bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrauterine Growth Retardation Due to Growth Hormone Deficiency in Rats
Authors: Nogami Haruo , Tachibana Toshiaki , Ishikawa Hiroshi
Published: October 2009

The effect of growth hormone (GH) on fetal growth was examined in the spontaneous dwarf rat (SDR) with the isolated GH deficiency. A 328-bp GH gene fragment containing the site of SDR mutation was amplified from fetal liver genomic DNA using PCR and digested with restriction enzyme SauI to distinguish the fetal genotype. When heterozygote (dr/+) males and females were crossed, a significant reduction in body weight of dr/dr fetuses was observed on days 20 and 21 (92 and 89% that of +/+ fetuses, respectively). Body weight reduction was also noticed on day 21 in dr/dr fetuses (80%) in comparison with that of dr/+ fetuses crossed from dr/dr females and dr/+ males. Unexpectedly, the body weight of dr/+ fetuses was found to be significantly less than that of +/+ fetuses on days 19 (94%) and 20 (97%), which reached the level of +/+ fetuses by day 21 of gestation. The fetal tail length was not affected by the GH status. These results provide direct evidence for the involvement of pituitary GH in the regulation of fetal body weight during late gestation, but not in fetal skeletal growth.
Brain Cell Membrane Na+,K+-ATPase Activity after Inhibition of Cerebral Nitric Oxide Synthase by Intravenous NG-Nitro-L-Arginine in Newborn Piglets
Authors: Groenendaal Floris , Mishra Om P. , McGowan Jane E. , Delivoria-Papadopoulos Maria
Published: October 2009

This study investigated the effects of in vivo inhibition of cerebral nitric oxide synthase by intravenous administration of NG-nitro-L-arginine (NNLA) on the cell membrane Na+,K+-ATPase activity in the cerebral cortex of newborn piglets. NNLA was administered intravenously to 22 piglets at doses of 5 mg/kg (n = 3), 25 (n = 3), 50 (n = 4), 75 (n = 4), and 100 mg/kg (n = 2). Control animals (n = 6) received normal saline only. 90 min after infusion the cerebrum was obtained. The cerebral nitric oxide synthase activity, determined by measuring the conversion of [3H]-L-arginine into [3H]-L-citrulline in the brain homogenate, decreased from 9.1 ± 2.0 pmol/mg protein/min in controls to 1.7 ± 0.6 pmol/mg protein/min after the administration of 75 and 100 mg/kg NNLA. The Na+,K+-ATPase activity was measured in the P2 fraction of cortical tissue homogenate. The Na+, K+-ATPase activity was within the normal range (48.3 ± 4.9 μmol/mg protein/h) up to 75 mg/kg of NNLA. At a dose of NNLA of 100 mg/kg, the Na+,K+-ATPase activity decreased to 31.5 ± 0.7 μmol/mg protein/h (p < 0.05). Four animals developed hypoxemia and lactic acidosis. The results demonstrate that inhibition of the cerebral nitric oxide synthase activity in vivo in newborn piglets by intravenous administration of NNLA did not affect the cortical cell membrane Na+,K+-ATPase activity up to a dose of 75 mg/kg. Doses of 100 mg/kg decreased the Na+,K+-ATPase activity, probably by inducing cerebral hypoxia-ischemia.
Transmission of Mother’s Microflora to the Newborn at Birth
Authors: Mändar Reet , Mikelsaar Marika
Published: October 2009

Our aim was to study the initial microbial colonization of the newborns by comparing it with their mothers’ vaginal microflora. Nineteen mother-newborn pairs were examined at delivery. We found a close association, both qualitative and quantitative, between the individually different microflora of a mother’s vagina and that of her newborn. The degree of contamination of the newborn significantly correlated with the counts of microorganisms found in the vagina of mothers. In 85% of investigated individual mother-newborn pairs we revealed similar predominant microorganisms. There were no cases of the mothers and their newborns harbouring similar potentially pathogenic prevailing microorganisms.
Effect of Diabetes on Protein Synthesis Rate and Eukaryotic Initiation Factor Activities in the Liver of Virgin and Pregnant Rats
Authors: García A.M. , Martín M.E. , Blanco L. , Martín-Hidalgo A. , Fando J.L. , Herrera E. , Salinas M.
Published: October 2009

To study the effect of prolonged diabetes on protein synthesis and on the activities of initiation factors eIF-2 and eIF-2B in the liver, female rats were treated with streptozotocin. Some animals were mated and studied on day 20 of pregnancy, whereas others were kept virgin and studied in parallel. The protein synthesis rate was measured with an ‘in vitro’ cell-free system, and was lower in diabetic pregnant and virgin animals than in pregnant and virgin controls (30–60%). The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they always showed a higher protein synthesis rate than their mothers or virgin rats. Protein synthesis rate, RNA concentration, and initiation factor 2 activity were higher in pregnant than in virgin rats. Both activity and level of eIF-2 factor changed in parallel to the protein synthesis rate, although no differences could be detected between control and diabetic animals. The eIF-2B activity in tissue extracts from diabetic virgin rats and fetuses was lower than in extracts from their controls, whereas no differences could be detected between pregnant and virgin control rats nor between pregnant control and pregnant diabetic animals. The percentage of the phosphorylated form of eIF-2 factor, eIF-2(αP), was slightly lower in virgin than in pregnant rats but was unaffected by the diabetic condition, while in diabetic fetuses this parameter was lower than in their corresponding controls. The cyclic adenosine monophosphate dependent protein kinase level was lower in diabetic rats than in controls, whereas no changes in the activity of casein kinase II were found. The isoelectric forms of the β subunit of eIF-2 factor, eIF-2β, were different in the diabetic and the control animals, indicating that insulin deficiency modifies the phosphorylation of specific substrates. Since no differences were detected in RNA or eIF-2 content between control and diabetic rats, translation may, at least partly, be inhibited in the liver by an impairment of peptide chain initiation caused by the decreased eIF-2B activity which nevertheless is independent of elF-2α phosphorylation.
Intestinal Secretory Response to Atrial Natriuretic Peptide during Postnatal Development in the Rabbit
Authors: Brockway Pamela D. , Hardin James A. , Gall Grant
Published: October 2009

The postnatal development of atrial natriuretic peptide (ANP) stimulus-secretion coupling was examined in rabbit ileum. A positive correlation between age and ANP-induced secretory responsiveness was observed. The short circuit current (Isc) response in 14-day animals was significantly (p < 0.05) less than that seen in 21-day, 28-day and adult animals. Animals at 21 days of age were less responsive (p < 0.05) than either 28-day or adult animals which did not differ. The Isc response of infant animals (day 14) to the Cl–– secretagogue 3-isobutyl-1-methylxanthine was blunted in the infant, as was the response to electrical field stimulation. The infant animals had higher basal levels of mucosal cGMP, but were still able to respond to ANP with an elevation in cGMP. The ability of the immature ileum to generate the second messenger molecule cGMP in response to ANP, but not to produce an appropriate Isc response to ANP, indicates infant animals possess underdeveloped secretory mechanisms and lack the ability to effectively couple secretory stimuli to a secretory response.
Developmental Transitions in the Myosin Heavy Chain Phenotype of Human Respiratory Muscle
Authors: Lloyd Janet S. , Brozanski Beverly S. , Daood Monica , Watchko Jon F.
Published: October 2009

We studied the expression of myosin heavy chain (MHC) isoforms in the costal diaphragm (DIA) and the genioglossus (GG) muscles from 16 to 42 weeks gestation in the human using Western blotting techniques. Embryonic/neonatal MHC (MHCemb/neo) was the predominant isoform expressed in the DIA and GG at 16–24 weeks gestation. Subsequently, MHCemb/neo expression declined and the expression of MHCslow and MHC2A increased. At term, the DIA MHC phenotype was a composite of MHCemb/neo (15% of the total MHC complement), MHCslow (32%), MHC2A (47%), and MHC2B (6%); whereas, the GG was largely comprised of MHC2A (74%). We conclude that human DIA and GG demonstrate temporally dependent changes in MHC expression during gestation- and muscle-specific MHC phenotypes as they approach term.
Differential Role of Endothelium-Derived Nitric Oxide in the Modulation of the Systemic and Pulmonary Circulation in Lambs
Authors: Hibler S. , Toga H. , Raj Usha
Published: October 2009

We have studied the differential role of endothelium-derived nitric oxide (EDNO) in the regulation of the systemic and pulmonary circulations of the lamb. Hemodynamic effects of NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg i.v.), an inhibitor of NO synthesis, were determined in juvenile (6 ± 1 weeks old) lambs, under conditions of basal and elevated vasomotor tone. Under basal conditions, L-NAME raised both systemic (SVR) and pulmonary vascular resistances (PVR) by 20-30% (increasing SVR from 0.318 ± 0.013 to 0.385 ± 0.015 mm Hg·min·ml-1·kg and PVR from 0.050 ± 0.003 to 0.067 ± 0.010 mm Hg·min·ml-1·kg). When tone was elevated in the pulmonary circulation with hypoxia (PVR was elevated by 60%, from 0.059 ± 0.010 to 0.094 ± 0.019 mm Hg·min·ml-1·kg), L-NAME treatment resulted in an augmented increase in PVR (PVR increased by greater than 50% to 0.140 ± 0.024 mm Hg·min·ml-1 kg). However, when tone was elevated to a comparable degree in the systemic circulation with angiotensin infusion (SVR was elevated by 60%, from 0.432 ± 0.065 to 0.634 ± 0.113 mm Hg·min·ml-1·kg), the response to L-NAME was not augmented. Our data suggest that the role of EDNO in the modulation of the pulmonary circulation is dependent on the level of vasomotor tone, whereas its role in the systemic circulation is small and is independent of the level of vasomotor tone.
Effects of the Cyclooxygenase Inhibitor Ibuprofen on Retinal and Choroidal Blood Flow during Hyperoxia in Newborn Piglets
Authors: Stiris Tom A. , Suguihara Cleide , Flynn John , Quero Jose , Bancalari Eduardo
Published: October 2009

Purpose: The effect of the cyclooxygenase inhibitor ibuprofen (IB) on choroidal (ChBF) and retinal (RBF) blood flow during hyperoxia was examined in 21 spontaneously breathing newborn piglets. Methods: ChBF and RBF were measured using radiolabelled microspheres before and 30 min after either saline or IB (30 mg/kg, IV) infusion in room air and subsequently, after 90 min of hyperoxia (O2). Results: The basal RBF and ChBF did not change after IB infusion. However, during hyperoxia a significant decrease in RBF was observed in the IB group (54 ± 5 to 37 ± 3 ml/min/100gp < 0.02) and in the control group (54 ± 3 to 37 ± 5 ml/min/100g, p < 0.02). Also, ChBF decreased in the IB group (2,635 ± 446 to 1,670 ± 199 ml/min/100 g, p < 0.02) and in the control group, (2,997 ± 346 to 2,014 ± 246 ml/min/100 g, p < 0.02) during hyperoxia. Conclusions: Despite cyclooxygenase inhibition with IB, RBF and ChBF decreased to the same extent as in the control group following exposure to O2 These data suggest that hyperoxia decrease RBF and ChBF through mechanisms and/or mediators other than the cyclooxygenase by-products of arachidonic acid metabolism.
Deficient Quantitative Expression of CD45 Isoforms on CD4+ and CD8+ T Cell Subpopulations and Subsets of CD45RAlowCD45ROlow T Cells in Newborn Blood
Authors: Chheda Sadhana , Palkowetz Kimberly H. , Rassin David K. , Goldman Armond S.
Published: October 2009

Deficiencies in the quantitative expression of CD45RA and CD45RO on CD4+ and CD8+ T cells and in a population of CD45RAlowCD45ROlow T cells in blood from term newborn infants were found by flow cytometry. The relative frequencies of CD45RO on CD4+ T cells from adults and newborn infants were 72 and 58%, respectively. However, in newborn infants greater than 70% of T cells expressing CD45RO also expressed CD45RA. In addition, the quantitative expression of CD45RA and CD45RO on newborn T cells was significantly less than that found on adult blood T cells.
Perinatal Vitamin A (Retinol) Status of Northern Canadian Mothers and Their Infants
Authors: Godel John C. , Basu Tapan K. , Pabst Henry F. , Hodges Robert S. , Hodges Phyllis E. , Ng Margaret L.
Published: October 2009

Vitamin A (retinol) status was determined in two groups living in the northern part of Canada: native (Indian and Inuit) and non-native (Caucasian). The dietary intake of vitamin A and its plasma concentration were measured prenatally, at delivery and postnatally in mothers. Plasma concentrations were also measured at birth and postnatally in their infants. The mean vitamin A intake of native mothers was significantly lower than that of non-native mothers, 661 ± 485 versus 1,377 ± 1,418 retinol equivalents (p < 0.00005), with a higher risk of deficiency without supplementation, 35% versus 8%. Plasma retinol concentrations, although not in the deficient range, were significantly lower in native than non-native mothers prenatally and postnatally. Infant mean plasma retinol concentrations at birth averaged only 52% of those of their mothers and were significantly lower among native than non-native infants although no clinical evidence of vitamin A deficiency was noted. We speculate that vitamin A supplementation in native Northern Canadian mothers during pregnancy and in their neonates during infancy may have a role to play in the prevention of vitamin A deficiency. We also postulate that plasma retinol concentrations of 50-60% of maternal levels and between 0.7 and 2.5 µmol/l represent a ‘normal’ range for newborn infants.
In vitro Analysis of the Na+-K+ ATPase Activity in Neonatal and Adult Red Blood Cells
Authors: Angelopoulous Margarite , Leitz Helen , Lambert George , MacGilvray Scott
Published: October 2009

We studied the role of albuterol in inducing potassium flux mediated by Na+-K+ ATPase in neonatal cells under hyperkalemic conditions. Using rubidium as a tracer element, we determined net transmembrane potassium flux in neonatal and adult red blood cells (RBCs) maintained in a buffer solution containing 10mM KC1. We demonstrated that under these hyperkalemic conditions, albuterol does not increase the net transmembrane potassium flux of the adult RBC. However, neonatal RBCs maintained in these same hyperkalemic conditions demonstrate a significant 50% increase in net transmembrane potassium flux when exposed to albuterol. We conclude that albuterol may be useful in lowering the serum potassium levels in neonates even with extreme hyperkalemia.
Expression of Complement Regulatory Proteins on Fetal Blood Cells in utero
Authors: Jarvis James N. , Moore Heide T. , Fine Nancy , Berry Stanley M.
Published: October 2009

Since the fetus is semiallogenic to the mother, mechanisms have evolved to protect fetal tissue from the maternal immune response. Among these mechanisms is the expression of cell-surface complement regulatory proteins at the maternal-fetal interface. However, beginning in the third trimester, fetal blood cells are exposed to actively-transported IgG antibody. Thus, we speculated that fetal blood cells would require expression of one or more complement regulators by the early third trimester. Using flow cytometry and Western blots, we have demonstrated the presence of three important complement regulatory proteins in the circulating blood cells of human fetuses. These findings are consistent with the putative biological role of the cell-surface complement regulatory proteins.
Extremely Low Birth Weight Infants Have Lower FcγRIII (CD 16) Plasma Levels and Their PMN Produce Less FcγRIII Compared to Adults
Authors: Payne Nathaniel R. , Fleit Howard B.
Published: October 2009

The purpose of this study was to determine whether decreased FcγRIII expression on the PMN of extremely low birth weight infants (ELBW) is due to decreased receptor synthesis or increased receptor shedding from the PMN surface. 42 ELBW, 12 larger infants and 14 adults were enrolled. Plasma and total cellular FcγRIII were measured by ELISA, and PMN FcγRIII expression was measured by flow cytometry. ELBW PMN plasma membrane expression of FcγRIII as measured by log mean channel fluorescence (5.00 ± 1.98 vs. 10.68 ± 1.61, p < 0.050) and plasma FcγRIII levels were both lower (7.5 ± 6.1 vs. 82.4 ± 64.8 nM, p < 0.05) than in adult controls. In follow-up studies, 14 ELBW (age = 29 ± 14 days, range = 14-56 days) increased PMN expression of FcγRIII (p < 0.001) but not plasma FcγRIII. ELBW had lower total PMN-associated FcγRIII than adults (2.3 ± 0.9 vs. 6.8 ± 2.2 ng/l06 PMN, p = 0.006). ELBW’s PMN produce less FcγRIII than adults’ PMN, and expression of this receptor is developmentally regulated.
Doppler Assessment of Physiological Stenosis at the Bifurcation of the Main Pulmonary Artery: A Cause of Functional Murmur in Neonates
Authors: So Bai-Horng , Watanabe Toyoko , Shimizu Mitsumasa , Yanagisawa Masayoshi
Published: October 2009

A systolic heart murmur is not infrequently recognized in healthy newborn infants, especially those with a low birth weight. This study aimed at assessing the hemodynamics at the bifurcation of the main pulmonary artery using Doppler echocardiography and to correlate the results with this murmur. The peak velocities of main pulmonary artery (MPAV) and right pulmonary artery (RPAV) were studied in 25 low-birth-weight infants who had recovered from acute stage and presented with a systolic murmur, and the ratio of RPAV/MPAV was calculated. Another compatible 25 healthy low-birth-weight infants without a murmur were enrolled as the control group. The initial MPAV values were 79.8 ± 20.7 (range 51–152) cm/s and 80.7 ± 14.2 (range 60–111) cm/s in the heart murmur group and in the control group, respectively (p > 0.05). The initial RPAV values were 193.4 ± 60.2 (range 118–388) cm/s and 99.8 ± 15.5 (range 76–132) cm/s in the heart murmur group and in the control group, respectively (p < 0.0001). The initial RPAV/MPAV ratios were 2.46 ± 0.61 (1.59–3.92) and 1.25 ± 0.14 (0.94–1.47) in the heart murmur group and in the control group, respectively (p < 0.0001). When the murmur disappeared after a period of 2–5 months, no significant differences in the last RPAV and RPAV/MPAV ratios between both groups could be found. The RPAV in the heart murmur group faded significantly to 118.7 ± 16.9 cm/s, and so did the RPAV/MPAV ratio to 1.24 ± 0.12 (p < 0.0001). A transient functional murmur recognized in healthy premature infants at about 1 month of age is caused by the pressure gradient that implies a physiological stenosis at the bifurcation of the main pulmonary artery. The RPAV is higher than the MPAV, and the RPAV/MPAV ratio is usually over 1.5. The RPAV became slower, and the RPAV/MPAV ratio fell as the murmur faded with age.
Staphylococcus epidermidis Sepsis in the Intensive Care Nursery: A Characterization of Risk Associations in Infants <1,000 g
Authors: Johnson-Robbins Lauren A. , El-Mohandes Ayman E. , Simmens Samuel J. , Keiser John F.
Published: October 2009

We undertook to determine Staphylococcus epidermidis colonization patterns and risks of sepsis in a cohort of 82 consecutive intensive care nursery admissions (birth weight 1,285 ± 57 g), with 24 infants weighing < 1,000 g at birth. Colonization was determined by skin and stool cultures collected at three time points. Multiple neonatal variables were classified into three intervals preceding the time of sample collection including the occurrence of S.epidermidis sepsis. 16 infants (20%) developed S.epidermidis sepsis. 81% of these episodes occurred in infants < 1,000 g. Skin colonization was nearly universal at all sampling points. Rectal colonization was 63.6% initially (10 ± 0.4 days), then declined to 32% by the third sample (37 ± 0.4 days). Neither prevalence of skin nor rectal colonization influenced the incidence of sepsis significantly. Statistically significant risk associations for sepsis for the entire intensive care nursery population included: low birth weight, gestational age, presence of a central line, and delayed feeding. For infants < 1,000 g the occurrence of sepsis during the second study time period (54% of the episodes) was associated with preceding steroid exposure. During the third study time period, birth weight and delayed attainment of full enteral feeds showed a statistically significant association with sepsis. We conclude that infants < 1,000 g are at an increased risk of S.epidermidis sepsis. Extreme immaturity, steroid therapy, and prolonged hyperalimentation are all significant risk associations.
Glutathione Status in Diabetes-Induced Embryopathies
Authors: Menegola Elena , Broccia Maria Luisa , Prati Mariangela , Ricolfi Rossana , Giavini Erminio
Published: October 2009

The mechanism involved in diabetes-induced embryotoxicity is still unclear. Mitochondrial alterations probably produced by oxidative stress have been described in embryos developing in a diabetic environment. Furthermore, oxygen radicals-scavenging enzymes can reduce the embryotoxic effects induced by diabetic conditions. In this work we tried to test if glutathione (GSH), a tripeptide implicated in cellular protection against reactive oxygen species, is involved in diabetes-related embryotoxicity. Rat embryos were explanted on day 11 on gestation from normal and from streptozotocin-diabetic mothers. The embryos were examined morphologically, then protein, DNA and GSH were determined both in embryos and in their visceral yolk sacs. The embryos explanted from diabetic mothers showed signs of developmental retardation and 16% were morphologically abnormal. GSH content was reduced in these embryos in comparison to control, but the GSH/protein in the visceral yolk sacs of conceptuses explanted from diabetic mothers was higher than in control visceral yolk sacs. Our hypothesis is that the reduction of embryonic GSH is a consequence of the alteration in GSH transport across the yolk sac endodermal cells damaged by diabetic conditions. The observed reduction in embryonic GSH could reduce the protection against the oxidative stress condition described in diabetic pathology.
Differential Expression of fos and jun Family Members during Murine Postnatal Intestinal Development
Authors: Blais Sylvie , Boudreau François , Thorneloe Kevin , Asselin Claude
Published: October 2009

We have examined the patterns of expression of members of the fos and jun families of transcription factors during murine postnatal intestinal development. Northern analysis showed increases in fosB, c-fos, and junB mRNA levels in both proximal jejunum and colon. These increases coincide with weaning, a period of major changes in intestinal cell proliferation and migration. Administration of dexamethasone to suckling mice resulted in transient induction of c-fos mRNA levels in all gut segments. Thus, modifications in expression of certain members of the fos and jun families in vivo correlate with major maturational changes during murine intestinal development and support a role for these transcription factors in the regulation of intestinal functions.
Influence of Sleep State and Respiratory Pattern on Cyclical Fluctuations of Cerebral Blood Flow Velocity in Healthy Preterm Infants
Authors: Rehan Virender K. , Fajardo Carlos A. , Haider Zia , Alvaro Ruben E. , Gates Donald B. , Kwiatkowski Kim , Nowaczyk Bogdan , Rigatto Henrique
Published: October 2009

