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https://www.readbyqxmd.com/read/28724999/x-ray-phase-contrast-tomography-reveals-early-vascular-alterations-and-neuronal-loss-in-a-multiple-sclerosis-model
#1
A Cedola, A Bravin, I Bukreeva, M Fratini, A Pacureanu, A Mittone, L Massimi, P Cloetens, P Coan, G Campi, R Spanò, F Brun, V Grigoryev, V Petrosino, C Venturi, M Mastrogiacomo, Nicole Kerlero de Rosbo, A Uccelli
The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627962/plasma-neurofilament-light-chain-levels-in-patients-with-ms-switching-from-injectable-therapies-to-fingolimod
#2
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/28560740/acutely-damaged-axons-are-remyelinated-in-multiple-sclerosis-and-experimental-models-of-demyelination
#3
Verena Schultz, Franziska van der Meer, Claudia Wrzos, Uta Scheidt, Erik Bahn, Christine Stadelmann, Wolfgang Brück, Andreas Junker
Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage...
August 2017: Glia
https://www.readbyqxmd.com/read/28512753/serum-neurofilament-light-a-biomarker-of-neuronal-damage-in-multiple-sclerosis
#4
COMPARATIVE STUDY
Giulio Disanto, Christian Barro, Pascal Benkert, Yvonne Naegelin, Sabine Schädelin, Antonella Giardiello, Chiara Zecca, Kaj Blennow, Henrik Zetterberg, David Leppert, Ludwig Kappos, Claudio Gobbi, Jens Kuhle
OBJECTIVE: Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS). METHODS: sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow-up = 3...
June 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28444098/the-cerebrospinal-fluid-in-multiple-sclerosis-far-beyond-the-bands
#5
Renan Barros Domingues, Gustavo Bruniera Peres Fernandes, Fernando Brunale Vilela de Moura Leite, Charles Peter Tilbery, Rodrigo Barbosa Thomaz, Gisele Sampaio Silva, Cristóvão Luis Pitangueira Mangueira, Carlos Augusto Senne Soares
The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency...
January 2017: Einstein
https://www.readbyqxmd.com/read/28396093/what-s-new-about-oral-treatments-in-multiple-sclerosis-immunogenetics-still-under-question
#6
REVIEW
Cristiana Pistono, Cecilia Osera, Chiara Boiocchi, Giulia Mallucci, Mariaclara Cuccia, Roberto Bergamaschi, Alessia Pascale
Multiple Sclerosis (MS) is a chronic pathology affecting the Central Nervous System characterized by inflammatory processes that lead to demyelination and neurodegeneration. In MS treatment, disease modifying therapies (DMTs) are essential to reduce disease progression by suppressing the inflammatory response responsible for promoting lesion formation. Recently, in addition to the classical injectable DMTs like Interferons and Glatiramer acetate, new orally administered drugs have been approved for MS therapy: dimethyl fumarate, teriflunomide and fingolimod...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28360804/affective-temperament-profiles-in-patients-with-multiple-sclerosis-association-with-mood-disorders
#7
Adile Özkan, Kürşat Altinbaş, Emine Rabia Koç, Halil Murat Şen, Handan Işın Özişik Karaman
INTRODUCTION: The aim of the present study was to screen for bipolarity and to investigate the affective temperaments of patients with multiple sclerosis (MS) and the possible association between the clinical and demographic characteristics of MS patients and temperament profiles. METHODS: A total of 65 patients with MS and 66 healthy volunteers completed the 32-item hypomania checklist (HCl-32), the Mood Disorder Questionnaire (MDQ), and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) tests...
December 2016: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/28321351/bilateral-birdshot-retinochoroiditis-and-retinal-astrocytoma
#8
Sunil Mamtora, Yun Wong, Dugald Bell, Teresa Sandinha
Background. This case highlights the importance of recognising multiple pathologies within the eye which may not necessarily be linked. Both birdshot retinochoroiditis and astrocytoma are rare conditions. The case underlines the need for early identification and treatment of birdshot retinochoroiditis with steroids and disease modifying drugs. Astrocytoma in the absence of tuberous sclerosis is also uncommon. Case Presentation. A 36-year-old male presented with 3-month history of bilateral progressive flashing lights and floaters...
