scholarly journals Clotting activity of camphene derivatives

2015 ◽  
Vol 96 (3) ◽  
pp. 455-458 ◽  
Author(s):  
A A Rakhmatullina ◽  
R G Turaev ◽  
S V Kiselev ◽  
L E Nikitina ◽  
A V Bodrov
Keyword(s):  
Anticoagulant Activity ◽  
Catalyst Activity ◽  
Venous Blood ◽  
Adenosine Diphosphate ◽  
Human Blood Plasma ◽  
Clotting Factors ◽  
13C Nuclear Magnetic Resonance ◽  
Derivatives Of ◽  
Sulfur Containing

Aim. To study of the influence of new synthetized sulfur-containing derivatives of camphene on the thrombocytes aggregating ability and clotting activity of human blood plasma in vitro. Methods. Sulfides and sulphones of camphene were synthesized by thiols electrophilic addition reaction. The structures of the synthetized compounds were clarified by using of 1H and 13C nuclear magnetic resonance, chromato-mass spectrometry and X-ray analysis. Clotting activity of the synthetized compounds was assessed by studying the spontaneous platelet aggregation and plasma coagulating activity of the venous blood of patients with ischemic heart disease. The induced platelets aggregation was studied on plasma obtained from healthy donors. Results. The synthetized compounds demonstrated anti-aggregating and anti-coagulating activity: they inhibited spontaneous and induced thrombocyte aggregation as well as reduced coagulating ability of human plasma. Both camphene sulphone and mainly camphene sulfide (in contrast with acetylsalicylic acid and clopidogrel) totally inhibited thrombocytes aggregation induced by adrenaline, adenosine diphosphate, collagen and arachidonic acid, and decreased the influence of ristocetin. Anticoagulant activity of the synthetized substances is associated to their potential to inhibit thrombocyte activation and to reduce the catalyst activity of phospholipid surface participating in coagulating complexes and clotting factors formation. Conclusion. Low toxicity of terpenoids together with discovered anticoagulant activity of sulfur-containing derivatives of camphene revealing the promising potential of these drugs for further development of novel medical treatments for treating and prevention of different types of thrombophilia.

Maternal and Fetal Platelet Responses and Adrenoceptor Binding Characteristics

1985 ◽  
Vol 53 (01) ◽  
pp. 095-098 ◽  
Author(s):  
C R Jones ◽  
R McCabe ◽  
C A Hamilton ◽  
J L Reid
Keyword(s):  
Adenylate Cyclase ◽  
Venous Blood ◽  
Adenosine Diphosphate ◽  
Binding Characteristics ◽  
Receptor Coupling ◽  
Threshold Response ◽  
Alpha Receptors ◽  
Maternal Responses ◽  
Epidural Anaesthetic

SummaryPaired blood samples were obtained from mothers (venous) and babies (cord venous blood) at the time of delivery by caesarean section under epidural anaesthetic. Fetal platelets failed to aggregate in response to adrenaline in vitro although adrenaline could potentiate the threshold response to adenosine diphosphate (1 μM). Fetal platelet responses to collagen and 8 Arg vasopressin did not differ significantly from maternal responses. Maternal and fetal platelets also showed similar inhibition of aggregation after activation of adenylate cyclase (PGE1 and parathormone), in contrast to the inhibition of adenylate cyclase by adrenaline.Alpha2 adrenoceptors were investigated using [3H] yohimbine binding receptor number and were reduced modestly but significantly on fetal compared to maternal platelets. The failure of fetal platelet aggregation in response to adrenaline appears to be related to a failure of receptor coupling and may represent a delayed maturation of fetal platelet alpha receptors or a response- to increased circulating catecholamines during birth.

In vitro effects of human neutrophil cathepsin G on thrombin generation: Both acceleration and decreased potential

2010 ◽  
Vol 104 (09) ◽  
pp. 514-522 ◽  
Author(s):  
Thomas Lecompte ◽  
Agnès Tournier ◽  
Lise Morlon ◽  
Monique Marchand-Arvier ◽  
Claude Vigneron ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Thrombin Generation ◽  
Time Course ◽  
Anticoagulant Activity ◽  
Cathepsin G ◽  
Coagulation Cascade ◽  
Clotting Factor ◽  
Factor V ◽  
Clotting Factors

