http://repositorio.ufc.br/handle/riufc/399 Wed, 15 Apr 2026 18:43:40 GMT 2026-04-15T18:43:40Z http://repositorio.ufc.br/handle/riufc/85848 Título: Vigilância em saúde única da resistência a antifúngicos e a compostos de amônio quaternário em Candida spp. no Ceará e busca por alternativa terapêutica Autor(es): Brasil, Jaiane Alves Abstract: From a One Health perspective, tackling antifungal resistance in Candida spp. requires an understanding of multiple factors, such as interaction with environments and chemical agents. Furthermore, drug repositioning and combination therapy are strategies to overcome therapeutic failures. This study aimed to isolate and identify Candida spp. from human clinical samples (n=59), hospital surfaces (n=25), production animals (n=107), and the environment of these animals (n=9); analyze the sensitivity profile to the antifungals FLC, MCF, and AMB; and the effect of benzalkonium chloride (BZ) and didecyl dimethyl ammonium chloride (DDAC) against isolates in planktonic and biofilm forms, as well as evaluate the effect of deferiprone (DEF), an iron chelator, on Candida spp. in planktonic and biofilm forms, isolated and in combination with the antifungals fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS). Finally, it was evaluated whether the inhibition of the fungus by DFP was reversed with ferrous sulfate (FeSO₄). Sensitivity to antifungals, quaternary ammonium compounds, and deferiprone was analyzed according to document m27-a3. The checkerboard method was used to evaluate the interaction between deferiprone and the antifungals. The antibiofilm activity of the antifungals, ammonium compounds, and deferiprone was evaluated by MTT reduction and biomass quantification by crystal violet. 109 Candida spp. yeasts were isolated. FLC showed variable MIC, from 0.125 to 64 µg/ml for isolates of human origin; 0.5 to 4 µg/ml for isolates from hospital environments; 0.125 to 64 µg/ml for isolates of animal origin, and 1 to 32 µg/ml for isolates from animal environments. MICs for MCF ranged from 0.0625 to 0.5 µg/ml for isolates of human origin; 0.0625 to 1 µg/ml for isolates from hospital environments; 0.0625 to 0.1 µg/ml for isolates of animal origin, and 0.03 µg/ml for isolates from animal environments. AMB exhibited MICs of 0.031 to 1 µg/ml for isolates of human origin; 0.125 to 0.5 µg/ml for isolates from hospital environments; 0.031 to 1 µg/ml for isolates of animal origin, and 0.06 and 0.25 µg/ml for isolates from animal environments. DDA showed MICs between 0.0625 and 1 µg/mL, and BZ showed MICs ranging from 0.0625–4 µg/mL. Forming and mature Candida spp. biofilms showed a significant reduction in metabolic activity and biomass after exposure to BZ and DDA. DEF showed MICs ranging from 16 to 1024 µg/mL against the tested isolates. In the checkerboard assay, DEF reduced the MICs of FLC, AMB, and CAS by up to 8, 32, and 64 times, respectively, against the planktonic form. In the MTT assay, DEF caused an increase in the metabolic activity of forming biofilms of C. tropicalis and C. glabrata; and a tendency towards reduced metabolic activity of mature Candida spp. biofilms (n=12) at 1024 µg/mL. Crystal violet analysis revealed an increase in the biomass of forming C. parapsilosis biofilms when treated with DEF; and a tendency towards a reduction in mature Candida spp. biofilms (n=12) at concentrations of 256 to 1024 µg/mL and 2 to 32 µg/mL, when compared to drug-free controls. Supplementation with (FeSO₄) reduced the antifungal efficacy of DEF against planktonic Candida spp. DEF demonstrated antifungal activity and synergism with FLC, AMB, and CAS against Candida spp., with greater efficacy observed against C. glabrata. Furthermore, DEF significantly influenced biofilm formation, showing a species-dependent effect. However, its effectiveness was significantly reduced by supplementation with FeSO₄, demonstrating that it acts directly on iron balance for Candida spp. Tipo: Tese Thu, 01 Jan 2026 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/85848 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/85535 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 Wed, 01 Jan 2025 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/85535 2025-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/85424 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 Thu, 01 Jan 1998 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/85424 1998-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/85306 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 Mon, 01 Jan 2024 00:00:00 GMT http://repositorio.ufc.br/handle/riufc/85306 2024-01-01T00:00:00Z