Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Massive elevations of serum phospholipase A2 activity have been documented in patients with septic shock. Serum PLA2 activity correlated to the degree and duration of circulatory collapse, while purified native PLA2 reproduced hypotension in experimental animals. In a prospective study of patients with septic shock, we have determined the relationship of PLA2 enzyme activity to PLA2 immunoreactivity using radiolabelled E. coli phospholipid substrate and an ELISA specific for group II human nonpancreatic PLA2. In all patients, there was a clear concordance of the two assays. Maximal PLA2 concentration was increased a mean of 554-fold over normal levels. We found no evidence to support the presence of activating or inhibitory proteins. These data confirm that the observed increase in serum PLA2 activity in septic shock is due to intravascular release of group II nonpancreatic PLA2.
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PMID:Serum phospholipase A2 enzyme activity and immunoreactivity in a prospective analysis of patients with septic shock. 174 Sep 64

To evaluate the organ specificity of pancreatic phospholipase A2 (PLA2) and the diagnostic value of the elevation of serum PLA2 levels in patients with serious diseases not involving the pancreas, we studied the organ distribution of PLA2 in autopsy specimens and serum level of PLA2 in patients who required admission to an intensive care unit (ICU). PLA2 was measured by a specific radioimmunoassay (RIA), using monoclonal antibody against human pancreatic PLA2. Organ distribution of PLA2 revealed that the pancreas showed a much higher content of pancreatic PLA2 immunoreactivity than any other organ. An abnormally high value of serum PLA2 was observed in 18 of 30 patients (60%) at ICU. Both serum PLA2 and pancreatic isoamylase were elevated in 11 patients (37%). Of 11 patients with hyperphospholipasemia and hyperamylasemia, serum creatinine was elevated in five patients and blood urea nitrogen in nine patients. Serum PLA2 levels did not always rise comparably to serum creatinine and blood urea nitrogen levels. Serum PLA2 values showed the best correlation with serum lactate dehydrogenase levels among routine blood-chemistry tests. The elevation of serum PLA2 was ascribable to renal dysfunction or ischemic pancreatic damage secondary to circulatory collapse with multiple organ failure.
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PMID:Elevation of serum phospholipase A2 in patients at an intensive care unit. 178 39

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of cardiovascular collapse in septic shock. Proximal mediators of endotoxemia, including tumor necrosis factor and interleukin 1, induce PLA2 synthesis and release, but the factors regulating PLA2 elimination are unknown. Similarly, the kinetics of PLA2 clearance during recovery from septic shock have not been examined. An autoregressive mathematical model was developed to describe the rate of PLA2 clearance during the recovery phase of septic shock. This model (which estimates that the current day's PLA2 level is 77% of the previous day's level), accounted for 89% of the variability seen in the data. The estimated circulating half-life of soluble PLA2 in septic shock in man was 32 hours. Since elevation in serum PLA2 activity is closely associated with bacteremia or endotoxemia, a significant deviation from predicted PLA2 values may denote impending relapse.
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PMID:A predictive model for the clearance of soluble phospholipase A2 during septic shock. 194 May 88

Lipocortins, a group of corticosteroid-induced phospholipase-inhibitory proteins, are thought to play a prominent role in the mediation of the anti-inflammatory effects of steroids. The synthesis and release of these proteins may represent a major endogenous mechanism of regulation of extracellular phospholipase A2 (PLA2) activity. Because soluble PLA2 activity has been associated with circulatory collapse in hyperphospholipasemic conditions, such as septic shock and pancreatitis, we examined the relationship between circulating PLA2 activity and adrenocortical function. In a prospective study of 10 episodes of septic shock, serum PLA2 and cortisol levels correlated significantly in all survivors (p less than 0.0001), whereas such a correlation was absent in all nonsurvivors (p less than 0.07). No significant correlation of cortisol and adrenocorticotropic hormone (ACTH), or PLA2 and ACTH, was found in any patient, suggesting that the stimulus for cortisol release arises from outside the hypothalamic-pituitary axis. These data suggest that, in human beings, the regulation of soluble PLA2 activity may be mediated by adrenocortical hormones, perhaps through the intermediary action of lipocortins.
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PMID:Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study. 283 77

