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Calcineurin

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https://www.readbyqxmd.com/read/28214069/-pharmacokinetic-drug-interaction-between-miconazole-mucoadhesive-tablet-and-tacrolimus-about-3%C3%A2-case-reports-in-transplant-patients
#1
Marion Lepelley, Sophie Logerot, Xavier Fonrose, Céline Villier
Loramyc(®) is a mucoadhesive tablet of miconazole, indicated for the treatment of oropharyngeal candidiasis in immunocompromised patients. Miconazole, as others azole antifungals, is known for its potent inhibitory properties of cytochromes P450 enzymes and P-glycoprotein (P-gp). Inhibition of cytochromes P450 enzymes and P-gp can produce pharmacokinetic drug interaction. Immunosuppressive agents, such as calcineurin inhibitors (tacrolimus, cyclosporine) are substrates of cytochromes P450 3A4 and P-gp. Nevertheless, the impact of systemic absorption of miconazole mucoadhesive tablet has not been investigated by the laboratory before regulatory approval...
January 12, 2017: Thérapie
https://www.readbyqxmd.com/read/28207493/treatment-of-lupus-nephritis-current-paradigms-and-emerging-strategies
#2
Maria Dall'Era
PURPOSE OF REVIEW: Lupus nephritis is the most common organ-threatening manifestation of lupus and continues to result in end-stage renal disease. This review describes the contemporary treatment of lupus nephritis as well as emerging therapeutic strategies. RECENT FINDINGS: Lupus nephritis management consists of an initial (induction) phase and a maintenance (extended) phase in which steroids are used in combination with another immunosuppressive medication. Current treatments are incompletely effective and associated with substantial toxicity...
February 15, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28203051/a-review-and-update-on-orphan-drugs-for-the-treatment-of-noninfectious-uveitis
#3
REVIEW
Caiyun You, Haitham F Sahawneh, Lina Ma, Buraa Kubaisi, Alexander Schmidt, C Stephen Foster
INTRODUCTION: Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT) drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as "orphan drugs" and are widely used for systemic autoimmune diseases or organ transplantation...
2017: Clinical Ophthalmology
https://www.readbyqxmd.com/read/28196514/defining-the-contribution-of-neuroinflammation-to-parkinson-s-disease-in-humanized-immune-system-mice
#4
Gunjan Dhawan Manocha, Angela Marie Floden, Kendra Lynn Puig, Kumi Nagamoto-Combs, Clemens R Scherzer, Colin Kelly Combs
BACKGROUND: Reactive microglia have been associated with the histological changes that occur in Parkinson's disease brains and mouse models of the disease. Multiple studies from autopsy brains have verified the presence of microgliosis in several brain regions including substantia nigra, striatum, hippocampus and various cortical areas. MPTP injections in rodents have also shown striato-nigral microgliosis correlating with the loss of dopaminergic neurons. However, consistent data with respect to cytokine and immune cell changes during Parkinson's disease have not been fully defined...
February 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28196317/common-skin-conditions-in-children-noninfectious-rashes
#5
Brian Z Rayala, Dean S Morrell
Cutaneous adverse drug reactions are among the most common noninfectious rashes of childhood. Cutaneous adverse drug reactions are classified as morbilliform, urticarial, bullous, pustular, or psoriasiform. Atopic dermatitis is one of the most common inflammatory cutaneous eruptions, and is characterized by pruritus and flexural distribution. Emollients and topical corticosteroids are first-line therapies. Topical calcineurin inhibitors are second-line, steroid-sparing drugs for certain conditions, such as face and eyelid eczema...
