Parasite, Compartments, and Molecules: Trick versus Treatment on Chagas Disease

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic to Latin America, standing out as a socio-economic problem for low-income tropical populations. Such disease affects millions of people worldwide and emerges in nonendemic areas due to migration and climate changes. The current chemotherapy is restricted to two nitroderivatives (benznidazole and nifurtimox), which is unsatisfactory due to limited efficacy (particularly in chronic phase) and adverse side effects. T. cruzi life cycle is complex, including invertebrate and vertebrate hosts and three developmental forms (epimastigotes, trypomastigotes, and amastigotes). In this chapter, we will discuss promising cellular and molecular targets present in the vertebrate-dwelling forms of the parasite (trypomastigotes and amastigotes). Among the cellular targets, the mitochondrion is the most frequently studied; while among the molecular ones, we highlight squalene synthase, C14α-sterol demethylase, and cysteine proteases. In this scenario, proteomics becomes a valuable tool for the identification of other molecular targets, and some previously identified candidates will be also discussed. Multidisciplinary studies are needed to identify novel key molecules in T. cruzi in order to increase trypanocidal activity and reduce mammalian toxicity, ensuring the development of novel drugs for Chagas disease

Mulher e ficção: as personagens femininas em "Os anos"

A pesquisa apresentada neste artigo buscou identificar as características presentes nas personagens femininas do livro Os anos, da autora inglesa Virginia Woolf. A partir dessa identificação, é possível fazer uma melhor análise de seu enredo, contexto e até mesmo a inserção de Woolf na crítica feminista. Com a leitura de teóricas na área de autoria feminina e dos textos críticos de Virginia, como Um teto todo seu, Women and writing e Mulheres e ficção, foi feito um estudo sobre o papel da autora mulher na literatura, como a criação de personagens femininas por essas escritoras é capaz de mudar a visão dos estereótipos até então existentes. Após esta pesquisa crítica, seguiu-se a leitura do livro em questão, buscado as características esperadas nas personagens. O resultado foi mais satisfatório que o esperado, com uma profusão de personalidades, destinos e críticas embutidas a tais protagonistas.

DETC Induces Leishmania Parasite Killing in Human In Vitro and Murine In Vivo Models: A Promising Therapeutic Alternative in Leishmaniasis

Background: Chemotherapy remains the primary tool for treatment and control of human leishmaniasis. However, currently available drugs present serious problems regarding side-effects, variable efficacy, and cost. Affordable and less toxic drugs are urgently needed for leishmaniasis. Methodology/Principal Findings: We demonstrate, by microscopy and viability assays, that superoxide dismutase inhibitor diethyldithiocarbamate (DETC) dose-dependently induces parasite killing (p,0.001) and is able to ??????sterilize?????? Leishmania amazonensis infection at 2 mM in human macrophages in vitro. We also show that DETC-induced superoxide production (p,0.001) and parasite destruction (p,0.05) were reverted by the addition of the antioxidant N-acetylcysteine, indicating that DETC-induced killing occurs through oxidative damage. Furthermore, ultrastructural analysis by electron microscopy demonstrates a rapid and highly selective destruction of amastigotes in the phagosome upon DETC treatment, without any apparent damage to the host cell, including its mitochondria. In addition, DETC significantly induced parasite killing in Leishmania promastigotes in axenic culture. In murine macrophages infected with Leishmania braziliensis, DETC significantly induced in vitro superoxide production (p = 0.0049) and parasite killing (p = 0.0043). In vivo treatment with DETC in BALB/C mice infected with Leishmania braziliensis caused a significant decrease in lesion size (p,0.0001), paralleled by a 100-fold decrease (p = 0.0087) in parasite burden. Conclusions/Significance: Due to its strong leishmanicidal effect in human macrophages in vitro, its in vivo effectiveness in a murine model, and its previously demonstrated in vivo safety profile in HIV treatment, DETC treatment might be considered as a valuable therapeutic option in human leishmaniasis, including HIV/Leishmania co-infection

Síntese, caracterização e estudo da atividade inibitória de novas dialquilfosforilarilidrazonas sobre o crescimento de tripanossomatídeos

A new series of dialkylphosphorylhydrazones was synthesized through the condensation of aromatic aldehydes with different phosphorylhydrazines. All synthesized compounds were characterized by IR, ¹H-NMR, 13C-NMR and 31P-NMR spectroscopies. The in vitro investigation of the activity of these compounds against Leishmania amazonensis promastigotes and epimastigotes of T. cruzi, showed an efficient inhibition of proliferation, at non toxic concentrations to mammalian cells. The results have shown some derivatives as potential antiparasitic agents against trypanosomatids

