https://repositorio.ufu.br/handle/123456789/5488 Mon, 12 Oct 2026 23:02:56 GMT 2026-10-12T23:02:56Z https://repositorio.ufu.br/handle/123456789/50516 Title: Influência da infecção por Toxoplasma gondii na interação entre vilos placentários humanos e astrócitos (U-373 MG) Abstract: Congenital toxoplasmosis, caused by the protozoan Toxoplasma gondii, can result in significant alterations in the fetal central nervous system. Although the placenta constitutes an essential barrier against vertical transmission, it also acts as an immunologically active organ capable of releasing mediators that may influence fetal tissues. This study investigated the role of soluble factors produced by first- and third-trimester human placental villi, infected or not with T. gondii, in modulating the response of U-373 MG cells, used as an astrocyte-like cell model. Conditioned media obtained from placental explants were used to evaluate cell viability, production of reactive oxygen species (ROS) and cytokines, ICAM-1 expression, and cell susceptibility to parasite adhesion, invasion, and proliferation. Third-trimester placental villi showed greater susceptibility to T. gondii infection than first-trimester villi. Placental infection also altered the profile of soluble mediators, promoting changes in the production of pro- and anti-inflammatory cytokines. Conditioned media from infected villi reduced U-373 MG cell viability and increased ROS production, indicating that factors released by the infected placenta can alter the cellular state even in the absence of direct contact with the parasite. In addition, gestational age-dependent effects on susceptibility to infection were observed. Conditioned medium from first-trimester villi restricted T. gondii proliferation, whereas conditioned medium from infected third-trimester villi favored parasite invasion and intracellular proliferation. ICAM-1 expression and parasite adhesion were also differentially modulated between gestational periods, with increased ICAM-1 expression associated with conditioned medium from infected third-trimester villi. Collectively, these findings demonstrate that the infected placenta actively influences astrocyte-like cells and that this communication is dependent on gestational stage. These results suggest that the pathogenesis of congenital toxoplasmosis may involve not only the direct effects of parasite presence in the central nervous system, but also the action of soluble mediators originating at the maternal-fetal interface, highlighting a potential functional placenta–brain communication during T. gondii infection. Thu, 24 Sep 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/50516 2026-09-24T00:00:00Z https://repositorio.ufu.br/handle/123456789/50515 Title: Toxoplasma gondii na interface materno-fetal: prospecção de novos candidatos terapêuticos e efeitos de vesículas extracelulares placentárias sobre células endoteliais cerebrais Abstract: Toxoplasmosis is a disease caused by the protozoan Toxoplasma gondii. Infection during pregnancy can lead to congenital toxoplasmosis, which is associated with severe outcomes, such as neurological problems, fetal abnormalities, stillbirths, and spontaneous abortion. Current treatment options for congenital toxoplasmosis have several limitations, including low efficacy during the chronic phase of the disease and potential fetal toxicity, with bone marrow suppression and teratogenic effects. Therefore, there is an urgent need for more effective and safer therapeutic alternatives. In Chapter I, three compounds from the Medicines for Malaria Venture Pathogen Box were evaluated: MMV675968, MMV022478, and MMV021013, regarding their ability to control T. gondii infection in human trophoblast cells (BeWo) and third-trimester placental villous explants. The toxicity of the compounds, their effects on the parasite's lytic cycle (including adhesion and invasion), changes in parasite morphology, and the host immune response through cytokine quantification were evaluated. Non-toxic concentrations of the three compounds irreversibly inhibited parasite proliferation and interfered with the initial stages of the lytic cycle. In addition, treated T. gondii tachyzoites exhibited membrane disruption, cytoplasmic degradation, and organelle disorganization. The cytokine profile indicated that treatment with the compounds promoted an anti-inflammatory immune response, mainly through a reduction in IL-8 levels. Importantly, these compounds also effectively controlled T. gondii infection in human placental explants without inducing cytotoxicity. These findings support the potential of MMV675968, MMV022478, and MMV021013 as promising drug candidates for the treatment of congenital toxoplasmosis. MMV021013 stands out as the most promising compound, combining predicted high gastrointestinal absorption and blood-brain barrier permeability, with no predicted mutagenic, tumorigenic, irritant, or reproductive effects. In the second chapter, drugs included in the Relação Nacional de Medicamentos Essenciais (RENAME) were evaluated regarding their potential for drug repurposing in the treatment of congenital toxoplasmosis. Among the drugs investigated, metronidazole and acyclovir exhibited a favorable selectivity profile, with antiparasitic activity associated with the preservation of BeWo cell viability, standing out as candidates for further studies. In the third chapter, the influence of extracellular vesicles derived from placental explants exposed to the soluble antigen of T. gondii tachyzoites (STAg) on human brain microvascular endothelial cells was investigated. Vesicles obtained from placental villi exposed to STAg exhibited changes in their characteristics, including increased size and reduced Syncytin-1 expression. In addition, STAg treatment contributed to lower particle uptake by endothelial cells and influenced the inflammatory response of recipient cells, with changes in IL-6 production, highlighting the involvement of these vesicles in intercellular communication. Taken