Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mediterranean spotted fever, a tick-borne rickettsiosis caused by Rickettsia conorii, may lead to small-vessel or deep-vein thrombosis. In order to evaluate the role of endothelial cell alteration in this lesion, we infected human endothelial cells derived from umbilical veins with R. conorii. We report the induction of two previously unreported prothrombotic mechanisms in rickettsial disease: (i) a progressive decline in thrombomodulin antigen and (ii) early expression of tissue factor, and, as described for R. rickettsii infection, later release of von Willebrand factor from Weibel-Palade bodies. Thrombomodulin expression in infected endothelial cells, measured by the thrombin-dependent activation of protein C or flow cytometric analysis, decreased steadily between 4 and 24 h after inoculation with rickettsiae. R. conorii infection induced tissue factor expression, measured by clotting assay and flow cytometric analysis, which was detectable 2 h postinoculation, reached its maximum 4 h postinoculation, and progressively decreased thereafter. Infection resulted in a relatively late release of von Willebrand factor antigen into the culture medium. A double-label immunofluorescence assay for the simultaneous evaluation of von Willebrand factor and R. conorii showed that the depletion of cytoplasmic von Willebrand factor stored in Weibel-Palade bodies was due to a direct effect of the intracellular R. conorii. These disturbances of endothelial function observed with R. conorii-infected cells may provide a paradigm for the elucidation of thrombotic pathobiology with Mediterranean spotted fever.
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PMID:von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells. 132 57

To study the effect of infection, a frequent complication of fulminant hepatic failure (FHF), on the release of elastase from polymorphonuclear leucocytes and its inhibition in circulation we have measured the concentrations of alpha 1-antitrypsin, which binds and inhibits elastase in the circulation, and of elastase-alpha 1-antitrypsin complex, in 30 patients with FHF. Elastase-alpha 1-antitrypsin complex was significantly increased in FHF as compared to controls (303 +/- 51 micrograms/l compared to 37 +/- 5 micrograms/l; n = 10; P less than 0.001) demonstrating activation of leucocytes in FHF. Infection caused greater release of leucocyte elastase, complex levels were significantly greater in patients who were infected when compared to those who were not (463 +/- 84 micrograms/l; n = 13 compared to 180 +/- 46 micrograms/l; n = 17; P less than 0.01). Also patients who survived had significantly lower complex levels than those who did not (212 +/- 49 micrograms/l; n = 18 compared to 440 +/- 94 micrograms/l; n = 12; P less than 0.02). alpha 1-Antitrypsin activity was not significantly different from control subjects (0.99 +/- 0.06 U/ml compared to 0.97 +/- 0.05 U/ml). However alpha 1-antitrypsin activity was significantly higher in patients who survived (1.17 +/- 0.05 U/ml; n = 18) compared to those who did not (0.71 +/- 0.03 U/ml; n = 12; P less than 0.001) and patients who died had significantly lower levels than control subjects (P less than 0.01) indicating the importance of maintenance of normal inhibitor levels in patients with FHF. The leucocyte activation and release of elastase in FHF was linked to activation of the coagulation system; elastase--alpha 1-antitrypsin complex levels correlated significantly with thrombin-antithrombin III complex levels (r = 0.68; P less than 0.001) and inversely with fibrinogen (r = -0.71; P less than 0.001).
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PMID:Increased elastase-alpha 1-antitrypsin complex in fulminant hepatic failure: relationship to bacterial infection and activation of coagulation. 177 69

Sternal or mediastinal infection after heart operations occurs infrequently but carries a high cost in money, morbidity, and mortality. At our hospital, Staphylococcus nonaureus causes most of these infections and is uniformly sensitive to vancomycin. In a prospective study of 416 patients having cardiac operations, randomized by hospital record number, topical vancomycin was applied to the cut sternal edges in 223 patients (group V) and was omitted in the control group (C) of 193 patients. The vancomycin was applied in a hemostatic paste of topical thrombin and powdered absorbable gelatin; in the control group only the hemostatic paste was applied. All patients received prophylactic systemic antibiotics for 2 days. Sternal infection occurred in one patient in group V (0.45%) and in seven patients in group C (3.6%) (p = 0.02). Infection also correlated with longer operative times (p = 0.027). By multivariate testing, vancomycin (p = 0.013) and shorter operative times (p = 0.014) independently predicted reduced infection rates. In the one patient with an infection in group V, Staphylococcus aureus was cultured; this organism was also cultured in two patients in group C, with Staphylococcus nonaureus being the culprit in the other five patients with sternal infections in group C. Topical vancomycin applied to the cut sternal edges reduces the risk of postoperative sternal infection.
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PMID:Reduction of sternal infection by application of topical vancomycin. 279 69

