bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal Development of Plasma-Lipid-Clearing Enzymes (Lipoprotein Lipase, Hepatic Lipase and Lecithin:Cholesterol Acyl Transferase) and Lipid Profiles in Suckling Rats
Authors: Mao Jeein , Hamosh Margit
Published: October 2009

We examined the activity of plasma circulating lipoprotein lipase and hepatic lipase, lecithimcholesterol acyl transferase (LCAT), as well as lipid profiles in Sprague-Dawley rats from 1 day until 29 days of age. Plasma lipoprotein lipase activity peaked between ages 5 and 15 days and decreased after weaning, while plasma hepatic lipase activity remained constantly low during the suckling period and increased after weaning. No statistically significant difference in LCAT activity was seen from birth until weaning. Plasma triglycerides, as well as free fatty acids, decreased significantly after birth. Total plasma cholesterol increased during the suckling period and decreased after weaning. HDL cholesterol increased after the first 10 days of life, and free cholesterol remained constant after an initial decrease from birth to the 5th day of life. In conclusion, the enzymes asociated with the metabolism of triglycerides, cholesterols and phospholipids are well developed in the rat shortly after birth.
Bubbles and Computer-Aided Image Analysis for Evaluation of Surfactant Inhibition
Authors: Berggren Per , Eklind Jonas , Linderholm Bim , Robertson Bengt
Published: October 2009

Surfactant (Curosurf, diluted to 5 mg/ml) was suspended in normal saline with 3 mM CaCl2 and mixed with different concentrations of albumin or fibrinogen. The samples were vortexed to generate microbubbles, and the equivalent circle diameter of these bubbles was determined with computer-aided image analysis. Bubbles in the original surfactant suspension had an average diameter of 27 μm after 2 min, and their size increased only little during a 15-min period of observation. The diameter of bubbles generated in the presence of albumin (4 or 40 mg/ml) or fibrinogen (4 mg/ml) was 4–5 times larger, indicating surfactant inhibition. We conclude that evaluation of microbubble stability with image analysis provides an objective and rapid assessment of surfactant inhibition, and we speculate that the method could also be used for quantification of surfactant activity in airway samples.
Surfactant Administration and the Cerebral Circulation
Authors: Skov Liselotte , Bell Angela , Greisen Gorm
Published: October 2009

We have used two main techniques to investigate the effect of surfactant therapy on the cerebral circulation in 34 babies. Twenty-one babies were studied using near infrared spectroscopy and 13 had cerebral blood flow measured using a xenon clearance technique. Other measures recorded included amplitude integrated EEG, mean arterial blood pressure and central venous or oesophageal pressure. There was a marked depression in EEG activity lasting for 10–20 min after surfactant administration. Cerebral blood volume and cerebral blood flow were maintained in most infants in spite of a fall in mean arterial blood pressure. We conclude that factors other than cerebral ischaemia cause the transient disturbance in electrophysiologic activity.
Surfactant Replacement Therapy and the Prevalence of Acute Retinopathy of Prematurity
Authors: Tubman Richard J. , Rankin Simon J. , Halliday Henry L. , Johnston Stewart S.
Published: October 2009

To determine if surfactant replacement treatment is associated with an increase in the prevalence of retinopathy of prematurity (ROP) we studied 76 preterm babies who were treated with porcine surfactant (Curosurf) for severe respiratory distress syndrome from 1985 to 1990. Babies were first examined by indirect ophthalmoscopy at the equivalent of 32 weeks post-menstrual age and subsequently at 2-week intervals until discharge from hospital. Findings were documented according to the International Classification of ROP. Sixty-two (82%) babies survived to discharge, 7 survivors were not examined due to transfer elsewhere. Acute ROP developed in 14 (29%) of the 49 babies examined (7 stage I, 4 stage II, 2 stage III, and 1 stage IV); one baby required cryotherapy. No baby of birthweight > 1,500 g developed ROP. The prevalence of ROP was similar to that reported for non-surfactant-treated very-low-birthweight babies. We conclude that Curosurf treatment does not increase the risk of acute ROP in surviving very-low-birthweight babies.
Gastric Secretion in Infants
Authors: Mouterde Olivier , Dacher Jean-Nicolas , Basuyau Jean-Paul , Mallet Eric
Published: October 2009

Sudden infant death is a problem of paediatric public health which remains an unpredictable phenomenon of unknown aetiology. Many authors have discussed the role of a neurovegetative aetiology, the role of the vagus nerve being suspected above all. A biological approach to vagal tone was attempted by assaying intragastric pepsin and serum pepsinogen and calculating the ratio of pepsin to acid in control infants, and by assaying serum pepsinogen levels in infants having suffered an apparently life-threatening event (ALTE) or who died of the sudden infant death syndrome (SIDS). This study showed that the age of 2 months appears to be a turning point in the development of digestive secretions, an age when the risk of SIDS is at its peak, and that the rates of the selected biological markers are significantly higher in victims of SIDS or ALTE than in controls. The predictive value of these biological markers is currently under evaluation.
Capillary (Heelstick) versus Venous Blood Sampling for the Determination of Glucose Concentration in the Neonate
Authors: Cowett Richard M. , D’Amico Lissa-Beth
Published: October 2009

