Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of aspirin, nifedipine, dipyridamole and cavinton on platelet aggregability in patients with atherosclerosis has been studied using various agents to induce aggregation. The drugs reduced platelet aggregability when aggregation was induced by ADP, adrenaline, or collagen alone. However, if platelet aggregation were induced by combinations of the agonists (including combinations of ADP with either adrenaline or platelet-activating factor (PAF), adrenaline with PAF, and collagen with ADP), the anti-aggregant effects of aspirin, dipyridamole, and cavinton were significantly reduced. The effect of nifedipine was less markedly reduced, especially by combinations which included adrenaline. The data suggest that positive agonist interactions may lead to a reduction in the therapeutic activity of antiplatelet drugs.
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PMID:Effects of aspirin, dipyridamole, nifedipine and cavinton which act on platelet aggregation induced by different aggregating agents alone and in combination. 157 42

Dialysis patients have an inordinate risk of cardiovascular events. Fish oils, rich in n-3 fatty acids, are believed to be beneficial in the prevention of atherosclerosis and thrombosis. Hence, the use of fish oils deserves consideration as a preventative or therapeutic intervention in dialysis patients. The suggestion has been made that n-3 fatty acids could increase the risk of bleeding, and thus, the safety of the use of these agents in dialysis patients must be established before long-term studies are undertaken. This study addresses the effect of n-3 fatty acids on the hemostatic profile of dialysis patients. Sixteen patients on chronic dialysis therapy were randomized to fish oil (MaxEPA) or placebo (olive oil) in a double-blind cross-over study. They received 3.6 g of n-3 fatty acids for 4 wk. Bleeding times were 4.8 +/- 0.4 min on MaxEPA and 4.5 +/- 0.3 min on placebo. Platelet aggregation to low-dose ADP or collagen also remained unchanged. There was a trend to lower serum triglyceride levels (2.7 +/- 0.5 versus 3.4 +/- 0.6 mmol/L, fish oil versus placebo) that did not reach statistical significance. Gastrointestinal side effects occurred in 10 of the 16 subjects and were severe in 5 patients. These side effects occurred in both the olive oil and the fish oil groups. The study had a 95% chance of detecting a clinically doubling significant increase in bleeding time, i.e., beta error less than 5%. In conclusion, n-3 fatty acids do not introduce a clinically important risk of bleeding for patients with end-stage renal disease.
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PMID:Effect of n-3 fatty acids from fish oil on hemostasis, blood pressure, and lipid profile of dialysis patients. 161 Sep 84

In a double blind, randomized trial, the effects of aspirin (1, 5, and 15 mg/kg) were compared with the changes in platelet aggregation at 6 and 24 hours after dosage. It is found that there is a negative correlation between aspirin hydrolysis velocity in blood and capability of aspirin to decrease platelet aggregation with ADP and collagen in patients with atherosclerosis. Relationship between these parameters depends on aspirin dosage. The correlation was more marked for low doses of aspirin. It is suggested that the effect of aspirin in low dosage on platelet aggregation might be ineffective in many patients without control of aspirin hydrolysis velocity in blood.
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PMID:Dose-dependent aspirin hydrolysis and platelet aggregation in patients with atherosclerosis. 161 22

Clopidogrel is a new thieno-pyridine derivative and has a more potent inhibitory effect on platelet aggregation, dependent on ADP rather than ticlopidine. In a phase I study performed in Japan, significant inhibition of ADP-induced platelet aggregation and prolongation of bleeding time was observed in the dose range of 25, 50 and 75 mg. These effects were comparable to 200 or 300 mg of ticlopidine. Antithrombotic effects have also been shown in experimental animal models. Clopidogrel is expected to reduce the incidence of neutropenia since smaller doses are sufficient to suppress platelet aggregation compared to ticlopidine. Clopidogrel has been proven to be a potent and well-tolerated antiplatelet agent for atherosclerosis patients at risk of thrombosis, in Europe.
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PMID:[Antiplatelet effect of clopidogrel]. 161 93

The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p less than 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radiolabelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha-granule content liberation (beta-thromboglobulin: p less than 0.01; PDGF: p less than 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications.
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PMID:Ticlopidine and platelet function in healthy volunteers. 161 96

Twenty patients with obliterative atherosclerosis in the lower extremities arteries (Fontaine's stage II) were treated with nitrendipine (Bayotensin) given in the dose of 20 mg daily for 6 weeks. This therapy with nitrendipine produced improvement manifested by the prolongation of the distance of intermittent claudication, shortening of pain duration, increase in blood flow in the ischemic extremity, and increase in pressure index. At the same time, nitrendipine decreased ADP-produced platelet aggregation and activated fibrinolytic system. Clinical trials have shown that nitrendipine is effective in the obliterative atherosclerosis in the lower extremities.
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PMID:[Use of nitrendipine in treating patients with obliterative atherosclerosis of arteries in the lower extremities]. 166 21

The endothelial cells can release both relaxing and contracting substances. The former include prostacyclin and endothelium-derived relaxing factor (EDRF, which most likely is nitric oxide, or a nitrosoderivative releasing nitric oxide, derived from L-arginine). Candidates as endothelium-derived contracting factors (EDCF) include superoxide anions thromboxane A2 and the peptide endothelin. Endothelium-derived relaxing factor causes relaxation of vascular smooth muscle by activation of the soluble form of guanylate cyclase which leads to an accumulation of cyclic GMP; it also reduces platelet adhesion and aggregation. The latter effect is synergistic with the inhibition evoked by prostacyclin. The release of EDRF and prostacyclin plays a key role in the protective role of the endothelium against vasospasm and the unwanted coagulation of blood. Indeed, thrombin and aggregating platelets are potent stimuli for the release of EDRF. The platelet-products responsible are the adenine nucleotides, ADP and ATP, which activate P2y-purinergic receptors on the endothelial cells and 5-hydroxytryptamine (serotonin) that stimulates 5-HT1-like serotonergic receptors. The response to serotonin, but not that to the adenine nucleotides, is mediated by a pertussis toxin-sensitive mechanism. When endothelial cells regenerate, or are cultured, they selectively lose the pertussis toxin-sensitive mechanism of release, which results in a marked decrease in sensitivity to exogenous and platelet-released serotonin. As a consequence, the endothelial cells exhibit a considerably reduced response to aggregating platelets. This phenomenon, which can be exacerbated by hypercholesterolemia, favors ongoing platelet aggregation and vasospasm, and constitutes a first step toward atherosclerosis.
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PMID:Platelet-derived serotonin, the endothelium, and cardiovascular disease. 171 75

Platelets are involved in the progressive pathogenesis of atherosclerosis. It has been shown that there is usually an increase in platelet aggregation between 6 and 9 a.m.; in the present study. in 10 patients suffering from chronic occlusive arterial disease, the impedancemetric method was used to evaluate, in whole blood, platelet aggregation induced by ADP and collagen the day prior to and the day following the evening administration of 300 mg picotamide. Analysis of the data obtained shows, in accordance with the findings of other authors, in increase of platelet aggregation from 6 a.m. to 9 a.m. This increase is suppressed by the evening administration of the anti-aggregant.
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PMID:[Changes in morning platelet aggregation in patients with peripheral obliterating arteriopathy after evening administration of picotamide]. 182 69

The effects of the intravenous administration of 100 mg of trapidil on systolic and diastolic left ventricular functions and coronary sinus blood flow, as well as on myocardial lactate metabolism and platelet aggregation, were investigated before and after pacing in 12 patients with coronary artery disease. Pacing without administration of trapidil provoked angina in 6 of these patients. During rest, trapidil decreased the mean blood pressure by an average of 5 mmHg (from 112 +/- 15 to 107 +/- 8 mmHg, p less than 0.05) and the left ventricular end-diastolic pressure by an average of 4 mmHg (from 10 +/- 3 to 6 +/- 2 mmHg, p less than 0.05). Trapidil also caused both the max dp/dt and the coronary sinus blood flow to increase slightly, although it had no significant effect on diastolic function, myocardial lactate metabolism, or platelet aggregation. During the pacing that followed trapidil administration, chest pain was not provoked in the same 6 patients who had previously experienced chest pain on pacing. The extent of ST-segment depression also improved from -1.6 +/- 0.3 to -0.9 +/- 0.7 mm (p less than 0.05) and there was a significant suppression of the production of myocardial lactate. When pacing was terminated, trapidil caused a decrease in left ventricular systolic pressure from 173 to 156 mmHg (p less than 0.05), and also caused a decrease of the left ventricular end-diastolic pressure, from 16 +/- 4 to 8 +/- 2 mmHg (p less than 0.05). Trapidil had no significant effect on platelet aggregation activity with either a 1 microM or a 2 microM dose of ADP (adenosine diphosphate). However, the beta-TG level was suppressed, decreasing from 119 +/- 14 to 99 +/- 19 ng/ml in the arterial blood (p less than 0.1) and from 114 +/- 9 to 103 +/- 17 ng/ml (p less than 0.1) in the coronary sinus blood. Reductions in the preload and afterload by trapidil were of far greater magnitude than either its coronary dilatory or positive chronotropic effects in patients with coronary artery disease. Thus trapidil, a new antianginal agent appears to inhibit the production of platelet derived growth factors and may, therefore, protect the arteries from atherosclerosis as it promotes beneficial systemic hemodynamics in patients with depressed ventricular function.
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PMID:The effects of trapidil on left ventricular function and platelet aggregation in patients with coronary artery disease subjected to pacing. 183 67

There is considerable evidence from previous studies that platelets play an important role in the development and progression of atherosclerosis in hypertension, more so in relation to the stage of hypertension. Seventy one hypertensive patients (WHO stage I: 39, stage II: 23, stage III: 9) aged 19-84 (mean age: 56, 59 and 62 respectively for each stage) and 37 normal controls (aged 22-72 with a mean age of 52) were involved in this study. Hematocrit, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), beta-TG/PF4 ratio, total cholesterol (TC), low density lipoprotein-C, and triglycerides were higher in the hypertensive group while platelet count, circulating platelet aggregates, and high density lipoprotein-C were higher in the normotensive group. Among the hypertensives, stage III patients showed the highest beta-TG, PF4, beta-TG/PF4 ratio, triglycerides, and stage I with the least elevation. There were no significant differences noted in the ADP or epinephrine-induced platelet aggregation in both the normal and hypertensive patients. Other parameters such as heart rate, serum sodium, potassium, renal and liver function tests, plasma renin activity, aldosterone, fibrinogen thromboxane B2 and 6-Keto-PGF1 alpha, showed no significant differences in both groups. This study clearly showed that beta-TG/PF4 ratio and triglycerides are closely related to the stage of hypertension and are good indicators of in vivo platelet activation in hypertensives which may account for the acceleration of hypertensive vascular complications secondary to atherogenesis.
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PMID:Relationship of platelet specific proteins and other factors to atherosclerosis in various stages of hypertension. 183 85


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