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1

Ireland, Benjamin. "Amines in Olefin Metathesis: Ligands and Poisons." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34342.

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Olefin metathesis is a powerful tool for assembly of carbon-carbon bonds. Amines and related N-donors are problematic functional groups in Ru-catalyzed olefin metathesis - a well- documented, but poorly understood problem. The first part of this thesis focuses on amine-induced deactivation pathways; two of which are described in depth. Alkylidene abstraction, a previously unknown reaction for nitrogen nucleophiles, was observed for smaller and less Bronsted-basic amines. Deprotonation of the metallacyclobutane intermediate formed during catalysis is prominent for highly Bronsted basic or sterically bulky N-donors. Monosubstituted (and, by extension unsubstituted) metallacyclobutanes are particularly vulnerable to deprotonation. For each pathway, the fate of the alkylidene Ru=CHR functional group proved key in determining the nature of deactivation. Both pathways have been detected during catalysis, as evidenced by formation of diagnostic amine (RCH2NR2’) or substituted propene products. A combination of quantitative NMR and GC-MS analysis was used to identify these species on loss of the Ru-alkylidene functional group. The second part of this thesis focuses on incorporating amines into catalyst design – an under-utilized strategy in the context of Ru-catalyzed olefin metathesis. A modified Grubbs-type catalyst was developed featuring a bulky, relatively non-basic biaryldiamine ligand. Metathesis activity for this catalyst was comparable, and in some cases superior to the most widely-used homogeneous catalysts currently available. Several new, related Ru-benzylidenes were also prepared and fully characterized in conjunction with the mechanistic studies described above. Progress toward development of N-anion-containing metathesis catalysts is also discussed. Synthesis of Ru-hydride complexes originally intended for this purpose allowed for a fundamental study of the coordination chemistry and reductive elimination chemistry of the NPh2– anion.
2

Taylor, Erin N. Bickford Susan. "Specious poisons? reputation, gender, and democratic politics /." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,426.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.
Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Political Science." Discipline: Political Science; Department/School: Political Science.
3

Liu, Yan. "Toxic Cures: Poisons and Medicines in Medieval China." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467528.

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This dissertation explores the medicinal use of poisons in China from the third to the tenth century, which is when the major outlines of Chinese toxicological thought took shape. Challenging a widespread view that contrasts the benign naturalness of Chinese herbal remedies with the dangerous side effects of Western synthetic drugs, my research highlights the centrality of poisons to the practice and theory of medicine in China. Chinese doctors regularly relied on a large number of substances that they recognized as toxic to combat sickness, and identified toxicity as the central pillar for the classification of drugs. I argue that the boundary between poisons and medicines was always hazy in medieval China; it was not the substance itself, but how it was used and experienced that mattered. To examine this crucial yet ignored feature of Chinese medicine, my dissertation develops the following themes. The first is that drugs in medieval China were not fixed entities with unique effects. The effect of a given substance—whether it healed as a medicine, or sickened or killed as a poison, or altered a person in myriad other ways—varied both with usage and with processing. Subsequently, Chinese doctors developed a variety of techniques (the dosage, the drug combination, and the drug preparation) to mitigate the toxicity of a poison while preserving its therapeutic potency. Secondly, I highlight the intimate relation between bodily experience and the understanding of poisons. By studying the alchemical practice of ingesting toxic minerals, I show that the violent bodily effects induced by these substances were often perceived as confirmations of efficacy rather than worrying signs of pathology. My third theme is the circulation of toxicological knowledge across geographical and social domains. I argue that standardized textual knowledge propagated by the state was fluidly transformed in practice, contingent upon the availability of pharmacological ingredients and the needs of local people. Finally, I turn to non-poisons, especially foods, in Chinese pharmacy, and identify a distinctive character of Chinese medicine—the ingestion of mild substances to nourish the body and prolong life. Chinese medicine thus developed through the interaction of two related, but distinct enterprises—the fight against sickness, and the quest for ever-enhanced vitality.
History of Science
4

Malangu, Ntambwe. "Acute poisoning in three African countries: Botswana, South Africa and Uganda." Thesis, University of Limpopo (Medunsa Campus), 2011. http://hdl.handle.net/10386/674.