SummaryCathepsin G (Cath G), a serine-protease found in neutrophils, has been reported to have effects that could either facilitate or impede coagulation. Thrombin generation (CAT method) was chosen to study its overall effect on the process, at a plasma concentration (240 nM) observed after neutrophil activation. Coagulation was triggered by tissue factor in the presence of platelets or phospholipid vesicles. To help identify potential targets of Cath G, plasma depleted of clotting factors or of inhibitors was used. Cath G induced a puzzling combination of two diverging effects of varying intensities depending on the phospholipid surface provided: accelerating the process under the three conditions (shortened clotting time by up to 30%), and impeding the process during the same thrombin generation time-course since thrombin peak and ETP (total thrombin potential) were decreased, up to 45% and 12%, respectively, suggestive of deficient prothrombinase. This is consistent with Cath G working on at least two targets in the coagulation cascade. Our data indicate that coagulation acceleration can be attributed neither to platelet activation and nor to activation of a clotting factor. When TFPI (tissue factor pathway inhibitor) was absent, no effect on lag time was observed and the anticoagulant activity of TFPI was decreased in the presence of Cath G. Consistent with the literature and the hypothesis of deficient prothrombinase, experiments using Russel’s Viper Venom indicate that the anticoagulant effect can be attributed to a deleterious effect on factor V. The clinical relevance of these findings deserves to be studied.

scholarly journals Do patients with thromboembolic disease have circulating platelet aggregates?

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 205-209 ◽  
Author(s):  
FH Kohanna ◽  
MH Smith ◽  
EW Salzman
Keyword(s):  
Platelet Rich Plasma ◽  
Venous Blood ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Thromboembolic Disease ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Lower Ratio

Reports of circulating platelet aggregates (ie, microemboli) in thromboembolism and other vascular disorders are based on a method (Wu and Hoak , 1974) in which venous blood is collected via scalp vein needle and tubing into either formaldehyde, which fixes aggregates, or EDTA, which disperses them. The ratio of platelet counts in platelet- rich plasma (PRP) from the two blood samples after centrifugation is interpreted as a measure of platelet aggregates in the circulation in vivo. We compared this standard Wu and Hoak technique with a modified one, in which blood was drawn directly into a syringe, and with a third method that avoided centrifugation by counting single platelets in whole blood. Both modified techniques could detect aggregates generated in vitro with adenosine diphosphate (ADP). In 12 normal subjects, the three methods were equivalent, but in 37 patients with thromboembolic disorders, the standard Wu and Hoak method gave a lower ratio than the other methods. Similar results were found in a subset of eight patients with myocardial infarction. Heparin treatment of patients did not influence the results. The data suggest that formation of platelet aggregates occurred during venipuncture. Platelets may be hyperactive in patients with thromboembolic disease and may form aggregates in vitro during collection, but the concept of chronic microembolism in such patients should be reassessed.

scholarly journals Effect of Low Concentrations of Prostacyclin on Platelet Function in Vitro

1997 ◽  
Vol 25 (4) ◽  
pp. 343-346 ◽  
Author(s):  
P. V. Van Heerden ◽  
N. M. Gibbs ◽  
N. Michalopoulos
Keyword(s):  
Platelet Aggregation ◽  
Entire Range ◽  
Venous Blood ◽  
Maximum Amplitude ◽  
Adenosine Diphosphate ◽  
Systemic Circulation ◽  
Direct Effects ◽  
Low Concentrations ◽  
Platelet Aggregation Defect

The study was performed to determine the possible direct effects of low concentrations of prostacyclin that might spill over into the systemic circulation during the administration of inhaled aerosolized prostacyclin. Platelet aggregation in response to adenosine diphosphate and collagen, as well as measurement of the maximum amplitude of the thrombelastograph (TEG), was undertaken in vitro using venous blood exposed to low concentrations of prostacyclin (0, 10, 100 and 500 pg/ml) from eight healthy volunteers. There were statistically significant reductions in parameters of platelet aggregation in response to the agonists adenosine diphosphate (1 μmol/l and 8 μmol/l) and collagen (10 μmol/l) following exposure to as little as 10 pg/ml of prostacyclin. The maximum amplitude of the TEG was unchanged over the entire range of prostacyclin concentrations studied. The results indicate that low concentrations of prostacyclin or prostacyclin metabolite such as may be observed during inhaled aerosolized prostacyclin therapy are likely to be associated with a marked platelet aggregation defect. This defect was not detected by the TEG.

scholarly journals Pathogenetic approach to venous thrombosis markers examination

2013 ◽  
Vol 94 (5) ◽  
pp. 685-691 ◽  
Author(s):  
L D Zubairova ◽  
I G Mustafin ◽  
R M Nabiullina
Keyword(s):  
Blood Flow ◽  
Venous Thrombosis ◽  
Tissue Factor ◽  
Blood Coagulation ◽  
Blood Platelets ◽  
Anticoagulant Activity ◽  
Venous Blood ◽  
Local Concentration ◽  
Clotting Factors ◽  
Blood Constituents

