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)

Decreased circulating protein C and increased circulating thrombomodulin are markers of the prothrombotic, antifibrinolytic state associated with poor outcomes in sepsis but have not been measured in patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome). We measured circulating and intra-alveolar protein C and thrombomodulin in 45 patients with ALI/ARDS from septic and nonseptic causes and correlated the levels with clinical outcomes. Plasma protein C levels were lower in ALI/ARDS compared with normal. Lower levels of protein C were associated with worse clinical outcomes, including death, fewer ventilator-free days, and more nonpulmonary organ failures, even when only patients without sepsis were analyzed. Levels of thrombomodulin in pulmonary edema fluid from ALI/ARDS patients were >10-fold higher than normal plasma and 2-fold higher than ALI/ARDS plasma. Higher edema fluid thrombomodulin levels were associated with worse clinical outcomes. The higher levels in edema fluid compared with plasma suggest local release of soluble thrombomodulin in the lung, possibly from a lung epithelial source. To determine whether lung epithelial cells can release thrombomodulin, A549 cells and primary isolates of human alveolar type II cells were exposed to H2O2 or inflammatory cytokines. Both epithelial cell types released thrombomodulin into the media. In summary, the protein C system is markedly disrupted in patients with ALI/ARDS from both septic and nonseptic causes. The protein C system may be a potential therapeutic target in patients with ALI/ARDS.
Am J Physiol Lung Cell Mol Physiol 2003 Sep
PMID:Protein C and thrombomodulin in human acute lung injury. 1275 94

We earlier showed that the ionotropic glutamate receptor agonist N-methyl D-aspartate (NMDA) induces excitotoxic pulmonary edema, and that endogenous activation of NMDA receptors (NMDAR) could mediate lung injury caused by oxidative stress. In this study, we searched for evidence of NMDAR expression in the rat lung and in the alveolar macrophage (AM) cell line NR8383, and for possible regulation of receptor expression by NMDA. The presence of mRNA for NMDAR 1 and the four known NMDAR 2 subtypes (A, B, C, and D) was examined by reverse transcriptase-polymerase chain reaction using isoform-specific primers. NMDAR 1 was expressed in all lung regions examined (peripheral, midlung, and mainstem), as well as in trachea and the AMs. Expression of NMDAR 2A and 2B subtypes was not detected, whereas NMDAR 2C was present only in peripheral and mid-lung samples. NMDAR 2D was the dominant subtype expressed in the peripheral, gas-exchange zone of lung and in alveolar macrophages, and this expression was upregulated in lungs treated with NMDA. Western blot confirmed the presence of NMDAR 1 protein in all lung regions and in AMs. These findings provide a molecular-biological basis for the excitotoxic actions of glutamate in rat lungs and airways, and raise the question of a possible physiologic role for NMDAR in lung and airway function.
Am J Respir Cell Mol Biol 2004 Feb
PMID:Ionotropic glutamate receptors in lungs and airways: molecular basis for glutamate toxicity. 1285 8

Stimulation with norepinephrine (NE) leads to pulmonary edema and pleural effusion in rats. These pulmonary fluid shifts may result from pulmonary congestion due to the hemodynamic effects of NE and/or inflammation with an increase in vascular permeability. The contribution of these two factors were investigated in the present study. Female Sprague-Dawley rats received continuous i.v. NE infusion (0.1 mg/kg/h) over time intervals between 90 min and 72 h. After heart catheterization, pleural fluid (PF) and lung tissue were obtained. In some of the animals, a bronchoalveolar lavage (BAL) was performed. Pulmonary edema and inflammation were shown histologically. We determined the expression of interleukin (IL)-6 as one of the most potent acute-phase protein mediators in serum, PF and BAL supernatant fluid (BALF) using ELISA as well as in the lung tissue using Western blotting. Total protein concentration in BALF and PF served as indicators of increased capillary permeability. Pulmonary edema and pleural effusion appeared coincidentally with an increase in total peripheral resistance (TPR) after 6 h of NE infusion. PF reached a maximum between 8 and 16 h (2.2 +/- 0.3 ml, controls < 0.5 ml) and disappeared within 48 h. Activation of IL-6 in the fluids was observed after 8 h of NE stimulation. In the lung tissue it started after 12 h and reached 330% of the control value after 48 h. Pulmonary inflammation was documented histologically. It was accompanied by increased protein concentration in BALF after 24 h of NE treatment. Hemodynamic effects of NE are the main causative factors in the initial phase of the pulmonary fluid shifts. Additionally, NE leads to an activation of cytokines such as IL-6 and to inflammation and to an increase in capillary permeability. However, inflammation and increased capillary permeability occurred later than pulmonary edema and pleural effusion. Hence, we conclude that they are secondary factors which may contribute to maintain the fluid shifts over a longer period of time.
Mol Cell Biochem 2003 Aug
PMID:Pulmonary edema and pleural effusion in norepinephrine-stimulated rats--hemodynamic or inflammatory effect? 1296 43

Sodium absorption by an amiloride-sensitive channel is the main driving force of lung liquid clearance at birth and lung edema clearance in adulthood. In this study, we tested whether tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine involved in several lung pathologies, could modulate sodium absorption in cultured alveolar epithelial cells. We found that TNF-alpha decreased the expression of the alpha-, beta-, and gamma-subunits of epithelial sodium channel (ENaC) mRNA to 36, 43, and 16% of the controls after 24-h treatment and reduced to 50% the amount of alpha-ENaC protein in these cells. There was no impact, however, on alpha(1) and beta(1) Na(+)-K(+)-ATPase mRNA expression. Amiloride-sensitive current and ouabain-sensitive Rb(+) uptake were reduced, respectively, to 28 and 39% of the controls. A strong correlation was found at different TNF-alpha concentrations between the decrease of amiloride-sensitive current and alpha-ENaC mRNA expression. All these data show that TNF-alpha, a proinflammatory cytokine present during lung infection, has a profound influence on the capacity of alveolar epithelial cells to transport sodium.
Am J Physiol Lung Cell Mol Physiol 2004 Feb
PMID:Downregulation of ENaC activity and expression by TNF-alpha in alveolar epithelial cells. 1451 22

Gender differences in the prevalence of cardiovascular disease have been observed both clinically and experimentally. These cardioprotective effects have frequently been attributed to female hormones, however, the underlying mechanisms responsible for this cardioprotection are still poorly understood. Accordingly, this study sought to determine the contribution of ovarian hormones to the prevention of adverse ventricular remodeling and congestive heart failure in chronic volume overload (i.e. aortocaval fistula in intact or ovariectomized female rats). Ovariectomized rats developed more extensive cardiac remodeling than intact females at 21 weeks post-fistula, characterized by significantly greater left ventricular (LV) hypertrophy (167 vs. 86%, respectively, p < 0.05) and a substantial increase in LV dilatation (71%, p < 0.05) relative to control. In contrast to the eccentric hypertrophy in ovariectomized females post-fistula, the hypertrophic response in the intact female hearts was essentially concentric. While neither fistula group suffered significant mortality, there was a marked increase in the lung weight of ovariectomized rats (87%, p < 0.05) consistent with the development of pulmonary edema. Overall, the extent of myocardial remodeling and decrease in LV function in the ovariectomized females was comparable to those changes reported for males with symptomatic heart failure, while intact females maintained chronic compensated ventricular function similar to that of controls. The marked ventricular dilatation and symptoms of congestive heart failure seen at 21 weeks post-fistula in the ovariectomized females clearly demonstrate the influence of circulating ovarian hormones on the pattern of myocardial remodeling resulting from a chronic volume overload.
Mol Cell Biochem 2003 Sep
PMID:Gender mediated cardiac protection from adverse ventricular remodeling is abolished by ovariectomy. 1457 9

Lung injury is a broad descriptor that can be applied to conditions ranging from mild interstitial edema without cellular injury to massive and fatal destruction of the lung. This review addresses those methods that can be readily applied to rats and mice whose small size limits the techniques that can be practically used to assess injury. The methodologies employed range from nonspecific measurement of edema formation to techniques for calculating values of specific permeability coefficient for the microvascular membrane in lung. Accumulation of pulmonary edema can be easily and quantitatively measured using gravimetric methods and indicates an imbalance in filtration forces or restrictive properties of the microvascular barrier. Lung compliance can be continuously measured, and light and electron microscopy can be used regardless of lung size to detect edema and structural damage. Increases in fluid and/or protein flux due to increased permeability must also be separated from those due to increased filtration pressure for mechanistic interpretation. Although an increase in the initial lung albumin clearance compared with controls matched for size and filtration pressure is a reliable indicator of endothelial dysfunction, calculated alterations in capillary filtration coefficient K(f,c), reflection coefficient sigma, and permeability-surface area product PS are the most accurate indicators of increased permeability. Generally, PS and K(f,c) will increase and sigma will decrease with vascular injury, but derecruitment of microvascular surface area may attenuate the affect on PS and K(f,c) without altering measurements of sigma.
Am J Physiol Lung Cell Mol Physiol 2004 Feb
PMID:Evaluation of lung injury in rats and mice. 1471 98

A significant fraction of IL-8 in lung fluids from patients with the acute lung injury (ALI) is associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 complexes), and lung fluid concentrations of these complexes correlate with development and outcome of ALI. In this study, we examined whether anti-IL-8:IL-8 complexes exhibit proinflammatory activity in vitro. These complexes were purified from pulmonary edema fluid samples obtained from patients with ALI. First, we found that IL-8 bound to the autoantibody retained its ability to trigger chemotaxis of neutrophils, whereas control antibody did not have significant chemotactic activity. Next, we examined the ability of anti-IL-8:IL-8 complexes to induce neutrophil activation, i.e., neutrophil respiratory burst and degranulation. Anti-IL-8:IL-8 complexes triggered superoxide and myeloperoxidase release from human neutrophils, and in contrast, the control antibody had no effect. We also demonstrated that IgG receptor, FcgammaRIIa, is the receptor involved in cellular activation mediated by these complexes. Blockade of FcgammaRIIa completely reverses activity of the complexes with the exception of chemotaxis. Both FcgammaRIIa and IL-8 receptors mediate chemotactic activity of anti-IL-8:IL-8 complexes, with FcgammaRIIa being, however, a predominant receptor. Furthermore, activity of the complexes is partially dependent on the activation of the mitogen-activated protein kinases, i.e., ERK and p38, important components of the FcgammaRIIa signaling cascade. Anti-IL-8:IL-8 complexes may therefore be involved in the pathogenesis of lung inflammation in clinical acute lung injury.
Am J Physiol Lung Cell Mol Physiol 2004 Jun
PMID:Proinflammatory activity of anti-IL-8 autoantibody:IL-8 complexes in alveolar edema fluid from patients with acute lung injury. 1513 92

Proteomics is the large-scale analysis of protein profiles. This approach has not yet been reported in the study of acute lung injury (ALI). This study details protein profiles in plasma and pulmonary edema fluid (EF) from 16 ALI patients and plasma and bronchoalveolar lavage fluid (BALF) from 12 normal subjects. More than 300 distinct protein spots were evident in the EF and BALF of both normal subjects and ALI patients. Of these, 158 were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In the plasma and EF protein profile of ALI patients, there were multiple qualitative changes. For instance, in all normal subjects, but in only one of the ALI patients, seven distinct surfactant protein A isoforms were evident. Nearly all ALI patients also had protein spots that indicate truncation or other posttranslational modifications. Several of these novel changes could serve as new biomarkers of lung injury.
Am J Physiol Lung Cell Mol Physiol 2004 Jun
PMID:Proteomic analysis of pulmonary edema fluid and plasma in patients with acute lung injury. 1513 92

Inadequate nutrition complicates the clinical course of critically ill patients, and many of these patients develop pulmonary edema. However, little is known about the effect of malnutrition on the mechanisms that resolve alveolar edema. Therefore, we studied the mechanisms responsible for the decrease in alveolar fluid clearance in rats exposed to malnutrition. Rats were allowed access to water, but not to food, for 120 h. Then, the left and right lungs were isolated for the measurement of lung water volume and alveolar fluid clearance, respectively. The rate of alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue dye that was instilled into the distal air spaces with an isosmolar 5% albumin solution over 1 h. Malnutrition decreased alveolar fluid clearance by 38% compared with controls. Amiloride (10(-3) M) abolished alveolar fluid clearance in malnourished rats. Either refeeding for 120 h following nutritional deprivation for 120 h or an oral supply of sodium glutamate during nutritional deprivation for 120 h restored alveolar fluid clearance to 91 and 86% of normal, respectively. Dibutyryl-cGMP, a cyclic nucleotide-gated cation channel agonist, increased alveolar fluid clearance in malnourished rats supplied with sodium glutamate. Terbutaline, a beta(2)-adrenergic agonist, increased alveolar fluid clearance in rats under all conditions (control, malnutrition, refeeding, and glutamate-treated). These results indicate that malnutrition impairs primarily amiloride-insensitive and dibutyryl-cGMP-sensitive alveolar fluid clearance, but this effect is partially reversible by refeeding, treatment with sodium glutamate, or beta-adrenergic agonist therapy.
Am J Physiol Lung Cell Mol Physiol 2004 Jun
PMID:Malnutrition impairs alveolar fluid clearance in rat lungs. 1497 28

Transport of protein across the alveolar epithelial barrier is a critical process in recovery from pulmonary edema and is also important in maintaining the alveolar milieu in the normal healthy lung. Various mechanisms have been proposed for clearing alveolar protein, including transport by the mucociliary escalator, intra-alveolar degradation, or phagocytosis by macrophages. However, the most likely processes are endocytosis across the alveolar epithelium, known as transcytosis, or paracellular diffusion through the epithelial barrier. This article focuses on protein transport studies that evaluate these two potential mechanisms in whole lung or animal preparations. When protein concentrations in the air spaces are low, e.g., albumin concentrations <0.5 g/100 ml, protein transport demonstrates saturation kinetics, temperature dependence indicating high energy requirements, and sensitivity to pharmacological agents that affect endocytosis. At higher concentrations, the protein clearance rate is proportional to protein concentration without signs of saturation, inversely related to protein size, and insensitive to endocytosis inhibition. Temperature dependence suggests a passive process. Based on these findings, alveolar albumin clearance occurs by receptor-mediated transcytosis at low protein concentrations but proceeds by passive paracellular mechanisms at higher concentrations. Because protein concentrations in pulmonary edema fluid are high, albumin concentrations of 5 g/100 ml or more, clearance of alveolar protein occurs by paracellular pathways in the setting of pulmonary edema. Transcytosis may be important in regulating the alveolar milieu under nonpathological circumstances. Alveolar degradation may become important in long-term protein clearance, clearance of insoluble proteins, or under pathological conditions such as immune reactions or acute lung injury. acute respiratory distress syndrome; endocytosis; diffusion; protein transport pulmonary edema
Am J Physiol Lung Cell Mol Physiol 2004 Apr
PMID:Mechanisms of alveolar protein clearance in the intact lung. 1500 32


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