![Open Access](https://journals.rcsi.science/lib/pkp/templates/images/icons/text_open.png)
![Restricted Access](https://journals.rcsi.science/lib/pkp/templates/images/icons/text_unlock.png)
![Restricted Access](https://journals.rcsi.science/lib/pkp/templates/images/icons/text_lock.png)
Vol 162, No 1 (2016)
- Year: 2016
- Articles: 40
- URL: https://journals.rcsi.science/0007-4888/issue/view/14754
Physiology
Paradoxical Effect of NMDA Receptor Blockade in Chicks on Learning and Memory in Passive Avoidance Model
Abstract
Activity of NMDA receptors is a prerequisite for numerous but not all forms of neuronal plasticity and learning. The present study examined the role of NMDA receptors in standard, weak, and repeated passive avoidance training in young chicks. Injection of MK-801, an antagonist of NMDA receptor, prior to strong training episode impaired subsequent memory recall. Moreover, repeated training did not restore the lost memory. In the double weak training protocol, the impairing effect of MK-801 was observed only when it was injected prior to the second but not to the first training episode. These results suggest that activation of NMDA receptors is not a necessary stage for memory acquisition in the weak training task. In contrast, the mechanisms of strong training depending on activation of NMDA receptors can be probably involved into the second training episode performed against the background of existing NMDA receptor-independent memory about the first training episode.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Article
Peculiar Aspects in Influence of α1-Adrenoceptor Stimulation on Isolated Rat Heart
Abstract
The study examined the effect of α1-adrenoceptor stimulation with methoxamine on chronotropic function of isolated heart perfused ex vivo according to Langendorff and cardiac chronotropy in vivo. Stimulation of α1-adrenoceptors in isolated heart induced gradually developing bradycardia, which progressed during several minutes. Similar stimulation in vivo produced a short-term bradycardia probably terminated by the compensatory influences in the whole organism. Comparison of the data obtained in both experimental paradigms during α1-adrenoceptor stimulation revealed unidirectional changes in cardiac chronotropy characterized with time-related peculiarities.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Cardiac Body Surface Potentials in Rats with Experimental Pulmonary Hypertension during Ventricular Depolarization
Abstract
The spatial and the amplitude-temporal parameters of cardiac body surface potentials were examined in female Wistar rats with experimental pulmonary hypertension during ventricular depolarization. The cardiac body surface potentials have been led from 64 subcutaneous electrodes evenly distributed across the chest surface prior to and 4 weeks after subcutaneous injection of a single dose of monocrotaline (60 mg/kg). Right ventricular hypertrophy and electrophysiological remodeling of the heart developed in rats with experimental pulmonary hypertension in 4 weeks after monocrotaline injection; these changes led to a significant increase in amplitude and temporal characteristics of the cardioelectric field on the body surface in comparison with the initial state.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Possible Cause of Nonlinear Tension Rise in Activated Muscle Fiber during Stretching
Abstract
Tension in contracting muscle fiber under conditions of ramp stretching rapidly increases, but after reaching a critical stretch Pc sharply decreases. To find out the cause of these changes in muscle fiber tension, we stopped stretching before and after reaching Pc and left the fiber stretched for 50 msec. After rapid tension drop, the transient tension rise not accompanied by fiber stiffness increase was observed only in fibers heated to 25°C and stretched to Pc. Under other experimental conditions, this growth was absent. We suppose that stretch of the fiber to Pc induces transition of stereo-specifically attached myosin heads to pre-power stroke state and when the stretching is stopped, they make their step on actin and generate force. When the tension reaches Pc, all stereospecifically attached myosin heads turn out to be non-stereospecifically, or weakly attached to actin, and are unable to make the force-generating step.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Hypolipidemic Effect of Mannan in Mice with Acute Lipemia Induced by Poloxamer 407
Abstract
