Role of central autonomic network nuclei on the generation of sympathetic tonus in essential hypertension : an exploratory study in conscious rats

Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2015Um dos principais contributos para o aparecimento, desenvolvimento e manutenção da hipertensão arterial é a existência e persistência de uma atividade simpática elevada. Dados de modelos experimentais de hipertensão e doentes hipertensos tornaram evidente que a simpatoexcitação excessiva, característica da hipertensão, é deletéria resultando em danos nos órgãos periféricos e aumento da morbilidade e mortalidade. Assim, a identificação da origem desta simpatoexcitação é crucial por forma a serem desenvolvidas novas intervenções terapêuticas. No entanto, até ao momento, os mecanismos exatos responsáveis pela ativação simpática na hipertensão arterial permanecem por elucidar, devido à sua complexidade e origem multifatorial. A face rostroventrolateral do bulbo (FRVLB) é uma área bulbar simpatoexcitatória pertencente à rede autonómica central, que desempenha um papel importante na fisiopatologia da hipertensão arterial. Em termos fisiológicos, a FRVLB tem um papel fundamental na geração do tónus simpático periférico. Os seus neurónios projetam-se monosinapticamente para os neurónios simpáticos pré-ganglionares do núcleo de células da coluna intermediolateral da medula espinhal, condicionando o tónus simpático periférico para o coração e vasos. O núcleo parabraquial lateral (NPL) e a substância cinzenta periaqueductal (SCP) são outras áreas da rede autonómica central que podem estar envolvidas na geração da atividade simpática. O NPL tem um papel crítico na transmissão central de sinais do tronco cerebral relacionados com a regulação de fluidos e ingestão de eletrólitos e com a função cardiovascular, em particular aqueles que regulam a pressão arterial em resposta à hemorragia e à hipovolémia. As colunas da SCP são capazes de modular as funções cardíacas simpáticas através de uma variedade de vias indiretas que envolvem neurónios pré-motores simpáticos encontrados em locais específicos do hipotálamo, mesencéfalo, protuberância e bulbo raquidiano. No presente trabalho, de natureza exploratória, procurámos estabelecer as consequências funcionais no tónus simpático e pressão arterial decorrentes da diminuição da excitabilidade da FRVLB e NPL e SCP em duas situações, em normotensão e em hipertensão, respetivamente. Para tal, e em cada área central de estudo, os valores da pressão arterial, output autonómico, função baro- e quimiorreceptora foram monitorizados e os parâmetros metabólicos e comportamentais avaliados antes e depois da microinjeção do lentivírus com informação genética que codifica os canais hKir2.1. Os resultados mostraram que a microinjeção de LVV-hKir2.1 na FRVLB de ratos normotensos provocou uma descida significativa do tónus simpático, embora esta não se tenha refletido na pressão arterial sistólica, diastólica e média. Adicionalmente, não se observaram efeitos sobre os reflexos cardiorrespiratórios, parâmetros metabólicos e atividade locomotora/exploratória. Aos 60 dias após a microinjeção lentiviral no NPL de ratos hipertensos, o tónus simpático diminuiu significativamente refletindo-se nos valores de pressão arterial e frequência cardíaca. Verificou-se também uma tendência para a diminuição da variação do reflexo quimiorreceptor; no entanto, não houve neste caso significância estatística. Além disso, o silenciamento da SCP em ratos hipertensos não teve repercussões na pressão arterial, frequência cardíaca e tónus simpático, mas o ganho do barorreflexo diminuiu. O núcleo Kolliker-Fuse, localizado na protuberância e responsável pelo controlo pôntico da respiração foi utilizado como núcleo controlo para as duas últimas áreas. Assim, com este trabalho mostramos a suposta contribuição das áreas do mesencéfalo e da rede autonómica central pôntica para a etiologia da hipertensão de causa neurogénica e fornecemos pistas para possíveis futuras intervenções terapêuticas no controlo da simpatoexcitação a nível central.Sympathetic nervous system hyperactivity is a major contributor to the onset, development and maintenance of essential arterial hypertension. Taking into account data from experimental models of hypertension and from hypertensive patients, it is evident that the excessive sympathoexcitation that characterizes hypertension is deleterious leading to organ damage and increasing morbidity and mortality. Thus, is essential to identify the origin of the sympathoexcitation in order to develop new therapeutic interventions. However, until the moment, the precise mechanisms responsible for the sympathetic activation in essential hypertension remain to be elucidated, since they are complex and multifactorial. The rostral ventrolateral medulla (RVLM) is a medullar sympathoexcitatory area of the central autonomic network, which plays a crucial role in essential hypertension pathophysiology. Physiologically, RVLM has a key role in peripheral sympathetic tone generation. Its neurons monosynaptically project to the sympathetic preganglionic ones in the intermediolateral column of the spinal cord, conditioning peripheral sympathetic tone to the heart and vessels. Other areas of the central autonomic network that could also be involved in the generation of sympathetic activity are the lateral parabrachial nucleus (LPBN) and the periaqueductal gray matter (PAG). LPBN plays a critical role in relaying signals related to the regulation of fluid and electrolyte intake and cardiovascular function from the brainstem to the forebrain, in particular those regulating blood pressure in response to hemorrhages and hypovolemia. PAG columns are capable of modulating cardiac sympathetic functions through a series of indirect pathways involving sympathetic premotor neurons found in specific sites of the hypothalamus, midbrain, pons and medulla oblongata. In the present work, of exploratory nature, we sought to establish the functional consequences on sympathetic tone and arterial blood pressure of decreasing the excitability of RVLM and LPBN and PAG in normotension and hypertension, respectively. For that, blood pressure, autonomic output, circadian blood pressure, baro and chemoreceptor function were monitored and metabolic plus behavioral parameters evaluated before and after microinjection in each area of genetic information encoding hKir2.1 channels through a lentivirus. Results show that LVV-hKir2.1 microinjection into the RVLM of normotensive rats promoted a significant decrease in sympathetic tone, however it did not affect systolic, diastolic and mean blood pressure values. Additionally, no deleterious effects on cardiorespiratory reflexes, metabolic parameters and locomotor plus exploratory activity were observed. In hypertensive conditions, 60 days post lentiviral microinjection into the LPBN, sympathetic outflow decreased significantly and reflect itself on blood pressure and heart rate values as well. A tendency towards chemoreflex variation attenuation was also observed, however statistical significance was not attained. In addition, PAG silencing had no repercussions on arterial blood pressure, heart rate and sympathetic tone but decreased cardiac baroreflex gain. Has a control area for these functional modifications on physiological parameters, we also microinjected the lentiviral vector at the Kolliker –Fuse nucleus, a pontine nucleus which controls respiration. Hence, with this exploratory work we unravelled the putative contribution of areas of the midbrain and pontine central autonomic network for the etiology of neurogenic hypertension and provide clues to possible future therapeutic interventions to control sympathoexcitation

