Presence Of Endothelial Dysfunction Research Articles

Oxidative stress–induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk

BackgroundCardiovascular events represent a major cause of non–graft-related death after liver transplant. Evidence suggest that chronic inflammation associated with a remarkable oxidative stress in the presence of endothelial dysfunction and procoagulant environment plays a major role in the promotion of thrombosis. However, the underlying molecular mechanisms are not completely understood. ObjectivesIn order to elucidate the mechanisms of posttransplant thrombosis, the aim of the present study was to investigate the role of oxidation-induced structural and functional fibrinogen modifications in liver transplant recipients. MethodsA case-control study was conducted on 40 clinically stable liver transplant recipients and 40 age-matched, sex-matched, and risk factor–matched controls. Leukocyte reactive oxygen species (ROS) production, lipid peroxidation, glutathione content, plasma antioxidant capacity, fibrinogen oxidation, and fibrinogen structural and functional features were compared between patients and controls. ResultsPatients displayed enhanced leukocyte ROS production and an increased plasma lipid peroxidation with a reduced total antioxidant capacity compared with controls. This systemic oxidative stress was associated with fibrinogen oxidation with fibrinogen structural alterations. Thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in patients compared with controls. Moreover, steatotic graft and smoking habit were associated with high fibrin degradation rate. ConclusionROS-induced fibrinogen structural changes might increase the risk of thrombosis in liver transplant recipients.

Endothelial Dysfunction is Related to Central Retinal Artery Occlusion

Objective: Central retinal artery occlusion (CRAO) is severe and painless vision loss due to retinal infarction. Most CRAO patients have atherosclerotic risk factors. Flow-mediated dilatation (FMD) and pulse wave velocity (PWV) may indicate the presence or progression of atherosclerosis. This study aims to evaluate the arterial stiffness parameters and the presence of endothelial dysfunction in patients with CRAO. Materials and Methods: 33 consecutive CRAO patients (63 ± 7 years, 21 men (63.6%)) were recruited in the study. 35 age /sex-matched participants were included as a control group, FMD and PWV were measured from the brachial artery, as indicators of endothelial dysfunction and atherosclerosis in the arterial wall, respectively. Additionally, the transthoracic echocardiographic parameters of the patients were investigated. Results: CRAO patients had significantly higher frequencies of hypertension, hyperlipidemia, and smoking status. Furthermore, the frequency of diabetes was also higher in the CRAO group, but the difference was not statistically significant. CRAO patients had significantly higher PWV and lower FMD compared to the controls. There were no significant differences between groups regarding left ventricle systolic and diastolic functions. Conclusion: Our study showed that CRAO patients may have endothelial dysfunction and increased arterial stiffness. Systemic endothelial dysfunction and atherosclerosis may be linked to the development of CRAO.

ROS-Driven Structural and Functional Fibrinogen Modifications Are Reverted By JAK Inhibition in Myeloproliferative Neoplasms