To examine the influence of sleep state, respiratory pattern, and ventilation on cyclical fluctuations (CF) in cerebral blood flow (CBF) velocity (CBFV), we studied 21 ‘healthy’ preterm infants: birth weight 1,790 ± 162 g (SEM), study weight 1,960 ± 165 g, gestational age 32 ± 1 weeks, postnatal age 20 ± 4 (range 8–57) days. The CBFV was measured using on-line pulsed Doppler ultrasound by insonating the middle cerebral artery. Breathing was measured using a flow through system. The sleep state was monitored according to conventional criteria. Three hundred and seventy-five epochs of 1 min each were analyzed; 207 during quiet sleep (QS) and 168 during rapid eye movement (REM) sleep. CFs in CBFV were detected in all babies. The frequency of CF ranged from 0.5 to 6 cycles/min. The proportion of epochs showing CF was similar during both sleep states (56% QS vs. 59% REM; p = NS). Although the mean CBFV (cm/s) was similar in these two sleep states, the mean coefficient of variation, a measure of CF amplitude, was significantly higher during REM as compared with QS (6 ± 0.5 vs. 4.3 ± 0.2%; p < 0.05). Similarly, the mean CBFVs were similar with various respiratory patterns, but the coefficient of variation was significantly higher in periodic and apneic patterns as compared with regular and irregular respiratory patterns (5.6 ± 0.6% periodic, 5.6 ± 0.3% apneic, 3.6 ± 0.3% regular, and 4.1 ± 0.5% irregular; p < 0.05). The amplitude of CF was associated with the variability of the heart rate (p < 0.05), but not with the variability of the respiratory measurements. These findings suggest: (1) REM sleep is associated with a greater CBF variability than QS, and (2) periodic and apneic breathing are associated with a greater CBF variability than regular or irregular breathing. We speculate that sleep state and respiratory pattern do not determine but modulate the CBF. Our data suggest that in studies involving interpretation of CBFV data using the Doppler technique, breathing patterns should be taken into account in addition to sleep state.
Cord Blood Neutrophil Responses to Polyunsaturated Fatty Acids: Effects on Degranulation and Oxidative Respiratory Burst
Authors: Ferrante Antonio , Carman Kathie , Nandoskar Madhuri , McPhee Andrew , Poulos Alfred
Published: October 2009

Lipid mediators such as arachidonic acid (AA) generated during inflammation play an important role in stimulating phagocytic cell responses. Since cord blood neutrophils show reduced responses to agonists such as the bacterial tripeptide f-Met-Leu-Phe (fMLP), it would be of interest to know whether cord blood neutrophils show normal or reduced responses to AA and other fatty acids. The data showed that the polyunsaturated n-6 fatty acid (PUFA) AA stimulated cord blood neutrophils to produce a respiratory response (measured by chemiluminescence) and degranulation. Other PUFAs, eicosapentanoic acid and docosahexaenoic acid, elicited similar responses in cord blood neutrophils. Specific granule release and chemiluminescence response in cord blood neutrophils were evident at 0.1–0.5 μg/ml of PUFA, concentrations normally found in vivo during inflammation or following diets enriched with n-3 fatty acids. Neutrophil responses to PUFA were significantly better than those to either fMLP or phorbol myristate acetate. Cord blood neutrophils primed with PUFA showed enhanced responses to fMLP. These results suggest that cord blood neutrophils respond to a similar degree to adult neutrophils to the AA which is generated during the inflammatory response and to the n-3 fatty acids eicosapentaenoic acid/docosahexaenoic acid, both of which may be used in diet manipulation of neurological function and immunological reactions.
Human Colostrum Stimulates Cytokine Production
Authors: Bessler H. , Straussberg R. , Hart J. , Notti I. , Sirota L.
Published: October 2009

The effect of human colostrum on the production of IL-1, IL-3 and IL-6 by peripheral blood mononuclear cells (PBMCs) has been investigated. The aqueous phase of human colostrum significantly stimulated the production of these three cytokines. These findings show the importance of breast feeding not only as a well-balanced nutrient supply but also as a source for growth-promoting factors. It is suggested that the enhanced secretion of IL-1, IL-3 and IL-6 induced by human colostrum may compensate for the lower capacity of neonatal PBMCs to produce these cytokines. It is also possible that, by stimulating the secretion of these cytokines, breast feeding may provide an additional mechanism for the regulation of the neonatal immune system and hematopoiesis.
Nitric Oxide Modulates Glomerular Filtration and Renal Blood Flow of the Newborn Rabbit
Authors: Ballèvre Laurence , Thonney Michèle , Guignard Jean-Pierre
Published: October 2009

The current study was performed in 17 anesthetized and mechanically ventilated newborn rabbits to investigate the role of nitric oxide (NO) in the regulation of basal renal function of the immature kidney. Renal blood flow and glomerular filtration rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. In 9 newborn rabbits (group 1), L-NAME, a NO synthesis inhibitor, significantly increased the renal vascular resistance by 31 ± 9% and decreased the renal blood flow by 20 ± 6%. The fraction of filtration significantly increased by 8 ± 5% despite a delayed decline in glomerular filtration rate by 13 ± 5%. Mean arterial pressure and heart rate were not altered. In 8 additional newborn rabbits (group 2), L-arginine, the physiological precursor of NO synthesis, partially reversed the renal hemodynamic changes induced by L-NAME. The present results demonstrate that the decrease in NO production induced by L-NAME (1) significantly affects the renal microcirculation of the immature newborn rabbit kidney and (2) predominantly increases the postglomerular renal vascular resistance. Endogenous NO thus appears to play a major role in maintaining the basal perfusion of the immature kidney.
Nitric Oxide and the Immature Kidney
Authors: Ballèvre L. , Solhaugh M.J. , Guignard J.-P.
Published: October 2009

