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Copyright of Ergoscience is the property of Schulz-Kirchner Verlag Gmbh and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zentralblatt fuer Arbeitsmedizin, Arbeitsschutz und Ergonomie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force 'Provision Structures and Therapeutics' summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated. [ABSTRACT FROM AUTHOR]

Pegylation of pharmacological substances was developed in the 1970s as a way of improving their efficacy and elimination and hence reducing the dosage frequency. A prominent example is pegylation of IFNα, which revolutionized the treatment of virus hepatitis in the late 1990s. Efforts have now succeeded in producing a pegylated interferon beta (PEG-IFN-β) to treat multiple sclerosis (MS) and the efficacy and safety have been investigated in a phase III trial called the ADVANCE study. The 1-year results of this randomized, double blind, multicenter, placebo-controlled study in more than 1500 MS patients show that administration of subcutaneous PEG-IFN-β significantly reduces the annual relapse rate and disability progression. The safety and tolerability profile of PEG-IFN-β was found to be similar to that of conventional IFN-β drugs. The most common adverse events were flu-like symptoms and redness at the injection site. The results of this study underscore that PEG-IFN-β is an interesting new therapeutic option in the treatment of relapsing-remitting MS that combines highly effective interferon with the established tolerability and safety profile of IFN-β at a reduced dosage frequency. [ABSTRACT FROM AUTHOR]

The immunotherapy of multiple sclerosis (MS) is currently one of the most dynamic fields in clinical neurology. The comprehensive number of well-established and new innovative treatment options are a challenge for an intensive preoccupation with the differential indications and an activity-driven treatment control. In this context this review summarizes the known predictors of the natural course of MS and gives a review of challenges to be expected in association with predictors of treatment control. [ABSTRACT FROM AUTHOR]

Although there is still no cure for Multiple Sclerosis (MS), effective strategies are available to modify the disease course, to treat relapses, to manage symptoms, to improve functions, and to provide emotional support. In combination, these treatments enhance the quality of life for people living with MS. [ABSTRACT FROM AUTHOR]

The introduction of interferon-β in 1993 in the USA and 2 years later in Europe made it possible for the first time to alter the course of the disease in patients with relapsing-remitting multiple sclerosis (MS). Subsequently, interferon-β was approved for the treatment of patients with active secondary progressive MS (1999) and early relapsing-remitting MS following a first demyelinating event (clinically isolated syndrome, CIS) (2006). Here we provide an overview of the clinical experience gathered during more than 20 years of interferon-β use focusing on long-term efficacy and safety and the impact of early initiation of treatment. Furthermore, the following aspects will be discussed: putative mechanisms of action of interferon-β, indications for a disease-modifying therapy, clinical relevance of neutralizing antibodies, importance of adherence in MS therapy, high versus low frequency therapy, combination therapies with interferon-β and safety of interferon-β in children and adolescents with MS and during pregnancy. [ABSTRACT FROM AUTHOR]

Interferon beta and glatiramer acetate are still considered to be the first-line therapeutics for treatment of relapsing forms of multiple sclerosis (MS). The use of new compounds, such as natalizumab or fingolimod, is restricted to severe forms of relapsing MS or cases refractory to first-line treatment owing to substance-specific risk-benefit considerations. Teriflunomide is a new compound which has recently been approved as a first-line treatment of relapsing forms of MS in the USA and Australia. It is characterized by a once daily oral administration and a comparably well-established long-term safety profile. The main therapeutic effect is considered to be mediated via the inhibition of the de novo synthesis of pyrimidine in proliferating immune cells. The pro-drug of teriflunomide, leflunomide, has a label for treating rheumatoid arthritis (RA) for many years. Two recently published phase III clinical trials (TEMSO, TOWER) tested teriflunomide in patients with relapsing forms of MS and efficacy was demonstrated, with positive effects on relapse rates and disease progression using 14 mg/day. Overall, the safety profile in these studies was favorable as expected from experiences with leflunomide in RA. In patients treated with teriflunomide regular monitoring of blood cell counts and liver enzymes is required. Teriflunomide must not be used during pregnancy. In this article the recent phase II and phase III clinical trial data are reviewed and the potential of teriflunomide for the treatment of relapsing forms of MS is discussed. [ABSTRACT FROM AUTHOR]

Curcumin and Multiple Sclerosis In Multiple Sclerosis (MS), the inflammation caused by the patient's own immune system against the central nervous tissue leads to progressive loss of neurological functions. Reactive oxygenated species and nitric oxid, the latter produced by nitric oxid-Synthases (NO) destroy axons and myelin sheets. In experimental autoimmune encephalomyelitis (EAE), an animal model for MS, arginase I expression is upregulated and an inhibition of arginase helps to delay the onset of EAE-symptoms. Since arginases compete with NO for the substrate arginine, a complex network regulates NO activity. The prevalence of MS in societies, where curcumin is part of the daily diet, is lower than in the northern hemisphere. A specific inhibition of arginases by curcuma extract in vitro and evidence for a direct association of compounds therein with arginases suggests a perspective for the treatment of MS. [ABSTRACT FROM AUTHOR]

Background: In order to meet the needs of therapy of multiple sclerosis (MS) new immune therapies with a user-friendly application and better effectiveness together with good tolerability are necessary. Compassionate use: With respect to its potential to improve MS therapy, patients with a high medical need were given access to Fingolimod even before marketing approval. Therefore, a compassionate use program unique in the field of MS was initiated. In total 137 centers participated (75 % outpatient neurologists and 25 % hospitals). Within 19 weeks 135 patients were enrolled to receive Fingolimod. The patients in the compassionate use program can be representatively described as showing hardly controllable disease activity and progression with currently available, often poorly tolerated therapy. The compassionate use program for these patients offered better control of the disease with Fingolimod. The adverse events were as expected. Conclusions: The Fingolimod compassionate use program demonstrated the need for this new therapeutic option. Patients who were not yet sufficiently treated were provided with an effective therapy with a good safety profile and a user-friendly administration form. [ABSTRACT FROM AUTHOR]

Copyright of Musiktherapeutische Umschau is the property of Vandenhoeck & Ruprecht GmbH & Co. KG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Due to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ion channel modulators (e. g. pregabalin, gabapentin, carbamazepine). The aim of this study was to investigate the use of these drugs in clinical practice in a larger patient cohort. Patients: Data from 533 MS patients [439 without and 94 patients with add-on therapy (treatment group)] were evaluated retrospectively. All patients received a detailed neurological examination including evaluation of EDSS scores. Results: Pregabalin and gabapentin are used most commonly. Abnormal sensations are the most frequent reason for therapy initiation. Patients with higher EDSS values and/or under mitoxantrone treatment most frequently receive additional therapy. Conclusion: So far, it is not known whether the investigated agents exert a beneficial influence on the disease course of MS itself beyond a mere symptomatic treatment. Further research efforts and clinical studies are necessary to address this question. [ABSTRACT FROM AUTHOR]

zathioprine (AZA) is a purine analogue which has been used in the treatment of multiple sclerosis (MS) for over 30 years. After the approval of immunomodulatory drugs, such as recombinant interferon beta and glatiramer acetate, AZA now only plays a minor role in MS therapy. The results of a recently published phase III trial (CLARITY trial) involving an oral formulation of the purine analogue cladribine, a substance which is at least structurally related to AZA, may soon lead to the approval of cladribine tablets as a new oral MS therapeutic. The following overview provides a comparison of the mode of action, side-effect profile and data currently available on AZA and cladribine in the treatment of MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system in which autoreactive CD4+ and CD8 + T lymphocytes, B lymphocytes, macrophages, antibodies, and cytokines attack the myelin sheaths and damage the axons. The basic therapeutic agents and disease-modifying drugs that are currently available for MS require regular and frequent parenteral administration and therefore long-term compliance is unsatisfactory. Among all of the new oral MS agents presently under development, cladribine is the only substance that appears able to achieve long treatment-free intervals after only short-term administration. Cladribine is an immunomodulator with a long-lasting effect and a well-characterized safety profile based on over 15 years of experience with the parenteral route for MS and other indications. This contribution addresses the need for novel MS treatment approaches to improve compliance and describes the mechanism of action of cladribine, the available data on effectivity and safety, and the clinical development of the oral formulation of cladribine. The results from the recently published 96-week, double-blind, randomized, placebo-controlled, multicenter study CLARITY (CLAdRIbine Tablets Treating MS Oral-IY) are very promising. They clearly show that oral cladribine reduces relapse rate, disability progression and disease activity and burden as evidenced by MRI. [ABSTRACT FROM AUTHOR]

