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Dmitry Morozov, Olga Morozova, Dmitri Pervouchine, Lubov Severgina, Alexei Tsyplakov, Natalya Zakharova, Nikita Sushentsev, Larisa Maltseva, Ivan Budnik
BackgroundSurgical treatment for gastroschisis and congenital diaphragmatic hernia (CDH) commonly leads to abdominal compartment syndrome (ACS) associated with hypoxic renal injury. We hypothesized that measurement of urinary and serum concentrations of vascular endothelial growth factor (VEGF), π-glutathione S-transferase (π-GST), and monocyte chemoattractant protein-1 (MCP-1) may serve for noninvasive detection of hypoxic renal injury in such patients.MethodsIntra-abdominal pressure (IAP), renal excretory function, and the biomarker levels were analyzed before, 4, and 10 days after surgery...
November 15, 2017: Pediatric Research
Thomas Schaible, Janine Reineke, Ludwig Gortner, Dominik Monz, Regine Schaffelder, Erol Tutdibi
Background This study investigates plasma cytokine levels in neonates with the more common left-sided congenital diaphragmatic hernia (CDH) and correlates them with severity of disease indicated by position of the liver. An intrathoracic part of liver is associated with higher need for extracorporeal membrane oxygenation (ECMO) and higher risk for chronic lung disease (CLD). Methods A total of 28 newborns with CDH were subdivided by their liver position in partially intrathoracic (n = 16) and only abdominal (n = 12) position...
June 2017: American Journal of Perinatology
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
Augusto Frederico Schmidt, Frances Lilian Lanhellas Gonçalves, Rebeca Lopes Figueira, Federico Scorletti, Jose Luis Peiró, Lourenço Sbragia
AIM: To investigate the effect of combined prenatal treatment with retinoic acid (RA) and tracheal occlusion (TO) on the pulmonary vascular morphology and expression of vascular endothelial growth factors (VEGF) and its receptors in a rat model of congenital diaphragmatic hernia (CDH). MATERIAL AND METHODS: Rats were given nitrofen at 9 days of gestation followed by no treatment (CDH), RA (CDH + RA), TO (CDH + TO), or both (CDH + RA + TO) (n = 16). We measured the median wall thickness of the pulmonary arterioles (MWT) and analyzed the expression of VEGF and its receptors (VEGFR1 and VEGFR2)...
June 2016: Pediatric Surgery International
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
Coralie L Guerin, Xavier Loyer, José Vilar, Audrey Cras, Tristan Mirault, Pascale Gaussem, Jean-Sébastien Silvestre, David M Smadja
Very small embryonic-like stem cells (VSELs) are multipotent stem cells localised in adult bone marrow (BM) that may be mobilised into peripheral blood (PB) in response to tissue injury. We aimed to quantify VSELs in BM and PB of patients with critical limb ischaemia (CLI) and to test their angiogenic potential in vitro as well as their therapeutic capacity in mouse model of CLI. We isolated BM VSELs from patients with CLI and studied their potential to differentiate into vascular lineages. Flow and imaging cytometry showed that VSEL counts were lower in BM (p< 0...
May 2015: Thrombosis and Haemostasis
Frances Lilian Lanhellas Gonçalves, Rebeca Lopes Figueira, Ana Leda Bertoncini Simões, Rodrigo Melo Gallindo, Allan Coleman, José Luis Peiró, Lourenço Sbragia
PURPOSE: The use of dexamethasone (Dx) stimulates growth, fetal lung maturation and can improve pulmonary hypertension in congenital diaphragmatic hernia (CDH). Our aim was to evaluate the effect of Dx on the lung after fetal pulmonary ventilation in the CDH rat model. METHODS: Some groups underwent prenatal treatment with dexamethasone (0.4 mg/kg) that was given at 18.5 gestational day (GD). Sprague-Dawley rat fetuses were divided into groups: control (C); ventilated control (CV); control exposed to dexamethasone (CDx); ventilated control exposed to dexamethasone (CVDx); congenital diaphragmatic hernia (CDH), ventilated CDH (CDHV), CDH exposed to dexamethasone (CDHDx) and ventilated CDH exposed to dexamethasone (CDHVDx)...
December 2014: Pediatric Surgery International
L Sbragia, A C C Nassr, F L L Gonçalves, A F Schmidt, C C Zuliani, P V Garcia, R M Gallindo, L A V Pereira
Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH...
February 2014: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Shannon N Acker, Gregory J Seedorf, Steven H Abman, Eva Nozik-Grayck, David A Partrick, Jason Gien
Decreased lung vascular growth and pulmonary hypertension contribute to poor outcomes in congenital diaphragmatic hernia (CDH). Mechanisms that impair angiogenesis in CDH are poorly understood. We hypothesize that decreased vessel growth in CDH is caused by pulmonary artery endothelial cell (PAEC) dysfunction with loss of a highly proliferative population of PAECs (HP-PAEC). PAECs were harvested from near-term fetal sheep that underwent surgical disruption of the diaphragm at 60-70 days gestational age. Highly proliferative potential was measured via single cell assay...
December 2013: American Journal of Physiology. Lung Cellular and Molecular Physiology
Eveline Shue, Jianfeng Wu, Samuel Schecter, Doug Miniati
PURPOSE: Many infants develop a postsurgical chylothorax after diaphragmatic hernia repair. The pathogenesis remains elusive but may be owing to dysfunctional lymphatic development. This study characterizes pulmonary lymphatic development in the nitrofen mouse model of CDH. METHODS: CD1 pregnant mice were fed nitrofen/bisdiamine (N/B) or olive oil at E8.5. At E14.5 and E15.5, lung buds were categorized by phenotype: normal, N/B without CDH (N/B - CDH), or N/B with CDH (N/B+CDH)...
