Plasma Platelet-derived Microparticles Research Articles

Surface modification of metallic materials designed for a new generation of artificial heart valves.

The main goal of this work was to develop haemocompatibile thin film materials dedicated to novel flexible mechanical heart valves intended for pulsatile ventricle assist devices. The studies performed have led to the selection of a material for the surface modification of the metallic scaffold. Haemocompatible, biofunctional, ultra-elastic, thin carbon-based coatings were proposed. The surface was designed to eliminate thrombogenic and microbial construction by a reduction in turbulence and sufficient washing of the biofunctional-adapted surfaces, thus allowing for extended use for temporary heart support. The article presents the influence of the mechanical properties of coatings and their influence on the haemocompatibility. In this study, we investigated a simplified model of the whole blood shear stress based on a cone and plate rotational viscometer. Several indices of platelet activation were analysed, including platelet and granulocyte-platelet aggregates, platelet activation markers and platelet-derived microparticles. The shear stress induced a platelet aggregate count in the range from 2% to 30% of the CD61 positive cells. For polyurethane (PU), the average value of platelet aggregates was on the level of 7%. The analyses have demonstrated that the cytometric methods of the direct determination of platelet-derived microparticles in plasma are reproducible and reliable. Considering the generation of microparticles on the tested coatings under hydrodynamic conditions, the best properties were observed for the coating a-C:H,N. The results indicate that a-C:H-based coatings with the thickness of 110 nm do not induce an immune response and do not influence the origin of platelet microparticle formation; thus, these type of coatings are the most promising for the parts which are planned to withstand blood contact under the high value of shear stress.

Relevance of elevated microparticles in peripheral blood and synovial fluid of patients with rheumatoid arthritis

Introduction: Microparticles (MPs) are submicron sized heterogeneous membrane-bound vesicles released from cells undergoing cell activation or apoptosis. Elevated platelet-derived MPs (PMPs) are reported in rheumatic diseases. We profiled Annexin-V+ MPs and CD61+ MPs in plasma and synovial fluid of patients with rheumatoid arthritis (RA) and their clinical correlates. Methods: Twenty-three newly diagnosed disease-modifying anti-rheumatic drug naive patients with RA, 17 with osteoarthritis (OA) and 22 healthy controls (HC) were enrolled. Five milliliters of synovial fluid from the knee joint of patients with RA and OA was collected; 5 ml of peripheral blood was collected from patients with RA, OA, and HC. Cell-free synovial fluid and platelet poor plasma samples were stained with Annexin-V-APC and Anti-CD61-BV510 antibodies followed by flow cytometry analysis (FACSAria III) (results expressed as the mean ± standard deviation of % population). Results: Significantly greater levels of synovial fluid MPs (Annexin-V+ MPs) were observed in RA versus OA (P Conclusions: Higher levels of Annexin-V+ MPs in both plasma and synovial fluid of RA suggest a role for MPs in the pathogenesis of RA. Elevated plasma PMPs (Annexin V+ CD61+ MPs) in RA may suggest their role in systemic involvement. Furthermore, increased levels of MPs other than those of platelet origin (Annexin V+ CD61− MPs) indicate the necessity to study the MPs from other cell lineages.

The Usefulness of Platelet-derived Microparticle as Biomarker of Antiplatelet Therapy in Kawasaki Disease.

