Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD14 functions as a cell surface receptor for endotoxin (lipopolysaccharide [LPS]) and is thought to have an essential role in innate immune responses to infection. Previous studies have revealed attenuation of the systemic response after sepsis by blocking CD14. In this study, we tested the hypothesis that CD14 blockade protects against inflammatory responses associated with LPS pneumonia. We examined the effect of an anti-murine CD14 monoclonal antibody (4C1) on the development of acute lung injury induced by intratracheal LPS in mice. We also measured the production of cytokines (tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2) and nitric oxide by murine peritoneal macrophages exposed to LPS in vitro. Nuclear factor (NF)-kappa B translocation was evaluated in nuclear extracts from lung homogenates. 4C1 significantly attenuated pulmonary edema and neutrophil emigration after LPS administration. The production of cytokines and nitric oxide by LPS-stimulated macrophages was significantly decreased by 4C1 treatment. NF-kappa B translocation induced by LPS instillation was also suppressed by 4C1. These results suggest that blockade of CD14 might attenuate acute lung injury after intratracheal instillation of LPS through the suppression of NF-kappa B translocation. The inhibitory effect of CD14 blockade on cytokine production and nitric oxide release of macrophages might contribute to the attenuation of lung injury.
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PMID:Effect of CD14 blockade on endotoxin-induced acute lung injury in mice. 1263 39

Congestive heart failure results in cardiovascular dysfunction and diminished vascular nitric oxide (NO) production. We hypothesized that overexpression of endothelial NO synthase (eNOS) within the endothelium would reduce the extent of contractile dysfunction in a murine model of infarct-induced congestive heart failure. We generated transgenic (TG) mice overexpressing the human eNOS gene. The TG mice displayed significantly enhanced eNOS protein levels and eNOS activity levels (10- to 12-fold greater) in the aorta and the coronary vasculature. Non-TG (NTg) and eNOS TG mice were subjected to permanent left anterior descending coronary artery occlusion and then observed for 1 mo. We assessed cardiac function in vivo by using echocardiography and ultraminiature ventricular pressure catheters. Myocardial infarct size was similar between study groups (approximately 70% of the risk zone). Survival was increased by 43% in the eNOS TG mice compared with NTg (P < 0.05). Fractional shortening and cardiac output were also significantly (P < 0.05) greater in the eNOS TG than in NTg. Interestingly, pulmonary edema was evident only in NTg mice, and no evidence of pulmonary edema was observed in the eNOS TG mice. Thus, targeted overexpression of the eNOS gene within the vascular endothelium in mice attenuates both cardiac and pulmonary dysfunction and dramatically improves survival during severe congestive heart failure.
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PMID:Endothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice. 1267 84

One essential factor in the development of high altitude pulmonary edema (HAPE) is elevated pulmonary artery pressure, possibly due to a lack of nitric oxide (NO) in pulmonary vessels. NOS3 gene polymorphisms (G894T, T-786C, and CA-repeats > or =38) might be linked to decreased NO synthesis and increased susceptibility to HAPE, while the C242T polymorphism of the CYBA gene [encoding for the NAD(P)H oxidase subunit p22phox] may increase NO availability and thus convey resistance to HAPE. To test this hypothesis, we genotyped 51 mountaineers susceptible and 52 mountaineers not susceptible to HAPE. Genotyping revealed similar genotype frequencies of the G894T and the T-786C NOS3 polymorphism in both groups (G894T: susceptibles, 39.2% GG, 47.1% GT, 13.7% TT; nonsusceptibles, 48.0% GG, 44.0% GT, 8.0% TT; p = 0.54. T-786C: susceptibles, 45.1% TT, 39.2% TC, 15.7% CC; nonsusceptibles, 53.8% TT, 40.4% TC, 5.8% CC; p = 0.28). Genotype frequencies of the C242T CYBA polymorphism were 43.1% CC, 47.1 % CT, and 9.8% TT in HAPE susceptibles and 38.0% CC, 52.0 % CT, and 10.0% TT (p = 0.92) in nonsusceptibles. There was also no difference between the two groups in the number of CA repeats (p = 0.57), and individuals with > or =38 CA repeats were not more likely to develop HAPE (p = 1.0). Haplotype analysis for the NOS3 polymorphisms also revealed no association with HAPE. The results of this study suggest that none of these genetic variants plays a substantial role in the pathogenesis of HAPE in Caucasians, but does not exclude epistatic effects that might still involve the genetic systems studied here.
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PMID:Lack of evidence for association of high altitude pulmonary edema and polymorphisms of the NO pathway. 1456 Dec 41

