Concorrência tributária entre regiões da Rússia e seus indicadores

The article focuses on approaches to assessing the competitive advantages of regions of Russia in the area of taxation, the main approaches to the definition of tax competition at the present stage used in the scientific literature, are considered; emphasis on the influence of internal tax competition on social and economic development of the regions; the possibilities of using a number of quantitative and qualitative indicators to assess the competitive advantages of the regions in the area of taxation are summarized; ranking of the regions of Russia by using tax authorities to provide tax benefits of corporate income tax paid to the budget of the Russian Federation constituent, was performed; the conclusion about the relationship of investment activity and the availability of competitive advantages in the area of taxation was made; the development problems of the regional competitive advantages in the area of taxation and prospects for their solution are described.El artículo se centra en los enfoques para evaluar las ventajas competitivas de las regiones de Rusia en el área de la tributación, se consideran los principales enfoques para la definición de competencia fiscal en la etapa actual utilizados en la literatura científica; énfasis en la influencia de la competencia fiscal interna sobre el desarrollo social y económico de las regiones; se resumen las posibilidades de utilizar una serie de indicadores cuantitativos y cualitativos para evaluar las ventajas competitivas de las regiones en el área de la tributación; clasificación de las regiones de Rusia mediante el uso de las autoridades fiscales para proporcionar los beneficios fiscales del impuesto sobre la renta corporativo pagado al presupuesto del constituyente de la Federación de Rusia; se llegó a la conclusión sobre la relación de la actividad inversora y la disponibilidad de ventajas competitivas en el área de tributación; se describen los problemas de desarrollo de las ventajas competitivas regionales en el área de impuestos y las perspectivas para su solución. O artigo enfoca as abordagens para avaliar as vantagens competitivas das regiões russas na área de tributação, considerando as principais abordagens para a definição de concorrência tributária no atual estágio utilizado na literatura científica; ênfase na influência da concorrência fiscal interna no desenvolvimento social e econômico das regiões; as possibilidades de utilizar uma série de indicadores quantitativos e qualitativos para avaliar as vantagens competitivas das regiões na área de tributação são resumidas; classificação das regiões da Rússia, usando as autoridades fiscais para fornecer os benefíciosfiscais do imposto de renda corporativo pago ao orçamento do constituinte da Federação Russa; chegouse à conclusão sobre a relação entre a atividade de investimento e a disponibilidade de vantagens competitivas na área de tributação; São descritos os problemas de desenvolvimento de vantagenscompetitivas regionais na área tributária e as perspectivas de sua solução

Designing in vitro Blood-Brain Barrier Models Reproducing Alterations in Brain Aging

Blood-brain barrier (BBB) modeling in vitro is a huge area of research covering study of intercellular communications and development of BBB, establishment of specific properties that provide controlled permeability of the barrier. Current approaches in designing new BBB models include development of new (bio) scaffolds supporting barriergenesis/angiogenesis and BBB integrity; use of methods enabling modulation of BBB permeability; application of modern analytical techniques for screening the transfer of metabolites, bio-macromolecules, selected drug candidates and drug delivery systems; establishment of 3D models; application of microfluidic technologies; reconstruction of microphysiological systems with the barrier constituents. Acceptance of idea that BBB in vitro models should resemble real functional activity of the barrier in different periods of ontogenesis and in different (patho) physiological conditions leads to proposal that establishment of BBB in vitro model with alterations specific for aging brain is one of current challenges in neurosciences and bioengineering. Vascular dysfunction in the aging brain often associates with leaky BBB, alterations in perivascular microenvironment, neuroinflammation, perturbed neuronal and astroglial activity within the neurovascular unit, impairments in neurogenic niches where microvascular scaffold plays a key regulatory role. The review article is focused on aging-related alterations in BBB and current approaches to development of “aging” BBB models in vitro

