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Calcineurin inhibitors

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https://www.readbyqxmd.com/read/29793020/epha2-stimulates-vcam-1-expression-through-calcium-dependent-nfat1-activity
#1
Steven Daniel Funk, Alexandra C Finney, Arif Yurdagul, Christopher B Pattillo, A Wayne Orr
Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin-A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-κB (NF-κB/p65) and nuclear factor of activated T-cells (NFAT)...
May 21, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29787522/belatacept-in-solid-organ-transplant-review-of-current-literature-across-transplant-types
#2
Caroline P Perez, Neha Patel, Caitlin R Mardis, Holly B Meadows, David J Taber, Nicole A Pilch
Calcineurin inhibitors (CNIs) have been the backbone immunosuppressant for solid organ transplant recipients for decades. Long-term use of CNIs unfortunately is associated with multiple toxicities, with the biggest concern being CNI-induced nephrotoxicity. Belatacept is a novel agent approved for maintenance immunosuppression in renal transplant recipients. In the kidney transplant literature, it has shown promise as being an alternative agent by preserving renal function and having a minimal adverse effect profile...
May 22, 2018: Transplantation
https://www.readbyqxmd.com/read/29786149/national-survey-found-that-managing-childhood-nephrotic-syndrome-in-nigeria-varied-widely-and-did-not-comply-with-the-best-evidence
#3
Christopher I Esezobor, Adanze O Asinobi, Henrietta U Okafor, Rosamund Akuse, Rasheed Gbadegesin
AIM: This study explored any variations in managing childhood nephrotic syndrome between specialist centres in Nigeria and how closely the care reflected the best available evidence. METHODS: In 2016 the heads of Nigerian paediatric nephrology units were asked to complete a study questionnaire that focused on managing nephrotic syndrome. RESULTS: Of the 31 clinicians we approached, 81% returned the completed questionnaire. The majority (64%) had received paediatric nephrology training and 40% had practised for at least 10 years...
May 22, 2018: Acta Paediatrica
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
#4
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
#5
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/29777361/tremor-induced-by-calcineurin-inhibitor-immunosuppression-a-single-centre-observational-study-in-kidney-transplanted-patients
#6
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
#7
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/29771270/effect-of-conversion-from-calcineurin-inhibitors-to-everolimus-on-hepatitis-c-viremia-in-adult-kidney-transplant-recipients
#8
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/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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/29751546/genome-wide-identification-and-analysis-of-arabidopsis-sodium-proton-antiporter-nhx-and-human-sodium-proton-exchanger-nhe-homologs-in-sorghum-bicolor
#16
P Hima Kumari, S Anil Kumar, Katam Ramesh, Palakolanu Sudhakar Reddy, M Nagaraju, A Bhanu Prakash, Trushar Shah, Ashley Henderson, Rakesh K Srivastava, G Rajasheker, A Chitikineni, Rajeev K Varshney, P Rathnagiri, M Lakshmi Narasu, P B Kavi Kishor
Na⁺ transporters play an important role during salt stress and development. The present study is aimed at genome-wide identification, in silico analysis of sodium-proton antiporter (NHX) and sodium-proton exchanger (NHE)-type transporters in Sorghum bicolor and their expression patterns under varied abiotic stress conditions. In Sorghum , seven NHX and nine NHE homologs were identified. Amiloride (a known inhibitor of Na⁺/H⁺ exchanger activity) binding motif was noticed in both types of the transporters...
May 3, 2018: Genes
https://www.readbyqxmd.com/read/29751166/safety-and-efficacy-of-combination-treatment-with-calcineurin-inhibitors-and-vedolizumab-in-patients-with-refractory-inflammatory-bowel-disease
#17
Britt Christensen, Peter Gibson, Dejan Micic, Ruben J Colman, Sarah R Goeppinger, Olufemmi Kassim, Andres Yarur, Christopher R Weber, Russell D Cohen, David T Rubin
BACKGROUND & AIMS: Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohn's disease (CD) or ulcerative colitis (UC). We analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors METHODS: We collected data on patients with CD (n=9) or UC (n=11) who began treatment with vedolizumab from May 20, 2014 through March 30, 2015 and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy...
May 8, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29750772/the-ins-and-outs-of-an-outside-in-view-of-allergies-atopic-dermatitis-and-allergy-prevention
#18
Marcus Shaker, Robert G P Murray, Julianne A Mann
PURPOSE OF REVIEW: The skin barrier is a dynamic innate immune organ. This review summarizes the current understanding of how deficiencies associated with atopic dermatitis invite other atopic disorders of the allergic march. RECENT FINDINGS: Atopic dermatitis is characterized by skin barrier defects (such as mutations in filaggrin), intrinsic proallergic T-helper cell 2 immune dysregulation, and skin microbiome alterations. These factors promote the development of food allergy and asthma...
May 9, 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29750317/mycophenolate-mofetil-for-sustained-remission-in-nephrotic-syndrome
#19
Uwe Querfeld, Lutz T Weber
The clinical application of mycophenolate mofetil (MMF) has significantly widened beyond the prophylaxis of acute and chronic rejections in solid organ transplantation. MMF has been recognized as an excellent treatment option in many immunologic glomerulopathies. For children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS) experiencing steroid toxicity, MMF has been recommended as a steroid-sparing drug. Uncontrolled studies in patients with FRNS and SDSN have shown that many patients can achieve sustained remission of proteinuria with MMF monotherapy...
May 11, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29738315/diagnosis-and-treatment-of-histoplasmosis-in-solid-organ-transplant-patients
#20
Kiran Gajurel, Reshika Dhakal, Stan Deresinski
PURPOSE OF REVIEW: Unlike immunocompetent hosts, solid organ transplant (SOT) recipients with posttransplant histoplasmosis (PTH) often present with disseminated disease and have an attributable mortality of approximately 10%. In this review, we discuss currently available diagnostic tests and treatment strategies in PTH. RECENT FINDINGS: None of the available tests have a 100% diagnostic accuracy. Histoplasma antigen assays are the most sensitive commercially available tests...
May 5, 2018: Current Opinion in Infectious Diseases
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