Preclinical Evaluation of Safety and Biodistribution of Red Cell Microparticles: A Novel Hemostatic Agent.

Background: Uncontrollable bleeding is a major cause of mortality and morbidity worldwide. Effective hemostatic agents are urgently needed. Red cell microparticles (RMPs) are a highly promising hemostatic agent.

Pharmacokinetics of Human Red Blood Cell Microparticles Prepared Using High-Pressure Extrusion Method.

Red blood cell microparticles (RMPs) is a high potency hemostatic agent, which may serve as a viable therapeutic approach. They generate thrombin and effective in arresting bleeding in animal bleeding models. However, prior to ascertaining the clinical efficacy of RMPs, detailed preclinical evaluation is necessary.

Why, when and how should exposure be considered at the within-host scale? A modelling contribution to PRRSv infection.

Understanding the impact of pathogen exposure on the within-host dynamics and its outcome in terms of infectiousness is a key issue to better understand and control the infection spread. Most experimental and modelling studies tackling this issue looked at the impact of the exposure dose on the infection probability and pathogen load, very few on the within-host immune response. Our aim was to explore the impact on the within-host response not only of the exposure dose, but also of its duration and peak, for contrasted virulence levels.

Modelling Salmonella transmission among pigs from farm to slaughterhouse: Interplay between management variability and epidemiological uncertainty.

Salmonella carriage and cutaneous contamination of pigs at slaughter are a major risk for carcass contamination. They depend on Salmonella prevalence at farm, but also on transmission and skin soiling among pigs during their journey from farm to slaughterhouse. To better understand and potentially control what influences Salmonella transmission within a pig batch during this transport and lairage step, we proposed a compartmental, discrete-time and stochastic model.

Integrative model of the immune response to a pulmonary macrophage infection: what determines the infection duration?

The immune mechanisms which determine the infection duration induced by pathogens targeting pulmonary macrophages are poorly known. To explore the impact of such pathogens, it is indispensable to integrate the various immune mechanisms and to take into account the variability in pathogen virulence and host susceptibility. In this context, mathematical models complement experimentation and are powerful tools to represent and explore the complex mechanisms involved in the infection and immune dynamics.

Red cell-derived microparticles (RMP) as haemostatic agent.

Among circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP.

Neuromonitoring with microdialysis in severe traumatic brain injury patients.

Background: Neuromonitoring with microdialysis has the potential for early detection of metabolic derangements associated with TBI.

Methods: 1,260 microdialysis samples from 12 TBI patients were analyzed for glucose, -lactate, pyruvate, lactate/pyruvate ratio (LPR), and lactate/glucose ratio (LGR). Analytes were correlated with the Glasgow Coma Scale (GCS) before surgery and with the Glasgow Outcome Scale (GOS) at the time of discharge.

Fat-free mass predictions through a Bayesian Network enable body composition comparisons in various populations.

The respective contribution of fat-free mass (FFM) and fat mass to body weight (Wgt) is a relevant indicator of risk for major public health issues. In an earlier study, a Bayesian Network (BN) was designed to predict FFM from a DXA database (1999-2004 NHANES, n = 10,402) with easily accessible variables [sex, age, Wgt, and height (Hgt)]. The objective of the present study was to assess the robustness of these BN predictions in different population contexts (age, BMI, ethnicity, etc.

Bilateral ballism following streptococcal infection, associated with psychiatric disorder and purpura.

A woman in her 30s was brought to the hospital with abnormal movements. Three months prior, the patient had exacerbation of the movements after an episode of recurrent pharyngitis. Neurological examination revealed, violent involuntary movement that affected both upper and lower limbs, hypotonia and ataxia.

Body composition predicted with a Bayesian network from simple variables.

The relative contributions of fat-free mass (FFM) and fat mass (FM) to body weight are key indicators for several major public health issues. Predictive models could offer new insights into body composition analysis. A non-parametric equation derived from a probabilistic Bayesian network (BN) was established by including sex, age, body weight and height.

Potential roles of cell-derived microparticles in ischemic brain disease.

Purpose: The objective of this study is to review the role of cell-derived microparticles in ischemic cerebrovascular diseases.

Materials And Methods: An extensive PubMed search of literature pertaining to this study was performed in April 2009 using specific keyword search terms related to cell-derived microparticles and ischemic stroke. Some references are not cited here as it is not possible to be all inclusive or due to space limitation.

Antiphospholipid antibodies: paradigm in transition.

Objectives: This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP.

Microparticle-mediated thrombin generation assay: increased activity in patients with recurrent thrombosis.

Background: Circulating cell-derived microparticles (MP) are important players in thrombogenesis, attributed in part to tissue factor (TF) carried on them. We developed MP-mediated thrombin generation assay (TGA) and measured a series of patients with thrombosis (TBS) and normal controls (NC).

Methods: MP were isolated from plasma of 66 patients with TBS and 34 NC.

