bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal and Choroidal Blood Flow Response to Hyperoxemia after Severe Hypoxemia in the Newborn Piglet
Authors: Odden Jan-Petter , Rootwelt Terje , Stiris Tom , Hall Christian , Bratlid Dag
Published: October 2009

To investigate the effect of hyperoxemia on the ocular circulation after a severe hypoxemic insult (8% O2 until base excess reached ––20 mmol/l), we randomly reoxygenated newborn piglets with 100% (study group, n = 8) or 21% O2 (control group, n = 10). Retinal (RBF) and choroidal blood flow (ChBF) were measured with radioactive microspheres. The hypoxemic insult did not change RBF, while ChBF significantly decreased. However, a marked reduction in both retinal (RDO2) and choroidal oxygen delivery (ChDO2) was observed, probably resulting in hypoxia both in the inner and outer retina. At 5 and 20 min of reoxygenation a similar hyperemic response in the retina was seen in both groups. RDO2 also increased significantly and no significant differences between the 2 groups could be demonstrated. We found no indication of retinal vasoconstriction during hyperoxemia. We speculate that the vasodilating effect of the preceding hypoxemia overrules the vasoconstrictive effect of the retinal vessels normally found during hyperoxemia.
Effect of L-Arginine Infusion on Infants with Persistent Pulmonary Hypertension of the Newborn
Authors: McCaffrey Martin J. , Bose Carl L. , Reite Pamela D. , Stiles Alan D.
Published: October 2009

Nitric oxide (NO) is thought to be a primary mediator of the reduction in pulmonary vascular resistance which occurs in the newborn period. L-arginine is the precursor for the formation of nitric oxide in the pulmonary endothelium. Low serum arginine levels have been reported in infants with persistent pulmonary hypertension of the newborn (PPHN). We infused a single L-arginine dose of 500 mg/kg over 30 min to 5 consecutive infants with PPHN. Ninety minutes after infusion we observed an associated rise in PaO2 of 37 to 84 mm Hg and, in 4 of 5 infants, a reduction in oxygenation index (OI) of 33–50% over the 5-hour period following infusion. Infusion was not associated with adverse effects. These observations suggest that L-arginine administration may be an effective therapeutic alternative in infants with PPHN.
Scanning Gel Densitometry of Amniotic Fluid Acetylcholinesterase and Butyrylcholinesterase: Quantification of ‘Faint-Positive’ Bands in Fetal Malformations
Authors: Dupont Madeleine , Vallet Bernard , Brun Annie , Boulot Pierre , Demaille Jacques
Published: October 2009

The quantification of ‘faint-positive’ cholinesterases in amniotic fluid was performed in 40 patients with positive acetylcholinesterase (AchE) tests. Fetuses with anencephaly and open spina bifida presented an AchE/butyrylcholinesterase (A/B) ratio of more than 0.3 with clearly dense bands. Fetuses with gastroschisis showed a ‘faint-positive’ AchE band (A/B < 0.3). In 5 fetuses (1 teratoma, 3 open spina bifida, 1 unaffected) we found faint AchE and butyrylcholinesterase bands.
Activities of Trypsin and Lipase in Duodenal Aspirates of Healthy Preterm Infants: Effects of Gestational and Postnatal Age
Authors: Boehm G. , Bierbach U. , DelSanto A. , Moro G. , Minoli I.
Published: October 2009

Lipase and trypsin activities were estimated in preprandially aspirated duodenal juice of preterm infants with gestational ages between 29 and 32 weeks (group I, n = 33) or between 33 and 36 weeks (group II, n = 22) during the first 6 weeks of postnatal life. The results were compared with the enzyme activities measured in 2- to 6-year-old children. There were no significant differences of the mean lipase or trypsin activities between the two groups (lipase; group I 13.7 ± 7.9, group II 15.9 ± 9.8 U/ml; trypsin: group I.7.9 ± 4.7, group II 8.5 ± 5.1 U/ml). The activities of both enzymes increased significantly and similarly in both groups with postnatal age (lipase: group I r = 0.732, p < 0.01, group II r = 0.743, p < 0.01; trypsin: group I r = 0.705, p < 0.01, group II r = 0.669, p < 0.01). At the end of the study the lipase activities of both groups reached approximately 35% of the values found in the older children, whereas the trypsin activities reached the reference values within the 1st month of life. The results indicate an asynchronously age-related development of lipase and trypsin. The development of the lipase activity is delayed in comparison to the trypsin activity which should be considered in the nutritional management of preterm infants.
Effect of Retinoids on Fetal Lung Development in the Rat
Authors: Masuyama Hisashi , Hiramatsu Yuji , Kudo Takafumi
Published: October 2009

We investigated the effect of retinoids on fetal lung development in the rat. The concentration of retinyl palmitate increased rapidly to a peak on day 17 of gestation and decreased to a minimum on day 21 of gestation; there was a slight increase after birth. Retinoid acid receptor (RAR)-α and -β mRNA were detected in all samples obtained from perinatal and adult rat lung, and only a trace of RAR-γ mRNA was detected in the fetuses on days 15, 17 and 19 of gestation and in the adults by reverse transcriptase-polymerase chain reaction. After a maternal retinol deficiency of 28 days’ duration, fetal body and lung weights were significantly lower than those of controls; the concentrations of retinyl palmitate and phosphatidylcholine (PC) in the lung after a maternal retinol deficiency of 14,21 or 28 days were significantly lower than those of controls. Expression of RAR-β mRNA in the group with 28-day retinol deficiency was lower than in controls, that of RAR-α mRNA was increased and that of RAR-γ mRNA was not influenced by retinol deficiency. The rate of choline incorporation into PC in fetal lung explants was significantly higher in the group treated with retinoic acid (RA) than in controls. RA enhanced the effect of epidermal growth factor on choline incorporation and prevented that of dexamethasone. In conclusion, storage of retinoids occurs and all three types of RAR mRNA are expressed during fetal lung growth and development, and as retinoids exert both a direct and an indirect effect on choline incoporation in fetal rat lung, we think that they may be one of the factors controlling fetal lung development in this species.
Ontogeny of Dopamine Daily Rhythms within Rabbit Brainstem Regions
Authors: Gingras Jeannine L. , Lawson E.E. , McNamara M.C.
Published: October 2009

