RESUMO
Surfaxin (lucinactant), a peptide-based surfactant consisting of dipalmitoylphosphatidylcholine (DPPC) plus KL(4) (sinapultide) (a synthetic peptide modeled after human surfactant protein-B), is effective in treating respiratory distress syndrome in preterm infants. Our goal was to determine the uptake and effects of Surfaxin on human pulmonary type II cells isolated from fetal tissue and other lung cell types. Based on previous published reports, we hypothesized that this exogenous synthetic surfactant would have little effect on type II cell surfactant-related physiological features. Human type II cells and A549 and NCI-H441 adenocarcinoma cells incorporated (3)H-KL(4) and (14)C-DPPC components in Surfaxin, but with different kinetics. Fractionation of NCI-H441 and A549 cellular components indicated that the highest specific activity of (3)H-KL(4) was present in the 18,000g cellular fraction (which contains vesicles and lysosomes). The number of lamellar bodies (LBs) appears to increase in human type II cells incubated in the presence of Surfaxin when visualized by light microscopy, while LB structure (determined by electron microscopy) was not altered. Expression of endogenous surfactant protein (SP-A, SP-B, and SP-C) mRNA levels in human type II cells was not altered by the presence of Surfaxin. We conclude that while human type II cells and other lung cell types can incorporate the components of Surfaxin, the surfactant-related physiological functions of these cells are not altered.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/farmacocinética , Peptídeos/metabolismo , Proteínas/farmacocinética , Alvéolos Pulmonares/embriologia , Mucosa Respiratória/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Northern Blotting , Brefeldina A/farmacologia , Linhagem Celular Tumoral , Células Cultivadas , Meios de Cultura Livres de Soro/química , Combinação de Medicamentos , Exocitose/efeitos dos fármacos , Exocitose/fisiologia , Humanos , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intercelular , Líquido Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Microscopia Eletrônica , Organelas/efeitos dos fármacos , Organelas/ultraestrutura , Peptídeos/efeitos dos fármacos , Peptídeos/genética , Inibidores da Síntese de Proteínas/farmacologia , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/metabolismo , RNA Mensageiro/genética , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/embriologiaRESUMO
BACKGROUND: Current literature has been inconsistent in demonstrating that minimizing the duration of mechanical ventilation in very-low-birth-weight (VLBW) newborns reduces lung damage. OBJECTIVE: To determine if introduction of bubble nasal CPAP (bnCPAP), early surfactant treatment, and rapid extubation (combined bnCPAP strategy) in our community-based neonatal ICU reduced bronchopulmonary dysplasia (BPD). METHODS: This was a 7-year retrospective,single-institution review of respiratory outcomes in 633 VLBW babies before and after introduction of the combined bnCPAP strategy. Coincident changes in newborn care were taken into account with a logistic regression model. RESULTS: The average percentage of VLBW newborns with BPD decreased to 25.8% from 35.4% (P = .02), reaching a minimum in the last post-bnCPAP year of22.1% (P = .02). When other coincident changes in newborn care during the study years were taken into account, VLBW babies in the post-bnCPAP years had a 43% lower chance of developing BPD(P = .003, odds ratio 0.43, 95% CI 0.25 0.75). Decreases occurred in mechanical ventilation and the percentage of infants discharged on diuretics and on supplemental oxygen. Among the subset of extremely-low-birth-weight newborns, improved respiratory outcomes in the post-bnCPAP years,as compared to outcomes in the pre-bnCPAP years, included an increase in the percentage alive and off mechanical ventilation at 1 week postnatal age (P < .001), a more rapid extubation rate(P < .03), a decrease in the median days on mechanical ventilation (P = .002), and a decrease in the percentage with BPD plus died (P = .01). Post-bnCPAP extremely-low-birth-weight babies had a statistically significant decrease in retinopathy of prematurity, an increase in low-grade intraventricular hemorrhage, and a decrease in ductal ligations. CONCLUSIONS: A combined BnCPAP strategy may contribute to a reduction of BPD, after adjusting for concurrent treatments.