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)

Widespread intravascular coagulation is common in patients with sepsis. Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor. The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems. Multiple agents are being studied to correct these abnormalities. Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin. Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue. Bradykinin may offset hypotension in sepsis. Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis. Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin. There are no data to support the use of heparin or fibronectin, except in limited circumstances.
 ...
PMID:Modulators of coagulation. A critical appraisal of their role in sepsis. 162 18

The plasma kallikrein-kinin system is activated in Gram-negative sepsis and typhoid fever, two diseases in which bacterial products have been shown to initiate inflammation. Because a single intraperitoneal injection of bacterial cell wall peptidoglycan-polysaccharide polymers from group A steptococci (PG-APS) into a Lewis rat produces a syndrome of relapsing polyarthritis and anemia, we investigated changes in the role of the kallikrein-kinin system in this model of inflammation. Coagulation studies after injection of PG-APS revealed an immediate and persistent decrease in prekallikrein levels. High-molecular-weight kininogen levels decreased significantly during the acute phase and correlated with the severity of arthritis. Factor XI levels were decreased only during the acute phase. Antithrombin III levels remained unchanged, indicating that neither decreased hepatic synthesis nor disseminated intravascular coagulation caused the decreased plasma contact factors. Plasma T-kininogen (an acute phase protein) was significantly elevated during the chronic phase. PG-APS failed to activate the contact system in vitro. Thus the kallikrein-kinin system plays an important role in this experimental model of inflammation, suggesting that activation of this system may play a role in the pathogenesis of inflammatory bowel disease and rheumatoid arthritis in which bacterial products might be etiologically important.
 ...
PMID:Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation. 199 42

A 66-year-old male with chronic alcoholic liver injury was admitted on July 27, 1986 to our hospital with complaints of high fever, convulsion and skin erythema. He had consumed raw fish 3 days before, and had a scratch wound over the right arm and left leg because he had slipped in a small stream in the woods the day before admission. He was already in shock state with sepsis of V. vulnificus and DIC on admission. Although the treatment with ABPC, CP, CAZ, MINO for sepsis, and Heparin & Antithrombin III for DIC was immediately begun, he died only 10 hours after admission. On autopsy, the skin lesion revealed phlegmon with necrotizing angitis and the liver showed fatty changes with Mallory's body. The causative organism was detected from the blood and on autopsy from the skin wound, bile juice, liver, spleen, kidney and bone marrow, and its type was determined as a V. vulnificus serovar 4. It was suspected that the route of infection in this case was the raw fish rather than via the wound because the water in which he had been wounded was fresh water and the bacterium was not detected from the water, shells, nor moss existing there.
 ...
PMID:[A case of fatal sepsis due to Vibrio vulnificus]. 218 37

The relationship between serum elastase and antithrombin III was determined in septic surgical patients as a possible mechanism for intravascular thrombosis and hypercoagulability during sepsis. Eighteen patients with surgical infections and elevated white blood cell counts had their blood assayed daily for white blood cell count, serum elastase, and antithrombin III, until the patient's white blood cell count returned to normal. Antithrombin III was significantly lower (0.87%) when elastase was above the normal range (greater than 14.2 micrograms/ml). Elastase was significantly higher (30.6 micrograms/ml), when antithrombin III was less than normal. These data indicate that elevated serum elastase is associated with a significant reduction in circulating antithrombin III. Stimuli that increase serum elastase, i.e. surgery, trauma, or sepsis may promote intravascular thrombosis by the inhibition of antithrombin III at the blood-endothelial cell interface.
 ...
PMID:The inactivation of antithrombin III by serum elastase in patients with surgical infections. 224 Aug 57

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.
 ...
PMID:Determination of human thrombin-antithrombin III complex by enzyme immunoassay. 246 14

Alpha 1-antitrypsin-Pittsburgh (AT-P), a naturally occurring lethal mutation (358Met----Arg), has been genetically engineered (rAT-P). The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein. Because activation of the contact system is known to occur in gram-negative septicemia, the authors have hypothesized that the administration of rAT-P might modulate the course of this syndrome. Yorkshire piglets anesthetized with pentobarbital and infused with viable Pseudomonas aeruginosa (2 X 10(8) CFU) were untreated (Group I) or treated with rAT-P (Group II) and studied in a 6-hour protocol. Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen. In addition, rAT-P markedly reduced the serum levels of fibrinogen degradation products. Survival in Group II was significantly increased during 2-5 hours but not at 6 hours when the functional levels of rAT-P in plasma were the lowest. These results indicate that this recombinant inhibitor, even at low concentrations, affords protection in experimental gram-negative septicemia.
 ...
PMID:Recombinant alpha 1-antitrypsin Pittsburgh attenuates experimental gram-negative septicemia. 325 51

Antithrombin III concentrates offer a new therapeutic possibility for immediately increasing the inhibitory potential of plasma. Although heparin activates ATIII, thereby accelerating its consumption, it cannot increase the overall inhibitory capacity towards coagulation. The anticoagulant effect of heparin is in relation with the presence of sufficient amounts of ATIII. The intensive care of patients with liver failure, amniotic fluid embolism, heavy bleedings and septicemia was greatly aided by the substitution of ATIII. Disseminated intravascular coagulation was prevented or interrupted and there are observations suggesting that also shock lung and shock kidney are avoided. The substitution of ATIII allows an extremely extensive therapeutic plasmapheresis without the risk of thromboses.
 ...
PMID:Antithrombin III concentrates in intensive care. 634 78

Components of the plasma proteolytic enzyme systems were studied in 15 multiple trauma patients. There were 9 survivors and 6 fatal cases. All fatal cases had sepsis and/or post traumatic adult respiratory distress syndrome. Within the first day after trauma significantly reduced values were found for plasma prekallikrein (PKK), Hageman factor (HF) and Antithrombin III (AT III). In the survivors these parameters were normalized within the first five days after the injury. In the fatal cases, however, the same parameters remained reduced or declined during the observation period. The fatal cases also revealed a high frequency of positive ethanol gelation tests (EGT), elevated serum fibrin - fibrinogen degradation products (FDP) values and persisting low platelet counts. Analyses of plasma samples from both survivors and fatal cases, fractions by Sephadex G-150 gel filtration, demonstrated alpha 2-macroglobulin - plasma kallikrein complexes. These findings demonstrate activation of the kallikrein-kinin system as a part of pathological plasma proteolysis in multiple trauma patients. Persistent reductions of PKK, HF and AT III combined with positive EGT, elevated FDP values and reduced platelet counts indicate a poor prognosis.
 ...
PMID:Determination of components of the plasma proteolytic enzyme systems gives information of prognostic value in patients with multiple trauma. 634 78

The interaction of elastase isolated from human granulocytes with purified human antithrombin III was investigated. Antithrombin III did not display any inhibitory effect on granulocytic elastase. Dependent on enzyme concentration, however, granulocytic elastase induced progressive inactivation of antithrombin III leading to an almost complete loss of the thrombin inhibitory activity at a molar ratio of elastase: antithrombin III = 0.4:1 within 5 min at 25 degrees C. Antithrombin III is not drastically degraded by elastase as revealed by polyacrylamide gel electrophoretic and rocket immunoelectrophoretic investigations. However, characterization by two-dimensional immunoelectrophoresis with heparin in the first dimensional gel layer revealed a distinct change in the electrophoretic mobility of the inhibitor preincubated with elastase compared to native antithrombin III. This indicates that heparin binding sites of antithrombin III are occupied or affected by the elastase-induced peptide bond cleavage(s). Granulocytic proteinase inhibitors (eglin, Bowman-Birk inhibitor) proved to be highly effective in preventing the antithrombin III inactivation by degradation due to elastase. It is assumed that at least part of the antithrombin III consumption in diseases such as septicemia or endotoxemia is due to proteolysis by granulocytic proteinases. Application of specific inhibitors in the early phase of these ailments should be able to prevent this unspecific degradation of the endogenous antithrombin III.
 ...
PMID:Effect of human granulocytic elastase on isolated human antithrombin III. 678

Whole-blood chemiluminescence and levels of leukocyte proteases and plasma protease inhibitors were studied in 43 patients with acute, generalized peritonitis. An almost three-fold increase in whole-blood chemiluminescence was found in acute peritonitis, which may indicate activation or "priming" of the leukocytes by blood-borne factors. High levels of leukocyte elastase and neutrophil proteinase 4(3) were found in plasma and peritoneal exudate. Patients with sepsis had higher plasma levels of both proteases than other patients. Large variations in the plasma levels among patients decreased their sensitivity as markers of infectious complications during the postoperative period. The plasma levels of the protease inhibitors followed three different patterns of reaction. The acute phase proteins alpha 1-proteinase inhibitor and C1-inactivator, increased during the first week of disease, to normalise later in its course. alpha 2-macroglobulin, antithrombin III and alpha 2-antiplasmin were all decreased from onset and normalised later in the course, while secretory leukocyte protease inhibitor showed a slow decrease throughout the course of disease. In peritonitis exudate, the levels of the main protease inhibitors, alpha 1-Proteinase Inhibitor and alpha 2-Macroglobulin, were decreased, probably due to complexation and subsequent elimination, as a part of the defense against liberated leukocyte proteases. The immunoreactive and especially functional levels of the protease inhibitors alpha 2-Antiplasmin, Antithrombin III and C1-Inactivator were also decreased in the exudate, indicating an increased turn-over of these proteins through activation of the cascade systems and/or break-down by leukocyte proteases. In contrast to the other inhibitors, secretory leukocyte protease inhibitor showed higher levels in exudate than in plasma, and unexpectedly high exudate/plasma-quotients were seen in cases with colonic perforations. Degradation of complement factor 3 (C3) and decreased "opsonic capacity" were found in exudate. The "opsonic capacity" could be correlated to the levels of leukocyte proteases in the exudate, which indicates that degradation of complement factor 3 may have been at least partly due to the action of leukocyte proteases. Further depletion of complement factors in exudates of long-standing peritonitis or abscesses may create a vicious circle of deficient opsonisation and clearance of bacteria, as earlier reported for chronic pleural exudates.
 ...
PMID:Protease-antiprotease levels and whole-blood chemiluminescence in acute peritonitis. 822 20


1 2 3 Next >>