Little is known about platelet dynamics and the effect of antiplatelet therapy in Kawasaki disease (KD). This study sought to define platelet activation dynamics in KD patients by assaying platelet-derived microparticles (PDMPs). We measured plasma PDMPs levels in 46 patients with KD using an enzyme-linked immunosorbent assay (ELISA). Blood samples were collected before, at 2–5 days, and 9–15 days after intravenous immunoglobulin (IVIG) infusion, 2 months and 4–5 months after the onset of KD. We measured PDMP levels in 23 febrile and 10 afebrile control patients. In the acute phase of KD patients, PDMP levels increased significantly after IVIG treatment (12.04 ± 5.58 nmol before IVIG infusion vs. 19.81 ± 13.21 nmol at 2–5 days after IVIG infusion, P = 0.006). PDMP levels were negatively correlated with age and positively correlated with procalcitonin levels in the acute phase of KD. No significant difference was found in PDMP levels between KD patients with and without coronary artery lesion (CAL). Elevated PDMP levels after IVIG therapy significantly decreased below the pre-IVIG level in subacute phase (19.81 ± 13.21 nmol at 2–5 days after IVIG infusion vs. 8.33 ± 2.02 nmol at 9–15 days after IVIG infusion, P < 0.001), and PDMP levels stayed below the pre-IVIG level in the convalescent phase, during which antiplatelet therapy was given. However, PDMP levels rebounded after discontinuing aspirin in 17 patients. In conclusion, enhanced platelet activation was noted before treatment of KD and peaked immediately after IVIG treatment. Recurrent rising of PDMP levels was observed after discontinuing aspirin, although there were no significant differences between the PDMP levels at 2 months after the onset of KD and those at 4–5 months after the onset of the disease.

Nanosilica based electrochemical biosensor: A novel approach for the detection of platelet-derived microparticles

Elevation of platelet-derived microparticles (PMPs) in blood plasma has a strong correlation with the pathogenesis of diseases like thrombosis, diabetes, cancer and considered as a potential biomarker. The article presents a novel method of fabrication of an electrochemical biosensor to detect PMPs in a blood using nanosilica. Electrochemically deposited thionine doped silica nanoparticles (Th@SiNPs) and horseradish peroxidase entrapped amine functionalized mesoporous silica nanoparticles (NH2-MSNs) were utilized for conjugation with antibodies recognizing active confirmation of platelet glycoprotein GPIIb/IIIa and P-selectin expressed on PMPs respectively. Cyclic voltammetric analysis showed a progressive increase in reduction peak current on PMPs binding with the fabricated electrode in the presence of peroxide. The response of the sensor was linear in the range from 490 to 4080PMPsμL−1 and could detect PMPs with a detection limit of ∼96PMPsμL−1. The developed sensor proved to be highly specific in identifying PMPs in plasma and offers highly biocompatible, label-free, cost-effective, ease of miniaturization, short analysis time and simple instrumentation for the detection of biomarkers for a variety of diseases. The novel sensor is expected to find widespread applications in clinical point-of-care testing

Platelet microparticles inhibit IL-17 production by regulatory T cells through P-selectin

AbstractSelf-tolerance and immune homeostasis are orchestrated by FOXP3+ regulatory T cells (Tregs). Recent data have revealed that upon stimulation, Tregs may exhibit plasticity toward a proinflammatory phenotype, producing interleukin 17 (IL-17) and/or interferon γ (IFN-γ). Such deregulation of Tregs may contribute to the perpetuation of inflammatory processes, including graft-versus-host disease. Thus, it is important to identify immunomodulatory factors influencing Treg stability. Platelet-derived microparticles (PMPs) are involved in hemostasis and vascular health and have recently been shown to be intimately involved in (pathogenic) immune responses. Therefore, we investigated whether PMPs have the ability to affect Treg plasticity. PMPs were cocultured with healthy donor peripheral blood–derived Tregs that were stimulated with anti-CD3/CD28 monoclonal antibodies in the presence of IL-2, IL-15, and IL-1β. PMPs prevented the differentiation of peripheral blood–derived Tregs into IL-17– and IFN-γ–producing cells, even in the presence of the IL-17–driving proinflammatory cytokine IL-1β. The mechanism of action by which PMPs prevent Treg plasticity consisted of rapid and selective P-selectin–dependent binding of PMPs to a CCR6+HLA-DR+ memory-like Treg subset and their ability to inhibit Treg proliferation, in part through CXCR3 engagement. The findings that ∼8% of Tregs in the circulation of healthy individuals are CD41+P-selectin+ and that distinct binding of patient plasma PMPs to Tregs was observed support in vivo relevance. These findings open the exciting possibility that PMPs actively regulate the immune response at sites of (vascular) inflammation, where they are known to accumulate and interact with leukocytes, consolidating the (vascular) healing process.

