Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats

1999 ◽  
Vol 277 (2) ◽  
pp. L423-L429 ◽  
Author(s):  
Bernard Thébaud ◽  
Dick Tibboel ◽  
Caroline Rambaud ◽  
Jean-Christophe Mercier ◽  
Jacques R. Bourbon ◽  
...  
Keyword(s):  
Vitamin A ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Weight Ratio ◽  
Treated Group ◽  
Control Group ◽  
Lung Growth ◽  
Body Weight Ratio ◽  
Pregnant Rats ◽  
Antenatal Treatment

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.

Fetal tracheal occlusion in the rat model of nitrofen-induced congenital diaphragmatic hernia

1999 ◽  
Vol 87 (2) ◽  
pp. 769-775 ◽  
Author(s):  
Yoshihiro Kitano ◽  
Paul Davies ◽  
Daniel von Allmen ◽  
N. Scott Adzick ◽  
Alan W. Flake
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Rat Model ◽  
Weight Ratio ◽  
Lung Parenchyma ◽  
Lung Hypoplasia ◽  
Lung Growth ◽  
Lung Weight ◽  
Pregnant Rats ◽  
Tracheal Occlusion

Prenatal tracheal occlusion (TO) consistently accelerates lung growth in the sheep model of congenital diaphragmatic hernia (CDH). However, significant variability in lung growth has been observed in early clinical trials of TO. We hypothesized that lung hypoplasia created at relatively late stages of lung development may not be equivalent to human CDH-induced lung hypoplasia, which begins early in gestation. To test this hypothesis, we performed TO in the rat model of nitrofen-induced CDH. Left-sided CDH was induced by administering 100 mg of nitrofen to timed pregnant rats on day 9 of gestation. On day 19 of gestation, four to five fetuses per dam underwent surgical ligation of the trachea. At death ( day 21.5), lungs from non-CDH (non-CDH group), left-CDH (CDH group), and trachea-occluded left-CDH fetuses (CDH-TO group) were harvested and compared by weight, DNA and protein content, and stereological morphometry. Wet and dry lung weight-to-body weight ratio, total lung DNA and protein contents, the volume of lung parenchyma, and the total saccular surface area of the CDH-TO group were significantly increased relative to the CDH group and were either greater than or comparable to the non-CDH controls. We conclude that TO accelerates lung growth and increases lung parenchyma in an early-onset model of CDH-induced lung hypoplasia.

Lung Pathology in Patients with Congenital Diaphragmatic Hernia Treated with Fetal Surgical Intervention, Including Tracheal Occlusion

2003 ◽  
Vol 6 (6) ◽  
pp. 536-546 ◽  
Author(s):  
Amy E. Heerema ◽  
Joseph T. Rabban ◽  
Roman M. Sydorak ◽  
Micheal R. Harrison ◽  
Kirk D. Jones
Keyword(s):  
Body Weight ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Pulmonary Hypoplasia ◽  
Weight Ratio ◽  
Lung Pathology ◽  
Body Weight Ratio ◽  
Fetal Intervention ◽  
Tracheal Occlusion ◽  
Significant Difference

Fetal intervention for congenital diaphragmatic hernia was developed to lessen the high morbidity and mortality of pulmonary hypoplasia. Lung pathology and morphometry in patients treated with fetal intervention have not been described. We report clinical and autopsy findings, as well as basic lung morphometry in 16 cases of congenital diaphragmatic hernia with fetal intervention (12 cases tracheal occlusion; 4 cases hernia repair), and 19 cases of congenital diaphragmatic hernia without fetal intervention. All patients who underwent fetal intervention were born premature. Lung enlargement with increased lung-to-body weight ratio was observed with fetal tracheal occlusion, accompanied by lower than normal radial alveolar counts and increased alveolar size. Patients treated with tracheal occlusion also had early alveolar development (at 29.8, 30.6, and 30.9 wk postconceptual age) as well as mucous fluid pooling in airways and alveoli. All cases showed severe alveolar septal widening, more extensive in patients without fetal intervention. When grouped by postconceptual age, no statistically significant difference was found between patients with and without fetal intervention with respect to lung-to-body weight ratio, radial alveolar count, mean alveolar length, and relative arteriolar media thickness. Lung enlargement has been observed with fetal tracheal occlusion sonographically; our studies suggest that this is due in part to emphysema and mucous fluid pooling. The lung remains abnormal with low radial alveolar counts and increased alveolar size. Tracheal occlusion did not prevent development of lung pathology associated with pulmonary hypoplasia.

