Animal models of Alzheimer's disease display cognitive insufficiencies which mimic human symptoms and occur at a given age or post-treatment time. Animals are typically tested using canonical behavioral tests, lasting minutes and taking place mostly in the non-active period of the daily cycle. Animals are exposed to certain amounts of manipulation-induced stress. Our work represents a validation study for the rat behavioral system IntelliCage. The tested individuals live freely in a group and their behavior is monitored continuously. It is however possible to set up individual tests for each animal or a group of animals. The rats are not subject to human manipulation and hence the results are not affected by manipulation-induced stress. We tested early cognitive impairment in the transgenic rat model TgF344-AD at 6 - 8 months of age. Further, we tested two most common protocols of the streptozotocin model, i.e. single dose of intracerebroventricular 3 mg/kg streptozotocin and double dose 48 hrs apart. Results were compared with the canonical Morris Water Maze (MWM) test. In the MWM test, transgenic animals did not differ from controls in any of the studied parameters. The streptozotocin model displayed a deficit only in the double dose group. However in the IntelliCage, transgenic animals displayed...

THE ABSTRACT The thesis deals with sibling relationships of twins and triplets when one or more siblings suffer from some health disability or handicap. It outlines the way of life in sibling constellations of twins and triplets. It deals with the topic of a disabled person who has brothers or sisters. It defines family as a pillar of person's life and it focuses on the sibling relationships. The thesis explains the connection between multiple births and the occurrence of disability, and it considers certain aspects of family life, with the main focus on siblings, when one of the siblings suffers from some health limitation. It also describes twins and triplets and their specific features. For example, it shows the development of the identity of each of the siblings, the role of their birth order, the types of relationships that occur in a family with twins and triplets, and the way the siblings may experience the separation from one another. It draws on publications and other sources that deal with sibling constellations and the resulting relationships among the siblings, on the publications on twins and triplets, on children and adults with disability or handicap. Last not least, it draws on personal experience of the author and on the research interviews. Apart from that, the thesis clarifies how twins...

Thesis entitled "The issue of institutional care for the elderly with Alzheimer's disease" includes information about different types of dementia, charts the current situation in the Czech Republic and in the world, characterized fundamental questions of social policy and presents some methods of non-pharmacological treatment. The research analyzes the conditions of life of seniors with Alzheimer's disease who live in different types of institutions. It also focuses on family members. For compact view on the topic contribute opinions of experts from relevant institutions. Aim of this study is to describe and compare the system of care in individual and institutional facilities using statistical information to point to the timeliness issue.

Niemann-Pick disease type C (NPC) is a rare, severe disease with autosomal recessive inheritance. Disease is caused by pathogenic mutations located in genes NPC1/NPC2. These genes encode lysosomal non enzymatic NPC1/NPC2 proteins that are part of lipid transport. As a result of malfunction of these proteins intracellular accumulation of lipids occurs, in particular free cholesterol and glycolipids. Causal therapy is currently still unsatisfactory therefore new therapies are evolved. However these therapies depend on whether the patient cells contain at least residual amount of transcript NPC1 gene. In a group of patiens, for which a fibroblast culture was available, I analyzed the effect of pathogenic mutations on the expression level of the transcript. Results showed that for all pathogenic mutations transcript level is low, but detectable. Moreover, I characterized the structure of the NPC1 gene promoter. By sequence analysis I found polymorphisms rs8099071, rs28403610, rs2981422, rs1652354, rs1788774, rs1788772 in promoter. On the basis of the composition of polymorphisms in individual patiens, I estimate six different haplotypes. I performed mutation analysis in DNA of recently diagnosed patient. I found only one pathogenic mutation p.I1061T (c.3182T> C) in the NPC1 gene. Therefore I tested...

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....

In comparison to men, the number of X-linked genes is doubled in women as they have two chromosomes X while men are hemizygotes for X-linked genes. This imbalance is compensated by X inactivation (XCI) process, also known as primary X-inactivation, occurring in the early stage of embryogenesis. X inactivation is a random process and females are mosaics of two cell populations. The ratio of expressed alleles in women can be random (50:50) or skewed (≥80:20). The skewed X inactivation may occur due to selection when one of the alleles is preferentially inactivated (secondary X inactivation). In this study XCI status in heterozygous females with various severity of phenotypic symptoms and traits in selected X linked inherited metabolic diseases is analysed, with the focus being Fabry disease - the deficiency of the enzyme alpha-galactosidase A encoded by GLA gene. Moreover, XCI in one family with X linked agammaglobulinemia is examined. Mutant alleles and XCI status based on various loci, different methodical approaches and different tissues is subjected to examination. For the first time, the direct analysis of GLA gene transcript to detect the allele ratio was used alongside with the single-nucleotide polymorphisms in the IDS and LAMP genes for allele-specific expression (ASE) and the AR, RP2 and...

Human autopsy or biopsy tissue samples, mouse models and cell cultures of various types represent the most common materials in the investigation of cell pathogenesis of inherited diseases. This dissertation is devoted to all these approaches in the study of two X-linked lysosomal storage diseases, Fabry disease (FD,α-galactosidase A (AGAL) deficiency) and mucopolysaccharidosis type II (MPSII, idunorate-2- sulfatase (IDS) deficiency). The primary goal of the work was analysis of lipid blood group B antigens with terminal α-galactose (B-GSL) in the pancreas of FD patients with blood group B (FD-B).,In addition to the main glycosphingolipid (GSL) substrate, globotriaosylceramide (Gb3Cer), B-GSLs represent another minor substrate of AGAL. The deposition of undegraded B-GSL has been demonstrated in FD-B pancreas where it was significantly higher than in other organs such as the kidneys and lungs which accumulate mainly Gb3Cer. High concentration of lipid and non-lipid B-antigens was primarily confirmed in exocrine acinar epithelial cells of FD-B, accompanied by massive accumulation of ceroid (secondary sign of lysosomal storage). Unlike acini, the endocrine portion of the pancreas remained unaffected by accumulation of AGAL substrates. This interesting phenomenon of cell biology shows how a specific...

The aim of this diploma thesis is to identify options of how to use the systém of coordinated rehabilitation in a home with a special regime. To obtain information I used qualitative research methodology. Semi-standardized interviews served as the research tool. These interviews were carried out with 10 employees of a home with a special regime run by the City Institute of Social Services in Strakonice. The thesis is divided into a theoretical and a practical part. The theoretical part of the diploma thesis focuses on coordinated rehabilitation as a whole, further, it discusses the individual parts of coordinated rehabilitation. Other chapters describe the most frequent client diagnoses within the Home with a special regime, and finally the standards of social service quality are mentioned. The main research question: What are the options of using coordinated rehabilitation in a home with a special regime? Partial research question: Are employees informed about the options of coordinated rehabilitation? For the purposes of the interview I used questions focused on general identification data, questions focusing on the importance of coordinated rehabilitation, multidisciplinary team. Further, I asked about the individual components of coordinated rehabilitation, and finally, how individual planning is carried out. The result of this diploma thesis is a finding that individual components of coordinated rehabilitation are not fully mutually connected. It would be useful to provide employees with suitable courses to complete their missing knowledge. This diploma thesis might serve as a tool for improving care in the Home with a special regime, it might contribute to the Home with a special regime´s employer awareness of coordnated rehabilitiation, and connect it with practice.

Wilson's disease is a hereditary disorder of copper metabolism, which causes copper accumulation in organism, especially in the liver, kidneys and brain. Current treatment is based on using low-molecular weight copper chelators and high doses of zinc salts. Unfortunately, they can induce some severe side effects due to systemic action. The aim of this thesis is to improve the treatment of Wilson's disease by using of polymeric drug delivery systems. The size of polymer particles in tens of microns should provide non-resorbability of the drug after oral administration. Synthetic microparticles of poly(glycidyl methacrylate-co- ethylene dimethacrylate), natural microcrystalline cellulose and cross-linked chitosan were used as polymer matrices. N,N-di(2-pyridylmethyl)amine, triethylenetetraamine and 8-hydroxyquinoline were selected as specific copper chelators, which can complex copper cations with high efficiency. The principle of the proposed treatment is that the polymeric carrier-bound chelator complex copper directly from the food in digestive tract of the organism. Because of non-resorbability, the entire complex should be eliminated from the body together with stools. This virtually eliminates systemic side effects. The ability of adsorption of copper and the stability of polymer complex under...

Pathogenesis of mucopolysaccharidosis type IIIC (MPS IIIC) and Gaucher disease has not been yet fully clarified, and the causes of phenotypical variability between the patients with the same genotype in Gaucher disease remain obscure. Because the variants in the regulatory regions of genes can cause phenotypical differences mentioned above, I have studied promoter regions of HGSNAT and GBA genes mutated in these lysosomal disorders. I have shown that there is an alternative promoter of GBA (P2). Additional studies were aimed to elucidate possible physiological functions of P2, and its possible role in the pathogenesis of Gaucher disease. I have found that P2 is not tissue specific, and that its variants do not influence the variability of phenotype in Gaucher patients with the same genotype. P2 is used differentially neither during the differentiation of monocytes to macrophages nor in macrophages from controls and Gaucher patients, in whom there is a prominent storage only in cells of macrophage origin. We have thus not found any changes that would suggest a role for P2 in the pathogenesis of Gaucher disease. I have characterized the promoter region of HGSNAT and shown that the binding of Sp1 transcription factor is important for its expression. Sequence variants found in HGSNAT promoter in...