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Calcineurin

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https://www.readbyqxmd.com/read/28318625/mycophenolate-mofetil-is-inferior-to-tacrolimus-in-sustaining-remission-in-children-with-idiopathic-steroid-resistant-nephrotic-syndrome
#1
Aditi Sinha, Aarti Gupta, Mani Kalaivani, Pankaj Hari, Amit K Dinda, Arvind Bagga
Studies of nephrotic syndrome show that substitution of calcineurin inhibitors by mycophenolate mofetil (MMF) enables sustained remission and corticosteroid sparing and avoids therapy associated adverse effects. However, controlled studies in patients with steroid resistance are lacking. Here we examined the effect of switching from therapy with tacrolimus to MMF on disease course in an open-label, one-to-one randomized, controlled trial on children (one to 18 years old), recently diagnosed with steroid-resistant nephrotic syndrome, at a referral center in India...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28315818/sclerosing-encapsulated-peritonitis-a-devastating-and-infrequent-disease-complicating-kidney-transplantation-case-report-and-literature-review
#2
Liliana Caicedo, Alejandro Delgado, Luis A Caicedo, Juan Carlos Bravo, Laura S Thomas, Martin Rengifo, Jorge I Villegas, Oscar Serrano, Gabriel J Echeverri
INTRODUCTION: Sclerosing Encapsulating Peritonitis (SEP) is a rare condition with an incidence of up to 3% and a mortality of up to 51% among peritoneal dialysis (PD) patients (Brown et al., Korte et al. and Kawanishi et al.). In the last ten years, the incidence of SEP in kidney transplant recipients has increased (Nakamoto, de Sousa et al. and Korte et al.). PRESENTATION OF CASE: A 31-year old male with a 15 years history of PD and later kidney retransplantation was admitted to the emergency service after experiencing several weeks of diffuse abdominal pain which had escalated to include vomiting and diarrhea during the 24h previous to admission...
March 1, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28314744/randomised-controlled-trial-comparing-ofatumumab-to-rituximab-in-children-with-steroid-dependent-and-calcineurin-inhibitor-dependent-idiopathic-nephrotic-syndrome-study-protocol
#3
Pietro Ravani, Alice Bonanni, Gian Marco Ghiggeri
INTRODUCTION: Oral steroids induce remission in about 90% of children with idiopathic nephrotic syndrome (INS), which is characterised by severe proteinuria and hypoalbuminaemia. Some children become steroid-dependent (SD) and require addition of calcineurin inhibitors (CNI) to maintain remission. Since these oral agents are toxic, alternative interventions are needed for long-term treatment. The anti-CD20 antibody rituximab has shown promising steroid-sparing properties in clinical trials, but benefits are less convincing in complicated forms of SD-INS...
March 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28303389/variability-of-diagnostic-criteria-and-treatment-of-idiopathic-nephrotic-syndrome-across-european-countries
#4
Georges Deschênes, Marina Vivarelli, Licia Peruzzi
The aim of the surveys conducted by the Idiopathic Nephrotic Syndrome Working Group of the ESPN was to study the possible variability of treatment in Europe at different stages of the disease by means of questionnaires sent to members of the Working Group. Four surveys have been completed: treatment of the first flare, treatment of the first relapse and the issue of steroid dependency, use of rituximab, and the management of steroid-resistant patients. A uniform treatment of the first flare was applied in only three countries, and ten additional centers have adopted one of the three main protocols...
March 16, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28302995/conversion-from-calcineurin-inhibitor-based-immunosuppression-to-mycophenolate-mofetil-in-monotherapy-reduces-risk-of-de-novo-malignancies-after-liver-transplantation
#5
Diego Aguiar, Diego Martínez-Urbistondo, Delia D'Avola, Mercedes Iñarrairaegui, Fernando Pardo, Fernando Rotellar, Bruno Sangro, Jorge Quiroga, Jose Ignacio Herrero
BACKGROUND Immunosuppression increases the risk of malignancy in liver transplant recipients. The potential impact of mycophenolate mofetil monotherapy on this risk has not been studied. MATERIAL AND METHODS The incidence and risk factors for de novo malignancies of 392 liver transplant recipients with a survival higher than 3 months and a mean follow-up of 8.5 years were studied. RESULTS De novo malignancies were diagnosed in 126 patients (32.1%) (64 non-melanoma skin cancer and 81 other malignancies). Sixty-nine patients (18...
March 17, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28301626/zoon-balanitis-revisited-report-of-balanitis-circumscripta-plasmacellularis-resolving-with-topical-mupirocin-ointment-monotherapy
#6
Michael A Lee, Philip R Cohen
<p>INTRODUCTION: Zoon balanitis is an idiopathic benign inflammatory condition of the glans penis and prepuce. A patient with biopsy confirmed diagnosis of Zoon balanitis who was successfully treated with topical mupirocin ointment monotherapy is described.</p> <p>METHOD: A search using PubMed database was performed using the following terms: Zoon balanitis (cases, diagnosis, treatment of), balanitis circumscripta plasmacellularis, and mupirocin. Relevant papers and their reference citations were reviewed and evaluated...
March 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28301621/treatment-of-atopic-dermatitis-in-the-united-states-analysis-of-data-from-the-national-ambulatory-medical-care-survey
#7
Sean P McGregor, Michael E Farhangian, Karen E Huang, Steven R Feldman
<p>Introduction: Atopic dermatitis (AD) affects both adult and pediatric patients, and multiple practitioners encounter and manage AD. However, differences with regard to the treatment of AD between specialties are not well characterized. OBJECTIVE: The primary objective of this study was to determine if there is a difference between dermatologists and non-dermatology specialties with regard to treatment strategies for AD and to describe those differences. METHODS: Data from the 1993-2010 National Ambulatory Medical Care (NAMCS) and National Hospital Ambulatory Care (NHAMCS) Surveys were used to characterize outpatient visits made for AD...
March 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28300440/review-of-atopic-dermatitis-and-topical-therapies
#8
Julia N Mayba, Melinda J Gooderham
Atopic dermatitis is one of the most common skin disorders in the developed world, affecting up to 20% of children and 1% to 3% of adults. This review concisely explains the pathophysiology and epidemiology of atopic dermatitis, as well as potential challenges facing its successful treatment. Furthermore, mainstay topical treatment modalities are evaluated, such as emollients, topical corticosteroids, and topical calcineurin inhibitors. The use of topical corticosteroids and topical calcineurin inhibitors in combination is discussed, as studies have indicated encouraging results...
December 1, 2016: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28299629/inhibition-of-calcineurin-a-by-fk506-suppresses-seizures-and-reduces-the-expression-of-glun2b-in-membrane-fraction
#9
Yuetao Wen, Pengfei Fu, Kunlun Wu, Kaichuang Si, Yanfeng Xie, Wei Dan, Yan Zhan, Quanhong Shi
FK506, a calcineurin inhibitor, shows neuroprotective effects and has been associated with neurodegenerative diseases. Calcineurin A (CaNA), a catalytic subunit of calcineurin, mediates the dephosphorylation of various proteins. N-methyl-D-aspartate receptor (GluN) is closely related to epileptogenesis, and various phosphorylation sites of GluN2B, a regulatory subunit of the GluN complex, have different functions. Thus, we hypothesized that one of the potential anti-epileptic mechanisms of FK506 is mediated by its ability to promote the phosphorylation of GluN2B and reduce the expression of GluN2B in membrane fraction by down-regulating CaNA...
March 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28296184/long-term-administration-of-pyridostigmine-attenuates-pressure-overload-induced-cardiac-hypertrophy-by-inhibiting-calcineurin-signalling
#10
Yi Lu, Ming Zhao, Jin-Jun Liu, Xi He, Xiao-Jiang Yu, Long-Zhu Liu, Lei Sun, Li-Na Chen, Wei-Jin Zang
Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms...
March 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28292468/microrna-34a-targets-regulator-of-calcineurin-1-to-modulate-endothelial-inflammation-after-fetal-cardiac-bypass-in-goat-placenta
#11
Hai-Yun Yuan, Cheng-Bin Zhou, Ji-Mei Chen, Xiao-Bing Liu, Shu-Sheng Wen, Gang Xu, Jian Zhuang
INTRODUCTION: Placental dysfunction characterized by vascular endothelial inflammation is one of the most notable responses to fetal cardiac bypass. Regulator of calcineurin 1 (RCAN1) is an important regulator of inflammatory responses. MicroRNAs (miRNAs) are essential post-transcriptional modulators of gene expression, and miRNA-34a (miR-34a) was showed to activate vascular endothelial inflammation. We hypothesized that miR-34a may be a key regulator of placental dysfunction after fetal cardiac bypass...
March 2017: Placenta
https://www.readbyqxmd.com/read/28292384/association-of-learning-and-memory-calcineurin-binding-protein-with-autism-spectrum-disorders
#12
(no author information available yet)
OBJECTIVE: To determine the association of learning and memory calcineurin binding (CABIN1) protein with autism spectrum disorders. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: The Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Saudi Arabia, from October 2013 to May 2014. METHODOLOGY: Serum levels of CABIN1 protein in 62 (64%) autistic male children were analysed and 35 (36%) age healthy children measured by using ELISA...
February 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28289712/rcan1-4-is-a-thyroid-cancer-growth-and-metastasis-suppressor
#13
Chaojie Wang, Motoyasu Saji, Steven E Justiniano, Adlina Mohd Yusof, Xiaoli Zhang, Lianbo Yu, Soledad Fernández, Paul Wakely, Krista La Perle, Hiroshi Nakanishi, Neal Pohlman, Matthew D Ringel
Metastasis suppressors are key regulators of tumor growth, invasion, and metastases. Loss of metastasis suppressors has been associated with aggressive tumor behaviors and metastatic progression. We previously showed that regulator of calcineurin 1, isoform 4 (RCAN1-4) was upregulated by the KiSS1 metastatic suppression pathway and could inhibit cell motility when overexpressed in cancer cells. To test the effects of endogenous RCAN1-4 loss on thyroid cancer in vivo, we developed RCAN1-4 knockdown stable cells...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28289708/interruption-of-ox40l-signaling-prevents-costimulation-blockade-resistant-allograft-rejection
#14
William H Kitchens, Ying Dong, David V Mathews, Cynthia P Breeden, Elizabeth Strobert, Maria E Fuentes, Christian P Larsen, Mandy L Ford, Andrew B Adams
The potential of costimulation blockade to serve as a novel transplant immunosuppression strategy has been explored for over 20 years, culminating in the recent clinical approval of belatacept for renal transplant patients. Despite improving long-term graft function and survival compared with calcineurin inhibitors, clinical acceptance of belatacept has been hindered by elevated rates of acute rejection. We examined the signaling pathways required to activate costimulation blockade-resistant alloreactive T cells and identified the OX40/OX40L secondary costimulatory pathway as a promising target...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288505/the-use-of-immunosuppression-in-autoimmune-hepatitis-a-current-literature-review
#15
Angela Cropley, Martin Weltman
Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent...
March 14, 2017: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28287636/transplant-associated-thrombotic-microangiopathy-opening-pandora-s-box
#16
REVIEW
E Gavriilaki, I Sakellari, A Anagnostopoulos, R A Brodsky
Transplant-associated thrombotic microangiopathy (TA-TMA) is an early complication of hematopoietic cell transplantation (HCT). A high mortality rate is documented in patients who are refractory to calcineurin inhibitor cessation. Estimates of TA-TMA prevalence vary significantly and are higher in allogeneic compared with autologous HCT. Furthermore, our understanding of the pathophysiology that is strongly related to diagnosis and treatment options is limited. Recent evidence has linked TA-TMA with atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative pathway of complement, opening the Pandora's box in treatment options...
March 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28286787/topical-tacrolimus-in-anterior-segment-inflammatory-disorders
#17
REVIEW
Samir S Shoughy
Immune mediated inflammatory anterior segment diseases are variable and their management requires intense immunosuppression. Treatment with topical steroids is associated with serious ocular side effects. In order to overcome the potentially blinding complications of topical steroids, immunomodulatory drugs are being used more frequently. Tacrolimus is a calcineurin inhibitor that induces suppression of T lymphocytes activity and reduction of ocular inflammation. Tacrolimus was recently investigated for application in various anterior segment inflammatory disorders...
2017: Eye and Vision (London, England)
https://www.readbyqxmd.com/read/28280692/influence-of-tacrolimus-metabolism-rate-on-renal-function-after-solid-organ-transplantation
#18
REVIEW
Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter
The calcineurin inhibitor (CNI) tacrolimus (TAC) is an integral part of the immunosuppressive regimen after solid organ transplantation. Although TAC is very effective in prevention of acute rejection episodes, its highly variable pharmacokinetic and narrow therapeutic window require frequent monitoring of drug levels and dose adjustments. TAC can cause CNI nephrotoxicity even at low blood trough levels (4-6 ng/mL). Thus, other factors besides the TAC trough level might contribute to CNI-related kidney injury...
February 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28279567/optimizing-everolimus-exposure-when-combined-with-calcineurin-inhibitors-in-solid-organ-transplantation
#19
REVIEW
Teun van Gelder, Lutz Fischer, Fuad Shihab, Maria Shipkova
The mammalian target of rapamycin (mTOR) inhibitor everolimus is a narrow therapeutic index drug for which optimal exposure levels are essential. The consistent pharmacokinetic profile of everolimus allows trough concentration (C0) measurement to be an appropriate and reliable index for therapeutic drug monitoring (TDM). Exposure-response analyses of data from early fixed-dose trials demonstrated that rates of biopsy-proven acute rejection (BPAR) are significantly higher if everolimus C0 declines below 3 ng/mL, an observation confirmed in subsequent concentration-controlled trials...
February 27, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28278204/sarcolipin-deletion-exacerbates-soleus-muscle-atrophy-and-weakness-in-phospholamban-overexpressing-mice
#20
Val A Fajardo, Daniel Gamu, Andrew Mitchell, Darin Bloemberg, Eric Bombardier, Paige J Chambers, Catherine Bellissimo, Joe Quadrilatero, A Russell Tupling
Sarcolipin (SLN) and phospholamban (PLN) are two small proteins that regulate the sarco(endo)plasmic reticulum Ca2+-ATPase pumps. In a recent study, we discovered that Pln overexpression (PlnOE) in slow-twitch type I skeletal muscle fibers drastically impaired SERCA function and caused a centronuclear myopathy-like phenotype, severe muscle atrophy and weakness, and an 8 to 9-fold upregulation of SLN protein in the soleus muscles. Here, we sought to determine the physiological role of SLN upregulation, and based on its role as a SERCA inhibitor, we hypothesized that it would represent a maladaptive response that contributes to the SERCA dysfunction and the overall myopathy observed in the PlnOE mice...
2017: PloS One
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