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https://www.readbyqxmd.com/read/29409619/lung-function-and-pulmonary-artery-blood-flow-following-prenatal-maternal-retinoic-acid-and-imatinib-in-the-nitrofen-model-of-congenital-diaphragmatic-hernia
#1
Carmen Mesas Burgos, Marcus G Davey, John S Riley, Huimin Jia, Alan W Flake, William H Peranteau
BACKGROUND: Lung and pulmonary vascular maldevelopment in congenital diaphragmatic hernia (CDH) results in significant morbidity and mortality. Retinoic acid (RA) and imatinib have been shown to improve pulmonary morphology following prenatal administration in the rat nitrofen-induced CDH model. It remains unclear if these changes translate into improved function. We evaluated the effect of prenatal RA and imatinib on postnatal lung function, structure, and pulmonary artery (PA) blood flow in the rat CDH model...
December 19, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29216632/perturbations-in-endothelial-dysfunction-associated-pathways-in-the-nitrofen-induced-congenital-diaphragmatic-hernia-model
#2
Siqin Zhaorigetu, Henry Bair, Jonathan Lu, Di Jin, Scott D Olson, Matthew T Harting
Although it is well known that nitrofen induces congenital diaphragmatic hernia (CDH), including CDH-associated lung hypoplasia and pulmonary hypertension (PH) in rodents, the mechanism of pathogenesis remains largely unclear. It has been reported that pulmonary artery (PA) endothelial cell (EC) dysfunction contributes to the development of PH in CDH. Thus, we hypothesized that there is significant alteration of endothelial dysfunction-associated proteins in nitrofen-induced CDH PAs. Pregnant SD rats received either nitrofen or olive oil on gestational day 9...
December 8, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/29203958/role-of-catalytic-iron-and-oxidative-stress-in-nitrofen-induced-congenital-diaphragmatic-hernia-and-its-amelioration-by-saireito-tj-114
#3
Shima Hirako, Hiroyuki Tsuda, Fumiya Ito, Yasumasa Okazaki, Tasuku Hirayama, Hideko Nagasawa, Tomoko Nakano, Kenji Imai, Tomomi Kotani, Fumitaka Kikkawa, Shinya Toyokuni
Congenital diaphragmatic hernia (CDH) is a life-threatening neonatal disease that leads to lung hypoplasia and pulmonary hypertension. We recently found that maternal prenatal administration of Saireito (TJ-114) ameliorates fetal CDH in a nitrofen-induced rat model. Here, we studied the role of iron and oxidative stress in neonates of this model and in lung fibroblasts IMR90-SV in association with nitrofen and Saireito. We observed increased immunostaining of 8-hydroxy-2'-deoxyguanosine in the lungs of neonates with CDH, which was ameliorated by maternal Saireito intake...
November 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/29196881/gata-6-expression-is-decreased-in-diaphragmatic-and-pulmonary-mesenchyme-of-fetal-rats-with-nitrofen-induced-congenital-diaphragmatic-hernia
#4
Toshiaki Takahashi, Florian Friedmacher, Julia Zimmer, Prem Puri
PURPOSE: Congenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia are thought to be caused by a malformation of the underlying diaphragmatic and airway mesenchyme. GATA binding protein 6 (Gata-6) is a zinc finger-containing transcription factor that plays a crucial role during diaphragm and lung development. In the primordial diaphragm, Gata-6 expression is restricted to mesenchymal compartments of the pleuroperitoneal folds (PPFs). In addition, Gata-6 is essential for airway branching morphogenesis through upregulation of mesenchymal signaling...
