The aim of this study was to investigate possible pathomechanisms behind the cardiovascular morbidity caused by inhalation
of particulate matter (PM10). For that purpose, healthy volunteers were exposed to high PM10 concentrations during a 2 h hay storing activity. Blood was drawn in the evening before and after PM10 exposure and in the morning and evening of the day after exposure. The leukocyte count increased after PM10 exposure with an initial increase of segmented neutrophils followed by banded forms. C-reactive protein increased over time. Fibrinogen and plasma viscosity became increased in the evening of the day after PM10 exposure. Platelet aggregation was increased in the evening after PM10 exposure. At the same time von Willebrand factor and factor VIII were increased, reflecting endothelial activation. These
results confirm that acute inhalative exposure to high PM10 concentrations during hay storage activity leads to a systemic inflammatory reaction, endothelial activation, and platelet
aggregation. 相似文献
Background Platelets play a pivotal role in the pathogenesis of the thrombotic complications in cardiovascular disease (CVD). Abnormal
platelet activation indices are evolving as potentially useful markers in CVD risk stratification. Whilst there has been some
investigation into the effects of storage time on several of these indices, the effects of underlying disease severity on
these temporal changes have not been previously studied.
Methods Using the ADVIATM120 haematology analyser, we assessed the effects of time-dependent storage of whole blood in EDTA, on a number of platelet
activation indices: mean platelet volume (MPV), mean platelet component (MPC, measure of platelet density) and platelet component
distribution width (PCDW, a marker of platelet shape change. We studied three age- and sex-matched patient groups: (i) healthy
controls (n = 10), (ii) stable patients with coronary artery disease (CAD, n = 9); and (iii) patients with acute myocardial infarction (n = 8). Whole blood samples were processed at exactly 5 min following venesection and at 15, 30, 60 and 120 min later in storage
in EDTA tubes at room temperature.
Results There was a significant and stepwise increase in MPV (P = 0.01) and decrease in PCDW (P = 0.03), with a non-significant trend to increasing MPM and decreasing MPC with increasing underlying disease (that is healthy,
‘stable’ and ‘acute’ artery disease). There was a significant time-dependent increase in MPV and decrease in MPC and PCDW
(all P < 0.05), which were all significant on ‘post-hoc’ analyses by 30 min. There were no significant changes in platelet count
or MPM with time. There was no interaction of underlying disease with whole-blood storage time for any of the platelet indices
reported (P = NS).
Conclusion There is a temporal increase in MPV and decrease in MPC and PCDW in venous blood stored over 2 h in EDTA. These changes are
not influenced by the underlying CVD disease severity. 相似文献
Summary High speed centrifugation allows separation of whole blood into cell free plasma, a buffy coat and leukocyte poor red cells. The buffy coat can be used for the preparation of platelet concentrates. High lactate production at 22°C requires storage of the buffy coat at 4°C. Survival in vivo of platelet concentrates prepared from buffy coats stored at 4°C for 48 h (BC-PC) was compared with the survival in vivo of platelet concentrates from platelet rich plasma stored at 22°C for 48 h (PRP-PC). Both methods were studied in the same healthy volunteers (n=8) using51Cr labeled autologous platelets. The mean ±SD recovery 15 min after reinfusion of the BC-PC was 30.5%±13.3% and for PRP-PC 41.4%±7.9% (p<0.0001). The survival in vivo for BC-PC was 2.4 days ±0.4 days and for PRP-PC 7.0 days ±1.4 days (p<0.0001).Since the survival in vivo is significantly less for platelets derived from the buffy coat stored at 4°C, we advocate storage of platelets at 22°C. 相似文献
Platelets and their granular contents influence both angiogenesis and breast cancer progression. This study was performed to assess the effect of breast cancer and its treatment on platelet biology and the response to inhibition of the platelet P2Y12 receptor. Receptor-specific platelet activation and inhibition was studied for three platelet-associated proteins important in cancer angiogenesis and progression, vascular endothelial growth factor (VEGF), thrombospondin1 (TSP1), and transforming growth factor beta 1 (TGF-β1).
Twenty-four women with active breast cancer and 10 healthy controls not receiving antiplatelet therapy participated in the study. Ex vivo activation of platelets in whole blood was accomplished using PAR1AP, PAR4AP, convulxin, and ADP. Platelet inhibition was accomplished using the P2Y12 receptor antagonist cangrelor (the in vitro equivalent of clopidogrel). VEGF, TSP1, and TGF-β1 were measured using standard ELISA.
Platelet activation by ADP, PAR1, PAR4, and collagen receptors increased VEGF, TSP1, and TGF-β1 secretion in patients with breast cancer. Agonist-induced release of VEGF was greater in cancer patients as compared to healthy controls (p = 0.02 for ADP, p < 0.001 for PAR1AP, PAR4AP, and convulxin) despite a decrease in the efficiency of VEGF secretion in patients with breast cancer. These differences were not observed for TSP1 and TGF-β1 secretion. P2Y12 receptor inhibition decreased VEGF, TSP1, and TGF-β1 secretion. In patients with cancer, cangrelor inhibited TSP1 release to a greater extent than VEGF and TGF-β1 release. In patients with breast cancer, the magnitude of platelet inhibition achieved by cangrelor was greater than that achieved with healthy controls for all agonists and platelet proteins studied.
While platelets are known to influence progression of breast cancer, our results show that breast cancer and its treatment influence the platelet phenotype by increasing the secretion of pro-angiogenic proteins following platelet activation, modulating the efficiency of platelet protein release as well as increasing the response to antiplatelet therapy. 相似文献
BACKGROUND: The beneficial effect of moderate alcohol consumption in lowering the risk of cardiovascular disease has been shown in several epidemiologic studies. Such studies have also shown, however, that the protective effect of alcoholic beverages like wine and beer is not only due to the ethanol content but also to the presence of nonalcoholic constituents. The positive effect of alcoholic beverages has been attributed to changes in lipoprotein metabolism, but there is substantial evidence that effects on hemostasis play an important role. Whether the effects of alcoholic beverages on hemostasis are due exclusively to ethanol or are due, in part, to nonalcoholic components, is still under debate. METHODS: We have examined the hemostatic effects of 3 liters of beer, dealcoholized beer, and ethanol/water (v/v 4%), consumed over a period of 3 hr, in 12 young healthy volunteers. Platelet parameters CD62, PAC-1, and monocyte platelet aggregates were analyzed using flow cytometric measurements. The activity of factor VII was determined with a prothrombin time (PT) assay and plasminogen activator inhibitor activity using a chromogenic substrate. Thrombin generation was determined according to the method of Hemker. RESULTS: All three fluids administered, dealcoholized beer, beer, and ethanol, reduced the expression of activated fibrinogen receptor, the platelet activation marker CD62, and the formation of monocyte-platelet-aggregate. In addition, dealcoholized beer also showed significant inhibitory effects on thrombin generation, whereas beer and ethanol showed procoagulatory effects. CONCLUSIONS: This study has shown that the acute consumption of dealcoholized beer inhibits thrombogenic activity in young adults. This action could have a beneficial effect on the development of coronary artery disease. Thus, the consumption of dealcoholized beer could provide cardiovascular benefit without the negative effects of alcohol. 相似文献
Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (−37%, P<0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH patients were combined (r=−0.48, P=0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r=−0.59, P=0.03; normal and FH data, r=−0.49, P=0.004) but positively with high-density lipoprotein (HDL) (FH, r=0.79, P=0.001; normal and FH, r=0.37, P=0.03). Collagen (5–160 μg/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 μg/ml collagen, −40%, P<0.05) and accompanied by increased collagen EC50 values (P<0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH. 相似文献