On the application of different surfactant types to measure the carbonate’s adsorption density: a parametric study
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01.12.2021 |
Peng X.
Aljeboree A.M.
Timoshin A.
Nassabeh S.M.M.
Davarpanah A.
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Carbonates and Evaporites |
10.1007/s13146-021-00728-3 |
0 |
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Due to the cost efficiency and environmentally friendly surfactant features in enhanced oil recovery techniques, the appropriate designation of surfactant flooding should be considered. It is essential to evaluate the crucial factors that affect surfactant adsorption on rock surfaces to eliminate the total economic losses of surfactant retention and adsorption in porous media. In this paper, the considerable influence of temperature, different surfactant concentrations, and polymer addition were experimentally investigated for dolomite minerals extracted from Pabdeh formation. According to this study, higher adsorption density has occurred at lower temperatures, which implies lower kinetic energy between the surfactant molecules. For 25 ℃, the adsorption density is about 41 mg/g, and it has the lowest value of 100 ℃. It is about 17 mg/g. By the increase of surfactant concentration for different time steps, adsorption density has been increased. For the surfactant concentration of 5 Wt. %, the adsorption density is about 42 mg/g; however, it is for 0.15 Wt. % of surfactant concentration, the adsorption density is about 1 mg/g. Moreover, due to the higher stability of polymers, adsorption density has been decreased by the addition of polymer. The stopping time for each surfactant concentration is about 6.5 h for the surfactant concentration of 5 Wt. %. Consequently, the critical micelle concentration point is about 3.5 Wt. %, 4 Wt. %, and 5 Wt. % for linear alkylbenzene sulfonic acid, cetyl trimethyl ammonium bromide, and Triton X-100, respectively. This change in the conductivity is related to the start of the micelling process by increasing surfactant concentration.
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Alterations in Blood Metabolic Parameters of Immature Mice After Subchronic Exposure to Cobalt Chloride
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01.02.2021 |
Vladov I.
Petrova E.
Pavlova E.
Tinkov A.A.
Ajsuvakova O.P.
Skalny A.V.
Gluhcheva Y.
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Biological Trace Element Research |
10.1007/s12011-020-02161-4 |
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© 2020, Springer Science+Business Media, LLC, part of Springer Nature. The wide use of cobalt (Co) in food, industry, and medical devices requires full elucidation of its biological effects on tissues and organs. The aim was to assess serum metabolic alterations in immature mice after subchronic exposure to CoCl2. Pregnant ICR mice were subjected to a daily dose of 75 mg cobalt chloride/kg body weight (CoCl2x6H2O) 2–3 days before they gave birth, and treatment continued until days 25 and 30 after delivery. The compound was dissolved in and obtained with regular tap water. ICP-DRC-MS analysis showed significantly elevated serum Co2+ and diverse alterations in metabolic parameters of 25- and 30-day-old pups after exposure to CoCl2. Cholesterol and urea levels were significantly elevated in day 25 mice while HDL-C and LDL-C were reduced. In day 30, Co-exposed mice LDL-C and triglycerides were significantly increased while the total cholesterol level remained unchanged. Alkaline phosphatase was significantly reduced in day 25 Co-exposed mice. Blood glucose level of Co-exposed mice remained close to the untreated controls. Total protein content was slightly increased in day 30 mice. Co-exposure reduced albumin content and albumin/globulin ratio but increased significantly globulin content. Co administration showed strong correlation with cholesterol, urea, and HDL-C in both day 25 and 30 mice. Inverse correlation was found with alkaline phosphatase and albumin for day 25 and with triglycerides, globulin, and total protein content in day 30 Co-exposed mice. Subchronic CoCl2 exposure of immature mice induced significant changes in key metabolic parameters suggesting possible further disturbances in energy metabolism, osteogenesis, and reproduction.
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Alterations in Blood Metabolic Parameters of Immature Mice After Subchronic Exposure to Cobalt Chloride
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01.02.2021 |
Vladov I.
Petrova E.
Pavlova E.
Tinkov A.A.
Ajsuvakova O.P.
Skalny A.V.
Gluhcheva Y.