together, the results of the three chapters expand our understanding of the potential of drug repurposing for the control of congenital toxoplasmosis and the mechanisms of communication between the placenta and the cerebral endothelium. Fri, 25 Sep 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/50515 2026-09-25T00:00:00Z https://repositorio.ufu.br/handle/123456789/49418 Title: Pesquisa do agente da Febre Maculosa Rickettsia parkeri cepa Mata Atlântica no Estado de Minas Gerais Abstract: Ticks are hematophagous ectoparasites responsible for transmitting diseases to humans and an-imals. Among these diseases, Brazilian Spotted Fever, caused by Rickettsia rickettsii, stands out due to its high lethality when diagnosed late. Confirmed cases of this disease are closely associated with ticks of the genus Amblyomma, which represents the greatest diversity of ixodid species in Brazil. On the other hand, other species of the genus Rickettsia, such as Rickettsia parkeri Atlantic rainforest strain (ARF), may cause milder and frequently underdiagnosed clin-ical manifestations, although they still hold epidemiological importance. Minas Gerais is a state of large geographic proportions, with areas that favor the circulation of both bacteria, as well as their vectors. However, R. parkeri ARF , associated with its main vector Amblyomma ovale, had never been reported in this state. In this study, divided into two articles, we evaluated in the state of Minas Gerais the exposure of dogs, important sentinels of this disease, to the rick-ettsial antigens, as well as the presence of genetic material in ticks, in addition to assessing the seasonality of A. ovale, the main vector of R. parkeri ARF. These observations allowed us to conclude that the vector A. ovale shows higher frequency and abundance in spring, with greater intensity in November. Furthermore, the results provided evidence of exposure to rickettsial antigens in dogs from rural properties in the state of Minas Gerais, Brazil. Furthermore, the presence of R. parkeri ARF DNA was detected in two A. ovale ticks, constituting the first report of this bacterium associated with this tick in Minas Gerais. Thu, 26 Mar 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/49418 2026-03-26T00:00:00Z https://repositorio.ufu.br/handle/123456789/48402 Title: Infecções relacionadas à assistência à saúde em unidades de terapia intensiva de adultos no Brasil: Uma abordagem multicêntrica Abstract: Healthcare-associated infections (HAIs) remain one of the major global health challenges, particularly in low- and middle-income countries such as Brazil, where the clinical and economic impact is exacerbated by the high prevalence of multidrug-resistant microorganisms. This thesis, composed of three interrelated articles, integrates different aspects of the epidemiology and dissemination of Klebsiella pneumoniae and Acinetobacter baumannii resistant to carbapenems, as well as a discussion of the clinical impact of HAIs in Brazilian intensive care units (ICUs). The first article aimed to determine the point prevalence of HAIs and identify factors associated with microbiologically confirmed infections in adult ICUs across Brazil. This multicenter study, conducted in 57 ICUs from different regions of the country, included 664 patients, of whom 47.7% had HAIs, with 68.1% acquired in the ICU. Only 47.2% of these infections were microbiologically confirmed. Mechanical ventilation and the use of polymyxins were identified as independent risk factors. The etiology of pneumonia, urinary tract infections, and bloodstream infections (BSIs) was predominantly associated with Pseudomonas aeruginosa and Acinetobacter baumannii; Candida spp.; and coagulase-negative Staphylococcus, respectively. The second article investigated the dissemination of resistance genes (by polymerase chain reaction – PCR) and pulsotypes (by pulsed-field gel electrophoresis – PFGE) in Klebsiella pneumoniae carbapenemase- producing (KPC) and Acinetobacter baumannii oxacillinase-producing (OXA-23) isolates from hospitals located in the North, Northeast, Southeast, and Central-West regions of Brazil. The blaOXA-23 and blaKPC genes were detected in 88.1% and 83.3% of A. baumannii and K. pneumoniae isolates, respectively, and all displayed multidrug- resistant profiles. Eleven distinct genotypes of A. baumannii were identified, with clone E detected in the Southeast (2016) and Central-West (2019) regions. No inter-regional dissemination of identical K. pneumoniae pulsotypes was observed. The third article, presented as a letter complementing a previous international study, expanded the discussion on the clinical impact of carbapenem-resistant Klebsiella pneumoniae infections. As part of this thesis, a letter was written discussing the study by Shao et al. (2024), which analyzed bloodstream infections in pediatric intensive care units in China. Our contribution compared those findings with data from our multicenter cohort of adult ICU patients with multidrug-resistant K. pneumoniae infections, emphasizing the high mortality associated with carbapenem-resistant strains. The letter highlighted similarities between pediatric and adult populations regarding risk factors and clinical outcomes, particularly in severe infections such as BSIs and pneumonia, and reinforced the urgent need for targeted strategies to combat antimicrobial resistance in both patient groups. Taken together, the three studies provide a comprehensive overview of HAIs in Brazilian ICUs, revealing their high prevalence, regional dissemination, and clinical impact, particularly regarding infections caused by multidrug-resistant K. pneumoniae. The findings underscore the importance of strengthening epidemiological surveillance policies, microbiological diagnosis, and rational antimicrobial use, as well as promoting the integration of national and international data to address the global challenge of bacterial resistance. Tue, 10 Feb 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/48402 2026-02-10T00:00:00Z