Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigation of the composition and significance of individual components of the surfactant indicated that besides phospholipids an important role is played also by surfactant proteins. They aid not only the reduction of the surface tension of the lungs (SP-B, SP-C), but serve also in regulation of surfactant secretion (SP-A) and in local defense and immune responses in the lungs (SP-A and SP-D). Impairments of surfactant were discovered not only in RDS, but also in cases of meconium aspiration, congenital diaphragmatic hernia, pneumonia, pulmonary edema, idiopathic fibrosis of the lungs, alveolar proteinosis, pneumothorax, and bronchial asthma. Therapy by means of exogenous surfactant was proved effective in therapy of RDS. Occasional cases of exogenous surfactant therapy in other pulmonary diseases are auspicious, it is necessary, though, to develop and produce a sufficient amount of exogenous surfactant of high quality and at an acceptable price and to find an optimal manner of surfactant administration into the lungs. A significant perspective is anticipated to utilization of intrapulmonary administration of the exogenous surfactant as a carrier of further active substances for local administration into the lungs. (Ref. 36.)
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PMID:[The pulmonary surfactant factor. Current knowledge, research trends and use in clinical practice]. 788 59

Neonates with congenital diaphragmatic hernia (DH) die of pulmonary hypoplasia and persistent pulmonary hypertension. We used immunohistochemical localization of alpha-smooth muscle actin (alpha-SMA), platelet endothelial cell adhesion molecule (PECAM)-1, thyroid transcription factor (TTF)-1, surfactant protein (SP) A, SP-C, and competitive RT-PCR quantitation of TTF-1, SP-A, SP-C, and alpha-SMA mRNA expression to characterize the epithelial and vascular phenotype of lungs from ICR fetal mice with a nitrofen-induced DH. Nitrofen (25 mg) was gavage fed to pregnant mice on day 8 of gestation. Fetal mice were delivered on day 17. The diaphragm was examined for a defect, and the lungs were either fixed, sectioned, and immunostained or processed for mRNA isolation. In comparison with control lungs, DH lungs showed increased expression of alpha-SMA mRNA, fewer and more muscular arterioles (alpha-SMA), less well-developed capillary networks (PECAM-1), delayed epithelial development marked by a persistence of TTF-1 in the periphery, and decreased SP-A mRNA and SP-A expression. These data suggest that in the murine nitrofen-induced DH, as in human congenital DH, pulmonary insufficiency is due to an inhibition of peripheral pulmonary development including terminal airway and vascular morphogenesis.
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PMID:Inhibition of vascular and epithelial differentiation in murine nitrofen-induced diaphragmatic hernia. 957 82

The hypoplastic lung in congenital diaphragmatic hernia (CDH) has both a quantitative and qualitative reduction in surfactant. Recently, the role of oxygen (O2) as a regulator of pulmonary surfactant-associated protein (SP) gene expression has been reported. The mRNA level of SP has been demonstrated to be increased in the lungs of animals exposed to hyperoxia. The aim of this study was to investigate SP mRNA expression in hypoplastic CDH lung in rats during mechanical ventilation in order to determine the effect of O2 on SP synthesis in CDH. A CDH model was induced in pregnant rats following administration of nitrofen. The newborn rats with CDH and controls were intubated and ventilated. Ventilation was continued for 6 h under 100% oxygen. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the relative amounts of mRNA expression of SP-A, SP-B, SP-C, and SP-D. Relative amounts of SP-A, SP-B, and SP-D mRNA expression in CDH lung were significantly decreased compared to controls at birth and 6 h after ventilation. There was no significant difference in SP-C mRNA expression between CDH animals and controls. Upregulated mRNA expression of SP-A, SP-B, and SP-D in lungs of control animals at 6 h after ventilation suggests that oxygenation accelerates postnatal SP synthesis in normal lungs. The inability of O2 to increase SP mRNA expression in hypoplastic CDH lung suggests that the hypoplastic lung is not responsive to increased oxygenation for the synthesis of SP.
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PMID:Effect of hyperoxia on surfactant protein gene expression in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats. 1105 44

Neonates with congenital diaphragmatic hernia (CDH) suffer from a diaphragmatic defect, lung hypoplasia, and pulmonary hypertension, with poor lung function forming the major clinical challenge. Despite prenatal diagnosis and advanced postnatal treatment strategies, the mortality rate of CDH is still high. CDH has been subject of extensive research over the past decades, but its etiology remains unknown. A major problem with CDH is the failure to predict the individual response to treatment modalities like high-frequency ventilation, inhaled nitric oxide, and extracorporeal membrane oxygenation. In this study, we tested the possibility that CDH lungs are surfactant protein deficient, which could explain the respiratory failure and difficulties in treating CDH infants. We investigated this hypothesis in the nitrofen-induced CDH rat model and assessed the cellular concentrations of surfactant protein (SP)-A, -B, and -C mRNA with a quantitative radioactive in situ hybridization technique. No differences were observed between control and CDH lungs for SP mRNA expression patterns. The cellular concentration (mean OD) of SP-A and SP-B mRNA was similar at all stages whereas the mean OD of SP-C mRNA and the volume fraction of cells (% Area) expressing SP mRNA was higher in CDH lungs at term. Immunohistochemical analysis revealed no differences between control and CDH lungs for SP protein expression. No differences in the mean OD or % Area for the SP mRNAs were found between the ipsi- and contralateral side of CDH lungs. We conclude that there is no primary deficiency of surfactant proteins in the nitrofen-induced CDH rat model.
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PMID:Pulmonary surfactant protein A, B, and C mRNA and protein expression in the nitrofen-induced congenital diaphragmatic hernia rat model. 1290 92

Congenital diaphragmatic hernia (CDH) occurs in approximately 1:2,500 human births and has high morbidity and mortality rates, primarily due to pulmonary hypoplasia and pulmonary hypertension. Tracheal occlusion (TO), in experimental animals, distends lungs and increases lung growth and alveolar type I cell maturation but decreases surfactant components and reduces alveolar type II cell density. We examined effects of CDH and CDH+TO on lung growth and maturation in fetal rats. To induce CDH, we administered nitrofen (100 mg) to dams at 9.5 days of gestation. We compared lungs from fetuses with CDH, CDH+TO, and those exposed to nitrofen without CDH. CDH decreased lung wet weight bilaterally (P < 0.0001) and DNA content in lung ipsilateral to CDH (P < 0.05). CDH+TO significantly increased lung wet weights bilaterally; DNA content was intermediate between CDH and NC. To evaluate effects on the distal pulmonary epithelium, we examined surfactant mRNA and protein levels, type I and II cell-specific markers (RTI(40) and RTII(70), respectively), and transcriptional regulator thyroid transcription factor-1 (TTF-1). Decreased lung distension (due to CDH) increased SP-C mRNA and TTF-1 protein expression and reduced RTI(40) (P < 0.05 for all). Increased lung distension (due to CDH+TO) reduced expression of SP mRNAs and pro-SP-C and TTF-1 proteins and enhanced expression of RTI(40) (mRNA and protein; P < 0.05 for all). We conclude that CDH+TO partially reverses effects of CDH; it corrects the pulmonary hypoplasia and restores type I cell differentiation but adversely affects SP expression in type II cells. These effects may be mediated through changes in TTF-1 expression.
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PMID:Congenital diaphragmatic hernia, tracheal occlusion, thyroid transcription factor-1, and fetal pulmonary epithelial maturation. 1576 45