[Peculiarities of treatment with antidepressants in patients with schizoaffective disorder in the interictal period]. / Osobennosti terapii antidepressantami bol'nykh shizoaffektivnym rasstroistvom v mezhpristupnom periode.

OBJECTIVE: To investigate the effect of therapy with various classes of antidepressants on the quality of remission and adherence to therapy in patients with schizoaffective disorder (SAD) in remission. MATERIAL AND METHODS: We examined 87 outpatients, including 29 men (33.33%), 58 women (66.67%) diagnosed with SAD according to ICD-10 criteria (item F25), in whom 341 cases of remission were studied. The average age of the patients was 41.40±12.56 years. Cases of remission in patients receiving therapy with nonselective monoamine reuptake inhibitors (NSMRIs) were included in group 1 (n=228), cases of remission formed on therapy with selective neuronal reuptake inhibitors (SNRI) were included in group 2 (n=113). Clinical follow-up and statistical methods were used. RESULTS: In both groups, mood disorders in remission were represented by subdepression. Delusional disorders at the stage of remission were almost 7 times more common in group 1 (12.28%), compared with group 2 (1.77%). The duration of the interictal period in patients treated with NSMRIs was higher (504.0±60.67 days) compared with patients receiving SNRI (176.46±17.88 days). In group 2, residual affective-delusional symptoms in remission were significantly less common. Cases of refusal from therapy in group 2 were 12 times less frequent, which indicates a greater adherence to therapy in patients receiving SNRI. CONCLUSION: It is possible to recommend treatment with NSMRIs for patients with depressive affect in the structure of SAD to increase the duration of the interictal period. At the same time, for patients with SAD in the presence of delusional and affective-delusional symptoms, it is preferable to prescribe SNRI.

A Neurotoxic Insecticide Promotes Fungal Infection in Aedes aegypti Larvae by Altering the Bacterial Community.

Symbiotic bacteria have a significant impact on the formation of defensive mechanisms against fungal pathogens and insecticides. The microbiome of the mosquito Aedes aegypti has been well studied; however, there are no data on the influence of insecticides and pathogenic fungi on its structure. The fungus Metarhizium robertsii and a neurotoxic insecticide (avermectin complex) interact synergistically, and the colonization of larvae with hyphal bodies is observed after fungal and combined (conidia + avermectins) treatments. The changes in the bacterial communities (16S rRNA) of Ae. aegypti larvae under the influence of fungal infection, avermectin toxicosis, and their combination were studied. In addition, we studied the interactions between the fungus and the predominant cultivable bacteria in vitro and in vivo after the coinfection of the larvae. Avermectins increased the total bacterial load and diversity. The fungus decreased the diversity and insignificantly increased the bacterial load. Importantly, avermectins reduced the relative abundance of Microbacterium (Actinobacteria), which exhibited a strong antagonistic effect towards the fungus in in vitro and in vivo assays. The avermectin treatment led to an increased abundance of Chryseobacterium (Flavobacteria), which exerted a neutral effect on mycosis development. In addition, avermectin treatment led to an elevation of some subdominant bacteria (Pseudomonas) that interacted synergistically with the fungus. We suggest that avermectins change the bacterial community to favor the development of fungal infection.

[Genetic characterization of clinical Klebsiella isolates circulating in Novosibirsk]. / Генетическая Ñ Ð°Ñ€Ð°ÐºÑ‚ÐµÑ€Ð¸ÑÑ‚Ð¸ÐºÐ° ÐºÐ»Ð¸Ð½Ð¸Ñ‡ÐµÑÐºÐ¸Ñ Ð¸Ð·Ð¾Ð»ÑÑ‚Ð¾Ð² клебсиелл, Ñ†Ð¸Ñ€ÐºÑƒÐ»Ð¸Ñ€ÑƒÑŽÑ‰Ð¸Ñ Ð² Новосибирске.

