[The effect of ethylmethylhydroxypyridine succinate on the parameters of chronic neuroinflammation and plastic processes in the brain of old rats during course of dexamethasone administration]. / Vliyanie etilmetilgidroksipiridina suktsinata na parametry khronicheskogo neirovospaleniya i plasticheskikh protsessov v mozge starykh krys pri kursovom vvedenii deksametazona.

OBJECTIVE: To study was to evaluate the potential modulatory impact of succinate/SUCNR1 signaling on the non-genomic immunosuppressive and gene-mediated inflammatory-degenerative effects of glucocorticoid receptor (GR) activation in the cerebral cortex (CC) of aging rats. MATERIAL AND METHODS: Using Western blot analysis, we assessed the expression level of pro-inflammatory (TNF-α, IL-1ß), anti-inflammatory cytokines (IL-10, TGF-ß1), mitochondriogenesis markers (PGC-1α, NDUFV2, SDHA, cyt c1, COX2, ATP5A), angiogenesis marker VEGF, neurotrophin BDNF, GR, succinate receptor SUCNR1 in the CC of 18-month-old rats with isolated administration of the highly specific GR ligand dexamethasone (1 mg/kg, i.p., daily, 10 days) and its combined administration with the succinate-containing drug Mexidol (100 mg/kg, i.p., daily, 10 days). RESULTS: Dexamethasone caused a decrease in the content of all detectable parameters in the CC of 18-month-old rats, including anti-inflammatory IL-10, TGF-ß1, PGC-1α, VEGF, BDNF, which progressed by 10 days, amounting to 40-60%, which is consistent with the literature data on transrepression by GR of key pro-inflammatory (NFkB, AP1, STAT1), anti-inflammatory (PPARγ, ERRα), pro-anabolic transcription factors (estrogen, androgen receptors). The administration of Mexidol daily an hour after the injection of dexamethasone did not affect the dexamethasone-induced suppression of pro-inflammatory cytokines, but increased the expression levels of anti-inflammatory cytokines, protein markers of mitochondrio-, angio- and synaptogenesis. CONCLUSION: The study demonstrates for the first time the prospect and pathogenetic foundation of the combined use of dexamethasone and Mexidol in an aging body in order to minimize the activity of GC aimed at suppressing pro-anabolic programs and mechanisms for resolving inflammation.

[The role of mitochondrial dysfunction in the stabilization of the glaucomatous process]. / Znachenie mitokhondrial'noi disfunktsii v stabilizatsii glaukomnogo protsessa.

Many key aspects of retinal ganglion cell (RGC) neurodegeneration in glaucoma are associated with mitochondrial dysfunction. Understanding the mechanisms and relationships between structural and functional changes in mitochondria would be beneficial for developing mitochondria-targeted therapeutic strategies to protect RGCs from glaucomatous neurodegeneration. PURPOSE: This study determines the extent of mitochondrial dysfunction in patients with primary open-angle glaucoma (POAG) and evaluates the potential for stabilizing the glaucomatous process by improving mitochondrial functional activity and energy production by therapy with Mexidol and Mexidol FORTE 250. MATERIAL AND METHODS: The study included 80 patients with moderate POAG with compensated intraocular pressure and 20 healthy volunteers. The extent of mitochondrial dysfunction was assessed by measuring the activity levels of mitochondrial enzymes: succinate dehydrogenase (SDH) and α-glycerophosphate dehydrogenase (α-GPDH) in peripheral blood lymphocytes using cytochemical analysis and cytometric morphology and density analysis (cytomorphodensitometry). Patients in the main group received sequential therapy with Mexidol as follows: Mexidol solution for intravenous and intramuscular administration at 50 mg/ml, 300 mg daily intramuscularly for 14 days, followed by Mexidol FORTE 250 tablets, one tablet three times daily for 56 days. Stabilization of glaucomatous optic neuropathy during treatment was evaluated using a comprehensive set of perimetric, electrophysiological, and structural-topographical methods at 14, 56, and 90 days. RESULTS: Sequential therapy in the main group resulted in a significant increase in mitochondrial enzyme activity at 14 and 56 days compared to baseline, with a gradual regression by the end of the observation period (90 days). This was accompanied by an increase in the number of mitochondria and an increase in their optical density as measured by cytomorphodensitometry. The improvement in mitochondrial enzyme activity at 14 and 56 days was associated with positive changes in the structural and functional parameters of the retina, as evidenced by static perimetry, optical coherence tomography, and a series of electrophysiological tests. CONCLUSION: The obtained data can be used to optimize POAG therapy by reducing mitochondrial dysfunction and stabilizing glaucomatous optic neuropathy.

The Study of the Effectiveness of Ethylmethylhydroxypyridine Succinate in Acute Alcohol Intoxication.

The effectiveness of ethylmethylhydroxypyridine succinate (EMHPS) in acute alcohol intoxication was tested in a study on SPF male outbred ICR mice. Ethanol (concentration 40%) was administered to animals once intraperitoneally at a dose of 4 g/kg. Control animals were injected with saline in an equivalent volume. In 15 min after the administration of alcohol, the animals were injected intravenously or intramuscularly with EMHPS at a dose of 50 or 100 mg/kg or with saline via the same route in an equivalent volume. Animal behavior was tested 3 and 24 h later after administration of the substances. After 3 and 24 h, mice in the pathological control groups developed semiptosis, the gait and the turning over reflex were impaired, the strength of the hind limbs decreased and the distance between the hind limbs increased when landing; in the open-field test, the latency of the first movement increased, and the number of rearing postures decreased. Intravenous and intramuscular administration of EMHPS in doses of 50 and 100 mg/kg had a pronounced antitoxic and neuroprotective effect in acute alcohol intoxication: all studied parameters did not differ significantly from the control.

[Cognitive impairment in patients with arterial hypertension]. / Kognitivnye narusheniya u patsientov s arterial'noi gipertenziei.

Arterial hypertension (AH) is a leading risk factor for cardiovascular diseases including cerebrovascular complications. Strokes and/or vascular cognitive impairment (VCI) are considered as a clinical sign of brain damage as a target organ in hypertension. To identify and assess the severity of VCI, patients with hypertension should undergo a neuropsychological assessment. Neuroimaging confirm the vascular origin of cognitive impairment. Patient management should include antihypertensive therapy along with neuroprotection. Among different neuroprotective therapy, ethylmethylhydroxypyridine succinate (mexidol) is one of medication with serious evidence of clinical efficacy.

[Results of a cohort single-center randomized study of the modulating effect of the drug Mexidol in the rehabilitation of patients who suffered acute cerebral insufficiency]. / Rezul'taty kogortnogo odnotsentrovogo randomizirovannogo issledovaniya moduliruyushchego effekta preparata Meksidol v reabilitatsii patsientov, perenesshikh ostruyu tserebral'nuyu nedostatochnost'.

OBJECTIVE: Evaluation of the effect of pharmacological modulation of the rehabilitation process with the drug mexidol as an adjuvant component of the rehabilitation treatment of cognitive-emotional disorders in patients who have suffered acute cerebral insufficiency (ACI) due to acute cerebrovascular accident or traumatic brain injury. MATERIAL AND METHODS: The study was conducted as a randomized interventional prospective study and consisted of 5 visits. Patients were divided into 2 groups: main (n=30, standard therapy + Mexidol IV 500 mg per day for 10 days, followed by Mexidol FORTE 250 orally, 1 tablet 3 times a day for 8 weeks) and control (n=30, standard therapy for 66 days). RESULTS: The study randomized 60 patients who underwent ACN and received rehabilitation treatment in accordance with regional routing. In the main group, there was an improvement in cognitive functions comparable to the control group (p<0.001, in both groups there was an improvement in the Schulte test «work efficiency¼ and «total execution time¼, according to the MoCA scale (visit 5 - 23.8±2.6 vs 22.9±31, p=0.227). A significant superiority of the main group over the control group was shown in such indicators as a decrease in anxiety (according to the HADS scale) (visit 4 - 2.6±2.4 vs 4.4±2.4, p=0.004), a decrease in the severity of depression (according to the Beck scale) (visit 3 - 7.5±4.5 vs 11.4±5.6, p=0.005). There was a tendency for the main group to be superior in terms of muscle strength (according to the MRC scale (visit 4 - 3.3±5.1 vs 2.1±2.2, p=0.051), level of vital activity (according to the ShRM - visit 5 - 2.9±0.7 vs 3.3±0.6, p=0.053). A statistically significant increase in the level of mobility of patients in the group using the drug Mexidol was proven compared to the control group (the difference in the Rivermead index at the 5th visit was 10.3±2.8 and 8.0±2.8, respectively, p=0.006), the average increase in the Rivermead index by visit 5 (5.4±2.1 vs 3.4±1.6, p<0.001). A decrease in intensive care aftereffects syndrome (ITS) scores was detected in both groups; a statistically significant decrease in the severity of ITS in relation to the previous visit was detected only in the group using the drug Mexidol (p<0.001). In the main group, the best indicators of the dynamics of systolic cerebral blood flow velocity and overshoot coefficient were also determined, compared to the control group. There were no adverse events recorded in the study. CONCLUSION: A positive modulating effect of Mexidol has been demonstrated in terms of accelerating the restoration of tolerance to cognitive loads, improving the psycho-emotional background by reducing symptoms of anxiety and depression, and secondary improving the results of motor rehabilitation in the early recovery period in patients who have undergone ACI, including those with manifestations of PIT syndrome. During the study, no adverse events were recorded, as well as significant differences in vital functions in the study groups, which indicates comparable safety of therapy in the control and main groups.

Characteristics of HIF-1Α and HSP70 MRNA Expression, Level, and Interleukins in Experimental Chronic Generalized Periodontitis.

OBJECTIVES: Periodontal diseases are a rather complex problem of modern dentistry and do not have only medical but also social significance. The objective of this study is to weigh the effect of a mixture of Thiotriazoline and L-arginine (1:4) on the parameters of the system of endogenous cytoprotection of blood and periodontal illness in rats with experimental chronic generalized periodontitis and substantiate further study of this blend. MATERIALS AND METHODS: The study aimed to evaluate the impact of a combination of Thiotriazoline and L-arginine (in a ratio of 1:4) on the parameters of the endogenous blood cytoprotection system and periodontium in rats with experimental chronic generalized periodontitis. A group of outbred rats weighing 190-220 g and sourced from the vivarium of the Institute of Pharmacology and Toxicology of the Academy of Medical Sciences of Ukraine were divided into four groups, each consisting of 10 animals. (1) Intact group, animals that were injected intragastrically with a solution of sodium chloride to chloride 0.9% for 30 days. (2) control, animals with experimental CGP who intragastrically sodium chloride solution 0.9% for 30 days. (3) animals with experimental CGP were injected intramuscularly with Thiotriazoline + L-arginine (1:4) in a dosage of 200 mg/kg (30 days). (4) animals with experimental CGP, for which daily intragastric reference drug Mexidol, in dosage 250 mg/kg (30 days). In this study, we utilized two substances: Thiotriazoline and L-arginine hydrochloride. The combination of Thiotriazoline and L-arginine (in a ratio of 1:4) was prepared at the Department of Pharmaceutical Chemistry of ZSMU. At the conclusion of the experiment, the rats were carefully removed from the study while under thiopental-sodium anesthesia, and administered at a dosage of 40 mg/kg. RESULTS: We have found that the administration of a combined preparation of Thiotriazoline with L-arginine to rats with CGP leads to a significant decrease in the blood concentration of pro-inflammatory cytokines IL-1b and TNF-a by 56.1% and 71%, respectively. CONCLUSION: The administration of Mexidol at a dosage of 250 mg/kg, as well as the combination of Thiotriazoline and Larginine in a ratio of 1:4 at a dosage of 200 mg/kg, resulted in a significant reduction in gingival pocket depth in animals with CGP. Specifically, the gingival pocket depth was reduced to 6 mm (p < 0.05) with Mexidol and further reduced to 4 mm (p < 0.05) with the combination of Thiotriazoline and L-arginine. Additionally, the animals exhibited minimal bleeding, swelling, and tooth mobility when treated with the combination of Thiotriazoline and L-arginine. The administration of a combination of Thiotriazoline and L-arginine (in a ratio of 1:4) at a dosage of 200 mg/kg to animals with CGP resulted in a noteworthy reduction in the blood concentration of pro-inflammatory cytokines IL-1b and TNF-a. Specifically, there was a significant decrease of 56.1% (p < 0.05) in IL-1b and 71% (p < 0.05) in TNF-a levels. The course administration of a combination of Thiotriazoline and L-arginine (1:4) (200 mg/kg) to animals with CGP led to an increased expression of HSP70 mRNA (p < 0.05) in the periodontium by 8.2 times and HIF-1a mRNA by 8.2 times. 2.8 times (p < 0.05) against the background of an increase in the blood concentration of HSP70 by 95% (p < 0.05). Also, in the periodontium of animals in this group, a decrease in the expression of c-Fos mRNA by 36.7% (p < 0.05) was found compared to the control group.

[Efficacy of Mexidol in combination with cerebral revascularization in the treatment of ischemic stroke]. / Effektivnost' primeneniya Meksidola v kombinatsii s revaskulyarizatsiei golovnogo mozga v terapii ishemicheskogo insul'ta.

Stroke is an acute life-threatening condition; its outcome is determined by the degree of damage to brain tissue, the quality and speed of medical care in the first minutes and hours after its occurrence. The main mechanism of brain tissue damage during both ischemia and reperfusion is oxidative stress. The review covers adverse influence oxidative stress at the cerebral ischemia and reperfusion periodes of ischemic stroke. The results of preclinical studies demonstrating the ability of Mexidol to neutralize the effects of free radicals and activate antioxidant protection are presented. Data from clinical studies of the use of Mexidol in combination with thrombolysis in patients with ischemic stroke are reviewed.

[Neurometabolic therapy of mild cognitive impairment in patients with chronic cerebral ischemia]. / Neirometabolicheskaya terapiya umerennykh kognitivnykh rasstroistv u patsientov s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To evaluate the effect of a sequential therapy regimen with Mexidol (500 mg injections intravenously for 14 days) and Mexidol FORTE 250 (250 mg tablets 3 times a day for 60 days) on higher cortical functions in patients with moderate cognitive disorders in chronic cerebral ischemia. MATERIAL AND METHODS: A comparative, prospective study included 63 patients with chronic cerebral ischemia with moderate cognitive impairment. All patients received basic therapy aimed at reducing risk factors (antihypertensive, antithrombotic drugs as indicated). Patients of the main group (30 people: 12 men, 18 women) received Mexidol intravenously 500 mg in 100 ml of 0.9% NaCl solution once a day for 14 days, then Mexidol FORTE 250 (film-coated tablets) 250 mg 3 times a day for the next 60 days. The comparison group consisted of 33 patients (14 men, 19 women) who received only basic therapy. The groups were comparable in terms of age, sex characteristics and severity of cognitive deficit. We examined cognitive status (MoCA scale, Frontal Dysfunction Battery, 10 Word Memorization tests), severity of asthenia (MFI-20 scale), anxiety and depression (HADS scale), patient's subjective assessment of the dynamics of the condition (CGI-improvement scale) in 1st, 14th and 74th±5 days of observation. On days 1 and 74±5 of observation, patients were examined using transcranial magnetic stimulation to study the neuronal activity of the cerebral cortex. RESULTS: In the main group, at the time of completion of taking Mexidol and Mexidol FORTE 250, a pronounced cognitive regression was noted (MoCA scale +3 points, difference with the comparison group 1 point (p<0.0001); Frontal Dysfunction Battery test +4 points, difference with comparison group 2 points (p<0.001); memory test «10 words¼ +2 points, difference with the comparison group 1 point (p<0.05), emotional (HADS anxiety scale -8 points, difference with the comparison group 3 points (p<0.001), depression -3.5 points, difference with the comparison group 1.5 points (p<0.01), asthenic disorders (MFI-20 scale -30 points, difference with the comparison group 15.5 points (p<0.01), improvement in the well-being of patients (CGI-improvement scale -2 points, difference with the comparison group 1 point (p<0.0001). According to the transcranial magnetic stimulation performed, a statistically significant decrease in the central motor conduction time at the level of 1 and 2 motor neurons of the pyramidal tract bilaterally from the start to the end of therapy with Mexidol and Mexidol FORTE 250 was determined (p<0.01). An inverse correlation was found between the time of central motor conduction and the results of the Frontal Dysfunction Battery test at the same time points with left-sided localization of 1 motor neuron (p<0.01). The results of a study of the use of sequential therapy with Mexidol 500 mg IV drip 1 time per day for 14 days followed by oral administration of Mexidol FORTE 250 1 tablet 3 times a day for 60 days indicate its clinical effectiveness and safety in patients with chronic cerebral ischemia with mild cognitive impairment, and also confirm its importance for preventing the progression of cognitive disorders.

[Treatment of patients with ishemic stroke in the vertebral-basilar system in acute period: experience of using the neuroprotective drug Mexidol]. / Lechenie bol'nykh ishemicheskim insul'tom v vertebral'no-bazilyarnoi sisteme v ostrom periode: opyt primeneniya neiroprotektivnogo preparata Meksidol.

OBJECTIVE: To assess the clinical efficacy and safety of Mexidol in patients in acute period of ishemic stroke in the vertebral-basilar system (iiVBS). MATERIAL AND METHODS: An open randomized comparative study involved 52 patients. 32 of them received Mexidol (mail group, MG) and 20 received therapy without neuroprotective drugs. Assessment of the severity of clinical manifestations of iiVBS was performed using the Hoffenberth scale, stroke severity was assessed using the NIHSS, the modified Rankin Scale was used to assess the degree of disability in patients after stroke, neuropsychological examination of patients was performed using the Montreal Cognitive Assessment (MoCA), dynamics were compared on the Hospital Anxiety and Depression Scale (HADS), Subjective assessment scale for asthenia (MFI-20), the patients' quality of life was assessed using the EQ-5D. RESULTS: The use of Mexidol in the form of long-term sequential therapy in the patients of the MG led to a 53.3% decrease in the severity of clinical manifestations of iiVBS and a 59.5% decrease in neurological deficit according to the NIHSS scale. By the end of Mexidol therapy, 96.9% of patients MG were able to manage their own affairs without assistance (modified Rankin Scale), which was accompanied by regression of emotional disturbances and improved quality of life of patients. CONCLUSION: Administration of Mexidol in therapy of patients with acute iiVBS can be considered the most justified, since it contributes to an earlier and more significant reduction of neurological deficit and improvement of patients' quality of life.

Mexidol, Cytoflavin, and succinic acid derivatives as antihypoxic, anti-ischemic metabolic modulators, and ergogenic aids in athletes and consideration of their potential as performance enhancing drugs.

Emoxypine (ethylmethylhydroxypyridine) is a synthetic derivative of vitamin B6 . Emoxypine succinate is a registered drug in Russia and Ukraine under various trade names including Mexidol, Mexicor, and Armadin Long. Mexidol demonstrates antihypoxic and anti-ischemic effects and also modulates metabolism. The use of Mexidol by Russian athletes has been confirmed in the past. Current use by athletes is unknown as this drug is not monitored or included in drug testing protocol. Metabotropic and antihypoxic effects of Mexidol were compared to the effects of meldonium or trimetazidine, both of which are included on the World Anti-Doping Agency (WADA) Prohibited List in category S4.4. Metabolic Modulators. The conjugation of emoxypine with succinate elevates the therapeutic effectiveness of the Mexidol formulation as succinic acid itself has important impacts to consider despite being a common food additive and drug excipient. Other succinic acid salts like ammonium succinate, found as dietary supplement, have been patented as performance enhancers. Available research on healthy subjects suggests that combinations of selected 3-substituted pyridine derivatives with succinate including Mexidol and a related drug Cytoflavin can enhance the performance of athletes. Cytoflavin is a multi-component formula containing meglumine sodium succinate, nicotinamide (vitamin B3 ), inosine (riboxin), and riboflavin. Other related succinate-based drugs include Remaxol, Reamberin, and Cogitum. Mexidol and Cytoflavin and related substances exhibit similar biological effects as drugs on the WADA Prohibited List, and if they are used for performance enhancement by athletes, they could be worthy of consideration as prohibited substances in sport.

[The use of Mexidol in patients with mild (moderate) cognitive impairment: results of a meta-analysis]. / Primenenie Meksidola u patsientov s legkimi (umerennymi) kognitivnymi narusheniyami: rezul'taty metaanaliza.

OBJECTIVE: To conduct a meta-analysis of the effectiveness of Mexidol therapy in patients with chronic brain ischemia (CBI) and cognitive disorders (CD). MATERIAL AND METHODS: This meta-analysis included the results of studies on the effectiveness of Mexidol in patients with CD measured with Montreal Cognitive Assessment Scale (MoCA). The pooled effect assessment included all publications from independent clinical trials that provided efficacy data on the MoCA scale with a level of detail sufficient for further mathematical analysis. The main result of the meta-analysis was obtained for the final values of the effectiveness indicator in the Mexidol groups compared with the basic therapy groups. Data from 10 prospective randomized trials containing information on the final scores on the MoCA scale after therapy was analyzed. RESULTS: The meta-analysis of ten prospective clinical studies of the effectiveness of Mexidol against the background of basic therapy in patients with CCI and CD was carried out. The total number of patients taking Mexidol was 482; the comparison group consisted of 455 patients. According to the results of a statistical model of random effects, the effect size was 2.06; 95% confidence interval for the difference in effectiveness between the groups of the study drug and the control groups [0.98; 3.14] (p=0.0002). CONCLUSION: A statistically significant and clinically significant improvement in the cognitive functions of patients with CBI, was demonstrated after treatment with Mexidol.

[The impact of therapy with Mexidol on neurological deficit and functional outcome in patients with ischemic stroke: a systematic review and meta-analysis]. / Vliyanie terapii preparatom Meksidol na regress nevrologicheskogo defitsita i funktsional'nyi iskhod u patsientov s ishemicheskim insul'tom: sistematizirovannyi obzor i metaanaliz.

OBJECTIVE: To evaluate systematically the published peer-reviewed literature and estimate the effect of therapy with Mexidol on the course and outcomes of ischemic stroke (II) in adult patients. MATERIAL AND METHODS: The meta-analysis included 11 studies reported In Russian (2 randomized controlled studies, 9 non-randomized, unblinded cohort studies). RESULTS: The results obtained indicate a positive effect of Mexidol on the course of II in the treated adult patients: we found statistically significant decrease in NIHSS scores on days 7-10 and 21-24 and in modified Rankin scale scores on days 5-7 and days 10-14 compared with the control group. The cumulative effect of the drug was shown: the between-group difference of the NIHSS scores increases with the course of observation time. The effect of Mexidol on indicators on the NIHSS scale is more significant, the greater the initial severity of the patient's neurological deficit. CONCLUSION: Heterogeneity in study designs and patient characteristics has resulted in significant statistical heterogeneity, and the evidence presented at the time of writing requires further examination as new data become available.

[An effect of ethylmethylhydroxypyridine succinate and ethylmethylhydroxypyridine malate on changes in mitochondrial function under conditions of focal cerebral ischemia]. / Vliyanie etilmetilgidroksipiridina suktsinata i etilmetilgidroksipiridina malata na izmenenie mitokhondrial'noi funktsii v usloviyakh fokal'noi ishemii golovnogo mozga.

OBJECTIVE: To evaluate an effect of ethylmethylhydroxypyridine succinate and ethylmethylhydroxypyridine malate on changes in mitochondrial function under experimental focal cerebral ischemia. MATERIAL AND METHODS: Focal cerebral ischemia was modeled in Wistar rats by thermocoagulation of the middle cerebral artery. Ethylmethylhydroxypyridine succinate («Mexidol¼) and ethylmethylhydroxypyridine malate («Ethoxidol¼) were injected into the tail vein 30 minutes after ischemia simulation and then for 3 days at doses of 50 mg/kg, 100 mg/kg and 150 mg/kg. After 72 hours, changes in neurological deficits, aerobic and anaerobic respiration activity, the concentration of mitochondrial hydrogen peroxide and apoptosis-inducing factor, as well as the activity of succinate dehydrogenase and cytochrome c oxidase in brain tissue supernatants were assessed. RESULTS: The course administration of ethylmethylhydroxypyridine succinate and ethylmethylhydroxypyridine malate dose-dependently contributed to a decrease in the concentration of mitochondrial hydrogen peroxide and apoptosis-inducing factor in the brain tissue. The restoration of mitochondrial energy function was also shown with the use of ethylmethylhydroxypyridine succinate in all studied doses, while the administration of ethylmethylhydroxypyridine malate led to the restoration of mitochondrial-dependent energy production only at higher doses (100 mg/kg and 150 mg/kg). CONCLUSION: The effect of malic acid and succinic acid salts of ethylmethylhydroxypyridine on the change in the redox and apoptosis-regulating function of mitochondria does not depend on the type of anion, whereas the change in the energy function of mitochondria is associated with the salt residue included in the drug structure and its dosage.

[The possibilities of Mexidol usage in neuropediatrics]. / Vozmozhnosti primeneniya Meksidola v neiropediatrii.

