bluuebunny/crossref_metadata_2025 huggingface dataset:
Sudden Infant Death Syndrome and Inherited Disorders of Fatty Acid β-Oxidation
Authors: Harpey Jean-Paul , Charpentier Christiane , Paturneau-Jouas Marion
Published: September 2009

Evidence that inherited disorders of mitochondrial fatty acid β-oxidation can cause sudden infant death syndrome (SIDS) comes from case reports, systematic autopsy studies, and family studies. Family studies are important when no pediatric autopsy has been done, which is still frequent. After reviewing the fatty acid β-oxidation, and its pathophysiology, we present the results of our metabolic study on 189 siblings of SIDS victims, and on 84 ‘near-miss’ infants. We have found evidence for a disorder of fat oxidation in 28 (15%) infants in the first group, and in 14 (17%) infants in the second group. Diagnosing and treating such disorders early in infancy may prevent some cases of SIDS to occur.
Modulation of Neonatal Rat Myeloid Kinetics Resulting in Peripheral Neutrophilia by Single Pulse Administration of Rh Granulocyte-Macrophage Colony-Stimulating Factor and Rh Granulocyte Colony-Stimulating Factor
Authors: Cairo Mitchell S. , van de Ven Carmella , Mauss Deborah , Kommareddy Sumithra , Norris Karol , Sheikh Kahild , Modanlou Houchang
Published: September 2009

Rh granulocyte-macrophage (GM) colony-stimulating factor (CSF) and rh granulocyte (G) CSF have been demonstrated to induce proliferation and maturation of myeloid stem cells and release of mature polymorphonucleocytes (PMNs) from human and animal adult bone marrows. Unfortunately, reduced bone marrow progenitor cells, neutrophil storage pool (NSP) depletion and peripheral neutropenia are characteristic of human and animal newborn bone marrows. We investigated the effect of administering intraperitoneal rhGM-CSF and rhG-CSF to Sprague-Dawley newborn rats (< 36 h). Newborn rats treated with intraperitoneal CSF (3.0 μg/kg) demonstrated significant leukocytosis at 6 and 24 h: rhGM-CSF vs. control, WBC (103/mm3), at 6 h, 8.0 ± 0.5 vs. 4.3 ± 0.9 (p ≤ 0.003), and at 24 h, 7.7 ± 1.7 vs. 3.8 ± 0.2 (p≤ 0.008); rhG-CSF vs. control WBC (103/mm3) at 6 h, 6.6 ± 1.2 vs. 4.3 ± 0.1 (p ≤ 0.03), and at 24 h, 8.1 ± 0.2 vs. 3.75 ± 0.2 (p ≤ 0.003). The absolute neutrophil count was also significantly elevated at 6 h following intraperitoneal CSF (3.0 μg/kg): RhGM-CSF vs. control, 1,827 ± 25 vs. 379 ± 10 (p ≤ 0.001); rhG-CSF vs. control, 1,698 ± 40 vs. 371 ± 10.1 (p ≤ 0.001). Additionally, femurs were surgically removed and flushed with buffer and marrow neutrophil storage pool (NSP; PMN + band + Meta) determined following rhGM-CSF (3.0 μg/kg vs. control) at 6 h: NSP 5.2 ± 1.3 vs. 16 ± 2.4% (p < 0.001), suggesting an association with peripheral neutrophilia at 6 h and NSP egress from the bone marrow. The NSP after 30 h demonstrated no difference between CSF and control. Lastly, marrow neutrophil proliferative pool (Blasts + Pro + Myelo) were determined after intraperitoneal rhG-CSF and GM-CSF and found to be significantly increased 48 h after administration. We postulate that CSFs may promote early leukocytosis and neutrophilia in the newborn rat by inducing NSP egress from the bone marrow, but do not completely exhaust NSP reserves.
Ontogeny of Iron Uptake across Brush Border Membrane of Guinea Pig Duodenum and Its Autoradiographic Localisation
Authors: Debnam Edward S. , Srai Surit K.S. , Chowrimootoo George , Epstein Owen
Published: September 2009

Although the neonatal guinea pig has substantial body iron stores, the rate of duodenal iron absorption is greater than in the mature animal. Here we have used brush border membrane vesicles and biopsy tissue to examine the role of the brush border in changes in Fe2+ and Fe3+ uptake by the duodenum of newborn and adult guinea pigs. We conclude that the brush border membrane is unlikely to be an important site for developmental alterations in iron absorption. Autoradiographic analysis of Fe2+ uptake, however, implies that whilst only the upper villus cells of adult duodenal villi are involved in iron uptake, all enterocytes in the neonate display this function.
Influence of Gestational Age on Potential Difference Across Fetal Type II Alveolar Epithelium in Alveolar-Like Structures
Authors: Orser B. , Fedorko L. , Rafii B. , Post M. , O’Brodovich H.
Published: September 2009

