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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper examines the amounts of tensoactive phospholipids in the lung tissue of rat fetuses treated with Nitrofen (TOK) and in control animals. The herbicide led to congenital diaphragmatic hernia (CDH) in some fetuses and to pulmonary hypoplasia (PH) in all. The amounts of phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) per gram of fresh lung tissue were significantly increased in comparison with the control animals, those of phosphatidylserine (PS) and sphingomyelin (SM) were also increased, but not significantly. Fetuses with HP alone had intermediate values. These findings are in agreement with our previous demonstration of an excess of type II pneumocytes in this model, and point to the existence of some trouble of the secretion or release of surfactant in it; although they do no clarify whether the amount of alveolar surfactant is in fact decreased.
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PMID:[Pulmonary surfactant in experimental congenital diaphragmatic hernia]. 129 31

This paper explores whether there is a correlation between kidney and lung growths in an experimental model of congenital diaphragmatic hernia (CDH) induced by intragastric administration of Nitrofen (115 mg/kg) in olive oil on time-dated pregnant Wistar rats at the 9th day of gestation. For comparison we used pregnant rats treated with olive oil alone. Twenty-nine normal fetuses from 3 control rats and 24 left CDH fetuses from 6 Nitrofen rats were studied. Fetal (3.6 +/- 0.8 v 4.9 +/- 0.4 g, P < .001) and total lung (2% +/- 0.5% v 2.6% +/- 0.3% of body weight, P < .001) weights were significantly decreased in animals with CDH. Kidneys were also smaller in CDH animals although not significantly (0.7% +/- 0.1% v 0.8% +/- 0.1% of body weight, P = .05) and were also histologically immature. Regression of kidney weight on body weight for both groups yielded regression lines that were identical at analysis of covariance and all data points from the CDH group were within the control group 95% confidence limits. After converting raw data into lung/body and kidney/body weight ratios, no inverse correlation suggesting a feedback mechanism of growth regulation between both organs could be found. Since nitrofen acts through modifications of the thyroid hormone status in both dam and fetus, altered maturation of several organs should be expected although some of them, like the lung, are the leading targets. The present CDH rodent model is probably different from the human malformation in spite of the striking anatomic similarities between them.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The kidney in the fetal rat model of congenital diaphragmatic hernia induced by nitrofen. 140 22

We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage.
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PMID:Nitrofen-induced diaphragmatic hernias in rats: pulmonary antioxidant enzyme activities. 143 89

Aiming at better understanding the mechanisms of malformation and the pathophysiology of congenital diaphragmatic hernia (CDH) and the pulmonary hypoplasia (PH) associated to it we have developed an experimental model in the Wistar rat fetus according to the following design: Three time-dated pregnant rats had 1 ml of olive oil instilled into the stomach at the 9 1/2 day of gestation (control group) and six more were treated with 115 mg/kg of Nitrofen in olive oil (experimental group). After Cesarean section on the 21st day we recovered 29 normal fetuses from the control and 41 fetuses from the experimental groups. Seventeen of these did not have diaphragmatic defects whereas the remaining 24 had left CDH. Fetuses from treated rats were significantly smaller than control ones and those bearing CDH were even smaller than their littermates. Total wet lung weight was significantly smaller in both subgroups of the experimental group. Histologic studies revealed that: 1) There were some variations in the degree of pulmonary hypoplasia in fetuses with CDH probably related to the size of the defect. 2) The main differences in maturation between lungs in control and experimental groups were in the tubulo-acinar structure. We describe the ultrastructure in both groups. This study recalls that some teratogens may be implicated in the pathogenesis of CDH, and also that PH, which was also present in treated fetuses without CDH, could be the cause rather than the consequence of CDH. In that case, our current therapeutic aims should be reviewed.
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PMID:[Experimental congenital diaphragmatic hernia with pulmonary hypoplasia in a rat model]. 156 44

