185 research outputs found
The role of corticosteroids in severe community-acquired pneumonia: a systematic review
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Previous issue date: 2008Instituto Nacional de Câncer. Unidade de Cuidados Intensivos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Hospital de São Francisco Xavier. Centro Hospitalar de Lisboa Ocidental. Unidade de Terapia Intensiva Médica. Lisboa, Portugal.Instituto Nacional de Câncer. Unidade de Cuidados Intensivos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Introduction: The purpose of this review was to evaluate the impact of corticosteroids on the outcomes of patients with severe community-acquired pneumonia (CAP). Methods: We performed a systematic MEDLINE, Cochrane database, and CINAHL search (1966 to November 2007) to
identify full-text publications that evaluated the use of corticosteroids in CAP. Results: An initial literature search yielded 109 articles, and 105
studies were excluded after the first analysis. We found four studies eligible for analysis. On the basis of their results, the use of corticosteroids as adjunctive therapy in severe CAP should be categorized as a weak recommendation (two studies) and a strong recommendation (two studies) with either low- or moderate-quality evidence. However, no evidence of adverse outcomes or harm is present in the evaluated studies. Conclusion: According to the GRADE system, available studies do not support the recommendation of corticosteroids as a standard of care for patients with severe CAP. Further randomized controlled trials with this aim should enroll a larger number of severely ill patients. However, in patients needing
corticosteroids, it may be reasonable to conclude that corticosteroid administration is safe in patients with severe infections receiving antimicrobial therapy
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
Toxoplasma gondii-skeletal muscle cells interaction increases lipid droplet biogenesis and positively modulates the production of IL-12, IFN-g and PGE2
Background: The interest in the mechanisms involved in Toxoplasma gondii lipid acquisition has steadily increased during the past few decades, but it remains not completely understood. Here, we investigated the biogenesis and the fate of lipid droplets (LD) of skeletal muscle cells (SkMC) during their interaction with T. gondii by confocal and electron microscopy. We also evaluated whether infected SkMC modulates the production of prostaglandin E2 (PGE2), cytokines interleukin-12 (IL-12) and interferon-gamma (INF-g), and also the cyclooxygenase-2 (COX-2) gene induction. Methods: Primary culture of skeletal muscle cells were infected with tachyzoites of T. gondii and analysed by confocal microscopy for observation of LD. Ultrastructural cytochemistry was also used for lipid and sarcoplasmatic reticulum (SR) detection. Dosage of cytokines (IL-12 and INF-g) by ELISA technique and enzyme-linked immunoassay (EIA) for PGE2 measurement were employed. The COX-2 gene expression analysis was performed by real time reverse transcriptase polymerase chain reaction (qRT-PCR). Results: We demonstrated that T. gondii infection of SkMC leads to increase in LD number and area in a time course dependent manner. Moreover, the ultrastructural analysis demonstrated that SR and LD are in direct contact with parasitophorous vacuole membrane (PVM), within the vacuolar matrix, around it and interacting directly with the membrane of parasite, indicating that LD are recruited and deliver their content inside the parasitophorous vacuole (PV) in T. gondii-infected SkMC. We also observed a positive modulation of the production of IL-12 and IFN-g, increase of COX-2 mRNA levels in the first hour of T. gondii-SkMC interaction and an increase of prostaglandin E2 (PGE2) synthesis from 6 h up to 48 h of infection. Conclusions: Taken together, the close association between SR and LD with PV could represent a source of lipids as well as other nutrients for the parasite survival, and together with the increased levels of IL-12, INF-g and inflammatory indicators PGE2 and COX-2 might contribute to the establishment and maintenance of chronic phase of the T. gondii infection in muscle cell
Mitochondrial DNA, anti-tuberculosis drugs-induced hepatotoxicity and Alzheimer's disease
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
Mechanisms of leukocyte lipid body formation and function in inflammation
An area of increasingly interest for the understanding of cell signaling are the spatio-temporal aspects of the different enzymes involved in lipid mediator generation (eicosanoid-forming enzymes, phospholipases and their regulatory kinases and phosphatases) and pools of lipid precursors. The compartmentalization of signaling components within discrete and dynamic sites in the cell is critical for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme activation and function. We hypothesized that lipid bodies - inducible non-membrane bound cytoplasmic lipid domains - function as specialized intracellular sites of compartmentalization of signaling with major roles in lipid mediator formation within leukocytes engaged in inflammatory process. Over the past years substantial progresses have been made demonstrating that all enzymes involved in eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites for eicosanoid generation. Here we will review our current knowledge on the mechanisms of formation and functions of lipid bodies pertinent to inflammation
Integrated NMR and MS Analysis of the Plasma Metabolome Reveals Major Changes in One-Carbon, Lipid, and Amino Acid Metabolism in Severe and Fatal Cases of COVID-19
Lutzomyia longipalpis Saliva Triggers Lipid Body Formation and Prostaglandin E2 Production in Murine Macrophages
After the injection of saliva into the host's skin by sand flies, a transient erythematous reaction is observed, which is related to an influx of inflammatory cells and the release of various molecules that actively facilitate the blood meal. It is important to understand the specific mechanisms by which sand fly saliva manipulates the host's inflammatory responses. Herein, we report that saliva from Lutzomyia (L.) longipalpis, a widespread Leishmania vector, induces early production of eicosanoids. Intense formation of intracellular organelles called lipid bodies (LBs) was noted within those cells that migrated to the site of saliva injection. In vitro and ex vivo, sand fly saliva was able to induce LB formation and PGE2 release by macrophages. Interestingly, PGE2 production induced by L. longipalpis saliva was dependent on intracellular mechanisms involving phosphorylation of signaling proteins such as PKC-α and ERK-1/2 and subsequent activation of cyclooxygenase-2. Thus, this study provides new insights into the pharmacological properties of sand fly saliva and opens new opportunities for intervening with the induction of the host's inflammatory pathways by L. longipalpis bites
Oleic acid inhibits lung Na/K-ATPase in mice and induces injury with lipid body formation in leukocytes and eicosanoid production
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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
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