摘要:

Leukotrienes (LT) comprise a group of biologically highly potent lipid mediators synthesized by 5-lipoxygenase from 20-carbon polyunsaturated fatty acids, predominantly arachi-donate (1–3). They include the cysteinyl LT, LTC4, LTD4, LTE4, representing biologically active constituents of the long-known “slow-reacting substance of anaphylaxis” and the dihy-droxyeicosatetraenoate, LTB4. LT act at nanomolar concentrations in intercellular communication, signal transduction and on host defense. Extensive studies during the last years have demonstrated that LT are not only locally acting mediators but also systemically acting substances.Recent progress in LT research has led to a more detailed understanding of their biosynthesis, degradation, and inactivation. Moreover, the pathogenetic role of LT in various human diseases has become recognized, and inhibitors of biosynthesis as well as receptor antagonists interfering with signal transduction were developed.The aims of the review are1) to update the current knowledge of the synthesis, metabolism, and principal role of LT as mediators under physiologic and pathologic conditions;2) to give a brief overview about the development, state of the art, and limitations of analytical techniques;3) to discuss clinical conditions with particular emphasis on pediatric diseases in which LT are assumed to play a pathobiologic role;4) to illustrate how present knowledge has influenced current pathophysiologic concepts; and5) to briefly present future aspects of biochemical and clinical research on LT.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Cerebral vasodilation in response to hypotension is necessary to maintain adequate cerebral blood flow. This study in newborn pigs examines the hypothesis that endothelial injuryin vivoinhibits cerebral vasodilation in response to hypotension in newborn pigs, thus suggesting that this response is endothelium dependent. Chloralose-anesthetized piglets with closed cranial windows were studied before and after injury caused by light/dye or before and after dye only sham control. Light/dye injury was produced by injecting sodium fluorescein i.v. and passing filtered light from a mercury arc lamp though the cranial window. Measurements of pial arteries and arterioles were made during normotensive and hypotensive periods. Hemorrhagic hypotension (to 50% of the mean arterial control value) caused pial arterial and arteriolar diameters to increase 49 ± 8% and 66 ± 8%, respectively. After the light/dye injury, dilation in response to hypotension was absent, whereas dilations in response to isoproterenol and constriction in response to hypertension (3.33 to 4.0 kPa increase in arterial pressure) and hypocapnia were retained. These findings are consistent with the hypothesis that hypotension-induced cerebral arteriolar vasodilation is dependent on endothelial signals influencing adjacent smooth muscle.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Arousal at birth is likely to be accompanied by changes in gene expression patterns in the brain. We analyzed the expression levels of genes that may be involved in neonatal adaptation. We have also tried to dissect the effect of hypoxia and hypothermia, two components that may play a role in gene expression at birth. Therefore, we analyzed the expression patterns of thec-fos, tyrosine hydroxylase, enkephalin, preprotachykinin-A, and neuropeptide Y genes in various brain regions of rat pups at various time points after cesarean section under normal conditions and after exposure to hypoxia and hypothermia. We found thatc-fosRNA was up-regulated transiently after birth in neocortex, mid-brain, and pons-medulla with a maximum of 30 min after cesarean section, and that this transient increase was not further augmented by hypoxia and hypothermia. The expression patterns of the other genes were not significantly altered, with the exception of a very slight increase in tyrosine hydroxylase RNA levels. We discuss tentative mechanisms for the transient increase inc-fosexpression and the possible involvement of catecholamines in this process.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Surfactant apoprotein A (SP-A) reduces the inhibitory effects of plasma proteins on the surface tension lowering properties of pulmonary surfactantin vitro.To test the effects of SP-Ain vivowe administered a complete natural dog lung surfactant (DLS) containing apoproteins SP-A, SP-B, and SP-C, a butanol extract of DLS (DLSE) containing only apoproteins SP-B and SP-C, and DLSE supplemented with SP-A intratracheally to prematurely delivered rabbit pups in the presence of increasing amounts of human plasma. In the absence of plasma DLS and DLSE (100 mg/kg phospholipid) had comparable effects on lung mechanics (compliance during ventilation with a tidal volume of 6–7 mL/kg and quasi-static pressure-volume behavior) in this surfactant deficiency model. Plasma proteins in increasing amounts to a maximum protein concentration of 62.5 mg/mL had no effect on the response of the pups to DLS. In contrast, plasma added to DLSE in concentrations above 20 mg/mL significantly increased the peak inspiratory pressure (PIP) required to ventilate the pups with a tidal volume of 6–7 mL/kg, reduced the calculated total lung compliance, and decreased the deflation lung volumes. The inhibitory effects of plasma on DLSE were significantly less when SP-A was added to DLSE (5:1, phospholipid:SP-A, wt:wt). The addition of SP-A to DLSE in plasma restored the activity of the extract to levels comparable to complete DLS. These results suggest that plasma can interfere with surfactant function and that SP-A has a significant protective effect for surfactant against the inhibitory effects of plasmain vivo.