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Kardiovaskulární onemocnění (dále KVO) jsou celosvětově nejčastější příčinou úmrtí u lidí starších 45 let, ovšem již u mladších jedinců dochází k předčasnému úmrtí na KVO. Cílem screeningového měření bylo stanovit relativní riziko úmrtí z kardiovaskulárních (dále KV) příčin v následujících 10 letech u studentů bakalářských studijních programů na fakultě zdravotnických studií Univerzity J. E. Purkyně (dále FZS UJEP). Vybrané rizikové faktory (krevní tlak, cholesterol) byly u zúčastněných studentů měřeny pomocí kalibrovaných přístrojů, zároveň tito studenti vyplňovali nestandardizovaný dotazník. Výzkumu se zúčastnilo celkem 185 studentů napříč všemi bakalářskými studijními programy ve věkovém rozmezí 19-25 let. Relativní riziko úmrtí z KV příčin bylo vypočítáno dle tabulky HeartScore pro mladé pacienty. Ze zjištěných výsledků vyplývá, že při abúzu kouření u 100 % studentů by bylo pouhých 10 % respondentů bez rizika úmrtí KVO a více jak 20 % ve středním a vysokém riziku úmrtí. V opačném případě (100 % probandů bez abúzu kouření) by až 80 % studentů bylo bez rizika úmrtí z KV příčin, ve zvýšeném a středním riziku 7 % a ve vysokém riziku žádný ze studentů.

The aim of this thesis is to verify the possibility of simultaneous determination of three structurally related biologically active substances (cholesterol, 7-dehydrocholesterol and cholecalciferol) after previous separation by high-performance liquid chromatography followed by electrochemical (on a boron-doped diamond electrode) and spectrophotometric detection, which were compared in this work. The influence of the water content in the mobile phase (in the range of 0-10 %) on the retention factor of the analytes and their response for both types of detectors was investigated. Using all mentioted water contents, the analytes baseline-separated. As the water content increased, the retention factor of the analytes increased as well as the background current for higher positive detection potentials. Based on the recorded hydrodynamic voltammograms, the optimum detection potential + 1.8 V was chosen. The optimum wavelength for spectrophotometric detection was 200 nm. The concentration dependence was measured in an of 50 mmol l−1 sodium perchlorate in acetonitrile mixed with water (95:5, v/v). The spectrophotometric detector provided lower detection limits compared with the electrochemical detector, which had detection limits of 2.3 μmol l−1 for cholesterol, 1.4 μmol l−1 for 7-dehydrocholesterol and...

The aim of this thesis is to investigate procedures leading to regeneration of boron- doped-diamond's (BDD electrode) surface and study of voltammetric behaviour of cholesterol and lanosterol on BDD electrode. Three options of regeneration of electrode's surface were were studied: the stirring, the mechanical polishing using alumina and the anodic oxidation. The anodic oxidation was studied using electrolytes: 0,1 mol l−1 perchloric acid in acetonitrile, 0,1 mol l−1 sodium perchlorate in acetonitrile and tetrahexylammonium hexafluorofosphate in acetonitrile. Each electrolyte was studied with 0 or 0,43 % and 20 % volume of water. Further, voltammetric behaviour of cholesterol on BDD electrode in the presence of 0,1 mol l−1 perchloric acid in acetonitrile was investigate. The second part of the thesis was the study of voltammetric behaviour of lanosterol on BDD electrode in the presence of 0,1 mol l−1 perchloric acid in acetonitrile and 0,1 mol l−1 sodium perchlorate in acetonitrile. The study was performed using cyclic voltammery. Lanosterol provides two anodic signals in the presence of both electrolytes, the first one at the potential of +1200 mV, the second one at the potential of +1500 mV. The stability of lanosterol in the presence of perchloric acid and sodium perchlorate was studied by...

This diploma thesis deals with home parenteral nutrition in the day and night regime and its effect on patients. Parenteral nutrition is usually administered at night so that patients can do normal daily activities and so that nutrition administered in this way has the least impact on their lives. Parenteral nutrition is not a physiological route of nutrient administration and it is not natural for the human body to process nutrients at night. The first part of the theoretical work presents parenteral nutrition and its composition, indications, contraindications and complications. The next part of the thesis describes home parenteral nutrition and its organisation which is necessary for this form of nutritional support to be implemented. It is necessary to monitor many laboratory values on parenteral nutrition, the theoretical part specifically mentions cholesterol, triacylglycerols, glycemia or liver function tests. One of the important parts is the chapter about circadian rhythms, hormones and metabolic changes in energy intake at night. Qualitative research was chosen for this work, which involved 17 patients on home parenteral nutrition. These patients were getting their nutrition during the night. Their laboratory values such as liver function tests, glycaemia and blood fats was evaluated and...

