Platelet Transport Research Articles

Optimization design of semi-open impeller based on thrombogenicity in a blood pump.

Blood clots are composed of aggregated fibrin and platelets, and thrombosis is the body's natural response to repairing injured blood vessels or stopping bleeding. However, when this process is activated abnormally, such as in a mechanical blood pump, it can lead to excessive thrombus formation. Therefore, how to avoid or reduce the probability of thrombus formation is an important indicator of the stable operation of a blood pump. In this paper, Lagrangian particle tracking trajectories are simulated to study platelet transport in a blood pump. The design of the thrombus blood pump was optimized using an orthogonal design method based on three factors: inlet angle, outlet angle, and blade number. The effect of blood pump pressure, rotational speed, impeller outlet angle, inlet angle, and number of blades on thrombus formation was analysed using Fluent software. The thrombogenic potential was derived by analyzing the trajectory and flow parameters of platelet particles in the blood pump, as well as the statistical parameters of residence time and stress accumulation thrombus in the platelet pump. When the impeller inlet angle is 30°, the outlet angle is 20°, and the number of blades is 6, the probability of thrombus formation is minimized in the orthogonal design method, aligning with the requirements for blood pump performance. These design parameters serve as a numerical guideline for optimizing the geometry of the semi-open impeller in blood pumps and provide a theoretical foundation for subsequent invitro experiments.

Membrane Transporter of Serotonin and Hypercholesterolemia in Children.

The serotonin membrane transporter is one of the main mechanisms of plasma serotonin concentration regulation. Serotonin plays an important role in the pathogenesis of various cardiovascular diseases, stimulating the proliferation of smooth muscle cells, key cells in the process of hypertrophic vascular remodeling. Vascular remodeling is one of the leading prognostically unfavorable factors of atherosclerosis, the main manifestation of familial hypercholesterolemia. Familial hypercholesterolemia is one of the most common genetically determined lipid metabolism disorders and occurs in 1 in 313 people. The aim of our study was to investigate the levels of plasma and platelet serotonin, 5-hydroxyindoleacetic acid, and membrane transporter in a cross-sectional study of two pediatric groups, including patients with familial hypercholesterolemia and the control group, which consisted of apparently healthy children without cardiovascular diseases. The study involved 116 children aged 5 to 17 years old. The proportion of boys was 50% (58/116) and the average age of the children was 10.5 years (CI 2.8-18.1). The concentrations of serotonin in blood plasma and platelets and 5-hydroxyindoleacetic acid were higher in children with familial hypercholesterolemia than in the controls. The concentration of the serotonin transporter in platelets in healthy children, compared with the main group, was 1.3 times higher. A positive correlation was revealed between the level of serotonin (5-HT and PWV: ρ = 0.6, p < 0.001), its transporter (SERT and PWV: ρ = 0.5, p < 0.001), and the main indicators of arterial vascular stiffness. Our study revealed the relationship between high serotonin and SERT concentrations and markers of arterial stiffness. The results we obtained suggest the involvement of serotonin and SERT in the process of vascular remodeling in familial hypercholesterolemia in children.

RhoGAP6 interacts with COPI to regulate protein transport.

