https://tedebc.ufma.br/jspui/handle/tede/544 2026-09-15T22:38:46Z https://tedebc.ufma.br/jspui/handle/tede/7209 Título: Avaliação da atividade antimicrobiana da desferrioxamina in sílico e in vitro contra Mycobacterium abscessus subsp. massiliense Autor: LIRA , Roseane Lustosa de Santana Primeiro orientador: SOUSA, Eduardo Martins de Abstract: Infections caused by Mycobacterium abscessus subsp. massiliense (Mabs) pose a growing public health threat, particularly for immunocompromised individuals. Consequently, novel therapeutic strategies are urgently needed to combat bacterial resistance and dismantle biofilm structures. Desferrioxamine (DFO), an iron chelator commonly used in the treatment of iron overload, has shown antimicrobial potential due to its ability to limit iron availability, an essential element for microbial survival. This study aimed to evaluate the antimicrobial activity of desferrioxamine in silico and in vitro against Mabs. In silico analyses were performed to predict pharmacological activity (PASS online), oral availability and pharmacokinetics (SwissADME and PROTOX), toxicity (WaytoDrug), and to characterize the molecular interactions of desferrioxamine with specific enzymatic targets. For the in vitro analysis, molecular assays (PCR), antimicrobial activity assessments, and biofilm formation investigations against Mabs were conducted. The results demonstrate that in silico evaluation (PASS Online) predicted a high probability of iron antagonism by DFO (Pa = 0.911), suggesting potential inhibition of bacterial growth. Predictive pharmacokinetic analysis (SwissADME) indicated high plasma protein binding (>90%) and low intestinal absorption of DFO, factors that may restrict its systemic bioavailability. Moderate toxicity was observed, with mutagenic and nephrotoxic effects. Molecular docking revealed promising interactions of DFO with essential Mabs proteins, suggesting an inhibitory effect. In in vitro assays with RAW 264.7 cells, DFO showed no significant cytotoxicity. DFO significantly inhibited nitric oxide production by M. abscessus-infected RAW 264.7 macrophages. The minimum inhibitory concentration results for DFO reinforce its therapeutic potential and warrant further investigation into its antimicrobial activity. DFO demonstrates a dose-dependent effect on cytokine expression regulation; at low concentrations (0.5 x MIC), DFO reduces pro inflammatory cytokines TNF-α, IL-1β and IL-6. Given these findings, it is concluded that DFO has potential as an adjuvant antimicrobial agent against Mycobacterium abscessus subsp. massiliense, particularly due to its ability to sequester iron and compromise bacterial survival. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese 2026-05-22T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/7133 Título: Avaliação do efeito analgésico e anti inflamatório do ambroxol em modelo experimental de osteoartrite em rato Autor: MESQUITA, Michelline Joana Tenório Albuquerque Madruga Primeiro orientador: GARCIA, João Batista Santos Abstract: Ambroxol is a mucolytic agent widely used in the treatment of respiratory diseases; however, Ambroxol is a mucolytic agent widely used in the treatment of respiratory diseases. However, evidence from the literature has demonstrated its anti-inflammatory, analgesic, and immunomodulatory properties, suggesting its potential for drug repurposing. In this context, this thesis integrated a systematic review and an experimental study to investigate the mechanisms of action and therapeutic effects of ambroxol in experimental models of non pulmonary diseases, with an emphasis on osteoarthritis (OA). Initially, a systematic review was conducted, registered in the Open Science Framework (OSF), following the PICO strategy and PRISMA guidelines, with searches performed in the PubMed/MEDLINE, Embase, and Scopus databases. Of the 353 studies identified, eight met the eligibility criteria. The review demonstrated that ambroxol exerts anti-inflammatory, antioxidant, and antinociceptive effects in different non-pulmonary experimental models by reducing pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), increasing the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione), decreasing oxidative stress, improving histopathological changes, and attenuating pain through mechanisms related, among others, to the blockade of voltage-gated sodium channels, thereby reinforcing its potential for drug repurposing. Subsequently, an experimental study was conducted to evaluate the antinociceptive and anti inflammatory effects of ambroxol in an experimental model of osteoarthritis. Adult male Wistar rats underwent OA induction on day zero (D0) by intra-articular injection of monosodium iodoacetate (MIA) and were allocated into the following groups: Healthy, Negative Control (CTRL−), Meloxicam (2 mg/kg), and Ambroxol (10, 50, and 100 mg/kg). Treatments were administered orally by gavage once daily for 28 days. Behavioral assessments included the Rotarod test, Gait Analysis, Weight Bearing test, Von Frey test, and Rat Grimace Scale, in addition to radiographic and histopathological evaluations and quantification of pro- and anti inflammatory cytokines (IL-1β, IL-6, and IL-10). Ambroxol treatment significantly improved nociceptive parameters and motor function, while reducing radiographic and histopathological scores, showing performance comparable to meloxicam in several outcomes. Marked reductions in IL-1β and IL-6 levels were observed, whereas IL-10 levels were lower in the ambroxol-treated groups, suggesting an earlier resolution of the inflammatory response. Taken together, the findings from the systematic review and the experimental study demonstrate that ambroxol exhibits consistent anti-inflammatory, antioxidant, and antinociceptive properties, in addition to attenuating structural joint damage associated with osteoarthritis. These findings reinforce the potential of ambroxol as a candidate for drug repurposing in osteoarthritis. Further studies are required to better elucidate its mechanisms of action, establish the optimal dosage regimen and treatment duration, and support the translation of these findings into clinical studies. Instituição: Universidade Federal do Maranhão Tipo do documento: Tese 2026-07-08T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/7118 Título: PACIENTES RENAIS CRÔNICOS ATENDIDOS NA FARMÁCIA ESTADUAL DE MEDICAMENTOS ESPECIALIZADOS NO MUNÍCIPIO DE SÃO LUÍS, MARANHÃO: Perfil clínico-epidemiológico, estudo etnofarmacológico e estratégias para Farmacovigilância Autor: MUNIZ, Raoni Sousa Primeiro orientador: AMARAL, Flavia Maria Mendonça do Abstract: Chronic Kidney Disease (CKD) is a syndrome characterized by progressive changes in renal structure and function, presenting high morbidity and mortality and a significant socioeconomic impact. Due to its complex clinical progression, the disease requires continuous care and prolonged use of medications to ensure access to therapies that control the progression of the pathology and reduce complications, making the Specialized Component of Pharmaceutical Assistance essential in Brazil. However, the traditional use of medicinal plants and barriers to accessing health services encourage self-medication with herbal preparations, which can represent serious risks to patients with CKD due to possible adverse events. Given this scenario, this study aimed to describe the epidemiological profile and pattern of use of plants for medicinal purposes among patients with CKD, evaluating potential risks of drug interactions with specialized treatment and proposing measures to minimize dangers in this population. The methodology consisted of an observational, cross-sectional, and analytical study with 280 patients registered in the Horus system and assisted by the State Pharmacy of Specialized Medicines in São Luís, Maranhão, Brazil. Data were collected through interviews using a structured questionnaire, and medical records were used to confirm the disease; multivariate logistic regression analysis was applied to identify factors associated with the use of plants for medicinal purposes. The results revealed a sample with a slight male predominance (50.71%) and a higher concentration in the 51-60 age group (22.86%). The socioeconomic profile showed low educational attainment, with 70.00% of patients having completed high school, and marked financial vulnerability, with 93.57% living on less than two minimum wages. Regarding the diagnosis of CKD, 51.79% discovered the disease in routine examinations, although 18.21% had a family history, mainly first-degree relatives (34%). The practice of polypharmacy is evident, with 78.57% of respondents using additional medications, primarily for the control of metabolic disorders and hypertension. Approximately 15% of patients use plants for medicinal purposes, with the most frequent species being: lemon balm (Lippia alba (Mill.) N.E. Br., 5.36%), lemongrass (Cymbopogon citratus (DC.) Stapf, 3.57%), chamomile (Matricaria recutita L., 2.14%), boldo (Plectranthus barbatus Andrews, 1.79%), and mango leaf (Mangifera indica L, 1.07%). Thus, the clinical risk is aggravated by polypharmacy and/or the use of species with nephrotoxic potential. It is concluded that the implementation of pharmacovigilance actions and the qualification of healthcare professionals are imperative measures to mitigate risks and promote the rational use of therapeutic resources in this population. Instituição: Universidade Federal do Maranhão Tipo do documento: Dissertação 2026-03-27T00:00:00Z https://tedebc.ufma.br/jspui/handle/tede/7093 Título: EFEITOS DO AMBIENTE ISOLADO, CONFINADO, EXTREMO SOBRE OS ESTADOS DE HUMOR NA ESTAÇÃO ANTÁRTICA COMANDANTE FERRAZ Autor: GOMES, Jayne Pimenta Primeiro orientador: MENDES, Thiago Teixeira Abstract: Introduction: Antarctica represents one of the most challenging scenarios for human presence, characterized as an isolated, confined, and extreme (ICE) environment, in which factors such as geographic isolation, restricted mobility, environmental monotony, and intense seasonal variations act simultaneously. In this context, mood emerges as a variable sensitive to the interaction between psychobiological and environmental factors, being widely used as an indicator of adaptation in extreme conditions. Objective: To analyze the effects of the ICE environment on the mood states of military personnel at the Comandante Ferraz Antarctic Station (EACF). Methodology: Sixteen military personnel participated in the study, monitored over 11 months in 2020, with six data collection phases (January to November). The Brunel Mood Scale (BRUMS) questionnaire was applied, and anthropometric measurements were taken. The data were analyzed using IBM SPSS Statistics 23.0, adopting descriptive statistics (mean and standard deviation or median and interquartile range, according to the data distribution). Normality was verified by the Shapiro–Wilk test, and differences between periods were assessed by the Friedman test, with a significance level of p ≤ 0.05. Results: There were no statistically significant differences in mood dimensions verified by the Friedman, TMD, and Effect Size indices over the analyzed period (p > 0.05), suggesting a pattern of positive mood in the ICE environment. Conclusion: The findings suggest that exposure to the isolated, confined, and extreme (ICE) environment of Antarctica did not promote statistically significant changes in mood dimensions over time, indicating stability of positive mood during the analyzed period. Instituição: Universidade Federal do Maranhão Tipo do documento: Dissertação 2026-04-30T00:00:00Z