Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the leading causes of morbidity and mortality in babies born prematurely, yet there is no curative treatment. In recent years, a number of inhibitors against TGFß signaling have been tested for their potential to prevent neonatal injury associated with hyperoxia, which is a contributing factor of BPD. In this study, we assessed the contribution of activin A-a member of the TGFß superfamily-to the development of hyperoxia-induced lung injury in neonatal mice. METHODS: We placed newborn C57Bl6 mouse pups in continuous hyperoxia (85% O2) to mimic many aspects of BPD including alveolar simplification and pulmonary inflammation. The pups were administered activin A receptor type IIB-Fc antagonist (ActRIIB-Fc) at 5 mg/kg or follistatin at 0.1 mg/kg on postnatal days 4, 7, 10, and 13. RESULTS: Treatment with ActRIIB-Fc and follistatin protected against hyperoxia-induced growth retardation. ActRIIB-Fc also reduced pulmonary leukocyte infiltration, normalized tissue: airspace ratio and increased septal crest density. These findings were associated with reduced phosphorylation of Smad3 and decreased matrix metalloproteinase (MMP)-9 activity. CONCLUSION: This study suggests that activin A signaling may contribute to the pathology of bronchopulmonary dysplasia.

Nasogastric tube insertion followed by intravenous and oral erythromycin in refractory nausea and vomiting secondary to paraneoplastic gastroparesis: A case report.

BACKGROUND: Gastroparesis is an under-recognised cause of refractory nausea and vomiting in patients with malignancy. The most common aetiologies are paraneoplastic and postsurgical dysmotility. There are little data on the efficacy of treatment to direct the management of patients with this symptom. We present a case and brief summary of current literature. CASE PRESENTATION: We present the case of a 72-year-old patient with metastatic neuroendocrine carcinoma of the pancreas with dehydration and renal impairment secondary to nausea and vomiting. Replacement of duodenal stent, gastroscopy, endoscopic retrograde cholangiopancreatogram and gastric motility studies revealed gastroparesis rather than mechanical obstruction. CASE MANAGEMENT: The patient was transferred to an inpatient palliative care unit for symptom management where a nasogastric tube was inserted, followed by intravenous erythromycin with excellent improvement in symptoms and oral intake. He was switched to oral erythromycin with ongoing effect. CASE OUTCOME: With stabilisation of symptoms and renal function, the patient was able to be discharged with maintenance of good symptomatic control. CONCLUSIONS: Further research is needed into the management of gastroparesis in palliative care patients. In particular, we suggest that initial drainage with a nasogastric tube followed by a course of erythromycin warrants further study.

Human amnion epithelial cells modulate hyperoxia-induced neonatal lung injury in mice.

BACKGROUND AIMS: Human amnion epithelial cells (hAECs) prevent pulmonary inflammation and injury in fetal sheep exposed to intrauterine lipopolysaccharide. We hypothesized that hAECs would similarly mitigate hyperoxia-induced neonatal lung injury. METHODS: Newborn mouse pups were randomized to either normoxia (inspired O2 content (FiO2) = 0.21, n = 60) or hyperoxia (FiO2 = 0.85, n = 57). On postnatal days (PND) 5, 6 and 7, hAECs or sterile saline (control) was administered intraperitoneally. All animals were assessed at PND 14. RESULTS: Hyperoxia was associated with lung inflammation, alveolar simplification and reduced postnatal growth. Administration of hAECs to hyperoxia-exposed mice normalized body weight and significantly attenuated some aspects of hyperoxia-induced lung injury (mean linear intercept and septal crest density) and inflammation (interleukin-1α, interleukin-6, transforming growth factor-ß and platelet-derived growth factor-ß). However, hAECs did not significantly alter changes to alveolar airspace volume, septal tissue volume, tissue-to-airspace ratio, collagen content or leukocyte infiltration induced by hyperoxia. CONCLUSIONS: Intraperitoneal administration of hAECs to neonatal mice partially reduced hyperoxia-induced lung inflammation and structural lung damage. These observations suggest that hAECs may be a potential therapy for neonatal lung disease.