Estudo da influência das concentrações de N e P sobre o desenvolvimento de cianobactérias em cultura mista

Ao longo de 40 anos, muitos trabalhos têm vindo a ser desenvolvidos no âmbito do tema da eutrofização e desenvolvimento de biomassa fitoplanctónica. Em todos eles, eram sugeridos factores responsáveis, desde a latitude, luz, temperatura, mistura da coluna de água e os inputs de nutrientes. Toda a controvérsia gerada em torno da eutrofização, levou a que a inércia adoptada em situações de risco induzisse a degradação de muitos sistemas aquáticos. É quando, além da degradação estética, os problemas começam a surgir, que se compreende a necessidade de que surjam medidas de gestão e requalificação das lagoas e bacias hidrográficas. A tendência para a ocorrência de florescências de organismos como cianobactérias, implica a necessidade de maiores cuidados nos usos das massas de água, principalmente ao nível da produção de água para consumo humano e do uso recreativo. Uma boa gestão, implica um conhecimento aprofundado do comportamento destes organismos. Este trabalho, apresenta as respostas de organismos recolhidos em florescências naturais, na Lagoa das Furnas – ilha de S. Miguel (Açores) em meios com diferentes teores de azoto. As diferenças entre os resultados, permitem retirar algumas conclusões sobre as condições preferenciais ao seu desenvolvimento. De um modo geral, as culturas comportaram-se da forma esperada, desenvolvendo-se mais com doses de azoto mais elevadas. Este desenvolvimento foi verificado tanto pelo aumento das partículas ao longo de todo o ensaio, mas também pelos valores de pigmentos registados no fim deste. Por outro lado, o facto do azoto ter sido adicionado sob a forma amoniacal ou de nitratos, permite concluir que os organismos presentes nas florescências preferem assimilar as formas azotadas que impliquem um menor consumo energético. Daí que se tenham verificado desenvolvimentos mais significativos em meios em que foi adicionado azoto amoniacal. O facto de ser tratar de um trabalho baseado nas condições de desenvolvimento de organismos vivos, era de esperar alguma imprevisibilidade dos comportamentos. Sendo assim, será recomendável aprofundar o conhecimento das reacções dos organismos em cultura mista para doses diferentes de azoto, assim como a realização de ensaios em que para uma dose de N fixa, se façam variar as concentrações de P

O continuum entre "contribuir para" e estar "diretamente ligado a" impactos adversos nos Direitos Humanos, no contexto do setor bancário

Over the past few years, we have been observing the effects of globalization. Companies have grown tremendously, both in economic power and political influence, operating increasingly on a global scale, through a complex network of customers and entities. This growth not only has the potential to accelerate the economic and social development of several geographies around the world, especially the less developed ones, but can lead, on the other hand, to a great disregard for Human Rights. In fact, with the opening of borders for companies that continue to prioritize profit maximization, we are also witnessing an increasing fragmentation in production, with companies seeking to produce in poorer countries based on the comparative advantages offered in each of these locations. The Human Rights not only of the communities where these companies are located, but also of their workers and even consumers, as well as the environment itself, are put on the back burner. However, the responsibility to respect Human Rights should not only be shared between States and Companies, since the financial sector is also essential to avoid violations of these rights. Thus, the emergence of more and more serious adverse impacts on people and the environment have triggered the creation of soft law instruments, applicable to States, Companies and Banks, regarding Human Rights issues. Therefore, this dissertation aims to analyze the responsibility of these actors regarding Human Rights issues, as well as the different ways to overcome their involvement in adverse impacts to these rights. In addition, we reflected on the voluntary nature of the existing international instruments for these matters, which leads many of these actors to continue to disregard Human Rights in their activities, highlighting the urgent need to create a legal framework on Human Rights, applicable both to companies and to the financial sector.Ao longo dos últimos anos, temos vindo a observar os efeitos da globalização. As Empresas têm vindo a crescer extraordinariamente, tanto em poder económico, como influência política, operando, cada vez mais, a uma escala global, através de uma rede complexa de clientes e entidades. Este crescimento tem o potencial para acelerar o desenvolvimento económico e social de várias geografias por todo o mundo, especialmente as menos desenvolvidas, mas, por outro lado, pode também levar a uma grande desconsideração pelos Direitos Humanos. De facto, com a abertura das fronteiras para as Empresas, que, em muitos casos, continuam a priorizar a maximização dos lucros, assiste-se, também, a uma fragmentação crescente na produção, com Empresas a procurarem produzir em países mais pobres, com base nas vantagens comparativas oferecidas em cada uma destas localizações. Os Direitos Humanos, tanto das comunidades onde estas Empresas se localizam, mas também dos seus trabalhadores e, até, dos consumidores, bem como o próprio meio ambiente são colocados em segundo plano. No entanto, a responsabilidade pelos Direitos Humanos não deve ser só repartida entre Estados e Empresas, uma vez que o setor financeiro também é essencial para que se evitem violações a estes direitos. Assim, o surgimento de mais e mais gravosos impactos adversos a pessoas e ao meio ambiente despoletaram a criação de instrumentos de soft law, aplicáveis a Estados, Empresas e Bancos, sobre as questões de Direitos Humanos. Neste sentido, na presente Dissertação analisou-se a responsabilidade destes atores no que concerne a questões de Direitos Humanos, bem como as diferentes maneiras para ultrapassar os seus envolvimentos em impactos adversos a esses direitos. Para além disto, refletiu-se sobre o caráter voluntário dos instrumentos internacionais existentes para estas matérias, que leva a que muitos destes atores continue a desconsiderar os Direitos Humanos nas suas atividades, exaltando-se a necessidade urgente de criação de um quadro legal em matéria de Direitos Humanos, aplicável tanto para as Empresas, como para o Setor Financeiro

Intensificação do Trabalho dos Diretores Escolares de Salvador e Região Metropolitana

Ao investigar de que maneira ocorre a intensificação do trabalho dos (as) diretores (as) das escolas de Ensino Médio da Bahia, o artigo analisa os efeitos das transformações dos sentidos do trabalho na sociedade contemporânea e a introdução dos parâmetros da Nova Gestão Pública na educação. A partir da análise do marco legal e de entrevistas com os profissionais foi possível apontar como parte dos elementos desse processo:  a) maior centralização das decisões em detrimento da gestão democrática e; b) a naturalização do acúmulo e diversidade das tarefas.

