Biological Diversity and Remodeling of Cardiolipin in Oxidative Stress and Age-Related Pathologies.

Age-related dysfunctions are accompanied by impairments in the mitochondrial morphology, activity of signaling pathway, and protein interactions. Cardiolipin is one of the most important phospholipids that maintains the curvature of the cristae and facilitates assembly and interaction of complexes and supercomplexes of the mitochondrial respiratory chain. The fatty acid composition of cardiolipin influences the biophysical properties of the membrane and, therefore, is crucial for the mitochondrial bioenergetics. The presence of unsaturated fatty acids in cardiolipin is the reason of its susceptibility to oxidative damage. Damaged cardiolipin undergoes remodeling by phospholipases, acyltransferases, and transacylases, creating a highly specific fatty acyl profile for each tissue. In this review, we discuss the variability of cardiolipin fatty acid composition in various species and different tissues of the same species, both in the norm and at various pathologies (e.g., age-related diseases, oxidative and traumatic stresses, knockouts/knockdowns of enzymes of the cardiolipin synthesis pathway). Progressive pathologies, including age-related ones, are accompanied by cardiolipin depletion and decrease in the efficiency of its remodeling, as well as the activation of an alternative way of pathological remodeling, which causes replacement of cardiolipin fatty acids with polyunsaturated ones (e.g., arachidonic or docosahexaenoic acids). Drugs or special diet can contribute to the partial restoration of the cardiolipin acyl profile to the one rich in fatty acids characteristic of an intact organ or tissue, thereby correcting the consequences of pathological or insufficient cardiolipin remodeling. In this regard, an urgent task of biomedicine is to study the mechanism of action of mitochondria-targeted antioxidants effective in the treatment of age-related pathologies and capable of accumulating not only in vitro, but also in vivo in the cardiolipin-enriched membrane fragments.

[Polypous pansinusitis with the deformation of the external nose in a 8 year-old child presenting with the primary ciliary dyskinesia syndrome]. / Polipoznyi pansinusit s deformatsiei naruzhnogo nosa u rebenka 8 let s sindromom pervichnoi tsiliarnoi diskinezii.

This article reports a rare observation of the development of chronic polypous pansinusitis with deformation of the external nose in a 8 year-old child presenting with primary ciliary dyskinesia syndrome. The patient underwent multiple surgical interventions in the preceding period. The key argument in favour of the definitive diagnosis was the results of investigation of ciliated epithelium biopsy taken from the nasal cavity and bronchi in combination with the data obtained by diagnostic endoscopy of the nasal cavity and nasopharynx supplemented by computed tomography. The proposed treatment strategy including endoscopic endonasal pansinusotomy, antibacterial therapy taking into consideration the sensitivity of the seeded microorganism, and hormonal therapy proved optimal for the management of the given patient.

[EFFECTIVENESS OF APPLICATION OF COMBINED THERAPY OF EARLY ERYTHEMA STAGE OF LYME DISEASE TAKING INTO CONSIDERATION IMMUNOGENESIS FEATURES].

AIM: Study innate and adaptive immunity in patients with migrating erythema, clinical effectiveness ofcombined therapy using Immunovac vaccine and dynamics of immunologic parame- ters as a result of the therapy. MATERIALS AND METHODS: 37 adult patients with migrating erythema were examined. The patients were divided into 2 groups: 1st gr. (14 individuals) - Immunovac by intranasal-subcutaneous method against the background of basic therapy; 2nd gr. (23 individuals) - 200 mg/day doxycycline therapy for 21 days. Phagocytic activity of blood neutrophils; TLRs expression on mononuclear leukocytes of peripheral blood (PBML) and skin cells in foci by flow cytometry with mAT against TLR2, 3, 4, 5, 6, 7, 8, 9 using flow cytometer FC-500; subpopulation composition of peripheral blood lymphocytes; levels of pro-, anti-inflammation and regulatory cytokines in blood sera by EIA method; IgG, 1gM, IgA in blood sera were studied in patients before treatment and 1 month after therapy. RESULTS: A high level of TLR2, 4, 7, 8 on skin cells in foci, TLR2, 4 - on blood cells; low content of CD95+ and CD25+, high-level of serum IL-lb, IL-2 and IL-4, an increase of general IgE level was detected in patients'with migrating erythema. Immunovac facilitated an increase of CD95+ and CD25+, IFN-y synthesis, reduced the level of general IgE in a more pronounced way than basic therapy. CONCLUSION: Inclusion of Immunovac into therapy of patients With migrating erythema facilitates increase of clinical effectiveness and correlates with correction of immunologic disorders.

[COMPARATIVE ACTIVITY OF INFLUENZA VACCINES: EFFECT ON LYMPHO- CYTE SUBPOPULATION STRUCTURE].

AIM: Study subpopulation structure of lymphocytes in healthy individuals under the effect of various influenza vaccines in an in vitro system. MATERIALS AND METHODS: Evaluation of immune- phenotype features of PBMCs, activated in vitro by immune-adjuvanted and unadjuvanted vaccines against influenza in healthy individuals, was carried out by using flow cytometry method. RESULTS: Grippol plus vaccine caused a more pronounced stimulating effect compared with subunit and split-vaccines on NK-cells, cells with markers of early activation CD45/CD25, induced the quantity of natural regulatory cells (CD4/CD25/Foxp3), increase of the number of B-cells and reduced the amount of cell types with apoptosis marker CD45/CD95. CONCLUSION: Immune-adjuvanted vaccine Grippol plus induced formation of effectors of both innate and adaptive immunity and possessed the most powerful potential regarding activation of various types of immune-competent cells compared with unadjuvanted vaccines.

[Features of dynamics of sera cytokines in patients with erythema multiforme during immunotherapy].

AIM: Study the features of cytokine profile in patients with exudative erythema multiforme (EME) and dynamics of basal level of pro-inflammatory and anti-inflammatory cytokines during immunotherapy. MATERIALS AND METHODS: 39 adult patients with erythema multiforme were examined. The patients were split into groups based on therapy variant. One group (14 individuals) received Immunovac-VP-4 against the background of basic therapy; the other (12 individuals)--cagocel against the background of basic therapy; comparison group (13 individuals) received only basic therapy; 15 individuals composed a group of healthy individuals. All the patients had the level of pro-, anti-inflammatory and regulatory cytokines determined in blood sera by solid-phase EIA method by using Biosource (Austria) test-systems at the beginning of the study and after the therapy. RESULTS: In patients with exudative erythema multiforme Immunovac-VP-4 therapy facilitated a significant (p < 0.05) increase of serum IFN-gamma level, insignificant (p > 0.05) increase of IL-1beta and decrease of IL-17. Whereas cagocel lead to an increase of IL-4 (p > 0.05), IL-2, IFN-gamma (p < 0.05) and decrease of TGF-beta and IL-12 (p < 0.05). At the same time basic therapy facilitated a significant increase of IL-5 and decrease of IL-6, IL-12, IFN-gamma. CONCLUSION: Immunovac-VP-4 facilitates the increase of secretion of IFN-gamma, IL-1beta against the background of TGF-beta that facilitates normalization of cooperation of cells in immune response including against viral infections, and thereby influencing the trigger factor in EME patients.

[Influence of Staphylococcus vaccine on functional activity of antigen-presenting cells].

AIM: Study the influence of staphylococcus vaccine on functional activity of antigen-presenting cells. MATERIALS AND METHODS: Mice intraperitoneally received 500 µg of "Staphylovac" vaccine. Phagocytic activity of peritoneal macrophages against Staphylococcus aureus 1991 was determined in animals at various time intervals. Phagocytic index (PI) and phagocytic number (PN) in smears made at 30 and 60 minutes of incubation were calculated. Dendritic cells (DC) were obtained from bone marrow precursors during cultivation with 20 ng/ml GM-CSF and 20 ng/ml IL-4 (BioSource International Inc., Belgium). At day 6 of incubation staphylococcus vaccine (50 µg/ml) was added to immature cells for induction pf DC maturation. DC phenotype evaluation was carried out by flow cytometry using monoclonal antibodies against cell antigens (Beckman Culter, USA). RESULTS: PI at 30 and 60 minutes of incubation increased by 0.12 - 1.4 times and 1.11 - 1.52 times, respectively, compared with control. PN at 30 minutes of incubation of cells with microbial suspension increased from 8.6 to 11.4% against 5.9% in control, at 60 minutes of incubation--from 7.7 to 8.1% against 5.1% in control. In DC culture during their incubation with the vaccine, content of cells with expression of intercellular adhesion marker CD38, antigen presenting marker MHCII and DC terminal differentiation marker CD83 increased. Expression of CD34 and CD14 was also noted, that may give evidence on partial direction of cell differentiation to macrophages. CONCLUSION: "Staphylovac" vaccine during intraperitoneal administrationt to mice had activating influence on functional activity of antigen-presenting cells and peritoneal macrophages.

[Effect of proteflazid on TLRs expression by mononuclear leukocytes of peripheral blood and epithelial cells of mucous membranes and skin in patients with herpes-associated erythema multiforme and erythema annulare centrifugum].

The article reports survey data on 23 patients with erythemas, including 19 patients with herpes-associated erythema multiforme (HAEM) and 4 patients with Darier's erythema annulare centrifugum (DEAC). Patients in the initial state (baseline) and after two weeks of therapy with proteflazid were characterized by measuring the levels of Toll-like receptor (TLR) expression in peripheral blood mononuclear cells (PBMC) and in epithelial cells of the throat and the skin. The TLR expression in PBMC and skin was assessed by flow cytometry with monoclonal antibodies (ICA) (Caltag Laboratories, USA; Hycult Biotech, Netherlands) against relevant antigens. In addition, patients were also characterized by the content of subpopulations of lymphocytes expressing surface markers CD3, CD4, CD8, CD16, CD21, CD23, CD72, CD25, and HLA-DR in the peripheral blood, which was measured by flow cytometry. The therapy with proteflazid in patients with both HAEM and DEAC led to normalization of the level of both T-cell and B-cell immunity, which was manifested by an increase in the total number of lymphocytes, CD3+, CD4+, CD21+, and CD72+. Measurements of the dynamics of TLR expression in the course of immunotherapy showed an increase in the number of TLR 2, 3, 4, 7, 8, and 9 in PBMC (which was especially pronounced for TLR2) and in epithelium of the pharyngeal mucosa and skin (increased expression of TLR3, 7, and 9).

[Influence of immunovac-VP-4 therapy on innate immunity effectors in patients with darier erythema annulare centrifugum].

AIM: Detection of features of functioning ofinnate and adaptive immunity pathways in patients with Darier erythema annulare centrifugum (EAC). MATERIALS AND METHODS: 14 EAC patients aged 14 - 52 years were examined. The patients were ranked based on therapy variant. The first group consisted of 6 patients who had received Immunovac-VP-4 (Immunovac) against the background of basic therapy; the second group (4 patients) received cagocel against the background of basic therapy; the third group (4 patients) received only basic therapy; the group of healthy individuals consisted of 15 individuals. All the patients had the level ofcytokines in blood sera determined by solid-phase EIA by using Biosource (Austria) test-systems. Evaluation of TLR expression in peripheral blood mononuclear lymphocytes and keratinocytes was carried out by flow cytometry method by using monoclonal antibodies (Catlag Laboratories, USA) against the corresponding antigens; evaluation of content of lymphocyte subpopulations in blood was carried out by using monoclonal antibodies by flow cytometry method on FacsCalibur flow cytometer (Becton Dickinson, USA). RESULTS: Immunotherapy by Immunovac and cagocel facilitated the increase of CD3+, CD4+, CD8+. Immunovac facilitated a significant increase ofinitially low values ofCD25+, CD95+ and normalization of CD72+; normalization of IgM level. Immunovac increased the level of serum IL-2, induced the increase of IFN-gamma synthesis in contrast to cagocel and basic therapy, the administration of those caused its decrease. TGF-beta increased during the course of Immunovac immunotherapy and decreased during basic therapy. In the course of basic therapy a significant increase of initially high level ofcytokine IL-I beta was observed. CONCLUSION: Immunovac therapy resulted in correction of content of lymphocyte populations, sera cytokines, facilitating the normalization of immunocompetent cell proliferation processes, activation of NK-cells, macrophages and at the same time suppression of DTH reactions. Immunovac facilitated the enhancement ofTLR3, 9 expression in the skin that indicates the inclusion ofintracellular receptor mechanisms of innate immunity.

