EFFICACY AND SAFETY OF BISOPROLOL IN YOUNG MEN WITH ARTERIAL HYPERTENSION AND OBESITY

Aim. To evaluate effect of bisoprolol on circadian blood pressure (BP) profile, autonomic cardiovascular regulation, lipid and carbohydrate metabolism in young patients with arterial hypertension (HT) and obesity. Materials and methods. 36 men aged 18 to 35 years with HT 1-2 degrees, obesity 1-2 degrees and signs of sympathetic over activity were examined. In addition to standard clinical examination assessment of heart rate variability (HRV) during orthostatic test with spectral analysis, ambulatory BP monitoring, evaluation of lipid profile, oral glucose tolerance test, determination of immunoreactive insulin, insulin resistance index and functional activity of beta-cells were performed. Anthropometric measurements included body mass index and waist circumference. Bisoprolol in the initial dose of 5 mg QD orally for 12 weeks was assigned to all patients. After 12 weeks of bisoprolol treatment repeated examination was performed. Results. Significant changes in HRV after 12 weeks of treatment with bisoprolol was found. Parasympathetic influence of autonomic nervous system increased during orthostatic test. Contribution of the slow and very slow waves, which reflect sympathetic and neurohumoral activity , reduced. Total spectral power was significantly increased. Initial tachycardia reduced. Target BP values were achieved after 12 weeks of treatment with bisoprolol 5 mg QD. Increase in a number of dippers and decrease in a number of nondippers in terms of both systolic and diastolic BP was observed. Heart rate and HRV was significantly decreased. No adverse events in terms of lipid or carbohydrate metabolism were found during treatment with bisoprolol. Conclusion. Bisoprolol 12 week treatment resulted in sympathetic activity decrease and parasympathetic activity increase, achievement of BP target levels, improvement of BP circadian profile. Bisoprolol therapy in dose of 5 mg/day demonstrated metabolic neutrality in patients with risk factors of cardiovascular diseases and type 2 diabetes

Эпигенетические и генетические нарушения функций генов BRCA1 / 2 у больных солитарным раком яичников и раком яичников при полинеоплазии

Background. Ovarian cancer is a complex and poorly studied disease that kills nearly 70–80 % of patients. Therefore, practitioners are interested in any opportunity of improving survival of these patients. From this point of view, investigation of genetic and epigenetic functions associated with this pathology is quite promising.Objective: to assess clinical and morphological characteristics of tumors in ovarian cancer patients, considering the presence of mutations and methylation in the BRCA1/2 gene.Materials and methods. This study included 180 ovarian cancer patients (FIGO stage I–IV) treated in the N. N. Blokhin Russian Cancer Research Center between 2008 and 2019. Study participants were divided into 3 groups according to their BRCA status and the number of primary tumors. We collected and analyzed venous blood, biopsy samples of ovarian cancer, archived histological sections, and paraffin-embedded tissue blocks. DNA isolated from venous blood was used to identify the following germline mutation by pyrosequencing: BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, and BRCA26174delT. DNA isolated from biopsy specimens and paraffin-embedded tissue specimens was used to analyze methylation in the promoter regions of the BRCA1 and BRCA2 genes by bisulfite sequencing (PyroMark Q24 DNA Sequencer; Qiagen, USA) with specific primers targeting promoter regions of the BRCA1 and BRCA2 genes.Results. Molecular testing demonstrated that the frequency of BRCA1 gene mutations was 21.1 % (38/148) in patients with solitary ovarian cancer and 40.6 % (13/32) in patients with multiple primary ovarian cancers. The frequency of methylation of the BRCA1 gene promoter was 2.2 % (18/148) in patients with solitary ovarian cancer and 3.1 % (1 case) in patients with multiple primary ovarian cancers. All BRCA1 methylated ovarian tumors were serous adenocarcinomas, including high grade tumors in 15 patients (78.9 %) and low-grade tumors in 4 patients (21.1 %).Conclusion. Hypermethylation of the BRCA1 gene promoter was observed only in individuals with sporadic serous ovarian cancer. No methylation was detected in patients with non-serous ovarian cancer, as well as in patients carrying BRCA1 gene mutations (both with solitary ovarian cancer and with primary multiple ovarian tumors).Введение. Рак яичников (РЯ) – сложное и малоизученное заболевание, уносящее жизни до 70–80 % пациенток. Поэтому практических врачей интересует любая перспектива улучшения выживаемости данной категории больных. С этих позиций изучение генетических и эпигенетических функций, связанных с возникновением этой патологии, нам кажется своевременным и перспективным.Цель исследования – изучить клинико-морфологические особенности опухолей у больных РЯ с учетом наличия мутаций и метилирования генов BRCA1/2.Материалы и методы. В исследование было включено 180 больных РЯ (FIGO I–IV стадии), получавших лечение в ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России с 2008 по 2019 г. В соответствии с BRCA-статусом и количеством первичных опухолей пациентки были поделены на 3 группы. Объектами исследований явились венозная кровь больных, клинические образцы РЯ (биопсийный материал), а также архивные образцы гистологических препаратов и парафиновые блоки. Образцы ДНК из цельной крови пациенток протестированы на наличие герминальных мутаций BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA2 6174delT методом пиросеквенирования. ДНК из биопсийного материала и архивных парафиновых срезов проанализированы на наличие метилирования в промоторах генов BRCA1 и BRCA2 методом бисульфитного пиросеквенирования на приборе PyroMark Q24 (Qiagen, США) с использованием специфических праймеров, амплифицирующих локусы, содержащие промоторные области генов BRCA1 и BRCA2.Результаты. Проведенное молекулярно-генетическое тестирование показало, что частота встречаемости мутаций гена BRCA1 у больных солитарным РЯ составила 21,1 % (38/148), а у больных РЯ при полинеоплазии – 40,6 % (13/32). Частота встречаемости метилирования промотора гена BRCA1 у больных солитарным РЯ составила 12,2 % (18/148), а в группе больных РЯ при полинеоплазии – 3,1 % (1 наблюдение). В 100 % случаев опухоль яичников при наличии метилирования была представлена серозной аденокарциномой: в 15 (78,9 %) наблюдениях – high grade и в 4 (21,1 %) – low grade.Выводы. Гиперметилирование промотора BRCA1 было выявлено только в группе больных спорадическим серозным РЯ. Метилирование не было обнаружено у больных несерозным РЯ, а также у больных РЯ – носительниц мутаций гена BRCA1 (как при солитарном РЯ, так и при первично-множественном процессе)

FOCUS ON MAGNESIUM BASED DRUGS

Magnesium deficiency in the organism is one of the most common human deficiency states. The prevalence of magnesium deficiency is about 15%, and suboptimal magnesium level is observed more than in 30% of people in the general population. Clinical signs of hypomagnesaemia are observed in 40% of patients in general care hospitals, in 70% of patients - in intensive care units, and magnesium deficiency occurs in 90% of patients with acute coronary syndrome. Magnesium metabolic disorders in the organism accelerate significantly development of complications of coronary heart disease, hypertension, type 2 diabetes, asthma and a number of neurological and psychiatric diseases. The value of this macro in the body is well studied, and its daily need is identified depending on age and sex. It is known that magnesium intake with the food does not cover an organism need. It is a rationale for preventive and therapeutic use of magnesium based drugs in various diseases. Organic salts of magnesium are recommended for these purposes. Magnesium metabolic disorders, approaches to pharmacotherapeutic correction of magnesium deficiency, advantages of magnesium salts of orotic acid are reviewed

EXPERIENCE IN THE USE OF BISOPROLOL IN THE TREATMENT OF OUTPATIENT HYPERTENSIVE PATIENTS AFTER STROKE

Aim. To study the dynamics of blood pressure (BP), heart rate (HR), the sympathetic-vagal balance in patients with arterial hypertension (HT) III stage after stroke during therapy based on bisoprolol 5-10 mg/day.Material and methods. Patients (n=12) with HT stage III with stroke history were examined. Age of the patients was 62±7.4 years old. Laboratory tests, BP monitoring, evaluation of the ratio of low frequency (LF) and high frequency (HF) components of HR variability and average daily HR determination were performed in all patients at baseline, after 14 and 34 days after therapy initiation. Bisoprolol was administered at dose of 5-10 mg/day.Results. BP decreased to the target level in all patients after 14 days of treatment and persisted through 34 days. Average daily HR and LF/HF ratio decreased, reaching the optimal values after 34 days. Significant dynamics in metabolic parameters and side effects were not found.Conclusion. Target BP levels, a significant decrease in HR and sympathetic activity, increase in parasympathetic activity of the autonomic regulation occurred since 14-th day of therapy based on bisoprolol (5-10 mg/day). The received effects allowed patients to continue rehabilitation therapy, accompanied with physical exertion.</p