[Relapsing-remitting multiple sclerosis: clinical and immunological aspects of the pathology on the example of molecules Sema4D and CD72]. / Remittiruyushchii rasseyannyi skleroz: kliniko-immunologicheskie aspekty patologii na primere molekul Sema4D i CD72.

OBJECTIVE: To study the expression of Sema4D (CD100), receptor CD72 and a role of Sema4D-CD72-dependent signal in the control of the functions of immunocompetent cells in relapsing-remitting multiple sclerosis (RRMS). MATERIAL AND METHODS: We studied 76 patients, including 52 with RRMS (41 in remission and 11 in exacerbation), 35 women (67.3%) and 17 men (32.7%) aged 18-55 years, who did not receive disease-modifying drugs, and 24 healthy donors. A controlled clinical and immunological examination of patients with RRMS was carried out proving the involvement of the Sema4D molecule and its CD72 receptor in pathological reactions in this autoimmune disease. RESULTS AND CONCLUSION: The use of SemaD as a target in the treatment of RRMS is scientifically substantiated. In case of a positive decision on the use of anti-Sema4D drugs, it will be necessary to take into account the effects of semaphorin not only in the central nervous system, but also in the immune system of patients with RRMS.

[Factors regulating the activity of b-lymphocytes, as potential biomarkers of multiple sclerosis]. / Faktory, reguliruiushchie aktivnost' V-limfotsitov, kak potentsial'nye biomarkery rasseiannogo skleroza.

AIM: To assess the possibility of using serum levels of chemokine CXCL13, B-cell activating factor (BAFF), interleukin 1 and 17 (IL-10, IL-17) as markers of the development/progression of multiple sclerosis (MS). MATERIAL AND METHODS: Sixty-seven patients with MS in remission and 14 healthy volunteers were examined. The levels of BAFF, CXCL13 and the main products of Th17 and Treg - interleukin 17 (IL-17) and IL-10 in the serum were determined, their relationship with clinical characteristics of MS during remission was assessed. RESULTS AND CONCLUSION: The content of IL-17 and BAFF in the serum of patients with MS did not differ significantly from the control group, and the levels of IL-10 and CXCL13 were lower than the corresponding indicators of healthy donors. In patients with MS, no correlation was found between IL-17, IL-10, BAFF and clinical characteristics of MS. The level of CXCL13 correlated with quality of life, fatigue, clinical and functional status of patients. According to the results of this study, BAFF and CXCL13 cannot be proposed as diagnostic biomarkers of MS.

[The association of psychological gender characteristics with quality of life and clinical aspects in patients with multiple sclerosis]. / Sviaz' gendernykh osobennostei patsientov s rasseiannym sklerozom s kachestvom zhizni i klinicheskimi osobennostiami zabolevaniia.

AIM: To study the association between psychological gender characteristics and illness duration, severity of disability, asthenia, depression, anxiety and quality of life in multiple sclerosis (MS). MATERIAL AND METHODS: One hundred patients (62 females and 38 males) with multiple sclerosis were studied. The following methods were used: The Mini-Mental State Examination, The Bem Sex Role Inventory adapted in Russia, The Expanded Disability Status Scale, The Multidimensional Fatigue Inventory-20, The Beck Depression Inventory, The Spilberger State-Trait Anxiety Inventory, The Short Form-36 (The Life Quality Questionnaire). RESULTS AND CONCLUSION: The majority of patients had an androgynous type of psychological gender, some of patients were feminine. It was shown that there was an association between the number of feminine and masculine traits and MS duration, worsening of disability characteristics and life quality, increase in asthenia, depression and anxiety.

[Relapsing-remitting multiple sclerosis: clinical and immunological aspects of the pathology on the example Sema4D and CD72]. / Remittiruiushchii rasseiannyi skleroz: kliniko-immunologicheskie aspekty patologii na primere molekul Sema4D i CD72.

AIM: To explore the expression of Sema4D, CD72 receptor and a role of Sema4D-CD72 signal in the control of immunocompetent cell function in remitting-relapsing multiple sclerosis (RRMS). MATERIAL AND METHODS: Fifty-two patients with RRMS diagnosis according to 2010 revised McDonald's criteria were studied. The control group included 24 healthy people. A flow cytometry method was used to measure the expression of semaphorin Sema4D by T-lymphocytes of peripheral blood, expression of CD72 receptor by B-lymphocytes, percentage of cells containing pro- and anti-inflammatory cytokines. The level of soluble Sema4D (sSema4D) was evaluated by ELISA. RESULTS: The level of Sema4D expression on T-lymphocytes (Mean Fluorescence Intensity - MFI) prevailed in cell subpopulations in patients with RRMS compared with the control group. Characteristics of membrane and sSema4D correlate with clinical presentations of the autoimmune disease. An increase in sSema4D level during cell cultivation was identified in RRMS patients. The results show the involvement of Sema4D in the hyperactivation of B-cell-mediated immunity through CD72 receptor and induction of proinflammatory cytokine synthesis. CONCLUSION: RRMS is associated with elevated expression of Sema4D in the immune system. Membrane and sSema4D involved in the pathological process in RRMS. The authors suggest several mechanisms of the involvement of semaphorin and its receptor in the pathogenesis of RRMS: the direct damage of nervous tissues by sSema4D penetrated through the blood brain barrier disrupted in RRMS or by membrane Sema4D due to the infiltration of the central nervous system by T-lymphocytes and hyperactivation of B-cell-mediated immunity.

[The effect of psychological gender on adherence to immunomodulatory therapy in patients with multiple sclerosis]. / Vliianie gendera bol'nykh rasseiannym sklerozom na priverzhennost' immunomoduliruiushchei terapii.

AIM: To study the association between psychological gender and adherence to immunomodulatory therapy in patients with multiple sclerosis. MATERIAL AND METHODS: Thirty-four patients (25 women and 9 men) with the diagnosis of multiple sclerosis were examined. The following methods were used: MMSE, The Bem Sex Role Inventory adapted in Russia, Beck Depression Inventory, State-Trait Anxiety Inventory. During three months patients reported the first and the last immunomodulator injections dates from every new pack. Then the patients' self-reports systematization and analysis were performed, drug-taking compliance and timing compliance were calculated. RESULTS AND CONCLUSION: Twenty-eight patients had an androgynous type of psychological gender and six persons were feminine. The association was determined between high compliance and such psychological gender peculiarities as a significantly large number of feminine traits than masculine ones and the low number of masculine characteristics in men.

[Lipoprotein (a) in patients with carotid atherosclerosis]. / Lipoprotein (a) u bol'nykh s karotidnym aterosklerozom.

AIM: To evaluate the role of lipoprotein (a) in an atherosclerotic lesion of precerebral arteries and stroke development. MATERIAL AND METHODS: Thirty-eight patients with atherosclerotic lesions of the carotid arteries established by duplex scanning, including 28 post stroke patients and 10 patients with asymptomatic atherosclerosis, were examined. Lipoprotein (a) was determined by immunosorbent assay in the serum and supernatant after 3-day cultivation of neutrophils. RESULTS AND CONCLUSION: There was a correlation between serum lipoprotein (a) and endothelium-dependent vasodilation of the brachial artery, and the relationship of culture lipoprotein (a) with the severity of atherosclerotic lesions of precerebral arteries and prothrombin time. Thus, the effect of lipoprotein (a) on the atherogenesis may be mediated by endothelial dysfunction and the mechanism of realization of stroke development is prothrombogenic effects on hemostasis.

[Interferon-induced depression and peripheral blood serotonin in patients with multiple sclerosis]. / Interferon-indutsirovannaia depressiia i soderzhanie serotonina v perifericheskoi krovi u bol'nykh rasseiannym sklerozom.

AIM: To study the dynamics of anxiety-depressive disorders and peripheral blood serotonin in patients with multiple sclerosis (MS) during interferon-ß (IFN-ß) therapy. MATERIAL AND METHODS: The level of anxiety and depression in 227 MS patients was measured by psychometric testing at baseline and during treatment. The concentration of serotonin in serum of patients was determined by enzyme immunoassay. RESULTS: The presence of emotional disorders in patients with MS was confirmed. Their relationship with personality characteristics of the patient, the course of the disease and social status was shown. The level of humoral serotonin was lower in patients with MS. The relationship between the serotonergic system deficiency in patients with MS and anxiety disorders was shown. Interferon-induced depression was not associated with serotonin metabolism. It is a multifactor condition influenced by the patient's initial emotional level, personality characteristics, psychological reaction to therapy and the unfavorable dynamics of the disease. CONCLUSION: IFN-ß does not appear to induce depression in MS patients.

[Inflammatory mechanisms of fatigue syndrome in Parkinson's disease].

