Abstract:
:Hyperglycemia-induced mitochondrial overproduction of reactive oxygen species leads to the activation of different biochemical pathways involved in endothelial damage of the diabetic retina. Tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone] is a dicarbonyl scavenger in the millimolar range and a transition metal ion chelator in the micromolar range. We tested its effect on experimental diabetic retinopathy, and on endothelial cell characteristics in vitro. Streptozotocin diabetic male Wistar rats (60 mg/kg BW) received 50 mg/kg BW tenilsetam (D-T) for 36 weeks, or no treatment (D). The impact of tenilsetam (0-30 mM) on endothelial proliferation, apoptosis, sprouting, cytokine-induced leucocyte-endothelial interaction, and VEGF expression was tested in vitro. Tenilsetam did not affect glycemic control or body weight in diabetic animals. The 3.7 fold increase in acellular capillaries in diabetic rats [p < 0.001 vs. non-diabetic controls (N)] was reduced by 70% (p < 0.001) through treatment, but pericyte loss (D vs. N -33%; p < 0.001) remained unaffected. In vitro, tenilsetam inhibited endothelial proliferation at lower doses, while inducing apoptosis at high doses. Leucocyte adhesion was only inhibited at high doses. Sprouting angiogenesis of bovine retinal endothelial cells was promoted at lower doses (< or = 10 mM). At micromolar concentrations, endothelial VEGF expression was upregulated by 100%. Long-term treatment with the AGE-inhibitor and iron-chelating compound tenilsetam inhibits the formation of acellular capillaries without correcting pericyte loss. The compound has dose-dependent effects on endothelial cell function. These data suggest that, independent of known properties, tenilsetam shows important rescue functions on endothelial cells which could be useful for the treatment of early diabetic retinopathy.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Hoffmann J,Alt A,Lin J,Lochnit G,Schubert U,Schleicher E,Chavakis T,Brownlee M,Van der Woude FJ,Preissner KT,Hammes HPsubject
Has Abstractpub_date
2006-04-01 00:00:00pages
689-95issue
4eissn
0340-6245issn
2567-689Xpii
06040689journal_volume
95pub_type
杂志文章abstract::Hemorrhagic diathesis and widespread microthrombosis are common in heatstroke. To assess the early stages of coagulopathy in heatstroke, thrombin-antithrombin III (TAT), fibrin monomers, plasmin-alpha 2-antiplasmin (PAP), plasminogen and D-Dimer were measured in 16 heatstroke patients (means +/- SE rectal temperature ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::Antithrombin readily undergoes a spontaneous transition from its active five-stranded form to a six-stranded inactive latent form. The recognition of this change in plasma has been obscured by the immediate linkage of newly formed latent antithrombin to a molecule of active antithrombin to give a dimer with an electro...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2001-07-01 00:00:00
abstract::Components of the adaptive immune system, in particular lymphocytes and immunoglobulin, play a major role in advanced atherosclerotic lesions. We sought to determine whether routine, measurements of the relative number of circulating lymphocytes (%L) and gamma-globulin (%G) reflecting immunoglobulin are related to eve...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-07-0449
更新日期:2005-02-01 00:00:00
abstract::Background Polycystic ovarian syndrome (PCOS) affects up to 18% of reproductive-aged women with increased risks of cardiovascular disease and venous thromboembolic disease, related to metabolic and hormonal features, obesity and an apparent hypofibrinolytic state, possibly exacerbated by current PCOS treatments. Objec...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH17-04-0248
更新日期:2017-11-01 00:00:00
abstract::Coumarin and homologous compounds are the most widely used anticoagulant drugs worldwide. They function as antagonists of vitamin K, an essential cofactor for the posttranslational gamma-glutamyl carboxylation of the so-called vitamin K-dependent proteins. As vitamin K hydroquinone is converted to vitamin K epoxide (V...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-02-0082
更新日期:2005-10-01 00:00:00
abstract::Asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and paraoxonase 1 (PON1) are directly involved in the pathogenesis of atherosclerosis by modulation of oxidative stress and/or NO bioavailability. We aimed to assess whether endurance exercise which is known to be cardioprotective could beneficially affect thes...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-03-0158
更新日期:2005-12-01 00:00:00
abstract::Limited data exist on thrombophilia and the risk of venous thrombosis (VT) during pregnancy and postpartum. The objectives of the present study were to investigate the role of haemostatic risk factors for pregnancy-related VT and their phenotypic expression in deep-vein thrombosis (DVT) and pulmonary embolism (PE). To...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-05-0350
更新日期:2012-12-01 00:00:00
abstract::Washed human platelets have been labeled with either 32Pi or glycerol-1-14C and the distribution of the label in the phospholipids determined. 32Pi was introduced primarily into polyphosphoinositides, i.e. di- and triphosphoinositide, whereas the label from glycerol which indicates de novo synthesis of lipid molecules...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1976-04-30 00:00:00
abstract::The acidic mucopolysaccharide extracted from sea cucumber (Stichopus japonicus Selenka) (SJAMP) has been shown to cause platelets to aggregate. Using citrated platelet-rich plasma (PRP), washed platelets and formaldehyde-fixed platelets from humans, we investigated the effects of platelet inhibitors and various plasma...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-06-16 00:00:00
abstract::The effect of thrombin on the phosphorylating activity of platelet membranes was compared to that of trypsin. Preincubation of non-32P phosphorylated platelet membranes with or without either of these two enzymes resulted in a considerable loss of membrane protein kinase activity which was most severe when trypsin was...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1976-06-30 00:00:00
abstract::We examined the effect of a synthetic thrombin inhibitor, MCI-9038, on two experimental animal models of disseminated intravascular coagulation (DIC). In a model that DIC induced by the intravenous infusion of thrombin, MCI-9038 suppressed the decrease of platelet count by about 50% at a dose of 0.2 micrograms/kg/min ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-04-07 00:00:00
