Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants

2007 ◽  
Vol 292 (1) ◽  
pp. E308-E313 ◽  
Author(s):  
Ettore Capoluongo ◽  
Franco Ameglio ◽  
Paola Lulli ◽  
Angelo Minucci ◽  
Concetta Santonocito ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Active Form ◽  
Protein A ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
Oxygen Administration ◽  
Severity Scores ◽  
Igf I ◽  
Postmenstrual Age ◽  
Preterm Newborns

Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF-I) in sera. They also present higher free IGF-I concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the active form of IGF-I, namely free IGF-I. The present study analyzes the ELF concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns developing or not BPD, defined as O2 dependence at 36 wk postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were analyzed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4 compared with newborns without BPD. A nonsignificant trend between these 2 days was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-I or PAPP-A when individually evaluated. A multivariate analysis confirmed the significance for free IGF-I on day 4, whereas the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indexes of disease severity, such as hours of oxygen administration, days of hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF-I and PAPP-A appears to be a useful marker for lung injury of premature newborns.

Interaction of transferrin saturated with iron with lung surfactant in respiratory failure

1994 ◽  
Vol 77 (2) ◽  
pp. 757-766 ◽  
Author(s):  
M. Hallman ◽  
A. Sarnesto ◽  
K. Bry
Keyword(s):  
Respiratory Failure ◽  
Surface Activity ◽  
Lung Surfactant ◽  
Protein A ◽  
Surfactant Protein ◽  
Lung Damage ◽  
Epithelial Lining ◽  
Surface Absorption ◽  
Epithelial Lining Fluid

Proteins that decrease the surface activity of surfactant accumulate in epithelial lining fluid in respiratory failure. The aim of this study was to isolate a surfactant inhibitor from the airways of rabbits in acute respiratory failure induced by bronchoalveolar lavage (BAL). This inhibitor was identified as being transferrin (TF). Unlike serum TF, TF recovered in respiratory failure was saturated with iron (Fe(3+)-TF). Fe(3+)-TF decreased the surface activity of normal surfactant in vitro, whereas iron-free TF had no effect. In the presence of H2O2 and a reducing agent, Fe(+3)-TF inactivated the surfactant complex: the surface absorption rate was decreased, immunoreactive surfactant protein A was decreased, and malondialdehyde was formed. The acute effects of Fe(3+)-TF and iron-free TF applied to the airways were studied in animal models. In respiratory failure induced by BAL, Fe(3+)-TF deteriorated respiratory failure, whereas iron-free TF had no effect. In respiratory failure induced by hyperoxia for 48 h, administration of iron-free TF ameliorated the respiratory failure and improved the surface activity in BAL. We propose that Fe(3+)-TF accumulating in epithelial lining fluid during lung damage contributes to surfactant inhibition and promotes the formation of free radicals that inactivate the surfactant system.

Bronchopulmonary dysplasia and postnatal growth following extremely preterm birth

2020 ◽  
pp. fetalneonatal-2020-320816
Author(s):  
Theodore Dassios ◽  
Emma E Williams ◽  
Ann Hickey ◽  
Catey Bunce ◽  
Anne Greenough
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Head Circumference ◽  
Outcome Measure ◽  
Postnatal Growth ◽  
Z Score ◽  
Main Outcome Measure ◽  
Extremely Preterm ◽  
Postmenstrual Age ◽  
Extremely Preterm Birth ◽  
Current Incidence

ObjectivesTo report the current incidence of bronchopulmonary dysplasia (BPD) and to compare changes in weight and head circumference between infants who developed BPD and infants who did not.DesignRetrospective, whole-population study.SettingAll neonatal units in England between 2014 and 2018.PatientsAll liveborn infants born <28 completed weeks of gestation.InterventionsThe change in weight z-score (ΔWz) was calculated by subtracting the birthweight z-score from the weight z-score at 36 weeks postmenstrual age (PMA) and at discharge. The change in head circumference z-score (ΔHz) was calculated by subtracting the birth head circumference z-score from the head circumference z-score at discharge.Main outcome measureBPD was defined as the need for any respiratory support at 36 weeks PMA.Results11 806 infants were included in the analysis. The incidence of BPD was 57.5%, and 18.9% of the infants died before 36 weeks PMA. The median (IQR) ΔWz from birth to 36 weeks PMA was significantly smaller in infants who developed BPD (−0.69 (−1.28 to −0.14), n=6105) than in those who did not develop BPD (−0.89 (−1.40 to −0.33), n=2390; adjusted p<0.001). The median (IQR) ΔHz from birth to discharge was significantly smaller in infants who developed BPD (−0.33 (−1.69 to 0.71)) than in those who did not develop BPD (−0.61 (−1.85 to 0.35); adjusted p<0.001).ConclusionsPostnatal growth was better in infants diagnosed with BPD compared with infants without BPD possibly due to more aggressive nutrition strategies.

