Omega-9 Oleic Acid, the Main Compound of Olive Oil, Mitigates Inflammation during Experimental Sepsis

The Mediterranean diet, rich in olive oil, is beneficial, reducing the risk of cardiovascular diseases and cancer. Olive oil is mostly composed of the monounsaturated fatty acid omega-9. We showed omega-9 protects septic mice modulating lipid metabolism. Sepsis is initiated by the host response to infection with organ damage, increased plasma free fatty acids, high levels of cortisol, massive cytokine production, leukocyte activation, and endothelial dysfunction. We aimed to analyze the effect of omega-9 supplementation on corticosteroid unbalance, inflammation, bacterial elimination, and peroxisome proliferator-activated receptor (PPAR) gamma expression, an omega-9 receptor and inflammatory modulator. We treated mice for 14 days with omega-9 and induced sepsis by cecal ligation and puncture (CLP). We measured systemic corticosterone levels, cytokine production, leukocyte and bacterial counts in the peritoneum, and the expression of PPAR gamma in both liver and adipose tissues during experimental sepsis. We further studied omega-9 effects on leukocyte rolling in mouse cremaster muscle-inflamed postcapillary venules and in the cerebral microcirculation of septic mice. Here, we demonstrate that omega-9 treatment is associated with increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the proinflammatory cytokines TNF-alpha and IL-1 beta in peritoneal lavage fluid of mice with sepsis. Omega-9 treatment also decreased systemic corticosterone levels. Neutrophil migration from circulation to the peritoneal cavity and leukocyte rolling on the endothelium were decreased by omega-9 treatment. Omega-9 also decreased bacterial load in the peritoneal lavage and restored liver and adipose tissue PPAR gamma expression in septic animals. Our data suggest a beneficial anti-inflammatory role of omega-9 in sepsis, mitigating leukocyte rolling and leukocyte influx, balancing cytokine production, and controlling bacterial growth possibly through a PPAR gamma expression-dependent mechanism. The significant reduction of inflammation detected after omega-9 enteral injection can further contribute to the already known beneficial properties facilitated by unsaturated fatty acid-enriched diets

A list of land plants of Parque Nacional do Caparaó, Brazil, highlights the presence of sampling gaps within this protected area

Brazilian protected areas are essential for plant conservation in the Atlantic Forest domain, one of the 36 global biodiversity hotspots. A major challenge for improving conservation actions is to know the plant richness, protected by these areas. Online databases offer an accessible way to build plant species lists and to provide relevant information about biodiversity. A list of land plants of “Parque Nacional do Caparaó” (PNC) was previously built using online databases and published on the website "Catálogo de Plantas das Unidades de Conservação do Brasil." Here, we provide and discuss additional information about plant species richness, endemism and conservation in the PNC that could not be included in the List. We documented 1,791 species of land plants as occurring in PNC, of which 63 are cited as threatened (CR, EN or VU) by the Brazilian National Red List, seven as data deficient (DD) and five as priorities for conservation. Fifity-one species were possible new ocurrences for ES and MG states

As particularidades clínicas da otite média: Clinical features of otitis media

A otite média é um processo inflamatório de evolução abrupta, acompanhado pelo quadro clínico típico de inflamação na orelha média, sendo sua incidência prevalente em crianças, culminando em leves repercussões clínicas, mas que deve ser adequadamente diagnosticada e tratada. Este evento clínico pode ser agudo, subagudo ou crônico com aparições típicas, evolução e manejo clínico diferenciados. O seguinte artigo é uma revisão narrativa de literatura que visa analisar a respeito das principais particularidades clínicas da Otite Média. Diante das informações coletadas, pode se elucidar que a otite média é o fator causal para implicações negativas e antibioticoterapia em crianças, logo é essencial medidas para diagnose precoce para evitar repercussões na saúde destes

Estudo da ativação e apoptose plaquetária na infecção malárica por Plasmodium vivax

