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https://www.readbyqxmd.com/read/29222803/synthesis-of-biocompatible-titanate-nanofibers-for-effective-delivery-of-neuroprotective-agents
#1
Asya Ozkizilcik, Roger Williams, Z Ryan Tian, Dafin F Muresanu, Aruna Sharma, Hari S Sharma
Nanoscience provides us with new opportunities to develop nanotechnologies for treating, in particular, central nervous system disorders such as Alzheimer disease and multiple sclerosis. From a methodological point of view, it is challenging to deliver drugs effectively across the blood-brain barrier and blood-cerebrospinal fluid barrier. Our 10-year data and reports from both in vivo and in vitro studies, however, have consistently proved that therapeutic drugs of different types can be generally loaded in/on the nanocarriers for targeted and programmable deliveries to the central nervous system with a high degree of efficacy...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222794/active-induction-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#2
Gabriella Contarini, Pietro Giusti, Stephen D Skaper
The protocol in this chapter presents a method to actively induce experimental autoimmune encephalomyelitis (EAE), one of the most widely used animal models to study efficacy of potential drugs for treatment of multiple sclerosis. Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system and the most common cause of chronic neurological impairment in young people. In this model EAE is induced in female C57BL/6 mice by immunization with an emulsion of myelin oligodendrocyte glycoprotein (fragment 35-55) in complete Freund's adjuvant, followed by administration of pertussis toxin in phosphate-buffered saline...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29213032/-staging-of-neuroplasticity-alterations-during-epileptogenesis-temporal-lobe-epileply-as-an-example
#3
N V Gulyaeva
Using temporal lobe epilepsy as an example, staging of long term plasticity in the hippocampus is considered. Major stages demonstrating opposite alterations in neuroplasticity are active epileptogenesis and the period of established temporal lobe epilepsy. During the epileptogenesis, multiple events resulting in forming of epileptic neuronal nets occur: changes in glutamatergic and GABAergic neurons, increase of aberrant neurogenesis, axonal sprouting and dendrite remodeling, particularly, supported by an excessive enhancement of the BDNF system in specific hippocampal regions...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29210147/drug-exposure-and-the-risk-of-multiple-sclerosis-a-systematic-review
#4
REVIEW
Heather Y Yong, Kyla A McKay, Cole G J Daley, Helen Tremlett
BACKGROUND: Several environmental and lifestyle factors have been associated with multiple sclerosis (MS) risk, including some pharmacological treatments. We systematically reviewed the literature on prescription drug exposure and MS risk. METHODS: Six databases were searched for original observational studies reporting drug exposure and MS risk published before 2017. RESULTS: Thirteen articles fulfilled inclusion criteria. Exposure to neither amiloride nor valproic acid was associated with MS (adjusted hazard ratio (adj...
December 6, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/29205982/spasticity-or-periodic-limb-movements
#5
Jonathan Levy, Sarah Hartley, Elsa Mauruc-Soubirac, Antoine Leotard, Frederic Lofaso, Maria-Antonia Quera-Salva, Djamel Bensmail
BACKGROUND: Spasticity and spasms are distressing features of the upper motor neuron syndrome (UMNS) following spinal cord injuries (SCI) or multiple sclerosis (MS), and have common therapeutic implications. Despite an increase of antispastic drugs and strategies, sometimes up to the surgical implant of intrathecal baclofen pump, some patients still complain of disabling spasms, which poses diagnostic and therapeutic challenges. Although clinically similar, flexor spasms due to pyramidal tract disruption must be clearly differentiated from periodic limb movements (PLM), often accompanying restless leg syndrome (RLS) and occurring during sleep...
December 4, 2017: European Journal of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/29203302/immunomodulatory-effects-of-a-rationally-designed-peptide-mimetic-of-human-ifn%C3%AE-in-eae-model-of-multiple-sclerosis
#6
Mansour Poorebrahim, Matin Asghari, Mohammad Foad Abazari, Hassan Askari, Solmaz Sadeghi, Asghar Taheri-Kafrani, Mohammad Hossein Nasr-Esfahani, Pegah Ghoraeian, Maryam Nouri Aleagha, Seyed Shahriar Arab, Derek Kennedy, Alireza Montaseri, Mahsa Mehranfar, Nima Sanadgol
The efficiency of interferon beta (IFNβ)-based drugs is considerably limited due to their undesirable properties, especially high immunogenicity. In this study, for the first time we investigated the impact of a computationally designed peptide mimetic of IFNβ, called MSPEP27, in the animal model of MS. A peptide library was constructed using the Rosetta program based on the predominant IFNAR1-binding site of IFNβ. Molecular docking studies were carried out using ClusPro and HADDOCK tools. The GROMACS package was subsequently used for molecular dynamics (MD) simulations...
December 1, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29197515/fingolimod-anti-inflammatory-and-neuroprotective-effects-modulation-of-rage-axis-in-multiple-sclerosis-patients
#7
Zohara Sternberg, Channa Kolb, Kailash Chadha, Adam Nir, Raphael Nir, Rayan George, Joseph Johnson, Jinhee Yu, David Hojnacki
BACKGROUND: We investigated Fingolimod treatment effects on the RAGE (receptor for advanced glycation endproducts) axis in multiple sclerosis (MS) patients. The primary outcome of the study was whether Fingolimod treatment increases serum levels of the soluble RAGE isoforms, sRAGE and esRAGE - both being considered putative endogenous inhibitors of RAGE signaling. Additional variables were serum levels of RAGE ligands, the high mobility group box (HMGB)1 and pentosidine. METHODS: Serum levels of the study variables were measured by ELISA, and compared between baseline (before Fingolimod treatment) and 6 and 12 months post-drug treatment in 17 relapsing MS patients...
November 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29196883/magnesium-lithospermate-b-suppresses-lipopolysaccharide-induced-neuroinflammation-in-bv2-microglial-cells-and-attenuates-neurodegeneration-in-lipopolysaccharide-injected-mice
#8
Yaojun Tai, Yujiao Qiu, Zhicheng Bao
Chronic inflammation in the brain plays a critical role in major neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Microglia, the resident macrophages and intrinsic components of the central nervous system (CNS), appear to be the main effectors in this pathological process. Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae, which has been documented to protect neurons against multiple types of neuronal injury...
December 1, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29194580/a-systems-medicine-approach-reveals-disordered-immune-system-and-lipid-metabolism-in-multiple-sclerosis-patients
#9
Mehrdad Pazhouhandeh, Mohammad-Ali Sahraian, Seyed Davar Siadat, Abolfazl Fateh, Farzam Vaziri, Fatemeh Tabrizi, Faezeh Ajorloo, Arash Keshavarzi Arshadi, Elnaz Fatemi, Somaye Piri Gavgani, Fereidoun Mahboudi, Fatemeh Rahimi Jamnani
Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnosed relapsing-remitting MS patients (NDP) and those receiving disease modifying therapy (RP). Through a random peptide phage library, a panel of NDP- and RP-specific peptides was identified, producing two protein datasets visualized using Gephi, based on protein-protein interactions in the STRING database...
November 30, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29193293/functional-antagonism-of-sphingosine-1-phosphate-receptor-1-prevents-cuprizone-induced-demyelination
#10
SunJa Kim, Jacek Bielawski, Hyunmin Yang, Yu Kong, Beiyan Zhou, Jianrong Li
Recent evidence suggests that the oral drug Fingolimod (FTY720) for relapsing-remitting multiple sclerosis (MS) may act directly on the central nervous system (CNS) and modulate disease pathogenesis and progression in experimental models of MS. However, the specific subtype of sphingosine-1-phosphate (S1P) receptors that mediates the effect of FTY720 on the CNS cells has not been fully elucidated. Here, we report that S1P receptor 1 (S1PR1) is elevated in reactive astrocytes in an autoimmunity independent mouse model of MS and that selective S1PR1 modulation is sufficient to ameliorate the loss of oligodendrocytes and demyelination...
November 29, 2017: Glia
https://www.readbyqxmd.com/read/29183628/the-pharmacokinetics-of-fumaric-acid-esters-reveal-their-in-vivo-effects
#11
REVIEW
Ulrich Mrowietz, Peter John Morrison, Ina Suhrkamp, Margaret Kumanova, Bernd Clement
Fumaric acid ester-based drugs are used for the treatment of psoriasis and multiple sclerosis. All licensed fumaric acid ester drugs contain dimethylfumarate (DMF) as the main active component. Due to the expanding use of oral DMF there is growing scientific interest in determining its as-yet-unknown mechanism of action. However, the pharmacology and chemistry of DMF are often not fully considered in the design and interpretation of experiments; namely, that while DMF is plasma-membrane permeable and has strong effects on many cell types in vitro, it is rapidly metabolized into membrane-impermeable monomethylfumarate (MMF) in vivo...
November 25, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29182993/lymphocyte-count-in-peripheral-blood-is-not-associated-with-the-level-of-clinical-response-to-treatment-with-fingolimod
#12
Yara Dadalti Fragoso, Tim Spelman, Cavit Boz, Raed Alroughani, Alessandra Lugaresi, Steve Vucic, Helmut Butzkueven, Murat Terzi, Eva Havrdova, Dana Horakova, Franco Granella, Javier Olascoaga, José Luis Sánchez-Menoyo, Eugenio Pucci, Michael Barnett, Joseph Bruno B Brooks, Jodi Haartsen
BACKGROUND: Fingolimod is an efficient and safe drug for treating relapsing-remitting multiple sclerosis (RRMS). In vivo, fingolimod is phosphorylated and binds to "sphingosine-1-phosphate"(S1P) receptors that are expressed in a wide range of cells, including lymphocytes. Under the effect of fingolimod, lymphocytes are retained in lymphoid tissues through the regulation of S1P1 receptors. The aim of the present study was to assess whether the degree of lymphopenia was correlated to the positive treatment response of RRMS patients with fingolimod...
November 22, 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29176975/targeting-cannabinoid-signaling-in-the-immune-system-high-ly-exciting-questions-possibilities-and-challenges
#13
REVIEW
Attila Oláh, Zoltán Szekanecz, Tamás Bíró
It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the "phytocannabinoids" [pCBs; e.g., (-)-trans-Δ9-tetrahydrocannabinol (THC), (-)-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances ["endocannabinoids" (eCB), e.g., arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol (2-AG), etc.]. These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29176956/meta-analysis-of-the-age-dependent-efficacy-of-multiple-sclerosis-treatments
#14
Ann Marie Weideman, Marco Aurelio Tapia-Maltos, Kory Johnson, Mark Greenwood, Bibiana Bielekova
Objective: To perform a meta-analysis of randomized, blinded, multiple sclerosis (MS) clinical trials, to test the hypothesis that efficacy of immunomodulatory disease-modifying therapies (DMTs) on MS disability progression is strongly dependent on age. Methods: We performed a literature search with pre-defined criteria and extracted relevant features from 38 clinical trials that assessed efficacy of DMTs on disability progression. We fit a linear regression, weighted for trial sample size, and duration, to examine the hypothesis that age has a defining effect on the therapeutic efficacy of immunomodulatory DMTs...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29172994/amiloride-does-not-protect-retinal-nerve-fibre-layer-thickness-in-optic-neuritis-in-a-phase-2-randomised-controlled-trial
#15
Justin B McKee, Charles L Cottriall, John Elston, Simon Epps, Nikos Evangelou, Stephen Gerry, Christopher Kennard, Yazhuo Kong, Abigail Koelewyn, Wilhelm Kueker, Maria Isabel Leite, Jacqueline Palace, Matthew Craner
BACKGROUND: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). OBJECTIVE: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). METHODS: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29168242/compositional-differences-between-copaxone-and-glatopa-are-reflected-in-altered-immunomodulation-ex-vivo-in-a-mouse-model
#16
Iris Grossman, Sarah Kolitz, Arthur Komlosh, Benjamin Zeskind, Vera Weinstein, Daphna Laifenfeld, Adrian Gilbert, Oren Bar-Ilan, Kevin D Fowler, Tal Hasson, Attila Konya, Kevin Wells-Knecht, Pippa Loupe, Sigal Melamed-Gal, Tatiana Molotsky, Revital Krispin, Galia Papir, Yousif Sahly, Michael R Hayden
Copaxone (glatiramer acetate, GA), a structurally and compositionally complex polypeptide nonbiological drug, is an effective treatment for multiple sclerosis, with a well-established favorable safety profile. The short antigenic polypeptide sequences comprising therapeutically active epitopes in GA cannot be deciphered with state-of-the-art methods; and GA has no measurable pharmacokinetic profile and no validated pharmacodynamic markers. The study reported herein describes the use of orthogonal standard and high-resolution physicochemical and biological tests to characterize GA and a U...
November 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29163185/orthostatic-intolerance-in-older-persons-etiology-and-countermeasures
#17
REVIEW
Nandu Goswami, Andrew P Blaber, Helmut Hinghofer-Szalkay, Jean-Pierre Montani
Orthostatic challenge produced by upright posture may lead to syncope if the cardiovascular system is unable to maintain adequate brain perfusion. This review outlines orthostatic intolerance related to the aging process, long-term bedrest confinement, drugs, and disease. Aging-associated illness or injury due to falls often leads to hospitalization. Older patients spend up to 83% of hospital admission lying in bed and thus the consequences of bedrest confinement such as physiological deconditioning, functional decline, and orthostatic intolerance represent a central challenge in the care of the vulnerable older population...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29161897/status-epilepticus-and-multiple-sclerosis-a-case-presentation-and-literature-review
#18
Murat Mert Atmaca, Candan Gurses
PURPOSE: To search the literature for the frequency, pathogenesis, prognosis, and treatment of seizures and status epilepticus (SE) in patients with multiple sclerosis (MS). METHODS: We report 2 patients with MS who presented with SE and review the literature. RESULTS: Seizures and SE episodes worsened during MS relapses in the first patient. SE episodes and MS relapses significantly decreased after initiation of natalizumab treatment but she still had seizures and was taking 4 antiepileptic drugs (AEDs)...
January 1, 2017: Clinical EEG and Neuroscience: Official Journal of the EEG and Clinical Neuroscience Society (ENCS)
https://www.readbyqxmd.com/read/29160038/endoplasmic-reticulum-in-health-and-disease-the-12th-international-calreticulin-workshop-delphi-greece
#19
REVIEW
Aristidis S Charonis, Marek Michalak, Jody Groenendyk, Luis B Agellon
Starting from 1994, every 2 years, an international workshop is organized focused on calreticulin and other endoplasmic reticulum chaperones. In 2017, the workshop took place at Delphi Greece. Participants from North and South America, Europe, Asia and Australia presented their recent data and discussed them extensively with their colleagues. Presentations dealt with structural aspects of calreticulin and calnexin, the role of Ca(2+) in cellular signalling and in autophagy, the endoplasmic reticulum stress and the unfolded protein response, the role of calreticulin in immune responses...
November 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29157398/new-advances-in-disease-modifying-therapies-for-relapsing-and-progressive-forms-of-multiple-sclerosis
#20
REVIEW
Angela Vidal-Jordana
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system in which inflammation, demyelination, and axonal loss occurs from early stages of the disease. It mainly affects people between 20 and 40 years old, with a female predominance. Treatment options have been increasingly growing in the past years and newer drugs, some with novel mechanisms of action, are being developed for treating patients with MS. There is an increasing interest in developing new drugs that will promote neuroprotection and/or myelin repair through different mechanisms of action that may target the most degenerative component of the disease...
February 2018: Neurologic Clinics
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