Preclinical neonatal rat studies of heparin-binding EGF-like growth factor in protection of the intestines from necrotizing enterocolitis.

Abstract:

:We have previously demonstrated that enterally administered heparin-binding EGF-like growth factor (HB-EGF) produced in Escherichia coli decreases the incidence and severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis (NEC). In preparation for upcoming human clinical trials, large-scale production of HB-EGF according to Good Manufacturing Practice (GMP) has been successfully accomplished using a Pichia pastoris yeast system. The current studies used a neonatal rat model of NEC to elucidate several important preclinical characteristics of HB-EGF therapy. We found that enteral administration of HB-EGF (800 microg/kg/dose) four times a day effectively reduced the incidence and severity of NEC, that Pichia-derived HB-EGF was not significantly different from E. coli-derived HB-EGF in preventing NEC, that EGF was not superior to HB-EGF in preventing NEC, and that prophylactic administration of HB-EGF added to formula starting with the first feed or 12 h later significantly reduced the incidence of NEC, with no change in the incidence of NEC noted if HB-EGF was added to the formula starting 24, 48, or 72 h after birth. Thus, large-scale production of GMP-grade HB-EGF in Pichia pastoris yeast produces a biologically active molecule suitable for human clinical trials.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Radulescu A,Zorko NA,Yu X,Besner GE

doi

10.1203/PDR.0b013e3181994fa0

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

437-42

issue

4

eissn

0031-3998

issn

1530-0447

journal_volume

65

pub_type

杂志文章
  • Endodermal and mesenchymal cross talk: a crossroad for the maturation of foregut organs.

    abstract::The developmental stages of each foregut organ are intimately linked to the development of the other foregut organs such that the ultimate function of any one foregut organ, such as the metabolic function of the liver, depends on organizational changes associated with the maturation of multiple foregut organs. These c...

    journal_title:Pediatric research

    pub_type: 杂志文章,评审

    doi:10.1038/pr.2013.201

    authors: Arterbery AS,Bogue CW

    更新日期:2014-01-01 00:00:00

  • Comparative hemodynamic effects of isoproterenol, dopamine, and dobutamine in the newborn dog.

    abstract::To compare the hemodynamic effects of isoproterenol, dopamine, and dobutamine in the immature animal, each drug was infused into anesthetized open chest puppies and cardiac output was measured, as were systemic arterial blood pressure, heart rate, and renal artery blood flow. Cardiac output was increased by dopamine a...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-197909000-00011

    authors: Driscoll DJ,Gillette PC,Lewis RM,Hartley CJ,Schwartz A

    更新日期:1979-09-01 00:00:00

  • Hypoxia-induced post-translational changes in red blood cell protein map of newborns.

    abstract::Tyrosine (Tyr) phosphorylation is implicated in the modification of several erythrocyte functions, such as metabolic pathways and membrane transport, as well as in signal transduction systems. Here we describe the map of Tyr-phosphorylated soluble proteins of newborn red blood cells (RBC) using an in vitro model simul...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.PDR.0000180545.24457.AC

    authors: Marzocchi B,Ciccoli L,Tani C,Leoncini S,Rossi V,Bini L,Perrone S,Buonocore G

    更新日期:2005-10-01 00:00:00

  • Inotropic effect of increasing concentration of Ca2+ in the fetal rat heart with retinoic acid-induced malformations.

    abstract::Cardiac malformations (pulmonary trunk stenosis, ventricular septal defect, and double outlet right ventricle) were induced by the administration of two doses of retinoic acid (RA) to Wistar rats on d 13 of pregnancy. Contractile performance of the isolated perfused rat heart and its inotropic response to Ca2+ (0.6-10...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199512000-00011

    authors: Ostádalová I,Pexieder T,Ostádal B,Kolár F

    更新日期:1995-12-01 00:00:00

  • Ontogeny of hepatic type I insulin-like growth factor receptors in the rat.

    abstract::We studied the pre- and postnatal developmental regulation of the hepatic type I IGF receptor in the rat. Fetal rat liver membranes bound IGF-I throughout the latter part of gestation (d 17 to 21). After birth, binding diminished rapidly, reaching barely detectable levels by the 13th postnatal d. However, the presence...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199103000-00002

    authors: Gruppuso PA,Walker TD,Carter PA

    更新日期:1991-03-01 00:00:00

  • Beta-glucuronidase deficiency in a dog: a model of human mucopolysaccharidosis VII.

    abstract::This report describes a third mucopolysaccharidosis in animals: canine mucopolysaccharidosis VII. The affected dog was the offspring of a father-daughter mating. Weakness in the rear legs was evident at 8 weeks of age and became progressively worse. He had a large head, a shortened maxilla, and corneal granularities. ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198410000-00014

    authors: Haskins ME,Desnick RJ,DiFerrante N,Jezyk PF,Patterson DF

    更新日期:1984-10-01 00:00:00

  • Mutations of genes involved in the innate immune system as predictors of sepsis in very low birth weight infants.

