[Targeting NMDAR/AMPAR: a promising pharmacotherapeutic approach for depressive disorders]. / Targetirovanie NMDAR/AMPAR ­ perspektivnyi podkhod farmakokorrektsii depressivnykh rasstroistv.

Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

[Fixed ratio combinations GLP-1RA and basal insulin: literature review].

The progressive nature of type 2 diabetes mellitus leads to the need for insulin therapy in a significant proportion of patients. Very often start of insulin therapy in type 2 diabetes mellitus (T2DM) is associated with weight gain and a significant increase of hypoglycemia's risk. However, innovative options, such as fixed ratio combinations of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulin, minimize weight gain and hypoglycemia risks and allow a greater proportion of patients to achieve individual glycemic control goals without compromising safety parameters. This review includes a description of the randomized clinical trials, as well as the results of real clinical practice of the use of two currently existing fixed ration combinations of GLP-1RA and basal insulin - iDegLira and iGlarLixi.

[Antioxidant effect of cortexin, cerebrolysin and actovegin in rats with chronic cerebrovascular insufficiency]. / Antioksidantnoe deistvie Korteksina, Tserebrolizina i Aktovegina u zhivotnykh s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To compare the antioxidant effects of cortexin, cerebrolysin and actovegin in rats with chronic brain ischemia. MATERIAL AND METHODS: Chronic brain ischemia was modeled in male rats by 50% stenosis of the common carotid arteries. Forty days after surgery, the animals received 2 ten-day courses of therapy, separated by a break of 10 days. Placebo, cortexin (0.3, 1 and 3 mg/kg), cerebrolysin (0.8, 2.5 and 7.5 ml/kg) and actovegin (5 ml/kg) were administered to animals as treatment. The concentration of malondialdehyde (MDA) in the homogenates was determined by the reaction with thiobarbituric acid, the concentration of reduced glutathione was determined by the reduction reaction of 5.5-dithiobis- (2-nitrobenzoic acid); determination of catalase activity, as well as the content of lactate and pyruvate, by commercially available reagent kits. The activity of superoxide dismutase (SOD) was determined by the photometric method based on an assessment of the degree of inhibition of the epinephrine oxidation reaction. All reactions were carried out in triplicates. RESULTS: Modeling of chronic brain ischemia led to the statistically significant decrease in the content of lactate and pyruvate (p<0.001, when compared with the control group), which was not accompanied by a significant decrease in their ratio (p>0.05), as well as to the decrease in SOD, catalase activity, restored glutathione and increase in MDA concentrations. Compared with the control group, in the groups that received cortexin at a dose of 3 mg/kg/day, cerebrolysin at a dose of 7.5 ml/kg/day and actovegin at a dose of 5 ml/kg/day, there were an increase in the content of lactate and pyruvate (without a significant change in their ratio), restoration of glutathione levels and the activity of SOD and, to a lesser extent, catalase, combined with a decrease in the concentration of MDA. CONCLUSION: Course administration of cortexin (3 mg/kg), cerebrolysin (7.5 ml/kg) and, to a lesser extent, actovegin (5 ml/kg) has a positive effect on the state of the antioxidant system of the brain in rats with chronic brain ischemia.

Mycobacterium vaccae Lysate Induces Anti-Allergic Immune Response In Vitro.

Mycobacterium vaccae is a soil saprophyte which exerts anti-allergic properties. There are data that mechanism of action of M. vaccae when used in the treatment of human and animal allergic diseases is associated with Th1-phenotype switch. Here we studied the properties of sonicated M. vaccae lysate in co-cultures of dendritic cells and CD4+T cells. M. vaccae lysate stimulated IL-10 synthesis in co-cultures and CD86 expression in dendritic cells, being more potent than heat-killed M. vaccae. The reported clinical data and the mechanism of action of M. vaccae lysate suggest that its use is a feasible option for the primary prevention of allergic diseases, in particular atopic dermatitis.

Effects of a New Benzimidazole Derivative with Actoprotective Properties on Spermatogenic Epithelium of the Testes and Fertility of Male White Rats.

The effects of a new derivative of benzimidazole (K-134) in doses of 5 and 50 mg/kg on the spermatogenesis and fertilizing ability of spermatozoa were studied on male rats. It was found that 2-month course treatment with the studied substance enhances the producing ability of the spermatogenic epithelium and improves fertilizing ability of spermatozoa.

[Behavioral phenotyping in rats during the experimental modeling of chronic cerebral circulation disorder]. / Povedencheskoe fenotipirovanie krys pri éksperimental'nom modelirovanii khronicheskogo narusheniia mozgovogo krovoobrashcheniia.

