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Calcineurin

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https://www.readbyqxmd.com/read/29781948/outcomes-of-pediatric-abo-incompatible-living-kidney-transplantations-from-2002-to-2015-an-analysis-of-the-japanese-kidney-transplant-registry
#1
Motoshi Hattori, Makiko Mieno, Seiichiro Shishido, Atsushi Aikawa, Hidetaka Ushigome, Shinichi Ohshima, Kota Takahashi, Akira Hasegawa
BACKGROUND: Extensive data have been accumulated for adults who have undergone ABO-incompatible (ABOi)-living kidney transplantation (LKT). In contrast, available published data on pediatric recipients who underwent ABOi-LKT from the early to middle 2000s is very limited. Thus, pediatric ABOi-LKT has remained relatively rare and there is a lack of large, multicenter data. METHODS: We analyzed data from the Japanese Kidney Transplant Registry to clarify the patient and graft outcomes of pediatric recipients who underwent ABOi-LKT from 2002 to 2015...
April 30, 2018: Transplantation
https://www.readbyqxmd.com/read/29779413/tailoring-tacrolimus-therapy-in-kidney-transplantation
#2
Thomas Jouve, Johan Noble, Lionel Rostaing, Paolo Malvezzi
BACKGROUND: The prevalence of end-stage renal disease is increasing worldwide. The best treatment is kidney transplantation, although life-long immunosuppressive therapy is then mandatory. Currently, the cornerstone immunosuppressive therapy relies on tacrolimus, a calcineurin inhibitor that is nephrotoxic but whose exposition can be minimized in a delicate balance. Area covered: We addressed whether, in the setting of kidney transplantation, tacrolimus-based therapy can be tailored to medical needs: to achieve this, we searched for suitable articles in PubMed...
May 19, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29777594/il-3-producing-basophils-are-required-to-exacerbate-airway-hyper-responsiveness-in-a-murine-inflammatory-model
#3
Rachel Rignault-Bricard, François Machavoine, Salah Mecheri, Olivier Hermine, Elke Schneider, Michel Dy, Maria Leite-de-Moraes
BACKGROUND: Basophils are commonly associated with allergic responses because of their ability to produce large amounts of pro-Th2 cytokines and histamine. However, the mechanisms through which bone marrow-resident basophils (BMRB) become fully competent cytokine and histamine producers in response to IgE crosslinking are poorly understood. Here, we sought to determine the role of IL-3 in promoting pro-Th2 basophils. METHODS: BMRB and basophils exposed to IL-3 in vitro and in vivo were evaluated for their production of Th2 cytokines and histamine in response to FcεRI crosslinking on both protein and gene expression levels...
May 19, 2018: Allergy
https://www.readbyqxmd.com/read/29777361/tremor-induced-by-calcineurin-inhibitor-immunosuppression-a-single-centre-observational-study-in-kidney-transplanted-patients
#4
R Erro, Ruggero Bacchin, F Magrinelli, P Tomei, C Geroin, G Squintani, A Lupo, G Zaza, M Tinazzi
INTRODUCTION: Tremor is the most frequent and disabling neurological side effect under Calcineurin inhibitor-induced immunosuppression, but no studies have defined its phenomenology, severity, distribution, the impact on quality of life, as well as of other neurological symptoms associated. METHODS: 126 consecutive kidney-transplanted patients, under treatment with Cyclosporin A, Tacrolimus and non-Calcineurin inhibitors, within therapeutic range, were enrolled...
May 18, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29775447/-mycophenolate-mofetil-mmf-as-the-first-choice-immunosuppressive-drug-in-treatment-of-steroid-dependent-nephrotic-syndrome-in-children
#5
Iwona Ogarek, Elżbieta Szczęsny-Choruz, Ewa Wierzchowska-Słowiaczek, Joanna Kwinta-Rybicka, Zofia Stec, Anna Moczulska, Katarzyna Wilkosz, Dorota Drożdż
Most children diagnosed with nephrotic syndrome show favourable response to corticosteroid therapy, nonetheless 30% of patients have frequent relapses or a steroid-dependent course of disease. Cyclophosphamide, cyclosporin A or MMF are being used in treatment of steroid-dependent nephrotic syndrome in search of a drug with highest long-term effectiveness and least amount of side effects. AIM: The aim of study was to assess of the efficacy of MMF as the first choice immunosuppressive drug in children with nephrotic syndrome after determining a steroid-dependency...
April 23, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29773102/-over-expression-of-bdnf-inhibits-angiotensin-ii-induced-apoptosis-of-cardiomyocytes-in-sd-rats
#6
Jingli Cao, Yingfeng Wu, Geming Liu, Zhenlong Li
Objective To investigate the role and molecular mechanism of brain-derived neurotrophic factor (BDNF) against the process of cardiomyocyte hypertrophy and apoptosis. Methods Cardiomyocyte hypertrophy were estabolished by angiotensin II (Ang II) in neonatal cardiomyocytes in vitro and incomplete ligature of abdominal aorta of SD rats in vivo. BDNF over-expressing recombinant vector pcDNA5-BDNF was transfected into cardiomyocytes by liposomes. Immunofluorescence staining was used to detect the effect of BDNF transfection on the surface area of myocardial cells...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29771270/effect-of-conversion-from-calcineurin-inhibitors-to-everolimus-on-hepatitis-c-viremia-in-adult-kidney-transplant-recipients
#7
Larissa Sgaria Pacheco, Valter Duro Garcia, Ronivan Luis Dal Prá, Bruna Doleys Cardoso, Mariana Ferras Rodrigues, Helen Kris Zanetti, Gisele Meinerz, Jorge Neumann, Diego Gnatta, Elizete Keitel
INTRODUCTION: Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. METHOD: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors...
May 14, 2018: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29770600/how-does-glucagon-like-peptide-1-stimulate-human-%C3%AE-cell-proliferation-a-lesson-from-islet-graft-experiments
#8
Yoshio Fujitani
The incidence of type 2 diabetes increases with age. The age-dependent decline in functional β-cell mass contributes to the increased risk of onset of diabetes, reflecting the central role of pancreatic β cells in glucose homeostasis. Indeed, the replication rate of human and rodent β cells is known to decline sharply with age, and such a characteristic of β cells may explain the increased onset of type 2 diabetes in the older population. The molecular mechanism involved in the age-dependent decline of β-cell proliferation has been extensively studied, mainly using rodents and in vitro culture systems, but its molecular basis is still largely unknown...
May 16, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29767755/protein-phosphatase-2c-ap2c1-interacts-with-and-negatively-regulates-the-function-of-cipk9-under-potassium-deficient-conditions-in-arabidopsis
#9
Amarjeet Singh, Akhilesh K Yadav, Kanwaljeet Kaur, Sibaji K Sanyal, Saroj K Jha, Joel L Fernandes, Pankhuri Sharma, Indu Tokas, Amita Pandey, Sheng Luan, Girdhar K Pandey
Potassium (K+) is a major macronutrient required for plant growth. In response to low- K+ condition, an adaptive mechanism entails activation of the Ca2+ signaling network consisting of calcineurin B-like proteins (CBLs) and their interacting kinases (CIPKs) in plants. The CBL-interacting protein kinase 9 (CIPK9) is previously implicated in low-K+ responses in Arabidopsis thaliana. Here, we report a protein phosphatase 2C (PP2C), AP2C1, as an interactor of CIPK9. Fluorescence resonance energy transfer (FRET), bimolecular fluorescence complementation (BiFC) and co-localization analyses revealed that CIPK9 and AP2C1 interact in the cytoplasm...
May 15, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29767445/comparison-of-de-novo-igm-and-igg-anti-hla-dsa-between-belatacept-and-calcineurin-treated-patients-an-analysis-of-the-benefit-and-benefit-ext-trial-cohorts
#10
Matthew J Everly, Mustimbo Roberts, Robert Townsend, Robert A Bray, Howard M Gebel
Preventing conversion of donor-specific anti-HLA antibodies (DSA) from an IgM-to-IgG could a way to prevent chronic rejection. We evaluated whether belatacept-treated patients [belatacept less-intensive (LI) more-intensive (MI) regimens] have a lower rate of conversion than cyclosporine A (CsA) treated patients. We included 330 HLA mismatched patients from two phase-3 trials with either (a) complete donor/recipient HLA-A,-B,-DR, and -DQ loci typing or (b) incomplete HLA typing with IgG DSA detected pre- or post-transplant...
May 16, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29764979/the-complex-relationship-between-tfeb-transcription-factor-phosphorylation-and-subcellular-localization
#11
REVIEW
Rosa Puertollano, Shawn M Ferguson, James Brugarolas, Andrea Ballabio
The MiT-TFE family of basic helix-loop-helix leucine-zipper transcription factors includes four members: TFEB, TFE3, TFEC, and MITF Originally described as oncogenes, these factors play a major role as regulators of lysosome biogenesis, cellular energy homeostasis, and autophagy. An important mechanism by which these transcription factors are regulated involves their shuttling between the surface of lysosomes, the cytoplasm, and the nucleus. Such dynamic changes in subcellular localization occur in response to nutrient fluctuations and various forms of cell stress and are mediated by changes in the phosphorylation of multiple conserved amino acids...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29761378/inhibition-and-substrate-specificity-properties-of-fkbp22-from-a-psychrotrophic-bacterium-shewanella-sp-sib1
#12
Cahyo Budiman, Herman Umbau Lindang, Bo Eng Cheong, Kenneth F Rodrigues
SIB1 FKBP22 is a peptidyl prolyl cis-trans isomerase (PPIase) member from a psychrotrophic bacterium, Shewanella sp. SIB1, consisting of N- and C-domains responsible for dimerization and catalytic PPIase activity, respectively. This protein was assumed to be involved in cold adaptation of SIB1 cells through its dual activity of PPIase activity and chaperone like-function. Nevertheless, the catalytic inhibition by FK506 and its substrate specificity remain unknown. Besides, ability of SIB1 FKBP22 to inhibit phosphatase activity of calcinuerin is also interesting to be studied since it may reflect wider cellular functions of SIB1 FKBP22...
May 14, 2018: Protein Journal
https://www.readbyqxmd.com/read/29760186/hypertrophic-cardiomyopathy-mutations-increase-myofilament-ca-2-buffering-alter-intracellular-ca-2-handling-and-stimulate-ca-2-dependent-signalling
#13
Paul Robinson, Xing Liu, Alexander Sparrow, Suketu Patel, Yin Hua Zhang, Barbara Casadei, Hugh Watkins, Charles S Redwood
Mutations in thin filament regulatory proteins that cause hypertrophic cardiomyopathy (HCM) increase myofilament Ca2+ -sensitivity. Mouse models exhibit increased Ca2+ buffering and arrhythmias, and we hypothesized that these changes are primary effects of the mutations (independent of compensatory changes) and that increased Ca2+ - buffering and altered Ca2+ -handling contribute to HCM pathogenesis via activation of Ca2+ -dependent signalling. Here, we determined the primary effects of HCM mutations on intracellular Ca2+ -handling and Ca2+ -dependent signalling in a model system possessing Ca2+ -handling mechanisms and contractile protein isoforms close to human in the absence of potentially confounding remodeling...
May 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29757894/immunosuppression-is-associated-with-clinical-features-and-relapse-risk-of-b-cell-posttransplant-lymphoproliferative-disorder-a-retrospective-analysis-based-on-the-prospective-international-multicenter-ptld-1-trials
#14
Heiner Zimmermann, Nina Babel, Daan Dierickx, Franck Morschhauser, Peter Mollee, Jan M Zaucha, Martin H Dreyling, Ulrich Dührsen, Petra Reinke, Gregor Verhoef, Marion Subklewe, Andreas Hüttmann, Thomas Tousseyn, Emmanuel Bachy, Ingeborg A Hauser, Corrado Tarella, Eric Van Den Neste, Olivier Gheysens, Ioannis Anagnostopoulos, Veronique Leblond, Hanno Riess, Sylvain Choquet, Ralf U Trappe
BACKGROUND: Current guideline recommendations for immunosuppression reduction after diagnosis of posttransplant lymphoproliferative disorder (PTLD) include stopping antimetabolites, reducing calcineurin inhibitors and maintaining corticosteroids. However, the effect of immunosuppression on PTLD relapse risk after up-to-date therapy is unclear. METHODS: This is a retrospective analysis of immunosuppression, patient baseline characteristics and relapse risk measured as landmark time to progression (TTP) starting 1 year after start of therapy in 159 patients with B cell PTLD after solid organ transplantation treated in the prospective, international, multicenter PTLD-1 trials with either sequential treatment (rituximab followed by CHOP chemotherapy) or risk-stratified sequential treatment (rituximab followed by rituximab or R-CHOP immunochemotherapy)...
