The Experts below are selected from a list of 531 Experts worldwide ranked by ideXlab platform
Stefan Jockenhoevel - One of the best experts on this subject based on the ideXlab platform.
-
Tranexamic Acid—An Alternative to Aprotinin in Fibrin-Based Cardiovascular Tissue Engineering
2015Co-Authors: Auc Eva Cholewinski, Maren Dietrich, Thomas C Flanagan, Stefan Jockenhoevel, Thomas Schmitz-rode, Ph. DAbstract:Recent clinical trials have led to the worldwide suspension of aprotinin, the most commonly used Antifibrinolytic Agent in fibrin-based tissue engineering. For future clinical applications of fibrin-based scaffolds, a suitable, alternative fibrinolysis inhibitor must be identified. The present study aimed to evaluate tranexamic acid (trans-4-aminomethyl-cyclohexane-1-carboxylic acid [t-AMCA]) as an alternative fibrinolysis inhibitor to aprotinin for cardiovascular tissue engineering applications. The effects of various concentrations of t-AMCA (30–160 mg=mL) and aprotinin on fibrin gel-lysis were spectrophotometrically quantified in vitro. Cytotoxic effects of t-AMCA and aprotinin on carotid artery–derived cells, in addition to their influence on fibrin gel mechanical strength, were examined. Further, the influence of t-AMCA versus aprotinin on three-dimensional fibrin-based constructs was analyzed using light microscopy, scanning electron microscopy, and transmission electron microscopy. The results demonstrated that neither t-AMCA (30–160 mg=mL) nor aprotinin elicited cytotoxic effects on cultured cells. Although aprotinin showed reduced fibrinolysis in the presence of plasmin compared to t-AMCA, no significant difference was obtained under standard culture conditions. Additionally, t-AMCA had no negative influence on the mechanical stability of fibrin gels, which also demonstrated excellent cell morphology, tissue development, and ultrastructure. The results from the present study demonstrate that t-AMCA may be a suitable alternative to aprotinin for controlling the in vitro degradation rate of fibrin-based tissue-engineered constructs
-
tranexamic acid an alternative to aprotinin in fibrin based cardiovascular tissue engineering
Tissue Engineering Part A, 2009Co-Authors: Eva Cholewinski, Maren Dietrich, Thomas C Flanagan, Thomas Schmitzrode, Stefan JockenhoevelAbstract:Recent clinical trials have led to the worldwide suspension of aprotinin, the most commonly used Antifibrinolytic Agent in fibrin-based tissue engineering. For future clinical applications of fibrin-based scaffolds, a suitable, alternative fibrinolysis inhibitor must be identified. The present study aimed to evaluate tranexamic acid (trans-4-aminomethyl-cyclohexane-1-carboxylic acid [t-AMCA]) as an alternative fibrinolysis inhibitor to aprotinin for cardiovascular tissue engineering applications. The effects of various concentrations of t-AMCA (30-160 microg/mL) and aprotinin on fibrin gel-lysis were spectrophotometrically quantified in vitro. Cytotoxic effects of t-AMCA and aprotinin on carotid artery-derived cells, in addition to their influence on fibrin gel mechanical strength, were examined. Further, the influence of t-AMCA versus aprotinin on three-dimensional fibrin-based constructs was analyzed using light microscopy, scanning electron microscopy, and transmission electron microscopy. The results demonstrated that neither t-AMCA (30-160 microg/mL) nor aprotinin elicited cytotoxic effects on cultured cells. Although aprotinin showed reduced fibrinolysis in the presence of plasmin compared to t-AMCA, no significant difference was obtained under standard culture conditions. Additionally, t-AMCA had no negative influence on the mechanical stability of fibrin gels, which also demonstrated excellent cell morphology, tissue development, and ultrastructure. The results from the present study demonstrate that t-AMCA may be a suitable alternative to aprotinin for controlling the in vitro degradation rate of fibrin-based tissue-engineered constructs.
Umesh R. Desai - One of the best experts on this subject based on the ideXlab platform.
-
potent selective allosteric inhibition of human plasmin by sulfated non saccharide glycosaminoglycan mimetics
Journal of Medicinal Chemistry, 2017Co-Authors: Daniel K. Afosah, Nehru Viji Sankaranarayanan, Rami A Alhorani, Umesh R. DesaiAbstract:Although plasmin inhibitors could be used in multiple disorders, their use has been restricted to preventing blood loss in hemostatic dysregulation because of poor efficacy and adverse effects of current Agents. We reasoned that a new class of direct inhibitors that offer better efficacy, selectivity, and safety could be discovered by exploiting allosterism in plasmin, a protease homologous to other allosteric serine proteases. We report on the synthesis, biological activity, and mechanism of action of a group of small molecules, called non-saccharide glycosaminoglycan mimetics (NSGMs), as direct allosteric plasmin inhibitors. Our results show that distinct NSGMs selectively inhibit human full-length plasmin. The molecule inhibited clot lysis, alluding to its promise as an allosteric regulator of plasmin. We show that direct allosteric inhibition of plasmin could led to new Antifibrinolytic Agent(s) that may exhibit better efficacy, potency, selectivity, and safety in comparison to current therapy.