Cholesterol is an irreplaceable sterol found in animal cells, lathosterol is one of its precursors. The first aim of this Thesis is to develop a method for determining cholesterol after liquid- liquid extraction from milk matrices by differential pulse voltammetry on a boron doped diamond electrode in the presence of perchloric acid in acetonitrile where cholesterol provides an irreversible anodic response at the potential between +1300 and +1600 mV depending on the water content. The second aim is a study of the voltammetric behavior of lathosterol on boron doped diamond and glassy carbon electrodes using cyclic voltammetry and differential pulse voltammetry mainly in perchloric acid but also sodium perchlorate where lathosterol provides an irreversible anodic response at the potential of about +1650 mV on the boron doped diamond electrode and at the potential of +1350 mV on a glassy carbon electrode. The effect of other acids - sulfuric, nitric and phosphoric - on the response of lathosterol was also investigated. The influence of the water content in the measured solution and the influence of the polarization rate on the response of lathosterol were studied. Furthermore, the calibration dependence of lathosterol was measured using differential pulse voltammetry after optimization of its...

This bachelor thesis deals with vegetable oils that contain a higher proportion of saturated fatty acids. The aim was to determine their sources and impact on human health. This is a literature search that describes the classification of saturated fatty acids among lipids and informs about the most important saturated fatty acids. It also defines the most common vegetable oils with predominant stearic, palmitic or lauric acid. Last but not least, it describes their cultivation and subsequent processing into oil production. At the end of the thesis, diseases associated with saturated fatty acids are formulated, especially the increase in the level of LDL cholesterol and its effect on human health. Overall, the topic of lipids and saturated fatty acids has not been fully explored and contradictory studies are emerging on how they affect human health and how they should be reduced in the human diet.

Lipids are an essential components of cell membranes and their homeostasis plays an important role in the development of Alzheimer's disease. The aggregation and neurotoxic effects of amyloid β, mainly Aβ42, on the neural cell membrane are crucial for pathological changes in the brain tissue which leads to its degeneration and loss of cognitive functions. The complex relationship between amyloid β and lipids is also supported by fact that membrane lipids do not only support the amyloid binding to the membrane, but also they regulate the splicing of the amyloid precursor protein, therefore the biosynthesis of β amyloid. The most important binding partners of Aβ42 include gangliosides, especially the ganglioside GM1, but also sphingomyelin and cholesterol. In contrast, glycerophospholipids primarily affect the process of the protein production.

Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Pavla Audrlická Supervisor: prof. PharmDr. Kateřina Vávrová, Ph.D. Title of diploma thesis: Study of cholesterol depletion in human skin barrier Barrier function of human skin barrier dwells in intercellular lipid membranes of the uppermost skin layer, the stratum corneum (SC), composed of equimolar mixture of ceramides (Cer), free fatty acids (FFA) and cholesterol (Chol).1 Chol is required for proper lipid organization of SC, however, it stays unclear, why is it present in an amount so high that it separates from other lipids.2 Experiments using synthetic model membranes with decreased Chol content suggested that molar ratio of Cer:FFA:Chol 1:1:0,4 is sufficient for lipid barrier formation and its complex functionality.3 The aim of this work was to manipulate Chol content directly in human SC and to study the effects of decreased Chol content on the SC permeability and microstructure. Ex vivo SC obtained from healthy donors was extracted by methyl-β-cyclodextrin (MCD) to reduce natural Chol content. The extracted SC did not show significant changes in Cer or FFA whilst the amount of Chol was lowered to 78 %. SC barrier properties were evaluated by measurements of transepidermal water loss...

Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Pavla Audrlická Supervisor: prof. PharmDr. Kateřina Vávrová, Ph.D. Title of diploma thesis: Study of cholesterol depletion in human skin barrier Barrier function of human skin barrier dwells in intercellular lipid membranes of the uppermost skin layer, the stratum corneum (SC), composed of equimolar mixture of ceramides (Cer), free fatty acids (FFA) and cholesterol (Chol).1 Chol is required for proper lipid organization of SC, however, it stays unclear, why is it present in an amount so high that it separates from other lipids.2 Experiments using synthetic model membranes with decreased Chol content suggested that molar ratio of Cer:FFA:Chol 1:1:0,4 is sufficient for lipid barrier formation and its complex functionality.3 The aim of this work was to manipulate Chol content directly in human SC and to study the effects of decreased Chol content on the SC permeability and microstructure. Ex vivo SC obtained from healthy donors was extracted by methyl-β-cyclodextrin (MCD) to reduce natural Chol content. The extracted SC did not show significant changes in Cer or FFA whilst the amount of Chol was lowered to 78 %. SC barrier properties were evaluated by measurements of transepidermal water loss...

This bachelor thesis is focused on the effect of weight reduction on the level of total cholesterol, triglycerides, waist circumference and blood pressure. The effect of education, or changes in dietary and regime habits on weight, blood lipid levels (total cholesterol and triglycerides), waist circumference and blood pressure were monitored in a group of educated persons. The work is divided into two parts. The theoretical part contains information about obesity, ischemic heart disease, risk factors for these diseases, their prevention and therapy. The practical part of the bachelor's thesis is devoted to monitoring dedicated a group of patients who decided to lose weight by changing dietary and dietary habits. At baseline, patients were measured on by the Accutrend for total cholesterol, triglycerides, waist circumference, and blood pressure. The subjects were educated about the dietary regime and subsequently followed the recommended measures. Repeated measurements of all monitored indicators were performed after three months, when the effect of weight reduction on the monitored parameters was evaluated. After three months, all subjects demonstrated on average weight loss of 11.9 kg, BMI lowered by 3.94 kg / m2, and waist circumference parameters reduced on 8.9 cm. Systolic pressure decreased by...

Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Student: Marie Šimková Supervisor: Mgr. Alena Prašnická Title of diploma thesis: Alternation of bile production due to iron depletion Introduction: Liver has an irreplaceable role in the production and secretion of bile. This body fluid serves as the main excretion way of some endogenous and exogenous substances. Another liver property is the ability to store substances essential for correct functions of the body, e.g. iron. It has been shown that iron could have an impact on the bile production and secretion. Aim: The aim of this diploma thesis was to discover an impact of iron depletion on the bile synthesis and metabolism, especially on bile acids, and the way it affects transporters expression. Methods: Male Wistar rats (n=6 in each group, 250 ± 20 g) were divided into two groups: control group (Chow diet) fed with standard diet and iron depletion group (ID), fed with iron depletion diet for 21 days. To investigate the changes in bile flow, the bile had been collected for 120 min during in vivo clearance study. The analysis of the changes in expression of bile transporters and enzymes responsible for de novo bile acid synthesis was performed at the mRNA (qRT-PCR) and protein (Western blot)...

The aim of this Thesis is a study of voltammetric behaviour of cholesterol on glassy carbon electrode in the presence of acetonitrile and strong acid. The electrochemical oxidation occurs after dehydration of cholesterol induced by the acid. The study was performed using cyclic voltammetry, mostly in the presence of perchloric acid. Further, influence of other acids - sulphuric, nitric and phosphoric acid - was studied. Cholesterol provides in the presence of perchloric and sulphuric acid one anodic signal at the potential of +1400 mV vs. Ag/0,01 mol.l-1 AgNO3 in 1 mol.l-1 NaClO4 in acetonitrile. The influence of polarization rate, water content and concentration of perchloric acid in the supporting electrolyte on the oxidation signal of cholesterol was studied. Calibration dependence of cholesterol was measured using differential pulse voltammetry. The limit of detection was determined to be 4,83.10-6 mol.l-1 . Key words: Dehydration, glassy carbon electrode, cholesterol, oxidation, voltammetry

There is a lot of factors which has impact on quality of bovine meat. The aim of this thesis was to examine correlations between chosen SNPs in leptin gene and specific hormones and metabolites, which have influence on the meat quality and also complete health condition of beef. There were 99 bulls of Czech Fleckvieh cattle used for this study. The examined parameters were insulin, glucose, cholesterol, triacylglycerol, non-esterified fatty acids and betahydroxybutiric acid. There was shown no statistically signifiant correlation between leptin gene polymorfisms and observed parameters. Only proved correlation was between leptin and cholesterol and glucose. There is lot of other factors involved in changes of amount of these substances though.

PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time. Due to high efficiency of PCSK9-inhibitors lowering LDL-C, but also their lower cost as compared to therapeutic LA, PCSK9-inhibitors now take precedence over the use of extracorporeal lipoprotein apheresis which, nonetheless, still remains the final method for hypolipidemic treatment of patients with severe hypercholesterolemia, who are resistant to conventional therapy while not reaching the target lipid values and at high cardiovascular risk. They belong to extracorporeal elimination methodologies which remove low density lipoprotein (LDL) cholesterol from circulating blood. LA in combination with higher doses of statins and ezetimib currently represents the most efficient method of treatment of homozygous and statin-refractory heterozygous familial hypercholesterolemia (FH). Residual cardiovascular risk in these patients still remains high, in particular because, despite the aforementioned treatment, the target values for lipids according to present recommendations cannot be reached. The combination of LA with the new drugs is promising, primarily due to its potential for further lowering of LDL-cholesterolemia between the individual apheresis procedures. Preliminary results of the ongoing studies indicate that the new hypolipidemic drugs in combination with LA, or when used separately, will substantially enrich and improve the treatment of refractory FH.Key words: alirocumab - atherosclerosis - evolocumab - hypercholesterolemia - cardiovascular disease - lipoprotein apheresis.

