bluuebunny/crossref_metadata_2025 huggingface dataset:
Maturation of A71915-Dependent Inhibition of Atrial Natriuretic Peptide-Stimulated Cyclic GMP Production in Isolated Rat Glomeruli
Authors: Norling Laura L. , von Geldern Thomas , Chevalier Robert L.
Published: October 2009

Atrial natriuretic peptide (ANP) regulates glomerular hemodynamics by interaction with biologic receptors (GC-A/ANP) that possess particulate guanylyl cyclase activity. In a previous study we have shown a developmental difference in glomerular response to ANP where preweaned glomeruli produced significantly less extracellular cGMP in response to ANP. Because of the possibility that functional differences in the ANP biologic receptor might exist during development, further characterization of GC-A/ANP receptor response in glomeruli of developing rats was done using a structural analogue of ANP. A71915 (Abbott Laboratories) is a structural analogue of ANP which has been shown to inhibit activation of ANP receptor-associated guanylyl cyclase in vascular smooth muscle cells. The purpose of this study was to investigate the ability of A71915 to inhibit ANP-stimulated cGMP response in isolated glomeruli of adult and preweaned rats. Isolated glomeruli from preweaned or adult rat kidneys were preincubated for 15 min with A71915 (10––5M) prior to addition of ANP (up to 10––6M). Glomerular response of production of intracellular and extracellular cGMP was measured by radioimmunoassay. Adult glomeruli produced significantly greater amounts of extracellular cGMP compared to preweaned glomeruli for concentrations of ANP > 10––9M. Infant glomeruli had a significant decrease in the production of ANP-stimulated intracellular cGMP in the presence of A71915 (10––5M), whereas extracellular cGMP production was unchanged. In contrast both ANP-stimulated intracellular and extracellular cGMP were significantly decreased by A71915 in adult glomeruli. These results demonstrate the maturation of the glomerular response to ANP. The lack of effect of A71915 on extracellular release of cGMP by glomeruli from preweaned rats is likely due to immaturity of the cGMP extrusion mechanism rather than a reduced GC-A/ANP receptor response or signal transduction.
Hemodynamic Interaction of Chloralose Pretreatment with Subsequent β-Adrenergic Receptor Antagonism in Lambs
Authors: Covert Robert F. , Drummond Willa H.
Published: October 2009

α-Chloralose is a commonly used anesthetic agent in cardiovascular research despite a paucity of information whether it may have important pharmacologic interaction with subsequently given adrenergic drugs. To assess any potential pharmacologic interaction, we studied the cardiovascular response to β-adrenergic receptor antagonism (propranolol, 1 mg/kg i.v.) after either chloralose (30 mg/kg i.v.) or saline control in paired studies in 10 chronically instrumented neonatal lambs. Chloralose increased heart rate by 46% as compared to control (283 ± 37 vs. 194 ± 48 beats/ min, p = 0.0002) and had no significant effect on cardiac output; chloralose also increased mean pulmonary arterial pressure by 45% (27 ± 13 vs. 19 ± 6 mm Hg, p = 0.050) and pulmonary vascular resistance by 79% (0.211 ± 0.13 vs. 0.118 ± 0.04 mm Hg/ml/kg/min, p = 0.050). The group pretreated with chloralose had significantly elevated heart rate (186 ± 23 vs. 157 ± 31 beats/min, p = 0.03), mean pulmonary arterial pressure (29 ± 9 vs. 22 ± 6 mm Hg, p = 0.03) and pulmonary vascular resistance (0.228 ± 0.13 vs. 0.130 ± 0.05 mm Hg/ml/kg/min, p = 0.05) after propranolol as compared to the conscious saline-treated group. We conclude that pretreatment with chloralose as an anesthetic agent may produce important pharmacologic interaction with subsequent adrenergic drugs in neonatal lambs. While anesthesia may be necessary in animal research, investigators should be aware that the anesthetic agent may also qualitatively and quantitatively influence measured outcome variables.
Assessment of Gut Intraepithelial Lymphocytes during Late Gestation and the Neonatal Period
Authors: Machado C.S.M. , Rodrigues M.A.M. , Maffei H.V.L.
Published: October 2009

Intraepithelial lymphocyte counts (IEL % enterocytes) were carried out in histological samples of jejunal, ileal and appendiceal mucosa of 39 neonates, aged from birth to 28 days. Correlations between IEL counts and developmental factors, namely gestational age, birth weight and intrauterine growth, as well as neonatal infections or feeding state were performed. No significant differences were observed among neonates grouped according to birth weight, intrauterine growth or neonatal infections. The pattern of feeding, however was associated with significantly higher IEL counts (p < 0.02) in the ileum in oral/enterally fed neonates than in the unfed or parenterally fed. Full-term neonates also had higher counts in the ileum (p < 0.02). In this group, oral/enterally fed neonates had the higher values. Thus, besides in utero development, the pattern of feeding might be considered as an important modulating factor on IEL postnatal expansion.
Developmental Electrophysiology of Encainide and Its Major Metabolites on the Purkinje Fiber Action Potential
Authors: Case Christopher L. , Hewett Kenneth W. , Gillette Paul C.
Published: October 2009

