Effect of combined lipid-lowering therapy on atherosclerotic plaque vulnerability in patients with acute coronary syndrome (Combi-LLT ACS): randomized trial protocol

Aim. To study the effect of high-dose combined lipid-lowering therapy (statins + ezetimibe vs statins + PCSK9 inhibitors) on plaque vulnerability assessed using multimodal imaging (coronary computed tomography angiography (CCTA) and optical coherence tomography, as well as biomarkers in patients with acute coronary syndrome (ACS).Material and methods. This open, prospective, randomized, single-center study will include 120 patients admitted urgently with an ACS. All patients will undergo percutaneous coronary intervention of the infarct-related artery, as well as intracoronary imaging using optical coherence tomography of one or two noninfarct-related arteries. During hospitalization, patients will receive standard therapy for ACS according to clinical guidelines, while statins will initially be prescribed at a maximum dosage of atorvastatin 80 mg/rosuvastatin 40 mg.Patients who showed high compliance and did not reach the target low-density lipoprotein cholesterol (LDL-C) values (≤1,4 mmol/l) 1 month after myocardial infarction/unstable angina at the second visit will be randomized into two groups. Patients of group 1 will receive PCSK9 inhibitors (alirocumab 150 mg by subcutaneous injection once every 2 weeks or evolocumab 140 mg by subcutaneous injection once every 2 weeks) in addition to maximum statin therapy (atorvastatin 80 mg/rosuvastatin 40 mg), while group 2 participants will take ezetimibe at a dose of 10 mg in combination with the maximum dose of statins. In addition, at the second visit, patients will undergo CCTA, assess the cardio-ankle vascular index (CAVI) index and laboratory tests (complete blood count (neutrophil-to-lymphocyte ratio NLR), lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Troponin I, Galectin-3, high-sensitivity C-reactive protein (hs-CRP), metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL). Total follow-up will last 52 weeks. At the final visit, patients will undergo CCTA, assessment of the CAVI index and laboratory status (NLR, lipid profile, ALT, AST), Troponin I, Galectin-3, hs-CRP, MMP-9, TIMP-1, NGAL).Primary endpoint: reduction in plaque vulnerability according CCTA in non-infarct-related coronary arteries Secondary endpoints: death, stent thrombosis/restenosis, non-fatal myocardial infarction, readmissions with progressive angina, repeat revascularization; changes of the lipid profile (total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides) against the background of maximum combination therapy with statin + PCSK9 inhibitors or statin + ezetimibe; changes of the biomarkers of cardiac injury (Troponin I), inflammation (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).Conclusion. Our study will allow for the first time to compare and evaluate the effect of both PCSK9 inhibitors and ezetimibe in combination with high-dose statin therapy on reducing the plaque vulnerability according to CCTA in non-infarction-related coronary arteries in patients with ACS undergoing percutaneous coronary intervention, as well as to evaluate the diagnostic value of inflammatory biomarkers (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1)

Nanоbiocomposite based on dihydroquercetin and arabinogalactan in the form of a gel for external use as a means for the treatment of chronic venous insufficiency in an experiment

Background. Due to the high prevalence of chronic venous insufficiency among the population, with a decrease in the quality of life of patients and their early disability, there is a need to develop modern effective and safe means for the prevention and treatment of this pathology. We have developed the optimal composition and technology of a gel for external use based on a nanobiocomposite of dihydroquercetin and arabinogalactan, which has a venoprotective effect. The article presents data on the results of a preclinical study of the safety and specific activity of the gel.The aim. To study the specific activity (decongestant, antitranssudative action) and safety of a gel for external use based on nanobiocomposite of dihydroquercetin and arabinogalactan used for the treatment of chronic venous insufficiency in the framework of preclinical studies.Materials and methods. The object of the study was a gel for external use based on dihydroquercetin and arabinogalactan nanobiocomposite. The study was conducted on 32 white male rats of the same age, for 15 days. The study of the pharmacological activity of a gel based on a nanobiocomposite of dihydroquercetin and arabinogalactan, was carried out on a model of acute venous stagnation in the tail of a rat (edema of non-inflammatory genesis), the dynamics of tail volume growth in the experimental and control group of animals was evaluated. The irritant effect of the gel on the skin of animals was also determined, the permeability of the capillaries of the skin was determined.Results. When studying the pharmacological activity of the gel on a model of acute venous stagnation in the tail, it was shown that a soft dosage form for external use developed on the basis of nanobiocomposite of dihydroquercetin and arabinogalactan has decongestant and antitranssudative activity. The presence of a locally irritating effect in the gel under study has not been established in the framework of the experiment.Conclusion. In the course of preclinical study of the gel of the nanobiocomposite dihydroquercetin and arabinogalactan on laboratory animals, its antitranssudative activity and safety have been proven

Complex Structure of Lasiopodomys mandarinus vinogradovi Sex Chromosomes, Sex Determination, and Intraspecific Autosomal Polymorphism.

The mandarin vole, Lasiopodomys mandarinus, is one of the most intriguing species among mammals with non-XX/XY sex chromosome system. It combines polymorphism in diploid chromosome numbers, variation in the morphology of autosomes, heteromorphism of X chromosomes, and several sex chromosome systems the origin of which remains unexplained. Here we elucidate the sex determination system in Lasiopodomys mandarinus vinogradovi using extensive karyotyping, crossbreeding experiments, molecular cytogenetic methods, and single chromosome DNA sequencing. Among 205 karyotyped voles, one male and three female combinations of sex chromosomes were revealed. The chromosome segregation pattern and karyomorph-related reproductive performances suggested an aberrant sex determination with almost half of the females carrying neo-X/neo-Y combination. The comparative chromosome painting strongly supported this proposition and revealed the mandarin vole sex chromosome systems originated due to at least two de novo autosomal translocations onto the ancestral X chromosome. The polymorphism in autosome 2 was not related to sex chromosome variability and was proved to result from pericentric inversions. Sequencing of microdissection derived of sex chromosomes allowed the determination of the coordinates for syntenic regions but did not reveal any Y-specific sequences. Several possible sex determination mechanisms as well as interpopulation karyological differences are discussed

The history of the development of the method of rheography in the XX-XXI centuries

Article describes the main historical milestones in the development of the method of rheography from the moment of inception to the present day. The special place in article is a breakthrough research on various aspects of this method using the techniques of computer analysis of reogram. The article provides a summary of the biophysical basics of rheography and objectivity of its application for assessing physiological functions of the cardiovascular system, proved the value of rheography in the study of biomechanics of blood circulation. The article provides information on the methods of registration of rheogram, fixation of electrodes and data about the capabilities and prospects of application of the method of rheography to assess the function of endothelium and elastic properties of the arterial wall.Статья содержит основные исторические вехи развития метода реографии с момента возникновения до наших дней. Особое место в статье занимают прорывные исследования различных аспектов данного метода с применением техники компьютерного анализа реограмм. В статье приводится краткая информация о биофизических основах реографии и объективность ее применения для оценки физиологических функции сердечно-сосудистой системы, обосновано значение реографии в изучении биомеханики кровообращения. В статье содержится информация о методиках регистрации реограмм, способах фиксации электродов и данные о возможностях и перспективах применения метода реографии для оценки функции эндотелия и эластических свойств артериальной стенки

The regional system perfection of medical products providing and quality assurance in Zabaykalsky region as the example

In article the short review the problems of the quality medicines current from the market is presented. On the basis of the existing problems complex research the model of system of medical products providing and quality assurance has been developed, to minimize the risk of defective and forged medicines application in the medical and pharmaceutical organizations of the region

(-)-SCLAREOL CONVERSION IN RITTER'S REACTION CONDITIONS

The main products of sclareol (1) Ritter’s reaction in mild conditions are (8R,13R)-Labd-14(15)-en-8,13-diacetamide (2) (8R,13S)-Labd-14(15)-en-8,13-diacetamide (3) stereoisomeric on C13 atom and having unrearranged native diol skeleton. We present in the current communication the results of sclareol converting (1) into nitrogen-containing labdanes in the Ritter’s reaction conditions

Growth and filling regularities of filamentary channels in non-metallic inorganic coatings under anodic oxidation of valve metals. Mathematical modeling

Theoretical models are developed for growth and filling processes in filamentary channels of nanostructured non-metallic coatings produced by anodizing and microplasma oxidation. Graphical concentration distributions are obtained for channel-reacting anions, cations, and sparingly soluble reaction products depending on the time of electric current transmission and the length of the filamentary channel. Graphical distributions of the front moving velocity for the sparingly soluble compound are presented. The resulting model representation increases the understanding of the anodic process nature and can be used for a description and prediction of porous anodic film growth and filling. It is shown that the character of the filamentary channel growth and filling causes a variety of processes determining the textured metal – nonmetallic inorganic coating phase boundary formation