We studied biological effects of mannan, a polysaccharide immunomodulator from C. albicans, that interacts with mannose receptor in vivo. It is shown that preliminary administration of mannan (5 times in a dose of 50 mg/kg or 2 times in a dose of 100 mg/kg) to mice with acute lipemia induced by lipase inhibitor poloxamer 407 (300 mg/kg) reduces the serum concentrations of atherogenic LDL, cholesterol, and triglycerides. Administration of mannan to intact mice and animals with acute lipemia reduces triglyceride concentration and causes labilization of lysosomal membranes in the liver. Serum activity of chitotriosidase, a marker of macrophage activation, was elevated in mice with acute lipemia treated with mannan. Thus, mannan from C. albicans is a promising hypolipidemic polysaccharide compound, similar by its activity to β-glycan, a component of LPS.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Endomorphins and β-Endorphin Do Not Affect Heart Tolerance to the Pathogenic Effect of Reperfusion
Abstract
Selective agonists of μ1- and μ2-opioid receptors endomorphin-2 and endomorphin-1 injected intravenously in a dose of 4500 nmol/kg in 5 min before coronary blood flow resumption had no effect on cardiac reperfusion damage. Consequently, μ1- and μ2-opioid receptors are not involved in the regulation of heart tolerance to reperfusion injury. Nonselective opioid receptor agonist β-endorphin (100 nmol/kg) also did not affect heart tolerance to the pathogenic effect of reperfusion.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
CB-Receptor Agonist HU-210 Mimics the Postconditioning Phenomenon of Isolated Heart
Abstract
CB receptor agonist HU-210 exhibits an infarction-limiting effect during in vitro reperfusion of the heart after focal ischemia. This effect is paralleled by a decrease in left-ventricular developed pressure and double product. In addition, HU-210 reduces end-diastolic pressure during the reperfusion period, which indirectly attests to reduced Ca2+ overload of cardiomyocytes.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Features of the Left Ventricular Functional Geometry in Patients with Myocardial Diseases with Varying Degrees of Systolic Dysfunction
Abstract
We revealed some features of the left ventricular functional geometry in patients with myocardial diseases with different degrees of left ventricular systolic dysfunction. A negative correlation was found between the spatio-temporal heterogeneity of the kinetics of the left ventricular wall during systole and ejection fraction in normal heart and in systolic dysfunction. The differences in the quantitative characteristics of the functional geometry between patients and normal subjects and between different groups of patients depended on the severityof left-ventricular systolic dysfunction. In particular, spatial heterogeneity index that characterizes heterogeneity of systolic movement of the wall segments and end-systolic Fourier shape-power index characterizing complexity of the left ventricle shape during systole differed significantly in the examined groups of patients and have the greatest diagnostic power.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
2-Morpholino-5-Phenyl-6H-1,3,4-Thiadiazine Corrects Metabolic Disorders during the Development of Alloxan Diabetes Mellitus in Rats
Abstract
Metabolic disorders were evaluated in rats with alloxan diabetes mellitus after administration of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine (compound L-17). Administration of L-17 reduced the severity of metabolic disorders associated with diabetes mellitus. At the end of the experiment, the concentration of glucose, glycated hemoglobin, malonic dialdehyde, and catalase activity were significantly higher and peroxidase activity was significantly lower in the group of animals receiving L-17. The decrease of glycemia, glucose concentration, and glycated hemoglobin content was reached by the 3rd-4th week of the experiment. These data suggest that correction of biochemical parameters in rats with alloxan diabetes was reached after administration of L-17 for at least 3 weeks.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Effectiveness of Lifestyle Modification in Corrections of States Associated with Metabolic Syndrome
Abstract
In a 3-month study, 30 obese patients were assigned to lifestyle modification therapy, which is the major component of all modern strategies correcting the metabolic syndrome. The 3-month course of non-pharmacological therapy significantly diminished the major index evaluating the state of these patients, i.e., the risk of cardiovascular disasters. This therapy positively affected all the states associated with metabolic syndrome: arterial BP attained the targets in 53% patients together with normalization of their nocturnal arterial BP dipping status; the lipid panel and carbohydrate metabolic indices normalized in 46 and 44% patients, respectively; hepatic steatosis moderated in 56% patients; and the disturbances in hemostasis were annihilated in 67% patients.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Effect of Cardiac Myosin-Binding Protein C on Tropomyosin Regulation of Actin—Myosin Interaction Using In Vitro Motility Assay