Objective. With clinical data suggesting that neonates may be more prone to developing electrophysiologic side effects from encainide, this study investigates the in vitro developmental electrophysiologic effects of encainide and its major metabolites on the action potential parameters of the canine cardiac Purkinje fiber. Methods. With standard microelectrode techniques, the in vitro tonic and rate-related effects of encainide, and its major metabolites (3-methoxy-4-hydroxy encainide, MODE, and O-dimethyl encainide, ODE) were investigated using mature and immature canine cardiac Purkinje fibers. Results. The significant developmental differences in the effects of these compounds on the canine Purkinje fiber illustrated in this study are: (1) 1 × 10––6M encainide depresses Vmax in neonatal Purkinje fibers, yet not in the adult. (2) 1 × 10––6M MODE lengthens APD90 in the neonate, yet it has no substantial effect in the adult. (3) 1 × 10––6M ODE shortens APD90 in the adult, yet it has no appreciable effect on the neonate. (4) Rate-related effects of encainide and ODE are more pronounced in adult Purkinje fibers. Conclusion. In contrast to other in vitro studies on class I anti-arrhythmic agents, neonatal canine Purkinje fibers seem to be more sensitive than the adult to the tonic depolarization depressant effect of encainide. This in vitro sensitivity parallels clinical experience with the drug in neonatal patients. Although encainide is no longer available for clinical use, these findings highlight the fact that the immature conduction system may show markedly different sensitivities to different class I agents despite the fact that these agents share similar qualitative pharmacologic properties.
Prostaglandin E2 in Cerebrospinal Fluid of Fetal and Newborn Sheep: Central versus Peripheral Source
Authors: Jones Sarah A. , Adamson Lee , Bishai Isis , Engelberts Doreen , Norton Jennifer L. , Coceani Flavio
Published: October 2009

During the perinatal period, prostaglandin (PG) E2 levels show parallel changes in cerebrospinal fluid (CSF) and blood which may be important for the adaptation of the fetus to extrauterine life. It is not known, however, whether PGE2 in the CSF originates from a local or a peripheral source. Experiments were carried out in term fetal and newborn sheep chronically instrumented with a cannula inside the third ventricle and vascular lines. Indomethacin was given intracerebroventricularly (i.c.v.) (50 or 100 µg at hourly intervals), alone or in combination with intravenous (i.v.) PGE2 (1 or 1.5 µg/kg/min). In the fetus, i.c.v. indomethacin reduced PGE2 levels in both CSF and plasma. Conversely, no significant change was noted at either site when indomethacin was given i.c.v. to the newborn. At both ages, PGE2 increased in the CSF during i.v. infusion of the compound, but this elevation was proportionately smaller than in plasma. We conclude that, in the perinatal period, brain and peripheral circulation function as separate compartments with respect to PGE2, though there is passage of the compound across the blood-brain barrier. Results provide indirect evidence that perinatal brain produces PGE2 in measurable amounts.
Effects of Calcitriol on Expression of Triiodothyronine-Stimulated Renal Tubular Transport of p-Aminohippurate in Rats of Different Ages
Authors: Bräunlich Helmut , Schmidt Mirko
Published: October 2009

Following treatment of rats of various age groups with calcitriol (2 µg/kg b.w., 3 days, once daily) renal tubular transport of p-aminohippurate (PAH) is reduced in kidney cortical slices prepared from 5-, 15-, 33-, and 55-day-old rats. The decrease in renal excretion of PAH following such treatment has a longer degree and is demonstrable in 15- and 33-day-old rats only. Repeated treatment with calcitriol provokes a decrease in body weight, statistically significant in 5- and 55-day-old rats. In 33- and 55-day-old rats repeated treatment with calcitriol (2 µg/kg b.w., 3 days, once daily) causes an increase of kidney weight. Repeated treatment with calcitriol is connected with an increase in plasma level and in renal excretion of calcium, statistically significant in most age groups. In rats of various age groups, renal tubular transport of PAH can be stimulated by repeated administration of triiodothyronine (T3; 100 µg/kg b.w., 3 days, once daily). This increase in PAH transport, measured in kidney cortical slices, cannot be observed in rats simultaneously treated with calcitriol and T3. Obviously, the expression of higher transport rates for PAH can be prevented by renal effects of calcitriol. Simultaneous treatment with T3 and calcitriol causes an increase in kidney weight and a decrease in body weight in rats of various age groups.
Brain Blood Flow Responses to Indomethacin during Hemorrhagic Hypotension in Newborn Piglets
Authors: Louis P.T. , Yamashita Y. , Del Toro J. , Michael L.H. , Contant C.F. , Goddard-Finegold J.
Published: October 2009

Indomethacin has been shown to reduce cerebral blood flow and cerebral blood flow velocities in newborn infants and animals of various species. To answer the question of whether there may be a compromise of cerebral perfusion in hypotensive infants who have been treated with indomethacin, cerebral blood flow and cerebral vascular resistance were determined in 10 control and 16 indomethacin-treated 1-day-old piglets during (1) steady state conditions; (2) 10 min after the administration of saline or a 0.2-mg/kg dose of indomethacin; (3) 1 h after saline or indomethacin administration, and (4) 10 min after induction of moderate hemorrhagic hypotension. Mean arterial blood pressures increased immediately after the infusion of indomethacin in the experimental group. Cerebral blood flows did not change throughout the study despite hemorrhagic hypotension in controls; cerebral blood flows were significantly decreased 10 min after indomethacin infusion in the experimental animals. However, total and regional cerebral blood flows were not further decreased in the presence of moderate hypotension. Cerebral vascular resistance increased 10 min after indomethacin infusion but returned to steady state 1 h following the indomethacin dose. These results suggest that indomethacin lowers baseline cerebral blood flow, but does not impair cerebrovascular regulatory responses during acute, moderate hemorrhagic hypotension in the newborn piglet.
Effect of Cyclooxygenase Inhibition on Brain Cell Membrane Lipid Peroxidation during Hypoxia in Newborn Piglets
Authors: McGowan Jane E. , McGowan III Joseph C. , Mishra Om P. , Delivoria-Papadopoulos M.
Published: October 2009

