http://repositorio.ufc.br/handle/riufc/186 Tue, 16 Jun 2026 01:59:08 GMT 2026-06-16T01:59:08Z http://repositorio.ufc.br/handle/riufc/86408 Título: Avaliação da atividade de peptídeos derivados do veneno de Crotalus durissus terrificus sobre a criopreservação espermática Autor(es): Moura, Gabriel Acácio de Tipo: Tese Thu, 01 Jan 2026 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/86408 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86238 Título: Avaliação da atividade in vitro dos derivados sintéticos de N-ciclohexil 3-(3-metilfenil)1,2,4-oxadiazol-5-amina sobre a cepa y de Trypanosoma cruzi e um estudo de toxicidade in vivo Autor(es): Rocha, Yasmim Mendes Abstract: Chagas disease remains a significant public health problem in Latin America, primarily treated with Nifurtimox and Benznidazole. Despite initial proactive strategies, these medications have limitations, such as low efficacy in the chronic phase and adverse effects. In this context, heterocyclic compounds, such as 1,2,4-oxadiazole derivatives, have been investigated as potential therapeutic alternatives. This study aimed to evaluate the trypanocidal activity and toxicity of molecules 2a, 2f, and 2i against the Trypanosoma cruzi strain using in vitro, in silico, and in vivo assays. The results showed a concentration-dependent effect on epimastigote forms, with IC50 values of 31.4 µM, 44.4 µM, and 7.0 µM for 2a, 2f, and 2i, respectively. In trypomastigotes, LC50 values of 14.2 µM, 2.4 µM, and 2.6 µM were observed for these same molecules, in addition to a significant reduction in the amastigote load in infected cells. The selectivity index was 15, 5.8, 9.8, and 4.7 for molecules 2a, 2f, 2i, and benznidazole, respectively. Flow cytometry analyses indicated compromised cell integrity, induction of oxidative stress, and mitochondrial dysfunction, altering different targets of action of the molecules under study. Using free radical neutralization assays in solution, through antioxidant activity and acetylcholinesterase inhibition, the molecules under study showed a high capacity for scavenging free radicals. These findings suggest that such compounds may interfere with the redox balance of the parasite, contributing to oxidative stress and, consequently, to the observed antiparasitic effects. Subsequently, scanning electron microscopy revealed membrane alterations, cell rounding, or flagellar absence. Among the compositions evaluated, molecule 2a stood out for presenting a better balance between efficacy and selectivity in vitro, in addition to interactions developed with the cruzipain enzyme in in silico analyses. In in vivo assays with zebrafish, molecule 2a showed dose-dependent embryonic toxicity (LC50~15 µM); similar to bzn at higher concentrations, decreasing a specific cytotoxic potential. Taken together, these findings reinforce the potential of 1,2,4-oxadiazole derivatives as promising candidates for the development of new therapeutic strategies against Chagas disease, highlighting molecule 2a as a priority target for future studies. Tipo: Tese Thu, 01 Jan 2026 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/86238 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86220 Título: Efeito citoprotetor de nanopartículas poliméricas contendo resveratrol em modelo in vitro de doença de Parkinson induzida por rotenona: envolvimento da via Nrf2 Autor(es): Teixeira, Izabell Maria Martins Abstract: Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra, resulting in motor impairment, whose prevalence is expected to increase in the coming decades. Considering the limitations of current clinical treatment (levodopa), new therapeutic strategies are needed. Resveratrol (RSV) has antioxidant and anti-inflammatory properties, but its low bioavailability limits its clinical application, making nanoencapsulation a promising alternative. The aim of this study was to evaluate the in vitro protective effect of resveratrol polymeric nanoparticles (NP RSV) and the involvement of the Keap1/Nrf2/ARE pathway in a mimetic model of PD induced by rotenone (ROT). For in vitro assays, PC12 neuronal cells and astrocytes were pretreated with NP RSV, RSV, and dopamine (DA) for 1 hour, followed by exposure to ROT for 24 hours. Cell viability was assessed by the MTT assay. The pattern of cell death, reactive oxygen species production, and mitochondrial transmembrane potential (ΔΨm) were evaluated by flow cytometry assays. Cellular morphological changes were assessed by optical microscopy. In silico tests were performed to investigate the theoretical interaction of RSV with the Kelch and Brick-to-Brick (BTB) domains of the Keap1 protein. Gene expression of Nrf2 and HMOX, elements of the Keap1/Nrf2/ARE pathway, was performed by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). The results showed that ROT induced a reduction in cell viability, increased oxidative stress, depolarization of ΔΨm, and cell death by apoptosis; however, pretreatment with NP RSV was able to significantly protect the cells, preserving cell