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Hideshi Fujinaga, Hiroko Fujinaga, Nobuyuki Watanabe, Tomoko Kato, Moe Tamano, Miho Terao, Shuji Takada, Yushi Ito, Akihiro Umezawa, Masahiko Kuroda
Vascular growth is necessary for normal lung development. Although endothelial progenitor cells (EPCs) play an important role in vascularization, little is known about EPC function in congenital diaphragmatic hernia (CDH), a severe neonatal condition that is associated with pulmonary hypoplasia. We hypothesized that the function of endothelial colony-forming cells (ECFCs), a type of EPC, is impaired in CDH. Cord blood (CB) was collected from full-term CDH patients and healthy controls. We assessed CB progenitor cell populations as well as plasma vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1α (SDF1α) levels...
June 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Rodrigo Melo Gallindo, Frances Lilian Lanhellas Gonçalves, Rebeca Lopes Figueira, Luís Antônio Violin Dias Pereira, Ana Leda Bertoncini Simões, Augusto Frederico Schmidt, Lourenço Sbragia
BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is a defect that presents high mortality because of pulmonary hypoplasia and hypertension. Mechanical ventilation changes signaling pathways, such as nitric oxide and VEGF in the pulmonary arterioles. We investigated the production of NOS2 and NOS3 and expression of VEGF and its receptors after ventilation in rat fetuses with CDH. METHODS: CDH was induced by Nitrofen. The fetuses were divided into 6 groups: 1) control (C); 2) control ventilated (CV); 3) exposed to nitrofen (N-); 4) exposed to nitrofen ventilated (N-V), 5) CDH and 6) CDH ventilated (CDHV)...
May 2015: Journal of Pediatric Surgery
Martine Makanga, Hidekazu Maruyama, Celine Dewachter, Agnès Mendes Da Costa, Emeline Hupkens, Geoffrey de Medina, Robert Naeije, Laurence Dewachter
Congenital diaphragmatic hernia (CDH) has a high mortality rate mainly due to lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). Simvastatin has been shown to prevent the development of pulmonary hypertension (PH) in experimental models of PH. We, therefore, hypothesized that antenatal simvastatin would attenuate PPHN in nitrofen-induced CDH in rats. The efficacy of antenatal simvastatin was compared with antenatal sildenafil, which has already been shown to improve pathological features of PPHN in nitrofen-induced CDH...
April 1, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Eveline H Shue, Samuel C Schecter, Wenhui Gong, Mozziyar Etemadi, Michael Johengen, Corey Iqbal, S Christopher Derderian, Peter Oishi, Jeffrey R Fineman, Doug Miniati
PURPOSE: Pulmonary hypertension (pHTN), a main determinant of survival in congenital diaphragmatic hernia (CDH), results from in utero vascular remodeling. Phosphodiesterase type 5 (PDE5) inhibitors have never been used antenatally to treat pHTN. The purpose of this study is to determine if antenatal PDE5 inhibitors can prevent pHTN in the fetal lamb model of CDH. METHODS: CDH was created in pregnant ewes. Postoperatively, pregnant ewes received oral placebo or tadalafil, a PDE5 inhibitor, until delivery...
January 2014: Journal of Pediatric Surgery
Hiroshi Denda, Shinji Kimura, Akiyoshi Yamazaki, Noboru Hosaka, Yuichi Takano, Kenji Imura, Yoichi Yajiri, Naoto Endo
In animal models of degenerative lumbar disease, inducible nitric oxide synthase (iNOS) is expressed in macrophages and Schwann cells following compression of the cauda equina. We previously reported that NO metabolites (nitrite plus nitrate: [NOx]) in the cerebrospinal fluid (CSF) correlate with postoperative pain relief in patients with degenerative lumbar disease and with neurologic recovery rate postoperatively or after conservative treatment in patients with spinal cord injury. The objective of the present study was to examine the relationship between [NOx] and neurologic severity, and recovery in degenerative cervical and lumbar diseases...
April 2011: European Spine Journal
Beena G Sood, Susan Wykes, Marina Landa, Lilia De Jesus, Raja Rabah
BACKGROUND: Neonatal hypoxemic respiratory failure (NHRF) is usually associated with reversible persistent pulmonary hypertension (PPHN). Congenital diaphragmatic hernia (CDH), a cause of refractory NHRF, is associated with irreversible pulmonary hypertension. Nitric oxide (NO) generated in the pulmonary vascular endothelium by endothelial nitric oxide synthase (eNOS) plays a pivotal role in perinatal circulatory adaptation. OBJECTIVE: To compare the expression of eNOS using IHC in postmortem lung tissue from newborns diagnosed clinically with PPHN and CDH...
February 2011: Experimental and Molecular Pathology
Kristin M Caspers, Cristiana Oltean, Paul A Romitti, Lixian Sun, Barbara R Pober, Sonja A Rasmussen, Wei Yang, Charlotte Druschel
BACKGROUND: Congenital diaphragmatic hernia (CDH) is a major birth defect that occurs when abdominal organs herniate through a diaphragmatic opening into the thoracic cavity and is associated with high mortality (>50%). The etiology of CDH is not well understood. METHODS: Using data from the National Birth Defects Prevention Study, we examined associations between CDH and maternal periconceptional exposure (1 month before through the third month of pregnancy) to cigarette smoking and alcohol...