2017: Case Reports in Ophthalmological Medicine
https://www.readbyqxmd.com/read/28116578/innate-immunity-in-systemic-sclerosis
#9
REVIEW
Christopher Dowson, Nathan Simpson, Laura Duffy, Steven O'Reilly
PURPOSE OF REVIEW: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease which has defined three hallmarks: Small vessel vasculopathy, production of autoantibodies and fibroblast dysfunction. The exact aetiology of the disease remains unknown, due to the complex nature of the cellular signalling pathways involved. However, there is strong and consistent evidence that the innate system, in particular toll-like receptor signalling, is contributing to the progression and perhaps onset of systemic sclerosis...
January 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28018358/endothelial-response-to-glucocorticoids-in-inflammatory-diseases
#10
REVIEW
Karolina A Zielińska, Laura Van Moortel, Ghislain Opdenakker, Karolien De Bosscher, Philippe E Van den Steen
The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27904491/intravenous-transplantation-of-mouse-embryonic-stem-cells-attenuates-demyelination-in-an-icr-outbred-mouse-model-of-demyelinating-diseases
#11
Kidsadagon Pringproa, Anucha Sathanawongs, Chananthida Khamphilai, Sarocha Sukkarinprom, Apichart Oranratnachai
Induction of demyelination in the central nervous system (CNS) of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. However, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intravenous cell transplantation in the present developed mouse model...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27823573/the-sphingosine-1-phosphate-signaling-pathway-in-epilepsy-a-possible-role-for-the-immunomodulator-drug-fingolimod-in-epilepsy-treatment
#12
Antonio Leo, Rita Citraro, Rosario Marra, Ernesto Palma, Eugenio Donato Di Paola, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G protein-coupled S1P receptor. Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying therapy that has been approved for the treatment of multiple sclerosis. Magnetic resonance imaging data suggest that fingolimod may be effective in multiple sclerosis MS by preventing blood-brain barrier disruption and brain atrophy...
November 4, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27787906/cerebrospinal-fluid-biomarkers-as-a-measure-of-disease-activity-and-treatment-efficacy-in-relapsing-remitting-multiple-sclerosis
#13
Lenka Novakova, Markus Axelsson, Mohsen Khademi, Henrik Zetterberg, Kaj Blennow, Clas Malmeström, Fredrik Piehl, Tomas Olsson, Jan Lycke
Cerebrospinal fluid (CSF) biomarkers can reflect different aspects of the pathophysiology of relapsing-remitting multiple sclerosis (RRMS). Understanding the impact of different disease modifying therapies on the CSF biomarker profile may increase their implementation in clinical practice and their appropriateness for monitoring treatment efficacy. This study investigated the influence of first-line (interferon beta) and second-line (natalizumab) therapies on seven CSF biomarkers in RRMS and their correlation with clinical and radiological outcomes...
April 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27316241/reduced-inflammation-in-relapsing-remitting-multiple-sclerosis-after-therapy-switch-to-rituximab
#14
MULTICENTER STUDY
Pierre de Flon, Martin Gunnarsson, Katarina Laurell, Lars Söderström, Richard Birgander, Thomas Lindqvist, Wolfgang Krauss, Ann Dring, Joakim Bergman, Peter Sundström, Anders Svenningsson
OBJECTIVE: To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS). METHOD: Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study...
