scholarly journals Inhibition of intravascular fibrin deposition by dipyridamole in experimental animals

Blood ◽  
1975 ◽  
Vol 45 (4) ◽  
pp. 569-575
Author(s):  
V Gurewich ◽  
B Lipinski ◽  
R Wetmore
Keyword(s):  
Reticuloendothelial System ◽  
Experimental Models ◽  
Significant Inhibition ◽  
Fibrin Deposition ◽  
Experimental Animals ◽  
Fibrin Monomer

Intravascular fibrin deposition was induced in rabbits by endotoxin, the infusion of fibrin monomer (FM), and by the infusion of thrombin and EACA. A previously developed radioisotope technique was used to measure the fibrin deposits in various organs. Dipyridamole treatment of rabbits caused significant inhibition of fibrin deposition in all three experimental models. The drug also inhibited platelet consumption and, in the thrombin- and EACA-infused animals, fibrinogen consumption as well. The results obtained with dipyridamole were compared with the effect of thorotrast. It was concluded from this comparison that the effect of dipyridamole could not be attributed to inhibition of the reticuloendothelial system. It is postulated that dipyridamole inhibits the final step at which soluble FM is precipitated as fibrin in vivo.

scholarly journals Inhibition of intravascular fibrin deposition by dipyridamole in experimental animals

Blood ◽  
1975 ◽  
Vol 45 (4) ◽  
pp. 569-575 ◽  
Author(s):  
V Gurewich ◽  
B Lipinski ◽  
R Wetmore
Keyword(s):  
Reticuloendothelial System ◽  
Experimental Models ◽  
Significant Inhibition ◽  
Fibrin Deposition ◽  
Experimental Animals ◽  
Fibrin Monomer

Abstract Intravascular fibrin deposition was induced in rabbits by endotoxin, the infusion of fibrin monomer (FM), and by the infusion of thrombin and EACA. A previously developed radioisotope technique was used to measure the fibrin deposits in various organs. Dipyridamole treatment of rabbits caused significant inhibition of fibrin deposition in all three experimental models. The drug also inhibited platelet consumption and, in the thrombin- and EACA-infused animals, fibrinogen consumption as well. The results obtained with dipyridamole were compared with the effect of thorotrast. It was concluded from this comparison that the effect of dipyridamole could not be attributed to inhibition of the reticuloendothelial system. It is postulated that dipyridamole inhibits the final step at which soluble FM is precipitated as fibrin in vivo.

Animal Models in Peritoneal Dialysis Research: A Need for Consensus

2005 ◽  
Vol 25 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Siska Mortier ◽  
Norbert H. Lameire ◽  
An S. De Vriese
Keyword(s):  
Animal Model ◽  
Peritoneal Dialysis ◽  
Animal Models ◽  
Solute Transport ◽  
Experimental Models ◽  
Research Groups ◽  
Experimental Animals ◽  
Collective Effort ◽  
Study Duration

The development of an adequate animal model for peritoneal research remains an object of concern. In vivo peritoneal dialysis (PD) research is hampered by the large variety of available models that make interpretation of results and comparison of studies very difficult. Species and strain of experimental animals, method of peritoneal access, study duration, measures of solute transport and ultrafiltration, and sampling for histology differ substantially among the various research groups. A collective effort to discuss the shortcomings and merits of the different experimental models may lead to a consensus on a standardized animal model of PD.

Effect of bacterial endotoxemia on succinic dehydrogenase of liver and kidney of rabbit

1961 ◽  
Vol 201 (1) ◽  
pp. 16-18 ◽  
Author(s):  
J. Cascarano ◽  
A. D. Rubin ◽  
A. K. Neumann ◽  
B. W. Zweifach
Keyword(s):  
Succinic Dehydrogenase ◽  
Significant Inhibition ◽  
Frozen Sections ◽  
Experimental Animals ◽  
E Coli ◽  
Fresh Frozen ◽  
Tissue Homogenates ◽  
Liver And Kidney ◽  
Lethal Doses