May 11, 2018: Transplantation
https://www.readbyqxmd.com/read/29757603/alzheimer-s-disease-dendritic-spines-and-calcineurin-inhibitors-a-new-approach
#15
Melissa A O'Neal, Nancy R Stallings, James S Malter
Therapeutics to effectively treat Alzheimer's disease (AD) are lacking. In vitro, animal and human studies have implicated the excessive activation of the protein phosphatase calcineurin (CN) as an early step in the pathogenesis of AD. We discuss recent data showing that the prolyl isomerase Pin1 is suppressed by CN-mediated dephosphorylation induced by Aβ42 signaling. Pin1 loss directly leads to the reductions in dendritic spines and synapses characteristic of early AD pathology. Pin1 activity, and synapse and dendritic spine numbers are rescued by FK506, a highly specific and United States Food and Drug Administration approved CN inhibitor...
May 14, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29757021/advagraf%C3%A2-with-or-without-an-induction-therapy-for-de-novo-kidney-transplant-recipients
#16
Johan Noble, Thomas Jouve, Lionel Rostaing, Paolo Malvezzi
Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company). Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i...
May 14, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29754746/rs3212227-snp-in-the-il12b-gene-prevents-delayed-graft-function-after-kidney-transplantation
#17
Vladimir Perovic, Milos Markovic, Milica Kravljaca, Emina Milosevic, Milica Djoric, Vera Pravica, Radomir Naumovic
BACKGROUND AND AIMS: Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients...
May 10, 2018: Archives of Medical Research
https://www.readbyqxmd.com/read/29753462/limitation-of-terminal-serum-creatinine-as-a-kidney-donor-profile-index-variable-in-predicting-long-term-kidney-transplant-outcomes
#18
B Chopra, K K Sureshkumar
BACKGROUND: Donor final serum creatinine (SCr) is a dynamic variable and is 1 of 10 factors used in calculating kidney donor profile index (KDPI). We hypothesize that deceased-donor kidneys (DDKs) with higher SCr were likely accepted for transplantation if procurement biopsy findings were favorable and with long-term outcomes no worse than kidneys with lower final SCr within a KDPI group. METHODS: Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified DDK transplant recipients from 2000 to 2015 who received induction and calcineurin inhibitor/mycophenolate mofetil maintenance...
March 12, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29752633/clinical-pharmacokinetic-and-pharmacodynamic-considerations-in-the-treatment-of-ulcerative-colitis
#19
REVIEW
Sophie E Berends, Anne S Strik, Mark Löwenberg, Geert R D'Haens, Ron A A Mathôt
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology, probably caused by a combination of genetic and environmental factors. The treatment of patients with active UC depends on the severity, localization and history of IBD medication. According to the classic step-up approach, treatment with 5-aminosalicylic acid compounds is the first step in the treatment of mild to moderately active UC. Corticosteroids, such as prednisolone are used in UC patients with moderate to severe disease activity, but only for remission induction therapy because of side effects associated with long-term use...
May 12, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29752413/everolimus-with-reduced-calcineurin-inhibitor-exposure-in-renal-transplantation
#20
Julio Pascual, Stefan P Berger, Oliver Witzke, Helio Tedesco, Shamkant Mulgaonkar, Yasir Qazi, Steven Chadban, Federico Oppenheimer, Claudia Sommerer, Rainer Oberbauer, Yoshihiko Watarai, Christophe Legendre, Franco Citterio, Mitchell Henry, Titte R Srinivas, Wen-Lin Luo, AnaMaria Marti, Peter Bernhardt, Flavio Vincenti
Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1...
May 11, 2018: Journal of the American Society of Nephrology: JASN
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