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 1,135 records · Page 63Linked to original sources
PubMed1986

Antifibrinolytic therapy of experimentally grown malignant brain tumors.

This study was designed to evaluate the effect of an inhibitor of plasminogen activation on the growth of a human glioblastoma line grown in nude mice up to the seventh passage. The tumors produced plasminogen activators and showed histological characteristics similar to those of the original tumor. Three groups of mice were studied. Group A received 5% epsilon aminocaproic acid (EACA); Group B received 2.5% EACA; and Group C served as a control. There was no statistical difference among the three groups with regard to: 1) age at time of tumor transplantation; 2) the interval between implant and treatment; or 3) tumor volume at time of treatment. Blood measurements of EACA, performed in a limited number of animals, have shown that the drug at 5% concentration had reached toxic levels. Statistically significant differences between the three groups were noted in the following categories: 1) rate of tumor growth; 2) tumor volume at time of death, where Group A had smaller tumors than Group C; and 3) mean survival times of Groups A and B as compared to Group C. A statistically significant negative correlation was found between the rate of tumor growth and the length of survival of animals in Group C, while no correlation could be found for either Group A or B, indicating that the antifibrinolytic therapy modified this important biological variable. This study supports the hypothesis that the fibrinolytic system plays a role in the growth and development of malignant gliomas and that interference with the fibrinolytic system may retard the growth of these tumors grown in nude mice.

Aminocaproates↗
PubMed1985

[Effectiveness of the combined use of an inactivated vaccine and a proteolysis inhibitor in the prevention of experimental influenza].

The prophylactic effects produced by different types of antiviral preparations, used separately or in combination, in experimental lethal infection induced by influenza virus AO/32 (H0N1) in mice are compared. The use of inactivated vaccine and E-aminocaproic acid (E-ACA), a proteolysis-inhibiting agent, was studied. The qualitative characterization and quantitative evaluation of the anti-influenza effect were carried out by the method of multifactor analysis with the use of a computer after the optimum second-order plan based on the mathematical theory of experiment. This made it possible to determine the best combination of the preparations and their doses, to establish the time of the formation of reliable protection from influenza in mice. The prophylactic effect produced by the use of E-ACA alone and the capacity of this preparation for enhancing the protective action of inactivated influenza vaccine were established. Mathematical analysis revealed the optimum value of the four factors under study: the dose of the vaccine, the dose of E-ACA, the lapse of time between the injection of the preparations and the challenge of the animals, as well as the infective dose of the pathogenic virus. A special experiment made in the study of these data confirmed that the specific formation of a high level of anti-influenza protection in mice can be achieved by the combined use of the vaccine and the inhibitor of proteolysis.

Aminocaproic Acid↗
PubMedDate not supplied

Prevention of damage in acute spinal cord injury by peptides and pharmacologic agents.

Cats were used as models of traumatic spinal cord injury. Each experimental animal received a 500 g-cm force to the exposed dura at the level of thoracic fourth vertebra. Somatosensory evoked potentials (SEPs), carotid arterial blood pressure (BP), and abdominal aorta blood flow in the treated groups were compared with those of the control group. The three treated groups received naloxone (5 mg/kg), TRH (5 mg/kg), and a combination of methyl-prednisolone sodium succinate (MP, 35 mg/kg) and epsilon-aminocaproic acid (EACA, 350 mg/kg). The SEPs which were done only in the naloxone treated group approached "normalcy" 24-26 hours after trauma as compared with the absence of SEPs in traumatized untreated group. In all three groups, the treatment increased the blood flow in abdominal aorta significantly. Morphine sulfate increased substance P (SP) immunoreactivity in the dorsal and ventral gray matter. Naloxone not only reversed this effect, it depleted SP below the saline control level. In order to establish that lipid free radicals are responsible for damage to biological membranes, their effects were also investigated in vitro: 14C-GABA uptake by mouse cortical slices which had decreased by 33% in the presence of superoxide (. O-2) generating system, horseradish peroxidase (HRP), was reduced only by 9% when superoxide dismutase was added to the medium. The latter also protected the nerve endings from damage by (. O-2) as examined by electron microscopy. It is concluded that the agents used in this study produce their ameliorating effects by virtue of their anti-inflammatory, anti-oxidant, and membrane stabilizing properties in addition to their effect on enhancing the regional microcirculation. The release of SP by naloxone may be responsible for the increase in blood flow. The consequences of traumatic injury as depicted in Fig. 1 are discussed at length.

