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Calcineurin

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https://www.readbyqxmd.com/read/28079600/acute-administration-of-cyclosporine-a-does-not-impair-attention-or-memory-performance-in-healthy-men
#1
Anna L Kahl, Julia Kirchhof, Anna Füting, Bernd-Otto Hütter, Benjamin Wilde, Oliver Witzke, Sven Benson, Martin Hadamitzky, Manfred Schedlowski
There is clinical and experimental evidence that treatment with immunosuppressive and antiproliferative drugs such as the calcineurin inhibitor cyclosporine A (CsA) is associated with mental health problems and neuropsychological disturbances in patients. However, it remains unclear whether and to what extent cognitive functions such as memory and attention processes are affected by the pharmacological treatment. This is partly because of the fact that it is difficult to refer the observed neuropsychological disturbances in patients to the drug itself, to drug-induced immune suppression, or to interaction with other medication or comorbidities...
January 11, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28078646/mucosal-healing-in-ulcerative-colitis-a-comprehensive-review
#2
REVIEW
Pedro Boal Carvalho, José Cotter
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28077617/calcineurin-the-ca2-dependent-phosphatase-regulates-rga2-a-cdc42-gtpase-activating-protein-to-modulate-pheromone-signaling
#3
Nina Ly, Martha S Cyert
Calcineurin, the conserved Ca(2+)/calmodulin-activated phosphatase, is required for viability during prolonged exposure to pheromone, and acts through multiple substrates to down regulate yeast pheromone signaling. Calcineurin regulates Dig2 and Rod1/Art4 to inhibit mating-induced gene expression and activate receptor internalization, respectively. Recent systematic approaches identified Rga2, a GTPase activating protein (GAP) for the Cdc42 Rho-type GTPase, as a calcineurin substrate. Here, we establish a physiological context for this regulation, and show that calcineurin dephosphorylates and positively regulates Rga2 during pheromone signaling...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28077320/serine-threonine-phosphatases-in-atrial-fibrillation
#4
Jordi Heijman, Shokoufeh Ghezelbash, Xander H T Wehrens, Dobromir Dobrev
Serine/threonine protein phosphatases control dephosphorylation of numerous cardiac proteins, including a variety of ion channels and calcium-handling proteins, thereby providing precise post-translational regulation of cardiac electrophysiology and function. Accordingly, dysfunction of this regulation can contribute to the initiation, maintenance and progression of cardiac arrhythmias. Atrial fibrillation (AF) is the most common heart rhythm disorder and is characterized by electrical, autonomic, calcium-handling, contractile, and structural remodeling, which include, among other things, changes in the phosphorylation status of a wide range of proteins...
January 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28073178/polyclonal-and-monoclonal-antibodies-for-induction-therapy-in-kidney-transplant-recipients
#5
REVIEW
Penny Hill, Nicholas B Cross, A Nicholas R Barnett, Suetonia C Palmer, Angela C Webster
BACKGROUND: Prolonging kidney transplant survival is an important clinical priority. Induction immunosuppression with antibody therapy is recommended at transplantation and non-depleting interleukin-2 receptor monoclonal antibodies (IL2Ra) are considered first line. It is suggested that recipients at high risk of rejection should receive lymphocyte-depleting antibodies but the relative benefits and harms of the available agents are uncertain. OBJECTIVES: We aimed to: evaluate the relative and absolute effects of different antibody preparations (except IL2Ra) when used as induction therapy in kidney transplant recipients; determine how the benefits and adverse events vary for each antibody preparation; determine how the benefits and harms vary for different formulations of antibody preparation; and determine whether the benefits and harms vary in specific subgroups of recipients (e...
January 11, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28069324/differences-in-therapeutic-effects-of-topically-applied-corticosteroid-and-tacrolimus-on-atopic-dermatitis-like-symptoms-in-nc-nga-mice
#6
Atsushi Noguchi, Mitsutoshi Tominaga, Nobuaki Takahashi, Hironori Matsuda, Yayoi Kamata, Yoshie Umehara, Kyi Chan Ko, Yasushi Suga, Hideoki Ogawa, Kenji Takamori
BACKGROUND: Topical corticosteroid and calcineurin inhibitor have similar therapeutic benefits in atopic dermatitis (AD), but the differences in therapeutic mechanisms of action of these agents against AD symptoms are not fully understood. OBJECTIVE: This study was performed to examine the different effects of topical betamethasone valerate (BMV), clobetasol propionate (CBP), and tacrolimus (TAC) on itch-related behavior and dermatitis in NC/Nga mice with AD-like symptoms...
December 24, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28063945/calcineurin-inhibitors-improve-memory-loss-and-neuropathological-changes-in-mouse-model-of-dementia
#7
Amit Kumar, Nirmal Singh
AIM: The present study was designed to investigate the potential of Cyclosporine (CsA) and Tacrolimus, the inhibitors of calcineurin (CaN) in cognitive deficits of mice. METHODS: Streptozotocin [STZ, 3mg/kg, injected intracerebroventricular (i.c.v.)] was used to induce memory deficits in NIH mice, while aged mice separately taken served as a natural model of dementia. Morris water maze (MWM) test was employed to evaluate learning and memory of the animals. A battery of biochemical and histopathological studies was also performed...
January 4, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28062573/deficiency-of-n-myristoylation-reveals-calcineurin-activity-as-regulator-of-ifn-%C3%AE-producing-%C3%AE-%C3%AE-t-cells
#8
Francesca Rampoldi, Fabian Brunk, Mahnaz Bonrouhi, Giuseppina Federico, Damir Krunic, Stefan Porubsky, Hermann-Josef Gröne, Zoran V Popovic
γδ T cell subsets can be characterized, in part, by their secretion of select proinflammatory cytokines. The molecular mechanisms driving the diverse fates of γδ T cells have not been elucidated. We have previously shown that the attachment of myristic acid to the N-terminal glycine of proteins, termed N-myristoylation, is essential for αβ T cell development and activation. Here, we explore the potential role of this lipid modification on the activation of γδ T cells. In the absence of N-myristoylation, the CD27(+) γδ T cell subset was dominantly affected...
January 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28061453/the-regulator-of-calcineurin-1-rcan1-inhibits-nuclear-factor-kappab-signaling-pathway-and-suppresses-human-malignant-glioma-cells-growth
#9
Xin Chen, Yuanyuan Hu, Shuo Wang, Xiulian Sun
Nuclear factor-kappaB (NF-κB) has a vital role in cell survival and inhibition of NF-κB had proven to be an efficient therapeutic pathway for various cancers though little is known about the underlying mechanism. Previously we identified regulator of calcineurin 1 (RCAN1) as an endogenous inhibitor of NF-κB signaling pathway in lymphoma. In the present study, we have solid data to show that RCAN1 can inhibit the nuclear translocation of NF-κB protein then affect the activity of NF-κB signaling pathway in glioma cells...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058228/corticosteroid-minimization-in-renal-transplantation-careful-patient-selection-enables-feasibility
#10
Georgios Vlachopanos, Julie M Bridson, Ajay Sharma, Ahmed Halawa
AIM: To explore the benefits and harms of corticosteroid (CS) minimization following renal transplantation. METHODS: CS minimization attempts to improve cardiovascular risk factors (hypertension, diabetes, dyslipidemia), to enhance growth in children, to ameliorate bone disease and to lead to better compliance with immunosuppressive agents. Nevertheless, any benefit must be carefully weighed against the reduction in net immunosuppression and the potential harm to renal allograft function and survival...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28058220/tacrolimus-confers-lower-acute-rejection-rates-and-better-renal-allograft-survival-compared-to-cyclosporine
#11
Mahmoud Kamel, Manish Kadian, Titte Srinivas, David Taber, Maria Aurora Posadas Salas
AIM: To compare the impact of tacrolimus (FK) and cyclosporine (CYA) on acute rejection and graft survival and to assess the predominant causes of graft loss between patients receiving these two calcineurin inhibitors (CNIs). METHODS: Retrospective review of 1835 patients who received a kidney transplant (KTX) between 1999-2012. Patients were grouped based on initial CNI utilized: 1195 in FK group, 640 in CYA group. Data on baseline characteristics, clinical outcomes, and causes of graft loss in both groups were analyzed...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28055124/interventions-for-the-management-of-oral-lichen-planus-a-review-of-the-conventional-and-novel-therapies
#12
REVIEW
Shikha Gupta, Sujoy Ghosh, Sunita Gupta
OBJECTIVE: This narrative review focuses on the rationale & role of conventional and newer therapies in the management of Oral lichen planus with emphasis on randomized controlled trials reported over 2 decades. MATERIALS AND METHODS: Literature search was conducted to identify randomized controlled trials for management of OLP from 1/1/1995 to 31/12/2015; Medline, and Cochrane databases complemented with manual search was used. Primary outcome as resolution of pain was evaluated with analysis of clinical resolution of erythema and ulceration as secondary outcome...
January 5, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28052276/short-and-long-term-outcomes-of-infliximab-treatment-for-steroid-refractory-ulcerative-colitis-and-related-prognostic-factors-a-single-center-retrospective-study
#13
Masanao Nasuno, Maki Miyakawa, Hiroki Tanaka, Satoshi Motoya
BACKGROUND/AIMS: The aim of this study was to analyze the short- and long-term outcomes of infliximab (IFX) treatment to cure steroid-refractory ulcerative colitis (UC) and related prognostic factors. METHODS: Retrospective data were collected from 125 patients with steroid-refractory UC who received IFX treatment at our center from July 2005 to November 2013. The Lichtiger clinical activity index score was calculated at baseline, 2 weeks, 6 weeks, and 1 year, and the cumulative non-colectomy rate following IFX administration was estimated...
2017: Digestion
https://www.readbyqxmd.com/read/28051798/%C3%A2-conversion-to-mycophenolate-mofetil-monotherapy-in-liver-recipients-calcineurin-inhibitor-levels-are-key
#14
Blanca Norero, Carolina A Serrano, Alberto Sanchez-Fueyo, Ignacio Duarte, Javiera Torres, Mauricio Ocquetau, Francisco Barrera, Marco Arrese, Alejandro Soza, Carlos Benítez
 The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28050266/from-slow-to-fast-hypogravity-induced-remodeling-of-muscle-fiber-myosin-phenotype
#15
B S Shenkman
Skeletal muscle consists of different fiber types arranged in a mosaic pattern. These fiber types are characterized by specific functional properties. Slow-type fibers demonstrate a high level of fatigue resistance and prolonged contraction duration, but decreased maximum contraction force and velocity. Fast-type fibers demonstrate high contraction force and velocity, but profound fatigability. During the last decades, it has been discovered that all these properties are determined by the predominance of slow or fast myosin-heavy-chain (MyHC) isoforms...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28049841/trail-death-receptor-endocytosis-and-apoptosis-are-selectively-regulated-by-dynamin-1-activation
#16
Carlos R Reis, Ping-Hung Chen, Nawal Bendris, Sandra L Schmid
Clathrin-mediated endocytosis (CME) constitutes the major pathway for uptake of signaling receptors into eukaryotic cells. As such, CME regulates signaling from cell-surface receptors, but whether and how specific signaling receptors reciprocally regulate the CME machinery remains an open question. Although best studied for its role in membrane fission, the GTPase dynamin also regulates early stages of CME. We recently reported that dynamin-1 (Dyn1), previously assumed to be neuron-specific, can be selectively activated in cancer cells to alter endocytic trafficking...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28042353/immunosuppressive-therapy-after-solid-organ-transplantation-does-the-intermed-identify-patients-at-risk-of-poor-adherence
#17
Laurent Michaud, Gundula Ludwig, Sylvie Berney, Stéphanie Rodrigues, Anne Niquille, Valérie Santschi, Anne-Sophie Favre, Anne-Catherine Lange, Annemieke A Michels, Bernard Vrijens, Olivier Bugnon, Nathalie Pilon, Manuel Pascual, Jean-Pierre Venetz, Friedrich Stiefel, Marie-Paule Schneider
BACKGROUND: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT) recipients. OBJECTIVE: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20) might have lower medication adherence than noncomplex patients (INTERMED≤20)...
October 2016: Pharmacy Practice
https://www.readbyqxmd.com/read/28041666/prediabetes-in-pediatric-recipients-of-liver-transplant-mechanism-and-risk-factors
#18
Emily R Perito, Robert H Lustig, Philip Rosenthal
OBJECTIVE: To investigate the role of calcineurin inhibitor exposure and states of insulin resistance-obesity and adolescence-in prediabetes after pediatric liver transplant via oral glucose tolerance testing, which previously has not been done systematically in these at-risk youths. STUDY DESIGN: This was a cross-sectional study of 81 pediatric recipients of liver transplant. Prediabetes was defined as impaired glucose tolerance (IGT; glucose ≥140 mg/dL at 2 hours) or impaired fasting glucose (IFG, ≥100 mg/dL)...
December 29, 2016: Journal of Pediatrics
https://www.readbyqxmd.com/read/28040832/renal-transplantation-outcomes-following-heart-and-heart-lung-transplantation
#19
L Wong, Y R Chee, D G Healy, J J Egan, D M Sadlier, Y M O'Meara
BACKGROUND: Chronic kidney disease is a frequent complication following heart and combined heart-lung transplantation. The aim of this study was to analyse the outcome of a subsequent renal transplant in heart, lung and heart-lung transplantation recipients. METHODS: All heart, lung and heart-lung transplant recipients who received a subsequent renal transplant over a 27-year period in a national heart and lung transplant centre were included in this study. RESULTS: A total of 18 patients who had previously undergone heart (n = 6), lung (n = 7) and heart-lung (n = 5) transplantation received a renal transplant...
December 31, 2016: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28035723/tacrolimus-improves-proteinuria-remission-in-adults-with-cyclosporine-a-resistant-or-dependent-minimal-change-disease
#20
Dechao Xu, Xiang Gao, Rongrong Bian, Changlin Mei, Chenggang Xu
AIMS: Cyclosporin A (CsA) is considered as an effective treatment option for steroid-resistant or-dependent patients with adult-onset minimal change disease (MCD). However, CsA resistance or dependence is also observed in these patients. Tacrolimus (TAC) is a calcineurin inhibitor that is potent in cytokine suppression. The authors aim to evaluate the efficacy and safety of TAC therapy in CsA-resistant and-dependent adult-onset MCD patients. METHODS: Patients with adult-onset MCD were enrolled in our department from 2008 to 2012...
December 30, 2016: Nephrology
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