The Bachelor thesis is focused on eating of patients suffering from hypercholesterolemia. The main goal of Bachelor thesis was to find out how patients with hypercholesterolemia eat and what impact to the cholesterol level does the change of eating habits have. The thesis is divided into theoretical and practical part. The theoretical part describes the basic food ingredients, cholesterol and characteristics of hypercholesterolemia, its types, risk factors influencing its development, treatment options and prevention of the illness. It deals with the influence of individual food ingredients to cholesterol level and diet measures to decrease cholesterol level in blood. In conclusion the theoretical part describes atherosclerosis, which is closely related to hypercholesterolemia. The practical part was created by a qualitative research using semi-structured interviews. Interviews were lead with six patients suffering from hypercholesterolemia with high concentration of cholesterol in blood. Then the patients were instructed to record their menus for one week. I entered these menus into "Nutriservis Professional" program, which helped me evaluate them and thanks to this I was able to determine the average cholesterol intake in a patient's diet. Then I gave the patients a diet recommendation they should follow for the next six months. After this period, patients were asked to check their cholesterol level again, which helped me to find out the influence of the diet to level of cholesterol. It can be seen from the results of the research that in case the diet is kept, and a physical activity is included into a normal life, the patients can successfully decrease cholesterol level in blood. We can notice that most patients exceeded the recommended 300mg daily dose of cholesterol. The Bachelor thesis can serve as a teaching material for patients suffering from hypercholesterolemia, but it can also serve to increase knowledge about this disease.

Cholesterol is a substance of a steroidal nature that has a number of functions in the human body. One of them is also an irreplaceable role in the proper functioning of the skin barrier. Cholesterol is an integral part of the lipid matrix, together with ceramides and free fatty acids in an equimolar ratio (1: 1: 1), and 5% cholesterol sulfate, which fills the intercellular space between stratum corneum cells and is responsible for the barrier properties of the skin. Cholesterol is therefore necessary for epidermal homeostasis, but its role in SC permeability is unknown. The aim of this work was to study the influence of cholesterol concentration on the permeability and microstructure of model lipid membranes of the skin barrier. Eight sets of model membranes with decreasing cholesterol concentrations (100%, 80%, 70%, 60%, 40%, 20%, 0%) and cholesterol alone were studied for which permeability and microstructure were monitored.The study of permeability of membranes was carried out in the Franz diffusion cells by measuring four permeation parameters: water loss, electrical impedance measurement, and the cumulative amount of two model drugs (theophylline and indomethacin). The microstructure of these model membranes was verified by X-ray powder diffraction. X-ray powder diffraction measurements...

The bachelor thesis describes the influenceable risk factors of ischemic stroke. The main objective of thesis was to compare knowledge about higher mentioned factors between two groups of respondents. First group includs patients with high risk for developing stroke. Second one is composed of those patients, who was already treated after stroke developed. This research question led us to fulfill the objective: Is there any diference in knowledge of two mentioned groups of respondents above? For the research realization we applied quality approach through a semi-structured interview. The background for the interview (annex 1) consisted of nine questions. The main questions have been developed with supplementary questions. The first four question were clarified by a stroke. There were also questions about lifestyle. The data obtained from the research was subsequently processed by open-coding using pencil and paper. The research team consisted of 10 respondents, with 5 respondents in the high risk group of the stroke and the remaining 5 respondents. after a stroke of the ischemic type. The results of the work were divided into thematic categories and subcategories for better clarity. Answers from respondents from a qualitative research survey suggested that patients with a high risk of CMP are less well-targeted than CMP patiens. All patients are dispensed by a physician. It is clear that these results may indicate a low level of primary prevention, notably awareness of this disease and a low level of health literacy overall All patients go to the doctor regularly. It is clear that these results may indicate a low level of primary prevention, especially awareness of this disease and a low level of health literacy.

The aim of this Thesis is development of electroanalytical methods for determination of cholesterol and 7-dehydrocholesterol on boron doped diamond electrodes based on electrochemical oxidation of products of acid-induced dehydration reaction. Two approches have been applied, relying on their detection in 0,1 mol.l-1 perchloric acid in acetonitril containing variable water content 0,43 % - 40 %. Cyclic voltammetry revealed substantial difference in oxidation peak pontecials for 7-dehydrocholesterol (+850 mV) and cholesterol (+1500 mV) in 0,1 mol.l-1 perchloric acid in acetonitrile containing 5 % of water. The limit of detection using differential pulse voltammetry were 6,19 µmol.l-1 a 19,2 µmol.l-1 for a mixture of 7-dehydrocholesterol and cholesterol, respectively. For flow injection analysis with amperometric detection (FIA-AD) the water content in run buffer, detection potencial and the distance between the capillary outlet and electrode surface in wall-jet arrangement of amerometric flow-through detection cell were optimized. Achieved detection limits are in range of 0,61 - 3,43 µmol.l-1 depending on the detection potencial and water concent in the run buffer. The developed FIA-AD method was used for determination of a model mixture solution of 7- dehydrocholesterol and cholesterol. Key words...

