bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial and Hepatic Free Carnitine Concentrations in Pups of Diabetic Female Rats
Authors: Akısu Mete , Kultursay Nilgun , Coker Isıl , Huseyınov Afig
Published: April 2003

Background/Aims: Adequate carnitine levels are required for normal fatty acid and energy metabolism in heart muscle. It is well known that streptozotocin-induced diabetic rats develop myocardial carnitine deficiency and that carnitine therapy may be beneficial to the diabetic heart. Infants of diabetic mothers (IDM) are known to be at risk for developing a hypertrophic type of cardiomyopathy. In the present investigation, we examined the free carnitine concentration from cardiac and hepatic tissue in pups of streptozotocin-induced diabetic female rats. We also assessed the effect of maternal L-carnitine supplementation on the free carnitine concentration in pups of diabetic rats. Method: Three groups, each consisting of 4 Wistar albino female rats, were studied, Group 1 (untreated diabetic; n = 4) and group 2 (L-carnitine-treated diabetic; n = 4) rats were given streptozotocin (60 mg/kg) by intraperitoneal injection; group 3 were controls. During pregnancy, L-carnitine was given at a dose of 150 mg/kg by intraperitoneal injection once a day for 14 days. Cesarean section was carried out, and 113 newborn rats (group 1 n = 36; group 2 n = 38; group 3 n = 39) were obtained from all the pregnant rats. Results: The free carnitine concentration in myocardial tissue was significantly decreased in the female diabetic rats (p < 0.001). However, the free carnitine concentration from hepatic tissue in diabetic female rats was similar to that in controls. In pups of group 1 diabetic rats, a significantly decreased free carnitine concentration was found in both myocardial and hepatic tissue compared to group 2 and controls. The free carnitine content from myocardial and hepatic tissue was significantly elevated in the maternal L-carnitine-supplemented group when compared to group 1 and control pups (p < 0.001 and p < 0.05, respectively). Conclusions: The present study has demonstrated that the free carnitine concentration from myocardial and hepatic tissue is significantly reduced in pups of streptozotocin-induced diabetic female rats. This study has also shown that administration of maternal L-carnitine improves the carnitine level in pups of diabetic rats. A decreased myocardial carnitine concentration may be partly responsible for the development of cardiomyopathy in IDM.
Zur Entstellung C.G. Jungs unter Post-Jungianern
Authors: Krapp Manfred
Published: April 2003

In seiner neuen Einteilung der Post-Jungianer geht Samuels von vier Schulen aus: der fundamentalistischen, klassischen, entwicklungspsychologischen und der psychoanalytischen. Die psychoanalytische Schule (oder jungianische Fusion mit Psychoanalyse) ist durch die Verunglimpfung Jungs, die Geringschätzung zentraler jungianischer Inhalte und den massenhaften Import psychoanalytischer Auffassungen geprägt. Auf diese Merkmale werden einige Arbeiten deutscher Jungianer untersucht, die sich kritisch mit Jungs Vorstellungen zur zwischenmenschlichen Beziehung, Übertragung und Individuation auseinandersetzen. Anhand von vergleichenden Textanalysen wird die Ableitung dieser Thesen untersucht. Die hermeneutische Voreingenommenheit der untersuchten Arbeiten zeigt sich besonders in Entstellungen der Originaltexte Jungs durch tendenziöses Zitieren, welche oft den Vorwand für den Import psychoanalytischer Auffassungen bilden. Auch der Versuch, in Foulkes’ Begriff der Gruppenmatrix ein positives Gegenstücks zur Individuation zu konzeptualisieren, offenbart Schwierigkeiten im Aufbau einer hermeneutischen Beziehung zu dieser Konzeption. Die Entstellung der Texte Jungs reflektiert auch eine Schattenseite Jungs, zugunsten seiner Theorien die wissenschaftliche Objektivität nicht immer genau einzuhalten, und die Schwierigkeiten seines sprachlichen Diskurses aufgrund dessen Heterogenität und Ambiguität.
Peripheral Cell Loss Related to Calcium Binding Protein Immunocytochemistry in the Dorsal Cochlear Nucleus in CBA/CaJ Mice during Aging
Authors: Idrizbegovic Esma , Viberg Agneta , Bogdanovic Nenad , Canlon Barbara
Published: April 2003

The influence of cochlear hair cell and spiral ganglia neuron loss on calcium binding protein immunoreactivity (calretinin, parvalbumin and calbindin) in the dorsal and posteroventral cochlear nuclei (DCN and PVCN) in CBA/CaJ (CBA) mice during aging (1–39 months) was determined. Since calcium binding proteins have buffering properties against calcium overload, they may have a protective role during aging. It is shown that the percentage of calretinin- and parvalbumin-immunopositive neurons in the DCN showed a statistically significant positive correlation with inner hair cell loss, outer hair cell loss, and spiral ganglion cell loss. A correlation was also found between aging and the auditory periphery, and calcium binding proteins in the DCN. These findings imply that the pathophysiological state of the auditory periphery may influence the neuronal homeostasis in the dorsal cochlear nucleus.
Activity-Dependent Plasticity in the Adult Auditory Brainstem
Authors: Illing Robert-Benjamin
Published: April 2003

