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
  • Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: a controlled trial in liver transplant recipients.

    abstract:BACKGROUND:Early enteral nutrition with solutions containing prebiotics (fiber) and probiotics (Lactobacillus) is suggested to reduce bacterial translocation and minimize the incidence of infections after liver transplantation. METHODS:In a prospective, randomized placebo-controlled trial consisting of 95 patients, we...

    journal_title:Transplantation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00007890-200207150-00021

    authors: Rayes N,Seehofer D,Hansen S,Boucsein K,Müller AR,Serke S,Bengmark S,Neuhaus P

    更新日期:2002-07-15 00:00:00

  • A prospective study of human herpesvirus type 6 detected by polymerase chain reaction after liver transplantation.

    abstract::Human herpesvirus type 6 (HHV-6) causes roseola infantum (exanthema subitum) upon primary infection in young children. Thereafter it persists lifelong in the organism. Like other herpesviruses, HHV-6 can be reactivated in periods of immunosuppression - e.g., after organ transplantation. In order to study the incidence...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199602270-00027

    authors: Schmidt CA,Wilbron F,Weiss K,Brinkmann V,Oettle H,Lohmann R,Langrehr JM,Neuhaus P,Siegert W

    更新日期:1996-02-27 00:00:00

  • Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. V. Dependence of CD4+ suppressor cells on the presence of alloantigen and cytokines, including interleukin 2.

    abstract::CD4+ cells from CsA-treated DA rats with long-surviving PVG heart allografts specifically suppress the capacity of naive CD4+ cells to restore allograft rejection in irradiated DA rats, but have normal donor-specific alloreactivity in MLC. CD4+ suppressor cells from CsA-treated DA rats cultured for 3 days against eith...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199302000-00027

    authors: Pearce NW,Spinelli A,Gurley KE,Hall BM

    更新日期:1993-02-01 00:00:00

  • Resolution and relapse of osteopetrosis in mice transplanted with myeloid tissue of variable histocompatibility.

    abstract::Osteopetrotic microphthalmic mice (mi/mi) were treated by injections of suspensions of myeloid tissue, newborns i.p., and weanlings i.v. Donated syngeneic material effected permanent cure of oteopetrosis provided that the dose was large enough (10(8) cells of bone marrow). H-2-compatible allogeneic bone marrow was ini...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197910000-00004

    authors: Nisbet NW,Menage J,Loutit JF

    更新日期:1979-10-01 00:00:00

  • Venous thromboembolic complications after kidney and kidney-pancreas transplantation: a multivariate analysis.

    abstract:BACKGROUND:We reviewed the incidence of and risk factors for venous thromboembolic complications in our population of kidney (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients. METHODS:Information was collected retrospectively from a database on 1833 KTx and 276 SPK recipients who underwent transplant ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199801270-00015

    authors: Humar A,Johnson EM,Gillingham KJ,Sutherland DE,Payne WD,Dunn DL,Wrenshall LE,Najarian JS,Gruessner RW,Matas AJ

    更新日期:1998-01-27 00:00:00

  • Interleukin-6, A Cytokine Critical to Mediation of Inflammation, Autoimmunity and Allograft Rejection: Therapeutic Implications of IL-6 Receptor Blockade.

    abstract::The success of kidney transplants is limited by the lack of robust improvements in long-term survival. It is now recognized that alloimmune responses are responsible for the majority of allograft failures. Development of novel therapies to decrease allosensitization is critical. The lack of new drug development in kid...

    journal_title:Transplantation

    pub_type: 杂志文章,评审

    doi:10.1097/TP.0000000000001452

    authors: Jordan SC,Choi J,Kim I,Wu G,Toyoda M,Shin B,Vo A

    更新日期:2017-01-01 00:00:00

  • Crossreactivity between human and canine Ia antigens using a mouse monoclonal antibody (CIA).

    abstract::A mouse monoclonal antibody (CIA) produced against human Ia antigens that reacts with 20-30% of human peripheral blood lymphocytes was found to react with more than 90% of dog lymphocytes. Less than 41% of the Ia-positive dog lymphocytes expressed surface immunoglobulins. Immunoprecipitation studies with 125I-labeled ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198308000-00016

    authors: Iwaki Y,Terasaki PI,Kinukawa T,Thai TH,Root T,Billing R

    更新日期:1983-08-01 00:00:00

  • Reduced human IgG anti-ATGAM antibody formation in renal transplant recipients receiving mycophenolate mofetil.

