[Factors of the hemostasis system as biomarkers of severe course of acute viral infections]. / Faktory sistemy gemostaza kak biomarkery tyazhelogo techeniya ostrykh virusnykh infektsii.

The authors give literature review of hemostasis and immune system factors intraction as main biomarkers of a severe cause of viral infectious diseases. Pro-inflamatory cytokines as the main markers of inflammation, can serve both as biomarkers of the clinical severity of the infectious process and reflect the state of the hemostatic and fibrinolytic systems, since components of these systems are present in various structures of the central nervous system and affect the development of neurons and synaptic plasticity. An inverse correlation has been proven between the concentration of D-dimer and the oxygenation index, and the development of DIC is not associated with the presence of respiratory failure in patients with influenza type A, while the ferritin concentration directly reflects the severity of the disease. One of the markers of endothelial damage may be soluble thrombomodulin, which, however, is rarely used in routine clinical practice. Cytoflavin is a highly effective pathogenetic drug that affects various parts of the hemostasis system, has anti-ischemic, antioxidant, antihypoxic, immunocorrective effect, which is indicated for any generalized infectious disease since its debut.

[Immunopatological and genetic aspects of pathogenesis of CNS lesions in VZV infection]. / Immunopatologicheskie i geneticheskie aspekty patogeneza porazhenii TsNS pri VZV-infektsii.

The review article provides information about the features of the Varicella-zoster virus (VZV), about the clinical manifestations of CNS damage in acute and chronic VZV infection in children and adults, about the mechanisms of interaction of the pathogen with the immune system during the development of the disease. The question of whether to consider neurological disorders in VZV infection as a complication or manifestation of the disease caused by a defective virus or the presence of subclinical immunodeficiency is discussed, which is confirmed by modern scientific studies. The critical mechanisms of immune defense against VZV, which are the main reason for the penetration of the virus into the CNS and the development of neurological disorders, as well as the relationship between VZV genotypes, the presence of mutations in the gE gene and the nature of the course, the identification of rare variants of the POLR3A, POLR3C, POLR3E and POLR3F genes associated with violation of IFNs induction, and the development of severe VZV infection, in which vasculopathy also occurs, which is the basis for the use of vascular drugs of complex action, such as Cytoflavin, the effectiveness of which has been proven by the authors. A special place is given to the analysis of intrathecal immunopathogenesis, which is likely to be associated with the presence and severity of neurological manifestations, their relapses. The issue of the causes of the development of a severe course of the disease in patients vaccinated against chickenpox, as well as the issue of resistance to specific antiviral drugs, probably associated with the presence of mutations responsible for the resistance of the virus to therapy, is discussed.

[Herpesviruses and biomarkers in disseminated encephalomyelitis and multiple sclerosis in children (part II)]. / Gerpesvirusy i biomarkery pri disseminirovannom entsefalomielite i rasseyannom skleroze u detei (chast' II).

Recently, the problem of demyelinating diseases in children is still very acute. This occurs, on the one hand, by high access and specificity of diagnostic methods and, on the other hand - by high morbidity of children different neuroinfectious diseases which can lead to demyelinating diseases. This literature review presents the currently available information on the autoantibodies and neurospecific protein role in the development of multiple sclerosis and acute disseminative encephalitis in children. The authors also describe their experience of complex etiopatogenic therapy and cytoflavin use that helps to reduce frequency and expression of demyelinating process and endothelium dysfunction in case of active herpesvirus infection.

[Herpesviruses and biomarkers in disseminated encephalomyelitis and multiple sclerosis in children]. / Gerpesvirusy i biomarkery pri disseminirovannom entsefalomielite i rasseyannom skleroze u detei.

The relevance of the study of demyelinating diseases is due to their increasing frequency in children, clarification of the role of infectious agents in their genesis, as well as the possibility of transformation of disseminated encephalomyelitis into multiple sclerosis. The literature review presents the currently available information on the causes of the development of demyelinating diseases, biomarkers of disseminated encephalomyelitis and multiple sclerosis, the causes of an unfavorable course and possible laboratory parameters indicating the transition from one disease to another, which can be used as prognostic factors. The authors also noted the experience of the authors on the importance of adequate etiopathogenetic therapy in changing the nature of the course of the disease, in particular, when confirming the relationship between the frequency of exacerbations of ADEM and MS with the activation of herpesvirus infections, courses of specific antiviral therapy are effective, as well as pathogenetic therapy aimed at correcting endothelial dysfunction using the drug cytoflavin.

[Gerpes viruses and multiple sclerosis]. / Gerpes-virusy i rasseiannyi skleroz.

AIM: To study the efficacy of L-lysine aescinat in the treatment of vascular and microvascular disorders in patients with cerebral venous dystonia. MATERIAL AND METHODS: Sixty-eight patients, 25 male and 43 female, aged from 25 to 56 years, with disturbances of venous cerebral blood circulation and venous outflow difficulties were examined. The examination included the assessment of cerebral hemodynamics using the algorithm of complex ultrasound examinations and functional status of the microcirculation by the laser Doppler flowmetry (LDF) at baseline and 10 days after treatment with L-lysine aescinat. RESULTS AND CONCLUSION: L-lysine aescinat improves intracranial venous outflow, significantly improves the functioning of microcirculation, while not affecting the normal type of microcirculation or changing it in the direction of improvement of hemodynamic parameters, has a modulating effect on the autonomic response, and can be recommended in the complex treatment of young and middle aged patients with disturbances of cerebral venous blood circulation with the predominance of vagotonia as well as hypersympathicotonia.

[The use of recombinant interleukin-2 in children with encephalitis].

OBJECTIVE: To study the efficacy of the domestic recombinant interleukin-2 (IL-2) in the complex treatment of encephalitis. MATERIAL AND METHODS: Forty patients, aged from 6 months to 17 years, were treated with the drug. A comparison group involved 35 patients who did not receive the drug. RESULTS: Recombinant IL-2 reduced (p<0.05) the aggravation of symptoms to 5.4±1.3 days, neurological deficit (1.6±0.2 EDSS scores at discharge from the hospital), frequency of exacerbations (from 22.9 to 5%) and frequency of cases with the development of multiple sclerosis during 3 years (from 17.1 to 2.5%). Parameters of the drug efficacy were correlated with positive changes in immunological parameters after 3-4 days of treatment. The study of multimodal evoked potentials demonstrated the positive effect of the drug on the central afferent conduction times. The follow-up MRI examination showed the decrease in the frequency of focal changes. CONCLUSION: Recombinant IL-2 is recommended for treatment of children with encephalitis.

[The immunologic factors in cerebrospinal liquor under bacterial, fungous or parasitic neuro-infections: a literature review].

The prognosis of course and outcome of inflectional inflammatory diseases of central nervous system, indicators of inflammatory reaction and immune response in cerebrospinal liquor in patients has been investigated.

[Enteropathogenic Yersinia and host cytokine system].

Data about interaction of virulence factors of Yersinia enterocolitica and Yersinia pseudotuberculosis with host immune system cells are presented in the review. Response of innate and adaptive immunity cytokine system in cultures in vitro and during experiment was characterized; scarce data on production of cytokines in patients with yersiniosis are presented.

[Human caliciviruses and an immune response].

The review deals with calicivirus infection that has long been known in animals, but also just recently disclosed in humans. Human caliciviruses induce outbreaks of acute gastroenteritis in all countries of the world, which makes this immunobiological research very actual. The history of this discovery, evolution of caliciviruses, the host resistance and immune response mechanisms are described in this review.

Clinical and immunological efficiency of anaferon (pediatric formulation) in calicivirus infection in children.

Therapy with anaferon (pediatric formulation) during the acute period of calicivirus infection shortened the duration of the main symptoms of the disease and period of virus release. Changes in the immunological status included increased production of IgA and IgM and activation of IFN-alpha synthesis.

[Salmonella enterica and cytokine system of the host].

Contemporary data on mechanisms of immune defense during salmonellosis as well as on ability of Salmonella to resist these mechanisms are presented in the review. Main emphasis is made on reaction of cytokine system of innate and adaptive immunity described in experimental and clinical studies.

[Effect of viruses on the host cytokine system].

The review considers recent data on the mechanism of action of viruses on the host cytokine system. The inhibitory and stimulant effects of viruses and their antigens on the production of cytokines, interferons in particular, are described. Examples of the behavior of specific viruses are given. Particular emphasis is laid on the viruses of the Herpesvididae family. The role of cytokine gene polymorphism in the pathogenesis is discussed.

[Resistance to a causative agent of infection and immune response].

