摘要:

To determine if developmental variations existed in the second messenger system that mediates cholera toxin (CT) action, the adenylate cyclase (AC) response was studied in 2-wk-old suckling and 6-wk-old weaned rats. AC was assayed in the proximal small intestine 4 h after intraduodenal administration of various doses of CT. Dose-effect analysis showed a 9-fold increase in the sensitivity of the CT-activated cyclase response in suckling rats when measured by the EDso, expressed as ng CT/g body wt (0.03 for 2 wk, 0.27 for 6 wk). When the CT dose was expressed as µ/animal, suckling rats were 50 times more sensitive than 6-wk-old rats. In addition, the CTinduced fluid secretion was closely correlated with the elevated cyclase activities (correlation coefficient: 0.83 for 2 wk, 0.93 for 6 wk). Furthermore, more fluid seemed to be secreted/unit wt of gut in the sucklings, even when the same level of enzyme activity was compared. A maximum of 3- to 4-fold rise in AC activation occurred at 0.5 ng CT/ g body wt, but both the basal and the maximal stimulated levels of AC were not developmentally different. This study demonstrates an in vivo increase in AC responsiveness to CT that may be in part responsible for the increased incidence of toxigenic diarrhea in neonates.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Although the liver plays a central role in glucose homeostasis in the adult, its importance in fetal glucose homeostasis during acute reductions of substrate delivery is unknown. To examine this, we studied eight fetal lambs at 121 ± 2 d gestation. We placed catheters in the descending aorta, inferior vena cava umbilical vein and the left (n = 6) or right (n = 2) hepatic vein, and a balloon occluder around the umbilical cord. At least 4 d after surgery, before and during umbilical cord compression, we measured blood oxygen saturation, glucose, lactate, and Hb concentrations, and blood flows using the radiolabeled microsphere technique. Gluconeogenesis was assessed by infusion of [U14C]lactate. Reducing umbilical flow by 50- 60% from a control value of 181 ± 20 mL/min/kg (mean± SD) caused a dramatic decrease in hepatic blood flow from 332 ± 99 to 94 ± 77 mL/min/100 g (p <0.05). Oxygen delivery to the fetus fell by 50% and that to the liver by 73%. However, hepatic O2 consumption was maintained by increased extraction. Glucose delivery to the liver fell from 67 ± 24 to 20 ± 13 mg/min/100 g (p <0.001), but lactate delivery did not change. In spite of the maintenance of lactate delivery, net hepatic lactate uptake fell significantly from 3.3 ± 1.7 to 1.4 ± 0.9 mg/minlOO g (p <0.05). This could account, in part, for the increase of blood lactate concentration from 16 ± 4 to 27 ± 7 mg/dl. Although hepatic glucose delivery fell markedly, net glucose production by the liver increased from 0.1 ± 2.4 to 3.9 ± 7.3 mg/ min/100 g (p <0.05). Presumably, this glucose production is from glycogenolysis because no hepatic gluconeogenesis from labeled lactate could be detected. During umbilical cord compression, hepatic glycogenolysis contributed 1.5 ± 2.8 mg/min/kg (30%) of total glucose utilized by the fetus. The mechanisms responsible for fetal hepatic glycogenolysis are yet to be delineated.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

β-glucuronidase hydrolyzes glucuronic acid from bilirubin glucuronides. The unconjugated bilirubin that results is more readily absorbed from the intestine. Human breast milk has significantβ-glucuronidase activity, and it has been suggested that the milk may play an etiologic role in the hyperbilirubinemia commonly seen in breast-fed infants. To test whether breast-milk can facilitate intestinal bilirubin absorption, pairs of rats were fitted with bile duct and duodenal catheters. One rat of each pair received an intraduodenal infusion of rat bile plus breast-milk; the other rat received a similar amount of bile and milk plus the,β-glucuronidase inhibitor saccharolactone. Rats receiving saccharolactone excreted significantly less bilirubin in their bile, suggesting that inhibition ofβ-glucuronidase decreased intestinal absorption of bilirubin. These findings were not seen in similar experiments when saline was substituted for human breast-milk.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To determine whether the initiation of fetal lung surfactant phospholipid production and the activation of the gene for the 35-kD surfactant-associated protein are dependent on circulating corticosteroids, we cultured dexamethasone- responsive explants of 15- to 17-d fetal rat lung in medium with 1 % FCS (controls), charcoal-stripped 1% FCS, or a variety of glucocorticoid antagonists. The steroid antagonist RU 486 almost completely abolished specific cytoplasmic and nuclear dexamethasone binding in the explants but had no glucocorticoid-agonist activity. There was a significant increase in disaturated phosphatidylcholine synthesis during 7 d in culture in control explants (78%) and in those cultured with Charcoal-stripped serum (83%), RU 486 (82%), or the other glucocorticoid antagonists—clotrimazole, cortexelone, and 11-ketoprogesterone. Specific mRNA for surfactant-associated protein A was not detectable in preculture 17-d lung tissue, but accumulated to the same extent in cultures with or without RU 486 in the medium. These findings support the view that expression of the genes responsible for the synthesis of the various components of surfactant is not induced by glucocorticoids, but by signals contained within the lung tissue itself. The role of circulating hormones is later acceleration and modulation of surfactant production.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We determined whether closing the ductus arteriosus of the fetal lamb several d before birth would cause persistent pulmonary hypertension after birth. Six experimental fetuses who had their ductus arteriosus ligated 3–17 d before delivery, three control fetuses who had sham ligation of the ductus arteriosus 14 d before delivery, and six control fetuses who had no prenatal surgery were delivered by cesarean section between 138 and 144 d of gestation. Each was instrumented to measure pulmonary and systemic arterial pressures and pulmonary blood flow. Each newborn lamb was ventilated with room air during the first 45 min after birth and then with decreasing amounts of inspired oxygen from 100 to 9%. Pulmonary arterial pressure decreased significantly when ventilation was begun in the control lambs but not in the lambs who had their ductus arteriosus ligated before delivery. Throughout the experiment, pulmonary arterial pressure and total pulmonary resistance were significantly higher, and pulmonary blood flow was significantly lower in the lambs who had their ductus arteriosus ligated before delivery. In two of them, pulmonary arterial pressure was greater than or equal to systemic arterial pressure, even during ventilation with 100% oxygen. This animal preparation provides a method of investigating persistent pulmonary hypertension in the newborn lamb and may provide insight into an etiology of the syndrome of persistent pulmonary hypertension of the newborn.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The clinical syndrome of persistent pulmonary hypertension of the newborn includes a developmentally abnormal pulmonary microvasculature which contains excessive amounts of muscle and which cannot adapt to air breathing in the perinatal period. Surgical ligation of the ductus arteriosus of the fetal lamb has produced a physiologic model of pulmonary hypertension of the newborn. The aim of the present investigation is to determine whether surgical ligation of the ductus arteriosus in fetal sheep produces anatomic changes in the pulmonary blood vessels. The pulmonary vasculature of seven neonatal lambs that underwent surgical ligation of the ductus arteriosus from 6 to 17 d before birth was compared to that of five control lambs with a patent ductus arteriosus without fetal surgery and three control lambs with a patent ductus arteriosus that underwent sham surgery. Quantitative microscopic analysis of the barium gelatin-filled peripheral pulmonary vascular bed revealed an increase in the proportion of partially and fully muscularized pulmonary arteries at the level of the terminal bronchiole and within the acinus (p<0.0001). This finding demonstrates that medial muscle develops in areas of the distal pulmonary vascular bed where it is normally absent. Periadventitial fibrosis surrounding intraacinar pulmonary arteries was also present. No change in the number of small intraacinar arteries was detected. This structural remodeling of the peripheral pulmonary vascular bed was initiated in utero by ductus arteriosus occlusion. Prenatal closure of the ductus arteriosus for 6 to 17 d in fetal lambs produces anatomic changes in small pulmonary arteries of the newborn lamb. These anatomic changes are similar to pathologic alterations reported in human neonates dying with idiopathic persistent pulmonary hypertension of the newborn.