Coordinated responses of natural anticoagulants to allogeneic stem cell transplantation and acute GVHD - A longitudinal study.

Background: Allogeneic stem cell transplantation (SCT) enhances coagulation via endothelial perturbation and inflammation. Role of natural anticoagulants in interactions between coagulation and inflammation as well as in acute graft-versus-host disease (GVHD) are not well known. The purpose of this study was to define changes in natural anticoagulants over time in association with GVHD.

Initial results of inflammatory response, matrix remodeling, and reactive oxygen species following PCI in acute ischemic myocardial injury in man.

Background: Neutrophils and reactive oxygen species (ROS) are suggested to be involved in irreversible myocardial reperfusion injury and stunning. We investigated the relations between circulating biochemical markers and myocardium at risk (MaR), myocardial infarct (MI) size, salvage, and recovery of function in man.

Methods And Results: In patients undergoing PCI serial blood samples were acquired for markers of inflammatory response (myeloperoxidase [MPO], neutrophil-gelatinase-associated lipocalin [NGAL], interleukins 6 and 8 [IL-6/8], tumor necrosis factor-a [TNF-a], high-sensitive C-reactive protein [hsCRP]), matrix remodeling (matrixmetalloproteinase-9 [MMP-9]) and ROS (malondialdehyde [MDA], isoprostane [IsoP]).

Thrombomodulin as a marker for bleeding complications during warfarin treatment.

Background: The major adverse effect of warfarin treatment is hemorrhage. Several risk factors for bleeding complications are also risk factors for thromboembolic events, making the clinical decision to initiate or withhold anticoagulant treatment difficult. Specific markers that solely identify patients at high risk of bleeding would have great clinical impact.

Low plasma activated protein C-protein C inhibitor complex concentration is associated with vascular access failure in hemodialysis patients.

Background: Vascular access failure is a common cause of morbidity in patients with end-stage renal failure on hemodialysis (HD). Activation of the coagulation system and formation of a thrombus play important roles in recurrent arteriovenous fistula/graft (AVFG) failure. Thrombin in complex with thrombomodulin (TM) activates the anticoagulant protein C and creates activated protein C (APC), which is subsequently inactivated by the protein C inhibitor (PCI).

Dissociation of the Inflammatory Reaction following PCI for Acute Myocardial Infarction.

Objectives: Neutrophils are activated and infiltrate the myocardium after ischemia and reperfusion. The involvement of neutrophils in irreversible reperfusion injury is suggested by numerous experimental studies. The aim of this study was to investigate markers of neutrophil activation following reperfusion of acute myocardial infarction (AMI) accomplished with percutaneous coronary intervention (PCI) and their relationship to markers of lipid peroxidation, cytokines and highly-sensitive C-reactive protein (hsCRP).

Venous thromboembolism in carriers of the Factor V Leiden mutation and in patients without known thrombophilic risk factor; prediction of recurrence and APC-PCI complex concentration and/or soluble thrombomodulin antigen and activity.

Background: The complex between activated protein C (APC) and the protein C inhibitor (PCI) is a sensitive indicator of the degree of activation of blood coagulation and higher concentrations have been measured in carriers of the FV Leiden mutation who were in the recovery phase after treatment for venous thromboembolism (VTE).

Objectives: The main purpose of this study was to correlate the APC-PCI complex concentration to thrombomodulin activity and antigen concentration in the same group of patients. We also add a prospective clinical follow-up of the VTE recurrence after 1 year to investigate if the markers can predict the risk for a new VTE.

Lipid peroxidation is not increased in heart failure patients on modern pharmacological therapy.

Background: Previous studies support a role of oxygen-free radicals in the development of congestive heart failure (CHF). The aim of this study was to investigate whether lipid peroxidation is increased in CHF patients on modern pharmacological therapy and whether there is a positive correlation between plasma levels of markers of lipid peroxidation and severity of heart failure (HF). Plasma malondialdehyde (MDA) and isoprostanes are often used as markers of lipid peroxidation and oxidative stress.

Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease--a prospective randomized study of vitamin supplementation.

Background: Elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of developing occlusive vascular diseases. To better illustrate the relationship between plasma tHcy concentration, oxidative stress, and inflammation in patients with coronary artery disease (CAD), we measured plasma 8-isoprostane-prostaglandin F 2 (Iso-P), plasma malondialdehyde (MDA), and several markers of inflammation. We also aimed to demonstrate the effects of vitamin supplementation on these markers.

Genetic variation in the human thrombomodulin promoter locus and prognosis after acute coronary syndrome.

Introduction: Endothelial thrombomodulin (TM) plays a critical role in both anticoagulation and anti-inflammation. An impaired TM cofactor function or reduced TM gene expression could constitute a prethrombotic abnormality leading to acute coronary events. Mutations in the TM gene occur, but their functional consequences on the expression and activity of the gene are not yet fully understood.

No increase of plasma malondialdehyde after primary coronary angioplasty for acute myocardial infarction.

Objective: Free radicals formed after coronary artery occlusion and reperfusion are assumed to produce myocardial stunning and possibly other forms of reperfusion injury as well. Malondialdehyde (MDA) is an end product in the lipid peroxidation chain reaction and is frequently used as a marker for free oxygen radical production. Increased levels of plasma MDA have been found following successful thrombolytic therapy.

Naturally occurring mutations in the thrombomodulin gene leading to impaired expression and function.

Sporadic mutations in the thrombomodulin (TM) gene occur in patients with both arterial and venous thrombosis, but the effects of these mutations on expression and function are largely unexplored. Full-length wild-type TM complementary DNA (cDNA) was incorporated into vector pcDNA6 for transfection into COS-7 cells for transient expression. Mutagenesis was performed to create 7 TM mutants with natural mutations either previously identified (Ala25Thr, Gly61Ala, Asp468Tyr, Pro477Ser, Pro483Leu) or reported here (an 11-base pair [bp] deletion, del791-801, leading to STOP306, and a missense mutation, Arg385Ser).