The active transport of ions across fetal pulmonary epithelium results in lung fluid secretion. This study investigated the potential difference (PD) across fetal type II alveolar epithelium, one of the several epithelial cell types in the fetal lung. Aggregates of these cells in alveolar-like structures (ALS) underwent microelectrode impalement to determine the effect of gestational age, and drugs on transcellular PD. In 6 ALS, the intraluminal position of the electrode was confirmed by fluorescent imaging after iontophoretic injection of Lucifer Yellow VS dye. The average PD recorded from the lumens of ALS harvested from 20-day fetal rats was 11.8 ± (SE) 0.48 mV (lumen-negative; n = 164). Exposure to ouabain 10––3M significantly reduced PD from control values of 12.3 ± (SE) 0.87 to 8.1 ± (SE) 0.95 mV (p < 0.01, n = 107) in ALS obtained from 20-day fetal rats. Terbutaline 10––3M and furosemide 10––3M did not influence PD. Cells obtained from fetuses near term showed a significant reduction in PD. ALS from 18-day (n = 53), 20-day (n = 164) and 22-day (n = 56) fetuses measured 13.5 ± 0.62, 11.8 ± 0.48 and 9.3 ± 0.49 mV, respectively (p < 0.05 day 18 vs. day 22). These results demonstrate that fetal type II cells grown in organotypic culture maintain a larger transcellular electrical gradient than previously reported. PD decreases with increasing gestational age and can be reduced by the Na-K ATPase inhibitor ouabain.
Lipase and Pepsin Activities in the Stomach Mucosa of the Suckling Dog
Authors: Kirk Charlotte L. , Iverson Sara J. , Hamosh Margit
Published: September 2009

The origin of preduodenal lipases was investigated in the suckling dog. In this species, gastric lipase is the main (or only) preduodenal lipase (activity range 1.03–8.32 U/mg protein), lingual-lipase activity being absent or amounting to traces only (0.77–2.3 mU/mg tissue). The localization of lipase activity in the stomach was mapped and compared to that of pepsin. The data show that the highest lipase activity was found in biopsy specimens of gastric mucosa from the cardia area (5.32 ± 1.29–8.32 ± 0.93 U/mg protein), and the lowest in the antrum (1.03 ± 0.16–1.94 ± 0.43 U/mg protein). Activity was also significantly higher in the mucosa along the greater rather than the lesser curvature of the stomach. Pepsin activity was highest in the cardia and gastric body areas (26.2 ± 0.89–89 ± 23.61 and 26.83 ± 15.98–69.51 ± 9.82, respectively). Contrary to lipase activity, considerable pepsin activity was present in the antrum (18.17 ± 4.12–23.07 ± 5.60 U/mg protein). No difference in pepsin activities was found in the greater as compared to the lesser curvature. The data show similar origin and tissue distribution of gastric digestive enzymes in the suckling dog and human infant. The role of the newborn dog as an animal model for fat digestion in the human infant is discussed.
Postnatal Development of Mouse Alcohol Dehydrogenases: Agarose Isoelectric Focusing Analyses of the Liver, Kidney, Stomach and Ocular Isozymes
Authors: Rout Ujjwal K. , Holmes Roger S.
Published: September 2009

The postnatal development of alcohol dehydrogenase (ADH) isozymes was studied in liver, kidney, stomach and eye tissues of C57BL/6J inbred male mice using agarose isoelectric focusing and histochemical methods. Development profiles were tissue specific, with adult patterns being attained by 30 days in the liver and stomach, and by 42 days in the kidneys. Ocular ADH-C2 increased in activity at the end of the first week, corresponding to the time of eye opening in the neonate.
Effects of Chronic Hypoxia during Maturation on the Negative Chronotropic Effect of [H+] on the Rabbit Sino-Atrial Node
Authors: Posner Philip , Baker Stephen P. , Epstein Michael L. , Macintosh Brian R. , Buss Daryl D.
Published: September 2009

Previous studies in our laboratory have shown an effect of 12 weeks of hypoxia on the electrophysiology of the heart. This study was designed to determine the effects of hypoxia for shorter periods (1,2,3 and 6 weeks) on the neonatal heart as well as the chronotropic effects of [H+] on sino-atrial automaticity. Rabbits (2 days of age) were raised for 1, 2, 3 or 6 weeks in either a normal or hypoxic environment. At the end of 1, 2, 3 or 6 weeks, they were killed and studied using an isolated sino-atrial tissue preparation and standard microelectrode techniques. Measurements of hematocrit, ventricular weight and ventricular total protein were made. Right ventricular hypertrophy appeared at 2 and 3 weeks in the hypoxic hearts. There was no difference in left ventricular weight or total protein between normal and hypoxic groups over the time studied. Both the basal and maximal (isoproterenol stimulated) spontaneous rates decreased with age. The baseline and maximal rates from hypoxic rabbits were significantly less than those from normal rabbits at 3 and 6 weeks (p < 0.05). The net negative chronotropic effect of elevated [H+] was more pronounced in the hypoxic than the normal preparations at 3 and 6 weeks. In summary, neonates raised in hypoxia for as short a period as 3 weeks show right ventricular hypertrophy and a decrease in sino-atrial automaticity. The net negative chronotropic effect of [H+] is enhanced with development and chronic hypoxia.
The High Lectin-Binding Capacity of Human Secretory IgA Protects Nonspecifically Mucosae against Environmental Antigens
Authors: Davin J.-C. , Senterre J. , Mahieu P.R.
Published: September 2009

The anti-infectious role of human milk may be, at least partly, ascribed to its content in secretory IgA. As lectins are present in various infectious antigens, the binding of different types of IgA to three lectins (concanavalin A, peanut agglutinin, wheat germ agglutinin) was studied by Elisa. The specificity of those bindings was assessed by inhibitory experiments performed with the corresponding oligosaccharides. The following were found for the three lectins: (1) the lectin-binding capacity of colostrum secretory IgA was markedly greater than that of normal plasma IgAl (p < 0.001); (2) the lectin-binding capacity of polymeric IgAl was greater than that of monomeric IgAl (p < 0.001). This property of mucosal IgA may be responsible of a nonimmune opsonization able to prevent the early step of some infectious mucosal diseases, i.e. the attachment of bacteria to epithelial cells by lectin-like bonds and also the penetration into the body of some antigens able to favor the development of allergy. Milk mucosal IgA, present in significant amounts in human colostrum and mature milk – but not in infant formulas – may therefore play an important polyvalent protective role in newborns.
CO2-Sensitivity in Newborn and Young Infants Tested by the Rebreathing Method
Authors: Katz-Salamon M.-S. , Hertzberg T. , Lagercrantz H.
Published: September 2009