The in vivo inhibition of liver and kidney succinic dehydrogenase by administration of lethal doses of bacterial endotoxin ( Escherichia coli and Salmonella typhosa) was investigated. Quantitative determinations conducted on tissue homogenates revealed significant inhibition of activity only in liver of rabbits injected with E. coli lipopolysaccharide. The histochemical distribution of succinic dehydrogenase in fresh frozen sections of kidney was the same in both control and experimental animals. However, the centrolobular areas of liver appeared considerably depressed in activity in both E. coli and S. typhosa endotoxin-treated animals. These data, along with those presented by other studies in the literature, suggest that the action of endotoxin appears to be restricted to certain cells.

scholarly journals The Fate of Soluble Fibrin Monomer in Relation to Intravascular Fibrin Formation and Degradation in Rabbits

Blood ◽  
1974 ◽  
Vol 44 (5) ◽  
pp. 723-733 ◽  
Author(s):  
Victor Gurewich ◽  
Robert Wetmore ◽  
Andrzej Nowak ◽  
Boguslaw Lipinski
Keyword(s):  
Reticuloendothelial System ◽  
Radioactive Material ◽  
Fibrin Deposition ◽  
Rapid Loss ◽  
Major Pathway ◽  
Fibrin Formation ◽  
Fibrin Monomer ◽  
Subsequent Degradation ◽  
Stabilized Fibrin ◽  
Blood Radioactivity

Abstract 125I-labeled fibrinogen or fibrin monomer (FM) were infused into rabbits, and the radioactivity in the blood, certain organs, and urine was followed. In the FM rabbits, a progressive, relatively rapid loss of blood radioactivity occurred which was accompanied by radioactive deposits in the organs and the excretion of radioactivity in the urine. Extraction of radioactive material from homogenized organ tissues of FM-infused rabbits showed that most of it had the characteristics of stabilized fibrin. Administration of EACA did not change any of the measurements in the fibrinogen animals but increased the rate and extent of fibrin deposition in the FM animals. In animals made leukopenic with HN2, fibrin deposition was inhibited. The findings indicate that a major pathway of FM clearance from the blood involves fibrin formation and deposition with subsequent degradation and excretion. The reticuloendothelial system appeared to play a major role in FM clearance, since most of the fibrin deposits were found in the liver, and the highest concentration was in the spleen. A nonenzymatic mechanism of fibrin formation from soluble FM involving leukocytes is postulated.

scholarly journals Evaluation of Antiepileptic Effect of Cleome viscosa Linn. Leaves Extract in Experimental Animals

2021 ◽  
pp. 35-43
Author(s):  
Manish Kumar Shakya ◽  
Arif Naseer ◽  
Ranjit Singh
Keyword(s):  
Research Work ◽  
Significant Inhibition ◽  
Screening Methods ◽  
Maximal Electroshock ◽  
Significant Delay ◽  
Experimental Animals ◽  
Soxhlet Apparatus ◽  
Cleome Viscosa

Aim: The purpose of this study was to assess the antiepileptic effect of Cleome viscosa Linn. leaves extract in experimental animals. Study Design: The extraction process, acute toxicity study was determined using OECD guidelines, Priliminary phytochemical screening, Antiepileptic pharmacological screening methods and statistical analysis. Place and Duration of Study: The research work was conducted during 10 Jan. 2020 to 10 July 2020 at Dept. of Pharmacology, Rajiv academy for Pharmacy, Mathura (U.P), 281001, India. Methodology: The fresh leaves were shade dried and reduced in size to powder and extracted by soxhlet apparatus. The MECV, CECV and AECV were prepared and subjected to comparative phytochemical profiling for in-vitro analysis. Further the in-vivo screening models like maximal electroshock induced seizures (MES), picrotoxin (PTX) and pentylenetetrazole (PTZ) induced models are used to assess the anti-epileptic effects of the methanol, chloroform and aqueous extracts of Cleome viscosa. Results: The extracts were subjected to phytochemical tests and the carbohydrate, tannins, alkaloids, saponins, flavonoids, steroids and glycosides were found to be present. In the MES induced seizures, MECV (200 mg/kg) showed high significant inhibition on tonic hind limb extension (THLE) (9.33±0.33***), decrease in duration of stupor period (145.2 ± 2.59***) and decreased mortality significantly. In PTX induced model, MECV (200 mg/kg) showed high significant delay on the onset of convulsions (18.00±0.63***), decreased duration of convulsion (3.50 ± 0.18***) and decreased mortality significantly. In PTZ induced model, MECV and AECV (200mg/kg) showed high significant delay on the onset of convulsions (2.55 ± 0.10***), (2.50 ± 0.18***), decreased duration of convulsion (3.67 ± 0.11***), (4.33 ± 0.17**) and decreased mortality significantly. Conclusion: It is clear from the preceding that Cleome viscosa has antiepileptic properties.

