Enrofloxacina e toltrazuril reduzem a infecção por Toxoplasma gondii em células trofoblásticas humanas e em explantes de vilos placentários humanos de terceiro trimestre

The classical treatment for congenital toxoplasmosis is based on combination of sulfadiazine and pyrimethamine plus folinic acid. Due to teratogenic effects and bone marrow suppression caused by pyrimethamine, the establishment of new therapeutic targets is indispensable to minimize the undesirable effects and improve the control of the infection. Previous studies demonstrated that enrofloxacin and toltrazuril were able to control the infection triggered by Neospora caninum and Toxoplasma gondii. Therefore, the aim of this present study was evaluate the efficacy of enrofloxacin and toltrazuril in the control of T. gondii proliferation in human trophoblast cells (BeWo lineage) and in human villous explants from third trimester. BeWo cells and villous were treated with several concentrations of enrofloxacin, toltrazuril, sulfadiazine, pyrimethamine or association (sulfadiazine + pyrimethamine) in other to verify their viability by MTT or LDH assay, respectively. Next, BeWo cells were infected with T. gondii RH (2F1 clone) or ME49 strain, whereas villous were infected only with RH strain (2F1 clone), after, both cells and villous were treated or not with the same antibiotics and analyzed to T. gondii intracellular proliferation by beta-galactosidase assay (for RH strain) or blue toluidine staining (for ME49 strain). ELISA was performed in the supernatant to evaluate the cytokine profile. Enrofloxacin and toltrazuril did not change strongly the viability in cells and villous. Furthermore, the drugs decreased the parasite intracellular proliferation regardless T. gondii strain in BeWo cells and villous explants when compared to untreated and infected conditions. In BeWo cells infected by RH, enrofloxacin induced high levels of IL-6 low levels of MIF, while both cytokines were upregulated by enrofloxacin and toltrazuril in BeWo cells infected by ME49 strain. Additionally, in villous explantes, enrofloxacin induced high MIF production. Thus, enrofloxacin and toltrazuril were able to control the parasitism in BeWo cells and villous explants, and probably it occurs by modulation of immune response in these cells or tissues and direct action on parasite, but future experiments are necessary to verify this hypothesis.

A análise de Jean-Jacques Rousseau sobre o Projeto de Paz perpetua do abade de Saint-Pierre

The numerous political theories of the modern time were committed to thesocial-political and economic restructuring of the European States, but parallel to those conceptions emerged proposals of a broader range regarding the concern with the harmony among the States and their respective external safety, that is, they envisioned an International System among the European States. In that purpose, the Project of peace by the abbé de Saint-Pierre which glimpses perpetual peace in Europe under institutionalized conditions in order to legitimate a space that aims at facilitating a unified market among the member States. In this context, the sovereign role stands out, given the fact that he is the mediator between the interests of the State and the objectives proposed by the International System of States. However, according to Jean-Jacques Rousseau’s point of view it is evident that the thought of Saint-Pierre is impregnated by a naivety regarding the sovereigns’ government policy and, moreover, for believing that, mediated by a confederal assembly, the princes would voluntarily agree to be part of this project of perpetual peace. Nevertheless, Rousseau does not consider impossible the realization of this project, however, to achieve peace it is necessary force. Therefore, the comprehension of this debate was only possible guided, mainly, by the analyses of the primary works of such thinkers and the theoretical basis of the experts that is necessary, for instance, Evaldo Becker, Gelson Fonseca Jr., Luiz Felipe de Andrade e Silva Sahd, José Oscar de Almeida Marques, José Benedito de Almeida Jr. who enabled a broad comprehension of the purpose to which we dedicated ourselves in this research, allowing the understanding of thekey concepts elaborated by the Genevan philosopher and the themes that concern the relationship between States.