Anti-F8 (aa 1-216) polyclonal antibody

Objective: Deleterious substitutions of the F8 gene are responsible for causing hemophilia A, which is an inherited bleeding disorder resulting from reduced or absent activity of the coagulant protein factor VIII (FVIII). The most important complication in treatment is inhibitor development toward therapeutic factor VIII. In this study, we aimed to analyze the effects of deleterious substitutions in the F8 gene upon protein structure and function. Materials and Methods: All tests were conducted by computational methods from the CHAMP (CDC Hemophilia A Mutation Project) database. We performed an in silico analysis of deleterious variations using five software programs, Sift, PolyPhen-2, Align-GVGD, KD4v, and MutationTaster, in order to analyze the correlation between variation and the disease. We also studied the correlation between these variations and inhibitor formation. Results: Our analysis showed that these in silico tools are coherent and that there are more variations in the A than the C domains. Moreover, we noticed that there are more deleterious variations than neutral variations in each of the A and C domains. We also found that 13.51% of the patients suffered from a severe form of hemophilia A and that carriers of missense variations developed inhibitors. Also, for the first time, we determined that variation nature is not associated with inhibitor formation. Furthermore, this analysis showed that the risk of developing inhibitors increases when the variation causes a change of amino acid class. Conclusion: This study will help to correctly associate variations with inhibitor development and aid in early characterization of novel variants.

Sustained-release gastroretentive floating matrix tablets of cephradine were prepared for better patient compliance. Eight different tablets were prepared by using two natural polymers, psyllium husk powder (F1-F4) and xanthan gum (F5-F8), through the wet granulation technique. These tablets were characterized by pre- and postcompression analysis, Fourier transform infrared spectroscopy, swelling index study, in vitro buoyancy and dissolution study. Data were analyzed by model-dependent and model-independent analysis to devise the release mechanisms. The polymers exhibited excellent sustained-release behavior as well as binding characteristics. Pre- and postcompression parameters were observed in the specified official pharmacopoeia range. The drug contents of all the formulations were found in the range 95.52-99.63%. No chemical interaction was found between the drug and polymer. All formulations exhibited a good floating time - that is, >24 h - except F8, which remained buoyant for less than 1 h in simulated gastric fluid (pH 1.2). All of the formulations exhibited a direct relation between the swelling index and viscosity of polymer matrices. The significance of the wet granulation technique was indicated by the polymer action as a binding agent in wetting solution. From comparison of the two polymers, psyllium husk powder efficiently retarded the drug release owing to its high gelatinous swollen mass.