Aberrant Development of Enteric Glial Cells in the Colon of Hirschsprung's Disease

Objective: The aim of this study was to explore the development of enteric glial cells (EGCs) in different segments of Hirschsprung's disease (HSCR).Methods: Colonic specimens from 35 children with HSCR were selected to analyze the relative expression of glial fibrillary acidic protein and S100 calcium-binding protein B using Western blotting and real-time fluorescence quantitative PCR. Immunofluorescence and immunohistochemical staining were performed to determine the distribution of myenteric EGCs and neuronal cells in different segments of HSCR.Results: There was a trend of diminished protein and mRNA expression of glial fibrillary acidic protein and S100 calcium-binding protein B from the proximal, dilated, and transitional segments to the aganglionic segment (p < 0.05). Immunofluorescence and immunohistochemistry showed that the EGCs in the aganglionic, transitional, and dilated colonic muscles were morphologically abnormal, which was consistent with the dysplasia of myenteric neurons.Conclusion: Aberrant development of myenteric EGCs was observed in the colon of HSCR, which may affect the survival of enteric neurons.

Intratracheal Keratinocyte Growth Factor Enhances Surfactant Protein B Expression in Mechanically Ventilated Preterm Pigs

Bronchopulmonary dysplasia (BPD) is a devastating disease of prematurity that is associated with mechanical ventilation and hyperoxia. We used preterm pigs delivered at gestational day 102 as a translational model for 26–28-week infants to test the hypothesis administering recombinant human keratinocyte growth factor (rhKGF) at initiation of mechanical ventilation will stimulate type II cell proliferation and surfactant production, mitigate ventilator induced lung injury, and reduce epithelial to mesenchymal transition considered as a precursor to BPD. Newborn preterm pigs were intubated and randomized to receive intratracheal rhKGF (20 μg/kg; n = 6) or saline (0.5 ml 0.9% saline; control; n = 6) before initiating 24 h of ventilation followed by extubation to nasal oxygen for 12 h before euthanasia and collection of lungs for histopathology and immunohistochemistry to assess expression of surfactant protein B and markers of epithelial to mesenchymal transition. rhKGF pigs required less oxygen during mechanical ventilation, had higher tidal volumes at similar peak pressures indicative of improved lung compliance, and survival was higher after extubation (83% vs. 16%). rhKGF increased surfactant protein B expression (p < 0.05) and reduced TGF-1β (p < 0.05), that inhibits surfactant production and is a prominent marker for epithelial to mesenchymal transition. Our findings suggest intratracheal administration of rhKGF at initiation of mechanical ventilation enhances surfactant production, reduces ventilator induced lung injury, and attenuates epithelial-mesenchymal transition while improving pulmonary functions. rhKGF is a potential therapeutic strategy to mitigate pulmonary responses of preterm infants that require mechanical ventilation and thereby reduce the incidence and severity of bronchopulmonary dysplasia.

Prognostic Utility of Serum Biomarkers in Intracerebral Hemorrhage: A Systematic Review

Background. Intracerebral hemorrhage (ICH) accounts for 10–20% of all strokes and is associated with high morbidity and mortality. Recent studies have identified serum biomarkers as a means to improve outcome prognostication in poor grade ICH patients. Poor prognosis of ICH patients and complex pathophysiology of the disease necessitate prognostic serum biomarkers to help guide treatment recommendations. Objective. The objective is to systematically review all biomarkers used to predict long-term functional outcome in patients with spontaneous intracerebral hemorrhage. Results. We identified 36 studies investigating the predictive utility of 50 discrete biomarkers. Data from 4865 ICH patients were reviewed. Inflammatory biomarkers (11/50) were most often studied, followed by oxidative (8/50), then neuron and astrocyte-specific (7/50). S100 calcium binding protein B, white blood cell count, and copeptin were the most often studied individual biomarkers. The prognostic utility of 23 biomarkers was analyzed using receiver operating characteristic curves. Area under the curve (AUC) values for all available biomarkers except neutrophil/lymphocyte ratio were acceptable. Twenty of the 23 biomarkers were characterized by at least one excellent AUC value. Vascular endothelial growth factor, glial fibrillary astrocyte protein, and S100 calcium binding protein B were characterized by outstanding AUC. Conclusions. We identified the inflammatory and neuron and astrocyte-specific biomarker categories as having the greatest number of significant individual biomarker predictors of long-term outcome. Further investigation utilizing cross-validation of prediction models in a second independent group and blinded assessment of outcomes for the predictive utility of biomarkers in patients with ICH is warranted.