If we want to favorably influence the cardiovascular atherosclerotic disease, it is necessary to significantly lower LDL-C blood levels. PCSK9 inhibitors can significantly reduce LDL-cholesterol levels, being administered together with statins. However we focus on establishing whether this plays a role in influencing coronary atherosclerosis. The GLAGOV study is a multicentric, double-blinded and placebo-controlled study which during a 76-week period followed an impact of the treatment with evolocumab (PCSK9i) together with statin on the status of coronary atherosclerosis in patients with ischemic heart disease, and in comparison with the statin treatment. 968 patients at an average age of 60 have reached a significant decline in the levels of serum LDL-cholesterol (from 2.39 to 0.95 mmol/l) in the branch of the combined therapy, which led to a considerable reduction of percent atheroma volume in the coronary artery by 0.95% (in the branch of the statin-only therapy, the percent atheroma volume increased by 0.05%). The therapy was safe. As shown by the results, evolocumab can through additional reduction of blood levels of LDL-C favorably influence (reduce) coronary atherosclerosis.Key words: evolocumab - regression of coronary atherosclerosis - LDL-C blood levels.

The aim of this opinion is to summarize and to comment the consensus of the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine, which covers two main areas: 1) whether it is necessary / required to be fasting or non-fasting before blood sampling for lipids measurement, and what are the changes in the concentration of blood lipids during the day; 2) What decision limits (cut off value) of lipids and lipoproteins should be reported from laboratories and what is the recommended procedure for people with extreme / critical blood lipid values. Following parameters are discused: total cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein(a). This opinion should be the object of interest both for professionals in clinical laboratories and for physicians in hospitals and out-patients departments.Key words: apolipoproteins - blood collection - cholesterol - laboratory testing - lipoprotein(a) - cut off limits - triglycerides.

Hyperlipoproteinemia (HLP) and dyslipidemia (DLP) are of course mainly perceived as diseases of common incidence and are typically seen as the greatest risk factors (RF) in the context of the pandemic of cardiovascular diseases. This is certainly true and HLP or DLP overall affect tens of percents of adults. However we cannot overlook the fact that disorders (mostly congenital) of lipid metabolism exist which, though not formally defined as such, amply satisfy the conditions for classification as rare diseases. Our account only includes a brief overview of the rare HLPs based on the dominant disorder of lipid metabolism, i.e. we shall mention the rare primary forms of hypercholesterolemia, primary forms of hypertriglyceridemia and the rare primary combined forms of HLP. In recent years an amazing progress has been reached relating to these diseases, in particular in the area of exact identification of the genetic defect and the mechanism of defect formation, however each of these diseases would require a separate article, though outside the field of clinical internal medicine. Therefore we shall discuss homozygous familial hypercholesterolemia (FH) in greater depth, partially also the "severe" form of heterozygous FH and in the following part the lipoprotein lipase deficiency; that means, diseases which present an extreme and even fatal risk for their carriers at a young age, but on the other hand, new therapeutic possibilities are offered within their treatment. An internist then should be alert to the suspicion that the described diseases may be involved, know about their main symptoms, where to refer the patient and how to treat them. Also dysbetalipoproteinemia (or type III HLP) will be briefly mentioned. Homozygous FH occurs with the frequency of 1 : 1 000 000 (maybe even more frequently, 1 : 160 000), it is characterized by severe isolated hypercholesterolemia (overall cholesterol typically equal to 15 mmol/l or more), xanthomatosis and first of all by a very early manifestation of a cardiovascular disease. Myocardial infarction is not an exception even in childhood. The therapy is based on high-dose statins, statins in combination with ezetimib and now also newly on PCSK9 inhibitors. Lomitapid and partly also mipomersen hold great promise for patients. LDL apheresis then represents an aggressive form of treatment. Lipoprotein lipase deficiency (type I HLP) is mainly characterized by severe hypertriglyceridemia, serum milky in colour, and xanthomatosis. A fatal complication is acute recurrent pancreatitis. A critical part of the treatment is diet, however it alone is not enough to control a genetic disorder. The only approved treatment is gene therapy. Experimentally, as an "off label" therapy, it is used in case studies with a lomitapid effect. We have our own experience with this experimental therapy. Dysbetalipoproteinemia is a congenital disorder of lipoprotein metabolism, characterized by high cholesterol (CH) and triglyceride (TG) levels. The underlying cause of this disease is the defect of the gene providing for apolipoprotein E. It is clinically manifested by xanthomatosis, however primarily by an early manifestation of atherosclerosis (rather peripheral than coronary).Key words: Lipoprotein lipase deficiency - dysbetalipoproteinemia - familial hypercholesterolemia - gene therapy - homozygous FH - LDL apheresis - lomitapid - mipomersen - PCSK9 inhibitors - rare diseases.

Atherosclerosis or cardiovascular disease is the leading cause of mortality and morbidity in developed countries. Intervention of its risk factors is pharmacological but non-pharmacological intervention must be its integral part. Dietary recommendations for dyslipidemia are long known however it is necessary to emphasize the importance of their compliance. Presently, these recommendations for adult population to prevent from atherosclerosis are based on healthy nourishment, especially to have sufficient consumption of fish, fresh vegetable and fruit and to avoid consumption of secondary processed meat especially, i.e. smoked meat. Nowadays, there is a diverting trend from recommendation to strictly avoid cholesterol in the diet.Key works: atherosclerosis - cholesterol - diet intervention - dyslipidemia - fatty acids.

