THE STATE OF PROOXIDANT-ANTIOXIDANT BALANCE IN PROSTATE GLAND OF RATS WITH CRYOTRAUMA AND ITS CORRECTION WITH DRUGS OF NATURAL ORIGIN.

The article deals with evaluation of the prooxidant-antioxidant balance in the prostate gland of rats with prostate cryotrauma caused with the help of Wartner® on the basis of biochemical studies results. The restored glutathione, lipid hydroperoxides, diene conjugates, TBA products were investigated in the prostate homogenate, together with the state of sperm according to the following characteristics: quantity, pathological forms, motility and time of its preservation. Correction was performed using the following drugs: Chondroitin sulfate, Tribestan, Chondroitin sulfate in combination with Tribestan, Prostoplant forte and Bioglobin-U. The obtained results showed that the prostate cryotrauma in rats caused by Wartner® was characterized by intensification of lipid peroxidation processes and reduced antioxidant protection, which negatively affected the sperm. All the studied drugs had a normalizing effect on the processes of liperoxidation and the state of sperm. However, the most pronounced positive effect was obtained when using Chondroitin sulfate during prostate cryotrauma in rats.

Plasmonic silvered nanostructures on macroporous silicon decorated with graphene oxide for SERS-spectroscopy.

A method for fabricating surface-enhanced Raman scattering (SERS)-active substrates by immersion deposition of silver on a macroporous silicon (macro-PS) template with pore diameters and depth ranging from 500-1000 nm is developed. The procedure for the formation of nanostructured silver films in the layers of macro-PS was optimized. Silver particles of dimensions in the nano- and submicron-scale were formed on the external surface of the macro-PS immersed in the water-ethanol solution of AgNO3, while the inner pore walls were covered by smaller, 10-30 nm diameter, silver nanoparticles. Upon introducing the hydrofluoric acid to the reaction mixture, the size of nanoparticles grown on the pore walls increased up to 100-150 nm. Such nanostructures were found to yield SERS-signal intensities from CuTMpyP4 analyte molecules of the same order to those obtained from silvered mesoporous silicon reported previously. The tested storage stability for the silvered macro-PS-based samples reached up to 8 months. However, degradation of the SERS intensity under illumination by the laser beam during spectral measurements was observed. To improve the stability of the SERS-signal a hybrid structure involving graphene oxide deposited on the top of analyte molecules adsorbed on the Ag/macro-PS was formed. A systematic observation of the time evolution of the characteristic peak at 1365 cm-1 showed that the addition of the oxidized graphene layer over the analyte results in ∼2 times slower decay of the Raman intensity, indicating that the graphene coating can be used to enhance the stability of the SERS-signal from the CuTMpyP4 molecules.

[Methodological aspects of interpretation of thyroid-stimulating hormone reference intervals in the Northwest region megapolis hospital.]

The prevalence of subclinical hypothyroidism (SH) is large and according to various studies is from 3 to 21%. In the Russian Federation to date, there are no major epidemiological studies assessing the functional state of the thyroid gland. It seems relevant to study the TSH level in patients who turned to the clinical units of a large hospital in the North-West region to determine the prevalence of thyroid dysfunction in patients of different sex and age. 5,303 patients were examined, who applied to the I.P. Pavlov SPbSMU clinics for 2017. In all patients the level of TSH and free T4 was determined. SH was considered to increase the level of TSH more than 4.0 mIU/l at a normal level of free T4. Patients were divided into groups by age and TSH level in accordance with existing recommendations. Among the examined patients were 29.26% of men and 70.73% of women. The mean age was 55.08 ± 17.07 years. The TSH level had an abnormal distribution and averaged 2.77 mIU/l (TSH median 1.73 mIU/l). In women the level of TSH was significantly higher in all studied groups of patients (p = 0.0001). Among women, significant differences in the level of TSH between the elderly and young patients (p = 0.015) were found. The incidence of SH in the total group of patients was 10.1%. In the men surveyed, the incidence of SH was 7.3%, and in the female group - 11.3%. In the elderly patients, the incidence of subclinical hypothyroidism in women was 2 times higher than that of men. In most cases (77.4%) in patients with SH, the TSH level was in the range of 4.0-6.9 mIU / L. The clinical significance of minimal thyroid insufficiency requires further study.

