Pediatric Research (Pediatr Res )

Publisher: International Pediatric Research Foundation, Lippincott, Williams & Wilkins

Journal description

Pediatric Research publishes original papers on research into the diseases, disorders and development of children, extending from molecular biology to epidemiology. Use of theoretical models, animals, or in vitro techniques relevant to developmental biology or medicine are acceptable as are human studies.

Current impact factor: 2.84

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013/2014 Impact Factor 2.84
2012 Impact Factor 2.673
2011 Impact Factor 2.7
2010 Impact Factor 2.803
2009 Impact Factor 2.607
2008 Impact Factor 2.604
2007 Impact Factor 2.839
2006 Impact Factor 2.619
2005 Impact Factor 2.875
2004 Impact Factor 2.875
2003 Impact Factor 3.064
2002 Impact Factor 3.382
2001 Impact Factor 3.289
2000 Impact Factor 2.794
1999 Impact Factor 2.671
1998 Impact Factor 3.098
1997 Impact Factor 2.661

Impact factor over time

Impact factor
Year

Additional details

5-year impact 2.90
Cited half-life 9.00
Immediacy index 0.63
Eigenfactor 0.02
Article influence 0.95
Website Pediatric Research website
Other titles Pediatric research
ISSN 0031-3998
OCLC 1761994
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

Lippincott, Williams & Wilkins

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
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  • Restrictions
    • 12 months embargo
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    • Pre-print must be removed upon acceptance for publication
    • Post-print may be deposited in personal website or institutional repository
    • Publisher's version/PDF cannot be used
    • Must include statement that it is not the final published version
    • Published source must be acknowledged with full citation
    • Set statement to accompany deposit
    • Must link to publisher version
    • NIH authors will have their accepted manuscripts transmitted to PubMed Central on their behalf after a 12 months embargo (see policy for details)
    • Wellcome Trust and HHMI authors will have their accepted manuscripts transmitted to PubMed Central on their behalf after a 6 months embargo (see policy for details)
    • If the hybrid open access option is not available, RCUK authors articles will be released as Creative Commons Attirbution Non-Commercial No Derivatives after a 6 months
    • Publisher last reviewed on 10/04/2014
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Three risk factors are associated with hemorrhagic forms of encephalopathy of prematurity (EP): (i) prematurity, (ii) in utero ischemia (IUI) or perinatal ischemia, and (iii) mechanical ventilation. We hypothesized that IUI would induce an angiogenic response marked by activation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), the latter degrading vascular basement membrane and increasing vulnerability to raised intravenous pressure during positive pressure mechanical ventilation.Methods We studied a rat model of hemorrhagic-EP characterized by periventricular hemorrhages in which a 20-min episode of IUI is induced at E19, pups are born naturally at E21-22, and on P0, are subjected to a 20-min episode of positive pressure mechanical ventilation. Tissues were studied by H&E staining, immunolabeling, immunoblot and zymography.ResultsMechanical ventilation of rat pups 2-3 days after 20-min IUI caused widespread hemorrhages in periventricular tissues. IUI resulted in upregulation of VEGF and MMP-9. Zymography confirmed significantly elevated gelatinase activity. MMP-9 activation was accompanied by severe loss of MMP-9 substrates, collagen IV and laminin, in microvessels in periventricular areas.Conclusions Our findings are consistent with the hypothesis that positive pressure mechanical ventilation of the newborn in the context of recent prenatal ischemia/hypoxia can predispose to periventricular hemorrhages.Pediatric Research (2015); doi:10.1038/pr.2015.34.