Plasticity of Adipose Tissue-Derived Stem Cells and Regulation of Angiogenesis

Adipose tissue is recognized as an important organ with metabolic, regulatory, and plastic roles. Adipose tissue-derived stem cells (ASCs) with self-renewal properties localize in the stromal vascular fraction (SVF) being present in a vascular niche, thereby, contributing to local regulation of angiogenesis and vessel remodeling. In the past decades, ASCs have attracted much attention from biologists and bioengineers, particularly, because of their multilineage differentiation potential, strong proliferation, and migration abilities in vitro and high resistance to oxidative stress and senescence. Current data suggest that the SVF serves as an important source of endothelial progenitors, endothelial cells, and pericytes, thereby, contributing to vessel remodeling and growth. In addition, ASCs demonstrate intriguing metabolic and interlineage plasticity, which makes them good candidates for creating regenerative therapeutic protocols, in vitro tissue models and microphysiological systems, and tissue-on-chip devices for diagnostic and regeneration-supporting purposes. This review covers recent achievements in understanding the metabolic activity within the SVF niches (lactate and NAD+ metabolism), which is critical for maintaining the pool of ASCs, and discloses their pro-angiogenic potential, particularly, in the complex therapy of cardiovascular and cerebrovascular diseases

Аберрантный ангиогенез в ткани головного мозга при экспериментальной болезни Альцгеймера

The aim was to study the molecular mechanisms of the violation of the structural and functional integrity ofthe blood-brain barrier in chronic neurodegeneration of the Alzheimer’s type associated with the development of cerebral angiopathy.Materials and methods. The transgenic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon,PSEN1 * M146L * L286V) 6799Vas group which includes 9 months aged males. The control group included C57BL / 6 x SJL mice, males aged 9 months.Results. The total length of the vessels in the area of the dentate gyrus is 2.5 times greater in transgenic animal models of Alzheimer’s disease than in animals of the control group (p < 0.01). The average diameter of blood vessels in all areas of the hippocampus is smaller compared with the control (p < 0.05). Transgenic modeling of neurodegeneration in the CA2 zone of the hippocampus increases the relative area of tissue with increased permeability of blood-brain barrier (BBB) (17.80 [9.15; 36.75]) compared to control (1.38 [0.04; 7.60]) at p < 0.05. A similar difference (p < 0.05) is also observed in the hippocampal area CA1. A tendency (p > 0.05) to decrease the number of CD31+ endothelial cells in the dentate gyrus of the hippocampus (21.52 [17.56; 24.50]) in animals of the experimental group compared with the control group (23.08[21.18; 29.84]) was detected. A similar situation is observed in the CA2 and CA3 areas of the hippocampus.Conclusion. Neurodegenerative changes in the hippocampus of animals with a transgenic AD model are associated with impaired microcirculation in the brain tissue as a result of a reduction in the diameter and branching of blood vessels, and damage and increased permeability of BBB.Цель – изучение молекулярных механизмов нарушения структурно-функциональной целостности гематоэнцефалического барьера (ГЭБ) при хронической нейродегенерации  альцгеймеровского типа, ассоциированной с развитием церебральной ангипопатии. Материалы и методы. Опытная группа – генетическая модель болезни Альцгеймера (БА) – мыши линии B6SLJ -Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas, самцы в возрасте 9 мес. Контрольная группа – мыши линии C57BL/6 x SJL, самцы в возрасте 9 мес.Результаты. У животных с генетической моделью БА в зубчатой извилине гиппокампа  общая длина сосудов в 2,5 раза больше, чем у контрольной группы (p < 0,01), при этом  средний диаметр сосудов во всех областях гиппокампа меньше по сравнению с контролем (p < 0,05). Выявлено, что при генетическом моделировании  нейродегенерации в СА2 зоне гиппокампа наблюдается увеличение относительной  площади ткани с повышенной проницаемостью ГЭБ (17,80 [9,15;36,75]) по сравнению с контролем (1,38 [0,04;7,60]) при p < 0,05. Подобное различие (p < 0,05) наблюдается и в зоне СА1 гиппокампа. У животных опытной группы выявлена тенденция (p > 0,05) к снижению количества CD31+ эндотелиальных клеток в зубчатой извилине гиппокампа (21,52 [17,56; 24,50]) по сравнению с контролем (23,08 [21,18; 29,84]). Аналогичная ситуация наблюдается в зонах СА2 и СА3 гиппокампа.Заключение. Нейродегенеративные изменения в гиппокампе животных с генетической  моделью БА ассоциированы с нарушением микроциркуляции в ткани головного мозга в  результате сокращения диаметра и разветвленности сосудов, повреждения и повышения проницаемости ГЭБ

