Hyperactivity and Pro-inflammatory Functions of Platelets in Diabetes.

Cardiovascular complications claim the lives of up to 70% of patients with diabetes mellitus (DM). The mechanisms increasing cardiovascular risk in DM remain to be fully understood and successfully addressed. Nonetheless, there is increasing evidence in the scientific literature of the participation of platelets in the cardiovascular complications of DM.

Development of New Peptidomimetic NADPH Oxidase Inhibitors with Antithrombotic Properties.

The ability of synthetic peptides inhibitors of NOX1 to effectively block the production of ROS by the enzyme was studied with different methodologies. Specifically, taking advantage of our understanding of the active epitope of the regulatory NOX1 subunit NOXA1 as a potent inhibitor of NOX1-derived O⋅ formation, a panel of peptidomimetic derivatives of this peptide were designed and synthesized with the aim of improving their activity and increasing their stability in plasma. The results highlighted that improved efficacy and potency was found for both the peptide-peptoid hybrid GS2, whereas stapled peptide AC5 and its precursor showed higher stability despite lower biological potency.

Alternative Methods for the Detection of Superoxide Anion Generation in Platelets.

Reactive oxygen species (ROS) are highly unstable oxygen-containing molecules. Their chemical instability makes them extremely reactive and gives them the ability to react with important biological molecules such as proteins, nucleic acids, and lipids. Superoxide anions are important ROS generated by the reduction of molecular oxygen reduction (i.

Patient-tailored platelet transfusion practices for children supported by extracorporeal membrane oxygenation.

Background And Objectives: Extracorporeal membrane oxygenation (ECMO) serves as cardiopulmonary therapy in critically ill patients with respiratory/heart failure and often necessitates multiple blood product transfusions. The administration of platelet transfusions during ECMO is triggered by the presence or risk of significant bleeding. Most paediatric ECMO programmes follow guidelines that recommend a platelet transfusion threshold of 80-100 × 10/L.

Coercion and Compulsory Treatment in Anorexia Nervosa: a Systematic Review on Legal and Ethical Issues.

Background: The aim of this systematic review is to critically summarize current literature concerning ethical and legal issues related compulsory treatment (CT) in patients with anorexia nervosa (AN).

Subjects And Methods: Relevant articles were identified following the PRISMA guidelines after performing title/abstract screening and full text screening. We built the search string using the following terms: "coercion", "compulsory/involuntary treatment", "eating disorders", "anorexia nervosa", "mental capacity", "ethical/legal issues".

Antiplatelet drugs do not protect from platelet-leukocyte aggregation in coronary artery disease.

Background: Despite advances in cardiovascular medicine, coronary artery disease (CAD) remains a leading cause of mortality. Among the pathophysiological features of this condition, platelet-leukocyte aggregates (PLAs) require further attention, either as diagnostic/prognostic disease markers or as potential interventional targets.

Objectives: In this study, we characterized PLAs in patients with CAD.

Human platelets release amyloid peptides β and β in response to haemostatic, immune, and hypoxic stimuli.

Background: Platelets contain high levels of amyloid β (Aβ) peptides and have been suggested to participate in the deposition of amyloid plaques in Alzheimer's Disease (AD).

Objectives: This study aimed to determine whether human platelets release pathogenic Aβ peptides Aβ and Aβ and to characterise the mechanisms regulating this phenomenon.

Methods And Results: Enzyme-linked immunosorbent assays (ELISAs) revealed that the haemostatic stimulus thrombin and the pro-inflammatory molecule lipopolysaccharide (LPS) induce platelet release of both Aβ and Aβ.

The Effect of Medical Clowns on Blood Pressure Measurement in Children Presenting to the Emergency Department.

Background: Blood pressure (BP) is routinely measured while triaging children presenting to the pediatric emergency department (PED).

Objectives: To determine whether a medical clown shortens the time to acquire a BP measurement among children undergoing triage in the PED.

Methods: The study comprised 133 children.

The amyloid peptide β disrupts intercellular junctions and increases endothelial permeability in a NADPH oxidase 1-dependent manner.

Alzheimer's disease is the most common form of dementia and is associated with the accumulation of amyloid peptide β in the brain parenchyma. Vascular damage and microvascular thrombosis contribute to the neuronal degeneration and the loss of brain function typical of this disease. In this study, we utilised a murine model of Alzheimer's disease to evaluate the neurovascular effects of this disease.

A peptide from the staphylococcal protein Efb binds P-selectin and inhibits the interaction of platelets with leukocytes.

Aims: P-selectin is a key surface adhesion molecule for the interaction of platelets with leukocytes. We have shown previously that the N-terminal domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb) binds to P-selectin and interferes with platelet-leukocyte aggregate formation. Here, we aimed to identify the minimal Efb motif required for binding platelets and to characterize its ability to interfering with the formation of platelet-leukocyte aggregates.

Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration.

Cell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known.

Identification of the factor XII contact activation site enables sensitive coagulation diagnostics.

Contact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317-Ser339 that was essential for FXII surface binding and activation, thrombin generation and coagulation.

Diabetes and Thrombosis: A Central Role for Vascular Oxidative Stress.

Diabetes mellitus is the fifth most common cause of death worldwide. Due to its chronic nature, diabetes is a debilitating disease for the patient and a relevant cost for the national health system. Type 2 diabetes mellitus is the most common form of diabetes mellitus (90% of cases) and is characteristically multifactorial, with both genetic and environmental causes.

Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors.

Background: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors.

Objectives: To establish whether PDI and Nox-1 cooperate to control platelet function.

Platelet-derived extracellular vesicles express NADPH oxidase-1 (Nox-1), generate superoxide and modulate platelet function.

Background: Platelets release platelet-derived extracellular vesicles (PDEVs) upon activation - in a process that is regulated by generation of reactive oxygen species (ROS). Platelet NADPH oxidase-1 (Nox-1) contributes to ROS generation and thrombus formation downstream of the collagen receptor GPVI.

Objectives: We aimed to investigate whether PDEVs contain Nox-1 and whether this is relevant for PDEV-induced platelet activation.

NADPH Oxidases Are Required for Full Platelet Activation In Vitro and Thrombosis In Vivo but Dispensable for Plasma Coagulation and Hemostasis.

Objective: Using 3KO (triple NOX [NADPH oxidase] knockout) mice (ie, NOX1/NOX2/NOX4), we aimed to clarify the role of this family of enzymes in the regulation of platelets in vitro and hemostasis in vivo. Approach and Results: 3KO mice displayed significantly reduced platelet superoxide radical generation, which was associated with impaired platelet aggregation, adhesion, and thrombus formation in response to the key agonists collagen and thrombin. A comparison with single-gene knockouts suggested that the phenotype of 3KO platelets is the combination of the effects of the genetic deletion of NOX1 and NOX2, while NOX4 does not show any significant function in platelet regulation.

Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate.

Polyphosphate is a procoagulant inorganic polymer of linear-linked orthophosphate residues. Multiple investigations have established the importance of platelet polyphosphate in blood coagulation; however, the mechanistic details of polyphosphate homeostasis in mammalian species remain largely undefined. In this study, xenotropic and polytropic retrovirus receptor 1 (XPR1) regulated polyphosphate in platelets and was implicated in thrombosis in vivo.

NADPH oxidase 1 is a novel pharmacological target for the development of an antiplatelet drug without bleeding side effects.

Growing evidence supports a central role of NADPH oxidases (NOXs) in the regulation of platelets, which are circulating cells involved in both hemostasis and thrombosis. Here, the use of Nox1 and Nox1 mice as experimental models of human responses demonstrated a critical role of NOX1 in collagen-dependent platelet activation and pathological arterial thrombosis, as tested in vivo by carotid occlusion assays. In contrast, NOX1 does not affect platelet responses to thrombin and normal hemostasis, as assayed in tail bleeding experiments.

Fibrillar amyloid peptides promote platelet aggregation through the coordinated action of ITAM- and ROS-dependent pathways.

Background: Amyloid peptides Aβ40 and Aβ42, whose deposition in brain correlates with Alzheimer disease, are also present in platelets and have prothrombotic activities.

Objective: In this study, we analyze the ability of Aβ peptides to form fibrils and to induce platelet activation and aggregation.

Methods: Aβ40, Aβ42, and their scrambled peptides were diluted in phosphate buffered saline and fibrillogenesis was investigated by ThioflavinT and Congo Red.

Zinc regulates reactive oxygen species generation in platelets.

Vascular complications resulting from atherosclerosis development are a major cause of death. Reactive oxygen species (ROS) are produced by platelets during activation, and have been demonstrated to positively regulate platelet activatory responses. Zn is also an important hemostatic cofactor in platelets, acting both as a platelet agonist and second messenger.