Bromelain has paradoxical effects on blood coagulability: a study using thromboelastography.

Bromelain is a crude extract from pineapple that is known for a wide array of pharmacological effects including protein digestion, fibrinolytic and anti-immune inflammatory effects and has been popularly used as a phytotherapeutic drug. However, its clinical values and applications remain understudied. The aim of this study was to investigate the effect of bromelain on the coagulability of blood using thromboelastography (TEG).

Comprehensive evaluation of hemostasis in normal women: impact on the diagnosis of mild bleeding disorders.

Women with mild bleeding disorders (MBDs) pose a diagnostic challenge and menorrhagia, the most common presenting symptom that remains underreported. We tested the hypothesis that screening apparently normal females using general and gynecological bleeding assessment tools and a global hemostatic assay together with platelet aggregation can help predict MBDs. We assessed 47 women using electronic bleeding assessment tools; e-bleeding questionnaire; and e-Pictorial Bleeding Assessment Chart (e-PBAC) based on previously validated methods, thrombelastography (TEG), and platelet aggregation together with basic coagulation testing.

Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions.

It is generally accepted that nitric oxide (NO) donors, such as sodium nitroprusside (SNP), or phosphodiesterase 5 (PDE5) inhibitors, including sildenafil, each impact human platelet function. Although a strong correlation exists between the actions of NO donors in platelets and their impact on cGMP, agents such as sildenafil act without increasing global intra-platelet cGMP levels. This study was undertaken to identify how PDE5 inhibitors might act without increasing cGMP.

Adiponectin, ghrelin, and leptin differentially influence human platelet and human vascular endothelial cell functions: implication in obesity-associated cardiovascular diseases.

A very strong epidemiological link exists between obesity, the metabolic syndrome, diabetes and diabetes-associated cardiovascular pathologies. For this reason the peripheral effects of the centrally-acting satiety adipokines, adiponectin and leptin, and of non-adipose-derived hormones with similar effects, like ghrelin, have received considerable attention. In this report, we have extended our previous studies of the pro-thrombotic effects of leptin and determined the effects of adiponectin or ghrelin on human platelet activation.

Von Willebrand factor short sequence repeat locus 2 (intron 40) consists of three polymorphic subloci.

Currently, identification of alleles within the short sequence repeat locus (SSR locus) of intron 40 of the von Willebrand factor gene (previously known as VNTR II) is based on the size of PCR products that only predicts a certain number of repeats. Through cloning and sequencing, we demonstrated the complexity of nucleotide sequence structure of this region by describing three polymorphic tetranucleotide repeat subloci SSR 'a', SSR 'b' and SSR 'c' within the same originally described locus: the original TCTA (9-14 repeats), a small TCTA repeat locus (2 or 3 repeats) located at the 5' end and 30 nucleotides upstream from the original locus and a TGTA repeat locus (5 or 6 repeats), adjacent to the 2/3 repeat locus. Sequencing of 54 VWF alleles has revealed 14 different sequence combinations in this region while the size variability in the region only amounts to a 7-allele system.

Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance.

Thrombocytopenia has been consistently reported following the administration of adenoviral gene transfer vectors. The mechanism underlying this phenomenon is currently unknown. In this study, we have assessed the influence of von Willebrand Factor (VWF) and P-selectin on the clearance of platelets following adenovirus administration.

Leptin-mediated activation of human platelets: involvement of a leptin receptor and phosphodiesterase 3A-containing cellular signaling complex.

An elevated circulating level of the adipocyte-derived satiety hormone leptin is an independent risk factor for cardiovascular disease. Because thrombus formation is a major cause of acute coronary events and leptin was shown previously to facilitate ADP-induced platelet aggregation, we chose to define the signaling events involved in leptin-mediated platelet activation. Using pharmacological, biochemical, and cell biological approaches, we show that leptin-induced platelet activation required activation of a signaling cascade that included the long form of the leptin receptor, three kinases [Janus kinase 2 (JAK2), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (PKB/Akt)], the insulin receptor substrate-1 (IRS-1), and the major human platelet cAMP phosphodiesterase phosphodiesterase 3A (PDE3A).

Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system.

Cyclic AMP (cAMP) and cGMP regulate a myriad of cellular functions, such as metabolism, contractility, motility, and transcription in virtually all cell types, including those of the cardiovascular system. Considerable effort over the last 20 years has allowed identification of the cellular components involved in the synthesis of cyclic nucleotides, as well as effectors of cyclic nucleotide-mediated signaling. More recently, a central role for cyclic nucleotide phosphodiesterase (PDE) has also been elaborated in many cell types, including those involved in regulating the activities of the cardiovascular system.