Abstract:
:The heparin-derived oligosaccharide C3 (C3) is currently underdevelopment for the prevention and treatment of vascular dementia and senile dementia of Alzheimer's type. C3 exhibits a molecular weight of 2200-2500 Da with a narrow distribution. The objective of the present study was to assess the pharmacodynamics and pharmacokinetics of C3 in non-human primates. C3 was administered as an intravenous or subcutaneous bolus dose of 1.0 or 2.5 mg/kg. Anti-factor Xa activity, Heptest clotting time and activated partial thromboplastin time were measured to determine pharmacodynamic effects of C3 in plasma. The pharmacokinetics of C3 was primarily characterized by measuring plasma anti-factor Xa activity as a surrogate marker. The rate of absorption and elimination of C3 after administration did not change with increasing dose. The volume of distribution of C3 was small, reflecting a major distribution inside the intravascular space (110-130 ml/kg), and was independent of dose. The total clearance (16.0-21.0 ml/h/kg) and half-life (4-6 h) of C3 were also dose-independent. Within the observed dose range, a 2.5 times of the C3 dose resulted in an area under the plasma concentration-time curve that was approximately 16-27% greater than expected on the basis of linear disposition. These differences could be attributed to the endogenous release of tissue factor pathway inhibitor (TFPI) by C3 at higher doses, which is associated with the vascular effects of C3.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Ma Q,Schultz C,Neville B,Jeske W,Hoppensteadt D,Cornelli U,Lee J,Lorens S,Hanin I,Fareed Jdoi
10.1016/j.thromres.2003.11.008subject
Has Abstractpub_date
2003-01-01 00:00:00pages
249-55issue
4eissn
0049-3848issn
1879-2472pii
S0049384803006169journal_volume
112pub_type
杂志文章abstract:BACKGROUND:Ultrasound has the potential to augment chemical thrombolysis. METHODS AND RESULTS:Thrombotic occlusions in the left circumflex artery (LCx) were induced in 27 dogs. Sixty minutes later, tissue-type plasminogen activator (t-PA) was given intravenously over 90 min. Thrombotic occlusions (n = 20) were treated...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(03)00335-9
更新日期:2003-05-01 00:00:00
abstract::Tissue factor pathway inhibitor is the major potent physiologic inhibitor of tissue factor-induced coagulation. Several potential binding sites for transcription factors have been described in the 750 bp of the 5' flanking region of the human tissue factor pathway inhibitor gene reported earlier. To identify elements ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(99)00040-7
更新日期:1999-09-01 00:00:00
abstract:INTRODUCTION:Nitric oxide (NO) plays an important role in the regulation of the cardiovascular system. It is produced by endothelial nitric oxide synthase (eNOS), which exhibits genetic polymorphisms. Although the clinically relevant polymorphism T(+IhI-786)C reduces eNOS-promoter activity, it is not clear whether circ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2004.09.003
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Pathogenesis of idiopathic pulmonary arterial hypertension (iPAH) includes endothelial dysfunction and in situ thrombosis. A hypercoagulable state has also been postulated but never demonstrated. Our objective was to determine whether patients with iPAH had a hypercoagulable state using calibrated automate...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.08.020
更新日期:2010-12-01 00:00:00
abstract::Four calcium channel blockers (nimodipine, nifedipine, verapamil and diltiazem) of three chemical classes were tested in vitro for inhibition of platelet aggregation using heparinized human platelet rich plasma. Both ADP- and thrombin-induced aggregation were inhibited as was the biosynthesis of thromboxane A2 in resp...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90241-x
更新日期:1984-06-01 00:00:00
abstract::Eicosapentaenoic acid (EPA) has been reported to have a potent anti-aggregatory activity and to be efficiently metabolized by 12-lipoxygenase, not by cyclooxygenase in platelets. In vitro effect of 12-lipoxygenase metabolites of EPA on platelet function was studied and compared with those of arachidonic acid (AA). The...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90248-3
更新日期:1986-02-01 00:00:00
abstract::Murine monoclonal antibodies (mAb) were raised to a purified product of bovine PF-4, a 9,500 dalton protein with heparin neutralization activity comparable to that of human PF-4. Using a non-radioactive slide immunoenzymatic assay, four major classes of mAb could be identified when comparisons were made between purifi...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90384-1
更新日期:1986-03-15 00:00:00
