摘要:

In this study, we examined the effects of dexamethasone (DEX) on airway branching and subsequent lung maturation. DEX treatment of fetal rat lung explants was initiated during the early pseudoglandular stage of development. Day 14 fetal lung explants were cultured with and without DEX for 4 d. Explants treated with 10 nM or higher concentrations of DEX showed features of both distorted and accelerated maturation. DEX-treated lungs had growth retardation, distorted branching, dilated proximal tubules, and suppressed proliferation of epithelial cells of the distal tubules. Several biochemical and morphologic features of accelerated maturation were also observed:1) the epithelial cells lining the distal tubules (prospective respiratory airways) were generally cuboidal or flattened;2) the cuboidal cells often contained lamellar bodies and abundant glycogen;3) rudimentary septa and large airspace were present;4) mesenchymal tissue was attenuated and compressed between adjacent epithelial tubules;5) the distribution of SP-C mRNA in distal tubules was more mature, with individual and clusters of cells expressing SP-C transcripts; and6) the transcript levels of several genes related to epithelial growth [keratinocyte growth factor (KGF), KGF receptor, and hepatocyte growth factor receptor] and differentiation [surfactant proteins, SP-A, SP-B and SP-C and the Clara cell secretory protein, CC10] were precociously increased. These results show that DEX treatment of the lung during the early pseudoglandular stage accelerates the acquisition of several features of advanced maturation that normally accompany late stages of fetal development. We postulate that KGF mediates at least some effects of DEX on lung maturation and gene expression.Abbreviations: CC10,Clara cell 10-kD protein;DEX,dexamethasone;DMEM,Dulbecco's modified Eagle's medium;GR,glucocorticoid receptor;HGF,hepatocyte growth factor;KGF,keratinocyte growth factor;KGFR,KGF receptor;MET,HGF receptor;PFA,4% paraformaldehyde;TAC,triamcinolone acetonide.

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We have reported that dexamethasone (DEX) treatment of early embryonic rat lungs in culture induced features of both distorted and accelerated maturation. In this report, we investigated the effects of retinoids on normal and DEX-induced lung developmentin vitro. Lung maturation was assessed by examining the morphology and the expression of genes related to epithelial differentiation (surfactant proteins, SP-A, SP-B and SP-C and Clara cell protein, CC10) and growth [keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF)]. We cultured d 14 and 15 fetal rat lungs in the presence of DEX (1-1000 nM) and/or all-trans-retinoic acid (RA)(10-7-10-5M) for 4 d. RA at 10-6and 10-5M inhibited branching and dilated the distal tubules, and at 10-5M caused dilatation of the proximal tubules destined to form the trachea and the main bronchi. The adverse effects of DEX, such as distorted branching, tubular dilatation, and suppression of both lung growth and epithelial cell proliferation, were all prevented by RA. In addition, RA inhibited several features of DEX-induced accelerated maturation, such as: 1) the increased levels of SP-A, SP-B, and CC10 mRNAs; 2) the attenuation of mesenchymal tissue; and 3) the mature distribution of cells expressing SP-C mRNA. In contrast, RA potentiated the increase of KGF and decrease of HGF transcripts induced by DEX. In conclusion, the study shows antagonism by RA of DEX-induced effects on lung morphology and gene expression. We postulate that normal lung development requires a balanced action of endogenous retinoids and glucocorticoids.Abbreviations: CC10,Clara cell 10-kD protein;DEX,dexamethasone;HGF,hepatocyte growth factor;KGF,keratinocyte growth factor;PFA,4% paraformaldehyde;RA,all-trans-retinoic acid;RAR,RA receptor

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This study was designed to determine the effects of a membrane permeant phosphodiesterase-resistant analog of cGMP on lung liquid production and pulmonary blood flow at the time of birth. Experiments were performed on seven fetal sheep prepared for chronic measurements of lung liquid production (Jv), pulmonary blood flow (Qp) and pressure, as well as systemic pressure. Injection of either 8-bromo-cGMP or saline were made via a catheter inserted in the left pulmonary artery. Experiments consisted of 1 h of control, 1 h of infusion, and 2 h of recovery. Data were analyzed by ANOVA and Newman-Keuls test. After infusion of 8-bromo-cGMP, Jv was decreased by 70 and 44% from control in h 3 and 4, respectively. Qp was elevated by 100 mL/min in h 2 and 3 and continued to be elevated by 50 mL/min in h 4. Saline infused animals showed no significant changes in Qp and Jv. This study demonstrates that 8-bromo-cGMP decreases lung liquid production and increases pulmonary blood flow in near term fetal sheep. Although blood flow increased in h 2, lung liquid production did not decrease at this time, suggesting a time dissociation between changes in pulmonary blood flow and lung liquid production. Thus, it is possible that a common transduction pathway involving cGMP may be responsible for lung liquid reduction and elevation of pulmonary blood flow at birth. However, Qp and Jv may not be causally related.Abbreviations: Jv,net lung liquid production;Qp,pulmonary blood flow;EDRF,endothelium-derived relaxing factor;NO,nitric oxide;PVR,pulmonary vascular resistance;PAP,pulmonary arterial pressure;PG,prostaglandin

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Synchronized atrial contraction may be much more important in the newborn, who has a faster heart rate and a less compliant ventricle, than in the adult. We therefore investigated the extent by which synchronized atrioventricular contraction contributes to cardiac output and cardiac work in a neonatal circulation, and whether this effect can be fully explained by the Starling mechanism. In neonatal piglets, left ventricular pressure and volume(conductance catheter) were measured during atrial and ventricular pacing. By manipulating preload during atrial pacing, endsystolic pressure and volume, stroke work, and dP/dtmaxwere compared at the same end-diastolic volume as indices of contractility. Finally, end-diastolic pressure-volume relationships were assessed to investigate the validity of using end-diastolic pressure as an indicator of preload. We found a significant contribution of synchronized atrial contraction; cardiac output increased 27% when pacing mode was switched form ventricular to atrial. The mechanism by which this was achieved is entirely the enhancement of ventricular filling and thus the Starling effect; contractility was unaffected by pacing mode. This large and important effect can be explained by slowed relaxation (compared with the adult ventricle), which impairs passive filling during the ventricular relaxation phase, and makes active filling during atrial contraction more important. In addition, we found that the use of end-diastolic pressure as an indicator of preload, instead of end-diastolic volume, leads to serious misinterpretations, due to not only the nonlinearity of this relationship, but also the possible shifts in this relationship with certain interventions.

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Leptin is a 16-kD protein encoded by theob/ob(obesity) gene. In rodents it plays a role in obesity, diabetes, fertility, and neuroendocrine function. In humans serum concentrations of leptin correlate with total body fat in both adults and children. We measured cord blood leptin in 186 neonates that included 82 appropriate for gestational age (AGA), 47 large for gestational age (LGA), 20 infants of diabetic mothers, 52 preterm infants, and 15 intrauterine growth-retarded (IUGR) infants. There were 16 pairs of twins. The mothers of 17 preterm infants were treated with steroids before delivery. Leptin (mean ± SD) concentration in term, AGA infants (39.4 ± 1.1 wk) with birth weight (BW) of 3.2 ± 0.3 kg, body mass index (BMI) of 12.6 ± 1.1 was 4.01 ± 3.5 ng/mL. BW correlated with cord leptin (p= 0.002) in a multivariate analysis controlling for potential confounders. Both LGA infants and infants of diabetic mothers had higher cord leptin concentration 7.3 ± 3.8 and 6.1 ± 4.8 ng/mL, respectively, compared with AGA infants (p< 0.05). Preterm infants had a mean leptin level of 1.8 ± 0.97 ng/mL and a 3-fold elevation was seen if mothers received steroids antenatally (p= 0.006). IUGR infants had increased leptin (6.5 ± 3.9 ng/mL,p= 0.03). Concerning the twin pairs, the smaller had a higher leptin level compared with larger twin (4.1 ± 9.51versus2.8 ± 5.14,p= NS). Neonatal cord leptin concentrations correlate well with BW and BMI. No gender differences were found in cord blood leptin. Maternal obesity had no effect on cord leptin, whereas exogenous maternal steroids increased neonatal leptin concentrations.Abbreviations: GHB,glycosylated Hb;AGA,appropriate for gestational age;LGA,large for gestational age;IUGR,intrauterine growth retardation;BW,birth weight;BMI,body mass index