To test the hypothesis that indomethacin, an inhibitor of cyclooxygenase, reduces free radical-induced brain cell membrane changes during cerebral hypoxia, we determined levels of brain cell membrane lipid peroxidation products and Na+, K+-ATPase activity as indicators of free radical production and membrane function, respectively, in 29 newborn piglets divided into 4 groups. Eight saline- and 4 indomethacin-treated normoxic animals served as controls; 8 saline-pretreated piglets and 9 piglets pretreated with indomethacin were exposed to hypoxic hypoxia for 60 min. Cerebral hypoxia was documented using 31P-NMR spectroscopy. In saline-pre-treated hypoxic animals Na+, K+-ATPase activity decreased significantly and levels of membrane lipid peroxidation products increased significantly compared to normoxic controls. Indomethacin pretreatment prevented the hypoxia-induced increase in membrane lipid peroxidation products but had no effect on the decrease in Na+, K+-ATPase activity. Thus the apparent reduction in free radical production by indomethacin pretreatment did not prevent the hypoxia-induced change in Na+, K+-ATPase activity.
Prospective, Randomized, Controlled Evaluation of a Gentamicin Loading Dose in Neonates
Authors: Semchuk Wm. , Shevchuk Y.M. , Sankaran K. , Wallace S.M.
Published: October 2009

A prospective, randomized, controlled evaluation comparing a 4-mg/kg loading dose (LD) of gentamicin to the standard regimen of 2.5 mg/kg every 12, 18 or 24 h was conducted in critically ill neonates. The objective of the study was to compare the time required to achieve a therapeutic peak serum concentration (i.e. the number of dosing intervals) and to compare the number of serum concentrations outside the therapeutic range as an indicator of potential toxicity between the treatment groups. Eighteen of 26 patients, 5 of 13 in the control group and 13 of 13 in the LD group (p = 0.012) achieved an initial peak concentration of > 5 μg/ml following the first gentamicin infusion. There were no significant differences between the control and LD group in the number of potentially toxic serum concentrations. When patients were subdivided according to gestational age (GA), patients of < 34 weeks had significantly lower initial peak concentrations. A LD of 4 mg/ kg in neonates, particularly those of < 34 weeks GA, produced a therapeutic peak concentration following the initial dose. There is a minimal risk of attaining serum concentrations commonly associated with toxicity providing the dosage interval is adjusted based on serum creatinine determinations. Based on this study, infants of > 34 weeks GA generally achieve therapeutic peak concentrations after the first dose with conventional dosing; however, in younger infants an appropriate LD is required to reach therapeutic concentrations early in therapy.
The Presence of Prolidase Activity in Amniotic Fluid and Its Evaluation as a Maturity Test
Authors: Gürdöl Figen , Genç Sema , Yalçin Önay , Gültepe Mustafa
Published: October 2009

Prolidase (EC: 3.4.13.9) catalyses the hydrolysis of the peptide bond involving the imino nitrogen of proline or hydroxyproline. Because of the high proportion of imino acids in collagen, this enzyme plays an important role in its degradation. Since collagen turnover rate is expected to be high during fetal growth, the level of prolidase activity may reflect the degree of fetal maturation. In this study, amniotic fluid prolidase I activity was measured in term and preterm pregnancies. Lecithin concentration, which has been widely used for predicting fetal lung maturity, was also measured. Prolidase I activity was positively correlated with lecithin levels (n = 30; r = 0.42; p < 0.02), and also with birth weight of the babies (n = 30; r = 0.52; p < 0.01) in the term-mature group. Dysmature babies had significantly lower prolidase I activity in the amniotic fluid which was thought to be indicative of growth retardation.
Perinatal Factors and 2-Year Minor Neurodevelopmental Impairment in Low Birth Weight Infants
Authors: Spinillo Arsenio , Fazzi Elisa , Orcesi Simona , Accorsi Patrizia , Beccaria Francesca , Capuzzo Ezio
Published: October 2009

Perinatal factors were investigated in 53 low birth weight infants with minor neurodevelopmental dysfunction at 2-year follow-up and in 106 consecutive controls matched for gestational age and birth weight (within 100-gram intervals). The obstetrical history, as evaluated by the obstetrical optimality score, was significantly worse in the cases than in controls (obstetrical optimality score = 50.9 ± 5.9 vs. 53.2 ± 6.9, p = 0.019 by Mann-Whitney test). Multiple conditional logistic regression analysis showed that after adjustment for socioeconomic status and education of the mother, a low number ( < 3) of prenatal visits, and a third trimester hemorrhage were the only antenatal factors significantly associated with an increased risk of minor infant neurodevelopmental impairment. Neonatal acidosis (pH < 7.2 in the first 24 h of life) and male gender were additional significant perinatal risk factors. Only a few antenatal and perinatal factors are correlated with subsequent minor neurodevelopmental impairment in low birth weight infants.
Gastrointestinal and Pancreatic Hormones in the Human Fetus and Mother at 18–21 Weeks of Gestation
Authors: Adrian T.E. , Soltesz G. , MacKenzie I.Z. , Bloom S.R. , Aynsley-Green Al
Published: October 2009