Association of the Plasma Platelet-Derived Microparticles to Platelet Count Ratio with Hospital Mortality and Disseminated Intravascular Coagulopathy in Critically Ill Patients.

The role of platelet-derived microparticles (PDMPs) in the crosstalk between coagulopathy and inflammation in critically ill patients remains unclear. The aim of this cohort observational study was to investigate the associations between the PDMP levels and hospital mortality or disseminated intravascular coagulopathy (DIC). This study included 119 patients who were admitted to the ICU. The PDMP levels were measured using an enzyme-linked immunosorbent assay three times a week, for a total of 372 samples. We calculated the maximum (max) PDMP value, max PDMP/platelet (PDMP/Plts) ratio (converted to the PDMP levels per 10(4) platelets) and nadir platelet count during the ICU stay. Baseline patient data and scores, including the Japanese Association for Acute Medicine (JAAM) DIC score, were collected, and potential predictors were analyzed for possible associations with hospital mortality. The max PDMP/Plts ratio was significantly different comparing the survivors (n=98: median, 2.54) and non-survivors (n=21: median 17.59; p＜0.001). There was a weak but statistically significant negative correlation between the max PDMP level and nadir platelet count (r=-0.332, p＜0.001). The max PDMP level and max PDMP/Plts ratio were higher in the DIC group (81.48 and 9.27, respectively) than in the non-DIC group (34.88 and 2.35, p=0.001 and p＜0.001, respectively). The max PDMP/Plts ratio was the only variable found to be independently associated with hospital mortality according to a multivariate logistic regression analysis. PDMPs are involved in the development of DIC but are not related to hospital mortality. There is a good association between the PDMP/Plts ratio and hospital mortality and/or DIC in critically ill patients.

Elevated RANTES level is associated with metabolic syndrome and correlated with activated platelets associated markers in healthy younger men.

The objective of this study was to clarify the relationship of regulated on activation normal T cell expressed and secreted (RANTES) levels with metabolic syndrome (MS) and activated platelets-associated markers. We conducted a cross-sectional study of 210 healthy Japanese male volunteers (mean age 41 years old) who did not take any medications and were free of cardiovascular or cerebrovascular disease. The RANTES is correlated with age, diastolic blood pressure, and fast glucose by multivariate analysis using the cardiovascular risk factors (R (2) = .396, P < .001). The plasma RANTES level is significantly associated with MS after adjusting for age (P = .040). Once plasma interleukin 6, an activator of platelets, and plasma platelet-derived microparticles, a marker for activated platelets, are put into the equation, plasma RANTES level is significantly correlated with the activated platelet-associated markers (R (2) = .396, P < .001). These suggest the possible role of elevated RANTES in the forerunner of atherosclerosis in healthy younger men.

Protein S and factor V in regulation of coagulation on platelet microparticles by activated protein C

IntroductionPlatelets are the main source of microparticles in plasma and the concentration of microparticles is increased in many diseases. As microparticles expose negatively charged phospholipids, they can bind and assemble the procoagulant enzyme-cofactor complexes. Our aim was to elucidate possible regulation of these complexes on microparticles by the anticoagulant protein C system. Materials and methodsPlatelets were activated with thrombin±collagen or the calcium ionophore A23187±thrombin to generate microparticles. The microparticles were analyzed using flow cytometry and functional coagulation assays to characterize parameters with importance for the activated protein C system. ResultsActivation with A23187+thrombin was most efficient, fully converting the platelets to microparticle-like vesicles, characterized by high lactadherin and protein S binding capacity. Suppression of thrombin generation by activated protein C in plasma spiked with these microparticles was dependent on the presence of plasma protein S. Experiments with purified components showed that activated protein C inhibited both factor Va and factor VIIIa on the microparticle surface. Inhibition of factor Va was stimulated by, but not fully dependent on, the presence of protein S. In the factor VIIIa-degradation, activated protein C was dependent on the addition of protein S, and exogenous factor V further increased the efficiency. ConclusionsProtein S is crucial for activated protein C-mediated inhibition of thrombin generation on platelet-derived microparticles in plasma. Moreover, protein S and factor V are synergistic cofactors in the inhibition of factor VIIIa. The results demonstrate that the activated protein C system has the capacity to counterbalance the procoagulant ability of microparticles.

Plasma platelet-derived microparticles to platelet count ratio as marker of non-survivor in critically ill patients

Plasma platelet-derived microparticles to platelet count ratio as marker of non-survivor in critically ill patients

Plasma platelet-derived microparticles to platelet count ratio as a marker of mortality in critically ill patients

While the crosstalk between coagulopathy and inflammation plays a key role in the development of multiple organ dysfunction in critically ill patients, the mechanisms governing this crosstalk have yet to be established. Microparticles (MPs) are submicron vesicles shed from a variety of cells that are considered to have proinflammatory and prothrombotic properties. Although platelet- derived MPs (PDMPs) are the main form of MPs, the role of PDMPs in critically ill patients remains unclear [1]. The aims of this study were to investigate serum PDMP levels in critically ill patients and to assess their prognostic value.

Platelet-derived microparticles in overweight/obese women with the polycystic ovary syndrome

A substantial proportion of women with the polycystic ovary syndrome (PCOS) are obese and obesity is considered as a prothrombotic state. Platelet-derived microparticles (PMPs) might be implicated in the activation of the coagulation cascade. We aimed to assess plasma PMPs in overweight/obese women with PCOS. We measured plasma PMPs and determined anthropometric, metabolic, hormonal and ultrasonographic features of PCOS in 67 overweight/obese women with PCOS (with body mass index [BMI] >25.0 kg/m2) and in 21 BMI-matched healthy women. Circulating androgens and markers of insulin resistance (IR) were higher in women with PCOS than in controls. Plasma PMPs were also higher in women with PCOS than in controls (p = 0.046). In women with PCOS, plasma PMPs correlated with the mean number of follicles in the ovaries (r = 0.343; p = 0.006). In controls, plasma PMPs did not correlate with any of the studied parameters. In conclusion, plasma PMPs are elevated in overweight/obese women with PCOS compared with BMI-matched controls. The cause of this increase is unclear but both IR and hyperandrogenemia might be implicated. More studies are required to elucidate the pathogenesis of the elevation of PMPs in PCOS and to assess its implications on the cardiovascular risk of these patients.

Effects of pitavastatin on plasminogen activator inhibitor-1 in hyperlipidemic patients

The effects of statins on two platelet activation markers, plasiminogen activator inhibitor (PAI)-1 and adiponectin, were investigated in 68 patients with hyperlipidemia. The patients were treated with pitavastatin with a dosage of 2 mg daily. The plasma levels of platelet-derived microparticles (PDMP), soluble CD40 ligand (sCD40L), sP-selectin, PAI-1, and adiponectin were measured at baseline and after 6 months of treatment in both groups. In hyperlipidemic patients, the plasma levels were higher in PDMP, sCD40L, sP-selectin, and PAI-1, and lower in adiponectin, compared to the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, while plasma adiponectin was negatively correlated with the plasma levels of PAI-1. No significant differences were observed in the plasma levels of PDMP, sCD40L, sP-selectin, and PAI-1 before and after treatment. A significant increase in plasma adiponectin levels was observed after 6 months of treatment with pitavastatin. When the patients treated with pitavastatin were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases in plasma PAI-1, PDMP, and sCD40L levels were observed after pitavastatin treatment in the responder group. These findings suggest that PDMP, sCD40L, and PAI-1 may participate in the development of atherothrombosis in patients with hyperlipidemia, and that pitavastatin may exert an adiponectin-dependent anti-atherothrombotic effect in hyperlipidemic patients.

