Crocetin, a carotenoid from Gardenia jasminoides Ellis, protects against hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats.

Crocetin is a natural carotenoid dicarboxylic acid that is found in the fruit of Gardenia jasminoides Ellis (Cape Jasmine) and in the stamen and pistil of Crocus sativus L. (saffron). It is used worldwide as an important spice, food colorant, and herbal medicine.

Mode of action associated with development of hemangiosarcoma in mice given pregabalin and assessment of human relevance.

Pregabalin increased the incidence of hemangiosarcomas in carcinogenicity studies of 2-year mice but was not tumorigenic in rats. Serum bicarbonate increased within 24 h of pregabalin administration in mice and rats. Rats compensated appropriately, but mice developed metabolic alkalosis and increased blood pH.

Preventive effects of hesperidin, glucosyl hesperidin and naringin on hypertension and cerebral thrombosis in stroke-prone spontaneously hypertensive rats.

The effects of hesperidin, glucosyl hesperidin (G-hesperidin), a water-soluble derivative of hesperidin, and naringin on blood pressure and cerebral thrombosis were investigated using stroke-prone spontaneously hypertensive rats (SHRSP). Hesperidin, G-hesperidin and naringin were mixed with diet and fed to the animals for 4 weeks. No effect was evident on body weight, but the supplements significantly suppressed the age related increase in blood pressure.

Astaxanthin inhibits thrombosis in cerebral vessels of stroke-prone spontaneously hypertensive rats.

It is known that vitamin E and some carotenoids have antioxidant activities that alleviate endothelial dysfunction and play a protective role against cardiovascular disease. The current study was designed to examine the hypothesis that astaxanthin, a red pigment carotenoid found in salmonid and crustacean aquaculture, protects stroke-prone spontaneously hypertensive rats (SHRSP) from vascular oxidative damage, hypertension, and cerebral thrombosis. Male 6-week-old SHRSP were classified into 4 groups: a control group, 2 astaxanthin groups, and a vitamin E group.

Hemostatic treatment using factor VIII concentrates for neutralizing high-responding inhibitors prior to CVAD insertion for immune-tolerance induction therapy.

We have utilized high-dose factor VIII (FVIII) concentrates in 4 hemophilia A patients with inhibitors prior to surgery for the insertion of a central venous access device. In total, 3 patients out of 4 had high responding inhibitors. Dosing algorithms for this type of therapy have not been previously validated and established.

Impaired endothelial function may be due to decreased aortic tetrahydrobiopterin, assessed by a new flow-mediated vasodilation in vivo in hypercholesterolemic/atherogenic mice.

Tetrahydrobiopterin (BH4) is an important cofactor for endothelial nitric oxide synthase activity. The relationship between endothelial function in vivo and aortic BH4 level is not fully understood, however. In the present study, we aimed to clarify whether reduction of aortic BH4 levels contributes to endothelial dysfunction in vivo using spontaneously hyperlipidemic mice.

The antithrombotic effects of carrot filtrates in rats and mice.

The prevention of arterial thrombotic disease has a high priority in developed countries. An inappropriate diet is known to enhance the risk for acute thrombotic events and a regular diet with proven antithrombotic effects might be a beneficial way to prevent disease. The present study was undertaken as a part of a series of investigations to examine vegetables and fruits for antithrombotic activity.

Identification of a thrombin-interactive site within the FVIII A2 domain that is responsible for the cleavage at Arg372.

FVIII is activated by cleavage at Arg(372), Arg(740), and Arg(1689) by thrombin. This study showed that an anti-A2 monoclonal antibody, with a specific epitope for residues 484-509, and anti-FVIII inhibitor alloantibodies with similar A2 epitopes, inhibited thrombin-catalyzed FVIII activation. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis showed that cleavage at Arg(372) but not at Arg(740) occurred at approximately fourfold decreased rate in the presence of anti-A2 antibody.