OBJECTIVE: To study clinical characteristics of fatigue syndrome in patients with Parkinson's disease (PD) and a role of inflammation in its development. MATERIAL AND METHODS: We examined 98 patients with confirmed diagnosis of PD and 18 healthy people. Clinical examination included an analysis of anamnesis and objective somatic symptoms. The unified Parkinson's disease rating scale, The Hoehn and Yahr scale, the Multidimensional Fatigue Inventory (MFI-20) scale, the Modified Fatigue Impact Scale (MFIS), the Hospital Anxiety and Depression Scale (HADS), The Epworth Sleepiness Scale (ESS), Vein's Autonomic Symptoms Questionnaire (VASQ) were used for quantitative assessment. Serum concentrations of IL-6 were measured in 65 patients and 18 controls using ELISA. RESULTS AND CONCLUSION: In PD patients, fatigue assessed with MFI-20 was recorded in 46 (47%) cases and fatigue as assessed with MFIS in 45 (46%) of cases. High frequency and severity of fatigue syndrome were observed. The most prominent components in the structure of fatigue were physical fatigue, reduced motivation and decreased activity. Signs of fatigue increased with disease progression. Correlation between fatigue and axial motor symptoms of PD is of interest. Patients had higher serum IL-6 levels compared to the controls. Concentrations of IL-6 were correlated with fatigue severity and its main components (general and physical fatigue, decreased activity) and with depression level.

[Additional methods of diagnosis of unstable atherosclerotic plaques in carotid arteries]. / Dopolnitel'nye metody diagnostiki nestabil'noi ateroskleroticheskoi bliashki v sonnykh arteriiakh.

The method of enzyme-linked immunosorbent assay (ELISA) was used to study the concentration of interleukins (OL)-6, 10, C-reactive protein (CRP) in blood serum of 61 patients presenting with atherosclerotic lesions of carotid arteries (CA). The obtained findings were compared with the morphological peculiarities of the biopsy materials of the atherosclerotic plaques (ASP) obtained while carrying out carotid endarterectomy (CEA). An increased concentration of IL-6 and CRP in blood serum of patients with unstable ASPs was revealed. It was shown that measuring cytokines and CRP in blood serum may be used as an additional method for diagnosis of unstable nature of ASP in the CAs in order to determine the indications for carotid endarterectomy.

Semaforin Sema4D in the immune system in multiple sclerosis.

The expression of class IV semaforin Sema4D and its CD72 receptor on lymphocytes was studied in patients with multiple sclerosis. The disease was associated with an increase in Sema4D level on intact T lymphocytes and with its more intense shedding from the membrane of activated cell. Multiple sclerosis was also associated with a decrease of CD72 receptor expression by B lymphocytes. Possible contribution of Sema4D to the disease development via the direct effects in the CNS and the immunomodulatory effect, specifically, B cell activity regulation, was discussed.

[A chronic fatigue syndrome and blood platelet serotonin levels in patients with multiple sclerosis]. / Sindrom khronicheskoi ustalosti u bol'nykh rasseiannym sklerozom i soderzhanie serotonina v trombotsitakh perifericheskoi krovi.

Sixty patients with multiple sclerosis and 12 healthy controls were examined. The fatigue was measured by the Fatigue Severity Scale (FSS). Concentration of platelet serotonin was analyzed with immunoassay techniques («Serotonin ELISA"). The results of the study have shown the primary role of fatigue in multiple sclerosis, with the prevalence of this syndrome reached 57.6%. The patients with multiple sclerosis had low concentration of platelet serotonin that was correlated with clinical features of the disease.

[Brain-derived and ciliary neurotrophic factors in patients with multiple sclerosis]. / Mozgovoi i tsiliarnyi neirotroficheskie faktory u bol'nykh rasseiannym sklerozom.

Objective. To study serum concentrations of BDNF and CNTF in patients with multiple sclerosis (MS) and compare them to clinical characteristics of MS. Material and methods. We examined 43 patients with confirmed diagnosis of MS according to McDonald's criteria with remitting type of disease course. Patients were in a stable condition and did not receive hormone treatment during the last 30 days. Serum concentrations of BDNF and CNTF were measured using ELISA. Results. Mean serum BDNF concentration was 7.9 (5.21; 14.7) ng/ml that was significantly lower (p=0.0001) compared to control values and was correlated with depression severity (r= -0.31, p=0.04) and physical asthenia (r= -0.32, p=0.04). CNTF concentration was 69.9 (31.2; 123.3) pg/ml (CNTF was not found in healthy people) and was correlated with the results of cognitive function assessment (the PASAT test) (r= -0.30, p=0.046). Conclusion. The difference in BDNF and CNTF serum concentrations between MS patients and healthy people and correlations with some clinical characteristics of MS provide evidence for the involvement of these factors in MS pathogenesis.

[The CD100 semaphorin expression on peripheral blood T-lymphocytes in patients with relapsing-remitting multiple sclerosis].

