Search

This diploma thesis concerns the most used drug, alcohol. The theoretical part consists of chapters concerning alcohol characteristics, pharmacology effects of alcohol consumption on the human body, and alcohol consumption by youths. Moreover, the thesis defines addiction and focuses on drug issues and their prevention. This diploma thesis mainly aims to reveal the knowledge of alcohol effects and consequent risks of high school students in all years based on the number of correct answers. The minor aims are to find the comprehension of given students in alcohol law, the first experience with alcoholic beverages, the frequency of alcohol consumption in the previous 30 days, and the way of alcoholic beverages providing. The aims have been assessed based on a questionnaire focused on alcohol knowledge and alcohol consumption. According to the questionnaire findings, the students appear to have a decent knowledge of alcohol's effect on the human body and the consequent risks of alcohol consumption. Also, most of them have already had an experience with alcohol. Furthermore, the practical part incorporates an interactive lecture proposal focusing on alcohol and its consequence on the human body. The lecture aims at students in high school's first and second years. KEYWORDS alcohol, dependence,...

The objective of this bachelor thesis was to provide a comprehensive review of published data on the toxicity and mechanism of action of cyanides in fish and on emergency conditions caused by cyanide spills into the aquatic environment. Cyanides are present in simple form such as CN- and HCN. They also occur in complexes and organic forms. Cyanides form complexes with metals. The cyanocomplexes of cadmium and zinc are the most toxic. Conversely, cyanocomplexes with gold are the least toxic. The organic forms include nitriles, cyanogenic glycosides and cyanohydrins. Sources of cyanides are natural and anthropogenic. Anthropogenic sources are the most important sources of cyanide. The main producers of cyanide pollution and frequent sources of cyanide spills into the aquatic environment include industries involved in the extraction, treatment, and processing of metals. Information about the toxicity of different forms of cyanide to different fish species under various environmental conditions is collected and clearly presented in this bachelor thesis. When comparing the toxicity of simple and complex cyanides to the same fish species under the same environmental conditions, it is evident that, with few exceptions, the LC50 values are lower for simple than for complex cyanides. Temperature has a significant effect on the toxicity of cyanides. Cyanide toxicity decreases with increasing temperature for most fish species. Different sensitivities to cyanide have been observed in different life stages of fish. Embryos and larvae appeared to be the most resistant. In opposite, juveniles and adults were the most sensitive to cyanide. In my bachelor thesis I also made a review of published information on accidental fish kills caused by the release of cyanide into the aquatic environment in the Czech Republic and some of the world's major cyanide accidents. The source of contamination of the aquatic environment was mostly industrial wastewater from metal processing and treatment or from cyanide production in the Czech Republic. Cyanide spills have been recorded, particularly in connection with gold and silver mining in the world. The main causes of cyanide spills into the aquatic environment were the collapse of a control or safety device in detoxification tanks and tailings ponds containing cyanide wastewater. In many cases, staff failed to detect the malfunction in time.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Karolína Skoupilová Supervisor: prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Are currently used chelators of heavy metals also chelators of calcium and magnesium? Calcium and magnesium are important elements for the human body. Calcium plays an important role in blood clotting and intracellular signalling, thus participating in muscle contraction and platelet aggregation, among other processes. Magnesium is a cofactor for many enzymes. A significant deficiency of both ions can manifest as disorders of heart rhythm and increased neuromuscular excitability. The aim of this study was to determine the chelating activity of currently used heavy metal chelators and to determine the stability of the indicator. First, the ideal pH for the experiment was determined. In the next step, the chelation rate of 21 known metal chelators was measured using an in vitro spectrophotometric method. Finally, the chelation of the most active calcium chelators was verified on platelet aggregation in a human blood sample. At the same time, the long-term stability of the indicator o- cresolphthalein complexone (CC) was determined. In the first step, pH 7.5 was chosen, which was the only one...

