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https://www.readbyqxmd.com/read/28914229/clinical-effectiveness-and-cost-effectiveness-of-beta-interferon-and-glatiramer-acetate-for-treating-multiple-sclerosis-systematic-review-and-economic-evaluation
#1
G J Melendez-Torres, Peter Auguste, Xavier Armoiry, Hendramoorthy Maheswaran, Rachel Court, Jason Madan, Alan Kan, Stephanie Lin, Carl Counsell, Jacoby Patterson, Jeremy Rodrigues, Olga Ciccarelli, Hannah Fraser, Aileen Clarke
BACKGROUND: At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. OBJECTIVES: To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other...
September 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28901194/acute-renal-graft-versus-host-disease-in-a-murine-model-of-allogeneic-bone-marrow-transplantation
#2
Peter M Schmid, Abdellatif Bouazzaoui, Karin Schmid, Christoph Birner, Christian Schach, Lars S Maier, Ernst Holler, Dierk H Endemann
Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and is associated with a poor prognosis. Generally, the kidneys are assumed to not be no direct targets of graft-versus-host disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully major histocompatibility complex (MHC)-mismatched model of BALB/c mice conditioned and transplanted according to 2 different intensity protocols...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28895584/effects-of-lobeglitazone-a-novel-thiazolidinedione-on-adipose-tissue-remodeling-and-brown-and-beige-adipose-tissue-development-in-db-db-mice
#3
G Kim, Y-H Lee, M R Yun, J-Y Lee, E G Shin, B-W Lee, E S Kang, B-S Cha
BACKGROUND/OBJECTIVES: We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of PPARγ, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice. METHODS: Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg/kg daily) was injected intraperitoneally for 20 weeks. RESULTS: Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity, and preserved pancreatic beta cells...
September 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28883123/post-translational-modification-of-the-interferon-gamma-receptor-alters-its-stability-and-signaling
#4
James D Londino, Dexter L Gullick, Travis B Lear, Tomeka L Suber, Nathaniel M Weathington, Luke S Masa, Bill B Chen, Rama K Mallampalli
The IFN gamma receptor 1 (IFNGR1) binds IFN gamma and activates gene transcription pathways crucial for controlling bacterial and viral infections. Although decreases in IFNGR1 surface levels have been demonstrated to inhibit IFN gamma signaling, little is known regarding the molecular mechanisms controlling receptor stability. Here we show in epithelial and monocytic cell lines that IFNGR1 displays K48 polyubiquitination, is proteasomally degraded, and harbors three ubiquitin acceptor sites at K277, K279, and K285...
September 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28877912/type-1-interferons-potentiate-human-cd8-t-cell-cytotoxicity-through-a-stat4-and-granzyme-b-dependent-pathway
#5
Brittney N Newby, Todd M Brusko, Baiming Zou, Mark A Atkinson, Michael Clare-Salzler, Clayton E Mathews
Events defining the progression to human type 1 diabetes (T1D) have remained elusive owing to the complex interaction between genetics, the immune system, and the environment. Type 1 Interferons (T1-IFN) are known to be a constituent of the auto-inflammatory milieu within the pancreas of patients with T1D. However, the capacity of IFNα/β to modulate human activated auto-reactive CD8(+) T cell (CTL) responses within the islets of patients with T1D have not been investigated. Here, we engineer human beta cell specific CTLs and demonstrate that T1-IFN augments cytotoxicity by inducing rapid phosphorylation of STAT4, resulting in direct binding at the granzyme B (GZMB) promoter within 2 hours of exposure...
September 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28840599/butyltin-compounds-alter-secretion-of-interleukin-6-from-human-immune-cells
#6
Shyretha Brown, Wendy Wilburn, Tyesha Martin, Margaret Whalen
Butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT) are organotin compounds that have been used in a variety of industrial applications; as a result, these compounds have been found in human blood. Interleukin (IL)-6 is a proinflammatory mediator that is produced by T lymphocytes and monocytes. It is responsible for immune response regulation as well as tissue repair and cellular growth. Both BTs decrease the ability of human natural killer cells to destroy tumor cells and alter the secretion of proinflammatory cytokines tumor necrosis factor alpha, interferon gamma and IL-1 beta (β) from human lymphocytes ex vivo...
