UNT Libraries - 3 Matching Results

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The Effects of Glyphosate Based Herbicides on Chick Embryo Development

Description: Glyphosate based herbicides are among the most widely used herbicides in the world. The purpose of this study was to determine developmental toxicity of glyphosate, the active ingredient in the common herbicide Roundup, on developing chicken embryos. Few studies have examined toxic effects of glyphosate alone versus the full compound formulations of Roundup, which include adjuvants and surfactants. Adjutants and surfactants are added to aid in solubility and absorption of glyphosate. In this study chicken embryos were exposed at the air cell on embryonic day 6 to 19.8 or 9.9 mg / Kg egg mass of glyphosate in Roundup or glyphosate only. Chickens treated with 19.8 and 9.9 mg / Kg glyphosate in Roundup showed significant reduction in survivability compared to glyphosate alone treatments and controls. On embryonic day 18, embryos were sacrificed for evaluation of developmental toxicity using wet embryo mass, dry embryo mass, and yolk mass as indicators. Morphology measurements were taken on liver mass, heart mass, tibiotarsus length and beak length. Embryos treated with 19.8 mg / Kg glyphosate and 9.9 mg / Kg glyphosate in Roundup showed significant reductions in wet and dry embryo mass and yolk mass. Tibiotarsus length in 9.9 mg / Kg glyphosate in Roundup treatments were significantly reduced compared to 9.9 mg / Kg glyphosate treatments. Beak length was significantly reduced in 9.9 mg /Kg glyphosate in Roundup treatments compared to all other groups.
Date: August 2013
Creator: Winnick, Blake Edward

In Vitro Cortical Networks for Disease Modeling and Drug Evaluation

Description: In translational research, disease models in preclinical studies are used as media for discovery of drugs or novel therapeutics. Development of in vitro models for various neurological diseases that enable efficient pharmacological or toxicological screening has been ongoing but challenging. Recognizing the potential benefit of in vitro disease models, dysfunctions in the cortical neuronal networks were induced to mimic the functional pathology of neurological symptoms using microelectrode arrays. Two different disease states – tinnitusand excitotoxicity – were investigated and discussed. In this model, pentylenetetrazol-induced increase in spontaneous firing rate and synchrony in the auditory cortical networks was used as correlate of tinnitus. Potential tinnitus treatment drugs from several different classes – including the novel class of potassium channel openers – were screened and quantified. The potentialtherapeutic values of these drugs were also discussed as the basis for drug repurposing. Functional excitotoxicity was induced by cisplatin (a cancer drug that causes neurological sideeffects) and glutamate (the major excitatory neurotransmitter). As proof-of-principle that the model may contribute to expediting the development of therapeutics, cisplatin excitotoxicity wasprevented by the antioxidant D-methionine, while glutamate excitotoxicity was prevented by ceftriaxone (a modulator of a glutamate reuptake transporter). In the latter part of the study, with results linking two of the screened drugs L-carnitine and D-methionine to GABAA receptor activation, it was demonstrated that this model not only served as an efficient drug-screening platform, but can be utilized to functionally investigate the underlying mechanism of drugs. Inaddition, several practical or conceptual directions for future studies to improve on this in vitro disease model are suggested.
Date: December 2013
Creator: Wu, Calvin

Investigation of the Pharmacokinetics of Diazepam in Juvenile Channel Catfish (Ictalurus Punctatus)

Description: The presence of pharmaceuticals in the environment is becoming an increasing regulatory and scientific concern. Thus, the metabolic profile and bioconcentration potential of diazepam, a model benzodiazepine, were examined, as well as effects on the endocrine system in channel catfish. Through the use of specific and non-specific cytochrome P450 (CYP450) inhibitors, it was determined that CYP3A-like enzymes may play a role in the biotransformation of diazepam into temazepam; however, the isoform(s) required for the formation of other metabolites is still unknown. Overall, only around 7-8% of diazepam is biotransformed into two known metabolites. Due to the lack of inherent metabolism of diazepam in channel catfish, further analysis was conducted to determine the tissue-specific bioconcentration potential of diazepam in catfish. Various tissues were analyzed for the presence of diazepam as well as metabolites and bioconcentration factors (BCF) were calculated, which were all well below regulatory threshold values (> 2000). Additionally, modulation of the endocrine system by diazepam was examined by measuring steroid hormone concentrations and analyzing mRNA expression of selected steroidogenic enzymes and receptors. Two steroidogenic enzymes were modulated following diazepam exposure, indicating potential endocrine disrupting properties of diazepam. Together, these data suggest that diazepam exhibits low metabolic transformation rates in channel catfish, which may lead to accumulation of benzodiazepine compounds that may negatively affect the endocrine system. However, further studies should be aimed at identifying other steroidogenic enzymes and/or receptors that may be modulated following diazepam exposure.
Date: December 2013
Creator: Overturf, Carmen L.