Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FK506 trough levels were measured by ELISA in paired whole-blood and plasma samples in 59 liver transplant recipients. Patients with nephrotoxicity had higher FK506 whole-blood and plasma levels (27.5 +/- 3.2 ng/ml and 1.44 +/- 0.14 ng/ml) than patients with stable liver function (15.2 +/- 2.1 ng/ml and 0.98 +/- 0.15 ng/ml, P < 0.05 and P < 0.01, respectively). Patients with acute rejection had FK506 whole-blood and plasma levels within the same range as patients with stable liver function. Patients with severe neurotoxicity had significantly higher FK506 whole-blood and plasma levels (31.3 +/- 6.8 ng/ml and 3.9 +/- 1.4 ng/ml) in comparison with patients with mild-to-moderate neurotoxicity (18.1 +/- 2.4 ng/ml and 1.1 +/- 0.13 ng/ml) (P = 0.048 and P < 0.001, respectively). Long-term use of FK506 was associated with a significant reduction in glomerular filtration rate at 1-year posttransplant in patients on primary FK506 treatment (33%, P < 0.001). The reduction in glomerular filtration rate correlated with the yearly mean FK506 plasma but not with whole-blood levels or FK506 dose. There was a correlation between FK506 whole-blood and plasma levels (r = 0.713, P < 0.001) but not between the levels (whole blood or plasma) and FK506 dose (mg/day or mg/kg/day). The mean FK506 whole-blood and plasma levels were 14.1 +/- 0.26 ng/ml and 0.96 +/- 0.75 ng/ml, respectively. There was a large intra- and interpatient variability in the ratio between whole-blood and plasma levels (range 1.0-73.5), with a mean ratio of 18.0 +/- 0.28 (+/- SEM). In conclusion, monitoring of FK506 trough levels is of importance to avoid nephro- and neurotoxicity, but monitoring is only of limited help to avoid acute rejection. Monitoring of FK506 levels in plasma seems to be superior to that in whole blood.
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PMID:FK506 trough levels in whole blood and plasma in liver transplant recipients. Correlation with clinical events and side effects. 751 1

The mechanism by which FK506 (FK) prevents hepatic injury induced by ischemia/reperfusion was studied. Adult Sprague-Dawley rats were subjected to 60-min normothermic liver ischemia. Animals were divided into two groups: group I, controls, saline vehicle treatment; group II, FK treatment. FK (1 mg/kg/day, p.o.) was given for 4 consecutive days prior to inducing ischemia. In addition to a survival study, plasma levels of endotoxin and serum activities of tumor necrosis factor-alpha (TNF) and aspartate aminotransferase (AST) were assessed in the blood collected from suprahepatic vena cava. Results showed: (1) FK therapy significantly improved 7-day survival (80.0%) compared with nontreated animals (50.0%, p < 0.05); (2) both TNF and endotoxin were elevated following reperfusion, reaching maximum values at 3 h after reperfusion (217.0 +/- 40.6 and 280.5 +/- 31.4 pg/ml, respectively, in the control; mean +/- SEM), and (3) serum activities of TNF and AST following reperfusion were substantially suppressed with FK treatment, whereas FK did not reduce the rise in endotoxin. These findings suggest that suppression of TNF production in response to endotoxemia might account at least in part for the protective effect of FK against ischemia-induced hepatic injury.
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PMID:Evidence that FK506 alleviates ischemia/reperfusion injury to the rat liver: in vivo demonstration for suppression of TNF-a production in response to endotoxemia. 751 91

FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.
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PMID:Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat. 754 Sep 67

The major obstacle for successful xenotransplantation of islets to large animals and human diabetics is the host rejection. To address the rejection problem, we studied the efficacy of UV-B irradiation, cryopreservation and immunosuppression on the in vivo functional time and immunogenicity of adult porcine islets (PI) in outbred CD1 mice. Exposure of PI to UV-B irradiation between 300-1800J/M2 did not affect the cellular viability as assessed by fluorescein diacetate or their daily insulin secretion in vitro. Fresh PI normalized the blood glucose (BG) of diabetic CD1 mice for 3.1+/-0.6 (n = 8, mean+/-SEM) days. Islets treated with 600J/M2 UV-B irradiation or cryopreservation had similar graft functional times to fresh islets upon transplantation in diabetic CD1 mice. Immunosuppression with cyclosporin A (CsA), antilymphocyte serum (ALS) and FK506 prolonged the functional time of fresh pig islets to 7.9+/-0.9 (n = 9), 6.2+/-1.3 (n = 5) and 24.2+/-10.4 (n = 12) days, respectively. However, additional pretransplant treatment with either UV-B irradiation or cryopreservation did not further increase the functional time of pig islets in mice immunosuppressed with CsA. Furthermore, there was no apparent difference in the frequency of appearance of cytotoxic antibodies and antibody titers in the recipients of UV-B irradiated or cryopreserved pig islet compared with non-treated islets. The UV-B irradiation and cryopreservation of PI before transplantation with the present protocols did not appear to have significant effect on the islet immunogenicity when assessed by in vivo survival duration and anti-donor antibody titer production.
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PMID:Xenotransplantation of adult porcine islets in diabetic mice. A study of UVB irradiation, cryopreservation and immunosuppression on graft survival time. 976 81

In recent years, there has been growing evidence that tumor necrosis factor-alpha (TNF) plays an important role in the development of hepatic injury after ischemia-reperfusion. We have previously demonstrated that the immunosuppressants, cyclosporine, azathioprine and FK506 (FK), have a protective effect on warm ischemic injury of the rat liver. In the present study, we attempted to elucidate the mechanism for the beneficial effect of FK on liver ischemia, with special reference to the suppression of TNF production. After 60 min and 90 min of warm liver ischemia, the survival rates were significantly improved by FK pretherapy. This was associated with amelioration of hepatic injury, as assessed by histological examinations and determinations of serum AST and lipid peroxide levels in the liver. After 60 min of liver ischemia, TNF was measurable during the reperfusion period in the sera of the control animals, peaking of 6 h after reperfusion (123 +/- 15.8 pg/ml, mean SEM). In contrast, pretreatment with FK significantly suppressed the elevation of serum TNF levels at the same time point (75.8 +/- 13.1 pg/ml, P < 0.05). The present data showed that liver ischemia-reperfusion resulted in TNF production, and that FK could protect the liver from reperfusion injury by suppressing this production of TNF.
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PMID:FK 506 ameliorates normothermic liver ischemia in rats by suppressing production of tumor necrosis factor. 1462 4