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The influence of LDL-apheresis on aggregation of blood platelets, blood coagulation, and the effect of standard drugs.
Černotová, Veronika ; Mladěnka, Přemysl (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Černotová Supervisor: prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Lukáš Konečný, MSc. Title of diploma thesis: The influence of LDL-apheresis on aggregation of blood platelets, blood coagulation and the effect of standard drugs LDL-apheresis is a method that removes LDL-cholesterol (LDL-C) from the blood. It is used to treat familial hypercholesterolemia (FH), a genetic disorder causing high LDL-C levels and an early development of cardiovascular diseases. Blood platelets and coagulation system play an important role in these diseases and their activity is also affected by lipids. The aim of this thesis was to analyze possible differences in platelet aggregation and blood coagulation in patients suffering from FH. Two methods of treatment in this group were compared - lipid apheresis and PCSK9Ab (proprotein convertase subtilisin/kexin type 9 monoclonal antibodies). The observed parameters were also compared with age-matched healthy volunteers. Our cohort consisted of 15 patients and 15 healthy donors. Six patients were treated with lipid apheresis and also PCSK9Ab, six subjects only with PCSK9Ab. Platelet aggregation was measured with an impedance aggregometer using 7 different...
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New diagnostic and therapeutic approaches for the prevention of CVD in patients with familial hypercholesterolaemia
Altschmiedová, Tereza ; Češka, Richard (advisor) ; Rosolová, Hana (referee) ; Rašlová, Katarína (referee)
Atherosclerotic cardiovascular diseases are still the most common cause of death in Europe, despite new diagnostic methods and treatment. Although many accelerators of the atherosclerotic process are known, only LDL-cholesterol is considered to be the causal risk factor for atherosclerosis. Familial hypercholesterolaemia (FH) is an autosomal dominantly inherited disease whose carriers have had a high level of LDL-cholesterol since childhood due to reduced amount or function of LDL receptors . Determination of the causative mutation is not always possible and the diagnosis is established by using some scoring systems which take into account personal and family history and some typical signs (e.g. tendon xanthomas) in addition to LDL-cholesterol value. The treatment of FH is lifelong and to achieve the LDL- cholesterol target, combination therapy (ezetimibe, modern biologic therapy) in addition to statins , is often necessary. However statins are always the mainstay of the treatment. By retrospective analysis of data from 1236 patients diagnosed with FH, we confirmed the cardiovasular risk of these patients is different depending on the presence of other risk factors. At the highest cardiovascular risk were individuals with combination of risk factors - high level of LDL cholesterol and total cholesterol, as...
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Genetic factors of familial hyperlipidemia and prevention of cardiovascular diseases
Todorovová, Veronika ; Češka, Richard (advisor) ; Blaha, Vladimír (referee) ; Karásek, David (referee)
Familial hyperlipidemias are still a current cause of premature development of atherosclerotic cardiovascular disease (ASCVD). Heredity plays an important role in the development of these diseases. Genetic testing helps to specify a definite variant of a given disease and thus the degree of genetic family burden. Together with the clinical examination, it defines the exact diagnosis of the patient and reduces the risk of developing ASCVD in individual specialized care. In the theses, we focused on biochemical and genetic differences and their risk factors for the development of ASCVD in long-term monitored patients with familial hypercholesterolemia (FH), in receptor-mediated FH and familial defect of apolipoprotein B- 100 (FDB). Efficacy, safety, and tolerability of therapy were evaluated in a subgroup of FH patients with PCSK9i therapy. Furthermore, the polygenic genetic risk score (GRS) in patients with the APOE2E2 genotype and its influence on the early detection of the development of familial dysbetalipoproteinemia (FD) were analyzed. Receptor-mediated FH patients carry a mutation in LDLR while FDB patients have a prevalent mutation in APOB. LDL-C and TC levels are high in both groups, although levels are slightly higher in receptor-mediated FH patients. APOE genotype and risk factors such as...
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The influence of LDL-apheresis on aggregation of blood platelets, blood coagulation, and the effect of standard drugs.
Černotová, Veronika ; Mladěnka, Přemysl (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Černotová Supervisor: prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Lukáš Konečný, MSc. Title of diploma thesis: The influence of LDL-apheresis on aggregation of blood platelets, blood coagulation and the effect of standard drugs LDL-apheresis is a method that removes LDL-cholesterol (LDL-C) from the blood. It is used to treat familial hypercholesterolemia (FH), a genetic disorder causing high LDL-C levels and an early development of cardiovascular diseases. Blood platelets and coagulation system play an important role in these diseases and their activity is also affected by lipids. The aim of this thesis was to analyze possible differences in platelet aggregation and blood coagulation in patients suffering from FH. Two methods of treatment in this group were compared - lipid apheresis and PCSK9Ab (proprotein convertase subtilisin/kexin type 9 monoclonal antibodies). The observed parameters were also compared with age-matched healthy volunteers. Our cohort consisted of 15 patients and 15 healthy donors. Six patients were treated with lipid apheresis and also PCSK9Ab, six subjects only with PCSK9Ab. Platelet aggregation was measured with an impedance aggregometer using 7 different...
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Comparison of eating habits of patients with familial hypercholesterolemia and mixed dyslipidemia
Holubová, Šárka ; Šnejdrlová, Michaela (advisor) ; Altschmiedová, Tereza (referee)
This bachelor thesis deals with eating habits of patients with two metabolic diseases, familial hypercholesterolemia and mixed dyslipidemia. The thesis is divided into two parts. The first theoretical part summarizes information on metabolic disease, types of treatment and dietary measures. The second, practical part is also divided into two parts. In the retrospective part, the entry and exit values of lipidograms of 21 patients with familial hypercholesterolemia and 14 patients with mixed dyslipidemia are compared. The pacients have been treated in the Center of Preventive Cardiology. The results show that total cholesterol, LDL-cholesterol and triglyceride levels are reduced after the pharmacological treatment in both groups. HDL- cholesterol remains unchanged. There are no changes in the lipidograms by patients who do not have pharmacological treatment. In the second part, the dietary habits of 8 patients, 4 with the familiarity of hypercholesterolemia and 4 with mixed dyslipidemia, are discussed qualitatively, where it is evident that nutritional education is insufficient because only two patients have visited a nutritional therapist at least once. keywords: familial hypercholesterolemia, mixed dyslipidemia, lipid metabolism, nutrition
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Searching for and Evaluating the Severity of Endothelial Dysfunction in Children with Chronic Autoimmune Disease
Sýkorová, Aneta ; Jehlička, Petr (advisor) ; Urbanová, Zuzana (referee) ; Klásková, Eva (referee)
We aimed to evaluate the endothelial function by combining RHI measurements and specific biochemical markers in the children with possible risk of premature manifestation of atherosclerosis and in the control group of healthy children. In all, 124 children (of which 106 patients divided into five groups according to diagnosis - type 1 diabetes mellitus, Crohn's disease, cystic fibrosis, familial hypercholesterolemia and acute lymphoblastic leukemia and 18 healthy controls) were enrolled in the study. During the study, we measured RHI using a new plethysmographic method and further evaluated biochemical markers of endothelial dysfunction (ADMA, E-selectin, hsCRP and VCAM) and lipidogram in individual groups of children. The primary objective of our study was the determination of RHI and biochemical parameters in healthy subjects and in selected risk groups of children (type 1 diabetes mellitus, Crohn's disease, cystic fibrosis, familial hypercholesterolemia and children after successful treatment of acute lymphoblastic leukemia). At the same time, we compared patients from individual groups with the control group. We found significantly elevated RHI values in groups of children with type 1 diabetes, Crohn's disease, cystic fibrosis, and children after successful treatment of acute lymphoblastic leukemia....
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Sequential analysis of the LDL receptor gene
MAŠKOVÁ, Denisa
Attention is currently being paid to the LDL (low density lipoprotein) receptor. It was discovered in 1985 by Goldstein and Brown who discovered its function and pathogenesis of familial hypercholesterolemia. The receptor gives a cell enough cholesterol essential to membrane synthesis and attend as a precursor to some products of cells (for example bile acids and sterols) (Ashermann et al., 2004). The mutation that affect the LDL receptor (LDLR) gene indicate some disorder of LDLR functions (Češka, 2005). The result of the disorders are increased of plasma LDL cholesterol and the associated early development of atherosclerosis and other disorders (Khan, 2014). This bachelor thesis deals with the analysis of the LDLR gene. The gene is located on the short arms of chromosome 19 in region 13.2, only exon 15 was analyzed. Identification of mutations in the LDLR gene was performed by Sanger sequencing. The sequences were processed in EditBio program and compared with the NCBI (National Center for Biotechnology Information). The methodical part was performed on a set of 15 anonymized DNA samples in which one pathological mutation (c.2253_2256dupGCTG) was found causing familial hypercholesterolemia, one probably benign (c.2225C>T), the most frequent was benign mutation (c.2232A>G) and one mutation in the intron was also found. Only one sample was without mutation.
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Laboratory markers in the process of extracorporal elimination of lipoproteins in long-term treatment of severe familial hypercholoesterolemia
CHOCHOLOUŠOVÁ, Jana
LDL-apheresis is a method of extracorporeal LDL-cholesterol elimination, which is known to decrease inflammatory processes of atherogenesis. The study is divided into two parts. THE AIM of the first part was to evaluate LDL-apheresis procedures based on immunoadsorption in 9 patients, 5 men and 4 women, (median age was 57, range 19-61 years), with severe familial hyperlipidemia (period 2004-2007). Immunoadsorption was performed by means of Cobe Spectra (COBE BCT, USA), ADA or Adasorb (Medicap, Germany) and columns of LDL-Lipopak (Pocard Ltd., Russia). Before and immediately after the procedure, blood samples were taken and serum levels of lipoproteins and some other parameters were determined. The aim of the second part was to evaluate the effectiveness of rheopheresis method and compare it with LDL-apheresis. Procedures of rheopheresis were implemented in 4 patients, 3 men and 1 woman, median age was 51 (35 {--} 67) years. During this procedure Cobe-Spectra was used; plasma was than pumped into the secondary grade filtrs Evaflux. Before and immediately after the procedure, blood samples were taken and serum levels of lipoproteins and some other parameters were determined.
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