December 2010: Birth Defects Research. Part A, Clinical and Molecular Teratology
Olivier Boucherat, Marie-Laure Franco-Montoya, Christophe Delacourt, Jelena Martinovic, Virginie Masse, Caroline Elie, Bernard Thébaud, Alexandra Benachi, Jacques R Bourbon
Lung hypoplasia (LH) is a life-threatening congenital abnormality with various causes. It involves vascular bed underdevelopment with abnormal arterial muscularization leading to pulmonary hypertension. Because underlying molecular changes are imperfectly known and sometimes controversial, we determined key factors of angiogenesis along intrauterine development, focusing at the angiopoietin (ANG)/Tie-2 system. Lung specimens from medical terminations of pregnancy (9-37 wk) were used, including LH due to congenital diaphragmatic hernia (CDH) or other causes, and nonpulmonary disease samples were used as controls...
June 2010: American Journal of Physiology. Lung Cellular and Molecular Physiology
A S de Buys Roessingh, P de Lagausie, J C Mercier, Y Aigrain, A T Dinh-Xuan
Endogenous nitric oxide (NO) mediates pulmonary vasodilatation at birth, but inhaled NO fails to reduce pulmonary vascular resistance (PVR) in newborns with congenital diaphragmatic hernia (CDH). This study was designed to investigate the effects of ventilation, and the nature of its endogenous mediator, in fetal lambs with experimental CDH. Investigations at 138 days of gestation showed that ventilation markedly decreased PVR. Inhibition of NO synthesis reduced ventilation-induced pulmonary vasodilatation in vivo and increased in vitro isometric tension of vascular rings...
September 2008: Experimental Lung Research
Anthony S de Buys Roessingh, Pascal de Lagausie, Taline Ebrahimian, Taline Ibrahima, Sy Duong-Quy, Jean-Christophe Schneider, Xiao-Lin Huang, Jean-Christophe Mercier, Yves Aigrain, Chantal Boulanger, Anh Tuan Dinh-Xuan
AIM: The aim of this study was to determine the presence of the neuronal nitric oxide synthase (nNOS) in near full-term lambs with congenital diaphragmatic hernia (CDH) and its role in the modulation of pulmonary vascular basal tone. METHODS: We surgically created diaphragmatic hernia on the 85th day of gestation. On the 135th, catheters were used to measure pulmonary pressure and blood flow. We tested the effects of 7-nitroindazole (7-NINA), a specific nNOS antagonist and of N-nitro-L-arginine (L-NNA), a nonspecific nitric oxide synthase antagonist...
April 2008: Pediatric Pulmonology
Sherif M K Shehata, Hari S Sharma, Wolter J Mooi, Dick Tibboel
The molecular basis of the pathogenesis of pulmonary hypertension (PH) associated with congenital diaphragmatic hernia (CDH) is poorly understood. Variation in responses to therapeutic strategies such as nitric oxide (NO) inhalation and extracorporeal membrane oxygenation (ECMO) in patients with CDH remains a major problem in pediatric critical care. We investigated the expression pattern of NO-generating enzyme nitric-oxide synthase (NOS) (both endothelial [eNOS] and inducible [iNOS] isoforms) in the lungs of CDH patients with PH and evaluated the influence of ECMO on the expression levels of these genes in an attempt to understand the underlying molecular mechanisms...
2006: Cell Biochemistry and Biophysics
Toko Shinkai, Hideki Shima, Valeria Solari, Prem Puri
The high mortality in patients with congenital diaphragmatic hernia (CDH) has been attributed to pulmonary hypoplasia and persistent pulmonary hypertension (PPH). Endothelin-1 (ET-1), nitric oxide (NO), and calcitonin gene-related peptide (CGRP) have been reported to be important vasoactive mediators in the perinatal pulmonary circulation. The exact mechanism by which these vasoactive mediators interact to regulate the perinatal pulmonary vascular tone in CDH with PPH is not fully understood. We hypothesized that the altered pulmonary vascular reactivity in CDH is due to imbalance in vasoactive mediators...
March 2005: Pediatric Surgery International
Jessica D de Rooij, Münnever Hösgör, Ynske Ijzendoorn, Robbert Rottier, Frederick A Groenman, Dick Tibboel, Ronald R de Krijger
Congenital diaphragmatic hernia (CDH) is a congenital disorder, complicated by pulmonary hypoplasia (PH) and pulmonary hypertension. Hypoplastic lungs have fewer and smaller airspaces than normal, with thicker interalveolar septa; the adventitia and media of pulmonary arteries are thickened, and the total size of the pulmonary vascular bed is decreased compared to normal. Although histological abnormalities in PH have been described, less is known about the underlying molecular mechanisms. Therefore, we have investigated a series of proteins, known to be involved in angiogenesis, including von Hippel-Lindau protein (pVHL), hypoxia-inducible factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk-1), and endothelial and inducible nitric oxide synthase (eNOS, iNOS) by immunohistochemistry on paraffin-embedded lung tissue of CDH patients ( n = 13), patients with lung hypoplasia due to other causes ( n = 20), and normal controls ( n = 33)...
