Browsing by Subject "toxicity"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
Item Ecological Effects and In-situ Detection of Particulate Contaminants in Aqueous Environments(2012-07-16) Fuller, Christopher ByronThe ecological effects and mechanistic efficiency of chemical oil spill countermeasures must be evaluated prior to their ethical application during real spill response scenarios. Equally important is the ability to monitor the effectiveness of any spill response in real time, permitting informed response management. In-situ sensors are key components of such event based monitoring and continuous monitoring programs. This project investigates crude oil toxicity as a particulate suspension, suitability of in-situ instrumentation to measure crude oil suspensions, and the applicability of using acoustic backscatter to measure suspended solids and sub-surface oil droplet suspension concentrations. The ecological effects to inter- and sub-tidal sediment dwelling organisms exposed to crude oil, both treated with a chemical dispersant and un-treated, was evaluated. Elevated toxicity, expressed as percent mortality and reduced luminescence, and oil concentrations were observed in inter-tidal sediments receiving oil only treatments compared to oil-plus-dispersant treatments. Sub-tidal sediments showed heterogeneous distribution of crude oil with elevated amphipod mortality compared to no oil controls suggesting an oil-sediment aggregation mechanism. A separate laboratory scale study found that the soluble crude oil fractions were responsible for the observed mortality in pelagic species while the more dominant oil droplet fractions were relatively non-toxic. Subsequent studies focused on the in-situ detection of crude oil and particle suspensions in aqueous environments. The first showed that both in-situ fluorescence spectroscopy and Laser In-Situ Scattering Transmissometry (LISST) can effectively measure crude oil concentrations in aqueous environments. The applicability of the LISST implies that crude oil in an aqueous medium can be measured as a particle suspension. Acoustic backscatter (ABS) was investigated for its applicability as a surrogate measurement technology for aqueous particle suspensions. This study showed a log linear correlation between ABS and volume concentration (VC) over a variable particle size distribution. This correlation is due to the dependency of both ABS and VC to the particle size distribution. Log-linear ABS responses to oil-droplet suspension volume concentrations were also demonstrated. However, the inability to reproduce response factors suggests that more work is required to produce viable calibrations that may be used for sub-surface oil plume detection.Item Microvascular endothelial response to cocaethylene exposure: morphological and molecular observations(2004-11-02) Danyel Hermes Tacker; Anthony O. Okorodudu, Ph.D.; Robert H. Glew, Ph.D.; Norbert K. Herzog, Ph.D.; M. Tarek Elghetany, M.D.; Kathryn A. Cunningham, Ph.D.; Hal K. Hawkins, M.D., Ph.D.Cocaethylene (CE) is an active metabolite of cocaine and ethanol and is a toxicant of physiological relevance due to the high rate of cocaine and ethanol co-exposure (~80%) in cocaine abusers. It has prolonged action and increased potency on known physiological targets relative to the effect of cocaine. Since pathology in cocaine abusers is typically chronic and systemic, and CE persists in the body three to five times longer than cocaine, a link between CE and systemic disease in cocaine abusers was proposed. Consequently, this dissertation contains the studies that were used to test the hypothesis that the microvascular endothelium is a target tissue that is central in the pathogenic mechanism of cocaine-associated systemic disease, and that endothelial injury after CE exposure would result in dysregulation and altered barrier function due to changes in intracellular second messengers and signaling. To test this hypothesis, an in vitro model of CE exposure in human dermal microvascular endothelial cells (HMEC-1) was developed. Four Aims were designed to compartmentalize various components of the endothelial response to CE. The Aims included an array of methods to address cellular toxicity and dysfunction, including classical cytotoxicity and viability assays (Aim One), microscopic and electrical analyses of monolayer integrity (Aim Two), molecular analysis of second messengers, signaling molecule phosphorylation, and transcription factor DNA binding activity (Aims Three and Four). Aim One experiments demonstrated a lack of overt endothelial cytotoxicity caused by CE. Aim Two morphological analysis of endothelial intercellular borders and barrier integrity showed that CE exposure in the endothelial monolayers resulted in increased permeability, and hence a decrease in barrier integrity. These changes were observed temporally with alterations in cytosolic and total cellular free calcium ion (Aim Three), inositol 1,4,5 trisphosphate, and phosphorylated p38 mitogen-activated protein kinase concentrations, as well as changes in DNA binding activity and dimer composition of nuclear factor-kappaB (Aim Four). The observed