Adolescent ischemic stroke associated with anabolic steroid and cannabis abuse.

We report on a 16-year-old body builder who suffered from an acute ischemic stroke. In the urine, cannabis metabolites as well as metabolites of the oral androgenic-anabolic steroid methandrostenolone were detected, both known to be associated with stroke events. This report highlights the role of cannabis and steroid abuse that induce strokes in the absence of arteriopathy, cardioembolism or thrombophilia.

Expression and translation of the COX-1b gene in human cells--no evidence of generation of COX-1b protein.

Cyclooxygenase 1b (COX-1b) is a splice variant of COX-1, containing a retained intron 1 within the signal peptide sequence. COX-1b mRNA is found in many species, but the existence of a functionally active protein, which is possibly related to different species-dependent lengths of intron 1, is controversially discussed. The human intron 1 comprises 94 bp, and the resulting frameshift at the intron 1-exon 2 junction creates a premature stop codon.

Crossed cerebellar diaschisis after status epilepticus in a young child.

We report on a 3.8-year-old girl who was born preterm. Due to a posthemorrhagic hydrocephalus she had a ventriculoperitoneal shunt.

Determination of thromboxane formation, soluble CD40L release and thrombopoietin clearance in apheresis platelet concentrates.

All deleterious changes in platelet morphology, structure and function that occur in platelet concentrates (PC) during storage are titled as the 'platelet storage lesion'. No single in vitro test currently available is sufficient in assessing these changes of platelet quality. The release of soluble CD40 Ligand (sCD40L), the formation of thromboxane (TXB2) and the thrombopoietin (TPO) clearance reflect different aspects of platelet metabolism and activitiy, and were used to examine platelet quality in apheresis platelet products.

Thrombin receptors in vascular smooth muscle cells - function and regulation by vasodilatory prostaglandins.

The vast majority of thrombin (>95%) is generated after clotting is completed, suggesting that thrombin formation serves purposes beyond coagulation, such as tissue repair after vessel injury. Two types of vascular thrombin binding sites exist: protease-activated receptors (PARs) and thrombomodulin (TM). Their expression is low in contractile vascular smooth muscle cells (SMC), the dominating subendothelial cell population, but becomes markedly up-regulated upon injury.

8-pCPT-conjugated cyclic AMP analogs exert thromboxane receptor antagonistic properties.

Membrane-permeable 8-(4-chlorophenylthio)-2'-O-methyl cyclic AMP (8-pCPT-2'-O-Me-cAMP) has been shown to specifically activate cAMP-regulated Epac proteins, without direct effects on protein kinase A and protein kinase G. During isometric tension measurements in thoracic aortic rings from Wistar rats, we observed that 8-pCPT-2'-O-Me-cAMP selectively induced a rightward shift of the concentration response curve for the thromboxane mimetic U46619, without altering the contractile response to noradrenaline. We hypothesised that 8-pCPT-2'-O-Me-cAMP and similar compounds may function as direct thromboxane receptor antagonists.

Preliminary evidence for a matrix metalloproteinase-2 (MMP-2)-dependent shedding of soluble CD40 ligand (sCD40L) from activated platelets.

Platelets are the major source of soluble CD40 ligand (sCD40L) in the blood. It has been demonstrated that CD40L is cleaved from the surface of activated platelets to release sCD40L. However, the enzyme involved in sCD40L shedding has not been identified yet.

Delta6-desaturase (FADS2) deficiency unveils the role of omega3- and omega6-polyunsaturated fatty acids.

Mammalian cell viability is dependent on the supply of the essential fatty acids (EFAs) linoleic and alpha-linolenic acid. EFAs are converted into omega3- and omega6-polyunsaturated fatty acids (PUFAs), which are essential constituents of membrane phospholipids and precursors of eicosanoids, anandamide and docosanoids. Whether EFAs, PUFAs and eicosanoids are essential for cell viability has remained elusive.

B cell receptor-induced growth arrest and apoptosis in WEHI-231 immature B lymphoma cells involve cyclic AMP and Epac proteins.

Signaling by the B cell antigen receptor (BCR) is essential for B lymphocyte homeostasis and immune function. In immature B cells, ligation of the BCR promotes growth arrest and apoptosis, and BCR-driven balancing between pro-apoptotic extracellular signal-regulated kinase 1 and 2 (ERK1/2) and anti-apoptotic phosphoinositide 3-kinase-dependent Akt seems to define the final cellular apoptotic response. Dysfunction of these late BCR signaling events can lead to the development of immunological diseases.

Differential effects of factor IIa inhibitors on the endogenous thrombin potential.

Calibrated automated thrombin generation measurement in clotting plasma (endogenous thrombin potential, ETP) is being used increasingly to monitor the effects of anticoagulant drugs. Calibrated automated thrombography measures the concentration of thrombin in clotting plasma by monitoring the cleavage of a fluorogenic substrate (Z-Gly-Gly-Arg-7-amino-4-methylcoumarin) and comparing it with a constant known thrombin activity in a parallel nonclotting sample. This study compared the concentration-dependent effects of different factor IIa inhibitors on the ETP.

Impaired interaction between platelets and endothelial progenitor cells in diabetic patients.

This editorial focuses on new data on the role of platelets of the recruitment of endothelial progenitor cells to sites of vascular lesion and their differentiation into endothelium. Questions of further research are raised.

[Platelet function analysis with point-of-care methods].

Background: More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding.

Methods to evaluate the pharmacology of oral antiplatelet drugs.

Principally, there are two reasons why the pharmacological response to antiplatelet drugs should be measured: on the one hand, an insufficient inhibition of platelet function may result in atherothrombotic complications; on the other hand, an excessive inhibition of platelet function may lead to bleeding complications. The clinical importance to measure the effects of antiplatelet drugs is demonstrated by increasingly growing evidence for an association of resistance to antiplatelet drugs with thromboembolic events. It is often claimed that there is no generally accepted definition of "resistance" and, instead, there is an ongoing semantic discussion about the correct term to be used to describe this phenomenon.

Aspirin "resistance".

Recent clinical studies have shown that the expected antiplatelet effect of aspirin is not always achieved. From the laboratory point of view, resistance to aspirin is the inability to achieve the expected inhibition of platelet cyclooxygenase-(COX-)1 with prevention of platelet thromboxane (TX) A2 formation. The failure to prevent atherothrombotic events (treatment failure) must be distinguished from aspirin resistance.

Complete downmodulation of P-selectin glycoprotein ligand in monocytes undergoing apoptosis.

Objective: Apoptotic monocytes release membrane microparticles which may play a major role in thrombogenicity through a P-selectin glycoprotein ligand (PGSL-1)-mediated mechanism. We have studied systematically the regulation of PSGL-1 expression and function in apoptotic monocytic cells.

Methods And Results: PSGL-1 expression (flow cytometry, immunofluorescence microscopy, immunoblot) was virtually abolished in apoptotic monocytes by proteolytic shedding.

Membrane environment rather than tissue factor expression determines thrombin formation triggered by monocytic cells undergoing apoptosis.

Monocyte apoptosis is an important determinant of atherothrombosis. Two major mechanisms for apoptosis-associated thrombogenicity have been described: exposure of negatively charged membrane phospholipids and up-regulation of tissue factor (TF). However, the relative importance of these mechanisms is unclear.

Alternative splicing of platelet cyclooxygenase-2 mRNA in patients after coronary artery bypass grafting.

Recently, we cloned from platelet mRNA a novel cyclooxygenase (COX)-2 splice variant, designated COX-2a, which is characterized by a partial deletion of exon 5. Preliminary studies of mRNA distribution of COX-2 isoforms in platelets from coronary artery bypass grafting (CABG) patients showed a variable increase in COX-2a mRNA expression after cardiac surgery. Thus, we assessed whether this variant may play a functional role in these patients.

Aspirin-induced platelet inhibition in patients undergoing cardiac surgery.

Platelet function and response to pharmacological inhibition are altered by cardiac surgery. For example, aggregation is increased early after aortic valve replacement (AVR) and platelet response to aspirin is often insufficient after coronary artery bypass grafting (CABG). We hypothesized that the effect of aspirin administration after cardiac surgery might be impaired due to platelet activation.

ICAM-1 and p38 MAPK mediate fibrinogen-induced migration of human vascular smooth muscle cells.

Fibrinogen deposition in the vessel wall represents an independent atherogenic risk factor. In Boyden-chamber assays, fibrinogen concentration-dependently (1-100 microM) induced migration of human vascular smooth muscle cells (SMC). This was inhibited by antibodies to intercellular adhesion molecule-1 (ICAM-1, 10 microg/ml), and by inhibitors of PI3-kinase (LY294002, 10 microM) and MAPK (mitogen-activated protein kinase) p38 (SB203580, 10 microM).

Effects of selective cyclooxygenase isoform inhibition on systemic prostacyclin synthesis and on platelet function at rest and after exercise in healthy volunteers.

To test the hypothesis that selective inhibition of cyclooxygenase (COX)-2 would result in exercise-induced platelet activation by causing a shift in the endogenous thromboxane (TX)/prostacyclin balance, a double blind, randomized study comparing aspirin (300 mg/d) with rofecoxib (25 mg/d) (cross-over design, 14 days washout between treatments) in n = 10 trained healthy volunteers was carried out. Physical exercise resulted only in a minor platelet activation, as reflected by the expression of basal or ADP-stimulated platelet activation markers or basal plasma concentrations of TXB(2). Aspirin significantly reduced TXB(2) in plasma while rofecoxib significantly increased TXB(2) in urine.

Variable platelet response to aspirin in patients with ischemic stroke.

Background: A large number of patients experience ischemic stroke despite treatment with aspirin (acetylsalicylic acid, ASA). It is not clear whether all of these patients with ischemic stroke respond normally to ASA or are hyporesponsive as assessed by inhibition of aggregation and thromboxane (TX) synthesis.

Methods: We studied the effect of ASA given orally and ASA in vitro on collagen- and arachidonic-acid-induced TX formation and aggregation in platelet-rich plasma of 90 patients with ischemic stroke and 25 healthy control subjects.

Cholesterol enhances thrombin-induced release of fibroblast growth factor-2 in human vascular smooth muscle cells.

Objective: The mitogenic response to the G protein-coupled receptor agonist thrombin in human vascular smooth muscle cells (SMCs) depends on release of fibroblast growth factor-2 (FGF-2). Yet, intracellular mechanisms triggering FGF-2 release are unknown. The present study investigates possible effects of cholesterol enrichment and depletion, which have been shown to influence FGF-2-dependent signaling and SMC mitogenesis, on thrombin-induced FGF-2 release.

Alternatively spliced human tissue factor (asHTF) is not pro-coagulant.

It has been proposed that alternatively-spliced human tissue factor (asHTF) is pro-coagulant. We have evaluated the function of asHTF in a mammalian expression system. Full-length human tissue factor (HTF) and asHTF were cloned from smooth muscle cells and over-expressed in HEK293 cells.