Репозиторий Университета

© 2018, Media Sphera Publishing Group. All rights reserved. Over the past few decades, there has been growing concern among researchers about the health status of teachers due to their professional activities. Objective - to investigate the relationship of professional burnout (PB) in teachers towards their attitude to their own health and healthy lifestyle. Subject and methods. A total of 317 teachers (26 men and 291 women) were examined. The program encompassed a medical examination, rapid diagnosis of the stress level (L. Reeder), diagnosis of the level of emotional exhaustion (burnout) according to the questionnaire designed by V.V. Boiko, and a survey using the questionnaire that included a sociodemographic unit and questions about health attitudes. Results. Analysis of the teachers’ health self-assessment showed that 23% of women and 35% of men rated their health as good and very good; 70% of women and 62% of men regarded as satisfactory; and the remaining considered as bad. Health self-assessment decreased with higher levels of burnout. The results showed a low level of physical activity in the teachers, non-compliance with the work and rest regime, inability to manage their emotions and cope with stress, low competence in a balanced diet, and the presence of bad habits (smoking and alcohol). The number of alcohol abusers is growing in the group of women with higher PB. The women were statistically significantly ascertained to have a lower regular physical activity with a higher level of PB. Conclusion. The results show that PB has an adverse impact on health self-assessment, health attitudes, and healthy lifestyle behavior. In order to prevent PB, it is recommended that a package of preventive measures should be developed.

© 2018 Media Sphera Publishing Group.All Rights Reserved. Aim. To study the oxidative damage of biopolymers (proteins and nucleic acids) in blood of patients with type 2 diabetes mellitus (DM). Materials and methods. In the blood of 50 patients with DM and 25 patients without disorders of carbohydrate metabolism were estimated: the level of oxidized low-density lipoprotein (oxLDL) by immunochemical method, the content of SH-groups in plasma proteins, the activity of Cu, Zn-superoxide dismutase (SOD) in erythrocytes, the length of telomere in leukocyte DNA, the level of 8-hydroxy-2'-deoxy-gunosine (8-oxo-dG) in plasma and urine. Results and discussion. It is shown that in DM patients the level of oxLDL increases and the content of SH-groups in proteins and peptides of the blood plasma decreases, which indicates the development of oxidative stress. In addition, a carbonyl-dependent modification of erythrocyte SOD was detected in DM patients, as well as oxidative DNA destruction (decrease in telomere length in leukocytes and an increase in the level of 8-oxo-dG in blood plasma and urine). Conclusion. On the basis of the definition of a complex of correct indicators, a multiple oxidative modification of biopolymers of blood (proteins and DNA) was detected in patients with DM.

© 2018, Media Sfera. All rights reserved. The article describes a newly developed and tested diffractive optical element (DOE) that converts non-uniform radiation of the laser output into a homogeneous ring. The Gerchberg-Saxton algorithm is shown to be well suited for achieving annular intensity distribution. Testing this ring transducer on threshold-plasticity cornea demonstrated the reversibility of axisymmetric changes in the cornea. Atomic-Force microscopy of the area of maximum stresses in the corneal periphery showed no significant changes in the structure of the cornea when irradiated in the selected mode. Measurement of Young’s modulus of the corneal surface areas after their irradiation also revealed no changes in the elastic properties, while examination of the corneal structure demonstrated the absence of significant structural changes in irradiated samples compared with intact ones.

© 2018 Media Sphera Publishing Group.All Rights Reserved. The review presents a modern view on stress as a risk factor for the development of arterial hypertension (AH). A variety pathogenic mechanisms responsible for increase of blood pressure during stress exposure are described in detail. The importance of the sympathetic activation as a key link in the development of stress-induced AH and initiation of a cascade of pathophysiological reactions that realize their adverse effects at the level of the whole organism is underlined. Particular attention is paid to worksite AH as a variant of stress-induced hypertension due to its wide prevalence and association with an increased risk of cardiovascular complications, primarily myocardial infarction and stroke. Epidemiological data and results of recent metanalysis are presented, indicating the high significance of job strain as a risk factor for adverse cardiovascular events. The actual psychological stress reduction programs are described. Possibilities of using β-blockers in patients with stress-induced hypertension as drugs affecting the central pathogenetic trigger of this disease are considered. The advantages of using bisoprolol as a highly selective β-blocker are considered taking into account the available body of evidence for its effectiveness in patients with worksite AH, as well as its metabolic neutrality and target-organ protective properties.

© 2018, Bionika Media Ltd.. All rights reserved. Objective. To investigate the relationship of the levels of preactivated (primed) neutrophils in the peripheral blood of pregnant women with preeclampsia. Subjects and methods. The investigation enrolled 14 women with preeclampsia (a study group, Group 1), 15 women with physiological pregnancy (a control group, Group 2), and 11 non-pregnant women (to obtain normative values). Formyl peptide, Ficoll-Hypaque (1.077 and 1.119 g/ml) gradients, lucigenin, Roswell Park Memorial Institute (RPMI) 1640 medium, Hanks medium, and fetal calf serum (Sigma-Aldrich) were determined in the peripheral blood. Neutrophils were isolated from the blood samples obtained from the ulnar vein (the anticoagulant heparin 35 IU/ml) using a two-step Ficoll-Hypaque gradient. Red blood cells were destroyed by hypotonic lysis. Neutrophils in the suspensions were at least 96%. The live cells tested with trypan blue were 94%. Suspensions containing 1×106 сells/ml were prepared. Formyl-methionyl-leucyl-phenylalanine (fMLP, 2 µM) was used as a stimulant. The formation of oxygen radicals was recorded in imp/sec, by using the luminophor lucigenin (30 µM) on a Biotox-7 chemiluminometer (Russia). The maximum radical formation amplitude, the time of its achievement, and the light sum were determined for a fixed time period. Results. The cell suspensions from non-pregnant women showed a monotonic spontaneous increase in oxygen radical formation at a very low rate. The rate increased by 1.3 times in healthy pregnant women (p > 0.05). The rate of spontaneous oxygen radical generation rose sharply in pregnant women with preeclampsia. In this group, the formation of oxygen radicals reached maximum values and plateaued at 24±7 min. The spontaneous radical formation might be due to the stimulation of initially primed neutrophils as a result of their adhesion on the cell walls. To test this assumption, the standard stimulant fMLP that strongly stimulates the neutrophil generation of oxygen radicals were added to the suspensions from the women with preeclampsia. It should be noted that in both non-pregnant women and healthy pregnant women, fMLP significantly increased the level of radicals compared to the responses of neutrophils in women with preeclampsia. Conclusion. The potentiated response to formyl peptide due to spontaneous neutrophil stimulation in pregnant women with preeclampsia suggests that their peripheral blood contain primed cells. This total response may suggest that the mechanism of stimulation of neutrophils due to their adhesion on the cell wall and to fMLP stimulation is different, additive in nature, and is carried out by different processes.

© 2018, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved. Mechanical ventilation is associated with a number of complications that increase the cost of treatment and the hospital mortality rate. In 2004, the term «ventilator-induced diaphragm dysfunction» (VIDD) was proposed to explain one of the reasons for the failure of respiratory support. At present, this term is understood as a combination of atrophy and weakness of the contractile function of the diaphragm caused directly by a long-term mechanical lung ventilation. Oxidative stress, proteolysis, mitochondrial dysfunction, as well as passive overdistension of the diaphragm fibers contribute greatly to the pathogenesis of VIDD. Since 30—80% of patients in the ICU require mechanical respiratory support and even 6—8 hours of mechanical lung ventilation can contribute to the development of a significant weakness of the diaphragm, it can be concluded that the VIDD is an extremely urgent problem in most patients. Its typical clinical presentation is characterized by impaired breathing mechanics and unsuccessful attempts to switch the patient to the spontaneous breathing in the absence of other valid reasons for respiratory disorders. The sonography is the most informative and accessible diagnostic method, and preservation of spontaneous breathing activity and the use of the latest mechanical ventilation modes are considered a promising approach to prevention and correction of the disorders. The search for an optimal strategy for lung ventilation, development of diagnostic and physiotherapeutic methods, as well as the consolidation of the work of a multidisciplinary team of specialists (anesthesiologists and intensive care specialists, neurologists, pulmonologists, surgeons, etc.) can help in solving this serious problem. A review of 122 sources about the VIDD presented data on the background of the issue, the definition of the problem, etiology and pathogenesis, clinical manifestations, methods of diagnosis, the effect of drugs, prevention and therapy.

© 2018 Ima-Press Publishing House. All rights reserved. Anxiety disorders are an important biomedical problem due to the high prevalence and significant negative impact on the quality of life and the course of concomitant somatic and neurological diseases. Cognitive impairment (CI) is one of the most intensively studied aspects of pathological anxiety. Impairments in attention, executive functions, memory, cognitive deficit, as well as abnormal cognitions and metacognitions are identified in anxiety disorders. Moreover, the treatment of the latter with the most frequently used drugs (antidepressants, atypical antipsychotics, anticonvulsants, tranquilizers) does not lead to a significant improvement in cognitive functions, and often contributes to their worsening. In this connection, in addition to psychotherapy, cognitive function-improving agents play a large role in treating anxiety diseases associated with cognitive dysfunction. Ginkgo Biloba extract (EGb 761, Tanakan®) that positively affects cognitive functions, especially in the domains of memory, concentration and attention deserves special attention.

