[The effect of the use of the drug recognan (citicoline) on the state of higher mental functions in patients with mild cognitive impairment]. / Vliyanie preparata Rekognan na sostoyanie vysshikh psikhicheskikh funktsii u patsientov s legkimi kognitivnymi narusheniyami.

OBJECTIVE: The aim of the observational program was to study the effect of the use of the drug recognan (citicoline) on the state of higher mental functions (memory, attention, visual-motor coordination, dynamic praxis,verbal thinking and imagination) in patients with mild cognitive impairment. MATERIAL AND METHODS: A survey of 54 subjects (16 of them male and 38 female) aged 18-50 years (average age 28.5±10.5 years) was conducted with a diagnosis of «Mild cognitive impairment¼ («F06.7¼). The group was randomized into 2 subgroups: the main subgroup (26 people) received oral therapy with the drug Recognan, for 30 days, with the daily dosage of the drug being 500 mg. In the control group (28 people), nootropic drug therapy was not performed. Standard psychometric techniques were used to study higher mental functions. All subjects were examined three times (initially, in the middle of the study - on day 15, at the end of the study - on day 30). RESULTS AND CONCLUSION: After 2 weeks of treatment with recognan, there was an improvement in concentration in 81.9%, memory in 50% (p=0.008), verbal imagination productivity in 68.2% (p=0.015), counting functions in 60% (p=0.015), visual-motor coordination and dynamic praxis - in 86.4% (p=0.003), increased speed and efficiency of mental work (p=0.001). After a 30-day course of treatment with recognan, there was an improvement in memory in 58.3% of patients (p=0.007), an increase in concentration in 64%, an improvement in counting functions in 64.3% (p=0.011), verbal imagination productivity in 63.3%, visual-motor coordination and dynamic praxis in 86.4% (p=0.007), speed and efficiency of mental work (p=0.006), which indicates a complex positive effect of recognan on higher mental functions in patients with mild cognitive impairment cognitive impairment.

[The influence of the drug recognan (citicoline) on neurodynamic characteristics of mental activity in patients with mild cognitive impairment]. / Vliyanie preparata Rekognan (tsitikolin) na neirodinamicheskie kharakteristiki psikhicheskoi deyatel'nosti u patsientov s legkimi kognitivnymi narusheniyami.

OBJECTIVE: The aim of the study was to study the effect of the drug recognan (citicoline) on the neurodynamic characteristics of mental activity in patients with mild cognitive impairment. MATERIAL AND METHODS: A survey of 58 subjects (17 of them male and 41 female) aged 18-45 years (average age 27.2±12.5 years) was conducted. Clinical diagnosis according to ICD-10 «Mild cognitive impairment¼ (F06.7). The main subgroup included29 people received oral recognan therapy (in solution, 100 mg in 1 ml) for 30 days, with a daily dosage of 500 mg (5 ml of solution). In the control group (29 people) drug therapy was not performed. Tests were used: «Graphic sample¼, the sample on the reciprocal coordination of the hands (Ozeretsky test), test for the compression of fingers, the test «number series¼. The follow-up period was 30 days. All subjects were examined three times (initially, in the middle of the study - on day 15, at the end of the study - on day 30). RESULTS AND CONCLUSION: The results obtained showed that the use of the drug recognan (citicoline) has a positive effect on the indicators of visual-motor coordination and spatial representations, neurodynamic characteristics of movement, and cognitive functions. After a 2-week treatment with recognan improved graphical sample, 84% of patients, with reliable improvement according to the Wilcoxon (p=0.0002), the sample in the compression of the fingers 60%, as well as coordination 60%, the accounting functions in 44%. After a month (30 day) treatment course recomanem there was an increase in indices of samples for the compression of fingers in 71.4% of patients, with significant improvement (p=0.0499) and run the graphical samples of 71.4%, coordination at 46.4%, counting functions - 48% patients.

[Features of positive personality phenomena in patients with mild cognitive impairment and asthenic syndrome treated with recognan (citicoline)]. / Vliianie primeneniia preparata Rekognan (tsitikolin) na proiavleniia pozitivnykh lichnostnykh kachestv u patsientov s astenicheskim sindromom i legkimi kognitivnymi narusheniiami.