    abstract::Mutations of genes involved in the innate immune system have been reported to be associated with an increased sepsis rate in adults. We determined the -159T mutation of the CD14 gene, the 896G mutation of the toll-like receptor 4 gene, the 3020insC mutation of the NOD2 gene (NOD2-3020insC), the IL-6 174G/C promoter po...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.PDR.0000112100.61253.85

    authors: Ahrens P,Kattner E,Köhler B,Härtel C,Seidenberg J,Segerer H,Möller J,Göpel W,Genetic Factors in Neonatology Study Group.

    更新日期:2004-04-01 00:00:00

  • Circulating interferon-gamma and white matter brain damage in preterm infants.

    abstract::The fetal inflammatory response has been suggested as causal in neonatal morbidity. Serial levels of circulating cytokines were evaluated in 74 infants with a mean gestational age (GA) of 27.1 wk. Pro-inflammatory [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1 beta, IL-2, IL-6, IL-8, IL-1...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.PDR.0000182592.76702.E8

    authors: Hansen-Pupp I,Harling S,Berg AC,Cilio C,Hellström-Westas L,Ley D

    更新日期:2005-11-01 00:00:00

  • Maturation of jejunal phosphate transport by rat brush border membrane vesicles.

    abstract::The transport of phosphate into jejunal brush border membrane vesicles isolated from 14- to 42-day-old rats was investigated using a rapid filtration technique. The presence of a sodium gradient enhanced phosphate uptake at all ages. Both sodium-dependent phosphate uptake and passive phosphate uptake declined with inc...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198512000-00021

    authors: Borowitz SM,Ghishan FK

    更新日期:1985-12-01 00:00:00

  • Patterns of mucosal inflammation in pediatric inflammatory bowel disease: striking overexpression of IL-17A in children with ulcerative colitis.

    abstract:BACKGROUND:Aberrant immune responses play a key role in the pathogenesis of inflammatory bowel disease (IBD). Most studies conducted to delineate the underlying molecular mechanisms focus on adults; an understanding of these mechanisms in children remains to be determined. Here, cytokines and transcription factors prod...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-019-0486-5

    authors: Busch MA,Gröndahl B,Knoll RL,Pretsch L,Doganci A,Hoffmann I,Kullmer U,Bähner V,Zepp F,Meyer CU,Gehring S

    更新日期:2020-04-01 00:00:00

  • Perspectives from the Society for Pediatric Research: Decreased Effectiveness of the Live Attenuated Influenza Vaccine.

    abstract::The intranasal live attenuated influenza vaccine (LAIV), FluMist, has been widely appreciated by pediatricians, parents, and children alike for its ease of administration. However, concerns regarding lack of effectiveness in recent influenza seasons led to the CDC Advisory Committee on Immunization Practices (ACIP) re...

    journal_title:Pediatric research

    pub_type: 杂志文章,评审

    doi:10.1038/pr.2017.239

    authors: Gill MA,Schlaudecker EP

    更新日期:2018-01-01 00:00:00

  • Pulmonary toxicity of monocrotaline differs at critical periods of lung development.

    abstract::We injected 3-day-old (neonatal), 8-day-old (infant), and 8-wk-old (adult) Sprague-Dawley rats with monocrotaline to examine the effect of a toxic agent at various stages of lung development. Two and four weeks after injection the rats were killed and the heart and lungs removed: the right and left ventricles were sep...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198507000-00019

    authors: Todd L,Mullen M,Olley PM,Rabinovitch M

    更新日期:1985-07-01 00:00:00

  • Apoptosis inhibitor of macrophage as a biomarker for disease activity in Japanese children with IgA nephropathy and Henoch-Schönlein purpura nephritis.

    abstract:BACKGROUND:To evaluate the apoptosis inhibitor of macrophage (AIM) deposition patterns on the kidneys of children with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) and to investigate the clinical usefulness of serum and/or urinary AIM levels as biomarkers for the disease activity. METHODS:Immun...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-020-0951-1

    authors: Irabu H,Shimizu M,Kaneko S,Inoue N,Mizuta M,Tasaki Y,Ohta K,Yachie A,Wada T

    更新日期:2020-05-14 00:00:00

  • Effect of low dose dopamine on hemodynamic and renal function in children.

    abstract::The purpose of the study was to investigate the effect of low doses of dopamine in children. Fourteen cases were studied after open heart surgery. Cardiac output and renal parameters were determined under baseline conditions and under continuous infusion of dopamine 2.5 and 5 micrograms/kg/min. During the control peri...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198909000-00009

    authors: Girardin E,Berner M,Rouge JC,Rivest RW,Friedli B,Paunier L

    更新日期:1989-09-01 00:00:00

  • Interleukin (IL)-1 beta in tracheal aspirates from premature infants induces airway epithelial cell IL-8 expression via an NF-kappa B dependent pathway.

