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)

Neonates with congenital diaphragmatic hernia (CDH) experience a high mortality despite intensive medical and surgical management. The associated pulmonary hypoplasia is accompanied by an underlying biochemical deficiency that bears similarity to respiratory distress syndrome (RDS) in the premature newborn. Using therapies extrapolated from those used to treat RDS, the authors have previously shown correction of the immature pulmonary biochemical indices in the nitrofen rat CDH model. This study investigates the functional and histological outcome of prenatal hormone therapy on CDH rats. Compared with saline-treated CDH controls, dexamethasone-treated CDH animals achieved significant increases in lung distensibility (P = .0006) and functional residual capacity (P = .004); CDH rats treated with combined dexamethasone and thyrotropin-releasing hormone (TRH) showed improved functional residual capacity (P = .043) and alveolar stability (P = .025); CDH animals treated with TRH alone (TRH-CDH) showed no improvement in any parameter tested. Histologically, the lungs from dexamethasone- and dexamethasone-TRH-treated CDH animals showed changes that included narrow septal walls, increased air saccule size, and thinning of the pulmonary interstitium compared with the lungs of saline or TRH-CDH rats, which were developmentally arrested at the canalicular stage. Lung weights and lung weight-body weights ratios were similar in all CDH rats, confirming that treatment did not impair pulmonary growth. These results support the potential clinical use of prenatal pharmacological therapies to treat human fetuses with prenatally diagnosed CDH.
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PMID:Prenatal hormonal therapy improves pulmonary compliance in the nitrofen-induced CDH rat model. 870 26

The lungs of patients born with severe congenital diaphragmatic hernia (CDH) are biochemically and morphologically immature. Because antenatal glucocorticoid therapy can accelerate pulmonary maturation in premature neonates who have respiratory distress syndrome, we hypothesized that it may correct the pulmonary biochemical and morphological immaturity associated with CDH. We showed in previous experimental studies that antenatal low-dose dexamethasone improved the biochemical and morphological parameters of pulmonary immaturity in rats that had severe CDH. Somatic and pulmonary growth were inhibited with high doses of dexamethasone. In the present study, we examined the effects of antenatal low-dose dexamethasone and thyrotropin-releasing hormone (TRH), alone or in combination, on the pulmonary maturation in CDH. Combined antenatal low-dose dexamethasone and TRH significantly reduced mean lung glycogen concentration (P = .001), and increased mean disaturated phosphatidylcholine content (P < .005) to better than that observed with either therapy alone, without changing mean body or lung weight. Combined TRH and low-dose glucocorticoid as an antenatal therapy may reduce the morbidity and mortality of CDH.
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PMID:Combined antenatal thyrotropin-releasing hormone and low-dose glucocorticoid therapy improves the pulmonary biochemical immaturity in congenital diaphragmatic hernia. 817 20

The high mortality of congenital diaphragmatic hernia (CDH) is due to associated pulmonary hypoplasia, which resembles that seen in premature newborns with respiratory distress syndrome (RDS). By use of successful therapies extrapolated from RDS, quantitative stereologic morphometry techniques were applied to evaluate pulmonary development following prenatal hormonal therapy in rats with nitrofen-induced CDH. Antenatal hormonal therapy was administered on Days 18.5 and 19.5 prior to delivery on Day 21.5 (term = Day 22), using dexamethasone (Dex), thyrotropin-releasing hormone (TRH), Dex-TRH, or normal saline (NS) as vehicle control. Lungs from CDH rats (n = 5) and non-nitrofen-fed controls (n = 5) were studied, and 10 morphometric airspace parameters were determined by point counting 18-30 fields/lung/animal. Indices of maturation, including total internal surface area (SA), airspace volume fractions (V(Valv)), duct fractions (V(Vducts)), and radial alveolar count (RAC), were improved by Dex and Dex-TRH compared with NS-CDH controls (P = 0.0001), as were five other morphometric airspace parameters (P < 0.05). Strikingly, Dex and Dex-TRH treatment corrected average airspace volume (AAV) and the volume fraction of air-conducting elements (V(Vducts)) toward normal values seen in non-nitrofen-fed control animals. TRH therapy alone had minimal beneficial effects. Prenatal steroid +/- TRH thus improved multiple morphometric parameters of lung maturity in CDH rats, supporting the potential use of in utero hormonal therapy to treat humans with antenatally diagnosed CDH.
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PMID:Prenatal hormonal therapy improves pulmonary morphology in rats with congenital diaphragmatic hernia. 889 5

Prenatal administration of dexamethasone (Dex) and thyrotropin-releasing hormone (TRH) synergistically enhances lung maturity, but TRH suppresses the antioxidant enzyme activity. Prenatal hormonal therapy improves alveolar surfactant content and lung compliance in rats with congenital diaphragmatic hernia (CDH). In full term neonatal rats with CDH we studied the effects of prenatal Dex or Dex+TRH on antioxidant enzyme activity at birth, on survival, and on lung morphometry after 4 h of ventilation with 100% O2. CDH was induced by administration of 2,4-dichlorophenyl-p-nitro-phenylether (Nitrofen) on gestational day 10. Dex+TRH-treated CDH rats had lower activity of glutathione reductase after birth than did sham-treated CDH pups. Dex-treated and sham-treated pups had similar antioxidant enzyme activity. Hormonal treatment did not change survival during ventilation. The average airspace volume increased in Dex-treated CDH pups after ventilation, with a small synergistic effect after addition of TRH. On the basis of our findings, we speculate that prenatal administration of Dex is the best choice to improve lung maturity and airspace volume in CDH patients.
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PMID:Prenatal hormones alter antioxidant enzymes and lung histology in rats with congenital diaphragmatic hernia. 922 4