Nitric oxide (NO) is a very potent vasodilator synthesized from L-arginine by endothelial cells. By activating guanylate cyclase, it promotes vasodilatation of adjacent smooth muscle cells. NO is thus involved in the control of vascular tone in various organs. There is increasing evidence that NO is tonically synthesized within the kidney and plays a crucial role in the modulation of renal hemodynamics and excretory function. The blockade of basal NO synthesis has been shown to result in decreases in renal blood flow and, to a lesser extent, in glomerular filtration rate. NO may also be involved in sodium excretion. In the neonatal period, a time associated with a hyperactivation of vasoactive systems, NO seems to play a greater role than in the adult. It could also be implicated in the response to vasoconstrictive stresses, such as perinatal hypoxia, frequently encountered during this period.
Incidence of Ischemic-Hemorrhagic Cerebral Lesions in Premature Infants of Gestational Age ≤ 28 Weeks: A Prospective Ultrasound Study
Authors: Claris O. , Besnier S. , Lapillonne A. , Picaud J.C. , Salle B.L.
Published: October 2009

While it is well accepted that the incidence of intraventricular hemorrhage (IVH) increases with decreasing gestational age (GA), the majority of studies report their findings on the basis of birthweight (BW) rather than GA. Over a 5-year period, 199 infants born at or below 28 weeks of gestation were entered into a prospective cranial ultrasound study stratified according to GA. One hundred and five (53%) had normal ultrasound findings. The overall incidence of IVH, as expected, rose with decreasing GA but we were unable to show any clear influence of BW or growth retardation on its occurrence. Incidence of grades I, Ha, lib and III IVH were 8, 10, 16 and 11%, respectively. Leukomalacia, bleeding in the posterior fossa and in the cerebellum occurred in 4, 7 and 2% of the population, respectively.
Effect of Dopamine Antagonism on the Behavioral and Hemodynamic Responses to Cocaine in Piglets
Authors: Monitto Constance L. , Feuer Pamela , O’Rourke Maureen , Shaw Leslie , Kurth Dean
Published: October 2009

Cocaine (1.5 mg/kg i.v.) was administered to awake newborn piglets that were pretreated with either intravenous saline (placebo) or SCH23390, a dopamine antagonist, to study dopamine’s role in cocaine’s vascular and behavioral actions. In the placebo group, cocaine increased the locomotor activity and cerebellar and cardiac blood flow (31 ± 36 and 72 ± 66%), but decreased choroid plexus and renal blood flow (47 ± 23 and 18 ± 19%). In the SCH23390-treated group, cocaine did not affect organ blood flow or locomotor activity. Cocaine transiently increased the mean arterial blood pressure in both groups (10 ± 7 and 18 ± 13%). These data indicate that the behavioral and blood flow responses to cocaine in cerebellum, choroid plexus, heart, and kidneys are mediated by dopamine, whereas the arterial pressor response to cocaine is not.
Stability of Gastrin in the Gastrointestinal Lumen of Suckling, Weanling and Adult Pigs
Authors: Xu Ruo-Jun , Mao Y.-L. , Tso Man-Yin W.
Published: October 2009

It has been reported in the literature that a large quantity of gastrin is released into the gastric lumen in various species. This study was aimed to examine the stability of gastrin in the gastrointestinal (GI) lumen of pigs. Iodine-labelled little (G17) and big gastrin (G34) were incubated in vitro with the GI luminal fluids of suckling, weanling and adult pigs at 37°C for 20 min, and the degradation of the peptide was measured by monitoring the generation of trichloroacetic acid soluble radioactivity. The degradation rate of G17 in the gastric fluids of all animals was less than 10%, while the degradation of G34 was less than 15% in the gastric fluids of suckling and adult pigs and about 25% in the gastric fluids of weanling pigs. The degradation rates of G17 and G34 in the small intestinal fluids of suckling pigs were between 18 and 30%, and were significantly lower than the corresponding rates in the intestinal fluids of weanling and adult pigs, the latter were between 35 and 67%. Addition of defatted porcine colostrum or its components, the casein or acid-soluble fraction, inhibited gastrin degradation in the intestinal fluids with the casein fraction having highest inhibition potency. These results indicate that gastrin is stable in the GI lumen of the suckling pigs and porcine colostrum protects gastrin from luminal hydrolysis in the small intestine, suggesting a potential physiological role of luminally released gastrin in suckling animals.
Intravenous Immune Globulin in Neonatal ABO Isoimmunization: Factors Associated with Clinical Efficacy
Authors: Hammerman Cathy , Kaplan Michael , Vreman Hendrik J. , Stevenson David K.
Published: October 2009

Objective: Intravenous immune globulin (IVIG) reduces jaundice in many but not all cases of neonatal isoimmunization. We sought to elucidate the type of infant most likely to benefit from IVIG administration by attempting to define pretreatment parameters associated with both clinical symptomatology and therapeutic responsiveness to IVIG. Methods: Term, healthy Coombs-positive infants were studied prospectively. IVIG was administered if, despite phototherapy, serum bilirubin reached ≥ 222 μmol/l (13 mg/dl) at ≤ 24 h of age and/or ≥ 274 μmol/l (16 mg/dl) at > 24 h of age. Clinical data including serial serum total bilirubin levels, rate of bilirubin rise on day 1 of life, serial corrected carboxyhemoglobin levels (a sensitive indicator of hemolysis) and total hemoglobin (tHb) levels were collected. Results: Infants were classified as IVIG responders (n = 18), those in whom total serum bilirubin levels either remained stable or decreased following IVIG administration; IVIG nonresponders (n = 5), those who developed a total serum bilirubin of ≥ 2 mg/dl greater than pre-IVIG bilirubin levels within the first 24 h after IVIG administration, or nontreated, those not meeting IVIG treatment criteria (n = 13). Four of the five nonresponders proceeded to require exchange transfusion vs. none of the others (p < 0.001). Four of the five nonresponders had a pretreatment rate of bilirubin rise of > 1 mg/dl/h as compared with only 1 of 18 responders and none of the nontreated (p < 0.001). Pretreatment tHb levels were also different (13.2 ± 1.3 vs. 15.5 ± 2.3 vs. 17.7 ± 2.4 g/dl for nonresponders vs. responders vs. nontreated infants, respectively; p < 0.005). The highest pretreatment COHbc levels were seen in the nonresponders (1.8 ± 0.7 vs. 1.4 ± 0.3 vs. 0.9 ± 0.3% tHb, respectively). Conclusions: Our 3 groups represent a spectrum of hemolysis, ranging from severe to moderate to mild. This spectrum appears to relate not only to the severity of hemolysis, but also to the therapeutic responsiveness to IVIG. We speculate that some or all of the factors identified can be used prospectively to predict the subsequent clinical course of ABO-incompatible infants and to facilitate optimal management.
Fetal Mouse Lung Ultrastructural Maturation Is Accelerated by Maternal Thyrotropin-Releasing Hormone Treatment
Authors: Devaskar Uday P. , Govindrajan R. , Heyman Sarah , Sosenko Ilene R.S. , deMello Daphne E.
Published: October 2009

Maternal administration of thyrotropin-releasing hormone, alone or in combination with corticosteroid, accelerates functional, morphologic and biochemical fetal lung maturation. However, the dose-response relationship of maternal thyrotropin-releasing hormone treatment and acceleration of fetal lung ultrastructural maturation or disaturated phosphatidylcholine content has not been investigated. We administered (i.p.) saline or thyrotropin-releasing hormone (0.2, 0.4 or 0.6 mg/kg/dose) to the pregnant Balb/c mouse on days 16 and 17 (b.i.d.) and on day 18 of gestation (1 h prior to killing). Morphometric ultrastructural analysis and quantitation of disaturated phosphatidylcholine content was done on the 18-day gestation fetal lung. Maternal thyrotropin-releasing hormone treatment resulted in an increase in the number of lamellar bodies and depletion of glycogen in fetal lung type II cells, and an increase in the lung airspace to parenchymal ratio. In addition, a striking difference in the pattern of lung growth was noted in the thyrotropin-releasing-hormone-treated (0.4 and 0.6 mg/kg/dose) groups. These lungs had larger air spaces, thinner alveolar septae and more air-blood barriers. Maternal thyrotropin-releasing hormone treatment did not influence fetal lung disaturated phosphatidylcholine content. We conclude that in the mouse, maternal thyrotropin-releasing hormone treatment enhances fetal lung structural maturation and propose that thyrotropin-releasing hormone plays a role in mammalian fetal lung growth.
Possible Mechanism for Late Gestational Development of the Antioxidant Enzymes in the Fetal Rat Lung
Authors: Frank Lee , Price Lalitha T. , Whitney Philip L.
Published: October 2009

We hypothesized that a possible mechanism to explain the significant increases that occur in the pulmonary antioxidant enzyme (AOE) system late in gestation might be an endogenous increase in the normal reactive O2 substrates for these enzymes. We found that lung O2 free radical formation increased -175% between fetal day 18 and birth (p < 0.01). We also found that late fetal rat lung mitochondrial and microsomal rates of AOE substrate (H2O2) generation increased markedly, and there was also significantly increased lung lipid peroxidation products with increasing gestational age. These definite elevations in reactive O2 species production in parallel with the time course of maturational elevations in the pulmonary AOE system, suggest that increasing enzyme substrate concentrations could be a primary controlling mechanism for increasing lung AOE gene expression in preparation for birth of the newborn.
Pharmacokinetics of Erythropoietin following Single-Dose Subcutaneous Administration in Preterm Infants
Authors: Krishnan Ravi , Shankaran Seetha , Krishnan Murali , Kauffman Ralph E. , Kumar Praveen , Lucena José;
Published: October 2009

The pharmacokinetics of recombinant human erythropoietin was studied in 12 very low birth weight preterm infants < 32 weeks of gestation after subcutaneous administration of 300 IU/kg at a postconceptional age of 34 (32-37) weeks and a weight of 1,505 (1330–1,740)g (median and range). The administration of recombinant human erythropoietin produced a rapid increase n serum erythropoietin levels with a peak level of 362.8 mlU/ml at 8.9 h. The area under the curve was 8,177.5 (4,597.1–15,453.0) mlU/ml/h, the absorption half-life was 5.5 (1.6–6.6) h, the elimination half-life was 7.9 (5.6–19.4) h, and the residence time was 19.6 (5.1–32.6) h (all values reflect median and range). There was no significant correlation between absorption and elimination half-life of erythropoietin and birth weight, gestational age, sex, and age and weight of the infants at the time of administration of erythropoietin. Based on absorption and elimination kinetics, the dosing interval for subcutaneous administration must not be < 48h.
Vibroacoustic Stimulation with a Complex Signal: Effect on Behavioral State in Fetal Sheep
Authors: Abrams Robert M. , Schwab Matthias , Gerhardt Kenneth J. , Bauer Reinhard , Peters Aemil J.M.
Published: October 2009

An ideal vibroacoustic stimulus for testing fetal reactivity has yet to be developed. In the present study in fetal sheep we tested the effect on behavioral state of an amplitude and frequency-modulated signal produced at the abdominal surface of the ewe. The stimulus was presented during periods of fetal non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Evaluation of behavioral state was accomplished by visual observation of strip-chart recordings. Assessed in this manner, vibroacoustic stimulation during NREM sleep consistently resulted in a change to an indeterminate state. However, stimulation during REM sleep failed to have an effect. Additional evaluation applying spectral analysis to the fetal electrocorticogram during stimulation in NREM sleep revealed a marked decrease in delta band power from 100 to 27 ± 5% and in theta band power from 100 to 40 ± 4% resulting in a decrease in total power from 100 to 35 ± 4% (p < 0.05). Stimulation during REM sleep revealed a significant increase in beta band power from 100 to 123 ± 14%. Vibroacoustic stimulation in both NREM and REM sleep led to an increase in spectral edge frequency, implying central arousal.
Effects of Preweaning Environmental Stimulation on Neuronal and Behavioral Impairment Produced by Undernutrition
Authors: Pascual Rodrigo , Hervias María C. , Figueroa Hé;ctor R.
Published: October 2009

