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Experimental use of selected cholesterol-lowering drugs as potential candidates in modification of the pathophysiology of Alzheimer's disease
Cibičková, Ľubica ; Bureš, Jan (advisor) ; Hlúbik, Pavol (referee) ; Jabor, Antonín (referee)
Rationale: The current standard treatment of Alzheimer's disease (AD) is represented by acetylcholinesterase (AChE) inhibitors. In the pathogenesis of AD, cholesterol is directly involved. Its blood and brain levels positively correlate with amyloid β (Aβ) - a peptide characteristic for AD and capable of increasing AChE activity. Based on these data, we may suppose that cholesterol-lowering medication such as statins and alendronate might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present studies was to investigate possible influence of two lipophilic statins (simvastatin and atorvastatin) and alendronate on cholesterol synthesis in selected parts of the rat central nervous system (CNS) and other parameters relevant to Alzheimer's disease pathophysiology. Methods: We have performed 3 similar experiments on awaked rats that were administered simvastatin, atorvastatin, alendronate or aqua. At the conclusion of experiments, blood and brain parts were isolated and analyzed for cholesterol, lathosterol, hydroxymethylglutaryl- coenzyme A reductase protein, acetylcholinesterase activity, amyloid beta (40 and 42) and cholesterol synthesis rate. Results: All drugs at higher doses were able to lower cholesterol in the plasma, but none...
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Protein and amino acid metabolism in protein catabolic states - effect of leucine metabolites
Kovařík, Miroslav ; Holeček, Milan (advisor) ; Farghali, Hassan (referee) ; Hlúbik, Pavol (referee)
Protein catabolism and muscle wasting are basic features characterizing the complex metabolic syndrome, called cachexia, which is a severe complication of many diseases, in whose pathogenesis are often participant the systemic inflammatory response and endotoxemia. Branched-chain amino acids (leucine, isoleucine and valine) are not only an important substrate for protein synthesis, but they are also involved in the regulation of protein metabolism, insulin synthesis and secretion, and serve as the source of amino group in the alanine and glutamine formation in the muscle. Not only leucine but also some of its metabolites, - ketoisocaproic acid (KIC) and -hydroxy--methylbutyrate (HMB), have protein anabolic activity and thus some of leucine effects could be induced by these metabolites. In the last years there is paid attention to the HMB, which is used as a supplement for athletes and tested for its potential use in cachexia treatment. The aim of our experiments was to study: 1) endotoxin-induced effect on metabolism of proteins and amino acids in different types of skeletal muscle and the dose dependence of these changes; 2) effects of selected leucine metabolites (KIC and HMB) on the metabolism of proteins and amino acids - in different types of skeletal muscle; under in vivo and in vitro...
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Protein and amino acid metabolism in protein catabolic states - effect of leucine metabolites
Kovařík, Miroslav ; Holeček, Milan (advisor) ; Farghali, Hassan (referee) ; Hlúbik, Pavol (referee)
Protein catabolism and muscle wasting are basic features characterizing the complex metabolic syndrome, called cachexia, which is a severe complication of many diseases, in whose pathogenesis are often participant the systemic inflammatory response and endotoxemia. Branched-chain amino acids (leucine, isoleucine and valine) are not only an important substrate for protein synthesis, but they are also involved in the regulation of protein metabolism, insulin synthesis and secretion, and serve as the source of amino group in the alanine and glutamine formation in the muscle. Not only leucine but also some of its metabolites, - ketoisocaproic acid (KIC) and -hydroxy--methylbutyrate (HMB), have protein anabolic activity and thus some of leucine effects could be induced by these metabolites. In the last years there is paid attention to the HMB, which is used as a supplement for athletes and tested for its potential use in cachexia treatment. The aim of our experiments was to study: 1) endotoxin-induced effect on metabolism of proteins and amino acids in different types of skeletal muscle and the dose dependence of these changes; 2) effects of selected leucine metabolites (KIC and HMB) on the metabolism of proteins and amino acids - in different types of skeletal muscle; under in vivo and in vitro...
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Protein and amino acid metabolism in protein catabolic states - effect of leucine metabolites
Kovařík, Miroslav ; Holeček, Milan (advisor) ; Farghali, Hassan (referee) ; Hlúbik, Pavol (referee)
Protein catabolism and muscle wasting are basic features characterizing the complex metabolic syndrome, called cachexia, which is a severe complication of many diseases, in whose pathogenesis are often participant the systemic inflammatory response and endotoxemia. Branched-chain amino acids (leucine, isoleucine and valine) are not only an important substrate for protein synthesis, but they are also involved in the regulation of protein metabolism, insulin synthesis and secretion, and serve as the source of amino group in the alanine and glutamine formation in the muscle. Not only leucine but also some of its metabolites, - ketoisocaproic acid (KIC) and -hydroxy--methylbutyrate (HMB), have protein anabolic activity and thus some of leucine effects could be induced by these metabolites. In the last years there is paid attention to the HMB, which is used as a supplement for athletes and tested for its potential use in cachexia treatment. The aim of our experiments was to study: 1) endotoxin-induced effect on metabolism of proteins and amino acids in different types of skeletal muscle and the dose dependence of these changes; 2) effects of selected leucine metabolites (KIC and HMB) on the metabolism of proteins and amino acids - in different types of skeletal muscle; under in vivo and in vitro...
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Physical activity as a preventive component of the lifestyle of seniors
Vlastníková, Věra ; Fiala, Zdeněk (advisor) ; Hlúbik, Pavol (referee) ; Benešová, Veronika (referee)
This dissertation deals with physical activity of senior women and its importance in health prevention. Current knowledge in the areas of gerontology, exercise physiology and kinanthropology was summarized in the theoretical part. For experimental part of the work, questionnaires were compiled and group and individual exercise programs were created and applied on a set of senior women. The objective of the dissertation was to assess the influence of these programs on civilization diseases risk factors and on some indicators of quality of life. Our study population was formed by healthy senior women recruited from the programs of senior university education in Hradec Králové. The study population was further divided into an experimental group which completed a group exercise program (G1; 18 subjects, 63±3 yrs), an experimental group which completed an individual exercise program according to our instructions (G2; 14 subjects, 65±5 yrs) and a control group without an exercise program (G3; 19 subjects, 69±4 yrs). Exercise programs were applied for 10 months, 2 hours/week and contained remedial exercises, strengthening activities, balance and relaxation exercises and walking. The variables examined included body weight (BW), body mass index (BMI), blood pressure (BP), resting heart rate, total...
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Experimental use of selected cholesterol-lowering drugs as potential candidates in modification of the pathophysiology of Alzheimer's disease
Cibičková, Ľubica ; Bureš, Jan (advisor) ; Hlúbik, Pavol (referee) ; Jabor, Antonín (referee)
Rationale: The current standard treatment of Alzheimer's disease (AD) is represented by acetylcholinesterase (AChE) inhibitors. In the pathogenesis of AD, cholesterol is directly involved. Its blood and brain levels positively correlate with amyloid β (Aβ) - a peptide characteristic for AD and capable of increasing AChE activity. Based on these data, we may suppose that cholesterol-lowering medication such as statins and alendronate might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present studies was to investigate possible influence of two lipophilic statins (simvastatin and atorvastatin) and alendronate on cholesterol synthesis in selected parts of the rat central nervous system (CNS) and other parameters relevant to Alzheimer's disease pathophysiology. Methods: We have performed 3 similar experiments on awaked rats that were administered simvastatin, atorvastatin, alendronate or aqua. At the conclusion of experiments, blood and brain parts were isolated and analyzed for cholesterol, lathosterol, hydroxymethylglutaryl- coenzyme A reductase protein, acetylcholinesterase activity, amyloid beta (40 and 42) and cholesterol synthesis rate. Results: All drugs at higher doses were able to lower cholesterol in the plasma, but none...
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