Thrombosis synthesis

Courtney M., Jallat S., Tessier L-H., Benavente A., Crystal R.G. Lecocq J-P. (1985) Synthesis in E. coli of alpha,-antitrypsin variants of therapeutic potential for emphysema and thrombosis. Nature, 313, 149-151. 

EHEC all ages/primarily in US, Canada, Europe, South America and Japan 12-60h acute bloody (hemorrhagic colitis in 31— 61%) occasionally nonbloody diarrhea SLT-I and -II - bloodstream - inhibition of protein synthesis - endothelial cell damage - microvascular thrombosis - hemolytic-uremic syndrome... 

Thiazinone, synthesis, 280 Thiazosulfone, 141 Thiethylperazine, 382 Thiobarbital, 275 Thiofuradene, 231 Thiopental, 274 Thiopropazate, 383 Thioridazine, 389 Thiothixene, 400 Thonzylamine, 52 Thrombosis, 397 Thyroid gland, 95 Thyroxine, 95, 97 Tolazamide, 137 Tolazoline, 241 Tolbutamide, 136 Tolycaine, 17... 

Vitamin E is a family of eight compounds, four tocopherols and four tocotrienols. Tocotrienols appear to affect a key enzyme in the liver (HMG CoA reductase), which plays a key role in the synthesis of cholesterol. As such tocotrienols help maintain good cardiovascular health. Vitamin E is an antioxidant and prevents the oxidation of LDL (the bad cholesterol). Vitamin E functions as anticoagulant, which means it delays the clotting of the blood. It can help prevent thrombosis, the formation of blood clots in the arteries. 

Certain structural indications of thromboxane A2 biosynthesis inhibition and hence potential therapeutic utility in arterial thrombosis prompted the synthesis of the pyridine prostanoid 544 (Scheme 165) (83TL3291). Brief metalation of 42 followed by DMF quench afforded aldehyde 541, which upon Homer-Emmons chain extension, reduction, and protection gave 542. Having served as a DMG, the bromo function was subjected to metal-halogen exchange, transmetalation (CuCN), and condensation with an iodo allene to furnish the 3,4-disubstituted pyridine 543. The latter was transformed into two derivatives 544 (with and without double bond), which were shown to be effective inhibitors of thromboxane A2. 

The bis(hydroxycoumarin) derivative dicoumarol (45), which was first identified as the causative agent of sweet clover disease in cattle, is used as an anticoagulant in the treatment of thrombosis. Similar compounds with other linking groups have been used, and warfarin (46), which was first introduced as a rodenticide, is also of value. The hydroxycoumarins interfere with the function of vitamin K in the synthesis of prothrombin and other blood... 

Thrombus Formation. The thromboxanes, especially TXA2, cause platelet aggregations that result in blood clot formation.73 It is unclear whether excessive thrombus formation (as in deep vein thrombosis or coronary artery occlusion) is initiated by abnormal thromboxane production. Certainly, inhibition of thromboxane synthesis will help prevent platelet-induced thrombus formation in individuals who are prone to specific types of excessive blood clotting.84... 

Hyperlipidemia can lead to atherosclerosis and subsequent cardiovascular incidents such as thrombosis and infarction. This condition is often treated by a combination of drug therapy and diet and life-style modifications. Pharmacologic interventions are typically targeted toward decreasing the synthesis of harmful (atherogenic) plasma components, including certain lipoproteins (IDL, LDL, VLDL) that are associated with atherosclerotic plaque formation. 

A new approach to thrombosis therapy using acyl plasmins has been reported by Smith et al.78). Acyl plasmin is catalytically inert and unable to react with plasma inhibitors but still can bind to a fibrin clot. Thus, after the administration, acyl plasmin can circulate without being trapped by the inhibitors and can come into contact with fibrin. Deacylation may then occur to give a fibrin-plasmin complex and this active enzyme is expected to lead to fibrinolysis. The preparation of acyl plasmin of appropriate stability was realized by using the general procedure for the specific synthesis of an acyl enzyme — the inverse substrate method. 

Tada M, Esumi K, Yamageshi M et al. (1984) Reduction of prostaglandin synthesis as a possible cause of transient flow reduction in a partially constricted canine coronary artery. Mol Cell Biol 16 1137-1149 Uchida Y, Yoshimoto N, Murao S (1975) Cyclic fluctuations in coronary blood pressure and flow induced by coronary artery constriction. Jpn Heart J 16 454—464 Warltier DC, Lamping KA, Pelc LR, Gross GJ (1987) A canine model of thrombin-induced coronary artery thrombosis Effects of intracoronary streptokinase on regional myocardial blood flow, contractile function, and infarct size. J Pharmacol Meth 18 305-318... 

Many fruits contain salicylates, which inhihit the synthesis of thromboxane A2, and have an anticoagulant action, in amounts that provide the same intake as the low dose of aspirin used as prophylaxis against thrombosis. 

In summary, all observers do not agree on any single effective dose of aspirin for preventing thrombosis and they do not agree that the same dose of aspirin will work for every indication (62). Since aspirin blocks platelet PG synthesis in every thrombotic disorder in which it is effective and platelets in thrombotic disorders do not differ from normal platelets in their susceptibility to aspirin, then the least amount of aspirin that blocks platelet PG synthesis to a maximal extent is likely to be the most effective and least toxic dose. Such a dose would be 80 mg to 160 mg orally per day. 

It is not clearly understood why in some cases oedema without ascites and in other cases ascites without oedema as well as ascites together with oedema or even pleural effusion without ascites occur. Ascites develops most frequently during the course of liver disease (= hepatogenic ascites), in particular in chronic liver diseases with portal hypertension (= portal ascites), (s. tab. 16.7) Various mechanical, biochemical and neural disorders overlap in their effects and pathways, depending on the underlying liver disease. Only rarely is ascites found in diseases with presinusoidal localization of portal hypertension (such as portal vein thrombosis) or with minor restrictions in the synthesis of albumin (as in biliary cirrhosis). Formation of ascites occurs in about 50% of all cirrhotic patients within 10 years of... 

A causal relation between celecoxib and these thrombotic events cannot be established with certainty on the basis of the available evidence. However, the temporal relation between the start of treatment and the thrombotic event was impressive, at least in three patients, and the findings were consistent with the hypothesis that thrombosis is an adverse consequence of reduced production of systemic prostaglandin I2 brought about by COX-2 inhibition. Reduced synthesis of prostaglandin I2 may act in concert with other thrombotic risk factors (such as those occurring in this series of patients) to precipitate acute vascular occlusion. 

Peniciiiamine Taic and other siiicates Tetradecyisuifate Na Vascular lesion in connective tissue matrix of arterial wall, glomerular immune complex deposits, inhibits synthesis of vascular connective tissue Pulmonary arteriolar thrombosis, emboli Sclerosis of veins Glomerulonephritis... 

Two forms of heparin-induced thrombocytopenia (HIT) have been observed. The first (HIT I) is a transient, mild, and benign thrombocytopenia seen soon after initiation of heparin therapy (normally within 2 days) and is felt to be due to inherent plateletaggregating properties of heparin. A second, more severe form of HIT (HIT II) is typically seen later and is immune-mediated. The incidence of HIT II is estimated at 3-5%. The onset is generally 3-14 days after initiation of heparin therapy but may occur sooner with repeat exposure. HIT II may occur with any dose and type of heparin, but the frequency is highest with continuous intravenous infusions of unfractionated heparin. HIT with subsequent thrombosis is a feared complication. These thrombi can form in the venous or arterial circulation. Thrombotic complications include necrotic skin lesions, myocardial infarction, stroke, and gangrene. Hyperkalemia may be seen with heparin therapy due to aldosterone synthesis inhibition. 

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