Immunobiological properties of granulocytemacrophage colony-stimulating factor and synthetic peptides of his active center

Granulocyte-macrophage colony-stimulating factor (GM-CSF) belongs to the group of growth cytokines (hematopoietins) that regulate proliferation and differentiation of myeloid lineage cells. Recently, a lot of new data have accumulated, indicating the presence of a number of previously unknown biological effects in GM-CSF and synthetic peptides of its active center, which open up new prospects for their wide clinical use.The review outlines current understanding of the structure, functions, and mechanisms of GM-CSF action and concerns the structure of its receptor. The GM-CSF producer cells are characterized, as well as target cells (effector cells) responding to this cytokine are also presented. The known mechanisms of intracellular signaling involved into the GM-CSF/receptor interaction are described. The main pleiotropic effects of this cytokine as a factor of hematopoiesis and an immunostimulating agent are characterized. The previously known and recently found immunobiological effects of this cytokine, its recombinant forms and synthetic analogues of its active center are discussed.Participation of GM-CSF in hematopoiesis and differentiation of myeloid cells, the effects of this cytokine on the functional activity of immunocompetent populations (lymphocytes, macrophages, neutrophils, dendritic cells) and tissue cells were characterized. The influence of GM-CSF on the development and course of infectious and inflammatory processes, its role in the creation of combined vaccines is reviewed. Clinical data on usage of GM-CSF and its recombinant forms in hematology, immunology, oncology, reproductive medicine and in the treatment of systemic autoimmune processes and infectious diseases are presented.The recently discovered immunobiological properties of synthetic peptides derived from active center of GM-CSF are summarized, indicating that they exhibit immunotropic and hematopoietic effects, as well as antimicrobial activity against Gram-negative and Gram-positive bacteria, viruses, and tissue repair (effect on the rate of wound healing), which is not typical to the whole GM-CSF molecule. We discuss the prospects for clinical applications of synthetic GM-CSF analogue (ZP2 peptide), and an opportunity of creating new cosmetics and pharmaceuticals with combined immunostimulating, antimicrobial and reparative properties on its basis.The review expands the view on potential usage of cytokine therapy in the treatment of various infectious and non-infectious diseases in humans, and is addressing a wide range of specialists working in the field of allergology and immunology, infectology and regenerative medicine

Sex differences of subpopulation composition of lymphocytes in the peripheral blood in experimental acute and chronic ulcerative colitis

We studied sex differences lymphocytes subpopulations of peripheral blood in adult C57Bl/6 mice during acute and chronic colitis, induced with 1% DSS. We measured subpopulations of lymphocytes with flow cytometry. We showed that in the control group the female mice had statistically significantly higher values of the relative number of regulatory and cytotoxic T lymphocytes comparing to the males. During acute colitis the females showed an increase in the relative number of Thelpers and a decrease of cytotoxic Tlymphocytes, which reflects the activation of immune response. The males had a decrease in the absolute number of leukocytes, lymphocytes and cytotoxic and regulatory T lymphocytes, probably because of an increase in migration of these cells to the inflammation locus and local lymph nodes. In chronic colitis the females had a decrease in the absolute number of leukocytes, lymphocytes, T helpers, cytotoxic T lymphocytes and B lymphocytes when comparing with acute colitis. During chronic colitis the males had a decrease in the absolute number of T helpers and B lymphocytes but an increase of regulatory T cells in comparison with the control group; in comparison with acute colitis the males with chronic colitis had higher relative and absolute number of regulatory T cells. The increase of T regulatory lymphocytes is due to an increase in their proliferation rate in the thymus and increase of their migration to the inflammatory locus – the colon. Future clinical studies may be based on these results, which show that the treatment of colitis, especially with immunotropic agents, must take sex differences into account

Recurrent versus first cervical artery dissection - a retrospective study of clinical and vascular characteristics

Background and purpose Most recurrent cervical artery dissection (CeAD) events occur shortly after the acute first CeAD. This study compared the characteristics of recurrent and first CeAD events and searched for associations between subsequent events of an individual person. Methods Cervical artery dissection patients with a new CeAD event occurring during a 3-6 month follow-up were retrospectively selected in seven specialized stroke centers. Clinical and vascular characteristics of the initial and the recurrent CeADs were compared. Results The study sample included 76 patients. Recurrent CeADs were occlusive in one (1.3%) patient, caused cerebral ischaemia in 13 (17.1%) and were asymptomatic in 39 (51.3%) patients, compared to 29 (38.2%) occlusive, 42 (55.3%) ischaemic and no asymptomatic first CeAD events. In 52 (68.4%) patients, recurrent dissections affected both internal carotid arteries or both vertebral arteries, whilst 24 (31.6%) patients had subsequent dissections in both types of artery. Twelve (28.6%) of 42 patients with an ischaemic first dissection had ischaemic symptoms due to the recurrent CeADs, too. However, only one (1.3%) of 34 patients with a non-ischaemic first CeAD suffered ischaemia upon recurrence. Conclusion Recurrent CeAD typically affects the same site of artery. It causes ischaemic events less often than the first CeAD. The risk that patients who presented with solely non-ischaemic symptoms of a first CeAD will have ischaemic symptoms in the case of a recurrent CeAD seems very small.Peer reviewe

XXVI ВСЕРОССИЙСКАЯ МОЛОДЕЖНАЯ КОНФЕРЕНЦИЯ «СТРОЕНИЕ ЛИТОСФЕРЫ И ГЕОДИНАМИКА», ИРКУТСК, РОССИЯ, 20–25 АПРЕЛЯ 2015 Г.

The report presents a chronicle of the XXVI All-Russia youth conference “Lithosphere structure and Geodynamics”, dedicated to the 85th anniversary of academician Nikolai A. Logachev – outstanding geologist, specialist on the continental rifting. The major events are highlighted and a thematic review of the conference papers is given.В сообщении представлена хроника проведения XXVI Всероссийской молодежной конференции «Строение литосферы и геодинамика», посвященной 85-летию со дня рождения академика Николая Алексеевича Логачева – выдающегося геолога, специалиста по континентальному рифтогенезу. Освещены основные события и дан тематический обзор докладов конференции

Дизайн и синтез гидрофобных производных RGD-пептидов

Hydrophobic peptide derivatives containing RGD-amino acids sequence have been synthesized and ability of cationic liposomes to form complexes with DNA has been investigated.Осуществлен синтез гидрофобных производных RGD- и RGDS-пептидов и исследована способность катионных липосом с их включением образовывать комплексы с ДНК

Clinical diagnostic criteria of efficiency for combined etiopathogenetic therapy in patients with chronic Epstein–Barr virus infection

Treatment of chronic viral infections accompanied by permanent virus persistence in the target epitopes of the oral cavity, skin, urogenital tract is complicated by virtual lack of available drugs exerting combined systemic virulicidal and immunomodulatory effects. Here we demonstrate clinical and immunological efficacy of combined therapy in treatment of Epstein–Barr virus (EBV)-associated chronic infections. The aim of the study was to evaluate the clinical and immunological efficacy of combined etiopathogenetic therapy using the Acegram cosmetic product in patients with EBV-associated chronic infections. Materials and methods. There were enrolled 40 patients monitored before treatment as well as 20 patients followed up after combination therapy (cycle therapy consisted of oral valaciclovir (Valtrex) applied at dose of 500 μg twice a day for 10 days, glucosaminylmuramyldipeptide (Licopid) — 10 mg 2 twice a day for 10 days, topical irrigation for mucous membranes with granulocyte-macrophage colony-stimulating factor active center-derived peptide (Acegram-spray) 3 times a day for 10 days. If necessary, treatment courses were repeated 20 days after the onset. All patients were examined for the presence of EBV genomes in the oral fluid and blood using the qualitative and quantitative polymerase chain reaction (PCR) using the DNA technology test system (Russia) on a DT-Lite device prior treatment and 30, 60 days post-therapy time points. In addition, serum samples were analyzed for level of class G immunoglobulins specific to the EBV nuclear and capsid antigens by using enzyme immunoassay (test systems manufactured by CJSC Vector Best, Russia) as well as immune status (clinical methods, enu flow cytometry evaluation of the phagocytic activity of neutrophils, ELISA method). Results. Use of single or two course combination therapy in subjects with fully eradicated EBV carriage associated with reversed clinical symptoms was accompanied by recovered immune system status (T and B cells, T-helper cells, CD3+ CD25+  cells, phagocytosis parameters). A non-invasive approach proposed for controlling virus elimination in the oral fluid by using polymerase chain reaction method may serve as to objectively monitor therapeutic efficacy

Biochemical markers of neurodegeneration in patients with cerebral small vessel disease and Alzheimer's disease

Introduction. Cerebral small vessel disease (CSVD) as well as the Alzheimer's disease (AD) and their comorbidities are the most common causes of cognitive impairments (CIs). Objective: to evaluate the predictive power of the biochemical neurodegeneration markers in patients with CSVD and AD. Materials and methods. We assessed the following neurodegeneration markers in 68 patients with CSVD (61.0 8.6 years; 60.3% males), 17 patients with AD (65.2 8.3 years; 35.3% males), and 26 healthy volunteers (59.9 6.7 years; 38.5% males): neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), neurofilament light polypeptide (NEFL) in blood (for all patients) and in cerebrospinal fluid (CSF; in patients with CSVD and AD). We assessed the predictive power of those markers with ROC analysis. Results. As compared to the control group, serum GFAP in patients with CSVD showed its predictive power at 0.155 ng/ml (sensitivity 74%; specificity 70%). Serum NEFL 0.0185 ng/ml (sensitivity 82%; specificity 96%) and NSE 4.95 g/ml (sensitivity 77%; specificity 71%) showed their predictive power in patients with AD. CSF GFAP 1.03 ng/ml (sensitivity 84%; specificity 88%), CSF NSE 19.10 g/ml (sensitivity 88%; specificity 91%), serum NEFL 0.021 ng/ml (sensitivity 71%; specificity 76%), serum NSE /CSF NSE ratio 0.273 ng/ml (sensitivity 87%; specificity 88%) help differentiate CSVD from AD. Conclusions. We found that serum GFAP can be a useful diagnostic marker in patients with CSVD, while serum NEFL and serum NSE can help identify the AD. In addition, CSF GFAP and CSF NSE as well as serum NEFL and serum NSE/CSF NSE can help differentiate CSVD from AD. We can use those markers in clinical and research practice to identify the vascular and neurodegenerative causes of CIs and their comorbidities, which is of a great importance in developing specific treatment and predicting the course of the disease

Post-COVID immunopatology syndrome: characteristics of phenotypical changes in the immune system in post-COVID patients

This study examines the long-term effects of SARS-CoV-2 infection on immune status. Given the prolonged and profound immune dysregulation observed during acute SARS-CoV-2 infection, it remains to be determined whether these changes translate into subsequent immune system dysfunction in recovering individuals. In this sense, the aim of the study was to study the parameters of the immune system in patients who had undergone SARS-CoV-2 infection. 150 patients who underwent SARS-CoV-2 infection were examined according to 96 parameters using flow cytometry. A complete blood count was performed using a Medonic device (Sweden); ELISA method determined the levels of general and specific IgM, IgG, IgA, compliment fragments (JSC Vector-Best, Russia). The activity of the phagocytes was studied according to the generally accepted method. The study found that at least four phenotypes of immune system disorders are detected in patients. The first two phenotypes are related to the impairment of innate immune system factors and are associated with a decrease in the number of CD46+ and NK cells. It has been observed that a decrease in CD46+ persists for a long time in a significant number of recovered patients, highlighted by the impaired expression of this marker in various subpopulations of lymphocytes. The decrease in the level of natural killers was accompanied by a compensatory increase in the number of T lymphocytes, mainly due to T helpers and TNK lymphocytes, and the growth of total memory B cells. Two other identified phenotypes are characterized by damage to acquired immune response factors and are associated with damage to B cells and T cytotoxic cells. The relationship of such disorders with damage to hematopoiesis erythrocyte and platelet sprouts, which contribute to the appearance of hypoxia and possible violation of the blood coagulation system, has been shown. Therefore, the results obtained indicate a long-term pronounced damage to the immune system in postCOVID patients that requires immunocorrection of these disorders

Возможность использования диквертина для лечения остеоартроза в гериатрической практике

Complex treatment of aged and old patients ( n = 60) suffering from deforming osteoarthrosis complicated with reactive synovitis in combination with associated pathology of cardiovascular system is studied. Natural antioxidant dicvertase introduced by ultrasonic waves was used. Positive combined action of ultraphonophoresis by dicvertase was revealed which resulted in lowering pain syndrome, increasing motions range in the affected joint, normalizing of immunity status which allows to broaden indications for the treatment of these patients by lowering the risk of development of pathologic response of the organism on the treatment and facilitates lowering drug loading on patients.Изучена возможность комплексного лечения больных деформирующим остеоартрозом, в том числе осложненным реактивным синовитом, пожилого и старческого возраста (60 пациентов) в сочетании с сопутствующей патологией сердечно-сосудистой системы с использованием природного антиокcиданта диквертина, вводимого ультразвуковыми волнами. Выявлено положительное сочетанное действие ультрафонофореза диквертина, проявившееся в уменьшении болевого синдрома, увеличении объема движений в пораженном суставе, нормализации иммунного статуса, что позволяет расширить показания для лечения этой группы больных, уменьшая риск развития патологической ответной реакции организма на лечение, и способствует снижению медикаментозной нагрузки на пациентов

Pilot Project «All-Russian Registry of Patients with Severe Bronchial Asthma.» The First Results in a Children’s Group of Patients (Moscow’s Observation Program)

The article presents the first results of the pilot observation program «The All-Russian Severe Asthma Patient Registry» which was started in Moscow. Objectives. The objective of this initiative is the accumulation of clinical data on patients with severe bronchial asthma in the Russian Federation. Methods. The chosen method was a registry, the rights holders of which were 3 professional associations — Interregional Public Organization «Russian Respiratory Society», Public Organization «Union of Pediatricians of Russia», All-Russian Public Organization «Association of Allergologists and Clinical Immunologists». Results. The results of the pilot project are presented by the data analysis of electronic case report forms of 36 children (totally, the project included 100 patients, 64 adults and 36 children) enrolled in the program from June to December 2016. Using the registry, a detailed analysis of the clinical characteristics of a group of children with severe atopic bronchial asthma was carried out, the results of a pharmacoepidemiological evaluation of therapy were given. Obtained by the researchers, a high frequency of the assignment of a genetically engineered biologic drug of omalizumab meets the international recommendations but does not reflect the all-Russian reality and can be explained by inclusion in the registry of pediatric patients observed only in the Federal State Autonomous Institution «National Scientific and Practical Center of Children’s Health» of the Ministry of Health of the Russian Federation. Conclusion. To determine true indicators that characterize bronchial asthma in children in the Russian Federation it is necessary, undoubtedly, to expand the geography of project participants