NbN superconducting nanonetwork fabricated using porous silicon templates and high-resolution electron beam lithography.

Superconducting NbN nanonetworks with a very small number of interconnected nanowires, with diameter of the order of 4 nm, are fabricated combining a bottom-up (use of porous silicon nanotemplates) with a top-down technique (high-resolution electron beam lithography). The method is easy to control and allows the fabrication of devices, on a robust support, with electrical properties close to a one-dimensional superconductor that can be used fruitfully for novel applications.

[Analysis of prophylactic and therapeutic effect of probiotic preparations from position of new scientific technologies].

In this review new scientific technologies (genomics, proteomics, metabolomics, transcrip- tomics) were used to evaluate the prophylactic and therapeutic action of probiotics, which are a major component ofthe normal human microflora (microbiota). Modern terms, definitions, classification of probiotic preparations are provided in the paper, the list of the probiotics registered in the Russian Federation is also submitted. The review analyzes the majority of mechanisms of probiotics action on a human body. The problem of safe application of probiotics is considered along with the detailed characteristic of the most effective production probiotic strains. New scientific technology to assess the effects of probiotic bacteria on the various functions of the macroorganism are also examined. In the review the special attention is paid to discussion of effectiveness of the probiotics impact in chronic infectious and metabolic disease processes (atherosclerosis, lipid distress syndrome, type 2 diabetes, obesity, etc.), which are the most active during dysbacteriosis and the destruction of normal microflora. From data of this article clearly that new scientific technologies will allow us to establish the functions of proteins that regulate metabolic and signaling pathways and affect the expression of genes required for the adaptation of probiotic strains in contact with the human body. In this review it is shown that the successful solution of this problem is closely connected with application of new scientific technologies for studying the composition and functions of the human microbiota, methods of active influence on her, and also with development of more sophisticated and effective probiotic preparations.

[Commensal microflora and endogenous inductors of pathophysiological reactions of innate immunity].

This paper content analytical review of literature on commensal microflora and endogenous inductors of pathophysiological reactions of innate immunity. The important role of participation in the homeostasis of the intestinal microflora, the repair of tissue damage, maintaining the innate immune system in a state of physiological tone by interacting with receptors pattern recognition receptors. Effects of the interaction of components commensal flora and innate immune receptors play an important role in physiological processes of microorganism in maintaining the balance of the synthesis of pro-inflammatory and anti-inflammatory cytokines and antimicrobial substances.

[ENTEROTOXIGENICITY OF STAPHYLOCOCCUS AUREUS STRAINS, ISOLATED FROM BREAST MILK OF WOMEN, FEEDING CHILDREN WITH INFECTIOUS PATHOLOGY].

AIM: Determination of enterotoxigenicity and ability to synthesize TSST-1 in S. aureus strains, isolated from breast milk of women, feeding children with infectious pathology. MATERIALS AND METHODS: 35 S. aureus strains, isolated from breast milk of women feeding children with varying infectious pathology in hospitals and as outpatients were studied for the presence of staphylococci enterotoxins (SE) of types A and B and toxic shock syndrome toxin (TSST-1). Determination of SEA, SEB and TSST-1 was carried out by enzyme immunoassay. RESULTS: Toxins were detected in 94.2% of S. aureus strains. SEB was synthesized by 86.7%, SEA--34.3%, TSST-1--42.8% of S. aureus strains. Toxins were detected with equal frequencies in healthy women and women with inflammatory diseases of breasts. Differences in frequency of colonization of intestines of children receiving breast milk, infected with toxigenic and non-toxigenic staphylococci strains was not detected. CONCLUSION: A high frequency of occurrence of enterotoxins and TSST-1 in S. aureus, isolated from breast milk of the mother during infectious pathology in the child was discovered. Enterotoxigenic strains can be detected in breast milk in healthy women. Study of the role of breast milk, infected with S. aureus, producing SEA, SEB And TSST-1 in development of child pathology is necessary.

Superconducting nanowire quantum interference device based on Nb ultrathin films deposited on self-assembled porous Si templates.

Magnetoresistance oscillations were observed on networks of superconducting ultrathin Nb nanowires presenting evidence of either thermal or quantum activated phase slips. The magnetic transport data, discussed in the framework of different scenarios, reveal that the system behaves coherently in the temperature range where the contribution of the fluctuations is important.

[Bacterial lipopolsaccharides in pathogenesis of gynecological diseases and obstetric complications].

Analysis of literature data and author studies on the role of lipopolysaccharides (endotoxin) of Gram negative bacteria in women genital tract pathology and obstetric complications is presented. The role of endogenous infection associated with altered microecology of intestinal tract and vaginal biotopes of women in the development of endotoxinemia is discussed. The participation of endotoxin in embryo resorption, delay of intrauterine development and antenatal death of fetus, premature birth, pre-eclampsia, placental dysfunction is examined. The level of endotoxinema and pro-inflammatory cytokines is a marker of chronic endogenous infectious-inflammatory disease of various parts of genital tract with damage of a network of female reproduction system organs.

[Intestinal microflora, obesity and type 2 diabetes].

The review of data of the literature on a role of intestinal microflora, genetic features of a macroorganism, exogenic factors and character of a food is presented at obesity and a type 2 diabetes. Researches establish, that development in experimental animals of the induced obesity and the type 2 diabetes, depends on a diet and presence of intestinal microflora. The factors increasing permeability mucous intestines, promote a translocation of intestinal automicroflora and its toxins into macroorganism and a system blood-circulation. Long introduction LPS (endotoxin) of gram-negative bacteria to the special laboratory animals led to development of inflammatory reaction, adiposity and resistance to insulin. The specified phenomena did not develop at LPS introduction to the animals, who have lost receptor CD14 which is necessary for linkage and endotoxin action. Data about change of intestinal microflora and a role of immune infringements are discussed at obesity and the type 2 diabetes occurring into background of low-grade chronic inflammation and metabolic disorders.

[Ultrastructure of microbial biofilms during intercellular interactions of bacteria in communities].

Analysis of summarized data obtained by us on ultrastructure of microbial biofilms of opportunistic bacteria is presented. A complex ultrathin organization of lactobacilli, enterobacteria, staphylococci and enterococci biofilms discovered during electron microscopy is described. The presence of surface film and polysaccharide matrix that determine increased resistance of intrabiofilm bacteria against the effect of protective immune factors of the organism and etiotropic preparations is demonstrated in all the studied comminutes. A varied response of bacterial cells contained in the biofilm during antagonistic effect of symbiont probiotic bacteria was discovered.

[Frequency of occurrence of ivyC and pliC lysozyme inhibitors genes in clinical klebsiella strains].

AIM: Chromosomal ivyC and plasmid pliC lysozyme inhibitor genes frequency of occurrence detection in klebsiella strains of various origins. MATERIALS AND METHODS: 129 strains were studied including K. pneumoniae (n= 115) and K. oxytoca (n=14). Klebsiella strains were divided into 2 groups: group 1 - 62 strains (39 isolated in Kazan and 23 strains isolated from children with klebsiella infection in Moscow). Kazan strains were presented by isolates from young children receiving in-patient treatment regarding klebsiella (n=8), respiratory (n= 17), rotavirus (n=5) and purulent-inflammation infection ofnewborns (n=9). Group 2 (n=67) was composed of strains isolated from children that had received outpatient treatment regarding intestine dysbacteriosis in Kazan (n=37) and Moscow (n=30). ivyC and pliC gene detection was carried out by PCR (N.B. Perunova et al., 2012). RESULTS: Chromosomal ivyC gene determinants were isolated in 40.3% of cases (52 strains of 129), plasmid pliC gene - 6.9% (9 of 129). ivyC gene frequency of occurrence in klebsiella strains isolated from 39 ill children of Kazan was 46.6% of cases (18 of 39), in Moscow clinical strains - 95.5% (22 of 23) cases, wherein 6 strains had ivyC and pliC genes at the same time. Dysbiosis intestine strains had chromosomal ivyC gene at the frequency of 61.2% (41 of 67), 1 strain additionally had pliC gene. CONCLUSION: . The presence of ivyC and pliC lysozyme inhibitor genes in klebsiella clinical strains provides bacteria with selective advantages in various biotopes in the process of bacterial colonization of mucous membrane.

Energy metabolism disorders in rat salivary glands tissues in connection with chronic sodium nitrate intoxication.

