http://repositorio.ufc.br/handle/riufc/397 2026-08-16T08:09:07Z http://repositorio.ufc.br/handle/riufc/87492 Título: Avaliação neurocognitiva de pessoas vivendo com HIV/AIDS em Fortaleza-CE Autor(es): Moura, Lucas Eliel Beserra Abstract: Chronic central nervous system (CNS) infection with HIV may be associated with HIV- associated neurocognitive disorder (HAND). This disorder has become more evident and concerning with the aging of the population living with HIV (PLHIV), as it has the potential to have an adverse functional impact, with impairment of various cognitive functions. The clinical diagnosis of HAND is based on various neuropsychological and functional tests. However, in many cases, the application of these tests may be impractical. The International HIV Dementia Scale (IHDS) is a simple, rapid, and validated screening test for the Brazilian population that can detect all forms of HAND. A cross-sectional study was conducted to estimate the frequency of HAND using the IHDS in conjunction with the Lawton Scale. Sixty-one patients were evaluated, with a prevalence of 63.93% of all forms of HAND and a correlation between this disorder and education (ρ = 0.656; p < 0.001), CD4 nadir (r = 0.28; p = 0.03), CD4 cell count (r = 0.29; p = 0.023), CD4/CD8 ratio (r = 0.552; p < 0.001), PHQ-9 (r = -0.446; p <0.001), GAD-7 (r = -0.354; p = 0.003), age (r = -0.761; p <0.001) and treatment time (r = -0.35; p = 0.006). After multivariate analysis, those with advanced age, lower education level and lower CD4/CD8 ratio independently presented worse IHDS values, showing themselves to be more susceptible to HAND and, therefore, should be screened for this condition. Tipo: Dissertação 2025-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/87456 Título: Impacto do exercício físico sobre as alterações hepáticas, bioquímicas, oxidativas, inflamatórias e metabólicas associadas a privação de sono em camundongos Swiss Autor(es): Nunes, Paulo Iury Gomes Abstract: Sleep deprivation (SD) is a stressor capable of inducing behavioral, neuroendocrine, inflammatory, and metabolic dysfunctions. Significant hepatic repercussions may occur secondary to SD. This study aimed to investigate whether chronic aerobic physical exercise can prevent or attenuate the deleterious effects induced by 72 hours of total sleep deprivation. We used male young adult Swiss mice, aged 90 to 150 days. Animals were allocated into four experimental groups: Control, Exercise (EXE), SD, and Exercise + SD (EXE+SD). The study included behavioral, biochemical, oxidative, hepatic histological, and metabolomic evaluations. Behavioral assessment revealed that SD increased immobility time in the forced swim test, reduced exploration in the Y-maze, and decreased entries into the open arms of the elevated plus maze, indicating impairments in memory, exploratory behavior, and anxiety-like states, respectively. Biochemical analyses demonstrated that SD increased serum levels of AST, ALT, urea, creatinine, triglycerides, and total cholesterol, along with significant reductions in albumin and glucose. These effects were accompanied by hepatic increases in TNF-α, IL-1β, IL-6, MCP-1, INF-γ, MDA, protein carbonylation, nitrite, and MPO activity, as well as reductions in GSH, SOD, and CAT. Histological analysis revealed mild diffuse inflammatory infiltration in the SD group. Hepatic metabolomics indicated that SD induced significant alterations in several metabolites, including reductions in dehydroascorbate, salicylate, fructose, and glucose. Physical exercise positively modulated the metabolic profile, restoring pathways related to amino acid, glyoxylate, glutathione, arginine, and proline metabolism. The EXE+SD group exhibited an intermediate profile, with partial or full reversal of SD- induced damage. These findings suggest that chronic aerobic physical exercise plays a protective role against the behavioral, inflammatory, redox, and metabolic hepatic alterations induced by sleep deprivation. Such findings have translational implications for the prevention of SD-associated metabolic disorders. Tipo: Tese 2025-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/87454 Título: Biperideno na prevenção de epilepsia em pacientes com traumatismo cranioencefálico em Sobral-Ceará: impacto do fluxo de atendimento na condução do ensaio clínico e na assistência aos pacientes do SUS Autor(es): Cristino, Eva Dias Abstract: Traumatic brain injury (TBI) constitutes a major public health problem in Brazil, with high incidence, morbidity and mortality, and significant socioeconomic impact. Among the sequelae of TBI are acute epileptic seizures and post-traumatic epilepsy. There are no effective therapies to prevent post-traumatic epilepsy. Biperiden, a muscarinic antagonist, has shown evidence of reducing and delaying seizures in animal models, and clinical trials in humans have demonstrated the drug’s safety, although its preventive efficacy has not yet been established. The development of TBI-targeted therapies depends on scientific evidence and adequate healthcare conditions that enable the conduct of clinical studies. This thesis aimed to identify and analyze aspects of the care pathway for patients with TBI in the Northern macro-region of Ceará that impacted both patient care and the conduct of a clinical trial, focusing on the study “Biperiden for the Prevention of Post-Traumatic Epilepsy.” This is an observational study with prospective data collection that evaluated 294 patients screened between September 2023 and December 2024 at Santa Casa de Misericórdia de Sobral, a trauma