Abstract
We studied the modulating role of cardiac myosin-binding protein C (cMyBP-C) in tropomyosin regulation of the actin—myosin interaction. The effect of cMyBP-C on the velocity of actin-tropomyosin filament sliding over cardiac and slow skeletal myosins was evaluated using in vitro motility assay. The effect of cMyBP-C on the actin-tropomyosin filaments sliding depended on the type of myosin. The regulatory effect of cMyBP-C differs for cardiac and slow skeletal myosin because of the presence of specific essential light chain (LC1sa) in slow skeletal myosin isoform.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Transmural Differences in Mechanical Properties of Isolated Subendocardial and Subepicardial Cardiomyocytes
Abstract
We studied the differences in twitch force of subendocardial and subepicardial cardiomyocytes isolated from mouse left ventricular wall at different preloads using an original single cell stretch method recently developed by us. Then, we used our mathematical models of subendocardial and subepicardial cells to predict underlying cellular mechanisms. Transmural differences in the amplitudes of active tension of subendocardial and subepicardial cardiomyocytes were revealed that could be related to the differences in cooperative end-to-end interaction between the neighboring regulatory units of the thin filament.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Selank Inhibits Ethanol-Induced Hyperlocomotion and Manifestation of Behavioral Sensitization in DBA/2 Mice
Abstract
The effect of non-benzodiazepine anxiolytics on the ethanol-induced hyperlocomotion and behavioral sensitization was assessed in male DBA/2 mice. Selank that enhances activity of the endogenous opioid system (0.3 mg/kg, intraperitoneally), similar to the nonselective opiate receptor blocker naloxone (1.0 mg/kg, intraperitoneally), prevented the development of ethanol-induced (2.0 g/kg intraperitoneally) hyperlocomotion, in contrast to σ1-receptors agonist Afobazole (1.0 mg/kg, intraperitoneally) that did not inhibit ethanol-induced behavioral stimulation. Single dose of Selank significantly blocked manifestation of motor sensitization without affecting its formation. These findings suggest that Selank can modulate the motivational effects of ethanol.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Antioxidant and Antimutagenic Metabolites in Animals with Opposite Sensitivity to Tuberculosis Mycobacteria and Mutagenic Xenobiotics
Abstract
Different sensitivity of guinea pigs and rats to Mycobacterium tuberculosis and membranotropic mutagenic xenobiotics is associated with differences in the metabolism of amino acid precursors of phospholipids. In turn, specific features of phospholipid metabolism are determined by differences in the level of sulfur-containing regulatory metabolites (methionine, taurine, and glutathione) in tissues. Taurine and methionine increase organism’s resistance to Mycobacterium tuberculosis (typical of rats), glutathione and its constituent amino acids improve resistance to the mutagenic effects of xenobiotics (typical of guinea pigs). These metabolites can be used for strengthening of natural resistance to tuberculosis and mutagenic and carcinogenic xenobiotics.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Production of Recombinant Polypeptides Containing One GA-Module and Analysis of Their Ability to Bind to Human Albumin
Abstract
Surface proteins of many bacterial species interact with human serum albumin (HSA) via a special region of amino acid sequence termed GA module. For instance, surface peptostreptococcal albumin-binding protein of anaerobic bacteria Peptostreptococcus magnus contains one HSA-binding GA-module. Protein G from group G and C Streptococcus strains isolated from humans has HSA-binding region consisting of three GA-modules. HSA-binding protein containing two GA-modules was found in strains of group G Streptococcus of animal origin. We obtained two recombinant polypeptides GA1 and GA2 congaing one GA-module each. Recombinant polypeptide with two GA-modules binds HSA with a much higher affinity than polypeptides GA1 and GA2 containing one GA-module. Polypeptide with the second GAmodule more effectively binds HSA than polypeptides with the GA-module.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Colonization by Staphylococcus aureus of Nano-Structured Fluorinated Surfaces, Formed by Different Methods of Ion-Plasma Technology
