Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

BACKGROUND: We are investigating a double transgenic rat (dTGR) model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1) are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression. Furthermore we show evidence that Ang II causes the upregulation of NF-{kappa}B in our model. METHODS: We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc) and age-matched SD rats. Blood-pressure- and albuminuria- measurements were monitored during the treatment period (four weeks). The seven weeks old animals were killed, hearts and kidneys were isolated and used for immunohistochemical-and electromobility shift assay analysis. RESULTS: Chronic treatment with the antioxidant PDTC decreased blood pressure (162 plus minus 8 vs. 190 plus minus 7 mm Hg, p = 0.02). Cardiac hypertrophy index was significantly reduced (4.90 plus minus 0.1 vs. 5.77 plus minus 0.1 mg/g, p < 0.001) compared to dTGR. PDTC reduced 24 h albuminuria by 85 % (2.7 plus minus 0.5 vs. 18.0 plus minus 3.4 mg/d, p < 0.001) and prevented death significantly. Vascular injury was ameliorated in small renal and cardiac vessels. PDTC inhibited NF-{kappa}B binding activity in heart and kidney. Immunohistochemical analysis shows increased expression of the p65 NF-{kappa}B subunit in the endothelium, smooth muscles cells of damaged small vessels, infiltrated cells, glomeruli, tubuli and collecting ducts of dTGR. PDTC markedly reduced the immunoreactivity of p65. CONCLUSION: Our data show that inhibition of NF-{kappa}B by PDTC markedly reduces inflammation, iNOS expression in the dTGR most likely leading to decreased cytotoxicity, and cell proliferation. Thus, NF-{kappa}B activation plays an important role in ANG II-induced end-organ damage

Проектирование автоматизированной системы управления блочно-кустовой насосной станции

Данная работа является проектом разработки автоматизированной компьютерной системы управления. Представлен выбор технических и программных средств, математический аппарат и программное обеспечение при проектирование автоматизированных систем управления SCADA. В работе отражены физические основы работы устройств АС, протоколов и интерфейсов систем автоматизации технологических процессов, требования ГОСТ по разработке технической документации проектов АС.This work is a project for the development of an automated computer control system. The choice of hardware and software, mathematical apparatus and software for the design of automated control systems SCADA. The work reflects the physical basis of the AC devices, protocols and interfaces of process automation systems, the requirements of GOST for the development of technical documentation of AC projects

Технологические решения для строительства разведочной вертикальной скважины глубиной 2650 метров на нефтяном месторождении (Тюменская область)

Объектом исследования является разведочная вертикальная скважина глубиной 2650 метров на нефтяном месторождении (Тюменская область). Целью работы является – спроектировать технологическое решения для бурения вертикальной разведочной скважины, геолого-технический наряд, компоновки низа бурильной колонны, интервалы бурении и спуск обсадных колонн, интервалы цементирования.The object of the study is a vertical exploratory well with a depth of 2,650 meters in an oil field (Tyumen Oblast). The aim of the work is to design technological solutions for drilling a vertical exploration well, geological and technical outfit, layouts of the bottom of the drill string, drilling intervals and running of the casing strings, cementing intervals

Why are mineralocorticoid receptor antagonists cardioprotective?

Two clinical trials, the Randomized ALdosterone Evaluation Study (RALES) and the EPlerenone HEart failure and SUrvival Study (EPHESUS), have recently shown that mineralocorticoid receptor (MR) antagonists reduce mortality in patients with heart failure on top of ACE inhibition. This effect could not be attributed solely to blockade of the renal MR-mediated effects on blood pressure, and it has therefore been proposed that aldosterone, the endogenous MR agonist, also acts extrarenally, in particular in the heart. Indeed, MR are present in cardiac tissue, and possibly aldosterone synthesis occurs in the heart. This review critically addresses the following questions: (1) is aldosterone synthesized at cardiac tissue sites, (2) what agonist stimulates cardiac MR normally, and (3) what effects are mediated by aldosterone/MR in the heart that could explain the beneficial effects of MR blockade in heart failure? Conclusions are that most, if not all, of cardiac aldosterone originates in the circulation (i.e., is of adrenal origin), and that glucocorticoids, in addition to aldosterone, may serve as the endogenous agonist of cardiac MR. MR-mediated effects in the heart include effects on endothelial function, cardiac fibrosis and hypertrophy, oxidative stress, cardiac inotropy, coronary flow, and arrhythmias. Some of these effects occur via or in synergy with angiotensin II, and involve a non-MR-mediated mechanism. This raises the possibility that aldosterone synthase inhibitors might exert beneficial effects on top of MR blockade

The mineralocorticoid receptor and oxidative stress

Reactive oxygen species are profoundly important for many physiologic functions and are also pivotal to numerous disease processes, particularly those involving inflammation. Much evidence has accrued demonstrating that aldosterone acts locally in many cells aside from those in the cortical collecting duct. Peripheral blood monocytes and vascular smooth muscle cells are both influenced by aldosterone to produce reactive oxygen species. This production contributes to nuclear factor kappaB (NF-kappaB) activation and the genes regulated by this transcription factor. Aldosterone thereby plays an important role in atherosclerosis and hypertension-induced vascular injury. Aldosterone interacts with angiotensin (Ang) II-induced signaling. Both aldosterone and Ang II initiate ERK1/2 and JNK signaling; the effects of the two compounds is additive and involves the epidermal growth factor receptor. Recent data suggest that reactive oxygen species, might contribute to aldosterone production in nonadrenal tissues. A novel oxidized derivative of linoleic acid is a prime candidate in this regard. Oxidative stress may impair mineralocorticoid receptor function by inhibiting aldosterone binding. The latter finding has particularly important implications for elderly persons who exhibit increased oxidative stress and who are at risk for diminished aldosterone function in the distal nephron and subsequent hyperkalemia

За кадры. 1932. № 5

К годовщине ударного института еще усилии борьбу за Красное Знамя- классовую борьбу за качество и тонны в учебе. К 1-му мая лучшие показателиК 1-му мая выполнить данные обещания во время обмена комсомольских билетов. Комсомол на передовые позиции борьбы за качество учебы / ТитовСоревнование научных работников - на высшую ступень / Н. ФурманМассовый первомайский рейд ознаменуем: скорейшим проведением в жизнь решений Горкома партии о ВТУЗах, новым притоком студентов и преподавателей в ударники, лучших ударников в партию, беспощадной борьбой с оппортунизмом и неповоротливостью. В ударный поход за качество учебыКоммунист в передовые борцы социалистических форм труда / И. ФурманЗадачи маршрутовСводка электроспециальности5-ая группа в подготовке к 1-му мая / БагаевРаботе добровольных обществ - большевистские темпы / ТурчинЗа культурное общежитие / КалннчевВнимание организации общества помощи Борцам Революции / КопьевОбеспечить перестройку работы ОСО, поднять его роль в деле обеспечения безусловной и в нужный момент несокрушимой защиты ССиР / Мостово