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Calcineurin inhibitors

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https://www.readbyqxmd.com/read/28805561/kcnj11-and-kcnq1-gene-polymorphisms-are-not-associated-with-post-transplant-diabetes-mellitus-in-kidney-allograft-recipients-treated-with-tacrolimus
#1
E Dabrowska-Zamojcin, M Tarnowski, M Szydlowski, M Romanowski, V Dziedziejko, K Safranow, L Domanski, A Pawlik
Post-transplant diabetes mellitus (PTDM) is a metabolic disorder occurring after solid organ transplantation during the therapy with calcineurin inhibitors. ATP-sensitive potassium channels KCNJ11 and KCNQ1 play an important role in the regulation of insulin secretion by β cells and development of diabetes mellitus. Numerous studies have confirmed the association between KCNJ11 and KCNQ1 gene polymorphisms and type 2 diabetes. The aim of this study was to examine the association between KCNJ11 and KCNQ1 gene polymorphisms and posttransplant diabetes mellitus in kidney allograft recipients treated with tacrolimus...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28795147/impact-of-the-trough-level-of-calcineurin-inhibitor-on-the-prevalence-of-donor-specific-human-leukocyte-antigen-antibodies-during-long-term-follow-up-after-pediatric-liver-transplantation-antibody-strength-and-complement-binding-ability
#2
Kazuaki Tokodai, Shigehito Miyagi, Chikashi Nakanishi, Yasuyuki Hara, Wataru Nakanishi, Masafumi Goto, Michiaki Unno, Takashi Kamei
BACKGROUND: In pediatric patients, long-term immunosuppression after liver transplantation (LT) is typically minimal. However, posttransplant donor-specific HLA antibodies (DSAs) may be prevalent under these conditions. Here, we evaluated the effects of minimized calcineurin inhibitor (CNI) on DSA development to assess the validity of minimized/withdrawn immunosuppression. METHODS: We retrospectively examined 66 patients who underwent pediatric LT at our institution between July 1991 and October 2013...
August 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28791279/pneumocystis-jirovecii-pneumonia-in-pediatric-inflammatory-bowel-disease-a-case-report-and-literature-review
#3
Sally J Lawrence, Manish Sadarangani, Kevan Jacobson
Immunosuppressive therapy is a known risk factor for opportunistic infections. We report the first case of severe Pneumocystis jirovecii infection requiring intensive care in a pediatric patient with inflammatory bowel disease (IBD). The literature was reviewed and there were 92 reported cases of Pneumocystis pneumonia (PCP) in patients with IBD. Most sources were case reports and there was likely reporting bias toward patients receiving immunomodulators, anti-tumor necrosis factor (anti-TNF) therapy, and those who died...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28789575/prescriptions-for-atopic-dermatitis-oral-corticosteroids-remain-commonplace
#4
Tiffany Alexander, Elena Maxim, Leah A Cardwell, Aneesh Chawla, Steven R Feldman
INTRODUCTION: Atopic dermatitis (AD) is a common, chronic inflammatory skin disease characterized by pruritic, often lichenified, patches and plaques. METHODS: Data were obtained from the Humana database, a large claims-based database encompassing more than 20 million patients under a commercial healthcare insurance plan. Our cohort included 39,526 subjects who saw a dermatologist for a primary ICD-9 diagnosis of atopic dermatitis (691.8) between the years of 2010-2015...
August 9, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28783148/clinical-characteristics-and-outcome-of-human-herpesvirus-6-encephalitis-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
M Ogata, K Oshima, T Ikebe, K Takano, H Kanamori, T Kondo, Y Ueda, T Mori, H Hashimoto, H Ogawa, T Eto, T Ueki, T Miyamoto, T Ichinohe, Y Atsuta, T Fukuda
In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11...
August 7, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28774273/thrombotic-microangiopathy-associated-with-valproic-acid-toxicity
#6
Sean A Hebert, Timothy P Bohan, Christian L Erikson, Rita D Swinford
BACKGROUND: Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA...
