Insulin resistance in obesity: pathogenesis and effects

The prevalence of obesity in the world is described as the global epidepic. Being not only a chronic recurrent disease but also a serious risk factor, obesity leads to the development and aggravation of many non-communicable diseases. Excessive amount and adipose tissue dysfunction in obesity determines the risk of the development of type 2 diabetes, arterial hypertension, atherosclerosis, non-alcoholic fatty liver disease etc. Secondary insulin resistance often underlies the development of the above mentioned conditions. The mechanisms contributing to the development of insulin resistance in case of excessive adipose tissue accumulation are being intensively investigated over the last decades, however many questions yet remain unsolved. In this article we present the key mechanisms underlying insulin resistance in obesity and diagnostic approaches for insulin resistance as well as the current data in this topic. The authors review the close links between insulin resistance and obesity related diseases, namely disorders of carbohydrate metabolism, dyslipidemia, arterial hypertension, coronary artery disease and reproductive disorders

Pharmacological correction of immune disorders in patients with chronic heart failure and ischemic heart disease

Currently, there are few data on the effect of cardiovascular drugs on the immune status of patients with heart failure (HF). This paper provides information on the impact of ß-adrenergic blocking agent (BAB), angiotensin-converting enzyme inhibitors (ACEI) on the maintenance of markers of immune inflammation in the blood, as well as on inhibition of synthesis of tumor necrosis factor-α (TNF-α) and on blocking of interaction between TNF-α and membrane receptor

In Vitro and in Silico Liver Models: Current Trends, Challenges and Opportunities

Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using liver on a chip devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. Impediments to the development of liver on a chip technology include the problems with standardization of cells, limitations imposed by culturing and the necessity to develop more complicated fluidic contours. Fortunately, recent breakthroughs in the development of cell-based reporters, including ones with fluorescent label, permits monitoring of the behavior of the cells embed into the liver on a chip devices. Finally, a set of computational approaches has been developed to model both particular toxic response and the homeostasis of human liver as a whole; these approaches pave a way to enhance the in silico stage of assessment for a potential toxicity

Impact of Gut Microbiota on the Risk of Cardiometabolic Diseases Development

Obesity is a multifactorial disease that leads to excessive adipose tissue accumulation, mainly visceral fat. Importance and prevalence of obesity has increased significantly in recent decades all over the world. Until now, the pandemic of obesity has been associated more to lifestyle changes: excessive eating and low physical activity. In recent years, special attention has been paid to studying of composition and functions of intestinal microbiota as major factor in development of obesity and related comorbidities, such as hypertension, cardiac ischemia, heart failure and others. It is proved that gut microbiota affects extraction, accumulation and consumption of energy derived from food, lipid metabolism and immune response. It is also revealed that composition of the microbiota is different in thin and obese people. Thus, study of the relationship between intestinal microbiota composition and risk factors for cardiovascular diseases, in particular obesity, is an actual task. The purpose of this review is analyzing of literature about assessment of relationship between composition and functions of intestinal microbiota in the diagnostics, prevention and treatment of obesity and cardiovascular diseases

Epidemiologic features of non-alcoholic fatty liver disease in Russia

Aim of investigation. To estimate prevalence nonalcoholic fatty liver disease (NAFLD) with assessment of age dynamics of distribution, interrelation of stages and value of clinical cardio-vascular markers in patients addressing for medical aid to physicians of polyclinics of Russia.Material and methods. First Russian epidemiologic observational study DIREG L 01903 on prevalence of non-alcoholic fatty liver disease was carried out in the Russian Federation in 2007. Overall 30 754 patients (56% of women, 44% of men) in the age of 18 to 80 years who sought medical attention of municipal polyclinics irrespective of the reference reason (either with subjective symptoms of liver disease or in the absence of those) have been investigated in 208 large medical centers for 8 months. Investigation included general (anthopometrical), laboratory and instrumental investigations, such as assessment of hepatites B and C markers, liver transaminases, gamma-glutamyltranspeptidase, blood lipid spectrum, glucose level, and abdominal ultrasound investigation, if required — esophagogastroduodenoscopy. In 4–6 wks at the second visit of the patient biochemical tests were repeated or supplemented with tests for alkaline phosphatase, bilirubin, albumin, gammaglobulin, serum iron.Results. The prevalence of NAFLD among adult population of the Russian Federation was 27%, including 80,3% of hepatic steatosis cases, 16,8% — nonalcoholic steatohepatitis and 2,9% — liver cirrhosis. Frequency of NAFLD detection increase by the age of 50. In the age group of 50–59 years the prevalence of disease reached the highest values, making 31,1% among the whole screened population. The impact of all studied risk factors of cardio-vascular diseases (р<0,001) has been found. The major risk factors revealed in NAFLD patients population, were systemic hypertension (69,9%), abdominal obesity (56,2%), hypercholesterolemia (68,8%).Conclusions. Prevalence of NAFLD among adult population of Russia is very high: almost every third patient who was looking for medical attention in polyclinic, has one of NAFLD-related disease entities. Metabolic syndrome and its components have been determined as leading risk factors of this disease, that once again emphasizes significance of interrelation of cardio-vascular diseases and NAFLD. Therefore, development of management approach and search of effective treatment should be carried out in two directions — for liver and cardiac diseases

XXVII Российский национальный конгресс-онлайн «Человек и лекарство»

.6–9 апреля 2020 г. в Москве состоялся XXVII Российский национальный конгресс-онлайн «Человек и лекарство». В рамках соблюдения введенных законодательных ограничений с целью предупреждения распространения коронавирусной инфекции (2019-nCoV) мероприятие проведено в форме онлайн-конференции в запланированные сроки

Obstructive sleep apnea and cardiovascular comorbidity: common pathophysiological mechanisms to cardiovascular disease

Obstructive sleep apnea (OSA) is associated with many cardiovascular and metabolic diseases. Sleep apnea causes intermittent hypoxemia, chest pressure fluctuations and a reaction from the cerebral cortex in the form of a short awakening during sleep (EEG-activation). The consequences of pathological pathways are studied in experimental models involving cell cultures, animals, and healthy volunteers. At present, the negative impact of intermittent hypoxemia on a variety of pathophysiological disorders of the heart and blood vessels (vascular tone fluctuations, thickening of the intimamedia complex in the vascular wall, direct damaging effect on the myocardium) has a great evidence base. Two other pathological components of OSA (pressure fluctuations and EEG-activation) can also affect cardiovascular system, mainly affecting the increase in blood pressure and changing cardiac hemodynamics. Although these reactions are considered separately in the review, with the development of sleep apnea they occur sequentially and are closely interrelated. As a result, these pathological pathways trigger further pathophysiological mechanisms acting on the heart and blood vessels. It is known that these include excessive sympathetic activation, inflammation, oxidative stress and metabolic dysregulation. In many respects being links of one process, these mechanisms can trigger damage to the vascular wall, contributing to the formation of atherosclerotic lesions. The accumulated data with varying degrees of reliability confirm the participation of OSA through these processes in the formation of cardiovascular disorders. There are factors limiting direct evidence of this interaction (sleep deprivation, causing similar changes, as well as the inability to share the contribution of other risk factors for cardiovascular diseases, in particular arterial hypertension, obesity, which are often associated with OSA). It is necessary to continue the study of processes that implement the pathological effect of OSA on the cardiovascular system

Adherence to antihypertensive medication in Russia: A scoping review of studies on levels, determinants and intervention strategies published between 2000 and 2017

Source at https://doi.org/10.1186/s13690-019-0366-9.Background - Arterial hypertension (HT) is common in the Russian adult population, with half of affected individuals inadequately controlled. Low adherence to medication seems likely to be a factor. We report a scoping review of studies on adherence to antihypertensive therapy (AHT) in Russia to determine the extent of research undertaken, the frequency of adherence among adults diagnosed with HT, methodologies used in the studies, and their ability to describe determinants of adherence. Methods - A scoping review of published studies that have assessed adherence to AHT in Russian HT patients searched the main Russian and international electronic databases eLIBRARY.ru, Russian Medicine, Embase, MEDLINE for full-text reports published in the Russian language between 2000 and 2017. The last search was on November 28, 2017. Among 520 reports identified, 31 were included in the review. Results - Eighteen studies assessed adherence using the 4-item Morisky Medication Adherence Scale (MMAS-4); others used bespoke questionnaires or pill counts. 25 studies assessed levels of adherence, 11 examined its determinants, and 18 examined intervention strategies. The proportion of “adherent” patients varied from 11 to 44% using the MMAS-4, from 23 to 74% when using bespoke questionnaires, and from 5 to 43% when using pill counts. Adherence was associated with sociodemographic factors, access to free drugs provided through the Medicine Assistance Scheme (MAS), use of home blood pressure (BP) monitoring, anxiety, and comorbidity. There was no evidence that adherence was associated with income or physical activity. Evidence of an association between MAS, grade of HT, or experience of hypertensive crisis was inconclusive. Various methods to improve adherence were studied including patient education (improved from 1.8 to 3.9 points, p = 0.0002 or 2.80 to 3.79 points, p < 0.0001 measured by the MMAS-4), telephone reminders (p < 0.0001), training in home BP monitoring (p < 0.05), and use of fixed-dose combinations (p < 0.05). Conclusions - The main determinants of adherence to AHT are sociodemographic characteristics, the severity of HT, and presence of comorbidity. Patient education and use of fixed-dose combinations of drugs were identified as most important for improving adherence. Most studies assessing adherence use self-reported methods so there is a need for greater use of objective methods

Perioperative Management of Patients Receiving Antithrombotic Therapy in Schemes and Algorithms

Currently, antithrombotic therapy is the basis of the pathogenetic treatment of many cardiovascular diseases, such as coronary heart disease, stroke, peripheral vascular disease, as well as mechanical heart valves, heart rhythm disturbances, venous thromboembolism. At the same time, chronic use of antiplatelet and/or anticoagulant drugs is a complicating factor in invasive and surgical procedures, as it increases the risk of bleeding. In this regard, a fundamentally important and complex question arises: how to minimize the risk of periprocedural bleeding without exposing the patient to an increased risk of ischemic and thromboembolic complications? Perioperative management of patients who take antithrombotic drugs for a long time is a complex problem that depends on many factors - the risk of surgery, anesthesia, cardiovascular risks, and the urgency of surgery. Each clinical situation should be assessed individually, collegially, with the participation of surgeons, anesthesiologists, and therapists. The introduction of a checklist into clinical practice for each planned surgical patient will allow us to calculate the individual risk of bleeding and thromboembolic complications, and provide an optimal preventive strategy for perioperative management of the patient. The algorithms and schemes presented in the article for the perioperative management of patients with non-cardiac interventions are aimed at standardizing the management of patients before non-cardiac surgical interventions, which will reduce hemorrhagic risks in the presence of the necessary antithrombotic therapy

Prognostic Significance of the Integral Index of the Alcohol Situation in Assessing Regional Differences in Mortality from Cardiovascular Diseases in the Russian Federation

Aim. To evaluate the stability of the integral index of the alcohol situation in the regions of the Russian and its prognostic significance regarding adult mortality from diseases of the circulatory system.Material and methods. The dynamics of standardized mortality rate for cardiovascular diseases (CVD) and TM in 2012 and 2018 in regions of Russia with safe and unsafe alcohol situations was analyzed. The average group mortality rate were evaluated, as well as the average rate of dynamics of the indicator reduction for the period from 2012 to 2018.Results. In 2012, differences in the rates of total mortality, as well as mortality from CSD, IHD, and CVD in regions with different levels of alcohol wellbeing were significant with a significance level of p &lt;0.05. In 2018, intergroup differences in mortality from CSD and IHD were unreliable. Differences in average mortality rates from other causes significantly differed with a significance level of p &lt;0.05. Total mortality and mortality from CVD, including individual forms, decreased in all regions, regardless of the level of alcohol well-being. The average rate of decline in mortality in the group of regions with an unfavorable situation was lower than the same indicator in regions with a favorable situation, with the exception of mortality from CVD. The most pronounced were differences between regions in the rate of decline in mortality from MI (p &lt;0.05). For the remaining causes of death, the differences were not significant.Conclusion. The hypothesis of a significant contribution of the alcohol factor to cardiovascular mortality is confirmed. In the groups of regions that differ in the integral index of the alcohol situation, significant differences were noted in the indicators of both total mortality and mortality from the main groups of cardiovascular diseases. These differences persist over time, which confirms the hypothesis that the proposed integral indicator can be used for a long-term forecast of the influence of the alcohol situation on public indicators