Myeloproliferative neoplasms (MPNs) are bone marrow diseases characterized by excess clonal hematopoiesis resulting in elevated peripheral blood counts. Subtypes include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). They share clinical features (e.g., splenomegaly, thrombotic complications, risk of leukemic transformation), and a common molecular basis: the dysregulation of the JAK-STAT pathway, which confers a hypersensitivity of hematopoietic stem cells (HSC) to the action of growth factors and cytokines, and, as a result, an overproduction of blood cells. Genetic analysis of patients with MPNs revealed that >95% of patients with PV and about 50% of patients with ET or PMF carry an activating point mutation in the JAK2 gene (JAK2-V617F). Despite clinical evidence indicating a higher susceptibility of MPN patients to develop thrombotic disease, the underlying pathogenetic mechanisms are not fully understood. It appears that thrombosis is the result of a severe inflammatory response associated to remarkable oxidative stress in the presence of endothelial dysfunction and a procoagulant environment. Hypercoagulability is a consequence of disrupted hemostasis and fibrinolysis due to damage of the endothelium and defective fibrinolysis. Evidence suggests that overproduction of ROS and a deprived antioxidant system play a major role in the pathogenesis of MPN, as well as in the resistance to tyrosine-kinase inhibitor therapy. Moreover, systemic inflammation is thought to be the main trigger of thrombosis and seems to be mainly mediated by pro-inflammatory cytokines along with endothelial cell dysfunction. Recent studies have provided evidence that fibrinogen plays a multifaceted role in inflammatory responses and autoimmunity. The ability of fibrinogen to participate in the inflammatory response depends on its specific interaction with integrins, the leukocyte cell surface adhesion receptors expressed on neutrophils, monocytes, macrophages, and several subsets of lymphocytes. In MPN patients, endothelial cell dysfunction, increased reactive oxygen species (ROS) production, and proinflammatory cytokines have been reported, together with impaired fibrinolysis. We also investigated the potential role of oxidative stress and inflammation in the promotion of thrombosis. In order to study the mechanisms of inflammation-induced thrombosis in MPN patients, the aim of the present study was to investigate the role of oxidation-induced structural and functional fibrinogen modifications in MPN patients. The eventual counteracting effects of ruxolitinib, a first-in-class JAK inhibitor, were also assessed. 40 MPN patients and 40 age- and sex-matched healthy control subjects were included in the study. We measured specific oxidative stress markers andtheir modifications in plasma, and functional and structural parameters in purified fibrinogen fractions. Marked signs of oxidative stress in plasma (P<0.01 versus controls) and, correspondingly, an increased extent of fibrinogen oxidation (P<0.01 versus controls) were observed in patients. Furthermore, fibrinogen fractions purified from MPN patients exhibited significantly reduced clotting ability and decreased susceptibility to plasmin-induced lysis (P<0.01 versus controls). Alterations in fibrinogen secondary structure, as suggested by circular dichroism spectroscopy, and in fibrin clot architecture were also identified. Importantly, clot structure obtained by stimulated emission depletion (STED) super-resolution microscopy indicated modifications in fiber diameter and clot porosity in MPN patients (P<0.01 versus controls). In patient samples, fibrinogen clot analysis and oxidative-dependent changes reveal novel structural and functional fibrinogen modifications which may favor thrombotic complications in MPNs. In patients receiving ruxolitinib, a significant improvement in redox status was observed, accompanied by a significant improvement in fibrinogen structural and functional features, suggesting a potential impactof ruxolitinib on cardiovascular prevention in MPNs.

The endothelial functional is impaired by advanced glycation end products (AGE) in eutrophic and obese healthy adults

Background: An endogenous increase in advanced glycation products (AGE - advanced glycation end product) has been correlated with coronary artery disease (CAD) for some time, but the role of exogenous AGEs consumed through foods with any degree of processing that involves temperature increase, has not yet been fully elucidated. We aimed to verify if the dietary intake of AGE (dAGE) and the formation of fluorescent AGE in the skin correlate with the presence of endothelial dysfunction and subclinical atherosclerosis during the aging process. Design: Observational, quantitative, descriptive cross-sectional study Methods: 30 adults (age 54 + 9.7 years; non-smokers, without diabetes mellitus (DM), and without coronary artery disease were stratified by Body Mass Index (BMI) range (normal weight <25 Kg/m2, between 25 and 29.9 Kg/m2 overweight and obesity >30 Kg/m2), and evaluated about dietary intake and AGE formation and cardiovascular parameters related to endothelial function, and subclinical atherosclerosis. We used Carotid Doppler Ultrasound to calculate intimal medial thickness (IMT), flow-mediated dilation (FMD) to verify endothelial function, Skin Autofluorescence (SAF) AGE reading to measure AGE formation. We collected 03 24-hour dietary recalls on different days to calculate dietary AGE intake. Results: dAGE and SAF was homogeneous in the 3 evaluated groups (eutrophic = 17743 + 6088 kU/day ; 3,0 + 0,7 AU , overweight = 20555 + 4901 kU/day ; 2,7 + 0,5 AU, obese = 18424 + 8778 kU/day; 2,7 + 0,7 AU; p=0.63; p=0,58). dAGE was inversely correlated with the FMD in the eutrophic group (r=-0.679, p<0.05). SAF was inversely orreated with FD in the obesegroup (r=-0,662, p= <0,05). Conclusion: In healthy elderly, higher dietary AGE and the fluorescent AGE in the skin are independently associated with endothelial dysfunction, suggesting a contribution to the atherosclerosis process.

Severe COVID-19 classified by SCRI is associated with higher levels of AOPP and 8- OHDG.

SARS-CoV-2 has become one of the most important and challenging medical research topics in recent years. The presence of endothelial dysfunction, immune thrombosis, and oxidative stress contributes to complications and requires more extended hospitalisation of patients. In this article, we focused on analysing the impact of oxidative stress on the severity of COVID-19 infection. The study group consisted of 72 patients with laboratory-confirmed SARS-CoV enrolled. The patients were divided into moderate and severe diseases according to the SCRI (Simple Covid Risk Index, including lymphocyte/D-dimer ratio). Using the ELISA kit, we determined the level of AOPP and 8-OHdG. Patients with severe COVID-19 had higher levels of both AOPP (P<0.05) and 8-OHdG (P<0.05) compared to patients with moderate disease. Albumin levels were significantly lower (P<0.001), although fibrinogen (P<0.01), D-dimer (P<0.001), and TF (P<0.05) levels were higher in severe patients than in moderate course. AOPP/Alb was also higher among severe patients (P<0.05). Our data suggest a potential role for AOPP and 8-OHdG in predicting the outcome of SARS-CoV-2 patients. Elevated AOPP levels were associated with increased Dimer-D, TF, and vWF activity levels.

Endothelial dysfunction in patients with non-alcoholic fatty liver disease

Purpose of the study: The aim of the studyis to study the vascular response in response to a test of reactive hyperemia in patients with NAFLD and to identify the relationship of fatty liver damage with endothelial dysfunction. Methods: The study was conducted on the basis of the Irkutsk Regional Order of the Badge of Honor Clinical Hospital, the Angarsk City Clinical Hospital No. 1 and the Consultative and Diagnostic Department No. 1 of the Irkutsk Regional Infectious Diseases Clinical Hospital. Object of study: patients with NAFLD and practically healthy volunteers. All respondents underwent indirect elastometry to diagnose liver fibrosis, and to assess endothelial dysfunction, a sample of reactive hyperemia according to the Celermajer method [15]. Statistical analysis of the data obtained was performed in the program Statistica 13 for Windows. Results: The study was conducted in the period 2014-2016. Examined 64 people aged 25 to 64 years with a confirmed diagnosis of NAFLD and 23 practically healthy volunteers aged 25 to 44 years included in the clinical comparison group. Conclusions: 1. Fibrous changes in the liver were more common among middle-aged people and were more pronounced than among younger people; 2. The correlation of fatty liver damage with endothelial dysfunction was revealed - the greater the degree of fibrosis, the stronger the pathological reaction of the vascular wall; 3. The presence of endothelial dysfunction in steatosis has been proven, and, accordingly, the risk of cardiovascular events. Conclusion: the results obtained indicate the connection of pathological processes: liver damage in NAFLD and the development of CVD.

Судинні порушення у хворих на ревматичні хвороби після перенесеного COVID-19

The article briefly summarizes data on the role of micro- and macrocirculatory disorders in the pathogenesis of COVID-19. Focused attention on similarities of clinical and pathogenetic features of rheumatic diseases, COVID-19 and its complications. The review analyzed and compared the data of the assessment of the main instrumental studies of the functional state of blood vessels in patients with rheumatic diseases in general and in patients with rheumatic diseases who suffered from COVID-19 (capillaroscopy and occlusion test). A conclusion was made about the presence of endothelial dysfunction in rheumatic diseases and its features in patients with rheumatic diseases after transmission of COVID-19. This leads to the opinion about the expediency of timely detection of secondary disorders of the functional state of blood vessels in patients with rheumatic diseases who are convalescents of COVID-19, and justifies the use of an occlusion test for this purpose. No conflict of interests was declared by the authors.

Coronary flow velocity reserve is reduced in patients with an exaggerated blood pressure response to exercise.

Coronary artery disease and cardiovascular mortality are increased in patients with an exaggerated blood pressure response to exercise. The exact cause of this increase remains unknown, but previous studies have indicated the presence of endothelial dysfunction in peripheral arteries and subclinical atherosclerosis in these patients. The present study aimed to clarify whether coronary microvascular dysfunction is also present in patients with exaggerated blood pressure response to exercise. A total of 95 patients undergoing exercise testing were consecutively enrolled. Flow-mediated vasodilatation and carotid intima-media thickness were measured using standardized methods. A transthoracic echocardiography examination was performed to measure coronary flow velocity reserve. Patients with an exaggerated blood pressure response to exercise had significantly lower coronary flow velocity reserve than the controls (2.06 (1.91-2.36) vs. 2.27 (2.08-2.72), p = 0.004), and this difference was caused by a reduction in hyperemic flow velocity (57.5 (51.3-61.5) vs. 62.0 (56.0-73.0), p = 0.004) rather than a difference in basal flow (26.5 (22.3-29.8) vs. 26.0 (24.0-28.8), p = 0.95). Patients with an exaggerated blood pressure response to exercise also had a significantly greater carotid intima-media thickness and significantly lower flow-mediated vasodilatation than controls. However, an exaggerated blood pressure response to exercise remained a significant predictor of coronary microvascular dysfunction after adjusting for confounders (OR: 3.60, 95% CI: 1.23-10.54, p = 0.02). Patients with an exaggerated blood pressure response to exercise show signs of coronary microvascular dysfunction, in addition to endothelial dysfunction and subclinical atherosclerosis. This finding might explain the increased risk of coronary artery disease and cardiovascular mortality in these patients.

An Imidazoline 2 Receptor Ligand Relaxes Mouse Aorta via Off-Target Mechanisms Resistant to Aging.

Imidazoline receptors (IR) are classified into three receptor subtypes (I1R, I2R, and I3R) and previous studies showed that regulation of I2R signaling has neuroprotective potential. In order to know if I2R has a role in modulating vascular tone in health and disease, we evaluated the putative vasoactive effects of two recently synthesized I2R ligands, diethyl (1RS,3aSR,6aSR)-5-(3-chloro-4-fluorophenyl)-4,6-dioxo-1-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole -1-phosphonate (B06) and diethyl [(1-(3-chloro-4-fluorobenzyl)-5,5-dimethyl-4-phenyl-4,5-dihydro-1H-imidazol-4-yl]phosphonate] (MCR5). Thoracic aortas from Oncins France 1 (3- to 4-months-old) and C57BL/6 (3- to 4- and 16- to 17-months-old mice) were mounted in tissue baths to measure isometric tension. In young mice of both strains, MCR5 induced greater relaxations than either B06 or the high-affinity I2R selective ligand 2-(2-benzofuranyl)-2-imidazoline (2-BFI), which evoked marginal responses. MCR5 relaxations were independent of I2R, as IR ligands did not significantly affect them, involved activation of smooth muscle KATP channels and inhibition of L-type voltage-gated Ca2+ channels, and were only slightly modulated by endothelium-derived nitric oxide (negatively) and prostacyclin (positively). Notably, despite the presence of endothelial dysfunction in old mice, MCR5 relaxations were preserved. In conclusion, the present study provides evidence against a functional contribution of I2R in the modulation of vascular tone in the mouse aorta. Moreover, the I2R ligand MCR5 is an endothelium-independent vasodilator that acts largely via I2R-independent pathways and is resistant to aging. We propose MCR5 as a candidate drug for the management of vascular disease in the elderly.

Imaging Assessment of Endothelial Function: An Index of Cardiovascular Health.

