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Mefloquine hydrochloride is an antimalarial agent that has been used for the past 40 years. Numerous reports of neurological side effects have recently led the FDA to issue a strong warning regarding long-term neurological effects. This warning lead to the U.S. Army’s Special Forces and other components to discontinue its use in July of 2013. Despite reported adverse side effects, mefloquine remains in circulation and is recommended to travelers going to specific Asian countries. Mefloquine has been used as a treatment for those already infected with the malaria parasite (blood concentrations ranging from 2.1 to 23 µM), and as prophylaxis (blood concentrations averaging 3.8 µM) (Dow 2003). The purpose of this study was to quantify Mefloquine’s toxicity using spontaneously active nerve cell networks growing on microelectrode arrays in vitro and to identify compounds that alleviate or reduce toxic effects. The current literature on mefloquine toxicity is lacking electrophysiological data. These data will contribute to research on the mechanism of adverse side effects associated with mefloquine use. Sequential titration experiments were performed by adding increasing concentrations of mefloquine solution to cultured neurons. Network responses were quantified and reversibility was examined. In each network, activity decreases were normalized as a percent of reference activity yielding a mean IC50 value of 5.97 ± 0.44 (SD) µM (n=6). After total activity loss, no activity was recovered with two successive medium changes. To test for network response desensitization resulting from sequential applications over 5-6 hr periods, one-point titrations at varying concentrations were conducted with fresh networks. These experiments yielded a single concentration response curve with an IC50 value of 2.97 µM. This represents a statistically significant shift (p < 0.0001) to lower concentrations of mefloquine, demonstrating that sequential applications result in network desensitization. After mefloquine exposures, cells were evaluated for irreversible cytotoxic damage. Over a 12-hour period under 6 µM mefloquine, process beading and granulation of somal cytoplasm were observed. At 8 µM mefloquine cell stress was apparent after only 10 minutes with major glial damage and process beading at 120 minutes. In this study, quinolinic acid served as a neuroprotectant at 20 µM. There have been multiple studies on the endogenous concentrations of quinolinic acid and current literature is quite variable. Immunocompromised individuals have some of the highest blood levels of quinolinic acid (up to 20 µM). With 30 min pre-applications of quinolinic acid, the mefloquine IC50 value shifted from 5.97 ± 0.44 µM (n=6), to 9.28 ± 0.55 µM (n=3). This represents a statistically significant change to higher mefloquine concentrations and demonstrates neuroprotection.

Bioassays for baseline toxicity, which measure toxicants’ non-specific effects, have been shown in previous studies to effectively correlate with the increased presence of pharmaceuticals, personal care products, endocrine-disrupting compounds, and other synthetic organics in treated sewage effluent. This study investigated how the baseline toxicity of anthropogenic compounds-spiked wastewater changed during the treatment of biofiltration and ozone oxidation, as measured by the bioluminescence inhibition of the Vibrio fischeri bacterium. The water quality parameters of dissolved organic carbon, seven common anions, and fluorescence spectroscopy were used to corroborate and collate with the toxicity results. Water quality was evaluated on two bench-scale soil filtration columns, which were configured for pre-ozonation and post-ozonation. Both systems’ soil aerobically removed similar amounts of dissolved organic carbon, and the reduction ranged between 57.7% and 62.1% for the post-ozonation and pre-ozonation systems, respectively. Biological removal of DOC, protein-like, humic-like, and soluble microbial product-like material was highest in the first 28.5 cm of each 114 cm-long system. While bioluminescence inhibition showed that ozonation was effective at lowering baseline toxicity, this study’s bioassay procedure was a very poor indicator of soil filtration treatment; both system’s effluents were significantly more toxic than their non-ozonated influents.

>Magister Scientiae - MSc / The interest in carbon-based nanomaterials, such as carbon-nanodots and graphene, has grown exponentially because these materials have unique properties and applications in the medical, electronic, clean energy and several other fields for biochemical sensing, energy conversion, photocatalysis, optoelectronics, etc. Carbon dots were discovered in 2004, yet very little research has been done on the colloidal stability thereof. Nanomaterials such as carbon dots will inescapably make their way to natural waters with an unknown environmental fate. Therefore, it is of great importance to understand the behaviour of carbon dots under the influence of certain environmental conditions such as pH, ionic strength, and in the presence of natural organic matter. / 2022

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

With the birth of “virtual worlds,” created a new space for social norms to evolve and change within a subset community. This thesis focuses on toxicity within the virtual world of EA DICE’s Battlefield V title. The goal of this research is to understand toxicity on a micro scale inside the world of Battlefield V from a gaming anthropological perspective. Along with understanding what toxicity looked like within the virtual world ofBattlefield V, the thesis obtained data for how the community and EA DICE employees perceived toxicity. This research has components of interviews with these members of the communities/staff as well as a netnography of the virtual world of Battlefield V gameplay. Findings and analysis were categorized under the themes of toxic language, power/freedom, virtual world creation, and gender toxicity. Battlefield V toxicity is ever evolving and shaped by player techne (player actions). Player chat consumes the majority of toxicity and therefore diving into toxic language was vital. Understanding the player perspective of power and freedom while gaming was just the first step as the thesis also dove into the developer’s perspective and analyzed the interviews with the backbone of Malaby’s (2009) contingency concepts to see how the developers have a large role to play when it comes to toxicity in games, even if they may not realize it. Just as in the “real world” the virtual world of Battlefield V also had a major theme of gender discrimination winessed and discussed via both community members and staff members of EA DICE. Overall, the goal of this research was not to find out if toxicity was “good” or “bad” but to simply shed more light on the complex topic within virtual worlds and open up research for other anthropologists to do further research on the topic.

The diploma thesis is primarily focused on the standardization of Daphnia magna breeding in laboratory conditions of the Department of Zoology, Fisheries, Hydrobiology and Beekeeping at the Faculty of Agronomy of the Mendel University in Brno. The main aim of the work is to simplify the preparation of medium for breeding Daphnia magna due to time saving. During testing, we were interested in births and mortality of individuals observed during 14-day tests in two media. We focus on chemical and physical properties of the media, namely the pH, temperature and intensity of the light.

In an attempt to determine mechanisms of certain aspects of ethanol- induced fetal damage, I have established a mouse model of the fetal alcohol syndrome based on the work of Chernoff (1977), using inbred C3H mice. Ethanol or its metabolite, acetaldehyde, was administered to female mice prior to and throughout gestation. Ethanol in doses of 6%, 10% and 20% ethanol derived calories and acetaldehyde 3. 9 mg and 11. 8 mg were administered daily in a nutritionally balanced liquid diet. An acute dose study was also undertaken, in which pregnant C3H mice were given. "binge" doses of 1ml of a 7. 35% solution of ethanol, twice daily through an orogastric tube, on days one and eight or four and twelve of gestation. The mice were sacrificed on day eighteen of gestation and the fetuses weighed and examined macroscopically. Some were sectioned using Wilson's method of free-hand razor blade sectioning (Barrow and Taylor, 1969), and the skeletons of the others were examined using a modified Dawson's method of skeletal preparation (Richmond and Bennett, 1938). A separate in vitro model based on the work of New (1967) was established, in which embryos of eight or nine days' gestation were explanted with visceral yolk sac intact from normal C3H mice. They were cultured for twenty-eight hours in rat serum containing various concentrations of ethanol or acetaldehyde (ethanol 1500, 3000 and 6000mg/l and acetaldehyde 7.4, 19. 7 and 39.4mg/l). During the last four hours of the culture period the embryos were labelled with one microcurie of tritiated thymidine (specific activity 5curies/mmol). At the end of the culture period the embryos were assessed morphologically, and then prepared for liquid-scintillation counting to determine DNA synthesis by measuring tritiated thymidine uptake. Small numbers of embryos from each group were used for autoradiographic studies in an attempt to quantitate the uptake of label in the various parts of the embryo. I found that ethanol given in chronic dosage in vivo was embryotoxic in all three doses studied. There was no evidence of ma tern al toxicity other than hyperactivity at the highest dose used and maternal jaundice in a small number of the 10% EDC and 20% EDC mice. Acetaldehyde given in chronic dosage in vivo produced no toxic effects on mothers or fetuses, other than a reduction in placental weights. Acute "binge" ethanol dosage of mothers on days one and eight or four and twelve of gestation did not appear to have any adverse effects on mothers or fetuses, apart from changes in placental weights. These findings should be viewed with caution, as the in vitro studies did not produce a corresponding result. In the latter study there was a marked time-related response, particularly for acetaldehyde. Ethanol given in vitro produced little evidence of toxicity except at dose levels which in the corresponding in vivo situation were extremely toxic to the mothers. Acetaldehyde, given in vitro in minute fractions of the harmless doses given to mothers in vivo, proved to be highly toxic to 8-day embryos and relatively non-toxic to 9-day embryos. This difference in sensitivity indicates that there must be some protective factor intervening between eight and ten days gestation - possibly the developing placenta may have a role here. From these findings I would suggest that acetaldehyde is a true teratogen, and the abnormalities produced in the chronic ethanol in vivo study were probably largely due to the action of acetaldehyde.

Aluminium is an element of increasing clinical importance. It not only has uses as a medicinal substance but also in recent years it has been shown to be the cause of considerable toxicity, particularly in the setting of chronic renal failure. Diseases that have been shown to be associated with aluminium, or in which it has been implicated, include dialysis dementia, renal osteodystrophy and Alzheimer's disease. This thesis has studied aspects of the interaction between aluminium and the kidney. The work has addressed two major issues. Firstly, a study is described where Malvin's stop-flow technique was used to determine any excretory/absorptive tubular site for Al in the pig kidney. Al was found to be excreted in the distal nephron of the pig kidney. Secondly, the toxic effects of Al in vitro on the DNA of pig kidney cell line LLC-PKl were investigated, in an attempt to elucidate some of the mechanisms of toxic action. DNA synthesis was measured using ³H-TdR incorporation. Over increases of both time (9-72 h) and Al concentration (0.01-8.0 mM), ³H-TdR incorporation was diminished. Effects were evident at concentrations as low as 0.05 mM Al. The production of DNA strand breaks was assessed by the increase in size of cell nucleoids (ie DNA in supercoiled form). Nucleoid size was analyzed in a Epics 753 Fluorescence Activated Cell Sorter interfaced with an MDADSII data acquisition and analysis system. After 90 min incubation with Al (over the concentration range 0.001-32 mM), an increase in nucleoid size was noted at concentrations above 0.05 mM. The data demonstrate that Al exerts an effect on kidney cells in vitro which is expressed as diminished DNA synthesis and production of DNA strand breaks. These effects on DNA may have important long-term implications on various disease states associated with Al toxicity.