referral hospital in the interior of the state of Ceará. Patients diagnosed with skull and facial bone fractures, intracranial trauma, and/or crushing head injuries were included. Variables related to epidemiological profile, clinical severity, time intervals in care, and completeness of clinical records produced throughout the access pathway were analyzed. The results indicated a predominance of young male victims, mostly involved in motorcycle accidents. Essential information for clinical management and trial eligibility was frequently missing, such as time of trauma (28,2% of cases), time of admission to the first care unit (49,1%), and Glasgow Coma Scale (GCS) records at the scene (80,3%) and at the first care unit (27,1%). Sedated patients arrived more quickly at specialized services, suggesting prioritization of severe cases. Inconsistencies were also identified in the standardization of information transferred between services, possibly associated with structural limitations of the electronic systems used and the absence of well- defined institutional protocols. It was further observed that the time between trauma and arrival at the referral hospital correlated with geographic distance and severity of the condition, but may also have been influenced by regulatory barriers and communication failures. These factors directly affected participant inclusion in the clinical trial, especially due to the protocol requirement of administering the first dose of the intervention within 18 hours after trauma. Thus, although the regional access pathway for trauma patients is structured, deficiencies in the recording of critical information and delays in care compromised Santa Casa’s greater participation in the clinical trial, particularly due to the late arrival of patients outside the therapeutic window. These findings highlight the need for team training, documentation standardization, and the adoption of technological strategies that enhance interinstitutional communication, contributing not only to the feasibility of future multicenter studies but also to the improvement of healthcare delivery itself. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/87161 Título: Avaliação da atividade de produtos naturais otimizados em células planctônicas e biofilmes de Candida spp., Cryptococcus neoformans e Sporothrix spp Autor(es): Fernandes, Mirele Rodrigues Abstract: In recent decades, cases of severe fungal infections have increased, driven by the growing number of immunocompromised individuals, with reports of resistance and relapse becoming increasingly common. With only five existing classes of antifungals, the search for new drugs becomes urgent. In this sense, natural products have shown great potential. However, their low solubility, instability, and potential toxicity restrict their use. Optimization strategies, such as semisynthesis and microencapsulation, can be used in this regard. Considering this, this study aimed to evaluate the effects on planktonic cells and biofilms of natural products optimized by semisynthesis against Candida spp., Cryptococcus neoformans, and Sporothrix brasiliensis, and by microencapsulation of essential oils against Sporothrix spp. The study was conducted in two phases. The first evaluated the semisynthetic histone deacetylase inhibitors (iHDACs) N-hydroxy-8-(3-methoxyphenyl)octanamide (LDT536) and 8-(2-carbomethoxy)-N-hydroxy- 8-(3-methoxyphenyl)octanamide (LDT537) against Candida albicans, Candida tropicalis, C. neoformans, and S. brasiliensis through molecular docking, planktonic susceptibility, checkerboard assays with azoles, biofilm inhibition, cytotoxicity, and in vivo toxicity in Galleria mellonella. In the second phase, the in vitro planktonic susceptibility, drug interaction, and biofilm susceptibility of Sporothrix spp. to lemongrass and geranium essential oils encapsulated in chitosan microparticles were evaluated. In the in silico analyses, LDT536 and LDT537 demonstrated affinity for the catalytic sites of Class I fungal HDACs. In vitro, they inhibited the planktonic growth of the fungi, with MICs ranging from 32 to >64 µg/mL for LDT536 and from 8 to >64 µg/mL for LDT537, reducing the metabolic activity of C. albicans biofilms by more than 50% at a concentration of 4 µg/mL. In association with azole antifungals, they exhibited strong synergism against resistant strains of C. tropicalis, reducing the MIC of fluconazole by up to 256-fold. LDT536 demonstrated cytotoxicity at a concentration of 53.07 μg/mL, while LDT537 showed IC50 values of 9.42 μg/mL, with no deaths observed in G. mellonella larvae at a dose of 600 µg/mL. Meanwhile, the microparticles were able to inhibit in vitro planktonic cells and biofilms of Sporothrix spp. In the filamentous form of the fungus, empty microparticles (MQ) obtained the lowest MICs, between 0.25 and 2 µg/mL. In the yeast phase, MQGEO stood out with an MIC of 1 µg/mL for all evaluated strains. In combination with amphotericin B (AMB), MQCL and MQ demonstrated strong synergism against yeasts, reducing the MIC of AMB by up to 32 and 16 times, respectively. Against mature yeast biofilms, MQGEO reduced fungal metabolic activity starting at 32 µg/mL, presenting anSMIC50 of 161.27 µg/mL. Thus, it is concluded that both chemical-pharmaceutical semisynthesis and microencapsulation proved to be promising strategies in optimizing the antimicrobial activity of natural products, mainly in association with classical drugs, offering new perspectives for the management of invasive and refractory fungal infections. Tipo: Tese 2026-01-01T00:00:00Z