The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance

Chagas disease (CD) affects at least 6 million people in 21 South American countries besides several thousand in other nations all over the world. It is estimated that at least 14,000 people die every year of CD. Since vaccines are not available, chemotherapy remains of pivotal relevance. About 30% of the treated patients cannot complete the therapy because of severe adverse reactions. Thus, the search for novel drugs is required. Here we tested the benznidazole (BZ) combination with the repositioned drug disulfiram (DSF) and its derivative diethyldithiocarbamate (DETC) upon Trypanosoma cruzi in vitro and in vivo. DETC-BZ combination was synergistic diminishing epimastigote proliferation and enhancing selective indexes up to over 10-fold. DETC was effective upon amastigotes of the BZ- partially resistant Y and the BZ-resistant Colombiana strains. The combination reduced proliferation even using low concentrations (e.g., 2.5 µM). Scanning electron microscopy revealed membrane discontinuities and cell body volume reduction. Transmission electron microscopy revealed remarkable enlargement of endoplasmic reticulum cisternae besides, dilated mitochondria with decreased electron density and disorganized kinetoplast DNA. At advanced stages, the cytoplasm vacuolation apparently impaired compartmentation. The fluorescent probe H2-DCFDA indicates the increased production of reactive oxygen species associated with enhanced lipid peroxidation in parasites incubated with DETC. The biochemical measurement indicates the downmodulation of thiol expression. DETC inhibited superoxide dismutase activity on parasites was more pronounced than in infected mice. In order to approach the DETC effects on intracellular infection, peritoneal macrophages were infected with Colombiana trypomastigotes. DETC addition diminished parasite numbers and the DETC-BZ combination was effective, despite the low concentrations used. In the murine infection, the combination significantly enhanced animal survival, decreasing parasitemia over BZ. Histopathology revealed that low doses of BZ-treated animals presented myocardial amastigote, not observed in combination-treated animals. The picrosirius collagen staining showed reduced myocardial fibrosis. Aminotransferase de aspartate, Aminotransferase de alanine, Creatine kinase, and urea plasma levels demonstrated that the combination was non-toxic. As DSF and DETC can reduce the toxicity of other drugs and resistance phenotypes, such a combination may be safe and effective

Leishmania-Host Interplay: The Everlasting Rivalry

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-10-05T16:50:10Z No. of bitstreams: 1 Martiny A Leishmania...2005.pdf: 406429 bytes, checksum: ae384bd22ba7b8b5d04f19ead195e092 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-10-05T17:02:35Z (GMT) No. of bitstreams: 1 Martiny A Leishmania...2005.pdf: 406429 bytes, checksum: ae384bd22ba7b8b5d04f19ead195e092 (MD5)Made available in DSpace on 2018-10-05T17:02:35Z (GMT). No. of bitstreams: 1 Martiny A Leishmania...2005.pdf: 406429 bytes, checksum: ae384bd22ba7b8b5d04f19ead195e092 (MD5) Previous issue date: 2005Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES - PROCAD) and Fundação Oswaldo Cruz (FIOCRUZ).Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilAbstract: Parasitic protozoa of the genus Leishmania infect mammalian mononuclear phagocytic cells causing a potentially fatal disease with a broad spectrum of clinical manifestations. The drugs of choice used in the leishmaniasis therapy are significantly toxic, expensive and faced with a growing frequency of refractory infections. Thus the search for new leishmanicidal compounds is urgently required. In order to perform a proper drug design and to understand the modes of action of such compounds it is necessary to elucidade the intrincate cellular and molecular events that orchestrate the parasite biology. To invade host cells Leishmania recruit different surface receptors that may assist engaging the microbicidal responses. Even before gaining the intracellular millieu these pathogens can deactivate and/or subvert the phagocyte signal transduction machinery rendering these cells permissive to infection. In the present review we attempted to approach some of the most relevant cellular and biochemical invasion strategies employed by Leishmania parasites

Role of Polyamines in Parasite Cell Architecture and Function

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-30T16:24:43Z No. of bitstreams: 1 Santos MAV Role of polyamine....pdf: 5363930 bytes, checksum: 4eb56499ef9056fa0a37582a44752a58 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-30T16:32:25Z (GMT) No. of bitstreams: 1 Santos MAV Role of polyamine....pdf: 5363930 bytes, checksum: 4eb56499ef9056fa0a37582a44752a58 (MD5)Made available in DSpace on 2018-05-30T16:32:25Z (GMT). No. of bitstreams: 1 Santos MAV Role of polyamine....pdf: 5363930 bytes, checksum: 4eb56499ef9056fa0a37582a44752a58 (MD5) Previous issue date: 2017FAPESB, PROEP/CNPq, PP-SUS and CAPES. MAVS is a CNPq research fellowFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose e outras Protozooses. Rio de Janeiro RJ, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose e outras Protozooses. Rio de Janeiro RJ, BrasilIn the absence of accessible, effective vaccines, the fight against parasitic disease relies mostly on chemotherapy. Nevertheless, the considerable side effects, high costs and growing number of refractory cases comprise substantial drawbacks. Thus, the search for new antiparasitic compounds remains a high priority. The polyamine biosynthesis, conversion and transport pathways offer different targets for selective chemotherapy. Polyamine analogues and other antagonists may provide tools in the search for new lead compounds. Light and electron microscopy techniques may encompass valuable approaches to elucidate the possible mechanisms of action of different antiparasitic compounds, allowing the identification of subcellular target compartments, presumably establishing the basis for a more rational drug design and/or planning of therapeutic strategies

