Vol 161, No 2 (2016)
- Year: 2016
- Articles: 29
- URL: https://journals.rcsi.science/0007-4888/issue/view/14724
Physiology
Differences in Monoamine Oxidase Activity in the Brain of Wistar and August Rats with High and Low Locomotor Activity: A Cytochemical Study
Abstract
Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity. Comparison of August rats with low locomotor activity and Wistar rats with high motor activity (i.e. animals demonstrating maximum differences in motor function) revealed significantly higher activity of the enzyme (substrates tryptamine and serotonin) in the hippocampus of Wistar rats. The study demonstrates clear-cut morphochemical specificity of monoaminergic metabolism based on the differences in the cytochemical parameter “monoamine oxidase activity”, in the studied brain structures, responsible for the formation and realization of goal-directed behavior in Wistar and August rats.
Article
Effect of NO Synthase Blockade on Myocardial Contractility of Hypokinetic Rats during Stimulation of β-Adrenoreceptors
Abstract
Stimulation of β-adrenoreceptors with low (10–8 and 10–7 M) or high (10–6 M) doses of isoproterenol in hypokinetic rats treated with L-NAME (a non-selective blocker of NO synthases) decreased or increased myocardial contractility, respectively. In control rats, all examined doses of isoproterenol used under blockade of NO synthases inhibited myocardial contractility.
Changes in Behavior and Blood Corticosterone Level in Male and Female Rats after Single Administration of Obestatin Fragment 1-4
Abstract
Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats.
Atrial Natriuretic Peptide Inhibits Spontaneous Contractile Activity of Lymph Nodes
Abstract
Atrial natriuretic peptide dose-dependently inhibited spontaneous phase and tonic activity of smooth muscle strips from the capsule of isolated bovine mesenteric lymph nodes. Pretreatment with L-NAME, diclofenac, and methylene blue had practically no effect on the peptide-induced relaxation responses. In contrast, glibenclamide significantly reduced the inhibitory effect of atrial natriuretic peptide. We suppose that the NO-dependent and cyclooxygenase signaling pathways are not involved in implementation of the inhibitory effects of atrial natriuretic peptide. ATP-sensitive K+-channels of the smooth muscle cell membrane are the last component in the signaling pathway leading to relaxation of smooth muscles of the lymph node capsule caused by atrial natriuretic peptide; activation of these channels leads to membrane hyperpolarization and smooth muscle relaxation.
Dominant and Non-Dominant Frequency Structure of Evoked Ventricular Fibrillation in Dogs with Myocardial Ischemia
Abstract
The first 10 min of electrically provoked ventricular fibrillation in dogs with ischemic heart disease were characterized by organized myocardial activity evidenced by the dominant ECG frequency structure. During the first 2 min of ventricular fibrillation, low-frequency oscillations (4-7 Hz) dominated, while on min 3 to 10 after the onset of fibrillation, the dominant frequencies were low and medium (4-12 Hz). After 10-min fibrillation, the oscillations became non-dominant. Thus, ischemic myocardium maintains the organized structure of ventricular fibrillation for the first 10 min, which is important for the development of automatic diagnostics of abnormal cardiac activity in humans.
Repolarization of Heart Ventricles in Dogs during Recovery after Antiorthostatic Hypokinesia
Abstract
Repolarization properties of ventricular myocardium were studied in anesthetized adult dogs of both sexes subjected to antiorthostatic hypokinesia (head-down tilt at 45° and 60° to the horizontal) and during recovery period (horizontal position for 15 min). The time of repolarization of ventricular myocardium during recovery surpassed the initial value, which represents an adaptive response of the heart to antiorthostasis.