Over the past few years we have studied the plasticity of the adult auditory brainstem in the rat following unilateral changes to the pattern of sensory activation, either by intracochlear electrical stimulation or by deafening. We discovered that modifications to afferent activity induced changes in the molecular composition and cellular morphology throughout the auditory brainstem, including its major centers: the cochlear nucleus complex, the superior olivary complex, and the inferior colliculus. The time window studied ranged from 2 h to over 1 year following induction of changes to afferent activity. The molecular markers employed include the NMDA receptor subunit type 1, the cAMP response element binding protein (CREB), the immediate early gene products c-Fos, c-Jun and Egr-1, the growth and plasticity-associated protein GAP-43 and its mRNA, the calcium binding protein calbindin, the cell adhesion molecule integrin-α1, the microtubule-associated protein MAP-1b, and the neurofilament light chain (NF-L). As a consequence of the specific electrical stimulation of the auditory afferents or the loss of hearing, a cascade of events is triggered that apparently modifies the integrative action and computational abilities of the central auditory system. An attempt is made to relate the diverse phenomena observed to a common molecular signaling network that is suspected to bridge sensory experience to changes in the structure and function of the brain. Eventually, a thorough understanding of these events will be essential for the specific diagnosis of patients, optimal timing for implantation, and suitable parameters for running of a cochlear implant or an auditory brainstem implant in humans. In this report an overview of the results obtained in the past years in our lab is presented, flanked by an introduction into the history of plasticity research and a model proposed for intracellular signal cascades related to activity-dependent plasticity.
Imaging Plasticity in Cochlear Implant Patients
Authors: Giraud Anne Lise , Truy Eric , Frackowiak Richard
Published: April 2003

Auditory re-afferentation by cochlear implants (CI) offers a unique opportunity to study directly from within the auditory modality plastic changes taking place at organisational levels up to the supra- or polymodal level. These plastic changes resulting from deafness and chronic electrical stimulation can be studied using modern neuroimaging techniques. In this paper, we review the available techniques and the experimental approaches to human studies of plasticity, we discuss the different forms of plasticity that are associated with cochlear implantation and we point to the interest of imaging studies for providing a prognosis of functional outcome after implantation.
Prestin, the Motor Protein of Outer Hair Cells
Authors: Zheng Jing , Madison Laird D. , Oliver Dominik , Fakler Bernd , Dallos Peter
Published: April 2003

Prestin is a gene recently cloned from mammalian cochlear outer hair cells (OHC) using a single cell type, outer minus inner hair cell, specific suppressive subtractive hybridization procedure. The localization and gene expression profile of the prestin protein fits the pattern of OHC’s development of electromotility. When prestin is abundantly expressed in normally nonmotile kidney cells, nonlinear capacitance and motility that are normally only seen in OHCs can be recorded. Furthermore, both nonlinear capacitance and motility can be reduced by salicylate, a well-known inhibitor of electromotility. These data suggest that prestin is the motor protein of OHCs. Amino acid sequence and gene structure analysis indicate that prestin is the fifth member of a newly discovered anion transport family (SLC26) that includes PDS, DRA and DTDST, which are chloride-iodide transporters, Cl–/HCO–3 exchangers or sulfate transporters. Prestin shares overall structure similarity with this anion transporter family. Recently, intracellular anions (chloride or bicarbonate) were found to be essential for OHC electromotility and prestin’s function.
Vesicle Targeting in Hair Cells
Authors: Wenthold Robert J. , Safieddine Saaid , Ly C. Dune , Wang Ya-Xian , Lee Ho-Ki , Wang Chang-Yu , Kachar Bechara , Petralia Ronald S.
Published: April 2003

The mammalian hair cell has two distinct plasma membrane domains separated by tight junctions, the apical domain which contains the stereocilia and the basolateral domain which contains the presynaptic region. Little is known concerning the mechanisms that regulate vesicle trafficking to these two domains. Using SNAP 25 and syntaxin as baits, we carried out a yeast two-hybrid screen of the organ of Corti. We identified a novel syntaxin interacting protein, ocsyn, that is enriched in inner hair cells and concentrated at the apical pole. Our results are consistent with ocsyn playing a role in vesicle trafficking to the apical membrane of the hair cell.
Synthetic Surfactant Protein Analogues
Authors: Johansson Jan , Gustafsson Magnus , Palmblad Marie , Zaltash Shahparak , Robertson Bengt , Curstedt Tore
Published: April 2003

Surfactant preparations for the treatment of respiratory distress syndrome (RDS) that contain phospholipids and small amounts of the two hydrophobic proteins, SP-B and SP-C, are presently obtained from animal lungs. Since structural information about SP-B and SP-C is available, it appears possible to design analogues that can replace the native proteins in synthetic surfactants. SP-C contains a single helix, but analogues with the poly-Val sequence of the native molecule do not fold into a native-like α-helical conformation. However, replacement of all Val with Leu yields efficient folding into a helical structure and Leu-based SP-C analogues effectively accelerate spreading of surfactant lipids and exhibit some physiological activity in animal models of RDS. The inferior in vivo activity of synthetic surfactants containing SP-C only compared to that of surfactant preparations derived from natural sources may be caused by a lack of covalently linked palmitoyl groups in the analogues and/or absence of SP-B. SP-B is significantly larger than SP-C and has a tertiary fold of several amphipathic helices in a dimeric structure. A single simplified amphipathic helical peptide containing only Leu and Lys does not mimic the surface properties of SP-B in vitro. These circumstances make the design of SP-B analogues from solely structural considerations less likely to be successful than in the case of SP-C.
Cytokines, Pulmonary Surfactant and Consequences of Intrauterine Infection
Authors: Hallman Mikko
Published: April 2003

Excess of inflammatory cytokines is implicated in the sequence of inflammatory diseases during the perinatal period. Specific cytokines induce spontaneous premature labor and accelerate fetal lung maturity in case of chorioamnionitis. In addition, they are involved in the pathogenesis of chronic lung disease, periventricular white matter damage, shock and multiorgan damage. Deficient cytokine response of the immature lung is associated with severe respiratory distress syndrome and persistent fetal circulation syndrome. Surfactant supplementation remains the cornerstone among therapies in the premature infant. Brief courses of glucocorticoids, antioxidants or inhaled nitric oxides remain to be fully evaluated as possible adjunct therapies shortly after birth in small premature infants with severe cardiorespiratory failure.
Clinical Trials of Postnatal Corticosteroids: Inhaled and Systemic
Authors: Halliday Henry L.
Published: April 2003

Chronic lung disease (CLD) remains a common problem in neonatal intensive care units. Corticosteroids are being used increasingly to prevent or treat CLD. Uncertainties remain including the timing, duration and route of administration, and ratio of benefits to costs. This paper reviews the outcome of 39 randomized clinical trials of postnatal corticosteroid treatment. Twenty-five trials studied systemic steroids at three different postnatal ages; early (<96 h), moderately early (7–14 days), and delayed (>3 weeks). Fourteen-trials studied inhaled steroids (early: <7 days; late: >14 days) and inhaled versus systemic steroids. Systemic steroids have short-term beneficial effects improving gas exchange and lung mechanics to facilitate earlier extubation when used at any postnatal age in infants who are ventilator dependent. Early and moderately early steroids also reduce the risk of CLD at both 28 days and 36 weeks. For moderately early steroid use, there is also a reduction in neonatal mortality with 1 extra survivor for approximately every 16 babies treated (95% confidence interval 9–55). Proven adverse effects are either gastro-intestinal (bleeding) or metabolic (hyperglycaemia and hypertension). Unproven but potential adverse effects include decreased brain and lung growth. Inhaled steroids have been studied less thoroughly. Some studies report improvement in gas exchange and lung mechanics, but long-term benefits are not apparent to date in the published material. Trials comparing inhaled and systemic steroids suggest a more rapid response with the latter, but no significant differences in the rate of CLD at either 28 days or 36 weeks were found. Further research is necessary to define the roles of systemic and inhaled steroids in the prevention and treatment of CLD and to allow comparison of benefits to costs.
Plasma Cortisol, Cortisone and Urinary Glucocorticoid Metabolites in Preterm Infants
Authors: Midgley P.C. , Holownia P. , Smith J. , Moore M. , Russell K. , Oates N. , Shaw J.C.L. , Honour J.W.
Published: April 2003

Objective and Methods: In the fetal circulation, there is a low cortisol:cortisone (F:E) ratio (∼0.3) suggesting high activity of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2). The circulating F:E ratio rises after birth in term infants, but little is known about infants born prematurely. Our hypothesis was that the low fetal plasma F:E ratio would persist in infants born prematurely, due to persistently high tissue 11βHSD2 activity. To test this hypothesis, a longitudinal observational study of plasma F, E levels and urinary F and E metabolites was performed in 22 preterm infants of 24–31 weeks gestation. Results: Median plasma F was 234–380 nmol l–1, median 124–177 nmol l–1 from 1 to 14 days age. Plasma F fell with increasing postnatal and postconceptional age. The F:E ratio was 3 in the first week of life, and thereafter was 1–2, falling with postnatal age. Urinary glucocorticoid metabolites were low in quantity (∼48–120 µg kg–1 day–1), consisted of E metabolites until term, and did not reflect the plasma F:E ratio. Conclusions: The fetal plasma F:E ratio did not persist in these preterm infants, due to tenfold higher levels of F. The F:E ratios were similar to those reported in term infants. These data suggest that the low F:E ratio in utero is due to low fetal production of cortisol, and effective placental inactivation of maternal F by 11βHSD2.
Lewis and Secretor Gene Effects on Lewis Antigen and Postnatal Development of Lewis Blood Type
Authors: Ameno Setsuko , Kimura Hiroko , Ameno Kiyoshi , Zhang Xia , Kinoshita Hiroshi , Kubota Takako , Ijiri Iwao
Published: April 2003

Lewis (Le) and Secretor (Se) gene effects on postnatal change in Lewis antigens are described based on the quantitative analysis of Lewis antigens in blood. Genuine Lewis blood types were determined by Le and Se genotyping in DNA samples obtained from umbilical cord blood and infant blood. Lewisa (Lea) and Lewisb (Leb) antigen levels were measured by a time-resolved fluoroimmunoassay. We found that Lewis phenotypes in infants over 9 months of age agreed with the genuine types. In cord blood, the dosage effect of the Se gene on antigen levels was observed, but the Le gene effect was not observed. Both Se and Le gene effects were observed in newborn babies’ blood 3–6 days after birth.
A Brief Survey of the Modifications in Sensory-Secretory Organs of the Neonatal Rat Tongue
Authors: Sbarbati A. , Crescimanno C. , Merigo F. , Benati D. , Bernardi P. , Bertini M. , Osculati F.
Published: April 2003

