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https://www.readbyqxmd.com/read/28733752/generic-immunosuppressants
#1
Mara Medeiros, Julia Lumini, Noah Stern, Gilberto Castañeda-Hernández, Guido Filler
Immunosuppressive drugs for solid organ transplantation are critical dose drugs with a narrow therapeutic index. Many of the most commonly used innovator drugs are off patent and have been replicated by generic counterparts, often at substantial cost-savings to the patient. However, serious adverse events caused by the transition from innovator to generic medications, specifically in pediatric solid organ transplant recipients, have questioned these autosubstitutions. The purpose of this review is to summarize the criteria set forth by the regulatory bodies, and to examine how major immunosuppressive drugs conform to these recommendations...
July 21, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28731920/eye-movement-disorders-following-allogeneic-bone-marrow-transplantation-on-fk506-tacrolimus-and-ganciclovir
#2
Barbaros S Karagun, Tugana Akbas, Taner Arpaci, Bulent Antmen
FK506 (tacrolimus) is an immunosuppressive drug and more potent than cyclosporine. FK506 is widely used for immunosuppression in the prevention and treatment of graft-versus-host disease after allogeneic bone marrow transplantation and solid organ transplantation. Neurotoxicity is a recognized complication of FK506 therapy, but ptosis and weakness of eye abduction unilaterally has not been reported in association with FK506 administration to date. We discuss a 13-year-old male patient who developed ptosis and weakness of eye abduction unilaterally 90 days after transplantation with bone marrow from an unrelated donor, for acute lymphoblastic leukemia in this case report...
July 20, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28731207/polyclonal-and-monoclonal-antibodies-for-treating-acute-rejection-episodes-in-kidney-transplant-recipients
#3
REVIEW
Angela C Webster, Sunny Wu, Krishna Tallapragada, Min Young Park, Jeremy R Chapman, Sue J Carr
BACKGROUND: Registry data shows that the incidence of acute rejection has been steadily falling. Approximately 10% to 35% of kidney recipients will undergo treatment for at least one episode of acute rejection within the first post-transplant year. Treatment options include pulsed steroid therapy, the use of an antibody preparation, the alteration of background immunosuppression, or combinations of these options. Over recent years, new treatment strategies have evolved, and in many parts of the world there has been an increase in use of tacrolimus and mycophenolate and a reduction in the use of cyclosporin and azathioprine use as baseline immunosuppression to prevent acute rejection...
July 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28730667/role-of-plasma-exchange-leukocytapheresis-and-plasma-diafiltration-in-management-of-refractory-macrophage-activation-syndrome
#4
Noriko Kinjo, Kazuya Hamada, Chika Hirayama, Masaki Shimizu
Macrophage activation syndrome (MAS) is a life-threating complication of systemic juvenile idiopathic arthritis (s-JIA). Steroid and cyclosporine (CsA) are effective for MAS, but, treatment for steroid- and CsA-resistant patients is still challenging. We report the case of steroid and CsA resistant s-JIA associated MAS misdiagnosed as Kawasaki disease (KD), who was successfully treated with the combination of plasma exchange (PE) and leukocytapheresis (LCAP) followed by plasma diafiltration (PDF). PE + LCAP effectively removed proinflammatory cytokines and reduced the number of peripheral white blood cells...
July 21, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28730378/enzymatic-activity-of-candida-spp-from-oral-cavity-and-urine-in-children-with-nephrotic-syndrome
#5
Dorota Olczak-Kowalczyk, Maria Roszkowska-Blaim, Maria Dąbkowska, Ewa Swoboda-Kopeć, Dariusz Gozdowski, Małgorzata Mizerska-Wasiak, Urszula Demkow, Małgorzata Pańczyk-Tomaszewska
Oral colonization with Candida spp. is not synonymous with a systemic active infection. The aim of the study was to evaluate enzymatic activity of Candida strains isolated from the oral cavity in patients with nephrotic syndrome (NS) and to compare it with the activity determined in urine. We studied 32 children with NS and 26 control healthy children. Children with NS were treated with glucocorticosteroids, cyclosporin A, mycophenolate mofetil or azathioprine. In all children, API-ZYM enzymatic tests were performed to evaluate hydrolytic enzymes of Candida isolated from the oral cavity and in urine...
