摘要:

Adhesion molecules play a major role in the recruitment of neutrophils to the site of inflammation. Neutrophils' localization is dynamic and involves multiple steps. In each step a different family of adhesion molecules takes part. The rolling phase is mediated by the selectin family, the E-, L-, and P- selectins, and their ligand, sialyl Lewis X. The next step, the activation and firm adhesion of the neutrophils to the endothelium, is regulated by the integrin family and their ligand, the Ig superfamily. The final step of transendothelial migration is again mediated by these two families of adhesion molecules. Although manyin vitrostudies were able to show the role of these molecules, their real importance was demonstrated in rare disease states where one of the adhesion molecule was absent. Two adhesion molecule deficiencies were described, both characterized by recurrent infections, defect in wound healing, and marked leukocytosis. Leukocyte adhesion deficiency (LAD) I is caused by a defect in the β subunit of the integrin molecule, whereas in LAD II, the ligand for the selectin, the sialyl Lewis X is markedly decreased. Further insight was also gained with the generation of strains of mice deficient in one or another adhesion molecules (knock-out mice) Exploiting current knowledge on adhesion molecules and their role in health and disease, several trials have been designed to assess the effect of blocking their activity in conditions associated with increased expression of various adhesion molecules.Abbreviations: LFA-1,lymphocyte-associated antigen-1;Mac-1,macrophage antigen-1;VLA,very late antigen;VCAM,vascular cell adhesion molecule;ICAM,intercellular adhesion molecule;SLeX,sialyl Lewis X;LAD,leukocyte adhesion deficiency;TNF,tumor necrosis factor

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Two experiments determined behavioral effectiveness of β-casomorphins(β-CM) in 10-d-old rats by evaluating changes in heat escape latency from a 48°C stimulus applied to a forepaw. In one study rats were injected systemically with β-CM4, -5, or -7 at a dose range of 0.1-2.5 mg/kg. Onlyβ-CM5 was effective, and the dose-response relationship was graded. The second study evaluated the locus of action of β-CM5 through two experimental manipulations: first, by injecting it (0.25 μg) into the lateral ventricles and by attempting to block its effects with systemic injections of naloxone. Second, rats received intracerebroventricular injections of naloxone (0.25 μg) and systemic injections of β-CM.β-CM was effective centrally, suggesting central detection of the drug. Naloxone injected into the lateral ventricles blocked the effects of systemic administration of β-CM, implying that circulating β-CM or their precursors cause behavioral change through central mechanisms.Abbreviations: β-CM,casomorphin;ICV,intracerebroventricular;i.p.,intraperitoneal

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The role of superoxide radical formation in the pathogenesis of perinatal hypoxic-ischemic injury was examined using transgenic (Tg) mice expressing three times normal amounts of copper/zinc-superoxide dismutase (CuZn/SOD). Fourteen litters of postnatal d 7 strain 218/3 mice were subjected to right common carotid artery ligation followed by 90 min of hypoxia in an 8% oxygen/humidified chamber maintained at 37°C. Both Tg mice (n= 32) and their nontransgenic (nTg) littermates (n= 30) survived the injury equally. Evaluation of infarcted brain areas measured by video image analysis of three coronal brain sections through the anterior hippocampus from each animal revealed that the Tg animals suffered brain infarction more frequently than did nTg mice. Blinded histologic scoring of cerebral cortex and striatum 5 d after injury revealed that Tg mice were more likely to have higher histologic severity scores than their nTg littermates (p= 0.0463, Mann-WhitneyUtest). These findings suggest that brain injury in perinatal hypoxia-ischemia may be mediated in part by free radical formation from excessive hydrogen peroxide or nitric oxide production.Abbreviations: Tg,transgenic;nTg,nontransgenic;SOD,superoxide dismutase;GSH,reduced glutathione;NOS,nitric oxide synthase

