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Calcineurin inhibitor

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https://www.readbyqxmd.com/read/28915690/efficacy-and-safety-of-a-reduced-calcineurin-inhibitor-dose-combined-with-mycophenolate-mofetil-in-liver-transplant-patients-with-chronic-renal-dysfunction
#1
Pusen Wang, Weitao Que, Hao Li, Lvnan Yan, Zhiren Fu, Qifa Ye, Guihua Chen, Kefeng Dou, Shichun Lu, Zhanyu Yang, Zhijun Zhu, Zhihai Peng, Lin Zhong
Calcineurin inhibitors (CNIs) are frequently given at a reduced dose in combination with mycophenolate mofetil (MMF) to avoid nephrotoxicity, but the optimal reduction in CNI dose has not been established. In this prospective, open-label, multicenter study, liver transplant recipients with chronic renal dysfunction who were administered a CNI-based immunosuppressive regimen were included in the intent-to-treat (ITT) population. The primary endpoint was declination in renal function, which was defined as a ≥ 20% decrease in the glomerular filtration rate during the year following regimen adjustment...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912999/tacrolimus-aggravated-tube-feeding-syndrome-with-acute-renal-failure-in-a-pediatric-liver-transplant-recipient
#2
R Kula, M Melter, J Kunkel, C Dörfler, S Alikadic, B Knoppke, R Zant
Acute renal failure can be caused by calcineurin inhibitors (CNIs), due to arteriolopathy and altered tubular function. Within this context, we present the case of a 14-month-old liver transplant recipient who suffered an acute polyuric renal failure during a short episode of hypercaloric feeding. In our case, CNI-induced distal RTA led to nephrocalcinosis and therefore to secondary nephrogenic diabetes insipidus. The diet with high renal solute load consequently resulted in an acute polyuric renal failure with severe hypernatremic dehydration...
2017: Case Reports in Transplantation
https://www.readbyqxmd.com/read/28906028/graft-outcomes-following-diagnosis-of-posttransplant-lymphoproliferative-disease-in-pediatric-kidney-recipients-a-retrospective-study
#3
Nele K Kanzelmeyer, Britta Maecker-Kolhoff, Henriette Zierhut, Christian Lerch, Murielle Verboom, Dieter Haffner, Lars Pape
Data related to graft outcomes following posttransplant lymphoproliferative disease (PTLD) in pediatric kidney transplantation are scarce. Data were analyzed retrospectively from 12 children (8 boys) for three years after diagnosis of PTLD, with a loss of follow-up after 2 years in 2/12. In all cases, intensity of immunosuppressive therapy was reduced, with switch from calcineurin inhibitor to a mammalian target of rapamcyin (mTOR) inhibitor in 6 cases. Nine children were treated with 6 doses of rituximab according to the PED-PTLD-2005 protocol, with additional treatment in one child as per protocol...
September 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28904428/collapsing-glomerulopathy-a-troublemaker-for-the-renal-allograft-lessons-learnt
#4
K V Kanodia, A V Vanikar, L K Nigam, R D Patel, K S Suthar, H V Patel, H L Trivedi
Collapsing glomerulopathy (CG) is a well-recognized distinct morphological pattern of proliferative parenchymal injury leading to rapid graft failure. We conducted a single-center retrospective study to evaluate the prevalence, clinicopathological features, and prognosis of CG in renal transplant recepient. We analyzed 2518 renal allograft biopsies performed from 2007 to 2015 and correlated their clinicopathological features. The prevalence of CG was 0.83% (21 out of 2518) of allograft biopsies with a higher prevalence of 1...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28899790/alisporivir-rescues-defective-mitochondrial-respiration-in-duchenne-muscular-dystrophy
#5
Marco Schiavone, Alessandra Zulian, Sara Menazza, Valeria Petronilli, Francesco Argenton, Luciano Merlini, Patrizia Sabatelli, Paolo Bernardi
Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtained from muscle biopsies of DMD patients display a decrease of the respiratory reserve, a consequence of inappropriate opening of the permeability transition pore (PTP). Treatment with the cyclophilin inhibitor alisporivir - a cyclosporin A derivative that desensitizes the PTP but does not inhibit calcineurin - largely restored the maximal respiratory capacity without affecting basal oxygen consumption in cells from patients, thus reinstating a normal respiratory reserve...
September 9, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28899698/betulinic-acid-derivative-ba5-a-dual-nf-kb-calcineurin-inhibitor-alleviates-experimental-shock-and-delayed-hypersensitivity
#6
Cássio Santana Meira, Renan Fernandes do Espírito Santo, Tatiana Barbosa Dos Santos, Iasmim Diniz Orge, Dahara Keyse Carvalho Silva, Elisalva Teixeira Guimarães, Luciana Souza de Aragão França, José Maria Barbosa-Filho, Diogo Rodrigo Magalhães Moreira, Milena Botelho Pereira Soares
Betulinic acid (BA) is a naturally occurring triterpenoid with several biological properties already described, including immunomodulatory activity. Here we investigated the immunomodulatory activity of eight semi-synthetic amide derivatives of betulinic acid. Screening of derivatives BA1-BA8 led to the identification of compounds with superior immunomodulatory activity than BA on activated macrophages and lymphocytes. BA5, the most potent derivative, inhibited nitric oxide and TNFα production in a concentration-dependent manner, and decreased NF-κB activation in Raw 264...
September 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28895956/atopic-dermatitis-skin-care-and-topical-therapies
#7
David M Fleischer, Jeremy Udkoff, Jenna Borok, Adam Friedman, Noreen Nicol, Jeffrey Bienstock, Peter Lio, Megha M Tollefson, Lawrence F Eichenfield
Atopic dermatitis (AD) pathogenesis is strongly influenced by Type 2 innate lymphoid cell and T-helper cell type 2 lymphocyte-driven inflammation and skin barrier dysfunction. AD therapies attempt to correct this pathology, and guidelines suggest suggest basics of AD therapy, which include repair of the skin barrier through bathing practices and moisturizers, infection control, and further lifestyle modifications to avoid and reduce AD triggers.While some patients' AD may be controlled using these measures, inflammatory eczema including acute flares and maintenance therapy in more severe patients are treated with topical pharmacologic agents such as topical corticosteroids, topical calcineurin inhibitors, and, more recently, topical PDE-4 inhibitors...
September 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28890387/peptides-derived-from-transcription-factor-eb-bind-to-calcineurin-at-a-similar-region-as-the-nfat-type-motif
#8
Ruiwen Song, Jing Li, Jin Zhang, Lu Wang, Li Tong, Ping Wang, Huan Yang, Qun Wei, Huaibin Cai, Jing Luo
Calcineurin (CN) is involved in many physiological processes and interacts with multiple substrates. Most of the substrates contain similar motifs recognized by CN. Recent studies revealed a new CN substrate, transcription factor EB (TFEB), which is involved in autophagy. We showed that a 15-mer QSYLENPTSYHLQQS peptide from TFEB (TFEB-YLENP) bound to CN. When the TFEB-YLENP peptide was changed to YLAVP, its affinity for CN increased and it had stronger CN inhibitory activity. Molecular dynamics simulations revealed that the TFEB-YLENP peptide has the same docking sites in CN as the 15-mer DQYLAVPQHPYQWAK motif of the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1-YLAVP)...
September 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28889715/-simultaneous-hepatorenal-transplantation-from-a-brain-dead-donor-for-graft-dysfunction-and-renal-insufficiency-in-a-liver-transplant-recipient-a-case-report
#9
Hideaki Takada, Takashi Kobayashi, Kohei Ogawa, Hitomi Miyata, Atsuro Sawada, Shusuke Akamatsu, Hiromitsu Negoro, Ryoichi Saito, Naoki Terada, Toshinari Yamasaki, Takahiro Inoue, Yuki Teramoto, Shinsuke Shibuya, Hironori Haga, Toshimi Kaido, Shinji Uemoto, Osamu Ogawa
We report a case of lethal hepatorenal insufficiency in a 52-year-old man who received successful simultaneous hepatorenal transplantation from a deceased donor. The patient had undergone live-donor liver transplantation for type-C hepatitis and liver cirrhosis 11 years before he developed graft liver dysfunction due to recurrent viral hepatitis and cirrhosis. At that instance, he also developed end-stage renal dysfunction due to calcineurin inhibitor nephropathy and hepatorenal syndrome. Although he needed three open hemostases and abundant blood transfusion, he was withdrawn from continuous hemodiafiltration on the 55th day and discharged from the hospital on the 272nd day postoperatively...
August 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28882776/immunosuppressant-medication-induced-lower-extremity-pain-after-combined-liver-and-kidney-transplant-a-case-report
#10
Thanzeela Kausar Mohideen, Hong Wu
Calcineurin inhibitors are imperative in the success of a transplanted organ. However, these immunosuppressants can lead to a rare complication known as calcineurin inhibitor induced pain syndrome (CIPS), which may not be recognized early and managed appropriately. We present a case of a 35-year-old female who underwent a combined liver/kidney transplant and developed lower extremity pain while being maintained on tacrolimus. This case illustrates a patient with previously reported characteristic clinical features of CIPS in addition to uncharacteristic neuropathic symptoms and imaging findings...
September 4, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28882100/low-dose-cyclosporine-in-treatment-of-membranous-nephropathy-with-nephrotic-syndrome-effectiveness-and-renal-safety
#11
Xiaojuan Yu, Lin Ruan, Zhen Qu, Zhao Cui, Yimiao Zhang, Xin Wang, Liqiang Meng, Xiaojing Liu, Fang Wang, Ying Zhang, Gang Liu, Li Yang
BACKGROUND: To observe effectiveness and renal safety of long-term low-dose cyclosporine in idiopathic membranous nephropathy (IMN). METHODS: Sixty-eight patients were enrolled in this prospective cohort study. Renal endpoint was defined as a decrease in eGFR ≥50% from baseline and a development of eGFR ≤60 ml/min/1.73m(2). RESULTS: A cyclosporine dose of 2.0 ± 0.5 mg/kg/d and a prednisone of 0.3 ± 0.2 mg/kg/d were prescribed...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28879428/difficult-to-treat-idiopathic-nephrotic-syndrome-established-drugs-open-questions-and-future-options
#12
REVIEW
Markus J Kemper, Lisa Valentin, Michael van Husen
The idiopathic nephrotic syndrome in childhood can be classified according to the International Study of Kidney Disease in Children (ISKDC) based on the response to steroids. Typically, steroid-sensitive nephrotic syndrome (SSNS) is characterised by minimal changes in disease (MCD) histology, whereas in steroid-resistant nephrotic syndrome (SRNS) focal segmental glomerulosclerosis (FSGS) is the most prevalent lesion. Patients with SSNS may develop frequent relapses and/or steroid dependency, which can be difficult to treat...
September 6, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28878864/use-of-everolimus-in-liver-transplantation
#13
REVIEW
Mei-Ling Yee, Hui-Hui Tan
In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation (LT) setting. The efficacy of everolimus (EVR) in de novo LT is established and a reasonable time to initiate EVR is 30 d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor (CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy...
August 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28864927/cost-analysis-on-the-use-of-rituximab-and-calcineurin-inhibitors-in-children-and-adolescents-with-steroid-dependent-nephrotic-syndrome
#14
Franca Iorember, Diego Aviles, Mahmoud Kallash, Oluwatoyin Bamgbola
BACKGROUND: Rituximab (RTX) is increasingly being used in place of calcineurin inhibitors (CNI) in pediatric patients with steroid-dependent nephrotic syndrome (SDNS). However, despite its favorable safety profile, its unit cost is prohibitive. We therefore compared the healthcare costs associated with the use of both agents in a retrospective cohort. METHODS: This study was a retrospective analysis of data retrieved from the medical charts and electronic databases of pediatric patients (age range 2-18 years) with SDNS who were treated with either CNI or RTX from January 2008 to December 2012 at Children's Hospital of New Orleans, Louisiana...
September 1, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28863192/e2-er-%C3%AE-inhibit-iso-induced-cardiac-cellular-hypertrophy-by-suppressing-ca2-calcineurin-signaling
#15
Cheng-Yen Tsai, Wei-Wen Kuo, Marthandam Asokan Shibu, Yueh-Min Lin, Chien-Nam Liu, Yi-Hui Chen, Cecilia-Hsuan Day, Chia-Yao Shen, Vijaya Padma Viswanadha, Chih-Yang Huang
Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17β-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this study we have determined the effect of E2/ERβ against ISO induced cellular hypertrophy in H9c2 cardiomyoblast cells. The results confirm that ISO induced cardiac-hypertrophy by elevating the levels of hypertrophy associated proteins, ANP and BNP and further by upregulating p-CaMKII, calcineurin, p-GATA4 and NFATc3 which was correlated with a significant enlargement of the H9c2 cardiomyoblast...
2017: PloS One
https://www.readbyqxmd.com/read/28861617/novel-therapeutic-approaches-to-atopic-dermatitis
#16
REVIEW
Katarzyna Osinka, Karolina Dumycz, Bartłomiej Kwiek, Wojciech Feleszko
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. The number of people affected by AD is relatively high and seems to be rising. Although mild and moderate forms of the disease can be well controlled by the use of emollients, topical corticosteroids, and topical calcineurin inhibitors, treatment of severe is still a huge challenge. The new hope is biologic drugs, magic bullets in allergy, targeted at different points of the complex pathomechanism of inflammation in AD. In this review, novel biologic therapies are discussed, including recombinant monoclonal antibodies directed against various interleukin pathways (such as IL-4, IL-13, TSLP, IL-31, and IL-12/23), on immunoglobulin E, molecules acting as T cells, B cells, etc...
August 31, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28857712/a-novel-drug-interaction-between-busulfan-and-blinatumomab
#17
Karen Sweiss, John G Quigley, Annie Oh, Jonathan Lee, Rosa Ye, Damiano Rondelli, Pritesh Patel
Busulfan is an alkylating agent used in pre-transplant conditioning for patients undergoing hematopoietic stem cell transplantation. Several factors contribute to variations in busulfan drug disposition including bioavailability, age, liver function, genetic polymorphisms, and concurrent administration of other drugs. Busulfan is metabolized by hepatic oxidation via the cytochrome P450 3A4 system as well as through conjugation with glutathione. Interactions with drugs such as phenytoin, itraconazole, and metronidazole have been reported to alter busulfan clearance and result in sub- or supra-therapeutic concentrations...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28856745/using-known-drug-interactions-to-manage-supratherapeutic-calcineurin-inhibitor-concentrations
#18
REVIEW
Nicholas W Lange, David M Salerno, Karen Berger, Demetra S Tsapepas
OBJECTIVES: To summarize the available body of evidence guiding the management of supratherapeutic concentrations of calcineurin inhibitors (CNI) using cytochrome P450 (CYP450) enzyme inducers. METHODS: A non-date restricted literature search within MEDLINE, Embase, and Scopus was performed using the terms "cyclosporine", "tacrolimus", "calcineurin inhibitor", "toxicity", "pharmacokinetics", "carbamazepine", "rifampin", "phenytoin", and "phenobarbital." Additional references were identified from a review of all included citations...
August 30, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28846737/immunosuppressant-prescription-pattern-and-trend-in-kidney-transplantation-a-multicenter-study-in-korea
#19
Ji-Yeun Chang, Jihyun Yu, Byung Ha Chung, Jaeseok Yang, Sung-Joo Kim, Chan-Duck Kim, Sang-Ho Lee, Jong Soo Lee, Joong Kyung Kim, Cheol Woong Jung, Chang Kwon Oh, Chul Woo Yang
BACKGROUND: The actual prescription pattern of immunosuppressive agents in kidney transplantation is unclear. METHODS: We investigated the pattern and trend of immunosuppressive treatment for kidney transplant patients in South Korea. A total of 636 patients at nine transplant centers were enrolled and followed for one year. We reviewed medical records and evaluated induction therapy, as well as the changing pattern and cause of maintenance therapy. RESULTS: Most patients (n = 621, 97...
2017: PloS One
https://www.readbyqxmd.com/read/28844947/outcome-of-second-transplantation-using-umbilical-cord-blood-for-graft-failure-after-allogeneic-hematopoietic-stem-cell-transplantation-for-aplastic-anemia
#20
Yasushi Onishi, Takehiko Mori, Shinichi Kako, Hideo Koh, Naoyuki Uchida, Tadakazu Kondo, Takeshi Kobayashi, Hiromasa Yabe, Toshihiro Miyamoto, Koji Kato, Ritsuro Suzuki, Shinji Nakao, Hirohito Yamazaki
Graft failure (GF) is the most critical life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia, for which a second transplantation would be the only effective treatment. However, optimal transplant procedures have not been established for the second transplantation in this setting. The outcome of 22 patients with aplastic anemia, aged ≥16 years, who underwent umbilical cord blood transplantation for GF after the first HSCT, was retrospectively analyzed using the registry database of the Japan Society for Hematopoietic Cell Transplantation...
August 24, 2017: Biology of Blood and Marrow Transplantation
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