15,607 research outputs found

    ‘TB OR NOT TB?’: A Importância de um Rastreio Adequado

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    Anaphylaxis to clavulanic acid: seven-year survey

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    Inhibition of Nuclear Factor of Activated T-Cells (NFAT) Suppresses Accelerated Atherosclerosis in Diabetic Mice

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    OBJECTIVE OF THE STUDY: Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: Streptozotocin (STZ)-induced diabetes in apolipoprotein E(-/-) mice resulted in 2.2 fold increased aortic atherosclerosis and enhanced pro-inflammatory burden, as evidenced by elevated blood monocytes, endothelial activation- and inflammatory markers in aorta, and pro-inflammatory cytokines in plasma. In vivo treatment with the NFAT blocker A-285222 for 4 weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, having no effect in non-diabetic mice. STZ-treated mice exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. NFAT-dependent transcriptional activity was examined in aorta, spleen, thymus, brain, heart, liver and kidney, but only augmented in the aorta of diabetic mice. A-285222 completely blocked this diabetes-driven NFAT activation, but had no impact on the other organs or on splenocyte proliferation or cytokine secretion, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. Instead, NFAT inhibition effectively reduced IL-6, osteopontin, monocyte chemotactic protein 1, intercellular adhesion molecule 1, CD68 and tissue factor expression in the arterial wall and lowered plasma IL-6 in diabetic mice. CONCLUSIONS: Targeting NFAT signaling may be a novel and attractive approach for the treatment of diabetic macrovascular complications

    Abordagem Clínica e Terapêutica de Doentes Internados por COVID-19: Uma Coorte Pediátrica em Portugal

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    Introduction: Coronavirus disease 2019, or COVID-19, in children is usually a mild disease, but severe illness has been reported. Currently, the therapy benefits of antiviral experimental drugs are still uncertain. The main aim of this study is to describe the experience of a level III hospital regarding therapeutic management of hospitalized children with COVID-19 and to characterize clinical features and evolution. Material and methods: This is a descriptive study of patients with COVID-19 in a level III pediatric hospital in Portugal between March and June 2020. Experimental drugs were administered according to the best scientific evidence at the time as 'off-label use'. Results: Among 200 children with SARS-CoV-2 infection, 37 were admitted due to COVID-19. Median age was one year (23 days - 18 years), 43% had comorbidities and 20/37 (54%) received antiviral therapy. Hydroxychloroquine was administered in 13 patients, in monotherapy or combined with lopinavir/ritonavir or azithromycin. Lopinavir/ritonavir was administered in eight patients and three children were treated with remdesivir. The patients who were treated had pneumonia (14), multisystem inflammatory syndrome in children (2), sepsis (2), myocarditis (1), acute respiratory distress syndrome (1), and mild illness with comorbidities (3). Other therapies included methylprednisolone and immunoglobulin (3), enoxaparin (2), antibiotics (16), oxygen (7), corticosteroids, and other inhaled therapy (16). Discussion: Several treatment approaches have been proposed for severe COVID-19, even though none of them had been proven effective or approved for small children. Currently, remdesivir is approved for children aged above 12 years-old. Although 54% of our patients were treated with antivirals, it is important to understand that the favorable clinical evolution could be related with the natural course of the disease. Conclusion: A significant proportion of our population presented severe and critical disease, was hospitalized and received treatment according to the most recent data, although most patients had mild disease. COVID-19 treatment in children is a clinical challenge and clinical trials are urgently needed.info:eu-repo/semantics/publishedVersio

    Diagnostic Challenge in a Sickle Cell Disease Patient with COVID-19

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    Acute chest syndrome is a life-threatening complication in sickle cell disease. Infections are frequently implied, and like other viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be a trigger. In addition, due to their inflammatory status, they may present a higher risk for severe coronavirus disease 2019 (COVID-19). Pneumonia and acute chest syndrome share clinical, laboratory, and radiological features and may overlap, which makes their differential diagnosis especially challenging. We describe a case of an adolescent with homozygous sickle cell disease that developed acute chest syndrome in the context of COVID-19. With it, we intend to bring awareness to the potential role of imaging in the differential diagnosis and in establishing the best approach for the patient. Chest computed tomography findings were suggestive of an alternative diagnosis to COVID-19 pneumonia and red cell transfusion, fluid management, analgesics, and antibiotics were administered with favorable outcome.info:eu-repo/semantics/publishedVersio
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