Endothelial dysfunction is a key early mechanism in a variety of cardiovascular diseases and can be observed in larger conduit arteries as well as smaller resistance vessels (microvascular dysfunction). The presence of endothelial dysfunction is a strong prognosticator for cardiovascular events and mortality, and assessment of endothelial function can aid in selecting therapies and testing their response. While the gold standard method of measuring coronary endothelial function remains invasive angiography, several non-invasive imaging techniques have emerged for investigating both coronary and peripheral endothelial function. In this review, we will explore and summarize the current invasive and non-invasive modalities available for endothelial function assessment for clinical and research use, and discuss the strengths, limitations and future applications of each technique.

Impaired Endothelial Function in Convalescent Phase of COVID-19: A 3 Month Follow Up Observational Prospective Study.

Background: Endothelial dysfunction has a role in acute COVID-19, contributing to systemic inflammatory syndrome, acute respiratory distress syndrome, and vascular events. Evidence regarding COVID-19 middle- and long-term consequences on endothelium are still lacking. Our study aimed to evaluate if COVID-19 severity could significantly affect the endothelial function after three months from the acute phase. Methods: We assessed endothelial function in outpatients with previous COVID-19 three months after negative SARS-CoV-2 molecular test by measuring flow-mediated dilation (FMD) in patients categorized according to a four-variable COVID-19 severity scale (“home care”; “hospital, no oxygen”; “hospital, oxygen”; “hospital requiring high-flow nasal canula, non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation”). FMD difference among COVID-19 severity categories was assessed with analysis of variance; we further clarified the relationship between FMD and previous COVID-19 severity with multivariate logistic models. Results: Among 658 consecutive COVID-19 subjects, we observed a significant linear trend of FMD reduction with the increase of the COVID-19 category (p < 0.0001). The presence of endothelial dysfunction was more frequent among hospitalized patients (78.3%) with respect to home-care patients (21.7%; p < 0.0001). COVID-19 severity was associated with increased endothelial dysfunction risk (OR: 1.354; 95% CI: 1.06–1.71; p = 0.011) at multivariate binary logistic analysis. FMD showed a significant direct correlation with PaO2 (p = 0.004), P/F ratio (p = 0.004), FEV1 (p = 0.008), and 6MWT (p = 0.0001). Conclusions: Hospitalized COVID-19 subjects showed an impaired endothelial function three months after the acute phase that correlated with pulmonary function impairment. Further studies are needed to evaluate if these subjects are at higher risk of developing pulmonary disease or future cardiovascular events.

Endothelial function and adaptive capabilities of adolescent adolescents with arterial hypertension

Summary. The article is devoted to the study of the state of vascular reactivity, morphofunctional parameters of the heart and adaptive capabilities in adolescents with arterial hypertension. The goal is to study the the state of endothelium-dependent vasodilation and determine the adaptive capabilities of boys with arterial hypertension without metabolic risk factors, depending on the presence of endothelial dysfunction. The study included 22 boys with arterial hypertension aged 13-17 years, 10 of them had endothelial dysfunction on a sample with reactive hyperemia. The study included clinical examination, anthropometry, ECG, EchoCG, functional tests (Ruffier, klinoorthotest). Serum total cholesterol levels were also assessed. Statistical analysis was performed using the program s / n SPSS 17 4a 180844250981. Results. It was found that 58.4% of boys with arterial hypertension had endothelial dysfunction without metabolic risk, which in most cases combined with reduced exercise tolerance and insufficient physical activity. In such adolescents, in comparison with peers with hypertension and normal endothelial function, higher growth, a high frequency of dolichomelia, an increase in the ejection fraction and pressure in the left atrium are noted, indicating an increase in the pumping function of the left ventricle. The frequency of registration of endothelial dysfunction was not substantially correlated with the type of vegetative support for activities in children with arterial hypertension. However, in 60% it was registered against insufficient sympathoadrenal supply - asympathicotonic and hyperdiastolic variants of the klinoorthotest. The presence of endothelial dysfunction is recorded in more than half of adolescents with arterial hypertension. Higher ejection fraction and pressure in the left atrium during systole, which are determined in patients with arterial hypertension and insufficient vasodilation with a decrease in heart rate reflect adaptive changes in the functioning of the myocardium with a deterioration in endothelial function.

