COPD Patients Exhibit Distinct Gene Expression, Accelerated Cellular Aging, and Bias to M2 Macrophages.

COPD, one of world's leading contributors to morbidity and mortality, is characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate, severe, and very severe. The molecular basis of inflammatory amplification, cellular aging, and immune response are critical to COPD pathogenesis. Our aim was to investigate EP300 (histone acetylase, HAT), HDAC 2 (histone deacetylase), HDAC3, and HDAC4 gene expression, telomere length, and differentiation ability to M1/M2 macrophages. For this investigation, 105 COPD patients, 42 smokers, and 73 non-smoker controls were evaluated. We identified a reduced HDAC2 expression in patients with mild, moderate, and severe severity; a reduced HDAC3 expression in patients with moderate and severe severity; an increased HDAC4 expression in patients with mild severity; and a reduced EP300 expression in patients with severe severity. Additionally, HDAC2 expression was reduced in patients with emphysema and exacerbator, along with a reduced HDAC3 expression in patients with emphysema. Surprisingly, smokers and all COPD patients showed telomere shortening. COPD patients showed a higher tendency toward M2 markers. Our data implicate genetic changes in COPD phenotypes and severity, in addition to M2 prevalence, that might influence future treatments and personalized therapies.

Nanodomains in cardiopulmonary disorders and the impact of air pollution.

Air pollution is a major environmental threat and each year about 7 million people reported to die as a result of air pollution. Consequently, exposure to air pollution is linked to increased morbidity and mortality world-wide. Diesel automotive engines are a major source of urban air pollution in the western societies encompassing particulate matter and diesel exhaust particles (DEP). Air pollution is envisioned as primary cause for cardiovascular dysfunction, such as ischemic heart disease, cardiac dysrhythmias, heart failure, cerebrovascular disease and stroke. Air pollution also causes lung dysfunction, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and specifically exacerbations of these diseases. DEP induces inflammation and reactive oxygen species production ultimately leading to mitochondrial dysfunction. DEP impair structural cell function and initiate the epithelial-to-mesenchymal transition, a process leading to dysfunction in endothelial as well as epithelial barrier, hamper tissue repair and eventually leading to fibrosis. Targeting cyclic adenosine monophosphate (cAMP) has been implicated to alleviate cardiopulmonary dysfunction, even more intriguingly cAMP seems to emerge as a potent regulator of mitochondrial metabolism. We propose that targeting of the mitochondrial cAMP nanodomain bear the therapeutic potential to diminish air pollutant - particularly DEP - induced decline in cardiopulmonary function.

Papain-induced experimental pulmonary emphysema in male and female mice.

In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 µL) or papain (10 U/50 µL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results.

Granuloma periférico de células gigantes imunohistoquímica ANTI-TNF-ALFA / Peripheral giant cell granuloma - Immunohistochemical study of tumor necrosis factor-alpha

O granuloma periférico de células gigantes (GPCG) é uma lesão localizada freqüentemente no periodonto, caracterizada pela presença de células gigantes multinucleadas, com morfologia semelhante à osteoclastos, que também exibem atividade fagocitária. O objetivo do presente estudo foi avaliar, em 24 lesões de GPCG, a expressão do TNF-α nas células gigantes, através de imunohistoquímica e morfometria. A expressão de TNF-α nas células gigantes foi estatisticamente significante maior nas lesões sem a presença de tecido ósseo, o que sugere uma possível ativação destas células para a fagocitose de hemossiderina e material hemorrágico. A expressão de TNF-α nas células gigantes das lesões que apresentaram osso trabecular reforça a hipótese de que estas células também possuam atividade osteoclástica.

Efeitos da hiperóxia sobre o pulmão de ratos Wistar / Effects of hyperoxia on Wistar rat lungs

