Bulvová, L.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease I. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2017. The aim of this study was to process the summary alkaloidal extract of aerial parts of Papaver rhoeas L.; to isolate contained alkaloids using chromatographical methods; to identify them and to determine their inhibitory activity towards human enzymes acetylcholinesterase, butyrylcholinesterase and prolyloligopeptidase. Two alkaloids (+)-rhoeagenine and LB-2 were isolated, and the structure of LB-2 (its absolute configuration) is being determined nowadays. In vitro biological assays of these alkaloids found the following results: (+)-rhoeagenine (IC50 AChE ˃ 1000 μM, IC50 BuChE = 230 ± 10 μM, IC50 POP = 878 ± 45 μM) and LB-2 (IC50 AChE ˃ 1000 μM, IC50 BuChE = 314 ± 13 μM, IC50 POP = 706 ± 2 μM). The determined IC50 values of isolated alkaloids were compared with inhibitory standards of cholinesterases galanthamine (IC50 AChE = 1,71 ± 0,065 μM, IC50 BuChE = 42,30 ± 1,30 μM), huperzine A (IC50 AChE = 0,033 ± 0,001 μM, IC50 BuChE > 1000 μM, IC50 POP > 1000 μM) and rivastigmine (IC50 AChE = 0,037 ± 0,001 μM, IC50 BuChE = 0,0033 ± 0,0003...

Čakurdová, M.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimer's disease II. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2017. The aim of this work was focused on isolation of alkaloids from the fraction 1 (joined fractions 20-27), which was obtained from the summary alkaloid extract of Papaver rhoeas L. (Papaveraceae). The alkaloids were identified by structural analysis NMR, GC-MS, optical activity and melting point. Two alkaloids were identified as (-)-stylopine and (+)-rhoeadine. Isolated substances were tested on ability to inhibit the enzymes acetylcholinesterase, butyrylcholinesterase and prolyloligopeptidase. Obtained data were expressed as IC50 values: (-)-stylopine (IC50 AChE = 522 ± 67 µM, IC50 BuChE = >1000 µM, IC50 POP = >790 µM); (+)-rhoeadine (IC50 AChE = 915 ± 64 µM, IC50 BuChE = >1000 µM, IC50 POP = >790 µM). None of the isolated substances showed so potent cholinesterase inhibitory activity as the alkaloids galanthamine (IC50 AChE = 1.71± 0.065 µM, IC50 BuChE =42.30 ± 1.30 µM) and huperzine A (IC50 AChE = 0.033 ± 0.001 µM, IC50 BuChE = >1000 µM) or rivastigmine (IC50 AChE = 0.037 ± 0.001 µM, IC50 BuChE = 3.3 ± 0.3 nM)....

This thesis deals with a business project to establish a rest home for people, who are due to Alzheimer's disease fully dependent on the assistance of others. The aim is to map the current situation in the market of social services in Czech Budejovice and it's surrounding area and find out if it is possible to establish a profitable business. In the theoretical part there is a description of the conditions of the business plan and the possibility of getting a grant from EU.

Interest in hippocampus increased sharply after his significance in the process of learning and retention of information was published. In particular, considerable interest was in its volume changes and their effect on Alzheimer’s disease. Understanding the structure and function hippocampus would contribute to a more accurate diagnosis of this disease. In this work was created a method of hippocampal segmentation using active contours. With its help, the data composed of both healthy and a diseased patients was segmented and the results were then statistically analyzed using statistical methods such as Kruskal-Walis test, Mann-Whitney test. The level of significance given by results of analysis supports alternative hypothesis that attaches significance of the difference in volume of the hippocampus between studied groups.

The Huntington disease (HD) is a hereditary neuro-degenerative disorder caused by a mutation of the huntigtin gene that codes a protein of the same name. The mutated form of the huntigtin gene plays its part in many pathological interactions and influences a number of cellular mechanisms, including the immune system that could serve as a modifier of the neuropathology of the disease. The cells of the monocyte-macrophage system express cytokines whose production changes in relation to the activation of the cell. The presence of the mutated huntingtin protein in these cells renders them hyper-responsive to immunity incentives leading to changes in the production of cytokines. These differences are discernible a few years prior to the appearance of the symptoms. Therefore, the changes in the levels of certain cytokines could serve as appropriate biomarkers for monitoring of the onset of the disease and its progression. The HD pathogenesis includes an inflammation of the central neutral system. Inflammatory changes in peripheral tissues could reflect inflammatory processes in the central neural system. A miniature TgHD pig could represent an appropriate model organism for studying of the impact of the mHtt on the immune system. This model enables to observe a slow progression of the disease. Changes in...