AIM: To describe motor, adaptive and cognitive disorders in rats with chronic cerebral circulatory deficiency caused by partial stenosis of the common carotid arteries (CCA). MATERIAL AND METHODS: A study was performed on 20 white outbred male rats. This manipulation led to 40-45% and 50-60% reduction of blood flow in CCA and in the brain, respectively. Twenty days after operation, animal's condition was assessed in the following tests: open field test, rotarod performance test, marble burying test and novel object recognition. RESULTS AND CONCLUSION: After 20 days of experimental CCA stenosis, animals demonstrated several signs of neuropsychiatric deficiency including coordination disorders, a decrease in locomotor activity as well as in explorative and protective behavior. The model of CCA partial stenosis could be used during further studies of the pathophysiology and pharmacology of chronic cerebral circulatory deficiency.

Preclinical Toxicological Study of Release-Active Preparations for Prediction of Their Pharmacological Activity and Side Effects.

We studied chronic toxicity of a few release-active preparations: Dietressa (release-active preparation of affinity-purified antibodies to type 1 cannabinoid receptor), Divasa (releaseactive preparation containing a combination of affinity-purified antibodies to brain-specific S-100 protein and endothelial NO-synthase), Cardostin (release-active preparation containing a combination of affinity-purified antibodies to C-terminal fragment of angiotensin II type 1 receptor and endothelial NO-synthase), and Bation (release-active preparation containing a combination of affinity-purified antibodies to IFN-γ and CD4). We evaluated not only side and toxic effects, but also the relationships between these effects and pharmacological activities of the preparations. The data of preclinical toxicological studies of the release-active preparations can be used for prediction of their pharmacological activity.

Development of Clinical Pharmacology in the Russian Federation.

PURPOSE: The article aims to provide the history, organization, and approaches to clinical pharmacology in the Russian Federation. METHODS: This article is based on major international and Russian documents, along with groundbreaking historical facts and scientific articles related to the development of modern clinical pharmacology the Russian Federation. FINDINGS: Improving the quality of drug therapy is the main goal of clinical pharmacology in the Russian Federation. Decisions of the World Health Organization, scientific achievements, and the work of well-known scientists among the world community and in the Russian Federation have strongly influenced the development of clinical pharmacology the Russian Federation. Clinical pharmacology in the Russian Federation addresses a wide range of problems; it actively engages in modern scientific research, education; and clinical practice. Clinical pharmacologists participate in studies of new drugs and often have a specific area of expertise. IMPLICATIONS: The future development of clinical pharmacology in the Russian Federation will be related to improvements in training, refinement of the framework that regulates clinical pharmacologists, and the creation of clinical pharmacology laboratories with modern equipment.

[Changes in the structure of pathogens of calculous pyelonephritis complicated with diabetes mellitus type ii, in the hospital urology of the city of Volgograd].

Among the diseases complicating the course of calculous pyelonephritis, are among the leaders of diabetes mellitus, which is associated with reduced immune response, deterioration of renal hemodynamics, the reduced sensitivity to antibacterial drugs. The purpose of the study is to improve the results of treatment of patients with calculous pyelonephritis and diabetes mellitus type 2. The materials and methods of research. We studied 179 people. This was a retrospective pharmaco-epidemiological analysis of medical records of patients who were treated in 2009 and 2013, in hospital of Volgograd. Women in the study was greater than 99(by 55.4%), males - 80 (44,6%). All patients underwent standard clinical examination, with mandatory bacteriological urine analysis, ultrasound study of kidneys. RESULTS: During the observation period of 2009 and 2013 in patients with calculous pyelonephritis and type 2 diabetes, the major pathogens were representatives of the family Enterobacteriaceae. E.coli strains are constituted - 12 (54,5%), K. pneumoniae - 4 (18.1%) strains. In other etiologically significant microorganisms were Enterococcus spp. - 3 (13.6%) strain, P. aeruginosa - strain 2 (9%). The group of other (4.5%), we have carried pathogens isolated in the singular: Erobacter spp, S. aureus, and Klebsiella oxytoca. In patients with infection of the upper urinary tract and diabetes, there is a pronounced trend to decrease sensitivity to all groups of antibiotics. Sensitivity to unprotected penicillins and fluoroquinolones has decreased almost twice. Resistance to aminoglycosides of patients in this group increased by 23%. In patients with chronic calculous pyelonephritis and diabetes mellitus type 2 is high sensitivity of the main causative agents of infection to cephalosporins of the third and fourth generation (92%), protected beta-lactam penicillins (amoxicillin/clavulanate) - 86,4%, to carbapenemam is 89.4%. CONCLUSIONS: For the empiric treatment of infections of the upper urinary tract in patients with diabetes mellitus, can be recommended drugs: protected beta-lactam penicillins, cephalosporins of the third and fourth generation, carbapenem.