Cholesterol 7-hydroxylase (CYP7A1) is the rate limiting enzyme of the classical pathway of bile acid (BA) synthesis, which catabolizes approximately half of cholesterol in man. Determination of CYP7A enzymatic activity is a key subject of lipid metabolism research. Direct determination of CYP7A1 activity in hepatic biopsy is mostly not allowed for ethical reasons, so indirect methods are used with serum markers such as 7α-hydroxy-4-cholestene-3- one (C4). The first, methodical aim of the work was to convert the introduced HPLC method for the determination of C4 to LC-MS in order to increase the sensitivity. We focused on the solid phase extraction step, adjusting the composition and volumes of the washing and elution solution. By converting the method from HPLC to LC-MS, the sensitivity was increased approximately 7 times (LD = 1.39 ng/ml). In the second, clinical part of our work, we attempted to confirm the preliminary results of our laboratory on the distribution of C4 in lipoprotein fractions (LPP) in order to find parameter that would correlate with CYP7A1 activity better than C4 level itself. Preliminary results (performed in healthy individuals) showed that most of C4 is carried on HDL, and that the C4 distribution within LPP fractions is similar among examined subjects. We repeated the...

In this bachelor thesis I mainly focused on the role of fats and oils along with cholesterol in human nutrition. At first I described nutrient composition of food, thus macronutrients and micronutrients and after describing those major food components I followed by describing lipids, where I predominantly focused on their most abundant part in food which consists of fats and oils. In this part I specified fatty acids and divided them according to the degree of their saturation. Next I described phospholipids and one of the accompanying substance of lipids, thus cholesterol, where I specified its natural occurence in food, metabolism, transport by lipoproteins and its importance in human body and nutrition. I also mentioned serious degenerative disease which can be caused by excess consumption of the wrong type of fatty acids. Last but not least I applied acquired knowledge to discuss the possibilities of influencing the level of total serum cholesterol and its HDL and LDL fraction by the type of consumed fatty acids and the amount of consumed cholesterol.

The thesis deals with trends of drug consumption for the ATC group C10A (HMG-CoA reductase) in the Czech Republic in the years 2005 - 2015. The goal of this work is to analyse the consumption of statins (cholesterol lowering drugs), as well as to analyse the consumption trends (expressed in terms of prescribed daily doses) and subsequently explain the causes of the detected trends. The main method used in this work is the analysis and interpretation of data provided by the State Institute for Drug Control (SUKL). Individual consumption data sets are compared to each other and global trends are inferred based on the obtained results. In the practical part I analyse the consumption for the individual ATC groups according to their increasing lipid-lowering efficacy, according to the pharmaceutical companies involved and according to the experts' recommendations (within the framework of cardiovascular disease treatment). The conclusion of my work shows that the overall drug consumption for the the studied ATC group (given by the DDD/package total) was steadily increasing during the studied period while the consumption expressed in financial units was decreasing (ie. the financial burden on the health system was reduced). The total number of sold packages shows a slight decrease due to the sale of bigger packages with more powerful statins during the studied period.

Bordetella pertussis produces many virulent factors including adenylate cyclase toxin (CyaA) This toxin preferentially invades cells of immune system with integrin receptor CD11b/CD18 and weakens the immune system of the host. CyaA affects invaded cells in two ways. First, CyaA creates a cation-selective pores in the membrane of invaded cell and causes colloidal osmotic lysis. Second, CyaA converts cytosolic ATP into signal molecule cAMP, which causes a loss of physiological function of invaded cell and also leads to cellular death. The aim of my thesis was to test a suitability of a new model system composed from synthetic lipids - diphytanoyls, for a characterization of pore-forming properties of adenylate cyclase toxin. In the past, asolectin model system comprising many different lipid was used for characterization but it was found to be too complex for defining the role of individual lipids in CyaA activity. Further the effect of cholesterol for activity of CyaA was studied in a new model system because it was found recently that translocation of adenylate cyclase domain takes place at lipids rafts with high concentration of cholesterol. The last aim of my thesis was to characterize a newly discovered type of channel with the two conductance levels. Key words: Bordetella pertussis, adenylate...

The bachelor thesis examines the influence of education and diet on patients with dyslipidemia. Another object was to explore the eating habits of patients and find out if they are interested in a healthy lifestyle. The theoretical part is based on knowledge from the academic literature. It explains the concept of dyslipidemia, its divisions and causes of disease and describes possible methods of treatment. The pieces of information for the practical part are obtained through questionnaires from patients who are treated in the Center for Preventive Cardiology, 3rd Department of Internal Medicine, 1st Medical Faculty of Charles University in Prague. Another source are laboratory tests of blood, which were taken before education and then again after a minimum interval of one month from the education. Values were processed by using graphs and tables. The results clearly showed us that after education and compliance with the recommended diet, values of blood lipids were improved. On three of the four monitored lipid parameters diet had a positive impact. Furthermore, it appears that the majority of patients with dyslipidemia has good eating habits. The last point that has been studied, was the patients' interest in a healthy lifestyle. It revealed insufficinet interest at the majority of the...

