Abstract:
BACKGROUND:Premature neonates frequently require oxygen supplementation as a therapeutic intervention that, while necessary, also exposes the lung to significant oxidant stress. We hypothesized that hyperoxia has a deleterious effect on alveolar epithelial barrier function rendering the neonatal lung susceptible to injury and/or bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS:We examined the effects of exposure to 85% oxygen on neonatal rat alveolar barrier function in vitro and in vivo. Whole lung was measured using wet-to-dry weight ratios and bronchoalveolar lavage protein content and cultured primary neonatal alveolar epithelial cells (AECs) were measured using transepithelial electrical resistance (TEER) and paracellular flux measurements. Expression of claudin-family tight junction proteins, E-cadherin and the Snail transcription factor SNAI1 were measured by Q-PCR, immunoblot and confocal immunofluorescence microscopy. RESULTS:Cultured neonatal AECs exposed to 85% oxygen showed impaired barrier function. This oxygen-induced increase in paracellular leak was associated with altered claudin expression, where claudin-3 and -18 were downregulated at both the mRNA and protein level. Claudin-4 and -5 mRNA were also decreased, although protein expression of these claudins was largely maintained. Lung alveolarization and barrier function in vivo were impaired in response to hyperoxia. Oxygen exposure also significantly decreased E-cadherin expression and induced expression of the SNAI1 transcription factor in vivo and in vitro. CONCLUSIONS:These data support a model in which hyperoxia has a direct impact on alveolar tight and adherens junctions to impair barrier function. Strategies to antagonize the effects of high oxygen on alveolar junctions may potentially reverse this deleterious effect.
journal_name
Pediatr Pulmonoljournal_title
Pediatric pulmonologyauthors
Vyas-Read S,Vance RJ,Wang W,Colvocoresses-Dodds J,Brown LA,Koval Mdoi
10.1002/ppul.23681subject
Has Abstractpub_date
2018-01-01 00:00:00pages
17-27issue
1eissn
8755-6863issn
1099-0496journal_volume
53pub_type
杂志文章abstract::To determine whether doses of ipratropium bromide (IB) greater than those usually administered by aerosol (75-250 micrograms) give a greater degree of protection from exercise-induced asthma (EIA) in children, 12 patients with chronic asthma, ages 7-13 yr, were challenged with methacholine and exercise after inhalatio...
journal_title:Pediatric pulmonology
pub_type: 杂志文章
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abstract::Little attention has been focused on the progressive pulmonary deterioration which occurs in mechanically ventilated infants with normal or mildly abnormal lungs. We hypothesized that lung function would deteriorate over a 24-hr period in anesthetized neonatal piglets with normal lungs mechanically ventilated at 2 cm ...
journal_title:Pediatric pulmonology
pub_type: 杂志文章
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abstract::Spirometric testing is traditionally achievable in children of school-age and beyond. Incorporation of interactive incentives motivates preschool children to facilitate measurement of forced expiratory indices. Validated spirometric reference standards are available for Caucasian preschoolers but lacking in Asians. We...
journal_title:Pediatric pulmonology
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
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更新日期:2006-12-01 00:00:00
abstract:OBJECTIVE:Since preventive therapies for bronchopulmonary dysplasia (BPD) are limited we treated preterm infants with azithromycin to decrease the incidence of BPD. METHODS:Infants less than 1,250 g birth weight were randomized to azithromycin or placebo within 12 hr of beginning mechanical ventilation and within 72 h...
journal_title:Pediatric pulmonology
pub_type: 杂志文章,随机对照试验
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更新日期:2011-02-01 00:00:00
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journal_title:Pediatric pulmonology
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doi:10.1002/ppul.24739
更新日期:2020-06-01 00:00:00
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.21251
更新日期:2010-07-01 00:00:00
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journal_title:Pediatric pulmonology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2005-05-01 00:00:00
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journal_title:Pediatric pulmonology
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.24063
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND:Consolidation on chest radiography is widely used as the reference standard for defining pneumonia and variability in interpretation is well known but not well explored or explained. METHODS:Three pediatric sub-specialists (infectious diseases, radiology and respiratory medicine) viewed 3,033 chest radiogra...
journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.22806
更新日期:2013-12-01 00:00:00
abstract::The single occlusion technique (SOT) is a simple and noninvasive technique for measurement of passive respiratory mechanics in infants. Reference values based on measurements of a large population of healthy infants performed outside specialized research laboratories are lacking. The aim of this study was to present r...
journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.20492
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:There is minimal literature available on the long-term outcome of pediatric non-cystic fibrosis (CF) bronchiectasis. AIM:To document 5-year outcomes of children with chest computerized tomography (CT) scan diagnosed bronchiectasis from a tertiary New Zealand (NZ) respiratory clinic. METHODS:Review of a cli...
journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.21331
更新日期:2011-02-01 00:00:00
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
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更新日期:2019-06-01 00:00:00
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journal_title:Pediatric pulmonology
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doi:10.1002/ppul.25240
更新日期:2020-12-31 00:00:00
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/(sici)1099-0496(199708)24:2<137::aid-ppul1
更新日期:1997-08-01 00:00:00
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.1950020414
更新日期:1986-07-01 00:00:00
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journal_title:Pediatric pulmonology
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doi:10.1002/ppul.20076
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.24889
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journal_title:Pediatric pulmonology
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
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更新日期:2017-10-01 00:00:00
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.21570
更新日期:2012-05-01 00:00:00
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journal_title:Pediatric pulmonology
pub_type: 临床试验,杂志文章
doi:10.1002/ppul.1950160305
更新日期:1993-09-01 00:00:00
abstract::Lung transplantation in childhood is a highly specialized clinical practice confined to a few centers around the world. Organ availability remains an important limiting factor in extending the application of this procedure to more infants, children and adolescents. The lungs are the organ most vulnerable to injury, in...
journal_title:Pediatric pulmonology
pub_type: 杂志文章,评审
doi:10.1002/ppul.20997
更新日期:2009-06-01 00:00:00
abstract::The raised lung volume technique is increasingly used to measure forced expiratory maneuvers in infants. However, there is no consensus regarding the optimal airway inflation pressure (P(inf)) required for such maneuvers, or the influence of small changes in P(inf) within and between infants. The aim of this study was...
journal_title:Pediatric pulmonology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Pediatric pulmonology
pub_type: 杂志文章,评审
doi:10.1002/ppul.24462
更新日期:2019-11-01 00:00:00
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journal_title:Pediatric pulmonology
pub_type: 杂志文章
doi:10.1002/ppul.23946
更新日期:2018-04-01 00:00:00