Several gastrointestinal hormones appear to play an important developmental role in the newborn, particularly in preterm neonates. Although the cells producing these peptides develop towards the end of the first trimester, fetal secretion of these regulatory peptides has not hitherto been demonstrated. Using samples collected by fetoscopy at 19–21 weeks of gestation we have measured concentrations of several gastrointestinal and pancreatic hormones. Maternal venous and amniotic fluid hormone concentrations were measured simultaneously. Concentrations of the pancreatic hormones, insulin, glucagon and pancreatic polypeptide (PP) were similar in fetal and maternal blood. Gastrin and motilin were present in the fetal circulation but at about 30% (p < 0.05) and 60% (p < 0.01) of the maternal levels, respectively. In contrast, enteroglucagon concentrations were more than twofold higher in the fetal circulation compared with maternal levels (p < 0.05). Concentrations of gastric inhibitory polypeptide (GIP) in fetal blood were higher than levels in maternal blood but not significantly. Concentrations of GIP (p < 0.001) were higher in the amniotic fluid than the fetal circulation. Gastrin and glucagon levels were similar in amniotic fluid and fetal blood. In contrast, PP and motilin were present in amniotic fluid, but at lower concentrations than in fetal blood. Enteroglucagon was not detectable in amniotic fluid. In conclusion, several alimentary hormones are secreted in the fetus at midterm. Since these peptides have trophic, secretory and motor effects on the gut, it is likely that these regulatory peptides are involved in the functional development of the fetal intestine.
Oxygen Saturation in Premature Neonates with Bronchopulmonary Dysplasia in a Hammock
Authors: Zanardo Vincenzo , Trevisanuto Daniele , Dani Carlo , Bottos Michele , Guglielmi Alberto , Cantarutti Felice
Published: October 2009

Premature neonates with bronchopulmonary dysplasia (BPD) frequently present borderline hypoxemia and the risk for oxygen desaturation may increase in relation to the posture. Our aim was to see if infants with BPD experience severe hypoxemia (SaO2 < 85%) in a hammock, a ‘containing’ posture considered advantageous to neuromotor and relational development of the preterm. Fifteen pulse oximetry recordings (Ohmeda B105 3760 Pulse Oximeter) were obtained in 15 subjects (range of gestational age and postnatal age 27–30 and 33–48 weeks, respectively; range of birth weight and body weight at entrance to the study 0.64–1.35 and 0.97–2.24 kg, respectively) before, during and after placement in a hammock; each testing period lasted 15 min, and each baby served as his or her own control. BPD preterm infants were receiving oxygen therapy by continuous flow standard nasal cannulas (FiO2 > 25%, < 40%). The analysis of the data, that have a rough gaussian distribution, indicates a worsening of SaO2 in the hammock position. In fact, mean ± SEM, median and range of the SaO2 values in pre- and posthammock position are comparable, but are significantly different at 99.9% confidence level (CL) in prehammock vs. hammock posture and at 98% CL in posthammock vs. hammock posture. Moreover, the percent of time with SaO2 < 85% during the periods recorded increased about 10 ± 5% in a hammock (24 ± 4%), in comparison to pre- (14 ± 3%) and posthammock position (15 ± 3%). These results suggest that oxygen-dependent BPD preterm infants in the hammock posture may experience severe hypoxemia that in part limits the possible advantages of the ‘containment’.
Elastase Given Intracisternally Opens Blood-Brain Barrier in Newborn Piglets
Authors: Temesvári Peter , Ábrahám Csongor S. , Gellén, Jr. János , Speer Christian P. , Kovács József , Megyeri Pál
Published: October 2009

The effect of elastase on the blood-brain barrier (BBB) permeability was intravitally studied by fluorescence photomacroscope using the open cranial window technique in newborn piglets. Eleven animals (group 1) were given intracisternal injection of porcine elastase (1.0 μg), while 7 piglets served as controls (group 2). Elastase administration resulted in spotty sodium fluorescein (MW 376 daltons) extravasations in pial venules in all animals of group 1 78 ± 4 min (mean ± SEM) after the challenge, and in a 2-fold increase (p < 0.05) in brain sodium fluorescein uptake both in occipital cortex and white matter. The concentration of elastase-α1-proteinase inhibitor complex increased significantly (p < 0.05) in cerebrospinal fluid samples in group 1 2 and 4 h after the inject; m, while it did not change in sera. A significant pleocytosis and leukocytosis was also seen in group 1 while there was no change in laboratory data and BBB remained tight in group 2. BBB permeability changes during neonatal meningitis may be caused, at least partially, by elastase.
Effect of Pentoxifylline on Nitric Oxide Released by Murine Macrophages
Authors: Lauterbach Ryszard , Grabowska Agnieszka , Marcinkiewicz Janusz
Published: October 2009

The growing knowledge on the pathological role of tumor necrosis factor α (TNF-α) and nitric oxide in septic shock stimulated efforts to control their generation pharmacologically in clinical stuations. Pentoxifylline (PTXF) is well known as an inhibitor of TNF synthesis, whereas information about its role in suppression of NO generation is much less available. In our study, we have shown that PTXF suppresses the synthesis of both mediators, TNF and NO, released by macrophages activated with different stimuli. However, in contrast to N-monomethyl-L-arginine (an inhibitor of NO synthase), PTXF influenced NO generation only during the induction phase. In conclusion, we suggest that a possible new therapeutic approach in septic shock may result from the inhibition of these two major mediators by simultaneous application of PTXF and a specific inhibitor of NO generation. Further experimental investigations and clinical trials are necessary to evaluate the safety and effectiveness of application of these inhibitors.
Embryogenesis in vitro: Study of Differentiation of Embryonic Stem Cells
Authors: Dushnik-Levinson Matat , Benvenisty Nissim
Published: October 2009

Embryogenesis is the fundamental process of differentiation of all tissues from a fertilized egg. This process involves establishment of distinct stem cells that will later differentiate to all cell types. Recently, lines of embryonic stem cells have been established in culture from blastocysts. The cells are pluripotent and can differentiate in vivo to all lineages. Interestingly, differentiation of these cells can also be induced in vitro. Morphological and molecular events that are characteristic of the development of the embryo can be mimicked in vitro by growing the cells under controlled conditions. Furthermore, the process of early development can now be studied and manipulated in vitro and specific lineages of stem cells can be obtained and grown in culture.
Oxygen Saturation during and after Feeding in Healthy Term Infants
Authors: Hammerman Cathy , Kaplan Michael
Published: October 2009

