bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Recovery in the Avian Ear after Hair Cell Regeneration
Authors: Smolders Jean W.Th.
Published: April 2003

Trauma to the inner ear in birds, due to acoustic overstimulation or ototoxic aminoglycosides, can lead to hair cell loss which is followed by regeneration of new hair cells. These processes are paralleled by hearing loss followed by significant functional recovery. After acoustic trauma, functional recovery is rapid and nearly complete. The early and major part of functional recovery after sound trauma occurs before regenerated hair cells become functional. Even very intense sound trauma causes loss of only a proportion of the hair cell popu- lation, mainly so-called short hair cells residing on the abneural mobile part of the avian basilar membrane. Uncoupling of the tectorial membrane from the hair cells during sound overexposure may serve as a protection mechanism. The rapid functional recovery after sound trauma appears not to be associated with regeneration of the lost hair cells, but with repair processes involving the surviving hair cells. Small residual functional deficits after recovery are most likely associated with the missing upper fibrous layer of the tectorial membrane which fails to regenerate after sound trauma. After aminoglycoside trauma, functional recovery is slower and parallels the structural regeneration more closely. Aminoglycosides cause damage to both types of hair cells, starting at the basal (high frequency) part of the basilar papilla. However, functional hearing loss and recovery also occur at lower frequencies, associated with areas of the papilla where hair cells survive. Functional recovery in these low frequency areas is complete, whereas functional recovery in high frequency areas with complete hair cell loss is incomplete, despite regeneration of the hair cells. Permanent residual functional deficits remain. This indicates that in low frequency regions functional recovery after aminoglycosides involves repair of nonlethal injury to hair cells and/or hair cell-neural synapses. In the high frequency regions functional recovery involves regenerated hair cells. The permanent functional deficits after the regeneration process in these areas are most likely associated with functional deficits in the regenerated hair cells or shortcomings in the synaptic reconnections of nerve fibers with the regenerated hair cells. In conclusion, the avian inner ear appears to be much more resistant to trauma than the mammalian ear and possesses a considerable capacity for functional recovery based on repair processes along with its capacity to regenerate hair cells. The functional recovery in areas with regenerated hair cells is considerable but incomplete.
Mechanics of the Middle Ear System: Age-Related Changes in Viscoelastic Properties
Authors: Gaihede Michael , Koefoed-Nielsen Birger
Published: April 2003

Morphological studies of age-related changes in the tympanic membrane have suggested a decreased elasticity for increasing age, whereas age-related changes in admittance measured by tympanometry have revealed inconsistent results. In this study we report on the viscoelastic properties of the middle ear system by means of a new method in two different age groups. This method measures hysteresis (μJ), which describes the viscous properties of the system, and compliance (mm3/kPa) reflecting its elasticity. Moreover, Pec0 (kPa) was recorded, which corresponds to middle ear pressure measured by tympanometry. Recordings were made in a group of 30 older normal subjects (mean age 77 years) and results were compared to previous findings in a group of 39 younger normal subjects (mean age 29). Hysteresis was markedly decreased in the older normal group compared to the younger one (p = 0.057). This may reflect morphological changes previously reported in the tympanic membrane and can be related to theoretical considerations on tympanic membrane rupture pressures. Compliance and Pec0 were not influenced by variation in age (p = 0.645 and 0.966).
Coma Outcome Prediction Using Event-Related Potentials: P3 and Mismatch Negativity
Authors: Kane Nicholas M. , Butler Stuart R. , Simpson Tom
Published: April 2003

The prediction of the outcome from coma is of considerable importance to the patients, their relatives and attendant medical staff, and yet current clinical methods lack sensitivity and specificity. Objective investigations can enhance the accuracy of such predictions and are an important adjuvant when reaching decisions to continue or terminate life support. Of the neurophysiological methods available, electroencephalography and short-latency somatosensory evoked potentials have proved the most useful in the clinical setting. These tests are good predictors of an adverse outcome; however, they tell us only about the ongoing cerebral activity and integrity of the primary somatosensory pathways, respectively. The presence of long-latency event-related potentials has been shown to be a useful predictor of a favourable neurological outcome, and thus their use complements other neurophysiological techniques. Their potential application in clinical practice is reviewed.
Mismatch Negativity and N100 in Comatose Patients
Authors: Fischer Catherine , Morlet Dominique , Giard Marie-Hélène
Published: April 2003

Mismatch negativity (MMN) and N100 auditory evoked potential were recorded in 52 healthy subjects and in 128 severely comatose patients. The MMN was present in 33/128 patients and N100 in 84/128. A ratio of 30/33 patients with MMN and 70/84 with N100 regained consciousness in a mean time of 6.3 ± 4 days after the recording session. Thus, in terms of predicting return to consciousness, the MMN was more specific (90.9%) than the N100 (57.6%), but its sensitivity was lower (31.6% for MMN and 73.7% for N100, respectively). The amplitudes of MMN and N100 in comatose patients were smaller than those of healthy subjects. It is concluded that MMN and N100 can be very useful in predicting whether or not a comatose patient will regain consciousness.
Unilateral Neglect after Right-Hemisphere Damage: Contributions from Event-Related Potentials
Authors: Deouell Leon Y. , Hämäläinen Heikki , Bentin Shlomo
Published: April 2003

Unilateral neglect is a frequent sequel of right-hemisphere damage. Patients suffering from neglect may fail to detect, orient to, acknowledge or respond to stimuli on their contralesional side, even in the absence of primary sensory or motor loss. Despite the major clinical significance of the phenomenon and its potential implications for our understanding of human cognition, the underlying cognitive deficits are not well understood. We review the relatively few event-related potential studies that attempted to assess the different parts of the cognitive system in neglect patients. We suggest that theories of neglect, based primarily on performance data, may be refined by incorporating these results, and that this line of research may provide information that is not available using traditional performance measures.
Purkinje Cell Impairment Induced by Early Movement Restriction
Authors: Pascual Rodrigo , Hervias María C. , Tohá María E. , Valero Antoni , Figueroa Héctor R.
Published: April 2003