Studium exprese a toxicity derivátů katecholu v prsních nádorových buněčných liniích, Tereza Vyoralová ABSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Tereza Vyoralová Supervisor: PharmDr. Alejandro Carazo Ph.D. Title of the diploma thesis: Study of the expression and toxicity of catechol derivates in breast cancer cell lines Estrogens have several important functions in the human organism and are also involved in the formation and development of breast cancer. These effects are mediated by binding to estrogen receptors (ER) and show complex spectrum of effects such as regulation of reproduction, menstrual cycle, brain function, bone density or mobilization of cholesterol. In addition the presence and quantification of ER in breast cancer is currently used as one of the most important predictive biomarkers in patients suffering from this disease. The occurence and activity of ER correlates with the response of breast cancer to hormonal treatment and with the patient's prognosis. Despite intensive research, breast cancer is still ranked among the cancers with the highest lethality. Catechols are organic compounds that are naturally present in food as pollutants, but also can be found in the human body, where they play an important role as...

Microplastics are tiny particles smaller than 5 mm in size found in various environments, including seas, rivers and soil. These particles can be intentionally produced as part of cosmetic products or formed by the breakdown of larger plastic objects. Microplastics represent a serious threat to the environment and animals and could eventually reach humans through the food chain. This thesis deals with a critical and synthetic overview of the literature related to the influence of microplastics on the metabolism of animal cells. The thesis also considers the experimental conditions under which the data were obtained. In particular, factors such as the tested microplastics' shape, size and ageing are critically evaluated as these aspects are often neglected in the literature. Current knowledge shows that microplastics accumulate in the bodies of animals and cause physical and metabolic damage, inflammation, disruption of energy metabolism, protein metabolism and amino acid and lipid metabolism. The most serious effects of microplastics can be considered to be the formation of oxygen radicals, neurotoxicity, disruption of gametogenesis and offspring development.

Disinfection of swimming pool water is necessary for reducing the risk of disease transmission. Disinfection by-products form when chlorine reacts with organic matter contained in water. More than six hundred disinfection by-products have been found in swimming pools. Trihalomethanes, haloacetic acids, chloramines, halonitromethanes, haloacetonitriles and nitrosamines are among the most frequently occurring. Disinfection by-products may be toxic. The volatility of some of them causes their occurrence in the surrounding air and poses a risk not only for swimmers, but also for people in the vicinity who are not in direct contact with the water. DBPs enter human body by inhalation, absorption through the skin and ingestion. They have been linked to health problems such as skin and eye irritation, bladder cancer and respiratory diseases. Preventing their occurrence is not an easy task; a number of factors play a role in their genesis (the amount of organic matter, type and the amount of disinfection, the quality of source water, temperature, pH) and not all principles of their formation have been fully clarified yet. Further research on DBPs and their sufficient regulation are important steps to maintain chemical safety in swimming pools. Key words: disinfection by-products, swimming pool,...

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Jana Elbelová Supervisor: PharmDr. Alejandro Carazo, Ph.D. Title of the diploma thesis: Study of the influence of natural drugs on estrogen receptor and confirmation of their influence in cell culture Estrogens are one of the main reproductive hormones in women. Their function in the human organism is mediated by the estrogen receptor (ER). Estrogens are involved in important physiological processes such as reproduction, bone metabolism and cardiovascular function. Long term elevated levels of these hormones may also lead to breast cancer development. Phytoestrogens are natural ligands of estrogen receptor widely found in dietary products. These compounds have beneficial properties in treatment of menopausal symptoms thank to their estrogenic activities but are able to function as antiestrogenic agents too. In addition, they may play a role in the development of other illnesses (breast cancer etc.). Therefore, they can be considered as a potential pharmacological tool for the treatment of estrogen-related conditions. Within this master thesis, a total of six compounds, two phytoestrogens and four of their more relevant metabolites, were chosen (genistein, daidzein, S equol, O...

Vitamin D has essential role in skeletal health, however studies over the recent years have outlined its implication in many other physiological functions. The importance of vitamin D for health has, on one hand, raised needs for supplementation but may, on the other hand, lead to excessive administration. Vitamin D toxicity or hypervitaminosis D due to excess of vitamin D is a medical condition manifested mainly as hypercalcemia, with mostly gastrointestinal and neuropsychiatric symptoms. Long-term administration of large doses of vitamin D can result in vascular calcification and hence by associated with a cardiovascular risk. Hypervitaminosis D is extremely rare likely due to high therapeutic index of vitamin D. The clinical research shows an administration of 10.000 IU/day of vitamin D, which meets the criteria for the tolerable upper intake level, even for extended period, is probably not associated with adverse effects in almost all individuals in general population. However there are case studies globally showing vitamin D toxicity can occur due to misuse of over-the-counter vitamin D supplements, inappropriate prescribing or uncontrolled administration of high dose unlicensed preparations.

At present, nuclear condensation and fragmentation have been estimated also using Hoechst probes in fluorescence microscopy and flow cytometry. However, none of the methods used the Hoechst probes for quantitative spectrofluorometric assessment. Therefore, the aim of the present study was to develop a spectrofluorometric assay for detection of nuclear condensation and fragmentation in the intact cells. We used human hepatoma HepG2 and renal HK-2 cells cultured in 96-well plates treated with potent apoptotic inducers (i.e. cisplatin, staurosporine, camptothecin) for 6-48 h. Afterwards, the cells were incubated with Hoechst 33258 (2 mu g/mL) and the increase of fluorescence after binding of the dye to DNA was measured. The developed spectrofluorometric assay was capable to detect nuclear changes caused by all tested apoptotic inducers. Then, we compared the outcomes of the spectrofluorometric assay with other methods detecting cell impairment and apoptosis (i.e. WST-1 and glutathione tests, TUNEL, DNA ladder, caspase activity, PARP-1 and JNKs expressions). We found that our developed spectrofluorometric assay provided results of the same sensitivity as the TUNEL assay but with the advantages of being fast processing, low-cost and a high throughput. Because nuclear condensation and fragmentation can be typical markers of cell death, especially in apoptosis, we suppose that the spectrofluorometric assay could become a routinely used method for characterizing cell death processes. V současné době se k detekci jaderné kondenzace a fragmentace využívají fluorescenční sondy Hoechst. Žádná z metod však nepoužívá sondy Hoechst pro kvantitativní spektrofluorometrické hodnocení. Cílem této studie bylo vyvinout spektrofluorometrický test pro detekci jaderné kondenzace a fragmentace v intaktních buňkách. Použili jsme buňky lidského hepatomu HepG2 a renální HK-2 buňky kultivované v 96-jamkových inkubovanými s apoptotickými induktory (tj. cisplatinou, staurosporinem, kamptotecinem) po dobu 6-48 hodin. Poté byly buňky inkubovány s Hoechst 33258 (2 ug/ml) a bylo detekováno zvýšení intenzity fluorescence po navázání barviva na DNA. Vyvinutý spektrofluorometrický test byl schopen detekovat jaderné změny způsobené všemi testovanými apoptotickými induktory. Poté jsme výsledky spektrofluorometrického testu porovnali s dalšími metodami detekujícími poškození buněk a apoptózu (tj. testy WST-1 a glutathionu, TUNEL, DNA ladder, aktivita kaspázy, exprese PARP-1 a JNKs). Zjistili jsme, že náš vyvinutý spektrofluorometrický test poskytuje výsledky se stejnou citlivostí jako test TUNEL, ale s výhodami rychlého zpracování, nízkých nákladů a vysokého výkonu. Protože jaderná kondenzace a fragmentace mohou být typickými markery buněčné smrti, zejména při apoptóze, předpokládáme, že spektrofluorometrický test by se mohl stát rutinně používanou metodou pro charakterizaci procesů buněčné smrti.

This bachelor thesis deals with the effect of glyphosate on the animal organism. The influence of individual selected groups of animals and humans is examined in different types of expermients. The bees in the behavioral study showed a reduced response to sucrose, a deterioration in short-term memory and a deterioration in the formation of ofor-foos relationships. Glyphosate reduced biodiversity in the amphibian population and also halved the toxicity at lower doses when the active substance was studied. Glyphosate also affects carp hepatocytes, which are subject to histological changes. The deteriorating health of the fish, which is infested with exoparasites, makes it easier for glyphosate to enter the body. In rats and rabbits, they cause reproductive problems. Human placental cells respond to glyphosate by reducing the production of the enzyme responsible for estrogen synthesis and thus to fertility problems. Glyphosate is more common in professional exposure and i tis similar in the population living in the immediate vicinity of its application.

The goal of this research is to provide linguists with visualisations for analysing the results of their hate speechannotation. These visualisations consist of a set of interactive graphs for analysing the global distribution ofannotated messages, finding relationships between features, and detecting inconsistencies in the annotation.We used a corpus that includes 1,262 comments posted in response to different Spanish online new articles.The comments were annotated with features such as sarcasm, mockery, insult, improper language, construc-tivity and argumentation, as well as with level of toxicity (’not-toxic’, ’mildly toxic’, ’toxic’ or ’very toxic’).We evaluated the selected visualisations with users to assess the graphs’ comprehensibility, interpretabilityand attractiveness. One of the lessons learned from the study is the usefulness of mixed visualisations that in-clude simple graphs (Bar, Heat map) - to facilitate the familiarisation with the results of the annotated corpustogether with more complex ones (Sankey, Spider or Chord) - to explore and identify relationships betweenfeatures and to find inconsistencies.

This study deals with the bioaccumulation of scarce metals, especially lanthanides, contained in red mud. The effect of red mud is studied on cultures of La4 mutant of the green alga Desmodesmus quadricauda and on red microalga Galdieria sulphuraria under different metabolic regimes with the addition of acidic extract of red mud.

Raphidiopsis raciborskii is a globally widespread bloom producing cyanobacteria that has been observed more frequently in temperate freshwater locations in previous twenty years, which is a considerable expansion regarding its original occurrence in tropical regions. The ability to produce health-threatening toxins, cylindrospermopsin (CYN) and saxitoxin, places this species to the centre of scientific research. The goal of this bachelor's thesis is to sum up the current knowledge on Raphidiopsis raciborskii, concerning mainly its ecology and phytogeography, and also to provide information about cyanotoxin cylindrospermopsin, which can be produced by R. raciborskii and also by other cyanobacteria species. Regarding cylindrospermopsin, I mainly focused on the chemical structure of the molecule, its biosynthesis, toxicity, methods of CYN detection and removal from drinking water.

The aim of this study was to verify the toxicity of selenium nanoparticles in an animal organism. Wistar albino rats were divided into five groups. Four groups of rats were fed a monodiet with added SeNP at doses of 0,5; 1,5; 3,0 and 5,0 mg Se/kg per feed dose. The experiment lasted 28 days. During this, the weight of the animals was measured every 7 days (0, 7, 14, 21, 28). After putting to death the animals at the end of the experiment, some blood parameters and histopathology of selected tissues were determined. Total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, total protein and albumin were diagnosed in the blood. Blood and liver selenium levels were analyzed and liver function tests were performed. Histopathological evaluation of liver and intestinal tissue was performed. The weight gain of the rats did not show differences between the tested groups. Compared to the control group, the selenium content in the blood and liver increased in the tested groups. However, selenium content in the liver did not increase in the test groups in a dose-dependend manner. No differences in TAC and ALP and AST aktivity were found. A significant reduction in ALT aktivity was observed in the test groups compared to the control group. SOD aktivity was reduced in the SeNP test group with 5 mg Se/kg compared to all other groups. GPx aktivity had a slightly increasing trend depending on the dose of SeNP, but without a significant (p

The diploma thesis focuses on the topic of environmental migration because of the Chernobyl nuclear accident in 1986. The main questions of the thesis are whether the Chernobyl accident is associated at any social level with environmental migration to the Czech Republic? To what time is the event socially framed? In what areas and how does the accident currently affect the lives of the environmental migrants? The diploma thesis has two research parts. The first part is a media analysis, which shows that the Chernobyl accident is mostly socially perceived as a matter of the past and is not associated with environmental migration to the Czech Republic. The second research part is based on anthropological research of semi- structured interviews with respondents. The result of this research is the division of radiation toxicity into five dimensions (political, biological, potential, reproductive, migration), in which the consequences of the Chernobyl accident continue to manifest themselves in the lives of environmental migrants. The dimensions of toxicity take place in different time frames, so the work also focuses on the temporality of modern accidents. The social perception of the Chernobyl accident as a finished event does not mean that it is no longer present in human lives. The aim of the...

Rozmanitosť sfarbenia plodov/semien púta pozornosť už od čias Darwina, avšak len veľmi málo sa vie o preferenciách určitých plodov/semien človekom. Atraktívne predmety sú človekom hodnotené pozitívne, lákajú jeho pozornosť, nepríťažlivé subjekty pôsobia naopak odpudivo. Cieľom práce bolo zistiť vzťah medzi vnímaním toxicity, estetiky a ochotou skonzumovať plody rastlín a stanovenie vplyv sfarbenia plodu na vnímanie jeho atraktivity. Výskumu sa zúčastnilo 195 žiakov základnej školy, ktorí sa na základe powerpointovej prezentácie, v rámci ktorej bolo prezentovaných 20 obrázkov cudzokrajných rastlín, konkrétne ich plodov, vyjadrovali k atraktivite, toxicite a ochote skonzumovať predložené plody. Bolo zistené, že žiaci boli ochotní skonzumovať vybrané plody bola štatisticky významne ovplyvnená vnímaním estetiky prezentovaných plodov a semien. Respondenti neboli schopní rozlišovať medzi jedlými a toxickými plodmi na základe ich sfarbenia. Červené plody boli hodnotené ako atraktívnejšie ako zelené a hnedé plody. Dievčatá hodnotili všetky skupiny plodov oveľa atraktívnejšie v porovnaní s chlapcami.

This bachelor thesis deals with phthalates and their part in living organisms. Phthalates are diesters of phtalicacid, which can be found all around us. They have had the negative focus of many studies and researches forquite a long time now because they are pollutants of the environment due their toxic effects on all living things. Phthalates are mainly used as a plastics oftener and they improve plastic qualities, but their negative side is that they leak into the material which they are in contact with. Phthalates can get into every part of the environment including us, humans. It´s negative effects on reproductive systems, kidneys and livers were proven by many studies. Furthermore, they have teratogenic and carcinogenic impacton living organisms. People facing the highest danger of phthalates are people working with them, gravid women, haemophiliacs and children.

Bacteria of the genus Xenorhabdus live as the natural symbionts of the entomopathogenic nematodes of the family Steinernematidae. They produce a wide range of toxic secondary metabolites of different chemical structure and effect. The synthesis of particular products is specific for each strain of Xenorhabdus. The thesis is focused on evaluating the impact of bacterial metabolites on facultatively entomoparasitic nematodes Oscheius myriophila, the free-living nematode Caenorhabditis elegans and the phytophagous potato cyst nematode Globodera rostochiensis. Target species of nematodes were exposed to 37 strains of Xenorhabdus bacteria, isolated from various species of Steinernematidae. Testing the impact of bacterial metabolites on O. myriophila and C. elegans nematodes was performed both by direct cultivation of target species on solid medium with live bacterial cultures as well as in sterilized liquid bacteria cultures. The effect of toxic substances on G. rostochiensis was evaluated only in selected sterilized bacteria cultures.

Zinc oxide nanoparticles are highly variable materials capable of producing positive and negative responses to their effects on plants. Negative effects are often associated with their excessive concentration, which can cause oxidative stress in plants.Conversely, suitable dosages lead to positive manifestations of growth and improvement in the properties studied. ZnO nanoparticles provide plants with a more acceptable form of zinc that is well accessible and easier to use. However, information about their pos-sible toxic effect in combination with another stress factor is lack. The aim of this work was to compare and evaluate the effects of zinc in the form of nanoparticles (ZnO NPs) with the effects of zinc bound in chelate bonding (Zn-EDTA), in combination with UV-C stress factor in plants Solanum lycoperscicum L. Results of this pilot experiment show that both ZnO and Zn-EDTA nanoparticles of 10.95 mg Zn2+ /l in combination with UV-C radiation have a negative effect on vitality and induce oxidative stress in treated plants. The decisive effect on the toxic effect was based on the concentration used and the form of zinc applied. Differences were expres-sed in expression levels of genes affected by oxidative stress. The results obtained from the expression analysis of the genes made it possible to observe the individual transcripts used to respond to oxidative stress and also to provide information on the possible sy-nergistic effect of UV-C radiation and zinc in both studied forms (Zn-EDTA and ZnO NPs).

The aim of this diploma thesis was to create an overview of colorantsauthorized for use in pharmaceutical products, conditions of their use and to characterize selected colorants in detail. The thesis is focused on the analysis on the health impact of the colorants. Their connection with child behaviour disorders and allergic reactions is described minutely. Part of the thesis is devoted to pointong out which colorants show the least negative impact on health as well as colorants with the highest incidence of side effects. A chapter describing the legislation on colorants in pharmaceuticals is also included. It is obvious, that natural colorants present a lower risk of side effects than synthetic colorants. Synthetic colorants with the highest incidence of side effects include the richly represented group of azo colorants, which causes ADHD in children and in hypersensitive patients, along with the natural colorant carmine, also allergy. Key words: colorants, natural colorants, synthetic colorants, allergic reaction, behaviour disorder, ADHD