The Effect of the Fibrinogen Concentration and the Leukocyte Count on Intravascular Fibrin Deposition from Soluble Fibrin Monomer Complexes

1976 ◽  
Vol 36 (03) ◽  
pp. 605-614 ◽  
Author(s):  
Victor Gurewich ◽  
Boguslaw Lipinski ◽  
Elisabeth Hyde
Keyword(s):  
Fibrinogen Level ◽  
Leukocyte Count ◽  
Inverse Correlation ◽  
Inhibitory Effect ◽  
Fibrinogen Concentration ◽  
Fibrin Deposition ◽  
Fibrin Formation ◽  
Fibrin Monomer

SummaryFibrin formation from fibrin monomer (FM) complexes was studied in experimental animals utilizing a previously described technique for quantitating fibrin deposition. A uniform thrombin infusion was used to produce FM, fibrinolysis being inhibited by EACA. In vivo complex formation between FM and 125I-fibrinogen was demonstrated chromatographically. A direct correlation was found between blood fibrinogen concentration and fibrin deposition in organs. By contrast, an inverse correlation between fibrinogen concentration and both enzymatic or non-enzymatic fibrin formation was found in vitro. The mechanism by which fibrinogen potentiates FM precipitation in vivo could not be explained by coprecipitation of fibrinogen in the complex which could not be demonstrated. The inhibitory effect of HN2 on fibrin deposition despite the associated hyperfibrinogemia induced by this drug is believed to underscore the importance of leukocytes in certain types of fibrin deposition. A correlation between the leukocyte count and fibrin formation from FM was also found. It was concluded that the risk of intravascular fibrin deposition is increased by a raised fibrinogen level especially when accompanied by leukocytosis.

Accumulation of Macromolecular Particles in the Reticuloendothelial System (RES) Mediated by Platelet Aggregation and Disaggregation

1969 ◽  
Vol 22 (03) ◽  
pp. 496-507 ◽  
Author(s):  
W.G van Aken ◽  
J Vreeken
Keyword(s):  
Platelet Aggregation ◽  
Degradation Products ◽  
Reticuloendothelial System ◽  
Caproic Acid ◽  
Carbon Particles ◽  
Carbon Clearance ◽  
Aggregation And Disaggregation ◽  
Platelet Aggregates

SummaryCarbon particles cause platelet aggregation in vitro and in vivo. Prior studies established that substances which modify thrombocyte aggregation also influence the rate at which carbon is cleared from the blood.This study was performed in order to elucidate the mechanism by which the carbon-platelet aggregates specifically accumulate in the RES.Activation of fibrinolysis by urokinase or streptokinase reduced the carbon clearance rate, probably due to generated fibrinogen degradation products (FDP). Isolated FDP decreased the carbon clearance and caused disaggregation of platelets and particles in vitro. Inhibition of fibrinolysis by epsilon-amino-caproic acid (EACA), initially accelerated the disappearance of carbon and caused particle accumulation outside the RES, predominantly in the lungs. It is supposed that platelet aggregation and locally activated fibrinolysis act together in the clearance of particles. In the normal situation the RES with its well known low fibrinolytic activity, becomes the receptor of the particles.

