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)

Rats were exposed under static conditions to phosgene at concentrations within the LCt50 range and above. Lungs were removed at various postexposure intervals. Degrees of pulmonary edema were estimated by increases in percentage of water in the lungs of exposed groups as opposed to control animals. Lungs were fractionated into four major subcellular organelle fractions: nuclear debris, mitochondrial-lysosomal, microsomal, and soluble (cytoplasmic). Activities of p-nitrophenyl phosphatase, cytochrome C oxidase, ATP'ase, and LDH within these fractions were decreased after phosgene exposure. There was a concomitant increase in serum LDH levels. One possible mechanism that may play a role in phosgene damage can be associated with either inhibition or loss of enzyme activities from the lung.
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PMID:Effect of phosgene on rat lungs after single high-level exposure. 20 Dec 20

Changes in intracellular water content appear to be common abnormalities induced by a wide variety of pathogenic mechanisms. Such changes in cell water produce changes in the water in various subcellular organelles bound by semipermeable membranes. Cell and subcell functions then alter in their turn. In isolated alveolar macrophages (rabbit), intracellular and intramitochondrial oedema reduces mitochondrial O2 utilization. Metabolic control is maintained because lactate production reverses (Pasteur effect). On reconstitution, O2 utilization and lactate production return towards normal, indicating reversibility. Cellular and intramitochondrial dehydration also reduces mitochondrial O2 utilization but metabolic control is lost because lactate production also decreases. Osmotic reconstitution does not reverse the abnormality. Exposure to hypotonic media leads to release of lysosomal enzymes (beta-glucuronidase, EC 3.2.1.31) to the extracellular phase of isolated alveolar macrophages. Some of this release is caused by exocytosis although, at low osmotic concentrations, intralysosomal oedema ultimately ruptures lysosomes, with extensive discharge of enzyme. In turn, lysosomal enzymes may injure more normal cells. Impairment of energy metabolism caused by hypoxia leads to intracellular oedema, because Na+ accumulates in the cells when ATP is no longer available for the sodium pump. Continued studies of the disorders in cell physiology caused by changes in cell and subcell water should provide important new insights into a wide variety of disease states (including pulmonary oedema).
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PMID:Intracellular and subcellular oedema and dehydration. 104 40

Adenosine is a possible mediator of myocardial and skeletal muscle blood flow regulation. Whether adenosine plays a similar role in modulating the pulmonary pressor response to acute alveolar hypoxia is not known. Adenosine levels (nmol/g tissue) in lung in six dogs ventilated with 95% N2, and 5% CO2 for a period of 3 min increased nearly 10-fold. Inosine and hypoxanthine, adenosine enzymatic degradation products, sustained a 10- and 7-fold increase, respectively. These degradative products are mainly formed in the capillary endothelial cells that contain the degradative enzyme nucleoside phosphorylase as demonstrated by histochemical techniques. To determine the effect of ATP, ADP, AMP, and adenosine on the pulmonary circulation, the in situ left lower lobe of 10 dogs was perfused at either free flow or constant flow via its pulmonary artery. ATP and ADP increased lobar vascular resistance; AMP and adenosine decreased the resistance. During hypoxic ventilation, adenosine infusions (100 nmol/ml blood) entirely abolished the increase in vascular resistance that was due solely to hypoxia. Dipyridamole produced similar responses. These data indicate that adenosine is a pulmonary vasodilator and that it may modulate the pulmonary pressor response to acute alveolar hypoxia. The findings suggest that the use of adenosine or dipyridamole may be beneficial in patients with pathologic elevations of the pulmonary vascular resistance which are a result of an exaggerated pulmonary pressor response to hypoxia, as seen in high-altitude pulmonary edema or that following cerebral injury.
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PMID:Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation. 121 95

The Fischer rat is known for its susceptibility to develop liver necrosis when challenged with paraquat (Smith et al., J. Pharmacol. Exp. Ther. 235: 172-177, 1985). We postulated that other organs, specifically the lung, may also be more susceptible to injury and examined whether lungs from Fischer (F) rats were injured more easily when challenged with active oxygen species than Sprague-Dawley (SD) rat lungs. We aimed to investigate whether increased susceptibility to oxidant injury was related to differences in lung antioxidant defenses. Perfused lungs from both rat strains were challenged by addition of H2O2 to the perfusate or by short-term hyperoxic ventilation. To assess nonoxidant modes of lung injury, we examined lung responses after exposure to protamine sulfate or neutrophil elastase. Intravascular H2O2 or 3 h in vitro hyperoxia caused lung edema in F but not SD rats, and elastase injured F rat lungs more than the lungs from SD rats. Protamine, however, injured the lungs from both strains to a similar degree. Catalase, but not superoxide dismutase or allopurinol, protected F rat lungs against edema, resulting from 3 h in vitro hyperoxia. The lung homogenate levels for reduced glutathione or conjugated dienes and the activities of lung tissue catalase, glutathione peroxidase, and cytochrome P-450 were not different between the two strains. Lung tissue ATP levels, however, were lower in F than in SD rats. Although the F rat strain appears to have an altered oxidant-antioxidant defense balance, the exact cause of the greater susceptibility to oxidant stress of the F rat strain remains elusive.
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PMID:Lung injury in Fischer but not Sprague-Dawley rats after short-term hyperoxia. 226 Jun 76

