4 research outputs found
Long-term planning and its role as a tool of fiscal security of the economy
Актуальность исследования определяется тем, что обеспечение бюджетно-финансовой безопасности в России связано с проведением исполнительными органами государственной власти бюджетно-финансового планирования, основанного на принципах законности, плановости и открытости, прописанных в Бюджетном кодексе РФ. Все это рождает острую необходимость принятия базового документа (Долгосрочной бюджетной стратегии). Цель работы: провести анализ бюджетно-финансового планирования в его историческом, межстрановом и правовом аспектах, дать характеристику современного состояния бюджетно-финансового планирования в России. Методы исследования: моделирование, обобщение зарубежного опыта использования долгосрочного планирования, сопоставление и контент-анализ, который позволил выявить принципы долгосрочного планирования в бюджетной сфере, а также острую необходимость принятия Долгосрочной бюджетной стратегии на современном этапе в России. Результаты. Проведенное исследование отражает генезис бюджетного планирования в России в 1917-2017 гг. Анализ применения такого планирования в развитых странах (США, Германия, Великобритания, Франция и др.) определил основные принципы, которые могут быть заложены в основу Долгосрочной бюджетной стратегии в России на федеральном и региональном уровнях. Как основной базовый документ бюджетно-финансового планирования текущего периода утвержденная Долгосрочная бюджетная стратегия позволит предопределить результаты долгосрочного развития и обеспечить достаточный уровень экономической безопасности бюджетно- финансовой сферы.The relevance of this research is determined by the fact that ensuring fiscal security in Russia is connected with the Executive bodies of state power, budget and financial planning based on the principles of legality, planning and openness spelled out in the Budget code of the Russian Federation. All this creates an urgent need of adoption of the core document (Long-term budget strategy). The aim of the work is to analyze the budget and financial planning in its historical, interstate and legal aspects, State of fiscal planning in Russia. Research methods: modeling, generalization of foreign experience in using long-term planning. Comparison and content analysis, which allowed revealing the principles of long-term planning in the budgetary sphere and urgent need to adopt a Long-term budget strategy at the present stage in Russia. Results. The study reflects the Genesis of budget planning in Russia in 1917-2017. Analysis of application of such planning in developed countries (USA, Germany, UK, France, etc.) helped identify basic principles that can be the base of Long-term budget strategy in Russia at Federal and regional levels. The approved Long-term budget strategy, as the base document for budget and financial planning of the current period, will enable to predetermine the outcome of long-term development and to ensure a sufficient level of economic security fiscal sphere
Nitric oxide stress in sporadic inclusion body myositis muscle fibres: inhibition of inducible nitric oxide synthase prevents interleukin-1 beta-induced accumulation of beta-amyloid and cell death
Sporadic inclusion body myositis is a severely disabling myopathy. The
design of effective treatment strategies is hampered by insufficient
understanding of the complex disease pathology. Particularly, the nature
of interrelationships between inflammatory and degenerative
pathomechanisms in sporadic inclusion body myositis has remained
elusive. In Alzheimer’s dementia, accumulation of beta-amyloid has been
shown to be associated with upregulation of nitric oxide. Using
quantitative polymerase chain reaction, an overexpression of inducible
nitric oxide synthase was observed in five out of ten patients with
sporadic inclusion body myositis, two of eleven with dermatomyositis,
three of eight with polymyositis, two of nine with muscular dystrophy
and two of ten non-myopathic controls. Immunohistochemistry confirmed
protein expression of inducible nitric oxide synthase and demonstrated
intracellular nitration of tyrosine, an indicator for intra-fibre
production of nitric oxide, in sporadic inclusion body myositis muscle
samples, but much less in dermatomyositis or polymyositis, hardly in
dystrophic muscle and not in non-myopathic controls. Using fluorescent
double-labelling immunohistochemistry, a significant co-localization was
observed in sporadic inclusion body myositis muscle between
beta-amyloid, thioflavine-S and nitrotyrosine. In primary cultures of
human myotubes and in myoblasts, exposure to interleukin-1 beta in
combination with interferon-gamma induced a robust upregulation of
inducible nitric oxide synthase messenger RNA. Using fluorescent
detectors of reactive oxygen species and nitric oxide,
dichlorofluorescein and diaminofluorescein, respectively, flow cytometry
revealed that interleukin-1 beta combined with interferon-gamma induced
intracellular production of nitric oxide, which was associated with
necrotic cell death in muscle cells. Intracellular nitration of tyrosine
was noted, which partly co-localized with amyloid precursor protein, but
not with desmin. Pharmacological inhibition of inducible nitric oxide
synthase by 1400W reduced intracellular production of nitric oxide and
prevented accumulation of beta-amyloid, nitration of tyrosine as well as
cell death inflicted by interleukin-1 beta combined with
interferon-gamma. Collectively, these data suggest that, in skeletal
muscle, inducible nitric oxide synthase is a central component of
interactions between interleukin-1 beta and beta-amyloid, two of the
most relevant molecules in sporadic inclusion body myositis. The data
further our understanding of the pathology of sporadic inclusion body
myositis and may point to novel treatment strategies
Acid Sphingomyelinase Is Required for Protection of Effector Memory T Cells against Glucocorticoid-Induced Cell Death
The activity of acid sphingomyelinase (aSMase) was previously reported to be involved in glucocorticoid-induced cell death (GICD) of T lymphocytes. This mechanism in turn is believed to contribute to the therapeutic efficacy of glucocorticoids (GCs) in the treatment of inflammatory diseases. In this study, we reassessed the role of aSMase in GICD by using aSMase knockout mice. The absence of aSMase largely abolished the partial protection that effector memory CD4(+) T cells in wild-type mice possess against GICD. Reduced IL-2 secretion by aSMase-deficient CD4(+) T cells suggested that a lack of this important survival factor might be the cause of these cells' enhanced susceptibility to GICD. Indeed, addition of IL-2 restored the protection against GICD, whereas neutralization of IL-2 abrogated the otherwise protective effect seen in wild-type effector memory CD4(+) T cells. The therapeutic implications of the altered sensitivity of aSMase-deficient T cells to GICD were assessed in models of inflammatory disorders; namely, experimental autoimmune encephalomyelitis and acute graft-versus-host disease. Surprisingly, GC treatment was equally efficient in both models in terms of ameliorating the diseases, regardless of the genotype of the T cells. Thus, our data reveal a hitherto unrecognized contribution of aSMase to the sensitivity of effector memory CD4(+) T cells to GICD and call into question the traditionally attributed importance of GICD of T cells to the treatment of inflammatory diseases by GCs. The Journal of Immunology, 2011, 187: 4509-4516
Airway epithelial cells are crucial targets of glucocorticoids in a mouse model of allergic asthma
Although glucocorticoids (GCs) are a mainstay in the clinical management of asthma, the target cells that mediate their therapeutic effects are unknown. Contrary to our expectation, we found that GC receptor (GR) expression in immune cells was dispensable for successful therapy of allergic airway inflammation (AAI) with dexamethasone. Instead, GC treatment was compromised in mice expressing a defective GR in the nonhematopoietic compartment or selectively lacking the GR in airway epithelial cells. Further, we found that an intact GR dimerization interface was a prerequisite for the suppression of AAI and airway hyperresponsiveness by GCs. Our observation that the ability of dexamethasone to modulate gene expression in airway epithelial cells coincided with its potency to resolve AAI supports a crucial role for transcriptional regulation by the GR in this cell type. Taken together, we identified an unknown mode of GC action in the treatment of allergic asthma that might help to develop more specific therapies in the future