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Thesis (PhD (Epidemiology)-- University of Limpopo, 2011.
Acute poisoning constitutes one of the main reasons why patients visit emergency departments of hospitals. However, the burden and pattern of acute poisoning in African countries are not well established, hence the need for this study. This study was conducted in order to compare the patterns of acute poisoning in three countries, namely, Botswana, South Africa, and Uganda. Specifically, this study examined the similarities and differences in the patterns of occurrence of acute poisoning based on the sociodemographic characteristics of the victims, the toxic agents involved, and the circumstances of the incidents. The study was based on six papers published on the topic. Papers I and II about Botswana covered a period of 24 months (January 2004 - December 2005) and six months (January - June 2005) respectively. The data from Uganda, as reported in Paper III, covered a six-month period (January-June 2005); while studies in South Africa, Papers IV to VI, covered respectively six (January-June 2005) and 18 months (January 2000-June 2001). A re-analysis of data from Papers II to IV was conducted after recoding age category and the grouping of toxic agents. In total, the six Papers reported data on 1780 patients; 54.8% of them were male. The median age was 24 years in Uganda, but as low as 17 years in Botswana and South Africa. In Botswana and South Africa, acute poisoning incidents occurred mostly in children younger than 12 years old, then decreased among teenagers, and increased again among young adults, before decreasing among patients over 30 years old. On the contrary, in Uganda there was that less than 5% of children younger than 12 years who were victims of poisoning. There was an increase in the prevalence of acute poisoning among teenagers and young adults before a decrease occurred among adults over 30 years old. The overall case fatality rate was 2.1 %, ranging from 1.4% in Uganda, 2.4% in South Africa, to 2.6% in Botswana. With regard to similarities across the three countries, it was found that among teenagers, girls committed more deliberate self-poisoning than boys; while in young adults, men committed more self-poisoning than women. With regard to toxic agents, household products were involved in fatal Page 9 of 136 outcomes in all three countries; while agrichemicals were more involved in deliberate than accidental poisonings; food poisoning affected more females than males. With regard to disparities across the three countries, the age and gender of the victims, the circumstances of the incidents and the types of toxic agents played a significant role. With regard to gender, the majority of the victims were males in Uganda, females in South Africa; while in Botswana, females and males were affected equally. Among teenagers, the toxic agents most involved in the poisoning incidents were pharmaceuticals in Botswana; household chemicals in South Africa; but agrichemicals in Uganda. While the majority of incidents happened by accident in Botswana and South Africa, being respectively 76.7% and 59.1%; in Uganda, 64.5% of acute poisoning cases were deliberate self¬poisoning. Deliberate self-poisoning was responsible for 50% of deaths in Uganda, 30% in South Africa, but no death in Botswana. The majority of deaths occurred among teenagers in South Africa; in Uganda it was among adults over 30years; while in Botswana, the majority of deaths were distributed almost equally amongst children younger than 12years old and young adults. Diverse products were involved in fatal outcomes. In South Africa, pharmaceuticals, particularly drugs of abuse, cocaine and marijuana; as well as carbon monoxide, and organophosphates were involved in fatalities. While, in Botswana, the products involved were paraffin, traditional medicines, pharmaceuticals, food poisoning, plants, and snake envenomation. In contrast, in Uganda, alcohol intoxication, organophosphates, carbon monoxide, and some unspecified household products lead to fatalities. Household chemicals were involved in the deaths of victims in all three countries; but the extent of their involvement differed from country to country. This group of products was responsible of 75% of deaths in Uganda, half of deaths in South Africa, and in a third of deaths in Botswana. Agrichemicals were involved in the deaths of victims in Uganda and South Africa, but not in Botswana. They were involved in a quarter of deaths in Uganda and 10% of deaths in South Africa. Page 10 of 136 Plants and traditional medicines were involved in two-thirds of the deaths only in Botswana; while pharmaceuticals were involved in 40% of fatal outcomes only in South Africa. In conclusion, the contextual factors of each country led to a pattern of acute poisoning that showed some similarities with regard to the distribution of deliberate self-poisoning among females, teenagers, and young adult victims. However, there were disparities relating to the differential access to toxic agents, based on the age and gender of the victims. Moreover, though the case fatality rate was similar across the three countries, the distribution of deaths based on age, gender, circumstances of poisoning and types of toxic agents involved differed among the three countries. These findings suggest that multifaceted interventions should be implemented including policy development, enforcement of the existing legislation, and the establishment of a surveillance mechanism, in-service training of clinicians and revision of treatment guidelines. These interventions should be tailored to meet the specific realities of each country.
5

