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https://www.readbyqxmd.com/read/29149986/effects-of-cyclosporine-tacrolimus-and-rapamycin-on-osteoblasts
#1
M Martín-Fernández, M Rubert, M Montero, C de la Piedra
PURPOSE: One factor that can contribute to severe bone loss after transplantation is the direct action of immunosuppressants on bone cells. The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on the release of three local factors directly implicated in bone-remodeling regulation and apoptosis of human osteoblasts: interleukin (IL)-6, osteoprotegerin, and receptor activator of nuclear factor κβ (RANKL). BASIC PROCEDURES: Human osteoblasts were obtained from five different patients who underwent orthopedic surgery...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149976/clinical-challenges-of-tacrolimus-for-maintenance-immunosuppression-post-lung-transplantation
#2
S Ivulich, M Dooley, C Kirkpatrick, G Snell
Lung transplantation (LTx) is a successful treatment option for end-stage lung disease, and immunosuppressant regimens, utilized to prevent rejection of the transplanted graft, are paramount to maintaining long-term graft survival. Immunosuppression can be classified as induction, maintenance, and antirejection therapy. This article focuses on maintenance immunosuppression that includes a combination of a calcineurin inhibitor (CNI), cell cycle inhibitor, and corticosteroid. CNIs remain the cornerstone of immunosuppression following LTx, and tacrolimus is now the preferred CNI, based on a better adverse effect profile and some limited evidence for enhanced efficacy...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149962/impact-of-acute-infection-requiring-hospitalization-on-tacrolimus-blood-levels-in-kidney-transplant-recipients
#3
C Percy, Z Hassoun, M Mourad, M De Meyer, C Beguin, M Jadoul, E Goffin, P Wallemacq, N Kanaan
BACKGROUND: Tacrolimus is metabolized by members of the cytochrome p450 3A subfamily, and its bioavailability depends also on P-glycoprotein. We have observed that some patients admitted for infection presented with increased tacrolimus trough levels (TLs). The aim of the study was to assess the impact of infection on tacrolimus TLs and to determine the factors involved in TL fluctuations. METHODS: This retrospective cohort study included patients transplanted with a kidney between 2009 and 2011 who were hospitalized for an acute infection...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149958/efficacy-of-prolonged-and-immediate-release-tacrolimus-in-kidney-transplantation-a-pooled-analysis-of-two-large-randomized-controlled-trials
#4
B K Krämer, L Albano, B Banas, B Charpentier, L Bäckman, H Tedesco-Silva, F Lehner, G A Mondragón-Ramírez, M Glyda, E Cassuto-Viguier, O Viklický, G Mourad, P Rigotti, S Schleibner, N Kamar
BACKGROUND: Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy). METHODS: Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, BCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction)...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149305/rituximab-for-non-responsive-idiopathic-membranous-nephropathy-in-a-chinese-cohort
#5
Xin Wang, Zhao Cui, Yi-Miao Zhang, Zhen Qu, Fang Wang, Li-Qiang Meng, Xu-Yang Cheng, Gang Liu, Fu-de Zhou, Ming-Hui Zhao
Background: Rituximab had been shown to be effective in inducing remission of nephrotic syndrome in patients with idiopathic membranous nephropathy (iMN). This study applied rituximab therapy for 36 non-responsive iMN patients to investigate its effects and safety. Methods: Thirty-six iMN patients who were non-responsive to prior immunosuppression were enrolled. Rituximab was used for B-cell depletion in patients, with a goal of <5 B cells/mm3 in the circulation...
November 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29148096/performance-of-the-dimension-tac-assay-and-comparison-of-multiple-platforms-for-the-measurement-of-tacrolimus
#6
Eun-Jung Cho, Dae-Hyun Ko, Woochang Lee, Sail Chun, Hae-Kyung Lee, Won-Ki Min
BACKGROUND: Therapeutic monitoring of tacrolimus is essential for reducing organ rejection and adverse effects. The measurement of tacrolimus in whole blood is taken by many automated platforms. We evaluated the analytical performance of the Dimension TAC assay, which is an upgraded reagent from the previous Dimension TACR assay. METHODS: The evaluations involved determination of precision, linearity, detection capability, and reagent lot-to-lot variability between three lot numbers...
November 17, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29146214/-treatments-of-steroid-dependent-nephrotic-syndrome-in-children
#7
A Couderc, E Bérard, V Guigonis, I Vrillon, J Hogan, V Audard, V Baudouin, C Dossier, O Boyer
Primary nephrotic syndrome (NS) is the most common glomerular disease in children. It is characterized by massive proteinuria and hypoalbuminemia. It typically has a sudden onset and more than 70% of patients will experience at least one relapse. An immunological origin has long been postulated, although the precise molecular mechanisms underlying the disease remain debated. Steroids are the first-line therapy with cumulative dose and duration of initial treatment varying among countries. Steroid-sparing agents may be indicated in case of steroid-dependency or frequent relapses...