Mathematical modeling of T-cell activation kinetic.

T-cell activation is a crucial step in mounting of the immune response. The dynamics of T-cell receptor (TCR) specific recognition of peptide presented by major histocompatibility complex (MHC) molecule decides the fate of the T cell. Several biochemical interactions interfere resulting in a highly complex mechanism that would be difficult to understand without computer help.

Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study.

Background: The presence of antiphospholipid antibodies (APLA) in multiple sclerosis (MS) patients has been reported frequently but no clear relationship between APLA and the clinical and neuroimaging features of MS have heretofore been shown. We assessed the clinical and neuroimaging features of MS patients with plasma APLA.

Methods: A consecutive cohort of 24 subjects with relapsing-remitting (RR) MS were studied of whom 7 were in remission (Rem) and 17 in exacerbation (Exc).

Platelet activation rather than endothelial injury identifies risk of thrombosis in subjects positive for antiphospholipid antibodies.

Background: Anti-phospholipid antibodies (APLA) are often associated with thrombosis, defining the antiphospholipid syndrome (APS) but it remains unclear why many subjects who are positive for APLA chiefly anti-cardiolipin (aCL) or anti-beta2GPI (abeta2GPI) do not develop thrombosis. A related question addressed in this study is whether the target of cellular injury in APS is predominately platelets or endothelial cells (EC).

Methods: aCL and abeta2GPI were determined by ELISA in 88 patients, 60 of whom were thrombotic and 28 non-thrombotic.

Cell-derived microparticles and exosomes in neuroinflammatory disorders.

All blood cells and the vascular endothelium shed microparticles (MP) from their plasma membranes when suitably stimulated, and assay of MP in patient blood has found increasing application to the monitoring of disease states. In addition, mounting evidence suggests that MP are not mere epiphenomena but play significant roles in the pathophysiology of thromboses, inflammation, and cancers. This chapter endeavors to summarize the limited number of studies thus far done on MP in neurological disorders such as multiple sclerosis (MS), transient ischemic attacks, and the neurological manifestations of antiphospholipid syndrome (APS).

Platelet activation in Helicobacter pylori-associated idiopathic thrombocytopenic purpura: eradication reduces platelet activation but seldom improves platelet counts.

Introduction: It has been suggested that Helicobacter pylori eradication often increases platelet counts in patients with chronic idiopathic thrombocytopenic purpura (ITP). In addition, H. pylori has been shown to induce platelet activation (CD62p or P-selectin expression) in previous studies.

Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS).

Antiphospholipid antibodies (APLA) are associated with anti-phospholipid syndrome (APS), a thrombotic disorder, but they are also frequently detected in immune thrombocytopenic purpura (ITP), a bleeding disorder. To investigate possible differences of APLA between these two disorders, we assayed IgG and IgM APLA by ELISA in 21 patients with ITP and 33 with APS. The APLA reacting against two protein target antigens, beta(2)-glycoprotein 1 (beta2GP1) and FVII/VIIa, and four phospholipids [cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE)] as well as lupus anticoagulant (LA) were analyzed.

Antiphospholipid antibodies and platelet activation as risk factors for thrombosis in thrombocythaemia.

Introduction: Risk factors for thrombosis (TB) in thrombocythaemia (TC) associated with myeloproliferative disorder (MPD) are not well defined.

Methods: We measured antiphospholipid antibodies (APLA) in 35 patients with TC associated with MPD. Fourteen had TB and 21 did not.

Life-threatening hypercoagulable state following splenectomy in ITP: successful management with aggressive antithrombotic therapy and danazol.

A life-threatening hypercoagulable state (HCS) is reported that developed after splenectomy in idiopathic thrombocytopenic purpura (ITP). A 50-year-old active male was rejected for blood donation because of an incidental finding of low platelet counts, 40,000/uL. The diagnosis was ITP.

Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation.

Endothelial microparticles (EMP) released from activated or apoptotic endothelial cells (EC) are emerging as useful markers for detection of EC dysfunction. Our recent observation that EMP carry von Willebrand factor (vWf) led us to investigate their interaction with platelets. EMP were incubated with normal washed platelets in the presence or absence of ristocetin, then platelet aggregates were measured by flow cytometry.

Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy.

Rituximab, a chimeric monoclonal CD20 antibody, is useful in the treatment of B-cell lymphomas and certain autoimmune diseases. We report a successful outcome of rituximab for life threatening hypercoagulable state associated with lupus anticoagulant (LA). A 30-year-old woman initially presented 10 years ago with DVT and positive serology for SLE and LA.

Antiphospholipid antibodies in immune thrombocytopenic purpura tend to emerge in exacerbation and decline in remission.

Although the presence of antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) has been reported, their clinical significance is not clear. The present study investigated APLA profiles in relation to the clinical stages of ITP. We studied APLA in 40 patients in three stages of ITP: exacerbation/relapse (n=7), stable (n=14) and remission (n=19).