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Effect of amyloid β on the function of endosomes and lysosomes
Tmějová, Monika ; Rudajev, Vladimír (advisor) ; Búran, Peter (referee)
Amyloid β peptide is produced by proteolytic processing of amyloid precursor protein. Accumulation of toxic Aβ in lysosomes and endosomes is considered to be one of the earliest signs of Alzheimer disease. Alzherimer disease was first described in 1907 by doctor Alois Alzheimer. This disease is most common in elderly people over the age of 65 and it is currently the most common cause of dementia. Although significant progress has been made in recent years, the key mechanism of formation of senile plaques and neurofibrillary tangles still remains unclear. Vesicular trafficking plays fundamental role in regulation of APP and generation of Aβ. This thesis summarizes molecular mechanisms of pathological effect of Aβ on the endolysosomal complex.
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The importance of lipid composition of membranes for the development of Alzheimer's disease
Novotná, Natálie ; Rudajev, Vladimír (advisor) ; Hanousková, Barbora (referee)
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.
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Signs of epilepsy spectrum disorder in persons with psychostimulant addiction
Jakubová, Žaneta ; Herink, Josef (advisor) ; Kudláčková, Zděnka (referee)
Bc. Žaneta Jakubová, Specialist in laboratory methods Signs of epilepsy spectrum disorder in persons with psychostimulants addiction Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences, Background: The aim of this diploma thesis is to study the occurrence of symptoms of epileptic spectrum disorder in psychostimulant subjects and to demonstrate the effect of psychostimulants on the occurrence of this disorder. Methods: For questionnaire survey was used to collect the data, in which probands submitted a total of 3 questionnaires. Input anamnestic questionnaire to obtain general information, the remaining two are focused on symptoms of epileptic spectrum disorder - Complex Partial Seizure-like Symptoms Inventory (CPSI) and Limbic System Checklist-33 (LSCL-33). Statistical methods of percentage comparison, chi-square test and unpaired t-test were used for evaluation. Results: Unusual scores and scores for epileptic spectrum disorder reached a total of 60 % of respondents in the CPSI. In the LSCL-33 questionnaire, a suspect and abnormal score reached 100 % of respondents. Conclusions: Both hypotheses have been demonstrated, namely that psychostimulants influence the occurrence of symptoms of epileptic spectrum disorder and that...
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The role of glia in neuroprotection
Fider, Jan ; Novotný, Jiří (advisor) ; Telenský, Petr (referee)
Verterbate brain is extremely demanding on energy and oxygen consumption. A few seconds of the oxygen deprivation can disrupt brain homeostasis and cause an ionic imbalance, resulting in neuronal death by apoptosis or necrosis. The mechanisms, that are responsible for protection of the CNS against the disruption of homeostasis are called neuroprotection. Neuroprotection in the brain is mostly provided by glial cells. There are several types of glia in the human brain, but not all of them are responsible for neuroprotection equally. However, in general we can say that all the glial cells are responsible for the maintainance of ionic balance, which play an important role in neuroprotection. Astroglia and mikroglia dominantly contribute to protectiion of the CNS. These cells can be activated by any disruption of the CNS and actively execute a number of neuroprotective actions. Activated astrocytes form astrogliosis, which covers and separates the affected area of the brain from healthy tissue, thereby preventing further spread of ischemic damage. Activated microglia can transform into phagocytes which clean the extracellular space from dead cells and their parts. Neuroprotection research is nowadays very popular. This is because of urgent need better understanding of the causes of neurodegenerative...
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Lead and its Effects on Health under the REACH
Krajíčková, Michaela ; Bendl, Jiří (advisor) ; Mihaljevič, Martin (referee)
With decreasing use of leaded petrol and the subsequent creation of further restrictions of lead exposure in an urban environment plummeted. Because lead is still available in several types of articles, the reduction of lead in our environment has come to a halt before reaching sufficiently low levels. New EU regulation REACH introduces new rules for the marketing of substances, mixtures and articles on the market. In September 2012, ordered by the European Commission under the REACH proposal banning the use of lead and its compounds in jewelery. It is now proposed to limit lead in products, such as shoes, clothes, accessories, interior decoration, pens and keys. The objective of the thesis is to inform about the presence of lead in consumer commodities and its dangers. Lead and its compounds are highly toxic and can cause lots of health issues. Especially its neurotoxical effects can affect the development of children nervous system, so it is essential to lower the occurence of lead in products on the market. Powered by TCPDF (www.tcpdf.org)
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The effect of pyrethroid based pesticides on fish
RICHTEROVÁ, Zuzana
Pyrethroids are ones of the most used pesticides worldwides. The widespread use and high stability of pyrethroids lead to the assumption of that their occurrence in the environment could be quite frequent. They can reach water ecosystem as pollutants. Residues of pyrethroids are not only detected in the water column, but also in sediments and in fish tissues. The first study was devoted to the product Nexide containing 60 g.l-1 of active substance gamma-cyhalothrin. Tested Nexide concentrations were 5, 25, 50, 100, and 250 µg.l-1. Early life stage test was used.Common carp (Cyprinus carpio) was tested. There were significant mortalities in all concentrations except the lowest concentration during the trial. The lowest concentration tested 5 µg.l-1 only caused a slightly increased mortality. This lowest concentration influenced the growth in length and weight negatively, decelerated ontogenetic development, and made the body surface of the individuals darker. Histopathology of individuals from this concentration revealed dystrophy in liver. Examination of kidney, intestine and gills did not show significant histopathological differences compared with control. The evaluation of selected parameters of oxidative stress demonstrated a significantly higher activity of detoxification enzyme glutathione-S.transferase (GST) and a significantly lower activity of defensive enzyme glutathione peroxidase (GPx) compared with the control group. The other examined parameters of oxidative stress such as catalase (CAT), glutation reductase (GR), and lipid peroxidation determined by using the thiobarbituric acid-reactive substances (TBARs) were comparable to the control group. Changes in oxidative stress parameters suggest that exposure of the organism to the product Nexide in the given concentration leads to dysbalance of defensive enzymes. The second study was devoted to the product Cyperkill 25 EC containing 250 g.l-1. Tested Cyperkill 25 EC concentrations were 7.2, 36, 72, 144, and 360 µg.l-1. The procedure of the trial was the same as the preceded one. There were 100% mortalities in all concentrations except the lowest concentration during the trial. The lowest tested concentration 7.2 µg.l-1 allowed 90% of individuals to stay alive till the end of experiment. The lowest concentration influenced the growth in length and weight negatively and decelerated ontogenetic development compared with the control. Any individual exposed to this concentration did not reach juvenile stage until the end of the trial. Dark pigmentation was visible in 68% of these exposed individuals on the last day. Similar darkening was visible in individuals from higher concentrations shortly before death too. Histological examination did not revealed significant changes in intestine, liver, kidney, and gills compared with the control group. Evaluation of selected parameters of oxidative stress demonstrated significantly lower activities of GST, GR, and GPx. Activities of CAT and TBARS were comparable with the control group. Changes in oxidative stress parameters suggest that exposure of the organism to the product Cyperkill 25 EC in the given concentration could induce oxidative stress and interfere with the activities of antioxidant enzymes. The presented thesis summarises actual data about pyrethroids and their influence on fish. The demonstrated effects confirm high susceptibility of early developmental stages of fish to tested pesticides. When interpreting the results, we have to take into account the fact that studies showed this risk even on single pyrethroid substances. But water organisms are exposed to many other more or less toxic products and substances in a real environment. These xenobiotics could react with each other and their mixture could even potentiate negative effects. The performed studies also clearly show the significant differences in the sensitivity of embryonic and embryolarval tests.
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