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)

The etiology of congenital diaphragmatic hernia (CDH) is not yet known. Studies in the literature from 1941 have reported that nutritional deficiency of vitamin A during pregnancy could lead to CDH, associated or not with other malformations in young rats. More recently, possible correlations between expression patterns of cellular retinoid-binding protein and retinoic-acid receptors and morphologic effects of vitamin A deficiency have been suggested. The purpose of this study was to verify in human newborns the possible link between vitamin A deficiency and CDH previously observed in experimental animals. Blood samples were obtained during the first hours after birth from 11 term CDH newborns and 11 healthy controls matched for gestational age, and also from 7 mothers in each group, for a total of 7 newborn-mother pairs of matched CDH-controls. Plasma retinol was measured by high-performance liquid chromatography and retinol-binding protein (RBP) by nephelometry. In the 11 matched CDH-control newborns, plasma retinol and RBP levels in CDH newborns were 50% less than control values (P< 0.0002 and <0.006, respectively); in contrast, retinol levels in CDH mothers were significantly higher than those of control mothers (P < 0.005). The observation that the plasma concentrations of retinol and RBP are low in infants with CDH relative to controls may be clinically very relevant and may help to elucidate the mechanism of development of this congenital anomaly.
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PMID:Retinol status of newborn infants with congenital diaphragmatic hernia. 979 71

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Pulmonary hypoplasia often limits survival. Vitamin A (Vit A) is an important signal for lung growth. We hypothesized that antenatal treatment with Vit A would stimulate lung growth and decrease mortality in experimental CDH induced in rats by ingestion of the herbicide nitrofen (2, 4-dichlorophenyl-p-nitrophenyl ether). Nitrofen was administered to pregnant rats on day 12 of gestation (term 22 days). Rats were assigned to five groups: three groups received one dose of oral antenatal Vit A (15,000 IU) before (day 10), concomitant with (day 12), or after (day 14) nitrofen administration; one group received only nitrofen; and a control group received vehicle (olive oil). The incidence of CDH was markedly lower in all groups receiving Vit A (day 10, 44%; day 12, 20%; and day 14, 40%) compared with the nitrofen-treated group (84%; P < 0.05). The 72-h survival was higher in all 3 Vit A-treated groups (day 10, 40%; day 12, 58%; and day 14, 70%) compared with the nitrofen-treated group (16%; P < 0.05). Lung-to-body weight ratio and radial saccular count were significantly increased by Vit A. Antenatal treatment with Vit A lowers the incidence and severity of experimental CDH and increases lung growth and maturation.
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PMID:Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats. 1044 37

BACKGROUND: There have been few articles about bariatric surgery for morbidly obese children. Nevertheless, children who suffer clinically severe obesity also suffer poor social acceptance and an inability to participate in sports or other life activities. Since 1983 the author has performed vertical banded gastroplasty (VBG), Roux-en-Y gastric bypass (RYGBP), or biliopancreatic diversion (BPD) on 22 children, ages 8 - 18 years. METHODS: This was a retrospective review of 22 children, 11 with sleep apnea and 11 without sleep apnea. There were nine males and 13 females. The procedures were VBG-5; RYGBP-14; and BPD-4. RESULTS: There were no operative deaths, infections, or other serious immediate complications. Body mass index (BMI) in those with sleep apnea decreased from a mean of 67.8 preoperatively to 46.5 kg/m(2) at an average follow-up of 32 months. Likewise, for those without sleep apnea, BMI decreased from 56.4 preoperatively to 35.5 kg/m(2) at an average follow-up of 50 months. All patients with sleep apnea had this condition resolve with adequate weight loss. Furthermore, these patients have been able to stay awake in school and have made better grades. Postoperative complications included protein deficiency in three BPD patients, and Vitamin A and D deficiency, folic acid deficiency, gallstones, kidney stones, postoperative laryngeal edema, and incisional hernia in one patient each. There were two late deaths; one at 15 months and one at 3.5 years postoperatively. CONCLUSIONS: Clinically severely obese children can safely undergo bariatric operations usually offered to adults. Furthermore, most patients have sustained significant weight loss. Those patients with sleep apnea have had resolution of their sleep apnea. Complications can be minimized with adequate vitamin, mineral, and trace element supplementation. Long-term results are not yet known.
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PMID:Obesity Surgery in Children. 1073 12

