. Finally, daily treatment of infected mice with CP-105,696 was accompanied by a significantly higher level of blood parasitemia, but not lethality, than that seen in vehicle-treated animals. In conclusion, our results suggest a role for LTB 4 during experimental T. cruzi infection. Chemoattractant molecules such as LTB 4 not only may play a major role in leukocyte migration into sites of inflammation in vivo but also, in the event of an infection, may play a relevant role in the activation of recruited leukocytes to kill the invading microorganism in an NO-dependent manner.Chagas' disease is a protozoan infection caused by Trypanosoma cruzi and is an important public health problem in much of Latin America. The murine model of Chagas' disease has been used to understand the pathophysiological mechanisms underlying the disease and host protection. In this model, host resistance developed against parasites is dependent on the production of inflammatory cytokines, especially interleukin-12, which triggers the production of gamma interferon (IFN-␥) by NK or T cells, and tumor necrosis factor alpha (TNF-␣) (1, 5-7). These cytokines can in turn activate macrophages to produce nitric oxide (NO), the main effector molecule that controls intracellular parasite replication (5, 10, 15, 31). In macrophages, NO is generated from the guanidino nitrogen atom of L-arginine by an inducible NADPH-dependent enzyme called inducible NO synthase (iNOS) (19,22). More recently, it was shown that chemoattractant molecules which act on G protein-coupled serpentine receptors, such as chemokines and platelet-activating factor (PAF), may also participate in the cascade of events leading to NO production and parasite killing (2, 3). On the other hand, interleukin-10 and transforming growth factor ␤ appear to modulate negatively the production of NO and T. cruzi killing induced by proinflammatory cytokines (28,29).Leukotrienes are metabolites of arachidonic acid and have been shown to induce leukocyte activation and/or recruitment in several models of inflammation (9, 14). Leukotriene B 4 (LTB 4 ) acts via G protein-coupled receptors and is enzymatically produced through the 5-lipoxygenase pathway (8,33). A previous study demonstrated the ability of LTB 4 to induce the uptake and killing of T. cruzi by murine macrophages (32). However, the mechanisms underlying LTB 4 -induced killing and whether this was relevant in vivo were not evaluated. Here we investigated the ability of LTB 4 to induce the production of NO and whether NO mediated LTB 4 -induced parasite killing by peritoneal macrophages infected with T. cruzi in vitro. As the actions of LTB 4 may be partially dependent on the release of secondary mediators, such as PAF (13,16,18,24), we also evaluated whether LTB 4 -induced NO production and parasite killing were PAF dependent. Finally, we investigated whether endogenous production of LTB 4 played a relevant role in the infection of mice with T. cruzi in vivo.

The generation of an inflammatory response driven by Trypanosoma cruzi or its subproducts appears to be essential for tissue injury and disease pathogenesis. However, this inflammatory response is also relevant in the control of T. cruzi replication. The lipid mediator platelet-activating factor (PAF) has been implicated in a number of pathological conditions characterized by tissue inflammation. In the present study, we aimed at evaluating the role of PAF during T. cruzi infection by using mice that were genetically deficient in the PAF receptor. We observed that infected hearts of PAFR(-/-) mice had an increased number of parasite nests, associated with a more intense inflammatory infiltrate. This was associated with greater parasitemia and lethality. When wild-type and PAFR(-/-) mice were compared, there were no marked changes in the kinetics of the expression of MCP-1, RANTES, IFN-gamma and TNF-alpha in heart tissue of infected animals. Moreover, serum concentrations of TNF-alpha, nitrate and parasite-specific IgM were similar in both groups of mice. In vitro, macrophages from PAFR(-/-) animals did not phagocytose trypomastigote forms when activated with PAF, leukotriene B(4) or MCP-1 and produced less nitric oxide when infected and activated with IFN-gamma. These results are consistent with the hypothesis that endogenous synthesis of PAF and activation of PAF receptors control T. cruzi replication in mice in great part via facilitation of the uptake of the parasite and consequent activation of macrophages.

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Acupuncture is a therapy of the traditional Chinese medicine technique, which over the years has been widespread in the West. Defined as a needle-point treatment technique (acupoints), exactly preconfigured in the body to produce a specific physiological reaction to restore the balance between the function of conflicting states and homeostasis, alternating states of energy and thus maintain the ideal organ and body organization. Thus, the objective of this study was to map and describe the main points of acupuncture in the species Boa constrictor , and their indications to promote the balance of this species. The unprecedented result of the mapping was the discovery of specific acupoints with individual location indications without distribution in specific meridians and dispersedly distributed in the body.