Mexidol (ethylmethylhydroxypyridine succinate) is a modern neurometabolic medication increasingly being used in neuropediatrics. The results of recent studies confirming the positive effects of Mexidol pharmacotherapy in children with attention deficit hyperactivity disorder (ADHD), perinatal damages of the central nervous system (hypoxic-ischemic encephalopathy) and their consequences, neurological disorders and neurodevelopmental delay after surgery for congenital heart defects, neuroinfections (meningitis, encephalitis), posttraumatic epilepsy. Taking into account the unique multimodal action of Mexidol, it seems promising to expand the range of indications for its application in neuropediatrics, based on the results of new clinical trials organized in accordance with modern principles of evidence-based medicine.

[Pharmacotherapy approaches to vascular mild cognitive impairment in patients of different age groups]. / Podkhody k farmakoterapii sosudistykh umerennykh kognitivnykh narushenii u patsientov razlichnykh vozrastnykh grupp.

The article discusses the possibilities of pharmacotherapy of moderate vascular cognitive impairment in different age groups. The results of a double-blind randomized clinical trial «MEMO¼ using the antioxidant and antihypoxic drug Mexidol are presented. On the basis of cognitive scales, when using a sequential course of parenteral and oral administration of mexidol, its reliable effectiveness was shown in each of the three analyzed groups: 40-60 years old, 61-75 years old and 76-90 years old. Mexidol showed an optimal safety profile in all age groups.

[Features of pharmacotherapy of vascular cognitive impairment in the elderly]. / Osobennosti farmakoterapii sosudistykh kognitivnykh narushenii u lits pozhilogo vozrasta.

The problem of pharmacotherapy of elderly and senile people is currently extremely relevant due to the aging of the population and the increase in the prevalence of cardiovascular diseases. One of the most serious problems of the elderly is the development of cognitive decline due to cerebrovascular pathology. However, elderly patients often have a large number of comorbid diseases, which leads to difficulties in diagnosing and managing these patients, and often to the development of polypharmacy, which can lead to deterioration in functional status, cognitive impairment, adverse reactions and drug interactions. In addition, in elderly patients, there may be changes in pharmacokinetics and pharmacodynamics due to anatomical and physiological involutive processes. At the same time, the number of drugs whose clinical efficacy and tolerability were evaluated specifically in elderly and senile patients is relatively small. In a randomized clinical trial of sequential parenteral and oral therapy with Mexidol in patients with mild vascular cognitive impairment syndrome, a positive effect of this therapy on various domains (cognitive, emotional, autonomic, motor) of chronic cerebrovascular disease was confirmed compared with placebo, which allows us to recommend it for use in elderly and senile patients.

[The effect of antioxidant therapy on some pathogenetic factors of primary open-angle glaucoma]. / Vliyanie antioksidantnoi terapii na nekotorye patogeneticheskie faktory pervichnoi otkrytougol'noi glaukomy.

In patients with glaucoma, one of the main initiating mechanisms that triggers the chain of events is disruption of the universal mechanism for regulating vascular tone due to endothelial dysfunction (ED). The main manifestation of ED is an imbalance of vasoconstrictor and vasodilator endothelial mediators, which inconsistency triggers the mechanisms of adaptive distress leading to the progression of morphological destruction, dyslipidemia, acceleration of atherogenesis, development of hemodynamic and hydrodynamic disorders. The drug Mexidol has a wide range of pharmacological activity and affects the main pathogenetic links of primary open-angle glaucoma (POAG). PURPOSE: The study analyzes the vascular remodulation, antioxidant and antihypoxic effects of the drug Mexidol in patients with PAOG. MATERIAL AND METHODS: The study included 78 patients with POAG of the early (n=43) and advanced stage (n=35) with average age of 67.8±1.5 years. The main study group consisted of 47 patients who received Mexidol in addition to local hypotensive treatment; 31 patients comprised the control group. In the comparison groups, the degree of ED was determined by the results of reactive hyperemia test, patients' blood plasma was analyzed for levels of stable nitric oxide metabolite (nitrite NO2-) and endothelin-1 (ET-1). General assessment of oxidative stress was carried out by high-performance liquid chromatography. Functional activity of the retina was studied using an electroretinograph and static computer perimetry performed according to the standard technique. RESULTS: The following changes are observed in patients of the main group using Mexidol: the index of oscillatory potentials significantly increases, peak latency decreases, perimeter indices show positive trends, vascular endothelial function improves according to reactive hyperemia test, concentration of vasoconstrictor mediator ET-1 in blood plasma decreases and of nitrite (NO2-) increases moderately, the coefficient of bioeffective vasotonic activity decreases, the level of glutathione peroxidase increases (p<0.05 compared to the baseline value), the level of malonyldialdehyde decreases, lipid metabolism improves (reduction in total cholesterol, low-density lipoprotein-cholesterol, triglycerides, decrease in the Atherogenic Index compared to the initial level). CONCLUSIONS: The drug Mexidol proved to be an effective endothelial protector, a powerful antioxidant and antihypoxant, contributed to deceleration of atherogenesis in patients with POAG.

