http://repositorio.ufc.br/handle/riufc/399 2026-04-13T19:53:14Z 2026-04-13T19:53:14Z Silva, Bruno Nascimento da http://repositorio.ufc.br/handle/riufc/85535 2026-03-28T18:42:35Z 2025-01-01T00:00:00Z

Título: Perfil clínico-epidemiológico das infecções causadas por Trichosporon spp. em um hospital pediátrico de referência e busca de novas estratégias de controle do crescimento fúngico Autor(es): Silva, Bruno Nascimento da Abstract: Invasive fungal infections (IFIs) involve contamination of the bloodstream and invasion of sterile tissues and/or organs and are considered highly relevant public health issues due to high morbidity and mortality rates. Trichosporon spp. are considered opportunistic fungi, as they take advantage of microbial dysbiosis and host immune imbalance to cause serious invasive infections. This study investigated the clinical and epidemiological profile of invasive infections by Trichosporon spp., as well as the impact of calcineurin and Hsp90 protein inhibition on the growth of this pathogen. The epidemiological study included 28 isolates of interest. Data from these patients were collected and analyzed regarding: age, sex, most prevalent species of the genus, distribution by hospital unit, reasons for care, use of invasive devices, clinical specimens from which pathogens were isolated, use of antimicrobials and other conditioning drugs, co-infection, and treatment measures – all of which were associated with the clinical outcome (discharge or death). The strains isolated and selected in the prospective phase (n=12) were studied for their ability to form biofilms and their sensitivity profile to amphotericin B (AMB), voriconazole (VRZ), and fluconazole (FLZ). The second phase of the work concerns the inhibition of calcineurin by the use of Cyclosporine A (CsA), against planktonic cells and biofilms of Trichosporon spp. strains in n=13 already contained in stock. These biofilms were formed in the presence of CsA at concentrations of 25 µg/mL, 50 µg/mL, and 100 µg/mL for the planktonic state and 50 µg/mL and 100 µg/mL for the biofilms. Subsequently, CsA at the same concentrations mentioned above were associated with the antifungals AMB (10 µg/mL), VRZ (50 µg/mL), and FLZ (64 µg/mL) and subjected to the same tests. The impact of CsA on the ultrastructure of the biofilms was evaluated by Scanning Electron Microscopy (SEM) both in isolation and in combination with the antifungals. Bioinformatics analyses were performed to investigate the antibiofilm potential caused by calcineurin inhibition in T. asahii. In the inhibition of Hsp90 using Radicicol (RAD), the strains were subjected to planktonic sensitivity testing and subsequently studied with mature biofilms (48h) exposed to RAD at concentrations of 6.25 µg/mL for T. asahii and 10 µg/mL for T. inkin. Then, the same concentrations of RAD in the mature biofilms were associated with AMB 4 µg/mL for T. asahii and 2 µg/mL for T. inkin and VRZ 0.125 µg/mL for an additional 24h in contact with the mature biofilm in vitro, the morphology of the biofilms was assessed by SEM, and virulence was evaluated using an experimental infection model with Galleria mellonella larvae. The epidemiological study showed that the most affected pediatric population over the years were boys, most of whom were admitted to Intensive Care Units (ICUs). Patients with neurological diseases and cancer; those using various invasive medical devices, such as feeding tubes; most samples isolated from urine; a significant portion used prophylactic antimicrobials; mortality rates are considerable; the most prevalent species is T. asahii; the strains obtained are capable of forming biofilms. CsA and RAD, isolated and in combination with antifungals, are able to inhibit the fungal growth of T. inkin and T. asahii in vitro and significantly alter the ultrastructure of biofilms. RAD is effective in treating infected G. mellonella larvae. These results suggest new and promising therapeutic targets for invasive trichosporonosis, considering the difficulty and resistance in treating these infections Tipo: Tese

2025-01-01T00:00:00Z Leite, Lindomagno Pessoa http://repositorio.ufc.br/handle/riufc/85424 2026-03-24T12:16:44Z 1998-01-01T00:00:00Z

Título: Estudo analítico da associação da doença de Hodkin com o vírus de Epstein-Barr em uma região tropical: Comparação com dados oriundos de pesquisas em regiões com distintos níveis de desenvolvimento social e econômico Autor(es): Leite, Lindomagno Pessoa Abstract: Many studies have shown that Hodgkin’s disease (HD) is associated with Epstein-Barr virus (EBV) in a substantial number of cases, and that in these cases EBV DNA is localized exclusively in Reed-Stemberg (RS) cells. In the present study, we carried out an analytic analysis in a sample with 50 HD cases from Ceara, Northeast Brazil. The sample was divided in two main groups: group aged less than 18 years old (infant-juvenile) and group aged more than 18 years old (adult). Chi-square (X2) test was performed to analyses the possible relation of EBV in each age group with the histopathologic subtypes of HD. The possible correlation between economic development and positiveness for EBV was also evaluated. For this purpose, data from 15 different geographic and economic areas were analysed using the Spearman coefficient. The development was evaluated according to the Human Development Rate. The results suggest a strong association between EBV and HD in Ceara State. It is more evident in the infant-juvenile group and in the subtype mixed cellularity. Besides, it shows an inverse relationship between regional development and positiviness into HD sample. Tipo: Dissertação

