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Calcineurin inhibitors

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https://www.readbyqxmd.com/read/28107397/efficacy-and-safety-of-everolimus-for-maintenance-immunosuppression-of-kidney-transplantation-a-meta-analysis-of-randomized-controlled-trials
#1
Jinyu Liu, Dong Liu, Juan Li, Lan Zhu, Chengliang Zhang, Kai Lei, Qiling Xu, Ruxu You
BACKGROUND: Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but there is conflicting evidence for this approach. OBJECTIVES: To investigate the benefits and harm from randomized clinical trials (RCTs) involving the conversion from CNI to everolimus after kidney transplantation. METHODS: Databases were searched up to March 2016. Two reviewers independently assessed trials for eligibility and quality, and extracted data...
2017: PloS One
https://www.readbyqxmd.com/read/28104164/clinicopathologic-impact-of-early-medullary-ray-injury-in-patients-following-kidney-transplantation
#2
T Niikura, A Kobayashi, M Kawabe, A Katsuma, T Yamakawa, H Katsumata, A Mafune, Y Nakada, I Yamamoto, Y Tanno, I Ohkido, M Okumi, H Ishida, H Yamamoto, T Yokoo, K Tanabe
BACKGROUND: Previously, we explored the histopathologic characteristics of medullary ray injury (MRI) inducing interstitial fibrosis and tubular atrophy (IF/TA) to determine its etiologies, which include calcineurin inhibitor (CNI) toxicity and urologic complications. However, we did not examine the effects of these etiologies on long-term kidney allograft prognosis, because biopsy timing differed among cases. AIM: We examined the influence of early MRI on kidney allograft prognosis using protocol biopsies taken within a 3-month time frame...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104155/immunosuppression-modification-by-everolimus-with-minimization-of-calcineurin-inhibitors-recovers-kidney-graft-function-even-in-patients-with-very-late-conversion-and-also-with-poor-graft-function
#3
M Nojima, Y Yamada, Y Higuchi, K Shimatani, A Kanematsu, S Yamamoto
BACKGROUND: Although kidney graft survival within 5 years after transplantation is now achieved in >95% of recipients, chronic graft deterioration remains a factor limiting long-term survival. Chronic nephrotoxicity induced by calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury; thus, minimization of CNIs by administration of everolimus (EVR) is expected to relieve their toxic effects. METHODS: Fifty-six kidney transplant recipients receiving CNI-based immunosuppression (tacrolimus, n = 34; cyclosporine, n = 22) were analyzed...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104152/experience-of-quatro-therapy-with-everolimus-to-minimize-calcineurin-inhibitor-for-kidney-transplant-recipients
#4
N Nakamura, T Miyazaki, H Matsuzaki, R Furuya, S Miyajima, S Irie, H Matsuoka, M Tanaka
BACKGROUND: This study was divided into three phases, on the occasion of the introduction of everolimus (EVR) in our hospital. METHODS: In the first phase, a study group of six maintenance patients (three living related donors, three deceased donors) who had a history of malignant disease with less than 500 mg/day of proteinuria were enrolled; a high serum creatinine and upper limit of duration after kidney transplant operation was not considered. EVR was discontinued in four of the six patients because of side effects or worsening renal function...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104136/acute-calcineurin-inhibitor-nephrotoxicity-secondary-to-turmeric-intake-a-case-report
#5
A Nayeri, S Wu, E Adams, C Tanner, J Meshman, I Saini, W Reid
Tacrolimus, also known as FK-506, is a potent immunosuppressant agent with a host of drug-drug and food-drug interactions. We present the first case of a probable food-drug interaction between the herb turmeric and tacrolimus leading to acute calcineurin inhibitor nephrotoxicity. A 56-year-old man with a history of orthotopic liver transplantation presented to the emergency department from the clinic with worsening edema in the setting of an elevated creatinine level of 4.2 mg/dL. Before the current presentation, the patient had been recently discharged on a previously tolerated low-dose regimen of tacrolimus with a whole-blood tacrolimus level within the desired range...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104134/eculizumab-and-belatacept-for-de-novo-atypical-hemolytic-uremic-syndrome-associated-with-cfhr3-cfhr1-deletion-in-a-kidney-transplant-recipient-a-case-report
#6
P Dedhia, A Govil, G Mogilishetty, R R Alloway, E S Woodle, B G Abu Jawdeh