Differential Roles of Environmental Enrichment in Alzheimer’s Type of Neurodegeneration and Physiological Aging

Impairment of hippocampal adult neurogenesis in aging or degenerating brain is a well-known phenomenon caused by the shortage of brain stem cell pool, alterations in the local microenvironment within the neurogenic niches, or deregulation of stem cell development. Environmental enrichment (EE) has been proposed as a potent tool to restore brain functions, to prevent aging-associated neurodegeneration, and to cure neuronal deficits seen in neurodevelopmental and neurodegenerative disorders. Here, we report our data on the effects of environmental enrichment on hippocampal neurogenesis in vivo and neurosphere-forming capacity of hippocampal stem/progenitor cells in vitro. Two models – Alzheimer’s type of neurodegeneration and physiological brain aging – were chosen for the comparative analysis of EE effects. We found that environmental enrichment greatly affects the expression of markers specific for stem cells, progenitor cells and differentiated neurons (Pax6, Ngn2, NeuroD1, NeuN) in the hippocampus of young adult rats or rats with Alzheimer’s disease (AD) model but less efficiently in aged animals. Application of time-lag mathematical model for the analysis of impedance traces obtained in real-time monitoring of cell proliferation in vitro revealed that EE could restore neurosphere-forming capacity of hippocampal stem/progenitor cells more efficiently in young adult animals (fourfold greater in the control group comparing to the AD model group) but not in the aged rats (no positive effect of environmental enrichment at all). In accordance with the results obtained in vivo, EE was almost ineffective in the recovery of hippocampal neurogenic reserve in vitro in aged, but not in amyloid-treated or young adult, rats. Therefore, EE-based neuroprotective strategies effective in Aβ-affected brain could not be directly extrapolated to aged brain

Влияние инсулинорезистентности на нарушение метаболизма глюкозы в миндалине головного мозга при экспериментальной болезни Альцгеймера

