[Molecular mechanisms of neuroretinoprotection in primary open-angle glaucoma]. / Molekuliarnye mekhanizmy neiroretinoprotektsii pri pervichnoi otkrytougol'noi glaukome.

PURPOSE: To evaluate the effectiveness of neuroprotective therapy in patients with primary open-angle glaucoma based on specific biochemical markers of neurotrophy and neurodegeneration. MATERIAL AND METHODS: In the course of the study, lacrimal fluid (LF) of 23 patients (46 eyes) with stage I-II primary open angle glaucoma (POAG) aged 66.3±10.8 was examined. The control group consisted of healthy individuals (12 control LF samples). Local antihypertensive therapy was complimented with 10 intramuscular injections of retinalamin (GEROPHARM LLC, St. Petersburg) - a complex of peptides isolated from cattle retinas, administered 5 mg once a day. Enzyme immunoassay (ELISA) method was used to test LF for concentrations of brain-derived neurotrophic factor (BDNF) and neuron specific enolase (NSE) before and after the treatment. RESULTS: In healthy subjects, the content of BDNF was 0.83±0.06 ng/mL, NSE - 0.51±0.06 ng/mL. In patients with POAG, the indices were higher: BDNF was 1.39±0.85 ng/mL (p>0.05), NSE - 4.31±2.02 ng/mL (p<0.05). The patients with stage II-III POAG had a significant increase of BDNF concentration (1.37±0.41 ng/mL and 1.52±0.40 ng/mL respectively in stages II and III) indicating compensatory capabilities at these stages of the disease. The NSE marker was also high in these stages (4.16±2.44 ng/mL and 5.78±2.80 ng/mL, p<0.05), which indicates the degeneration of retinal ganglion cells. After Retinalamin® therapy, patients with stage II POAG had control group levels of marker proteins, while in stage III patients NSE content remained high. CONCLUSION: There is a compensatory increase of BDNF level and a pathological increase of NSE content in LF of POAG patients. The change in the content of neurotrophins in the LF was determined to depend on the stage of POAG. Thus, in stages II and III POAG there is a marked increase of NSE and a compensatory increase of BDNF. After the complex therapy including retinalamin in patients with stage II POAG, a decrease in initially high concentrations of BDNF and NSE in LF down to the control group values was noted. In stage III patients, signs of neurodegeneration persist in the form of high NSE values. Taking into account the positive dynamics of the neuronal marker content in LF in the complex therapy of POAG with Retinalamin®, timely neuroretinoprotection is recommended.

[The clinical laboratory criteria of infectious complications in primary patients with acute leucosis.]

The study was carried out with the purpose of investigating clinical laboratory features of immune reaction in primary patients with acute leucosis and their significance in development of infectious complications. The analysis was applied to indices of immunograms, main anti-inflammatory cytokines - IL-1ß, IL-6, IL-8 and FNOα, molecule of inter-cellular adhesion sICAM-1 and also expression of receptors to IgG (CD16, CD64) on cells of macrophage phagocyte component and intracellular content of myeloperoxidase. It is established that development of infectious complications is connected to imbalance of congenital immunity and is characterized by involvement into systemic inflammation anti-inflammatory cytokines FNOα, IL-6, molecule of inter-cellular adhesion sICAM-1 and reduced capacity of neutrophils to phagocytosis conditioned by insufficiency of membrane expression of receptors to IgG - CD16 combined with enzymatic insufficiency.

[Immunological aspects of chronic tonsillitis].

The objective of the present study was to identify clinical and laboratory criteria for the chronization of tonsillar pathology and propose methods for immunological rehabilitation of the patients based on the investigations into specific features of the immune response in the oropharyngeal region. A total of 371 patients presenting with chronic tonsillitis (CT) and 54 practically healthy subjects were available for observations. The study materials included saliva samples in which IF-α, IF-y, slgA, IgA, IgG, and IgE levels were measured along with extracellular peroxidase activity (immunoenzyme assay) and palatine tonsil biopsies where lymphocyte subpopulations were identified in the indirect immunofluorescence reaction as well as infection with Epstein-Barr virus, herpes simplex virus, and cytomegalovirus (by PCR). Acute tonsillitis was shown to be accompanied by the activation of antimicrobial local protective factors (interferons, peroxidase system, T- and B-lymphocytes, antibody production). CT in case of infection with Epstein-Barr virus was associated with the deficiency of antiviral and antibacterial protective factors in the oropharynx (interferons, NK-cells, peroxidase activity). The possibility of immune correction using interferons, interferonogens, and bacterial lysate-based preparations is substantiated. The complicated toxico-allergic forms of chronic tonsillitis are shown to develop from the combination of insufficiency of the protective factors (IgG) and the excessive content of IgE. Substitution therapy using antibodies (immunoglobulins for intravenous administration) is proposed as the method of choice for the management of chronic tonsillitis.

[Immunological aspects of inflammation of the upper respiratory tract].

The objective of the present study was to elucidate the immunoimmunological characteristics of mucosal membranes of the upper respiratory tract. Specific adaptive mechanisms of local immunity in the mucosal membranes of the upper respiratory tract were shown to depend on both localization and severity of the pathological processes. This finding can be used as a basis for the choice of the strategy of immunomodulating therapy for the patients with chronic inflammation of mucosal membranes and the improvement of the modes of its application for the treatment of acute inflammation.

[Immunopathogenesis of chronic inflammatory diseases of the pharynx].

The objective of the present study was to develop indications for immunological rehabilitation of the patients presenting with chronic laryngitis. Immunogenetic characteristics (including both local and systemic immunity) were elucidated in 54 practically healthy subjects and 110 patients with catarrhal, hyperplastic, and atrophic forms of chronic laryngitis. PCR-diagnostics was performed for the presence of herpes-viruses in conjunction with bacteriological studies. It was shown that the efficacy of the effector protective factors of the immune system (including its phagocytic and T-cell components) was insufficient to suppress the persistent Epstein-Barr virus infection combined with staphylococcal and streptococcal infections. The protection of laryngeal mucosa depended on the involvement of proinflammatory antibodies (IgE and IgG) in the inflammatory process and the severity of defects in the elimination mechanisms (affecting the phagocytic component and secretory antibodies). The compromised protective function created conditions for the long-term persistence of pathogens.

[Peculiarities of immunotherapy of inflammation of the upper respiratory tract: the results of 30-year investigations].

The results of 30 year investigations conducted at the Department of Otorhinolaryngology, Bashkir State Medical University, provide new knowledge about immunopathogenesis of acute and chronic inflammatory processes of the upper respiratory tract and oral cavity (rhinitis, sinusitis, tonsillitis, pharyngitis, laryngitis). Moreover, they create a basis for the development of new purpose-oriented methods of immunocorrection taking into consideration the severity and duration of the inflammatory process.

[The role of interleukin 1-beta in pathogenesis and treatment of recurrent suppurative rhinosinusitis].

The objective of the present work was to study specific immunogenetic characteristics of 1-beta interleukin (IL 1-beta) production and estimate the possibility of using recombinant IL 1-beta for the treatment of recurrent suppurative rhinosinusitis. It was shown that the low production of IL 1-beta attributable to the combination of genotypes +3953>T *C/*C and -511C>T *C/*TAND *t/*t is associated with a relapse of suppurative rhinosinusitis. The patients presenting with this disorder are in need of dispensary examination and repeated administration of recombinant IL 1 beta (betaleukin) during the period of exacerbation of suppurative rhinosinusitis.

[The application of immunoglobulins for intravenous administration for the combined treatment of paratonsillar abscesses].