    Pediatric Research 02/2015;
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    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 the role of ACE-2 in neonatal lung fibrosis is unknown. We hypothesized that ACE-2 in human fetal lung cells might be downregulated by hyperoxic gas.Methods Fetal human lung fibroblast IMR90 cells were exposed to hyperoxic (95% O2/5% CO2) or normoxic (21% O2/5% CO2) gas in vitro. Cells and culture media were recovered separately for assays of ACE-2 enzymatic activity, mRNA and immunoreactive protein.ResultsHyperoxia decreased ACE-2 immunoreactive protein and enzyme activity in IMR90 cells (both p<0.01), but did not change ACE-2 mRNA. ACE-2 protein was increased in the cell supernatant, suggesting protease-mediated ectodomain shedding. TAPI-2, an inhibitor of TNF-α Converting Enzyme (TACE/ADAM17), prevented both the decrease in cellular ACE-2 and the increase in soluble ACE-2 (both p<0.05).Conclusions These data show that ACE-2 is expressed in fetal human lung fibroblasts but is significantly decreased by hyperoxic gas. They also suggest that hyperoxia decreases ACE-2 through a shedding mechanism mediated by ADAM17/TACE.Pediatric Research (2015); doi:10.1038/pr.2015.27.
    Pediatric Research 02/2015;
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    ABSTRACT: BackgroundNEC, an intestinal inflammatory disease affecting premature infants, is associated with low regulatory T (Treg) to effector T (Teff) cell ratios. We recently demonstrated that heme oxygenase-1 (HO-1) deficiency leads to increased NEC development. Here, we investigated the effects of HO-1 on T cell proportions in a murine NEC-like injury model.Methods Intestinal injury was induced in 7d-old WT or HO-1 heterozygous (Het) pups by p.o. formula-feeding every 4h for 24-78h and exposures to 5%O2. Controls remained breastfed. HO-1 was induced in WT pups by administering heme pre-injury induction. Lamina propria T cells were identified by flow cytometry. For adoptive transfer studies, WT splenic/thymic Tregs were injected i.p. into Het pups 12-24h pre-induction.ResultsHet mice showed increased intestinal injury and decreased Treg/Teff ratios. Genes for pattern recognition (TLR4, C-reactive protein, MyD88) and neutrophil recruitment increased in Het pups after NEC induction. Inducing intestinal HO-1 decreased NEC scores and incidence, and increased Treg/Teff ratios. Moreover, adoptive transfer of Tregs from WT to Het pps decreased NEC scores and incidence and restored Treg/Teff ratios.ConclusionsHO-1 can change Treg proportions in the lamina propria of young mice under inflammatory conditions, which might, in part, confer partial intestinal protection.Pediatric Research (2015); doi:10.1038/pr.2015.22.
    Pediatric Research 02/2015;
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    ABSTRACT: Background Placental lesions are associated with neurological morbidity but the mechanism leading to morbidity is unclear. To provide insight into such a possible mechanism we determined whether placental lesions were associated with regional cerebral tissue oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) in preterm infants during their first five days after birth. We hypothesized that as a result of cerebral hypoperfusion, regional cerebral tissue oxygen saturation would be lower and fractional tissue oxygen extraction would be higher.MethodA prospective, observational study of 42 preterm infants (GA <32wk). The infants' placentas were examined for histopathology. We measured rcSO2 and transcutaneous arterial oxygen saturation on days one to five. FTOE was calculated as FTOE = (transcutaneous arterial oxygen saturation - rcSO2)/transcutaneous arterial oxygen saturation.ResultsOnly three placentas showed no pathology. Ascending intrauterine infection (n=16) was associated with lower rcSO2 and higher FTOE values on days two, three, and four (P≤05). Other placental lesions were not associated with rcSO2 and FTOE.Conclusion Ascending intrauterine infection is associated with lower rcSO2, and higher FTOE shortly after birth. The effect it has on cerebral oxygenation might be the mechanism leading to neurodevelopmental problems.Pediatric Research (2015); doi:10.1038/pr.2015.20.