Effects of Impaza on the Generative Function of Female Rats.

The effects of impaza on ovulatory cycles, sexual behavior, and conception processes were studied in female rats. A two-week course of impaza in doses of 3 and 15 ml/kg did not affect alternation of estrous cycle phases, the incidence of estrus reducing. Sexual behavior of these females was characterized by activation of the receptive sexual motivations; conception was characterized by a higher fertility index and a lower fetal mortality.

Effects of a New Benzimidazole Derivative on Generative Function of Female Rats.

The effects of a new thietanylbenzimidazole derivative (K-134) on estrous cycles, conception processes, and sexual behavior of female rats were studied. Two-week oral treatment with K-134 in doses of 5 and 50 mg/kg shortened the estrus phase and prolonged proestrus. Changes in sexual behavior were presented by activation of receptive sexual motivations without affecting proceptive motivations. The pregnancy and fertility indexes in experimental females after mating with intact males increased and pre- and postimplantation embryonic death decreased.

[Influence of magnesium deficiency correction on the effectiveness of bronchial asthma pharmacotherapy in children].

We have performed 24-week open-labeled comparative randomized parallel-group study of the basic therapy efficacy of uncontrolled and partly controlled atopic asthma children with magnesium deficiency. The additional correction of magnesium deficiency increases the efficacy of atopic asthma basic therapy. It leads to more pronounced inhibition of local allergic inflammation in respiratory system, decreases the exacerbation frequency (9.5%, p = 0.02), and increases the number of asymptomatic days and the 12-week constant asthma control frequency (71.4%, p = 0.145) as compared to the group without magnesium deficiency correction.

[The place of novel oral anticoagulants in prevention and treatment of venous thromboembolism]. / Mesto novykh peroral'nykh antikoaguliantov v profilaktike i lechenii venoznykh tromboémbolii

The notion "venous thromboembolism" combines two processes: thrombosis of deep veins and pulmonary artery thromboembolism. The necessity in long-term adequate anticoagulant therapy as the basic treatment of patients with deep vain thrombosis does not give rise to doubts, it should be started prior to instrumental verification of the diagnosis. The past decade was marked by the appearance on the pharmaceutical market of a new oral anticoagulant: selective blocker of the Xa factor of blood coagulation system - rivaroxaban. According to the data of large-scale randomized clinical trials, the efficacy and safety of rivaroxaban are comparable to those of traditional conventional anticoagulant therapy (non-fractionated/low-molecular-weight heparin NFH/LMW + warfarin). Indisputable advantages of new agents are as follows: the lack of the necessity in laboratory monitoring, no interaction with foodstuff, minimal interaction with other drugs, minimal risk for the development of haemorrhage, and simplicity of dosing.

Experimental study of the efficiency of Dietressa preparation on body weight reduction in mice feeding high-fat ration.

We studied the efficiency of Dietressa on body weight reduction in C57Bl/6 male mice feeding standard high-fat ration (24%). After 5-month daily intragastric administration of Dietressa, body weight gain was the lowest in comparison with other groups and did not differ from that in mice receiving the reference substance sibutramine for 5 months. In contrast to sibutramine, Dietressa did not increase motor activity of animals in the open field test and produced no anorectic effect. The mean body weight gain per each 1000 kcal of consumed food in the group of animals receiving Dietressa was lower than in the control group and mice receiving sibutramine.

Antiaggregant activity of a new benzimidazole derivative.

Antiaggregant activity of a new tricyclic benzimidazole derivative, RU-891 compound, was studied on the model of ADP-induced platelet aggregation in vitro and intravascular platelet aggregation in vivo. We evaluated the effect of this substance on blood coagulation potential. Antiaggregant agent acetylsalicylic acid was used as the reference drug. RU-891 produced a dose-dependent antiaggregant effect in vivo and in vitro that exceeded the effect of the reference drug. This compound did not modulate blood coagulation potential.

[Fundamental bases of search of medicines for therapy of a diabetes mellitus type 2].

In the presented review the data on searching for new drugs for diabetes mellitus treantment are analyzed. These drugs are used for metabolic disorder correction leading to hyperglycemia: beta-cells dysfunction, peripheral insulin resistance, increased hepatic glucose output.

[The choice of pharmaceuticals for the treatment of bronchial asthma and chronic obstructive respiratory disease].

This pharmacoepidemiological study at the regional level permitted to reveal the real strategy of medical prescriptions and the choice of medications for the treatment of bronchial asthma and chronic obstructive respiratory disease. Regional variations in the combination of preparations actually used by patients with these diseases are investigated for the first time. The main causes of non-compliance with medical prescriptions are analysed.