Increased lung inflammation with oxygen supplementation in tracheotomized spontaneously breathing rabbits: an experimental prospective randomized study

Background Mechanical ventilation is a well–known trigger for lung inflammation. Research focuses on tidal volume reduction to prevent ventilator-induced lung injury. Mechanical ventilation is usually applied with higher than physiological oxygen fractions. The purpose of this study was to investigate the after effect of oxygen supplementation during a spontaneous ventilation set up, in order to avoid the inflammatory response linked to mechanical ventilation. Methods A prospective randomised study using New Zealand rabbits in a university research laboratory was carried out. Rabbits (n = 20) were randomly assigned to 4 groups (n = 5 each group). Groups 1 and 2 were submitted to 0.5 L/min oxygen supplementation, for 20 or 75 minutes, respectively; groups 3 and 4 were left at room air for 20 or 75 minutes. Ketamine/xylazine was administered for induction and maintenance of anaesthesia. Lungs were obtained for histological examination in light microscopy. Results All animals survived the complete experiment. Procedure duration did not influence the degree of inflammatory response. The hyperoxic environment was confirmed by blood gas analyses in animals that were subjected to oxygen supplementation, and was accompanied with lower mean respiratory rates. The non-oxygen supplemented group had lower mean oxygen arterial partial pressures and higher mean respiratory rates during the procedure. All animals showed some inflammatory lung response. However, rabbits submitted to oxygen supplementation showed significant more lung inflammation (Odds ratio = 16), characterized by more infiltrates and with higher cell counts; the acute inflammatory response cells was mainly constituted by eosinophils and neutrophils, with a relative proportion of 80 to 20% respectively. This cellular observation in lung tissue did not correlate with a similar increase in peripheral blood analysis. Conclusions Oxygen supplementation in spontaneous breathing is associated with an increased inflammatory response when compared to breathing normal room air. This inflammatory response was mainly constituted with polymorphonuclear cells (eosinophils and neutrophils). As confirmed in all animals by peripheral blood analyses, the eosinophilic inflammatory response was a local organ event

Oxygen Increases Lung Inflammatory Response in Spontaneous One-Lung Ventilation in Rabbits: A Prospective Randomized Experimental Study

Study objective: The purpose of this study was to investigate if oxygen supplementation would increase lung inflammatory response in a spontaneous one-lung ventilation animal model, when compared to room-air oxygen fraction. Design: In vivo prospective randomized animal study Setting: University research laboratory Subjects: New Zealand rabbits Interventions: Rabbits (n=20) were randomly assigned to 2 groups (n=10 each group). Groups (OS – Oxygen Supplemented, and NOS – Non-Oxygen Supplemented) were submitted to spontaneous One-Lung Ventilation (OLV) during 60 minutes; OS group had a 2-liter/minute oxygen supplement, and NOS group was kept on roomair. Ketamine/xylazine was administered for induction and maintenance of anesthesia. One-lung ventilation was achieved by administration of air into interpleural space, and left lung collapse was visually confirmed through the center of diaphragm. Clinical monitoring and arterial blood gas analyses were performed in all rabbits. Measurements: Lung histology plates were observed under light microscopy for quantification of inflammatory response (light, moderate and severe). Main results: All subjects had at least light inflammatory response. However, rabbits submitted to oxygen supplementation had a statistically significant value for the occurrence of moderate inflammation (p<0.001). The inflammatory cells found were mainly eosinophils and neutrophils in an average proportion of 80/20. Oxygen partial pressure increased in both groups with a higher proportion in OS group (p<0.001). Conclusion: In this spontaneous OLV model, the use of oxygen supplementation was associated with a greater inflammatory response.info:eu-repo/semantics/publishedVersio

Spontaneous one-lung ventilation increases the lung inflammatory response : an experimental pilot study

Study objective: The purpose of this study was to investigate if spontaneous one-lung ventilation would induce any type of inflammatory lung response when compared to spontaneous two-lung ventilation and its intensity, by quantification of inflammatory cells in lung histology at the end of the procedure. Design: In vivo prospective randomised animal study Setting: University research laboratory Subjects: New Zealand rabbits Interventions: Rabbits (n=20) were randomly assigned to 4 groups (n=5 each group). Groups 1 and 2 were submitted to one-lung ventilation, during 20 and 75 minutes respectively; groups 3 and 4 were submitted to two-lung ventilation during 20 and 75 minutes and considered controls. Ketamine/xylazine was administered for induction and maintenance of anesthesia. One-lung ventilation was achieved by administration of air into the interpleural space, and left lung collapse was visually confirmed through the centre of the diaphragm. Measurements: Lung histology preparations were observed under light microscopy for quantification of the inflammatory response (light, moderate and severe). Main results: All subjects had at least light inflammatory response. However, rabbits submitted to one-lung ventilation had a statistically significant value for the occurrence of moderate inflammation (p<0.05). The inflammatory response found included mainly eosinophils, with an average proportion of 75/25 to other polymorphonuclear cells. No differences between groups were found regarding gas exchange, heart rate and respiratory rate. Conclusions: In this spontaneous one-lung ventilation model, lung collapse was positively associated with a greater inflammatory response when compared to normal two-lung ventilation

