Carbon nanomaterials for the purification of antileukemic drugs

Getting older is the biggest risk factor for most fatal diseases, including cancer, heart disease and Alzheimer. To overcome such age-related society diseases, it is crucial to optimize the production and purification of biopharmaceuticals, such as nucleic acid-based products, antibodies and recombinant proteins and enzymes. Low cost production combined with high purity levels allow their routinely use by a widespread population. Continuous progresses have been made for the development of recombinant therapeutic enzymes. L-asparaginase (LA) is an antileukemic biopharmaceutical enzyme of current high-cost. LA is produced via fermentation and its purification usually comprises several steps that account up to 80% of its total production cost (1). This work aims to develop sustainable technologies to extract and purify LA. Reusable functionalized nanomaterials, namely carbon nanomaterials (CNTs), are used as cost-effective purification techniques for the target enzyme. Initially, the synthesis and modification of CNTs was performed. Different CNTs were obtained and used for the purification of LA. Commercial LA was used for the first purification tests, in order to understand the behaviour of the enzyme in contact with the nanomaterial. Experimental conditions, such as pH, and material/LA ratio, contact time were optimized. LA activity was quantified by Nessler reaction (2). The first results reveal a total adsorption of LA by the CNTs. Depending on the CNT functionalization/ treatment, different values of recovered activity of LA were obtained. The modified CNTs are shown to be very promising nanomaterials for the purification of LA. The LA was easily attached to CNTs by adsorption under mild conditions. CNTs supports can be a real alternative for a single step immobilization/purification of LA.publishe

O Parque Natural Hidrogeológico de Moura : contributos para a sua definição

O aquífero carbonatado cársico de Moura-Ficalho é uma das mais importantes reservas de água na região do Alentejo. A área caracteriza-se por condições climatéricas, geográficas, geológicas, e um potencial hídrico que a tornam ideal para o estudo de metodologias aplicadas à gestão de sistemas cársicos em regiões secas, mas com importante procura de água. Por sua vez os aquíferos cársicos são sistemas complexos e extremamente vulneráveis à contaminação e a alterações originadas pelas acções do homem nos ecossistemas locais, sendo por este motivo crucial a análise entre outros das fontes de contaminação, das áreas preferenciais de recarga e das direcções locais e regionais de fluxo. Estas razões justificaram a criação da figura de Parque Natural Hidrogeológico, o qual à semelhança de outros parques para outros recursos naturais, permitirá a protecção de um recurso natural sensível. Nesse contexto reveste-se de grande importância o estudo dos fenómenos e a evolução natural, sem restrições à priori quanto ao uso do solo. Tudo se passa como se o Parque Natural Hidrogeológico funcionasse como um Laboratório natural, à escala real, onde as interacções entre as componentes do ciclo hidrológico, as actividades humanas e os ecossistemas são estudados como um todo. Esta abordagem requer a análise do ciclo hidrológico em corte vertical entre a baixa atmosfera e a base dos aquíferos. É portanto uma abordagem mais rica que as abordagens clássicas nas quais o ciclo hidrológico é interrompido no topo dos aquíferos. De forma a preservar a perspectiva global do ciclo é necessário conhecer os fenómenos nas zonas de transição: atmosfera - água (fundamentalmente entre a zona vadosa e a zona saturada); água superficial - água subterrânea. Nestas zonas de transição as alterações das condições físicoquímicas são acompanhadas por alterações bióticas importantes. Dadas as relações entre a componente biótica e abiótica, uma não deve ser estudada sem o conhecimento da outra. Os ecossistemas nas zonas de transição são designados de ecotopos. Uma vez que os ecotopos são ecossistemas contínuos, isto é, não há variações abruptas no número e diversidade de indivíduos, então também as variações físico-químicas devem ser contínuas. O estudo dos ecotopos ajuda a perceber as transições contínuas nas zonas de interface, sem que haja a necessidade de impor fronteiras discretas - é portanto uma abordagem mais perfeita para o carácter contínuo dos processos naturais. As metodologias usadas para o estudo do Parque permitirão desenvolver ferramentas integradas de gestão, tecnicamente mais evoluídas uma vez que consideram o ciclo hidrológico como contínuo. Estas ferramentas poderão então ser utilizadas como auxiliares de decisão. O cruzamento de informação entre os regimes de protecção especial já implementados ou a implementar e as novas áreas de protecção dos recursos hídricos será facilitada pela presença de variáveis repetidas em ambos. Deve referir-se que a metodologia proposta utiliza a caracterização dos ecossistemas como um meio e não como um fim. A caracterização hidrológica do sistema terá um carácter multidisciplinar pelo uso integrado de diversas técnicas e métodos: geofísica, detecção remota, análise de imagem, geoestatística, morfologia matemática, análise multivariada de dados, modelação matemática

