[The chemoreactomic analysis of the central mechanisms of action of non-steroidal anti-inflammatory drugs]. / Khemoreaktomnyi analiz tsentral'nykh mekhanizmov nesteroidnykh protivovospalitel'nykh preparatov.

AIM: To perform a chemoreactome modeling of the pharmacological central effects of 4 non-steroidal anti-inflammatory drugs (NSAIDs): dexketoprofen, ketoprofen, aceclofenac, lornoxicam. MATERIAL AND METHODS: An analysis of the pharmacological spectrum of the central action of dexketoprofen, ketoprofen, aceclofenac and lornoxicam was based on the chemoinformatic approach, which compared drug-likeness properties with public and commercial software. RESULTS: The effectiveness of NSAIDs is related to the inhibition of cannabinoid receptors CB-1, the vanilloid receptor TRPV1, NMDA and AMPA receptors and of the GABA reuptake transporter, with dexketoprofen being the most effective inhibitor. The safety of the central effects of NSAID is due to weak interactions of the NSAIDs studied with opioid, adrenergic, serotonin and dopamine receptors. Chemoreactome modeling made it possible to compare the particulars of the effects of the studied NSAIDs on experimental pain and cramps. CONCLUSION: Inhibition of CB-1, TRPV1, NMDA, AMPA, GABA transporter by the NSAID molecules corresponds to a decrease in the intensity of nociceptive signals. A weak intervention of the studied NSAIDs in opioid, adrenergic, serotonin and dopaminergic neurotransmission corresponds to a decrease in the central side-effects of NSAIDs and to a lessened antagonism of these NSAIDs towards exogenous and endogenous opioids.

[Comparative studies of neurotrophic drugs based on brain hydrolysates]. / O sravnitel'nykh éksperimental'nykh issledovaniiakh neirotroficheskikh preparatov na osnove gidrolizatov golovnogo mozga.

The results of the analysis of comparative studies of neurotrophic drugs based on brain hydrolysates (BH) are presented. The most comprehensive comparative study of the BH drugs carried out by Zhang, et al. 2019 investigated the effects of four drugs (cognistar, cerebrolysate, cortexin, cerebrolysin) on a model of ischemic stroke in rats. The study showed that a significant improvement in the neurological outcome compared with placebo was observed only with cerebrolysin. Higher standardization in elemental composition, higher antioxidant activity, and presence of active peptide fragments of neuropeptides of nerve growth factor, enkephalins, orexin and galanin in cerebrolysin explains neurotrophic and neuroprotective effects of the drug.

[An analysis of epidemiological indices of stroke based on the data of a regional population register from 2009 to 2012].

OBJECTIVE: To study the dynamics of basic epidemiological sex- and age-related indices in the Russian Federation for 2009-2012. MATERIAL AND METHODS. The regions (administrative units, cities or city regions) with the population from 100 000 to 200 000 people were selected. The total population was 10 373 279 people. The indices were evaluated using the uniform method developed by the National stroke association. RESULTS: Incidence and fatality in men and women older than 25 years and able-bodied people (25-59 years) was analyzed using European standards. CONCLUSIONS: The incidence of stroke decreased regardless of sex and age from 2010 to 2012. There was a trend towards the decrease in fatality in men and women older than 25 years. Incidence and fatality were lower in women compared to men.

[Clinical efficacy and pharmacoeconomic characteristics of the neuroprotection with low doses of cortexin in the treatment of acute ischemic stroke].

OBJECTIVE: To assess the efficacy of the cytoprotective neuropeptide cortexin in the complex treatment in acute and early rehabilitation stages of ischemic stroke (II). MATERIAL AND METHODS: A multicenter prospective double-blind placebo-controlled trial has been carried out. Two hundreds and seventy-two patients with II have been enrolled in the trial. Cortexin was administered in low doses (10 mg three times a day intramuscular, using the following schemes: group 1: 2 courses of cortexin; group 2: 1 course of cortexin with the following course of placebo; group 3: two courses of placebo. The duration of treatment was 70 days. Patients were examined during 4 visits using clinical tests and instrumental methods. RESULTS: High efficacy and safety of cortexin in the complex treatment of patients with II has been shown. The best therapeutic effect was seen in group 1 (two 10-day courses of cortexin). The results were confirmed by the pharmacoeconomic analysis of treatment tactics based on the estimation of "net monetary benefit". CONCLUSION: Cortexin is recommended for treatment and rehabilitation of patients with II.

[Epidemiology of stroke in the Russian Federation: results of territory's population registry (2009-2010)].

An epidemiological study of stroke based on a territory's population registry, which is, according to WHO recommendations, a scientific basis of treatment organization and medical-social rehabilitation of stroke patients as well as stroke prevention, has been launched in the Russian Federation in 2009. Duration of the project is 5 years. Main epidemiological indices of stroke (morbidity, mortality and lethality) for 2009-2010 are presented. Morbidity of stroke was 3.52 and 3.27 cases per 1000 population in 2009 and 2010, respectively. Mortality was 1.19 and 0.96 per 1000. Significant differences in morbidity, mortality and lethality between different regions of the country were identified. The maximal morbidity was recorded in Chistopol (Tartar Republic) - 6.14 per 1000 and the minimal one in the Altai krai (1.39 per 1000). The decrease in the number of hemorrhagic stroke (HS) in 2009 was noted. The ratio of ischemic strokes to HS was 5:1 compared to 3.5:1 in the registry of 2001-2003. Neuroimaging methods (computed tomography and magnetic-resonance tomography) were used for differential diagnosis of stroke character in 63.1% of cases in 2009 and in 74.2% in 2010. There was 91.1% of stroke patients who received treatment in a hospital in 2010.

[Investigation of risk factors of cardiovascular events by the interregional assistance fund of relatives of stroke patients].

We have analyzed the results of the clinical and laboratory study of 1070 people in 7 regions of the Russian Federation, including 222 (20.7%) men and 848 (79.3%) women aged from 19 to 94 years (mean age 57.15±13.39 years). It has been shown that 6.8% were smokers and 31.5% were alcohol abusers. Regular physical training (>30 min/day) was noted in 45.7%. Symptoms of asthenia were found in 73.3%. The level of knowledge on risk factors of stroke was estimated as: arterial hypertension (68.6%), ischemic heart disease (47.5%), heart rhythm disorders (27.0%), thrombosis of low extremities (26.8%). Mean values of arterial pressure were 140/80 mm Hg, heartbeat rate -- 74 per min. Mean value of BMI was 28.67 kg/m(2), BMI was higher than 30 in 41%. Hyperglycemia >6.2 mmol/l was recorded in 28%, hypercholesterolemia >6.2 mmol/l in 26%. Stenoses of inner carotid arteries were found in 49.2%: less than 50% diameter stenosis was in 32.8%, 50--70% in 11.8% and >70% in 4.6%. Antihypertensive drugs were used by 66.8%, antiaggregants - by 31.2% and statins by 31.2%. Knowledge about stroke was demonstrated by 81.8%, about stroke symptoms -- 58.5%, about the appropriate actions to be taken in the case of a stroke -- 48.5%. The low risk of stroke was observed in 33.2%, moderate risk in 37.3%, high-risk in 24.6% and critical risk in 4.9%.

[The dynamics of the morbidity rate of stroke in the Dagestan Republic].

Results of the first epidemiologic survey of cerebral stroke in the Dagestan Republic (DR) carried out in 2009--2010 are presented. Using a population register, we evaluated the dynamics of the morbidity rate of stroke and effectiveness of primary and secondary prevention of stroke. There were 7533 cases of stroke, including 4116 in 2009 and 3413 in 2010. The morbidity rate per 1000 people was 2.76 in 2009 and 2.29 in 2010. The diagnoses were distributed as follows: ischemic stroke 3029 (73.6%) in 2009 and 2457 (72%) in 2010; hemorrhagic stroke -- 760 (18.5%) in 2009 and 692 (20.3%) in 2010; undifferentiated -- 327 (7.9%) in 2009 and 264 (7.7%) in 2010. Mean age at disease onset was 65.41±11.4 in 2009 and 66.43+12.6 in 2010. The measures for primary and secondary prevention of stroke performed in DR led to the reduction of stroke cases by 17% in 2010 compared to 2009.

[Cognitive functions in patients with stenosing lesion of brachio-cephalic arteries].

Authors studied cognitive functions in 97 patients with different clinical presentations, lateralization and number of stenotic brachio-cephalic vessels. The Luria's syndrome neuropsychological analysis distinctly revealed the topics of cognitive deficits. Wechsler verbal memory tests, the Stroop test (words-figures), the Schulte test were administered as well. Disturbances of high psychic functions were found in 97.9% of patients. The bilateral pathology of lobe regions was noted most often. The dysfunction of parietal and temporal lobes was mainly unilateral and was linked with the side of stenosing process. Disturbances of neurodynamic parameters of mental activity were correlated with the age (higher frequency in patients older than 50 years), a side of stenosis and/or lesion of stroke, bilateral lesions of carotid arteries. The results allow a more precise assessment of clinical significance of carotid stenosis in the development of cognitive dysfunction that may assist in recommendation of surgical treatment.

[Dynamics of higher mental functions and complications in the early post-operative phase of carotid endarterectomy].