scholarly journals Pharmacodynamics of Moxifloxacin and Levofloxacin at Simulated Epithelial Lining Fluid Drug Concentrations against Streptococcus pneumoniae

2004 ◽  
Vol 48 (4) ◽  
pp. 1215-1221 ◽  
Author(s):  
Naomi R. Florea ◽  
Pamela R. Tessier ◽  
Cuilian Zhang ◽  
Charles H. Nightingale ◽  
David P. Nicolau
Keyword(s):  
Streptococcus Pneumoniae ◽  
Fluoroquinolone Resistance ◽  
Epithelial Lining ◽  
Time Curve ◽  
Bacterial Killing ◽  
Epithelial Lining Fluid ◽  
Log Reduction ◽  
Development Of Resistance ◽  
Drug Concentrations

ABSTRACT Recent clinical failures associated with levofloxacin treatment for Streptococcus pneumoniae infections and growing evidence of frequent mutations in the isolate population have led to increased concerns regarding fluoroquinolone resistance. Our objective was to characterize the efficacies of levofloxacin and moxifloxacin against various genotypes of S. pneumoniae after simulated bronchopulmonary exposures. An in vitro model was used to simulate a levofloxacin concentration of 500 mg and a moxifloxacin concentration of 400 mg, which were previously determined to be the concentrations in the epithelial lining fluid of older adults receiving once-daily dosing. The effects of the drugs were tested against six S. pneumoniae containing various mutations. Bacterial density and resistance were quantitatively assessed over 48 h. The S. pneumoniae isolate with no mutation displayed a 4-log reduction in CFU after treatment with both agents and did not develop resistance. Isolates containing the parC or parE mutation or both mutations regrew and developed resistance when they were exposed to levofloxacin, despite an unbound area under the concentration-time curve (AUC):MIC ratio of ∼100. When the isolate containing the parC and gyrA mutations was exposed to levofloxacin, there was a half-log reduction in the number of CFU compared to that for the control, but the isolate subsequently regrew. Likewise, levofloxacin did not kill the isolate containing the parC, gyrA, and parE mutations. Moxifloxacin sustained the killing of all bacterial isolates tested without the development of resistance. Levofloxacin did not sustain bacterial killing and did not prevent the emergence of further resistance in mutants with the parC or parE mutation or both mutations, even though an unbound AUC:MIC ratio for exposure well above the breakpoint of 30 to 40 established in the literature for S. pneumoniae was maintained. Moxifloxacin was effective against all isolates tested, despite the presence of isolates with two- and three-step mutations, for which the MICs were increased.

scholarly journals Crystal structure of an active form of RAS protein, a complex of a GTP analog and the HRAS p21 catalytic domain.

1990 ◽  
Vol 87 (12) ◽  
pp. 4849-4853 ◽  
Author(s):  
A. T. Brunger ◽  
M. V. Milburn ◽  
L. Tong ◽  
A. M. deVos ◽  
J. Jancarik ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Catalytic Domain ◽  
Active Form ◽  
Protein A ◽  
Ras Protein

scholarly journals Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 5. Oseltamivir Carboxylate

2016 ◽  
Vol 60 (8) ◽  
pp. 5085-5087 ◽  
Author(s):  
Danilo Cesar Galindo Bedor ◽  
Sandrine Marchand ◽  
Isabelle Lamarche ◽  
Julian Laroche ◽  
Davi Pereira de Santana ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Area Under The Curve ◽  
Pulmonary Delivery ◽  
Epithelial Lining ◽  
Oseltamivir Carboxylate ◽  
Epithelial Lining Fluid

ABSTRACTThe aim of this study was to determine the biopharmaceutical characteristics of oseltamivir carboxylate (OC) after pulmonary delivery. After OC bolus and intratracheal nebulization (NEB) in rats, blood was collected and bronchoalveolar lavages (BALs) were performed. Epithelial lining fluid (ELF) concentrations were estimated from BAL fluid. The area under the curve (AUC) ratio for ELF to plasma was 842 times higher after NEB than after intravenous (i.v.) administration, indicating that OC nebulization offers a biopharmaceutical advantage over i.v. administration.

Endothelin-1 level in epithelial lining fluid of patients with acute respiratory distress syndrome

Respirology ◽  
2007 ◽  
Vol 12 (5) ◽  
pp. 740-743 ◽  
Author(s):  
Yasushi NAKANO ◽  
Sadatomo TASAKA ◽  
Fumitake SAITO ◽  
Wakako YAMADA ◽  
Yoshiki SHIRAISHI ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
Endothelin 1
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