Liposomal form of dexamethasone in the correction of experimental acute lung injury

Objective. To investigate the possibility of pharmacological correction of acute lung injury of aspiration genesis with a liposomal form of dexamethasone in experiment. Materials and methods. For the experiment, simple liposomes were prepared from phosphatidylcholine and cholesterol with an average size of 320±50 nm and a dexamethasone concentration of 2.98±0.02 mg/ml. The study used outbred white rats, divided into four groups of 16 animals. 1st group Control (without experimental therapy), 2nd group - Experiment 1, where a solution of dexamethasone was injected intravenously at a dose of 6 mg/kg, 3rd group - Experiment 2, where an intravenous combination of dexamethasone solution (6 mg/kg) and hypertonic (7.5%) NaCl solution was administered once, and group 4 - Experiment 3, where liposomes with dexamethasone (6 mg/kg) were injected intravenously once in hypertensive (7.5%) NaCl solution. The main functional parameters of the animals (heart rate, blood pressure, saturation of hemoglobin with oxygen, partial pressure of blood oxygen and respiration rate) were subject to analysis. Functional parameters were analyzed before modeling acute lung injury and after 5 min, 1, 4, 24 hours, and 6 days. At the end of the experiment (day 6) the degree of pulmonary edema and histological signs of acute lung injury were assessed. Morphology was assessed quantitatively in each group. Results. The study found that liposomal dexamethasone in hypertonic NaCl solution, when administered intravenously, was more effective than aqueous dexamethasone solution in correcting functional impairment in acute lung injury. The combination of hypertonic sodium chloride solution with dexamethasone more markedly increases blood pressure and reduces the degree of pulmonary oedema. In acidine pepsin aspiration, liposomal dexamethasone in hypertonic NaCl solution most effectively increased animal survival. Conclusion. Compared with dexamethasone in hypertonic NaCl solution, liposomal dexamethasone is more effective in increasing animal survival and protecting lung tissue from aspiration damage by acidine pepsin.

The role of compliance in the treatment of chronic heart failure and the ways to improve it

Despite the development and implementation of clinical guidelines, emergence of modern effective drugs for the treatment of chronic heart failure (CHF), this pathology is characterized by stable progression, directly worsening the quality of life and decreasing the life expectancy. With that, treatment efficacy directly depends on high treatment compliance in patients with CHF both at the treatment start and upon its subsequent correction. One should also not underestimate the value of patient readiness to modify their lifestyle. Besides, the complete physician compliance with clinical guidelines also plays a significant role. The absence of correspondence between principles defined in the guidelines and really administered drugs excludes the possibility of achieving control over CHF symptoms and positive impact on the prognosis. This review is aimed at evaluating treatment compliance among both patients with CHF and their physicians with a focus on Russian studies and good clinical practice (GCP) compared to studies of foreign authors. Unfortunately, the problem of compliance in CHF in the Russian Federation has not been sufficiently analyzed in large-scale studies up to the present time: CHF patient registries mainly allow to detect clinical and epidemiological disease features, while almost not covering compliance issues. It should also be noted that the problem of compliance in both physicians and patients is undoubtedly up-to-date, as it often defines further prognosis in patients with CHF, which explains the scientific practical value of large trials with subsequent thorough analysis and searches regarding increasing its efficiency.

Estimation of the level of endothelial factor of vascular growth and monocytic chemoattractant in children cerebral palsy

Objective. The aim of this article is to assess the role of vascular endothelial growth factor and monocytic chemoattractant in the development of cerebral palsy in children. Materials and methods. Examination of 77 children with different clinical forms of infantile cerebral palsy in the age group from 1 to 16 years was carried out. The content of monocyte chemoattractant (MCP) and vascular growth factor (VEGF) was determined in different forms of cerebral palsy. The obtained data were processed statistically. Results. The analysis of the obtained data revealed a significant increase in the indicators of monocytic chemoattractant and vascular growth factor in children with infantile cerebral palsy compared with healthy children. There were no significant differences between the indicators of MCP and VEGF in children with cerebral palsy and comorbid pathology and children with cerebral palsy without concomitant pathology. Conclusion. The authors of the presented analysis conclude that the determination of monocytic chemoattractant and vascular growth factor has a high diagnostic value for identifying a predisposition to the development of cerebral palsy. Timely detection of an increase in the level of these factors provides a broader prospective for early diagnosis of the disease and for the early implementation of rehabilitation measures accordingly.

The role of neurotrophic proteins as prognostic markers of neurological, functional and cognitive impairments in the acute period of cerebral infarction in patients with sleep apnea

The objective: to evaluate the diagnostic efficacy of neurotrophic proteins BDNF, NGF, NT3 as prognostic markers of neurological, functional and cognitive impairments in the acute period of cerebral infarction in patients with and without sleep apnea. Materials and methods. 52 patients were examined in the first 72 hours from the onset of cerebral infarction (CI). The survey included an assessment on the NIHSS, mRs and MOSA scales (in the first 72 hours and after a month); study of the concentration of proteins BDNF, NGF, NT3 in plasma by enzyme immunoassay and respiratory polygraphy. The patients were divided into the main group (32 patients with sleep apnea (SA)) and the comparison group (20 patients without SA). The control group consisted of 32 patients without CI and SA. Results. In patients of main group at the end of the acute period of CI threshold concentrations of BDNF ≤1605.2 pg/ml (AUC - 80%), NGF ≤697.37 pg/ml (AUC - 78%) and NT3 ≤400.7 pg/ml (AUC - 70%) were established as effective prognostic markers of an unfavorable functional outcome (MRs≥3); BDNF ≤1994.8 pg/ml (AUC - 75%) - of severe neurological deficit (NIHSS> 4); BDNF ≤1724.7 pg/ml (AUC - 76%) and NGF ≤858.55 pg/ml (AUC - 73%) - of the presence of cognitive impairments (MOCA <26). In patients of the comparison group the threshold concentration of BDNF protein ≤1189.6 pg/ml was established as an effective prognostic marker of unfavorable functional outcome (AUC - 85%) and severe neurological deficit (AUC - 80%). Conclusion. Neurotrophic proteins have good indicators of diagnostic accuracy as prognostic markers of neurological, functional, and cognitive impairments at the end of the acute period of CI in patients with and without SA.

Role of transforming growth factor beta in tumor process

The study and application of representatives of the transforming growth factor-beta (TGF-β) family in practical medicine remains an urgent task at the present time. A more detailed study of the properties and activity of proteins related to TGF-β opens up new possibilities in the treatment and diagnosis of diseases associated with skeletal muscles, female reproductive system, oncology and the cardiovascular system, as well as in the development of drugs based on them. This work examines the role of TGF-β in tumor development and the potential of this protein as a therapeutic target, as well as the signaling pathway, various marker proteins, and various types of receptors involved in this process. During tumor development, TGF-β uses two pathways: the classic SMAD-dependent pathway and the non-SMAD-dependent pathway. In the early stages of tumorigenesis, TGF-β acts as a tumor suppressor, causing a cytostatic effect and apoptosis in normal and pre-malignant cells. However, after tumor development, TGF-β functions as a tumor promoter, triggering the transition of the epithelium to the mesenchyme, which leads to increased invasiveness and the development of metastases. The role of TGF-β in oncogenesis in various organ systems has been studied, including in breast, colon, stomach, hepatocellular carcinoma, thyroid cancer, etc. Specifically, TGF-β1 causes a wide range of different physiological reactions, regulates development, differentiation, carcinogenesis and tumor progression of epithelial cells, has multiple effects on the entire process of hematopoiesis. Directions for the creation of drugs for the treatment of tumors targeting TGF-β are presented.

