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https://www.readbyqxmd.com/read/28635362/costs-and-effectiveness-of-fingolimod-versus-alemtuzumab-in-the-treatment-of-highly-active-relapsing-remitting-multiple-sclerosis-in-the-uk-retreatment-discount-and-disutility
#1
Stephen M Montgomery, Jeanette Kusel, Richard Nicholas, Nicholas Adlard
OBJECTIVE: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod or may be considered for alemtuzumab. Previous economic modelling used Markov models; applying one alternative technique, discrete event simulation (DES) modelling, allows retreatment and long-term adverse events (AEs) to be included in the analysis. METHODS: A DES was adapted to model relapse-triggered retreatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous one year Markov cycles...
June 21, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28633994/t-lymphocytes-infiltration-promotes-blood-brain-barrier-injury-after-experimental-intracerebral-hemorrhage
#2
Xuan Zhang, Wei Liu, Jichao Yuan, Haitao Zhu, Yang Yang, Zexian Wen, Yaxing Chen, Lan Li, Jiangkai Lin, Hua Feng
T lymphocytes migrate into the brain after intracerebral hemorrhage (ICH) and promote cerebral inflammation, thus exacerbating neuronal injury. However, the relationship between of T lymphocytes infiltration and blood-brain barrier (BBB) injury after ICH has not been clarified. In this study, we investigated the spatial-temporal distribution of infiltrating T lymphocytes after ICH in C57BL/6 mice by immunofluorescence and flow cytometry, and the accompanying change rules of BBB permeability were detected by Evans blue dye leakage and tight junction protein expression...
June 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28629398/anaplastic-astrocytoma-mimicking-progressive-multifocal-leucoencephalopathy-a-case-report-and-review-of-the-overlapping-syndromes
#3
Ema Kantorová, Michal Bittšanský, Štefan Sivák, Eva Baranovičová, Petra Hnilicová, Vladimír Nosáľ, Daniel Čierny, Kamil Zeleňák, Wolfgang Brück, Egon Kurča
BACKGROUND: Co-occurrence of multiple sclerosis (MS) and glial tumours (GT) is uncommon although occasionally reported in medical literature. Interpreting the overlapping radiologic and clinical characteristics of glial tumours, MS lesions, and progressive multifocal leukoencephalopathy (PML) can be a significant diagnostic challenge. CASE PRESENTATION: We report a case of anaplastic astrocytoma mimicking PML in a 27-year-old patient with a 15-year history of MS...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28627962/plasma-neurofilament-light-chain-levels-in-patients-with-ms-switching-from-injectable-therapies-to-fingolimod
#4
Fredrik Piehl, Ingrid Kockum, Mohsen Khademi, Kaj Blennow, Jan Lycke, Henrik Zetterberg, Tomas Olsson
BACKGROUND: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). OBJECTIVE: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. METHODS: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28627375/modulation-of-sphingosine-1-phosphate-receptor-ameliorates-harmaline-induced-essential-tremor-in-rat
#5
Narjes Dahmardeh, Majid Asadi-Shekaari, Shokouh Arjmand, Tajpari Kalantaripour, Mohsen Basiri, Mohammad Shabani
Essential tremor (ET) is one of the most common movement disorders with unknown etiology. Despite lack of effective clinical treatments, some potential therapeutic factors and modulation of some neurotransmitters have been utilized to ameliorate motor symptoms in the animal models of tremor. In the current study, male Wistar rats (n=10 in each group) weighing 40-60g were divided into vehicle control groups (saline or DMSO), saline/DMSO+harmaline (30mg/kg, i.p.)+fingolimod (FTY720) (1mg/kg, i.p, 1h before harmaline injection) groups...
June 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28626524/-19-f-nmr-based-dual-site-reporter-assay-for-the-discovery-and-distinction-of-catalytic-and-allosteric-kinase-inhibitors
#6
Lukasz Skora, Wolfgang Jahnke
In modern kinase drug discovery, allosteric inhibitors have become a focus of attention due to their potential selectivity, but such compounds are difficult to identify. Here we describe an NMR-based competition assay using (19)F-containing reporter molecules, which allows for rapid identification and discrimination between ATP-competitive and allosteric kinase inhibitors. We illustrate the principle of such a dual-site competition assay with the example of catalytic and allosteric ABL1 kinase inhibitors. The assay can also be used to identify and characterize mixed binding modes of well-known drugs, as shown for crizotinib and fingolimod...
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28619738/fingolimod-associated-macular-oedema
#7
Kirti Madhukar Jasani, Nazar Sharaf, David Rog, Tariq Aslam
No abstract text is available yet for this article.
