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Biomedical subjects

E Tremoli

Publications and source records attributed to E Tremoli.

At least 109 records · Page 6Linked to original sources
PubMed1986

In vitro effects of aspirin and non steroidal anti-inflammatory drugs on the formation of 12-hydroxyeicosatetraenoic acid by platelets.

The in vitro effects of aspirin and other non steroidal antiinflammatory drugs (NSAIDs) on 12-HETE formation were evaluated in platelet rich plasma (PRP) stimulated with collagen. Aspirin (1 X 10(-4)-1 X 10(-3) M) inhibited 12-HETE production in PRP. Inhibition of 12-HETE formation was detected also in PRP incubated with indomethacin and BW 755C. Sodium salicylate, instead, did not reduce 12-HETE synthesis. Aspirin (3 X 10(-3) M) did not modify 12-HETE synthesis in similarly challenged washed platelet (WP) preparations, inspite of its effect on the cyclooxygenase pathway. It may be concluded that aspirin and other NSAIDs, not only affect the cyclooxygenase pathway, but also inhibit 12-HETE synthesis. In addition it is shown that the 12-HETE synthesis is reduced by plasma and that this effect is enhanced in the presence of aspirin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1986

Controlled evaluation of fat intake in the Mediterranean diet: comparative activities of olive oil and corn oil on plasma lipids and platelets in high-risk patients.

Activities of low-fat diets with olive oil or corn oil on lipids and platelets were studied in 23 middle-aged patients with high atherosclerosis risk for 8 wk. The olive oil diet had a polyunsaturated-saturated ratio of 0.33 vs 1.28 for the corn oil diet. Plasma total cholesterol was reduced with corn oil, but high-density lipoprotein cholesterol levels were lower with corn oil and unchanged or raised by olive. Plasma apolipoprotein B levels were equally reduced by both diets; apolipoprotein AI and the apo AI:B ratio rose only with olive oil. Plasma-glucose levels were lowered significantly with olive oil. Changes in platelet function were characterized by a reduced sensitivity to arachidonic acid (particularly with corn oil) and to collagen (particularly with olive). An olive oil diet with a moderate fat intake (about 30% of total calories) leads to favorable plasma lipoprotein and platelet changes.

Adult↗
PubMed1986

Diets rich in saturated, monounsaturated and polyunsaturated fatty acids differently affect plasma lipids, platelet and arterial wall eicosanoids in rabbits.

New Zealand male rabbits, on a moderate dietary fat intake (10.2% w/w) received, as the major dietary lipid, butter, olive oil and corn oil, respectively, for a period of 8 weeks. At the end of the dietary treatment, plasma total cholesterol was significantly decreased in the corn oil group, compared to butter, whereas the olive-oil-consuming rabbits had an intermediate cholesterolemia; the corn oil and olive oil groups had significantly elevated high-density lipoprotein (HDL) cholesterolemia, compared to the butter group. Maximal platelet aggregability, with collagen and arachidonic acid, did not appear to differ in the three treatment groups. Thromboxane B2 release in the sera of treated rabbits was slightly higher after corn oil administration. The arterial release of prostacyclin (PGI2), tested by perfusing platelet-rich plasma through the aorta of donor rabbits, was lowest in the corn oil group. Corn oil is the most effective dietary fat in reducing cholesterolemia, but it may also reduce PGI2 release from arteries. Butter has the most unfavorable effect on lipidemia and HDL-cholesterol, whereas dietary olive oil shows an intermediate lipid-lowering activity but preserves arterial PGI2 production.

Animals↗
PubMed1986

Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging.

A study in vitro of specimens of human aortic and common carotid arteries was carried out to determine the feasibility of direct measurement (i.e., not from residual lumen) of arterial wall thickness with B mode real-time imaging. Measurements in vivo by the same technique were also obtained from common carotid arteries of 10 young normal male subjects. Aortic samples were classified as class A (relatively normal) or class B (with one or more atherosclerotic plaques). In all class A and 85% of class B arterial samples a characteristic B mode image composed of two parallel echogenic lines separated by a hypoechoic space was found. The distance between the two lines (B mode image of intimal + medial thickness) was measured and correlated with the thickness of different combinations of tunicae evaluated by gross and microscopic examination. On the basis of these findings and the results of dissection experiments on the intima and adventitia we concluded that results of B mode imaging of intimal + medial thickness did not differ significantly from the intimal + medial thickness measured on pathologic examination. With respect to the accuracy of measurements obtained by B mode imaging as compared with pathologic findings, we found an error of less than 20% for measurements in 77% of normal and pathologic aortic walls. In addition, no significant difference was found between B mode-determined intimal + medial thickness in the common carotid arteries evaluated in vitro and that determined by this method in vivo in young subjects, indicating that B mode imaging represents a useful approach for the measurement of intimal + medial thickness of human arteries in vivo.

Adult↗
PubMed1986

Aspirin inhibits platelet 12-hydroxy-eicosatetraenoic acid formation.

The effects of aspirin on platelet 12-hydroxyeicosatetraenoic acid (12-HETE) formation were studied after administration to humans in platelet-rich plasma (PRP) and in vitro in human PRP and in washed platelets (WPs). Healthy volunteers were given orally either single or repeated (1 week) daily doses (20 and 500 mg) of aspirin. Two hours after a single 20 mg aspirin dose, 12-HETE formation by PRP was significantly inhibited. With the highest aspirin dose used (500 mg), the inhibition of 12-HETE formation was more pronounced and long lasting. Thromboxane B2 (TXB2) synthesis was significantly inhibited at 2 hours with the lowest dose. At the 500 mg dose, platelet aggregation was significantly reduced, and TXB2 formation was almost completely suppressed for at least 24 hours. The degree of inhibition of 12-HETE formation at 2 hours after 1 week of daily treatment (20 and 500 mg) was similar to that achieved at 2 hours after the single dose. As far as TXB2 and platelet aggregation are concerned, the effect of 20 mg aspirin was cumulative. In vitro studies show that aspirin (0.25 to 3 mmol/L concentration) significantly inhibits 12-HETE formation in PRP, but not in WPs, suggesting that plasma is required for the aspirin effect on lipoxygenase products. These results indicate that aspirin, even at low doses, not only affects the platelet cyclooxygenase activity but also exerts reversible inhibition of 12-HETE formation, both in vitro and ex vivo. These data may help to further elucidate the role of hydroxyacids in the anti-inflammatory and antipyretic action of aspirin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

Prostacyclin-lipoprotein interactions. Studies on human platelet aggregation and adenylate cyclase.

The in vitro effects of different lipoprotein fractions (VLDL, LDL and HDL) on human washed platelet aggregation, induced by collagen and thrombin, were evaluated in the presence and absence of PGI2. Although VLDL and LDL increased the platelet aggregation while HDL showed an opposite effect, none of the tested lipoprotein fractions affected the potency of PGI2 as inhibitor of platelet aggregation (IC50). In addition, studies were performed to evaluate the effects of lipoproteins on adenylate cyclase activity in human platelet membranes. The three lipoprotein classes inhibited both basal and PGI2-stimulated adenylate cyclase without affecting the EC50 for PGI2. This inhibitory activity was not specifically elicited by any protein or lipid since neither bovine serum albumin nor a lipid emulsion (Intralipid) displayed any inhibition. The effect on adenylate cyclase elicited by VLDL, LDL and HDL does not seem to be correlated with the activity on platelet aggregation. It is concluded that mediators other than cAMP might be involved in the control of platelet function by lipoproteins.

Adenylyl Cyclases↗
PubMed1985

Oral polyunsaturated phosphatidylcholine reduces platelet lipid and cholesterol contents in healthy volunteers.

The effects of orally administered polyunsaturated phosphatidylcholine (PPC) on plasma lipids, lipoproteins and platelet function and composition were studied in seven healthy male volunteers. PPC (Nattermann & Cie, GmbH, Cologne, Federal Republic of Germany), 10 g/day, was given for a 6-week period after a 4-week wash out; laboratory tests were repeated after a further 4-week period after the end of treatment. PPC did not appear, during treatment, to modify the levels of plasma total cholesterol and triglycerides. High density lipoprotein (HDL) cholesterol levels were, however, increased after six weeks of PPC. The most dramatic changes occurred in platelet membrane composition: the total lipid/total protein and the cholesterol/protein ratios were reduced significantly, whereas increases of the phospholipid/total lipid ratio and of the linoleic acid membrane content were observed. Platelet function tests, both in whole blood and in platelet rich plasma, were not modified. Similarly, the thromboxane B2 formation after standard stimuli and the sensitivity to exogenous prostaglandin I2 also were unchanged. During the final wash out period following treatment, a reduction of plasma total and low density lipoprotein (LDL) cholesterol levels also was recorded. PPC appears to be capable of modulating lipid exchanges between cell membranes and the plasma compartment.

Administration, Oral↗
PubMed1985

Plasma lipoproteins affect platelet malondialdehyde and thromboxane B2 production.

Platelet interaction with plasma lipoproteins was studied using gel-filtered platelets free of plasma constituents and purified lipoproteins. On incubation of gel-filtered platelets with plasma lipoproteins at 30 degrees C for 30 min, 100 micrograms of protein/ml of very-low as well as low-density lipoprotein caused 10% increment in platelet aggregation and [14C]serotonin release in parallel to elevation of around 15% of malondialdehyde and thromboxane B2 production. High-density lipoprotein showed the opposite effect and reduced platelet aggregation as well as thromboxane B2 synthesis by 17 and 32%, respectively. Lipoprotein-deficient plasma enhanced platelet function. Preincubation of the platelet suspension with prostacyclin did not prevent the effect of the lipoproteins on the in vitro platelet response as well as on the platelet prostaglandin pathway. Our results suggest that the formation of thromboxane B2 and malondialdehyde is influenced by plasma lipoproteins and that these, in turn, affect platelet aggregation and the release reaction. The possible significance of these results to platelet function in hyperlipidemic patients is discussed.

Blood Platelets↗
PubMed1985

Differential effects of aspirin and indomethacin on platelet and leukocyte thromboxane A2 formation.

In this study, the in vitro inhibitory effects of aspirin and indomethacin on the arachidonic acid induced thromboxane B2 formation by human leukocytes, are evaluated. The results are compared to those obtained using similarly challenged human washed platelets. Acetylsalicylic acid inhibition, calculated as IC50 by a dose-response curve, is more than ten fold higher for leukocytes vs platelets. In fact, a concentration of aspirin as low as 5 microM almost completely suppresses thromboxane B2 formation by washed platelets, whereas a concentration of 50 microM is necessary to achieve the same inhibition with leukocytes. Indomethacin (0.001-100 microM), incubated with platelet and leukocyte suspensions acts similarly to aspirin. Leukocyte and platelet cyclooxygenases are, therefore, differently affected by both aspirin and indomethacin. These differences may be relevant in the understanding of the wide divergence between the aspirin doses used in thrombosis prevention and in the treatment of inflammatory disease.

Aspirin↗
PubMed1985

Pathological significance of the thromboxane-prostacyclin hypothesis.

Disturbances in the balance between the production of thromboxane A2 by the platelets and that of prostacyclin by the vessel wall may play a major role in disease and be a target for therapeutic agents. Acetylsalicylic acid, given in small doses, may inhibit the production of thromboxane A2 without affecting that of prostacyclin. Even if it reduces prostacyclin synthesis, the drug is beneficial as an antithrombotic agent, possibly because it has actions not related to inhibition of cyclooxygenase. Dazoxiben not only inhibits the production of thromboxane A2 by platelets, but also facilitates that of prostanoids, in part by diverting endoperoxides to the blood vessel wall and to leukocytes. Although reduced production of prostacyclin may contribute to the etiology of atherosclerosis, the blood vessel wall of hypercholesterolemic animals exhibits an increased production of prostacyclin. The latter has been given successfully in patients with accelerated turnover of platelets or with peripheral vascular disease. However, its very short t1/2 limits its practical use. The availability of stable prostacyclin derivates, such as ZK 36374, may bypass this problem.

Animals↗
PubMed1985

Control of human and animal platelet aggregation by a new prostacyclin analog.

The in vitro effects of ZK 36 374, a new chemically stable prostacyclin (PGI2) analog, on platelet aggregation were studied and compared to those of PGI2. Significantly lower concentrations of ZK 36 374, versus prostacyclin, were required to inhibit collagen and epinephrine-induced aggregation in human platelet-rich plasma. In contrast, in rat and rabbit platelet rich plasma, PGI2 was more effective than ZK 36 374 in inhibiting the aggregation elicited by ADP and collagen. It is concluded that ZK 36 374 is a potent antiaggregatory compound and may be useful in the prevention of cardiovascular disorders.

Adenosine Diphosphate↗
PubMed1984

Increased platelet sensitivity and thromboxane B2 formation in type-II hyperlipoproteinaemic patients.

Platelet aggregation induced by collagen, ADP and epinephrine, was monitored in 150 type-II patients (115 type IIA and 35 type IIB) and compared with a reference group of normolipidaemic controls; in addition, malondialydehyde formation and thromboxane B2 were examined in a subsample of the type-IIA patients. Threshold aggregatory concentrations were significantly lower in the whole group of type-II patients for all three aggregating agents; no difference in terms of aggregatory response was detected between platelets from type-IIA and -IIB patients. Only 56% of type-II patients, however, exceeded the 95th percentile of the threshold aggregatory concentrations in controls. The formation of malondialdehyde in platelet-rich plasma stimulated with thrombin and collagen, was significantly higher in platelets from type-IIA patients. The production of thromboxane B2 by platelets, from endogenous arachidonic acid in type-IIA patients, was significantly higher and exceeded the highest level found in controls.

Adolescent↗
PubMed1984

Effects of nutrition of disease and life span. II. Vascular disease, serum cholesterol, serum thromboxane, and heart-produced prostacyclin in MRL mice.

Mice of the autoimmune strain MRL/1, the congenic strain MRL/n, and two control strains, Balb/c and C57BL/6 mice, were fed diets which varied in the content of lipid and cholesterol. Serum cholesterol levels were highest in mice fed diets containing cholesterol and lowest in mice fed laboratory "chow." Animals fed diets that increased serum cholesterol had decreased production of prostacyclin by vascular tissue and increased production of thromboxane A2 by platelets. Prostacyclin production by heart tissue in response to arachidonic acid showed a negative correlation (r = -0.86) with serum cholesterol. In contrast, serum thromboxane demonstrated a positive correlation (r = 0.70) with serum cholesterol. The prevalence of autoimmune vasculitis seen in MRL/lpr mice was not affected by diet. However, MRL/lpr mice fed a high-fat, cholesterol-containing diet had intimal vascular lesions containing foam cells typical of arteriosclerosis. It is suggested that diets that raise serum cholesterol may influence the nature of autoimmune-mediated vascular disease by altering the balance between thromboxane and prostacyclin.

Animal Nutritional Physiological Phenomena↗
PubMed1984

Acute effects of ethanol, caffeine, or both on platelet aggregation, thromboxane formation, and plasma-free fatty acids in normal subjects.

The acute effects of ethanol (0.5 ml/kg b.w.) and caffeine (200 mg), alone or in combination, on platelet function and plasma lipid-lipoprotein levels, were tested in four healthy volunteers according to a Latin Square design. The effects of ethanol alone on platelet function (adrenaline- and collagen-induced aggregation, thromboxane B2 formation induced by arachidonic acid) were negligible. Conversely, caffeine significantly reduced maximal aggregation of platelets following adrenaline and collagen, 3 hours after administration; it also significantly increased thromboxane B2 formation 1 hour from administration. The intakes of caffeine and, to some extent, of ethanol at doses in the common daily range, although not profoundly affecting platelet function or lipid parameters, should be given consideration when treatments with platelet-active drugs are prescribed.

Adult↗