In experimental anthrax intoxication, a highly important stage of its pathogenesis consists in microcirculatory disturbances with the phenomena of blood sludge, accompanied by the increased permeability of blood vessels not only for plasma, but also for red blood cells. These disturbances result in perivascular hemorrhages, hemorrhagic infiltrations, edema and cavitary transudates. Pulmonary edema and, as a consequence, the accumulation of fluid in pulmonary alveoli and the respiratory tract are of particular importance and, probably, can be considered the basic cause of the ensuing acute and fatal asphyxia. Such vascular and pulmonary insufficiency is accompanied by a decrease in the content of macroergic compounds (and in particular ATP), the characteristic deformation of red blood cells and disturbances in their oxygen transport function, which is linked with the decreased content of 2,3-diphosphoglycerate.
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PMID:[Experimental characteristics of anthrax intoxication]. 244 50

Alpha-toxin, the major cytolysin of Staphylococcus aureus, preferentially attacks human platelets and cultured monocytes, thereby promoting coagulation and the release of interleukin-1 and tumor necrosis factor. Titers of naturally occurring antibodies in human blood are not high enough to substantially inhibit these pathological reactions. In the present study, F(ab')2 fragment preparations from hyperimmune globulin obtained from immunized volunteers were tested for their capacity to inhibit the cytotoxic action of alpha-toxin in vitro and in vivo. These antibody preparations exhibited neutralizing anti-alpha-toxin titers of 80 to 120 IU/ml, whereas titers in commercial immunoglobulin preparations were 1 to 4 IU/ml. In vitro, the presence of 2 to 4 mg of hyperimmune globulin per ml protected human platelets against the action of 1 to 2 micrograms of alpha-toxin per ml. Similarly, these antibodies fully protected human monocytes against the ATP-depleting and cytokine-liberating effects of 0.1 to 1 microgram of alpha-toxin per ml. Intravenous application of 0.5 mg (85 to 120 micrograms/kg of body weight) of alpha-toxin in cynomolgus monkeys elicited acute pathophysiological reactions which were heralded by a selective drop in blood platelet counts. Toxin doses of 1 to 2 mg (170 to 425 micrograms/kg) had a rapid lethal effect, the animals presenting with signs of cardiovascular collapse and pulmonary edema. Prior intravenous application of 4 ml of hyperimmune globulins per kg inhibited the systemic toxic and lethal effects of 1 mg (200 micrograms/kg) of alpha-toxin. In contrast, normal human immunoglobulins exhibited no substantial protective efficacy in vitro and only marginal effects in vivo. It is concluded that high-titered anti-alpha-toxin antibodies effectively protect against the cytotoxic actions of alpha-toxin.
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PMID:Human hyperimmune globulin protects against the cytotoxic action of staphylococcal alpha-toxin in vitro and in vivo. 277 80

To investigate how mitochondrial function was affected in leukotoxin (Lx)-,9,10-epoxy-12-octadecenoate-induced lung injury, lung mitochondria were extracted from isolated perfused rat lung with or without Lx-induced edematous injury. In the lung treated with 30 mumol of Lx, the mitochondrial respiration rate in states 3 and 4 significantly decreased (without mitochondrial uncoupling) concomitantly with increased release of lactate dehydrogenase (LDH), a parameter for cellular damage, into the perfusate and decreased ATP content in the lung tissue compared with those of untreated lung. Moreover, 30 mumol of Lx resulted in significant inhibition of cytochrome-c oxidase activity (vs. vehicle control). In contrast, lower doses of Lx (10 mumol) caused lung edema and cellular damage without evidence for mitochondrial dysfunction. We also examined cellular and mitochondrial damage in hydrostatic lung edema. Such edema showed neither suppressed mitochondrial respiration nor elevated LDH activity in perfusate, although lung wet weight increased as much as it did after 30 mumol Lx treatment. Our results suggest that the ex vivo mitochondrial dysfunction is one of the secondary (vs. initial augmented permeability) but specific manifestations of toxicity of Lx, and together with the previous reports, the ex vivo damaging effect of Lx against mitochondria may be ascribed not to its direct action on mitochondria but to Lx-derived cellular mechanism(s).
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PMID:Leukotoxin, 9,10-epoxy-12-octadecenoate inhibits mitochondrial respiration of isolated perfused rat lung. 757 65

Ascent to high altitude (HA) causes an increase in erythrocyte 2,3-diphsophoglycerate (DPG) and standard PO2 at 50% O2 saturation, PCO2 40 Torr, and blood pH 7.4 (P50,st). We studied the early phase of acclimatization to HA of mountaineers without and with a history of HA pulmonary edema. Tests were performed before ascent and after arrival at HA (4,559 m), approximately 22 h after the departure from low altitude (HA1) and on the following 3 days at HA (HA2-HA4). We investigated the relation between changes in DPG and P50,st, since at moderate altitude P50,st increases more rapidly than DPG, indicating that other factors may contribute to the change in P50,st. Combined effects of interaction between allosteric effectors of hemoglobin (Hb) (DPG, ATP, Cl) and Mg, which competes with Hb for DPG and ATP binding, might explain that phenomenon. Therefore concentrations of liganded Hb species were calculated from the total erythrocyte concentrations of the ligands by use of published binding constants and were related to changes in Hb-O2 affinity. P50,st increased at HA by approximately 4.5 Torr; the concentration of total DPG and ATP increased by 28 and 19%, respectively. Whereas P50,st reached a plateau already at HA1, the concentration of DPG reached its highest value at HA4. The erythrocyte Cl concentration decreased, whereas cellular Hb and Mg concentrations increased slightly. The sum of concentrations of all liganded Hb species increased, reaching 79% of its total change within 22 h after ascent; this can mainly be attributed to the change in the concentration of Hb[DPG] (+77% of total increase).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions between Hb, Mg, DPG, ATP, and Cl determine the change in Hb-O2 affinity at high altitude. 844 20

We studied whether endothelin-1 (ET-1) and leukotoxin (Lx), which have a different effects on vascular tone in isolated perfused rat lungs, also have different effects on mitochondrial function in edematous lung injury. Lung mitochondria were extracted from isolated perfused rat lungs exposed to each mediator. In lungs exposed to 0.5 nmol of ET-1, lung wet weight increased with a markedly elevated perfusion pressure but with no increase in the release of lactate dehydrogenase (LDH), an index of cell damage, into the perfusate. Neither mitochondrial respiration rate no ATP content in the lung tissue differed from those of untreated lungs. In contrast, in lungs treated with 30 mumol of Lx, lung wet weight markedly increased despite a small elevation of perfusion pressure; release of LDH into the perfusate increased, and the mitochondrial respiration rate in state 3 adn 4 significantly decreased while the ATP content in the lung tissue was less than in untreated lungs. We also examined cellular and mitochondrial damage in hydrostatic lung edema caused by raising an outflow reservoir. Mitochondrial respiration was not suppressed, and perfusate LDH activity was not increased, although lung wet weight increased as much as it did after the treatment described above. These results indicate that lung mitochondrial function is differentially affected by ET-1 and Lx, and they suggest that abnormalities in energy production by lung mitochondria are related to permeability edema.
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PMID:[Mitochondrial dysfunction in acute lung injury caused by endothelial-1 and leukotoxin]. 896 92

A reduced cation reabsorption across the alveolar epithelium decreases water reabsorption from the alveoli and could diminish clearing accumulated fluid. To test whether hypoxia restricts cation transport in alveolar epithelial cells, cation uptake was measured in rat lung alveolar type II pneumocytes (AII cells) in primary culture and in A549 cells exposed to normoxia and hypoxia. In AII and A549 cells, hypoxia caused a PO2-dependent inhibition of the Na-K pump, of Na-K-2Cl cotransport, and of total and amiloride-sensitive 22Na uptake. Nifedipine failed to prevent hypoxia-induced transport inhibition in both cell types. In A549 cells, the inhibition of the Na-K pump and Na-K-2Cl cotransport occurred within approximately 30 min of hypoxia, was stable >20 h, and was reversed by 2 h of reoxygenation. There was also a reduction in cell membrane-associated Na-K-ATPase and a decrease in Na-K-2Cl cotransport flux after full activation with calyculin A, indicating a decreased transport capacity. [14C]serine incorporation into cell proteins was reduced in hypoxic A549 cells, but inhibition of protein synthesis with cycloheximide did not reduce ion transport. In AII and A549 cells, ATP levels decreased slightly, and ADP and the ATP-to-ADP ratio were unchanged after 4 h of hypoxia. In A549 cells, lactate, intracellular Na, and intracellular K were unchanged. These results indicate that hypoxia inhibits apical Na entry pathways and the basolateral Na-K pump in A549 cells and rat AII pneumocytes in culture, indicating a hypoxia-induced reduction of transepithelial Na transport and water reabsorption by alveolar epithelium. If similar changes occur in vivo, the impaired cation transport across alveolar epithelial cells might contribute to the formation of hypoxic pulmonary edema.
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PMID:Impairment of cation transport in A549 cells and rat alveolar epithelial cells by hypoxia. 935 55


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