thromboxane-b2 and Venous-Thrombosis

To determine the effect of ulinastatin on plasma thromboxane B(2) and deep vein thrombosis(DVT) in elderly patients after hip joint replacement.. Eighty ASAI-IIpatients aged 65-81 years undergoing hip joint replacement were randomly divided into 4 groups (n=20): Group U1 (ulinastatin 5 000 U/kg);Group U2 (ulinastatin 10 000 U/kg); Group U3 (ulinastatin 20 000 U/kg); and Group C (the same volume of saline as control).The blood samples were collected at 5 time points: preoperation (T(1)), immediately after the operation (T(2)), 1 d (T(3)), 2 d (T(4)) and 3 d after the operation (T(5)), respectively. Thromboxane B(2) was detected, and DVT was also examined through color Doppler ultrasonography 3 d after the operation.. Compared with T(1), the level of thromboxane B(2) significantly increased in Group C at T(2)-5, in Group U1 at T(2-4), in Group U2 and U3 at T(2) (P<0.01). Compared with Group C, the concentration of thromboxane B(2) decreased in Group U1 at T(2-3), in Group U2 and U3 at T(2-4) (P<0.01). Compared with Group U1, thromboxane B(2) significantly decreased in Group U2 and U3 at T(2-4) (P<0.01).The incidence rate of DVT was 40% in Group C, 10% in Group U1. There was no incidence of DVT in the Group U2 and U3 (P>0.05).. Ulinastatin can inhibit blood thromboxane B(2) level in dose dependent manner and prevent DVT in elderly patients after hip joint replacement.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Female; Glycoproteins; Hip Fractures; Humans; Male; Thromboxane B2; Trypsin Inhibitors; Ultrasonography; Venous Thrombosis

We investigated the production of prostacyclin and thromboxane in pregnant women with a previous venous thromboembolic event before, during and after the use of unfractionated heparin and low molecular weight heparin (dalteparin). Twenty women were studied before starting heparin prophylaxis (before 20 weeks of gestation), during heparin prophylaxis (at 30 weeks of gestation) and after heparin prophylaxis (16 weeks after delivery). Ten pregnant women with no history of thromboembolism were studied as the control group. Urinary output of the stable metabolite of prostacyclin (2,3-dinor-6-keto-PGF1alpha) and that of thromboxane A2 (2,3-dinor-TxB2), as well as a number of markers of thrombophilia were measured and expressed as mean (+/-SEM). Women with a history of thromboembolism were characterized by normal prostacyclin production but elevated thromboxane production (44.0 +/- 4.1 versus 19.0 +/- 3.6 ng/mmol creatinine, P < 0.001) at 12 weeks of pregnancy. Heparin prophylaxis (regardless of the type) had abolished elevated thromboxane concentrations at 30 weeks of gestation. Four months after delivery, thromboxane dominance had returned (25.2 +/- 3.5 versus 13.6 +/- 2.1 ng/mmol creatinine, P < 0.01). The presence of hereditary thrombophilia (9/20) was not associated with any changes in prostanoid concentrations. Thus, women with a history of venous thromboembolic events have thromboxane dominance during and after pregnancy, but this dominance can be eliminated through the use of heparins.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Analysis of Variance; Anticoagulants; Body Mass Index; Case-Control Studies; Dalteparin; Factor V; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Statistics, Nonparametric; Thromboxane B2; Thromboxanes; Venous Thrombosis

