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Multiple sclerosis drugs

Anne Wickström, Maria Fagerström, Lucas Wickström, Gabriel Granåsen, Charlotte Dahle, Magnus Vrethem, Peter Sundström
BACKGROUND: Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. OBJECTIVES: To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. METHODS: Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar...
October 6, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Ke-Wei Tian, Fan Zhang, Hong Jiang, Beibei Wang, Shu Han
Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits...
October 19, 2016: Journal of Anatomy
Marisa P McGinley, Brandon P Moss, Jeffrey A Cohen
Monoclonal antibodies are a potent therapeutic approach for relapsing-remitting multiple sclerosis. This group of medications comprises diverse mechanisms of action resulting in both shared and unique adverse effects. Areas covered: The major trials and safety profiles of natalizumab, alemtuzumab, daclizumab, rituximab, and ocrelizumab are discussed. While each drug has a unique safety profile, one of the potential safety concerns for all of these drugs is infection, including for some progressive multifocal leukoencephalopathy...
October 19, 2016: Expert Opinion on Drug Safety
Chihiro Fujii, Takayuki Kondo, Hirofumi Ochi, Yoichiro Okada, Yuichiro Hashi, Tetsuya Adachi, Masaharu Shin-Ya, Sadayuki Matsumoto, Ryosuke Takahashi, Masanori Nakagawa, Toshiki Mizuno
Multiple sclerosis (MS) is a T cell-mediated autoimmune disease. Fingolimod, a highly effective disease-modifying drug for MS, retains CCR7(+) central memory T cells in which autoaggressive T cells putatively exist, in secondary lymphoid organs, although relapse may still occur in some patients. Here, we analyzed the T cell phenotypes of fingolimod-treated, fingolimod-untreated patients, and healthy subjects. The frequency of CD56(+) T cells and granzyme B-, perforin-, and Fas ligand-positive T cells significantly increased during fingolimod treatment...
October 18, 2016: Scientific Reports
Mathew Clement, James A Pearson, Stephanie Gras, Hugo A van den Berg, Anya Lissina, Sian Llewellyn-Lacey, Mark D Willis, Tamsin Dockree, James E McLaren, Julia Ekeruche-Makinde, Emma Gostick, Neil P Robertson, Jamie Rossjohn, Scott R Burrows, David A Price, F Susan Wong, Mark Peakman, Ania Skowera, Linda Wooldridge
CD8(+) T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8(+) T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8(+) T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8(+) T-cells are relatively CD8-independent...
October 17, 2016: Scientific Reports
Juncal Fernández-Orth, Petra Ehling, Tobias Ruck, Susann Pankratz, Majella-Sophie Hofmann, Peter Landgraf, Daniela C Dieterich, Karl-Heinz Smalla, Thilo Kähne, Guiscard Seebohm, Thomas Budde, Heinz Wiendl, Stefan Bittner, Sven G Meuth
K2P 5.1 channels (also called TASK-2 or KCNK5) have already been shown to be relevant in the pathophysiology of autoimmune disease since they are known to be upregulated on peripheral and central T lymphocytes of multiple sclerosis (MS) patients. Moreover, overexpression of K2P 5.1 channels in vitro provokes enhanced T-cell effector functions. However, the molecular mechanisms regulating intracellular K2P 5.1 channel trafficking are unknown so far. Thus, the aim of the study is to elucidate the trafficking of K2P 5...
October 15, 2016: Traffic
Samuel Lapalme-Remis, Gregory D Cascino
PURPOSE OF REVIEW: This article discusses structural and functional neuroimaging findings in patients with seizures and epilepsy. The indications for neuroimaging in these patients and the potential diagnostic utility of these studies are presented. RECENT FINDINGS: Patients presenting with new seizures typically require urgent imaging to rule out a critical underlying cause. MRI is the structural neuroimaging procedure of choice in individuals with epilepsy. Specific epilepsy protocols should be considered to increase the diagnostic yield of neuroimaging in patients with structural lesions associated with focal or generalized seizures...
October 2016: Continuum: Lifelong Learning in Neurology
Patrick Vermersch, Maria Trojano
BACKGROUND: Tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) is an add-on therapy for moderate-to-severe multiple sclerosis (MS)-related drug-resistant spasticity (MSS). AIM: The MOVE-2 EU study collected data from everyday clinical practice concerning the effectiveness and tolerability of THC:CBD. METHODS: This was an observational, prospective, multicentre, non-interventional study. Patients with resistant MSS prescribed add-on THC:CBD oromucosal spray according to approved labelling, were followed for 3 months...