    Pediatric Research 02/2015;
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    ABSTRACT: Background The study aims to describe heart rate variability (HRV) in neonatal hypoxic ischaemic encephalopathy (HIE) and correlate HRV with electroencephalographic (EEG) grade of HIE and neurodevelopmental outcome.Methods Multi-channel EEG and electrocardiography (ECG) were assessed at 12-48 hours after birth in healthy and encephalopathic full-term neonates. EEGs were graded (normal, mild, moderate, and severe). Neurodevelopmental outcome was assessed at two-years of age. Seven HRV features were calculated using normalised-RR (NN) interval. The correlation of these features with EEG grade and outcome were measured using Spearman's correlation coefficient.ResultsHRV was significantly associated with HIE severity (p<0.05): standard deviation of NN interval (SDNN) (r=-0.62), triangular interpolation of NN interval histogram (TINN) (r=-0.65), mean NN interval (r=-0.48), and the very low frequency (VLF) (r=-0.60), low frequency (LF) (r=-0.67) and high frequency (HF) components of the NN interval (r=-0.60). SDNN at 24 and 48 hours were significantly associated (p<0.05) with neurodevelopmental outcome (r= -0.41 and -0.54, respectively).ConclusionsHRV is associated with EEG grade of HIE and neurodevelopmental outcome. HRV has potential as a prognostic tool to complement EEG.Pediatric Research (2015); doi:10.1038/pr.2015.28.
    Pediatric Research 02/2015;
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    ABSTRACT: Background Necrotizing enterocolitis (NEC), a common intestinal disease affecting premature infants, is a major cause of morbidity and mortality. Previous reports indicate an up regulation of intestinal Matrix Metalloproteinases (MMPs) activity that may play key roles on the higher permeability of the intestinal barrier, typical to NEC. Recently, TIMP-1, a natural inhibitor of MMP's, was found to be over expressed in preterm human breast milk (HBM). Previous studies have shown that infants fed with HBM have a significant reduction in the incidence of NEC.The aim of the present study was to investigate the possible role that TIMP-1 may play on the maintenance of tight junctions and therefore the gut barrier integrity.Methods Timp-1 treated Caco-2 intestinal cells were tested for MMP-2 enzymatic activity and cell junction integrity.ResultsTIMP-1 inhibited MMP-2 activity, induced a significant increase in the expression of occludin but not of claudin-4. TIMP-1 did not affect apoptosis.Conclusions One of the putative mechanisms associated with HBM protection against NEC is mediated by TIMP-1, which down regulates MMP-2 activity, inhibits the degradation of occludin and preserves tight junctions and gut barrier integrity.Pediatric Research (2015); doi:10.1038/pr.2015.26.
    Pediatric Research 02/2015;
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    ABSTRACT: Background Auditory event-related potentials (AERP) are neurophysiological correlates of sound perception and cognitive processes. Our aim was to study in very preterm born children at preschool age if AERP correlate with cognitive outcome.Methods Seventy children (mean±SD gestational age 27.4±1.9 weeks, birth weight 996±288 g) were investigated at age 4.3-5.3 years with psychological testing (WPPSI-R, four subtests of NEPSY). EEG was recorded while they listened to a repeated standard tone, randomly replaced by one of three deviants. Latencies and amplitudes for AERP components and mean amplitudes in successive 50-ms AERP time windows were measured.ResultsBetter cognitive test results and higher gestational age correlated with shorter P1 latencies and more positive mean amplitudes 150-500 ms after stimulus change onset. Neonatal brain damage was associated with a negative displacement of AERP curves. Neonatal morbidity had an impact on earlier time windows while gestational age and brain damage on both early and later time windows.ConclusionsAERP measures were associated with cognitive outcome. Neonatal morbidity mainly affects early cortical auditory encoding, while immaturity and brain damage additionally influence higher cortical functions of auditory perception and distraction. Perinatal auditory environment might play a role in development of auditory processing.Pediatric Research (2015); doi:10.1038/pr.2015.7.