To examine the development of daily variations in dopamine levels, we measured dopamine concentrations within five distinct brainstem regions in 3- and 21-day-old, and adult rabbits at 09.30, 15.30, 21.30 and 03.30 h. Dopamine was measured by radioenzymatic assay and the dopamine concentration was expressed relative to wet tissue weight. In addition to defining the presence of a daily variation in the dopamine concentration in the whole brainstem, we were interested in identifying brainstem region-specific differences in this daily variation. Our data suggest that daily variations in dopamine concentrations are established by 3 days of life. Analysis of gross brainstem daily variation data suggest a peak in the dopamine concentration during the early light phase (09.30 h) for 3-day-old animals in contrast to a late light phase peak (15.30 h) for 21-day-old animals. Adult animals showed a peak in the early dark phase (21.30 h). These gross daily variations reflect the net sum of distinct region-specific patterns in the dopamine concentration. Analysis by region reflects a region-specific ontogeny in the development of daily variations for dopamine. Dopamine is involved in cardiorespiratory regulation. The observed developmental patterns may relate to the maturation and integration of these physiologic processes.
Main Routes of Plasma Lactate Carbon Disposal in the Midgestation Fetal Lamb
Authors: Carter Brian S. , Moores, Jr. Russell R. , Teng Cecilia , Meschia Giacomo , Battaglia Frederick C.
Published: October 2009

The turnover rates of plasma lactate, normalized for O2 consumption rate, are higher in the fetus than in the adult. This occurs despite very low rates of fetal gluconeogenesis which preclude the recycling of lactate carbon into glucose. In an effort to establish the main routes of disposal of fetal plasma lactate, 12 midgestation ovine fetuses (age 74 ± 1 days) were infused intravenously at constant rate with L-[U-14C]lactate for a 4-hour period. At the end of the infusion, the amounts of 14C retained by the fetus and by the placenta, and the distribution of the retained 14C in free and protein-bound amino acids and in lipids were measured. Of the total 14C infused, 17.0 ± 1.4% was recovered in the placenta, 4.0 ± 0.3% in the fetal liver, and 15.0 ± 0.8% in the extrahepatic fetal tissues. Of the retained radioactive carbon, 45-57% was recovered in the free and protein-bound amino acid fractions and 11-17% in the lipid fractions. Approximately 90% of the 14C in the free amino acid fractions was present as glutamate/glutamine, serine, glycine, and alanine carbon. In conjunction with data on fetal CO2 production from lactate carbon, these results demonstrate that the main routes of fetal lactate disposal are oxidation and synthesis of nonessential amino acids and lipids.
Cooperation between Transcription Factors Regulates Liver Development
Authors: Aran Adi , Cassuto Hanoch , Reshef Lea
Published: October 2009

Characterization and cloning of liver-enriched transcription factors have provided the tools to study the regulation of liver differentiation. Characterization of the temporal and spatial expression of these factors have shown a sequential order of appearance, in coordination with the expression of their target genes, during liver development. Evidence has accumulated showing cooperation between distinct factors in regulating liver-specific gene expression. Since each of these factors is not uniquely expressed in the liver, yet, the liver is the only tissue that expresses all of these factors, the cooperation between the coexisting liver-enriched factors could constitute the basis for the regulation of liver-specific gene expression.
Overview of Clinical Trials Comparing Natural and Synthetic Surfactants
Authors: Halliday Henry L.
Published: October 2009

This overview summarizes the ten randomized clinical trials that have compared different surfactant preparations. Six trials, enrolling 2,450 babies with respiratory distress syndrome (RDS), compared Survanta and Exosurf. Babies treated with the natural surfactant had lower oxygen requirements for at least 3 days than those treated with the synthetic surfactant. The babies treated with Survanta had lower risks of neonatal mortality (odds ratio, OR, 0.80; 95% confidence interal, CI, 0.65–1.00), retinopathy of prematurity (OR 0.68; 95 % CI 0.50–0.94), and death or bronchopulmonary dysplasia (OR 0.84; 95% CI 0.70–1.00) when compared to those treated with Exosurf. Infasurf has been compared with Exosurf in two studies: one as prophylaxis and the other a rescue trial. Similar, although non-significant benefits were found for the natural surfactant. When all eight trials were included in a meta analysis, there was a significant reduction in the odds of pulmonary air leaks (OR 0.52; 95% CI 0.41–0.66) for babies treated with natural as compared with synthetic surfactants. For seven trials (3,576 babies) comparing natural and synthetic surfactants to treat RDS (six comparing Survanta and Exosurf and one Infasurf and Exosurf), there was a significantly reduced risk of neonatal mortality (OR 0.80; 95% CI 0.66–0.97) with natural as compared with synthetic surfactant treatment. In two further trials different natural surfactant preparations have been compared. Reduced oxygen needs for 24 h after treatment were found for Infasurf and Curosurf, respectively, when compared to Survanta. Apparent longer-term benefits from these surfactants were not statistically significant. Further trials are needed to be certain of the differences between various surfactant preparations.
The Surface-Associated Surfactant Reservoir in the Alveolar Lining
Authors: Schürch Samuel , Qanbar Riad , Bachofen Hans , Possmayer Fred
Published: October 2009

A small atmospheric bubble was introduced into a surfactant suspension in a captive bubble surfactometer. After film formation to the equilibrium surface tension at the bubble air-liquid interface, the bulk phase surfactant was depleted by replacing the chamber contents several times with a saline-CaCl2 solution. The remaining film adsorbed at the bubble surface was then compressed stepwise in quasi-static fashion to near zero minimum surface tension. This was followed by a series of quasi-static expansion steps to surface tensions slightly above equilibrium. The surface tension of films from lipid extract surfactants and phospholipid mixtures did not increase in a manner consistent with the presence of a single surface monolayer. After the initial, rapid rise in surface tension at each expansion step, a decrease in surface tension to a new value was observed. This decrease in surface tension is likely due to the adsorption of ‘surplus’ material from a Ê»surface-associated reservoir’ into the surface active film. The presence of surplus non-monolayer surfactant material in situ at the alveolar surface was also demonstrated by electron microscopy. SP-A acted as a potent promoter for the movement of excess material (equivalent to 2-3 monolayers) at the interface into the surface active film. In contrast, inhibitory serum proteins prevented the formation of a surface-associated reservoir or the adsorption of excess material into a surface active film.
Ascorbic Acid Concentrations in Umbilical Cord Veins and Arteries of Preterm and Term Newborns
Authors: Guajardo Leonel , Beharrys Kay D.A. , Modanlou Houchang D. , Aranda Jacob V.
Published: October 2009

Ascorbic acid (AA) is a powerful antioxidant required for the defense against oxidative stress. At present it is not known whether AA may play a role in the developmental process of the fetus. We therefore determined the relationship of AA levels between the umbilical cord vein (UCV) and umbilical cord artery (UCA) of preterm (< 37 weeks of gestation) and term (> 37 weeks of gestation) infants and compared those levels to matched maternal venous AA levels. We also assessed the association between UCV plasma AA levels with birth weight and gestational age by measuring AA in 88 UCV plasma samples and 58 UCA plasma samples obtained from newborn infants ranging in gestational age from 24 to 42 weeks and birth weight from 675 to 5,020 g, by high pressure liquid chromatography. Maternal venous samples were collected at the time of delivery. The mean UCV plasma AA levels (mg/dl) were significantly lower in the preterm group than in the term group (0.43 ± 0.59 and 1.16 ± 0.97, respectively; p < 0.002); however, the mean UCA plasma AA levels did not differ between the groups. In contrast, mean maternal venous plasma AA levels of the preterm group (1.33 ± 0.62) were significantly higher than those of the mothers in the term group (0.72 ± 0.69; p < 0.01). A direct correlation was found between UCV levels and birth weight (r = 0.23, p < 0.05), and UCV levels and gestational age (r = 0.23, p < 0.05). We speculate that the preterm gestation, AA may be transported across the placenta in its oxidized form (dehydroascorbic acid) to the fetus, where it is then reduced to AA. The underlying mechanism(s) involved in this process and the clinical significance of these findings need to be elucidated.
Maternal and Neonatal Plasma Transthyretin (Prealbumin) Concentrations and Birth Weight of Newborn Infants
Authors: Jain Sushil K. , Shah Mortal , Ransonet Leigh , Wise Rodney , Bocchini, Jr. Joseph A.
Published: October 2009

Animal studies have shown that maternal protein deficiency during pregnancy affects fetal birth weight. This study has examined whether or not the fetal birth weight of full-term newborns has any relationship with the acute protein nutrition status of the mother. Protein nutrition status was assessed by measuring the plasma transthyretin (prealbumin) concentrations. Plasma transthyretin concentrations (mean ± SE) from the cord blood of 20 newborns (10.9 ± 0.5 mg/dl) were significantly lower (p < 0.000000001) compared with respective maternal concentrations (17.8 ± 0.8). There was a significant correlation of transthyretin concentrations between mothers and newborns (r = 0.61, p < 0.005), and of newborn birth weight with plasma transthyretin concentrations of newborns (r = 0.57, p < 0.01) and mothers (r = 0.51, p < 0.03). This study documents a relationship of fetal birth weight with maternal and newborn plasma transthyretin concentrations.
Effects of Methamphetamine on Rat Embryos Cultured in vitro
Authors: Yamamoto Yoshiko , Yamamoto Keiichi , Abiru Hitoshi , Fukui Yuko , Shiota Kohei
Published: October 2009

Wistar rat embryos were explanted on day 10.5 of gestation and exposed in vitro to methamphetamine (MAMP)at a concentration of 0.1 0.2,0.4,0.6, or 0.8 mM for 24 h, and the direct teratogenic effects of the drug on rat embryos were examined. The viability of cultured embryos was not affected by the MAMP treatment. The yolk sac diameter was reduced at MAMP concentrations of 0.6 and 0.8 mM. The crown-rump length and the somite number of the embryos decreased significantly and dependently on the MAMP concentrations at 0.4-0.8 mM. The protein content was also significantly reduced at 0.4-0.8 mM. The developmental score was decreased in a concentration-dependent manner. The frequency of malformed embryos significantly increased at 0.6 and 0.8 mM. The malformations induced in treated embryos included microcephaly, neural tube defects, incomplete rotation of the body axis, and tortuous spinal cord. Abnormal histological changes such as derangement and necrosis in the neuroepithelial tissue were observed in embryos exposed to high concentrations of the drug. Our results revealed the direct embryotoxic and teratogenic effects of MAMP in the rat.
Effects of Porcine Growth Hormone on Pregnancy and Fetal/Neonatal Development in the Rat
Authors: Spence Stan , Mattson Britta , Vetter Christine , Cukierski Mark , Prahalada Srinivasa
Published: October 2009

