Effect of mexidol on the efficiency of intravenous thrombolytic therapy for ischemic stroke during the therapeutic window

Author:
Knni K.S., Dyomin T.V., Adeeva L.B.
Interregional Clinical and Diagnostic Center, Kazan, Russia 12A, Karbyshev St., Kazan, Republic of Tatarstan 420101

Summary:
Objective: to evaluate the effect of intravenous mexidol on the efficiency of intravenous thrombolytic therapy (TLT) during the therapeutic window. Patients and methods. The retrospective study enrolled 123 patients with ischemic stroke (IS) who had undergone intravenous TLT in the vascular centers of the Republic of Tatarstan. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the time course of changes in their neurological status. According to the baseline severity of a neurological deficit, all the patients were divided into three subgroups: 1) mild IS (<8 NIHSS scores at admission); 2) moderate IS (>8 scores); and 3) severe IS (<16 scores). All the patients underwent X-ray computed tomography at admission, at 24 hours after TLT, and in case of worsening of their health status. Results. The prehospital use of mexidol followed by TLT in patients with IS had a positive effect on the regression of neurological deficit regardless of the severity of the disease. There were significant differences in the degree of regression of neurological deficit according to NIHSS at 24 hours and 10 days after hospital admission in patients with severe IS, who received intravenous mexidol at the prehospital stage and who did not take this drug before TLT. The pre-TLT use of mexidol contributed to higher regression of neurological deficit. There was a lower frequency of hemorrhagic transformations in the patients who used mexidol at the prehospital stage versus those who did not. Conclusion. The findings demonstrate the positive effect of mexidol on the efficiency and safety of TLT in patients with IS.

Keywords: ethylmethylhydroxypyridine succinate; intravenous thrombolytic therapy; ischemic stroke; neuroprotective therapy.

Experience with mexidol in neurological practice

Author:
O.A. GROMOVA, I.YU. TORSHIN, L.V. STAKHOVSKAYA, E.G. PEPELYAEV, V.A. SEMENOV, A.G. NAZARENKO

Federal Research Center «Informatics and Management», Institute of Pharmacoinformatics, RAS, Moscow, Russia; Research Institute of
Central Research Hospital of the Russian National Research Medical University. N.I. Pirogova, Moscow, Russia; FGBOU VO «Kemerovo
State Medical University» MH RF, Kemerovo, Russia; Federal State Autonomous Institution «National Medical Research Center for
Neurosurgery named after Academician N.N. Burdenko» of the Ministry of Health of the Russian Federation, Moscow, Russia

Summary:
Antihypoxic, antioxidant and nootropic effects of mexidol contribute to the improvement of patients with cerebrovascular pathology. The results of clinical studies show that the sequential scheme of using mexidol (first i.v. or i.m., then per os) is effective in the complex therapy of ischemic diseases of the brain, vascular surgery, therapy and rehabilitation of patients with degenerativedystrophic changes of the spine, treatment of neurodegenerative pathology (including multiple sclerosis, Parkinson’s disease and diabetic polyneuropathy), infectious neuropathies (ARVI, herpes, tick-borne encephalitis), neuropsychological and autonomic disorders.

Keywords: neurotransmission, GABA, acetylcholine, antihypoxants, nootropics, data mining, mexidol.

The efficacy of mexidol for transient ischemic attacks in the vertebrobasilar system in elderly patients with chronic cerebral ischemia

Author:
YU.V. ABRAMENKO
Tver State Medical University, Tver, Russia

Summary:
Objective. To evaluate the clinical efficacy, metabolic and membrane protective effects of mexidol for transient ischemic attacks (TIA) in the vertebrobasilar system in elderly patients with chronic cerebral ischemia (CCI). Material and methods. Fifty-three patients, aged from 60 to 74 years, with the first episode of TIA in the vertebrobasilar system and CCI were examined. Patients of the main group (n=33) received mexidol in the dose of 500 mg for 10 days along with standard therapy, patients of the comparison group (n=20) received only standard therapy. The clinical implications of TIA, laboratory indices of the state of oxidant and antioxidant systems and percentage absorption of lipid-phospholipid complexes in the infrared spectrum of blood serum were studied. The control group consisted of 20 healthy people. Results and сonclusion. The use of mexidol was associated with more rapid regression of the focal neurological deficit. Mexidol significantly reduced the intensity of lipid peroxidation and had a positive impact on the level of neuronal membrane phospholipids. Metabolic and membrane protective effects of mexidol and it’s positive impact on the regression of focal neurological deficit justify its inclusion into complex therapy of TIA in the vertebrobasilar system developed in patients with CCI, especially in elderly patients.

Keywords: transient ischemic attack, vertebrobasilar system, chronic cerebral ischemia, mexidol, lipid peroxidation, phospholipids.

Neuroprotection of cerebral accidents in ambulance phase

Author:
V. L. RADUSHKEVICH, A. I. OKUNEVSKY
Voronezh State Medical University n. a. N. N. Burdenko, Voronezh, Russia

Summary:
Relevance. Neuroprotection is a required component of intensive therapy of cerebral catastrophes on pre-hospital and hospital phases of care. The purpose of the study. Identification features and the effect of neuroprotection of different cerebral accidents. Materials and methods. For determination the level of knowledge and practical skills of neuroprotection of different cerebral accidents were conduct an anonymous voluntary questioning doctors Voronezh city ambulance station. The effectiveness of the use of neuroprotection of cerebral accidents was study by special protocols in practice on Voronezh ambulance station. The results. More good theoretical training believe 75 % doctors. Using mexidolum in complex intensive therapy on the prehospital neuroprotection of cerebral accidents has expressed a positive clinical effect.

Keywords: cerebral accident, neuroprotection, ambulance.

Oxidative stress and its pharmacological correction mexidol in traumatic brain injury

Author:
N.V. GOVOROVA
State budget institution of higher professional education «Omsk State Medical Academy» of Ministry for health care of Russia, Omsk, Russia

Summary:
Abstract. Examined and treated 114 patients with isolated severe head injury at the age of 18 to 55 years. Group I included 61 patients who survived, in group II — 53 patients who died on the 3–15th day post-traumatic period. Patients I and II groups had complex intensive therapy according to existing protocols. 15 patients (subgroup I1) was prepared in the complex therapy meksidol 1200 mg per day for 7–10 days. Against the background of mexidol decreased intensity of lipid peroxidation, maintained at a sufficient level power antioxidant defense system cells, there was an earlier resolution of post-traumatic encephalopathy and recovery of consciousness. The treatment mexidol noted more favorable during the early post-traumatic period, a reduction of complications (χ2=55,4; p<0,0001) — syndrome of acute lung injury, disseminated intravascular coagulation, acute cardiovascular failure, and pneumonia.

Keywords: traumatic brain injury, oxidative stress, mexidol.

Contemporary aspects of diagnostics and treatment of post-traumatic stress disorder in patients with brain injury

Author:
M.L. CHUKHLOVINA
State Pediatric Medical Academy, St. Petersburg

Summary:
Abstract. Thirty four patients (14 females and 20 males, 18 to 44 years old) with a post-traumatic stress disorder (PTSD) after mild brain injury were under observation. To perform scoring of cognitive functions and severity of anxious state, appropriate specific scales - Mini-Mental State examination – MMSE and Covi anxiety scale were employed. Levels of patients’ recovery motivation for their own disease were assessed with a special questionnaire (Recovery Locus of Control). Cognitive functions were decreased, showing mild to moderate disorders in patients with PTSD after brain injury. The levels of motivation for recovery from own disorder proved to be significantly decreased, and an inverse correlation was found between this parameter, and a degree of anxious condition in these patients. Treatment of the patients with Mexidolum improved cognitive functions, motivation, decreased the degree of anxious condition in PTSD. The results of study argue for a necessity of early detection PTSD after mild brain injury and inclusion of modern antioxidant and antianxiety drugs into combined therapy of the disease.

Keywords: post-traumatic stress disorder, brain injury, cognitive functions, anxious condition, Mexidolum.

Rehabilitation in stroke patients

Author:
V.V. KOVALCHUK, A.O. GUSEV

Summary:
The present article is devoted to the problems of the organization and carrying out of rehabilitation in post stroke patients. The features of stroke patient’s management with the help of multidisciplinary team are discussed. Main principles and rules of physical, psychotherapeutic and medication rehabilitation are reviewed.

Keywords: rehabilitation, stroke, multidisciplinary team, physical therapy, mexidol.

Alexithymia in patients with left-hemispheric cerebral infarction in the late recovery period

Author:
N.A. ANTONOVA, E.B. KUZNETSOVA, I.I. SHOLOMOV
Razumovsky Saratov State Medical University, Saratov

Summary:
Objective. To study emotional status, including alexithymia, anxiety and depression, in patients with cerebral infarction in the area of the middle cerebral artery (on the left side) in the late recovery period and to develop a method for correction of the damage. Material and methods. The study included 30 patients with cerebral infarction in the area of the middle cerebral artery (on the left side). A comparison group consisted of 10 patients with chronic brain ischemia. Results and conclusion. The results have demonstrated the correlation between the level of alexithymia and the severity of neurological deficit, sex-related level of anxiety and depression. The cerebral infarction impacts on the level of alexithymia. Alexithymia in patients with cerebral infarction affects the adequate self-esteem of physical and mental condition that may complicate the rehabilitation of these patients and demands correction as a combination of pharmacotherapy and psychotherapeutic intervention.

Keywords: alexithymia, cerebral infarction, anxiety, depression.

Modern methods of rehabilitation for poststroke patients

Author:
I.V. SIDYAKINA, M.V. VORONOVA, P.S. SNOPKOV, T.V. SHAPOVALENKO, K.V. LYADOV
Medical Rehabilotation Center, Moscow

Summary:
The article reviews the problem of complex post stroke rehabilitation. Special attention is drawn to neurorehabilitation aspect of patient’s state, restorative treatment in the acute stage of stroke, peculiarities of working up individualized rehabilitation programs, innovations and medicament support of rehabilitation process.
Keywords: stroke, rehabilitation, technical means of rehabilitation, medication support of rehabilitation process.

