Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMINOCAPROIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,639 records · Page 91Linked to original sources
PubMedDate not supplied

[Heparin-aspirin complex, its physico-chemical and physiologic properties].

A method is developed for isolation of fibrinolytic and anticoagulant complex heparin-aspirin. The complex possessed the highest activity when the ratio of heparin to aspirin was 10 : 1. In vitro and in vivo the complex obtained showed high anticoagulant and fibrinolytic activity with respect to unstabilized fibrin both in absence and in presence of epsilon-aminocaproic acid as well as it had the thrombolytic effect on the fresh thrombus. The total fibrinolytic activity, nonenzymatic fibrinolysis and the anticoagulation activity in blood plasma were increased after chronic administration per os and after repeated intramuscular administration of the complex. The most distinct increase in fibrinolytic properties of blood occurred after intravenous administration of the heparin-aspirin complex.

Animals↗
PubMed1995

Fluorogenic fibrinogen and fibrin facilitate macromolecular assembly and dynamic assay of picomolar levels of plasminogen activators under well mixed conditions.

Fibrinogen labeled with fluorescein isothiocyanate (FITC) was tested for its ability to serve as a template for macromolecular assembly as well as to provide a fluorogenic signal to allow continuous monitoring of plasminogen activation and fibrinolysis. As dilute solutions of FITC-fibrinogen or FITC-fibrin fiber suspension were degraded during lysis, release of fluorescent fragments abolished proximity-based quenching and resulted in a 2.0- or 3.6-fold increase in fluorescence intensity, respectively. Addition of plasmin at a final concentration of 10 pM to FITC-fibrinogen (10 nM) produced a detectable level of fluorescence dequenching. The assay had sufficient sensitivity to detect plasmin activity in the presence of excess antiplasmin activity, indicating the dissociation of a reversible antiplasmin-plasmin complex. The detection limit of the reaction assay was 20 pM and 200 pM of recombinant tPA and urokinase, using 10 nM FITC-fibrin and 10 nM and 5 nM plasminogen, respectively. The 10-fold greater sensitivity of the assay for tPA was likely due to the molecular assembly of tPA and plasminogen on the FITC-fibrin. Addition of thrombin (1 U/ml) and plasmin (0.1 nM) to 10 nM FITC-fibrinogen produced fluorescence quenching at first due to fibrinogen polymerization followed by dequenching due to fibrinolysis. Addition of 10 mM epsilon-aminocaproic acid to mixtures of thrombin and plasmin allowed the quenching assay of thrombin activity in the presence of active plasmin. FITC-fibrinogen could be copolymerized with recalcified platelet poor plasma (isolated from citrated whole blood) to yield fibrin that was fluorogenic. Dequenching was observed when plasmin was used to degrade the fibrin formed from the platelet poor plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Structure-activity studies of the C-terminal segment of structurally reduced analogues of ET-1.

Structurally reduced analogues of endothelin-1 (ET-1) were synthesized by linking via aminocaproic acid (Aca) the segment 3-11 of ET-1 to C-terminal fragments of various lengths [16-21, 17-21,...,21]. Analogues were studied in their linear or cyclic form in the absence or presence of a formyl group on the Trp21 side-chain, and their biologic activities were tested using guinea pig lung parenchymal strips. The absence of the first disulfide bridge and the presence of the Aca spacer caused a slight decrease in activity. The presence of His16 is essential for the contractile activity of the monocyclic peptides. Formylation of these monocyclic analogues did not modify this behavior. Similarly, linear analogues carrying S-acetamidomethyl (Acm) functions and an Aca linker were still active. However, most formylated linear derivatives were partial agonists, whereas the addition of His16 caused a decrease in contractile activity. In these latter analogues, molecular modeling studies suggested that formylation produces different conformations.

Animals↗
PubMed1977

Vasodilation due to urokinase in the canine femoral circulation.