Various sites may be used to obtain blood (plasma) for the determination of the glucose concentration in the neonate. Because multiple sites may be sampled in the same neonate, it is important to determine the variability in blood glucose concentration which may result from such sampling. Since pain and mechanical forces may be different because of the method used to obtain the capillary (heelstick) blood compared to the venous specimen, the two sites were sampled, and the blood glucose concentration was determined simultaneously in 25 asymptomatic well neonates whose mean birth weight was 2,562 ± 152 g and whose gestational age was 35.5 ± 1.5 weeks. There was a significant (p < 0.0001), but relatively weak correlation (r2 = 0.64) between capillary (heelstick) blood and venous blood relative to blood glucose concentration. When the capillary (heelstick)-venous glucose concentration difference was compared to the mean of the capillary (heelstick) and venous glucose concentrations, a difference of ± 0.5 mM (9 mg/dl) was noted in 3 of 25 neonates. Appropriately obtained capillary (heelstick) blood samples provide measurement of blood glucose concentration which are variable compared to venous samples, but which are probably not significant physiologically.
Consumption and Production of Amino Acids by Insulin-Responsive Cultured Fetal Rat Hepatocytes: The Particular Case of Serine
Authors: Bismut Hervé , Poggi-Bach Jo , Plas Christiane
Published: October 2009

The ability for 18-day fetal rat hepatocytes in primary culture to modify extracellular amino acid concentrations was studied between 24 and 48 h of culture. Most of the 19 amino acids tested were found to be taken up by the hepatocytes. However, serine and glutamate appeared in the 24-hour-conditioned medium to be twice as concentrated as in the fresh medium. The profile of net consumption or production of amino acids was unchanged when the medium was supplemented with essential amino acids. The use of [U-14C]glucose revealed that serine released in the medium was mainly formed from glucose. The presence of insulin (10 mM) did neither significantly modify the variations of amino acid concentrations in the medium nor 2-amino[l-14C]isobutyric acid uptake by the cells, while the hormone produced a 2-fold increase in glycogen labeling from [U-14C]glucose. This study revealed that whatever the regulatory culture conditions considered a net serine production out of the cells occurred, which appears to be specific to the fetal stage.
An Increased Ability to Generate Hydrogen Peroxide in Certain Polymorphonuclear Leukocytes in Neonates
Authors: Ueda Daisuke , Sakata Youko , Sasaki Kazuhiro , Azuma Hiroshi
Published: October 2009

We performed a quantitive assay of the hydrogen peroxide generation in polymorphonuclear leukocytes using single cell analysis by flow cytometry. The study population included premature neonates (n = 10), term neonates (n = 28) and healthy adults (n = 29). The ability to generate hydrogen peroxide in neonatal polymorphonuclear leukocytes was totally reduced compared with adults, however, some polymorphonuclear leukocytes in neonates demonstrated highly accentuated hydrogen peroxide generation.
Effects of Early Suckling of Cesarean-Born Babies on Lactation
Authors: Sözmen Melih
Published: October 2009

This study examines the effect of early suckling of mothers giving birth by cesarean section on milk ejection periods. Colostrum and milk ejection periods of 20 mothers who suckled their infants early and those of 20 who suckled late and provided supplementary food to their infants were observed. The colostrum and milk ejection periods of the early-suckled compared to the late-suckled group showed a significant statistical difference. The results show that the chance of the infants born by cesarean section of being fed by maternal milk could be increased by early and regular suckling of the maternal milk.
Urinary and Plasma Epidermal Growth Factor Levels Are Decreased in Neonates with Intrauterine Growth Retardation and in Their Mothers
Authors: Shigeta K. , Hiramatsu Y. , Eguchi K. , Sekiba K.
Published: October 2009

Epidermal growth factor (EGF) concentrations in urine and plasma samples collected from pregnant women and neonates were measured by RIA. The EGF concentration of the first voided urine was higher in appropriate-for-date (AFD) neonates (33.9 ± 23.0 ng/mg creatinine) than in those with intrauterine growth retardation (IUGR; 23.5 ± 7.7 ng/mg creatinine, p < 0.05) and heavy-for-date (19.8 ± 5.2 ng/mg creatinine, p < 0.05) neonates. The urinary EGF concentration of pregnant women showed no marked changes throughout pregnancy. Urinary EGF concentrations of women with AFD fetuses (45.9 ± 31.2 ng/mg creatinine) did not differ significantly from those of women with diabetes (39.9 ± 26.8 ng/mg creatinine) or women with multiple fetuses (44.6 ± 30.6 ng/mg creatinine). However, women with IUGR fetuses showed lower urinary EGF concentrations (13.8 ± 7.4 ng/mg creatinine, p < 0.05) than women with AFD fetuses. Maternal and fetal platelet poor plasma EGF concentrations at delivery were lower in the IUGR group (mother: 2.62 ± 0.38 ng/ml, fetus: 2.16 ± 0.07 ng/ml, respectively, p < 0.05 and p < 0.005) than in the AFD group (mother: 3.34 ± 0.64 ng/ml, fetus: 3.24 ± 0.93 ng/ml). In the IUGR group, the EGF concentration in fetal blood was always lower than that in maternal blood (p < 0.05), although the AFD group showed no such difference. These data suggest that EGF levels are closely related to fetal growth.
Developmental Changes of Glutamate Dehydrogenase Activity in Rat Liver Mitochondria and Its Enhancement by Branched-Chain Amino Acids
Authors: Eguchi Katsuto , Yonezawa Masaru , Mitsui Yukiteru , Hiramatsu Yuji
Published: October 2009