RhoGAP6 is the most highly expressed GTPase-activating protein (GAP) in platelets specific for RhoA. Structurally RhoGAP6 contains a central catalytic GAP domain surrounded by large, disordered N- and C-termini of unknown function. Sequence analysis revealed three conserved consecutive overlapping di-tryptophan motifs close to the RhoGAP6 C-terminus which were predicted to bind to the mu homology domain (MHD) of δ-COP, a component of the COPI vesicle complex. We confirmed an endogenous interaction between RhoGAP6 and δ-COP in human platelets using GST-CD2AP which binds an N-terminal RhoGAP6 SH3 binding motif. Next, we confirmed that the MHD of δ-COP and the di-tryptophan motifs of RhoGAP6 mediate the interaction between both proteins. Each of the three di-tryptophan motifs appeared necessary for stable δ-COP binding. Proteomic analysis of other potential RhoGAP6 di-tryptophan motif binding partners indicated that the RhoGAP6/δ-COP interaction connects RhoGAP6 to the whole COPI complex. 14-3-3 was also established as a RhoGAP6 binding partner and its binding site was mapped to serine 37. We provide evidence of potential cross-regulation between 14-3-3 and δ-COP binding, however, neither δ-COP nor 14-3-3 binding to RhoGAP6 impacted RhoA activity. Instead, analysis of protein transport through the secretory pathway demonstrated that RhoGAP6/δ-COP binding increased protein transport to the plasma membrane, as did a catalytically inactive mutant of RhoGAP6. Overall, we have identified a novel interaction between RhoGAP6 and δ-COP which is mediated by conserved C-terminal di-tryptophan motifs, and which might control protein transport in platelets.

Initial platelet aggregation in the complex shear environment of a punctured vessel model

To analyze flow conditions and cellular behavior at the onset of a hemostatic response in the injury of a microneedle-induced vessel puncture, a combined in silico and in vitro platform is created. A cell-resolved blood flow model is utilized for in-depth flow profile and cell distribution analyses, and a novel punctured vessel flow chamber is set up to complement the simulations with the evaluation of platelet aggregation around the wound neck of the puncture. The respective setups of the platform are explained, and the results of both experiments and simulations with various puncture diameters and pressure drops are combined, providing detailed insight into the basic processes of platelet transport and aggregation in the wound area. A special emphasis of the simulation evaluation is put on the cell distributions and the magnitude of shear rate and elongational flow in the wound neck area, as well as downstream from the puncture. Additionally, possible implications of wound size and pressure difference on the hemostatic response are discussed. The simulations display asymmetric cell distributions between the proximal and distal sides of the wound neck in regard to the flow direction. The flow chamber with the puncture diameter closest to the simulated domains confirms this asymmetry by displaying increased platelet aggregation at the wound neck's distal side. The presented punctured vessel in silico and in vitro experimental setups offer a platform to analyze the hemostatic environment of a vessel injured by a puncture and might assist in identifying differentiating factors between primary hemostasis and arterial thrombosis.

Red blood cells contribution in blood coagulation

For a long time, red blood cells have been known to have a procoagulant effect on hemostatic system. This effect was usually ascribed to either general increase of blood viscosity due to increased hematocrit value, RBCs' transport-enhancing effect on platelets adhesion under flow conditions. It is known that red blood cells can have a procoagulant effect on the hemostasis system. This effect is usually explained either by a general increase in blood viscosity due to an increase in hematocrit, or by the effect of red blood cells on the transport of platelets to the vessel wall and their further adhesion. However, recent studies indicate that the role of red blood cells in blood coagulation is much wider. In this review, we will consider the main mechanisms currently known, through which red blood cells can influence the processes of hemostasis and thrombosis in normal and pathological conditions.

Shear induced diffusion of platelets revisited.

The transport of platelets in blood is commonly assumed to obey an advection-diffusion equation with a diffusion constant given by the so-called Zydney-Colton theory. Here we reconsider this hypothesis based on experimental observations and numerical simulations including a fully resolved suspension of red blood cells and platelets subject to a shear. We observe that the transport of platelets perpendicular to the flow can be characterized by a non-trivial distribution of velocities with and exponential decreasing bulk, followed by a power law tail. We conclude that such distribution of velocities leads to diffusion of platelets about two orders of magnitude higher than predicted by Zydney-Colton theory. We tested this distribution with a minimal stochastic model of platelets deposition to cover space and time scales similar to our experimental results, and confirm that the exponential-powerlaw distribution of velocities results in a coefficient of diffusion significantly larger than predicted by the Zydney-Colton theory.

