bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Magnesium Sulfate on Kidney Function in the Newborn Rabbit
Authors: Brenna S. , Thonney Viani M. , Drukker A. , Guignard J.-P.
Published: April 2003

The aim of this study was to investigate the acute, short-term effects of the intravenous (i.v.) administration of magnesium (Mg) sulfate on renal function in the newborn rabbit. Eight anesthetized and mechanically ventilated, normoxemic, newborn New Zealand white rabbits were studied. We measured mean arterial blood pressure (MAP), urine volume (V), glomerular filtration rate (GFR), renal plasma flow (RPF) and calculated renal blood flow, filtration fraction (FF) and renal vascular resistance (RVR) under control conditions and in two experimental periods after the i.v. Mg sulfate load. Mg sulfate administration in a dose 100 mg/kg followed by 50 mg/kg/h caused a significant fall (p < 0.001) in MAP, GFR and RPF, whereas the RVR increased (p < 0.01). FF did not change significantly (p: NS/0.05) and V remained constant. These results show that the acute i.v. administration of Mg sulfate to newborn rabbits causes systemic vasodilatation with a fall in MAP. The increase in RVR, without consistent change in FF, suggests that the renal vasculature of the ‘immature’ neonatal rabbit reacts to these changes by preferential afferent arteriolar vasoconstriction.
Reduced Capacity of Neonatal Lymphocytes to Inhibit the Growth of Candida albicans
Authors: Shareef Maliha J. , Myers Thomas F. , Mathews Herbert L. , Witek-Janusek Linda
Published: April 2003

Opportunistic microorganisms produce significant morbidity and mortality in preterm and term infants. Because of the heightened susceptibility of infants to opportunistic fungal infections, neonatal lymphocytes were assessed for their capacity to inhibit the growth of Candida albicans. Lymphocytes from both preterm and term cord blood demonstrated significantly less effect upon C. albicans than did lymphocytes from adults. Neonatal lymphocytes of infants <32 weeks of gestation showed a marked reduction in growth inhibitory capacity compared to infants >32 weeks of gestation. Lymphocytes from female infants had a significantly greater fungal growth inhibitory capacity than did lymphocytes from male infants. These results show that neonatal lymphocytes have a reduced capacity to inhibit the growth of C. albicans. This reduced antifungal capacity may underlie the increased susceptibility of such infants to opportunistic microorganisms, like C. albicans.
Complications of Airway Management in Very-Low-Birth-Weight Infants
Authors: da Silva Orlando , Stevens D.
Published: April 2003

Objective: To define the incidence of complications of endotracheal intubation and the factors associated with these complications. Study Design: During a 22-month period, 227 intubated infants weighing <1,501 g were followed prospectively in a neonatal intensive care unit. Detailed records of events associated with airway management were kept after every intubation, in addition to clinical data. Results: Eleven infants (4.8%) developed respiratory stridor after extubation which was treated with either systemic corticosteroids, racemic epinephrine and/or reintubation for respiratory failure. Four infants were submitted for bronchoscopy, mild subglottic stenosis with tracheal edema was found in 1 patient, granulation tissue and airway edema were noted in 3 infants. Traumatic intubation, prolonged ventilation, multiple intubations and bacterial colonization of the endotracheal tube were the factors associated with postextubation stridor. Conclusions: Subglottic stenosis is an infrequent complication of endotracheal intubation with current airway management of very-low-birth-weight infants. Less severe complications are still common, but they are usually amenable to clinical treatment. Bronchoscopy should be performed selectively only in infants with clinical evidence of airway obstruction after extubation.
Development of Rat Embryos Cultured in Serum from Diabetic Rats
Authors: Menegola Elena , Broccia Maria Luisa , Prati Mariangela , Giavini Erminio
Published: April 2003

Experimental studies carried out in vitro suggest a role of oxidative stress in diabetes-induced embryopathies. Glutathione is the main defense against free radicals in embryonic as it is in adult tissues. In this experiment, using postimplantation whole-embryo culture, we analyze: (1) the effects of serum from streptozotocin-induced diabetic rats on embryonic development and on glutathione distribution between the yolk sac and embryonic tissues and (2) the role of glutathione in preventing embryopathies (using the inhibitor of glutathione synthesis buthionine sulfoximine). Our data show that in rat embryos cultured in diabetic serum, the only observed effects are at the yolk sac level. No effects on the glutathione content were observed. The addition of buthionine sulfoximine reduced the glutathione content and produced signs of developmental delay in embryos cultured in diabetic serum, suggesting a role of the oxidative stress in producing
diabetes-related embryotoxicity.
Elastin of the Umbilical Cord Arteries and Its Alterations in EPH Gestosis (Preeclampsia)
Authors: Pawlicka Elżbieta , Bańkowski Edward , Jaworski Stefan
Published: April 2003

Edema, proteinuria, hypertension (EPH) gestosis is accompanied by an increase of collagen content and premature replacement of hyaluronic acid by sulfated glycosaminoglycans both in the umbilical cord arteries and in Wharton’s jelly. The effect of EPH gestosis on elastin content and metabolism in the umbilical cord arterial wall was the aim of this work. Studies were performed on normal umbilical cord arteries and those taken from newborns of mothers with EPH gestosis. Elastin was isolated from the arterial wall and quantified by a dye-binding method. Biosynthesis and degradation of this protein was evaluated by a pulse-chase experiment with the use of 14C-proline. It was found that EPH gestosis is associated with a significant reduction of elastin content in the umbilical cord arteries as a result of decrease in elastin biosynthesis rate and accelerated degradation of this protein. The replacement of elastin by collagen, and hyaluronate by sulfated glycosaminoglycans, may decrease the hydration of arterial wall and reduce its elasticity. Such rearrangement of extracellular matrix of the umbilical cord arteries may affect mechanical properties of these vessels and disturb fetal blood circulation.
Effect of Age and Weaning on Gastric Mucosal Injury in Developing Rats
Authors: Kaneko Hiroaki , Tabata Masahiko , Tomomasa Takeshi , Morikawa Akihiro
Published: April 2003

We evaluated ethanol- and HCl-induced mucosal damages in developing rats. The degree of damage induced by ethanol and HCl was greatest in 1-week-old rats and decreased significantly with age until 4 weeks; thereafter it increased again. To evaluate the effect of weaning on the maturational changes in mucosal defense, we compared ethanol-induced mucosal damage among three groups of newborn rats: (1) receiving milk only; (2) receiving only rat chow from 14 days of age, and (3) having free access to milk and chow. There were no significant differences at 18 and 21 days of age. The mucus thickness increased with age until 8 weeks and was not affected by weaning. In conclusion, developmental changes occur in gastric mucosal protection in rats. Weaning does not have a significant effect on these changes.
High-Frequency Oscillatory Ventilation, Partial Liquid Ventilation, or Conventional Mechanical Ventilation in NewbornPiglets with Saline Lavage-Induced Acute Lung Injury
Authors: Degraeuwe Pieter L.J. , Thunnissen Frederik B.J.M. , Vos Gijs D. , Blanco Carlos E.
Published: April 2003

It has been reported that, in diseased lungs, either partial liquid ventilation (PLV) or high-frequency oscillatory ventilation (HFOV) can improve oxygenation better and with less lung injury than conventional mechanical ventilation (CMV). This study was intended as a preclinical comparison between the effects of HFOV, PLV and CMV on gas exchange, lung mechanics and histology. Fifteen anesthetized newborn piglets, with respiratory insufficiency due to repeated saline lung lavage, were allocated to either a PLV, HFOV or CMV (n = 5 each) strategy, and treated for 4 h. Within 30 min of commencing therapy, PLV, HFOV, and CMV improved arterial Po2 (Pa,o2), alveoloarterial oxygen gradient (P(A-a),o2), oxygenation index (OI), venous admixture (va), and arterial Pco2 (Pa,co2). After 4 h, oxygenation parameters (Pa,o2, P(A-a),o2, OI and venous admixture) were significantly better in the HFOV group than in the PLV group; the CMV group showed a higher Pa,o2 and lower OI than the PLV group. Gas exchange at the end of the experiment was not different from baseline in the HFOV and CMV groups. Lung histology and morphometry were performed after perfusion-fixation at endotracheal deflation pressure corresponding to mean airway pressure at the end of the experiment. Lung injury score and mean linear intercept were not different between the three treatment groups. We conclude that in this model, gas exchange improved significantly in all three ventilation strategies. Indices of oxygenation improved less during PLV. The saline lavage-induced acute lung injury model used as in this study, is less stable than previously thought. The final lung injury is not influenced by the ventilation strategy. We speculate that the impaired gas exchange during PLV is an expression of diffusion limitation and ventilation-perfusion mismatch in a recovering lung.
Changes in Cerebrospinal Fluid Monoamine Metabolites, Tryptophan, and γ-Aminobutyric Acid during the 1st Year of Life in Normal Infants
Authors: Cann-Moisan C. , Girin E. , Giroux J.D. , Le Bras P. , Caroff J.
Published: April 2003

Cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, homovanillic acid, tryptophan, and γ-aminobutyric acid were measured using high-performance liquid chromatography in 102 infants during the 1st year of life (preterm and term neonates included). CSF levels are expressed versus corrected age (postnatal days – preterm days) which reflects the stage of maturity of the central nervous system. These results are compared to those obtained in CSF of 53 victims of sudden infant death syndrome (SIDS). All components were significantly higher in SIDS than in the age-matched control group. This increase does not seem to be an artefact related to death. Indeed, under the same conditions concerning postmortem time interval before CSF sampling and analysis, the levels are not significantly higher in infants who died from a known pathology than in living infants. Moreover, in living infants as regards a pathology such as asphyxia or hypoventilation in comparison with SIDS, similar profiles are observed in some neurotransmitters or metabolites. Other studies are necessary to explore further neurotransmission systems in SIDS.
Postnatal Changes of Leptin Levels in Full-Term and Preterm Neonates: Their Relation to Intrauterine Growth, Gender and Testosterone
Authors: Ertl Tibor , Funke Simone , Sárkány Ilona , Szabó István , Rascher Wolfgang , Blum WernerF. , Sulyok Endre
Published: April 2003

The present study was carried out to investigate leptin levels in arterial and venous cord serum and in amniotic fluid in full-term infants at birth and on the 5th postnatal day to define the relationship of leptin to intrauterine growth rate, gender and early postnatal life. The relation of weight gain to serum leptin levels in male preterm infants was determined measuring leptin concentration weekly in the first 5 postnatal weeks. Testosterone levels were determined simultaneously to explore a possible relationship between leptin and testosterone concentrations.Fifty-three term newborn infants with mean birth weight and gestational age of 3,419 g (range 2,150–4,480) and 38.9 weeks (range 36–41) and 19 preterm male infants (mean birth weight and gestational age were 1,416 g (770–1,800) and 30.2 weeks (26–35) were enrolled into the study. Leptin and testosterone levels were determined by radioimmunoassay. It was demonstrated that serum leptin levels were markedly elevated in the cord blood without discernible arteriovenous differences. Cord blood leptin was found to correlate with birth weight (r = 0.40, p < 0.002), weight to length ratio (r = 0.40, p < 0.002) and body mass index (r = 0.35, p < 0.005). It was significantly lower in boys as opposed to girls (p < 0.01) and there was an apparent fall by the 5th postnatal day (p < 0.001). Amniotic fluid contained leptin in much less concentration than cord blood and it proved to be independent of intrauterine growth or gender. Serum leptin concentration in preterm infants at 1 week of age was significantly lower compared with term infants (p < 0.002) and it increased progressively with age (p < 0.01). An inverse relationship was found between leptin and testosterone level (r = –0.358, p < 0.01) and a positive correlation between leptin level and weight/height ratio (r = 0.674, p < 0.01).It is concluded that leptin derived either from placenta or fetal adipose tissue may be involved in regulating fetal growth and development and it may be related to energy intake, storage and expenditure. In preterm male infants serum leptin concentration increases with postnatal weight and testosterone may suppress leptin synthesis.
Changes in Rat Papilla Microsomal Membrane Fluidity during Development
Authors: D’Antuono CeciliaL. , Sterin-Speziale NormaB.
Published: April 2003

During maturation, rat renal papillary microsomes suffer a rearrangement in their fatty acid phospholipid composition. The most significant changes in total phospholipids are the increase in their content of the 20:4 and a decrease in the levels of 14:0, 16:0, 18:1, 22:6 and 20:3 fatty acids. The changes in total phospholipid fatty acid content are a reflection of the variations in the individual phospholipid composition. During this period, microsomal cholesterol, phospholipid, and protein concentrations present no variations. Steady state fluorescence anisotropy obtained by using TMA-DPH (see text) as a fluorescence probe denoted higher values for 70- versus 10-day-old microsomes. Using DPH as a probe, steady state fluorescence anisotropy was determined in whole microsomes, as well as in total lipid and phospholipid vesicles, from both 10- and 70-day-old papillary cells. No differences were detected in phospholipid and total lipid vesicles between days 10 and 70. On the other hand, 10-day-old microsomes appeared to be less fluid than adult microsomes. The results indicate that these structural changes in kidney membranes during development might affect protein-lipid interaction and, therefore, the activity of many membrane enzymes.
Fetal Hepatic Oxygen Consumption under Normal Conditions in the Fetal Lamb
Authors: Holcomb RobertG. , Wilkening RandallB.
Published: April 2003

Previous measurements of fetal hepatic blood flow have relied on microsphere methodology. Estimates of fetal hepatic oxygen consumption (VO2), based on these measurements and the oxygen content difference across the fetal hepatic circulation, have been quite variable. To estimate hepatic VO2 in the fetal lamb by a different methodology, we applied the Fick principle using the steady-state uptake of indocyanine green (ICG) by the fetal liver to measure left hepatic blood flow in 10 pregnant ewes. Sampling catheters were inserted into the fetal external iliac artery, left hepatic vein, and umbilical vein. ICG was infused to steady state (for approximately 60 min) through a fetal brachial vein. Four sets of ICG concentration differences across the circulation of the left hepatic lobe were determined for each animal, and left hepatic lobe blood flow calculated. The oxygen concentration difference was measured simultaneously and VO2 of the left hepatic lobe calculated. In addition, we measured fetal VO2 and calculated the ratio of hepatic to fetal VO2. Left hepatic lobe blood flow was 382.30 ml/min/100 g tissue (COV = 0.32), a result statistically no different than in 4 animals with an independent measurement of hepatic blood flow using an ethanol equilibration method. Hepatic VO2 was 1.74 μmol/min/g tissue (COV = 0.13), and hepatic to fetal VO2 ratio was 18.23% (COV = 0.19). Our results indicate that normal fetal hepatic oxygen uptake per gram of tissue is less variable than previously suggested, and that ICG can be applied in the fetus for the purpose of hepatic blood flow measurement.
Efficacy of Anti-Tumor Necrosis Factor-Alpha Antibody as an Adjunctive Therapy in Experimental Escherichia coli Meningitis in the Newborn Piglet
Authors: Park Won Soon , Chang Yun Sil , Ko Sun Young , Kang Mi Jung , Han Jung Mie , Lee Munhyang
Published: April 2003

This study was done to evaluate the efficacy of anti-tumor necrosis factor alpha (anti-TNF-α) antibody as an adjunctive therapy in neonatal bacterial meningitis. Newborn piglets were divided into three groups: 8 in the control group, 13 in the meningitis group (MG), and 10 in the meningitis with anti-TNF-α antibody group (AG). Meningitis was induced by intracisternal injection of 108 colony-forming units of Escherichia coli in 100 μl of saline. In the AG, 200 μl of anti-TNF-α antibody was also given intracisternally. In the AG, the elevated cerebrospinal fluid TNF-α level observed in the MG was completely abolished, and increased intracranial pressure, hypoglycorrhachia, and CSF pleocytosis observed in the MG were downmodulated. But blood, brain, and CSF lactate levels remained elevated in both MG and AG. Increased brain cell membrane lipid peroxidation products and decreased Na+,K+-ATPase activity observed in the MG were not attenuated in the AG. These results indicate that anti-TNF-α antibody was not particularly effective as an adjunctive therapy in attenuating acute inflammatory responses and ameliorating brain damage in neonatal bacterial meningitis.
Goat Fetuses Disconnected from the Placenta, but Reconnected to an Artificial Placenta, Display Intermittent Breathing Movements
Authors: Kozuma Shiro , Nishina Hidenori , Unno Nobuya , Kagawa Hideyuki , Kikuchi Akihiko , Fujii Tomoyuki , Baba Kazunori , Okai Takashi , Kuwabara Yoshinori , Taketani Yuji
Published: April 2003

To investigate whether placental factors are involved in the intermittent breathing movements in goat fetuses, we assessed electrocortical activity (ECoA) and tracheal pressure in 5 fetuses (124–135 days) separated from the placenta and connected for 48 h to an extrauterine fetal incubation system that provided umbilical arteriovenous extracorporeal membrane oxygenation. The fetal physiological condition on this system was almost the same as that in utero for at least 48 h after the preparation. All fetuses showed intermittent low-voltage ECoA and breathing movements. The breathing movements occurred almost exclusively during periods of low- voltage ECoA. The proportions of time spent in low-voltage ECoA and breathing movements were 48–57% and 46–56%, respectively. In conclusion, breathing movements of fetuses on the extrauterine incubation system were episodic, suggesting that intermittent breathing movements are intrinsic to fetuses, independent of placenta-derived factors.
Intracytoplasmic Sperm Injection Pregnancy with Trisomy 20p and Monosomy 22q in a Newborn Resulting from a Balanced Paternal Translocation
Authors: Belin V. , Farhat M. , Monset-Couchard M.
Published: April 2003

In infertile men who carry a balanced reciprocal translocation, intracytoplasmic sperm injection (ICSI) may induce a pregnancy with an abnormal karyotype. This report describes a previously unreported paternal reciprocal translocation leading to a chromosomally unbalanced ICSI pregnancy. The triplet pregnancy resulted in 1 normal girl, 1 physically normal boy with the same balanced paternal translocation, and a severely malformed boy with trisomy 20p and monosomy 22q who died in the neonatal period.
Functional Role of Sialic Acid in IgG Binding to Microvillus Membranes in Neonatal Rat Intestine
Authors: Gill Ravinder Kaur , Mahmood Safrun , Nagpaul Joginder Pal , Mahmood Akhtar
Published: April 2003

A close parallelism exists between sialylation and endocytotic activity of the small intestine during postnatal development in rats. Thus, the binding of 125I-labelled IgG to microvillus membranes and its relationship to membrane sialic acid has been studied in suckling rat intestine, during (a) postnatal development; (b) cortisone-induced precocious maturation, and (c) after desialylation of brush borders by neuraminidase treatment. Neuraminidase-treated membranes exhibited low (42%, p < 0.001) IgG binding. The observed decrease in IgG binding to desialylated membranes was associated with a decrease in the value of affinity constant, (–Ka = 0.4 × 106 M–1 in control and 0.23 × 106 M–1 in desialylated membranes). The number of IgG-binding sites (2.3 nmol/mg protein) was unchanged under these conditions. A similar decrease (50%) in IgG binding to brush borders was also observed in cortisone-injected pups. This was associated with reduced sialic acid (37%) content of the membranes compared to the controls. The value of –Ka was reduced from 0.4 × 106 M–1 in the control to 0.3 × 106 M–1 in the hormone-injected pups. The number of binding sites (n) was decreased from 2.2 to 1.4 nmol/mg protein under these conditions. Low concentrations of calcium (0.1–1.6 mM) in the incubation medium enhanced IgG binding (p < 0.001) to brush borders in pups but there was no change in binding of IgG to the membranes at 2 mM Ca2+ concentration compared to controls. Addition of Zn2+ or Mg2+ did not affect IgG binding under these conditions. These findings suggest a functional role of Ca2+ and sialic acid residues of the membrane glycans in IgG-receptor interactions in suckling rat intestine.
Effect of Increased Brain GABA Concentrations on Breathing in Unanesthetized Newborn Rabbits
Authors: Monin P. , Aranda J. , Bansal R. , Trippenbach T.
Published: April 2003

Evidence suggests that γ-aminobutyric acid (GABA) is involved in control of breathing and in the hypoxia-related ventilatory depression in newborns. However, this evidence is obtained mainly from studies on anesthetized animals. Because anesthesia may interfere with the GABA system, the objectives of our study were to examine effects of GABA on ventilation (VE) and ventilatory response to hypoxia and to reveal effects of repeated hypoxia on GABA concentrations in unanesthetized newborns. The study was performed in rabbits in two age groups: 1–3 days old (group I) and 10–14 days old (group II). To increase brain endogenous GABA concentrations, rabbits were injected with an inhibitor of GABA transaminase, aminooxyacetic acid (AOAA; 20 mg/kg i.p.). To prevent postmortem formation of GABA, at the end of experiments the rabbits received an inhibitor of glutamic acid decarboxylase, IP-3-mercaptopropionic acid (100 mg/kg i.p.). Animals were studied in normoxia alone, or they were exposed for 15 min to 8% O2 before and 10 and 35 min after saline or AOAA. GABA concentrations were measured in brainstem, cerebrum, and cerebellum by means of a capillary electrophoresis. In group I, AOAA had no respiratory effects. In group II, AOAA decreased VE, tidal volume, and mean inspiratory flow in normoxia and reversed VE decline during hypoxia 10 min after the injection, GABA concentrations were not age dependent and the highest in the brainstem. Repeated hypoxia increased the cerebellar GABA concentrations and had no effect in group I. These results imply that in unanesthetized rabbits, GABAergic neurotransmission in the respiratory control network becomes functional by the 2nd week of life, but it does not contribute to the biphasic ventilatory response to moderate hypoxia. In contrast, GABA-evoked block of the cerebellar inhibitory input during hypoxia may be responsible for the reversal of the VE decline in unanesthetized newborns.
Effect of Doxapram on Episodes of Apnoea, Bradycardia and Hypoxaemia in Preterm Infants
Authors: Poets Christian F. , Darraj Sandra , Bohnhorst Bettina
Published: April 2003

Aim: To study the effect of doxapram on the frequency of apnoea, bradycardia and hypoxaemia. Methods: Fifteen infants, median gestational age at birth 27 weeks (range 24–30), age at study 27 days (12–60), with ≥6 episodes of bradycardia or hypoxaemia/6 h despite serum caffeine levels in the therapeutic range, received doxapram either intravenously (0.5–2 mg/kg/h) or orally (2–8 mg/kg every 2 h). Six-hour recordings of pulse oximeter saturation (SPO2), pulse waveforms, ECG, breathing movements and nasal airflow were performed immediately before as well as 1, 3 and 6 days after onset of treatment. Recordings were analysed for apnoea (≥4 s), bradycardia (heart rate < 2/3 of baseline) and hypoxaemia (SPO2 ≤80%). Results: There was no difference between enteral and intravenous administration; results are therefore presented for the total group. Doxapram resulted in a significant decrease in the frequency of apnoea [22 (11–27) vs. 14 (7–23)/h, p < 0.01], bradycardia [3 (0–7) vs. 1 (0–3)/h, p < 0.01] and hypoxaemia [8 (0–18) vs. 2 (0– 17)/h, p < 0.01] already after 1 day of treatment, which was sustained throughout the 6-day study period. Side effects included an increase in the proportion of time spent awake [5 (0–24) vs. 12% (3–28), p < 0.01] and in gastric residuals [0% of feeding volume (0–5) vs. 4% (0–19), p < 0.05]. Enteral was switched to intravenous doxapram in 3 of 9 infants because of gastrointestinal side effects. Conclusion: Doxapram substantially reduced the frequency of apnoea, bradycardia and hypoxaemia in these patients with caffeine-resistant apnoea of prematurity. Enteral administration, however, was not tolerated in a significant proportion (33%) of infants.
Effect of Meconium Aspiration on Plasma Endothelin-1 Level and Pulmonary Hemodynamics in a Piglet Model
Authors: Kuo Chii-Yuh , Chen Ju-Yi
Published: April 2003

Sequential changes in plasma endothelin-1 (ET-1) and pulmonary hemodynamics were studied in a piglet model of meconium aspiration syndrome (MAS). Sixteen piglets were randomly divided into meconium (MEC) and normal saline (NS) groups (8 animals/group). The animals of the MEC group were instilled with meconium (20% in normal saline) via an endotracheal tube (3 ml/kg), and the animals of the NS group instilled with the same amount of normal saline. The plasma ET-1 as well as pulmonary mechanics, arterial blood gas and hemodynamics were measured at baseline and 60, 120, 180 and 240 min after instillation. The results showed that plasma ET-1 level of the MEC group was significantly higher after meconium aspiration as compared with NS group (p < 0.05 at 60 and 120 min, p < 0.01 at 180 and 240 min). Furthermore, pulmonary vascular resistance (PVR) increased and remained elevated after 120 min (p < 0.01) and pulmonary artery pressure (PAP) increased after 180 min (p < 0.01). The correlation was significant between ET-1 and PVR (r = 0.92, p < 0.001) as well as ET-1 and PAP (r = 0.89, p < 0.001). These data suggest that elevation of ET-1, which has long-lasting vasoconstriction effect, may play an important role of pulmonary hypertension of MAS.
Natural Killer Cell Activity and Delivery: Possible Influence of Cortisol and Anesthetic Agents
Authors: De Amici Donatella , Gasparoni Antonella , Chirico Gaetano , Ceriana Piero , Bartoli Antonella , Ramajoli Isabella , Moretta Antonia
Published: April 2003

The aim of this study was to evaluate the influence of the method of delivery, the level of cord blood lidocaine, and the cortisol concentration on the cord blood natural killer (NK) activity in the full-term healthy newborn. We studied healthy newborns delivered by elective cesarean section without labor under general anesthesia (n = 24), delivered by cesarean section under epidural anesthesia (n = 21), and delivered vaginally with uncomplicated labor (n = 19). The NK cell activity was significantly lower in newborns delivered by cesarean section under epidural anesthesia than it was in the general anesthesia group, while it was similar to the levels found in vaginally delivered newborns. The cortisol concentration was highest in the vaginal delivery group (589.2 ± 200 mmol/l) and lowest in the general anesthesia group (199.2 ± 81.9 mmol/l). The mean serum lidocaine concentration was 414.1 ± 370 μg/l in the epidural anesthesia group and undetectable in the other groups. In conclusion, our data suggest that the cord blood NK activity was significantly influenced by the method of delivery. This effect could be related to anesthetics given to the mother for general or epidural anesthesia or to the endocrine-metabolic variations observed after different degrees of delivery-related stress. The NK cells being a first-line defense mechanism against viral infections, the results of this study suggest an association with the occurrence of early perinatal infections, especially in preterm infants.
Morphine Metabolism in the Pregnant Guinea Pig and Her Pups
Authors: Smith Sue Ann , Woolsey Jeffrey B. , Olsen George D.
Published: April 2003

The study of chronic in utero exposure to heroin and morphine in the human is limited by polysubstance abuse. The guinea pig was used as a model for the human to determine the in vivo and in vitro effect of chronic morphine exposure on morphine metabolism in the pregnant dam and her offspring. In vivo pharmacokinetics of morphine were examined in pregnant guinea pigs following pretreatment with either saline or morphine. In vitro hepatic enzyme kinetics were also examined in a similar group of pregnant dams and their fetuses. Additional pregnant dams were allowed to give birth and their pups’ enzyme kinetics were studied at 1, 3, and 7 days. Apparent VMAX for the formation of both morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) formation was significantly increased in the morphine-treated pregnant guinea pig. However, no effect of morphine treatment was detectable on the in vivo pharmacokinetics of morphine in the pregnant dam. The apparent morphine KM for the formation of M3G was significantly different than the apparent KM for the formation of M6G. Significant age effects on the enzyme kinetics were found. The apparent VMAX for the formation of both glucuronides increased through the neonatal period. Through literature comparisons, the guinea pig was shown to have in vivo pharmacokinetics similar to the pregnant human, and the guinea pig pups were found to have enzyme development consistent with in vivo pharmacokinetic development seen in human neonates, infants and children.
Impaired Serum Lipids and Lipoproteins in Fetal Macrosomia Related to Maternal Obesity
Authors: Merzouk H. , Meghelli-Bouchenak M. , Loukidi B. , Prost J. , Belleville J.
Published: April 2003

The aim of this work was to determine lipoprotein metabolism alterations in macrosomic newborns and to see whether these lipoprotein abnormalities are parallel or not to those found in their obese or nonobese mothers. Serum lipids, apo A-I, apo B100, lipoproteins (VLDL, LDL, HDL2, and HDL3), and LCAT activity were investigated in obese and nonobese mothers and cord blood of their macrosomic or appropriate-for-gestational-age (AGA) newborns. Serum and VLDL triglyceride concentrations were higher in obese mothers of AGA newborns than in nonobese mothers. Serum triglyceride, VLDL, and apo B100 levels were higher, while serum apo A-I and HDL2 cholesterol concentrations were lower in obese mothers of macrosomic newborns than in the other groups. In their macrosomic newborns, serum lipid, lipoprotein, apo B100, and apo A-I levels were higher as compared with those of other newborns. Macrosomic newborns of nonobese mothers had lipoprotein profiles similar to those in AGA newborns. LCAT activity was similar in both mother groups and in both newborn groups. In conclusion, maternal obesity and fetal macrosomia were associated with lipoprotein abnormalities consistent with high atherogenic risk.
Missense Mutations in Norrie Disease Gene Are Not Associated with Advanced Stages of Retinopathy of Prematurity in Kuwaiti Arabs
Authors: Haider M.Z. , Devarajan L.V. , Al-Essa M. , Srivastva B.S. , Kumar H. , Azad R. , Rashwan N.
Published: April 2003

Retinopathy of prematurity (ROP) is a disease characterized by retinal neovascularization, possibly leading to retinal detachment and finally blindness. In a proportion of ROP cases, the disease progresses to advanced stages despite rigorous intervention. Missense mutations of the Norrie disease (ND) gene have been associated with progression of the disease in ROP cases from the USA. We have investigated the presence of ND gene mutations in 102 premature newborns of Kuwaiti Arab origin to replicate this finding in a different population/racial group. 56 (55%) of these newborns had normal eyes and served as controls. In 35 (34%) cases, the ROP regressed spontaneously during stage 1–3. In 11 (11%) cases, ROP progressed to advanced stages. A PCR-RFLP method was used to detect the mutations in exon 3 of the ND gene and confirmed the DNA sequence by direct sequencing of the PCR product. The [R121W] mutation of the ND gene was not detected in the premature newborns screened from our Kuwaiti population/group. For the second mutation [L108P], a genotype (PP) was present in 98% of the premature newborns screened and only in 1 of 56 normal infants was the (LL) genotype detected. Our population is genetically homogenous in that genotype (PP) was detected at codon 108 in almost all controls and ROP cases. We did not find an association between the presence or absence of missense mutations of the ND gene and the risk of severe ROP.
Contractile and Relaxing Mechanisms in Pulmonary Resistance Arteries of the Preterm Fetal Lamb
Authors: Liu Yu-An , Theis Jochen G.W. , Coceani Flavio
Published: April 2003

Isolated pulmonary resistance arteries from term fetal lambs have nitric oxide (NO)- and prostaglandin-mediated relaxing mechanisms which are activated when PO2 is raised from fetal to neonatal levels. The same vessels contract under hypoxia, and the contraction has been ascribed to endothelin-1 (ET-1). We have now studied these vasoeffector mechanisms before term (0.7 and 0.65 gestation) with the objective of determining whether their activity correlates with the development of susceptibility to oxygen changes. Experiments were carried out at neonatal PO2, when expectedly relaxing mechanisms are maximally expressed, or under hypoxia. At either fetal age, the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (100 μM), had no effect on basal tone, while indomethacin (2.8 μM) was a weak constrictor. Premature arteries did not contract when first exposed to hypoxia, but they responded marginally to a second exposure. The same arteries contracted strongly to a thromboxane A2 analogue (ONO-11113, 0.1 μM) and ET-1 (10 nM), while their contraction to activating solution (5 mM Ca2+ in K+-Krebs solution) was small and variable. At 0.7 gestation, bradykinin (0.1–100 nM), acetylcholine (0.01–10 μM), and sodium nitroprusside (0.1 nM to 10 μM) dose-dependently relaxed arteries precontracted with ONO-11113. Conversely, at 0.65 gestation the relaxation to bradykinin and acetylcholine was not dose-dependent and tended to be weaker. We conclude that preterm pulmonary arteries have viable effector mechanisms for contraction and relaxation. However, the capability for these mechanisms to be activated by PO2 changes is markedly curtailed.
Evidence for Progesterone Synthesis by Human Umbilical Cord Blood Erythrocytes
Authors: Loganath A. , Peh K.L. , Chew P.C.T. , Wong Y.C. , Ng S.C.
Published: April 2003

In order to determine whether human umbilical cord blood erythrocytes are capable of progesterone biosynthesis, sonicated preparations of plasma-free erythrocytes at the range of total cell numbers between 18.4 × 109 and 62.9 × 109 cells obtained from umbilical cord arterial and venous blood collected from normal pregnant women (n = 6, age 28–39 years) following spontaneous vaginal delivery were incubated with [7n-3H]-pregnenolone as substrate. The leucocyte content of the incubates was negligible (<0.005%). Controls (n = 4, age 29–36 years; 27.6 × 109 to 42.7 × 109 erythrocytes) obtained from cord blood of normal pregnant women were heat-denatured preparations of cells. Using the reverse-isotope dilution technique, [3H]-progesterone was isolated and characterized yielding an overall enzymic conversion which ranged between 0.27 and 0.46%. The results indicate for the first time that cord blood erythrocytes possess the 3β-hydroxysteroid dehydrogenase-5,4-en isomerase activity and are a source of progesterone in human pregnancy.
Changes in Electrocortical Brain Activity during Exchange Transfusions in Newborn Infants
Authors: Benders Manon J.L.N. , Meinesz Janneke H. , van Bel Frank , van de Bor Margot
Published: April 2003

Electrocortical brain activity (ECBA) was recorded continuously with a cerebral function monitor during 17 exchange transfusions in 13 infants (mean gestational age 36.3 ± 1.9 weeks, birth weight 2,800 ± 635 g). The minimum and maximum amplitudes, and bandwidth of the ECBA signal were determined at the end of each withdrawal and infusion period. Mean arterial blood pressure (MABP), and the minimum and maximum amplitudes decreased during the withdrawal period and increased during the infusion period. The minimum and maximum amplitude changes were very small (< 6% of baseline) and appeared to be primarily associated with MABP changes. We conclude that exchange transfusions do cause minor changes in ECBA, which are probably not clinically relevant.
Secretion of Insulin-Like Growth Factor-II into Bile of Rats of Different Ages
Authors: Philipps Anthony F. , Dvořák Bohuslav , Anderson Gary G. , Grille James G. , Williams Catherine S. , Koldovský Otakar
Published: April 2003

Bile from rats of different ages (suckling 10–12 days; weanling 30–33 days, and adult 60–70 days) was collected and studied for the presence of immuno- and receptor-assayable insulin-like growth factor-II (IGF-II) concentrations. Concentrations of RIA IGF-II in bile were highest in suckling rats (230 ± 38 ng/ml) and lowest in adults (47 ± 7 ng/ml). These concentrations were approximately twice those of the bile IGF-I concentration in sucklings, as measured in a previous study. Selected bile samples were also assayed using a competitive binding assay with a crude preparation of adult rat liver membranes bearing the IGF-II receptor. These studies confirmed the presence of receptor- (as well as immuno-) active IGF-II in bile. Since bile flow rates increased dramatically after the suckling period, bile delivery rates of IGF-II were normalized as picograms per gram body weight per hour. When such calculations were done, bile IGF-II delivery rates to the small intestine were highest in sucklings and weanlings in comparison to adult rats. Thus non-enterically derived (milk- and bile-borne) IGF-II delivery to the suckling small intestine can be approximated at roughly 1 μg/day. Unlike IGF-I, intravenously injected IGF-II could not be detected in suckling bile, suggesting a predominantly hepatic origin. From this study we conclude that there exists a significant delivery of receptor-active IGF-II to the gastrointestinal tract of rats of all ages.
Catch-Up Growth in 166 Small-for- Gestational Age Premature Infants Weighing Less than 1,000 g at Birth
Authors: Monset-Couchard M. , de Bethmann O.
Published: April 2003

Catch-up growth was studied in 166 children born with an extremely low birth weight (<1,000 g) and small-for-gestational age (SGA, <10th percentile birth weight for gestational age). Of these children 159 were followed up for between 4 and 18 years (median 9 years). Group A, SGA <10th percentile of Lubchenco curves only; group B, <10th percentile of Mamelle’s curves but >5th percentile, and group C, <5th percentile of Mammelle’s curves. Catch-up growth was considered to be achieved when height, weight, and head circumference (HC) reached –2 SD of French reference data and remained above this limit afterwards. Catch-up growth in height was achieved in 126/156 children or 81% (group A 88%; group B 84%; group C 74%), before 3 years of age in 100/127 (78%). Seven children below –2 SD received growth hormone (1 child who caught up was excluded from the results). Catch-up growth in weight was achieved in 126/159 children or 79% (group A 86%; group B 82%; group C 73%), before 3 years of age in 87/126 (69%). Catch-up growth in HC was achieved in 126/156 or 81% (group A 78%; group B 92%; group C 77%), before 3 years of age in 102/127 (80%). Overall catch-up growth was achieved for all three parameters in 65% of children, two of three parameters in 19%, and one of three parameters in 8%. Eleven children never caught up on any parameter. While weight is a lesser concern and HC is not liable to intervention, a greater number of short children might benefit from growth hormone therapy.
High-Dose Inhaled Nitric Oxide and Hyperoxia Increases Lung Collagen Accumulation in Piglets
Authors: Ekekezie Ikechukwu I. , Thibeault Donald W. , Rezaeikhaligh Mohammad H. , Mabry Sherry M. , Norberg Michael , Reddy G. Kesava , Youssef Jihan , Truog William E.
Published: April 2003

Nitric oxide (NO), a pro-oxidant gas, is used with hyperoxia (O2) to treat neonatal pulmonary hypertension and recently bronchopulmonary dysplasia, but great concerns remain regarding NO’s potential toxicity. Based on reports that exposure to oxidant gases results in pulmonary extracellular matrix injury associated with elevated lavage fluid levels of extracellular matrix components, we hypothesized that inhaled NO with or without hyperoxia will have the same effect. We measured alveolar septal width, lung collagen content, lavage fluid hydroxyproline, hyaluronan and laminin levels in neonatal piglets after 5 days’ exposure to room air (RA), RA + 50 ppm NO (RA + NO), O2 (FiO2 > 0.96) or O2 + NO. Matrix metalloproteinase (MMP) activity and MMP-2 mRNA were also measured. In recovery experiments, we measured lung collagen content in piglets exposed to RA + NO or O2 + NO and then allowed to recover for 3 days. The results show that lung collagen increased 4-fold in the RA + NO piglets, the O2 and O2 + NO groups had only a 2-fold elevation relative to RA controls. Unlike the RA + NO piglets, the O2 and O2 + NO groups had more than 20-fold elevation in lung lavage fluid hydroxyproline compared to the RA group. O2 and O2 + NO also had increased lung MMP activity, extravascular water, and lavage fluid proteins. MMP-2 mRNA levels were unchanged. After 3 days’ recovery in room air, the RA + NO groups’ lung collagen had declined from 4-fold to 2-fold above the RA group values. The O2 + NO group did not decline. Alveolar septal width increased significantly only in the O2 and O2 + NO groups. We conclude that 5 days’ exposure to NO does not result in pulmonary matrix degradation but instead significantly increases lung collagen content. This effect appears potentially reversible. In contrast, hyperoxia exposure with or without NO results in pulmonary matrix degradation and increased lung collagen content. The observation that NO increased lung collagen content represents a new finding and suggests NO could potentially induce pulmonary fibrosis.
Effect of Polyclonal Anti-TNFα Antibody on Endotoxic Shock in Suckling Rats
Authors: Bhola Monika , Goto Masakatsu , Chen Hui Y. , Myers Thomas F.
Published: April 2003

The aim of this study was to evaluate the effect of anti-tumor necrosis factor α (TNFα) antibodies on the TNFα gene expression in a neonatal septic shock model. Ten-day-old Sprague-Dawley rats were divided into four groups and given intraperitoneal (ip) injection as follows: group 1: 0.1 ml saline; group 2: 0.1 mg/kg Salmonella enteritidis lipopolysaccharide (LPS); group 3: 1 mg/kg of anti-TNFα antibodies (Ab); group 4: 0.1 mg/kg of LPS and 1 mg/kg of Ab. We found that in group 2, LPS induced shock, demonstrating hypoglycemia and lactacidemia (p < 0.05) and death (81.8%). Ab decreased the mortality significantly (35%) and attenuated the hypoglycemia (35 ± 8 mg/dl in group 2 vs. 53 ± 3 mg/dl in group 4) and lactacidemia (5.40 ± 0.63 vs. 2.35 ± 0.45 mmol) at 8 h in group 4 when compared to group 2. Northern blot demonstrated a significant decrease in TNFα mRNA expression in group 4 as compared to group 2, at 2 h after LPS injection. We conclude that the beneficial effects of anti-TNFα antibodies on LPS-induced shock may be due to decreased TNFα gene expression.
Blood Pressure Control and Hemodynamic Changes in Patients on Long Time Dialysis Treatment
Authors: Luik Antinus J. , Charra Bernard , Katzarski Krassimir , Habets Jos , Cheriex Emile C. , Menheere Paul P.C.A. , Laurent Guy , Bergström Jonas , Leunissen Karel M.L.
Published: April 2003

In dialysis patients blood pressure can be well controlled with long dialysis (3 times a week for 8 h) in contrast to a more common short dialysis regime (3 times a week for 4 h). We studied whether the good blood pressure control in patients on long dialysis as compared to patients on short dialysis was associated with a decrease in extracellular fluid volume. Two-day interdialytic ambulatory blood pressure monitoring was performed in 26 non-diabetic patients on long dialysis, in 22 patients on short dialysis, matched for the years they were on dialysis treatment, and during 24 h in 19 healthy volunteers. After full equilibration, 24 h after dialysis, echography of the inferior caval vein was performed to determine fluid state. Cardiac dimensions and stroke index were measured by echocardiography. A blood sample was drawn for the determination of electrolytes and vasoactive hormones. 73% of the patients on short dialysis were using antihypertensive medication in contrast to none of the patients on long dialysis. However, blood pressure was significantly lower in patients on long dialysis (115 ± 21/67 ± 11 mm Hg) when compared to patients on short dialysis (143 ± 26/81 ± 16 mm Hg). Indexed caval vein diameter, left ventricular diameter index, and atrial natriuretic peptide were not significantly different in patients on long dialysis compared to patients on short dialysis. Also the cardiac index was comparable in patients on long and short dialysis. However, the total peripheral resistance index was significantly lower in patients on long dialysis compared to the patients on short dialysis and normal controls. The left ventricular mass index was increased in both patients on long and short dialysis compared to controls. We conclude that patients on long dialysis have adequate blood pressure control that seems mainly to be caused by a low total peripheral resistance. These data also suggest that factors other than a lower fluid state contribute to the good blood pressure control in patients on long dialysis.