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The risk of pulmonary hemorrhage is increased in extremely low birth weight infants treated with surfactant. The pathogenesis of this increased risk is far from clear. We tested whether exposure of cell membranes to surfactant may lead to increased membrane permeability, hypothesizing that this process may contribute to the occurrence of alveolar hemorrhage after surfactant treatment. Aliquots of washed packed red blood cells (used as membrane model) were suspended in 0.9% NaCl with various concentrations of Survanta or Exosurf for either 2 or 24 h at 37°C. Cytolysis was measured by spectrophotometric determination of free Hb after centrifugation. Red cells suspended in 0.9% NaCl alone, distilled water, or various concentrations of melittin were used as negative and positive controls. Both surfactants were associated with increased hemolysis to 35% of maximum at concentrations of 1.25 mg/2 mL. Above these concentrations, Survanta was associated with no increase in hemolysis, whereas Exosurf increased hemolysis to 60% of maximum at concentrations of 12.5 mg/2 mL. In additional experiments, primary cultures of alveolar type II cells from adult rats were treated with Survanta, Exosurf, the Exosurf components tyloxapol and hexadecanol, melittin, or culture medium alone. After 24 h of incubation, lactate dehydrogenase release into the media was measured as a percent of total lactate dehydrogenase activity to indicate cytotoxicity. Lactate dehydrogenase release was <10% for control experiments but increased sharply with Exosurf and its components tyloxapol and hexadecanol. These results indicate that surfactant may be associated within vitrocytotoxicity and that this property differs for different surfactants and different dosages.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Persistent pulmonary hypertension of the newborn (PPHN) often requires extracorporeal membrane oxygenation (ECMO), during which time pulmonary vascular resistance gradually declines. Nitric oxide (NO) is a recently recognized pulmonary vasodilator, but its role in PPHN is unknown. We tested the hypothesis that the concentrations of the urinary metabolites of NO,i.e.nitrite and nitrate, are reduced in patients with PPHN and increase during ECMO as the PPHN resolves. Eight newborn infants with PPHN on ECMO were studied. Daily urinary concentrations of nitrite/nitrate were measured. We found that mean urinary concentrations of nitrite/nitrate were lower in patients with PPHN than in 47 controls without pulmonary disease (p< 0.005). Urinary nitrite/nitrate concentration showed an initial increase after initiation of ECMO. However, a decrease to concentrations still lower than controls occurred on the day before decannulation. We conclude that intrinsic NO production is significantly lower in patients with PPHN than in controls but increases with oxygenation. We speculate that decreased urinary NO metabolite concentrations imply a role for NO deficiency in the pathogenesis of PPHN.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This study was designed to test the hypothesis that inhalation of nitric oxide by lambs delivered prematurely would result in increased systemic arterial blood oxygen tension and decreased pulmonary vascular resistance. Eleven premature fetal lambs were delivered by cesarean section at 126–127 d gestation. One hundred min after the onset of ventilation, nitric oxide gas was added to the lambs' breathing mixture. The animals were exposed in random order to 5 ppm for 10 min, 20 ppm for 10 min, and 20 ppm for 20 min. Each treatment period was preceded by and followed by a 10-min washout period. When compared with the washout (control) periods, all three treatment periods resulted in an improvement in both the systemic arterial blood oxygen tension and the physiologic intrapulmonary shunt. Inhalation of nitric oxide also resulted in a selective decrease in pulmonary arterial blood pressure. Comparisons between the different treatment groups revealed a further improvement in blood oxygenation and pulmonary hemodynamics when using the higher concentration of nitric oxide. Interestingly, the rise in arterial blood oxygenation continued after inhaling 20 ppm nitric oxide for more than 10 min.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A series of experiments were designed to examine the potential cytotoxicity of nitric oxide (NO), or reactive species derived from NO, in HA1 fibroblasts and H2O2-resistant variants of this cell line, designated OC14 cells. A 1-h exposure at 37°C to a 1.7 mM bolus dose of NO, prepared in N2-gassed medium, significantly reduced clonogenic survival in the HA1 fibroblasts line to 60% of control cells treated with N2-gassed medium alone. The OC14 cells were found to be completely resistant (100% survival) to NO-mediated injury in comparable experiments. A second set of experiments was designed to determine the role of the intracellular antioxidant, glutathione, in protection against NO-mediated injury. Depletion of total glutathione resulted in a significant reduction in HA1 and OC14 clonogenic survival to 8% and 50% when compared with respective control cells. The effect of total glutathione depletion on NO-initiated toxicity in HA1 cells was dose- and cell-density dependent and was observed to occur within 5 min of exposure to NO. Further evidence of cytotoxicity was demonstrated by loss of trypan blue dye exclusion properties in glutathione-depleted HA1 cells after NO exposure. Other experiments demonstrated that nitrate and nitrite exposure produced no cytotoxicity in glutathione-depleted HA1 cells and that coincubation of NO-saturated medium with oxyhemoglobin inhibited NO-induced cytotoxicity in glutathione-depleted HA1 cells. These results demonstrate that1) nitric oxide, or an NO-derived reactive nitrogen species other than nitrites or nitrates, is responsible for reduction in clonogenic survival and trypan blue dye exclusion capabilitiesin vitro; 2) biochemical pathways associated with cellular resistance to oxidative stress also confer resistance to NO-mediated injury in this cell model; and3) total glutathione content determines a significant portion of cell sensitivity to NO-mediated cytotoxicity.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID