摘要:

Maturation of fetal ductus arteriosus is associated with increased constriction in response to maternally administered indomethacin. Recently retinoic acid has been shown to be important in development of the fetal ductus arteriosus. To determine whether retinoid might be of value in the treatment of patent ductus arteriosus in premature infants, we studied the response of fetal ductus arteriosus to indomethacin with and without pretreatment with vitamin A (1 mg (3000 IU)/kg, intramuscular injection) in near-term and preterm rats. Maturation of the ductus arteriosus was studied by measuring the inner diameters of the ductus arteriosus (D) and main pulmonary artery (P) to get D/P ratio 4 h after orogastric administration of 1 mg/kg indomethacin. D/P was 1.0 in the fetus before administration of indomethacin. In near-term fetuses on the 21st d without vitamin A, D/P decreased to 0.54 with indomethacin, whereas it decreased to 0.27 (p< 0.05) in those with pretreatment with vitamin A on the 19th and 20th d. In preterm fetuses on the 20th d without pretreatment with vitamin A, D/P decreased to 0.82 with indomethacin, whereas it decreased to 0.66 (p< 0.05) in those with pretreatment with vitamin A on the 19th d. It is concluded that maternally administered vitamin A accelerates maturation of the ductus arteriosus in fetal rats.Abbreviations: DA,ductus arteriosus;D/P,ductus arteriosus/main pulmonary inner diameter ratio;PDA,patent ductus arteriosus

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We hypothesized that nitric oxide (NO) production by the fetal ductus arteriosus is limited because of low fetal PO2, but that at neonatal PO2, NO might be an important regulator of ductus arteriosus tone. We exposed isolated rings of fetal lamb ductus arteriosus to elevated PO2. L-NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and methylene blue and 6-anilino-5,8-quinolinedione (LY83583), inhibitors of guanylate cyclase, produced constriction of the ductus arteriosus. When ductus arteriosus rings were exposed to low PO2, L-NAME had no effect, and methylene blue and LY83583 had only a small effect on ductus arteriosus tone. Sodium nitroprusside and calcium ionophore A23187 relaxed ductus arteriosus rings more than aortic rings, and relaxed ductus arteriosus rings from immature fetuses more than those from late gestation fetuses. In contrast, ductus arteriosus rings from both early and late gestation were equally sensitive to 8-bromo-cGMP. By both reverse transcriptase-polymerase chain reaction and immunohistochemistry, endothelial cell NOS and inducible calcium-independent NOS, but not nerve cell NOS, were detected in the ductus arteriosus. Inducible NOS was expressed only by endothelial cells lining the ductus arteriosus lumen; in contrast, endothelial cell NOS was expressed by both luminal and vasa vasorum endothelial cells. The role of inducible NOS in the ductus arteriosus is uncertain because the potency of a specific inducible NOS inhibitor in constricting the ductus arteriosus was negligible compared with that of an endothelial cell NOS inhibitor. We speculate that NO may be an important regulator of ductus arteriosus tone at high but not low PO2. The endothelial cell NOS isoform found in vasa vasorum may be an important source of NO because removal of ductus arteriosus luminal endothelium only partially blocks the effects of L-NAME, methylene blue, and LY83583.Abbreviations: NO,nitric oxide;NOS,nitric oxide synthase;ecNOS, ncNOS, iNOS,endothelial cell, nerve cell, and inducible calcium-independent isoforms of NOS;L-NAME,NG-nitro-L-arginine methyl ester;L-NIL,L-N6-(1-iminoethyl)lysine;L-NA,L-NG[-nitro-L-arginine];LY83583,6-anilino-5,8-quinolinedione;SNP,sodium nitroprusside;vWF,von Willebrand factor;8-Br-cGMP,8-Bromo-guanosine 3′,5′-cyclic monophosphate;RT,reverse transcriptase;PCR,polymerase chain reaction;SNAP,S-nitroso-N-acetylpenicillamine;ET-1,endothelin-1

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Coagulase-negative staphylococcal septicemia is the most prominent nosocomial infection in neonatal intensive care units. Immaturity of host defenses in premature neonates is assumed to constitute an important risk factor. Opsonophagocytosis is considered to be the key host defense system against staphylococci with IgG antibodies as a major opsonin. For this reason we have studied serum IgG antibody titers and opsonic activity to coagulase-negative staphylococci in 20 infants with septicemia and 40 matched control subjects. In addition, we assessed the effect of administration of fresh frozen plasma (FFP) on IgG antibody titer and serum opsonic activity in 12 patients with septicemia. IgG antibodies, quantified by ELISA and opsonic activity, determined by flow cytometry, were expressed as a percentage of the value of pooled normal human reference serum. Both patients and control subjects showed low IgG titers (median, 21%; range, 1-192%) and a low opsonic activity (median, 33%; range, 8-484%) at birth. During the first 2 postnatal wk IgG titers decreased significantly in septicemia patients (from a median of 30 to 17%,p= 0.025), but not in control subjects, whereas opsonic activity remained unchanged. The titer of IgG antibodies increased significantly in septicemia patients after FFP administration (from a median of 17 to 41%,p= 0.002), whereas the effect on opsonic activity was unpredictable, showing a moderate increase in 10 out of 12 infants, and in 2 patients even a substantial decrease (>50%), despite adequate opsonic activity in the corresponding FFP batches. Immunoblotting of sepsis isolates with the corresponding patient sera demonstrated that septicemic infants may generate IgG antibodies against their blood isolate. Neonates who acquire coagulase-negative staphylococcal septicemia cannot be distinguished from control subjects on the basis of IgG antibodies and opsonic activity to staphylococci either at birth or during the first 2 postnatal wk. The administration of FFP to septicemia neonates has an unpredictable effect on opsonic activity and therefore does not seem to be a useful addition to antibiotic therapy.Abbreviations: FFP,fresh frozen plasma;IVIG,i.v. immunoglobulin;PMN,polymorphonuclear neutrophils;GHBSS,gelatin in Hanks' balanced salt solution;cfu,colony-forming unit

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Catecholamines trigger the switch from liquid secretion to absorption by perinatal lung, but regulation of Cl-and liquid secretion by pulmonary epithelia early in lung development (low [catecholamine]) is unknown. We looked for evidence for P1and P2receptors that mediate Cl-secretion in 14-d distal lungs and 14- and 18-d tracheas explanted from fetal rats (term = 22 d). We measured amiloride-insensitive transepithelial voltage changes induced by ATP, UTP, or adenosine. Explants were hyperpolarized by all three agonists and by terbutaline, aβ-adrenergic agonist and Cl-secretagogue. Whereas adenosine, ATP, or UTP injected into 14-d explant lumena, or adenosine added to the tracheal bath, induced hyperpolarization with EC50of 2-15 μM EC50, values for all three agonists in the distal lung bath or ATP or UTP in the tracheal bath were five times greater. By 18 d, EC50values for agonists in the bath were comparable to those for lumenal agonists (3-12μM). In contrast, microinjection of terbutaline into all explant lumena(final concentrationn = 3 × 10-5M) induced minimal hyperpolarization, whereas the same concentration in the bath raised bioelectric potential difference maximally. We conclude that1)β-adrenergic receptors are present on the basolateral membranes of cells of the pulmonary epithelium early in lung development, and2) adenosine, ATP, and UTP receptors are present in apical membranes throughout lung epithelial development, but basolateral receptors for these agaonists in distal lung or ATP/UTP in trachea function later in gestation. The putative distribution of P1and P2receptors suggests a role for agonists released from pulmonary epithelial cells in the regulation of liquid secretion early in lung development.Abbreviation: PD,potential difference (bioelectric)

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

PTH-related protein (PTHrP) is found with its receptor in a variety of normal mammalian embryonic tissues where it apparently regulates cellular growth and differentiation. PTHrP stimulates phosphatidylcholine synthesis in rat fetal lung explants, suggesting a role in fetal type II alveolar maturation and surfactant production. We investigated PTHrP levels in tracheal aspirates of newborn infants. We collected tracheal aspirates from 40 intubated newborn infants within the first 24 h of life. PTHrP levels were measured by a RIA using rabbit antisera to PTHrP peptide 38-64. We found significantly lower PTHrP levels in tracheal aspirates from infants born at less than 35 wk of gestation (p= 0.02) and with a birth weight less than 2 kg (p= 0.04). We also found significantly lower PTHrP levels in male preterm (<35 wk of gestation) infants compared with female infants(p= 0.01), and in preterm infants who required multiple doses of surfactant (p= 0.005). Preterm infants exposed to antenatal steroids had significantly higher levels of PTHrP in tracheal aspirates(p= 0.02). PTHrP is associated with various indices of lung maturation and may prove to be a mediator of differentiation and growth.Abbreviations: PTHrP,PTH-related protein;RDS,respiratory distress syndrome;TP,total protein

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Synthetic surfactant peptides offer an opportunity to standardize the protein composition of surfactant. We tested the effect of phospholipids (PL) with synthetic full-length SP-B1-78(B), mutant B (Bser), KL4peptide (UCLA-KL4), and palmitoylated SP-C1-35(C) on oxygenation and lung function in a surfactant-deficient rat model. Sixty-four adult rats were ventilated with 100% oxygen, a tidal volume of 7.5 mL/kg, and a rate of 60/min. Their lungs were lavaged with saline until the arterial PO2dropped below 80 torr, when 100 mg/kg surfactant was instilled. Surfactant preparations included: PL (PL surfactant), PL + 3% B (B surfactant), PL + 3% B and 1% C (BC surfactant), PL + 3% UCLA-KL4(KL4surfactant), PL + 3% Bser (Bser surfactant), and PL + 3% B and 1% UCLA-KL4(BKL4surfactant). Sixty minutes after surfactant instillation, positive end-expiratory pressure was applied for 5 min, and pressure-volume curves were determinedin situ. The six surfactant preparations had a minimum surface tensions <10 mN/m on a Langmuir/Wilhelmy balance. Instillation of PL, Bser, and BKL4surfactant increased mean arterial/alveolar PO2(aADO2) ratios by 50-100% over postlavage values, whereas KL4surfactant increased aADO2ratios by 118%, B surfactant by 191%, and BC surfactant by 225%. Lung volumes at 30 cm H2O pressure were highest after treatment with BC surfactant, intermediate after B and KL4surfactants, and lowest after BKL4, Bser, and PL surfactants. These data suggest that a surfactant preparation with a combination of synthetic B and C peptides surpasses synthetic B and KL4surfactants in improving oxygenation and lung compliance in surfactant-deficient rats.Abbreviations: aADO2,arterial/alveolar PO2ratio;DPPC,dipalmitoyl phosphatidylcholine;FIO2,fraction of inspired O2;PA,palmitic acid;Pao,arterial partial pressure of O2;PaCO2,arterial arterial partial pressure of CO2;PEEP,positive end-expiratory pressure;PL,phospholipid;POPG,1-palmitoyl-2-oleoyl phosphatidyl glycerol;SP,surfactant protein;PG,phosphatidyl glycerol;Fmoc,N-(9-fluorenyl)methoxycarbonyl

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A characteristic of perinatal encephalopathies are the distinct patterns of neuronal and glial cell loss. Cerebral hypoperfusion is thought to be a major cause of these lesions. Gestational age is likely to influence outcome. This study compares the cortical electrophysiologic and histopathologic responses to hypoperfusion injury between preterm and near term fetuses. Chronically instrumented 0.65 (93-99-d,n= 9) and 0.9 (119-133-d,n= 6) gestation fetal sheep underwent 30 min of cerebral hypoperfusion injury. The parasagittal cortical EEG and impedance (measure of cytotoxic edema) responses plus histologic outcome (3 d) were compared. The acute rise in impedance was similar in amplitude, but the onset was delayed (5.0 ± 0.7versus9.1 ± 1.1 min,p< 0.05) in the preterm fetuses relative to those near term. In contrast the extent of the secondary rise was reduced (p< 0.01) and peaked earlier in the preterm fetuses (19.8 ± 1.0versus40.5 ± 3.5 h,p< 0.01). Both groups had a similar fall in EEG spectral edge frequency. The preterm fetuses had a milder loss of EEG intensity at 72 h(-7.7 ± 1.5versus-12.8 ± 0.9 dB,p< 0.05). At both ages there was a predominantly parasagittal cortical distribution of damage with a similar pattern of neuronal loss in the thalamus and striatum. There was extensive selective neuronal loss within the upper layers of the cortex in those near term. In contrast the preterm fetuses developed subcortical infarcts (p< 0.05). The cortical response to injury altered during the last trimester. The results suggest the severity of the delayed phase of cortical neuronal injury and selective neuronal loss increased near term. In contrast, the preterm fetuses had a more rapidly evolving injury leading to necrosis of the subcortical white matter.Abbreviations: CI,cortical impedance;dB,decibel;Δ,delta or change;PaCO2,partial pressure of arterial carbon dioxide;PaO2,partial pressure of arterial oxygen