In the present work the effects of movement restriction imposed during the early postweaning period on both Purkinje cell dendritic development and exploratory behavior were analyzed. Male and female Sprague-Dawley albino rats were reared either in isolated-restricted or social-standard environments from postnatal day 18 to 30. On the 31st postnatal day, all rats were behaviorally evaluated by the open-field test and then sacrificed under deep ether anesthesia. Vermian cerebellar sections were later stained with the Golgi-Cox-Sholl method and the Purkinje cell dendritic morphology was quantified under light microscopy. The results indicate that early somatomotor restriction severely impairs both exploratory behavior and Purkinje cell dendritic growth.
Postnatal Somatic Growth and Insulin Contents in Moderate or Severe Intrauterine Growth Retardation in the Rat
Authors: Garofano Anna , Czernichow Paul , Bréant Bernadette
Published: April 2003

A rat model of perinatal malnutrition was designed to study the role of nutrition in postnatal somatic growth and insulin stores until adulthood. Maternal food restriction (50%) from day 15 of pregnancy resulted in intrauterine growth retardation (IUGR) in the offspring. The outcome of moderate or severe IUGR was investigated. Neonates with moderate IUGR normally nourished postnatally showed normal body and organ weights and normal insulin contents in adulthood. Offspring with severe IUGR normally nourished postnatally also rapidly recovered normal body and pancreatic weights, but liver and kidney weights were significantly reduced at adult age. Malnutrition until weaning in offspring with severe IUGR induced marked growth retardation (50%) in body and organ weights at weaning. Although pancreatic weight recovered at adult age, body, liver and kidney weights were irreversibly affected, despite several months of normal nutrition. Furthermore, severe IUGR at birth resulted in decreased insulin content at adult age, irrespective of postnatal nutrition. In conclusion, this animal model demonstrates that normalization of adult size can be dissociated from organ growth and also that altered insulin stores in adulthood are more dependent on the severity of IUGR at birth than on postnatal catch-up in organ growth.
Developmental Regulation of the Inhibitory Effect of Dopamine on Prolactin Release in the Preterm Neonate
Authors: Seri Istvan , Somogyvari Zsolt , Hovanyovszky Sarolta , Kiszel Janos , Tulassay Tivadar
Published: April 2003

The secretion and release of prolactin from the anterior pituitary is under the tonic inhibitory control of endogenous dopamine produced in the central nervous system. Exogenous dopamine inhibits prolactin secretion by reaching the pituitary via the portal circulation, and the hypolactotropic effect of dopamine infusion has been documented in all age groups in humans. However, the maturation of lactotroph sensitivity to dopaminergic inhibition has not been studied. Therefore, we followed the changes in serum prolactin concentrations before, during, and after dopamine infusion in 19 sick preterm infants with a mean gestational age of 30.6 ± 0.6 weeks during the first 3 days of life, and examined the relationship of the hypolactotropic effect of dopamine to gestational age and birth weight in this patient population. As expected, dopamine therapy resulted in a decrease in mean serum prolactin from 89.4 ± 9.5 to 58.6 ± 9.1 µg/l (p < 0.05) with a return of the serum prolactin concentration to the pretreatment level 2–6 h after discontinuation of drug administration (98.3 ± 11.7 µg/l, p < 0.05). However, simple regression analysis of the individual data revealed that the magnitude of the dopamine-induced decrease in serum prolactin was significantly influenced by gestational age (p = 0.006) and birthweight (p = 0.037). Thus, our findings provide evidence for the maturation of pituitary lactotroph sensitivity to dopaminergic inhibition in the preterm human neonate.
The Production of Pro- and Anti- Inflammatory Cytokines in Neonates Assessed by Stimulated Whole Cord Blood Culture and by Plasma Levels at Birth
Authors: Seghaye Marie-Christine , Heyl Wolfgang , Grabitz Ralph G. , Schumacher Kathrin , von Bernuth Götz , Rath Werner , Duchateau Jean
Published: April 2003

The capability of neonates to achieve cytokine balance was evaluated. Production of the pro-inflammatory cytokines TNFα and IL-8, of the natural anti-inflammatory cytokine IL10 and of the regulator of the acute phase response IL6 was assessed after whole blood stimulation by lipopolysaccharide in cord blood (n = 10), adult volunteers serving as control (n = 17). Additionally, circulating cytokines were determined in cord and in maternal blood immediately after delivery (n = 27, respectively). Significant production of TNFα, IL8, IL10 and IL6 was observed in cord blood after lipopolysaccharide stimulation and was similar to cytokine production in adult blood. The plasma concentrations of TNFα were significantly higher in cord than in maternal blood, while plasma concentrations of IL10 and IL6 were significantly lower. Our results demonstrate fully developed capability of whole cord blood to synthesize pro- and anti-inflammatory cytokines in response to a pro-inflammatory stimulation in vitro. In vivo, however, higher circulating TNFα and lower IL10 and IL6 levels in cord blood suggest that the inflammatory stress associated with normal delivery does not induce detectable anti-inflammatory response in neonates at birth.
Effect of Dietary n–3 Fatty Acids on Hypoxia-Induced Necrotizing Enterocolitis in Young Mice
Authors: Akisü Mete , Baka Meral , Çoker Işıl , Kültürsay Nilgün , Hüseyinov Afig
Published: April 2003

Necrotizing entercolitis (NEC) is an important neonatal disease with a high mortality rate. Inflammatory mediators, such as mainly platelet-activating factor (PAF), leukotrienes (LT) and tumor necrosis factor play an important role in the genesis of NEC. Diets in Ω–3 (n–3) fatty acids appear to have an antiinflammatory effect, which is thought to be due to decreased active prostaglandins and leukotrienes production after incorporation of these fatty acids into cell membrane phospholipids. We investigated the protective effect of fish oil (source of n–3 fatty acids) on hypoxia-induced model of NEC. Young mice were divided into three groups; group 1 mice were fed standard chow (n–3 fatty acids-free), group 2 was fed a chow supplemented by 10% fish oil for 4 weeks. Group 3 mice served as control. We examined the intestinal lesions by light microscopy and measured intestinal tissue PAF and LB4 levels in hypoxia-induced model of NEC. Significantly increased intestinal PAF and LTB4 levels were found in group 1 mice when compared to group 2 and group 3 mice. The histopathology of the intestinal lesions in group 1 animals was characteristic of ischemic injury. In the n–3 fatty acids-supplemented animals these lesions were milder. The present study shows that endogenously released PAF and LTB4 play an important role in mediating hypoxia-induced intestinal necrosis. The present study also suggests that dietary supplementation with n–3 fatty acids suppress intestinal PAF and LTB4 generation in hypoxia-induced bowel necrosis. The intestinal protective effect of n–3 fatty acids in an experimental model of NEC may open new insight into the treatment and preventation of NEC in neonates.
Pharmacodynamic Effects and Pharmacokinetic Profile of Continuous Infusion Fentanyl in Newborn Piglets
Authors: Rajan Vigna , Beharry Kay D.A. , Williams Paul , Modanlou Houchang D.
Published: April 2003

The objective of this study was to determine hemodynamic effects and pharmacokinetic profiles of fentanyl with continuous infusion in 1- to 3-day-old newborn piglets. The piglets (n = 6) were administered a loading dose of fentanyl at 30 µg/kg i.v. over 15 min followed by a continuous i.v. infusion at 10 µg/kg/h for 6 h. The control group (n = 8) received equivalent volume bolus and infusion of 5% dextrose. Blood samples were obtained serially from systemic circulation and sagittal sinus vein for measurement of plasma fentanyl, pH and blood gases. Plasma fentanyl achieved steady state levels by 30 min of infusion both in the systemic (202.7 ± 39.1 ng/ml) and sagittal sinus vein (136.7 ± 20.7 ng/ml). Fentanyl caused a transient increase in respiratory rate at 2 h. Heart rate was significantly elevated at 30 min and 6 h during infusion but systemic and sagittal sinus vein blood pressure remained unchanged. Systemic and sagittal sinus vein PO2 were significantly decreased from 2 through 6 h of infusion. Compared to the control group, there was a 56% (p < 0.01) decrease in sagittal sinus vein O2 content at 30 min of infusion, an effect which lasted up to 6 h (47%, p < 0.01). Fractional O2 extraction by the brain increased significantly at 30 min (26%, p < 0.01) and remained elevated throughout the infusion time (22%, p < 0.05 at 6 h). Brain fractional O2 extraction increased as a function of brain fractional fentanyl extraction (r2 = 0.40, p < 0.001). Mean clearance was estimated as 56.2 ± 13.7 ml/kg/h (range 43.5–76.9 ml/kg/h), mean volume of distribution at steady state was 1.29 ± 0.6 liters/kg (range 0.78–2.15 liters/kg) and the mean half-life was 15.7 ± 5.7 h (range 9.4–22.5 h). These data suggest that increased systemic oxygen may be necessary to maintain normal cerebral oxygen extraction during fentanyl anesthesia/analgesia.
Developmental Changes in the Calcium Sensitivity of Rabbit Cranial Arteries
Authors: Akopov S.E. , Zhang L. , Pearce W.J.
Published: April 2003

The present experiments examine developmental changes in cerebrovascular Ca2+ sensitivity. Common carotid (COM), basilar (BAS) and femoral (FA) arteries from adult (n = 16), 8- to 9-day-old (n = 15) and 24- to 25-day-old rabbits (n = 12) were denuded of the endothelium and permeabilized with β-escin. Bath calcium concentrations were controlled via EGTA-Ca2+ buffer solutions. Adult pCa-force relations were right-shifted relative to those of 8- to 9-day-old rabbits but were similar to those of 24- to 25-day-olds. Adult pD2 (–log ED50) values for Ca2+ averaged 6.36 ± 0.03 (COM), 6.77 ± 0.04 (BAS) and 6.40 ± 0.04 (FA). Corresponding 8- to 9-day-old values were 6.85 ± 0.03, 7.08 ± 0.08 and 6.76 ± 0.05. In all arteries studied, the addition of 5-hydroxytryptamine (5-HT) subsequent to contraction by a constant submaximal (EC30) concentration of Ca2+ produced a dose-dependent and GDPβS-sensitive increase in tension attributable to an increase in Ca2+ sensitivity. The magnitudes of 5-HT-induced increases in Ca2+ sensitivity were significantly greatest in 8- to 9-day-old rabbits, intermediate in 24- to 25-day-old rabbits, and least in adults. GTPγS mimicked the effects of 5-HT and prevented further increases in Ca2+ sensitivity induced by 5-HT in all arteries from all age groups. GDPβS completely reversed all effects of 5-HT on Ca2+ sensitivity. From these data we conclude that baseline Ca2+ sensitivity is elevated in newborn relative to adult rabbits, at least in femoral, common carotid and basilar arteries. In these arteries, 5-HT can increase Ca2+ sensitivity via a G-protein-dependent mechanism which is more effective in neonatal than adult arteries. These effects of maturation on vascular Ca2+ sensitivity may play an important role in developmental changes in vascular reactivity.
Protective Function of Proteins and Lipids in Human Milk
Authors: Hamosh Margit
Published: April 2003

Human milk provides the infant with protection against infectious diseases. This protection is conferred through several mechanisms: specific antibody targeted protection against pathogens in the infant’s environment (through milk IgA, IgG, and IgM) and broad-spectrum, nonspecific protection provided through several distinct mechanisms. These are: bactericidal effects (lactoferrin), bacteriostatic action (lactoferrin, lysozyme), lysis of microorganisms (lysozyme), antiviral effects (lactoferrin, products of milk fat digestion), antiprotozoan activity (free fatty acids produced during gastric and intestinal digestion of milk fat), and ligand action (inhibition of Helicobacter pylori adhesion to gastric mucosa by κ-casein). In addition to these protective functions of the proteins and lipids of human milk, several enzymes present in human milk might provide protection by generating components that are bactericidal (bile salt dependent lipase, peroxidase), prevent inflammatory reactions (platelet-activating factor acetylhydrolase), or protect the integrity of milk proteins (antiproteases).
Maturational Modification of Hypoxic Relaxation in Ovine Carotid and Cerebral Arteries: Role of Endothelium
Authors: Zurcher Shelley D. , Ong-Veloso Gleen L. , Akopov Sergey E. , Pearce William J.
Published: April 2003

In light of evidence that hypoxia inhibits cerebrovascular calcium influx and that the contractile importance of calcium influx is greater in neonatal than adult cerebral arteries, the present studies evaluate the hypothesis that the mechanisms involved in hypoxic cerebral vasodilation are different in newborn and adult cerebral arteries. Intact segments of ovine common carotid (COM) and middle cerebral (MCA) arteries from 3- to 7-day-old newborn lambs and nonpregnant adults were mounted in tissue baths, contracted with 1 µM 5-HT, and exposed to hypoxia for 20 min (PO2 ≈ 12 Torr). In endothelium-intact arteries, the magnitude of relaxation was similar and near maximal in all groups (range 82–92%) and did not vary with either age or artery type. However, the magnitude of hypoxic relaxation after endothelium removal was attenuated more in adult (COM 37 ± 6%, MCA 53 ± 7%) than in newborn (COM 75 ± 5%, MCA 93 ± 1%) arteries. In addition, endothelium-dependent responses to A23187, which like hypoxia increases endothelial cell concentrations of calcium, were attenuated in immature compared to mature arteries. Reductions of extracellular calcium concentration from 1.6 to 0.8 mM eliminated all age-dependent differences in relaxation responses to hypoxia. Together these data demonstrate that in newborn arteries, the endothelium-dependent component of hypoxic vasodilation is minimal, especially in intracerebral arteries, and robust relaxant responses to hypoxia depend on the high sensitivity of immature smooth muscle cells to decreases in PO2. In contrast, in adult arteries the smooth muscle sensitivity to decreases in PO2 is minimal and the endothelial component of hypoxic relaxation is particularly important in responses to hypoxia.
Effect of Two Types of Fish Oil Supplementation on Plasma and Erythrocyte Phospholipids in Formula-Fed Term Infants
Authors: Maurage Chantal , Guesnet Philippe , Pinault Michèle , Rochettede Lempdes Jean-Blaise , Durand Georges , Antoine Jean-Michel , Couet Charles
Published: April 2003

We studied the effect of docosahexaenoic acid (DHA) supplementation of infant formulas on fatty acid composition of blood phospholipids in term infants. Two fish oil supplemented formulas containing 0.45 wt% DHA and high (0.35%) or low (0.10%) eicosapentaenoic acid (EPA) were fed for 42 days and compared with a standard formula and breast milk. Infants fed supplemented formulas and breast milk had similar time-dependent changes for DHA from birth to day 42, i.e., slight decreases in plasma phospholipids and erythrocyte phosphatidylcholine and no change in erythrocyte phosphatidylethanolamine. Low-EPA formula prevented EPA accumulation but did not limit the significant decrease in arachidonic acid (AA) noted in infants fed high-EPA formula. These results suggest that term infant formulas should be supplemented with DHA-rich EPA, low fish oil and AA to achieve a fatty acid status in formula-fed infants similar to that of breast-fed infants.
Measurement of Cerebral Oxyhaemoglobin Saturation and Jugular Blood Flow in Term Healthy Newborn Infants by Near-Infrared Spectroscopy and Jugular Venous Occlusion
Authors: Buchvald Frederik F. , Kesje Klaus , Greisen Gorm
Published: April 2003

Data of cerebral haemodynamics and oxygenation are important for optimal treatment and prognosis in neonatal intensive care. Mostly premature and asphyxiated infants have been examined, but near-infrared spectroscopy (NIRS) allows estimations in healthy term newborns. In this study, cerebral venous saturation (CVsO2) and jugular blood flow (JBF) was estimated in 11 healthy term newborns. Mean CVsO2 was 64.12 ± 4.6%, which conform with expectations. Mean JBF was only 6.1 ml/100 g/min, which is unacceptably low compared to earlier published data. We discuss physiological and methodological aspects and conclude that the combination of NIRS and venous occlusion appears to be a reliable method for estimation of CVsO2 in normally healthy newborns, whereas the reason for the failure of the method for estimation of JBF is unclear.
Effect of Deferoxamine on Post-Hypoxic-Ischemic Reperfusion Injury of the Newborn Lamb Heart
Authors: Shadid Majidah , van Bel Frank , Steendijk Paul , Dorrepaal Caroline A. , Moison Ralph , van der Velde Enno T. , Baan Jan
Published: April 2003