Predicting the shape of the obturator foramen in the surgical treatment of stress urinary incontinence in women

The aim of the study was to study the possibility of predicting the shape of the obturator foramen depending on the shape of the pelvic bone cavity in the aspect of the surgical treatment of stress urinary incontinence in adult women. Materials and methods. 61 preparations of the female bone pelvis were studied. A pelviometric form was developed, according to which the linear and angular parameters of the pelvis and obturator foramen, indices of the pelvic cavity and obturator foramen were evaluated. A discriminant analysis was applied to classify the shapes of the obturator foramen. Results. Based on the calculated pelvic cavity indices, the shape of the pelvic cavity was determined: narrowing to the bottom, cylindrical and widening to the bottom. Using discriminant analysis, a model was developed to predict the shape of the obturator foramen, depending on the shape of the pelvis. Two main forms of the obturator foramen are distinguished: triangular and elliptical. It was found that the triangular form of the obturator foramen is most characteristic of the cylindrical form of the pelvic cavity and to a lesser extent of the downwardly tapering form. The ellipsoidal shape of the obturator foramen predominated in the downwardly expanding pelvic cavity. It is also shown that a narrow under-pelvic angle is characteristic of the downward pelvic cavity and a wide under-pelvic angle is characteristic of the downward dilating pelvis. Conclusion. The presented index of the lateral deviation of the ischial tubercles makes it possible to determine the shape of the pelvic cavity: narrowing to the bottom, cylindrical and dilating to the bottom. The method of discriminant analysis provides a high degree of certainty in predicting the shape of the obturator foramen, depending on the shape of the pelvic cavity.

Change in the value of the QT interval at various stages of the perioperative period in patients with coronary ischemic heart disease under general anesthesia

Objective. To evaluate the status of QT interval derivatives in patients with chronic IHD during different perioperative periods of planned open cholecystectomy under general anaesthesia and to determine the possibility of using meldonium for prevention of QT interval dysfunction. Materials and methods. Patients with the diagnosis of cholelithiasis with verified forms of chronic CHD (angina I and II AC) were divided into 2 groups: Group 1 was the control group with conventional perioperative therapy, and Group 2 was the main group with additional meldonium. The dynamics of the corrected QT interval (QTc) and the variance of the QT interval (DQT) were assessed. Analysis was performed by means of daily Holter ECG monitoring, in which 6 time periods were singled out: 1 - the day before the operation (18 hours); 2 - hours before the operation; 3 - induction into anesthesia; 4 - maintenance of anesthesia; 5 - withdrawal from anesthesia; 6 - the day 2 after the operation (18 hours). Results. The increase in QTc and DQT values during induction, maintenance and withdrawal from anesthesia was detected only in the control group. The inclusion of meldonium in perioperative therapy in patients with CHD was accompanied by the absence of QTc interval prolongation and an increase in DQT values in the periods of induction, exit and maintenance of anaesthesia. Conclusion. The perioperative period was accompanied by a prolongation of the QTc interval and an increase in DQT values in the group receiving conventional therapy. The inclusion of meldonium was accompanied by no increase in QTc and DQT during most follow-up periods.