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is associated with significant morbidity and mortality and occurs due to genetic or acquired abnormalities that result in the dysregulation of the alternative complement pathway. CASE REPORT: We report a case of post-living kidney transplantation de novo aHUS in a setting of heterozygous deletion in the complement factor H-related protein (CFHR)3-CFHR1 gene. The aHUS episode was possibly triggered by antibody-mediated rejection or tacrolimus...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104127/calcineurin-inhibitor-induced-pain-syndrome-in-abo-incompatible-living-kidney-transplantation-a-case-report
#7
S Ishida, M Kato, T Fujita, Y Funahashi, N Sassa, Y Matsukawa, Y Yoshino, T Yamamoto, T Katsuno, S Maruyama, M Gotoh
BACKGROUND: Calcineurin-inhibitor-induced pain syndrome (CIPS) was used as a reference in the literature as reflex sympathetic dystrophy syndrome related to calcineurin inhibitors. Much of the literature describes CIPS that occurred after kidney and bone marrow transplantation. We describe a rare case of CIPS in induction immunosuppression before kidney transplantation, under administration of an anti-rheumatoid drug. METHODS: A 53-year-old woman had pre-status of ABO-incompatible living kidney transplantation...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28094770/rapamycin-mediated-mtor-inhibition-uncouples-hiv-1-latency-reversal-from-cytokine-associated-toxicity
#8
Alyssa R Martin, Ross A Pollack, Adam Capoferri, Richard F Ambinder, Christine M Durand, Robert F Siliciano
Current strategies for HIV-1 eradication require the reactivation of latent HIV-1 in resting CD4+ T cells (rCD4s). Global T cell activation is a well-characterized means of inducing HIV-1 transcription, but is considered too toxic for clinical applications. Here, we have explored a strategy that involves a combination of immune activation and the immunosuppressive mTOR inhibitor rapamycin. In purified rCD4s from HIV-1-infected individuals on antiretroviral therapy, rapamycin treatment downregulated markers of toxicity, including proinflammatory cytokine release and cellular proliferation that were induced after potent T cell activation using αCD3/αCD28 antibodies...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28092350/long-term-renal-survival-in-patients-undergoing-t-cell-depleted-versus-conventional-hematopoietic-stem-cell-transplants
#9
I G Glezerman, S Devlin, M Maloy, M Bui, E A Jaimes, S A Giralt, A A Jakubowski
Calcineurin inhibitor (CNI)-sparing T-cell depleted (TCD) hematopoietic stem cell transplants (HSCTs) are presumed to be less nephrotoxic than conventional HSCTs. We evaluated incidence and risk factors for kidney failure and chronic kidney disease (CKD) in 231 TCD and 212 conventional HSCT recipients. Kidney failure required a median glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) for ⩾100 days anytime after 180-days post-HSCT. Two-year cumulative incidence (CI) of kidney failure was 42% in the conventional versus 31% in the TCD group (P=0...
January 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28090570/targeted-inhibition-of-pancreatic-acinar-cell-calcineurin-is-a-novel-strategy-to-prevent-post-ercp-pancreatitis
#10
Abrahim I Orabi, Li Wen, Tanveer A Javed, Tianming Le, Ping Guo, Subramaniam Sanker, David Ricks, Kristy Boggs, John F Eisses, Carlos Castro, Xiangwei Xiao, Krishna Prasadan, Farzad Esni, George K Gittes, Sohail Z Husain
BACKGROUND AND AIMS: There is a pressing need to develop effective preventative therapies for post-ERCP pancreatitis (PEP). We demonstrated that early PEP events are induced through the calcium-activated phosphatase calcineurin and that global calcineurin deletion abolishes PEP in mice. A crucial question is whether acinar cell calcineurin controls the initiation of PEP in vivo. METHODS: We used a mouse model of PEP and examined the effects of in vivo acinar cell-specific calcineurin deletion by either generating a conditional knockout line or infusing a novel AAV-Ela-iCre into the pancreatic duct of a calcineurin floxed line...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28079600/acute-administration-of-cyclosporine-a-does-not-impair-attention-or-memory-performance-in-healthy-men
#11
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
#12
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/28073178/polyclonal-and-monoclonal-antibodies-for-induction-therapy-in-kidney-transplant-recipients
#13
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
#14
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
#15
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/28061453/the-regulator-of-calcineurin-1-rcan1-inhibits-nuclear-factor-kappab-signaling-pathway-and-suppresses-human-malignant-glioma-cells-growth
#16
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
#17
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
#18
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
#19
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
#20
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
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