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Biomedical subjects

Natalya Ananyeva

Publications and source records attributed to Natalya Ananyeva.

4 recordsLinked to original sources

Treating haemophilia A with recombinant blood factors: a comparison.

The mainstay in the treatment of haemophilia A is replacement therapy with repeated infusions of plasma-derived Factor VIII (FVIII) concentrates or recombinant FVIII products. While modern plasma-derived FVIII concentrates have an excellent safety profile, there is an inexorable shift towards the use of recombinant products, especially in affluent countries. Recombinant FVIII products have demonstrated excellent haemostatic efficacy and higher safety with regard to the transmission of blood-borne pathogens. The experience in haemophilia A treatment with five currently available recombinant FVIII products, including the first third-generation product, Advate, which is completely free from human or animal proteins, is summarised. Some unresolved problems concerning the efficacy and assaying of recombinant factors and future perspectives of both recombinant and plasma-derived FVIII products in global haemophilia care, are also discussed.

Animals↗

Low density lipoproteins interact with acidic fibroblast growth factor and modify its function.

OBJECTIVE: Oxidized LDL (oxLDL) was shown to trigger the release of acidic fibroblast growth factor (FGF-1). Because these components are likely to be present simultaneously in the atherosclerotic milieu, we investigated whether oxLDL interacts with FGF-1 and whether this interaction affects FGF-1 functioning. METHODS AND RESULTS: Using molecular sieve and electrophoretic mobility shift assays, we found that FGF-1 forms a complex with oxLDL in vitro, in contrast to its low affinity for nonatherogenic, native LDL. The FGF-1/oxLDL complex had a dramatically decreased ability to bind heparin and was nonmitogenic on cultured smooth muscle cells. In human atherosclerotic lesions, the highest FGF-1 immunoreactivity was found in macrophages. With respect to oxLDL accumulation, 2 patterns were distinguished: (1) moderate, intracellular in matrix-rich regions containing viable cells and (2) massive, both cell-associated and extracellular oxLDL deposits in foam cell-rich regions with necrotic areas. The proliferating cell nuclear antigen readings for proliferating cells reflected that the mitogenic activity of FGF-1 was confined to the regions where oxLDL was strictly intracellular and was inhibited in the regions with extracellular oxLDL deposition. CONCLUSIONS: oxLDL, besides being a bulky component of the atherosclerotic lesion, possibly manifests its pathogenicity by complexing FGF-1 and inhibiting its growth-promoting function during atherogenesis.

Coronary Artery Disease↗

Development and applications of surface plasmon resonance-based von Willebrand factor-collagen binding assay.

Von Willebrand factor (vWf) functions both as a carrier of factor VIII (fVIII) in plasma and as an adhesive protein providing the primary link between collagen of the extracellular matrix and platelets sequestered from blood flow. The functional activity of vWf correlates with the level of its binding to collagen, which is commonly measured in the enzyme-linked immunosorbent assay (ELISA). We developed an automated collagen-binding assay employing the surface plasmon resonance (SPR) phenomenon, which allows one to quantitatively measure the binding of purified vWf and vWf-containing therapeutic fVIII concentrates to collagen type III immobilized on a biosensor chip. The results of the SPR-based assay highly correlated (r = 0.987) with collagen-binding ELISA. The advantages of the SPR-based assay are its higher accuracy and reproducibility in comparison with ELISA. We applied the developed assay for monitoring structural changes in the vWf component of plasma-derived fVIII/vWf concentrates during a virus inactivation procedure performed by heat treatment. We determined the critical residual moisture content of 2% that can be present in lyophilized concentrates during heat-treatment procedures without causing deteriorative changes in vWf properties. Our data suggest that the SPR-based assay is a useful tool in the development of industrial virus-inactivation procedures, allowing one to preserve vWf activity and achieve the maximal therapeutic efficacy of fVIII/vWf concentrates.

Binding Sites↗