December 2, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/29135495/prenatal-microrna-mir-200b-therapy-improves-nitrofen-induced-pulmonary-hypoplasia-associated-with-congenital-diaphragmatic-hernia
#5
Naghmeh Khoshgoo, Ramin Kholdebarin, Patricia Pereira-Terra, Thomas H Mahood, Landon Falk, Chelsea A Day, Barbara M Iwasiow, Fuqin Zhu, Drew Mulhall, Carly Fraser, Jorge Correia-Pinto, Richard Keijzer
OBJECTIVE: We aimed to evaluate the use of miR-200b as a prenatal transplacental therapy in the nitrofen rat model of abnormal lung development and congenital diaphragmatic hernia (CDH). BACKGROUND: Pulmonary hypoplasia (PH) and pulmonary hypertension determine mortality and morbidity in CDH babies. There is no safe medical prenatal treatment available. We previously discovered that higher miR-200b is associated with better survival in CDH babies. Here, we investigate the role of miR-200b in the nitrofen rat model of PH and CDH and evaluate its use as an in vivo prenatal therapy...
November 13, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/29115963/changes-in-vasoactive-pathways-in-congenital-diaphragmatic-hernia-associated-pulmonary-hypertension-explain-unresponsiveness-to-pharmacotherapy
#6
Daphne S Mous, Marjon J Buscop-van Kempen, Rene M H Wijnen, Dick Tibboel, Robbert J Rottier
BACKGROUND: Patients with congenital diaphragmatic hernia (CDH) have structural and functional different pulmonary vessels, leading to pulmonary hypertension. They often fail to respond to standard vasodilator therapy targeting the major vasoactive pathways, causing a high morbidity and mortality. We analyzed whether the expression of crucial members of these vasoactive pathways could explain the lack of responsiveness to therapy in CDH patients. METHODS: The expression of direct targets of current vasodilator therapy in the endothelin and prostacyclin pathway was analyzed in human lung specimens of control and CDH patients...
November 7, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29079903/anti-oxidants-correct-disturbance-of-redox-enzymes-in-the-hearts-of-rat-fetuses-with-congenital-diaphragmatic-hernia
#7
Rosa Aras-López, L Almeida, V Andreu-Fernández, J Tovar, L Martínez
AIM: To evaluate if the redox system is unbalanced in the hearts of nitrofen-induced congenital diaphragmatic hernia  (CDH) animals and to study the possible preventive effects of two anti-oxidant treatments, apocynin and epigallocatechin-3-gallate (EGCG). METHODS: Adult rats were divided into four groups. Group 1: rats received only vehicle on day E9.5. Group 2: rats received 100 mg nitrofen on day E9.5. Group 3: 1 month before mating rats received apocynin 1...
October 27, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28983729/increased-casr-and-trpc6-pulmonary-vascular-expression-in-the-nitrofen-induced-model-of-congenital-diaphragmatic-hernia
#8
Hiroki Nakamura, Julia Zimmer, Tristan Lim, Prem Puri
AIMS AND OBJECTIVES: The high morbidity and mortality rates in congenital diaphragmatic hernia (CDH) are attributed primarily to severe lung hypoplasia and/or persistent pulmonary hypertension (PPH). PPH in CDH is characterized by abnormal vascular remodeling with thickening of medial and adventitial layers and extension of smooth muscle into previously nonmuscularized arteries. Excessive proliferation of pulmonary arterial smooth muscle cells (PASMC) is an important contributor to the concentric pulmonary arterial remodeling...
October 5, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28701000/decreased-expression-of-integrin-subunits-%C3%AE-3-%C3%AE-6-and-%C3%AE-8-in-the-branching-airway-mesenchyme-of-nitrofen-induced-hypoplastic-lungs
#9
Toshiaki Takahashi, Florian Friedmacher, Julia Zimmer, Prem Puri
No abstract text is available yet for this article.
July 12, 2017: European Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28683507/decreased-rac1-cardiac-expression-in-nitrofen-induced-diaphragmatic-hernia
#10
Hiroki Nakamura, Julia Zimmer, Prem Puri
No abstract text is available yet for this article.