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The objective of this study was to compare the effect of extracorporeal membrane oxygenation (ECMO) on cerebral oxygenation and hemodynamics in normoxemic and hypoxemic piglets. Six hypoxemic and six normoxemic piglets were put on venoarterial ECMO after cannulation of the right common carotid artery and external jugular vein with careful priming to avoid hemodilution. Changes in cerebral concentrations of oxyhemoglobin (cO2Hb), deoxyhemoglobin (cHHb), (oxidized-reduced) cytochromeaa3(cCyt.aa3), and blood volume(CBV) were continuously measured by near infrared spectrophotometry. Heart rate, arterial O2saturation (Sao2), arterial blood pressure, pulsatility ratio of systemic circulation (calculated as systolicdiastolic/mean arterial blood pressure), central venous pressure, intracranial pressure, and left common carotid artery blood flow (LCaBF) were simultaneously measured. We found that the cannulation procedure resulted in increased CBV,cHHb, and LCaBF in both groups. At 60 and 120 min after starting ECMO, the values ofcO2Hb, CBV, and LCaBF in both groups were significantly higher than precannulation values, while the pulsatility ratio decreased. In the hypoxemic groupscHHb decreased and Sao2increased as well. No significant changes of other variables were found. Between hypoxemic and normoxemic groups no significant differences in the response of CBV and LCaBF at 60 and 120 min were found. We conclude that in piglets cannulation for ECMO resulted in cerebral venous congestion and compensated increase in LCaBF. After starting ECMO, the cerebral O2supply increased due to increased arterial O2content. It was accompanied by similar increase of CBV in both groups, probably as a result of hyperperfusion, which seems to be related to the ECMO procedure itself.Abbreviations: ECMO,extracorporeal membrane oxygenation;NIRS,near infrared spectrophotometry;CBF,cerebral blood flow;LCaBF,mean blood flow in left common carotid artery;CBV,cerebral blood volume;cO2Hb,oxyhemoglobin concentration;cHHb,deoxyhemoglobin concentration;ctHb,total Hb concentration;cCyt.aa3,(oxidized-reduced) cytochromeaa3concentration;cHb,arterial Hb concentration;Sao2,arterial O2saturation;MABP,mean arterial blood pressure;CVP,central venous pressure;ICP,intracranial pressure;Pao2,partial pressure of arterial O2;Paco2,partial pressure of arterial CO2

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The objective of this study was to establish longitudinal normative limits for home memory monitors during early infancy. Eighty-eight healthy infants were monitored overnight at 0.25-19 wk of age using the Healthdyne Smart Monitor. Apnea settings were 14 s for recording and 40 s for alarm; the bradycardia setting was 50 beats/min (5-s delay) for both recording and alarm. Arterial oxygen saturation (Sao2) was documented whenever an event was recorded. The monitor was used 77% of all possible days; median daily use was 8.0 h. Eighty-three percent of all monitor alarms were caused by loose leads, the other 17% by false apnea or false bradycardia. Of all recorded events, 68.9% were caused by false apnea or false bradycardia; the other 31.1% were central apneas that reached the recording threshold of 14 s. The longest apnea was 36 s (wk 1); the 95th percentile for longest apnea was 19.9 s in wk 1 and 18.0 s in wk 17-19 (p< 0.001). Periodic low Sao2values occurred with periodic breathing; the lowest value was 72%. The 5th percentiles for lowest Sao2were 82 and 86% in wk 1 and 13-19, respectively (p< 0.001), but the minimum value observed in any week was never >81%. The median duration of Sao2< 90% was only 5 s but the range was wide (1-183 s), and 39/527 episodes (7.4%) were >10 s. In summary, these longitudinal data provide the first available normal limits for cardiorespiratory pattern and Sao2during documented home monitoring in early infancy. Utilization of these normative data will improve the diagnostic validity and clinical usefulness of event recordings.Abbreviations: LARS,low amplitude respiratory signal;Sao2,arterial oxygen saturation (%);SIDS,sudden infant death syndrome

