[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.

A randomized prospective study comparing the effect of low-volume bowel preparations for colonoscopy preparation in China.

AIM: To evaluate the effect of sodium picosulfate/magnesium citrate (SPMC) and 3 L split-dose polyethylene glycol (PEG) with or without dimethicone on bowel preparation before colonoscopy. METHODS: In this multicenter, prospective, randomized, controlled study conducted from April 2021 to December 2021, consecutive adult patients scheduled for colonoscopy were prospectively randomized into four groups: SPMC, SPMC plus dimethicone, 3 L PEG, and 3 L PEG plus dimethicone. Primary endpoint was colon cleansing based on Boston Bowel Preparation Scale (BBPS). Secondary endpoints were bubble score, time to cecal intubation, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS: We enrolled 223 and 291 patients in SPMC and 3 L PEG group, respectively. The proportion with acceptable bowel cleansing, total BBPS score and cecal intubation time were similar in all four subgroups (p > 0.05). Patient-reported acceptability and tolerability was significantly greater in SPMC than 3 L PEG group (p < 0.001); adverse events were significantly lower in SPMC than latter group (p < 0.001). ADR in both groups was greater than 30%. CONCLUSION: SPMC had significantly higher acceptability and tolerability than 3 L PEG, however, was similar in terms of bowel-cleansing effect and cecal intubation time and hence can be used before colonoscopy preparation.

Efficacy and safety of same-day preparation with sodium picosulfate plus magnesium citrate on the day of colonoscopy for bowel preparation: Multicenter, single-arm, open-label study.

BACKGROUND AND AIM: Sodium picosulfate plus magnesium citrate (SP + MC) is a well-tolerated bowel preparation agent. However, Japan currently approves only two methods of taking SP + MC: the day-before and split-dose preparation, without approval of same-day preparations. This study aimed to evaluate the efficacy and safety of same-day SP + MC preparations. METHODS: This was a multicenter, single-arm, nonrandomized, open-label study. We enrolled 145 Japanese patients between June and December 2023. The patients received two sachets of SP + MC dissolved in 300 ml of water and 1200 mL or more of clear liquid on the day of colonoscopy. Bowel cleansing efficacy, adverse events (AEs), and patient satisfaction were evaluated. RESULTS: Of the enrolled patients, 137 underwent colonoscopy according to our protocol. Bowel preparation was adequate in 133 patients (97.1%). The mean total Boston Bowel Preparation Score was 8.3 ± 1.2. Five patients experienced AEs (3.6%): two (1.5%), abdominal pain; one (0.73%), ischemic enteritis; one (0.73%), vomiting or nausea; and one (0.73%), headache. All AEs were treated conservatively. None of the patients exhibited abnormal blood test results or clinical symptoms after receiving SP + MC. Regarding patient satisfaction, all patients were able to take SP + MC as directed; 136 (99.2%) expressed a preference for this bowel preparation for future colonoscopies. CONCLUSION: The same-day SP + MC preparation showed high bowel-cleansing efficacy and satisfaction in Japanese patients without serious AEs.

Superior bowel preparation quality for colonoscopy with 1L-PEG compared to 2L-PEG and picosulphate: Data from a large real-world retrospective outpatient cohort.

BACKGROUND: Several randomized clinical trials comparing different bowel preparations (BP) have shown similar efficacy; however, there is a lack of real-world studies on this topic. AIMS: This study aims to identify the most effective BP regimen in a real-world setting and any predictors of inadequate BP. METHODS: A retrospective single-center study was conducted over 14 months at an academic hospital including outpatient colonoscopies in which adult patients did not teach on how to perform BP before colonoscopy. Colonoscopies with 1L-PEG, 2L-PEG and picosulphate mixtures were considered. A multivariable analysis for factors associated to poor BP was fitted. RESULTS: Overall, 1779 patients (51 %F, 60±14) years were included. The 1L-PEG regimen provided a higher rate of BP adequacy at multivariate analysis (adjusted OR 2.30, 95 %CI 1.67-3.16,p < 0.001) and was associated with higher median Boston Bowel Preparation Scale score (p < 0.001), higher rate of right-colon cleansing (p < 0.001) and exam completion (p = 0.04). Furthermore, we identified male sex, history of constipation, active smoking, previous pelvic surgery, concomitant psychiatric/neurological or chronic kidney diseases as predictors of inadequate BP. CONCLUSIONS: This is the largest real-world study comparing 1L-PEG to other BP regimens. Our results suggest 1L-PEG provides better BP in a non-controlled setting, improving clinical practice quality and minimizing the need for repeated colonoscopies and saving healthcare resources.

