Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paraquat is a herbicide known to cause pulmonary edema in its acute toxic phase. Many investigators showed that paraquat induces morphological changes of alveolar epithelial cells even in its early phase. Controversy still exists, however, as to whether pulmonary vascular endothelial cells are also morphologically vulnerable to paraquat. To test the direct toxicity and metabolic changes of pulmonary vascular endothelial cells after paraquat addition, porcine pulmonary artery endothelial cells (PPAEC) were cultured. Thrombin- or bradykinin-stimulated PGI2 production was enhanced significantly, and the angiotensin converting enzyme (ACE) activity of cell lysate of PPAEC was significantly suppressed after a 24-hour incubation with 10(-4) M of paraquat. No further thrombin-induced enhancement of PGI2 production was noted after a 48-hour incubation. The alterations in arachidonic acid metabolism and ACE activity mentioned above did not result from cytotoxicity of paraquat because LDH release into culture medium was not increased during 72 hours of incubation with paraquat. Longer incubation more than 48 hours, in turn, induces obvious toxic effects on PPAEC.
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PMID:[Arachidonic acid metabolism and angiotensin converting enzyme activity by cultured porcine pulmonary artery endothelial cells are affected with paraquat]. 166 45

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Poisoning in the elderly. Epidemiological, clinical and management considerations. 179 7

It is well known that pulmonary influx of neutrophils is involved in lung injury in patients with adult respiratory distress syndrome (ARDS). Neutrophils are major contributors to the self-defence mechanism, however, adverse effects of neutrophils have also been recognized. Recently, we found that a highly toxic substance, 9, 10-epoxy-12-octadecenoate (leukotoxin) is biosynthesized by human neutrophils. This study was designed to investigate whether or not leukotoxin participates in lung injury in ARDS and coagulation abnormality which is often associated with ARDS. Intravenous injection of leukotoxin (100 mumol/kg) caused acute edematous lung injury, which was evidenced by increased lung weight, albumin concentrations, and angiotensin converting enzyme activities in lung lavages. Pulmonary capillary endothelial damage and pulmonary edema were observed by electron microscopy. Moreover, considerable amounts of leukotoxin were detected in lung lavage fluid of rats exposed to pure oxygen for 60 h and patients with ARDS. An increased number of neutrophils and albumin concentrations were also observed in these lavage fluids. Intravenous injection of leukotoxin (100 mumol/kg) induced coagulation abnormalities such as disseminated intravascular coagulation. Increased levels of plasma leukotoxin were detected in ARDS patients with coagulation abnormalities. These results suggest that leukotoxin biosynthesized by neutrophils is an important contributor to lung injury in ARDS and associated coagulation abnormalities.
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PMID:[ARDS and leukotoxin]. 185 3

In order to elucidate the role of arachidonic acid in the pathogenesis of ozone-induced pulmonary edema, isolated rat lungs were exposed to 14C-arachidonic acid in the presence or absence of ozone and the incorporation of radiolabelled arachidonate into pulmonary cell lipids was studied. The perfusates from these studies were also subjected to differential extraction and thin layer chromatography (t.l.c.) to determine synthesis of both cyclo-oxygenase and lipoxygenase products. In the presence of an edemagenic concentration of ozone, isolated lungs incorporated significantly less exogenous arachidonic acid into phosphatidyl choline and phosphatidyl ethanolamine, whereas incorporation into phosphatidyl inositol or serine was not affected. The edemagenic concentration of ozone also increased production of a variety of arachidonic acid metabolites via cyclo-oxygenase and lipoxygenase pathways. In separate studies, a similar ozone exposure did not affect 14CO2 production, resulting from the metabolism of 14C-antipyrine by mixed function oxidases (MFO). Similarly, an edemagenic concentration of ozone did not affect pulmonary angiotensin converting enzyme activity (ACE) as determined by the rate of formation of 14C-hippuric acid from 14C-hippuryl-histidyl-leucine (14C-HHL). Thus, acute ozone exposure is specifically associated with a reduced incorporation of arachidonate into phospholipids and with an increased conversion of arachidonate into bio-active metabolites.
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PMID:A study of ozone-induced edema in the isolated rat lung in relation to arachidonic acid metabolism, mixed-function oxidases and angiotensin converting enzyme activities. 196 4