AIM: To assess the formation of positive personality phenomena in patients with mild cognitive impairment and asthenic syndrome during the treatment with recognan (citicoline). MATERIAL AND METHODS: Thirty-eight patients (17 men and 21 women), aged 18 to 45 years (mean age 27.8±12.1 years), with asthenic syndrome with mild cognitive impairment (ICD-10 F06.7) were examined. Patients were divided into two groups: 20 people in the main group and 18 people in the comparison group. The main group received recognan (orally, in solution, 100 mg in 1 ml) for 30 days, the daily dosage of the drug was 0.5 g (5 ml solution). The comparison group did not receive any medications. Adapted methods of positive personality psychology were used: the Fordyce Emotions Questionnaire, the Subjective Happiness Scale (SHS), the Adult Hope Scale (AHS), the Satisfaction with Life Scale (SWLS), M. Atkinson's Scale of Emotional Maturity, the projective technique 'Map of experiences'. The follow-up period was 30 days. All subjects were examined three times (at baseline, 15 and 30 days after treatment). RESULTS AND CONCLUSION: After a month of treatment with recognan, there was an improvement of positive personality traits and a significant decrease in negative experiences, indicating the positive impact of the drug on the formation of positive personality manifestations and compensation for emotional disorders in patients with mild cognitive impairment and asthenic syndrome.

Positive Personal Qualities and Depression

The article describes the results of studying the relationship between positive personal qualities and depression, as an antagonist of positive parameters. The following positive characteristies were studied: subjective well-being, happiness, hope, subjective success of activity, the ability to determine life goals, emotional maturity, the ability to comprehend the present, satisfaction with life, desire and initiative for personal growth, inclination to curiosity and research, motivation to seek satisfaction with marriage. The level of depression was also measured. Positive characteristics and contrasted depression show correlations among themselves, which indicates a general factor of positivity. A positive person is positive in all spheres of life and at the same time does not show any depressive manifestations. In general, depressivity is antagonistic to a person's positivity (AU)

[Current treatment options for autonomic, cognitive and emotional disorders in patients with asthenic syndrome treated with recognan (citicoline)]. / Vozmozhnosti lecheniia vegetativnykh, kognitivnykh i émotsional'nykh rasstroistv u patsientov s astenicheskim sindromom pri ispol'zovanii Rekognan (Tsitikolin).

AIM: To study the efficacy of recognan (citicoline) in the treatment of cognitive, emotional, autonomic, asthenic disorders in patients with asthenic syndrome. MATERIAL AND METHODS: Thirty-eight subjects (17 men and 41 women), mean age 27.75±12.05 years, with asthenic syndrome (ICD-10 F48.0 - Neurasthenia) were studied. The sample was randomized into 2 subgroups: the main group (n=20) received oral therapy with recognan (100 mg in 1 ml) for 30 days, while the daily dosage was 500 mg (5 ml). In the control group (n=18), no drug therapy was performed. Patient's state was assessed with a large battery of psychological tests and psychometric scales. The follow-up period was 30 days. All participants were examined three times (initially, in the middle of the study (day 15), in the end of the study (day 30)). RESULTS AND CONCLUSION: Asthenic syndrome was detected in 100% of the patients (total asthenia was noted in 70%, decreased activity in 70%, decreased motivation in 40%, physical asthenia in 45%, mental asthenia in 50%). Recognan (citicoline), used for 2 weeks or one month, has a positive effect on the compensation of autonomic, asthenic cognitive and emotional disorders and increases stress resilience of the patients.

[Cognitive and emotional disorders in university students and teachers: the possibility of treatment with recognan (citicoline)]. / Kognitivnye i psikhoémotsional'nye narusheniia u uchashchikhsia i prepodavatelei vuzov: vozmozhnosti korrektsii s pomoshch'iu preparata rekognan (tsitikolin).

AIM: To study the efficacy of recognan (citicoline) in treatment of cognitive, emotional, autonomic, asthenic disorders in university students and teachers. MATERIAL AND METHODS: Fifty-eight subjects (17 men and 41 women), mean age 27.75±12.05 years, including who 42 students and 16 teachers were studied. The sample was randomized into 2 groups (29 each): the main sub-group received oral therapy with recognan for 30 days, while the daily dosage was 500 mg (5 ml). In the control group, no drug therapy was performed. Patient's state was assessed with a large battery of psychological tests and psychometric scales. The follow-up period was 30 days. All participants were examined three times (initially, in the middle of the study (day 15), in the end of the study (day 30)). RESULTS AND CONCLUSION: Asthenic state was detected in 69%, autonomic dysfunction in 82.7%, sleep disorders in 75.8% of subjects. A high level of state anxiety was revealed in 22.2%, trait anxiety in 29.8%, a high level of stress was determined in 6,9%. It is shown that the use of recognan (citicoline) has a positive effect on compensation of autonomic and asthenic disorders, improves cognitive status, corrects psycho-emotional disorders, when used as a short (2 week) and month course.

Modern Approaches for Identification of Modified Nucleotides in RNA.

This review considers approaches for detection of modified monomers in the RNA structure of living organisms. Recently, some data on dynamic alterations in the pool of modifications of the key RNA species that depend on external factors affecting the cells and physiological conditions of the whole organism have been accumulated. The recent studies have presented experimental data on relationship between the mechanisms of formation of modified/minor nucleotides of RNA in mammalian cells and the development of various pathologies. The development of novel methods for detection of chemical modifications of RNA nucleotides in the cells of living organisms and accumulation of knowledge on the contribution of modified monomers to metabolism and functioning of individual RNA species establish the basis for creation of novel diagnostic and therapeutic approaches. This review includes a short description of routine methods for determination of modified nucleotides in RNA and considers in detail modern approaches that enable not only detection but also quantitative assessment of the modification level of various nucleotides in individual RNA species.

[Immunogenicity of recombinant analog of antitumor protein lactaptin].

Therapeutic monoclonal antibodies and recombinant proteins including cytokines are commonly used in the treatment of cancer and inflammatory diseases. In most cases, these protein-based drugs exhibit a high therapeutic efficacy, which is unfortunately frequently associated with a variety of side effects. We have investigated the in vitro and in vivo immunogenicity of recombinant antitumor protein lactaptin (RL2). Based on the qRT-PCR analysis, we have shown that, in MDA-MB-231 human breast adenocarcinoma cells, RL2 suppresses the NF-kB signaling cascade that regulates the reactions of innate immunity. RL2 inhibits the expression of the CXCL1 protein and apoptosis inhibitor A20 and enhances expression of IkB, NF-kB repressor. The ELISA method has been used to evaluate the antibody titer in the blood of mice, which received single and triple intravenous or intraperitoneal injections of RL2. The multiplex immunoassay of 23 cytokines in the mice blood has shown that the RL2 injections lead to a slight increase in the levels of systemic pro-inflammatory cytokine interleukin-5 (IL-5) and keratinocyte chemoattractant (KC), a homologue of human macrophage inflammatory protein-1 (MIP-1). These observations indicate the low immunogenicity of the recombinant lactaptin analog, which can be considered to be a potential molecular drug candidate for further clinical development.

[Laparoscopic transperitoneal adrenalectomy].

AIM: To analyze the results of laparoscopic adrenalectomy (LAE) in patients with adrenal gland tumors. MATERIALS AND METHODS: From 2011 to 2016, 24 patients (15 men, 9 women), mean age 49.6 +/- 8.2 years, underwent LAE. The right, left and bilateral LAE was performed in 12, 10 and 2 patients, respectively. Indications for surgery were mainly primary and metastatic adrenal tumors. The operations were performed using a transperitoneal 4-port approach. RESULTS: Twenty six LAE were successfully performed in 24 patients. There were no conversions. Blood transfusion was used only in 1 patient, who had a history of the laparoscopic left nephrectomy for the renal cell carcinoma 2 years earlier. She had bleeding due to a spleen injury during the left LAE. She also developed acute postoperative pancreatitis, resolved by conservative therapy. The mean intra- and postoperative blood loss was 160 (120-750) ml, the operative time was 135 (100-205) min, and the length of hospital stay was 4 (3-5) days. Histological examination revealed adenocarcinoma and adenoma in 20 (73.1%) and 6 (26.9%) removed adrenal glands, respectively. CONCLUSION: Laparoscopic adrenalectomy is an effective and safe surgical modality to treat patients with adrenal tumors.

Modified Method of rRNA Structure Analysis Reveals Novel Characteristics of Box C/D RNA Analogues.

Ribosomal RNA (rRNA) maturation is a complex process that involves chemical modifications of the bases or sugar residues of specific nucleotides. One of the most abundant types of rRNA modifications, ribose 2'-O-methylation, is guided by ribonucleoprotein complexes containing small nucleolar box C/D RNAs. Since the majority of 2'-O-methylated nucleotides are located in the most conserved regions of rRNA that comprise functionally important centers of the ribosome, an alteration in a 2'-O-methylation profile can affect ribosome assembly and function. One of the key approaches for localization of 2'-O-methylated nucleotides in long RNAs is a method based on the termination of reverse transcription. The current study presents an adaptation of this method for the use of fluorescently labeled primers and analysis of termination products by capillary gel electrophoresis on an automated genetic analyzer. The developed approach allowed us to analyze the influence of the synthetic analogues of box C/D RNAs on post-transcriptional modifications of human 28S rRNA in MCF-7 cells. It has been established that the transfection of MCF-7 cells with a box C/D RNA analogue leads to an enhanced modification level of certain native sites of 2'-O-methylation in the target rRNA. The observed effect of synthetic RNAs on the 2'-O-methylation of rRNA in human cells demonstrates a path towards targeted regulation of rRNA post-transcriptional maturation. The described approach can be applied in the development of novel diagnostic methods for detecting diseases in humans.

[The influence of recombinant nucleophosmin 1 on artificial RNA internalization into human adenocarcinoma MCF-7 cells].

In this study we obtained and characterized the recombinant analogue of multifunctional nucleolar phosphoprotein nucleophosmin 1 (NPM1) involved in crucial cellular processes such as transcription, reparation and mitosis. The influence ofnucleophosmin 1 on extrcellular RNAs accumulation in human adenocarcinoma cells MCF-7 was analyzed. It was found that incubation of AluY RNA (n > 300 nt), U24 snoRNA analogues (n ~ 80 nt) with Npm1-His6 resulted in RNA-protein non-covalent complexes formation, but not in case of the short oligoribonucleotide (n = 22 nt). It was shown that interaction of AluY RNA analogue with Npm1-His6 significantly increases transfection efficacy of the RNA into MCF-7 human cells. Altogether, these data allow us to conclude, that nucleophosmin 1 not only binds RNA with complex secondary structure, but also promotes uptake and internalization of such RNA by human cells.

[Renal revascularization and long-term cardiovascular survival of patients with atherosclerotic renovascular disease].

The prospective investigation of 185 patients (118 men and 67 women in the age of 35-79 years (on the average 60+/-9 years) with atherosclerotic renovascular disease was carried out. The disease was detected by one- (62%) and two- (38%) hemodynamic value (>50%) of renal artery stenosis. Renal function, arterial pressure, cardiovascular death cases were estimated in 4 groups of patients during the period of 2,5-126 months (on the average 33 months). The patients of the first group (n=103) were undergone the renal revascularization (51 open and 80 endovascular). The patients of the second group (n=20) were after combined open renal revascularization (25) and after performed reconstruction of abdominal aorta and its branches and lower extremities arteries concerning aneurysmatic and occlusive lesions. The patients of the third group (n=19) had only reconstruction of lower extremities arteries concerning their ischemia without renal revascularization. The patients of the fourth group (n=43) haven't been operated because of the refusal of intervention. The lowest rate of survival was in the fourth group, who used the conservative therapy. Long-term survival didn't differ after open and endovascular therapy. The Koks regression analysis showed, that the improvement of long-term survival of the patients was associated with renal revascularization [Exp(B)=0,25, p<0,001] and didn't depend on the method of renal arteries reconstruction. A strategy of careful selection of patients with the application of interdisciplinary approach should be the base of clinical practice in renovascular disease.

Alu- and 7SL RNA Analogues Suppress MCF-7 Cell Viability through Modulating the Transcription of Endoplasmic Reticulum Stress Response Genes.

11% of the human genome is composed of Alu-retrotransposons, whose transcription by RNA polymerase III (Pol III) leads to the accumulation of several hundreds to thousands of Alu-RNA copies in the cytoplasm. Expression of Alu-RNA Pol III is significantly increased at various levels of stress, and the increase in the Alu-RNA level is accompanied by a suppression of proliferation, a decrease in viability, and induction of apoptotic processes in human cells. However, the question about the biological functions of Pol III Alu-transcripts, as well as their mechanism of action, remains open. In this work, analogues of Alu-RNA and its evolutionary ancestor, 7SL RNA, were synthesized. Transfection of human breast adenocarcinoma MCF-7 cells with the Alu-RNA and 7SL RNA analogues is accompanied by a decrease in viability and by induction of proapoptotic changes in these cells. The analysis of the combined action of these analogues and actinomycin D or tamoxifen revealed that the decreased viability of MCF-7 cells transfected with Alu-RNA and 7SL RNA was due to the modulation of transcription. A whole transcriptome analysis of gene expression revealed that increased gene expression of the transcription regulator NUPR1 (p8), as well as the transcription factor DDIT3 (CHOP), occurs under the action of both the Alu- and 7SL RNA analogues on MCF-7 cells. It has been concluded that induction of proapoptotic changes in human cells under the influence of the Alu-RNA and 7SL RNA analogues is related to the transcriptional activation of the genes of cellular stress factors, including the endoplasmic reticulum stress response factors.

