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everolimus and transplantation

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https://www.readbyqxmd.com/read/28548030/everolimus-inhibited-multiple-isoforms-of-udp-glucuronosyltransferases-ugts
#1
Zuo Du, Guang Wang, Yun-Feng Cao, Cui-Min Hu, Kun Yang, Yong-Zhe Liu, Chun-Ze Zhang, Wei-Hua Zhang, Zhi-Tu Zhu, Hong-Zhi Sun, Xiao-Yu Sun, Mo Hong, Zhong-Ze Fang
1. Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and has been clinically utilized to prevent the rejection of organ transplants. This study aims to determine the inhibition of everolimus on the activity of phase II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). 2. The results showed that 100 uM of everolimus exerted more than 80% inhibition towards UGT1A1, -1A3, and -2B7. UGT1A3 and UGT2B7 were selected to elucidate the inhibition mechanism, and in silico docking showed that hydrogen bonds and hydrophobic interactions mainly contributed to the strong binding of everolimus towards the activity cavity of UGT1A3 and UGT2B7...
May 26, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28546531/supplementary-administration-of-everolimus-reduces-cardiac-systolic-function-in-kidney-transplant-recipients
#2
Kazuma Tsujimura, Morihito Ota, Kiyoshi Chinen, Kiyomitsu Nagayama, Masato Oroku, Morikuni Nishihira, Yoshiki Shiohira, Masami Abe, Kunitoshi Iseki, Hideki Ishida, Kazunari Tanabe
BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation...
May 26, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28542523/impact-of-maintenance-immunosuppressive-therapy-on-the-fecal-microbiome-of-renal-transplant-recipients-comparison-between-an-everolimus-and-a-standard-tacrolimus-based-regimen
#3
Gianluigi Zaza, Alessandra Dalla Gassa, Giovanna Felis, Simona Granata, Sandra Torriani, Antonio Lupo
BACKGROUND: The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. METHODS: We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols...
2017: PloS One
https://www.readbyqxmd.com/read/28511172/donor-specific-anti-human-leukocyte-antigens-antibodies-acute-rejection-renal-function-and-histology-in-kidney-transplant-recipients-receiving-tacrolimus-and-everolimus
#4
Alexandra Ferreira, Claudia Felipe, Marina Cristelli, Laila Viana, Geovana Basso, Suelen Stopa, Juliana Mansur, Mayara Ivani, Adrieli Bessa, Priscila Ruppel, Wilson Aguiar, Erika Campos, Maria Gerbase-DeLima, Henrique Proença, Helio Tedesco-Silva, José Medina-Pestana
BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101)...
May 17, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28508247/in-human-cell-cultures-everolimus-is-inferior-to-tacrolimus-in-inhibiting-cellular-alloimmunity-but-equally-effective-as-regards-humoral-alloimmunity
#5
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Nikolaos Antoniadis, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft failure early in the course of kidney transplantation, whereas chronic antibody-mediated rejection is a major contributor to graft loss in the late post-transplant phase. Based mainly on the results of short-term studies, the calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin (mTOR) inhibitors. However, the toxicity profile of the two drug categories differs, making the interchange between them appealing...
May 15, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28507917/systemic-meta-analysis-assessing-the-short-term-applicability-of-early-conversion-to-mammalian-target-of-rapamycin-inhibitors-in-kidney-transplant
#6
Jayant Kumar, Isabella Reccia, Tomokazu Kusano, Bridson M Julie, Ajay Sharma, Ahmed Halawa
AIM: To consolidate the present evidence of effectiveness in renal functioning and graft survival following early introduction of mammalian target of rapamycin (mTOR) inhibitors with or without calcineurin inhibitors (CNIs) in renal transplant recipients. METHODS: We analysed the current literature following PROSPERO approval describing the role of immunosuppressive agent, mTOR inhibitors as an alternative to CNI within six months of renal transplant by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus using MeSH terms...
April 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28479418/development-of-an-assay-for-cellular-efflux-of-pharmaceutically-active-agents-and-its-relevance-to-understanding-drug-interactions
#7
Benigno C Valdez, Moustapha Hassan, Borje S Andersson
Drug interactions may dictate the failure or success of a treatment. Patients undergoing hematopoietic stem cell transplantation (HSCT) are exposed to various types of drugs and it is of utmost importance to understand how these drugs interact. The pharmacokinetics of busulfan, melphalan and cyclophosphamide, commonly used drugs in HSCT, are known to be affected by a variety of drugs with differing molecular structures. We hypothesized that these structurally-unrelated drugs affect the transport of DNA alkylating agents...
May 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28463861/everolimus-immunosuppression-for-renal-protection-reduction-of-allograft-vasculopathy-and-prevention-of-allograft-rejection-in-de-novo-heart-transplant-recipients-could-we-have-it-all
#8
Einar Gude, Lars Gullestad, Arne K Andreassen
PURPOSE OF REVIEW: De-novo introduction of everolimus (Eve) in heart transplant recipients opens for early reduction of calcineurin inhibitors (CNI) and potential of preserving renal function, attenuate progression of coronary allograft vasculopathy (CAV) and maintain rejection efficacy. RECENT FINDINGS: The first trials demonstrated adequate rejection prophylaxis and favorable outcomes on CAV, but observed enhanced nephrotoxicity because of insufficient CNI reduction...
June 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28457410/immunomodulation-acute-renal-failure-and-complications-of-basiliximab-use-after-liver-transplantation-analysis-of-114-patients-and-literature-review
#9
E C de Ataide, S R Perales, J B Bortoto, M A O Peres, F C Filho, R S B Stucchi, E Udo, I F S F Boin
Basiliximab is considered to be effective in preventing cellular rejection (CR) in solid organ transplantation and is commonly used for renal transplants. The aim of this study was describe the population of patients undergoing orthotopic liver transplantation (LT) receiving basiliximab in the period 2012-2016 in the liver transplant service at the State University of Campinas, São Paulo, Brazil. We analyzed 114 patients who underwent LT and received basiliximab; 83 (72.8%) were male and 31 (27.2%) female, with an overall mean age of 54...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28452165/cutaneous-toxicities-from-transplant-related-medications
#10
M Ilyas, O R Colegio, B Kaplan, A Sharma
Despite the abundance of information on cutaneous malignancies associated with solid organ transplantation in the transplant literature, there is limited information regarding non-malignant skin changes after transplantation. There are numerous skin toxicities secondary to immunosuppressive and other transplant-related medications that can vary in presentation, severity, and prognosis. In order to limit associated morbidity and mortality, SOTR care providers should effectively identify and manage cutaneous manifestations secondary to drug toxicity...
April 27, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28425200/high-dose-calcineurin-inhibitor-free-everolimus-as-a-maintenance-regimen-for-heart-transplantation-may-be-a-risk-factor-for%C3%A2-pneumocystis-pneumonia
#11
Yu-Ning Hu, Nan-Yao Lee, Jun-Neng Roan, Chi-Hsin Hsu, Chwan-Yao Luo
BACKGROUND: Everolimus reduces the incidence of cardiac-allograft vasculopathy (CAV) and is less renally toxic than are calcineurin inhibitors (CNIs). We evaluated the safety of CNI-free everolimus for post-heart transplant (HTx) patients. METHODS: We retrospectively reviewed the records of 36 consecutive patients who had undergone an HTx between January 2006 and December 2013 in National Cheng Kung University Hospital. All patients initially had been treated with the standard tacrolimus regimen...
April 20, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28416360/primary-hepatic-angiosarcoma-and-liver-transplantation-radiological-surgical-histological-findings-and-clinical-outcome
#12
M Tran Minh, A Mazzola, F Perdigao, F Charlotte, G Rousseau, F Conti
Angiosarcoma is a rare type of soft tissue sarcoma that accounts for less than 1% of all sarcomas and only 2% of all primary hepatic tumours. Thorotrast, arsenic, and vinyl chloride monomer are frequently listed as occupational exposure risks. The estimated latency is long (10-40 years) in occupational cases and very long (60 years or more) in non-occupational cases. The symptoms and CT-scan appearance of hepatic angiosarcoma (HAS) are non-specific. We present a case of a 65-year-old Caucasian male with history of cryptogenic cirrhosis, low alpha-foetoprotein levels and a single, 4-cm nodule of potential atypical hepatocellular carcinoma (no washout at MRI and CT-scan) in segment VIII...
April 14, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28415888/bioengineered-gold-nanoparticles-targeted-to-mesenchymal-cells-from-patients-with-bronchiolitis-obliterans-syndrome-does-not-rise-the-inflammatory-response-and-can-be-safely-inhaled-by-rodents
#13
Emanuela Cova, Simona Inghilleri, Laura Pandolfi, Monica Morosini, Sara Magni, Miriam Colombo, Davide Piloni, Chiara Finetti, Gabriele Ceccarelli, Laura Benedetti, Maria Gabriella Cusella, Manuela Agozzino, Fabio Corsi, Raffaele Allevi, Simona Mrakic-Sposta, Sarah Moretti, Simona De Gregori, Davide Prosperi, Federica Meloni
The use of gold nanoparticles as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favours epithelial mesenchymal transition and activation of local mesenchymal cells leading to airway fibro-obliteration...
April 18, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28405603/mtor-inhibition-by-everolimus-does-not-impair-closure-of-punch-biopsy-wounds-in-renal-transplant-patients
#14
Shelley B Dutt, Josephine Gonzales, Megan Boyett, Anne Costanzo, Peggy P Han, Steven Steinberg, Dianne B McKay, Julie M Jameson
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are approved to prevent allograft rejection and control malignancy. Unfortunately, they are associated with adverse effects, such as wound healing complications that detract from more extensive use. There is a lack of prospective wound healing studies to monitor patients treated with mTOR inhibitors, such as everolimus or sirolimus, especially in nondiabetics. METHODS: Patients receiving everolimus with standard immunosuppressant therapy or standard immunosuppressant therapy without everolimus were administered 3-mm skin biopsy punch wounds in the left scapular region...
April 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28345271/immunosuppression-with-mtor-inhibitors-prevents-the-development-of-donor-specific-antibodies-after-liver-transplant
#15
Katharina Willuweit, Andreas Heinold, Jassin Rashidi-Alavijeh, Falko M Heinemann, Peter A Horn, Andreas Paul, Guido Gerken, Kerstin Herzer
BACKGROUND: Donor-specific antibodies (DSAs) are an important cause of complications after solid organ transplant. Risk factors and, thus, strategies for preventing DSA development are not well defined. METHODS: The DSA status of 400 patients who underwent liver transplant (LT) at the outpatient clinic of the University Hospital Essen was determined. Human leukocyte antigen (HLA) antibodies were detected by single-antigen bead technology. The strength of DSAs was reported as mean fluorescence intensity...
March 26, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28340831/pregnancy-and-delivery-in-the-sequel-of-kidney-transplantation-single-center-study-of-8-years-experience
#16
Y Yuksel, S Tekin, D Yuksel, I Duman, M Sarier, L Yucetin, E Turan, H Celep, T Ugurlu, M M Inal, Y H Asuman, A Demirbas
BACKGROUND: Depending on hyphothalamic, hyphophyseal, and gonadal axis dysfunction, anovulatory irregular cycles occur and the probability of pregnancy decreases in the patients with chronic kidney disease (CKD). Maternal mortality and morbidity rates are increased in CKD patients; the risk of premature delivery is 70% and the risk of preeclampsia is 40% more than normal among those with a creatine level of >2.5 mg/dL. METHODS: If a pregnancy is expected in the sequel of kidney transplantation (KT), a multidisciplinary team approach should be adopted and both the gynecologist and the nephrologist should follow the patient simultaneously...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28340820/role-of-everolimus-on-cardiac-functions-in-kidney-transplant-recipients
#17
U Cakir, G Alis, T Erturk, A H Karayagiz, U Karabulut, I Berber
BACKGROUND: Kidney transplantation is known to increase the survival of dialysis patients by ameloriating cardiac status, including both systolic and diastolic functions. We aimed to evaluate the role of immunosuppressive drug regimens on cardiac functions of kidney transplant recipients (KTRs). METHODS: We prospectively evaluated 120 KTRs immediately before and 1 year after the kidney transplantation, using tissue Doppler echocardiography. A triple immunosuppressive therapy including tacrolimus, mycophenoloic acid (MPA), and prednisolone was started for all patients...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28340815/expression-profile-of-microrna-biogenesis-components-in-renal-transplant-patients
#18
E Celen, M G Ertosun, H Kocak, A Dinckan, B Yoldas
BACKGROUND: MicroRNAs (miRNAs) and the miRNA biogenesis components are potential biomarkers of some prevalent diseases, such as cancer and diabetes. In light of this information, we aimed to investigate the expression profiles of miRNA biogenesis components in renal transplant patients before and after transplantation and how these profiles are related to immunosuppressive treatment and clinical outcomes of these patients. METHODS: In this study, gene and protein expression profiles of Dicer, Drosha, Pasha (DGCR8), Exportin5 (XPO5), and Argonaute2 (AGO2) in peripheral blood mononuclear cells (PBMCs) of renal transplant patients were evaluated by means of real-time quantitative polymerase chain reaction and Western blot methods before and 3 months after transplantation...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28333860/cardiovascular-parameters-to-2-years-after-kidney-transplantation-following-early-switch-to-everolimus-without-calcineurin-inhibitor-therapy-an-analysis-of-the-randomized-elevate-study
#19
Hallvard Holdaas, Johan W de Fijter, Josep M Cruzado, Pablo Massari, Björn Nashan, John Kanellis, Oliver Witzke, Alex Gutierrez-Dalmau, Aydin Turkmen, Zailong Wang, Patricia Lopez, Peter Bernhardt, Jossy Kochuparampil, Markus van der Giet, Klaus Murbraech
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may confer cardioprotective advantages but clinical data are limited. METHODS: In the open-label ELEVATE trial, kidney transplant patients were randomized at 10-14 weeks posttransplant to convert from calcineurin inhibitor (CNI) to everolimus or remain on standard CNI therapy. Prespecified endpoints included left ventricular mass index (LVMi) and, in a subpopulation of patients, arterial stiffness as measured by pulse wave velocity (PWV)...
March 22, 2017: Transplantation
https://www.readbyqxmd.com/read/28332959/de-novo-donor-specific-antibody-formation-in-tacrolimus-based-mycophenolate-versus-mammalian-target-of-rapamycin-immunosuppressive-regimens
#20
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
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