Age-Dependent Changes in Na+,K+-ATPase Activity and Lipid Peroxidation in Membranes of Erythrocytes during Cardiosclerosis Development in Rats
Abstract
Activity of Na+,K+-ATPase was measured in erythrocyte ghosts of 4- and 12-month-old rats, intact and with postinfarction cardiosclerosis. Enhanced accumulation of secondary LPO products and reduced activity of Na+,K+-ATPase were observed in erythrocyte ghosts of 12-month-old rats. The development of postinfarction cardiosclerosis in 4-month-old rats was accompanied by enhanced accumulation of LPO products and decreased activity of Na+,K+-ATPase. In comparison with young rats with postinfarction cardiosclerosis, 12-month-old rats with this pathology were characterized by less pronounced decrease in Na+,K+-ATPase activity and increase in accumulation of LPO products in comparison with intact control.
Cardiac Autonomic Drive during Arterial Hypertension and Metabolic Disturbances
Abstract
ANS support of the cardiac work was assessed with analysis of heart rate variability in representative samples of patients with arterial hypertension and metabolic disturbances manifested by overweight, classes I-II obesity, compromised glucose tolerance, and type II diabetes. Initially enhanced sympathetic effects on the heart rate demonstrated no further increase during the orthostatic test in contrast to suprasegmentary influences enhanced by this test. The pronouncedness of revealed peculiarities in ANS drive to the heart correlated with metabolic disturbances, and these peculiarities attained maximum in patients with type II diabetes.
Radioprotective and Apoptotic Properties of a Combination of α-Tocopherol Acetate and Ascorbic Acid
Abstract
We studied radioprotective and apoptotic properties of a combination of α-tocopherol acetate and ascorbic acid. α-Tocopherol acetate (10 mg/kg body weight) or ascorbic acid (20 mg/kg) or combination of these agents in the same doses was orally administered to male rats at various terms before and after single whole-body exposure to γ-irradiation in the doses of 2 and 8 Gy. Irradiation increased the frequency of chromosome aberrations in bone marrow cells and plasma level of low-molecular-weight DNA. Vitamin combination administered before or after irradiation significantly reduced the frequency of chromosome aberrations by 2-2.5 times. Administration of this combination 10 min before irradiation 1.5-fold increased the content of low-molecular-weight DNA in blood plasma in comparison with the control animals exposed to radiation. The combination of α-tocopherol acetate and ascorbic acid produced radioprotective effects and enhanced apoptosis in irradiated cells.
Preclinical Toxicological Study of Release-Active Preparations for Prediction of Their Pharmacological Activity and Side Effects
Abstract
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.
Effects of Intraperitoneal Administration of Mifepristone on Glucocorticoid Status of Experimental Animals
Abstract
We studied the content of corticosterone and its precursors in the adrenal glands, corticosterone in blood serum and daily urine of rats, and activity of first and second isoforms of 11β-hydroxysteroid dehydrogenase in the liver and kidneys of rats after 15 daily intraperitoneal injections of 0.9% NaCl or glucocorticoid receptor blocker mifepristone in 0.9% NaCl. Daily injections of NaCl reduced the levels of pregnenolone, progesterone, and corticosterone in the adrenal glands, increased corticosterone excretion with urine, enhanced activity of the first isoform of 11β-hydroxysteroid dehydrogenase in the liver and reduction in activity of the second isoform of this enzyme in the kidneys. These changes are typical manifestations of chronic stress. Mifepristone restored pregnenolone content in the adrenal glands and increase in corticosterone concentration in the blood. Under these conditions, activity of the first isoform of 11β-hydroxysteroid dehydrogenase in the liver did not change, and a decrease in activity of the second isoform of the enzyme in the kidneys was less pronounced. The results suggest that mifepristone abolished the stress-mediated increase in activity of the first isoform of 11β-hydroxysteroid dehydrogenase in the liver and reduced local production of glucocorticoid hormones and their metabolic effects in hepatocytes.