Relationship between the binding sites for von Willebrand factor, phospholipid, and human factor VIII C2 inhibitor alloantibodies within the factor VIII C2 domain.

Some factor VIII (FVIII) inhibitor alloantibodies block FVIII binding to von Willebrand factor (VWF) and phospholipid (PL) and recognize a C2 domain epitope that overlaps both binding sites. We previously showed that FVIII peptide 2315-2330 neutralized FVIII inhibitors and that Cys2326 and Glu2327 contributed to the maximum neutralizing effect. In the present study, we investigated the relationship between the essential binding sites for VWF, PL, and anti-C2 inhibitors by means of competitive-inhibition assays with overlapping synthetic peptides that span the C terminus of the C2 domain (residues 2288-2332).

Heparin-induced inhibitory effects of a prothrombin complex concentrate on global tests of haemostasis.

Prothrombin complex concentrates (PCC) have been used as bypassing agents for the treatment of haemophilia A patients with inhibitor as well as for replacement therapy in congenital and acquired deficiencies of vitamin-K-dependent clotting factors. The efficacy of PCC is variable, however, especially during long-term and high-dose use, and all currently available products of this nature contain heparin. We have examined the haemostatic properties of PCC using reconstituted whole blood made by mixing coagulation-factor-deficient plasma and washed blood cells.

The influence of inflation rate on the hematologic and hemodynamic effects of intermittent pneumatic calf compression for deep vein thrombosis prophylaxis.

Objective: The study was conducted to determine whether the different inflation rates of intermittent pneumatic compression systems used in deep vein thrombosis prophylaxis influence their hematologic and hemodynamic effects.

Methods: A rapidly inflating intermittent calf compression system and a more gently inflating equivalent were applied to 20 healthy male volunteers for 2 hours each. Venous blood samples were taken for analysis of blood coagulation and fibrinolytic potential.

Reversible inhibition of the platelet procoagulant response through manipulation of the Gardos channel.

The platelet procoagulant response requires a sustained elevation of the intracellular Ca2+ concentration, [Ca2+]i, causing exposure of phosphatidylserine (PS) at the outer surface of the plasma membrane. An increased [Ca2+]i also activates Ca2+-dependent K+ channels. Here, we investigated the contribution of the efflux of K+ ions on the platelet procoagulant response in collagen-thrombin-activated platelets using selective K+ channel blockers.

C-reactive protein-induced in vitro endothelial cell activation is an artefact caused by azide and lipopolysaccharide.

Objective: C-reactive protein (CRP) has been proposed to be an independent risk factor for cardiovascular disease. In vitro studies investigating the mechanism behind this have used purified commercial CRP (cCRP) and endothelial cells. We investigated the role of contaminants in cCRP preparations.

Effects of voluntary exercise on cerebral thrombosis and endothelial function in spontaneously hypertensive rats (SHRSP/Izm).

1. Effects of voluntary exercise on blood pressures, oxidative stress, urinary nitric oxide (NO) level and expression of endothelial NO synthase (eNOS) mRNA were studied in stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2.

A critical role for thrombin in platelet aggregation under high shear stress.

The serine protease, thrombin, plays a crucial role in both coagulation and platelet activation. Anhydrothrombin (AhT) is a catalytically inactive derivative of thrombin in which dehydroalanine replaces the active-site serine. AhT retains affinity for natural substrates of thrombin and may be a competitive inhibitor of thrombin-mediated coagulation and platelet reactions.

Short-term high-dose folic acid does not alter markers of endothelial cell damage in patients with coronary heart disease.

Background And Objective: Endothelial dysfunction is an early, pre-clinical manifestation of coronary heart disease and is associated with increased plasma levels of von Willebrand factor (vWF), soluble E-selectin, and thrombomodulin, markers of endothelial cell damage/activation and reduced nitric oxide bioavailability. Homocysteine is associated with an increased risk of cardiovascular disease and mortality. High-dose folic acid treatment lowers plasma homocysteine by 25% and improves nitric oxide bioavailability; however, the effects on other indices of endothelial cell activation/damage has not been examined in patients with coronary heart disease and normal renal function.