Side effects of psychopharmacotherapy in patients with the syndrome of dementia and the ways of its correction

Author:
S.N. DUMA

Summary:
The purpose of the study. Analysis of side effects of treatment with neuroleptics in patients with the syndrome of dementia of Alzheimer’s type. Evaluation of the effectiveness of the correction of side effects of treatment with neuroleptics with the additional use in the treatment of ethylmethylhydroxypiridine succinate (Mexidol®). Materials and methods. The study included 150 patients with Alzheimer’s disease with behavioral and psychotic disorders. The average duration of disease was 4.8 years. The average age of patients was 79,8±3,2 years. All patients received basic anti-dementia therapy for 2,6±1,4 years. Additionally patients were getting neuroleptic therapy within 4,2 ±1,2. The analysis of the character and intensity of the newly appeared side effects was based on the complaints of the relatives who were taking care e of patients and results of neurological examination. The comparative analysis of effectiveness of dose=reduction correction of side effects of neuroleptics was performed in two groups of patients. In the main group (n=76) the therapy included of Mexidol® 5,0–10,0 ml (250–500 mg), by parenteral route, No. 10–15. In the control group (n=74) the medicine was not administered. Evaluation of the effectiveness of treatment was based on a scale of Global Clinical Impression (CGI-I) after treatment. The results and conclusion. Side effects associated with neuroleptic therapy included the following most frequent and early appearing: reversible extrapyramidal disturbances such as akathisia and parkinsonism. They disappeared with a dose reduction of the antipsychotic medicine. While choosing pharmacotherapy it’s necessary to give preference to low doses of atypical neuroleptics. Additional parenteral therapy with ethylmethylhydroxypiridine succinate (Mexidol®) 5,0–10,0 ml (250–500 mg) No. 10–15 effectively (p<0,05) provides a more rapid reduction of side effects from neuroleptic therapy.

Keywords: Alzheimer’s Disease, dementia, psychotic symptoms, antipsychotics, Mexidol®.

The efficacy of mexidol in carotid endarterectomy procedure in patients with cerebral atherosclerotic stenosis

Author:
V.I. GOLOVKIN, A.V. SVETLIKOV, A.S. SHAPOVALOV, L.O. POPOVA
North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg

Summary:
Objective - to determine the antihypoxic efficacy of mexidol in carotid endarterectomy (CE) procedure in patients with cerebral atherosclerotic stenosis using cerebral oximetry. Material and methods. Clinical/psycho/neurological monitoring was performed in 109 patients with internal carotid artery stenosis of 69±7.0% and neurological symptoms of cerebral ischemia, 2-3 degree, in pre- and postoperative periods. Cerebral oximetry was carried out perioperatively. Fifty-four patients were treated with mexidol in a dose of 1000 mg/day for 14-15 days and 55 patients did not received mexidol. Results and conclusion. The difference in initial brain oxygenation (rSO2) between the main and comparison groups was shown (60.8±5.0 and 47.29±5.5%, respectively). During operation, the degree of blood oxygenation in these groups decreased by 57% and 41%, respectively. On day 7, significant differences in the Schulte test in two groups of patients with similar neurological status were found considering efficiency of work and mental stability before and after operation. No differences were found in the comparison group. Mexidol used for antihypoxic brain protection in carotid endarterectomy of patients with cerebral atherosclerotic stenosis significantly reduces the degree of cerebral hypoxia, decreases the duration of surgery, improves neurological status of patients and performance of psychological tests in postoperative period.

Keywords: cerebral stenosis, cerebral ischemia, carotid endarterectomy, cerebral oximetry, mexidol.

Efficiency mexidol in patients with endocrine polyneuropathy

Author:
E.B. KUZNETSOVA, I.I. SHOLOMOV, S.V. GERASIMOV, E.A. SALINA
Razumovsky Saratov State Medical University, Saratov; Clinical Hospital, Saratov

Summary:
Objective. To evaluate the efficacy of mexidol and necessity of using it in patients with endocrine polyneuropathies caused by primary hypothyroidism (PPHT). Materials and methods. We have examined 51 patients with confirmed diagnosis of PPHT and assessed their neurological status and indicators of metabolic homeostasis before and after treatment. Electroneuromyography (ENMG) was performed to assess the status of the peripheral nervous system. Results. The results indicate the presence of endocrine disorders of obligate metabolic homeostasis in patients with polyneuropathies. Antioxidants, in particular, mexidol, in a complex with other drugs can be used in the treatment of these disorders. Worsening of ENMG-parameters, demonstrating a trend towards the normalization in response to treatment antioxidants, are characteristics of this pathology. Conclusion. The efficacy of mexidol in patients with PPHT has been confirmed.

Keywords: endocrine polyneuropathies, metabolic homeostasis, mexidol, electroneuromyography.

Diagnosis and treatment of asthenic syndrome in elderly people after acute respiratory viral infection

Author:
I.E. POVERENNOVA, I.A. ZOLOTOVSKAYA, E.V. BEZGINA
Samara State Medical University, Samara; Samara City Policlinic, Samara; Medical X-Ray Center, Samara

Summary:
Objective: To study the characteristics of asthenic syndrome in elderly people after acute respiratory viral infection. Material and methods: We examined 87 patients with chronic cerebral ischemia and other comorbid disorders, aged from 63 to 78 years. Patients were randomized to two groups. Patients of the main group received mexidol (1 tablet (125 mg) 3 times a day during 3 weeks) along with standard treatment. Patients of the control group received standard treatment only. All patients underwent neuropsychological testing for the assessment of symptoms of asthenic syndrome. Results and Conclusion: A comparative analysis of the patient’s condition in both groups has demonstrated a reduction in symptoms of asthenia, autonomic lability and cognitive deficit in patients treated with mexidol.
Keywords: old age, asthenic syndrome, acute respiratory viral infection, treatment, mexidol.

Improvement of the efficacy of treatment of hypertensive encephalohathy by using mexidol

Author:
E.V. BOLOTOVA, N.YU. LUSHPAY, I.V. KOVRIGINA.
Kuban State Medical University under the Health Care Ministry of the Russia, Krasnodar, Russia; Reserch Institute - Territorial Clinical Hospital №1 med after Professor S.V. Ochapovski under the Health Ministry of the Russia, Krasnodar, Russia.

Summary:
Objective. To assess the efficacy and tolerability of mexidol used to improve cognitive impairment in patients with hypertension and clinical manifestations of chronic cerebral circulatory insufficiency. Material and methods. Forty-two patients with chronic cerebral circulatory insufficiency and cognitive impairment were examined. MMSE, МоСА and the clock drawing test were used to assess neuropsychological status. The Morisky-Green test was administered to evaluate medication adherence. Patients were stratified into two groups: patients of the first group (n=21) received standard treatment. Patients of the second group (n=21) received additionally mexidol in dose 200 mg (4 ml) in 100 ml of NaCl isotonic solution intravenously during 10 days and then in tablets (2 tablets 0,125 mg) twice a day during 8 weeks. Results. According to the 4-item Morisky Medication Adherence Scale (MMAS), 31% of respondents were not adherent to the treatment (MMAS score 0—2), 35.7% (n=15) of patients showed high adherence (MMAS score 4), 33.3% (n=14) demonstrated low adherence (MMAS score 3). The average score on the questionnaire was 2.85. In patients treated with mexidol, the absence of complaints increased by 3 times and headache regression increased by 90%. The improvement of memory, concentration and anxiety was observed in 50%, 55%, 67% of patients, respectively. Patients treated with mexidol demonstrated more significant changes during the clock drawing test. The average change in the scores increased by 0.95 compared to the control group, where the changes were 0.54 (p<0.02). The positive dynamics on MMSE and МоСА was shown in the mexidol group that indicated the positive effect of this drug on cognitive symptoms. Conclusion. The positive impact on cognitive symptoms and health in patients with chronic cerebral circulatory insufficiency allows to recommend mexidol as add-on to standard treatment of the main disease.

Keyword: mexidol, cognitive impairment, adherence.

Assessment of the efficacy of mexidol in the combination with hyperbaric oxygen in acute ischemic stroke

Author:
N.S. KULAI, E.YU. KOVALCHUK.
Saint-Petersburg I.I. Dzhanelidze research institute of emergency medicine, Saint-Petersburg, Russia.

Summary:
Objective. To study the efficacy of mexidol in the combination with hyperbaric oxygenation (HBO) in comparison with the standard HBO sessions in patients with acute ischemic stroke. Material and methods. One hundred and twelve patients were examined. In the main group, 48 patients underwent HBO and received treatment with mexidol. The control group consisted of 64 people who underwent the standard HBO sessions only. Results and conclusion. The use of combination therapy (HBO+mexidol) leads to the significantly more rapid normalization of acute phase indices which are correlated with neurological deficit reduction.

Keywords: ischemic stroke, hyperbaric oxygen therapy, mexidol.

The system stress-limiting action of mexidol in chronic cerebral ischemia

Author:
E.A. ANTIPENKO, A.V. DERUGINA, A.V. GUSTOV.
Nizhny Novgorod State Medical Academy of the Ministry of Public Health, Nizhny Novgorod; Lobachevsky Nizhny Novgorod State University, Nizhny Novgorod.

Summary:
Objective. To clarify the mechanisms of the action of anti-stress antioxidant agent (mexidol) in patients with chronic cerebral ischemia. Material and methods. Sixty-seven patients with chronic cerebral ischemia (TE stage II), 48 women and 19 men, mean age 48.2 years, were examined. To assess the state of multilevel stress system, the level of anxiety and depression, degree of autonomic imbalance, adaptive reactions of the blood and functional properties of erythrocyte membranes, level of average weight molecules in the blood plasma were studied. Therapeutic complexes consisted of standard therapy (vinpocetine and piracetam) and mexidol (10 ml intravenous drip 200 ml of physiological solution once a day every day for 10 days with subsequent transition to the oral ingestion of the drug (1 tablet (125 mg) 3 times a day for three months). Results and conclusion. In group 1 treated with additional antioxidant mexidol, the more pronounced and prolonged positive effect on the clinical symptoms of TE was observed. There were the persistent decrease in the level of anxiety and reduction of autonomic imbalance in the main group. The dynamics of adaptive reactions of blood indicated the activation of the adrenal cortex. There was a decrease in the content of average weight molecules and recovery of the sorption capacity of red blood cells. The results indicate the multi-component multi-level stress-limiting effect of mexidol in patients with chronic cerebral ischemia stage II.

Keywords: mexidol, chronic cerebral ischemia, treatment, stress.

An influence of submaximal (submineximal) doses of mexidol on oxidant stress and inflammation in the acute period of ischemic stroke

Author:
A.R. GODUNOVA, A.A. RAKHIMOVA, O.I. LEONTYEVA, I.G. TALIPOVA, R.M. YAKHIN, SH.G. MUSIN.
Emergency Hospital, Naberezhnye Chelny, Russia.

Summary:
Objective. To study an effect of submaximal doses of mexidol on the dynamics of biochemical markers of inflammation and damage to brain tissue in the acute period of ischemic stroke. Material and methods. A total of 60 patients admitted in the first 6h after disease onset with a verified ischemic stroke (7-9 points on the ASPECT scale) were enrolled in the study. Thirty patients in the study group received submaximal doses of mexidol: 750 mg infusion dropwise in 250 ml of 0.9% NaCl solution for 6 days. Thirty patients of the control group received standard therapy. Biomarkers and neurological status were evaluated within 60 minutes from the time of admission to the hospital and after 6 days. Results and conclusion. In both groups, the changes in CRP, IL-6, and fibrinogen did not contribute to the efficacy of mexidol. The brain natriuretic peptide (BNP) biomarker, plasma-A-associated pregnancy (PAPP-A) biomarker, average NIHSS score and mean cerebroasthenia score on the MFI-20 scale in the study group were significantly reduced compared to the control group. This study indicates a decrease in oxidative stress and signs of inflammation, a reduction of the severity of neurological deficit and an increase in physical activity of patients treated with submaximal doses of mexidol. Given the activation time of the damaged antioxidant system of the body, the recommended period of treatment is 3 months.

Keywords: antioxidant stress, inflammation, acute period, ischemic stroke, mexidol.

Тhе possibility of treatment of cognitive impairment in the complex therapy of patients with the consequences of cerebral infarction

Author:
Е.В. KUZNETSOVA, Е.А. SALINA, I.I. SHOLOMOV.
Saratov State Medical University of the Russian Health Protection, Neurology Chair.

Summary:
Objective. То study neuropsychological status of inpatients with the consequences of сеrеbrаl infarction treated with cortexin аnd mexidol. Material аnd methods. We carried out а neurological аnd neuropsychological examination of 62 patients with the consequences of cerebral infarction treated with cortexin in the dose of 10 mg and mexidol in the dose of 5 ml of 5% solution intravenously during 15 days. Results аnd conclusion. It has bееn shown that the use of this drug combination decreases complaints аnd neurological symptoms аnd significantly improves cognitive аnd emotional status as well. The more positive changes аrе related to attention, speed of mental reactions, anxiety аnd verbal activity. The complextherapy with cortexin аnd mexidol decreased neurological deficit аnd improve cognitive functioning and psychoemotional status thus increasing quality of life аnd rehabilitation potential of the patients.

Keywords: consequences of сеrеbral infarction, cognitive impairment, emotional status, cortexin, mexidol.

Modern strategies of protection of hypoxic-ischemic brain damage

Author:
S.N. YANISHEVSKY, N.V. TSYGAN, S.YU. GOLOKHVASTOV, R.V. ANDREEV, I.V. LITVINENKO, O.S. KARPOVA, V.A. YAKOVLEVA.
Kirov Military Medical Academy, St. Petersburg, Russia.

Summary:
Nowadays, there are two complementary approaches to treatment of patients with ischemic stroke: reperfusion and neuroprotection. The main purpose of neuroprotection is to intervene ischemic cascade at every stage of the pathological process and thus avoid the death of nerve cells and expand the therapeutic window for reperfusion therapy. The use of drugs with neurotrophic, antioxidant and neuroregenerative effects is pathogenically explained at all stages of post stroke rehabilitation. Ethylmethylhydroxypyridine succinate (mexidol) is a derivative of succinic acid with antihypoxic, membrane protective, nootropic, anticonvulsant and sedative action. The majority of researchers confirmed the positive effect of mexidol expressed as the marked regression of neurological deficit and wider opportunities for further early rehabilitation. The results of the randomized double blind multicenter placebo-controlled, parallel-group trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA) were published in 2017. The results of the study showed the best positive dynamics of neurological function recovery in case of timely treatment with mexidol with the following two month therapy. The safety of the long-term use of mexidol was confirmed.

Keywords: stroke, acute period, neuroprotection, succinate, efficacy of treatment, safety of therapy.

Тhе neuroprotective therapy of outpatient treatment of chronic cerebral ischemia

Author:
S.V. BEREZHNAYA, E.Z. YAKUPOV.
Kazan, Municipal health саrе «City hospital №6»; Kazan State Medical University.

Summary:
Objective. То perform а differential analysis of the efficacy of combination therapy bу the drugs with different modalities (mexidol, aescusan, halidorum) in outpatients with chronic cerebral ischemia (CCI), stages I-III. Material and methods. А study included 50 patients with CCI of atherosclerotic, hypertensive and mixed genesis (stage I-20, stage II-20, stage III-10 patients). In addition to somatic therapy, patients received three courses of mexidol, halidorum and aescusan combination therapy during 6 weeks with а 3 month interval between the courses. The changes in subjective complaints and objective clinical manifestations were evaluated after each course. Results and conclusion. The therapeutic efficacy after durable complex therapy bу repeated courses of antioxidants is supported bу the results of clinical and neurological examinations. Mexidol in the combination with aescusan and halidorum contributed to the improvement of cognitive, adaptive, motor functions of the patients with CCI, stages I and II. То increase treatment efficacy in patients with CCI, stage III, we recommend to use the drugs that improve cognitive functions of the patients.

Keywords: chronic cerebral ischemia, mexidol, combination therapy.

Results of a randomized double blind multicenter placebo-controlled, in parallel groups trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA)

Author:
L.V. STAKHOVSKAYA, N.A. SHAMALOV, D.R. KHASANOVA, E.V. MELNIKOVA, A.S. AGAFIINA, K.V. GOLIKOV, E.I. BOGDANOV, A.A. YAKUPOVA, L.V. ROSHKOVSKAYA, L.V. LUKINYKH, T.M. LOKSHTANOVA, I.E. POVERENNOVA, L.A. SHEPANKEVICH.
Pirogov Russian National Research Medical University, Moscow, Russia; Research Institute of Cerebrovascular Pathology and Stroke of Pirogov Russian National Research Medical University, Moscow, Russia; Interregional Clinical-Diagnostic Center, Kazan, Russia; City Hospital №26, St. Petersburg, Russia; City Hospital №40, St. Petersburg, Russia; City General Hospital №2, St. Petersburg, Russia; Kazan State Medical University, Kazan, Russia; Nikolaev Hospital, St. Petersburg, Russia; Vsevolga Clinical Interregional Hospital, Leningrad Region, Russia; Pirogov City Clinical Hospital №1, Samara, Russia; Seredavin Samara Regional Clinical Hospital, Samara, Russia; Research Institute Experimental and Clinical Medicine, Novosibirsk, Russia.

Summary:
Aim. To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS). Material and methods. A randomized double blind multicenter placebo-controlled, in parallel groups trial included 151 patients (62 men and 89 women) with hemispheric IS. Using a method of simple randomization, 150 patients (62 men and 88 women), aged 40-79 years, were randomized into two groups. Patients of Group I were treated with mexidol: 500 mg/day IV infusion for 10 days, followed by 125 mg tid (375 mg/day) PO for 8 weeks. Patients of Group II received the placebo according to the same scheme. The total duration of patients’ participation in trial ranged from 67 to 71 days. Results. By the end of treatment, the mean score on the modified Rankin scale (mRS) was lower in Group I compared to Group II (p=0.04). In Group I, the decrease in mRS mean score (Visit 1-5) was more prominent (p=0.023), percentage of patients with 0-2 scores by mRS scale (Visit 5) was higher (p=0.039), mean NIHSS score lower (p=0.035) in Visit 5 compared to group II. By the end of treatment, the decrease in mean NIHSS score in patients with diabetes mellitus was more prominent in Group I in comparison with Group II (p=0.038). In Group I, the dynamic of improvement of quality of life was more prominent and started from Visit 2 in general population and subpopulation of patients with diabetes mellitus. The share of patients with no problems with movement in space was higher in Group I (p=0.022). There were no statistically significant differences in frequency of side effects in patients of both groups. Conclusion. It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages.

Keywords: acute disturbances of cerebral circulation, mexidol, ethylmethylhydroxypyridine succinate, efficacy and safety, ischemic stroke, acute period, acute rehabilitation period, EPICA.

The results of the study of the efficacy and safety of mexidol in patients with chronic cerebral ischemia

Author:
E.I. CHUKANOVA, A.S. CHUKANOVA, KH.I. MAMAYEVA.
Pirogov Russian National Research Medical University, Moscow.

Summary:
Objective. To analyze the efficacy and safety of mexidol and their effect on the dynamics of neurological signs of the disease, emotional status and quality of life in patients with chronic cerebral ischemia (CCI). Material and methods. We studied 45 patients with CCI who received mexidol in dose 500 mg a day during 14 days by introvenal introduction with the following peroral administration in doses 500 mg twice a day during 60 days. A comparison group included 30 patients with CCI matched for age, risk factors and severity of neurological symptoms, who did not receive mexidol. Patients of both groups received standard treatment that included medications needed for the complete correction of the risk factors. Cognitive function (MMSE), movement activity and quality of life (SF-36) were assessed. Results. To the end of the study (74th day), a decrease in the severity of movement disorders, normalization of SF-36 scores and improvement of mean values of screening-assessment of cognitive function were identified in patients of the main group compared to those of the comparison group. Conclusion. The high efficacy and safety of treatment of CCI patients with mexidol using.

Keywords: chronic cerebral ischemia, oxidative stress, movement disorders, depression, quality of life, mexidol.

Contemporary paradigm of rational stroke treatment

Author:
S.A. ZHIVOLUPOV, YU.S. BUTAKOVA, I.N. SAMARTSEV.
Department of nervous diseases of the Military Medical Academy; primary vascular compartment Novodvinsk City Hospital, Saint Petersburg, Russia.

Summary:
Stroke was and remains one of the world’s leading medical and social problems. Nowadays we are watching permanent sometimes cardinal changes in view about etiology, pathogenetic mechanisms and therapy of patients with stroke. In this work there have been elucidated contemporary theoretical and practical aspects of stroke treatment and prophylaxis based on the results of multicenter clinical trials and experience of leading foreign and native specialists. Much attention is devoted to the pharmacotherapy of patients with stroke. It is showed that application of neuroprotective drugs is of great importance, among which antihypoxants with pleiotropic action play a crucial role (mexidol).

Keywords: stroke, therapy, prophylaxis, neuroprotection, antihypoxants, mexidol.

Possibilities of antioxidant therapy for asthenia and cognitive deficit in elderly patients with chronic brain ischemia

Author:
S.N. DUMA.
Research Institute of Therapy, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk.

Summary:
Aim. To evaluate the effect of the antioxidant mexidol on the oxidant-antioxidant potential of low-density lipoprotein (LDL), asthenic and anxious symptoms, and cognitive function of neurodynamic type in elderly patients with chronic brain ischemia (CBI). Subjects and methods. Thirty women (mean age 66.7 years) with grade 1-2 dyscirculatory encephalopathy (DE) were examined. Trends for asthenic, anxious, and cognitive symptoms of neurodynamic type were estimated using the standard tests (MFI-20, Hamilton Anxiety Rating Scale, Schulte Tables, Wechsler test) on days 1, 15, and 60 of mexidol treatment (for 60 days). LDLs were isolated from blood by heparin precipitation. The baseline level of lipid peroxidation products was determined and the concentrations of fat-soluble antioxidants (α-tocopherol, retinol, β-carotene, and xanthins) were examined in the isolated LDLs on days 1 and 5 of the study. Results. A 60-day mexidol therapy cycle statistically significantly caused a reduction in asthenic and anxious symptoms in elderly patients with CBI and induced positive changes in the symptoms of cognitive neurodynamics. Assessing the specific features of the pharmacodynamics of the antioxidant mexidol used in the elderly patients for 15 days revealed a statistically significant positive effect on the oxidative potential of LDLs as a decreased predisposition to their antioxidative processes in vivo. The drug’s effect in elevating the levels of α-tocopherol and β-carotene was altered insignificantly (without statistically significant changes), which reflects the pharmacodynamic features of the drug in the elderly patients. Conclusion. The 60-day cycle of therapy with the antioxidant mexidol has a positive impact on asthenic and neurotic symptoms in the elderly patients with CBI. Mexidol is well tolerated and safe when used long.

Keywords: asthenia, anxiety, cognitive defect, chronic brain ischemia, elderly age, specific features of antioxidant therapy, mexidol.

Optimization of hypolipidemic therapy in patients with ischemic stroke and diabetes mellitus

Author:
L.A. SHCHEPANKEVICH, YU.A. NIKOLAEV, N.A. DOLGOVA.
Research Institute of Experimental and Clinical Medicine, Novosibirsk.

Summary:
Objectives. Evaluation of effectiveness of Mexidol in optimization of hypolipidemic therapy in ischemic stroke and diabetes mellitus patients. Material and methods. Authors analyzed the indicators of lipid status: total cholesterol, low-density lipoproteins, high density lipoproteins, triglycerides and concentration of platelet factor-4, β-tromboglobulin, von Willebrand factor in 68 patients with acute ischemic stroke and diabetes mellitus. Authors investigate the dynamics of these parameters (1st, 21st, 3-d and 6th month after onset stroke) depending on timing and dose of Mexidol. Results. Long time therapy of Mexidol may optimize of hypolipidemic therapy in ischemic stroke and diabetes mellitus patients.

Keywords: ischemic stroke, diabetes mellitus, comorbidity, lipids, hemostasis, mexidol.

Chronic cerebrovascular diseases associated with metabolic syndrome: new treatment approaches

Author:
M.M. TANASHYAN, O.V LAGODA, K.V. ANTONOVA.
Nevrology Research Center Russian Academy of Medical Sciences, Moscow.

Summary:
Metabolic syndrome is a risk factor for acute and chronic cerebrovascular diseases. The development of oxidative stress promotes the progression of cerebral ischemia and treatment of the biochemical disturbances is needed. Use of antioxidants in patients with cerebrovascular diseases and metabolic syndrome reduce such symptoms as insulin resistance, hyperglyceridemia, hyperglycemia. The authors present results of a clinical study of mexidol in 40 patients, aged from 50 to 70 years, with chronic cerebrovascular pathology. Perspectives of using this group of drugs as universal neuroprotectors are discussed.

Keywords: ischemic cerebrovascular diseases, antioxidant treatment, metabolic syndrome, mexidol.

Neurometabolic therapy in secondary prevention of stroke

Author:
V.V. KOVALCHUCK.
Semashko City Hospital №38, St. Petersburg.

Summary:
Objective. To study the efficacy of mexidol in secondary prevention of stroke. Material and methods: We analyzed 3400 patients with stroke which were stratified into 7 groups: patients with cryptogenic ischemic stroke (II), arterial hypertension, atrial fibrillation, metabolic syndrome, syndrome of sleep-induced obstructive apnea/hypnea, diabetes mellitus, vasculitis. The assessment of efficacy was based on the absence of repeated II within 5 years of therapy. Results. Mexidol reduced the frequency of repeated II both in patients without concomitant diseases and in those with arterial hypertension, syndrome of sleep-induced obstructive apnea/hypnea, vasculitis, diabetes mellitus, atrial fibrillation and metabolic syndrome. Conclusion. The reliable efficacy of mexidol in secondary prevention of stroke was found out.

Keywords: stroke, secondary prevention, mexidol.

Adaptogenic effects of mexidol in chronic cerebral ischemia

Author:
E.A. ANTIPENKO.

Summary:
The data on the effect of the succinate-containing antioxidant mexidol on the adaptation abilities of patients with chronic brain ischemia are presented. We studied 98 patients with discirculatory encephalopathy of I, II and III stages. A set of indices for psychoemotional status, functional state of the brain, autonomic status, nonspecific stability to hypoxia, adaptive reactions of the blood system and status of antioxidant defense have been used to evaluate adaptive abilities of the body. It has been shown that the introduction of the antioxidant in the treatment set strengthens the effects of basic treatment by increasing adaptive reserves of the body in stages I and II of disease that is related with the realization of reactions of urgent adaptation. The introduction of mexidol in the treatment set increases the frequency of favorable outcomes after one year of follow-up.

Keywords: brain ischemia, discirculatory encephalopathy, adaptation, adaptogenic effect, stress.

The use of succinates for the correction of metabolic disorders in the penumbra in patients with stroke

Author:
M.M. ODINAK, S.N. YANISHEVSKII, N.V. TSYGAN, S.YU. GOLOKHVASTOV, I.A. VOZNIUK, A.G. TRUFANOV.
Kirov Military Medical Academy, St. Petersburg.

Summary:
The aim of the study was to determine the quantitative content and correlation between metabolites in the core ischemic zone, the ischemic penumbra and the intact tissue of the opposite hemisphere in the acute stage of ischemic stroke using MR-spectroscopy. We studied 72 patients, including 37 patients (the main group) treated with the antioxidant mexidol (2-ethyl-6-methyl-3-hydroxypiridine succinate) in addition to standard therapy and 35 patients who received standard therapy only. The severity of stroke was assessed using the NIHSS. The Barthel index and Rankin scale were used to evaluate functional outcome in the 30th day, hydrogen MR-spectroscopy was used twice: in the first 24 h from disease onset and in the 5th day. Mexidol used in dose 500 mg intravenously during 14 days reduced significantly the content of lactate (p=0.002) and inositol (p=0.005) in the cells compared to the control group that enhanced the restoration of the balance between aerobic and anaerobic mechanisms of oxidation and positively influenced on the rehabilitation of patients. Positive correlations between the content of lactate in the ischemic penumbra and NIHSS scores (r=0.5786; p=0.049) and the negative correlation between the content of lactate in the ischemic penumbra and the degree of functional restoration assessed by the Barthel index (r= –0.6305; p=0.028) were found. These findings support the evidence for the interaction between the disturbance of glucose metabolism in conditions of hypoxia and the degree of nervous tissue damage.

Keywords: ischemic stroke, magnetic resonance spectroscopy, antioxidants, mexidol (2-ethyl-6-methyl-3-hydroxypiridine succinate).

The assessment of the clinical efficacy, vasoactive and metabolic effects of mexidol in elderly patients with discirculatory encephalopathy

Author:
YU.V. ABRAMENKO.

Summary:
Forty patients, aged from 55 to 74 years, with chronic cerebral ischemia — discirculatory encephalopathy, stages I—II, against the background of arterial hypertension and atherosclerosis were studied. Patients were randomized into 2 equal groups. Patients of the main group received the antioxidant mexidol intramuscular in dose 100 mg during the first 10 days and then perorally in dose 125 mg three times a day during 20 days in the combination with the regular treatment (diroton in dose 5-20 mg daily, cardiomagnyl in dose 75 mg daily). Patients of the control group received regular treatment during 30 days. The efficacy was evaluated at baseline, on the 10th and 30th days after the treatment using clinical scales (the number of complaints, neurological deficit, cognitive and emotional disorders), parameters of cerebral hemodynamics measured with transcranial duplex scanning, laboratory indices of the state of oxidant and antioxidant systems (the content of malonic dialdehyde and superoxide dismutase in the blood plasma as well as the plasma total antioxidant activity). The statistically significant (p<0.05-0.01) reduction in the severity of asthenic and anxiety disorders, the improvement of static-locomotor and cognitive functions as well as of parameters of cerebral hemodynamics due to the decrease in the peripheral vascular resistance and the normalization of venous outflow from the cavity of scull was seen in patients treated with mexidol compared to the baseline and the control group. Mexidol significantly reduced the intensity of lipid peroxidation and increase the total antioxidant activity of the blood. The results obtained in the study allow to consider mexidol as the effective drug in the complex treatment of discirculatory encephalopathy in elderly patients.

Keywords: chronic cerebral ischemia, discirculatory encephalopathy, antioxidants, neuroprotectors, mexidol.

Efficacy of mexidol in the combination with thrombolytic therapy in patients with ischemic stroke

Author:
Zh.Yu. CHEFRANOVA, T.A. MAKOTROVA, V.A. UDACHIN, E.V. KOLEDINTSEVA

Summary:
Comparative efficiency of ethylmethylhydroxypyridine succinate (Mexidol) in combination with thrombolytic therapy in patients with ischemic stroke was studied in 116 patients. All patients divided into 2 groups: group (46 patients) received thrombolysis with mexidol and group (70 patients) received thrombolysis with standard therapy. These results showed that the synergy this one therapy leads to significantly faster normalize acute indicators, which correlated with the degree of reduction the neurological deficiency. Thus, the results showed that the synergistic therapy creates the conditions not only for the restoration of neurological status, but also to prevent secondary brain damage.

Keywords: ischemic stroke, mexidol (ethylmethylhydroxypyridine succinate), combination with thrombolytic therapy.

Changes in the hemostasis system and free-radical lipid oxidation in the acute stage of ischemic stroke in patients on neuroprotection treatment

Author:
G.I. IZHBULDINA

Summary:
We examined 163 patients with primary ischemic stroke admitted within the first 12 h after stroke onset. Neurological status on the Orgogozo scale and blood test results (lipid spectrum, level of free-radical lipid oxidation measured with chemiluminescent method, hemostasis system parameters) were estimated at admission and on the 21th day of stroke. Patients were stratified into 3 groups: group 1 (n=59) received traditional treatment and mexidol during the first 10 days in dose 500,0 mg intravenously and cerebrolysate in dose 1,0 ml intramuscular; group 2 (n=60) received cerebrolysate in dose 1,0 ml intramuscular during 10 days in addition to traditional treatment; group 3 (n=44) received only traditional treatment. At baseline, patients with ischemic stroke demonstrated the increase in blood plasma atherogenicity (p<0,05), intensity of free-radical lipid oxidation and thrombogenic potential of blood that were correlated with disease severity. Administration of neuroprotective drugs mexidol and cerebrolysate in addition to complex treatment of stroke improved the lipid spectrum, reduced the intensity of free-radical lipid oxidation, stabilized hemostasis parameters. The increase in survival rate and more rapid reversal of neurological deficit in patients of group 1 were identified to the 21th day.

Keywords: ischemic stroke, lipid spectrum, free-radical process, hemostasis, neuroprotective therapy, mexidol, cerebrolysate.

The randomized double-blind placebo-controlled study of efficacy and safety of mexidol in the complex therapy of ischemic stroke in the acute period

Author:
V.I. SKVORTSOVA, L.V. STAKHOVSKAYA, YA.R. NARTSYSSOV, M.K. BODYKHOV, I.V. KICHUCK, YU.V. GUDKOVA, T.D. SOLDATENKOVA, T.T. KONDRASHEVA, E.V. KALININA, M.D. NOVICHKOVA, O.B. KERBIKOV.

