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mycophenolate levels

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https://www.readbyqxmd.com/read/28332959/de-novo-donor-specific-antibody-formation-in-tacrolimus-based-mycophenolate-versus-mammalian-target-of-rapamycin-immunosuppressive-regimens
#1
Zain Mithani, Jane Gralla, Oluwafisayo Adebiyi, Patrick Klem, James E Cooper, Alexander C Wiseman
OBJECTIVES: De novo donor-specific antibody formation posttransplant is associated with decreased graft survival. It is not known whether mammalian target of rapamycin inhibitors may be advantageous or detrimental compared with mycophenolate in the prevention of de novo donor-specific antibody formation. MATERIALS AND METHODS: We compared 66 kidney and kidney-pancreas transplant recipients who received tacrolimus, mammalian target of rapamycin inhibitor, and prednisone (group 1; 36 of whom received everolimus and 30 of whom received sirolimus) versus 132 patients who received tacrolimus, mycophenolate, and prednisone (group 2) matched for age, sex, race, and type/timing of transplant from 2007 to 2012...
March 22, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28327659/the-immunosuppressant-mycophenolic-acid-alters-nucleotide-and-lipid-metabolism-in-an-intestinal-cell-model
#2
Svenja Heischmann, Monika Dzieciatkowska, Kirk Hansen, Dieter Leibfritz, Uwe Christians
The study objective was to elucidate the molecular mechanisms underlying the negative effects of mycophenolic acid (MPA) on human intestinal cells. Effects of MPA exposure and guanosine supplementation on nucleotide concentrations in LS180 cells were assessed using liquid chromatography-mass spectrometry. Proteomics analysis was carried out using stable isotope labeling by amino acids in cell culture combined with gel-based liquid chromatography-mass spectrometry and lipidome analysis using (1)H nuclear magnetic resonance spectroscopy...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317040/intra-individual-variability-of-mycophenolic-acid-concentration-according-to-renal-function-in-liver-transplant-recipients-receiving-mycophenolate-monotherapy
#3
Shin Hwang, Gi-Won Song, Dong-Hwan Jung, Gil-Chun Park, Chul-Soo Ahn, Deok-Bog Moon, Tae-Yong Ha, Ki-Hun Kim, Sung-Gyu Lee
BACKGROUNDS/AIMS: Mycophenolate mofetil (MMF) has wide inter- and intra-individual variability of mycophenolic acid (MPA) after liver transplantation (LT). On this study, we aimed to analyse the intra-individual variability of MPA concentration in stable adult LT recipients receiving MMF monotherapy and develop a method to determine the target level in the situation of wide intra-individual variability. METHODS: This retrospective cross-sectional study included 30 LT recipients...
February 2017: Ann Hepatobiliary Pancreat Surg
https://www.readbyqxmd.com/read/28314079/low-serum-testosterone-is-associated-with-graft-function-early-after-heart-transplantation
#4
Gregor Poglajen, Mojca Jensterle, Nika Kravos, Andrej Janež, Bojan Vrtovec
BACKGROUND: We sought to investigate a correlation between serum testosterone levels and graft function early after heart transplantation. METHODS: In a cross-sectional study we measured serum testosterone levels 4 weeks after heart transplantation in 49 consecutive male recipients. Echocardiography was done to evaluate graft function. Low serum testosterone was defined as <11 nmol/L. RESULTS: Low serum testosterone was present in 21 (43%) recipients (Group A), and 28 (57%) had normal testosterone levels (Group B)...
March 17, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28300419/dried-blood-spot-validation-of-five-immunosuppressants-without-hematocrit-correction-on-two-lc-ms-ms-systems
#5
Remco A Koster, Herman Veenhof, Rixt Botma, Alle Tjipke Hoekstra, Stefan P Berger, Stephan Jl Bakker, Jan-Willem C Alffenaar, Daan J Touw
AIM: Hematocrit (Ht) effects remain a challenge in dried blood spot (DBS) sampling. The aim was to develop an immunosuppressant DBS assay on two LC-MS/MS systems covering a clinically relevant Ht range without Ht correction. RESULTS: The method was partially validated for tacrolimus, sirolimus, everolimus, cyclosporin A and fully validated for mycophenolic acid on an Agilent and Thermo LC-MS/MS system. Bias caused by Ht effects were within 15% for all immunosuppressants between Ht levels of 0...
March 16, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28279567/optimizing-everolimus-exposure-when-combined-with-calcineurin-inhibitors-in-solid-organ-transplantation
#6
REVIEW
Teun van Gelder, Lutz Fischer, Fuad Shihab, Maria Shipkova
The mammalian target of rapamycin (mTOR) inhibitor everolimus is a narrow therapeutic index drug for which optimal exposure levels are essential. The consistent pharmacokinetic profile of everolimus allows trough concentration (C0) measurement to be an appropriate and reliable index for therapeutic drug monitoring (TDM). Exposure-response analyses of data from early fixed-dose trials demonstrated that rates of biopsy-proven acute rejection (BPAR) are significantly higher if everolimus C0 declines below 3 ng/mL, an observation confirmed in subsequent concentration-controlled trials...
February 27, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28276509/suppression-of-autophagy-by-mycophenolic-acid-contributes-to-inhibition-of-hcv-replication-in-human-hepatoma-cells
#7
Shoucai Fang, Jinming Su, Bingyu Liang, Xu Li, Yu Li, Junjun Jiang, Jiegang Huang, Bo Zhou, Chuanyi Ning, Jieliang Li, Wenzhe Ho, Yiping Li, Hui Chen, Hao Liang, Li Ye
Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28260426/borderline-changes-on-dysfunctional-renal-allograft-biopsies-clinical-relevance-in-a-living-related-renal-transplant-setting
#8
Muhammed Mubarak, Shaheera Shakeel, Khawar Abbas, Tahir Aziz, Mirza Naqi Zafar, Syed Anwer Naqvi, Syed Adibul Hasan Rizvi
OBJECTIVES: Our aim was to determine the clinical significance of borderline lymphocytic infiltrates on indicated renal allograft biopsies in a living related renal transplant setting. MATERIALS AND METHODS: The study was conducted at the histopathology department of Sindh Institute of Urology and Transplantation. A retrospective review of 421 renal transplant patients was conducted from October 2007 to September 2008 to identify patients in whom a histologic diagnosis of borderline changes was made on dysfunctional renal allograft biopsies...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28257599/immunosuppressive-drugs-affect-ifn%C3%AE-and-pd1-kinetics-in-patients-with-newly-diagnosed-autoimmune-hepatitis
#9
Charlotte R Grant, Beth S Holder, Rodrigo Liberal, Michael A Heneghan, Yun Ma, Giorgina Mieli-Vergani, Diego Vergani, Maria Serena Longhi
Autoimmune hepatitis (AIH) is characterized by overwhelming effector immune responses associated with defective regulatory T cells (Tregs). Several lines of evidence indicate CD4 as the main effectors involved in the autoimmune liver damage. Herein we investigate the in vitro effects of prednisolone, 6-mercaptopurine, cyclosporine, tacrolimus, mycophenolic acid (MPA) and rapamycin, immunosuppressive drugs (ISDs) used in AIH treatment, on the expression of pro-inflammatory cytokines, co-inhibitory molecules and ability to proliferate of CD4(+) CD25(-) cells, isolated from the peripheral blood of treatment-naïve patients with AIH...
March 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28248797/metachronous-involvement-diagnostic-imprecision-of-serum-immunoglobulin-g4-levels-and-discordance-between-clinical-and-radiological-findings-in-immunoglobulin-g4-related-pachymeningitis-a-longitudinal-case-report
#10
Waqar Waheed, Philip Michael Skidd, Neil M Borden, Pamela C Gibson, Mohamed Ali Babi, Rup Tandan
Immunoglobulin G4-related disease is an increasingly recognized, idiopathic systemic disorder that might be associated with elevated serum IgG4 level and tissue infiltration by IgG4-positive plasma cells. We describe the clinical features and biopsy findings in a patient who presented with features suggestive of pachymeningitis and multiple cranial neuropathies. Meningeal biopsy and other laboratory studies established the diagnosis of IgG4-related hypertrophic pachymeningitis. Despite treatment with corticosteroids and mycophenolate mofetil, the patient exhibited a fluctuating progressive course, which stabilized with rituximab, although the radiological findings persisted over 2½ years of follow-up...
February 28, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28174010/a-case-of-t-cell-lymphoproliferative-disorder-associated-with-hypereosinophilia-with-excellent-response-to-mycophenolate-mofetil
#11
Amr Hanbali, Marwan Shaheen, Feras Alfraih, Wafa Al-Otaibi, Riad El Fakih, Tarek Owaidah, Syed Ahmed
Hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by a persistent elevation of blood eosinophil count ⩾1.5×10(9)/L and clinical manifestations attributable to eosinophilia or tissue hypereosinophilia. Lymphocytic variant of HES (HES-L) is a known subtype according to World Health Organization classification. It is well documented in the literature that patients with HES-L are predisposed to develop T-cell lymphoma. We report a case of T-cell lymphoproliferation associated with hypereosinophilia, which has been successfully treated with mycophenolate mofetil, with resolution of skin lesions and normalization of eosinophil count and immunoglobulin E level...
February 1, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28148558/risk-factors-for-renal-survival-in-chinese-patients-with-myeloperoxidase-anca-associated-gn
#12
Yinghua Chen, Hao Bao, Zhengzhao Liu, Xia Liu, Erzhi Gao, Caihong Zeng, Haitao Zhang, Zhihong Liu, Weixin Hu
BACKGROUND AND OBJECTIVES: Our study explored the association of histopathologic classification of ANCA-associated GN with renal survival in Chinese patients with myeloperoxidase-ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two hundred fifteen patients with biopsy-proven myeloperoxidase-ANCA-associated GN were included from January of 1996 to December of 2014. The biopsies included focal (n=27), mixed (n=82), crescentic (n=47), and sclerotic (n=59) classes...
March 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28145625/pediatric-renal-transplant-practices-in-india
#13
Sidharth Kumar Sethi, Rajiv Sinha, Smriti Rohatgi, Vijay Kher, Arpana Iyengar, Arvind Bagga
Limited access to tertiary-level health care, limited trained pediatric nephrologists and transplant physicians, lack of facilities for dialysis, lack of an effective deceased donor program, non-affordability, and non-adherence to immunosuppressant drugs poses a major challenge to universal availability of pediatric transplantation in developing countries. We present the results of a survey which, to the best of our knowledge, is the first such published attempt at understanding the current state of pediatric renal transplantation in India...
February 1, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28133906/efficacy-and-safety-of-everolimus-and-mycophenolic-acid-with-early-tacrolimus-withdrawal-after-liver-transplantation-a-multicenter-randomized-trial
#14
Faouzi Saliba, Christophe Duvoux, Jean Gugenheim, Nassim Kamar, Sébastien Dharancy, Ephrem Salamé, Martine Neau-Cransac, François Durand, Pauline Houssel-Debry, Claire Vanlemmens, Georges Pageaux, Jean Hardwigsen, Daniel Eyraud, Yvon Calmus, Fabienne Di Giambattista, Jérôme Dumortier, Filomena Conti
SIMCER was a six-month, multicenter, open-label trial. Selected de novo liver transplant recipients were randomized (week 4) to everolimus with low-exposure tacrolimus discontinued by month 4 (n=93), or tacrolimus-based therapy (n=95), both with basiliximab induction and enteric-coated mycophenolate sodium ± steroids. The primary endpoint, change in estimated GFR (eGFR, MDRD) from randomization to week 24 post-transplant, was superior with everolimus: mean eGFR change +1.1mL/min/1.73m(2)  for everolimus versus -13...
