[Comparative analysis of informative-diagnostic properties of mucosa immune-reactivity parameters].

AIM: Study the features of immune-reactivity expression in mucosa depending on their topicity and etiopathogenesis of the pathological process. MATERIALS AND METHODS: Data from 30 clinically healthy children and 77 children with acute and recurrent diseases of respiratory tract: 51--with acute and 15--with chronic bronchitis; as well as 132 women: 41--with active stage of acute urogenital chlamydia infection, 29--with recurrent chronic process, 30--with non-recurrent form and 32 clinically healthy women were analyzed. Saline and urogenital tract mucosa discharge was analyzed for IgG, sIgA and secretory component, IL-1beta, 4, 6, 8, 9, 10, 12, IFNgamma, TNFalpha and GM-CSF, TLR-2, TLR-3, TLR-4, TLR-8 gene expression levels as well as content of lysozyme, total protein and leucocytes. RESULTS: Solidity, universality and practically single-stage triggering of mucosa immune reaction mechanisms to intervention by foreign agents regardless of their localization was confirmed. A dependence of immune-reactivity expression on the form of pathologic process, its localization and qualitative and quantitative characteristics of the infectious agents was clearly seen. The highest level of clinical-laboratory and immunological parameters is inherent for patients with acute processes in urogenital tract (cervical canal and urethra), especially cause by mixed infections. CONCLUSION: Immune diagnostic parameters of mucosa among which TLR system is especially notable have high information properties allowing not only diagnostics of inflammatory process but also differentiating its form and character our course.

[Molecular-genetic and phylogenetic characteristic of Streptococcus pneumoniae strains isolated from patients with meningitis and carriers].

AIM: Analyze genetic and phylogenetic interrelations between S. pneumoniae strains isolated from meningitis patients and carriers. MATERIALS AND METHODS: 23 S. pneumoniae isolates (9 from bacterial meningitis patients, 9 from nasopharynx of bacterial carriers, 5 strains from museum collection of Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology) were studied. S. pneumoniae ATCC 49619, S. mitis ATCC 49456 served as control strains. S. pneumoniae serotype determination was carried out in latex-agglutination reaction and quelling reaction. Multiplex PCR according to WHO protocols was used for molecular-genetic study and pneumolysin (ply), autolysin (lytA), surface cellular adhesin A (psaA) and capsule polysaccharide (cpsA) gene determination. Multilocus sequence-typing was carried out according to WHO scheme for 7 "housekeeping" segments--aroE, gdh, gki, recP, spi, xpt and ddl. Computer programs from available internet resources were used for data processing and dendrogram building. RESULTS; The S. pneumoniae isolates analyzed were established to belong to 19 sequence types that may be combined into 4 subclusters. Results of molecular-genetic and serologic typing were completely comparable. CONCLUSION: Attribution of isolates from the same serotype and serogroup to different sequence-types gives evidence on the ongoing changes within serotype and as a result changes in allele profile of circulating S. pneumoniae isolates. Membership of isolates in separate subclusters gives evidence on close evolution relationship between isolates obtained from patients with bacterial meningitis and carriers. Certain isolates had not previously been registered in Russia and were probably imported from the territories of other countries.

[The phylogenetic position of Chlamydia strains isolated from monkeys and humans with Chlamydial pathology in the family Chiamydiaceae. Genotypic and phenotypic properties of this pathogen].

Based on the results of the comparative analysis concerning relatedness and evolutional difference of the 16S - 23S nucleotide sequences of the middle ribosomal cluster and 23S rRNA I domain, and based on identification of phylogenetic position for Chlamydophila pneumoniae and Chlamydia trichomatis strains released from monkeys, relatedness of the above stated isolates with similar strains released from humans and with strains having nucleotide sequences presented in the GenBank electronic database has been detected for the first time ever. Position of these isolates in the Chlamydiaceae family phylogenetic tree has been identified. The evolutional position of the investigated original Chlamydia and Chlamydophila strains close to analogous strains from the GenBank electronic database has been demonstrated. Differences in the 16S - 23S nucleotide sequence of the middle ribosomal cluster and 23S rRNA I domain of plasmid and non-plasmid Chlamydia trachomatis strains released from humans and monkeys relative to different genotype groups (group B- B, Ba, D, Da, E, L1, L2, L2a; intermediate group - F, G, Ga) have been revealed for the first time ever. Abnormality in incA chromosomal gene expression resulting in Chlamydia life and development cycle disorder and decrease of Chlamydia virulence can be related to probable changes in the nucleotide sequence of the gene under consideration.