Porcine growth hormone was given subcutaneously twice daily to two groups of 20 females at dose levels of 0.5 and 2.5 IU/kg (1 and 5 IU/kg/day). A control group of 20 females was similarly treated with vehicle. The females were given either vehicle or porcine growth hormone from gestation day (GD) 6 through GD 21, for 10 females that were cesarean sectioned, or through lactation day (LD) 21, for 10 females scheduled for natural delivery. There were no deaths, abortions, or drug-related physical signs in any treatment group. Drug-related effects during gestation were limited to significant (p < 0.05) pharmacologically mediated increases in Fo maternal body weight gain during GD 6-20 in the 2.5-IU/kg group, approximately 24% above controls. During LD 0-21, there were significant (p < 0.05) dose-related increases in average maternal body weight gain in the 0.5- and 2.5-IU/kg groups (72 and 200% above controls, respectively). Consistent with these findings, there were dose-dependent increases in maternal serum growth hormone and IGF-1 levels noted on GD 21 and LD 21 in both drug-treated groups. There were no drug-related effects on embryonal/fetal survival, GD 21 fetal body weight, placental weight, fetal femur length and width, or fetal morphology as determined by external, visceral, and skeletal examinations. There were no drug-related effects on Fi pup mortality, physical signs, body weight, biparietal diameter, liver weight, and femur length or width. These data suggest that subcutaneous administration of growth hormone to pregnant and lactating rats, at a dose that produces significant (p < 0.05) increases in maternal body weight gain and serum IGF-1 levels, has no apparent effect on embryonal/fetal development or preweaning growth.
The Piglet as a Model for Cerebral Circulation: An Angiographic Study
Authors: Haaland Kirsti , Orderud Wenche Jenny , Thoresen Marianne
Published: October 2009

The aim of this study was to further investigate the possibilities and limitations of the newborn piglet as a model for neonatal cerebral circulation and injury. The precerebral and cerebral circulation was visualized by aortic arch contrast injection and selective injections into internal carotid and vertebral arteries. Due to the well-developed collateral circulation, it is not possible to produce severe focal cerebral ischemia in the piglet by ligation of extracranial arteries. It is possible to produce a modified common carotid artery which supplies mainly intracerebral tissues and is accessible for continuous measurements of cerebral blood flow.
Gastroesophageal Reflux and Acute Life-Threatening Episodes: Role of a Central Respiratory Depression
Authors: Beyaert Christian , Marchal François , Dousset Brigitte , Serres Marie-Armelle , Monin Pierre
Published: October 2009

The aim of this study was to evaluate plasma levels of β-endorphins in babies with gastroesophageal reflux (GOR) admitted for acute life-threatening episodes (ALTE). In case of ALTE (n = 15), β-endorphin levels were significantly increased compared to sudden infant death syndrome siblings with GOR of a similar gravity evaluated for risk factors (n = 13). β-Endorphin levels are decreased following successful treatment of GOR. Studies of ventilation suggest that changes in the central respiratory drive are associated with a reduction in plasma β-endorphin levels.
Relationship between Serum Unconjugated Bilirubin Levels and the Autofluorescence of White Blood Cells in Neonatal Jaundice
Authors: Özkan Hasan , Akkoç Nurullah , Aydın Adem , Kavukçu Salih , Olgun Nur , Irken Gülersu , Akyol Faize , Çevik Necla T.
Published: October 2009

In this study, using flow cytometry, we investigated the autofluorescence emitted by lymphocytes, monocytes and neutrophils exposed to different unconjugated bilirubin concentrations and investigated the relationship between these parameters. Different unconjugated bilirubin concentrations were prepared from a newborn serum with an unconjugated bilirubin concentration of 800 µmol/l. The same concentrations of unconjugated bilirubin have been prepared from pure bilirubin. 10 µl of cord blood were incubated at room temperature for 15 min with 90-µl solutions with different bilirubin concentrations prepared from both serum and pure bilirubin. After incubation, cells were washed three times with PBS, erythrocytes were lysed by lysing buffer and run through flow cytometry immediately. Autofluorescence was measured by recording mean fluorescence channels for lymphocytes, monocytes and neutrophils. There was a good correlation between serum concentrations of unconjugated bilirubin that cells were exposed to and the autofluorescence intensity of neutrophils (r = 0.904, p < 0.005), monocytes (r = 0.759, p < 0.05) and lymphocytes (r = 0.766, p < 0.01). Results obtained with pure bilirubin were also similar. Autofluorescence emitted by lymphocytes was lower than that of monocytes (p < 0.01) or neutrophils (p < 0.0005).
Gene Expression of Fatty Acid Synthesizing Enzymes in Fetal Rat Lung in Prolonged Pregnancy
Authors: Walther Frans J. , Batenburg Joseph J.
Published: October 2009

In fetal rat lung the amounts of mRNAs encoding fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACL) increase in late gestation and drop around birth. To study the mechanism of the perinatal decrease, pregnancy was prolonged from 22 (term) to 25 days in rats with daily injections of progesterone. Progesterone did not affect the levels of lipogenic enzyme mRNAs in fetal lung prior to term, but significantly delayed the perinatal decrease in the levels of lung FAS and ACC mRNA. Although for ACL mRNA abundance the differences were not statistically significant, its patterns in the control and progesterone groups were similar to those of FAS and ACC mRNA. Malic enzyme mRNA did not change between 20 and 25 days after conception in either group. These results suggest that the decrease in FAS and ACC mRNA at term can be partially explained by labor, delivery, air-breathing or switch from carbohydrate to fat metabolism.
Effects of Calcitriol on Proliferation and Differentiation of Human Fetal Jejunum
Authors: Ménard Daniel , Levy Emile , Delvin Edgard E.
Published: October 2009

Several lines of evidence suggest a role for calcitriol in the regulatory mechanisms of intestinal development. Using organ culture as a model, we have verified whether this hormone influenced the cellular proliferation and differentiation processes of the developing human jejunum. We show that calcitriol supports a proliferative process in the fetal human jejunum at 11 weeks of gestation and a differentiating activity in samples obtained between 16 and 20 weeks. The present data therefore suggest that calcitriol has a biphasic effect on the development of the human intestinal epithelium and warrants caution in extrapolating to human, data observed in developing rodents and human carcinoma cell lines.
Alveolar-to-Vascular Leakage of Surfactant Protein A in Ventilated Immature Newborn Rabbits
Authors: Robertson Bengt , Curstedt Tore , Herting Egbert , Sun Bo , Akino Toyoaki , Schäfer Klaus P.
Published: October 2009

We measured alveolar-to-vascular leakage of surfactant protein A (SP-A) in immature newborn rabbits delivered at a gestational age of 27 days. Experimental animals received, via a tracheal cannula, 2 ml/kg of a mixture of modified porcine surfactant (Curosurf, 80 mg/ml) and human recombinant SP-A (4 mg/ml). Littermate controls received the same volume of human SP-A in saline (4 mg/ml). After 30 min of artificial ventilation with a frequency of 40/min and an inspiration time of either 0.75 or 0.45 s, blood was sampled from the right ventricle and the lungs were lavaged. The content of human SP-A in serum and lung lavage fluid was determined with ELISA kits, and the alveolar-to-vascular leak expressed as the quotient of total SP-A in serum and lavage fluid. The leak in control animals amounted to about 2% of SP-A in lung wash and was several times higher in these animals than in those receiving surfactant. The leak was of the same order irrespective of whether the animals were ventilated with long or short inspiration time. We speculate that serum levels of SP-A may reflect the degree of lung injury in various forms of respiratory failure.
Role of Nitric Oxide in the Regulation of the Cerebral Circulation in the Lamb Fetus during Normoxemia and Hypoxemia
Authors: van Bel Frank , Sola Augusto , Roman Christine , Rudolph Abraham M.
Published: October 2009

The influence of nitric oxide (NO) blockade on resting tone and on hypoxia-induced vasodilatation of the cerebral vascular bed was examined in chronically instrumented lamb fetuses. Total (Qbrain-tot) and regional brain blood flow were measured using radioactive microspheres. NO blockade was achieved by Nω-nitro-L-arginine (NNLA) infusion into the carotid artery via a lingual artery. Fetal cerebral blood flow and cerebral vascular resistance (Rcer) were determined during normoxemia and hypoxemia and before and during infusion of L-arginine. During normoxemia, the brain blood flow decreased, and the resistance increased significantly after NNLA infusion (Qbrain-tot from 129 ± 25 to 89 ± 26 ml/100 g/ min, p < 0.05; Rcer from 0.46 ± 0.03 to 0.80 ± 0.09 mm Hg/ ml/100g/min, p < 0.05). During hypoxemia before NNLA infusion, Qbrain-tot increased (from 129 ± 25 to 187 ± 56 ml/100 g/min, p < 0.05), and Rcer decreased (from 0.46 ± 0.03 to 0.39 ± 0.07 mm Hg/ml/l00 g/min, p < 0.05). This vasodilatory response was largely blocked after NNLA (Q 143 ± 45 ml/100 g/min; Rcer 0.58 ± 0.07 mm Hg/ml/100 g/min). The response to hypoxemia was restored after infusion of L-arginine (Qbrain-tot 180 ± 47 ml/100 g/min). The resting tone of the cerebral vascular bed of the lamb fetus is under NO control, and NO mediates the cerebral vasodilatory response to hypoxia in the lamb fetus.
Influence of Postnatally Administered Glucocorticoids on Rat Lung Growth
Authors: Tschanz S.A. , Damke B.M. , Burri P.H.
Published: October 2009

Postnatal formation of alveoli can be largely prevented by glucocorticoid treatment, which accelerates alveolar wall thinning and inhibits outgrowth of new interalveolar septa. Since a double capillary network is a prerequisite for interalveolar wall formation, we hypothesized that glucocorticoid treatment inhibited alveolar formation, indirectly, by inducing precocious microvascular maturation. Between 4 and 60 days we followed up qualitatively and quantitatively the effects of 2 weeks (days 2–15) of daily Decadron® (Dexamethasone phosphate) injections on the lung structure. Glucocorticoid induced only small changes in body weight or lung volume. However, during the first 2 weeks, it accelerated alveolar wall thinning and microvascular maturation and partly suppressed the outgrowth of new interalveolar septa. In Decadron-treated rats, the interstitial tissue mass was significantly reduced during the first 2 weeks, and a larger alveolar surface area was endowed with a capillary monolayer on days 10 and 13. One week after drug withdrawal, the trend towards precocious maturation of the lung was reversed. Lipofibroblasts reappeared, and inter-airspace septa regressed towards a more immature state. We found indications of a second burst of alveolization by resumption of secondary septa formation. The late sequelae of Decadron treatment (day 60) were manifested as an ‘emphysematous’ condition of the lungs, with larger and fewer airspaces, the delayed alveolization being insufficient to compensate for the initial deficit.
Pulmonary Effects after Surfactant Treatment in Premature Infants with Severe Respiratory Distress Syndrome
Authors: Farstad Teresa , Bratlid Dag
Published: October 2009

To understand the mechanisms behind the improved oxygenation after intratracheal surfactant instillation, the immediate effects on lung volume and pulmonary mechanics were analyzed. All infants studied were enrolled in multicenter trials in which surfactant therapy was instituted according to a rescue protocol. Infants received either synthetic surfactant (Exosurf) or modified porcine surfactant (Curosurf). Measurements of lung volume and pulmonary mechanics were successfully performed in 12 patients with a birth weight of 1.3 ± (SD) 0.6 (range 0.7-2.7) kg, and a gestational age of 28.3 ± (SD) 1.4 weeks. Functional residual capacity (FRC) and pulmonary mechanics were measured during mechanical ventilation. The FRC increased significantly by 70% (median), from 7.10 ± (SD) 2.8 ml/kg to 11.5 ± 3.3 ml/kg after surfactant instillation. However, a concomitant decrease in specific compliance was also seen. These findings could suggest that this immediate increase in FRC is initially nonuniform. However, since no significant correlation between changes in FRC and improvement in arterial-to-alveolar oxygen tension ratio is seen, other effects of surfactant must also be considered. These could include local and/or systemic changes in hemodynamics, such as decreased shunting as well as various effects on gas diffusion.
CD26 and CD31 Surface Antigen Expression on Human Colostral T Cells
Authors: Bertotto A. , Spinozzi F. , Gerli R. , Castellucci G. , Bassotti G. , Crupi S. , Fabietti G.M. , Vagliasindi C. , Forenza N. , Pazzelli P. , Bartolucci M. , Vaccaro R.
Published: October 2009

The expression levels of CD26 and CD31 surface antigens, two adhesion/activation molecules with helper and suppressor activities, respectively, were found to be significantly higher on human colostral T cells (CD3+) than in autologous peripheral blood samples. These findings provide further phenotypical evidence that immune system T lymphocytes are compartmentalized in the mammary gland late in pregnancy and during lactation. The question of whether these overexpanded T lymphocyte populations in breast milk modulate in situ, either by enhancing or suppressing, the cellular and/or humoral immune response of the suckling infant remains to be answered. Additional studies are, therefore, needed to explore this intriguing field concerning the immunology of the colostrum.
Impaired Neutrophil Phagocytosis in Preterm Neonates: Lack of Correlation with Expression of Immunoglobulin or Complement Receptors
Authors: Falconer A.E. , Carr R. , Edwards S.W.
Published: October 2009

Preterm neonates are vulnerable to infection as a result of a compromised immune system. The function of neutrophils from ‘well’, ‘stressed’, and ‘maturing’ preterm neonates was compared with term neonate and adult neutrophils using a whole-blood phagocytosis assay. Cell surface expression of complement receptors and immunoglobulin G receptors was measured on neutrophils in whole blood from the same samples. Fewer actively phagocytosing neutrophils were found in all preterm neonate samples, especially in maturing neonates. Phagocytic rates were slower, and the number of Escherichia coli ingested was smaller in preterm neonate than in term neonate neutrophils. Expression of immunoglobulin G receptors and complement receptor 3 on neutrophils was not directly related to phagocytic activity.
Effect of State of Alertness on the Heart Rate Response to Ocular Compression in Human Infants
Authors: Ramet J. , Hauser B. , Dehan M. , Curzi-Dascalova L. , Gaultier C.
Published: October 2009

Because the state of alertness exerts a profound influence on autonomic cardiac control, we hypothesized, that the heart rate response to a vagal stimulus, i.e., ocular compression, may differ during different states of alertness. We studied 8 healthy infants with a postconceptional age of 35-41 weeks (mean ± SD 37.9 ± 2.1 weeks). They underwent a standardized ocular compression test during polygraphically controlled wakeful-ness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. The R-R intervals were measured (1) during the 60 s preceding the ocular compression test, to determine the mean control R-R interval, and (2) during compression. Percent R-R interval was defined as the longest R-R interval in milliseconds during the test divided by the mean control R-R interval and multiplied by 100. The longest R-R interval during the test was significantly greater in REM sleep than in wakefulness (p < 0.05) and in NREM sleep (p < 0.01): 939 ± 360, 623 ± 355, and 538 ± 60 ms, respectively. The percent R-R interval was significantly greater in REM sleep than in NREM sleep (p < 0.01): 236 ± 91 and 129 ± 16, respectively. The time from the longest R-R interval to return to mean control R-R interval, i.e., vagal escape, was significantly shorter in REM sleep than in NREM sleep and in wakefulness (p < 0.01): 843 ± 168,2,131 ± 712, and 2,078 ± 913 ms, respectively. This study indicates that the state of alertness should be defined when performing tests on autonomic reflexes in infants.
Glucose and Insulin Tolerance Tests in the Rat on Different Days of Gestation
Authors: Muñoz Carmen , López-Luna Pilar , Herrera Emilio
Published: October 2009

To study insulin/glucose relationship during gestation, rats were studied on days 6, 12, 15, 18, 20 or 21 of pregnancy and the results were compared to values in sex-matched virgin control rats. Blood glucose levels were decreased on days 20 and 21 of gestation whereas plasma insulin levels appeared decreased on days 6 and 12, unchanged on day 15 and enhanced on days 18, 20 and 21 of gestation. Total pancreas insulin content was already augmented on day 6 of gestation and continued to increase with gestational time. With the exception of an increase in the 6-day-pregnant rats 22.5 min after an oral glucose load, blood glucose levels did not differ between 6- or 12-day-pregnant rats and virgin controls although plasma insulin levels reached higher values on these days. However, in the 15-day-pregnant rats, glucose tolerance after the glucose load was enhanced while plasma insulin levels did not differ from those in virgin rats during the first 30 min. In the 18-day-pregnant rat blood glucose was more increased but plasma insulin did not differ after the glucose load when compared to virgin rats, whereas 20- or 21-day-pregnant rats showed a glucose tolerance similar to that of virgin rats but their insulin levels shortly after the glucose load were higher. The hypoglycemic response to a high intravenous dose of insulin was decreased in 12-, 18-, 20- and 21-day-pregnant rats. Therefore, whereas in both the 6-and 12-day-pregnant rats there is an enhanced β-cell response to the glucose insulinotropic effect and insulin responsiveness is reduced in 12-day-pregnant rats, the 15-day pregnant rat is in a transitory stage where both insulin sensitivity and the β-cell response return to nonpregnant values. However, from 18 days of gestation on, there is an intense insulin-resistant condition which is only partially compensated by an enormous accumulation of insulin in the pancreas followed by a faster and larger insulin release after a glucose load.
Effect of Acidosis on Bilirubin-Lipid Extract Surfactant Interaction
Authors: Amato Maurizio , Schürch Samuel , Bachofen Hans , Burri Peter H.
Published: October 2009

The risk of bilirubm toxicity in newborn infants with respiratory distress syndrome and hyperbilirubinemia may depend on many factors including pH of the system. Biophysical activity and inhibition characteristics were studied in vitro for lipid extract surfactant (Curosurf, 0.25 mg/ml phospholipids), bilirubin (1.0 mg/ml dissolved in NaOH) and mixed solutions at different pH ranging from 5.0 to 7.4. It was found that unconjugated bilirubin modifies surface tension behavior of lipid extract surfactant films. Maximum and minimum surface tension levels were significantly higher in mixed solutions compared to experiments using pure Curosurf independently from pH. Film area compression for pure Curosurf was not influenced by pH and varied between 22 ± 4% at pH 5.0 and 23 ± 9% at pH 7.4. Adding bilirubin to lipid extract surfactant, area compression to achieve minimum surface tension increased significantly to 83 ± 4% at pH 5.0 and 85 ± 4% at pH 7.4 (p < 0.01). Bilirubin alone showed negligible surface activity independently from pH (83 ± 7% at pH 5.0 and 78 ± 9% at pH7.4) (p > 0.5). We conclude that bilirubin has a detrimental effect on the surface tension properties of lipid extract surfactant in vitro and that this interaction is independent from pH. These data suggest no influence of acidosis on alveolar surfactant system in babies with respiratory distress syndrome and hyperbilirubinemia.
Penile Absorption of EMLA Cream in Piglets: Implications for Use of EMLA in Neonatal Circumcision
Authors: Gazarian Madlen , Taddio Anna , Klein Julia , Kent Geraldine , Koren Gideon
Published: October 2009

EMLA® (eutectic mixture of lidocaine and prilocaine) cream is currently not recommended for use in infants < 1 month of age because of the potential risk of methemoglobinemia as a result of the o-toluidine metabolite of prilocaine. We studied bioavailability and changes in methemoglobin levels following topical penile exposure to 1 g of EMLA cream for 1 hour in piglets. Lidocaine, prilocaine, and o-toluidine concentrations were measured simultaneously using a high-performance liquid chromatography method. The systemic bioavailability of EMLA was low: 4.0 ± (SD) 4.7% for lidocaine (range 0-13.6; n = 8) and 7.2 ± 5.7% for prilocaine (range 0-14.5; n = 8). The ratio between exposure to o-toluidine with EMLA versus intravenous administration (i.e., AUCemla/AUQv; see text) was also low: 4.2 ± 9.3% (range 0–28.6; n = 9). The mean maximum methemoglobin value after intravenous administration was 1.23 ± 0.64% (range 0.5–3.0; n = 12) and after penile application 0.99 ± 0.36% (range 0.5–2.0; n = 12). The methemoglobin value was elevated significantly above baseline after intravenous administration (p = 0.03), but not after penile application of EMLA. These findings suggest that penile administration of 1 g of EMLA may be safe for neonatal circumcision, but further study is required.
Cardiopulmonary Effects of Tumor Necrosis Factor-Alpha in the Piglet: Influence of Cyclooxygenase Inhibition
Authors: Osiovich Horacio , Goldberg Ronald N. , Suguihara Cleide , Adams Jose A. , Martinez Octavio , Kuo George , Feuer William I. , Offenbacher Steven , Bancalari Eduardo
Published: October 2009

Tumor necrosis factor-α (TNF) is believed to play an important role in mediating many of the pathophysiologic changes accompanying bacterial sepsis. In order to characterize the cardiopulmonary responses to TNF in a young animal model and to determine to what extent these changes were secondary to cyclooxygenase byproducts, three groups of mechanically ventilated piglets received an infusion of either TNF, indomethacin followed by TNF (Indo + TNF) or neither (control). Compared to controls at 120 min, TNF resulted in the following changes beginning 30–60 min after the infusion began: mean pulmonary artery pressure (Ppa) increased from 1.7 ± 0.3 to 4.4 ± 0.7 kPa(13 ± 2 to 33 ± 5 mm Hg) (p < 0.001); cardiac output (CO) fell from 0.28 ± 0.05 to 0.20 ± 0.07 liters/kg/min (p < 0.01); mean arterial blood pressure (Psa) decreased from 9.5 ± 1.2 to 7.9 ± 1.9 kPa(71 ± 9 to 59 ± 14 mm Hg) as did pH from 7.49 ± 0.04 to 7.13 ± 0.17 (p < 0.001). Dynamic lung compliance (Cdyn) also decreased; however, pulmonary resistance (RI) remained unchanged. Thromboxane B2 (TxB2) rose in all animals at 60 min coincident with Psa elevation and was significantly blocked by Indo (p < 0.03). In the Indo + TNF group the early TNF-induced rise in Psa was blunted compared to the TNF group [2.9 ± 1.2 vs. 3.6 ± 0.8kPa(22_ ± 3 vs. 27 ± 6 mm Hg; p < 0.04)] as were the late decreases in pH and Psa (p < 0.04). There were no significant changes in Cdyn secondary to Indo. Although delayed, the hemodynamic changes observed with TNF infusion are similar to those reported for piglets receiving group B streptococci; however, in contrast to the latter the early changes secondary to TNF are only mildly effected by indomethacin. The significant improvement in the late occurring hypotension and acidosis suggests that TNF may act in part via the cyclooxygenase pathway as a mediator of the late hypotension associated with sepsis.
Insulin-Like Growth Factor 1 and Parathyroid Hormone Effects on the Growth of Fetal Rat Metatarsal Bones Cultured in Serum-Free Medium
Authors: Coxam V. , Miller M.A. , Bowman B.M. , Qi D. , Miller S.C.
Published: October 2009

Insulin-like growth factor 1 (IGF-1) has roles in bone growth, and parathyroid hormone (PTH) is suspected of having effects on bone, perhaps mediated by IGF-1. The purpose of this study was to determine the individual and combined effect of PTH and IGF-1 on fetal long bone metabolism. Three medial metatarsal bones were dissected from Sprague-Dawley rat fetuses harvested at the 19th day of gestation, then grown in serum-free MEM. IGF-1 (group II) or PTH (group PP) were added at the dose of 100 ng/ml for 8 days. In a third group (PI), bones were preincubated for 4 days with PTH followed by a 4-day incubation with IGF-1. Both hormones stimulated endochondral (longitudinal) growth, the highest effect was observed with IGF-l(II:3.11 ± 0.06vs.2.16 ± 0.08 mm in controls). The length elicited by the PI treatment ranged between those measured with IGF-1 (II) and PTH (PP) given alone (PI: 2.80 ± 0.04 mm; PP: 2.57 ± 0.06 mm). In addition, both hormones enhanced periosteal growth (endomembranous ossification), as measured by the width of bones (II: 0.39 ± 0.02 mm; PP: 0.34 ± 0.02 mm; PI: 0.38 ± 0.02 vs. 0.29 ± 0.01 mm in controls). On the other hand, IGF-1 but not PTH caused a significant increase in 35S incorporation (as an indicator of sulfated proteoglycan synthesis in cartilage (percent of incorporating activity; II: 0.18 ± 0.04%; PI: 0.09 ± 0.01 vs. 0.03 ± 0.01% in controls). Nevertheless, both IGF-1 and PTH enhanced osteoblastic activity as shown by increased alkaline phosphatase activity in treated bones (II: 1.18 ± 0.00 μmol/bone; PP: 0.50 ± 0.00 vs. 0.28 ± 0.00 μmol/bone). In conclusion, IGF-1 had the greatest effects on growth in bone length (endochondral osteogenesis) and bone width (intramembranous osteogenesis) and appeared to stimulate both chondrogenesis and osteogenesis. It also increased growth but appeared to have greater effects on osteogenesis than on chondrogenesis. Pretreatment with IGF-1 followed by PTH produced effects that were intermediate between the groups treated with IGF-1 and PTH alone.
Brain and Respiratory Cilia: The Effect of Temperature
Authors: O’Callaghan Christopher , Achaval Marcelo , Forsythe Ian , Barry Peter W.
Published: October 2009

We have used a modified photodiode method to measure ciliary beat frequency of human neonatal cilia, and have developed techniques to allow similar measurements of rat brain cilial function. The effect of temperature change, within the physiological range, on neonatal human respiratory cilia and neonatal rat brain cilia was studied. The mean (SD) ciliary beat frequency of neonatal respiratory cilia at body temperature was 14 (1.1) Hz and that of rat brain cilia 18.9 (1.3) Hz. Respiratory cilial beat frequency decreased by 9.1% and brain cilia by 13% on cooling to 32 °C compared to normal body temperature. Beat frequency increased by 8.5% in respiratory samples and by 12% in brain samples on warming to 40 °C compared to the frequency at normal body temperature. The Q10 of human neonatal respiratory cilia was 1.2 and that of rat brain cilia 1.3.
Predicting the Need for Phototherapy in Healthy Mature Neonates Using Transcutaneous Bilirubinometry on the First Postnatal Day
Authors: Knudsen Aage
Published: October 2009

Since newborn infants are frequently sent home within 24–48 h after birth, the prediction of severe hyperbilirubinaemia, requiring treatment, is important. We tested the prediction of the need for phototherapy by measuring the yellow skin colour and the progression in yellow skin colour over 6 h using transcutaneous bilirubinometry (TcB), during the first 33 h of age. The first TcB reading at median 21 h (11–33 h, 5th and 95th percentiles) of age and the difference in readings over a 6-hour interval were reliable predictors of later phototherapy. An even better prediction was possible using the first TcB reading and the 6-hour difference in TcB readings.
Hemodynamic Adaptations at Birth and Neonates Delivered Vaginally and by Cesarean Section
Authors: Agata Youtaro , Hiraishi Satoshi , Misawa Hitoshi , Han Jae Hee , Oguchi Koki , Horiguchi Yasunori , Fujino Nobuyuki , Takeda Nobuhiro , Padbury James F.
Published: October 2009

In order to assess the possible influence of differences in delivery mode on cardiovascular adaptation at birth, we measured left ventricular output and its regional distribution in the major organs sequentially using an echographic technique during the first 96 h of life. We studied 27 normal newborns, of whom 15 were delivered vaginally and 12 by cesarean section. We also measured umbilical arterial and venous catecholamine concentrations. The umbilical arterial epinephrine and norepinephrine concentrations in the infants delivered vaginally were significantly greater than those in the infants delivered by cesarean section (epinephrine 1,195 ± 208 vs. 565 ± 81 pg/ml p < 0.05; norepinephrine 11,832 ± 3,819 vs. 5,153 ± 1,400 pg/ml, p < 0.05). The left ventricular output and its regional distribution showed a similar pattern in the two groups, and there were no significant differences between them. These results indicate that the capacity of infants delivered by cesarean section to tolerate cardiovascular changes during the early neonatal period is comparable to that in infants delivered vaginally, even though there are significant differences in the catecholamine surge between these groups.