Recent data obtained on rats suggest that in the days immediately following birth several events take place in the circumvallate papillae of the oral cavity. A phylogenetically primitive system of solitary chemosensory cells develops and is rapidly replaced by taste buds. The lipase-secreting von Ebner gland, which is associated with taste organs, begins to develop by forming short tubules. The intrinsic nervous system of the gustatory organs rapidly completes its maturation showing fast proliferation of fibers and immunocytochemical maturation. Intraepithelial lipid accumulation is visible in the non-receptorial mucosa of the tongue, showing aspects which suggest an active lipid secretion. These data demonstrate that in the rat the structure of the sensory-secretory organs of the newborn’s tongue shows a typical conformation with respect to the adult and rapidly changes its organization in the first week after the birth. At the present level of knowledge, it is difficult to link the anatomical structures to peculiar functional roles but the rather simple organization of the neonatal gustatory epithelium could be in relation to the dietary regimen. The data obtained in laboratory animals underline the necessity of studies on human newborns to update the anatomical knowledge of the oral chemoceptive system.
Effect of NG-Nitro-L-Arginine Methyl Ester on Intestinal Permeability following Intestinal Ischemia-Reperfusion Injury in a Rat Model
Authors: Luo Chih-Cheng , Chen Han-Ming , Chiu Cheng-Hsun , Lin Jer-Nan , Chen Jeng-Chang
Published: April 2003

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200–300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early NG-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI.
Relation between Birth Weight and Placenta Weight
Authors: Sanin Luz Helena , López Sandra Reza , Olivares Edith Tufiño , Terrazas Martha Corral , Silva Miguel Angel Robles , Carrillo Margarita Levario
Published: April 2003

With the goal to establish a model that relates birth weight to placenta weight, adjusted for the most documented predictors of birth weight, 300 live newborns were studied, all were products of single gestation. Inclusion criteria were newborns with gestational age of 37 weeks or older according to the date of last menstruation, whose mothers did not have diabetes mellitus, high blood pressure, pre-eclampsia, or eclampsia. The weight of the newborn was identified from the anthropometry data collected by previously trained nursing personnel in each of the participating hospitals. Immediately after delivery, the placenta was weighed. Multiple linear regression was used to see the effect of placenta weight and each variable on birth weight. The mean of birth weight was 3,369 g with a standard deviation (SD) of 445 g. Placenta weight had a mean of 537 g (SD: 96 g). The relation between the weight of the placenta and the birth weight was significant, and we found that for each gram increase in placenta weight, birth weight is increased by 1.98 g (SE = 0.25, p < 0.01) and this relation is not linear, since the quadratic term is significant. Placenta weight has a nonlinear relation to the birth weight and is an important predictor of birth weight. Together with the gestational age and the maternal age and size, it explains 32% of the variability of birth weight. Placenta weight can be a ‘sentinel’ indicator of nutritional and/or environmental problems.
Prenatal Ethanol Consumption Increases Retinol and Cellular Retinol-Binding Protein Expression in the Rat Fetal Snout
Authors: Zachman Richard D. , Grummer Mary A.
Published: April 2003

Fetal exposure to ethanol disrupts normal craniofacial development, resulting in characteristic features of fetal alcohol syndrome (FAS). One mechanism that could result in some anomalies of this syndrome is through ethanol disrupting the regulatory role played by vitamin A in fetal development, thereby inducing morphological alterations which manifest as FAS. This work begins to explore a possible interaction of ethanol with vitamin A in craniofacial development. Retinoid levels and the expression of cellular retinol-binding protein (CRBP) and retinoic acid receptor (RAR) mRNA were determined in snouts of 20-day fetuses exposed to ethanol throughout gestation, compared to controls. Snout retinol and retinyl palmitate levels were elevated in fetuses of ethanol-treated rats, but retinoic acid levels were unaffected. The expression of CRBP mRNA, as determined by Northern analysis, was greater in snouts of fetuses exposed to ethanol, but there was no change in RAR α, β, γ or retinoid X receptor β mRNA. These results demonstrate that prenatal ethanol consumption can alter certain markers of vitamin A metabolism and function in the fetal snout.
Auditory Brainstem Response and Unbound Bilirubin in Jaundiced (jj) Gunn Rat Pups
Authors: Ahlfors Charles E. , Shapiro Steven M.
Published: April 2003

The role of plasma bilirubin-albumin binding in the pathogenesis of kernicterus in human newborns is controversial. Kernicterus in the jaundiced (jj) Gunn rat pup, an animal model for kernicterus, prolongs interwave intervals and decreases wave amplitude in the auditory brainstem response (ABR). Plasma total bilirubin concentration (TBC), albumin concentration, and unbound bilirubin concentration (UBC), a measure of bilirubin-albumin binding, were measured in 16-day-old jj Gunn rat pups (n = 21) and compared with ABR wave latencies, interwave intervals, and wave amplitudes by linear correlation. The UBC, but not the TBC or TBC/albumin ratio, correlated positively and significantly with ABR I–II and I–III interwave intervals (r = 0.55, p = 0.009, and r = 0.60, p = 0.004, respectively). The UBC, but not the TBC or TBC/albumin ratio, predicts bilirubin toxicity, as measured by bilirubin-induced ABR changes in jj Gunn rat pups.
Effect of Tilting on Cerebral Hemodynamics in Preterm and Term Infants
Authors: Pichler Gerhard , van Boetzelar Marjolijn C. , Müller Wilhelm , Urlesberger Berndt
Published: April 2003

Tilting is known to cause changes in hemodynamics due to hydrostatic pressure. The present study is an analysis of changes in cerebral hemodynamics measured by near infrared spectroscopy (NIRS) following tilting up and down in preterm and term infants. A significantly different effect of tilting up in comparison to tilting down on total hemoglobin in preterm infants and on the ‘hemoglobin oxygenation index’ in preterm and term infants was observed. In preterm infants, tilting up and down had a significantly different effect on cerebral blood volume (CBV), with an increase after tilting down and a decrease after tilting up. In term infants, tilting had no significant effect on CBV comparing these two procedures. We think that NIRS provides a good method to measure cerebral hemodynamics following tilting, whereby different reactions in infants of different postconceptional age can be observed.
The Effects of Bedside Blood Gas Monitoring on Blood Loss and Ventilator Management
Authors: Moya Martin P. , Clark Reese H. , Nicks Joanne , Tanaka David T.
Published: April 2003

Introduction: We examined whether the bedside SensiCath® Blood Gas Monitoring System could reduce both blood loss and the time needed to make ventilator-setting changes in a population of very low birth weight (VLBW; <1,500 g) infants. Material and Methods: A prospective, group sample trial was conducted on ventilator-dependent newly born VLBW infants. The trial was unblinded due to the nature of the device and parental consent was obtained before study enrollment. A total of 44 patients were studied. Results: There was no difference (mean ± SD) between the SensiCath group and controls with respect to birth weight, gestational age, pH, PCO2, PO2 or Apgar at 5 min (median 6, both groups). The amount of blood loss for arterial blood gas (ABG) measurement alone was less in the SensiCath group compared to the control group (1.2 ± 0 ml vs. 6.7 ± 2.4 ml, p < 0.001) and the total blood loss was also less in the SensiCath group (8.1 ± 5 ml vs. 10.5 ± 6.3 ml, p < 0.001), but there was no significant difference between each group in the amount of blood transfused. The time to obtain ABG results and to make a ventilator change was shorter in the SensiCath group compared to control (2 ± 0 vs. 26 ± 21 min, p < 0.001). Discussion: Use of the modified SensiCath monitoring system permits near zero blood loss for ABG assessment and greatly reduces the time needed to make ventilator management decisions.
Perfluorochemical Liquids Do Not Stimulate Endothelin-1 or Nitric Oxide Production in Human Blood Leukocytes
Authors: Nakstad Britt , Wolfson Marla R. , Aspelin Trude , Lindemann Rolf , Shaffer Thomas H. , Fugelseth Drude , Lyberg Torstein
Published: April 2003

The purpose of these studies was to examine if perfluorochemical (PFC) liquids stimulate blood leukocytes to secrete nitric oxide (NO) and/or endothelin-1 (ET-1). As such, NO and ET-1 may modulate broncho- and vascular dilatation and constriction, respectively, and thereby influence the clinical condition of a patient in respiratory distress with persistent pulmonary hypertension. Blood leukocytes in their natural habitat (whole blood) were incubated in the presence of two different perfluorochemicals (perflubron and perfluorodecalin). The overall response in ET-1 or NO (indirectly measured as nitrite/nitrate) production was examined at increasing PFC percentages (wt/vol) of PFC/whole blood. The lowest proportion used, 0.001% (wt/vol), was relevant to serum concentrations of PFC observed in liquid-ventilated individuals, whereas the highest proportion PFC, 50% (wt/vol), would mimic a situation where leukocytes are presented to PFC-filled airways. Plasma levels of freshly drawn blood, similar to levels of incubated (6 h) non-PFC-supplemented cultures, were ET-1 0.59 ± 0.07 pg/ml (6 h, mean ± SEM) and NO–2/NO–3 50 ± 9 µM (6 h). Perflubron or perfluorodecalin did not induce significant differences in ET-1 or NO–2 /NO–3 levels as function of PFC type or dose. In conclusion, PFC liquids do not stimulate production in leukocytes in vitro of substances that may modulate constriction or dilatation in the vascular and respiratory tract systems.
Elevated Intact Parathyroid Hormone Is Associated with Reduced Biochemical Markers of Bone Formation and Resorption Measured in Blood in Infant Piglets Receiving Oral Dexamethasone for 15 Days
Authors: Guo Chun-Yuan , Weiler Hope , Atkinson Stephanie A.
Published: April 2003

Seven-day-old male Yorkshire piglets were randomized to receive either dexamethasone (DEX) 0.5 mg/kg/day or placebo (water) for 15 days (n = 8/group). Body weight and length, plasma intact parathyroid hormone (PTH), N-Mid osteocalcin and C-terminal telopeptide of type I collagen (CTx) were measured at baseline and end of the study. The indices of bone metabolism did not differ between DEX and placebo groups at baseline. At the end of the study, plasma intact PTH was increased (p < 0.01) and N-Mid osteocalcin (p < 0.01) and CTx (p < 0.01) were decreased from baseline value in the DEX group but not in the placebo group. The reduction (Z-score) in N-Mid osteocalcin was greater than that in CTx (p < 0.05). We conclude that exogenous DEX in young piglets stimulates a rise in circulating intact PTH. Both circulating CTx and osteocalcin are reduced with the decline in osteocalcin greater than that in CTx.
Bronchopulmonary Dysplasia and Surfactant
Authors: Bancalari Eduardo , del Moral Teresa
Published: April 2003

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in preterm infants who survive prolonged mechanical ventilation. Exogenous surfactant administration clearly reduces the severity of respiratory distress syndrome (RDS) and consequently the need for aggressive ventilation and prolonged oxygen therapy. However, the overall incidence of BPD has not decreased but in fact may even have increased after the introduction of surfactant therapy. There are several reasons for the lack of effect on the incidence of BPD. First, surfactant therapy and antenatal steroids have markedly increased survival of the smallest infants, i.e. those at higher risk of BPD. Second, there has been a change in the pathogenesis and the presentation of BPD. While the classic BPD was mainly the consequence of barotrauma and oxygen toxicity, the new BPD seen in the surfactant era results from the interaction of many factors that lead to prolonged mechanical ventilation and colonization of the airway with pathogens that may trigger an inflammatory cascade. While the overall incidence of BPD has not been substantially modified by surfactant therapy, the more severe cases of BPD have become less common. The data regarding the effect of surfactant administration on the incidence and severity of BPD is conflicting. There is substantial evidence that the administration of exogenous surfactant, either as prophylaxis or as a treatment in infants with established RDS, can reduce neonatal mortality and the occurrence of BPD or death. The data also suggest that prophylactic or early administration is more effective than late treatment in reducing mortality and BPD or death. No clear difference has been documented between natural or synthetic surfactant treatment in terms of their effect on incidence of BPD or mortality. The lack of consistency in the results with surfactant replacement may reflect the changing pathogenesis of BPD and the multiplicity of factors involved among which surfactant deficiency is only one.
Lung Epithelial Ion Transport in Neonatal Lung Disease
Authors: Pitkänen Olli
Published: April 2003

Lung epithelial ion transport promotes salt and water movement across the fetal and neonatal lung epithelium. The mechanism is dependent on basolateral membrane Na-K-ATPase and the apical membrane Cl– and Na+ channels. During fetal life active secretion of Cl– and parallel movement of Na+ across the epithelium into the developing lung lumen induce accumulation of liquid into the future airspaces. Postnatally, however, absorption of fluid from the airspaces must start. Present evidence suggests that activation of Na+ transport from the lumen into the basolateral direction drives fluid absorption and results in an essentially dry air-filled alveolus. In laboratory animals amiloride, a Na+ channel blocker, induces respiratory distress and impedes lung fluid clearance. One of the epithelial amiloride-sensitive Na+ channels, ENaC, is composed of three homologous subunits that differentially respond to glucocorticoid hormone. In newborn infants an increase in pulmonary fluid and a defective Na+ transport associate with respiratory distress. The ontogeny, subunit composition and function of ENaC along the respiratory tract are currently under investigation. It will be interesting to find out whether the subunit composition and function of lung ENaC respond to the therapy of the critically ill newborn infant.
Hormonal Factors in the Morbidities Associated with Extreme Prematurity and the Potential Benefits of Hormonal Supplement
Authors: Yeung Melinda Y. , Smyth John P.
Published: April 2003

Cortisol and thyroid hormones are known to modulate the maturation of various fetal organ systems, enzymes, and biochemical pathways. The cortisol furnished by the structural and biochemical immature fetal adrenal gland renders the extremely premature infants relatively cortisol deficient in comparison with the term newborns. The premature infants also have elevated fetal androgens, the production of which persists until ≈42 weeks of postconceptional age. The androgens produced by the fetal adrenal cortex and the müllerian inhibiting substance produced by the fetal testis have antiglucocorticoid and inhibitory effects on human fetal lung growth and maturation in vitro. Hypothalamic-pituitary-thyroid axis and thyroid function are also immature in extreme prematurity. In addition, there is reduced tissue thyroid hormone responsiveness. Superimposed on this is the reduced thyroid function seen in non-thyroidal illness in which elevated cytokine levels have been implicated. Repeated courses of antenatal steroids and high-dose postnatal dexamethasone appear to be deleterious to lung and brain development. This may be through inhibition of cell replication and catabolism as well as decreased thyroid-stimulating hormone secretion and reduced peripheral conversion of T4 to T3. Furthermore, dexamethasone has been found to enhance neurosteroid production in the immature brain, potentially altering brain development. Considered together, the relative cortisol deficiency/androgen excess and reduced thyroid function as well as prolonged high-dose postnatal dexamethasone therapy in these infants may be important factors in their high degree of morbidity. We propose to restrict antenatal steroids to a single course and hypothesize that the overall outcome of low-gestation infants would be improved with (1) hydrocortisone (i.v./p.o.) supplement at a fixed dose of 0.5 mg/kg birth weight every 12 h in infants <30 weeks of gestation from birth till 32 weeks of postconceptional age and (2) T3 (i.v./p.o.) supplement at a fixed dose of 0.4 µg/kg birth weight every 12 h in those <27 weeks of gestation from birth till 32 weeks of postconceptional age.
Basement Membrane Biomarkers in Very Low Birth Weight Premature Infants
Authors: Aghai Zubair H. , Arevalo Ronald , Lumicao Lorna , Lesser Martin , Shi Quihu , Jain Ajey , Krauss Alfred N. , Auld Peter A.M. , Hanauske-Abel Hartmut M.
Published: April 2003