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Immunohistochemical techniques were used to examine the distribution of prostaglandin H synthase (PGHS)-2 and neuronal nitric oxide synthase (nNOS) in piglet brain. Samples from parietal cortex, hippocampus, and cerebellum were immersion fixed in 10% formalin, sectioned at 50 μm, and immunostained using specific antibodies against PGHS-2 and nNOS. Immunoreactivity for PGHS-2 was extensive throughout the areas examined. For example, PGHS-2 immunoreactive cells were present in all layers of the cortex, but were particularly dense among neurons in layers II/III, V, and VI. In addition, glial cells associated with microvessels in white matter showed PGHS-2 immunoreactivity. In contrast, nNOS immunoreactive neurons were limited in number and widely dispersed across all layers of the cortex and thus did not form a definable pattern. In the hippocampus, heavy PGHS-2 immunoreactivity was present in neurons and glial cells in the subgranular region, stratum radiatum, adjacent to the hippocampal sulcus, and in CA1 and CA3 pyramidal cells. Immunostaining for nNOS displayed a different pattern from PGHS-2 in the hippocampus, and was mainly localized to the granule cell layer of the dentate gyrus and the mossy fiber layer. In the cerebellum, PGHS-2 immunoreactivity was heavily represented in the Bergmann glia and to a lesser extent in cells of the granular layer, whereas nNOS was detected only in Basket cells. There are four conclusions from this study. First, PGHS-2 immunoreactivity is widely represented in the cerebral cortex, hippocampus, and cerebellum of neonatal pigs. Second, glia cells as well as neurons can show immunoreactivity for PGHS-2. And third, the distribution of nNOS is different from PGHS-2 immunoreactivity in the cerebral cortex, hippocampus, and cerebellum.Abbreviations: PGHS,prostaglandin H synthase;NOS,nitric oxide synthase;PGH2,prostaglandin H2;NO,nitric oxide;NGS,normal goat serum;GFAP,glial fibrillary acidic protein

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We tested the hypothesis that hypoxic newborn piglets can be successfully resuscitated with lower O2concentrations than 21%. Severely hypoxic, 2-4-d-old, anesthetized piglets were randomly divided into five resuscitation groups: 21% O2(n= 10), 18% O2(n= 9), 15% O2(n= 9), 12% O2(n= 8), all normoventilated, and a hypoventilated 21% O2group (PaCO2; 7.0-8.0 kPa,n= 9). Base excess (BE) reached -20 ± 1 mmol/L at the end of hypoxia. After 3 h of resuscitation, BE had risen to -4 ± 1 mmol/L in the 21% O2, 18% O2, and hypoventilated groups, but was -10 ± 2 mmol/L in the 15% O2group (p< 0.05versus21% O2group) and -22 ± 2 mmol/L in the 12% O2group (p< 0.05versus21% O2group). Four animals died during resuscitation, all allocated to the 12% O2group (p< 0.05versus21% O2group). Somatosensory evoked potentials (SEPs) recovered in 39 of 45 piglets, and remained present during resuscitation in all except the 12% O2group. SEP recovered initially even in six of eight animals in the 12% O2group, but disappeared again in all later during resuscitation. The SEP amplitude recovered to levels not significantly different from the 21% O2group in all groups except the 12% O2group. Plasma hypoxanthine concentrations and extracellular hypoxanthine concentrations in the striatum decreased during resuscitation to levels not significantly different from the 21% O2group in all but the 12% O2group(p< 0.05versus21% O2group). In conclusion, severely hypoxic newborn piglets were resuscitated as efficiently with both hypoventilation and 18% O2as with 21% O2.Abbreviations: BE,base excess;CaO2,arterial O2content;CVSSO2,venous O2content from the sagittal sinus;FIO2,inspired fraction of O2;MABP,mean arterial blood pressure;PaCO2,arterial CO2tension;PaO2,arterial O2tension;SEP,somatosensory evoked potential

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Failure to arouse from sleep is a possible mechanism leading to sudden infant death. Using a controlled pulsatile air jet applied alternately to the nostrils we have made multiple measures of arousal threshold both between and within sleep states. Infants (n= 22) born at term were studied at 2-3 wk postterm (mean age 13 d, range 9-17 d, study 1) and again at 2-3 mo postterm (mean age 78 d, range 56-98 d, study 2). Arousal threshold (stimulus driving pressure, cm H2O) was determined in both active sleep (AS) and quiet sleep (QS). At both ages arousal threshold in QS was significantly higher (251 ± 24 and 298 ± 35) than in AS (163 ± 19 and 144 ± 29) (p< 0.001). In a morning sleep period, the first and second QS epochs were compared in each baby. In both study 1 and study 2, respectively, arousal thresholds were significantly higher in the second QS epoch (270 ± 34 and 497 ± 100) than in the first QS epoch (198 ± 29 and 252 ± 69) (p< 0.05 andp< 0.02). There was a significant correlation in individual infants between arousal thresholds in the two states at both ages (p< 0.005 andp< 0.007, respectively). Regression analysis showed no correlation between the length of time the infant had been in a particular sleep state and the arousal threshold in either state in study 1 or in AS in study 2; however, arousal threshold increased significantly(p< 0.01) with time in QS in study 2. This study has expanded on previous findings that arousability is sleep state-dependent by demonstrating that arousability in QS is also altered by the length of time that the infant has been asleep.Abbreviations: SIDS,sudden infant death syndrome;QS,quiet sleep;AS,active sleep;HR,heart rate;SaO2,oxygen saturation

ISSN:0031-3998    

出版商:OVID    

年代:1998

数据来源: OVID