Based upon clinical observations, we hypothesize that the plasminogen activator urokinase is vasoactive in addition to being fibrinolytic and thrombolytic. The effects of intra-arterial injections and infusions of urokinase were investigated in the canine femoral circulation. Injections of human urine urokinase increased femoral artery blood flow in a dose-related fashion that was not significantly attenuated by beta adrenergic blockade, antihistamine treatment, heating, atropine treatment or kallikrein inactivation. The Ploug preparation of urine urokinase was somewhat more effective than the Abbott or Sterling-Winthrop preparations in causing this dilation. Some nonspecific inhibition of the vasodilator responses was produced by inhibition of plasminogen activation with epsilon-aminocaproic acid. The continuous infusion of urokinase increased femoral arterial flow but there was some tendency to escape. Further experiments seem indicated to determine potential application of local urokinase in clinical conditions where vasodilation and fibrinolysis-thrombolysis might be of value.

Animals↗
PubMed1996

Biological and molecular analyses of structurally reduced analogues of endothelin-1.

Structurally reduced analogues of endothelin-1 (ET-1) were synthesized through linking with an aliphatic spacer [aminocaproic acid (Aca)], segment 3-11 of ET-1 to carboxyl-terminal fragments of various lengths (16-21, 17-21,...,21). The peptides were prepared in their linear or cyclic form, and a formyl group was or was not introduced on the Trp21 side chain. Pharmacological studies were carried out with the guinea pig lung parenchyma paradigm and the rat thoracic aorta bioassay. In the rat aorta, an ET(A) receptor preparation, all of the analogues were inactive. However, in the lung parenchyma, we observed that among the linear formylated derivatives, [Cys(Acm)3,11,Trp(For)21]-(3-11)-Aca-(17-21)ET was a partial agonist. In this series, the presence of His16, as in [Cys(Acm)3,11,Trp(For)21]-(3-11)-Aca-(16-21)ET, caused a decrease in contractile activity, suggesting that the imidazole group disfavors the proper interaction of the linear molecule with the ETB receptors of the lung parenchyma. The loss of biological activity of the deformylated linear analogues strongly suggested that the formyl group played a stabilizing role in the structure of the linear molecules. Interestingly, molecular modeling studies indicated the adoption of different conformations by the formylated and the nonformylated analogues. In contrast, the stabilizing effect of the formyl group was not observed with the cyclic compounds. Furthermore, the presence of His16 favored the contractile activity of the cyclic peptides. Finally, the results demonstrated that the carboxyl-terminal residues 18-21 are required for the activity in the guinea pig lung parenchyma ETB receptors.

Animals↗
PubMed1996

A paradox of thrombogenesis by streptokinase and its prevention by iloprost and camonagrel.

Here we report that streptokinase is responsible for forming thrombi both in vitro on blood-superfused endothelial cells of rabbit aorta and in vivo on blood-superfused collagen strips in extracorporal circulation of anesthetized cats. This short-lasting paradoxical thrombogenic phase is followed by the expected long-lasting thrombolysis. The biphasic action of streptokinase occurred in vitro at concentrations of 100-2000 U/ml and in vivo at doses of 1000-3000 U/kg i.v. Both phases are mediated by endogenous plasmin as evidenced by deleting the streptokinase-induced thrombogenesis and thrombolysis following pretreatment with epsilon-aminocaproic acid or aprotinin. On the other hand, selective block of the paradoxical thrombogenesis was achieved after pretreatment with camonagrel, a thromboxane synthase inhibitor which raises plasma levels of endogenous prostacyclin, or with iloprost, a stable analog of prostacyclin. It is suggested that endogenous or exogenous prostacyclin inhibits activation of platelets by plasmin, and hence the thrombogenesis by streptokinase is abolished, while the beneficial thrombolytic action of streptokinase is augmented.

Animals↗
PubMed1996

Pharmacologic therapy of arteriovenous malformations.