September 2004: Pediatric and Developmental Pathology
Valeria Solari, Anna Piaseczna Piotrowska, Prem Puri
BACKGROUND/PURPOSE: Heme oxygenase (HO-1), an inducible isoform of HO is a regulator of vascular tone and cell proliferation through the production of endogenous carbon monoxide (CO). Endothelium-derived nitric oxide (NO) occurs in the endothelial layers of blood vessels and mediates vasorelaxation. Both CO and NO have similar properties and are potent vasodilators. The aim of this study was to examine the expression of HO-1 and endothelial nitric oxide synthase (eNOS) in the Congenital diaphragmatic hernia (CDI) lung...
May 2003: Journal of Pediatric Surgery
Bernard Thébaud, Thierry Petit, Pascal De Lagausie, Josette Dall'Ava-Santucci, Jean-Christophe Mercier, A Tuan Dinh-Xuan
Nitric oxide (NO) plays a major role in the modulation of perinatal pulmonary vascular tone. Congenital diaphragmatic hernia (CDH), a major cause of severe persistent pulmonary hypertension of the newborn (PPHN), is often refractory to inhaled NO. Alterations in NO/cyclic guanosine 3',5' monophosphate (cGMP)-mediated pulmonary vasodilatation may contribute to PPHN in CDH. We assessed NO/cGMP-mediated pulmonary vasorelaxation in vitro in 140-d gestational lamb fetuses with surgically created left CDH (term = 147 d) to age-matched controls...
July 2002: American Journal of Respiratory Cell and Molecular Biology
Paola Sarchielli, Andrea Alberti, Ardesio Floridi, Virgilio Gallai
Previous research of our group demonstrated an increase in L-arginine/nitric oxide (NO) pathway activity in patients with chronic daily headache (CDH) with a previous history of migraine, which was associated with a reduced platelet serotonin content and increased Ca(2+) levels. In the present work, we assessed the variations in L-arginine/NO pathway activity and platelet cyclic guanosine 3',5'-monophosphate (cGMP) levels in 25 patients affected by chronic tension-type headache (CTTH) (8 M, 17 F; age range: 34-54 years)...
June 15, 2002: Journal of the Neurological Sciences
M J Láinez, M J Monzón
Chronic daily headache (CDH) is a heterogeneous group of headaches that includes primary and secondary varieties. Primary CDH is a frequent entity that probably affects 4% to 5% of the population. It can be subdivided into headaches of short duration (less than 4 hours per attack), like chronic cluster headache, and disorders of long duration (greater than 4 hours per attack). Primary CDH of long duration includes transformed migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua...
March 2001: Current Neurology and Neuroscience Reports
B O Okoye, P D Losty, M J Fisher, I Wilmott, D A Lloyd
AIMS: To study the effect of prenatal glucocorticoid treatment on endothelial nitric oxide synthase (eNOS) expression in rats with congenital diaphragmatic hernia (CDH). METHODS: CDH was induced in fetal rats by the maternal administration of nitrofen on day 9.5 of gestation. Dexamethasone was administered on days 18.5 and 19.5 before delivery of the fetuses on days 20.5 and 21.5. Pulmonary eNOS protein expression was studied by western immunoblotting and immunohistochemistry...
May 1998: Archives of Disease in Childhood. Fetal and Neonatal Edition
M S Irish, P L Glick, J Russell, P Kapur, D A Bambini, B A Holm, R H Steinhorn
BACKGROUND/PURPOSE: Pulmonary hypertension plays a significant role in the pathophysiology of congenital diaphragmatic hernia (CDH). Although there has been an intensive research effort directed at mediators that may cause pulmonary vasoconstriction, no single agent has been identified. The authors hypothesize that there may be an alteration in the cGMP-nitric oxide (NO) pathway of vasodilatation contributing to the pulmonary hypertension observed in CDH. The purpose of these studies is to begin to elucidate vasoactive properties of pulmonary vessels with particular attention to the cGMP-NO pathway of vasodilatation in fetal lambs with CDH...
June 1998: Journal of Pediatric Surgery
T Okazaki, H S Sharma, S K McCune, D Tibboel
BACKGROUND: Pulmonary hypoplasia and persistent pulmonary hypertension (PPH) are the principal causes of the ongoing mortality in congenital diaphragmatic hernia (CDH) presenting with respiratory insufficiency within 6 hours after birth. Endothelin-1 (ET-1) is an endothelial-derived vasoconstrictor, which could play an important role in modulating pulmonary vascular tone in PPH. ET-1 exerts its role in controlling vascular tone through two different subtype receptors, endothelin-A receptor (ETA) which is responsible for vasoconstriction and endothelin-B receptor (ETB) which is responsible for vasodilatation by induction of nitric oxide synthase...
January 1998: Journal of Pediatric Surgery
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