November 13, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29142979/two-year-follow-up-study-of-membranous-nephropathy-treated-with-tacrolimus-and-corticosteroids-versus-cyclical-corticosteroids-and-cyclophosphamide
#8
Raja Ramachandran, Ashok Kumar Yadav, Vinod Kumar, Venkata Siva Tez Pinnamaneni, Ritambhra Nada, Ratan Ghosh, Vivek Kumar, Manish Rathi, Harbir Singh Kohli, Krishan Lal Gupta, Vinay Sakhuja, Vivekanand Jha
Introduction: Both cCTX/GCs and CNIs are recommended as first-line agents in the management of PMN. The present study is an extended report of patients randomized to receive TAC/GCs or cCTX/GCs at 2 years post randomization. Methods: Seventy patients enrolled in the clinical trial Tacrolimus Combined With Corticosteroids Versus Modified Ponticelli Regimen in Treatment of Idiopathic Membranous Nephropathy: Randomized Control Trial were followed quarterly between 12 and 24 months...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29136956/antagonistic-effect-of-oxytocin-and-tacrolimus-combination-on-adipose-tissue-derived-mesenchymal-stem-cells-antagonistic-effect-of-oxytocin-and-tacrolimus-antagonistic-effect-of-oxytocin-and-tacrolimus
#9
Gozde Sir, Bakiye Goker Bagca, Gurkan Yigitturk, Turker Cavusoglu, Cigir Biray Avci, Cumhur Gunduz, Yigit Uyanikgil
Tacrolimus (FK506) is a chemotherapeutic agent, which uses calcineurin pathway via inhibiting the stimulation of T cells to prevent the formation of immune response in the recipient individual in organ transplants. FK506 is mainly metabolized in the liver by cytochrome P450 enzyme system and is known that it has high toxic effects on different cells. Mesenchymal stem cells (MSCs) have recently gained importance since their potential to be used in cellular therapy and tissue regeneration. In some clinical cases, MSCs are transferred into the patient after the organ transplantations in order to support the treatment...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135993/bioequivalence-between-innovator-and-generic-tacrolimus-in-liver-and-kidney-transplant-recipients-a-randomized-crossover-clinical-trial
#10
Rita R Alloway, Alexander A Vinks, Tsuyoshi Fukuda, Tomoyuki Mizuno, Eileen C King, Yuanshu Zou, Wenlei Jiang, E Steve Woodle, Simon Tremblay, Jelena Klawitter, Jost Klawitter, Uwe Christians
BACKGROUND: Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand") product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29135980/bioequivalence-of-twice-daily-oral-tacrolimus-in-transplant-recipients-more-evidence-for-consensus
#11
Simon Ball
In this Perspective on the clinical trial by Rita Alloway and colleagues, Simon Ball explains the benefits to healthcare systems and individual patients of the bioequivalence established between generic and brand-name formulations of an immunosuppressive drug in transplant recipients.
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29133776/tacrolimus-levels-are-not-associated-with-risk-of-malignancy-in-lung-transplant-recipients
#12
Benjamin Daniel Fox, Fadi Ashquar, Yael Raviv, Dror Rozengarten, Osnat Straichman, Shimon Izhakian, Mordechai Reuven Kramer
BACKGROUND Lung transplant (LTx) recipients suffer from high rates of malignancy. Exposure to immunosuppressive medication such as tacrolimus has been proposed as a risk factor for tumorigenesis. We hypothesized that chronically high levels of tacrolimus would be associated with risk of malignancy. MATERIAL AND METHODS The study was performed in a transplant center in Israel, with a nested case-control design. Cases were LTx recipients who were diagnosed with any solid or hematological malignancy except non-melanoma skin cancer...
November 14, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29132395/impaired-mitochondrial-calcium-uptake-caused-by-tacrolimus-underlies-beta-cell-failure
#13
Angela Lombardi, Bruno Trimarco, Guido Iaccarino, Gaetano Santulli
BACKGROUND: One of the most common side effects of the immunosuppressive drug tacrolimus (FK506) is the increased risk of new-onset diabetes mellitus. However, the molecular mechanisms underlying this association have not been fully clarified. METHODS: We studied the effects of the therapeutic dose of tacrolimus on mitochondrial fitness in beta-cells. RESULTS: We demonstrate that tacrolimus impairs glucose-stimulated insulin secretion (GSIS) in beta-cells through a previously unidentified mechanism...
November 13, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29130957/clinical-disease-patterns-in-a-regional-swiss-cohort-of-34-pyoderma-gangrenosum-patients
#14
Antonios G A Kolios, Alissa Gübeli, Barbara Meier, Julia-Tatjana Maul, Thomas Kündig, Jakob Nilsson, Jürg Hafner, Emmanuella Guenova, Katrin Kerl, Mark Anliker, Werner Kempf, Alexander A Navarini, Lars E French, Antonio Cozzio
BACKGROUND/AIM: Pyoderma gangrenosum (PG) is a rare, neutrophilic dermatosis often associated with an underlying disease, and clinical data or larger studies are rare. METHODS: In this retrospective study, disease characteristics, clinical manifestations, and treatment response were evaluated in a Swiss cohort of PG patients. RESULTS: In participating centers, 34 cases (21 females) of PG were analyzed based on clinical and histological presentation between 2002 and 2012...
November 7, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/29128555/combined-haploidentical-and-umbilical-cord-blood-allogeneic-stem-cell-transplantation-for-high-risk-lymphoma-and-cll
#15
Jingmei Hsu, Andrew Artz, Sebastian A Mayer, Danielle Guarner, Michael R Bishop, Ronit Reich-Slotky, Sonali M Smith, June Greenberg, Justin Kline, Rosanna Ferrante, Adrienne A Phillips, Usama Gergis, Hongtao Liu, Wendy Stock, Melissa Cushing, Tsiporah B Shore, Koen van Besien
Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and CLL patients who underwent haplo-cord allogeneic stem cell transplantation...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29127611/tacrolimus-as-an-adjunct-to-autologous-minced-muscle-grafts-for-the-repair-of-a-volumetric-muscle-loss-injury
#16
Benjamin T Corona, Jessica C Rivera, Joseph C Wenke, Sarah M Greising
BACKGROUND: Volumetric muscle loss (VML) following extremity orthopaedic trauma or surgery results in chronic functional deficits and disability. A current translational approach to address the devastating functional limitations due to VML injury is the use of an autologous minced muscle graft (~1 mm(3) pieces of muscle tissue) replacement into the injured defect area, although limitations related to donor site morbidity are still unaddressed. This study was designed to explore adjunct pharmacological immunomodulation to enhance graft efficacy and promote muscle function following VML injury, and thereby reduce the amount of donor tissue required...
November 10, 2017: Journal of Experimental Orthopaedics
https://www.readbyqxmd.com/read/29127275/allogeneic-stem-cell-transplantation-in-fully-mhc-matched-mauritian-cynomolgus-macaques-recapitulates-diverse-human-clinical-outcomes
#17
Benjamin J Burwitz, Helen L Wu, Shaheed Abdulhaqq, Christine Shriver-Munsch, Tonya Swanson, Alfred W Legasse, Katherine B Hammond, Stephanie L Junell, Jason S Reed, Benjamin N Bimber, Justin M Greene, Gabriela M Webb, Mina Northrup, Wolfram Laub, Paul Kievit, Rhonda MacAllister, Michael K Axthelm, Rebecca Ducore, Anne Lewis, Lois M A Colgin, Theodore Hobbs, Lauren D Martin, Betsy Ferguson, Charles R Thomas, Angela Panoskaltsis-Mortari, Gabrielle Meyers, Jeffrey J Stanton, Richard T Maziarz, Jonah B Sacha
Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.-tumor immunity are hampered by the lack of a physiologically relevant, preclinical model of allogeneic HSCT. Here we show a spectrum of diverse clinical HSCT outcomes including primary and secondary graft failure, lethal GvHD, and stable, disease-free full donor engraftment using reduced intensity conditioning and mobilized peripheral blood HSCT in unrelated, fully MHC-matched Mauritian-origin cynomolgus macaques...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29123971/concepts-of-genomics-in-kidney-transplantation
#18
William S Oetting, Casey Dorr, Rory P Remmel, Arthur J Matas, Ajay K Israni, Pamala A Jacobson
Purpose of review: Identification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes. Recent findings: Many studies have yet to exhibit robust and reproducible results, however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant...
June 2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29123208/differential-t-cell-signaling-pathway-activation-by-tacrolimus-and-belatacept-after-kidney-transplantation-post-hoc-analysis-of-a-randomised-controlled-trial
#19
Nynke M Kannegieter, Dennis A Hesselink, Marjolein Dieterich, Gretchen N de Graav, Rens Kraaijeveld, Carla C Baan
Pharmacokinetic immunosuppressive drug monitoring poorly correlates with clinical outcomes after solid organ transplantation. A promising method for pharmacodynamic monitoring of tacrolimus (TAC) in T cell subsets of transplant recipients might be the measurement of (phosphorylated) p38MAPK, ERK1/2 and Akt (activated downstream of the T cell receptor) by phospho-specific flow cytometry. Here, blood samples from n = 40 kidney transplant recipients (treated with either TAC-based or belatacept (BELA)-based immunosuppressive drug therapy) were monitored before and throughout the first year after transplantation...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29118700/looking-beyond-the-cyclosporine-swish-and-spit-technique-in-a-recalcitrant-case-of-erosive-lichen-planus-involving-the-tongue
#20
Aastha Gupta, Kabir Sardana, Ram Kishan Gautam
Oral lichen planus is a relatively common autoimmune disease affecting the middle-aged population. Although no treatment is necessary for a benign asymptomatic case, in case of erosive lichen planus, topical corticosteroids form the mainstay of treatment. In case of failure, apart from tacrolimus, cyclosporine, using the "swish and spit" technique, is a valid therapeutic intervention. In our case, though, this therapeutic option had to be replaced by the systemic use of cyclosporine with gratifying results.
September 2017: Case Reports in Dermatology
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