Intestinal uptake and transmission of macromolecules into the blood in the young guinea pig.

The developmental changes in the ability of the small intestinal epithelium to take up and transfer into blood the macromolecules bovine serum albumin (BSA), bovine immunoglobulin G (BIgG), and fluorescein isothiocyanate-labeled dextran 70,000 (FITC-dextran) were studied in guinea pigs 0-14 days of age. In addition, in the same animals, the activities of the proteases cathepsin B and D within the intestinal mucosa were measured. Four hours after gavage feeding, 0-day-old guinea pigs showed an uptake of the markers into the enterocytes throughout the small intestine. In 2-day-old guinea pigs, the markers were only detected in the enterocytes in the distal part. All three macromolecules passed into the blood in these young animals. In 7-day-old guinea pigs, no epithelial marker uptake was observed, but low levels of BSA and FITC-dextran could still be detected in serum. Neither epithelial uptake nor transfer of the markers to the blood could be found in the animals that were 14 days of age. The activity of cathepsin B and D in the intestinal mucosa showed a tendency to increase with age, and for all ages the activity in the distal part was higher than in the proximal part. The results showed that the small intestine in guinea pigs at birth is capable of macromolecular uptake and transfer into the circulation. This ability decreased with age eventually leading to intestinal closure after 1 week. The histological findings implied that intestinal closure was a consequence of a replacement of fetal absorptive cells with adult cells lacking this ability.     

Relationship of birth weight to the pathogenesis of necrotizing enterocolitis in the neonatal piglet

The relationship between birth weight and the development of necrotizing enterocolitis (NEC) was studied in the term-delivered neonatal piglet. Hypoxia (pO2 less than 30% for 1 h) coupled with hyperviscosity (hematocrit more than 75%), with and without splenectomy, resulted in a high frequency and severity of NEC. This effect was most pronounced in low birth weight (LBW) animals. A statistically significant inverse relationship was found between birth weight and the number and severity of lesions. Splenectomy increased the incidence and severity of lesions particularly in LBW animals. A predominance of lesions was found in the distal ileum with occasional occurrences elsewhere in the small bowel and in the proximal colon. The neonatal piglet is capable of producing the full spectrum of NEC under acceptable experimental conditions. LBW is a significant predisposing factor in the pathogenesis of NEC.     

Studies on the kinetics and renal excretion of low and high molecular weight dextrans in preterm babies,newborns and young infants

Administration of low and high molecular weight dextrans in the initial phase of shock is no longer controversial. The special conditions in newborns, however, have been insufficiently considered in planning therapy. This investigation aimed at determining the biological half-lives of dextran 40 (Rheomacrodex^®) and dextran 60 (Macrodex^®) in this age group. The half-life of dextran 40 was found to be 60 min and that of dextran 60 3 h. Preterm babies and newborns excrete up to 25% less dextran 40 and 60 in 24 h than infants and adults. Normal adult values for excretion are only reached towards the end of the first year of life.     

Body composition and cold resistance of the neonatal pig from European (Large White) and Chinese (Meishan) breeds

Body composition, plasma parameters and cold resistance were compared in neonatal pigs from Chinese (Meishan, Ms) and European (Large White, Lw) breeds. Newborn Ms pigs weighed less but had a higher (p less than 0.05) percentage of body dry matter and protein than the Lw pigs, whereas both breeds had similar levels of body fat and liver and muscle glycogen. Plasma concentrations of fructose and alpha-fetoprotein were lower (p less than 0.05) in the newborn Ms pigs. Cold resistance test performed in a 6-7 degrees C environment on the same piglets when aged 2 and 24 h, showed that in both breeds, cold resistance was closely dependent upon body weight and significantly improved (p less than 0.01) with age. Despite their 16% lower body weight, Ms piglets were, at both ages studied, as resistant to cold as the Lw ones. Breed had no effect on pretest concentration of plasma glucose and noradrenaline, but pretest concentrations of plasma free fatty acids (FFA) were higher (p less than 0.01) in the Ms than in Lw piglets and those of adrenaline were lower (p less than 0.01) in the Ms Lw piglets and those of adrenaline were lower (p less than 0.01) in the Ms piglets. Breed had no significant effect on the response of plasma glucose, FFA and catecholamines during exposure to cold. At both ages of exposure, plasma concentrations of glucose and catecholamines were significantly increased. Plasma concentrations of FFA were increased (p less than 0.01) at 2 h, but at 24 h a decrease (p less than 0.01) was observed during cold exposure. Colostrum from Ms sows had greater concentration of lipids than that from Lw sows. It is suggested that the similar resistance to cold of the Ms and Lw piglets despite the lower body weight of the former is due, in part, to a greater availability of FFA as an energy source.     

Prematurity and perinatal mortality in the Rhesus (Macaca mulatta): relationship to birth weight and gestational age.

While the relative influence of birth weight and gestational age in determining perinatal mortality has not been definitively established, it has been assumed that birth weight makes the predominant contribution to perinatal mortality. The joint effects of birth weight and gestational age were examined by analyzing approximately 2,500 births from timed pregnancies in two rhesus (Macaca mulatta) breeding colonies. Perinatal events in the rhesus are described and shown to be similar to the human. The results demonstrate that gestational age is as important as birth weight in determining perinatal mortality. Since the degree of accuracy in the estimation of rhesus gestational age was much greater than is usually attained in human studies, the estimation of gestational age from the last menses may be too crude to determine the importance of this variable in human perinatal mortality.     

Acetylcholine-induced coronary vasoconstriction and negative inotropy in the neonatal pig heart.

We investigated the influence of exogenously administered acetylcholine, nitric oxide, ADP, ATP, bradykinin, and substance P on coronary vascular tone in isolated, neonatal pig hearts (less than or equal to 4 d). Paced (180 bpm), isovolumically beating hearts underwent retrograde aortic perfusion, with an erythrocyte-enriched solution (hematocrit 0.15-0.20) at constant coronary flow (approximately 2.5 mL/min/g) corresponding to a perfusion pressure of approximately 60 mm Hg. Agonists were injected into the aortic root, and the peak change in coronary perfusion pressure from baseline and left ventricular pressure development were assessed. Nitric oxide (3 microL), ADP (30 nmol), ATP (30 nmol), bradykinin (125 ng), and substance P (50 ng) decreased the perfusion pressure (vasodilation) by 16.9 +/- 1.2, 25.3 +/- 4.4, 18.3 +/- 1.2, 18.9 +/- 1.4, and 7.1 +/- 1.6 mm Hg, respectively. Acetylcholine (0.5 and 1.0 nmol) produced a modest decrease in perfusion pressure (vasodilatation) of 4.2 +/- 0.8 and 3.8 +/- 0.5 mm Hg, respectively, whereas acetylcholine (5, 20, and 100 nmol) increased the perfusion pressure (vasoconstriction) by 16.7 +/- 2.7, 48.2 +/- 8.2, and 85.3 +/- 15.1 mm Hg, respectively. Acetylcholine also decreased left ventricular peak systolic pressure from 108.7 +/- 5.0 to 69.2 +/- 4.6, 56.3 +/- 6.1, and 48.2 +/- 6.4 mm Hg, for the 5, 20, and 100 nmol doses, respectively. Responses to acetylcholine were abolished by atropine (50 nmol). In a separate group of hearts, indomethacin (10(-6) M) reduced the peak change in perfusion pressure for the 5, 20, and 100 nmol doses of acetylcholine by 87%, 66%, and 48%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of morphine and naloxone on endothelin and its receptors in newborn piglet brain vascular endothelial cells: clinical implications in neonatal care

The present study examines the hypothesis that morphine exposure alters newborn brain vascular endothelial cell production of endothelin (ET)-1, as well as the mRNA expression of its receptors. Newborn piglet vascular endothelial cells were treated with morphine (100 ng/mL media), naloxone (100 ng/mL media), or drug-free media (control) for 6, 24, 48, and 96 h. Media was analyzed for ET-1 and big ET-1 levels and the cells were assessed for ETA and ETB receptor mRNA expression. Morphine exposure progressively increased ET-1 production from 6 to 96 h with concurrent reductions in big ET-1 levels starting at 24 h to almost undetectable levels by 96 h. Whereas ETA receptor mRNA expression increased 2-fold at 6 h and 4-fold at 96 h, ETB receptor mRNA expression remained unchanged. Naloxone exposure caused significant decreases in ET-1 levels, whereas an opposite effect was noted in big ET-1 levels, which increased from 6 through 96 h. Naloxone caused a progressive decrease in ETA receptor mRNA expression at 6 h through 96 h and a 2-fold increase in ETB receptor mRNA expression at 48 and 96 h. Increased ET-1 and its receptors in response to morphine may suggest altered cerebrovascular perfusion and brain metabolism in the immature piglet brain.     

The binding of 125I-TSH to thyroid cell receptors previously deformed (in neonatal age) by gonadotropin treatment.

Single gonadotropin treatment of newborn rats caused a 63-71% decrease of TSH-binding on isolated thyroid cells prepared from thyroid glands of both 6- and 13-month-old animals. This fact points out that: (1) in newborn animals the hormone receptors are still plastic and deformable and (2) the damaging effect of the analogous hormone manifests itself at the receptor level.     

Birth weight and hospital admission before the age of 2 years.

Admission rates to hospital of children born weighing 1500 g or less were compared with those born with birth weights over 1500 g in a retrospective analysis of routinely collected data from the Oxford Record Linkage Study. The children were born in the three five year periods 1968-72, 1974-8, and 1979-83 to women resident in Oxfordshire and West Berkshire. The main measures of the study were survival rates to 28 days after birth and hospital admissions of survivors up to the age of two years. Among babies weighing 1500 g or less, neonatal survival rates rose from 350.2 per 1000 total births in 1968-72 to 577.4 per 1000 among births in 1979-83. Over the same period, the proportion of children admitted to hospital at least once before the age of 2 years rose from 218.6 per 1000 survivors to 444.4 per 1000. In the children with birth weights over 1500 g, survival rates rose from 985.5 to 995.9 per 1000 births and hospital admission rates rose from 98.2 to 144.4 per 1000 survivors over the same time period. Although very low birthweight children did not contribute significantly to total hospital bed occupancy, because their numbers were small in relation to the total number of children in the population, their contribution increased between the five year periods 1968-72 and 1979-83. It should therefore be continuously monitored using routine systems.