Aspectos Éticos Priorizados pela Revista Brasileira de Cancerologia / Ethical Aspects Prioritized by Revista Brasileira de Cancerologia / Aspectos Éticos Priorizados por la Revista Brasileira de Cancerologia

A Revista Brasileira de Cancerologia (RBC) preza pela integridade na pesquisa, estimulando a publicação de artigos desenvolvidos de forma respeitosa, honesta, rigorosa, transparente e aberta, além de envolver cuidado e respeito com os envolvidos. A revista viabiliza as correções em manuscritos sempre que estes afetarem substancialmente o significado ou a interpretação dos dados, mas que não comprometam os resultados ou conclusões gerais do artigo. Além disso, disponibiliza as retratações de um manuscrito indicadas por diversas razões, incluindo publicação duplicada, plágio, práticas de investigação não éticas. Sendo um periódico financiado pelo governo federal, a RBC não reproduz nem divulga anúncios publicitários em seus artigos ou em seu website, concentrando sua atuação na divulgação do conhecimento científico, com vistas ao aprimoramento dos serviços oferecidos pelo Sistema Único de Saúde (SUS) e por outros sistemas nacionais de saúde. Dentro de rígidos princípios éticos, a RBC segue crescendo tanto na publicação como no alcance nacional e internacional de seus artigos, expandindo pela ciência aberta a geração de novas práticas destinadas à prevenção e ao controle do câncer no cenário brasileiro e no contexto global.

Os 75 Anos da RBC e o Desafio da Ciência Aberta / The 75 Years of RBC and the Challenge of Open Science / Los 75 Años de RBC y el Desafío de la Ciencia Abierta

A Revista Brasileira de Cancerologia (RBC) representa um marco na editoração científica nas áreas do controle do câncer no Brasil. Sua história teve início em 1941, quando o Decreto-Lei n.º 3.643, de 23 de setembro de 19411, instituiu, no então Departamento Nacional de Saúde do Ministério da Educação e Saúde, o Serviço Nacional de Câncer e criou uma revista científica de cancerologia. No entanto, somente em setembro de 1947, foi publicado o seu primeiro número na intenção de divulgar, à comunidade acadêmica, conhecimentos no campo da cancerologia. Nas publicações da época, a RBC apresentava não somente artigos científicos e relatos de casos clínicos, mas também notícias relacionadas ao tema, material de divulgação de congressos e seminários, sessão de "perguntas e respostas", discursos completos do ministro da Saúde em eventos da área de câncer e saúde pública, além de anúncios de auxílios financeiros em pesquisa. Com o tempo, a RBC teve a sua importância e manutenção ainda mais valorizadas, e, em agosto de 1968, foi criado o Corpo Editorial, visando ao direcionamento e à indicação de pautas das futuras publicações. Até então, a revista trabalhava somente com redatores permanentes. Em 1982, buscando mais visibilidade, a revista foi indexada na base de dados denominada Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Apesar do aperfeiçoamento do seu projeto editorial, e de ter se tornado um grande veículo de comunicação científica na área da cancerologia no país, poucos avanços aconteceram em busca de uma maior internacionalização e indexação em outras bases de dados, até 2017

The Revista Brasileira de Cancerologia (RBC) is a milestone in scientific editing in the area of cancer control in Brazil. Its history started in 1941 after the issue of Decree-Law number 3,643, dated September 23, 19411 , which created the National Cancer Service and a cancerology scientific journal at the former National Department of Health of the Ministry of Education and Health. Nevertheless, only in 1947 the first edition came to light with the purpose of divulging knowledge in cancerology to the scholar community. Of the journals published at that time, RBC issued not only scientific articles and case reports but also theme-related news, press material for congresses and seminaries, Q&A (questions and answers) sections, complete addresses of the Ministry of Health in events on cancer and public health, further to notices about financial funding of researches2 . As time went by, RBC grew in importance and worth and the Editorial Board was created in August 1968 to put together guidelines and agenda of the upcoming editions. Until then, the journal counted only with permanent writers. In 1982, for more visibility, the journal was indexed at the database Latin American and Caribbean in Health Sciences (LILACS). Notwithstanding its editorial betterment and having stepped up to be a great vehicle of scientific communication in cancerology in the country, few advances in attempting a wider internationalization and indexation occurred at other databases until 2017

