EFFECT OF CYCLOSPORIN-A AS AN IMMUNOSUPPRESSIVE DRUG ON ISLET CELLS TRANSPLANTATION IN MICE

2008 ◽  
Vol 19 (Issue A-2) ◽  
pp. 109-118
Author(s):  
ASHRAF SEIDA ◽  
MAHMOUD GABR ◽  
GABR EZZ EL-GAMAL ◽  
HASSAN IBRAHIM ◽  
MOHAMED EL-GHARIB
Keyword(s):  
Cyclosporin A ◽  
Islet Cells ◽  
Immunosuppressive Drug

scholarly journals Cyclosporin A augments angiotensin II-stimulated rise in intracellular free calcium in vascular smooth muscle cells

1987 ◽  
Vol 248 (3) ◽  
pp. 883-887 ◽  
Author(s):  
J Pfeilschifter ◽  
U T Rüegg
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cyclosporin A ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Immunosuppressive Drug ◽  
Free Calcium ◽  
Cytosolic Free Calcium

Pretreatment of rat vascular smooth muscle cells with the immunosuppressive drug cyclosporin A caused concentration- and time-dependent increases in both the amplitude and duration of the angiotensin II-induced rise in cytosolic free calcium, as measured with quin 2. Cyclosporin A had no significant effect on basal quin 2 fluorescence. However, cyclosporin A increased the basal 45Ca2+ influx. This stimulation of 45Ca2+ influx was not blocked by nifedipine (10(-6) M). Cyclosporin A also augmented the angiotensin II-stimulated influx and efflux of 45Ca2+. These results demonstrate that cyclosporin A increases the permeability of the plasma membrane for Ca2+ and also augments the angiotensin II-induced increases in cytosolic free calcium.

Simplified liquid-chromotographic analysis for cyclosporin A, and comparison with radioimmunoassay.

1983 ◽  
Vol 29 (1) ◽  
pp. 180-183 ◽  
Author(s):  
S G Carruthers ◽  
D J Freeman ◽  
J C Koegler ◽  
W Howson ◽  
P A Keown ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
High Performance ◽  
Chromatographic Method ◽  
Biological Fluids ◽  
High Performance Liquid Chromatographic ◽  
Immunosuppressive Drug ◽  
Internal Standards ◽  
Liquid Chromatographic Method ◽  
The Difference ◽  
Liquid Chromatographic

Abstract We describe a simplified isocratic "high-performance" liquid-chromatographic method for measuring a new immunosuppressive drug, cyclosporin A, in biological fluids with use of its analogs cyclosporin C and cyclosporin D as internal standards. The method is reproducible and accurate and appears to be specific for cyclosporin A; the detection limit is 31 micrograms/L. The chromatographic measurements of the concentration of cyclosporin A in serum of patients receiving the drug were invariably lower than those by radioimmunoassay and the difference became more pronounced the greater the period of time after dosing. Because measurements of cyclosporin A in serum standards were almost identical with both techniques, the differences between the two sets of results for patients' samples suggests that the radioimmunoassay is nonspecific and measures metabolites of cyclosporin A.

Blockade of endothelium-dependent responses in conscious rats by cyclosporin A: effect of L-arginine

1993 ◽  
Vol 264 (3) ◽  
pp. H708-H714 ◽  
Author(s):  
M. J. Gallego ◽  
A. Lopez Farre ◽  
A. Riesco ◽  
M. Monton ◽  
S. M. Grandes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Amino Acid ◽  
Atrial Natriuretic Peptide ◽  
Endothelial Function ◽  
Cyclosporin A ◽  
Wistar Rats ◽  
Immunosuppressive Drug ◽  
Simultaneous Administration ◽  
Harmful Effects ◽  
Functional Alteration

This study was undertaken to examine the effect of the major immunosuppressive drug, cyclosporin A (CyA), on endothelial function. Conscious Wistar rats, treated with CyA (25 mg.kg-1 x day-1 im for 15 days), developed an inhibition of the endothelium-dependent acetylcholine (ACh)-mediated vasodilation, diuresis, natriuresis, and guanosine 3',5'-cyclic monophosphate excretion. The response to two endothelium-independent agents, i.e., sodium nitroprusside and atrial natriuretic peptide was preserved in similarly treated rats. The toxic effects of CyA were acutely overcome by the administration of the amino acid L-arginine (L-Arg), a source of substrate for nitric oxide. Moreover, the simultaneous administration of L-Arg (200 mg/kg ip for 15 days) significantly prevented the functional effects of CyA toxicity. The present data suggest that, in early stages of CyA toxicity, the predominant functional alteration occurs at the endothelial level. The reversibility of such alteration by L-Arg opens the possibility for further strategies aimed to reduce the harmful effects of CyA.