The rebreathing method in newborn and young infants was tested with regard to the effects of increasing levels of CO2 on the behavioral state and to the influence of facial stimulation caused by the use of a face mask and pneumotachograph on the breathing pattern. Successive increases in inspired CO2 levels from 3 to 8.5% did not change the behavioral state. The application or removal of a face mask, with or without an attached pneumotachograph, caused an immediate disruption in the breathing pattern which lasted 10–40 s. Thereafter, breathing stabilized. When only the face mask was used, the increases in minute ventilation, tidal volume and cycle duration of 7, 13 and 5 %, respectively, were transient and lasted for 40–50 breaths. The breathing then returned to control levels. In contrast, breathing through the face mask connected to the pneumotachograph caused a long-lasting increase in ventilation (12%) due to the retention of CO2 in the spirometric circuit. We conclude that the inhalation of a continuously increasing mixture of 3–8.5% CO2 in O2 did not influence the behavioral state and that the effect of face mask on breathing pattern was transient.
Strain Differences in Mouse Brain Weight Gain and Spatial-Location Scores during Postnatal Development
Authors: Epstein Herman T. , Kaufman Martin , Saperstein Andrea , Frank Douglas , Huang Steven
Published: September 2009

Brain weight and performance on a spatial-location test were measured from birth to weaning on mouse strains CDl, Balb/c, and their F1 cross. For CD1, onsets of both the last rapid-brain-growth stage and nonzero scores on the spatial-location test were around age 17 days; asymptotes of both were reached about age 23 days. Balb/c and F1 had at least 5-to 6-day delays of both onsets and asymptotes. For the strains studied, onset of nonzero performance on the spatial-location test may be a provisional indicator of onset of significant and rapid brain growth after age 15 days. The delayed Fl brain growth stage could indicate that control of brain growth about age 20 days resides in an inhibitory factor present in Balb/c but not in CDl.
Clinical and Physiological Responses to Prolonged Nasogastric Administration of Doxapram for Apnea of Prematurity
Authors: Tay-Uyboco Jean , Kwiatkowski Kim , Cates Donald B. , Seifert Blair , Hasan Shabih U. , Rigatto Henrique
Published: September 2009

We hypothesized that enteral doxapram would effectively treat apnea of prematurity without the appearance of major side effects. Of 16 infants, 10 (BW 1,520 ± 102 g) received doxapram alone and 6 (BW 1,020 ± 35 g) received doxapram plus theophylline. Apneas decreased from 16.7 ± 1.9 to 2.1 ± 0.6 in infants receiving doxapram alone, and from 38.2 ± 4.4 to 7.9 ± 2.2 apneas/24 h in those receiving doxapram plus theophylline. This was associated with an increase in alveolar ventilation, a shift of the ventilatory response to CO2 to the left, and no change in the immediate ventilatory response to 100% oxygen. Side effects included premature teeth buds corresponding to the lower central incisors, prevalence of occult blood in stool and necrotizing enterocolitis. The findings suggest that doxapram effectively controls apnea when given enterally, but should be used cautiously because of potentially harmful side effects.
Hemodynamic Effects of Conventional and High Frequency Oscillatory Ventilation in Normal and Septic Piglets
Authors: Osiovich Horacio C. , Suguihara Cleide , Goldberg Ronald N. , Hehre Dorothy , Martinez Octavio , Bancalari Eduardo
Published: September 2009

The cardiovascular effects of high frequency oscillation (HFO) and conventional ventilation (CMV) were evaluated in 10 piglets prior to and during an infusion of group B streptococci (GBS). Animals were randomized to begin ventilation with either HFO or CMV. Arterial blood gases, cardiac output (CO), and pulmonary artery (Ppa), pulmonary wedge (Ppw) and arterial blood pressures were measured. These values were recorded at a mean airway pressure (MAP) of 2 cm H2O for both modes of ventilation after which a continuous infusion of GBS (4 × 107 CFU/kg/min) was begun. MAP was increased in both ventilators in the following sequence: 4, 8 and 12 cm H2O. Prior to GBS infusion, HFO was associated with small but significant changes in hemodynamic parameters when compared to CMV for the following: Ppa (15 ± 4 vs. 13 ± 4.0 mm Hg; p < 0.03), Ppw (3 ± 1 vs. 2 ± 1 mm Hg; p < 0.02), and CO (0.24 ± 0.08 vs. 0.25 ± 0.09 1/min/kg; p < 0.05). Similar statistically significant increases in Ppa (p < 0.005) and Ppw (p < 0.0001), and decrease in CO (p < 0.007) were present during GBS infusion when animals were ventilated with HFO, irrespective of the MAP used. Our results suggest that the use of HFO in both normal piglets and those receiving an infusion of GBS results in mild but consistent impairment in cardiovascular function compared to CMV. In summary, these data demonstrate that HFO has no beneficial effect compared to CMV at similar MAP in the management of the septic piglet model and may in fact further compromise the animal’s hemodynamic status.
Glycogen and Enzymes of Glycogen Metabolism in Rat Embryos and Fetal Organs
Authors: Gutierrez-Correa Jose , Hod Moshe , Passoneau Janet V. , Freinkel Norbert
Published: September 2009