To evaluate the rate of thromboxane biosynthesis in patients with systemic lupus erythematosus (SLE), exploring the interplay between antiphospholipid antibodies (aPL) and 2 markers of endothelial perturbation: thrombin generation and platelet activation.. A comparison of 11-dehydrothromboxane B2 (TXB2) excretion, which is a marker of in vivo platelet activation, aPL, von Willebrand factor (vWF) and tissue plasminogen activator (tPA), which are 2 circulating markers of endothelial perturbation, and plasma levels of the prothrombin fragment F1+2, which is a marker of thrombin generation, was performed in 40 SLE patients and 40 healthy subjects. Thromboxane metabolite excretion was also measured in 8 SLE patients before and after treatment with low-dose aspirin.. SLE patients had significantly higher 11-dehydro-TXB2 excretion, plasma F1+2, vWF, and tPA levels than controls. A statistically significant correlation was found between plasma levels of vWF and tPA and excretion of thromboxane metabolite. Moreover, significantly higher 11-dehydro-TXB2 was found in patients with aPL positivity and endothelial perturbation. Low-dose aspirin suppressed 11-dehydro-TXB2 by 80%, suggesting a predominant platelet source of enhanced thromboxane biosynthesis. After a median followup of 48 months, all SLE patients who experienced major cardiovascular events had thromboxane metabolite excretion, aPL positivity, and signs of endothelial perturbation.. We have characterized a sensitive marker of platelet activation, which is abnormal in SLE patients who were positive for aPL and endothelial perturbation. This analytical approach may help identify those patients at increased risk of thrombosis as potential candidates for antiplatelet therapy.

Topics: Adult; Antibodies, Antiphospholipid; Antigens; Aspirin; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Humans; Ischemia; Lupus Erythematosus, Systemic; Male; Middle Aged; Myocardial Infarction; Stroke; Thromboxane B2; Thromboxanes; Tissue Plasminogen Activator; Venous Thrombosis; von Willebrand Factor

The present study was designed to explore the regulatory mechanisms and influences of cotinine on deep vein thrombosis (DVT) in rats via the toll-like receptor 4/nuclear factor κ binding (TLR-4/NF-κB) pathway.. In this experimental study, 30 SD rats were randomly assigned to control group, sham operation group, model group, cotinine (10 μg/kg) group, and model + cotinine (10 μg/kg) group. The thromboxane B2 (TXB2), 6-keto-PGF1α, plasminogen activator inhibitor (PAI), tissue plasminogen activator (t-PA), TLR4, NF-κB, and p65 mRNA and protein expression and tissue changes were analyzed by ELISA, Hematoxylin-Eosin (HE) staining, RT-PCR, and Western blot.. There was no significant difference between the control and sham operation groups (P>0.05). The model and cotinine groups showed significantly higher mRNA and protein levels of TXB2, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), PAI, TLR-4, and NF-κB, and significantly lower levels of 6-keto-PGF1α and t-PA than the control and sham operation groups (P<0.05), and the model + cotinine group showed significantly higher mRNA and protein levels of TXB2, IL-6 and TNF-α, PAI, TLR-4, and NF-κB and significantly lower levels of 6-keto-PGF1α and t-PA than the model group (P<0.05).. Cotinine can aggravate thrombus and inflammation in rats with DVT, and the mechanism may be associated with the activation of the TLR-4/NF-κB inflammatory signaling pathway.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents; Cotinine; Disease Models, Animal; Fibrinolytic Agents; Male; NF-kappa B; Rats, Sprague-Dawley; Signal Transduction; Thromboxane B2; Toll-Like Receptor 4; Venous Thrombosis