Aminocaproates↗
PubMed1994

Natural and synthetic antifibrinolytics in adult cardiac surgery: efficacy, effectiveness and efficiency.

Epsilon-aminocaproic acid and tranexamic acid, two synthetic antifibrinolytics, and aprotinin, an antifibrinolytic derived from bovine lung, are used to reduce excessive bleeding and transfusion of homologous blood products (HBP) after cardiac surgery. This review analyzes the studies on the utilization of antifibrinolytics in adult cardiac surgery according to the epidemiological concepts of efficacy, effectiveness and efficiency. A majority of published studies confirm the efficacy of antifibrinolytics administered prophylactically to reduce postoperative bleeding and transfusion of HBP. More studies are needed, however, to compare antifibrinolytics and determine if any one is superior to the others. Despite their demonstrated efficacy, antifibrinolytics are only one of the options available to diminish the use of HBP. Other blood-saving techniques, surgical expertise, temperature during cardiopulmonary bypass and respect of established transfusion guidelines may modify the effectiveness of antifibrinolytics to the point where antifibrinolytics may not be necessary. At this time, insufficient data have been published to perform a cost vs benefit analysis of the use of antifibrinolytics. This complex analysis takes into account not only direct costs (cost of the drug and of blood products), but also the ensuing effects of treatment such as: length of stay in the operating room, in the intensive care unit and in the hospital; need for surgical re-exploration; treatment of transfusion or drug-related complications, etc. In particular, the risk of thrombotic complications associated with antifibrinolytics is the subject of an ongoing, unresolved controversy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Reducing the risk of rebleeding before early aneurysm surgery: a possible role for antifibrinolytic therapy.

Previous studies on the initial nonoperative management of aneurysmal subarachnoid hemorrhage (SAH) demonstrated that antifibrinolytic therapy reduced the risk of rebleeding by approximately 50%; however, prolonged antifibrinolytic treatment was associated with an increase in the incidence of hydrocephalus and delayed ischemic deficit. When early surgical intervention became routine for ruptured aneurysms, the use of antifibrinolytic therapy diminished. However, early surgery is generally performed in the first several days after SAH and the risk of rebleeding remains until the aneurysm is obliterated. Based on a review of the literature, the authors formed two hypotheses: 1) the high-dose intravenous administration of epsilon-aminocaproic acid (EACA), an antifibrinolytic agent, might reduce the risk of recurrent hemorrhage in the interval between SAH and early surgical intervention, and 2) a short course of EACA might not produce the increase in complications previously associated with its prolonged administration. The use of preoperative high-dose EACA therapy was evaluated in 307 patients to determine its safety and efficacy in reducing the incidence of rebleeding before early aneurysm surgery. All patients were admitted within 3 days of their SAH and were classified as Hunt and Hess Grades I to III. Only four patients (1.3%) suffered a recurrent hemorrhage. This compares favorably to the rebleeding rate of 5.7% reported for the early surgery group in the International Cooperative Study on the Timing of Aneurysm Surgery. The incidence of hydrocephalus or symptomatic vasospasm was not unduly elevated in patients receiving preoperative EACA. Thirty-five patients (11.4%) needed temporary cerebrospinal fluid drainage during their hospitalization and, overall, 8.8% required a ventriculoperitoneal shunt. The mean age of the patients who required a shunt was nearly 10 years older than the general study population. Seventy-one patients (23%) developed symptomatic vasospasm and 8.1% suffered a stroke. This study indicates that a brief course of high-dose EACA is safe and may be beneficial in diminishing the risk of rebleeding in good-grade patients prior to early surgical intervention. Further investigation is planned based on these promising results.

