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https://www.readbyqxmd.com/read/28107393/t-cell-subset-and-stimulation-strength-dependent-modulation-of-t-cell-activation-by-kv1-3-blockers
#1
Wai-Ping Fung-Leung, Wilson Edwards, Yi Liu, Karen Ngo, Julianty Angsana, Glenda Castro, Nancy Wu, Xuejun Liu, Ronald V Swanson, Alan D Wickenden
Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1...
2017: PloS One
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
#2
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/28104127/calcineurin-inhibitor-induced-pain-syndrome-in-abo-incompatible-living-kidney-transplantation-a-case-report
#3
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/28102966/histone-deacetylase-2-is-decreased-in-peripheral-blood-pro-inflammatory-cd8-t-and-nkt-like-lymphocytes-following-lung-transplant
#4
Greg Hodge, Sandra Hodge, Chien-Li Holmes-Liew, Paul N Reynolds, Mark Holmes
BACKGROUND AND OBJECTIVE: Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown...
February 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28102061/clinical-diversity-of-atopic-dermatitis-a-review-of-5-000-patients-at-a-single-institute
#5
Howard Chu, Jung U Shin, Chang Ook Park, Hemin Lee, Jungsoo Lee, Kwang Hoon Lee
PURPOSE: Atopic dermatitis (AD) is a chronic eczematous dermatitis that has a high prevalence and diverse clinical features. Although several hypotheses about its multifactorial pathogenesis have been suggested, the cause is not yet fully understood. A better understanding of the clinical features may helpful inelucidating the pathogenesis of AD. METHODS: This retrospective study analyzed the questionnaires, medical charts, and laboratory examination results of 5,000 patients diagnosed with AD at a single tertiary hospital in Korea...
March 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28101018/remarkable-improvement-of-nail-changes-in-alopecia-areata-universalis-with-10-months-of-treatment-with-tofacitinib-a-case-report
#6
Sineida Berbert Ferreira, Morton Scheinberg, Denise Steiner, Tatiana Steiner, Gustavo Longhi Bedin, Rachel Berbert Ferreira
Alopecia areata (AA) is a chronic, autoimmune disease. The main symptom is massive hair loss, localized or diffuse, in the scalp and the whole body. However, nails may also be involved, and brittleness, fragility and pitting can be signs of nail dystrophy in AA patients. Here, we report the case of a male patient with AA refractory to various treatments, including oral, topical and intralesional corticosteroids, immunosuppressants, cyclosporin and PUVA (oxoralen plus ultraviolet light), all interrupted due to side effects...
September 2016: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28100577/late-spontaneous-decapsulation-of-the-kidney-graft-in-a-patient-with-hepatitis-c-and-treated-with-sirolimus-possible-pathophysiological-association-in-a-rare-complication
#7
Rita Leal, Helena Pinto, Rui Alves, Arnaldo Figueiredo
Late decapsulation with fluid collection is a rare complication of renal transplantation with deleterious effects on kidney function. Its physiopathology is unclear but there might be an association with mammalian target of rapamycin (m-TOR) inhibitors, especially in patients with chronic hepatitis C. We report a case of late spontaneous decapsulation 12 years after kidney transplant in a patient infected with hepatitis C under treatment with sirolimus. He underwent marsupialisation of the collection, sirolimus was converted to cyclosporine and hepatitis C treatment was performed with success...
January 18, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28098122/a-case-of-abdominal-aortic-thrombosis-associated-with-the-nephrotic-syndrome
#8
Jannet Labidi, Yosra Selmi, Yosra Ben Ariba, Zied Elloumi, Saleh Othmani
Thromboembolic disease is an important and frequent complication in patients with the nephrotic syndrome (NS), and the consequences are often severe. Usually, the venous system is affected. Arterial thrombosis has rarely been reported and occurs mainly in children. We report the case of a 27-year-old man with a history of NS due to focal and segmental glomerulosclerosis resistant to steroids and cyclosporine, admitted for bilateral pain in the calves. Aortogram revealed a suspended thrombus in the abdominal aorta just below the origin of the renal arteries with embolism into the left tibioperoneal trunk and the right anterior tibial artery...
January 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28094770/rapamycin-mediated-mtor-inhibition-uncouples-hiv-1-latency-reversal-from-cytokine-associated-toxicity
#9
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/28093933/acute-kidney-injury-in-idiopathic-nephrotic-syndrome-of-childhood-is-a-major-risk-factor-for-the-development-of-chronic-kidney-disease
#10
Afshan Yaseen, Vina Tresa, Ali Asghar Lanewala, Seema Hashmi, Irshad Ali, Sabeeta Khatri, Muhammed Mubarak
BACKGROUND: Acute kidney injury (AKI) is an important complication of idiopathic nephrotic syndrome (INS) and is associated with adverse outcomes, especially the development of chronic kidney disease (CKD). We aimed to determine the clinical profile of children with INS who developed AKI and its short-term outcome. MATERIAL AND METHODS: This prospective study was conducted from March 2014 to October 2015. A total of 119 children of INS (age: 2-18 years) fulfilling the pediatric RIFLE criteria for the diagnosis of AKI were enrolled and followed up for 3 months to determine the outcome...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28093327/amorphous-solid-dispersion-of-cyclosporine-a-prepared-with-fine-droplet-drying-process-physicochemical-and-pharmacokinetic-characterization
#11
Hiroki Suzuki, Tatsuru Moritani, Tadahiko Morinaga, Yoshiki Seto, Hideyuki Sato, Satomi Onoue
The present study aimed to develop an amorphous solid dispersion (ASD) of cyclosporine A (CsA) by a fine droplet drying (FDD) process for improvement in oral absorption of CsA. CsA and hydroxypropyl cellulose-SSL were dissolved in 1,4-dioxane, and the solution was powdered by the FDD process to obtain the ASD formulation of CsA (ASD/CsA). The ASD/CsA was characterized in terms of morphology, particle size distribution, crystallinity, dissolution behavior, physicochemical stability, and pharmacokinetic behavior in rats...
January 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28091781/a-semifluorinated-alkane-f4h5-as-novel-carrier-for-cyclosporine-a-a-promising-therapeutic-and-prophylactic-option-for-topical-treatment-of-dry-eye
#12
Uta Gehlsen, Tobias Braun, Maria Notara, Sonja Krösser, Philipp Steven
PURPOSE: Cyclosporine A (Cs) has been used as effective topical therapy for inflammatory dry eye disease since more than a decade. However, due to its lipophilic character, Cs is formulated as emulsions or oily solutions for topical application. This experimental study aimed to test if the use of semifluorinated alkanes (SFAs) as a preservative-free, well-tolerated non-stinging or burning vehicle maintains or even improves the benefits of Cs in the topical therapy of dry-eye disease. METHODS: Desiccating stress was applied to C57BL/6 mice for 14 consecutive days to induce experimental dry-eye...
January 14, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28081041/a-systematic-literature-review-approach-to-estimate-the-therapeutic-index-of-selected-immunosuppressant-drugs-after-renal-transplantation
#13
Jessica E Ericson, Kanecia O Zimmerman, Daniel Gonzalez, Chiara Melloni, Jeffrey T Guptill, Kevin D Hill, Huali Wu, Michael Cohen-Wolkowiez
BACKGROUND: Drugs that exhibit close margins between therapeutic and toxic blood concentrations are considered to have a narrow therapeutic index (NTI). The Food and Drug Administration has proposed that NTI drugs should have more stringent bioequivalence standards for approval of generic formulations. However, many immunosuppressant drugs do not have a well-defined therapeutic index (TI). METHODS: We sought to determine whether safety, efficacy, and pharmacokinetic data obtained from the medical literature through a comprehensive literature search could be used to estimate the TI of cyclosporine, tacrolimus, and sirolimus...
February 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28079600/acute-administration-of-cyclosporine-a-does-not-impair-attention-or-memory-performance-in-healthy-men
#14
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/28070713/porous-mannitol-carrier-for-pulmonary-delivery-of-cyclosporine-a-nanoparticles
#15
Sharon Shui Yee Leung, Jennifer Wong, Heloisa Victorino Guerra, Kevin Samnick, Robert K Prud'homme, Hak-Kim Chan
This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carriers that incorporated hydrophobic cyclosporine A (CsA) nanoparticles (NPs) for pulmonary delivery. Two nanosuspension stabilization systems, (1) a combination of lecithin and lactose system and (2) a D-α-tocopheryl polyethylene glycol succinate (TPGS) system, were investigated. The ability of the lecithin and TPGS in anchoring the hydrophobic CsA NPs to the porous hydrophilic mannitol structure was first reported...
January 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28068383/inhibition-of-pterygium-fibroblast-migration-and-outgrowth-by-bevacizumab-and-cyclosporine-a-involves-down-regulation-of-matrix-metalloproteinases-3-and-13
#16
Yeoun-Hee Kim, Jae-Chang Jung, Sang Il Gum, Su-Bin Park, Jin Yeul Ma, Yong Il Kim, Kyoo Won Lee, Young Jeung Park
We examined the connection between matrix metalloproteinase (MMP) expression/activity and pterygium fibroblast migration, and how these were affected by bevacizumab and/or cyclosporine A (CsA). Fibroblasts were obtained from 20 pterygia and 6 normal conjunctival specimens. Expression levels of MMP-3 and MMP-13 were examined after bevacizumab administration. Immunofluorescence staining was used to examine expression of both MMPs in fibroblasts migrating out from explanted pterygium tissues. Rates of cell migration from explant-cultured pterygia tissues and scratch-wounded confluent pterygium fibroblasts were examined in the presence of MMP-3 or MMP-13 inhibitors, as well as bevacizumab and/or CsA...
2017: PloS One
https://www.readbyqxmd.com/read/28067873/cotransplantation-of-bone-marrow-derived-mesenchymal-stem-cells-in-haploidentical-hematopoietic-stem-cell-transplantation-in-patients-with-severe-aplastic-anemia-an-interim-summary-for-a-multicenter-phase-ii-trial-results
#17
Z Liu, Y Zhang, H Xiao, Z Yao, H Zhang, Q Liu, B Wu, D Nie, Y Li, Y Pang, Z Fan, L Li, Z Jiang, F Duan, H Li, P Zhang, Y Gao, L Ouyang, C Yue, M Xie, C Shi, Y Xiao, S Wang
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for severe aplastic anemia (SAA) is mainly limited by the high incidence of graft failure and GvHD. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis in vivo and to display potent immunosuppressive effects to prevent or treat GvHD after HSCT. In a multicenter phase II trial, we developed an approach with co-transplantation of MSCs in patients undergoing haplo-HSCT. Forty-four patients with SAA were included. The conditioning regimen included busulfan, cyclophosphamide and thymoglobulin (ATG)...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28063945/calcineurin-inhibitors-improve-memory-loss-and-neuropathological-changes-in-mouse-model-of-dementia
#18
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/28062700/intravital-imaging-of-neutrophil-recruitment-reveals-the-efficacy-of-fpr1-blockade-in-hepatic-ischemia-reperfusion-injury
#19
Masaki Honda, Takayuki Takeichi, Shintaro Hashimoto, Daiki Yoshii, Kaori Isono, Shintaro Hayashida, Yuki Ohya, Hidekazu Yamamoto, Yasuhiko Sugawara, Yukihiro Inomata
Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence is accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal that guides neutrophils to sites of inflammation. This study aimed to investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response to FPR1 blockade during hepatic I/R...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28062572/updates-in-understanding-the-role-of-cyclophilin-a-in-leukocyte-chemotaxis
#20
REVIEW
Farman Ullah Dawar, Junjie Wu, Lijuan Zhao, Muhammad Nasir Khan Khattak, Jie Mei, Li Lin
Cyclophilin A (CypA), a well-recognized receptor for anti-inflammatory drug cyclosporine A (CsA) is a ubiquitous and multifunctional protein. Beside the diverse intracellular functions, CypA is secreted against inflammatory stimuli, where it activates and attracts leukocytes via CD147 to the stimulus site. Interestingly, it synergizes with other factors to induce leukocyte migration in different animals. However, the silencing and inhibition of CypA or CD147 inhibits leukocytes chemotaxis and inflammation. This review focuses on the advances made in understanding the mechanism of CypA-dependent leukocytes chemotaxis and hence, recognition of this factor as a possible therapeutic target in inflammatory diseases...
January 6, 2017: Journal of Leukocyte Biology
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