Pharmacologic treatment of bleeding gastrointestinal arteriovenous malformations is difficult. These lesions should be treated pharmacologically only when endoscopic treatment is not successful and bleeding persists or when the lesions cannot be treated endoscopically due to their localization, mainly in the small bowel. These are only a limited number of studies available on the medical treatment of bleeding arteriovenous malformations. There is considerable evidence, however, that a combination of estrogens and progestagens significantly reduces the bleeding frequency and intensity and also the transfusion requirements in patients with high transfusion need. A few other drugs have been tried in patients with bleeding gastrointestinal arteriovenous malformations: danazol, octreotide, desmopressin, and aminocaproic acid. The experience with these drugs, however, is limited to case reports or to small series of patients.

Arteriovenous Malformations↗
PubMed1977

Disseminated intravascular coagulation.

The diagnosis of disseminated intravascular coagulation associated with intracranial pathology is discussed. This pathological entity is characterized by a diffuse bleeding diathesis. Laboratory studies suggest a consumption of all clotting and fibrinolytic factors with an elevation of fibrin split products as a sign of the fibrinolytic activity. The treatment consists of the administration of packed platelets and fresh frozen plasma to replace the consumed coagulation factors. Heparinization is recommended early to prevent further consumption of coagulation factors and epsilon-aminocaproic acid is recommended later after acute fibrinolysis is diagnosed. Constant coaguloanalytic monitoring is necessary. Although the etiology with massive injury to brain tissue is possibly secondary to autotransfusion of brain tissue thromboplastin, other causes such as hypotension, anoxia, acidosis and hemolysis must be considered.

Blood Coagulation Tests↗
PubMed1997

Enhancement of plasminogen binding to U937 cells and fibrin by complestatin.

Plasminogen binds to endothelial and blood cells as well as to fibrin, where the zymogen is efficiently activated and protected from inhibition by alpha 2-antiplasmin. In the present study we have found that complestatin, a peptide-like metabolite of a streptomyces, enhances binding of plasminogen to cells and fibrin. Complestatin, at concentrations ranging from 1 to 5 microM, doubled 125I-plasminogen binding to U937 cells both in the absence and presence of lipoprotein(a), a putative physiological competitor of plasminogen. The binding of 125I-plasminogen in the presence of complestatin was abolished by epsilon-aminocaproic acid, suggesting that the lysine binding site(s) of the plasminogen molecule are involved in the binding. Equilibrium binding analyses indicated that complestatin increased the maximum binding of 125I-plasminogen to U937 cells without affecting the binding affinity. Complestatin was also effective in increasing 125I-plasminogen binding to fibrin, causing 2-fold elevation of the binding at approximately 1 microM. Along with the potentiation of plasminogen binding, complestatin enhanced plasmin formation, and thereby increased fibrinolysis. These results would provide a biochemical basis for a pharmacological stimulation of endogenous fibrinolysis through a promotion of plasminogen binding to cells and fibrin.

Cell Line↗
PubMedDate not supplied

[Exchanges of proteins, especially fibrinogen, between blood and lymph].

Microvessels of rat mesentery were used for the study. Proteins marked with fluorescent dyes are first visible in the vascular terminations. After 10 minutes they pass into the perivascular tissues where very fine reticular structures appear. The passage begins at the level of the venules, and continues in the interstitial tissue in the form of fibrils; the extravasation does not have a diffuse character (this has also been verified by other techniques). The ultraviolet microscope permits localization of the proteins because of their specific absorption. These experiments were conducted with labelled fibrinogen. Fibrinogen showed a high degree of selective affinity for the vessel wall, especially for that of the venules, and much less or none at all for that of the arterioles or the capillary loops. Fibrinogen is also found in the interstitial spaces and in the lymphatic vessels. The deposits in the vessel walls occur with a normal speed of blood flow. These intravenous deposit may be prevented by means of a preliminary injection of heparin. On the other hand they are very marked after inhibition of fibrinolysis by epsilon-aminocaproic acid and also by the addition of small doses of thrombin.

Animals↗
PubMed1997

Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene.

Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue- and urokinase-type plasminogen activators, is considered a critical regulator of the fibrinolytic system. We previously reported a child with abnormal bleeding and complete PAI-1 deficiency caused by a frame-shift mutation in exon 4 of the PAI-1 gene. The purpose of this study was to provide genetic and clinical data on the extended pedigree of the original proband to better define the phenotype associated with PAI-1 deficiency. Allele-specific oligonucleotide hybridization was used to genotype individuals, and serum PAI-1 antigen was measured by enzyme-linked immunosorbent assay. By this approach we have identified 19 individuals who are heterozygous for the PAI-1 null allele and 7 homozygous individuals with complete PAI-1 deficiency. Clinical manifestations of PAI-1 deficiency were restricted to abnormal bleeding, which was observed only after trauma or surgery in homozygous affected individuals. A spectrum of bleeding patterns was observed, including intracranial and joint bleeding after mild trauma, delayed surgical bleeding, severe menstrual bleeding, and frequent bruising. Fibrinolysis inhibitors, including epsilon-aminocaproic acid and tranexamic acid, were effective in treating and preventing bleeding episodes. Other than abnormal bleeding, no significant developmental or other abnormalities were observed in homozygous PAI-1-deficient individuals. Heterozygous PAI-1 deficiency was not associated with abnormal bleeding, even after trauma or surgery. These observations define the clinical spectrum of PAI-1 deficiency and provide additional evidence to support the hypothesis that the primary function of plasminogen activator inhibitor-1 in vivo is to regulate vascular fibrinolysis.

Adolescent↗
PubMedDate not supplied

Individual strategies of hemostasis for thoracic aortic surgery.

The problem of altered hemostasis remains a major challenge during thoracic aortic surgery. Bleeding is associated with a marked increase in morbidity and mortality. The hemostatic derangements are caused by multiple interrelated factors including interference with the vascular integrity, extensive surgical dissection, transient need for complete inhibition of the normal coagulation process, large blood products and fluid requirements, hemodilution, hypothermia, extensive ischemia and reperfusion, activation of systemic inflammatory responses, interference with fibrinolysis, and the use of extracorporeal circulation systems. Acquired coagulopathy must be specifically diagnosed and treated. Platelet deficiencies, both qualitative and quantitative, are the most predictable and consistent disturbance in the hemostatic function and the most common cause of intraoperative and postoperative bleeding. Precise surgical technique is essential to prevent blood loss. Topical agents should not be used for and cannot correct imperfections in surgical technique. Nonspecific measurements that are useful to decrease intraoperative blood loss include strict control of blood pressure and hemodynamic status, the induction of mild controlled hypotension, and the reversal of hypothermia. Rewarming may produce clear procoagulant effects by improving the efficacy of platelets and clotting factors. Platelet dysfunction can be reduced by several pharmacological interventions including acid aminocaproic, desmopressin and aprotinin; however, efficacy and safety are still being established. The most important factorS regarding safety in thoracic aortic surgery are a secure suture line and the experience of the surgical and anesthesiology teams.

Aortic Dissection↗
PubMed1976

Evidence that functional subunits of antihemophilic factor (Factor VIII) are linked by noncovalent bonds.

Partially purified human antihemophilic factor (AHF, factor VIII), when treated with high concentrations of salt, has been shown to dissociate into two components: one, of relatively low molecular weight, possesses procoagulant activity, and the other, of higher molecular weight, forms precipitates with heterologous antiserum against AHF and supports ristocetin-induced platelet aggregation. The ease of separation suggests that the two components in the native state might be held together by noncovalent bonds. Earlier observations do not exclude the possibility that the subunits may be covalently bonded in nature but might be severed by plasma proteolytic enzymes during laboratory manipulation. The issue was examined by preparing partially purified AHF from fresh human plasma in the presence of protease inhibitors, including benzamidine, soybean trypsin inhibitor, epsilon-aminocaproic acid, heparin, and hirudin. Under these conditons, gel filtration in the presence of 0.25 M calcium chloride and 0.001 M benzamidine resulted in its separation into two components, having properties identical to those separated in the absence of these protease inhibitors. The inhibitor mixture blocked generation and action of streptokinase- and kaolin-activated plasmin from plasma, and protected both plasma AHF and partially purified AHF from the action of thrombin. Surface-induced activation of PTA (factor XI) was partially inhibited, and that of Christmas factor (factor IX) was completely inhibited. This observation provides further evidence that in the native state the high- and low-molecular-weight components of preparations of antihemophilic factor are held together by noncovalent bonds.