Glycogen content and the enzymes of glycogen metabolism have been measured in the postimplantation rat embryo over a period ranging from 9.5 to 18.5 days of gestation. The earliest periods studied were at days 9.5 and 10.5 of gestation, when the yolk sac becomes vascularized and heart beat is first established. The next intervals were at days 10.5–11.5 when vascular connections via the allantoic placenta are formed. At 14.5 and 18.5 days of development, 4 entire organs were analyzed; heart, liver, kidney and brain. The metabolic apparatus of glycogen metabolism was concentrated in the embryo at 10.5 days, then the heart region, and in the heart itself at later stages.
Effect of Maternal Administration of Thyrotropin-Releasing Hormone or DN1417 on Functional and Morphologic Fetal Rabbit Lung Maturation and Duration of Survival after Premature Delivery
Authors: Devaskar Uday P. , deMello Daphne E. , Ackerman Julie
Published: September 2009

Though maternal treatment with thyrotropin-releasing hormone (TRH) for prevention of hyaline membrane disease has been utilized, precise mechanisms of TRH in accelerating fetal lung maturation remain unclear. We studied the effect of maternally administered TRH or DN1417 (an analog of TRH) on functional and morphologic fetal rabbit lung maturation and the duration of survival after premature delivery. Because DN1417 retains the neurotransmitter but not the neuroendocrine effects of TRH, this study enables us to determine which of these effects was responsible for enhancement of lung maturation. TRH or DN1417 (0.2 mg/kg/dose) or saline was injected intravenously into New Zealand White rabbit does 48, 36, 24, 12 and 2 h prior to sacrifice on day 27 of gestation. Functional pulmonary maturity was assessed by pressure-volume hysteresis, and morphologic maturity was assessed by histologic techniques. Maternal administration of TRH or DN1417 enhanced both functional and morphologic fetal lung maturation as well as the duration of neonatal survival after premature delivery. We propose that the effect of TRH in fetal lung maturation is due to neurotransmitter rather than neuroendocrine effects.
Apolipoprotein A-I-Containing Lipoproteins in Human Umbilical Cord Blood
Authors: Barkia Ahmed , Thiemann Elisabeth , Czekelius Peter , Wiegel Andreas , Leroy Arnaud , Fruchart Jean-Charles , Steinmetz Armin
Published: September 2009

Lipids, apolipoproteins, lipoproteins, as well as lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) or apo A-I but no apo A-II (Lp A-I), proapolipoprotein (proapo) A-I and the activity of lecithin:cholesterol acyltransferase (LCAT), were investigated in umbilical cord sera of 67 term human neonates (30 females and 37 males). Lp A-I and Lp A-LA-II were present in umbilical cord sera with levels of 0.26 ± 0.1 and 0.33 ± 0.15 g/l, respectively. Furthermore, the absolute amount of proapo A-I was lower in cord blood than in adult plasma, but in view of the lower apo A-I levels in umbilical cord sera it comprised 10.48 ± 3.86% of total apo A-I and was thus significantly higher than in adult plasma (7.1 ± 0.9%). Proapo A-I was highly correlated with HDL cholesterol and apo A-I. Total serum LCAT activity was about 50% of adult plasma and was highly correlated with Lp A-I, but not with Lp A-I:A-II. We conclude that human umbilical cord serum contains both Lp A-I and Lp A-I:A-II particles and that the LCAT activity is predominantly related with the Lp A-I subfraction. The higher percentage in umbilical cord sera of proapo A-I may indicate a higher turnover of apo A-I or a lower activity of the proapo A-I cleaving enzyme which is still not identified.
Insulin-Like Growth Factor I and II Gene Expression in Balb/C Mouse Liver during Postnatal Development
Authors: Singh Juliet S. , Rall Leslie B. , Styne Dennis M.
Published: September 2009

We studied the developmental shift from IGF-II to IGF-I mRNA synthesis in Balb/C mouse liver. IGF-I mRNA levels were low at birth, increased with age to peak at weaning, and IGF-I gene expression again increased during puberty. IGF-II expression was high during early postnatal development, but became nondetectable at weaning. Thus in early life there is a reciprocal relationship of rising IGF-I and falling IGF-II mRNA. Northern analysis revealed four IGF-I mRNA transcripts ranging from 1.1–7.0 kb, with the 1.1 kb being the most prominent. Five IGF-II transcripts ranging from 1.7–4.0 kb were found, with the 4,0 kb being the most prominent. The pattern of Serum IGF-I and IGF-II values paralleled liver IGF-I and IGF-II mRNA levels.
Sn-Protoporphyrin plus Photoirradiation Induces Lipid Peroxidation in vivo and in vitro in Nonjaundiced Gunn Rats
Authors: Mimura S. , Nagae H. , Keino H. , Watanabe K. , Kashiwamata S.
Published: September 2009

Lipid peroxidation induced by Sn-protoporphyrin (SnPP) plus photoirradiation was investigated in vivo and in vitro using nonjaundiced Gunn rats. Membrane lipids from young adult rat brain were peroxidized by SnPP plus photoirradiation depending on the SnPP concentration and photoirradiance. Similarly, coadministration of SnPP and photoirradiation to suckling rats increased lipid peroxides in the whole blood and was found lethal. The influence of the wavelength distribution of light sources was also examined by using blue-white and green fluorescent lights. The photodynamic effect by green light irradiation whose energy distribution had no overlap with the Soret band of SnPP was about half of that produced by blue-white light with regard to the membrane peroxidation and the lethal effect on neonatal rats. We therefore conclude that the combination of SnPP and photoirradiation is a potentially hazardous treatment of neonatal jaundice.
Metallothionein Messenger RNA Levels in the Macular Mutant Mouse: An Animal Model of Menkes’ Kinky-Hair Disease
Authors: Shiraishi Noriyuki , Taguchi Tetsuya , Kinebuchi Hideo
Published: September 2009

Levels of metallothionein-1 (MT-1) messenger RNA (mRNA) in various tissues from normal and macular mutant mice at different stages of development (17 days of gestation, 1-, 3-, 7- and 14-day-old) were determined by Northern blot analysis. Renal MT-1 mRNA levels in mutant mice were slightly elevated at 3 stages compared to normal mice, with the exception of mutant fetus and 3-day-old mutant mice. Intestinal MT-1 mRNA levels in mutant mice were elevated at 3 stages compared to normal mice with the exception of mutant fetus and 3-day-old mutant mice. Hepatic MT-1 mRNA levels in mutant fetus and 1-day-old mutant mice were approximately the same compared to normal mice. In 3- and 7-day-old mutant mice, hepatic MT-1 mRNA levels were depressed and in 14-day-old mutant mice, they were increased compared to normal mice. Brain MT-1 mRNA could not be detected in normal and mutant mice at the 4 stages with the exception of 14-day-old mice. MT-1 mRNA in 14-day-old mice was detected and the level of that in mutant mice was slightly elevated compared to normal mice. After injection of Cu, MT-1 mRNA levels in kidney, liver and intestine were determined. The injection of Cu increased the level of MT-1 mRNA in the tissues of normal and mutant mice compared to control (saline-injected) mice. Significant differences in MT-1 mRNA levels in the tissues of both Cu-injected mice were not observed.
Febrile Convulsions Induced by Microwaves and the Alteration in Behavior of Albino Mouse OF1
Authors: Carratalá F. , Moya M.
Published: September 2009

We studied the effects of microwave (2,440 MHz) induced febrile convulsions (FCs) on the behavior and development of 31 albino mice (OF1 strain), between 25 and 30 days old, in comparison with a group of 33 animals from the same litters. Previously a string test was adapted to measure the neurodevelopment of mice in the first 6 months of life with 82 animals of the same characteristics. The animals submitted to convulsions (fit temperature = 39.2 ± 0.96 °C) showed normal growth, in fact they obtained better results in the test than the control mice (2-way ANOVA, p < 0.01). FCs have no negative influence on the normal behavior of the mouse.
Spectral Edge Frequency of the EEG in Healthy Neonates and Variation with Behavioural State
Authors: Bell Angela H. , McClure B.G. , McCullagh P.J. , McClelland R.J.
Published: September 2009

Spectral edge frequency (SEF) of the EEG was studied in 51 healthy neonates to assess its value as a measure of cerebral maturation. SEF was calculated as the frequency below which 95% of the power in the power spectrum resides. Summated SEF (sSEF) of 4 EEG channels correlated significantly with gestational age (r = 0.83).sSEF varied with behavioural state and with EEG derivation. Intra- and interindividual variability were both greater in preterm compared to term babies. We conclude that SEF is a useful measure of cerebral maturation in the newborn and may have a role in studying stressed newborns.
Plasma and Erythrocyte Amino Acids in Mother and Fetus
Authors: Cetin Irene , Hirst Kathryn , Corbetta Carlo , Sereni Lucia Piceni , Marconi Anna Maria , Zerbe Gary O.
Published: September 2009

Plasma (P) and whole blood (WB) amino acid concentrations were measured in arterial and venous blood of 9 mothers and their fetuses at elective cesarean section and compared to values obtained in 5 normal nonpregnant women. Erythrocyte (E) amino acid concentrations were calculated from P and WB concentrations. E/P ratios were significantly greater than 1.0 in all groups studied. Alanine, glycine, and serine presented E/P ratios significantly higher in pregnant women than in control nonpregnant women. Fetuses presented significantly lower E/P ratios for lysine than pregnant and nonpregnant women. Uterine arteriovenous amino acid differences were not significantly different from zero in both plasma and erythrocytes. Umbilical venous-arterial differences were significantly positive for most essential amino acids in plasma, whereas they were not significantly different from zero in erythrocytes. This finding suggests that erythrocytes do not play a major role in the transfer of amino acids from the placenta to the fetus.
Control of Adenylate Cyclase Activity in Developing Rat Heart and Liver: Effects of Prenatal Exposure to Terbutaline or Dexamethasone
Authors: Navarro Herman A. , Kudlacz Elizabeth M. , Slotkin Theodore A.
Published: September 2009

Adrenergic stimulation and glucocorticoids have been hypothesized to control the development of β-adrenergic receptors and responsiveness. In the current study, rats were exposed to a β-agonist (terbutaline) or a glucocorticoid (dexamethasone) during late gestation, and the development of adenylate cyclase activity and β-receptor binding was evaluated in membranes prepared from the heart and liver. In control heart, basal, isoproterenol-stimulated and forskolin-stimulated adenylate cyclase showed distinct developmental spikes of activity that were unrelated to changes in receptor binding sites, but that instead corresponded temporally to periods of sympathetic neuronal activation. Prenatal exposure to terbutaline initially enhanced all three enzymatic measures in the immediate postpartum period but delayed the appearance and exaggerated the magnitude of the subsequent peaks; again, these changes occurred without specific relation to effects on receptor binding. Dexamethasone produced a similar shift in the peaks of cardiac enzyme activity. In the liver, where β-adrenergic receptors and responsiveness decline after birth, terbutaline and dexamethasone had much smaller effects on adenylate cyclase. These results suggest that β-adrenergic stimulation serves as a trophic factor controlling the ontogenetic rise of adenylate cyclase activity; regulation involves the level of the enzyme itself rather than changes in receptor binding capabilities or receptor-specific linkages. Consequently, prenatal administration of β-agonists or glucocorticoids can cause long-term alterations in enzyme activity and responsiveness.
Characteristics and Functional Properties of Red Cells during the First Days of Life
Authors: Buonocore Giuseppe , Berni Silvia , Gioia Dino , Bracci Rodolfo
Published: September 2009

