Angiotensin-converting enzyme inhibitor protects against cisplatin nephrotoxicity by modulating kinin B1 receptor expression and aminopeptidase P activity in mice

Cisplatin is a highly effective chemotherapeutic agent. However, its use is limited by nephrotoxicity. Enalapril is an angiotensin I-converting enzyme inhibitor used for the treatment of hypertension, mainly through the reduction of angiotensin II formation, but also through the increase of kinins half-life. Kinin B1 receptor is associated with inflammation and migration of immune cells into the injured tissue. We have previously shown that the deletion or blockage of kinin B1 and B2 receptors can attenuate cisplatin nephrotoxicity. In this study, we tested enalapril treatment as a tool to prevent cisplatin nephrotoxicity. Male C57Bl/6 mice were divided into 3 groups: control group; cisplatin (20 mg/kg i.p) group; and enalapril (1.5 mg;kg i.p) + cisplatin group. The animals were treated with a single dose of cisplatin and euthanized after 96 h. Enalapril was able to attenuate cisplatin-induced increase in creatinine and urea, and to reduce tubular injury and upregulation of apoptosis-related genes, as well as inflammatory cytokines in circulation and kidney. The upregulation of B1 receptor was blocked in enalapril + cisplatin group. Carboxypeptidase M expression, which generates B1 receptor agonists, is blunted by cisplatin + enalapril treatment. The activity of aminopeptidase P, a secondary key enzyme able to degrade kinins, is restored by enalapril treatment. These findings were confirmed in mouse renal epithelial tubular cells, in which enalaprilat (5 μM) was capable of decreasing tubular injury and inflammatory markers. We treated mouse renal epithelial tubular cells with cisplatin (100 μM), cisplatin+enalaprilat and cisplatin+enalaprilat+apstatin (10 μM). The results showed that cisplatin alone decreases cell viability, cisplatin plus enalaprilat is able to restore cell viability, and cisplatin plus enalaprilat and apstatin decreases cell viability. In the present study, we demonstrated that enalapril prevents cisplatin nephrotoxicity mainly by preventing the upregulation of B1 receptor and carboxypeptidase M and the increased concentrations of kinin peptides through aminopeptidase activity restoration

Antioxidants extraction from Pinhão (Araucaria angustifolia (Bertol.) Kuntze) coats and application to zein films

Seeds from Araucaria angustifolia (Bertol.) Kuntze are consumed after cooking and their coats discarded. Both coats and the cooking water present phenolic compounds, which may be used to improve mechanical properties and provide antioxidant characteristics to films. The objective of this work was to obtain and pinhão coat extracts and to apply these polyphenolic-rich extracts in zein films. Phenolic compounds composition, extraction yield and antioxidant activity (DPPH, ABTS and FRAP) of the extracts were determined. The most abundant molecules present in the hydroethanolic extract were (+)-catechin and an (epi)catechin dimer, whereas protocatechuic acid were predominant in the both cooking water and ethanolic extracts. Glass transition temperature of zein was not found in the extract-loaded films. Morphological changes were also caused by the presence of the extracts yielding smoother surfaces. The extracts added to zein films led to a three-fold increase in tensile strength (from 5.80 MPa to 17.65 MPa) and two-fold increase in the elongation at break (from 1.60% to 3.18%).Authors thank to CNPq (Chamada Universal– MCTI/CNPq Nº 14/ 2014, Processo 447768/2014-0), CAPES (Master's scholarship) and Fundação Araucária (Programa Universal/Pesquisa Básica e Aplicada 24/2012, protocolo 7334133700514041013) for the finantial support. Project POCI-01-0145-FEDER-006984 – Associated Laboratory LSRELCM funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT - Fundação para a Ciência e a Tecnologia and to CIMO (UID/AGR/00690/2013).info:eu-repo/semantics/publishedVersio

Superhydrophobic asphalt pavements: surface improvement

The most adverse weather condition for road safety happens when there is water, snow, or ice on the road surface because their presence highly decreases friction. Therefore, it is essential to drain or repel them quickly. If the water drops are repelled from the surface or the ice/snow formation is avoided with the application of superhydrophobic coatings, roads become safer. In order to functionalize the asphalt mixtures used in road pavements, nano/micromaterials, such as Polytetrafluoroethylene (PTFE), TiO2, and SiO2, among others have been applied by spraying coating. The mixes are usually characterized by the water contact angle, and the surface roughness is typically assessed by optical and electron analysis. This research work aims to present a brief overview of superhydrophobic asphalt mixtures