Benzamidines↗
PubMed1997

Effects of fibrin adhesive material (Tissucol) on alveolar healing in rats under stress.

The effects of Tissucol on alveolar healing following stress were evaluated histologically, comparing three groups of 28 male albino rats each. Stress was applied and their right upper incisors were extracted. Group A served as an empty control site. In Group B, Tissucol was applied into the alveolar cavity. Group C received local antifibrinolytic treatment (alveolar irrigation with epsilon-aminocaproic acid solution) before implant of Tissucol into the tooth socket. Four animals in each group were killed at 1, 3, 6, 9, 15, 21 and 24 days after surgery. Results showed that: 1) Tissucol did not interfere with connective and osseous tissue formation; 2) Tissucol allowed new bone formation; 3) Tissucol residues in Group B in sections of 24-day specimens did not impair healing; 4) Tissucol was usually completely resorbed and healing was complete 24 days after surgery in Group C.

Alveolar Process↗
PubMedDate not supplied

[Treatment of neuroautonomic rhinopathy].

With the aim of treating vasodilatory forms of neurovegetative rhinopathy the authors applied injections of a mixture into the body of the mucous membrane covering the anterior ends of the inferior nasal concha, the mixture consisting of 1 ml of 6% novocaine solution, 1 ml of 6% thiamine bromide solution and 0.5 ml (12.5 mg) of hydrocortisone emulsion. The course of treatment included 10 injections administered with 3 day intevals. 0.5 aminocaproic acid was taken orally 3 times a day during one month. Drops were used locally: 500 000 units of polymixine, 0,5% dimedrole-20.0, hydrocortisone emulsion-5.0; 8 drops of this mixture were introduced into the nose twice a day during 2 weeks. An ointment was used for the night consisting of sodium albucide-2.0, menthol-0.1, camphor-0.1, anesthesine-0.4, oil of eucalyptus-1.0, camphor-0.1, anesthesine-0.4, oil of eucalyptus-1.0, vaseline and lanolin-10.0 each.

Adolescent↗
PubMed1998

Rapid preparation of small-volume autologous fibrinogen concentrate and its same day use in bleb leaks after glaucoma filtration surgery.

The authors evaluated small-volume preparation of autologous fibrin glue (AFG) and same day use in postglaucoma filtration surgery patients with Seidel positive bleb leaks and determined fibrinogen concentrations in autologous fibrinogen concentrates (AFCs) from 10 volunteers. Thirty milliliters of blood was centrifuged (5 min, 2400 x g); plasma was frozen (5 min-ethanol and ice), thawed (1-6 C, 30-60 min), and centrifuged (10 min, 5 C, 2800 x g); and the precipitate was transferred to a 1.0-ml tuberculosis syringe. Thrombin (1000 U) was dissolved (0.8 sterile water, 0.2 ml aminocaproic acid) and warmed (37 C). Average preparation time was 90 minutes. Alternating drops of AFC and thrombin were applied to bleb leaks until AFC clotted. Seidel testing with fluorescein determined success. AFC was prepared from 10 volunteers and fibrinogen was measured. AFG was initially successful with two (Seidel negative) eyes; one eye remained negative. AFG was unsuccessful in one briskly Seidel-positive leak. Mean +/- SD fibrinogen concentration in AFCs from the 10 volunteers was 2314 +/- 643 mg/dl (range 1608-3431 mg/dl). AFG may successfully close bleb leaks in outpatient settings. Brisk aqueous flow may impair effectiveness of AFG. Fibrinogen concentrations were comparable with previous reports.

Administration, Topical↗