Post-hypoxic-ischemic (HI) reperfusion induces excess production of non-protein-bound iron (NPBI), leading to formation of the highly reactive hydroxyl radical. We investigated whether the iron-chelator deferoxamine (DFO) could reduce reperfusion injury and improve left ventricular (LV) function. We produced severe HI in 14 newborn lambs and measured pre-HI, upon reperfusion, 60 and 120 min after HI the following parameters: mean aortic blood pressure, total peripheral resistance, stroke volume (SV), ejection fraction (EF) and LV contractility (pre-HI, 60 and 120 min post-HI). These parameters were assessed by measuring LV pressure (tip manometer) and volume (conductance catheter), using inflow occlusion to obtain slope (Ees) and volume intercept of the end-systolic P-V relationship (V10). We determined the antioxidative capacity, i.e. the ratio of ascorbic acid and dehydroascorbic acid (AA/DHAA) and malondialdehyde from coronary sinus blood at pre-HI and at 15, 60 and 120 min post-HI. Seven lambs received DFO (10 mg/kg i.v.) immediately after HI, 6 control lambs received a placebo. While neither Ees nor EF changed significantly in either group, the volume intercept V10 in the DFO-treated group was significantly smaller (0.25 ± 0.03 vs. 0.70 ± 0.09, p < 0.05), whereas SV was larger (3.6 ± 0.6 vs. 2.2 ± 0.2 ml, p < 0.05) and the AA/DHAA ratio was significantly lower at 15 min post-HI (p < 0.05) providing evidence for HI damage and for the protective effect of DFO. In conclusion: post-HI treatment of the newborn lamb with DFO has a modifying effect on free radical-induced damage to the myocardium and protects myocardial performance.
Longitudinal Multicentric Study of Plasma and Red Blood Cell Fatty Acids and Lipids in Preterm Newborns Fed Human Milk
Authors: Babin F. , Sarda P. , Bouglé D. , Billeaud C. , Mazette S. , Combe N. , Nouvelot A. , Descomps B. , Entressangles B. , Crastes de Paulet A. , Mendy F.
Published: April 2003

The present multicentric study (three centers) deals with the values of plasma and red blood cell fatty acids obtained in a group of 18 preterm newborns after 2 days (D2), 15 days (D15) and 5 weeks (37th week postconception: 37th wk) of human milk feeding. Analytical methods were randomized between the three centers and quality control was evaluated by repeated analysis of reference samples. 20:4 n–6 varied from 10.71 ± 1.58% to 9.51 ± 1.65 and 10.10 ± 1.42% in plasma phospholipids and from 16.59 ± 3.30% to 14.68 ± 3.14 and 18.24 ± 4.09% in red blood cell phosphatidylethanolamine (RBC-PE) at D2, D15 and 37th wk, respectively, contrasting with the important rise of the precursor (18:2 n–6) in all the fractions studied. In RBC-PE, 22:6 n–3 significantly declined from 3.52 ± 1.03% at D2 to 2.56 ± 0.83% at D15 (p < 0.02) and recovered its initial level at 37th wk (4.08 ± 1.94%). The recovery of long chain polyunsaturated fatty acid homeostasis at that time was also confirmed by the decline of 16:1 n–7 in cholesterol esters (10.69 ± 3.92 to 4.32 ± 2.38%).
Gender Difference in Cord Serum Ferritin Concentrations
Authors: Tamura T. , Hou J. , Goldenberg R.L. , Johnston K.E. , Cliver S.P.
Published: April 2003

We measured cord serum ferritin concentrations in a total of 255 infants (116 females and 139 males), and evaluated the association between these values and various neonatal as well as maternal characteristics. The mean ferritin concentration in females (166 ± 110 μg/l) was significantly higher than that in male infants (123 ± 77 μg/l). The gender differences in ferritin were significant within groups of infants with fetal growth restriction, those who weighed <3,000 g, those whose mothers were African Americans or <25 years old. Maternal serum ferritin concentrations at 36 weeks of gestation significantly correlated with cord serum ferritin of male infants (r = 0.32, p < 0.001), whereas the association was not significant for females (r = 0.09, p > 0.41). Although the mechanism of the gender difference is unknown, it may be important to consider the sex of neonates when evaluating their iron nutriture immediately after birth.
Oxidative Damage in Fetal Rat Brain Induced by Ischemia and Subsequent Reperfusion
Authors: Wakatsuki Akihiko , Izumiya Chiaki , Okatani Yuji , Sagara Yusuke
Published: April 2003

To determine whether ischemia followed by subsequent reperfusion can induce fetal cerebral oxidative damage, we created a model of fetal ischemia/reperfusion using rats at day 19 of pregnancy. Fetal ischemia was induced by unilateral occlusion of the utero-ovarian artery for 20 min. Reperfusion was achieved by releasing the occlusion and restoring the circulation for 30 min. The opposite uterine horn was used as control. We measured brain mitochondrial respiratory control index (RCI) and the concentration of thiobarbituric acid-reactive substances (TBARS) in each group. Arachidonic acid (AA) peroxidation induced by the incubation of brain microvessel fraction and AA was measured. AA peroxidation was also evaluated with and without aspirin, an inhibitor of cyclooxygenase and phenidone, which inhibits both of cyclooxygenase and lipoxygenase. The RCI significantly decreased by the occlusion with (p < 0.01) or without reperfusion (p < 0.05). The TBARS level significantly increased with occlusion plus reperfusion (p < 0.01). AA peroxidation was significantly greater in the occlusion and occlusion plus reperfusion groups than in the control groups (p < 0.01). Aspirin did not affect peroxidation, while phenidone significantly inhibited it in a concentration-dependent manner (p < 0.001). Accordingly, ischemia followed by reperfusion is likely to induce fetal cerebral lipid peroxidation, which may inhibit mitochondrial respiratory activity. The phenidone-inhibited enzyme lipoxygenase may participate importantly in this peroxidation.
Neonatal and Adult Rabbit Renal Brush Border Membrane Vesicle Solute Reflection Coefficients
Authors: Quigley Raymond , Flynn Marisa , Baum Michel
Published: April 2003