Recently, microRNAs (miRNAs) have been demonstrated to play important roles in the cardiovascular system, including heart, blood vessels, plasma, and vascular diseases. Deep vein thrombosis (DVT) refers to the formation of blood clot in the deep veins of the human body and is a common peripheral vascular disease. Herein, we explored the mechanism of miR-9-5p in DVT through nuclear factor-κB (NF-κB). The expression of miR-9-5p in DVT rats was measured through the establishment of DVT rat models, followed by the alteration of miR-9-5p and NF-κB p50 in rats through the injection of constructed lentiviral vectors so as to explore the role of miR-9-5p and NF-κB p50 expression in rats. Next, the expression of NF-κB p50 and levels of inflammation-related factors plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-8 (IL-8) were measured after the injection with lentiviral vectors, followed by the assessment of platelet aggregation and TXB2 content. MiR-9-5p was found to be downregulated in DVT rats. Through dual luciferase reporter gene assay, NF-κB p50 was verified as the target gene of miR-9-5p and miR-9-5p could negatively regulate NF-κB p50. MiR-9-5p over-expression decreased the levels of PAI-1, TNF-α, IL-6, and IL-8 and platelet aggregation as well as TXB2 content, thus inhibiting thrombosis. Meanwhile, over-expressed NF-κB p50 could reverse the anti-inflammatory or anti-thrombotic effect of miR-9-5p. In summary, miR-9-5p over-expression can suppress the NF-κB signaling pathway through p50 downregulation, thus alleviating inflammation and thrombosis in DVT rats. MiR-9-5p could serve as a potential therapeutic target for DVT.

Topics: Animals; Gene Expression Regulation; Inflammation; Interleukin-6; Interleukin-8; MicroRNAs; NF-kappa B p50 Subunit; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Protective Agents; Rats; Thromboxane B2; Tumor Necrosis Factor-alpha; Venous Thrombosis

Cydonia oblonga Miller (COM) is traditionally used in Uyghur medicine for the prevention of cardiovascular disease. The present study is designed to explore the effects of COM extracts on models and markers of thrombosis and related biomarkers.. 20, 40, 80 mg/kg/day COM aqueous extracts and 5mg/kg/day aspirin, orally for 14 days were compared to untreated controls in mice on bleeding and clotting times, using the tail cutting and glass slide methods and for death rates in collagen-epinephrine pulmonary thrombosis, thrombolysis in vitro and euglobulin lysis time (ELT). In rats, common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6-keto-PGF1α) were measured.. Compared to controls, COM extracts dose-dependently prolonged bleeding by 2.17, 2.78 and 3.63 times, vs. aspirin 2.58, and the clotting time by 1.44, 2.47 and 2.48 times, vs. aspirin 1.91. COM reduced pulmonary embolus mortality by 27, 40 and 53%, vs. 47% for aspirin. COM dose-dependently increased thrombolysis by 45, 55 and 63%, vs. 56% for aspirin, and shortened ELT to 71, 61 and 43%, vs. 43% for aspirin. In rats, venous occlusion time was prolonged. Arterial and venous thrombus weights were dose-dependently reduced in COM groups. TXB2 decreased and 6-keto-PGF1α increased with COM and aspirin, with an association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all products, and for occlusion time with COM but not for aspirin.. We confirm the experimental effects of COM on hemostasis and thrombosis. Further exploration of putative clinical effects appear justified.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Coagulation; Cardiovascular Agents; Carotid Artery Thrombosis; Chlorides; Collagen; Epinephrine; Ferric Compounds; Fibrinolysis; Hemostasis; Male; Mice, Inbred ICR; Phytotherapy; Plant Extracts; Plant Leaves; Pulmonary Embolism; Rats, Wistar; Rosaceae; Thromboxane B2; Vena Cava, Inferior; Venous Thrombosis

Danshensu, a type of dihydroxyphenyl lactic acid, is one of the most abundant active phenolic acids in the dried root of Salvia miltiorrhizae (Lamiaceae)--widely used traditional Chinese medicine. The effects of danshensu on platelet aggregation and thrombus formation in rats were examined using various methods. It was found that danshensu significantly reduced thrombus weight in 2 experimental thrombosis models; dose-dependent inhibition of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation occurred in normal and blood stasis-induced rats; Danshensu also significantly mitigated blood viscosity, plasma viscosity and hematocrit levels. Moreover, danshensu significantly inhibited venous thrombosis-induced expression of cyclooxygenases-2 (COX-2) rather than cyclooxygenases-1(COX-1) in the venous walls, down regulated thromboxane B2 (TXB2) and up regulated 6-keto prostaglandin F1α (6-keto-PGF1α), normalizing the TXB2/6-keto-PGF1α ratio. In addition, danshensu did not induce gastric lesions and even had protective effects on aspirin-induced ulcer formation at doses as high as 60 mg/kg. These findings suggest that the antithrombotic and antiplatelet aggregation effects of danshensu are attributed to its highly selective inhibition of COX-2 and ability to normalize the thromboxane A2(TXA2)/prostacyclin(PGI2) balance. These findings suggest that danshensu have great prospects in antithrombotic and antiplatelet therapy.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cyclooxygenase 1; Cyclooxygenase 2; Disease Models, Animal; Lactates; Platelet Aggregation; Rats; Thromboxane A2; Thromboxane B2; Venous Thrombosis