In my bachelore thesis I describe an origin of atherosclerosis disease. It is a disease caused by various risk factors, which interaction enhaces emergence of atherosclerosis. Some of these factors are determined or conversely accelerated, depending on a lifestyle of an individual. This work describes dietary interventions for avoiding atherosclerotics vascular changes, which eliminates development of serious chronic illness atherosclerosis.

Europe is a region, which is most severely affected by non-communicable diseases. Cardiovascular disease is the leading cause of disability and death. Complex interactions between diet, lifestyle, and lipoprotein metabolism significantly contribute to the development of atherosclerosis and its complications. Role of diet in prevention of coronary heart disease becomes sometime underestimated in comparison with pharmacological treatment. Coronary heart disease (CHD) mortality has declined substantially in the Czech Republic in the last decade of the 20th century. Significant and positive dietary changes, mainly reduction of saturated fatty acids intake and its replacement by polyunsaturated fatty acids, contributed to decline of the average serum cholesterol level in population. Fall in CHD mortality was attributable to reduction in this major cardiovascular risk factor and not driven by pharmacological intervention. The Czech Republic is not the only country where similar trends have been recorded. Improvements in dietary habits seem to be one of the most important strategies in cardiovascular disease prevention.

Currently, the familial hypercholesterolemia (FH) rises the interest. The reason is that this genetic disorder is targeted by newly emerged and highly effective hypolipidemic agents, PCSK-9 inhibitors, lomitapid and mipomersen. Present paper discusses 2 patient study groups, before 50 years and nowadays. Although direct statistical analysis is impossible some changes in clinical features of FH might be found over the course of the time. In fact, the basic FH characteristic has not changed dramatically. Severe isolated hypercholesterolemia with total cholesterol 9-10 mmol/l, LDL-cholesterol 7-8 mmol/l and normal values of triglycerides dominates in laboratory analysis. Interestingly, the values of triglycerides increase and almost reach the pathological range in comparison to the values from the period 50 years ago. The values of HDL-cholesterol are normal. Manifestation of CHD in male patients over 40 years of age and in female patients over 50 years of age is not exceptional (rarely occur cases of myocardial infarction in third decade of age). Typical clinical manifestation of FH is xanthomatosis. The early detection and aggressive treatment in FH patients cause that xanthoma tendinosum, xanthelesma and arcus lipoides are less frequent as decades ago. Obesity, diabetes mellitus (DM) and hypertension do not belong to typical clinical sign of FH.

This bachelor's thesis is focused on animal fat consumption of patients with cardiovascular disease (CVD) and diabetes mellitus (DM). Content of thesis is divided into theoretical and practical part. The main objective of theoretical part is to provide a general description of lipids in terms of distribution, structure, characteristics and their role in human organism. In the following chapters metabolism and transport of lipids is described with more attention to details. The last part of theoretical part deals with animal fats in nutrition, mostly risk factors as a consequence of their increased consumption, and dietary measures as a prevention and therapy of CVD and DM. The practical part of bachelor's thesis is based on assessment survey. The object of this survey was the evaluation of eating habits, mainly the measure of animal fats consumption of patients with CVD and DM. Next object of interest was the evaluation of awareness, knowledge and education these patients have about dietary measures in relation to their disease. Question about the way how are these measures followed by patients was also examined. The survey was conducted in the diabetological center and also in the centre of preventive cardiology of General Teaching Hospital in Prague on patients with CVD and DM. Key words: lipids,...

My bachelor thesis is called ,,Food for people with hypercholesterolemia", and it focuses on cholesterol intake and its impact on the human body. The main aim of this thesis was to map the diet of people with hypercholesterolemia regarding both, quality and quantity of meals. The first part of this thesis is theoretical. It focuses on the description of basic nutritional components, on the issue of fat and cholesterol in the diet, on the characteristics of hypercholesterolemia disease, its classification, causes of development of this disease, treatment options and prognosis. The risk factors which lead to the hypercholesterolemia disease development, dietary restrictions, and some examples of low cholesterol and low fat diet menus are also mentioned in the first part of thesis. The practical part of this thesis was done as a qualitative and quantitative research. Qualitative research was conducted using the snowball method from February to March. Selected respondents recorded their diet for the period of one week. The diet was recorded in the record sheets which I evaluated after they were filled in and returned back to me. I entered all of the foods mentioned in the diet record sheets into the program ,,Nutriservis Prefesional", which helped me to calculate average intake of energy, fats, cholesterol, proteins and carbohydrates during the reference period. I also submitted questionnaire to examine eating habits, diseases and physical parameters of my respondents. The questionnaire was focused mainly on the frequency and quantity of food with high cholesterol. Then I determined the ideal weight according to BMI index for every respondent and from the ideal weight I calculated the ideal intake of calories, fats, proteins and carbohydrates per day. I compared ideal values of energy, macronutrients and cholesterol of each respondent with average values recorded during the research. The research revealed that most respondents have a diet with larger quantities of cholesterol than the recommended daily dose i.e. 300 mg of cholesterol per day.

The bachelor thesis is focused on the relationship of eating habits and dyslipidemia. Its aim is to find out whether diet influences blood lipid levels. The paper is divided into a theoretical and a research part. The theoretical part handles with lipids of the human organism in general, their metabolism and the risks of atherosclerosis. The research part describes work with patients who suffer from lipid metabolism disorders. The patients had a diet consultation and, two months after, they had their blood drawn to see the results of cholesterol and triglycerides levels. The patients also filled in a questionnaire concerning their eating habits. It turned out that nutritional intervention had resulted in an average decrease in triglycerides and total as well as LDL-cholesterol levels. However, HDL-cholesterol level decreased as well. Furthermore, the questionnaire enquiry showed that dyslipidemic patients do not, in general, disobey recommendations of the dyslipidemic diet. The results of the paper showed that dyslipidemic patients follow recommendations of a healthy diet. However, there is still space for improvement. Thus, regular diet consultations are important and can help improve state of health of dyslipidemic patients. Keywords: Diet, dyslipidemia, cholesterol, triglycerides

The new malformation syndrome was first described approximately 50 years ago in three unrelated patients in Department of Pediatrics at the University of Wisconsin, Madison, (Smith, Lemli, Opitz 1964). This syndrome was called RSH syndrome after the first 3 patients studied. First Slovak patient with phenotypic features of this new syndrome was described by professor Sršeň in 1972. In 1994 Tint from VA Medical Center, E. Orange, New Jersey analyzed plasma sterols of patient with Smith-Lemli-Opitz syndrome and found out that in addition to low plasma cholesterol level, the patient had 1000-fold increase of the plasma level of 7-dehydrocholesterol, the immediate precursor of cholesterol biosynthesis. After this biochemical discovery Smith-Lemli-Opitz syndrome became the metabolic-malformation syndrome with an exactly defined impairment of cholesterol metabolism. The first patient with biochemically proved Smith-Lemli-Opitz syndrome in Slovakia was described by Behulova et al. (1997) in cooperation with Department of Biochemistry and Medical Biotechnology, Federico II University in Naples, Italy. The three years later a screening method UV spectrometry of serum lipids for detection of 7-dehydrocholesterol was established in Department of Biochemistry, University Children´s Hospital in cooperation with the Institute of preventive and clinical medicine in Bratislava (Skodova et al.,2000). First results of molecular analysis of the 7-dehydrocholesterol reductase gene in 10 unrelated Czech and Slovak patients with Smith-Lemli-Opitz syndrome were reported by Kozak et al. (2000). The same year the first prenatal diagnosis of Smith-Lemli-Opitz syndrome by mutation analysis was achieved (Bzduch et al., 2000). Our research activities on this topic drew good response from abroad.

Metabolic syndrome is a prevalent disease characterized by concurrent manifestation of insulin resistance, obesity, dyslipidemia, hypertension and other hemodynamic and metabolic disorders. It has multifactorial type of inheritance and its resultant phenotype is determined by both environmental and genetic factors as well as their interactions. That is the main reason why comprehensive analysis of the genetic component of this syndrome is complicated in human population. Genetically designed experimental animal models are significant tools for analysis of genetic architecture of human complex conditions including the metabolic syndrome. The aim of this Thesis is utilization of functional and comparative genomic tools to uncover pathogenesis of metabolic syndrome aspects and their genetic determinants. We also studied pharmacogenetic interactions of these genetic determinants with drugs affecting particular components of the metabolic syndrome. Establishing and utilizing several genetically designed congenic rat strains, we undertook four different research projects focusing on pharmacogenetic interaction of all-trans retinoic acid and ondansetron with differential segment of rat chromosome 8, pharmacogenetic interaction of differential segment of rat chromosome 4 and dexamethasone, determining Plzf...

Changes in lipid metabolism in acute diseases. Introduction. Abnormalities in lipid metabolism have been described in critically ill patients repeatedly. While triglycerides behave unpredictably, decrease of cholesterol levels is a typical finding. Further, low levels of cholesterol in critically ill patients have been found to be associated not only with poor prognosis but also increased mortality. Cholesterol is derived in two ways: via de novo synthesis and via dietary absorption. Both the modalities can be monitored by the determination of CH synthesis markers (lathosterol, squalene in blood plasma), and cholesterol absorption markers (sitosterol and campesterol in blood plasma) Material and method: In the first project sixty patients with acute internal disease were involved and their lipid profile was evaluated. Second and third projects have solved the same problem in the group of patients with active Cohn's disease (n=24) and acute upper gastrointestinal bleeding (n=24). Serum concentrations of total, LDL and HDL cholesterol and triglycerides were measured in an enzymatic automated system. Non-cholesterol sterols (lathosterol, squalene, sitosterol, campesterol) were analysed using gas chromatography - mass spektrometry. The data were statistically analysed by the statistical software Sigma Stat 3,1....