The purpose of the research was the study of nitrite impact on energy metabolism in salivary gland tissues in connection with chronic nitrate intoxication. The study has been carried out on 100 Wistar rats, weighing 160-250 g, which were divided into following groups: the 1st group consisted of intact rodents (control); the 2nd group consisted of experimental rodents, where chronic nitrate intoxication has been reproduced during 14, 30, 60 and 90 days. Intoxication leads to hypoxia, which complications cause tissue hypoxia. Has been established that prolonged intake of nitrates in low doses leads to their accumulation in salivary glands tissues all these result in derangement of metabolism at the intermembrane cellular level. At the same time energy metabolism in salivary glands is inhibited, resulting in their dysfunction at the excretory and endocrine levels.

[Modifications of chemical composition of blood serum in chronic nitrate intoxication (experimental research)].

Nitrates (salts of nitric acid) are very common substances in nature and are present in almost all living organisms. Relevance of research about features of various pathological processes in chronic nitric intoxication significantly associated with the fact that the intake of nitro compounds has significantly increased in recent years, especially in rural areas where local water sources are used. Investigations were carried out on 20 white Wistar rats. Two series of the experiment ware held: Group I - intact animals (10 animals); Group II - animals after administration of sodium nitrate at a dose of 200 mg/kg in the form of an aqueous solution intragastrically for 60 days (10 animals). Chronic nitrate intoxication leads to a significant increase of the level of serum chondroitin rats with permanent indicators glycoproteins indicates that the products disorganization of proteoglycans from the bone to the blood serum. Increasing of overall level glycosaminoglycans and the third fraction (heparan sulfate), and reducing of the 2-nd fraction (chondroitin-4-sulfate) glycosaminoglycans in serum may be indicative of a chronic lesion of sodium nitrite intoxication general connective tissue (including bone tissues and liver parenchymal).

Effects during the cathode polarization of porous silicon.

The large inner surface of porous silicon (pSi) not only provides unique opportunities for introducing various foreign materials into the open pores, but is also responsible for a lot of processes during the pSi cathode polarization. PSi surface and contact effects are considered in the article. The space charge layer induced by both the surface states and the double electrical layer in the solution is shown to have a decisive influence on the electrical conductivity of the silicon skeleton in the pSi layer. Depending on the depletion degree of the pSi skeleton, the electrochemical deposition of metals is possible either on the entire pSi surface or pore filling from the bottom. The erbium hydroxide formation in the process of the cathode polarization of pSi in the solution of erbium salt is shown to have a chemical nature and is stimulated by the alkalization of the cathode space. The formation of erbium-containing deposits occurs by the following mechanism. First, hydrogen is electrochemically reduced at the cathode. This causes the ion imbalance and leads to the alkalinization in the space near the cathode. The alkaline medium creates conditions for the chemical process of the erbium hydroxide formation. Formed as a gel, erbium hydroxide is physically adsorbed on the cathode surface as a film. The components of the solution are necessarily included in the deposit composition. The accompanying oxidation and dehydrogenation effects during the cathode pSi polarization are considered. Moreover, during the pSi oxidation, the solid phase extends in the pore increases the steric factor, which is essential for the formation of internal oxygen bonds. These effects are characteristic features of any pSi cathode treatment. These formation rules are true for any lanthanide. The obtained results open wide prospects for practical application of Er-filled pSi as a promising material for practical biomedical application as prospective electrodes.

[Intestinal-brain axis. Neuronal and immune-inflammatory mechanisms of brain and intestine pathology].

Mutually directed connections between intestine and brain are implemented by endocrine, neural and immune systems and nonspecific natural immunity. Intestine micro flora as an active participant of intestine-brain axis not only influences intestine functions but also stimulates the development of CNS in perinatal period and interacts with higher nervous centers causing depression and cognitive disorders in pathology. A special role belongs to intestine microglia. Apart from mechanic (protective) and trophic functions for intestine neurons, glia implements neurotransmitter, immunologic, barrier and motoric functions in the intestine. An interconnection between intestine barrier function and hematoencephalic barrier regulation exists. Chronic endotoxinemia as a result of intestine barrier dysfunction forms sustained inflammation state in periventricular zone of the brain with consequent destabilization of hematoencephalic barriers and spread oF inflammation to other parts of the brain resulting in neurodegradation development.