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Kucková Supervisor: PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: Testing antioxidant properties of selected acetylcholinesterase inhibitors Very widespread Alzheimer's disease is typical by a complex pathology. Its causality is not clearly understood. There is increasing discussion due to the negative impact of free radicals on this disease formation. There are testing new substances that have also antioxidant properties, in addition to their classical effects. The aim of this diploma thesis is spectrophotometric testing of antioxidant properties of selected acetylcholinesterase inhibitors. It is based on DPPH test where the presence of antioxidants with antiradical activity causes the reduction of the color stable 2,2-diphenyl-1- picrylhydrazyl (DPPH) radical to a colorless molecule. The principle of the method is the measurement of decrease in absorbance (decolorization) of selected substances that are directly proportional to the antioxidant (antiradical) efficacy of the analyzed inhibitors. It focuses on twelve samples, Phenothiazine, which is the leader structure of new inhibitors synthesis, and two standards. Antioxidant activity is expressed as the effective...

The thesis will be devoted to individuals having a family member with Alzheimer disease. However, the mainstay will not be the disease as a whole, but caregivers and closest as themselves. The focus will be put on their memories and especially emerged relationship between caregivers, closest and caretakers. The main aim of the work is to catch the key moments having an influence to following solutions of situations and connotation, connected to dementia and as well as subsequent reflection and its own legitimation of the decision to place them into the institution unit. I would like to take into consideration the medical discourse, influencing the form of the right opinions about " properly" provided care and construction of the people with AD.

The aim of the thesis is the classification of magnetic resonance images by Deep Learning models. The goal was to predict Alzheimer's disease on the dataset created by Alzheimer's Disease Neuroimaging Initiative (ADNI). To prepare the dataset, we built two processing pipelines, which align, normalise and remove irrelevant features from brain scans. We used the processed scans for a 2D and 3D dataset. We designed a few models based on convolutional and previously proposed architectures. Although, many studies published astonishing results on ADNI classification, the results of our experiments do not support previous research in this area. Contrary to what was previously thought, we found that the accuracy strongly depends on the dataset splitting. If we split the dataset by patients, not by scans, the accuracy drops significantly. We presented an overview of several previously published architectures and our experiments showing results of these architectures on the datasets generated by random splitting or subject-based splitting. We also pointed out how the dataset splitting choice changes the performance of our models. The work is a natural extension of study [Fung et al., 2019]. 1

Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Botany (16-16130) Author: Tkáčová Beáta Supervisor: PharmDr. Kateřina Breiterová, Ph.D. Title of thesis: Alkaloids of Narcissus species cultivars and their biological activity I. Key words: Narcissus, alkaloids, biological activity, Alzheimer's disease. The main aim of this diploma thesis was to obtain summary alkaloid extracts from bulbs of five species cultivars (Narcissus cv. Acropolis, Delta, White Marvel, Kedron, Scarlet Gem) and one variety (Narcissus albus var. plenus odoratus), labeled as AL-450, AL-457, AL-460, AL-463, AL-467 and AL-508, from which samples were subsequently prepared for GC-MS analysis and screening of biological activities (cholinesterase inhibitory activity and cytotoxicity). Totally, 18 alkaloids were identified by GC-MS analysis, comparing their mass spectra. Identified alkaloids include 3-O-demethylmaritidine, 11,12-dehydroanhydrolycorine, assoanine, dehydroassoanine, galanthamine, galanthine, haemanthamine, hippeastrine, incartine, lycoramine, lycorine, narwedine, norpluvine, pancracine, pluvine, pseudolycorine and tazettine. Samples of cultivars AL-457, AL-460, AL-463 and AL-508, showed relatively promising hAChE inhibitory activity in screening assay (c = 50 µg/ml),...

This This thesis concentrates on the issues faced by family carers, who take care of their family members diagnosed with the Alzheimer's disease. Special education also relates to seniors and its principles can therefore be used in this age group. The goal of this thesis is to discover and describe challenges faced by the family carers while they support their family members with Alzheimer's. The thesis focuses on the Alzheimer's disease itself, its causes and risk factors. The thesis also concentrates on the origins of the disease, its stages, diagnostics and therapy. Next, psychic and physical burdens of the family carers are depicted. The thesis also introduces organizations that specialize in providing informal support for the family carers and relief care, and disease related legislation is listed. The necessary research data were collected through semi-structured interviews with direct family carers. KEYWORDS Alzheimerś disease, caregiver, home care, family member, dementia