In instrumented infants, ‘normal’ feeding occasionally causes respiratory changes, however, the extent of ‘acceptable’ oxygen desaturation is undocumented. We studied O2 saturation in healthy full-term neonates under totally natural feeding conditions unencumbered by any mechanical devices. Infants’ O2 saturation was monitored continuously for 10 min of nutritive sucking and for 5 min after feeding. Twenty-one infants were studied, including 11 breast- and 10 bottle-fed infants. The distribution of saturation measurements was calculated and compared during feed vs. postfeed periods for both groups of infants. None of the infants had decreased saturation with feeding when compared to the pre feeding baseline. However, most of the infants in both groups did experience significantly lower O2 saturations after than during feeding (18 and 29% of the postfeed readings were < 90% in breast- and bottle-fed infants). Mean O2 saturations dropped from 96 ± 2% (during feed) to 93 ± 2% (postfeed) in breast-fed and from 95 ± 2% (during feed) to 92 ± 4% (postfeed) in bottle-fed infants. These findings elucidate the physiology of normal infant feeding and should be taken into account when monitoring term infants with oxygen saturation.
Maternal Dietary Carbohydrate Restriction Influences the Developmental Profile of Postnatal Rat Brain Indoleamine Metabolism
Authors: Koski Kristine G. , Lanoue Louise , Young Simon N.
Published: October 2009

Dietary glucose restriction during pregnancy can retard fetal brain development, lower term brain glycogen levels and adversely affect the serotonergic neurotransmitter system in the fetus. To study if the postnatal profile of brain indoles continues to respond to these diet-induced changes, pregnant rats were fed graded levels (0, 12, 24, 60%) of glucose from impregnation to day 15 postpartum, and neonatal brain measurements were made. A steady decrease in tryptophan levels, a steady increase in 5-hydroxytryptamine (5-HT) levels and a U-shaped change in 5-hydroxyindoleacetic acid (5-HIAA) were observed during the first 15 postpartum days. Superimposed on these development profiles was a temporary surge in the concentrations of all three indoles 24 h after birth, which was dramatic for tryptophan and more modest for 5-HT and 5-HIAA. The level of carbohydrate in the maternal diet significantly influenced the magnitude of this increase in tryptophan, 5-HT and 5-HIAA at 24 h: the values were significantly higher in the carbohydrate-restricted (12 or 24%) rat pups when compared with control or carbohydrate-free (0% glucose) offspring. No effects of dietary treatment were apparent by day 6. However, the reemergence of a significant difference in brain 5-HT content at day 15 postpartum indicates that even when energy intake is adequate the level of carbohydrate in the maternal diet may continue to play a role in modulating serotonergic neurotransmitter levels later in development.
Effect of Intrapartum Meperidine on Behavior of 3- to 12-Month-Old Infant Rhesus Monkeys
Authors: Golub Mari S. , Donald James M.
Published: October 2009

Potential long-term effects of intrapartum meperidine were studied in rhesus monkey infants whose dams received 0,2, or 3 mg/kg meperidine, i.v., during labor (n = 5, 5, 3). Spontaneous behavior and cognitive performance were evaluated at 3–12 months of age. Observation of spontaneous behaviors indicated less age-related increase in quiet activities in drug-exposed infants. In the discrimination reversal test, drug-exposed infants had more balks (p = 0.008) and fewer correct choices (p = 0.008) during initial phases of the first reversal. Due to sex differences in the delayed alternation test, evaluation of drug effects on short-term memory was not possible. In the continuous performance test, drug-exposed infants performed better (NS) and had fewer omission errors (p = 0.034) during the second half of the test period. These initial findings suggest that short-term opiate exposure during labor can alter later behavior of infant monkeys.
Maternal-Fetal Folate Status and Neural Tube Defects: A Case Control Study
Authors: Bunduki V. , Dommergues M. , Zittoun J. , Marquet J. , Muller F. , Dumez Y.
Published: October 2009

The object of this study was to explore the role of folate in the pathophysiology of neural tube defects (NTD). Maternal and fetal serum and red blood cell folate were assayed in 14 cases of NTDs and compared with 14 controls with other malformations and matched for gestational age (range 18–36 weeks). In mothers of NTD fetuses, serum folate (5.2 ng/ml), red blood cell folate (294 ng/ml) and the folate methylation rate (65%) were significantly lower than in controls (6.6 and 399 ng/ml, respectively, and 77%). However, the fetal folate status was similar in cases and controls. In the NTD group, folate metabolism was altered in the mothers but not in the fetuses. Therefore, a normal folate placental transfer can be assumed in this group. In addition, it could be speculated that decreased maternal folate methylation might be involved in the pathogenesis of NTDs.
Obstetric Risk Factors Affecting Incidence of Low Birth Weight in Live-Born Infants
Authors: Abdulrazzaq Yousef M. , Bener Abdulbari , Dawodu Adekunle , Kappel Inge , Surouri Farouk Ahmed , Varady Elizabeth , Liddle Larry , Varghese Mani , Cheema M.Y.
Published: October 2009

