Histopathological Evaluation of Combined Impacts of the Synthetic Progestin Levonorgestrel and Temperature on the Female Zebrafish Maturation Using a Semi-quantitative Grading Analysis—Is it Enough?

Pharmaceuticals contamination (e.g., synthetic progestins), and global climate change, represent two of the most stressful factors affecting aquatic species. To our knowledge, there is huge gap of data regarding the combined effects of both stressors on vertebrates’ reproduction. Thus, it is crucial to implement rapid screenings of measurable histopathological alterations in fish gonads. For that, we propose: (1) an evaluation of the combined effects of progestin (levonorgestrel) and temperature on maturation of zebrafish female gonads, using a semi-quantitative method (i.e., grading) and (2) testing the robustness of the grading analysis comparatively to a quantitative method (i.e., stereology). Grading analysis showed a decrease on maturation stage of ovaries exposed to both stressors. Although grading is less robust than stereological analysis, it is recommended for a preliminary approach, since it gives a correct idea on trends and it is fast and cost-effective. For a detailed histological assessment, we recommend a stereological study.     

Spray-dried fucoidan microparticles for pulmonary delivery of antitubercular drugs

Pulmonary tuberculosis accounts for 80% of cases and the delivery of antitubercular drugs into the lungs allows targeting the infected organ and, possibly, reducing systemic drug toxicity. This work aimed at using fucoidan as matrix of inhalable microparticles that associate two first-line antitubercular drugs, for an application in pulmonary tuberculosis therapy. Fucoidan is composed of fucose and sulphated sugar residues, moieties described as being recognised by surface receptors of alveolar macrophages, which host mycobacteria. Inhalable fucoidan microparticles loaded with antitubercular drugs were successfully produced with high association efficiencies of either isoniazid (95%) or rifabutin (81%). The microparticles evidenced no cytotoxicity on lung epithelial cells (A549). However, rifabutin-loaded microparticles showed a certain degree of toxicity on macrophage-like cells (THP-1) at the highest tested concentration (1?mg/mL). Furthermore, microparticles showed favourable aerodynamic properties for deep lung delivery (MMAD 2.0–3.8?µm) and, thus, show potential for an application as inhalable tuberculosis therapy.     

Antiangiogenic evaluation of ZnWO4 nanoparticles synthesised through microwave-assisted hydrothermal method

Angiogenesis, the complex process of formation of new blood vessels from pre-existing blood vessels, which involves the participation of several pro- and anti-angiogenic factors, is implicated in many physiological and pathological conditions. Nanoparticle-based anti-angiogenic activity at the tumour tissue, harnessed by the Enhanced Permeability and Retention Effect (EPR effect), could potentially become a breakthrough therapy to halt tumour progression. Herein, we evaluate the anti-angiogenic effect of ZnWO₄ nanoparticles (NPs). The nanoparticles were obtained by microwave-assisted hydrothermal synthesis (MAHS) at 120?°C for 60?min and were structurally characterised by X-ray diffraction (XRD) and micro-Raman (MR) spectroscopy. The mean size and polydispersity index were estimated by Zeta potential analysis. The XRD analysis revealed structural organisation at a long-range order, with an average crystallite size of around 3.67?nm, while MR revealed short-range order for ZnWO₄. The anti-angiogenic potential of zinc tungstate nanoparticles was investigated through the chorioallantoic membrane assay (CAM) using fertilised chicken eggs. We demonstrate, in an unprecedented way, that nanocrystalline ZnWO₄ NPs obtained by MAHS, at low reaction temperatures, showed excellent anti-angiogenic properties even at low concentrations. The ZnWO₄ NPs were further evaluated for its cytotoxicity in vitro.     

Responses of human hepatoma HepG2 cells to silver nanoparticles and polycyclic aromatic hydrocarbons

The nanotechnology has revolutionized the global market with silver nanoparticles (AgNP) occupying a prominent position due to their remarkable anti-bacterial properties. However, there is no data about the adverse and toxic effects of associations of AgNP and ubiquitous compounds, such as polycyclic aromatic hydrocarbons (PAH). In the current study, we investigated the responses of HepG2 cells to realistic concentrations of AgNP (0.09, 0.9, and 9?ng ml^?1) and mixture of PAH (30 and 300?ng ml^?1), separately and in association. Cell viability and cytotoxicity (neutral red retention and MTT production assays) and proliferation (crystal violet [CV] assay), xenobiotic efflux transporter activity (rhodamine B accumulation assay), ROS levels (dichlorodihydrofluorescein diacetate assay), and lipid peroxidation (pyrenylphosphine-1-diphenyl assay) were analyzed. There was no decreases of cell viability after exposure to AgNP, PAH and most of AgNP?+?PAH associations, but increases of cell viability/number (CV assay) occurred. Efflux transporter activity was not affected, with exception of one AgNP?+?PAH associations, ROS levels increased, but lipid peroxidation decreased. Some toxicological interactions occurred, particularly for the highest concentrations of AgNP and PAH, but there is no evidence that these interactions increased the toxicity of AgNP and PAH.     

Low weight at birth and unfavorable socioeconomic background: effects on language and fluid intelligence

Low birthweight (<2500 g), associated with low socioeconomic status, has a negative effect on cognition and development. This is especially true for fluid intelligence and language. This study aimed to examine and identify (1) fluid intelligence and language in low- and adequate-birthweight children in a low-income Brazilian neighborhood and (2) the environmental factors that could account for potential group differences. There were 100 children participated in the study, of whom 53 had low birthweight and 47 had adequate birthweight. The children completed a battery of tests for fluid cognition and language. Their socioeconomic background and home environment were explored through a caregiver questionnaire. The results indicated significant group differences in fluid intelligence but not in language. Environmental factors partially explained the results. The variables ‘years of preschool’ and ‘number of learning games/books’ predicted better test results. Furthermore, the children underperformed in naming speed but not in accuracy, and the low-birthweight children also underperformed in fluid intelligence. It is concluded that environmental factors affect both birthweight groups and may compromise child development.     

The erythrocyte alloimmunisation in patients with sickle cell anaemia: a systematic review

Transfusion therapy is a common practice in the treatment of anaemia and can cause erythrocyte alloimmunisation. To systematise data related to erythrocyte alloimmunisation in patients with sickle cell disease (SCD), a bibliographic search was carried out in September 2017 to search for studies in four electronic databases. (i) Referring to the original work, (ii) being cohort or case–control, (iii) having been developed with individuals with SCD and (iv) having evaluated the erythrocyte alloimmunisation. Two reviewers identified the articles for inclusion in the study, extracted the predetermined data and carried out the evaluation of the methodological quality of the work. 21 studies were selected; the studies included data on 20 636 individuals (children and adults), were mostly published in the last 10 years, were developed in the United States and had high methodological quality. The occurrence of erythrocyte alloimmunisation ranged from 4·4 to 76%, and there was a higher rate of alloimmunisation against antigens of the Rh system. The risk factors for alloimmunisation were age; gender (female); red blood cell (RBC) units received; presence of ≥1 autoantibodies, TNF‐α, interleukin (IL1B), human leukocyte antigens (HLA)‐DRB1 gene polymorphisms; first blood transfusion (BT) after 5 years of age, transfusion episodic, multiple or during inflammatory events, acute chest syndrome (ACS) and vase‐occlusive crisis (VOC); increased percentage of CD41 T memory cells; and positive direct antiglobulin test. Transfusion policies should be developed to protect the patient and his or her health based on the main factors associated with its incidence.