Mobility limitation is a frequent clinical symptom of multiple sclerosis (MS) that poses a therapeutic challenge. For years results of animal experiments and clinical experience have indicated that the potassium channel blocker 4-aminopyridine improves axonal excitatory circuits and thus muscular strength in demyelinating diseases. A recently conducted randomized, placebo-controlled, multi-center phase 3 clinical trial in MS patients was able to show that an oral sustained-release formulation of 4-aminopyridine (Fampridine-SR) represents a suitable agent for treatment of walking disability in MS patients. This overview presents the study data and discusses the value of 4-aminopyridine for the symptomatic treatment of MS as a neurofunctional modifier of this disabling disease. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) has traditionally been considered to be a T cell-mediated disease. However, there is an increasing body of evidence for the involvement of B cells and autoantibodies in the pathology of this disease, providing a rationale for treatment strategies directed against B cells. This paper summarizes the evidence for a key role of B cells in the immunopathology of MS and reviews data supporting the use of a novel B cell-targeted therapy, atacicept, for this condition. Atacicept is a human recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B cell maturation, function and survival. Atacicept has shown selective effects on cells of the B cell lineage, acting on mature B cells and blocking plasma cells and late stages of B cell development while sparing B cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated. Ongoing clinical studies are investigating the safety, tolerability and efficacy of atacicept in patients with MS, SLE and RA. [ABSTRACT FROM AUTHOR]

In MS patients with contraindications, intolerance, or failure of established immunomodulatory drugs, intravenous immunoglobulins (IVIG) are increasingly being administered. Several clinical studies recently showed that IVIG are generally safe, well tolerated and only occasionally have serious side effects. While some studies indicated beneficial effects from IVIG in relapsing-remitting MS, the recently published PRIVIG study failed to show any clinical benefit. Although pregnancy and the post-partum period appear to be interesting potential indications for IVIG, since under those conditions all other immunomodulatory drugs except for corticosteroids are not indicated, there are no data from adequate studies to support the use of IVIG in this patient group. For other indications in MS patients, study results are either negative or lacking. Overall IVIG may be considered a safe second-line compound in patients with relapsing-remitting MS. However, efficacy, long-term consequences, and optimal dosage of IVIG have not been unequivocally ascertained as yet. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies are of growing interest as treatment options for immune-mediated diseases in neurology. As our knowledge of immunological principals increases, we learn to modulate specifically mechanisms of pathogenesis by the use of monoclonal antibodies. It is clearly desirable to improve efficacy in disease treatment without increasing toxicity by using drugs with more specific modes of action. Natalizumab was the first monoclonal antibody approved in the field of neurology for treatment of relapsing remitting multiple sclerosis (MS). Several other monoclonal antibodies are currently under investigation. Alemtuzumab, a monoclonal antibody targeting CD52, is a highly promising agent currently being studied in two phase III clinical trials. In this review, data from the recently published phase II clinical trial in the treatment of early relapsing remitting MS is summarized and analyzed in light of the development of alemtuzumab for MS and its potential role in treating this disease is discussed. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Komplementaere und Integrative Medizin is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this article recent advances in research on the pathogenesis of multiple sclerosis (MS) are summarized. New evidence from molecular histopathology is discussed focussing on neurodegenerative aspects. In addition findings with a direct effect on therapeutic decisions are presented which have contributed to improved immunotherapy. During the last decade important advances in immunotherapy have proven especially useful for patients with relapsing-remitting MS. Escalating algorithms are available for both relapses and long-term immunotherapy. Novel therapeutic approaches with monoclonal antibodies have increasing importance, yet side effects are not completely understood. The pathogenetic insights presented here may open new avenues for novel immunotherapies and lead to individualized MS therapy in the future. Limitations are given for primary progressive MS due to the lack of suitable tissue specimens and experimental models. Neuroprotective treatment strategies aiming at the protection of glial and neuronal cells are still in early stages of development. [ABSTRACT FROM AUTHOR]

The publication of the 2012/2013 edition of an informational guide by the Deutsche Multiple Sklerose Gesellschaft (German Multiple Sclerosis Society, DMSG) on the symptoms and treatments of multiple sclerosis is announced.