Servo systems with incomplete information

The problem of control design formation i

Oxidative and antioxidant changes in blood of young people with premature coronary artery disease and abdominal obesity

Aim. To study the oxidative and antioxidant blood profile in young people with premature coronary artery disease (CAD) and abdominal obesity (AO).Material and methods. The study included 169 people. The main group consisted of 47 patients diagnosed with premature (<45 years of age) CAD, while 22 of them with AO and 25 without AO. The control group included 122 people without CAD, comparable with the main group in sex, age and body mass index. Among them, there are 67 people with AO and 55 people without AO. In all examined patients, the blood levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, MDA-modified oxidized high-density lipoprotein, superoxide dismutase (SOD), glutathione peroxidase 1, and whole blood total antioxidant capacity (TAC) were determined. Statistical processing was carried out in the SPSS 13.0 program.Results. The blood TAC was 2,3 times lower in persons with CAD than in those without CAD, and amounted to 1,58 mmol of trolox. The blood level of SOD in patients with CAD was 1,16 times higher than in the group of people without CAD. The relative odds of premature CAD were associated with decreased TAC (B=-2,855; Exp(B)=0,058; 95% confidence interval (CI), 0,008-0,392; p=0,004) and increased level of SOD (B=0,105; Exp(B)=1,076; 95% CI, 1,031-1,196; p=0,006), regardless of sex, age, risk factors. Conclusion. Thus, an increased SOD and reduced TAC can be potential biomarkers for premature CAD in people under 45 years of age

Calcification markers and long-term outcomes of coronary artery bypass grafting

Aim. To assess the long-term outcomes of coronary artery bypass grafting (CABG) and their association with calcification biomarkers.Material and methods. The study included 129 men (mean age, 61,5±7,5 years) with coronary atherosclerosis who were admitted for CABG surgery. Patients were divided into 2 groups: with favorable and unfavorable (death, myocardial infarction, stroke, surgery) 5-year prognosis after surgery. Before the surgery, the blood concentrations of calcification biomarkers (osteoprotegerin, osteopontin, osteonectin and osteocalcin) were determined in all patients.Results. Long-term outcomes of myocardial revascularization were studied in 92 patients (71%). An unfavorable long-term 5-year period was identified in 28 men (30,4%). In men with an unfavorable 5-year prognosis, the blood osteocalcin level before CABG was 1,2 times higher than in men with a favorable one. Multivariate linear regression showed that the risk of a 5-year unfavorable prognosis for coronary atherosclerosis after myocardial revascularization was associated with the blood osteocalcin concentration, determined before CABG (B=0,018, R2=0,285, p=0,008).Conclusion. The data obtained indicate the relevance of continuing studies on osteocalcin, including with respect to its contribution to coronary atherosclerosis and calcification

Changes induced in mouse lipid metabolism by simultaneous impact of antisense oligonucleotide derivatives to <i>apoB</i>, <i>PCSK9</i>, and <i>apoCIII</i> mRNAs

Development of new drugs able to decrease the level of “bad” cholesterol, in particular, based on antisense oligonucleotide derivatives (ASOs), remains relevant for the patients with familial hypercholesterolemia and/or intolerant to statins. The goal of the work was to assess the changes in the lipid metabolism caused by variants of joint impact of the ASOs targeted to the mRNAs of its key genes: apoB, PCSK9, and apoCIII. Female C57BL/6J mice; nuclease-protected 13- and 20-nucleotide ASOs, and standard protocols for quantification of lipoproteins (HDL CHL, non-HDL CHL, and total CHL) and ALT in the blood serum were used in the work. The following combinations of ASOs were four times injected to the mouse caudal vein: 1) ASO to apoB, 2) ASO to apoCIII, 3) ASO to apoB and ASO to PCSK9, 4) ASO to apoB, ASO to PCSK9, and ASO to apoCIII, 5) ASO to apoB (three doses), ASO to PCSK9, and ASO to apoCIII (two doses), 6) ASO to PCSK9 and (ASO to apoCIII – only in the fourth administration). Triple weekly administration of these ASO combinations resulted in a decrease in non-HDL CHL by 25, 16, 35, 47, 60, and 7 %, respectively, as compared with the control and 1.8-, 1.5-, 1.9-, 2.4-, 3.1, and 1.24-fold higher HDL CHL/ non-HDL CHL ratio. The subsequent ASO injection with concurrent switching to a high-fat diet after 1 week resulted in a decrease in the non-HDL CHL by 28, 2, 28, 70, 33, and 49 % for ASOs (1–6), respectively, as compared with the control; the HDL CHL/non-HDL CHL ratio was 1.5-, 1.1-, 2-, 3.7-, 1.9-, and 2-fold better. The ALT concentration for all ASO combinations remained within the norm for the control animals, demonstrating the absence of any hepatotoxic effect. The best efficiency of ASOs requires selection of concentrations for single ASOs and their combinations as well as of the order and timing of administration. Thus, a new antisense approach is proposed

