Associations of Arterial Stiffness and Bone Mineral Density in Postmenopausal Women

Aim. To study associations  between arterial stiffness and bone mineral density in postmenopausal women.Material and methods. The intima-media thickness  (IMT), the presence  and  number  of atherosclerotic  plaques  (AP) were studied  using  duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation. The Bone mineral density (BMD) of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry.Results. A significant  correlation  of PWV  with  age,  duration  of menopause was  revealed,  a more pronounced correlation  was  noted  with  blood pressure (BP), maximum IMT thickness.  There was no significant  correlation  between  PWV  and BMD.  AI showed  a statistically  significant but weak negative  correlation  with  the HN  (rs=0.12, p<0.05); a more  pronounced negative  correlation  was  obtained  for BMD  (rs=0.16, p<0.01). For indicators characterizing the degree of bone mass increased,  there is a significant  correlation with age (rs=-0.4, p<0.01), weight (rs=0.4, p<0.01), Quetelet index (rs=0.3, p<0.01) and the presence of AP (rs=-0.12, p<0.05). According to the results of multivariate regression  analysis,  the most significant  predictors of arterial stiffness were indicators  reflecting  obesity and diastolic BP. The relationship  between BMD and age-adjusted vascular stiffness was not statistically significant.Conclusion. In our study, postmenopausal women have increased arterial stiffness,  suggesting a higher risk of cardiovascular disease. The relationship between  bone mineral density and vascular  wall stiffness  was insignificant. To a greater extent,  arterial stiffness  depended  on age,  increased  blood pressure, and the presence of atherosclerotic  changes

Association of Heart Rate Variability with the Psychosocial Stress Level in Men 41-44 Years Old Living in Moscow

Aim. Research of the association of heart rate variability (HRV) with the level of psychosocial stress (PS) and other indicators of the risk of cardiovascular diseases in a sample of 41-44-year-old men living in Moscow.Material and methods. A total of 299 men aged 41-44 years were examined. The study included a clinical examination and a survey using a standard questionnaire. The categorization of risk factors (RF) for cardiovascular diseases (CVD) was carried out in accordance with generally accepted criteria The psychosocial stress was assessed using the Reeder scale. Depending on the psychosocial stress level, all surveyed men were divided into 3 groups by terciles: group 1 (3,28-4,0 points) – mild stress, group 2 (2,71-3,14) – moderate stress, group 3 (1,28-2,57) – severe stress. The analysis of HRV was performed on the basis of a short recording of an electrocardiogram using the original software package.Results. Nonparametric ANOVA showed that the mean [M (95% CI)] values of the HRV time domain (SDNN, rMSSD and the state of regulatory reserves) were lower in the group of men with high PS compared with the group with low PS [25.3 ms (20.9-29.7) versus 40.5 ms (30.7-50.3), p=0.007; 29.5 ms (24.6-34.3) versus 49.5 ms (36.7-62.3), p=0.030; and 46.7 (44.7-48.6) versus 49.7 (48.1-51.4), p=0.019; respectively]. On the contrary, the mean values [M (95% CI)] of the integral indicators of HRV (SI and IVR) were higher in the group of men with high PS [635.8 c.u. (556.2-715.4) versus 488.9 (423.8-554.1), p=0.005; 1172.6 (1045.1-1300.1) versus 904.7 (790.0-1019.4), p=0.003; respectively]. The results of correlation and multiple regression analysis confirmed that these HRV indicators are statistically significantly associated not only with PS, but also with other indicators (age, waist / hip ratio, diastolic blood pressure). However, their predictive value turned out to be low, and the proportion of the explained variance of HRV indices ranged from 2.5 to 13.1%.Conclusion. The weakening of the autonomous regulation of the heart rate with a decrease in the activity of the parasympathetic link, the activation of the central circuit of regulation with the prevalence of sympathetic influences, a decrease in the functional reserves of the heart rate regulation system are associated with an increase in the level of PS and other indicators of the risk of cardiovascular diseases

Ultrasound examination with contrast in the diagnosis of inflammatory bowel disease. The results of the pilot study

Aim. Assessment of diagnostic significance of informativeness and security of ultrasonography with contrast enhancement drug SonoVue in the diagnosis of Crohn's disease (CD) and ulcerative colitis (UC). Materials and methods. The pilot conducted a prospective study which involved 15 patients with inflammatory bowel disease (IBD). All patients gave written consent to participate in the study and processing of personal data. The study included adult patients with an established diagnosis of UC and CD, with proven clinical activity of the disease. Activity was evaluated based on clinical and laboratory data on the scale of best (CDAI >150) for patients with CD and on a scale of Trulove-Witts (2-3 stage) and the Mayo index (DAI) for patients with UC. All the patients underwent colonoscopy with biopsy, ultrasound examination of abdominal cavity organs with the study of the vascularization of the intestinal wall (color Doppler, power Doppler, contrast study). Results. The use of contrast showed additional features in the instrumental evaluation of activity of inflammatory process, identification of complications and assessment of prognosis. Conclusion. The results of ultrasound of the bowel with contrast can be used to assess the activity and stage of disease in patients with UC or CD

Клеточная терапия аутологичными мезенхимальными стромальными клетками у пациентов с лекарственно-устойчивым туберкулезом легких

The objective: to evaluate the effectiveness of treatment with autologous mesenchymal stromal cells (MSCs) in patients with drug resistant pulmonary tuberculosis (DR TB).Subjects and Methods. 120 patients with drug resistant tuberculosis aged 18 to 61 years old were enrolled in the study. They all were treated at the Republican Scientific and Practical Center of Pulmonology and Phthisiology from 2009 to 2018. Against the background of anti-tuberculosis treatment, patients (60 people) from Main Group (MG) underwent bone marrow sampling and then intravenous administration of autologous MSCs.Results. The average dose of administered cells was 1x106 per kg of the patient body weight. The average duration of MSC cultivation made 35 days. Treatment effectiveness in MG made 90% versus 71% in Control Group (CG). All patients who were successfully cured of tuberculosis (TB) using autologous MSCs had no tuberculosis relapses during 5 years of follow-up. In Control Group, 8 (19%) cases of relapse were reported. In Main Group versus Comparison Group, the rates indicating healing of cavities and absence of relapse are statistically significantly better.Conclusion. The use of autologous MSCs in patients with drug resistant tuberculosis has shown its high effectiveness.Цель исследования: оценка эффективности применения аутологичных мезенхимальных стромальных клеток (МСК) у пациентов с лекарственно-устойчивым туберкулезом (ЛУ-ТБ) легких.Материалы и методы. В исследование было включено 120 пациентов в возрасте от 18 до 61 года с ЛУ-ТБ, находившихся на лечении в государственном учреждении «Республиканский научно-практический центр пульмонологии и фтизиатрии» с 2009 по 2018 гг. На фоне противотуберкулезного лечения пациентам (60 чел.) основной группы (ОГ) проводился забор костного мозга, а затем внутривенное введение аутологичных МСК.Результаты. Средняя доза вводимых клеток составила 1х106 на кг массы тела пациента. Средняя длительность культивации МСК была 35 дней. Эффективность лечения в ОГ составила 90% в сравнении с 71% в контрольной группе (КГ). У всех пациентов, успешно излечившихся от туберкулеза (ТБ) с применением аутологичных МСК, рецидивов ТБ в течение 5 лет наблюдения не было. В контрольной группе было зарегистрировано 8 (19%) случаев рецидива. В ОГ по сравнению с КГ показатели по закрытию полостей распада и отсутствию рецидива статистически значимо лучше.Заключение. Применение аутологичных МСК у пациентов с ЛУ-ТБ показало высокую эффективность

Association of smoking with indicators of the structure and function of left ventricle of the heart in middle-aged men

Aim. Evaluation of the association of smoking (status, intensity and duration) with indicators of the structure and function of the left ventricle of the heart in a sample of middle-aged men.Material and methods. This study is part of a 32-year prospective cohort observation of men from childhood (11-12 years). 301 (30.0%) representatives of the original population sample aged 41-44 years were included in the study. The examination included a survey on intensity of smoking, anthropometry, measuring blood pressure, pulse rate, echocardiography, and blood lipid analysis.Results. 301 men aged 41-44 included 92 (30.6%) men who had never smoked, 73 (24.3%) men smoked in the past and 136 (45.2%) men currently smoke. 75% of current smokers started smoking before age 19, of which 32.3% started smoking before age 15. The duration of smoking cessation among former smokers was 14.4 (12.5; 16.2) years. The average duration of smoking [average (95% confidence interval)] among former smokers was 14.4 (12.5; 16.2), for current smokers – 25.3 (24.6; 26.0) years. Current smoking was statistically significantly associated with higher mean values of the left ventricular myocardium mass (LVMM), the left ventricular myocardial mass index (LVMMI), the end-systolic and end-diastolic interventricular septum thickness (IVSTs/IVSTd), the end-systolic left ventricular posterior wall thickness (LVPWs), and the intensity and duration of current smoking were associated with higher values of the relative wall thickness of the left ventricle, the end-diastolic interventricular septum thickness, the end-systolic interventricular septum thickness, and with low values of the left ventricular stroke volume index (LV SVI). Multiple regression analysis showed that current smoking has an independent effect on the left ventricular myocardium mass, the left ventricular myocardial mass index and the end-diastolic interventricular septum thickness, and the duration and intensity of smoking has an effect on the index of the left ventricular stroke volume index.Conclusion. Current smoking, duration and intensity in middle-aged men is associated with unfavorable changes in indicators of the structure and function of the left ventricle of the heart. Efforts for primary prevention of smoking should begin as early as childhood and continue into adolescence and young adulthood

DETERMINATION OF POLYSORBATES BY SPECTROPHOTOMETRY IN DRUGS BASED ON RECOMBINANT PROTEINS

Method of determination of polysorbate 20 and polysorbate 80 in recombinant protein drugs based on spectrophotometry has been designed. Isolation of polysorbate from solution is carried out by solid phase extraction followed by elution of polysorbate with acetonitrile. Acetonitrile solution is evaporated and then polysorbate is derivatized with ferrous-thiocyanate reagent. Obtained derivative is extracted into organic phase and optical density is measured. The most optimal conditions of derivatization, extraction into organic phase and measurment was chosen. The validation was performed: specificity, linearity, accuracy, precision, robustness, limit of quantification

QUANTITATIVE DETERMINATION OF HOST CELL PROTEINS (CHO) BY THE METHOD OF ENZYME IMMUNOASSAY IN THE PROTEIN ADALIMUMAB

Is necessary to ensure thorough purification of the target proteins, since the presence of host cell proteins (HCP) from CHO cells in the final product is fraught with a number of negative consequences. Thus, it is has to reduce the contamination of HCP to minimum levels. A comparison of the immunoenzymatic assays of the second and third generations of Cygnus technologies for the quantification of host cell proteins (CHO) in a monoclonal antibody adalimumab was done. It was found that a kit of the 2nd generation does not show the true level of the host cell proteins, underestimating the result. In this connection, it becomes necessary to confirm the validity of the method for determining the total quantity of host cell proteins (CHO) by a set of 3rd generation in adalimumab substance according to the following analytical characteristics: system suitability test, specificity, limit of detection, limit of quantitation, hook capacity, precision

Association of Family History of Cardiovascular Diseases in Boys Aged 12-13 Years with Structural and Functional Indicators of the Left Ventricle and Arterial Stiffness in the Age of 43-46 Years (Results of 32-Year Prospective Follow-up)

Aim. To evaluate the association of Family History (FH) of cardiovascular diseases (CVD) in boys aged 12-13 years with the development of structural and functional changes in the left ventricle and stiffness of the main arteries in adulthood (43-46 years old) according to prospective study.Material and methods. For the initial examination, boys were selected whose parents suffered from CVD at a young age or died prematurely from them (risk group). The comparison group was formed from a population sample of boys of a similar age without FH of CVD. The examination included a survey on a standard questionnaire, measurement of anthropometric indicators, blood pressure (BP), pulse counting, determination of the blood lipid spectrum. The intima-media complex thickness (IMT) of the common carotid arteries was measured; echocardiography and applanation tonometry were performed.Results. The group with FH of CVD significantly (p<0.05) differed in childhood in terms of the body mass index (BMI) (18.8 vs 17.6 kg/m2), systolic BP (SBP) (117 vs 107 mm Hg), diastolic BP (DBP) (67 vs 56 mm Hg), average BP (81.8 vs 72.7 mm Hg) and triglycerides (0.79 vs 0.58 mmol/L). In adulthood, increased total cholesterol (TC) level (6.3 vs 5.8 mmol/L; p=0.036) and other indicators of atherogenesis were revealed in the risk group. The risk of fatal outcomes from CVD in the next 10 years in men with a family history of CVD in childhood was significantly higher compared to the control group (1.94 vs. 1.28; p <0.001). The main contribution to the total risk of fatal CVD in middle-aged men was made by TC and smoking. In the group with FH of CVD, higher stiffness of the arteries in adulthood was observed. There were found significant (p=0.002) intergroup differences in the IMT (0.73 vs 0.63 mm). A statistically significant positive relationship between BMI and some structural and functional indicators of the left ventricle and stiffness indicators of the main arteries was revealed. DBP and mean BP in childhood are associated with arterial stiffness in adulthood according to the parameters of central SBP and central DBP. BMI in boys is the most significant predictor for most structural and functional indicators of LV myocardial hypertrophy, in particular, LV myocardial mass (private R2=0.140) and interventricular septum thickness (R2=0.164; p=0.001), and arterial stiffness by central DBP parameter (R2=0.043; p=0.024) in adulthood. The risk of increased IMT development in males in adulthood with FH of CVD is 6.1 times higher than that of their peers without FH.Conclusion. FH of CVD revealed in childhood in males is a risk factor for the development of early atherosclerosis and, due to its ease of detection, can be used as one of the criteria for the formation of high-risk groups for the purpose of primary prevention

OSTEOPOROZ I SOSTOYaNIE SOSUDISTOY STENKI V ZAVISIMOSTI OT BIOMARKEROV KLETOChNOGO STARENIYa U ZhENShchIN V POSTMENOPAUZE

Цель: изучить взаимосвязь параметров сосудистой жесткости, МПК и биомаркеров клеточного старения у женщин в постменопаузальном периоде. Материал и методы. В одномоментное исследование включено 107 пациенток от 45 до 82 лет (ср. возраст -58 ± 0,86 лет), наблюдавшихся амбулаторно и подписавших информированное согласие. В исследование не включались пациентки с любыми клиническими проявлениями атеросклероза, злокачественными заболеваниями, с заболеваниями вызывающие вторичный остеопороз, принимающие препараты, влияющие на костный обмен и на показатели сосудистой жесткости. Толщина комплекса интима-медиа (ТКИМ), наличие и количество атеросклеротических бляшек (АБ), степень стеноза сонных артерий исследовались с помощью дуплексного сканирования. Оценка скорости распространения пульсовой волны (СРПВ), индекса аугментации (ИА) проводилось методом аппланационной тонометрии (SphygmoCor). СРПВ 10 м/с и более считали патологической. ИА считался нормальным при отрицательном его значении, положительный ИА свидетельствовал о повышенной жесткости. Был выбран медианный порог ИА- >20%. Значения более 0,9 мм принимались за повышение толщины КИМ. Толщина КИМ более 1,5 мм или локальное утолщение на 0,5 мм по сравнению со значениями КИМ в прилежащих участках сонной артерии свидетельствовали о наличии АБ. Для определения длины теломер (ДТ) в лейкоцитах использовался метод ПЦР в реальном времени. При этом проводилось измерение относительной длины теломер на геномной ДНК. Теломеры с диной >10,0 у.е. принимались за «длинные», а с длиной 10 м/с), более чем в 4 раза при ИА > 20%, толщины КИМ >0,9мм, в 2,45 раза при наличии АБ в сонных артериях и при наличии «коротких» теломер. Показатель АТ не ассоциировался с костной массой. С увеличением продолжительности менопаузы отмечалось постепенное увеличение показателей жесткости (СРПВ, ИА), толщины КИМ и снижение МПК во всех измеренных отделах скелета. Максимальные показатели сосудистой жесткости, наиболее низкая МПК и «самые короткие» теломеры были выявлены после 10 лет менопаузы. В многомерном регрессионном анализе отрицательная связь между ИА, толщиной КИМ и МПК осталась высокодостоверной, в то время как в отношении СРПВ, наличия АБ и ДТ эта ассоциация не подтвердилась. Заключение. Снижение МПК у женщин в постменопаузе ассоциируется с высокими показателями ИА и толщины КИМ. Короткие теломеры в 2,45 раза чаще встречались у пациентов с низкой костной массой, но связь не была подтверждена в регрессионном анализе, что исключает независимый характер связи этого маркера с МПК и свидетельствует в пользу того, что остеопороз является возраст-ассоциированным заболеванием, а не процессом естественного старения

Chronopharmacology of verapamil in Stage I-II arterial hypertension

Aim. To compare the pharmacokinetics and pharmacodynamics of verapamil retard, regularly taken by patients  with Stage I-II arterial hypertension (AH). Material and methods. The effects of the administration time (morning vs. evening) on verapamil retard pharmacokinetics were investigated. This open, randomised, cross-over study included 14 patients with Stage I-II AH,  who were regularly administered verapamil retard for 3 weeks. Before the active therapy started, all antihypertensive medications were withdrawn, with an exception of short-acting agents (“wash-out” period). Two weeks later,  the patients were administered verapamil retard, according to the randomisation scheme, and were recommended  to take one tablet in the morning or evening, at the same time every day. The first administration was at the clinic,  under medical supervision. Three weeks later, the participants were hospitalised for pharmacokinetics assessment. Seven days after the end of the first treatment course, a second course started, with an inverted time of verapamil retard administration. Blood concentration of non-modified verapamil was measured by high-performance liquid chromatography with fluorescent detection.Results. Significant differences in pharmacokinetics were observed for morning vs. evening verapamil administration. The respective maximal verapamil concentrations were 239,7±152,3 vs. 148,6±107,4 ng/ml (p<0,01), and respective half-life times were 12,50±3,48 vs. 22,57±15,24 hours (p<0,05). For other parameters, the difference was non-significant.Conclusion. In Stage I-II AH patients, the morning administration of Isoptin SR resulted in accelerated increase of its plasma concentration. At the same time, the evening administration was associated with increased half-life time and higher “concentration-effect” correlation, which makes the latter variant more rational