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Zhongguo Yao Li Xue Bao = Acta... Nov 1993Aprotinin inhibited platelet aggregation induced by thrombin (0.25 U.ml-1) with IC50 200 kIU.ml-1, and inhibited the rise of cytosolic free calcium concentration in...
Aprotinin inhibited platelet aggregation induced by thrombin (0.25 U.ml-1) with IC50 200 kIU.ml-1, and inhibited the rise of cytosolic free calcium concentration in platelets stimulated by thrombin (0.1 U.ml-1) in the absence and in the presence of Ca2+ 0.5 mmol.L-1 (IC50 117 and 50 kIU.ml-1, respectively), but had no effect on the amounts of actin and myosin heavy chain associated with cytoskeletons. These suggest that aprotinin is an anti-platelet agent and may exert its action through inhibiting the Ca2+ flux.
Topics: Animals; Aprotinin; Calcium; Cytoskeletal Proteins; Cytosol; Platelet Aggregation; Platelet Aggregation Inhibitors; Swine
PubMed: 7516610
DOI: No ID Found -
Journal of Biomedical Materials... Sep 2016Cell therapy has the potential to treat different pathologies, including myocardial infarctions (heart attacks), although cell engraftment remains elusive with most...
Cell therapy has the potential to treat different pathologies, including myocardial infarctions (heart attacks), although cell engraftment remains elusive with most delivery methods. Biological sutures composed of fibrin have been shown to effectively deliver human mesenchymal stem cell (MSC) to infarcted hearts. However, human MSCs rapidly degrade fibrin making cell seeding and delivery time sensitive. To delay the degradation process, we propose using Aprotinin, a proteolytic enzyme inhibitor that has been shown to slow fibrinolysis. Human MSCs seeded on fibrin sutures and incubated with Aprotinin demonstrated similar cell viability, examined using a LIVE/DEAD stain, to controls. No differences in proliferation, as determined by Ki-67 presence, were observed. Human MSCs incubated in Aprotinin differentiated into adipocytes, osteocytes, and chondrocytes, confirming multipotency. The number of cells adhered to fibrin sutures increased through Aprotinin supplementation at 2, 3, and 5 day time points. Uniaxial tensile testing was used to examine the effect of Aprotinin on suture integrity. Sutures exposed to Aprotinin had higher ultimate tensile strength and modulus when compared to sutures exposed to standard growth media. Fibrin sutures incubated in Aprotinin had larger diameters and less fibrin degradation products compared to the controls, confirming decreased fibrinolysis. These data suggest that Aprotinin can reduce degradation of fibrin sutures without significant effects on MSC function, providing a novel method for extending the implantation window and increasing the number of cells delivered via fibrin sutures. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2271-2279, 2016.
Topics: Aprotinin; Cell Differentiation; Cell Line; Fibrin; Humans; Mesenchymal Stem Cells; Sutures
PubMed: 27101153
DOI: 10.1002/jbm.a.35754 -
British Medical Journal Oct 1971
Topics: Aminocaproates; Aprotinin; Bradykinin; Female; Humans; Pregnancy; Uterine Inertia
PubMed: 5315945
DOI: 10.1136/bmj.4.5782.301 -
British Medical Journal Sep 1971
Topics: Amniotic Fluid; Aprotinin; Female; Fibrin; Humans; Postpartum Hemorrhage; Pregnancy; Uterine Inertia
PubMed: 5315153
DOI: 10.1136/bmj.3.5775.637 -
British Journal of Anaesthesia Aug 1995
Topics: Aprotinin; Hemostatics; Humans; Thrombosis
PubMed: 7577258
DOI: 10.1093/bja/75.2.246 -
Anesthesiology Sep 2002
Topics: Aprotinin; Diatomaceous Earth; Hemostatics; Humans; Kaolin; Thrombelastography
PubMed: 12218558
DOI: 10.1097/00000542-200209000-00049 -
Journal of Thrombosis and Haemostasis :... Oct 2007The serine protease inhibitor aprotinin and plasminogen inhibitor tranexamic acid are used in coronary artery bypass graft (CABG) surgery to reduce bleeding. Clinicians...
BACKGROUND
The serine protease inhibitor aprotinin and plasminogen inhibitor tranexamic acid are used in coronary artery bypass graft (CABG) surgery to reduce bleeding. Clinicians may consider these agents as readily substitutable regarding their pharmacological profiles.
