Ru(II)/amino acid complexes inhibit the progression of breast cancer cells through multiple mechanism-induced apoptosis.

For some cancer subtypes, such as triple-negative breast cancer, there are no specific therapies, which leads to a poor prognosis associated with invasion and metastases. Ruthenium complexes have been developed to act in all steps of tumor growth and its progression. In this study, we investigated the effects of Ruthenium (II) complexes coupled to the amino acids methionine (RuMet) and tryptophan (RuTrp) on the induction of cell death, clonogenic survival ability, inhibition of angiogenesis, and migration of MDA-MB-231 cells (human triple-negative breast cancer). The study also demonstrated that the RuMet and RuTrp complexes induce cell cycle blockage and apoptosis of MDA-MB-231 cells, as evidenced by an increase in the number of Annexin V-positive cells, p53 phosphorylation, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Moreover, morphological changes and loss of mitochondrial membrane potential were detected. The RuMet and RuTrp complexes induced DNA damage probably due to reactive oxygen species production related to mitochondrial membrane depolarization. Therefore, the RuMet and RuTrp complexes acted directly on breast tumor cells, leading to cell death and inhibiting their metastatic potential; this reveals the potential therapeutic action of these drugs.

American trypanosomiasis and Chagas disease: Sexual transmission.

OBJECTIVE: To contribute to the discussion on the research findings indicating the sexual transmission of American trypanosomiasis and Chagas disease in humans. METHODS: A review of the literature was performed to investigate the routes of transmission of Trypanosoma cruzi parasites and to evaluate the distribution of Chagas disease, which is now found across five continents. RESULTS: The epidemiological profile of American trypanosomiasis, which is still considered a neglected disease of the poor people of Latin America, has changed over time. A family-based study demonstrated that the blood protozoan T. cruzi can be transmitted sexually from infected males and females to naïve mates. CONCLUSIONS: Evidence that Chagas disease can be transmitted sexually, coupled with the migration of individuals with Chagas disease to previously non-endemic countries and increased travel to endemic countries, has implications for public health. Improved screening of blood supplies and prenatal care are required to prevent congenital spread.

Febre Chikungunya um desafio para o sistema de vigilância sanitária em saúde: revisão sistemática / Chikungunya Fever, a challenge for the health surveillance system: a systematic review

Introdução: No cenário internacional, o vírus Chikungunya é importante causa de morbidade. Por dispersar-se rapidamente para locais em que são encontrados os mosquitos Aedes aegypti e Aedes albopictus, tornou-se um desafio para a vigilância em saúde mundial. Objetivos: Revisar a literatura científica sobre a ocorrência da Febre do Chikungunya e a resposta da vigilância em saúde frente a surtos e epidemias. Métodos: Revisão sistemática de estudos primários publicados no período de 2005 a 2015, pesquisados nas bases de dados MEDLINE, SCOPUS, Web of Science, TripDatabase e BVS, com estratégia de busca que utilizou descritores em saúde referentes ao vírus Chikungunya e à vigilância em saúde. Resultados: Foram selecionados 13 artigos sobre o tema proposto. Conclusão: Evidenciou-se a necessidade de potencializar a integração das redes de vigilância, instituições de saúde, laboratórios de diagnóstico e ações de combate ao vetor, para acelerar a detecção de casos importados e de transmissão autóctone, bem como eliminação do vetor competente

Introduction: The Chikungunya virus is an important cause of morbidity in the international scene. It rapidly disperses to the sites where the Aedes aegypti and Aedes albopictus mosquitoes are found. Because this, it is a challenge for global health surveillance. Objectives: To review the scientific literature about Chikungunya fever's incidence and the health surveillance response to outbreaks and epidemics. Methods: Systematic review of primary studies published between 2005 and 2015, searched in databases (MEDLINE, SCOPUS, Web of Science, TripDatabase and BVS) using a strategy with Medical Subject Headings about Chikungunya virus and health Surveillance. Results: Were found 13 articles about the proposed theme of study. Conclusion: It is necessary to strengthen the integration of surveillance networks, health institutions, diagnostic laboratories and anti-vector actions in order to facilitate the early detection of imported cases and autochthonous transmission, and the elimination of the vector

Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation.

BACKGROUND: Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. METHODS/PRINCIPAL FINDINGS: To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8ß+ effector cells that expressed TCRγδ, vß1 and vß2 receptors, which infiltrated the adult hearts and the reporter heart grafts. CONCLUSIONS/SIGNIFICANCE: Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease.

Trypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence of parasitism.