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Biological Trace Element Research |
10.1007/s12011-020-02161-4 |
0 |
Ссылка
© 2020, Springer Science+Business Media, LLC, part of Springer Nature. The wide use of cobalt (Co) in food, industry, and medical devices requires full elucidation of its biological effects on tissues and organs. The aim was to assess serum metabolic alterations in immature mice after subchronic exposure to CoCl2. Pregnant ICR mice were subjected to a daily dose of 75 mg cobalt chloride/kg body weight (CoCl2x6H2O) 2–3 days before they gave birth, and treatment continued until days 25 and 30 after delivery. The compound was dissolved in and obtained with regular tap water. ICP-DRC-MS analysis showed significantly elevated serum Co2+ and diverse alterations in metabolic parameters of 25- and 30-day-old pups after exposure to CoCl2. Cholesterol and urea levels were significantly elevated in day 25 mice while HDL-C and LDL-C were reduced. In day 30, Co-exposed mice LDL-C and triglycerides were significantly increased while the total cholesterol level remained unchanged. Alkaline phosphatase was significantly reduced in day 25 Co-exposed mice. Blood glucose level of Co-exposed mice remained close to the untreated controls. Total protein content was slightly increased in day 30 mice. Co-exposure reduced albumin content and albumin/globulin ratio but increased significantly globulin content. Co administration showed strong correlation with cholesterol, urea, and HDL-C in both day 25 and 30 mice. Inverse correlation was found with alkaline phosphatase and albumin for day 25 and with triglycerides, globulin, and total protein content in day 30 Co-exposed mice. Subchronic CoCl2 exposure of immature mice induced significant changes in key metabolic parameters suggesting possible further disturbances in energy metabolism, osteogenesis, and reproduction.
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Effects of acute and chronic arecoline in adult zebrafish: Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia
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10.01.2021 |
Serikuly N.
Alpyshov E.T.
Wang D.M.
Wang J.T.
Yang L.E.
Hu G.J.
Yan D.N.
Demin K.A.
Kolesnikova T.O.
Galstyan D.
Amstislavskaya T.G.
Babashev A.M.
Mor M.S.
Efimova E.V.
Gainetdinov R.R.
Strekalova T.
de Abreu M.S.
Song C.
Kalueff A.V.
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Progress in Neuro-Psychopharmacology and Biological Psychiatry |
10.1016/j.pnpbp.2020.109977 |
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© 2020 Elsevier Inc. Arecoline is a naturally occurring psychoactive alkaloid with partial agonism at nicotinic and muscarinic acetylcholine receptors. Arecoline consumption is widespread, making it the fourth (after alcohol, nicotine and caffeine) most used substance by humans. However, the mechanisms of acute and chronic action of arecoline in-vivo remain poorly understood. Animal models are a valuable tool for CNS disease modeling and drug screening. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a promising novel model organism for neuroscience research. Here, we assessed the effects of acute and chronic arecoline on adult zebrafish behavior and physiology. Overall, acute and chronic arecoline treatments produced overt anxiolytic-like behavior (without affecting general locomotor activity and whole-body cortisol levels), with similar effects also caused by areca nut water extracts. Acute arecoline at 10 mg/L disrupted shoaling, increased social preference, elevated brain norepinephrine and serotonin levels and reduced serotonin turnover. Acute arecoline also upregulated early protooncogenes c-fos and c-jun in the brain, whereas chronic treatment with 1 mg/L elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). Finally, acute 2-h discontinuation of chronic arecoline treatment evoked withdrawal-like anxiogenic behavior in zebrafish. In general, these findings support high sensitivity of zebrafish screens to arecoline and related compounds, and reinforce the growing utility of zebrafish for probing molecular mechanisms of CNS drugs. Our study also suggests that novel anxiolytic drugs can eventually be developed based on arecoline-like molecules, whose integrative mechanisms of CNS action may involve monoaminergic and neuro-immune modulation.
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Potential of the zebrafish model for the forensic toxicology screening of NPS: A comparative study of the effects of APINAC and methiopropamine on the behavior of zebrafish larvae and mice
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01.05.2020 |
Morbiato E.
Bilel S.
Tirri M.
Arfè R.
Fantinati A.
Savchuk S.
Appolonova S.
Frisoni P.
Tagliaro F.
Neri M.
Grignolio S.
Bertolucci C.
Marti M.
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NeuroToxicology |
10.1016/j.neuro.2020.02.003 |
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© 2020 The Authors The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.
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Potential of the zebrafish model for the forensic toxicology screening of NPS: A comparative study of the effects of APINAC and methiopropamine on the behavior of zebrafish larvae and mice
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01.05.2020 |
Morbiato E.
Bilel S.
Tirri M.
Arfè R.
Fantinati A.
Savchuk S.
Appolonova S.
Frisoni P.
Tagliaro F.
Neri M.
Grignolio S.
Bertolucci C.
Marti M.
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NeuroToxicology |
10.1016/j.neuro.2020.02.003 |
0 |
Ссылка
© 2020 The Authors The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.
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The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice
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01.04.2020 |
Gluhcheva Y.
Pavlova E.
Petrova E.
Tinkov A.
Ajsuvakova O.
Skalnaya M.
Vladov I.
Skalny A.
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Biological Trace Element Research |
10.1007/s12011-019-01790-8 |
0 |
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© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2–3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.
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The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice
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01.04.2020 |
Gluhcheva Y.
Pavlova E.
Petrova E.
Tinkov A.
Ajsuvakova O.
Skalnaya M.
Vladov I.
Skalny A.
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Biological Trace Element Research |
10.1007/s12011-019-01790-8 |
0 |
Ссылка
© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2–3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.
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Prefrontal cortex inflammation and liver pathologies accompany cognitive and motor deficits following Western diet consumption in non-obese female mice
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15.01.2020 |
Veniaminova E.
Oplatchikova M.
Bettendorff L.
Kotenkova E.
Lysko A.
Vasilevskaya E.
Kalueff A.
Fedulova L.
Umriukhin A.
Lesch K.
Anthony D.
Strekalova T.
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Life Sciences |
10.1016/j.lfs.2019.117163 |
1 |
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© 2019 Aims: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. Main methods: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. Key findings: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. Significance: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.
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Prefrontal cortex inflammation and liver pathologies accompany cognitive and motor deficits following Western diet consumption in non-obese female mice
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15.01.2020 |
Veniaminova E.
Oplatchikova M.
Bettendorff L.
Kotenkova E.
Lysko A.
Vasilevskaya E.
Kalueff A.
Fedulova L.
Umriukhin A.
Lesch K.
Anthony D.
Strekalova T.
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Life Sciences |
10.1016/j.lfs.2019.117163 |
1 |
Ссылка
© 2019 Aims: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. Main methods: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. Key findings: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. Significance: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.
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Dataset for determining rational taxation value with incompatible criteria of economic efficiency and equity
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01.10.2019 |
Akhmetshin E.
Plaskova N.
Iusupova I.
Prodanova N.
Leontyev A.
Vasilev V.
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Data in Brief |
10.1016/j.dib.2019.104532 |
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© 2019 The Authors This article is essentially a dataset necessary for analysing the taxation. The data analysis has allowed to determine the optimal taxation model, when the criteria of economic efficiency and equity are incompatible. The dataset has allowed the use of the method of successive concessions in tax optimization. The practical significance of the dataset lies in the ability to simultaneously improve the efficiency and equity in taxation. The dataset was obtained by using the method of expert estimates. A group of experts was asked to rank the taxes established by the Tax Code of the Russian Federation, in descending order of importance. Only strict rankings were allowed. The consistency of expert opinion was evaluated using the Kendall coefficient of concordance. The data set was supplemented with the expert ranking data of the basic principles of taxation, such as the principle of equity; the principle of certainty and accuracy of taxes; the principle of ease of tax collection for taxpayers; the principle of efficiency; the principle of commitment. The dataset can be used in the future to determine a rational amount of taxation depending on the established criteria.
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Thiamine and benfotiamine counteract ultrasound-induced aggression, normalize AMPA receptor expression and plasticity markers, and reduce oxidative stress in mice
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15.09.2019 |
Gorlova A.
Pavlov D.
Anthony D.
Ponomarev E.
Sambon M.
Proshin A.
Shafarevich I.
Babaevskaya D.
Lesсh K.
Bettendorff L.
Strekalova T.