abstract::Tissue factor pathway inhibitor (TFPI) is one of the main regulators of the tissue factor (TF) pathway of coagulation. To tether human TFPI to the cell surface, full length or truncated TFPI lacking the third Kunitz domain were fused with domains three and four and the carboxy-terminal sequence of human CD4. Construct...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and is considered as an attractive drug target. We generated two different antibody fragments, an antigen-binding fragment (Fab) and a single-chain variable fragment (scFv), derived from three distinct monoclonal antibodies (MAs) that inhibit t...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH08-09-0834
更新日期:2009-07-01 00:00:00
abstract::Emicizumab, a bispecific monoclonal antibody, bridges activated factor IX (FIXa) and FX, replacing the function of missing FVIIIa to restore effective hemostasis in persons with hemophilia A (PwHA). Here we assess pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers in PwHA with FVIII inhibitors in the Phase III H...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1717114
更新日期:2020-10-21 00:00:00
abstract::Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the ex vivo effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities based on the administration time, and to show how to mask possible inter...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-04-0228
更新日期:2013-01-01 00:00:00
abstract::Stress may counteract responses to antiplatelet drug treatment. We investigated if adding clopidogrel to aspirin treatment could attenutate stress-induced platelet activation and myocardial ischemia in patients with coronary artery disease (CAD). Thirty-one male patients with documented CAD-treated with aspirin (75-16...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:10.1160/th07-05-0323
更新日期:2007-12-01 00:00:00
abstract::Microvascular endothelial damage underlies the pathological changes in haemorrhagic colitis and the haemolytic uraemic syndrome (HUS) caused by enterohaemorrhagic Escherichia coli (EHEC). Shiga toxins (Stxs) are presently the best characterised EHEC virulence factors that can cause the microvascular endothelium injury...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH05-04-0265
更新日期:2005-08-01 00:00:00
abstract::Carboxypeptidase U (CPU, EC 3.4.17.20) is a recently described basic carboxypeptidase which circulates in plasma as the zymogen procarboxypeptidase U (proCPU). In the current study, we report on the presence of the proCPU/CPU system in different mammalian species--pig, guinea pig, dog, mouse, rabbit, rat and human. Th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::Ultra-low-molecular-weight heparins (ULMWHs) with better efficacy and safety ratios are under development; however, there are few structural data available. The main structural features and molecular weight of ULMWHs were studied and compared to enoxaparin. Their monosaccharide composition and average molecular weight...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-11-0795
更新日期:2013-03-01 00:00:00
abstract::The role of platelets in regulating vascular homeostasis has expanded beyond mediation of haemostasis and thrombosis. The discovery of platelet RNA and the presence of subpopulations of platelets containing varying amounts of RNA suggest a role for platelet transcripts in vascular function. As the RNA in anucleated pl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-11-0873
更新日期:2017-05-03 00:00:00
abstract::Heparin-coating improves the biocompatibility of blood contacting artificial surfaces. This led us to investigate the impact of heparin-coating (Carmeda AB, Stockholm) of polymetylmetacrylate on the expression of monocyte tissue factor procoagulant activity (TF-PCA) by surface adhesion. Also, the anticoagulant effect ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Acute myocardial infarction (AMI) is associated with activation of various cells, including platelets that form monocyte-platelet complexes (MPCs). Here, we analysed MPC in vivo and in vitro and investigated the abilities of different monocyte subclasses to form MPC, the characteristics of the cells involved in MPC fo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1673342
更新日期:2018-11-01 00:00:00
abstract::The mechanism of thrombin induction of tissue- and urokinase-type plasminogen activator (t-PA and u-PA) biosynthesis was investigated in cultured human fetal lung fibroblast cells, IMR-90. Northern blot analysis of total RNA from thrombin-treated cells showed marked accumulations of both t-PA and u-PA mRNA during 24 h...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::We measured and compared the levels of plasma soluble (s) P-selectin, sCD40L, platelet-derived microparticles (PDMP), monocyte-derived microparticles (MDMP), and anti-oxidized LDL antibody, to obtain a better understanding of their potential contribution to vascular complications in acute coronary syndrome (ACS). The ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-04-0247
更新日期:2004-01-01 00:00:00
abstract::An experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue fact...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Angiogenic activity and formation of a vascular network facilitate tumor perfusion and play a critical role in tumor growth and metastasis. Tumor vasculature may be visualized by means of parametric imaging of specific morphological and physiological characteristics that collectively describe its properties. In this r...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2003-01-01 00:00:00
abstract::In the present research protein analysis on SDS-polyacrylamide gel electrophoresis (PAGE) has been used to study the glycoprotein pattern of the blood platelets of four members from a family affected by May-Hegglin anomaly. In order to characterize the glycoprotein fractions, lactoperoxidase-iodination and immunopreci...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-12-17 00:00:00
abstract::Tissue thromboplastin apoprotein was partially purified from human brain. The apoprotein was recombined with mixed phospholipids to yield active thromboplastin. The recombined thromboplastin induced proteolytic activation of isolated human factor IX in the presence of factor VII and Ca2+. The clotting times of various...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-08-24 00:00:00
abstract::The core protein components of the plasminogen activator (PA) system are two plasminogen activators, two plasminogen activator inhibitors and a urokinase type plasminogen activator-specific cell surface receptor. Various types of biological regulation are exerted through the interplay of these components mutually and ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH04-12-0814
更新日期:2005-04-01 00:00:00
abstract::In conclusion, we believe that the baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, the effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require test...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1987-10-28 00:00:00