Tracoma: aspectos epidemiológicos no Brasil, 2009-2010 e perspectivas de controle / Trachoma: epidemiological aspects in Brazil, 2009-2010 and prospects for control

O tracoma é uma afecção inflamatória ocular crônica (ceratoconjuntivite crônica recidivante) que tem como agente etiológico a bactéria Chlamydia trachomatis. É reconhecido como importante problema de saúde pública, por ser esta a principal causa de cegueira evitável. Afeta 41 milhões de pessoas em todo o mundo das quais 1,3 milhões são cegas devido ao tracoma. A Organização Mundial de Saúde – OMS considera o tracoma endêmico em regiões subdesenvolvidas da África, Oriente Médio, Subcontinente Indiano, Sudeste da Ásia e nas Américas Central e Sul. No Brasil a prevalência conhecida no último inquérito nacional realizado no período de 2002 a 2008 detectou municípios com alta prevalência em todas as regiões do país e um coeficiente médio nacional de 5,1% de tracoma ativo. Este estudo tem por objetivo descrever o sistema de vigilância epidemiológica do tracoma no Brasil e os aspectos epidemiológicos da doença com base nas notificações no Sinan nos anos de 2009e 2010 e nos dados repassados diretamente a coordenação do agravo na SVS. Trata-se de um sistema de busca ativa de casos sob a responsabilidade dos estados e municípios que utiliza dados do último inquérito como base para identificação de foco. A abrangência do inquérito foi de 30% do total de municípios do país o que faz com que a maior parte dos municípios desconheça sua situação em relação ao tracoma. Nos dois anos analisados pouco mais de 300 municípios realizaram atividade de busca de casos, com destaque para os estados do Ceará, São Paulo, Bahia e Tocantins. Neste período foram examinadas 573.576 pessoas com 25.042 casos, o que corresponde a 4,4% de prevalência média. Com 80% dos inquéritos realizados em escolas da zona urbana, a maioria dos casos identificados foi de TF em crianças menores de 10 anos do sexo feminino. Os resultados demonstram que a doença permanece na população brasileira e que grande parte dos municípios não realiza o monitoramento de situação para a devida adoção de medidas preventivas. É fundamental estabelecer uma rotina de retroalimentação desses dados de forma ampla, de modo a impulsionar a utilização do Sinan como ferramenta oficial de notificação e implantação das ações de vigilância e controle do tracoma na rotina dos serviços de saúde com maior envolvimento dos gestores.

Trachoma is an inflammatory chronic eye disease (chronic relapsing keratitis) which has as etiological agent the bacteria Chlamydia trachomatis. Is recognized as an important public health problem that is the leading cause of preventable blindness. Affects 41 million people worldwide of which 1.3 million are blind because of trachoma. The World Health Organization – WHO considers the trachoma endemic in underdeveloped regions of Africa, the Middle East, the Indian subcontinent, Southeast Asia and Central and South America. In Brazil the prevalence known in the last national survey conducted from 2002 to 2008 found municipalities with high prevalence in all regions of the country and a national average of 5.1 coefficient of active trachoma. This study aims to describe the epidemiological surveillance system of trachoma in Brazil and epidemiological aspects of the disease on the basis of the notifications at Sinan in the years 2009 and 2010 and in data transferred directly coordinating the further SVS. It is a system of active search for cases under the responsibility of the States and municipalities that uses data from the latest survey as the basis for identification of focus. The scope of the investigation was of 30% of the total municipalities in the country which causes most municipalities don't know their situation in relation to trachoma. In the two years was considered little more than 300 municipalities carried out case search activity, especially for the States of Ceará, Bahia, São Paulo, and Tocantins. In this period were examined 573,576 people with 25,042 cases, which correspond to the average prevalence of 4.4%. With 80% of surveys conducted in schools in the urban area, most cases TF was identified in children younger than 10 years female. The results show that the disease remains in the Brazilian population and that much of the municipalities does not perform monitoring situation due to the adoption of preventive measures. It is essential to establish a routine of feedback of the data broadly, so as to boost the use of Sinan as official notification and deployment tool for surveillance and control of trachoma in the routine of health services with greater involvement of managers.

Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies.

