Researches and grounds of design of pharmaceutical development and industrial introduction of production of parenteral preparations on the basis of recombinant proteins

In the conditions of introduction of the proper practice of production of medicinal facilities on pharmaceutical enterprises in Ukraine, it is necessary to develop effective measures of projects management for creation of favourable conditions for modernisation of pharmaceutical production, innovative management and management of development projects. The optimization of pharmaceutical production of injection preparations, modernisation of the pharmaceutical industries, is being implemented in accordance with the standards of GM

Acute Kidney Injury after Transcatheter Aortic Valve Implantation

Aim. The aim of the study was to evaluate the incidence and predictors of acute kidney injury (AKI) associated with transcatheter aortic valve implantation (TAVI).Material and methods. 50 patients (39 women, 11 men) aged 76 (71; 80) years who underwent TAVI were examined. One day after TAVI, blood creatinine level was determined by the Jaffe method and troponin I by a highly sensitive method (hs-cTnI). Acute kidney injury (AKI) was diagnosed according to the KDIGO criteria (2012). The following hospital complications were evaluated: cases of cardiac death, intraoperative myocardial infarction (MI), stroke and transient ischemic attack, permanent pacemaker implantation, recurrent paroxysms of atrial fibrillation.Results. History of MI had 22% of patients, percutaneous coronary intervention – 38%, hypertension – 98%, chronic kidney disease – 48%, diabetes mellitus – 24%, class II NYHA of chronic heart failure (CHF) – 52%, NYHA class III – 46%, NYHA class IV – 2%. The risk of operational mortality according to EuroSCORE II was 6.3±5.4%. AKI after TAVI was registered in 6 (12%) patients (1 grade AKI – 8%, 2 grade – 2%, 3 grade – 2%). Parameters associated with AKI after TAVI were higher CHF NYHA class (p=0,020), high hs-cTnI level (p=0,013), intraoperative MI (p=0.035). The predictor of AKI after TAVI was high hs-cTnI level (odds ratio 4.0, 95% confidence interval 1.0-16.1). Among patients with AKI after TAVI in compare with patients without AKI, the cumulative frequency of cardiac death, MI, strokes and transient ischemic attacks, implantation of a permanent pacemaker, the proportion of people with paroxysmal atrial fibrillation during the hospital stay was 5,8 times higher (66.7% vs 11.4% respectively, p=0.001).Conclusion. AKI after TAVI was present in 12% of patients. The predictor for AKI development was an increase in hs-cTnI level after TAVI implantation. The hospital prognosis after TAVI is worse in patients with postoperative AKI

USE OF FIXED COMBINATIONS OF RAMIPRIL AND HYDROCHLOROTHIAZIDE IN PATIENTS WITH ARTERIAL HYPERTENSION AND HIGH OR VERY HIGH CARDIOVASCULAR RISK (OPTIMIST 2 STUDY): RESULTS OF THE NONCOMPARATIVE STUDY

Aim. To evaluate efficacy and safety of treatment with fixed combination of ramipril and hydrochlorothiazide in patients with arterial hypertension (HT) 2-3 degree and high or very high cardiovascular risk in clinical practice. Material and methods. Patients with HT 2-3 degree and high or very high cardiovascular risk who had not reached target blood pressure (BP) levels with previous therapy (n=427) were included in open-label non-comparative multicenter phase IV study. Patients were treated with fixed combination of ramipril and hydrochlorothiazide during 8 weeks. The drug dose was increased and/or amlodipine was added in case of insufficient antihypertensive effect. Achievement of the target BP level (<130/80 mmHg) and therapy safety were assessed. Results. 420 patients (98.4%) completed the study. After 8 weeks 273 (65%) patients had a two-component therapy (fixed combination of ramipril and hydrochlorothiazide), 147 (35%) patients — triple therapy (ramipril, hydrochlorothiazide and amlodipine). The target BP level was achieved in 408 (97.14%) patients and it was not reached in 12 (2.86%) patients. 7 patients were dropped out from the study: 4 — because of adverse events (dry cough), 3 — due to violation of study protocol. Both patients and doctors considered fixed ramipril and hydrochlorothiazide combination as effective and well tolerable one.  Conclusion. Ramipril and hydrochlorothiazide fixed combination provides an achievement of the target BP level in the most of HT patients

Assessment of the psycho-emotional state of patients after COVID-19-associated pneumonia in relationship with laboratory indicators

The aim. To study peculiarities and association of psychological and laboratory indicators in patients with cardiovascular diseases (CVD) who underwent COVID-19 to clarify the factors affecting the possibility of developing delayed psychological and cardiovascular adverse events.Methods. The study enrolled 350 patients with COVID-19. Group 1 consisted of 92 patients without CVD, Group 2 – of 258 patients with CVD. Indicators of laboratory and psychological parameters were assessed according to the data of psychological questionnaire using GAD-7 (General Anxiety Disorder-7), PHQ-9 (Patient Health Questionnaire-9), PSS (Perceived Stress Scale) screening scales and SF-36. Parameters of complete blood count and biochemical blood tests were measured during hospitalization and three months after discharge from the monohospital.Results. After three months, in the general group of patients, signs of anxiety and depression were detected in more than 30 % of the examined patients, signs of stress – in 10.4 %. In the group with CVD, psycho-emotional disorders were identified in 1/4 of the patients, and severe stress – in 8 % of those included in the study. In addition, it was registered that the indicators of erythrocyte sedimentation rate, fibrinogen, high-sensitivity C-reactive protein (CRP), homocysteine and IL-6 remained at a higher level in the second group.Correlation analysis showed that the psychological component of health is interconnected with the level of neutrophils (p = 0.044) and fibrinogen (p = 0.050); the physical component of health is correlated with the level of erythrocytes (p = 0.030), hemoglobin (p = 0.015), CRP (p = 0.002), creatine phosphokinase (p = 0.036) and glucose (p = 0.017). Regression analysis revealed that in patients with CVD three months after hospitalization, an increased glucose index contributes to deterioration, and increased hematocrit and mean hemoglobin concentration improve the quality of life of patients.Conclusion. Laboratory markers that maintain the duration of a prolonged vascular reaction, violation of the rheological and metabolic properties of blood, determine the nature of the development of both psychological and cardiovascular complications

Clinical cases non-compact myocardium. Diagnostics, tactics

The article describes a clinical case of non-compact form of a non-isolated myocardium. The diagnosis is made in the performance of transthoracic echocardiography. Echocardiography has sufficiently high information in the recognition of a non-compact myocardium of the left ventricle and for the differential diagnosis with other cardiomyopathies, so you can use it as a base the most accessible, acceptable method in the case of non-compact myocardium cardiomyopathy.В статье приводится описание клинических случаев неизолированной формы некомпактного миокарда. Диагноз поставлен при выполнении трансторакальной эхокардиографии. Эхокардиография обладает достаточно высокой информативностью в распознавании некомпактного миокарда левого желудочка и для проведения дифференциальной диагностики с другими кардиомиопатиями, что позволяет использовать ее в качестве основного наиболее доступного и приемлемого метода в случае кардиомиопатии некомпактного миокарда

ГЕНДЕРНЫЕ ОСОБЕННОСТИ И ТАКТИКА ЛЕЧЕНИЯ ОСТРОГО КОРОНАРНОГО СИНДРОМА БЕЗ ПОДЪЕМА СЕГМЕНТА ST У ЖЕНЩИНЫ МОЛОДОГО ВОЗРАСТА

Acute coronary syndrome in young women is of particular interest for today’s research. There are some data on the different effects of major risk factors among the sex groups, driven by the presence of specific risk factors in the female population. The clinical case reports different clinical course of atherosclerosis in men and women, presented with non-stenotic coronary atherosclerosis with hormonal imbalance and classical risk factors of complicated CAD.Острый коронарный синдром у женщин молодого возраста становится актуальной проблемой. Известны данные о разнонаправленных влияниях основных факторов риска в зависимости от пола и с учетом реализации специфических факторов риска женской популяции. Приводится случай из практики, демонстрирующий иное клиническое течение атеросклероза коронарных артерий у мужчин и женщин: выявление нестенозирующей формы коронарного атеросклероза на фоне нарушения гормонального статуса и «классических» факторов риска осложненного течения ИБС

Biochemical parameters associated with endothelial dysfunction in patients with arterial hypertension and ischemic heart disease

With the purpose to study the characteristic of biochemical parameters related to endothelial dysfunction, a survey of 121 people aged between 40 and 70 years. The control group without arterial hypertension (AH) and coronary heart disease (CHD) accounted for 18 people, a group with AH - 56 people, the group with the combination of CHD and AH - 47. A comparative evaluation of vasomotor function of endothelium and endothelial dysfunction characterizing the biochemical parameters as endothelin-1, nitrites blood plasma, ADP-induced platelet aggregation, lipid peroxidation and antioxidant defense in blood platelets from patients with AH and with combined AH and CHD. In patients with AH and accession of CHD was identified by negative dynamics of markers of ED, in the form of reduced levels of nitrite, the increase of endothelin-1 and platelet aggregation (AT), induced by the large doses of inducer. The studied group was predominantly at one stage or another oxidative stress is caused by an imbalance of antioxidant protection (AOP) and the processes of lipid peroxidation (LPO) in platelets, in patients with AH was dominated by activation of the LPO. In patients with in combination AH with CHD had a complete depletion of the AOP and a decrease in the activity of LPO in platelets and significantly higher values AT.С целью изучения особенностей биохимических показателей, связанных с дисфункцией эндотелия, проведено обследование 121 человека в возрасте от 40 до 70 лет. Контрольную группу без артериальной гипертонии (АГ) и ишемической болезни сердца (ИБС) составили 18 человек, группу с АГ - 56 человек, группу с сочетанием АГ и ИБС - 47 человек. В работе проведена сравнительная оценка сосудодвигательной функции эндотелия и таких характеризующих эндотелиальную дисфункцию биохимических показателей как эндотелин-1, нитриты плазмы крови, АДФ-индуцированная агрегация тромбоцитов, перекисное окисление липидов и антиоксидантная защита в тромбоцитах у пациентов с АГ и сочетанием АГ и ИБС. У пациентов АГ по мере присоединения ИБС была выявлена отрицательная динамика маркеров ЭД, в виде снижение уровня нитритов, повышения эндотелина-1 и агрегации тромбоцитов (АТ), индуцированной большими дозами индуктора. Исследуемые группы находились преимущественно на той или иной стадии окислительного стресса, обусловленного дисбалансом антиоксидантной защиты (АОЗ) и процессов перекисного окисления липидов (ПОЛ) в тромбоцитах, у больных АГ преобладала активация ПОЛ. У больных АГ в сочетании с ИБС наблюдалось полное истощение АОЗ и снижение активности ПОЛ в тромбоцитах и более высокие значения АТ

Features of ambulatory blood pressure monitoring in patients with secondary renovascular hypertension

The aim of the study was to evaluate the characteristics ot the daily profile of blood pressure in patients with renovascular hypertension. We examined 16 patients with unilateral atherosclerotic renal artery stenosis compared with patients with refractory essential hypertension. The technique of ambulatory blood pressure monitoring was used. Standard parameters of monitoring were evaluated. We realized that the characteristics of circadian rhythm of blood pressure in patients with renovascular hypertension are to reduce the degree of nocturnal reduction of systolic and diastolic blood pressure (prevalence of abnormal circadian rhythms of ‘non-dipper1 and ‘night-picker”); increased variability of systolic blood pressure at night, the tendency to form high rate of morning rise in blood pressure.Целью исследования явилась оценка особенностей суточного профиля артериального давления у больных реноваскулярной гипертонией. Обследовано 16 пациентов с артериальной гипертонией на фоне одностороннего атеросклеротического стеноза почечной артерии в сравнении с пациентами с рефракторной эссенциальной артериальной гипертонией. Использовалась методика суточного мониторирования артериального давления на аппарате АВРМ- 02М, оценивались стандартные параметры суточного профиля. Выявлено, что особенностями суточного ритма артериального давления у пациентов с вазоренальной гипертонией являются уменьшение степени ночного снижения САД и ДАД (преобладание патологических циркадных ритмов «нон-диппер» и «найт-пикер»); повышение вариабельности систолического АД в ночные часы, тенденция к формированию высокой скорости утреннего подъема АД

Features parameters of the lipid profile and inflammatory vascular respons in patients with stable and unstable angina

169 patients (male and temale aged 60,12 ± 10,7 years) with coronary artery disease (CAD), stable and unstable angina (SA/UA) were examined. According to the selective coronary angiography, a group of patients with significant and insignificant (neighboring) coronary stenosis (SCS and ICS) was selected. CAD patients with SA and UA in the general group do not differ in the level of atherogenic parameters of lipid profile, but in UA group the level of MMP-9 and TIMP-1 is significantly higher, which may indicate an elevated level of the local inflammatory respond and increased threat of thrombogenic complications in unstable plaques. In CAD patients with UA in SCS group a significant excess of atherogenic parameters of lipid profile (total cholesterol, LDL cholesterol, trygliceride) compared to patients without SCS was noted. Equal elevation of inflammatory markers (hs-CRP, TNF-alpha and endothelin-1) in both groups regardless severity of coronary syndrome may cause thrombosis in case of unstable CAD. Patients with unstable CAD regardless of the severity of coronary stenosis may have increased level of MMP-9 and TIMP-1. According to logistic regression data, CD 40, MMP-9 and TIMP-1 levels can be isolated as differential signs of unstable angina flow.Обследовано 169 пациентов (мужского и женского пола) в возрасте 60,12±10,7 лет с ишемической болезнью сердца (ИБС), разделенных в 2 основные группы: 1-я пациенты со стабильной (СС) и 2-я пациенты с нестабильной стенокардией (НС). Согласно данным селективной коронарной ангиографии, в каждой основной группе пациентов выделены подгруппы со значимым и незначимым коронарным стенозом (ЗКС и НЗКС). Пациенты со СС и НС стенокардией в основных группах не различались по уровню атерогенных параметров липидного спектра и основных маркеров воспалительной сосудистой реакции, однако в группе с нестабильной стенокардией был зарегистрирован достоверно повышенный уровень ММП-9 и ТИМП-1, что свидетельствует о наличии повышенного уровня маркеров локального воспалительного ответа. У пациентов ИБС с нестабильной стенокардией в группах независимо от степени коронарного стеноза зарегистрировано превышение референсных знамений атерогенных параметров липидов (ОХС, ТГ, ХС ЛПНП) и равноценно повышенные уровни маркеров сосудистого воспаления вч-СРБ, ФИО- и эндотелина-1, что может обусловливать при нестабильном течении стенокардии равнозначную вероятность нежелательных сердечно-сосудистых событий. Согласно данным логистической регрессии, уровни CD 40, ММП-9 и ТИМП-1 можно использовать для верификации нестабильного течения стенокардии