Effects of miglitol in platelet-derived microparticle, adiponectin, and selectin level in patients with type 2 diabetes mellitus

Background:Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Miglitol has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on platelet activation markers (PDMP and soluble CD40 ligand [sCD40L]), selectins, and adiponectin in these patients is poorly understood.Aim:We investigated the effect of miglitol on circulating levels of PDMP, sCD40L, selectins, and adiponectin in patients with type 2 diabetes.Methods:Miglitol (150 mg/day) was administered for 4 months. Levels of PDMP, sCD40L, soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), soluble L-selectin (sL-selectin), and adiponectin were measured by enzyme-linked immunosorbent assay at baseline, and after 1 and 4 months of treatment.Results:The levels of PDMP, sCD40L, sP-selectin, sE-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients, while there were no significant differences between hypertensive and hyperlipidemic patients. Before miglitol treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Miglitol therapy significantly decreased the plasma PDMP and sCD40L levels relative to baseline. Miglitol also caused a significant decrease of sP-selectin, sE-selectin, and sL-selectin. On the other hand, miglitol therapy led to a significant increase in adiponectin after 4 months of administration compared with baseline. Furthermore, the reduction of platelet activation markers and selectins during miglitol therapy was significantly greater in the responder (adiponectin-improved) group than the nonresponder group of diabetic patients.Conclusion:Miglitol has an adiponectin-dependent anti-atherothrombotic effect that may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes.

Circulating platelet-derived microparticles are elevated in women with polycystic ovary syndrome diagnosed with the 1990 criteria and correlate with serum testosterone levels

Women with polycystic ovary syndrome (PCOS) appear to have higher cardiovascular risk than healthy population. Patients diagnosed with PCOS according to the 1990 criteria have a more adverse metabolic profile than those diagnosed with the 2003 criteria. Platelet-derived microparticles (PMPs) appear to contribute to atherosclerosis but have not been assessed in PCOS. The aim of this study was to determine plasma PMPs in PCOS patients. Design A cross-sectional study. We assessed plasma PMPs in 76 normal weight women with PCOS (39 belonging to the phenotypes 1 and 2 (group I) and 37 belonging to the phenotypes 3 and 4 (group II)) and 21 healthy normal weight women. Markers of obesity and insulin resistance did not differ between women with PCOS and controls. Serum testosterone levels and the free androgen index (FAI) were higher in group I than in group II and controls (P<0.001 for all comparisons) but did not differ between the latter two groups. Plasma PMPs were higher in group I than in controls (P=0.018) but did not differ between group II and controls or between groups I and II. In the total study population (n=97), plasma PMPs correlated with serum testosterone levels (r=0.207, P=0.042) and the FAI (r=0.207, P=0.042). Plasma PMPs are elevated in women with phenotypes 1 and 2 of PCOS compared with healthy controls, but not in women with phenotypes 3 and 4. Hyperandrogenemia, which is more pronounced in phenotypes 1 and 2, appears to be implicated in the increase in plasma PMPs.

Plasma Platelet-derived Microparticles in Patients with Connective Tissue Diseases

To clarify the role of platelet-derived microparticles (PDMP), which are small vesicles with thrombotic and immunological properties, in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis/polymyositis (PM/DM), and mixed connective tissue disease (MCTD). Plasma levels of PDMP were measured by ELISA, and compared among patients with one of the 4 diseases. Association of PDMP levels with clinical characteristics and medication of the patients was also examined. PDMP levels were higher in patients with MCTD and SSc than in controls. Multiple linear regression analysis revealed that patients with Raynaud's phenomenon (RP) showed higher PDMP levels than those without. PDMP levels in individual patients did not fluctuate significantly over several months. PDMP level is associated with MCTD, SSc, and RP, and could be a novel marker for RP.

