CBmeter- a new medical device for early screening of metabolic diseases

Type 2 diabetes mellitus (T2DM) is a highly prevalent disease worldwide which is asymptomatic in about 44% of patients being critical to search for new ways of early diagnosis. Recent studies have demonstrated that the etiology of this disease may be associated with alterations in the function of the carotid body (CB), a chemosensor organ located within the bifurcation of the carotid artery. In animal models of metabolic syndrome it was observed that the CBs are overactivated, underlying diseases such as obesity, hypertension and T2DM. This discovery provided a new paradigm in the neuroendocrinology field, suggesting that diagnostic function of the CBs has predictive value for the development of metabolic diseases. Despite this fact, it is not common in clinical practice to look at the CBs as organs associated with endocrine dysfunction and we believe this is probably due to the nonexistence of a user-friendly, portable medical device that diagnosis the function of the CBs.info:eu-repo/semantics/publishedVersio

Descodificar sinais de sensores de oxigénio para diagnosticar...diabetes

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Caracterização da função do monóxido de azoto e glutationo hepáticos na sensabilidade periférica à insulina

xi RESUMO A acção da insulina no músculo esquelético depende de um reflexo parassimpático hepático que conduz à libertação de uma substância hepática sensibilizadora da insulina, designada por HISS, responsável por cerca de 55% do efeito hipoglicemiante da insulina. A acção da HISS é finamente regulada pelo monóxido de azoto (NO) hepático e pelo estado prandial, aumentando no período pós-prandial imediato e diminuindo progressivamente com as horas de jejum. A secreção da HISS pode ser inibida cirúrgica ou farmacologicamente, quer por desnervação selectiva do plexo anterior hepático, quer por administração de atropina, quer por inibição do sintase do NO (NOS) hepático. O objectivo geral do trabalho apresentado nesta dissertação foi a caracterização da via de transdução de sinal que conduz à libertação da HISS. O modelo utilizado neste estudo foi o rato Wistar. A sensibilidade à insulina foi avaliada através do teste rápido de sensibilidade à insulina (RIST). A primeira hipótese de trabalho testada foi que a sequência de eventos que conduzem à secreção da HISS inicia-se com a activação do sistema parassimpático hepático seguida de activação do NOS hepático com subsequente produção de NO e activação do guanilato ciclase (GC). Observou-se que a administração de um dador de NO reverteu a resistência à insulina induzida, quer por inibição do NOS hepático, quer por antagonismo dos receptores muscarínicos com atropina. Em contraste, a resistência à insulina produzida por inibição do NOS hepático não foi revertida por administração intraportal de acetilcolina (ACh). Constatou-se que a inibição do GC hepático diminuiu a sensibilidade à insulina. Estes resultados sugerem que: a ACh libertada no fígado induz a síntese de NO hepático que conduz à libertação da HISS, que por sua vez é modulada pelo GC hepático. A libertação da HISS em resposta à insulina é regulada pelo estado prandial. Uma vez que os níveis hepáticos de glutationo (GSH) se encontram, tal como a HISS, diminuídos no estado de jejum e aumentados após a ingestão de uma refeição, testou-se a hipótese de que o GSH hepático está envolvido na secreção da HISS. Observou-se que a depleção do GSH hepático induziu resistência à insulina, comparável à obtida após inibição do NOS hepático. Estes resultados suportam a hipótese de que o GSH hepático desempenha um papel crítico na acção periférica da insulina. Considerando que, no estado de jejum, tanto os níveis de GSH hepático como os níveis de NO hepático são baixos, testou-se a hipótese de que a co-administração intraportal de um dador de GSH e de um dador de NO promove um aumento da sensibilidade à insulina no estado de jejum, devido ao restabelecimento do mecanismo da HISS. Observou-se que a administração sequencial de dadores de GSH e de NO no fígado provocou um aumento na sensibilidade à insulina, dependente da dose de dador de GSH administrada. Concluiu-se portanto que ambos, GSH e NO, são essenciais para que o mecanismo da HISS esteja completamente funcional. O GSH e o NO reagem para formar um S-nitrosotiol, o S-nitrosoglutationo (GSNO). Os resultados supra-mencionados conduziram à formulação da hipótese de que a secreção/acção da HISS depende da formação de GSNO. Observou-se que a administração intravenosa de S-nitrosotióis (RSNOs) aumentou a sensibilidade à insulina, em animais submetidos a um período de jejum, ao contrário da administração intraportal destes fármacos, o que RSNOs têm uma acção periférica, mas não hepática, na sensibilidade à insulina. Os resultados obtidos conduziram à reformulação da hipótese da HISS, sugerindo que a ingestão de uma refeição activa os nervos parassimpáticos hepáticos levando à libertação de ACh no fígado que, por sua vez activa o NOS. Simultaneamente, ocorre um aumento dos níveis de GSH hepático que reage com o NO hepático para formar um composto nitrosado, o GSNO. Este composto mimetiza a acção hipoglicemiante da HISS no músculo esquelético. SUMMARY Insulin action at the skeletal muscle depends on a hepatic parasympathetic reflex that promotes the release of a hepatic insulin sensitizing substance (HISS) from the liver, which contributes 55% to total insulin action. HISS action is modulated by hepatic nitric oxide (NO) and also by the prandial status so as to, in the immediate ostprandial state, HISS action is maximal, decreasing with the duration of fasting. HISS secretion may be inhibited by interruption of the hepatic parasympathetic reflex, achieved either by surgical denervation of the liver or by cholinergic blockade with atropine, or by prevention of hepatic NO release, using NO synthase (NOS) antagonists. The main objective of this work was to characterize the signal transduction pathways that lead to HISS secretion by the liver. Wistar rats were used and insulin sensitivity was evaluated using the rapid insulin sensitivity test (RIST). The first hypothesis tested was that the sequence of events that lead to HISS secretion starts with an increase in the hepatic parasympathetic tone, followed by the activation of hepatic NOS and subsequent triggering of guanylate cyclase (GC). We observed that insulin resistance produced either by muscarinic receptor antagonism with atropine or by hepatic NOS inhibition was reversed by the intraportal administration of an NO donor. In contrast, intraportal acetylcholine (ACh) did not restore insulin sensitivity after NOS inhibition. We also observed that GC inhibition lead to a decrease in insulin sensitivity.These results suggest that the release of ACh in the liver activates hepatic NO synthesis in order to allow HISS secretion, through a signaling pathway modulated by GC. HISS release in response to insulin is controlled by the prandial status. The second hypothesis tested was that glutathione (GSH) is involved in HISS secretion since the hepatic levels of GSH are, like HISS action, decreased in the fasted state and increased after ingestion of a meal. We observed that hepatic GSH depletion led to insulin resistance of the same magnitude of that observed after inhibition of hepatic NOS. These results support the hypothesis that hepatic GSH is crucial in peripheral insulin action. Since, in the fasted state, both hepatic GSH and NO levels are low, we tested the hypothesis that intraportal o-administration of a GSH donor and an NO donor enhances insulin sensitivity in fasted Wistar rats, by restoring HISS secretion. We observed that GSH and NO increased insulin sensitivity in a GSH dose-dependent manner. We concluded that HISS secretion requires elevated levels of both GSH and NO in the liver. GSH and NO react to form a S-nitrosothiol, S-nitrosoglutathione (GSNO). The last hypothesis tested in this work was that HISS secretion/ action depends on the formation of GSNO. We observed that intravenous administration of -nitrosothiols (RSNOs) increased insulin sensitivity in animals fasted for 24 h, in contrast with the intraportal administration of the drug. This result suggests that RSNOs enhanced insulin sensitivity through a peripheral, and not hepatic, mechanism. The results obtained led to a restructuring of the HISS hypothesis, suggesting that the ingestion of a meal triggers the hepatic parasympathetic nerves, leading to the release of Ach in the liver, which in turn activates NOS. Simultaneously, hepatic GSH levels increase and react with NO to form a nitrosated compound, GSNO. S-nitrosoglutathione mimics HISS hypoglycaemic action at the skeletal muscle

Nutrition education strategies to promote vegetable consumption in preschool children: The Veggies4myHeart project

Objective: To test the efficacy of three nutrition education strategies on the intake of different vegetables in preschool children. Design: This is an experimental study conducted in four Portuguese preschools. The intervention consisted of 20-min educational sessions, once a week, for 5 weeks, with one of the following randomised educational strategies: Portuguese Food Wheel Guide (control), digital game, storybook, storybook and reward (stickers). All groups had repeated exposure to vegetables in all sessions. A preand post-test were conducted to determine vegetable intake, and a 6-month follow-up was realised. Setting: Preschools of Leiria district, Portugal. Participants: A sample of 162 children aged 3 to 6 years. All eligible children attending the preschools were invited to participate. Results: All interventions tested were effective in increasing vegetable consumption both in the short and medium term, without statistically significant differences, compared to the control group. Stickers were more effective in the short term than in the medium term. Conclusions: The nutritional education strategies associated with repeated exposure tested in this study were effective in promoting vegetable consumption in preschool children. The use of stickers may be a valid strategy to promote the consumption of vegetables less recognised by children.info:eu-repo/semantics/publishedVersio

