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https://www.readbyqxmd.com/read/28328761/drug-efficacy-monitoring-in-pharmacotherapy-of-multiple-sclerosis-with-biological-agents
#1
M Caldano, W Raoul, T Rispens, A Bertolotto
Multiple Sclerosis (MS) is a heterogeneous disease. Although several EMA approved Disease Modifying Treatments including biopharmaceuticals are available, their efficacy is limited and a certain percentage of patients are always non-responsive. Drug Efficacy Monitoring is an important tool to identify these non-responsive patients early on. Currently, Detection of Anti-Drug Antibodies and quantification of Biological Activity are used as methods of efficacy monitoring for Interferon beta (IFNβ) and Natalizumab (NAT) therapies...
March 22, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28328217/development-of-a-selective-inhibitor-of-protein-arginine-deiminase-2
#2
Aaron Muth, Venkataraman Subramanian, Edward Beaumont, Mitesh Nagar, Philip Kerry, Paul McEwan, Hema Srinath, Kathleen Wanda Clancy, Sangram S Parelkar, Paul R Thompson
Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated. To achieve this goal, we synthesized a series of benzimidazole-based derivatives of Cl-amidine, hypothesizing that this scaffold would allow access to a series of PAD2-selective inhibitors with enhanced cellular efficacy...
March 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28328179/effect-of-delayed-release-dimethyl-fumarate-on-no-evidence-of-disease-activity-in-relapsing-remitting-multiple-sclerosis-integrated-analysis-of-the-phase-iii-define-and-confirm-studies
#3
E Havrdova, G Giovannoni, R Gold, R J Fox, L Kappos, J Theodore Phillips, M Okwuokenye, J L Marantz
BACKGROUND AND PURPOSE: Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing-remitting multiple sclerosis. METHODS: The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years...
March 22, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28327637/erratum-antibodies-from-multiple-sclerosis-patients-preferentially-recognize-hyperglucosylated-adhesin-of-non-typeable-haemophilus-influenzae
#4
Marthe T C Walvoort, Chiara Testa, Raya Eilam, Rina Aharoni, Francesca Nuti, Giada Rossi, Feliciana Real-Fernandez, Roberta Lanzillo, Vincenzo Brescia Morra, Francesco Lolli, Paolo Rovero, Barbara Imperiali, Anna Maria Papini
No abstract text is available yet for this article.
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327523/methodological-challenges-in-protein-microarray-and-immunohistochemistry-for-the-discovery-of-novel-autoantibodies-in-paediatric-acute-disseminated-encephalomyelitis
#5
Patrick Peschl, Melanie Ramberger, Romana Höftberger, Karin Jöhrer, Matthias Baumann, Kevin Rostásy, Markus Reindl
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients...
March 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28327374/discovery-and-molecular-interaction-studies-of-a-highly-stable-tarantula-peptide-modulator-of-acid-sensing-ion-channel-1
#6
REVIEW
Sing Yan Er, Ben Cristofori-Armstrong, Pierre Escoubas, Lachlan D Rash
Acute pharmacological inhibition of acid-sensing ion channel 1a (ASIC1a) is efficacious in rodent models in alleviating symptoms of neurological diseases such as stroke and multiple sclerosis. Thus, ASIC1a is a promising therapeutic target and selective ligands that modulate it are invaluable research tools and potential therapeutic leads. Spider venoms have provided an abundance of voltage-gated ion channel modulators, however, only one ASIC modulator (PcTx1) has so far been isolated from this source. Here we report the discovery, characterization, and chemical stability of a second spider venom peptide that potently modulates ASIC1a and ASIC1b, and investigate the molecular basis for its subtype selectivity...
March 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28327329/ocrelizumab-in-multiple-sclerosis-markers-and-mechanisms
#7
Reinhard Hohlfeld, Edgar Meinl
No abstract text is available yet for this article.
April 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28327094/finger-tapping-impairments-are-highly-sensitive-for-evaluating-upper-motor-neuron-lesions
#8
Afsaneh Shirani, Braeden D Newton, Darin T Okuda
BACKGROUND: Identifying highly sensitive and reliable neurological exam components are crucial in recognizing clinical deficiencies. This study aimed to investigate finger tapping performance differences between patients with CNS demyelinating lesions and healthy control subjects. METHODS: Twenty-three patients with multiple sclerosis or clinically isolated syndrome with infratentorial and/or cervical cord lesions on MRI, and 12 healthy controls were videotaped while tapping the tip of the index finger against the tip and distal crease of the thumb using both the dominant and non-dominant hand...
March 21, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28327056/multiple-sclerosis-and-suicide
#9
Anthony Feinstein, Bennis Pavisian
Mortality rates are elevated in people with multiple sclerosis (MS) relative to the general population. There is, however, some uncertainty whether suicide contributes to this. Epidemiological data suggest that the standardized mortality ratio (SMR) for suicide in MS is approximately twice that of the general population with younger males in the first few years following diagnosis most at risk. Rates of suicidal intent, a potential harbinger of more self-destructive behavior, are also elevated, but the frequency with which intent is followed by suicide is not known...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28326637/purinergic-receptors-p2rx4-and-p2rx7-in-familial-multiple-sclerosis
#10
A Dessa Sadovnick, Ben J Gu, Anthony L Traboulsee, Cecily Q Bernales, Mary Encarnacion, Irene M Yee, Maria G Criscuoli, Xin Huang, Amber Ou, Carol J Milligan, Steven Petrou, James S Wiley, Carles Vilariño-Güell
Genetic variants in the purinergic receptors P2RX4 and P2RX7 have been shown to affect susceptibility to multiple sclerosis (MS). In this study we set out to evaluate whether rare coding variants of major effect could also be identified in these purinergic receptors. Sequencing analysis of P2RX4 and P2RX7 in 193 MS patients and 100 controls led to the identification of a rare three variant haplotype (P2RX7 rs140915863:C>T (p.T205M), P2RX7 rs201921967:A>G (p.N361S) and P2RX4 rs765866317:G>A (p.G135S)) segregating with disease in a multi-incident family with six family members diagnosed with MS (LOD = 3...
March 21, 2017: Human Mutation
https://www.readbyqxmd.com/read/28326412/total-knee-arthroplasty-in-multiple-sclerosis
#11
Kaitlyn E Hughes, Darren Nickel, Tanner Gurney-Dunlop, Katherine B Knox
We present a case report of total knee arthroplasty complicated by spasticity and contractures in a patient with multiple sclerosis (MS). Four previous case reports in the literature describe adverse outcomes after total knee arthroplasty in persons with MS secondary to severe spasticity. Preoperative, intraoperative, and postoperative considerations for persons with MS, which may help to improve functional outcomes, are discussed. Prospective research is needed among persons with MS to help determine the timing and selection of persons for arthroplasty and to minimize complications related to spasticity...
September 2016: Arthroplasty Today
https://www.readbyqxmd.com/read/28326328/cooccurrences-of-putative-endogenous-retrovirus-associated-diseases
#12
REVIEW
Christine Brütting, Alexander Emmer, Malte E Kornhuber, Martin S Staege
At least 8% of the human genome is composed of endogenous retrovirus (ERV) sequences. ERVs play a role in placental morphogenesis and can sometimes protect the host against exogenous viruses. On the other hand, ERV reactivation has been found to be associated with different diseases, for example, multiple sclerosis (MS), schizophrenia, type 1 diabetes mellitus (T1D), or amyotrophic lateral sclerosis (ALS). Little is known about the cooccurrence of these diseases. If all these diseases are caused by ERV, antiretroviral therapy should perhaps also show some effects in the other diseases...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28325251/interferon-induced-thrombotic-microangiopathy-tma-analysis-and-concise-review
#13
REVIEW
Ajay Kundra, Jen Chin Wang
Interferon (IFN) has been associated with development of thrombotic microangiopathy including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We reviewed literature from the earliest reported association in 1993, to July 2016 and found 68 cases. Analysis of this data shows: (1) Mean age at diagnosis was 47 years (95% CI, 44-50). (2) Majority of cases were seen where IFN was used for the treatment of chronic myelogenous leukemia (CML), multiple sclerosis (MS), chronic hepatitis C virus infection (HCV) and one case each for hairy cell leukemia (HCL) and Sezary syndrome...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28325094/validity-and-reliability-of-the-multidimensional-assessment-of-fatigue-scale-in-iranian-patients-with-relapsing-remitting-subtype-of-multiple-sclerosis
#14
Shabnam Behrangrad, Amin Kordi Yoosefinejad
PURPOSE: The purpose of this study is to investigate the validity and reliability of the Persian version of the Multidimensional Assessment of Fatigue Scale (MAFS) in an Iranian population with multiple sclerosis. METHOD: A self-reported survey on fatigue including the MAFS, Fatigue Impact Scale and demographic measures was completed by 130 patients with multiple sclerosis and 60 healthy persons sampled with a convenience method. Test-retest reliability and validity were evaluated 3 days apart...
March 21, 2017: Disability and Rehabilitation
https://www.readbyqxmd.com/read/28324879/quantitative-analysis-of-uveitis-macular-edema-in-multiple-sclerosis-patients-receiving-deep-posterior-sub-tenon-triamcinolone-acetonide-injection
#15
Svetlana Jovanović, Tatjana Šarenac Vulović, Filip Radotić, Zorica Tončić, Maja Živković, Nenad Petrović
AIM: We aimed to analyze the effects of adjunctive posterior sub-Tenon capsule triamcinolone acetonide injection in the treatment of intermediate uveitis macular edema in multiple sclerosis patients that could not be controlled by systemic corticosteroid medications and immunomodulators. METHODS: The study included 30 eyes of 25 patients with multiple sclerosis who received a posterior sub-Tenon injection of 40 mg/mL triamcinolone acetonide. Parameters monitored for therapy efficiency were best-corrected visual acuity, intraocular pressure, central foveal thickness (CFT), and fluorescein angiography (FA) scores...
March 22, 2017: Ophthalmic Research
https://www.readbyqxmd.com/read/28323646/endothelial-cells-and-lymphatics-at-the-interface-between-the-immune-and-central-nervous-systems-implications-for-multiple-sclerosis
#16
Céline Meyer, Guillaume Martin-Blondel, Roland S Liblau
PURPOSE OF REVIEW: The central nervous system (CNS) has a unique relationship with the immune system. This review highlights the distinct roles of lymphatic vessels and endothelial cells in the interface between CNS and immune cells and invites to revisit the concept of CNS immune privilege. RECENT FINDINGS: T cells can follow several routes to penetrate the CNS parenchyma but may also benefit, together with antigen-loaded presenting cells, from the newly described lymphatic network to exit the CNS...
March 18, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28323645/pediatric-multiple-sclerosis
#17
Anusha K Yeshokumar, Sona Narula, Brenda Banwell
PURPOSE OF REVIEW: This review discusses the epidemiologic factors involved in the pathogenesis of pediatric multiple sclerosis (MS), which have been the focus of numerous studies in the last several years. We also review the clinical features (including diagnostic evaluation and differential diagnosis) of, treatment approach to, and prognosis of pediatric MS. RECENT FINDINGS: Up to 10% of patients with MS have their initial demyelinating before the age of 18 years...
March 20, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28323224/progressive-multifocal-leukoencephalopathy-and-rheumatoid-arthritis-treatments
#18
Gaëlle Clavel, Antoine Moulignier, Luca Semerano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood...
March 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28322741/evidence-of-k-homeostasis-disruption-in-cellular-dysfunction-triggered-by-7-ketocholesterol-24s-hydroxycholesterol-and-tetracosanoic-acid-c24-0-in-158n-murine-oligodendrocytes
#19
Maryem Bezine, Meryam Debbabi, Thomas Nury, Rym Ben-Khalifa, Mohammad Samadi, Mustapha Cherkaoui-Malki, Anne Vejux, Jérôme de Sèze, Thibault Moreau, Mohamed El-Ayeb, Gérard Lizard
Imbalance in the homeostasis of K(+) ions has been reported to contribute to the pathogenesis of neurodegenerative diseases. 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC), and tetracosanoic acid (C24:0), often found at increased levels in patients with Alzheimer's disease, Multiple Sclerosis and X-ALD, are able to trigger numerous nerve cell dysfunctions. We therefore studied the impact of 7KC, 24S-OHC, and C24:0 on 158N murine oligodendrocytes, and determined their impact on K(+) homeostasis. The effects of 7KC, 24S-OHC and C24:0 on lipid membrane organization and membrane potential were examined with merocyanine 540 (MC540) and bis-(1,3-diethylthiobarbituric acid) trimethine oxonol (DiSBAC2(3)), respectively...
March 17, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28322606/cognitive-impairment-in-pediatric-onset-multiple-sclerosis-is-detected-by-the-brief-international-cognitive-assessment-for-multiple-sclerosis-and-computerized-cognitive-testing
#20
Leigh E Charvet, Michael Shaw, Ariana Frontario, Dawn Langdon, Lauren B Krupp
BACKGROUND: Cognitive impairment is a common and troubling feature of pediatric-onset multiple sclerosis (POMS). Brief cognitive assessment in the outpatient setting can identify and longitudinally monitor cognitive involvement so that early intervention is possible. OBJECTIVES: The goal of this study was to measure the sensitivity of two cognitive assessment approaches that are brief, repeatable, and suitable for clinical practice and for multicenter investigation...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
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