In order to evaluate postnatal red blood cell (RBC) properties and whole-blood rheology, 36 healthy full-term newborn infants were tested twice (cord blood, 4th-day blood) for whole-blood flow rate, hematocrit, hemoglobin (Hb), RBC count, mean corpuscular volume, mean corpuscular Hb and its concentration, white blood cell and platelet count, plasma fibrinogen, erythrocyte glucose-6-phosphate dehydrogenase, glutathione peroxidase (GSH-Px), glutathione reductase, catalase and superoxide dismutase. Another 38 healthy full-term newborns were tested twice for separation of erythrocytes into fractions of different density. Healthy adults were taken as control. The results showed a decreased whole-blood flow rate in blood drawn on the 4th day with respect to cord blood. A multivariate analysis with flow rate as dependent variable demonstrated a significant positive correlation with GSH-Px on the 4th day. The assays of RBC densities showed a significant increase in the first 4 days.
Different Patterns of Pulmonary Sequelae after Hyaline Membrane Disease: Heterogeneity of Bronchopulmonary Dysplasia?
Authors: Van Lierde Stefaan , Cornelis Ann , Devlieger Hugo , Moerman Philippe , Lauweryns Joseph , Eggermont Ephrem
Published: September 2009

In an autopsy study of 37 infants who suffered from hyaline membrane disease (HMD), two distinct patterns of pulmonary lesions could be defined. One pattern, characterized by marked interstitial fibrosis in the absence of airway abnormalities, was labelled Ê»interstitial-type’ histology. A second type, labelled Ê»bronchiolar-type’ histology, showed marked airway lesions and alveolar emphysema. Nine patients of each type were analysed. Nineteen other patients had a Ê»mixed-type’ histology and were not further studied. Retrospectively, the clinical and radiological characteristics of both series were analysed. No differences in birth weight, gestational age and initial radiological HMD grade could be demonstrated. The pulmonary function of the bronchiolar-type patients however was significantly worse at the onset, and these infants needed more oxygen and ventilatory support during the first 10 days of life. They all died from respiratory failure whereas 4 patients from the interstitial group had non-pulmonary fatalities. In the bronchiolar group chest X-rays showed atelectasis and pulmonary interstitial emphysema in the early stages, and hyperinflation with bullae and irregular streaky densities in the later. Patients in the interstitial group had no or minor emphysema with more homogeneously spread densities over both lungs. We conclude that both types of evolution represent two extremes of the bronchopulmonary dysplasia spectrum.
Severe Intrauterine Infection due to Capnocytophaga ochracea
Authors: Mayatepek E. , Zilow E. , Pohl S.
Published: September 2009

A case of severe neonatal sepsis due to intrauterine infection with Capnocytophagaochracea, complicated by hypotension, renal failure and disseminated intravascular coagulation, is reported. The role of Capnocytophaga as an organism of increasing importance in intrauterine and peripartum infections is discussed.
Lipids, Lipoproteins and Apolipoproteins AI AII, B, CII, CIII and E in Newborns
Authors: Averna M.R. , Barbagallo C.M. , Di Paola G. , Labisi M. , Pinna G. , Marino G. , Dimita U. , Notarbartolo A.
Published: September 2009

In this study lipid and apolipoprotein patterns were investigated at birth and compared with those of adults. In cord sera, cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were 38.2, 46.2, 50.5, and 31.9%, respectively, of adult values. Apolipoprotein AII, B and CIII were 48.6, 30.6 and 44.5% of adult values, while apo AI, apo CII and apo E showed values approaching those of adults (63.4, 73.3 and 89.7%, respectively). Also cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios were lower in newborns. In cord sera, lipids were correlated with various apolipoproteins in a surprisingly different way from adult sera. HDL cholesterol was not inversely correlated with triglycerides, and showed a highly positive correlation with apo E, apo CII and apo CIII, which did not correlate with HDL cholesterol in adults. These data supported the presence of significant differences in plasma concentrations and composition of lipoproteins at birth. Therefore HDL, apo CII, and apo E seem to play a different and more important metabolic role in neonatal lipid metabolism.
Effect of Fasting on Uteroplacental Amino Acid Metabolism in the Pregnant Sheep
Authors: Liechty Edward A. , Kelley Jeffry , Lemons James A.
Published: September 2009

In the fed state, the net utilization of most amino acids by the ovine uteroplacental unit (defined as uterine uptake minus umbilical uptake) is zero. This study was to determine if this is true for the fasted pregnant ewe also, when uteroplacental glucose uptake is diminished. Glucose and amino acid concentrations were determined in 9 pregnant ewes across the uterine and umbilical circulations. Uterine and umbilical blood flows were determined by the steady state antipyrine diffusion method, and net uptakes across each circulation calculated by application of the Fick principle. Five amino acids were found to have a consistently greater uterine uptake than umbilical uptake. In addition, glutamate had a negative net umbilical uptake coupled with no net uterine uptake. Fasting resulted in an increase in the differences between the respective uptakes for all five amino acids. No additional amino acids were found to have disparate uptakes than were seen in the fed state. Umbilical glutamate uptake became less negative during fasting, but the difference between the uterine and umbilical circulations remained unchanged, as the uterine circulation took up glutamate during fasting. The umbilical circulation took up α-ketoisocaproate (0.626 ± 0.18, fed), and the uptake was increased during fasting (1.8 ± 0.6). These findings suggest that the branched chain amino acids and glutamine are utilized by the ovine uteroplacenta to a greater degree than are most other amino acids, and at increased rates during fasting of the ewe. These amino acids, through deamination, may be the source of uteroplacental ammonia production, as well as serving as an energy substrate when glucose supply is limited.
A Morphometric Study of Lung Maturation in the Adrenocorticotrophin-Infused Fetal Lamb
Authors: Kendall J.Z. , Rivera-Alcina M.E. , Plopper C.G. , Weir A.J. , Randall G.C. , Saldana-Gautier L.
Published: September 2009