The expression of CD100 semaphorin by the intact peripheral blood T lymphocytes in multiple sclerosis (MS) has been studied. The level of middle florescence intensity (MFI) and the number of B-lymphocytes bearing CD72 were evaluated. There were significant differences in the level of CD100 in patients compared to healthy volunteers. These data suggest the use of semaphorin as a possible therapeutic target in pathological inflammation in MS.

[Mental disorders in senile age patients with cerebrovascular disease and postural instability].

The features of psychiatric disorders in senile cerebrovascular patients and their relationships with postural disorders were investigated. The dizziness and imbalance lead to social exclusion of patients, which contributes to emotional disorders, a frequent variant of which is depression (71 % of cases). A close correlation of anxious and depressive symptoms was received (59 % of cases). It was showed by computerized stabilometry that emotional disorders exacerbate existing imbalance, reflected in increasing of speed of the center of pressure, length and area of statokineziogramm.

[Leucocytes' ability to accumulate and secrete cholesterol is a nonspecific factor of immune inflammation in patients with atherothrombotic stroke].

The aim of the study was investigation of nonspecific inflammation markers in atherosclerotic injury of major arteries of the head (MAH). A complex study, including duplex ultrasonography, CT, measurement of cholesterol and its fractions, has been conducted in 85 patients with atherothrombotic (72 patients) and lacunar (23 patients) stroke. The ability of leucocytes' culture to accumulate and secrete cholesterol in vitro was studied as a nonspecific inflammatory marker of lesion of atherosclerotic MAH. A high level of this index was characteristic of atherothrombotic type of stroke comparing to lacunar stroke and the control group. Furthermore, high levels of this index correlated with severity of atherosclerotic injury of MAH, in particular with plaques. The dynamics of the index after 24-day therapy by statins (vasilip) is presented. We suppose that the protective influence of statins in patients after ischemic stroke may be caused by the effects on the level of immune competent cells including reducing leucocytes ability to accumulate and secrete protein-lipid complexes.

[Method for determining leukocytic lipid-releasing capacity in the diagnosis of mechanisms responsible for atherogenesis in patients with coronary heart disease and ischemic stroke].

The authors have studied the mechanism responsible for neutrophilic accumulation and release of protein-lipid complexes in patients with atherosclerosis and the clinical value of this reaction. They present the results of experimental studies and clinical observations in the groups of patients with ischemic stroke, coronary heart disease, bronchial asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis. Whether the process of neutrophilic and release of protein-lipid can be in vitro modulated in a 3-day culture has been demonstrated. The high diagnostic value of the method for determining the lipid-releasing capacity of leukocytes is shown. Some proteins involving in the formation of pathogenic protein-lipid complexes are identified. There is evidence for the use of new differential criteria for visceral diseases originating from atherosclerosis.

[Endothelium dysfunction in patients with ischemic stroke].

A vasomotor endothelial function has been studied in 57 patients with ischemic stroke using ultrasound by the reaction of the brachial artery to reactive hyperemia. The duplex scanning of brachyocephalic arteries was conducted. Twenty-four patients had impaired endothelial-dependent vasodilatation. Endothelial dysfunction was associated with cholesterol blood level and smoking. Aging, positive family history and arterial hypertension did not affect this parameter. A level of vasomotor dysfunction correlated with intima-media correlation, the presence of plaques in the carotid arteries and internal carotid artery occlusion. Impaired endothelial-dependent vascular relaxation occurred more frequently in atherothrombotic than in lacunar stroke and in patients with a severe brain damage.

[Changes in poststroke asthenia in the course of rehabilitation]. / Dinamika postinsul'tnoi astenii v protsesse vosstanovitel'nogo lecheniia.

Questionnaire (asthenia MFI) survey of 2043 patients early in rehabilitation after ischemic stroke in the territory of the carotid arteries was made. Asthenia was detected in 81% patients with elevated total score, physical, psychic asthenia, hypoactivity and low motivation. Asthenia was secondary and correlated with social maladaptation. Rehabilitation in a specialized neurological department of health resort Ust-Kachka leads to positive changes in the above indices.

[Multiple sclerosis: acute state or malignant course?]. / Rasseiannyi skleroz: ostrye formy ili zlokachestvennoe techenie?.

Multiple sclerosis (MS) which had developed in a 19-year-old female patient took a malignant course and terminated fatally three years after first symptoms. The case was characterized by an acute onset, seven severe exacerbations against combined pyramidal, cerebellar, visual, psychopathological and hyperkinetic disorders. The authors believe improper application of the term "acute" to rapid lethal outcome cases. In their opinion, they should be called cases of MS malignant course, the latter implying an unfavourable outcome of MS due to primarily truncal location of the demyelination process.