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Calcineurin inhibitors

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https://www.readbyqxmd.com/read/28724911/honokiol-inhibits-c-met-ho-1-tumor-promoting-pathway-and-its-cross-talk-with-calcineurin-inhibitor-mediated-renal-cancer-growth
#1
Murugabaskar Balan, Samik Chakraborty, Evelyn Flynn, David Zurakowski, Soumitro Pal
Honokiol (HNK) is a small molecule with potent anti-inflammatory and anti-tumorigenic properties; yet the molecular targets of HNK are not well studied. Hyperactivation of the receptor tyrosine kinase c-Met and overexpression of the cytoprotective enzyme heme oxygenase-1 (HO-1) play a critical role in the growth and progression of renal cell carcinoma (RCC). Interestingly, the calcineurin inhibitor (CNI) cyclosporine A (CsA), an immunosuppressant used to prevent allograft rejection, can also increase the risk of RCC in transplant patients...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714558/everolimus-and-reduced-calcineurin-inhibitor-therapy-in-pediatric-liver-transplant-recipients-results-from-a-multicenter-prospective-study
#2
Rainer Ganschow, Bo-Goran Ericzon, Anil Dhawan, Khalid Sharif, El-Djouher Martzloff, Barbara Rauer, Jennifer Ng, Patricia Lopez
In a 24-month, multicenter, single-arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1-6 months post-transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment-related serious infections leading to hospitalization and premature study drug discontinuation...
July 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28710230/the-tissue-reconstructing-ability-of-colon-cscs-is-enhanced-by-fk506-and-suppressed-by-gsk3-inhibition
#3
Ryo Ishida, Michiyo Koyanagi-Aoi, Nobu Oshima, Yoshihiro Kakeji, Takashi Aoi
Cancer stem cells (CSCs) are capable of reconstructing cancer tissues, are involved in both recurrence and metastasis, and contribute to therapeutic resistance. Therefore, elucidating the molecular mechanism in CSCs is important to successfully treat unresectable cancers. Previously we observed that colon cancer stem-like cells can be induced from human colon cancer cell lines by retrovirally introducing OCT3/4, SOX2 and KLF4, and we have designated such cells as induced cancer stem cells (iCSCs). In the current study, we used iCSCs to evaluate the molecular mechanism of colon CSCs and developed new methods to control them...
July 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28708333/conversion-from-calcineurin-inhibitors-to-mtor-inhibitors-as-primary-immunosuppressive-drugs-in-pediatric-heart-transplantation
#4
Alfred Asante-Korang, Jennifer Carapellucci, Diane Krasnopero, Abigail Doyle, Brian Brown, Ernest Amankwah
There are only a few reports of successful use of mammalian target of rapamycin (mTORI) as primary immunosuppression in pediatric heart transplantation. Compared to calcineurin inhibitors, mTORI have less side effects, especially nephrotoxicity, infections and malignancies. A retrospective study was conducted at our institution of all 170 heart transplants from 1995-2015. Nineteen patients were switched from tacrolimus(n=15) or cyclosporin(n=4) to everolimus(n=4) or sirolimus(n=15) due to nephrotoxicity(n=5), malignancy(n=8), EBV viremia/reactive plasmacytic changes(n=5) and immune hemolytic anemia(n=1)...
July 14, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28706974/sirolimus-increases-t-cell-abundance-in-the-sun-exposed-skin-of-kidney-transplant-recipients
#5
Michael Thomas Burke, Lauren C Sambira Nahum, Nicole M Isbel, Robert P Carroll, Hans Peter Soyer, Ross Francis, Jennifer Anne Bridge, Carmel Hawley, Kimberly Oliver, Christine E Staatz, James William Wells
BACKGROUND: Kidney transplant recipients (KTRs) receiving the mammalian target of rapamycin inhibitor sirolimus may display a reduced risk of skin cancer development compared to KTRs receiving calcineurin inhibitors. Despite studies investigating the effects of these 2 drug classes on T cells in patient blood, the effect these drugs may have in patient skin is not yet known. METHODS: Fifteen patients with chronic kidney disease (not recipients of immunosuppressive drugs), and 30 KTRs (15 receiving a calcineurin inhibitor, and 15 receiving sirolimus) provided matched samples of blood, sun exposed (SE) and non-SE skin...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28703786/fistulizing-crohn-s-disease
#6
Michael Scharl, Gerhard Rogler, Luc Biedermann
Fistulas still represent one of the most important complications in patients with Crohn's disease (CD). At least one third of CD patients suffer from fistulas during their disease course and amongst them longstanding remission of complex fistulas occurs only in about one third. So far, fistula pathogenesis is only partially understood. From a histopathological view, a fistula is a tube covered by flat epithelial cells. Current research suggests that the driving force for fistula development is epithelial-to-mesenchymal transition (EMT)...
July 13, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28697720/early-onset-pneumonia-after-liver-transplant-microbial-causes-risk-factors-and-outcomes-mansoura-university-egypt-experience
#7
Mohammad Khairy El-Badrawy, Raed El-Metwaly Ali, Amr Yassen, Mohammad Ahmad AbouElela, Rehab Ahmad Elmorsey
OBJECTIVES: Pneumonia has a negative effect on the outcome of liver transplant. Our aim was to analyze early-onset pneumonia that developed within the first month after transplant. MATERIALS AND METHODS: This prospective single-center study included 56 adult living-donor liver transplant recipients; those who developed early-onset pneumonia based on clinical and radiologic criteria were investigated as to causative pathogens and then followed up and compared with other recipients without pneumonia to illustrate risk factors, outcomes, and related mortality of posttransplant pneumonia...
July 11, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28695412/-basis-for-the-treatment-of-eczematous-diseases-in-otorhinolaryngology
#8
REVIEW
R Fölster-Holst, A Sperl, T Albrecht, L Klimek
According to Coombs and Gell, cell-mediated immune responses belong to type IV reactions and are borne mainly by T lymphocytes. The eliciting allergens are usually so-called haptens. Haptens are substances which develop to whole antigens only by binding to protein carriers. In otorhinolaryngology, delayed allergic hypersensitivities are apparent mainly as contact eczemata. Facial dermatitis, auricle and ear canal eczema as well as perioral eczema belong to the most common forms of contact dermatitis in ENT patients...
July 10, 2017: HNO
https://www.readbyqxmd.com/read/28693446/response-to-immunosuppressive-therapy-in-pla2r-associated-and-non-pla2r-associated-idiopathic-membranous-nephropathy-a-retrospective-multicenter-cohort-study
#9
Jia Wang, Qionghong Xie, Zhuxing Sun, Ningxin Xu, Yan Li, Liang Wang, Shaojun Liu, Jun Xue, Chuan-Ming Hao
BACKGROUND: According to renal M type phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (IMN) could be categorized into PLA2R-associated and non-PLA2R-associated IMN. We conducted a retrospective, multicenter cohort study with 91 patients to compare the effect of immunosuppressive therapy between PLA2R-associated and non-PLA2R-associated IMN patients. METHODS: A total of 91 biopsy-proven IMN patients from Huashan hospital and People's Hospital of Wuxi in past 5 years were collected into this study...
July 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28691954/maintenance-belatacept-based-immunosuppression-in-lung-transplantation-recipients-who-failed-calcineurin-inhibitors
#10
Carlo J Iasella, Ryan J Winstead, Cody A Moore, Bruce A Johnson, Ayelet T Feinberg, Matthew R Morrell, J W Awori Hayanga, Elizabeth A Lendermon, Adriana Zeevi, John F McDyer, Christopher R Ensor
BACKGROUND: Traditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lacks data in lung transplantation. This series aims to describe the response to belatacept ISR in 11 lung transplantation recipients after CNI failure. METHODS: Single center, retrospective medical record review of adult lung transplant recipients (LTR) before and after conversion to belatacept-based ISR...
July 6, 2017: Transplantation
https://www.readbyqxmd.com/read/28686294/nfat-regulated-cytokine-gene-expression-during-tacrolimus-therapy-early-after-renal-transplantation
#11
Sara Bremer, Nils T Vethe, Morten Skauby, Margrete Kasbo, Elisabet D Johansson, Karsten Midtvedt, Stein Bergan
AIMS: Despite pharmacokinetic monitoring of calcineurin inhibitors, the long-term outcome after transplantation (Tx) is still hampered by the side effects of these drugs. The aim of this study was to characterize the nuclear factor of activated T cells (NFAT)-regulated gene expression as a potential pharmacodynamic biomarker for further individualization of tacrolimus (Tac) therapy. METHODS: In 29 renal allograft recipients samples were drawn once pre-Tx, and before and 1...
July 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28684310/selective-inhibition-of-plasma-membrane-calcium-atpase-4-improves-angiogenesis-and-vascular-reperfusion
#12
Sathishkumar Kurusamy, Dolores López-Maderuelo, Robert Little, David Cadagan, Aaron M Savage, Jude C Ihugba, Rhiannon R Baggott, Farjana B Rowther, Sara Martínez-Martínez, Pablo Gómez-Del Arco, Clare Murcott, Weiguang Wang, J Francisco Nistal, Delvac Oceandy, Ludwig Neyses, Robert N Wilkinson, Elizabeth J Cartwright, Juan Miguel Redondo, Angel Luis Armesilla
AIMS: Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activity in the ischaemic organ remains a major problem in current pro-angiogenic therapeutic approaches. Plasma membrane calcium ATPase 4 (PMCA4) negatively regulates VEGF-activated angiogenesis via inhibition of the calcineurin/NFAT signalling pathway...