scholarly journals Maternal dietary intake of vitamin A during pregnancy was inversely associated with congenital diaphragmatic hernia: the Japan Environment and Children’s Study

2019 ◽  
Vol 122 (11) ◽  
pp. 1295-1302 ◽  
Author(s):  
Takehiro Michikawa ◽  
Shin Yamazaki ◽  
Makiko Sekiyama ◽  
Tatsuo Kuroda ◽  
Shoji F. Nakayama ◽  
...  
Keyword(s):  
Vitamin A ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Dietary Habits ◽  
Daily Intake ◽  
First Trimester ◽  
Dietary Vitamin ◽  
Birth Cohort Study ◽  
Case Control Studies ◽  
Total Vitamin

AbstractThe pathogenesis of congenital diaphragmatic hernia (CDH) is largely unknown; however, vitamin A seems to play a role in diaphragmatic development. Previous case–control studies reported that maternal dietary vitamin A intake was inversely associated with the risk of CDH. To our knowledge, however, there is no prospective evidence regarding this association. Our aim was to examine whether maternal intake of vitamin A was associated with CDH occurrence. Baseline data, from the Japan nationwide birth cohort study (2011–2014) of 89 658 mothers (mean age at delivery = 31·2 years) who delivered singleton live births, were analysed. We assessed dietary habits using an FFQ focused on the first trimester and estimated the daily intake of total vitamin A (retinol activity equivalents), retinol, provitamin A carotenoids and vegetables. The occurrence of CDH was ascertained from medical records. A total of forty cases of CDH were documented. The adjusted OR of CDH occurrence for the high total vitamin A intake category (median = 468 μg/d) was 0·6 (95 % CI 0·3, 1·2) with reference to the low intake category (230 μg/d). When we restricted to mothers with a prepregnancy BMI of 18·5–24·9 kg/m2, vitamin A intake was inversely associated with the risk of their children being born with CDH (OR 0·5, 95 % CI 0·2, 1·0). Even given the limited number of cases in the study, our findings provide additional evidence to link vitamin A with CDH.

scholarly journals Computed tomography based measurements to evaluate lung density and lung growth after congenital diaphragmatic hernia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Timm Stoll-Dannenhauer ◽  
Gregor Schwab ◽  
Katrin Zahn ◽  
Thomas Schaible ◽  
Lucas Wessel ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Contralateral Side ◽  
Chest Ct ◽  
Control Group ◽  
P Value ◽  
Lung Density ◽  
Ipsilateral Lung ◽  
Contralateral Lung ◽  
Pediatric Chest

AbstractEmphysema-like-change of lung is one aspect of lung morbidity in children after congenital diaphragmatic hernia (CDH). This study aims to evaluate if the extent of reduced lung density can be quantified through pediatric chest CT examinations, if side differences are present and if emphysema-like tissue is more prominent after CDH than in controls. Thirty-seven chest CT scans of CDH patients (mean age 4.5 ± 4.0 years) were analyzed semi-automatically and compared to an age-matched control group. Emphysema-like-change was defined as areas of lung density lower than − 950 HU in percentage (low attenuating volume, LAV). A p-value lower than 0.05 was regarded as statistically significant. Hypoattenuating lung tissue was more frequently present in the ipsilateral lung than the contralateral side (LAV 12.6% vs. 5.7%; p < 0.0001). While neither ipsilateral nor contralateral lung volume differed between CDH and control (p > 0.05), LAV in ipsilateral (p = 0.0002), but not in contralateral lung (p = 0.54), was higher in CDH than control. It is feasible to quantify emphysema-like-change in pediatric patients after CDH. In the ipsilateral lung, low-density areas are much more frequently present both in comparison to contralateral and to controls. Especially the ratio of LAV ipsilateral/contralateral seems promising as a quantitative parameter in the follow-up after CDH.

scholarly journals Effect of nitrofen in the final stages of development of the diaphragm muscle in rats

2013 ◽  
Vol 28 (suppl 1) ◽  
pp. 13-18 ◽  
Author(s):  
Frances Lilian Lanhellas Gonçalves ◽  
Fábio Santana de Oliveira ◽  
Augusto Frederico Schmidt ◽  
Luís Antônio Violin Dias Pereira ◽  
Rodrigo Melo Gallindo ◽  
...  
Keyword(s):  
Body Weight ◽  
Congenital Diaphragmatic Hernia ◽  
Olive Oil ◽  
Diaphragmatic Hernia ◽  
Muscle Fibers ◽  
Diaphragm Muscle ◽  
External Control ◽  
Stages Of Development ◽  
Pregnant Rats ◽  
Histological Staining