The effect of stiffened diabetic red blood cells on wall shear stress in a reconstructed 3D microaneurysm

Blood flow within the vasculature of the retina has been found to influence the progression of diabetic retinopathy. In this research cell resolved blood flow simulations are used to study the pulsatile flow of whole blood through a segmented retinal microaneurysm. Images were collected using adaptive optics optical coherence tomography of the retina of a patient with diabetic retinopathy, and a sidewall (sacciform) microaneurysm was segmented from the volumetric data. The original microaneurysm neck width was varied to produce two additional aneurysm geometries in order to probe the influence of neck width on the transport of red blood cells and platelets into the aneurysm. Red blood cell membrane stiffness was also increased to resolve the impact of rigid red blood cells, as a result of diabetes, in blood flow. Wall shear stress and wall shear stress gradients were calculated throughout the aneurysm domains, and the quantification of the influence of the red blood cells is presented. Average wall shear stress and wall shear stress gradients increased due to the increase of red blood cell membrane stiffness. Stiffened red blood cells were also found to induce higher local wall shear stress and wall shear stress gradients as they passed through the leading and draining parental vessels. Stiffened red blood cells were found to penetrate the aneurysm sac more than healthy red blood cells, as well as decreasing the margination of platelets to the vessel walls of the parental vessel, which caused a decrease in platelet penetration into the aneurysm sac.

Continuum modeling of thrombus formation and growth under different shear rates

Obstruction of blood flow due to thrombosis is a major cause of ischemic stroke, myocardial infarction, and in severe cases, mortality. In particular, in blood wetting medical devices, thrombosis is a common reason for failure. The prediction of thrombosis by understanding signaling pathways using computational models, lead to identify the risk of thrombus formation in blood-contacting devices and design improvements. In this study, a mathematical model of thrombus formation and growth is presented. A biochemical model of platelet activation and aggregation is developed to predict thrombus size and shape at the site of vascular injury. Computational fluid dynamics using the finite volume method is employed to compute the velocity and pressure fields which are influenced by the growing thrombi. The passive transport of platelets, agonists, the platelet activation kinetics, their adhesion to the growing thrombi and embolization of platelets are solved by a fully coupled set of convection–diffusion–reaction equations. The thrombogenic surface representing blood-contacting material or injured blood vessel was incorporated into the model as a surface flux boundary condition to initiate thrombus formation. The blood is considered as a Newtonian fluid, while the thrombus is treated as a porous medium. The results are compared with in vitro experiments of a microfluidic chamber at an initial inlet venous shear rate of 200s−1 using a pressure–inlet boundary condition. The thrombus development due to agonist concentrations and change in the shear rate as well as thromboembolism for this benchmark problem is successfully computed. Furthermore, to extend the current model to a physiologically relevant configuration, thrombus formation in a blood tube is simulated. Two different heterogeneous reaction rates for platelet aggregation are used to simulate thrombus growth under a constant inlet flow rate. The findings show that the thrombus shape can be substantially altered by the hemodynamic conditions, increase in the shear rate and due to the combined effects of shear induced platelet activation and the heterogeneous reaction rates. It is also concluded that the model is able to predict thrombus formation in different physiological and pathological hemodynamics.

Multiphase continuum modeling of thrombosis in aneurysms and recirculation zones

Aneurysms of saccular shape are usually associated with a slow, almost stagnant blood flow, as well as a consequent emergence of blood clots. Despite the practical importance, there is a lack of computational models that could combine platelet aggregation, precise biorheology, and blood plasma coagulation into one efficient framework. In the present study, we address both the physical and biochemical effects during thrombosis in aneurysms and blood recirculation zones. We use continuum description of the system and partial differential equation-based model that account for fluid dynamics, platelet transport, adhesion and aggregation, and biochemical cascades of plasma coagulation. The study is focused on the role of transport and accumulation of blood cells, including contact interactions between platelets and red blood cells (RBCs), coagulation cascade triggered by activated platelets, and the hematocrit-dependent blood rheology. We validated the model against known experimental benchmarks for in vitro thrombosis. The numerical simulations indicate an important role of RBCs in spatial propagation and temporal dynamics of the aneurysmal thrombus growth. The local hematocrit determines the viscosity of the RBC-rich regions. As a result, a high hematocrit slows down flow circulation and increases the presence of RBCs in the aneurysm. The intensity of the flow in the blood vessel associated with the aneurysm also affects platelet distribution in the system, as well as the steady shape of the thrombus.