Adult↗
PubMed1988

Follicular development is impaired by inhibitors of serine proteases in the rat.

Serine proteases such as plasminogen activators are produced by granulosa cells both in vivo and in vitro and have been implicated in the process of ovulation. For a study of potential roles of serine proteases in early follicular development, immature rats were injected with pregnant mare serum gonadotropin, followed 2 hours later by laparotomy and injection of the serine protease inhibitors benzamidine and epsilon-aminocaproic acid into the bursa of one ovary. As a control, saline solution was injected into the contralateral bursa. Animals were put to death 48 hours after injection of serine protease inhibitors, and three to five randomly selected longitudinal sections were evaluated by computerized morphometry. The area occupied by antral follicles relative to the total cross-sectional area of each section was computed. Resultant ratios from serine protease inhibitor-treated ovaries were compared with those from contralateral control ovaries. Ninety-three percent of serine protease inhibitor-treated ovaries showed a reduction in antral follicular size when compared with corresponding control ovaries, which is indicative of inhibitory effects of serine protease inhibitor treatment on folliculogenesis. To further investigate this effect, ovulation was induced by human chorionic gonadotropin administration 48 hours after pregnant mare serum gonadotropin and 46 hours after serine protease inhibitor or saline solution treatment. Animals were put to death 20 hours later and the number of oocytes ovulated into oviducts was determined. Oviducts from serine protease inhibitor-treated ovaries contained 51% fewer oocytes than their control counterparts. Artifacts of surgical stress or vascular diffusion of serine protease inhibitor from treated to control sides were ruled out by appropriate control experiments. We conclude that early serine protease inhibitor treatment of pregnant mare serum gonadotropin-stimulated rat ovaries impairs folliculogenesis. Thus, in addition to involvement in ovulation, serine proteases appear to play important roles throughout follicular development.

Aminocaproic Acid↗
PubMed1988

Control of human plasminogen activation.

The activation of Glu1-plasminogen (Glu-Pg) by streptokinase (SK), urokinase (UK) and tissue plasminogen activator (tPA) is under rigorous control by molecules such as epsilon-aminocaproic acid (EACA), fibrinogen (Fg), fibrin (Fn) and, as we have recently discovered, anions. This presentation will focus on the biochemical mechanisms that are involved in these processes. In the case of activation by SK, a species of activator complex, composed of Glu-Pg and SK, can be identified that is inhibited by anions, such as Cl-, and stimulated by Fg and Fn. This species rapidly decays to another activator complex, also consisting of Glu-Pg and SK, that is much less sensitive to control by these effector molecules. The most stable activator complex, containing equimolar SK and plasmin, is not affected to a great extent by anions, Fg or Fn. In the overall activation of Glu-Pg by SK, Cl- behaves as a mixed inhibitor, with a Ki of 6.4-9.2 mM, and Fg functions as a mixed activator, displaying a Ka of 110-240 nM. These results show that activation of Glu-Pg by SK in physiological samples would be considerably inhibited by Cl- in the absence of Fg. The activation of Glu-Pg by both high- and low-molecular weight UK is also inhibited by Cl-, but is stimulated by EACA. The inhibition by Cl- does not occur in the presence of concentrations of EACA that saturate its weak binding sites on Glu-Pg, and the stimulation by EACA is maximally exhibited in the presence of Cl-.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminocaproic Acid↗
PubMed1994

Inhibitory effects of lysine analogues on t-PA induced whole blood clot lysis.