An analytical literature review dealing with the problems of resistance to causative agents of infections. The review includes the data of experimental research, as well as the author's own immunological studies in children at the clinic of acute infections. Mechanisms of resistance at different phases of the infectious process, the multivalued role of Th1- and Th2-dependent responses in different infections, the role of vaccinal immunity in the resistance of children to the causative agents of vaccine-preventable infections (diphtheria and parotitis) are analyzed.

[Types of immune response in acute infectious diseases]. / Tipy immunnogo otveta pri ostrykh infektsionnykh zabolevaniiakh.

The author's concept on the system of self regulation of immune response is described. Four types of this response are proposed, which differ by total intensity of cytokine reaction, the development time as well as manifestation degree of non specific immunosuppression, and, most importantly, the profile of specific immune response to the antigens of the infective agent. These four types of immune response are closely linked with increased severity of clinical manifestations.

[Four levels (types) of immune reponse in children with viral parotitis infections]. / Chetyre urovnia (tipa) immunnogo otveta u detei, perenosiashchikh parotitno-virusnuiu infektsiiu.

Four levels (types) of immune response, differing by expression of cytokines (TNF-alpha, IL-1 beta, IL-4, and gamma-IFN) and immunoglobulins IgG2, IgG3, IgG4, and IgE) and by expression and time course of specific cell-mediated and humoral immune response, were detected in children with different clinical forms of mumps. Types 1 and 3 immune response are predominantly cell-mediated, while types 2 and 4 predominantly humoral during the acute phase of the disease. The cytokine and antigen-specific profiles of each type of immune response correlate with the severity of clinical course of mumps.

[The protective role of postvaccinal immunity in mumps in children]. / Protektivnaia rol' postvaktsinal'nogo immuniteta pri parotite u detei.

The immunological study of children with infectious parotitis (IP) without complications and with such complications as pancreatitis, meningitis or orchitis in the glandular form was carried out. In accordance with the previously proposed principle, 4 types of immune response (IR) were established on the basis of differences in initial resistance and the IR profile: cell-mediated immunity (types I and III) and humoral immunity (types II and IV). The patients included nonvaccinated children, as well as children vaccinated on epidemic indications, 3-6, 7-9, 10 and more years before infection. The comparative analysis of the number of IP cases with and without complications in the groups of children, divided according to their immunization history and the type of IR, revealed that postvaccinal immunity in children vaccinated on epidemic indications (less than a month ago) or 3-6 years before infection had protective potential, sufficient for the prevention of complicated forms of IP. Immunity obtained 7-9 years ago was effective for the protection from IP complications only in cell-mediated, but not humoral IR. Postvaccinal immunity obtained more than 10 years ago did not ensure the decrease in the occurrence of complicated forms of IP (in comparison with that in nonvaccinated patients) in children with any type of IR.

[Assessing the immune status in acute infections: a new methodological approach]. / Otsenka immunnogo statusa pri ostrykh infektsionnykh zabolevaniiakh: novyi metodologicheskii podkhod.

A pathogenetic approach to assessing the immune status of infectious patients is proposed. It consists in detection of the major variants of immune response in this or that infection by the characteristic time course of proliferative activity of phytohemagglutinin-stimulated T lymphocytes. Four similar types of immune response were distinguished in children with acute respiratory viral infection and oropharyngeal diphtheria by this method. These types differ by the intensity of antibody production, production of antigen-specific factors of immune defense (cytokines, immunoglobulins, and complement components), and the clinical symptoms. Antigen-specific profiles of each type of immune response in relation to the balance between two forms of defence, cell-mediated and humoral are described.

[Variants of immune response in children with acute respiratory viral infections]. / Varianty immunnogo otveta pri ostrykh respiratorno-virusnykh infektsiiakh u detei.

Four patterns of changes in the proliferative activity of T-lymphocytes in the lymphocyte blastogenesis test with phytohemagglutinin (PHA) are distinguished in children with acute respiratory viral infections (ARVI). The differences between these patterns are due to aggravated clinical severity of the infection process and enhancement of the cytokine reaction of macrophage monocytes. Comparison of immunological characteristics of response to ARVI in 4 groups of children showed that high reactivity of T-lymphocytes during the acute phase of disease (first and third variants) correlated with a relatively weak production of immunoglobulins and antiviral antibodies, while the suppression of T-lymphocyte response to PHA (second and fourth variants) is associated with expressed humoral profile of immune response by the level of immunoglobulin and antiviral antibody production. These data permit a hypothesis about the predominant generation of T x 1-like clones in children with the first and third variants of immune response and of T x 2-like clones in children with the second and fourth variants.