L-homoarginine (hArg) is a non-coding amino acid, the blood level reduction of which is associated with an increased risk of stroke and heart attack. In humans and animals, hArg is mainly formed during the reaction catalyzed by the enzyme of the metabolic pathway of creatine biosynthesis:arginine: glycine amidotransferase (AGAT, EC 2.1.4.1), in the case where L-lysine acts instead of glycine as an acceptor of the arginine amidine group. It has been shown that hArg can serve for nitric oxide biosynthesis which is seemed a single significant enzymatic pathway established for hArg.

The aim of this study was to investigate hArg as a substrate human AGAT and arginases.

Materials and methods. In experiments with recombinant enzymes we established that Km for hArg in the reaction catalyzed by AGAT towards the formation of guanidinoacetic acid is 12.0 ± 1.1 mM. In reactions catalyzed by both types of arginase activity against hArg, unlike arginine, was not detected.

Conclusions. Thus, the present study established that hArg may be considered as a substrate of AGAT additionally to nitric oxide synthases. Metabolic value of hArg, in addition to regulation of vascular tone, can be associated with cell energy metabolism. According to our data a decrease of hArg blood levels in cardiovascular diseases appears to be unrelated to a detectable increase of arginase activity.

Despite a broad discussion of the results of ultrasound in Parkinson disease, the dynamics of hyperechoinality of the substantia nigra based on the clinical forms and stages of the disease remains controversial.

The purpose of this study is to study thechanges in the substantia nigra of the brain based on the clinical form and stage using an ultrasound in patients with Parkinson’s disease.

Materials and methods. The study involved 100 patients with Parkinson’s disease whom were scanned using transcranial sonography through the temporal window with the use of ultrasound scanner Toshiba Aplio 500 (Japan) with a sector transducer with a frequency of 2,5 мGz.

Results. It was found that the asymmetric variant of changes in the black substance prevailed in each clinical group of patients and was more often recorded with akinetic-rigid form and the greatest changes were observed in the stages  II and III of the disease. 

The goal is to reveal features of changes in the ratio of cytokines IL-1β, IL-6, TNF-α and IL-10 in blood depending on polymorphism of genes IL1В, IL6, TNFА and IL10 at different clinical forms of chronic inflammation of the middle ear in the stage of exacerbation before treatment and on the 10th day of treatment.

Materials and methods. A total of 299 patients (129 men and 170 women) with chronic purulent otitis media were examined: 146 with tubotympanic form and 153 with epitympanoantral form. The control group included 183 relatively healthy donors, comparable to those of 299 patients by sex and age. Human genomic DNA was isolated from the blood by a standard method and was analyzed with the use of the polymerase chain reaction (PCR) in real-time. The concentration of cytokines IL-1β, IL-6, TNF-α and IL-10 in blood was measured by solid-phase enzyme-linked assay before and after 10 days of treatment. Statistical processing of the obtained data was performed using software package STATISTICA 6.0 (StatSoft Inc., USA). The critical level of significance when testing statistical hypotheses was taken to be less than 0.05.

Results. In patients with chronic purulent otitis media, an increase in the concentration of IL-1β, IL-6 and TNF-α in the blood varies depending on polymorphism of genes IL1В (-3953, -511, -31), IL6 (-174), TNFА (-308) and the clinical form of the disease. The concentration of IL-10 in the blood depends more on the polymorphism of the IL10 gene (-1082, -592) than on the clinical form of the disease. The combined increase of concentration of IL-10 and proinflammatory cytokines in the blood before the beginning and on the 10th day of combined treatment of patients with tubotympanic and epitympanoantral forms of chronic purulent otitis media, in carriers of high-producing alleles inflammatory cytokines of polymorphic variants of genes IL1B, IL6 and TNFA, indicates a genetic predisposition to hyperergic the course of inflammation.

The influence of various environmental factors indirectly, through the epigenetic mechanisms of regulation of gene expression, can lead to the activation of human endogenous retroviruses. The purpose of this study was to investigate the possibility of activation of the first class HERV-E λ 4-1 (ER λ 4-1) endogenous retrovirus as a result of exposure to UV radiation in vitro.

Materials and methods. Blood mononuclear cells (MNCs) of conditionally healthy individuals in a concentration of 20 x 106/ml were exposed to UV irradiation for 5 minutes on an ultraviolet radiator at a wavelength of 340 nm and a radiation intensity of 50 W/m2 in vitro. After irradiation, the cell samples were cultured for 24 hours in a complete culture medium in a CO2 incubator. Then, in these cell culture samples the proliferative activity, based on the incorporation of tritium labeled thymidine, a viability, by the trypan blue staining, and ER-E λ 4-1 expression by the reverse transcriptase polymerase chain reaction method, were determined.

