Ronaldo Aparecido da Silva

Aerobic training reverses airway inflammation and remodelling in an asthma murine model

Aerobic training (AT) decreases dyspnoea and exercise-induced bronchospasm, and improves aerobic capacity and quality of life; however, the mechanisms for such benefits remain poorly understood. The aim of the present study was to evaluate the AT effects in a chronic model of allergic lung inflammation in mice after the establishment of airway inflammation and remodelling. Mice were divided into the control group, AT group, ovalbumin (OVA) group or OVA+AT group and exposed to saline or OVA. AT was started on day 28 for 60 min five times per week for 4 weeks. Respiratory mechanics, specific immunoglobulin (Ig)E and IgG1, collagen and elastic fibres deposition, smooth muscle thickness, epithelial mucus, and peribronchial density of eosinophils, CD3+ and CD4+, IL-4, IL-5, IL-13, interferon-γ, IL-2, IL-1ra, IL-10, nuclear factor (NF)-κB and Foxp3 were evaluated. The OVA group showed an increase in IgE and IgG1, eosinophils, CD3+, CD4+, IL-4, IL-5, IL-13, NF-κB, collagen and elastic, mucus synthesis, smooth muscle thickness and lung tissue resistance and elastance. The OVA+AT group demonstrated an increase of IgE and IgG1, and reduction of eosinophils, CD3+, CD4+, IL-4, IL-5, IL-13, NF-κB, airway remodelling, mucus synthesis, smooth muscle thickness and tissue resistance and elastance compared with the OVA group (p<0.05). The OVA+AT group also showed an increase in IL-10 and IL-1ra (p<0.05), independently of Foxp3. AT reversed airway inflammation and remodelling and T-helper cell 2 response, and improved respiratory mechanics. These results seem to occur due to an increase in the expression of IL-10 and IL-1ra and a decrease of NF-κB.

Exercise deactivates leukocytes in asthma.

Leukocytes play a central role in asthma physiopathology. Aerobic training (AT) reduces leukocytes recruitment to the airways, but the effects of AT on some aspects of leukocytes activation in asthma are unknown. Therefore, the effects of 4 weeks of AT on airway inflammation, pulmonary and systemic Th2 cytokines levels, leukocytes expression of pro and anti-inflammatory, pro-fibrotic, oxidants and anti-oxidants mediators in an experimental model of asthma was investigated. AT reduced the levels of IL-4, IL-5, IL-13 in bronchoalveolar lavage fluid (BALF) (p<0.001), serum levels of IL-5, while increased BALF and serum levels of IL-10 (p<0.001). In addition, AT reduced leukocytes activation, showed through decreased expression of Th2 cytokines (IL-4, IL-5, IL-13; p<0.001), chemokines (CCL5, CCL10; p<0.001), adhesion molecules (VCAM-1, ICAM-1; p<0.05), reactive oxygen and nitrogen species (GP91phox and 3-nitrotyrosine; p<0.001), inducible nitric oxide synthase (iNOS; p<0.001), nuclear factor kB (NF-kB; p<0.001) while increased the expression of anti-inflammatory cytokine (IL-10; p<0.001). AT also decreased the expression of growth factors (TGF-beta, IGF-1, VEGF and EGFr; p<0.001). We conclude that AT reduces the activation of peribronchial leukocytes in a mouse model of allergic asthma, resulting in decreased airway inflammation and Th2 response.

Macro- and microstructural organization of the rabbit's celiac-mesenteric ganglion complex (Oryctolagus cuniculus)

The macro- and microstructures of the rabbit celiac-mesenteric ganglion complex are described in 20 young animals. We found ten celiac ganglia, twenty-seven cranial mesenteric ganglia and eleven celiac-mesenteric ganglia. The celiac ganglia had a rectangular shape in nine cases (90%) and a circular one in one case (10%). The cranial mesenteric ganglia presented triangular (66.7%), rectangular (11.1%), L-shape (18.5%) and semi-lunar (3.7%) arrangements. The celiac-mesenteric ganglia were organized in three patterns: a single left celiac-mesenteric ganglion having a caudal portion (72.7%); celiac-mesenteric ganglia without a caudal portion (18.2%) and a single celiac-mesenteric ganglion with two portions: left and right (9.1%). The microstructure was investigated in nine celiac-mesenteric ganglia. The results showed that the celiac-mesenteric ganglion is actually a ganglion complex constituted of an agglomerate of ganglionic units separated by nerve fibers, capillaries and septa of connective tissue. Using the semi-thin section method we described the cellular organization of the celiac-mesenteric ganglion complex. Inside of each ganglionic unit, there were various cell types: principal ganglion neurons (PGN), glial cells (satellite cells) and SIF cells (small intensely fluorescent cells or small granular cells), which are the cytologic basis for each ganglionic unit of the rabbits celiac-mesenteric ganglion complex.

