Placental transfer and fetal metabolism of zidovudine in the baboon.

Abstract:

:Zidovudine (azidothymidine, AZT) is used in pregnancy to reduce mother to infant transmission of HIV. Understanding the disposition of AZT in the fetus is necessary to optimize therapeutic regimens directed toward the fetus. Recent studies in primates found similar steady-state levels of the glucuronide metabolite of AZT (AZT-glu) in the fetus to those in the mother, raising the question of whether the metabolite was of fetal or maternal origin. The objective of this study was to determine whether glucuronidation occurred in the fetal compartment and to quantify the placental and fetal clearances of AZT using the two-compartment model at steady state. Steady-state concentrations were obtained after paired maternal and fetal infusions of AZT in chronically catheterized pregnant baboons. During maternal infusion, the mean (+/-SE) fetal to maternal ratio of AZT was < 1 (0.84 +/- 0.06, p < 0.02), suggesting clearance of AZT in the fetus. Mean total maternal clearance of AZT was 725 +/- 49 mL/min and placental clearance was 36 +/- 4 mL/min, or approximately 5% of maternal clearance. Fetal clearance of AZT was estimated at approximately 15% of placental clearance. This suggests fetal nonplacental clearance is minimal compared with that in the mother, but does not preclude the fetus from actively contributing to the metabolite in the fetal circulation. During infusion of AZT to the fetus, the concentration of AZT-glu in the fetus was 7.0 +/- 0.8 times that in the mother. This is compelling evidence that glucuronide can be formed in the fetal compartment. Thus, fetal metabolism has an impact on the concentration of both AZT and AZT-glu in the fetal circulation.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Garland M,Szeto HH,Daniel SS,Tropper PJ,Myers MM,Stark RI

doi

10.1203/00006450-199807000-00008

subject

Has Abstract

pub_date

1998-07-01 00:00:00

pages

47-53

issue

1

eissn

0031-3998

issn

1530-0447

journal_volume

44

pub_type

杂志文章
  • Neonatal stress: effects of hypoglycemia and hypoxia on adrenal tyrosine hydroxylase gene expression.

    abstract::Catecholamines (CA) are released from and resynthesized in the adrenal medulla in response to stress. In the mature animal, stimulus-secretion-synthesis coupling occurs through transsynaptic (neuronal) activity. In contrast, in the immature animal, before functional adrenal innervation, certain stressors (hypoglycemia...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199412000-00006

    authors: DeCristofaro JD,LaGamma EF

    更新日期:1994-12-01 00:00:00

  • Detection of a transcript abnormality in mRNA of the SLC12A3 gene extracted from urinary sediment cells of a patient with Gitelman's syndrome.

    abstract::To date, many mutations, including intronic nucleotide changes, in the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT) have been reported in Gitelman's syndrome (GS) patients. However, it has not been clarified whether intronic nucleotide changes affect mRNA content. Since mRNA analys...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/pdr.0b013e318031935a

    authors: Kaito H,Nozu K,Fu XJ,Kamioka I,Fujita T,Kanda K,Krol RP,Suminaga R,Ishida A,Iijima K,Matsuo M

    更新日期:2007-04-01 00:00:00

  • Development of blood coagulation--a fetal lamb model.

    abstract::To study the normal development of blood coagulation factor activities in a growing fetus while avoiding the effects of labor and delivery, a chronic fetal lamb model was developed in which serial blood samples from 10 fetuses were studied during the third trimester of pregnancy and 24 hr after birth. Under operating ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198107000-00014

    authors: Kisker CT,Robillard JE,Clarke WR

    更新日期:1981-07-01 00:00:00

  • Effect of Kawasaki disease on migration of human umbilical vein endothelial cells.

    abstract::Kawasaki disease, which is characterized by systemic vasculitis causing coronary arterial involvement in childhood, shows a variety of immunoregulatory abnormalities. Especially the direct or indirect deleterious effects on endothelial cells of cytokines and anti-endothelial cell antibodies (AECA) are considered to be...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199510000-00005

    authors: Sakata K,Kita M,Imanishi J,Onouchi Z,Liu Y,Mitsui Y

    更新日期:1995-10-01 00:00:00

  • Mouse model of mevalonate kinase deficiency: comparison of cytokine and chemokine profile with that of human patients.

    abstract:BACKGROUND:Mevalonate kinase deficiency (MKD) is a rare genetic autoinflammatory disease caused by blocking of the enzyme mevalonate kinase in the pathway of cholesterol and isoprenoids. The pathogenic mechanism originating an immune response in MKD patients has not been clearly understood. METHODS:We investigated the...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2013.96

    authors: Marcuzzi A,Zanin V,Kleiner G,Monasta L,Crovella S

    更新日期:2013-09-01 00:00:00

  • In vitro studies of effects of light and riboflavin on DNA and HeLa cells.