    abstract::Exposure to the equine-derived polyclonal antithymocyte preparation, ATGAM, frequently elicits human anti-ATGAM antibody formation. The influence of concomitant immunosuppressants on this antiantibody response has not been established. We therefore evaluated IgG antibody formation to ATGAM in 47 patients receiving ATG...

    journal_title:Transplantation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00007890-199560120-00001

    authors: Kimball JA,Pescovitz MD,Book BK,Norman DJ

    更新日期:1995-12-27 00:00:00

  • Studies into the transplantation biology of ultraviolet light-induced tumors.

    abstract::The majority of skin tumors induced in mice by ultraviolet (UV) light are rejected when implanted into normal syngeneic recipients. Subcarcinogenic levels of UV light exposure render the normally resistant mice susceptible to tumor challenge. The immunoregulatory effect of UV light appears to be additive, since the gr...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197704000-00008

    authors: Daynes RA,Spellman CW,Woodward JG,Stewart DA

    更新日期:1977-04-01 00:00:00

  • The immediate function of the kidney after 24-to 72-hr preservation. Hypothermic storage versus mechanical perfusion.

    abstract::Seventy-two dog kidneys were stored under hypothermia as described by Collins and Sacks between 24 and 72 hr and then transplanted. The immediate function of the kidneys was measured by p-aminohippuric acid and inulin clearances. Twenty-four hr proved to be the maximum safe preservation time with both methods. The imm...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197705000-00009

    authors: Grundmann R,Strümper R,Eichmann J,Pichlmaier H

    更新日期:1977-05-01 00:00:00

  • The regulatory/cytotoxic graft-infiltrating T cells differentiate renal allograft borderline change from acute rejection.

    abstract::The interpretation of cellular infiltrate from renal transplant recipients with borderline (BL) changes is still a challenging problem. To analyze the immune phenotype of such infiltrate, we quantified the mRNA expression of Foxp3 and interleukinL-10 and granzyme B (GB) in 15 kidney biopsies with BL changes. Controls ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000248884.71946.19

    authors: Grimbert P,Mansour H,Desvaux D,Roudot-Thoraval F,Audard V,Dahan K,Berrehar F,Dehoulle-Poillet C,Farcet JP,Lang P,Le Gouvello S

    更新日期:2007-02-15 00:00:00

  • Induction of donor-specific T-cell hyporesponsiveness using dexamethasone-treated dendritic cells in two fully mismatched rat kidney transplantation models.

    abstract:BACKGROUND:Dendritic cells (DC) can exert powerful immune stimulatory as well as regulatory functions and are therefore important tools for therapeutic strategies. Dexamethasone (Dex) was previously shown to inhibit DC maturation and to induce regulatory properties both in vitro and in vivo. Here, we investigated the i...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31818a6682

    authors: Stax AM,Gelderman KA,Schlagwein N,Essers MC,Kamerling SW,Woltman AM,van Kooten C

    更新日期:2008-11-15 00:00:00

  • Zoom endoscopic evaluation of rejection in living-related small bowel transplantation.

    abstract:BACKGROUND:This study evaluated zoom endoscopic findings according to four components in comparison with the histologic findings of acute cellular rejection (ACR) in a living-related small bowel transplantation (SBTx) patient. METHODS:A 16-year-old boy with microvillus inclusion disease underwent SBTx with a 150-cm-lo...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200202270-00013

    authors: Sasaki T,Hasegawa T,Nakai H,Kimura T,Okada A,Musiake S,Doi R

    更新日期:2002-02-27 00:00:00

  • Comparative analysis of the DST and Imuran-plus-DST protocols for live donor renal transplantation.

    abstract::We have done a comparative analysis of two consecutive clinical trials at our center: the first in 56 patients who received blood transfusions from their prospective donors (DST group), and the second in 36 patients who received such transfusions while they were taking Imuran in an attempt to reduce the incidence of s...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198336060-00009

    authors: Glass NR,Miller DT,Sollinger HW,Belzer FO

    更新日期:1983-12-01 00:00:00

  • Critical influence of natural regulatory CD25+ T cells on the fate of allografts in the absence of immunosuppression.

    abstract:BACKGROUND:Allografts are occasionally accepted in the absence of immunosuppression. Because naturally occurring CD4(+)CD25(+) regulatory T cells (natural CD25(+) Treg cells) have been shown to inhibit allograft rejection, we investigated their influence on the outcome of allografts in nonimmunosuppressed mouse recipie...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000155179.61445.78

    authors: Benghiat FS,Graca L,Braun MY,Detienne S,Moore F,Buonocore S,Flamand V,Waldmann H,Goldman M,Le Moine A

    更新日期:2005-03-27 00:00:00

  • Quantitative serological analysis of a rabbit anti-rat lymphocyte serum and preliminary biochemical characterisation of the major antigen recognised.

    abstract::Rabbit antisera to rat thoracic duct lymphocytes were examined by absorption analysis with quantitative radioimmunoassays to determine the tissue distribution of the antigens recognised and the amount of antibody against different specificities. Seven of eight sera were remarkably specific for leucocytes and one serum...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197704000-00009

    authors: Fabre JW,Williams AF

    更新日期:1977-04-01 00:00:00

  • Defining a Willingness-to-transplant Threshold in an Era of Organ Scarcity: Simultaneous Liver-kidney Transplant as a Case Example.

    abstract:BACKGROUND:Organ scarcity continues in solid organ transplantation, such that the availability of organs limits the number of people able to benefit from transplantation. Medical advancements in managing end-stage organ disease have led to an increasing demand for multiorgan transplant, wherein a patient with multiorga...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000002788

    authors: Cheng XS,Goldhaber-Fiebert J,Tan JC,Chertow GM,Kim WR,Wall AE

    更新日期:2020-02-01 00:00:00

  • Successful Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Ledipasvir in Renal Transplant Recipients.

    abstract:BACKGROUND:Treatment of chronic hepatitis C virus (HCV) infection after renal allograft transplantation has been an obstacle because of contraindications associated with IFN-based therapies. Direct-acting antiviral agents are highly efficient treatment options that do not require IFN and may not require ribavirin. Ther...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000001414

    authors: Eisenberger U,Guberina H,Willuweit K,Bienholz A,Kribben A,Gerken G,Witzke O,Herzer K

    更新日期:2017-05-01 00:00:00

  • mTOR Inhibition Role in Cellular Mechanisms.

    abstract::The mammalian target of rapamycin inhibitors (mTOR-I), drugs widely used in transplant medicine and oncology, exert their function by inhibiting a serine/threonine kinase with a pivotal role in cellular metabolism and in a wide range of eukaryotic biological/cellular functions and signaling networks. Additionally, as ...

    journal_title:Transplantation

    pub_type: 杂志文章,评审

    doi:10.1097/TP.0000000000001806

    authors: Zaza G,Granata S,Caletti C,Signorini L,Stallone G,Lupo A

    更新日期:2018-02-01 00:00:00

  • Pancreatitis following liver transplantation.

    abstract::Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B-related liver disease. To either confirm this clinical impression or refute it,...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198806000-00012

    authors: Alexander JA,Demetrius AJ,Gavaler JS,Makowka L,Starzl TE,Van Thiel DH

    更新日期:1988-06-01 00:00:00

  • Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection.

    abstract:BACKGROUND:Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. We sought to determine whether CMV prophylaxis administered for three months after heart transplant would improve patient outcomes. METHODS:This prospective cohort study...

    journal_title:Transplantation

    pub_type: 临床试验,杂志文章

    doi:10.1097/01.tp.0000229039.87735.76

    authors: Potena L,Holweg CT,Chin C,Luikart H,Weisshaar D,Narasimhan B,Fearon WF,Lewis DB,Cooke JP,Mocarski ES,Valantine HA

    更新日期:2006-08-15 00:00:00

  • Increased infections in liver transplant recipients with recurrent hepatitis C virus hepatitis.

    abstract::Infectious complications in patients with recurrent hepatitis C virus (HCV) hepatitis after liver transplantation were prospectively assessed and compared with those of all other liver transplant recipients without HCV hepatitis operated on during the same period. Major infections occurred in 64% (14/22) of the patien...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199602150-00014

    authors: Singh N,Gayowski T,Wagener MM,Marino IR

    更新日期:1996-02-15 00:00:00

  • Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study.

