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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Chemical Compound Review

AC1L9392     6-(3-methyl-5-nitro-imidazol- 4-yl)sulfanyl...

Synonyms:
 
 
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Disease relevance of Imuran

  • In particular, the decrease in STF and SSRFC levels is ascribed to the replication-competent (Friend-murine leukemia virus) component of Friend leukemia virus complex, whereas the decrease in AZ sensitivity of splenocytes and the increase of SSRFCs are ascribed to the defective spleen focus-forming virus component of the complex [1].
  • CONCLUSION: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen [2].
  • Lymphoproliferative disorders were diagnosed in one AZA (0.6%), two MMF 2 g (1.2%), and three MMF 3 g (1.8%) patients [3].
  • A Cox proportional hazard model accounting for the above mentioned covariates isolated MMF versus AZA as a significant risk factor for the occurrence of serious infectious events (all: P<0.01; cytomegalovirus, fungal: P<0.01) [4].
  • CONCLUSIONS: This report suggests that AZA is a more potent antiviral than MPA for Flaviviridae and may exert a specific antiviral effect on HCV [5].
 

High impact information on Imuran

  • Abnormal cytolytic responses in SLE could not be attributed to the patient's sex, race, age, disease activity, or antirheumatic medications (including corticosteroids and cytotoxics), although both SLE and RD patients taking azathioprine (AZA) manifested lower responses than did corresponding patients not taking AZA [6].
  • We updated 2 metaanalyses of published clinical trials, by adding trials published through 1990 and trials of azathioprine (AZA) [7].
  • Three-yr death-censored graft survival for Caucasians was 90.1 versus 86.4% (P<0.001) for MMF and AZA, respectively [8].
  • Since transplantation, the median follow-up was 18 years in AZA-treated and 13 years in CsA-treated patients [9].
  • The present study compares MAZA to the widely recognized drugs AZA, 6-MP, and 6-TG with respect to the ability of being transported across cell membranes [10].
 

Chemical compound and disease context of Imuran

 

Biological context of Imuran

  • The effect of AZA on a HCV replicon was at least as large as that of ribavirin [5].
  • Studies of the kinetics of anti-donor MLC responses of PBL obtained from patients before and after DST + AZA treatment revealed shifts in the magnitude and timing of antidonor MLC response [15].
  • RESULTS: Patients receiving MMF had an average immunocompetence level of 12+/-23, compared with 39.7+/-65 and 25.5+/-42 for those receiving AZA or neither AZA nor MMF, respectively [16].
  • The spontaneous remission of this MDS with monosomy 7, which is usually associated with a particularly poor prognosis, could be due to the recovery of a better immunosurveillance following the withdrawal of AZA [13].
  • The results from Stanford also reveal an important difference between everolimus and AZA with regard to intimal thickening and the incidence of abnormal left ventricular ejection fraction (LVEF), suggesting that everolimus may improve left ventricular function [17].
 

Anatomical context of Imuran

  • In both the Aza and CsA group, an increase in DR+ peripheral lymphocytes correlated with positive staining of the renal tubular cells for HLA-DR antigens (P less than 0.001) [18].
  • However, in the AZA group, both the number of NK cells and their cytotoxic activity were significantly (<0.002) lower compared to the values in the CsA group [19].
  • In the Aza group, clinical rejection episodes correlated with an increased percentage of DR+ peripheral lymphocytes (P = 0.0005), and the expression of DR antigens on graft epithelial cells (P less than 0.001) [18].
  • RESULTS: Drug concentrations (mg/L) causing a 50% inhibition of fibroblast proliferation were mPRED 4; CsA 20; FK506 0.3; AZA 7; MMF 0.3; and RAD 0.0006 [20].
  • Both myeloperoxidase activity and the number of neutrophils accumulating in the liver 24 hours after reperfusion in animals treated with AZA, CsA, FK506, and RPM were significantly lower than in untreated animals [21].
 

Associations of Imuran with other chemical compounds

 

Gene context of Imuran

  • The enhanced production of IL-10 detected before or at relapse with AZA and IFN-beta 1 a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions [26].
  • Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon (IFN) beta 1 a, or corticosteroids (CST) [26].
  • RESULTS: With regard to inflammation, significantly lower values were found for high-sensitive C-reactive protein (CRP) in the MMF group (AZA 1.8 +/- 1.2 mg/liter. vs MMF 1.0 +/- 4.1 mg/liter, p = 0.02) [27].
  • Renal transplant recipients who are treated with AZA and who exhibit an increase in TPMT activity from the time of transplantation experience fewer episodes of active rejection [28].
  • Cancer incidence associated with AZA versus CYA, CYA versus TAC, and AZA versus mycophenolate mofetil (MMF) is compared in both transplant center and registry reports including new, unreported Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from 1998 to 2003 [29].
 

Analytical, diagnostic and therapeutic context of Imuran

  • This decrease in risk was greater in Caucasian transplant recipients (MMF vs. AZA: 16% vs. 46%, RR=0.35, P < 0.001) than in African-American patients (32% vs. 36%, RR=0.88, P=0.6) [30].
  • Plasma was obtained from patients prior to AZA and DST (to), 2-6 weeks after the final transfusion but immediately prior to transplant (tt), and 6-12 weeks after renal transplantation and initiation of standard posttransplant immunosuppressive therapy (tx) [31].
  • Our purpose was to identify humoral factors induced by donor-specific transfusion (DST) plus azathioprine (AZA) that correlate with improved renal allograft survival (92% at 3-34 months posttransplantation) in a group of 24 DST patients [31].
  • These patients were compared with a historic control group (n=54) receiving azathioprine (AZA) instead of MMF [32].
  • Her serum remained negative for antidonor antibodies both by standard cytotoxicity assay and by immunofluorescence flow cytometry after DST + AZA treatment, and she experienced no acute rejection episodes following donor kidney transplantation [33].

References

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  2. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial. Houssiau, F.A., Vasconcelos, C., D'Cruz, D., Sebastiani, G.D., de Ramon Garrido, E., Danieli, M.G., Abramovicz, D., Blockmans, D., Mathieu, A., Direskeneli, H., Galeazzi, M., Gül, A., Levy, Y., Petera, P., Popovic, R., Petrovic, R., Sinico, R.A., Cattaneo, R., Font, J., Depresseux, G., Cosyns, J.P., Cervera, R. Arthritis Rheum. (2004) [Pubmed]
  3. A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation: results at three years. Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. Mathew, T.H. Transplantation (1998) [Pubmed]
  4. Infectious complications in geriatric renal transplant patients: comparison of two immunosuppressive protocols. Meier-Kriesche, H.U., Friedman, G., Jacobs, M., Mulgaonkar, S., Vaghela, M., Kaplan, B. Transplantation (1999) [Pubmed]
  5. Effect of antimetabolite immunosuppressants on Flaviviridae, including hepatitis C virus. Stangl, J.R., Carroll, K.L., Illichmann, M., Striker, R. Transplantation (2004) [Pubmed]
  6. Impaired polyclonal T cell cytolytic activity. A possible risk factor for systemic lupus erythematosus. Stohl, W. Arthritis Rheum. (1995) [Pubmed]
  7. Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials. Felson, D.T., Anderson, J.J., Meenan, R.F. Arthritis Rheum. (1992) [Pubmed]
  8. Effect of mycophenolate mofetil on long-term outcomes in African american renal transplant recipients. Meier-Kriesche, H.U., Ojo, A.O., Leichtman, A.B., Punch, J.D., Hanson, J.A., Cibrik, D.M., Kaplan, B. J. Am. Soc. Nephrol. (2000) [Pubmed]
  9. Natural history of hepatitis B and C in renal allograft recipients. Aroldi, A., Lampertico, P., Montagnino, G., Passerini, P., Villa, M., Campise, M.R., Lunghi, G., Tarantino, A., Cesana, B.M., Messa, P., Ponticelli, C. Transplantation (2005) [Pubmed]
  10. Modeling of purine derivatives transport across cell membranes based on their partition coefficient determination and quantum chemical calculations. Hoffmann, M., Chrzanowska, M., Hermann, T., Rychlewski, J. J. Med. Chem. (2005) [Pubmed]
  11. Effect of different immunosuppressive agents on acute pancreatitis: a comparative study in an improved animal model. Foitzik, T., Forgacs, B., Ryschich, E., Hotz, H., Gebhardt, M.M., Buhr, H.J., Klar, E. Transplantation (1998) [Pubmed]
  12. Mercaptopurine metabolite results in clinical gastroenterology practice. Bloomfeld, R.S., Onken, J.E. Aliment. Pharmacol. Ther. (2003) [Pubmed]
  13. Spontaneous remission in a patient with therapy-related myelodysplastic syndrome (t-MDS) with monosomy 7. Renneboog, B., Hansen, V., Heimann, P., De Mulder, A., Jannsen, F., Ferster, A. Br. J. Haematol. (1996) [Pubmed]
  14. A study of maternal lymphoid organs and the progeny following treatment with immunomodulating agents during pregnancy. Scott, J.R., Feldbush, T.L., Covault, J.M. Clin. Exp. Immunol. (1977) [Pubmed]
  15. Improved renal allograft survival following donor-specific transfusions. II. In vitro correlates of early (DST-type) rejection episodes. Burlingham, W.J., Grailer, A., Sparks-Mackety, E.M., Sondel, P.M., Sollinger, H.W. Transplantation (1987) [Pubmed]
  16. Measurement of mycophenolate mofetil effect in transplant recipients. Ogawa, N., Nagashima, N., Nakamura, M., Shalabi, A., Maley, W.R., Burdick, J.F. Transplantation (2001) [Pubmed]
  17. Prevention of cardiac allograft vasculopathy with Certican (everolimus): the Stanford University experience within the Certican Phase III clinical trial. Valantine, H. J. Heart Lung Transplant. (2005) [Pubmed]
  18. Expression of HLA-DR antigens on peripheral blood T lymphocytes and renal graft tubular epithelial cells in association with rejection. Henny, F.C., Weening, J.J., Baldwin, W.M., Oljans, P.J., Tanke, H.J., van Es, L.A., Paul, L.C. Transplantation (1986) [Pubmed]
  19. Reassuring effect of pravastatin on natural killer cell activity in stable renal transplant patients. Vaessen, L.M., van Miert, P.P., van Gelder, T., Ijzermans, J.N., Weimar, W. Transplantation (2001) [Pubmed]
  20. Everolimus and mycophenolate mofetil are potent inhibitors of fibroblast proliferation after lung transplantation. Azzola, A., Havryk, A., Chhajed, P., Hostettler, K., Black, J., Johnson, P., Roth, M., Glanville, A., Tamm, M. Transplantation (2004) [Pubmed]
  21. Immunosuppressants decrease neutrophil chemoattractant and attenuate ischemia/reperfusion injury of the liver in rats. Matsuda, T., Yamaguchi, Y., Matsumura, F., Akizuki, E., Okabe, K., Liang, J., Ohshiro, H., Ichiguchi, O., Yamada, S., Mori, K., Ogawa, M. The Journal of trauma. (1998) [Pubmed]
  22. A four-year experience with donor blood transfusion protocols for living-donor renal transplantation. Glass, N.R., Miller, D.T., Sollinger, H.W., Belzer, F.O. Transplantation (1985) [Pubmed]
  23. Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation. van Besouw, N.M., van der Mast, B.J., de Kuiper, P., Smak regoor, P.J., Vaessen, L.M., Ijzermans, J.N., van Gelder, T., Weimar, W. Clin. Exp. Immunol. (2002) [Pubmed]
  24. A three or more drug combination as effective therapy for moderate or severe chronic graft-versus-host disease. Gaziev, D., Lucarelli, G., Polchi, P., Angelucci, E., Galimberti, M., Giardini, C., Baronciani, D., Erer, B., Sodani, P. Bone Marrow Transplant. (2001) [Pubmed]
  25. Renal transplantation in a case of acute intermittent porphyria. Warholm, C., Wilczek, H. Journal of clinical pharmacology. (2003) [Pubmed]
  26. Assessing multiple sclerosis activity: is the in vitro production of tumor necrosis factor-alpha, interleukins 2, 6, 4, and 10, and immunoglobulin G of value? Schluep, M., van Melle, G., Henry, H., Städler, C., Roth-Wicky, B., Magistretti, P.J. J. Neurol. (1999) [Pubmed]
  27. Mycophenolate mofetil for secondary prevention of cardiac allograft vasculopathy: influence on inflammation and progression of intimal hyperplasia. Pethig, K., Heublein, B., Wahlers, T., Dannenberg, O., Oppelt, P., Haverich, A. J. Heart Lung Transplant. (2004) [Pubmed]
  28. The monitoring of immunosuppressive drugs: a pharmacodynamic approach. Yatscoff, R.W., Aspeslet, L.J. Therapeutic drug monitoring. (1998) [Pubmed]
  29. Post-transplant de novo malignancies in renal transplant recipients: the past and present. Kauffman, H.M., Cherikh, W.S., McBride, M.A., Cheng, Y., Hanto, D.W. Transpl. Int. (2006) [Pubmed]
  30. Mycophenolate mofetil reduces the risk of acute rejection less in African-American than in Caucasian kidney recipients. Schweitzer, E.J., Yoon, S., Fink, J., Wiland, A., Anderson, L., Kuo, P.C., Lim, J.W., Johnson, L.B., Farney, A.C., Weir, M.R., Bartlett, S.T. Transplantation (1998) [Pubmed]
  31. Improved renal allograft survival following donor-specific transfusions. I. Induction of antibodies that inhibit primary antidonor MLC response. Burlingham, W.J., Sparks, E.M., Sondel, P.M., Glass, N.R., Belzer, F.O., Sollinger, H.W. Transplantation (1985) [Pubmed]
  32. Pediatric renal transplantation with mycophenolate mofetil-based immunosuppression without induction: results after three years. Jungraithmayr, T., Staskewitz, A., Kirste, G., Böswald, M., Bulla, M., Burghard, R., Dippell, J., Greiner, C., Helmchen, U., Klare, B., Klaus, G., Leichter, H.E., Mihatsch, M.J., Michalk, D.V., Misselwitz, J., Plank, C., Querfeld, U., Weber, L.T., Wiesel, M., Tönshoff, B., Zimmerhackl, L.B. Transplantation (2003) [Pubmed]
  33. Induction of antiidiotypic antibodies to donor HLA-A2 following blood transfusions in a highly sensitized HLA-A2+ recipient. Burlingham, W.J., Pan, M.H., Mason, B., Ceman, S., Sollinger, H.W. Transplantation (1988) [Pubmed]
 
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