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The aim of the present study was to investigate possible long-term effects of postnatally administered oxytocin on weight gain, gastrointestinal hormone levels, and nociceptive thresholds in rats. For this purpose, s.c. daily injections of oxytocin (1 mg/kg) or saline (NaCl, 0.9%) were given to male and female rat pups on d 10-14 after birth. The animals were killed at the age of 60 or 94 d. Treatment with oxytocin resulted in higher body weight in males, 60 d after birth, and in females from d 60 and throughout the rest of the experiment, compared with controls. The higher body weight was due to an increased weight gain in oxytocin-treated rats, compared with controls, which was most pronounced between 40 and 60 d after birth. Oxytocin-treated male rats had increased circulating levels of cholecystokinin, a tendency to increased plasma levels of insulin (p= 0.066), and relatively more adipose tissue in the thigh and interscapular region, compared with controls. At the age of 60 d, oxytocin-treated female and male rats had a prolonged withdrawal latency when measured in the tail-flick test, compared with controls. This study shows that oxytocin can induce long-lasting changes in weight gain, hormone levels, and nociceptive thresholds, when administered postnatally, in female and male rats.Abbreviation: CCK,cholecystokinin

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The fetal liver is the main hematopoietic organ during intrauterine life. Morphometrical studies were performed on liver sections to detect changes occurring with intrauterine growth retardation and preeclampsia. Compared with the controls (n= 10), fetuses from preeclamptic mothers showed a severe reduction of erythroid cells by 60% on average (n= 18). Closer examination revealed that the erythroid cells at early stages of differentiation were more affected (80% reduction) than at later stages (55%). Seven out of 18 fetuses from preeclamptic mothers did not show growth retardation but exhibited severely reduced hepatic erythropoiesis. We suggest that the prime factor for impaired red blood cell production is preeclampsia itself rather than intrauterine growth retardation. Regulation of erythropoiesisin uteromight depend on the interaction of many hematopoietic growth factors, and preeclampsia might alter the balance. To test this notion, we quantitated erythropoietin in fetal blood and various cytokines in the amniotic fluid. An elevation of erythropoietin and interleukin (IL)-3 levels was seen in babies born under the conditions of preeclampsia, whereas the concentrations of granulocyte/macrophage-colony-stimulating factor (CSF), granulocyte-CSF, and IL-1β were reduced, and the levels of IL-6 and IL-8 remained constant. With preeclampsia, a discrepancy between elevation of erythrocyte numbers in peripheral blood and depression of hematopoiesis at the main production site, the fetal liver, is seen. Concomitantly, there is elevation of some but reduction of other hematopoietic cytokines. We envision that during the course of preeclampsia quantitation of hematopoietic growth factors might allow to predict the deterioration ofin uterolife conditions.Abbreviations: Epo,erythropoietin;G,granulocyte;GM,granuloctye/macrophage;CSF,colony-stimulating factor

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The objective of this study was to compare formula intake, the time of weaning, and growth in preterm infants (≤1750-g birth weight, ≤34-wk gestation) fed a standard term or preterm infant formula after initial hospital discharge. Infants were randomized at hospital discharge to be fed a preterm infant formula from discharge to 6 mo corrected age (group A), a term formula from discharge to 6 mo (group B), or the preterm formula (discharge to term) and the term formula (term to 6 mo (group C). Infants were seen biweekly(discharge to term) and monthly (term to 6 mo), when intake was measured and anthropometry and blood sampling were performed. The results were analyzed using ANOVA. Although nutrient intake was similar, at 6 mo girls were lighter(6829versus7280 g) and shorter (64.4versus66.0 cm) than boys (p< 0.05). Patient characteristics were similar between the treatment groups. Although the volume of intake differed (B > C> A;p< 0.001), energy intake was similar in the groups. Because of differences in formula composition, protein, calcium, and phosphorus intakes differed (B < C < A;p< 0.001). Lower protein intakes were related to lower blood urea nitrogen levels (B < C< A;p< 0.001). At 6 mo, infant boys in B and C were lighter(6933, 6660 < 7949 g), shorter (65.3, 64.9 < 67.1 cm), and had a smaller head circumference (43.7, 43.7 < 44.8 cm;p< 0.05) than infants in group A. Preterm infants were found to increase their volume of intake to compensate for differences in energy density between formulas. After hospital discharge, infant boys fed a preterm formula grew faster than infant girls fed a preterm formula or infant boys fed a term formula.Abbreviation: BUN,blood urea nitrogen

