摘要:

The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants <7 d old were randomized to be fed formulas containing linoleic acid (≈10% kcal) andα-linolenic acid (≈1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA+ DHA formula had levels of both LCP within ≈10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.Abbreviations: LCP,long chain polyunsaturated;SWI,Similac® with Iron;DHA,docosahexaenoic acid;AA,arachidonic acid;EPA,eicosapentaenoic acid;RBC,red blood cell;PC,phosphatidylcholine;PE,phosphatidylethanolamine;VEP,visual evoked potential;ANOVA,analysis of variance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We investigated the effect of streptozotocin-induced short-term maternal diabetes upon fetal rat myocardial and skeletal muscle glucose transporter Glut 1 (basal form) and Glut 4 (insulin-responsive form) protein concentrations by Western blot analysis. In the severely diabetic group(SEVERE-D,n= 17), a 3-fold increase in maternal and fetal glucose concentrations (p< 0.01) was associated with a 3-fold decline in maternal (p< 0.01) with no change in fetal insulin levels when compared with the streptozotocin-treated nondiabetic (n= 10) and vehicle-treated control (control,n= 14) groups. These changes in the SEVERE-D group when compared with controls were associated with a 30 and 65% decline, respectively, in fetal myocardial and skeletal muscle (forelimb and hind limb) Glut 1 protein concentrations. The fetal myocardium also demonstrated a 45% decline in Glut 4 protein levels. Fetal skeletal muscle Glut 4 protein, which was expressed only at very low levels in controls showed no change in SEVERE-D. Immunohistochemical analysis revealed a myocyte-plasma membrane association of Glut 1 and an intracellular Glut 4 distribution in the fetal myocardium and skeletal muscle. No Glut 1 immunoreactivity was noted in either the fetal myocardial or skeletal muscle perineural sheaths, blood vessels, or the entrapped fetal red blood cells. This subcellular localization pattern was unaltered in all three treatment groups. We conclude that maternal diabetes causing fetal hyperglycemia with normoinsulinemia suppresses fetal myocardial Glut 1 and Glut 4 and fetal skeletal muscle Glut 1. The decline in the plasma membrane associated Glut 1 concentrations may serve a protective function by reducing the glucose transport rate into fetal myocardial and skeletal muscle cells, which otherwise could be vulnerable to high circulating glucose. The in-utero maternal diabetes induced decrease in fetal myocardial intracellular-Glut 4 concentration could herald the emergence of insulin resistance.Abbreviations: Glut 1,glucose transporter isoform 1;Glut 4,glucose transporter isoform 4;SEVERE-D,streptozotocin-treated severely diabetic group;STZ-ND,streptozotocin-treated nondiabetic group;ANOVA,analysis of variance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Administration of glucocorticoids to neonates increases proximal tubule volume absorption by increasing glucose, bicarbonate, and amino acid transport. We have recently demonstrated that glucocorticoids may contribute to the maturational decrease in phosphate transport. This study examines the maturation of NaPi-6 [the regulated proximal tubule sodium-inorganic phosphate (Na-Pi) transporter] mRNA and protein abundance and the mechanism for the decrease in phosphate transport by glucocorticoids. Weaned young rabbits (5 wk) had a 2-fold greater brush border membrane NaPi-6 protein abundance than that measured in adults. Renal cortical NaPi-6 mRNA abundance was comparable in neonates (less than 10 d of age) and adults. Renal brush border membrane vesicles from dexamethasone-treated neonatal rabbits (10 μg/100 g of body weight for 4 d) had a lower rate of Na-Pitransport than vehicle-treated controls (46.8 ± 6.5versus71.0 ± 9.0 pmol32P/10 s/mg of protein,p< 0.05). Abundance of NaPi-6 protein in brush border membrane vesicles was 3-fold lower in newborn rabbits treated with pharmacologic doses of dexamethasone than in vehicle-treated controls. NaPi-6 mRNA abundance was the same in both groups. NaPi-1, a brush border membrane phosphate transporter which is also an anion channel, mRNA, and protein abundance was not affected by glucocorticoids. These data demonstrate that there is a maturational decrease in NaPi-6 protein abundance and that glucocorticoids decrease neonatal phosphate transport, at least in part, by reducing the number of Na-Pitransporters.Abbreviations: Pi,inorganic phosphate;BBM,brush border membrane;BBMV,brush border membrane vesicle;NaPi-1,rabbit type I Na-Pitransporter;NaPi-6,rabbit type II Na-Pitransporter;NHE,sodium-hydrogen exchanger

