Efeito das interacções adenosina-angiotensina II sobre a depuração renal num modelo experimental de diabetes

A nefropatia diabética é a principal causa de falência renal e, consequentemente, factor determinante de morbilidade e mortalidade relacionada com a diabetes mellitus (DM). No estado inicial da DM verifica-se hiperfiltração glomerular. A função glomerular pode ser estimada pela quantificação da taxa de filtração glomerular (GFR). A adenosina regula a GFR, modula o sistema renina-angiotensina (RAS) e o mecanismo de feedback tubuloglomerular. A actividade do RAS renal encontra-se aumentada na nefropatia diabética e contribui para a lesão progressiva da barreira de filtração glomerular. O bloqueio do RAS constitui uma abordagem terapêutica fundamental em doentes diabéticos. O efeito inibitório da adenosina sobre o RAS pode ser importante neste contexto, podendo a adenosina constituir um importante novo alvo terapêutico no contexto da nefropatia diabética. Foram objectivos deste trabalho a implementação de uma metodologia para quantificar a GFR, caracterizar os efeitos da 2-cloroadenosina (2CADO), um análogo estável da adenosina, sobre a função de renal de ratos com diabetes experimental induzida por injecção de estreptozotocina, e relacioná-los com a actividade do RAS renal. Da implementação da metodologia para quantificar a GFR, foi possível concluir que o melhor método inclui a injecção intravenosa de inulina radioactiva ou fluorescente e determinação do time-course do decaimento no plasma. A administração intraperitoneal de 2CADO aos ratos diabéticos atenuou o não aumento de peso corporal e o aumento da ingestão de comida e bebida, e da excreção de urina. Além disso, atenuou a excreção urinária de glicose e de ureia e normalizou a excreção urinária de proteínas. Os ratos diabéticos apresentaram uma excreção urinária da angiotensinogéneo superior à dos ratos controlo e a 2CADO não alterou este resultado. Os resultados com a 2CADO demonstram a sua influência benéfica na nefropatia diabética. Estes efeitos da 2CADO podem estar relacionados com a capacidade para baixar a glicemia e melhorar a resistência à insulina mas também com efeitos renais directos e indirectos. São necessários, no entanto, estudos mais aprofundados para avaliar se a interacção adenosina/Ang II participa nesta renoprotecção indirecta.Diabetic nephropathy is the main cause for end-stage renal disease and, consequently, a determinant factor to morbidity and mortality related to diabetes mellitus (DM). Initially, DM is characterized by glomerular hyperfiltration. Glomerular function can be estimated by quantification of glomerular filtration rate (GFR). Adenosine regulates GFR, modulates the renin-angiotensin system (RAS) and the tubuloglomerular feedback. Renal RAS activity is enhanced in diabetic nephropathy and contributes to impairment of glomerular filtration barrier. Pharmacological agents that inhibit RAS have been recommended to diabetic patients. Adenosine inhibitory effect of RAS can be important in this context as a new therapeutical target in diabetic nephropathy. The aims of these study were to implement a new method for GFR quantification and to characterize the effects of 2-chloroadenosin (2CADO), a stable and non-metabolized analogue of adenosine, in renal function of estreptozotocininduced diabetic rats and relate them with renal RAS activity. Our results show that the most accurate way to quantify GFR is to inject radioactive or fluorescent inulin, intravenously, and follow plasma decay time-course. The intraperitoneal administration of 2CADO, to estreptozotocin-induced diabetic rats, attenuates the arrest of body weight, and food and water intake, and urine excretion. Furthermore, it attenuates the urinary excretion of glucose and urea and normalizes protein excretion. Estreptozotocin-induced diabetic rats excreted more angiotensinogen than control rats, and 2CADO administration did not change these result. Taken together, the results express the beneficial effect of 2CADO in diabetic nephropathy. 2CADO effects may be related to the capacity to improve glicemia and insulin resistance, but also with direct and indirect renal effects. Further studies are required to evaluate if the adenosine/angiotensin II interaction participates in these indirect renoprotection

Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure Control

This is the author accepted manuscript. The final version is available from Frontiers Media via the DOI in this record.Oxygen sensing mechanisms are vital for homeostasis and survival. When oxygen levels are too low (hypoxia), blood flow has to be increased, metabolism reduced, or a combination of both, to counteract tissue damage. These adjustments are regulated by local, humoral or neural reflex mechanisms. The kidney and the carotid body are both directly sensitive to falls in the partial pressure of oxygen and trigger reflex adjustments and thus act as oxygen sensors. We hypothesize a cooperative oxygen sensing function by both the kidney and carotid body to ensure maintenance of whole body blood flow and tissue oxygen homeostasis. Under pathological conditions of severe or prolonged tissue hypoxia, these sensors may become excessively activated continuously and increase perfusion pressure chronically. Consequently, persistence of their activity could become a driver for the development of hypertension and cardiovascular disease. Hypoxia-mediated renal and carotid body afferent signaling triggers unrestrained activation of the renin angiotensin-aldosterone system (RAAS). Renal and carotid body mediated responses in arterial pressure appear to be synergistic as interruption of either afferent source has a summative effect of reducing blood pressure in renovascular hypertension. We discuss that this cooperative oxygen sensing system can activate/sensitize their own afferent transduction mechanisms via interactions between the RAAS, hypoxia inducible factor and erythropoiesis pathways. This joint mechanism supports our view point that the development of cardiovascular disease involves afferent nerve activation.This work was supported by the British Heart Foundation (FS/14/2/30630, RG/12/6/29670 and PG/15/68/31717) and the European Union, Seventh Framework Programme, Marie Curie Actions (CARPEDIEM - No 612280)

“Conta-me uma história”: Dinamização da hora do conto: recursos auxiliares de histórias

Relatório de Prática Profissional Supervisionada apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre em Educação Pré-EscolarO presente relatório é o culminar do processo vivenciado ao longo da Prática Profissional Supervisionada, que decorreu no último semestre do Mestrado em Educação Pré-Escolar, em contexto de jardim de infância. Através do mesmo procura-se ilustrar e fundamentar, de um modo reflexivo e crítico, todo o trajeto realizado durante esse percurso. Para o trabalho desenvolvido tive em consideração as intenções que delineei para a ação pedagógica, mais concretamente, para o grupo de crianças em questão e respetivas famílias e para toda a equipa educativa. Tomando como ponto de partida as observações diárias e a caracterização do contexto, constatei: i) o interesse do grupo de crianças por histórias; ii) o facto da “Hora do Conto” constar no plano diário, mas não ser uma prática regular; iii) o livro enquanto único recurso neste momento. A par do referido, a temática da dinamização da “Hora do Conto” foi algo que suscitou o meu interesse. Assim sendo, ao longo deste relatório irei apresentar a problemática: “Conta-me uma história” – dinamização da hora do conto: recursos auxiliares de histórias, problemática na qual se focalizou o processo investigativo desenvolvido. Para um desenvolvimento proficiente da investigação e com o intuito de recolher informações pertinentes, recorri a diversas fontes: (i) notas de campo fruto da observação; (ii) entrevista semiestruturada à educadora; (iii) inquéritos por questionário realizados às crianças e suas famílias; (iv) registos fotográficos. Concluindo, os resultados alcançados apontam para a importância das histórias para as crianças e dos benefícios de estas explorarem e manipularem os recursos auxiliares de histórias e, também, para a influência do meio familiar no interesse das crianças pelo conto de histórias.ABSTRACT This report is the culmination of the experienced process during the Supervised Professional Practice, which took place in the last semester of the Master’s Degree in Pre-School Education, in a kindergarten context. Through the same, it is tried to illustrate and to base, in a reflexive and critical way, all the path realized during that route. For the work developed I considered the intentions that I outlined for the pedagogical action, more concretely, for that group of children and their families and for the whole educational team. Taking as starting point the daily observations and the characterization of the context, I noticed: i) the interest of the group of children for stories; ii) the fact that the “Story Time” appears on a daily basis, but not be a regular practice; iii) the book as the only resource at this time. In addition to the above, the thematic of the dynamization of the “Story Time” was something that aroused my interest.Therefore, throughout this report I will present the problematic: “Tell me a story” – dynamization of the story time: auxiliary resources of stories, problematic in which the research process was focused. For a proficient development of the investigation and with the intention of collecting pertinent information, I resorted for diverse sources: (i) field notes fruit of the observation; (ii) semi-structured interview with the educator; (iii) questionnaire surveys approached to children and their families; (iv) photographic records. In conclusion, the results achieved point to the importance of stories for children and the benefits of them to explore and manipulate the auxiliary resources of stories and, as well, the influence of the family environment on children’s interest in tale of stories.N/

Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure Control

Oxygen sensing mechanisms are vital for homeostasis and survival. When oxygen levels are too low (hypoxia), blood flow has to be increased, metabolism reduced, or a combination of both, to counteract tissue damage. These adjustments are regulated by local, humoral, or neural reflex mechanisms. The kidney and the carotid body are both directly sensitive to falls in the partial pressure of oxygen and trigger reflex adjustments and thus act as oxygen sensors. We hypothesize a cooperative oxygen sensing function by both the kidney and carotid body to ensure maintenance of whole body blood flow and tissue oxygen homeostasis. Under pathological conditions of severe or prolonged tissue hypoxia, these sensors may become continuously excessively activated and increase perfusion pressure chronically. Consequently, persistence of their activity could become a driver for the development of hypertension and cardiovascular disease. Hypoxia-mediated renal and carotid body afferent signaling triggers unrestrained activation of the renin angiotensin-aldosterone system (RAAS). Renal and carotid body mediated responses in arterial pressure appear to be synergistic as interruption of either afferent source has a summative effect of reducing blood pressure in renovascular hypertension. We discuss that this cooperative oxygen sensing system can activate/sensitize their own afferent transduction mechanisms via interactions between the RAAS, hypoxia inducible factor and erythropoiesis pathways. This joint mechanism supports our view point that the development of cardiovascular disease involves afferent nerve activation

Comparative assessment of FRP´S and steel bars applied on the reinforcement of concrete structures

Nowadays the sustainability of construction and the need for more sustainable construction solutions is one big concern in the construction field. This way, many times the FRP reinforcing materials are seen and sold as more sustainable and ecological options, when compared with steel or other metal based materials. This fact is essentially due to their non carbon dioxide corrosion characteristics that ensure longer service life and light-weight combined with high strength (Waldron, 2004). But the application of FRP bars for concrete reinforcement is a very specific application that deals with very different requirements and conditions. Due to that, the sustainability has to be assessed through the whole range of structural applications by specific tools, able to evaluate the real sustainability such as the Life Cycle Assessment (LCA) tools (Franzoni, 2011). To address this issue, a comparative study has been performed , among different concrete reinforcing materials such as steel, Glass fiber-reinforced Polymer (GFRP), Aramid fiberreinforced polymer (AFRP) and Carbon Fiber-reinforced Polymer(CFRP) and for two different structural applications: beam and slab. Therefore, the objective of this work is to compare the LCA of concrete structural elements, under the same ultimate and service load conditions, reinforced by steel and different FRPs

Diabetes downregulates renal adenosine A2A receptors in an experimental model of hypertension.

Studies on diabetic nephropathy rarely take into account that the co-existence of diabetes and hypertension is frequent and further aggravates the prognosis of renal dysfunction. Adenosine can activate four subtypes of adenosine receptors (A1, A2A, A2B and A3) and has been implicated in diabetic nephropathy. However, it is not known if, in hypertensive conditions, diabetes alters the presence/distribution profile of renal adenosine receptors. The aim of this work was to describe the presence/distribution profile of the four adenosine receptors in six renal structures (superficial/deep glomeruli, proximal/distal tubules, loop of Henle, collecting tubule) of the hypertensive kidney and to evaluate whether it is altered by diabetes. Immunoreactivities against the adenosine receptors were analyzed in six renal structures from spontaneously hypertensive rats (SHR, the control group) and from SHR rats with diabetes induced by streptozotocyin (SHR-STZ group). Data showed, for the first time, that all adenosine receptors were present in the kidney of SHR rats, although the distribution pattern was specific for each adenosine receptor subtype. Also, induction of diabetes in the SHR was associated with downregulation of adenosine A2A receptors, which might be relevant for the development of hypertensive diabetic nephropathy. This study highlights the adenosine A2A receptors as a potential target to explore to prevent and/or treat early diabetes-induced hyperfiltration, at least in hypertensive conditions