A population based, unselected, consecutive cohort of patients with acquired haemophilia A.

Previous studies in acquired haemophilia A have reported on cohorts of patients referred to specialist centres or were retrospective surveys of specialist centre experience. This may have resulted in the literature representing a more severe group of patients than seen in routine haematological practice. We report on a consecutive, unselected cohort of all patients in south and west Wales who presented with acquired haemophilia A between 1996 and 2002.

A new scoring system to determine thromboembolic risk after heart valve replacement.

Objective: To determine the most important inflammatory and hematologic predictors of thromboembolism (TE) in patients undergoing valve replacement (VR) to be used in conjunction with clinical risk factors for preoperative risk profiling.

Methods And Results: Preoperative and immediately postoperative clinical, echocardiographic, hematologic, biochemical and microbiological parameters were examined prospectively in 370 patients undergoing VR (249 AVR, 93 MVR, 28 DVR). Mean follow-up was 4.

Impaired flow-mediated vasodilation in vivo and reduced shear-induced platelet reactivity in vitro in response to nitric oxide in prothrombotic, stroke-prone spontaneously hypertensive rats.

Previous investigations using an He-Ne laser-induced thrombosis method have shown that stroke-prone spontaneously hypertensive rats (SHRSP) have an enhanced thrombotic tendency in vivo compared to normotensive, Wistar Kyoto rats (WKY). In addition, studies in the presence of acetylcholine have suggested the presence of endothelial dysfunction in SHRSP. In contrast, shear-induced platelet reactivity in vitro appeared to be depressed in SHRSP.

Suppression of argatroban-induced endogenous thrombolysis by PKSI-527, and antibodies to TPA and UPA, evaluated in a rat arterial thrombolysis model.

We have previously confirmed, using a rat mesenteric arteriole thrombolysis model, that thrombin inhibition induces endogenous thrombolysis in vivo. In addition, we have shown that thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the down regulation of endogenous thrombolysis. However, the mechanism of endogenous thrombolysis or spontaneous plasmin generation in vivo remains unclear.

Store-mediated calcium entry in the regulation of phosphatidylserine exposure in blood cells from Scott patients.

Scott syndrome is a bleeding disorder, characterized by impaired surface exposure of procoagulant phosphatidylserine (PS) on platelets and other blood cells, following activation with Ca(2+)-elevating agents. Since store-mediated Ca(2+) entry (SMCE) forms an important part of the Ca(2+) response in various blood cells, it has been proposed that deficiencies in Ca(2+) entry may relate to the impaired PS exposure in the Scott syndrome. Here, we have tested this hypothesis by investigating the relationship between Ca(2+) fluxes and PS exposure in platelets as well as B-lymphoblasts derived from the original Scott patient (M.

Effects of Ginkgo biloba extract (EGb 761) on cerebral thrombosis and blood pressure in stroke-prone spontaneously hypertensive rats.

1. An extract of Ginkgo biloba (EGb 761) has been reported to alleviate cerebrovascular problems. In the present study, we investigated the antithrombotic effects of EGb 761 in cerebral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP/Izm).

Enhanced endogenous thrombolysis induced by a specific factor Xa inhibitor, DX-9065a, evaluated in a rat arterial thrombolysis model in vivo.

We have previously established an animal model to investigate mechanisms of arterial thrombolysis in vivo and have demonstrated that endogenous thrombolysis, mediated by thrombin-activatable fibrinolysis inhibitor, is enhanced by administration of specific thrombin inhibitors. The aim of the present study was to evaluate the effects of a synthetic and specific factor Xa inhibitor, DX-9065a, on endogenous fibrinolysis. Mural thrombi were formed in rat mesenteric arterioles by helium-neon laser irradiation in the presence of Evans blue.