1998-01-01T00:00:00Z Farias, Livia Pontes http://repositorio.ufc.br/handle/riufc/85306 2026-03-24T13:03:00Z 2024-01-01T00:00:00Z

Título: Atividade antibacteriana e antibiofilme de óleorresinas extraídas de duas espécies de copaíba contra Staphylococcus aureus e avaliação da toxicidade Autor(es): Farias, Livia Pontes Abstract: Healthcare-associated infections (HAIs) affect patients under medical care during or after hospital admission, and are associated with numerous deaths annually, directly impacting global public health. This problem is exacerbated by the presence of strains exhibiting antimicrobial resistance, potentially leading to the ineffectiveness of antibiotic therapies. In this context, Staphylococcus aureus is a pathogen of great importance due to its frequent association with HAIs. The genus Copaifera, used in folk medicine due to its biological properties, stands out for its oleoresin production, with various pharmacological effects reported in the literature. Therefore, this study aimed to analyze the antimicrobial and antibiofilm activity of oleoresins extracted from C. arenicola (OCa) and C. langsdorffii (OCl) against S. aureus strains, as well as to evaluate their toxicity against cell lines (L929 and HaCaT) and Artemia salina. Regarding the results, both oleoresins showed Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values ​​between 125 and 500 μg/mL. For the non-volatile fractions of both species, the values ​​were 31.25 to 62.5 μg/mL for MIC and 31.25 to 125 μg/mL for MBC. For the major compounds, the concentrations ranged from 15.625 to 125 μg/mL for both MIC and MBC. The oleoresins also significantly inhibited biofilm formation, with reductions in viable cells ranging from 1 to 8.33 logs, a decline in biomass between 84.6 and 100%, and a decrease in metabolic activity between 67.80 and 100%. In pre-formed biofilms, reductions ranged from 0.71 to 2.71 logs of viable cells; decreases between 56.77% and 86.58% in total biomass; and from 17.77% to 92.62% in metabolic activity. Regarding Scanning Electron Microscopy, a reduction in cell quantity and extracellular matrix was observed, in addition to altered morphology after treatment with oleoresins in the CIM. In the cell viability assay, for both cell lines, the oleoresins showed cytotoxicity starting at a concentration of 250 μg/mL. Regarding A. salina, OCa showed a toxic effect starting at a concentration of 125 μg/mL, and OCl at 250 μg/mL. In light of the above, both oleoresins showed antibacterial and antibiofilm activity against the tested S. aureus strains, and most did not exhibit toxicity at concentrations lower than 250 μg/mL for the cell lines and A. salina. Thus, both oleoresins have promising potential against infections and biofilm formation associated with S. aureus Tipo: Dissertação

2024-01-01T00:00:00Z Oliveira, Leilson Carvalho de http://repositorio.ufc.br/handle/riufc/85049 2026-03-04T12:21:36Z 2026-01-01T00:00:00Z

Título: Avaliação in vitro da atividade antimicrobiana do Haloperidol em células planctônicas e biofilme de Candida spp. sensível e resistentes ao Fluconazol: determinação do possível mecanismo de ação Autor(es): Oliveira, Leilson Carvalho de Abstract: Fungal infections are particularly noteworthy due to their high morbidity and mortality rates. Estimates suggest that 1 billion individuals may have or live with some type of fungal infection, which is estimated to cause 3.8 to 4 million deaths annually. Candidiasis is the most prevalent opportunistic fungal infection worldwide, caused by yeasts of the genus Candida and exhibiting a high prevalence of clinical isolates resistant to conventional antifungals, making the development of new therapies paramount. In this context, drug repositioning is a strategy that aims to utilize medications already available on the market for purposes different from their initial use, for which haloperidol, a first-generation antipsychotic, has demonstrated potential in the antimicrobial field. From this perspective, the present study aims to evaluate the activity of haloperidol, alone and in combination with classic antifungals, against fluconazole-sensitive and fluconazole-resistant clinical strains of Candida spp., and the possible mechanisms associated with its antifungal action. Broth microdilution tests were performed to determine the Minimum Inhibitory Concentration (MIC), as indicated in the Clinical & Laboratory Standards Institute document M27-A3, for haloperidol and antifungals, along with checkerboard assays and the fractional inhibitory concentration index, flow cytometry, DNA damage assessment by comet assay, assays of formed and forming biofilms, and biofilm assessment by SEM. The results showed MICs of haloperidol ranging from 26.67 to 256 μg/mL. Regarding drug interaction assays, synergistic interactions were found between haloperidol and azoles, fluconazole and itraconazole, respectively, and 12.5% synergism with amphotericin B. The results also revealed that haloperidol induces apoptotic processes in C. albicans and C. auris species, causing DNA damage and methylation and inducing the expression of genes related to oxidative stress, contributing to homeostatic dysregulation, causing severe damage and inducing cell death. Biofilm assays showed a reduction in the viability of the formed biofilm in all species tested, ranging from 34.91% to 51.30% at the MIC concentration of the strains. Similar behavior was observed in the forming biofilm, where the reduction in viability ranged from 38.99% to 51.32%. Thus, haloperidol has great potential for antifungal action and stands out as a promising therapeutic alternative that needs further scientific investigation for future uses with anti-Candida action Tipo: Dissertação

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