摘要:

To determine the effects of early antigen exposure on the maturation of the gastrointestinal mucosal barrier, rat pups were divided into three groups at the age of 14 d. In addition to normal maternal milk, group CM (n= 24) received daily a gavage feed of cow's milk and group PH (n= 20) a whey protein hydrolysate during the experimental feeding period (14–20 d). Controls (n= 15) remained on maternal milk only. At 21 d, when “gut closure” normally occurs, intestinal absorption of horseradish peroxidase (HRP), was examinedin vitroin Ussing chambers. The absorption of intact HRP [geometric mean (95% confidence interval)] was significantly higher in group CM [35.3 (16.7, 74.7) ng.h−1.cm−2] than in group PH [5.2 (1.4, 19.5) ng.h−1cm−2] and in controls [3.4 (0.8, 15.1) ng.h−1. cm−2;F= 5.54,p= 0.006]. The absorption of degraded HRP was comparable in all groups. There were no modifications in electrical parameters in association with increased mucosal permeability to HRP. Furthermore, in group CM electron-microscopic studies disclosed accumulation of HRP in the cytoplasm of the epithelial cells and in the intercellular spaces where cell junctions remained unaltered. These results indicate that early administration of antigens delays the process of gut closure. They further suggest that continuously enhanced endocytosis of macro-molecules is induced by an insult to the mucosa as part of the host response to these antigens, irrespective of the protection afforded by maternal milk. (Pediatr Res 32: 301–305, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The synergistic effects of dexamethasone (DEX) and thyroxine (T4) on the postnatal maturation of the 13-d-old rodent small intestine has been studied. Previous studies have shown that hydrocortisone and T4produced a synergistic response in enzyme maturation. However, T4elevates corticosteroid-binding globulin, which reduces the clearance of hydrocortisone. Thus, the apparent synergy between T4and hydrocortisone may have been due to increased glucocorticoid availability. DEX, which does not bind to corticosteroid-binding globulin, was given (d 8–12) at 25 pmol (i.e. 0.01 μg)/g body wt/d as established by a dose-response study in which this dose of DEX induced one third the maximum response in sucrase activity. In this way, synergy with T4(130 pmol/g body wt/d, i.e. 0.1 μg/g body wt/d, d 5–12) could still be observed. Glucoamylase, lactase, acid β-galactosidase, alkaline phosphatase, and sucrase activities were determined in two regions of the small intestine. Overall, the results for the two hormones administered alone showed intestinal maturation to be not significantly affected in the T4group and partially stimulated in the DEX group. When combined, DEX + T4synergistically increased jejunal sucrase, ileal glucoamylase, and duodenal alkaline phosphatase, and lowered ileal acid β-galactosidase. The striking exceptions to the general pattern were two brush border enzymes that normally decline during intestinal maturation, namely ileal alkaline phosphatase and jejunal and ileal lactase. For these enzymes, DEX alone did not elicit precocious maturation, and there was no evidence for a synergistic interaction of these two hormones. Serum corticosterone concentrations also were measured. When corticosterone concentrations were compared with enzyme activity, no correlation was found. Thus, DEX + T4act synergistically in the maturation of four enzymes in the rodent small intestine. Lactase and ileal alkaline phosphatase are regulated differently. Further studies are required to determine the mechanism through which T4enhances the DEX effect. (Pediatr Res 32: 306–311, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

L-Carnitine plays a crucial role in the perinatal transition from carbohydrate to lipid-derived energy. To examine the potential contribution of assimilated dietary carnitine to the elevated hepatic concentrations in newborns, we measured carnitine concentrations in sow milk, jejunum, and liver, andin vitrojejunal carnitine transport in piglets aged 1–36 d. Hepatic and sow milk total carnitine concentrations peaked soon after birth and declined with age (p= 0.035 and 0.026, respectively). Although jejunal total carnitine concentrations remained stable, jejunal carnitine flux was higher at 2 d of age than in older piglets. To examine the possible signals that regulate hepatic carnitine, portal enteroinsular hormones were measured by RIA. Portal glucagon (p= 0.0006), insulin (p= 0.0001), and glucagon:insulin ratio (p= 0.037) were related to age. Portal glucagon was highest in newborns and during weaning, whereas insulin increased progressively with age; the portal glucagon:insulin ratio, like hepatic carnitine, peaked soon after birth and fell with age. A multiple regression analysis indicated a positive association between glucagon and hepatic carnitine and a negative one between insulin and hepatic carnitine (R= 0.802,p= 0.001). An overall pattern of elevated dietary carnitine levels and increased small intestinal absorption and hepatic accumulation of carnitine is noted in early development. The finding of a similar pattern in glucagon-to-insulin ratio suggests that both hormones may participate in the regulation of enterohepatic carnitine distribution in newborns. (Pediatr Res 32: 312–316, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Carrier-mediated