Eleven patients with terminal renal insufficiency requiring dialysis were treated with 3 X 2 g cefotaxime in an open study lasting five days when the clinical findings strongly indicated a serious bacterial infection. The effect of the administration of the high-dose antibiotic on the coagulation system (Quick test, partial thromboplastin time, thrombin time, antithrombin III and platelets) and on brain function (EEG) was investigated. The serum levels showed that the serum concentrations were not abnormally high in cases of terminal renal insufficiency requiring dialysis. In contrast to previous investigations in other beta-lactam antibiotics, no changes in the coagulation system or EEG occurred. On the basis of these findings, no reduction in the dose appears necessary for cefotaxime, if therapy does not exceed five days.
Infection 1985
PMID:Tolerance in patients with terminal renal insufficiency of high doses of cefotaxime. 405 48

Pigs were infected with highly virulent (Tengani '62), with moderately virulent (DR '79) African swine fever (ASF) virus, or with virulent hog cholera (HC) virus. Changes in platelet counts, selected coagulation assays and concentrations of factor VIII-related antigen (VIIIR:Ag) were monitored. Permeability of aortic endothelium was studied after the injection of Evan's blue dye on various days after infection with DR '79 ASF virus. Virulent ASF virus caused prolongation of the activated partial thromboplastin time (APTT), 1-stage prothrombin time, and thrombin clotting time as early as postinoculation day (PID) 4. These changes became progressively more severe until death. Both virulent HC and DR'79 viruses induced an increase APPT and thrombin clotting time at PID 3 to 4, only occasionally did the prothrombin time increased significantly (P less than 0.01). The APPT began to decrease on PID 7 and 8, but only DR'79-infected pigs lived long enough to regain a normal APTT. Infection by ASF viruses caused acute thrombocytopenia after PID 6 and platelet counts of HC virus-infected pigs decreased progressively from the onset of fever to levels of 1 to 2 X 10(5)/mm3 at PID 6 to 7. All ASF virus-infected pigs had an increase in VIIIR:Ag beginning at PID 3, with maximum increases at PID 6 to 7. Hog cholera virus infection did not cause consistent changes in levels of VIIIR:Ag. Pigs infected with DR'79 virus did not have increased vascular permeability to Evan's blue dye during infection; however, there was markedly decreased staining of the aorta after pigs became thrombocytopenic.
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PMID:Coagulation changes in African swine fever virus infection. 644 89

Infection by Porphyromonas gingivalis is strongly associated with adult periodontitis, with proteinases from this bacterium now considered to be important virulence factors. In order to investigate possible pathological functions of these enzymes, we examined the effect of both free and vesicle-bound forms of the two major cysteine proteinases (gingipains) of P. gingivalis on plasma clot formation by using thrombin time (TT) measurements. Both Lys-gingipain (gingipain-K) and Arg-gingipain (gingipain-R) prolonged plasma TT in a dose- and time-dependent manner, and this was also found with vesicles which are the biological carriers of P. gingivalis proteinases. The increase in plasma TT by vesicles could be completely reversed by treatment with nonspecific cysteine proteinase inhibitors but only partially by compounds selective for either gingipain-K or gingipain-R. Preincubation of vesicles with a gingipain-K-specific inhibitor (z-FK-ck) reduced plasma TT more than a gingipain-R-specific inhibitor (leupeptin), suggesting that under physiological conditions gingipain-K was more effective in fibrinogen destruction. Each purified enzyme also markedly increased fibrinogen TT, gingipain-R being fourfold more potent than gingipain-K. However, in plasma, gingipain-R was ineffective because of the inhibitory effect of albumin. These results imply that cysteine proteinases, especially gingipain-K, abrogate the clotting potential of fibrinogen and, therefore, may contribute to the bleeding tendency and to persistent inflammation in periodontitis sites infected with P. gingivalis.
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PMID:Effect of free and vesicle-bound cysteine proteinases of Porphyromonas gingivalis on plasma clot formation: implications for bleeding tendency at periodontitis sites. 759 Nov 49

Infection of naive North American horses with 10(4) cell culture infectious doses (CCID50) of virulence variants of African horsesickness virus (AHSV), designated AHSV/4SP, AHSV/9PI, and AHSV/4PI, reproduced three classical forms of African horsesickness: acute (pulmonary), subacute (cardiac), and febrile, respectively. Distinct clinicopathologic and hemostatic abnormalities were associated with each form of disease. Hemostatic abnormalities included increased concentration of fibrin degradation products and prolongation of prothrombin, activated partial thromboplastin, and thrombin clotting times. Hemostatic findings indicated activation of the coagulation and fibrinolytic systems with clotting factor consumption in acute and subacute cases of African horsesickness. Hematologic abnormalities in acute and subacute cases of African horsesickness included leukopenia, decreased platelet counts, elevated hematocrit, and increased erythrocyte counts and hemoglobin concentration. Leukopenia was characterized by lymphopenia, neutropenia, and a left shift. Increased levels of serum creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, hypocalcemia, hypoalbuminemia, hypoproteinemia, and elevated creatinine, phosphorus, and total bilirubin levels were present in some but not all horses. Metabolic acidosis, indicated by decreased total bicarbonate and increased lactate and anion gap, was present in horses with the acute form of disease. Mild thrombocytopenia and leukopenia were occasionally associated with the febrile form of disease. These results suggest a role for intravascular coagulation in the pathogenesis of African horsesickness.
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PMID:Clinical pathology and hemostatic abnormalities in experimental African horsesickness. 777 Oct 50