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Periodic breathing cycle duration (PCD), the time interval from the beginning of one respiratory pause to the beginning of the next pause within an episode of periodic breathing (PB), was measured by examination of 24-h impedance pneumograms in 51 preterm infants. Calculations of the SD of PCD within a given PB episode (~3 s) and comparison of PCD values between two PB episodes in each infant (r=0.68) revealed considerable variability in PCD. This variability was not related to the number of cycles in the PB episode or to the amount of PB in the recording. Contrary to the decrease in PCD from 15.0 s at 1 wk to 12.4 s at 12 wk in term infants reported previously, PCD did not vary as a function of postconceptional, gestational, or postnatal age in our preterm population. PCD has limited value as an indicator of chemoreceptor maturation in the preterm infant, and most likely reflects transient adjustments in respiratory system control.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Low blood ionized calcium levels have been reported previously in association with alkalosis in infants undergoing hyperventilation for persistent pulmonary hypertension. We investigated the effect of acute calcium infusions on the cardiopulmonary status of 10 hypocalcemic, hyperventilated infants with persistent pulmonary hypertension. Acid-base status, arterial partial pressure of oxygen, vital signs, and echocardiographically determined right and left systolic time interval ratios and left ventricular shortening fractions were obtained before and after rapid infusions of calcium gluconate or saline. At 5 and 15 min after calcium infusion, but not after saline infusion, there were significant decreases in both right and left ventricular systolic time interval ratios, and an increase in transcutaneous PO2and PaO2that coincided with peak levels of ionized calcium. These findings provide evidence that high levels of ionized calcium in newborns with persistent pulmonary hypertension transiently improve myocardial performance and oxygenation.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Human colostrum manifests antioxidant properties, being capable of spontaneous reduction of cytochrome c, depletion of polymorphonuclear leukocyteproduced H2O2 and protection of epithelial cells from PMN-mediated detachment. These activities can be electrophoretically concentrated at either 3.5 kD or 50 kD dialysis membranes at mildly alkaline pH. They are progressively lost under increasingly alkaline conditions. They are resistant to 1-mM /V-ethylmaleimide. Examination of a series of antioxidant compounds showed that ascorbate manifests several characteristics of colostrum, being able to reduce cytochrome c and deplete H2O2, but not altering PMN-mediated HEp2 cell detachment. Addition of ascorbate oxidase to colostrum decreased its cytochrome creducing activity by more than 85%, decreased its H2O2- depleting activity by nearly 50%, but did not alter its ability to protect HEp2 cells, all suggesting heterogeneity of colostral antioxidant activities. Treatment of colostrum with an enzymatic system (xanthine + xanthine oxidase) known to destroy ascorbate's cytochrome c-reducing activity yielded paradoxical results, decreasing colostral cytochrome c reduction in a dose-related manner, while increasing its H2O2-depleting activity. These studies demonstrate that a colostral component similar to ascorbate, a known antioxidant compound is responsible for the majority of colostral cytochrome c-reducing activity, for about half of its H2O2-depleting activity, and little, if any, of its protective effect on HEp2 cells. Thus, colostral antioxidant activity is heterogeneous.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Minute ventilation, arterial blood gases and pH, cardiac output, and transdiaphragmatic force generation were measured in eight anesthetized, tracheostomized piglets before and after administration of 40 µg/kg body wt of digoxin. No changes were noted in cardiac output, heart rate, tidal vol, respiratory rate, or minute ventilation. Blood pressure decreased from baseline to 60 min postinfusion. No change was noted in the force frequency curves at 30 and 60 min postinfusion. Serum digoxin levels averaged 10.4 ng/mL at 30 min and 5.6 ng/mL at 60 min. In seven control animals, no changes were noted in any ventilatory or hemodynamic parameter from baseline to 60 min. In contrast to the reported effects of digoxin on the diaphragm of adult humans and animals, digoxin did not augment diaphragmatic contractility in normal infant swine.

ISSN:0031-3998    

出版商:OVID    

年代:1989

数据来源: OVID