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Caracterização clínica, comportamental, sensorial e eletrofisiológica de crianças e adolescentes com dor reumatológica crônica: estudo transversal comparativo

2026-09-10T13:21:00Z

Título: Caracterização clínica, comportamental, sensorial e eletrofisiológica de crianças e adolescentes com dor reumatológica crônica: estudo transversal comparativo Autor(es): Silva, Tauane Grasiela dos Santos Abstract: Rheumatic conditions comprise a diverse group of diseases that predominantly affect the joints, but also muscles, bones, connective tissues, and internal organs, arising from immune-mediated, inflammatory, infectious, or degenerative mechanisms, characterized by a prolonged, painful, and function-limiting course, and which also affect children and adolescents. Among pediatric rheumatic conditions, juvenile idiopathic arthritis (JIA), of inflammatory and autoimmune nature, and juvenile fibromyalgia syndrome (JFS), of non-inflammatory nature and associated with central sensitization mechanisms, potentially involving cognitive, autonomic, and sensory dysfunction, stand out. In this context, electroencephalography (EEG) stands out as a tool for objectively characterizing the neurological processes underlying pediatric chronic pain. However, studies detailing the physiological mechanisms involved in JFS and JIA remain scarce. Objective: To characterize the clinical, behavioral, sensory, and electrophysiological profile of children and adolescents with chronic rheumatic pain resulting from juvenile fibromyalgia syndrome or juvenile idiopathic arthritis, compared with a healthy control group matched by sex and age range. Materials and Methods: This was an analytical, observational, cross-sectional study including children and adolescents of both sexes, aged 7 to 18 years, allocated into two groups: a pain group (JFS and JIA) and a control group. The groups were assessed using socioeconomic questionnaires, pain intensity (11-point numerical rating scale), mechanical detection threshold (esthesiometry), electrophysiological profile (electroencephalogram), and cognitive profile (auditory P300 event-related potential). Results: The sample consisted of 54 participants, 27 in the pain group and 27 in the control group, stratified into children and adolescents (24 children and 30 adolescents). A mean diagnostic delay of 21.3 months was observed in children and 50.7 months in adolescents. Children in the pain group showed generalized mechanical hypersensitivity to light touch at a site distant from the affected joint (p=0.004; d=−1.297), and adolescents in the pain group showed greater pain sensitivity to mechanical pressure (p=0.013 and p=0.045) and greater self-reported pain intensity (p=0.001) compared with controls. No intergroup EEG differences were identified under the resting-state condition. During the P300 paradigm, adolescents in the pain group showed greater relative amplitude in the theta band and lower relative amplitude in the beta3 band in the right anterior and posterior regions compared with controls (p<0.05; d ranging from 0.94 to 1.41), a finding significant under the uncorrected primary criterion adopted in this exploratory study; in a Benjamini-Hochberg sensitivity analysis restricted to relative-amplitude variables and applied per age subgroup within each experimental condition (m=24), right posterior theta power remained significant (q=0.015). In children, a differentiated pattern of right posterior relative amplitude was observed during exposure to educational and recreational screen conditions. The topographic pain contrast between diagnoses was statistically significant for back pain, leg pain, and headache, all more frequent in JFS (FDR-adjusted p<0.01). Conclusion: In response to the overall objective, the electrophysiological profile of children and adolescents with JFS and JIA, compared with healthy controls, was characterized by the absence of EEG differences at rest and by specific alterations under active cognitive and sensory demand. Children and adolescents with JFS and JIA present measurable sensory alterations and specific electrophysiological changes during conditions of active cognitive and sensory demand, though not generalized to the resting state, consistent with early stages of central sensitization and pain-related cognitive interference. These findings reinforce the relevance of early diagnosis as a possible therapeutic window and point to the need for longitudinal studies investigating the progression of these alterations throughout development.

Sensibilidade β-adrenérgica e variabilidade alterada da frequência cardíaca no hipotireoidismo: uma abordagem mecanicista

2026-09-04T15:24:37Z

Título: Sensibilidade β-adrenérgica e variabilidade alterada da frequência cardíaca no hipotireoidismo: uma abordagem mecanicista Autor(es): Rocha, Camila Souza Gama Abstract: Hypothyroidism is one of the most prevalent endocrine disorders worldwide, affecting more than 10% of adults, and is associated with structural and functional alterations of the cardiovascular system. Although its chronotropic and hemodynamic effects are well described, the mechanisms integrating autonomic modulation and β-adrenergic sensitivity in the genesis of cardiac electrical alterations are poorly understood. This study aimed to investigate changes in cardiac electrical function resulting from autonomic modulation associated with hypothyroidism in a murine model. Methods: Male Swiss mice were used (n = 6–7 per group; 5–6 weeks old; 25–30 g). Hypothyroidism was induced with methimazole (0.1% in drinking water) for 21 days, while the control group received water only. Cardiac function was assessed by in vivo electrocardiography on days 0, 11, and 21, determining heart rate, electrical conduction, and heart rate variability in the time and frequency domains. β-adrenergic sensitivity was analyzed through intraperitoneal administration of isoproterenol, dobutamine, and salbutamol, with electrocardiographic monitoring before and 3 minutes after administration. Adenylyl cyclase activity was assessed in isolated hearts perfused using a Langendorff system, before and after stimulation with forskolin. The expression of β₁ and β₂ receptors, protein kinase A (PKA), and phospholamban (PLB) was determined by Western blot. Results: Hypothyroid animals showed a significant reduction in heart rate, prolongation of the PR interval, and an increase in corrected QT. Heart rate variability revealed an increase in the Very Low Frequency (VLF) component, an increase in the Root mean square of successive differences (RMSSD), and a reduction in the Standard deviation of NN intervals (SDNN), characterizing autonomic imbalance with vagal predominance and decreased overall adaptability. Hypothyroid hearts showed a significant reduction in β₁-receptor expression and PKA substrate phosphorylation, as well as an increase in β₂-receptor expression. These results indicate that hypothyroidism reduces canonical β₁-adrenergic/PKA signaling while increasing β₂-adrenergic receptor expression. The chronotropic response to isoproterenol and dobutamine was attenuated, accompanied by reduced PKA substrate phosphorylation, indicating decreased cardiac β₁-adrenergic responsiveness. In contrast, the response to salbutamol was increased, with no changes in PKA substrate phosphorylation or PLB expression/phosphorylation, suggesting that β₁-adrenergic signaling is selectively impaired in hypothyroidism, with a possible reorganization toward the β₂-adrenergic signaling pathway. Forskolin stimulation restored the heart rate response without altering the p-PLB/PLB ratio, which remained unchanged, indicating preservation of the intracellular steps downstream of β-adrenergic receptor activation. Conclusion: Hypothyroidism induces marked remodeling of cardiac adrenergic signaling, with a greater contribution of alternative pathways associated with the β₂ adrenergic receptor. These findings demonstrate that thyroid hormone deficiency leads to reorganization of cardiac adrenergic signaling, contributing to bradycardia, reduced chronotropic adaptability, and decreased complexity of autonomic control in hypothyroidism.

Efeito anti-inflamatório e antioxidante da Solanum stipulaceum Willd. ex Roem. & Schult na inflamação cutânea em camundongos

2026-08-28T19:00:48Z

Título: Efeito anti-inflamatório e antioxidante da Solanum stipulaceum Willd. ex Roem. & Schult na inflamação cutânea em camundongos Autor(es): Nunes, Etjo Rodrigo Santana Abstract: Solanum stipulaceum, popularly known as "sacatinga", is a plant endemic to the Brazilian Caatinga, traditionally used for gastric disorders. Scientific evidence supports its gastroprotective effects, attributed to bioactive compounds with antioxidant and antiinflammatory properties, and confirms the presence of phenolic acids and flavonoids, reinforcing the relevance of investigating its anti-inflammatory potential. This study aimed to evaluate the anti-inflammatory and antioxidant effects of the hydroethanolic extract of Solanum stipulaceum leaves (EHSs) and of 4-hydroxybenzoic acid in a mouse model of skin inflammation. Female Swiss mice were subjected to inflammation induction in the right ear by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA; 1 μg/ear in 20 μL acetone). Five minutes later, the animals received topical treatment with EHSs and AHB at different doses (0.3, 1.0, and 3.0 mg/ear), vehicle (acetone), or dexamethasone (0.05 mg/ear) as a positive control. The contralateral ears received only vehicle and served as paired controls. Six hours after inflammation induction, the animals were euthanized, and ear tissues were collected using an 8 mm punch for evaluation of edema (mass difference between ears), macroscopic analysis, histological analysis (dermo-epidermal thickness), myeloperoxidase (MPO) activity, cytokine quantification, total hydroperoxides, and catalase (CAT) activity. Compared to the vehicle + TPA group, topical treatment with EHSs (0.3, 1.0, and 3.0 mg/ear) and AHB (3.0 mg/ear) promoted significant reduction of edema (p < 0.0001 for EHSs; p = 0.0382 for AHB), of macroscopic inflammatory parameters (corroborated by histological findings), of dermoepidermal thickness (p = 0.0002; p = 0.0018; p = 0.0054, respectively), and of MPO activity (EHSs: EHSs: p < 0.0001; < 0.0001; p = 0.0003, respectively; AHB: p = 0.0145). At the dose of 3 mg/ear, EHSs also reduced IL-1β and IL-6 concentrations (both p < 0.0001), as did AHB (p = 0.013 and p = 0.0061, respectively), when compared to the vehicle + TPA group. Regarding oxidative stress parameters, treatment with EHSs decreased total hydroperoxides (p = 0.0062) and increased catalase activity (p = 0.0205). These findings demonstrate the anti-inflammatory and antioxidant properties of EHSs, with partial contribution of 4-hydroxybenzoic acid (AHB), reinforcing the pharmacological potential of this species as a candidate for the development of therapeutic strategies for inflammatory and oxidative skin disorders.

Limiar glicêmico durante teste muscular inspiratório incremental em indivíduos saudáveis e com doença pulmonar obstrutiva crônica

2026-08-12T19:11:48Z

Título: Limiar glicêmico durante teste muscular inspiratório incremental em indivíduos saudáveis e com doença pulmonar obstrutiva crônica Autor(es): Silva, Wasly Santana Abstract: Introduction: The glycemic threshold (GT) during the incremental inspiratory muscle test (IIMT) has been proposed by our research group as a tool for inspiratory muscle functional assessment and individualized inspiratory muscle training (IMT) prescription. However, its agreement with the first lactate threshold (LT1) and its applicability in individuals with chronic obstructive pulmonary disease (COPD) have not yet been investigated. Objectives: To evaluate the agreement between GT and LT1 during the IIMT in healthy individuals and to investigate the determination of GT in individuals with COPD, as well as its associations with clinical and functional variables. Methods: Two studies were conducted using the IIMT. In the first study, healthy individuals performed the IIMT with simultaneous determination of GT, LT1, and the second lactate threshold (LT2). In the second study, individuals with COPD performed the IIMT for GT determination and analysis of its association with rating of perceived exertion, dyspnea, functional capacity, and cardiovascular autonomic balance. The incremental protocol started at 10% of the S-Index, with progressive workload increments until the point of exhaustion (PE). Results: In the first study, GT showed good agreement with LT1. LT1 and GT occurred at 22±8.3% and 26±13.2% of the S-Index, respectively, whereas LT2 and PE were identified at 44±10.1% and 60±14.1% of the S-Index. Bland–Altman analysis demonstrated low bias between methods for relative workload (−3.84±10.44% of the S-Index) and no proportional bias (p=0.06; R²=0.25). In the second study, GT was identified at 25±11.6% of the S-Index and showed a strong correlation with rating of perceived exertion during the IIMT (r=0.84; p<0.01). In addition, PE and ΔGT–PE were correlated with cardiovascular autonomic balance (LF/HF: r=−0.83 and r=−0.71; p<0.01), whereas ΔGT–PE was also correlated with dyspnea assessed by the modified Medical Research Council (mMRC) scale (r=−0.68; p=0.01) and Borg dyspnea at the end of the six-minute walk test (r=−0.83; p<0.01). Conclusion: GT is an identifiable physiological marker during the IIMT, showing agreement with LT1 in healthy individuals and association with important clinical and functional variables in individuals with COPD. These findings support its potential as a tool for inspiratory muscle functional assessment and individualized IMT prescription.