Репозиторий Университета

© 2018 Dynasty Publishing House. All rights reserved. Exosomes (vesicles with the size of 30-150 nm) are formed in multivesicular bodies (MVB) by invagination of early endosome membranes and mediate intercellular interactions. Exosomes are secreted by various kinds of cells, their content might be represented by proteins, lipids and nucleic acids, which reflect the functional state of donor cells. The effect of exosomes on recipient cells depends on their quantity and characteristics of their «load». Comparatively recently, placental exosomes secreted by various placental cells have been isolated from blood of pregnant women. A specific protein - placental alkaline phosphatase (PLAP) - has been determined for these exosomes. PLAP-positive exosomes can be found in maternal blood as soon as in the first trimester of pregnancy, their number increases with maturation of the foetus and reaches its maximum by the moment of birth. Although the functional significance of placental exosomes is still investigated, some authors relate changes in the placental exosome profile (their number and composition) to placental dysfunction underlying the development of complications of pregnancy. Isolation of exosomes from blood of pregnant women (fluid biopsy) and determination of their biological characteristics might be regarded as early noninvasive diagnosis of structural and functional placental abnormalities. The appearing evidence of blastocyst-secreted exosomes and their role in modulating maternal immunity and endometrial receptiveness during implantation are also promising. The review presents data about the biogenesis, structure and functions of exosomes and the role of placenta-associated exosomes in the development of physiological and complicated pregnancy, and also about the possibility of using exosomes as a marker of the state of the blastocyst in assisted reproductive technologies, in particular, in oocyte donation and surrogate motherhood.

© 2018, Media Sphera Publishing Group. All rights reserved. The article addresses gait disturbances in the elderly. It emphasizes that the system that maintains the balance in resting conditions and gait is based on the hierarchical principle and its function depends on the maintenance of integration between vestibular, visual and somatosensory information as well as on cognitive functions. Walking depends on the integrity of frontal-subcortical neuronal circles that support regulatory functions. The main pathogenetic mechanisms of age-related disturbances of balance and gait are a decrease in the efficacy of spinal motorneurons activation caused by Ia-afferentation, a decrease in cortical activation and excitability of corticospinal pathways and in the intensity of intracortical inhibition. The causes of age-related changes in walking are not confined to a single system (e.g., one sensory modality) but have a multisystem character and are involved in many structures. The author analyses the results of recent studies that use functional neuroimaging methods.

© 2018 Russian Electronic Journal of Radiology. All Rights Reserved. Purpose. The purpose of this study was to determine possibilities of functional computed tomography for diagnostics of the knee endoprosthesis loosening. Materials and methods. A total of 12 patients with suspected knee endoprosthesis loosening were observed. We performed dynamic computed tomography on the Toshiba Aquilion One 640. On MIP images in the three planes of the joint in the static position, we marked up to 5 lines. Every line connected the point in prosthesis component with the point in the periprosthetic cortical bone. After that, the computer analysed the functional research reconstruction and showed the length of the same lines at each stage of knee flexion. If the length of at least one of the lines changes by more than 1.1 mm, we can confirm loosening of the endoprosthesis component. Results. According to data of dynamic computed tomography, in 2 patients we identified loosening of the tibial components, 1 patient – the loosening of the femoral component and 1 patient – the loosening of both components. In 8 patients knee implants were stable. In 10 patients we performed total revision knee arthroplasty. Computed tomography data were fully confirmed by intraoperative examinations. 4 patients were operated because of components loosening, 6 patients were operated because of patellofemoral in-congruence. 2 patients were treated conservatively with good results. Conclusion. The dynamic computed tomography of the knee after total arthroplasty showed high efficiency in diagnostics of the knee endoprosthesis loosening.

© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: Complications after hip/knee/other joint arthroplasty develop in approximately 1-1.5% of young people and in 2.5-3% of elderly patients. Despite the meager chance of developing negative consequences, they can affect anyone, especially those who did not follow the rigorous rehabilitation program. Complications after endoprosthetics of hip/knee/other joints results from incorrect postoperative care and physical activity after discharge from the hospital. The second reason is technical approach of the surgeon. And third is an inadequate preoperative examination. The aim of the article is to have a detailed description of short term, midterm and long-term complications after joint replacement surgeries and of the methods (clinical and radiological) to avoid those complications with all the required parameters.

© 2018 Medical Education. All rights reserved. The aim of the study was to investigate an efficacy of short-term treatment with acetazolamide (ACET) in patients with acute exacerbation of COPD (AECOPD) and noninvasive ventilation (NIV). Methods. This was a prospective case-control study. The study involved 20 patients. Inclusion criteria were as follows: AECOPD; pH > 7.33; PaCO2 > 48 mmHg; HCO3 - > 26 mmol/L; and treatment with NIV. Clinical characteristics, Charlson comorbidity index, APACHE II score, arterial blood gases, and serum electrolytes were recorded before inclusion. Patients were defined as cases when they had received ACET (500 mg per day) for 3 days; they were compared to a matched control group who did not receive ACET. Clinical parameters, arterial blood gases, serum electrolytes, potential adverse effects, and length of hospital stay were monitored daily. Results. No significant differences in baseline characteristics, comorbidities, or concomitant drugs used were found between the groups. Mean duration of hospital stay was significantly shorter in the ACET group (16.2 ± 8.4 days vs 19.1 ± 2.8 days; p = 0.023). An iIntra-group analysis showed a significant improvement in clinical and arterial blood gas parameters in both groups already in the first day of the treatment. In the ACET group, systolic blood pressure (SBP), respiratory rate (RR), and SpO2 significantly improved at day 4 (112.5 ± 4.9 mmHg vs 125 ± 7.1 mmHg (p = 0.001); 15.2 ± 1.1 min-1 vs 17.1 ± 0.9 min-1 (p = 0.001) and 94.7 ± 1.1% vs 92.3 ± 0.8% (p = 0.0001), respectively). There was a significant decrease in PaCO2, pH and HCO3- at day 3 (48 ± 3.8 mmHg vs 52.4 ± 5.3 mmHg (p = 0.0288); 7.374 ± 0.4 vs 7.502 ± 0.17 (p = 0.0015) and 26.4 ± 2.8 mmol/L vs 36.9 ± 4.1 mmol/L (p = 0.00001), respectively) and day 4 (44 ± 2.4 mmHg vs 48.4 ± 4.6 mmHg (p = 0.0115); 7.387 ± 0.02 vs 7.480 ± 0.02 (p = 0.00001) and 24.2 ± 2.1 mmol/L vs 35.6 ± 3.0 mmol/L (p = 0.00001), respectively) in the ACET group. No adverse events were recorded in both groups. Conclusions. ACET adjuvant to NIV appears to be effective and could prevent post-NIV alkalosis occurrence and could reduce the length of hospital stay in patients with AECOPD and mixed metabolic disorders (respiratory acidosis and metabolic alkalosis).

Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Monanchomycalin B and urupocidin A were isolated from the marine sponge Monanchora pulchra. We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but are inactive against the TRPA1 receptor. Monanchomycalin B is the most active among all published marine alkaloids (EC50 6.02, 2.84, and 3.25 μM for TRPV1, TRPV2, and TRPV3, correspondingly). Moreover, monanchomycalin B and urupocidin A are the first samples of marine alkaloids affecting the TRPV2 receptor. Two semi-synthetic urupocidin A derivatives were also obtained and tested against TRP (Transient Receptor Potential) receptors that allowed us to collect some data concerning the structure-activity relationship in this series of compounds. We showed that the removal of one of three side chains or double bonds in the other side chains in urupocidin A led to a decrease of the inhibitory activities. New ligands specific to the TRPV subfamily may be useful for the design of medicines as in the study of TRP channels biology.

The discovery and development of effective antihypoxic drugs is an important issue in modern experimental and clinical pharmacology. Complexes of zinc containing imidazole cycles as ligands are promising candidates for the design of novel drugs, including pharmacotherapeutic tools for patient’s protection under conditions of oxygen deficiency. Herein, we report antihypoxic activity of zinc complexes with N-alkenylimidazoles, and, specifically, a novel drug Acyzol, which can be used as efficient antidote after poisoning by carbon monoxide and other combustion products.

Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies. View Full-Text

Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies. View Full-Text

Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Monanchomycalin B and urupocidin A were isolated from the marine sponge Monanchora pulchra. We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but are inactive against the TRPA1 receptor. Monanchomycalin B is the most active among all published marine alkaloids (EC50 6.02, 2.84, and 3.25 μM for TRPV1, TRPV2, and TRPV3, correspondingly). Moreover, monanchomycalin B and urupocidin A are the first samples of marine alkaloids affecting the TRPV2 receptor. Two semi-synthetic urupocidin A derivatives were also obtained and tested against TRP (Transient Receptor Potential) receptors that allowed us to collect some data concerning the structure-activity relationship in this series of compounds. We showed that the removal of one of three side chains or double bonds in the other side chains in urupocidin A led to a decrease of the inhibitory activities. New ligands specific to the TRPV subfamily may be useful for the design of medicines as in the study of TRP channels biology.

The discovery and development of effective antihypoxic drugs is an important issue in modern experimental and clinical pharmacology. Complexes of zinc containing imidazole cycles as ligands are promising candidates for the design of novel drugs, including pharmacotherapeutic tools for patient’s protection under conditions of oxygen deficiency. Herein, we report antihypoxic activity of zinc complexes with N-alkenylimidazoles, and, specifically, a novel drug Acyzol, which can be used as efficient antidote after poisoning by carbon monoxide and other combustion products.