The rate of collapse of a proton gradient across the apical membrane of rat kidney proximal tubule increases upon treatment with calcium, mercuric chloride and mellitin, substances which activate phospholipase A2. Treatment with phospholipase A2 or oleic acid also enhances the rate of proton gradient dissipation. Membrane water permeability is not affected. This phenomenon may have implications in pathological states arising from ischemia or toxic exposure.
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PMID:Phospholipase activation, free fatty acids and the proton permeability of a biological membrane. 283 61

Tumour necrosis factor (TNF) is an important mediator of endotoxin-induced vascular collapse and other inflammatory reactions. Eicosanoids have been implicated in the pathogeensis of these responses. In order to explore further the potential interactions between TNF and eicosanoid metabolism in eliciting vascular responses, we studied the effects of TNF on the bovine endothelial cell line CPAE. TNF induced cellular retraction observed by light microscope. This morphological change was monitored by the passage of iodinated protein A between adjacent cells and by release of [3H]arachidonic acid metabolites from cells. Both the morphological and functional responses were abrogated by inhibition of eicosanoid synthesis with BW755c. The release of [3H]arachidonic acid metabolites appeared to be mediated by a transient increase in phospholipase A2 activity. Phospholipase C activity was not affected by TNF. The maximal increase in phospholipase A2 activity occurred at 5 min following the addition of TNF. Phospholipase A2 activation, [3H]arachidonic acid-metabolite synthesis and passage of iodinated protein A, required both RNA and protein synthesis and were associated with an increase in the synthesis of a recently described phospholipase A2-activating protein. The Bordetella pertussis toxin, islet-activating protein, also inhibited the increase in phospholipase A2 activity, the release of [3H]arachidonic acid metabolites and the passage of iodinated protein A, suggesting that the TNF receptor-ligand interaction resulting in cellular retraction, phospholipase A2 activation and eicosanoid synthesis, is coupled through the Ni guanine nucleotide regulatory protein in these cells.
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PMID:Tumour necrosis factor (cachectin) induces phospholipase A2 activity and synthesis of a phospholipase A2-activating protein in endothelial cells. 312 74

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of circulatory collapse in experimental endotoxic shock. To assess the role of serum PLA2 in septic shock in man, we determined serum PLA2 profiles in a prospective study in 12 patients with septic shock. During the hypotensive phase of sepsis, serum PLA2 levels were consistently elevated as high as 33,428 U/ml (normal range 115 +/- 12 [SE]; n = 101). In all 12 patients, PLA2 levels correlated directly with the magnitude and duration of circulatory collapse (p less than .001), with a progressive fall of serum PLA2 levels during convalescence. In contrast, serum PLA2 levels in patients with cardiogenic shock secondary to myocardial infarction remained low. In pancreatitis, PLA2 levels paralleled fluctuations of serum amylase and lipase, whereas in septic shock without pancreatic involvement, PLA2 changes were discordant with changes in pancreatic enzymes. As well, septic shock serum PLA2 failed to crossreact by radioimmunoassay with antiserum against human pancreatic PLA2. These data are consistent with an extrapancreatic source of intravascular PLA2 release during sepsis. Since endogenous serum PLA2 levels correlate directly with the magnitude of hypotension in both experimental endotoxic shock and clinical septic shock, and since parenteral administration of purified exogenous PLA2 reproduces hypotension in experimental models, we conclude that high levels of intravascular PLA2 may contribute similarly to the circulatory collapse in septic shock in man.
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PMID:Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A2 levels with circulatory collapse. 333 73

Trichloroethylene (TCE) is a common organic solvent in use as a dry cleaning agent as well as an inhalant anesthetic. Nevertheless the effects of this material on the pulmonary surfactant which prevents alveolar collapse at maximal expiration is not known. Therefore, we have examined the effect of TCE on the intra- and extracellular surfactant pools and the activity of phospholipase A2, an enzyme which controls the remodeling of phosphatidylcholine to dipalmitoylphosphatidylcholine, the primary constituent of the pulmonary surfactant. Male CD-1 mice were treated ip with 2500 or 3000 mg/kg TCE. Twenty-four hours later mice were anesthetized and the lungs lavaged. Mice were then killed, the lungs perfused and excised, and subcellular fractions including lamellar bodies prepared. Some lungs were prepared for ultrastructural examination. Phospholipase A2 was assayed in all subcellular fractions. Phospholipid was assayed in the lavage (extracellular surfactant) and the lamellar bodies (intracellular surfactant). TCE (2500 mg/kg) caused selective exfoliation of Clara cells. However, only the dose of 3000 mg/kg TCE produced a significant decrease in the intracellular surfactant phospholipid. Minimal changes occurred in the phospholipid profiles. Phospholipase A2 specific activity was significantly decreased at both dosages within the lung microsomal fraction. In addition after treatment with 3000 mg/kg TCE the enzyme activity in the lamellar body fraction was significantly increased. These data suggest that inhalation of TCE may damage the enzymes which are responsible for synthesizing the pulmonary surfactant resulting in lower amounts of surfactant being stored and available for secretion into the alveolus.
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PMID:Pulmonary toxicity of trichloroethylene: induction of changes in surfactant phospholipids and phospholipase A2 activity in the mouse lung. 339 65