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Besides pulmonary hypoplasia, the pathophysiology of CDH also includes surfactant deficiency. Vitamin A (vit A) is important for various aspects of lung development. We hypothesized that antenatal treatment with vit A would stimulate lung surfactant synthesis in experimental CDH induced in rats by maternal ingestion of the herbicide nitrofen (2,4-dichloro-phenyl-p-nitrophenyl-ether) on Day 12. Fetuses were assigned to six experimental groups: (1) controls from rats that received olive oil, the vehicle; (2) fetuses from rats that received olive oil on Day 12 and vit A orally (15,000 IU) on Day 14; (3) nitrofen (N)-exposed fetuses without diaphragmatic hernia (N/no DH); (4) N/no DH from rats given vit A on Day 14; (5 ) nitrofen-exposed fetuses with DH (N/+DH); (6) N/+DH from rats given vit A on Day 14. Fetuses were delivered by C-section at Day 21. Lung DNA content was lowered in the nitrofen group as compared with the controls group, but increased by subsequent vit A treatment. Lung surfactant disaturated phosphatidylcholine was reduced in the N/+DH group and restored to control level by vit A. The expression level of surfactant proteins (SP) -A and -C was decreased in vit A-treated control rats and in nitrofen-exposed fetuses with or without DH. Vit A restored SP-A and -C mRNA expression to control levels in N/+DH. SP-B expression was lowered in N/no DH and increased by vit A in this group. The proportion of type II cells assessed by SP-B immunolabeling was lowered in N/+DH and restored by vit A treatment. We conclude that antenatal treatment with vit A restores lung maturation in nitrofen-induced hypoplastic lungs with CDH. These findings point out vit A as a potential therapeutical agent for correcting surfactant deficiency in CDH.
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PMID:Restoring effects of vitamin A on surfactant synthesis in nitrofen-induced congenital diaphragmatic hernia in rats. 1158 1

Vitamin A (vit A) alleviates the effects of nitrofen in exposed rat pups. The present study examines the effects of early exposure to vitamin A on the neural-crest-related cardiovascular, thymic, parathyroid, and thyroid malformations previously reported in the rat model of congenital diaphragmatic hernia (CDH). Pregnant rats were exposed on gestational day 9.5 to 100 mg 2-4-dichlorophenyl-p-nitrophenyl ether (nitrofen) alone or followed by 15,000 IU vit A. Controls were treated only with oil or oil + vit A. The fetuses were recovered near term and diaphragmatic, lung, heart, and thymic malformations were sought after dissection. The parathyroids and thyroid were histologically investigated. The hearts were also examined for protein, DNA, and proportion of proliferating cells. None of the control fetuses had malformations, whereas 41% of nitrofen and 27% of nitrofen + vit A fetuses had CDH. Anomalies of the heart outflow tract and pharyngeal arteries were seen in 64% and 43%, respectively, in both groups. Heart and thymic hypoplasia, which were severe in the nitrofen group with significant decreases of total DNA and percent proliferating cells, were significantly improved in the nitrofen + vit A group. The hypoplastic thymus was malformed in 53% and 27% of fetuses, respectively, and the parathyroids were abnormal in 48% and 35%, respectively. Only minimal anomalies of the thyroid were found. The significant improvement of heart and thymic hypoplasia associated with vit A was not seen for the other variables studied, but there was a trend in this direction for all of them. Vit A definitely improved heart hypoplasia induced by nitrofen by stimulating myogenesis. It also improved thymic hypoplasia, but had limited beneficial effects on malformations of the cardiac outflow tract and pharyngeal derivatives that accompany CDH in rats exposed to nitrofen.
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PMID:Effects of vitamin A on malformations of neural-crest-controlled organs induced by nitrofen in rats. 1247 74

Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality and morbidity due to pulmonary hypoplasia and pulmonary hypertension. Antenatal interventions have been developed in an attempt to reduce the unacceptable mortality rate of CDH. The pathogenesis of pulmonary hypoplasia is not fully understood. It is not clear whether the increase of lung growth would be necessary for diaphragmatic closure. Vitamin A is important for various aspects of lung development. Therefore, the aim of this study was to examine whether antenatal treatment with vitamin A can increase lung growth and reduce the incidence of CDH in a nitrofen-treated rat model. The animals were randomly assigned to four groups: control, vitamin A, nitrofen, and nitrofen/vitamin A (NIP/Vit A). The incidence of CDH in the NIP/Vit A group (54%) was markedly lower than that in the nitrofen-treated group (85%). Although lung weight was decreased in the nitrofen-treated and NIP/vitamin A groups, the fetal lung weight-to-body weight ratio was slightly increased in the NIP/vitamin A group, compared to the nitrofen-treated group. The mRNA levels of lung surfactant proteins were decreased in the NIP/vitamin A group. We conclude that antenatal treatment with vitamin A reduced the incidence of CDH without lung maturation in the nitrofen-induced rat model.
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PMID:Differential effects of vitamin A on fetal lung growth and diaphragmatic formation in nitrofen-induced rat model. 1570 48

Rats with experimental congenital diaphragmatic hernia (CDH) have heart hypoplasia and conotruncal and great vessel malformations that are likely related to disturbed neural crest developmental control. Neural crest cells communicate through intercellular gap junctions whose main protein is Connexin 43 (Cx43). The migration and participation of neural crest cells in heart development is likely influenced by this protein which might be also directly involved in myocardial development. Vitamin A is beneficial for heart hypoplasia in CDH rats. The aims of this study were to examine the status of Cx43 in the heart of embryonal rats exposed to nitrofen and to assess if vitamin A reverts these effects. Pregnant rats received either 100 mg nitrofen or olive oil on E9.5. Each group was divided into two subgroups according to the subsequent treatment with intragastric vitamin A (15,000 i.u.) or vehicle on E10.5 and E11.5. The pups were recovered on E13, E15, and E21 and the hearts were dissected out and pooled. Cx43 mRNA expression was determined by quantitative real-time PCR. Comparisons among groups were made with ANOVA and Bonferroni post hoc tests with a threshold of significance of P<0.05. In control rats Cx43 mRNA was minimally expressed on E13 and E15 and fully expressed on E21. Nitrofen significantly increased Cx43 mRNA on E15. Additional treatment with vitamin A tended to moderate this increase on E15. Cx43 was overexpressed in the hearts of nitrofen-exposed embryonal rats on day E15 of gestation. Vitamin A tended to normalize this expression. The mechanism of action of Cx43 deserves further investigation.
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PMID:Expression of Connexin 43 in the hearts of rat embryos exposed to nitrofen and effects of vitamin A on it. 1629 52

The effect of 4 days total starvation (water only) in five normal subjects on the circulating concentrations of various proteins was studied. Changes in plasma albumin and total protein concentrations were compared with those of six patients undergoing elective abdominal surgery with partial starvation and six patients undergoing orthopaedic surgery with adequate feeding - (0.126-0.146 MJ/kg/day and 1.2-1.4 g protein/kg/day). In a companion study hand grip strength was measured daily in ten normal subjects during starvation and in 18 patients undergoing surgery for hernia repair (n = 6), cholecystectomy (n = 6) and major abdominal surgery (n = 6). Starvation produced marked reductions (approximately 30%) in the circulating concentrations of retinol binding protein and prealbumin but did not significantly affect the plasma concentration of immunoglobulins (IgG, IgA, IgM) acute phase reactants (orosomucoid, haptoglobin, alpha(1) antitrypsin), albumin and total protein. On the other hand both types of elective surgery produced significant reductions in plasma albumin and total protein concentrations irrespective of feeding. Grip strength was not significantly altered by four days of starvation but surgery produced a temporary reduction in grip strength, the extent and duration of which was related to the severity of operation. This study helps to separate the effect of surgery and starvation on hand dynamometry and circulating protein concentrations and indicates their limitations as indicators of nutritional state.
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PMID:Effect of starvation and elective surgery on hand dynamometry and circulating concentration of various proteins. 1682 52

