Power to mechanical power to minimize ventilator-induced lung injury?

Mechanical ventilation is a life-supportive therapy, but can also promote damage to pulmonary structures, such as epithelial and endothelial cells and the extracellular matrix, in a process referred to as ventilator-induced lung injury (VILI). Recently, the degree of VILI has been related to the amount of energy transferred from the mechanical ventilator to the respiratory system within a given timeframe, the so-called mechanical power. During controlled mechanical ventilation, mechanical power is composed of parameters set by the clinician at the bedside-such as tidal volume (VT), airway pressure (Paw), inspiratory airflow (V'), respiratory rate (RR), and positive end-expiratory pressure (PEEP) level-plus several patient-dependent variables, such as peak, plateau, and driving pressures. Different mathematical equations are available to calculate mechanical power, from pressure-volume (PV) curves to more complex formulas which consider both dynamic (kinetic) and static (potential) components; simpler methods mainly consider the dynamic component. Experimental studies have reported that, even at low levels of mechanical power, increasing VT causes lung damage. Mechanical power should be normalized to the amount of ventilated pulmonary surface; the ratio of mechanical power to the alveolar area exposed to energy delivery is called "intensity." Recognizing that mechanical power may reflect a conjunction of parameters which may predispose to VILI is an important step toward optimizing mechanical ventilation in critically ill patients. However, further studies are needed to clarify how mechanical power should be taken into account when choosing ventilator settings

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Metabolic theory of pulmonary arterial hypertension: connecting mitochondrial roles with disease control

Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricular pressure overload and can lead to right-sided heart failure and death. A close link between PAH and cancer has been extensively suggested, with increasing evidence of a metabolic theory that underlies the pathogenesis of both diseases, mainly due to similarities in the processes responsible for triggering a hyperproliferative and apoptosis-resistant phenotype in both cardiopulmonary and malignant cells. Similar to cancer, abnormalities in mitochondrial biogenesis might lead to the following consequences: dysfunction of this organelle, which, in turn, causes the Warburg effect, a shift from mitochondrial respiration toward glycolysis, culminating in mitophagy in diseased pulmonary vessels and right ventricular cardiomyocytes. The role of these mitochondrial abnormalities offers new therapeutic avenues. Therefore, this study reviews the bases of mitochondrial derangements in PAH and explores the therapeutic implications of mitochondrial dysfunction and metabolic disturbances in cells from the pulmonary vasculature and right ventricular myocardium by addressing promising and challenging areas of investigation.La hipertensión arterial pulmonar (HAP) se caracteriza por una mayor resistencia vascular pulmonar, que provoca una sobrecarga de presión del ventrículo derecho (VD) y puede provocar insuficiencia cardíaca del lado derecho y la muerte. Se ha sugerido ampliamente un vínculo estrecho entre la HAP y el cáncer, con evidencia creciente de una teoría metabólica que subyace a la patogénesis de ambas enfermedades, principalmente debido a las similitudes en los procesos responsables de desencadenar un fenotipo hiperproliferativo y resistente a la apoptosis tanto en células cardiopulmonares como malignas. De manera similar al cáncer, las anomalías en la biogénesis mitocondrial pueden tener las siguientes consecuencias: Disfunción de este orgánulo, que a su vez provoca el efecto Warburg, un cambio de la respiración mitocondrial hacia la glucólisis, que culmina en una mitofagia en los vasos pulmonares enfermos y en los cardiomiocitos del ventrículo derecho. El papel de estas anomalías mitocondriales ofrece nuevas vías terapéuticas. Por lo tanto, este estudio revisa las bases de los trastornos mitocondriales en la HAP y explora las implicaciones terapéuticas de la disfunción mitocondrial y los trastornos metabólicos en las células de la vasculatura pulmonar y el miocardio del VD abordando áreas de investigación prometedoras y desafiantes.Sociedad Argentina de Fisiologí