Adrenocorticotrophin (ACTH) effects on lung development were studied in sheep. ACTH was infused into 10 fetal lambs at 129 days of gestation at a rate of 29, 110 or 250 μg/day for 72 h, a time course which was independent of the mechanical and hormonal forces associated with labor. Lungs were compared with those of normal fetuses at term (day 147). ACTH accelerates maturation of components of lung structure toward term values. Different components of cytodifferentiation of the type II alveolar cell showed different levels of sensitivity. The degree of acceleration, not the nature of the changes, was influenced by dose.
Relationship between Newborn and Maternal Iron Status and Haematological Indices
Authors: Lao T.T. , Loong E.P.L·. , Chin R.K.H. , Lam C.W. K. , Lam Y.M.
Published: September 2009

The haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin, haematocrit, serum iron and total iron binding capacity, and serum ferritin concentrations in umbilical cord blood samples taken from 96 appropriate-for-gestational age infants delivered at term were measured and compared to the respective maternal values measured at 36 weeks’ gestation. All the values were higher in cord blood. Only maternal mean corpuscular volume and mean corpuscular haemoglobin were correlated with cord serum iron. Cord blood haematological indices were not correlated with either gestation at delivery or birth weight. However, newborn serum ferritin was positively correlated with gestation at delivery, while the maternaknewborn ferritin ratio was inversely correlated with gestation and birth weight. The results suggest that maternal haematological and iron indices are not predictive of the haemoglobin or iron status of the newborn, and that the fetus continues to take up iron from the mother until delivery.
Influence of Albumin-Bound Bilirubin on the Antibody-Dependent Cellular Cytotoxicity of Human Cells in vitro
Authors: Meisel P. , Jahr H.
Published: September 2009

In neonatal hyperbilirubinaemia the distribution of unconjugated bilirubin (BR) between albumin and cellular binding determines its toxicity. The relationship between the ratio of BR/albumin and the impairment of cellular functions was studied employing a system of antibody-dependent cellular cytotoxicity (ADCC) with erythrocytes as target cells. The cytotoxic activity of peripheral blood monocytes, lymphocytes and granulocytes is inhibited in a concentration-related manner depending on the molar ratio BR/albumin. The occupation of albumin binding sites by BR is related to the extent of inhibition of ADCC activity suggesting that there is a competition between albumin and cellular binding sites for free bilirubin. This competition is governed by the respective affinity and concentration of the binding sites. Bilirubin binding to the cellular (silent) membrane receptors leads to the chain of events resulting in impairment of cellular functions, i.e. ADCC.
Plasma Catecholamine Response to Fetal Hypoxemia Is Not Potentiated by Naloxone
Authors: Lewis Alan B. , Sadeghi Mahvash
Published: September 2009

The interaction between the plasma catecholamine response to hypoxemia and endogenous opiate receptor blockade was investigated in 9 fetal lambs. The animals were randomly assigned to receive either normal saline (control group 1) or two doses of naloxone (group 2 = 0.5 mg/kg; group 3 = 1.0 mg/kg) by bolus injection followed by continuous infusion. Arterial PO2 decreased from 21 to 12 Torr and remained < 14 Torr for 1 h. Arterial pH declined from 7.40 to a nadir of 7.32 at 1 h. Mean plasma catecholamine concentrations rose promptly from a baseline of 524–546 pg/ml for norepinephrine (NE) and 156–235 pg/ml for epinephrine (E) to reach a peak at 15 min (NE = 2,476–3,276, p < 0.01; E = 1,856–4,065 pg/ ml, p < 0.01) and remained elevated thereafter. Neither dose of naloxone significantly altered plasma NE or E concentrations. Therefore, we conclude that endogenous opiates do not modulate the sympathoadrenal response to moderately long periods of hypoxemia unaccompanied by acidemia.
Ascorbic Acid Concentration in Amniotic Fluid in Late Pregnancy
Authors: Barrett Bridget , Gunter Elaine , Jenkins James , Wang Marian
Published: September 2009

Amniotic fluid and venous blood specimens were obtained from 34 pregnant women and analyzed for the ascorbic acid concentration. The mean amniotic ascorbic acid concentration of smoking pregnant women was less than 50% of that of non-smoking women. Pregnant women who smoked had a significantly lower serum and amniotic fluid ascorbic acid concentration than those who did not smoke. No differences were observed between the groups with or without premature rupture of the fetal membrane. The results suggest that ascorbic acid in the amniotic fluid reflects the ascorbic acid status in the blood of pregnant women and smoking had a greater effect in decreasing the ascorbic acid concentration in amniotic fluid than in serum.
Human Umbilical Cord as a Possible Source of Progesterone
Authors: Gunasegaram R. , Peh K.L. , Loganath A. , Chew P.C.T. , Ratnam S.S.
Published: September 2009

Homogenates of human term umbilical cord were incubated with 7n-3H-pregnenolone. Using a reverse-isotope dilution technique, 3H-progesterone was isolated and characterized. The extent of enzymic conversion ranged from 2.5 to 55.4%. The results indicate that the cord can be a source of progesterone during human pregnancy.
Plasma Protein Binding of Theophylline during Development in the Rabbit
Authors: Aramayona J.J. , Bonati M. , Bortolotti A. , Castelli D. , Gaspari F. , Lucchini G.
Published: September 2009

