[Ofatumumab - a new drug for the treatment of multiple sclerosis]. / Ofatumumab ­ novyi preparat dlya lecheniya rasseyannogo skleroza.

Recently anti-B-cell therapy has been increasingly integrated into the treatment of multiple sclerosis (MS). This review is devoted to ofatumumab, a new drug of this line. Ofatumumab, an all-human monoclonal antibody used to treat chronic leukemia, binds to a different region than the binding site of other CD20 antibodies, including both a small and large loop in the CD20 receptor structure. This monoclonal antibody provides favorable results for MS by reducing the frequency of exacerbations and the risk of disability progression, significantly more pronounced when compared with teriflunomide. The drug can be used in patients with active relapsing MS and SPMS with exacerbations, with the ineffectiveness of first-line drugs as one of the options for second-line therapy, in patients with highly active MS, especially with a high risk of PML (transfer from natalizumab), as well as if there are difficulties in organizing intravenous courses in day hospitals (produced as outpatient injections).

[Treatment of multiple sclerosis with glatiramer acetate: a new look]. / Lechenie rasseyannogo skleroza preparatami glatiramera atsetat ­ novyi vzglyad.

In recent years, the use of a new dosage (40 mg) of glatiramer acetate (GA), which is administered 3 times weekly has become widespread. In Russia, the drug Timexon (produced by the company BIOCAD) was developed and passed successful clinical trials. The final efficacy analysis included 150 patients treated for 12 months. The convenience of using a double dose of GA in 40 mg, which is registered on the territory of the Russian Federation by two manufacturing companies: CJSC BIOCAD and Teva Pharmaceutical Enterprises Ltd., has been proven.

[Clinical cases of multiple sclerosis in children with cerebral palsy]. / Klinicheskie sluchai rasseiannogo skleroza u detei s detskim tserebral'nym paralichom.

The careful differential diagnosis is very important in pediatric cases of multiple sclerosis (MS). It has special difficulties, if MS started in patients with residual neurological pathology. Two cases of development of MS in children with cerebral palsy (CP) are presented. The clinical features and diagnostic difficulties in such comorbid situations are discussed .

[The risk of ischemic stroke in patients with multiple sclerosis]. / Risk razvitiia ishemicheskogo insul'ta u bol'nykh rasseiannym sklerozom.

A brief literature review on risk factors of ischemic stroke in patients with multiple sclerosis (MS) is presented. A case of ischemic stroke in a MS patient was demonstrated, and risk factors were identified.

Detection and quantification of epithelial progenitor cell populations in human healthy and IPF lungs.

BACKGROUND: In the human lung, epithelial progenitor cells in the airways give rise to the differentiated pseudostratified airway epithelium. In mice, emerging evidence confers a progenitor function to cytokeratin 5 (KRT5(+)) or cytokeratin 14 (KRT14(+))-positive basal cells of the airway epithelium. Little is known, however, about the distribution of progenitor subpopulations in the human lung, particularly about aberrant epithelial differentiation in lung disease, such as idiopathic pulmonary fibrosis (IPF). METHODS: Here, we used multi-color immunofluorescence analysis to detect and quantify the distribution of airway epithelial progenitor subpopulations in human lungs obtained from healthy donors or IPF patients. RESULTS: In lungs from both, healthy donors and IPF patients, we detected KRT5(+)KRT14(-), KRT5(-)KRT14(+) and KRT5(+)KRT14(+) populations in the proximal airways. KRT14(+) cells, however, were absent in the distal airways of healthy lungs. In IPF, we detected a dramatic increase in the amount of KRT5(+) cells and the emergence of a frequent KRT5(+)KRT14(+) epithelial population, in particular in distal airways and alveolar regions. While the KRT14(-) progenitor population exhibited signs of proper epithelial differentiation, as evidenced by co-staining with pro-SPC, aquaporin 5, CC10, or MUC5B, the KRT14(+) cell population did not co-stain with bronchial/alveolar differentiation markers in IPF. CONCLUSIONS: We provide, for the first time, a quantitative profile of the distribution of epithelial progenitor populations in human lungs. We show compelling evidence for dysregulation and aberrant differentiation of these populations in IPF.

[Effects of ecological characteristics of place of residence on the incidence, prevalence and risk of multiple sclerosis in the Republic North Ossetia - Alania]. / Ékologicheskie kharakteristiki mesta prozhivaniia i risk razvitiia rasseiannogo skleroza v Respublike Severnaia Osetiia - Alaniia.