Authors conducted a clinical-instrumental examination of 97 patients in the post-operative phase of reconstructive surgery of carotid arteries. Evaluation of neurological status, Luria's syndrome neuropsychological analysis for assessment of higher mental functions dynamics (HMF) were carried out. Pre-operative ultrasound duplex scanning of brachio-cephalic arteries and investigation of cerebral perfusion using spiral computed tomography (SCT-perfusion) were done before and 1 day after the surgery. The frequency of intrasurgery stroke in the area of the operated carotid artery was 2.1%. Pre-operative SCT-perfusion revealed the syndrome of cerebral hyperperfusion in 3.1% of patients with higher (>1 s) difference between the average time of blood transition in temporal areas. Dynamics of HMF was the key clinical indicator that allowed to evaluate the course of nearest post-operative phase and to compare it with an area of operated vessel. Changes of HMF were characterized by the decrease in dysfunction of the hemisphere ipsilateral to the side of operation or had differently directed character. The aggravation of HMF disturbances was found in 40% of patients and was represented by syndromes with different topical location. Causes and mechanisms of the development of these changes are discussed.

[Androgenic deficit and its treatment in stroke male patients with diabetes mellitus type II].

We have studied 154 men (mean age 61,4+/-4,1 years) with the first hemispheric ischemic stroke. Clinical and laboratory studies have revealed the androgenic deficit in 66,3%, with its frequency higher in patients with diabetes mellitus type II (50 and 26,3%, respectively). Forty-two men with diabetes mellitus type II and acquired androgenic deficit received replacing treatment with testosterone undecanoate in dose 1000 mg intramuscular. The treatment was started one week after the development of stroke, the next injections were given after 6 weeks and then every 12 weeks during 2 years. The control group included 30 males who did not receive androgens. After 2 years from the beginning of treatment, there were the decrease in clinical severity of androgenic deficit, the increase of total and free testosterone levels, and muscle power in the main group compared to the controls. Body mass index, glicated hemoglobin, cholesterol, triglycerides, low density lipoproteins have decreased as well. Secondary stroke has developed in 3 (7,1%) patients of the main group and in 5 (16,6%) controls; 12 (28,6%) patients returned to work in the main group compared to 2 (6,6%) in the control group. The treatment with androgens has a positive effect on risk factors of secondary ischemic stroke. It is an effective method for improvement of social adaptation of men survived after the stroke.

[The analysis of risk factors for acute stroke in Dagestan].

Results of the first epidemiologic survey of cerebral stroke in Dagestan carried out in 2009 using a method of population register are presented. Arterial hypertension was on the first place (98.5%) among risk factors. Other risk factors were determined as follows: cardiac diseases (24.2%), cardiac fibrillation (14.5%), lipid profile dysfunction (10.6%), smoking (8.7%), diabetes mellitus (8.6%), stress (7.5%), history of myocardial infarction (3.6%).

[Efficacy of cytoflavin in patients in the acute ischemic stroke].

We present the results of a multicenter study on efficacy of cytoflavin in the treatment of patients with acute ischemic stroke. Seventy patients (41 of the main group and 29 of the control group) were enrolled in the study. All patients received basic therapy aimed at improving systemic hemodynamics, rheological blood properties and at the prevention of stroke complications. Patients of the main group were treated with cytoflavin as follows: days 1-10 - 20 ml (in 400 ml of the 0,9% NaCl solution) twice a day intravenously in drops; days 11-35 - 850 mg twice a day. We assessed the dynamics of restoration of lost functions (NIHSS, the Rankin scale, the Barthel index) and volumes of ischemic lesion (MRI T1-, T2-, diffusion-weighted images). Results of the study on patients of the control group were supplemented with literature data about 306 patients studied using clinical scales and 40 patients studied with MRI. We revealed a trend towards an effect of cytoflavin on the preservation of brain matter in the acute phase of stroke. Cytoflavin reduced the neurological deficit and improved activities of daily living in patients that may be explained by the less brain damage.

[The effect of cerebrolysin in dosage 50 ml on the volume of lesion in ischemic stroke].

The purpose of this randomized, double-blind, placebo-controlled study was to assess safety and efficacy of cerebrolysin used in dosage 50 ml in acute ischemic stroke. Forty-seven patients with ischemic stroke, aged 45-85 years, who were admitted to a clinical unit within the first 12 h after stroke onset were included in the study. A quantitative time-related MRI analysis of the dynamics of neurological deficit revealed the more rapid decrease of stroke volume to the 28th day in the group treated with cerebrolysin (45.4% versus 43.6% in the placebo-group (p < 0.05)). No side-effects of treatment with cerebrolysin was found. The results of this prospective, randomized, placebo-controlled study suggest the positive effect of cerebrolysin on the dynamics of volume lesion in patients with ischemic stroke.

[Efficacy and safety of the combined therapy with citicholine and actovegin in the acute period of ischemic stroke].

