Abstract:
BACKGROUND:The pathogenesis of BPD includes inflammation and oxidative stress in the immature lung. Corticosteroids improve respiratory status and outcome, but the optimal treatment regimen for benefit with low systemic effects is uncertain. METHODS:In a pilot dose escalation trial, we administered ≤5 daily doses of budesonide in surfactant to 24 intubated premature infants (Steroid And Surfactant in ELGANs (SASSIE)). Untargeted metabolomics was performed on dried blood spots using UPLC-MS/MS. Tracheal aspirate IL-8 concentration was determined as a measure of lung inflammation. RESULTS:Metabolomics data for 829 biochemicals were obtained on 121 blood samples over 96 h from 23 infants receiving 0.025, 0.05, or 0.1 mg budesonide/kg. Ninety metabolites were increased or decreased in a time- and dose-dependent manner at q ≤ 0.1 with overrepresentation in lipid and amino acid super pathways. Different dose response patterns occurred, with negative regulation associated with highest sensitivity to budesonide. Baseline levels of 22 regulated biochemicals correlated with lung inflammation (IL-8), with highest significance for sphingosine and thiamin. CONCLUSIONS:Numerous metabolic pathways are regulated in a dose-dependent manner by glucocorticoids, which apparently act via distinct mechanisms that impact dose sensitivity. The findings identify candidate blood biochemicals as biomarkers of lung inflammation and systemic responses to corticosteroids. IMPACT:Treatment of premature infants in respiratory failure with 0.1 mg/kg intra-tracheal budesonide in surfactant alters levels of ~11% of detected blood biochemicals in discrete time- and dose-dependent patterns. A subset of glucocorticoid-regulated biochemicals is associated with lung inflammatory status as assessed by lung fluid cytokine concentration. Lower doses of budesonide in surfactant than currently used may provide adequate anti-inflammatory responses in the lung with fewer systemic effects, improving the benefit:risk ratio.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Ballard PL,Torgerson D,Wadhawan R,Hudak ML,Weitkamp JH,Harris J,Asselin J,Chapin C,Ballard RA,McEvoy CTdoi
10.1038/s41390-020-01343-zsubject
Has Abstractpub_date
2021-01-19 00:00:00eissn
0031-3998issn
1530-0447pii
10.1038/s41390-020-01343-zpub_type
杂志文章abstract:BACKGROUND:Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants. MET...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/s41390-018-0182-x
更新日期:2019-09-01 00:00:00
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
更新日期:2020-01-01 00:00:00
abstract::New information is emerging concerning the influence of environmental factors (e.g., viruses, pollutants, nutrients) on fetal lung development and the prenatal modulation of cellular and molecular effectors essential to the control of airway function, which may shed new light into the pathogenesis of chronic obstructi...
journal_title:Pediatric research
pub_type: 杂志文章,评审
doi:10.1038/s41390-019-0657-4
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:A growing body of evidence defines inflammation as a hallmark feature of disease pathogenesis of Duchenne muscular dystrophy. To tailor potential immune modulatory interventions, a better understanding of immune dysregulation in Duchenne muscular dystrophy is needed. We now asked whether dystrophin deficienc...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/s41390-019-0427-3
更新日期:2019-08-01 00:00:00
abstract::WT1 is located on the short arm of human chromosome 11 and consists of 10 coding exons. Mutations of this gene have been reported to be the cause of Wilms' tumor, congenital male genitourinary malformations, and/or renal disorders. We describe here a novel WT1 gene mutation, i.e. a point mutation at intron 7 (+2) in b...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200109000-00008
更新日期:2001-09-01 00:00:00
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
更新日期:2004-04-01 00:00:00
abstract::The ontogenetic renal responsiveness to exogenous cortisol was examined in the chronically cannulated ovine fetus. The contribution of effects at proximal and distal tubule of the kidney were studied also. Cortisol (81.5 micrograms/h) was infused into immature ovine fetuses (mean gestational age -113.9 days) on five o...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198907000-00002
更新日期:1989-07-01 00:00:00
abstract::Gaucher disease, the most common of the sphingolipidoses, results from the inherited deficiency of the enzyme glucocerebrosidase (EC 3.2.1.45). Although type 2 (acute neuronopathic) Gaucher disease is associated with rapidly progressive and fatal neurologic deterioration, the pathophysiologic mechanisms leading to the...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200008000-00018
