The effect of nanodispersions with lipoic acid and its esters on the activity of lactate dehydrogenase in neutrophils and platelets has been studied. It has been shown that nanoparticles with lipoic acid and its esters decrease the activity of lactate dehydrogenase in neutrophils and platelets 1.5–2 times, which indicates that nanodispersions containing lipoic acid and its conjugates decrease the concentration of reactive oxygen species in activated neutrophils and platelets 2–3 times. Studies on the inhibition of free radical processes in neutrophils and platelets showed that the nanoforms with lipoic acid and its esters possess an antioxidant activity.

Nanoemulsions (NEs) with lipoic acid (LA) with a particle size from 50 to 350 nm were obtained, characterized by 85±10% efficiency of inclusion (EF) of LA into nanoparticles (NPs), its slow release from nanoforms, and also having high stability during long-term storage at room temperature. Nanoemulsions containing LA have been shown to suppress platelet aggregation (Pt) caused by arachidonic acid (AA).

Synthesis of new derivatives of α-lipoic acid (α-LA) with glutathione was carried out to increase their therapeutic effect, protect against biodegradation and prolonged release of α-LA and glutathione from the obtained compounds these substances.

Various nanodispersions (liposomes and nanoemulsions) with lipoic acid (LA) with size of particles 50-250 nm were obtained and characterized by 80±10% encapsulation efficiency (EI) of LA into NPs, its slow release from nanoconstructions, and possessing stability during long-term storage at room temperature. It was revealed that liposomes and LA NPs inhibit platelet aggregation caused by arachidonic acid, and the mechanism of antiplatelet action was proposed.

OBJECTIVE Evaluation of the effect of local therapy with Kapsikam on the dynamics of clinical symptoms and indices of the disability scale, as well as on reducing the doses of systemic non-steroidal anti-inflammatory drugs (NSAIDs) used in patients with acute back pain (LOCUS study). MATERIALS AND METHODS An observational study included 120 patients with nonspecific pain in the lower back and a verified diagnosis of Lumbodynia M54.5; «Lumbodynia with sciatica» M54.4, of which 78 received in addition to the basic treatment with systemic NSAIDs topical drug Kapsikam and 42 - only basic treatment. Results and conclusion. The addition of Kapsikam ointment to systemic NSAIDs accelerated the onset of the analgesic effect, which made it possible to discontinue NSAIDs in 50% of patients after 5 days of use. Local therapy was accompanied by easily tolerated adverse events that did not affect the use of the drug. 97.4% of patients used the study drug as prescribed until the end of the study.

We describe the dynamics of lipoic acid (LA) alone, incorporated in liposomes and as a part of nanoemulsions. Mass spectrometry shows that LA in water forms aggregates of two or three molecules in the form of a negatively charged ion and a neutral molecule. Phosphatidylcholine (PC)-based nanoforms of LA as liposomes and nanoemulsions with a particle size equal to 145 nm are characterized by a high degree of incorporation of LA into the nanoparticles and long-term stability during storage at room temperature. Dynamic light scattering (DLS) gives the polydispersity index of the nanoforms (> 0.3), characterizing the homogeneity of the obtained nanodispersions. We found that such emulsions can significantly (5 ×) increase the concentration of LA in the aqueous phase (5–7 mg/mL) when compared with an aqueous solution of LA (1 mg/mL) and by 40% when compared with PC liposomes (4 mg/mL). Moreover, the inclusion of LA in liposomes and nanoemulsions from PC did not change the neutral ζ-potential characteristic of PC nanoforms. CryoTEM established that the structural organization of the liposomes practically did not differ from nanoemulsions and both nanoforms contained both multilayer and single-layer vesicles. When studying the release kinetics of LA from phosphatidylcholine nanoforms, we found that at 22 h, 45–55% of LA was released from nanoparticles, but that at the initial stage of the process LA was slowly released from the nanoemulsions and rapidly from the liposomes. Conductance measurements indicate that LA delivered in all the three forms increase membrane permeability, though this result is most marked with the LA in PC liposomes.

Objectives. To study oxidative stress in young patients with focal symptomatic and cryptogenic epilepsy and after first onset of epileptic seizures. Materials and methods. A total of 90 patients aged 19–44 years took part in the study and were divided into three groups of 30 patients after single epileptic seizures, with clinical remission for one year or more, and treatment-resistant epileptic seizures. The study also included presumptively healthy people (20 subjects) who made up the control group. Study indicators were prooxidant stress in terms of TBA-active products and antioxidant defense in terms of total plasma superoxide-scavenging activity, catalase activity, total plasma antioxidant activity, and reduced plasma thiols (SH groups). Results. No significant differences were found in the plasma TBA-active products concentration between epilepsy patients and the control group. The other study parameters (concentration of reduced SH groups, total plasma superoxide-scavenging activity, catalase activity) and total plasma antioxidant activity showed significant differences from controls. Significant between-group differences were found for a number of indicators. Conclusions. Changes in free-radical processes compared with normal were seen after first seizures and persisted in refractory epilepsy and in clinical remission. Given that measures of the activity of the antioxidant defense system showed significant differences between different groups of epilepsy patients, it can be suggested that different components of oxidative stress are activated after first epileptic seizures and in different courses of epilepsy.

Подобраны условия для получения фосфатидилхолиновых липосом, содержащих одновременно липоевую кислоту и карнозин. Полученные липосомы представляют собой сферические частицы размером 180-250 нм, характеризующиеся эффективностью включения липоевой кислоты, равной 50-70%, и карнозина - 17-33%. На модели окисления фосфатидилхолина пероксидом водорода показано антиоксидантное действие карнозина, липоевой кислоты или липоевой кислоты с карнозином совместно, заключающееся в торможении процесса липидной пероксидации, которое проявляется в уменьшение образования продуктов перекисного окисления липидов, реагирующих с тиобарбитуровой кислотой. Установлено, что липоевая кислота (5 мМ) и карнозин (0.1-10 мМ) в липосомах проявляют антиоксидантное действие. При этом было показано, что содержание соответствующих продуктов липидной пероксидации в липосомах с антиоксидантами (липоевая кислота + карнозин) было в 15 раз меньше, чем в контрольных липосомах (без антиоксидантов). Оценено влияние полученных липосомальных препаратов на агрегацию тромбоцитов, индуцированную арахидоновой кислотой. Обнаружено, что липосомальный препарат, содержащий липоевую кислоту (1.5 мМ) и карнозин (2.1 мМ), подавляет агрегацию тромбоцитов на 50-55% относительно контроля (тромбоциты и арахидоновая кислота), в то время как липосомы без антиоксидантов и водорастворимые формы препаратов карнозина и липоевой кислоты практически не влияют на агрегацию тромбоцитов, обусловленную арахидоновой кислотой.

We present the results of experimental studies on the aggregation of blood cells in platelet-rich plasma in the presence of an aggregation inducer rhystomicin under the effects of low-intensity radiation of extremely-high frequency. Primary alcohols were used as stimulators for partial degradation of protein-lipid bilayer in the cell membrane. The results showed that exposure to radiation of extremely-high frequency reduces the extent of rhystomicin-induced platelet aggregation and changes the angle of inclination of the aggregatogram. This study revealed a two-phase nature of the effects of alcohols on platelet aggregation - the first phase is characterized by a decrease in aggregation and in the angle of inclination of the aggregatogram, the second phase includes an increase in platelet aggregation and in the angle of inclination simultaneously with an increase in the concentration of alcohols in the sample. A possible mechanism underlyinhg the observed effects is under debate.

Objectives. To assess changes in the phospholipid composition of blood plasma in patients with chronic cerebrovascular disease using the neuroprotectors 2-ethyl-6-methyl-3-hydroxypyridine succinate (Neurox) and citocoline (Neipilept), which are natural metabolites and participants in metabolic processes in the body, alone and in combination. Materials and methods. A total of 40 patients (18 men, 22 women) aged 54–72 years took part in the study; patients had chronic cerebrovascular disease in exacerbation on the background of hypertensive crisis and/or impairments to cardiac rhythm. Results. Extraction of lipids from patients’ blood cells revealed significant reductions in the quantities of all (total) lipids after completion of treatment in patients receiving Neurox, Neipilept, and complex treatment using both agents. Studies of the quantitative composition of blood cell phospholipids showed that there were no significant changes in patients taking Neurox, while citicoline, alone and in combination with 2-ethyl-6-methyl-3-hydroxypyridine succinate, led to increases in total quantities. Assessment of the qualitative composition of classes of phospholipids in plasma showed no significant changes in patients taking Neurox, while those receiving Neipilept alone and with 2-ethyl-6-methyl-3-hydroxypyridine succinate showed significant increases in plasma phosphatidylcholine. There were no significant changes in phosphatidylinositol, phosphatidylserine, or sphingomyelin contents.

A fluorescent nanosensor based on colloidal quantum dots CdSe/ZnS modified with mercaptoacetic acid to determine reduced glutathione, a non-protein compound that plays an important role in protection against oxidative stress, is developed. Sample preparation protocols that allow determination of reduced glutathione in a wide range of concentrations are presented. Dependence of the fluorescence intensity of the system on the incubation time for a number of concentrations of reduced glutathione was measured. The possibility of using the proposed nanosensor for reliable and sensitive determination of reduced glutathione in the concentration range from 10 to 1000 μM is confirmed. The results can be used for quantitative determination of reduced glutathione in physiological media, which is of considerable interest for medical diagnostics.