β-D-hydroxybutyrate transport in brush-border membrane (maternal-sided) vesicles prepared from trophoblast rat placenta was studied. The existence of a carrier-mediated transport system for β-D-hydroxybutyrate in brush-border membrane vesicles was substantiated by the strong inhibitory effect of the protein modifier p-chloromercuriphenyl sulfonic acid and by the saturability of β-D-hydroxybutyrate uptake as a function of β-D-hydroxybutyrate concentration. β-D-hydroxybutyrate uptake was stimulated by the presence of an inward-directed proton gradient but not by an inward-directed Na+gradient. The mechanism for transport of β-D-hydroxybutyrate seems to be a β-D-hydroxybutyrate/H+symport and not a β-D-hydroxybutyrate/OH−antiport because β-D-hydroxybutyrate transport was not sensitive to 4,4-diisothiocyano-2,2‘-stilbenedisulfonic acid or furosemide. The Km, Vmax, and kdcalculated by applying the iteration procedure to the data were 16 mM, 58 nmol. mg−1.10 s−1, and 0 nL.mg−1-s−1, respectively. The β-D-hydroxybutyrate transport system might be shared by other monocarboxylic acids, and the carrier shows reversibility and exchange properties. There were no significant changes in the kinetic parameters of the β-D-hydroxybutyrate transport system during the last 3 d of gestation. Nevertheless, there was a significant increase in the capacity of the β-D-hydroxybutyrate transport system in brush-border membrane vesicles prepared from fasted pregnant rats, suggesting that the rise in maternal ketone body levels occurring as a consequence of maternal starvation is concurrent with the stimulation of the activity of the β-D-hydroxybutyrate placental carrier to supply the fetus with ketone bodies. The signal mediating the stimulation of carrier activity due to starvation remains to be elucidated.(Pediatr Res32: 317–323, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The ability of synthetic metalloporphyrins to suppress heme oxygenase activity and bilirubin formation has recently become of considerable clinical and experimental interest for suppression of jaundice in humans, including neonatal hyperbilirubinemia. The present investigation compares the biochemical effects of Sn- and Znprotoporphyrins on the predominant heme oxygenase iso-zyme present in the brain (HO-2) at activity, protein, and transcript levels and describes the ability of Sn-protopor-phyrin to adversely affect this isozyme. Specifically, 6 h after a modest dose (50 μmol/kg, i.v.) of Sn-protoporphyrin, heme oxygenase activity in rat brain was nearly undetectable. In addition, as revealed by Western blot analysis, HO-2 protein level was decreased by 20% and the electrophoretic behavior of the protein in the microsomal membranes was altered. Moreover, the activity of NADPH-cytochrome P-450 reductase, which is required for the oxidation of heme molecule, was markedly decreased (60% of control). Western immunoblot analysis revealed also a pronounced decrease in the reductase protein level. The inducible form of heme oxygenase, HO-1, was not detectable by immunoblotting in brain microsomes of either control or Sn-protoporphyrin-treated animals. Northern blot analyses did not reveal decreases in the levels of the single HO-1 mRNA (1.8 kb) or the two HO-2 transcripts (1.3 and 1.9 kb), suggesting that Sn-protoporphyrin mediates its effects on heme oxygenase isozymes at the protein level. Zn-protoporphyrin, on the other hand, had no deleterious effect on brain parameters presently investigated. The data suggest that Sn-protoporphyrin exerts its inhibitory effects on heme oxygenase activity in the brain through multiple mechanisms involving direct effect on HO-2 protein and its cellular level, inhibiting NADPH-cytochrome P-450 reductase activity, decreasing the cellular content of the reductase, as well as inhibiting heme oxygenase activity by serving as a competitive inhibitor. We suggest that Zn-protoporphyrin may be the safer alternative if metalloporphyrins are to be used to control hyperbilirubinemia. (Pediatr Res 32: 324–329, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The purpose of the present study is to show that dietary caffeine, heart tissue Zn levels, and metallothionein (MT) concentration are all interrelated in newborn rats. Dams with eight pups in the control group were fed a 20% protein diet upon delivery, whereas dams in the experimental group were fed a 20% protein diet supplemented with caffeine (2 mg/100 g body weight). Offspring were killed at d 22 postbirth and the hearts and livers were removed to determine the Zn and MT concentrations. Hearts of the newborn rats in the caffeine group showed decreased Zn levels as well as decreased MT concentration. To explain the observed effects in newborn rats, the relationship between Zn and MT levels was studied in adult female rats. They were injected intraperitoneally with either ZnCl2(20 mg/kg body weight) dissolved in saline solution or ZnCl2and caffeine (4 mg/kg body weight) over a period of 2 d. Injection of ZnCl2into adult female rats resulted in an increase in heart MT levels, whereas injection of caffeine caused decreased Zn levels and MT concentration. Current findings indicate that dietary caffeine intake during the lactational period by newborn pups causes a decrease of the heart Zn and MT levels. (Pediatr Res 32: 