OBJECTIVE
These agents were evaluated in assays of hemostasis to elucidate their underlying mechanism(s) of action.
METHODS
In human plasma, effects on both clot fibrinolysis and coagulation were spectrophotometrically quantified in vitro. Rat-tail bleeding and arteriovenous shunt thrombus formation models were conducted in vivo.
RESULTS
Fibrinolysis was inhibited by aprotinin (IC(50), 0.16 +/- 0.02 micromol L(-1)) and tranexamic acid (IC(50), 24.1 +/-1.1 micromol L(-1)). In vivo, aprotinin dose-dependently reduced rat-tail bleeding time (minimal effective dose, 3 mg kg(-1) bolus plus 6 mg kg(-1 )h(-1) infusion); tranexamic acid reduced bleeding time (minimal effective dose, 100 mg kg(-1) h(-1)). In vitro, coagulation time was doubled by aprotinin at 3.2 +/- 0.2 micromol L(-1), while tranexamic acid showed no effect at concentrations up to 3 mmol L(-1). Aprotinin inhibited thrombus formation in vivo in a dose-dependent manner (minimal effective dose, 3 mg kg(-1) bolus plus 6 mg kg(-1) h(-1) infusion). Conversely, tranexamic acid dose-dependently increased thrombus formation and thrombus weight (minimal effective dose, 100 mg kg(-1 )h(-1) infusion).
CONCLUSIONS
These data show that aprotinin and tranexamic acid have differential effects on hemostasis and are not necessarily substitutable with respect to mechanism of action. Although both agents have been shown to reduce bleeding in patients undergoing CABG, their divergent effects on thrombus formation observed in vitro and in vivo should be critically evaluated clinically.
Topics: Animals; Antifibrinolytic Agents; Aprotinin; Arteriovenous Shunt, Surgical; Blood Coagulation; Dose-Response Relationship, Drug; Fibrinolysis; Hemostatics; Humans; Male; Rats; Rats, Wistar; Thrombosis; Tranexamic Acid
PubMed: 17666018
DOI: 10.1111/j.1538-7836.2007.02717.x -
BMJ (Clinical Research Ed.) Sep 2012To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the suspension of aprotinin from the market in 2008 for safety reasons and its recent reintroduction in Europe and Canada.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
A Cochrane review of antifibrinolytic treatments was chosen as the starting point for this systematic review. Medline, Embase, and the Cochrane register of trials were searched with no date restrictions for observational evidence.
STUDY SELECTION
Propensity matched or adjusted observational studies with two or more of the interventions of interest (aprotinin, tranexamic acid, epsilon-aminocaproic acid, and no treatment) that were carried out in patients undergoing cardiac surgery.
DATA ANALYSIS
Network meta-analysis was used to compare treatments, and odds ratios with 95% credible intervals were estimated. Meta-analyses were carried out for randomised controlled trials alone and for randomised controlled trials with observational studies.
RESULTS
106 randomised controlled trials and 11 observational studies (43,270 patients) were included. Based on the results from analysis of randomised controlled trials, tranexamic acid was associated on average with a reduced risk of death compared with aprotinin (odds ratio 0.64, 95% credible interval 0.41 to 0.99). When observational data were incorporated, comparisons showed an increased risk of mortality with aprotinin on average relative to tranexamic acid (odds ratio 0.71, 95% credible interval 0.50 to 0.98) and epsilon-aminocaproic acid (0.60, 0.43 to 0.87), and an increased risk of renal failure or dysfunction on average relative to all comparators: odds ratio 0.66 (95% credible interval 0.45 to 0.88) compared with no treatment, 0.66 (0.48 to 0.91) versus tranexamic acid, and 0.65 (0.45 to 0.88) versus epsilon-aminocaproic acid.
CONCLUSION
Although meta-analyses of randomised controlled trials were largely inconclusive, inclusion of observational data suggest concerns remain about the safety of aprotinin. Tranexamic and epsilon-aminocaproic acid are effective alternatives that may be safer for patients.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Humans; Myocardial Infarction; Odds Ratio; Postoperative Complications; Renal Insufficiency; Risk; Stroke; Tranexamic Acid
PubMed: 22968722
DOI: 10.1136/bmj.e5798 -
European Journal of Biochemistry Apr 2000Different low molecular mass ligands have been used to identify amyloid deposits. Among these markers, the dyes Thioflavin T and Congo Red interact specifically with the...
