The conventional treatment for toxoplasmosis with pyrimethamine and sulfadiazine shows toxic effects to the host, and it is therefore necessary to search for new drugs. Some studies suggest the use of statins, which inhibit cholesterol synthesis in humans and also the initial processes of isoprenoid biosynthesis in the parasite. Thus, the objective of this study was to evaluate the activity of the statins pravastatin and simvastatin in HeLa cells infected in vitro with the RH strain of T. gondii. HeLa cells (1×10) were infected with T. gondii tachyzoites (5×10) following two different treatment protocols. In the first protocol, T. gondii tachyzoites were pretreated with pravastatin (50 and 100μg/mL) and simvastatin (1.56 and 3.125μg/mL) for 30min prior to infection. In the second, HeLa cells were first infected (5×10) with tachyzoites and subsequently treated with pravastatin and simvastatin for 24h at the concentrations noted above. Initially, we evaluated the cytotoxicity of drugs by the MTT assay, number of tachyzoites adhered to cells, number of infected cells, and viability of tachyzoites by trypan blue exclusion. The supernatant of the cell cultures was collected post-treatment for determination of the pattern of Th1/Th2/Th17 cytokines by cytometric bead array. There was no cytotoxicity to HeLa cells with 50 and 100μg/mL pravastatin and 1.56 and 3.125μg/mL simvastatin. There was no change in the viability of tachyzoites that received pretreatment. Regarding the pre- and post-treatment of the cells with pravastatin and simvastatin alone, there was a reduction in adhesion, invasion and proliferation of cells to T. gondii. As for the production of cytokines, we found that IL-6 and IL-17 were significantly reduced in cells infected with T. gondii and treated with pravastatin and simvastatin, when compared to control. Based on these results, we can infer that pravastatin and simvastatin alone possess antiproliferative effects on tachyzoites forms of T. gondii, giving these drugs new therapeutic uses.
Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and mainly spreads through the respiratory tract, which it then uses to reach several organs. The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches.
O objetivo deste estudo consistiu em analisar o perfil clínico de pacientes positivos para tuberculose através de um estudo epidemiológico, descritivo e retrospectivo, com base em dados secundários contidos em prontuários dos pacientes atendidos no Hospital Universitário de Londrina compreendendo de janeiro de 2010 a dezembro de 2014. Dos prontuários disponíveis para a análise no momento de estudo 86 casos eram positivos para tuberculose, sendo a maioria do sexo masculino (65/76%) com faixa etária compreendida entre 2 e 91 anos. Os principais sinais clínicos apresentados foram tosse (50/58%), febre (45/52%) e perda de peso (34/40%). Em relação à forma clínica, 58/67% dos pacientes apresentaram a forma pulmonar, e 28/33% a forma não pulmonar. Casos positivos para tuberculose em associação com HIV/AIDS corresponderam a 32/37%. Também foram relatados hábitos prejudiciais dos pacientes nos quais 30/34% eram tabagistas, 20/23% usuários de drogas e 14/16% etilistas. Diante da escassez de dados publicados referentes à tuberculose na nossa região e sua relevância para a saúde pública, nosso estudo contribui com os aspectos epidemiológicos principalmente em relação ao elevado número de casos de coinfecção com Vírus da Imunodeficiência Humana e pacientes com evolução a óbito, auxiliando assim, o desenvolvimento e implementação de campanhas ou projetos que visem o diagnóstico e tratamento precoce.
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