The review of contemporary ideas about the influence of flow rate on blood clotting

Normal blood clotting is vitally important for mammals. The diffusion-convection transfer of clotting factors plays a key role in blood clot formation. Since the shear rates of blood flow are very high (up to 7000 s⁻¹), clot formation critically depends on the flow rate. The methods of study of the flow effect on clotting are indirect and the processes are rather complex; therefore, mathematical models of this process are significant for interpretation of results and understanding of the mechanisms. The review expounds the main experimental data on the effect of flow on the blood clotting cascade, some hypotheses and mathematical models explaining different regimes of the functioning of this system. The review is focused on specific problems encountered by researchers in this field. Some of the experimental works have shown that flow decreases the size of the formed fibrin clot and that the dependence of clot formation period on the flow shear rate is a threshold function. However, there are also experimental evidence that the flow can increase production of clotting factors (factor Xa), which must be expressed in the procoagulant action of the flow. Mathematical models of different aspects of clotting give no unified predictions either. Nevertheless, the combined analysis of results of detailed modeling and experiments, in our opinion, may result in understanding of the mechanisms, which determine the behavior of clotting in a flow.     

The stimulation of anthraquinone production by Cinchona ledgeriana cultures with polymeric adsorbents

Summary Anthraquinones produced by suspension cultures of Cinchona ledgeriana are released into the medium, which becomes saturated with products late in the growth cycle. When a high affinity polymeric adsorbent, such as the macro-reticular Amberlite XAD-7, is added to the culture the concentration of anthraquinone in the medium is maintained at a low level and production may be stimulated 15-fold, yielding up to 20 mg/1/day. More than 90% of the product is released from the cells. For maximal yields it is shown that both the amount of adsorbent used and the time after sub-culture at which it is added to the system are critical. The value of such a method for product recovery from immobilised cells is discussed.     

The influence of gamma-irradiation and alimentry factors on prooxidant-antioxidant rat's liver and blood system

The shift of prooxidant-antioxidant balance in side of prooxidants was revealed in rat liver mitochondria and in microsomes and in blood plasma in response to single irradiation (dose 8 Gy). The shift was more expressed in animals with nutrition unbalanced on animal proteins and antioxidant vitamins. In the main it was explained by the initially reduced activity of enzymatic antioxidant system and especially Se-dependent glutathione peroxidase activity. The apply of food addition from Aronia melanocarpa fruits had delayed lipid peroxidation activation in irradiated animals but practically had no effect on activity of enzymatic antioxidant system. The established essential decrease of Se-dependent glutathione peroxidase activity under unbalanced diet is considered the most crucial point in the maintenance of enzymatic antioxidant system reliability in irradiated animals.     

A further insight into the binding of blood clotting factors to membranes

The active site of factor Xa, labelled with dansylglutamylglycylarginine (DnsEGR) is sensitive to association with Ca2+, factor Va and phospholipids. When bound to factor Va, DnsEGR-factor-Xa does not change the composition of the binding site of factor Va, as shown by fluorescence energy-transfer experiments between the Trp residues of factor Va and pyrene-labelled phospholipids. Prothrombin was cleaved by alpha-chymotrypsin into two parts: N-terminal residues 1-41 (peptide 1-41) containing the gamma-carboxyglutamic acid residues (Gla), and des-(1-41)-prothrombin; their membrane association was investigated. Peptide 1-41 contains the aromatic residues Tyr and Trp in positions 24 and 41, respectively, and is suitable for fluorescence spectroscopy. The absence of fluorescence energy transfer between these residues suggests that they are more than 2.8 nm apart. Binding of Ca2+ and of phospholipids involves essentially the Tyr residue, while the C-terminal characteristics of the Trp residue remain unchanged. The conformational change which takes place on binding does not shorten the distance between Tyr and Trp beyond 2.8 nm. Our conclusion is that peptide 1-41 has an extended conformation. This result is compatible with the disordered character of the Gla region found in the crystalline structure of fragment 1 of prothrombin. Ca2+ induces a greater fluorescence energy transfer between prothrombin and membranes labelled with pyrene but has no influence on the binding of des-(1-41)-prothrombin. Moreover, the binding curves of des(1-41)-prothrombin are similar to those of prothrombin in the absence of Ca2+. It is concluded that the Ca2+-independent association of prothrombin with membranes involves essentially that part of the prothrombin molecule deleted in the Gla region.