[Molecular mechanisms of induction of innate immunity].

Cellular and molecular mechanisms of congenital immunity at different levels are discussed including single cell expression patterns and intracellular localization of individual TLR, the use of adapter molecules for generation of activation signals in response to microbial and non-microbial pathogens, soluble trap receptors, and intracellular negative regulators.

[Modern methods of laboratory diagnostics of Chlamydia infections].

Need for further improvement of methods for verification of etiological agent of urogenital and respiratory chlamydiosis on the basis of increased biotechnological requirements to antigens for serological reactions, primers for PCR assay (refinement of connection of primers with microorganism's zones of genome most significant for its life activity or formation of most diagnostically significant complexes of primers), and selection of cultivating conditions considering the predicted features of clinical strains of the agent was substantiated.

[The microflora of vaginal, gutter, and intestinal bioptats of women with a threat of early miscarriage].

A complex simultaneous assessment of the microbiota (the aerobic and anaerobic links as well as the parietal and lumen components) of the gutter, vagina, and intestines of women with a pathological pregnancy was performed. In 30% of women the study revealed system dysbiotic changes. Local immune reactivity was decreased, which may be considered a provoking factor. In conclusion, complex microbiological examination makes it possible to objectivize the picture of the pathological process and its outcome. A criterion for the administration of correcting measures is offered.

[The role and biological significance of toll-like receptors in the anti-infectious resistance of the organism].

Modem conceptions of the role of toll-like receptors (TLR) in the innante immunity mechanisms realization and data on the interaction between TLR and pattern-associated molecular proteins of microbial or endogenic origin are presented in the review.

[Microbiologicaland immunological criteria for estimation of ureaplasmosis treatment efficacy in women].

The role of surface and parietal vaginal microbiocenosis and immunoglobulins in development of infectious process, in prediction of resistance of causative microorganism to antibiotics and treatment efficacy was demonstrated on group of women with ureaplasmosis. Evaluation of anaerobic part of vaginal microbiota contemporary with its aerobic part reliably increased informative value of microbiological test in women with urogenital diseases. There are reasons to include interferon preparations into the complex therapy of ureaplasmosis.

[Monkeys as subjects for study of immunobiological preparations].

The parameters of colon microbiocenosis were evaluated in healthy animals belonging to 6 species of marmosets; its disorders typical of patients with different forms of acute intestinal infections were revealed. Bifidoflora of young monkeys was characterized. The study demonstrated multiple similarities of the microflora of monkeys and humans, including small children. A preclinical study of dry bifidin, a probiotic, revealed its advantages over the commercial bifidumbacterin. 90 monkeys were used for preclinical evaluation of complex immunoglobulin preparation (CIP) and a combination of CIP with interferon (kipferon in suppositories). The study demonstrated sanifying and microflora-normalizing effects, increase of anti-microbial antibodies and serum interferon after both parenteral and rectal administration. The protective activity of a new variant of the probiotic Acilact in exposure to ionizing radiation and anticancer chemotherapy under experimental conditions

[The microbiological and immunological characteristics of disbiotic disturbances of the biotopes of the mucose membranes of the respiratory and urogenital tracts].

The study consisted in comparison of the microecology and the parameters of the humoral immunity of the biotopes of the respiratory and urogenital tracts under normal conditions and in inflammatory processes caused by bacterial agents. The study revealed significant changes in the microbiocenosis of the respiratory and urogenital tracts, caused by decline of indigenous microflora and increase of the content of conditionally pathogenic microorganisms. These changes depended on the degree of the infectious process severity. Measurement of the humoral immunity parameters revealed a significant correlation between the content of conditionally pathogenic microorganisms and the levels of M and A immunoglobulins, as well as secretory IgA and free secretory component (sc) in the vaginal secretions of patients with non-specific inflammatory diseases of the genital tract, as well as G and A immunoglobulins, secretory IgA, and sc in the saliva of patients with chronic inflammatory diseases of the respiratory tract.

