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https://www.readbyqxmd.com/read/28644343/second-line-agents-in-pediatric-patients-with-autoimmune-hepatitis-a-systematic-review-and-meta-analysis
#1
Andréanne N Zizzo, Pamela L Valentino, Prakesh S Shah, Binita M Kamath
BACKGROUND AND AIMS: Ten percent to 20% of children with autoimmune hepatitis (AIH) require second-line therapy to achieve remission. Although current guidelines exist on first-line management, evidence for second-line therapy in treatment-refractory patients is lacking. Our aim was to perform a systematic review and meta-analysis of the efficacy and safety of second-line treatments used in this population. METHODS: Electronic and manual searches were used to identify potential studies for inclusion...
July 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28643580/cyclophilins-less-studied-proteins-with-critical-roles-in-pathogenesis
#2
Khushwant Singh, Mark Winter, Miloslav Zouhar, Pavel Rysanek
Cyclophilins (EC 5.2.1.8) (CYPs) belong to a subgroup of proteins known as immunophilins, which also include FK-506 binding proteins (FKBPs) and parvulins. Members of the immunophilins have two main characteristic properties: I) peptidyl-prolyl cis-trans isomerase activity (PPIases) and II) the ability to bind immunosuppressant molecules of fungal origin. Cyclophilins are some of the most conserved proteins present in eukaryotes and prokaryotes, and they have been implicated in diverse cellular processes and responses to multiple biotic and abiotic stresses...
June 23, 2017: Phytopathology
https://www.readbyqxmd.com/read/28640392/calcineurin-inhibitors-exacerbate-coronary-arteritis-via-the-myd88-signaling-pathway-in-a-murine-model-of-kawasaki-disease
#3
Kenji Murata, Yoshitomo Motomura, Tamami Tanaka, Shunsuke Kanno, Takahisa Yano, Mitsuho Onimaru, Atsushi Shimoyama, Hisanori Nishio, Yasunari Sakai, Masatsugu Oh-Hora, Hiromitsu Hara, Koichi Fukase, Hidetoshi Takada, Satohiro Masuda, Shouichi Ohga, Sho Yamasaki, Toshiro Hara
Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (Nod1) in wild-type, SCID, CARD9(-/-) , and MyD88(-/-) mice...
June 22, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28640015/the-effects-of-valsartan-on-renal-klotho-expression-and-oxidative-stress-in-alleviation-of-cyclosporine-nephrotoxicity-retraction
#4
(no author information available yet)
No abstract text is available yet for this article.
July 2017: Transplantation
https://www.readbyqxmd.com/read/28639977/topical-delivery-of-immunosuppression-to-prolong-xenogeneic-and-allogeneic-split-thickness-skin-graft-survival
#5
Melissa Mastroianni, Zhi Yang Ng, Ritu Goyal, Christopher Mallard, Evan A Farkash, David A Leonard, Alexander Albritton, Kumaran Shanmugarajah, Josef M Kurtz, David H Sachs, Lauren K Macri, Joachim Kohn, Curtis L Cetrulo
Cadaveric skin allograft is the current standard of treatment for temporary coverage of large burn wounds. Porcine xenografts are viable alternatives but undergo α-1,3-galactose (Gal)-mediated hyperacute rejection and are lost by POD 3 because of naturally occurring antibodies to Gal in primate recipients. Using baboons, we previously demonstrated that xenografts from GalT-KO swine (lacking Gal) provided wound coverage comparable with allografts with systemic immunosuppression. In this study, we investigate topical immunosuppression as an alternative to prolong xenograft survival...
June 7, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28635156/pyoderma-gangrenosum-and-underlying-diseases-in-japanese-patients-a-regional-long-term-study
#6
Sae Inoue, Jun-Ichi Furuta, Yasuhiro Fujisawa, Saori Onizawa, Shusaku Ito, Masayuki Sakiyama, Keiko Kobayashi, Toshiyuki Kanou, Shigeruko Iijima, Tsunao Ohi, Chimaki Okubo, Yoshihiro Moriyama, Naoko Okiyama, Manabu Fujimoto
Pyoderma gangrenosum (PG) is a chronic inflammatory disease of unknown cause that presents as an inflammatory and ulcerative disorder of the skin. PG is often associated with an underlying systemic disease. However, the frequencies of the underlying diseases are unclear in Japanese patients. In this retrospective, observational study, all patients diagnosed with PG who visited dermatology departments of nine regional hospitals in and around Ibaraki Prefecture were collected from 1982 to 2011 or 2014. The diagnoses of PG were based on the characteristic clinical and histological appearances and ruling out of infection...
June 21, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28634393/a-small-molecule-ds44170716-inhibits-ca-2-induced-mitochondrial-permeability-transition
#7
Naohiro Kon, Atsushi Satoh, Naoki Miyoshi
Mitochondria are involved in a variety of physiological and pathological processes. Ca(2+) uptake is one of the important functions of the organelle for maintenance of cellular Ca(2+) homeostasis. In pathological conditions such as ischemia reperfusion injury, Ca(2+) overload into mitochondria induces mitochondrial permeability transition (MPT), a critical step for cell death. Because inhibition of MPT is a promising approach to protecting cells and organs, it is important for drug discovery to identify novel chemicals or mechanisms to inhibit MPT...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633807/differential-induction-of-atf3-and-ho-1-in-myeloid-cells-and-keratinocytes-via-dimethylfumarate-or-cyclosporine-a
#8
Stefanie Müller, Nikola Smatlik, Marc Burian, Kamran Ghoreschi, Martin Röcken, Amir S Yazdi
BACKGROUND: Chronic inflammatory skin diseases are characterized by controlled proliferation of keratinocytes. Here, activating transcription factor 3 (ATF3) might play a fundamental role. In these inflammatory diseases, proliferation is controlled and only rarely leads to cancer development which can be supported by an inflammatory microenvironment. ATF3 is a dual function protein as it suppresses pro-inflammatory IL-6 and IL-8, but also acts as a pro-oncogenic factor by the suppression of p53...
June 12, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#9
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
June 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28630341/pig-model-mimicking-chronic-hepatitis-e-virus-infection-in-immunocompromised-patients-to-assess-immune-correlates-during-chronicity
#10
Dianjun Cao, Qian M Cao, Sakthivel Subramaniam, Danielle M Yugo, C Lynn Heffron, Adam J Rogers, Scott P Kenney, Debin Tian, Shannon R Matzinger, Christopher Overend, Nicholas Catanzaro, Tanya LeRoith, Heng Wang, Pablo Piñeyro, Nicole Lindstrom, Sherrie Clark-Deener, Lijuan Yuan, Xiang-Jin Meng
Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28629662/pyoderma-gangrenosum-classic-and-emerging-therapies
#11
REVIEW
Felipe Soto Vilches, Cristián Vera-Kellet
Pyoderma gangrenosum is an ulceronecrotising dermatosis that represents a challenge for any clinician, not only for its ability to mimic other dermatoses but also for its lack of response to treatment. During the past year, there have been new studies about the efficacy of standard therapies, such as cyclosporine and systemic corticosteroids. These studies showed that classic treatment was comparable, but they are insufficient as monotherapy. That being said, new emerging therapies are becoming important, as the use of corticosteroid-sparing agents, tumour necrosis factor inhibitors or even surgery...
June 16, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28628923/cremophor-el-alters-the-plasma-protein-binding-and-pharmacokinetic-profile-of-valspodar-in-rats
#12
Ziyad Binkhathlan
Cremophor EL is a nonionic surfactant widely used in pharmaceutical formulations. Nonetheless, there are several reports on the influence of this excipient on the protein binding, pharmacokinetics, and pharmacodynamics of drugs. Valspodar is an investigational non-immunosuppressive derivative of cyclosporine A, used in clinical trials for treatment of multidrug resistant tumors. The formulation of valspodar (Amdray(®)) contains cremophor EL and ethanol as solubilizing agents. The main aim of the current study was to assess the plasma protein binding (in vitro) and the pharmacokinetic profile of valspodar in the cremophor EL-based formulation in comparison to a cremophor EL-free formulation following intravenous (i...
June 19, 2017: Drug Research
https://www.readbyqxmd.com/read/28627456/effect-of-the-surface-layer-on-drug-release-from-delefilcon-a-dailies-total1-%C3%A2-contact-lenses
#13
Phillip Dixon, Anuj Chauhan
Contact lenses are receiving significant attention for delivering ophthalmic drugs with higher bioavailability compared to eye drops. Here we explore drug transport from delefilcon-A Dailies Total1(®) lenses which are designed to have a thin, high-water content layer on the surface. Our goal is to determine the impact of this high water content layer on drug transport for both hydrophobic (dexamethasone and cyclosporine) and hydrophilic (timolol and levofloxacin) drugs. Drugs were loaded into the lens by soaking in aqueous drug solutions till equilibrium, followed by release in phosphate buffered saline...
June 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28626181/long-term-low-density-lipoprotein-apheresis-in-a-patient-with-refractory-idiopathic-membranous-glomerulonephritis
#14
Junko Yabuuchi, Tatsuya Suwabe, Hiroki Mizuno, Toshiharu Ueno, Junichi Hoshino, Akinari Sekine, Masahiro Kawada, Masayuki Yamanouchi, Noriko Hayami, Rikako Hiramatsu, Eiko Hasegawa, Naoki Sawa, Kenmei Takaichi, Takeshi Fujii, Kenichi Ohashi, Yoshifumi Ubara
A 61-year-old Japanese man developed nephrotic syndrome (NS) due to idiopathic membranous glomerulonephritis (MGN). He received immunosuppressive therapy for two years, including prednisolone, cyclophosphamide, and cyclosporine A, but the NS persisted. Low-density lipoprotein apheresis (LDL-A) was initiated at a frequency of twice a month and continued for 9 years (203 sessions in total). His proteinuria reduced to less than 1 g daily after 9 years. LDL-A was stopped, and the NS has not relapsed for five years...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28625684/brand-medications-and-medicare-part-d-how-eye-care-providers-prescribing-patterns-influence-costs
#15
Paula Anne Newman-Casey, Maria A Woodward, Leslie M Niziol, Paul P Lee, Lindsey B De Lott
PURPOSE: To quantify costs of eye care providers' Medicare Part D prescribing patterns for ophthalmic medications and to estimate the potential savings of generic or therapeutic drug substitutions and price negotiation. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Eye care providers prescribing medications through Medicare Part D in 2013. METHODS: Medicare Part D 2013 prescriber public use file and summary file were used to calculate medication costs by physician specialty and drug...
June 16, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28624888/steady-state-pharmacokinetics-of-mycophenolic-acid-in-renal-transplant-patients-exploratory-analysis-of-the-effects-of-cyclosporine-recipients-and-donors-abcc2-gene-variants-and-their-interactions
#16
N Božina, Z Lalić, S Nađ-Škegro, A Borić-Bilušić, T Božina, Ž Kaštelan, V Trkulja
PURPOSE: The study aims to evaluate the impact of recipients' and donors' polymorphisms in multidrug resistance-associated protein 2 (MRP2) gene ABCC2 -24C>T and 1249G>A on disposition of mycophenolic acid (MPA) and their interaction with cyclosporine (CsA) (compared to tacrolimus, TAC) in stable de novo adult renal transplant patients of Croatian origin. METHODS: A total of 68 recipient-donor pairs were genotyped. Steady-state pharmacokinetics of MPA was assessed by the model-independent method...
June 18, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28624490/bioenergetics-dysfunction-mitochondrial-permeability-transition-pore-opening-and-lipid-peroxidation-induced-by-hydrogen-sulfide-as-relevant-pathomechanisms-underlying-the-neurological-dysfunction-characteristic-of-ethylmalonic-encephalopathy
#17
Gabriela Miranda Fernandez Cardoso, Julia Tauana Pletsch, Belisa Parmeggiani, Mateus Grings, Nícolas Manzke Glanzel, Larissa Daniele Bobermin, Alexandre Umpierrez Amaral, Moacir Wajner, Guilhian Leipnitz
Hydrogen sulfide (sulfide) accumulates at high levels in the brains of patients with ethylmalonic encephalopathy (EE). In the present study, we evaluated whether sulfide could disturb energy and redox homeostasis, and induce mitochondrial permeability transition (mPT) pore opening in rat brain aiming to better clarify the neuropathophysiology of EE. Sulfide decreased the activities of citrate synthase and aconitase in rat cerebral cortex mitochondria, and of creatine kinase (CK) in rat cerebral cortex, striatum and hippocampus supernatants...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28623616/cyclosporine-a-mediated-il-6-expression-promotes-neural-induction-in-pluripotent-stem-cells
#18
Ashwathnarayan Ashwini, Sushma S Naganur, Bhaskar Smitha, Preethi Sheshadri, Jyothi Prasanna, Anujith Kumar
Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28623111/reversal-of-abcb1-mediated-efflux-by-imatinib-and-nilotinib-in-cells-expressing-various-transporter-levels
#19
Petr Mlejnek, Petr Kosztyu, Petr Dolezel, Susan E Bates, Eliska Ruzickova
Recently, it has been suggested that imatinib (IM) and nilotinib (NIL) could be studied beyond their original application, as inhibitors of the drug efflux pump ABCB1 (P-glycoprotein, MDR1). Since the reversal of ABCB1-mediated resistance has never been successfully demonstrated in the clinic, we addressed the question of whether IM and NIL may actually serve as efficient inhibitors of ABCB1. Here we define an efficient inhibitor as a compound that achieves full (90-100%) reversal of drug efflux at a concentration that does not exhibit significant off-target toxicity in vitro...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28620753/population-pharmacokinetics-of-cyclosporine-a-in-japanese-renal-transplant-patients-comprehensive-analysis-in-a-single-center
#20
Akira Okada, Hidetaka Ushigome, Misaki Kanamori, Aya Morikochi, Hidefumi Kasai, Tadashi Kosaka, Takatoshi Kokuhu, Asako Nishimura, Nobuhito Shibata, Keizo Fukushima, Norio Yoshimura, Nobuyuki Sugioka
PURPOSE: Cyclosporine A (CyA), a potent immunosuppressive agent used in renal transplantation, has a narrow therapeutic window and a large variability in blood concentrations. This study aimed to develop a population pharmacokinetic (PPK) model of CyA in living-donor renal transplant patients at a single center and identify factors influencing CyA pharmacokinetics (PK). METHODS: A total of 660 points (preoperative) and 4785 points (postoperative) of blood concentration data from 98 patients who underwent renal transplantation were used...
June 15, 2017: European Journal of Clinical Pharmacology
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