The main results. UV irradiation of mononuclear cell cultures for 5 minutes did not leads to the changes in their viability and functional activity. The study of the of the env ER λ 4-1 gene expression frequency in the MNC of donor’s blood before and after the exposure to UV radiation revealed the differences in this index. Thus, before the exposure to UV radiation, the expression rate of env ER-λ 4-1 was 4.4% (2/45), whereas after the irradiation its expression was determined much more often  24% (11/45). Along with an increase in the expression frequency, an augmentation in the mRNA level of the env gene ER-λ 4-1  was also observed.

Conclusion. Thus, the exposure to ultraviolet radiation with the intensity of 50 W/m2 for 5 minutes on blood mononuclear cells of conditionally healthy individuals in vitro leads to activation of the human endogenous retrovirus HERV-E λ 4-1: an increase of its expression frequency and the level of mRNA. 

Brain malformations are one of the most frequent causes of epilepsy in childhood. In patients with malformations of the brain epilepsy is diagnosed in 75–80% of cases. Lissencephaly is a cortical malformation, which develops as a result of global violations of glial-neuronal migration. The probable cause of the deterioration is considered to be the “Transportation” function-specific astrocytes and radial glial fibers involved in the migration of germ cells. The absence of convolutions in the mature brain – morphological substrate is agyria full lissencephaly, the presence of only a single, rudimentary and thickened gyri (pachygyria) – incomplete lissencephaly. Clinical manifestations lissencephaly presented delayed psycho-motor development, spastic tetraplegia and intractable epilepsy.

Materials and methods. To examine and compare the clinical, electrophysiological and neuroimaging results in children with symptomatic epilepsy with lissencephaly, to assess the effectiveness of antiepileptic therapy and to identify the frequency of drug-resistant forms of epilepsy. The study involved 22 patients with lissencephaly. In all the children studied anamnesis and neurological examinations were conducted and neuroimaging and electrophysiological studies were performed.

Results. In neuroimaging examinations, pachygyria and agyria were equally identified. The preferential localization pachygyria was observed in the frontal region. In most cases, clinical examination revealed the presence of motor deficits, cognitive and behavioral disorders. The debut of seizures was observed significantly more often in the age of six months. In general, during the observation period focal seizures with secondary generalization like, with or without secondary generalization were more common. Neuroimaging and EEG correlation was noted in half of the children surveyed.

Conclusions. In the treatment of epileptic seizures in patients valproate are used more often. The results of the study suggest that one of the common causes of severe forms of epilepsy in children is malformations of brain development, so their early diagnosis and adequate antiepileptic therapy correlated with the prevention pharmacoresistance, symptomatic epilepsy and disability in children.

Purpose. To evaluate a morphofunctional state of the epithelial cells of the acini and ducts of submandibular glands of mature rats after repeated incisors amputation.

Materials and methods. The experiment was performed on mature (2 months) white male rats, divided into groups: intact, control group and a group of rats subjected to repeated incisors amputation. Applying histological, histochemical and morphometric methods, we evaluated the morphological and functional state of the epithelial cells in submandibular glands of adult rats at 2, 3, 4, 6, 8, 10 and 12 weeks after repeated amputation of the incisor teeth.

Results. There is an increase of submandibular gland acini area at the 3–10 week after repeated incisors amputation. The functional activity of the submandibular glands ducts and acini cells decreases at the 2–4 week of the experiment.

Conclusion. As a result of repeated incisors amputation in rat submandibular glands acini and ducts epithelial cells develop reversible structural and functional changes, which are leveled by the 12th and 6th week of the experiment, respectively.

Aim. The study was aimed at detailed description of the technique of bariatric surgical interventions with varying metabolic effects in the rat. We also provided comparison between different surgical operations and considered rationale for making several types of surgery simultaneously.

Materials and мethods. The study was performed on 120 male Wistar rats (380–510 g) housed in the SPF rodent facility. The animals were anesthetized using isoflurane anesthesia. The following types of surgery were performed and described: sleeve gastrectomy, gastric bypass, gastrojejunal bypass, ileal transposition, and combination of sleeve gastrectomy and ileal transposition. The technical complexity of surgery was scored according to 10-point scale.

Results. The methodological aspects of sleeve gastrectomy, gastric bypass, gastrojejunal bypass, and ileal transposition in rats are considered in detail. Sleeve gastrectomy and gastric bypass are the most commonly used types of bariatric surgery, while gastrojejunal bypass and ileal transposition are specifically aimed at modeling of metabolic effects. The article considered preoperative planning as well as major stages of surgery. We focused attention on perioperative complications and technical nuances.

Conclusion. Modeling of bariatric surgical interventions on the small laboratory rodents is challenging, requires sophisticated manual skills and microsurgical equipment. The illustrated description of these surgical interventions will provide a useful reference for beginners in this laborious part of experimental surgery. 

Objective. To study the dose-dependent effect of simvastatin on the change of content of individual fatty acids (FA) profile of blood serum and their complexes with secondary prevention of chronic coronary heart disease (CHD) in groups of men and women.

Materials and methods. Gas-liquid chromatography-mass spectrometry was used to establish the absolute and relative levels of FA in serum of 155 CHD patients before and after treatment by simvastatin in doses of 40 mg (89 people) and 80 mg (36 people).

Results. The statin lowered the content of the FA proportionally by reducing the unsaturated (UFA), mainly polyunsaturated (PUFA) FA, and saturated (SFA) FA. The level of monounsaturated fatty acids (MUFA) decreased in women at a dose of 40 mg. The statin increased endogenous formation of ω6 PUFA, ω9 MUFA, and SFA even (except 80 mg), in group of women (40 mg) – ω3 PUFA, and in men (80 mg) – ω7 MUFA. In women after receiving simvastatin 80 mg, the ratio ω3/ω6 PUFA has been shifted to ω6 PUFA, but in men after receiving simvastatin 40 mg in the direction of ω3 PUFA. Only the dose of 80 mg shifted the ratio of C20:5/C20:4 in the direction of ω3 PUFA. In group of women after receiving simvastatin 40 mg was observed a shift to β-oxidation of C18:1(9), and in men at the dose of 80 mg in the direction of its synthesis. In all cases, increased antioxidant protection of PUFA, but less strong it was at the dose of 40 mg. At the same time the formation of MUFA prevailed over the synthesis of SFA. Absolute content of FA - substrates of energy decreased. In all cases, was noticed the decrease of content of FA this very long chain (C22-26), stronger in women.

Conclusion. Simvastatin controlling the quantitative composition of the pool of circulating lipoproteins, FA and cholesterol, is ambiguous, depending on dose, affect the metabolism of fatty acids, changing their quantitative and qualitative composition and performing biological functions.

Aim. To evaluate venous thromboembolic complication risk in elderly patients admitted to trauma and orthopedics departments, prevalence of comorbidity, its impact on the risk of thrombotic events, efficacy and safety of prophylactic anticoagulant therapy.

Materials and methods. Authors performed a retrospective analysis of medical records of 120 patients aged 65 years and over. Analyzed data included demographic data, main diagnosis, co-existing pathology according to International Classification of Diseases X, type of surgery and anticoagulant prophylaxis. Risk of development of venous thromboembolic complications was assessed by the Caprini scale. Potential drug-drug interactions were checked using Drug Interaction Checker available, created by company Cerner Multum according to FDA recommendations.

Results. The most frequent causes of hospitalization were destructive large joint arthritis (40%) and fractures of lower extremities (21.7%). Surgeries with an average duration of 87 ± 31.4 min were performed in 85% of patients, of which major surgery – 68.6%, minor – 31.4%. Comorbidity was detected in 90% of elderly patients admitted to hospital because of pathology of the musculoskeletal system. Pathology of musculoskeletal system most often was combined with cardiovascular diseases (81.7%). A moderate risk of venous thromboembolic complications was detected in 10% patients, high risk in 75%. Anticoagulant prophylaxis with a direct factor Xa inhibitor rivaroxaban or low-molecular weight heparin enoxaparine sodium was performed in 80% of patients.

Conclusion. The study demonstrated that 75% of elderly patients with pathology of the musculoskeletal system are at high risk for the development of venous thromboembolic complications. The main risk factors include the type and duration of surgery and comorbidity.

Objective: evaluate the effectiveness of treatment of retinal vein occlusion with the use of “massage” of retinal veins on the experimental model of photoinduced retinal venous occlusive disease.

Materials and methods. Studies were carried out on 30 rabbits of the Chinchilla breed (30 eyes) weighing 1.5–2.0 kg. In the first stage of the experiment, for all animals the photoinduced thrombosis were modeled by laser irradiation of its retinal veins for 0.3–0.4 seconds at a density of 200 J/cm2 and a wavelength of 662 nm after the administration of “Photoditazine” at a dose of 2.5 mg/kg weight. In the second stage of the experiment, the animals were divided into the main group and the comparison group, depending on the method of treatment: 15 animals of the main group with “massage” of the retinal vein in the form of 5–7 movements with a silicone tip of the scanner Tano, 15 animals of the comparison group with epiretinal administration of recombinant prourokinase in a dose 500 international units (IU).

