Analysis of the interactions of immunosuppressive drugs with cyclosporine in inhibiting DNA proliferation.

Abstract:

:Though the high immunosuppressive efficacy of cyclosporine has revolutionized clinical transplantation, renal, hepatic, and neural toxicities limit its therapeutic potential. One approach to this problem is to combine CsA therapy with immunosuppressive agents that act synergistically with it, thereby permitting lower doses and mitigating drug-induced toxicity. The present study examines the in vitro interactions of various immunosuppressive agents--namely, 6-mercaptopurine (6MP), dexamethasone (Dexa), FK506, and Enisoprost (EP)--with CsA. These investigations dissect the impact of the drug combinations in inhibiting 3H-thymidine incorporation into DNA by normal human peripheral blood lymphocytes activated by mitogens or by alloantigens in mixed lymphocyte culture responses. The median-effect equation was used to analyze the dose-effect relationships of immunosuppressive drugs either alone or in combination. The interactions were quantified by calculation of combination indices (CI). CI values less than 1, greater than 1, and equal to 1 represent synergistic, antagonistic, and additive interactions, respectively. In combination with CsA, 6MP showed modest and Dexa profound synergism, while EP displayed modest and FK506 marked antagonism. These findings confirm the clinical impression of in vivo synergism between CsA and Dexa. They suggest that in vitro analysis of drug interactions may distinguish synergistic drug combinations potentially applicable to clinical practice.

journal_name

Transplantation

journal_title

Transplantation

authors

Vathsala A,Chou TC,Kahan BD

doi

10.1097/00007890-199002000-00044

subject

Has Abstract

pub_date

1990-02-01 00:00:00

pages

463-72

issue

2

eissn

0041-1337

issn

1534-6080

journal_volume

49

pub_type

杂志文章
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    abstract:BACKGROUND:Cardiovascular disease remains epidemic in transplant recipients, despite aggressive treatment of cardiovascular risk factors. Thus, novel risk factors could play a role in the genesis of cardiovascular events in this population. METHODS:We evaluated the impact of early posttransplant anemia on cardiovascul...

    journal_title:Transplantation

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    doi:10.1097/01.TP.0000084872.26360.C5

    authors: Djamali A,Becker YT,Simmons WD,Johnson CA,Premasathian N,Becker BN

    更新日期:2003-09-15 00:00:00

  • Prolongation of second heart transplants in rats.

    abstract::Second clinical kidney grafts often survive longer than first grafts. Using a rat cardiac allograft model, we examined the conditions under which survival of a second graft can be longer than first graft survival. In the BUF-to-LEW combination, following rejection of the first transplant, second cardiac allografts fro...

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    pub_type: 杂志文章

    doi:10.1097/00007890-199210000-00025

    authors: Yanagiya A,Terasaki PI,Iwaki Y,Ho BB,Drinkwater DC,Laks H

    更新日期:1992-10-01 00:00:00

  • Intragraft cytokine profile during human liver allograft rejection.

    abstract::Forty-three human liver allograft biopsies and normal liver were directly analyzed for inflammatory and immunoregulatory cytokine gene expression by polymerase chain reaction (PCR). IL-5 gene expression was predominantly present in biopsies from liver allografts with histopathological evidence of acute rejection. IL-2...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199202010-00035

    authors: Martinez OM,Krams SM,Sterneck M,Villanueva JC,Falco DA,Ferrell LD,Lake J,Roberts JP,Ascher NL

    更新日期:1992-02-01 00:00:00

  • Comparison of arterialized and nonarterialized orthotopic liver transplantation in mice: prowess or relevant model?

    abstract:BACKGROUND:New insights into mechanisms of injury in orthotopic liver transplantation (OLT) often come from experiments in small animal models. Mice are particularly suitable because of the growing availability of gene-altered animals and specific antibodies. A validated model of OLT in mice is not available and, in pa...

    journal_title:Transplantation

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    doi:10.1097/00007890-200211150-00008

    authors: Tian Y,Rüdiger HA,Jochum W,Clavien PA

    更新日期:2002-11-15 00:00:00

  • Prevention and inhibition but not reversion of chronic allograft vasculopathy by FK778.

    abstract:BACKGROUND:This study aimed at investigating the efficacy of the novel immunosuppressant FK778 to prevent the development and progression of chronic allograft vasculopathy (CAV). METHODS:Orthotopic aortic transplantations were performed in the PVG-to-ACI rat model and followed over the course of 120 days. Immunosuppre...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3181673608

    authors: Deuse T,Hoyt G,Koyanagi T,Robbins RC,Schrepfer S

    更新日期:2008-03-27 00:00:00

  • Cytomegalovirus disease is not a major risk factor for ischemic heart disease after renal transplantation.