The lysine analogues epsilon-aminocaproic acid (EACA) and trans-4-amino-methyl cyclohexane carboxylic acid (AMCA) are used to prevent excessive bleeding in patients with coagulopathies, such as hemophilia and thrombocytopenia, or in those who have received tissue plasminogen activator (t-PA). However, their relative efficacy in inhibiting lysis of clots that have been formed in the presence of exogenous t-PA or that have been formed and then exposed to exogenous t-PA has not been well characterized. The present study utilized blood from normal volunteers and 125I-fibrinogen in a dilute whole blood clot assay to determine the relative concentrations of lysine analogues required for inhibition of clot lysis induced by exogenous t-PA. AMCA (0.06 mM) and EACA (0.6 mM) were effective in prolonging clot lysis if (1) whole blood clots were formed and then exposed to a lysine analogue and exogenous t-PA or if (2) whole blood clots were formed in the presence of exogenous t-PA and a lysine analogue. However, their inhibitory effect was markedly reduced if clots were formed in the presence of t-PA and then exposed to either of the lysine analogues. The analogues did not inhibit the initial binding of t-PA to fibrin. They did inhibit binding of plasminogen to fibrin as well as the activation of plasminogen by t-PA in the absence of fibrin. The data suggest that lysine analogues, even at low concentrations, reduce the rate of t-PA induced whole blood clot lysis by several mechanisms.

Aminocaproic Acid↗
PubMed1987

Endothelial linings: the effect of serine protease inhibition.

The purpose of this investigation was to determine if the inhibition of the serine proteases, thrombin and plasmin, by heparin and epsilon-aminocaproic acid (EACA) would improve endothelial cell retention on synthetic grafts. Endothelium was harvested from the external jugular veins of mongrel dogs using an enzymatic technique. The cells were grown in tissue culture for 3-4 weeks, labeled with 111In oxine, inoculated (2000 cells/mm2) into fibronectin-coated 4 mm-diameter tubes of polyester elastomer (PE, Hytrel 4056, DuPont), and cultured for 18 hr. Each animal received iv heparin (100 U/kg) prior to implantation, and a 4 X 30-mm segment of the culture-lined PE was interposed in the dog's own carotid artery. After 6 hr of flow the grafts were perfusion fixed; the percentage of endothelial retention was determined by 111In counting, and the surfaces of the grafts were analyzed by scanning electron microscopy. Six experiments were performed in each of three treatment groups. Animals in Group I received no additional drugs. Group II animals received a continuous infusion of heparin at 30 U/kg/hr. Group III animals received a bolus of 200 mg/kg of EACA with the initial heparin dose and a continuous infusion of heparin at 30 U/kg/hr and EACA at 200 mg/kg/hr. Group I grafts retained an average of 36.1 +/- 23.3% of the cells; Group II retained 67.5 +/- 24.9%; and Group III retained 83.4 +/- 9.8%. Although continuous heparin infusion resulted in a trend (P = 0.067) toward better retention, a combined infusion of heparin and EACA resulted in significantly better retention (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminocaproic Acid↗
PubMedDate not supplied

Immunological properties of allergen chemically modified with synthetic copolymer of N-vinylpyrrolidone and maleic anhydride.

Several conjugates of model allergen ovalbumin (OA) and the copolymer of N-vinyl pyrrolidone and maleic anhydride (VMA) modified with epsilon-aminocaproic acid (Acp) were prepared in different OA/Acp-VMA ratios. All conjugates were separated by ultrafiltration and analyzed by HPLC. Their compositions were determined by amino acid analysis and UV spectrometry. To detect immunogenicity, all conjugates were injected intraperitoneally into (CBAxC57BL/6)F1 mice three times in 3-week intervals in OA doses equivalent to 0.5, 10, and 100 micrograms/mouse. Only the conjugate containing 20%OA (OA(20%)-Acp-VMA) did not induce significant quantities of anti-OA IgE, but did induce anti-OA IgG antibodies in dose-dependent manner comparable to that of unmodified OA. Mixtures of OA and Acp-VMA or OA modified only with VMA without Acp activation with Acp induced dose-dependent anti-OA IgE and IgG antibody formation comparable to that of OA. Using passive cutaneous anaphylaxis, RAST inhibition and leukocyte histamine release, a significant reduction of allergenicity was noted using OA(20%)-Acp-VMA. This conjugate stimulated activation of the OA-specific T-cell hybrid 3DO-548 comparable to that of unconjugated OA. During experimental allergen-specific hyposensitization with OA(20%)-Acp-VMA, suppression of anti-OA IgE response and elevation of anti-OA IgG responses were noted when compared with unmodified OA. Selective blockade of B-cell epitopes of allergen may occur using the carrier Acp-VMA to reduce allergenicity while not affecting T-cell epitopes, thereby preserving immunogenicity. This approach of chemical modification of allergen suggests new opportunities in the creation of preparations for allergen-specific immunotherapy.