[Microecology and humoral immunity characteristics of the vagina in women with nonspecific inflammatory diseases of the genitals].

The complex cytological, microbiological and immunological examination of 90 female patients with nonspecific inflammatory diseases of the genital tracts and 30 clinically healthy women (the control group) was carried out. The examination revealed significant microbiocenosis changes in the lumen and the parietal area of the vagina, depending on the severity of the infectious process: a decrease in the level of lactobacilli, an increase in the content of opportunistic facultative anaerobic microorganism in the lumen and obligate anaerobic bacteria in the parietal area. Pronounced correlation between the content of opportunistic microorganisms and the levels of IgM and IgA, as well as secretory IgA and free secretory component in vaginal secretions in patients in patients with non-specific inflammatory diseases of the genital tracts has been revealed.

[Formation of probioticotherapy in Russia].

Probioticotherapy and probioticoprophylaxis have been applied widely in Russia and the world of late. The article presents the main medical, strain-related, and biotechnological stages of their development in this country, in comparison with the results of the world practice. The authors substantiate appropriateness of creation of probiotics and which would contain either only growth medium components, able to activate normoflora (to increase colonization ability and stimulate production of biologically active substances) upon entering the organism, or only probiotic strain components and/or biologically active substances produced by biologically active strains in mono- or associative cultivation, or combination of the listed components.

[Interferon therapy of infectious diseases: the state of the problem and prospects].

The data contained in literature and obtained in our own investigations, aimed at the evaluation of the significance of interferon preparations for the correction of immunological disturbances are presented. A special place is given to the role of mild medicinal forms of interferon, the necessity of their use is grounded and good prospects for their inclusion into the complex therapy of infectious diseases are shown.

[The viral and bacterial nature of dysplasia and of cervical carcinoma]. / Virusno-bakterial'naia priroda displazii i raka sheiki matki.

The role of the infection component in etiopathogenesis of dysphasia and cervical carcinoma as well as optimization of their diagnosis and treatment schemes are discussed in the paper. On the basis of published data and authors' independent examinations, a tense relationship between the presence of dysphasia and cervical carcinoma, on the one hand, and sexually-transmitted genital infection and/or bacterial vaginosis present in the medial history, on the other hand, was verified. An intensity of vagina-microflora dysbacteriosis in genital clamidiosis and in dysphasia of cervical carcinoma as observed in women as well as an evaluation of immunoglobulins' levels in vaginal secretions can be a prognosticating criteria for a conducted treatment. A high efficiency and feasibility were shown of adding the recombinant alpha2-interferon to the combined treatment of genital clamidiosis and to preventing it from being chronic as well as to correcting the dysplastic impairments an to preventing the malignant neoplasms in the neck of uterus.

[Diagnostic and prognostic significance of characteristics of serum interferon antiviral activity in chronic and acute diffuse liver diseases]. / Diagnosticheskaia i prognosticheskaia znachimost' pokazatelei protivovirusnoi aktivnosti syvorotochnogo interferona pri khronicheskikh i ostrykh diffuznykh zabolevaniiakh pecheni.

The interferon (IFN-alpha) level and its antiviral activity were investigated in 236 patients, suffered from the chronic diffuse liver disease (CDLD), including 121 patient with chronic hepatitis (CH), 115 patients with hepatocirrhosis (HC) and 26 patients with acute viral hepatitis (AVH). This permitted to elaborate the pathogenetic and prognostic value of these indices in CH, AVH and HC. The analysis of the variations of IFN-alpha antiviral activity in patients with CDLD in dependence on the etiology, activity of the pathologic process, CH stages by CHild-Pugh graduation, the presence of the portal hypertension and its complications was carried out for the first time. The antiviral activity in the patients suffered from HC with progression of the disease, aggravation of the portal hypertension, development of the decompensation along with persisted elevated IFN-alpha concentration decreased. The main mechanisms modulating IFN-alpha antiviral activity in peripheral blood of the patients suffered from CDLD have been determined. The use of the suggested indices in the combination with other methods of the examining significantly extends the possibilities of the diagnostics, permits to evaluate the reserve possibilities of the organism and to detect the strategy of the immunomodulating treatment. The determination of the IFN-alpha antiviral activity in serum in dynamics is recommended for the control of the therapy of the patients with CDLD and AVH.

