The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom

Envenomation by snakes of the species Bothrops atrox induces local and systemic effects. Local effects include drastic tissue damage and a marked inflammatory response as a result of the synthesis and release of a variety of protein and lipid mediators. Toll-like receptor (TLR) signaling pathways can play an important role in this response, leading to synthesis of these inflammatory mediators. This study investigated the influence of TLR2 on the acute inflammatory response induced by Bothrops atrox venom. Wild-type C57BL/6 mice (WT) and TLR2 gene knockout mice (TLR2(-/-)) were injected with Bothrops atrox venom (BaV), and the following responses to the venom were assessed in peritoneal exudate: leukocyte accumulation; release of mediators, including CCL-2, IL-10, IL-1 beta, IL-6 and LTB4; protein expression of COX-1 and COX-2; and quantification of their products PGE(2) and TXA(2). After injection with BaV, the TLR2(-/-) mice (TLR2(Bav)(-/-)) had higher levels of IL-6 and CCL-2 than WT animals kept under the same conditions (WTBav), together with an accumulation of polymorphonuclear leukocytes (PMNs), inhibition of IL-1 beta and LTB4 and reduced mononuclear leukocyte influx. However, no significant differences in COX 2 protein expression or PGE(2), TXA(2) and IL-10 production between the TLR2(Bav)(-/-) and WTBav animals were observed. Together, these results indicate that the signaling pathway activated by TLR2 acts by modulating the induced inflammatory response to BaV through the direct action of venom-associated molecular patterns (VAMPs) or indirectly by forming damage-associated molecular patterns (DAMPs) and that this may have important therapeutic implications. (C) 2016 Elsevier Ltd. All rights reserved.

Effect of photobiomodulation on endothelial cell exposed to Bothrops jararaca venom

Bleeding is a common feature in envenoming caused by Bothrops snake venom due to extensive damage to capillaries and venules, producing alterations in capillary endothelial cell morphology. It has been demonstrated, in vivo, that photobiomodulation (PBM) decreases hemorrhage after venom inoculation; however, the mechanism is unknown. Thus, the objective was to investigate the effects of PBM on a murine endothelial cell line (tEnd) exposed to Bothrops jararaca venom (BjV). Cells were exposed to BjV and irradiated once with either 660-or 780-nm wavelength laser light at energy densities of 4 and 5 J/cm(2), respectively, and irradiation time of 10 s. Cell integrity was analyzed by crystal violet and cell viability/mitochondrial metabolism by MTT assay. The release of lactic dehydrogenase (LDH) was quantified as a measure of cell damage. In addition, cytokine IL1-beta levels were measured in the supernatant. PBM at 660 and 780 nm wavelength was able to increase cellular viability and decrease the release of LDH and the loss of cellular integrity. In addition, the concentration of pro-inflammatory cytokine IL1-beta was reduced after PBM by both wavelengths. The data reported herein indicates that irradiation with red or near-infrared laser resulted in protection on endothelial cells after exposure to Bothrops venom and could be, at least in part, a reasonable explanation by the beneficial effects of PBM inhibiting the local effects induced by Bothrops venoms, in vivo

Lemnitoxin, the major component of Micrurus lemniscatus coral snake venom, is a myotoxic and pro-inflammatory phospholipase A(2)

The venom of Micrurus lemniscatus, a coral snake of wide geographical distribution in South America, was fractionated by reverse-phase HPLC and the fractions screened for phospholipase A(2) (PLA(2)) activity. The major component of the venom, a PLA(2), here referred to as 'Lemnitoxin', was isolated and characterized biochemically and toxicologically. It induces myotoxicity upon intramuscular or intravenous injection into mice. The amino acid residues Arg15, Ala100, Asn108, and a hydrophobic residue at position 109, which are characteristic of myotoxic class I phospholipases A(2), are present in Lemnitoxin. This PLA(2) is antigenically related to M. nigrocinctus nigroxin, Notechis scutatus notexin, Pseudechis australis mulgotoxin, and Pseudonaja textilis textilotoxin, as demonstrated with monoclonal and polyclonal antibodies. Lemnitoxin is highly selective in its targeting of cells, being cytotoxic for differentiated myotubes in vitro and muscle fibers in vivo, but not for undifferentiated myoblasts or endothelial cells. Lemnitoxin is not lethal after intravenous injection at doses up to 2 mu g/g in mice, evidencing its lack of significant neurotoxicity. Lemnitoxin displays anticoagulant effect on human plasma and proinflammatory activity also, as it induces paw edema and mast cell degranulation. Thus, the results of this work demonstrate that Lemnitoxin is a potent myotoxic and proinflammatory class I PLA(2). (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Articulação entre Vigilância em Saúde e a Estratégia de Saúde da Família - debate

O Objetivo deste Ciclo de Debates foi promover uma ampla discussão sobre as questões teóricas e políticas que envolvem a Estratégia de Saúde da Família (ESF) no Rio de Janeiro. Arquivo disponível para audição e/ou download no ícone ao lado.

Articulação entre Vigilância em Saúde e a Estratégia de Saúde da Família - Carmen F. Teixeira

A pesquisadora traçou um panorama do cuidado em saúde fazendo uma revisão teórica sobre artigos, livros e registros históricos do sistema público de saúde. Apresentou pontos de vista conceituais e metodológicos de mais de cinco décadas e citou diferentes experiências utilizadas nos estados brasileiros. Pensávamos o cuidado de maneira mais horizontal, piramidal e, hoje, sabemos que devemos pensá-lo em uma perspectiva horizontalizada, distante daquela visão normativa de portas de entrada, difundida desde a década de 1960 pela Organização Pan-Americana de Saúde (Opas). Arquivos disponíveis para leitura, audição e/ou download nos ícones ao lado.