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Bile acid concentrations are elevated in the blood of neonates with cholestatic hepatobiliary disorders providing a possible means of screening for treatable conditions including biliary atresia. A method is described for the determination of concentrations of conjugated bile acids in dried blood spots using electrospray ionization mass spectrometry. Bile acids were eluted from the blood spots using methanol containing, as internal standards, the taurine and glycine conjugates of D4-chenodeoxycholic acid and D4-cholic acid. The samples were then reconstituted in acetonitrile/water and injected by autosampler into the electrospray source operating in negative ion mode. Optimal conditions were determined for both single quadrupole and tandem mass spectrometry analysis. Blood spot bile acid profiles were studied in two groups of infants (<1 y), a cholestatic group(conjugated bilirubin >25 μmol/L;n= 49), and a control group(n= 96). The best discrimination between the two groups was provided by measurements of taurodihydroxycholanoates (normal <5 μmol/L; cholestatic group 18-94 μmol/L) and glycodihydroxycholanoates (normal <5μmol/L; cholestatic group 11-66 μmol/L). The method can also be adapted to detect unusual bile acids which are diagnostic of inborn errors of bile acid synthesis and peroxisomal disorders. The method is fast, reliable, reproducible, and relatively cheap; however, much more work is required to determine whether it can be used for mass screening for cholestasis. It will be necessary to show that measurement of bile acid concentrations in blood spots obtained at 7-10 d can be used to detect infants who currently present with jaundice, pale stools, and dark urine during the first 6 mo of life.Abbreviations: ESI,electrospray ionization;MS,mass spectrometry;MS/MS,tandem mass spectrometry;GCD,glycochenodeoxycholic acid;GC,glycocholic acid;TCD,taurochenodeoxycholic acid;TC,taurocholic acid;D4-GCD,[2,2,4,4-D4]-glycochenodeoxycholic acid;D4-GC,[2,2,4,4-D4]-glycocholic acid;D4-TCD,[2,2,4,4-D4]-taurochenodeoxycholic acid;D4-TC,[2,2,4,4-D4]-taurocholic acid;EDC,1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Circular smooth muscle cells from the feline newborn antrum, unlike the adult, are unable to respond to myogenic agonists in the absence of extracellular calcium or to exogenous inositol 1,4,5-trisphosphate(IP3). This study examined the reasons behind the relative inaccessibility of intracellular calcium stores in the newborn period. IP3binding was determined in antral smooth muscle homogenates from adult cats and newborns by evaluating the competitive binding of D-myo-[3H]IP3and unlabeled IP3. Receptor density (Bmax) (fmol/mg of protein) and binding affinity(Kd) were determined. The Kdwas similar in adults (31 ± 4 nM) and newborns (28 ± 7 nM); however, the Bmaxwas markedly decreased in the newborn (647 ± 181.0 fmol/mg) compared with the adult (1755 ± 275 fmol/mg). In adult and newborn antral cells, thapsigargin, which causes a net release of Ca2+from intracellular stores by inhibiting Ca2+-ATPase-dependent re-uptake activity, caused an early contraction at 30 s that was maintained for at least 20 min. We conclude that, in the newborn, dynamic intracellular calcium stores are present in the smooth muscle of the feline antrum and that differences in accessibility of intracellular calcium stores may be related to changes in the release of calcium from IP3-sensitive stores.Abbreviation:IP3,inositol 1,4,5-trisphosphate

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID