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)

Platelet-activating factor (PAF) is an important endogenous mediator of pulmonary edema in many models of acute lung injury. PAF triggers edema formation by simultaneous activation of two independent pathways; one is mediated by a cyclooxygenase metabolite, and the other is blocked by quinine. We examined the hypothesis that the cyclooxygenase-dependent part of PAF-induced edema is mediated by prostaglandin E(2) (PGE(2)). In isolated rat lungs, PAF administration stimulated release of PGE(2) into the venous effluate and increased lung weight as a measure of edema formation. Perfusion with a neutralizing PGE(2) antibody attenuated the PAF-induced edema formation. In vivo, E-prostanoid 3-receptor-deficient mice showed less pulmonary Evans blue extravasation in response to PAF injection than did mice deficient in EP1, EP2, or EP4 receptors. Perfusion of rat lungs with PGE(2) caused pulmonary edema, which was largely prevented by inhibition of voltage-gated potassium channels (25 nM beta-dendrotoxin), but not by blocking calcium-dependent potassium currents (100 micro M paxilline). In line with its effects on PGE(2)-induced edema formation, beta-dendrotoxin attenuated PAF-induced edema partly if given alone, and completely in combination with quinine. Our findings suggest that PAF-triggered edema is partly mediated by the release of PGE(2), activation of EP3 receptors, and activation of voltage-gated potassium channels.
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PMID:Platelet-activating factor-induced pulmonary edema is partly mediated by prostaglandin E(2), E-prostanoid 3-receptors, and potassium channels. 1220 61

The effects of carbazochrome sodium sulfonate (AC-17), a capillary stabilizer, on pulmonary edema and dysfunction induced by ioxaglate, an ionic radiographic contrast medium, were evaluated in rats. The pulmonary edema was evaluated by the extravasation of intravenously injected Evans blue into lung tissues, while pulmonary dysfunction was determined by monitoring blood gasses including pO(2). Ioxaglate (4 g I/kg, i.v.) caused a marked increase in vascular permeability and a decrease in arterial pO(2). AC-17 reversed the ioxaglate-induced vascular hyperpermeability in a dose-dependent manner. In addition, AC-17 (10 mg/kg) significantly inhibited the decrease in arterial pO(2). In isolated rat pulmonary mast cells, ioxaglate markedly enhanced the histamine release, which was not affected by AC-17. On the other hand, AC-17 did significantly blocked the hyperpermeability induced in cultured bovine endothelial cells by tryptase, thrombin and proteinase-activated receptor-2 agonist peptide (SLIGKV-NH(2)). These findings suggest that AC-17 blocks radiographic contrast medium-induced pulmonary dysfunction by maintaining the endothelial barrier function. Thus, the compound is potentially useful for the prophylaxis of contrast media-induced acute pulmonary adverse events during angiography.
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PMID:Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats. 1220 59

Compelling evidence indicates that the small intestine is the primary source of factors inducing lung injury after major surgery and that the lymphatic system is the major route by which these gut-derived factors reach the pulmonary circulation. This study investigated the mechanism of lung edema induced by surgical stress. After subjecting male, fasted, pathogen-free Sprague-Dawley rats to surgical stress (laparotomy and intestinal handling for 5 min), followed by ventilation for 5 h, we measured H2O2 production in the mucosa of small intestine and in the lung using 2',7'-dichlorofluorescein and intravital fluorescence microscopy. In addition, H2O2 in mesenteric lymph was measured using a quantitative assay; lung permeability was assessed as a function of extravasation of Evans blue dye; neutrophil accumulation was visualized by intravital fluorescence microscopy and assessed as a function of myeloperoxidase activity; and TNF-alpha levels were measured using a specific ELISA. The intensity of 2',7'-dichlorofluorescein fluorescence in the mucosa of small intestine, H2O2 levels of mesenteric lymph, and lung permeability were all significantly higher in rats subjected to surgical stress than in control animals. Moreover, all of these effects were blocked by pretreatment with a specific xanthine oxidase inhibitor. Surgical stress did not increase neutrophil accumulation or TNF-alpha production in the lung. In conclusion, surgical stress induces xanthine oxidase-dependent H2O2 production in the small intestine. The H2O2 then enters the mesenteric lymph and travels to the lung, where it increases capillary permeability and thus induces edema.
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PMID:Hydrogen peroxide derived from intestine through the mesenteric lymph induces lung edema after surgical stress. 1475 90

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.
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PMID:Malnutrition impairs alveolar fluid clearance in rat lungs. 1497 28

To investigate the role of interleukin (IL)-10 gene therapy on the reperfusion-induced lung injury, we utilised the technique of liposomal gene delivery before the induction of intestinal ischemia. Plasmid DNA encoding human IL10 (hIL-10) or empy vector was injected intraperitoneally 24 h before the study. Male Balb/c mice randomized into three groups: Sham operated control (n = 12), empty plasmid vector (n = 12), and hIL-10 gene therapy group (n = 12). The ischemia was generated by selective occlusion of superior mesenteric artery for 60 min and followed by reperfusion for 30 min. Lung tissue neutrophil infiltration was determined by myeloperoxidase assay and neutrophil counts. For the determination of lung tissue microvascular permeability, Evans blue dye injection was made and the lung edema was assessed by wet/dry ratio. hIL-10 protein expression was studied by immunostaining and ELISA. We found that pre-ischemic hIL-10 overexpression attenuated dye extravasation, leukocyte sequestration and reduced pulmonary tissue injury compared to the empty vector-injected control. Our study indicates that pre-ischemic hIL-10 overexpression attenuates lung injury caused by intestinal ischemia-reperfusion.
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PMID:Interleukin-10 gene therapy attenuates pulmonary tissue injury caused by mesenteric ischemia-reperfusion in a mouse model. 1614 82

Xanthine oxidoreductase (XOR) plays a prominent role in acute lung injury because of its ability to generate reactive oxygen species. We investigated the role of XOR in ventilator-induced lung injury (VILI). Male C57BL/6J mice were assigned to spontaneous ventilation (sham) or mechanical ventilation (MV) with low (7 ml/kg) and high tidal volume (20 ml/kg) for 2 h after which lung XOR activity and expression were measured and the effect of the specific XOR inhibitor allopurinol on pulmonary vascular leakage was examined. In separate experiments, rat pulmonary microvascular endothelial cells (RPMECs) were exposed to cyclic stretch (5% and 18% elongation, 20 cycles/min) for 2 h before intracellular XOR activity measurement. Lung XOR activity was significantly increased at 2 h of MV without changes in XOR expression. There was evidence of p38 MAP kinase, ERK1/2, and ERK5 phosphorylation, but no change in JNK phosphorylation. Evans blue dye extravasation and bronchoalveolar lavage protein concentration were significantly increased in response to MV, changes that were significantly attenuated by pretreatment with allopurinol. Cyclic stretch of RPMECs also caused MAP kinase phosphorylation and a 1.7-fold increase in XOR activity, which was completely abrogated by pretreatment of the cells with specific MAP kinase inhibitors. We conclude that XOR enzymatic activity is significantly increased by mechanical stress via activation of p38 MAP kinase and ERK and plays a critical role in the pathogenesis of pulmonary edema associated with VILI.
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PMID:Mechanical stress activates xanthine oxidoreductase through MAP kinase-dependent pathways. 1663 22

Sepsis-induced acute lung injury (ALI) is characterized by injury of the pulmonary microvascular endothelial cells (PMVEC) leading to high-protein pulmonary edema. Inducible NO synthase (iNOS) mediates trans-PMVEC protein leak in septic mice in vivo and in murine PMVEC under septic conditions in vitro, but the role of iNOS in human PMVEC protein leak has not been addressed. We hypothesized that iNOS in human neutrophils, but not human PMVEC, mediates septic trans-PMVEC protein leak in vitro. We isolated human PMVEC from lung tissue using magnetic bead-bound anti-PECAM antibody and assessed Evans blue albumin leak across human PMVEC monolayers under septic conditions in the presence/absence of human neutrophils. PMVEC were used at passages 3-4, seeded on 3 mum Transwell inserts and grown to confluence. Cytomix-stimulated trans-PMVEC albumin leak was not attenuated by pre-treatment with 1400 W, a selective iNOS inhibitor, or l-NAME, a non-selective NOS inhibitor. In neutrophil-PMVEC co-culture, basal unstimulated trans-EB-albumin leak was 0.6+/-0.3%, which was increased by cytomix stimulation to 11.5+/-4.4%, p<0.01. Cytomix-stimulated EB-albumin leak in neutrophil-PMVEC co-cultures was inhibited by pre-treatment with 1400 W (3.8+/-1.0%, p<0.05) or l-NAME (4.0+/-1.1%, p<0.05). Pre-treatment of neutrophil-PMVEC co-cultures with PEG-SOD (superoxide scavenger) and FeTPPS (peroxynitrite scavenger) also significantly attenuated neutrophil-dependent cytomix-stimulated leak (4.7+/-3.0%, p<0.05; 0.5+/-1.0%, p<0.01, respectively). In conclusion, trans-human PMVEC albumin leak under septic conditions is dependent on iNOS activity specifically in neutrophils, but not in PMVEC themselves. Septic neutrophil-dependent trans-PMVEC albumin leak may be mediated by peroxynitrite.
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PMID:Inducible NO synthase (iNOS) in human neutrophils but not pulmonary microvascular endothelial cells (PMVEC) mediates septic protein leak in vitro. 1745 52

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of acute respiratory failure associated with high morbidity and mortality. Although ALI/ARDS pathogenesis is only partly understood, pulmonary endothelium plays a major role by regulating lung fluid balance and pulmonary edema formation. Consequently, endothelium-targeted therapies may have beneficial effects in ALI/ARDS. Recently, attention has been given to the therapeutic potential of purinergic agonists and antagonists for the treatment of cardiovascular and pulmonary diseases. Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface P2Y receptors. We previously described ATP-induced endothelial cell (EC) barrier enhancement via a complex cell signaling and hypothesized endothelial purinoreceptors activation to exert anti-inflammatory barrier-protective effects. To test this hypothesis, we used a murine model of ALI induced by intratracheal administration of endotoxin/lipopolysaccharide (LPS) and cultured pulmonary EC. The nonhydrolyzed ATP analog ATPgammaS (50-100 muM final blood concentration) attenuated inflammatory response with decreased accumulation of cells (48%, P < 0.01) and proteins (57%, P < 0.01) in bronchoalveolar lavage and reduced neutrophil infiltration and extravasation of Evans blue albumin dye into lung tissue. In cell culture model, ATPgammaS inhibited junctional permeability induced by LPS. These findings suggest that purinergic receptor stimulation exerts a protective role against ALI by preserving integrity of endothelial cell-cell junctions.
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PMID:Protective effect of purinergic agonist ATPgammaS against acute lung injury. 1799 88

Death after hemorrhagic shock (HS) may be caused by a generalized reperfusion injury, particularly noticeable in the gut. A period of tissue ischemia followed by reinstitution of perfusion produces severe inflammation that can be blocked in mice by preventing the binding of a pathogenic natural immunoglobulin M (IgM) of defined specificity to antigens in reperfused tissue by using a soluble peptide analogue of the IgM tissue target. We hypothesize that this agent can improve end points of rat HS: death, intestinal injury, and lung injury. Male Sprague-Dawley rats were anesthetized; 50% of calculated blood volume was removed for 120 min, shed blood, then returned; and animals were sacrificed at 72 h. One group of rats received i.v. analogue ([N2] 300 microg) with the return of shed blood. Small intestine and lung were evaluated by histological examination and immunohistochemistry. Lung edema was assessed by Evans blue extravasation and histological examination. I.v. N2 decreased experimental mortality from 62% to 12% (P < 0.05). Associated with this was diminution of gut injury score from 57.8% +/- 5.5% to 19.5% +/- 2.5% (P < 0.05), lung injury from 21.4 +/- 1.5 to 14.8 +/- 1.3 polymorphonuclear leucocytes per high-power field x400 (P < 0.05), and Evans blue extravasation index from 0.61 +/- 0.14 to 0.18 +/- 0.06 (P < 0.05). As well, the deposition of IgM and C3 that is seen in intestinal villi from HS was not present in N2-treated rats. The N2 peptide agent that blocks reperfusion injury in mice prevents death from rat HS, as well as attenuates gut reperfusion injury and its remote target injuries. These data suggest that death from HS is caused by reperfusion injury, and that an agent derived from mice is effective in rats when given in real therapeutic time.
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PMID:Attenuation of the effects of rat hemorrhagic shock with a reperfusion injury-inhibiting agent specific to mice. 1910 10

The in vivo and in vitro pharmacological effects of leptoxin, one of the most lethal protein toxins known at present date (LD(50) 0.5+/-0.03 microg/kg i.v., mice) isolated from Leptodactylus pentadactylus skin secretion, were studied. In rats, leptoxin (1.0 microg/kg, i.v.) induced cardiorespiratory collapse with abundant tracheal secretion followed by sudden death. The cardiovascular shock, pulmonary edema and mortality were not prevented by pretreating the animals with effective doses of pharmacological blockers, i.e., atropine with or without bilateral vagotomy, phentolamine, propranolol, hexamethonium, captopril, dexamethasone, indomethacin, L-NAME, promethazine, Ginkgolide BN-52021 or tezosentan. Pulmonary macroscopic examination revealed increased tracheobronchial secretion, hemorrhagic areas and edema. Microscopic examination showed intense vascular congestion, alveolar and septal interstitial hemorrhage and alveolar edema, without infiltrated inflammatory cells. Leptoxin increased pulmonary index (0.67+/-0.09 vs. 1.55+/-0.24; p<0.05) and the Evans blue concentration in the bronchoalveolar fluid (1.24+/-0.17 vs. 4.17+/-1.47 microg/microL; p<0.01) and in the lung parenchyma (40.73+/-3.27 vs. 65.33+/-4.51 microg/microL; p<0.03). Leptoxin increased the pulmonary perfusion pressure from 13.7+/-5.3 to 54.0+/-6.3 mmHg. It also induced a vasoconstrictor effect in the perfused mesenteric vascular bed that could be explained by a hyperreactivity to phenylephrine. Thus, the results suggest that leptoxin-induced death occurs by acute pulmonary edema due to increased microvascular pulmonary pressure evoked by direct vasoconstriction. Despite its strong toxicity, the role of leptoxin in L. pentadactylus skin remains unknown.
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PMID:Isolation and pharmacological effects of leptoxin, a novel proteic toxin from Leptodactylus pentadactylus skin secretion. 1950 92


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