[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.

[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.

[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.

[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.

[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.

[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.

[Neurological manifestations of postcovid syndrome]. / Nevrologicheskie proyavleniya postkovidnogo sindroma.

The problem of postcovid syndrome (PCS) attracts great interest due to the wide prevalence and variety of clinical manifestations. The main neurological manifestations of PCS are considered. The information about the proposed mechanisms of the formation of PCS is given. The possibility of using the drug Mexidol for the treatment of patients with PCS is discussed.

The functional indexes of RBCs and microcirculation in the traumatic brain injury with the action of 2-ethil-6-methil-3-hydroxypiridin succinate.

RESEARCH AIM: To study the RBCs functional and metabolic parameters and the microcirculatory brain structure at traumatic brain injury (TBI) under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate. METHODS: A closed TBI was modeled by the free fall of a load on the parietooccipital regions of head. We made studies of the influence of 2-ethil-6-methil-3-hydroxipiridin succinate on aggregation and electrophoretic mobility of RBCs, catalase activity, malonic dialdehyde concentration, adenosine triphosphate and 2.3-biphosphoglycerate (2.3 - BPG) concentrations in RBCs. The state of parenchyma and microcirculatory brain mainstream in post-traumatic period of TBI have been studied on micro-preparations. RESULTS: The use of 2-ethyl-6-methyl-3-hydroxypyridine succinate under conditions of head injury leads to a decrease in MDA concentration and in aggregation of RBCs, to an increase in the 2.3-BPG concentration and RBC electrophoretic mobility compared to the control (group value). The most pronounced changes under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate were observed 3-7 days after the TBI. Significant indicators of the restoration of the microvasculature and brain tissue provoked by the use of 2-ethyl-6-methyl-3-hydroxypyridine succinate of were evident from the 7th day unlike the control group, where the restoration of structural morphological parameters was observed only on the 12th day of the post-traumatic period. Fast recovery of blood flow under the action of 2-ethyl-6-methyl-3-hydroxypyridine succinate ensured effective restoration of neurons and glia in comparison with the control group. CONCLUSIONS: Early and long-term cytoprotective correction intensifies the oxygen transport function of the blood, prevents and / or reduces disorders of microvessels, neurons and glia in the post-traumatic period, thereby provides correction of hypoxic state and drives to the restoration of brain tissues homeostasis.

[Possibilities of improving the effectiveness of therapy in patients with chronic cerebral ischemia against the background of COVID-19]. / Vozmozhnosti povysheniya effektivnosti terapii patsientov s khronicheskoi ishemiei golovnogo mozga na fone COVID-19.

OBJECTIVE: To study the possibility of improving the efficacy of treatment with mexidol in COVID-19 patients with chronic cerebral ischemia (CCI). MATERIAL AND METHODS: Three hundred and four patients with CCI and COVID-19 were observed, group 1 (n=152) consisted of patients receiving basic therapy and mexidol, group 2 (n=152) received only basic therapy. Mexidol was administered intravenously for 14 days, 500 mg (10 ml) per 400 ml of saline solution, then Mexidol FORTE 250 was administered in a dose of 250 mg 3 times a day for 2 months. The state of cognitive functions (MoCA scale), sleep (Spiegel questionnaire), asthenia (MFI-20 scale), and quality of life (SIP questionnaire) were evaluated. Examinations were performed before treatment, 30 and 75 days after start of treatment. RESULTS: In group 1, there was a more complete and earlier recovery of the state of cognitive functions (an increase in indicators on the MoCA scale, p<0.01), a regression of asthenia (p<0.05), and normalization of sleep (p<0.01). By the end of the study, there were significantly more patients in group 1 with complete or significant recovery of all quality of life indicators. CONCLUSION: Long-term sequential therapy with mexidol provides a more complete recovery of impaired functions in patients with CCI and COVID-19.

Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC).