June 2013: Journal of Pediatric Surgery
E Sanz-López, E Maderuelo, D Peláez, P Chimenti, R Lorente, M A Muñoz, M Sánchez-Luna
Introduction. Vascular endothelial growth factor (VEGF), an angiogenic factor secreted by type II pneumocytes, could play a role in congenital diaphragmatic hernia (CDH) pathogenesis. Animal studies suggest that VEGF accelerates lung growth. Aim. To quantify VEGF on fetal lungs in a nitrofen rat model for CDH and to analyze the effect of tracheal occlusion (TO) in VEGF in fetal lung rats after nitrofen and in control rats not exposed to nitrofen. Methods. Pregnant rats received nitrofen on day 9.5 of gestation...
2013: Critical Care Research and Practice
Augusto F Schmidt, Frances L L Gonçalves, Aline C Regis, Rodrigo M Gallindo, Lourenço Sbragia
OBJECTIVE: We sought to investigate the effects of antenatal retinoic acid on the pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model. STUDY DESIGN: Rat fetuses were exposed to nitrofen at gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days 18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF, VEGFR1, and VEGFR2 expression was analyzed by Western blotting and immunohistochemistry...
July 2012: American Journal of Obstetrics and Gynecology
Irene W J M van der Horst, Prapapan Rajatapiti, Paul van der Voorn, Francien H van Nederveen, Dick Tibboel, Robbert Rottier, Irwin Reiss, Ronald R de Krijger
Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension and has high morbidity and mortality rates. The cause and pathophysiology of CDH are not fully understood. However, impaired angiogenesis appears to play an important role in the pathophysiology of CDH. Therefore, we examined different components of an important pathway in angiogenesis: hypoxia-inducible factors (HIFs); HIF regulators von Hippel-Lindau (VHL) and prolyl 3-hydroxylase (PHD3); and HIF target genes vascular endothelial growth factor A ( VEGF-A ) and vascular endothelial growth factor receptor 2 ( VEGFR-2 )...
September 2011: Pediatric and Developmental Pathology
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
Katharina Meier, Claus-Michael Lehr, Nicole Daum
Pancreatic stem cells (PSC) have proved their high plasticity by differentiating into cell types of all three germ layers after the formation of organoid bodies. Motivated by this high differentiation potential this study focused on the immanent stem cell, endothelial and epithelial characteristics of PSC to elucidate whether PSC are a possible source for a stem cell-based in vitro model for screening of pharmaceutical substances. Furthermore, it was investigated whether marker expression was influenced by application of protocols for inducing endothelial or epithelial differentiation originating from research with mesenchymal stem cells or by cultivation on extracellular matrices (ECM)...
January 2009: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Jianli Niu, Asim Azfer, Olga Zhelyabovska, Sumbul Fatma, Pappachan E Kolattukudy
Monocyte chemotactic protein-1 (MCP-1) has been recognized as an angiogenic chemokine. The molecular mechanism of MCP-1-mediated angiogenesis remains unknown. We recently identified a novel transcription factor, designated MCP-1-induced protein (MCPIP), in human monocytes after treatment with MCP-1. We investigated whether MCP-1-induced angiogenesis is mediated via MCPIP. Treatment of human umbilical vein endothelial cells (HUVECs) with MCP-1 induced expression of MCPIP and capillary-like tube formation. Knockdown of MCPIP by small interfering RNA (siRNA) suppressed MCP-1-induced angiogenesis-related gene VEGF and HIF-1alpha expression as well as tube formation...
May 23, 2008: Journal of Biological Chemistry
Akihiko Hara, Cheryl J Chapin, Robert Ertsey, Joseph A Kitterman
Vascular endothelial growth factor A (VEGF-A) is essential for normal pulmonary vascular and parenchymal development. Changes in fetal lung distension profoundly affect lung growth and maturation, including vascular development. To define developmental lung expression of VEGF-A and its receptors and investigate effects of changes in fetal lung distension, we studied fetal rats at embryonic day (ED) 16, 19, and 22, postnatal rats at postnatal day (PD) 5, 10, and 21, and adult rats. We used reverse transcriptase PCR to measure mRNA expression for VEGF-A isoforms (VEGF-A(120), (-144), (-164), and (-188)) and VEGF-A receptors, Flt-1 and Flk-1...
July 2005: Pediatric Research
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
Robert Chang, Steven Andreoli, Yin-Shan Ng, Thanh Truong, Sandra R Smith, Jay Wilson, Patricia A D'Amore
BACKGROUND: Vascular endothelial growth factor (VEGF) is upregulated in pulmonary alveolarization. However, developmental expression of pulmonary VEGF and its possible role in the pathogenesis of CDH are not well described. METHODS: Timed-pregnant VEGF-LacZ mice, possessing a beta-galactosidase reporter introduced into the 3' region of the VEGF gene, were used to examine fetal lung gene expression in a model of nitrofen-induced CDH. RESULTS: VEGF gene expression increased from embryonic day 13 until its peak at embryonic day 16 and then decreased until term in all groups...
June 2004: Journal of Pediatric Surgery
T Oue, A Yoneda, H Shima, Y Taira, P Puri
Persistent pulmonary hypertension (PPH) in congenital diaphragmatic hernia (CDH) lung has been shown to be associated with structural changes in the pulmonary vasculature, including medial and adventitial thickening. Vascular endothelial growth factor (VEGF) is a potent mitogenic and permeability factor targeting predominantly endothelial cells. mRNA encoding VEGF is detected in all fetal tissues and is most abundant in fetal lung, kidney, and liver. Recently, antenatal dexamethasone (Dex) treatment has been shown to prevent pulmonary-artery structural changes in experimentally-produced CDH...
May 2002: Pediatric Surgery International
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