    abstract::The widespread use of phototherapy for neonatal hyperbilirubinemia has caused some concern since substances other than bilirubin may be photoactivated. The toxic properties of these photoactivated substances might prove to be more harmful to the neonatal infant than bilirubin. The purpose of the present study was to i...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-197503000-00009

    authors: Speck WT,Chen CC,Rosenkranz HS

    更新日期:1975-03-01 00:00:00

  • Intellectual, neurologic, and neuropsychologic outcome in untreated subjects with nonphenylketonuria hyperphenylalaninemia. German Collaborative Study on Phenylketonuria.

    abstract::Based on the serum phenylalanine levels under free diet patients with hyperphenylalaninemia are classified as "classical" (>1200 micromol/L), "mild" (600-1200 micromol/L), or "non-phenylketonuria (PKU)-hyperphenylalaninemia" (<600 micromol/L). Recent studies revealed intellectual, neurologic, and neuropsychologic defi...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199709000-00020

    authors: Weglage J,Ullrich K,Pietsch M,Fünders B,Güttler F,Harms E

    更新日期:1997-09-01 00:00:00

  • Physical activity and sedentary levels in children with juvenile idiopathic arthritis and inflammatory bowel disease. A systematic review and meta-analysis.

    abstract:BACKGROUND:Physical activity (PA) is essential for children throughout their growth and maturation. It improves physiological and psychological health and limits the risk of developing metabolic disorders. However, some chronic physiological and metabolic diseases may lead to decreased PA. The diversity of outcomes in ...

    journal_title:Pediatric research

    pub_type: 杂志文章,meta分析

    doi:10.1038/s41390-019-0409-5

    authors: Bourdier P,Saidi O,Rochette E,Ratel S,Merlin E,Pereira B,Duché P

    更新日期:2019-08-01 00:00:00

  • Association of attention-deficit/hyperactivity disorder with diabetes: a population-based study.

    abstract:BACKGROUND:Cognitive impairment has been documented in adult diabetes but is unclear in pediatric diabetes. No study had been conducted to explore the relationship between attention-deficit/hyperactivity disorder (ADHD) and diabetes. Using a population-based data set, we aimed to examine the association between ADHD an...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2013.5

    authors: Chen HJ,Lee YJ,Yeh GC,Lin HC

    更新日期:2013-04-01 00:00:00

  • Cardiomyocyte regeneration from circulating bone marrow cells in mice.

    abstract::We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.PDR.0000078275.14079.77

    authors: Kuramochi Y,Fukazawa R,Migita M,Hayakawa J,Hayashida M,Uchikoba Y,Fukumi D,Shimada T,Ogawa S

    更新日期:2003-09-01 00:00:00

  • Inhibition of β-catenin signaling protects against CTGF-induced alveolar and vascular pathology in neonatal mouse lung.

    abstract:BACKGROUND:Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of premature infants. Connective tissue growth factor (CTGF) plays an important role in tissue development and remodeling. We have previously shown that targeted overexpression of CTGF in alveolar type II epithelial cells re...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2016.52

    authors: Rong M,Chen S,Zambrano R,Duncan MR,Grotendorst G,Wu S

    更新日期:2016-07-01 00:00:00

  • Glycolytic metabolism of neonatal mononuclear cells.

    abstract::The mononuclear cells of newborn infants compared to those of normal adults contain diminished activity of pyruvate kinase (PK) (14.9 +/- 1.2 vs. 22.3 +/- 1.3 mumol/10(10) cells/min) and phosphoglycerate kinase (PGK) (195 +/- 10 vs. 415 +/- 19). These deficiencies are accentuated in the cells of premature infants (4.9...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-197710000-00008

    authors: Das M,Klein W,Feig SA

    更新日期:1977-10-01 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

  • Ornithine decarboxylase and S-adenosyl methionine decarboxylase in skin fibroblasts of normal and cystic fibrosis patients.

    abstract::The key enzymes in the synthesis of the naturally occurring polyamines, ornithine decarboxylase (ODC) and S-adenosyl methionine (SAM) decarboxylase, were investigated during cell growth and aging in fibroblast cultures from normal patients and patients with cystic fibrosis. A linear correlation between increased S-ade...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-197703000-00009

    authors: Buehler B,Wright R,Schott S,Darby B,Rennert OM

    更新日期:1977-03-01 00:00:00

  • Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy.

