Cyclosporin A and

Cyclosporin A forms white prismatic crystals from acetone and is only slightly soluble in water and saturated hydrocarbons, but is very soluble in methanol, ethanol, acetone, and diethyl ether. Optical and nmr data on cyclosporins and x-ray crystallographic data on cyclosporin A and an io do derivative have been reviewed (273,275). 

Calcineurin is involved in cardiac hypertrophy and in cognitive and behavioral defects in the brain. Inhibitors of calcineurin such as cyclosporine A and FK 506 are used clinically in transplant rejection and autoimmune diseases. 

The introduction of PP2B (calcinemin) inhibitors revolutionized kidney transplantation. Cyclosporine A and tacrolimus (FK506) are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. Cyclosporine A was in use clinically long before its mechanism of action was elucidated. 

Playfair J.H.L. 992) Immunology at a Glance, 5th edn. Oxford Blackwell Scientific Publications. Roitt I.M. 99A) Essential Immunology, 8th edn. Oxford Blackwell Scientific Publications. Schreiber S.L. Crabtree G.R (1992) The mechanisms of action of cyclosporin A and FK506. Immunol Today, 13, 136-142. 

K Osann, P Sweet, LM Slater. (1992). Synergistic action of cyclosporin A and verapamil on vincristine and daunorubicin resistance in multidrug-resistant human leukemia cells in vitro. Cancer Chemother Pharmacol 30 152-154. 

Koal et al. (2004) measured four immunosuppressants (cyclosporine A, tacrolimus, sirolimus, and everolimus) in whole blood samples from transplant recipients. The samples were treated first with a protein precipitation step. The supernatant was extracted with a Poros Rl/20 perfusion column (30 x 2.1 mm, 20 tm, Applied Biosystems, Darmstadt, Germany) online. A Luna phenyl hexyl column (2 x 50 mm, Phenomenex, Schaffenburg, Germany) was used for separation. The total run time was 2.5 min. The lower limit of quantitation was 10 ng/mL for cyclosporine A and 1 ng/mL for the other three analytes. 

A phase II clinical study of FTY720 in de novo renal transplant patients showed superior efficacy of FTY720 compared to mycophenolate mofetil, if combined with cyclosporine A and steroids [57], In a 1 year, multicentre,... 

Boelsterli, U.A., Bouis, P., Brouillard, J.F. and Donatsch, P. (1988). In vitro toxicity assessment of cyclosporin A and its analogs in a primary rat hepatocyte culture model. Toxicol. Appl. Pharmacol. 96 212-221. 

Two structurally unrelated immunosuppressant drugs, cyclosporin A and FK506, have been shown to bind to separate proteins, which have in common the ability to catalyse the interconversion (8) of the cis and trans rotamers of peptidyl-proline bonds of peptide substrates. A profound change in the conformation, and hence the shape and binding properties of the protein, may result. The mechanism of this isomerization appears, on the basis of recent work (Rosen et al., 1990 Van Duyne et al., 1993 Albers et al., 1990), to involve simple twisting about the amide bond, rather than such alternatives as conversion to a C-N single bond by addition of a nucleophile to C=0.y The proteins which catalyse the reaction may be... 

RM Wenger. Synthesis of cyclosporine. Total synthesis of cyclosporin A and cyclosporin H, two fungal metabolites isolated from the species Tolypocladium infla-tum Gams. Helv Chim Acta 67, 502, 1984. 

Retina-to-blood efflux transport P-Glycoprotein (mdr 1 a) Cyclosporin A and others + TR-iBRB [14,19, 45, 53, 54]... 

Kiessig et al. studied the interaction of the immunosuppressant drug cyclosporin A and some derivatives to its cellular receptor protein cyclo-philin (26). The cyclophilin-cyclosporin A complex mediates the immunosuppressive action of cyclosporin A by inhibition of the phosphatase calci-neurin. Using ACE in the equilirium-mixture mode, a separation of the cyclophilin-cyclosporin A complex and the unbound cyclophilin was achieved. The approach allowed a qualitative estimation of the binding affinity of cyclosporin A derivatives compared to cyclosporin A. For the calculation of binding constants, electrophoretically mediated microanalysis was applied. 

Gerards AH et al Cyclosporine A monotherapy versus cyclosporine A and methotrexate combination therapy in patients with early rheumatoid arthritis A double blind randomised placebo controlled trial. Ann Rheum Dis 2003 62 291. [PMID 12634224]... 

Clinically, we address this topic by high doses of steroids and massive anti-inflammatory measures like topical steroids, cyclosporine A, and rinsing of the eye under the presumption that it would remove the mediator-rich transudates [52] that are enriched with proteolytic enzymes like the V-actyl-glucosaminidase. Further studies have observed high IL-8 and IL-1 rates in corneas after eye bums [53]. These data could be reproduced in the EVEIT system with IL-8 being upregulated for NaOH and also for the sodium lauryl sulfate (SLS) (Eig. 5.17) in a dose-dependent manner. 

Following convention we will give the letter A to cyclosporin A and D to cyclosporin D as used in the internal standard ... 

Starzl TE, Klintmalm GB, Porter KA, Iwatsuki S. 1981. Liver transplantation with use of cyclosporin a and prednisone. NEJM. 305 266-269. 

Rezzani R. Cyclosporine A and adverse effects on organs histochemical studies. Prog Histochem Cytochem. 2004 39 85-128. 

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