OBJETIVO: Avaliar a repercussão da elevada concentração de oxigênio (hiperóxia) em um curto período de tempo no pulmão de ratos Wistar. MÉTODOS: Os animais foram divididos em grupos O10', O30', O90', ou seja, ratos expostos à hiperóxia por 10', 30' e 90', respectivamente, e no grupo controle (GC), exposto ao ar ambiente. Os animais foram sacrificados 24 h após a exposição. O lavado broncoalveolar foi realizado e os pulmões foram retirados para análise histológica e estereológica. RESULTADOS: Observamos um aumento do número de macrófagos (2169,9 ± 118,0, 1560,5 ± 107,0 e 1467,6 ± 39,0) e neutrófilos (396,3 ± 35,4, 338,4 ± 17,3 e 388,7 ± 11,7), concomitante a um aumento do dano oxidativo (143,0 ± 7,8 por cento, 180,4 ± 5,6 por cento e 235,0 ± 13,7 por cento) nos grupos O10', O30' e O90', respectivamente, quando comparados ao GC (781,3 ± 78,3 por cento, 61,6 ± 4,2 por cento e 100,6 ± 1,7 por cento). Na análise histológica e estereológica foram observados alvéolos e septos normais no GC (83,51 ± 1,20 por cento e 15 ± 1,21 por cento), no grupo O10' (81,32 ± 0,51 por cento e 16,64 ± 0,70 por cento) e no grupo O30' (78,75 ± 0,54 por cento e 17,73 ± 0,26 por cento). Entretanto, no grupo O90' foi notado um influxo de células inflamatórias nos alvéolos e nos septos alveolares. Hemácias extravasaram do capilar para o alvéolo (59,06 ± 1,22 por cento), com evidências de congestão, hemorragia e edema de septo (35,15 ± 0,69 por cento). CONCLUSÃO: Os resultados indicam que a hiperóxia induziu uma ação lesiva no grupo O90' sobre o parênquima pulmonar, com repercussões de dano oxidativo e infiltrado inflamatório.

OBJECTIVE: To study the effects of short-term exposure to high oxygen concentrations (hyperoxia) on Wistar rat lungs. METHODS: Animals were divided into three groups exposed to hyperoxia for 10', 30' and 90' (O10', O30', O90', respectively), together with a control group (exposed to room air). The animals were sacrificed 24 h after exposure. Bronchoalveolar lavage was performed, and the lungs were removed for histological and stereological analysis. RESULTS: In the O10', O30', and O90' groups, respectively and in comparison with the controls, we observed an increase in the numbers of macrophages (2169.9 ± 118.0, 1560.5 ± 107.0, and 1467.6 ± 39.0 vs. 781.3 ± 78.3) and neutrophils (396.3 ± 35.4, 338.4 ± 17.3, and 388.7 ± 11.7 vs. 61.6 ± 4.2), concomitant with an increase in oxidative damage (143.0 ± 7.8 percent, 180.4 ± 5.6 percent, and 235.0 ± 13.7 vs. 100.6 ± 1.7 percent). The histological and stereological analyses revealed normal alveoli and alveolar septa in the controls (83.51 ± 1.20 percent and 15 ± 1.21 percent), in the O10' group (81.32 ± 0.51 percent and 16.64 ± 0.70 percent), and in the O30' group (78.75 ± 0.54 percent and 17.73 ± 0.26 percent). However, in the O90' group, inflammatory cell infiltration was observed in the alveoli and alveolar septa. Red blood cells extravasated from capillaries to the alveoli (59.06 ± 1.22 percent), with evidence of congestion, hemorrhage, and septal edema (35.15 ± 0.69 percent). CONCLUSION: Hyperoxia for 90' caused injury of the lung parenchyma, resulting in oxidative damage and inflammatory cell infiltration.

[Effects of hyperoxia on Wistar rat lungs]. / Efeitos da hiperóxia sobre o pulmão de ratos Wistar.

OBJECTIVE: To study the effects of short-term exposure to high oxygen concentrations (hyperoxia) on Wistar rat lungs. METHODS: Animals were divided into three groups exposed to hyperoxia for 10', 30' and 90' (O10', O30', O90', respectively), together with a control group (exposed to room air). The animals were sacrificed 24 h after exposure. Bronchoalveolar lavage was performed, and the lungs were removed for histological and stereological analysis. RESULTS: In the O10', O30', and O90' groups, respectively and in comparison with the controls, we observed an increase in the numbers of macrophages (2169.9 +/- 118.0, 1560.5 +/- 107.0, and 1467.6 +/- 39.0 vs. 781.3 +/- 78.3) and neutrophils (396.3 +/- 35.4, 338.4 +/- 17.3, and 388.7 +/- 11.7 vs. 61.6 +/- 4.2), concomitant with an increase in oxidative damage (143.0 +/- 7.8%, 180.4 +/- 5.6%, and 235.0 +/- 13.7 vs. 100.6 +/- 1.7%). The histological and stereological analyses revealed normal alveoli and alveolar septa in the controls (83.51 +/- 1.20% and 15 +/- 1.21%), in the O10' group (81.32 +/- 0.51% and 16.64 +/- 0.70%), and in the O30' group (78.75 +/- 0.54% and 17.73 +/- 0.26%). However, in the O90' group, inflammatory cell infiltration was observed in the alveoli and alveolar septa. Red blood cells extravasated from capillaries to the alveoli (59.06 +/- 1.22%), with evidence of congestion, hemorrhage, and septal edema (35.15 +/- 0.69%). CONCLUSION: Hyperoxia for 90' caused injury of the lung parenchyma, resulting in oxidative damage and inflammatory cell infiltration.