    abstract:BACKGROUND:It has been suggested that cytomegalovirus infection increases the risk of ischemic heart disease. Both cytomegalovirus and ischemic heart disease are common after renal transplantation, suggesting a possible causal association in this population. METHODS AND PATIENTS:We studied 1004 consecutive renal trans...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200110270-00011

    authors: Hernández D,Hanson E,Kasiske MK,Danielson B,Roel J,Kasiske BL

    更新日期:2001-10-27 00:00:00

  • The successful allotransplantation of neonatal rat islets across multiple combined major and minor histocompatibility barriers.

    abstract::Cultured neonatal rat islets were transplanted across six strain combinations into nonimmunosuppressed allogeneic recipients. Islets were isolated nonenzymatically by an in vitro method and were cultured at 37 degrees C in 5% CO2 in air for 10 days prior to transplant. Transplants to nondiabetic recipients across four...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198712000-00003

    authors: Serie JR,Hegre OD,Eide CR,Weinhaus AJ,Marshall S

    更新日期:1987-12-01 00:00:00

  • Immunohistochemical study of actin binding protein (p55) in the human kidney.

    abstract:BACKGROUND:In clinical transplantation, "passenger" dendritic cells (DCs) in the allograft have been thought to induce allograft rejection. However, the presence of DCs in the normal human kidney is controversial. Most reports have relied on the examination of MHC class I and II antigen expression in combination with D...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199804150-00025

    authors: Sonderbye L,Meehan S,Palsson R,Ahsan N,Ladefoged J,Langhoff E

    更新日期:1998-04-15 00:00:00

  • Transplantation in miniature swine. VII. Evidence for cellular immune mechanisms in hyperacute rejection of renal alografts.

    abstract::Renal allografts were performed in miniature swine that were identical at their major histocompatibility locus and were presensitized by skin grafts from their prospective renal donors. All of these renal grafts were rejected in a hyperacute or markedly accelerated manner compared to the survival of comparable grafts ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: Kirkman RL,Colvin RB,Flye MW,Williams GM,Sachs DH

    更新日期:1979-07-01 00:00:00

  • Technetium-99m sulfur colloid accumulation as a predictor of acute renal transplant rejection.

    abstract::Renal transplantation is the preferred treatment for end-stage renal disease in children. Most transplant failures are due to allograft rejection. To date, only histopathological findings on renal biopsy can establish this diagnosis. Prior to the availability of cyclosporine, technetium-99m sulfur colloid nuclear scan...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199212000-00005

    authors: Massengill SF,Pena DR,Drane WE,Fennell RS,Richard GA

    更新日期:1992-12-01 00:00:00

  • Heart transplantation in diabetic recipients.

    abstract::Preexisting diabetes mellitus (DM) has been regarded as a contraindication to heart transplantation (HT). This prejudice has been based upon concern over increased infection rates and worsening DM with the initiation of prednisone immunosuppression. To better evaluate these suppositions, we reviewed our experience wit...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199002000-00015

    authors: Ladowski JS,Kormos RL,Uretsky BF,Griffith BP,Armitage JM,Hardesty RL

    更新日期:1990-02-01 00:00:00

  • The effect of UVB irradiation on proliferative activity and cell growth potential of cord blood.

    abstract::To determine the degree of graft versus host disease (GVHD) prophylaxis that might be necessary if cord blood (CB) transplantation is more widely applied, we compared human cord blood mononuclear cell (CBMC) and adult peripheral blood mononuclear cell (PBMC) proliferative responses and stimulatory capabilities; to exa...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199408270-00018

    authors: Greenfeld JI,Noizat-Pirenne F,Hardy MA,Oluwole SF,Hesdorffer CA,Preti RA,De Groote D,Franchimont P

    更新日期:1994-08-27 00:00:00

  • Lung rejection occurs in lung transplant recipients with blood chimerism.

    abstract:BACKGROUND:It has been postulated that chimerism after transplantation might promote graft acceptance. In the present study, we prospectively assessed blood chimerism in 10 lung transplant recipients during the first posttransplant year and investigated whether chimerism was associated with an immunologically stable si...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199707150-00030

    authors: Knoop C,Andrien M,Defleur V,Antoine M,de Francquen P,Goldman M,Estenne M

    更新日期:1997-07-15 00:00:00

  • The association of enhancement of renal allograft survival by donor-specific blood transfusion with host MHC-linked inhibition of IgG anti-donor class I alloantibody responses.

    abstract::Donor-specific blood transfusion (DSBT) in animals and humans can either promote subsequent renal graft survival or lead to sensitization and graft rejection. Using a rat renal allograft model, we have examined whether the effects of DSBT on renal allograft outcome and IgG alloantibody responses are linked to the host...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199309000-00033

    authors: Wasowska B,Baldwin WM 3rd,Howell DN,Sanfilippo F

    更新日期:1993-09-01 00:00:00

  • Murine cytomegalovirus infection leads to increased levels of transplant arteriosclerosis in a murine aortic allograft model.

    abstract:INTRODUCTION:Cytomegalovirus infection after heart transplantation is considered as risk factor for the development of transplant arteriosclerosis. Therefore, the aim of this study was to investigate the effect of murine cytomegalovirus (MCMV) as a single risk factor on transplant arteriosclerosis in an experimental ao...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3181e8a699

    authors: Heim C,Abele-Ohl S,Eckl S,Ramsperger-Gleixner M,Mahmoudian S,Weyand M,Stamminger T,Ensminger SM

    更新日期:2010-08-27 00:00:00

  • FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506.

    abstract:BACKGROUND:FK506-binding proteins (FKBP) are immunophilins that interact with the immunosuppressive drugs FK506 and rapamycin. Several FKBP family members such as FKBP12, FKBP12.6, and FKBP51 are expressed in T cells. It has been speculated that these FKBPs are possibly redundant in the immunosuppressant-induced T-cell...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200206150-00023

    authors: Xu X,Su B,Barndt RJ,Chen H,Xin H,Yan G,Chen L,Cheng D,Heitman J,Zhuang Y,Fleischer S,Shou W

    更新日期:2002-06-15 00:00:00

  • Malignant disease in renal transplant patients.

    abstract::The incidence of malignant disease (renal cancer and skin cancer excluded) was analyzed in 934 renal transplant patients from one center, transplanted between 1965 and 1981, and followed through 1983. National Cancer Registry data were used for statistical comparison. Cancers of the lip, vulva, and anus and malignant ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: Blohmé I,Brynger H

    更新日期:1985-01-01 00:00:00

  • Thymocyte/splenocyte-derived CD4+CD25+Treg stimulated by anti-CD200R2 derived dendritic cells suppress mixed leukocyte cultures and skin graft rejection.

    abstract:BACKGROUND:CD200 delivers immunoregulatory signals following engagement of its receptor, CD200R. A family of CD200Rs (CD200R1-4) has been described. Spleen expresses cell surface CD200R1, while bone marrow shows predominantly expression of cell surface CD200R2/R3. We showed that dendritic cell precursors (DCp) cultured...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000214984.65520.50

    authors: Gorczynski RM

    更新日期:2006-04-15 00:00:00

  • Evaluation of Pefabloc as a serine protease inhibitor during human-islet isolation.

    abstract:BACKGROUND:Recent evidence has suggested that inconsistencies in human-islet yields after collagenase digestion are attributed to the activation of endogenous enzymes of the cadaveric donor pancreas. Inhibition of protease activity by Pefabloc (0.4 mM; Roche Biochemicals Inc., Indianapolis, IN) has recently been shown ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.TP.0000046537.47139.CE

    authors: Rose NL,Palcic MM,Helms LM,Lakey JR

    更新日期:2003-02-27 00:00:00

  • Non-major histocompatibility system immunogenetic influences in rat renal allograft survival.

    abstract::H-1-incompatible rat renal allograft survival rates are strongly influenced by the non-major histocompatibility system (MHS) genes. The same H-1 (MHS) incompatibility tested on four different non-MHS backgrounds gave widely differing results ranging from 11 to 60% fractional survival between the best and the poorest (...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197805000-00006

    authors: Paris AM,Bishop C,Festenstein H,Gunther E

    更新日期:1978-05-01 00:00:00

  • Thromboembolism in heart transplantation: role of prothrombin G20210A and factor V Leiden.

    abstract:BACKGROUND:Thromboembolism has been reported as a frequent complication after cardiac transplantation. Many risk factors for thrombosis may explain this, such as metabolic alterations and the use of cyclosporine. In the general population, two single nucleotide polymorphisms (SNPs), factor V Leiden and prothrombin G202...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000170545.42790.6f

    authors: Miriuka SG,Langman LJ,Evrovski J,Miner SE,Kozuszko S,D'Mello N,Delgado DH,Wong BY,Ross HJ,Cole DE

    更新日期:2005-09-15 00:00:00

  • Antileukocyte antibody in postpartum and renal transplant subjects. A comparison of capillary agglutination and lymphocytotoxicity reactions.