The interaction between solute and water in epithelial transport is represented by the solute reflection coefficient. Because the osmotic water transport process changes in the rabbit proximal tubule during maturation, there is a potential for the solute reflection coefficients to also undergo maturational changes. In the present study, we directly examined solute reflection coefficients in neonatal and adult brush border membrane vesicles (BBMV) using the stop-flow light-scattering technique. Reflection coefficients for NaCl, KCl, NaHCO3 and urea were found to be identical in the neonatal and adult BBMV and were not different from 1. Thus, although the water transport pathway undergoes changes in the proximal tubule during maturation, there is no evidence for changes in solute and water interaction. Because the reflection coefficients are not different from 1, there is no evidence for solvent drag in the proximal tubule apical membrane in either the neonatal or adult tubule.
Activities of Some Glycosaminoglycan- Degrading Enzymes in Wharton’s Jelly and Their Alteration in EPH-Gestosis (Pre-Eclampsia)
Authors: Romanowicz Lech , Bańkowski Edward , Sobolewski Krzysztof , Jaworski Stefan
Published: April 2003

Oedema, proteinuria, hypertension (EPH)-gestosis (pre-eclampsia) is associated with a premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs), both in the umbilical cord arteries and in Wharton’s jelly. It may be concluded from our previous report that such a phenomenon may be the result of reduction in degradation of these compounds. In order to support such a conclusion the activities of GAG-degrading enzymes in normal umbilical cord arteries and those taken from newborns delivered by mothers with EPH-gestosis were compared. It was found that EPH-gestosis results in a significant reduction in the activities of neutral endoglycosidases degrading most of the sulphated GAGs (except keratan sulphate). In the case of acidic endoglycosidases, no characteristic alterations have been found. Only the activity of heparan sulphate-degrading endoglycosidase significantly decreased. In contrast to the above-mentioned endoglycosidases, the activities of arylsulphatase B and 6-sulphatase distinctly increased. The decrease in the activities of endoglycosidases are thought to be responsible for EPH-gestosis-associated accumulation of sulphated GAGs in extracellular matrix of Wharton’s jelly. This leads to the suspicion that EPH-gestosis-induced changes in the GAGs composition may alter the fibrillogenesis conditions in Wharton’s jelly. The sulphated GAGs accumulated in Wharton’s jelly may interact with some growth factors which modify the myofibroblasts’ proliferation, gene expression, protein biosynthesis and other processes. A significance of EPH-gestosis-induced alteration in Wharton’s jelly is discussed.
Interleukin-6 Receptor Is Highly Expressed in the Ganglionic Eminence of the Human Fetal Brain
Authors: Ulfig Norbert , Friese Klaus
Published: April 2003

The expression of interleukin-6 receptor (IL-6R) has been investigated immunohistochemically in seven fetal brains with special reference to the ganglionic eminence (GE), a part of the telencephalic proliferative zone. Between the 22nd and 28th gestational week the GE stands out conspicuously due to its very high amount of intensely IL-6R-immunostained cells. Adjacent brain areas exhibit only very weak immunoreactivity. Between the 32nd and 36th week a moderate IL-6R immunolabelling is seen in the remnants of the GE. IL-6 may activate the immature IL-6R-positive cells to secrete a protease which is likely to be involved in GE involution and, perhaps, in the development of hemorrhage frequently occurring in the GE of premature infants.
The Effects of Dimethyl Sulfoxide on Renal Function of the Newborn Rabbit
Authors: Rijtema Mariette , Mosig Dolores , Drukker Alfred , Guignard Jean-Pierre
Published: April 2003

The purpose of this study was to establish the effects of intravenous dimethyl sulfoxide (DMSO), a solvent used in a wide variety of products (medicines), on kidney function in the newborn rabbit. Three groups of anesthetized, ventilated, normoxemic 4- to 8-day-old New Zealand White rabbits received a 90-min intravenous infusion of DMSO at a dose of 1.11 (group 1), 16.5 (group 2) or 111 μg/ kg/h (group 3). The only change observed in the animals of group 1 was a significant increase in filtration fraction (FF; p < 0.001), whereas no change at all was observed in the renal functional parameters of the animals of group 2. The highest dose of DMSO (group 3), however, caused a very significant (p < 0.001) decrease in renal blood flow (RBF) and a rise in renal vascular resistance (RVR), FF and urine volume (UV). Glomerular filtration rate (GFR) and systemic parameters such as pH, mean arterial blood pressure and heart rate did not change. The rise in GFR, RVR, UV (group 3 vs. 2) and FF (groups 3 vs. 2 and 2 vs. 1) was dose-dependent. No significant dose-dependent decrease in RBF was found. To the best of our knowledge, there are no previous reports on the effect of DMSO on renal function in the solvent doses used in this study. We ascribe the reported effects to the ‘immaturity’ of the newborn rabbit kidney. Consequently, this agent should be used with great caution in developmental studies.
Effects of Inhaled Nitric Oxide and High-Frequency Ventilation in Rabbits with Meconium Aspiration
Authors: Huang Qi-Wei , Sun Bo , Gao Feng , Zhang Yu-Ming , Wu Yue , Zhu Lie Wei , Lindwall Robert
Published: April 2003

