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  • 1
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 85, No. 19 ( 2015-11-10), p. 1727-1728
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
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  • 2
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 16, No. 4 ( 2010-04), p. 387-397
    Abstract: Lipoic acid is a natural anti-oxidant available as an oral supplement from a number of different manufacturers. Lipoic acid administered subcutaneously is an effective therapy for murine experimental autoimmune encephalomyelitis, a model of multiple sclerosis. The aim of this study was to compare serum lipoic acid levels with oral dosing in patients with multiple sclerosis with serum levels in mice receiving subcutaneous doses of lipoic acid. We performed serum pharmacokinetic studies in patients with multiple sclerosis after a single oral dose of 1200 mg lipoic acid. Patients received one of the three different racemic formulations randomly: tablet (Formulation A) and capsules (Formulations B and C). Mice pharmacokinetic studies were performed with three different subcutaneous doses (20, 50 and 100 mg/kg racemic lipoic acid). The pharmacokinetic parameters included Maximum Serum Concentrations (C max in μg/ml) and area under the curve 0—infinity (AUC 0—infinity in μg*min/ml). We found mean C max and AUC 0—infinity in patients with multiple sclerosis as follows: group A ( N = 7) 3.8 ± 2.6 and 443.1 ± 283.9; group B ( N = 8) 9.9 ± 4.5 and 745.2 ± 308.7 and group C ( N = 8) 10.3 ± 3.8 and 848.8 ± 360.5, respectively. Mean C max and AUC 0—infinity in the mice were: 100 mg/kg lipoic acid: 30.9 ± 2.9 and 998 ± 245; 50 mg/kg lipoic acid: 7.6 ± 1.4 and 223 ± 20; 20 mg/kg lipoic acid: 2.7 ± 0.7 and 119 ± 33. We conclude that patients taking 1200 mg of lipoic acid from two of the three oral formulations achieved serum C max and AUC levels comparable to that observed in mice receiving 50 mg/kg subcutaneous dose of lipoic acid, which is a highly therapeutic dose in experimental autoimmune encephalomyelitis. A dose of 1200 mg oral lipoic acid can achieve therapeutic serum levels in patients with multiple sclerosis.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2008225-3
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  • 3
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 8, No. 2 ( 2021-02), p. 456-470
    Abstract: To determine whether animals with Japanese macaque encephalomyelitis (JME), a spontaneous demyelinating disease similar to multiple sclerosis (MS), harbor myelin‐specific T cells in their central nervous system (CNS) and periphery. Methods Mononuclear cells (MNCs) from CNS lesions, cervical lymph nodes (LNs) and peripheral blood of Japanese macaques (JMs) with JME, and cervical LN and blood MNCs from healthy controls or animals with non‐JME conditions were analyzed for the presence of myelin‐specific T cells and changes in interleukin 17 (IL‐17) and interferon gamma (IFN γ ) expression. Results Demyelinating JME lesions contained CD4 + T cells and CD8 + T cells specific to myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and/or proteolipid protein (PLP). CD8 + T‐cell responses were absent in JME peripheral blood, and in age‐ and sex‐matched controls. However, CD4 + Th1 and Th17 responses were detected in JME peripheral blood versus controls. Cervical LN MNCs from eight of nine JME animals had CD3 + T cells specific for MOG, MBP, and PLP that were not detected in controls. Mapping myelin epitopes revealed a heterogeneity in responses among JME animals. Comparison of myelin antigen sequences with those of JM rhadinovirus (JMRV), which is found in JME lesions, identified six viral open reading frames (ORFs) with similarities to myelin antigen sequences. Overlapping peptides to these JMRV ORFs did not induce IFN γ responses. Interpretations JME possesses an immune‐mediated component that involves both CD4 + and CD8 + T cells specific for myelin antigens. JME may shed new light on inflammatory demyelinating disease pathogenesis linked to gamma‐herpesvirus infection.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2740696-9
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  • 4
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 167, No. 8 ( 2001-10-15), p. 4386-4395
    Abstract: Understanding the process of inducing T cell activation has been hampered by the complex interactions between APC and inflammatory Th1 cells. To dissociate Ag-specific signaling through the TCR from costimulatory signaling, rTCR ligands (RTL) containing the α1 and β1 domains of HLA-DR2b (DRA*0101:DRB1*1501) covalently linked with either the myelin basic protein peptide 85–99 (RTL303) or CABL-b3a2 (RTL311) peptides were constructed to provide a minimal ligand for peptide-specific TCRs. When incubated with peptide-specific Th1 cell clones in the absence of APC or costimulatory molecules, only the cognate RTL induced partial activation through the TCR. This partial activation included rapid TCR ζ-chain phosphorylation, calcium mobilization, and reduced extracellular signal-related kinase activity, as well as IL-10 production, but not proliferation or other obvious phenotypic changes. On restimulation with APC/peptide, the RTL-pretreated Th1 clones had reduced proliferation and secreted less IFN-γ; IL-10 production persisted. These findings reveal for the first time the rudimentary signaling pattern delivered by initial engagement of the external TCR interface, which is further supplemented by coactivation molecules. Activation with RTLs provides a novel strategy for generating autoantigen-specific bystander suppression useful for treatment of complex autoimmune diseases.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2001
    detail.hit.zdb_id: 1475085-5
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  • 5
    In: Journal of Neuroimaging, Wiley, Vol. 31, No. 6 ( 2021-11), p. 1111-1118
    Abstract: To compare transcapillary wall water exchange, a putative marker of cerebral metabolic health, in brain T 2 white matter (WM) lesions and normal appearing white and gray matter (NAWM and NAGM, respectively) in individuals with progressive multiple sclerosis (PMS) and healthy controls (HC). Methods Dynamic‐contrast‐enhanced 7T MRI data were obtained from 19 HC and 23 PMS participants. High‐resolution pharmacokinetic parametric maps representing tissue microvascular and microstructural properties were created by shutter‐speed (SS) paradigm modeling to obtain estimates of blood volume fraction (v b ), water molecule capillary efflux rate constant ( k po ), and the water capillary wall permeability surface area product ( P w S ≡ v b *k po ). Linear regression models were used to investigate differences in (i) k po and P w S between groups in NAWM and NAGM, and (ii) between WM lesions and NAWM in PMS. Results High‐resolution parametric maps were produced to visualize tissue classes and resolve individual WM lesions. Normal‐appearing gray matter k po and P w S were significantly decreased in PMS compared to HC ( p ≤ .01). Twenty‐one T 2 WM lesions were analyzed in 10 participants with PMS. k po was significantly decreased in WM lesions compared to PMS NAWM ( p 〈 .0001). Conclusions Transcapillary water exchange is reduced in PMS NAGM compared to HC and is further reduced in PMS WM lesions, suggesting pathologically impaired brain metabolism. k po provides a sensitive measure of cerebral metabolic activity and/or coupling, and can be mapped at higher spatial resolution than conventional imaging techniques assessing metabolic activity.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2035400-9
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  • 6
    In: Neurochemical Pathology, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 1986-2), p. 1-9
    Type of Medium: Online Resource
    ISSN: 0734-600X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1986
    detail.hit.zdb_id: 2428982-6
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  • 7
    Online Resource
    Online Resource
    Consortium of Multiple Sclerosis Centers ; 2022
    In:  International Journal of MS Care Vol. 24, No. 2 ( 2022-03-01), p. 90-97
    In: International Journal of MS Care, Consortium of Multiple Sclerosis Centers, Vol. 24, No. 2 ( 2022-03-01), p. 90-97
    Abstract: Activity Available Online: To access the article and evaluation online, go to https://www.highmarksce.com/mscare. Target Audience: The target audience for this activity is physicians, advanced practice clinicians, nursing professionals, pharmacists, and other health care providers involved in the management of patients with multiple sclerosis (MS). Learning Objectives: Recognize the frequency of utilization of non-DMT medications by MS patients and integrate questions about their use into patient history. Characterize and be mindful of the out-of-pocket cost burden of DMT and non-DMT medication use in patients with MS. Accreditation Statement: In support of improving patient care, this activity has been planned and implemented by The Consortium of Multiple Sclerosis Centers (CMSC) and Intellisphere, LLC. CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the health care team. This activity was planned by and for the health care team, and learners will receive 0.5 Interprofessional Continuing Education (IPCE) credit for learning and change. For Physicians: The Consortium of Multiple Sclerosis Centers designates this journal-based activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. For