[Indicators of cognitive impairment of varying severity in the acute period of ischemic stroke]. / Indikatory kognitivnykh narushenii razlichnoi stepeni tyazhesti v ostrom periode ishemicheskogo insul'ta.

OBJECTIVE: To assess phenotype and identify biomarkers of cognitive impairment (CI) of varying severity in patients in the acute period of ischemic stroke (IS) based on the analysis of clinical and paraclinical indicators. MATERIAL AND METHODS: Two hundred and forty patients with diagnosed IS and presence of CI were examined. Depending on the scores on the Montreal Cognitive Assessment Scale, patients were divided into two groups: group 1 (n=182) with mild CI, group 2 (n=58) with dementia. On admission, stroke severity according to the National Institutes of Health Stroke Scale (NIHSS), activities of daily living assessed by the Barthel Scale and patient independence assessed by the modified Rankin Scale (mRS) were determined. Neuropsychological examination was performed on day 14 and included investigation of episodic memory, executive functions, speech, gnosis, praxis, and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) parameters. Immunological diagnostics included a study of the concentration of cytokines of various groups (interleukin (IL)-1b, IL-6, IL-16, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokines CXCL10, CXCL11, CXCL9, tumor necrosis factor α (TNFα)). Neuroimaging parameters were assessed using brain MRI data with verification of the STRIVE criteria and the medial temporal lobe atrophy scale (MTA). The standard application software package SPSS Statistics, Pandas and SciPy libraries were used for statistical analysis. RESULTS: Patients of group 2 had lower scores in all cognitive domains with the greatest reduction in perception, constructive praxis, semantic information processing and mnestic function. These analyses revealed a higher degree of IQCODE, prevalence of features corresponding to STRIVE/MTA criteria in patients of group 2, while patients of group 1 had higher NIHSS and mRS scores. When serum concentrations of cytokines were assessed, patients of group 1 showed higher concentrations of IL-1b, IL-6, GM-CSF and TNFα, while group 2 patients had higher concentrations of cytokine CXCL10. CONCLUSION: The presence of pre-stroke CI, baseline indicators of the patient's functional status, neuroimaging parameters of MTA/STRIVE and age are reflected in the structure and severity of cognitive deficit in the acute period of IS. Investigation of the role of interleukins, GM-CSF, TNFα and CXCL10 in the pathogenesis of IS and their association with the progression of post-stroke CI requires further studies with a larger sample size and longer follow-up period.

[Bioregulatory drug Newrexan in the treatment of anxiety and dissomnia. Resolution of the Council of Experts (June 8, 2023)]. / Bioregulyatsionnyi preparat N'yureksan v lechenii trevozhnosti i dissomnii. Rezolyutsiya Soveta ekspertov (8 iyunya 2023 g.).

Bioregulatory drug Newrexan in the treatment of anxiety and dissomnia. Resolution of the Council of Experts.

[Treatment of sleep disturbances associated with chronic non-specific low back pain: results of prospective randomized multicenter open-label clinical trial]. / Lechenie narushenii sna, svyazannykh s ostrym nespetsificheskim bolevym sindromom v poyasnichno-kresttsovom otdele spiny: rezul'taty prospektivnogo mnogotsentrovogo randomizirovannogo otkrytogo sravnitel'nogo v parallel'nykh gruppakh klinicheskogo issledovaniya.

OBJECTIVE: A comparative study of the effectiveness and safety of novel combination naproxen sodium and diphenhydramine in subjects with low back pain along with transient insomnia. MATERIAL AND METHODS: It was an open label, randomized, comparative, parallel group and multi-center clinical study. Subjects were randomised into one of three treatment arms: naproxen sodium 440 mg/diphenhydramine 50 mg, naproxen sodium 550 mg, Paracetamol 1000 mg/diphenhydramine 50 mg. All the subjects were advised to apply study drug ones before sleep for 3 days. All subjects also received naproxen sodium 275 mg as background therapy. The primary end-point was wake time after sleep onset (WASO) measured by actigraphy. Other secondary sleep and pain end-points were also assessed. RESULTS: Efficacy analysis was performed for intent-to-treat population (n=235 subjects). naproxen sodium 440 mg/diphenhydramine 50 mg combination showed significant improvements in WASO vs. naproxen sodium 550 mg (-42 min p=0.0174), while differences vs. Paracetamol 1000 mg/diphenhydramine 50 mg (-30 min, p=0.0891) were not significant. According to the average pain intensity difference in the lumbosacral spine combination product naproxen sodium 440 mg/diphenhydramine 50 mg was significantly improved compared with naproxen sodium 550 mg (-9.42, p<0.001) and Paracetamol 1000 mg/diphenhydramine 50 (-7.15, p<0.05). CONCLUSION: Naproxen sodium 440 mg/diphenhydramine 50 mg combination demonstrated improvement in sleep maintenance (WASO) vs. naproxen sodium 550 mg and higher efficiency in average daily pain reduction compared with the comparison groups. The treatment was well tolerated There were no serious or unexpected adverse events reported in the study.

