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

To better understand the role of granulocyte elastase (GE) in mediating tissue injury during sepsis, GE levels were measured in plasma and bronchoalveolar lavage fluid (BALF) in patients with septic shock (n = 16) and hemorrhagic shock (n = 30). Granulocyte elastase levels were compared to levels of alpha 1-protease inhibitor (alpha 1-PI). Results show that although plasma GE-alpha 1-PI complex was initially elevated in patients with hemorrhagic and septic shock, elevations in plasma GE-alpha 1-PI complex (831 +/- 241 micrograms/L) persisted in septic shock patients. alpha 1-Protease inhibitor levels in serum were increased, resulting in an inhibition of serum GE activity. Granulocyte elastase activity in BALF, however, was significantly higher in those patients with septic, as compared to hemorrhagic shock (31.4 +/- 25.8 versus 3.7 +/- 4.0 U/L, respectively). In addition GE levels were compared to other parameters, including respiratory index, blood neutrophil count, and plasma levels of endotoxin, fibronectin, and coagulation factor XIII. Significant correlations were observed between GE-alpha 1-PI and increased endotoxin concentration and decreased fibronectin and coagulation factor XIII levels. Significant correlation was found also between GE activity in BALF and respiratory index. These findings suggest that severe tissue damage occurred in patients with septic shock complicated by multiple-organ failure. Although GE activity appeared to be adequately inhibited by alpha 1-PI in blood, increased GE activity in local tissues, such as lung alveoli, may be responsible for significant local tissue injury during septic shock.
 ...
PMID:Role of granulocyte elastase in tissue injury in patients with septic shock complicated by multiple-organ failure. 198 43

Gram-negative bacterial sepsis is frequently associated with acute renal failure but the specific effects of lipopolysaccharide (LPS) and other bacterial products on kidney function are not known. Since either LPS or formyl-methionyl-leucyl-phenylalanine (FMLP)--a chemotactic peptide from bacterial cell walls--activate neutrophils (PMN) to release a number of potentially toxic factors in vitro, we determined the effect of adding PMN with LPS and/or FMLP to isolated perfused rat kidneys. Isolated rat kidneys perfused with LPS alone or LPS and normal PMN had normal glomerular filtration rates (GFR) and tubular Na reabsorption (TNa). Kidneys perfused with FMLP alone or FMLP and normal PMN also had normal GFR and TNa. In contrast, addition of PMN with both FMLP and LPS caused progressive renal dysfunction. For example, after 60 minutes of perfusion, GFR was reduced from 610 +/- 31 to 147 +/- 17 microliters/min/g and TNa from 97 +/- 1 to 72 +/- 2%, both P less than 0.01. Perfusion with the O2 metabolite scavengers catalase or dimethylthiourea afforded no protection while perfusion with the neutrophil elastase inhibitor Eglin C conferred substantial, but not complete, protection: GFR 492 +/- 34 microliters/min/g; TNa 91 +/- 3%. However, perfusion with both Eglin C and catalase completely prevented the toxic effects of LPS and FMLP-treated PMN on renal function. We conclude that in isolated kidneys, 1) the toxic effects of LPS requires FMLP-treated PMN and that 2) LPS and FMLP treated PMN cause progressive renal injury which is mediated by both O2 metabolites and neutrophil elastase.
 ...
PMID:Role of neutrophil derived oxidants and elastase in lipopolysaccharide-mediated renal injury. 205 18

Neutrophils are activated during sepsis. To find out whether granulocytes are further activated during hemodialysis with cellulosic and noncellulosic membranes, we compared the plasma levels of the main granulocyte components in patients with chronic uremia who were undergoing regular hemodialysis treatment and patients with acute renal failure with and without sepsis. During hemodialysis with cuprophane dialyzers, plasma-granulocyte elastase, in complex with alpha-proteinase inhibitor, and lactoferrin levels increased in patients who were undergoing regular hemodialysis treatment, but these levels increased further in patients with acute renal failure who did not have sepsis. Maximal neutrophil degranulation was observed in patients with acute renal failure and sepsis. There was only mild degranulation in all three groups during dialysis with dialyzers made of polysulfone. Our data demonstrate that neutrophil activation is increased in patients with acute renal failure, and it is increased further by superimposed sepsis. Cellulose-containing dialysis membranes introduce a further activation of neutrophils.
 ...
PMID:Neutrophil activation in acute renal failure and sepsis. 233 Dec 24

In human blood, cortisol is transported by a plasma protein known as corticosteroid-binding globulin (CBG). As anticipated from primary structure comparisons of CBG and alpha 1-proteinase inhibitor (A1-PI), CBG acts as a substrate for neutrophil elastase. However, unlike A1-PI, CBG does not alter the activity of this enzyme, but is cleaved by it at a single location close to its carboxy-terminus, and this reduces its molecular size by 5 kDa with the concomitant release of more than 80% of CBG-bound cortisol. Three small molecular size fragments are detected after elastase cleavage, and carbohydrate analysis of these fragments suggests that they represent the same polypeptide fragment which has been differentially glycosylated. To assess the biological significance of these observations, CBG was incubated with either mononuclear cells or granulocytes obtained from patients with acute inflammation (sepsis) and from a normal volunteer. Only granulocytes from septic patients reduced the mol wt of CBG by about 5 kDa and destroyed its steroid-binding activity. Preincubation with A1-PI prevented this, which demonstrates that neutrophil elastase plays a key role in this event. These results suggest a physiological role for CBG in the delivery of cortisol to sites of inflammation.
 ...
PMID:A role for corticosteroid-binding globulin in delivery of cortisol to activated neutrophils. 237 Feb 99