The objective of the present study was to evaluate the possibility of using immunoglobilins for intravenous administration (IVIG) to treat the patients presenting with paratonsillar abscesses (PTA). The comparative assessment of the clinical and immunological status of 77 patients with PTA depending on the type of therapy (traditional or combined with the use of IVIG) and the occurrence of tonsillitis in the medical history (the newly diagnosed disease, frequent tonsillitis, relapses of PTA). The level s of immunoglobulins (sIgA, IgA, IgG and its subclasses, IgM, and IgE) in mixed saliva samples were determined by the immunoenzyme assay and the albumin level by the bromcresol method with the counting of relative secretion coefficients (RSC). Palatine tonsil (PT) biopsies were used to determine the absolute content of lymphocytes (Lf) that were classified into differentiation clusters (CD3, CD4, CD8, CD16, CD25, CD71, CD95, HLA-DR). The patients presenting with paratonsillar abscesses were characterized by impaired immune responsiveness of palatine tonsils manifest as reduced production of IgG (at the expense of IgG2). This reduction was especially pronounced in the cases with the burdened medical history (recurring tonsillitis and relapses of PTA). In such patients, traditional therapy resulted in suppression of the cellular component of immunity and IgG production. The treatment with IVIG increased the production of IgG antibodies in the patients with newly diagnosed tonsillitis; moreover it stimulates production of IgG and activated the T-cell component. At the same time, the administration of IVIG reduced the duration of hospital stay from 9.29±0.31 to 7.06±25 days and the number of PTA relapses. It is concluded that the low IgG content in the saliva may be an indication for tonsillectomy.

[The function of palatine tonsils in pathological changes of oral mucosa and the possibilities of immunorehabilitation].

The objective of the present study was to estimate the possibility of using imudon for the treatment of chronic generalized periodontitis (CGP) in the patients presenting with various forms of chronic tonsillitis (CT) based on the results of the study of local immunity of the oropharynx. A total of 92 patients with CGP were divided into 3 groups as follows: those without pathology of palatine tonsils (PT) (group 1), cases with compensated chronic tonsillitis (group 2), and patients with periodontitis and concomitant decompensated form of CT (paratonsilitis). The results of assessment of local immunity (from the analysis of immunocytograms of the PT surface and periodontal pockets along with the data on the immunoglobulin content in mixed saliva samples and blood plasma) give evidence of the specific features of local immune responsiveness depending on the state of palatine tonsils. The changes of local immunity characteristics after the treatment suggest the efficacy of the traditional treatment of chronic generalized periodontitis in the absence of NT pathology and the necessity of its supplementation with imudon herapy in the patients with CGP and compensated form of CT.

[Immune reactions of palatine tonsils in the patients with chronic tonsillitis and the possibilities for their immunological rehabilitation with the use of imudon].

The objective of the present study was to develop a rationale for the application of imudon (a bacterial lysate preparation)in the treatment of the patients presenting with chronic tonsillitis based on the elucidation of characteristics of local immunity in the oropharynx (determined from the results of cytograms, immunoenzyme assays for the quantitation of IgG, sIgA, IgA, and IgM antibodies, and calculation of the relative secretion coefficients). A total of 74 patients with chronic tonsillar pathology (24 children and 50 adults) were available for the observation along with 42 subjects having no tonsillar pathology with concomitant chronic bacterial rhinosinusitis. The control group was constituted by 25 practically healthy subjects. It was shown that the local application of imudon in the patients with the preserved function of palatine tonsils (in the absence of symptoms of chronic inflammation) produces the adequate response of the humoral and cellular immunity systems. In the patients with the simple form of chronic tonsillitis imudon therapy ensured statistically significant activation of congenital immunity including the phagocyte function and a tendency toward normalization of antibody formation. It is concluded that alteration of the function of palatine tonsils in the patients presenting with the toxico-allergic form (ТАФ-2) of chronic tonsillitis implies the necessity of surgical treatment (tonsillectomy).

[The characteristics of iron metabolism under iron-deficiency anemia and chronic disorders anemia].

The study investigated the issues of iron metabolism under iron-deficiency anemia and chronic disorders anemia and dependencies of production of IL-1? and sICAM-1 immunoinflammatory markers from degree of severity and duration of anemia. The study data indicates that under iron-deficiency anemia lactoferrin and sICAM-1 are the negative regulators of hemopoiesis. The inhibition of transferrin expression by the proinflammatory cytokines is one of the causes of inefficient hemopoiesis under chronic disorders anemia.

[Intraocular infection with herpesviruses and antiviral immunity in patients with age-related macular degeneration].

Polymerase chain reaction revealed Herpesviridae (Herpes simplex, Cytomegalovirus) in the lens substance in 46 patients operated on for age-related cataract. Thirty-two patients of them had age-related macular degeneration. Herpes simplex was found in 6 (18.8%) of the patients with age-related macular degeneration. At the same time there were signs of lacrimal fluid antiviral immunity imbalance with decreased IFN-gamma and TNF-alpha and increased IFN-alpha. The authors consider it advisable to perform antivirus treatment in patients with the above abnormality, preventing the active forms of herpetic infection.

[Cytokines production by immune system cells in patients with various forms of chronic rhinosinusitis]. / Prokuktsiia tsitokinov kletkami immunoi sistemy u bol'nykh s razlichnymi formami khronicheskogo rinosinusita.

Production of cytokines IL-1 beta, IL-8, TNF-alpha, IFN-alpha and IFN-gamma by blood cells and their level in paranasal sinus lavage fluid (LF) were studied in seventy two patients with chronic rhinosinusitis. It was found that in various forms of rhinosinusitis the production of proinflammatory cytokines is characterized by common features: IL-1 beta:IL-8:TNF-alpha averages 1:6.5:0.47. While in polypous rhinosinusitis synthesis of IFN-gamma was reduced. LF cytokine profile depends on the form of chronic rhinosinusitis. The polypous form, pyoinflammation, pyopolypous form are characterized by low concentration of TNF-alpha, lack of IL-1 beta, low production of IL-1 beta and interferons alpha and gamma, respectively.

[Immunological status and its changes in children during surgery on anterior eye segment]. / Immunologicheskii status i ego izmeneniia u detei pri provedenii operatsii na perednem otrezke glaznogo iabloka.

Nonspecific and specific immunity values were studied in 70 children before and in various periods after 74 operations on the anterior segment of the eyeball. In children with persistent autosensitization to ocular tissue autoantigens (alpha-crystalline and S-antigen) postoperative uveitis presented as an immunocomplex disease with signs of exhaustion of the functional potential of the phagocytosis and complement systems. In children without autosensitization uveitis was associated with immunity activation. Phagocytosis system and cooperation of lymphocyte subpopulations, including normal killers (CD16+), play an important role in prevention of sensitization to ocular tissue autoantigens. Therefore, complex immunological examinations of children before surgery and regular check-ups after it will help differentiate immunodeficiency from compensatory immunosuppression preventing autoimmune disease, which is important in prescription of immunostimulating therapy.

Some Parameters of Immune Status in Children before and after Cataract Extraction with Intraocular Lens Implantation.

An immunological study was performed in 71 children aged 6-15 years old. Twenty seven of these 71 patients have undergone surgery for congenital cataract, 23 - for traumatic cataract aspiration-irrigation with a posterior chamber intraocular lens implantation and 21 - for secondary intraocular lens implantation. The number of peripheral blood active T lymphocytes, CD4(+), CD8(+), HLA DR(+) lymphocytes and antibody response to lens (alpha-crystalline) and retina (S-antigen) proteins were determined. Tissue specific antibodies were revealed in cases of both increased and decreased T-cellular immunity parameters. Sensibilization to S-antigen at the background of HLA DR(+) lymphocytes increase and a decrease in other parameters of immunity that may be regarded as the autoimmune status was the most unfavorable prognostic sign. In these cases even after atraumatic surgery the risk of postoperative inflammation was rather high with development of chronicity.

[Immunologic correctors in combined treatment of paratonsillitis]. / Immunokorrektory v kompleksnom lechenii paratonzillita.

As shown by immunological examination of 47 healthy subjects living in polluted territories and 120 patients with paratonsillitis (PT), PT arises in T-cell and humoral immunodeficiency of the palatine tonsils. Conventional treatment fails to eliminate initial immunodeficiency, contributes to development of chronic inflammation and complications. Adjuvant treatment with local polyvalent pyobacteriophage and parenteral placental albumin improves local and systemic immunity, promotes a favourable outcome of acute inflammation in the tonsils.