Aim: To evaluate effects of inhaled nitric oxide (iNO) in experimental meconium aspiration treated with high-frequency (HFV) or conventional mechanical ventilation (CMV). Ventilated adult rabbits had meconium instilled intratracheally resulting in respiratory failure as evidenced by more than 50% reduction of dynamic lung compliance (Cdyn) and increase in mean oxygenation index (OI) from 1 to 16. The animals were then allocated to 2 groups treated without (control) or with iNO at 20 ppm (NO). In each group the animals were initially ventilated with CMV or HFV mode for 3 h and then in a crossover fashion with HFV or CMV for another 3 h (CMV→HFV, HFV→CMV), respectively. In the first 3 h of treatment, the animals subjected to HFV-CMV in the control, and those with both HFV-CMV and CMV-HFV in the NO group had significantly reduced OI. In the subsequent 3 h, the animals in the control group with CMV-HFV did not improve in OI and those with HFV-CMV had deteriorated. In the NO group with both CMV-HFV and HFV-CMV moderate improvement of OI was observed. Platelet aggregation capability and counts were significantly decreased and bleeding time prolonged in animals receiving iNO treatment. These results suggest that both HFV alone and a combined treatment of iNO with either CMV or HFV are more effective in improving blood oxygenation than that of CMV in this animal model. The influence of iNO on platelet aggregation should be considered.
Delayed Separation of the Umbilical Cord and Partial Deficiency of Sialyl Lewis X Antigen
Authors: Kaplan S.S. , Carlos T. , Fireman P.
Published: April 2003

A 5-week-old male infant presented with failure of separation of the umbilical cord. He was evaluated for the presence of integrin and selectin ligand leukocyte adhesion molecules on his neutrophils and monocytes. Integrin molecules appeared to be normally expressed, but expression of sialyl Lewis X (sLex) was decreased. The expression of sLex gradually increased, and the umbilical cord separated at 10 weeks of age. Further study revealed decreased numbers of sLex-positive neutrophils with a lower mean fluorescence intensity on neutrophils from cord blood compared to neutrophils in adult peripheral blood. This study indicates that this patient had an uncommonly low level of sLex expression and infers that adequate expression may be required for the inflammatory reaction needed for umbilical cord separation.
The Role of Bradykinin in Neonatal Hemodynamic Effects of ACE Inhibition
Authors: Tóth-Heyn Péter , Thonney Viani Michèle , Guignard Jean-Pierre
Published: April 2003

Angiotensin-converting enzyme (ACE) inhibitors exert their effects by inhibiting angiotensin II (AII) production, but also by inhibiting bradykinin (BK) degradation. In order to clarify whether BK is involved in the systemic effects of ACE inhibition in the newborn period, we investigated the effect of perindoprilat (20 μg/kg i.v.) in newborn rabbits, with or without the blockade of BK β2-receptors (Hoe 140, 300 μg/kg s.c.). The bolus infusion of perindoprilat resulted in a marked fall in mean arterial blood pressure (MBP) and a slight decrease in heart rate. BK receptor blockade had no effect on the perindoprilat-induced hypotension but the negative chronotropic effect of ACE inhibition was partly prevented by pretreatment with Hoe 140. We therefore conclude that BK is not involved in neonatal blood pressure regulation but that the ACE inhibition-induced neonatal bradycardia is at least partly BK- mediated.
Carnitine Supplementation and Ketogenesis by Small-For-Date Neonates on Medium- and Long-Chain Fatty Acid Formulae
Authors: Labadaridis J. , Mavridou I. , Sarafidou G. , Alexiou N. , Costalos C. , Michelakakis H.
Published: April 2003

Carnitine is a key molecule in energy production from various substrates. Although it is generally believed that it plays no role in the metabolism of medium-chain triglycerides, quite a few data exist to the contrary. In the present study we investigated the effect of carnitine on ketogenesis in small-for-date neonates fed formulae of equal caloric value and fat content that was predominantly long-chain triglycerides or medium-chain triglycerides (46% of total fat). According to our results there was a statistically significant interaction between carnitine and the chain length of the administered fat with respect to ketone production. Increased ketogenesis was only shown by the neonates receiving medium-chain triglycerides and carnitine. Our results provide further evidence for the involvement of carnitine in medium-chain triglyceride metabolism.
Independent and Combined Effects of Prolonged Inhaled Nitric Oxide and Oxygen on Lung Inflammation in Newborn Piglets
Authors: Ekekezie Ikechukwu I. , Thibeault Donald W. , Zwick David L. , Rezaiekhaligh Mohammad H. , Mabry Sherry M. , Morgan Ruth E. , Norberg Michael , Truog William E.
Published: April 2003

Clinical use of nitric oxide (NO) is usually in conjunction with high oxygen concentrations, the effects of which may include lung neutrophil accumulation, apoptosis and upregulation of antioxidant enzyme activity. To define the effects of NO on neutrophils from young piglets and its relationship to lung neutrophil dynamics during hyperoxia we exposed thirty piglets to room air (RA), RA+NO (50 ppm NO), O2 (FiO2≥0.96) or O2+NO for 5 days. Ten additional animals breathed RA+NO or O2+NO, then recovered in RA for 3 days before sacrifice. Neutrophil CD18 and intracellular oxidant production were measured by flow cytometry. Lung apoptosis were assessed by TUNEL assay. Lung myeloperoxidase, SOD and catalase were measured biochemically. When compared to RA group, there was significant reduction in neutrophil CD18 and intracellular oxidant production in the RA+NO group, but lung MPO was unchanged. The O2 and O2+NO groups did not differ in CD18 expression or in intracellular oxidant production, but had significant increase in lung myeloperoxidase compared to the RA group. Apoptosis increased significantly only in the O2+NO group. The O2 group showed significantly increased lung SOD and catalase activity compared to the RA group, whereas the RA+NO and O2+NO groups did not. We conclude that inhaled NO at 50 ppm decreases neutrophil CD18 expression as well as intracellular oxidant production. However, this effect does not impact lung neutrophil accumulation during concurrent hyperoxia. The combination of NO and O2 exposure produces an increase in lung apoptosis. Finally, NO may prevent upregulation of SOD and catalase activity during hyperoxia, potentially increasing injury.
Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?
Authors: Anand K.J.S. , Scalzo Frank M.
Published: April 2003