Results. The formation of a parietal thrombus in the simulation of photoinduced the central retinal vein occlusion in the experiment leads to a slowing of perfusion in the affected vessel by (8.0 ± 2.5) s (according to fluorescence angiography), an increase in the thickness of the central parts of the retina by (70.2 ± 9.7) μm (according to optical coherence tomography), to the appearance of crimp and uneven lumen of the retina veins, extensive plasma and hemorrhages (according to the data of ophthalmoscopy). On the model of retinal veins thrombosis, a new method of treating retinal vein occlusion was tested, which showed significant efficacy. It has been established that the use of “massage” of the affected retinal vein reduces the time of venous perfusion by 1.3 times and 1.45 times accelerates the resorption of the edema of the central parts of the retina compared to enzymatic thrombolysis.

Conclusions. “Massage” of the retinal veins is an effective method of treating retinal vein occlusion and is not accompanied by damage to chorioretinal structures during manipulation.

Search and synthesis of glucose derivatives for nuclear medicine is of great current interest. Being a promising analogue of glucose, D-glucosamine iodine labeled glucose derivatives can be applied in rheumatoid arthritis radionuclide diagnostics and therapy as a radiopharmaceutical.

The purpose of the study. Synthesis of a new iodine labeled D-glucosamine derivative; development of the iodine-123 labeling method and the obtained glucose derivative biostudy.

Materials and methods. Synthesis of 2-N-(6-iodohexanoyl)-D-glucosamine was carried out through established techniques in organic chemistry. Infrared spectroscopy and nuclear magnetic resonance spectroscopy were used to establish the test compound structure. Isotope change between iodine-127 and iodine-123 of glucosamine derivative was conducted using the heating of mix of the compound and Na123I in acetone. The radio-TLC method was applied to estimate the radiochemical purity of 2-N- (6-iod-123-hexanoyl) -D-glucosamine. The safe application and test of drug pharmacokinetic parameters study was performed on intact Wistar male rats.

Results. An original 2-N-(6-iodohexanoyl)-D-glucosamine synthesis method was proposed. According to the method, an intermediate synthesis succimide-1-yl 6-iodohexanoate was obtained by the cyclohexanone oxidative cleavage reaction. The radiochemical purity of 2-N-(6-iodo-123-hexanoyl)-D-glucosamine was more than 97%.

Conclusion. 2-N-(6-iodohexanoyl)-D-glucosamine was synthesized and iodine-123 labeled. When investigating the proposed radiopharmaceutical safety and pharmacokinetics, it was shown the drug lacks acute toxicity through intravenous injection and is excreted renally by glomerular filtration.

Polyguanidines are characterized by pronounced antimicrobial activity and are widely used as the main active substance of disinfectants. Polymers of this class possess the property of gel formation, which, together with biological activity, opens the prospect of obtaining an effective single-component agent or basis for an external preparation for the therapy of skin lesions. Earlier, we developed a method for the production of a hydrogel based on polyhexamethyleneguanidine hydrochloride, which involves the cross-linking of the terminal amino groups of the branched polymer with formaldehyde.

The purpose of the study was to observe the effect of hydrogel polyhexamethyleneguanidine hydrochloride on the progression of wound healing.

Materials and methods. An experiment on the evaluation of the wound healing action of hydrogel was carried out under conditions simulating a linear cutaneous wound, a muscular wound, and a thermal burn. The comparative drug was the pharmacopoeian drug Levomecol.

Results. It has been established that hydrogel has a pronounced wound healing effect, as evidenced by the results of ruminant thoracic anatomy and pathomorphology of the sections, which shows accelerated ripening of granulation tissue and scar formation. By the method of vulnografiya it was shown that the daily decrease in wound area is most pronounced in the hydrogel group, which also indicates a pronounced reparative effect. It was determined that the hydrogel activates the growth of antioxidatic activity and leukocytes in the blood of animals in dynamics on the 10th, 17th and 24th day of the experiment, amounting to 56, 34 and 21%, and of leukocytes – 32, 30, 10% in relation to the intact animals.

Conclusion. Thus, on the model of a linear cutaneous wound, a muscular wound, and a thermal burn, the healing effect of the hydrogel PGMGh/f is established, as evidenced by the results of the early exercise, vulnografiya and pathomorphological studies. It is noted that the hydrogel PGMG h/f has an effect on the content of antioxidants and leukocytes in the blood, contributing to the normalization of their quantity.

