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

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

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

Practical efficacy and safety of Konsilar D24 in patients with hypertension: data from the KONSONANS program

Aim. In practice, to evaluate the efficacy, safety and long-term adherence to therapy with a fixed-dose combination of ramipril/indapamide (Konsilar-D24) in patients with grade 1-2 hypertension (HTN) who have not achieved blood pressure (BP) control with prior therapy or have not taken antihypertensive therapy.Material and methods. This multicenter open-label observational program included 524 patients with grade 1-2 HTN who did not take antihypertensive therapy or did not reach the target BP level with mono or dual antihypertensive therapy, as well as patients shifted to Konsilar-D24 therapy no later than two weeks before the start of the program. All patients signed a written informed consent to participate in the program. The safety analysis set includes all patients who have taken at least one dose of a fixed-dose combination of ramipril/indapamide and have visited physician at least once during the program. The effectiveness analysis set included all patients in the safety population who completed the study in accordance with protocol (n=511). Clinical systolic blood pressure (SBP), diastolic BP (DBP) and heart rate were assessed at baseline, as well as at 0,5, 1, 3 and 6 months of treatment. A post hoc subgroup analysis of changes in BP and heart rate was performed depending on age, sex and baseline body mass index.Results. The fixed-dose combination of ramipril with indapamide significantly reduced SBP and DBP after 2-week treatment (-20,9±10,1 mm Hg; pConclusion. Despite the limitations inherent in observational studies, the KONSONANS program has demonstrated high efficacy and safety of fixed-dose combination of ramipril/indapamide taken once a day in hypertensive patients. Ramipril/indapamide fixed-dose combination therapy significantly improved BP control and achieved even lower individual target BP levels in the majority of hypertensive patients

ОТЛОЖЕНИЯ ТАНХОЙСКОГО ТРЕТИЧНОГО ПОЛЯ, ЮЖНОБАЙКАЛЬСКАЯ ВПАДИНА: СТРАТИГРАФИЯ, КОРРЕЛЯЦИИ И СТРУКТУРНЫЕ ПЕРЕСТРОЙКИ В БАЙКАЛЬСКОМ РЕГИОНЕ

Biostratigraphic and lithofacial studies of sediments in the Tankhoi Tertiary field, which evolution reflects transformations of the terrain in the Baikal region at the Oligocene-Miocene, Early-Middle Miocene, Miocene-Pliocene and Early-Late Pliocene transitions. The main part of the field is composed of clastic molassoids formed during 'early orogen' stage in the coastal part of an extensive paleobasin with a slow water current and in shallow lakes of the Mishikha-Klyuevka and Osinovka river paleobasins that formed, respectively, at the Oligocene-Miocene and Early-Middle Miocene boundaries. In the Miocene, as suggested by analyses of malacofauna and diatoms, South Baikal was a major, quite deep paleolake. These water bodies were related in the Miocene as evidenced by the partial similarity of diatom species found in South Baikal and the Tunka valley, as well as the presence of similar endemic fauna species in the sediments. Accumulated coarse, mainly proluvial-alluvial deposits are indicators of the tectonic activity that resulted in a dramatic ‘late orogen’ increase of contrasting features of the regional terrain.Выполнены биостратиграфические и литолого-фациальные исследования осадочных отложений Танхойского третичного поля, в формировании которого отражены перестройки рельефа Прибайкалья, происходившие на рубежах олигоцена–миоцена, раннего–среднего миоцена, миоцена–плиоцена и раннего–позднего плиоцена. Основная часть поля сложена тонкообломочными молассоидами, сформировавшимися на «раннеорогенном» этапе в слабопроточной береговой части обширного палеобассейна и в мелких озерах–старицах Мишихинско-Клюевской и Осиновской речных палеодолин, заложившихся, соответственно, на рубежах олигоцена–миоцена и раннего–среднего миоцена. Из результатов анализа малакофауны и диатомовых водорослей следует, что Южный Байкал представлял собой в миоцене крупное и достаточно глубокое палеоозеро. Частичная общность диатомовых видов Южного Байкала и Тункинской долины, а также присутствие сходной эндемичной фауны в отложениях свидетельствуют о связи миоценовых водоемов этих территорий. Тектоническая активизация, повлекшая за собой резкое «позднеорогенное» увеличение контрастности рельефа, обозначилась накоплением грубообломочных преимущественно пролювиально-аллювиальных отложений.

ДИНАМИЧЕСКОЕ ИССЛЕДОВАНИЕ КЛИНИКО-ИММУНОЛОГИЧЕСКИХ ПОКАЗАТЕЛЕЙ У БОЛЬНЫХ С ВПЕРВЫЕ ВЫЯВЛЕННЫМ САРКОИДОЗОМ

Cytokine profile in bronchoalveolar lavage fluid (BALF) and blood serum was investigated in 80 patients with newly diagnosed sarcoidosis. Of them, 42 patients were treated with prednisolone and 38 patients were treated with fenspirid (Eurespal). BALF interleukin (IL) concentration was higher than serum IL concentration that could reflect a local immune response. To the 6th month of the therapy, significant blood levels of IL-2, IL-4 and IL-5 in prednisolone-treated patients were found compared to fenspirid-treated patients that could indicate an increased immune Tx-2 activity that, in turn, could facilitate development of prednisolone adverse effects. Treatment with fenspirid during 6 months has led to increased production of IL-10 that was 2.5-fold higher compared to IL-10 level in prednisolone-treated patients. The results suggest more effective inhibition of excessive immune inflammation in prednisolone-treated patients.Выполнено исследование цитокинового профиля в бронхоальвеолярном лаваже (БАЛ) и сыворотке крови у пациентов (n = 80) с впервые выявленным саркоидозом. Пациенты 1-й группы (n = 42) получали преднизолон, 2-й (n = 38) – фенспирид (эреспал). Отмечено, что содержание интерлейкинов (IL) в БАЛ выше, чем в сыворотке крови, что является отражением местного иммунного ответа. По сравнению с пациентами группы лечения эреспалом значительный уровень продукции в сыворотке крови IL-2, IL-4 и IL-5 к 6-му месяцу лечения преднизолоном указывает на повышенную активность иммунологического ответа по типу Тх-2, что может оказывать влияние на побочные реакции лечения преднизолоном. Лечение эреспалом в течение 6 мес. приводит к повышению продукции IL-10, что в 2,5 раза выше аналогичного показателя в группе преднизолона. Это свидетельствует о более эффективном подавлении избыточного иммунологического компонента воспаления в результате проводимой терапии