The aim of this study is to test the hypothesis that the early changes in lung mechanics and the amount of type III collagen fiber do not predict the evolution of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury (ALI). For this purpose, we analyzed the time course of lung parenchyma remodeling in murine models of pulmonary and extrapulmonary ALI with similar degrees of mechanical compromise at the early phase of ALI. Lung histology (light and electron microscopy), the amount of elastic and collagen fibers in the alveolar septa, the expression of matrix metalloproteinase-9, and mechanical parameters (lung-resistive and viscoelastic pressures, and static elastance) were analyzed 24 h, 1, 3, and 8 wk after the induction of lung injury. In control (C) pulmonary (p) and extrapulmonary (exp) groups, saline was intratracheally (it; 0.05 ml) instilled and intraperitoneally (ip; 0.5 ml) injected, respectively. In ALIp and ALIexp groups, mice received Escherichia coli lipopolysaccharide (10 microg it and 125 microg ip, respectively). At 24 h, all mechanical and morphometrical parameters, as well as type III collagen fiber content, increased similarly in ALIp and ALIexp groups. In ALIexp, all mechanical and histological data returned to control values at 1 wk. However, in ALIp, static elastance returned to control values at 3 wk, whereas resistive and viscoelastic pressures, as well as type III collagen fibers and elastin, remained elevated until week 8. ALIp showed higher expression of matrix metalloproteinase-9 than ALIexp. In conclusion, insult in pulmonary epithelium yielded fibroelastogenesis, whereas mice with ALI induced by endothelial lesion developed only fibrosis that was repaired early in the course of lung injury. Furthermore, early functional and morphological changes did not predict lung parenchyma remodeling.

AimTo evaluate the effects of alcohol and nicotine, when used alone or simultaneously, in the development of apical periodontitis induced in rats, using a correlative analytic approach with micro‐CT, histological and immunohistochemical analysis.MethodologyTwenty‐eight male Wistar rats were arranged into four groups: Control, Nicotine, Alcohol and Alcohol + Nicotine. The alcohol groups were exposed to self‐administration of a 25% alcohol solution, whilst the other groups drunk only filtered water. The nicotine groups received daily intraperitoneal injections of a solution with 0.19 μL of nicotine per mL, whilst the other groups received saline solution. The pulps of the left mandibular first molars were exposed for 28 days to induce periapical lesions. Throughout the experiment, drug administration was maintained, and the animals had their weight and solid and liquid consumption measured. After euthanasia, the mandibles were removed and the area, volume and major diameter of the periapical lesions were measured using micro‐computed tomography images. The samples were submitted to histopathological evaluation and immunohistochemistry for RANKL and PTHrP. Statistical analysis was undertaken with a significance level of 5%. Nonparametric data were analysed using the Kruskal–Wallis test followed by Dunn's test, whilst one‐way anova followed by Tukey's test was performed for parametric data.ResultsThe alcohol groups had lower solid and liquid consumption and gained less weight when compared to the nonalcohol groups (P < 0.05). The Alcohol + Nicotine group had lesions with significantly larger volume and area when compared to the other groups (P < 0.05), whilst the Alcohol or Nicotine groups had significantly larger lesions than the control group (P < 0.05). There was no significant difference in the largest diameter of the lesions amongst groups (P > 0.05). The experimental groups had greater inflammatory response scores than the control group (P < 0.05), and the representative samples had more pronounced immunoreaction against RANKL and PTHrP antibodies.ConclusionsAlcohol and nicotine consumption exacerbated the inflammatory response and the development of periradicular lesions in rats. The association of both substances enhanced their harmful effects.