    abstract::This patient presented on the first day of life with pronounced lactic acidosis with an elevated lactate/pyruvate ratio. Urine organic acids showed Krebs cycle metabolites and mildly elevated methylmalonate and methylcitrate. The acylcarnitine profile showed elevated propionylcarnitine and succinylcarnitine. Amino aci...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/PDR.0b013e3181e5c3a4

    authors: Van Hove JL,Saenz MS,Thomas JA,Gallagher RC,Lovell MA,Fenton LZ,Shanske S,Myers SM,Wanders RJ,Ruiter J,Turkenburg M,Waterham HR

    更新日期:2010-08-01 00:00:00

  • Chitosan enhances the in vitro surface activity of dilute lung surfactant preparations and resists albumin-induced inactivation.

    abstract::Chitosan is a natural, cationic polysaccharide derived from fully or partially deacetylated chitin. Chitosan is capable of inducing large phospholipid aggregates, closely resembling the function of nonionic polymers tested previously as additives to therapeutic lung surfactants. The effects of chitosan on improving th...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.pdr.0000227558.14024.57

    authors: Zuo YY,Alolabi H,Shafiei A,Kang N,Policova Z,Cox PN,Acosta E,Hair ML,Neumann AW

    更新日期:2006-08-01 00:00:00

  • Effect of ventilation on mechanical properties and pressure-flow relationships of immature airways.

    abstract::Ventilation of immature airways has been shown to result in pressure-induced deformation and alteration of mechanical properties. These changes in mechanical properties may alter the effect of compressive pressures on pressure-flow relationships. To test this hypothesis, unventilated (Group I, n = 8) and ventilated (g...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198805000-00017

    authors: Penn RB,Wolfson MR,Shaffer TH

    更新日期:1988-05-01 00:00:00

  • The relation of severe malnutrition in infancy to the intelligence of school children with differing life histories.

    abstract::The IQ's of Jamaican boys aged 6-10 were associated significantly with the presence or absence of severe malnutrition in infancy, with height at time of IQ testing, and with a measure of the boys' social background. A multiple correlation coefficient of 0.674 was obtained between IQ and the three factors. Social backg...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-197601000-00011

    authors: Richardson SA

    更新日期:1976-01-01 00:00:00

  • Utility of cytokines to predict neonatal sepsis.

    abstract:BACKGROUND:Sepsis is an important cause of neonatal morbidity and mortality worldwide. Diagnosis and treatment of neonatal sepsis relies on clinical judgment and interpretation of nonspecific laboratory tests. In a prospective cohort, we measured inflammatory cytokines as a potential biomarker for neonatal sepsis. MET...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2016.267

    authors: Ye Q,Du LZ,Shao WX,Shang SQ

    更新日期:2017-04-01 00:00:00

  • The effects of omega-3 fatty acid supplementation in pregnancy on maternal eicosanoid, cytokine, and chemokine secretion.

    abstract::The incidence of allergic diseases has increased, and a relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcomes in the child. The aim of this study was to determine the effects of omega (omega)-3 long...

    journal_title:Pediatric research

    pub_type: 杂志文章,随机对照试验

    doi:10.1203/PDR.0b013e3181aabd1c

    authors: Warstedt K,Furuhjelm C,Duchén K,Fälth-Magnusson K,Fagerås M

    更新日期:2009-08-01 00:00:00

  • Spontaneous gonadotropin and testosterone concentration profiles in prepubertal and pubertal boys: temporal relationship between luteinizing hormone and testosterone.

    abstract::To investigate the detailed pattern of change in circulating gonadotropin and testosterone concentrations around the onset of puberty and to determine the temporal relationship between the gonadotropin and testosterone secretion, plasma gonadotropin and testosterone were measured at 20-min intervals for 24 h in 21 nor...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199308000-00026

    authors: Goji K,Tanikaze S

    更新日期:1993-08-01 00:00:00

  • Fish oil supplementation in pregnancy modifies neonatal progenitors at birth in infants at risk of atopy.

    abstract::Dietary n-3 polyunsaturated fatty acids (PUFA) may represent a mode of allergy prevention. Cord blood (CB) CD34+ hemopoietic progenitors are altered in infants at risk of atopy. We therefore studied the effects of dietary n-3 PUFA supplementation during pregnancy on numbers and function of progenitors in neonates at h...

    journal_title:Pediatric research

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1203/01.PDR.0000148279.72611.1D

    authors: Denburg JA,Hatfield HM,Cyr MM,Hayes L,Holt PG,Sehmi R,Dunstan JA,Prescott SL