High Levels of Heavy Metal(loid)s Related to Biliary Hyperplasia in Hedgehogs (<i>Erinaceus europaeus</i>)

Heavy metal(loid) pollution of ecosystems is a current One Health problem. The liver is one of the most affected organs in cases of acute or chronic exposure to abnormal amounts of these substances, inducing histopathologic lesions. In order to assess the influence of heavy metal(loids), forty-five European hedgehogs (Erinaceus europaeus) were submitted to necropsy, and liver samples were collected for a routine histopathology exam and metal(loid)s determination (As, Cd, Co, Cr, Cu and Pb) by ICP-MS. Age was estimated during the necropsy exam. Biliary hyperplasia was the most frequent lesion observed (16/45; 35.56%). No statistically significant associations were found between biliary hyperplasia and age or sex. Metal(loid)s’ concentrations were higher in animals with biliary hyperplasia (except for As). There was a statistically significant difference for both Cd and Co. For As, Cd and Co, cubs and juveniles animals showed significantly lower concentrations than elder individuals. Only for Pb were significant differences found between females and males. As described in the literature, exposure to metal(loid)s may be a cause of biliary hyperplasia, although further research (including the use of biochemical methods) is needed to support these results. To the authors’ knowledge, this is the first report of this association in hedgehogs

Biliary hyperplasia and metal(loid)s exposure in hedgehogs (Erinaceus europaeus)

Objectives: E. europaeus has been used as a sentinel of different One Health concerns, including heavy metal(loid)s pollution or zoonotic pathogens. This work aims to study trace elements’ health effects, performing a toxicology and histopathology assessment with hedgehogs. Materials and Methods: Forty-six hedgehogs from three Portuguese rescue centres (CERVAS, LxCRAS and RIAS) were submitted to necropsy. Sex and age group were visually estimated. A liver sample was stored in a 10% formalin container for histopathology routine examination. Another liver portion was collected into a zip bag and stored under -20ºC. Then, it was completely freeze-dried for two days at -56ºC (LaboGene CoolSafe®) and stored frozen until further analysis. Acid digestion was performed in a digestion plate (DigiPrep-MS®) and metal(loid)s concentrations (As, Cd, Cr, Cu, and Pb) was determined with inductively coupled plasma mass spectrophotometry (ICP-MS). Results: High levels of Cu were found in the liver (35.66 ± 19.65 mg kg-1 dry weight [dw]), with some animals passing 100 mg kg-1 dw, which is a consistently high value for insectivores. Biliary hyperplasia was the most frequent lesion observed, in 36% of the analyzed livers. Animals presenting biliary hyperplasia show higher levels of metal(loid)s (with the exception of As), with a significant difference for Cd (p=0.007) and Co (p=0.019). No statistically significant associations were found between biliary hyperplasia and age or sex. Conclusions: Exposure to metal(loid)s may be a cause of biliary hyperplasia, though other analyses (including the use of biochemistry methods) are needed to confirm this hypothesis. To the authors’ knowledge, this was the first report of this association in hedgehogs. Further research (including different organs and locations) is crucial to understand the impact of metal(loid)s pollution in Portugal. &nbsp; Keywords: environmental contamination; hedgehog; One Health; trace elements. &nbsp; &nbsp; Funding This work was funded by FCT (Fundação para a Ciência e Tecnologia) under the phD scholarship 2021.04520.BD. Teresa Letra Mateus was supported by UIDB/CVT/00772/2020 and LA/P/0059/2020 funded by FCT