Nurses: This activity is awarded 0.5 contact hours of nursing continuing professional development (NCPD) (0.5 of these credits are in the area of pharmacology). For Pharmacists: This knowledge-based activity (UAN JA4008165-9999-22-020-H01-P) qualifies for 0.5 contact hours (0.05 CEUs) of continuing pharmacy education credit. For Physician Assistants: The Consortium of Multiple Sclerosis Centers has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.5 AAPA Category 1 CME credits. Approval is valid until April 1, 2023. PAs should only claim credit commensurate with the extent of their participation. It is the policy of the Consortium of Multiple Sclerosis Centers to mitigate all relevant financial disclosures from planners, faculty, and other persons that can affect the content of this CE activity. For this activity, all relevant disclosures have been mitigated. Disclosures: Francois Bethoux, MD, editor in chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has disclosed no relevant financial relationships. Alissa Mary Willis, MD, Associate Editor of IJMSC, has disclosed no relevant financial relationships. Daniel Hartung, PharmD, MPH, consults for the National Multiple Sclerosis Society and Sandoz Pharmaceuticals. Leorah Freeman, MD, PhD, has served as a consultant for Genentech, Celgene/Bristol Myers Squibb, EMD Serono, TG Therapeutics, and Novartis; and has received grant/program support from EMD Serono and Genentech. The staff at IJMSC, CMSC, and Intellisphere, LLC who are in a position to influence content have disclosed no relevant financial relationships. Laurie Scudder, DNP, NP, Continuing Education Director CMSC, has served as a planner and reviewer for this activity. She has disclosed no relevant financial relationships. Method of Participation: Release Date: April 1, 2022; Valid for Credit through: April 1, 2023 In order to receive CE credit, participants must: (1) Review the continuing education information, including learning objectives and author disclosures.(2) Study the educational content.(3) Complete the evaluation, which is available at https://www.highmarksce.com/mscare. Statements of Credit are awarded upon successful completion of the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. The CMSC and Intellisphere, LLC do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the CMSC or Intellisphere, LLC. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health care professionals without first evaluating their patients’ conditions, considering possible contraindications or risks, reviewing any applicable manufacturer’s product information, and comparing any therapeutic approach with the recommendations of other authorities.
    Type of Medium: Online Resource
    ISSN: 1537-2073
    Language: English
    Publisher: Consortium of Multiple Sclerosis Centers
    Publication Date: 2022
    detail.hit.zdb_id: 2128700-4
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology: Clinical Practice Vol. 11, No. 4 ( 2021-08), p. 298-303
    In: Neurology: Clinical Practice, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 4 ( 2021-08), p. 298-303
    Abstract: To determine whether closing the Part D coverage gap (donut hole) between 2010 and 2019 lowered patients' out-of-pocket costs for disease-modifying therapies (DMTs) for multiple sclerosis (MS). Methods Using nationwide Medicare Formulary and Drug Pricing Files, we analyzed Part D drug benefit design and DMT prices in 2010, 2016, and 2019. We calculated average monthly list prices for DMTs available in each year (4 DMTs in 2010, 11 DMTs in 2016, and 14 DMTs in 2019). We projected patients' annual out-of-pocket cost for each DMT alone under a standard Part D plan in that year. We estimated potential savings attributable to closing the coverage gap between 2010 and 2019 (beneficiaries' cost sharing dropped from 100% to 25%) under 3 scenarios: no increase in price, an inflation-indexed price increase (3% annually), and the observed price increase. Results Median monthly DMT prices rose from $2,804 to $5,987 to $7,009 over the years 2010, 2016, and 2019, respectively. Median projected annual out-of-pocket costs rose from $5,916 to $6,229 to $6,618. With unchanged or inflation-indexed DMT price changes, closing the coverage gap would have reduced annual out-of-pocket costs by $2,260 (38% reduction) and $1,744 (29% reduction), respectively. Despite having the lowest monthly price, generic glatiramer acetate had among the highest out-of-pocket costs ($6,731 to $6,939 a year) in 2019. Conclusions Medicare Part D beneficiaries can pay thousands of dollars yearly out of pocket for DMTs. Closing the Part D coverage gap did not reduce out-of-pocket costs for patients because of simultaneous increases in DMT prices.
