Human factors xiii

Kreilgaard, L, Frokjaer, S., Flink, J.M., Randolph, T.W., Carpenter, J.F. Effects of additives on the stability of recombinant human factor XIII during freeze-drying and storage in the dried solid. Arch. Biochem. Biophys. 360,121-134,... 

As the basis for decisions about the first dosing in humans, the preclinical safety program needs to mimic the intended clinical regimen. Although these studies are commonly conducted in normal healthy animals, they may also require development and use of an animal model that mimics the health status or condition if it is deemed to possibly sensitize the subject to treatment. For example, we have conducted studies evaluating the safety of recombinant human Factor XIII in an animal model of extracorporeal blood circulation [6] and the safety of recombinant human thrombin in an animal model of hepatic resection [7]. 

Ponce R, Armstrong K, Andrews K, Hensler J, Waggie K, Heffernan J, Reynolds T, Rogge M. Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation. Toxicol Pathol 2005 33(6) 702-10. 

Ponce RA, Visich JE, Heffernan JK, Lewis KB, Pederson S, Lebel E, Andrews-Jones L, Elliott G, Palmer TE, Rogge MC. Preclinical safety and pharmacokinetics of recombinant human factor XIII. Toxicol Pathol 2005 33(4) 495-506. 

Kreilgaard, L. Jones, L.S. Randolph, T.W. Erokjaer, S. Elink, J.M. Manning, M.C. Carpenter, J.E. Effect of Tween 20 on freeze-thawing- and agitation-induced aggregation of recombinant human factor XIII. J. Pharm. Sci. 1998, S7(12), 1597-1603. 

Recombinant human factor XIII Trehalose and sucrose preserved the native dimeric structure of the protein and prevented aggregates formation [32]... 

Lorand, L., Losow sky, M.S. and Miloszewski, K. (1980) Human Factor XIII Fibrin stabilizing factor. In Progress in Hemostasis and Thrombosis (I. H. Spaet, ed.), pp. 245-290, Grune and Stratton, New York. 

A (very rare) genetic deficiency in the production of factor XIII also results in impaired clotting efficacy in affected persons. In this case, covalent links that normally characterize transformation of a soft clot into a hard clot are not formed. Factor XIII preparations, partially purified from human blood, are used to treat individuals with this condition to date, no recombinant version of the product has been commercialized. 

Gao, J., Hooker. B.S., and Anderson, D.B. (2004). Expression of functional human coagnlation factor XIII A-domain in plant cell snspension s and whole plants. Protein Exp. Purif. 37(1) 89-96. 

Moaddel, M., Farrell, D. H., Daugherty, M. A., and Fried, M. G. (2000b). Interactions of human fibrinogens with factor XIII Roles of calcium and the gamma peptide. Biochem. 39, 6698-6705. 

For liquid formulations, shaking the formulation increases the air/liquid interface in the formulation and often leads to protein denaturation. Several proteins are susceptible to denaturation by shaking, including human growth hormone (hGH) and recombinant factor XIII, both of which formed insoluble aggregates after shaking. 

Radek, J. T. Jeong, J. M. Wilson, J. Lorand, L. Association of the A Subunits of Recombinant Placental Factor XIII with the Native Carrier B Subunits from Human Plasma. Biochemistry, 1993, 32, 3521. 

Factor XIII is found in plasma, platelets, and placenta. The human plasma factor XIII has a molecular weight of 320,000 and is composed of two subunits with molecular weights of 75,000 (a) and 88,000 (JS). The platelet factor has a molecular weight of 146,000 and a single type of subunit with a molecular weight of 75,000. The a subunit of the plasma factor seems to be identical to that of the platelets, a and j8 subunits can be combined to reconstitute the entire molecule. Proteolytic activation of factor XIII is associated with a loss in molecular weight of about 4,000. The polypeptide contains an N-acetylserine for N terminal and the amino acid sequence of the bovine and the human peptide has been determined [49]. 

Biocoll pooled donor plasma fibrinogen (>75 mg/riiL) Factor XIII (<10 U/mL) ])lasminogeii (31 mg/niL) aprotinin (30 ing/mL) human thrombin (>500 U/mL) solvent detergent I realment of thrombin Sc fibrinogen nanofiltration of thrombin Centre de Transit is ion Sa ngui n e I ille, F ram e... 

Bolheal pooled donor plasma fibrinogen (80 mg/iiiL) Factor XIII (75 U/mL) plasminogen (detectable) aprotinin (1000 KIU/mL) human thrombin (250 LT/mL) pasteurization (65 C) fibrinogen (144 h) Sc. thrombin (96 h) Kaketsu-k n 668 Okubo Shimizu Kumamoto 860 Japan... 

MelGlii [)ooled donor plasma fibrinogen ( 75 mg/niL) Factor XIII (<10 U/iiiL) plasminogen (trace) human thrombin (200 U/mL) solvi Ut detergent andUVC Melville Biologies Melville New York USA... 

---