Anxiety and depression are related to dyspnea and clinical control but not with thoracoabdominal mechanics in patients with COPD.

OBJECTIVE To investigate the relationship between the presence of symptoms of anxiety or depression with breathing pattern and thoracoabdominal mechanics at rest and during exercise in COPD. METHODS Cross-sectional study enrolled 54 patients with COPD ranked according to Hospital Anxiety and Depression Scale (HAD) score and compared to dyspnea, clinical control, hypercapnia, breathing pattern and thoracoabdominal mechanics at rest and during exercise. RESULTS Seventeen patients with COPD had no symptoms, 12 had anxiety symptoms, 13 had depressive symptoms and 12 had both symptoms. COPD with depressive symptoms presented greater degree of dyspnea (p<0.01). Poor clinical control was observed in COPD with anxious and/or depressive symptoms (p<0.05). Breathing pattern and thoracoabdominal mechanics were similar among all groups at rest and during exercise. CONCLUSIONS COPD with symptoms of depression report more dyspnea. Anxiety and depression are associated with poor clinical control without impact on breathing pattern and thoracoabdominal mechanics in COPD.

Association between Maximal Aerobic Capacity and Psychosocial Factors in Adults With Moderate-to-Severe Asthma

Background. The symptoms of asthma impair health-related quality of life (HRQoL), increase anxiety and depression and may keep subjects from engaging in physical exercise. Physical inactivity has been related to poor asthma outcomes; however, the association between physical fitness and psychosocial disorders remains poorly understood. Objective. To verify the association between aerobic capacity, HRQoL, and psychological distress in adults with moderate or severe persistent asthma who were clinically stable. Methods. Eighty-eight participants (68 females) with either moderate or severe persistent asthma (age range, 20–60 years) who were under medical treatment for at least 6 months and considered clinically stable were studied. Participants were evaluated on two non-consecutive days. On the first day, the HRQoL, depression and anxiety levels and pulmonary function were assessed. On the second day, subjects underwent cardiopulmonary exercise testing. Results. Using the agglomerative cluster approach, two clusters were identified: 21 participants (24%) were grouped in Cluster 1, and 67 (76%) were grouped in Cluster 2. Asthmatic subjects from Cluster 1 exhibited increased aerobic capacity, better HRQoL and lower depression levels than did subjects in Cluster 2 (p < .05). No difference was observed between the clusters with respect to gender, age, body mass index (BMI) or pulmonary function (p > .05). The discriminant function model exhibits good accuracy (R2 = 0.79) and predicted 93% of the case allocations. Conclusion. Our results suggest an association between reduced exercise capacity, low HRQoL and increases in depressive symptoms in clinically stable asthmatic subjects. These results suggest the need to assess physical fitness and psychosocial distress during asthma treatment and the importance of a multidisciplinary approach.

Exercise reverses OVA-induced inhibition of glucocorticoid receptor and increases anti-inflammatory cytokines in asthma

The purpose of this study was to determine the effect of aerobic exercise training (AT) on the expression of glucocorticoid receptors (GR) and anti‐inflammatory cytokines in an asthma model. BALB/c mice were divided into groups control (CT; nonsensitized/nontrained), aerobic training (AT; nonsensitized/trained), ovalbumin (OVA; sensitized/not trained), and OVA+AT (sensitized/trained). OVA groups received OVA by inhalation, and the AT groups completed 1, 3, or 7 days of exercise (60 min/session). Expression of GR, IL‐4, IL‐5, IL‐10, IL‐1ra, NF‐κB, TGF‐β, VEGF, ICAM‐1, VCAM‐1; eosinophils counting; and airway remodeling (AR) features [airway smooth muscle (ASM) and epithelial thickness and collagen fiber deposition] were quantified. OVA sensitization induced a decrease in the expression of GR and increases in the eosinophil, IL‐4, IL‐5, NF‐κB, TGF‐β, VEGF, ICAM‐1, VCAM‐1, and AR features (P < 0.05). After 3 days, AT reversed the OVA‐induced reduction in the expression of GR, and subsequently induced increases in the expression of IL‐10 and IL‐1ra (seventh day). In contrast, the eosinophil migration, the expression of NF‐κB, IL‐4, IL‐5, TGF‐β, RANTES, VEGF, ICAM‐1, VCAM‐1, and the AR features (P < 0.05) were reduced. AT increases the expression of GR and anti‐inflammatory cytokines (IL‐10 and IL‐1ra) and reduces the expression of inflammatory mediators and airway inflammation in an animal model of asthma.