The review summarizes experimental and clinical findings decrypting the mechanisms that initiate venous thrombosis. It is still relevant to consider the pathogenesis of venous thrombosis within the frames of the classic Virchow’s triad, and the mechanisms of interrelation of its separate mechanisms - changes in blood composition, blood flow, or alterations of the blood vessel wall - becomes more clear. Changes in the blood constituents include the amount and functional state of proteins and hemostasis system cells. Among the important changes in blood flow are blood flow rate, affecting the cells and coagulation proteins transport to the site and from the site of thrombosis, and the local shear stress, modulating adhesion and procoagulant activity of endothelium and platelets. Vascular wall provides tissue factor, which is the initiator of blood coagulation; phospholipid surface of cell membranes and microvesicles for assembling coagulation enzyme complexes, as well as adhesion proteins for the blood platelets and leukocytes «capturing». Decreased venous blood outflow and stasis, causing the local hypoxia, are associated with procoagulant changes in blood cells: the expression of P-selectin on endothelium increases, leading to the accumulation of leukocytes and cell microvesicles containing the initiator of blood coagulation - tissue factor. The local concentration of activated clotting factors increases, which along with anticoagulant activity alterations initiates progressing fibrin formation and thrombogenesis. Marking out the key mechanisms allows using them as the potential markers for diagnosing venous thrombosis risk. Among them are cell derived microparticles, cytokines, P-selectin that are investigated as possible indicators of deep vein, pulmonary, cancer associated thrombosis.

THE EFFECT OF THE VENOM OF THE ORIENTAL HORNET ON COAGULATION FACTORS

1987 ◽  
Author(s):  
A Kornberg ◽  
S Kaufman ◽  
L Silber ◽  
J Ishay
Keyword(s):  
Human Plasma ◽  
Degradation Products ◽  
Anticoagulant Activity ◽  
Coagulation Factors ◽  
Plasma Fibrinogen ◽  
Thrombin Time ◽  
Clotting Factors ◽  
Viii And Ix

The extract from the venom sac of Vespa orientalis (VSE) inactivates exogenous and endogenous thromboplastin (Joshua and Ishay, Toxicon, 13:11-20,1975). The prolongation of both prothrombin time (PT) and recalcification time suggests inactivation of other factors. The aim of the present study is to investigate the effect of VSE on clotting factors. A lyophilized VSE with protein concentration of 5 mg/ml was used. Studies were performed in vitro with human plasma and in vivo in cats. Routine methods were employed for the assay of PT, activated tissue thromboplastin (APTT), thrombin time (TT), fibrinogen degradation products (FDP), fibrinogen and factors V,VII,VIII,IX,X. Human plasma was incubated with various concentrations of VSE (0,1,5,10,50,100 μg/ml) for 60 min and for various incubation times (0,5,15,30,+ 60,90,120 min) with 50 μg/ml VSE (n=8). 1 μg/ml VSE prolonged PT from 13.5 to 16 sec (p<0.05) and APTT from 62 to 180 sec. PT was maximal (17.7 sec) with 10 μg/ml and APTT (442 sec) with 50 μg/ml VSE. Factors V,VII,X decreased gradually from 94-105% to 11%,11% and 29% with 100 μg/ml VSE and VIII and IX to 1% even with 1 μg/ml VSE. After 5 min with constant concentration of VSE (50 μg/ml) PT was 14.9 sec (normal 13 sec) and APTT 165 sec (normal 54 sec). Both were maximal (17.5 and 298 sec) after 60 min. Factors VII and X decreased to 13% and 32% and VIII and IX to >1% after 60 min of incubation. Injection of 5 mg/kg VSE to cats (n=6-8) resulted in prolongation of PT from 9.4 to 11.2 sec and of APTT from 19.5 to 63 sec after 5 min. Both were maximal after 90 min (12.3 and 127 sec). Factors V,VII and X decreased from 100% to 7.6%, 13% and 37% and VIII and IX to 1% after 10 min. In all experiments TT and plasma fibrinogen were not affected and FDP were normal. Heating of VSE for 5 min at 80°C abolished completely the anticoagulant activity but dialysis for 24 hr at 4°C had no effect on it. The activity was eluted on Sephadex-25 both in void and post void volumes. The results show that VSE has a potent anticoagulant activity against various factors. Factors VIII and IX are markedly decreased. The effect on V, VII and X is moderate. Plasma fibrinogen is not affected. The nature and clinical significance of the anticoagulant activity merit further investigation.

scholarly journals Synthesis, Docking, and In Vitro Anticoagulant Activity Assay of Hybrid Derivatives of Pyrrolo[3,2,1-ij]Quinolin-2(1H)-one as New Inhibitors of Factor Xa and Factor XIa