Effects of N-[Imino(1-Piperidinyl)Methyl] Guanidine on the Intensity of Free Radical Processes, Aconitase Activity, and Citrate Level in the Tissues of Rats with Experimental Type 2 Diabetes Mellitus
Abstract
Effects of a synthetic biguanide derivative N-[imino(1-piperidinyl)methyl] guanidine (NIPMG) on free radical homeostasis, aconitase activity, and citrate concentration were studied in the liver and blood serum of rats with type 2 diabetes mellitus. Analysis of biochemiluminescence parameters showed that administration of this agent (10 mg/kg body weight) to animals with diabetes reduced the intensity of free radical processes in study tissues relative to the increased values in untreated diabetic animals. Under these conditions, aconitase activity, a principal target of ROS effects, and citrate level in the liver and blood serum of rats approached the control levels. The results show that NIPMG can positively regulate free radical homeostasis and reduce the intensity of oxidative stress in type 2 diabetes mellitus, which was accompanied by normalization of the studied parameters.
IFN-α, IFN-β, and IFN-γ Have Different Effect on the Production of Proinflammatory Factors Deposited in Weibel-Palade Bodies of Endothelial Cells Infected with Herpes Simplex Virus Type 1
Abstract
We demonstrated similarities and differences in the effects of IFN-α and IFN-β compared to IFN-γ on the production of factors deposited in the Weibel-Palade bodies in cultures of endothelial cells (intact and infected with herpes simplex virus 1). IFN-α and IFN-β reduced the content of von Willebrand factor, endothelin-1, and soluble P-selectin and increased IL-8 concentration in the culture medium of human umbilical vein endothelial cells. IFN-γ reduced the content of all studied factors in the endothelial cell culture medium. Possible mechanisms of these effects are discussed.
Evaluation of Oxidative Metabolism in Leukocytes during Phagocytosis of Escherichia coli Carrying Genetic Constructs soxS::lux or katG::lux
Abstract
We studied ROS generation by human peripheral blood monocytes and granulocytes during phagocytosis of Escherichia coli soxS::lux or katG::lux responding by luminescence (bioluminescence) to the development of oxidative stress. Initially high sensitivity of the bioluminescent reaction of E. coli katG::lux strain to the effects of model ROS (KO2 and H2O2) and pronounced induction of luminescence upon contact with granulocytes, whereas E. coli soxS::lux demonstrated less pronounced reaction to chemical oxidants and bioluminescence was observed primarily upon contact with monocytes. A correlation was found between quantitative characteristics of E. coli katG::lux bioluminescence and luminol-dependent chemiluminescence of leukocytes in some patients, but no dependence of this kind was noted for E. coli soxS::lux. The results can provide experimental substantiation of a new approach for evaluation of ROS production by leukocytes during phagocytosis and choosing the optimal object for these studies.
New Carbocyclic Amino Acid Derivatives Inhibit Infection Caused by Highly Pathogenic Influenza A Virus Strain (H5N1)
Abstract
New amino acid derivatives with carbocycles of adamantine and quinaldic acid were synthesized and their in vitro antiviral activity against influenza A/H5N1 virus was evaluated. Experiments on cultured embryonic porcine kidney epithelial cells showed that amino acid derivatives suppressed viral replication. Tret-butyloxycarbonyl-DL-methionylsulfonyl-1-adamantayl ethylamine and benzyloxycarbonyl-L-trypthophanyl-1-adamantayl ethylamine compounds demonstrated high activity in all in vitro experiments. Moreover, some compounds showed virucidal activity against influenza A/H5N1 virus.
Silicon Nanoparticles as Amplifiers of the Ultrasonic Effect in Sonodynamic Therapy
Abstract
The possibility of using mesoporous silicon nanoparticles as amplifiers (sensitizers) of therapeutic ultrasonic exposure were studied experimentally in vitro and in vivo. The combination of nanoparticles and ultrasound led to a significant inhibition of Hep-2 cancer cell proliferation and Lewis lung carcinoma growth in mice. These results indicated good prospects of using silicon nanoparticles as sensitizers for sonodynamic therapy of tumors.