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. We used bioinformatic analyses of omics data to identify XPR1 as a major phosphate transporter in platelets. XPR1 messenger RNA and protein expression inversely correlated with intracellular polyphosphate content and release. Pharmacological interference with XPR1 activity increased polyphosphate stores, led to enhanced platelet-driven coagulation, and amplified thrombus formation under flow via the polyphosphate/factor XII pathway. Conditional gene deletion of Xpr1 in platelets resulted in polyphosphate accumulation, accelerated arterial thrombosis, and augmented activated platelet-driven pulmonary embolism without increasing bleeding in mice. These data identify platelet XPR1 as an integral regulator of platelet polyphosphate metabolism and reveal a fundamental role for phosphate homeostasis in thrombosis.

Multicenter observational study evaluating the impact of platelet transport bags on product wastage.

Platelets are the most commonly discarded blood product in Canada, with the most common cause of in-date product loss being improper storage. Transport containers to maintain temperature and extend acceptable return time may represent a method to reduce wastage. The objective of this study was to evaluate the impact of a validated Platelet Transport Bag (PTB) on platelet wastage. Thirty-six hospitals with the highest platelet discards were invited to participate in a before-after observational study. Hospitals were instructed to utilize a validated 4-h PTB for clinical situations where immediate transfusion was not planned. Five hospitals audited in-date platelet discards from July 2018 to November 2019 to characterize wastage causes. In-date platelet discard data 12 months before and after the start date for each site were analyzed to determine changes in wastage. Of 36 hospital sites, 16 agreed to participate. Pre- and postdiscards were 277 and 301, respectively, for all sites combined. There were no significant before-after change in wastage rate (+0.05%, p = .51). Fifty discards were included in the detailed audit; the most common reasons were return to the blood bank after more than 60 min outside a PTB (n = 17, 34%) and return in a red cell cooler (n = 10, 20%). Implementation of PTB did not improve wastage. Common causes of in-date discards were return after 1 h outside of a PTB and placement in a red cell cooler in error. Further research is required to investigate potential strategies to mitigate in-date platelet wastage.

Digital blood in massively parallel CPU/GPU systems for the study of platelet transport.

We propose a highly versatile computational framework for the simulation of cellular blood flow focusing on extreme performance without compromising accuracy or complexity. The tool couples the lattice Boltzmann solver Palabos for the simulation of blood plasma, a novel finite-element method (FEM) solver for the resolution of deformable blood cells, and an immersed boundary method for the coupling of the two phases. The design of the tool supports hybrid CPU–GPU executions (fluid, fluid–solid interaction on CPUs, deformable bodies on GPUs), and is non-intrusive, as each of the three components can be replaced in a modular way. The FEM-based kernel for solid dynamics outperforms other FEM solvers and its performance is comparable to state-of-the-art mass–spring systems. We perform an exhaustive performance analysis on Piz Daint at the Swiss National Supercomputing Centre and provide case studies focused on platelet transport, implicitly validating the accuracy of our tool. The tests show that this versatile framework combines unprecedented accuracy with massive performance, rendering it suitable for upcoming exascale architectures.

Spherization of red blood cells and platelet margination in COPD patients.