Chagas disease, which is caused by the intracellular parasite Trypanosoma cruzi, is a neglected illness with 12-14 million reported cases in endemic geographic regions of Latin America. While the disease still represents an important public health problem in these affected areas, the available therapy, which was introduced more than four decades ago, is far from ideal due to its substantial toxicity, its limited effects on different parasite stocks, and its poor activity during the chronic phase of the disease. For the past 15 years, our group, in collaboration with research groups focused on medicinal chemistry, has been working on experimental chemotherapies for Chagas disease, investigating the biological activity, toxicity, selectivity and cellular targets of different classes of compounds on T. cruzi. In this report, we present an overview of these in vitro and in vivo studies, focusing on the most promising classes of compounds with the aim of contributing to the current knowledge of the treatment of Chagas disease and aiding in the development of a new arsenal of candidates with anti-T. cruzi efficacy.

Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies

Chagas disease, which is caused by the intracellular parasite Trypanosoma cruzi, is a neglected illness with 12-14 million reported cases in endemic geographic regions of Latin America. While the disease still represents an important public health problem in these affected areas, the available therapy, which was introduced more than four decades ago, is far from ideal due to its substantial toxicity, its limited effects on different parasite stocks, and its poor activity during the chronic phase of the disease. For the past 15 years, our group, in collaboration with research groups focused on medicinal chemistry, has been working on experimental chemotherapies for Chagas disease, investigating the biological activity, toxicity, selectivity and cellular targets of different classes of compounds on T. cruzi. In this report, we present an overview of these in vitro and in vivo studies, focusing on the most promising classes of compounds with the aim of contributing to the current knowledge of the treatment of Chagas disease and aiding in the development of a new arsenal of candidates with anti-T. cruzi efficacy.

Different cell death pathways induced by drugs in Trypanosoma cruzi: an ultrastructural study.

Electron microscopy has proven to be a reliable and essential tool to determine morphological alterations and target organelles in the investigation of new drugs for Chagas disease. In this review, we focused on evaluating different agents that induce death of Trypanosoma cruzi, i.e. lysophospholipids analogues, naphthoquinones and derivatives, cytoskeletal inhibitors and natural products. Apoptosis-like presents as morphological characteristics DNA fragmentation, membrane blebbing and apoptotic body formation. Autophagy involves autophagosome formation, with the appearance of membranes surrounding organelles and cytosolic structures. Necrosis causes the loss of osmotic balance, an increase of cytoplasmic vacuolization and plasma membrane disruption. Mitochondrion appears as a central checkpoint in both apoptosis and necrosis. Our evidences of ultrastructural changes to T. cruzi treated with the different classes of compounds point to dramatic mitochondrial alterations and similar autophagic phenotypes. Lysophospholipid analogues interfere in the lipid biosynthesis in epimastigotes, altering the amount of both phospholipids and sterols, and consequently the physical properties of the membrane. Naphthoquinone derivatives led to a strong DNA fragmentation in trypomastigotes and to the release of cysteine proteases from reservosomes to cytosol in epimastigotes, starting a proteolytic process which results in parasite death. The susceptibility of reservosomes was also observed in parasites treated with propolis, suggesting impairment of lipid metabolism, compromising membrane fluidity and leading to lysis. The cytoskeletal agents blocked mitosis of epimastigotes, arresting cell cycle and impairing the parasite proliferation. The variety of drug stimuli converge to the same pathway of death suggests an intense cross-talking between the three types of PCD in the protozoa.

The effect of Bulgarian propolis against Trypanosoma cruzi and during its interaction with host cells.

Propolis has shown activity against pathogenic microorganisms that cause diseases in humans and animals. The ethanol (Et-Blg) and acetone (Ket-Blg) extracts from a Bulgarian propolis, with known chemical compositions, presented similar activity against tissue culture-derived amastigotes. The treatment of Trypanosoma cruzi-infected skeletal muscle cells with Et-Blg led to a decrease of infection and of the intracellular proliferation of amastigotes, while damage to the host cell was observed only at concentration 12.5 times higher than those affecting the parasite. Ultrastructural analysis of the effect of both extracts in epimastigotes revealed that the main targets were the mitochondrion and reservosomes. Et-Blg also affected the mitochondrion-kinetoplast complex in trypomastigotes, offering a potential target for chemotherapeutic agents.