Experiments to induce congenital diaphragmatic hernia (CDH) in rats, by means of administering a single dose of 2,4-dichlorophenyl-P-nitrophenyl (Nitrofen) on the 10th day of gestation, are reported here. Previously, congenital diaphragmatic hernia has been induced in sheep late in fetal development, and in mice early in gestation. The rat model, including a control group, was used to evaluate lung development and the presence of lung hypoplasia by morphometrical analysis. It was found that the single dose of Nitrofen, given 5 days before the normal closure of the diaphragm in the rat, leads to a high incidence of diaphragmatic hernia, mainly on the right side, and highly abnormal lung development (hypoplasia) comparable to the human situation. Both the lung weight/body weight index as well as the radial alveolar count were significantly lower in animals with CDH (P less than .05). This animal model offers a good opportunity to study abnormal lung development in relation to ventilatory capacity and pulmonary vascular reactivity.
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PMID:Experimentally induced congenital diaphragmatic hernia in rats. 232 58

In embryological terms, pathogenesis of congenital diaphragmatic hernia (CDH) associated with pulmonary hypoplasia is still unclear. However, it is known since 1971 that Nitrofen (2,4-dichloro-phenyl-p-nitrophenyl ether) can induce anatomical malformations in rats including diaphragmatic hernias. On order to establish an animal model of the embryogenesis of CDH, the effect of Nitrofen on the developing diaphragm was studied. Thirty-three pregnant female rats were exposed to Nitrofen. Five unexposed pregnant rats served as controls. In the first set of experiments, single doses of Nitrofen were given between the 9th and 13th day of pregnancy. In the second set of experiments, dosages of 50, 100, and 150 mg per animal were given on day 11 of pregnancy only. Postnatally the litters (469 newborn rats) were dissected to record the incidence of diaphragmatic malformations. The results were: (1) most hernias occurred after administration of 100 mg Nitrofen on day 9 (42%) and 11 (59%); (2) left-sided hernias were observed only after exposure to Nitrofen on day 9; (3) after exposure on day 10 or later all hernias were on the right side; and (4) Fifty-nine percent of the newborn rats exposed on day 11 had CDH. These results show that this model is suitable for further embryological investigations on the development of CDH.
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PMID:Nitrofen-induced diaphragmatic hernias in rats: an animal model. 240 39

The purpose of this study was to determine whether hypoplasia of the lung bud might be responsible for cases of congenital diaphragmatic hernia (CDH). The lung bud normally develops in close association with the posthepatic mesenchymal plate ( PHMP ). The PHMP appears dorsal to the liver or on the ventral aspect of the pleuroperitoneal canal when the lung bud enters the pleuroperitoneal canal. Later, the PHMP grows to join the costal mesenchymal tissue via the pleuroperitoneal fold, thereby forming the primitive diaphragm. The present study found that the PHMP plays a cardinal role in the development of the diaphragm and that hypoplasia of the lung bud preceded hypoplasia of the PHMP in mice with CDH produced by the administration of Nitrofen to their pregnant mothers. This, along with findings related to the development of the phrenic nerve, makes it possible that pulmonary hypoplasia is a causal factor in the origin of congenital diaphragmatic hernia.
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PMID:Experimental study on embryogenesis of congenital diaphragmatic hernia. 674 52