Self-destructive behavior in current society promotes a search for psychobiological factors underlying this epidemic. Perinatal brain plasticity increases the vulnerability to early adverse experiences, thus leading to abnormal development and behavior. Although several epidemiological investigations have correlated perinatal and neonatal complications with abnormal adult behavior, our understanding of the underlying mechanisms remains rudimentary. Models of early experience, such as repetitive pain, sepsis, or maternal separation in rodents and other species have noted multiple alterations in the adult brain, correlated with specific behavioral phenotypes depending on the timing and nature of the insult. The mechanisms mediating such changes in the neonatal brain have remained largely unexplored. We propose that lack of N-methyl-D-aspartate (NMDA) receptor activity from maternal separation and sensory isolation leads to increased apoptosis in multiple areas of the immature brain. On the other hand, exposure to repetitive pain may cause excessive NMDA/excitatory amino acid activation resulting in excitotoxic damage to developing neurons. These changes promote two distinct behavioral phenotypes characterized by increased anxiety, altered pain sensitivity, stress disorders, hyperactivity/attention deficit disorder, leading to impaired social skills and patterns of self-destructive behavior. The clinical important of these mechanisms lies in the prevention of early insults, effective treatment of neonatal pain and stress, and perhaps the discovery of novel therapeutic approaches that limit neuronal excitotoxicity or apoptosis.
Effects of Combined Superoxide Dismutase and Catalase on Somatosensory Evoked Potentials and Neuropathologic Changes in Asphyxiated Newborn Lambs
Authors: Abdel-Rahman Aladdin M. , Spitz Mark , Chang Yuan , Rosenberg Adam A.
Published: April 2003

The lamb model of neonatal asphyxia has been used to describe changes in cerebral blood flow, oxygen metabolism and mitochondrial function following a standard asphyxial insult. In addition, abnormalities in cerebral hemodynamics and mitochondrial function after asphyxia have been associated with injury mediated by oxygen free radicals. The purpose of this investigation was to describe changes in brainstem auditory and somatosensory evoked potentials and pathologic changes after asphyxia in the newborn lamb. In addition, the hypothesis that treatment with the oxygen free radical scavenging enzymes superoxide dismutase and catalase would enhance postasphyxia recovery of evoked potentials and ameliorate pathologic injury was tested. Electrophysiologic and pathologic abnormalities after asphyxia were demonstrated, but treatment with oxygen radical scavengers had no effect on these abnormalities.
Prophylactic Treatment of Endotoxic Shock with Monophosphoryl Lipid A in Newborn Rats
Authors: Wy Cherry Ann , Goto Masakatsu , Young Rita I. , Myers Thomas F. , Muraskas Jonathan
Published: April 2003

Mortality due to gram-negative septic shock remains high despite advances in medical care. Induction of endotoxin tolerance might be a new treatment strategy to prevent septic shock in the newborn. The present study was performed to show that an injection in pregnant rats of monophosphoryl lipid A (MPL), a nontoxic derivative of lipopolysaccharide (LPS), induces tolerance to Salmonella enteritidis LPS and tumor necrosis factor alpha (TNF-α) in their offspring. MPL at a dose of 2 mg/kg was injected into pregnant rats on the 19th day of gestation. Their 0-day-old offspring later received an intraperitoneal injection of S. enteritidis LPS or TNF-α. Newborn rats of MPL-treated dams exhibited a higher survival rate, absence of lactacidemia and lower plasma TNF-α concentration in response to S. enteritidis LPS when compared to the newborn rats of saline-treated dams. Newborn rats of MPL-treated dams were more tolerant to TNF-α than those of saline-treated dams. MPL injection into pregnant rats did not increase plasma endotoxin concentration in the fetuses, suggesting no placental passage took place, but it did increase plasma TNF-α concentration. We concluded that an injection of MPL into pregnant rats induced tolerance to LPS in their offspring, which might be due to TNF-α-induced TNF-α tolerance.
Physiological Parameters Evaluation following Apnea in Healthy Premature Infants
Authors: Curzi-Dascalova Lilia , Bloch Juliette , Vecchierini Marie-Françoise , Bedu Antoine , Vignolo Patricia
Published: April 2003

To assess responses to central and obstructive apnea, we performed 10-hour polygraphic recordings in healthy 33–34 wGA infants. Each apnea period was paired with a control period. The presence of body movements (BM) and augmented breaths (AB), the EEG, heart rate (HR), respiratory rate, phase relationships between thoracic and abdominal respiratory movements, and changes in SaO2 were evaluated. No apnea caused awakening. Apnea were not usually followed by motor events (no significant differences with control periods), with the exception of most obstructive apnea longer than 10 s. The mean percentage of changes following apnea, normalized to baseline values, was significant for the EEG (frequency slightly increased, mainly after obstructive apnea), HR (deceleration), and respiratory rate (increased). However, the mean values masked heterogeneity across apnea in the direction of the change in each parameter. The only significant correlation was between changes in HR and SaO2. The increases in EEG frequency and respiratory rate seen in our study can be considered markers of CNS activation, but were small and inconsistent. The heart rate decelerations and SaO2 changes are not activation markers. Thus, mechanisms underlying restarting of breathing efforts following apnea remain unclear in premature babies. Our investigation establishes the importance of using control data to distinguish between spontaneous and apnea-related events.