[Vaginal microflora in girls of prepuberal age]. / Mikroflora vlagalishcha u devochek prepubertatnogo vosrasta.

The bacteriological study of vaginal microflora in 24 clinically healthy girls aged 7-8 years was carried out. Two criteria of normal vaginal biocenosis in girls of prepuberal age were proposed. The proportion of hemolytic bacteria in the vagina of a girl of prepuberal age could reach 100% of all microflora, provided the total bacterial count (TBC) exceed average values. A high proportion of hemolytic bacteria in the vaginal microflora of girls of prepuberal age in combination with a high level of TBC (even with TBC not exceeding the upper limit of its normal value) could probably by regarded as a border state. No fungi of the genus Candida should be isolated from vagina in girls of prepuberal age. Facultative anaerobic microflora was represented mainly by Staphylococcus epidermidis and S. saprophyticus. In 64.3 +/- 12.8% of cases bifidobacteria were detected in the girls vagina.

[Anti-Trichomonas activity of metronidazole in the presence of immunobiological preparations]. / Protivotrikhomonadnaia aktivnost' metronidazola v prisutstvii immunobiologicheskikh preparatov.

The minimal doses of metronidazole, capable of the irreversible immobilization of Trichomonas in the presence of one antiprotozoan preparation and after the addition of recombinant tumor necrosis factor (TNF), recombinant gamma-interferon and complex immunoglobulin preparation (CIP) into the culture medium, were determined on 4 T.vaginalis isolates, obtained on day 2 after the inoculation of material from the mucous membrane of the urogenital organs of patients (incubation at 37 degrees C). After 12-hour incubation of Trichomonas with immunobiological preparations their sensitivity to metronidazole increased 2-fold. After the simultaneous introduction of TNF, gamma-interferon and CIP into the culture medium, the sensitivity of Trichomonas to the action of metronidazole increased 5- to 7-fold. The introduction of an additional dose of TNF into the culture medium, but without CIP led to the preservation of the motility in a small number of these microorganisms. The use of human albumin instead of CIP at the same concentration (15 g/l) in the presence of TNF and gamma-interferon ensured the complete immobilization of Trichomonas in all isolates.

[A comparative study of the information value of the immunofluorescence and immunochromatographic identification of Chlamydia trachomatis antigens in smear material from the cervical canal and of the cytological picture of a vaginal discharge in pregnant women]. / Sravnitel'noe izuchenie informativnosti immunofliuorestsentnoi i immunokhromatograficheskoi identifikatsii antigenov Chlamydia trachomatis v soskobnom materiale iz tservikal'nogo kanala i tsitologicheskoi kartiny vaginal'nogo otdeliaemogo u beremennykh.

The cytological picture of the vaginal discharge and scrape material, obtained from 30 pregnant women of the control group (not infected with C.trachomatis) and 61 pregnant women with chlamydiosis; of these, in 42 women the comparative identification of chlamydiae by the methods of direct immunofluorescence and immunochromatography was carried out. Direct immunofluorescence was carried out with the use of a set of reagents "MicroTrak" (USA) and immunochromatographic identification was made with the use of a set of reagents "Clearview Chlamydia" (Britain). The comparison of the results of immunochromatography and direct immunofluorescence revealed that the sensitivity of the set "Clearview Chlamydia" was 100.0% in comparison with the data obtained in the examination of women with the use of the set "MicroTrak". The negative results coincided in 90.1% of cases. The common features of the cytological picture of vaginal samples taken from pregnant women were established. The optimum system of the examination of pregnant women suspected for chlamydiosis, as well as for the evaluation of the effectiveness of its treatment, was proposed.