One hundred and four patients with acute carotid ischemic stroke were included in the study. Patients were divided into 4 groups. Patients of control group (group 1) were treated with equal basic and reperfusional therapy without any cytoprotectors. Patients of the 2nd group received citicholine in dose 1000 mg per day. Patients of the 3rd group were treated with 250 ml actovegin per day. The NIH stroke scale, the modified Rankin scale and the Barthel index were used to assess neurological status dynamics. The significant decrease of neurological deficit and improvement of functional recovery were seen in patients treated both with citicholine and actovegin (p < 0.005) to the 30th day compared to the control group. There was a trend towards the decrease of brain infarction volume within 5 days after stroke in patients of the 4th group. No side-effects of citicholine and actovegin were found.

[Medical service to patients with stroke at the prehospital stage in different cities of the Russian Federation].

We have conducted a comparative analysis of medical service quality to stroke patients at the pre-hospital stage in Yuzhno-Sakhalinsk and Irkutsk. Periods of hospitalization, including periods of referral of patients (or their relatives) for medical care, arrival of ambulance personnel (AP), time spent by AP on the primary medical care and transportation of patients have been analyzed. We have analyzed periods of referral of people for medical care and assessed the volume and quality of pre-hospital therapy. The high percentage of hospitalization during the period of "therapeutic window" has been found in both cities with the significant prevalence in Irkutsk. The delay in hospitalization was caused by late referral of patients, low level of population awareness on importance of referral for urgent medical care besides the referral to AP. The number of patients transported to a hospital during the time interval (30-40 min) recommended by the WHO did not exceed 30-40% in both cities. Although the volume of medical care at the pre-hospital stage was larger in Yuzhno-Sakhalinsk, the quality of pharmacotherapy used by AP in Irkutsk was more in line with modern standards.

[Experimental hemorrhagic stroke: the study of neuropeptides (MIF, selank) in the intraperitoneal injection].

The aim of this study was to examine Taftsin derivates--macrophage inhibitory factor (MIF, Thr-Lys-Pro) and heptapeptide selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) in the model of experimental intracerebral hemorrhage in rats. The double autologous blood injection in the basal nucleus was used as a model of intracerebral hemorrhage. Animals ware randomly divided into three groups--the control group (n = 5) was treated with saline, the second group (n = 5) was injected with MIF in dose 150 mkg/ kg/day, the third group (n = 5) received Selank in dose 300 mkg/kg/day. Intraperitoneal injection of peptides was used. Body weight assessment, neurological examination and brain MRI were performed in 24, 72 hours and 10 days after the hematoma formation. The effect of neuropeptides on the functional restoration in animals, in the absence of the effect on hematoma volume and perifocal edema, was found. The significant reduction of perifocal edema and hematoma volume was observed in the 10th day after the hematoma formation in all experimental groups (p < 0.05). Only the control group of animals showed the significant (p < 0.05) weight loss in the 3rd day after the operation. The rate of neurological deficit was different: the significant improvement assessed with Menzes and limb placing test scales was seen only in the groups treated with neuropeptides in the 10th day.

[Comparative analysis of effectiveness of medical care service for patients with stroke in neurological and specialized departments for the treatment of patients with stroke].

A comparative analysis of effectiveness of medical care service for patients with stroke in neurological and a specialized departments for the treatment of patients with stroke has been carried out in the regional hospital. The specialized department had an intensive therapy block that made it possible to conduct twenty-four-hour monitoring of main parameters of vital functions and oxygenotherapy. Patients who were in need of artificial lung ventilation were placed to a department of general reanimation. In the end of the acute period, the level of disability significantly decreased in patients with ischemic stroke. The significant decrease of disability level was found in patients with ischemic as well as with hemorrhagic stroke after 3 months. The results suggest the higher effectiveness of therapy conducted in specialized departments.

[New possibilities of neuroprotection in the treatment of ischemic stroke].

A multicenter prospective double-blind placebo-controlled study was carried out in 62 patients with hemisphere ischemic stroke of atherothrombotic or cardiothrombotic character. Thirty-two patients, a main group, received intramuscular injections of cortexin, a domestic drug, in dosage 20 mg daily during 10 days from the first 6 hours from the development of symptoms of stroke, and 30 patients, a control group, received basic treatment and intramuscular injections of placebo in dosage 20 mg daily during 10 days. Patient's state was assessed before treatment and on 3rd, 7th, 11th and 28th days using the NIHSS scale for assessment of disease severity, intensity of focal neurologic deficit and dynamics of clinical parameters and the modified Rankin scale and Barthel index as a functional outcome measures. The data obtained suggest an efficacy of cortexin in the treatment of patients with acute ischemic stroke as compared to placebo. Safety of the drug was confirmed in the study.