72 clinical strains of Klebsiella spp. isolated from samples obtained from humans in Novosibirsk, Russia, were analyzed. Species identification of strains was performed using 16S rRNA and rpoB gene sequences. It was revealed that Klebsiella pneumoniae strains were dominant in the population (57 strains), while the remaining 15 strains were K. grimontii, K. aerogenes, K. oxytoca and K. quasipneumoniae. By molecular serotyping using the wzi gene sequence, K. pneumoniae strains were assigned to twenty-one K-serotypes with a high proportion of virulent K1- and K2-serotypes. It was found that K. pneumoniae strains isolated from the hospitalized patients had a higher resistance to antibiotics compared to the other Klebsiella species. Real-time PCR revealed that the population contained genes of the blaSHV, blaTEM, blaCTX families and the blaOXA-48 gene, which are the genetic determinants of beta-lactam resistance. It has been shown that the presence of the blaCTX sequence correlated with the production of extended-spectrum beta-lactamases, and phenotypic resistance to carbapenems is due to the presence of the blaOXA-48 gene. At the same time, the carbapenemase genes vim, ndm, kpc, imp were not detected. Among the aminoglycoside resistance genes studied, the aph(6)-Id and aadA genes were found, but their presence did not always coincide with phenotypic resistance. Resistance to fluoroquinolones in the vast majority of strains was accompanied by the presence of the aac(6')-IB-cr, oqxA, oqxB, qnrB, and qnrS genes in various combinations, while the presence of the oqxA and/or oqxB genes alone did not correlate with resistance to fluoroquinolones. Thus, the detection of blaCTX and blaOXA-48 can be used to quickly predict the production of extended-spectrum beta-lactamases and to determine the resistance of Klebsiella to carbapenems. The detection of the aac(6')-Ib-cr and/or qnrB/qnrS genes can be used to quickly determine resistance to fluoroquinolones.

Taxonomic composition and biodiversity of the gut microbiome from patients with irritable bowel syndrome, ulcerative colitis, and asthma.

To date, the association of an imbalance of the intestinal microbiota with various human diseases, including both diseases of the gastrointestinal tract and disorders of the immune system, has been shown. However, despite the huge amount of accumulated data, many key questions still remain unanswered. Given limited data on the composition of the gut microbiota in patients with ulcerative colitis (UC) and irritable bowel syndrome (IBS) from different parts of Siberia, as well as the lack of data on the gut microbiota of patients with bronchial asthma (BA), the aim of the study was to assess the biodiversity of the gut microbiota of patients with IBS, UC and BA in comparison with those of healthy volunteers (HV). In this study, a comparative assessment of the biodiversity and taxonomic structure of gut microbiome was conducted based on the sequencing of 16S rRNA genes obtained from fecal samples of patients with IBS, UC, BA and volunteers. Sequences of the Firmicutes and Bacteroidetes types dominated in all samples studied. The third most common in all samples were sequences of the Proteobacteria type, which contains pathogenic and opportunistic bacteria. Sequences of the Actinobacteria type were, on average, the fourth most common. The results showed the presence of dysbiosis in the samples from patients compared to the sample from HVs. The ratio of Firmicutes/Bacteroidetes was lower in the IBS and UC samples than in HV and higher the BA samples. In the samples from patients with intestinal diseases (IBS and UC), an increase in the proportion of sequences of the Bacteroidetes type and a decrease in the proportion of sequences of the Clostridia class, as well as the Ruminococcaceae, but not Erysipelotrichaceae family, were found. The IBS, UC, and BA samples had signif icantly more Proteobacteria sequences, including Methylobacterium, Sphingomonas, Parasutterella, Halomonas, Vibrio, as well as Escherichia spp. and Shigella spp. In the gut microbiota of adults with BA, a decrease in the proportion of Roseburia, Lachnospira, Veillonella sequences was detected, but the share of Faecalibacterium and Lactobacillus sequences was the same as in healthy individuals. A signif icant increase in the proportion of Halomonas and Vibrio sequences in the gut microbiota in patients with BA has been described for the f irst time.

Bacteriophages as Therapeutic Preparations: What Restricts Their Application in Medicine.

The increasing prevalence of bacterial pathogens with multiple antibiotic resistance requires development of new approaches to control infections. Phage therapy is one of the most promising approaches. In recent years, research organizations and a number of pharmaceutical companies have intensified investigations aimed at developing bacteriophage-based therapeutics. In the United States and European countries, special centers have been established that experimentally apply phage therapy to treat patients who do not respond to antibiotic therapy. This review describes the features of bacteriophages as therapeutic tools, critically discusses the results of clinical trials of bacteriophage preparations, and assesses the prospects for using phage therapy to treat certain types of infectious diseases.