    Pediatric Research 02/2015;
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    ABSTRACT: Background:Patients with cystic fibrosis (CF) are at increased risk of inspiratory muscle fatigue and respiratory failure. The time constant (τ) of the inspiratory muscle relaxation is a simple bedside test of muscle fatigue. We have compared patients with CF and healthy controls regarding τ and hypothesized that it is negatively associated with severity of lower airway obstruction.Methods:For this cross-sectional study, τ after maximal inspiration and spirometric indices (Forced Expiratory Volume in 1 second (FEV1) and Forced Vital Capacity (FVC)) were measured.Results:Fifty-three CF patients (median age 14 years (interquartile range: 11-19.5)) and 53 age- and sex-matched healthy control subjects (14 years (11-19.5)) were recruited. Application of a general linear model revealed that health status (CF vs. non-CF) had a significant effect on τ (p<0.001), but age group and the interaction of age group with health status did not have significant effects on τ (p=0.10 and p=0.71, respectively). Participants with CF had significantly higher τ (253 (188-406)) than control subjects (117(81-185)) (p<0.001) and τ was negatively related to FEV1 (r=-0.205; p=0.031) and FVC (r=-0.294; p=0.002).Conclusion:Patients with CF have higher τ than healthy controls but the correlation of τ with expiratory flow function is modest.Pediatric Research (2015); doi:10.1038/pr.2015.2.
    Pediatric Research 02/2015;
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    ABSTRACT: Background Vascular endothelial growth factor (VEGF), a well-characterized regulator of angiogenesis, has been mechanistically implicated in retinal neovascularization and in the pathogenesis of ROP. However, the ontogeny of VEGF expression in the human fetal retina is not well known. Because retinal vasculature grows with gestational maturation, we hypothesized that VEGF expression also increases in the midgestation human fetal eye as a function of gestational age.Methods To identify changes in VEGF gene expression during normal human development, we measured VEGF mRNA by quantitative PCR and measured VEGF protein by ELISA and western blots in 10-24 week gestation fetal vitreous, retina, and serum.ResultsVEGF mRNA expression in the retina increased with gestational age. VEGF isoform A, particularly its VEGF121 splice variant, contributed to this positive correlation. Consistent with these findings, we detected increasing VEGF121 protein concentrations in vitreous humor from fetuses of 10-24 weeks gestation, while VEGF concentrations decreased in fetal serum.ConclusionsVEGF121 mRNA and protein concentrations increase with increasing gestational age in the developing human retina. We speculate that VEGF plays an important role in normal retinal vascular development, and that preterm delivery affects production of this vascular growth factor.Pediatric Research (2015); doi:10.1038/pr.2015.15.
    Pediatric Research 01/2015;
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    ABSTRACT: Background Periventricular leukomalacia (PVL) is a major form of preterm brain injury. Na(+)-K(+)-Cl(-) 1 cotransporter (NKCC1) expression on neurons and astrocytes is developmentally regulated and mediates Cl(-) reversal potential. We hypothesized NKCC1 is highly expressed on oligodendrocytes (OLs) and increases vulnerability to hypoxia-ischemia (HI) mediated white matter injury, and that the NKCC1 inhibitor bumetanide would be protective in a rodent PVL model.Methods Immunohistochemistry in Long-Evans rats and PLP-EGFP transgenic mice was used to establish cell-specific expression of NKCC1 in the immature rodent brain. HI was induced on postnatal day 6 (P6) in rats and the protective efficacy of bumetanide (0.3 mg/kg/i.p. q12h x 60h) established.ResultsNKCC1 was expressed on OLs and subplate neurons through the first two postnatal weeks, peaking in white matter and the subplate between P3-7. Following HI, NKCC1 is expressed on OLs and neurons. Bumetanide treatment significantly attenuates myelin basic protein loss and neuronal degeneration 7d post-HI.Conclusions Presence and relative overexpression of NKCC1 in rodent cerebral cortex coincides with a period of developmental vulnerability to HI white matter injury in the immature prenatal brain. The protective efficacy of bumetanide in this model of preterm brain injury suggests Cl(-)transport is a factor in PVL and that its inhibition may have clinical application in premature human infants.Pediatric Research (2015); doi:10.1038/pr.2015.9.