Different low molecular mass ligands have been used to identify amyloid deposits. Among these markers, the dyes Thioflavin T and Congo Red interact specifically with the beta-sheet structure arranged in a cross-beta conformation, which is characteristic of amyloid. However, the molecular details of this interaction remain unknown. When labelled with technetium-99m, the proteinase inhibitor aprotinin has been shown to represent a very important radiopharmaceutical agent for in vivo imaging of extra-abdominal deposition of amyloid in amyloidosis of the immunoglobulin type. However, no information is available as to whether aprotinin binds other types of amyloid fibrils and on the nature and characteristics of the interaction. The present work shows aprotinin binding to insulin, transthyretin, beta-amyloid peptide and immunoglobulin synthetic amyloid fibrils by a specific dot-blot ligand-binding assay. Aprotinin did not bind amorphous precipitates and/or the soluble fibril precursors. A Ka of 2.9 microM-1 for the binding of aprotinin to insulin amyloid fibrils was determined by Scatchard analysis. In competition experiments, analogues such as an aprotinin variant, a spermadhesin and the soybean trypsin inhibitor were tested and results suggest that both aprotinin and the spermadhesin interact with amyloid fibrils through pairing of beta-sheets of the ligands with exposed structures of the same type at the surface of amyloid deposits. An electrostatic component may also be involved in the binding of aprotinin to amyloid fibrils because important differences in binding constants are observed when substitutions V15L17E52 are introduced in aprotinin; on the other hand beta-sheet containing acidic proteins, such as the soybean trypsin inhibitor, are unable to bind amyloid fibrils.
Topics: Amyloid; Animals; Aprotinin; Binding, Competitive; Biomarkers; Biotinylation; Glycoproteins; Insulin; Iodine Radioisotopes; Microfibrils; Models, Molecular; Mutation; Prealbumin; Protein Binding; Protein Structure, Secondary; Seminal Vesicle Secretory Proteins
PubMed: 10759855
DOI: 10.1046/j.1432-1327.2000.01237.x -
The Journal of Thoracic and... Oct 2009Use of aprotinin has been suspended in cardiac surgery since recent studies reported its risks associated with mortality and other adverse events. This study was to... (Comparative Study)
Comparative Study
OBJECTIVE
Use of aprotinin has been suspended in cardiac surgery since recent studies reported its risks associated with mortality and other adverse events. This study was to investigate the safety and efficacy of aprotinin through a comparison before and after aprotinin was suspended in cardiac surgery.
METHODS
We designed a case-control study in two groups of patients who underwent cardiac surgery just before and after aprotinin was suspended in China. The aprotinin group (n = 1699) was defined as operations performed from June 19, 2007, to December 18, 2007, when aprotinin was used in all the patients. The control group (n = 2225) was defined as operations performed from December 19, 2007, to June 18, 2008, when aprotinin was not used. We compared early postoperative outcomes between the two groups.
RESULTS
The aprotinin group had less postoperative blood loss, transfusion requirement, and reoperation for bleeding. Application of aprotinin did not increase the risk of in-hospital mortality (0.5% vs 1.0%; P = .08) and other major adverse outcome events, including renal, cardiac, neurologic, and pulmonary complications. The aprotinin group had a shorter mechanical ventilation time (P = .04), a lower rate of delayed mechanical ventilation time (P = .04), and a higher arterial oxygen tension/inspired oxygen fraction ratio in arterial blood gas analysis (P < .001). Multivariable logistic regression analysis confirmed findings from univariate analysis. After propensity adjustment for the baseline characteristics, we obtained similar results.
CONCLUSIONS
Use of aprotinin in cardiac surgery could reduce blood loss and transfusion requirement significantly and showed a protective effect on the lungs, but it did not increase the risk of mortality or major complications.
Topics: Aged; Aprotinin; Blood Loss, Surgical; Blood Transfusion; Cardiac Surgical Procedures; Female; Hemostatics; Hospital Mortality; Humans; Male; Middle Aged; Postoperative Care; Postoperative Complications; Reoperation; Respiration, Artificial; Serine Proteinase Inhibitors
PubMed: 19660368
DOI: 10.1016/j.jtcvs.2009.03.021