Cyclosporine cell culture

Trifillis, A., Regec, A., Hallcraggs, M. and Trump, B. (1984). Effects of cyclosporine on cultured human renal tubular cells. Human Toxicology 3 454. 

Rodriguez-Puyol D, Lamas S, Ollvera A, Lopez-Farre A, Ortega G, Hernando L,and Lopez-Novoa JM. Actlonsof cyclosporin Aon cultured rat mesangial cells. Kidney Int 35 632-637,1989. 

Tiemann C, Prohaska W, Korfer R, Korner M, Brinkmann T, Kleesiek K. Effect of cyclosporine A on the release of tissue factor pathway inhibitor from endothelial cells in heart transplant patients and cell culture. Eur J Clin Chem Clin Biochem 1997 35 661 -667. 

RezzanI R, Angoscini P, Borsani E, Rodella L, Blanch R. Cyclosporine A-induced toxicity in two renal cell culture models (EEC-PKl and MDCK). Histochem J 2002 34 27-33. 

Esposito C, Fornoni A, Cornacchia F, Bellotti N, Fasoli G, Foschi A, Mazzucchelli I, MazzulloT, Semeraro L, Dal Canton A. Cyclosporine induces different responses in human epithelial, endothelial and fibroblast cell cultures. Kidney Int 2000 58 123-130. Duymelinck C, Deng JT, Dauwe SE, De Broe ME, Verpooten GA. Inhibition ofthe matrix metalloproteinase system in a rat model of chronic cyclosporine nephropathy. Kidney Int 1998 54 804-818. 

Walker RJ, Lazzaro VA, Duggin GG, Florvath JS, Tiller DJ. Synergistic toxicity of cyclosporin A and streptomycin in renal epithelial cell cultures. Res Commun Chem Pathol Pharmacol 1988 62 447-460. 

Blaehr FI, Andersen CB, Ladefoged J. Acute effects of FK506 and cyclosporine Aon cultured human proximal tubular cells. Eur J Pharmacol 1993 228 283-288. 

In this context, the applications of PyMS in biotechnology are of particular interest. The technique has been used to detect and measure the level of metabolites produced in cell culture, such as indole produced by cultured Escherichia coli cells grown in different types of media, and to predict the yield of recombinant protein in culture systems, such as E. coli producing recombinant cytochrome B5 or a-interferon. An analogous application is the use of PyMS to profile drugs and their metabolic breakdown products in serum (e.g., cyclosporin, vancomycin), or to profile microbial isolates for novel drug-producing strains. 

Independently horn us at Sandoz Laboratories, Agathos and Lee (30) studied the influence of amino acids on the production of CyA by T. inflatum and found an enhancing effect of externally supplied L-valine in a chemically defined medium, raising the final CyA titer to 710 mg/liter, compared with only 130 mg/liter without L-valine supplementation. Furthermore, Agathos and Chun refxirt that immobilization of T. inflatum spores into porous celite beads results in an up to threefold higher cyclosporin formation than for the free cell culture (31). 

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