Airway remodeling is reversed by aerobic training in a murine model of chronic asthma

The aim of this study was to investigate if the aerobic training (AT) reverses airway remodeling (AR) in an asthma model. BALB/c were divided into four groups: control (unsensitized and untrained); ovalbumin (OVA: sensitized and untrained); AT (unsensitized and trained) and OVA + AT. Allergic inflammation was induced with intraperitoneal and OVA inhalation. AT (low intensity; 5×/week; 60 min/session) was performed at 7, 15, and 30 days. Leukocyte counting in the bronchoalveolar lavage fluid; the expression of IL‐5, eotaxin, RANTES, intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1); AR features (airway smooth muscle, epithelium thickness, collagen and elastic fibers, mucus production); and AR inducers (transforming growing factor‐beta, osteopontin, vascular endothelial growth factor). OVA induced an increase in leukocyte airway migration and increased AR features (P < 0.05). After 7 days, AT reversed the OVA‐induced eosinophil and macrophage airway migration, the expression of IL‐5, eotaxin, RANTES, ICAM‐1, VCAM‐1, and all AR inducers. However, total reversion of the AR features and inducers and airway inflammation occurred only after 15 days of AT compared with the OVA groups (P < 0.05) and the effects were maintained until the 30th day. AT reverses AR after 15 days and this effect is preceded by the inhibition of leukocyte migration and occurs simultaneously with the reduction in the expression of inflammatory mediators and AR inducers.

Comparison of the Effects of Aerobic Conditioning Before and After Pulmonary Allergic Inflammation

The aim of this study is to compare the effects of aerobic conditioning (AC) before (ACBS) and after (ACAS) allergic sensitization. BALB/c mice were divided into two main groups: ACBS and ACAS. Each groups was divided into subgroups: control (nonsensitized/nontrained), AC (nonsensitized/trained), ovalbumin (OVA) (sensitized/nontrained), AC + OVA (trained/sensitized), and OVA + AC (sensitized/trained). Sensitization was induced using OVA and AC performed in treadmill (moderate intensity). We examined IgE and IgG1 levels, eosinophil counting, expression of Th1 (interleukin (IL)-2, IFN-α) and Th2 cytokines (IL-4, IL-5, IL-13), IL-10, vascular endothelial growth factor (VEGF), and airway remodeling. IgE and IgG1 were decreased only when exercise was performed before sensitization (ACBS); however, there was a decrease of eosinophils, Th2 cytokines, VEGF, and airway remodeling and increase in IL-10 in either ACBS or ACAS groups. Our results demonstrate that aerobic conditioning reduces Th2 response before and after sensitization by increasing IL-10 while the production of anaphylactic antibodies is reduced only when exercise is performed before sensitization.

Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice

Work-exacerbated asthma (WEA) is defined as preexisting asthma that worsens with exposure to irritants [e.g., chlorine (Cl2) derivatives] in the workplace. The maximum allowable concentration in the workplace of Cl2 exposure is 3 mg/ m3 (described in OSHA). We investigated in an experimental asthma model in mice the effects of a single exposure to a sodium hypochlorite dose with this allowed chlorine concentration and a tenfold higher dose. Acute chlorine exposure at 3.3 mg/m3 in the OVA-sensitized group increased eosinophils in the peribronquial infiltrate, cytokine production, nasal mucus production and the number of iNOS positive cells in the distal lung compared to only sensitized mice. The exposure to a higher dose of 33.3 mg/m3 in the OVA-sensitized group resulted in an increase in respiratory system elastance, in the total and differential numbers of inflammatory cells in bronchoalveolar lavage fluid, IL-4, IL-5, and IL-17 in the lungs, eosinophils in peribronquial infiltrate and mucus content in nasal compared to non-exposed and sensitized animals. In this asthma model, chorine exposures at an allowable dose, contributed to the potentiation of Th2 responses. The functional alterations were associated with increased iNOS and ROCK-2 activation in the distal lung.