January 30, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28130037/assessing-interactions-of-binary-mixtures-of-penicillium-mycotoxins-pms-by-using-a-bovine-macrophage-cell-line-bomacs
#15
Se-Young Oh, Nina Cedergreen, Alexandros Yiannikouris, H V L N Swamy, Niel A Karrow
Penicillium mycotoxins (PMs) are toxic contaminants commonly found as mixtures in animal feed. Therefore, it is important to investigate potential joint toxicity of PM mixtures. In the present study, we assessed the joint effect of binary combinations of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA) and penicillic acid (PA) using independent action (IA) and concentration addition (CA) concepts. Previously published toxicity data (i.e. IC25; PM concentration that inhibited bovine macrophage (BoMacs) proliferation by 25%) were initially analyzed, and both concepts agreed that OTA+PA demonstrated synergism (p<0...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28089042/molecular-screening-of-xerophilic-aspergillus-strains-producing-mycophenolic-acid
#16
Bello Mouhamadou, Lucile Sage, Sophie Périgon, Virginie Séguin, Valérie Bouchart, Patrick Legendre, Mathilde Caillat, Hayet Yamouni, David Garon
Mycophenolic acid (MPA) is the fungal secondary metabolite displaying several biological properties. Up to now, screening of fungal strains producing MPA has mainly been the result of the search of this molecule in their culture medium by chemical methods. Here we developed a molecular approach by targeting the expression level of the MpaC gene encoding the polyketide synthase, one of the key enzymes involved in the MPA synthesis. Thirty xerophilic Aspergillus strains were identified using the RNA polymerase II subunit and the β-tubulin genes...
February 2017: Fungal Biology
https://www.readbyqxmd.com/read/28076831/dosing-time-dependent-oxidative-effects-of-an-immunosuppressive-drug-mycophenolate-mofetil-on-rat-kidneys
#17
Ichrak Dridi, Wafa Ben-Cherif, Hassiba Chahdoura, Zohra Haouas, Mossadok Ben-Attia, Karim Aouam, Alain Reinberg, Naceur A Boughattas
This study investigates whether the toxicity in kidneys as well as oxidative stress varied according to the dosing time of an immunosuppressive agent "mycophenolate mofetil (MMF)" in Wistar Rat. 300mg/kg of MMF was injected by intraperitonal at four different circadian stages (1, 7, 13 and 19h after light onset, HALO). Rats were sacrificed after 3days, and the kidneys were removed for determination of oxidative stress and histological analysis. Biochemical variable (creatinine, urea) was performed. Statistical analysis showed that MMF administration at 7 HALO produced a renal toxicity assessed by the significant increase in both blood creatinine and urea and antioxidant activity assessed by malondialdehyde and protein carbonyl levels indicating an induction of lipid peroxidation in oxidative damage...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28074365/determination-of-cytostatic-drugs-in-bes%C3%A3-s-river-ne-spain-and-comparison-with-predicted-environmental-concentrations
#18
Helena Franquet-Griell, Deborah Cornadó, Josep Caixach, Francesc Ventura, Silvia Lacorte
The number of cytostatic drugs used in cancer treatments is wide and increases every year; therefore, tools have been developed to predict their concentration in the environment to prioritize those for monitoring studies. In the present study, the predicted environmental concentrations (PECs) were calculated according to consumption data in Catalonia (NE Spain) for 2014. According to PECs and to the most widely reported compounds, 19 cytostatics were monitored in two sampling campaigns performed along the Besòs River...
January 10, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28051798/%C3%A2-conversion-to-mycophenolate-mofetil-monotherapy-in-liver-recipients-calcineurin-inhibitor-levels-are-key
#19
Blanca Norero, Carolina A Serrano, Alberto Sanchez-Fueyo, Ignacio Duarte, Javiera Torres, Mauricio Ocquetau, Francisco Barrera, Marco Arrese, Alejandro Soza, Carlos Benítez
 The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28038680/changes-in-plasma-cxcl4-levels-are-associated-with-improvements-in-lung-function-in-patients-receiving-immunosuppressive-therapy-for-systemic-sclerosis-related-interstitial-lung-disease
#20
Elizabeth R Volkmann, Donald P Tashkin, Michael D Roth, Philip J Clements, Dinesh Khanna, Daniel E Furst, Maureen Mayes, Julio Charles, Chi-Hong Tseng, Robert M Elashoff, Shervin Assassi
BACKGROUND: Increased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD in the context of a randomized controlled trial and to determine whether changes in CXCL4 levels in response to immunosuppression are associated with future progression of SSc-ILD...
December 30, 2016: Arthritis Research & Therapy
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