ABSTRACT
Chagas' disease, caused by the protozoan Trypanosoma cruzi, represents a serious health problem in Latin America, and the available chemotherapy, which is based on 2 nitro-derivatives, is not satisfactory. In folk medicine, natural products including naphthoquinones have been employed for the treatment of different parasitic diseases. In the pursuit of alternative drugs for Chagas' disease, we investigated the mechanism of action of the triazolic naphthoquinone (TN; 2,2-dimethyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)-2,3-dihydronaphtho[1,2-b]furan-4,5-dione), which is the most active compound against T. cruzi trypomastigotes among a series of naphthofuranquinones. TN was active against the 3 parasite forms producing a dose-dependent inhibitory effect. In epimastigotes, TN induced reservosome disruption, flagellar blebbing, Golgi disorganization, the presence of cytosolic concentric membrane structures and abnormal multiflagellar parasites. The treatment also led to the appearance of well-developed endoplasmic reticulum profiles surrounding organelles that associated with an increase in monodansylcadaverine labelling, suggesting autophagy as part of the TN mechanism of action. Interestingly, no ultrastructural damage was detected in the mitochondria of naphthoquinone-treated epimastigotes. Flow cytometric analysis demonstrated an impairment of mitosis, an increase in ROS production and the maintenance of mitochondrial membrane potential. TN could be a good starting point in the investigation of a chemotherapeutic approach for the treatment of Chagas' disease.
Subject(s)
Naphthoquinones/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Autophagy/drug effects , Flow Cytometry , Inhibitory Concentration 50 , Macrophages, Peritoneal/drug effects , Mice , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Mitosis/drug effects , Organelles/drug effectsABSTRACT
This work approaches the contradictions that are present in the teaching of Psychiatric Nursing and Mental Health in four public universities in the state of Rio Grande do Sul, Brazil. It consists of a qualitative study based on a dialectic referential. The instruments used for the investigation were the programs of the courses of Psychiatric Nursing and Mental Health and interviews with fifteen teachers and fourteen students of the area. The central themes of the analysis were the conceptions and scenarios in which the teaching of Psychiatric Nursing and Mental Health takes place. It was observed that these courses focus predominantly the concepts of normality and pathology during the cycle of life and are influenced by the discourse of preventive psychiatry and by psychoanalysis. It was also noticed that the courses mentioned adopt a psychodynamic approach. The majority of the training in the area still takes place in big psychiatric hospitals and emphasizes psychopathologies and its psychosocial determinations which consolidate the hospice model.