-
Potent, Selective, Allosteric Inhibition of Human Plasmin by Sulfated Non-Saccharide Glycosaminoglycan Mimetics
2016Co-Authors: Daniel K. Afosah, Rami A. Al-horani, Nehru Viji Sankaranarayanan, Umesh R. DesaiAbstract:Although plasmin inhibitors could be used in multiple disorders, their use has been restricted to preventing blood loss in hemostatic dysregulation because of poor efficacy and adverse effects of current Agents. We reasoned that a new class of direct inhibitors that offer better efficacy, selectivity, and safety could be discovered by exploiting allosterism in plasmin, a protease homologous to other allosteric serine proteases. We report on the synthesis, biological activity, and mechanism of action of a group of small molecules, called non-saccharide glycosaminoglycan mimetics (NSGMs), as direct allosteric plasmin inhibitors. Our results show that distinct NSGMs selectively inhibit human full-length plasmin. The molecule inhibited clot lysis, alluding to its promise as an allosteric regulator of plasmin. We show that direct allosteric inhibition of plasmin could led to new Antifibrinolytic Agent(s) that may exhibit better efficacy, potency, selectivity, and safety in comparison to current therapy
Eva Cholewinski - One of the best experts on this subject based on the ideXlab platform.
-
tranexamic acid an alternative to aprotinin in fibrin based cardiovascular tissue engineering
Tissue Engineering Part A, 2009Co-Authors: Eva Cholewinski, Maren Dietrich, Thomas C Flanagan, Thomas Schmitzrode, Stefan JockenhoevelAbstract:Recent clinical trials have led to the worldwide suspension of aprotinin, the most commonly used Antifibrinolytic Agent in fibrin-based tissue engineering. For future clinical applications of fibrin-based scaffolds, a suitable, alternative fibrinolysis inhibitor must be identified. The present study aimed to evaluate tranexamic acid (trans-4-aminomethyl-cyclohexane-1-carboxylic acid [t-AMCA]) as an alternative fibrinolysis inhibitor to aprotinin for cardiovascular tissue engineering applications. The effects of various concentrations of t-AMCA (30-160 microg/mL) and aprotinin on fibrin gel-lysis were spectrophotometrically quantified in vitro. Cytotoxic effects of t-AMCA and aprotinin on carotid artery-derived cells, in addition to their influence on fibrin gel mechanical strength, were examined. Further, the influence of t-AMCA versus aprotinin on three-dimensional fibrin-based constructs was analyzed using light microscopy, scanning electron microscopy, and transmission electron microscopy. The results demonstrated that neither t-AMCA (30-160 microg/mL) nor aprotinin elicited cytotoxic effects on cultured cells. Although aprotinin showed reduced fibrinolysis in the presence of plasmin compared to t-AMCA, no significant difference was obtained under standard culture conditions. Additionally, t-AMCA had no negative influence on the mechanical stability of fibrin gels, which also demonstrated excellent cell morphology, tissue development, and ultrastructure. The results from the present study demonstrate that t-AMCA may be a suitable alternative to aprotinin for controlling the in vitro degradation rate of fibrin-based tissue-engineered constructs.
Tami Livnat - One of the best experts on this subject based on the ideXlab platform.
-
single low dose of rfviia combined with Antifibrinolytic Agent is a simple and safe treatment for factor xi deficient patients undergoing surgery
Thrombosis and Haemostasis, 2019Co-Authors: Ophira Salomon, Ivan Budnik, Einat Avishai, Ilia Tamarin, D Bashari, Rima Dardik, Tami LivnatAbstract:Background Factor XI (FXI) deficiency is a rare autosomal bleeding disorder. The rarity of spontaneous bleeding and absence of optimal tools to predict the bleeding risk in FXI-deficient patients hamper the standardization of prophylactic treatment enabling them to undergo major surgeries without blood products. Objectives We explored the effectiveness of a single and very low dose of recombinant factor VIIa (rFVIIa) along with tranexamic acid (TXA) as prophylactic treatment for FXI-deficient patients undergoing various types of surgery at various sites of injury. We studied the potential use of thrombin generation (TG) as a surrogate tool for predicting thrombogenicity. Patients and Methods Our cohort consisted of 10 patients with severe FXI deficiency undergoing 12 interventions. Patients received a single dose of 10 to 15 μg/kg rFVIIa at the end of surgery in addition to TXA initiated 2 hours before surgery at the dose of 4 g/day for 3 to 5 days. TG was tested before and 30 minutes after rFVIIa administration. Results All operations were uneventful and none of the patients bled excessively or required blood products. No thrombotic event was reported, and the postoperative hospitalization duration was comparable to that of patients without bleeding disorders. TG performed at the peak of rFVIIa was below the curve of healthy controls, thus confirming that the administered dose was not thrombogenic. Conclusion A single very low dose of rFVIIa along with TXA is a simple and safe treatment to control hemostasis in severe FXI-deficient patients undergoing diverse type of surgical procedure at various sites.
