scholarly journals DLBS1033, A Protein Extract fromLumbricus rubellus, Possesses Antithrombotic and Thrombolytic Activities

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Jessica Trisina ◽  
Febrina Sunardi ◽  
Maggy T. Suhartono ◽  
Raymond R. Tjandrawinata
Keyword(s):  
Ex Vivo ◽  
Blood Clot ◽  
Lumbricus Rubellus ◽  
Clot Lysis ◽  
Ancient Medicine ◽  
Antiplatelet Aggregation ◽  
Medicinal Value ◽  
Thrombolytic Action ◽  
Fibrin Plate ◽  
Long Acting

The medicinal value of earthworm has been widely known since the history of Asian ancient medicine. This present study aims to determine the mechanism of action and effect of a standardized extract ofLumbricus rubellusnamed as DLBS1033. The fibrinogen degradation, antiplatelet aggregation, andex vivoantithrombotic assay using human blood were performed to study antithrombotic activity. Fibrin plate and clot lysis assay were also done to examine thrombolytic properties. DLBS1033 was found to possess fibrinogenolytic activity onα-,β-, andγ-chain of fibrinogen. It also induced antiplatelet aggregation and prolonged blood clotting time, which further confirmed its antithrombotic properties. In addition, thrombolytic properties of DLBS1033 were shown with its fast and long-acting fibrinolytic activity, as well as its effective blood clot lysis activities. In conclusion, DLBS1033 conferred antithrombotic and thrombolytic action which could be used as a safe and promising oral thrombolytic drug.

Cohparison of Variability of Different Methods of Measuring Fibrinolytic Activity

1979 ◽  
Author(s):  
R. Chakrabarti ◽  
S.G. Thompson ◽  
T.W. Meade
Keyword(s):  
Fibrinolytic Activity ◽  
Large Scale ◽  
Blood Clot ◽  
Clot Lysis ◽  
Laboratory Error ◽  
Lysis Time ◽  
Fibrin Plate ◽  
Heart Study ◽  
Euglobulin Lysis Time ◽  
Plate Area

The Northwick Park Heart Study has drawn attention to the variability, especially within-person, of the dilute blood clot lysis time (DBCLT). However, this method has considerable practical advantages in large-scale surveys. The variability of OBCLT has therefore been compared with that of the euglobulin. lysis time (ELT) and the euglobulin fibrin plate area (EFPA). Each measurement has been made 10 times over a 9 month period in each of 12 healthy people; fibrinogen levels have also been measured. As expected, highly significant correlations (r) have been obtained between the three methods: DBCLT and ELT, + 0.63 DBCLT and EFPA, - 0.47; ELT and EFPA, - 0.54 (P<0.001 in each case). The between-pernon variance, distinguishing one person from another, accounts for 60% of the total vnriance in DBCLT, 35% in ELT and 10% in SFPA. For fibrinogen, the value is nearly 90%. The rest of the variance in each case is accounted for by hiological within-person variation and Laboratory error. Thus, while DBCLT is a variable method of determining an individual’s characteristic level of fibrinolytic activity, it is probably lees so than other commonly used methods. The results of this experiment suggest that a previous estimate of the within-person variability of DBCLT (Meade and North, 1977, British Medical Bulletin, 33, 283) may have been too high.

The Measurement of Fibrinolysis in the Rat

1971 ◽  
Vol 26 (02) ◽  
pp. 295-310 ◽  
Author(s):  
M. J Gallimore ◽  
H. M Tyler ◽  
J. T. B Shaw
Keyword(s):  
Whole Blood ◽  
Fibrinolytic Activity ◽  
Factor Xiii ◽  
Degradation Products ◽  
Blood Clot ◽  
Clot Lysis ◽  
Plate Assay ◽  
Fibrin Degradation Products ◽  
Fibrin Plate ◽  
Dilute Blood

SummaryMethods are described for measuring fibrinolytic activity in the rat. These include dilute blood clot lysis, euglobulin clot lysis, a fibrin plate assay with euglobulin solutions, and an accelerated whole blood clot lysis technique in which limited fibrinolysis is induced with urokinase. In addition, methods have been worked out for the estimation of four plasma components closely involved in fibrinolysis: fibrinogen, factor XIII, plasma inhibitors and fibrin degradation products. The sensitivity and validity of the assays were tested by studying their capacity to detect changes resulting from the administration of eledoisin, Neohydrin and turpentine.