Retinoids are a group of molecules derived from vitamin A, which play an important role in lung development. Within the cell, retinol can either be oxidized to retinal or esterified to retinyl esters by lecithin : retinol acyltransferase (LRAT) for storage. Retinal is then oxidized to an active metabolite of vitamin A, retinoic acid (RA) by retinal dehydrogenase (RALDH). RA is the active metabolite of vitamin A. Cyp26 (a1,b1, and c1), which is a member of the cytochrome P450 family, acts by reducing the activity of RA. Cyp26 type b1 is the predominant subtype expressed in the murine lung. Several studies have suggested that nitrofen may interfere with the retinoid pathway resulting in congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia. Recently, it was reported that nitrofen may act by inhibiting RALDH2. The aim of this study was to examine the pulmonary expression of Cyp26b1, LRAT, and RALDH2, the key enzymes involved in the synthesis of RA, in order to understand the mechanisms underlying pulmonary hypoplasia in the nitrofen CDH model. Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9 of gestation (D9). Fetal lungs were harvested at D15, D17, D19, and D21. D17, D19, and D21 lungs were divided into three groups: control, nitrofen without CDH and nitrofen with CDH, whereas D15 lungs were divided into only two groups; control and nitrofen as the diaphragm is not fully formed yet at this stage. Real- time PCR was performed to evaluate the relative level of Cyp26b1, LRAT, and RALDH2 expression in the lung. Relative levels of Cyp26b1 mRNA were significantly decreased in the lungs of nitrofen with CDH (D17;0.19 +/- 0.09, D19;0.70 +/- 0.20, D21;0.40 +/- 0.36) and nitrofen without CDH (D17;0.14 +/- 0.06, D19;0.54 +/- 0.42, D21;0.51 +/- 0.56) compared to controls (D17;0.35 +/- 0.16, D19;1.15 +/- 0.48, D21;1.28 +/- 0.78) (P < 0.05). LRAT expression was also significantly decreased in nitrofen with CDH (D17; 19.3 +/- 7.8, D19; 4.3 +/- 1.1, D21; 3.3 +/- 1.6) and nitrofen without CDH (D17; 21.2 +/- 11.1, D19; 4.5 +/- 3.6, D21; 4.1 +/- 1.6) compared to controls (D17; 153.7 +/- 29.8, D19; 26.8 +/- 16.8 D21; 10.1 +/- 3.8) (P < 0.05). There was no significant difference in the relative levels of Cyp26b1 and LRAT between nitrofen with CDH and nitrofen without CDH. There were no significant differences in RALDH2 expression among the groups at any stages. Down-regulation of Cryp26b1 and LRAT demonstrates that RA content is decreased in nitrofen induced hypoplastic lungs compared to controls. The finding that RALDH2 expression in the hypoplastic lung is not altered suggests that nitrofen may act by interfering with the retinoid metabolism during the early stage of the retinoid signaling pathway.
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PMID:Altered regulation of retinoic acid synthesis in nitrofen-induced hypoplastic lung. 1720 25

Matthew-Wood, Spear, PDAC or MCOPS9 syndrome are alternative names used to refer to combinations of microphthalmia/anophthalmia, malformative cardiac defects, pulmonary dysgenesis, and diaphragmatic hernia. Recently, mutations in STRA6, encoding a membrane receptor for vitamin A-bearing plasma retinol binding protein, have been identified in such patients. We performed STRA6 molecular analysis in three fetuses and one child diagnosed with Matthew-Wood syndrome and in three siblings where two adult living brothers are affected with combinations of clinical anophthalmia, tetralogy of Fallot, and mental retardation. Among these patients, six novel mutations were identified, bringing the current total of known STRA6 mutations to seventeen. We extensively reviewed clinical data pertaining to all twenty-one reported patients with STRA6 mutations (the seven of this report and fourteen described elsewhere) and discuss additional features that may be part of the syndrome. The clinical spectrum associated with STRA6 deficiency is even more variable than initially described.
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PMID:Phenotypic spectrum of STRA6 mutations: from Matthew-Wood syndrome to non-lethal anophthalmia. 1930 93


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