Soluble phospholipase A2 has been implicated in the pathogenesis of local and systemic inflammatory reactions. Elevated levels of circulating phospholipase A2 (PLA2) correlate with the severity of circulatory collapse and pulmonary dysfunction in gram-negative septic shock. Characterization of septic shock serum PLA2 revealed a calcium-dependent enzyme with absolute 2-acyl specificity with a pH optimum of 7.5. We tested a number of therapeutic agents for their ability to inhibit PLA2 from human septic shock serum. Chloroquine, chlorpromazine, dexamethasone base, dexamethasone sodium phosphate, indomethacin, lidocaine, oleic acid, palmitic acid, promethazine, trans-retinoic acid, rutin and dl-alpha-tocopherol were all studied over the range of 10(-2) to 10(-7) M. All agents, with the sole exception of dexamethasone base, inhibited PLA2 activity at concentrations greater than 10(-3) M. PLA2 inhibition by dexamethasone sodium phosphate was factitious, due to the formation of calcium-phosphate complexes. Of the 11 agents studied, chlorpromazine was the most effective, with an IC50 of 7.5 X 10(-5) M, a membrane concentration achievable within its therapeutic range. Inhibition was non-competitive with an apparent Ki of 5 nM. Since serum PLA2 levels correlate with mortality in both experimental endotoxemia and clinical gram-negative septic shock, and chlorpromazine was previously shown to improve survival in these conditions, we postulate that its therapeutic efficacy resides at least in part in its PLA2-inhibitory activity.
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PMID:Potential therapeutic efficacy of inhibitors of human phospholipase A2 in septic shock. 382 40

The present study was designed to obtain a basic pharmacological profile of venom from the inland taipan (Oxyuranus microlepidotus). Venom (0.05-50 micrograms/ml) produced dose-dependent contractions in guinea-pig ileum, which could not be reproduced upon second administration. The cyclooxygenase inhibitor indomethacin (1 microM), a preceding anaphylactic response induced by egg albumin and inactivation of phospholipase A2 (PLA2) by incubation with 4-bromophenacyl bromide (1.8 mM) all significantly inhibited responses to venom (0.5 micrograms/ml). Venom (0.5 micrograms/ml) caused inhibition of stimulation-induced contractions in the prostatic segment of rat vas deferens which was not significantly affected by the alpha 2-adrenoceptor antagonist idazoxan (0.3 microM). Venom (10 micrograms/ml) caused time-dependent inhibition of the rat electrically stimulated phrenic nerve-diaphragm preparation, positive inotropic and chronotropic responses in rat isolated atria and relaxation in rat endothelium-denuded and -intact isolated aortae. In endothelium-intact aortae, the nitric oxide synthase inhibitor N-nitro-L-arginine (NOLA, 0.1 mM) significantly inhibited the response to venom (10 micrograms/ml). Venom (50 micrograms/kg, i.v.) caused an immediate drop in blood pressure followed by cardiovascular collapse in anaesthetised rats. Venom (10 micrograms/kg, i.v.) caused a gradual fall in blood pressure which was sometimes accompanied by a temporary cessation of respiration. A PLA2 assay detected the presence of PLA2 in the venom. These results suggest that the venom contains a component capable of causing the synthesis of arachidonic acid metabolites and a component capable of relaxing vascular smooth muscle. The inhibitory effect on the phrenic nerve-diaphragm is probably due to the previously identified neurotoxin (paradoxin).
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PMID:Some pharmacological studies of venom from the inland taipan (Oxyuranus microlepidotus). 960 83


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