To investigate the effects of Qushuanling Capsule ( QSLC) on thrombus formation and platelet aggregation in rats.. Arteriovenous bypass, venous thrombosis, and middle cerebral artery thrombosis models were used in rats to investigate the anti-thrombotic effects of QSLC, a compound of nine Chinese herbs. The platelet aggregation induced by adenosine diphosphate (ADP), thrombin or arachidonic acid (AA), as well as the contents of thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F1α (6-keto-PGF1α) in rat plasma and aortic walls, were determined to investigate the possible mechanisms of the anti-thrombotic effects of QSLC.. After oral administration with QSLC for 7 days, arteriovenous bypass thrombosis was obviously suppressed compared with the model group, venous thrombosis was also obviously suppressed, rat behaviors were obviously improved, and brain infarct size as well as water content were also reduced. The platelet aggregation induced by ADP or thrombin was inhibited by QSLC, but the drug had no effect on AA-induced platelet aggregation and content of TXB(2) and 6-keto-PGF1α in plasma and the aortic wall.. These results suggest that QSLC can be used in the prevention and treatment of thrombotic diseases, and that its mechanism of action may be related to inhibition of platelet aggregation.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Animals; Aorta; Cerebral Infarction; Drugs, Chinese Herbal; Male; Middle Cerebral Artery; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Thrombosis; Thromboxane B2; Venous Thrombosis

Interleukin-18 (IL-18) is an important proinflammatory cytokine. However, little is known about the roles of IL-18 in the process of venous thrombosis. This study aimed to investigate the roles of IL-18 during deep vein thrombosis (DVT).. Fifty rats were randomly divided into 0 (control group), 12, 24, 36 and 48 h groups (10 rats in each group) by observation time. The inferior vena cava (IVC) was ligated to establish the DVT model. Serum samples were extracted to determine the levels of IL-18, tumor necrosis factor-alpha (TNF-α), thromboxane B2 (TXB2) and 6-keto-prostaglandin Fl alpha (6-keto-PG Flα) by enzyme-linked immunosorbent assay (ELISA). The weight and length of IVC was also measured.. The DVT model was successfully established by ligating IVC. The injury of vein endothelium was observed in the model groups. IL-18, TNF-α, TXB2, TXB2/6-keto-PG Flα levels and thrombus weight were significantly increased in the model groups as compared with the control group, and peaked at 24 h after IVC ligation. 6-keto-PG F1α slightly decreased in the model groups comparing with the control group. IL-18 was positively correlated with TNF-α, TXB2, TXB2/6-keto-PG Flα ratio and thrombus weight. However, IL-18 was negatively correlated with 6-keto-PG Flα. There was a positive correlation between TXB2/6-keto-PG Flα ratio and thrombus weight.. Serum IL-18 level increased in the process of DVT, which might impair venous endothelial cells and result in venous thrombosis. IL-18 might be a new potential therapeutic target of DVT prevention.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Inflammation Mediators; Interleukin-18; Ligation; Male; Rats; Rats, Sprague-Dawley; Thromboxane B2; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation; Vena Cava, Inferior; Venous Thrombosis