    Pediatric Research 01/2015;
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    ABSTRACT: Background Etiology and pathogenesis of bronchial asthma remain unclear. This study is to investigate risk factors related to bronchial asthma onset in children from genetics and immunology and preliminarily reveal pathogenesis of bronchial asthma in children.Methods Real-time quantification PCR was adopted to detect expression level of TRPV1 gene and mRNA and ELISA method to the total IgE level and levels of IL-4, IL-5 and IFN-γ in serum in peripheral venous blood for children in two groups. Logistic regression analysis was applied to analyze the most essential factors inducing bronchial asthma in children.ResultsmRNA level of TRPV1 in peripheral blood in case group was higher than that in control group (p<0.01). Levels of IL-4, IL-5 and EOS in serum in case group were markedly higher than those in control group (p<0.01), while IFN-γ level was lower than that in control group (p<0.01). Results of logistic regression analysis indicated that TRPV1 expression level, IL-4 level and rs4790522 site mutation were the main risk factors inducing bronchial asthma in children.Conclusions Levels of TRPV1 gene expression and Th1/Th2 cytokines have a close relationship with asthma onset in children, which provides theoretical evidences for molecular targeted treatment in children with bronchial asthma.Pediatric Research (2015); doi:10.1038/pr.2015.11.
    Pediatric Research 01/2015;
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    ABSTRACT: Background Kawasaki disease (KD) is an acute febrile illness associated with the development of vasculitis. Administration of intravenous immunoglobulin (IVIG) is the standard treatment for KD. However, IVIG treatment is not effective in approximately 15% of children with KD. Some reports have presented evidence of immunological responses in IVIG-resistant KD patients. We assessed the possibility that T cell activation is a contributing mechanism underlying this phenomenon.Methods We analyzed human leukocyte antigen-DR (HLA-DR) expression on peripheral blood CD4(+) and CD8(+) T cells in 82 children with KD who were admitted to the hospital between October 2007 and February 2012. We compared the percentages of HLA-DR(+) T cells among the CD4(+) T cell and CD8(+) T cell populations for the IVIG-effective and IVIG-resistant groups.ResultsAmong the 82 subjects, 51 had IVIG-effective KD and 31 children had IVIG-resistant KD. The percentages of HLA-DR(+) T cells among the CD4(+) T cell and CD8(+) T cell populations in the IVIG-effective group were significantly lower than those in the IVIG-resistant group.Conclusions Our results suggest that increased T cell HLA-DR expression is associated with IVIG-resistance in KD patients, indicating that HLA-DR expression would be a useful tool for predicting IVIG responsiveness during KD pathogenesis.Pediatric Research (2015); doi:10.1038/pr.2015.12.
    Pediatric Research 01/2015;
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    ABSTRACT: Background Overexpression of connective tissue growth factor (CTGF) in alveolar type II epithelial (AT II) cells disrupts alveolar structure, causes interstitial fibrosis, and upregulates integrin-linked kinase (ILK). Whether CTGF-ILK signaling induces epithelial to mesenchymal transition (EMT) in AT II cells is unknown.Methods Transgenic mice with targeted overexpression of CTGF in AT II cells were generated utilizing the surfactant protein C (SP-C) gene promoter and doxycycline-inducible system. AT II cells were isolated from 4 weeks old CTGF-overexpressing (CTGF+) mice and control littermates, and cultured on Matrigel. Cells were transfected with ILK siRNA, and cell morphology and expression of cell differentiation markers were analyzed.ResultsThe AT II cells from the control lungs grew in clusters and formed alveolar-like cysts and expressed SP-C. In contrast, the cells from CTGF+ lungs were spread and failed to form alveolar-like cysts. These cells expressed higher levels of CTGF, α-SMA, fibronectin and vimentin, the mesenchymal markers, suggesting EMT-like changes. Transfection with ILK siRNA not only dramatically attenuated ILK expression, but also decreased α-SMA expression as well as reversed cell morphological changes in CTGF+ AT II cells.Conclusions Overexpression of CTGF induces EMT in mouse primary AT II cells and this is mediated by ILK.Pediatric Research (2015); doi:10.1038/pr.2015.8.