changes suggest a distinct alteration of endothelial cell and monolayer function consistent with increased vascular permeability in vivo. Potential pathological outcomes of such effects include inflammation, vasculitis, systemic disease, and organ failure.Item Role of aggregation conditions and presence of small heat shock proteins on abeta structure, stability and toxicity(Texas A&M University, 2006-08-16) Lee, Sung MunAlzheimer??s disease (AD) is a neurodegenerative disorder that is one of such diseases associated with protein aggregation. Aβ is the main protein component of senile plaques in AD, and is neurotoxic when aggregated. In particular, soluble oligomeric forms of Aβ are closely related to neurotoxicity. In this dissertation, we examine the differences in Aβ aggregation intermediates, and final structures formed when only a simple modification in Aβ aggregation conditions is made, the presence or absence of mixing during aggregation. We show that intermediates in the aggregation pathway show significantly different structural rearrangements. The protein stabilities of Αβ species show that spherical aggregates corresponding to the most toxic Αβ species change their structure the most rapidly in denaturant, and that in general, increased toxicity correlated with decreased aggregate stability. In Alzheimer??s disease, even delaying Aβ aggregation onset or slowing its progression might be therapeutically useful, as disease onset is late in life. Small heat shock proteins (sHsps) may be useful for prevention of Αβ aggregation, since sHsps can interact with partly folded intermediate states of proteins to prevent incorrect folding and aggregation. In this research, several small heat shock proteins (sHsps) are tested to prevent Aβ aggregation and toxicity. sHsps used in this research are Hsp17.7, Hsp27, and Hsp20. All types of Hsp20, Hsp20-MBP, His-Hsp20 and His-Hsp20 without 11 residues in C-terminus, can prevent Aβ1-40 aggregation. Hsp20 also prevents Aβ toxicity in the same concentration ranges of it aggregation prevention activity. Hsp17.7 and Hsp27, however, can inhibit Αβ1-40 aggregation but not toxicity. A number of experiments to examine the mechanism of Hsp20 suggest that multivalent binding of sHsp to Aβ is necessary for the toxicity prevention activity. Conclusively, different Aβ incubation conditions in vitro can affect the rate of Aβ fibril formation, the morphology, the toxicity and the conformation of intermediates in the aggregation pathway. Hsp20 rather than other sHsps may be a useful molecular model for the drug design of the next generation of Aβ aggregation inhibitors to be used in the treatment of AD.Item Selenium nutrition of Morone hybrids including dietary requirements, bioavailability, toxicity and effects on immune responses and disease resistance(Texas A&M University, 2006-08-16) Jaramillo, Francisco , JrAquacultural production of hybrid striped bass (HSB) Morone chrysops ?? M. saxatilis is highly vulnerable to losses from bacterial pathogens such as Streptococcus iniae. Therefore, research was conducted to evaluate various dietary factors that may enhance immunocompetence and disease resistance of HSB. In the first experiment, purified and practical diets were supplemented with β-glucan and selenium in a factorial arrangement and fed to juvenile HSB for 6 wk followed by a S. iniae challenge. Weight gain (WG) and feed efficiency (FE) were higher for fish fed either practical diets or purified diets supplemented with selenium, but not those supplemented with β-glucan. Survival after disease challenge for fish fed the selenium-supplemented practical and purified diets was 75% and 35%, respectively. Because selenium supplementation also improved WG and FE, and because selenium and vitamin E have complementary biochemical functions, a second experiment evaluated potential interactions by feeding purified diets with or without vitamin E or sodium selenite (Na2SeO3), singularly or in combination, for 12 wk. Dietary selenium significantly affected whole-body selenium concentration but there was no effect of dietary selenium, vitamin E or their interaction on WG, FE, survival or blood neutrophil oxidative radical production. Three additional 12-wk experiments were conducted to establish selenium essentiality, toxicity, tissue deposition, dietary requirements, bioavailability and nonspecific immune responses using purified diets with a basal selenium level of 0.11 mg/kg. In one experiment, diets had selenium concentrations of 1.19, 2.00, 5.17 and 21.23 mg/kg from Na2SeO3. Another experiment had selenium concentrations of 0.90, 1.26 and 2.55 mg/kg from seleno-DL-methionine. The third trial utilized selenium from Na2SeO3, seleno-DL-methionine and selenium yeast at approximately 0.15, 0.30 and 0.60 mg/kg diet. No overt selenium deficiency signs were observed in any of the three latter experiments, but based on selenium retention values, a minimum dietary requirement of approximately 0.1 mg/kg was estimated. Selenium toxicity was observed in fish fed the diet containing more than 20 mg/kg. Bioavailability of selenium sources was ranked as seleno-DL-methionine > selenium yeast > Na2SeO3.