Allergens↗
PubMed2003

Impact of AMICAR on hemorrhagic complications of ECMO: a ten-year review.

PURPOSE: Preliminary studies have shown aminocaproic acid (AMICAR), an inhibitor of fibrinolysis, reduced the incidence of intracranial hemorrhage and significant surgical site bleeding in patients on extracorporeal membrane oxygenation (ECMO). The purpose of this analysis is to determine if these benefits remain when AMICAR is used in a large population. METHODS: ECMO patients from a single pediatric institution, with routine use of AMICAR for "high-risk" patients, were evaluated retrospectively from 1991 to 2001. Data including diagnosis, duration of support, significant complications, and survival were recorded. These variables were compared with those of the Extracorporeal Life Support Organization (ELSO), an international ECMO registry, using a chi2 test. P less than.05 was deemed significant. RESULTS: ECMO was used 431 times during the 10-year study period. A total of 298 patients received AMICAR, most frequently for surgical procedures. The survival rate was not statistically different in the study group when compared with the ELSO Registry (P =.06). The rate of neonatal intracranial hemorrhage was not significantly different between the 2 groups (P =.133); however, the rate of surgical site bleeding was significantly reduced in the study population (P =.005). Decrease in surgical site bleeding was particularly evident in cardiac patients (P <.001). CONCLUSIONS: In this large experience, use of AMICAR for high-risk patients on ECMO did not appear to alter the rate of neonatal intracranial hemorrhage, but did significantly reduce the incidence of surgical site bleeding. AMICAR remains a valuable tool for the prevention of hemorrhage in patients undergoing operation prior to or while on ECMO.

Adult↗
PubMed2001

Hyperfibrinolytic activity in hospitalized cirrhotic patients in a referral liver unit.

OBJECTIVE: Increased frequency of hyperfibrinolytic activity was reported in patients with cirrhosis. However, the incidence, clinical presentation, and the parameters related to hyperfibrinolysis remain largely unknown in these patients. By utilizing euglobulin lysis time (ELT) and other clinical coagulation tests, the present study investigated the incidence of and clinical parameters related to hyperfibrinolytic activity, and assessed predicting factors to epsilon-aminocaproic acid (EACA) treatment in cirrhotic patients with hyperfibrinolysis in a liver unit. METHODS: The study included 86 consecutive patients who were referred and admitted to a referral liver unit for various liver diseases. The mean age was 50.0 yr, with a male: female ratio of 60:26. Sixty-six patients (76.7%) were Hispanic and 75 (87.2%) were cirrhotic. The etiologies of liver diseases included alcoholic liver disease (n = 68, 79.1%), hepatitis B (n = 2, 2.3%), hepatitis C (n = 6, 7.0%), autoimmune hepatitis (n = 3, 3.5%), cryptogenic liver disease (n = 4, 4.7%), and hepatocellular carcinoma (n = 3, 3.5%). Coagulation studies included ELT, PT, PTT, fibrinogen, D-dimer, and fibrin degradation product levels. RESULTS: Hyperfibrinolytic activity as reflected by shortened ELT was present in 27/75 cirrhotic (31.3%) but 0/11 noncirrhotic patients, which was significantly correlated with higher Child-Pugh (C-P) class, abnormal levels of PT, PTT, fibrinogen, platelet count, and total bilirubin. Shortened ELT was more frequently seen in patients with hepatic decompensation and mucocutaneous bleeding, although these relationships were not statistically significant. In 27 patients with hyperfibrinolysis, five (18.5%) required EACA treatment for progressive mucocutaneous bleeding and/or hematoma. EACA treatment was significantly associated with higher C-P scores; greatly shortened ELT (< or =50% of normal value); and abnormal levels of fibrinogen, total bilirubin, and PT, indicating that these factors may serve as predictors for EACA treatment. CONCLUSION: Hyperfibrinolytic activity was seen in 31.3% of patients with cirrhosis, which is correlated with higher C-P scores; abnormal PT, PTT, fibrinogen level, and platelet count; and hyperbilirubinemia. Patients who received EACA treatment usually have a more severe hyperfibrinolytic activity as indicated by shortened ELT and low level of fibrinogen, and more severe liver disease as indicated by higher C-P scores and hyperbilirubinemia.