    Pediatric Research 01/2015;
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    ABSTRACT: Background The prevalence of febrile seizures (FSs) and epilepsy are often reported to be higher in sub-Saharan Africa. Furthermore, several studies describe complex features of FSs as risk factors for the development of subsequent epilepsy.Methods During the period from 2002 to 2004 door-to-door studies with supplementary data collection were conducted in three different areas of Tanzania, examining the prevalence of FSs in 7,790 children between the age of 2 months and 7 years at the time of the interview. The information on the presence of FSs of 14,583 children, who at the time of the interview were younger than 15 years, was collected in order to describe reported seizures, if any.ResultsOverall, 160 children between 2 months and 7 years with a prevalence rate of 20.5/1,000 (95% CI: 17.5-23.9/1,000) met the criteria for FSs. The average age at onset was 2.2 (SD: 1.8) years and approximately 42% had complex FSs. Respiratory tract infections and malaria were the most frequent concomitant diseases.Conclusions Our findings do not confirm the assumption of an increased prevalence of FSs in sub-Saharan Africa. However, the elevated number of complex FSs emphasizes the necessity of more reliable studies about FSs and its consequences.Pediatric Research (2015); doi:10.1038/pr.2015.3.
    Pediatric Research 01/2015;
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    ABSTRACT: Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models.MethodsTNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR.ResultsL. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression.Conclusions The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression.Pediatric Research (2015); doi:10.1038/pr.2015.5.
    Pediatric Research 01/2015;
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    ABSTRACT: Background Pulmonary hypertension (PH) secondary to vascular remodeling contributes to poor outcomes in congenital diaphragmatic hernia (CDH), however mechanisms responsible are unknown. We hypothesized that pulmonary artery endothelial cell (PAEC) dysfunction contributes to smooth muscle cell (SMC) hyperplasia in experimental CDH.MethodsPAEC and SMC were isolated from fetal sheep with experimental CDH and controls. SMC growth was assessed alone and with SOD plus catalase and during co-culture with control or CDH PAEC with and without ET-1 siRNA transfection. ET-1 protein was measured in PAEC and PASMC lysates and supernatant. ROS production was measured in normal and CDH PAECs with and without ET-1 siRNA. PAEC growth and tube formation were measured with SOD plus catalase.ResultsCDH SMC growth was decreased and and increased with co-culture with CDH PAEC more than control PAEC. Treatment of CDH PAEC with SOD plus catalase or ET-1 siRNA prevented the increase in SMC growth seen with co-culture. ET-1 protein was increased in CDH PAEC and SMC. ROS production was increased in CDH PAEC and decreased with ET-1 SiRNA. SOD plus catalase restored CDH PAEC growth and tube formation.ConclusionsPAEC dysfunction in experimental CDH increases SMC proliferation via ET-1 induced ROS production by PAEC.Pediatric Research (2015); doi:10.1038/pr.2015.13.
    Pediatric Research 01/2015;
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    ABSTRACT: Background Donor pasteurized human milk (HM) serves as the best alternative for breast-feeding when availability of mother's milk is limited. Pasteurization is also applied to mother's own milk for very low birth weight infants, who are vulnerable to microbial infection. Whether pasteurization affects protein digestibility and therefore modulates the profile of bioactive peptides released from HM proteins by gastrointestinal digestion, has not been examined to date.MethodsHM with and without pasteurization (62.5 ºC for 30 min) were subjected to in vitro gastrointestinal digestion, followed by peptidomic analysis to compare the formation of bioactive peptides.ResultsSome of the bioactive peptides, such as caseinophosphopeptide homologues, a possible opioid peptide (or propeptide), and an antibacterial peptide, were present in undigested HM and showed resistance to in vitro digestion, suggesting that these peptides are likely to exert their bioactivities in the gastrointestinal lumen, or be stably transported to target organs. In vitro digestion of HM released a large variety of bioactive peptides such as angiotensin I-converting enzyme-inhibitory, anti-oxidative, and immuno-modulatory peptides. Bioactive peptides were released largely in the same manner with and without pasteurization.Conclusions Provision of pasteurized HM may be as beneficial as breast-feeding in terms of milk protein-derived bioactive peptides.Pediatric Research (2015); doi:10.1038/pr.2015.10.
    Pediatric Research 01/2015;
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    ABSTRACT: Background22q11.2 deletion syndrome (22q11.2DS) is a congenital multi-system anomaly characterized by typical facial features, palatal anomalies, congenital heart defects, hypocalcemia, immunodeficiency, cognitive and neuropsychiatric symptoms. The aim of our study was to investigate T and B lymphocyte characteristics associated with 22q11.2DS.Methods Seventy-five individuals with 22q11.2DS were tested for T and B lymphocytes by examination of T cell receptor rearrangement excision circles (TRECs) and the B cell Kappa-deleting recombination excision circles (KRECs), respectively.ResultsThe 22q11.2DS individuals displayed low levels of TRECs, while exhibiting normal levels of KRECs. There was a significant positive correlation between TREC and KREC in the 22q11.2DS group, but not in controls. Both TREC and KREC levels showed a significant decrease with age and only TREC was low in 22q11.2DS individuals with recurrent infections. No difference in TREC levels was found between 22q11.2DS individuals who underwent heart surgery (with or without thymectomy) and those who did not,.ConclusionsT cell immunodeficiency in 22q11.2DS includes low TREC levels which may contribute to recurrent infections in individuals with this syndrome. A correlation between T and B cell abnormalities in 22q11.2DS was identified. The B cell abnormalities could account for part of the immunological deficiency seen in 22q11.2DS.Pediatric Research (2015); doi:10.1038/pr.2015.14.
    Pediatric Research 01/2015;
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    ABSTRACT: Background Fetal growth restriction is the second leading cause of perinatal morbidity and mortality, and neonates with intra-uterine growth retardation (IUGR) have increased neurocognitive and neuropsychiatric morbidity. These neurocognitive impairments are mainly related to injury of the developing brain associated with IUGR. Growing evidence from preclinical models of brain injury in both adult and neonatal rodents supports the view that nitric oxide can promote neuroprotection.Methods In a model of IUGR induced by protracted gestational hypoxia leading to diffuse white matter injury, we subjected neonatal rats to low dose (5ppm) but long-lasting (7 days) exposure to inhaled NO (iNO). We used a combination of techniques, including immunohistochemistry, quantitative PCR and cognitive assessment, to assess neuroprotection.ResultsAntenatal hypoxia-induced IUGR was associated with severe neuroinflammation and delayed myelination. iNO exposure during the first postnatal week significantly attenuated cell death and microglial activation, enhanced oligodendroglial proliferation and finally improved myelination. Remarkably, iNO was associated with the specific upregulation of P27kip1, which initiates oligodendrocytic differentiation. Finally, iNO counteracted the deleterious effects of hypoxia on learning abilities.Conclusions This study provides new evidence that iNO could be effective in preventing brain damage and/or enhancing repair of the developing brain.Pediatric Research (2015); doi:10.1038/pr.2015.4.
    Pediatric Research 01/2015;