Abstract:
PURPOSE/AIM:Intravitreal bevacizumab (Avastin) is an irreversible vascular endothelial growth factor (VEGF) inhibitor used to treat severe retinopathy of prematurity (ROP) in extremely low gestational age neonates (ELGANs). ELGANs who are at the highest risk for developing severe ROP often experience brief intermittent hypoxia (IH) episodes which may cause oxidative damage. We tested the hypothesis that intravitreal Avastin leaks into the systemic circulation during exposure to IH and has adverse effects on biomarkers of pulmonary microvascular maturation, thus leading to pulmonary hemorrhage and long-term pulmonary sequelae. METHODS:Neonatal rats at postnatal day (PN) 0 (birth) were exposed to either: 1) hyperoxia (50% O2) or 2) neonatal IH (50% O2 with brief episodes of 12% O2) from PN0 to PN14. Room air (RA) littermates served as controls. At PN14, the time of eye opening in rats, a single dose of Avastin (0.125 mg in 5 µL) was injected into the vitreous cavity of the left eyes. A control group received equivalent volume saline. At PN23 and PN45, blood gases, lung-to-body weight ratios, histology, immunofluorescence, and lung biomarkers of angiogenesis were examined. RESULTS:At PN23, Avastin increased lung VEGF, nitric oxide derivatives (NOx), and hypoxia-inducible factor (HIF)1a in the hyperoxia-exposed groups, but decreased soluble VEGFR-1 (sVEGFR-1). At PN45, lungs from animals exposed to neonatal IH and treated with Avastin were severely hemorrhagic with morphologic changes in lung architecture consistent with chronic lung disease. This was associated with higher VEGF and NOx levels, and lower insulin-like growth factor (IGF)-I and sVEGFR-1. CONCLUSIONS:These findings prove our hypothesis that intravitreal Avastin penetrates the blood-ocular barrier in IH and alters lung biomarkers of angiogenesis. Avastin targeting of VEGF could affect normal lung development which may be exaggerated under pathologic conditions such as IH, ultimately leading to vascular permeability, vessel rupture, and pulmonary hemorrhage.
journal_name
Exp Lung Resjournal_title
Experimental lung researchauthors
Duggan TJ,Cai CL,Aranda JV,Beharry KDdoi
10.1080/01902148.2020.1866712subject
Has Abstractpub_date
2020-12-30 00:00:00pages
1-15eissn
0190-2148issn
1521-0499pub_type
杂志文章abstract:PURPOSE:This study aimed to investigate differential cell responses of alveolar epithelial cells (AECs) after treatments with lipopolysaccharide (LPS) and hydrogen peroxide (H2O2) to mimic the exposure to inflammation and oxidative stress and the mechanisms of a double-hit model of apoptosis. MATERIALS AND METHODS:AEC...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/01902148.2017.1368738
更新日期:2017-10-01 00:00:00
abstract::Direct measurements of pleural fluid hydrostatic and colloid osmotic pressures after infusion of saline, bovine serum albumin, or silicone into the pleural space were coupled with ultrastructural morphometric analyses to assess the response of pleural mesothelial cells to hydrothorax. Increases of hydrostatic pressure...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902149309064347
更新日期:1993-05-01 00:00:00
abstract::Chlorinated amines are long-lived oxidants released from inflammatory cells. They have been observed to alter the function of important inflammatory molecules. Whether they can contribute directly to the inflammatory alteration of cellular barriers is not known. Monolayers of cultured porcine pulmonary artery endothel...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148909087864
更新日期:1989-05-01 00:00:00
abstract::The production of reactive oxygen species (ROS) during hyperoxia contribute to alveolar epithelial apoptosis. In the present study, the molecular mechanisms of oxidative stress-induced alveolar epithelial cell apoptosis were investigated. The cytoprotective effects of N-acetylcysteine (NAC) were evaluated. Treatments ...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902141003678582
更新日期:2010-08-01 00:00:00
abstract::The structural features of the ovine pleura are described using light, scanning, and transmission electron microscopy. Extensive sampling of the visceral and parietal pleura revealed considerable variation in both surface morphology and pleural interstitial anatomy. Variations of mesothelial surface were encountered a...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148309055016
更新日期:1983-05-01 00:00:00
abstract::Two morphologic characteristics have been used to define the nonciliated bronchiolar epithelial cell: abundant agranular endoplasmic reticulum (AER) and membrane-bound avoid granules. To assess the ultrastructural homogeneity of this cell type in the lungs of large domestic mammals used as experimental models in pulmo...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148009069645
更新日期:1980-06-01 00:00:00
abstract::A tandem repeat region in the second intron of the K-ras gene has been reported to be a possible regulatory site for transcription. In this study, a second protein-binding site was identified and characterized. It lies downstream (nucleotides 463 to 509) of the tandem repeat region. A T--> C base variation at nucleoti...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/0190214049049552
更新日期:2005-03-01 00:00:00
abstract::Aims:Bronchopulmonary dysplasia (BPD) is characterized by alveolarization arrest. During alveolarization, alveolar myofibroblasts are thought to migrate into the septal tips and elongate secondary septa. Lipopolysaccharide (LPS) exposure has been reported to disrupt directional migration and final location of alveolar...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/01902148.2019.1711464
更新日期:2020-01-01 00:00:00
abstract::Neutrophilic inflammation is responsible for much of the tissue damage seen in many lung diseases. For resolution of inflammation to occur, neutrophils must die by apoptosis, allowing their recognition and removal by macrophages. The molecular events controlling this important regulatory step are poorly understood, in...
journal_title:Experimental lung research
pub_type: 杂志文章,评审
doi:10.1080/01902140701756778
更新日期:2007-12-01 00:00:00
abstract::We set out to determine whether or not the "mucolytic" drug N-acetylcysteine would speed the reversal of cigarette smoke-induced secretory-cell hyperplasia to normal, similar to that found previously for two nonsteroidal antiinflammatory drugs. Cigarette smoke alone significantly (p less than 0.01) increased the numbe...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148809062848
更新日期:1988-01-01 00:00:00
abstract::Tannic acid was used as a mordant to enhance the preservation of lung phospholipids during fixation and processing for electron microscopy. We found multilamellar bodies within alveolar septa (including type I pneumocytes, capillary endothelial cells, and interstitium) which have not been described previously and whic...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148009065460
更新日期:1980-08-01 00:00:00
abstract:BACKGROUND:Mechanisms linking behavioral stress and inflammation are poorly understood, mainly in distal lung tissue. OBJECTIVE:We have investigated whether the forced swim stress (FS) could modulate lung tissue mechanics, iNOS, cytokines, oxidative stress activation, eosinophilic recruitment, and remodeling in guinea...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148.2012.704484
更新日期:2012-09-01 00:00:00
abstract::The role of bombesin was investigated in the course of the pulmonary inflammation and fibrosis (PF) elicited by the intratracheal (IT) or intravenous (i.v.) administration of bleomycin in mice. Bleomycin-induced alveolitis was associated with an accumulation of cells, presumably macrophages, containing bombesin, as ev...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902149509068829
更新日期:1995-03-01 00:00:00
abstract::Acute exposure to NO2 is reported to disrupt tight junctions in lung epithelium. We have studied the effects of chronic NO2 exposure and recovery breathing clean air to tight junctions of distal airway and alveolar epithelium. Syrian Golden hamsters were exposed to NO2 (30 PPM) for 5 or 9 months and a group of those a...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148609064295
更新日期:1986-01-01 00:00:00
abstract::This study describes the morphology of the adaptive response of the pulmonary parenchyma after the resection of lung tissue. Rats aged 23 days were subjected to the bilobectomy of the right upper and middle lobes representing 25% of the total lung volume. On the postoperative Days 1, 4, 6, 9, 12, 18, and 30, the lungs...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148209039246
更新日期:1982-12-01 00:00:00
abstract::An IgM monoclonal antibody (1D9/B3) is characterized, which specifically recognizes basal cells of the upper airway epithelium. Although morphological features have been used to follow cell lineage and differentiation, an objective assessment of differentiation can be enhanced by characterizing the expression of speci...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902149509031741
更新日期:1995-01-01 00:00:00
abstract::We hypothesized that replication-deficient adenovirus (Ad), when complexed with plasmid DNA (pl) and cationic liposomes (L), would enhance liposome-mediated gene transfer in cultured human airway epithelial cells. Pl/L/Ad complexes were formed using charge-charge interactions. A gel electrophoresis retardation assay s...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/019021400269862
更新日期:2000-04-01 00:00:00
abstract::Acute lung injury (ALI) is often associated with sepsis and is the most common cause of acute respiratory failure. The authors evaluated the role of the heme oxygenase (HO)/carbon monoxide (CO) system on lung injury in a cecal ligation and puncture (CLP)-induced mouse model of ALI. The authors established CLP-induced ...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148.2012.660559
更新日期:2012-05-01 00:00:00
abstract::The effects of activated leukocytes on surfactant function and composition were examined to better define the mechanisms by which acute inflammation contributes to respiratory distress syndrome (ARDS). Peripheral blood leukocytes from healthy volunteers were incubated in vitro with surfactant for 4 hours: (1) in the a...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/019021499270042
更新日期:1999-10-01 00:00:00