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Neuropharmacology |
10.1016/j.neuropharm.2019.02.025 |
1 |
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© 2019 Elsevier Ltd The negative societal impacts associated with the increasing prevalence of violence and aggression is increasing, and, with this rise, is the need to understand the molecular and cellular changes that underpin ultrasound-induced aggressive behavior. In mice, stress-induced aggression is known to alter AMPA receptor subunit expression, plasticity markers, and oxidative stress within the brain. Here, we induced aggression in BALB/c mice using chronic ultrasound exposure and examined the impact of the psychoactive anti-oxidant compounds thiamine (vitamin B1), and its derivative benfotiamine, on AMPA receptor subunit expression, established plasticity markers, and oxidative stress. The administration of thiamine or benfotiamine (200 mg/kg/day) in drinking water decreased aggressive behavior following 3-weeks of ultrasound exposure and benfotiamine, reduced floating behavior in the swim test. The vehicle-treated ultrasound-exposed mice exhibited increases in protein carbonyl and total glutathione, altered AMPA receptor subunits expression, and decreased expression of plasticity markers. These ultrasound-induced effects were ameliorated by thiamine and benfotiamine treatment; in particular both antioxidants were able to reverse ultrasound-induced changes in GluA1 and GluA2 subunit expression, and, within the prefrontal cortex, significantly reversed the changes in protein carbonyl and polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression levels. Benfotiamine was usually more efficacious than thiamine. Thus, the thiamine compounds were able to counteract ultrasound-induced aggression, which was accompanied by the normalization of markers that have been showed to be associated with ultrasound-induced aggression. These commonly used, orally-active compounds may have considerable potential for use in the control of aggression within the community. This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.
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Activated protein C induces suppression and regression of choroidal neovascularization– A murine model
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01.09.2019 |
Livnat T.
Weinberger Y.
Budnik I.
Deitch I.
Dahbash M.
Sella R.
Dardik R.
Kenet G.
Nisgav Y.
Weinberger D.
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Experimental Eye Research |
10.1016/j.exer.2019.107695 |
0 |
Ссылка
© 2019 Elsevier Ltd Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC. CNV was induced by laser photocoagulation in C57BL/6J mice. APC was injected intravitreally immediately or 7 days after CNV induction. Neovascularization was evaluated on RPE-choroidal flatmounts using FITC-dextran perfusion and CD31 immunofluorescence. CNV leakage was measured by fluorescein angiography (FA). The ability of APC to stabilize the RPE barrier was evaluated in-vitro by dextran permeability and zonula occludens 1 (ZO1) immunostaining. Tie2 blocking was induced in-vivo by intraperitoneal injection of Tie2 kinase inhibitor and in-vitro by incubation with anti Tie2 antibodies. APC treatment dramatically inhibited the generation of newly formed CNV leakage sites and reversed leakage in 85% of the pre-existing CNV leaking sites. In RPE cell culture, APC induced translocation of ZO1 to the cell membrane, accompanied by reduction in permeability of the monolayer. Inhibition of Tie2 significantly decreased APC protective activities in both the mouse model and the RPE cell culture. Our results show that APC treatment significantly inhibits the leakage and growth of newly formed, as well as pre-existing CNV, and its protective activities are partially mediated via the Tie2 receptor. The data suggest that APC should be further investigated as a possible effective treatment for CNV.
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The Analysis of Actual Approaches in Evaluating Efficiency of Medical Care of Female Patients with Habitual Miscarriage
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01.07.2018 |
Vartanian E.
Gridnev O.
Belostotsky A.
Pesennikova E.
Gadaborshev M.
Kuchitz S.
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Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsiny |
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The prevalence of habitual miscarriage varies depending on territories of the Russian Federation and other countries. The rate of premature delivery in the Moscow Zelenograd administrative okrug in 2013-2015 in average made up to 4.5%-4.7%. The percentage of habitual miscarriage made up to 3.6% that is a rather low indicator as compared with other Moscow okrugs and national average indices. The article considers three-level model of evaluation of medical, economic and social efficiency of obstetric gynecologic care support of population at the out-patient stage.
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Activation of mTORC1 in chondrocytes does not affect proliferation or differentiation, but causes the resting zone of the growth plate to become disordered
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01.06.2018 |
Newton P.
Xie M.
Medvedeva E.
Sävendahl L.
Chagin A.
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Bone Reports |
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4 |
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© 2018 The Authors There are several pitfalls associated with research based on transgenic mice. Here, we describe our interpretation and analysis of mTORC1 activation in growth plate chondrocytes and compare these to a recent publication (Yan et al., Nature Communications 2016, 7:11151). Both laboratories employed TSC1-floxed mice crossed with collagen type 2-driven Cre (Col2-Cre), but drew substantially different conclusions. It was reported that activation of mechanistic target of rapamycin complex 1 (mTORC1) via Tsc1 ablation promotes the hypertrophy of growth plate chondrocytes, whereas we observe only disorganization in the resting zone, with no effect on chondrocyte hypertrophy or proliferation. Here, we present our data and discuss the differences in comparison to the earlier phenotypic characterization of TSC1 ablation in cartilage. Importantly, we detect Col2-Cre activity in non-cartilaginous tissues (including the brain) and discuss it in relation to other studies reporting non-cartilaginous expression of collagen alpha(1) II. Altogether, we conclude that mouse phenotypes following genetic ablation using Col2-Cre should be interpreted with care. We also conclude that activation of mTORC1 by TSC1 ablation in postnatal chondrocytes with inducible Col2-Cre (Col2-CreERt) leads to disorganization of the resting zone but causes no changes in chondrocyte proliferation or differentiation.
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Dose–Response Effect of Antibodies to S100 Protein and Cannabinoid Receptor Type 1 in Released-Active Form in the Light–Dark Test in Mice
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01.04.2018 |
Kardash E.
Ertuzun I.
Khakimova G.
Kolyadin A.
Tarasov S.
Wagner S.
Andriambeloson E.
Ivashkin V.
Epstein O.
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Dose-Response |
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1 |
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© The Author(s) 2018. Earlier studies have shown that combination of antibodies to S100 protein and to cannabinoid receptor type 1 in released-active form (Brizantin) may possess anxiolytic properties and decrease nicotine dependence. Released-active form of antibodies is a novel approach that permits to modify natural functions of the target molecule (antigen) under investigation. The aim of the present study was to evaluate the anxiolytic-like effect of Brizantin in the light–dark test in mice, according to its ability to influence the number of entries into the lit compartment and the total time spent there. Three doses of Brizantin (2.5, 5, and 10 mL/kg) were compared with diazepam (1 mg/kg), placebo, and vehicle control. Anxiolytic-like effect of the tested drug was shown to be dose dependent, with an increasing trend from 2.5 to 10 mL/kg. Brizantin in its highest dose significantly increased studied behavioral parameters, although its effect was less pronounced than that of the reference drug diazepam (1 mg/kg).
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Increased fear learning, spatial learning as well as neophobia in Rgs2 <sup>−/−</sup> mice
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01.04.2018 |
Raab A.
Popp S.
Lesch K.
Lohse M.
Fischer M.
Deckert J.
Hommers L.
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Genes, Brain and Behavior |
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© 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society Anxiety disorders result from a complex interplay of genetic and environmental factors such as stress. On the level of cellular signaling, regulator of G protein signaling 2 (Rgs2) has been implicated in human and rodent anxiety. However, there is limited knowledge about the role of Rgs2 in fear learning and reactivity to stress. In this study, Rgs2 −/− mice showed increased fear learning, male mice displayed increased contextual and cued fear learning, while females showed selectively enhanced cued fear learning. Male Rgs2 −/− mice displayed increased long-term-contextual fear memory, but increased cued fear extinction. Learning in spatial non-aversive paradigms was also increased in Rgs2 −/− mice. Female, but not male mice show increased spatial learning in the Barnes maze, while male mice showed enhanced place preference in the IntelliCage, rendering enhanced cognitive function non-specific for aversive stimuli. Consistent with the previous results, Rgs2 deletion resulted in increased innate anxiety, including neophobic behavior expressed as hypolocomotion, in three different tests based on the approach-avoidance conflict. Acute electric foot shock stress provoked hypolocomotion in several exploration-based tests, suggesting fear generalization in both genotypes. Rgs2 deletion was associated with reduced monoaminergic neurotransmitter levels in the hippocampus and prefrontal cortex and disturbed corresponding GPCR expression of the adrenergic, serotonergic, dopaminergic and neuropeptide Y system. Taken together, Rgs2 deletion promotes improved cognitive function as well as increased anxiety-like behavior, but has no effect on acute stress reactivity. These effects may be related to the observed disruption of the monoaminergic systems.
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Cost-effectiveness of HLA-B*5701 prospective genetic screening of hypersensitivity to abacavir
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01.02.2018 |
Kubaeva M.
Gushchina J.
Loskutova E.