July 21, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28729910/drug-induced-gingival-hyperplasia-a-retrospective-study-using-spontaneous-reporting-system-databases
#6
Haruna Hatahira, Junko Abe, Yuuki Hane, Toshinobu Matsui, Sayaka Sasaoka, Yumi Motooka, Shiori Hasegawa, Akiho Fukuda, Misa Naganuma, Tomofumi Ohmori, Yasutomi Kinosada, Mitsuhiro Nakamura
BACKGROUND: Drug-induced gingival hyperplasia (DIGH) causes problems with chewing, aesthetics, and pronunciation, and leads to the deterioration of the patient's quality of life (QOL). Thus, the aim of this study was to evaluate the incidence of DIGH using spontaneous reporting system (SRS) databases. METHODS: We analyzed reports of DIGH from SRS databases and calculated the reporting odds ratios (RORs) of suspected drugs (immunosuppressants, calcium channel blockers, and anticonvulsants)...
2017: Journal of Pharmaceutical Health Care and Sciences
https://www.readbyqxmd.com/read/28729555/inhibition-of-phosphodiesterase-5-suppresses-calcineurin-nfat-mediated-trpc6-expression-in-pulmonary-artery-smooth-muscle-cells
#7
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
https://www.readbyqxmd.com/read/28729360/potential-role-of-cyclophilin-a-in-regulating-cytokine-secretion
#8
REVIEW
Farman Ullah Dawar, Yang Xiong, Muhammad Nasir Khan Khattak, Jun Li, Li Lin, Jie Mei
Cyclophilin A (CypA), a peptidylprolyl cis-trans isomerase, is a ubiquitous and multifunctional protein. In addition to its role as a host-cell receptor for cyclosporine A, CypA has diverse functions in inflammatory conditions and diseases. CypA secreted in response to inflammatory stimuli binds to the cell surface via its receptor CD147 and induces secretion of various inflammatory cytokines. However, silencing and inhibition of either CypA or CD147 inhibits inflammatory cytokine expression and inflammation...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729300/rapamycin-is-highly-effective-in-murine-models-of-immune-mediated-bone-marrow-failure
#9
Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28729289/class-ii-eplet-mismatch-modulates-tacrolimus-trough-levels-required-to-prevent-donor-specific-antibody-development
#10
Chris Wiebe, David N Rush, Thomas E Nevins, Patricia E Birk, Tom Blydt-Hansen, Ian W Gibson, Aviva Goldberg, Julie Ho, Martin Karpinski, Denise Pochinco, Atul Sharma, Leroy Storsley, Arthur J Matas, Peter W Nickerson
Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch...
July 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28728917/global-alteration-of-the-drug-binding-pocket-of-human-p-glycoprotein-abcb1-by-substitution-of-fifteen-conserved-residues-reveals-a-negative-correlation-between-substrate-size-and-transport-efficiency
#11
Shahrooz Vahedi, Eduardo E Chufan, Suresh V Ambudkar
P-glycoprotein (P-gp), an ATP-dependent efflux pump, is linked to the development of multidrug resistance in cancer cells. However, the drug-binding sites and translocation pathways of this transporter are not yet well-characterized. We recently demonstrated the important role of tyrosine residues in regulating P-gp ATP hydrolysis via hydrogen bond formations with high affinity modulators. Since tyrosine is both a hydrogen bond donor and acceptor, and non-covalent interactions are key in drug transport, in this study we investigated the global effect of enrichment of tyrosine residues in the drug-binding pocket on the drug binding and transport of P-gp...
July 17, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28725220/a-novel-derivative-of-mycousnine-produced-by-the-endophytic-fungus-mycosphaerella-nawae-exhibits-high-and-selective-immunosuppressive-activity-on-t-cells
#12
Li-Wei Wang, Jin-Liang Wang, Jing Chen, Jia-Jie Chen, Jia-Wei Shen, Xiao-Xiao Feng, Christian P Kubicek, Fu-Cheng Lin, Chu-Long Zhang, Feng-Yang Chen
An endophytic fungus, Mycosphaerella nawae ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages...
2017: Frontiers in Microbiology
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
#13
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/28724844/a-review-of-the-active-treatments-for-toxic-epidermal-necrolysis
#14
Yuri Kinoshita, Hidehisa Saeki
Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction associated with the separation of skin and mucous membranes at the dermal-epidermal junction. Although it is rare, many treatments have been trialed because of its high mortality rate. Active interventions performed to date include the use of systemic corticosteroids, intravenous immunoglobulins (IVIg), cyclosporine, plasmapheresis, anti-tumor necrosis factor drugs and N-acetylcysteine, but none has been established as the most effective therapy...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/28723802/tocilizumab-for-uncontrollable-systemic-inflammatory-response-syndrome-complicating-adult-onset-still-disease-case-report-and-review-of-literature
#15
Asami Masui-Ito, Ryuji Okamoto, Kaoru Ikejiri, Mika Fujimoto, Muneyoshi Tanimura, Shiro Nakamori, Tomohiro Murata, Eiji Ishikawa, Norikazu Yamada, Hiroshi Imai, Masaaki Ito
RATIONALE: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown etiology characterized by evanescent salmon-pink rash, fever spikes, arthralgia, and lymphadenopathy. AOSD usually has a good prognosis, but it can sometimes be fatal, especially when it is complicated by systemic inflammatory response syndrome (SIRS) and multiple organ failure. PATIENT CONCERNS: A previously healthy 26-year-old woman was referred to our hospital for persistent high fever and mild systemic edema...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28722255/drug-drug-interactions-between-triazole-antifungal-agents-used-to-treat-invasive-aspergillosis-and-immunosuppressants-metabolized-by-cytochrome-p450-3a4
#16
REVIEW
Andreas H Groll, Robert Townsend, Amit Desai, Nkechi Azie, Mark Jones, Marc Engelhardt, Anne-Hortense Schmitt-Hoffman, Robert J Brüggemann
Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first- or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus...
July 19, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28720540/formulations-and-toxicologic-in-vivo-studies-of-aqueous-cyclosporin-a-eye-drops-with-cyclodextrin-nanoparticles
#17
Sunna Jóhannsdóttir, Johannes K Kristinsson, Zoltán Fülöp, Gudrún Ásgrímsdóttir, Einar Stefánsson, Thorsteinn Loftsson
Cyclosporin A (CyA) is an immunosuppressive drug used topically to treat ocular inflammatory disorder such as dry eye disease (DES). It is a lipophilic cyclic peptide with molecular weight of 1202.6Da. The aim of this study was to develop surfactant free aqueous 0.2% (w/v) CyA eye drops where the drug is present in an aqueous vehicle containing CyA/cyclodextrin (CyA/CD) nanoparticles and then do three-month toxicological testing in rabbits. Five formulations of different CD concentrations were studied, all of them contained 12...
July 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28719256/therapeutic-dilemma-of-refractory-erythema-nodosum-leprosum
#18
Jianyu Zhu, Degang Yang, Chao Shi, Zhichun Jing
AbstractErythema nodosum leprosum (ENL), also known as type II leprosy reaction, is a severe immune-mediated complication of multibacillary leprosy. For ENL, corticosteroids and thalidomide are the mainstays of treatment. Other immunosuppressants, such as clofazimine, cyclosporine, and azathioprine have also been used. Although most patients with ENL respond well to conventional treatments, a small number are refractory to these therapies and have severe morbidity or mortality. We report the case of a 24-year-old man with refractory ENL treated with high-dose corticosteroids for 15 months...
June 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28716665/applying-label-free-dynamic-mass-redistribution-assay-for-studying-endogenous-fpr1-receptor-signalling-in-human-neutrophils
#19
Hanna B Christensen, David E Gloriam, Daniel Sejer Pedersen, Jack B Cowland, Niels Borregaard, Hans Bräuner-Osborne
INTRODUCTION: The label-free dynamic mass redistribution-based assay (DMR) is a powerful method for studying signalling pathways of G protein-coupled receptors (GPCRs). Herein we present the label-free DMR assay as a robust readout for pharmacological characterization of formyl peptide receptors (FPRs) in human neutrophils. METHODS: Neutrophils were isolated from fresh human blood and their responses to FPR1 and FPR2 agonists, i.e. compound 43, fMLF and WKYMVm were measured in a label-free DMR assay using Epic Benchtop System from Corning®...
July 14, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28714558/everolimus-and-reduced-calcineurin-inhibitor-therapy-in-pediatric-liver-transplant-recipients-results-from-a-multicenter-prospective-study
#20
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
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