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Aldosterone, the most important mineralocorticoid, regulates electrolyte excretion and intravascular volume mainly through its effects on renal distal tubules and cortical collecting ducts, where it acts to increase sodium resorption from and potassium excretion into the urine. Excess secretion of aldosterone or other mineralocorticoids, or abnormal sensitivity to mineralocorticoids, may result in hypokalemia, suppressed plasma renin activity, and hypertension. The syndrome of apparent mineralocorticoid excess(AME) is an inherited form of hypertension in which 11β-hydroxysteroid dehydrogenase (11β-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, cortisone. Because mineralocorticoid receptors themselves have similar affinities for cortisol and aldosterone, it is hypothesized that the deficiency allows these receptors to be occupied by cortisol, which normally circulates at levels far higher than those of aldosterone. We cloned cDNA and genes encoding two isozymes of 11β-HSD. The liver (L) or type 1 isozyme has relatively low affinity for steroids, is expressed at high levels in the liver but poorly in the kidney, and is not defective in AME. The kidney (K) or type 2 isozyme has high steroid affinity and is expressed at high levels in the kidney and placenta. Mutations in the gene for the latter isozyme have been detected in all kindreds with AME. Moreover, thein vitroenzymatic activity conferred by each mutation is strongly correlated with the ratio of cortisol to cortisone metabolites in the urine [tetrahydrocortisone (THF) + allo-THF]/THE. This suggests that the biochemical phenotype of AME is largely determined by genotype.Abbreviations: AME,apparent mineralocorticoid excess;HSD,hydroxysteroid dehydrogenase;THF,tetrahydrocortisol;THE,tetrahydrocortisone

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Growth of 92 Finnish patients with 21-hydroxylase deficiency (21-OHD) was analyzed retrospectively to study growth both before the diagnosis and during glucocorticoid substitution therapy. The patients were divided into two groups: those diagnosed at infancy (56 patients) and those diagnosed after the age of 1 y (36 patients). Birth lengths of those boys and girls diagnosed at infancy were greater than the national mean birth lengths (p< 0.001). Mean relative length diminished from +0.8 SD score (SDS) at birth to-1.0 SDS by the age of 1 y. Adult height was -1.0 SDS (159.9 cm) for women and-0.8 SDS (173.6 cm) for men. The difference from national mean height was significant only for women (p= 0.026). Mean relative weight during childhood correlated negatively with adult stature (r= -0.620;p= 0.006). In the group of children diagnosed later in their childhood, growth was already accelerated at infancy from +0.2 SDS at birth to+0.7 SDS by the age of 1 y (p= 0.023). The final height of girls diagnosed later in childhood was within normal limits (-0.5 SDS; 162.1 cm), whereas it was low in the corresponding group of boys (-2.1 SDS; 165.3 cm). Our data show increased mean birth length in babies with early diagnosis of 21-OHD and growth acceleration at infancy in children diagnosed later in their childhood, reflecting the growth accelerating effect of adrenal hyperandrogenism early during fetal life and infancy. To improve final height in patients with 21-OHD, lower doses of hydrocortisone should be used at infancy, and special attention should be paid to boys diagnosed later in childhood.Abbreviations: 21-OHD,21-hydroxylase deficiency;SDS,SD score;PSEH,parent-specific expected height SD score