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

This study was designed to determine indirectly if the changes in ovine fetal pulmonary vascular tone caused by i.v. injections of nitric oxide-containing solutions are mediated by cGMP. We first characterized the dose-response relationship of bolus intrapulmonary injections of zaprinast (a cGMP-selective phosphodiesterase inhibitor) and nitric oxide solutions. Injections of nitric oxide solutions as well as zaprinast solutions resulted in dose-dependent decreases in pulmonary arterial pressure that were greater than reductions in systemic arterial pressure. We also evaluated the effects of simultaneous infusions of zaprinast and U46619 (a thromboxane mimetic) on the response to bolus injections of 1.0 μg of acetylcholine, 100 ng of endothelin-1, and 10.0 μL of ethanol saturated with nitric oxide. Zaprinast was infused at a rate of 1.5 mg/min, and the concentration of U46619 was titrated to raise mean left pulmonary arterial pressure (LPAP) to the steady state level that was present before infusing zaprinast. All bolus injections reduced left pulmonary arterial pressure more than they reduced mean systemic arterial pressure. However, neither the response magnitudes nor the response durations were affected by simultaneous infusions of zaprinast and U46619. We therefore suggest that modulation of fetal pulmonary vascular tone by endogenously produced nitric oxide may involve mechanisms other than raising smooth muscle cytoplasmic cGMP concentrations.Abbreviations: LPAP,mean left pulmonary arterial pressure;SAP,mean systemic arterial pressure;LPAPt1/2,time from point of injection to point when LPAP response attenuates to half peak response

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Respiratory distress syndrome (RDS) is characterized by the presence of fibrin-rich exudates in the alveoli. Fibrin and its degradation products may play an important role in the pathogenesis of bronchopulmonary dysplasia(BPD). The purpose of this study was to test the hypothesis that preterm neonates with RDS have depressed alveolar fibrinolytic activity and that those with RDS progressing to BPD have an even greater impairment in alveolar fibrinolysis. Serial tracheal aspirate (TA) samples from intubated neonates-9 control and 46 with RDS-were analyzed for fibrinolytic activity. In neonates with RDS, 26 resolved, 18 progressed to BPD, and 2 died before 28 d. Plasminogen activator (PA) and its inhibitor (PAI) were identified in TA by reverse fibrin autography and immunoblotting. Net PA/plasmin activity in TA was significantly depressed on d 1 of life in patients with self-resolved RDS(median = 20.85 ng/mL,p< 0.05) and RDS progressing to BPD(median = 4.97 ng/mL,p< 0.001) compared with control patients(median = 87.1 ng/mL). In addition, neonates progressing to BPD had significantly lower PA/plasmin activity on day one of life compared with neonates with self-resolved RDS (p< 0.001). ELISA for specific PA and PAI were not significantly different. We speculate that depressed fibrinolytic activity may place preterm neonates at risk for RDS and that the degree of this depression may predict the progression to BPD. In infants≤30 wk of gestation at birth with RDS, a PA/plasmin activity ≤10.0 ng/mL on the 1st d of life had a positive predictive value of 80% (12/15) and a negative predictive value of 82% (9/11) for the progression to BPD.Abbreviations: RDS,respiratory distress syndrome;BPD,bronchopulmonary dysplasia;TA,tracheal aspirate;PA,plasminogen activator;PAI,PA inhibitor;ELF,epithelial lining fluid;uPA,urokinase-type PA;tPA,tissue-type PA;Pao,partial pressure of arterial O2;RFA,reverse fibrin autography

