Blood clotting and

Surfaces can be active in inducing blood clotting, and there is much current searching for thromboresistant synthetic materials for use in surgical repair of blood vessels (see Ref. 111). It may be important that a protective protein film be strongly adsorbed [112]. The role of water structure in cell-wall interactions may be quite important as well [113]. 

The importance of quinones with unsaturated side chains in respiratory, photosynthetic, blood-clotting, and oxidative phosphorylation processes has stimulated much research in synthetic methods. The important alkyl- or polyisoprenyltin reagents, eg, (71) or (72), illustrate significant conversions of 2,3-dimethoxy-5-methyl-l,4-ben2oquinone [605-94-7] (73) to 75% (74) [727-81-1] and 94% (75) [4370-61-0] (71—73). 

Coumarin/warfarin, given at a typical dosage of 4 to 5 mg/day, prevents the deleterious formation in the bloodstream of small blood clots and thus reduces the risk of heart attacks and strokes for individuals whose arteries contain sclerotic plaques. Taken in much larger doses, as for example in rodent poisons, Coumarin/warfarin can cause massive hemorrhages and death. 

Other potential adverse effects resulting from liposome administration which need to be studied are undesired complement activation (Cunningham et al., 1979), blood clotting, and pharmacological effects of the lipid components as well as physical obstruction of small capillaries by large particles. 

K Phylloquinone, menaquinones Coenzyme in formation of y-carboxyglutamate in enzymes of blood clotting and bone matrix Impaired blood clotting, hemorrhagic disease... 

Basic aspects of the proteins of the blood coagulation system and of fibrinolysis are described in this chapter. Some fundamental aspects of platelet biology are also presented. Hemorrhagic and thrombotic states can cause serious medical emergencies, and thromboses in the coronary and cerebral arteries are major causes of death in many parts of the world. Rational management of these conditions requires a clear understanding of the bases of blood clotting and fibrinolysis. 

Coagulopathies signal end-stage liver disease. The liver manufactures coagulation factors essential for blood clotting and... 

The first large-scale process to circumvent these limitations was one developed by Genentech, Inc. (South San Francisco, CA) for production of recombinant tissue plasminogen activator (tPA). This protein dissolves blood clots and can be used to treat heart attacks and strokes. This process was developed in the mid-1980s, resulting in final product licensure in 1987. The process required both regulatory and technical breakthroughs. 

It has also been proposed that because of sequence and possible structural homology with the blood clotting factors V and VIII [6] that ceruloplasmin may also participate in blood clotting and its regulation [5]. 

Arachidonic acid (C20 4 n-6) is the precursor for the synthesis of prostaglandin molecules (Section 4.4.4), which have a wide range of biochemical effects on for example, the perception of pain, inflammation, blood clotting and smooth muscle contraction. Docosahexaenoic acid (DHA, C22 6) and eicosapentaenoic acid (EPA, C20 5) are both n-3 long-chain polyunsaturated fatty acids (PUFA) which have been shown to have significantly beneficial effects on intellectual development and inflammatory conditions such as asthma and cardiovascular disease. 

Extracellular peptidases are relatively easy to isolate and are, therefore, well-studied. In higher organisms, they perform a variety of different functions such as food digestion, control of blood pressure and blood clotting, and complement activation, among others. A few examples are compiled in Table 2.2. 

Medicine Ultrasonic imaging (2 -10 MHz) is used, particularly in obstetrics, for observing the foetus and for guiding subcutaneous surgical implements. In physiotherapy lower frequencies (20-50 kHz) are used in the treatment of muscle strains, dissolution of blood clots and cancer treatment. 

Lipoprotein (a) (abbreviated to Lp(a)) is a complex between LDL and apoprotein (a) that forms spontaneously in blood. Lp(a) is secreted by the liver but its function is unknown. A high plasma level of Lp(a) interferes with the conversion of plasminogen to plasmin, the role of which is to break down blood clots and even disperse small clots. 

The serine proteases cleave amide (peptide) bonds in peptides and have a wide variety of functions, including food digestion, blood clotting, and hormone production. They feature as one of the best-understood groups of enzymes as far as mechanism of action is concerned. We are able to ascribe a function to many of the amino acid residues in the active site, and we also understand how they determine the specificity of the various enzymes in the group. 

The absorption of vitamins K2, which are found mainly in cheese, curd cheese, and natto, is much higher and may be almost complete. Thus the nutritional importance of menaquinones is often underestimated. The vitamin K activity is related to the activation of specific proteins involved in blood clotting and bone metabolism. Clinical vitamin deficiency due to dietary inadequacy is rare or nonexistent in healthy adults, thanks to the widespread distribution of the vitamin K in foodstuffs and the microbiological flora of the gut, which synthesizes menaquinones. Only infants up to 6 months are at risk of bleeding due to a vitamin K deficiency. No data on negative effects of an overdose of vitamin K are found [417]. 

Fibrin—Blood protein involved in blood clotting and wound healing. 

A significant body of evidence suggests that the calcium channel blockers may interfere with platelet aggregation in vitro and prevent or attenuate the development of atheromatous lesions in animals. Clinical studies have not established their role in human blood clotting and atherosclerosis. 

The anticoagulant heparin is a polysaccharide sulfate which can form an electrostatic complex with blood-clotting factors (see ASIDE on blood clotting) and prevent the cascade from progressing. 

The physiological role of vitamin K is in blood clotting and is essential for the synthesis of at least four of the proteins (including prothrombin) involved in this process. Vitamin K also plays a role in the synthesis of a protein (osteocalcin) in bone. Vitamin K deficiency is rare but can result from impaired absorption of fat. Vitamin K levels in the body are also reduced if the intestinal flora is killed (e.g. by antibiotics). Vitamin K toxicity is rare but can be caused by excessive intake of vitamin K supplements. Symptoms include erythrocyte haemolysis, jaundice, brain damage and reduced effectiveness of anticoagulants. 

TEicosanoids are paracrine hormones, substances that act only on cells near the point of hormone synthesis instead of being transported in the blood to act on cells in other tissues or organs. These fatty acid derivatives have a variety of dramatic effects on vertebrate tissues. They are known to be involved in reproductive function in the inflammation, fever, and pain associated with injury or disease in the formation of blood clots and the regulation of blood pressure in gastric acid secretion and in a variety of other processes important in human health or disease. 

The thromboxanes have a six-membered ring containing an ether. They are produced by platelets (also called thrombocytes) and act in the formation of blood clots and the reduction of blood flow to the site of a clot. The nonsteroidal antiinflammatory drugs (NSAIDs)— aspirin, ibuprofen, and meclofenamate, for example— were shown by John Vane to inhibit the enzyme prostaglandin H2 synthase (also called cyclooxygenase or COX), which catalyzes an early step in the pathway from arachidonate to prostaglandins and thromboxanes (Fig. 10-18 see also Box 21-2). 

Vermeer, C. (1990) y-Carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem. J. 266, 625-636. Describes the biochemical basis for the requirement of vitamin K in blood clotting and the importance of carboxylation in the synthesis of the blood-clotting protein thrombin. 

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