This study was conducted to determine the incidence of low birth weight (LBW) in the indigenous population of Al Ain and to identify some risk factors associated with it. The population studied included all consecutive deliveries, occurring in the 3 hospitals in Al Ain City, where almost all deliveries take place, during a 1-year period. When a LBW infant (< 2,500 g) was born, gestational age assessment was made and a questionnaire completed during an interview with the mother. For control, the first baby who weighed more than 2,500 g at birth, following the birth of a LBW was recruited. It was found that a total of 3,485 live births occurred of which 293 were classified as LBW, giving an LBW incidence of 8.4%. Of these, 73 (24.9%) were small for gestational age ( < 10th percentile for gestational age). Overall, the mothers of LBW infants were found to be statistically significantly younger in age. The mothers of LBW infants also had a significantly higher number of previous LBW deliveries, twin deliveries and a larger number of premature rupture of membranes. The factors that were not significantly different in the 2 groups were diabetes during pregnancy, chronic hypertension, preeclampsia/eclampsia, occurrence of significant infection during pregnancy, 1st and 2nd trimester bleeding, and antepartum hemorrhage. This is the first comprehensive study on the incidence of LBW infants in the United Arab Emirates. The main obstetric factors responsible for this were found to be age, number of previous LBW babies, premature rupture of membranes and multiple births.
Effect of Hypoinsulinemia on Growth in the Fetal Rabbit
Authors: Chaffin David G. , Clark Richard M. , McCracken David , Philipps Anthony F.
Published: October 2009

Insulin is an important regulatory hormone in the control of fetal growth. In a fetal rabbit model, a non-ruminant species, the effects of insulin deprivation on glucose, growth and protein metabolism were studied. The fetuses of 10 pregnant New Zealand white rabbits in one uterine horn received a subcutaneous injection on day 25 of gestation (term = 30 days) of 0.1 mg streptozotocin (STZ)/gm fetal weight. The fetuses in the opposite horn received a sham injection of buffer. The dams were then killed on day 29. The fetal insulin concentration was depressed by 38%, and the serum glucose concentration was elevated by 28% in animals given STZ when compared to control animals. Fetal weights, carcass weights and skeletal growth, as measured by crown-rump length and tibial length of STZ-treated fetuses, were significantly reduced by 7–13%. However, organ weights were not significantly different, except for the kidneys which were 17% lighter. Protein and mineral contents of the carcasses were also reduced compared to the control fetuses. Thus, insulin deprivation in fetal rabbits results in significant growth impairment in a pattern similar to that of human asymmetric intrauterine growth retardation.
Lack of Production and Growth-Modulating Effects of 1α,25-Dihydroxyvitamin D3 in Cultured Fetal Rat Hepatocytes
Authors: Partyka C.M. , Gelardi N.L. , Fadden K. , Rifai A. , Gruppuso P.A. , Oh W. , Reddy G.S.
Published: October 2009

1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the hormonal form of vitamin D3, has been shown to play a role in the regulation of growth of the regenerating adult rat liver following partial hepatectomy. In addition, a recent study implicated the neonatal liver as a possible extrarenal site of 1,25(OH)2D3 synthesis. Therefore, in our present study we used rapidly growing fetal hepatocytes in culture as a model cell line for regenerating hepatocytes and tested the hypothesis that fetal hepatocytes locally produce 1,25(OH)2D3 which in turn regulates their growth. Hepatocytes isolated from 19-day rat fetuses were grown in culture for 24 h in minimal essential medium without added serum or mitogens. To identify 1,25(OH)2D3 production, we incubated fetal hepatocytes in culture with 3H-25-hydroxyvitamin D3 (3H-25-OH D3) for 2,6 and 24 h. High-pressure liquid chromatographic analysis of the lipid extract of the medium and cells revealed no evidence of conversion of 3H-25-OH D3 into 3H-1,25(OH)2D3. Additionally, to investigate the effect of 1,25(OH)2D3 on DNA synthesis in fetal liver, we measured 3H-thymidine incorporation by the cultured fetal hepatocytes following 24 h of exposure to various concentrations of 1,25(OH)2D3. The results of DNA synthesis revealed no effect of 1,25(OH)2D3 on fetal hepatocyte growth. As alterations in growth regulation by 1,25(OH)2D3 in other cells are thought to be mediated by intracellular vitamin D receptors (VDR), the expression of the VDR message in the fetal and maternal tissues of a pregnant rat was studied. RNA was first isolated from fetal liver, fetal kidney, maternal liver and maternal kidney, and the corresponding cDNA was then generated by reverse transcription. The cDNA for VDR was amplified by PCR using oligonucleotide primers specific for the rat VDR sequence. A minor PCR product DNA for VDR in fetal liver was detected compared to the level of expression in fetal kidney and maternal liver and kidney. The low level of VDR expression in fetal liver may explain the lack of sensitivity of fetal hepatocyte DNA synthesis to 1,25(OH)2D3. In summary, our data suggest that in the fetal rat liver, 1,25(OH)2D3 is not locally produced and does not modulate DNA synthesis.
Acute Entry of Bilirubin into Rat Brain Regions
Authors: Ruud Hansen Thor Willy
Published: October 2009

