ABSTRACT
Mechanical ventilation (MV) is a lifesaving therapy for patients with acute or chronic respiratory failure. Despite, it can also cause lung injury by inducing or worsening inflammatory responses and oxidative stress. Several clinical approaches have protective effects on the lungs, including the prone position and exogenous surfactant; however, few studies have evaluated the association between the two strategies, especially in individuals without previous lung injury. We tested the hypothesis that the effects of the homogenization in lung aeration caused by the prone position in association with the anti-inflammatory properties of exogenous surfactant pre-treatment could have a cumulative protective effect against ventilator-induced lung injury. Therefore, Wistar rats were divided into four experimental groups: Mechanical Ventilation in Supine Position (MVSP), Mechanical Ventilation in Prone position (MVPP), Mechanical Ventilation in Supine Position + surfactant (MVSPS), and Mechanical Ventilation in Prone Position + Surfactant (MVPPS). The intranasal instillation of a porcine surfactant (Curosurf®) was performed in the animals of MVSPS and MVPPS 1 h before the MV, all the rats were subjected to MV for 1 h. The prone position in association with surfactant decreased mRNA expression levels of pro-inflammatory cytokines in ventilated animals compared to the supine position; in addition, the NfκB was lower in MVPP, MVSPS and MVPPS when compared to MVSP. However, it had no effects on oxidative stress caused by MV. Pre-treatment with exogenous surfactant was more efficient in promoting lung protection than the prone position, as it also reduced oxidative damage in the lung parenchyma. Nevertheless, the surfactant did not cause additional improvements in most parameters that were also improved by the prone position. Our results indicate that the pre-treatment with exogenous surfactant, regardless of the position adopted in mechanical ventilation, preserves the original lung histoarchitecture, reduces redox imbalance, and reduces acute inflammatory responses caused by mechanical ventilation in healthy adult Wistar rats.
ABSTRACT
In recent years, several advances have been observed in vaccinology especially for neglected tropical diseases (NTDs). One of the tools employed is epitope prediction by immunoinformatic approaches that reduce the time and cost to develop a vaccine. In this scenario, immunoinformatics is being more often used to develop vaccines for NTDs, in particular visceral leishmaniasis (VL) which is proven not to have an effective vaccine yet. Based on that, in a previous study, two predicted T-cell multi-epitope chimera vaccines were experimentally validated in BALB/c mice to evaluate the immunogenicity, central and effector memory and protection against VL. Considering the results obtained in the mouse model, we assessed the immune response of these chimeras inMesocricetus auratushamster, which displays, experimentally, similar pathological status to human and dog VL disease. Our findings indicate that both chimeras lead to a dominant Th1 response profile, inducing a strong cellular response by increasing the production of IFN-γ and TNF-α cytokines associated with a decrease in IL-10. Also, the chimeras reduced the spleen parasite load and the weight a correlation between protector immunological mechanisms and consistent reduction of the parasitic load was observed. Our results demonstrate that both chimeras were immunogenic and corroborate with findings in the mouse model. Therefore, we reinforce the use of the hamster as a pre-clinical model in vaccination trials for canine and human VL and the importance of immunoinformatic to identify epitopes to design vaccines for this important neglected disease.