Synthesis, structure, and biological activity of 4-hetaryl-2-pyrrolidones containing a pyrazole ring.

Unlabelled: Single diastereomers of 4-hetaryl-2-pyrrolidone-3(5)-carbo- and 2-[4-hetaryl-2-pyrrolidon-1-yl]acetohydrazides were used in reactions with 2,4-pentanedione, providing (3,4)-3-, (4,5)-5-(3,5-dimethyl-1-pyrazole-1-carbonyl)- and 1-[2-(3,5-dimethyl-1-pyrazol-1-yl)-2-oxoethyl]-4-hetaryl-2-pyrrolidones. The structures of the synthesized compounds were confirmed by spectral methods and X-ray structural analysis. Some of the obtained compounds were shown to possess nootropic and anxiolytic activity.

Effects of Gaba Derivatives on Anxious and Compulsive Behavior in Offspring of Rats with Experimental Preeclampsia.

We studied the effects of GABA derivatives on anxious and compulsive behavior of progeny of rats with experimental preeclampsia provoked by replacement of drinking water for 1.8% NaCl solution from the first day of pregnancy to delivery. In comparison with progeny of health rats, the offspring of dams with complicated pregnancy demonstrated high level of anxiety and the development of obsessive-compulsive disorder both at the early (40 and 70 days) and late (6 and 12 months) stages of ontogeny.

Effects of Levofloxacin on Blood Lymphocyte Apoptosis in Patients with Pulmonary Tuberculosis: an In Vitro Study.

The effects of a fluroquinolone levofloxacin on apoptosis of peripheral blood lymphocytes from patients with infiltrative pulmonary tuberculosis were studied in vitro. It was found that levofloxacin stimulated apoptotic cell death in tuberculosis. Addition of levofloxacin to cell suspension from patients with drug-susceptible form of tuberculosis led to an increase in the number of CD95+ and AnnV+ lymphocytes.

Expression of Galectins-1 and Galectin-3 in Stomach and Colorectal Cancer with Tissue Eosinophilia.

We analyzed the expression of galectin-1 and galectin-3 in tumor tissue in stomach and colorectal cancer with and without tissue eosinophilia. Low expression of galectin-3 was detected in all patients with malignant gastrointestinal tumors irrespective of the presence of eosinophilia. Low expression of galectin-1 was detected only in patients with gastrointestinal cancer associated with eosinophilia.

Survival of Mesenchymal Stem Cells in Different Methods of Nebulization.

We compared survival of bone marrow mesenchymal stem cells after compressor, ultrasound, and mesh nebulization of the cell suspension over 10 min. Viability of stromal cells was best preserved after compressor nebulization (72%). Cell survival after ultrasonic nebulization was significantly lower (20%).

Comparative Evaluation of β-Catenin and E-Cadherin Expression in Liquid Aspiration Biopsy Specimens of Thyroid Nodules.

We compared the results of gene molecular and immunocytochemical studies of β-catenin and E-cadherin in different variants of nodular thyroid disease (nodular colloid goiter, follicular thyroid adenocarcinoma, papillary thyroid cancer) and revealed changes of the function of the E-cadherin/β-catenin complex leading to switching from adhesion function of β-catenin in nodular colloid goiter to predominantly transcriptional activity in papillary carcinoma. The results confirm the important role of disturbances in E-cadherin-β-catenin interactions in the mechanisms of malignant transformation of follicular epithelium.

Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.

[β-Catenin: Structure, Function and Role in Malignant Transformation of Epithelial Cells].

The article presents the data on the structure and mechanisms of β-catenin functioning. The basic aspects of the role of β-catenin in malignant transformation have been studied at various tumors. Primary structure of β-catenin allows it to interact with many factors and ligands, including transcription factors, α-catenin, cadherin, Axin, Rho family GTPases, Bcl9 et al.

[Clinical and immunological comparisons of therapeutic regimens for corneal infiltrates secondary to adenoviral keratoconjunctivitis].

Unlabelled: The problem with post-adenoviral corneal infiltrates is that they cause a significant and persistent decrease in visual function, while corticosteroids in monotherapy bring only temporary improvement.