The Effect of Plasma Fibrinogen Levels on Measures of Fibrinolytic Activity

1978 ◽  
Vol 39 (02) ◽  
pp. 450-454 ◽  
Author(s):  
R Chakrabarti ◽  
W R S North ◽  
T W Meade
Keyword(s):  
Multiple Regression ◽  
Fibrinolytic Activity ◽  
Blood Clot ◽  
Plasma Fibrinogen ◽  
Clot Lysis ◽  
Lysis Time ◽  
Fibrin Plate ◽  
Plate Area ◽  
Dilute Blood ◽  
Clot Lysis Time

SummaryIt has been claimed that lysis time methods may be inappropriate as measures of fibrinolytic activity on the grounds that they are largely determined by plasma fibrinogen levels. The dilute blood clot lysis time (DBCLT) has therefore been measured in 103 subjects; fibrinolytic activity (expressed as 100/DBCLT) has been compared with the fibrin plate area (FPA) lysed by the euglobulin fraction, the latter method being, of course, virtually independent of plasma fibrinogen. Plasma fibrinogen levels have also been measured; they ranged from 167 to 416 mg%. Results have been analysed by the technique of multiple regression. The incorporation of plasma fibrinogen levels in the regression equation relating 100/DBCLT to FPA does not result in a significant increase in the proportion of the variance in 100/DBCLT that can be explained. It is concluded that there is no evidence that DBCLT is influenced by plasma fibrinogen levels within the physiological range.

Comparison of variability of different methods of measuring fibrinolytic activity

1979 ◽  
Author(s):  
R Chakrabarti ◽  
S Thompson ◽  
T Meade
Keyword(s):  
Fibrinolytic Activity ◽  
Large Scale ◽  
Blood Clot ◽  
Clot Lysis ◽  
Laboratory Error ◽  
Lysis Time ◽  
Fibrin Plate ◽  
Heart Study ◽  
Euglobulin Lysis Time ◽  
Plate Area

The Northwick Park Heart Study has drawn attention to the variability, especially within-person, of the dilute blood clot lysis time (DBCLT). However, this method has considerable practical advantages in large-scale surveys. The variability of DBCLT has therefore been compared with that of the euglobulin lysis time (ELT) and the euglobulin fibrin plate area (EFPA). Each measurement has been made 10 times over a 9 month period in each of 12 healthy people; fibrinogen levels have also been measured. As expected, highly significant correlations (r) have been obtained between the three methods: DBCLT and ELT, + 0.63; DBCLT and EFPA, - 0.47; ELT and EFPA, - 0.54 (P<0.001 in each case). The between-person variance, distinguishing one person from another, accounts for 60% of the total variance in DBCLT, 35% in ELT and 10% in EFPA. For fibrinogen, the value is nearly 90%. The rest of the variance in each case is accounted for by biological within-person variation and laboratory error. Thus, while DBCLT is a variable method of determining an individual’s characteristic level of fibrinolytic activity, it is probably less so than other commonly used methods. The results of this experiment suggest that a previous estimate of the within-person variability of DBCLT (Meade and North, 1977, British Medical Bulletin, 33, 283) may have been too high.

Dependence of Blood Clot Lysis on the Mode of Transport of Urokinase into the Clot - A Magnetic Resonance Imaging Study in Vitro

1991 ◽  
Vol 65 (05) ◽  
pp. 549-552 ◽  
Author(s):  
A Blinc ◽  
G Planinšič ◽  
D Keber ◽  
O Jarh ◽  
G Lahajnar ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Pressure Difference ◽  
Volume Flow Rate ◽  
Blood Clot ◽  
Linear Regression Analysis ◽  
Imaging Study ◽  
Clot Lysis ◽  
Resonance Imaging

SummaryMagnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3 .7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 ± 2.4 × 10−2 ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p <0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.