Fox, Mary Elizabeth. "Mechanisms of action of anticancer DNA topoisomerase II poisons." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239716.

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6

Kerry, Mark Anthony. "The design and synthesis of novel topoisomerase I poisons." Thesis, University of Sunderland, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245780.

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7

Lancaster, Cynthia Sue. "CDC45 function alters cell sensitivity to DNA topoisomerase I poisons." View the abstract Download the full-text PDF version, 2008. http://etd.utmem.edu/ABSTRACTS/2008-007-Lancaster-index.html.

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Thesis (Ph.D)--University of Tennessee Health Science Center, 2008.
Title from title page screen (viewed on July 16, 2007). Research advisor: Mary-Ann Bjornsti, Ph.D. Document formatted into pages (xii, 123 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 118-123).
8

Hobbs, Jeanette Roseanna. "Structural studies on the DNA binding modes of topoisomerase poisons." Thesis, University of Reading, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342117.

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9

Balosso, Jacques. "Mecanismes radiobiologiques des associations concomitantes radiotherapie-poisons de topoisomerase ii." Paris 7, 1997. http://www.theses.fr/1997PA077168.

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Les associations radiotherapie-chimiotherapie concomitante (arcc), constituent l'une des principales modalites de traitements anti-cancereux. Un tres grand nombre d'arcc sont possibles vu la variete des drogues et des schemas d'irradiation disponibles. Aussi, des informations fondamentales sur les interactions de ces therapeutiques aux niveaux cellulaire et tissulaire sont-elles indispensables pour fournir des rationnels aux cliniciens. Ce theme a ete aborde avec deux poisons de topoisomerase ii, la pazelliptine (pze) et l'etoposide (eto), grace a une approche cellulaire. Des cultures cellulaires humaines et murines de 5 lignees differentes ont ete utilisees en croissance ou en inhibition de contact. Les irradiations (rx), de 0 a 10 gy, ont ete faites par des photons gamma ou x. L'elution de l'adn sur filtre permit la quantification des coupures simples ou double brin, le clonage in-vitro la mesure des survies cellulaires, la cytometrie de flux l'etude de la distribution dans le cycle cellulaire, et la representation isobolographique normalisee l'evaluation de la synergie des arcc. L'arcc pze-rx sur les cellules en croissance peut produire un effet supra-additif. Il n'y a pas de modification pharmacocinetique, mais une augmentation du taux des lesions residuelles et une forte cooperation cytocinetique par les redistributions dans le cycle cellulaire. Avec eto-rx sur les cellules en croissance la supra-additivite evolue en fonction du temps selon une courbe biphasique revelant 2 mecanismes de sensibilisation. Le premier est une hypersensibilite durant la phase de reparation des radio-lesions sub-letales, le second une hypersensibilite de la phase g2 post-rx. La pze et le vp16 n'ont aucun effet sur les cellules quiescentes sauf aux tres fortes doses avec la pze. Il n'y a pas d'effet sur la reparation des lesions potentiellement letales. Les sequences ou les deux traitements sont les plus proches dans l'ordre rx drogue produisent les interactions les plus synergiques. C'est resultats sont discutes dans la perspective d'une application clinique. Une conception unifiee des concepts du laboratoire et de la clinique est proposee, basee en particulier sur la terminologie des isobologrammes et sur l'etude des effets tardifs des arcc en clinique.
10

TADDEI, PATRICK. "Pharmacodependance a l'amineptine : bilan du centre anti-poisons de marseille." Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX20086.

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11

KALFOUN, HENRI. "Intoxications digitaliques aigues : experience du centre anti-poisons de marseille." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX20009.

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12

Naṣr, Muḥammad Maḥmūd. "The differential impacts of regulation : empirical evidence from the chemical industry /." The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487265143147613.

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13

Poux, Hélène. "Poison et roman policier." Bordeaux 2, 1991. http://www.theses.fr/1991BOR2P070.

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14

Lewis, Louisa Joy. "Study of novel dual topoisomerase poisons as potential anti-cancer drugs." Thesis, University of Surrey, 2005. http://epubs.surrey.ac.uk/844572/.

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XR5944 and XR11576 are two potent DNA interactive agents, previously shown to be capable of stabilising topoisomerase I and II cleavable complexes in vitro. This thesis investigated the possibility that the mechanism(s) of action of these compounds may be unrelated to that of topo inhibition. These studies made use of a wide range of drug-sensitive and resistant cancer cell lines. It was demonstrated that both XR5944 and XR11576 retain potent cytotoxicity in cancer cell lines presenting with atypical drug resistance to single topoisomerase poisons. XR5944 showed less potency in cell lines expressing ABC-transporter proteins, but this may not be sufficient to compromise the activity of this potent anti-tumour agent in the clinical setting. The mechanism of XR11576 induced cytotoxicity was not affected by any of these transporters and from this and other observations it may possess a different mechanism of action from XR5944. An apoptotic response was observed in XR5944 and XR11576 treated cells. Factors such as Bax and t-Bid were expressed in increasing amounts in response to treatment and implicated the mitochondrial route of apoptosis in these compounds' mechanism of cell kill. Both XR5944 and XR11576 induced appreciable levels of DNA-protein crosslink formation and induced a p53 DNA damage response in drag treated cells. Differences in the timing of onset and extent of DNA damage and p53 induction were noticed between the two compounds. Overall, XR5944 was slower at causing these DNA interactive effects in line with the onset of cytotoxicity. However, this did not appear to pose any particular problems, such as scheduling of dosing, with regard to its in vivo activity, as shown by the work of others. These findings suggest that both XR5944 and XR11576 promote potent cytotoxicity in cancer cell lines showing multiple mechanisms of drug resistance and, therefore, should be of use in the clinic for the treatment of drug resistant tumours. The data presented in this thesis suggest that neither agent exerts its cytotoxicity via a topo directed effect. Furthermore, some of the data generated suggests that these two compounds may differ from each other in their mechanisms of action.
15

Jean, Decoster Catherine. "Effets des poisons des microtubules sur le cytosquelette aux doses cytotoxiques." Toulouse 3, 1999. http://www.theses.fr/1999TOU30253.

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Nous avons etudie l'effet des poisons des microtubules a des doses voisines des concentrations cytotoxiques sur le cytosquelette microtubulaire. Au cours de la premiere partie de notre travail, nous avons montre que les doses qui destabilisent partiellement le cytosquelette microtubulaire interphasique conduisent a la separation des centrosomes en deux unites fonctionnelles. La reversibilite de ce phenomene exige la presence de microtubules dynamiques. Ainsi, contrairement a l'opinion admise, les deux unites qui composent le centrosome sont fonctionnellement equivalentes et independantes pendant la majeure partie du cycle cellulaire. Ces resultats suggerent l'existence d'une heterogeneite de la sensibilite des microtubules a ces poisons et impliquent que la position des deux unites centrosomales, dans les cellules interphasiques, ne depend pas d'un lien physique mais d'un equilibre entre des forces generees par le cytosquelette. Dans la seconde partie, nous avons utilise la separation des unites du centrosome pendant l'interphase et la perturbation de la mitose pour determiner la cible pharmacologique de la vinflunine, un nouveau derive hemisynthetique des alcaloides de la vinca. La comparaison de l'action de la vinflunine avec celle de quatre alcaloides utilises en clinique montre que les effets cytotoxiques de ces composes antitumoraux sont compatibles avec une action destabilisatrice du cytosquelette microtubulaire interphasique et mitotique et confirme que la tubuline est la cible de ces composes.
16

Haro, Luc de. "Envenimation par serpents exotiques : bilan du centre anti-poisons de marseille." Aix-Marseille 2, 1992. http://www.theses.fr/1992AIX20102.

