Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets

Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturatedfatty-acid-enriched diets

Oleic acid inhibits lung Na/K-ATPase in mice and induces injury with lipid body formation in leukocytes and eicosanoid production

Submitted by sandra infurna ([email protected]) on 2016-01-26T11:43:07Z No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2013.pdf: 2143360 bytes, checksum: 8f5e5674d7c469c0ea089e8c27de22ed (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-01-26T12:03:05Z (GMT) No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2013.pdf: 2143360 bytes, checksum: 8f5e5674d7c469c0ea089e8c27de22ed (MD5)Made available in DSpace on 2016-01-26T12:03:05Z (GMT). No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2013.pdf: 2143360 bytes, checksum: 8f5e5674d7c469c0ea089e8c27de22ed (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense.Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Mèdicas. Departamento de Medicina Interna. Rio de Janeiro, RJ, Brasil.Background: Acute respiratory distress syndrome (ARDS) can emerge from certain pathologies, such as sepsis, fat embolism and leptospirosis, in which the levels of unesterified fatty acids are increased in the patient’s plasma. ARDS is characterized by edema formation, and edema resolution occurs mainly due to the pneumocyte Na/K-ATPase activity. As previously described, increased oleic acid (OA) plasma concentrations induce lung injury by interfering with sodium transport. The first aim of this study was to develop a radioactivity-free assay to detect Na,K-ATPase activity ex vivo using a model of OA-induced lung injury in mice. We also investigated the relationship between Na/K-ATPase inhibition and OA-induced lung injury using ouabain-induced lung injury as a comparison, because of the well-described effect of ouabain as a Na/K-ATPase inhibitor. Methods: We developed a Na/K-ATPase assay based on the capture of non-radioactive Rb+ ions by mice lung tissue in the absence or presence of ouabain, a specific Na/K-ATPase inhibitor. Rb+ incorporation into the lung was measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) after lung tissue mineralization. Na/K-ATPase activity was considered as the difference between Rb+ incorporation in the absence and in the presence of ouabain. Bronchoalveolar lavage fluid was collected for lung injury assessment. For this assessment, cell counting, lipid body enumeration and lipid mediator concentrations were measured. Histological analyses were used to determinate lung pathology. Whole body plethysmographic analysis was performed to assay lung function. Results: The lung Na/K-ATPase activity of mice was completely inhibited by an OA dose of 10 μmol, an effect also obtained with 10-3 μmol of ouabain, as demonstrated by the decreased Rb+ incorporation in the lungs. The same OA dose induced lung edema and inflammation with cell influx, lipid body formation, and leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) production. Ouabain also induced lung inflammation, as detected by histological examinations. As far as we know, this is the first time that ouabain-induced lung injury was shown. Both OA and ouabain induced functional lung pathology in mice simultaneously with inhibition of the lung Na/K-ATPase activity. Conclusions: We developed a new non-radioactive assay to quantified Na/K-ATPase in vivo. OA and ouabain inhibited in vivo Na/K-ATPase activity in the lungs and induced lung injury. Our data reinforce the idea that Na/K-ATPase inhibitors may worsen lung injury in specific pathological conditions

Avaliação do perfil epidemiológico dos casos de síndrome respiratória aguda grave em residentes de Goiânia, entre 2013 e 2018

Objetivo: Analisar o perfil epidemiológico dos casos notificados de Síndrome Respiratória Aguda Grave em Goiânia. Métodos: Estudo de corte transversal dos casos notificados de Síndrome Respiratória Aguda Grave extraídos do Sistema de Informação de Agravos de Notificação Influenza Web, de 2013 a 2018, entre os residentes de Goiânia/GO. Realizou-se uma análise descritiva socioeconômica, com avaliação dos fatores associados por meio do teste qui-quadrado e análise multivariada por regressão logística. Resultados: Dos 1.379 casos notificados, 321 (23,30%) tinham de 0 a 5 anos e 236 (17,10%) mais que 60 anos, tendo estes uma chance de evoluir a óbito 4,01 maior que aqueles (p<0,001). Ao todo, 345 indivíduos (25,00%) vacinaram contra o vírus influenza, sendo que 106 (33,02%) tinham de 0 a 5 anos e 86 (36,44%), 60 anos ou mais. Em relação ao óbito, a presença de comorbidades (OR 1,87; IC95% 1,31; 2,65), internação em unidade de terapia intensiva (OR 7,66; IC95% 5,32; 11,04) e ausência de tratamento com antiviral (OR 5,93; IC95% 1,54; 22,85) foram fatores de risco associados. Apesar do vírus influenza A H1N1 ter sido o agente etiológico mais frequente, não foi observada relação entre tal vírus e óbito (p=0,397), assim como não foram identificados relação entre vacinação e internação em UTI, óbito e diminuição no tempo de internação dos pacientes. Conclusões: Indivíduos adultos e/ou que não vacinaram para gripe compõem o perfil das notificações. Aqueles que foram internados em unidade de terapia intensiva e portadores de comorbidade apresentaram maior chance de evoluir para óbito

Relationship between zingiberene, foliar trichomes and repellence of tomato plant to Tetranychus evansi

O objetivo deste trabalho foi quantificar os teores de zingibereno em populações segregantes (F2) do segundo retrocruzamento para Lycopersicon esculentum a partir da espécie selvagem L. hirsutum var. hirsutum, e verificar a relação entre estes teores e a densidade de tricomas glandulares e a repelência a Tetranychus evansi. Na quantificação do zingibereno, utilizou-se um método espectrofotométrico; os tricomas foram contados a partir de cortes paradérmicos e a resistência a ácaros foi avaliada por um bioteste de repelência. A seleção indireta quanto ao teor de zingibereno promoveu aumentos correlacionados no número de tricomas glandulares e na repelência ao ácaro, e o zingibereno nos tricomas glandulares participou efetivamente na resistência aos ácaros. A densidade de tricomas glandulares influencia de maneira determinante os teores de zingibereno, sendo que o tricoma tipo VI destacou-se por apresentar alta correlação com este aleloquímico. Os teores de zingibereno e a sua relação com tricomas glandulares e com a resistência a artrópodos-pragas se mantiveram ao longo dos retrocruzamentos, evidenciando a possibilidade de obtenção de plantas resistentes via seleção indireta para alto teor de zingibereno nos folíolos.The objective of this work was to quantify zingiberene contents in a segregating population (F2) of the second backcross generation to Lycopersicon esculentum after the initial cross with the wild species L. hirsutum var. hirsutum, and to analyse the relationship between zingiberene and both glandular trichome density on tomato leaves and levels of repellence to spider mites Tetranychus evansi. A spectrophotometric assay was used to quantify zingiberene in leaf disks. Trichome counting was made in paradermic preparations of leaf and mite repellence was accessed by a quick thumbtack assay. Indirect selection for high zingiberene contents increased both glandular trichome density and the level of mite repellence. Zingiberene in glandular trichomes therefore mediates mite repellence in the tomato population. Glandular trichome densities, especially that of type VI trichomes, were highly and positively correlated with zingiberene contents. High zingiberene levels and their relationship with both glandular trichome densities and resistance (repellence) to spider mites remained significant after two backcross generations, indicating an indirect selection for high zingiberene as an effective way of selecting mite resistant tomato genotypes

Exposure of cultured fibroblasts to the peptide PR-11 for the identification of induced proteome alterations and discovery of novel potential ligands.

The PR-11 peptide corresponds to the N-terminal and active region of the endogenously synthesized PR-39 molecule, of porcine origin. It is known to possess various biological effects including antimicrobial properties, angiogenic and anti-inflammatory activities. Apart from its reported activity as a proteasome inhibitor, a more comprehensive understanding of its function, at the molecular level, is still lacking. In this study, we used a label-free shotgun strategy to evaluate the proteomic alterations caused by exposure of cultured fibroblasts to the peptide PR-11. This approach revealed that more than half of the identified moleculeswere related to signalling, transcription and translation. Proteins directly associated to regulation of angiogenesis and interaction with the hypoxia-inducible factor 1-? (HIF-1?) were significantly altered. In addition, at least three differentially expressed molecules of the NF-?B pathway were detected, suggesting an anti-inflammatory property of PR-11. At last, we demonstrated novel potential ligands of PR-11, through its immobilization for affinity chromatography. Among the elutedmolecules, gC1qR, a known complement receptor, appearedmarkedly enriched. This provided preliminary evidence of a PR-11 ligand possibly involved in the internalization of this peptide. Altogether, our findings contributed to a better understanding of the cellular pathways affected by PR-39 derived molecules

Recommendations of Neuroendocrinology Department from Brazilian Society of Endocrinology and Metabolism for diagnosis and treatment of acromegaly in Brazil

A acromegalia é uma doença associada à elevada morbidade e à redução da expectativa de vida. Em virtude do seu caráter insidioso e do seu não reconhecimento, o diagnóstico é frequentemente realizado com atraso, o que, associado às complicações relacionadas ao excesso do GH/IGF-I, determina elevada morbimortalidade. No entanto, um diagnóstico precoce e um tratamento efetivo minimizam a morbidade e normalizam a taxa de mortalidade. Nesta publicação, o objetivo do Departamento de Neuroendocrinologia da Sociedade Brasileira de Endocrinologia e Metabologia é divulgar quando suspeitar clinicamente da acromegalia e como diagnosticá-la. Além disso, discute-se a maneira mais eficaz e segura de realizar o tratamento da acromegalia, enfatizando que este deve ser realizado em centros de referência. Assim, com base em dados publicados em periódicos de nível científico reconhecido e na experiência dos autores, são apresentadas as recomendações para o diagnóstico e tratamento da doença.Acromegaly is a disease associated with increased morbidity and reduced life expectancy. Because of its insidious character and its non-recognition, the diagnosis is often made with delay, which, along with the complications related to GH/IGF-I excess, determines high morbidity and mortality. However, an early diagnosis and an effective treatment reduce the morbidity and normalize the mortality rate. In this publication, the goal of Neuroendocrinology Department from Brazilian Society of Endocrinology and Metabolism is to disclose which clinical set should arouse the suspicious of acromegaly and how to diagnose it. Furthermore, we discuss the most effective and safe approach to perform the treatment of acromegaly, emphasizing that it must be carried out in reference centers. Therefore, based on data published in journals with recognized scientific level and authors' experience, recommendations are presented for diagnosis and treatment of the disease