Evaluation of acute oral toxicity and diuretic activity of Rudgea viburnoides (Cham.) Benth. (congonha-de-bugre)

Rudgea viburnoides é utilizada popularmente como diurética, hipotensora, antirreumática, antissifilítica, depurativa do sangue e tratamento da dispepsia. Este trabalho teve como objetivos avaliar a toxicidade aguda e a atividade diurética do extrato etanólico bruto (EEBFRV) das folhas da R. viburnoides. Na toxicidade aguda empregou-se o teste de Classe, nas doses de 2000 e 5000 mg/kg, dose única, gavage, em camundongos Swiss e ratos Wistar (ambos os sexos). Na atividade diurética administrou-se em ratas Wistar o extrato bruto (40, 80 e 160 mg/kg, furosemida 20 mg/kg (controle +) e solução salina 0,9% (controle -). Não houve letalidade ou sinais de intoxicação, indicando baixa toxicidade desse extrato. O efeito diurético foi dose-dependente nas 24 h, com aumento dos parâmetros: volume de urina 24 h, excreção dos eletrólitos sódio, potássio e cloreto, uréia e creatinina. Os resultados até o momento, podem justificar a sua utilização popular como diurética.Rudgea viburnoides is popularly used as anti-hypertensive, anti-rheumatic, antissifilitic, blood depurative and for treatment of dyspepsia (leaves, bark, tea). The acute toxicity of ethanolic extract (EEBFRV) in single dose was performed by gavage of doses of 2000 and 5000 mg/kg in Swiss mice and Wistar rats, both sexes, by the class test. To diuretic activity in Wistar rats, it was used the EEBFRV at the doses of 40, 80 and 160 mg/kg, furosemide 20 mg/kg (control +), and saline solution 0.9 % (control -). Regarding acute toxicity, no mortality and no toxicity signs at the dose levels were observed, indicating low toxicity of the extract. The EEBFRV showed statistically significant dose-dependent diuretic effect in 24 h, increasing all parameters evaluated (24h urine volume, excretion of Na+, K+ and Cl- electrolytes, urea (BUN) and creatinine). Thus, the results so far may justify the popular use of Rudgea viburnoides as diuretic.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The Brazilian Developments On The Regional Atmospheric Modeling System (brams 5.2): An Integrated Environmental Model Tuned For Tropical Areas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)We present a new version of the Brazilian developments on the Regional Atmospheric Modeling System (BRAMS), in which different previous versions for weather, chemistry, and carbon cycle were unified in a single integrated modeling system software. This new version also has a new set of state-of-the-art physical parameterizations and greater computational parallel and memory usage efficiency. The description of the main model features includes several examples illustrating the quality of the transport scheme for scalars, radiative fluxes on surface, and model simulation of rainfall systems over South America at different spatial resolutions using a scale aware convective parameterization. Additionally, the simulation of the diurnal cycle of the convection and carbon dioxide concentration over the Amazon Basin, as well as carbon dioxide fluxes from biogenic processes over a large portion of South America, are shown. Atmospheric chemistry examples show the model performance in simulating near-surface carbon monoxide and ozone in the Amazon Basin and the megacity of Rio de Janeiro. For tracer transport and dispersion, the model capabilities to simulate the volcanic ash 3-D redistribution associated with the eruption of a Chilean volcano are demonstrated. The gain of computational efficiency is described in some detail. BRAMS has been applied for research and operational forecasting mainly in South America. Model results from the operational weather forecast of BRAMS on 5km grid spacing in the Center for Weather Forecasting and Climate Studies, INPE/Brazil, since 2013 are used to quantify the model skill of near-surface variables and rainfall. The scores show the reliability of BRAMS for the tropical and subtropical areas of South America. Requirements for keeping this modeling system competitive regarding both its functionalities and skills are discussed. Finally, we highlight the relevant contribution of this work to building a South American community of model developers. © Author(s) 2017.1011892222014/01563-1, FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo2014/01564-8, FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo2015/10206-0, FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo306340/2011-9, Conselho Nacional de Desenvolvimento Científico e TecnológicoFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq