bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Mineral Status in Preterm-Born Children: Assessment by Dual-Energy X-Ray Absorptiometry
Authors: Hori Chikahide , Tsukahara Hirokazu , Fujii Yasushi , Kawamitsu Tooru , Konishi Yukuo , Yamamoto Kazutaka , Ishii Yasushi , Sudo Masakatsu
Published: October 2009

To elucidate the long-term consequences of osteopenia of prematurity, lumbar spinal bone mass was measured in 21 preterm-born children aged 3-4 years by dual-energy X-ray absorptiometry. Their mineral intake remained low during early life, and all 11 infants previously studied were osteopenic at term postconception. At the age of 3–4 years, however, all 21 children were found to have normal bone mineral content and density with slightly elevated serum osteocalcin levels. Our results show that in preterm-born children spontaneous resolution of lumbar spinal osteopenia occurs during early childhood.
Paediatric Clinical Pharmacology in the Former Soviet Union: Ukraine
Authors: Rieder Michael J.
Published: October 2009

Among the many challenges facing the newly created states formed in Eastern Europe and Central Asia after the collapse of the Soviet Union is the development of medical education and health care independent of many of their former ties to Moscow. Ukraine, the largest of these states following the Russian Republic, is facing many of these challenges. Paediatric clinical pharmacology is markedly underdeveloped in the Ukraine. There is little clinical pharmacology content in undergraduate medical education and essentially none in postgraduate training. Underdevelopment of paediatric clinical pharmacology also increases difficulties faced because of lack of a domestic pharmaceutical industry. This situation compounds the difficulty of how physicians in Ukraine can best learn to choose and apply rational individualized therapy.
Molecular Forms of Atrial Natriuretic Peptide in Atria and Plasma from Fetal and Adult Female Rats
Authors: Deloof S. , Van Camp G. , Chatelain A.
Published: October 2009

Molecular forms of atrial natriuretic peptide (ANP) were determined by chromatography on Sephadex G50 fine coupled with a radioimmunoassay for rANP(1-28)m left and right atrial extracts and acidified plasmas from 17-, 19- and 21-day-old fetuses and adult female rats. Chromatographic analyses revealed two immunoreactive peaks of rANP with an apparent molecular weight of about 25 and 12 kD, respectively, in all atrial extracts from fetal and adult rats. Only one immunoreactive peak of rANP with an apparent molecular weight of about 3 kD was detected in all fetal plasmas. The 25- and 12-kD ANP molecular forms isolated from fetal atrial tissue and incubated with thrombin for 30 min at 37°C were converted to ANP material with a molecular weight of about 3 kD. These results suggest that the two high molecular weight forms stored in fetal atrial tissue should be precursors of circulating rANP molecules, and the rat fetus should possess the same posttranslational processing of the precursor molecule as the adult rat as early as day 17 of gestation.
Membrane Antigen and Ligand Receptor Expression on Neonatal Monocytes
Authors: El-Mohandes Ayman A.E. , Rivas Richard A. , Kiang Eileen , Wahl Larry M. , Katona Ildy M.
Published: October 2009

The monocyte/macrophage cell lineage is an essential component of host defense. Functional deficiencies have been described in neonatal monocytes, but knowledge of membrane antigen and receptor ligand expression in neonatal monocytes is incomplete. In this study, antigen and receptor ligand expression of cord blood monocytes (CBM) was examined and compared to adult peripheral blood monocytes (PBM). Leu-M3 and Leu-M5 antigens were shown to be present on all CBM. Using dual fluorescence microfluorometry, the percentage and intensity of expression of HLA-DR, CD4 antigens, Fcγ and IL-2 receptors (IL-2R) on Leu-M3+ and Leu-M5+ CBM were compared to PBM. A lower percentage of expression of HLA-DR+ (87 ± 3% vs. 95 ± 1%, p = 0.02) and FCγRII+ (96 ± 1% vs. 99 ± 0.2%, p = 0.04) was noted on CBM. CD4, FCγRI, and FCγRIII expression on CBM were comparable to PBM. LPS stimulation of CBM induced IL-2R expression and enhanced HLA-DR antigen expression as seen previously on PBM. These findings indicate that CBM are phenotypically comparable to adult PBM with deficiencies localized only to a few specific areas.
Impact on Blood Pressure and Intestinal Pertusion of Dobutamine or Dopamine in Hypotensive Preterm Infants
Authors: Hentschel Roland , Hensel Dirk , Brune Thomas , Rabe Heike , Jorch Gerhard
Published: October 2009

In a prospective study hemodynamic effects of dobutamine or dopamine (10 μg/kg/min) were investigated in 20 preterm infants who had protracted arterial hypotension refractory to volume therapy. Doppler ultrasonography of the superior mesenteric artery (SMA) was applied to verify intestinal perfusion and blood pressure was recorded in parallel. Mean arterial pressure (MAP) raised significantly in both groups (from 31.0 ± 6.8 to 37.7 ± 9.8 mm Hg during dobutamine and from 27.7 ± 3.6 to 36.0 ± 9.3 mm Hg during dopamine). Mean blood flow velocity increased from 25.8 ± 13.5 to 31.5 ± 16.5 cm/s with dobutamine and from 16.3 ± 5.0 to 19.0 ± 6.0 cm/s with dopamine (significant for dobutamine). Vascular resistance of SMA (indicated by resistance index; RI) decreased from 0.81 ± 0.07 to 0.74 ± 0.11 for dobutamine and from 0.89 ± 0.06 to 0.79 ± 0.07 for dopamine (significant for both groups). These data indicate that in the dose tested here both catecholamines are equally effective in raising MAP and lead to a significant increase of intestinal perfusion. Thus, a negative impact on mesenteric blood supply, predisposing to necrotizing enterocolitis, is not probable.
Variation in the Biochemical Forms of Transforming Growth Factor-α Present in Human Milk and Secreted by Human Milk Macrophages
Authors: Wagner Carol L. , Forsythe Donna W. , Pittard William B.
Published: October 2009

Objective: Transforming growth factor-α (TGF-α), present in human milk, is thought to play a significant role in postnatal gut development. Macrophages, which abound in human milk, are known to secrete various isoforms of TGF-α in other areas of the body. It was hypothesized that human milk macrophages (HMM) secrete TGF-α, and HMM are a source of TGF-α isoforms present in human milk. We sought to measure in vitro HMM TGF-α secretion, and to compare the TGF-α isoform(s) present in human milk with those secreted by HMM. Study Design: Colostrum and mature milk samples, obtained from mothers (n = 48) on postpartum days 3-30, were centrifuged. HMM were isolated, placed in culture for 24 h, and cell-free media collected. The biochemical forms of TGF-α in media in human milk supernatant samples were identified by Western blot analysis under reducing conditions. The concentration of the mature (6-kD) TGF-α isoform in those samples was quantified using a radioimmunoassay. Results: Western blot analysis under reducing conditions identified a single 6-kD TGF-α isoform in all human milk supernatant samples tested, but variable (6- and 30- to 46-kD) TGF-α isoforms in HMM media. The mean (± SE) concentration of the 6-kD TGF-α isoform found in human milk supernatants was 706 ± 88 pg/ml and 17.6 ± 2.6 pg/ml in HMM media. Conclusion: These experiments show that HMM secrete TGF-α in biochemical forms both similar to and distinct from that found in human milk supernatant.
Insulin-Like Growth Factor I Absorption in the Jejunum of Neonatal Calves
Authors: Vacher P.-Y. , Bestetti G. , Blum J.W.
Published: October 2009

The absorption of recombinant human insulin-like growth factor I (rhIGF-I), [125I]rhIGF-I, xylose and [3H]lysine, administered into a clamped jejunal segment in anesthetized neonatal calves, was studied by measuring their appearance in the mesenteric vein draining the gut segment. Only trace amounts of IGF-I and of [125I]rhIGF-I and/or 125I were absorbed following dissolution in saline, buffer or colostrum. The absorption rate of both [3H]lysine and/or 3H and of xylose was much greater than the absorption of rhIGF-I, [125I]rhIGF-I and/or 125I but was also transient. Biological effects of ingested IGF-I in neonatal calves should barely occur as a consequence of intestinal absorption even in 1-day-old calves, known to absorb various peptides and proteins.
Umbilical Cord Osteocalcin in Normal Pregnancies and Pregnancies Complicated by Fetal Growth Retardation or Diabetes mellitus
Authors: Verhaeghe Johan , Van Herck Erik , Bouillon Roger
Published: October 2009

A homologous radioimmunoassay for human osteocalcin was used to measure cord serum osteocalcm concentrations in normal pregnancies and in pregnancies complicated by intrauterine growth retardation (IUGR) and diabetes. The mean osteocalcin concentrations in term newborns (100–110 μg/l) were comparable with levels that we previously measured in pubertal children. There was a small increase in mean osteocalcin concentrations during the third trimester of fetal life, with the maximum at 35 weeks; between weeks 36 and 41, the osteocalcin levels dropped by 13%. Osteocalcin was 20% lower in IUGR neonates than in age- or weight-matched newborns. The newborns of diabetic mothers had markedly lower osteocalcin concentrations than the weight-matched neonates, and 16 of the 19 samples were more than 1 SD below the mean of the gestational-age osteocalcin regression curve. Cord serum osteocalcin appears to be a useful parameter in studying normal and abnormal fetal mineralization.
Maternal Obesity and Body Composition of the Neonate
Authors: Silliman Kathryn , Kretchmer Norman
Published: October 2009

Obese women generally deliver heavier infants, but the body composition of these infants is unknown. The principal objective of this study was to determine if neonates of obese women have more adipose tissue. At 35–36 weeks of gestation, a fasting blood sample was collected from 37 pregnant women. Shortly after birth, the body fat of the neonates was measured with an infant total-body electrical conductivity (TOBEC) instrument using a prediction equation derived from 10 miniature pigs. At 6 weeks post partum, the infant body fat was measured a second time, and the body fat of each mother was measured using an adult TOBEC instrument. We found no differences between the obese (n = 16) and lean subjects (n = 21) in the concentrations of glycerol, β-hydroxybutyrate, triglyceride, total cholesterol, high-density lipoprotein cholesterol, or glucose in the blood. However, the insulin concentration was elevated in the obese women (199 ± 57 pmol/l) as compared with the lean women (128 ± 68 pmol/l, p < 0.01). At birth, maternal adiposity (% body fat) was significantly associated with infant adiposity (r = 0.37, p < 0.05). However, by 6 weeks post partum the association no longer existed. Multiple regression analysis showed that maternal adiposity, fasting glucose level, and gestational age are independently associated at birth with infant adiposity.
Recombinant Human lnterleukin-3 Enhances the in vitro Survival of Mononuclear Phagocytes from the Peripheral Blood of Very Low Birth Weight Premature Infants at Birth
Authors: Omar Said A. , Fleit Howard B. , Kobasiuk Catherine D. , La Gamma Edmund F.
Published: October 2009

Interleukin 3 (IL-3) is a pluripotent hematopoietic growth factor that stimulates proliferation, differentiation, and function of multiple cell lineages. We examined the effects of recombinant human IL-3 (rhIL-3) on peripheral blood mononuclear cells (MNC) isolated from 18 premature human newborns with birth weights between 600 and 1,500 g at birth and at 2 and 4 weeks of age, from 7 full-term neonates, and from 26 normal adult volunteers. After 2 weeks in liquid culture, rhIL-3 treatment was associated with a six- to nine-fold increase in the survival of MNC from very low birth weight (VLBW) neonates. In the absence of rhIL-3, VLBW neonatal MNC exhibited a low survival rate. MNC from 6 of 7 full-term neonates responded similarly to rhIL-3 with an eight-fold increase in survival. In contrast, rhIL-3 showed only a 20–30% increase in the survival of adult MNC (p = NS). When analyzed by immunofluorescent microscopy using monoclonal antibodies to phenotypic markers characteristic of individual MNC lineages, 70–80% of the surviving VLBW neonatal MNC were mononuclear phagocytes, while 70–80% of the surviving adult MNC were T cells. Full-term MNC cultures displayed a population of cells with an intermediate phenotype. Following rhIL-3 treatment, surviving MNC from term neonates displayed 35% T cells and 53% mononuclear phagocytes which was not significantly different from untreated MNC. rhIL-3 treatment was associated with a seven- to twelve-fold increase in the number of progenitor cells (CD34+) from VLBW neonatal blood and a three- to five-fold increase in the number of adult progenitor cells. Full-term neonates had a lower percentage of CD34+ cells than VLBW neonates, and this was not significantly altered by the rhIL-3 treatment. We conclude that rhIL-3 increases the number of mononuclear phagocytes that survive in culture following isolation from the peripheral blood of VLBW neonates. These in vitro studies may have a predictive value for in vivo studies utilizing combinations of hematopoietic growth factors to enhance neonatal host defense.
Peroxisomes and Peroxisomal Enzymes in the Human Fetal Small Intestine
Authors: Dauça Michel , Cable Sylvie , Calvert Raymond , Colin Suzanne , Schilt Joseph , Leheup Bruno , Keller Jean Marie , Ménard Daniel
Published: October 2009

The appearance and development of peroxisomes and the expression of their enzymes in the human fetal intestine have been investigated between 11 and 22 weeks of gestation. In the youngest samples (11-16 weeks of age), cytochemistry at the ultrastructural level revealed the presence of rare, mostly circular peroxisomes. From 16 weeks of gestation onwards, an increase was noted in the number of peroxisomes. Two peroxisomal types were distinguished: round to oval forms and elongated and/or tailed organelles. Biochemical assays revealed that total and specific intestinal catalase activities increased gradually between 11 and 20 weeks of gestation. The activity of fatty acyl-CoA oxidase, the first enzyme of the peroxisomal β-oxidation system, was detectable as early as 11 weeks of gestation. Thereafter, total and specific activities of the enzyme increased steadily. Activities of other peroxisomal oxidases (D-amino acid oxidase, L-α-hydroxyacid oxidase) appeared more slowly in the fetal intestine during the period studied. This investigation establishes the presence and the morphological changes that occur in intestinal peroxisomes during human fetal development as well as the developmental patterns of associated enzymes.
Umbilical Cord Dopamine β-Hydroxylase, Chromogranin A and Met-Enkephalin after Conditions Associated with Chronic Intrauterine Stress
Authors: Van Reempts Patrick J. , Wouters An , Laroche Sabina , Pinxteren Jef , De Potter Werner , Vanderauwera Jean-Claude , Van Acker Karel J.
Published: October 2009

Objective: To evaluate whether the markers of autonomic nervous system activity, dopamine β-hydroxylase (DBH), chromogranin A (CGA) and met-enkephalin (E), are different in cord blood from neonates born after conditions associated with chronic intrauterine stress (CIUS) as compared to neonates born after a normal pregnancy. Study design: 61 newborns (median BW 2,840 g, range 617–4270 g) born after a pregnancy complicated by maternal hypertension, maternal smoking, maternal diabetes mellitus or intrauterine growth retardation (STR group) were compared with 88 neonates (median BW 2,910 g, range 4,00–4,370 g) who had not suffered from such intrauterine conditions. DBH, CGA and E were measured in the cord blood of both groups. Results: When both groups were taken together, high DBH values were best related to maternal smoking (p = 0.004) and low E levels to maternal diabetes (p = 0.02). Within the STR group, high DBH values were best related with all conditions linked with CIUS (p = 0.008), E levels were best linked with the combination of intrauterine growth retardation (positive correlation) and maternal diabetes (negative correlation) (p = 0.03). For CGA there was only a weak positive relation with maternal smoking (p = 0.3). Conclusion: Certain intrauterine conditions associated with CIUS, especially maternal smoking, may lead to alterations of the autonomic nervous system as revealed by some of its markers in cord blood of neonates. This may be important in the pathogenesis of certain conditions after birth, such as the sudden infant death syndrome.
Interactive Effects of Thermal Environment and Energy Intake on Thyroid Hormone Metabolism in Newborn Pigs
Authors: Berthon D. , Herpin P. , Le Dividich J. , Dauncey M.J.
Published: October 2009

The aim of the study was to determine the effects of 48-hour cold exposure (25 vs. 34°C), starting at 6 h of age, and energy intake on thyroid hormone plasma levels, hepatic 5′-deiodinase activity and nuclear 3,3′,5-triiodothyronine (T3) receptors in newborn pigs. In the cold, piglets were fed either a similar milk intake (C piglets) to the piglets at thermal neutrality (TN piglets) or were given an extra amount of milk to compensate for the increased heat production (C+ piglets). Concentrations of plasma thyroxine (T4) decreased steadily over the 48-hour investigation and were affected neither by ambient temperature nor by energy intake. At the end of 48 h, plasma levels of T3 and liver 5’-deiodinase activity were similar in TN and C+ piglets and higher than in C piglets. The numbers of T3 receptors were greater in the liver from C and C+, as well as in skeletal muscle from C, than from TN piglets. Results of the study suggest that plasma T3, liver 5′-deiodinase and liver nuclear T3 receptors of the newborn pig can be regulated by energy intake and ambient temperature.
Prolactin and Growth Hormone in Perinatal Asphyxia
Authors: Varvarigou Anastasia , Vagenakis Apostolos G. , Makri Maria , Frimas Constantinos , Beratis Nicholas G.
Published: October 2009

To assess the pituitary response to perinatal asphyxia, the prolactin (PRL) and growth hormone (hGH) serum concentrations were measured in 55 asphyctic (15 preterm and 40 full-term) and 35 control (15 preterm and 20 full-term) newborns at 2-4,24,48 and 96 h of life. At 2-4 h the median PRL in the preterm asphyctic neonates was 5.2 U/l, whereas in the preterm control newborns it was 3.2. In the full-term newborns with and without hypoxic-ischaemic encephalopathy (HIE) it was 5.8 and 3.4, respectively. In the full-term neonates with HIE the PRL remained significantly higher than in the controls up to the fourth day. At 2–4 h the median hGH in the preterm asphyctic and control newborns was 106.2 and 54.8 mU/l, respectively. In the full-term newborns it was 85.0 and 40.8, respectively. The lowest hGH concentrations were found in the severe HIE. The increased PRL and hGH in asphyxia may result from a stress-related hormone release, whereas the very low hGH concentrations in severe HIE may result from a damage at the hypothalamic-hypophyseal axis.
Lung Hypoplasia and Surfactant System Immaturity Induced in the Fetal Rat by Prenatal Exposure to Nitrofen
Authors: Alfonso Luisa F. , Arnaiz Arantzazu , Alvarez Francisco J. , Qi Baoquan , Diez-Pardo Juan A. , Vallis-i-Soler Adolf , Tovar Juan A.
Published: October 2009

We studied the biochemical maturity of the lungs of fetuses born to rats exposed to nitrofen on day 9.5 of gestation. In comparison with controls, nitrofen-treated fetuses had pulmonary hypoplasia (decreased lung/body weight), lung hypocellularity (low DNA content) and cellular atrophy (low protein/ DNA and phospholipid/DNA) on gestational days 19 and 21. Treated animals with congenital diaphragmatic hernia (CDH) also had cell atrophy and surfactant immaturity (decreased disaturated phosphatidylcholine/DNA) near term. Our data demonstrate that nitrofen causes lung hypoplasia and some degree of surfactant system immaturity that is particularly prominent in fetuses with CDH.
The Development of Preatherosclerotic Coronary Artery Lesions in Perinatal Piglets
Authors: Bolande Robert P. , Leistikow Elizabeth A. , Wartman III Franklin S. , Louis Thomas M.
Published: October 2009

The fine structure and ultrastructure of the anterior descending coronary artery were studied in a series of perinatal piglets at 1 week prior to birth, and at 8, 24, 72 and 168 h after birth. In the anterior descending coronary artery, at or just distal to the branch point of the left circumflex artery, early plaque-like intimal lesions were present in the majority of animals. These consisted of subendothelial edema, fragmentation and dissolution of the internal elastic lamella, and the appearance of intimal myoid cells known as modified smooth muscle cells (MSMCs). These changes were present in all piglets at and before 8 h of age. They persisted and progressed during the first week of life in about half of the piglets. Beginning at 72 h and continuing through 168 h, there was an increase in MSMCs and the appearance of fibroblasts. Both fibroblasts and MSMCs were associated with the elaboration of dense collagen fibrils. Foamy macrophages appeared within the subendothelial intima having the appearance of lipophages. While the prevalence of these changes at birth indicates that they may be part of normal development, their persistence in half the piglets and structural features suggest reaction to intimal injury beginning prenatally. The lesions may be precursive of coronary atherosclerosis later in life and may parallel the early stages of atherogenesis in humans.
Rapid Tracheal Infusion of Surfactant versus Bolus Instillation in Rabbits: Effects on Oxygenation, Blood Pressure and Surfactant Distribution
Authors: Segerer Hugo , Scheid Annette , Wagner Mathias H. , Lekka Marilena , Obladen Michael
Published: October 2009

Surfactant bolus instillation may be associated with a drop in blood pressure. Platelet-activating factor (PAF) has been found in surfactant preparations. The aim of this study was to evaluate rapid tracheal infusion of surfactant during 5 min as an alternative to bolus instillation and to examine whether a PAF receptor antagonist is able to prevent the decrease in blood pressure. Methods: Surfactant deficiency was induced in 16 adult rabbits by lung lavages with saline. Six animals received a bolus of a porcine surfactant preparation (Curosurf® (CS); 200 mg/kg), labeled with red microspheres to assess pulmonary distribution. In another 5 rabbits, the same amount of labelled CS was instilled by tracheal infusion within 5 min. A third group of 5 animals received 3 mg/kg body weight of the PAF antagonist WEB 2170 before CS bolus instillation. Results: After CS bolus administration, mean PaO2 increased by 44.7 ± 8.3 kPa (mean ± SD) within 2 min and remained at this level. Mean arterial blood pressure dropped transiently by 2.3 ± 2 kPa within 5 min. Pulmonary distribution of surfactant was even. After infusion, mean PaC2 rose by 22.4 ± 16.3 kPa within 15 min. Blood pressure dropped by 1.8 ± 1.1 kPa within 15 min. The distribution was extremely uneven. Blood pressure decreases also occurred after pretreatment with PAF receptor antagonist. Conclusion: Rapid tracheal infusion of surfactant results in poorer oxygenation, an inhomogeneous distribution and a similar decrease in blood pressure compared to the bolus instillation method. Blood pressure changes could not be prevented by a PAF receptor-specific antagonist.
Effects of Chloral Hydrate on the Cardiorespiratory Response to Hypoxia in Newborn Piglets
Authors: Yu Xiang-Qing , Suguihara Cleide , Navarro Hugo , Hehre Dorothy , Huang Jian , Bancalari Eduardo
Published: October 2009

To assess the effects of chloral hydrate (CH) on the cardiorespiratory response to hypoxia in the neonate, 17 newborn piglets were chronically instrumented 48–72 h before study and randomly assigned to a CH group (100 mg/kg, i.p.) or saline group. The animals were intubated and studied under quiet sleep which was determined by behavioral states, and continuous electro-oculographic and electroencephalographic monitoring. Minute ventilation (VE), tidal volume, respiratory rate, arterial blood gases (ABG), oxygen consumption (VO2), arterial blood pressure (ABP) and heart rate (HR) were measured before and after CH or saline administration during room air and after 10 min of hypoxia (fraction of inspired oxygen concentration = 0.10). Cardiorespiratory response to hypoxia was similar before and after saline infusion. Basal VE and the ventilatory response to hypoxia were similar before and after CH administration. In contrast, the basal ABP decreased significantly (p < 0.05) after CH administration, but the ABP response to hypoxia was similar before and after CH. A significant increase in both basal HR and HR with hypoxia was observed after CH administration. In addition, VO2 and ABG were not modified by CH treatment during normoxia and hypoxia. These data demonstrate that a sedative dose of CH does not significantly modify the ventilatory response to hypoxia in newborn piglets. However, CH produced some changes in the cardiovascular system which should be considered when using it in infants with hemodynamic derangements.
Antenatal Glucocorticoid Treatment Attenuates Immediate Postnatal Prostacyclin and Thromboxane Levels in Plasma of Very Preterm Lambs
Authors: Ibe Basil O. , Okogbule-Wonodi Adora C. , Raj Usha
Published: October 2009

The effect of antenatal glucocorticoid treatment on the production of cyclooxygenase metabolites was studied in very preterm lambs. Seven fetal lambs, 121 days of gestation, received a single dose of betamethasone, 0.5 mg/kg i.m., 48 h prior to delivery. Five age-matched controls received saline intramuscularly. Each fetus was delivered and ventilated for 3 h and sacrificed. Plasma was prepared from blood drawn from the umbilical cord of each fetus, and 60, 120 and 180 min after delivery. Mesenteric (MESA) and femoral (FEMA) arteries were isolated and incubated in Krebs’ buffer for 10 min at 37°C. Samples were extracted for prostacyclin (PGI2), and thromboxane (Tx)A2, purified by HPLC and measured by specific radioimmunoassay. Amounts of metabolites measured postnatally from betamethasone-treated preterm lambs were significantly lower (p < 0.05) than the amounts from saline lambs. Prostacyclin production by MESA and FEMA of betamethasone-treated lambs was lower than by vessels of saline-treated lambs. There was no difference in TxA2 production by vessels from the two groups of preterm lambs. Our data show that antenatal betamethasone treatment decreased systemic prostanoid production suggesting a decreased reactivity of the vascular membrane.
Effect of Subadequate Maternal Vitamin-A Status on Placental Transfer of Retinol and Beta-Carotene to the Human Fetus
Authors: Dimenstein R. , Trugo N.M.F. , Donangelo C.M. , Trugo L.C. , Anastácio A.S.
Published: October 2009

The placental transfer of retinol and β-carotene was assessed based on maternal serum, cord serum and placental levels at term parturition in women with adequate (n = 15; serum retinol > 20 μg/dl) and subadequate (n = 16; serum retinol ≤ 20 μg/dl) vitamin-A status. There was no difference in retinol and β-carotene levels in placenta and cord serum between these groups. However, differences in the relation of maternal, placental and cord blood components were observed between women with adequate and subadequate vitamin-A status. In women with subadequate status, circulating fetal retinol levels correlated with placental retinol levels, and maternal serum β-carotene correlated with placental retinol. Within this group, maternal serum β-carotene and cord serum retinol correlated significantly in women with serum retinol levels lower than 15 μg/dl. These results suggest that β-carotene may be a precursor of retinol in placenta and that this conversion may depend on the nutritional status of the mother, being particularly effective in a more depleted state.
Hypoxic-Ischemic Injury Acutely Disrupts Microtubule-Associated Protein 2 Immunostaining in Neonatal Rat Brain
Authors: Malinak Christa , Silverstein Faye S.
Published: October 2009

We evaluated the influence of an acute hypoxic-ischemic insult on the neuronal dendritic cytoskeletal protein microtubule-associated protein 2 (MAP2) in the immature rat brain. Studies were performed using a well-characterized perinatal rodent stroke model, in which unilateral ischemic forebrain injury was induced in 7-day-old rats by right carotid artery ligation, followed by 3 h exposure to 8% oxygen. Changes in the neuroanatomic distribution of MAP2 in the first 48 h after injury were evaluated by immunocytochemistry with a monoclonal mouse anti-MAP2 antibody. The distribution of MAP2 immunoreactivity was markedly disrupted in the lesioned hippocampus; prominent reductions in MAP2 immunostaining evolved concurrently in lesioned cortex, caudate and thalamus. These data demonstrate that at this developmental stage, MAP2 immunocytochemistry provides a sensitive indicator of the distribution and severity of hypoxic-ischemic neuronal injury.
Hemolytic Anemia Does Not Increase Entry into, nor Alter Rate of Clearance of Bilirubin from Rat Brain
Authors: Ruud Hansen Thor Willy , Allen Jeffrey W.
Published: October 2009

The risk of bilirubin encephalopathy is believed to be increased in hemolytic relative to nonhemolytic jaundice. Young SPRD rats were injected with either acetylphenylhydrazine (APHZ, n = 22) 75 mg/kg or an equivalent volume of the solvent (control, n = 22) intraperitoneally for 3 successive days. One the 4th day, hyperbilirubinemia was induced by a 5-min intravenous infusion of 50 mg/kg bilirubin. After sacrifice (at 10 or 60 min) the brain vessels were flushed in situ with ice-cold saline. Serum bilirubin was 600 ± 108 μmol/l (mean ± SD) at 10 min, and 295 ± 98 μmol/l at 60 min. Hematocrit was significantly reduced in the APHZ rats versus controls (26 ± 3 vs. 41 ± 3, p < 0.0001). The concentration of bilirubin in brain was determined by acid chloroform extraction and diazotization. The brain bilirubin values were 5.5 ± 1.5 versus 5.4 ± 2.1 mmol/gat 10 min (APHZ vs. control), and 1.3 ± 0.6 versus 0.8 ± 0.7 nmol/g at 60 min. The half-life of bilirubin in brain was calculated with an exponential fitting program. The half-life of bilirubin in brain for the two groups was 24.3 ± 21.9 versus 18.5 ± 28.3 min. There were no significant differences between the groups in either of these measures. We conclude that in young rats, hemolytic anemia does not increase the acute entry of bilirubin into brain, nor does it affect the clearance of bilirubin from brain.
Comparison of Natural Surfactant and Brief Liquid Ventilation Rescue Treatment in Very Immature Lambs
Authors: Valls-i-Soler Adolf , Wolfson Marla R. , Kechner Nancy , Foust Ray , Shaffer Thomas H.
Published: October 2009

We studied the effect of rescue therapy with modified porcine surfactant (Curosurf®) or brief perfluorocarbon liquid ventilation on pulmonary gas exchange, mechanics and structure in very immature lambs. Both rescue strategies produced an improvement in arterial oxygenation and were able to support CO2 elimination. Histology showed unevenly inflated lungs in all but tidal-liquid-ventilated lambs. We speculate that due to immature lung architecture and relatively high permeability, previous exposure to gas ventilation impeded full effectiveness of both rescue modalities, perhaps prophylactic surfactant or liquid ventilation could be a better alternative.
Inhalation of Nitric Oxide: Effect on Cerebral Hemodynamics and Activity, and Antioxidant Status in the Newborn Lamb
Authors: Lopes Cardozo Robbert H. , de Beaufort Arnout Jan , Gesink Birthe J. , Moison Ralph M.W. , van de Bor Margot , Berger Howard M. , van Bel Frank
Published: October 2009

Ventilation with nitric oxide (NO) is increasingly being used to treat pulmonary hypertension in the newborn. In the brain, NO has vasoactive properties and is involved in neurotransmission. However, the effect of inhaled NO on the cerebral blood flow (CBF) and on the cerebral activity is not known. Furthermore, there is little information on the influence of this free radical gas on the redox status in pulmonary vessels. We therefore investigated the effect of inhaled NO (2–60 ppm) on CBF, cerebral activity and redox status in blood effluent from the pulmonary circulation in 6 ventilated newborn lambs before and during group B streptococci (GBS)-induced pulmonary hypertension. Blood pressure in the pulmonary artery (Pap) and aorta (Pao), carotid artery blood flow (Qcar) to assess changes in CBF, and electrocortical activity were measured. Blood gases, indices of free radical status and methemoglobin were determined in blood samples obtained from the left ventricle. Inhalation of NO, before and during GBS-induced pulmonary hypertension, decreased Pap and PCO2 and increased PO2. Multiple linear regression revealed that Qcar was positively related to PCO2, but not to inhaled NO or PO2 before or during GBS conditions. Electrocortical activity and indices of antioxidative capacity and lipid peroxidation did not change significantly. Methemoglobin was not detected. In conclusion, inhalation of NO (up to 60 ppm) lowered Pap without directly affecting CBF, electrocortical activity, and redox status in the pulmonary vessels. CBF, however, can indirectly be influenced by NO-mediated changes in PCO2·
The Role of α2-Antiplasmin in the Inhibition of Clot Lysis in Newborns and Adults
Authors: Ries M. , Klinge J. , Rauch R. , Keuper H. , Harms D.
Published: October 2009

The fibrinolytic system is involved in a wide variety of biological phenomena and differs physiologically in newborns compared to older children or adults. Newborn’s plasminogen differs from adult plasminogen in carbohydrate composition, cell binding and activation kinetics. The fetal plasminogen has an increased concentration of sialic acid similar to fetal fibrinogen. In a previously reported study on plasminogen activation kinetics, we demonstrated differences in the reaction kinetics between fetal plasmin and plasmin inhibitors as compared to the reaction between adult plasmin and inhibitors. Hitherto, there are no investigations on the role of α2-antiplasmin in the inhibition of clot lysis in newborns. We studied the contributions of purified α2-antiplasmin to the regulation of fibrin clot lysis by use of a microtiter clot lysis assay. The lysis time of clots without adding purified α2-antiplasmin correlated to the activator dose. When purified α2-antiplasmin was incorporated at final concentrations ranging from 10 to 40 μg/ml, strong dose-dependent inhibition resulting in a prolongation of 50% lysis time was observed. The inhibition in newborns at all α2-antiplasmin concentrations was less pronounced than that of the adults if 50% lysis time was < 55 min. If 50% lysis time was > 55 min, the prolongation of 50% lysis time was more pronounced in newborn than in adult plasma. The fact that we have less effects of α2-antiplasmin in newborn infants at short reaction times despite the lower plasminogen levels, is consistent with slower reaction kinetics between plasmin and α2-antiplasmin in newborns. These differences raise an explanation for the findings of Idell et al. [Am J Respir Crit Care Med 1994;149:767–775] in premature baboons with neonatal respiratory distress syndrome (RDS). The knowledge of different reaction kinetics between plasmin and α2-antiplasmin and the role of α2-antiplasmin in the inhibition of clot lysis in newborns can be helpful to elucidate the significance of the fetal fibrinolytic system in neonatal RDS and to establish treatment strategies for fîbrinolytic therapy of progressive RDS.
Possible Effects of Placental Leucine Aminopeptidase on the Regulation of Brain-Gut Hormones in the Fetoplacental Unit
Authors: Mizutani S. , Goto K. , Tsujimoto M. , Nakazato H. , Matsuzawa K. , Furuhashi Y. , Arii K. , Tomoda Y.
Published: October 2009

The hydrolysis of somatostatin by human placental subcellular fractions and pregnancy sera was studied in the presence of selective inhibitors and the antibody against pregnancy serum oxytocinase (placental leucine aminopeptidase; EC3.4.11.3) by measuring the released amino acids by high-performance liquid chromatography. We also studied the degradation of other brain-gut hormones, such as glucagon, growth hormone, growth hormone releasing factor, and insulin, in the human placenta and found that the human placenta degrades somatostatin, glucagon, and growth hormone releasing factor, but not insulin and growth hormone. The degradation velocity of somatostatin was ten times greater than that of growth hormone releasing factor in placental microsomal fractions. Our data suggest that the stimulatory control by growth hormone releasing factor is dominant in the fetal growth hormone secretion. Our data also identified the somatostatin-degrading protease in human placenta using placental leucine aminopeptidase. It is known that the mean somatostatin levels in the umbilical artery are about 2.5-fold higher than those in the umbilical vein. Our data on somatostatin levels in umbilical artery and vein of intrauterine growth retardation human fetuses showed that the ratio umbilical artery/vein is around 1. Since insulin is known to be the primary hormone regulating the ratio of fetal growth, our data suggest that the degradation of somatostatin in the placenta is decreased and that elongation of somatostatin effects may result in the inhibition of insulin secretion in the intrauterine growth retardation fetus.
Pulmonary Surfactant Dysfunction in Congenital Diaphragmatic Hernia: Experimental and Clinical Findings
Authors: Valls-i-Soler Adolf , Alfonso Luisa F. , Arnaiz Arantzazu , Alvarez Francisco J. , Tovar Juan A.
Published: October 2009

Experimental and clinical findings indicate immaturity of pulmonary surfactant in congenital diaphragmatic hernia (CDH). Lung histology has shown a decreased amount of lamellar bodies. A low lecithin/sphingomyelin ratio in the amniotic fluid, and decreased concentrations of surfactant protein A and disaturated phosphatidylcholine in the pulmonary tissue and the amniotic fluid have been reported. Furthermore, low compliance and high surface tension have also been found. Evidence of clinical and experimental findings of structural, biochemical and functional pulmonary immaturity in CDH is reviewed. Prenatal administration of corticosteroids to accelerate fetal pulmonary maturation, and the use of early surfactant therapy, should be further evaluated in the clinical management of CDH.
A Rat Model for Hypoxic-Ischemic Brain Damage in Very Premature Infants
Authors: Sheldon Ann , Chuai Jing , Ferriero Donna M.
Published: October 2009

We proposed that hypoxic-ischemic injury suffered on postnatal day 1 (P1) in the newborn rat would yield significant and reproducible brain injury simulating that seen in a midgestation human brain. The P1 pup was subjected to ipsilateral common carotid ligation followed by 3.5 h of 6% O2 and demonstrated consistent histological changes in the ipsilateral hemisphere. At P2 neuronal loss and edema were pronounced in cortex and caudate; edema subsequently declined by P3. Astrocytic and microglial reactivity were seen as early as 24 h after injury, and by P10 both were extensive in damaged areas. There was marked loss of white matter on the affected side. We have demonstrated a reproducible model of hypoxic-ischemic injury to the very immature brain that can be used to elucidate mechanisms of neuronal loss and periventricular leukomalacia.
Haemoglobin Is Inversely Related to Plasma Lactate and Heart Rate in the Newborn Piglet
Authors: Haaland Kirsti , Kofstad Johan , Apricena Fabio , Thoresen Marianne
Published: October 2009

It has been hypothesized that an increased level of plasma lactate (La), the product of anaerobic glycolysis, may identify infants with anaemia and early tissue hypoxia. In the newborn piglet, a frequently used model in experimental neonatology, there is a substantial decrease in haemoglobin (Hb) during the first days of life. We have investigated whether a low level of Hb is associated with an increased level of La in the newborn piglet. Arterial blood gas, Hb, glucose, La, and continuous blood pressure and heart rate (HR) recordings were obtained from 66 newborn piglets. In 4 additional piglets recordings were obtained before isovolemic anaemia, during isovolemic anaemia, and after retransfusion of packed red cells. A low concentration of Hb in the newborn piglet correlates with an increased level of La as well as with an increased HR. A reduction of Hb causes an increase in La and in HR. We hypothesize that increased La and increased HR are caused by mild hypoxia due to normal, low Hb levels in the apparently healthy, resting newborn piglet.
Prenatal Hypoxia Alters the Postnatal Development of β-Adrenoceptors in the Rat Myocardium
Authors: Roigas J. , Roigas C. , Heydeck D. , Papies B.
Published: October 2009

The effect of prenatal hypoxia on the development of the β-adrenoceptor during the ontogenesis of rats was investigated. It was shown that the offspring from hypoxic dams, in comparison with normoxic control animals, exhibited alterations of the density (Bmax) of the myocardial β-receptors and of the catecholamine levels in heart tissue during development. The results suggest that the β-adrenoceptor changes might be involved in the phenomenon of enhanced sensitivity of prenatal hypoxic animals to catecholamines in adult age.
Effects of Preweaning Sensorimotor Stimulation on Behavioral and Neuronal Development in Motor and Visual Cortex of the Rat
Authors: Pascual Rodrigo , Figueroa Héctor
Published: October 2009

The present study investigates the effects of early sensorimotor stimulation on behavioral and neuronal cytodifferentiation in motor and visual cortex of lactating rats. Seventy-two male and female Sprague-Dawley albino rats were systematically submitted to environmental stimulation during the early postnatal period (postnatal days 5–21). On postnatal day 22, four behavioral tests were performed (open field, narrow path crossing, hind limb support and ascending on a rope). In order to evaluate dynamic neuronal changes induced by sensorimotor enrichment, brains were stained through the Golgi-Cox-Sholl method. Morphometric studies were carried out in pyramidal neurons located in motor and visual cortical layers II and III, by measuring their basal dendritic length and branching. Further, wide cortical field studies were performed with the aim of evaluating the degree of development reached by clusters of pyramidal cells. The results indicate that sensorimotor stimulation carried out during the suckling period produced a significant increase in neuronal cytodifferentiation as observed in single cell studies. However, collective neuronal evaluations yielded less significant results. Consistently, rats exposed to enriched environments showed a better performance in behavioral adaptive responses.
Moderate Anticonvulsant Action of Baclofen Does Not Change during Development
Authors: Kubová Hana , Haugvicová Renata , Mareš Pavel
Published: October 2009

The possible anticonvulsant action of baclofen, a GABAb (γ-aminobutyric acid) receptor agonist, was studied using two types of motor seizures (minimal, clonic and generalized tonicoclonic) elicited by pentylenetetrazol in adult rats and rat pups, 7, 12, 18, and 25 days old. If baclofen was administered intraperitoneally (only in 12- and 25-day-old rats), no effect could be observed in 25-day-old animals. In 12-day-old rats, only the 12-mg/kg dose led to a prolongation of the generalized tonicoclonic seizure latency. Subcutaneous administration of baclofen (3, 6, or 12 mg/kg 30 min before subcutaneous pentylenetetrazol injection) led to a moderate action against the tonic phase of generalized tonicoclonic seizures: the tonic phase of hind limbs was significantly suppressed in all age groups, whereas total suppression of the tonic phase was only outlined. Minimal, i.e., clonic, seizures with preserved righting ability were not influenced by baclofen. The conclusion could be made that the anticonvulsant action of baclofen is dependent on the model of seizures used and that there is no change of baclofen action against pentylenetetrazol-induced seizures during postnatal development in rats.
Nitric Oxide and Endothelin 1 during Postnatal Life
Authors: Endo Akihiko , Shimada Masami , Ayusawa Mamoru , Minato Michiyoshi , Takada Masaaki , Takahashi Shigeru , Harada Kensuke , Masaoka Naoki , Sato Kazuo
Published: October 2009

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 ± 12.8,53.8 ± 14.2, and 38.3 ± 13.2 μmol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 ± 1.6, 1.1 ± 0.2, and 1.1 ± 0.2 × 106 μmol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.
Pulmonary Pathology in Surfactant-Treated Preterm Infants with Respiratory Distress Syndrome: An Autopsy Study
Authors: Toti Paolo , Buonocore Giuseppe , Rinaldi Giuseppe , Catella Anna M. , Bracci Rodolfo
Published: October 2009

The present study examines the histological features of the lungs of neonates who died of respiratory distress syndrome or related complications after surfactant therapy. Our aim was to determine whether these lungs showed any unusual histological findings. Complete autopsies were performed 6–12 h after death in 10 surfactant-treated preterm infants and in 30 infants who died before surfactant therapy was available. Representative paraffin sections of all pulmonary lobes, stained with haematoxylin and eosin, were examined microscopically. A few selected slides were also stained with periodic acid-Schiff, Vierhoff-van Gieson, and Mallory trichrome. Hyaline membrane disease and bronchopulmonary dysplasia were present in each group, although there was an increased incidence of intra-alveolar haemorrhage in surfactant-treated babies (in 8 of 10 surfactant-treated as compared with 7 of 30 untreated babies). Amongst those treated with surfactant, we observed the persistence of acute alveolar damage with unresolved hyaline membrane disease in 5 infants who died at the ages of 5, 6, 10, 12, and 13 days, respectively, and histological evidence of pneumocyte type 2 hyperplasia and dysplasia in 2 infants who died at 22 and 41 days of age, respectively. These observations reveal that surfactant-treated infants who fail to respond to therapy have continuing alveolar injury and an increased incidence of intra-alveolar haemorrhage. Since oxygen radicals can induce pneumocyte damage and necrosis and since free radicals provoke alveolar haemorrhage in animal models, we propose that the lesions we observed may stem from a lack, in some preterm babies, of specific mechanisms that detoxify oxygen radicals.