    abstract::Tracheal aspirate IL-8 concentration and airway epithelial cell IL-8 expression are each increased in premature infants undergoing mechanical ventilation. We sought to determine the cytokines responsible for IL-8 expression in this context. Tracheal aspirates were collected from 18 mechanically ventilated premature in...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.PDR.0000145274.47221.10

    authors: Shimotake TK,Izhar FM,Rumilla K,Li J,Tan A,Page K,Brasier AR,Schreiber MD,Hershenson MB

    更新日期:2004-12-01 00:00:00

  • Endotoxin-induced hypoxic-ischemic tolerance is mediated by up-regulation of corticosterone in neonatal rat.

    abstract::Previous studies suggest that the endotoxin lipopolysaccharide (LPS) may have dual effects on brain damage induced by hypoxia-ischemia (HI) in 7-d-old rats, depending on the exposure paradigm. Although a 4-h interval between LPS administration and HI results in sensitization to HI brain injury, tolerance is observed w...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.pdr.0000191140.87314.ce

    authors: Ikeda T,Yang L,Ikenoue T,Mallard C,Hagberg H

    更新日期:2006-01-01 00:00:00

  • Autism spectrum disorders in extremely preterm infants and placental pathology findings: a matched case-control study.

    abstract:BACKGROUND:The prevalence of autism spectrum disorders (ASD) is 5-fold higher in preterm (PT) infants born ≤28 weeks gestational age (GA) as compared to the general population. The relationship between placental pathologic lesions and ASD in PT infants has not been studied. OBJECTIVES:The objective of this study was t...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-020-01160-4

    authors: Mir IN,White SP,Steven Brown L,Heyne R,Rosenfeld CR,Chalak LF

    更新日期:2020-09-19 00:00:00

  • Effect of sodium restriction and angiotensin II infusion in Bartter's syndrome.

    abstract::Five patients with Bartter's syndrome were investigated. Sodium restriction (less than 10 mEq/day for at least 5 days) showed a renal sodium wastage in only two patients (I and II) in spite of increased aldosterone secretion rate (from 151-427 to 680-842 mug/day). The effect of angiotensin II (A II) 80ng/kg/min for 30...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-197612000-00005

    authors: Sann L,David M,Richard P,Floret D,Sassard J,Bizollon CA,Francois R

    更新日期:1976-12-01 00:00:00

  • Glucose kinetics in glucose-infused small for gestational age infants.

    abstract::To evaluate the maturation of glucose homeostasis in the small for gestational age (SGA) neonate, glucose kinetics were measured with 78% enriched D-[U-13C]glucose by the prime plus constant infusion technique in nine SGA infants and compared with the rate obtained in seven term appropriate for gestational age infants...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:

    authors: Cowett RM,Susa JB,Oh W,Schwartz R

    更新日期:1984-01-01 00:00:00

  • Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts.

    abstract:BACKGROUND:Angiotensin (ANG) II is involved in experimental hyperoxia-induced lung fibrosis. Angiotensin-converting enzyme-2 (ACE-2) degrades ANG II and is thus protective, but is downregulated in adult human and experimental lung fibrosis. Hyperoxia is a known cause of chronic fibrotic lung disease in neonates, but th...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2015.27

    authors: Oarhe CI,Dang V,Dang M,Nguyen H,Gopallawa I,Gewolb IH,Uhal BD

    更新日期:2015-05-01 00:00:00

  • Selective impairment of taurine transport by cyclosporin A in a human placental cell line.

    abstract::We investigated, using a human placental choriocarcinoma cell line as a model, the effects of the immunosuppressive drug cyclosporin A on several placental transport systems mediating the transfer of glucose and amino acids from mother to fetus. The results of the investigation show that the transport system responsib...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199207000-00024

    authors: Ramamoorthy S,Leibach FH,Mahesh VB,Ganapathy V

    更新日期:1992-07-01 00:00:00

  • Tracheal banding in weanling rats diminishes lung growth and alters lung architecture.

    abstract::We banded the trachea of 4-wk-old male rats and studied lung growth, lung morphometry, and static pulmonary mechanics 4 wk later. We compared the experimental animals to sham-operated male littermates of the same age, 8-wk-old normal male littermates, and weight-matched rats of a younger age. Tracheal banded animals w...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198103000-00014

    authors: Kida K,Thurlbeck WM

    更新日期:1981-03-01 00:00:00

  • Prevalence of GB virus C/hepatitis G virus ribonucleic acid and anti-hepatitis G virus-E2 antibodies among Japanese children with histories of transfusions or with liver diseases.

    abstract::To clarify the prevalence of Japanese children thought to be at a risk for infection with GB virus-C (GBV-C)/hepatitis G virus (HGV), we investigated the detection rates of serum GBV-C/ HGV ribonucleic acid (RNA) by reverse transcription-seminested PCR and serum anti-HGV-E2 antibody by ELISA in 162 children with histo...

    journal_title:Pediatric research

    pub_type: 临床试验,杂志文章

    doi:10.1203/00006450-199901000-00021

    authors: Goto K,Sugiyama K,Li R,Miyake Y,Ando T,Mizutani F,Terabe K,Mizuno K,Wada Y

    更新日期:1999-01-01 00:00:00

  • A micromethod for the analysis of cryoglobulins via laser nephelometry: evaluation and comparison to C1q binding activity in autoimmune diseases in pediatrics.

    abstract::Quantitative determinations of cryoglobulins (IgG, IgA, IgM, and C3) were performed by a laser nephelometry microtechnique on 250 serum samples from a group of pediatric patients suspected of having immune complex-mediated disorders. Approximately 50% of these samples were cryoglobulin positive. Patients with cryoglob...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198007000-00003

    authors: Yang LC,Norman ME,Doughty RA

    更新日期:1980-07-01 00:00:00

  • Functional development of fat absorption in term and preterm neonates strongly correlates with ability to absorb long-chain Fatty acids from intestinal lumen.

    abstract::Our goal for this study was to determine whether the maturation of fat absorption in neonatal life is functionally related to an increased ability to hydrolyze dietary fat, to absorb long-chain fatty acids, or to do both. In 16 preterm and in eight term neonates, the intestinal ability to hydrolyze triacylglycerols an...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-200201000-00011

    authors: Rings EH,Minich DM,Vonk RJ,Stellaard F,Fetter WP,Verkade HJ

    更新日期:2002-01-01 00:00:00

  • Increased beta-lactoglobulin absorption during rotavirus enteritis in infants: relationship to sugar permeability.

    abstract::We studied absorption of the potentially allergenic protein beta-lactoglobulin during acute rotavirus diarrhea in infants and assessed the relationship of this macromolecular absorption with intestinal sugar permeability. After oral rehydration, 38 patients with acute gastroenteritis were given orally a 100-ml solutio...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199109000-00019

    authors: Jalonen T,Isolauri E,Heyman M,Crain-Denoyelle AM,Sillanaukee P,Koivula T

    更新日期:1991-09-01 00:00:00

  • NeoDoppler: New ultrasound technology for continous cerebral circulation monitoring in neonates.

    abstract:BACKGROUND:There is a strong need for continuous cerebral circulation monitoring in neonatal care, since suboptimal cerebral blood flow may lead to brain injuries in preterm infants and other critically ill neonates. NeoDoppler is a novel ultrasound system, which can be gently fixed to the anterior fontanel and measure...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-019-0535-0

    authors: Vik SD,Torp H,Follestad T,Støen R,Nyrnes SA

    更新日期:2020-01-01 00:00:00

  • Hemodynamic homeostasis during acute hypoxia in septic and nonseptic piglets: differential role of prostaglandins and nitric oxide.

    abstract::We studied the hemodynamic responses of 29 anesthetized and mechanically ventilated piglets to acute hypoxia [reduction of Pao2 from 130 to 38 mm Hg induced by inhalation of 7% fraction of inspired oxygen (Fio2) for 7.5 min] before and during group B beta-hemolytic streptococci (GBS) sepsis. During hypoxia, nonseptic ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-200004000-00017

    authors: Rudinsky B,Hipps R,Bell A,Lozon M,Meadow W

    更新日期:2000-04-01 00:00:00

  • Impairment of rat postnatal lung alveolar development by glucocorticoids: involvement of the p21CIP1 and p27KIP1 cyclin-dependent kinase inhibitors.

    abstract::It has been shown that glucocorticoids accelerate lung development by limiting alveolar formation resulting from a premature maturation of the alveolar septa. Based on these data, the aim of the present work was to analyze the influence of dexamethasone on cell cycle control mechanisms during postnatal lung developmen...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-200202000-00008

    authors: Corroyer S,Schittny JC,Djonov V,Burri PH,Clement A

    更新日期:2002-02-01 00:00:00

  • Multiple mechanisms of lung surfactant inhibition.

    abstract::We studied the mechanisms by which C16:0 lysophosphatidylcholine (LPC) and albumin inhibit the surface activity of calf lung surfactant extract (CLSE) by using a pulsating bubble apparatus with a specialized hypophase exchange system, plus adsorption and Wilhelmy balance measurements. In the absence of inhibitors, CLS...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199907000-00015

    authors: Holm BA,Wang Z,Notter RH

    更新日期:1999-07-01 00:00:00