Abstract
Colonization of fluorinated surfaces produced by ion-plasma technology by Staphylococcus aureus was studied by scanning electron microscopy and surface energy analysis. It was shown that the intensity of colonization was determined by the surface relief and fluorine content. Formation of nanostructured surfaces accompanied by a sharp decrease in the surface energy prevented adhesion of Staphylococcus aureus cells to the fluorine-containing surface.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Proinflammatory Cytokines as Regulators of Vaginal Microbiota
Abstract
It was shown that IL-1β, IL-8, and IL-6 in concentrations similar to those in the vagina of healthy women stimulated the growth of normal microflora (Lactobacillus spp.) and suppressed the growth and biofilm production by S. aureus and E. coli. On the contrary, these cytokines in higher concentrations typical of vaginal dysbiosis suppressed normal microflora and stimulated the growth of opportunistic microorganisms. TGF-β1 in both doses produced a stimulating effects on study vaginal microsymbionts. It is hypothesized that pro-inflammatory cytokines serve as the molecules of interspecies communication coordinating the interactions of all components of the vaginal symbiotic system.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Association of -717A>G Polymorphism in the C-Reactive Protein Gene (CRP) with Schizotypal Personality Traits
Abstract
Associations between schizotypal traits and genes coding for inflammation markers (Creactive protein and TNF-α) were studied in 222 healthy men who completed the Schizotypal Personality Questionnaire (SPQ-74). CRP -717A>G and TNFα -308 G>A polymorphisms were genotyped. Carriers of low-active allele G of the CRP gene differed from subjects with genotype AA by a trend toward more manifest schizotypal traits in general and scores on the Interpersonal factor, which corresponds to negative syndrome in schizophrenia, and Constricted affect and Odd behavior scales. These results could be interpreted in favor of the hypothesis on a compensatory increase of CRP concentrations in subjects with abnormalities of CNS development that predispose to schizophrenia.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Structural Organization of Cerebral Basolateral Nucleus of the Amygdaloid Complex in WAG-Rij Rats with Different Genotypes by the TAQ 1A Locus of Dopamine 2 Receptor Gene (DRD2)
Abstract
Anxiety levels and structural organization of the basolateral nucleus of the amygdaloid complex were analyzed in WAG/Rij rats with genotypes A1/A1 and A2/A2 by DRD2 locus Taq 1A. Association of anxious behavior with A2/A2 genotype and the relationship between the structural organization of the nucleus and polymorphic variants of this locus are detected.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Antitumor Effects of Sorbus aucuparia L. Extract Highly Saturated with Anthocyans and Their Mechanisms
Abstract
The effects of Fructus Sorbi aucupariae extract, originally saturated with anthocyans, on the development of Lewis lung carcinoma and B-16 melanoma in C57Bl/6 mice and the efficiency of cyclophosphamide treatment were studied. Antitumor activity of the extract and potentiation of the antimetastatic activity of the cytostatic were demonstrated. Studies on melanoma B-16 model revealed an increase in the counts of stromal progenitor cells in the tumor node and their accelerated maturation after treatment with the extract. No effects towards the tumor stem and committed cells were detected.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Stimulation of Diethylnitrosamine Metabolism Reduces Its General Toxic and Hepatocarcinogenic Effects
Abstract
The general toxic and hepatocarcinogenic effects of diethylnitrosamine after stimulation of its metabolism with 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP) were studied. The hydroxylating activity of liver microsomes of C57Bl/6Mv mice towards p-nitrophenol increased more than 4-fold 3 days after injection of TCPOBOP. Injection of diethylnitrosamine 3 days after TCPOBOP caused a lesser body weight loss and decrease of food consumption in C57Bl/6Mv mice than in response to diethylnitrosamine without preinduction. Injection of diethylnitrosamine to suckling ICR mice after TCPOBOP induction of cytochrome P450 2e1 activity led to development of 2-fold lesser number of tumors and pretumorous nodes in the liver in comparison with animals injected with diethylnitrosamine without induction. These data indicated that metabolism stimulation reduced the general toxic and hepatocarcinogenic effects of diethylnitrosamine.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Evaluation of Hemodynamic Significance of Stenosis in Multiple Involvement of the Coronary Vessels by Mathematical Simulation