The kinetics of drug release from fibrin adhesive agent (consisting of fibrinogen, factor 8, thrombin, aportinin and calcium chloride)-antibiotic compound and efficacy on rat experimental osteomyelitis were studied. To enhance the slow release activities of antibiotic, a mixture of fibrin clots was freeze-dried. Effects of freeze-drying were to make a fibrin clot an interlinked pore and to increase crosslinking rate containing an antibiotic. A diffusion test from aminoglycoside (Arbekacin Sulfate: 200 mg) compound was carried out. In vitro study freeze-dried antibiotic compound (FFAC: 1 cm3) was placed in saline (3 ml). The saline was replaced every 48 h and the previous solution was stored at -45 degrees C until assay. The result was that a concentration of 0.4 mg/l, sufficiently high to control Staphylococcus aureus strain IM2-42, was maintained within nine exchanges of saline after 18 days. In vivo animal experiments, FFAC (2 x 2 x 3 mm) were tested in rats with established Staphylococcus aureus osteomyelitis in the proximal tibia. The animals were observed for radiographic signs of infection and tissue was examined histopathologically. Bacterial counts by bone cultures were statistically lower in rats implanted with FFAC than in those only given a drug-free FFC and curettage. Radiographical and histological observations also showed beneficial effects of the FFAC. The results suggest that the FFAC provide a simple drug delivery system, and may be a promising alternative treatment for osteomyelitis.
Infection
PMID:The sustained release of antibiotic from freeze-dried fibrin-antibiotic compound and efficacies in a rat model of osteomyelitis. 942 55

Antibiotics (ABs) delivered from fibrin were evaluated for control of multi-drug resistant (MDR) Staphylococcus aureus. ABs having low aqueous solubility (< or = 1 mg/ml) were encapsulated by fibrin (composed of fibrinogen, thrombin, Factor XIIIa and calcium chloride) and examined. Electron microscopy revealed fibrin-caged, tetracycline crystals that were 0.26 to 2.8 microns in size and bound within the reticular matrix. Antibiograms documented that S. aureus ATCC 27659 was resistant to erythromycin (ERY), penicillin G (PEN), streptomycin (STR), sulfamethoxazole-trimethoprim (SXT) and tetracycline (TET). However, low solubility formulations of STR (10 mg/ml) or SXT (0.5 mg/ml), delivered from fibrin and evaluated by the agar disk diffusion assay, produced zones of growth inhibition after 18-24 h at 37 degrees C in vitro, indicating renewed susceptibility of S. aureus ATCC 27659 to these ABs. ERY, PEN and TET were unable to overcome resistance at concentrations up to 10 mg/ml. In vivo, intraperitoneal (i.p.) injection of 150 mg/kg STR delivered from fibrin resulted in 100% survival of rats with MDR S. aureus peritonitis as compared with control rats receiving i.p. STR (150 mg/kg) in 0.9% saline. The results demonstrate that some low solubility ABs delivered from fibrin are efficacious in controlling infection mediated by MDR S. aureus.
Infection
PMID:Subverting bacterial resistance using high dose, low solubility antibiotics in fibrin. 1002 3

To date there have been no standard methods for assessing the thrombogenicity of central venous catheters. A procedure for testing the thrombogenicity of intravenous lines such as the silver-impregnated catheter by continuous blood flow in vitro was therefore developed. For this test, fresh blood was drawn from healthy human donors and anti-coagulated with sodium citrate (1:9). All material tested (catheter tubes with and without silver manufactured in the same way, polyethylene tubes and tubes with potentially thrombogenic material) were perfused through their lumen with anticoagulated blood for up to 31 hours. Blood samples were collected at different times from the test system at sites before and after the perfusion of the test catheters. The hemoglobin concentration, erythrocyte, leukocyte and thrombocyte counts and markers for thrombin activation (thrombin-antithrombin III-complex, F1 + 2)-prothrombin fragments) and for hyperfibrinolysis (d-dimers) were determined. No thrombin activation or signs of hyperfibrinolysis were detected in any material tested. Polyethylene tubes were found to cause hemolysis, as shown by a decrease in hemoglobin content from 15 g% to 4.5 g%. Tecothane tubes with and without silver did not induce hemolysis.
Infection 1999
PMID:Thrombogenicity testing of central venous catheters in vitro. 1037 40


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