Submitted by Gilvan Almeida ([email protected]) on 2016-10-11T17:34:19Z No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2017-02-13T12:42:19Z (GMT) No. of bitstreams: 2 isabel_moraes_ioc_dout_2016.pdf: 16473497 bytes, checksum: d590a1a4a24a1ba72db65076887e2d19 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2017-02-13T12:42:19Z (GMT). No. of bitstreams: 2 isabel_moraes_ioc_dout_2016.pdf: 16473497 bytes, checksum: d590a1a4a24a1ba72db65076887e2d19 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilIntrodução: O Plasmodium vivax é responsável por cerca de 85% das infecções por malária no Brasil. A malária vivax sempre foi considerada uma infecção benigna. No entanto, formas mais graves da doença, como anemia grave e plaquetopenia tem sido descritas. Além disso, as causas para a plaquetopenia ainda não foram totalmente esclarecidas. As plaquetas podem ativar e interagir com monócitos, principalmente pela ligação da P-selectina. O número de agregados plaqueta-monócito (PMA) é um marcador sensível para a detecção da ativação plaquetária. Plaquetas são células anucleadas que possuem uma via de apoptose funcional, e a proteína anti-apoptótica Bcl-xL, membro da família Bcl-2, é uma mediadora chave da sobrevida de plaquetas. A apoptose de plaquetas e a sua ligação com leucócitos contribuem para a redução da contagem de plaquetas. Heme e hemozoína (Hz) são liberadas na circulação durante a infecção e contribuem para a patogênese da malária. Na presente tese, nós estudamos a ativação e apoptose plaquetária durante a infecção por P. vivax e investigamos a resposta de plaquetas ao heme e à Hz. Material e métodos: Sangue foi coletado de pacientes com malária vivax que se apresentaram à Fundação de Medicina Tropical Dr. Heitor Vieira Dourado-Manaus e também de controles. A formação de PMA, expressão de P-selectina, de caspases e de Bcl-xL foram analisadas. Plasma foi utilizado para a quantificação de mediadores inflamatórios Plaquetas isoladas foram estudadas quanto ao seu transcriptoma. Plaquetas de voluntários sadios foram incubadas com plasma de pacientes com malária vivax e de controles sadios e analisadas para a ativação de caspase 9. Além disso, plaquetas de controles foram incubadas com heme e hemozoína sintética (sHz) e a ativação de caspases e a exposição de fosfatidilserina (PS) foram analisadas. Inibidores de calpaínas e proteassoma foram utilizados para se avaliar a participação destes componentes na degradação de Bcl-xL. Resultados: Pacientes com malária vivax apresentaram uma baixa contagem de plaquetas quando comparados com sujeitos controles. No entanto, pacientes apresentaram um aumento do volume plaquetário médio-VPM quando comparados com controles Pacientes infectados com P. vivax mostraram aumento no número de PMA e de P-selectina em relação aos controles. Pacientes com malária vivax apresentaram aumento nos níveis plasmáticos de IL-6, IL-10, IL-1\03B2, IFN-\03B3, MCP-1, RANTES, PF4 e hemopexina quando comparados com controles. Pacientes com plaquetopenia grave possuíam níveis de haptoglobina menores quando comparados com controles ou com pacientes com contagem de plaqueta maior do que 50.000/ uL. A análise do transcriptoma revelou 215 genes que tinham aumento de expressão, de pelo menos 2x, e 189 genes que tinham diminuição de expressão, de pelo menos metade, em plaquetas de pacientes com malária vivax. Plaquetas incubadas com plasma de pacientes com malária vivax apresentaram aumento de ativação da caspase 9. Plaquetas de pacientes infectados com P. vivax apresentaram aumento da ativação das caspases 3 e 9, no entanto, a expressão de Bcl-xL foi a mesma entre pacientes e controles. Heme e sHz induziram a ativação das caspases 3 e 9 e também exposição de PS em plaquetas de controles. Heme induziu a degradação de Bcl-xL através da ativação de calpaínas e não do proteassoma. Conclusão: A ativação e apoptose plaquetária podem ser contribuir para a plaquetopenia observada na infecção por P. vivax e o heme e a hemozoína liberados durante a infecção são dois possíveis agentes causadores dessa baixa no número de plaquetasIntroduction: Plasmodium vivax is responsible for about 85% of malaria infections in Brazil. Vivax malaria has always been considered a benign infection. However, severe forms of the disease, such as severe anemia and thrombocytopenia have been described. In addition, the causes for thrombocytopenia are not well elucidated. Platelets can activate and interact with monocytes, mainly through P-selectin binding. Numbers of platelet-monocyte aggregates (PMA) are a sensitive marker for the detection of platelet activation. Platelets are anucleated cells that possess a functional apoptosis pathway and the survival protein Bcl-xL, a member of the Bcl-2 family, is a key mediator of platelet survival. Platelet apoptosis and binding to leukocytes contribute for reduced circulating platelet count. Heme and hemozoin are malarial toxins that are released into the bloodstream during malaria infection. Here we studied platelet activation and apoptosis during P. vivax infection and investigated responses of platelets to heme and hemozoin. Material and methods: Blood was collected from vivax malaria patients presenting to the Tropical Medicine Foundation Dr. Heitor Vieira Dourado-Manaus and also from controls. PMA formation, P-selectin, caspases and Bcl-xL expression were analyzed. Plasma was used for the quantification of inflammatory mediators Isolated platelets had their transcriptome analyzed. Platelets from healthy volunteers were incubated with plasma from vivax patients and controls subjects and analyzed for caspase 9 activation. Also, platelets from controls were incubated with heme and synthetic hemozoin (sHz) and caspase activation, and phosphatidylserine (PS) exposure were analyzed. Calpains and proteassome inhibitors were used to evaluate the role of those two components in Bcl-xL degradation. Results: Vivax malaria patients had a lower platelet count when compared to control subjects. However, patients had an increase in the mean platelet volume-MPV when compared to controls. P. vivaxinfected patients had increased numbers of PMA and P-selectin when compared to controls. Vivax patients had increased levels of plasma IL-6, IL-10, IL-1\03B2, IFN-\03B3, MCP-1, RANTES, PF4 and hemopexin when compared to controls. Patients with severe thrombocytopenia had lower haptoglobin levels when compared to controls or to patients with platelet count higher than 50,000/ uL. The transcriptome analysis revealed 215 genes that had increased expression, of at least 2 fold, and 189 genes that had lower expression, of at least by half, in platelets from vivax patients. Platelets incubated with plasma from vivax patients had increased caspase 9 activation Platelets from vivax patients showed increased activation of caspases 3 and 9, however, the expression of Bcl-xL was the same between patients and controls. Heme and sHz induced caspases 3 and 9 activation and PS exposure in platelets from controls. Heme induced degradation of Bcl-xL through the activation of calpains and not proteasome. Conclusion: Platelet activation and apoptosis may contribute to the thrombocytopenia observed during P. vivax infection and both heme and hemozoin are two possible players in this low platelet coun

Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis

Submitted by sandra infurna ([email protected]) on 2016-06-19T21:56:40Z No. of bitstreams: 1 flora_oliveira_etal_IOC_2016.PDF: 1127513 bytes, checksum: 2b33c8a8ebdd6279e2e149aaedca5a3a (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-06-19T22:20:25Z (GMT) No. of bitstreams: 1 flora_oliveira_etal_IOC_2016.PDF: 1127513 bytes, checksum: 2b33c8a8ebdd6279e2e149aaedca5a3a (MD5)Made available in DSpace on 2016-06-19T22:20:25Z (GMT). No. of bitstreams: 1 flora_oliveira_etal_IOC_2016.PDF: 1127513 bytes, checksum: 2b33c8a8ebdd6279e2e149aaedca5a3a (MD5) Previous issue date: 2016Made available in DSpace on 2016-07-08T12:22:05Z (GMT). No. of bitstreams: 3 flora_oliveira_etal_IOC_2016.PDF.txt: 55221 bytes, checksum: 6263327453588b424db910e20fddf55b (MD5) flora_oliveira_etal_IOC_2016.PDF: 1127513 bytes, checksum: 2b33c8a8ebdd6279e2e149aaedca5a3a (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2016Fundação 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 Fluminense. Faculdade de Ciências Médicas. 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.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Medicina Interna. 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 Estácio de Sá. Programa de Produtividade Científica. Rio de Janeiro, RJ, Brasil .Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. Themain component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA).We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels inmice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMPactivated protein kinase (AMPK) expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals.We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production.We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high inmonounsaturated fatty acids (MUFA)

Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis

Sepsis is characterized by a life-threatening organ dysfunction caused by an unbalanced host response to microbe infection that can lead to death. Besides being currently the leading cause of death in intensive care units worldwide, sepsis can also induce long-term consequences among survivors, such as cognitive impairment. Statins (lipid-lowering drugs widely used to treat dyslipidemia) have been shown to possess pleiotropic anti-inflammatory and antimicrobial effects. These drugs act inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, the limiting step in cholesterol biosynthesis. In this work, we evaluated the therapeutic effects of simvastatin in an animal model of sepsis. In previous study from our group, statin pretreatment avoided cognitive damage and neuroinflammation in sepsis survivors. Herein, we focused on acute inflammation where sepsis was induced by cecal ligation and puncture (CLP), and the animals were treated with simvastatin (2 mg/kg) 6 h after surgery. We measured plasma biochemical markers of organ dysfunction, cell migration, cell activation, bacterial elimination, production of nitric oxide 24 h after CLP, survival rate for 7 days, and cognitive impairment 15 days after CLP. One single administration of simvastatin 6 h after CLP was able to prevent both liver and kidney dysfunction. In addition, this drug decreased cell accumulation in the peritoneum as well as the levels of TNF-α, MIF, IL-6, and IL-1β. Simvastatin diminished the number of bacterial colony forming units (CFU) and increased the production of nitric oxide production in the peritoneum. Simvastatin treatment increased survival for the first 24 h, but it did not alter survival rate at the end of 7 days. Our results showed that posttreatment with simvastatin hampered organ dysfunction, increased local production of nitric oxide, improved bacterial clearance, and modulated inflammation in a relevant model of sepsis

