Objective: To investigate the effects of quercetin in a model of bleomycin-induced pulmonary inflammation and fibrosis. Methods: Seventynine adult male hamsters were randomized to receive intratracheal (IT) instillations and intraperitoneal (IP) injections in four configurations: IP vehicle/IT saline (VS group, n = 16); IP quercetin/IT saline (QS group, n = 16); IP vehicle/IT bleomycin (VB group, n = 27); and IP quercetin/ IT bleomycin (QB group, n = 20). Quercetin and bleomycin were administered at 30 mg/kg/day and 10 U/kg, respectively. Quercetin was started/discontinued 3 days before/14 days after the IT instillations. Results: The mortality rate was significantly higher in the VB group than in the other groups (44% vs. VS: 0%; QS: 0%; and QB: 15%). Lung levels of thiobarbituric acid reactive substances (× 10−2 nmol/mg) were significantly higher in the VB group (6.6 ± 1.3 vs. VS: 5.5 ± 0.8; QS: 2.5 ± 0.6; and QB: 5.8 ± 0.6). Lung levels of reduced glutathione (× 10−2 nmol/mg) were significantly lower in the VB/QB groups than in the VS/QS groups (28.9 ± 13.8/28.6 ± 14.8 vs. 43.9 ± 16.0/51.1 ± 20.3), whereas those of hydroxyproline (mg/g) were significantly higher (201.6 ± 37.3/177.6 ± 20.3 vs. 109.6 ± 26.1/117.5 ± 32.0).Mean lung septal thickness (μm) was greatest in the VB group (16.9 ± 3.2 vs. VS: 3.0 ± 0.3; QS: 3.3 ± 0.2; and QB: 5.2 ± 1.1). Conclusions: In a hamster model of lung injury, quercetin exhibited anti-inflammatory effects that are related, at least in part, to its antioxidant properties.

Keywords: Pulmonary fibrosis; Bleomycin; Flavonoids; Lipid peroxidation.

Objective: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an experimental model of pulmonary fibrosis. Methods: A total of 120 male C57BL/6 mice were distributed into four groups: SS, injected with saline (placebo) and then receiving intratracheal (IT) instillation of saline; SB, injected with saline (placebo) and then receiving IT instillation of bleomycin; PB, treated with plasmid only, without bacterial genome, and then receiving IT instillation of bleomycin; and BB, treated with the vaccine and then receiving IT instillation of bleomycin. Bleomycin was instilled 15 days after the last immunization, and the animals were killed six weeks thereafter. The left and right lungs were removed, the former for morphological analysis and the latter for hydroxyproline measurements. Results: The proportion of deaths within the first 48 h after the IT instillation (deaths attributed to the surgical procedure) was higher in the SB group than in the SS group (57.7% vs. 11.1%). The mean area of pulmonary interstitial septa was greater in the SB and PB groups (53.1 ± 8.6% and 53.6 ± 9.3%, respectively) than in the SS and BB groups (32.9 ± 2.7% and 34.3 ± 6.1%, respectively). The mean area of interstitial septa stained by picrosirius was greater in the SB, PB and BB groups than in the SS group (8.2 ± 4.9%, 7.2 ± 4.2% and 6.6 ± 4.1%, respectively, vs. 2.0 ± 1.4%). The total hydroxyproline content in the lung was significantly lower in the SS group (104.9 ± 20.9 pg/lung) than in the other groups (SB: 160.4 ± 47.8 pg/lung; PB: 170.0 ± 72.0 pg/lung; and BB: 162.5 ± 39.7 pg/lung). Conclusions: Immunization with the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of bleomycin-induced lung lesion.

Keywords: Pulmonary fibrosis; Bleomycin; Collagen.

Objetivo: Investigar os efeitos agudos da administração endovenosa de extrato da fumaça do cigarro (EFC) em parâmetros funcionais respiratórios, inflamatórios e histológicos em ratos e comparar esse potencial modelo de lesão pulmonar aguda (LPA) com aquele com o uso de ácido oleico (AO). Métodos: Foram estudados 72 ratos Wistar machos divididos em quatro grupos: tratados somente com soro fisiológico (SF; grupo controle); tratados com EFC e SF (grupo EFC); tratados com SF e AO (grupo AO); e tratados com EFC e AO (grupo EFC/AO). Resultados: As médias de complacência foram significantemente menores nos grupos AO e EFC/AO (2,12 ± 1,13 mL/cmH2O e 1,82 ± 0,77 mL/cmH2O, respectivamente) do que no controle (3,67 ± 1,38 mL/cmH2O). A proporção de neutrófilos e a atividade das metaloproteinases 2 e 9 em lavado broncoalveolar foram significantemente maiores nos grupos AO e EFC/AO que no controle. O acometimento pulmonar avaliado por morfometria foi significantemente maior nos grupos AO e EFC/AO (72,9 ± 13,8% e 77,6 ± 18,0%, respectivamente) do que nos grupos controle e EFC (8,7 ± 4,1% e 32,7 ± 13,1%, respectivamente), e esse acometimento foi significantemente maior no grupo EFC que no grupo controle. Conclusões: A administração endovenosa de EFC, nas doses e tempos deste estudo, associou-se à LPA mínima. O EFC não potencializou a LPA induzida por AO. Estudos adicionais são necessários para esclarecer o papel potencial desse modelo como método de estudo dos mecanismos de agressão pulmonar pelo tabaco.

Keywords: Tabagismo; Lesão pulmonar aguda; Modelos animais.

Objective: Neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease characterized by tachypnea, retractions, crackles, and hypoxia. The aim of this study was to report and discuss the clinical, imaging, and histopathological findings in a series of NEHI cases at a tertiary pediatric hospital, with an emphasis on diagnostic criteria and clinical outcomes. Methods: Between 2003 and 2011, 12 full-term infants were diagnosed with NEHI, based on clinical and tomographic findings. Those infants were followed for 1-91 months. Four infants were biopsied, and the histopathological specimens were stained with bombesin antibody. Results: In this case series, symptoms appeared at birth in 6 infants and by 3 months of age in the remaining 6. In all of the cases, NEHI was associated with acute respiratory infection. The most common initial chest HRCT findings were ground-glass opacities that were in the middle lobe/lingula in 12 patients and in other medullary areas in 10. Air trapping was the second most common finding, being observed in 7 patients. Follow-up HRCT scans (performed in 10 patients) revealed normal results in 1 patient and improvement in 9. The biopsy findings were nonspecific, and the staining was positive for bombesin in all samples. Confirmation of NEHI was primarily based on clinical and tomographic findings. Symptoms improved during the follow-up period (mean, 41 months). A clinical cure was achieved in 4 patients. Conclusions: In this sample of patients, the diagnosis of NEHI was made on the basis of the clinical and tomographic findings, independent of the lung biopsy results. Most of the patients showed clinical improvement and persistent tomographic changes during the follow-up period, regardless of the initial severity of the disease or type of treatment.

Keywords: Lung diseases, interstitial/diagnosis; Lung diseases, interstitial/treatment; Tomography, X-ray computed.