Pavuková, S.:Vinca minor L. alkaloids and their biological activity II. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové 2020. Vinca minor L. is a species of species of flowering plant, native mainly to central and southern Europe, which containst more than 50 indole alkaloids. During screening of potential plant inhibitors against human acetylcholinesterase (hAChE) and butyrylcholinesterase (HBChE) at our department, an alkaloidal extract from dried aerial parts of Vinca minor demonstrated strong and selective hBChE inhibitory activity with an IC50 value of 13.60 ± 0.83 μg/mL, however, against hAChE was inactive (IC50 value >100 μg/mL). The fraction VM 323 - 327 (4,72 g) was separated by column chromatography on silica gel again with stepwise elution by using chloroform and ethanol and overall 7 joined fractions were obtained.Subsequently, repeated preparative TLC on silica gel led to isolation of three compounds; the newly isolated substance SP-1, (-)-picrinine (SP-2) and deacetylakuammiline (SP-3). Their structures were elucidated with mass spectrometry (ESI), NMR and optical rotation. Isolated alkaloids were tested on ability to inhibit AChE, BuChE, POP a GSK-3β, which are enzymes playing an important role in...

Thesis named Calculation of advanced diffusion parameters in brain grey matter from DKI MRI images deals with processing of diffusion-weighted images from DKI. The thesis contains review of literature on principle of diffusion, influence of diffusion on MRI, calculation of DTI and DKI parameters and clinical application of diffusion-weighted maps with focus on grey matter. The thesis focuses on software tools for processing and pre-processing DTI and DKI. The practical part consisted of two sections. Two different softwares were used to calculate maps of diffusion parameters. Diffusion parameters from anatomical structure sunstantia nigra were compared between group of healthy controls and patients with Parkinson’s disease. This comparison did not show any statisticaly significant difference. In the second step, a script for creating diffusion maps in software Diffusinal Kurtosis Estimator was made.

The causative role of the huntingtin (HTT) gene in Huntington's disease (HD) has been identified more than 25 years ago. The extension of CAG repeat stretch over 39 repeats in exon 1 of one HTT allele results in full penetrance of this neurodegenerative disorder. While the identification of the causative mutation raised hopes that development of the therapeutic compound will be easily achievable, the patients and their families are still waiting for treatment until now. The main reason for that might be the complex cellular function HTT that makes the determination of the pathologic mechanism difficult and the development of treatments even more challenging. Although a lot of different animal models have been generated until now, establishing a suitable model has still not been achieved yet. Due to its anatomy, physiology, and genetics, the minipig seems to be a suitable candidate for neurodegenerative disease models. Indeed, the existing Transgenic (Tg) Libechov minipig model manifests signs typical for HD in patients, but on the other hand significant inconsistencies have also been observed. The finding of malformation that partially shows the situation in human patients is true for both, the male reproductive tract as well as for the brain. The reason for this might be the fact the genetic...

Hĺbková mozgová stimulácia (DBS) predstavuje účinnú liečbu pre pacientov s Parkinsonovou chorobou (PD) alebo farmakorezistentnou epilepsiou. Avšak mechanizmy, ktorými znižuje počet záchvatov a zlepšuje pohyb, zostávajú ešte do značnej miery neznáme. Pre lepšie pochopenie a určenie, v ktorých frekvenčných pásmach je zmena najdôležitejšia, boli urobené porovnania medzi vypnutou a zapnutou DBS pomocou korelačnej metódy a indexu fázového posunu. Jedenásť pacientov s PD a naimplantovanými neurostimulátormi z firiem Medtronic a St.Jude Medical bolo predmetom nahraných dát použitých v tejto práci. Výsledky dokazujú, že zmena konektivity počas DBS nastane a zároveň, že najviac ovplyvňuje najvyššie frekvencie ako beta, nízka gama a vysoká gama. Zmeny v týchto frekvenciách, zodpovedné za motorickú aktivitu, sústredenie a spracovanie informácií, sú v súlade s klinickou teóriou o PD. Počas tejto choroby je patologická beta aktivita hypersynchronizovaná a gama aktivita je znížená práve v motorických oblastiach. Ak sa gama aktivita počas zapnutej stimulácie zvyšuje, fyziologický stav pacientov sa čiastočne znovuobnovuje a tým zlepšuje ich hybnosť. Metódy a výsledky tejto práce budú použité pre ďalší výskum pacientov s PD a epilepsiou.

Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused by an unstable expansion of the CAG repeat sequence within the huntingtin gene. Huntingtin associates with ubiquitin-proteasome system that ensures degradation of particular proteins including β-catenin which is an important molecule whose equilibrated degradation is necessary for the proper functioning of the Wnt signaling pathway. The binding of β-catenin to the destruction complex is altered in HD, leading to the toxic stabilization of β-catenin. The main goal of my thesis was to determine whether the accumulation of β-catenin due to the presence of mutant huntingtin is also characteristic of Liběchov minipigs, a large animal model of Huntington's disease stably expressing N-truncated human mutant huntingtin. Using immunoblot and specific antibodies, we have revealed age-dependent accumulation of mutant huntingtin in transgenic minipigs. Unlike endogenous huntingtin, no decrease of the level of mutant huntingtin was observed in the striatum of transgenic animals. Surprisingly, this was followed by a decrease of phosphorylated β-catenin. Nevertheless, our results demostrate the accumulation of β-catenin in mesenchymal stem cells isolated from the oldest boars during ontogenesis. Furthermore, we have revealed a...

The aim of this thesis is to map regional variability in the intensity of mortality using methods avoidable mortality and a few selected characteristics of health care. The thesis describes the development of the concept of avoidable mortality, which is then used for the Czech Republic for the period 2006-2010 and to individual districts for the period 2006-2010. Furthermore, this thesis focuses on the relationship between expenditures of General Health Insurance Company and the level of mortality in the regions. For showing regional differences depending on the health care intensity of mortality from ischemic heart disease (both acute and chronic forms) was also selected, depending on the distance of specialized medical care. The last chapter focuses on National screening programs and cancer mortality, which are integrated in a comparison of the percentage of people examine in this program for districts. The relationship between spending per insured and intensity of mortality and outcomes related to the intensity of mortality, depending on the availability of specialized health care has been confirmed by statistical methods - correlation (Pearson correlation coefficient). Relationship between the intensity of mortality in cancer within screening programs and the percentage of people who passed...

Huntington's disease (HD) is an autosomal dominant hereditary neurodegenerative disease characterized by motor, cognitive and behavioral disorders. HD is caused by expansion of CAG triplet (cytosine-adenosine-guanine) located in a gene on the short arm of the fourth chromosome. This expansion encodes an aberrant polyglutamine chain in the protein huntingtin. Physiological and mutated huntingtin (in case of HD) are expressed in almost all tissues and influences many cellular functions. The prevalence of HD in population is about 1 per 10.000. The disease is currently incurable and its mechanisms are not sufficiently understood. Besides affecting the central nervous system HD also affects peripheral tissues, including skeletal muscles. HD disrupts mitochondrial function and damages oxidative phosphorylation system, which has the task of producing energy in the form of ATP in cells. Research of transgenic minipig model for HD could help elucidate the mechanisms of disease's pathogenesis and potential therapeutic strategy. In this diploma thesis, immunodetection with help of specific antibodies to detect changes in amount of 14 selected mitochondrial proteins in skeletal muscle tissue of three age groups of transgenic HD minipigs - 24, 36 and 48 months old was used. Gradual progression in reduced...

Obesity is very widespread and detrimental to health. Obesity brings with it many changes including heightened immune function, and a higher prevalence of major cardiovascular disorders, cancer, diabetes, and Alzheimer disease. Obesity is also associated with shortened lifespan. The detrimental effects of obesity are linked to the "metabolic syndrome", a broad range of changes in metabolic processes and immune function. As a first approximation, we agree with this formulation but we will then proceed to document some of its weaknesses. (i) Crude mortality rates increase with increasing body mass index (BMI) but as the BMI approaches the normal range, mortality rates reverse (the now classic "J-shaped curve") so that individuals with reduced BMI have elevated mortality. (ii) A multiplicity of medical and surgical conditions have been reported where short term and medium term outcomes are better for overweight patients. These conditions are placed under the heading of "obesity paradox". (iii) The medical community has introduced a binary system for the metabolic syndrome ---- yes, patient has it or no, the patient does not have it, despite the fact that all of the changes that are considered components of the metabolic syndrome are continuous variables. Our work is focused on sharpening focus and improving...

Univerzita Karlova 1. lékařská fakulta Studijní program: Doktorské studium biomedicíny 1. LF UK Studijní obor: Oborová rada Fyziologie a patofyziologie člověka MUDr. Gabriela Dostálová Disertační práce Vybrané aspekty akutního infarktu myokardu u mladých nemocných Specifics of Acute Myocardial Infarction in Young Adults Školitelé: prof. MUDr. A. Linhart, DrSc., doc. MUDr. D. Karetová, CSc. Praha 2017 Abstract Coronary heart disease is the leading cause of death in adults in the western world. Myocardial infarction can represent the lethal manifestation of coronary heart disease leading to sudden cardiac death. Although myocardial infarction mainly occurs in patients older than 45 years, the young population can be affected as well. Despite the relatively low incidence of myocardial infarction in the young population, the mortality rates and long-term disability make acute myocardial infarction in young patients an important clinical issue. Consequences of myocardial infraction usually have great impact on the young patient's psychology, ability to work and the overall quality of life. The management of young myocardial infarction patients should differ at least slightly from the older ones. Young patients usually have a different risk factor profile, clinical presentation, and prognosis in comparison with...

Alzheimer disease (AD) is the most frequent dementia. The prevalence is approximately 10% in 65 years old people. The current treatment is only progression protective, therefore it is crucial to find a new diagnostic approach for diagnosing AD in early stage. We analysed a set of 55 patients by the drop coating deposition Raman spectroscopy with the goal to verify previously published high sensitivity of the AD spectroscopic diagnosis in cerebral spinal fluid (CSF) and to find a new diagnostic method for blood serum (BS). We optimized measurement conditions for BS. The results were evaluated by the cluster analysis and the principal component analysis. The small set of samples exhibited high sensitivity in both CSF and BS but that distinctly decreased in the whole set. The results for CSF were affected by the choice of the analysed spectral interval. The best for AD diagnose was the interval containing peaks at 980, 1080 and 1249 cm-1.The results for BS have been the most sensitive in the whole spectral range. They have low sensitivity but high specificity for AD (92%). The usage of neural networks has conversely high sensitivity and low specificity in both sets of samples of BS and CSF. Powered by TCPDF (www.tcpdf.org)