Abstract
We use a mathematical model of one-dimensional blood flow in a network of blood vessels for in silico evaluation of hemodynamic significance of stenoses in multivessel coronary disease. Two cases were addressed: two stenosed vessels with different diameters and with the same degree of occlusion and two consecutive stenoses in the same vessel. We show that two criteria for the evaluation of hemodynamic significance based on the degree of stenosis and based on fractional flow reserve can give contradictory indications for surgical intervention. We also show that fractional flow reserve computation originally proposed for a single stenosis should be modified in the case of multivessel stenotic disease.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
General Pathology and Pathophysiology
Pro- and Antioxidant Systems in the Lower Portion of Rat Brainstem during Hydroxybutyrate-Induced Pathological Periodic Breathing
Abstract
Activities of superoxide dismutase and catalase characterizing antioxidant status of the nervous tissue and its resistance to free radical oxidation were measured in the brainstem of rats with hydroxybutyrate-induced pathological periodic breathing. Hydroxybutyrate modified the pro- and antioxidant status in the brainstem respiratory center. It markedly inhibited catalase activity; in rats without the signs of periodic breathing, hydroxybutyrate up-regulated superoxide dismutase activity and to a lesser extent increased the resistance of the membrane structures in the medulla oblongata to induction of free radical oxidation. In rats with periodic breathing pattern, hydroxybutyrate induced more pronounced increase in the sensitivity of membrane structures in the medulla oblongata to induction of free radical oxidation.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Biophysics and Biochemistry
Effect of Cardiomyopathic Mutations in Tropomyosin on Calcium Regulation of the Actin—Myosin Interaction in Skeletal Muscle
Abstract
Tropomyosin plays an important role in the regulation of actin—myosin interaction in striated muscles. Mutations in the tropomyosin gene disrupt actin—myosin interaction and lead to myopathies and cardiomyopathies. Tropomyosin with mutations in the α-chain is expressed in both the myocardium and skeletal muscles. We studied the effect of mutations in the α-chain of tropomyosin related to hypertrophic (D175N and E180G) and dilated cardiomyopathies (E40K and E54K) on calcium regulation of the actin–myosin interaction in skeletal muscles. We analyzed the calcium-dependent sliding velocity of reconstructed thin filaments containing F-actin, troponin, and tropomyosin over myosin surface in an in vitro motility assay. Mutations D175N and E180G in tropomyosin increased the sliding velocity and its calcium sensitivity, while mutation E40K reduced both these parameters. E54K mutation increased the sliding velocity of thin filaments, but did not affect its calcium sensitivity.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Pharmacology and Toxicology
Role of PI3K, MAPK/ERK 1/2, and p38 in Production of Erythropoietic Activity by Bone Marrow Cells after Blood Loss
Abstract
The leading role in the regulation of erythropoietic activity of adherent bone marrow cells under conditions of post-hemorrhagic anemia is played by classical MAP kinase pathway (ERK pathway). Erythropoietin is not the decisive factor in the formation of erythropoietic activity of adherent cells. PI3K, MAPK/ERK 1/2, and p38-signaling proteins are not the main regulators of local production of erythropoietin after 30% loss of circulating blood volume.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Microbiology and Immunology
Evaluation In Vitro of Immunoregulatory Cytokines Secretion by Dendritic Cells in Mountain Skiers
Abstract
In vitro production of immunoregulatory cytokines (IFN-α, IL-31, TNF-β, IL-17A, IL-7, IL-1RA, IL-1α, IL-10, IL-15, IL-21, IL-22, IL-23, IL-27, and IL-9) by dendritic cell cultures was compared in ski athletes and healthy donors. Effect of prolonged intense physical exercise on secretory activity of immune cells was investigated. In both groups, secretion of IL-1RA, IL-10, IL-1α by dendritic cells was revealed, but there were significant differences in IL-1RA, IL-1α content (p<0.05) with lower level in the group of athletes. Production of IL-17A and IL-7 by dendritic cells in the group of athletes was not detected. In athletes, several proinflammatory cytokines (IFN-α, IL-31, and TNF-β) were secreted by cells in high concentrations, in contrast to the control group. In both groups, dendritic cells did not secrete IL-15, IL-21, IL-22, IL-23, IL-27, and IL-9.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Virology
Inhibition of Tobacco Ringspot Virus by the Culture Fluid of L-Lysine-α-Oxidase Producing Strain
Abstract
A producing strain of an anti-tumor and antiviral enzyme L-lysine-α-oxidase from Trichoderma was cultured using a technological device of G. K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences (Pushchino). L-lysine-α-oxidase activity in the obtained metabolite concentrate was 5.4 U/ml. We studied the effects of the concentrate of active L-lysine-α-oxidase producer on the highly infectious Tobacco ringspot virus and revealed anti-viral activity of it when enzyme concentration was at least 1.0 U/ml.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Genetics
Frequency of 3’ VNTR Polymorphism in the Dopamine Transporter Gene SLC6A3 in Humans Predisposed to Antisocial Behavior
Abstract
Predisposition to antisocial behavior can be related to the presence of certain polymorphic variants of genes encoding dopaminergic system proteins. We studied the frequencies of allele variants and genotypes of variable number tandem repeat polymorphism in 3’ untranslated region (3’ VTNR) of the dopaminergic transporter SLC6A3 gene in Caucasian men committed socially dangerous violent and non-violent crimes. Alleles with 9 and 10 repeats were most frequent in both the control group and group of men predisposed to antisocial behavior. At the same time, the 10/10 genotype was more frequently observed in the group of men prone to antisocial non-violent behavior. Hence, the presence of certain variants of 3’ VTNR polymorphism of SLC6A3 gene in men is associated with predisposition to certain forms of antisocial behavior.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Experimental Methods for Clinical Practice
Collagen-1 Membrane for Replacing the Bladder Wall
Abstract
We studied the possibility of using membrane fabricated from type 1 collagen isolated from cattle tissues (group 1) or porcine tissues (group 2) for replacement of the resected bladder wall defect in rabbits in order to retain functional volume of the organ. Satisfactory take of both types of collagen membranes with formation of competent anastomosis was observed. Histological studies revealed inflammatory process in the bladder wall at the site of contact with the implanted membrane (more pronounced in case of membranes from cattle tissues) that decreased by day 21 of the experiment. Bladder tissue ingrowth into the implant from was observed starting from day 14. The bladder capacity decreased in 7 days after surgery in both groups, presumably because of increasing tone of the organ wall resulting from surgical trauma and inflammation. In group 2, the bladder volume increased by day 14 after surgery and returned to normal by day 21, whereas in group 1 it remained below the control despite a trend to increase. These findings confirm good prospects of using collagen-1 membranes for plastic repair of the urinary bladder, the membranes from porcine collagen being more preferable.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Experimental Biology
Enzymatic Sensor Detects Some Forms of Nitric Oxide Donors Undetectable by Other Methods in Living Tissues
Abstract
Studies with the use of highly sensitive enzymatic sensor have shown the presence of various forms of nitrosyl iron complexes, including those undetectable by other methods, in living tissues. All these complexes are long-living compounds and constitute the major part of nitroso compounds in the blood, muscles, liquor, and amniotic fluid.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
Mesenchymal-Epithelial Transition in Culture of Stromal Progenitor Cells Isolated from the Liver of a Patient with Alcoholic Cirrhosis
Abstract
The cells isolated from biopsy specimen of a patient with alcoholic liver cirrhosis and cultured under standard conditions for obtaining stromal cell culture clearly diverged during early passages into two morphologically and phenotypically different subtypes: epithelial and mesenchymal. Mesenchymal cells expressed CD90 and CD44 and epithelial cells expressed CD166, CD227, and hepatocyte growth factor receptor Met. Starting from passage 6, the culture underwent spontaneous morphological changes and by passages 8-10 contained only epithelium-like cells. CD90 and CD44 expression disappeared, CD166 and CD227 expression remained unchanged, and Met expression increased. A small fraction of cells expressed GATA-4, HNF3β, HNF1α, and HNF4α. After addition of inducers of hepatogeneic differentiation, the cells started producing albumin.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Migration and Proliferative Activity of Mesenchymal Stem Cells in 3D Polylactide Scaffolds Depends on Cell Seeding Technique and Collagen Modification