August 3, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28762681/-novel-antiviral-agents-for-the-treatment-of-hcv-among-renal-transplant-recipients
#7
REVIEW
Fabrizio Fabrizi, Francesca M Donato, Piergiorgio Messa
The frequency of hepatitis C virus infection remains high in renal transplant recipients and plays a detrimental role on survival in this population. According to the latest evidence, the adjusted relative risk of mortality and graft loss for anti-HCV seropositive versus anti-HCV negative renal transplant recipients was 1.85 with a 95% confidence interval (CI) of 1.49 ; 2.31 (P < 0.0001) and 1.76 (95% CI, 1.46 ; 2.11) (P < 0.0001), respectively. Interferon-based regimens have been recommended for the treatment of hepatitis C after renal transplantation only in selected circumstances because of an increased risk of acute rejection due to the immuno-stimulatory properties of interferon...
August 1, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28761977/calcineurin-inhibitors-regulate-fibroblast-growth-factor-23-fgf23-synthesis
#8
Ludmilla Bär, Claudia Großmann, Michael Gekle, Michael Föller
Fibroblast growth factor 23 (FGF23) inhibits renal phosphate reabsorption and calcitriol formation, effects depending on Klotho as a co-receptor for FGF23. In addition, FGF23/Klotho strongly influences aging and the onset of age-associated diseases. The synthesis of FGF23 by bone cells is induced by store-operated Ca(2+) entry (SOCE) through Orai1 in UMR106 osteoblast-like cells. Ca(2+) entry activates the phosphatase calcineurin in many cell types which dephosphorylates nuclear factor of activated T cells (NFAT) thereby stimulating its transcriptional activity...
July 31, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28761838/topical-therapies-in-psoriasis
#9
REVIEW
R Torsekar, Manjyot M Gautam
Topical therapy as monotherapy is useful in psoriasis patients with mild disease. Topical agents are also used as adjuvant for moderate-to-severe disease who are being concurrently treated with either ultraviolet light or systemic medications. Emollients are useful adjuncts to the treatment of psoriasis. Use of older topical agents such as anthralin and coal tar has declined over the years. However, they are cheaper and can still be used for the treatment of difficult psoriasis refractory to conventional treatment...
July 2017: Indian Dermatology Online Journal
https://www.readbyqxmd.com/read/28761769/tacrolimus-induced-type-iv-renal-tubular-acidosis-following-liver-transplantation
#10
Christopher Schmoyer, Suraj Mishra, Frank Fulco
Calcineurin inhibitors remain an integral component of immunosuppressive therapy regimens following solid organ transplantation. Although nephrotoxicity associated with these agents is well documented, type IV renal tubular acidosis is a rare and potentially underreported complication following liver transplantation. Hepatologists must be able to recognize this adverse effect as it can lead to fatal hyperkalemia. We describe a case of tacrolimus-induced hyperkalemic type IV renal tubular acidosis in a patient following an orthotopic liver transplant for alcoholic cirrhosis...
2017: Case Reports in Hepatology
https://www.readbyqxmd.com/read/28761179/soluble-epoxide-hydrolase-inhibition-protected-against-angiotensin-ii-induced-adventitial-remodeling
#11
Chi Zhou, Jin Huang, Qing Li, Jiali Nie, Xizhen Xu, Dao Wen Wang
Epoxyeicosatrienoic acids (EETs), the metabolites of cytochrome P450 epoxygenases derived from arachidonic acid, exert important biological activities in maintaining cardiovascular homeostasis. Soluble epoxide hydrolase (sEH) hydrolyzes EETs to less biologically active dihydroxyeicosatrienoic acids. However, the effects of sEH inhibition on adventitial remodeling remain inconclusive. In this study, the adventitial remodeling model was established by continuous Ang II infusion for 2 weeks in C57BL/6 J mice, before which sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered by gavage...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759009/ginseng-extract-reduces-tacrolimus-induced-oxidative-stress-by-modulating-autophagy-in-pancreatic-beta-cells
#12
Sun Woo Lim, Long Jin, Kang Luo, Jian Jin, Chul Woo Yang
We previously reported that long-term treatment with a calcineurin inhibitor impairs autophagy process in pancreatic beta cells. This study investigated the effect of Korean red ginseng extract (KRGE) on autophagy modulated by oxidative stress. In mice with tacrolimus (Tac)-induced diabetes mellitus, KRGE alleviated islet dysfunction and decreased oxidative stress and autophagic vacuoles. In vitro, KRGE decreased autophagosome formation and attenuated lysosomal degradation, accompanied by improved beta cell viability and insulin secretion...