February 2017: FP Essentials
https://www.readbyqxmd.com/read/28195062/the-influence-of-the-tumor-necrosis-factor-alpa-308g-a-polymorphism-on-the-efficacy-of-immunosuppressive-therapy-in-patients-after-kidney-transplantation
#6
M M Kotowski, A Bogacz, J Bartkowiak-Wieczorek, J Sienko, D Procyk, K Dziewanowski, M Ostrowski, B Czerny, E Grzeskowiak, B Machalinski
Cytokines play an important role in the immune response. The calcineurin inhibitors (cyclosporine CsA, tacrolimus TAC) widely used after renal transplantation to prevent allograft rejection are immunosuppressive drugs suppressing the production of cytokines. These drugs are characterized by interindividual variability and require monitoring their blood concentrations to predict their optimal dosage. Therefore, the aim of the study was to determine the correlation between therapeutic effects of immunosuppressants and the tumor necrosis factor-α (TNF-α)-308G>A polymorphism in renal transplant patients...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28194557/-4z-15z-octadecadienoic-acid-inhibits-glycogen-synthase-kinase-3%C3%AE-and-glucose-production-in-h4iie-cells
#7
Jun Yoshida, Shota Uesugi, Tetsuaki Kawamura, Ken-Ichi Kimura, Dawei Hu, Shuang Xia, Naoki Toyooka, Masao Ohnishi, Hideki Kawashima
Many uncommon non-methylene-interrupted fatty acids (NMI FA) are present in limpet gonads, but their biological properties remain unknown. To investigate new biological effects of naturally occurring NMI FA in eukaryotic cells, the biological activities of structurally analogous (4Z,15Z)-octadecadienoic acid (1), (9Z,20Z)-tricosadienoic acid (2), and (12Z,23Z)-hexacosadienoic acid (3) were examined by using a yeast-based drug-screening system using the Ca(2+)-sensitive mutant strain, Saccharomyces cerevisiae (zds1Δ erg3Δ pdr1Δ pdr3Δ)...
February 13, 2017: Lipids
https://www.readbyqxmd.com/read/28193247/efficacy-and-safety-of-calcineurin-inhibitor-treatment-for-iga-nephropathy-a-meta-analysis
#8
Yu-Huan Song, Guang-Yan Cai, Yue-Fei Xiao, Yi-Ping Wang, Bao-Shi Yuan, Yuan-Yuan Xia, Si-Yang Wang, Pu Chen, Shu-Wen Liu, Xiang-Mei Chen
BACKGROUND: IgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide. Calcineurin inhibitors (CNIs) is a selective immunosuppressant widely used in organ transplantation. The efficacy and safety of calcineurin inhibitors for the treatment of IgA nephropathy remain uncertain. METHODS: We performed a systematic literature search using the PubMed, Embase, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature (CBM) and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang) for randomized, controlled trials of CNIs therapy of IgA nephropathy...
February 13, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28190517/calcium-mobilizing-treatment-acts-as-a-co-signal-for-tlr-mediated-induction-of-interleukin-12-il-12p70-secretion-by-murine-bone-marrow-derived-dendritic-cells
#9
Emily Huang, Loral Showalter, Shuwen Xu, Brian J Czernliecki, Gary K Koski
We sought to determine whether pharmacological calcium-mobilizing agents could act in cooperation with Toll-like receptor (TLR) signals to induce high-level IL-12 production from murine bone marrow-derived dendritic cells. We found that calcium mobilization alone induced no IL-12, yet dramatically enhanced IL-12p70 secretion elicited by TLR ligands. Enhanced IL-12 production induced by calcium ionophore plus single TLR ligands, but not through dual TLR ligands, was inhibited by the calcineurin antagonist cyclosporine A, suggesting divergent mechanisms of IL-12 induction...
