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

An Online Learning Method for Microgrid Energy Management Control*

We propose a novel Model Predictive Control (MPC) scheme based on online-learning (OL) for microgrid energy management, where the control optimisation is embedded as the last layer of the neural network. The proposed MPC scheme deals with uncertainty on the load and renewable generation power profiles and on electricity prices, by employing the predictions provided by an online trained neural network in the optimisation problem. In order to adapt to possible changes in the environment, the neural network is online trained based on continuously received data. The network hyperparameters are selected by performing a hyperparameter optimisation before the deployment of the controller, using a pretraining dataset. We show the effectiveness of the proposed method for microgrid energy management through extensive experiments on real microgrid datasets. Moreover, we show that the proposed algorithm has good transfer learning (TL) capabilities among different microgrids

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

Association of bovine papillomavirus type 2 (BPV-2) and urinary bladder tumours in cattle from the Azores archipelago

Copyright (c) 2010 Elsevier Ltd. All rights reserved.Urinary bladder tumours in cattle are caused by chronic ingestion of bracken fern and BPV-1/2 infection. The objective of the present study was to assess if BPV-2 was present in urinary bladder lesions from cattle with chronic enzootic haematuria (CEH) from the Azores archipelago (Portugal), in order to gain further information regarding the epidemiologic distribution of this virus. Samples were analysed using PCR specific primers for BPV-2 DNA and an immunohistochemistry for BPV E5 oncoprotein detection. We found a 28% incidence rate of BPV-2 DNA in different types of tumours and cystitis cases (13 out of 46 samples). Tested positive samples for PCR were also positive for the viral E5 oncoprotein; protein immunolabeling was mainly detected within the cytoplasm of urothelial cells, displaying a juxtanuclear distribution. This is the first report of BPV-2 detection in urinary bladder tumours associated with CEH in cattle from the Azores archipelago.Direcção Regional da Ciência e Tecnologia, Governo dos Açores, Portugal; Università degli Studi di Napoli Federico-II (Italia); CIRN (Centro de Investigação em Recursos Naturais, Universidade dos Açores) (Portugal)

The Role of Mesenteric Adipose Tissue in Crohn’s Disease

Inflammatory bowel disease (IBD) has become an increasingly frequent chronic health problem in the last few decades, particularly in developing countries. In young adults, one of the most common forms of IBD is Crohn’s disease (CD). CD is a multifactorial genetic disease characterized by a transmural granulomatous inflammation that especially affects the terminal ileum and the colon. As it involves defective inflammatory pathways, the immune adaptive complex, and environmental factors, this disease has periods of remission and recurrence followed by diarrhea, abdominal pain, and malnutrition, which often lead to lumen bowel stenosis associated to multiple fistulas. In addition, the growth of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Evidence linking the development of mesenteric and intestinal alterations in CD is increasing. The aim of this chapter is to address adipose tissue in general, the morphological and functional differences between its compartments, the main characteristics of MAT in CD, and its possible role in the etiopathology of this immune-mediated disease

Using different levels of information in planning green infrastructure in Luanda, Angola

UIDB/04647/2020 UIDP/04647/2020Integrating natural processes to build areas through the creation of green infrastructure (GI) in Africa with its rapid urbanisation is a challenge because of the information base. The aim of this paper is planning a GI linking biophysical, social, and legal contents in a specific Africa country with an approach that combines different scales and different levels of data and information. The paper proposes a framework beginning at the macro scale to integrate and operationalise the definition of GI in an African context, namely for the Luanda metropolitan area. The approach to nature and ecological structure (GI) has four phases: analysis, integration, diagnosis and proposal. All steps are developed in a GIS environment and consider variations in the biophysical, social, cultural, and legal dimensions. The research discusses the problems in collecting existing information and leads with missing data within the context of urbanisation growth and climate change adaptation. The proposed green infrastructure includes protected areas (existing and proposed), natural values, risk areas, rivers, and agricultural areas, to increase resilience and flexibility in an adaptation context. The results allow to include in the GI the mangrove areas, native flora, vegetated slopes, and riverbanks, providing a buffering function for natural hazards, crucial for these regions, with the aim to achieve the needs of creating a strategic GI to be implemented into the Luanda General Master Plan.publishersversionpublishe

Inhalable chitosan microparticles for simultaneous delivery of isoniazid and rifabutin in lung tuberculosis treatment

The direct delivery of antibiotics to the lung has been considered an effective approach to treat pulmonary tuberculosis, which represents approximately 80% of total cases. In this sense, this work aimed at producing inhalable chitosan microparticles simultaneously associating isoniazid and rifabutin, for an application in pulmonary tuberculosis therapy. Spray-dried chitosan microparticles were obtained with adequate flow properties for deep lung delivery (aerodynamic diameter of 4 µm) and high drug association efficiencies (93% for isoniazid and 99% for rifabutin). The highest concentration of microparticles that was tested (1 mg/mL) decreased the viability of macrophage-differentiated THP-1 cells to around 60% after 24 h exposure, although no deleterious effect was observed in human alveolar epithelial (A549) cells. The release of LDH was, however, increased in both cells. Chitosan microparticles further evidenced capacity to activate macrophage-like cells, inducing cytokine secretion well above basal levels. Moreover, the propensity of macrophages to internalize microparticles was demonstrated, with uptake levels over 90%. Chitosan microparticles also inhibited bacterial growth by 96%, demonstrating that the microencapsulation preserved drug antibacterial activity in vitro. Overall, the obtained data suggest the potential of chitosan microparticles for inhalable lung tuberculosis therapy.PTDC/DTP-486 FTO/0094/2012info:eu-repo/semantics/publishedVersio

When the earth stood still: air pollution during the Covid-19 quarantine – the case of São Paulo and Rio de Janeiro

In March 2020, the World Health Organization declared a global pandemic due to the new coronavirus (COVID-19). Several countries responded to this threat by introducing quarantine measures to reduce the transmission of COVID-19 in the community. These measures have drastically reduced human activities, causing an impact on urban air pollution due to the associated reduction in automobile use and other polluting activities. We investigated this effect with measurements of Particulate Material (PM10), Carbon Monoxide (CO), Nitrogen Dioxide (NO2) and Ozone (O3), carried out by the environmental departments of the cities of São Paulo and Rio de Janeiro, for two months in 2020. We compared them with data for the corresponding months in 2019, relating to the social isolation index, measured by the Mathematics and Statistic Institute of São Paulo (IME-USP). The results show a significant decrease in NO2 and CO and an increase in O3, and little change in Particulate Material.In March 2020, the World Health Organization declared a global pandemic due to the new coronavirus (COVID-19). Several countries responded to this threat by introducing quarantine measures to reduce the transmission of COVID-19 in the community. These measures have drastically reduced human activities, causing an impact on urban air pollution due to the associated reduction in automobile use and other polluting activities. We investigated this effect with measurements of Particulate Material (PM10), Carbon Monoxide (CO), Nitrogen Dioxide (NO2) and Ozone (O3), carried out by the environmental departments of the cities of São Paulo and Rio de Janeiro, for two months in 2020. We compared them with data for the corresponding months in 2019, relating to the social isolation index, measured by the Mathematics and Statistic Institute of São Paulo (IME-USP). The results show a significant decrease in NO2 and CO and an increase in O3, and little change in Particulate Material