    更新日期:2005-02-01 00:00:00

  • In vivo study of phytanic acid alpha-oxidation in classic Refsum's disease and chondrodysplasia punctata.

    abstract::A series of in vivo experiments is described in which [1-13C]phytanic acid was given as an oral substrate to a healthy subject and two patients showing an impairment in phytanic acid degradation, one with Refsum's disease and one with chondrodysplasia punctata. After intake of the substrate by the control in a dose of...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199211000-00016

    authors: ten Brink HJ,Schor DS,Kok RM,Stellaard F,Kneer J,Poll-The BT,Saudubray JM,Jakobs C

    更新日期:1992-11-01 00:00:00

  • Bilirubin toxicity in a neuroblastoma cell line N-115: II. Delayed effects and recovery.

    abstract::Clinical studies have suggested that the early stages of bilirubin encephalopathy are reversible. These phenomena are investigated at the cellular level using the neuroblastoma cell line N-115 as a model system. To determine whether the cell line N-115 can recover from bilirubin toxicity, and whether the cellular func...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198904000-00012

    authors: Amit Y,Poznansky MJ,Schiff D

    更新日期:1989-04-01 00:00:00

  • Effect of acute polycythemia on newborn renal hemodynamics and function.

    abstract::The present study investigates the effects of polycythemia on renal hemodynamics and function in 15 anesthetized newborn dogs, 2-10 days of age. Microspheres were used to study renal blood flow. Experimental animals received an exchange transfusion with adult dog packed red blood cells resulting in an increase in hema...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198202000-00014

    authors: Kotagal UR,Kleinman LI

    更新日期:1982-02-01 00:00:00

  • Intranasal fluticasone furoate in pediatric allergic rhinitis: randomized controlled study.

    abstract:BACKGROUND:Intranasal corticosteroids are the most efficacious anti-inflammatory medications for allergic rhinitis (AR). However, the efficacy and safety of intranasal corticosteroids in children have not yet been subject to specific research in China. The aim of this study was to investigate the efficacy and safety of...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-020-01180-0

    authors: Zhang Y,Wei P,Chen B,Li X,Luo X,Chen X,Xiang M,Li L,Zhao S,Xiao X,Yang X,Chen J,Fu Y,Xiao S,Liu H,Cheng L,Yao H

    更新日期:2020-10-02 00:00:00

  • Early postnatal development in the rat is characterized by accumulation of highly unsaturated triacylglycerols.

    abstract::Our objective was to determine the quantitative changes of individual triacylglycerol (TG) species in liver and carcass during early postnatal growth. Pregnant rats were killed at d 21 of pregnancy, and neonatal rats were killed at d 3 or 9 after birth. Quantitative changes in fatty acids and TG species of fetal/neona...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199201000-00009

    authors: Chen ZY,Cunnane SC

    更新日期:1992-01-01 00:00:00

  • Impaired cerebral development in fetuses with congenital cardiovascular malformations: Is it the result of inadequate glucose supply?

    abstract::Cerebral development may be impaired in fetuses with congenital cardiovascular malformations, particularly hypoplastic left heart syndrome (HLHS) and aortopulmonary transposition (APT). The decreased cerebral arterial pusatility index observed in some of these fetuses led to the belief that cerebral vascular resistanc...

    journal_title:Pediatric research

    pub_type: 杂志文章,评审

    doi:10.1038/pr.2016.65

    authors: Rudolph AM

    更新日期:2016-08-01 00:00:00

  • Surface and cytoplasmic immunoglobulin expression in circulating B-lymphocytes in acute Kawasaki disease.

    abstract::Kawasaki disease (KD) is an acute vasculitis of young childhood predominantly affecting the coronary arteries. IgA plasma cells have been found to infiltrate vascular and nonvascular tissues in fatal acute KD. To determine whether IgA B-lymphocytes were increased in the peripheral blood of patients with KD, we perform...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-200110000-00019

    authors: Shingadia D,O'Gorman M,Rowley AH,Shulman ST

    更新日期:2001-10-01 00:00:00

  • Sensitization to cow's milk proteins during refeeding of guinea pigs recovering from polydeficient malnutrition.

    abstract::We have previously shown that milk sensitization aggravates intestinal dysfunction in the malnourished guinea pigs, suggesting that it may also impair the recovery from malnutrition. To test this hypothesis, the growing guinea pigs were malnourished by feeding only maize for 7 d and then were refed for 21 d with a bal...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199812000-00018

    authors: Darmon N,Abdoul E,Roucayrol AM,Blaton MA,Briend A,Desjeux JF,Heyman M

    更新日期:1998-12-01 00:00:00