Anti-thrombotic activity

Tab. 12.1 NO donors examined in clinical trials for anti-platelet/anti- thrombotic activity.

Bostwick JS, Kasiewski CJ, Chu V et al. (1996) Anti-thrombotic activity of RG13965, a novel platelet fibrinogen receptor antagonist. Thrombosis Research 82 495-507... 

Epidemiologic studies have indicated a very strong inverse association between HDL-cholesterol levels and the incidence of arteriosclerotic cardiovascular disease [32]. HDL is thought to promote efflux of cholesterol from peripheral cells in the vascular wall and return of that cholesterol to the liver for excretion in bile, a process known as reverse cholesterol transport [21]. HDL has also been shown to have anti-inflammatory and anti-thrombotic activities [21]. Therefore, HDL levels may influence both the hyperlipidemia and inflammatory processes proposed as factors in the development of atherosclerosis. Although clinical data in support of HDL-raising are limited, in the VA-HIT trial gemfibrozil therapy in men with coronary artery disease and low HDL-cholesterol modestly increased HDL levels and reduced coronary events by 22% [33]. Presently, other methods of effectively and safely increasing HDL-cholesterol levels have not been discovered. 

Interactions between GAG chains and various molecules or pathogens play many important biological functions. p-o-Xylopyranosides with a hydrophobic aglycon can penetrate the plasma membrane, initiate the first galactosylation step, and act as an exogenous primer for GAG biosynthesis. Hence, these xylosides have demonstrated interesting biological properties such as anti-thrombotic activity, preservation of human skin properties, and antiproliferative activity. Due to major... 

Satake, T, K. Kamiya, Y. An, T. Oishi Nee Taka, and J. Yamamoto. 2007. The anti-thrombotic active constituents from Centella asiatica. Biol. Pharm. Bull. 30(5) 935-940. 

Certain thioxylosides are good substrates for a glycosyl transferase in vivo, and on oral administration to rats elicit a large increase in plasma concentrations of glycosaminoglycans. The same compounds have important anti-thrombotic activity in rats. 

Antipyretic activity. Ethanol (50%) extract of the plant, administered intraperito-neally to guinea pigs, was inactive " . Anti-thrombotic effect. Olive oil extract of the fmit, administered intragastrically to male rabbits at a dose of 150 g/kg, was active. Lipid profile was improved with decreased platelet hyperactivity and subendot-helial thrombogenicity and less severe morphological lesion of the endothelium and vascular wall . 

This statement strongly advocates for active involvement of pharmacisfs in all phases of medication use. Other standards, such as number 18, which advocates for use of dedicated anti-thrombotic (anti-coagulation) services that facilitate coordinated care management supports those pharmacists who have developed anticoagulation expertise and services. The broad-based support of these standards is a strong statement of the value that pharmacists provide to patients and other members of the health care team. 

Grinnell, B.W., Berg, D.T., Walls, J., and Yan, S.B. (1987). Trans-activated expression of fully gamma-carboxylated recombinant human protein C, an anti thrombotic factor. Bio/Technology 5,1189 1192. 

Summary - Many diverse novel compounds that inhibit different platelet functions show great promise, not only for potential anti-thrombotic agents, but also for more specific effects on prostaglandin and/or thromboxane A2 synthesis, and serotonin or calcium uptake and release. Many active compounds can be used as tools in the search toward a more complete understanding of the physiologic interactions of the hemostatic mechanisms. This better understanding would lead to the development and use of more potent and selective synthetic compounds in the inhibition of platelet aggregation and fibrin formation, and in the enhancement of fibrinolysis for the control of both arterial and venous thrombosis. It is hoped that some of these new compounds will be evaluated clinically in the near fu ture. 

F. 45.6. Anti-thrombotic effects of thrombin. Thrombin, bound to thrombomodulin on the endothehal cell surface, activates protein C. Activated protein C, in complex with protein S, binds to the platelet membrane, and the activated complex destroys Factors Va and Villa, thereby inhibiting the coagulation cascade. 

These serine and cysteine protease cellular pathways are both preferentially targeted by virus-engineered serpins which are now known to block protease activity in the thrombotic/thrombolytic and apoptotic pathways and exhibit amazingly potent anti-inflammatory activities. 

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