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1889 ◽  
Author(s):  
Nadezhda Novichikhina ◽  
Ivan Ilin ◽  
Anna Tashchilova ◽  
Alexey Sulimov ◽  
Danil Kutov ◽  
...  
Keyword(s):  
Anticoagulant Activity ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Protein Targets ◽  
Ic50 Value ◽  
Anticoagulant Drugs ◽  
Factor Xia ◽  
Derivatives Of

Coagulation factor Xa and factor XIa are proven to be convenient and crucial protein targets for treatment for thrombotic disorders and thereby their inhibitors can serve as effective anticoagulant drugs. In the present work, we focused on the structure–activity relationships of derivatives of pyrrolo[3,2,1-ij]quinolin-2(1H)-one and an evaluation of their activity against factor Xa and factor XIa. For this, docking-guided synthesis of nine compounds based on pyrrolo[3,2,1-ij]quinolin-2(1H)-one was carried out. For the synthesis of new hybrid hydropyrrolo[3,2,1-ij]quinolin-2(1H)-one derivatives, we used convenient structural modification of both the tetrahydro- and dihydroquinoline moiety by varying the substituents at the C6,8,9 positions. In vitro testing revealed that four derivatives were able to inhibit both coagulation factors and three compounds were selective factor XIa inhibitors. An IC50 value of 3.68 μM for was found for the best factor Xa inhibitor and 2 μM for the best factor XIa inhibitor.

scholarly journals Novel Pharmacological Properties of Dinoponera quadriceps Giant Ant Venom

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Juliana da Costa Madeira ◽  
Yves Patric Quinet ◽  
Dayanne Terra Tenório Nonato ◽  
Paloma Leão Sousa ◽  
Edna Maria Camelo Chaves ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Anticoagulant Activity ◽  
Adenosine Diphosphate ◽  
South American ◽  
Crude Venom ◽  
Leucocyte Migration ◽  
Ant Venom ◽  
Hymenopteran Species ◽  
Anti Inflammatory

The South American giant ant, Dinoponera quadriceps (Hymenoptera, Formicidae, Ponerinae), produces proteinaceous venom that has antinociceptive, neuroprotective and antimicrobial effects, thereby supporting the popular use of these ants to treat asthma, rheumatism, earache and back pain. Anticoagulant activity is another biological property that has been shown for the venom of other hymenopteran species, like wasps. The aim of this study was to assess the anti-inflammatory, anticoagulant and antiplatelet properties of D. quadriceps venom (DqV). DqV anti-inflammatory activity was assessed by intravenous administration in Swiss mice in the models of paw edema and peritonitis. In vitro, DqV was assessed in coagulation (activated partial thromboplastin time) and platelet aggregation tests. DqV inhibited (27–33%) the edema elicited by carrageenan and the leucocyte migration (43%) elicited by zymosan. DqV decreased by 57% and 42%, respectively, the content of malondialdehyde and nitrite in the peritoneal fluid. DqV prolonged (1.8x) the clotting time and decreased (27%) the platelet aggregation induced by adenosine diphosphate. The crude venom of D. quadriceps presents an anti-inflammatory effect in mice and in vitro anticoagulant and antiplatelet effects.

scholarly journals 277 ANTICOAGULANT ACTIVITY OF ALLIUM ACCESSIONS

HortScience ◽  
1994 ◽  
Vol 29 (5) ◽  
pp. 469f-469
Author(s):  
I.L. Goldman ◽  
B.R Schwartz
Keyword(s):  
Platelet Aggregation ◽  
Anticoagulant Activity ◽  
Calculated Data ◽  
Clotting Factors ◽  
Aggregation Assay ◽  
Inhibition Of Platelet Aggregation ◽  
The Past ◽  
Platelet Aggregation Assay ◽  
Relative Inhibition

In the past twenty years, the presence of blood anticoagulants in plants has been confirmed by a range of clinical and in vitro investigations. The presence of anti-clotting factors in plants presents a unique opportunity for dietary enhancement of circularion and fibrinolysis. Experiments were conducted to assess variability in anticoagulant activity of a range of Allium wild species and cultivated accessions. Anticoagulant activity was determined via a platelet aggregation assay with human plasma. Extracts were prepared from 19 Allium species accessions and 24 cultivated accessions of Allium cepa, including standard inbred lines and open-pollinated popularions. Relative inhibition of platelet aggregation was measured for each accession and inhibition constants (IC50) were calculated. Data from this investigation dcmonstrate large IC50 variability among accessions. Larger IC50 differences (up to 45-fold) were measured among A. cepa accessions than among Allium species accessions (up to 16-fold). Yellow storagc-type A. cepa accessions exhibited the strongest inhibitory activity. Implications of these findings to onion breeding and platelet function will be presented.

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