New and personalized ventilatory strategies in patients with COVID-19

Coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus and may lead to severe respiratory failure and the need for mechanical ventilation (MV). At hospital admission, patients can present with severe hypoxemia and dyspnea requiring increasingly aggressive MV strategies according to the clinical severity: noninvasive respiratory support (NRS), MV, and the use of rescue strategies such as extracorporeal membrane oxygenation (ECMO). Among NRS strategies, new tools have been adopted for critically ill patients, with advantages and disadvantages that need to be further elucidated. Advances in the field of lung imaging have allowed better understanding of the disease, not only the pathophysiology of COVID-19 but also the consequences of ventilatory strategies. In cases of refractory hypoxemia, the use of ECMO has been advocated and knowledge on handling and how to personalize strategies have increased during the pandemic. The aims of the present review are to: (1) discuss the evidence on different devices and strategies under NRS; (2) discuss new and personalized management under MV based on the pathophysiology of COVID-19; and (3) contextualize the use of rescue strategies such as ECMO in critically ill patients with COVID-19

Impact of Bacillus Calmette–Guérin Moreau vaccine on lung remodeling in experimental asthma

AbstractWe analyzed the effects of different administration routes and application times of the BCG-Moreau strain on airway and lung inflammation and remodeling in a murine model of allergic asthma. BALB/c mice (n=168) were divided into two groups. The first group received BCG-Moreau strain while the second group received saline using the same protocol. BCG or saline were intradermally or intranasally injected one or two months before the induction of asthma. Mice were further sensitized and challenged with ovalbumin or received saline. Twenty-four hours after the last challenge, BCG prevented the triggering of pro-inflammatory cytokines, probably by increasing Foxp3 and interleukin (IL)-10, modulating eosinophil infiltration and collagen fiber deposition, thus reducing airway hyperresponsiveness. In conclusion, BCG-Moreau prevented lung remodeling in the present model of allergic asthma, regardless of administration route and time of vaccination. These beneficial effects may be related to the increase in regulatory T cells and to IL-10 production in tandem with decreased Th2 cytokines (IL-4, IL-5, and IL-13)

Evaluación isocinética de los músculos de la rodilla en jugadores de fútbol : análisis discriminante

Introdução: a atividade muscular em jogadores de futebol pode ser medida por meio do dinamômetro isocinético, que é um instrumento confiável para avaliação do desempenho humano. Objetivos: conduzir análises isocinéticas e discriminar quais variáveis diferenciam a categoria sub-17 (S17) da profissional (PRO).Métodos:Trinta e quatro jogadores de futebol (n=17 para cada categoria) foram avaliados. As variáveis isocinéticas utilizadas para a análise de extensão-flexão do joelho foram: pico de torque (Nm), trabalho total (J), potência média (W), ângulo de pico de torque (graus), razão agonista/antagonista (%), testadas em três velocidades (60°/s, 120°/s e 300°/s), com cada série contendo cinco repetições. Três análises discriminantes foram feitas usando o método Wilk's Lambda para identificar quais variáveis fariam uma discriminação significativa entre as duas categorias. Resultados: as variáveis discriminantes a 60°/s na categoria PRO foram: pico de torque extensores, trabalho total flexores, potência média de extensores e razão agonista/antagonista; e para os S17 foram: trabalho total de extensores, pico de torque de flexores e potência média de flexores. A 120°/s para a categoria PRO as variáveis discriminantes foram: pico de torque de flexores e potência média de extensores; para os S17 foram: trabalho total de extensores e potência média de flexores. A 300°/s, as variáveis encontradas para as categorias PRO e S17 foram, respectivamente: potência média de extensores e trabalho total de extensores. Conclusão: as variáveis isocinéticas para os músculos do joelho flexores e extensores foram capazes de fazer uma discriminação significativa entre jogadores de futebol PRO e S17.Introduction: muscle activity in soccer players can be measured by isokinetic dynamometer, which is a reliable tool for assessing human performance. Objectives: to perform isokinetic analyses and to determine which variables differentiate the under-17 (U17) soccer category from the professional (PRO). Methods: thirty four players were assessed (n=17 for each category). The isokinetic variables used for the knee extension-flexion analysis were: peak torque (Nm), total work (J), average power (W), angle of peak torque (deg.), agonist/ antagonist ratio (%), measured for three velocities (60°/s, 120°/s and 300°/s), with each series containing five repetitions. Three Wilks' Lambda discriminant analyses were performed, to identify which variables were more significant for the definition of each of the categories. Results: the discriminative variables at 60°/s in the PRO category were: extension peak torque, flexion total work, extension average power and agonist/antagonist ratio; and for the U17s were: extension total work, flexion peak torque and flexion average power. At 120°/s for the PRO category the discriminant variables were: flexion peak torque and extension average power; for the U17s they were: extension total work and flexion average power. Finally at 300°/s, the variables found in the PRO and U17 categories respectively were: extension average power and extension total work. Conclusion: isokinetic variables for flexion and extension knee muscles were able to significantly discriminate between PRO and U17 soccer players.Introducción: la actividad muscular en jugadores de fútbol puede ser medida por medio del dinamómetro isocinético, que es un instrumento confiable para evaluación del desempeño humano. Objetivos: conducir análisis isocinéticos y discriminar qué variables diferencian la categoría sub-17 (S17) de la profesional (PRO). Métodos: fueron evaluados treinta y cuatro jugadores de fútbol (n=17 para cada categoría). Las variables isocinéticas utilizadas para el análisis de extensión-flexión de la rodilla fueron: pico de torque (Nm), trabajo total (J), potencia media (W), ángulo de pico de torque (grados), razón agonista/antagonista (%), probadas en tres velocidades (60°/s, 120°/s y 300°/s), con cada serie conteniendo cinco repeticiones. Fueron realizados tres análisis discriminantes usando el método Wilk's Lambda para identificar qué variables harían una discriminación significativa entre las dos categorías. Resultados: las variables discriminantes a 60°/s en la categoría PRO fueron: pico de torque extensores, trabajo total flexores, potencia media de extensores y razón agonista/antagonista; y para los S17 fueron: trabajo total de extensores, pico de torque de flexores y potencia media de flexores. A 120°/s para la categoría PRO las variables discriminantes fueron: pico de torque de flexores y potencia media de extensores; para los S17 fueron: trabajo total de extensores y potencia media de flexores. A 300°/s, las variables encontradas para las categorías PRO y S17 fueron, respectivamente: potencia media de extensores y trabajo total de extensores. Conclusión: las variables isocinéticas para los músculos de la rodilla flexores y extensores fueron capaces de hacer una discriminación significativa entre jugadores de fútbol PRO y S17