NEW ASPECTS OF THE USE OF PROTEIN TISSUE-SPECIFIC MARKERS IN THE ESTIMATION OF SEVERITY OF COMMUNITY-ACQUIRED PNEUMONIA

The purpose of the study was to assess the associations of proteins of pulmonary surfactants A (SP-A) and D (SP-D) with the severity of community-acquired pneumonia. Material and methods. A survey of 188 patients diagnosed with community-acquired pneumonia (CAP). The average age of the examined patients was 54.3 ± 16.5 years (M ± SD). In 102 patients (54.3 %) severe CAP was verified. All patients underwent clinical, functional, diagnostic and laboratory studies. Results and discussion. It was determined that SP-A and SP-D content was significantly higher in patients with severe CAP compared to patients with a mild course of this disease. The direct association of severe CAP with an elevated SP-AP level, directly associated with an increase in the concentration of C-reactive protein in the blood and erythrocyte sedimentation rate, have been confirmed in early studies. Using partial correlation analysis, it was established that the severe course of CAP is directly related to SP-A (r = 0.221; p = 0.003) and SP-D content (r = 0.262; p &lt; 0.001) regardless of age, smoking, and body weight. Thus, direct associations of SP-A and SP-D with a severe course of CAP reflect the high pathogenetic significance of these protective factors in infectious lung damage

Superhelical Duplex Destabilization and the Recombination Position Effect

The susceptibility to recombination of a plasmid inserted into a chromosome varies with its genomic position. This recombination position effect is known to correlate with the average G+C content of the flanking sequences. Here we propose that this effect could be mediated by changes in the susceptibility to superhelical duplex destabilization that would occur. We use standard nonparametric statistical tests, regression analysis and principal component analysis to identify statistically significant differences in the destabilization profiles calculated for the plasmid in different contexts, and correlate the results with their measured recombination rates. We show that the flanking sequences significantly affect the free energy of denaturation at specific sites interior to the plasmid. These changes correlate well with experimentally measured variations of the recombination rates within the plasmid. This correlation of recombination rate with superhelical destabilization properties of the inserted plasmid DNA is stronger than that with average G+C content of the flanking sequences. This model suggests a possible mechanism by which flanking sequence base composition, which is not itself a context-dependent attribute, can affect recombination rates at positions within the plasmid

АССОЦИАЦИИ УРОВНЯ В КРОВИ ХОЛЕСТЕРИНА ЛИПОПРОТЕИНОВ НИЗКОЙ ПЛОТНОСТИ И БИОМОЛЕКУЛ МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ У ЛЮДЕЙ 25–44 ЛЕТ

Highlights The study is devoted to the analysis of metabolic hormones and their relationship with the main risk factors for cardiovascular diseases, in particular, elevated levels of low-density lipoprotein cholesterol. The study included people under the age of 45 with active hormones. AbstractAim. To assess the relationship between the levels of LDL and metabolic hormones reflecting metabolic disorders in young people.Methods. The study included 305 people. The group 1 included 146 people with an LDL level of &lt;2.1 mmol/L, the group 2 included 159 people with an LDL level of ≥4.2 mmol/L. Serum total cholesterol (TC), triglycerides, HDL and glucose concentrations were determined by enzymatic method using Thermo Fisher Scientific kits (Finland) on a 30i KonelabPrime clinical chemistry analyzer. The calculation of concentrations of LDL was carried out according to the Friedwald formula. The levels of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, interleukin 6, insulin, leptin, monocyte chemoattractant protein-1, pancreatic polypeptide, peptide YY, tumor necrosis factor alpha were determined by multiplex analysis using the Human Metabolic Hormone V3 (MILLIPLEX) panel on a Luminex MAGPIX flow fluorimeter.Results. In the group of patients with LDL ≥4.2 mmol/L, fasting glucose disorders were much more prevalent, the average BMI (p = 0,0001) was higher, and arterial hypertension was twice as frequent (24.8% vs. 11.6%, p = 0.003) compared with the group 1. The levels of triglycerides, TC, and glucose were higher, whereas HDL level was lower in the group 2(p = 0,0001). In patients with LDL ≥4.2 mmol/L, the values of HOMA-IR and the occurrence of IR (83.8%) according to the HOMA-IR were higher compared with the group with LDL &lt;2.1 mmol/L (p = 0,0001). Statistically significant differences in the levels of the studied indicators between the groups 1 and 2 were obtained for C-peptide, GLP-1, insulin and leptin. The relative chance of having LDL≥4.2 mmol/L is associated with an increase in the level of C-peptide (OR = 2.042, 95% CI 1.209–3.449, p = 0.008) and a decrease in the level of GLP-1 (OR = 0.997, 95% CI 0.996–0.999, p = 0.001).Conclusion. An increase in LDL levels in young people is associated with disorders of lipid and carbohydrate metabolism. These data are confirmed by changes in the serum metabolic markers that characterize metabolic disorders in the human body.Основные положенияИсследование посвящено изучению метаболических гормонов и их связи с основными факторами риска сердечно-сосудистых заболеваний, в частности с повышенным уровнем холестерина липопротеинов низкой плотности. В исследование включены люди в возрасте до 45 лет с активным гормональным статусом. АннотацияЦель. Оценить связь между уровнем холестерина липопротеинов низкой плотности (ХС-ЛНП) и метаболическими гормонами, отражающих нарушения обменных процессов у молодых людей.Материалы и методы. В исследование включено 305 человек. В первую группу вошло 146 человек с уровнем ХС-ЛНП &lt;2,1 ммоль/л, во вторую группу – 159 человек с уровнем ХС-ЛНП ≥4,2 ммоль/л. Содержание общего холестерина, триглицеридов, холестерина липопротеинов высокой плотности и глюкозы в сыворотке крови определяли энзиматическим методом с использованием наборов Thermo Fisher Scientific (Финляндия) на биохимическом анализаторе Konelab Prime 30i. Вычисление значений концентрации ХС-ЛНП проводили по формуле Фридвальда. Методом мультиплексного анализа с применением панели Human Metabolic Hormone V3 (MILLIPLEX; EMD Millipore Corp., Германия) на проточном флуориметре Luminex MAGPIX (Luminex Corp., США) определяли уровни амилина, С-пептида, грелина, глюкозозависимого инсулинотропного полипептида, глюкагоноподобного пептида 1, глюкагона, интерлейкина 6, инсулина, лептина, моноцитарного хемотаксического фактора 1, панкреатического полипептида, пептида YY, фактора некроза опухолей альфа.Результаты. В группе лиц с уровнем ХС-ЛНП ≥4,2 ммоль/л зарегистрирована более высокая распространенность нарушений уровня глюкозы натощак, в два раза чаще по сравнению с первой группой чаще встречалась артериальная гипертензия (24,8 против 11,6%, p = 0,003) и определены более высокие средние значения индекса массы тела (p = 0,0001). Уровни триглицеридов, общего холестерина, глюкозы плазмы были выше, а показатель ХС-ЛВП ниже у лиц второй группы (p˂0,0001). У пациентов с уровнем ХС-ЛНП ≥4,2 ммоль/л как само значение индекса НОМА-IR, так и встречаемость инсулинорезистентности (83, 8%) в соответствии с индексом НОМА-IR были выше в сравнении с группой лиц с ХС-ЛНП &lt;2,1 ммоль/л (p˂0,0001). Статистически значимые отличия в уровнях изучаемых показателей между группами получены для С-пептида, глюкагоноподобного пептида 1, инсулина и лептина. Относительный шанс наличия ХС-ЛНП ≥4,2 ммоль/л ассоциирован с повышением уровня С-пептида (отношение шансов 2,042, 95% доверительный интервал 1,209–3,449, p = 0,008) и уменьшением уровня глюкагоноподобного пептида 1 (отношение шансов 0,997, 95% доверительный интервал 0,996–0,999, p = 0,001).Заключение. Повышение уровня ХС-ЛНП у молодых людей ассоциировано с нарушениями не только липидного, но и углеводного обмена. Эти данные подтверждает изменение в крови метаболических маркеров, характеризующих нарушение обменных процессов в организме человека