BACKGROUND: The administration of anti-trypanosome nitroderivatives curtails Trypanosoma cruzi infection in Chagas disease patients, but does not prevent destructive lesions in the heart. This observation suggests that an effective treatment for the disease requires understanding its pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: To understand the origin of clinical manifestations of the heart disease we used a chicken model system in which infection can be initiated in the egg, but parasite persistence is precluded. T. cruzi inoculation into the air chamber of embryonated chicken eggs generated chicks that retained only the parasite mitochondrial kinetoplast DNA minicircle in their genome after eight days of gestation. Crossbreeding showed that minicircles were transferred vertically via the germ line to chicken progeny. Minicircle integration in coding regions was shown by targeted-primer thermal asymmetric interlaced PCR, and detected by direct genomic analysis. The kDNA-mutated chickens died with arrhythmias, shortness of breath, cyanosis and heart failure. These chickens with cardiomyopathy had rupture of the dystrophin and other genes that regulate cell growth and differentiation. Tissue pathology revealed inflammatory dilated cardiomegaly whereby immune system mononuclear cells lyse parasite-free target heart fibers. The heart cell destruction implicated a thymus-dependent, autoimmune; self-tissue rejection carried out by CD45(+), CD8γδ(+), and CD8α lymphocytes. CONCLUSIONS/SIGNIFICANCE: These results suggest that genetic alterations resulting from kDNA integration in the host genome lead to autoimmune-mediated destruction of heart tissue in the absence of T. cruzi parasites.

Environment, interactions between Trypanosoma cruzi and its host, and health.

An epidemiological chain involving Trypanosoma cruzi is discussed at the environmental level, and in terms of fine molecular interactions in invertebrate and vertebrate hosts dwelling in different ecosystems. This protozoan has a complex, genetically controlled plasticity, which confers adaptation to approximately 40 blood-sucking triatomine species and to over 1,000 mammalian species, fulfilling diverse metabolic requirements in its complex life-cycle. The Tr. cruzi infections are deeply embedded in countless ecotypes, where they are difficult to defeat using the control methods that are currently available. Many more field and laboratory studies are required to obtain data and information that may be used for the control and prevention of Tr. cruzi infections and their various disease manifestations. Emphasis should be placed on those sensitive interactions at cellular and environmental levels that could become selected targets for disease prevention. In the short term, new technologies for social mobilization should be used by people and organizations working for justice and equality through health information and promotion. A mass media directed program could deliver education, information and communication to protect the inhabitants at risk of contracting Tr. cruzi infections.

Environment, interactions between Trypanosoma cruzi and its host, and health: [review] / Meio-ambiente, interações entre Trypanosoma cruzi e seu hospedeiro e saúde humana: [revisão]

An epidemiological chain involving Trypanosoma cruzi is discussed at the environmental level, and in terms of fine molecular interactions in invertebrate and vertebrate hosts dwelling in different ecosystems. This protozoan has a complex, genetically controlled plasticity, which confers adaptation to approximately 40 blood-sucking triatomine species and to over 1,000 mammalian species, fulfilling diverse metabolic requirements in its complex life-cycle. The Tr. cruzi infections are deeply embedded in countless ecotypes, where they are difficult to defeat using the control methods that are currently available. Many more field and laboratory studies are required to obtain data and information that may be used for the control and prevention of Tr. cruzi infections and their various disease manifestations. Emphasis should be placed on those sensitive interactions at cellular and environmental levels that could become selected targets for disease prevention. In the short term, new technologies for social mobilization should be used by people and organizations working for justice and equality through health information and promotion. A mass media directed program could deliver education, information and communication to protect the inhabitants at risk of contracting Tr. cruzi infections.

Uma rede epidemiológica envolvendo o Trypanosoma cruzi foi discutida nos níveis ambientais e de interações moleculares nos hospedeiros que habitam em 19 diferentes ecossistemas. O protozoário tem uma enorme plasticidade controlada geneticamente que confere sua adaptação a cerca de quarenta espécies de triatomíneos e mais de mil espécies de mamíferos. Essas infecções estão profundamente embutidas em inúmeros ecótopos, onde elas estão inacessíveis aos métodos de controle utilizados. Muito mais estudos de campo e de laboratório são necessários à obtenção de dados e informação pertinentes ao controle e prevenção das infecções pelo Tr. cruzi e as várias manifestações da doença. Ênfase deve ser dada àquelas interações que ocorrem nos níveis celulares e ambientais que se poderiam tomar como alvos seletivos para prevenção da doença. Novas tecnologias para mobilização social devem ser disponibilizadas para os que trabalham pela justiça e pela igualdade, mediante informação para a promoção da saúde. Um programa direcionado de educação de massa pode prover informação e comunicação necessárias para proteger os habitantes atualmente expostos ao risco de contrair as infecções pelo Tr. cruzi.

Heritable integration of kDNA minicircle sequences from Trypanosoma cruzi into the avian genome: insights into human Chagas disease.

We demonstrate the genetic transfer of DNA between eukaryotes from different kingdoms. The mitochondrial kinetoplast DNA (kDNA) of the intracellular parasite Trypanosoma cruzi is transferred to human patients with Chagas disease. This transfer was reproduced experimentally in rabbits and chickens. The kDNA is integrated into the host genome. In the human chromosomes, five loci were identified as integration sites, and the beta-globin locus and LINE-1 retrotransposons were frequently targeted. Short repeated sequences in the parasite and the target host DNAs favor kDNA integration by homologous recombination. Introduced kDNA was present in offspring of chronically infected rabbits and in chickens hatched from T. cruzi-inoculated eggs. kDNA incorporated into the chicken germline was inherited through the F2 generation in the absence of persistent infection. kDNA integration represents a potential cause for the autoimmune response that develops in a percentage of chronic Chagas patients, which can now be approached experimentally.