Metabolic syndrome induces benefits in mice experiencing severe sepsis, comparable to the effects of low-dose aspirin pretreatment in septic mice lacking metabolic syndrome.

BACKGROUND: Sepsis is a complex condition characterized by systemic host inflammation caused by an infection. Experimental and observational studies indicate that obesity, one of the components of metabolic syndrome (MetS), or aspirin (ASA) treatment could be associated with sepsis survival. However, the effects of ASA on septic mice with MetS-induced conditions have not been explored. METHODS: Swiss mice were administered monosodium glutamate (MSG) (4 mg/kg) during their first 5 days of life for MetS induction, while the control mice received an equimolar saline solution. MetS was validated in male mice on their 60th day of life. ASA treatment was administered for 15 days prior to sepsis (40 mg/kg). On the 75th day, sepsis was induced in MetS and control mice through cecal ligation and puncture (CLP). The effects of ASA on septic mice with MSG-induced MetS were assessed by determining survival rates, quantification of nitric oxide (NO), and cytokine levels in the plasma, while correlating these data with hematological, blood glucose and cardiovascular parameters. RESULTS: MetS was validated by Lee-Index (3 body weight/naso-anal length×1000), hypertension, and hyperglycemia in animals receiving MSG as neonates. In control animals, severe sepsis promoted hypoglycemia, which was associated with mortality, as well as increased plasma NO levels, hypotension, hematological alterations, and elevation of proinflammatory cytokines. In contrast, MetS and pre-treatment with ASA were able to prevent sepsis-related alterations. CONCLUSIONS: MetS and ASA pre-treatment provided protection against severe sepsis. However, ASA was ineffective in mice with MetS undergoing severe sepsis.

Sera of Chagasic patients react with antigens from the tomato parasite Phytomonas serpens

The genus Phytomonas comprises trypanosomatids that can parasitize a broad range of plant species. These fagellates can cause diseases in some plant families with a wide geographic distribution, which can result in great economic losses. We have demonstrated previously that Phytomonas serpens 15T, a tomato trypanosomatid, shares antigens with Trypanosoma cruzi, the agent of human Chagas disease. Herein, two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were used to identify proteins of P. serpens 15T that are recognized by sera from patients with Chagas disease. After 2D-electrophoresis of whole-cell lysates, 31 peptides were selected and analyzed by tandem mass spectrometry. Twenty-eight polypeptides were identifed, resulting in 22 different putative proteins. The identifed proteins were classifed into 8 groups according to biological process, most of which were clustered into a cellular metabolic process category. These results generated a collection of proteins that can provide a starting point to obtain insights into antigenic cross reactivity among trypanosomatids and to explore P. serpens antigens as candidates for vaccine and immunologic diagnosis studies.

Regulação da linfoproliferação e da síntese de citocinas por prostaglandinas na infecção experimental por Trypanosoma cruzi / Regulation of lymphoproliferation and cytokines synthesis by prostaglandins in experimental Trypanosoma cruzi infection

A fase aguda da infecçao experimental pelo Trypanosoma cruzí caracteriza-se por apresentar supressao das respostas linfoproliferativas para mitógenos e antígenos do parasito. Este fenômeno tem sido explicado por vários mecanismos, incluindo a produçao exacerbada de óxido nítrico (NO) por macrófagos ativados e IL-2 insuficiente para sustentar o crescimento. Quando a supressao é máxima, o bloqueio da produçao de NO com NMLA (N _G_Monometil-L-arginina) nao restaura por completo a linfoproliferaçao ou aumenta a síntese de IL-2. Esses dados sugerem que outros mediadores contribuem para imunossupressao observada na infecçao pelo T. cruzi. Neste trabalho nós investigamos a regulaçao de prostaglandinas (PG), fator de necrose tumoral (TNF-a) e NO sobre a produçao de citocinas e respostas linfoproiiferativas de células de baço (SC), obtidas de camundongos infectados com 5 x 103 formas sanguícolas de T. cruzi (cepa Y). Foram estudadas as respostas proliferativas destas células para antígenos do parasito e à Concanavalina A (Con A), utilizando como parâmetros: proliferaçao (incorporaçao de 3 H-Timidina) e quantificaçao de PGE2, nitrito e das citocinas IFN-g, IL-2, IL-12, TNF-a, IL-10 e IL-4, presentes nos sobrenadantes de culturas tratadas ou nao com inibidores da COX (indometacina), da iNOs (NMLA) e anticorpo monoclonal anti-TNF-a. Altos níveis de PGE2 TNF-a e NO foram produzidos durante a infecçao. TNF-a estimulou a síntese de PGE2 e NO, enquanto ambos mediadores inibiram a síntese de TNF-a. O bloqueio da produçao de PG também reduziu a síntese de NO, indicando que PG estimula a produçao de NO. O tratamento com indometacina ou NMLA estimulou a linfoproliferaçao das células de baço obtidas de animais com 6 e 22 dias de infecçao; no dia 14, quando a supressao da proliferaçao e produçao de NO era máxima, a inibiçao combinada da produçao de NO e PG, restaurou as respostas proliferativas antígeno-específicas e para Con A. O bloqueio da produçao de PG ou NO aumentou a síntese de IL-2, IFN-g e TNF-a mas nao de IL-12 e IL4 pelas células de baço; enquanto que os níveis de IL-10 nao foram reduzidos. Foi analisado também o fenótipo das células que proliferam (blastos) em resposta à estimulaçao com T-Ag e tratadas com indometacina, NMLA ou indometacina + NMLA. Nossos resultados sugerem uma expansao maior de populaçoes blásticas no compartimento T CD4+, pela açao dos inibidores utilizados. Camundongos infectados e tratados com indometacina ...(au)