New WC-Cu composites for the divertor in fusion reactors

ABSTRACT: The requirements for the divertor components of future fusion reactors are challenging and therefore a stimulus for the development of new materials. In this paper, WC-Cu composites are studied for use as thermal barrier between the plasma facing tungsten tiles and the copper-based heat sink of the divertor. Composite materials with 50% vol. WC were prepared by hot pressing and characterized in terms of microstructure, density, expansion coefficient, elastic modulus, Young's modulus and thermal diffusivity. The produced materials consisted of WC particles homogeneously dispersed in a Cu matrix with densifications between 88% and 98%. The sample with WC particles coated with Cu evidenced the highest densification. The thermal diffusivity was significantly lower than that of pure copper or tungsten. The sample with higher densification exhibits a low value of Young's modulus (however, it is higher compared to pure copper), and an average linear thermal expansion coefficient of 13.6 x 10(-6) degrees C-1 in a temperature range between 100 degrees C and 550 degrees C. To estimate the behaviour of this composite in actual conditions, a monoblock of the divertor in extreme conditions was modelled. The results predict that while the use of WC-Cu interlayer leads to an increase of 190 degrees C on the temperature of the upper part of the monoblock when compared to a pure Cu interlayer, the composite will improve and reduce significantly the cold-state stress between this interlayer and the tungsten.info:eu-repo/semantics/publishedVersio

99mTc-MAA for Lung Perfusion Scintigraphy: Impact of Counting Method on the Effective Number of Particles Administered and Particle Aggregation Over Time

Introduction: 99mTc-MAA (macroaggregates of albumin) is the selected radiopharmaceutical for the Lung Perfusion Scintigraphy. It is retained in lung capillaries by mechanical blockage resulting in local microembolization. Care should be taken concerning not only particle size butalso the number of particles administered to patients, particularly those who present with special conditions (pulmonary hypertension, shunt or lung transplant). European Pharmacopoeia only requires the assessment of particle size. This work aims to characterize particle size and particle aggregation of two commercial brands of MAA kits and to compare particle counting methods

Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/Anthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain a challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthracis and Bacillus cereus as potent and selective bactericides. Biological studies of the synthesized compound series differing in the anomeric atom, glycone configuration and deoxygenation pattern show that the latter is indeed a key modulator of efficacy and selectivity. Biomolecular simulations show no tendency to pore formation, whereas differential metabolomics and genomics rule out proteins as targets. Complete bacteria cell death in 10 min and cellular envelope disruption corroborate an effect over lipid polymorphism. Biophysical approaches show monolayer and bilayer reorganization with fast and high permeabilizing activity toward phosphatidylethanolamine membranes. Absence of bacterial resistance further supports this mechanism, triggering innovation on membrane-targeting antimicrobials.The European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. We thank the Management Authorities of the European Regional Development Fund and the National Strategic Reference Framework for the support of the Incentive System - Research and Technological Development Co-Promotion FACIB Project number 21457. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of projects UID/Multi/00612/2013, FCT/UID/ Multi/04046/2013, IF/00808/2013/CP1159/CT0003, PTDC/BBBBQB/6071/2014, as well as for the post-doc grant SFRH/BPD/42567/2007 (A.M.), the Ph.D. grants SFRH/BDE/51998/2012 (C.D.), and SFRH/BDE/51957/2012 (J.P.P.), both co-sponsored by CIPAN, and also for the Ph.D. grant SFRH/BD/116614/2016 (R.N.).info:eu-repo/semantics/publishedVersio

Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood

Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4+ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009), which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8+ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4+ and CD8+ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaCentro Assistencial Cruz de MaltaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUNIFESP, Depto. de MedicinaUNIFESP, Depto. de PediatriaSciEL