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listelement.badge.dso-type Item , A novel substrate for arrhythmias in Chagas disease(Universidade Federal de Minas Gerais, 2021) Artur Santos-Miranda; Julliane Vasconcelos Joviano-Santos; Jaqueline Oliveira Sarmento; Alexandre Costa; Allysson Thiago Cramer Soares; Fabiana Simão Machado; Jader dos Santos Cruz; Danilo Roman-CamposBackground: Chagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of CD there are still relevant open questions to be addressed. In the present investigation we aimed to evaluate the contribution of the Na+/Ca2+ exchanger (NCX) in the electrical remodeling of isolated cardiomyocytes from an experimental murine model of chronic CD. Methodology/Principal findings: Male C57BL/6 mice were infected with Colombian strain of Trypanosoma cruzi. Experiments were conducted in isolated left ventricular cardiomyocytes from mice 180–200 days post-infection and with age-matched controls. Whole-cell patch-clamp technique was used to measure cellular excitability and Real-time PCR for parasite detection. In current-clamp experiments, we found that action potential (AP) repolarization was prolonged in cardiomyocytes from chagasic mice paced at 0.2 and 1 Hz. After-depolarizations, both subthreshold and with spontaneous APs events, were more evident in the chronic phase of experimental CD. In voltage-clamp experiments, pause-induced spontaneous activity with the presence of diastolic transient inward current was enhanced in chagasic cardiomyocytes. AP waveform disturbances and diastolic transient inward current were largely attenuated in chagasic cardiomyocytes exposed to Ni2+ or SEA0400. Conclusions/Significance: The present study is the first to describe NCX as a cellular arrhythmogenic substrate in chagasic cardiomyocytes. Our data suggest that NCX could be relevant to further understanding of arrhythmogenesis in the chronic phase of experimental CD and blocking NCX may be a new therapeutic strategy to treat arrhythmias in this condition.listelement.badge.dso-type Item , Multifunctionality of βCD/Ofloxacin and HPβCD/Ofloxacin Complexes: improvement of the antimicrobial activity and apoptosis induction on lung adenocarcinoma A549 cells(Universidade Federal de Minas Gerais, 2020) Bolivar Ralisson Amaro; Caio César de Souza Alves; Gabriella Freitas Ferreira; Paloma Esteves de Carvalho; Jeferson Gomes da Silva; Cleonice Souza; Oswaldo Cardoso Jr.; Alessandra de Paula Carli; Fabiana Simão Machado; Ângelo Márcio Leite Denadai; Sandra Bertelli Ribeiro CastroThe ofloxacin (OFLOX) is a second-generation synthetic antibiotic that can be classified as a multifunctional drug, but is a poorly soluble drug, which influences its efficiency. The inclusion complexes of OFLOX with β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) can improve the chemical characteristics of the drug; however, studies showing the biological activity of these inclusion complexes are still scarce. The present work aimed to investigate the multifunctionality of the OFLOX and their inclusion complexes. Thus, the 1:1 βCD/OFLOX or HPβCD/OFLOX were prepared and analyzed by Fourier transform infrared spectroscopy (FTIR), thermogravimetric and differential thermal analysis (TGA and DTA), 1 H nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC). The antitumor and antibacterial effects were assessed. The results confirm the formation of the inclusion complexes, which had lower minimum inhibitory concentration (MIC) values, higher cytotoxicity and promoted the apoptosis. The present study showed, for the first time, the promising effects of the inclusion complexes as antitumor, improving the biological activities of the uncomplexed ofloxacin.listelement.badge.dso-type Item , Chagas Disease in the New York City Metropolitan Area(Universidade Federal de Minas Gerais) Cristal Zheng; Orlando Quintero; Elizabeth Knackmuhs Revere; Michael Oey; Fabiola Espinoza; Yoram Andrew Puius; Diana Ramirez-Baron; Carlos Salama; Luís Hidalgo; Fabiana Simão Machado; Omar Saeed; Jooyoung Shin; Snehal Patel; Christina Coyle; Herbert TanowitzBackground Chagas disease, caused by the parasite Trypanosoma cruzi, once considered a disease confined to Mexico, Central America, and South America, is now an emerging global public health problem. An estimated 300 000 immigrants in the United States are chronically infected with T. cruzi. However, awareness of Chagas disease among the medical community in the United States is poor. Methods We review our experience managing 60 patients with Chagas disease in hospitals throughout the New York City metropolitan area and describe screening, clinical manifestations, EKG findings, imaging, and treatment. Results The most common country of origin of our patients was El Salvador (n = 24, 40%), and the most common detection method was by routine blood donor screening (n = 21, 35%). Nearly half of the patients were asymptomatic (n = 29, 48%). Twenty-seven patients were treated with either benznidazole or nifurtimox, of whom 7 did not complete therapy due to side effects or were lost to follow-up. Ten patients had advanced heart failure requiring device implantation or organ transplantation. Conclusions Based on our experience, we recommend that targeted screening be used to identify at-risk, asymptomatic patients before progression to clinical disease. Evaluation should include an electrocardiogram, echocardiogram, and chest x-ray, as well as gastrointestinal imaging if relevant symptoms are present. Patients should be treated if appropriate, but providers should be aware of adverse effects that may prevent patients from completing treatment.listelement.badge.dso-type Item , SOCS2 Is Critical for the Balancing of Immune Response and Oxidate Stress Protecting Against Acetaminophen-Induced Acute Liver Injury(Universidade Federal de Minas Gerais, 2019) Renata Monti Rocha; Allysson Thiago Cramer Soares; Paulo Gaio Leite; Maisa Mota Antunes; Rafaela Vaz Sousa Pereira; Andreia Barroso; Celso Martins Queiroz-Junior; Bruna Araujo David; Mauro Martins Teixeira; Gustavo Batista Menezes; Fabiana Simão MachadoO paracetamol (APAP) geralmente é seguro quando administrado em doses terapêuticas; no entanto, a sobredosagem de APAP pode levar a lesões hepáticas graves. O APAP pode causar danos diretos aos hepatócitos e estimular uma resposta inflamatória que leva ao estresse oxidativo. O supressor da sinalização de citocinas (SOCS) 2 modula a sinalização de citocinas e fatores de crescimento e desempenha um papel na regulação dos processos celulares hepáticos. Nosso estudo avaliou o papel do SOCS2 na lesão hepática induzida por APAP. A administração de uma dose tóxica (600 mg/kg) de APAP causou necrose hepática significativa em camundongos selvagens (WT). Em camundongos com deficiência de SOCS2 (SOCS2 −/−) , observou-se significativamente mais necrose, recrutamento de neutrófilos e expressão da quimiocina CXCL-1, ativa em neutrófilos. A expressão de citocinas pró-inflamatórias, como TNF-α e IL-6, estava elevada, enquanto a expressão de citocinas anti-inflamatórias, IL-10 e TGF-β, estava diminuída. In vitro , hepatócitos SOCS2 −/− expressaram mais p-NF-κB e produziram mais ROS do que hepatócitos WT quando expostos a APAP. Hepatócitos SOCS2 −/− foram mais sensíveis à morte celular na presença de IL-6 e peróxido de hidrogênio. A administração de catalase in vitro e in vivo resultou em uma redução acentuada da morte celular/camundongo e necrose no grupo SOCS2 −/− . Demonstramos que SOCS2 tem um papel protetor no fígado, controlando mecanismos pró-oxidativos e inflamatórios induzidos por APAP.listelement.badge.dso-type Item , Oral and oropharyngeal cancer: time from first symptoms to treatment initiation and associated factors(Universidade Federal de Minas Gerais)