更新日期:2000-08-01 00:00:00
abstract::In Chinese children with steroid-resistant nephrotic syndrome (SRNS), it was reported that NPHS2 mutation was detected in 4.3%, which was lower than that in Caucasians (10-30%). However, there were no data on WT1 mutation in nephrotic syndrome (NS), especially in early-onset NS of Chinese children. Thus, a study, whic...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e3181e4c9e3
更新日期:2010-08-01 00:00:00
abstract::The major variation in effect between undiluted cystic fibrosis and heterozygote sera on rabbit tracheal epithelium was in terms of the time after exposure at which changes occurred. Exposure to both types of sera for 3 min caused release of goblet cell mucus and ciliary resorption possibly by apical swelling of colum...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198011000-00005
更新日期:1980-11-01 00:00:00
abstract::The aim of this study was to evaluate the changes in Doppler transmitral flow patterns during the 1st d of life. Doppler echocardiography of the ascending aorta and mitral valve was performed serially in 20 normal neonates at 2, 12, and 24 h of age. A computer-interfaced digitizer pad was used to measure the following...
journal_title:Pediatric research
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Naloxone has been shown to reverse the hemodynamic sequelae of experimental septic shock in adult animal models. Its effectiveness in the newborn has not been studied. To further investigate the efficacy of naloxone, we instrumented 18 piglets for continuous measurement of mean arterial pressure, mean pulmonary arteri...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198608000-00001
更新日期:1986-08-01 00:00:00
abstract::D-myo-Inositol 1,4,5-triphosphate (IP3) is a key second messenger in many cells, including macrophages, T and B cells, and neutrophils, in which it regulates free intracellular calcium ion levels. In human polymorphonuclear leukocytes the rise of intracellular [Ca2+] is the signal that activates a number of functions ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199510000-00015
更新日期:1995-10-01 00:00:00
abstract:BACKGROUND:Prematurity may influence the levels of amino acids, enzymes, and endocrine markers obtained through newborn screening. Identifying which analytes are the most affected by degree of prematurity could provide insight into how prematurity impacts metabolism. METHODS:Analytes from blood spots assayed by Newbor...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2013.212
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:General movements (GMs) in infants occur as fidgety movements (FMs) between postterm 9 and 20 weeks. We aimed to evaluate FMs and motor repertoire in infants with cystic fibrosis (CF) and their relation with clinical findings. METHODS:Demographic and clinical characteristics were recorded. FMs and motor rep...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/s41390-020-1082-4
更新日期:2020-07-27 00:00:00
abstract::High speed cinemicrographs reveal that the ciliary configuration and beat pattern of rabbit tracheal cilia differ significantly from classid descriptions, although the basic forward and return pattern is still observed. The tracheal cilia are short and stout (about 6 mum in length) and are of a slightly bent original ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-197602000-00014
更新日期:1976-02-01 00:00:00
abstract::We examined the long-term effects of dietary protein restriction during rat pregnancy on serum IGF-I, serum IGF binding proteins, and liver IGF-I gene expression during postnatal development. Pregnant Wistar rats were fed ad libitum throughout gestation a normal (20% casein diet; P20 controls) or a low (5% casein; P5)...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199604000-00015
更新日期:1996-04-01 00:00:00
abstract::Newborn rats exposed to 60% O(2) for 14 d demonstrated a bronchopulmonary dysplasia-like lung morphology and pulmonary hypertension. A 21-aminosteroid antioxidant, U74389G, attenuated both pulmonary hypertension and macrophage accumulation in the O(2)-exposed lungs. To determine whether macrophage accumulation played ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200108000-00003
更新日期:2001-08-01 00:00:00
abstract::A number of neuromuscular diseases are associated with molecular defects in the mitochondrial DNA (mtDNA). These include: 1) a missense mutation at nucleotide 11778 in the mtDNA of Leber's hereditary optic neuropathy patients; 2) a heterogeneous array of deletions in the mtDNA of ocular myopathy patients; and 3) small...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199011000-00023