June 15, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28619437/fatigue-evaluation-in-fingolimod-treated-patients-an-observational-study
#8
Marion Masingue, Rabab Debs, Elisabeth Maillart, Valérie Delvaux, Catherine Lubetzki, Jean-Sébastien Vidal, Caroline Papeix
BACKGROUND: Fatigue is one of the most disabling symptoms in Multiple Sclerosis (MS) patients and is associated with a low quality of life. Fingolimod (Fg), a sphingosine 1-phosphate receptor modulator, is the first oral MS disease modifying treatment. Little is known about its effect on fatigue. To assess the impact of Fg on fatigue within the first 6 months of treatment in MS patients, we conducted a prospective, open label study, in real life setting. METHODS: Change of Modified Fatigue Impact Scale (MFIS) between Fg treatment start and at 6 months was used as a first outcome...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28619436/tumefactive-demyelinating-lesions-a-comprehensive-review
#9
REVIEW
Hussein Algahtani, Bader Shirah, Ali Alassiri
Tumefactive multiple sclerosis or tumefactive demyelinating lesion (TDL) is one of the rare variants of multiple sclerosis (MS) posing a diagnostic challenge and a therapeutic enigma since it is difficult to distinguish from a true central nervous system (CNS) neoplasm or other CNS lesions on magnetic resonance imaging (MRI). The prevalence of TDL is estimated to be 1-3/1000 cases of MS with an annual incidence of 0.3/100,000. This could be an underestimate due to unavailability of a global MS registry and under-reporting of this condition...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28619430/effect-of-fingolimod-fty720-on-choroidal-thickness-in-patients-with-multiple-sclerosis
#10
Ali Kal, Mahmut Oğuz Ulusoy, Bahriye Horasanlı, Şefik Cezairlioğlu, Öznur Kal
OBJECTIVE: Using spectral domain optical coherence tomography (SD-OCT), to compare the choroidal thickness in a healthy population (group 1), with newly diagnosed multiple sclerosis (MS) patients (group 2), with MS patients who underwent β-interferon monotherapy (group 3) and MS patients who underwent fingolimod therapy for 1 year (group 4) METHODS: Twenty-five control subjects (25 eyes), 24 newly diagnosed (24 eyes) MS patients, 22 MS patients who underwent fingolimod monotherapy for 1 year (22 eyes), and 24 MS patients who underwent β-interferon monotherapy for 1 year (24 eyes) were included in this study...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28617365/-immune-reconstitution-inflammatory-syndrome-and-rebound-syndrome-in-multiple-sclerosis-patients-who-stopped-disease-modification-therapy-current-understanding-and-a-case-report
#11
A N Belova, M V Rasteryaeva, N I Zhulina, E M Belova, A N Boyko
More and more multiple sclerosis patients have been receiving treatment with new immunomodulatory drugs. Its discontinuation because of side-effects, lack of efficacy or pregnancy has been increasing as well. This paper reviews such severe complications of natalizumab and fingolimod cessation as immune reconstitution inflammatory syndrome (IRIS) and rebound. The short history, immunopathogenesis and diagnostic criteria of IRIS in individuals with human immunodeficiency virus infection are covered. Clinical and radiological presentations as well as possible pathogenic mechanisms of IRIS in patients treated with natalizumab and fingolimod are discussed...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28616447/natalizumab-pml-survivors-with-subsequent-ms-treatment-clinico-radiologic-outcome
#12
Elisabeth Maillart, Jean-Sebastien Vidal, David Brassat, Bruno Stankoff, Agnès Fromont, Jérôme de Sèze, Frédéric Taithe, Pierre Clavelou, Bertrand Bourre, Valérie Delvaux, Audrey Rico, Pierre Labauge, Ayman Tourbah, Christine Lebrun, Jean Pelletier, Thibault Moreau, Céline Louapre, Catherine Lubetzki, Caroline Papeix
OBJECTIVE: To describe the clinico-radiologic outcome of MS patients with natalizumab-related progressive multifocal leukoencephalopathy (Nz-PML) surviving and receiving disease-modifying therapy (DMT). METHODS: We describe clinical and radiologic evolution of Nz-PML survivors in an observational retrospective multicenter cohort to clarify the effect of different subsequent MS DMT strategies. Twenty-three patients from 11 centers were analyzed. Outcomes were (1) clinical efficacy of post-PML MS DMT, (2) radiologic efficacy of post-PML MS DMT, (3) radiologic evolution of PML lesion, and (4) disability progression...
May 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28607567/the-outbreak-fingolimod-cardiovascular-side-effects-in-relapsing-remitting-multiple-sclerosis-patient-a-longitudinal-study-in-an-iranian-population
#13
Morteza Abdar, Payam Ebrahimifar, Masoud Etemadifar
BACKGROUND: Fingolimod (FTY-720) has shown efficacy in relapsing multiple sclerosis (MS), while some side effects of this drug have been recognized that the most important is cardiovascular side effects. The aim of this study was to evaluate the cardiovascular side effects of FTY-720. However, the effect of fingolimod on cardiac has not been well recognized. This study was designed to evaluate the cardiovascular side effects of fingolimod in relapsing-remitting multiple sclerosis (RRMS) patient in an Iranian population...
November 2016: ARYA Atherosclerosis
https://www.readbyqxmd.com/read/28607130/s1pr1-sphingosine-1-phosphate-receptor-1-signaling-regulates-blood-flow-and-pressure
#14
Anna Cantalupo, Antonella Gargiulo, Elona Dautaj, Catherine Liu, Yi Zhang, Timothy Hla, Annarita Di Lorenzo
Nitric oxide is one of the major endothelial-derived vasoactive factors that regulate blood pressure (BP), and the bioactive lipid mediator S1P (sphingosine-1-phosphate) is a potent activator of endothelial nitric oxide synthase through G protein-coupled receptors. Endothelial-derived S1P and the autocrine/paracrine activation of S1PR (S1P receptors) play an important role in preserving vascular functions and BP homeostasis. Furthermore, FTY720 (fingolimod), binding to 4 out of 5 S1PRs recently approved by the Food and Drug Administration to treat autoimmune conditions, induces a modest and transient decrease in heart rate in both animals and humans, suggesting that drugs targeting sphingolipid signaling affect cardiovascular functions in vivo...
June 12, 2017: Hypertension
https://www.readbyqxmd.com/read/28597710/comparing-treatment-options-for-chronic-inflammatory-neuropathies-and-choosing-the-right-treatment-plan
#15
Eduardo Nobile-Orazio, Francesca Gallia, Fabrizia Terenghi, Mariangela Bianco
Chronic inflammatory neuropathies are disorders caused by an immune response to peripheral nerve. They include chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and neuropathy associated with anti-MAG IgM monoclonal gammopathy and other less frequent neuropathies. Several immune therapies have been proven to be effective in these neuropathies even if the best therapeutic option is still unsettled. Areas covered: The authors reviewed the literature to compare the efficacy and safety of currently used immune therapies in these neuropathies...
June 9, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28577576/sphingosine-1-phosphate-receptor-3-and-rhoa-signaling-mediate-inflammatory-gene-expression-in-astrocytes
#16
Stephanie S Dusaban, Jerold Chun, Hugh Rosen, Nicole H Purcell, Joan Heller Brown
BACKGROUND: Sphingosine 1-phosphate (S1P) signals through G protein-coupled receptors to elicit a wide range of cellular responses. In CNS injury and disease, the blood-brain barrier is compromised, causing leakage of S1P from blood into the brain. S1P can also be locally generated through the enzyme sphingosine kinase-1 (Sphk1). Our previous studies demonstrated that S1P activates inflammation in murine astrocytes. The S1P1 receptor subtype has been most associated with CNS disease, particularly multiple sclerosis...
June 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28574147/the-pak1-signalling-pathway-in-cardiac-disease-from-mechanistic-study-to-therapeutic-exploration
#17
REVIEW
Yanwen Wang, Shunyao Wang, Ming Lei, Mark Boyett, Hoyee Tsui, Wei Liu, Xin Wang
p21-activated kinase 1 (Pak1) is a member of the highly conserved family of serine/threonine protein kinases regulated by Ras-related small G-proteins, Cdc42/Rac1. It has been previously demonstrated to be involved in cardiac protection. Based on recent studies, this review assembles an overview of the role of Pak1 in cardiac diseases including disrupted Ca(2+) homoeostasis related cardiac arrhythmias, β-adrenergic stress and pressure overload-induced hypertrophy, and ischemia/reperfusion injury. These findings demonstrate the importance of Pak1 regulation through phosphorylation and transcriptional modification of hypertrophy and/or arrhythmia-related genes...
June 2, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28570482/targeting-the-s1p-s1pr1-axis-mitigates-cancer-induced-bone-pain-and-neuroinflammation
#18
Shaness A Grenald, Timothy M Doyle, Hong Zhang, Lauren M Slosky, Zhoumou Chen, Tally M Largent-Milnes, Sarah Spiegel, Todd W Vanderah, Daniela Salvemini
Metastatic bone pain is the single most common form of cancer pain, and persists as a result of peripheral and central inflammatory, as well as, neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P)...
May 31, 2017: Pain
https://www.readbyqxmd.com/read/28569122/rationale-and-design-of-combination-of-an-immune-modulator-fingolimod-with-alteplase-bridging-with-mechanical-thrombectomy-in-acute-ischemic-stroke-famtais-trial
#19
Sheng Zhang, Ying Zhou, Ruiting Zhang, Meixia Zhang, Bruce Campbell, Longting Lin, Fu-Dong Shi, Min Lou
Rationale In acute ischemic stroke patients with large vessel occlusion, although reperfusion within 6 h after stroke onset using combined intravenous alteplase and mechanical thrombectomy (bridging therapy) can improve functional outcome, still approximately 50% patients suffer disability which may result from reperfusion injury. Proof-of-concept clinical trials have indicated that the sphingosine-1-phosphate receptor modulator fingolimod may be efficacious in attenuating brain inflammation and improving clinical outcomes in acute ischemic stroke patients as a single therapy beyond 4...
January 1, 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/28543950/approach-to-fingolimod-induced-lymphopenia-in-multiple-sclerosis-patients-do-we-have-a-roadmap
#20
Jagannadha Avasarala, Sandip Jain, Enrique Urrea-Mendoza
No abstract text is available yet for this article.
May 25, 2017: Journal of Clinical Pharmacology
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