July 6, 2017: European Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28481127/fetal-cardiac-impairment-in-nitrofen-induced-congenital-diaphragmatic-hernia-postmortem-microcomputed-tomography-imaging-study
#11
Gloria Pelizzo, Valeria Calcaterra, Claudio Lombardi, Rossana Bussani, Vanessa Zambelli, Annalisa De Silvestri, Ana Custrin, Manuel Belgrano, Floriana Zennaro
INTRODUCTION: We assessed the post-mortem micro-CT utility to evaluate fetal cardiac impairment in nitrofen-induced congenital diaphragmatic hernia (CDH). METHODS: At 9.5d postconception (dpc), pregnant rats were exposed to nitrofen. At +18 and +21dpc, fetuses were harvested by cesarean section. Postmortem micro-CT and autopsy were performed. Fetuses were assigned to three experimental groups: Control group (C), Nitrofen group (N, exposition to nitrofen without CDH), CDH group...
August 2017: Fetal and Pediatric Pathology
https://www.readbyqxmd.com/read/28363469/down-regulation-of-n-deacetylase-n-sulfotransferase-1-signaling-in-the-developing-diaphragmatic-vasculature-of-nitrofen-induced-congenital-diaphragmatic-hernia
#12
Toshiaki Takahashi, Florian Friedmacher, Julia Zimmer, Prem Puri
BACKGROUND: Congenital diaphragmatic hernia (CDH) has been attributed to various developmental abnormalities of the underlying tissue components. N-deacetylase-N-sulfotransferase-1 (Ndst1) is a strongly expressed biosynthetic enzyme in endothelial cells, which has recently been identified as an important factor during diaphragmatic vascularization. Loss of endothelial Ndst1 has been demonstrated to cause angiogenic defects in the developing diaphragm and disrupt normal diaphragmatic development...
June 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28188034/follistatin-like-1-expression-is-decreased-in-the-alveolar-epithelium-of-hypoplastic-rat-lungs-with-nitrofen-induced-congenital-diaphragmatic-hernia
#13
Toshiaki Takahashi, Julia Zimmer, Florian Friedmacher, Prem Puri
BACKGROUND/PURPOSE: Pulmonary hypoplasia (PH), characterized by incomplete alveolar development, remains a major therapeutic challenge associated with congenital diaphragmatic hernia (CDH). Follistatin-like 1 (Fstl1) is a crucial regulator of alveolar formation and maturation, which is strongly expressed in distal airway epithelium. Fstl1-deficient mice exhibit reduced airspaces, impaired alveolar epithelial cell differentiation, and insufficient production of surfactant proteins similar to PH in human CDH...
May 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/27880037/suppressed-erythropoietin-expression-in-a-nitrofen-induced-congenital-diaphragmatic-hernia
#14
Hajime Takayasu, Koki Hagiwara, Kouji Masumoto
BACKGROUND: Erythropoietin (EPO), an essential stimulator of erythropoiesis produced by the fetal liver, is important both in vascular remodeling and modulation of the endothelial response in the pulmonary vasculature. In addition, EPO guides alveolar development, along with retinoic acid (RA). EPO is a direct target of RA, and the retinoid pathway is altered in the nitrofen-induced congenital diaphragmatic hernia (CDH) model. In the present study, we tested the hypothesis that the synthesis of EPO is suppressed in a rat model of CDH...
May 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/27833996/expression-of-t-box-transcription-factors-2-4-and-5-is-decreased-in-the-branching-airway-mesenchyme-of-nitrofen-induced-hypoplastic-lungs
#15
Toshiaki Takahashi, Florian Friedmacher, Julia Zimmer, Prem Puri
PURPOSE: Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major therapeutic challenge in newborns with congenital diaphragmatic hernia (CDH). T-box transcription factors (Tbx) have been identified as key components of the gene network that regulates fetal lung development. Tbx2, Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung, regulating the process of lung branching morphogenesis. Furthermore, lungs of Tbx2-, Tbx4- and Tbx5-deficient mice are hypoplastic and exhibit decreased lung branching, similar to PH in human CDH...
