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Calcineurin inhibitor

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https://www.readbyqxmd.com/read/28094770/rapamycin-mediated-mtor-inhibition-uncouples-hiv-1-latency-reversal-from-cytokine-associated-toxicity
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28051798/%C3%A2-conversion-to-mycophenolate-mofetil-monotherapy-in-liver-recipients-calcineurin-inhibitor-levels-are-key
#14
Blanca Norero, Carolina A Serrano, Alberto Sanchez-Fueyo, Ignacio Duarte, Javiera Torres, Mauricio Ocquetau, Francisco Barrera, Marco Arrese, Alejandro Soza, Carlos Benítez
 The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28042353/immunosuppressive-therapy-after-solid-organ-transplantation-does-the-intermed-identify-patients-at-risk-of-poor-adherence
#15
Laurent Michaud, Gundula Ludwig, Sylvie Berney, Stéphanie Rodrigues, Anne Niquille, Valérie Santschi, Anne-Sophie Favre, Anne-Catherine Lange, Annemieke A Michels, Bernard Vrijens, Olivier Bugnon, Nathalie Pilon, Manuel Pascual, Jean-Pierre Venetz, Friedrich Stiefel, Marie-Paule Schneider
BACKGROUND: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT) recipients. OBJECTIVE: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20) might have lower medication adherence than noncomplex patients (INTERMED≤20)...
October 2016: Pharmacy Practice
https://www.readbyqxmd.com/read/28041666/prediabetes-in-pediatric-recipients-of-liver-transplant-mechanism-and-risk-factors
#16
Emily R Perito, Robert H Lustig, Philip Rosenthal
OBJECTIVE: To investigate the role of calcineurin inhibitor exposure and states of insulin resistance-obesity and adolescence-in prediabetes after pediatric liver transplant via oral glucose tolerance testing, which previously has not been done systematically in these at-risk youths. STUDY DESIGN: This was a cross-sectional study of 81 pediatric recipients of liver transplant. Prediabetes was defined as impaired glucose tolerance (IGT; glucose ≥140 mg/dL at 2 hours) or impaired fasting glucose (IFG, ≥100 mg/dL)...
December 29, 2016: Journal of Pediatrics
https://www.readbyqxmd.com/read/28040832/renal-transplantation-outcomes-following-heart-and-heart-lung-transplantation
#17
L Wong, Y R Chee, D G Healy, J J Egan, D M Sadlier, Y M O'Meara
BACKGROUND: Chronic kidney disease is a frequent complication following heart and combined heart-lung transplantation. The aim of this study was to analyse the outcome of a subsequent renal transplant in heart, lung and heart-lung transplantation recipients. METHODS: All heart, lung and heart-lung transplant recipients who received a subsequent renal transplant over a 27-year period in a national heart and lung transplant centre were included in this study. RESULTS: A total of 18 patients who had previously undergone heart (n = 6), lung (n = 7) and heart-lung (n = 5) transplantation received a renal transplant...
December 31, 2016: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28035723/tacrolimus-improves-proteinuria-remission-in-adults-with-cyclosporine-a-resistant-or-dependent-minimal-change-disease
#18
Dechao Xu, Xiang Gao, Rongrong Bian, Changlin Mei, Chenggang Xu
AIMS: Cyclosporin A (CsA) is considered as an effective treatment option for steroid-resistant or-dependent patients with adult-onset minimal change disease (MCD). However, CsA resistance or dependence is also observed in these patients. Tacrolimus (TAC) is a calcineurin inhibitor that is potent in cytokine suppression. The authors aim to evaluate the efficacy and safety of TAC therapy in CsA-resistant and-dependent adult-onset MCD patients. METHODS: Patients with adult-onset MCD were enrolled in our department from 2008 to 2012...
December 30, 2016: Nephrology
https://www.readbyqxmd.com/read/28029732/the-efficacy-of-aloe-vera-in-management-of-oral-lichen-planus-a-systematic-review-and-meta-analysis
#19
REVIEW
Shereen Ali, Walaa Wahbi
OBJECTIVES: The main objective of oral lichen planus management is to control symptomatic outbreaks via eliminating lesions and alleviating symptoms. Corticosteroids; calcineurin inhibitors and most of the available modalities are associated with adverse effects which may limit their use. The aim of this review was to assess the effect of Aloe Vera on pain alleviation and/or clinical improvement in patients with symptomatic oral lichen planus. METHODS: MEDLINE-PubMed; CENTRAL and LILACS were searched in May, 2016 to identify all clinical trials evaluating Aloe Vera versus placebo or corticosteroids for treatment of oral lichen planus...
December 28, 2016: Oral Diseases
https://www.readbyqxmd.com/read/28028691/sirolimus-therapy-is-associated-with-elevation-in-circulating-pcsk9-levels-in-cardiac-transplant-patients
#20
Vinaya Simha, Sisi Qin, Pankaj Shah, Byron H Smith, Walter K Kremers, Sudhir Kushwaha, Liewei Wang, Naveen L Pereira
Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p = 0...
December 27, 2016: Journal of Cardiovascular Translational Research
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