Correlation and association of plasma interleukin-6 and plasma platelet-derived microparticles, markers of activated platelets, in healthy individuals

Intorduction The aim of this study was to clarify the correlation and association of plasma IL-6 and PDMPs, both of which are associated with metabolic syndrome, in healthy individuals. Materials and Methods We conducted a cross-sectional study of 464 healthy Japanese volunteers (210 men and 254 women, median age 39 and 35 years, respectively) who had no signs, symptoms or history of cardiovascular- or cerebrovascular disease and took no medications. We assayed their IL-6 levels with a conventional ELISA kit and their PDMP levels by ELISA and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX). Results By multivariate analysis, the plasma level of PDMP was correlated with diastolic blood pressure (p = 0.015), platelet count (p < 0.001), high sensitivity C-reactive protein, and the plasma level of IL-6 (p < 0.001) in men (R 2 = 0.454, p < 0.001) and was correlated with platelet count (p < 0.001) and the plasma level of IL-6 (p < 0.001) in women (R 2 = 0.159, p < 0.001). Quartile range of plasma level of IL-6 was associated with plasma level of PDMP after adjustment for diastolic blood pressure, platelet count, and high sensitivity C-reactive protein in men (p < 0.001) and associated with plasma level of PDMP after adjustment for platelet count in women (p < 0.001). Conclusions These results suggest the plasma IL-6 is correlated and associated with the plasma PDMPs, markers of activated platelets in healthy individuals.

Platelet activation in patients with psoriasis: Increased plasma levels of platelet-derived microparticles and soluble P-selectin

It has recently been established that platelets have an important role in increasing inflammation, in addition to their main role in hemostasis and thrombosis. An increased incidence of occlusive vascular disease has been reported in patients with psoriasis and the pathomechanism of psoriasis may involve platelet activation. The goal of the study was to establish a clearer explanation of the association between platelet activation and psoriasis activity by investigating the levels of markers of platelet activation in patients with psoriasis and examining the relationship between the marker levels and a severity score for psoriasis. Plasma levels of platelet-derived microparticles (PDMPs) and soluble P-selectin were measured by enzyme-linked immunosorbent assay as markers of platelet activation in 21 patients with psoriasis and 22 healthy control subjects. The relationships between the platelet activation markers and the Psoriasis Area and Severity Index score were investigated. Plasma PDMPs and soluble P-selectin levels were markedly higher in patients with psoriasis compared with those in healthy control subjects. There was a significant correlation between the PDMPs levels and the Psoriasis Area and Severity Index score, and the increased plasma PDMPs and soluble P-selectin levels were markedly reduced after clinical improvement occurred. The number of people evaluated was relatively small. Our results show that blood platelets are activated in patients with psoriasis, especially in those with extensive disease, and suggest a close association between platelet activation and psoriasis activity. Plasma PDMPs level may be a useful indicator of the severity of psoriasis.

Effects of pitavastatin on monocyte chemoattractant protein-1 in hyperlipidemic patients