[Study of the clinical efficacy and safety of the scheme of step therapy of nonsteroidal anti-inflammatory drugs and a complex of B vitamins in patients with low back pain]. / Issledovanie effektivnosti i bezopasnosti stupenchatoi terapii nesteroidnymi protivovospalitel'nymi preparatami i vitaminami gruppy B u patsientov s ostroi dorsalgiei.

OBJECTIVE: The purpose of the study. Comparison of efficacy and safety of treatment with Texared/Neurobion and Amelotex/Milgama in patients with acute dorsalgia. MATERIAL AND METHODS: An open, observational, retrospective - prospective study involved 70 patients with acute lumbar dorsalgia. Two groups of 35 patients were formed, who were prescribed step therapy with Texared and Neurobion (group 1) and Amelotex and Milgamma (group 2). The groups of patients are comparable by gender (in group 1 - 25 (71%) women, in group 2 - 24 (69%), the average age is 50.1±10.5 and 52.8±12.0 years, respectively. The groups are comparable in the nature and severity of clinical symptoms, but not homogeneous in the nature of concomitant diseases. RESULTS AND CONCLUSION: In two groups, there was a comparable improvement in the condition after treatment according to the Oswestry and Roland-Morris questionnaires, an increase in the quality of sleep by the 10th day of observation. In the 1st group, the decrease in pain syndrome by VAS is more pronounced: by the 3rd visit, the decrease is 7.5 points more than in the 2nd group (p<0.05). In group 1, by the 2nd visit, the median pain intensity for VAS decreased by 10 points (p<0.05), by the 3rd - by 30 points (p<0.05). In group 1, the improvement in general well-being according to the assessment of the patient and the doctor was more pronounced (p<0.05). Evaluation of the effectiveness of both types of therapy demonstrated comparable results, both in the opinion of the doctor and in the opinion of the patient. The results of treatment in both groups are comparable in terms of satisfaction with treatment and ease of use according to the patient's assessment. In group 1, there was less pain of intramuscular administration of the drug. 32 (91%) patients of group 1 positively assessed the convenience of using the proposed treatment regimen. No significant adverse events were detected in the two groups.

[The evaluation of the efficacy of Alflutop in the complex treatment of patients with chronic lower back pain (the observational study ZEITNOT)]. / Otsenka terapevticheskoi effektivnosti Alflutopa v kompleksnom lechenii patsientov s khronicheskoi bol'yu v nizhnei chasti spiny (nablyudatel'noe issledovanie TsEITNOT).

OBJECTIVE: To analyze the effect of Alflutop on neuroinflammation in patients with chronic lower back pain (CBP). MATERIAL AND METHODS: Forty-one patients with a verified CBP diagnosis were enrolled in the study. Alflutop was used for treating CBP, 1 ml once/day, for 20 days. Treatment efficacy was monitored using the Visual Analogue Scale (VAS), DN4 test; the Roland-Morris questionnaire; the index of pain activity in the lumbar spine; and the level of tumor necrosis factor-α (TNF-α) in blood plasma. There were three visits in total: screening (visit 0), treatment start (visit 1, 0-3 days after screening) and visit 2 (3 months later (±7 days) from the start of treatment). RESULTS: Before the start of therapy, in some patients (group 1, n=14 (34.1%) the TNF-α concentration in the blood plasma was below the detectable level (less than 4.0 pg/ml), while in group 2 (n=27 (659%)), the expression of TNF-α in peripheral blood was observed at the level of 6.3 [4.9; 7.4] pg/ml. Patients in group 2 significantly (p<0.05) differed from patients in group 1 by the greater number of CBP exacerbations over the last year as well as by the results of testing on DN4 (higher values) and SBI (greater discomfort). In group 2, a significant relationship was found between the TNF-α level in blood plasma and the number of exacerbations as well as between the TNF-α level and the number of DN4 points. At visit 2, patients in group 2 had a significant (p<0.05) decrease in pain intensity according to VAS, an improvement in the quality of life according to the Roland-Morris questionnaire, a decrease in the severity of the neuropathic component of pain according to DN4 test as well as subjective condition improvement associated with the activity of pain in the lumbar spine. A significant relationship was found between the level of TNF-α and the number of DN4 points after treatment and the period of active observation. CONCLUSIONS: In the majority of CBP patients, the high relapse rate and neuropathic nature of pain may be associated with persistent neuroinflammation due to TNF-α synthesis. Alflutop inhibits the TNF-α expression substantially, which significantly correlates with a decrease in the neuropathic pain syndrome component according to the DN4 questionnaire. The use of Alflutop can be considered as an effective method of treating patients with CBP, which has an impact on the process of neuroinflammation as one of the leading causes of changes in the pain nature and its chronicity.

[Cognitive dysfunction and content of inflammatory markers in patients after coronary artery bypass graft]. / Kognitivnaia disfunktsiia i soderzhanie v krovi markerov vospalitel'nogo otveta u patsientov, perenesshikh aortokoronarnoe shuntirovanie.

AIM: To study the relationship between the content of inflammatory biomarkers and cognitive function in patients after coronary artery bypass graft (CABG) performed in condition of artificial blood circulation (ABC) or open-heart surgery (OHS). MATERIAL AND METHODS: Twenty-nine patients with ischemic heart disease who survived CABG, mean age 62.4±6.2 years, were studied. The ABC group (n=18) and OHS group (n=11) were matched for age and sex. Patients underwent standard clinical examination as well as neurological examination and neuropsychological testing. Concentrations of pro- and anti-inflammatory cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IL-1RA, IFN-γ, IP-10; MCP-1, MIP-1α, MIP-1ß, RANTES, TNF) were determined in blood plasma obtained 24 h before and 2h after surgery using multiplex immunofluorescence assay. RESULTS: In both groups, an increase in concentrations of IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, MIP-1ß and RANTES was observed at point T1. Concentration of IL-1RA was significantly higher only in the ABC group but not in the OHS group. After CABG, an increase in concentrations of IL-8, IP-10, MIP-1ß, IL-1RA was significantly higher in the ABC group. The Montreal scale was the most sensitive test for assessment of cognitive functions in post CABG patients. A significant decrease in scores (>3) was noted in 8 out of 18 patients in the ABC group and in one patient of the OHS group. The correlations between the decrease in cognitive functioning in the 7th day after surgery and plasma cytokine concentration 2 h after surgery were identified for IL-6 (r=0.472; p=0.01); IL-8 (r=0.403; p=0.03); IP-10 (r=0.372; p=0.047); MCP-1 (r=0.470; p=0.01). CONCLUSION: CABG is accompanied by the systemic inflammatory reaction, with the more marked inflammatory effect in patients operated under condition of extracorporeal circulation. CABG with ABC causes an impairment of cognitive functions during the first week in many patients. Impaired cognitive status was associated with the increase in concentrations of proinflammatory cytokines in blood plasma.

[Assessment of changes in the lesions sizes and the incidence of complete epithelialization during the treatment of diabetic foot syndrome over a period of 4 weeks (multicenter study)]. / Otsenka dinamiki ploshchadi rany i chastoty sluchaev polnoi epitelizatsii pri lechenii sindroma diabeticheskoi stopy (rezul'taty mnogotsentrovogo issledovaniya).

AIM: To assess the effectiveness of the collagen biomaterial in treatment process in patients with DFS. MATERIAL AND METHODS: 71 patients 30-80 y.o. with diabetic foot syndrome of varying severity were included in prospective multicenter study. Patients were randomized into two homogeneous groups: control group (n=35) - standard therapy, other 36 patients (main group) were additionally treated with medical device (MD) Collost in accordance with the instructions for use. RESULTS: Biomaterial Collost using in complex treatment of diabetic foot syndrome resulted in more rapid and effective healing of the ulcer. The treatment success increased from 43% to 72%. Complete epithelialization was achieved by 2.6 times more rapidly in conjunction with reduction the incidence of unsuccessful treatment results by 4.1 times.

