Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by chronic brain inflammation. Leukocyte infiltration of brain tissue causes inflammation, demyelination, and the subsequent formation of sclerotic plaques, which are a hallmark of MS. Activation of proinflammatory cytokines is essential for regulation of lymphocyte migration across the blood–brain barrier. We demonstrate increased levels of many cytokines, including IL-2RA, CCL5, CCL11, MIF, CXCL1, CXCL10, IFNγ, SCF, and TRAIL, were upregulated in cerebrospinal fluid (CSF), whereas IL-17, CCL2, CCL3, CCL4, and IL-12(p40) were activated in MS serum. Interaction analysis of cytokines in CSF demonstrated a connection between IFNγ and CCL5 as well as MIF. Many cells can contribute to production of these cytokines including CD8 and Th1 lymphocytes and astrocytes. Therefore, we suggest that IFNγ released by Th1 lymphocytes can activate astrocytes, which then produce chemoattractants, including CCL5 and MIF. These chemokines promote an inflammatory milieu and interact with multiple chemokines including CCL27 and CXCL1. Of special note, upregulation of CCL27 was found in CSF of MS cases. This observation is the first to demonstrate CCL27 as a potential contributor of brain pathology in MS. Our data suggest that CCL27 may be involved in activation and migration of autoreactive encephalitogenic immune effectors in the brain. Further, our data support the role of Th1 lymphocytes in the pathogenesis of brain inflammation in MS, with several cytokines playing a central role.

Multiple sclerosis (MS) is a chronic debilitating inflammatory disease of unknown ethology targeting the central nervous system (CNS). MS has a polysymptomatic onset and is usually first diagnosed between the ages of 20–40 years. The pathology of the disease is characterized by immune mediated demyelination in the CNS. Although there is no clinical finding unique to MS, characteristic symptoms include sensory symptoms visual and motor impairment. No definitive trigger for the development of MS has been identified but large-scale population studies have described several epidemiological risk factors for the disease. This list is a confusing one including latitude, vitamin D (vitD) levels, genetics, infection with Epstein Barr Virus (EBV) and endogenous retrovirus (ERV) reactivation. This review will look at the evidence for each of these and the potential links between these disparate risk factors and the known molecular disease pathogenesis to describe potential hypotheses for the triggering of MS pathology.

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and consequent neuron injury. Although the pathogenesis of MS is largely unknown, a breach in immune self-tolerance to myelin followed by development of autoreactive encephalitogenic T cells is suggested to play the central role. The myelin basic protein (MBP) is believed to be one of the main targets for autoreactive lymphocytes. Recently, immunodominant MBP peptides encapsulated into the mannosylated liposomes, referred as Xemys, were shown to suppress development of experimental autoimmune encephalomyelitis, a rodent model of MS, and furthermore passed the initial stage of clinical trials. Here, we investigated the role of individual polypeptide components [MBP peptides 46–62 (GH17), 124–139 (GK16), and 147–170 (QR24)] of this liposomal peptide therapeutic in cytokine release and activation of immune cells from MS patients and healthy donors. The overall effects were assessed using peripheral blood mononuclear cells (PBMCs), whereas alterations in antigen-presenting capacities were studied utilizing plasmacytoid dendritic cells (pDCs). Among three MBP-immunodominant peptides, QR24 and GK16 activated leukocytes, while GH17 was characterized by an immunosuppressive effect. Peptides QR24 and GK16 upregulated CD4 over CD8 T cells and induced proliferation of CD25+ cells, whereas GH17 decreased the CD4/CD8 T cell ratio and had limited effects on CD25+ T cells. Accordingly, components of liposomal peptide therapeutic differed in upregulation of cytokines upon addition to PBMCs and pDCs. Peptide QR24 was evidently more effective in upregulation of pro-inflammatory cytokines, whereas GH17 significantly increased production of IL-10 through treated cells. Altogether, these data suggest a complexity of action of the liposomal peptide therapeutic that does not seem to involve simple helper T cells (Th)-shift but rather the rebalancing of the immune system.

Цель исследования. Доказательство сходной эффективности препарата тимексон (BCD-063, глатирамера ацетат производства ЗАо «БиоКАД», россия) и копаксон-тева («Тева» фармацевтическое предприятие лТД, израиль) у пациентов с ремиттирующим рассеянным склерозом. Материал и методы. В многоцентровое двойное слепое плацебоконтролируемое сравнительное рандомизированное исследование iii фазы были включены 158 пациентов с достоверным диагнозом ремиттирующего рассеянного склероза. рандомизация в группы BCD-063, копаксон-тева и плацебо производилась в соотношении 2:2:1 соответственно. Результаты и заключение. При анализе эффективности после 48 недель терапии было установлено отсутствие различий между группами BCD-063 и копаксон-тева как на основании показателей МрТ, так и по частоте обострений заболевания. По результатам оценки первичной конечной точки (количества МрТ-подтвержденных обострений на пациента в год) среднее количество обострений в группе BCD-063 составило 0,098361 (0,351422), в группе копаксон-тева-0,098361 (0,351422), в группе плацебо-0,178571 (0,390021). результаты оценки по шкалам ЕDSS, MSfC также показали отсутствие различий между группой BCD-063 и группой препарата копаксон-тева. Был установлен благоприятный профиль безопасности как препарата BCD-063, так и копаксон-тева. Полученные данные свидетельствуют о терапевтической эквивалентности препарата BCD-063 (ЗАо «БиоКАД», россия) и препарата копаксон-тева, что является важным аспектом для дальнейшего внедрения воспроизведенного препарата глатирамера ацетата в практику лечения рассеянного склероза. Ключевые слова: ремиттирующий рассеянный склероз, глатирамера ацетат, BCD-063, тимексон. Comparative, placebo-controlled clinical study of efficacy and safety of glatiramer acetate 20 mg in patients with relapsing-remitting multiple sclerosis: results of the first year of the study

No abstract

Five main variants of tremor were identified: distal postural and postural-intention (variant 1), distal intention (variant 2), proximal and distal intention and postural-intention (variant 3), Holmes (variant 4), axial (variant 5). Postural tremor (variants 1, 3) and rest tremor (variant 4) are caused by the central oscillators. Intention tremor (variants 2, 3), postural-intention tremor (variant 4), axial (variant 5) are caused by the pathology of cerebellar feedback loops. Clarification of mechanisms for the development of tremor in MS allowed to develop a scheme of differential treatment.

Addition of neuromultivit to basic therapy increased the efficacy of treatment of VR L5-S1.

No abstract