BackgroundHeart disease progression occurs in 30% of patients with chronic Trypanosoma cruzi infection. Supplementation with selenium (Se) in animal model of T. cruzi infection produced promising results. There is evidence that patients with Chagas heart disease have lower Se levels than healthy individuals and patients with T. cruzi infection without of cardiac disease. The aim of this investigation is to estimate the effect of Se treatment on prevention of heart disease progression in patients with chagasic cardiopathy.MethodsThe Selenium Treatment and Chagasic Cardiopathy trial is a superiority, double-blind, placebo-controlled, randomized clinical trial. The eligibility criteria are as follows: (1) a Chagas disease diagnosis confirmed by serology; (2) segmental, mild or moderate global left ventricular systolic dysfunction; and (3) age between 18 and 65 years. The exclusion criteria are as follows: (1) pregnancy, (2) diabetes mellitus, (3) tobacco use, (4) alcohol abuse, (5) evidence of nonchagasic heart disease, (6) depression, (7) dysphagia with evidence of food residues in the esophagus, (8) dysphagia with weight loss higher than 15% of usual weight in the last four months and/or (9) conditions that may result in low protocol adherence. The intervention will be 100 μg of sodium selenite once daily for 365 consecutive days compared to placebo. The following are the primary outcomes to be measured: (1) the trajectories of the left ventricular ejection fraction in the follow-up period; (2) reduction of heart disease progression rates, with progression defined as a 10% decrease in left ventricular ejection fraction; and (3) rate of hospital admissions attributable to dysrhythmia, heart failure or stroke due to Chagas disease. One hundred thirty patients will be randomly allocated into either the intervention or placebo group at a ratio of 1:1. The sequence allocation concealment and blinding were planned to be conducted with the strategy of numbered boxes. Both patients and health-care providers will remain blinded to the intervention groups during the 5 years of follow-up.DiscussionIf Se treatment reduces the progression of Chagas cardiopathy, the inclusion of this micronutrient in the daily diet can improve the therapeutic regimen for this neglected tropical disease at low cost.Trial registrationClinical Trials.gov ID: NCT00875173 (registered 20 October 20 2008).
uma revisão bibliográfica da imunologia da toxoplasmose ocular, que faz referência ao papel do IFN-γ no curso da infecção toxoplásmica ocular (1) . Gostaríamos de parabenizar os autores pelo artigo e aproveitar a oportunidade para retificar uma das citações, uma vez que ocorreu um grande equívoco quando os mesmos citam o artigo de nossa autoria "IFN-γ (+874 T/A) gene polymorphism is associated with retinochoroiditis toxoplasmosis susceptibility", publicado nas Memórias do Instituto Oswaldo Cruz. 2009;104(3):451-455 (2) . No artigo de sua Revista, os referidos autores, fazendo menção ao nosso artigo, registram: "Em um estudo com pacientes com retinocoroidite toxoplás-mica, não foram encontradas associações significativas deste polimorfismo com a ocorrência da doença, ao compararmos indivíduos infectados com e sem a doença". Em nosso estudo foi encontrada associação com diferença estatisticamente significativa entre os indivíduos com retinocoroidite toxoplásmica que apresentavam o genótipo AA (p-valor 0,014), numa frequência aumentada em relação aos seus controles, indivíduos soropositivos para o Toxoplasma gondii e sem lesão ocular.Sendo assim, solicitamos que os leitores e os autores do artigo soubessem que houve uma interpretação completamente errônea de nossos resultados, o que, lamentavelmente, pode comprometer não somente a citação do estudo original por outros autores, em futuras publicações, como também a credibilidade de tão conceituada Revista.Certas de termos tal equívoco devidamente retificado, subscrevemo-nos.
Introduction: Drug repurposing is the promptest way to obtain an effective drug during a global public health emergency as the spread of Zika virus that is associated with the congenital syndrome. Why the virus reaches the fetus is still unclear, however the placenta represents an important route of transmission, since the virus was detected in vivo and in vitro human and murine placenta. The fetal infection may occur by passing the virus through spaces created by lesions or inflammation that may break the placental barrier. Another hypothesis is that the virus crosses the placenta through infection of host cells, being possible the transmission of ZIKV to the fetus occur from sexual transmission. Despite the emerging severity caused by the ZIKV infection, there still no specific treatment for this disease. The antiparasitic and antiviral drug Annita® already approved through the Food and Drug Admistration and safe for pediatric use and for administration in pregnant women, being included in category B, could have activity against ZIKV due to broad aspect and affordable price. Objective: With this in mind our group evaluated the antiviral effect this drug in chorionic cells of primary culture human placenta and in cervix human cells, two important targets of infection, in comparing to Vero cells from African green monkey and C6/36 cells from Aedes albopictus. Methodology: The antiviral effect was assessed by immunofluorescence, Plaque assay and RT-qPCR in cultures infected with ZIKV and treated with non-toxic concentrations of the drug for 48h. Results: Previous results using Vero cultures showed antiviral effect of drug only when the treatment was performed after the adsorption step. This treatment scheme revealed a dosedependent reduction of infection in chorionic cells at 79% at the concentration of 50 μg/ mL. Interestingly, in the cervix cells, at the concentration of 12 μg/mL already had a 95% of infection reduction. The EC50 values were 23±5μg/mL for chorionic cells and 6±0.4μg/mL for cervix cells. Analyzing the reduction of infectious particles, the concentration of 25 μg/ mL in the chorionic cells and 12 μg/mL in the cervix cells inhibited 100% of the progeny. In addition, the quantification of viral RNA copies/mL in the supernatant of the treated cultures with 50 μg/mL showed a reduction of 93% in chorionic cells and 87% in cervix cell cultures. However, in cells of the ZIKV-infected C6/36 mosquito line, the treatment did not reduce the number of infectious particles in the cultures supernatant, suggesting that the activity of this drug is related to the response of the host cells. Conclusion: The Annita® drug demonstrated good antiviral activity, which may be related to host cell response. Studies aimed at reusing drugs should be encouraged because they accelerate the discovery of drugs for the treatment of ZIKV infection, especially for infected pregnant women.
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