Red blood cells (RBCs) in pathological situations undergo biochemical and conformational changes, leading to alterations in rheology involved in cardiovascular events. The shape of RBCs in volunteers and stable and exacerbated chronic obstructive pulmonary disease (COPD) patients was analyzed. The effects of RBC spherization on platelet transport (displacement in the flow field caused by their interaction with RBCs) were studied in vitro and by numerical simulations. RBC spherization was observed in COPD patients compared with volunteers. In in vitro experiments at a shear rate of 100 s-1 , treatment of RBCs with neuraminidase induced greater sphericity, which mainly affected platelet aggregates without changing aggregate size. At 400 s-1 , neuraminidase treatment changes both the size of the aggregates and the number of platelet aggregates. Numerical simulations indicated that RBC spherization induces an increase of the platelet mean square displacement, which is traditionally linked to the platelet diffusion coefficient. RBCs of COPD patients are more spherical than healthy volunteers. Experimentally, RBC spherization induces increased platelet transport to the wall. Additional studies are needed to understand the link between the effect of RBCs on platelet transport and the increased cardiovascular events observed in COPD patients.

Membrane serotonin transporter as a Biomarker of Pulmonary arterial hypertension in children with Congenital Heart Defect

18 young children (aged from 1 month old to 2 years old) with congenital heart disease were observed. During observation they were divided into 2 groups. Group I-8 children with CHD, not complicated by PAH. Group II 11 children with CHD, complicated by PAH. The content of serotonin and its transporter in platelets, the amount of serotonin in serum were determined. Serotonin content was determined by enzyme-linked immunosorbent assay. The study was performed using the Serotonin ELISA diagnostic kit, IBL Hamburg on the Evolis automated robotic station (BioRad). To determine the Sodium-Dependent serotonin transporter (SLC6A4) there was used the method of quantitative sandwich ELISA of Cusabio production. The main initiator of the development of PAH is development of endothelial dysfunction of the pulmonary vessels. Since the cause of this dysfunction is associated with functional disorders of the serotonergic system, our task was to determine the content of SERT and serotonin in platelets in the studied groups. We suggest that the serotonin transporter (SERT), which is responsible for the proliferation of the pulmonary artery smooth-muscle cells (PASMC), can be used as a biomarker for predicting and diagnosing PAH in children with CHD. The need for early biomarkers in the diagnosis of PAH in children is claimed by scientists from many countries of the world [1, 2]. The results of our studies showed a significant increase in the concentration of SERT in platelets in group II, compared with group I more than several times. The serotonin content in platelets in children of group II tended to decrease as compared with group I. Perhaps, an excessive increase in transporters in platelets is sufficient in itself for the induction of PASMC hyperplasia and the subsequent development of PAH. It is necessary to continue research in this direction, which will help to reveal and understand the molecular mechanisms by which SERT regulates the proliferation of PASMC and the role of serotonin and its transporter in the development of PAH in children.

Identifying the start of a platelet aggregate by the shear rate and the cell-depleted layer.

Computer simulations were performed to study the transport of red blood cells and platelets in high shear flows, mimicking earlier published in vitro experiments in microfluidic devices with high affinity for platelet aggregate formation. The goal is to understand and predict where thrombus formation starts. Additionally, the need of cell-based modelling in these microfluidic devices is demonstrated by comparing our results with macroscopic models, wherein blood is modelled as a continuous fluid. Hemocell, a cell-based blood flow simulation framework is used to investigate the transport physics in the microfluidic devices. The simulations show an enlarged cell-depleted layer at the site where a platelet aggregate forms in the experiments. In this enlarged cell-depleted layer, the probability to find a platelet is higher than in the rest of the microfluidic device. In addition, the shear rates are sufficiently high to allow for the von Willebrand factor to elongate in this region. We hypothesize that the enlarged cell-depleted layer combined with a sufficiently large platelet flux and sufficiently high shear rates result in an haemodynamic environment that is a preferred location for initial platelet aggregation.

Cell-resolved blood flow simulations of saccular aneurysms: effects of pulsatility and aspect ratio.

We study the effect of pulsatile flow on the transport of red blood cells (RBCs) and platelets into aneurysm geometries with varying dome-to-neck aspect ratios (AR). We use a validated two-dimensional lattice Boltzmann model for blood plasma with a discrete element method for both RBCs and platelets coupled by the immersed boundary method. Flow velocities and vessel diameters were matched with measurements of cerebral perforating arteries and flow was driven by a synthetic heartbeat curve typical for such vessel sizes. We observe a flow regime change as the aspect ratio increases from a momentum-driven regime in the small aspect ratio to a shear-driven regime in the larger aspect ratios. In the small aspect ratio case, we see the development of a re-circulation zone that exhibits a layering of high (greater than or equal to 7 s) and low (less than 7 s) residence cells. In the shear-driven regime, we see high and low residence cells well mixed, with an increasing population of cells that are trapped inside the aneurysm as the aspect ratio increases. In all cases, we observe aneurysms that are platelet-rich and red blood cell-poor when compared with their respective parental vessel populations. Pulsatility also plays a role in the small aspect ratio as we observe a smaller population of older trapped cells along the aneurysm wall in the pulsatile case when compared with a steady flow case. Pulsatility does not have a significant effect in shear-driven regime aspect ratios.

Quantifying Platelet Margination in Diabetic Blood Flow

Patients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities strongly associated with cardiovascular diseases. In addition to the changes of numerous coagulation factors such as elevated levels of thrombin and fibrinogen, the abnormal rheological effects of red blood cells (RBCs) and platelets flowing in blood are crucial in platelet adhesion and thrombus formation in T2DM. An important process contributing to the latter is the platelet margination. We employ the dissipative particle dynamics method to seamlessly model cells, plasma, and vessel walls. We perform a systematic study on RBC and platelet transport in cylindrical vessels by considering different cell shapes, sizes, and RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and hematocrit. In particular, we use cellular-level RBC and platelet models with parameters derived from patient-specific data and present a sensitivity study. We find T2DM RBCs, which are less deformable compared to normal RBCs, lower the transport of platelets toward the vessel walls, whereas platelets with higher mean volume (often observed in T2DM) lead to enhanced margination. Furthermore, increasing the flowrate or hematocrit enhances platelet margination. We also investigated the effect of platelet shape and observed a nonmonotonic variation with the highest near-wall concentration corresponding to platelets with a moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs), whose count is increased notably in T2DM patients. We find that WBC rolling or WBC adhesion tends to decrease platelet margination due to hydrodynamic effects. To the best of our knowledge, such simulations of blood including all blood cells have not been performed before, and our quantitative findings can help separate the effects of hydrodynamic interactions from adhesive interactions and potentially shed light on the associated pathological processes in T2DM such as increased inflammatory response, platelet activation and adhesion, and ultimately thrombus formation.

Impact of strut dimensions and vessel caliber on thrombosis risk of bioresorbable scaffolds using hemodynamic metrics.

Bioresorbable scaffolds (BRS) promise to be the treatment of choice for stenosed coronary vessels. But higher thrombosis risk found in current clinical studies limits the expectations. Three hemodynamic metrics are introduced to evaluate the thrombosis risk of coronary stents/scaffolds using transient computational fluid dynamics (CFD). The principal phenomena are platelet activation and effective diffusion (platelet shear number, PSN), convective platelet transport (platelet convection number, PCN) and platelet aggregation (platelet aggregation number, PAN) were taken into consideration. In the present study, two different stent designs (thick-strut vs. thin-strut design) positioned in small- and medium-sized vessels (reference vessel diameter, RVD=2.25 mm vs. 2.70 mm) were analyzed. In both vessel models, the thick-strut design induced higher PSN, PCN and PAN values than the thin-strut design (thick-strut vs. thin-strut: PSN=2.92/2.19 and 0.54/0.30; PCN=3.14/1.15 and 2.08/0.43; PAN: 14.76/8.19 and 20.03/10.18 for RVD=2.25 mm and 2.70 mm). PSN and PCN are increased by the reduction of the vessel size (PSN: RVD=2.25 mm vs. 2.70 mm=5.41 and 7.30; PCN: RVD=2.25 mm vs. 2.70 mm=1.51 and 2.67 for thick-strut and thin-strut designs). The results suggest that bulky stents implanted in small caliber vessels may substantially increase the thrombosis risk. Moreover, sensitivity analyses imply that PSN is mostly influenced by vessel size (lesion-related factor), whereas PCN and PAN sensitively respond to strut-thickness (device-related factor).

Mechanism of Nucleoside Triphosphate Diphosphohydrolase-1–Associated Imbalance in Adenosine Diphosphate Degradation, B-Cell Activation, and Related Injury During Acute Antibody-Mediated Rejection

ObjectiveThe objective of this study was to investigate the effect of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) during acute antibody-mediated rejection (AMR). MethodsNTPDase1 overexpression, NTPDase1 knockout, and wild-type nude mice skin graft models were used to induce acute AMR. NTPDase1 expression in B cells, NTPDase1 messenger RNA expression in skin grafts, extracellular adenosine diphosphate (ADP) concentration, B-cell volume and surface antigens expression, average platelet transport rate, and ultrastructure and apoptosis of skin graft cells were investigated. ResultsDuring acute AMR in nude mice, higher NTPDase1 expression caused lower extracellular ADP concentration, smaller increase in B-cell volume, and major histocompatibility complex II surface antigen expression, suggesting a negative correlation between them; higher NTPDase1 expression also caused slower average platelet transport rate and less severe skin graft injury, suggesting a negative correlation between them. Pretreatment with high-dose exogenous NTPDase1 inhibited platelet activation and protected skin grafts, but it resulted in prolonged bleeding time (by 51.4%) and prolonged coagulation time (by 44.1%). ConclusionAn NTPDase1-associated imbalance in extracellular ADP degradation may contribute to B-cell activation, platelet activation, and more severe skin graft injury in nude mice. Pretreatment with high-dose exogenous NTPDase1 effectively protected skin grafts in nude mice at 1 week, but it increased the risk of bleeding.

Brain-Derived Neurotrophic Factor (BDNF) and Serotonin Transporter (SERT) in Platelets of Patients with Mild Huntington's Disease: Relationships with Social Cognition Symptoms.

Deficits in social-cognition processing have been identified during early stages of Huntington Disease (HD), attracting interest on their relevance as possible predictors of neurodegenerative progression. Since the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) and the serotonin (5-HT) transporter (SERT) are known to modulate human adaptive behavior, we appraised these two proteins in mild-HD using blood platelets, with the aim at finding relationships with cognitive/psychosocial skills. Thirteen gene positive and symptomatic patients (9M/4W, HD-stage II, age> 40y) together 11 gender/age matched controls without a concurrent diagnosis of psychiatric disorders, underwent a blood test to determine BDNF storage and membrane-bound SERT in platelets by an ELISA immune-enzyme dosage and [3H]-paroxetine ([3H]-PAR) binding, respectively. Enrolled subjects were concurrently evaluated through a battery of socio-cognitive tests and emotion recognition questionnaires.Results showed greater intra-platelet BDNF (~ +20-22%) in patients versus controls, whereas equilibrium [3H]-PAR binding parameters, maximum density (Bmax) and dissociation constant (KD), did not appreciably vary in the two comparison groups. Cognitive/emotion abilities were found significantly reduced in patients. Additionally, platelet BDNF was unrelated to psycho-cognitive scores, but positively correlated with the illness duration. As well, SERT Bmax was unconnected to HD signs or socio-cognitive scores, whilst KDs negatively correlated with scores for angry voice recognition in both controls and patients. This pilot study suggests that platelet BDNF and SERT do not specifically underlie psychosocial deficits in stage II-HD, while higher BDNF storage in delayed mild symptoms, would derive from compensatory mechanisms. Supplementary investigations are warranted, by also comparing patients in other illness's phases.