In kemicterus bilirubin appears at higher concentrations in the basal ganglia, the cerebellum, and the medulla. The mechnism for this distribution is unknown, but might involve differences in bilirubin entry among brain regions. We infused [3H]bilirubin (30 mg/kg over 5 min) intravenously into young Sprague-Dawley rats (n = 21, weight 144 ± 10 g, mean ± SD). Blood was sampled from the tail, and groups of rats were killed at 15, 30, 45, 60, and 75 min by intravenous pentobarbital. After in situ flushing of the brain vasculature, the brain was dissected into seven regions, each of which was weighed, dissolved in Soluene-350, and subsequently scintillation counted. Blood samples were analyzed for bilirubin (including specific activity), albumin, and blood gases. Brain bilirubin concentrations in each of the regions were calculated by comparing the radioactivity in that region with the specific activity of bilirubin. Using a curve-fitting program (EXPOFIT), the concentrations of bilirubin in each brain region at 5 min (i.e. the end of bilirubin infusion) could be estimated, and were as follows (nmol/g ± SD): cortex 6.4 ± 4.4; hippocampus 6.2 ± 3.3; striatum 6.3 ± 4.5; midbrain 7.3 ± 4.4; hypothalamus 6.3 ± 4.6; cerebellum 6.7 ± 4.1, and medulla 7.0 ± 4.0. There were no significant differences in the bilirubin concentrations between brain regions (F6 140 0.205). The mechanism for preferential localization of bilirubin to the basal ganglia probably does not involve the acute entry of bilirubin into brain.
Does Endothelin-1 Mediate the Hypoxemia-lnduced Renal Dysfunction in Newborn Rabbits?
Authors: Semama D.S. , Thonney M. , Guignard J.-P.
Published: October 2009

In the newborn rabbit, acute normocapnic hypoxemia increases the renal vascular resistance, leading to renal hypoperfusion and decreased glomerular filtration rate. Endothelin is a potent vasoconstrictor peptide, produced by vascular endothelial cells, which could play a role as a mediator of the hypoxemia-induced renal dysfunction. To test this hypothesis, experiments were performed in 24 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glomerular filtration rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 newborn rabbits (group 1), a bolus injection of 5 nmol·kg––1 of endothelin caused a marked increase in mean blood pressure and renal vascular resistance leading to a significant fall in glomerular filtration rate (––12 ± 4%) and renal blood flow (––16 ± 3%). A second group of animals (n = 8) confirmed the neutralizing activity of the endothelin-1 antiserum in vivo. In spite of pretreatment with endothelin-1 antiserum, hypoxemia induced an increase in renal vascular resistance (+40 ± 18%; p < 0.05) associated with a significant fall in glomerular filtration rate (––18 ± 7%) and renal blood flow (––29 ± 6%) in 8 newborn rabbits (group 3). The present results suggest that endothelin-1 does not mediate the hypoxemia-induced renal changes.
Acute Respiratory Failure Mediated by Reactive Drug Metabolites
Authors: Murphy David , Kronick Jonathan B. , Rieder Michael J.
Published: October 2009

Reactive drug metabolites have been implicated in the pathogenesis of adverse reactions to the aromatic anticonvulsants. A patient presented with a hypersensitivity reaction to the aromatic anticonvulsants which evolved into Stevens-Johnson syndrome and was complicated by the presence of adult respiratory distress syndrome. When the patient’s cells were tested for sensitivity in vitro to reactive metabolites of the aromatic anticonvulsants, they were markedly more sensitive to metabolites of the aromatic anticonvulsants than were the cells of controls (p < 0.05). The adult respiratory distress syndrome has not previously been described as a complication of hypersensitivity reactions to the aromatic anticonvulsants. In vitro testing also demonstrated cross-sensitivity to the anticonvulsants, allowing selection of a therapeutic regimen which would not be associated with a risk of exacerbating the hypersensitivity reaction.
Metabolism of Chloramphenicol by Glutathione S-Transferase in Human Fetal and Neonatal Liver
Authors: Holt Daphne E. , Hurley Rosalinde , Harvey David
Published: October 2009

The glutathione S-transferases of human fetal and neonatal liver catalyse the conjugation of glutathione with chloramphenicol at a low but measurable rate. The highest rates were 1.30 nmol/min/mg protein in a preterm neonate of 26 weeks of gestation and 1.11 nmol/min/mg in a fetus of 22 weeks of gestation, while the lowest measurable was 0.1 nmol/min/mg in a fetus of 17 weeks of gestation. The activity did not correlate with gestational age, but appeared dependent on the concentration of glutathione in the reaction mixture. The rate rose by a factor of three, from 0.39 nmol/min/mg protein with no added glutathione to 1.24 nmol/min/mg with 2 µmol/ml added to the reaction mixture. Chloramphenicol-aldehyde was detectable in the reaction mixture when a liver extract was incubated with glutathione but the proposed intermediate, glutathione-chloramphenicol, could not be demonstrated. Differences in activity with chloramphenicol or a model substrate, under varying conditions, indicate that different isoenzymes are concerned with the conjugation of glutathione to the two substrates. These data support the hypothesis that when glucuronide conjugation is depressed by immaturity, chloramphenicol is metabolised via other pathways.
Intestinal Transport and Processing of Immunoglobulin G in the Neonatal and Adult Rat
Authors: Benlounes N. , Chedid R. , Thuillier F. , Desjeux J.F. , Rousselet F. , Heyman M.
Published: October 2009

The proximal intestine of neonatal rats expresses a specific receptor (RFcn) that binds immunoglobulin G (IgG) and is no longer expressed after weaning. The aim of this study was to quantify and compare the intestinal transport and processing of IgG in intestinal fragments with or without RFcn, with the fluid-phase transport of horseradish peroxidase (HRP). The mucosal to serosal transport and degradation of IgG and HRP were measured in neonatal and adult rats in vitro in Ussing chambers. IgG transcytosis occurred without degradation in the proximal intestine of neonatal rats, where RFcn is expressed, up to a luminal concentration of 300 μg/ml. At higher mucosal IgG concentrations, a degradative pathway was also involved. The immunoreactive IgG fluxes across the proximal intestine of neonatal rats were higher than those observed in the distal neonatal intestine or those in the proximal and distal adult intestine. The rate of HRP transcytosis was higher than that of IgG but it involved a mainly degradative pathway. These results suggest that in the proximal intestine of the neonatal rat, where RFcn is expressed, the transcytotic rate for IgG is not increased, but the nondegradative transport of immunoreactive IgG is favored, especially at low luminal concentrations.
Functioning of the Porcine Pituitary-Adrenocortical Axis during Neonatal Development
Authors: Klemcke Harold G. , Brown-Borg Holly M. , Borg Kurt E.
Published: October 2009

