http://repositorio.ufc.br/handle/riufc/46774 2026-08-16T13:05:43Z http://repositorio.ufc.br/handle/riufc/87499 Título: Análise dos efeitos do 2,6-diisopropilfenol (propofol) sobre a eletrofisiologia cardíaca dos pacientes com arritmias ventriculares mediadas por pós-potenciais tardios Autor(es): Távora, Ronaldo Vasconcelos Abstract: The 2,6-diisopropylphenol (propofol) is a well-established hypnotic agent widely used for anesthetic induction and maintenance. Recent investigations suggest a concentration-dependent modulating effect of this drug on the cardiac conduction system, demonstrating both proarrhythmic and antiarrhythmic properties. These phenomena are particularly relevant in automaticity-mediated arrhythmias, while exerting minimal influence on reentrant arrhythmias. The underlying pathophysiological mechanisms remain unclear, but evidence points to the involvement of sodium, calcium, and potassium ion channels, along with autonomic nervous system alterations. However, there are no published data regarding its interference in ventricular arrhythmias mediated by delayed afterdepolarizations (DADs), which represent one of the most common forms of ventricular arrhythmia. The assumption that intravenous propofol suppresses these arrhythmias often leads to a clinical preference for alternative hypnotic agents during electrophysiological studies aimed at catheter ablation. This practice relies mostly on anecdotal clinical reports and empirical observations lacking support in the literature. This study aimed to evaluate the effects of 2,6-diisopropylphenol on cardiac electrophysiological variables and its role in arrhythmias triggered by delayed afterdepolarizations. The study included 39 patients with no evidence of structural heart disease, presenting with symptomatic or high-burden ventricular outflow tract arrhythmias, who were eligible for catheter ablation. Diagnostic catheters were positioned in the coronary sinus, right ventricle, and the anteroseptal region of the tricuspid annulus to record atrial, ventricular, and His-bundle potentials. Under baseline conditions and during programmed atrial and ventricular stimulation, 15 electrophysiological parameters were recorded: heart rate, QRS duration, atrial conduction time, AH and HV intervals, ventriculoatrial (VA) conduction, anterograde and retrograde Wenckebach points, anterograde and retrograde atrioventricular node effective refractory periods, QT interval, atrial and ventricular effective refractory periods, coupling interval, and the number of premature ventricular contractions in 5 minutes (PVC5min). These evaluations were performed before and during intravenous propofol infusion, titrated to maintain a bispectral index (BIS) between 40 and 60. Results and data analysis suggests that propofol infusion exerts a primarily direct effect on the arrhythmic myocardial tissue, possibly through ion channel modulation. However, the drug's impact on ventricular ectopy density was markedly heterogeneous across the study sample. This variability could not be predicted by demographic data, electrocardiographic parameters, or the circadian behavior of the premature ventricular contractions. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86914 Título: Avaliação dos efeitos da minociclina em modelos experimentais de transtorno afetivo bipolar induzidos por anfetamina: avaliação de parâmetros comportamentais, neuroquímicos, computacionais e de viabilidade celular Autor(es): Oliveira, João Victor Souza Abstract: Bipolar disorder (BD) is a chronic psychiatric disorder characterized by alternating episodes of mania and depression. Its pathophysiology is multifactorial, involving alterations in monoaminergic neurotransmission, neuroinflammation, and oxidative stress. Despite the availability of mood stabilizers, the therapeutic limitations and adverse effects associated with current treatments highlight the need for novel pharmacological strategies. In this context, minocycline has attracted considerable interest due to its anti-inflammatory, antioxidant, and neuroprotective properties, as well as its high ability to cross the blood-brain barrier, making this antibiotic a promising adjuvant therapeutic agent for the treatment of BD. Therefore, the present study investigated the effects of oral minocycline (50 mg/kg) in experimental models of d-amphetamine-induced mania and amphetamine withdrawal-induced depression in Swiss mice using an integrated methodological approach comprising in vivo, in silico, and in vitro analyses. The effects of minocycline were compared with those of lithium (100 mg/kg) and valproic acid (300 mg/kg). Animals were subjected to the Open Field Test, Splash Test, and Forced Swim Test in both experimental models. In addition, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were determined in the prefrontal cortex, and oxidative stress markers were evaluated in the prefrontal cortex and hippocampus. In the mania model, repeated amphetamine administration induced hyperlocomotion and increased dopamine levels in the prefrontal cortex, confirming the induction of a manic-like phenotype. Under these conditions, minocycline reduced both the number of entries into and the time spent in the center zone of the open field and increased reduced glutathione (GSH) levels in the hippocampus, suggesting a neuroprotective effect associated with modulation of oxidative stress. In the amphetamine withdrawal-induced depression model, minocycline significantly increased the number of crossings and the frequency of rearing in the Open Field Test and reduced thiobarbituric acid reactive substances (TBARS) levels in the prefrontal cortex, indicating an antioxidant effect. No significant changes were observed in the Forced Swim Test. In silico analysis demonstrated that minocycline exhibited molecular affinity for JAK1 and JAK2 comparable to that of clinically used reference inhibitors, with binding energies of −7.2 kcal/mol and −9.1 kcal/mol, respectively, suggesting modulation of this signaling pathway as a potential mechanism underlying its neuroprotective effects. In vitro assays showed that both minocycline and valproate displayed a broad range of non-cytotoxic concentrations, whereas amphetamine significantly reduced PC12 cell viability at concentrations of 1000 μM and above. Furthermore, pretreatment with minocycline significantly increased the viability of amphetamine-exposed PC12 cells, demonstrating a protective effect against psychostimulant-induced cytotoxicity. A similar protective effect was also observed with valproic acid. Taken together, these findings demonstrate that minocycline attenuates behavioral, neurochemical, and oxidative alterations in amphetamine-induced experimental models of bipolar disorder and protects PC12 cells against amphetamine-induced cytotoxicity. These results reinforce the potential of minocycline as an adjuvant therapeutic strategy for bipolar disorder and suggest that modulation of signaling pathways involving JAK1 and JAK2 kinases may contribute to its neuroprotective effects. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/86404 Título: Efeitos neuroprotetores de nanoemulsões de canabidiol e tetrahidrocanabinol em modelos de epilepsia induzida por PTZ: implicações mitocondriais e astrogliais Autor(es): Girão Júnior, Francisco Josimar Abstract: Epilepsy is a prevalent neurological disorder in which mitochondrial dysfunction and glialactivation play a central role in its pathophysiology. The main phytocannabinoids of Cannabissativa, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), exhibit anticonvulsantproperties; however, their combined mechanisms of action, particularly regardingmitochondrial bioenergetics, oxidative stress, and astroglial modulation, remain poorlyelucidated. Therefore, this study investigated the effects of CBD and THC nanoemulsions,administered alone or in combination, in acute and chronic models of pentylenetetrazol(PTZ)-induced seizures. In the acute protocol, male Swiss mice received oral doses of CBD,THC, or their combinations in nanoemulsion form, and latency to the first generalized seizureand mortality were evaluated. In the chronic protocol, the development of epileptogenesis,cognitive performance, and neurochemical effects were assessed. Behavioral parameters in the chronic model included the novel object recognition test and the Y-maze test to analyzememory and cognitive function. Oxidative stress in the acute model was measured by lipidperoxidation markers (TBARS/MDA), nitrate/nitrite levels, and mitochondrial H₂O₂production. The expressions of GFAP, GAT-1, and Kir4.1 was evaluated by immunohistochemistry as markers of astrogliosis. Mitochondrial function was analyzed byoxygen consumption, respiratory control ratio, ADP/O ratio, and mitochondrial swelling in invitro and ex vivo preparations. The results demonstrated that the CBD/THC combinationsignificantly increased latency to seizures and death in the acute model, in addition to delaying the development of kindling in the chronic model. The nanoemulsions reduced oxidative and nitrosative stress levels and attenuated hippocampal astrogliosis. Significantmodulation of GAT-1 and Kir4.1 expression was observed in the treated groups, suggestingimproved synaptic homeostasis. In vitro and ex vivo assays showed enhanced mitochondrialbioenergetic efficiency. Overall, these findings indicate that the CBD/THC combination exertsa neuroprotective effect mediated by mitochondrial modulation, reduction of oxidative stress, and regulation of astroglial function, although dose-dependent cognitive effects and experimental limitations were observed. Tipo: Tese 2026-01-01T00:00:00Z http://repositorio.ufc.br/handle/riufc/85928 Título: Associações entre biomarcadores salivares inflamatórios e neurotróficos em crianças e adolescentes com Transtorno do Espectro Autista: estudo transversal em ambulatório de referência no Ceará Autor(es): Vianna, Marisa Perdigão de Negreiros Abstract: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition whose clinical complexity has driven the search for peripheral biomarkers capable of broadening the understanding of biological subgroups. In this context, saliva stands out as a promising matrix due to its non-invasive nature and good acceptability in pediatric populations. This study aimed to analyze the salivary profile of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and neurotrophins (BDNF and β-NGF) in children and adolescents with ASD treated at a specialized outpatient clinic, as well as to investigate the associations among these biomarkers and their relationship with clinical and contextual variables. This was a translational, observational, analytical, cross-sectional study conducted with 69 participants aged 2 to 17 years. Salivary biomarkers were measured using immunoenzymatic assays, and statistical analysis included the Shapiro-Wilk test and Spearman’s correlation coefficient. All biomarkers showed non-normal distribution. In the total sample, a strong positive correlation was observed between IL-6 and TNF-α (ρ = 0.85; p < 0.001), in addition to positive associations between both cytokines and β-NGF (ρ ≥ 0.71; p < 0.001), configuring a more stable relational axis between inflammation and neurotrophic signaling. In age-stratified analyses, this pattern remained present, with greater cohesion in Group 1 (2–4 years) and maintenance of the associations among IL-6, TNF-α, and β-NGF in Group 2 (5–9 years) and Group 3 (10–17 years), whereas IL-1β and BDNF showed more variable behavior across strata. Exploratory associations were also identified between biomarkers and clinical and contextual variables, notably the negative correlation between BMI and β-NGF in Group 1, the positive correlation between family income and BDNF across different age groups, and the negative associations between food selectivity and IL-6/TNF-α in Group 3. It is concluded that salivary biomarkers revealed a consistent pattern of association between inflammation and neurotrophy, especially involving the IL-6, TNF-α, and β-NGF axis, reinforcing saliva as a promising matrix for translational research in ASD. Tipo: Dissertação 2026-01-01T00:00:00Z