AIMTo assess the changes in the composition of plasma phospholipids in patients with chronic cerebrovascular disease treated with neuroprotectors 2-ethyl-6-methyl-3-hydroxypyridine succinate (neurox) and citicoline (neipilept), the natural metabolites involved in biochemical processes in the body, and their composition.MATERIAL AND METHODSThe study included 40 patients, 18 men and 22 women, aged from 54 to 72 years, with chronic cerebrovascular disease at the decompensation stage complicated with the hypertensive crisis and/or arrhythmia.RESULTS AND CONCLUSIONDuring extraction of phospholipids from blood cells, a significant decrease in the amount of total lipids was found to the end of treatment of patients who received neurox or neipilept or their combination. The study of quantitative composition of phospholipids showed no significant changes in patients treated with neurox, while the use of citicoline or combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate resulted in the increase of their total mass. There were no significant changes in the qualitative composition of phospholipid classes in blood plasma in patients treated with neurox. In patients treated with neipilept or with the combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate, plasma phosphatidylcholine was significantly increased. No significant changes in the content of phosphatidylinositol, phosphatidylserine and sphingomyelin were observed.

AIM:To study an effect of cortexin on neurological symptoms and oxidative stress as part of the ischemic cascade in chronic cerebral ischemia (CCI), I-II stages.MATERIAL AND METHODS:The multicenter randomized controlled study included 189 patients with CCI, 42 (22.2%) men and 147 (77.8%) women, mean age 64.3±0.5 years. Patients were randomized into three groups. Group 1 received intramuscular injection of 20 mg of cortexin, group 2 received 10 mg of cortexin; group 3 received basic treatment only. The duration of treatment was 10 days, the treatment course was repeated after 6 months. The patients were examined at baseline and during treatment (in total 5 times). Along with clinical and neurological examinations, some scales and tests ('Fedin Outpatient scale of chronic brain ischemia', MFI-20, Spiegel sleep scale, the Zung self-rating depression scale, Spielberger's inventory, the clock-drawing test, the 5-word test) were used. The severity of oxidation stress was assessed by the content of reduced SH-groups and total superoxide dismutase activity.RESULTS AND CONCLUSION:A dose-dependent effect of cortexin on the severity of neurological disorders, asthenia, sleep disturbance was shown. Antidepressant and anxiolytic effects were insignificant and were determined after repeated courses of the drug. The laboratory data confirmed the antioxidant effect regardless of the dose of cortexin. The safety and good tolerability of the drug were shown.

The objective was to study the state of vascular walls in young patients at various stages and various courses of epilepsy.Materialsand methods. We examined 62 patients of young age with focal symptomatic and cryptogenic epilepsy for hanges in their blood vessels. Photoplethysmography combined with a non-invasive diagnostic system (“Angioscan Electronics”, Russia) were used. The patients were divided into 3 groups: 1) patients after a single (first) epileptic seizure; 2) patients with remission; 3) patients with treatment-resistant seizures.Results. We found no structural changes in their blood vessels. However, the occlusion test showed changes in the functional state of large muscle arteries in all groups of epileptic patients. In addition, changes in microcirculatory beds were detected in patients after a single seizure and in those resistant to treatment. Patients after single epileptic seizures showed the largest changes in small resistance arteries and arterioles.Conclusion. The results suggest that functional characteristics of vascular endothelium change in young patients suffering from epilepsy.

Показано, что «пустые» фосфатидилхолиновые липосомы и в значительной степени липосомы содержащие α-липоевую кислоту, препятствуют повышению гранулярности тромбоцитов, вызванной арахидоновой кислотой. Используя метод проточной цитофлюометрии обнаружено, что ФХ-липосомы и липосомальная форма α-липоевой кислоты, подавляют флуоресценцию активированных арахидоновой кислотой тромбоцитов, обусловленную окисленными флавопротеинами. Методом флуоресцентной микроскопии установлено, что флуоресцентно-меченные липосомы контактируют с тромбоцитами.

Developing brain ischemia due to cerebral vascularization leads to disruption of brain metabolism. Chronic cerebral hypoperfusion leads to irreversible brain damage and plays an important role in the development of some types of dementia. Early use of antioxidants such as ethyl ether apovincamine acid (vinpocetine) and 2-ethyl-6-methyl-3-hydroxypyridine-succinate in the treatment of this pathology is seen as a real pathogenetically based method of correction of cerebral metabolism with cerebral vascular disorders, demonstrating the increase in cerebral blood flow and also neuroprotective effects. Clinical studies and studies on biological models show that the main mechanisms of action of vinpocetine and 2-ethyl-6-methyl-3-hydroxypyridine-succinate, although have a similar focus, but implementing neuroprotective and nootropic effects via various links in the pathogenesis of ischemic brain damage.

Оценена динамика изменения «пустых» фосфатидилхолиновых (ФХ) липосом и липосом с α-липоевой кислотой при длительном хранении (в течение 18 месяцев) при Т = +4 0С. Изучено взаимодействие липосомальных нанокнструкций с компонентами плазмы здоровых доноров и пациентов, перенёсших острый ишемический инсульт. Методом динамического светорассеяния (ДРС) показано, что инкубирование в течение 4 часов липосомальной формы ЛК в плазме крови здоровых доноров не приводит к изменению размеров диаметров липосом.