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Circulating glucocorticoids play a role during the immediate postnatal period in adapting the neonate to extrauterine life and are also thought to influence tissue development and function in the later postnatal period. In the present study we have used a rat model to test whether birth by cesarean section (C-section), either alone or with an added period of acute anoxia, affects the developmental profile of basal corticosterone secretion during the first 5 wk of life. Plasma levels of total corticosterone and of corticosteroid-binding globulin were measured at various times after birth in rats born vaginally, by C-section, or by C-section with 15 min of added anoxia. These measures allowed for calculation of levels of free, biologically active, corticosterone. Under all conditions, total corticosterone appeared to accurately reflect levels of free corticosterone. Plasma corticosterone levels measured immediately (<5 min) after birth were similar in male rat pups born vaginally, by C-section, or by C-section with added anoxia, whereas female pups born by C-section showed a significant increase in free corticosterone at birth, in comparison with vaginally born females. Both male and female animals born by C-section showed a reduction in plasma corticosterone at 1 h (male: 31% of control,p< 0.01; female: 45% of control,p< 0.05) and at 7 d (male: 61% of control,p< 0.01; female: 55% of control,p< 0.05) after birth, in comparison with vaginally born controls. In animals born by C-section with added anoxia, significant reductions in plasma corticosterone were observed for males at 1 h (58% of control;p< 0.05) and for females at 7 d (62% of control;p< 0.05) after birth. At 14 d of age, corticosterone levels were higher in male rats born by C-section either with (227% of control;p< 0.05) or without (239% of control;p< 0.05) added anoxia, in comparison with vaginally born controls. Thus C-section birth produces an early rise in plasma corticosterone on d 14 away from the low values associated with the adrenal quiescent period in the first 1-2 wk in the rat. By 35 d of age, there were no differences in plasma corticosterone attributable to C-section birth and/or acute birth anoxia, in either male or female rats. It is concluded that, in a rat model, birth by C-section has significant effects on the profile of plasma corticosterone during the early weeks of development, a period thought to be critical for effects of corticosteroids on developing tissues. Because the rat at birth is developmentally less mature than is the term human neonate, these findings may have implications for development of the premature human neonate.Abbreviations: C-section,cesarean section;GC,glucocorticoid;CBG,corticosteroid-binding globulin

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Correlations between knemometric (lower leg length) growth rates and urine free cortisol excretion, respectively, and serum concentrations of IGF-I, IGF binding protein-3, osteocalcin, carboxy terminal propeptide of type I collagen(PICP), carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen (ICTP), and amino terminal propeptide of type III procollagen(PIIINP) were investigated in 17 asthmatic children aged 7-14 y during treatment with fluticasone propionate, 200 μg, and beclomethasone dipropionate, 400 and 800 μg/d, taken from dry powder inhalers. The study was a double blind, crossover trial with three active treatment periods and two wash-out periods. All periods were 15 d long. Overnight urine free cortisol/creatinine × 106did not correlate with knemometric growth rates or any of the serum markers. Significant correlations (Pearson's correlation coefficient,P) between knemometric growth rates and IGF-I (0.41; 0.006), IGFBP-3 (0.35; 0.02), PICP (0.44; 0.003), ICTP (0.35; 0.001), and PIIINP (0.46; 0.002) were found. Compared with fluticasone propionate, 200 μg, beclomethasone dipropionate, 400 and 800 μg, caused significant suppression of lower leg growth rate (F= 12.41;p= 0.002, andF= 23.30;p= 0.0001, respectively) and of urine free cortisol/creatinine × 106(F= 10.52;p= 0.003, andF= 13.74;p= 0.001). Beclomethasone, 800 μg, caused suppression of PICP compared with fluticasone propionate, 200 μg (F= 8.31;p= 0.008), and beclomethasone, 400 μg (F= 7.53;p= 0.01). Both low (F= 6.82;p= 0.02) and high (F= 23.35;p= 0.0001) doses of beclomethasone were associated with reduced concentrations of ICTP, the high dose being the most suppressive (F= 4.42;p= 0.05). Beclomethasone 400(F= 9.75;p= 0.004) and 800 μg (F= 23.61;p= 0.0001) resulted in reduced levels of PIIINP. Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover.Abbreviations: IGFBP-3,IGF binding protein-3;PICP,carboxy terminal propeptide of type I procollagen;ICTP,carboxy terminal pyridinoline cross-linked telopeptide of type I procollagen;PIIINP,amino terminal propeptide of type III procollagen