Electron microscopy in antiparasitic chemotherapy: a (close) view to a kill

Submitted by Martha Martínez Silveira ([email protected]) on 2015-03-31T18:51:00Z No. of bitstreams: 1 Santos MAV Electron microscopy in antiparasitic chemotherapy.pdf: 989293 bytes, checksum: f3d2b41cdec7c503da0b5479c81f990f (MD5)Approved for entry into archive by Martha Martínez Silveira ([email protected]) on 2015-03-31T19:03:45Z (GMT) No. of bitstreams: 1 Santos MAV Electron microscopy in antiparasitic chemotherapy.pdf: 989293 bytes, checksum: f3d2b41cdec7c503da0b5479c81f990f (MD5)Made available in DSpace on 2015-03-31T19:03:45Z (GMT). No. of bitstreams: 1 Santos MAV Electron microscopy in antiparasitic chemotherapy.pdf: 989293 bytes, checksum: f3d2b41cdec7c503da0b5479c81f990f (MD5) Previous issue date: 2009Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Biomorfologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, BrasilElectron microscopy may be useful in chemotherapy studies at distinct levels, such as the identification of subcellular targets in the parasites and the elucidation of the ultimate drug mechanism of action, inferred by the alterations induced by antiparasitic compounds. In this review we present data obtained by electron microscopy approaches of different parasitic protozoa, such as Trypanosoma cruzi, Leishmania spp., Giardia lamblia and trichomonads, under the action of drugs, demonstrating that the cell architecture organization is only determined in detail at the ultrastructural level. The transmission electron microscopy may shed light (i.e. electrons) not only on the affected compartment, but also on the manner it is altered, which may indicate presumable target metabolic pathways as well as the actual toxic or lethal effects of a drug. Cytochemical and analytical techniques can provide valuable information on the composition of the altered cell compartment, permitting the bona fide identification of the drug target and a detailed understanding of the mechanism underneath its effect. Scanning electron microscopy permits the recognition of the drug-induced alterations on parasite surface and topography. Such observations may reveal cytokinetic dysfunctions or membrane lesions not detected by other approaches. In this context, electron microscopy techniques comprise valuable tools in chemotherapy studie

Enteroparasitosis in Public Schools in Bahia: Parasitology Learning

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-06-08T12:40:32Z No. of bitstreams: 1 Fontes AMS Enteroparasitoses...pdf: 573458 bytes, checksum: 1130750bfb57df7a7934f89923aff125 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-06-08T12:47:14Z (GMT) No. of bitstreams: 1 Fontes AMS Enteroparasitoses...pdf: 573458 bytes, checksum: 1130750bfb57df7a7934f89923aff125 (MD5)Made available in DSpace on 2018-06-08T12:47:14Z (GMT). No. of bitstreams: 1 Fontes AMS Enteroparasitoses...pdf: 573458 bytes, checksum: 1130750bfb57df7a7934f89923aff125 (MD5) Previous issue date: 2017CNPq, Capes, FAPESB, INCT and PRONEXFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilParasitic diseases hamper progress in underdeveloped nations, compromising child physical and cognitive development. In order to control intestinal parasites, the popularization of science may enable prophylactic measures. Questionnaires were used to assess the students’ knowledge, attitudes and practices. Health fairs were held as an educational tool and subsequently questionnaires on parasitic diseases and prevention were administered. Stool examinations were performed and infected students were treated. Prevalence of Entamoeba histolytica/ dispar, Ascaris lumbricoides, Trichuris trichiura was 7.1%, 5% and 3.5% respectively in the Anísio Teixeira Institute students and 7.2%, 8%, 3.6% in the Raymundo Matta School students in a suburb. The students at both schools displayed limited knowledge on parasitic disease prevention. The school participation in the prophylaxis of parasitic diseases, was not acknowledged by the students. Reviewing curricula is required, addressing themes related to health, possibly establishing partnerships with health services, universities and/or research centers with the effective involvement of the community performing articulated actions in different health districts, so that education will lead to community empowerment in regard to quotidian issues and improving public health conditions