Anti-thrombotic Effect of a PAI-1 Inhibitor in Rats Given Endotoxin

1996 ◽  
Vol 75 (01) ◽  
pp. 118-126 ◽  
Author(s):  
T Abrahamsson ◽  
V Nerme ◽  
M Strömqvist ◽  
B Åkerblom ◽  
A Legnehed ◽  
...  
Keyword(s):  
Plasminogen Activator Inhibitor ◽  
Rat Plasma ◽  
Clot Lysis ◽  
Fibrin Deposition ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fab Fragment ◽  
Dose Dependent Decrease ◽  
Pai 1

SummaryThe aim of this study was to investigate the anti-thrombotic effects of an inhibitor of the plasminogen activator inhibitor-1 (PAI-1) in rats given endotoxin. In studies in vitro, PRAP-1, a Fab-fragment of a polyclonal antibody against human PAI-1, was shown to inhibit PAI-1 activity in rat plasma as well as to stimulate clot-lysis of the euglobulin fraction derived from rat plasma. Endotoxin administered to anaesthetised rats produced a marked increase in plasma PAI-1 activity. To study fibrin formation and lysis in vivo after intravenous (i. v.) injection of the coagulant enzyme batroxobin, 125I-fibrinogen was administered to the animals. The thrombi formed by batroxobin were rapidly lysed in control animals, while the rate of lysis was markedly attenuated in rats given endotoxin. PRAP-1 was administered i.v. (bolus + infusion) to rats given endotoxin and batroxobin and the PAI-1 inhibitor caused a dose-dependent decrease in the 125I-fibrin deposition in the lungs. An immunohistochemical technique was used to confirm this decrease in density of fibrin clots in the tissue. Furthermore, PRAP-1 decreased plasma PAI-1 activity in the rats and this reduction was correlated to the decrease in lung 125I-fibrin deposition at the corresponding time point. It is concluded that in this experimental model the PAI-1 antibody PRAP-1 may indeed inhibit thrombosis in animals exposed to endotoxin.

The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

1993 ◽  
Vol 69 (01) ◽  
pp. 021-024 ◽  
Author(s):  
Shawn Tinlin ◽  
Sandra Webster ◽  
Alan R Giles
Keyword(s):  
Factor Viii ◽  
Canine Model ◽  
Significant Inhibition ◽  
Human Condition ◽  
Haemophilia A ◽  
Variable Expression ◽  
The Family ◽  
Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

Comparison of Immunological and Functional Assays for Measurement of Soluble Fibrin

1995 ◽  
Vol 74 (02) ◽  
pp. 673-679 ◽  
Author(s):  
C E Dempfle ◽  
S A Pfitzner ◽  
M Dollman ◽  
K Huck ◽  
G Stehle ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Low Grade ◽  
Plasma Samples ◽  
Normal Range ◽  
Soluble Fibrin ◽  
Discriminating Power ◽  
Fibrin Monomer ◽  
Cerebral Ischemic

SummaryVarious assays have been developed for quantitation of soluble fibrin or fibrin monomer in clinical plasma samples, since this parameter directly reflects in vivo thrombin action on fibrinogen. Using plasma samples from healthy blood donors, patients with cerebral ischemic insult, patients with septicemia, and patients with venous thrombosis, we compared two immunologic tests using monoclonal antibodies against fibrin-specific neo-epitopes, and two functional tests based on the cofactor activity of soluble fibrin complexes in tPA-induced plasminogen activation. Test A (Enzymun®-Test FM) showed the best discriminating power among normal range and pathological samples. Test B (Fibrinostika® soluble fibrin) clearly separated normal range from pathological samples, but failed to discriminate among samples from patients with low grade coagulation activation in septicemia, and massive activation in venous thrombosis. Functional test C (Fibrin monomer test Behring) displayed good discriminating power between normal and pathological range samples, and correlated with test A (r = 0.61), whereas assay D (Coa-Set® Fibrin monomer) showed little discriminating power at values below 10 μg/ml and little correlation with other assays. Standardization of assays will require further characterization of analytes detected.

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