[FUNCTIONAL DISORDERS OF BLOOD PLATELETS].
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The interrelationship of antibodies directed against cardiolipin (CL), double stranded DNA (dsDNA), endothelial cells (EC) and blood platelets was investigated. IgG fractions, reactive with these antigens, were isolated from the plasmas from 8 patients with systemic lupus erythematosus and tested for crossreactivity with anionic phospholipids (CL, phosphatidylserine, phosphatidylinositol), zwitterionic phospholipids (phosphatidylethanolamine, phosphatidylcholine), dsDNA, EC and platelets by enzyme-linked immunosorbent assays and for lupus anticoagulant (LAC) activity with a coagulation assay. Our results demonstrate the frequent occurrence of crossreactivity between antibodies to anionic phospholipids, EC and platelets. Crossreactivities between these antibodies and antibodies to dsDNA or zwitterionic phospholipids are exceptional. LAC activity was found in the anti-CL, anti-EC and anti-platelet fractions of only one patient. These findings support the hypothesis that subpopulations of antibodies directed against negatively charged phospholipids can bind to EC and blood platelets, which may have implications for the pathogenetic potential of antiphospholipid antibodies.
5-Hydroxytryptamine changes the shape of rat blood platelets by combination with a cinanserin-sensitive receptor which is not associated with the active uptake of 5-hydroxytryptamine. Binding of 5-hydroxy[3H]tryptamine to platelets at 4 degrees C demonstrates the presence of three saturable sites, and the highest-affinity site is apparently this 5-hydroxytryptamine receptor.
Blood platelets resemble 5-hydroxytryptamine (5HT) neurons of the central nervous system (CNS) with regard to uptake kinetics of 5HT at the plasma membrane and potencies of 5HT uptake inhibitors at this membrane. Furthermore, by comparing 5HT uptake in normal and reserpinized platelets the site of action of uptake inhibitors (plasma membrane, intracellular amine storage organelles) may be determined. The specific 5HT receptors of platelets whose stimulation induces a reversible shape change of platelets seem to react to drugs in a similar way as 5HT receptors of some CNS-regions such as spinal cord, cortex and possibly reticular formation. In other CNS areas e.g. those with dense 5HT innervation and the hippocampus the 5HT receptors show a reaction to drugs which is partially different from that of the platelet receptors. In other respects e.g. the synthesis and turnover of 5HT platelets do not resemble 5HT neurons. It is concluded that platelets may be used with caution as models for 5HT-neurons with regard to some aspect of 5HT-dynamics.
OBJECTIVE: To compare whole blood platelet aggregation in moderate and severe pre-eclampsia with normal pregnancy. DESIGN: Whole blood platelet aggregation in response to collagen, ADP, PAF, adrenalin and arachidonic acid was measured in the pre-eclampsia group at 36 weeks gestation and at 1, 24 and 48 h and at five days and six weeks post delivery. The normal pregnancy group were studied serially at 12, 20, 28, 32, and 36 weeks gestation and at 1, 24, 48 h and six weeks post delivery. SETTING: Trinity College Medical School, St James's Hospital, Dublin. SUBJECTS: Thirty women with diagnosed pre-eclampsia were recruited for the study. Fifteen of these women had severe pre-eclampsia and the remaining 15 had moderate disease. The pre-eclampsia group were compared with 20 healthy primigravid women with uncomplicated pregnancies and deliveries. RESULTS: In women with severe pre-eclampsia, platelet aggregation in response to collagen, ADP, adrenalin and arachidonic acid was significantly lower at 36 weeks gestation compared with normal pregnancy. Lower levels of collagen induced aggregation were also found at 1 h post delivery when compared with normal pregnancy. Women with moderate pre-eclampsia showed a decreased response to aggregating agents at 36 weeks gestation but this was not significant. ADP, collagen and PAF induced aggregation was higher in women with moderate pre-eclampsia at 36 weeks gestation and during the early puerperium compared with severe pre-eclampsia. CONCLUSIONS: The clinical signs of pre-eclampsia are accompanied by a reduction in platelet responsiveness, the extent of which is related to the severity of the disease. This suggests that an abnormal platelet activation occurs early in pregnancies destined to be complicated by pre-eclampsia. This activation may be involved in the pathogenesis of pre-eclampsia since its inhibition using low dose aspirin has been shown to modify the disease in high risk pregnancies.
OBJECTIVE: To investigate the effects of insulin on the expression of whole-blood platelet membrane P-selectin. METHODS: Flow cytometry (FCM) was used to detect the expression of whole-blood platelet membrane P-selectin, and the effect of insulin on the expression on quiescent and activated plasma platelet observed in normal young subjects. RESULTS: Insulin had no effect on the P-selectin expression on quiescent platelet membrane, but significantly inhibited the up-regulation of P-selectin expression induced by thrombin and collagen respectively, exhibiting dose- and time-dependent effects. CONCLUSION: Insulin can inhibit P-selectin expression on activated platelet membrane.
The synthesis of thromboxane A2 (measured as TXB2) by blood platelets in the presence of ethanol and in platelets from animals dosed chronically with ethanol has been examined. Neither acute nor chronic exposure of guinea pig platelets to ethanol altered thromboxane synthesis. Measurement of total products indicated that neither fatty acid cyclooxygenase nor platelet lipoxygenase was influenced by blood ethanol levels generally associated with intoxication. In human platelets, very high levels of ethanol inhibited thromboxane synthesis in a dose related manner. These results are contrary to reports that high doses of ethanol stimulate arachidonate cyclooxygenation.
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The polarization optical analysis of human blood platelets was carried out by means of topo-optical staining reactions. Similar studies have not been performed so far. With this approach we were able to demonstrate the spatially oriented nature of glycoprotein components in the platelet membrane. Using a sialic acid specific topo-optical reaction the sialic acid component of human platelet membrane was selectively demonstrated and the even distribution of sialic acid residues on the membrane surface was also suggested. Polarization optical analysis has shown a membrane-parallel orientation of oligosaccharide chains carrying sialic acids.
The reference volumes of erythrocytes and blood platelets were evaluated for different age groups of children. The mean volume of cells and the parameters of its distribution, i.e. SD, As and Ex, were found. The mean volume of erythrocytes and the value of positive Ex for the volume of blood platelets were shown to be reliably higher in adults. The investigated blood parameters in children were proven to depend in children on their age and sex. It was concluded that the mentioned peculiarities should be considered in the practice of clinical laboratory examinations.
Blood platelets play an important role in thrombus formation in arteries and on artificial surfaces and in the development of atherosclerosis under hemodynamic conditions of high blood flow. This paper reviews the biological mechanisms implicated in the interactions of blood with vascular and artificial surfaces and, in particular, the role of endothelium injury, platelet activation pathways, the thrombogenic properties of the injured vessel wall and the interactions between blood cells (platelets, monocytes), growth factors and the endothelial and smooth muscle cells of the vessel wall.
Resveratrol (3,4',5-trihydroxystilbene) is a natural molecule with antioxidant action. It is also considered to be a molecule with antiplatelet, anticancer and anti-inflammatory action. The effects of trans-resveratrol on the reactive oxygen species (ROS) generation and thiobarbituric acid-reactive substances (TBARS) in blood platelets induced by endotoxin (lipopolysaccharide, LPS) or thrombin were studied in vitro. The production of superoxide radicals (O2.-) and other reactive oxygen species (H2O2, singlet oxygen, and organic radicals) in the presence of resveratrol was measured by a chemiluminescence method in resting blood platelets and platelets stimulated by LPS (0.3 microg/ 10(8) platelets) or thrombin (2.5 U/10(8) platelets). We have shown that resveratrol (6.25-100 microg/ml) inhibits chemiluminescence and generation of O2.- in blood platelets. It has an inhibitory effect on the production of ROS and TBARS in platelets caused by LPS or thrombin.
Desensitisation of human blood platelets to the effects of 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (1-O-alkylAcGEPC) and palmityl-lysophosphatidate by pre-incubation with these agonists has no effect on the aggregatory or secretory responses to collagen but causes 30-40% inhibition of these responses to thrombin in aspirin-treated platelets. The effects of 1-O-alkylAcGEPC and palmitoyl-lysophosphatidate are not additive. The results are not consistent with the proposal that 1-O-alkylAcGEPC or lysophosphatidate are the mediators for the responses to collagen observed when prostaglandinendoperoxide synthesis is prevented, although they may play some role in the responses to thrombin under these conditions.
Spatial orientation of blood platelets flowing in small arterioles of the rabbit mesentery was investigated using intravital fluorescence microscopy. Only platelets were studied that could be localized objectively within a thin optical section around the median plane of the vessel. The orientation of a platelet was assessed from its microscopic image and described by an angle pair, assuming the platelet to be an ellipsoidal body and using an empirical frequency distribution for its thickness to diameter ratio. The orientation of the platelets was not random; they tended to align themselves with their equatorial planes parallel to the wall. The degree of alignment increased from the center of the vessel toward the wall. As a corollary a frequency distribution of their diameter (3.15 +/- 0.72 micron (mean +/- sd) was obtained in vivo.
The mode of action of protopine on blood platelet aggregation was investigated in the metabolic system of arachidonic acid and in liberation of platelet activating factor using in vitro experimental models. Protopine inhibited the releases of arachidonic acid and platelet activating factor from platelet membrane phospholipids. Protopine also inhibited the conversion of prostaglandin G2 to thromboxane A2, as well as carboxyheptyl imidazole, a thromboxane synthetase inhibitor. These results indicated that protopine functions both as a phospholipase inhibitor and a thromboxane synthetase inhibitor. It is expected that protopine can be applied for treatment of thrombosis as an antiplatelet drug.
The function of blood platelets sampled from the coronary sinus and the superior vena cava was studied in 50 men with coronary artery disease at rest and during pacing-induced angina. At rest, a lower platelet aggregation and retention response was found in coronary sinus compared with vena caval blood. This may be due to refractoriness after previous platelet stimulation or to release of platelet inhibitors in the coronary circulation. During pacing-induced angina, lactate levels indicated that blood was sampled from ischemic myocardium in only 27 of the patients. Pacing-induced angina influenced platelet function differently in blood from ischemic and nonischemic regions. Adenosine diphosphate- and collagen-induced aggregation, platelet retention and plasma beta-thromboglobulin levels remained unchanged in blood from ischemic myocardium during pacing, but increased in blood from nonischemic regions. Thus, factors other than ischemia activated platelets in the coronary circulation during tachycardia-induced stress.
The molecular mechanisms of laser-induced changes in the cell structure and function are not well known. The authors examined the effects of low-power laser irradiation on unnucleated pig blood platelets. The obtained results showed that laser irradiation (1-5 J) caused in blood platelets lipid peroxidation (measured as thiobarbituric acid reactive substances) and superoxide anion generation, concomitant with the release of adenine nucleotides and proteins from platelets. The maximum platelet response to laser irradiation was observed when doses of 1.8-2 J were used. Our results indicate that red laser irradiation induces: (1) platelet secretory process and the release of substances stored in the specific granules (adenine nucleotides, proteins); and (2) lipid peroxidation partly due to stimulation of endogenous arachidonate and production of its metabolites reacting with thiobarbituric acid.