    abstract::Sera were obtained from 48 gravida II prenatal and 211 multiparous nonpregnant females and examined for leukocyte antibodies comparing a standard lymphocytotoxicity (CY) test with capillary agglutination (CA). Antibody was detected in 41% of the samples in both groups but only CA tests were positive with approximately...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197602000-00001

    authors: Thompson JS,Jackson D,Greazel NA,Parmely MJ,Severson CD

    更新日期:1976-02-01 00:00:00

  • Defining delayed graft function after renal transplantation: simplest is best.

    abstract:BACKGROUND:Delayed graft function (DGF) after renal transplantation can be diagnosed according to several different definitions, complicating comparison between studies that use DGF as an endpoint. This is a particular problem after transplantation with kidneys from donation after circulatory death (DCD) kidneys, becau...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3182a19348

    authors: Mallon DH,Summers DM,Bradley JA,Pettigrew GJ

    更新日期:2013-11-27 00:00:00

  • Successful renovascular reconstruction for renal allografts with multiple renal arteries.

    abstract:BACKGROUND:Kidney grafts with multiple renal arteries have been considered a relative contraindication because of the increased risk of complications. In the present study, we retrospectively reviewed multiple renal artery reconstruction in kidney transplantation to elucidate the usefulness of these grafts. METHODS:Fr...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.TP.0000054461.57565.18

    authors: Makiyama K,Tanabe K,Ishida H,Tokumoto T,Shimmura H,Omoto K,Toma H

    更新日期:2003-03-27 00:00:00

  • Increasing the donor pool using en bloc pediatric kidneys for transplant.

    abstract:OBJECTIVES:En bloc pediatric kidney transplants (EBPKT) are still a subject of controversy. The aim of this study was to determine whether acceptable long-term graft survival and function can be achieved in EBPKT compared with the transplant of single, cadaveric, adult donor kidneys. METHODS:A retrospective review was...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.TP.0000090395.98045.09

    authors: Sánchez-Fructuoso AI,Prats D,Pérez-Contín MJ,Marques M,Torrente J,Conesa J,Grimalt J,Del Rio F,Núñez JR,Barrientos A

    更新日期:2003-10-27 00:00:00

  • Effects of protein-calorie restriction on the immune response to skin allografts in the rat.

    abstract::The effect of protein depletion on immune responsiveness was examined using a skin allograft model. Protein depletion was induced in adult Fischer (F344) male rats by the ad libitum provision of a 5% protein diet. Total serum protein, total body weight, total body nitrogen, and total body lipid were all markedly decre...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198009000-00012

    authors: Austin EH,Brennan MF,Rosenberg SA

    更新日期:1980-09-01 00:00:00

  • Efficacy of RS-61443 in reversing acute rejection in a rat model of hindlimb allotransplantation.

    abstract::The requirement for effective, minimally toxic immunosuppression remains a major obstacle to performing human composite tissue allotransplantation. The skin component of composite tissue (e.g., limb) allografts is especially antigenic, necessitating toxic immunosuppressant doses to prevent or reverse acute rejection. ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199402150-00020

    authors: van den Helder TB,Benhaim P,Anthony JP,McCalmont TH,Mathes SJ

    更新日期:1994-02-01 00:00:00

  • Mitotic behaviour and proliferative metabolism in allogenic rat kidney transplants in the first 6 days after recirculation.

    abstract::Comparative experiments were performed on 41 allogenic rat kidney transplants to determine the mitotic behaviour and proliferative metabolism (application of 3H-thymidine) in the first 6 days after recirculation. Three days after transplantation, DNA synthesis in the tubular epithelial cells of the cortex and the medu...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197807010-00003

    authors: Lauschke H

    更新日期:1978-07-01 00:00:00

  • Anti-inflammatory effect of transforming growth factor-beta1 in myoblast transplantation.

    abstract:BACKGROUND:The inflammatory reaction that occurs during the 5 days after transplantation led at 3 days to the death of 70% of injected myoblasts. Use of anti-inflammatory agents appeared to be a possible way to increase myoblast survival. The application of gene transfer techniques to cell transplantation offers the po...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199803270-00005

    authors: Merly F,Huard C,Asselin I,Robbins PD,Tremblay JP

    更新日期:1998-03-27 00:00:00

  • Mannitol infusion within 15 min of cross-clamp improves living donor kidney preservation.

    abstract:BACKGROUND:Optical coherence tomography (OCT) revealed that cells lining proximal convoluted tubules of living donor kidneys (LDKs) procured by laparoscopic procedures were very swollen in response to the brief period of ischemia experienced between the time of arterial vessel clamping and flushing the excised kidney w...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000000154

    authors: Andrews PM,Cooper M,Verbesey J,Ghasemian S,Rogalsky D,Moody P,Chen A,Alexandrov P,Wang HW,Chen Y

    更新日期:2014-10-27 00:00:00