In rabbits intravenous administration of antibodies to lung angiotensin converting enzyme (ACE) results in a rapid redistribution of ACE on the plasma membrane of pulmonary endothelium with fixation of complement and development of fatal pulmonary edema. In survivors given daily injections of antibodies, ACE disappears from the lung ("antigenic modulation") and the rabbits become resistant to further immune injury. To test the hypothesis that these events depend on a functionally intact mechanism of cell activation, rabbits received, in addition to anti-ACE antibodies, chlorpromazine, a drug that inhibits calmodulin and protein kinase C and decreases plasma membrane fluidity. Initially, chlorpromazine inhibited antigen redistribution, fixation of complement, and development of pulmonary edema. In rabbits maintained on chlorpromazine and receiving daily anti-ACE antibodies this effect became attenuated and the rabbits eventually developed ACE redistribution, complement fixation, and pulmonary edema. We conclude that chlorpromazine temporarily inhibits antigenic modulation in vivo, presumably through its action on calcium-mediated antibody-cell surface antigen interaction.
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PMID:Lung injury mediated by antibodies to endothelium. III. Effect of chlorpromazine in rabbits. 217 23

In spite of the development of various antibiotics, management of elderly patients with pneumonia remains an important problem. It is suggested that adult respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) often occur in elderly patients with pneumonia. Although neutrophils are suggested to be involved in the genesis of these conditions, details remain unknown. We demonstrated that a highly cytotoxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized from linoleate by human neutrophils, thus it was named leukotoxin. Leukotoxin was detected in lung lavages from patients with ARDS. In these lung lavages, increases in albumin concentration and angiotensin converting enzyme (ACE) activity were also observed. Similar results were observed in lung lavages from rats after exposure to hyperoxia for 60 hours in an experimental model of ARDS. Intravenous administration of leukotoxin (100 mumol/kg) caused lung edema. Albumin concentration and ACE activity were increased in lung lavages of rats receiving leukotoxin. In contrast, these changes were not observed in rats administered with linoleate. Furthermore, administration of leukotoxin (100 mumol/kg) caused coagulation abnormality, i.e., increase in fibrin-fibrinogen degradation products, decrease in fibrinogen, and prolongation of activated partial thromboplastin time and prothrombin time. Administration of linoleate did not induce these changes. It is indicated that O2- was produced by respiratory burst enzyme located in neutrophil plasma membrane, and that hydroxyl radicals derived from O2- by Fenton reaction were responsible for leukotoxin synthesis. From our results, leukotoxin, a product of hydroxyl radicals and linoleate, might be responsible for the genesis of ARDS and DIC.
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PMID:[Leukotoxin and pulmonary injury]. 238 90

In this experimental study, we investigated pathophysiology of respiratory failure with acute pancreatitis. Pancreatitis was induced by injection of 15% Na-taurocholate 1 ml/kg into the main pancreatic duct of the dogs. Experimental dogs were divided into two groups based on the value of Respiratory Index (R-Index). Group A included 9 dogs in whom respiratory failure was not recognized (R-Index less than 0.5) and Group B included 9 dogs with respiratory failure (R-Index less than 0.5). All the dogs were sacrificed 12 hours after induction of pancreatitis, and histological findings were examined. Quantity of water in the lung (Qwl) was also measured by gravimetric method. Group B showed severe hypoxia with hypocapnia, and increase of A-aDO2, R-Index, and decrease of a/A PO2. Qwl in Group B increased significantly comparing with Group A. In biochemical study, increase of serum lipase, triglyceride, free fatty acid, and angiotensin converting enzyme were observed in Group B. These results indicate that respiratory failure with acute pancreatitis is due to lung edema following injury of the capillary of the lung. The role of free fatty acid liberated by lipolysis was suggested in the mechanism of pulmonary damage with acute pancreatitis.
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PMID:[Experimental study of respiratory failure with acute pancreatitis in dogs]. 241

Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Lung hydroxyproline content was measured as an index of interstitial fibrosis. Cardiac right ventricular hypertrophy was determined by the right ventricle to the left ventricle plus septum weight ratio (RV/LV + S). Rats receiving SC39026 alone did not differ significantly from untreated control animals with respect to any of the quantitative endpoints, although rarefaction of Type I pneumocytes was observed in the electron micrographs of these animals. Monocrotaline-treated rats, in contrast, developed a significant increase in RV/LV + S, and exhibited pulmonary edema, inflammation, fibrosis, and muscularization and occlusive mural thickening of the pulmonary small arteries and arterioles. These monocrotaline-induced structural changes were accompanied by decreased lung ACE and PLA activities, and increased PGI2 and TXA2 production, and by an increase in lung hydroxyproline content. Cotreatment with SC39026 ameliorated the monocrotaline-induced pulmonary vascular wall thickening and the cardiac right ventricular hypertrophy. These data suggest that inappropriate neutrophil elastase activity contributes to monocrotaline pulmonary vasculopathy and hypertension. On the other hand, cotreatment with SC39026 had no significant effect on the severity of the monocrotaline-induced lung inflammatory reaction, the pulmonary endothelial dysfunction, or the increase in lung hydroxyproline content.
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PMID:Monocrotaline-induced cardiopulmonary injury in rats. Modification by the neutrophil elastase inhibitor SC39026. 254 80

Lung endothelial cell injury may be an important early event in the pathogenesis of increased permeability pulmonary edema. Since angiotensin converting enzyme (ACE) is located on the luminal surface of the endothelial cell membrane, we sought to determine whether the conversion of angiotensin I (AI) to angiotensin II is decreased after acute lung injury to rats, induced by alpha-naphthylthiourea (ANTU), and we investigated the mechanism of the decrease. We found that lungs isolated from rats treated 4 h earlier with ANTU at a dose of 15 mg/kg body weight (BW) had decreased AI conversion when perfused with Krebs-Henseleit at a constant flow rate of 30 ml/min/kg BW. When perfusate flow rate was increased from 30 to 50 ml/min/kg BW, lungs isolated from rats treated with 10 mg/kg BW ANTU also had decreased AI conversion when compared to controls treated with a vehicle, Tween 80. Investigating the mechanism of decreased AI conversion, there were no differences among experimental groups in pulmonary arterial pressures or effluent perfusate pH or pO2. There was no correlation between lung wet/dry weight ratios and the extent of AI conversion among control rat lungs. Lung homogenate and serum ACE activity did not differ among control rats and rats pretreated with the two doses of ANTU. Ultrastructural studies revealed an increased percentage of capillaries with blebbing of endothelial cells in lungs injured with ANTU, as compared to controls, but no evidence of increased endothelial cell denudation in injured lungs. We conclude that angiotensin I conversion is decreased after ANTU lung injury and that the extent of decrease is related to the dose of ANTU and to perfusate flow rate. Although we cannot exclude decreased vascular surface area perfused as a cause of decreased conversion, we speculate that subtle changes in the luminal endothelial cell membrane may have caused decreased AI conversion after ANTU lung injury.
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PMID:Studies on the mechanism of decreased angiotensin I conversion in rat lungs injured with alpha-naphthylthiourea. 299 22

The effects of ANTU-induced acute pulmonary capillary injury on lung and serum ACE functional activity and the specific accumulation of radio-labelled anti-ACE in lung were explored. Rats were injected either with ANTU or the solvent and sacrificed at various intervals up to one week after injection. All ANTU-injected animals developed pulmonary edema and bilateral pleural effusions which resolved by the one week time point. At no time was there any significant change in serum ACE levels. The specific activity of total lung ACE however rose from 11.0 +/- .95 (mean +/- SEM) to 18.4 +/- 1.1 by two hours after ANTU; by 24 hours, however, solubilized lung ACE had fallen significantly to 6.9 +/- .79 (p less than .01). Total lung ACE had returned to control values by one week. In parallel groups of animals the accumulation of 125I-labelled anti-ACE (AA) or normal sheep immunoglobulin (NSG) was compared in control and ANTU-treated rats. The ratio of the radioactivity in the lungs of AA--injected animals to that in NSG--injected animals fell significantly after ANTU administration (5.0 +/- .88 to 1.2 +/- .28 at 2 hours) suggesting that immunoreactive ACE had fallen despite an increase in ACE functional activity. The decreased binding of AA at the early time points perhaps reflects internalization of endothelial cell ACE in response to injury and an inability of the antibody to interact with the enzyme. The reduction in binding at 24 hours (1.38 +/- .47) correlates with a reduction in total lung ACE. ANTI-ACE may be a useful reagent for quantitating endothelial cell damage following lung injury.
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PMID:The effect of alphanapthylthiourea (ANTU)-induced acute injury on lung binding of antibody to angiotensin converting enzyme (ACE). 302 70


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