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https://www.readbyqxmd.com/read/29149976/clinical-challenges-of-tacrolimus-for-maintenance-immunosuppression-post-lung-transplantation
#1
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/29146214/-treatments-of-steroid-dependent-nephrotic-syndrome-in-children
#2
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/29143318/calcineurin-inhibitor-induced-complement-system-activation-via-erk1-2-signalling-is-inhibited-by-socs-3-in-human-renal-tubule-cells
#3
Beatrix Loeschenberger, Lea Niess, Reinhard Würzner, Hubert Schwelberger, Iris E Eder, Martin Puhr, Julia Guenther, Jakob Troppmair, Michael Rudnicki, Hannes Neuwirt
One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations...
November 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29136616/no-relapse-of-calcineurin-inhibitor-associated-thrombotic-microangiopathy-after-discontinuation-of-eculizumab
#4
Thomas Neumann, Andrzej Plis, Martin Weigel, Sylvia Stracke, Sigrun Friesecke, Stephanie-Susanne Stecher, Laila Schneidewind, Christoph Busemann, Christian Andreas Schmidt, William H Krüger
No abstract text is available yet for this article.
November 15, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/29135018/chronic-prurigo-of-nodular-type-a-review
#5
Claudia Zeidler, Athanasios Tsianakas, Manuel Pereira, Hartmut Ständer, Gil Yosipovitch, Sonja Ständer
Prurigo nodularis (PN) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed, hyperkeratotic and intensively itching papules and nodules. PN evolves along with chronic pruritus in the context of diverse dermatological, systemic, neurological or psychiatric conditions. Permanent scratching is possibly a major trigger of PN, although its exact pathophysiology remains unclear. Current state-of-the-art therapy for PN consists of topical steroids, capsaicin, calcineurin inhibitors, ultraviolet (UV) therapy, systemic administration of gabapentinoids, μ-opioid receptor antagonists, antidepressants or immunosuppressants...
August 23, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29133357/myeloid-derived-suppressor-cells-ameliorate-cyclosporine-a-induced-hypertension-in-mice
#6
Valorie L Chiasson, Kelsey R Bounds, Piyali Chatterjee, Lochana Manandhar, Abhinandan R Pakanati, Marcos Hernandez, Bilal Aziz, Brett M Mitchell
The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice...
November 13, 2017: Hypertension
https://www.readbyqxmd.com/read/29131070/pathophysiology-of-post-transplant-hypertension-in-kidney-transplant-focus-on-calcineurin-inhibitors-induced-oxidative-stress-and-renal-sodium-retention-and-implications-with-rhoa-rho-kinase-pathway
#7
Lorenzo A Calò, Verdiana Ravarotto, Francesca Simioni, Elena Naso, Francesco Marchini, Luciana Bonfante, Lucrezia Furian, Paolo Rigotti
Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule...
October 16, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29130583/endoscopic-retrograde-cholangio-pancreatography-in-the-management-of-biliary-complications-after-paediatric-liver-transplantation
#8
Sivaramakrishnan Venkatesh Karthik, Seng-Hock Quak, Marion M Aw
BACKGROUND: The published paediatric experience with Endoscopic retrograde cholangio-pancreatography (ERCP) in the diagnosis and management of biliary complications following liver transplantation (LT) is limited. AIMS: We describe our experience with ERCP in the management of children following LT who presented with biliary complications, over a 20 year period (1995-2014). METHODS: The retrospectively reviewed data is summarized descriptively...