Діагностична та прогностична значущість судинної молекули міжклітинної адгезії-1 (sVCAM-1) у дітей із бронхіальною астмою

З метою вивчення рівня судинної молекули міжклітинної адгезії-1 (sVCAM-1) у дітей із бронхіальною астмою на різних етапах захворювання нами обстежено 69 дітей віком від 6 до 17 років, які страждають від персистуючої бронхіальної астми, в період загострення та ремісії та 15 практично здорових дітей групи контролю. Проводили манжетову пробу та визначали рівень S-нітрозотіолу в сироватці крові для оцінки функції ендотелію. Вивчали рівень sVCAM-1 у сироватці крові імуноферментним методом. Установлено наявність ендотеліальної дисфункції у всіх дітей, хворих на бронхіальну астму. Відмічено значне підвищення рівня sVCAM-1 у сироватці крові як у період загострення, так і в період ремісії захворювання, що свідчить про триваючий вплив на ендотелій та формування стійкого хронічного запалення.

Особливості добового профілю артеріального тиску у хворих на цукровий діабет залежно від ендотеліальної дисфункції

Актуальність. Цукровий діабет (ЦД) — захворювання, що супроводжується оксидативним стресом, хронічним неспецифічним запаленням, пошкодженням судинної стінки, ендотеліальною дисфункцією. Особливістю перебігу артеріальної гіпертензії у хворих на ЦД є більш раннє формування діабетичної хвороби нирок (ДХН). Сьогодні здійснюється пошук маркерів ендотеліальної дисфункції, що дозволять виявляти ДХН на ранніх стадіях, коли зміни в нирках потенційно оборотні. Метою роботи було дослідити показники добового профілю артеріального тиску у хворих на ЦД та визначити їх взаємозв’язки з показниками швидкості клубочкової фільтрації й ендотеліальної функції за рівнем показників TGF-β1 (transforming growth factor beta-1 — трансформуючий фактор росту бета-1) та VCAM-1 (vascular cell adhesion molecule 1 — васкулярна молекула судинної адгезії 1). Матеріали та методи. У дослідження включені 124 хворі на ЦД, із них 66 пацієнтів із ЦД 1-го типу, 58 — із ЦД 2-го типу. Результати. Рівні показників ендотеліальної функції TGF-β1 та VCAM-1 у хворих на ЦД 1-го та 2-го типів кількісно залежали від показника швидкості клубочкової фільтрації. Між показниками ендотеліальної функції TGF-β1, VCAM-1 та показниками добового моніторування артеріального тиску виявлені сильні та середньої сили кореляційні зв’язки, у зв’язку з чим комплекс показників добового моніторування артеріального тиску та наявність ендотеліальної дисфункції можна вважати ранніми ознаками прогресування ДХН. Висновки. Для добового профілю артеріального тиску у хворих на ЦД на ранніх стадіях діабетичної нефропатії характерне вірогідне порушення циркадних ритмів. Недостатнє нічне зниження артеріального тиску у хворих на ЦД 1-го та 2-го типу характеризує наявність прогресування діабетичної нефропатії за показниками добового індексу артеріального тиску.

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction

BackgroundSome studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age.AimsThe aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices.MethodsWe enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection.Results63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance.DiscussionPatients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

Hemostasis system and uterine scar formation in women undergoing conservative myomectomy

