Personalized management of hypertensive patients: focus on prognostic biomarkers

Aim. To analyze level of circulating biomarkers of plasma vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) during 3-month therapy with a fixed-dose combination of ramipril/indapamide (Konsilar-D24, AO Vertex, Russia), as well as to evaluate the antihypertensive efficacy of a fixed-dose combination of ramipril/indapamide (Konsilar-D24, JSC “Vertex”, Russia) in hypertensive (HTN) patients with type 2 diabetes (T2D).Material and methods. This prospective open-label study included 44 patients (aged 35 to 60 years) of both sexes with essential grade 1-2 HTN and concomitant compensated T2D, who did not reach the target blood pressure (BP) level using single or dual antihypertensive therapy, as well as patients who did not take antihypertensives. All patients included in the study initially underwent a set of standard clinical, laboratory and functional examinations in accordance with the clinical guidelines for the management of patients with HTN and T2D, as well as an assessment of the level of C-reactive protein, VEGF and TNF-α. Patients were monitored and treated with Konsilar-D24 for 3 months.Results. In 93,2% of patients, individual target BP values were achieved during the first 2-4 weeks of therapy with a fixed combination of ramipril/indapamide (Konsilar-D24). In the subsequent 3-month follow-up, the average daily BP level in all patients ranged from 129/79 mm Hg to 110/70 mm Hg. Three-month Konsilar-D24 therapy showed a decrease in microalbuminuria: the median values of microalbuminuria decreased by 2 times, and the decrease in the maximum recorded values reached 40% of the baseline. Decrease in mean TNF-α values after 3-month therapy with Konsilar-D24 was 33% of the baseline values, while the maximum recorded values during the specified period decreased by 17%. Decrease in median VEGF values after 3-month Konsilar-D24 therapy was 28%, while the maximum value decreased by 7%, the minimum — by 8%.Conclusion. Konsilar-D24 improves the prognosis in hypertensive patients not only by reducing BP to target values, but also by reducing the level of VEGF and TNF-α biomarkers that determine the progression of endothelial dysfunction, diabetic retinopathy, and microalbuminuria

Implementation of human rights in the context of COVID-19 pandemic

The subject of the article is the legal basis of human rights and freedoms, including their restriction as one of the aspects of the COVID-19 pandemic. The purpose of the research is to confirm or confute the hypothesis that the restriction of human rights in particular the right to life, the right to health and freedom of movement in Russia during COVID-19 pandemic is legally justified.The methodology of research includes the formal legal interpretation of legal acts as well as the comparative analysis of Russian and foreign legal literature. The authors analyze and interpret international law, including international treaties and the law of foreign states as well as law of the Russian Federation and the constituent entities of the Russian Federation.The main results. Restrictive measures of main human rights may lead to the violation of the constitutional rights and freedoms of citizens, and can also create conditions for abuse of authority while applying the rules governing the emergency situations. International human rights law allows the suspension of certain rights in an emergency that threatens the life of the nation. This can only be done in cases where the emergency has been officially declared, the adoption of emergency measures is caused by an urgent need in the current situation, does not contradict other obligations under international law, is limited in time and does not lead to discrimination. The provisions of the Russian Constitution provide criteria, which observance is mandatory when introducing restrictions on human and civil rights and freedoms. However, no state of emergency was introduced in the Russian Federation. The state has adopted the self-isolation regime that does not have sufficient legal regulation. It has created legal uncertainty. The legal basis of measures to restrict freedom of movement is questionable. It seems these measures go beyond the high-alert regime and require the adoption of regulations that meet the requirements of legislation in the field of emergency situations. The realization of the right to health requires a solution to the problem of coordinating the needs of other patients and patients with COVID-19.Conclusions. Based on the analysis of international law, the law of foreign states and lawmaking activities of state authorities of the Russian Federation in the context of the spread of coronavirus, the authors conclude that the created legal framework for regulating the current situation is characterized by inconsistency, lack of «transparency» and radicality. Unfortunately, the pandemic has shown that regulation in sphere of emergencies, as well as health care, was not fully prepared for active spread of coronovirus. It is necessary to ensure that all emergency measures, including the imposition of a state of emergency, are lawful, proportionate, necessary and non-discriminatory, with a specific purpose and duration