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17

Saad, Anwar Mudher. "The use of aflatoxin M1 monitoring for studying levels of exposure to aflatoxin for mothers and children." Thesis, University of Surrey, 1992. http://epubs.surrey.ac.uk/843217/.

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The present study was carried out in Abu Dhabi to evaluate the levels of contamination of mother's milk with the 4-hydroxy metabolite of aflatoxin B1. More than 22 nationalities living in Abu Dhabi were chosen as donors for this study. These different nationalities have different food habits. Most of those donors with the exception of U.A.E. have come to U.A.E. at ages 18 - 35 years. Their previous food habits have been looked into in comparison with the present style of life in U.A.E. The present study revealed that mother's milk is showing an increase in the level of aflatoxin contamination. The level of AFM; in mother's milk was as high as 3 ng / ml and, from 445 mother donors, AFM1 was detected in 99.5% of mother's breast milk. Analysis of the data shows no significant correlation between nationalities and total fat content of mother's milk with the level of AFM1. However, a detailed analysis of the composition of the milk fat revealed that milk rich in saturated fatty acid may be associated with high level of aflatoxin M1. In contrast milk containing high AFM1 usually had low levels of linoleic acid. High concentration of Lactose, the sole carbohydrate in human milk, has no association with AFM1 levels. It was found that a high protein content in the diet may be associated with high AFM1, in the mother's milk. Clearly the interaction between dietary factors, the presence of AFB1 in the diet, and the physiology of milk production are complex.
18

Nasr, Mohamed M. "The differential impacts of regulation : empirical evidence from the chemical industry." Connect to resource, 1986. http://rave.ohiolink.edu/etdc/view.cgi?acc%5Fnum=osu1262629235.

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19

Nemery, B. "The effect of O,S,S-trimethyl phosphorodithionate on the lung." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371047.

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20

Madra, Sukhdeep. "Hepatic interaction of polychlorinated biphenyls and iron." Thesis, Brunel University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316990.

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21

Turver, C. J. "The role of oxidant damage in asbestos genotoxicity." Thesis, Brunel University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371207.

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22

Khan, Farrukh Humayoon Rafique. "Studies on some of the effects of pesticides on earthworms." Thesis, Bangor University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263305.

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23

Bradley, Matthew Darren. "The accumulation and toxicity of copper, zinc and manganese in the farmed snail Helix aspersa maxima." Thesis, Bangor University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307215.

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24

Sims, Thomas Anthony. "A light and electron microscope investigation of the host-parasite relationship in the brains of mice with congenital toxoplasmosis." Thesis, De Montfort University, 1992. http://hdl.handle.net/2086/10749.

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Impregnation of the wall of intact tissue cysts in the brains of mice with congenital toxoplasmosis, with reduced silver salts and protargol silver suggested that it was composed, at least in part, of components derived from the neuronal cytoskeleton. Electron microscopy extended these observations and revealed that intact tissue cysts were separated from the extra-cellular compartment by a layer of neurofibrillae enclosed within the host cell membranes. Immunohistochemical staining confirmed that this layer contained neurofilament protein. Interior to this layer was a much convoluted parasitophorous vacuole membrane; exterior was the host cell membrane. In most cases, synaptic plates were noted on the outer plasma membrane. In no instance were tissue cysts observed either within neuroglial cells or in the absence of a host cell. Electron immunocytochemistry, using a rabbit polyclonal antiToxoplasma IgG as the primary layer in immunogold staining, revealed that Toxoplasma antigenwas widely distributed within the matrix of the cyst, being most concentrated in the proximity of the inner surface of the parasitophorous vacuole membrane. Relatively little Toxoplasma antigen was detected directly associated with cystozoites. Small amounts of antigen were detected directly associated with cystozoites, within host cell components exterior to the parasitophorous vacuole membrane and in the host neuropil, immediately adjacent to the tissue cyst. The inter-relationship between inflammatory lesions associated with small vessels, in close proximity to intact tissue cysts, suggest that there may be 'migration' of these cells, in an ordered sequence, towards the Toxoplasma antigen secreted from the tissue cysts.
25

Jewell, Christopher. "In vitro models for the assessment of skin xenobiotic metabolism." Thesis, University of Newcastle Upon Tyne, 1996. http://hdl.handle.net/10443/436.