A construção da auto-imagem do MST na sua mídia e suas relações estratégicas de inserção social global

This article analyzes the relationship between social movements and media. Its purpose is to identify how the media produced by the Landless Rural Workers’ Movement (Movimento dos Trabalhadores Sem Terra, MST), defines the self-image of their people, actions and social settings as opposed to the image of disqualification and criminalization predominantly presented by mainstream media.The empirical objects of the analyses consist of editions of the Movement’s newspaper O Jornal Sem Terra and the magazine Revista Sem Terra (from 2006 to 2007), it was also analyzed radio programs produced by the community radio 25 de Maio, in Madalena, Ceará State, during a week, in 2009, and the Movement’s website on the same year.Key words: social movements, Movement of Landless Rural Workers, media.O objetivo geral deste trabalho é aprofundar a análise das relações entre os movimentos sociais e a mídia, identificando como a mídia produzida pelo Movimento dos Trabalhadores Rurais sem Terra (MST), particularmente, produz a autoimagem qualificada de seus sujeitos, lutas e cenários sociais em contraposição à imagem de desqualificação e de criminalização predominantemente apresentada pela mídia convencional, como estratégia para a inserção social global do movimento. Esta análise será feita a partirda mídia produzida pelo MST: o “Jornal sem Terra” e a “Revista sem Terra”, cuja análise foi realizada no período de 2006 a 2007; aprogramação da rádio comunitária 25 de Maio (Madalena, Ceará), acompanhada durante uma semana em 2009; e o site do MST, analisado, também, em 2009.Palavras-chave: movimentos sociais, MST, mídia

ADHERENCE TO SELF-CARE IN PATIENTS WITH NEUROGENIC LOWER URINARY TRACT DYSFUNCTION: INSTRUMENT VALIDATION

Objective: To build and validate the content of the instrument for adherence to self-care for patients with Neurogenic Lower Urinary Tract Dysfunction who perform intermittent self-catheterization as to appearance and content.Method: Methodological study of instrument content validation, composed of three stages: literature review, instrument construction and instrument validation, respectively. The analysis was performed using the Agree model, and by calculating the content validation index, between 2020 and 2021. Results: Agree II, showed a result of 85.6% and 84.5% for validation of the scope and purpose and stakeholder domains. In content validation, the family history item was removed from the instrument with a content vanity index of 0.77.Conclusion: The instrument will contribute to offering subsidies for professional practice and to patients with the dysfunction

Treatment-resistant depression and major depression with suicide risk — the cost of illness and burden of disease

Introduction: Treatment-Resistant Depression (TRD) and Major Depression with Suicide Risk (MDSR) are types of depression with relevant effects on the health of the population and a potentially significant economic impact. This study estimates the burden of disease and the costs of illness attributed to Treatment-Resistant Depression and Major Depression with Suicide Risk in Portugal. Methods: The disease burden for adults was quantified in 2017 using the Disability-Adjusted Life Years (DALYs) lost. Direct costs related to the health care system and indirect costs were estimated for 2017, with indirect costs resulting from the reduction in productivity. Estimates were based on multiple sources of information, including the National Epidemiological Study on Mental Health, the Hospital Morbidity Database, data from the Portuguese National Statistics Institute on population and causes of death, official data on wages, statistics on the pharmaceutical market, and qualified opinions of experts. Results: The estimated prevalence of TRD, MDSR, and both types of depression combined was 79.4 thousand, 52.5 thousand, and 11.3 thousand patients, respectively. The disease burden (DALY) due to the disability generated by TRD alone, MDSR alone, and the joint prevalence was 25.2 thousand, 21 thousand, and 4.5 thousand, respectively, totaling 50.7 thousand DALYs. The disease burden due to premature death by suicide was 15.6 thousand DALYs. The estimated total disease burden was 66.3 thousand DALYs. In 2017, the annual direct costs with TRD and MDSR were estimated at € 30.8 million, with the most important components being medical appointments and medication. The estimated indirect costs were much higher than the direct costs. Adding work productivity losses due to reduced employment, absenteeism, presenteeism, and premature death, a total cost of € 1.1 billion was obtained. Conclusions: Although TRD and MDSR represent relatively small direct costs for the health system, they have a relevant disease burden and extremely substantial productivity costs for the Portuguese economy and society, making TRD and MDSR priority areas for achieving health gains.info:eu-repo/semantics/publishedVersio