Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032290 (aspiration pneumonia)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastric juice aspiration syndrome (GJA-S, Mendelson syndrome) was studied experimentally in pigs. Following instillation of gastric juice into the right main bronchus necrosis of pneumocytes and bronchiolar epithelium occurred with activation of complement and a prostaglandin E releasing system (possibly the kinin system). Cell necrosis was followed by loss of surfactant and formation of hyaline membranes, rich in immunoglobulin M. The alveolar damage organized, resulting in intraalveolar and interstitial fibrosis. The causative agents were found to be both gastric hydrochloric acid and pepsin. Pretreatment with H2-, or acetylcholine-receptor-antagonists (cimetidine or pirenzepin) as well as buffering of the gastric juice to a neutral pH did not prevent lung fibrosis. If a mixture of aluminium hydroxide, magnesium carbonate and oxethazaine was added to the aspirate, development of lung fibrosis was prevented, but severe granulomatous reaction with foreign body giant cells within both lungs evolved. Kallikrein inhibitor, when administered intravenously not later than 3 min after artificial aspiration, protected the left lung completely and large areas of the right. If infused within 60-90 s complete protection of the left lung and the right upper lobe was achieved. In the majority of the animals a mild focal fibrosis developed in the right lower lobe; in one experiment both lungs were devoid of fibrotic areas. If Kallikrein inhibitor was infused 5 min prior to aspiration, lung fibrosis was not prevented.
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PMID:The gastric juice aspiration syndrome (Mendelson syndrome). Aspects of pathogenesis and treatment in the pig. 308 34

Chronic inflammation induces lymphangiogenesis and blood vessel remodelling. Since aged pneumonia patients often have repeated episodes of aspiration pneumonia, the pathogenesis may involve chronic inflammation. For lymphangiogenesis, VEGFR-3 and its ligand VEGF-C are key factors. No previous studies have examined chronic inflammation or vascular changes in aspiration pneumonia or its mouse models. In lung inflammation, little is known about the effect of blocking VEGFR-3 on lung lymphangiogenesis and, moreover, its effect on the disease condition. This study aimed to establish a mouse model of aspiration pneumonia, examine the presence of chronic inflammation and vascular changes in the model and in patients, and evaluate the effect of inhibiting VEGFR-3 on the lymphangiogenesis and disease condition in this model. To induce aspiration pneumonia, we repeated inoculation of pepsin at low pH and LPS into mice for 21-28 days, durations in which bronchioalveolar lavage and plasma leakage in the lung suggested the presence of exaggerated inflammation. Conventional and immunohistochemical analysis of tracheal whole mounts suggested the presence of chronic inflammation, lymphangiogenesis, and blood vessel remodelling in the model. Quantitative RT-PCR of the trachea and lung suggested the involvement of lymphangiogenic factor VEGF-C, VEGFR-3, and pro-inflammatory cytokines. In the lung, the aspiration model showed the presence of chronic inflammation and exaggerated lymphangiogenesis. Treatment with the VEGFR inhibitor axitinib or the VEGFR-3 specific inhibitor SAR131675 impaired lymphangiogenesis in the lung and improved oxygen saturation in the aspiration model. Since the lung is the main site of aspiration pneumonia, the changes were intensive in the lung and mild in the trachea. Human lung samples also showed the presence of chronic inflammation and exaggerated lymphangiogenesis, suggesting the relevance of the model to the disease. These results suggest lymphatics in the lung as a new target of analysis and therapy in aspiration pneumonia.
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PMID:Chronic inflammation, lymphangiogenesis, and effect of an anti-VEGFR therapy in a mouse model and in human patients with aspiration pneumonia. 2534 79