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Heat shock proteins (hsps) are produced in the myocardium in response to stresses such as ischemia, hyperthermia, and increased afterload. The role of these stress proteins in the developing myocardium is unknown. Expression of the inducible (hsp 72) and cognate (hsc 73) hsps was determined in the immature ovine myocardium during the perinatal transition, and their role in subsequent myocardial growth was examined. hsp synthesis was also studied during acute afterload stress in newborns by aortic banding to a gradient of 50 torr for 4 h. Expression of the inducible (hsp 72) isoform is developmentally regulated in both right and left ventricles: low levels in the fetus, increasing throughout development, and peaking in the 14-25-d newborn and adult. The cognate (hsc 73) isoform remains unchanged during development in the left ventricle but decreases with age in the right ventricle. The inducible (hsp 72) isoform is also developmentally regulated in the lung, increasing postnatally to a peak in the 14-25-d-old and adult sheep. Finally, newborn myocardium demonstrated a rapid increase in hsp expression in response to afterload stress, similar to that seen in the adult.Abbreviations: hsp,heat shock protein;hsc,cognate form of heat shock protein;ANOVA,analysis of variance;TBS,Tris-buffered saline;TTBS,Tween 20 + TBS

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Left ventricular (LV) output nearly triples at birth, in association with increases in serum catecholamines. Similar increases in catecholaminesin utero, however, do not increase output. We hypothesized that catecholamines increase contractilityin utero, but that output cannot increase until LV loading conditions are changed by oxygen ventilation. To address this hypothesis, we studied nine fetal sheep acutely placed in a warm water bath (40°C). Conductance and manometric catheters were placed in the LV to generate pressure-volume loops during caval occlusion in the nonventilated and oxygen-ventilated states, each under control, dobutamine, and propranolol conditions. Contractility was estimated by the end-systolic pressure-volume relationship, preload by end-diastolic volume, and afterload by arterial elastance. Oxygen ventilation increased LV output 1.4-fold, despite a decrease in contractility to about three-fourths of the nonventilated value. Heart rate remained constant, whereas preload increased and afterload decreased significantly. During oxygen ventilation, dobutamine increased output to 2.3 times the control, nonventilated value, associated with increases in contractility and heart rate and no change in preload and afterload. Although dobutamine increased contractility and heart rate similarly in the nonventilated and oxygen ventilated states, output increased significantly more during ventilation. Similarly, propranolol decreased contractility and heart rate equally in both states, but output decreased far more during ventilation. Thus, oxygen ventilation is associated with advantageous changes in LV load such that the positive inotropic and chronotropic effects of dobutamine are translated into greater increases in LV output.Abbreviations: LV,left ventricle;IVC,inferior vena cava;dP/dtmax,maximum change in pressure per unit time

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

This study investigated developmental changes in the contractile system of the mesenteric small arteries of the rabbit. Arteries about 1 mm in length and 100-250 μm in internal diameter were dissected out from the mesenteric bed of the fetus (29 d of gestation), newborn (3-5 d old), and adult rabbit. Vascular contraction was induced by high KCl concentration, and contractile force was measured using a tension transducer. The sensitivity of vascular contraction to high KCl was similar in the three age groups. To determine the role of Ca influx across the sarcolemma in vascular contraction, the vasorelaxant effect of diltiazem was studied in the artery precontracted with high KCl concentration. The vasorelaxant effect of diltiazem in the fetus and newborn was less than in the adult. To estimate the size of the intracellular Ca pool, caffeine-induced and noradrenaline-induced contraction were measured in the Ca- and Na-free solution. In the fetus and newborn, both the caffeine-induced contraction and noradrenaline-induced contraction were greater than in the adult. The ultrastructural study showed that the endoplasmic reticulum was abundant in the fetus and newborn, and it was scarce in the adult. These data indicate that the dependency of vascular contraction on Ca influx across the sarcolemma increases and the intracellular Ca store decreases with development in the mesenteric resistance arteries.Abbreviations: HEPES,N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid;TES,N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID