THE ROLE AND SIGNIFICANCE OF STATE IN THE DEVELOPMENT OF THE ECONOMY

The article is dedicated to state financial control in the Uzbekistan. In work legal bases in functioning structures of the state financial control, the principles activity of financial control structure are considered; directions of perfection in the state financial control are offered

Influence of macrophages on the insulin-synthesizing system under normal conditions and in alloxan diabetes

Insulin-synthesizing cells (ISCs) of pancreatic gland are localized both in its islets, and in exocrine portion, as single cells or cellular agglomerates. ISCs differ in their morphological and functional characteristics, depending on characteristics of the microenvironment. Resident macrophages are also involved into formation of their microenvironment. Our purpose was to assess the effect of functional macrophages upon the insulinsynthesizing system (pancreatic islets, cell agglomerates, and separately lying insulin-synthesizing cells) under normal conditions and in alloxan diabetes.Alloxan diabetes was induced in mature male Wistar rats by intraperitoneal injection of alloxan (30 mg/100 g). Functional activity of macrophages was modeled with anti-inflammatory drug aminophthalhydrazide (AMP). Contents of insulin, glucose, and glycosylated hemoglobin were measured in blood of experimental animals. The levels of IL-1α, TNFα and IFNγ were determined in pancreatic homogenate. The number of macrophages was counted in histological preparations from the insular and exocrine parts of the organ, as well as the number of pancreatic islets, agglomerates, and single ISCs. The amounts of proliferating cells (insulin+Ki-67+), apoptotic forms (TUNEL+insulin+), and insulin content of ISCs at different sites (according to their fluorescence intensity) were determined. All pancreatic islets were divided into 3 types, according to intensity of insulin fluorescence, i.e., islets with high, median and low levels of fluorescence.In healthy rats, immunomodulation reduced total level of IL-1α in pancreatic parenchyma, without changing the overall parameters of carbohydrate metabolism. In the exocrine part of pancreas, the content of single ISCs in ductal epithelium was increased. Likewise, proliferation of the ISC agglomerates became higher. The intensity of β-cell apoptosis increased in pancreatic islets. The proportion of islets with high-level insulin fluorescence was decreased, along with lower density of macrophages and proliferation rates of β-cells, and higher apoptosis rates, than in intact animals. We have also revealed there an increased ratio of cells with average insulin levels. In the islets with low insulin content, immunomodulation did not cause morphological changes. Administration of AMP in alloxan diabetes contributes to a significantly decreased concentration of IFNγ in pancreatic tissues, stabilizes IL-1α content, along with reduced apoptosis of ISCs and macrophage infiltration in all parts of the gland. In the ductal epithelium, a large number of single ISCs with high synthetic activity was observed, with retained number of agglomerates and their increased cellularity. The number of dividing β-cells is increased in pancreatic islets.Modulation of the functional activity of pancreatic macrophages under physiological conditions provides a multidirectional effect on the insulin-synthesizing cells, depending on their localization. In exocrine part of the organ, where M2 macrophages are located, we have observed activated differentiation and proliferation of ISC precursors. Meanwhile, in the islets where M1 macrophages are present, apoptosis of β-cells was enhanced. In alloxan diabetes, immunomodulation was associated with reduced destruction of insulinocytes, along with high intensity of their proliferation. Heterogenous response of ISCs to the changes in the microenvironment depends on their synthetic activity. In healthy rats, the islets with high level of insulin fluorescence, the level of apoptosis is increased, and β-cell proliferation is reduced, while the morphological and functional characteristics of islets with low-level insulin fluorescence did not change. In alloxan diabetes, apoptosis prevailed in islets with high fluorescence values, whereas β-cell proliferation predominated in the islets with low insulin contents

Capacity of second spillway of Boguchanskaya HPP

The main problem in designing the discharge of water flow from the upstream to the downstream is to ensure the capacity of spillway structures. This article discusses the design options for the design top of the spillway: with water diversion through a short nozzle in the pressure mode and energy dissipation in stilling basin, with the pressure-free and pressure-free passage of water through spillway No. 2 and damping of the flow energy by jet discharge into the lower stream by the inclined face of the threshold in the stilling basin; with no pressure passage and pressure passage of water through spillway No 2 and energy dissipation of the flow by throwing the flow discharge into the downstream by the inclined face of the threshold of a stilling basin; with the passage of building expenses through the sill in no pressure and pressure-type short-nozzle modes, with the spillway No. 2’s horizontal water outlet at the level of 139.5 m, with a jet discharge by a toe-springboard at an angle of 35°, and with the outlet rib's mark of 143.8 m. This article aims to obtain the flow characteristics of the considered spillway option for the period of temporary operation of the hydrotechnical complex

Sinusoidal cells and cytokine response in the tetrachloromethane-induced hepatotoxicity and an approach to its correction

High occurence of liver diseases (toxic, viral hepatitis, liver failure, cirrhosis) requires urgent search of new methods for management of the hepatobiliary diseases. At the present time, the role of immune mechanisms in pathogenesis of diffuse toxic liver damage is not finally clarified. The model of toxic hepatitis induced by carbon tetrachloride (CCl4) is widely known, but this approach allows us to perform complex evaluation and develop the methods for adequate correction of liver disorders in experimental model, which is not always feasible in clinical setting. To design a model of diffuse toxic liver damage, the CCl4 oil solution was used, having been administered intraperitoneally to experimental animals, at a single dose of 50 mg per 100 g body mass. Aiming for correction of toxic liver damage, the injections of aminophthalhydrazide (APH) to experimental animals were carried out intramuscularly at the dose of 2 mg/kg over the terms of experiment. An evaluation of the role of sinusoidal cells (SC) and cytokine production at the local and systemic level were carried out in the model of toxic liver damage caused by CCl4 and its correction by APH treatment. In the course of developing diffuse toxic liver damage induced by CCl4, the production of proinflammatory cytokines TNFα, IL-1α and IL-18 was enhanced at the local level, whereas an increase in TNFα concentration was observed in blood plasma. Following aminophthalhydrazide (APH) administration, the concentrations of proinflammatory cytokines (TNFα and IL-18) decreased at system level, along with locally decreased levels of IL-6 and IFNγ. Changes in the functional state of immunocompetent cells, which include sinusoidal cells (SC), have a significant impact on the development of pathological processes in the liver. The results of our study presume that, over the early periods of toxic impact upon liver tissue, the number of SCs increases both due to influx of blood monocytes and mature macrophages from the peritoneal cavity that enter the injury site directly via mesothelial layer. The SCs provide phagocytosis of damaged hepatocytes and contribute to resolution of the inflammatory process. Modulation of the macrophage activities by APH contributes to increased amounts of SCs at the early stages, and stabilizes their quantities after 2 weeks of APH injections. Change in the numbers of liver SCs during toxic damage affects the production of cytokines. A direct effect of APH upon the SCs may change the production of regulatory factors and compensate the insufficient rate of recovery processes after the toxic damage. © 2019, SPb RAACI

Feasibility and safety of high-dose adenosine perfusion cardiovascular magnetic resonance

<p>Abstract</p> <p>Introduction</p> <p>Adenosine is the most widely used vasodilator stress agent for Cardiovascular Magnetic Resonance (CMR) perfusion studies. With the standard dose of 140 mcg/kg/min some patients fail to demonstrate characteristic haemodynamic changes: a significant increase in heart rate (HR) and mild decrease in systolic blood pressure (SBP). Whether an increase in the rate of adenosine infusion would improve peripheral and, likely, coronary vasodilatation in those patients is unknown. The aim of the present study was to assess the tolerance and safety of a high-dose adenosine protocol in patients with inadequate haemodynamic response to the standard adenosine protocol when undergoing CMR perfusion imaging.</p> <p>Methods</p> <p>98 consecutive patients with known or suspected coronary artery disease (CAD) underwent CMR perfusion imaging at 1.5 Tesla. Subjects were screened for contraindications to adenosine, and an electrocardiogram was performed prior to the scan. All patients initially received the standard adenosine protocol (140 mcg/kg/min for at least 3 minutes). If the haemodynamic response was inadequate (HR increase < 10 bpm or SBP decrease < 10 mmHg) then the infusion rate was increased up to a maximum of 210 mcg/kg/min (maximal infusion duration 7 minutes).</p> <p>Results</p> <p>All patients successfully completed the CMR scan. Of a total of 98 patients, 18 (18%) did not demonstrate evidence of a significant increase in HR or decrease in SBP under the standard adenosine infusion rate. Following the increase in the rate of infusion, 16 out of those 18 patients showed an adequate haemodynamic response. One patient of the standard infusion group and two patients of the high-dose group developed transient advanced AV block. Significantly more patients complained of chest pain in the high-dose group (61% vs. 29%, p = 0.009). On multivariate analysis, age > 65 years and ejection fraction < 57% were the only independent predictors of blunted haemodynamic responsiveness to adenosine.</p> <p>Conclusions</p> <p>A substantial number of patients do not show adequate peripheral haemodynamic response to standard-dose adenosine stress during perfusion CMR imaging. Age and reduced ejection fraction are predictors of inadequate response to standard dose adenosine. A high-dose adenosine protocol (up to 210 mcg/kg/min) is well tolerated and results in adequate haemodynamic response in nearly all patients.</p

Prognostic utility of sestamibi lung uptake does not require adjustment for stress-related variables: A retrospective cohort study

BACKGROUND: Increased (99m)Tc-sestamibi stress lung-to-heart ratio (sLHR) has been shown to predict cardiac outcomes similar to pulmonary uptake of thallium. Peak heart rate and use of pharmacologic stress affect the interpretation of lung thallium uptake. The current study was performed to determine whether (99m)Tc-sestamibi sLHR measurements are affected by stress-related variables, and whether this in turn affects prognostic utility. METHODS: sLHR was determined in 718 patients undergoing (99m)Tc-sestamibi SPECT stress imaging. sLHR was assessed in relation to demographics, hemodynamic variables and outcomes (mean follow up 5.6 ± 1.1 years). RESULTS: Mean sLHR was slightly greater in males than in females (P < 0.01) and also showed a weak negative correlation with age (P < 0.01) and systolic blood pressure (P < 0.01), but was unrelated to stress method or heart rate at the time of injection. In patients undergoing treadmill exercise, sLHR was also positively correlated with peak workload (P < 0.05) but inversely with double product (P < 0.05). The combined explanatory effect of sex, age and hemodynamic variables on sLHR was less than 10%. The risk of acute myocardial infarction (AMI) or death increased by a factor of 1.7–1.8 for each SD increase in unadjusted sLHR, and was unaffected by adjustment for sex, age and hemodynamic variables (hazard ratios 1.6–1.7). The area under the ROC curve for the unadjusted sLHR was 0.65 (95% CI 0.59–0.71, P < 0.0001) and was unchanged for the adjusted sLHR (0.65, 95% CI 0.61–0.72, P < 0.0001). CONCLUSION: Stress-related variables have only a weak effect on measured sLHR. Unadjusted and adjusted sLHR provide equivalent prognostic information for prediction of AMI or death

The modulling influence of macrophages on recovery of structural changes of vascular tunic of eye in experimental diabetes

We showed that macrophages regulate a character and degree ot inflammatory process in pigmented layer and vascular tunic of eye in diabetic retinitis. Meanwhile, the modulation of their functional activity by the preparation «Tamerite» have resulted in regeneration of quantity and their functioning of melanocyte of pigment tunic and stimulation of angiogenesis vascular tunic of eye.В результате экспериментального исследования было установлено, что в условиях диабетической ретинопатии макрофаги определяют характер и выраженность воспалительного процесса пигментной и сосудистой оболочки глаза. Модуляция их функциональной активности препаратом «Тамерит» способствовала восстановлению популяции и функционирования меланоцитов пигментного слоя, стимуляции ангиогенеза в сосудистой оболочке глаза и обратному развитию склеротических изменений

Macrophages role in the pathogenesis of toxic hepatitis in rats

In rats with acute toxic hepatitis caused by CL4 injection the macrophages modulating activity at early stages of the disease development lessens the inflammatory reaction manifestation, intensifies the recovery processes in the liver which are demonstrated by an increase in the number of binuclear hepatocytes and mitosis cells.У крыс с острым токсическим гепатитом, вызванным введением CL4 модулирование активности макрофагов на ранних этапах развития заболевания уменьшает выраженность воспалительной реакции, усиливает восстановительные процессы в печени, проявляющиеся в увеличении количества двуядерных и делящихся митозом гепатоцитов. При этом значительно снижается показатели эндогенной интоксикации и интенсивность свободнорадикального окисления

Protective Effects of a Rhodiola Crenulata Extract and Salidroside on Hippocampal Neurogenesis against Streptozotocin-Induced Neural Injury in the Rat

Previously we have demonstrated that a Rhodiola crenulata extract (RCE), containing a potent antioxidant salidroside, promotes neurogenesis in the hippocampus of depressive rats. The current study was designed to further investigate the protective effect of the RCE on neurogenesis in a rat model of Alzheimer's disease (AD) induced by an intracerebroventricular injection of streptozotocin (STZ), and to determine whether this neuroprotective effect is induced by the antioxidative activity of salidroside. Our results showed that pretreatment with the RCE significantly improved the impaired neurogenesis and simultaneously reduced the oxidative stress in the hippocampus of AD rats. In vitro studies revealed that (1) exposure of neural stem cells (NSCs) from the hippocampus to STZ strikingly increased intracellular reactive oxygen species (ROS) levels, induced cell death and perturbed cell proliferation and differentiation, (2) hydrogen peroxide induced similar cellular activities as STZ, (3) pre-incubation of STZ-treated NSCs with catalase, an antioxidant, suppressed all these cellular activities induced by STZ, and (4) likewise, pre-incubation of STZ-treated NSCs with salidroside, also an antioxidant, suppressed all these activities as catalase: reduction of ROS levels and NSC death with simultaneous increases in proliferation and differentiation. Our findings indicated that the RCE improved the impaired hippocampal neurogenesis in the rat model of AD through protecting NSCs by its main ingredient salidroside which scavenged intracellular ROS