Cyclosporin A (ciclosporin), a potent and clinically important immunosuppressive drug (Sandimmun), represents the main component of a group of over 25 closely related, cyclic undecapeptides produced by the fungus Tolypocladium inflatum. By feeding experiments using DL-alpha-allylglycine as precursor, specific incorporation in position 2 was attained leading to [Allylgly2]cyclosporin A. Exogenou...

In two consecutive prospective randomised trials cyclosporin A has been compared with conventional immunosuppressive therapy (azathioprine and steroids) and with cyclosporin combined with steroids. The present report is a 4 year review and includes 165 patients.Cyclosporin A alone had a significant advantage over conventional therapy at both 1 and 3 years (p = 0.02) for both patient and graft s...

Liver functional abnormalities were seen in 13 (19.7%) of 66 recipients of cadaveric renal homografts treated with cyclosporin A and prednisone. However, such presumed hepatotoxicity was a minor problem in the use of cyclosporin A. The complication was less frequent than that of nephrotoxicity, was as easily manageable with reductions in the cyclosporin A dosage, and generally did not cause cli...

The purpose of this study was to clarify the contribution of P-glycoprotein to the bioavailability and intestinal secretion of grepafloxacin and levofloxacin in vivo. Plasma concentrations of grepafloxacin and levofloxacin after intravenous and intraintestinal administration were increased by cyclosporin A, a P-glycoprotein inhibitor, in rats. The total body clearance and volume of distribution...

The use of cyclosporin is well established within the ophthalmology community, especially against sight threatening intraocular inflammation. It is well known however, that immunosuppression in general is a risk factor for the development of malignancy and numerous studies point to the risk imposed by cyclosporin. This article analyses and reviews all relevant studies with regard to the develop...

Anti-islet cell and anti-insulin antibody production was studies over a 12-mo period in 82 recently diagnosed diabetics randomly receiving either cyclosporin or placebo. Cyclosporin had only minimal effects on the production of anti-islet cell antibodies whether directed to islet cytoplasmic (immunofluorescence) or membrane (cytotoxicity assay) antigens even in patients undergoing remission. Th...

The in vitro effect of Cyclosporin A on the regulation of immunoglobulin production was investigated in 16 patients with primary biliary cirrhosis. A significant improvement in concanavalin A induced suppression of IgG and IgM producing cells was observed after prior incubation of mononuclear cells with 300 ng/ml Cyclosporin A for 30 minutes. No effect was seen on spontaneous or pokeweed mitoge...

Synaptic mechanisms of plasticity are calcium-dependent processes that are affected by dysfunction of mitochondrial calcium buffering. Recently, we observed that mice deficient in mitochondrial voltage-dependent anion channels, the outer component of the mitochondrial permeability transition pore, have impairments in learning and hippocampal synaptic plasticity, suggesting that the mitochondria...

Previous studies indicate that blood levels of cyclosporin-A are increased by concomittant administration of grapefruit juice in healthy subjects and patients. It was suggested that grapefruit juice could inhibit the metabolism of cyclosporin-A by CYP3A4, the predominant cytochrome P450 enzyme in the gut wall and liver. However, up to date, the mechanism of action of grapefruit juice has not be...

The use of cyclosporin A has contributed greatly to the success of organ transplantation. However, cyclosporin-associated side effects of hypertension, nephrotoxicity, and dyslipoproteinemia have tempered these benefits. Cyclosporin-induced dyslipoproteinemia may be an important risk factor for the accelerated atherosclerosis observed posttransplantation. Using a mouse model, we treated Swiss-W...