[Efficacy of Mexidol in the correction of postcovid syndrome in patients with chronic cerebrovascular diseases]. / Effektivnost' preparata Meksidol v korrektsii postkovidnogo sindroma u patsientov s khronicheskimi tserebrovaskulyarnymi zabolevaniyami.

OBJECTIVE: To evaluate the effectiveness of sequential therapy with Mexidol and Mexidol FORTE 250 in the correction of postcovoid syndrome (PKS) in patients with chronic cerebrovascular diseases (CVD). MATERIAL AND METHODS: The analysis of the results of examination and treatment of 110 patients with CVD who underwent COVID-19 was carried out. Patients of the main group (OH, n=55) received Mexidol (5 ml IV drip for 14 days, followed by the transition to the tablet form of Mexidol FORTE 250 1 table 3 times/day for 2 months); 55 patients of the comparison group (GS) did not receive antioxidants. All patients included in the study were conducted MRI examination and extensive neuropsychological testing. RESULTS: There was a significant improvement in the state of cognitive functions, regression of symptoms of asthenia, improvement of night sleep in patients with OG. The differences were statistically significant both in comparison with the baseline level and the HS. CONCLUSION: The administration of the drug does not require age-related dose adjustment and is well combined with basic therapy. The recommended regimen for the use of Mexidol: 14 days of 5 ml i/v or i/m, then taking the drug Mexidol FORTE 250 at a dose of 1 table 3 times/day for 2 months.

[Clinico-psychological profile and life quality of patients with post-COVID syndrome]. / Kliniko-psikhologicheskii profil' i kachestvo zhizni patsientov s postkovidnym sindromom.

OBJECTIVE: To study clinico-psychological profile and life quality of patients with post-COVID syndrome. MATERIAL AND METHODS: We examined 162 patients aged 24-60 years with confirmed SARS-CoV-2 infection which having symptoms that served as the basis for the diagnosis of post-COVID syndrome. Patients underwent general neurological and somatic examination with allocation of the corresponding neurological syndromes. The intensity and quality of pain were assessed using the McGill Pain questionnaire. The level of psychosocial stress was determined by the Holmes-Ray questionnaire, the identification and severity of asthenia - by the MFI-20 asthenia scale. The level of reactive and personal anxiety was studied according to the Spielberger-Khanin questionnaire, depression - according to the Beck scale. The assessment of life quality was carried out using the Russian version of SF-36 questionnaire. To correct the identified disorders, Mexidol was used according to the scheme: 500 mg once daily intravenously for 14 days, followed by Mexidol FORTE 250 750 mg per day orally (250 mg 3 times a day) for 2 months. RESULTS: The course of treatment with Mexidol in patients with post-COVID syndrome led to decrease in the severity of subjective and objective symptoms, asthenic, anxiety and depressive disorders, and improved the life quality of patients. CONCLUSION: The high efficacy and safety of sequential therapy with Mexidol (injections followed by tablets of Mexidol FORTE 250) has been shown.

[Features of treatment and rehabilitation of COVID-19 patients with ischemic stroke]. / Osobennosti lecheniya i reabilitatsiya bol'nykh, perenesshikh COVID-19, s ishemicheskim insul'tom.

The development of COVID-19 is associated with damage to various organs and organ systems, including the development of acute ischemic stroke (AI). The article examines modern ideas about the pathogenesis of AI in COVID-19. The data on the choice of optimal therapy for patients with acute AI and COVID-19, as well as on the possibility of improving the effectiveness of rehabilitation measures, are analyzed. Information is provided on the efficacy of the drug Mexidol in patients with AI and COVID-19.