Steroid transformation

Intravenously administered glucocorticoids , such as prednisone , are the standard of care in acute GvHD [7] and chronic GVHD. [24] The use of these glucocorticoids is designed to suppress the T-cell-mediated immune onslaught on the host tissues; however, in high doses, this immune-suppression raises the risk of infections and cancer relapse. Therefore, it is desirable to taper off the post-transplant high-level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect. [ citation needed ] . Cyclosporine and tacrolimus are inhibitors of calcineurin. Both substances are structurally different but have the same mechanism of action. Cyclosporin binds to the cytosolic protein Peptidyl-prolyl cis-trans isomerase A (known as cyclophilin), while tacrolimus binds to the cytosolic protein Peptidyl-prolyl cis-trans isomerase FKBP12. These complexes inhibit calcineurin, block dephosphorylation of the transcription factor NFAT of activated T-cells and its translocation into the nucleus [25] . Standard prophylaxis involves the use of cyclosporine for six months with methotrexate. Cyclosporin levels should be maintained above 200 ng/ml [26] . Other substances that have been studied for GvHD prophylaxis include, for example: sirolism, pentostatin and alemtuzamab [27] .

The application of immobilized microbial cells has been receiving increasing interest, in particular because of their potential for use in industrial fermentation processes and in analytical procedures. Since the first application of an immobilized microbial biocatalyst for steroid transformation in 1970 by MOSBACH and LARSSON many results have been published concerning the use of such type of biocatalyst in steroid biochemistry and steroid microbiology, respectively. The review deals with the present scientific state of the steroid transformations performed with immobilized biocatalysts, their applications and development trends. In particular the following aspects are discussed: 1(2)-dehydrogenation or hydrogenation, hydroxylation reactions, redox processes in 3,17- and 20-oxogroups, side chain splitting of sterols, 5 alpha-reduction, modification of cholic acid derivatives and the use of immobilized plant cells. The possibility for application of microbial membrane electrodes in steroid analysis has been shown. Up to now, many results of fundamental research are known. There are possibilities for producing expensive steroid derivatives in laboratory apparatus using immobilized biocatalysts. Some of the processes, described here, are of practical interest, and some of them are said to be used industrially, respectively.

Steroid transformation

steroid transformation


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