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Skin subcellular fractions, keratinocytes, living skin equivalents (LSE) and percutaneous absorption using diffusion cells were examined as in vitro models for assessment of skin xenobiotic metabolism. Cytochrome P450 monooxygenase, esterase and glutathione-S-transferase (GST) activities were investigated in rodent, pig and human skin. CYP1A1 activity was detected in rat and pig skin microsomes by ethoxyresorufin-Odeethylation. CYP2B activity was detected in rat skin microsomes by pentoxyresorufin-Odepentylation. Neither were detected in human skin microsomes. Rat keratinocytes lost cytochrome P450 activity within several hours of being isolated from skin, and were not reliably induced following exposure to B-naphthoflavone. Cytochrome P450 activities were detected in the LSE after induction by 3-methylcholanthrene. Carboxylesterase activity was detected in skin, keratinocytes, and the LSE using 4- methylumbelliferyl heptanoate as the substrate. Induction of caboxylesterase activity by 3- methylcholanthrene was shown in the LSE but not keratinocytes. GST activity was shown in skin and keratinocytes, but induction was only shown in the LSE. The ability to induce xenobiotic metabolising activity suggests that enzyme induction may be linked to cell differentiation. GST's were localised at the basal layer of the epidermis. During percutaneous absorption, DNCB was metabolised to the glutathione (GSH) conjugate, limited by the GSH available in the skin. GSH conjugation of DNCB is thought to be a detoxification pathway preventing the immune response illicited by DNCB. Studies investigating the effect of age of rat on dermal xenobiotic metabolism revealed no differences between the neonate and mature rat with respect to cytochrome P450 monooxygenase activity or esterase activity. However, neonatal rat skin showed five fold lower GST activity and three fold higher reduced GSH levels. Pig skin showed similar levels of xenobiotic metabolising activity to human skin and showed a similar metabolic profile for DNCB during percutaneous absorption, supporting its use as a better model for human than rodent skin. The LSE was a good model for studies of human dermal xenobiotic metabolism particularly with the influence of inducing agents.
26

Fairhead, Heather. "The regulation of toxin production in Staphylococcus aureus." Thesis, University of Sheffield, 1998. http://etheses.whiterose.ac.uk/2985/.

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Staphylococcus aureus is a major human pathogen causing a wide range of illnesses from the trivial to the life-threatening. S. aureus produces many surface-associated and exoproteins, several of which have been implicated in its virulence. Production of these virulence determinants is co-ordinately controlled by several global regulatory elements in a growth phase dependent manner. The best characterised of these regulators are the accessory gene regulator (agr) and staphylococcal accessory regulator (sar). The agr locus comprises a quorum sensing system and encodes a signalling pheromone that autoregulates agr in a density dependent manner. Upregulation of agr expression leads to production of an mRNA transcript, RNAHI which is the actual effector of virulence gene expression. The RNAIII molecule upregulates several extracellular toxins including haemolysins, toxic shock syndrome toxin 1 (TSST-1) and epidermolytic toxin A (Eta), and down-regulates surface proteins such as protein A and fibronectin binding protein (FnBP) during late exponential growth and stationary phase. The regulation of toxin production by S. aureus is extremely complex and it is not yet understood exactly how this organism responds to environmental stimuli in order to mediate changes in virulence gene expression. In order to determine whether environmental signals are transduced via agr, the effect of several stimuli on both agr expression and a-haemolysin production was examined using a ß-galactosidase reporter gene fusion to the hid gene, which is encoded as part of the RNAIII transcript. A number of environmental stimuli were identified which led to changes in agr expression. Several of these stimuli resulted in different effects on a- haemolysin activity when compared to RNAIII levels. This suggests the presence of novel regulatory elements involved in the control of Hla production, independently of agr. In order to identify other novel regulators which interact with, or control, agr, transposon libraries have been created using Tn917 and Tn551. Two Tn917 transposon mutants were isolated as deficient in production of ß-haemolysin, which is also positively controlled by agr. These mutants were found to contain novel transposon insertions in the agr locus. Five Tn551 mutants were isolated which showed pleiotropic effects on virulence determinant levels and did not contain the transposon in previously mapped regulators. The Tn551 insertions may have therefore occurred in novel regulators of virulence determinant production. The regulation of toxin production by S. aureus in response to environmental stimuli is discussed.
27

Fitzpatrick, Sarah Anne. "Speciation analysis of arsenic and selenium by HPLC and mass spectrometry." Thesis, University of Plymouth, 2003. http://hdl.handle.net/10026.1/2702.

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New methodologies have been developed for the determination of arsenic and selenium species in a variety of environmentally important matrices. A simple liquid chromatographic separation technique based upon mini-column technology was developed to obtain a simultaneous, fast, efficient and reliable separation of relatively toxic from relatively non-toxic arsenic and selenium species. The relatively toxic arsenic and selenium species studied were inorganic Asv, AsIII, SeVI and SeIV. The relatively non-toxic species of arsenic and selenium studied were AsBet, DMA and Se Met. Optimum conditions were found to be the use of a Hamilton PRP X100 12-20 µm anion-exchange resin with column dimensions of 100 x 3 mm. The mobile phase utilized a 10 mM K2S04 solution at pH 10.2 with a flow rate of 1 ml minˉ¹ and a sample injection loop of 100 µ1. Total analysis time was under 7 minutes with limits of detection in the range of 2.0 - 10 µg kgˉ¹ for arsenic and selenium species, respectively. Work was undertaken, using HPLC-ICP-MS instrumentation, as part of a feasibility study, into the production and certification of six new reference materials; these being analyzed for the species of arsenic, in chicken, fish, rice and soil samples, and selenium, in wheat and yeast samples. Enzyme extraction techniques were used throughout, except for soil where a microwave H3P04 extraction was used. Efficiencies were in the range 90-100%. The results obtained provided speciation information as well as total elemental concentrations with no operationally defined limits. Speciation analysis requires that the endogenous species are extracted without modification of their chemical form or disturbance to the equilibrium existing between the various species present. Work was undertaken to identify and quantify the selenium species present in two samples of novel, previously unstudied, bio-natured nutrients, these nutrients being: i) a selenized yeast from a new process and: ii) a probiotic bacteria-based dried milk sample (Biogurt®). Specific interest was directed towards enzyme, MeOH and KOH and TMAH extraction efficiencies together with retention of species information. Selenium speciation was performed using ion-exchange HPLC-ICP-MS. It was found that the selenium content, in the form of SeMet, was adequately extracted from the yeast (Pharma Nord) that was used for method validation using protease, which yielding 90% of the total selenium. However, the determination of selenium and selenium species in the bionatured nutrients proved to be quite problematic. Methods that avoided species conversion with the highest extraction efficiencies were found to be: i) the use of protease for the yeast sample (19%) and; ii) the use of 0.01 M HCl for the Biogurt® (71%). Information obtained from speciation of these samples by anion and cation-exchange HPLC-ICP-MS was limited due to the low extraction efficiencies of any procedure undertaken for the samples, by the retention of the analyte on-column and by the lack of standards available for matching of retention times. HPLC-ICP-MS has proved an efficient tool for the identification and determination of arsenic and selenium species providing detection limits at µg kgˉ¹ levels. However, a major concern with this instrumentation is the unambiguous assignment of peaks which relies on the chromatographic purity of the signal and the availability of standards. Anion-exchange chromatography employing Hamilton PRP X100 resin with NH4HC03 (10 mM, pH 10.2 for arsenic and 10-50 mM, pH 5 for selenium species) with methanol (10 %, v/v) as the mobile phase allowed separation of the arsenic and selenium species investigated under conditions that were compatible for both HPLC-ICP-MS and HPLC-ESMS. Molecular ions and structural fragmentation patterns of these by tandem MS have facilitated the identification of chromatographic peaks obtained using HPLC-ICP-MS. In the analysis of marine algae, arsenosugars were the major species found, and in yeast the dominant species was found to be selenomethionine.
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Scarr, Andrew. "The toxicokinetics of imidacloprid in a target and non-target insect pest species." Thesis, University of Portsmouth, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310468.

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29

Scanlan, Clare M. "The development of algal-based toxicity testing for biocides used in marine industries." Thesis, Heriot-Watt University, 1985. http://hdl.handle.net/10399/1951.

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30

Yu, Tian-Wei. "Genotoxic damage induced by reactive oxygen species." Thesis, University of Surrey, 1997. http://epubs.surrey.ac.uk/764/.

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31

Bradburne, Susan Janet Ann. "Quantitative structure-toxicity studies of compounds in food contact materials." Thesis, Liverpool John Moores University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292314.

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32

Spears, Kevin. "Characterisation of Campylobacter jejuni toxins and their effects on clultured mamalian cells." Thesis, Nottingham Trent University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252309.

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33

So, Po Wah. "'1H NMR spectroscopic investigations into experimentally-induced hepatotoxic processes." Thesis, Birkbeck (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363065.

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34

Fentem, Julia H. "Hepatic microsomal metabolism and hepatotoxicity of coumarin in the rat and Mongolian gerbil." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303373.

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35

Bull, Sarah. "An evaluation of human cytochrome P450-transfected cell lines for metabolism-mediated toxicity studies." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301703.

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36

Bigot, Karine. "An embryotoxicological investigation using embryonic stem cells : a molecular and cellular approach." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324527.

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37

Ward, Rachel Ward. "Development of primary human keratinocyte cultures for studying chemical-induced skin irritation." Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241148.

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38

Horner, S. A. "An investigation of the metabolism-mediated cytotoxicity of xenobiotics in vitro." Thesis, University of Nottingham, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374318.

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39

Steer, Sarah Jane. "Problems inherent in developing in vitro tests for phototoxicity and immunotoxicity." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357820.

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40

Dhanjal, Perminder. "Investigation of the species differences and cytotoxic effects of coumarin and measurement of the cyctotoxic effects of various compounds in freshly isolated hepatocytes using several tests with particular interest in the MTT reduction assay freshly." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281599.

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41

Kaler, Balwant. "The role of bile acids in kidney failure as a result of obstructive jaundice." Thesis, University of East London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264409.

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42

Caldas, L. Q. A. "An investigation of the immunotoxicology of chromium, nickel and barium from inhaled metal fumes." Thesis, University of Bradford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374914.

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43

Asri, Kamarruddin. "Solid phase extraction techniques for the analysis of pesticides and drugs in biological specimens." Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249939.

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44

Tiernay, Linda Jane. "A comparative electrophysiological study of the effects of paralytic shellfish poisons on nerves, nerve-muscle, and neuronal cell types." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284693.

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45

Crosbie, Sarah Jane. "A toxicological study of skeletal muscle and its role in extrahepatic xenobiotic metabolism." Thesis, University of Newcastle Upon Tyne, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387385.

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46

Sword, Corinna Jane. "An in vitro study of aminoglycoside toxicity using established renal cell-lines." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244557.

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47

Hing, Jeremy P. "The application of non-linear mixed effects modelling to toxicokinetic data : population pharmacokinetics in preclinical studies." Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394740.

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48

Davis, Emma Louise. "Investigations of factors that influence the genotoxicity of environmental chemicals." Thesis, University of Newcastle Upon Tyne, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270808.

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49

Faiz, M. D. Abul. "Neuromuscular effects of the venom of Russell's viper." Thesis, University of Newcastle Upon Tyne, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317862.

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50

Devarajoo, Shashikala Devi. "Purification of the exotoxin(s) of Burkholderia pseudomallei." Thesis, University of Salford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360452.

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