Copyright © 2018 Loppini, Gizzi, Ruiz-Baier, Cherubini, Fenton and Filippi. We numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and also assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics. We follow the recent theoretical framework from Cherubini et al. (2017), proposed in the context of general reaction-diffusion-mechanics systems emerging from multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that (i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; (ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; (iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling mechanisms using computational tests conducted with finite element methods. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The article contains the results of studying homeostasis of the cardiovascular system by the method of cardiointervalography in students with limited abilities of various programs of study at university. A psychological assessment of the attitude of students with limited abilities to their health was made. The problem of the components of the personal-adaptive potential has been studied. A study of the level of human potential of students on a separate component of “health” and in the aggregate has been conducted, as well as conclusions based on this research work have been drawn. Method: To solve the objectives set in the study, the following methods were used: the review of scientific and methodological literature, instrumental and calculated physiological research methods: variational pulsometry; mathematical analysis of the heart rate variability; calculation method for assessing adaptive capacity-adaptive capacity offered by Bayevsky; the questionnaire “Psychological features of a person’s attitude to his health”, in the framework of a study of the human potential index (health component), a questionnaire was developed based on a questionnaire for assessing the quality of life, developed at the Institute of Stress Medicine (USA) in 1993, methods-descriptive mathematical statistics and testing the hypothesis by Student’s t-test. Results: The analysis of the activity index of the sympathic regulation link-mode amplitude (AMo%) according to the standards of homeostasis, in view of variation pulsograms, is characterized in the studied groups, as moderate sympathicotonia. The AMo index in the groups is not statistically different, reflects the stabilizing effect of centralization of the heart rate control, and indicates the activation of the sympathic division of the autonomic nervous system (ANS). AMo 1 year = 40.8 ± 8.1%; AMo 2 year = 44.9 ± 4.8%; AMo 3 year = 43.9 ± 8.8% the index is in the upper limits of the norm, the index is normal only in the group of first year students. It can be stated that the body of students with limited abilities reacts with a nonspecific adaptive response to the study load, and this depends on the specifics of the diseases and functional reserves that are low in this category of students. The indicator of urgent adaptation-vagosympathetic balance (LF / HF) shows the greatest stress in the group of first-year students. The index is statistically reliably different from the LF / HF1 year = 2.074 ± 0.39 * (according to the paired Student’s t-criterion of dependent indices p ≤ 0.5) from that of students in the second LF / HF2 year = 1.174 ± 0.25 and the third LF / HF3 year = 1.308 ± 0.26 years of study, indicating an increase in sympathic influences. A decrease in the ratio of the LF / HF index in the groups of second and third year students can be interpreted as a positive effect. There was general adaptation to the educational process at the university, and the correct construction of training and health-related workloads, in accordance with the medical diagnosis, led to a balanced regulation of the sympathic and parasympathic nervous system. Conclusion: The stress level of regulatory systems is assessed by the value of the adaptation potential. The higher is the adaptive capacity of the circulatory system, the lower the values of the adaptive potential. The adaptive potential is an indicator that determines the interrelation of two opposite concepts: “health” and “disease”, morpho-functional changes. In case of illness, a shift towards disadaptation takes place.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The relationship of situational (reactive) and personal anxiety in the sample of respondents with post-trauma stress disorder (PTSD) has been considered in the article. The study found that a significant level of situational anxiety and an average level of personal anxiety is observed in respondents with post-trauma stress disorder. Method: The survey and testing of respondents was conducted on the basis of their voluntary and anonymous participation among the staff of public authorities and law enforcement bodies. Clinical, psychopathological and statistical research methods were used in this work. While conducting a psychopathological survey, the Mississippi scale (MS), military and civilian variants, the severity questionnaire for psychopathological symptoms (AFPS), and the scale for assessing the level of reactive and personal anxiety (Charles D. Spilberger, Yu. L. Khanin) were used to determine the qualitative and quantitative parameters. The levels of reactive and personal anxiety were determined on a scale: up to 30 points-low anxiety; from 31 to 45 points-moderate anxiety; 46 points or more-high anxiety. The statistical processing of research results included the calculation of the arithmetic mean value for the quantitative (M) and qualitative (P) indices and their errors (m and p). When comparing the data obtained in groups and subgroups, the Student’s t-test was used, while the correlation analysis of interrelationships-the Spearman correlation coefficient was used. The sample comprised respondents with signs that meet the diagnostic criteria for PTSD (ICD-10 \ DSM-R). Results: The manifestation of the influence of the experienced psychological trauma on the level of anxiety is: an increased heart rate; Blanchet syndrome; a nervous condition; tension of all groups of muscles; feeling a sense of guilt; a feeling of fever followed by shivers; long confusion; insomnia; migraine; uncontrollable anger. The symptoms of anxiety persist and accumulate, at the time of a stressful situation, and after its resolution, contributing to a decrease in performance, fatigue and exhaustion. In addition, the results of the study indicate that anxiety and its level plays an important role, both in clinical findings and in the pathogenesis of PTSD. At the same time, differences were found among men and women. Men with PTSD are characterized by an increase in the level of situational anxiety as the severity of the disorder increases. Women are characterized by a moderate level of situational anxiety, regardless of the severity of the disorder. For both male and female subjects, high indices of personal anxiety are more significant than situational in the development of PTSD of different severity levels. Conclusion: Anxiety and its level, plays an important role both in clinical findings and in the pathogenesis of PTSD. At the same time, differences were found among men and women. Men with PTSD are characterized by an increase in the level of situational anxiety as the severity of the disorder increases. Women are characterized by a moderate level of situational anxiety, regardless of the severity of the disorder. High indices of personal anxiety are more significant for both male and female subjects than situational one in the development of PTSD of different severity levels. The level of personal anxiety in men increased as the severity of PTSD increased. In women, the high level of anxiety increased with increasing severity of the disorder and stabilized with severe PTSD. Most women and men with PTSD are characterized by a high level of personal anxiety. Moreover, the prevalence of women with a high level of personal anxiety in comparison with men is essential with a mild severity of the disorder. With a moderate degree of the disorder, the differences in the proportion of men and women with a high level of personal anxiety are practically insignificant, and in case of a severe degree of the disorder, their proportion levels off, reaching 100%, both among men and women.