Aged↗
PubMed1999

Recombinant kringle IV-10 modules of human apolipoprotein(a): structure, ligand binding modes, and biological relevance.

The kringle modules of apolipoprotein(a) [apo(a)] of lipoprotein(a) [Lp(a)] are highly homologous with kringle 4 of plasminogen (75-94%) and like the latter are autonomous structural and functional units. Apo(a) contains 14-37 kringle 4 (KIV) repeats distributed into 10 classes (1-10). Lp(a) binds lysine-Sepharose via a lysine binding site (LBS) located in KIV-10 (88% homology with plasminogen K4). However, the W72R substitution that occurs in rhesus monkeys and occasionally in humans leads to impaired lysine binding capacity of KIV-10 and Lp(a). The foregoing has been investigated by determining the structures of KIV-10/M66 (M66 variant) in its unliganded and ligand [epsilon-aminocaproic acid (EACA)] bound modes and the structure of recombinant KIV-10/M66R72 (the W72R mutant). In addition, the EACA liganded structure of a sequence polymorph (M66T in about 42-50% of the human population) was reexamined (KIV-10/T66/EACA). The KIV-10/M66, KIV-10/M66/EACA, and KIV-10/T66/EACA molecular structures are highly isostructural, indicating that the LBS of the kringles is preformed anticipating ligand binding. A displacement of three water molecules from the EACA binding groove and a movement of R35 bringing the guanidinium group close to the carboxylate of EACA to assist R71 in stabilizing the anionic group of the ligand are the only changes accompanying ligand binding. Both EACA structures were in the embedded binding mode utilizing all three binding centers (anionic, hydrophobic, cationic) like plasminogen kringles 1 and 4. The KIV-10/T66/EACA structure determined in this work differs from one previously reported [Mikol, V., Lo Grasso, P. V. and, Boettcher, B. R. (1996) J. Mol. Biol. 256, 751-761], which crystallized in a different crystal system and displayed an unbound binding mode, where only the amino group of EACA interacted with the anionic center of the LBS. The remainder of the ligand extended into solvent perpendicular to the kringle surface, leaving the hydrophobic pocket and the cationic center of the LBS unoccupied. The structure of recombinant KIV-10/M66R72 shows that R72 extends along the ligand binding groove parallel to the expected position of EACA toward the anionic center (D55/D57) and makes a salt bridge with D57. Thus, the R72 side chain mimics ligand binding, and loss of binding ability is the result of steric blockage of the LBS by R72 physically occupying part of the site. The rhesus monkey lysine binding impairment is compared with that of chimpanzee where KIV-10 has been shown to have a D57N mutation instead.

Aminocaproic Acid↗
PubMed1997

The solution phase interaction between apolipoprotein(a) and plasminogen inhibits the binding of plasminogen to a plasmin-modified fibrinogen surface.