July 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28682561/-immunosuppression-in-kidney-transplantation-a-way-between-efficacy-and-toxicity
#13
Costanza Casati, Alberto Menegotto, Maria Luisa Querques, Federica Ravera, Giacomo Colussi
Renal transplantation is the best treatment for patients with end-stage renal disease. Over the last decades, the introduction of new immunosuppressive agents resulted into the reduction of the incidence of acute rejection and early graft loss. Despite this progress, there has been little improvement in the average life of the transplant. The main reasons of late failure are patient's death due to several complications (e.g. cancer, infectious or metabolic), and progressive deterioration of renal function caused by immunological and non-immunological factors...
April 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28671378/acute-and-chronic-paronychia
#14
Jeff C Leggit
Paronychia is inflammation of the fingers or toes in one or more of the three nail folds. Acute paronychia is caused by polymicrobial infections after the protective nail barrier has been breached. Treatment consists of warm soaks with or without Burow solution or 1% acetic acid. Topical antibiotics should be used with or without topical steroids when simple soaks do not relieve the inflammation. The presence of an abscess should be determined, which mandates drainage. There are a variety of options for drainage, ranging from instrumentation with a hypodermic needle to a wide incision with a scalpel...
July 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28669992/treatment-of-membranous-nephropathy-time-for-a-paradigm-shift
#15
REVIEW
Piero Ruggenenti, Fernando C Fervenza, Giuseppe Remuzzi
In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition...
July 3, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28663197/the-subcellular-distribution-of-hdac1-in-neurotoxic-conditions-is-dependent-on-serine-phosphorylation
#16
Yunjiao Zhu, Oscar G Vidaurre, Kadidia P Adula, Nebojsa Kezunovic, Maureen Wentling, George W Huntley, Patrizia Casaccia
Calcium-dependent nuclear export of HDAC1 was previously shown to precede axonal damage in culture, but the in vivo relevance of these findings and the potential post-translational modifications of HDAC1 remained elusive. Using acute hippocampal slices from mice of either sex, with genetic conditional ablation of Hdac1 in CA1 hippocampal neurons (i.e. Camk2a-cre;Hdac1(fl/fl) ), we show significantly diminished axonal damage in response to neurotoxic stimuli. The protective effect of Hdac1 ablation was detected also in CA3 neurons in Grik4-cre;Hdac1(fl/f) mice, that were more resistant to the excitotoxic damage induced by intraventricular injection of kainic acid...
June 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28661705/lichen-sclerosus-in-women-a-review
#17
F R Pérez-López, P Vieira-Baptista
Female lichen sclerosus is a chronic inflammatory dermatitis, with a predilection for the anogenital area, which in some cases can become seriously distorted (atrophy of the labia minora, phimosis, introital stenosis, etc.). Most cases are diagnosed in postmenopausal women, but it can affect women of any age. Lichen sclerosus is usually a pruriginous condition, although it can also be asymptomatic. It is associated with an increased risk of vulvar cancer, even though it is not a premalignant condition itself...
August 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/28654710/nonpharmacologic-strategies-and-topical-agents-for-treating-atopic-dermatitis-an-update
#18
Linda F Stein Gold, Lawrence F Eichenfield
The signs and symptoms of atopic dermatitis can be safely and effectively controlled in most patients; in many cases, the disease can be improved to the point that signs and symptoms are absent or minimal. In addition, flares can be effectively controlled and, in some cases, prevented. New topical medications, improved strategies for the use of topical corticosteroids and topical calcineurin inhibitors, and judicious use of nonpharmacologic regimens-including bathing, bleach baths, and early use of emollients-have led to better disease management and improved quality of life for patients and their families...
March 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28652705/renal-function-in-heart-transplant-patients-after-switch-to-combined-mammalian-target-of-rapamycin-inhibitor-and-calcineurin-inhibitor-therapy
#19
Matthias Helmschrott, Rasmus Rivinius, Thomas Bruckner, Hugo A Katus, Andreas O Doesch
BACKGROUND: A calcineurin inhibitor (CNI)-based immunosuppression combined with mammalian target of rapamycin inhibitors (mTORs) seems to be attractive in patients after heart transplantation (HTX) in special clinical situations, for example, in patients with adverse drug effects of prior immunosuppression. Previous studies in patients after HTX detected advantageous effects regarding renal function of a tacrolimus (TAC)-based vs cyclosporine-A (CSA)-based immunosuppression (in combination with mycophenolate mofetil)...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28648516/-mycosis-fungoides-in-a-heart-transplant-recipient
#20
Q Bodard, N Litrowski, D Carre, M Midhat, P Chenal, P Bravard
BACKGROUND: Skin cancer occurs frequently in organ transplant patients as a result of induced immunosuppression. Most cases involve carcinomas or B-cell lymphomas induced by the Epstein Barr virus (EBV). Cutaneous T-cell lymphomas remain rare. We report a case of cutaneous T-cell lymphoma of the mycosis fungoides type in a heart transplant recipient. PATIENTS AND METHODS: A 68-year-old man who had received a heart transplant 21years earlier and was being treated with tacrolimus, mycophenolate mofetil and prednisolone had been presenting a psoriasiform rash on his trunk, limbs and head for 4years...
June 22, 2017: Annales de Dermatologie et de Vénéréologie
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