The effects of statins on platelet activation markers, chemokines and adiponectin, were investigated in 135 patients with hyperlipidemia. Of the 135 hyperlipidemic patients, 63 were allocated to the simvastatin group, treated with simvastatin at the dose of 10 mg daily, and the remaining 72 were allocated to the pitavastatin group, treated with pitavastatin at the dose of 2 mg daily. Plasma levels of platelet-derived microparticles (PDMP), cell adhesion molecules (sCD40L and sP-selectin), chemokines [monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normally T-cell expressed and secreted] and adiponectin were measured at the baseline and after 6 months of treatment in both the groups. In addition, we carried out a basic study to investigate the MCP-1-dependent induction of tissue factor expression on a histiocytic cell line (U937 cells). The plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 were higher, whereas those of adiponectin were lower, in the hyperlipidemic patients than in the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, whereas plasma adiponectin was negatively correlated, with the plasma levels of MCP-1. No significant differences in the plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 measured before and after treatment were observed in either the simvastatin or pitavastatin group. A significant increase of the plasma adiponectin levels was observed after 6 months of treatment with pitavastatin but not after an equal duration of treatment with simvastatin. When pitavastatin-treated patients were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases of the plasma MCP-1, PDMP and sCD40L levels were observed after pitavastatin treatment in the responder group. In the aforementioned basic study, MCP-1 by itself did not induce the expression of tissue factor on the U937 cells. However, the recombinant sCD40L-induced expression of tissue factor on U937 was enhanced by the addition of MCP-1. These findings suggest that PDMP, sCD40L and MCP-1 may participate in the development of atherothrombosis in patients with hyperlipidemia and that pitavastatin may exert an adiponectin-dependent antiatherothrombotic effect in hyperlipidemic patients.

Platelet-derived microparticles and soluble P-selectin as platelet activation markers in patients with atopic dermatitis

Plasma levels of platelet-derived microparticles (PDMPs) and soluble P-selectin (sP-selectin) were investigated as markers of platelet activation in 46 atopic dermatitis (AD) patients, 20 non-atopic urticaria patients and 22 healthy controls. The relationships between these markers and the scoring AD (SCORAD) index, blood eosinophil number, serum IgE, and serum lactate dehydrogenase were also investigated in AD patients. Plasma PDMPs and sP-selectin levels were significantly higher in AD patients compared with the other two groups. In multiple regression analysis, the SCORAD index was the most significant factor associated with the platelet activation markers. Among the SCORAD index components, excoriations were most closely related to the markers. The elevated levels of PDMPs and sP-selectin were significantly reduced following skin lesion improvement by drug treatment. Our results show that blood platelets are activated in AD patients upon aggravation of eruption, suggesting that activated platelets may be involved in the pathomechanism of AD.

Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients

Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Acarbose has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on PDMP, selectins, and adiponectin in these patients is poorly understood. We investigated the effect of acarbose on circulating levels of PDMP, selectins, and adiponectin in patients with type 2 diabetes. Acarbose (300 mg/day) was administered for 3 months. Levels of PDMP, sP-selectin, sL-selectin, and adiponectin were measured by ELISA at baseline and after 1 and 3 months of treatment. The levels of PDMP, sP-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients (PDMP; 35.1 +/- 34.2 vs. 53.3 +/- 56.7 U/ml, P < 0.05: sP-selectin; 134 +/- 52 vs. 235 +/- 70 ng/dl, P < 0.01: sL-selectin; 569 +/- 183 vs. 805 +/- 146 ng/ml, P < 0.05), while there were no significant differences between hypertensive and hyperlipidemic patients. Before acarbose treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Acarbose therapy significantly decreased the plasma PDMP level relative to baseline. Acarbose also caused a significant decrease of sP-selectin and sL-selectin. On the other hand, acarbose therapy led to a significant increase of adiponectin after 3 months of administration compared with baseline (adiponectin: diabetes versus hypertension, 3.61 +/- 1.23 vs. 5.87 +/- 1.92 microg/ml, P < 0.05; diabetes versus controls, 2.81 +/- 0.95 vs. 6.13 +/- 1.24 microg/ml, P < 0.01). Twelve of the 30 diabetic patients had a history of thrombotic complications. Furthermore, the reduction of PDMP and selectins during acarbose therapy was significantly greater in the thrombotic group (12 of 30) than in the nonthrombotic group (18 of 30) of diabetic patients. Acarbose may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes. However, it requires a large clinical trial to test this hypothesis.