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

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

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.

Нарушение функционального фенотипа альвеолярных макрофагов при действии факторов риска хронической обструктивной болезни легких: возрастная и генетическая предрасположенность

Summary. A definitive role of tobacco smoking as a risk factor for development of chronic obstructive pulmonary diseases (COPD) is of no doubt today. We performed in vivo experimental modeling of COPD in mice of different genetic strains (С57 and Balb/c). We studied phenotypes of main cells of the innate immunity that are alveolar macrophages, and revealed genetic and age susceptibility to COPD in experimental animals. We showed that 1) there is a certain genetic susceptibility to hazardous exposition of tobacco smoke, probably, associated with proinflammatory М1 macrophage phenotype; 2) aging promotes transformation of macrophage phenotypes towards antiinflammatory М2 which is more expressed in mice macro-phages with baseline genetically determined М1 phenotype (mice strain С57), and 3) long-time exposition to tobacco smoke enhances age-dependent macrophage transformation aside М2 phenotype, that is also more expressed in mice macrophages with genetically determined М1 phenotype (С57).Резюме. Роль табакокурения как фактора риска в развитии хронической обструктивной болезни легких (ХОБЛ) является определяющей. В эксперименте in vivo проводилось моделирование ХОБЛ у мышей разных генетических линий (С57 и Balb/c). Изучены фенотипы основных клеток системы врожденного иммунитета легких – альвеолярных макрофагов. Выявлены генетическая и возрастная предрасположенности к развитию ХОБЛ у экспериментальных животных. Показана определенная генетическая предрасположенность к воздействию табачного дыма, возможно, связанная с провоспалительным М1-фенотипом макрофагов. Установлено, что увеличение возраста способствует трансформации фенотипа макрофагов в сторону противовоспалительного М2-фенотипа, более выраженного в макрофагах мышей с исходно генетически детерминированным М1-фенотипом (линия С57), а при длительном вдыхании табачного дыма усиливается возрастная трансформация макрофагов в сторону М2-фенотипа, также более выраженная в макрофагах мышей с генетически детерминированным М1-фенотипом (линия С57)

Euro+Med-Checklist Notulae, 13

This is the thirteenth of a series of miscellaneous contributions, by various authors, where hitherto unpublished data relevant to both the Med-Checklist and the Euro+Med (or Sisyphus) projects are presented. This instalment deals with the families Amaryllidaceae (incl. Alliaceae), Apocynaceae, Caryophyllaceae, Chenopodiaceae, Compositae, Crassulaceae, Cucurbitaceae, Gramineae, Hydrocharitaceae, Iridaceae, Labiatae, Liliaceae, Malvaceae, Meliaceae, Myrtaceae, Orobanchaceae, Oxalidaceae, Papaveraceae, Pittosporaceae, Primulaceae (incl. Myrsinaceae), Ranunculaceae, Rhamnaceae, Rubiaceae, Solanaceae and Umbelliferae. It includes new country and area records and taxonomic and distributional considerations for taxa in Allium, Anthemis, Atriplex, Centaurea, Chasmanthe, Chenopodium, Delphinium, Digitaria, Elodea, Erigeron, Eucalyptus, Hypecoum, Leptorhabdos, Luffa, Malvaviscus, Melia, Melica, Momordica, Nerium, Oxalis, Pastinaca, Phelipanche, Physalis, Pittosporum, Salvia, Scorzoneroides, Sedum, Sesleria, Silene, Spartina, Stipa, Tulipa and Ziziphus, new combinations in Cyanus, Lysimachia, Rhaponticoides and Thliphthisa, and the reassessment of a replacement name in Sempervivum

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