Plasma from 7 septic patients with positive blood cultures were studied. None of them presented either clinical or laboratory evidence of Disseminated Intravascular Coagulation. The white cells count varied between 5 and 45 X 10(9)/l. In plasma functional plasminogen levels varied between 25 and 45%, while those of alpha 2-antiplasmin were normal (80-105%). The levels of elastase ranged between 250 and 750 micrograms/ml. Leukocyte elastase digests plasminogen "in vitro" and is able to produce several fragments; one of them called mini-plasminogen lacking lysine binding sites; therefore it does not bind to lysine-Sepharose 4B. Two different behaviors were observed in the plasmatic plasminogen of these patients with respect to their binding capacity to lysine-Sepharose 4 B. 3 patients had plasminogen which did not bind to lysine-Sepharose 4 B; the other 4 had two different components, one of which bound to lysine-Sepharose 4 B and another one which did not bind. Previous studies "in vitro" have shown that leukocyte elastase modifies alpha 2-antiplasmin, initially producing a non-plasminogen binding form. A free alpha 2-antiplasmin (non-plasminogen binding form) was detected in the plasma of these patients with sepsis by crossed immunoelectrophoresis with plasminogen in the first dimension. It seems tenable that high levels of leukocyte elastase could be responsible for these findings although, the possible relationships to leukocyte elastase still remain to be proven but could possibly explain this effect.
 ...
PMID:Mini-plasminogen like molecule in septic patients. 244 46

Of 64 polytraumatized patients with a mean injury severity score of 33.1, 42 showed marked systemic release of thromboxane B2 and granulocyte elastase during the initial 18 hours after trauma, reaching peak arterial levels of greater than 1,000 pg/ml and ng/ml, respectively. If those patients ("responders": plasma TXB2 greater than 250 pg/ml) were compared with the remaining 22 ("non-responders": TXB2 less than 250 pg/ml) the following became obvious: "Late" mortality (greater than 3 d) was 31% in responders, which is significantly higher than in non-responders (9%). No correlation was observed between "early" mortality (less than 3 d) and mediator release. There was no difference in the incidence of the adult respiratory distress syndrome (ARDS) (38% versus 32%) or the late sepsis syndrome (17% versus 18%) between responders and non-responders. Morbidity, however, differed markedly in that ARDS in responders was associated with significantly higher elastase levels, a higher mortality and 10 times higher incidence of sepsis as compared to responders without ARDS. ARDS in non-responders, by contrast, did not change elastase maxima or the mortality rate as compared to non-responders without ARDS. It is concluded that TXB2 is not a predictor of posttraumatic ARDS, but is related to a complicated course, in particular to sepsis and mortality. Elastase with high probability predicts ARDS and/or the late sepsis syndrome. Simultaneous determination of TXB2 further enhances the predictive value of elastase.
 ...
PMID:[Thromboxane A2 and granulocyte elastase after severe trauma--relationship to complications and survival rates]. 260 65

Plasma levels of granulocyte elastase and C-reactive protein were measured 0, 12, 24 and 48 h after suspicion of septicemia in 64 critically ill patients. Initial elastase levels were higher in 16 bacteremic patients (mean 773 micrograms/l) than in 48 non-bacteremic patients (mean 341 micrograms/l, p less than 0.01), whereas C-reactive protein levels were similar in both groups. At a level of 100% sensitivity for the early detection of septicemia, increased elastase was less than 50% specific, indicating limited diagnostic usefulness in this setting.
 ...
PMID:Granulocyte elastase compared to C-reactive protein for early diagnosis of septicemia in critically ill patients. 313 13

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.
 ...
PMID:Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections. 329 74

Our data are consistent with the assumption that in early septicemia polymorphonuclear granulocytes are sequestered and release lysosomal elastase locally into the respiratory tract and into the circulation.
 ...
PMID:Granulocyte elastase and white cell counts in septic pigs. 330 41

Staphylococcus aureus is known to produce three very active extracellular proteinases. One of these enzymes, a cysteine proteinase, after purification to homogeneity was found to degrade insoluble bovine lung elastin at a rate comparable to human neutrophil elastase. This enzyme had no detectable activity against a range of synthetic substrates normally utilized by elastase, chymotrypsin, or trypsin-like proteinases. However, it did hydrolyze the synthetic substrate carbobenzoxy-phenylalanyl-leucyl-glutamyl-p-nitroanilide (Km = 0.5 mM, kcat = 0.16 s-1). The proteolytic activity of the cysteine proteinase was rapidly and efficiently inhibited by alpha 2-macroglobulin and also by the cysteine-specific inhibitor rat T-kininogen (Ki = 5.2 X 10(-7) M). Human kininogens, however, did not inhibit. Human plasma apparently contains other inhibitors of this enzyme, since plasma depleted of alpha 2-macroglobulin retained significant inhibitory capacity. The elastolytic activity of this S. aureus proteinase and its lack of control by human kininogens or cystatin C may explain some of the connective tissue destruction seen in bacterial infections due to this and related organisms such as may occur in septicemia, septic arthritis, and otitis.
 ...
PMID:Degradation of elastin by a cysteine proteinase from Staphylococcus aureus. 342 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>