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© 2021 Elsevier Ltd Objectives: Metabolic syndrome (MetS) and its components (high blood pressure, BMI≥30, altered fasting glucose, low HDL cholesterol and high triglycerides) may undermine early perioperative outcomes after radical prostatectomy (RP). We tested this hypothesis. Materials & methods: Within the National Inpatient Sample database (2008–2015) we identified RP patients. The effect of MetS was tested in four separate univariable analyses, as well as in multivariable regression models predicting: 1) overall complications, 2) length of stay, 3) total hospital charges and 4) non-home based discharge. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. Results: Of 91,618 patients: 1) 50.2% had high blood pressure, 2) 8.0% had BMI≥30, 3) 13.0% had altered fasting glucose, 4) 22.8% had high triglycerides and 5) 0.03% had low HDL cholesterol. Respectively, one vs. two vs. three vs. four MetS components were recorded in 36.2% vs. 19.0% vs. 5.5% vs. 0.8% patients. Of all patients, 6.3% exhibited ≥3 components and qualified for MetS diagnosis. The rates of MetS increased over time (EAPC:+9.8%; p < 0.001). All four tested MetS components (high blood pressure, BMI≥30, altered fasting glucose and high triglycerides) achieved independent predictor status in all four examined endpoints. Moreover, a highly statistically significant dose-response was also confirmed for all four tested endpoints. Conclusion: MetS and its components consistently and strongly predict early adverse outcomes after RP. Moreover, the strength of the effect was directly proportional to the number of MetS components exhibited by each individual patient, even if formal MetS diagnosis of ≥3 components has not been met.

© 2020 Biosensors based on nanotechnology are developing rapidly and are widely applied in many fields including biomedicine, environmental monitoring, national defense and analytical chemistry, and have achieved vital positions in these fields. Novel nano-materials are intensively developed and manufactured for potential biosensing and theranostic applications while lacking comprehensive assessment of their potential health risks. The integration of diagnostic in vivo biosensors and the DDSs for delivery of therapeutic drugs holds an enormous potential in next-generation theranostic platforms. Controllable, precise, and safe delivery of diagnostic biosensing devices and therapeutic agents to the target tissues, organs, or cells is an important determinant in developing advanced nanobiosensor-based theranostic platforms. Particularly, inspired by the comprehensive biological investigations on the red blood cells (RBCs), advanced strategies of RBC-mediated in vivo delivery have been developed rapidly and are currently in different stages of transforming from research and design to pre-clinical and clinical investigations. In this review, the RBC-mediated delivery of in vivo nanobiosensors for applications of bio-imaging at the single-cell level, advanced medical diagnostics, and analytical detection of biomolecules and cellular activities are presented. A comprehensive perspective of the technical framework of the state-of-the-art RBC-mediated delivery systems is explained in detail to inspire the design and implementation of advanced nanobiosensor-based theranostic platforms taking advantage of RBC-delivery modalities.

© 2020 The Authors Background: Since the first report by Perry et al. (1955), most studies affirmed the hypertensive effects of cadmium (Cd) in humans. Nonetheless, conclusions between studies remain inconsistent. Objective: The aim of this study was to reevaluate the evidence for a potential relationship between Cd exposure and altered blood pressure and/or hypertension, focusing on studies published between January 2010 and March 2020. Methods: We reviewed all observational studies from database searches (PubMed and SCOPUS) on Cd exposure and blood pressure or hypertension. We extracted information from studies that provided sufficient data on population characteristics, smoking status, exposure, outcomes, and design. Results: Thirty-eight studies met our inclusion criteria; of those, twenty-nine were cross sectional, three case control, five cohort and one interventional study. Blood or urinary Cd levels were the most commonly used biomarkers. Conclusions: A positive association between blood Cd levels and blood pressure and/or hypertension was identified in numerous studies at different settings. Limited number of representative population-based studies of never-smokers was observed, which may have confounded our conclusions. The association between urinary Cd and blood pressure and/or hypertension remains uncertain due to conflicting results, including inverse relationships with lack of strong mechanistic support. We point to the urgent need for additional longitudinal studies to confirm our findings.

© 2020 The Authors Background: Since the first report by Perry et al. (1955), most studies affirmed the hypertensive effects of cadmium (Cd) in humans. Nonetheless, conclusions between studies remain inconsistent. Objective: The aim of this study was to reevaluate the evidence for a potential relationship between Cd exposure and altered blood pressure and/or hypertension, focusing on studies published between January 2010 and March 2020. Methods: We reviewed all observational studies from database searches (PubMed and SCOPUS) on Cd exposure and blood pressure or hypertension. We extracted information from studies that provided sufficient data on population characteristics, smoking status, exposure, outcomes, and design. Results: Thirty-eight studies met our inclusion criteria; of those, twenty-nine were cross sectional, three case control, five cohort and one interventional study. Blood or urinary Cd levels were the most commonly used biomarkers. Conclusions: A positive association between blood Cd levels and blood pressure and/or hypertension was identified in numerous studies at different settings. Limited number of representative population-based studies of never-smokers was observed, which may have confounded our conclusions. The association between urinary Cd and blood pressure and/or hypertension remains uncertain due to conflicting results, including inverse relationships with lack of strong mechanistic support. We point to the urgent need for additional longitudinal studies to confirm our findings.

© 2020, Springer Healthcare Ltd., part of Springer Nature. Introduction: The relationship between blood pressure (BP) and cerebral blood flow (CBF) is not fully understood. This study evaluated the impact of a perindopril arginine/indapamide (Pa/I) single-pill combination (SPC) on CBF in middle-aged patients. Methods: A total of 22 treatment-naïve patients with essential hypertension and at least one hypertension-mediated organ damage and 41 healthy controls were enrolled. At baseline, all participants underwent brain magnetic resonance imaging (MRI); patients with hypertension underwent an additional MRI at end of follow-up. Arterial spin labeling (ASL) was used to calculate CBF in the frontal lobe cortical plate. Patients with hypertension received once-daily Pa/I 5 mg/1.25 mg SPC, which could be increased to Pa/I 10 mg/2.5 mg at 2 weeks if necessary. Patients with hypertension underwent 24-h ambulatory BP monitoring (ABPM) at baseline and end of follow-up. Results: Mean baseline BP values were 146.2/93.1 and 119.1/76.1 mmHg in the hypertension and control groups, respectively. Patients with hypertension had significantly (p < 0.001) lower CBF in the cortical plate of both left (36.2 ± 8.3 vs. 45.3 ± 3.5 ml/100 g/min) and right (37.9 ± 7.9 vs. 45.8 ± 3.2 ml/100 g/min) frontal lobes compared to normotensive controls. At the end of follow-up, there was a statistically significant (p < 0.001) increase in CBF in the cortical plate of both left (from 36.2 ± 8.3 to 47.5 ± 9.8 ml/100 g/min) and right frontal lobes (from 37.9 ± 7.9 to 47.4 ± 10.1 ml/100 g/min) compared to baseline. No significant difference was found between end of follow-up CBF levels in frontal lobes of patients with hypertension and those of healthy controls at baseline. Office BP decreased by 24.2/15.5 mmHg and 24-h ABPM from 145.5/95.3 to 120.8/79.3 mmHg. Conclusion: In middle-aged, treatment-naïve patients with hypertension, Pa/I SPC was associated with increased CBF in the cortical plate of the frontal lobes, which achieved levels of normotensive controls. The increase in CBF had no clear association with observed BP changes. Registration number: ISRCTN67799751.

© 2019 Rad51 is a key protein in DNA repair by homologous recombination and an important target for development of drugs in cancer therapy. 4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) has been used in clinic during the past 30 years as an inhibitor of anion transporters and channels. Recently DIDS has been demonstrated to affect Rad51-mediated homologous pairing and strand exchange, key processes in homologous recombination. Consequently, DIDS has been considered as a potential revertant of radio- and chemo-resistance of cancer cells, the major causes of therapy failure. Here, we have investigated the behavior of DIDS towards serum albumins. The effects of environmental factors, primarily, solvent polarity, on DIDS stability were evaluated, and the mechanisms of interaction of DIDS with human or bovine serum albumin were analyzed using isothermal calorimetry, circular dichroism and fluorescence spectroscopies. DIDS interaction with both serum albumins have been demonstrated, and the interaction characteristics have been determined. By comparing these characteristics for several DIDS derivatives, we have identified the DIDS moiety essential for the interaction. Furthermore, site competition data indicate that human albumin has two DIDS-binding sites: a high-affinity site in the IIIA subdomain and a low-affinity one in the IB subdomain. Molecular docking has revealed the key molecular moieties of DIDS responsible for its interactions in each site and shown that the IB site can bind two ligands. These findings show that binding of DIDS to serum albumin may change the balance between the free and bound DIDS forms, thereby affecting its bioavailability and efficacy against Rad51.

© 2019 Elsevier GmbH Introduction: Eastern and North-Eastern regions of Kazakhstan are considered to be environmentally disadvantaged due to industrial pollution and activity of the former Semipalatinsk Nuclear Test Site. Ferrous metallurgy is represented by the world's largest ferroalloy plant located in Aksu. In addition to a ferroalloy plant, Aksu is the home for the largest thermal power plant in Kazakhstan. Objective: Biomonitoring of 31 hair and blood trace elements (Ag, Ba, Be, Bi, Cs, Co, Ce, Cr, Cu, Eu, Gd, Hf, In, La, Li, Mn, Mo, Nb, Nd, Pb, Sc, Sn, Tl, Th, U, V, W, Y, Yb, Zn, and Zr) in non-occupationally exposed population residing in polluted areas of East Kazakhstan and Pavlodar regions. Methods: Five case groups, residing in the vicinity to the former Semipalatinsk Nuclear Test Site (Akzhar, Borodulikha, and Karaul) or in proximity to industrial plants (Aksu and Ust-Kamenogorsk) have been assessed vs. controls from a rural settlement in Kurchum. In total, 204 hair and blood samples were analyzed by inductively coupled plasma mass spectrometry. Results: The observed blood concentrations of trace elements were in agreement with earlier studies on residents of industrially polluted areas. Elevated levels of blood Ba, Mn, Pb, V, and Zn were detected in residents of Aksu and Ust-Kamenogorsk. The elemental composition of head hair was characterized by greater stability between the study sites. Conclusion: Residency near the former Semipalatinsk Test Site could be considered as safe, while the environmental status of industrial settlements appears to be rather adverse.

© The Author(s) 2019. Responses of five rotary blood pumps, namely HeartAssist 5, HeartMate II, HeartWare, Sputnik 1, and Sputnik 2, were extensively assessed in six test cases using a mathematical model of the cardiovascular system. Data for the rotary pumps were derived from pressure–flow curves reported in the literature. The test cases were chosen to attempt to cover most common clinical conditions, such as partial or full support or transitions between different levels of ventricular support. The investigated parameters are collected in a table and presented in figures, such as pressure–volume loops, H-Q curves, pump flow, and aortic pressure waveforms. HeartAssist, Sputnik 1, and Sputnik 2 pumps provide comparable level of aortic pressure, pump flow pulsatility PI(QP), and aortic pressure pulsatility PI(AoP) due to the similarity of pressure–flow characteristic curves of these pumps. HeartMate II provides a minimal backflow among other investigated rotary blood pumps due to the maximum pressure head at zero flow. HeartWare provides minimal pulsation of flow, which is confirmed by a flow range from −2 to 7 L/min in case 1. At the same time, the greatest degree of unloading was demonstrated by the HeartWare due to the flatness of the pressure–flow curve shape. The conclusions were made based on the obtained results, including the influence of pressure–flow curve shape on the pump performance and occurrences of adverse events, such as backflow or suction. For example, the increase of the pressure head at zero flow decreases the likelihood of backflow through the pump, and with it, increasing the flow under minimal pressure head increases the likelihood of suction.

The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25-75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known.NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available.

© 2019 The Authors Background: The aim was to estimate the prevalence of harmful alcohol use in relation to socio-demographic characteristics among acutely ill medical patients, and examine identification measures of alcohol use, including the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth). Methods: A cross-sectional study, lasting one year at one hospital in Oslo, Norway and one in Moscow, Russia recruiting acute medically ill patients (≥ 18 years), able to give informed consent. Self-reported data on socio-demographics, mental distress (Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4 (AUDIT-4) and alcohol consumption past 24 h were collected. PEth and alcohol concentration were measured in whole blood. Results: Of 5883 participating patients, 19.2% in Moscow and 21.1% in Oslo were harmful alcohol users, measured by AUDIT-4, while the prevalence of PEth-positive patients was lower: 11.4% in Oslo, 14.3% in Moscow. Men in Moscow were more likely to be harmful users by AUDIT-4 and PEth compared to men in Oslo, except of those being ≥ 71 years. Women in Oslo were more likely to be harmful users compared to those in Moscow by AUDIT-4, but not by PEth for those aged < 61 years. Conclusions: The prevalence of harmful alcohol use was high at both study sites. The prevalence of harmful alcohol use was lower when assessed by PEth compared to AUDIT-4. Thus, self-reporting was the most sensitive measure in revealing harmful alcohol use among all groups except for women in Moscow. Hence, screening and identification with objective biomarkers and self-reporting might be a method for early intervention.

© 2019 Elsevier Ltd Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC. CNV was induced by laser photocoagulation in C57BL/6J mice. APC was injected intravitreally immediately or 7 days after CNV induction. Neovascularization was evaluated on RPE-choroidal flatmounts using FITC-dextran perfusion and CD31 immunofluorescence. CNV leakage was measured by fluorescein angiography (FA). The ability of APC to stabilize the RPE barrier was evaluated in-vitro by dextran permeability and zonula occludens 1 (ZO1) immunostaining. Tie2 blocking was induced in-vivo by intraperitoneal injection of Tie2 kinase inhibitor and in-vitro by incubation with anti Tie2 antibodies. APC treatment dramatically inhibited the generation of newly formed CNV leakage sites and reversed leakage in 85% of the pre-existing CNV leaking sites. In RPE cell culture, APC induced translocation of ZO1 to the cell membrane, accompanied by reduction in permeability of the monolayer. Inhibition of Tie2 significantly decreased APC protective activities in both the mouse model and the RPE cell culture. Our results show that APC treatment significantly inhibits the leakage and growth of newly formed, as well as pre-existing CNV, and its protective activities are partially mediated via the Tie2 receptor. The data suggest that APC should be further investigated as a possible effective treatment for CNV.

© 2019 Elsevier B.V. A validated approach to determine various methionine cycle metabolites (S-adenosylmethionine, S-adenosylhomocysteine, and methylthioadenosine) in human blood plasma is offered. The approach is based on solid-phase extraction (with grafted phenylboronic acid) and derivatization with chloroacetaldehyde followed by ultra-performance liquid chromatography with fluorescence detection. We used a 100 × 2.1 mm × 1.8 μm C18 column for the selective separation of analytes. Chromatographic separation was achieved with gradient elution of acetonitrile (flow rate 0.2 mL/min) from 2 to 20%. The eluent was initially composed of 10 mM KH2PO4 with 10 mM acetic acid and 25 μM heptafluorobutyric acid. The total analysis time was 11 min. Validation of the method included detection of the limit of detection (2 nM), limit of quantification (5 nM), accuracy (97.2–101%), and intra- and interday precision (2.2–9.0%). Analysis of plasma samples from healthy volunteers revealed that the average levels of S-adenosylmethionine, S-adenosylhomocysteine, and methylthioadenosine were 93.6, 20.9 and 14.8 nM, respectively.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We studied the reactions of spinal ganglion neurons accompanying regeneration of the skin wound complicated by S. aureus sp. infection. The appearance of neuron groups with different morphofunctional changes was noted: reversible dystrophic and compensatory reactions and irreversible degenerative changes. The proportion of small B neurons was higher than the proportion of large type A neurons at all terms of the experiment. Application of plateletrich plasma to the wound after preliminary hydroimpulsive treatment considerably reduced cell destruction and stimulated regenerative effects in neurons starting from day 7 of the experiment. Application of platelet-rich plasma without hydroimpulsive treatment decelerated wound regeneration and increased the number of destructively changed neurons even in comparison with spontaneous wound healing. Close correlations between protein synthesis markers and stages of the wound process and its characteristics were revealed.

© 2018 Elsevier B.V. Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy. Verapamil significantly increased the anticonvulsant effect of CBZ and reduced its effective dose by at least 30% (from 30 mg/kg to 20 mg/kg). Binding of carbamazepine to the poloxamer 188-coated PLGA nanoparticles enabled a 30-fold increase of its anticonvulsive effect, as compared to the free drug. The inhibition of Pgp did not influence the effectivity of carbamazepine encapsulated in nanoparticles.

© 2018 Pharmascope Publications. All rights reserved. To study the function of the endothelium in conducting vascular pharmacological samples in normal and blocking the synthesis of nitric oxide by ultrasound examination of the velocity of central blood flow in the femoral artery in comparison with the changes in systemic hemodynamics and the linear velocity of microcirculatory flow using laser flowmetry. It was studied the parameters of the blood flow velocity (the maximum systolic and diastolic velocity, average systolic and diastolic velocity, Gosling index of pulsatility and resistance index by the Doppler ultrasound Minimax-Doppler-K), the parameters of central circulation ("Biopac-systems MP-150", AcqKnowledge 4.2, USA), and linear velocity of the microcirculatory flow of the musculus vastus medialis (Biopac MP-150, USA) in intact animals and rats with N-Ni-tro-L-arginine methyl ester (L-NAME) induced deficiency of nitric oxide. Quantitative evaluation of endothelial dysfunction in the conduct of pharmacological tests with endothelium-dependent (acetylcholine) and endothe-lium-independent (sodium nitroprusside) vasodilatation is most indicative in calculating the coefficient reflecting the ratio of vascular responses areas in intact rats with L-NAME induced deficiency of nitric oxide. Blood flow parameters (the maximum systolic velocity, the calculated difference between systolic and diastolic velocities) showed a high correlation, both with mean arterial pressure and a linear velocity of the microcirculatory flow. We conclude, that ultrasound Doppler were reflected in the systemic and local vascular response to the administration of vasodilators. It allows an assessment of endothelial function by using the Minimax-Doppler-K device.

© 2018 IEEE. The paper presents an algorithm of system identification for implantable rotary blood pumps. The algorithm allows to build mathematical models in accordance with the quality metric introduced to assess the effectiveness of identification. The quality metric was set as an error of pump flow estimation. In the result the mathematical models were identified using experimental dataset for two different rotary blood pumps Sputnik. The identified model of Sputnik 1 characterizes by the mean error about 0.12 L on the control set, the identified model of updated pump-Sputnik 2-mean error about 0.14 L. The identified models intended for control of pump flow during in vitro trials.

© 2018 International Society for Cellular Therapy Background: Menstrual blood is only recently and still poorly studied, but it is an abundant and noninvasive source of highly proliferative mesenchymal stromal cells (MSCs). However, no appropriate isolation method has been reported due to its high viscosity and high content of clots and desquamated epithelium. Methods: We studied three different isolation approaches and their combinations: ammonium-containing lysing buffer, distilled water and gradient-density centrifugation. We tested the proliferative capacity, morphology, surface markers and pluripotency of the resulting cells. Results: Our isolation method yields up to four million nucleated cells per milliliter of initial blood, of which about 0.2–0.3% are colony-forming cells expressing standard mesenchymal markers CD90, CD105 and CD73, but not expressing CD45, CD34, CD117, CD133 or HLA-G. The cells have high proliferative potential (doubling in 26 h) and the ability to differentiate into adipocytes and osteocytes. Early endometrial MSCs (eMSCs) express epithelial marker cytokeratin 7 (CK7). CK7 is easily induced in later passages in a prohepatic environment. We show for the first time that a satisfactory and stable yield of eMSCs is observed throughout the whole menstrual period (5 consecutive days) of a healthy woman. Discussion: The new cost/yield adequate method allows isolation from menstrual blood a relatively homogenous pool of highly proliferative MSCs, which seem to be the best candidates for internal organ therapy due to their proepithelial background (early expression of CK7 and its easy induction in later passages) and for mass cryobanking due to their high yield and availability.

© 2018, Pleiades Publishing, Inc. The article presents empirical data on the possible use of transcranial Doppler sonography as a method for the identification of functional specialization of hemispheres. We investigated intrahemispheric differences in the increase in blood flow velocity indicators during the performance of cognitive tasks with verbal and nonverbal stimuli in 20 healthy right-handed participants and 20 right-handed patients with local unilateral vascular brain lesions. We observed interhemispheric and intrahemispheric differences in blood flow velocity indicators between arteries during the performance of cognitive tasks with different variants of verbal stimuli in all participants. It has been found that one of the hemispheres plays a dominant role in verbal and nonverbal stimulus processing.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. Most patients with arterial hypertension (AH) for successful long-term blood pressure (BP) control require combination of antihypertensive drugs acting on various target organs. Accumulated experience shows that about 30% of patients require combination therapy with 3 drugs from different pharmacological classes. Efficacy of BP control in real clinical practice with the use of various doses of perindopril, indapamide, and amlodipine as components of taken once-daily triple fixed combination was assessed in the 3-months prospective observational open-label PETRA study. In this study data of office BP measurements and 24-hour ambulatory BP monitoring (ABPM) were obtained from 11209 ambulatory patients (47.6% women) with AH. Initial mean office BP (BPmoff) was 156.58±16.10/91.56±9.33 mm Hg, AH duration - 9.48±7.19 years. After switching to triple fixed dose combination of perindopril, indapamide, and amlodipine BPmoff decreased by 24.81±15.47/11.41±9.90 mm Hg (p<0.0001). Doses of perindopril, indapamide, and amlodipine in combination at the final visit were 5/1.25/5, 10/2.5/5, and 10/2.5/10 mg. 24-hour ambulatory BP monitoring (ABPM) was carried out in 76 patients. Mean 24-hour BP lowed from mean 155.51±17.43/85.28±11.48 down to 134.63±12.51/77.83±8.99 mm Hg (p<0.0001). Clinically relevant improvement of a number of parameters of metabolism occurred after 3 months of the study (in particular, lowering of levels of total and low-density lipoprotein cholesterol [-8.6 and - 11.4%, respectively], triglycerides [-12,1%], fasting blood glucose [-6.6%]). Thus, results of the PETRA study confirmed 24-hour long antihypertensive efficacy of triple fixed dose combination of perindopril, indapamide, and amlodipine. This drug combination can present novel possibility in treatment of patients with AH who have not achieved target BP values on preceding dual combination therapy and fully corresponds with the single pill concept for formation of adherence to therapy.

© 2018 Stolichnaya Izdatelskaya Kompaniya. The metabolic syndrome is a highly prevalent condition associated with increased cardiovascular risk in the population. Microvasculature is the terminal part of the cardiovascular system which primarily reacts to the increased secretion of the pro inflammatory adipokines typical for the metabolic syndrome. Microcirculation and blood cell abnormalities are the leading mechanisms of cardiovascular events development in this condition. Prevalence of microcirculation abnormalities and red blood cell dysfunction in metabolic syndrome and their role in the increased blood viscosity and cardiovascular events development are covered by the paper. The microcirculation abnormalities with a special focus on red blood cell dysfunction (impaired aggregation, stiffness) seen in metabolic syndrome and associated conditions are discussed in detail. The impact of abnormal red blood cell deformability (secondary to cholesterol accumulation in the cellular membranes) on the hemorheological abnormalities is revealed. Abnormal red blood cell surface charge due to proinflammatory changes associated with insulin resistance in diabetes mellitus is highlighted. These abnormalities lead to increased red blood cell aggregation and plasma viscosity that are the essential components of cardiovascular events pathogenesis. Their timely diagnosis is crucial for effective cardiovascular prevention.