Impaired Autophagic Activity Contributes to the Pathogenesis of Bronchopulmonary Dysplasia. Evidence from Murine and Baboon Models.

Bronchopulmonary dysplasia (BPD) is a common and serious complication associated with preterm birth. The pathogenesis of BPD is incompletely understood, and there is an unmet clinical need for effective treatments. The role of autophagy as a potential cytoprotective mechanism in BPD remains to be fully elucidated. In the present study, we investigated the role and regulation of autophagy in experimental models of BPD. Regulation and cellular distribution of autophagic activity during postnatal lung development and in neonatal hyperoxia-induced lung injury (nHILI) were assessed in the autophagy reporter transgenic GFP-LC3 (GFP-microtubule-associated protein 1A/1B-light chain 3) mouse model. Autophagic activity and its regulation were also examined in a baboon model of BPD. The role of autophagy in nHILI was determined by assessing lung morphometry, injury, and inflammation in autophagy-deficient Beclin 1 heterozygous knockout mice (Becn1+/-). Autophagic activity was induced during alveolarization in control murine lungs and localized primarily to alveolar type II cells and macrophages. Hyperoxia exposure of neonatal murine lungs and BPD in baboon lungs resulted in impaired autophagic activity in association with insufficient AMPK (5'-AMP-activated protein kinase) and increased mTORC1 (mTOR complex 1) activation. Becn1+/- lungs displayed impaired alveolarization, increased alveolar septal thickness, greater neutrophil accumulation, and increased IL-1ß concentrations when exposed to nHILI. Becn1+/- alveolar macrophages isolated from nHILI-exposed mice displayed increased expression of proinflammatory genes. In conclusion, basal autophagy is induced during alveolarization and disrupted during progression of nHILI in mice and BPD in baboons. Becn1+/- mice are more susceptible to nHILI, suggesting that preservation of autophagic activity may be an effective protective strategy in BPD.

The importance of programmed death ligand 1 gene expression, epidermal growth factor receptor gene mutations and serum epidermal growth factor receptor levels in Turkish non-small cell lung cancer patients.

BACKGROUND: This study aims to investigate the possible relationships between epidermal growth factor receptor gene mutations, serum epidermal growth factor receptor levels, programmed death ligand gene expression levels and the risks and survivals of resectable nonsmall cell lung cancer patients. METHODS: Deoxyribonucleic acid isolation was performed from peripheral blood samples and tumor tissues. The mutation analysis was performed for epidermal growth factor receptor. Programmed death ligand 1 gene expression levels were examined pathologically and histopathologically following the tissue tracing of 36 non-small cell lung cancer patients (29 males, 7 females; mean age 60.1 years; range, 41 to 79 years) and analyzed using real-time polymerase chain reaction. Epidermal growth factor receptor serum levels were assessed in all patients. RESULTS: As a result of mutation analyses in 21 patients (28.5% of all adenocarcinoma patients), epidermal growth factor receptor mutation was determined in at least one exon in six patients. In epidermal growth factor receptor mutation detected patients, programmed death ligand 1 gene expression levels were associated with lymph node metastasis (p=0.036). However, epidermal growth factor receptor mutations were not statistically significantly associated according to histopathological examination (p>0.05). Of patients carrying exon 20 (c.2303G>T) mutations, 25% had tumors with perineural invasion. There was a statistically significant association between exon 20 insertions and c.2303G>T and lymphatic invasion (p=0.02), lymph node metastasis and exon 20 insertions (p=0.03). Patients with lower serum epidermal growth factor receptor levels (<400 pg/mL) had better survival time than those with higher serum epidermal growth factor receptor levels (p=0.04). CONCLUSION: Programmed death ligand 1 gene expression and epidermal growth factor receptor mutation might have a combined effect on non-small cell lung cancer. Programmed death ligand 1 gene expression in tumor pathology may also be a significant feature for tumor progression and tumorigenesis. Serum epidermal growth factor receptor levels seem to be associated with survival.

Rectosigmoidoscopy complicated by bilateral pneumothoraces, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and pneumoderma.

Rectosigmoidoscopy is a common procedure for diagnosis and follow-up of diseases of the lower gastrointestinal system. Although the procedure is proven to be safe in experienced hands, there is always risk of complications. We report a case of bilateral pneumothoraces, pneumoperitonium, pneumoretroperitoneum, pneumomediastinum, and pneumoderma due to perforation during a rectosigmoidoscopy. Co-occurrence of all these in 1 patient is a very rare clinical condition. This report underlines the possibility of even the rarest and unexpected complications related to rectosigmoidoscopy. Endoscopist should be careful to avoid perforation, be aware of the potential complications, and be able to manage them.