The developmental changes of glutamate dehydrogenase activity in the fetal and neonatal rat liver were investigated, as well as the effects of branched-chain amino acids on this enzyme. Hepatic glutamate dehydrogenase activity showed a marked increase at the end of the fetal period and peaked on the 5th day of neonate at approximately 3 times higher than the adult level. Glutamate dehydrogenase was activated by leucine, isoleucine, and valine in this order when they were added to isolated intact liver mitochondria in vitro. The enhancement of enzyme activity was more marked in fetal rats than in adults. In contrast, when branched-chain amino acids were added after disrupting the mitochondrial membrane by sonication, only leucine slightly activated glutamate dehydrogenase, while isoleucine and valine slightly inhibited its activity. Our findings suggest that glutamate may be actively synthesized in the developing rat liver mitochondria and then transaminated to other nonessential amino acids for protein synthesis, and that increased intramitochondrial branched-chain amino acid concentrations may enhance glutamate dehydrogenase activity. This anabolic metabolism will contribute to the fetal growth and development.
Development of Enzymes of Glycolysis and Gluconeogenesis in Human Fetal Liver
Authors: Sadava D. , Frykman P. , Harris E. , Majerus D. , Mustard J. , Bernard B.
Published: October 2009

The activities of two key enzymes of glycolysis and two key enzymes of gluconeogenesis were measured in liver samples from 44 human fetuses ranging in gestational age from 20 weeks to term, from infants to 10 years and from adults from 21 to 58 years. Specific activities of both gluconeogenic enzymes, fructose1,6-biphosphatase and phosphoenolpyruvate carboxykinase, increased throughout the period of fetal development examined, and rose to near adult levels after birth. The activities of both glycolytic enzymes, phosphofructokinase 1 and pyruvate kinase, were lower in fetal than in pediatric and adult samples. For both of these enzymes, there was a significant reduction in activity of livers from fetuses of 34–37 weeks’ gestation. Both enzymes showed hyperbolic kinetics at 24 weeks’ gestation, but this changed to sigmoid kinetics during the 34-37 weeks’ period of low activity. The data indicate that during the last weeks of gestation, inhibition of the activities of these two glycolytic enzymes, coupled with the rise in the two gluconeogenic enzymes, may reflect a change in liver from a primarily glycolytic role in the first two trimesters to a gluconeogenic role shortly before birth.
Urodilatin and Atrial Natriuretic Peptide Are Present in the Urine of Healthy Neonates and Young Infants
Authors: Bauer K. , Solc J. , Timnik A. , Solcova A. , Weil J.
Published: October 2009

Urine sampling has been proposed as noninvasive monitoring of plasma atrial natriuretic peptide (ANP) in neonates, assuming urine contains only filtered plasma ANP. Recently, urodilatin, another natriuretic peptide, which is cross-reactive to ANP in the ANP radioimmunoassay (ANP-RIA), has been isolated from the urine of adults. We studied the urine of healthy term neonates and young infants for the presence of urodilatin. In all urine samples, we found three peaks of ANP-RIA-reactive material: the first one in the position of urodilatin, the second one coeluting with synthetic ANP and a third late eluting peak, possibly containing degradation products. The physiological significance of these findings remains to be investigated.
Ontogeny of Intestinal Lipid and Lipoprotein Synthesis
Authors: Thibault Louise , Ménard Daniel , Loirdighi Nadia , Levy Emile
Published: October 2009

Despite increasing evidence that the fetal intestine produces apoproteins, there is limited knowledge about its ability to absorb fat. The present study focused on the intracellular processing of lipid formation and transport by lipoproteins in the developing fetus. Explants of fetal jejunum (14–20 weeks) were maintained in serum-free organ culture for 42 h with [14C]-oleate. Esterified lipids extracted from the tissue showed an abundance of phospholipids (PL; 54–77%), while those harvested from the medium displayed a predominance for triglycerides (TG; 68–73 %). Only a minor percentage of radioactivity was recovered in cholesterol ester (CE) from the tissue (1.8–2.5%) or medium (1.3–2.5%). Separation of PL by thin-layer chromatography revealed a prevalence of phosphatidylcholine followed by phosphatidylethanolamine. Over the fetal period studied a trend towards increase was noted in TG, CE and most of the PL classes but not phosphatidylcholine. In parallel, we observed a progressive increase in these lipoprotein fractions produced by the fetal intestine during development, i.e., chylomicrons, very low-density lipoproteins and high-density lipoproteins. Our data stress not only the ability of the fetal intestine to absorb fat, but also the ontogenetic changes of lipid and lipoprotein synthesis.
Measurement of Total Bodywater Volume with Deuterated Water in Newborn Infants
Authors: Baarsma R. , Hof P. , Zijlstra W.G. , Zock J.P. , Okken A.
Published: October 2009

D2O and H218O are often used as tracers for the determination of total body water (TBW). For newborn infants, the commonly used noninvasive method has not been validated. In this study TBW was calculated from D2O concentrations in blood and compared with TBW calculated from D2O concentrations in urine. TBW calculated from all urine portions voided at least 6 h after D2O administration on average was 1.0% lower. TBW calculated from only three urine portions voided 6, 12, and 24 h after D2O administration was 0.6% (mean) lower compared to TBW calculated from D2O concentrations in blood. This study indicates that the noninvasive method to measure TBW can be considered a reliable method when used in newborn infants.
GTP-Dependant Protein (Gs) Activity in Preterm Infants
Authors: Marguet C. , Basuyau J.P. , Brunelle Ph. , Fessard C. , Mallet E.
Published: October 2009

In a previous study, we showed a renal resistance to PTH in preterm infants during their 1 st week of life. We proposed it could explain early neonatal hypocalcemia. Such renal resistance is well known in type 1 pseudohypoparathyroid patients and is explained by a defect of stimulatory GTP-dependant protein (Gs). To determine if functional immaturity in the Gs protein could be involved in PTH resistance, we studied 27 newborn babies: 7 full-term and 20 preterm babies. Biological activity of the Gs unit was determined on days 1 3 and 10 after delivery by bioassay. No correlation was found between the Gs unit activity and either gestation or birth weight at these dates. Eight infants had hypocalcemia and their Gs unit activity did not differ from those with normocalcemia. Furthermore, we showed that the Gs unit is active from 29 weeks of gestation. We conclude that the Gs protein appears not to be involved in the pathophysiology of early renal resistance to PTH and therefore in early neonatal hypocalcemia.
Ovine Maternal and Fetal Glomerular Atrial Natriuretic Factor Receptors: Response to Dehydration
Authors: Fujino Yuji , Ross Michael G. , Ervin Gore , Castro Robert , Leake Rosemary D. , Fisher Delbert A.
Published: October 2009

In pregnancy, dehydration produces marked effects on maternal and fetal body water homeostasis including an increase in fetal urinary sodium concentration and excretion. To examine the role of fetal plasma atrial natriuretic factor (ANF) and glomerular ANF receptors in dehydration-induced natriuresis, we compared plasma ANF levels and glomerular ANF binding characteristics in dehydrated and control maternal and fetal sheep. Mean (± SEM) maternal and fetal plasma ANF levels in control animals (n = 9) at 132–136 days gestation were 37 + 3 pg/ml and 138 ± 20 pg/ml, respectively. Although mean ANF receptor maximum binding capacities (Bmax) were significantly higher in maternal than in fetal glomeruli (83 ± 11 vs. 34 ± 12 fmol/mg protein, respectively), the dissociation constants (Kd) for ANF binding were not different (2.7 ± 0.6 and 3.7 ± 1.7 × 10––10M, respectively). In an additional 9 animals studied after 63 ± 4 h of water deprivation, maternal plasma ANF levels were significantly lower than in the control group (14 ± 4 vs. 37 ± 3 pg/ml), maternal glomerular ANF receptor Bmax values were significantly higher (732 ± 203 vs. 83 ± 11 fmol/mg protein), and Kd values were six-fold higher (17.0 ± 7.1 vs. 2.7 ± 0.6 × 10––10M), although this difference was only marginally significant (p = 0.06). In contrast to the adult, there was a small, nonsignificant decrease in plasma ANF levels and no difference in Bmax or Kd values between the dehydrated and euhydrated fetal animals. These results indicate that the maternal ewe, like the adult rat, responds to dehydration with decreased plasma ANF levels and up-regulation of renal ANF receptors. The fetal lamb by contrast has increased plasma ANF levels and decreased renal glomerular ANF binding relative to the ewe, and fetal renal ANF binding characteristics are not affected by maternal dehydration. Thus, while changes in maternal plasma ANF and renal ANF receptors may partially explain maternal dehydration-induced natriuresis, the role of ANF in fetal dehydration-induced natriuresis remains unclear.
Effect of Dexamethasone on Antioxidant Enzymes in Fetal Rat Lungs and Kidneys
Authors: Asayama Kohtaro , Hayashibe Hidemasa , Dobashi Kazushige , Uchida Norihiko , Kato Kiyohiko
Published: October 2009

To determine if an enhancement in the fetal antioxidant enzyme (AOE) system by maternal dexamethasone (DEX) is specific to organ and dose, the lung and kidney of pups, whose mother received DEX (0.2 or 2 mg/kg) twice, were obtained on days 19 and 20 of gestation. Low-dose DEX increased the four AOE in the day-19 lung, but not in day-20 lung. High-dose DEX decreased the copper-zinc superoxide dismutase (SOD) and glutathione peroxidase in the lungs. Thus, the DEX-induced maturation of lung AOE is dependent on dose and timing. DEX enhanced the four AOE in the day-19 kidney at both doses. In the day-20 kidney, DEX enhanced the manganese SOD at the low dose and also catalase at the high dose, suggesting that DEX accelerates the maturation of kidney AOE as well.
Effect of Rat Atrial Natriuretic Factor on in vivo and in vitro Aldosterone and Corticosterone Secretions in the Rat during the Perinatal Period
Authors: Deloff S. , Leprêtre A. , Montel V. , Châtelain A.
Published: October 2009

The effect of rat atrial natriuretic factor (rANF) on aldosterone and corticosterone secretion was investigated in vivo in 21-day-old rat fetuses injected intravenously through the umbilical vein and in vitro on isolated adrenal cells from 17-, 19- and 21-day-old fetuses and 1-, 2-, 3- and 4-week-old rats. In vivo, rANF (50 pmol/50 µl/fetus) inhibited both basal levels and secretion of aldosterone stimulated by adrenocorticotropin hormone (ACTH(1–24), 0.25 pmol/50 µl/fetus), but not corticosterone secretion. In vitro, the addition of graded concentrations of rANF (0.001, 0.01 and 10 nmol/l) to the incubation medium did not affect the basal aldosterone and corticosterone secretions of fetal and neonatal adrenal cells. ACTH(1–24) (0.1 nmol/l) stimulated productions of both corticosterone and aldosterone by the adrenal cells at all stages studied. The addition of graded concentrations of rANF to the incubation medium containing ACTH(1-24) (0.1 nmol/l) induced a dose-dependent inhibition of aldosterone secretion by the adrenal cells from 21-day-old fetuses and newborn rats. In contrast, no effect was observed on cells from 17- and 19-day-old fetuses. At all stages investigated, the three doses of rANF were unable to affect ACTH-induced corticosterone secretion in vitro. In isolated adrenal cells from 2-week-old rats, rANF (10 nmol/l) inhibited the secretion of aldosterone induced by ACTH(1–24) (0.1 nmol/l), and by different steroids of the aldosterone synthetic pathway (progesterone, 11-deoxycorticosterone, corticosterone, 1µ mol/l for each steroid). These results suggest that rANF is a specific inhibitor of aldosterone synthesis in the perinatal period of the rat and that the inhibitory effect of rANF occurs both during the early and late pathways of aldosteroidogenesis.
Trophic Effects of Neurotransmitters during Brain Maturation
Authors: Emerit Michel B. , Riad Mustapha , Hamon Michel
Published: October 2009

Besides their neurotransmitter and/or neuromodulatory roles, many neuroactive substances synthesized and released during brain development can also directly influence neuronal differentiation. Transitory expression of neurotransmitters, their metabolic enzymes and their receptors is only one aspect of this trophic role. The most considerable progress in neurotrophic factor research has been made with the use of primary cultures of neuronal cells, and numerous studies have focused on the effects of neurotransmitters on the differentiation of cells at various stages of development. Thus, several neuropeptides like VIP, substance P, enkephalins, somatostatin, and monoamines, can modulate neuronal differentiation, but only during a limited period of fetal life. Among the monoamines, it was shown that, depending on the target, 5-HT stimulates the development of the neuropile, the myelinization of axons, the differentiation of the synaptic contacts, induces markers of monoaminergic neuron differentiation, inhibits the development of the growth cone, decreases the branching of neurites, and influences the survival, cell body size, and neurite outgrowth in several neuronal cultures. 5-HT can also indirectly influence the differentiation of serotonergic neurons by the intermediate of astrocytes, and it was shown in our laboratory that 5-HT1A agonists can stimulate the cholinergic parameters of primary cultures of rat fetal septal neurons. At the molecular level, the events triggered by neurotransmitters that underlie their neurotrophic action probably involve the transmembrane influx of calcium. To date, calcium regulation of cellular processes is one of the most rapidly expanding areas of research in developmental neurobiology.
Some Animal Models for the Study of Perinatal Asphyxia
Authors: Raju Tonse N.K
Published: October 2009

Much of our current understanding concerning the pathophysiology of perinatal brain disorders has evolved from animal studies over the past three decades. Fetal and neonatal nonhuman primate, pregnant sheep, lamb, puppy, piglet and immature rodents, all have been important animal models for perinatal brain research. Although no model can be considered Ê»perfect’ in reflecting the variety and complexity of human brain pathology, the investigator must assess the merits and limitations of each model within the framework of the research questions being asked. A variety of experimental designs have been used over the years and variations of particular interest are the animal age, the method of producing brain insult and the procedures used for evaluating outcomes. Most models relating to the study of intracranial hemorrhage, cerebral blood flow and cerebral energy metabolism have generally been acute preparations. Some important long-term survival models have also been developed in recent years for the study of hypoxicischemic encephalopathy. The latter include the nonhuman primate, piglet, sheep and immature rat models. In this article, I have reviewed some important animal models used in perinatal brain research with emphasis on those relating to perinatal asphyxia and intracranial hemorrhage.
Effect of Glucose on Perinatal Hypoxic-Ischemic Brain Damage
Authors: Vannucci Robert C. , Mujsce Dennis J.
Published: October 2009

Investigations suggest that hyperglycemia superimposed on hypoxia-ischemia or cerebral ischemia accentuates brain damage in adult experimental animals and humans. Such does not appear to be the case in immature animals. The present review discusses fundamental differences in immature and adult brain metabolism which account for the age-specific paradox. Based on currently available data, it is recommended that glucose supplementation not be curtailed during labor and delivery of asphyxiated human infants; on the contrary, glucose therapy might substantially reduce hypoxic-ischemic brain damage.
Effects of Anoxia and Aglycemia on the Adult and Immature Hippocampus
Authors: Ben-Ari Y.
Published: October 2009

Brief anoxic episodes induce a loss of consciousness due to an interruption of synaptic responses and repeated on more sustained episodes induce a selective neuronal loss in vulnerable regions notably in the CA1-H1 region of the hippocampus. The use of brain slices kept in vitro has considerably improved our understanding of the mechanisms underlying anoxia and ischemia and the strategies of development of protective drugs or manipulations. This report reviews our present understanding of the effects of anoxiaischemia on neuronal activity in particular concerning the abrupt and major changes in vulnerability which occur with maturation of the brain.
Ischaemia of the Preterm Brain
Authors: Greisen Gorm
Published: October 2009

Much has been learned about the diagnosis and prognosis of periventricalar leucomalacia during the past 10 years. The understanding of its causation, however, has not advanced much. Still, the candidate for the principal role is focal ischaemia in the particularly vulnerable regions of the brain. It has been difficult to provide direct supportive evidence for this hypothesis. It has not been possible to define a threshold for (global) cerebral blood flow (CBF) under which brain damage or electrical dysfunction occurs. Three hypothetical explanations for the lack of clear relation between global CBF and electrical brain activity of the preterm infant must be examined more closely: (1) the very low levels of CBF are adequate, (2) global CBF does not reflect the perfusion of the white matter, or (3) acute white-matter ischaemia does not result in cerebro-electrical dysfunction. In view of the practical importance, more research is indicated.
Perinatal Pharmacology and Cerebral Blood Flow
Authors: Saliba E. , Autret E. , Nasr C. , Sue A.L. , Laugier J.
Published: October 2009

Many of the drugs used in neonatal intensive care units might impede cerebral blood flow, thereby increasing the risk of intraventricular hemorrhage and periventricular leukomalacia. Our studies focussed on sick preterm neonates who were treated with the following drugs: caffeine (20 mg/kg i.v., as caffeine citrate); phenobarbital (loading dose: 20 mg/kg); indomethacin (0.2 mg/kg/dose, every 12 h three doses), and synthetic surfactant (Exosurf; 50 mg/kg = 5 ml/kg intratracheally). All of the drugs studied, except indomethacin, had no adverse effect on cerebral hemodynamics.
Hemodynamic Foundation of Umbilical Arterial Doppler Waveform Analysis
Authors: Maulik Dev , Arbeille Philippe , Kadado Taha
Published: October 2009

This paper reviews various in vitro and in vivo studies which have been conducted to investigate the influence of central and peripheral circulatory factors on the Doppler indices. These studies indicate that the Doppler indices are affected by both central and peripheral hemodynamics. Of the central factors, the heart rate influences the indices predominantly through the variations during the diastolic phase of the cardiac cycle. This was confirmatory of the clinical findings. Of the other central factors, cardiac contractility may not affect the rising slope of the Doppler waveform. Regarding the peripheral hemodynamics, both in vitro and in vivo studies confirm that the indices reflect the changes in the peripheral resistance; however, opposition to flow in a pulsatile flow can be adequately described only by impedance. Initial in vivo and in vitro studies demonstrate that the indices correlate well with the impedance parameters. However, this is true only when the central circulation remains stable.
Growth Velocity of Some Fetal Parameters
Authors: Guihard-Costa Anne-Marie , Larroche J.Cl.
Published: October 2009

In this study, fetal growth velocities of the brain weight (whole brain and infratentorial part) and of the right and left fronto-occipital diameters were established from 420 normal fetuses and neonates. The age of the subjects ranged from 10 to 41 gestational weeks. Growth rates were computed by time intervals, and velocity curves were plotted with their 95% confidence intervals. The whole brain displays an accelerating pattern of growth until 35 weeks; thereafter, the growth rate breaks down. The growth velocity of the infratentorial part of the brain increases throughout fetal life, without a fall at 35 weeks. Moreover, it grows faster than the whole brain after 24 weeks. The lengths of the hemispheres present a steady decreasing pattern of growth velocity throughout pregnancy.
Effects of Injectable β-Carotene and Vitamin A on Lymphocyte Proliferation and Polymorphonuclear Neutrophil Function in Piglets
Authors: Hoskinson C.D. , Chew B.P. , Wong T.S.
Published: October 2009

Newborn piglets were injected with either (1) vehicle; (2) 20 mg β-carotene; (3) 40 mg β-carotene; (4) 25,000 IU vitamin A palmitate, or (5) 50,000 IU vitamin A palmitate. Blood was collected at 0.5, 1, 3, and 6 weeks of age and lymphocyte proliferation, polymorphonuclear neutrophil (PMN) phagocytosis and intracellular killing of live Escherichia coli were measured. Lymphocyte proliferation in all piglets was high at birth but decreased thereafter. Piglets injected with either high β-carotene or vitamin A palmitate showed higher phytohemag-glutinin- and pokeweed mitogen-induced lymphocyte proliferation at week 3 compared to controls. Similar results were seen with 20 μg/ml concanavalin A in piglets injected with high vitamin A palmitate. Phagocytosis by PMN isolated from all piglets decreased to a nadir at week 3 but returned to values observed in the newborn by week 6. Lreatment had no effect on phagocytosis. Piglets injected with β-carotene or vitamin A palmitate had lower intracellular killing ability at week 3 compared to controls. Therefore, β-carotene and vitamin A palmitate enhanced mitogen-induced lymphocyte proliferation but reduced killing ability by PMN in piglets.
Effects of Interleukin-3 on Murine Fetal Liver Hemopoiesis in utero
Authors: Delorme Danielle , Daniels Eugene
Published: October 2009

The normal regulation of primitive hemopoietic stem cells (PHSCS) throughout development involves locally produced factors and humoral factors. While considerable information is available on the effects of candidate hemopoietic growth factors (HGFs) on postnatal hemopoietic tissues, little is known about the regulatory events of developing hemopoietic stem cells within fetal microenvironments. Fetal hemopoiesis represents expanding populations and may be under different regulatory control mechanisms. The microinjection of purified interleukin-3 (IL-3), a candidate HGF, into 13-day-old mouse fetuses via the yolk sac, allowed us to evaluate its effects on morphogenetic events and, more specifically, on fetal liver populations using quantitative in vitro clonal assays for hemopoietic precursors. In view of the sensitivity of fetal development during the early organogenetic period, considerable care was taken to identify the stress effects of the surgical laparotomy and the microinjection procedure. Control studies, required to distinguish stress effects of surgical laparotomy and microinjection, clearly revealed that the fetal liver is a sensitive organ responding with limited tissue disorganization, reduced cellularity and erythropoietic activity, as monitored 24 h after experimental intervention. The microinjection of 15 units of IL-3 promoted a significant expansion of depleted liver hemopoietic-cell populations and had stimulatory effects on the distribution of connective tissue mast cells and absolute cell numbers, including hemopoietic precursors (erythroid, granulocyte, macrophage, megakaryocyte), compared to controls. These studies suggest that (1) fetal liver hemopoiesis is selectively sensitive to maternal stress but has an effective regenerative capacity to maintain essential hemopoiesis in utero, and (2) fetal hemopoietic cells acquire an ability to respond to IL-3 early in fetal development.
Ontogeny of Gastric Function in the Pig: Acid Secretion and the Synthesis and Secretion of Gastrin
Authors: Sangild Per T. , Cranwell Peter D. , Hilsted Linda
Published: October 2009

Gastric acid secretion, gastrin-releasing peptide (GRP)-stimulated gastrin secretion and concentrations of somatostatin in gastric tissues were studied in sucking pigs (n = 48). In addition, gastrin concentrations in plasma and antral tissue were measured in fetal and sucking pigs (n = 66) from 22 days before birth (93 days gestation) to 36 days of age. From 3 days of age littermate pairs were treated twice a day with either saline (n = 20) or adrenocorticotropin [ACTH (1–24); n = 20]. Pentagastrin-stimulated acid secretion per unit stomach weight was 39 ± 7 μmol H+/g/h at 0–1 day, increased to 194 ± 15 μmol H+/g/h at 5–7 days and plateaued. Antral gastrin concentration was 0.14 nmol/g 10 days before birth and increased to 2.7 nmol/g at 5 weeks of age. Plasma gastrin was 25 ± 2 pmol/l at 22 days before birth, increased to 102 ± 14 pmol/l at birth and decreased during the postnatal period. Somatostatin concentrations were higher in antral than fundic tissues (p < 0.05) and remained constant during the postnatal period. Increased levels of glucocorticoids in plasma following ACTH treatment had no effect on the studied parameters except that it reduced basal (p < 0.07) and GRP-stimulated (p < 0.05) plasma gastrin concentrations at 6–7 days of age. Development of acid secretion and its gastric regulatory peptides in the pig is different from that in the rat in that it occurs at an earlier age and does not appear to be greatly influenced by elevated glucocorticoid levels from 3 days after birth.
Effect of Vitamin K on Neonatal Erythrocytes
Authors: Shahal Yael , Zmora Ehud , Katz Miriam , Mazor Dalia , Meyerstein Naomi
Published: October 2009

This study investigated the possible oxidative effect of vitamin K3 (menadione) and Vitamin K1 (Konakion) on neonatal erythrocytes by controlled in vitro exposure. Menadione caused only mild morphological changes and did not decrease ATP levels. However, it oxidized intracellular hemoglobin to methemoglobin in neonatal cells more than in adult cells. Reduced glutathione contents were higher in neonatal cells, but less available for antioxidant protection. Konakion did not increase methemoglobin levels in newborn infants after a prophylactic injection. In vitro exposure to Konakion did not affect reduced glutathione and ATP levels, nor did it oxidize hemoglobin. However, extensive morphological changes were observed, attributed to the effect of its solvent. Therefore, it seems that menadione, which is no longer administered to newborns, causes oxidative stress in neonatal cells whereas Konakion, the current vitamin K1, does not, either in in vitro studies or by therapeutic administration.
Sialic Acid Level in Maternal and Neonatal Lymphocytes and Sera Correlated to Birth Order and Sex of the Neonate
Authors: Komlos L. , Landmann J. , Notmann J. , Dulitzky F. , Kyzer S. , Hart J. , Halbrecht I. , Levinsky H.
Published: October 2009

Sialic acid (N-acetylneuraminic acid) was determined 1 h after normal term deliveries on peripheral blood lymphocytes from 42 mother-neonate pairs and in 29 maternal and neonatal sera. Results were evaluated according to maternal parity and sex of the neonate. The cases were divided into two groups: primiparae, and secundi- and multiparae. In primiparae the sialic acid level on lymphocytes from male neonates and from their mothers was by 23–30% decreased as compared to female neonatal and maternal cells. In the higher parity group, a significantly increased sialic acid level was found on lymphocytes from male as compared to female neonates, and maternal serum sialic acid concentration, unrelated to the newborns’ sex, was by 17–20% increased as compared to primiparae. The results suggest that with increasing parity higher levels of sialic acid on male neonatal cells may possibly contribute to mask fetal male-specific histocompatibility antigens. Increased sialic acid levels in maternal sera from secundi- and multiparae suggest its possible contribution to an increased serum blocking effect.
In vivo Activated Cord Blood Lymphocytes Express High Affinity lnterleukin-2 Receptor: Evaluation of Their Responsiveness to in vitro Stimulation with Recombinant lnterleukin-2
Authors: Montagna D. , Moretta A. , Marconi M. , Mingrat G. , Gasparoni A. , Giarola M. , Maccario R.
Published: October 2009

We report the phenotypical and functional characterization of a cord blood mononuclear lymphocyte subset (CBMC) which expresses the p55 chain of interleukin-2 receptor (IL-2R, CD25). The great majority of CD25-positive CBMC are activated CD3-positive T lymphocytes in that most of them are HLA-DR-positive, coexpress both CD4 and CD8 antigens and at least a part of them display high affinity IL-2R. In keeping with the expression of both chains of IL-2R (p55 and p75), enriched CD25-positive CBMC are able to display strong IL-2-induced proliferation and lymphokine-activated killing activity. The percentage of CD25-positive cells is higher in cord blood than in adult peripheral blood and their presence could be peculiarly important in the neonatal period, when specific T-cell-mediated immune responses are still on their way to full maturation.
Developmental Changes of Polyamine Biosynthesis in Rat Liver
Authors: Eguchi Katsuto , Yonezawa Masaru , Ohmoto Hiroyuki , Mitsui Yukiteru , Hiramatsu Yuji
Published: October 2009

To investigate the role of polyamine metabolism in fetal development, we determined the hepatic polyamine content and the activity of enzymes related to polyamine metabolism in fetal, newborn and adult rats. In the fetuses, spermidine was detected at the highest level, followed by spermine and then putrescine. Putrescine and spermidine levels were higher in the fetuses than in adult rats, while the spermine level was significantly lower in the fetuses. The activities of the enzymes investigated were also higher in the fetuses than in adult rats. These findings indicate that polyamine synthesis was enhanced in the fetal liver, and that degradation of spermidine via spermidine N1-acetyltransferase contributes to the increase in putrescine levels. Thus, our study suggests that an increase in putrescine is important for fetal growth and that putrescine per se has a significant role in fetal cellular proliferation.
Abnormal Cortical Plate (Polymicrogyria), Heterotopias and Brain Damage in Monozygous Twins
Authors: Larroche J.Cl. , Girard N. , Narcy F. , Fallet C.
Published: October 2009