[Application of multiplex PCR for analysis of polycomponent probiotic preparations].

AIM: Development of multiplex PCR for indication and differential analysis of CFU in a probiotic preparation containing 3 various species ofbifidobacteria (Bifidobacterium bifidum, B. longum, B. adolescentis) and 2 species of lactobacilli (Lactobacillus acidophilus, L. plantarum). MATERIALS AND METHODS; Multiplex PCR with primers to 16S RNA genes of 5 species of bacteria was applied. Samples of bacterial colonies were removed from solid nutrient medium and transferred into test-tube for multiplex PCR execution. Bacterial lysates were used as target-matrix for amplification and determination of presence of the required amplicons. RESULTS: Multiplex PCR for detection of CFU of each of the bifidobacteria and lactobacilli strains in samples of 5-component probiotic with accuracy up to species was developed. A reagent kit was fine-tuned and high reproducibility and specificity of the multiplex PCR method with the accuracy of 90 - 95% of cases was shown. CONCLUSION: The multiplex PCR method developed is recommended to be applied for CFU control of each bacterial component in a complex probiotic preparation.

[Antimicrobial peptides of lactobacilli].

Data on antimicrobial peptides (AMP) of lactobacilli, mechanism of their damagin effect, chemical nature and genetic control are presented. Regardless of the source of isolation AMP of lactobacilli except reuterin are peptides with low molecular weight (4 - 6 kDa), differ from each other by chemical structure, sensitivity to temperature, effect of various enzymes, active at neutral or more frequently low pH. Especially important are mechanisms ensuring fine regulation of phenotypic expression of bacteriocin synthesis and formation of immunity against their effect. Activity and most importantly the level of their production depend on the conditions in which these bacteria are present and are controlled by a three-component regulation system. This system includes signal peptide (pheromone), sensory histidine kinase, regulator protein activating transcription. Resistance of the producer to the effect of its own bacteriocin is ensured by the so called immunity protein. AMP of lactobacilli are able to influence septoformation, peptidoglycan and protein synthesis, affect cytoplasmic membranes causing their destabilization. Stages of this damaging effect are described: interaction of effector peptides with the membrane of the sensitive cell, positioning of the peptide in the region of connection with protein receptor, submerging into the core of the spiral structure membranes with the formation of a pore and exhaustion of ATP pool leading to cell death. Protection from AMP is determined by specific proteins blocking pore formation in the membrane by direct binding of damaging molecules or their receptors. Perspectives of further studies of the role of antimicrobial peptides of lactobacilli are discussed.

[Recognition of commensal microflora by pattern recognition receptors in human physiology and pathology].

Contemporary data on the interaction of commensal microflora and Toll-like pattern recognition receptors are presented. These receptors recognize normal intestine microflora in physiological conditions, and this interaction is necessary for the maintenance of homeostasis and damage reparation of the intestine, for the induction of heat shock cytoprotective proteins. As a side effect in disruption of immunologic tolerance and misbalance of protective immunological mechanisms, multiorgan pathologic changes of organs and tissues may develop, including chronic inflammation processes of various localization.

[Presence of genes of genotoxin associated with pks pathogenicity island in Escherichia coli M-17 probiotic strain].

AIM: Study the presence of genetic determinants of pks pathogenicity island containing clb (colibactin) genes in bacteria of the E. coli M-17 production strain by using PCR. MATERIALS AND METHODS: E. coli M-17 cultures isolated from biopreparations bificol (Microgen) and colibacterin (Biomed) and control strain obtained from Tarasevich State Institute on Standardization and Control (Moscow) were studied. Detection of genetic markers of colibacterin was performed by using multiplex PCR with 4 pairs of primers amplifying the main clb genes: clbB, clbN, clbA and clbQ, generating 575, 711, 981 and 820 bp amplicons, respectively. RESULTS: In genome of all the studied E. coli M-17 strains clbB, clbN, clbA and clbQ genes associated with the formation of genotoxic colibacterin were detected. CONCLUSION: Genome of E. coli M-17 bacteria used for production of probiotic preparations colibacterin and bificol contains genetic determinants ofgenotoxin that require further studies in terms of evidence of harmlessness of production bacteria.