Purpose. Glucose metabolism is tightly regulated in the brain. Aberrant glucose metabolism is an important feature of neurodegenerative diseases, as inAlzheimer’s disease. The transport of glucose to the cell membrane is realized through the activity of insulin-regulated aminopeptidase (IRAP) which controls transfer of glucose transporter to the plasma membrane. IRAP is considered as one of the key markers of insulin resistance in Alzheimer’s disease. However, the question of the mechanism of the action of the IRAP remains open. The aim of the study was to study the effect of IRAP expression on cells of the neuronal and glial lineage, glucose transporter (GLUT4) expression in the brain amygdala on emotional memory in animals with experimental Alzheimer’s disease.Materials and methods. The study was performed with two experimental models of Alzheimer’s disease in mice. The experimental group was mice of the CD1 line, males aged 4 months (Alzheimer’s disease model with the intra-hippocampal administration of beta-amyloid 1-42 (1 µl) bilaterally in the CA1 area). The control group was mice of the CD1 line, males aged 4 months (sham-operated animals with the intrahippocampal administration of Phosphate buffered salin (1 µl) bilaterally in the CA1). The genetic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon, PSEN1*M146L*L286V) 6799Vas, males aged 4 months. The control group consisted of C57BL/6xSJL mice, males aged 4 months. Evaluation of emotional memory was carried out using “Fear conditioning” protocol. Expression of molecule-markers of insulin-resistance in the amygdala was studied by immunohistochemistry followed by confocal microscopy.Results. Aberrant associative learning and emotional memory was revealed in animals with an experimental model of Alzheimer’s disease. A decrease (p ≤ 0,05) of IRAP expression on cells of neuronal and glial nature, associated with GLUT4 down-regulation was detected in amygdala of brain in animals with experimental Alzheimer’s disease.Conclusion. Decreased number of IRAP-immunopositive neuronal and astroglial cells, as well as IRAP+/ GLUT4+ in cells of amygdala in animals with an experimental model of Alzheimer’s disease, indicates the development of insulin resistance in amygdala of brain, which was in correlation with the hippocampus in performing cognitive functions and memorizing associated with emotionally colored events. Цель. В головном мозге метаболизм глюкозы четко регулируется, поэтому его нарушение является важной особенностью нейродегенеративных заболеваний, в частности болезни Альцгеймера. Транспорт глюкозы в мембрану клетки реализуется за счет активности инсулин-регулируемой аминопептидазы (IRAP), которая влияет на память и обучение, и рассматривается как один из ключевых маркеров инсулинорезистентности при болезни Альцгеймера. Однако вопрос о механизме действия IRAP остается открытым. Цель исследования – изучение влияния экспрессии IRAP на клетках нейрональной и глиальной природы, а также совместно с инсулинзависимым глюкозным транспортером (GLUT4) в миндалине головного мозга на эмоциональную память у животных с экспериментальной болезнью Альцгеймера.Материал и методы. Исследование проводили на животных с использованием двух экспериментальных моделей болезни Альцгеймера – инъекционной и генетической. Опытная группа – мыши линии CD1, самцы в возрасте 4 мес, которым билатерально вводили бета-амилоид 1-42 в зону гиппокампа CA1 (сornu аmmonis)по 1 мкл. Контрольная группа – мыши линии CD1, самцы в возрасте 4 мес, которым билатерально вводили растворитель для бета-амилоида – фосфатно-солевой буфер в зону CA1 по 1 мкл.Генетическая модель болезни Альцгеймера – мыши линии B6SLJ –Tg(APPSwFlLon,PSEN1*M146L*L286 V)6799Vas, самцы в возрасте 4 мес. Контрольная группа – мыши линии C57BL/6xSJL, самцы в возрасте 4 мес. Оценку эмоциональной памяти проводили с использованием нейроповеденческого тестирования Fear conditioning. Экспрессию молекул-маркеров инсулинорезистентности в миндалине изучали методом иммуногистохимии с последующей конфокальной микроскопией.Результаты. У животных с экспериментальной моделью болезни Альцгеймера выявлено нарушение ассоциативного обучения и эмоциональной памяти. Выявлено снижение (р ≤ 0,05) экспрессии IRAP на клетках нейрональной и глиальной природы, а также (совместно с GLUT4) в миндалине головного мозга у животных с экспериментальной болезнью Альцгеймера.Заключение. Уменьшение числа IRAP-иммунопозитивных нейрональных и астроглиальных клеток, а также экспрессии IRAP/GLUT4 в клетках миндалины у животных с экспериментальной моделью болезни Альцгеймера указывает на развитие инсулинорезистентности в миндалине головного мозга, находящейся во взаимосвязи с гиппокампом при осуществлении когнитивных функций и запоминания, сопряженных с эмоционально окрашенными событиями.

Заболеваемость злокачественными новообразованиями кожи в Красноярском крае

Skin cancer is one of the most common malignancies and its increasing rates are found all over the world and in the Russian Federation in particular. The paper presents statistical analysis of the data on skin cancer morbidity and mortality rates in Krasnoyarsk Region summarized for the period since 1999 until 2005. Peculiarities of occurrence of this pathology among male and female persons are evaluated, tendencies of epidemiology of these tumors are analyzed, and comparative analysis of skin cancer morbidity in Krasnoyarsk Region with the Russian Federation as a whole and with foreign countries is carried out.Злокачественные новообразования кожи являются одной из наиболее частых онкологических патологий. В последние десятилетия регистрируется неуклонный рост поражения человека данным видом опухолей во всем мире, в том числе на территории Российской Федерации. В представленной работе проведен статистический анализ заболеваемости злокачественными новообразованиями кожи в Красноярском крае, исследована ее динамика с 1999 по 2005 г., оценены особенности возникновения патологии среди лиц мужского и женского пола, проанализированы тенденции эпидемиологии данного вида опухолей, проведен сравнительный анализ заболеваемости раком кожи со статистическими показателями Российской Федерации, зарубежных стран

Adipocytokines and CD34+ Progenitor Cells in Alzheimer's Disease

BACKGROUND: Alzheimer's disease (AD) and atherosclerosis share common vascular risk factors such as arterial hypertension and hypercholesterolemia. Adipocytokines and CD34(+) progenitor cells are associated with the progression and prognosis of atherosclerotic diseases. Their role in AD is not adequately elucidated. METHODS AND FINDINGS: In the present study, we measured in 41 patients with early AD and 37 age- and weight-matched healthy controls blood concentrations of adiponectin and leptin by enzyme linked immunoabsorbent assay and of CD34(+) progenitor cells using flow cytometry. We found significantly lower plasma levels of leptin in AD patients compared with the controls, whereas plasma levels of adiponectin did not show any significant differences (AD vs. control (mean ± SD): leptin:8.9 ± 5.6 ng/mL vs.16.3 ± 15.5 ng/mL;P = 0.038; adiponectin:18.5 ± 18.1 µg/mL vs.16.7 ± 8.9 µg/mL;P = 0.641). In contrast, circulating CD34(+) cells were significantly upregulated in AD patients (mean absolute cell count ± SD:253 ± 51 vs. 203 ± 37; P = 0.02) and showed an inverse correlation with plasma levels of leptin (r =  -0.248; P = 0.037). In logistic regression analysis, decreased leptin concentration (P = 0.021) and increased number of CD34(+) cells (P = 0.036) were both significantly associated with the presence of AD. According to multifactorial analysis of covariance, leptin serum levels were a significant independent predictor for the number of CD34(+) cells (P = 0.002). CONCLUSIONS: Our findings suggest that low plasma levels of leptin and increased numbers of CD34(+) progenitor cells are both associated with AD. In addition, the results of our study provide first evidence that increased leptin plasma levels are associated with a reduced number of CD34(+) progenitor cells in AD patients. These findings point towards a combined involvement of leptin and CD34(+) progenitor cells in the pathogenesis of AD. Thus, plasma levels of leptin and circulating CD34(+) progenitor cells could represent an important molecular link between atherosclerotic diseases and AD. Further studies should clarify the pathophysiological role of both adipocytokines and progenitor cells in AD and possible diagnostic and therapeutic applications

Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy

<p>Abstract</p> <p>Background</p> <p>Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- and taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In this work we questioned whether the synthetic steroid mifepristone, which as monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing repopulation of ovarian cancer cells if given after a round of lethal cisplatin-paclitaxel combination treatment.</p> <p>Methods</p> <p>We established an <it>in vitro</it> approach wherein ovarian cancer cells with various sensitivities to cisplatin or paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus paclitaxel for 3 h. Thereafter, cells were maintained in media with or without mifepristone, and short- and long-term cytotoxicity was assessed.</p> <p>Results</p> <p>Four days after treatment the lethality of cisplatin-paclitaxel was evidenced by reduced number of cells, increased hypodiploid DNA content, morphological features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its downstream substrate PARP. Short-term presence of mifepristone either enhanced or did not modify such acute lethality. Seven days after receiving cisplatin-paclitaxel, cultures showed signs of relapse with escaping colonies that repopulated the plate in a time-dependent manner. Conversely, cultures exposed to cisplatin-paclitaxel followed by mifepristone not only did not display signs of repopulation following initial chemotherapy, but they also had their clonogenic capacity drastically reduced when compared to cells repopulating after cisplatin-paclitaxel.</p> <p>Conclusions</p> <p>Cytostatic concentrations of mifepristone after exposure to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of remnant cells surviving and escaping the cytotoxic drugs.</p