Plasma proteins aggregates

Hemostasis is the cessation of bleeding from a cut or severed vessel, whereas thrombosis occurs when the endothelium lining blood vessels is damaged or removed (eg, upon rupmre of an atherosclerotic plaque). These processes encompass blood clotting (coagulation) and involve blood vessels, platelet aggregation, and plasma proteins that cause formation or dissolution of platelet aggregates. 

The aggregation and surface properties of Cardax, 3.19, in various aqueous formulations were comprehensively evaluated in 2005 (Foss et al. 2005c), as well as the potential plasma protein binding in mammalian applications with molecular modeling (Zsila et al. 2003). Cardax, 3.19, proved... 

Zsila F, Fitos I, Bikadi Z, Simonyi M, Jackson HL, and Lockwood SF. 2004. In vitro plasma protein binding and aqueous aggregation behavior of astaxanthin dilysinate tetrahydrochloride. Bioorganic Medicinal Chemistry Letters 14(21) 5357-5366. 

Size Exclusion Chromatography (Chapter 31) has also been included as a means of analysis for substances that undergo separation more or less as per their molecular size, viz., insulin and human insulin—for proteins of higher molecular weight corticotrophin—for impurities of higher molecular weights and plasma-protein solution—for polymers and aggregates. 

As a surfactant, ICG exists predominantly in a monomeric form at low concentrations (< 5 pM) but rapidly aggregates at higher concentrations (100 pM) [132]. Although administration of low ICG concentrations is preferred for in vivo applications in order to avoid aggregation, the rapid binding of ICG to plasma proteins prevents intramolecular association in vivo and may favor the use more concentrated ICG samples, if needed. 

The most important reaction in blood clotting is the conversion, catalyzed by thrombin, of the soluble plasma protein fibrinogen (factor 1) into polymeric fibrin, which is deposited as a fibrous network in the primary thrombus. Thrombin (factor 11a) is a serine proteinase (see p. 176) that cleaves small peptides from fibrinogen. This exposes binding sites that spontaneously allow the fibrin molecules to aggregate into polymers. Subsequent covalent cross-linking of fibrin by a transglutaminase (factor Xlll) further stabilizes the thrombus. 

Higher molecular mass dextrans (partieularly dextran 70, 75 and 110) are used to promote short-term expansion of plasma volume thus preventing/treating shoek due to blood loss. A 6% w/v solution of these dextrans exerts an osmotie pressure similar to that of plasma proteins. Generally, an initial dose of 500 ml 1 litre is administered by i.v. infusion. Dextrans also inhibit the aggregation of red blood eells. Thus, they are often used to prevent/treat post-operative thrombo-embolic disorders (see later in this ehapter) and to improve blood flow. 

Mechanism of Action An antiplatelet that directly dilates pulmonary and systemic arterial vascular beds, inhibiting platelet aggregation. Therapeutic Effect Reduces symptoms of pulmonary arterial hypertension associated with exercise. Pharmacokinetics Rapidly, completely absorbed after subcutaneous infusion 91% bound to plasma protein. Metabolized by the liver. Excreted mainly in the urine with a lesser amount eliminated in the feces. Half-life 2-4 hr... 

Cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin, which aggregates to form a blood clot. Thrombin can also bind to cells via the PARI receptor to trigger several other inflammatory responses, such as production of chemokines and nitric oxide. 

---