Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy

The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.Portuguese Foundation for Science and Technology [PTDC/DTP-FTO/0094/2012, UID/Multi/04326/2013, UID/BIM/04773/2013]; CAPES-Brazil [BEX 1168/13-4

Tra norma e uso: la dislocazione a sinistra nelle grammatiche di italiano per apprendenti stranieri

In this paper, I will observe how 34 recent Italian grammars for foreigners describe and illustrate the left-dislocation. Three different types of grammars sharing similar attitudes towards the construction have been found: (1) shy grammars, in which the left-dislocation is sometimes briefly described from a formal point of view, but very often found in the sentences given as examples of Italian language when describing other linguistic phenomena; (2) oblivious grammars, in which the left-dislocation is neither described nor included in the sentences given as examples of Italian language; (3) aware grammars, in which the left-dislocation is described in detail from both a formal and functional point of view and where a more or less rich presence of the construction is found in the exemplifications. A deeper analysis will highlight other features each type of grammar shares, such as the educational/professional background of the authors and the intended audience of the grammar being students of Italian as a second language or as a foreign language. These features are factors that play a role in the treatment received by the left-dislocation

La actuación del síndico en los procesos concursales

Fil: Buttini, Laura del Carmen. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Cevantes, Mario Alberto. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas

Inhalable spray-dried chondroitin sulphate microparticles: effect of different solvents on particle properties and drug activity

Spray-drying stands as one of the most used techniques to produce inhalable microparticles, but several parameters from both the process and the used materials affect the properties of the resulting microparticles. In this work, we describe the production of drug-loaded chondroitin sulphate microparticles by spray-drying, testing the effect of using different solvents during the process. Full characterisation of the polymer and of the aerodynamic properties of the obtained microparticles are provided envisaging an application in inhalable tuberculosis therapy. The spray-dried microparticles successfully associated two first-line antitubercular drugs (isoniazid and rifabutin) with satisfactory production yield (up to 85%) and drug association efficiency (60%-95%). Ethanol and HCl were tested as co-solvents to aid the solubilisation of rifabutin and microparticles produced with the former generally revealed the best features, presenting a better ability to sustainably release rifabutin. Moreover, these presented aerodynamic properties compatible with deep lung deposition, with an aerodynamic diameter around 4 μm and fine particle fraction of approximately 44%. Finally, it was further demonstrated that the antitubercular activity of the drugs remained unchanged after encapsulation independently of the used solvent.UID/Multi/04326/2019; SFRH/BD/52426/2013; ED481B 2018/071info:eu-repo/semantics/publishedVersio

Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles

Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors. (C) 2017 Elsevier B.V. All rights reserved.National Portuguese funding through FCT - Fundacao para a Ciencia e a Tecnologia [PTDC/DTP-FTO/0094/2012, UID/BIM/04773/2013, UID/Multi/04326/2013, UID/QUI/00100/2013, PEst-OE/QUI/UI4023/2011

Influência da posição do tronco nas características do carvão de Eucalyptus benthamii.

bitstream/item/92723/1/CT-Edson.pd

Районирование нефтегазоносности пласта ю15 нюрольской мегавпадины (на основе результатов палеотемпературного моделирования)

Ранее было выполнено палеотемпературное моделирование, картирование по геотемпературному критерию палеоочагов генерации тогурских нефтей в пределах Нюрольской мегавпадины. В настоящей работе рассчитано распределение относительной плотности ресурсов первично-аккумулированных тогурских нефтей с учетом толщин пласта Ю15, выполнено районирование резервуара для постановки поисковых работ

Spatial and temporal expression profiling of cell-wall invertase genes during early development in hybrid poplar

Cell-wall invertase genes are spatially and temporally regulated in several plant species, including Daucus carota L., Lycopersicon esculentum L. and Solanum tuberosum L. However, few studies of cell-wall invertase genes of trees have been conducted, despite the importance of trees as a source of lignocellulosic biopolymers.We identified three putative cell-wall invertase genes in hybrid poplar (Populus alba L. × grandidentata Michx.) that showed higher homology to each other than to cell-wall invertases of other dicotyledonous species, with two of the genes (Pa×gINV2 and Pa×gINV3) appearing as a genomic tandem repeat. These genes are more similar to each other than to tandemly repeated cell-wall invertases of other plants, perhaps indicating parallel evolution of a duplication event with cell-wall invertases in dicotyledons. Spatial and temporal expression analyses throughout a complete annual cycle indicated that Pa×gINV1 and Pa×gINV2 are highly regulated in vegetative tissues during three distinct growth phases: early growth, dormancy and post-dormancy. Expression of the third gene (Pa×gINV3) appears to be tightly regulated and may represent a floral-specific cell-wall invertase. Of the two genes expressed in vegetative tissues, Pa×gINV1 appears to be exclusively involved in processes related to dormancy, whereas Pa×gINV2 appears to encode an enzyme involved in phloem unloading and in providing actively growing tissues, such as developing xylem, with the energy and carbon skeletons necessary for respiration and cell wall biosynthesis