November 11, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29129208/augmented-gene-expression-triggered-by-na-k-atpase-inhibition-role-of-ca-2-i-mediated-and-independent-excitation-transcription-coupling
#9
Larisa V Smolyaninova, Svetlana V Koltsova, Svetlana V Sidorenko, Sergei N Orlov
In rat vascular smooth muscle cells (RVSMC), 3-h Na(+),K(+)-ATPase inhibition by ouabain or in K(+)-free medium resulted in the inversion of the [Na(+)]i/[K(+)]i ratio and elevation up to 7-fold the content of Egr1, Atf3, Nr4a1 and Ptgs2 mRNAs. Ouabain increased the rate of 45Ca(2+) influx by 2-fold that was abolished by L-type voltage-gated Ca(2+) channel blocker nicardipine, but it was resistant to Na(+)/Ca(2+) exchanger inhibitor KB-R7943. To study the role of Ca(2+)-mediated signaling in the expression of Na(+)i/K(+)i-sensitive genes we used intracellular Ca(2+) chelator BAPTA and incubated RVSMC in Ca(2+)-free medium...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29124712/safety-and-efficacy-of-phototherapy-in-the-management-of-eczema
#10
Annalisa Patrizi, Beatrice Raone, Giulia Maria Ravaioli
Atopic Dermatitis (AD), a common skin disease, can occur in patients of all age, gender and ethnicity. It is an inflammatory affection, characterized by chronic and highly debilitating behavior. First-line interventions against AD include environmental measures and topical emollients, corticosteroids or calcineurin inhibitors. When these measures are not sufficient, phototherapy represents an efficient second-line option of treatment; it can be administered on its own, or in the most severe cases combined with systemic medicaments such as corticosteroids...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29124708/phototherapy-in-atopic-dermatitis
#11
José María Ortiz-Salvador, Amparo Pérez-Ferriols
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Currently management of AD includes avoidance of triggering factors, skin care aiming to compensate the skin barrier defects, anti-inflammatory therapy (mostly topical corticosteroids and topical calcineurin inhibitors). When these first-line approaches are unsuccessful, systemic treatment or phototherapy ought to be carried out as next line of defence. Current phototherapy modalities for AD include broadband UVB (290-320 nm), narrowband UVB (311-313 nm), UVA-1 therapy (340-400 nm), UVA therapy plus 8-methoxypsoralens (PUVA), 308 nm excimer laser (EL) and Full spectrum light (FSL)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29111569/the-influence-of-immunosuppressants-on-direct-acting-antiviral-therapy-is-dependent-on-hepatitis-c-virus-genotype
#12
Alexandra Frey, Katja Piras-Straub, Andreas Walker, Jörg Timm, Guido Gerken, Kerstin Herzer
BACKGROUND: Direct-acting antivirals (DAA) have substantially increased sustained virological response rates after liver transplantation, with improved tolerance compared to interferon-based therapy. The influence of immunosuppressive agents on the efficacy of DAAs has not been clarified. METHODS: Subgenomic HCV replicons for genotype (GT) 1b, 2b, 3a and 4a were treated with the mammalian target of rapamycin (mTOR) inhibitors everolimus and sirolimus or with the calcineurin inhibitors (CNI) cyclosporine or tacrolimus, either alone or in combination with selected DAAs...
November 7, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29110799/acute-postoperative-management-after-lung-transplantation
#13
REVIEW
Christopher Potestio, Desmond Jordan, Bessie Kachulis
Despite many advances in the field of lung transplantation, lung transplant recipients have the lowest median survival of any solid organ transplant population. Complications such as reperfusion injury, graft rejection, infection, and anastomotic breakdown increase morbidity and mortality during the immediate postoperative period. Ventilator management with lung protective strategies can not only minimize ventilator time and mitigate the risk of ventilator-associated pneumonia, but it may also decrease the risk of primary graft dysfunction and graft failure...
June 2017: Best Practice & Research. Clinical Anaesthesiology
https://www.readbyqxmd.com/read/29106654/the-population-level-costs-of-immunosuppression-medications-for-the-treatment-of-glomerulonephritis-are-increasing-over-time-due-to-changing-patterns-of-practice
#14
Sean Barbour, Clifford Lo, Gabriela Espino-Hernandez, Sharareh Sajjadi, John Feehally, Scott Klarenbach, Jagbir Gill
Background: Immunosuppression (IS) is the main treatment for most types of glomerulonephritis (GN). Quantifying the cost of IS is necessary to ensure equitable access to therapies and optimal health outcomes, but the real-world cost of IS treatment for GN is largely unknown. We examined temporal changes in the population-level IS medication costs for GN over a 14-year period in a large Canadian province. Methods: We linked a provincial pathology database (containing all GN cases from 2000 to 2012) with renal and medication administrative databases to capture clinical characteristics and IS medications, with follow-up until 2013...
July 2, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29101238/glucocorticoid-resistance-is-reverted-by-lck-inhibition-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#15
Valentina Serafin, Giorgia Capuzzo, Gloria Milani, Sonia Anna Minuzzo, Marica Pinazza, Roberta Bortolozzi, Silvia Bresolin, Elena Porcù, Chiara Frasson, Stefano Indraccolo, Giuseppe Basso, Benedetta Accordi
Pediatric T-acute lymphoblastic leukemia (T-ALL) patients often display resistance to glucocorticoid (GC) treatment. These patients, classified as Prednisone Poor Responders (PPR), have poorer outcome compared to the other pediatric T-ALL patients receiving a high-risk adapted therapy. Since glucocorticoids are administered to ALL patients during all the different phases of therapy, GC resistance represents an important challenge to be addressed in order to improve the outcome for these patients. Mechanisms underlying resistance are not yet fully unraveled, thus our research focused on the identification of deregulated signaling pathways to point out new targeted approaches...
November 3, 2017: Blood
https://www.readbyqxmd.com/read/29096030/tacrolimus-a-review-of-laboratory-detection-methods-and-indications-for-use
#16
Derick A Kalt
Tacrolimus (Tac) is an immunosuppressive drug that is used in preventing organ and tissue rejection in patients after transplantation. Tac administration requires frequent and diligent monitoring by physicians to ensure proper dosage and to limit the potential for harmful adverse effects, which can include renal damage, neurotoxicity, and other serious adverse events. Tac is a calcineurin inhibitor, which suppresses the function of T-cells. Its success as an immunosuppressive agent has been well documented in preventing graft-vs-host disease in several types of organ transplants...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29091890/the-effect-of-clinically-relevant-doses-of-immunosuppressive-drugs-on-human-mesenchymal-stem-cells
#17
Eliska Javorkova, Julie Vackova, Michaela Hajkova, Barbora Hermankova, Alena Zajicova, Vladimir Holan, Magdalena Krulova
Immunosuppressive drugs are used to suppress graft rejection after transplantation and for the treatment of various diseases. The main limitations of their use in clinical settings are severe side effects, therefore alternative approaches are desirable. In this respect, mesenchymal stem cells (MSCs) possess a regenerative and immunomodulatory capacity that has generated considerable interest for their use in cell-based therapy. Currently, MSCs are tested in many clinical trials, including the treatment of diseases which require simultaneous immunosuppressive treatment...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29079427/correlation-and-cluster-analysis-of-immunomodulatory-drugs-based-on-cytokine-profiles
#18
Fredrik K Wallner, Malin Hultquist Hopkins, Nina Woodworth, Therese Lindvall Bark, Peter Olofsson, Andreas Tilevik
Drug discovery is a constant struggle to overcome hurdles posed by the complexity of biological systems. One of these hurdles is to find and understand the molecular target and the biological mechanism of action. Although the molecular target has been determined, the true biological effect may be unforeseen also for well-established drugs. Hence, there is a need for novel ways to increase the knowledge of the biological effects of drugs in the developmental process. In this study, we have determined cytokine profiles for 26 non-biological immunomodulatory drugs or drug candidates and used these profiles to cluster the compounds according to their effect in a preclinical ex vivo culture model of arthritis...
October 25, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29077654/improved-pulse-wave-velocity-and-renal-function-in-individualized-calcineurin-inhibitor-treatment-by-immunomonitoring-the-randomized-controlled-calcineurin-inhibitor-sparing-cis-trial
#19
Claudia Sommerer, Janina Brocke, Thomas Bruckner, Matthias Schaier, Christian Morath, Stefan Meuer, Martin Zeier, Thomas Giese
BACKGROUND: A new immune monitoring tool which assesses the expression of nuclear factor of activated T-cells (NFAT)-regulated genes measures the functional effects of cyclosporine A. This is the first prospective randomized controlled study to compare standard pharmacokinetic monitoring by cyclosporine trough levels to NFAT-regulated gene expression (NFAT-RE). METHODS: Expression of the NFAT-regulated genes was determined by qRT-PCR at cyclosporine trough and peak level...
October 26, 2017: Transplantation
https://www.readbyqxmd.com/read/29073235/src-family-kinases-negatively-regulate-nfat-signaling-in-resting-human-t-cells
#20
Alan Baer, Winston Colon-Moran, Jinhua Xiang, Jack T Stapleton, Nirjal Bhattarai
T cell signaling is required for activation of both natural and therapeutic T cells including chimeric antigen receptor (CAR) T cells. Identification of novel factors and pathways regulating T cell signaling may aid in development of effective T cell therapies. In resting human T cells, the majority of Src-family of tyrosine kinases (SFKs) are inactive due to phosphorylation of a conserved carboxy-terminal tyrosine residue. Recently, a pool of enzymatically active SFKs has been identified in resting T cells; however, the significance of these is incompletely understood...
2017: PloS One
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