Samantha Souza Possa

Eosinophilic inflammation in allergic asthma.

Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL)-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR)3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modulation of immune response, induction of airway hyperresponsiveness and remodeling, characteristic features of asthma. Various types of promising treatments for reducing asthmatic response are related to reduction in eosinophil counts both in human and experimental models of pulmonary allergic inflammation, showing that the recruitment of these cells really plays an important role in the pathophysiology of allergic diseases such asthma.

Effects of Rho-kinase inhibition in lung tissue with chronic inflammation

We evaluated whether Rho-kinase inhibition (Y-27632) modulated distal lung responsiveness, inflammation, extracellular matrix remodeling and oxidative stress activation in guinea pigs (GPs) with chronic allergic inflammation. GPs were submitted to inhalation of ovalbumin (OVA-2×/week/4 weeks). From the 5th inhalation on, the Rho-kinase inhibitor group animals were submitted to Y-27632 inhalation 10min before each inhalation of OVA. Seventy-two hours after the seventh inhalation, the oscillatory mechanics of the distal lung strips were assessed under the baseline condition and after the ovalbumin challenge. Subsequently, the lung slices were submitted to morphometry. Rho-kinase inhibition in the ovalbumin-exposed animals attenuated distal lung elastance and resistance, eosinophils, IL-2, IL-4, IL-5, IL-13, TIMP-1, MMP-9, TGF-β, IFN-γ, NF-κB and iNOS-positive cells and the volume fraction of 8-iso-PGF2α, elastic, collagen and actin in alveolar walls compared with the OVA group (P<0.05). Rho-kinase inhibition contributed to the control of distal lung responsiveness, eosinophilic and Th1/Th2 responses and extracellular matrix remodeling in an animal model of chronic allergic inflammation.

New Pharmacological Targets for Asthma Drug Development

Asthma is an inflammatory disorder characterized by airway hyperresponsiveness, followed by inflammation, remodeling and oxidative stress in the respiratory system and lung tissue. While glucocorticosteroids remain the gold-standard of asthma therapy, they have limitations because of their potentially severe adverse effects and the presence of corticosteroid resistance in some patients. In the present review we will focus in four main groups of experimental pharmacological approaches for future asthma and hyperresponsiveness treatment: proteinase inhibitors and flavonoids, arginase and iNOS inhibition, Rho-kinase inhibitors, cholinergic anti-inflammatory system and nicotinic receptors.

Influence of Oral Tolerance on Lung Cytokines Expression and Oxidative Stress Activation in Guinea Pigs with Chronic Inflammation

Objective: We had previously demonstrated that oral induced tolerance attenuates lung tissue hyperresponsiveness, eosinophil inflammation and extracellular matrix remodelling in a model of chronic inflammation in guinea pigs. In the present study, we evaluated if these responses were associated to alterations on Th1/Th2 cell expression on airways and distal lung. Methods: Animals received seven inhalations of ovalbumin (1-5 mg/mL; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). After the last inhalation, lungs were removed for the histological analysis using morphometry. We assessed IL-2, IL-4, IL-13, IFN-γ and iNOS both in airways and distal lung. Results: There was an increase in IL-2, IL-4, IL-13, IFN-γ and iNOS positive cells both in airways and alveolar septa in ovalbumin-exposed guinea pigs compared with controls (P<0.05). Both in airways and in lung tissue there was a decrease in IL-4, IL-13 and iNOS positive cells in OT1 and OT2 compared to OVA (P<0.05). Considering IL-2 expression, there was an increase in OT1 and OT2 compared to OVA (P<0.05). We observed positive correlations among the functional responses and some inflammation and oxidative stress pathway activation markers evaluated, especially in alveolar wall. Conclusion: Oral tolerance induces a shift in Th1/Th2 and influences oxidative stress activation both in airways and distal lung of animals with chronic pulmonary allergic inflammation. These results may clarify the mechanisms involved in the attenuation of mechanical responsiveness, inflammation and remodelling of airways and distal lung by oral tolerance, as previously shown in this animal model.

Efficacy of telephone support as a tool for promoting daily physical activity in type 2 diabetic patients

Abstract Background: Type 2 diabetes mellitus (T2DM) is a highly prevalent public health problem. Although there is strong evidence supporting the essential role of physical activity in the management of T2DM, the