The plasma protein binding profile of theophylline was investigated in the rabbit during the perinatal and developmental period. The roles of unbound plasma theophylline fraction (THu), albumin, nonesterified fatty acids (NEFA) and plasma bilirubin levels were analyzed. Plasma total protein and albumin levels doubled with age from the 1st day of life to maturity (from 3.1 to 5.3 and 1.6 to 3.7 g/l, respectively). THU, NEFA and bilirubin levels were inversely related to age, and decreased from 81 to 37%, 2,136 to 239 μEq/l and 2.4 to 0.20 mg/dl, respectively. A linear correlation was shown between THu and albumin, NEFA, and bilirubin plasma concentrations. Stepwise multiple linear regression analysis, including albumin, NEFA and bilirubin values as independent variables, identified NEFA as the variable explaining most of the variability in plasma protein binding of theophylline. Findings support the need for careful interpretation (with a view to therapeutic utilization) of estimates of plasma protein unbound fraction of a drug during development. This fact highlights the importance of considering not only protein but NEFA concentrations too.
Clinical Application of Exhaled Breath Condensate Analysis in Asthma: Prediction of FEV1 Improvement by Steroid Therapy
Authors: Matsunaga Kazuto , Ichikawa Tomohiro , Yanagisawa Satoru , Akamatsu Keiichirou , Koarai Akira , Hirano Tsunahiko , Sugiura Hisatoshi , Minakata Yoshiaki , Ichinose Masakazu
Published: September 2009

Background: Exhaled breath condensate (EBC) measurements have recently been reported to be useful for the detection of inflammatory molecules in the airways. However, the clinical relevance of EBC analysis in asthma therapy has not been determined yet. Objectives: To investigate whether EBC analysis has any potential for predicting the steroid response in asthmatics. Methods: Eighteen steroid-naive asthmatics were enrolled. EBC collection, spirometry and a methacholine challenge test were performed before and 12 weeks after inhaled steroid therapy. Exhaled IL-4, IL-17, RANTES, macrophage inflammatory protein (MIP)-1α, MIP-1β, IL-8, IFN-γ-inducible protein (IP)-10, TNF-α and TGF-β were simultaneously analyzed by a protein array, and the relationship between baseline molecule expression and steroid-mediated changes in forced expiratory volume in 1 s (FEV1) and airway responsiveness was investigated. Results: Steroid therapy improved FEV1 values and the methacholine threshold. Among the molecules examined, increased IL-4 and RANTES levels as well as decreased IP-10 levels at baseline were significantly correlated with an improvement in FEV1. By contrast, molecule levels were not related to changes in the responsiveness to methacholine. In addition, changes in FEV1 values were significantly associated with reductions in IL-4 and RANTES levels. Conclusions: EBC measurements of IL-4, RANTES and IP-10 might be useful for predicting the steroid-mediated FEV1 improvement in asthma.
Cardiovascular Aspects in Obstructive Sleep Apnea Syndrome – Molecular Issues, Hypoxia and Cytokine Profiles
Authors: Lavie Lena , Polotsky Vsevolod
Published: September 2009

Obstructive sleep apnea syndrome (OSAS), which is a highly prevalent breathing disorder in sleep, is an independent risk factor for cardiovascular morbidity and mortality. Results from clinical studies as well as animal models and cell culture studies utilizing intermittent hypoxia implicate oxidative stress and inflammation in the pathogenesis of OSAS. However, the underlying mechanisms are not entirely understood. Both oxidative stress and inflammation are major components in the initiation and development of endothelial dysfunction and consequently atherosclerosis. Yet, these fundamental mechanisms are associated with obesity and with components of the metabolic syndrome that also cluster with OSAS. Accumulated evidence indicates that inflammatory cytokines such as TNF-α that are under the control of nuclear factor κB actively participate in endothelial damage. The current review highlights some of the recent findings on oxidative stress and inflammation in OSAS with specific emphasis on the role of inflammatory pathway activation and expression of cytokines and their possible role in OSAS-related cardiovascular morbidity. In light of the new findings in the field of cytokines, their potential involvement in endothelial dysfunction and cardiovascular morbidity in OSAS is discussed.
Hemoglobin Level Variability: Anemia Management among Variability Groups
Authors: Gilbertson David T. , Peng Yi , Bradbury Brian , Ebben James P. , Collins Allan J.
Published: September 2009

Background/Aims: Hemoglobin level variability in hemodialysis patients is common, and has been associated with comorbidity, intercurrent illness, and mortality risk. We aimed to describe the influence of anemia management interventions (erythropoiesis-stimulating agents [ESAs], intravenous iron, and transfusions) on hemoglobin variability. Methods:We studied all Medicare primary payer hemodialysis patients who survived and had ESA claims in the first 6 months of 2004 (n = 159,720). Monthly hemoglobin values were categorized as low (<11 g/dl), intermediate (11–12.5 g/dl), and high (>12.5 g/dl). Variability groups were classified based on lowest and highest hemoglobin categories during a 6-month observation period. ESA, intravenous iron, and transfusion use were characterized by variability group. Results:Patients with consistently low or low and intermediate hemoglobin received the highest ESA doses and the most frequent transfusions, while patients with consistently or intermittently intermediate or high hemoglobin received lower ESA doses and fewer transfusions. Intravenous iron doses were highest initially for patients with consistently high hemoglobin; these doses subsequently declined. Iron doses were lowest for patients with consistently intermediate hemoglobin. Conclusions: Anemia management protocols describing coordinated administration of ESAs and iron may help to increase the number of patients achieving target hemoglobin levels.