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

Chitosan/carrageenan nanoparticles: effect of cross-linking with tripolyphosphate

Chitosan/carrageenan/tripolyphosphate nanoparticles were prepared by polyelectrolyte complexation/ionic gelation, the latter compound acting as cross-linker. The incorporation of the three components in the nanoparticle matrix was assessed by analytical techniques (FTIR, XPS and TOF-SIMS). Using chitosan/carrageenan nanoparticles as control, the effect of the cross-linker in the particles properties was studied. A decrease in size (from 450-500 nm to 150-300 nm) and in zeta potential (from +75 - +85 mV to +50 - +60 mV), and an increase in production yield (from 15-20% to 25-35%), and in stability (from one week to up to 9 months) were observed. Also, a correlation between positive to negative charge ratios in the formulations and the above characteristics was established. The small size and high positive surface charge make the developed chitosan/carrageenan/tripolyphosphate nanoparticles potential tools for an application in mucosal delivery of macromolecules

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

Anàlisi competencial de la unitat didàctica "Em sento bé?"

Es contrasta una Unitat Didàctica de Cicle Superior de Primària amb els criteris de riquesa competencial del CESIRE-CDEC

Oral magnesium supplementation improves endothelial function and attenuates subclinical atherosclerosis in thiazide-treated hypertensive women

Background: Epidemiological studies demonstrate an inverse association between serum magnesium and incidence of cardiovascular disease. Diuretics commonly cause hypomagneseamia. Method: We evaluated effects of magnesium supplementation on blood pressure (BP) and vascular function in thiazide-treated hypertensive women in a randomized, double-blind, clinical trial. Hypertensive women (40–65 years) on hydrochlorothiazide and mean 24-h BP at least 130/80 mmHg were divided into placebo and supplementation (magnesium chelate 600 mg/day) groups. Patients were evaluated for nutritional and biochemical parameters, office and ambulatory blood pressure monitoring, brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, assessment of carotid intima–media thickness, central hemodynamic parameters and pulse wave velocity at inclusion and after 6-month follow-up. Results: The magnesium group had a significant reduction in SBP (144 ± 17 vs. 134 ± 14 mmHg, P = 0.036) and DBP (88 ± 9 vs. 81 ± 8 mmHg, P = 0.005) at 6 months, without effect on plasma glucose, lipids, or arterial stiffness parameters. The placebo group showed a significant increase in carotid intima-media thickness (0.78 ± 0.13 vs. 0.89 ± 0.14 mm, P = 0.033) without change in the magnesium group (0.79 ± 0.16 vs. 0.79 ± 0.19 mm, P = 0.716) after 6 months. The magnesium group demonstrated a significant increase in variation of FMD vs. the placebo group (+3.7 ± 2.1 vs. 2.4 ± 1.2%, P = 0.015). There was a significant correlation between the intracellular magnesium variation and FMD (r = 0.44, P = 0.011). Conclusion: Magnesium supplementation was associated with better BP control, improved endothelial function and amelioration of subclinical atherosclerosis in these thiazide-treated hypertensive women

Envolvimento académico : confronto de expectativas e comportamentos em universitários do 1º ano

No presente trabalho analisam-se as expectativas dos estudantes acerca do seu envolvimento em diversas dimensões associadas à vida académica, assim como os comportamentos vivenciados uns meses após essa entrada tomando as mesmas dimensões. A amostra considerada é formada por 314 estudantes do 1º ano de três agrupamentos de cursos (Ciências e Engenharia; Ciências Económicas; e Ciências Sociais e Humanas) da Universidade do Minho. Estes alunos responderam, no início do ano e a meados do 2º semestre, ao Questionário de Envolvimento Académico (QEA; Soares & Almeida, 2001) nas suas versões de expectativas (Versão A) e comportamentos (Versão B). Os resultados sugerem níveis elevados de expectativas iniciais dos es- tudantes no momento da sua entrada na Universidade, registando-se uma diminuição significativa de tais índices no segundo momento da avaliação, em particular nas subescalas de envolvimento institucional e de envolvimento vocacional. Algumas oscilações nos resultados foram encontradas tomando os alunos de acordo com o agrupamento do curso frequentado, com o género, os níveis escolares dos pais ou o facto de frequentarem ou não um curso de 1º opção.This paper analyses students’ initial expectations concerning personal investment in different domains of academic life, as well as behaviours some months later in those same dimensions. The sample included 314 first year students of the University of Minho from three graduations areas: science and engineering, economic sciences, and social sciences and humanities. A questionnaire of academic involvement (QEA; Soares & Almeida, 2001) was applied to students at entrance (expectations version) and at middle of first semester (behaviours version). Results suggest higher levels of initial expectations at the entrance in the university, and a significant decrease of those levels some months later, namely in the institutional and vocational subscales. Some significant changes have been found considering the domain and option of graduation studies, gender and academic level of parents.Fundação Calouste Gulbenkian - Programa de Apoio a Projectos de Pesquisa no Domínio Educativo (2001/04) - projecto “Transição, adaptação e sucesso académico de jovens no Ensino Superior

Inhalable antitubercular therapy mediated by locust bean gum microparticles

Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 μm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy

Luteinizing hormone concentrations in healthy horses and horses with trigeminal-mediated headshaking over an 8-hour period.

BackgroundTrigeminal-mediated headshaking results from a low threshold for firing of the trigeminal nerve. A seasonal component has been implicated in onset of clinical signs, which occur during the spring and summer months. Geldings are overrepresented in the affected population and hormonal differences as compared to a healthy control population of geldings might contribute to headshaking.Objective/hypothesisTo assess concentrations of luteinizing hormone (LH) over an 8-hour period in gelded healthy controls and horses affected with headshaking. Our hypothesis was that geldings with seasonal headshaking would have higher concentrations of LH over an 8-hour period compared to control horses during the summer when affected horses manifested headshaking.AnimalsTwelve geldings (6 controls and 6 affected).MethodsProspective controlled trial. Blood samples were drawn every 15 minutes over an 8-hour time period during summer from all horses to measure circulating LH concentrations by using a radioimmunoassay for equine LH. All affected horses were actively affected by headshaking at the time of sample collection.ResultsNo statistically significant differences in LH concentrations were found throughout the study period in headshakers as compared to control horses. Time had no significant effect, but a slight decrease in LH concentrations was observed for all horses. The main limitation of the study was the low number of horses.Conclusions and clinical importanceHorses affected with headshaking did not have significant differences in circulating LH during the late summer as compared to control horses