    abstract:BACKGROUND:Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain, functional loss, and disability. Osteoarthritis often becomes chronic, and conventional treatments have demonstrated only modest clinical benefits without lesion reversal. Cell-based therapies have shown encouraging result...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e318291a2da

    authors: Orozco L,Munar A,Soler R,Alberca M,Soler F,Huguet M,Sentís J,Sánchez A,García-Sancho J

    更新日期:2013-06-27 00:00:00

  • The vascular endothelial cell antigen system.

    abstract::Vascular endothelial cells (VEC) are clearly immunogenic and express antigens unique to vascular endothelial cells. The observation that peripheral blood monocytes also express this VEC antigen system made prospective testing feasible. Preformed antibody to the VEC/monocyte antigen system of the donor usually leads to...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198503000-00016

    authors: Cerilli J,Brasile L,Galouzis T,Lempert N,Clarke J

    更新日期:1985-03-01 00:00:00

  • A computerized system for the selection of organ transplant recipients.

    abstract::The Southeastern Regional Organ Procurement Program has developed a computerized system for the selection of organ transplant recipients. This system has proven to be a useful method for the rapid selection of histocompatible recipients for organ transplants from a large pool of potential recipients in a wide geograp...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197501000-00005

    authors: Stulting RD,Ward FE

    更新日期:1975-01-01 00:00:00

  • Attenuating Ischemia-Reperfusion Injury in Kidney Transplantation by Perfusing Donor Organs With siRNA Cocktail Solution.

    abstract:BACKGROUND:Ischemia-reperfusion (I/R) injury is the major cause of delayed renal graft function in kidney transplantation. To date, there are no effective therapeutic approaches for preventing I/R injury. We previously reported that treatment of animals with small interference RNA (siRNA) would prevent warm I/R injury ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000000960

    authors: Zheng X,Zang G,Jiang J,He W,Johnston NJ,Ling H,Chen R,Zhang X,Liu Y,Haig A,Luke P,Jevnikar AM,Min WP

    更新日期:2016-04-01 00:00:00

  • Fifty-percent partial liver transplantation in the rat.

    abstract::Reduced-size liver transplantation in the rat has been useful in the study of hepatic regeneration. We describe a modified technique for partial liver transplantation in the rat using a 50% reduced-size graft. Male Lewis rats (RT1(1)), weighing 250 to 280 g, were used as donors and recipients. The harvested donor live...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199607270-00023

    authors: Omura T,Ascher NL,Emond JC

    更新日期:1996-07-27 00:00:00

  • Posttransplant diabetes mellitus and atherosclerotic events in renal transplant recipients: a prospective study.

    abstract:BACKGROUND:Posttransplant diabetes mellitus (PTDM) is a frequent complication in renal-transplant recipients (RTRs). We conducted a prospective study to assess the potential role of PTDM in the development of atherosclerotic events (AE) in RTRs. METHODS:Three hundred fifty-seven consecutive RTRs were enrolled in this ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000151799.98612.eb

    authors: Ducloux D,Kazory A,Chalopin JM

    更新日期:2005-02-27 00:00:00

  • Should All Status 1A Patients Be Prioritized Over High MELD Patients? Concept of Risk Stratification in Extremely Ill Liver Transplant Recipients.

    abstract:BACKGROUND:Status 1A patients are prioritized over liver disease patients regardless of Model for End-stage Liver Disease (MELD) score. We aimed to identify groups with high waitlist mortality in Status 1A and MELD ≥40 patients to determine who would most benefit from transplantation. METHODS:Data on patients listed a...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000002651

    authors: Safwan M,Nwagu U,Collins K,Abouljoud M,Nagai S

    更新日期:2019-10-01 00:00:00

  • Anti-immunoglobulin as an adjunct in producing long-term antigen-specific allograft survival. Organ localization of immune complexes.

    abstract::Heterologous anti-immunoglobulin is a potent immunosuppressive agent that prolongs H-2- and H-3-incompatible skin graft survival. In conjunction with antithymocyte serum, anti-immunoglobulin promotes greater graft life than either antiserum used alone, without evidence of toxicity to recipient animals. Combination tre...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197711000-00007

    authors: Constantian MB,Couser WG,Mannick JA

    更新日期:1977-11-01 00:00:00