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Belo Horizonte, Brazil

Bozza F.A.,Brazilian National Institute of Technology | Bozza F.A.,DOr Institute for Research and Education IDOR | D'Avila J.C.,Brazilian National Institute of Technology | D'Avila J.C.,Laboratorio Of Imunofarmacologia | And 6 more authors.
Shock | Year: 2013

Sepsis is a major cause of mortality and morbidity in intensive care units. Acute and long-term brain dysfunctions have been demonstrated both in experimental models and septic patients. Sepsis-associated encephalopathy is an early and frequent manifestation but is underdiagnosed, because of the absence of specific biomarkers and of confounding factors such as sedatives used in the intensive care unit. Sepsis-associated encephalopathy may have acute and long-term consequences including development of autonomic dysfunction, delirium, and cognitive impairment. The mechanisms of sepsis-associated encephalopathy involve mitochondrial and vascular dysfunctions, oxidative stress, neurotransmission disturbances, inflammation, and cell death. Here we review specific evidence that links bioenergetics, mitochondrial dysfunction, and oxidative stress in the setting of brain dysfunctions associated to sepsis. Copyright © 2013 by the Shock Society.

Japiassu A.M.,Oswaldo Cruz Foundation | Japiassu A.M.,Intensive Care Unit | Japiassu A.M.,Federal University of Rio de Janeiro | Santiago A.P.S.A.,Federal University of Rio de Janeiro | And 7 more authors.
Critical Care Medicine | Year: 2011

OBJECTIVE: Increasing evidence points to the role of mitochondrial dysfunction in the pathogenesis of sepsis. Previous data indicate that mitochondrial function is affected in monocytes from septic patients, but the underlying mechanisms and the impact of these changes on the patients' outcome are unknown. We aimed to determine the mechanisms involved in mitochondrial dysfunction in peripheral blood mononuclear cells from patients with septic shock. DESIGN: A cohort of patients with septic shock to study peripheral blood mononuclear cell mitochondrial respiration by high-resolution respirometry analyses and to compare with cells from control subjects. SETTING: Three intensive care units and an academic research laboratory. SUBJECTS: Twenty patients with septic shock and a control group composed of 18 postoperative patients without sepsis or shock. INTERVENTIONS: Ex vivo measurements of mitochondrial oxygen consumption were carried out in digitonin-permeabilized peripheral blood mononuclear cells from 20 patients with septic shock taken during the first 48 hrs after intensive care unit admission as well as in peripheral blood mononuclear cells from control subjects. Clinical parameters such as hospital outcome and sepsis severity were also analyzed and the relationship between these parameters and the oxygen consumption pattern was investigated. MEASUREMENTS AND MAIN RESULTS: We observed a significant reduction in the respiration specifically associated with adenosine-5′-triphosphate synthesis (state 3) compared with the control group (5.60 vs. 9.89 nmol O2/min/10 cells, respectively, p <.01). Reduction of state 3 respiration in patients with septic shock was seen with increased prevalence of organ failure (r =-0.46, p =.005). Nonsurviving patients with septic shock presented significantly lower adenosine diphosphate-stimulated respiration when compared with the control group (4.56 vs. 10.27 nmol O2/min/10 cells, respectively; p =.004). Finally, the presence of the functional F1Fo adenosine-5'-triphosphate synthase complex (0.51 vs. 1.00 ng oligo/mL/10 cells, p =.02), but not the adenine nucleotide translocator, was significantly lower in patients with septic shock compared with control cells. CONCLUSION: Mitochondrial dysfunction is present in immune cells from patients with septic shock and is characterized as a reduced respiration associated to adenosine-5′-triphosphate synthesis. The molecular basis of this phenotype involve a reduction of F1Fo adenosine-5′-triphosphate synthase activity, which may contribute to the energetic failure found in sepsis. Copyright © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.

de Sousa P.A.M.,Federal University of Rio de Janeiro | Vaisman M.,Federal University of Rio de Janeiro | Carneiro J.R.I.,Federal University of Rio de Janeiro | Guimaraes L.,Federal University of Rio de Janeiro | And 5 more authors.
Arquivos Brasileiros de Endocrinologia e Metabologia | Year: 2013

Objectives: To evaluate the prevalence of goiter and nodular disease in patients with class III obesity, and to correlate results with serum leptin levels and insulin resistance (IR) parameters. Subjects and methods: A cross-sectional study was performed to assess thyroid ultrasound (US) patterns, HOMA-IR, serum leptin, and TSH levels in obese patients and controls. Results: Thyroid volume was positively correlated with body mass index (BMI) (r = 0.240, p = 0.039) and with HOMA-IR (r = 0.329; p < 0.01). Thyroid US patterns were similar between groups. However, when data from the male group was considered, greater thyroid volume was detected in the obese group compared with controls (10.8 vs. 8.5 cm3; p = 0.04). Also, nodules were more frequently detected (67% vs. 18%), as were nodules requiring FNAB (33.3% vs. 0%, p ≥ 0.05-0.09), in this group. Conclusion: Although IR did not correlate directly with the presence of nodules, the results support the hypothesis of a direct association between insulin resistance and thyroid volume. © ABE&M todos os direitos reservados.

Dos Santos R.A.N.,Laboratorio Of Imunofarmacologia | Dos Santos R.A.N.,Mato Grosso State University | Dos Santos R.A.N.,University of Cuiaba | Batista J.,University of Cuiaba | And 9 more authors.
Parasitology | Year: 2011

Leishmaniasis is one of the neglected diseases. High cost, systemic toxicity, and diminished efficacy due to development of resistance by the parasites has a negative impact on the current treatment options. Thus, the search for a new, effective and safer anti-leishmanial drug becomes of paramount importance. Compounds derived from natural products may be a better and cheaper source in this regard. This study evaluated the in vitro anti-leishmanial activity of Spiranthera odoratíssima (Rutaceae) fractions and isolated compounds, using promastigote and amastigote forms of different Leishmania species. J774 A.1 macrophage was used as the parasite host cell for the in vitro assays. Evaluations of cytoxicity, nitric oxide (NO), interleukin-10 and in silico analysis were carried out. In vitro experiments showed that the fruit hexanic fraction (Fhf) and its alkaloid skimmianine (Skm) have a significant (P<0.001) effect against L. braziliensis. This anti-L. braziliensis activity of Fhf and Skm was due to increased production of NO and attenuation of IL-10 production in the macrophages at concentrations ranging from 1.6 to 40.0 μg/ml. The in silico assay demonstrated significant interaction between Skm and amino acid residues of NOS2. Skm is thus a promising drug candidate for L. braziliensis due to its potent immunomodulatory activity. © 2011 Cambridge University Press.

Goncalves De Albuquerque C.F.,Laboratorio Of Imunofarmacologia | Burth P.,Federal University of Fluminense | Younes Ibrahim M.,State University of Rio de Janeiro | Garcia D.G.,Laboratorio Of Imunofarmacologia | And 3 more authors.
Mediators of Inflammation | Year: 2012

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, 24h 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. Copyright © 2012 Cassiano Felippe Gonalves de Albuquerque et al.

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