The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Ingo Fusgen - One of the best experts on this subject based on the ideXlab platform.
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prospective randomized double blind study of the wound debriding effects of collagenase and Fibrinolysin deoxyribonuclease in pressure ulcers
Age and Ageing, 2002Co-Authors: Rupert Pullen, Peter Volkers, Rudiger Popp, Ingo FusgenAbstract:Background: proteolytic enzymes such as collagenase, Fibrinolysin and deoxyribonuclease are used for debriding purulent or fibrinous pressure ulcers. Objective: to test the hypothesis that collagenase debrides necrotic pressure ulcers more effectively than Fibrinolysin/ deoxyribonuclease. Methods: we enrolled 135 elderly patients with pressure ulcers in a randomized, prospective double-blind trial. Patients were treated until complete wound debridement or for a maximum of 4 weeks with twice-daily applications of collagenase or Fibrinolysin/deoxyribonuclease. The primary endpoint was percentage change in the yellow or black wound surface. Secondary endpoints were wound environment, margins, depth, pocketing, area and healing. Assessment was by two independent dermatologists who were unaware of the treatment administered and evaluated results from photographs taken at the beginning and end of treatment. Results: on intention-to-treat analysis, collagenase gave slightly better results with regard to the primary endpoint in the 121 assessable patients, but this difference was not statistically significant (P=0.115). Additional efficacy measures did not show any statistically significant difference between the groups. Conclusion: there was no evidence of a difference between collagenase and Fibrinolysin/deoxyribonuclease in the debridement of pressure ulcers.
Wiete Westerhof - One of the best experts on this subject based on the ideXlab platform.
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quantitative and objective evaluation of wound debriding properties of collagenase and Fibrinolysin desoxyribonuclease in a necrotic ulcer animal model
Archives of Dermatological Research, 1998Co-Authors: Jan R. Mekkes, James E Zeegelaar, Wiete WesterhofAbstract:Proteolytic enzymes have been used for wound debridement for many years. The two enzymes most widely used in Europe are Fibrinolysin/desoxyribonuclease and collagenase. Despite their frequent use, very few placebo-controlled studies comparing the enzymes with vehiculum only, or with each other, are available. In a specially developed necrotic ulcer animal model, combined with a computer image analysis technique to measure necrotic and total wound surface areas quantitatively, we assessed the wound-cleansing properties of Fibrinolysin/DNase oleogel, collagenase ointment, saline-soaked gauze control treatment, and new galenic formulations of collagenase, including placebos. The average relative area of necrotic tissue present in the wound after 1 week was 31% for collagenase ointment and 56% for Fibrinolysin/DNAse oleogel (P = 0.0037). Collagenase gel was significantly (P = 0.0007) better in removing necrosis than placebo (gel only). Fibrinolysin/DNAse was not significantly more effective than the three placebo or control treatments (placebo film, placebo gel, saline-soaked gauzes). We conclude that collagenase is a suitable enzyme for wound debridement, but we were not able to detect clinical efficacy of Fibrinolysin/DNAse in this model.
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in vitro tissue digesting properties of krill enzymes compared with Fibrinolysin dnase papain and placebo
The International Journal of Biochemistry & Cell Biology, 1997Co-Authors: Jan R. Mekkes, Arthur Kammeyer, I Le C Poole, Wiete WesterhofAbstract:Abstract Wound debridement, the removal of necrotic tissue, can be achieved with proteolytic enzymes. Recently, a new multi-enzyme preparation, krill enzyme, isolated from Antarctic shrimp-like organisms (Euphausia superba), was reported to possess powerful proteolytic activity towards protein substrates. In this paper, we study the in vitro digestive properties of krill enzymes towards whole tissue, compared with placebo, papain, and Fibrinolysin/DNAse. Freshly obtained skin specimens were exposed for 3 days to krill enzymes (3; 0.6 and 0.06 U/ml), papain (120; 60; 6 and 0.6 U/ml), Fibrinolysin/DNAse (2.5/1500 E and 1/600 E), and phosphate-buffered saline control solution. Tissue digestion was estimated by measuring wet wt, dry wt, and histological examination. After 72 hr of exposure to 3 U/ml krill enzymes, the dry wt of the specimens was reduced to 2.7% ± 1.9 (SEM, n = 5), compared with 31.0% ± 2.7 for placebo, 25.7% ± 2.5 for 120 U/ml papain, and 24.5% ± 3.3 for 2.5/1500 E/ml Fibrinolysin/DNAse. The differences between krill enzymes and Fibrinolysin/DNAse, papain, and control solution were statistically significant (p
Michael E. Nesheim - One of the best experts on this subject based on the ideXlab platform.
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Thrombin-activable fibrinolysis inhibitor zymogen does not play a significant role in the attenuation of fibrinolysis.
Journal of Biological Chemistry, 2008Co-Authors: Jonathan H. Foley, Paula Kim, Michael E. NesheimAbstract:Activated thrombin-activable fibrinolysis inhibitor (TAFIa) plays a significant role in the prolongation of fibrinolysis. During fibrinolysis, plasminogen is activated to plasmin, which lyses a clot by cleaving fibrin after selected arginine and lysine residues. TAFIa attenuates fibrinolysis by removing the exposed C-terminal lysine residues. It was recently reported that TAFI zymogen possesses sufficient carboxypeptidase activity to attenuate fibrinolysis through a mechanism similar to TAFIa. Here, we show with a recently developed TAFIa assay that when thrombin is used to clot TAFI-deficient plasma supplemented with TAFI, there is some TAFI activation. The extent of activation was dependent upon the concentration of zymogen present in the plasma, and lysis times were prolonged by TAFIa in a concentration-dependent manner. Potato tuber carboxypeptidase inhibitor, an inhibitor of TAFIa but not TAFI, abolished the prolongation of lysis in TAFI-deficient plasma supplemented with TAFI zymogen. In addition, TAFIa but not TAFI catalyzed release of plasminogen bound to soluble fibrin degradation products. The data presented confirm that TAFI zymogen is effective in cleaving a small substrate but does not play a role in the attenuation of fibrinolysis because of its inability to cleave plasmin-modified fibrin degradation products.
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A Study of the Mechanism of Inhibition of Fibrinolysis by Activated Thrombin-activable Fibrinolysis Inhibitor
Journal of Biological Chemistry, 1998Co-Authors: Wei Wang, Michael B. Boffa, Laszlo Bajzar, John Walker, Michael E. NesheimAbstract:Abstract TAFI (thrombin-activable fibrinolysis inhibitor) is a recently described plasma zymogen that, when exposed to the thrombin-thrombomodulin complex, is converted by proteolysis at Arg92 to a basic carboxypeptidase that inhibits fibrinolysis (TAFIa). The studies described here were undertaken to elucidate the molecular basis for the inhibition of fibrinolysis. When TAFIa is included in a clot undergoing fibrinolysis induced by tissue plasminogen activator and plasminogen, the time to achieve lysis is prolonged, and free arginine and lysine are released over time. In addition, TAFIa prevents a 2.5-fold increase in the rate constant for plasminogen activation which occurs when fibrin is modified by plasmin in the early course of fibrin degradation. The effect is specific for the Glu- form of plasminogen. TAFIa prevents or at least attenuates positive feedback expressed through Lys-plasminogen formation during the process of fibrinolysis initiated by tissue plasminogen activator and plasminogen. TAFIa also inhibits plasmin activity in a clot and prolongs fibrinolysis initiated with plasmin. We conclude that TAFIa suppresses fibrinolysis by removing COOH-terminal lysine and arginine residues from fibrin, thereby reducing its cofactor functions in both plasminogen activation and the positive feedback conversion of Glu-plasminogen to Lys-plasminogen. At relatively elevated concentrations, it also directly inhibits plasmin.