Nitric oxide (NO) produced by the enzyme nitric oxide synthase (NOS) is critically involved in the cardiopulmonary transition from fetal to neonatal life. In congenital diaphragmatic hernia (CDH) this transition often does not occur normally, resulting in persistent pulmonary hypertension of the newborn (PPHN). We sought to determine if pulmonary NOS expression is altered in a rat model of CDH induced by maternal ingestion of the herbicide 2,4-dichlorophenyl-p-nitrophenyl ether (Nitrofen) on day 9 of gestation (term = 22 days). Sixty-three percent of Nitrofen-exposed fetuses developed CDH. Endothelial NOS (eNOS) and neuronal NOS (nNOS) protein expression were assessed in ipsilateral CDH lungs and in control lungs (Nitrofen-treated, no hernia) at 20 d gestation using immunoblot analyses. eNOS and nNOS have been immunohistochemically localized to rat pulmonary endothelium and bronchiolar epithelium, respectively, and we have previously demonstrated that their expression normally increases during late gestation to be maximal near term. eNOS protein expression was decreased in CDH versus control lung (58 +/- 6 versus 100 +/- 6% of control, n = 5). In contrast, nNOS protein abundance was similar. Factor VIII-associated antigen expression was comparable in CDH and control lung, indicating that the change in eNOS is not related to differences in endothelial cell density. eNOS mRNA abundance was evaluated in semiquantitative reverse transcription-polymerase chain reaction assays. Paralleling the decline in eNOS protein expression, eNOS mRNA was decreased in CDH versus control lung (22 +/- 8 versus 100 +/- 31% of control, n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary endothelial nitric oxide synthase gene expression is decreased in a rat model of congenital diaphragmatic hernia. 757 5

Lung hypoplasia (LH) and pulmonary hypertension are responsible for the high mortality rate in congenital diaphragmatic hernia (CDH) patients. Angiotensin-converting enzyme (ACE) plays a role in the regulation of pulmonary vascular resistance in the postnatal period and might be involved in the development of pulmonary hypertension of the newborn. A study was made of the development of ACE activity spectrophotometrically in a rat model of LH and CDH. It was previously shown that the lungs in this model are hypoplastic and the muscularization of the pulmonary vascular bed is increased. CDH was induced in fetal rats by oral administration of 115 mg/kg Nitrofen to the mother on day 10.5 of pregnancy. Fetuses were delivered by hysterotomy on days 19, 20, 21, and 22. Nitrofen-exposed rats showed significantly lower lung weights and not statistically significant lower total ACE activities than in controls. ACE activity expressed per milligram lung wet weight and per milligram protein was significantly increased compared to controls. ACE converts angiotensin I to the vasoconstrictor angiotensin II, and it inactivates the vasodilator bradykinin. Increased ACE activity may therefore contribute to pulmonary hypertension. Whether ACE and angiotensin II levels are increased in human newborns with a diaphragmatic defect and whether they contribute to the development of persistent pulmonary hypertension has not been studied up till now.
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PMID:Angiotensin-converting enzyme activity is increased in lungs of rats with pulmonary hypoplasia and congenital diaphragmatic hernia. 772 78

Lung hypoplasia and persistent pulmonary hypertension are the principal causes of high mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Amine- and peptide-producing pulmonary neuroendocrine cells (PNEC), widely distributed throughout the airway mucosa, are thought to play an important role in both pulmonary development and regulation of pulmonary vascular tone. Furthermore, recent studies show increased levels of calcitonin gene-related peptide (CGRP), a pulmonary vasodilator produced by PNEC, during chronic hypoxia. The article reports data on morphometric analysis of CGRP immunoreactive PNEC clusters (neuroepithelial bodies, NEB) in a rat model of CDH. CDH was induced in neonatal Sprague Dawley rats by oral administration of 2,4-dichloro-phenyl-p-nitrophenylether (Nitrofen; Rohm Haas, Philadelphia, PA) to the mother at 10 days of gestation. Sections of lungs from term neonatal rats with and without CDH and controls were immunostained for CGRP (marker of NEB) with specific antibody against rat CGRP. NEB size and number of NEB/area of lung were assessed using a semiautomatic image analysis system. In lungs of neonatal rats with CDH, the number of NEB per surface area of lung parenchyma was significantly increased compared with the age-matched controls. Although the mean size of NEB was larger in CDH, the differences were not significant. This is the first study of PNEC in CDH. Whether the phenomenon observed in this study results in altered NEB function including imbalance in vasoactive mediators requires further studies, especially in the human being.
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PMID:Pulmonary neuroendocrine cells in neonatal rats with congenital diaphragmatic hernia. 776 Feb 32


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