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Although surfactant replacement therapy has dramatically improved the outcome of premature infants with respiratory distress syndrome, approximately 30% of treated infants show a transient or no response. Nonresponse to surfactant replacement therapy may be due to extreme lung immaturity and possibly surfactant inactivation. Surfactant inactivation involves aspecific biophysical events, such as interference with the formation or activity of an alveolar monolayer, and specific interactions with serum proteins, including antibodies, leaking into the alveolar space. As formulations containing surfactant proteins appear to better tolerate serum inactivation, we used an excised rat lung model to compare the susceptibility to serum inactivation of a mixture of synthetic phospholipids selected from surfactant lipid constituents, Exosurf (a protein-free synthetic surfactant), Survanta[containing surfactant proteins B and C (SP-B and -C)], and a porcine surfactant (containing SP-A, -B, and -C). For each of these preparations, we used pressure/volume determinations as anin situmeasure of surfactant activity and retested the same preparations after mixing with human serum, a nonspecific surfactant inactivator. Human serum inactivated porcine surfactant to a lesser extent than Survanta, Exosurf, or synthetic phospholipids. Temperature exerted a significant effect on deflation stability, as shown by a greater lung compliance in untreated, normal lungs and a larger improvement in compliance after treating lavaged lungs with synthetic phospholipids at 37°C than at 22°C. We conclude that surfactant containing SP-A, -B, and -C is only moderately susceptible to inactivation with whole serum and may therefore exert a greater clinical response than protein-free surfactants or those containing only SP-B and-C.Abbreviations: PL,phospholipids;RDS,respiratory distress syndrome;SP,surfactant protein

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Maternal diabetes during pregnancy is associated with increased risk of neonatal respiratory distress syndrome (RDS). Previous studies using rat models for the diabetic pregnancy have documented decreased amounts of surfactant protein mRNA in the lungs of fetuses. In this study, we measured fetal lung surfactant-associated protein A (SP-A) mRNA from diabetic rats treated with insulin by daily injection or osmotic pump. Lungs were taken from fetuses on gestational d 20, and RNA was isolated and subjected to Northern blotting and densitometry to quantify SP-A mRNA. Fetal lung SP-A mRNA from untreated diabetic pregnancies was 34 ± 2.9% of control. Insulin treatment increased levels to 55 ± 4.2% of control values. Fetal lung SP-A mRNA levels were affected by the timing, length, and effectiveness of insulin treatment. Although levels from all treatment groups were still less than control values, insulin treatment during the last 5 or 10 d of pregnancy resulted in a substantial increase in SP-A mRNA levels over those of from untreated diabetic pregnancies. However, fetuses from the group with insulin treatment for the entire pregnancy showed decreases in fetal SP-A mRNA levels. Although the mechanism(s) responsible for the effects of diabetes and its treatment on fetal SP-A expression remain unclear, it appears unlikely that hyperglycemia is the principal cause.Abbreviations: SP-A,surfactant protein A;RDS,respiratory distress syndrome;STZ,streptozotocin

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The purpose of this study was to describe cytokine profiles of human neonatal pulmonary cells isolated by tracheal aspiration (TA) and by deep pulmonary lavage (DPL). We hypothesized that mRNA phenotyping, using the technique of reverse transcriptase polymerase chain reaction (RT-PCR), would reveal differences in cytokine expression patterns between cells from proximal and distal airway compartments. We reasoned that cells derived by DPL may reflect pathogenic pathways indicative for the development of bronchopulmonary dysplasia in the premature infant. Here we have described the detection of mRNA for IL-1α, IL-1β, IL-6, IL-8, and tumor necrosis factor-α. Fourteen paired TA and DPL samples from six premature infants were collected at 1, 7, or 28 d of age. Two of 14 samples were negative forβ-actin (a ubiquitous mRNA) by RT-PCR and were excluded from further analysis. Each of the remaining 12 samples expressed IL-8. Furthermore, each cytokine could be expressed by TA or DPL cells. Cytokine mRNA phenotype profiles were found to differ between TA and DPL cells in four of five paired samples. Our results show that cells retrieved from these two pulmonary compartments are sources for these cytokines and suggest that RT-PCR of TA/DPL cells can be used to test hypothetical predictive markers for the development of bronchopulmonary dysplasia.Abbreviations: BAL,bronchoalveolar lavage;BPD,bronchopulmonary dysplasia;DPL,deep pulmonary lavage;RT,reverse transcriptase;PCR,polymerase chain reaction;TA,tracheal aspirate;TNF-α,tumor necrosis factor-α

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID