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Calcineurin inhibitors

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https://www.readbyqxmd.com/read/28533501/post-transplant-diabetes-mellitus-after-kidney-transplant-in-hispanics-and-caucasians-treated-with-tacrolimus-based-immunosuppression
#1
Pedro W Baron, Sergio Infante, Regina Peters, Jerusalem Tilahun, Jill Weissman, Lauren Delgado, Arputharaj Higgins Kore, W Lawrence Beeson, Michael E de Vera
BACKGROUND Development of post-transplant diabetes mellitus after kidney transplant (PTDM) significantly increases kidney graft loss and mortality. Several risk factors for PTDM have been reported, including Hispanic ethnicity and the use of calcineurin inhibitors and corticosteroids. The incidence and impact of PTDM in the Hispanic kidney transplant population is unknown. MATERIAL AND METHODS We retrospectively reviewed the medical records of 155 Hispanic and 124 Caucasian patients, who were not diabetics and underwent kidney transplant between January 2006 and December 2011...
May 23, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28525959/challenges-and-opportunities-in-targeting-the-cd28-ctla-4-pathway-in-transplantation-and-autoimmunity
#2
Rebecca L Crepeau, Mandy L Ford
Introduction T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. Areas Covered This review discusses past, current and future biological therapies that have been utilized to block the CD28/CTLA-4 cosignaling pathway in the settings of autoimmunity and transplantation, as well the challenges facing successful implementation of these therapies...
May 19, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28523792/the-impact-of-calcineurin-inhibitors-on-neutrophil-gelatinase-associated-lipocalin-and-fibroblast-growth-factor-23-in-long-term-kidney-transplant-patients
#3
Inger Hjørdis Bleskestad, Inga Strand Thorsen, Grete Jonsson, Øyvind Skadberg, Lasse Gunnar Gøransson
BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), a protein with bacteriostatic functions rapidly excreted from stimulated or damaged epithelial cells, is elevated in acute and chronic kidney disease. A calcineurin dependent signaling pathway for fibroblast growth factor 23 (FGF23) has been revealed, but the effect of calcineurin inhibitors (CNIs) on the levels of NGAL and markers of mineral metabolism in long-term kidney transplant patients has not been explored. METHODS: In a cross-sectional study, 39 patients who received a first kidney transplant more than 10 years ago were split into two groups based on whether (n=28) or not (n=11) they used CNIs...
May 19, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28516402/effects-of-calcineurin-inhibitors-on-sodium-excretion-in-recipients-of-allogeneic-hematopoietic-stem-cell-transplantation
#4
Masuho Saburi, Sumiko Kohashi, Jun Kato, Yuya Koda, Masatoshi Sakurai, Takaaki Toyama, Taku Kikuchi, Daiki Karigane, Sayako Yuda, Yusuke Yamane, Risa Hashida, Ryohei Abe, Tomonori Nakazato, Junichi Hirahashi, Masao Ogata, Shinichiro Okamoto, Takehiko Mori
Calcineurin inhibitors (CIs) such as cyclosporine A (CSA) and tacrolimus often cause renal dysfunction, resulting in increased serum creatinine, hyperkalemia, and hyperuricemia. However, the effects of CIs on sodium excretion have not been fully elucidated. We retrospectively evaluated the effects of CI administration on sodium excretion in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Fifty consecutive recipients each of allogeneic HSCT receiving either CSA or tacrolimus (100 patients in total) with available data for weekly fractional excretion of sodium (FENa) for a 4-week period after transplantation were enrolled in this retrospective analysis...
May 17, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28508573/regional-differences-in-the-management-and-outcome-of-kidney-transplantation-in-patients-with-human-immunodeficiency-virus-infection-a-3-year-retrospective-cohort-study
#5
Marina P Cristelli, Federico Cofán, Helio Tedesco-Silva, Joan Carles Trullàs, Daniel Wagner C L Santos, Cristian Manzardo, Fernando Agüero, Asunción Moreno, Federico Oppenheimer, Fritz Diekmann, Jose O Medina-Pestana, Jose Maria Miro
BACKGROUND: In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES: We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS: This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT...