© Bionika Media Ltd. Objective. To determine the expression level of the genes encoding the paraoxonase family enzymes (PON1, PON2, and PON3) in the placentas of women with uncomplicated pregnancy and in the development of preeclampsia Materials and methods. The investigation enrolled 26 pregnant women aged 24 to 35 years, including 14 women with normal pregnancy and 12 with preeclampsia. The expression of the PON1, PON2, and PON3 genes was analyzed by real-time PCR using the primers specific to these genes. Results. Women whose pregnancy was complicated by preeclampsia showed a significant decrease in the placental expression of the PON2 gene. The lowest PON2 gene expression was found in the placentas of women with severe preeclampsia. There were no significant differences in the placental expression level of the PON1 and PON3 genes in women with preeclampsia compared to healthy women. Conclusion. In women with preeclampsia, the placental PON2 gene expression decreases; however, the expression level of the PON1 and PON3 genes does not differ from that of the PON1 and PON3 genes in the placentas of patients with physiological pregnancy. The placental expression of the PON2 gene depends on the severity of preeclampsia; is lower in severe preeclampsia than in moderate preeclampsia.

© 2017, Springer Science+Business Media, LLC. Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.

© 2018 Izdatel'stvo Meditsina. All rights reserved. We have studied the adaptogenic properties of Kardecaim phytopreparation based on dry extracts derived from Inula helenium L., Zingiber officinale Roscoe, Elletaria cardamomum (L.) Maton., and Caragaha spinose (L.) Wall, ex Homem, which contain phenolic compounds and terpenoids. A course of preventive administration of Kardecaim to white rats in a dose of 100 mg/kg for 7 days before the induction of acute emotional stress produced stress-protective effect by preventing the development of catabolic signs of Selye's triad in animal inner organs, including the thymus involution (40% lower than in control); degree of hemorrhagic and ulcerative defects in the stomach mucosa (5 times less than reference gastroprotector effect), and somewhat less pronounced effect on the stress-induced hypertrophy of adrenal glands, yet comparable to the effect of reference preparation (eleutherococcus extract). It was shown that the increase in the resistance to stress under the action of Kardecaim was due to the activation of synthesis of heat shock proteins (Hsp). The Hsp-70 content in the thymus of white rats undergoing emotional stress was 56% higher than in the control. The introduction of Kardecaim to intact animals had no effect on the basal level of Hsp-70. It was established that the expression of Hsp under the drug action was not connected with NO system, since the administration of Kardecaim on the background of stress impact was followed by a decrease in the NO metabolite yield.

© Springer Science+Business Media New York 2016. A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

© 2018 Bentham Science Publishers. Urotensin II (UT II) is an important factor of cellular homeostasis. This regulatory peptide is involved in the pathophysiology of many disorders. For example, it plays an important role in the pathogenesis of acute and chronic diseases, stressful and adaptive reactions of the body, in the development of cardiovascular pathologies, metabolic syndrome, inflammation, liver cirrhosis, renal failure, diabetic nephropathy, reproductive dysfunction, progression of psychosomatic, psychoendocrinal and psychiatric disorders. In this concern, the involvement of UT II in the pathophysiology of many processes determines the perspectives for the development of blockers of urotensin receptors for the treatment of the aforementioned diseases. It is important that even today this kind of perspective is feasible due to the synthesis of a series of GPR14 blockers. The objective of this review is to discuss current molecular mechanisms of biological activity, regulatory functions of UT II, its role in the pathogenesis of different nosologies, as well as analysis of the possible routes of exposure to GPR14 as potential therapeutic targets.

A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.

A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.

Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.