Thomas C Flanagan - One of the best experts on this subject based on the ideXlab platform.
-
Tranexamic Acid—An Alternative to Aprotinin in Fibrin-Based Cardiovascular Tissue Engineering
2015Co-Authors: Auc Eva Cholewinski, Maren Dietrich, Thomas C Flanagan, Stefan Jockenhoevel, Thomas Schmitz-rode, Ph. DAbstract:Recent clinical trials have led to the worldwide suspension of aprotinin, the most commonly used Antifibrinolytic Agent in fibrin-based tissue engineering. For future clinical applications of fibrin-based scaffolds, a suitable, alternative fibrinolysis inhibitor must be identified. The present study aimed to evaluate tranexamic acid (trans-4-aminomethyl-cyclohexane-1-carboxylic acid [t-AMCA]) as an alternative fibrinolysis inhibitor to aprotinin for cardiovascular tissue engineering applications. The effects of various concentrations of t-AMCA (30–160 mg=mL) and aprotinin on fibrin gel-lysis were spectrophotometrically quantified in vitro. Cytotoxic effects of t-AMCA and aprotinin on carotid artery–derived cells, in addition to their influence on fibrin gel mechanical strength, were examined. Further, the influence of t-AMCA versus aprotinin on three-dimensional fibrin-based constructs was analyzed using light microscopy, scanning electron microscopy, and transmission electron microscopy. The results demonstrated that neither t-AMCA (30–160 mg=mL) nor aprotinin elicited cytotoxic effects on cultured cells. Although aprotinin showed reduced fibrinolysis in the presence of plasmin compared to t-AMCA, no significant difference was obtained under standard culture conditions. Additionally, t-AMCA had no negative influence on the mechanical stability of fibrin gels, which also demonstrated excellent cell morphology, tissue development, and ultrastructure. The results from the present study demonstrate that t-AMCA may be a suitable alternative to aprotinin for controlling the in vitro degradation rate of fibrin-based tissue-engineered constructs
-
tranexamic acid an alternative to aprotinin in fibrin based cardiovascular tissue engineering
Tissue Engineering Part A, 2009Co-Authors: Eva Cholewinski, Maren Dietrich, Thomas C Flanagan, Thomas Schmitzrode, Stefan JockenhoevelAbstract:Recent clinical trials have led to the worldwide suspension of aprotinin, the most commonly used Antifibrinolytic Agent in fibrin-based tissue engineering. For future clinical applications of fibrin-based scaffolds, a suitable, alternative fibrinolysis inhibitor must be identified. The present study aimed to evaluate tranexamic acid (trans-4-aminomethyl-cyclohexane-1-carboxylic acid [t-AMCA]) as an alternative fibrinolysis inhibitor to aprotinin for cardiovascular tissue engineering applications. The effects of various concentrations of t-AMCA (30-160 microg/mL) and aprotinin on fibrin gel-lysis were spectrophotometrically quantified in vitro. Cytotoxic effects of t-AMCA and aprotinin on carotid artery-derived cells, in addition to their influence on fibrin gel mechanical strength, were examined. Further, the influence of t-AMCA versus aprotinin on three-dimensional fibrin-based constructs was analyzed using light microscopy, scanning electron microscopy, and transmission electron microscopy. The results demonstrated that neither t-AMCA (30-160 microg/mL) nor aprotinin elicited cytotoxic effects on cultured cells. Although aprotinin showed reduced fibrinolysis in the presence of plasmin compared to t-AMCA, no significant difference was obtained under standard culture conditions. Additionally, t-AMCA had no negative influence on the mechanical stability of fibrin gels, which also demonstrated excellent cell morphology, tissue development, and ultrastructure. The results from the present study demonstrate that t-AMCA may be a suitable alternative to aprotinin for controlling the in vitro degradation rate of fibrin-based tissue-engineered constructs.