Effects of Vascular Peptide Bioregulator on the Density of Microvascular Network in the Brain Cortex of Aged Rats
Abstract
Using a TV unit for microcirculation studies, we studied the density of the entire microvascular network and its arterial compartment in the pia mater of the sensorimotor cortex in intact young and aged rats (2-3 and 22-24 months) and aged rats after a course of vascular peptide bioregulator Slavinorm. The experiments showed that the density of microvascular network in intact animals decreased by 1.6 times with aging. Treatment with the peptide bioregulator 2.5-fold increased the density of the microvascular network in aged rats in comparison with intact animals of the same age, the density of the arterial compartment of the microvascular network in the pia mater increased by 2.8 times.
Plant Polysaccharides Attenuate Fluorouracil Toxicity for the Small Intestinal Epithelium
Abstract
Polysaccharides from Tussilago farfara L., Acorus calamus L., and Echinacea purpurea (L.) Moench attenuated the toxic effect of fl uorouracil on the small intestinal epithelium of mice with Lewis lung carcinoma. Addition of polysaccharides to chemotherapy protocols stimulated reparative regeneration processes in the small intestine damaged by the cytostatic treatment. No stimulating effects of the polysaccharides on tumor growth and metastasizing were revealed.
Expression of Bax Protein and Morphological Changes in the Myocardium in Experimental Acute Pressure Overload of the Left Ventricle
Abstract
The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochondrial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.
Lentiviral Transduction of Neurons in Adult Brain: Evaluation of Inflammatory Response and Cognitive Effects in Mice
Abstract
We evaluated the effect of hippocampal injection of lentiviral particles p156-CMV-EGFP on behavior, learning, and microglial Iba1+ cells activation in mice. Testing in the open field and elevated plus-maze revealed higher anxiety levels in lentiviral-injected mice in comparison with animals injected with vehicle. At the same time, lentivirus injection did not change learning and memory of mice in the hippocampal-dependent fear conditioning task. Microglia density in lentivirus-injected mice was significantly higher than in vehicle-injected mice. Thus, hippocampal injection of lentiviral particles with minimum content of transgenes produced evident inflammation process, changed anxiety level of experimental animals, but had no effect on hippocampal-dependent learning and memory.
A New Chemiluminescent Method for Evaluation of the Functional Activity of Neutrophils in Patients with Type 2 Diabetes Mellitus
Abstract
Functional activity of neutrophils was evaluated by the chemiluminescent method with successive double stimulation by soluble stimuli with different mechanisms of action: phorbol-12-myristate-13-acetate (PMA) and phormyl-methionyl-leucyl-phenilalanine (fMLP). The study was carried out in 26 patients receiving oral sugar-reducing therapy. In addition to the functional activity of neutrophils, the levels of TBA reactive products, inflammation markers, blood clotting values, and biochemical parameters were measured. The results showed mainly reduction of the granulocytic component of the immune system in the patients.
General Pathology and Pathophysiology
Implication of JAK1, JAK2, and JAK3 in the Realization of Proliferation and Differentiation Potential of Mesenchymal Progenitor Cells In Vitro
Abstract
Involvement of individual JAK kinases in the realization of growth potential of mesenchymal progenitor cells was examined in vitro. Important role of JAK2 and JAK3 in determining the initial level of mitotic activity of progenitor cells was established. The yield of fibroblast CFUF was suppressed under the effect of specific inhibitors of JAK kinases. Blockade of JAK3 increased the rate of progenitor element differentiation. JAK1 had no effect on proliferation and differentiation status of progenitor cells.
Biophysics and Biochemistry
Effect of Audiogenic Seizures on the Dynamics of Fatty Acid Composition of Hippocampal Dental Gyrus in Krushinsky-Molodkina Rats
Abstract
Changes in the fatty acid composition of the hippocampal dentate gyrus in Krushinsky–Molodkina rats with hereditary predisposition to audiogenic seizures were studied in 1, 3, and 14 days after 1 or 5 seizures. Seizure activity changed the content of saturated and monounsaturated as well as polyunsaturated fatty acids at different terms after seizures. After seizures, the content of individual fatty acids changed in different directions. Similar shifts after 1 and 5 seizures were observed only for eicosapentaenoic acid at all observation terms. More pronounced changes in fatty acid composition were observed after 5 seizures. These results can be useful for the development of new approaches to correction of seizure activity.