A study was conducted with neonatal boars to measure age-related changes in functioning of the pituitary-adrenocortical axis. Pigs were randomly assigned to control (n = 7–10/age) or treated (1-min restraint, n = 9–11/age) groups to be sampled at either 12, 19, or 26 days of age. Blood samples were taken via catheter 10 min before and 3, 10, and 20 min after restraint or at similar time intervals in controls. One day later, pigs were killed and adrenal glands obtained for ACTH receptor measurements. Basal plasma ACTH concentrations were greatest (p = 0.035) on day 12 when compared with later ages, but basal plasma cortisol concentrations were comparable at the three ages. Compared with controls, restraint elevated incremental plasma ACTH and cortisol responses at each age (p < 0.004). On day 12, maximal plasma ACTH (p = 0.0006) and incremental cortisol (p < 0.006) responses to restraint were greater than at later ages. Binding to adrenal ACTH receptors was greatest (p < 0.05) at day 13, which may help explain the apparently increased in vivo response of the adrenal gland to ACTH at this time. Restrained pigs had increased growth rates with increasing age (p = 0.016) whereas growth rates for control pigs did not differ with age. At day 27, 24 h after the 1-min restraint, body weights of restrained pigs exceeded those of control pigs (p = 0.045). At day 20, adrenal DNA and protein in pigs restrained 24 h previously were greater than in control pigs (p < 0.05). These data suggest age-related changes in functioning of the pituitary-adrenal axis in neonatal boars, and an absence of a period during neonatal life when the porcine pituitary adrenocortical axis cannot respond to a stressor. The data also indicate both rapid and long-term responses of the adrenal to a very modest stressor and suggest an extreme sensitivity of neonatal pigs to environmental perturbations.
Endothelin 1-21 Plasma Concentrations on Days 1 and 4 of Life in Healthy and III Preterm Neonates
Authors: Malamitsi-Puchner Ariadne , Economou Emmanuel , Efstathopoulos Theodore , Sevastiadou Sophia , Hadzistamatiou Zoe , Nicolopoulos Dimitrios
Published: October 2009

Endothelins (ETs) are highly vasoconstrictive 21-amino acid peptides possessing also cell-proliferative properties. They have been implicated in a variety of perinatal pathologic conditions, and their plasma concentrations have been found elevated in humans at birth. The purpose of this study was to determine ET 1-21 plasma concentrations in healthy and ill preterm infants and to investigate possible concentration changes with time from birth in cases of normal and abnormal adaptation to extrauterine life. The study comprised 36 preterm infants. Twenty-eight, comprising group A, were healthy (22/28) or minimally affected (6/28) and 8, comprising group B, were moderately (2/8) or severely ill (6/8) requiring continuous positive airway pressure or intermittent positive pressure ventilation as well as surfactant administration. All infants in group B had intraventricular hemorrhage grade ≥ II. Venous blood from all neonates was drawn on days 1 and 4 and ET 1-21 plasma concentrations were determined by radioimmunoassay (Amersham kit RPA 5559). ET 1-21 plasma concentrations were on day 1: 16.25 ± 8.14 and 21.81 ± 5.87 and on day 4: 12.89 ± 4.56 and 16.16 ± 5.43 pmol/l, for groups A and B, respectively. The statistical analysis showed a significant reduction in plasma ET concentrations on day 4 in both groups (p = 0.009 and p = 0.025, respectively). Nevertheless, ET 1-21 plasma concentrations were on day 4 significantly higher in ill preterm infants presenting symptoms from tissues involved in the elimination of ETs from the circulation as well as in their production.
Profile of Alveolar Gases during Periodic and Regular Breathing in Preterm Infants
Authors: Pereira Manuel R. , Reis Francisco C. , Landriault Leanne , Cates Donald B. , Rigatto Henrique
Published: October 2009

To determine the changes in alveolar PCO2 (PACO2) and PO2 (PAO2) during periodic and regular breathing epochs in the same infants, we studied 11 preterm infants during quiet sleep (birth weight 1,630 ± 94 g; gestational age 31 ± 1 weeks; postnatal age 32 ± 3 days). A total of 94 breathing/apneic cycles were analyzed and compared with regular periods. During periodic and regular breathing epochs, there were negative correlations of PAO2 on PACO2. Short (5 s) and long ( > 5 s) apneas for individual infants occurred along the regression line for that infant. There was not a single overall critical PACO2 below which apnea occurred, but for individual infants the PACO2 and the PACO2 of the breath preceding apnea varied within a limited range. Apneas occurred in clusters of PACO2 and PAO2 along the average regression line of PAO2 on PACO2. Analysis of the data showed that apnea occurred at the lowest PACO2 and highest PAO2 levels if allowance was made for circulation time. During apnea, ‘the best fit’ for the increase in PACO2 and the decrease in PAO2 was linear, rather than logarithmic. The findings suggest the following. (1) There is not a single overall critical level of PACO2 for apnea to occur, but in a given infant this level varies within a limited range. This indicates that these infants are likely breathing near the apnea threshold. (2) Short and long apneas appear to occur randomly along the regression of PAO2 on PACO2 for a particular infant. (3) The changes in alveolar gases are linear during apnea. The data are consistent with the idea that each infant has an optimum narrow range of PACO2 and PAO2 values in which apnea occurs.