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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28059474/csa-promotes-xist-expression-to-regulate-human-trophoblast-cells-proliferation-and-invasion-through-mir-144-titin-axis
#10
Nanhui Yu, Ying Liang, Hong Zhu, Hongying Mo, Haiping Pei
In our previous study, we revealed that Cyclosporin A (CsA) could inhibit miR-144 expression to regulate proliferation and invasion of human trophoblast (HT) cells through miR-144 targeting titin. This partially demonstrated the mechanism by which CsA promotes titin expression to increase the vitality of HT cells. However, the mechanism by which CsA inhibits miR-144 expression remains to be investigated. Recently, the interaction between lncRNA and miRNA has been frequently reported to play major role in several biological processes...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28058540/juvenile-dermatomyositis-a-tertiary-center-experience
#11
Kenan Barut, Pinar Ozge Avar Aydin, Amra Adrovic, Sezgin Sahin, Ozgur Kasapcopur
Juvenile dermatomyositis (JDM) is a rare chronic inflammatory disease of unknown etiology and primarily involves muscle and skin. It is the most common idiopathic inflammatory myopathy of childhood. This study aimed to evaluate demographic and clinical features, laboratory data, treatment modalities, and outcome of patients with JDM at a referral pediatric rheumatology center in Turkey. We retrospectively reviewed medical records of patients diagnosed with JDM between the years 2003-2016 at the Pediatric Rheumatology Department Cerrahpasa Medical Faculty...
January 5, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28058220/tacrolimus-confers-lower-acute-rejection-rates-and-better-renal-allograft-survival-compared-to-cyclosporine
#12
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/28057718/calcium-mediated-oxidative-stress-a-common-mechanism-in-tight-junction-disruption-by-different-types-of-cellular-stress
#13
Ruchika Gangwar, Avtar Meena, Pradeep Shukla, Archana Nagaraja, Piotr Dorniak, Sandeep Pallikuth, Christopher Waters, Anil Sood, Radhakrishna Rao
The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction disruption was investigated in Caco-2 cell monolayers in vitro , and restraint stress-induced barrier dysfunction in mouse colon in vivo Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca(2+) by BAPTA. Knockdown of CaV1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated tight junction disruption and barrier dysfunction...
January 5, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28057509/promoting-bioengineered-tooth-innervation-using-nanostructured-and-hybrid-scaffolds
#14
S Kuchler-Bopp, A Larrea, L Petry, Y Idoux-Gillet, V Sebastian, A Ferrandon, P Schwinté, M Arruebo, N Benkirane-Jessel
: The innervation of teeth mediated by axons originating from the trigeminal ganglia is essential for their function and protection. Immunosuppressive therapy using Cyclosporine A (CsA) was found to accelerate the innervation of transplanted tissues and particularly that of bioengineered teeth. To avoid the CsA side effects, we report in this study the preparation of CsA loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles, their embedding on polycaprolactone (PCL)-based scaffolds and their possible use as templates for the innervation of bioengineered teeth...
January 2, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28054752/opposite-modulatory-effects-of-selective-and-non-selective-cyclooxygenase-inhibition-on-cardiovascular-and-autonomic-consequences-of-cyclosporine-in-female-rats
#15
Karim S Ibrahim, Ahmed F El-Yazbi, Hanan M El-Gowelli, Mahmoud M El-Mas
Non-steroidal anti-inflammatory drugs (NSAIDs) and the immunosuppressant drug cyclosporine (CSA) are concurrently administered in arthritis. Here, we investigated whether diclofenac (non-selective inhibitor of cyclooxygenase-1 and 2, COX-1/COX-2), celecoxib (selective COX-2 inhibitor) or SC560 (selective COX-1 inhibitor) interact variably with hemodynamic effects of CSA in conscious female rats. Changes caused by CSA (10 mg/kg i.v.) in blood pressure (BP), heart rate (HR), HR variability (HRV) and myocardial contractility were assessed in absence and presence of individual NSAIDs (10 mg/kg each)...
January 5, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28053696/invasive-thymoma-with-pure-red-cell-aplasia-and-amegakaryocytic-thrombocytopenia
#16
Takuya Onuki, Yusuke Kiyoki, Sho Ueda, Masatoshi Yamaoka, Seiich Shimizu, Masaharu Inagaki
We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL), thrombocytopenia (platelet count, 0.6 × 10(4)/μL), and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT)...
November 2, 2016: Hematology Reports
https://www.readbyqxmd.com/read/28052467/the-combination-of-cyclosporine-and-mycophenolate-mofetil-is-less-effective-than-cyclosporine-and-methotrexate-in-the-prevention-of-acute-graft-versus-host-disease-after-stem-cell-transplantation-from-unrelated-donors
#17
Ronit Yerushalmi, Noga Shem-Tov, Ivetta Danylesko, Roni Shouval, Arnon Nagler, Avichai Shimoni
Acute graft-versus-host disease (GVHD) is the major treatment-related complication after stem-cell transplantation (SCT) from unrelated-donors. Several GVHD prophylaxis regimens have been explored, but no regimen has shown superiority. We analyzed transplantation outcomes in 472 consecutive unrelated-donor SCT recipients, using cyclosporine/methotrexate (MTX, n=314) or cyclosporine/mycophenolate-mofetil (MMF, n=158) for GVHD prophylaxis. Neutrophil engraftment was faster after MMF, day 11 and 14, respectively (P=0...
January 4, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28051798/%C3%A2-conversion-to-mycophenolate-mofetil-monotherapy-in-liver-recipients-calcineurin-inhibitor-levels-are-key
#18
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/28045880/targeted-complement-inhibition-protects-vascularized-composite-allografts-from-acute-graft-injury-and-prolongs-graft-survival-when-combined-with-subtherapeutic-cyclosporine-a-therapy
#19
Peng Zhu, Stefanie R Bailey, Biao Lei, Chrystal M Paulos, Carl Atkinson, Stephen Tomlinson
BACKGROUND: Recipients of vascularized composite allografts require aggressive and life-long immunosuppression, and since the surgery is usually performed in nonlife threatening situations, the development of strategies to minimize immunosuppression is especially pertinent for this procedure. We investigated how complement affects acute graft injury, alloimmunity, and immunosuppressive therapy. METHODS: Vascularized composite allografts were transplanted from Balb/C to C57BL/6 mice that were complement deficient (C3 or double C3a Receptor (R)/C5aR), or treated with a targeted complement inhibitor (CR2-Crry)...
December 30, 2016: Transplantation
https://www.readbyqxmd.com/read/28042353/immunosuppressive-therapy-after-solid-organ-transplantation-does-the-intermed-identify-patients-at-risk-of-poor-adherence
#20
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
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