Effect of rapamycin on the cyclosporin A–resistant CD28-mediated costimulatory pathway

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4517-4524 ◽  
Author(s):  
Paritosh Ghosh ◽  
Meredith A. Buchholz ◽  
Shingo Yano ◽  
Dennis Taub ◽  
Dan L. Longo
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cyclosporin A ◽  
T Cell Activation ◽  
Messenger Rna ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Immunosuppressive Drug ◽  
Receptor Interaction

The consequences of T-cell activation depend exclusively on costimulation during antigen–T-cell receptor interaction. Interaction between the T-cell coreceptor CD28 and its ligand B7 during antigen-antigen receptor engagement results in full activation of T cells, the outcomes of which are proliferation and effector functions. The ability of CD28 to costimulate the production of interleukin-2 (IL-2) explains the importance of this costimulation. The signaling event mediated by CD28 engagement has been proposed to have 2 components: one is sensitive to the immunosuppressive drug cyclosporin A (CsA), and the other one is CsA-resistant. In this report, we demonstrate that the CsA-resistant pathway is sensitive to the immunosuppressive drug rapamycin. Treatment with rapamycin blocked IL-2 production after activation of human peripheral blood T cells with phorbol ester (PMA) and anti-CD28 (CsA-resistant pathway), whereas this drug did not have any effect on PMA plus ionomycin stimulation (CsA-sensitive pathway). The inhibitory effect of rapamycin was on messenger RNA stability and translation, rather than on IL-2 transcription or protein turnover.

scholarly journals Effect of cyclosporin A on immunological response in lungs of guinea pigs infected with Trichinella spiralis.

2002 ◽  
Vol 49 (1) ◽  
pp. 233-247 ◽  
Author(s):  
Jolanta M Dzik ◽  
Zbigniew Zieliński ◽  
Barbara Gołos ◽  
Elzbieta Jagielska ◽  
Mariusz Wranicz ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Cyclosporin A ◽  
Guinea Pigs ◽  
Trichinella Spiralis ◽  
Early Period ◽  
Immunological Response ◽  
Lavage Fluid ◽  
Immunosuppressive Drug ◽  
Superoxide Anion Production ◽  
Inos Protein

The effects of cyclosporin A (CsA), a potent immunosuppressive drug with antiparasitic activity, on the innate immunological response in guinea pig lungs during an early period (6th and 14th days) after T. spiralis infection were studied. CsA treatment of T. spiralis-infected guinea pigs caused a significant attenuation of immunological response in lungs by decreasing lymphocyte infiltration into pulmonary alveolar space, inhibiting alveolar macrophage superoxide anion production and lowering both the production of NO metabolites measured in bronchoalveolar lavage fluid and expression of the iNOS protein in lung homogenates, allowing us to speculate that the T. spiralis-dependent immunological response is dependent on lymphocyte T function. Interestingly, CsA itself had a pro-inflammatory effect, promoting leucocyte accumulation and macrophage superoxide production in guinea pig lungs. This observation may have a relevance to the situation in patients undergoing CsA therapy. Macrophage expression of the iNOS protein, evaluated by immunoblotting was not influenced by treatment of animals with CsA or anti-TGF-antibody, indicating different regulation of the guinea pig and murine enzymes.

scholarly journals Potential Role of Cyclosporin a in Corneal Grafting

1981 ◽  
Vol 74 (11) ◽  
pp. 810-813 ◽  
Author(s):  
P A Hunter
Keyword(s):  
Cyclosporin A ◽  
Intramuscular Injection ◽  
Potential Role ◽  
Immunosuppressive Drug ◽  
Corneal Allograft ◽  
Corneal Grafting ◽  
Corneal Transplants ◽  
Series Of Experiments ◽  
Single Set

The immunosuppressive drug cyclosporin A has been shown to be effective in preventing corneal allograft reactions in rabbits when administered by intramuscular injection. However, when used systemically in man, the drug may have potentially serious side effects and a series of experiments has therefore been performed in order to investigate the use of topically applied cyclosporin A in rabbit corneal transplants. Using a single set model of the corneal allograft reaction, two groups of rabbits treated with topically applied cyclosporin A for periods of four and thirteen weeks respectively showed significantly increased graft survival compared with untreated controls (P < 0.001).

scholarly journals An endoplasmic reticulum-specific cyclophilin.

1991 ◽  
Vol 11 (7) ◽  
pp. 3484-3491 ◽  
Author(s):  
K W Hasel ◽  
J R Glass ◽  
M Godbout ◽  
J G Sutcliffe
Keyword(s):  
Endoplasmic Reticulum ◽  
Cyclosporin A ◽  
Immunoblot Analysis ◽  
Immunosuppressive Drug ◽  
Cdna Clones ◽  
Cell Fractionation ◽  
Sequence Identity ◽  
Degenerate Oligonucleotide ◽  
Cell Membrane Proteins ◽  
T Cell Membrane

Cyclophilin is a ubiquitously expressed cytosolic peptidyl-prolyl cis-trans isomerase that is inhibited by the immunosuppressive drug cyclosporin A. A degenerate oligonucleotide based on a conserved cyclophilin sequence was used to isolate cDNA clones representing a ubiquitously expressed mRNA from mice and humans. This mRNA encodes a novel 20-kDa protein, CPH2, that shares 64% sequence identity with cyclophilin. Bacterially expressed CPH2 binds cyclosporin A and is a cyclosporin A-inhibitable peptidyl-prolyl cis-trans isomerase. Cell fractionation of rat liver followed by Western blot (immunoblot) analysis indicated that CPH2 is not cytosolic but rather is located exclusively in the endoplasmic reticulum. These results suggest that cyclosporin A mediates its effect on cells through more than one cyclophilin and that cyclosporin A-induced misfolding of T-cell membrane proteins normally mediated by CPH2 plays a role in immunosuppression.

846 Is the Primary Immunosuppressive Drug (Cyclosporin a or Tacrolimus) Playing a Role on the Response to Antiviral Treatment for Post-Transplant HCV Recurrence?

2012 ◽  
Vol 142 (5) ◽  
pp. S-934
Author(s):  
Vittoria Vero ◽  
Senzolo Marco ◽  
Luisa Pasulo ◽  
Francesca Romana Ponziani ◽  
Raffaella Viganò ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Antiviral Treatment ◽  
Immunosuppressive Drug ◽  
Post Transplant

An endoplasmic reticulum-specific cyclophilin

1991 ◽  
Vol 11 (7) ◽  
pp. 3484-3491
Author(s):  
K W Hasel ◽  
J R Glass ◽  
M Godbout ◽  
J G Sutcliffe
Keyword(s):  
Endoplasmic Reticulum ◽  
Cyclosporin A ◽  
Immunoblot Analysis ◽  
Immunosuppressive Drug ◽  
Cdna Clones ◽  
Cell Fractionation ◽  
Sequence Identity ◽  
Degenerate Oligonucleotide ◽  
Cell Membrane Proteins ◽  
T Cell Membrane

Cyclophilin is a ubiquitously expressed cytosolic peptidyl-prolyl cis-trans isomerase that is inhibited by the immunosuppressive drug cyclosporin A. A degenerate oligonucleotide based on a conserved cyclophilin sequence was used to isolate cDNA clones representing a ubiquitously expressed mRNA from mice and humans. This mRNA encodes a novel 20-kDa protein, CPH2, that shares 64% sequence identity with cyclophilin. Bacterially expressed CPH2 binds cyclosporin A and is a cyclosporin A-inhibitable peptidyl-prolyl cis-trans isomerase. Cell fractionation of rat liver followed by Western blot (immunoblot) analysis indicated that CPH2 is not cytosolic but rather is located exclusively in the endoplasmic reticulum. These results suggest that cyclosporin A mediates its effect on cells through more than one cyclophilin and that cyclosporin A-induced misfolding of T-cell membrane proteins normally mediated by CPH2 plays a role in immunosuppression.

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