October 13, 2016: European Neurology
Shengli Ma, Xue Rui, Peiyi Qi, Gangqiong Liu, Jing Yang
BACKGROUND: Poor sleep is common in patients with multiple sclerosis (MS). This study assessed the prevalence of poor sleep and investigated the potential impact factors that influence sleep quality of patients with MS. METHODS: A cross-sectional self-report survey of 231 patients with MS and 265 sex- and age-matched controls was conducted. Good sleepers and poor sleepers were separated by their global score on the Pittsburgh Sleep Quality Index (PSQI). Sociodemographic parameters, such as age, gender, and marital status, and clinical-demographic parameters, such as excessive daytime sleepiness (measured by the Epworth Sleepiness Scale), snoring, insomnia, obstructive sleep apnea, drugs, pain, depression, fatigue, and quality of life, were registered...
October 11, 2016: Sleep & Breathing, Schlaf & Atmung
Mark D Willis, Trevor P Pickersgill, Neil P Robertson, Richard W J Lee, Andrew D Dick, Ester Carreño
PURPOSE: The purpose of the study was to report a case of multiple sclerosis (MS)-associated uveitis refractory to conventional immunosuppressants, with subsequent remission following treatment with alemtuzumab. METHODS: Case report Patient was treated with intravenous alemtuzumab, a lymphocyte depleting anti-CD52 monoclonal antibody that has recently been approved for use in relapsing MS. RESULTS: A 17-year-old female presented with bilateral optic neuritis and subsequently bilateral intermediate uveitis and secondary macular oedema...
October 11, 2016: International Ophthalmology
Hai-Yun Xiao, Scott H Watterson, Charles M Langevine, Anurag S Srivastava, Soo S Ko, Yanlei Zhang, Robert Joseph Cherney, Weiwei Guo, John L Gilmore, James E Sheppeck, Dauh-Rurng Wu, Peng Li, Duraisamy Ramasamy, Pirama Nayagam Arunachalam, Arvind Mathur, Tracy L Taylor, David J Shuster, Kim W McIntyre, Ding Ren Shen, Melissa Yarde, Mary Ellen Cvijic, Anthony M Marino, Praveen V Balimane, Zheng Yang, Dana M Banas, Georgia Cornelius, Celia J D Arienzo, Bethanne M Warrack, Lois D Lehman-McKeeman, Luisa M Salter-Cid, Jenny H Xie, Joel C Barrish, Percy H Carter, Alaric J Dyckman, T G Murali Dhar
Fingolimod (1) is the first approved oral therapy for the treatment of relapsing remitting multiple sclerosis. While the phosphorylated metabolite of fingolimod was found to be a non-selective S1P receptor agonist, agonism specifically of S1P1 is responsible for the peripheral blood lymphopenia believed to be key to its efficacy. Identification of modulators that maintain activity on S1P1 while sparing activity on other S1P receptors could offer equivalent efficacy with reduced liabilities. We disclose in this paper a ligand based drug design approach that led to the discovery of a series of potent tricyclic agonists of S1P1 with selectivity over S1P3 and were efficacious in a pharmacodynamic model of suppression of circulating lymphocytes...
October 11, 2016: Journal of Medicinal Chemistry
Ahmed T Kurdi, Ribal Bassil, Marta Olah, Chuan Wu, Sheng Xiao, Mariko Taga, Michael Frangieh, Thomas Buttrick, William Orent, Elizabeth M Bradshaw, Samia J Khoury, Wassim Elyaman
RORγt is a master transcription factor of Th17 cells and considered as a promising drug target for the treatment of autoimmune diseases. Here, we show the guanine nucleotide exchange factor, Tiam1, and its cognate Rho-family G protein, Rac1, regulate interleukin (IL)17A transcription and autoimmunity. Whereas Tiam1 genetic deficiency weakens IL-17A expression partially and inhibits the development of experimental autoimmune encephalomyelitis (EAE), deletion of Rac1 in T cells exhibits more robust effects on Th17 cells and EAE...
October 11, 2016: Nature Communications
Shohei Murakami, Hozumi Motohashi
The KEAP1-NRF2 system is an inducible molecular mechanism enhancing transcriptions of several cytoprotective genes in response to xenobiotics and oxidative stress. Recently, the KEAP1-NRF2 system has been suggested to directly regulate a portion of the genes related to cell proliferation and differentiation. In hematopoietic cells, NRF2 activation plays a role in maintenance and cell fate determination of hematopoietic stem cells, as well as in maturation processes and homeostasis of megakaryocytes and erythrocytes...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Ismat Ullah Khan, Shivashankar Kattela, Abbas Hassan, Carlos Roque Duarte Correia
A novel, efficient and enantioselective Heck-Matsuda desymmetrization of non-activated cyclopentene-fused spiro-pyrrolidinones was developed. The reaction provided the Heck products in good to excellent yields and selectivities and tolerated a variety of functional groups in arenediazonium tetrafluoroborates (12 examples) with respect to its electronics and substitution patterns. This methodology was successfully applied in the concise enantioselective total synthesis of VPC01091 (2b), a drug candidate for the treatment of multiple sclerosis...
October 12, 2016: Organic & Biomolecular Chemistry
Anju Singh, Mudasir Maqbool, Mohammad Mobashir, Nasimul Hoda
Malaria is a critical human disease with extensive exploration yet unestablished due to occurrence of frequent drug resistance. This aspect of malaria pharmacology calls for the introduction of new antimalarial. The drugs reported till date targeted different stages of the parasites in order to stop their growth and proliferation. Beside this, various drugs that could inhibit the imperative enzymes of the parasite have also been reported. Amid them, dihydroorotate dehydrogenase (DHODH) has a key worth. DHODH is involved in the de novo pyrimidine biosynthesis of the malarial parasite which acts as a primary source of energy for its survival...
September 27, 2016: European Journal of Medicinal Chemistry
Chiara Cordiglieri, Fulvio Baggi, Pia Bernasconi, Dimos Kapetis, Elisa Faggiani, Alessandra Consonni, Francesca Andreetta, Rita Frangiamore, Paolo Confalonieri, Carlo Antozzi, Renato Mantegazza
Multiple Sclerosis (MS) is an inflammatory disease with neurodegenerative alterations, ultimately progressing to neurological handicap. Therapies are effective in counteracting inflammation but not neurodegeneration. Biomarkers predicting disease course or treatment response are lacking. We investigated whether altered gene and protein expression profiles were detectable in the peripheral blood of 78 relapsing remitting MS (RR-MS) patients treated by disease-modifying therapies. A discovery/validation study on RR-MS responsive to glatiramer acetate identified 8 differentially expressed genes: ITGA2B, ITGB3, CD177, IGJ, IL5RA, MMP8, P2RY12, and S100β...
October 5, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Samira Abbasi, Nasrollah Alimohammadi, Saeid Pahlavanzadeh
BACKGROUND: Multiple sclerosis is accompanied by secondary clinical signs such as insomnia. Considering the side effects of drugs and also increasing acceptability of psychotherapy methods in health systems, we aimed to determine the effect of group cognitive behavioral therapy on the quality of sleep in women with multiple sclerosis in 2014. METHODS: This study is a randomized controlled clinical conducted on 72 women with multiple sclerosis who referred to medical centers of Isfahan...
October 2016: International Journal of Community Based Nursing and Midwifery
Andrew T Placzek, Skylar J Ferrara, Meredith D Hartley, Hannah S Sanford-Crane, J Matthew Meinig, Thomas S Scanlan
There is currently great interest in developing drugs that stimulate myelin repair for use in demyelinating diseases such as multiple sclerosis. Thyroid hormone plays a key role in stimulating myelination during development and also controls the expression of important genes involved in myelin repair in adults. Because endogenous thyroid hormone in excess lacks a generally useful therapeutic index, it is not used clinically for indications other than hormone replacement; however, selective thyromimetics such as sobetirome offer a therapeutic alternative...
September 16, 2016: Bioorganic & Medicinal Chemistry
Alessandra Bua, Melania Ruggeri, Stefania Zanetti, Paola Molicotti
Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis...
October 4, 2016: Medical Microbiology and Immunology
Ludmila A Kasatkina
4-aminopyridine is commonly used to stimulate neurotransmitter release resulting from sustained plasma membrane depolarization and Ca(2+)-influx from the extracellular space. This paper elucidated unconventional mechanism of 4-aminopyridine-stimulated glutamate release from neurons and non-neuronal cells which proceeds in the absence of external Ca(2+). In brain nerve terminals, primary neurons and platelets 4-aminopyridine induced the exocytotic release of glutamate that was independent of external Ca(2+) and was triggered by the sequestration of Ca(2+) from intracellular stores...
October 5, 2016: Scientific Reports
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