In the present study, we assessed the binding of recombinant forms of apolipoprotein(a) [r-apo(a)] to plasminogen. Apo(a)-plasminogen interactions were demonstrated to be lysine-dependent, as they were abolished by the addition of epsilon-aminocaproic acid. Binding of r-apo(a) and plasma-derived Lp(a) to Glu-plasminogen was assessed in solution using a mutant form of recombinant plasminogen [Plg(S741C)] labeled at the active site with 5'-(iodoacetamido)fluorescein. High-affinity binding of apo(a) to plasminogen was observed with the 17-kringle r-apo(a) (Kd = 20.1 +/- 3.3 nM) as well as with plasma-derived Lp(a) (Kd = 5.58 +/- 0.08 nM). Binding studies using various truncated and mutant forms of r-apo(a) demonstrated that sequences within apo(a) kringle IV types 2-9 and the strong lysine binding site (LBS) in apo(a) kringle IV type 10 are not required for high-affinity binding to plasminogen. In all cases, the binding stoichiometry for the apo(a)-plasminogen interaction was determined to be 1:1. Binding data obtained using a 17-kringle r-apo(a) derivative lacking the protease-like domain (17KDeltaP; Kd = 3158 +/- 138 nM) indicate that sequences within the protease-like domain of apo(a) mediate its interaction with LBS in plasminogen. We determined that r-apo(a) and plasminogen bind to distinct sites on plasmin-modified fibrinogen with the concentration of plasminogen binding sites exceeding the concentration of r-apo(a) sites by a factor of 10. Furthermore, r-apo(a) is capable of inhibiting the binding of plasminogen to plasmin-modified fibrinogen surfaces, an effect which we show is attributable to the formation of a solution phase apo(a)/plasminogen complex which exhibits a greatly reduced affinity for plasminogen binding sites on plasmin-modified fibrinogen. The results of this study provide new insights into the mechanism by which apo(a) and Lp(a) may inhibit fibrinolysis, thus contributing to the atherothrombotic risk associated with this lipoprotein.

Aminocaproic Acid↗
PubMed2000

Mechanism of antinephritic effect of proteinase inhibitors in experimental anti-GBM glomerulopathy.

We have previously documented amelioration of rat autologous anti-GBM nephritis with the antiproteolytic drugs epsilon-aminocaproic acid (EACA) and aprotinin, given from the day of induction or later in the course of disease. In the present study we investigated potential mechanisms of this effect by assessing interactions of the drugs with proteinase-dependent generation of superoxide anion in glomeruli, and their influence on both GBM degradation in vitro and activity of glomerular proteolytic enzymes. Release of O2- by enzymatically disrupted glomeruli, isolated from nephritic control or EACA/aprotinin-treated rats, was measured with the ferricytochrome reduction method and its activity was correlated with proteinuria and glomerular cellularity at the early phase of the disease. The hydroxyproline release assay was used to quantitate degradation of rat GBM in vitro by leukocyte proteinases stimulated by phorbol myristate acetate (PMA), in the presence or absence of EACA and aprotinin. Finally, the activities of elastase, cathepsins B and L, and plasmin, together with collagenase-like activity, were assessed fluorimetrically in homogenates of glomeruli isolated from control and antiproteolytic-drug-treated nephritic rats. EACA and aprotinin notably inhibited production of superoxide by nephritic glomeruli (by 47% and 66%, respectively), and this effect was not significantly correlated with proteinuria or glomerular hypercellularity at the early stage of disease. On the other hand, generation of O2- by glomeruli of untreated nephritic rats was notably correlated with total glomerular cell counts and numbers of macrophages infiltrating glomeruli. PMA-stimulated neutrophils and macrophages caused degradation of isolated rat GBM in vitro, markedly attenuated in the presence of EACA (P<0.0005) and, to a lesser extent, by addition of aprotinin (P<0.01). The activity of elastase was significantly reduced in glomeruli of nephritic rats treated with EACA or aprotinin (both P<0.001), while activities of remaining proteinases were not appreciably affected. The beneficial influence of proteinase inhibitors on rat anti-GBM disease may be due, at least in part, to abrogation of superoxide generation in nephritic glomeruli. EACA and aprotinin also have potential to interfere with digestion of GBM, and both these effects may be related to suppression of glomerular elastase.