February 1, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28190474/salvianolic-acid-a-inhibits-calpain-activation-and-enos-uncoupling-during-focal-cerebral-ischemia-in-mice
#10
Qaisar Mahmood, Guang-Fa Wang, Gang Wu, Huan Wang, Chang-Xin Zhou, Hong-Yu Yang, Zhi-Rong Liu, Feng Han, Kui Zhao
BACKGROUND: Salvianolic acid A (SAA) is obtained from Chinese herb Salviae Miltiorrhizae Bunge (Labiatae), has been reported to have the protective effects against cardiovascular and neurovascular diseases. HYPOTHESIS: The aim of present study was to investigate the relationship between the effectiveness of SAA against neurovascular injury and its effects on calpain activation and endothelial nitric oxide synthase (eNOS) uncoupling. STUDY DESIGN: SAA or vehicle was given to C57BL/6 male mice for seven days before the occlusion of middle cerebral artery (MCAO) for 60min...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28190435/neurologic-complications-of-transplantation
#11
R Dhar
Major neurologic morbidity, such as seizures and encephalopathy, complicates 20-30% of organ and stem cell transplantation procedures. The majority of these disorders occur in the early posttransplant period, but recipients remain at risk for opportunistic infections and other nervous system disorders for many years. These long-term risks may be increasing as acute survival increases, and a greater number of "sicker" patients are exposed to long-term immunosuppression. Drug neurotoxicity accounts for a significant proportion of complications, with posterior reversible leukoencephalopathy syndrome, primarily associated with calcineurin inhibitors (i...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28188265/the-kinase-cipk23-inhibits-ammonium-transport-in-arabidopsis-thaliana
#12
Tatsiana Straub, Uwe Ludewig, Benjamin Neuhaeuser
Ion transport in plants is not only strictly regulated on a transcriptional level, but it is also regulated posttranslationally. Enzyme modifications such as phosphorylation provide rapid regulation of many plant ion transporters and channels. Upon exposure to high ammonium concentrations in the rhizosphere, the high-affinity AMmonium Transporters (AMT) in Arabidopsis thaliana are efficiently inactivated by phosphorylation to avoid toxic accumulation of cytoplasmic ammonium. External ammonium stimulates the phosphorylation of a conserved threonine in the cytosolic AMT1 C-terminus, which allosterically inactivates AMT1 trimers...
February 10, 2017: Plant Cell
https://www.readbyqxmd.com/read/28186642/higher-calcineurin-inhibitor-levels-predict-better-kidney-graft-survival-in-patients-with-de-novo-donor-specific-anti-hla-antibodies-a-cohort-study
#13
Marc-Antoine Béland, Isabelle Lapointe, Réal Noël, Isabelle Côté, Eric Wagner, Julie Riopel, Eva Latulippe, Olivier Désy, Stéphanie Béland, Ciara N Magee, Isabelle Houde, Sacha A De Serres
The development of de novo anti-HLA donor specific antibodies (dnDSA) is associated with poorer outcomes in kidney transplant recipients. Despite this, antibody screening post-transplant is not widespread, largely because the optimal management of patients with dnDSA remains undetermined. We hypothesized that in this population, calcineurin inhibitor blood levels would be an independent predictor of graft loss. We analyzed a cohort of unsensitized patients for whom anti-HLA antibody screening was performed prospectively post-transplant...
February 10, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28185318/cognitive-function-after-heart-transplantation-comparing-everolimus-based-and-calcineurin-inhibitor-based-regimens
#14
Britta S Bürker, Lars Gullestad, Einar Gude, Anne R Authen, Ingelin Grov, Per K Hol, Arne K Andreassen, Satish Arora, Mary Amanda Dew, Arnt E Fiane, Ira R H Haraldsen, Ulrik F Malt, Stein Andersson
BACKGROUND: Studies have shown conflicting results concerning the occurrence of cognitive impairment after successful heart transplantation (HTx). Another unresolved issue is the possible differential impact of immunosuppressants on cognitive function. In this study, we describe cognitive function in a cohort of HTx recipients and subsequently compare cognitive function between subjects on either everolimus- or calcineurin inhibitor (CNI)-based immunosuppression. METHODS: Cognitive function, covering attention, processing speed, executive functions, memory, and language functions, was assessed with a neuropsychological test battery...
February 10, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28183532/growth-factor-midkine-promotes-nuclear-factor-of-activated-t-cells-regulated-t-cell-activation-and-th1-cell-differentiation-in-lupus-nephritis
#15
Tomohiro Masuda, Kayaho Maeda, Waichi Sato, Tomoki Kosugi, Yuka Sato, Hiroshi Kojima, Noritoshi Kato, Takuji Ishimoto, Naotake Tsuboi, Kenji Uchimura, Yukio Yuzawa, Shoichi Maruyama, Kenji Kadomatsu
Activated T cells play crucial roles in the pathogenesis of autoimmune diseases, including lupus nephritis (LN). The activation of calcineurin/nuclear factor of activated T cells (NFAT) and STAT4 signaling is essential for T cells to perform various effector functions. Here, we identified the growth factor midkine (MK; gene name, Mdk) as a novel regulator in the pathogenesis of 2,6,10,14-tetramethylpentadecane-induced LN via activation of NFAT and IL-12/STAT4 signaling. Wild-type (Mdk(+/+)) mice showed more severe glomerular injury than MK-deficient (Mdk(-/-)) mice, as demonstrated by mesangial hypercellularity and matrix expansion, and glomerular capillary loops with immune-complex deposition...
February 7, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28183531/cardiomyocyte-hypertrophy-in-arrhythmogenic-cardiomyopathy
#16
Mustafa Gerçek, Muhammed Gerçek, Sebastian Kant, Sakine Simsekyilmaz, Astrid Kassner, Hendrik Milting, Elisa A Liehn, Rudolf E Leube, Claudia A Krusche
Arrhythmogenic cardiomyopathy (AC) is a hereditary disease leading to sudden cardiac death or heart failure. AC pathology is characterized by cardiomyocyte loss and replacement fibrosis. Our goal was to determine whether cardiomyocytes respond to AC progression by pathological hypertrophy. To this end, we examined tissue samples from AC patients with end-stage heart failure and tissue samples that were collected at different disease stages from desmoglein 2-mutant mice, a well characterized AC model. We find that cardiomyocyte diameters are significantly increased in right ventricles of AC patients...
February 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28182044/efficacy-and-safety-of-early-tacrolimus-conversion-to-sirolimus-after-kidney-transplantation-long-term-results-of-a-prospective-randomized-study
#17
A E El-Agroudy, S M Alarrayed, S M Al-Ghareeb, E Farid, H Alhelow, S Abdulla
We report a prospective, open-label, randomized study to evaluate the safety and efficacy of converting patients with a stable renal function from tacrolimus (Tac)-based regimen to a sirolimus (SRL)-based regimen after kidney transplantation. Fifty-eight low-risk renal allograft recipients who receiving Tac 6 months posttransplant, were randomly assigned to continue Tac (n = 29) or convert to SRL (n = 29). We evaluated the 3-year outcomes including patient and graft survival, graft function, and safety profile...
January 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28174287/calcineurin-for-t-cell-adhesion
#18
John F Foley
The phosphatase calcineurin not only activates transcription factors but also promotes T cell adhesion upon T cell activation.
February 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/28174168/cardiac-overexpression-of-s100a6-attenuates-cardiomyocyte-apoptosis-and-reduces-infarct-size-after-myocardial-ischemia-reperfusion
#19
Azadeh Mofid, Nadav S Newman, Paul J H Lee, Cynthia Abbasi, Pratiek N Matkar, Dmitriy Rudenko, Michael A Kuliszewski, Hao H Chen, Kolsoom Afrasiabi, James N Tsoporis, Anthony O Gramolini, Kim A Connelly, Thomas G Parker, Howard Leong-Poi
BACKGROUND: Cardiomyocyte-specific transgenic mice overexpressing S100A6, a member of the family of EF-hand calcium-binding proteins, develop less cardiac hypertrophy, interstitial fibrosis, and myocyte apoptosis after permanent coronary ligation, findings that support S100A6 as a potential therapeutic target after acute myocardial infarction. Our purpose was to investigate S100A6 gene therapy for acute myocardial ischemia-reperfusion. METHODS AND RESULTS: We first performed in vitro studies to examine the effects of S100A6 overexpression and knockdown in rat neonatal cardiomyocytes...
February 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28172494/p454-can-calcineurin-inhibitors-induce-a-durable-remission-that-is-maintained-with-vedolizumab-in-ibd
#20
O Kassim, D Micic, B Christensen, J Pekow, A Sakuraba, S Dalal, D Rubin, R Cohen
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
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