Abstract
We analyzed viability of mesenchymal stem cells seeded by static and dynamic methods to highly porous fibrous 3D poly-L-lactide scaffolds with similar physical and chemical properties, but different spatial organization modified with collagen. Standard collagen coating promoted protein adsorption on the scaffold surface and improved adhesive properties of 100 μ-thick scaffolds. Modification of 600-μ scaffolds with collagen under pressure increased proliferative activity of mesenchymal stem cells seeded under static and dynamic (delivery of 100,000 cells in 10 ml medium in a perfusion system at a rate of 1 ml/min) conditions by 47 and 648%, respectively (measured after 120-h culturing by MTT test). Dynamic conditions provide more uniform distribution of collagen on scaffold fibers and promote cell penetration into 3D poly-L-lactide scaffolds with thickness >600 μ.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Analysis of Proliferation of Melanoma Cells and Mesenchymal Stem Cells in Co-Culture and Contribution of Experimental Conditions into Interpretation of the Results
Abstract
A series of experiments on co-culturing of Mel IL melanoma cells and mesenhymal stem cells showed that these cells do not influence proliferation of each other, but we observed weaker adhesion of stromal stem cells to plastic in cocultures where with melanoma cells were grown on mesenhymal stem cells feeder. Cell proliferation was also considerably influenced by experimental conditions, which should be taken into account for correct interpretation of obtained results. The principles of experiments on co-culturing of cancer and stromal cells are formulated that take into account the most important factors influencing cell behavior and minimize the probability of artifact results. It was concluded that co-culturing conditions cells significantly affect the experimental results and can be the source of conflicting conclusions on mutual influence of stromal and cancer cells in vitro.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Effect of Natural and 24-h Illumination on Mesenchymal Stem Cells
Abstract
We studied the effect 24-h illumination on quantitative and qualitative parameters of the bone marrow cells in Wistar rats. It was shown that desynchronosis reduced the release of nucleated cells from the femoral bone, while melatonin weakened this effect. The number of bone marrow mesenchymal stromal cells was resistant to circadian rhythm disturbances, while proliferation depended on glucose concentration in the medium.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Analysis of Reparative Activity of Platelet Lysate: Effect on Cell Monolayer Recovery In Vitro and Skin Wound Healing In Vivo
Abstract
Platelet lysate prepared from donor platelet concentrate and pooled according to a developed technique stimulates migration of multipotent mesenchymal stromal cells of the human adipose tissue and promotes healing of the monolayer defect in cultures of human fibroblasts and multipotent mesenchymal stromal cells in vitro in concentrations close those of fetal calf serum (5-10%). Lysate of platelets from platelet-rich rat blood plasma stimulated healing of the skin defect by promoting epithelialization and granulation tissue formation. The regenerative properties of platelet lysate in vivo increased with increasing its concentration.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Role of Tissue-Specific Stem and Progenitor Cells in the Regeneration of the Pancreas and Testicular Tissue in Diabetic Disorders
Abstract
Using the model of hypogonadism in C57Bl/6 male mice, we showed that injection of streptozotocin to newborn animals and high-fat diet induced serum IFN-γ and IL-17 elevation, glucose metabolism disturbances, insulin resistance, destructive changes of the Langerhans islets (deficit of PDX1+β cells), while the number of oligopotent β cell precursors (CD45—TER119—CD133+CD49flow) increased. Diabetes played the role of an inducer of testicular tissue inflammation (pan-hemopoietic cell infiltration, increase of IL-2, IL-17, and IL-23 content) and reproductive system disturbances in mice (decrease in free testosterone concentration, suppression of spermatogenesis, and infertility). The development of hypogonadism was paralleled by an increase in the count of spermatogonial stem cells (CD117+CD29+CD90+), multipotent mesenchymal stromal cells (CD45—CD31—CD90+CD106+), hemangiogenesis precursors (CD45—CD117+Flk1+), and epithelial cells (CD45—CD31—CD49f+CD326+).
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
The Use of Technetium-99m for Intravital Tracing of Transplanted Multipotent Stromal Cells
Abstract
We studied the possibility of in vivo tracing of multipotent mesenchymal stromal cells labeled with a radiophermaceutic preparation based on metastable isotope Technetium-99m and injected to rats with modeled traumatic brain injury. Accumulation of labeled cells occurred primarily in the liver and lungs. The cells distribution in internal organs greatly varied depending on the administration route. Cell injection into the carotid artery led to their significant accumulation in the damaged brain hemisphere, while intravenous injection was followed by diffuse cell distribution in all brain structures. Scintigraphy data were confirmed by magnetic resonance imaging and histological staining of cells. Visualization of stem cells labeled with Technetium-99m-based preparation by scintigraphy is an objective and highly informative method allowing real-time in vivo cell tracing in the body.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Proliferative Potential of Cardiomyocytes in Hypertrophic Cardiomyopathy: Correlation with Myocardial Remodeling
Abstract
Proliferating Ki-67+ cardiomyocytes were detected in the interventricular septum myocardium of adult patients with hypertrophic cardiomyopathy. In the same patients, the severity of hypertrophy and the degree of cardiomyocyte differentiation were assessed by the content of myofibrils, ultrastructural morphology, and the pattern of connexin 43-containing gap junction distribution. Adult Ki-67+ cardiomyocytes containing sarcomeric α-actin (sarc α-act+) in the sarcoplasm (diameter 23.9±6.9 μ) were detected in the myocardium of patients with hypertrophic cardiomyopathy; their relative content varied from 2 to 3084 cells per 1 million cardiomyocytes. Small early differentiating Ki-67+/sarc α-act+ cardiomyocytes with a thin cytoplasm layer (diameter 5.9±1.7 μ) constituted from 3 to 2262 cells per 1 million cardiomyocytes. These cells were found in the myocardium with the most pronounced structural changes: hypertrophy of cardiomyocytes with signs of their partial dedifferentiation.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Development of a Specific Substrate—Inhibitor Panel (Liver-on-a-Chip) for Evaluation of Cytochrome P450 Activity
Abstract
We developed a cytochrome P450 substrate—inhibitor panel for preclinical in vitro evaluation of drugs in a 3D histotypical microfluidic cell model of human liver (liver-on-a-chip technology). The concentrations of substrates and inhibitors were optimized to ensure reliable detection of the principal metabolites by HPLC—mass-spectroscopy. The selected specific substrate—inhibitor pairs, namely bupropion/2-phenyl-2-(1-piperidinyl)propane) for evaluation of CYP2B6B activity, tolbutamide/sulfaphenazole for CYP2C9, omeprazole/(+)-N-benzylnirvanol for CYP2C19, and testosterone/ketoconazole for CYP3A4, enable reliable evaluation of the drug metabolism pathway. In contrast to animal models characterized by species-specific expression profile and activity of cytochrome P450 isoforms, our in vitro model reflects the metabolism of human hepatocytes in vivo.
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)
Erratum
Erratum to: Pulsed Dendritic Cells for the Therapy of Experimental Glioma
![pages](/img/style/pages.png)
![views](/img/style/views.png)
![](/img/style/loadingSmall.gif)