Acute respiratory distress syndrome (ARDS) can be associated with various disorders. Among these, coronavirus infection may cause life-threatening severe acute respiratory syndrome (SARS). In this review, we present animal models and techniques for the study of ARDS, and discuss the roles and possible mechanisms of various chemical factors, including nitric oxide (NO). Our early work revealed that cerebral compression elicits severe hemorrhagic pulmonary edema (PE), leading to central sympathetic activation that results in systemic vasoconstriction. The consequence of systemic vasoconstriction is volume and pressure loading in the pulmonary circulation. Vasodilators, but not oxidant radical scavengers, are effective in the prevention of centrogenic PE. In isolated perfused lung, exogenous and endogenous NO enhances lung injury following air embolism and ischemia/reperfusion. In contrast, NO synthase (NOS) inhibitors reverse such lung injury. Although NO is important in maintaining vasodilator tone, hypoxia-induced pulmonary vasoconstriction is accompanied by an increase instead of a decrease in NO release. In animal and isolated lung studies, endotoxin produces acute lung injury that is associated with increases in cytokines and inducible NOS mRNA expression, suggesting that NO is toxic to the lung in endotoxin shock. Recently, we reported several rare cases that indicate that ARDS in patients with Japanese B encephalitis, lymphangitis with breast cancer and fat embolism is caused by different mechanisms. Our early and recent studies on ARDS and PE may provide information for clinical practice and the understanding of the pathogenesis of SARS.
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PMID:Acute respiratory distress syndrome. 1457 60

Acute respiratory distress syndrome (ARDS), which was first described by Ashbaugh in 1967, consists of acute hypoxemic respiratory failure (PaO2/FiO2< or =200) associated with bilateral infiltrates on the chest radiograph caused by noncardiac diffuse pulmonary edema. Although ARDS is of multiple etiology, pulmonary or extrapulmonary injury can produce systemic inflammatory response that perpetuates lung disturbances once the initial cause has been eliminated. Most patients with ARDS require mechanical ventilation. Currently, the old standard is conventional ventilation optimized to protect against ventilator-associated lung injury. Other mechanical ventilation strategies such as high-frequency oscillatory ventilation, which is also based on alveolar recruitment and adequate lung volume, can be useful alternatives. In this review, the level of evidence for other therapies, such as prone positioning, nitric oxide and prostacyclin inhalation, exogenous surfactant, and extracorporeal vital support techniques are also analyzed.
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PMID:[Ventilation in special situations. Mechanical ventilation in acute respiratory distress syndrome/acute pulmonary lesion]. 1464 23

High-altitude pulmonary oedema (HAPE) is a potentially fatal condition affecting fit and previously well individuals at altitudes in excess of 3000 m. This article discusses the mechanisms of HAPE, considers the contribution of hypoxic pulmonary vasoconstriction and alterations in sodium transport to the pathological process. It discusses the various biochemical mediators such as nitric oxide (NO), endothelin-1 (ET-1), and the renin-angiotensin-aldosterone system (RAS) that may be involved and considers possible oxygen-sensing mechanisms involved in hypoxic adaptation such as hypoxia-inducible factor-1 (HIF-1). Those who have had HAPE once run an unpredictable but significant risk of recurrence; therefore, there may be a constitutional or genetic component in its aetiology. This paper considers the possible involvement of genes that may be involved in physiological adaptation to hypoxia (e.g., angiotensin-1 [AT(1)]-converting enzyme [ACE], tyrosine hydroxylase, serotonin transporter [5-HTT], and endothelial NO synthase [eNOS] genes). As yet, no formal association has been identified between an identified genetic polymorphism and HAPE, but genetic variation provides a possible mechanism to explain interindividual variation in response to hypoxia and enhanced or reduced performance at altitude.
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PMID:The genetic basis of high-altitude pulmonary oedema. 1476 4

Surfactant has led to a significant reduction in neonatal mortality for premature infants with lung immaturity and respiratory distress. However, surfactant therapy has been shown to be effective in the treatment of a number of other neonatal respiratory disorders and the evidence for surfactant use in such circumstances is presented. Meconium aspiration is characterised by severe atelectasis, the influx of neutrophils, edema, and hyaline membranes, with decreased levels of SP-A and SP-B and the large aggregate fraction of lung surfactant, and altered surfactant surface morphology. Meconium contains cholesterol, free fatty acids and bilirubin all of which can interfere with surfactant function in a dose-dependent fashion. Providing larger amounts of surfactant can overcome some of this inhibition. Animal models of meconium aspiration treated with surfactant have improved histology, lung mechanics and gas exchange. Studies in human infants with meconium aspiration have found elevated concentrations of total protein, albumin, and membrane-derived phospholipid in lung lavage fluid, and haemorrhagic pulmonary edema. Clinical studies in such neonates have reported improved gas exchange and clinical outcomes following surfactant treatment. More recently surfactant lavage has been shown to be a potentially efficacious therapy for such infants. The inflammatory exudate containing plasma proteins and cytokines which accompanies neonatal pneumonia may inactivate surfactant. Surfactant treatment given to animals following the tracheal instillation of group B Streptococcal resulted in significantly less bacterial growth and improved lung function. Small clinical experiences have demonstrated the benefit of surfactant to infants with pneumonia/sepsis. Pulmonary haemorrhage, which some consider a complication of surfactant therapy, has also been effectively managed using surfactant instillation. The hemoglobin and red blood cell lipids may act to inhibit natural surfactant and treatment with surfactant has been shown to improve outcome for infants with pulmonary haemorrhage. Animal models of congenital diaphragmatic hernia (CDH) have hypoplastic lungs with evidence of decreased lamellar bodies in their type II pneumocytes and resultant surfactant deficiency, and respond to surfactant replacement with improved gas exchange and lung mechanics. The lungs of human infants with CDH contain less phospholipids and phosphatidylcholine per milligram of DNA than control infants. Case reports have reported a benefit of surfactant for infants with CDH. In the near-term infants with severe respiratory distress, surfactant is one of the therapies along with inhaled nitric oxide and high frequency ventilations, that have resulted in improved outcomes. Surfactant treatment may be of significant benefit in newborn infants with respiratory compromise secondary to a number of insults, and further prospective evidence of its efficacy in such disorders is needed.
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PMID:Surfactant use for neonatal lung injury: beyond respiratory distress syndrome. 1498 Feb 86

An increase in levels of elemental Ti in the blood and lung of rats with a Ti alloy implant has been demonstrated. However, the pathophysiological role of the elevated elemental Ti level in the circulation remains unclear. Rats were implanted with Ti alloy discs for 4 weeks. The levels of elemental Ti in the blood and lung were especially increased compared with other tissues. The Ti alloy implant enhanced lung injury related to endotoxin from Gram-negative bacteria (lipopolysaccharide, LPS), which was characterized by lung edema and other histological changes such as recruitment of neutrophils, interstitial edema, and alveolar hemorrhage in the lung. In the presence of endotoxin, an increase of nitrite production was shown in the plasma and bronchoalveolar lavage fluid of rats implanted with a Ti alloy. Moreover, the Ti alloy implant further enhanced the induction of inducible nitric oxide (NO) synthase (iNOS) protein expression induced by LPS in the lung. These endotoxin-related responses in the presence or absence of the Ti alloy implant could be inhibited by aminoguanidine (an iNOS inhibitor). These results provide the first experimental evidence that circulating Ti released from Ti alloy implants has an ability to affect pulmonary iNOS protein expression, and enhance the pathogenesis of acute lung injury during endotoxemia.
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PMID:Titanium implants enhance pulmonary nitric oxide production and lung injury in rats exposed to endotoxin. 1512 3

Endogenous nitric oxide (NO) is known to modulate post-ischemic inflammatory response in various organs. However, the role of nitric oxide synthase isoforms (NOS) in mediating pulmonary post-ischemic inflammatory response is poorly understood. We therefore studied post-ischemic endothelial adhesion molecule expression and leukocyte migration in endothelial NOS knockout (eNOS-KO) mice subjected to pulmonary ischemia and reperfusion in vivo. Under anesthesia and mechanical ventilation, the left pulmonary hilum in wild-type (WT) and eNOS-KO mice was clamped for 1 hour, followed by reperfusion for up to 24 hours. In WT mice, we observed a selective up-regulation of both eNOS mRNA and protein in lung tissue, while inducible NOS (iNOS) and neuronal NOS (nNOS) remained unchanged. Survival in eNOS-KO mice was reduced due to severe pulmonary edema, underlining an increased susceptibility to ischemia-reperfusion (I/R) injury. Interstitial tissue infiltration by CD18- and CD11a-positive white blood cells as well as lung tissue water content peaked at 5 hours of reperfusion and were found significantly higher than in WT mice. Enhanced leukocyte-endothelial interaction was associated with pronounced up-regulation of vascular cell adhesion molecule (VCAM) in eNOS-KO mice during post-ischemic reperfusion. We conclude that eNOS attenuates post-ischemic inflammatory injury to the lung most probably via inhibition of endothelial adhesion molecule expression.
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PMID:Up-regulation of endothelial nitric oxide synthase inhibits pulmonary leukocyte migration following lung ischemia-reperfusion in mice. 1516 56

Pulmonary edema (PE) may occur with enterovirus 71 (EV71) infection. We monitored arterial pressure (AP) and heart rate (HR) in patients with EV71 infection and analyzed the variability of AP and HR. Sympathetic activity, AP, and HR increased with respiratory stress. Thereafter, parasympathetic activity increased with decreases in AP and HR. The lungs showed edema with inducible nitric oxide synthase (iNOS) expression. Destruction of the medial, ventral, and caudal medulla may lead to sympathetic overactivation, causing blood to shift to the lungs. The pathogenesis of PE may also involve iNOS and nitric oxide.
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PMID:Mechanism of fulminant pulmonary edema caused by enterovirus 71. 1522 28


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