Summary:
The first randomized double-blind placebo-controlled study of efficacy of mexidol has been conducted. Fifty-one patients with ischemic stroke, aged 45-85 years, admitted during the first 24 hours after stroke were switched to mexidol in dosage 300 mg daily during 14 days. Twenty seven patients received the placebo using the same scheme. The significant forward dynamics in regress of neurological disturbances on the NIH scale was found to the 14th day in patients treated with mexidol as compared to the placebo group (p<0.05), along with functional rehabilitation assessed according to the dynamics of clinical scores on the Bartel scale to the 21st day after stroke (p<0.05) in patients involved in the study during the first 6 hours after disease onset. The normalization of functional brain activity was revealed in patients receiving mexidol, in comparison with the placebo, i.e. during the acute pharmacological test. A study of the antioxidant system demonstrated the increase of enzyme activity (superoxide dismutase, glutathione peroxidase, glutathione reductase) and the analysis of enzyme activity of the respiratory mitochondrial chain revealed the increase of succinate dehydrogenase activity in patients receiving mexidol. The results confirm the clinical efficacy of mexidol in the acute period of ischemic stroke in the carotid system of atherothrombotic or cardioembolic pathogenetic types, especially for its earlier (up to 6 hours) prescription, and specify mechanisms of its action (antihypoxic, antioxidant) in clinical conditions.

Keywords: ischemic stroke, mexidol.

Neuron specific enolase as a measure of the efficacy of mexidol in patients with neurologic complications of primary hypothyroidism

Author:
E.B. KUZNETSOVA
Razumovsky Saratov State Medical University, Saratov

Summary:
Objective. To evaluate the activity of neuron specific enolase (NSE) in patients with primary hypothyroidism (PGT) treated with mexidol. Material and methods. Patients with PGT (n=110) were examined before and after treatment. Neuropsychological and neurological status of the patients was studied. To assess the status of the peripheral nervous system, electroneuromyography was performed and serum NSE level was determined. Results and conclusion. The NSE activity depended on gender, age of the patient, duration of endocrinopathy and presence/absence of neurological symptoms. The clear positive dynamics of the majority of the parameters studied was noted during mexidol treatment. The efficacy of antioxidant therapy in these patients was confirmed.

Keywords: neurological complications, primary hypothyroidism, neuron specific enolase, electroneuromyography, mexidol.

Cerebrovascular diseases: perspectives of pathogenetic metabolic correction treatment

Author:
M.M. TANASHYAN, O.V. LAGODA, K.V. ANTONOVA
Research Centre of Neurology, Moscow, Russia

Summary:
Metabolic syndrome is a serious risk factor for acute and chronic cerebrovascular disease, which are a leading cause of disabling conditions. The association of proatherogenic effects of the main components of metabolic syndrome - hyperinsulinemia, arterial hypertension, dyslipidemia and obesity - leads to prominent haemorheological and hemostasis changes, which in turn play a pivotal role in the initiation, course and outcome of cerebrovascular pathology. Metabolic syndrome also influences the efficacy of the main pathogenetic therapy of cerebrovascular diseases — antithrombotic therapy. Thus, primary and secondary prevention of cerebrovascular disease in patients with metabolic syndrome should include haemangiocorrective, antithrombotic, antioxidant and endothelium-protective treatment, as well as therapy of the main components of metabolic syndrome.

Keywords: cerebrovascular disease, metabolic syndrome, haemorheology and haemostasis, antithrombotic therapy, antioxidants.

Specific features of neurological complications developing in patients with type 2 diabetes mellitus and metabolic syndrome: Possibility for correction and prevention

Author:
V.N. SHISHKOVA
Center for Speech Pathology and Neurorehabilitation, Moscow Healthcare Department, Moscow, Russia

Summary:
The prevalence of type 2 diabetes mellitus (DM) and preceding metabolic disturbances has reached epidemic proportions. Oxidative stress plays a significant role in the development of micro- and macrovascular complications in patients with DM. The accumulation of free radicals is responsible for the development of systemic and vascular inflammation, endothelial dysfunction, and hypercoagulable and ischemic states. Since vascular and nervous system damages do not level off even under adequate glycemic control, there is a need for complex pathogenetic treatment strategies. Antioxidant therapy using mexidol is one of the compulsory components of combination therapy for complications of DM.

Keywords: type 2 diabetes mellitus, metabolic syndrome, oxidative stress, mexidol.

Cognitive impairments as a universal clinical syndrome in a therapist’s practice

Author:
V.N. SHISHKOVA
Center for Speech Pathology and Neurorehabilitation, Moscow Healthcare Department, Russia

Summary:
The problem of cognitive dysfunctions in patients with somatic diseases occupies a prominent place now since they are one of the most common manifestations of organic brain lesions. The early detection of potentially cured cognitive impairments is one of the important tasks of a present-day therapist, cardiologist, endocrinologist, and family doctor as the patients with early-stage cognitive impairments constitute the majority of those who have sought medical advice. In the modern world, primary health care physicians’ actions are decisive in predicting the development of dementia since the detection of early non-dementia forms of cognitive impairments and neuroprotective therapy with mexidol in particular are frequently quite sufficient to considerably reduce the degree of the impairments and to improve the prognosis of dementia.

Keywords: cognitive impairments, dementia, mexidol.

Neuroprotection in hypertensive patients: Minimization of poor prognosis

Author:
V.N. SHISHKOVA
Center for Speech Pathology and Neurorehabilitation, Moscow

Summary:
The paper discusses approaches to optimizing pharmacotherapy in patients with hypertension associated with cerebrovascular diseases. Possible indications for neuroprotectors and a pathogenetic rationale for their mechanism of action in patients with prior cerebral stroke are detailed.

Keywords: cerebral stroke, hypertension, neuroprotection.

An experience with neuroprotective therapy of primary open-angle glaucoma based on the use of different dosage forms of Mexidol

Author:
E.S. LEONOVA1, 2, S.V. POLYAKOV1, 2, М.А. POZDNYAKOVA2, Е.P. YARYGINA3, S.О. SEMISYNOV2
1Railway Clinical Hospital on the Station Gor’kiy, JSC Russian Railways, Inter Railway Center of Ophthalmology, 18 Lenina prospect, Nizhny Novgorod, Russian Federation, 603140; 2Nizhny Novgorod State Medical Academy, 10/1 Minina i Pozharskogo Sq., Nizhny Novgorod, Russian Federation, 603950; 3Nizhny Novgorod City Hospital No. 35, City Center of Glaucoma, 15 Osharskaya St., Nizhny Novgorod, Russian Federation, 603005

Summary:
Aim - to develop an algorithm to guide neuroprotective therapy in railway workers undergoing long-term follow-up for primary open-angle glaucoma (POAG) judging from the efficacy of sequential administration of intravenous dosage form of Mexidol and oral tablets. Material and methods. All sorts of JSC Russian Railways employees with stage I-III POAG and well-controlled intraocular pressure were enrolled. Mexidol was first to be administered intravenously by a dropper in a day hospital (250 mg daily for 5 days) and then taken orally at home (125 mg t.i.d. for 3 months). A comprehensive ophthalmic examination with hightechnology control was performed in all patients at their first, second, and third follow-up visits. Results. Data from 58 patients (96 eyes) were analyzed. Statistically significant improvements in perimetry and optical coherence tomography results were only obtained at a third visit, i.e. at the end of the course of Mexidol tablets. The treatment effect was most pronounced in stage I-II patients. Conclusion. The results suggest that combination therapy with intravenous and oral Mexidol received sequentially as well as long-term (3-month) administration of Mexidol tablets can both be recommended in POAG patients. It has been also found that neuroprotective therapy with Mexidol performs best for early stages of the disease.

Keywords: glaucoma, neuroprotective therapy, Mexidol, long-term follow-up.

Antioxidant agents in neuroprotection treatment of glaucoma

Author:
E.A. EGOROV1, A.A. GVETADZE1, N.G. DAVYDOVA2
1The Russian National Research Medical N.I. Pirogov University; 2Helmholtz Moscow Research Institute of Eye Diseases

Summary:
Purpose was to study efficiency and safety of mexidol in combined therapy in patients with primary open-angle glaucoma (POAG). 94 patients (185 eyes) at the age of 18—75 years old with POAG I—III stages were divided into 3 groups: 50 patients received combined therapy of mexidol 100 mg and picamilon 150 mg, 22 patients received combined therapy of mexidol 300 mg and picamilon 150 mg, 22 patients received only picamilon 150 mg. All medicine was administered qd during 14 or 21 days. Examination included standard ophthalmologic methоds, perimetry, electroretinography, retinal and optic nerve heard arterial blood flow. Improvement of visual acuity, perimetric, electrofisiological indicies and increased blood flow velocity of central retinal artery were registrated. Combined mexidol therapy allows improving results in treatment of patients with POAG.

Keywords: Mexidol, picamilon, primary open-angle glaucoma, glaucomatous optic neuropathy, optic nerve heard.

The influence of water soluble antioxidant agent (mexidol) on optic nerve and blood flow velocity in ocular and orbital arteries in patients with primary open-angle glaucoma

Author:
I.A. VOLCHEGORSKY1, E.V. TOUR1, O.V. SOLYANNIKOVA1, V.S. RYKOUN1, E.V. BERDNIKOVA1, M.S. SUMINA2, V.N. DMITRIYENKO2
1Chelyabinsk State Medical Academy; 2Chelyabinsk Regional Clinical Hospital

Summary:
The prospective single-blind placebo-controlled randomized trial is devoted to influence of mexidol (2-ethil-6-methil-3-hydroxipiridine succinate) on dynamics of optic nerve electrophysiologic profile and velocity indices of blood flow in ocular and orbital arteries in correlation with changes of retinal photosensitivity, visual acuity and visual field size during course of intravenous mexidol infusions and standard treatment of primary open-angle glaucoma. 2 weeks of intravenous infusions of 300 mg mexidol daily was found to cause depression of optic nerve electrical sensitivity threshold and widening of total visual field (16 mm2 test stimulus) after 14 days of treatment. These effects were not associated with changes of blood flow velocity in ocular and orbital arteries, were transient and came to initial indices 3 months after the end of treatment. Delayed vasotropic effect of mexidol manifested in increase of blood flow velocity in central retinal artery in 90 days after the end of infusions.

Keywords: mexidol, primary open-angle glaucoma, blood flow velocity in ocular and orbital arteries, optic nerve sensitivity.

Mexidol in complex treatment of glaucoma

Author:
E.A. EGOROV, N.G. DAVYDOVA, I.A. ROMANENKO, N.D. NOVIKOVA
FGU «MNII GB named after Gelmgoltsa Rosmedbiotechnology»
Department of Ophthalmology of Medical Faculty
GBOU VPO RNIMU Russian National Research Medical University
Moscow

Summary:
Purpose: to evaluate efficiency and safety of Mexidol solution in complex treatment in patients with POAG of I–III stages. Materials and methods: patients with POAG I–III stages with compensated IOP level (not more than 21 mmHg) were included into the study. All patients were divided into 3 groups: in 1st group Mexidol was prescribed on the background of standard treatment by 100 mg per day intramuscularly, in the 2nd group – on the background of standard treatment by 300 mg per day intramuscularly, 3rd group received standard treatment (picamilonum – by 1 tablet 3 times per day). Patients with I–II stages of glaucoma received treatment during 14 days, with III stage – 21 days. Evaluation of treatment effect was carried out in 30 days after it’s start. External eye examination, visometry, biomicroscopy, ophthalmoscopy, tonometry, computer perimetry, electrophysiologic examination, arterial pressure and heart rate measurements were proceeded on the first, intermediate and last control visits. Results: Visual acuity was improved in 1st and 2nd group more evidently than in the 3rd one. There was a tendency of improvement of the condition of the visual field (decreasing of the scotoma amount in patients which received Mexidol by 100 mg per day). Increased at the beginning electrosensitivity threshold in patients with I–III stages of glaucoma reduced by the end of the study, and decreased level of the electrical lability of optic nerve raised. Dosage of 300 mg per day was found more efficient than 100 mg per day. Conclusion: Mexidol could be recommended for inclusion into the complex treatment of patients with glaucomatous neuropathy.

Usage of Mexidol in patients with dystrophic diseases of posterior eye segment

Author:
E.A. EGOROV, B.V. OBRUCH, A.I. OLEINIK, L.S. BORDASHEVSKAYA, M.R. KURBANOVA
Department of Ophthalmology, GOU VPO Russian State Medical University of Roszdrav Municipal Clinical Hospital 15, named after Filatov

Summary:
Purpose: to evaluate the efficacy of Mexidol in patients with glaucomatous optic neuropathy. Materials and methods: 139 patients with glaucomatous optic neuropathy were divided into 3 groups: 45 patients received Mexidol, 46 – combined treatment by Mexidol, Treantal, Kavinton and Solcoseryl, 48 – were included in the control group. Examination was carried out before treatment and in 10 days after the beginning: evaluation of visual acuity, retinal light sensitivity, perimetry, retinotomography. Results: Visual acuity increased by 0.05–0.2 in 41 patients of the first group. Average peripheral visual field enlarging by 60–110 degrees was found in 35 patients. In 38 patients light sensitivity of the retina improved
by 3–5.9. In the second group improvement of visual acuity was detected in 39 subjects by 0.05–0.3, peripheral field enlargement– by 80–140 degrees in 41 patients and light sensitivity by 4.71 – in 42 patients.

Conclusion: Combined treatment including Mexidol allows achieving better results in treatment of patients with glaucomatous optic neuropathy.

Arterial hypertension, cognitive disorders and dementia: a view of a cardiologist

Author:
O.D. OSTROUMOVA, M.S. CHERNIAEVA
Moscow State University of Medicine and Dentistry named after A.I. Evdakimov, Moscow, Russia; I.M. Sechenov First Moscow State
Medical University, Moscow, Russia; Central State Medical Academy of Department of Presidential Affairs, Moscow, Russia

Summary: 
This article presents a review of Russian and foreign literature about the impact of arterial hypertension (AH) on the risk of cognitive impairment and dementia. Large studies have demonstrated the effect of blood pressure (BP) on the risk of vascular dementia and Alzheimer’s disease (AD) in elderly and oldest old people as well as a role of antihypertensive therapy. There is evidence of a negative effect of hypertension in middle age on cognitive functions in late-life. Observational studies as a whole have shown the positive effect of antihypertensive therapy on the prevention of cognitive function and dementia. However, there are a number of limitations that dictate the need for further research on this issue. The importance of the interdisciplinary approach to treatment of cognitive impairment by cardiologists and/or therapists, together with neurologists, as well as complex treatment regimens, including correction of risk factors and neuroprotective therapy, is highlighted.

Keywords: arterial hypertension, cognitive impairment, dementia, Alzheimer disease, antihypertensive therapy.

Clinical aspects of ethylmethylhydroxypyridine succinate in elderly patients with cardiovascular pathology

Author:
Martemianova E. G.1,2
1LLC «Preobrazhenskaya Clinic». Ekaterinburg; 2LLC «IC Bivita». Ekaterinburg, Russia

Summary:
Aim. To evaluate efficacy and safety of original ethylmethylhydroxypyridine succinate (Mexidol) in cardiological patients ≥75 year old. Material and methods. In the observational study, according to ethical standards of Khelsinki Declaration, with informed consent, 24 patients participated, age 75-88 y. o. Inclusion criteria: age ≥75 y. o.; already diagnosed coronary heart disease (CHD) and/or chronic heart failure (CHF); Mexidol usage. Exclusion criteria: absent informed consent, severe comorbidities. Mean age of the patients at inclusion 80,33±4,06 y. o.; 16 (66,7%) females and 8 (33,3%) males. Patients consequently visited office of cardiologist with the diagnoses: chronic CHD (I25.0-I25.9), CHF with preserved systolic function (I50.0-I50.9). All patients were consulted by neurologist, had an established diagnosis of cerebrovascular disease (I65-67). To reduce the symptoms of frailty, among the neurologist recommendations, with accordance to routine clinical practice, the original Mexidol was included. Mexidol was prescribed by a scheme of manufacturer: intravenous infusions 500 mg x 5 days, then per os 125 mg t. i.d.; overall treatment — 8 weeks. Results. Statistically significant results were noted in 6 months from the study start. There was significant increase of 6 minute walking distance in men from 304,00±87,09 to 388,63±92,28 m (р=0,01), in women from 346,06±56,81 to 427,69±76,87 m (р=0,003); also there were less signs of frailty. No one patient showed significant worsening of the condition; during the overall follow-up, patients did not call emergency or primary care physicians and did not hospitalize. Conclusion. In comorbidity patients aged ≥75 y. o. at Mexidol treatment, there was increase of 6-minute walking test distance, decrease of asthenia signs, that witness for the medication efficacy. All patients showed good tolerability of the drug that witness for safety. Obviously, there are broad trials needed to sum up a gerontological algorithm of CHD and CHF patient management in outpatient setting.

Keywords: Mexidol, heart failure, frailty.

Cytoprotective therapy for kidney injury in patients with ST-elevation myocardial infarction

Author:
N.YU. BOROVKOVA1, A.S. ILYINA1, A.A. SPASSKY2, N.N. BOROVKOV1, G.V. KOVALEVA3
1Federal State Budgetary Educational Establishment of Higher Training «Nizhny Novgorod state medical academy» of the Ministry of Public Health; 2Federal State Budgetary Educational Establishment of Higher Training «The Pirogov Russian National Research Medical University» of the Ministry of Public Health; 3State Budgetary Institution of Health Nizhny Novgorod region «Nizhny Novgorod Regional Clinical Hospital named after NA Semashko»

Summary:
Aim. To study an effectiveness of mexidol (ethylmethylhydroxypyridine succinate) for kidney injury in patients with ST-elevation myocardial infarction (STEMI). Material and methods. The study involved 55 STEMI patients. Acute renal injury (ARI) was determined according to basal creatinine, serum creatinine, glomerular filtration rate, cystatin C and NGAL. In STEMI patients standard therapy was supplemented by antioxidant (cytoprotector) mexidol from the 1st to the 10th day 750 mg/day intravenously. ARI values were assessed after treatment. Results. There were 36 ARI patients among 55 patients with STEMI. Therapy with mexidol significantly decreased ARI severity (urine creatinine, cystatin C and NGAL values) after 48 hours. Conclusion. Mexidol may be used in addition to standard therapy in STEMI patients to reduce ARI severity.

Keywords: cytoprotectors, myocardial infarction, acute renal injury.

Mexidol influence on the parameters of infrared spectrometry of blood lipid complex in case of acute coronary syndrome

Author:
L.V. SHPAK, G.M. ZUBAREVA, S.N. LEBEDEVA
Tver State Medical Academy, Department of Internal Medicine and Department of Chemistry, FPAE

Summary:
It was analyzed the mexidol influence on phospholipid metabolism in acute coronary syndrome (ACS). The study included 70 patients. Intravenous mexidol infusions were included in the complex therapy in 30 cases. Conventional clinical and laboratory data, as well as the absorption of lipid phospholipid complexes in the infrared spectrum of blood serum were evaluated. The study established a mechanism of phospholipids autoregulation as a wave-like fluctuations of their concentration in the blood serum with early increasing (compared with healthy) in the first hours and days of development of ACS. It was observed the maximum rise by the 4th day and a moderate decline by the 10 day of observation reflecting the degree of adaptation systems stress. Regardless on the clinical form of ACS mexidol application eliminates oscillatory nature of the phospholipids dynamics. It is stabilizing their rise at a level sufficient to ensure the power and plastic needs of the organism and myocardium that improves the results of combined treatment.

Keywords: acute coronary syndrome, homeostasis, phospholipids, mexidol, infrared spectrometry.

Antioxidant therapy in the correction of oxidative stress in the patients with coronary heart disease and type II diabetes

Author:
O.A. GORYUSHKINA, E.M. VASILYEVA
Voronezh State N.N. Burdenko Medical Academy

Summary:
Abstract: the paper describes the study of the state of LP0‐AOD system in the patients with coronary artery disease and type 2 diabetes and the effect of antioxidant therapy on metabolic factors. Timely correction of disorders contributed to the positive dynamics of metabolic processes, and on the background of this, reduced frequency of cardiovascular complications.

Keywords: LP0‐AOD system, coronary artery disease, type II diabetes, antioxidant therapy, cardiovascular complications.

Mexidol in comlex therapy of a stable angina

Author:
G.I. NECHAEVA1, S.D. KUROCHKINA2, A.D. TROTSENKO3, E.U. BULACHOVA2

Summary:
It is carried out research of quality of life and alarm at 130 patients with stable angina FC II conditions of policlinic branch BUZOO City Clinical Hospital 4 Omsk. We have studied functional parameters at sick by a stable angina, influence of disease on quality of life. We have studied efficiency of preparation Mexidol in complex treatment of patients with a stable angina. We have developed the differentiated approach to pharmacotherapy in view of quality of life and a level of alarm of person.

Keywords: ischemic heart disease, stable angina, quality of life.

Role of antioxidants in treatment and prevention of patients with high risk of cardiovascular complications

Author:
L.A. SHCHEPANKEVICH, M.M. TANASHYAN, YU.A. NIKOLAEV, V.YA. POLYAKOV, M.A. PERVUNINSKAYA, K.V. ANTONOVA
Research Institute of Experimental and Clinical Medicine, Novosibirsk, Russia; Neurology Research Center, Mosсow, Russia

Summary: 
Aim — to estimate effect of Mexidol on blood lipids in patients with high cardiovascular risk and diabetes mellitus type 2 (DM2). Material and methods. Two groups of patients with DM2 as the main risk factor of vascular complications were prospectively followed-up within 3 months. Achievement of target blood lipid was compared in standard therapy with statins (group 1) and addition of Mexidol to basic therapy (group 2). Enzymatic colorimetric method was used to determine blood lipids level (Boehringer Mannheim, Germany). Results. There was a positive effect of Mexidol at the initial stage of statins therapy that was expressed by normalized lipids level in DM2 patients with high and very high cardiovascular risk.

Keywords: cardiovascular complications, diabetes mellitus type 2, dyslipidemia, prevention, Mexidol.

Characteristics of anxiety in patients of older age groups with different types of mild cognitive disorder

Author:
A.P. SIDENKOVA
Urals State Medical University, Ekaterinburg, Russia

Summary:
Objective. To study the structure of anxiety symptom complex in patients of older age groups with amnestic, disregulatory and polymodal types of mild cognitive impairment (MCI) and determine the clinical efficacy of 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol). Material and methods. Thirty-two patients over 55 years of age with MCI (ICD-10 item F 06.7) seeking medical help due to anxiety were included in the study. Inclusion criteria were the compensation of concomitant diseases, absence of relevant stressful events during the last year, absence of depression. Clinical-psychopathological method and psychometric scales (HAM-A, GDS, MMSE, CGI-S, CGI-I) and a stressful life events list were used. Reduction of the total score on the HАМ-А was the main criterion of the efficacy of 4-week treatment with mexidol (375 mg daily). Results and conclusion. At baseline, mean scores on the HAM-A and MMSE were 39,9+3.18 and 25.7+0.6 respectively. The study of the anxiety structure in patients with amnestic, disregulatory and polymodal types of MCI revealed the different phenomenology of anxiety symptom complex. Repeated assessment of anxiety on the HAM-A was performed on 1, 2 and 4 week of treatment with mexidol. The improvement of mental state was noted in all types of MCI but the better results were obtained in disregulatory and polymodal types. The rate of anti-anxiety effect was higher in the disregulatory type of MCI. In all patients, mexidol improved attention stability and autonomic function.

Keywords: anxiety in the elderly, mild cognitive disorder, neuropsychological types MCI, comorbidity MCI and anxiety, mexidol.

Dynamics of eeg and psychophysiological indicators of acute poisoning neurotoxicants on the stage of rehabilitation on the background of different methods of treatment

Author:
I.YU. BEREZINA, A.V. BADALYAN, L.I. SUMSKY, YU.S. GOLDFARB
Sklifosovsky Research Institute for Emergency Medicine, Public Healthcare Institution of Moscow Healthcare Department, Moscow, Russia;
Russian Medical Academy of Postgraduate Education, Federal Public Educational Institution of Additional Professional Postgraduate Education of Russian Federation Healthcare Ministry, Moscow, Russia

Summary:
Objective: To evaluate the dynamics of functional activity of brain structures underlying cognitive functions in patients with encephalopathy due to poisoning with neurotoxicants on the stage of rehabilitation. Material and methods: Fifty-six patients were examined. The main group consisted of 40 patients treated with intravenous injections with mexidol (n=10), combination of mexidol with non-pharmacological methods – mesodiencephalic modulation (MDM) (n=10), hyperbaric oxygenation (HBO) (n=10) and the combination of MDM and HBO (n=10). The comparison group included 16 people. All patients underwent neurophysiological (EEG, auditory event-related potentials) and neuropsychological examinations. Results: Marked EEG changes were noted in all patients. The domination of disturbances of functional activity on the diencephalic or mesodiencephalic levels was observed. After treatment, positive changes were found in 60% of patients. The positive dynamics was observed in 80% patients when the combination of mexidol, MDM and HBO was used. The negative dynamics was noted in 5 (12,5%) of patients of the main group, in particular when mexidol only was used. The results of the primary neuropsychological study revealed that cognitive impairment of different severity was found in 97,5% of patients of the main group and 100% of patients of the comparison group. After treatment, performance on neuropsychological tests improved by 62,5%, N200 and P300 latencies reduced, while the amplitudes increased, in the patients of the main group. Conclusion: The use of mexidol, MDM and HBO in the treatment of patients with encephalopathy due to poisoning with neurotoxicants on the stage of rehabilitation improved the indicators of functional brain activity and cognitive functions.

Keywords: encephalopathy, acute poisoning with neurotoxicants, electroencephalography, auditory event-related potential (P300), psychophysiological testing, mexidol, mesodiencephalic modulation, hyperbaric oxygenation.

The effect of mexidol in the combination with antidepressants on sleep disturbance in young patients with panic disorder

Author:
E.S. KURASOV, R.S. REMIZEVICH
Kirov Academy of Military Medicine, St.-Petersburg

Summary:
We studied 70 patients with panic disorder, 30 men and 40 women, mean age 34,5±1,8 years. All patients had insomnia. Patients were classified into the main and control groups. Patients of the control group received antidepressants only (fevarin in dosage 150 mg daily). Patients of the main group were additionally treated with mexidol (375 mg daily). The treatment duration was two weeks. A clinical and instrumental (polysomnography) examination revealed that the use of mexidol enhanced the decrease in anxiety disorders, autonomic disturbances and insomnia and improved quality of life of the patients.

Keywords: panic disorder, antidepressant, mexidol.

Mexidol as additional therapy for the patient with continuous paranoid type of schizophrenia in the in the presence of a late dyskinesia

Author:
A.L. DYAKONOV

Summary:
At a moderate late dyskinesia at patient with continuous paranoid type of schizophrenia receiving treatment with haloperidoli and cyclodoli with addition of mexidoli leads to easing of the undesirable phenomena. The most positive results is revealed on scales AIMS, BARS. Indicators of a scale of SAS on additional inclusion of mexidoli reacted to a lesser degree.

Keywords: mexidol, late dyskinesia.

Preventive therapy with mexidol in toxic damage to the heart

Author:
M.D., ASSOCIATE PROFESSOR E.I. POLOZOVA
Ogarev Mordovia State University, Saransk, Russia

Summary:
The purpose of this study was to efficacy of mexidol in the prevention of toxic damage to the heart in acute pancreatitis. Material and methods. The paper presents the results of experimental studies conducted on 30 adult mongrel adult dogs, which simulated acute focal pancreatic necrosis. We studied the influence of mexidol in the complex therapy for changes in the qualitative and quantitative composition of the lipid tissue structures of the heart, the intensity of processes of lipid peroxidation, antioxidant capacity, phospholipase A2 activity and morphofunctional state of the heart muscle in experimental acute focal pancreatic necrosis. The results and discussion. The preventive use of antioxidant drug mexidol in complex treatment of acute focal pancreatic necrosis, which limits the development of endogenous intoxication, increased intensity of lipid peroxidation and restores antioxidant capacity, reduces leading to phospholipase activity in tissue structures of the heart, corrigiruet lipid metabolism and morphofunctional state of the heart, and, consequently, toxic damage to the heart during endotoxic.

Keywords: pancreatitis, endogenous intoxication, heart, mexidol, antioxidant system, lipid.

The efficacy of mexidol in carotid endarterectomy procedure in patients with cerebral atherosclerotic stenosis

Author:
V.I. GOLOVKIN, A.V. SVETLIKOV, A.S. SHAPOVALOV, L.O. POPOVA
North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg

Summary:
Objective - to determine the antihypoxic efficacy of mexidol in carotid endarterectomy (CE) procedure in patients with cerebral atherosclerotic stenosis using cerebral oximetry. Material and methods. Clinical/psycho/neurological monitoring was performed in 109 patients with internal carotid artery stenosis of 69±7.0% and neurological symptoms of cerebral ischemia, 2-3 degree, in pre- and postoperative periods. Cerebral oximetry was carried out perioperatively. Fifty-four patients were treated with mexidol in a dose of 1000 mg/day for 14—15 days and 55 patients did not received mexidol. Results and conclusion. The difference in initial brain oxygenation (rSO2) between the main and comparison groups was shown (60.8±5.0 and 47.29±5.5%, respectively). During operation, the degree of blood oxygenation in these groups decreased by 57% and 41%, respectively. On day 7, significant differences in the Schulte test in two groups of patients with similar neurological status were found considering efficiency of work and mental stability before and after operation. No differences were found in the comparison group. Mexidol used for antihypoxic brain protection in carotid endarterectomy of patients with cerebral atherosclerotic stenosis significantly reduces the degree of cerebral hypoxia, decreases the duration of surgery, improves neurological status of patients and performance of psychological tests in postoperative period.

Keywords: cerebral stenosis, cerebral ischemia, carotid endarterectomy, cerebral oximetry, mexidol.

To efficiency of the use of mexidol for patients by a chronic pancreatitis in the stage of intensifying

Author:
LYSENKO S.G.,
PhD of Biological Sciences, Associate Professor of department of biology of the Luhansk National university, Luhansk
KHOKHLOVA A.V.,
Master’s degree of department of Biology of the Luhansk National university, Luhansk
DEMIDENKO V.V.,
Manager by a surgical separation, Surgeon of higher category of the Luhansk municipal multi-field hospital 3, Luhansk

Summary:
Abstract. Studied the problems of treatment and modern prophylaxis for the patients of suffering a chronic pancreatitis. Influence of mexidol is analysed on the biochemical indexes of blood, glucose of blood. Proved, that mexidol applied in a complex with standard therapy, able to influence reparative processes in a pancreas. On the basis of undertaken a study it is suggested to apply mexidol authors additionally with basic therapy, for patients by a chronic pancreatitis, with the purpose of facilitation of flow of this disease and decline r risk of development of complications requiring an.

Keywords: chronic pancreatitis; mexidol; amylase; thymol test; urea; blood glucose; treatment; preventive maintenance; reparative.

Increase of relaparotomy efficacy in peritonitis manapement

Author:
A.P. VLASOV, E.K. SALAKHOV, O.YU. RUBTSOV
N.P. Ogarev Mordovia State University

Summary:
Keywords: relaparotomy, peritonitis, abdominal sanitation, enteral lavage, mexidol.

Effect of mexidol on physical working efficiency and level of lactat in blood rats in conditions of light desynhronizes

Author:
T.A. ZAMOSHCHINA, A.A. GOSTYUKHINA, K.V. ZAITSEV, M.V. SVETLIK, O.B. ZHUKOVA

Federal state budgetary institution «Siberian Federal science-clinical center of Federal medicobio-logical agency», Seversk, Russia; Siberian
State Medical University SSMU, Tomsk, Russia

Summary:
Objective. To study an effect of mexidol on the performance of rats after light or dark deprivations in the swimming test with a load and to evaluate the state of glycolytic processes under these conditions. Material and methods. The experiment was carried out in the spring on 70 Wistar male rats. Three groups (30 animals) were in natural light conditions. One of them was not affected. The other two groups were subjected to exercise and 30 minutes before it either saline or mexidol was administered intramuscularly. Four other groups (40 animals) for 10 days were under conditions of dark or light deprivation prior to the presentation of physical activity and received either saline or mexidol before the test after deprivation was canceled. A forced swimming test with an additional load, which was presented to animals every day at 10—11 am for five days in a row, was used as a model of physical activity. The level of lactate was determined by colorimetric method. Results and conclusion. Mexidol increased the performance of rats in the swimming test, both under natural lighting conditions and with light desynchronization, contributed to the formation of cross adaptation to physical activity under natural lighting conditions and prolonged this state under conditions of light deprivation, did not change the content of lactate in the blood of rats after exercise in natural lighting conditions and dark deprivation and prevented its rise after light deprivation.