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thrombin thrombomodulin and tafi in the molecular link between coagulation and fibrinolysis
Thrombosis and Haemostasis, 1997Co-Authors: Michael E. Nesheim, Wei Wang, Michael B. Boffa, Mariko Nagashima, John Morser, Laszlo BajzarAbstract:Abstract The thrombin thrombomodulin dependent activation of the plasma protein TAFI (Thrombin Activatable Fibrinolysis Inhibitor) and Subsequent Inhibition of Fibrinolysis by the TAFIa is described. Work to date indicates that TAFIa is a carboxypeptidase B enzyme that suppress fibrinolysis most likely by down regulating the cofactor functions of partially degraded fibrin. The existence of TAFI provides the explanation for the apparent profibrinolytic effect of activated protein C. and implies the existence of an explicit molecular connection between the blood coagulation of fibrinolytic cascades that is expressed through the thrombin thrombomodulin dependent activation of TAFI. Thus, thrombin generation can, in principle, result in the suppression of fibrinolysis.
Jan R. Mekkes - One of the best experts on this subject based on the ideXlab platform.
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quantitative and objective evaluation of wound debriding properties of collagenase and Fibrinolysin desoxyribonuclease in a necrotic ulcer animal model
Archives of Dermatological Research, 1998Co-Authors: Jan R. Mekkes, James E Zeegelaar, Wiete WesterhofAbstract:Proteolytic enzymes have been used for wound debridement for many years. The two enzymes most widely used in Europe are Fibrinolysin/desoxyribonuclease and collagenase. Despite their frequent use, very few placebo-controlled studies comparing the enzymes with vehiculum only, or with each other, are available. In a specially developed necrotic ulcer animal model, combined with a computer image analysis technique to measure necrotic and total wound surface areas quantitatively, we assessed the wound-cleansing properties of Fibrinolysin/DNase oleogel, collagenase ointment, saline-soaked gauze control treatment, and new galenic formulations of collagenase, including placebos. The average relative area of necrotic tissue present in the wound after 1 week was 31% for collagenase ointment and 56% for Fibrinolysin/DNAse oleogel (P = 0.0037). Collagenase gel was significantly (P = 0.0007) better in removing necrosis than placebo (gel only). Fibrinolysin/DNAse was not significantly more effective than the three placebo or control treatments (placebo film, placebo gel, saline-soaked gauzes). We conclude that collagenase is a suitable enzyme for wound debridement, but we were not able to detect clinical efficacy of Fibrinolysin/DNAse in this model.
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in vitro tissue digesting properties of krill enzymes compared with Fibrinolysin dnase papain and placebo
The International Journal of Biochemistry & Cell Biology, 1997Co-Authors: Jan R. Mekkes, Arthur Kammeyer, I Le C Poole, Wiete WesterhofAbstract:Abstract Wound debridement, the removal of necrotic tissue, can be achieved with proteolytic enzymes. Recently, a new multi-enzyme preparation, krill enzyme, isolated from Antarctic shrimp-like organisms (Euphausia superba), was reported to possess powerful proteolytic activity towards protein substrates. In this paper, we study the in vitro digestive properties of krill enzymes towards whole tissue, compared with placebo, papain, and Fibrinolysin/DNAse. Freshly obtained skin specimens were exposed for 3 days to krill enzymes (3; 0.6 and 0.06 U/ml), papain (120; 60; 6 and 0.6 U/ml), Fibrinolysin/DNAse (2.5/1500 E and 1/600 E), and phosphate-buffered saline control solution. Tissue digestion was estimated by measuring wet wt, dry wt, and histological examination. After 72 hr of exposure to 3 U/ml krill enzymes, the dry wt of the specimens was reduced to 2.7% ± 1.9 (SEM, n = 5), compared with 31.0% ± 2.7 for placebo, 25.7% ± 2.5 for 120 U/ml papain, and 24.5% ± 3.3 for 2.5/1500 E/ml Fibrinolysin/DNAse. The differences between krill enzymes and Fibrinolysin/DNAse, papain, and control solution were statistically significant (p
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in vitro tissue digesting properties of krill enzymes compared with Fibrinolysin dnase papain and placebo
The International Journal of Biochemistry & Cell Biology, 1997Co-Authors: Jan R. Mekkes, Arthur Kammeyer, I Le C Poole, P K Das, W WesterhofAbstract:Wound debridement, the removal of necrotic tissue, can be achieved with proteolytic enzymes. Recently, a new multi-enzyme preparation, krill enzyme, isolated from Antarctic shrimp-like organisms (Euphausia superba), was reported to possess powerful proteolytic activity towards protein substrates. In this paper, we study the in vitro digestive properties of krill enzymes towards whole tissue, compared with placebo, papain, and Fibrinolysin/DNAse. Freshly obtained skin specimens were exposed for 3 days to krill enzymes (3; 0.6 and 0.06 U/ml), papain (120; 60; 6 and 0.6 U/ml), Fibrinolysin/DNAse (2.5/1500 E and 1/600 E), and phosphate-buffered saline control solution. Tissue digestion was estimated by measuring wet wt, dry wt, and histological examination. After 72 hr of exposure to 3 U/ml krill enzymes, the dry wt of the specimens was reduced to 2.7% +/- 1.9 (SEM, n = 5), compared with 31.0% +/- 2.7 for placebo, 25.7% +/- 2.5 for 120 U/ml papain, and 24.5% +/- 3.3 for 2.5/1500 E/ml Fibrinolysin/DNAse. The differences between krill enzymes and Fibrinolysin/DNAse, papain, and control solution were statistically significant (p < 0.007). These data suggest that krill enzymes are more active than other commonly available proteolytic agents used for wound debridement.
Laszlo Bajzar - One of the best experts on this subject based on the ideXlab platform.
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A Study of the Mechanism of Inhibition of Fibrinolysis by Activated Thrombin-activable Fibrinolysis Inhibitor
Journal of Biological Chemistry, 1998Co-Authors: Wei Wang, Michael B. Boffa, Laszlo Bajzar, John Walker, Michael E. NesheimAbstract:Abstract TAFI (thrombin-activable fibrinolysis inhibitor) is a recently described plasma zymogen that, when exposed to the thrombin-thrombomodulin complex, is converted by proteolysis at Arg92 to a basic carboxypeptidase that inhibits fibrinolysis (TAFIa). The studies described here were undertaken to elucidate the molecular basis for the inhibition of fibrinolysis. When TAFIa is included in a clot undergoing fibrinolysis induced by tissue plasminogen activator and plasminogen, the time to achieve lysis is prolonged, and free arginine and lysine are released over time. In addition, TAFIa prevents a 2.5-fold increase in the rate constant for plasminogen activation which occurs when fibrin is modified by plasmin in the early course of fibrin degradation. The effect is specific for the Glu- form of plasminogen. TAFIa prevents or at least attenuates positive feedback expressed through Lys-plasminogen formation during the process of fibrinolysis initiated by tissue plasminogen activator and plasminogen. TAFIa also inhibits plasmin activity in a clot and prolongs fibrinolysis initiated with plasmin. We conclude that TAFIa suppresses fibrinolysis by removing COOH-terminal lysine and arginine residues from fibrin, thereby reducing its cofactor functions in both plasminogen activation and the positive feedback conversion of Glu-plasminogen to Lys-plasminogen. At relatively elevated concentrations, it also directly inhibits plasmin.
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thrombin thrombomodulin and tafi in the molecular link between coagulation and fibrinolysis
Thrombosis and Haemostasis, 1997Co-Authors: Michael E. Nesheim, Wei Wang, Michael B. Boffa, Mariko Nagashima, John Morser, Laszlo BajzarAbstract:Abstract The thrombin thrombomodulin dependent activation of the plasma protein TAFI (Thrombin Activatable Fibrinolysis Inhibitor) and Subsequent Inhibition of Fibrinolysis by the TAFIa is described. Work to date indicates that TAFIa is a carboxypeptidase B enzyme that suppress fibrinolysis most likely by down regulating the cofactor functions of partially degraded fibrin. The existence of TAFI provides the explanation for the apparent profibrinolytic effect of activated protein C. and implies the existence of an explicit molecular connection between the blood coagulation of fibrinolytic cascades that is expressed through the thrombin thrombomodulin dependent activation of TAFI. Thus, thrombin generation can, in principle, result in the suppression of fibrinolysis.