    Type of Medium: Online Resource
    ISSN: 2163-0402 , 2163-0933
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2645818-4
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  • 9
    In: Immunology & Cell Biology, Wiley, Vol. 76, No. 1 ( 1998-02), p. 83-90
    Abstract: Immunization of Lewis rats with guinea‐pig myelin basic protein (Gp‐MBP) induced T cell responses to primary and secondary encephalitogenic determinants, as well as to a third non‐encephalitogenic epitope, residues 55–69. This sequence is of interest due to its protective activity against experimental autoimmune encephalomyelitis. Protection involved induction of MBP‐55–69‐specific T cells expressing cross‐reactive TCR BV8S6 genes that activated regulatory T cells specific for TCR BV8S2 determinants expressed on encephalitogenic T cells. We here present and discuss new evidence suggesting a possible immunological cross‐reactivity between the protective Gp‐MBP‐55–69 peptide and the regulatory BV8S2‐39–59 peptide. This cross‐reactivity, which may also occur between the human MBP‐55–74 peptide and the BV12S2‐38–58 sequence, has potentially important implications for human diseases such as multiple sclerosis.
    Type of Medium: Online Resource
    ISSN: 0818-9641 , 1440-1711
    Language: English
    Publisher: Wiley
    Publication Date: 1998
    detail.hit.zdb_id: 2011707-3
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  American Journal of Physical Medicine & Rehabilitation Vol. 101, No. 4 ( 2022-4), p. 405-409
    In: American Journal of Physical Medicine & Rehabilitation, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 4 ( 2022-4), p. 405-409
    Abstract: Fatigue is one of the most common and disabling symptoms of multiple sclerosis. A recent randomized controlled trial comparing a fatigue self-management program and a general multiple sclerosis education program found that both programs improved fatigue in participants with multiple sclerosis. Participants were randomized to a self-management program (fatigue: take control, n = 109) or a multiple sclerosis education program (multiple sclerosis: take control, n = 109). This secondary analysis of that trial used multilevel moderation analysis to examine moderators of treatment-related effects on fatigue (Modified Fatigue Impact Scale) from baseline through the 6-mo follow-up. The following potential treatment moderators were examined: age, sex, cohabitation/marital status, and baseline levels of self-efficacy, depression symptoms, and sleep quality. Cohabitation status (living with or without a spouse/partner) interacted with intervention group and time to predict fatigue impact ( P = 0.04). Fatigue: take control participants who lived with a spouse/partner showed a marginal effect in greater rate of improvement in fatigue compared with those who lived alone ( P = 0.08). However, rates of improvement in fatigue in multiple sclerosis: take control participants were similar in those living with or without a spouse/partner. These findings suggest that living with a spouse or partner may facilitate benefit from self-management interventions for multiple sclerosis–related fatigue. Future research should investigate the contribution of supportive others in self-management of fatigue in multiple sclerosis.
    Type of Medium: Online Resource
    ISSN: 1537-7385 , 0894-9115
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2272463-1
    detail.hit.zdb_id: 2049617-5
    SSG: 31
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