Persistent androgen receptor (AR) activation drives therapeutic resistance to second-generation AR pathway inhibitors and contributes to the progression of advanced prostate cancer. One resistance mechanism is point mutations in the ligand binding domain of AR that can transform antagonists into agonists. The AR F877L mutation, identified in patients treated with enzalutamide or apalutamide, confers resistance to both enzalutamide and apalutamide. Compound 4 (JNJ-pan-AR) was identified as a pan-AR antagonist with potent activity against wild-type and clinically relevant AR mutations including F877L. Metabolite identification studies revealed a latent bioactivation pathway associated with 4. Subsequent lead optimization of 4 led to amelioration of this pathway and nomination of 5 (JNJ-63576253) as a clinical stage, next-generation AR antagonist for the treatment of castration-resistant prostate cancer (CRPC).

[Efficacy and safety of mexidol across age groups in the acute and early recovery stages of hemispheric ischemic stroke (results of additional sub-analysis of a randomized double blind multicenter placebo-controlled study, in parallel groups trial EPICA)]. / Effektivnost' i bezopasnost' Meksidola u patsientov raznykh vozrastnykh grupp v ostrom i rannem vosstanovitel'nom periodakh polusharnogo ishemicheskogo insul'ta (rezul'taty subanaliza randomizirovannogo dvoinogo slepogo mul'titsentrovogo platsebo-kontroliruemogo v parallel'nykh gruppakh issledovaniya EPIKA).

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) across age groups according to the World Health Organization classification. MATERIAL AND METHODS: The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60-65 years, 76-90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. RESULTS: The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0.001). The decrease in mean mRS score (Visit 1-5) was more prominent in patients aged 60-65 years (p=0.025), including patients with diabetes mellitus (DM). Patients aged 76-90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0.049 and p=0.02) and an increase in patients without problems with everyday activities (p=0.007 and p=0.02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0.023) and quality of life (p=0.045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. CONCLUSION: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM.

[The efficacy and safety of Mexidol Forte 250 as part of long-term sequential therapy in patients with carotid stroke]. / Éffektivnost' i bezopasnost' preparata Meksidol Forte 250 v ramkakh dlitel'noi posledovatel'noi terapii u bol'nykh s ishemicheskim insul'tom v karotidnoi sisteme.

AIM: To evaluate an effect of long-term sequential therapy with mexidol and mexidol forte on the functional outcome of patients with carotid ischemic stroke. MATERIAL AND METHODS: The study included 50 patients with newly developed carotid stroke, hospitalized in the stroke unit on the first day from the onset of the disease. Patients of the main group (n=25) received mexidol in a dose of 500 mg intravenously once a day for 14 days, then mexidol forte 250 in tabs 250 mg 3 times a day for 60 days. Patients of the comparison group (n=25) received standard basic therapy. The significance of intergroup differences was assessed using the Mann-Whitney test, Fisher's exact test, and relative risk (OR) calculation. Differences were considered significant at a level of p<0,05. RESULTS: After 14 days of therapy, both groups of patients showed a positive trend compared to baseline. At the same time, patients of the mexidol group had a higher MoCA score (U=173,5, p=0,006), a lower score when performing tasks on dynamic praxis (U=214,0, p=0,028) and optical spatial disturbances (U=170,5, p=0,003), better memorization strength (181,5, p = 0,006) and better performance on abstraction MOCA subtest (U=200,5, p=0,014). By the 74th day, the absence of moderate cognitive impairment (MoCA> 26 points) was diagnosed in 17 patients (68%) of the main group and 14 patients (56%) of the comparison group. No significant differences were found. Moreover, patients of the main group had a significantly lower NIHSS score (U=124,0, p<0,001) and a lower degree of disability: a total mRS score 0-2 was achieved in 19 (76%) patients of the main group and only in 12 (48%) patients of the comparison group (OR=3,34, F=0,07, p<0,05). Also, patients receiving long-term sequential therapy with mexidol and mexidol forte 250 had milder spatial disorders than patients of the comparison group. CONCLUSION: Consecutive treatment with mexidol and mexidol forte 250 in the acute and early recovery periods of ischemic stroke positively affects the regression of local neurological symptoms, increases the likelihood of achieving independence in everyday life by 3,34 times, and reduces the severity of optical-spatial, neurodynamic and memory impairments.

[Results of the sequential use of Mexidol and Mexidol Forte 250 in patients with chronic cerebral ischemia]. / Rezul'taty posledovatel'nogo primeneniia preparatov Meksidol i Meksidol Forte 250 u bol'nykh s khronicheskoi ishemiei golovnogo mozga.

AIM: To study the efficacy and safety of mexidol's intravenous injections (500 mg once a day) for 14 days, followed by oral administration of mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days, in treatment of chronic cerebral ischemia (CCI) in patients with hypertension and atherosclerosis of the brachiocephalic arteries. MATERIAL AND METHODS: The observation program included 60 patients with an established diagnosis of CCI confirmed by neuroimaging methods. Patients of the main group (n=26) received mexidol along with basic therapy, patients of the comparison group (n=26) received only basic therapy. RESULTS AND CONCLUSION: The results of the experience show the high efficacy and safety of sequential therapy (parenteral therapy followed by tablets of mexidol FORTE 250). The treatment improves emotional and cognitive status, decreases static-motor disorders and severity of subjective neurological symptoms. High adherence of patients to the therapy is shown.

[Efficacy and safety of the drug mexidol FORTE 250 as part of sequential therapy in patients with chronic ischemia of the brain]. / Éffektivnost' i bezopasnost' preparata Meksidol FORTE 250 v ramkakh posledovatel'noi terapii u patsientov s khronicheskoi ishemiei mozga.

AIM: To study the efficacy and safety of mexidol dripped intravenously (500 mg once a day) in the form of infusions for 14 days, followed by oral administration of mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days, in treatment of chronic brain ischemia in patients with hypertension and atherosclerosis. MATERIAL AND METHODS: The open observation program included 60 patients with an established diagnosis of chronic brain ischemia confirmed by neuroimaging methods. RESULTS AND CONCLUSION: The results of the study show the high efficacy and safety of sequential therapy (injections followed by tablets of mexidol FORTE 250). The treatment improves emotional and cognitive status, decreases motor disorders and severity of subjective manifestations. High adherence of patients to the therapy is shown.

[Evaluation of blood rheology by patients with acute ischemic stroke with Mexidol administration]. / Otsenka reologicheskikh pokazatelei krovi u patsientov s ostrym ishemicheskim insul'tom pri primenenii preparata meksidol.

To study rheological properties of blood in patients with acute ischemic stroke treated with mexidol. MATERIAL AND METHODS: Sixty patients with acute stroke, including 32 patients who received mexidol (500 mg/IV/20 days) and 28 people who received magnesium sulfate (2000 mg/IV/20 days) were examined. The control group included 20 people without a cardiovascular pathology. Blood rheology (viscosity of whole blood, plasma viscosity, hematocrit, aggregation and deformability of erythrocytes, fibrinogen level) was evaluated in patients three times: for the first 12 hours, 3-5 days and 18-20 days after hospitalization. RESULTS: Hyperviscosity syndrome was observed in all patients with stroke. A significant decrease in blood viscosity was found in patients treated with mexidol: in the 3-5th day at low shear rates and in the 18-20th day at 3-100 s-1 shear rates. Significant differences in hematocrit (p=0.026) and fibrinogen levels (p=0.017) in patients treated with different drugs were found in the 18-20th day of the disease. Higher erythrocyte deformability index was recorded in patients treated with mexidol in the 3-5th day at shear rates of 90 and 890 s-1, in the 18-20th day at shear rates of 90-360 s-1. CONCLUSION: The study confirms the impact of mexidol on the fluidity of blood during the acute cerebral ischemia and shows its efficacy in reducing blood viscosity, decreasing the level of hematocrit and fibrinogen, increasing the deformability of erythrocytes.

Linker Optimization and Therapeutic Evaluation of Phosphatidylserine-Targeting Zinc Dipicolylamine-based Drug Conjugates.

We report that compound 13, a novel phosphatidylserine-targeting zinc(II) dipicolylamine drug conjugate, readily triggers a positive feedback therapeutic loop through the in situ generation of phosphatidylserine in the tumor microenvironment. Linker modifications, pharmacokinetics profiling, in vivo antitumor studies, and micro-Western array of treated-tumor tissues were employed to show that this class of conjugates induced regeneration of apoptotic signals, which facilitated subsequent recruitment of the circulating conjugates through the zinc(II) dipicolylamine-phosphatidylserine association and resulted in compounding antitumor efficacy. Compared to the marketed compound 17, compound 13 not only induced regressions in colorectal and pancreatic tumor models, it also exhibited at least 5-fold enhancement in antitumor efficacy with only 40% of the drug employed during treatment, culminating in a >12.5-fold increase in therapeutic potential. Our study discloses a chemically distinct apoptosis-targeting theranostic, with built-in complementary functional moieties between the targeting module and the drug mechanism to expand the arsenal of antitumor therapy.

[Combined administration of mexidol with known medicines]. / Kombinirovannoe primenenie meksidola s izvestnymi lekarstvennymi sredstvami.

This review summarizes the available data on the combined administration of mexidol with medicines of different pharmacotherapeutic groups. Mexidol has a multifaceted mechanism of action and exhibits a wide range of pharmacological effects. It enhances therapeutic effects of a variety of drugs in research and clinical settings, boosts the effectiveness of therapy prescribed in accordance with the applicable federal standards and contributes to reducing the severity of complications. Effectiveness data and pathogenetic considerations underpinning combination therapy with mexidol and other drugs suggest that this is a viable approach for treating cerebrovascular and cardiovascular diseases, diseases of the nervous system, open-angle glaucoma and alcohol intoxication as well as a number of other diseases.

A randomized clinical prospective trial comparing split-dose picosulfate/ magnesium citrate and polyethylene glycol for colonoscopy preparation.

BACKGROUND: Colonoscopy remains the gold standard for the investigation of abnormalities within the colon. However, its success is highly dependent on the quality of bowel preparation. The objective of this study was to compare the bowel preparation efficacy of picosulfate/magnesium citrate (PMC) vs polyethylene glycol (PEG) in a one-day vs two-day split dose regimen. METHODS: A prospective, randomized, controlled trial was conducted at the Forzani & MacPhail Colon Cancer Screening Centre in Calgary, Canada. 171 colonoscopy outpatients were randomized to split-dose PMC or PEG lavage as well as into one-day split or two-day split regimens in blocks of eight. Bowel preparation quality was recorded in a blinded manner by the endoscopist using the Ottawa Bowel Preparation Scale (OBPS) prior to washing or suctioning. The scale results were analyzed using a two-factor analysis of variance. RESULTS: 141 patients received complete colonoscopies (PMC-71; PEG-70). PEG was found to be superior to PMC (mean OBPS: 4.14 ± 2.64 vs 5.11 ± 3.44, p = 0.019), when adjusted for administration regimen, leading to significantly more adequate bowel preparations (79.7% vs 59.7%, p = 0.007). A two-day split dose was superior to a one-day split dose regimen (mean OBPS: 3.68± 2.82 vs 5.69 ± 3.06, p<0.001). Two-day split dosing also resulted in a better right colon cleanliness score (right bowel OBPS 1.27±0.11 vs 2.10±0.12 for one-day split, P<0.001). CONCLUSIONS: Optimal bowel preparation was achieved with the use of PEG lavage when administered in a two-day split dose regimen. This trial is registered with ClinicalTrials.gov under identifier NCT01415687.