[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.

Gram-negative bacteria recognition and photodynamic elimination by Zn-DPA based sensitizers.

The abuse and overuse of antibiotics let drug-resistant bacteria emerges. Antibacterial photodynamic therapy (APDT) has shown outstanding merits to eliminate the drug-resistant bacteria via cytotoxic reactive oxygen species produced by irradiating photosensitizer. However, most of photosensitizers are not effective for Gram-negative bacteria elimination. Herein conjugates of NBS, a photosensitizer, linked with one (NBS-DPA-Zn) or two (NBS-2DPA-Zn) equivalents of zinc-dipicolylamine (Zn-DPA) have been designed to achieve the functional recognition of different bacteria. Due to the cationic character of NBS and metal transfer channel effect of Zn-DPA, NBS-DPA-Zn exhibited the first regent to distinguish P. aeruginosa from other Gram-negative bacteria. Whereas NBS-2DPA-Zn showed broad-spectrum antibacterial effect because the two arm of double Zn-DPA enhanced interactions with anionic membranes of bacteria, led the bacteria aggregation and thus provided the efficacy of APDT to bacteria and corresponding biofilm. In combination with a hydrogel of Pluronic, NBS-2DPA-Zn@gel shows promising clinical application in mixed bacterial diabetic mouse model infection. This might propose a new method that can realize functional identification and elimination of bacteria through intelligent regulation of Zn-DPA, and shows excellent potential for antibacterial application.

Crystal structure, intermolecular interactions, charge-density distribution and ADME properties of the acridinium 4-nitrobenzoate and 2-amino-3-methylpyridinium 4-nitrobenzoate salts: a combined experimental and theoretical study.

Acridines are a class of bioactive agents which exhibit high biological stability and the ability to intercalate with DNA; they have a wide range of applications. Pyridine derivatives have a wide range of biological activities. To enhance the properties of acridine and 2-amino-3-methylpyridine as the active pharmaceutical ingredient (API), 4-nitrobenzoic acid was chosen as a coformer. In the present study, a mixture of acridine and 4-nitrobenzoic acid forms the salt acridinium 4-nitrobenzoate, C13H10N+·C7H4NO4- (I), whereas a mixture of 2-amino-3-methylpyridine and 4-nitrobenzoic acid forms the salt 2-amino-3-methylpyridinium 4-nitrobenzoate, C6H9N2+·C7H4NO4- (II). In both salts, protonation takes place at the ring N atom. The crystal structure of both salts is predominantly governed by hydrogen-bond interactions. In salt I, C-H...O and N-H...O interactions form an infinite chain in the crystal, whereas in salt II, intermolecular N-H...O interactions form an eight-membered R22(8) ring motif. A theoretical charge-density analysis reveals the charge-density distribution of the inter- and intramolecular interactions of both salts. An in-silico ADME analysis predicts the druglikeness properties of both salts and the results confirm that both salts are potential drug candidates with good bioavailability scores and there is no violation of the Lipinski rules, which supports the druglikeness properties of both salts. However, although both salts exhibit drug-like properties, salt I has higher gastrointestinal absorption than salt II and hence it may be considered a potential drug candidate.

[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.

Organocatalyzed Amine-Free O-Phosphorylation of Alcohols with 4-Methylpyridine N-Oxide.