August 24, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28819935/plasma-biomarkers-of-inflammation-reflect-seizures-and-hemorrhagic-activity-of-cerebral-cavernous-malformations
#7
Romuald Girard, Hussein A Zeineddine, Maged D Fam, Anoop Mayampurath, Ying Cao, Changbin Shi, Robert Shenkar, Sean P Polster, Michael Jesselson, Ryan Duggan, Abdul-Ghani Mikati, Gregory Christoforidis, Jorge Andrade, Kevin J Whitehead, Dean Y Li, Issam A Awad
The clinical course of cerebral cavernous malformations (CCMs) is highly variable. Based on recent discoveries implicating angiogenic and inflammatory mechanisms, we hypothesized that serum biomarkers might reflect chronic or acute disease activity. This single-site prospective observational cohort study included 85 CCM patients, in whom 24 a priori chosen plasma biomarkers were quantified and analyzed in relation to established clinical and imaging parameters of disease categorization and severity. We subsequently validated the positive correlations in longitudinal follow-up of 49 subjects...
August 17, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28815942/plasma-membrane-protein-profiling-in-beta-amyloid-treated-microglia-cell-line
#8
Virginia Correani, Laura Di Francesco, Giuseppina Mignogna, Cinzia Fabrizi, Stefano Leone, Alessandra Giorgi, Alessia Passeri, Roberto Casata, Lorenzo Fumagalli, Bruno Maras, M Eugenia Schininà
In the responsiveness of microglia to toxic stimuli, plasma membrane proteins play a key role. In this study we treated with a synthetic beta amyloid peptide murine microglial cells metabolically differently labelled with stable isotope amino acids (SILAC). The plasma membrane was selectively enriched by a multi-stage aqueous two-phase partition system. We were able to identify by 1D-LC-MS/MS analyses 1577 proteins, most of them are plasma membrane proteins according to the Gene Ontology annotation. An unchanged level of amyloid receptors in this data set, suggests that microglia preserve their responsiveness capability to the environment even after 24 h-challenge with amyloid peptides...
August 16, 2017: Proteomics
https://www.readbyqxmd.com/read/28797847/cytokine-gene-polymorphisms-associated-with-symptom-clusters-in-oncology-patients-undergoing-radiation-therapy
#9
Christine Miaskowski, Yvette P Conley, Judy Mastick, Steven M Paul, Bruce A Cooper, Jon D Levine, Mitchell Knisely, Kord M Kober
CONTEXT: Most of the reviews on the biological basis for symptom clusters suggest that inflammatory processes are involved in the development and maintenance of the symptom clusters. However, no studies have evaluated for associations between genetic polymorphisms and common symptom clusters (e.g., mood disturbance, sickness behavior). OBJECTIVES: Examine the associations between cytokine gene polymorphisms and the severity of three distinct symptom clusters (i...
August 7, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28791286/autoimmune-thrombotic-thrombocytopenic-purpura-two-rare-cases-associated-with-juvenile-idiopathic-arthritis-and-multiple-sclerosis
#10
Despoina Dimopoulou, Athina Dimosiari, Eudokia Mandala, Theodoros Dimitroulas, Alaxandros Garyfallos
Secondary thrombotic microangiopathies are associated with several underlying conditions, with most of them being resolved after the treatment of background disease. Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathy presenting with anemia, thrombocytopenia, and neurological deficits, occurring most often in various autoimmune diseases due to inhibition of ADAMTS13 by autoantibodies, as well as in pregnant women with or without an autoimmune substrate. In this article, we report two newly diagnosed TTP cases, who have not been published so far...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28791126/investigation-of-sphingosine-kinase-1-in-interferon-responses-during-dengue-virus-infection
#11
Amanda L Aloia, Julie K Calvert, Jennifer N Clarke, Lorena T Davies, Karla J Helbig, Stuart M Pitson, Jillian M Carr
Dengue virus (DENV) regulates sphingosine kinase (SK)-1 activity and chemical inhibition of SK1 reduces DENV infection. In primary murine embryonic fibroblasts (pMEFs) lacking SK1 however, DENV infection is enhanced and this is associated with induction of normal levels of interferon beta (IFN-β) but reduced levels of IFN-stimulated genes (ISGs). We have further investigated this link between SK1 and type I IFN responses. DENV infection downregulates cell-surface IFN-alpha receptor (IFNAR)1 in both wild-type (WT) and SK1(-)(/-) pMEF, but, consistent with poor ISG responses, shows reduced induction of phosphorylated (p)-STAT1 and key IFN regulatory factors (IRF)1 and -7 in SK1(-/-) pMEF...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28751099/efficacy-and-safety-of-delayed-release-dimethyl-fumarate-for-relapsing-remitting-multiple-sclerosis-in-prior-interferon-users-an-integrated-analysis-of-define-and-confirm
#12
Óscar Fernández, Gavin Giovannoni, Robert J Fox, Ralf Gold, J Theodore Phillips, James Potts, Macaulay Okwuokenye, Jing L Marantz
PURPOSE: In Phase III studies (DEFINE [Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS]/CONFIRM [Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis]), delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Post hoc analyses of integrated data from DEFINE/CONFIRM were conducted to evaluate the effect of DMF in patients previously treated with interferon (IFN) beta...
July 24, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28747868/protective-effect-of-momordica-charantia-water-extract-against-liver-injury-in-restraint-stressed-mice-and-the-underlying-mechanism
#13
Yuanyuan Deng, Qin Tang, Yan Zhang, Ruifen Zhang, Zhencheng Wei, Xiaojun Tang, Mingwei Zhang
Background: Momordica charantia is used in China for its jianghuo (heat-clearing and detoxifying) effects. The concept of shanghuo (the antonym of jianghuo, excessive internal heat) in traditional Chinese medicine is considered a type of stress response of the body. The stress process involves internal organs, especially the liver. Objective: We hypothesized that Momordica charantia water extract (MWE) has a hepatoprotective effect and can protect the body from stress. The aim of this study was to investigate the possible effects of MWE against liver injury in restraint-stressed mice...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28726530/incremental-net-monetary-benefit-of-ocrelizumab-relative-to-subcutaneous-interferon-%C3%AE-1a
#14
Melissa A Frasco, Tiffany Shih, Devin Incerti, Oliver Diaz Espinosa, Diana K Vania, Nina Thomas
AIM: Disease-modifying therapies (DMTs) impact the natural history of relapsing forms of multiple sclerosis (RRMS) by reducing annual relapse rates and slowing disability progression. The effect of DMTs on indirect costs has not been consistently explored in cost-effectiveness studies thus far. The value to patients of an emerging DMT, ocrelizumab, was quantified in comparison to subcutaneous interferon beta-1a (IFNβSC) for the prevalent RRMS population with mild-to-moderate disability in the US, based on two Phase 3 trials, OPERA I and OPERA II, of ocrelizumab vs IFNβSC in RRMS...
August 4, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28721023/persistence-to-disease-modifying-therapies-for-multiple-sclerosis-in-a-canadian-cohort
#15
Dessalegn Y Melesse, Ruth Ann Marrie, James F Blanchard, Bo Nancy Yu, Charity Evans
PURPOSE: To examine the long-term persistence to the first-line injectable disease-modifying therapies (DMTs) for multiple sclerosis (MS) and to identify the factors associated with nonpersistence. PATIENTS AND METHODS: We used population-based administrative data from Manitoba, Canada. All adult subjects who were diagnosed with MS and dispensed a first-line injectable DMT (beta-interferon-1b, beta-interferon-1a, and glatiramer acetate) between 1996 and 2011 and had a minimum of 1 year of follow-up were included...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28717427/comparison-of-the-effects-of-low-dose-interferon-and-high-dose-interferon-on-reduction-of-the-number-and-size-of-plaques-in-patients-with-multiple-sclerosis-a-historical-cohort
#16
Payam Khomand, Ghobad Moradi, Behrooz Ahsan, Setareh Abtahi
Background: This study was performed to compare the effects of low dose interferon beta-1 (IFN-β-1) (CinnoVex, 30 mcg) and high dose IFN-β-1 (REBIF, 44 mcg) on the reduction of the number and size of plaques in magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS). Methods: This historical cohort study, which was performed in 2014 in Sanandaj (western part of Iran). 43 MS patients in two groups were investigated. The first group, which included 19 patients, was treated using high dose IFN (44 mcg) and the second group, which was consisted of 24 patients, was treated using low dose IFN (30 mcg)...
January 5, 2017: Iranian Journal of Neurology
https://www.readbyqxmd.com/read/28691653/molecular-biochemical-characterization-and-assessment-of-immunogenic-potential-of-cofactor-independent-phosphoglycerate-mutase-against-leishmania-donovani-a-step-towards-exploring-novel-vaccine-candidate
#17
Rati Tandon, Sharat Chandra, Rajendra Kumar Baharia, Pragya Misra, Sanchita DAS, Keerti Rawat, Mohammad Imran Siddiqi, Shyam Sundar, Anuradha Dube
Despite immense efforts, vaccine against visceral leishmaniasis has yet not been developed. Earlier our proteomic study revealed a novel protein, cofactor-independent phoshoglycerate mutase (LdiPGAM), an important enzyme in glucose metabolism, in T helper cells type 1 (Th1) stimulatory region of soluble Leishmania donovani antigen. In this study, LdiPGAM was biochemically and molecularly characterized and evaluated for its immunogenicity and prophylactic efficacy against L. donovani. Immunogenicity of recombinant LdiPGAM (rLdiPGAM) was initially assessed in naïve hamsters immunized with it by analysing mRNA expression of inducible nitric oxide (NO) synthase (iNOS) and other Th1/T helper cells type 2 cytokines, which revealed an upregulation of Th1 cytokines along with iNOS...
July 10, 2017: Parasitology
https://www.readbyqxmd.com/read/28689166/ocular-surface-cytokine-profile-in-chronic-stevens-johnson-syndrome-and-its-response-to-mucous-membrane-grafting-for-lid-margin-keratinisation
#18
Srividya Gurumurthy, Geetha Iyer, Bhaskar Srinivasan, Shweta Agarwal, Narayanasamy Angayarkanni
BACKGROUND: To study the tear cytokine and the conjunctival and oral mucosal marker profile in chronic ocular Stevens-Johnson syndrome (SJS) and their alteration following mucous membrane grafting (MMG) for lid margin keratinisation (LMK). METHODS: In a 1-year prospective study, SJS cases (n=25) and age-matched/sex-matched healthy controls (n=25) were recruited. Tear specimen (Schirmer's strip), conjunctival and oral mucosal imprints were collected from controls and SJS cases pre-MMG and post-MMG (at first follow-up, n=17)...
July 8, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28689102/monthly-methylprednisolone-in-combination-with-interferon-beta-or-glatiramer-acetate-for-relapsing-remitting-multiple-sclerosis-a-multicentre-single-blind-prospective-trial
#19
Serkan Ozakbas, Bilge Piri Cinar, Gorkem Kosehasanoğullari, Turhan Kahraman, Didem Oz, Behice Bircan Kursun
OBJECTIVES: Multiple sclerosis is usually clinically characterized by repeated subacute relapses followed by remissions. Corticosteroids are used for relapses, and this treatment has been shown to increase the speed of recovery from these. We aimed to evaluate the efficacy and safety of pulsed methylprednisolone given every month as an add-on therapy to interferon beta or glatiramer acetate in patients with relapsing-remitting multiple sclerosis. PATIENTS AND METHODS: This was a multi-center, examiner-blinded, prospective study...
September 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28686675/management-of-flu-like-syndrome-with-cetirizine-in-patients-with-relapsing-remitting-multiple-sclerosis-during-therapy-with-interferon-beta-results-of-a-randomized-cross-over-placebo-controlled-pilot-study
#20
Doriana Landi, Maria Albanese, Fabio Buttari, Fabrizia Monteleone, Laura Boffa, Silvia Rossi, Caterina Motta, Elisa Puma, Diego Centonze
BACKGROUND: Flu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS. METHODS: We conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ...
2017: PloS One
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