Design and Evaluation of Long Acting Biodegradable PLGA Microspheres for Ocular Drug Delivery

2019 ◽  
Vol 10 ◽  
Author(s):  
Anjali Pandya ◽  
Rajani Athawale ◽  
Durga Puro ◽  
Geeta Bhagwat
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Degradation Products ◽  
Ex Vivo ◽  
Research Work ◽  
Entrapment Efficiency ◽  
Rational Approach ◽  
Plga Microspheres ◽  
Long Acting

Background: The research work involves development of PLGA biodegradable microspheres loaded with dexamethasome for intraocular delivery. Objective: To design and evaluate long acting PLGA microspheres for ocular delivery of dexamethasone. Method: Present formulation involves the development of long acting dexamethasone loaded microspheres composed of a biodegradable controlled release polymer, Poly(D, L- lactide-co-glycolide) (PLGA), for the treatment of posterior segment eye disorders intravitreally. PLGA with monomer ratio of 50:50 of lactic acid to glycolic acid was used to achieve a drug release up to 45 days. Quality by Design approach was utilized for designing the experiments. Single emulsion solvent evaporation technique along with high pressure homogenization was used to facilitate formation of microspheres. Results: Particle size evaluation, drug content and drug entrapment efficiency were determined for the microspheres. Particle size and morphology was observed using Field Emission Gun-Scanning Electron Microscopy (FEG-SEM) and microspheres were in the size range of 1-5 μm. Assessment of drug release was done using in vitro studies and transretinal permeation was observed by ex vivo studies using goat retinal tissues. Conclusion: Considering the dire need for prolonged therapeutic effect in diseases of the posterior eye, an intravitreal long acting formulation was designed. Use of biodegradable polymer with biocompatible degradation products was a rational approach to achieve this aim. Outcome from present research shows that developed microspheres would provide a long acting drug profile and reduce the frequency of administration thereby improving patient compliance.

scholarly journals Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zuo ◽  
Mark Warnock ◽  
Alyssa Harbaugh ◽  
Srilakshmi Yalavarthi ◽  
Kelsey Gockman ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Ex Vivo ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Bleeding Complications ◽  
Clot Lysis ◽  
Thrombosis Prophylaxis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

AbstractPatients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.

Biochemical and Pharmacological Properties of SANORG 34006, a Potent and Long-Acting Synthetic Pentasaccharide

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4197-4205 ◽  
Author(s):  
J.M. Herbert ◽  
J.P. Hérault ◽  
A. Bernat ◽  
R.G.M. van Amsterdam ◽  
J.C. Lormeau ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Therapeutic Index ◽  
Inhibitory Effect ◽  
Experimental Models ◽  
Treatment And Prevention ◽  
Long Acting

Abstract SANORG 34006 is a new sulfated pentasaccharide obtained by chemical synthesis. It is an analog of the “synthetic pentasaccharide” (SR 90107/ ORG 31540) which represents the antithrombin (AT) binding site of heparin. SANORG 34006 showed a higher affinity to human AT than SR 90107/ORG 31540 (kd = 1.4 ± 0.3 v 48 ± 11 nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT on factor Xa (1,240 ± 15 anti–factor Xa U/mg v850 ± 27 anti-factor Xa U/mg for SR 90107/ORG 31540). In vitro, SANORG 34006 inhibited thrombin generation occurring via both the extrinsic and intrinsic pathway. After intravenous (IV) or subcutaneous (SC) administration to rabbits, SANORG 34006 displayed a long-lasting anti–factor Xa activity and inhibition of thrombin generation (TG) ex vivo. SANORG 34006 was slowly eliminated after IV or SC administration to rats, rabbits, and baboons, showed exceptionally long half-lives (between 9.2 hours in rats and 61.9 hours in baboons), and revealed an SC bioavailability near 100%. SANORG 34006 displayed antithrombotic activity by virtue of its potentiation of the anti–factor Xa activity of AT. It strongly inhibited thrombus formation in experimental models of thromboplastin/stasis-induced venous thrombosis in rats (IV) and rabbits (SC) (ED50values = 40.0 ± 3.4 and 105.0 ± 9.4 nmol/kg, respectively). The duration of its antithrombotic effects closely paralleled the ex vivo anti–factor Xa activity. SANORG 34006 enhanced rt-PA–induced thrombolysis and inhibited accretion of125I-fibrinogen onto a preformed thrombus in the rabbit jugular vein suggesting that concomitant use of SANORG 34006 during rt-PA therapy might be helpful in facilitating thrombolysis and preventing fibrin accretion onto the thrombus under lysis. Contrary to standard heparin, SANORG 34006 did not enhance bleeding in a rabbit ear incision model at a dose that equals 10 times the antithrombotic ED50 in this species and, therefore, exhibited a favorable therapeutic index. We suggest that SANORG 34006 is a promising compound in the treatment and prevention of various thrombotic diseases.

Effect of Heparin on TAFI-Dependent Inhibition of Fibrinolysis: Relative Importance of TAFIa Generated by Clot-Bound and Fluid Phase Thrombin

2002 ◽  
Vol 88 (08) ◽  
pp. 282-287 ◽  
Author(s):  
Anna Pentimone ◽  
Bianca Binetti ◽  
Marialisa Cramarossa ◽  
Donatella Piro ◽  
Nicola Semeraro ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Blood Clot ◽  
Fluid Phase ◽  
Clot Lysis ◽  
Relative Importance ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Dependent Inhibition ◽  
Fibrinolysis Inhibitor ◽  
Dependent Mechanism

SummaryHeparin has been proposed to enhance thrombolysis by inhibiting thrombin-dependent generation of activated TAFI (thrombin activatable fibrinolysis inhibitor), a carboxypeptidase that inhibits fibrinolysis. We evaluated the effect of heparin in an in vitro thrombolysis model consisting of a radiolabelled blood clot submerged in defibrinated plasma. Fibrinolysis was induced by adding t-PA (250 ng/ml) and calcium to the plasma bath. Control experiments indicated that thrombin generation induced by recalcification caused significant TAFI activation and inhibited clot lysis. Heparin (up to 1 U/ml), added to the plasma bath, failed to enhance clot lysis. Thrombin generation in the fluid phase was totally inhibited by heparin at concentrations > 0.5 U/ml. In contrast, thrombin generation on the clot surface was not inhibited by heparin (1 U/ml). TAFIa generation did occur in heparin-containing samples (1 U/ml) and amounted to about 10% of TAFIa formed in control samples. This low amount of TAFIa did exert antifibrinolytic activity as indicated by the observation that the addition of a specific TAFIa inhibitor (PTI) along with heparin enhanced clot lysis. Hirudin (10 µg/ml), at variance with heparin, inhibited clot-bound thrombin and enhanced clot lysis. These data show that heparin is unable to stimulate fibrinolysis through a TAFI-dependent mechanism, most likely because of its inefficiency in inhibiting thrombin generation on the clot surface. Moreover, they suggest that clot-bound thrombin plays a major role in TAFI-mediated inhibition of fibrinolysis through “localized” TAFIa generation.

A Reconstituted Dilute Blood Clot Lysis Assay for the Medium Throughput Screening of Thrombolytic Compounds

1999 ◽  
Vol 270 (1) ◽  
pp. 24-32 ◽  
Author(s):  
Albert P. Gadbut ◽  
John R. Schullek ◽  
Arthur M. Hanel ◽  
David R.E. MacAllan
Keyword(s):  
Blood Clot ◽  
Clot Lysis ◽  
Dilute Blood
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