EFFECTS OF ACUTE PHYSICAL EXERCISE OF VARYING INTENSITY ON LIPID METABOLISM IN MIDDLE AGED MEN

Aim. To investigate effects of acute physical exercise of varying intensity on lipid metabolism in middle aged men.Material and methods. Two bouts of physical exercise of moderate and high intensity were performed in 54 clinically healthy men aged 30-45 y.o. without obesity with subsequent assessment of lipid profile (total cholesterol, high density lipoprotein cholesterol, triglyceride levels, and atherogenic index). Effect of physical exercise on the lipid profile as studied both in the whole group and in subjects with and without insulin resistance.Results. Acute physical exercise of moderate and high intensity produced beneficial effects on lipid parameters (increase in cholesterol of high density lipoprotein level and reduction of atherogenic index). Increased intensity of physical exercise caused more prominent improvement of lipid profile in subjects without insulin resistance. However subjects with insulin resistance had weaker response to physical exercise than individuals without insulin resistance did and increased intensity of physical exercise did not cause significant improvement of lipid parameters in subjects with insulin resistance.Conclusion. Response to moderate or high intensive physical exercise may depend on baseline metabolic profile. It should be taken into account under development of preventive programs for modifying risk factors of cardio-vascular diseases and type 2 diabetes mellitus

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Modern Approaches to Optimal Antithrombotic Therapy for Stable Ischemic Heart Disease

The article highlights the practical aspects of the use of antithrombotic therapy in patients with stable (chronic) coronary artery disease (САD). The САD verification using modern functional and anatomical diagnostic methods are considered. Patients with stable САD represent a heterogeneous group, having various clinical scenarios. Information is provided on the main risk factors for ischemic and hemorrhagic complications that determine the choice of optimal antithrombotic therapy regimens. Modern views on the monotherapy and clopidogrel in САD are presented. The data of the largest international studies CHARISMA and PEGASUS-TIMI 54 on the use of double antiplatelet therapy in patients with stable IHD reflected in modern guidelines are highlighted. Features of new antiplatelet agents (prasugrel and ticagrelol) are described. Based on the results of the COMPASS study, indications for the administration of small doses of rivaroxaban in combination with aspirin for the secondary prevention of cardiovascular complications in patients with stable manifestations of atherosclerosis with a low risk of bleeding are considered. The use of antithrombotic therapy is associated with an increased risk of bleeding and particularly with gastrointestinal bleeding. The information on the use of drugs for the prevention of gastrointestinal bleeding is provided.Antithrombotic therapy can reduce the risk of complications associated with atherothrombosis, however, to improve prognosis a multipurpose intervention is required, including correction of risk factors and the use of drugs from different groups with proven effectiveness. Optimal medical therapy, including antithrombotic drugs, is vital for patients with САD and can successfully prevent adverse outcomes

DIFFERENTIAL DIAGNOSIS OF MYOCARDIAL DAMAGE IN REVERSIBLE DILATION OF THE CARDIAC CHAMBERS

The paper describes a case of a 46-year-old patient who has applied as having heart failure signs in the presence of enlarged cardiac chambers.A follow-up shows a favorable outcome with complete normalization of cardiac chamber sizes. Laboratory and instrumental findings (electrocardiograms, chest X-ray films, echocardiograms) are given. The possible reversible causes of dilated cardiomyopathy are discussed.</p

DIFFERENTIAL DIAGNOSIS OF MYOCARDIAL DAMAGE IN REVERSIBLE DILATION OF THE CARDIAC CHAMBERS

The paper describes a case of a 46-year-old patient who has applied as having heart failure signs in the presence of enlarged cardiac chambers.A follow-up shows a favorable outcome with complete normalization of cardiac chamber sizes. Laboratory and instrumental findings (electrocardiograms, chest X-ray films, echocardiograms) are given. The possible reversible causes of dilated cardiomyopathy are discussed

Diagnosis of familial hypercholesterolemia in children: cascade screening from theory to practice

Aim. To conduct a cascade screening and to assess its effectiveness in the diagnosis of familial hypercholesterolemia (FH) in children.Material and methods. The study was conducted from January 2017 to August 2018 on the basis of the City Clinical Hospital № 7 and the Children’s Republican Clinical Hospital (Kazan, the Republic of Tatarstan). It consisted of identifying index cases — primary patients with FH with further examination of first- and second-degree relatives &lt;18 years old. In adults, the diagnosis was established according to Dutch Lipid Clinic Network (DLCN) criteria): FH was diagnosed with a score of ≥6. In children and adolescents &lt;6 years of age, the Simon Broome Registry criteria were used.Results. During this period, 2542 case histories of patients with cardiovascular diseases were analyzed, of which 1220 people with a total cholesterol &gt;5 mmol/L were selected. Next, a targeted screening was carried out aimed at the diagnosis of FH, as a result of which 61 index patients were identified. At the next stage, as a part of cascade screening, 87 first- and second-degree relatives &lt;18 years old were examined. In 43 (49,4%) children, heterozygous HF was diagnosed, of which in 4 patients the disease was detected by re-examination after 1 year.Conclusion. Cascade screening is a necessary and effective method for the diagnosis of АР in first- and second-degree relatives &lt;18 years old. All children of the index patients should be monitored or genetic testing necessary to rule out FH. Today, it is important to increase awareness among clinicians about the diagnosis of FH in adults and children

ESTIMATION OF THE THICKNESS OF THE INTIMA-MEDIA COMPLEX IN CHILDREN WITH FAMILIAL HYPERCHOLESTEROLEMIA

Objective: to evaluate the diagnostic significance of measuring the thickness of the intima-media complex (IMC) in children with autosomal dominant familial hypercholesterolemia for early diagnostics and prompt treatment of atherosclerosis.Materials and methods. The study included 109 children – 64 children with familial hypercholesterolemia and 45 healthy children. Both groups were divided into 2 subgroups according to the age – from 3 to 8 years and from 9 to 18 years. We measured the intimamedia thickness (IMT) of the common carotid artery in all the children. To evaluate IMT we used an ultrasound scanner HD11XE (Philips, USA) with a linear (3–12MHz) sensor IMT.Results. We found a statistically significant difference (p=0.012) of the IMT of the common carotid artery in children with familial hypercholesterolemia (0.61 ± 0.02 mm) in comparison with the control group (0.49±0.02 mm), starting from the age of 9 years. There were no sex differences of IMT in patients older than 9 years.Conclusion. We found that children with familial hypercholesterolemia have higher values of IMT already from the age of 9 as compared with healthy children; the increase in TCIM is an additional criterion for the early diagnostics of atherosclerosis and evaluation of cardiovascular risk. These results emphasize the relevance of lipid-lowering therapy for patients with familial hypercholesterolemia in childhood, before the first signs of atherosclerosis appear

Use of statins in children with familial hypercholesterolemia

Familial hypercholesterolemia Is the most common genetic disease in the world. It is characterized by an increase in the level of total cholesterol and low-density lipoproteins since childhood. It is desired to diagnose and start treatment in childhood prior to development of complications, such as aortic stenosis, atherosclerotic changes in the artery walls. Statins are recommended as the first-line medications. However, due to limited experience, the clinicians have different opinions regarding the age of initiation of hypolipidemic therapy. The article is aimed to critically examine the data on the use of statins in children with familial hypercholesterolemia, their effectiveness and safety available in the world literature

Modular nanotransporters: a versatile approach for enhancing nuclear delivery and cytotoxicity of Auger electron-emitting 125I.

UNLABELLED: BACKGROUND: This study evaluates the potential utility of a modular nanotransporter (MNT) for enhancing the nuclear delivery and cytotoxicity of the Auger electron emitter 125I in cancer cells that overexpress the epidermal growth factor receptor (EGFR). METHODS: MNTs are recombinant multifunctional polypeptides that we have developed for achieving selective delivery of short-range therapeutics into cancer cells. MNTs contain functional modules for receptor binding, internalization, endosomal escape and nuclear translocation, thereby facilitating the transport of drugs from the cell surface to the nucleus. The MNT described herein utilized EGF as the targeting ligand and was labeled with 125I using N-succinimidyl-4-guanidinomethyl-3-[125I]iodobenzoate (SGMIB). Membrane binding, intracellular and nuclear accumulation kinetics, and clonogenic survival assays were performed using the EGFR-expressing A431 epidermoid carcinoma and D247 MG glioma cell lines. RESULTS: [125I]SGMIB-MNT bound to A431 and D247 MG cells with an affinity comparable to that of native EGF. More than 60% of internalized [125I]SGMIB-MNT radioactivity accumulated in the cell nuclei after a 1-h incubation. The cytotoxic effectiveness of [125I]SGMIB-MNT compared with 125I-labeled bovine serum albumin control was enhanced by a factor of 60 for D247 MG cells and more than 1,000-fold for A431 cells, which express higher levels of EGFR. CONCLUSIONS: MNT can be utilized to deliver 125I into the nuclei of cancer cells overexpressing EGFR, significantly enhancing cytotoxicity. Further evaluation of [125I]SGMIB-MNT as a targeted radiotherapeutic for EGFR-expressing cancer cells appears warranted