proved to be of utmost importance for the final artifact, which brings as main characteristics elements of sustainable aesthetics and references of these cultures. Within the universe and sustainable premises, the choice was to develop an artifact for foodbike, aimed at the traveling public, being an economic alternative to microentrepreneurs. The chosen raw material - pallet - had an important relevance for local economy, since it is a material of reutilization, with excellent mechanical qualities, primordial aspect for confection of the final artifact. When working materials with great potential for re-signification, it was necessary to realize that at each passage a new aesthetic appears in the eyes of the consumers

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

Farming system for irrigated crops in the submédio São Francisco region. I. Industrial tomato

Em trabalho realizado no Centro de Pesquisa Agropecuária do Trópico Semi-Árido, com a finalidade de formular sistemas de produção mais rentáveis para a cultura do tomate (Lycopersicon esculentum Mill.) industrial, constatou-se que, para os dois sistemas de cultivo confrontados (sistema tradicional e sistema modificado), o custo total de produção foi menor no sistema modificado, tendo ocorrido aumento da produtividade e da receita líquida. O emprego da tecnologia gerada pela pesquisa ocasionou uma redução dos custos da ordem de 40%, variando de Cr $126.563,00/ha no sistema tradicional, para Cr$ 75.262,00/ha no sistema modificado. Com a elevação da produtividade e a redução dos custos, a receita líquida variou de Cr $182.462,59/ha, no sistema tradicional, para Cr$ 393.751,41/ha no modificado. Com isto, a razão benefício/custo, que foi de Cr $1,44 no sistema tradicional, elevou-se para Cr$ 5,23 no sistema modificado.With the objective of defining more lucrative farming systems for the industrial tomato (Lycopersicon esculentum Mill.) crop, the Centro de Pesquisa Agropecuária do Trópico Semi-Árido, in the State of Pernambuco, Brazil, has carried out a study comparing two cropping systems: tradicional, which is the farmers technology; and improved, which is the research technology. The total cost was found to be lower in the improved system with an increase in the productivity and net income. The use of the research technology gave a rectuction of 40% in the total cost, varying from Cr $126.563,00/ha in the traditional system to Cr$ 75.262,00 in the improved system, With the increase in the productivity and the cost reduction, the net income varied from Cr$182.462,59/ha in the traditional system to Cr$ 393.751,41/ha in the improved system. Thus, the benefit/cost ratio was Cr $1,44 in the traditional system and Cr$ 5,23 in the improved system

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