Aminocaproic Acid↗
PubMed2004

The effect of amicar on perioperative blood loss in idiopathic scoliosis: the results of a prospective, randomized double-blind study.

STUDY DESIGN: A prospective, randomized, double-blind Institutional Review Board-approved study evaluating the efficacy of Amicar (epsilon aminocaproic acid), an antifibrinolytic agent, in decreasing perioperative blood loss in idiopathic scoliosis. OBJECTIVES: To compare the perioperative (intraoperative and postoperative) blood loss and the need for autologous and homologous blood replacement in two groups of essentially identical patients undergoing a posterior spinal fusion for idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Reducing perioperative blood loss and the need for transfusion in patients undergoing spinal surgery is important to orthopedic surgeons. Recently, there has been interest in pharmacologic agents, particularly Amicar and Aprotinin, to assist in decreasing perioperative blood loss. In 2001, in a preliminary study, we demonstrated that Amicar appeared to be effective in reducing perioperative blood loss in patients with idiopathic scoliosis undergoing a posterior spinal fusion and segmental spinal instrumentation. This was a study of 28 consecutive patients receiving Amicar compared to a historical control group of the 31 previous consecutive patients with the same study criteria. The current study was performed to confirm our preliminary findings. METHODS: We analyzed the perioperative blood loss of 36 patients with idiopathic scoliosis who were blindly randomized by the operating room pharmacy into an Amicar and control group. The criteria to be included in the study was the same as the preliminary study: diagnosis of idiopathic scoliosis, age at surgery 11 to 18 years, posterior spinal fusion and segmental spinal instrumentation only, autogenous iliac crest bone graft or homologous cancellous bone graft, and a signed agreement to participate in the study. The patients in both groups had the same anesthetic technique, intraoperative procedure, instrumentation, postoperative management, and standardized indications for transfusions. RESULTS: Before surgery, the patients in both groups were essentially identical. The distribution of patients and their results was not known until the completion of the study. Patients in the Amicar group demonstrated a statistically significant decrease in perioperative blood loss and the need for autologous blood transfusion. Interestingly, this decrease was predominantly in the postoperative suction drainage. This may be due to elevated fibrinogen levels induced by Amicar. The patients taking Amicar had no intraoperative or postoperative thromboembolic complications. CONCLUSIONS: The results of this study confirmed that the use of intraoperative Amicar is a safe, effective, and inexpensive method to significantly reduce perioperative blood loss in patients with idiopathic scoliosis undergoing posterior spinal fusion and segmental spinal instrumentation. The results have allowed us to reduce our recommendation for perioperative autologous blood donation, thereby further decreasing costs.

Adolescent↗
PubMed1979

Immunoglobulin elution from multiple sclerosis brain.

Immunoglobulin (Ig) was eluted from multiple sclerosis (MS) brain tissue. Razor thin slices of white matter from 10 g of MS and control brains were washed with 5 liters of phosphate-buffered saline (PBS), then treated for 90 sec with acetic acid, pH 2.5, containing Pepstatin and epsilon-aminocaproic acid. The protein concentrations of the PBS washes and neutralized acid eluates were determined, and the eluates were assayed for Ig by competitive microradioimmunoassay using rabbit anti-human F(ab1)2. Successive PBS washes reduced extracellular protein to a very low level. Equivalent quantities of protein were recovered from 7 MS and 6 non-MS brain samples after PBS washing and acetic acid elution. However, the amount of protein needed for 50% inhibition of [125I]IgG binding to anti-human F(ab1)2 was significantly less in MS brain than in non-MS brain (P less 0.05). The Ig in brain eluates was present in the void volume of a DEAE cellulose column. The techniques described above facilitate the isolation and characterization of cell-surface Ig in MS brain.

Brain↗