viability, reducing the formation of reactive oxygen species, maintaining mitochondrial function, and decreasing apoptosis. The protective effects of NP RSV were observed at concentrations of 1.56 µM, 0.78 µM, and 0.39 µM in PC12 cells and 6.25 µM, 3.12 µM, and 1.56 µM in astrocytes; while RSV showed a protective effect at concentrations of 12.5 µM, 6.25 µM, and 3.12 µM in both cell lines. DA (400 µM-100 µM) showed limited neuroprotective effects. Morphological analyses corroborated these findings, showing cellular changes and reduced cell density after exposure to ROT and maintenance of these characteristics when pretreated with NP RSV. In silico assays indicated a stable interaction between RSV and Keap1 protein, sustained by hydrogen bonds. Regarding gene expression, ROT promoted increased expression of NRF2 and HMOX-1, while pretreatment with NP RSV modulated this response. Together, the data indicate that NP RSVs exert a neuroprotective effect, acting in an integrated manner on the main mechanisms involved in the pathophysiology of PD, with emphasis on the modulation of the Keap1/Nrf2/ARE pathway. Thus, the present study contributes to the understanding of the molecular mechanisms associated with neuroprotection mediated by nanostructured systems, presenting scientific relevance. Tipo: Dissertação Thu, 01 Jan 2026 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/86220 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/84263 Título: Desfechos clínicos e implicações econômicas das infecções relacionadas à saúde em unidades de terapia intensiva: do leito à gestão Autor(es): Barroso, Lysrayane Kerullen David Abstract: Healthcare-Associated Infections (HAIS) represent one of the main challenges in hospitals, especially in Intensive Care Units (ICU), where the clinical severity of patients and invasive procedures increase the risk of complications. In addition to adverse clinical outcomes, HAIs impose a significant financial burden on health systems due to the use of broad-spectrum antimicrobials, intensive therapies, and prolonged hospital stays. In this context, it is essential to understand the economic impact of HAIs through clinical and care indicators that can support management and guide public health policies. This thesis aimed to analyze the clinical and economic impact of HAIs in Intensive Care Units to support improvements in care managementTo this end, complementary methodological strategies were developed: an integrative literature review on the costs associated with HAIs in ICU; an observational retrospective study based on 590 patients hospitalized with hospital-acquired pneumonia in Ceará; and a field study at the Hospital Regional Norte (HRN), where the epidemiological profile and clinical outcomes of ICU patients with HAIs were characterized, along with the measurement of hospital costs associated with these infections. Based on these data, an analysis of the correlation between clinical outcomes and costs was conducted, allowing for a deeper understanding of the magnitude of the problem at the institutional level. Finally, a critical analysis of health management challenges in the prevention and control of HAIs was carried out, emphasizing strategies for improving care quality and patient safety. The results showed that hospitalization costs for patients with HAIs can be up to four times higher, mainly due to longer hospital stays and the use of last-line antimicrobials. The observational study indicated elevated costs in pneumonia hospitalizations, particularly among the elderly. The field study at HRN revealed higher mortality rates, prolonged hospitalization, and significantly higher costs among patients with HAIs, with ventilator-associated pneumonia, urinary tract infections, and primary bloodstream infections being the most frequent. Moreover, multivariate analysis identified factors such as advanced age, sepsis, and the need for mechanical ventilation as independent predictors of mortality, substantially increasing hospital costs. These findings reinforce the importance of continuous epidemiological surveillance, adherence to HAI prevention protocols, and the integrated work of multiprofessional teams, highlighting the strategic role of hospital pharmacy in resource management. The use of clinical-economic indicators proved effective in measuring the impact of HAI, showing their potential to guide cost-effective interventions and managerial decisions. It is concluded that HAI are not only a clinical but also an economic and managerial problem. The integrated analysis of outcomes and costs provides a comprehensive approach that contributes to improving care quality and the sustainability of the health system. This study provides evidence to support managers and health professionals in implementing preventive strategies, monitoring, and rationalizing the use of resources, aiming to reduce the incidence and impact of HAI in the hospital setting. Tipo: Tese Wed, 01 Jan 2025 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/84263 2025-01-01T00:00:00Z