The role of prostacyclin in the development of venous thrombosis and vascular dysfunction in humans is unclear. In patients with deep vein thrombosis (DVT, n=34) and controls (matched for age, sex, indexes of systemic inflammation and metabolic status, n=20), we studied (i) differences on systemic markers of vascular disease and platelet activation and (ii) the influence of prostacyclin receptor gene (PTGIR) polymorphisms.. Enhanced levels of urinary 11-dehydro-thromboxane (TX)B2 and plasma [soluble(s)] P-selectin, mostly platelet derived, were detected in DVT patients, whereas plasma von Willebrand factor levels and intima-media thickness of the common carotid arteries were not significantly different. In all patients' cohorts, we identified five PTGIR polymorphisms (three nonsynonymous: P226T, R212C, V196L; two synonymous: V53V, S328S). In the four individuals carriers of R212C polymorphism (three in DVT, one in controls), intima-media thickness values were significantly (P=0.0043) higher than those detected in individuals of all cohorts [1.68+/-0.38, 1.55 (1.4-2.2) vs. 1.05+/-0.33, 1.08 (0.01-1.68) mm, respectively, mean+/-SD, median (range)]. Moreover, enhanced sP-selectin and 11-dehydro-TXB2, in DVT versus controls, were statistically significant only in carriers of both synonymous PTGIR polymorphisms V53V/S328S. Only the PTGIR mutant R212C was dysfunctional when examined in an in vitro overexpression system.. Our results suggest a propensity of enhanced platelet activation in DVT patients with PTGIR polymorphisms V53V/S328S. Moreover, we identified a dysfunctional PTGIR polymorphism (R212C) associated with intimal hyperplasia.

Topics: Adult; Aged; Biomarkers; Female; Genetic Linkage; Genetic Testing; Humans; Hyperplasia; Male; Middle Aged; P-Selectin; Platelet Activation; Polymorphism, Single Nucleotide; Receptors, Epoprostenol; Thromboxane B2; Tunica Intima; Venous Thrombosis

D-003 is a natural mixture of higher primary saturated aliphatic acids purified from sugar cane wax, whose main component is octacosanoic acid followed by triacontanoic, dotriacontanoic, and tetratriacontanoic acids. D-003 inhibits platelet aggregation and arterial thrombosis experimentally induced in a dose-dependent fashion. This study was undertaken to investigate the effects of D-003 (25 and 200 mg/kg) in experimental models of venous thrombosis and on plasma levels of two metabolites from arachidonic acid (AA) : thromboxane A(2) (TxA(2)) and prostacyclin (PgI(2)). D-003 orally administered as single doses of 200 mg/kg, but not at 25 mg/kg, significantly increased plasma levels of 6 keto PgF1alpha levels, a stable metabolite of PgI(2) in PPP obtained from collagen-stimulated blood (4 microg/ml) compared with control group. Nevertheless, levels of 6 keto PgF1alpha levels determined after 10 days of oral treatment with both doses of D-003 were significantly larger than those of the controls. Likewise, single and repeated oral doses of D-003 (25 and 200 g/kg) significantly reduced the TxB(2) and MDA plasma levels obtained from whole blood stimulated by collagen. Hence, TxB(2)/6 keto PgF1alpha ratio significantly decreased in animals treated with D-003. Single and repeated oral doses of D-003 (25 and 200 mg/kg) significantly reduced the weight of venous thrombus experimentally induced in rats. D-003 at single doses (400 mg/kg but not 200 mg/kg) significantly protected from death induced by endovenous infusion of collagen plus epinephrine in mice. The present results support that these effects of D-003 on AA metabolites could explain, at least partially, its antiplatelet and antithrombotic effects.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Arachidonic Acid; Blood Platelets; Collagen; Epinephrine; Fatty Acids; Fibrinolytic Agents; Male; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Saccharum; Statistics, Nonparametric; Survival Analysis; Thromboxane B2; Venous Thrombosis; Waxes