Репозиторий Университета

© 2019, © 2019 Informa UK Limited, trading as Taylor  &  Francis Group. The recent developments in Cathepsin protease research have unveiled a number of key observations which are fundamental to further our understanding of normal cellular homeostasis and disease. By far, the most interesting and promising area of Cathepsin biology stems from how these proteins are linked to the fate of living cells through the phenomenon of Lysosomal Leakage and Lysosomal Membrane Permeabilisation. While extracellular Cathepsins are generally believed to be of central importance in tumour progression, through their ability to modulate the architecture of the Extracellular Matrix, intracellular Cathepsins have been established as being of extreme significance in mediating cell death through Apoptosis. With these two juxtaposed key research areas in mind, the focus of this review highlights recent advancements in how this fast-paced area of Cathepsin research has recently evolved in the context of their mechanistic regulation in cancer research. Abbreviations : ECM, Extracellular Matrix; MMP, Matrix Metalloproteases; LL, Lysosomal Leakage; LMP, Lysosomal Membrane Permeabilisation; LMA, Lysosomorphic Agents; BC, Breast Cancer; ASM, Acid Sphingomyelinase; TNF-α, Tumor Necrosis Factor-alpha; LAMP, Lysosomal Associated membrane Protein; PCD, Programmed Cell Death; PDAC, Pancreatic Ductal Adenocarcinoma; ROS, Reactive Oxygen Species; aa, amino acids.

© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. Aim. To evaluate a complex clinical efficacy, tolerability and safety of statin drugs - simvastatin, atorvastatin, rosuvastatin in patients with hyperlipidemia (HL). Material and methods. The assessment of clinical efficacy was done in 90 patients with HL and arterial hypertension of the grades 1 and 2, age 40-75 y.o.; some of them had coronary heart disease. Results. In 90 patients with cardiac pathology and HL, selected to 3 groups by 30 persons, the clinical efficacy of the listed statins was assessed. A significant hypolipidemic effect was noted as a decline of atherogenicity of the blood, with slight more prominent effect of rosuvastatin. Conclusion. The data makes it to conclude the simvastatin, atorvastatin and rosuvastatin are equally effective hypolipidemic drugs in HL type IIA and IIB patients. The time frame, type and grade of positive changes in lipid profile are almost the same, and in rosuvastatin just slightly more prominent.

© 2018 Stolichnaya Izdatelskaya Kompaniya. Cardiovascular diseases occupy a leading position in morbidity, mortality and disability in most countries. Ischemic heart disease and stroke lead in the structure of mortality from cardiovascular diseases. The issues of lipid-lowering therapy with statins in the aspect of stroke prevention are discussed in the article. The main risk factors of atherosclerosis and their prevalence are presented. Topical standards for statin use, evidence-based medicine data obtained in randomized clinical trials, and evidence from actual clinical practice are covered. Possible promising areas of statin use for the prevention of acute cerebrovascular accident are also considered. Combination therapy together with other lipid-lowering drugs, as well as drugs of other pharmacological groups, the use of statins from earlier ages, the practical implementation of pleiotropic effects of statins can be attributed to the latter. The authors clearly demonstrate that the actual practice of using statins lags significantly behind the ideal, reflected in the recommendations and randomized clinical trials. Adherence to medical recommendations is one of the key factors in this. The main factors that can influence the increase of adherence of patients to taking statins and increase the effectiveness of their application in real clinical practice are presented..

© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: Assessing the dynamics of vulnerability of atherosclerotic plaques in patients with angina pectoris on atorvastatin therapy (40 mg for 10-12 months) based on coronary computed tomography angiography (CCTA) data. Materials and methods: The study prospectively enrolled 74 patients with angina pectoris not medicated with statins. All patients underwent CCTA. 30 patients with vulnerability of atherosclerotic plaques were selected for further observation and atorvastatin was administered to them at dose of 40 mg. Repeated tomography scans were recorded 10-12 months later. Images were analyzed by "Vitrea" workstation in a blind manner. Statistical processing was performed on SPSS version 11.5 software (BioStat). Results: Statistically insignificant decrease in: total plaque volume (from 188.64 ± 35.8 to 184.96 ± 34.45 mm3), low-attenuation plaque (from 60.46 ± 12.87 to 57.06 ± 12.34 mm3), degree of stenosis (from 41.6 ± 3.16 to 40.65 ± 3.26%), spotty calcification (from 86.0 to 90%), remodeling index (from 1.25 [1,0;1,4] to 1.1 [1,0;1,4]), napkin-ring sign (from 69.76 to 60%), irregularity of the contour (from 79.1 to 65%). LDL levels decreased from 3.23 ± 0.33 to 2.76 ± 0.27 mmol/L. Statistically significant decrease of total cholesterol was from 5.75 ± 0.45 to 4.42 ± 0.57 mmol/L. The study also revealed statistically significant positive correlation between decrease of LDL levels and total plaque volume decrease (R=0.51, P=0.002), mainly because of lowattenuation components. Conclusion: We review our experience of using CCTA for noninvasive monitoring of vulnerability of atherosclerotic plaques in dynamics and show that atherosclerotic plaques stabilize on long-term atorvastatin treatment.

© 2018 Stolichnaya Izdatelskaya Kompaniya. Статины в настоящее время являются наиболее широко применяемыми препаратами для лечения дислипидемии и наиболее эффективными лекарствами для снижения уровня холестерина липопротеинов низкой плотности и снижения риска сердечно-сосудистых и цереброваску- лярных событий. Считается, как правило, что статины хорошо переносятся, но предполагают потенциальную связь между статинами и ког- нитивными нарушениями у некоторых людей. Эта обзорная работа была проведена с учетом поиска информации о конкретной проблеме потенциального неблагоприятного влияния статинов на когнитивную сферу, целью которой было выявить рекомендации для медицинских работников по мониторингу и снижению риска потенциальных когнитивных нарушений при терапии статинами. Розувастатин, по-видимому, является более безопасным среди статинов с точки зрения влияния на когнитивную функцию. Перед началом терапии статинами нет не- обходимости в выявлении когнитивной дисфункции у пациентов, терапия статинами не сопровождается риском развития когнитивной дисфункции по данным когортных и рандомизированных исследований. При развитии когнитивной дисфункции на фоне терапии статинами необходимо доказать ее наличие и исключить другие возможные факторы ее возникновения, и оценить соотношение пользы/риска отмены терапии статинами. На основании индивидуальных особенностей пациента возможно уменьшить дозу принимаемого статина или прекратить прием препарата для оценки обратимости симптомов. В случае прекращения приема статина следует подумать об альтернативной замене на другой ингибитор ГМК-КоАредуктазы, предпочтительнее - препарат, меньше всего проникающий через гематоэнцефалический барьер, такой как розувастатин.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. Steady increase in the prevalence of chronic kidney disease (CKD) is a serious public health problem, since CKD potentially leads to the development of end-stage renal disease (ESRD) that requires high-cost replacement therapy and is closely associated with increased risk of developing cardiovascular diseases (CVD), which are the cause of death in most patients. Progression of renal dysfunction and development of CVD are significantly affected by hyper- and dyslipidemia. This review contains results of studies evaluating the effect of hypolipidemic therapy on reduction of cardiovascular risk and slowdown of renal dysfunction in patients with CKD at pre-dialysis and dialysis stages of renal failure, as well as in patients with kidney transplant. In addition, recommendations on nutrition and new therapeutic approaches to lipid-lowering therapy in patients with CKD, as well as prospects for the usage of new hypolipidemic drugs are also presented.

© 2017, Springer Science+Business Media, LLC. Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.

Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.

Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.