Keywords: mexidol, light and dark deprivation, working capacity, lactate.

Influence of mexidol and hemisuccinate 2-ethyl-6-methyl-3-hydroxypyridine on cerebral hemodynamics at hemorrhagic and ischemic damage of brain

Author:
I.N. KURDYUMOV1, T.S. GAN,SHINA1, D.V. MASLENNIKOV1, E.V. KURZA1, A.A. GORBUNOV1,2, A.I. TURILOVA1 and R.S. MIRZOYAN1

1 V.V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, ul. Baltiiskaya 8, Moscow. 125315 Russia

2 I.M. Sechenov First Moscow State Medical University (Sechenov University), ul. Trubetskaya 8, Moscow, 119881 Russia

Summary:
Comparative study of the effect of mexidol and hemisuccinate 2-ethyl-6-methyl-3-hydroxypyridine on the cerebral circulation of rats under conditions of hemorrhagic and ischemic brain lesions revealed significant differences in their cerebrovascular effects. Mexidol at a dose of 200 mg/kg i.v. better improves the local cerebral blood flow in modeling ischemia as compared to hemorrhagic brain damage. Hemisuccinate 2-ethyl-6-methyl-3-hydroxypyridine at a dose of 50 mg/kg better enhances the local blood supply to the cerebral cortex under conditions of hemorrhagic brain damage as compared to ischemic damage, since its cerebrovascular effect during cerebral ischemia occurs in a dose of 100 mg/kg. The mechanism of cerebrovascular anti-ischemic effect of 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate is mediated by GABAa receptors of the brain vessels, since bicuculline eliminates this effect.

Keywords: mexidol; hemisuccinate 2-ethyl-6-methyl-3-hydroxypyridine; bicuculline; cerebral circulation; hemorrhagic stroke model; global transient ischemia.

An effect of mexidol on the expression of the transcription factor Nrf2 in cerebral cortex in ischemia

Author:
E.N. YAKUSHEVA, P.YU. MYLNIKOV, I.V. CHERNYKH, A.V. SHCHULKIN.
Ryazan State Medical University, Ryazan, Russia.

Summary:
Objective. To study an effect of the antioxidant and antihypoxant mexidol (ethylmethylhydroxypyridine succinate) on the transcription factor Nrf2 expression in neuronal nucleis of frontal cortex cells autor the common carotid artery unilateral occlusion. Material and methods. The study was performed on 64 male Wistar rats. The Nrf2 expression was determined immunohistochemically. Results. Single intraperitoneal mexidol (120 mg/kg b.w.) infusion and oral (100 mg/kg p.w. thrice a day for 14 days) administration of mexidol did not affect Nrf2 expression. Unilateral common carotid artery occlusion led to the increase in Nrf2 expression 4 h and 5 days after occlusion. Oral administration of mexidol in dose of 100 mg/kg b.w. thrice a day for 14 days before and after ischemia increased Nrf2 expression on the 4th h and on the 12th day in comparison with intact animals. Nrf2 expression was higher after 4 h and 12 days in comparison with the control occlusion group. Conclusion. Mexidol increases Nrf2 expression in the frontal cortex of rats not under normal conditions but in common carotid artery unilateral occlusion.

Keywords: mexidol, Nrf2, ethylmethylhydroxypyridine succinate, ischemia, occlusion, common carotid artery.

The study of the neuroprotective effect of mexidol on the cellular model of glutamate stress

Author:
O.A. GROMOVA, I.YU. TORSHIN, E.V. STELMASHUK, O.P. ALEXANDROVA, A.V. PRONIN, I.V. GOGOLEVA, L.G. HASPEKOV
Federal Research Center «Informatics and Cybernetics», RAS, Moscow, Russia; Scientific Center of Neurology, Moscow, Russia; Ivanovo State Medical Academy of the Ministry of Health of Russia, Ivanovo, Russia

Summary:
Purpose of the study. Study of neuroprotective properties of mexidol on a cellular model of glutamate stress. Material and methods. Cytological studies were carried out under the conditions of the model of glutamate stress in the culture of granular neurons of the cerebellum. Results. The addition of mexidol to the cultural medium increased the survival of neurons by 8-10% after the addition of glutamate (p<.05). The effect of mexidol was more pronounced when applied at the stage of growing the culture of neurons (5 days), when the survival of the cells in conditions of glutamate stress increased by an average of 20%. The conclusion. The results of the study confirm the direct neuroprotective effect of mexidol in the culture of neurons under the conditions of the glutamate stress.

Keywords: cellular stress, excitotoxicity, glutamate, mexidol.

Comparative chemoreactome analysis of mexidol

Author:
I.YU. TORSHIN, O.A. GROMOVA, I.S. SARDARYAN, L.E. FEDOTOVA
Moscow Institute of Physics and Technology, Dolgoprudny. Russia; Ivanovo State Medical Academy of the RF Ministry of Health, Ivanovo, Russia

Summary:
Objective. To compare mexidol with control molecules (choline alfoscerate, piracetam, glycine, semax) using chemoreactome analysis. Material and methods. The chemical structure of mexidol was compared to molecule metabolites extracted from the Human Metabolome Database (HMDB) and a drug database. More than 40 000 of metabolites from HMDB were used as a model of human metabolome. Results and conclusion. The chemoreactome analysis showed that mexidol may be (1) an agonist of acetylcholine and GABA-A receptors; (2) an anti-inflammatory agent, the effects of which are carried out by inhibiting the synthesis of pro-inflammatory prostaglandins; (3) a neurotrophic agent with neuroprotective properties; (4) a coagulation inhibitor; (5) a diabetes medication and (6) a hypolipidemic agent. Compared to «control» molecules, mexidol has a more pronounced safety profile (a lower impact on serotonin, dopamine and adrenergic receptors, a lesser degree of interaction with the potassium channels of the heart, MAO and P450 cytochromes). The results of modeling allow to specify the mechanisms of action of mexidol at the molecular level.

Keywords: mexidol, neuroprotection, chemoreactome analysis, chemoinformatics, forecasting.

Mexidol effect on the factor induced by hypoxia HIF-1α expression in the rat cerebral cortex in its ischemia

Author:
E.N. YAKUSHEVA, P.YU. MYLNIKOV, I.V. CHERNYKH, A.V. SHCHULKIN.
Pavlov Ryazan State Medical University, Ryazan, Russia.

Summary:
The aim of the research – to study the Mexidol (ethylmethylhydroxypyridine succinate) effect on the factor induced by hypoxia (HIF-1α) expression in the frontal cortex of the brain in its ischemia. Material and methods. The work was performed on the 64 male Wistar rats. The expression of HIF-1α was determined immunohistochemically. Results and discussion. It is determined that single intraperitoneal administration of Mexidol at a dose 120 mg/kg and oral administration at a dose 100 mg/kg three times a day for 14 days is not affected the expression of HIF-1α. Unilateral occlusion of the common carotid artery increases the expression of HIF-1α at 4 hours after the occlusion. Oral administration of Mexidol at a dose 100 mg/kg three times a day for 14 days before and after ischemia increases the expression of HIF-1α after 4 and 12 hours in comparison with the norm, on the 5th day in comparison with occlusion control. Thus, it has been established that Mexidol increases the expression of HIF-1α in the frontal cortex of rat brain not under normal conditions, but in unilateral occlusion of the common carotid artery.

Keywords: mexidol, ethylmethylhydroxypyridine succinate, ischemia, occlusion of common carotid artery.

A comparative study of the effects of mexidolum and mildronatum on the physical performance of experimental animals

Author:
Т.А. VORONINA, I.G. KAPITSA, Е.А. IVANOVA.
Zakusov Institute of Pharmacology, Moscow, Russia.

Summary:
Objective. To evaluate the effects of mexidolum on physical performance using acute and subchronic administration in experimental animals. Materials and methods. The investigation was carried out using 123 male white outbred mice. The forced swim test was used to assess the effects of the drugs on the physical performance of mice. Results and conclusion. A single intraperitoneal administration of 50 and 100 mg/kg mexidolum and subchronic intraperitoneal administration of 100 mg/kg mexidolum significantly enhances the physical performance of animals in the forced swim test. Subchronic intraperitoneal administration of 100 mg/kg of the comparison drug mildronatum enhances the physical performance of animals, while intraperitoneal administration at a lower dose (50 mg/kg) has no effect. The effect of mexidolum at a dose of 50 and 100 mg/kg is comparable with the effect of mildronatum in a dose of 100 mg/kg.

Keywords: physical performance, mexidolum, mildronatum, mice.

The distribution of mexidol in the rat’s brain and its subcellular fractions

Author:
A.V. SHCHULKIN, E.N. YAKUSHEVA, I.V. CHERNYKH.
Pavlov Ryazan State Medical University, Ryazan.

Summary:
Objective: To study the penetration of mexidol through the blood-brain barrier into different brain compartments and cell mitochondria. Material and methods. The study was carried out on adult male Wistar rats using the drug mexidol (“Farmasoft” Russia). The penetration of mexidol into different compartments of the brain (the cortex, cerebellum, thalamus and medulla) and distribution between mitochondrial and cytoplasmic fractions of the cerebral cortex was studied. The concentration of mexidol in blood plasma and brain tissues was measured using HPLC. Results and Conclusion. Mexidol penetrated through the blood-brain barrier into brain compartments of rats with the maximal accumulation in the cortex. In the brain cortex cells, mexidol was identified in the cytoplasmic and mitochondrial fractions.

Keywords: mexidol, pharmacokinetics, blood-brain barrier, cortex, cerebellum, thalamus, medulla, mitochondria, HPLC.

Effect of mexidol on the development of the phenomenon of the neuronal excitotoxicity in vitro

Author:
A.V. SHCHULKIN.

Summary:
Effect of mexidol on the development of the phenomenon of the excitotoxic syndrome in vitro has been studied. Mexidol inhibits in vitro the development of glutamate-induced neurotoxicity, ascorbate-dependent (non-enzymatic) and NADPH2-dependent (enzymatic) iron-induced lipid peroxide oxidation, is able in high concentrations to bind superoxide anion-radical, significantly increases the activity of Se-dependent glutathione peroxidase, decreases the activity of induced NO-synthase and does not impact on the activity of glutathione-SH-transferase, catalase and neuronal NO-synthase. These effects underlie the antioxidant and antihypoxic action of the drug.

Keywords: mexidol, glutamate-induced neurotoxicity, lipid peroxide oxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione-SH-transferase, induced and neuronal NO-synthase.