[Results of combined reconstructions of the renal arteries, abdominal aorta and its other branches in patients with atherosclerosis].

A comparative analysis was made of clinical indices and long-term survival in 20 patients (13 men and 7 women of mean age 62 +/- 2 years), having multifocal atherosclerosis of the renal arteries (RA), abdominal aorta and arteries of lower extremities (LE) (11 aneurysms, 7 occlusive lesions of the aorta and 3 of its unpaired branches) who underwent combined reconstructions, with patients having similar lesions, but not operated (12) or operated only on RA or on the arteries of LE (45). The groups of patients had no great differences except more pronounced renal dysfunction (RD) in the first of them. In spite of high postoperative lethality (20%) mainly due to acute renal failure (3), long-term survival proved to be significantly higher (14 from 16), than in not operated (3 from 12) (p = 0.00001) and had better tendency than in those operated on the same basin (35 from 45). In addition, the patients after combined operations had substantially decreased systolic and diastolic arterial pressure (159 +/- 13 vs. 132 +/- 9, p = 0.00001; 91 +/- 5 vs. 83 +/- 7, p = 0.010) and also stabilized renal function.

[The analysis of biochemical markers of MCF-7 cells apoptosis induced by recombinant analog of lactaptin].

Earlier we isolated and characterized human milk pro-apoptotic peptide - lactaptin and generated its engineered analog - RL2. It was shown that both lactaptin and RL2 are capable to induce apoptotic death of MCF-7 cells. In this report we have analyzed biochemical markers of RL2 induced MCF-7 apoptosis. The activation of initiator and effector caspases as well as mitochondrial membrane potential and cytoplasm membrane changes were analyzed using flow cytometry and Western-blot methods. We have found that RL2 induced apoptotic death of MCF-7 cells was accompanied by PS exposure on the plasma membrane surface. It also was shown that RL2 has induced dissipation of mitochondrial membrane potential and resulted in activation of initiator caspases 8, 9 and effector caspase 7.

Analogues of Artificial Human Box C/D Small Nucleolar RNA As Regulators of Alternative Splicing of a pre-mRNA Target.

Small nucleolar RNAs (snoRNAs) play a key role in ribosomal RNA (rRNA) biogenesis. Box C/D snoRNAs guide the site-specific 2'-O-ribose methylation of nucleotides in rRNAs and small nuclear RNAs (snRNAs). A number of box C/D snoRNAs and their fragments have recently been reported to regulate post-transcriptional modifications and the alternative splicing of pre-mRNA. Artificial analogues of U24 snoRNAs directed to nucleotides in 28S and 18S rRNAs, as well as pre-mRNAs and mature mRNAs of human heat shock cognate protein (hsc70), were designed and synthesized in this study. It was found that after the transfection of MCF-7 human cells with artificial box C/D RNAs in complex with lipofectamine, snoRNA analogues penetrated into cells and accumulated in the cytoplasm and nucleus. It was demonstrated that the transfection of cultured human cells with artificial box C/D snoRNA targeted to pre-mRNAs induce partial splicing impairments. It was found that transfection with artificial snoRNAs directed to 18S and 28S rRNA nucleotides, significant for ribosome functioning, induce a decrease in MCF-7 cell viability.

[Surgical treatment of fibromuscular dysplasia of renal arteries in adults].

The authors have analyzed an experience with treatment of 16 patients. All the patients had renovascular hypertension (RVH) and 3 of them had renal dysfunction. Revascularization of the kidneys (RK) was fulfilled in 11 patients by shunting (9) or prosthesis (2) of the renal arteries. In 7 patients percutaneous endovascular angioplasty (PEA) was used. There were neither complications nor lethal outcomes. Arterial pressure normalized in 7 patients and in 9 RVH was better. In the long-term period (at the average within 21 months) 14 patients were followed-up. In 3 patients having perimedial and intimal fibroplasty of RA after PEA restenoses were diagnosed. They had repeated RK. Renal function became better in 1 patient, in 2 patients there was no substantial dynamics. All shunts were passable. The analysis of the data has shown that liquidation of RVH in patients with FMD of RA has inverse dependence on its duration, and decision on the method of RK depends on the type of RA, experience of the specialists, the patients desire included.