[Effect of Immunovac-VP-4 and Kagocel immunotherapy on cytokine levels in patients with erythema nodosum].

Fixed erythema--a kind of clinical and histopathologic reaction, fixed drug eruption. The purpose of the study--the study of characteristics of the cytokine profile in patients with erythema and the dynamics of the basal levels of proinflammatory and antiinflammatory cytokines during immunotherapy. All 41 patients with fixed erythema at baseline and after treatment was carried out determination of levels of pro-, anti-inflammatory and regulatory cytokines in the serum by ELISA using test systems "Biosource" (Austria). In patients with fixed erythema Immunovac treatment increased serum IFN-gamma (p < 0.05), IL-1beta (p > 0.05), IL-6. While Kagocel led to an increase in IFN-gamma (p < 0.05), IL-1beta, IL-6 and reduction of TGF-beta (p < 0.05). At the same time in patients with fixed erythema basic therapy contributed to the significant increase in TGF-â and decrease in IL-10. Immunovac-VP-4 had the highest activity for the induction of IFN-gamma. Inclusion in the range of therapeutic and prophylactic measures in patients with fixed erythema immunomodulators promotes activation links innate and adaptive immunity triggers mechanisms, thus increasing the antiviral response in patients with erythema.

[Therapeutic bacterial vaccine Immunovac in complex treatment of patients with chronic pyoderma].

AIM: Assessment of therapeutic effect and immunologic parameters during use of Immunovac vaccine for complex treatment of chronic forms of pyoderma. MATERIALS AND METHODS: Ninety-five patients with different clinical forms of chronic pyoderma (furunculosis, hydradenitis, chronic ulcerative and ulcerative-vegetans pyoderma, folliculitis, impetigo etc.) were studied. Fifty-nine patients received immunotherapy with Immunovac vaccine together with basic therapy and 36 patients comprised control group treated only with basic therapy. Studied immunologic parameters were as follows: assessment of functional activity of lymphocytes, determination of lymphocyte subpopulations by flow cytometry, total immunoglobulins classes A, G, M by radial immunoduffusion, affinity of antibodies by enzyme immunoassay, levels of IFNalpha and IFNgamma. RESULTS: Use of Immunovac vaccine in complex treatment of patients with chronic forms of pyoderma enhanced clinical effect of basic therapy, which expressed in decrease of severity and frequency of disease relapses irrespective to clinical form and severity of pyoderma. Therapeutic effect during use of Immunovac vaccine amounted 84.7%, whereas in control group it was 41.6% after 12 months of follow-up. Increase of functional activity of neutrophils, subpopulation of lymphocytes with markers CD4+, CD8+, CD72+, affinity of antibodies as well as induced production of IFNalpha and IFNgamma was revealed. Correction of immunologic parameters correlated with positive results of patients treatment. CONCLUSION: Inclusion of bacterial polycomponent vaccine Immunovac in complex treatment of patients with chronic pyoderma promotes enhancement of therapeutic effect of basic therapy and correction of immunologic parameters.

[Evaluation of clinical efficiency of viferon gel for the treatment of acute rhinopharyngitis].

Because numerous studies have demonstrated that the majority of acute inflammatory diseases of the upper respiratory tract are associated with viral infection, interferon-based medicines are being extensively developed for non-specific therapy and prevention of acute respiratory viral infections (ARVI). The objective of the present study was to evaluate the efficiency of local application of viferon gel for the treatment of acute rhinopharyngitis from the results of examination and treatment of a group of outpatients with this pathology (n = 90). Viferon gel was introduced into each half of the nose at a dose of 0.5 ml 4-5 times daily. It was shown that timely prescription of this preparation accelerates the achievement of positive results of AVRI therapy and thereby reduces duration of the disease and prevents the development of bacterial complications in the upper respiratory tract.

