Effective Increase of Serum Vitamin D3 by IV Application of a Cholecalciferol-N-Acetyl-Galactosamine-Stabilized Dimer: a Clinical Murine Trial Study.

BACKGROUND: Pre-clinical toxicology studies of human Gc-protein (vitamin D binding protein) are of special interest as to the transport of vitamin D and its biological activities. We have demonstrated that the oral application of a special dimeric vitamin D complex reduces oxidative stress and increases the quality of life in autistic children. Therefore, safety and toxic effects of two dimeric cholecalciferol-N-acetyl-galactosamine-albumin complexes were evaluated in increasing intravenous (iv.) vitamin D levels administered in a pre-clinical trial in mice over a 5-week period. METHODS: Over a period of 5 weeks, two times a week, mice received iv. administration of one of the following: (a) 1.2 IE of vitamin D-N-acetyl-galactosamine-albumin (Vitamin D3 NAGA, ImmunoD® group), (b) 1.2 IE of vitamin-D-poly-N-acetyl-galactosamine-albumin (Poly-Nac group), or (c) isotonic saline solution (sham group). Before and after the trial, red and white blood cell panels (RBS, WBC and platelets) were determined. Furthermore, vitamin D levels, electrolytes, and C-reactive protein levels were measured directly before sacrificing. RESULTS: No toxic effects were observed during iv. injection with dimeric vitamin D complexes, neither in the sham group, nor in the two treatment groups. Vitamin D levels increased significantly within 5 weeks in the Poly-Nac group (26.6 ± 8.8 ng/mL; p = 0.001) compared to the sham group (3.1 ± 0.9 ng/mL), and the Poly-Nac group to the ImmunoD group (7.0 ± 3.6 ng/mL; p = 0.003). A significant increase of vitamin D was also obtained in favor of the ImmunoD group compared to the sham (p = 0.03). Electrolytes (K, Na, Cl, Mg, Ca) and C-reactive protein showed no significant differences after administration in all three mice groups. Also, no significant differences were observed between these three groups in the WBC and RBC blood panels. CONCLUSIONS: The two dimeric vitamin D complexes used in this pre-clinical study showed no side or toxic effects after iv. administration in mice, but a sole increase in vitamin D levels without any change in electrolytes or blood cells. Therefore, we assume this newly developed composition to be safe in oral or iv.-administration and further pre-clinical studies can be conducted to evaluate the value in treatment of various diseases related to vitamin D deficiencies.

Prion safety of transfusion plasma and plasma-derivatives typically used for prophylactic treatment.

Reports about transfusion-related transmissions of variant Creutzfeldt-Jakob disease have urged the need for more information regarding the risk for prion contaminated units in the blood supply and the safety of transfusion plasma and biopharmaceuticals derived from this precious raw material. According to a possible epidemiological model, the risk in many European countries is the same or lower than that of human immunodeficiency virus. Comprehensive investigations have shown that the prion safety margin of both single-donor and pooled solvent/detergent treated transfusion plasma is high. Furthermore, prophylactic treatment using plasma-derivatives poses a very low risk in terms of prion disease despite extensive lifetime exposure.