330–332, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Although atrial morphologic changes are well documented, the description of early atrial function is limited. We used videomicroscopic methods to define the function of the contracting atrium in stage 16 to 24 white Leghorn chick embryos. We exposed the embryo in ovo (right side up) and imaged the ventricle, then repositioned the embryo (left side up) and imaged the atrium (n≥ 8 per stage). We traced the atrial endocardial border and then measured atrial perimeter (mm) and cross-sectional area (mm2). A 20-MHz pulsed Doppler velocity meter was used to measure atrioventricular blood velocity during atrial imaging in an additional six stage 21 embryos. Data were tested by analysis of variance and regression analysis. Mean heart rate change after repositioning was −4 ± 1%. Atrial maximum and minimum area increased linearly versus embryo stage (y= 0.10x− 1.41,r= 0.89,p< 0.05 and y = 0.05x− 0.67,r= 0.82,p< 0.05, respectively). Shortening fraction (percentage of reduction) of atrial perimeter and area decreased from 32.3 ± 2.0% to 27.5 ± 1.8% (p< 0.05) and 56.2 ± 3.0% to 47.7 ± 2.0% (p< 0.05), respectively, from stage 16 to 24. During atrial contraction, the velocity of circumferential wall shortening increased linearly with stage (y= 0.22x− 2.08,r= 0.81,p< 0.01); however, the velocity of lengthening was similar between stages (p= 0.45). Simultaneous atrial imaging and pulsed Doppler velocity measurement showed that passive atrioventricular flow occurred late in atrial lengthening and active atrioventricular flow occurred during atrial contraction. Thus, atrial function increases in parallel with morphogenesis during early cardiac development, and measures of atrial function can now be incorporated into a physiologic model of the developing cardiovascular system. (Pediatr Res 32: 333–337, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Ultrasonic visualization of the human fetal subdiaphragmatic area demonstrated anatomical relationships, different from descriptions in the literature. Four human fetal postmortem specimens at 18, 26, 28, and 34 wk of gestation were examined to ascertain morphologic details of intra- and perihepatic vasculature. Drawings of these dissected preparations were compared with ultrasonic images from the same region. With both methods the presence of a venous vestibulum immediately proximate to the diaphragm could be demonstrated. The abdominal inferior vena cava ends in a funnel-like structure, which also contains the orifices of the hepatic veins, the ductus venosus, and a phrenic vein. A considerable variability in Doppler flow recordings could result from blood propelling out of these various vessels into the vestibulum. It is, therefore, suggested that information on blood-flow velocities in venous hepatic vessels should be obtained more distally in the separate vessels and not at the entrance into the right atrium. (Pediatr Res 32: 338–341, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Mechanisms for the control of episodic fetal breathing movements or the onset of continuous breathing at birth remain unknown. Lung distension with 100% O2at a continuous positive airway pressure of 30 cm H2O may induce arousal and continuous breathing. To investigate1) the threshold range of arterial oxygen tension (PaO2) for the onset of arousal and breathing and2) the graded response of breathing to various levels of PaO2, we studied 10 fetal sheep between 135 and 142 d of gestation (term = 147 ± 2 d). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, arterial pH, and blood gas tensions. PaO2threshold was determined through an indwelling O2sensor catheter. Fetal lungs were distended at a continuous positive airway pressure of 40 cm H2O with 100%. N2or with O2ranging from 40 to 100% via an in situ endotracheal tube. At the onset of arousal (n= 10), PaO2, arterial carbon dioxide tension, and Hb O2saturation increased from control values of 21.7 ± 0.75 torr (2.9 ± 0.09 kPa), 41.8 ± 1.1 torr (5.47 ± 0.15 kPa), and 52.9 ± 2.6% to 65.6 ± 9.6 torr (8.74 ± 1.28 kPa), 46.9 ±1.3 torr (6.25 ± 0.17 kPa), and 92.9 ± 2.06%, respectively, whereas the pH decreased from 7.31 ± 0.006 to 7.27 ± 0.009 (mean ± SEM; p = 0.001, 0.04, 0.002, and 0.001, respectively). Seven of 10 fetuses breathed continuously. In these fetuses, PaO2and arterial carbon dioxide tension further increased and pH decreased; however, no further significant increase in Hb O2saturation was observed. Breathing stopped at a PaO2of 38.5 ± 9.5 torr (5.1 ±1.3 kPa) but could be restarted by increasing the PaO2. In response to an increase in fetal PaO2(30–60 torr; 4–8 kPa), amplitude of breathing and total respiratory output significantly increased from the control values. Further increases in PaO2or Hb O2saturation did not significantly affect the respiratory output. Hb O2saturation and arterial pH had the most confounding effects on frequency and amplitude of breathing, respectively. Among the various sleep states, arousal had the most profound effects on respiratory output. We conclude that 1) very high levels of PaO2are not necessary to initiate arousal and continuous breathing and2) further increments in Hb O2saturation above the threshold level have no significant effect on breathing responses. (Pediatr Res 32: 342–349, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID