RESUMO
Neural respiratory drive (NRD) is measured using a non-invasive recording of respiratory electromyographic signal. The parasternal intercostal muscle can assess the imbalance between the load and capacity of respiratory muscles and presents a similar pattern to diaphragmatic activity. We aimed to analyze the neural respiratory drive in seventeen individuals with hypertension during quite breathing and maximal voluntary ventilation (MVV) (103.9 ± 5.89 vs. 122.6 ± 5 l/min) in comparison with seventeen healthy subjects (46.5 ± 2.5 vs. 46.4 ± 2.4 years), respectively. The study protocol was composed of quite breathing during five minutes, maximum inspiratory pressure followed by maximal ventilatory ventilation (MVV) was recorded once for 15 seconds. Anthropometric measurements were collected, weight, height, waist, hip, and calf circumferences, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), BMI, and conicity index (CI). Differences between groups were analyzed using the unpaired t-test or Mann-Whitney test to determine the difference between groups and moments. A significance level of 5% (p<0,05) was adopted for all statistical analyses. The group of individuals with hypertension presented higher values when compared to the healthy group for neural respiratory drive (EMGpara% 17.9±1.3 vs. 13.1±0.8, p = 0.0006) and neural respiratory drive index (NRDi (AU) 320±25 vs. 205.7±15,p = 0.0004) during quiet breathing and maximal ventilatory ventilation (EMGpara% 29.3±2.7 vs. 18.3±0.8, p = 0.000, NRDi (AU) 3140±259.4 vs. 1886±73.1,p<0.0001), respectively. In conclusion, individuals with hypertension presented higher NRD during quiet breathing and maximal ventilatory ventilation when compared to healthy individuals.
Assuntos
Hipertensão , Humanos , Pessoa de Meia-Idade , Hipertensão/fisiopatologia , Masculino , Feminino , Estudos de Casos e Controles , Adulto , Eletromiografia , Ventilação Voluntária Máxima/fisiologia , Respiração , Músculos Respiratórios/fisiopatologiaRESUMO
Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2-/-) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2-/- mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2-/- mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing ß cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.
Assuntos
Proteínas de Ligação a DNA/uso terapêutico , Diabetes Mellitus Experimental/genética , Imunidade Inata/genética , Animais , Homeostase , Humanos , Interleucina-18/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The ruthenium complex, trans-[Ru(Bz)(NH 3) 4SO 2](CF 3SO 3) 2 1, Bz = benznidazole ( N-benzyl-2-(2-nitro-1 H-imidazol-1-yl)acetamide), is more hydrosoluble and more active (IC 50try/1 h = 79 +/- 3 microM) than free benznidazole 2 (IC 50try/1 h > 1 mM). 1 also exhibits low acute toxicity in vitro (IC 50macrophages > 1 mM) and in vivo (400 micromol/kg < LD 50 < 600 micromol/kg) and the formation of hydroxylamine is more favorable in 1 than in 2 by 9.6 kcal/mol. In murine acute models of Chagas' disease, 1 was more active than 2 even when only one dose was administrated. Moreover, 1 at a thousand-fold smaller concentration than the considered optimal dose for 2 (385 micromol/kg/day = 100 mg/kg/day), proved to be sufficient to protect all infected mice, eliminating the amastigotes in their hearts and skeletal muscles as observed in H&E micrographics.