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Seminars in Thrombosis and Hemostasis Apr 1987
Review
Topics: Amino Acid Sequence; Animals; Chemical Phenomena; Chemistry, Physical; Coronary Thrombosis; Dogs; Drug Synergism; Enzyme Activation; Fibrinolytic Agents; Humans; Kinetics; Myocardial Infarction; Plasminogen; Plasminogen Activators; Protein Conformation; Recombinant Proteins; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator
PubMed: 3114883
DOI: 10.1055/s-2007-1003486 -
European Heart Journal Dec 1997Thrombolysis has become an accepted form of therapy for acute myocardial infarction. As demonstrated in the Global Utilization of Streptokinase and t-PA for Occluded... (Review)
Review
Thrombolysis has become an accepted form of therapy for acute myocardial infarction. As demonstrated in the Global Utilization of Streptokinase and t-PA for Occluded Arteries trial, early, complete and sustained patency of the infarct-related coronary artery is correlated with reduced mortality. However, current thrombolytic regimens are able to achieve such patency within 90 min in only 81% of cases. To improve the risk/benefit ratio of thrombolytic therapy, newer agents such as reteplase have been developed to establish more rapid, more complete and more stable coronary artery patency, thus reducing mortality. This report summarizes the pharmacological properties of reteplase. It also summarizes the findings from various animal and clinical studies in which reteplase was compared with alteplase and streptokinase and the findings from animal and clinical studies evaluating infusion, single-bolus, double-bolus, doses of reteplase.
Topics: Amino Acid Sequence; Animals; Clinical Trials as Topic; Fibrinolytic Agents; Humans; Plasminogen Activators; Recombinant Proteins; Tissue Plasminogen Activator
PubMed: 9447336
DOI: 10.1093/eurheartj/18.suppl_f.17 -
The Journal of Pharmacy and Pharmacology Aug 2012This review should give an overview about the natural human plasminogen activators and their various modified variants as well as similar substances isolated from... (Review)
Review
OBJECTIVES
This review should give an overview about the natural human plasminogen activators and their various modified variants as well as similar substances isolated from animals, microorganisms and plants. When a blood clot is formed in a blood vessel, it avoids the oxygen supply of the surrounding tissue. A fast fibrinolytic therapy should redissolve the blood vessel and reduce the degradation of the tissue. All proteases that are part of the human blood coagulation and fibrinolytic system belong to the serine protease family. t-PA (tissue plasminogen activator) and u-PA (urokinase plasminogen activator) are the naturally occurring fibrinolytic agents that are also used in therapy.
KEY FINDINGS
Despite many years of research, t-PA is still the gold standard in fibrinolytic therapy. But it has to be given as an infusion, which needs time. Modified fibrinolytic substances are, were, or perhaps will be in the market. They have different advantages over t-PA, but often the disadvantages predominate.
CONCLUSION
Many substances have been developed but an optimal fibrinolytic agent combined with a simple administration is not in therapeutic use to date.
Topics: Animals; Blood Coagulation; Fibrinolysis; Fibrinolytic Agents; Humans; Plasminogen Activators; Serine Proteases; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator
PubMed: 22775207
DOI: 10.1111/j.2042-7158.2012.01457.x -
Zhonghua Nan Ke Xue = National Journal... Apr 2003Plasminogen activator(PA) and plasminogen activator inhibitor(PAI) are involved in many physiological or pathological events. The Sertoli cells, the important elements... (Review)
Review
Plasminogen activator(PA) and plasminogen activator inhibitor(PAI) are involved in many physiological or pathological events. The Sertoli cells, the important elements within the seminiferous epithelium, are thought to play a key role in spermatogenesis. The Sertoli cells secrete PA and PAI. The levels of them are modulated by hormonal and cell-mediated influences. They play a fundamental role in the maintenance of spermatogenesis, sperm motility and fertilization.
Topics: Humans; Male; Plasminogen Activators; Plasminogen Inactivators; Sertoli Cells; Testis
PubMed: 12749136
DOI: No ID Found -
The Journal of Biological Chemistry Jul 1981The plasminogen activator secreted by a cultured human melanoma cell line was purified and compared with urokinase and with tissue plasminogen activator from human...
The plasminogen activator secreted by a cultured human melanoma cell line was purified and compared with urokinase and with tissue plasminogen activator from human uterus. The purification procedure consisted of chromatography on zinc chelate-agarose, concanavalin A-agarose, and Sephadex G-150 in the presence of 0.01% (v/v) Tween 80. The purified material was obtained from the culture medium with a yield of 46% and a purification factor of 263. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed one main band with a molecular weight of about 72,000, and in the presence of reducing agents, two bands of 33,000 and 39,000. Addition of the protease inhibitor Aprotinin to the culture media and column buffers yielded a one-chain plasminogen activator with a molecular weight of about 72,000. One molecule of activator reacted with about one molecular of [3H]diisopropylfluorophosphate. The melanoma plasminogen activator and the uterine tissue plasminogen activator appeared to be very similar on dodecyl sulfate-polyacrylamide gel electrophoresis, amino acid analysis, and amidolytic properties. Both activators bound to fibrin clots, while urokinase did not. In immunodiffusion, as well as in quenching experiments of the fibrinolytic activities, the melanoma plasminogen activator appeared to be immunologically identical with the uterine tissue plasminogen activator, but unrelated to urokinase. All these findings indicate that the plasminogen activator secreted by human melanoma cells in culture is very similar to, or identical with, the plasminogen activator found in normal tissue, but different from urokinase.