Na/K-ATPase assay in the intact mice lung subjected to perfusion

Made available in DSpace on 2015-05-27T13:39:50Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) adriana_silvaetal_IOC_2014.pdf: 350633 bytes, checksum: 5135d467f38c8b0fb3cbe9daca32f22b (MD5) Previous issue date: 2014Fundação 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.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Bio-Manguinhos. Departamento de Reativos para Diagnóstico. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Bio-Manguinhos. Departamento de Reativos para Diagnóstico. 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 Federal do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Among the characteristics of acute respiratory distress syndrome (ARDS) is edema formation and its resolution depends on pneumocyte Na/K-ATPase activity. Increased concentration of oleic acid (OA) in plasma induces lung injury by targeting Na/K-ATPase and, thus, interfering in sodium transport. FINDINGS: Presently, we adapted a radioactivity-free assay to detect Na/K-ATPase activity in perfused lung mice, comparing the inhibitory effect of ouabain and OA. We managed to perfuse only the lung, avoiding the systemic loss of rubidium. Rb+ incorporation into lung was measured by inductively coupled plasma optical emission spectrometry (ICP OES) technique, after lung tissue digestion. Na/K-ATPase activity was the difference between Rb+ incorporation with or without ouabain. Lung Na/K-ATPase was completely inhibited by perfusion with ouabain. However, OA caused a partial inhibition. CONCLUSIONS: In the present work the amount of incorporated Rb+ was greater than seen in our previous report, showing that the present technique is trustworthy. This new proposed assay may allow researchers to study the importance of Na/K-ATPase activity in lung pathophysiology

Oleic acid administration improves survival and ameliorates clinical score in septic mice.

<p>Animals were treated with oleic acid for 14 days. On the 15^th day, mice were subjected to CLP, and (A) 6 and (B) 24 hours after surgery, the clinical score was evaluated as described in the Materials and Methods. (C) The survival rate was assessed for 7 days after CLP. Control groups received saline. Each group consisted of 15 to 23 animals (clinical score at 6 hours: sham = 15 animals, sham + OA = 18 animals and CLP and CLP + OA = 23 animal; at 24 hours: sham and sham + OA = 18 animals, CLP = 18 animals, CLP + OA = 22 animals) in 3 independent experiments. For survival rates, 10 animals from each group were analyzed. This is a representative curve from 3 independent experiments. p < 0.05 * CLP vs sham, # CLP vs CLP plus oleic acid; log-rank test for mortality and one-way ANOVA followed by Newman-Keuls test for the clinical score.</p

Oleic acid increases the transcription of the CPT1A gene in septic mice.

<p>Swiss mice were treated for 14 days with oleic acid. On the 15^th day, mice were subjected to CLP. The liver was removed 24 hours after CLP. CPT1A mRNA was detected by RT-PCR. A representative gel of (A) CPT1A and of the (B) control GAPDH gene transcription. The loading control was GAPDH. (C)The bands were analyzed by densitometry and are represented as the CPT1A/GAPDH ratio. Values represent mean and SEM from 5–6 animals per group.</p

OA alters fatty acid metabolism and organ dysfunction and improves sepsis outcome.

<p>CPT1A –carnitine palmitoyltransferase 1A; PPAR–peroxisome proliferator-activated receptor, UCP2 –uncoupling protein 2; AMPK—5' AMP-activated protein kinase. OA activates AMPK, increases CPT1A and UCP2 and decreases fatty acid synthesis, resulting in an increase in oxidative processes. PPAR activation leads to an increase in the expression of CPT1A and UCP2; consequently, the fatty acid oxidation will be enhanced. Augmented fatty acid oxidation leads to a decrease in the NEFA plasma levels. Decreased NEFA and ROS levels would improve organ dysfunction and increase survival rate.</p