Objective. To study the relationship between characteristics of place of residence and epidemiological indicators of multiple sclerosis (MS) in the Republic North Ossetia - Alania. Material and methods. We present the data on the effects of environmental characteristics of place of residence on the incidence, prevalence and risk of MS. Data of 110 MS patients and matched controls have been analyzed. Results. Ecological characteristics of place of residence of MS patients differ significantly from those of controls. The prevalence and incidence of MS increase in patients who have moved from presumably pollution free areas to the places with high population density and plant facilities. Conclusion. MS is thought to be a disease caused by the interaction of genetic susceptibility and environmental factors. Risk factors are intoxication with heavy metal and chemical compounds and living in environmentally disadvantaged areas.

[An analysis of an effect of infectious diseases and diet factors on the risk of multiple sclerosis in the population of the Republic North Ossetia - Alania]. / Analiz vliianiia nekotorykh vneshnikh faktorov na risk razvitiia rasseiannogo skleroza v populiatsii Respubliki Severnaia Osetiia - Alaniia.

Objective. To carry out the first in the Republic North Ossetia - Alania clinical epidemiological study of environmental risk factors for multiple sclerosis (MS) in the indigenous population. Material and methods. We have analyzed results of a questionnaire survey of 110 patients with MS and 110 matched controls. Results. We have identified statistically significant differences between the type of diet of MS patients and controls in different age periods, as well as the most significant infectious risk factors for MS. Conclusion. MS is a chronic autoimmune disease caused by the interaction of genetic and environmental factors. Among the environmental factors, infectious diseases and type of diet play the most important role.

Key role of PI3Kγ in monocyte chemotactic protein-1-mediated amplification of PDGF-induced aortic smooth muscle cell migration.

BACKGROUND AND PURPOSE: Vascular smooth muscle cell (SMC) migration within the arterial wall is a crucial event in atherogenesis and restenosis. Monocyte chemotactic protein-1/CC-chemokine receptor 2 (MCP-1/CCR2) signalling is involved in SMC migration processes but the molecular mechanisms have not been well characterized. We investigated the role of PI3Kγ in SMC migration induced by MCP-1. EXPERIMENTAL APPROACHES: A pharmacological PI3Kγ inhibitor, adenovirus encoding inactive forms of PI3Kγ and genetic deletion of PI3Kγ were used to investigate PI3Kγ functions in the MCP-1 and platelet-derived growth factor (PDGF) signalling pathway and migration process in primary aortic SMC. KEY RESULTS: The γ isoform of PI3K was shown to be the major signalling molecule mediating PKB phosphorylation in MCP-1-stimulated SMC. Using a PI3Kγ inhibitor and an adenovirus encoding a dominant negative form of PI3Kγ, we demonstrated that PI3Kγ is essential for SMC migration triggered by MCP-1. PDGF receptor stimulation induced MCP-1 mRNA and protein accumulation in SMCs. Blockade of the MCP-1/CCR2 pathway or pharmacological inhibition of PI3Kγ reduced PDGF-stimulated aortic SMC migration by 50%. Thus PDGF promotes an autocrine loop involving MCP-1/CCR2 signalling which is required for PDGF-mediated SMC migration. Furthermore, SMCs isolated from PI3Kγ-deficient mice (PI3Kγ(-/-)), or mice expressing an inactive PI3Kγ (PI3Kγ(KD/KD)), migrated less than control cells in response to MCP-1 and PDGF. CONCLUSIONS AND IMPLICATIONS: PI3Kγ is essential for MCP-1-stimulated aortic SMC migration and amplifies cell migration induced by PDGF by an autocrine/paracrine loop involving MCP-1 secretion and CCR2 activation. PI3Kγ is a promising target for the treatment of aortic fibroproliferative pathologies.

[Risk factors of multiple sclerosis in Moscow population. I. Exogenous risk factors]. / Faktory riska razvitiia rasseiannogo skleroza v moskovskoi populiatsii. I. Ekzogennye faktory riska.

Descriptive epidemiologic investigations revealed the necessity of the exogenous influence for the development of multiple sclerosis (MS). By means of "case-control" method the relations of MS with exogenous factors were studied. On the first stage there were analysed questionnaire data on 250 "patient-control" pairs matched by age, sex, nationality and birth in Moscow or out of it. The questionnaire was elaborated on the basis of the epidemiologic one recommended for the epidemiologic studies in the countries of South-East Europe. Significant correlations were found between MS and exogenous factors, namely: "tonsillitis at the age under 15 years" and "predominance of meat in the diet at the age under 15 years". These associations were confirmed by the data of both stratificative, discriminative analysis and logic regression. More detailed questionnaire was used on the second stage in 110 "patient-control" pairs. The second study confirmed such associations and found the most significant connection between MS and both tonsillitis at the age of 7-15 years and consumption of smoked meat. The influence of both exogenous factors were probably conditioned by permanent antigenic stimulation of the immune system in predisposed individuals.