Pharmacology and Toxicology
Neuroprotective Effectiveness of Intravenous Ubiquinone in Rat Model of Irreversible Cerebral Ischemia
Abstract
The neuroprotective effect of ubiquinone (coenzyme Q10)was demonstrated on the rats model of ischemic stroke provoked by persistent 24-h occlusion of the middle cerebral artery. Coenzyme Q10 (30 mg/kg) was injected intravenously in 60 min after artery occlusion. Ubiquinone crossed the blood-brain barrier, accumulated in the brain, and produced a neuroprotective effect: it alleviated ischemia-induced neurological deficit and reduced the size of necrotic zone by 49% in comparison with rats receiving physiological saline.
Microbiology and Immunology
Effect of Antidepressants on Immunological Reactivity in ASC Mice with Genetically Determined Depression-Like State
Abstract
The effect of chronic treatment with antidepressant drugs fluoxetine (20 mg/kg) and imipramine (25 mg/kg) on the number of antibody-producing cells and the main T cell subpopulations in ASC mice characterized by genetic predisposition to depression-like states was studied at the peak of the SE-induced immune response (5×108). Fluoxetine produced an immunostimulatory effect manifested in an increase in the relative and absolute number of IgM antibody-producing cells in the spleen and index of immunoreactivity (CD4/CD8). Administration of fl uoxetine to parental mouse strains without depression (CBA and AKR) had no effect (CBA) or reduced the immune response. The CD4/CD8 ratio did not increase under these conditions. Imipramine was ineffective in the correction of immune reactions in a depression-like state.
Virology
Effect of Hepatitis C Virus Coinfection on the Content of CD4+ and CD8+ T Cell Subpopulations in HIV-Infected Patients Receiving Antiretroviral Therapy
Abstract
We studied the effect of hepatitis C virus coinfection on T cell subpopulations in HIV-infected patients receiving antiretroviral therapy. Coinfection with hepatitis C virus was followed by a decrease in the number of naive CD4+ T cells and an increase in the count of central CD8+ memory T cells in these patients. Hepatitis C virus had no effect on the number of CD4+ memory T cells (main target for HIV). This can explain the absence of strong negative effect of hepatitis C virus on the course of HIV infection.
Oncology
Comparative Evaluation of β-Catenin and E-Cadherin Expression in Liquid Aspiration Biopsy Specimens of Thyroid Nodules
Abstract
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.
Biotechnologies
Relationship between the Size of Magnetic Nanoparticles and Efficiency of MRT Imaging of Cerebral Glioma in Rats
Abstract
BSA-coated Fe3O4 nanoparticles with different hydrodynamic diameters (36±4 and 85±10 nm) were synthesized, zeta potential and T2 relaxivity were determined, and their morphology was studied by transmission electron microscopy. Studies on rats with experimental glioma C6 showed that smaller nanoparticles more effectively accumulated in the tumor and circulated longer in brain vessels. Optimization of the hydrodynamic diameter improves the efficiency of MRT contrast agent.
Morphology and Patholorphology
Morphofunctional Changes in the Tibial and Peroneal Nerves in Shin Lengthening Using High Speed Daily Distraction Technique
Abstract
A sustained decrease in the M-response amplitudes of m. gastrocnemius and m. tibialis anterior was revealed during experimental orthopedic shin lengthening in dogs using Ilizarov external fixator with an automated drive (distraction 3 mm/day in 120 steps). Transverse contraction of intrafascicular content (by 13.2%), endoneural hypervascularization (by 28-95%), axonal degeneration and myelin decompactization, and destructive changes of no more than 5% fibers were detected in the tibial nerve. In the peroneal nerve, the contraction reached 17.3%. Endoneurium hypovascularization (by 12%), axonal degeneration and demyelinization, and destructive changes of more than 20% fibers were detected in 6 of 9 experiments.