Aim: to perform a comparative evaluation of topical corticosteroids and 0.05% cyclosporine A efficacy in the treatment of post-adenoviral corneal infiltrates on the basis of clinical presentation and local cytokine status.

[Comparative Analysis of DNA Sequences of Regions of X-Chromosome Attachment to the Nuclear Envelope of Nurse Cells Anopheles messeae Fall].

Polytene chromosomes of ovarian nurse cells of Anopheles mosquitoes form strong contacts with the nuclear envelope. The presence of contacts, their position at nurse cell chromosomes, and their morphological features are species-specific in malaria mosquitoes. It is important to determine the nature of these interspecies differences in the nuclear architecture, both to understand the function of the nucleus and to assess the role of the spatial organization of chromosomes in evolution.

[FREQUENCY-TEMPORAL STRUCTURE OF HUMAN ELECTROENCEPHALOGRAM IN THE CONDITION OF ARTIFICIAL HYPOGRAVITY: DRY IMMERSION MODEL].

Frequency-temporal electroencephalogram (EEG) reactions to hypogravity were studied in 7 male subjects at the age of 20 to 27 years. The experiment was conducted using dry immersion (DI) as the best known method of simulating the space microgravity effects on the Earth. This hypogravity model reproduces hypokinesia, i.

Effects of a New Glutamic Acid Derivative on Myocardial Contractility of Stressed Animals under Conditions of Nitric Oxide Synthesis Blockade.

Glufimet (glutamic acid derivative) in a dose of 28.7 mg/kg limited the reduction of the cardiac functional reserve in animals subjected to 24-h stress under conditions of nonselective NO synthase blockade with L-NAME (10 mg/kg). Adrenoreactivity and increased afterload tests showed that the increment of myocardial contraction/relaxation rates, left-ventricular pressure, and HR were significantly higher in glufimet-treated stressed animals with NO synthesis blockade than in animals which received no glufimet.

[Regulation of the genes expression of CD4+ T-lymphocytes differentiation transcription factors by galectin-3 in vitro].

Now a number of CD4+ T-lymphocytes, known as Th1, Th2, Treg and Th17, is currently identified and well- studied. The methods basing on the targeted regulation of differentiation process of the Th-lymphocytes that carry out the immune response polarization attract an attention of scientists dealing with a correction of immune-mediated. In the present study, endogenous beta-galactoside-binding protein of the lectin family, galectin-3, was investigated as a regulator of T-cell homeostasis.

Effect of GABA derivatives on the rate of thrombus formation, platelet aggregation, and plasma coagulation capacity in rats with experimental gestosis.

Experimental gestosis induced by replacement of drinking water with 1.8% NaCl promoted hypercoagulation, increased the rate and degree of platelet aggregation, and reduced clotting time in pregnant females. GABA derivatives, compounds RGPU-151, RGPU-152, and phenibut normalized parameters of hemostasis and platelet aggregation and the rate of thrombus formation in the animals.

[Cardioprotective properties of new glutamic acid derivative under stress conditions].

The effect of new glutamic acid derivative on the cardiac ino- and chronotropic functions has been studied in experiments on rats exposed to 24-hour immobilization-and-pain stress. It is established that glutamic acid derivative RGPU-238 (glufimet) at a dose of 28.7 mg/kg increases the increment of myocardial contractility and relaxation rates and left ventricular pressure in stress-tested animals by 13 1,1, 72.

The effects of galectin-1 on the gene expression of the transcription factors TBX21, GATA-3, FOXP3 and RORC.

CD4(+) T cells orchestrate the immune response by differentiating into T helper (Th) or regulatory (Treg) cell subsets that secrete distinct sets of cytokines. They also play a critical role in the pathogenesis of autoimmunity, asthma, allergy and, likely, cancer. The mechanisms involved in the regulation of CD4(+) T cell homeostasis by galectin-1 remain poorly characterized.

[Blood vessels in human dermis during aging].

A factor that potentially influences on skin aging is blood supply which determines global conditions for an organ or a tissue functioning, including skin. Scientific data on conditions of blood supply in the skin during aging are insufficient and contradictory. Therefore, this work was aimed to the study of age-related changes in the number of blood vessels in the human dermis.