We report 5 cases of abnormal cortical plate (polymicrogyria or microgyric-like pattern) and heterotopias associated with hypoxic-ischemic brain injuries in monochorionic diamniotic twin fetuses of respectively 22, 26, 28, 31, 32 weeks gestation. These fetuses belonged to a series of 5 pairs of patients (10 cases) presenting with the characteristic features of the twin-to-twin transfusion syndrome. Three of them (2 donors and 1 recipient) were macerated and the brains were not available for study. Two (most likely recipient twins) survived. In the remaining 5 fetuses (3 donors and 2 recipients) with neuropathological study there were cortical plate abnormalities. In 2 cases, the cortex was dysmorphic and consisted of focal nodular distribution or vertical stripes of neurons. True polymicrogyria was focal in 2 cases and involved almost the entire surface of the hemispheres in another one. Heterotopias of immature cells were found in 4 cases, either in the white matter or in the cortex or in both sites. There was a focal laminar necrosis only in 2 cases. The morphological pattern of the anomalies depends on the time of occurrence of the insult and on its severity. These abnormalities, although similar to those already described in singleton fetuses, illustrate the variety of cortical dysmorphia which may be associated with fetal hypoxic-ischemic injuries and emphasize the particular vulnerability of the brain in monozygotic twins, whether it belongs to the donor or the recipient.
Urinary Growth Hormone Excretion in Preterm Neonates
Authors: Tsukahara Hirokazu , Fujii Yasushi , Kuriyama Masanori , Tsuchida Shinya , Hiraoka Masahiro , Kikuchi Kiyoshi , Sudo Masakatsu
Published: October 2009

We measured urinary growth hormone (U-GH), β2-microglobulin (U-B2) and serum growth hormone (S-GH) in preterm neonates on days 1 4, 7, 14 and 28 of age. U-GH as well as U-B2 were high, particularly in the more premature and sick neonates with respiratory failure requiring mechanical ventilation. U-GH showed significant positive correlations with U-B2 throughout the study but with S-GH only on day 7. Therefore, we conclude that in preterm neonates, U-GH mainly reflects the degree of renal proximal tubular function, which is determined by the degree of renal maturation of the subject and of tubular injury due to disease states such as respiratory failure.
Ornithine Decarboxylase Activity and Urea in Liver of Late-Pregnant Rats
Authors: Poveda B. , Soler C. , Soley M. , Pastor-Anglada M.
Published: October 2009

It has been suggested that the induction of ornithine decarboxylase (ODC) activity during pregnancy might contribute to the low ureagenic flux that enables the pregnant mother to spare nitrogen and support growth. Thus, we have studied the ODC activity, and urea and polyamine levels in livers of virgin and 21-day pregnant rats, either in a basal state or after the induction of ureagenesis by inducing diabetes in rats by streptozotocin injection. Diabetes led to a marked increase in circulating and liver urea levels in virgin rats. This response was significantly reduced in late-pregnant animals. Diabetes did not modify ODC activity in pregnant rats, which showed much lower activities than their virgin controls. Diabetes caused a depletion of the liver spermine content in pregnant rats. Spermidine levels were higher in both groups of pregnant animals than in their respective controls. Our results suggest first that the mechanisms contributing to spare nitrogen in the pregnant mother are likely to be present in diabetic pregnant animals and, second, that ODC does not mediate the metabolic adaptations leading to a low ureagenic flux and a higher nitrogen retention at the last stage of pregnancy.
Secretin Induces Precocious Cessation of Intestinal Macromolecular Transmission and Maltase Development in the Suckling Rat
Authors: Harada E. , Syuto B.
Published: October 2009

The effect of endogenous and exogenous secretin on the intestinal closure of macromolecular transmission and maltase development were investigated in suckling rats. The increase in secretin-like immunoreactivity with orogastric infusion of HCl solution in 14 day-old pups was confirmed. By the repeated oral administration of HCl, pancreatic hyperplasia, suppression of intestinal bovine IgG transmission, and precocious induction of maltase activity were occurred. By repeated subcutaneous injection of secretin, dose-dependent suppression of intestinal bovine IgG absorption and increase in maltase activity were observed. The suppression of IgG absorption with secretin treatment was also observed in adrenalectomized pups. These results suggest that secretin affects the maturation of gastrointestinal function in suckling rats.
Elevated Venous Concentrations of Vasoactive Intestinal Polypeptide in Cord Blood of Infants with Fetal Distress
Authors: Ishitani Nobuo , Ohzeki Takehiko , Hanaki Keiichi , Motozumi Hiroko , Sunaguchi Mayumi , Shiraki Kazuo
Published: October 2009

Concentrations of vasoactive intestinal polypeptide (VIP) in cord plasma were determined in 70 neonates (birth weight, mean ± SD, 3,213.5 ± 50.9 g, gestation 39.5 ± 0.2 weeks), 22 of whom had fetal distress. Arterial VIP levels in cord blood were not significantly different between infants with and without fetal distress. The mean venous VIP in cord blood of distressed infants (28.1 ± 8.4pg/ml, mean ± SE) was significantly (p < 0.05) higher than that of normal neonates (12.6 ± 3.4pg/ml). The mean placental content of VIP was 5.1 ± 0.3 ng/g wet tissue, although a correlation with the venous concentration in the cord was not demonstrated. Venous VIP levels were elevated 24 h after birth (34.6 ± 13.7 pg/ml) and decreased on the 5th day of life to 12.9 ± 3.8 pg/ml, which was not significantly different from the mean VIP level in childhood (14.7 ± 3.1 pg/ml). These results demonstrate that, in the perinatal period, plasma VIP levels are elevated on two occasions: at delivery associated with fetal distress (cord vein), and at 24 h of age. VIP in the former seems to be of placental and/or maternal origin.