Annotation. The aim of the study was to assess the characteristics of hemostasis and the formation of a scar on the uterus in women who underwent conservative myomectomy. Medical records of 426 women with a scar on the uterus were analyzed. The results of pathomorphological examination of biopsy materials obtained in the area of the “old” scar during myomectomy with recurrence of fibroids with a gestational age of 33 to 40 weeks. The micromorphological structure of postoperative scars and pericycatric region of the myometrium was determined and immunohistochemical examination was performed on serial paraffin sections of biopsy material using primary and secondary monoclonal antibodies of Dako kits (USA). To quantify the immunohistochemical results in the sections, the number of cells in which the immunoperoxidase label (positive staining) was detected in 10 fields of view randomly selected (&gt;200 cells) was counted. FW expression was determined using a semi-quantitative method with H-score calculation. Statistical processing of the obtained results was performed by non-parametric methods using the software TIBCO Statistica 13.5 (USA). It was shown that 40.1% of uterine scars are due to conservative myomectomy. In the postoperative period, patients who underwent conservative myomectomy have a tendency to hypercoagulation, while the frequency of thromboembolic complications after conservative myomectomy does not exceed 3%. High FW expression indicates the presence of endothelial dysfunction and should be taken into account when assessing the risk of thromboembolic complications in patients after conservative myomectomy.

Study of association of urine albumin to creatinine ratio with endothelial dysfunction in HIV patients on HAART

Background: In HIV (Human immunodeficiency virus) positive patients several factors have been proposed to explain the cardiovascular (CV) risk, which include pro-athero-thrombotic viral effect, infection-mediated immune dysfunction and possible effects of HAART(Highly active antiretroviral therapy). Presence of endothelial dysfunction, an early CV risk marker, in HIV-infected patients on long-term HAART. Endothelial dysfunction can be measured by bFMD (Brachial artery flow mediated vasodilatation). Urine albumin to creatinine ratio (UACR) is frequent in HIV patients and is predictor of cardiovascular risk. UACR and endothelial dysfunction are positively associated in HIV affected patients thereby increased UACR might help to identify endothelial dysfunction in HIV patients on HAART.&#x0D; Aims and Objectives: • To measure urine albumin to creatinine ratio in HIV patients on HAART. • To find out correlation between UACR and bFMD.&#x0D; Materials and Methods: Study was conducted on HIV Patients admitted to hospital, considering the inclusion and exclusion criteria. Detailed clinical history, examination and Blood investigations were done. Endothelial function was assessed by brachial artery flow mediated vasodilatation(bFMD).&#x0D; Results: Among 100 HIV patients, 14% had UACR &lt;30 and 86% had UACR &gt;30 and mean UACR is 90 ±06. Mean BFMD was 8.44 ± 7.65. We identified a significant Negative correlations were found between bFMD and UACR(r=- 0.832, P=&lt;0.001).&#x0D; Conclusion: Use of urine albumin to creatinine ratio (UACR) as a routine screening tests in those who are HIV positive on HAART can be used to find out those cases of HIV who are progressing towards cardiovascular impairment so that newer approaches can be used in them to prevent further cardiovascular involvement.

ASSESSMENT OF ENDOTHELIAL DYSFUNCTION IN PREGNANT WOMEN WITH OBESITY AND PREECLAMPSIA

The aim: To assess the values of endothelial vascular growth factor (VEGF) in blood serum and circulating endothelial microparticles CD32+CD40+ in the peripheral blood of pregnant women depending on the severity of obesity and presence of preeclampsia. Materials and methods: the study included 122 pregnant women divided into groups in accordance with their height and weight parameters and presence of preeclampsia. We studied the serum VEGF concentration by enzyme-linked immunosorbent assay, carried out the count of CD32+CD40+ circulating endothelial microparticles in the peripheral blood by using flow cytometry. Results: It has been found out the serum VEGF concentration in pregnant women with obesity decreases with rising level of obesity and the preeclampsia manifestation. In contrast to the decrease in this marker, there is an increase in the number of circulating endothelial microparticles CD32+CD40+ in the peripheral blood of pregnant women with obesity and preeclampsia. This pattern of these indicators points out the presence of endothelial dysfunction, which may contribute to occurrence of preeclampsia in pregnant women with concomitant obesity. Conclusions: The indicators of VEGF concentration and the count of circulating endothelial microparticles CD32+CD40+ in the blood serum can serve as reliable markers for evaluating the severity of endothelial dysfunction in pregnant women with concomitant obesity and preeclampsia.

Is Willebrand Factor Indicative of Chronic Inflammation in Children with Asthma?

To improve our knowledge and to understand how the level of von Willebrand factor indicates the development of chronic inflammation in children with recurrent wheezing and asthma. It was a prospective cohort study. This study was conducted in children with recurrent wheezing and asthma who were referred to a children's hospital during 2017-2018. Patients were divided into 3 groups depending on the number of episodes of wheezing. Patients were examined for von Willebrand factor levels at admission and after treatment. Data analysis was performed with Statsofta Statistica Version 8 (Tulsa, OK). WF1 levels in Group 2 and 3 children statistically significantly increased in comparison with the control group (p<0.001). WF2 levels remained elevated only in Group 3 patients (p<0.001). WF2 levels in Group 1 and 2 decreased to the indices of the control group (p>0.05). The WF2 significantly decreased after treatment in Group 2 children (p=0.0000, T=0) and Group 3 (p=0.0000, T=0). levels of Willebrand factor indicate the presence of endothelial dysfunction. The level of Willebrand factor in the peak period of wheezing depends on the number of episodes of wheezing in history. Persistent high rates of Willebrand factor, even after the relief of clinical symptoms, indicates the present of chronic inflammation and can be regarded as the formation of asthma in children.

SOME FEATURES OF THE PATHOGENESIS OF ALCOHOLIC HEPATITIS AND ALCOHOLIC CIRRHOSIS OF THE LIVER IN COMBINATION WITH ARTERIAL HYPERTENSION

Purpose - to study the features of the combined course of chronic alcoholic hepatitis (CAH) and alcoholic liver cirrhosis (ALC) with arterial hypertension (AH) by determining the main clinical and laboratory parameters. Material and methods. 13 patients with CAH (group I), 22 patients with CAH in combination with arterial hypertension (group II), 22 patients with ADC (group III) and 40 patients with ADC in combination with arterial hypertension (group IV) were examined. Serum content of C-reactive protein, tumor necrosis factor-α (TNFα), transforming growth factor-β1 (TGFβ1 ), interleukin-10 (IL-10), 8-isoprostane, D-dimer, stable metabolites of nitric oxide (nitrites / nitrates), endothelin-1 (ET-1), intercellular adhesion molecules-1 (ICAM-1); plasma recalcification time (PRT), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), plasma fibrinogen levels, antithrombin III (ATIII) activity, factor XIII activity, platelet aggregation. Liver function and blood lipid spectrum were also examined. Results. It was found that the manifestations of cytolysis and cholestasis syndromes were mostly more pronounced in patients with alcoholic liver disease (ALD) due to its combination with hypertension. At the same time, there was an increase in the levels of CRP, TNFα, TGFβ1 , IL-10, ceruloplasmin and 8-isoprostane. In the presence of concomitant hypertension, the content of IL-10 (in patients with CAH), CRP (in patients with ALC), as well as the content of 8-isoprostane and ceruloplasmin (in patients with CAH and AlC) probably (p &lt;0.05) exceeded that in patients without hypertension. At the same time, in both CAH and ALC, the presence of endothelial dysfunction was established. Disorders of the endothelial functional state were accompanied by changes in the hemocoagulation of homeostasis and the blood lipid spectrum. When evaluating the quality of the LAL test, it was found that the positive test was in 97.5% of patients with ALC with hypertension compared with CAH with hypertension, where this test was positive in 68.2% of cases. When comparing groups of patients with ALC and CAH, it was found that in 77.2% of cases it was positive in group III and in 38.5% - in group I. In patients with ALC with and without hypertension, this test had the following distribution: 39 patients out of 40 had a positive test in group IV and 17 out of 22 - in group III. Conclusion. The occurrence of cytolytic, cholestatic, mesenchymal-inflammatory syndromes and hepatocellular insufficiency in patients with ALD with hypertension is associated with the direct action of ethanol on the liver, the development of systemic inflammation, oxidative stress, dyslipoproteinemia, endothelial dysfunction with hemocoagulation disorders and endotoxemia..