February 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/27822781/decreased-endoglin-expression-in-the-pulmonary-vasculature-of-nitrofen-induced-congenital-diaphragmatic-hernia-rat-model
#16
Julia Zimmer, Toshiaki Takahashi, Alejandro D Hofmann, Prem Puri
AIM OF THE STUDY: Pulmonary hypertension (PH) remains a therapeutical challenge in neonates born with congenital diaphragmatic hernia (CDH). Endoglin (Eng), an auxiliary receptor component of the transforming growth factor β (TGFβ) signalling pathway, is expressed mainly by endothelial cells and has been found to be involved in angiogenesis and vascular remodelling. Genetic studies have linked TGFβ and Eng mutations to human arterial PH and other cardiovascular syndromes. Eng interacts with the TGFβ receptors 1 and 2 (Tgfβr1, Tgfβr2)...
February 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/27665494/expression-of-prx1-and-tcf4-is-decreased-in-the-diaphragmatic-muscle-connective-tissue-of-nitrofen-induced-congenital-diaphragmatic-hernia
#17
Toshiaki Takahashi, Julia Zimmer, Florian Friedmacher, Prem Puri
BACKGROUND/PURPOSE: Pleuroperitoneal folds (PPFs) are the source of the primordial diaphragm's muscle connective tissue (MCT), and developmental mutations have been shown to result in congenital diaphragmatic hernia (CDH). The protein paired-related homeobox 1 (Prx1) labels migrating PPF cells and stimulates expression of transcription factor 4 (Tcf4), a novel MCT marker that controls morphogenesis of the fetal diaphragm. We hypothesized that diaphragmatic Prx1 and Tcf4 expression is decreased in the nitrofen-induced CDH model...
December 2016: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/27663689/downregulation-of-forkhead-box-f1-gene-expression-in-the-pulmonary-vasculature-of-nitrofen-induced-congenital-diaphragmatic-hernia
#18
J Zimmer, T Takahashi, A D Hofmann, Prem Puri
PURPOSE: High mortality and morbidity in infants born with congenital diaphragmatic hernia (CDH) are attributed to pulmonary hypoplasia and pulmonary hypertension (PH). Forkhead box (Fox) transcription factors are known to be crucial for cell proliferation and homeostasis. FoxF1 is essential for lung morphogenesis, vascular development, and endothelial proliferation. Mutations in FoxF1 and also the Fox family member FoxC2 have been identified in neonates with PH. In human and experimental models of arterial PH, the Fox protein FoxO1 was found to be downregulated...
December 2016: Pediatric Surgery International
https://www.readbyqxmd.com/read/27651373/decreased-desmin-expression-in-the-developing-diaphragm-of-the-nitrofen-induced-congenital-diaphragmatic-hernia-rat-model
#19
Toshiaki Takahashi, Florian Friedmacher, Julia Zimmer, Prem Puri
PURPOSE: Congenital diaphragmatic hernia (CDH) is presumed to originate from defects in the primordial diaphragmatic mesenchyme, mainly comprising of muscle connective tissue (MCT). Thus, normal diaphragmatic morphogenesis depends on the structural integrity of the underlying MCT. Developmental mutations that inhibit normal formation of diaphragmatic MCT have been shown to result in CDH. Desmin (DES) is a major filament protein in the MCT, which is essential for the tensile strength of the developing diaphragm muscle...
December 2016: Pediatric Surgery International
https://www.readbyqxmd.com/read/27592368/lipocalin-2-as-a-new-biomarker-for-fetal-lung-hypoplasia-in-congenital-diaphragmatic-hernia
#20
Hiroyuki Tsuda, Tomomi Kotani, Tomoko Nakano, Kenji Imai, Shima Hirako, Hua Li, Fumitaka Kikkawa
BACKGROUND: Congenital diaphragmatic hernia (CDH) causes pulmonary hypoplasia, which are often fatal. We established a new biomarker for fetal lung hypoplasia in CDH. METHODS: We collected newborn lung tissue specimens at E21 from normal and nitrofen-induced CDH rats (administered 100mg orally at E9) and performed a microarray analysis and real-time PCR (RT-PCR). Sixty-three human amniotic fluid (AF) samples, including samples from isolated CDH cases (n=33) and Cesarean section (CS) cases without fetal complications (controls) (n=30), were obtained...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
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