Purpose. Study the topography of cells, expressing villin, p53, Bcl-2, and PUMA in the intestinal mucosa in the non-infectious colitis.

Materials and methods. We studied the morphology and localization of the immunoreactive markers of apoptosis in small intestine and bowel with ulcerative colitis and Crohn’s disease, using the material of 20 autopsies and 40 biopsies.

Results. In the focus of the specific inflammation in the mucosa, we discovered numerous cells, in various degrees expressing anti- and proapoptotic molecules. In the control material, the antiapoptotic factors (villin and Bcl-2) localized mainly in the enterocytes, while the proapoptotic factors (p53 and PUMA) were expressed in the cells of the lamina propria of the mucosa. The reverse correlation between the number of cells expressing p53/PUMA and the villin/Bcl-2 positive cells had been discovered. At the same time proapoptotic molecules were discovered in the enterocytes and in the cells of the lamina propria of intestinal mucosa.

Conclusion. The obtained data points to the important role of apoptosis in pathomorphogenesis of chronic non-infectious intestinal inflammation. The chronization of the process and the nature of the intestinal damage in the UC and CD are connected with balance of the regulative anti- and proapoptotic factors. The cells, expressing those factors, demonstrate the reverse number dependence.

Objective. Estimation of the response time and accuracy of emotional stimuli during the fMRI task fulfillment in participants suffering from mild to moderate depressive disorder or from dysthymic disorder.

Materials and methods. 21 subjects with mild to moderate depressive disorder or dysthymic disorder (D) participated, and 21 healthy volunteers (H) matched by age and sex ratio were included in the control group.  In two fMRI paradigms subjects were observing photos of the faces with different emotional expressions. The first task was to guess the gender of the people on the screen, and the second one was to recognize the emotion experienced by the person in the photo. In the third paradigm participants were sorting different images into pleasant and unpleasant. The subjects responded by pressing one of two buttons. The response time and accuracy were the subjects of analysis.

Results. On the most of the computed parameters patients with depressive disorder did not differ from controls. However, in the first paradigm these subjects demonstrated slower reaction to neutral (H = (1415 ± 408) ms,  D = (1 878 ± 850) ms; t = 2.25; p < 0,05) and disgusted (H = (1 183 ± 310) ms, D = (1 526 ± 646) ms; t = 2.20; p < 0.05) expressions, and greater standard deviations of the response time to disgusted (H = (219 ± 125) ms,  D = (675 ± 645) ms; t = 3.18; p < 0,01), happy (H = (445 ± 310) ms, D = (836 ± 579) ms; t = 2.73;  p < 0.05), surprised (H = (580 ± 438) ms, D = (1 043 ± 785) ms; t = 2.36; p < 0,05), and neutral  (H = (487 ± 416) ms, D = (895 ± 727) ms; t = 2.23; p < 0.05) faces. On the second stage group of participants with depressive disorder had greater standard deviation of the response time to disgusted portraits (H = (1 506 ± 1 273) ms, D = (2 168 ± 1 355) ms; U =131; p < 0.05). Moreover, subjects diagnosed with a depressive disorder less often chose the answer “happy” (H = (6,8 ± 1,1) ms, D = (6.0 ± 0.8) ms; U = 131; p < 0.05) while guessing the emotion in the photo.

Conclusion. Participants diagnosed with mild to moderate depressive disorder or dysthymic disorder perform significantly slower than healthy ones during the “background” processing of the facial expressions and also tend to identify mimic as happy less often than controls while aiming to recognize the feelings of others. However, the role of these features in the progress of depressive disorders and their perspectives as diagnostic markers are subjects for further research.

Currently magnetic resonance imaging (MRI) is one of the key diagnostics methods of various diseases. Utilizing various contrast agents based on magnetic nanoparticles can improve the diagnostic efficiency and, consequently, the quality of the subsequent treatment. The most promising contrast agents are cubic magnetite nanoparticles, due to their high relaxation rates, as well as biocompatibility and biodegradability.

Thereby, the purpose of this work was to evaluate the effectiveness of MRI imaging of tumors by cubic magnetite nanoparticles (CMN).

Materials and methods. For this purpose, the synthesis of 15 nm CMN modified with biocompatible copolymer plurlonic F127 was carried out. Synthesized CMN and their water colloids were characterized by a complex of physicochemical methods of analysis. Then, using MRI a study of the effectiveness of contrasting of various tumor types after intravenous administration of CMN aqueous colloids was made. Three models of mouse tumors were used for a comprehensive assessment of obtained results: breast cancer 4T1, colon cancer CT-26 and melanoma B16. MRI studies were performed prior to the administration of the particles, and also after 15 min, 6 hours and 24 hours after injection in T2-weighted regime in two mutually orthogonal projections.

Results. The analysis of the obtained results showed that the most effective accumulation of particles was found in the 4T1 (100%) and B16 (57%) models, and in the case of CT-26 model the accumulation efficiency was 50% due to the effect of the permeability of blood vessels.

The purpose of the study is an analysis of the consumption of antibacterial drugs in the therapy of salpingoophoritis in hospital settings and evaluation of changes in the real clinical practice of antibiotic therapy after the introduction of the “Order of medical care for the profile “obstetrics and gynecology...”.

Materials and methods. In a retrospective study, an assessment was made of the prescriptions of antibacterial drugs in the therapy of salpingoophritis in specialized treatment and prophylactic institutions of the city of Tomsk in the period 2010–2014. The analysis included 160 case histories. The structure of prescriptions was evaluated on the basis of the application of anatomical-therapeutic-chemical classification and international non-proprietary names (INN), the structural improvement factor K. Gatev was calculated. To quantify the consumption of medications, the calculated daily dose (PDD) was used.

Results. Comparative analysis of antibacterial therapy of salpingoophoritis in hospital before and after the introduction of the “Order of medical care for the profile of «obstetrics and gynecology...”. Leading groups of antibacterial drugs were identified.   А comparative analysis of the frequency of assignment of various INN was made. The К. Gate’s coefficient was 0.281. The calculation of the average prescribed daily doses of antibacterial drugs was performed.

Conclusion. The review of the consumption of antibacterial drugs for salpingoophoritis therapy in hospital settings before and after the introduction of the “Order of medical care for the profile “obstetrics and gynecology...”, showed that the range of antibacterial drugs used increased from 18 to 24 INN, mainly due to the inclusion of modern medicines. In the structure of appointments in 2013–2014, the proportion of drugs not recommended for use by the «Order of medical care for the profile of «obstetrics and gynecology» was 37.5%. It was found that PDD clarithromycin, clindamycin and cefotaxime did not meet the recommended dosing regimens specified in the clinical recommendations for antibiotic therapy. The gap between actual clinical practice and existing clinical recommendations determines the need for in-depth pharmacoepidemiological evaluation to identify the causes and develop measures of an organizational and educational nature to optimize the use of medications.

The aim of the study was to investigate the relationship between food hypersensitivity, inflammation markers and the cytokine profile in children with autism spectrum disorders (ASD).

Materials and methods. The concentration of specific IgG for 111 food antigens was measured via the modified immunological method designed by the ImmunoHealth company. In addition, we performed routine biochemistry tests and immunoassay of interleukins. All children with ASD followed the recommended eliminating diet during 6 months. In order to check their physical and mental condition, their parents completed the autism treatment evaluation checklist (ATEC), both before and after the diet (Bernard Rimland and Stephen M. Edelson of the Autism Research Institute).

In result, we detected the high frequency of hypersensitivity to cereal and dairy products in children with ASD. Moreover, the intensity of hypersensitivity correlated with ATEC score. We also determined that the cytokine profile in children with ASD was different from that in the control group. In particular, the concentration of IFNγ in serum, as well as the IFNγ/IL-10 and IFNγ/IL-4 ratio, were significantly higher in children with ASD. The revealed changes in the cytokine profile correlate with the specific hypersensitivity for cereal and dairy food antigens as well as with ATEC score.

Objective. Mesenchymal stromal cells (MSCs) promote the differentiation of unprimed macrophages (Mр) or classically activated M1 cells towards alternatively activated, M2 macrophages. The aim of the work was to study the ability of MSC to induce M1→M2 switching by comparing the MSC effects on polarized M1 macrophages and monocytes stimulated by granulocyte-macrophage colony-stimulating factor to M1 differentiation.

Material and мethods. MSC were co-cultured with monocytes for 7 days or M1 macrophages for 48 hours in Transwell system to prevent direct cell-to-cell contacts. To characterize generated Mр, classical M2 marker CD206, allostimulatory activity in a mixed lymphocyte culture (MLC), and the ability to secrete pro-/antiinflammatory mediators were analyzed.

Results. Co-cultivation of MSCs and M1 macrophages led to the appearance of phenotypic (increased expression of CD206) and functional (decrease in allostimulatory activity) features of M2 phenotype. When MSCs were cultured with monocytes in the M1-inducing medium, generated Mр elicited a pronounced stimulating activity in MLC similar to that of M1 (stimulation index 3.45 and 3.4, p = 0.46) and significantly higher than allostimulatory activity of M2 cells (3.45 vs 2.2, p = 0.03). In addition, MSCs did not influence the expression of CD206, as well as the production of pro- (IL-1β, TNF-α, IL-6, IL-12) and anti-inflammatory (IL1-ra, IL-4, IL-10) cytokines, immunoregulatory cytokines (IFN-γ, IL-17) and chemokines (IP-10, MCP-1, MIP-1b, Rantes, Eotaxin).

Conclusions: The ability of MSC to induce the M2 phenotype depends on the stage of differentiation of monocyte/macrophages. MSCs promote M1→M2 switching in cultures of polarized M1 macrophages. In contrast, when MSCs interacted with monocytes in M1-inducing medium, a population of M1-like macrophages is formed with high allostimulatory activity and typical for M1 spectrum of produced cytokines and chemokines.

The article presents the background of healthcare system computerization development starting from the time when preconditions for IT systems implementation appeared up to the present moment. It outlines the problems that emerged in the course of implementing the projects aimed at computerizing the RF Healthcare System and providing a high-technology support for it; it features also the indicators related to financial investments into the healthcare information systems. Based on the reports of the authorized agencies the project implementation efficiency is analyzed and solution options for the existing problems are shown. The article reveals development prospects for IT implementation in healthcare.

Objective. Study of IT systems development and incorporation into the practical healthcare structure of the Russian Federation based on the freely available data. Laws and regulations, including reports in healthcare, publications of Russian and foreign lead researchers in economics and medical administration, analytical reviews of consulting companies such as RBC, Price Waterhouse Coopers (London, UK), C-News Analytics (Russia, Moscow), and Vademecum business magazine (Russia, Moscow).

Results. The healthcare computerization process in Russia is slower than it is set out in the Governmental plans. The most common and significant problems include the following: lack of funding for the computerization process in general; irrational distribution of resources within the projects and selection of a costly computerization strategy from the beginning; corrupt practices; conflicts between customers with the contractors because of which many projects were not implemented; management problems; a clash between the current legislation to modern technologies and trends, lack of efforts aimed at implementation of healthcare information systems on the part of the regional authorities.

Conclusion. To make the healthcare computerization more successful it is required to awaken a commercial interest in the private IT companies to attract additional investment. Personal responsibility of the officials in charge of the computerization should become more stringent in case of a delay in a project or a project failure, the government procurement system should be improved in order to attract the most qualified integrators, the interaction between healthcare managers at various levels with the integrators should be facilitated through reducing bureaucratic «paper» load. At the state level it is necessary to focus on the operational improvement of the RF legislation to ensure the progressive development and implementation of information technologies.

In the process of evolution of eukaryotes has formatted a highly organized mechanism for maintaining and regulating intracellular calcium homeostasis, which is one of the most important components of cell signaling in all branches of the phylogenetic tree. Intracellular calcium controls numerous physiological processes in the cell. Ca2+ forms signals as their spatial-temporal distribution. The frequency and amplitude of calcium oscillations depends on the signal strength. Calcium signals causing long-term or short-term responses of cells. Mainly, calcium signals in lymphocytes mediate gene expression program initiation that leads to proliferation, differentiation and production of proinflammatory cytokines also activate formation of inflammasome. Therefore, calcium signals mediate immune, and inflammatory response, autoimmune reaction of lymphocytes. The main mechanism of calcium signaling in lymphocytes is store-dependent Ca2+ current. Mobilization of cellular Ca2+ in response to receptor stimulation commonly occurs through release of Ca2+ ions from intracellular Ca2+ stores or influx across the plasma membrane through calcium - selective channels. Calciumselective channels are assembled from two protein families: the Orai proteins which form the ion channel pore, and the stromal interaction molecule (STIM) proteins which function as endoplasmic reticulum calcium sensors and activators of the channel. Stim protein is a transmembrane monomer which is localized at the membrane of the endoplasmic reticulum. This molecule is a sensor Ca2+ in response to emptying store activates calciumselective channels the plasma membrane. These channels express proteins Orai which are tetramers forming inside the channel pore and act as a site Ca2+. Orai binds to Stim. Orai proteins are activated after receiving information from Stim about Store depletion. Thus, the relationship and coordination of Stim and Orai proteins provides store - dependent Ca2+ current and causes cellular functional responses. Increased Ca2+ levels induce the activation of transcription factors such as NFAT, JNK1, MEF2, CREB, and, in most cases, is a crucial factor in the all differentiation or death. In this review, the mechanism of the store-dependent Ca2+ current in lymphocytes is presented.

The intensive study of the cellular approaches for the correction of different pathologies, including immunopathological processes and oncology, as well as the investigation of the immunosuppressive role of the regulatory T-cells (Tregs) made conditions for the development of techniques of the cell-based correction of immune-mediated states, such as autoimmune pathology or transplantation. Since there are few Tregs in periphery and no specific Treg marker is known, the sorting of the whole blood yields insufficient number of cells. That is why it is emerging to search for optimal conditions of Treg generation and expansion using proliferation stimulators and targeted differentiation of the “pure” Treg population that does not involve the proliferation of effector cells. To date, promising results of the Treg immunotherapy to induce allospecific tolerance in recipients having transplanted organs or tissues were obtained in laboratory experiments and clinical trials. The key problems of this therapy are the lack of knowledge about the mechanism of action and the specific phenotype of the most efficient tolerance-inducing Tregs, and the difficulties to obtain stable populations of functional Tregs. Moreover, it is still unknown how to obtain antigen-specific Treg populations and what the mechanism of their action is. In this review the protocols of Treg generation are summarized and the clinical data on the Treg use for the induction of allo-specific tolerance in transplantation are analyzed.

The purpose of the present literature review is a systematization of known evidence on the problem of postoperative delirium as a frequent complication in elderly and senile patients during extensive reconstructive 

surgery on the spine and large joints. The review, which is based on publications of foreign and native authors, provides insights into current understanding of the pathogenesis, risk factors, diagnosis, methods of treatment, and prevention of these complications. The number of operations in traumatology and orthopedy is increasing. Accordingly with this fact, we are seeing an increase the number of cases of postoperative delirium. We know that the risk of delirium is linked with patient age. The interest to this problem is growing and has clinical and economical background. The etiology of delirium is considered to be multivariate. The development of diagnostic tools is playing a very important role and provides control of delirium in intensive care unit. Common understanding of this state’s pathophysiology and the opportunity to participate another physician leads to correct organization of treatment process. The knowledge of acute postoperative delirium in intensive care unit is being formed. The basic concept of postoperative delirium varies from its definition psychiatry and narcology due to differences in how different specialties treat the disorder. The risk factors of treatment are estimated. The controlled sedation is a clear trend. The experience of practical application dexmedetomidin for prevention and treatment of postoperative delirium is accumulated. Although the value of drug- therapy is difficult to overestimate the great influence on the result have non- pharmalogical methods.

The main trends and prospects of development of nuclear medicine, problems and possible ways of their solution are considered in the article. The main scientific directions in the development of radiopharmaceuticals for the diagnosis and radionuclide therapy of malignant tumors (radiopharmaceuticals that can accumulate in tissues surrounding the tumor; radiopharmaceuticals that can accumulate on the membranes of tumor cells, radiopharmaceuticals that can accumulate in tumor cells, radiopharmaceuticals for sentinel lymph nodes detection). It is shown that the current trends in the development of nuclear medicine are closely related to theranostics (therapy + diagnostics) using radiopharmaceuticals obtained on the basis of a target compound labeled with different isotopes intended for diagnosis or therapy. In nuclear medicine, such tandems are used to individualize and plan of radionuclide therapy. The results of our own research on the development of radiopharmaceuticals for tumor imaging and detection of sentinel lymph nodes are presented. The functional utility of radiopharmaceuticals and the prospects of their clinical use are shown.

In this manuscript, a unique case of HPV16-positive breast cancer is examined. The presence of HPV infection in the tumor is confirmed by two independent methods (PCR and immunohistochemistry). It is shown that in the presence of adverse factors of prognosis (lymphogenous metastasis, high level of Ki67 expression, presence of chromotrypsis in the tumor, and high level of genetic instability), a patient with a HPV-positive breast tumor has more than 8-year disease-free survival.

Having taken into consideration still remaining high rate of cerebral stroke in the Republic of Kazakhstan Ministry of Health developed the State anti-stroke programme for the period of 2016–2020 years. The regional brain stroke centre with 30 beds per 250.000 people has been working at the premises of The Hospital of Emergency Medical Service (HEMS) since July 2012. Main results of Aktobe stroke centre work are submitted in this article. There are some databases of the brain stroke innovative methods of treatment use, such as thrombolytic therapy, surgical and endovascular methods of treatment.

A study of a child with intellectual disability revealed an enlarged p-arm in chromosome 13 and amplified rDNA. qRT-PCR showed an approximately 6-fold increased level of rRNA in the patient’s blood samples. fMRI study revealed changes in uncinate fasciculus. His father is a carrier of the same chromosome, healthy and has a normal level of rRNA.