1,720,980 research outputs found
Oxidized Lipids and platelet activation: interaction with Nitric Oxide
No full textOxidized low density lipoprteins (LDL) and products of lipid peroxidation such as F2-isoprostanes are weak platelet agonists. Ox-LDL and F2-isoprostanes are able to prevent in vitro the antiaggregatory effects of endothelial cells releasing NO or NO-donor
Decrease of platelet intracellular pH and adhesion by ticlopidine in patients with vascular disease
No full textBACKGROUND: Ticlopidine inhibits platelet aggregation by preventing the binding of fibrinogen to its platelet receptor. We examined whether this inhibition involved platelet transduction system such as Na+/H+ pump and platelet intracellular calcium. METHODS: Platelet adhesion in 13 patients with peripheral vascular disease treated with ticlopidine, 250 mg b.i.d for 30 days, was measured in culture microplates before and after therapy. The microplate wells were coated with human plasma, fibrinogen or collagen, and platelet adhesion was studied in the resting condition and after stimulation with 1 and 10 microM ADP. At the same time, platelet intracellular calcium and ADP-induced calcium increases were measured with the fluorescent indicator Fura 2. In addition, intracellular pH and thrombin-induced pH variations were measured with the fluorescent probe BCECF. RESULTS: Platelet adhesion to plasma and fibrinogen was significantly reduced (about 50%) after treatment with ticlopidine, while adhesion to collagen was not modified. Basal calcium and ADP-induced calcium increase were not significantly different before and after ticlopidine. Platelet basal intracellular pH was reduced (from 7.44+/-0.009 to 7.41+/-0.017, p<0.05), but agonist-induced alkalinisation was not significantly different. Early acidification, not dependent on Na+/H+ exchange, was also reduced (p<0.05). CONCLUSIONS: These data do not seem to support the hypothesis that ticlopidine-induced reduction of platelet adhesion depends on alteration of the mechanisms determining signal transduction, at least as far as basal and post-stimulation intracellular calcium is concerned. On the contrary, the possibility that ticlopidine inhibits the Na+/H+ antiport remains open to consideration
In vitro study of antiaggregating activity of two nitroderivative of acetylsalicylic acid.
No full textThe antiplatelet activity of two new nitrocompounds, chemically related to acetylsalicylic acid (NCX 4215 and NCX 4016), was studied in vitro to verify the hypothetical dual action of these drugs. Both drugs, in a dose-dependent way, inhibited arachidonic acid-induced platelet aggregation and thromboxane A2 production, measured as thromboxane B2 concentration in whole blood. These effects are likely to be related to cyclo-oxygenase inhibition. NCX 4215 and NCX 4016 in a dose-dependent way inhibited also thrombin-induced aggregation of platelets pretreated with acetylsalicylic acid. These inhibitory effects are related to nitric oxide release and cGMP increase and significantly reversed by oxyhaemoglobin and methylene blue. Either as a cyclo-oxygenase inhibitor or as a nitric oxide donor, NCX 4016 proved to be significantly more potent than NCX 4215
Oxidized low density lipoprotein (LDL) and platelet intracellular calcium: Interaction with nitric oxide
No full textThe present study tested the effects of ox-low density lipoprotein (LDL) on nitric oxide (NO)-dependent decrease in agonist-stimulated [Casup 2sup +](i). The effects of ox-LDL on platelet aggregation were also evaluated. Platelets loaded with FURA 2 AM (2 mumol/litre) were incubated with NO-donors for 2-10 min to obtain a 40-50% reduction in [Casup 2sup +](i) and with NO-donors plus ox-LDL (100 mug of protein/ml). Thrombin (0.03 U/ml) was used as an agonist. In some experiments 8-Br-cGMP (0.5-1 mmol/l) was used to investigate the NO-dependent intraplatelet signalling system. Slightly oxidized LDL was obtained by leaving native LDL in the light at room temperature for at least 7 days. Ox-LDL did not cause any increase in thrombin-induced [Casup 2sup +](i) (control: 215.4 +/- 44.3 nmol/l, ox-LDL 223.4 +/- 35.3 nmol/l, M +/- SEM; n = 8) and platelet aggregation (control: 78.7 +/- 4.9%, ox-LDL: 78.9 +/- 4.2%, n = 12). Ox-LDL antagonized the effects of NO-donors on platelet [Casup 2sup +](i) (NO-donor: 137.4 +/- 22.1 nmol/l, NO + ox-LDL: 177.3 +/- 27.6 nmol/l, n = 11; P < 0.001) and platelet aggregation (NO-donor: 15.4 +/- 3.4%, NO + ox-LDL: 28.9 +/- 3.8%, n = 24; P < 0.001). Ox-LDL did not affect the inhibitory activities of 8-Br-cGMP on platelet aggregation (8-Br-cGMP: 22.0 +/- 8.5%, 8-Br-cGMP + ox-LDL: 19.3 +/- 7.8%, n = 5) and platelet [Casup 2sup +](i). In conclusion, slightly oxidized LDL does not directly activate platelets and does not affect the intracellular NO-dependent signalling system. The present results suggest that LDL reduces the antiplatelet activity of NO mainly by preventing its biological effects
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Venous stasis and whole blood platelet aggregometry: a question of data reliability and patient safety
No full textThe assessment of platelet function by multiple electrode aggregometry (MEA) (Multiplate, Roche Diagnostics GmbH) is common in laboratory hematology. As regards the ISO 15189:2012 international standard, appropriate use of laboratory equipment requires appropriate pre-examination activities (e.g., blood collection). Venous stasis can influence several blood analytes, but the tourniquet time is rarely regarded as a source of variability. Aim of the present study was to evaluate the impact of venous stasis on platelet function by MEA. A total of 6 ml of blood was collected from 20 volunteers into two 3.0 ml Hirudin vacuum tube (Roche Diagnostics GmbH), and subjected to two procedures: procedure 1 (no stasis) - collection after localization of forearm vein by subcutaneous tissue transilluminator device without tourniquet; procedure 2 (stasis) - collection after localization of vein by prior 60 s tourniquet application. Samples were processed on Multiplate, for: ADP-test (without prostaglandin E1), ADP HS-test (with prostaglandin E1), ASPI-test, COL-test, RISTO H-test (high concentration, 0.77 mg/ml), RISTO L-test (low concentration, 0.20 mg/ml), and TRAP-test. The significance of the differences between samples was assessed by Wilcoxon ranked-pairs test. Surprisingly, the results of ADP HS-test, ASPI-test, COL-test, and RISTO H-test appeared unbiased by venous stasis. RISTO L-test, ADP-test, and TRAP-test were significantly biased; the mean percent difference between stasis and no stasis were -7.2% (P = 0.040), -28.4% (P = 0.015), and 1.1% (P = 0.031), respectively. In conclusion, the tourniquet should be avoided when assessing platelet function by MEA
Oxidized LDL and intracellular calcium: interaction with nitric oxide.
No full textThe present study tested the effects of ox-low density lipoprotein (LDL) on nitric oxide (NO)-dependent decrease in agonist-stimulated [Ca2+]i. The effects of ox-LDL on platelet aggregation were also evaluated. Platelets loaded with FURA 2 AM (2 micromol/litre) were incubated with NO-donors for 2-10 min to obtain a 40-50% reduction in \[Ca2+]i and with NO-donors plus ox-LDL (100 microg of protein/ml). Thrombin (0.03 U/ml) was used as an agonist. In some experiments 8-Br-cGMP (0.5-1 mmol/l) was used to investigate the NO-dependent intraplatelet signalling system. Slightly oxidized LDL was obtained by leaving native LDL in the light at room temperature for at least 7 days. Ox-LDL did not cause any increase in thrombin-induced [Ca2+] (control: 215.4 +/- 44.3 nmol/l, ox-LDL 223.4 +/- 35.3 nmol/l, M +/- SEM; n = 8) and platelet aggregation (control: 78.7 +/- 4.9% , ox-LDL: 78.9 +/- 4.2% , n = 12). Ox-LDL antagonized the effects of NO-donors on platelet [Ca2+]i (NO-donor: 137.4 +/- 22.1 nmol/l, NO + ox-LDL: 177.3 +/- 27.6 nmol/l, n = 11; P < 0.001) and platelet aggregation (NO-donor: 15.4 +/- 3.4% , NO + ox-LDL: 28.9 +/- 3.8%, n = 24; P < 0.001). Ox-LDL did not affect the inhibitory activities of 8-Br-cGMP on platelet aggregation (8-Br-cGMP: 22.0 +/- 8.5%, 8-Br-cGMP + ox-LDL: 19.3 +/- 7.8%, n = 5) and platelet [Ca2+]i . In conclusion, slightly oxidized LDL does not directly activate platelets and does not i affect the intracellular NO-dependent signalling system. The present results suggest that LDL reduces the antiplatelet activity of NO mainly by preventing its biological effects
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