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Asian Journal of Pharmaceutical and Clinical Research |
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© 2018 The Authors. Objective: This study was conducted to evaluate the use of genetic tests, before prescribing drugs to reduce not only the level of side effects but also the costs associated with changing therapy. In this paper, the authors analyze the economic efficiency of HLA*5701 prospective screening of hypersensitivity to abacavir (ABC) in the treatment of HIV-infected patients. Methods: A retrospective study was conducted among HIV-infected patients taking first-line antiretroviral therapy and further, based on the results obtained with the ABC-hypersensitivity reactions, analyzed the costs that affect on healthcare system. Results: In the study group of HIV-infected patients, most of the cases belonged to a young, socially active part of the population. Among the study population of patients (n=637), 171 patients were assigned ABC-containing antiretroviral therapy. An increase in costs was found in 67% of cases when ABC-containing first-line therapy was replaced due to the occurrence of undesirable reactions. Conclusion: The results show that, using this screening, we could reduce the costs associated with replacement therapy.
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The role of neurosteroids metabolism in anticompulsive effect of pyrazole[c]pyridine derivative gizh-72
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01.01.2018 |
Kudryashov N.
Kalinina T.
Kasabov K.
Shimshirt A.
Volkova A.
Zhmurenko L.
Voronina T.
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Eksperimental'naya i Klinicheskaya Farmakologiya |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. There were studied the impact of selective antagonist of the mitochondrial translocator protein (TSPO 18 kDa) PK11195 (N-butan-2-yl-l-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide; 1 or 3 mg/kg, i.p.) and 5α-reductase inhibitor finasteride (1.25; 2.5; 5 mg/kg, i.p.) on anticonvulsive effect of pyrazole[c]pyridine derivative GIZH-72 (4,6-dimethyl-2-(4-chlorophenyl)-2,3-dihydro-l//-pyrazolo[4,3-c]pyridin-3-one chloralhydrate, 20 mg/kg, i.p.) in marble burying test in C57BL/6 mice. It is established that PK11195 (1 or 3 mg/kg, i.p.) had no effects on both compulsive behavior of mice and anticompulsive effect of GIZH-72 (20 mg/kg, i.p.). Finasteride (2.5 or 5.0 mg/kg) decreased of compulsive behavior in the dose-dependent manner in C57BL/6 mice. Pretreatment with finasteride (2.5 or 5.0 mg/kg, i.p.) led to completely reduction of anticompulsive effect of GIZH-72 (20 mg/kg, i.p.). Thus, anticompulsive effect of GIZH-72 may depend on activity of 5α-reductase, but not TSPO 18 kDa.
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The estimated efficiency of pneumococcal vaccination in able-bodied men
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01.01.2018 |
Briko N.
Batyrshina L.
Briko A.
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Profilakticheskaya Meditsina |
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© 2018 Media Sphera Publishing Group. All rights reserved. Objective - to evaluate the possible epidemiological and economic efficiency of pneumococcal vaccination in men with different chronic diseases. Material and methods. A prognostic (Markov) model was constructed based on the data available in the literature. The estimated efficiency of pneumococcal vaccination in reducing mortality, preventable diseases, and economic damage over a 5-year period was evaluated in able-bodied men. According to official statistics, the group at high risk for pneumonia in the Russian Federation includes 21,575,887 able-bodied men. The sources of data on the cost of the disease were governmental tariffs in the compulsory health insurance system in 2016 and those of vaccination cost were the results of competitive bidding for the procurement of 13-valent pneumococcal conjugate vaccine (PCV13). Results. The results of extrapolation of data from Russian and foreign studies in patients with chronic respiratory diseases, circulatory diseases, or diabetes mellitus showed a significant reduction in the risk of complications due to the underlying disease (RR=0.58; p<0.05), the number of hospitalizations (RR=0.02; p<0.05), and expected postvaccination mortality. The cost of vaccination in the assessed patient group was 25,869.5 million rubles. The use of PCV13 significantly reduces the number of exacerbations and, accordingly, hospitalizations, which saves about 14,359.9 million rubles in each subsequent year after vaccination. Thus, the total budget savings can reach 2,850.3 million rubles just during 2 years. A single dose of PCV13 will save at least 61,702 lives over 5 years. Conclusion. The results of this investigation suggest that pneumococcal vaccination has high epidemiological and clinical efficiency in able-bodied men with chronic diseases. This intervention reduces morbidity rates, the number of exacerbations and hospitalizations, as well as deaths in the vaccinated group, and it is a cost-effective investment in public health service.
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