Enzyme-assisted modification of flavonoids from Matricaria chamomilla: antioxidant activity and inhibitory effect on digestive enzymes

Matricaria chamomilla L. contains antioxidant flavonoids that can have their bioactivity enhanced by enzymatic hydrolysis of specific glycosyl groups. This study implements an untargeted metabolomics approach based on ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry technique operating in MSE mode (UPLC-QTOF-MSE) and spectrophotometric analysis of chamomile aqueous infusions, before and after hydrolysis by hesperidinase and ?-galactosidase. Several phenolic compounds were altered in the enzymatically treated infusion, with the majority being flavonoid derivatives of apigenin, esculetin, and quercetin. Although enzymatically modifying the infusion only led to a small increase in antioxidant activity (DPPH? method), its inhibitory effect on pancreatic lipase was of particular interest. The enzymatically treated infusion exhibited a greater inhibitory effect (EC50 of 35.6??M) than unmodified infusion and kinetic analysis suggested mixed inhibition of pancreatic lipase. These results are of great relevance due to the potential of enzymatically treated functional foods in human health3514249CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãosem informação2012/20393–

Demarcação da atividade anti-helmíntica do albendazol. Estudo referente à estrongiloidíase humana

A new antihelminthic agent, albendazole, was used in the treatment of 32 patients with strongyloidiasis. This trial included male and female adults, who were given 400 mg daily, as a single oral dose, for three days. The cure rates were assessed by stool examination performed according to the Rugai, Mattos and Brisola technique, with samples obtained seven, 14 and 21 days after the final dose of the drug. A mean cure rate of 28.1% was achieved, showing that though the drug was quite well tolerated by the recipients and that its role in the therapy of other intestinal helminthic infections had been established in previous investigations, its efficacy in the treatment of infections with Strongyloides stercoralis must be considered low.Os Autores utilizaram novo anti-helmíntico, o albendazol, no tratamento de 32 pessoas com estrongiloidíase. A casuística foi composta por adultos, de ambos os sexos, que receberam, pela via oral, dose cotidiana única de 400 mg, repetida em três oportunidades intervaladas por períodos de 24 horas. O controle da terapêutica sucedeu através de exames das fezes realizados sete, 14 e 21 dias após o término da administração, tendo sido empregado o método de Rugai, Mattos e Brisola. A porcentagem de curas verificada correspondeu a 28,1% e, ao lado da boa tolerância observada, essa constatação demonstrou baixa eficácia do medicamento em apreço no combate à infecção causada pelo Strongyloldes stercoralis, a despeito de méritos comprovados em investigações anteriores e concernentes a outras parasitoses intestinais

Utilização de substratos energéticos após exercício agudo de ratos treinados aerobiamente por natação

The aim of this study was to analyze the effect of aerobic training on utilization of energetic substrates of rats after a section of acute exercise. Wistar rats were distributed into two groups: control and trained. The training was accomplished in four weeks of swimming, 5 days/ week, 1 hour/day, with overload of 5% of body weight. After this, both groups were submitted to a section of 1 hour of exercise without overload. After sacrifice, blood samples were obtained to determine glucose, proteins and free fat acids (FFA) and liver and muscle samples to assess tissue glycogen. The training caused tendency to decrease in serum proteins after exercise and increase of serum glucose and muscular glycogen, but without statistic significance. Animals submitted to training presented increased values of liver glycogen and decreased of serum FFA. The results show that training alters the substrate mobilization pattern after acute exercise.O presente estudo objetivou analisar o efeito do treinamento aeróbio na utilização de substratos energéticos de ratos após sessão de exercício agudo. Ratos Wistar foram distribuídos nos grupos: controle e treinado. O treinamento consistiu em 4 semanas de natação, sendo 5 sessões semanais de 1 hora, com sobrecarga de 5% do peso corporal. Após esse período, os grupos foram submetidos à uma hora de natação sem carga e posteriormente sacrificados. Foram coletadas amostras sanguíneas para determinação de glicose, proteína, ácidos graxos livres (AGL) além de amostras do fígado e gastrocnêmico para análise do glicogênio. Observou-se que o treinamento não alterou as concentrações de proteína sérica, glicose sérica e glicogênio muscular após exercício agudo. Os animais submetidos ao treinamento apresentaram maiores valores de glicogênio hepático e menor concentração sérica de AGL. Conclui-se que o treinamento físico altera os padrões de mobilização de substratos após exercício agudo

Comparando abordagens terapêuticas no manejo da endometriose a partir de ensaios clínicos randomizados

A endometriose é uma condição ginecológica crônica que se caracteriza pela implantação ectópica de tecido funcional que reveste o útero, como glândulas e estroma endometrial, fora da cavidade uterina. A prevalência da endometriose gira em torno de 10% a 15% das mulheres em idade reprodutiva entre a população mundial, a qual aumenta para até 70% entre as mulheres que apresentam dor pélvica crônica. O presente estudo de revisão buscou avaliar novas abordagens terapêuticas para a endometriose, documentadas por meio de ensaios clínicos randomizados. Trata-se de uma pesquisa de revisão integrativa realizada por meio da base de dados PubMed, que levou em consideração os seguintes critérios de inclusão: testes controlados e randomizados; artigos publicados nos últimos 02 anos (2022-2024); que possuíam texto completo disponível e que abordassem acerca do manejo da endometriose. Ficou constatado que o pamoato de triptorrelina de liberação prolongada se mostrou uma opção terapêutica válida para o manejo da endometriose, com menos aplicações em comparação com o acetato de triptorrelina e com eficácia similar em relação à redução da dor. Além disso, verificou-se que o relugolix em terapia combinada se mostrou bem tolerado e com um perfil de segurança consistente, com baixa perda óssea, oferecendo uma opção adicional no tratamento da endometriose a longo prazo. Por fim, a terapia de coagulação híbrida com plasma de argônio (HybridAPC) foi considerado um tratamento cirúrgico promissor com impacto na prevenção de aderências, sendo um método seguro, rápido e que permite a preservação de tecidos no manejo da endometriose peritoneal