[Life quality as an additional criterion to evaluate efficacy of treating vibration disease patients].

Studies covered as an additional criterion to evaluate efficiency of treating vibration disease patients. Studies covered life quality in 40 males having vibration disease during the treatment course. Before the treatment, all the examinees demonstrated decrease in all life quality parameters especially of "role physical functioning" (16.89 points), general health (38.39 points), role emotional functioning (39.64 points). After the treatment most the parameters reliably improved, besides physical and social functioning. The authors recommend SF-36 life quality questionnaire to evaluate treatment efficiency for occupational diseases.

[Life quality of workers in machinery plants of Moscow region].

Questionnaires SF-36 and NJ-29 were used to examine 107 workers including 33 ones exposed to vibration, 27 ones - to various hazards mostly chemical, and 47 individuals without any exposure. Life quality corresponding to normal was pointed out by 80.4% of the examinees throughout the whole select, but the minimal one - by 75.8 % of the workers exposed to vibration. The latter group examinees had lower life quality in Pain scale (76 points), General Health scale (60.51), Vitality (63.3), Social functioning (72 points). In all the groups, psychic health was decreased, according to self-estimation of the examinees (69.01; 75.26; 71.92). The authors recommend inclusion of Questionnaire SF-36 into examination methods in periodic medical workups.

[Hemorheological activity of Gymnemy sylvestre extracts in streptozotocin-induced diabetes].

Extracts of Gymnemy sylvestre (GS) exhibit hemorheological activity. The most pronounced effect was observed for GL extract in 25 wt % concentration, which (i) induced a decrease in the viscosity of blood and washed erythrocyte suspensions in the entire range of shear rates by a factor of 1,3 (ii) reduced the degree of deformability of red blood cells, (iii) increased the degree of osmotic resistance of erythrocytes by 21.3%, (iv) increased the intensity of fluorescence of DSM+ probe in erythrocyte suspensions by a factor of 1.5, and (v) decreased the degree of anisotropy, thus generally improving the viscoelastic properties of the erythrocyte membrane and preventing the thrombocyte aggregation. In this respect, the GS extract activity exceeded that of Tanakan.

[Indications and contraindications to glomectomy in patients with bronchial asthma]. / Pokazaniia i protivopokazaniia k gloméktomii u bolnykh bronkhialnoi astmoi.

Thirty-year experience in surgical treatment of more than 3,000 patients with severe and moderately severe bronchial asthma showed that unilateral glomectomy produces a stable positive result in 69.5% of patients in follow-up repiods of two and more decades. Clinical recovery occurred in 23.2% of patients. Immunocorrection methods, such as hemosorption, plasmapheresis, plasmacytopheresis, xenosplenoperfusion, and the use of splenoperfusate raise the efficacy of the operation to 80-90%. The indications and contraindications for glomectomy in patients with bronchial asthma and methods for immunocorrection treatment of patients after glomectomy were developed.

[Experience with lamictal in the treatment of outpatients with resistant epilepsy]. / Opyt primeneniia lamiktala dlia lecheniia bol'nykh rezistentnoi épilepsiei v ambulatornykh usloviiakh.

The article summarizes the results of lamictal treatment in 93 patients with resistant epilepsy. Lamictal was used in a dose of 50-200 mg a day as an auxiliary drug in the treatment with other anticonvulsants. Its therapeutic efficacy was analyzed in relation to the form of epilepsy, the type of seizures, dosage of lamictal duration of therapy, and as patients' sex, age, and social activity. In the total group, 17.2% of the patients have remissions, in 48.4% the frequency of seizures frequency was reduced (> 50%) and 34.4% of the patients exhibited a less pronounced effect (< 50%). When combining lamictal and valproates, the best results were obtained in generalized seizures, especially in idiopathic generalized epilepsy, and in young and middle-age female patients with active social functioning.