Basement membranes, critical for vital organs like the lungs, consist of two interwoven homopolymers, one assembled by type IV collagens and one by laminins. We hypothesized their serum antigens C-IV and P1, respectively, to be global measures for the maturity of these organs. In 39 very low birth weight premature neonates (means: gestational age, 25.8 weeks; birth weight, 779 g) requiring intensive care, we analyzed these biomarkers during the first two months post partum. Median C-IV and P1 exceeded adult levels by one order of magnitude. The individuals with the lowest first week C-IV values (mean: 667 ng/ml) required significantly longer neonatal intensive care unit stays than those with the highest values (mean: 2,467 ng/ml), on average 109 vs. 80 days (p = 0.008) irrespective of gestational age. Patients diagnosed with bronchopulmonary dysplasia (BPD) at 36 weeks postconceptional age, already in their first week of life displayed C-IV levels lower than in controls, suggesting a defect in pulmonary basement membrane remodeling. This is the first identification by a matrix biomarker of a BPD-antecedent state.
Effects of Different Fluids on the Relationship between Swallowing and Breathing during Nutritive Sucking in Neonates
Authors: Mizuno Katsumi , Ueda Aki , Takeuchi Tosio
Published: April 2003

This study in 10 term infants investigated the effects of different fluids on the coordination between swallowing and breathing during bottle feedings. Sucking pressure, swallowing, breathing and O2 saturation were examined in each infant during bottle feedings with breast milk, formula and distilled water. When receiving breast milk, the infants showed a significantly higher breathing rate than with the other liquids. Swallows followed by inspiration were demonstrated less often with breast milk compared with formula or distilled water. In conclusion, expressed breast milk is suitable for neonates because better coordination between swallowing and breathing could be obtained and subclinical aspiration could be prevented.
Nitration of Bax and Bcl-2 Proteins during Hypoxia in Cerebral Cortex of Newborn Piglets and the Effect of Nitric Oxide Synthase Inhibition
Authors: Ashraf Qazi M. , Zubrow Alan B. , Mishra Om P. , Delivoria-Papadopoulos Maria
Published: April 2003

Previous studies have shown that cerebral tissue hypoxia results in increased expression of Bax protein, thereby altering the ratio of Bax to Bcl-2 or formation of Bax/Bcl-2 heterodimer. Hypoxia also induces the generation of nitric oxide free radicals in the cerebral cortex of newborn animals. The present study tests the hypothesis that tissue hypoxia will result in nitration of Bax and Bcl-2 proteins in the neuronal nuclei of newborn piglets. Studies were performed in 22 piglets, 3–5 days old, divided into normoxic (n = 7), hypoxic (n = 9) and hypoxic + NNLA (n = 6) groups. Hypoxia was induced by decreasing the FiO2 (5–7%) for 60 min and cerebral hypoxia documented by determining tissue ATP and phosphocreatine (PCr) levels. The density of protein bands was expressed as absorbance (OD × mm2). PCr levels were 3.03 ± 0.85 µmol/g brain in the normoxic group and 0.88 ± 0.32 µmol/g brain in the hypoxic group (p < 0.001 vs. normoxia) and 0.55 ± 0.13 (p < 0.001 vs. normoxia) in the NNLA-treated hypoxic group. There was increased nitration of Bax protein in hypoxic neuronal nuclei as compared to normoxic and NNLA-treated-hypoxic group nuclei: 211.61 ± 25.93 versus 124.8 ± 14.88 and 133.86 ± 7.42 OD × mm2, respectively (p < 0.001 vs. normoxia). Nitration of Bcl-2 was not altered significantly in either group. We conclude that there is increased nitric oxide-mediated nitration of Bax in cortical neuronal nuclei during hypoxia and that this increase correlates inversely with the decrease in tissue energy levels. We speculate that, during hypoxia, nitration of Bax and Bcl-2 proteins may regulate heterodimer formation and activation of programmed cell death mechanisms.
Minimal Effective Dose of Indomethacin for the Treatment of Patent Ductus arteriosus in Preterm Infants
Authors: Dumas de la Roque E. , Fayon M. , Babre F. , Demarquez J.L. , Pedespan L.
Published: April 2003

The aim of this study was to determine if it was possible to decrease the number of boluses of indomethacin for the treatment of patent ductus arteriosus. This retrospective study included 46 preterm neonates (<34 weeks’ GA) who had had an ultrasound diagnosis predictive of subsequent symptomatic patent ductus arteriosus. All patients had received a daily intravenous doses of indomethacin, 0.1 mg/kg. Mean age at initiation of treatment was 4.5 ± 3.1 days. Patency of the ductus arteriosus was controlled echocardiographically each day and treatment was discontinued as soon as the ductus arteriosus was closed. The initial success rate was 84.7%, of which 6.5% reopened. The mean cumulative dose of indomethacin was 0.35 mg/kg. There was no correlation between gestational age or birth weight and total cumulative dose. Overall tolerance was satisfactory with only one case of transient acute renal failure. A weak correlation between the cumulative dose of indomethacin and natremia (r = –0.43) or weight gain (r = 0.35) was noted, and none with serum creatinine or blood urea nitrogen levels. We confirm that lower indomethacin treatment of patent ductus arteriosus in premature neonates are as effective as standard protocols.
Tonotopic and Somatotopic Representation in the Nucleus basalis of the Barn Owl, Tyto alba
Authors: Wild J.M. , Kubke M.F. , Carr C.E.
Published: April 2003