更新日期:1990-11-01 00:00:00
abstract::Blood volume (BV), red cell mass (RCM; Cr-51) and plasma volume (125I-labeled albumin) were measured in 205 piglets from 28 litters shortly after birth. Spontaneous cord rupture in healthy piglets occurred during delivery (n = 25) or within 190 sec of birth (n = 82). Spontaneous and induced delay of cord rupture resul...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198101000-00013
更新日期:1981-01-01 00:00:00
abstract::Platelet volume was measured in 20 healthy children, 18 patients with acute idiopathic thrombocytopenic purpura (ITP), 24 patients with chronic ITP, 22 patients with aplastic anemia, and 17 patients with acute leukemia in childhood. The authors compared the platelet volume of these patients by use of peak platelet vol...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198002000-00013
更新日期:1980-02-01 00:00:00
abstract::Previous studies have demonstrated that myocardial function changes during mammalian perinatal development. The purpose of this study was to evaluate the subcellular basis underlying the slower relaxation in the developing heart by examining perinatal changes in sarcoplasmic reticulum (SR) function, and in SR Ca2+ pum...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199205000-00012
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND:Kawasaki disease (KD) is the most common systemic vasculitis syndrome primarily affecting medium-sized arteries, particularly the coronary arteries. Though KD may be associated with immunological problems, the involvement of microRNAs (miRs) has not been fully described. METHODS:We enrolled 23 KD patients a...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2016.93
更新日期:2016-09-01 00:00:00
abstract::Astrocyte end-feet ensheathe blood vessels in the brain and are believed to provide structural integrity to the cerebral vasculature. We sought to determine in developing infants whether the coverage of blood vessels by astrocyte end-feet is decreased in germinal matrix (GM) compared with cerebral cortex and white mat...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.pdr.0000214975.85311.9c
更新日期:2006-05-01 00:00:00
abstract::Groups of newborn rats were transthoracically inoculated with 1 X 10(6) type III group B streptococci/g body wt, either alone or in combination with 1.5 microgram/g body wt of type-specific antibody derived from hybridoma cell lines. Ninety-four percent of the animals who received bacteria alone died. In contrast, non...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198310000-00005
更新日期:1983-10-01 00:00:00
abstract::Deficient quantity of amniotic fluid causes fetal guinea pig lung hypoplasia. Oligohydramnios that lasts only 5 days in early gestation is sufficient to reduce fetal lung growth significantly. We quantitated lung structural alterations at 50 days gestation (term is 67 days) of fetal guinea pigs whose amniotic fluid wa...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198610000-00013
更新日期:1986-10-01 00:00:00
abstract:BACKGROUND:Adolescents born preterm have altered hypothalamic-pituitary-adrenal axis function with a blunted cortisol stress response, however, the influences of intrauterine growth restriction and race are unclear. METHODS:We measured salivary cortisol before and 20 min after a maximal-exercise stress test and calcul...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/s41390-019-0682-3
更新日期:2020-05-01 00:00:00
abstract::Human Bifidobacterium sp strain bifidum (B. bifidum) was administered to BALB/c lactating mice (n = 58) and their litters (n = 327 pups) to evaluate the ingested strain's adherent properties and ability to inhibit murine rotavirus (MRV) infection. ELISA and anaerobic bacteriologic techniques were used to measure MRV s...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199406000-00014
更新日期:1994-06-01 00:00:00
abstract:OBJECTIVES:(1) Examine associations of a branched-chain amino acid (BCAA) metabolite pattern with metabolic risk across adolescence; (2) use Least Absolute Shrinkage and Selection Operator (LASSO) to identify novel metabolites of metabolic risk. METHODS:We used linear regression to examine associations of a BCAA score...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/s41390-018-0195-5
更新日期:2019-02-01 00:00:00
abstract::We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HCl-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198806000-00023
更新日期:1988-06-01 00:00:00