July 31, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28750002/dna-pkcs-controls-calcineurin-mediated-il-2-production-in-t-lymphocytes
#13
Ara Kim Wiese, Marie Schluterman Burdine, Richard H Turnage, Alan J Tackett, Lyle J Burdine
Loss of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity in mammals results in severe combined immuno-deficiency (SCID). This SCID phenotype has been postulated to be due solely to the function of DNA-PKcs in V(D)J recombination, a process critical for lymphocyte maturation. However; we show that DNA-PKcs is required for IL-2 production via regulation of the calcineurin signaling pathway. Reducing DNA-PKcs activity in activated T cells either by shRNA or an inhibitor significantly reduced IL-2 production by blocking calcineurin activity and the translocation of NFAT into the nucleus...
2017: PloS One
https://www.readbyqxmd.com/read/28748621/outcomes-of-matched-sibling-donor-bone-marrow-transplantation-in-children-using-single-agent-calcineurin-inhibitors-as-prophylaxis-for-graft-versus-host-disease
#14
Caitlin W Elgarten, Danielle E Arnold, Nancy J Bunin, Alix E Seif
BACKGROUND: Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI may be sufficient prophylaxis for a defined group of patients. Single-agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years...
July 27, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28746924/cyclin-dependent-kinase-inhibitor-p21waf1-cip1-facilitates-the-development-of-cardiac-hypertrophy
#15
Yang-Fei Tong, Yan Wang, Yuan-Yuan Ding, Jing-Mei Li, Xi-Chun Pan, Xiao-Lan Lu, Xiao-Hong Chen, Ya Liu, Hai-Gang Zhang
BACKGROUND/AIMS: Adult cardiomyocytes can re-enter cell cycle as stimulated by prohypertrophic factors although they withdraw from cell cycle soon after birth. p21WAF1/CIP1, a cyclin-dependent kinase inhibitor, has been implicated in cardiac hypertrophy, however, its precise contribution to this process remains largely unclear. METHODS: The gene expression profile in left ventricle (LV) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined using quantitative PCR array and verified by real-time PCR and Western blotting...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28743539/recommendations-of-everolimus-use-in-liver-transplant
#16
Angel Rubín Suárez, Itxarone Bilbao Aguirre, Javier Fernández-Castroagudin, José Antonio Pons Miñano, Magdalena Salcedo Plaza, Evaristo Varo Pérez, Martín Prieto Castillo
Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles...
July 22, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/28740511/safety-and-tolerance-of-donor-derived-mesenchymal-stem-cells-in-pediatric-living-donor-liver-transplantation-the-mystep1-study
#17
Steffen Hartleif, Michael Schumm, Michaela Döring, Markus Mezger, Peter Lang, Marc H Dahlke, Joachim Riethmüller, Alfred Königsrainer, Rupert Handgretinger, Silvio Nadalin, Ekkehard Sturm
BACKGROUND: Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#18
REVIEW
Krishna M Karpe, Girish S Talaulikar, Giles D Walters
BACKGROUND: Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. OBJECTIVES: This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death...
July 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28730617/methotrexate-for-severe-childhood-atopic-dermatitis-clinical-experience-in-a-tertiary-center
#19
Veronika Dvorakova, Grainne M O'Regan, Alan D Irvine
BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) affects up to 20% of children. Although the majority of patients are adequately controlled using emollients, topical corticosteroids, topical calcineurin inhibitors, or phototherapy, children with moderate to severe AD may require systemic treatment for control. The objective of the current study was to evaluate the efficacy and safety of methotrexate in children with severe AD attending a tertiary referral center. METHODS: A retrospective chart review was undertaken of all children who received methotrexate for severe AD at our tertiary referral center from November 2010 to August 2015...
July 21, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28729555/inhibition-of-phosphodiesterase-5-suppresses-calcineurin-nfat-mediated-trpc6-expression-in-pulmonary-artery-smooth-muscle-cells
#20
Shaojun Li, Yilin Pan, Rui Ke, Xinming Xie, Cui Zhai, Wenhua Shi, Jian Wang, Xin Yan, Limin Chai, Qingting Wang, Qianqian Zhang, Xiaofan Su, Lan Yang, Li Gao, Manxiang Li
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus...
July 20, 2017: Scientific Reports
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