Topics: Amino Acids; Cell Line; Female; Fibrinolysis; Humans; Immune Sera; Immunodiffusion; Kinetics; Melanoma; Plasminogen Activators; Uterus
PubMed: 6787058
DOI: No ID Found -
Advances in Clinical Chemistry 2004
Review
Topics: Clinical Chemistry Tests; Humans; Plasminogen Activators; Plasminogen Inactivators
PubMed: 15521190
DOI: 10.1016/s0065-2423(04)38004-2 -
Seminars in Thrombosis and Hemostasis Jan 1984
Topics: Amino Acid Sequence; Animals; Chemical Phenomena; Chemistry; Fibrin; Humans; Plasminogen Activators; Plasminogen Inactivators; Thrombosis
PubMed: 6422555
DOI: 10.1055/s-2007-1004403 -
Cell Feb 1988We have previously shown that inhibition of uPA activity of a human tumor-HEp3-results in a drastic reduction of its metastasis in the chick embryo. Using...
We have previously shown that inhibition of uPA activity of a human tumor-HEp3-results in a drastic reduction of its metastasis in the chick embryo. Using 125IUdR-labeled tumor cells, we have now studied the role of uPA in individual steps of tumor metastasis. We found that, 48 hr after inoculation of tumor cells on the CAM, the organs of the embryos, inoculated with cells in which uPA was inhibited, contained 4-fold less cells than the controls. Neither the initial advance of the tumor mass into the CAM nor the process of extravasation was affected by the inhibition of tumor uPA. However, the infiltration of the CAM mesenchyme by individual tumor cells was blocked when tumor uPA activity or production was inhibited. In addition, indirect evidence implicated uPA as an essential factor in the tumor cell intravasation.
Topics: Allantois; Animals; Catalysis; Chick Embryo; Chorion; Dimethyl Sulfoxide; Humans; Immunoglobulin G; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Plasminogen Activators; Plasminogen Inactivators; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator
PubMed: 3125981
DOI: 10.1016/s0092-8674(88)80025-4 -
The Journal of Laboratory and Clinical... Dec 1982Dilute clot lysis was assayed by release of soluble 125I fibrin degradation products from dPPP clots containing varying amounts of plasminogen activator and platelets....
Dilute clot lysis was assayed by release of soluble 125I fibrin degradation products from dPPP clots containing varying amounts of plasminogen activator and platelets. Plasminogen activator in the absence of platelets gave an approximately linear rate of lysis, with a rate proportional to its concentration. Addition of platelets to achieve normal clot retraction had little effect on the lysis rate in the absence of plasminogen activator or in the presence of very high plasminogen activator levels. However, with intermediate plasminogen activator levels, platelet-mediated clot retraction was associated with an accelerated rate of clot lysis when retraction reached 75% to 90%. The length of the lag phase before the start of the accelerated phase varied with the number of platelets and rate of clot retraction. The interaction of clot retraction and lysis was further explored in selected patients to determine (1) whether the contributions of platelet and plasma factors in these cases was similar to those seen in our studies of reconstituted plasma and (2) whether our experience with reconstituted systems could be used in the study of disorders of fibrinolysis involving platelets and fibrinolytic enzymes.
Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Humans; Liver Cirrhosis; Plasminogen; Plasminogen Activators
PubMed: 6890569
DOI: No ID Found -
The British Journal of Dermatology Aug 1986A plasminogen activator (PA), Mr 72,000, was detected in conditioned medium from human melanocyte cultures by fibrin autography. The electrophoretic mobility was...
A plasminogen activator (PA), Mr 72,000, was detected in conditioned medium from human melanocyte cultures by fibrin autography. The electrophoretic mobility was identical to that of tissue PA produced by Bowes melanoma cells. PA activity in human melanocyte culture medium was inhibited by anti-tissue PA IgG, but not by anti-urokinase IgG. Our results are the first to show that normal human melanocytes in culture secrete tissue plasminogen activator.
Topics: Cells, Cultured; Humans; Immunoglobulin G; Infant, Newborn; Male; Melanocytes; Molecular Weight; Plasminogen Activators; Plasminogen Inactivators; Urokinase-Type Plasminogen Activator
PubMed: 3091061
DOI: 10.1111/j.1365-2133.1986.tb05719.x