abstract::We evaluate the anti-platelet and anti-thrombotic effects of cilostazol using Multiplate® and PFA-100® in vitro and ex vivo with freshly isolated rat whole blood and in vivo venous and arterial thrombosis models in the same species, in an effort to assess the sensitivity of the whole blood aggregometer assays without ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2011.02.004
更新日期:2011-06-01 00:00:00
abstract::A B S T R A C T Thrombotic events are a major cause of morbidity and mortality in cancer. While the association of venous thromboembolic events with cancer is well documented, in recent years arterial events (i.e. acute myocardial infarction and ischemic strokes) have also emerged as relatively common complications am...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/S0049-3848(20)30398-4
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:Rate of thalidomide-related VTE and risk factors in Japanese myeloma patients are not clear and effects of thromboprophylaxis remain controvertial. PATIENTS AND METHODS:We retrospectively analyzed a cohort data of registered Japanese myeloma patients treated with thalidomide-based regimens between 2009 and ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2012.11.014
更新日期:2013-02-01 00:00:00
abstract:INTRODUCTION:Electronic consultations (eConsults) are asynchronous, consultative electronic-based communications that are aimed to improve efficient and timely access to specialist advice. Our study aim was to evaluate the use and impact of the Canadian Champlain BASE™ (Building Access to Specialists through eConsultat...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.11.002
更新日期:2017-12-01 00:00:00
abstract::Studies of the factors affecting the first recurrence of ischemic stroke have reported inconsistent findings. Types of initial stroke and the racial differences in study samples are among the explanations that may account for this inconsistency. The aims of this study were to estimate the cumulative recurrence rates o...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(99)00146-2
更新日期:2000-02-01 00:00:00
abstract::The cerebral vascular supply is constructed to protect the cerebral hemispheres and brainstem from the consequences of blood flow cessation. Reversal of blood flow around local obstructions is a feature of the microvascular beds of the striatum and cerebral cortex. Cerebral capillaries of these beds consist of endothe...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/s0049-3848(00)00218-8
更新日期:2000-05-01 00:00:00
abstract::Dietary intake of fish oils, rich in the polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has given inconsistent results as to their influence on the plasma fibrinogen level (1, 2, 3, 4, 5, 6). In the present study we have examined the effects of various fatty acids, the ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(95)00152-h
更新日期:1995-10-01 00:00:00
abstract::One of the primary and most serious treatment-related complications in haemophilia A is the formation of anti-factor VIM (FVIII) antibodies, which significantly impacts patient care. For these patients, immunomodulatory therapy becomes important to induce immunological tolerance to FVIII. Immune tolerance induction (I...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(08)70003-3
更新日期:2008-01-01 00:00:00
abstract::Mice were implanted subcutaneously with a pellet containing 0.5 mg estradiol or with a placebo. Eight to 12 days later platelet aggregation was produced in mesenteric arterioles by injuring their endothelium in vivo with a noxious light/dye stimulus. The time between the onset of the noxious stimulus and the appearanc...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90220-8
更新日期:1985-08-01 00:00:00
abstract:INTRODUCTION:Long-term dual antiplatelet therapy (DAPT) has substantially reduced the risk of post-percutaneous coronary intervention (PCI) myocardial infarction and stent thrombosis at the expense of major bleeding. We hypothesized that a short-term DAPT followed by extended P2Y12 inhibitor monotherapy might be approp...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2020.11.038
更新日期:2020-12-07 00:00:00
abstract::The effect of the vasopressin analogue DDAVP on Factor VIII in plasma has been extensively studied in humans. To examine the effect of new and potentially better analogues a suitable animal model has to be established. In the present study trained Beagle dogs were injected with DDAVP and the time course of the Factor ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90363-x
更新日期:1987-09-01 00:00:00
abstract::Prothrombin fragments (F1+2), thrombin-antithrombin complexes (TAT) and D-dimers, markers of hemostatic system activation, were measured in 59 consecutive patients with deep vein thrombosis (DVT). Patients were randomly treated either with subcutaneous unfractionated heparin (UH) administered in two to three subcutane...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0049-3848(02)00023-3