Реализация прав человека в условиях пандемии COVID-19

The subject of the article is the legal basis of human rights and freedoms, including their restriction as one of the aspects of the COVID-19 pandemic. The purpose of the research is to confirm or confute the hypothesis that the restriction of human rights in particular the right to life, the right to health and freedom of movement in Russia during COVID-19 pandemic is legally justified.The methodology of research includes the formal legal interpretation of legal acts as well as the comparative analysis of Russian and foreign legal literature. The authors analyze and interpret international law, including international treaties and the law of foreign states as well as law of the Russian Federation and the constituent entities of the Russian Federation.The main results. Restrictive measures of main human rights may lead to the violation of the constitutional rights and freedoms of citizens, and can also create conditions for abuse of authority while applying the rules governing the emergency situations. International human rights law allows the suspension of certain rights in an emergency that threatens the life of the nation. This can only be done in cases where the emergency has been officially declared, the adoption of emergency measures is caused by an urgent need in the current situation, does not contradict other obligations under international law, is limited in time and does not lead to discrimination. The provisions of the Russian Constitution provide criteria, which observance is mandatory when introducing restrictions on human and civil rights and freedoms. However, no state of emergency was introduced in the Russian Federation. The state has adopted the self-isolation regime that does not have sufficient legal regulation. It has created legal uncertainty. The legal basis of measures to restrict freedom of movement is questionable. It seems these measures go beyond the high-alert regime and require the adoption of regulations that meet the requirements of legislation in the field of emergency situations. The realization of the right to health requires a solution to the problem of coordinating the needs of other patients and patients with COVID-19.Conclusions. Based on the analysis of international law, the law of foreign states and lawmaking activities of state authorities of the Russian Federation in the context of the spread of coronavirus, the authors conclude that the created legal framework for regulating the current situation is characterized by inconsistency, lack of «transparency» and radicality. Unfortunately, the pandemic has shown that regulation in sphere of emergencies, as well as health care, was not fully prepared for active spread of coronovirus. It is necessary to ensure that all emergency measures, including the imposition of a state of emergency, are lawful, proportionate, necessary and non-discriminatory, with a specific purpose and duration.Рассматривается реализация прав и свобод человека, в том числе в контексте их ограничения, как один из аспектов пандемии COVID-19. Особое внимание уделяется праву на жизнь, праву на здоровье и свободу передвижения. На основе анализа международного права, права зарубежных государств, а также соответствующей нормотворческой деятельности российских федеральных и региональных органов государственной власти в условиях распространения новой коронавирусной инфекции делается вывод, что созданная правовая база по регулированию сложившейся ситуации характеризуется противоречивостью, отсутствием «прозрачности» и радикальностью

Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric oxide synthesis in patients with arterial hypertension

,d Objectives Insufficient production and/or increased decomposition of the potent endogenous vasodilator nitric oxide plays an important role in development and progression of arterial hypertension and its complications. One of the most effective means of stimulating endogenous nitric oxide synthesis is controlled adaptation to hypoxia. This study examined the effect of a 20-day, intermittent, normobaric intermittent hypoxia conditioning (IHC) program on blood pressure (BP) and nitric oxide production in patients with stage 1 arterial hypertension. Methods The IHC sessions consisted of four to 10 cycles of alternating 3-min hypoxia (10% FIO 2 ) and 3-min room air breathing. BP was monitored for 24 h before and after IHC, and nitric oxide synthesis was evaluated by 24-h urinary excretion of the stable nitric oxide metabolites nitrate and nitrite. Results IHC increased nitric oxide synthesis and decreased BP in hypertensive patients to values similar to those of normotensive individuals. Significant inverse correlations were found between nitric oxide production and disease duration, SBP, and DBP. Moreover, IHC enhancement of nitric oxide synthesis was especially robust in patients with arterial hypertension of more than 5 years duration. The reduction in BP persisted for at least 3 months in 28 of 33 hypertensive patients. Conclusion IHC exerted a robust, persistent therapeutic effect and can be considered as an alternative, nonpharmacological treatment for patients with stage 1 arterial hypertension. The antihypertensive action of IHC is associated with normalization of nitric oxide production

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)

Background Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. Methods and results Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines). Conclusions The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world

РЕНТГЕНОСПЕКТРАЛЬНЫЙ АНАЛИЗ КРОВИ БЕЗ ОТДЕЛЕНИЯ ОРГАНИЧЕСКОЙ СОСТАВЛЯЮЩЕЙ

The possibility of X-ray spectral analysis of blood and plasma without separation of organic component has been investigated. The organic components influence has been calculated as total H, C, N, S determination by elemental analysis method. O and Na has been determined by electron probe microanalysis, elements more heavy then Mg – by X-ray fluorescence microanalysis.Keywords: X-ray spectral analysis, matrix effects, non-analysis elements, blood, plasma, biological materials.(Russian)DOI: http://dx.doi.org/10.15826/analitika.2013.17.2.003O.I. Lyamina1, T.A. Kupriyanova1, I.P. Stolyarov1, M.N. Filippov1, A.A.Viryus2 1Kurnakov Institute of General and Inorganic Chemistry of Russian Academy of Science, Moscow, Russia 2 Institute of Experimental Mineralogy of Russian Academy of Sciences, Chernogolovka, Moscow region, Russian Federation Исследована возможность рентгеноспектрального анализа крови и плазмы крови без предварительного отделения органической составляющей. Учет влияния органической матрицы осуществлен путем определения общего содержания H, C, N и S методом органического элементного анализа, O и Na определены методом электронно-зондового рентгеноспектрального микроанализа, элементы, начиная с Mg, - методом локального рентгенофлуоресцентного анализа.Ключевые слова: рентгеноспектральный анализ, матричные эффекты, неопределяемые элементы, кровь и ее составляющие, биологические объекты.DOI: http://dx.doi.org/10.15826/analitika.2013.17.2.00

Features of the functional activity of macrophage link of immunity with gastroesophageal reflux disease depending on the type of reluctate: in vitro model

Aim. A generalized analysis of changes in functional activity of macrophages on the basis of phagocytic activity, cytokine profile, changes in the level of expression of surface markers characteristic of pro - or anti-inflammatory phenotype of the cells when exposed to reluctate. Materials and methods. Developed in vitro model of co-peritoneal macrophages of mice With57/BL6 (n=65) and reluctate patients with gastroesophageal reflux disease (GERD; n=65) having different pH values (three group comparison). Took into account the standard criteria phagocytic ability (absorption Staphylococcus aureus 9198, light microscopy), secretory activity (cytokine profile Th1/Th2, flow cytometry) and receptor characterization of macrophages (expression of CD25/80/163/206, flow cytometry). Results. The phagocytic activity of macrophages, calculated on the basis of the average number of bacteria ingested by one phagocyte, is not associated with the pH value of the added reluctate. It is established that the alkalinisation of reluctate leads to significant alteration in the expression of CD receptors - decrease M1 and increase M2. The index of total production of Th1/Тһ2 in groups progressively decreased with increasing pH of reluctate and amounted to 3.6 units in the group pH from 4.6 to 6.6; 2.8 units group a pH of 6.7-7.2 and 1.6 units in the group pH of 7.3 to 8.1, due to increased production of Th2 cytokines at offset reluctate pH to slightly alkaline side. The data obtained indicate the increase of expression and secretion of anti-inflammatory markers at an alkaline pH shift of reluctate. Analysis of the studied characteristics of the activity profile of macrophages in the proposed in vitro model justifies the need for considering the peculiarities of the functional activity of macrophages under the influence of reluctate different nature. The special importance of studying the cytokine profile and characteristics of the functional activity of macrophages in patients with GERD, given the nature of reluctate

Функциональные ответы альвеолярных макрофагов, сурфактантный белок D и заболевания легких

Functions of alveolar macrophages and surfactant protein D in lung disease.Функциональные ответы альвеолярных макрофагов, сурфактантный белок D и заболевания легких