PURPOSE: To evaluate the expression of myosin in muscle fibers of the diaphragm in experimental congenital diaphragmatic hernia (CDH). METHODS: Fetuses of pregnant rats were divided into four groups: External Control (EC), composed of non-manipulated rats; Nitrofen, composed of pregnant rats that received 100 mg of nitrofen (2,4-dichloro-4'nitrodiphenyl ether) diluted in olive oil on gestational day (GD) 9.5, whose fetuses developed CDH (N+) or not (N-), and Olive Oil Placebo (OO), composed of pregnant rats that received the oil on the same GD. The fetuses were collected on GD 18.5, 19.5, 20.5 and 21.5 (term = 22 days). We obtained body weight (BW) and photographed the diaphragm area (DA), hernia area (HA) and subsequent calculated the HA/DA ratio in N+ group. Samples of Diaphragm muscle were processed for histological staining with H/E and immunohistochemistry (IHQ) for myosin.} RESULTS: The fetuses of N- and N+ groups had decreased BW and DA compared to EC and OO groups (p <0.001). HA was decreased on GD 18.5 compared to 21.5 (p <0.001) and the HA/DA ratio showed no difference. IHQ showed decreased expression of myosin in nitrofen groups. CONCLUSION: CDH induced by nitrofen model contributes to the understanding of muscularization in the formation of the diaphragm where the myosin expression is decreased.

A study on the safety evaluation of buphrenorphine administered through an autoinjector compared with manual injection using haematological and biochemical variables in rats

2016 ◽  
Vol 36 (9) ◽  
pp. 901-909 ◽  
Author(s):  
D Sheela ◽  
R Vijayaraghavan ◽  
S Senthilkumar
Keyword(s):  
Body Weight ◽  
Research Work ◽  
Safety Evaluation ◽  
Weight Ratio ◽  
The Body ◽  
Control Group ◽  
Body Weight Ratio ◽  
Significant Difference ◽  
Manual Group ◽  
Significant Change

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.

scholarly journals Study the Effects of Methotrexate with and without Vitamin A on Some Biochemical and Histological Parameters in Male Rabbits

2017 ◽  
Vol 11 (1) ◽  
pp. 45-53
Author(s):  
Makarim Q. Al-Lami ◽  
Asmaa I. Sail ◽  
Salah M. Al-Chalabi ◽  
Ferial A. Al-Mahdawi
Keyword(s):  
Vitamin A ◽  
Histological Examination ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Low Density ◽  
Typical Structure ◽  
Histological Changes ◽  
Sinusoidal Dilatation

The present study aims to evaluate the effects of methotrexate (MTX) with and without vitamin A (Vit. A) on some biochemical parameters and histological structure in male rabbits liver. Twenty male rabbits weighing 1250-1480 gm were divided into four equal number groups. The first group was given 2 ml distilled water as control group. The second group was given MTX (20 mg/kg), the third group was given Vit. A (5000 IU), while the fourth group was given MTX (20 mg/kg) +Vit. A (5000 IU) in alternative days. Following four weeks of treatment, lipid profile total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), [low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL)]; in addition to thyroid hormones triiodothyronine (T3) and thyroxin (T4)] and liver enzymes [glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT)] were determined in the serum. Also, the histological examination of liver of all the experimental groups were carried out. The results were revealed that the treatment with MTX caused a significant P≤0.05 increases in TC, HDL, LDL, T4, and GPT when compared with the control group. The treatment with Vit. A did not cause any significant P≥0.05 differences in all the studied parameters. The MTX+Vit. A treated group showed a significant P≤0.05 increases only in GPT compared with the control group; while a significant P≤0.05 decreases was found in TC, HDL, T3, T4, and GOT when compared with the MTX treated group. The histological examination of the liver sections showed that MTX administration caused major histological changes in comparison with the control such as inflammatory cell infiltrations, vascular congestion, sinusoidal dilatation and granular degeneration of hepatocytes. Treatment with Vit. A showed a typical structure in liver tissue. While in MTX+Vit. A group, the histological changes were less severe than those in the MTX treated group; these changes were granular degeneration of hepatocytes and sinusoidal dilatation at low levels. The overall results of this study confirmed that administration of Vit. A decreased the side effects of MTX; this protective effect of Vit. A may have clinical applications in chemotherapy.

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