更新日期:2002-02-01 00:00:00
abstract::The variant von Willebrand disease (vWd) variant type 2M (Vicenza) was identified in 13 patients of 7 unrelated families. 11 patients were from different parts of germany and 2 patients from Turkey. Hitherto this variant of vWd has been described only in two families originating from the province of Vicenza in Norther...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(97)00104-7
更新日期:1997-07-01 00:00:00
abstract:INTRODUCTION:Normal pregnancy is associated with hypercoagulable state. Elevated markers of coagulation and fibrinolytic system activation indicate increased thrombin activity and increased fibrinolysis following fibrin formation throughout pregnancy. These changes exceed the biological variability in most cases. Haemo...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.02.005
更新日期:2013-04-01 00:00:00
abstract::Cathepsin A-like enzyme released from human platelets by thrombin hydrolyzed at the highest rate Cbz-Phe-Ala, Cbz-Phe-Met and Cbz-Phe-Leu, did not require activators and was inhibited by DFP, DCI and mercurial compounds (mersalyl acid, PCMS, PCMB and HgCl2). The optimum activity of secreted enzyme was at pH 5.0-6.0. C...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(97)00084-4
更新日期:1997-06-01 00:00:00
abstract::In a prospective clinical trial the risk of infection after application of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III) was investigated in patients undergoing cardiovascular surgery. The study was conducted according to the recommendations of the International Committee on Thrombosi...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/0049-3848(92)90107-l
更新日期:1992-03-15 00:00:00
abstract:BACKGROUND:It has been reported that statin therapy produces additional effects including impaired activation of blood coagulation. It is not clear whether statins can affect hemostasis in patients with acute coronary syndrome. The aim of this study was to investigate the effect of prior statin treatment on thrombin ge...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2009.06.021
更新日期:2010-05-01 00:00:00
abstract::The changes in the fibrinolytic system of rats induced by repeated injections of tissue plasminogen activator (TPA) have been studied. The euglobulin fraction fibrinolytic activity increases 10 min after the first injection of TPA. Repeated injections of TPA for one or more days do not stimulate the fibrinolytic activ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(82)90075-5
更新日期:1982-08-01 00:00:00
abstract:INTRODUCTION:Clinical trials have provided evidence about efficacy and safety of extended thromboprophylaxis among total hip replacement (THR) patients. There is a lack of evidence on effectiveness and safety of extended treatment in unselected patients from routine clinical practice. We examined the effectiveness and ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.11.029
更新日期:2015-02-01 00:00:00
abstract::The effects of ticlopidine treatment (250 mg b.i.d. for 21 months) on fibrinogen and other rheological variables, as compared to placebo, were studied in 44 patients with intermittent claudication due to peripheral arterial occlusive disease. Blood samples were collected every 3 months during this double-blind, random...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0049-3848(88)90134-x
更新日期:1988-12-15 00:00:00
abstract::Evidence is presented for in vitro high affinity binding of serotonin (5-HT) by beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) from human blood. Results include: 1) identification by radioimmunoassay of PF4 in specifically bound material obtained by 5-HT affinity chromatography of human platelet extracts; ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(83)90044-0
更新日期:1983-02-01 00:00:00
abstract:INTRODUCTION:Apoptotic cell death is a highly regulated genetic program, which has been observed in mature megakaryocytes fragmenting into platelets. The clock gene Per2, a key component of core clock oscillator, was involved in affecting both cell cycle control and apoptosis. Thus, loss of Per2 function may be conside...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.11.025
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:Reversal of anticoagulation can be needed in patients undergoing heart valve surgery. ROTEM® has been correlated with international normalized ratio (INR) in patients on warfarin but not with patients on acenocoumarol. This study investigates the reliability of ROTEM® for detecting INR values below the 1.5 t...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/j.thromres.2015.07.003
更新日期:2015-09-01 00:00:00