The present study investigates the effects of sensorimotor stimulation on the basal dendrogenesis of superficial cerebrocortical neurons and the accomplishment in the associated exploratory behavior in rats simultaneously exposed to nutritional deprivation. Sprague-Dawley albino rats were submitted to nutritional-environmental influences from birth to the 21 st postnatal day. Exploratory behavior was assessed by the evaluation of locomotor activity in the open-field apparatus. In order to evaluate changes in neuronal morphology induced by nutritional-environmental variables, brains were stained according to the Golgi-Cox-Sholl procedure. Dendritic development was assessed under camera lucida by measuring basal dendritic branching of layer II and III pyramidal neurons, located in the dorsomedial region of the visual cortex of the rat. Morphometrical analysis revealed that both basal dendritic length and branching were significantly reduced by undernutrition. In contrast, environmental stimulation during the suckling period compensated for the neuronal impairment produced by protein-calorie deprivation. An improvement was also observed in exploratory behavior although to a lesser degree, as shown by the open field test data. In conclusion, the present results indicate that sensorimotor stimulation applied during the period of fastest rate of cortical cytodifferentiation compensates for neuronal and behavioral impairment produced by undernutrition.
Fetal Gammaglutamyl Transferase Activity: Clinical Implication in Fetal Medicine
Authors: Mirlesse Véronique , Jacquemard François , Daffos Fernand , Forestier François
Published: October 2009

In a retrospective study of 3,129 fetal blood samples, we first determined normal values for gammaglutamyl transferase (GGT) activity and found 33 cases with a mean GGT level of 961.8 U/l (prevalence 1.05%) corresponding to more than 10-fold normal values. In such extreme cases, elevations of GGT activity in fetal blood have been poorly studied. The goal of this work was to correlate this highly abnormal biological finding with pathological fetal conditions and try to better understand the pathophysiological mechanisms. The most frequent underlying disorders were infections (n = 11), renal or bowel malformations (n = 12) and genetic abnormalities (n = 5). Two cases of cystic fibrosis and one case of fetal alcohol syndrome were also encountered. In another 2 cases, no explanation was found.
Changes in Myocardial A1 Adenosine Receptor and Message Levels during Fetal Development and Postnatal Maturation
Authors: Matherne Paul , Byford Anne M. , Gilrain Joan T. , Dalkin Alan C.
Published: October 2009

Previously we have shown myocardial adenosine A1 receptors are up-regulated during the newborn period. The timing of the increase or the mechanism of the changes are not known. The purpose of the present study was to (1) determine the time course of increased A1 adenosine receptors during fetal development and (2) determine if A1 adenosine receptor regulation is secondary to changes in A1 receptor mRNA levels. A1 adenosine receptor density was determined in whole hearts from fetal rats at 14 and 19 days’ gestation and from newborn and adult rats using standard receptor-binding techniques. A quantitative PCR assay was developed to measure A1 adenosine receptor mRNA using total RNA samples from the above ages. A1 receptor density (fmol receptor/mg protein) increased during late gestation (79 ± 14 and 122 ± 7 in 14 and 19 days’ gestation respectively) peaked during the newborn period (136 ± 12) and decreased in the adult rat (36 ± 5). A1 receptor message levels (fg message/μg total RNA) changed in parallel to receptor density (7.2 ± 1.7, 15.6 ± 1.8, 19.9 ± 4.3 and 9.9 ± 1.3 in 14 and 19 days’ gestation, newborn and adult respectively). These results provide evidence for transcriptional control of A1 receptor density and the increased receptor density in the newborn heart supports a possible role for the A1 receptor in the transition to the extrauterine circulation.
Effect of Chronic Erythropoietin Administration on Plasma Iron in Newborn Lambs
Authors: Peters Charles , Georgieff Michael K. , de Alarcon Pedro A. , Cook Robert T. , Burmeister Leon F. , Lowe Lance S. , Widness John A.
Published: October 2009

Erythropoietin, the primary stimulator of erythropoiesis, represents an important potential therapy for the anemia of prematurity. Enhancement of the therapeutic benefit of recombinant human erythropoietin (rhEp) in very-low-birth-weight infants will require a better understanding of rhEp’s pharmacodynamic effects including its interaction with iron in stimulating erythropoiesis. The purpose of this study was to determine the effects of chronic rhEp administration on plasma iron levels and hematopoiesis using a twin lamb model. Nine pairs of twin lambs in which one twin was randomized to receive rhEp, and the other saline, were studied during a 1-week baseline and a subsequent 4- to 5-week treatment period. The effects of therapy on plasma iron levels and erythropoiesis were measured by integrating the areas under the concentration-time curves (AUC) of the study variables. During the rhEp treatment period, significantly greater negative daily AUCs were observed in the rhEp-treated lambs for plasma iron concentration (p = 0.0008), while significantly greater positive daily AUCs were observed for hemoglobin concentration (p = 0.04) and reticulocyte count (p = 0.02). In the rhEp-treated group, pretreatment iron concentrations were directly associated with the magnitude of the iron response during treatment such that the greater the pretreatment iron, the greater the daily AUC below the plasma iron concentration-time plot (r = ––0.66, p = 0.05). For the placebo-treated group, this association tended toward, but did not achieve, statistical significance (r = ––0.52, p = n.s.). These observations suggest that treatment of rapidly growing newborn lambs with rhEp results in increased iron utilization due to increased erythropoiesis and depends on iron status at the initiation of rhEp treatment. Use of the term neonatal lamb model offers advantages over studies in human infants for more detailed or invasive examinations of the interaction of iron and rhEp treatment.