abstract::The authors compared the ability of a single dose of the proenzyme single-chain urokinase (scuPA), low-molecular-weight urokinase, tissue plasminogen activator (tPA), or a mutant site-inactive scuPA to resolve intrapleural loculations at 72 to 96 hours after tetracycline-induced pleural injury in rabbits. Both scuPA a...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/01902140701703333
更新日期:2007-10-01 00:00:00
abstract::ABSTRACT During fetal development physiological stretching helps drive lung growth and maturation. At birth, the α-subunit of the alveolar epithelial sodium channel (α-ENaC) is a critical factor in helping to facilitate clearance of lung fluid during the perinatal period. The effects of stretch, however, on α-ENaC exp...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148.2014.934410
更新日期:2014-10-01 00:00:00
abstract:AIM OF THE STUDY:Long-term exposure to cigarette smoke generates chronic obstructive pulmonary disease (COPD) in guinea pigs, but a comprehensive evaluation of changes in lung function, as assessed by barometric whole body plethysmography (WBP), is lacking. MATERIALS AND METHODS:Female guinea pigs were exposed to the ...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/01902148.2017.1294632
更新日期:2017-03-01 00:00:00
abstract::In a recent study of the sheep tracheal lobe model, we have demonstrated that surface chemistry modification of quartz by aluminum lactate significantly alters the biological activity of quartz for at least 2 months after exposure. In the present study, we have extended our observations of the biological reaction of t...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148709064319
更新日期:1987-01-01 00:00:00
abstract::Chymase is a chymotrypsin-like serine protease that is present in mast cells. Its activities include various effects associated with inflammatory responses. But little is known about the effects of chymase in pulmonary fibrosis. The mouse silicosis model was induced by intratracheal injection of 10 mg silica. The Ashc...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148.2010.520815
更新日期:2011-03-01 00:00:00
abstract::A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/01902140490463142
更新日期:2004-07-01 00:00:00
abstract::Mechanical ventilation (MV) is well known to potentially cause ventilator-associated lung injury (VALI). It has also been reported recently that activation of invariant natural killer T (iNKT) cells is involved in the onset/progression of airway inflammation. We analyzed the roles of inflammatory cells, including iNKT...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148.2013.854518
更新日期:2014-02-01 00:00:00
abstract::Intraphagosomal pH in rabbit alveolar macrophages was studied using amorphous silica particles (FSP) and yeast particles (FYP) labeled with fluorescein. The pH was estimated from the quotient between the fluorescence intensity at wavelength 519 nm with excitation at wavelengths 495 and 450 nm. Within a factor of 10, p...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902148909069608
更新日期:1989-01-01 00:00:00
abstract::A deletional analysis of the SP-A1 promoter in NCI-H441 cells was performed to identify potential cis-acting elements involved in phorbol ester-mediated repression of human SP-A transcription. The phorbol ester TPA reduced SP-A1 and SP-A2 promoter activity to approximately 35% to 45% compared to that of control cells....
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/019021400408272
更新日期:2000-07-01 00:00:00
abstract::The Ca(2+)-mobilizing actions of adenosine 5'-triphosphate (ATP), bradykinin, and histamine were compared in phenotypically distinct human nasal epithelial (HNE) cell types and as a function of time in cell culture. Single-cell measurements of intracellular free Ca2+ (Ca2+i, Fura-2 fluorescence) were recorded in cilia...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.1080/019021499270196
更新日期:1999-06-01 00:00:00
abstract::Endothelin-1 (ET-1) has constrictor and mitogenic effects on airway smooth muscle strips and cultured cells, respectively. This study addresses the type of the ET receptor subtype(s) present on ovine airway smooth muscle cells and the possibility of autocrine effects. The expression of the preproendothelin-1 gene was ...
journal_title:Experimental lung research
pub_type: 杂志文章
doi:10.3109/01902149509023719
更新日期:1995-05-01 00:00:00