May 16, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
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
#6
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
#7
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/28503959/emerging-drugs-for-prevention-of-t-cell-mediated-rejection-in-liver-and-kidney-transplantation
#8
Tiffany Cl Wong, Chung-Mau Lo, James Yy Fung
Acute and chronic graft rejection continues to be an important problem after solid organ transplantation. With the introduction of potent immunosuppressive agents such as calcineurin inhibitors, the risk of rejection has been significantly reduced. However, the adverse effects of life-long immunosuppression remain a concern, and there exist a fine balance between over-immunosuppression and risk of rejection. Areas covered. In this review, the current standard of care in immunosuppressive therapy, including the use of steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of rapamycin inhibitors, will be discussed...
May 15, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28500071/activated-microglia-desialylate-and-phagocytose-cells-via-neuraminidase-galectin-3-and-mer-tyrosine-kinase
#9
Koji Nomura, Anna Vilalta, David H Allendorf, Tamara C Hornik, Guy C Brown
Activated microglia can phagocytose dying, stressed, or excess neurons and synapses via the phagocytic receptor Mer tyrosine kinase (MerTK). Galectin-3 (Gal-3) can cross-link surface glycoproteins by binding galactose residues that are normally hidden below terminal sialic acid residues. Gal-3 was recently reported to opsonize cells via activating MerTK. We found that LPS-activated BV-2 microglia rapidly released Gal-3, which was blocked by calcineurin inhibitors. Gal-3 bound to MerTK on microglia and to stressed PC12 (neuron-like) cells, and it increased microglial phagocytosis of PC12 cells or primary neurons, which was blocked by inhibition of MerTK...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28498905/basiliximab-for-posterior-reversible-encephalopathy-syndrome-after-lung-transplantation
#10
Hiroya Yamagishi, Toyofumi F Chen-Yoshikawa, Hiroshi Date
Posterior reversible encephalopathy syndrome is a neurological complication associated with calcineurin inhibitors. There is no consensus regarding the continuation of calcineurin inhibitors in the event of posterior reversible encephalopathy syndrome. We report 3 cases of posterior reversible encephalopathy syndrome among 155 lung transplant recipients (1.9%). The calcineurin inhibitor trough level exceeded the therapeutic range in only 1 case. Our findings demonstrate that temporary cessation of calcineurin inhibitors and administration of basiliximab may be effective strategies for managing posterior reversible encephalopathy syndrome...
May 12, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28495529/mek-erk-and-calcineurin-nfat-mediated-mechanism-of-cerebral-hyperemia-and-brain-injury-following-nmda-receptor-activation
#11
Yuki Kurauchi, Rintaro Kinoshita, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara, Kunio Ishii
N-methyl-d-aspartate (NMDA) receptor activation increases regional cerebral blood flow (rCBF) and induces neuronal injury, but similarities between these processes are poorly understood. In this study, by measuring rCBF in vivo, we identified a clear correlation between cerebral hyperemia and brain injury. NMDA receptor activation induced brain injury as a result of rCBF increase, which was attenuated by an inhibitor of mitogen-activated protein kinase or calcineurin. Moreover, NMDA induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear translocation of nuclear factor of activated T-cell (NFAT) in neurons...
May 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28487836/allergic-conjunctivitis-in-asia
#12
REVIEW
Bernard Yu-Hor Thong
Allergic conjunctivitis (AC), which may be acute or chronic, is associated with rhinitis in 30%-70% of affected individuals, hence the term allergic rhinoconjunctivitis (AR/C). Seasonal and perennial AC is generally milder than the more chronic and persistent atopic and vernal keratoconjunctivitis. Natural allergens like house dust mites (HDM), temperate and subtropical grass and tree pollen are important triggers that drive allergic inflammation in AC in the Asia-Pacific region. Climate change, environmental tobacco smoke, pollutants derived from fuel combustion, Asian dust storms originating from central/north Asia and phthalates may also exacerbate AR/C...
April 2017: Asia Pacific Allergy
https://www.readbyqxmd.com/read/28478972/long-term-management-of-moderate-to-severe-atopic-dermatitis-with-dupilumab-and-concomitant-topical-corticosteroids-liberty-ad-chronos-a-1-year-randomised-double-blinded-placebo-controlled-phase-3-trial
#13
Andrew Blauvelt, Marjolein de Bruin-Weller, Melinda Gooderham, Jennifer C Cather, Jamie Weisman, David Pariser, Eric L Simpson, Kim A Papp, H Chih-Ho Hong, Diana Rubel, Peter Foley, Errol Prens, Christopher E M Griffiths, Takafumi Etoh, Pedro Herranz Pinto, Ramon M Pujol, Jacek C Szepietowski, Karel Ettler, Lajos Kemény, Xiaoping Zhu, Bolanle Akinlade, Thomas Hultsch, Vera Mastey, Abhijit Gadkari, Laurent Eckert, Nikhil Amin, Neil M H Graham, Gianluca Pirozzi, Neil Stahl, George D Yancopoulos, Brad Shumel
BACKGROUND: Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis...
May 4, 2017: Lancet
https://www.readbyqxmd.com/read/28476075/drugs-for-discoid-lupus-erythematosus
#14
REVIEW
Sue Jessop, David A Whitelaw, Matthew J Grainge, Prativa Jayasekera
BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus, which can cause scarring. Many drugs have been used to treat this disease and some (such as thalidomide, cyclophosphamide and azathioprine) are potentially toxic. This is an update of a Cochrane Review first published in 2000, and previously updated in 2009. We wanted to update the review to assess whether any new information was available to treat DLE, as we were still unsure of the effectiveness of available drugs and how to select the most appropriate treatment for an individual with DLE...
May 5, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28469160/differential-roles-for-six-p-type-calcium-atpases-in-sustaining-intracellular-ca-2-homeostasis-asexual-cycle-and-environmental-fitness-of-beauveria-bassiana
#15
Jie Wang, Xiao-Guan Zhu, Sheng-Hua Ying, Ming-Guang Feng
A global insight into the roles of multiple P-type calcium ATPase (CA) pumps in sustaining the life of a filamentous fungal pathogen is lacking. Here we elucidated the functions of five CA pumps (Eca1, Spf1 and PmcA/B/C) following previous characterization of Pmr1 in Beauveria bassiana, a fungal insect pathogen. The fungal CA pumps interacted at transcriptional level, at which singular deletions of five CA genes depressed eca1 expression by 76-98% and deletion of spf1 resulted in drastic upregulation of four CA genes by 36-50-fold...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28466423/chronic-pruritus-current-and-emerging-treatment-options
#16
REVIEW
Manuel P Pereira, Sonja Ständer
Chronic pruritus remains a central societal issue because of its high occurrence and the substantial decrease in quality of life it may cause to affected individuals. Not only dermatological conditions, but also systemic, neurological, or psychiatric diseases may lead to chronic pruritus. Additionally, various underlying conditions may coexist or the cause may be unknown. Due to its heterogeneity, the therapeutic approach is complex and remains a challenge for the clinician. Basic measures such as emollients to avoid xerosis and treatment of the underlying disease should be initiated regardless of the duration of the symptom...
June 2017: Drugs
https://www.readbyqxmd.com/read/28465499/posterior-reversible-encephalopathy-syndrome-after-orthotopic-heart-transplantation-a-case-report
#17
Rigoberto Ramirez, Preetham Reddy Muskula, Mark P Everley
BACKGROUND Calcineurin inhibitor-induced posterior reversible encephalopathy syndrome (PRES) is well described in liver and kidney transplant patients, but there is a paucity of data in heart transplant patients. PRES syndrome in the setting of heart transplantation can occur as early as 5 days following transplantation. CASE REPORT A 32-year-old woman who had recently undergone orthotopic heart transplantation developed headaches, visual disturbances, and generalized tonic clonic seizures 5 days after initiating anti-rejection therapy (tacrolimus, mycophenolate, and prednisone)...
May 3, 2017: American Journal of Case Reports
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
#18
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/28461770/pimecrolimus-increases-the-melanogenesis-and-migration-of-melanocytes-in-vitro
#19
Ping Xu, Jie Chen, Cheng Tan, Ren-Sheng Lai, Zhong-Sheng Min
Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro...
May 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28460546/an-update-on-chemical-pharmacotherapy-options-for-the-prevention-of-kidney-transplant-rejection-with-a-focus-on-costimulation-blockade
#20
Florian Kälble, Matthias Schaier, Sebastian Schäfer, Caner Süsal, Martin Zeier, Claudia Sommerer, Christian Morath
The introduction of calcineurin inhibitors (CNI) has greatly improved graft survival in the past three decades. However, long-term graft survival is still limited due to chronic allograft injury and side-effects of immunosuppressive medication. Areas covered: The present overview gives an update on pharmacotherapeutic strategies after kidney transplantation. The main focus is on CNI-sparing regimens using co-stimulatory blockade and on new substances on the horizone. Expert opinion: CNI sparing regimens are well-established...
June 2017: Expert Opinion on Pharmacotherapy
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