Amine-free phosphorylation of various alcohols was developed with 4-methylpyridine N-oxide in the presence of 4 Å molecular sieves at room temperature. This mild method gave various phosphorylated products in high yield and could be applied to acid- or base-sensitive substrates. Furthermore, this method was also effective for the chemoselective phosphorylation of diols or polyols.

[Possibilities of «therapeutic retargeting¼ of 3-hydroxypyridine and succinic acid derivatives due to their dopaminergic action]. / Vozmozhnosti «terapevticheskogo perenatselivaniya¼ proizvodnykh 3-oksipiridina i yantarnoi kisloty, obuslovlennye ikh dofaminergicheskim deistviem.

The review is devoted to a comparative analysis of the clinical efficacy of the original domestic derivatives of 3-hydroxypyridine and succinic acid (emoxipine, reamberin and mexidol) in comparison with the results of an experimental study of their dopaminergic action. The position that the dopaminomimetic activity of emoxipin, reamberin and mexidol largely determines their anti-ischemic, antihypoxic, insulin-potentiating neuroprotective, nootropic and antidepressant potential has been substantiated. A comparative analysis of the safety profile of emoxipine, reamberin and mexidol was carried out, taking into account potential and real side-effects caused by iatrogenic deviations from the eudopaminergic state. It has been shown that mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), which is simultaneously a derivative of 3-hydroxypyridine and succinic acid, has the best balance of efficacy and safety. A generalized assessment of the available data on the successful use of off-label derivatives of 3-hydroxypyridine and succinic acid indicates the advisability of a significant expansion of indications for their clinical use. The authors resume that the «therapeutic retargeting¼ of emoxipin, reamberin and mexidol (i.e. their use for qualitatively new indications) will contribute to progress in the treatment of socially significant and most common diseases.

[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.

The cytotoxic and antiproliferative properties of ruthenium nitrosyl complexes and their modulation effect on cytochrome P450 in the HepG2 cell line.

Ruthenium nitrosyl complexes are actively investigated as antitumor agents. Evaluation of potential interactions between cytochromes P450 (CYPs) with new compounds is carried out regularly during early drug development. In this study we have investigated the cytotoxic and antiproliferative activities of ruthenium nitrosyl complexes with methyl/ethyl esters of nicotinic and isonicotinic acids and γ-picoline against 2D and 3D cultures of human hepatocellular carcinoma HepG2 and non-cancer human lung fibroblasts MRC-5, assessed their photoinduced activity at λrad = 445 nm, and also evaluated their modulating effect on CYP3A4, CYP2C9, and CYP2C19. The study of cytotoxic and antiproliferative activities against 2D and 3D cell models was performed using phenotypic-based high content screening (HCS). The expression of CYP3A4, CYP2C9, and CYP2C19 mRNAs and CYP3A4 protein was examined using target-based HCS. The results of CYP3A4 mRNA expression were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). The ruthenium nitrosyl complexes exhibited a dose-dependent cytotoxic effect against HepG2 and MRC-5 cells. The cytotoxic activity of complexes with ethyl isonicotinate (1) and nicotinate (3, 4) was significantly lower for MRC-5 than for HepG2, for a complex with methyl isonicotinate (2) it was higher for MRC-5 than for HepG2, for a complex with γ-picoline (5) it was comparable for both lines. The antiproliferative effect of complexes 2 and 5 was one order of magnitude higher for MRC-5; for complexes 1, 3, and 4 it was comparable for both lines. The cytotoxic activity of all compounds for 3D HepG2 was lower than for 2D HepG2, with the exception of 4. Photoactivation affected the activity of complex 1 only. Its cytotoxic activity decreased, while the antiproliferative activity increased. The ruthenium nitrosyl complexes 1-4 acted as inducers of CYP3A4 and CYP2C19, while the complex with γ-picoline (5) induced of CYP3A4. Among the studied ruthenium nitrosyl complexes, the most promising potential antitumor compound is the ruthenium compound with methyl nicotinate (4).

[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.

Comparison of the efficacy and tolerability of elobixibat plus sodium picosulfate with magnesium citrate and split-dose 2-L polyethylene glycol with ascorbic acid for bowel preparation before outpatient colonoscopy: a study protocol for the multicentre, randomised, controlled E-PLUS trial.

BACKGROUND: Sodium picosulfate (SP)/magnesium citrate (MC) and polyethylene glycol (PEG) plus ascorbic acid are recommended by Western guidelines as laxative solutions for bowel preparation. Clinically, SP/MC has a slower post-dose defaecation response than PEG and is perceived as less cleansing; therefore, it is not currently used for major bowel cancer screening preparation. The standard formulation for bowel preparation is PEG; however, a large dose is required, and it has a distinctive flavour that is considered unpleasant. SP/MC requires a small dose and ensures fluid intake because it is administered in another beverage. Therefore, clinical trials have shown that SP/MC is superior to PEG in terms of acceptability. We aim to compare the novel bowel cleansing method (test group) comprising SP/MC with elobixibat hydrate and the standard bowel cleansing method comprising PEG plus ascorbic acid (standard group) for patients preparing for outpatient colonoscopy. METHODS: This phase III, multicentre, single-blind, noninferiority, randomised, controlled, trial has not yet been completed. Patients aged 40-69 years will be included as participants. Patients with a history of abdominal or pelvic surgery, constipation, inflammatory bowel disease, or severe organ dysfunction will be excluded. The target number of research participants is 540 (standard group, 270 cases; test group, 270 cases). The primary endpoint is the degree of bowel cleansing (Boston Bowel Preparation Scale [BBPS] score ≥ 6). The secondary endpoints are patient acceptability, adverse events, polyp/adenoma detection rate, number of polyps/adenomas detected, degree of bowel cleansing according to the BBPS (BBPS score ≥ 8), degree of bowel cleansing according to the Aronchik scale, and bowel cleansing time. DISCUSSION: This trial aims to develop a "patient-first" colon cleansing regimen without the risk of inadequate bowel preparation by using both elobixibat hydrate and SP/MC. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT; no. s041210067; 9 September 2021; https://jrct.niph.go.jp/ ), protocol version 1.5 (May 1, 2023).

[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.

1-L polyethylene glycol + ascorbic acid versus sodium picosulfate + magnesium citrate bowel preparations for colonoscopy: effectiveness and safety.

BACKGROUND: adequate bowel preparation is crucial for the protective effect of colonoscopy. Commonly used preparation regimens like polyethylene glycol (PEG) or sodium picosulfate with magnesium citrate (SPMC) have shown similar results in clinical trials, but low-volume PEG + ascorbic acid (1-L PEG + ASC) versus SPMC have never been compared in a real-life setting. AIM: to evaluate the effectiveness and safety of 1-L PEG + ASC versus SPMC in a real-life setting for the overall population, for patients aged ≥ 65 years, and males versus females. METHODS: out-patients aged ≥ 18 years who underwent colonoscopy for any indication were randomly assigned to the 1-L PEG + ASC or SPMC group. Using the Boston Bowel Preparation Scale (BBPS), the primary endpoints were the bowel cleansing success of the overall colon and right colon, as well as high-quality (HQ) cleansing. Furthermore, the effectiveness and safety outcomes for age groups and males versus females were compared. RESULTS: 1-L PEG + ASC showed significantly better bowel cleansing success than SPMC. Particularly remarkable is the HQ cleansing reached with 1-L PEG + ASC compared with SPMC (55.5 % versus 25.4 % in the overall colon, and 58.7 % versus 27.2 % in the right colon). 1-L PEG + ASC was equally effective for men and women while SPMC showed significant differences between genders (men had worse bowel cleansing). Age did not affect the cleansing effectiveness. 1-L PEG + ASC versus SPMC showed significant differences in tolerance and safety; women also had significantly worse tolerance than men for both solutions, but these did not affect the quality of bowel cleansing. CONCLUSIONS: in our real-life setting, 1-L PEG + ASC offered better adequate and HQ bowel cleansing than SPMC, achieving excellent cleansing quality, regardless of gender or tolerance.

[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.

[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.