ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of cyclosporine (CsA) on renal function and morphology have been studied in the rat after unilateral nephrectomy and warm renal ischemia. There is evidence of an enhanced CsA nephrotoxic effect after unilateral nephrectomy alone and of an additive or synergistic effect of CsA and renal ischemia upon renal function and morphology. These enhanced effects are most evident after longer periods of ischemia (60 min) and with higher doses of CsA (25 mg/kg/day). The findings may be relevant to clinical practice and suggest that the nephrotoxic effects of CsA upon the door kidney may be greatest when there is coincident renal damage from other causes.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

To investigate the interaction of cyclosporine nephrotoxicity and renal ischemia, an animal model in rats with bilateral renal artery clamping was used. Rats given cyclosporine had a lower rate of recovery from ischemia. However, the percentages of reduction in glomerular filtration rate in vehicle and cyclosporine groups were the same in sham-operated or ischemically treated group. This suggests a superimposition of cyclosporine nephrotoxicity on the recovering kidneys rather than synergistic potentiation between ischemia and cyclosporine nephrotoxicity.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

A method is described for continuous administration of immunosuppressive drugs directly into rate renal allografts. The drug is given via a catheter, introduced into the suprarenal or testicular artery of the transplanted kidney. The cannula is connected to an implantable osmotic minipump that delivers an immunosuppressive drug with continuous flow for 13 days. It is demonstrated that the technique as such has no detrimental or enhancing effects on renal allograft survival. Depending upon the pharmacokinetic properties of the drug administered, this technique allows a more or less selective treatment of renal allograft rejection.The method was used to test the effect of intrarenal administration of prednisolone on renal allograft survival. Intrarenal administration of this drug appeared to be superior to any other way of administration tested.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Rabbit kidneys were stored for 24 or 48 hr at 0$$C after single-passage vascular flush with 30 ml of cold hypertonic citrate solution or 0.9% isotonic sodium chloride solution. They were then subjected to in vitro biochemical assay for evidence of free-radical damage immediately after storage or after they had been orthotopically autotransplanted and reperfused with blood in vivo for 60 min. Kidney homogenates were incubated at 37$$C and assayed for fluorescent conjugated Schiff bases as indicators of lipid peroxidation, as well as for superoxide dismutase activity and reduced and oxidized glutathione.In kidneys flushed with hypertonic citrate, no evidence of peroxidation could be detected immediately after storage for 24 or 48 hr. However, after in vivo reperfusion significantly more peroxidation (P<0.01) was evident. Storage in isotonic saline solution produced still higher levels of peroxidation damage whether reperfused or not (P<0.001). Schiff base formation was inversely proportional to the reduced and oxidized glutathione levels measured. No changes in superoxide dismutase levels could be detected. It is concluded that lipid peroxidation is important during cold ischemia but most damage occurs during the 60-min of reperfusion in vivo immediately after transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Rats given a blood transfusion do not reject a subsequent kidney allograft from the same donor strain. This effect is strain-specific so that pretransplant blood transfusion from a LEW (RT11) rat will protect a LEW kidney in a DA (RT1***) recipient but not a PVG/c (RT1c) kidney. The same is true in other combinations. Using DA or PVG.RT1*** congenic recipients we have shown that sharing of all or part of the MHC or of minor alloantigens by the blood transfusion and kidney transplant donors is sufficient to prolong allograft survival. Activation of suppression against minor alloantigens appears to require two signals: one is the minor alloantigen and the other may be a major histocompatibility complex alloantigen.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Four patients with progressive extensive chronic graft-versus-host disease or dose-limiting toxicity on conventional therapy (cyclophosphamide + prednisolone) were treated with a regimen of cyclosporine + prednisolone as induction therapy and cyclosporine as maintenance therapy. All 4 showed clinical improvement and 3 of 4 are alive at 9 months. The incidence of infections was not affected by this regimen, but steroid requirements were reduced.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The immunological events mediated by, and antigen specificity of, allograft-bound lymphocytes (ABLs) are poorly understood. To further define the role of anti-body-mediated rejection, a rejected allograft from a patient with primary anti-TBM disease was sterilely minced and pressed through a microscreen. The ABLs were isolated by density gradient centrifugation. Using this technique, 8.5x106ABLs were isolated. Then 1x106washed ABLs/ml were suspended in RPMI 1640 with 20% fetal calf serum and cultured in microtiter plates with media only, or with pokeweed mitogen plates with media only, or with pokeweed mitogen (PWM) (100 $mUg/culture). The cells were incubated for 7 days and supernatants were collected and assayed for total IgG and IgM by a solid-phase enzyme immunoassay (EIA) and reactivity with normal human kidney targets by indirect immunofluorescence (IF) and immunoperoxidase (IP) techniques. Total IgG production was 500 ng/ml for both spontaneous and PWM stimulated cells. No IgM production was detected. IF and IP studies demonstrated IgG-anti-TBM antibodies in the spontaneous supernatants only. IgG antibodies reactive with peritubular capillaries (anti-PTC) were also noted. IgG-anti-TBM anti-bodies and antibodies reactive with arterioles were subsequently demonstrated by direct immunofluorescence techniques in the rejected allograft. Analysis of serum samples obtained at the time of allograft rejection showed no IF or IP reactivity with the Kidney targets. Subsequent analysis of anti-TBM production by the patient's peripheral blood mononuclear cells (PBMs) showed IgM-anti-TBM only. These studies suggest that the IgG-anti-TBM and IgG-anti-PTC antibodies reactive with the allograft resulted from in situ antibody production by ABLs; the role of anti-TBM antibodies in mediating the AR is unclear, but their presence suggests recurrence of the original disease in the allograft. Anti-PTC antibodies could be important in mediation of the vascular AR.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We randomized 158 recipients of cadaver renal allografts to cyclosporine-prednisone (83) or antilymphocyte globulin-azathioprine-prednisone (75) to evaluate: (1) the effects of immunosuppression and pretransplant risk factors on the incidence of delayed graft function, (2) the effects of immunosuppression on the resolution of delayed graft function, and (3) the effects of delayed graft function and pretransplanted risk factors on patient and graft survival. Cyclosporine did not increase the incidence of delayed graft function, compared with ALG-azathioprine-treated patients (33% versus 27%,P=0.550) but doubled the mean ($$SD) duration of oil-guria (11.8$$11.0 versus 5.9$$3.2 days,P=0.002) and the number of required dialyses (6.6$$7.6 versus 3.2$$1.3,P=0.031). Retransplanted patients had a higher incidence of delayed graft function that recipients of primary grafts in both the cyclosporine (82% versus 25%,P=0.001) and ALG-azathioprine (55% versus 22%,P=0.025) treatment groups. The presence of delayed function reduced one-year graft survival from 89% in all patients without delayed function to 72% (P=0.011) in all patients with delayed function. Cyclosporine-treated patients had a slightly, but not significantly better one-year graft survival rate than ALG-azathioprine treated patients both with (73% versus 68%,P=0.750) and without (92% versus 82%,P=0.069) delayed graft function. A preservation time longer than 24 hr did not increase the incidence of delayed graft function in cyclosporine-treated patients (34% versus 32%,P=0.811) or ALG-azathioprine-treated patients (27% versus 27%,P=0.902). Cyclosporine-treated patients given kidneys with greater than 24 hr of preservation time had reduced graft survival only when delayed graft function occurred (67% versus 92%,P=0.009). In conclusion, (1) cyclosporine did not increase the incidence of delayed graft function over ALG-azathioprine treatment; (2) cyclosporine did significantly slow recovery of kidneys with delayed function; (3) delayed graft function correlated with poorer graft survival rate in both treatment groups; but (4) prolonged preservation time did not increase the incidence of delayed graft function or reduce graft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Cyclosporine (CsA), a potent immunosuppressant for the prevention of transplant rejection, modulates T lymphocyte activation by blocking antigen stimulation and the production of interleukin-2. The mode of action by which CsA generates this immunosuppressive effect is unknown. We have studied two early intracellular enzymes associated with mitogen activation. They include calcium/phospholipid-dependent protein kinase (cAMPd PK). Changes in protein kinase activation were correlated with the immunosuppression of polyamine and DNA synthesis measured by ornithine decarboxylase (ODC) induction and 3H-thymidine incorporation, respectively. These studies utilized murine T cell tumor lines sensitive to the effects of CsA.Similar to the mitogen activation of human peripheral blood lymphocytes, CsA was capable of inhibiting the induction of ODC and3H-thymidine uptake of T cell tumor lines cultured with either fresh serum or mitogen. In constrast, C-kinase and cAMPd PK activation stimulated by the addition of fresh serum was not affected by CsA. Further, CsA did not inhibit the direct activation of C-kinase with phorbol esters or the activation of cAMPd PK with exogenous cAMP.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID