1,721,016 research outputs found
REVERSE CHOLESTEROL TRANSPORT - PHYSIOLOGY AND PHARMACOLOGY
No full textReverse cholesterol transport identifies a series of metabolic events resulting in the transport of cholesterol from peripheral tissues to the liver and plays a major role in maintaining cholesterol homeostasis in the body. High density lipoproteins (HDL) are the vehicle of cholesterol in this reverse transport, a function believed to explain the inverse correlation between plasma HDL levels and atherosclerosis. An attempt to stimulate, by the use of drugs, this transport process seems to be of great promise in the prevention and treatment of arterial disease. Only few drugs are now known that can modify the activity of the various factors involved in the process. Clofibrate reduces cholesterol esterification, but the newer fibric acids are generally ineffective as anion-exchange resins. Probucol directly increases the activity and mass of cholesteryl ester transfer protein, thus possibly improving the physiological process of cholesterol removal from tissues. The few available data on the effects of drugs on reverse cholesterol transport should stimulate the search for new agents specifically stimulating this antiatherogenic process
Platelet function in rheumatoid arthritis
No full textPlatelet function tests were evaluated in 20 patients with rheumatoid arthritis (RA), 9 of whom displayed thrombocytosis (greater than 400,000 platelets/microliter). Most patients had an enhanced sensitivity to collagen and epinephrine induced aggregation, as compared with a reference group. In contrast, malondialdehyde (MDA) production, an index of platelet arachidonic acid metabolism, was in the normal range for all the patients except 3, who were LE phenomenon positive. The hypersensitivity of platelets to aggregating stimuli was particularly marked in thrombocytotic patients, who also showed the most striking biochemical and clinical abnormality. These findings indicate the crucial role of platelets in the development and self-sustaining of RA
TGFbeta potentiates TNFalpha –induced tissue factor expression in human endothelial cells
No full textPlatelet aggreation malondialdehyde formation in type IIA hypercholesterolemic patients
No full textPlatelet aggregation induced by threshold concentrations of ADP, adrenaline, collagen and Thrombofax was evaluated in 25 type IIA hypercholesterolemic patients in comparison with 15 control subjects. Malondialdehyde (MDA) formation induced by collagen and thrombin was also studied in a subgroup of 8 patients. In the patient group, irreversible platelet aggregation was induced by significantly lower concentrations of both adrenaline (p is less than 0.05) and Thrombofax (p is less than 0.01). MDA formation induced by both aggregating agents was markedly increased (p is less than 0.01) in type IIA hypercholesterolemic patients
Control of human and animal platelet aggregation by a new prostacyclin analog
No full textThe 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
Effects of PGI2 on platelet aggregation and adenylate cyclase activity in human type IIa hypercholesterolemia
No full textThe sensitivity to PGI2 of platelets of 20 selected type IIa hypercholesterolemic patients was studied and compared to that of platelets of 14 normocholesterolemic subjects. Type IIa subjects required higher concentrations of PGI2 to inhibit platelet aggregation elicited by 1 microM ADP, 1 microgram/ml collagen and 1.4 microM epinephrine. Adenylate cyclase activity was also measured in washed platelet membranes from the two groups of subjects. Adenylate cyclase activity, both basal and PGI2-stimulated, was not statistically different in the two groups examined. Therefore changes at the level of PGI2 receptors coupled to adenylate cyclase are not likely to be responsible for the different platelet sensitivity to prostacyclin
Differential effects of aspirin and indomethacin on platelet and leukocyte thromboxane A2 formation
No full textIn 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
Platelets and arachidonic acid metabolism in human and experimental hypercholesterolemia
No full textThe reported platelet alterations support the concept that platelets may be determining factors in the occurrence of the thromboembolic complications and in the development of atheroclerosis in hypercholesterolemia. Such diseases, however, are multifactorial and platelets may directly or via their released products modulate the behavior of other cell systems, such as leucocytes, endothelial and smooth muscle cells. In particular studies on platelet-vessel wall interactions in different vascular beds, such as coronary and cerebral district, will contribute to the understanding of the basic mechanisms of platelet activation in the atherosclerotic disease
Studies on the antithrombotic action of BOC-D-PHE-PRO-ARG-H (GYKI 14,451)
No full textGyki 14,451, a peptide antagonist of thrombin, was tested on an in vivo model of venous thrombosis in the rat. At the 4 and 6 mg/kg i.v. doses, the compound caused a reduction of over 80% in the incidence of thrombus formation, also markedly reducing thrombus weight. Oral administration of Gyki 14,451 (50 and 50+50 mg/kg) did not induce a significant reduction either of thrombosis incidence or of thrombus weight
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