A novel thermophilic Aeribacillus bacteriophage AP45 isolated from the Valley of Geysers, Kamchatka: genome analysis suggests the existence of a new genus within the Siphoviridae family.

A novel thermophilic bacteriophage AP45 and its host strain Aeribacillus sp. CEMTC656 were isolated from the Valley of Geysers, Kamchatka Peninsula, Russia. Bacteriophage AP45 was identified as a member of the Siphoviridae family by electron microscopy. It showed high thermostability and had a slow cycle of reproduction. The AP45 genome had 51,606 base pairs (bp) and contained 71 open reading frames (ORFs), 40 of them encoding proteins of predicted function. Genes encoding DNA and RNA polymerases were not identified, indicating that AP45 used host polymerases. Based on the ORF65 encoding putative endolysin, the recombinant protein rAP45Lys was developed and its peptidoglycan-hydrolyzing activity was demonstrated. The AP45 genome exhibited limited identity to other phage sequences; the highest identity, 36%, was with the genome of the thermophilic Geobacillus myovirus D6E. The majority of putative proteins encoded by the AP45 genome had higher similarity to proteins from bacteria belonging to the Bacillaceae family, than to bacteriophages. In addition, more than half of the putative ORFs in the AP45 genome were highly similar to prophage sequences of A. pallidus strain 8m3, which was isolated in north-east China. The AP45 phage and revealed prophages might be members of a new genus belonging to the Siphoviridae family.

Isolation and characterization of a group of new Proteus bacteriophages.

Four lytic Proteus bacteriophages, PM75, PM85, PM93, and PM116, which are active against multi-drug-resistant strains of P. mirabilis, were isolated from cattle and poultry samples. According to electron microscopy data, all of the investigated phages belonged to the family Podoviridae. They all demonstrated lytic activity against sensitive strains of P. mirabilis, and three of the phages, PM85, PM93, and PM116, are potential candidates for use in antibacterial treatment. The genomes and putative proteins of bacteriophages PM85, PM93, and PM116 were similar to those of Proteus phage vB_PmiP_Pm5460 [KP890822], and the investigated phages formed a distinct clade within the genus Sp6virus, subfamily Autographivirinae. The genome sequence of phage PM75 was similar to that of a previously described Proteus phage, PM16 [KF319020], and both of them demonstrated low nucleotide sequence identity to the genomes of the other most similar phages, namely, Vibrio phage VP93, Pantoea phage LIMElight, and KP34-like bacteriophages. According to cluster analysis of the complete genome sequences and phylogenetic analysis of the proteins essential for their life cycle, phages PM75 and PM16 are distinct from other similar phages from the phiKMV supergroup and should be recognized as constituting a new genus, "Pm16virus", within the subfamily Autographivirinae.

Enzyme Immunoassay of Antibodies to Endogenous Bioregulators for Evaluating the Risk of Heart Disease.

The levels of natural antibodies to ß-endorphin, bradykinin, histamine, dopamine, and serotonin were measured in 271 cardiological patients in order to evaluate the severity of their clinical status. The patients were distributed into groups differing by the course of the pathological process. The levels of natural antibodies to all antigens were maximum in patients with cardiosclerosis: the content of antibodies to ß-endorphin surpassed the control by 46%, to histamine by 62%, to bradykinin by 36%, to dopamine by 49%, and to serotonin by 65%.

Analysis of immune-biochemical indicators to assess the risk of developing cardiological pathology.

Prognostic immuno-biochemical tests to assess the severity of the condition of patients with cardiac diseases were developed. A comparative analysis of clinical and laboratory blood parameters, which are used in practice for the diagnosis and prognosis of diseases, and an analysis of the content of natural antibodies (n-Abs) to ß-endorphin, bradykinin, histamine, dopamine, and serotonin were performed. A significant correlation between the level of n-Abs, the main biochemical parameters, and the content of blood corpuscles was revealed. The practical importance of the combined use of immunological and biochemical tests to increase the reliability of prediction of the severity of heart pathologies was established.

[A comparative study of immune and clinical indicators in radicular and myofascial back pain]. / Sravnitel'nyi analiz immunokhimicheskikh i klinicheskikh pokazatelei pri dorsalgiiakh koreshkovogo i reflektornogo geneza.

AIM: To compare immunochemical and clinical parameters in patients with chronic radicular and myofascial back pain. MATERIAL AND METHODS: A study included 92 patients (55 men and 37 women) with radicular pain syndrome and 97 patients (33 men and 64 women) with myofascial pain syndrome. Pain status was assessed with the differential visual analogous scale (at rest, on movement, at night and during spontaneous pain). Tensor algometry was used to measure pain intolerance thresholds at day and night. Levels of natural antibodies (nAB) to endogenous pain regulators (ß-endorphin, orphanin, serotonin, dopamine, histamine and angiotensin) were determined in the blood serum by ELISA. Patients were examined at admission to the hospital, on 10th and 21st days of treatment. RESULTS AND CONCLUSION: There was a significant decrease in pain syndrome in all patients to the 21st day. Pain intensity was higher in patients with radicular pain syndrome (р<0.05) in all functional states. Pain intolerance thresholds were initially reduced in both groups. No significant between-group differences in the dynamics were not found either in men or women. Women had lower pain intolerance thresholds compared to men. An analysis of nAB profiles to pain regulators showed that they were correlated with higher and high indices, with the predominance of nAB to ß-endorphin, orphanin and histamine in both groups. The increased levels of antibodies circulate in the blood serum of patients with dorsalgia for a long time can further be a factor of pain chronification.

[The characteristics of morphogenesis of stem cells of hematopoietic organs].

The article presents characteristics of morphogenesis of stem hematopoietic cells at early stages of development. At the same time, analogy is marked concerning morphogenesis of hematopoietic cells in differentiating period of mesenchyme and terminal period of development of bone marrow cells. The role of stem mesenchyme cells in development of hematopoietic cells and elements of their micro-environment is observed.

Lytic bacteriophage PM16 specific for Proteus mirabilis: a novel member of the genus Phikmvvirus.

Lytic Proteus phage PM16, isolated from human faeces, is a novel virus that is specific for Proteus mirabilis cells. Bacteriophage PM16 is characterized by high stability, a short latency period, large burst size and the occurrence of low phage resistance. Phage PM16 was classified as a member of the genus Phikmvvirus on the basis of genome organization, gene synteny, and protein sequences similarities. Within the genus Phikmvvirus, phage PM16 is grouped with Vibrio phage VP93, Pantoea phage LIMElight, Acinetobacter phage Petty, Enterobacter phage phiKDA1, and KP34-like bacteriophages. An investigation of the phage-cell interaction demonstrated that phage PM16 attached to the cell surface, not to the bacterial flagella. The study of P. mirabilis mutant cells obtained during the phage-resistant bacterial cell assay that were resistant to phage PM16 re-infection revealed a non-swarming phenotype, changes in membrane characteristics, and the absence of flagella. Presumably, the resistance of non-swarming P. mirabilis cells to phage PM16 re-infection is determined by changes in membrane macromolecular composition and is associated with the absence of flagella and a non-swarming phenotype.

Pressure algometry and enzyme-linked immunosorbent assay of natural antibodies in the evaluation of pain syndrome.

The dynamics of possible markers of pain syndrome: pain pressure thresholds of intolerance (PTI) and natural antibodies to mediators of pain processing (nAbs) in blood serum at dorsalgia was studied. We have shown that most men and women had reduced PTIs. Night PTIs were lower than daytime PTIs regardless of the gender. The study of the content of nAbs to opioids and biogenic amines by ELISA have shown a prolonged maintenance of their elevated and high levels that could evoke long-term effect in pain chronization. Thus, the pressure algometry and ELISA of nAbs to pain processing mediators make it possible to assess the individual pain status objectively and, on this bases, to propose personal schemes of treatment.

[THE IDENTIFICATION OF SIX CLASSES OF PSYCHOACTIVE SUBSTANCES IN VARIOUS OBJECTS USING TECHNIOUE OF IMMUNE CHROMATOGRAPHY].

The immune chromatographic test-systems were developed to detect psychoactive substances of six classes: opiates, amphetamines, cannabinoids, ecstasy, benzodiasepines, methadone. for the first time the simple techniques of preparation of samples were developed to fast detect the mentioned substances in such biological and non-biological objects as sweat fatty discharges, hair, urine, surface lavages, parts of plants, unknown substances. The presented techniques of preparation and analysis of samples require no special equipment and reagents. They can be applied in the "field" or domestic conditions by laymen for preliminary screening of psychoactive substances.

[Detection of Volatile Organic Compounds Associated with Hepatocellular Carcinoma by Macrosmatic Animals: Approaches to the Search for New Tumor Markers].

Macrosmatic animals (dogs and mice) have been proved to be able to distinguish between the urine or feces of mice with transplanted hepatocellular carcinoma and those of healthy mice by odor. The chemical composition of animal excreta was found to change with tumor growth; however, it is not clear yet if this results from tumor growth itself, inflammation, or immune response. We suggested that the use of the ability of macrosmatic animals to compare odor mixtures combined with mouse cancer models is a promising trend in the search for new tumor markers.

[THE ENERGY FUNCTION OF RAT CARDIAC MITOCHONDRIA UNDER ARTIFICIAL HYPOBIOSIS].

We investigated the energy activity of mitochondria from rat cardiomyocytes under the artificial carbon dioxide hypobiosis, which led to physiological changes in the organism (the decrease of body temperature, the reduction of heart rate, etc.). The respiratory and phosphorylation activities in mitochondria of cardiomyocytes is reduced when using two oxidation substrates (succinate and malate), which characterize the rate of the oxygen consumption by the mitochondria. The partial uncoupling of the oxidation and phosphorylation processes when using the malate unlike succinate was established. The activity of NADH-KoQ-oxidoreductase (complex I of the respiratory chain) is inhibited, but the activities of succinate dehydrogenase and cytochrome oxidase don't change. Probably, the priority of the succinate use under the artificial hypobiosis provides the support of the mitochondria functional activity on a sufficient energy level. It is evidenced by the ATP-synthetase activity. The modifications of the structural and functional state of the inner mitochondria membrane of the cardiomyocytes are directed to the adaptation under the artificial carbon dioxide hypobiosis.

[Dynamics of pain tolerance thresholds and humoral immunity factors at dorsalgy].

OBJECTIVE: Our aim was to study the possible markers of pain syndrome--indicators of pain sensitivity--pain pressure tolerance thresholds (PPTT), and immuno-indicators--natural antibodies against pain processing mediators (eAb) for evaluation the possibility of its using for a objective pain assessment at chronic low back pain. METHODS: Pain sensitivity was assessed daily and nightly, by measuring the PPTT The natural antibody levels (eAb), were determined in serum by ELISA. Measurement of all parameters were performed at 1st, 10th and 21 days. RESULTS: 173 patients (93 women and 80 men) with chronic low back pain were included in the study. At 1st day most patients had lowered PPTT: 55% of men and 74% during the day, 72% of men and 89% of women at night. Dynamic study has shown a tendency of PPTT normalization in men. The study of diurnal PPTT variations have shown that night PPTT lower than day PPTT on 15-17%. We found gender PPTT differences: PPTT values in women 17-26% lower than in men. Analysis of individual eAb profiles has showed that elevated and high levels of eAb to ß-endorphin, orphanin and histamine have 84%, 78%, 84% women and 82%, 85 and 95% men, respectively. These indicators higher than those for serotonin, dopamine and angiotensin (55%, 65%, 70% in women and 65%, 66%, 66% in men, respectively; p < 0.05). Dynamic study of eAb levels have shown a significant anti-histamine eAbs decrease (23%; p = 0.015) only. CONCLUSION: The pathological changes in pain sensitivity and levels of eAbs to pain-processing mediatos are evidenced. Further investigations are necessary to clarify to role of these variations in pain processing and for use these indicators for objective pain assessment.

Oxidative phosphorylation in mitochondria of small-intestinal enterocytes at chronic and single exposure to low power ionizing radiation. / Okysne fosforyljuvannja v mitohondrijah enterocytiv tonkoi' kyshky za hronichnoi' ta razovoi' dii' ionizujuchoi' radiacii' nyz''koi' potuzhnosti.

Objective - to investigate the intensity of oxidation and phosphorylation processes in the small intestine enterocytes mitochondria of the rats under chronic and single exposure to ionizing radiation of low power. Materials and methods. The single irradiation of the rats with X-rays was performed using the RUM-17 equipment (at the dose of 0.055 Gy/min) for absorbed doses of 0.1; 0.5 and 1.0 Gy. The functional state of mitochondria was evaluated in 1 h and 24 h after irradiation. The chronic external γ-irradiation (at the dose rate of 0.72 cGy/min to achieve a total dose of 0.3; 0.6 and 1.0 Gy was performed using the "Etalon" equipment which contained 60Co. The intensity of the oxidation and phosphorylation activity of the small intestine enterocytes mitochondria was assessed by the polarographic method. Results. The use of malate as exogenous substrate allowed to assess the functioning of all areas of the electron transport chain of mitochondria in experimental conditions. The increase in the intensity of mitochondrial respiration was found in all conditions and terms of research in response to irradiation. In chronic ionizing radiation appears partial separation of interface processes of oxidation and phosphorylation, as evidenced by the decrease in value of the index control and ADP / O and reducing efficiency phosphorylation (decrease of value Vf). For single exposure disconnection of coupling processes oxidation and phosphorylation were not accompanied by changes in the index of oxidative phosphorylation, however, was characterized by reduced ratio V4S/V4АТP. Conclusions. Single and chronic exposure to low power of ionizing radiation leads to an increase in intensity of respiration and disruption of oxidative phosphorylation as a result of separation of interface processes of oxidation and phosphorylation. In chronic exposure received changes were accompanied by inhibition of ATP from ADP and FN because no change of ATP hydrolase activity of mitochondria was noticed. The identified functional disruption of enterocytes mitochondria by ionizing radiation may be associated with structural and functional changes of the respiratory chain, activity both enzymes of electron transport chain and H+ -ATPase. Effects of ionizing radiation of low power can lead to disruption of mitochondrial bioenergetic function - one of the earliest manifestations of cellular dysfunction.

[Activity of NAD.H-generating enzymes and cytochrome content in mitochondria from rat liver and myocardium under artificial hypobiosis].

The modification particularities of the structural and functional state of the inner mitochondrial membrane of the rat liver and myocardium were observed in conditions of artificial hypobiosis, which was created using hypoxic and hypercapnic gas medium with a body temperature reduction. Under the artificial hypobiosis the activity of NAD.H-generating enzymes of the Krebs cycle of the liver mitochondria decreases. The established changes of the enzymes activity and cytochromes content of the inner mitochondrial membrane indicate the decrease of the oxidative activity of a respiratory chain, that can be limited on a terminal (cytochrome c oxidase) site and leads to the decrease (by 49% at an average) of the H+-ATPase activity of the liver mitochondria. Under the artificial hypobiosis the detected increase of the succinate-KoQ-oxidoreductase activity (by 65% at average) causes the maintaining of the functional activity of a mitochondrial respiratory chain, considering the high (relative to control) cytochrome c oxidase and H+-ATPase activities of the mitochondria of the rats' myocardium. The structural changes of the inner mitochondrial membrane of the liver and myocardium in experimental conditions are accompanied by the increase of hydrophobicity of tryptophan residues microenvironment and the intramolecular modifications of protein molecules.

[Antibodies to endogenous bioregulators and their association with age and sex in chronic pain syndrome].

Authors studied changes in the levels of antibodies to endogenous bioregulators (Ab) to Β-endorphin, orphanin, serotonin, dopamine and angiotensin in 36 healthy people and 109 patients with dorsopathy with chronic pain syndrome. The association of these immunological indicators with age and sex was found. It has been concluded that the levels of Ab to endogenous bioregulators may be considered as a marker of algic system pathology that does not depend on age and is sex-related.