The effect of Bulgarian propolis against Trypanosoma cruzi and during its interaction with host cells

Propolis has shown activity against pathogenic microorganisms that cause diseases in humans and animals. The ethanol (Et-Blg) and acetone (Ket-Blg) extracts from a Bulgarian propolis, with known chemical compositions, presented similar activity against tissue culture-derived amastigotes. The treatment of Trypanosoma cruzi-infected skeletal muscle cells with Et-Blg led to a decrease of infection and of the intracellular proliferation of amastigotes, while damage to the host cell was observed only at concentration 12.5 times higher than those affecting the parasite. Ultrastructural analysis of the effect of both extracts in epimastigotes revealed that the main targets were the mitochondrion and reservosomes. Et-Blg also affected the mitochondrion-kinetoplast complex in trypomastigotes, offering a potential target for chemotherapeutic agents.

Treatment of Trypanosoma cruzi-infected mice with propolis promotes changes in the immune response.

Ethanol extract of Bulgarian propolis (Et-Blg) was administered by oral route in doses ranging from 25 to 100mg/kg body weight in experimental Trypanosoma cruzi-infected Swiss mice. Treatment with 50mg Et-Blg/kg body weight/day led to a decrease in parasitemia and showed no hepatic or renal toxic effect. Treatment with Et-Blg led to a decrease in the spleen mass and modulated the initial inflammatory reaction as demonstrated by analysis of the leukocyte profile in peripheral blood, quantification of T cells subsets, and phenotypic markers in the spleen. Preferential expansion of CD8(+) and partial inhibition in the increase of CD4(+)CD69(+) and CD8(+)CD69(+) in CD4(+)CD44(+) and CD8(+)CD44(+) and in the decrease of CD8(+)CD62L in Trypanosoma cruzi-infected mice were also observed. Taken together, our data indicate that treatment of Trypanosoma cruzi-infected mice with Et-Blg interferes with the basic properties of immune cells.

Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle.

Propolis is a bee product, which has long been used in folk medicine for the management of different diseases. In this study we evaluated the analgesic and anti-inflammatory effects of a standard ethanolic extract of Bulgarian propolis (Et-Blg) in mice and its in vitro effect on airway smooth muscle. Et-Blg inhibited acetic acid-induced abdominal contortions with an ID(50) = 7.4 +/- 0.7 mg. kg(-1). In the formalin test, the extract caused a significant reduction in pain in mice treated with 100 mg. kg(-1) Et-Blg during the neurogenic phase and for the inflammatory phase with all doses of the extract, with an ID(50) = 2.5 +/- 0.4 mg. kg(-1). Et-Blg inhibited also the capsaicin-induced ear edema in mice; however, this extract was ineffective when assessed in the tail-flick and hot-plate thermal assays. The analgesic effect of Et-Blg was associated with the inhibition of inflammatory responses and not to a simple irritation of nervous terminals. In vitro, this extract inhibited the contraction of trachea smooth muscle induced by histamine (IC(50) = 50 +/- 5 microg. mL(-1)), capsaicin (IC(50) = 26.8 +/- 3 microg. mL(-1)), 80 mM KCl (IC(50) = 27.8 +/- 3 microg. mL(-1)), and carbachol (IC(50) = 54 +/- 2 microg. mL(-1)).

Flavonoids and trypanocidal activity of Bulgarian propolis.

Acetone and ethanol extracts of two Bulgarian propolis samples (Bur and Lov) were investigated by high temperature high resolution gas chromatography coupled to mass spectrometry (HT-HRGC-MS), and their activity against Trypanosoma cruzi was evaluated. The ethanol extracts--Et-Bur and Et-Lov--showed similar composition, with a high content of flavonoids, and strong inhibitory activity against T. cruzi proliferative epimastigotes, which were more susceptible than trypomastigotes. In the presence of blood, the activity of Et-Bur or Et-Lov against trypomastigotes was similar to that of the standard drug, crystal violet. Both extracts also showed similar and significant activity against Staphylococcus aureus and Candida albicans, while being inactive against Escherichia coli. The acetone extract, Ket-Bur, was more active than Et-Bur against both forms of T. cruzi.