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E Thervet

Publications and source records attributed to E Thervet.

At least 19 recordsLinked to original sources
PubMed2006

Role of P-glycoprotein in cyclosporine cytotoxicity in the cyclosporine-sirolimus interaction.

Cyclosporine nephrotoxicity remains a major side effect in solid organ transplantation, and can be exacerbated by concomitant administration of sirolimus. Cyclosporine and sirolimus are P-glycoprotein (Pgp) substrates. We hypothesized that the Pgp activity level may affect cyclosporine cytotoxicity by interfering with the ability of Pgp to remove cyclosporine from within tubular cells, and that an interaction between cyclosporine and sirolimus on Pgp function may explain the enhancement of cyclosporine nephrotoxicity by sirolimus. Cyclosporine cytotoxicity was evaluated in primary cultures of normal human renal epithelial cells (HRECs) by cell viability and cytotoxicity assays. Verapamil, quinine, PSC833, and PGP-4008 were used as Pgp inhibitors. Rhodamine-123 (R-123), a fluorescent substrate of Pgp, was used to assess Pgp-mediated transport. Cellular cyclosporine concentration was measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Pgp expression and function were confirmed in HRECs and cyclosporine and sirolimus were shown to be Pgp inhibitors in this model. Verapamil-induced inhibition of Pgp led to a significant increase in cellular concentration of cyclosporine (P<0.05). Cyclosporine exerted a concentration-dependent cytotoxic effect on HRECs that was significantly increased by inhibition of Pgp activity. Sirolimus exerted an inhibitory effect on R-123 efflux in HRECs and increased cellular cyclosporine concentrations in a dose-dependent manner. These data demonstrate that Pgp plays a critical role in protecting renal epithelial cells from cyclosporine toxicity. The inhibitory effect of sirolimus on Pgp-mediated efflux and the cellular concentration of cyclosporine could explain the exacerbation of cyclosporine nephrotoxicity observed clinically.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

[Minimization of immunosuppression].

Minimization protocols: The goal of minimization protocols is to reduce the load of immunosuppressant agents after transplantation. Besides the basic medical objective of reduced deleterious effects of long-term immunosuppression, minimization also has an economic impact. Discontinuation of corticosteroid therapy: Results obtained with different minimization protocols have shown that any interruption of corticosteroid therapy, even if associated with the new immunosuppressants, should be conducted carefully in selected patients, tapering off late after transplantation. Mycophenolate-mofetil (MMF): MMF withdraw may be risked and the beneficial effect of discontinuation remains to be demonstrated. Calcineurin inhibitors: Most immunosuppression protocols use cyclosporine. The benefit obtained by totally discontinuing cyclosporine in stabilized patients does not outbalance the risks induced by withdrawal. However, in this population, MMF can be useful for tapering down cyclosporine. In patients with altered renal function, introduction of MMF or sirolimus can allow a reduction in dosage or complete withdrawal of cyclosporine.

Adrenal Cortex Hormones↗
PubMed2001

[What is new on transplantation in 2001?].

IMMUNOSUPPRESSIVE THERAPY: Intravenous immunoglobulins have demonstrated their value for highly immunized cross-match positive transplantation candidates. Graft rejection during the first two post-transplantation weeks can be avoided with CMPATH-1H, humanized anti-CD52 monoclonal antibody, which produces major and persistent T- and B-cell as well as monocyte depletion. FTY 720 is well tolerated and has demonstrated its efficacy in preventing acute rejection. Sirolimus would have an antiatheromatous effect. Attempts to minimize immunosuppression should be followed for several months. OTHER NEW DEVELOPMENTS: There has been considerable interest in Langerhans islet transplantation. Work also concerns follow-up techniques used to diagnosis rejection. FUNDAMENTAL SCIENCE: New advances in basic science that should have an impact on transplantation have been made in the area of lymphocyte activation, toll-like receptor structures, and germinal and stem cells, as well as in the areas of essay methods and gene therapy.

Alemtuzumab↗
PubMed2001

[New immunosuppressive drugs and diabetes].

Glucocorticoïds, calcineurin inhibitors (especially tacrolimus) and the combination of both are responsible for the occurrence of diabetes mellitus after organ transplantation. These drugs induce both insulin resistance and insulinopenia. Risks factors are well identified: high doses of immunosuppressive drugs, genetic background, age and weight excess. Long-term consequences seem to be as deleterious as those of other types of diabetes mellitus. Modulating the doses of immunosuppressive drugs is efficient in decreasing insulin requirement in transplant recipients but only individualization of immunosuppression taking risks factors into account will permit to decrease the incidence of this side-effect.