Effect of glyprolines on serum caspase levels under “social” stress

Objective. To investigate the effect of glyprolines on the levels of initiating and effector caspases in the serum of white rats under "social" stress. Materials and methods. The study was conducted on 90 white male rats of 6 months of age. All manipulations with animals were carried out in accordance with international and domestic requirements for working with laboratory animals. When modeling "social" stress, groups of animals with aggressive and submissive behavior were formed. Laboratory animals, taking into account the types of behavior, were divided into groups (n=10): a group of intact males (control); a group of animals exposed to" social " stress for 20 days (stress); groups of individuals who received intraperitoneal Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), Pro-Gly-Pro, Pro-Gly-Pro-Leu at doses of 100 mcg/kg / day from the 1st day of stress exposure within a 20- day course. The effect of neuropeptides on the activity of apoptosis processes was evaluated by determining the level of initiating and effector caspases (caspase-8 and caspase-3) (ELISA Kit for Caspase-8 and ELISA Kit for Caspase-3; USA) in the blood serum of white rats by enzyme immunoassay. Results. According to the results of the study, it was found that under conditions of "social" stress, an increase in apoptotic processes was observed, accompanied by an increase in the level of caspase-3 and caspase-8 in the blood serum of white rats. The introduction of the studied compounds against the background of stress contributed to a decrease in the level of the studied indicators, which is most likely due to the presence of antiapoptotic action in glyprolins due to inhibition of the caspase-dependent cascade of apoptosis reactions, as a result of which the destruction of cellular structures occurs by hydrolysis of nuclear lamina, cleavage of adhesive proteins, destruction of the cytoskeleton. Conclusion. Thus, the conducted study established the presence of Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selank), Pro-Gly-Pro and Pro-Gly-Pro-Leu under conditions of stress-induced antiapoptotic activity due to inhibition of the caspase-dependent cascade of apoptosis reactions.

Senna leaves: component composition, pharmacological properties, standardization

Objective: generalization and analysis of scientific data on the component composition, pharmacological properties and standardization of senna leaves. Materials and methods. The article provides an overview of scientific publications in the journals of the search platforms Scopus and PubMed, as well as the databases of the Russian Science Citation Index. The analysis of the range of herbal medicinal products was carried out according to the data of the State Registers of Medicines of the Republic of Belarus, the Russian Federation and the Republic of Kazakhstan using content analysis, comparison and generalization of data. Results. In addition to the laxative effect, determined by the presence of anthracene derivatives in senna leaves, the complex of their biologically active substances has antimicrobial, hypoglycemic, antioxidant, antifungal and antitumor effects. Also, the chemical composition of the plant is represented by fatty acids, triglycerides, flavonoids, macro- and microelements. The analysis of medicinal herbal preparations based on senna leaves registered in the Russian Federation, the Republic of Belarus and the Republic of Kazakhstan has been carried out. The differences in the methods of their standardization, given in the normative documentation on quality, have been revealed. The scientific experience of using the method of high performance liquid chromatography for the determination of anthracene derivatives in senna leaves is generalized. Conclusion. The complex of biologically active substances of senna leaves exhibits various pharmacological effects, which, possibly, will expand the range of combined preparations based on them. The use of a modern and selective method of high-performance liquid chromatography in the analysis of senna leaves is a very promising direction in the field of standardization of this type of medicinal plant material.

Pharmacological correction of antioxidant protection system in the brain with Vincamine within the model of multiple sclerosis

Objective. In the course of the research, the effect of vincamine (nootropic drug) on neurological status, as well as the activity of antioxidant enzymes and the level of their coding genes’ expression in the somatosensory cortex of rats within the model of experimental allergic encephalomyelitis (EAE) were being studied. Relevance: the topicality of studying the mechanisms of multiple sclerosis in the early stages of its development is dictated by the need to search for markers of the disease and its therapy before the onset of its clinical manifestation. Materials and methods. The animals’ neurological status was studied using muscular strength, balance, tenacity and traction tests. Rates of survival and the rats’ body weight were also being evaluated. The study of activity antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPO), and glutathione reductase (GR), as well as the expression of SOD1, GPX4, GPX6, and GSR genes was conducted on the 14th and 30th day of immunization. Results. The percentage of vincamine-injected animals’ survival was 100% versus 87% among rats that were not injected with the nootropic drug during immunization (р<0,05) . Besides, after the injection of vincamine, a less significant decrease in body weight (р<0,01) and a less pronounced neurological deficit (р<0,05) in comparison with immunized non-injected animals were reported. The vincamine injection contributed to an increase in all studied antioxidant enzymes’ activity and the level of their genes’ expression in the somatosensory cortex. Conclusion. Against the background of vincamine injection, a minimization of neurological deficit is being observed, probably due to a decrease in oxidative stress in the rat brain during the clinical stage of experimental allergic encephalomyellitis.