PROVA DE TOLERÂNCIA A UMA REFEIÇÃO MISTA COMO MÉTODO DE RASTREIO DE DIABETES GESTACIONAL: UMA REVISÃO NARRATIVA

The oral glucose tolerance test is, to this day, the gold standard method to screen for gestational diabetes mellitus, even though it can cause various side effects. To outcome this problem, a few studies have tested the use of a Mixed Meal Tolerance Test in pregnant women as an alternative to the glucose load, which are reviewed in this article. After analyzing these studies, it can be concluded that the Mixed Meal Tolerance Test could be a viable alternative to the gold standard, although further studies should be conducted.info:eu-repo/semantics/publishedVersio

Nutrition education strategies to promote vegetable consumption in preschool children - The Veggies4myHeart Project

Funding: We are very grateful to the principals, teachers, staff, and families of the preschools with which we partnered on this project. Financial support: This work was funded by ‘Challenges in Cardiology Accelerator Program 2018’and by Portuguese national funds provided by Fundação para a Ciência e Tecnologia (FCT) (UIDB/ 05704/2020 and UIDP/05704/2020).Objective: To test the efficacy of three nutrition education strategies on the intake of different vegetables in preschool children. Design: This is an experimental study conducted in four Portuguese preschools. The intervention consisted of 20-minutes educational sessions, once a week, for five weeks, with one of the following randomized educational strategies: Portuguese Food Wheel Guide (control), digital game, storybook, storybook and reward (stickers). All groups had repeated exposure to vegetables in all sessions. A pre- and post-test were conducted to determine vegetable intake and a 6-month follow-up was realized. Setting: Preschools of Leiria district, Portugal. Participants: A sample of 162 children aged 3 to 6 years. All eligible children attending the preschools were invited to participate. Results: All interventions tested were effective in increasing vegetable consumption both in the short and medium-term, without statistically significant differences, compared to the control group. Stickers were more effective in the short-term than in the medium term. Conclusions: The nutritional education strategies associated with repeated exposure tested in this study were effective in promoting vegetable consumption in preschool children. The use of stickers may be a valid strategy to promote the consumption of vegetables less recognized by children.publishersversionpublishe

Development of a mixed-meal that impacts carotid-body mediated cardiorespiratory and metabolic parameters - a pilot study

The carotid bodies (CB) have been recently implicated in the genesis of metabolic diseases in animal models. The CBs respond to circulating insulin to increase heart rate, respiratory rate and blood glucose levels. In humans, this mechanism is not well characterized.info:eu-repo/semantics/publishedVersio

Determinação da idade crítica para o aparecimento de obesidade infantil

A obesidade infantil constitui atualmente um grave problema de saúde pública. De acordo com a Organização Mundial de Saúde a obesidade infantil é um forte preditor de obesidade no adulto, incrementando o risco de desenvolvimento de doenças crónicas e representando um dos mais sérios desafios que a Europa terá de superar nos próximos anos. O estudo tem como objetivos: determinar a idade crítica para o aparecimento de excesso de peso e obesidade numa população de crianças dos 2 aos 10 anos de idade, avaliar fatores de risco para o aparecimento de obesidade na população em estudo hábitos tabágicos e ganho de peso da mãe durante a gravidez, diabetes gestacional, peso à nascença, ganho de peso durante os primeiros meses de vida, duração do aleitamento materno, número de horas de sono da criança, estatuto socioeconómico e IMC dos pais, hábitos alimentares e de atividade física da criança. Este estudo será realizado numa amostra de crianças dos 2 aos 10 anos de idade que frequentam instituições de ensino da região de Leiria. Os dados serão obtidos através de avaliações antropométricas e de um questionário aos pais. A análise estatística será realizada através do Programa SPSS e do Programa R. Será solicitado consentimento informado aos pais das crianças envolvidas no estudo. Perspetivam-se as implicações para a prática em saúde: Desenvolver estratégias de educação alimentar mais eficazes na idade considerada crítica para o desenvolvimento de obesidade.info:eu-repo/semantics/publishedVersio

Environment and health in children day care centers

This project addresses a set of common clinical problems in the context of children attending day care centres. It is common sense that children get sick more often as soon as they start attending a day care centre on a daily basis and this is particularly true for some groups at risk, as wheezing infants and wheezing pre-school childreninfo:eu-repo/semantics/publishedVersio

The NutriClock Study Protocol - Assessing the Impact of a Chrononutrition Intervention in Patients With Cardiometabolic Disturbances

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