Diabetes Mellitus↗
PubMed2001

[Hand-assisted laparoscopic bi-nephrectomy for refractory arterial hypertension in kidney transplantation].

OBJECTIVE: The authors report their preliminary experience of a manually assisted laparoscopic bilateral nephrectomy technique for refractory hypertension in renal transplant recipients. MATERIAL AND METHODS: Between April and May 1999, 2 laparoscopic bilateral nephrectomies were performed with manual assistance using the Hand-Port. One patient was operated 4 months before renal transplantation and the other was operated 13 months after renal transplantation. Both patients presented severe hypertension refractory to several antihypertensive drugs. An 8 cm midline supra-umbilical incision and 3 trocars were necessary. One hand was introduced into the abdominal cavity via the Hand-Port at the beginning of the operation. The intra-abdominal hand assisted all phases of dissection of the kidney and control of vessels. The renal vessels and ureter were clipped. The kidneys were removed by the intra-abdominal hand through the supra-umbilical incision. RESULTS: Operating times were 200 min and 130 min. Blood loss was 220 ml. No conversion was performed. The duration of major postoperative analgesics was 3 days. Length of hospital stay was 6 days and 7 days. There were no complications. Blood pressure was controlled by bilateral nephrectomy in both cases, with significant reduction of antihypertensive therapy. One year after the operation, both patients were satisfied with the aesthetic result. CONCLUSIONS: Laparoscopic bilateral nephrectomy manually assisted by the Hand-Port is an alternative to open bilateral nephrectomy. Larger series are necessary to evaluate the morbidity of this technique.

Adult↗
PubMed2001

[Pharmacology of mycophenolate mofetil: recent data and clinical consequences].

New insights have been recently obtained about pharmacokinetic and pharmacodynamic characteristics of mycophénolate mofetil (MMF). One of the already described MPA metabolite, the acylglucuronide of MPA may be both active and responsible for some side-effects. Glucuronidation is mediated by at least two uridine diphosphate glucuronosyltransferase (UGT) forms, namely UGT1A8 and UGT1A10 whose variability could explain the inter- and intra-individual variability of MMF metabolism. MPA pharmacokinetic data in dialyzed patients or in patients with chronic renal failure are now available. After renal transplantation, MPA levels vary between immediate post-transplant period, at three months and at two years. The target enzyme is inosine monophosphate dehydrogenase (IMPDH). The genes of the two IMPDH isoforms have been cloned. The bicyclic ring system of MPA packs underneath the hypoxanthine ring of IMPDH, thereby trapping this covalent intermediate of the enzymatic reaction. After renal transplantation, a randomized trial has shown that clinical efficacy is correlated with MPA AUC but side effects are correlated with MMF dosage. When associated with cyclosporine, there is a significant decrease of MPA level. Better knowledge of MMF metabolism, of variability factors and target levels to reach in clinical practice should allow a better use of MMF.

Animals↗
PubMed2000

Development of cytomegalovirus resistance to ganciclovir after oral maintenance treatment in a renal transplant recipient.

The emergence of a resistant strain is a theoretical threat after extensive use of antiviral drugs. We report the emergence of a ganciclovir-resistant cytomegalovirus (CMV) strain in a kidney transplant recipient during oral ganciclovir maintenance treatment. The patient was treated by oral ganciclovir for 2 months after successful treatment of CMV primary infection by intravenous ganciclovir. He developed a new episode of CMV infection with no clinical response to intravenous ganciclovir. The CMV isolate exhibited both phenotypic and genotypic resistance to ganciclovir. The CMV isolate was constituted of a mixture of strains, with and without a mutation at codon 460 of the UL97 gene. The clinical condition improved when mycophenolate mofetil (MMF) was discontinued, and a short course of intravenous globulin was added to ganciclovir. The emergence of the CMV strain could be secondary to more potent immunosuppression provide by MMF or subtherapeutic level obtained during oral ganciclovir treatment. We believe that ganciclovir resistance must be part of the differential diagnosis when a patient relapses or fails to respond to ganciclovir treatment.

Administration, Oral↗