Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476273 (respiratory distress)
 19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Premature infants who have self-limited respiratory distress syndrome (RDS) rapidly improve, whereas infants with a complicated respiratory course are more likely to develop bronchopulmonary dysplasia (BPD), a chronic lung disorder that is the result of prolonged lung injury and impaired healing. The balance of competing activities of coagulation and fibrinolysis may contribute to the premature lung's response to acute injury and determine, in part, whether there is early resolution or protracted alveolar inflammation. To determine the relative activities of the coagulation and fibrinolytic pathways in neonatal lung injury, procoagulant (PC) and plasminogen activator (PA) activities were measured in undiluted cell-free lung lavage samples obtained serially over the first 28 days of life from 11 infants with self-limited RDS, 11 infants with evolving BPD, and 5 mechanically ventilated control infants without lung disease. Lung lavage from all three groups contained readily detectable procoagulant activity due mainly to the tissue factor-Factor VII complex. Plasminogen activator activity was relatively high in control lavage samples but depressed on the first day of life in the two groups of infants with lung disease: median, 0.3814 IU/ml (control); 0.0541 IU/ml (RDS); and 0.0454 IU/ml (BPD), p < 0.05 in each case compared with control. Two infants with severe lung disease had no detectable plasminogen activator activity in lung lavage on the first day of life. Depressed fibrinolytic activity correlated with severity of lung disease assessed radiographically and by pulmonary function measurements. Plasminogen activator activity was due to both tissue plasminogen activator and urokinase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disordered pathways of fibrin turnover in lung lavage of premature infants with respiratory distress syndrome. 148 46

Two ELISA methods using monoclonal antibodies, are described for the measurement of tPA:Ag and tPA-PAI-1 complexes. On normal population tPA:Ag was found with a mean value of 5 ng/ml. Furthermore, despite that tPA activity was very low, only 50% (mean value) was measured as stable complexes with PAI-1. Important increase of tPA:Ag was observed in various pathologies (cardiac infarction, septicemia, respiratory distress syndrome). In liver disease, tPA:Ag reached high levels up to 100 ng/ml. Impaired liver clearance can potentiate the increased concentration which results from endothelial release. In all patients with elevated tPA:Ag level, 70 to 100% of tPA was complexed to PAI-1. Excess release of PAI-1 accompanys the increased release of tPA as it is proved by presence of high residual PAI-1 activity. Addition of exogeneous tPA to these pathological plasmas induced a high increase in tPA-PAI-1 complexes. Venous stasis in normal population resulted in a parallel increase of tPA:Ag and tPA-PAI-1 complexes. Although about a two fold increase was obtained for both parameters, post venous stasis plasma presented a much higher fibrinolytic activity while PAI-1 activity was moderately elevated. tPA:Ag and tPA-PAI-1 complexes have diagnosis and prognosis value in various pathologies as indicators of stimulated release of fibrinolysis activator and inhibitor.
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PMID:Measurement of tPA and tPA-PAI-1 complexes by ELISA, using monoclonal antibodies: clinical relevance. 314 72

BACKGROUND--Aortic thrombosis is more frequent since the use of umbilical artery catheters in neonatal intensive care units. Some drugs or surgery are proposed to prevent complications; experience with tissue plasminogen activator (tPA) is still limited. CASE REPORT NO 1--A neonate, weighing 2400 g, developed respiratory distress requiring insertion of a catheter into her umbilical artery at H12. Ultrasonography on day 3 showed aortic thrombosis extending to the right renal artery which was confirmed by angiography. tPA 0.1 mg/kg was administered through the catheter, followed by 0.3 mg/kg/h for 3 hours and heparin, 100 IU/kg/hour for 54 hours. Angiography, performed 18 hours later, showed complete disappearance of the thrombosis. CASE REPORT NO 2--A neonate, weighing 2520 g suffered at 12 hours of life from seizures, apnea and bradycardia which required insertion of a catheter into her umbilical artery. Cyanosis of the right leg with weakening of femoral pulsations, 14 hours later, lead to the diagnosis of aortic thrombosis which was confirmed by aortography. The patient was given tPA 0.1 mg/kg followed by 0.3 mg/kg/h for 3 hours and heparin 100 IU/kg/hour for 6 hours. Amplitude of femoral pulsations strikingly increased within 6 hours with the disappearance of cyanosis. CONCLUSION--These results suggest that tPA can be useful in neonates presenting with aortic thrombosis.
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PMID:[Use of tissue plasminogen activator in the treatment of aortic thrombosis in newborn infants]. 778 May 51

We studied the activation pattern of clotting, fibrinolysis, and kinin-kallikrein during the first 5 d of life in 10 preterm infants with signs of severe idiopathic respiratory distress syndrome (IRDS) after birth (IRDS group) and in 12 healthy preterm infants (reference group). We found systemic activation of clotting, fibrinolysis, and kinin-kallikrein in the IRDS infants within 12 to 24 h of birth, represented by increased median thrombin-antithrombin III complex formation (90 ng/mL versus 10 ng/mL in the reference group, p < 0.05), increased mean tissue-type plasminogen activator plasma concentrations (11.8 ng/mL versus 3.5 ng/mL in the reference group, p < 0.05), and increased mean plasma kallikrein activity (182.6% versus 162.0% of maximal activated human plasma in the reference group, p < 0.05), respectively. Clotting activation was accompanied by a significant decrease of the platelet count. Clotting and fibrinolytic activity decreased in the IRDS group during the first 2 to 3 d of life. Kinin-kallikrein activation was accompanied by decreased plasma kallikrein inhibitor activity values and did not change throughout the study period. Plasma factor XII activity was not significantly increased in the IRDS infants during the first 2 d of life but did significantly increase thereafter. The cause of simultaneous activation of clotting, fibrinolysis, and kinin-kallikrein in our IRDS infants has not yet been clarified. However, this activation process may contribute to lung injury such as that described in the adult respiratory distress syndrome.
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PMID:Activation of the plasma clotting, fibrinolytic, and kinin-kallikrein system in preterm infants with severe idiopathic respiratory distress syndrome. 787 86

The serum plasminogen status in 35 preterm infants with or without respiratory distress syndrome (RDS) was determined in the first few hours of life. Blood samples for plasminogen testing (Synthetic chromogenic substrate method; Stachorm PLG. Diagnostica Stago) were obtained from a peripheral vein within six hours after birth. Among 35 infants, 20 infants who were in stable clinical condition served as the control group. Fifteen developed RDS with clinical, laboratory and radiological findings. The mean plasma plasminogen levels were found to be similar in the two groups (p > 0.05 by Mann-Whitney U test). These findings are discussed along with our previous findings showing normal tissue plasminogen activator (tPA) but lower D-dimer and higher plasminogen activator inhibitor (PAI) levels within the first few hours of life in preterm infants who later developed RDS compared to the control group.
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PMID:Plasma plasminogen levels in early respiratory distress syndrome. 870 84

This study was undertaken to determine whether simultaneous activation of clotting, fibrinolysis, and kinin-kallikrein is associated with disease severity in preterm infants with neonatal respiratory distress syndrome (RDS), during the first 5 d of life. In the infants with severe RDS, we found activation of clotting, fibrinolysis, and kinin-kallikrein within 6-12 h of birth, indicated by increased thrombin-antithrombin III complex formation [22.5 ng/ml versus 1.4 ng/ml (median values) in the mild/moderate RDS infants, p < 0.001], increased tissue-type plasminogen activator plasma concentrations [5.1 ng/ml versus 2.6 ng/ml (median values) in the mild/moderate RDS infants, p < 0.01], and increased plasma kallikrein activity [198% versus 189% of maximal activated human plasma (median values) in the mild/ moderate infants, p < 0.01], respectively. Thrombin generation, tissue-type plasminogen activator release, and kallikrein activity did not change significantly in the severe RDS group throughout the study. In these infants, kallikrein activity was accompanied by lower values of plasma kallikrein inhibitory activity. Activation of clotting, fibrinolysis, and kinin-kallikrein was accompanied with a transient decrease of the neutrophil count and a steady decrease of the platelet count in the severe RDS group. The studied parameters of clotting and fibrinolytic and kinin-kallikrein activation were significantly correlated with continuous measures of RDS severity. We, therefore, suggest that this activation process likely contributes to respiratory insufficiency in neonatal RDS.
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PMID:Disease severity is correlated with plasma clotting and fibrinolytic and kinin-kallikrein activity in neonatal respiratory distress syndrome. 897

Exogenous plasminogen activators (PAs), such as streptokinase (SK) and tissue plasminogen activator (tPA), have been shown to significantly improve the mortality of patients with acute myocardial infarction. However, reperfusion of the myocardium is associated with neutrophil activation and infiltration into the infarct region. Plasminogen activators influence neutrophil function in vitro, but no data exists regarding the effect of exogenous PAs on inflammation in vivo. Therefore, we evaluated the effect of PAs on inflammation using the carrageenan-induced rat footpad inflammation model. The magnitude of carrageenan-induced inflammation was determined by water-displacement and neutrophil infiltration, following administration of either tPA or SK to Sprague-Dawley rats. tPA (12 mg/kg) inhibited carrageenan-induced inflammation (p < .01). In contrast, administration of SK (40,000 U/kg) enhanced inflammation. These results suggest that exogenous PAs influence the inflammatory process but specific PAs differ in their actions. Ultimately, these differences may influence the efficacy of these agents in the management of acute myocardial infarction and lead to further evaluation of tPA in other inflammatory diseases such as acute respiratory distress syndrome (ARDS) and rheumatoid arthritis (RA), in which neutrophil-mediated injury is likely.
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PMID:Antiinflammatory activity of tissue plasminogen activator in the carrageenan rat footpad model. 903 37

Little is known on the haemostatic profiles of human microvascular endothelial cells (MVEC) from different tissues. In addition it is not known whether MVEC from patients display the same haemostatic pattern as MVEC coming from healthy controls. To address these questions MVEC from human lung and brain were isolated and stimulated with tumour necrosis factor alpha (TNF) and E. coli lipopolysaccharide (LPS) for 24 h. The level and the kinetics of procoagulant activity (PCA) and thrombomodulin (TM) expression were found to be different depending on the tissue of origin and on the agonist used. In particular, the inducible PCA was higher in lung than in brain MVEC, an observation that may be related to the frequency of lung involvement in septic shock. Differences were also observed for tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) with MVEC supernatants or cell lysates. These variables were then measured in lung MVEC purified from patients with acute respiratory distress syndrome (ARDS) and compared to controls. Cells from ARDS patients constitutively expressed more PCA and PAI-1 than controls. The fibrinolytic potential, expressed as t-PA/PAI-1 ratio, was lower in ARDS than in lung MVEC. It is concluded that MVEC display different haemostatic features depending on the tissue they come from and that lung MVEC from ARDS patients present a procoagulant profile when compared with those from controls.
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PMID:Haemostatic properties of human pulmonary and cerebral microvascular endothelial cells. 906 14

Because neutrophils contribute to reperfusion injury associated with acute myocardial infarction (MI), and because tissue plasminogen activator (tPA) is often used in the management of MI, we evaluated the effect of tPA on superoxide (O2.-) production by human neutrophils in vitro. We found that adding increasing amounts of tPA significantly (r = 0.89, P < 0.025) and progressively reduced O2.- generation by neutrophils treated with phorbol myristate acetate (PMA) in vitro. Furthermore, adding tPA that had been previously treated with the protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone HCl (PPACK), also decreased neutrophil O2.- generation in vitro (P < 0.05). In contrast, adding L-arginine, a component of the tPA preparation and a precursor of nitric oxide (NO), did not inhibit PMA-induced neutrophil O2.- production. Also, adding increasing concentrations of tPA did not reduce (P > 0.05) the concentrations of O2.- produced by xanthine oxidase (XO) in vitro. Our findings suggest that tPA reduces neutrophil O2.- generation by a mechanism that is not related to L-arginine, is not dependent on tPA proteolytic activity, and is not a function of direct scavenging. This property may account for some of the effectiveness of tPA in the treatment of MI and/or make tPA valuable for treating acute respiratory distress syndrome (ARDS) or other inflammatory disorders involving neutrophil O2.- production.
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PMID:Tissue plasminogen activator (tPA) inhibits human neutrophil superoxide anion production in vitro. 917 19

Because plasminogen activators (PA) may participate in the inflammatory process associated with the acute respiratory distress syndrome (ARDS), we measured the effect of tissue plasminogen activator (tPA) on inflammation and acute lung leak caused by intratracheal instillation of IL-1alpha (50 ng) into male (300-400 g) Sprague-Dawley rats. Lung leak, lung myeloperoxidase (MPO) activity, and lung lavage neutrophil counts were increased in rats given IL-1 intratracheally compared to control rats that were given saline intratracheally. Giving tPA (12 mg/kg) intraperitoneally increased lung tPA concentration and reduced acute lung leak in rats given IL-1 intratracheally (p < .01; lung leak index for sham-treated rats: 0.040 + 0.001, n=6; IL-1: 0.10 + 0.01, n=10; tPA + IL-1: 0.050 + 0.002, n=6). In contrast, administering tPA did not change IL-1-induced increases in lung lavage neutrophils or lung MPO activity (sham: 0.003 x 106 + 0.001 x 10(6) cells; IL-1: 2.9 x 10(6) + 0.4 x 10(6) cells; tPA + IL-1: 2.7 x 10(6) + 0.4 x 10(6) cells; and sham: 0.6 + 0.2 U/g lung; IL-1: 11.2 + 2.9 U/g lung, tPA + IL-1: 11.1 + 1.6 U/g lung, respectively). Our results suggest that intraperitoneal tPA administration increases lung tissue tPA levels and decreases acute lung leak without reducing lung neutrophil infiltration in rats given IL-1alpha intratracheally. This work suggests that tPA may suppress neutrophil activation in vivo and accordingly have anti-inflammatory effects.
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PMID:Tissue plasminogen activator (tPA) inhibits interleukin-1 induced acute lung leak. 966 94


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