We have investigated the somatosensory and auditory representations in the nucleus basalis of the barn owl. In pigeons and finches, the nucleus basalis contains a representation of the beak and an auditory area. In the barn owl, the nucleus basalis also contains a complete somatotopic map of the head and body (as in the budgerigar), with a tonotopically organized auditory area in close proximity to the representation of the facial ruff and the preaural area. Recordings within and around the nucleus basalis revealed predominantly (about 80%) contralateral responses to somatic stimulation. The somatotopic map was oriented with the head down and rostral. Penetrations revealed an over-representation of the feet in dorsal basalis, followed by the rest of the body and wings more ventrally. Towards more rostral positions in nucleus basalis, responses from the head and beak predominated ventrally. The auditory response area was encountered below the region that responded to stimulation of the facial ruff and preaural flap regions and above a region responsive to beak stimulation. Auditory responses were tonotopically organized, with low best frequencies dorsal. Some penetrations yielded predominantly monaural responses with a fairly broad dynamic range, similar to those recorded from the ventral nucleus of the lateral lemniscus (LLV) and the cochlear nucleus angularis, whereas other penetrations contained predominantly binaural responses sensitive to interaural time differences (ITD). The physiological responses could be predicted on the basis of auditory projections to the nucleus basalis. An injection of biotinylated dextran amine (BDA) in the auditory region of nucleus basalis retrogradely labeled cells in both the caudal and rostral parts of the intermediate lateral lemniscal nucleus (LLIc and LLIr), and a few cells in the anterior part of the dorsal lateral lemniscal nucleus (LLDa, previously known as nucleus ventralis lemnisci lateralis, pars anterior, or VLVa) and in the posterior part of the dorsal lateral lemniscal nucleus (LLDp, previously known as nucleus ventralis lemnisci lateralis, pars posterior, or VLVp). A large injection of cholera toxin B-chain (CTB) into the nucleus basalis also produced dense retrograde labeling of a previously unidentified nucleus on the lateral aspect of the rostral pons, that we here call nucleus pontis externus (PE). An injection of CTB into PE produced dense retrograde labeling of the contralateral dorsal column nuclei and anterograde labeling of the ipsilateral lateral and dorsolateral nucleus basalis. Together these results define major somatosensory and auditory projections to the owl telencephalon that bypass the thalamus.
Ethological Concepts Revisited: Immediate Early Gene Induction in Response to Sexual Stimuli in Birds
Authors: Ball G.F. , Balthazart J.
Published: April 2003

Courtship behaviors were interpreted by ethologists as being examples of ‘sign stimuli’ that would act as ‘releasers’ of stereotypic species-typical behaviors in conspecifics. A key component of the sign stimulus concept is that some form of stimulus filtering occurs that is responsible for the marked selective behavioral responsiveness. Studies of immediate early gene induction in the avian brain in response to conspecific stimuli associated with courtship and mating reveal that such gene induction is highly selective. In male Japanese quail (Coturnix japonica), studies of the immediate early gene c-fos or zenk have been conducted in birds engaging in both appetitive and consummatory aspects of male sexual behavior. High induction of immediate early genes occurs in hypothalamic and limbic areas such as the medial preoptic nucleus, bed nucleus striae terminalis and parts of the archistriatum in birds who had copulated and/or who had expressed a learned social proximity response, reflecting appetitive sexual behavior. Immediate early gene expression was also increased in telencephalic areas such as the hyperstriatum ventrale that presumably plays a role in the integration of sensory cues related to female recognition. In European starlings, studies of zenk induction have been conducted in females who hear male-typical courtship song. Clayton and Mello had shown that zenk is induced in the auditory telencephalon of canaries and zebra finches at high levels specifically in response to conspecific song. Immediate early genes such as fos and zenk are also expressed in song control nuclei specifically in association with song production. In starlings it was found that song was effective in rapidly inducing zenk expression in the auditory telencephalon in males and in females in the breeding as well as in the non-breeding season. Thus, the expression is not greater in females who use song to choose mates or during the breeding season when females are choosing mates. However, there is evidence that high levels of induction in certain areas of the auditory telencephalon in females are greater in response to songs organized in longer bouts that females prefer. Though immediate early gene induction in the brain does not exactly mimic selective behavioral responses to sign stimuli it may represent one important way in which stimulus selectivity of the sort hypothesized previously by Tinbergen and Lorenz is coded. Engaging in species-typical behaviors is also associated with motor-driven immediate early gene expression.
Firing Patterns and Morphological Features of Neurons in the Pigeon Nucleus rotundus
Authors: Hu Jing , Wang Shu-Rong
Published: April 2003

In birds, the thalamic nucleus rotundus relays visual information from the midbrain optic tectum to the forebrain ectostriatum. Using brain slices, the present study investigates the firing patterns and morphological features of 41 neurons in various divisions of the pigeon nucleus rotundus. The results indicate that these rotundal cells could be physiologically categorized into two types according to their firing patterns in response to depolarizing current pulses. Type I cells (76%) are characterized by a multi-phase firing pattern producing a single spike, late-spiking and fast-spiking as current intensity increases. Cells of type II (24%) are characterized by a rapid spiking-inactivation, discharging only one or two small spikes at the onset of current injections. However, intracellular staining shows no significant morphological differences between the two physiological types of cells in terms of somatic and dendritic field sizes, or an average density of dendritic varicosities, although each cell type includes both small- and large-sized dendritic fields. It is likely that the firing patterns and morphological features of rotundal neurons might not be correlated with each other or with rotundal divisions.