[Use of cyclosporine 0.05% in various ocular surface disorders].

It is proved that chronic ocular surface inflammatory disease (including allergic blepharitis, recurrent chalyazia, punctuate keratitis, recurrent herpetic corneal erosions, late stages of adenoviral keratoconjunctivitis, etc.) takes part in the development of secondary dry eye syndrome (DES). However, therapies for inflammation-induced impairment of tear production do not provide long-term control of inflammatory process.

Effect of galectin-1 on apoptosis of CD4(+) lymphocytes differentiated in vitro towards regulatory T cells.

We studied the effect of galectin-1 on apoptosis of CD4(+) lymphocytes intact and in vitro differentiated towards regulatory T cells. An increase in the content of apoptotic CD4(+) lymphocytes was observed after exposure of intact cells with 15 ng/ml galectin-1 and after exposure of regulatory T cells with 10 and 15 ng/ml galectin-1. Apoptosis of regulatory T cells induced by galectin-1 was accompanied by an increase in the content of proapoptotic protein Bad.

[Comparative analysis of action of beta-phenyl derivatives of glutamic and gamma-aminobutyric acid on cerebral blood flow and cerebrovascular endothelium after irreversible occlusion of the common carotid artery].

A comparative analysis of the effect of phenyl derivatives of glutamic (RGPU-135) and gamma-aminobutyric acid (Phenibut) on cerebral blood flow, vasodilatory endothelial function and the number of circulating endothelial cells desquamated in animals after irreversible occlusion of the common carotid arteries. It was found that animals treated prophylactically by RGPU-135, after occlusion of the common carotid arteries have higher cerebral blood flow and lower the severity of endothelial dysfunction than in animals treated with Phenibut.

[Age-related changes in mast cells and eosinophils of human dermis].

In this study, quantitative analysis of inflammatory effectors--mast cells and eosinophils--in derma of people of different ages is performed. The study shows that mast cell quantity in derma increases with age. Eosinophils are rarely observed in human dermis.

[Effect of GABA derivative--RSMU-151 on the development of oxidative stress in rats with experimental gestosis].

Experimental gestosis induced in rats by drinking 1.8% sodium chloride solution instead of water during the entire period of pregnancy leads to activation of lipid peroxidation (LPO) process, as manifested by increased concentration of diene conjugates and malonic dialdehyde, decreased concentration of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in homogenates of rat brain, liver, uterus, and placenta. The GABA derivatives--RSMU-151 limits the damaging effect of gestosis, which is manifested by a decrease in the concentration of LPO products and by activation of the antioxidant system enzymes in all organs studied.

[Fenibut and its citrate prevent psychoneurological disorders caused by chronic stress (paradoxical sleep deprivation)].

The antistress protective action of two structural analogs of GABA, fenibut and its salt with citric acid (fenibut citrate, citrocard, RGPU-147), has been studied using a model of chronic stress caused by seven-fold 24-h deprivation of paradoxical sleep phase at an interval of 24 h between the deprivations. It is established that fenibut and fenibut citrate produce a protective action by (i) reducing the intensity of emotional disorders in the open-field test and elevated plus maze test, (ii) decreasing cognitive disorders in the tests for conditioned avoidance response and extrapolatory deliverance; and (iii) limiting stress reaction due to a decrease in the intensity of adrenal hypertrophy, thymus involution, and stomach mucous membrane ulceration. Fenibut citrate surpasses fenibut in the intensity of antistress protective action.

Genetic variation in glutathione S-transferase genes and risk of nonfatal cerebral stroke in patients suffering from essential hypertension.

Oxidative stress resulting from an increased amount of reactive oxygen species and an imbalance between oxidants and antioxidants has been implicated in pathogenesis of cerebral stroke. The purpose of this study was to investigate the relationship between common polymorphisms of glutathione S-transferase M1, T1, and P1 genes and risk of stroke in hypertensive individuals. A total of 667 unrelated Russian individuals with hypertension, including 306 hypertensives who suffered from cerebral stroke and 361 hypertensives who did not have cerebrovascular accidents, were recruited for the study.