When pneumonia becomes a double congenital diaphragmatic hernia

When pneumonia becomes a double congenital diaphragmatic hernia

Lower NPAS3 expression during the later stages of abnormal lung development in rat congenital diaphragmatic hernia

Purpose Congenital diaphragmatic hernia (CDH) is characterized by a developmental defect in the diaphragm, pulmonary hypoplasia and pulmonary hypertension. NPAS3 is a PAS domain transcription factor regulating Drosophila tracheogenesis. NPAS3 null mice develop pulmonary hypoplasia in utero and die after birth due to respiratory failure. We aimed to evaluate NPAS3 expres- sion during normal and abnormal lung development due to CDH. Methods CDH was induced by administering 100 mg/ml nitrofen to time-pregnant dams on embryonic day (E) 9 of gestation. Lungs were isolated on E15, E18 and E21 and NPAS3 localization was determined by immunohisto- chemistry and quantified using Western blotting. Results We found that only E21 hypoplastic CDH lungs have reduced expression of NPAS3 in the terminal sac- cules. Western blotting confirmed the down-regulation of NPAS3 protein in the nitrofen-induced hypoplastic lungs. Conclusions We demonstrate for the first time that ni- trofen-induced hypoplastic CDH lungs have reduced NPAS3 expression in the terminal saccules during the later stages of abnormal lung development. Our findings suggest that NPAS3 is associated with pulmonary hypoplasia in CDH.

Epigastric pain: incarceration or rotation?

Introduction: Acute intrathoracic gastric volvulus occurs when the stomach has a twist mesenteroaxial/organoaxial or chest cavity resulting in a dilatation or rupture of the diaphragmatic hiatus or diaphragmatic hernia. The purpose of this work is to show a interesting case of gastric volvulus in a patient with several comorbidities. Case Report: A 77-year-old female with past history of hiatal hernia and mental disease associated with diabetes and atrial fibrillation. Patient went to the emergency department due to vomiting associated with blood. Analytical parameters (WBC, HGB, PCR, metabolic panel and liver function), showed no significant alterations. Thoracic X-ray revealed an enlarged mediastinum due to herniation of the stomach. A computed tomography (CT) scan confirmed intrathoracic localization of the gastric antrum with twist. Patient’s symptoms were relieved by nasogastric intubation and analgesia. After six months, the patient is still asymptomatic. Conclusion: In general, the treatment of an acute gastric volvulus requires an emergent surgical repair. In patients who are not surgical candidates (with comorbidities or an inability to tolerate anesthesia), endoscopic reduction should be attempted. Chronic gastric volvulus may be treated non-emergently, and surgical treatment is increasingly being performed using a laparoscopic approach. In this case, it is a chronic form that was solved with the placement of the nasogastric tube. A nasogastric decompression is an option in the chronic form of hiatal hernia associated to gastric volvulus in patients with serious comorbidities.

Looking for mechanisms regulating lung growth in CDH: rat and human studies

Tese de Doutoramento em Ciências da Saúde

Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development

Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. In vitro analyses were performed on Sprague-Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) α, β and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up-regulation of RARα and RARγ.