July 12, 2016: Neurology
https://www.readbyqxmd.com/read/27191526/further-understanding-of-the-immunopathology-of-multiple-sclerosis-impact-on-future-treatments
#15
REVIEW
Vikram Bhise, Suhayl Dhib-Jalbut
INTRODUCTION: The understanding of the immunopathogenesis of multiple sclerosis (MS) has expanded with more research into T-cell subtypes, cytokine contributors, B-cell participation, mitochondrial dysfunction, and more. Treatment options have rapidly expanded with three relatively recent oral therapy alternatives entering the arena. AREAS COVERED: In the following review, we discuss current mechanisms of immune dysregulation in MS, how they relate to current treatments, and the impact these findings will have on the future of therapy...
October 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27116719/promising-oral-compounds-for-the-treatment-of-multiple-sclerosis-a-glance-into-the-future
#16
Bernhard F Décard, Tobias Derfuss
Recently, there have been major advances in the development of disease-modifying treatments for multiple sclerosis (MS) and new promising treatment compounds are on the horizon. The available drugs mainly target inflammatory components of MS; hence, there is an urgent need for new treatment approaches that focus on the neurodegenerative aspects of the disease. Innovative study designs and biomarkers such as neurofilament light chain and brain atrophy measurement could help to identify neuroprotective treatments for the progressive phase of MS...
April 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27058222/steering-through-complexity-management-approaches-in-multiple-sclerosis
#17
Bruce A C Cree, Hans-Peter Hartung
PURPOSE OF REVIEW: This review evaluates current and late-phase developing therapies for multiple sclerosis in regard to therapeutic efficacy and patient safety in light of recent published and presented observations from 2015. RECENT FINDINGS: We describe data that provide supportive evidence for comparisons of therapeutic efficacy of multiple sclerosis therapies and review available data on rare but serious adverse events associated with these therapies. SUMMARY: Serious adverse events that are sometimes rare and unpredictable may substantially alter current approaches to multiple sclerosis treatments...
June 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27056200/clinicopathological-characteristics-and-outcomes-of-light-chain-deposition-disease-an-analysis-of-48-patients-in-a-single-chinese-center
#18
Xiao Mei Li, Hao Chen Rui, Dan Dan Liang, Feng Xu, Shao Shan Liang, Xiao Dong Zhu, Xiang Hua Huang, Zhi Hong Liu, Cai Hong Zeng
To explore the clinicopathological characteristics and outcomes of light chain deposition disease (LCDD) in a Chinese population, we retrospectively studied the clinicopathological data, treatment, and outcomes of 48 patients with biopsy-proven LCDD from a single center. Among the patients, there were 29 males and 19 females, with an average age of 51 years. The patients presented with hypertension (79.2 %), edema (60.4 %), renal insufficiency (95.8 %), anemia (93.8 %), nephrotic proteinuria (≥3.0 g/24 h) (44...
May 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27048376/preclinical-models-of-multiple-sclerosis-advantages-and-limitations-towards-better-therapies
#19
REVIEW
Alessandro Didonna
Multiple sclerosis (MS) is a disease of the central nervous system (CNS) with an unknown etiology. MS complex pathophysiology-characterized by CNS inflammation, demyelination and axonal injury-has made its modeling in experimental systems particularly problematic. Moreover, the evidence that MS does not naturally occur in other species has further complicated MS preclinical studies. Through the years, several MS in vivo models have been developed. Experimental autoimmune encephalomyelitis (EAE) represents the most widely used MS experimental model and relies upon the autoimmune paradigm to explore MS neuropathology...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27034475/advances-in-clinical-determinants-and-neurological-manifestations-of-b-vitamin-deficiency-in-adults
#20
REVIEW
GianPietro Sechi, Elia Sechi, Chiara Fois, Neeraj Kumar
B vitamin deficiency is a leading cause of neurological impairment and disability throughout the world. Multiple B vitamin deficiencies often coexist, and thus an understanding of the complex relationships between the different biochemical pathways regulated in the brain by these vitamins may facilitate prompter diagnosis and improved treatment. Particular populations at risk for multiple B vitamin deficiencies include the elderly, people with alcoholism, patients with heart failure, patients with recent obesity surgery, and vegetarians/vegans...
May 2016: Nutrition Reviews
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