Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To discover the role of lysosomal enzyme release from polymorphonuclear (PMN) leukocytes during septicemia, plasma levels of PMN elastase were measured with a newly developed enzyme-linked immunosorbent assay for detection of the PMN elastase-alpha 1-proteinase inhibitor complex (E-alpha 1PI). Plasma samples from 41 patients were assayed continuously before and after major abdominal surgery. The patients were divided into a group without infection (group A) and two septicemia groups (survivors in group B and nonsurvivors in group C). The E-alpha 1PI levels of the 11 patients in group A without any signs of pre- or postoperative infection were in the normal range (a normal value of 86.5 +/- 25.5 ng/ml has been reported in 153 healthy subjects), except for a small increase to 208.8 +/- 25.6 ng/ml 12 hours after surgery. When septicemia was confirmed clinically in patients in groups B and C, the E-alpha 1PI levels rose on average to six times the norm in group B (649.9 +/- 116.3 ng/ml) and to more than 10 times the norm in group C (985.0 +/- 154.6 ng/ml). Peak values greater than 2,200 ng/ml could be measured in both groups. In patients in group B, the E-alpha 1PI levels returned to normal during recovery, while in those in group C they remained significantly elevated (560.5 +/- 174.7 ng/ml) until death. Correlations were demonstrated between the amount of elastase released into the circulation and the decrease in the activities of antithrombin III, coagulation factor XIII, and alpha 2-macroglobulin, as well as the increased C-reactive protein in plasma. We conclude that release of elastase and other lysosomal factors from PMN cells plays a major role in the pathobiochemical alterations during septicemia. In addition, significantly elevated E-alpha 1PI levels in the postoperative course seem to be a suitable indicator for onset and persistance of sepsis as well as of the severity of this disorder in patients after major surgery.
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PMID:Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery. 241 55

The level and functional activity of the major protease inhibitors in plasma and faecal extracts were analysed in 26 consecutive patients admitted during their first attack of acute severe colitis. The patients were retrospectively divided into two groups: one with total colitis and another with distal colitis. The patients with total colitis had a significantly lower alpha 2-macroglobulin level in plasma than normal individuals and patients with distal disease, whereas no difference in the levels of alpha 1-protease inhibitor, antichymotrypsin, antithrombin III, and alpha 2-antiplasmin was noted between the two groups. The protease-inhibiting capacity was saturated, and free proteolytic activity was present in the faecal extracts. In the extracts complex formation was demonstrated between leukocyte proteases and the antiproteases alpha 1-protease inhibitor and alpha 2-macroglobulin. It is concluded that the low plasma level of alpha 2-macroglobulin in patients with severe total colitis is mainly due to a consumption caused by complex formation with proteases, as earlier demonstrated in patients with acute pancreatitis and sepsis.
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PMID:Protease inhibitors in plasma and faecal extracts from patients with active inflammatory bowel disease. 242 96

Vitronectin, also known as serum-spreading factor or S-protein, mediates cell adhesion and inhibits formation of the membrane-lytic complex of complement and the rapid inactivation of thrombin by antithrombin III in the presence of heparin. Vitronectin is normally present in plasma at a concentration of approximately 300 micrograms/mL. The investigators quantified plasma vitronectin with an enzyme-linked immunosorbent assay and visualized reduced and nonreduced vitronectin by immunoblotting after separation of plasma or serum by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The concentration of plasma vitronectin was markedly reduced in some patients with disseminated intravascular coagulation, especially in those with liver failure; it was near normal in patients with metastatic cancer and acute leukemia. Patients with vitronectin levels less than 40% normal invariably had low fibrinogen and antithrombin III and a prolonged prothrombin time. In both normal and patient plasmas there was heterogeneity in the ratio of the 75,000- and 65,000-mol wt polypeptides of reduced vitronectin: 18% had mostly the 75,000-mol wt polypeptide, 59% had roughly equal amounts of the two polypeptides, and 22% had mostly the 65,000-mol wt polypeptide. This polymorphism is inherited and appears to be due to two alleles that are present with approximately equal frequency. The blotting patterns of vitronectin in reduced and nonreduced plasmas were largely unaltered in plasma of patients with defibrination syndrome, fibrinolysis, liver failure, sepsis, metastatic cancer, and acute leukemia. There was no evidence of fragmentation of vitronectin or formation of the disulfide-bonded complex of vitronectin and thrombin-antithrombin III that is found when blood is clotted. Thus these results corroborate in vitro observations that the liver is the major source of plasma vitronectin, suggest that vitronectin may become depleted during disseminated intravascular coagulation, and define a genetic polymorphism of vitronectin.
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PMID:Plasma vitronectin polymorphism in normal subjects and patients with disseminated intravascular coagulation. 245 67

We have developed a specific and sensitive ELISA for the measurement of the TAT in human plasma. The assay follows the sandwich principle and uses two different antibodies directed against human thrombin and human antithrombin III, respectively. The anti-thrombin antibody population used for coating was purified by immunoadsorption on immobilized prothrombin and thrombin, respectively. Antithrombin III antibodies were conjugated with peroxidase. Plasma samples containing TAT were incubated in polystyrene tubes coated with anti-thrombin antibodies; after washing, peroxidase-conjugated antithrombin III antibodies were added and bound enzyme activity was subsequently measured using o-phenylenediamine. The assay was calibrated with definite concentrations (2.0 to 60 micrograms/l) of preformed purified TAT added to TAT-poor plasma. Plots of absorbance at 492 nm against TAT concentrations revealed a linear correlation (r = 0.98). A reference range from 0.85 to 3.0 micrograms/l was calculated from TAT concentration in plasma samples from 88 healthy donors (mean value +/- SD: 1.45 +/- 0.4 micrograms/l). In patients with deep vein thrombosis confirmed by phlebography (n = 15), TAT was found up to 7-13 micrograms/l. Patients with septicemia associated with a consumption coagulopathy (n = 10) showed markedly increased TAT values (greater than or equal to 10 micrograms/l). From these data it can be concluded that measurement of TAT might be a parameter for detection of a latent clotting pathway activation.
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PMID:Determination of human thrombin-antithrombin III complex by enzyme immunoassay. 246 14

We have shown previously that fluid phase platelet-activating factor (PAF) can enhance or "prime" polymorphonuclear (PMN) responses to subsequent stimulation with agonists such as formyl-methionine-leucine-phenylalanine (FMLP). Since thrombin induces PAF production in endothelial cells, we tested whether this thrombin-provoked endothelial PAF primes responses of marginated PMNs. Monolayers of human umbilical vein endothelial cells were exposed to either thrombin (0.5-5.0 units/ml) or buffer for up to 5 min and then PMNs were layered on top of the endothelial cells. After a further 5 min incubation, the PMNs were stimulated with a suboptimal concentration of FMLP (10(-7) M), and their superoxide production, elastase release, adhesion to endothelium, and capacity to cause endothelial cell lysis and detachment were assessed. Thrombin pretreatment significantly enhanced each of these FMLP-stimulated neutrophil responses. The extent of this enhancement correlated with both the dose and duration of thrombin treatment of endothelial cells and also the duration of PMN incubation with thrombin-exposed endothelium. Evidence that the augmentation was due to endothelial-derived PAF was obtained as follows: (1) thrombin induced [3H]acetate incorporation into endothelial PAF (assayed in lipid extracts); (2) antithrombin III conjointly inhibited this [3H]acetate uptake and prevented the priming effect of thrombin-treated endothelium on PMN responses; and (3) the PAF receptor antagonist BN52021, when preincubated with PMNs, also effectively blocked the enhancement of PMN responses. We conclude that thrombin stimulation of endothelial cells initiates a sequence of events culminating in the production of PAF--a membrane phospholipid capable of priming marginated PMNs. We suggest that this coagulation-fostered endothelial/PMN interaction may underlie a paracrine response that may potentiate PMN-mediated endothelial injury during sepsis and other thrombin-generating disorders.
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PMID:Thrombin-treated endothelium primes neutrophil functions: inhibition by platelet-activating factor receptor antagonists. 254 22

Plasma antithrombin III (ATIII) levels decrease early during gram-negative septicemia, and even a moderate decrease in this major inhibitor of the coagulation system is associated with serious disseminated intravascular coagulation (DIC). Herein the efficacy of high-dose (at least 250 units/kg) ATIII supplementation in animal models of Escherichia coli endotoxemia or bacteremia is reported. An endotoxemic rat model demonstrated that: (1) DIC occurs very early, before the appearance of deleterious cardiovascular abnormalities; (2) ATIII prophylaxis attenuates DIC, metabolic dysfunction, and organ damage; (3) ATIII prophylaxis increases permanent survival; (4) ATIII treatment one hour after endotoxin challenge attenuates DIC, metabolic dysfunction, and organ damage, although not as well as when given prophylactically, and survival is not increased. An endotoxemic sheep pulmonary dysfunction model demonstrated that: (1) ATIII prophylaxis prevents the typical decrease in arterial oxygen partial pressure; (2) ATIII prophylaxis combined with alpha-1-proteinase inhibitor significantly attenuates indices of pulmonary dysfunction. An E. coli bacteremic baboon model demonstrated that ATIII prophylaxis and treatment significantly attenuate indices of DIC and organ damage and prevent death in an otherwise completely lethal dose bacterial challenge. In conclusion, prophylactic treatment with high doses of ATIII may be efficacious in disease states of impending disseminated intravascular coagulation, such as primary or secondary gram-negative septicemia.
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PMID:Efficacy of antithrombin III supplementation in animal models of fulminant Escherichia coli endotoxemia or bacteremia. 267 67

Hemorrhagic and thrombotic complications are common in sick preterm infants and may reflect inadequate regulation of coagulation. All neonates have low levels of the pivotal regulator antithrombin III (ATIII) compared with adults. Plasma levels of ATIII are very low in preterm infants and are further diminished in infants with respiratory distress, necrotizing enterocolitis, sepsis, or disseminated intravascular coagulation. Babies with lower levels of ATIII in the cord blood have been shown to have a worse outcome than neonates with levels appropriate for gestational age, including higher mortality and increased incidence of intracranial hemorrhages and catheter-related thromboses. The origin of severe ATIII deficiency is unknown. Therapies with plasma replacement or anticoagulation have decreased the incidence and severity of hemorrhagic and thrombotic complications in high-risk infants in several clinical trials. These data lay the groundwork and rationale for potential use of ATIII replacement in deficient preterm infants.
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PMID:Neonatal antithrombin III deficiency. 267 71

In order to further elucidate the pathophysiological significance of plasma proteolysis during septicemia, surgical patients with septicemia were studied by means of chromogenic peptide substrate assays. In fatal cases continuous low values for prekallikrein, plasminogen and antithrombin III were found until death. At autopsy a persistent septic focus was found in all but one of the fatal cases. Very low levels of prekallikrein during sepsis and reduced functional inhibition of plasma kallikrein in septic shock indicated a poor prognosis. In the survivors the parameters returned towards the normal range upon successful therapy. Furthermore the paper demonstrates the application of a new parameter, the proenzyme functional inhibition index (PFI-index) in patients with septicemia. The data reveal that by means of this parameter patients at high risk can be identified at an early stage of the disease.
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PMID:Uncontrolled plasma proteolysis: a major threat to the septicemic patient. 302 78

The prognosis of septicaemia depends on the occurrence of complications such as shock and coagulation defects. The damage to haemostasis is usually explained by the action of the main coagulation and fibrinolysis enzymes, thrombin and plasmin. This paper presents data concerning the role of a third protease, granulocytic elastase. 82 patients who had been admitted to our hospital with suspected septicaemia were examined. Septicaemia was proven in 22 patients by the growth of microorganisms in blood cultures, and was clinically diagnosed in 9 patients. The plasma levels of neutrophil elastase-like protease complexed to a1antitrypsin (a1AT-ELP) were measured by zone immunoelectrophoresis assay (ZIA). The a1AT-ELP values were significantly increased in the 31 septic as compared to the 51 non-septic patients. In patients with complicated septicaemia, negative correlations of a1AT-ELP with factor XIII and the coagulation inhibitor antithrombin III were demonstrable. Among the patients with septic complications, the 3 who survived exhibited a dramatic decrease of a1AT-ELP, whereas in the other 16 patients who died the levels remained elevated. It might be of therapeutic significance that in 9 patients receiving fresh plasma and AT III-concentrate substitution for DIC the a1AT-ELP levels dropped, whereas they remained high in the other septicaemia patients. There were no correlations between a1AT-ELP and the a2antiplasmin-plasmin complexes (a2AP-P1), but strong correlations with signs of coagulation. The data suggest an interaction of coagulation and elastase release, probably involving the Hageman factor.
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PMID:Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections. 329 74

74 patients treated in the intensive care unit for postoperative sepsis were prospectively documented. The severity of sepsis was monitored by a scoring system. Additionally, daily measurements of antithrombin III (AT-III) levels, thrombocytes and endotoxin plasma concentrations were performed. The sepsis score only discriminated between surviving and non-surviving patients. The sensitivity in predicting death due to sepsis was 94%, the specificity 80% in case that a sepsis score of 19 was achieved. In contrast, thrombocytes, endotoxin plasma concentrations and AT-III levels were not able to predict the final outcome, but could be correlated to the severity of sepsis. Since high score levels can also be caused by multiple organ failure due to other reasons, the septic condition of the patients should be defined in the future by the combination of this scoring system with the endotoxin or AT-III measurement.
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PMID:[Follow-up of infected patients in an intensive care unit using the "infection score," endotoxin and AT III determination]. 337 97


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