[Neurological complications in patients with diabetes mellitus type 1 treated with different methods of insulinotherapy]. / Nevrologicheskie oslozhneniya u patsientov s sakharnym diabetom 1-go tipa pri ispol'zovanii raznykh metodov insulinoterapii.

The study aims to examine the neurological complications of patients with type 1 diabetes treated with different methods of insulin therapy. MATERIAL AND METHODS: Thirty-four patients, aged from 18 to 40 years, with diabetes mellitus type 1 receiving insulinotherapy, with a duration of the disease 14.25±9.25 years, have been examined. By the time of the study the patients of the first group have been treated with continuous subcutaneous insulin infusion therapy (CSII) for 4.5±1.5 years following 11.3±5.4 years of standard basal-bolus therapy; the patients of the second group have been treated with basal-bolus insulin therapy for 12.7±7.7 years. RESULTS AND CONCLUSION: Neurological status and the presence of vegetative symptoms of the patients were assessed, following tests were performed: MMSE, MoCA, HADS, TSS, NSS, NDS. The results demonstrated that the patients from the group of CSII therapy have had less signs and symptoms of neuropathy, cognitive disorders and better emotional condition than the patients from the group of basal-bolus therapy.

[The results of the multicenter pharmaco-epidemiological observational project on the use of mydocalm in the treatment of pain syndromes with the muscle spasm].

The prospective multicenter open noncomparative pharmaco-epidemiological observational project on the use of mydocalm in real clinical practice has been completed in 2013. The project has been performed in 2090 clinical/rehabilitation settings in 284 cities of 13 countries using the results of 35,383 patients. The project aimed to assess the safety of treatment (percentage of patients with adverse-effects) and pain relieving efficacy as well as patient's satisfaction with the treatment. In total, 6603 (19%) adverse-effects were recorded. Their severity was evaluated as mild in 84,48%, no serious adverse-effects were noted. The high efficacy of mydocalm in the treatment of pain syndromes with the muscle spasm has been demonstrated. The high level of tolerability and absence of the clinically significant increase of adverse effects in the combination with nonsteroidal anti-inflammatory drugs have been confirmed.

[Efficacy of the combination drug vasobral in chronic vascular encephalopathy].

OBJECTIVE: Despite the high prevalence of chronic vascular encephalopathy, its diagnosis and treatment remain understudied. This observational multicenter trial assessed the efficacy and safety of vasobral in patients with cerebral ischemia. MATERIAL AND METHODS: The open observational study was carried out in 37 centers in 11 Russian cities and included 300 patients with confirmed diagnosis of chronic vascular encephalopathy, stages 1 and 2, without dementia. The patients received 1 tablet (4 mg α-dihydroergocryptine and 40 mg caffeine) 2 times a day during 3 months. RESULTS AND CONCLUSION: There was an improvement of cognitive and affective status as well as quality of life and a decrease of subjective signs of chronic vascular encephalopathy. Vasobral did not cause significant fluctuations of arterial pressure and was safe for patients with chronic vascular encephalopathy and arterial hypertension.

[The possibilities of increase of efficacy of rehabilitation of stroke patients with neglect syndrome].

OBJECTIVE: To evaluate different treatment schemes for post stroke patients with neglect syndrome (NS). MATERIAL AND METHODS: We studied management rules for patients with NS and the effect of ceraxon (citicoline) on the functional rehabilitation and removal of the neglect syndrome. We analyzed treatment results of 120 stroke patients. The functional rehabilitation was followed up using Barthel, Lindmark and Merton and Sutton scales, cognitive functions were assessed with the MMSE scale and the battery of frontal dysfunction, psychoemotional condition with the Beck Depression Questionnaire. Moreover, treatment efficacy has been evaluated by the absence of NS signs. RESULTS AND CONCLUSION: Maintenance of management rules and use of ceraxon improved the functional rehabilitation of stroke patients with NS.

Activity of succinate dehydrogenase in the neocortex and hippocampus of Mongolian gerbils with ischemic and reperfusion brain injury.

We analyzed changes in activity of SDH, one of the most important enzymes of the Krebs cycle, in the cytoplasm of hippocampal and cortical neurons of Mongolian gerbils (Meriones unguiculatus) at the early and delayed reperfusion period after global brain ischemia. The data indicate that SDH activity in pyramidal neurons of various hippocampal areas and in neurons of II, III and V layers of cerebral cortex after 7-min forebrain ischemia depends on both the localization of these neurons and duration of the postischemic reperfusion. SDH activity in neurons significantly increased on days 2 and 7 after reperfusion.

[The impact of early and late ischemic preconditioning on brain damage and degree of neurological deficiency in rats].

The present study was aimed to investigate neuroprotective effects of early and late ischemic preconditioning in the acute phase of ischemic brain damage in rats. It was found that a single five-minute ischemic episode of early ischemic preconditioning did not lead to significant neuroprotective effects in comparison with control group, while three five-minute ischemic episode early ischemic preconditioning accompanied by a significant increase in neurological deficit and growing damage rate in CA1 hippocampus neurons. In contrast, later ischemic preconditioning in form of single five-minute episode 24 hours before ischemia modeling, provided a significant neuroprotective effect, manifesting reduced neurological deficit and maintaining viability of CA1 hippocampus neurons.

[Molecular mechanisms of development of cerebral tolerance to ischemia (Review. Part 2)].

In the 2nd part the authors describe in details the main aspects of protective effect of preconditioning of the brain: inhibition of programmed cell death, weakening of phenomenon of excitotoxicity, activation of endogenous antioxidant systems, anti-inflammatory effects, modulation of glial cell function, changes in regional blood flow and vascular reactivity. In addition, data analysis on the impact of preconditioning on brain neurogenesis, the state of the blood-brain barrier, ion homeostasis and metabolism of neurons is presented. Review emphasizes the role of microRNAs in mechanisms of ischemic tolerance of brain. Profound understanding of molecular mechanisms of increased tolerance of brain to ischemic and reperfusion injury requires the implementation of this phenomenon in clinical practice.

[Molecular mechanisms of development of cerebral tolerance to ischemia. Part 1].

In the first part of this review molecular mechanisms of ischemic tolerance emerging as a result ofpreconditioning of the brain are discussed. Data on inductors, sensors, transducers and effectors of early and delayed ischemic tolerance are presented.

A new rat model of reversible global cerebral ischemia.

A new rat model of global cerebral ischemia-reperfusion was proposed via reversible occlusion of the major vessels originating from the aortic arch and supplying the brain. This technique can be used for the search and study of exogenous (pharmacological) and endogenous methods of brain protection from ischemia-reperfusion injury.

[Activity of lactate dehydrogenase in the brain cortex and hippocampus of Mongolian gerbils after global ischemia and reperfusion injuries].

Cerebral ischemia results in severe derangements of energy metabolism in the nervous tissue including activation of glycolytic pathway. Activity of cytosolic lactate dehydrogenase (LDH) in the specific brain structures remains unclear. The recent study was aimed at investigation into the LDH activity in the cytoplasm of both hippocampal and cortical neurons in Mongolian gerbils (Meriones unguiculatus) at different durations of reperfusion after global ischemia. Analysis showed that the activity of LDH in pyramidal neurons of various hippocampal areas and neurons of II, III and V cortical layers after 7-minute forebrain ischemia depended on both localization of the neurons and duration ofreperfusion. In general, the changes in postischemic cytosolic LDH activity include significant decrease in the LDH activity 2 days after reperfusion with varying degree of recovery on day 7 of reperfusion.

[Morpho-functional changes of hippocampal CA1 area in Mongolian gerbils after ischemic postconditioning].

The aim of this study was to determine the effect of ischemic postconditioning on hippocampal CA1 neuronal survival and cytoplasmic activity of lactate dehydrogenase (LDH) in the gerbil model of cerebral ischemia-reperfusion injury. Ischemia was induced by bilateral common carotid artery occlusion (for 7 min) in male Mongolian gerbils (Meriones unguiculatus). Ischemic postconditioning protocol comprised 3 cycles of 15 s reperfusion/15 s ischemia. After 48 h of reperfusion, CA1 neuronal death was detected by Nissl staining and the cytoplasmic LDH was demonstrated histochemically in CA1 area of the hippocampus with a quantitative cytophotometric assessment of the enzyme activity. The results have shown that 7 min ischemia resulted in a significant decrease in the number of viable neurons (up to 24%) in the CA1 area of hippocampus; in addition, it reduced the activity of LDH in these neurons (from 0.260 +/- 0.009 to 0.190 +/- 0.006 relative units). The application of ischemic postconditioning significantly increased the number of viable neurons (up to 52.9%, P < 0.01) in the CA1 area of hippocampus, and it was accompanied by an increase in the activity of LDH (0.240 +/- 0.008 relative units, P < 0.001).