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MAGLIE, M. DE. "BIODISTRIBUTION AND TOXICITY OF METALLIC NANOPARTICLES:IN VIVO STUDIES IN MICE." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/487404.
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In the last decade, nanotechnology has emerged as one of the fastest growing area of science. This is a highly promising field for the generation of new engineering applications, consumer products, medical healthcare and medicine. However, the increasing development of nanomaterials (NMs) is not supported by in vivo studies taking systematically into consideration nanoparticles (NPs) types, doses and period of treatment that would allow to forecast possible adverse outcomes that might occur upon human exposure.
In our studies, fully characterized silver nanoparticles (AgNPs) and iron oxide nanoparticles (IONP), designed for cancer treatment, were used to assess biodistribution and potential toxic effects after single intravenous and repeated oral administration in mice.
Unexpected histopathological findings, strictly related to the physicochemical properties, i.e. size and vehicle used for the NPs synthesis, were observed after intravenous administration. This confirms that a complete characterization of NPs is of the most importance for the identification of in vivo outcomes. NPs mainly localized in organs containing large number of specialized tissue-resident macrophages belonging to the mononuclear phagocyte system. The retention of NPs in these tissues raises concerns about the potential toxicity.
The 28 days repeated oral administration of AgNPs demonstrated that the brain is the organ where Ag accumulation takes place. In fact, Ag it is still detected in brain after the recovery period because of its low clearance. Morphological changes observed in the blood brain barrier (BBB), and the involvement of glial cells in response to AgNPs administration, suggested a perturbation of brain homeostasis that should be taken into consideration and further investigated.
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Hsieh, Heidi. "Investigating Zinc Toxicity In Olfactory Neurons: In Silico, In Vitro, And In Vivo Studies." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1447070598.
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Tietze, Nicole. "Studies on Efficiency and Toxicity of in vivo Delivery Systems for siRNA and plasmid DNA." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-99633.
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Wiley, Faith Elizabeth. "Extraction method development and in vivo and in vitro toxicity studies of the etiologic agent of avian vacuolar myelinopathy." Connect to this title online, 2007. http://etd.lib.clemson.edu/documents/1181666264/.
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Chamberlain, Mark Peter. "The toxicity of methyl iodide : in vivo and in vitro mechanistic studies in the rat nasal cavity and cerebellum." Thesis, Liverpool John Moores University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244461.
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Evans, Andrew. "In vitro and ex vivo studies on the toxicity and efficacy of a selection of non-viral transfection reagents." Thesis, Liverpool John Moores University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403283.
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余慶聲 and Hing-Sing Yu. "Studies on the toxicity and teratogenicity of cadmium on mouse pre-embryos in vitro and in vivo with special reference to theirsubsequent development." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1987. http://hub.hku.hk/bib/B31231457.
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Yu, Hing-Sing. "Studies on the toxicity and teratogenicity of cadmium on mouse pre-embryos in vitro and in vivo with special reference to their subsequent development /." [Hong Kong] : University of Hong Kong, 1987. http://sunzi.lib.hku.hk/hkuto/record.jsp?B1221579X.
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Ahn, Sunjoo. "Novel Antimitotic Compounds with Potent In Vitro and In Vivo Antitumor Effects: the Use of Pharmacokinetics, Metabolism, Efficacy, and Toxicity Studies." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1281966697.
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Giuliano, Francesco. "Evaluation of the activity and selectivity of non-steroidal anti-inflammatory drugs in vivo, ex vivo and in vitro." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367598.
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Woodbridge, Nesta. "Mechanistic studies relevant to chromate toxicity." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267077.
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Tether, Angela Lynn. "Enzymatic and toxicity studies of ionic liquids." Thesis, Queen's University Belfast, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603419.
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This thesis contains work primarily pertaining to two different projects, with the majority of work carried out at Queen's University of Belfast, QUS, along with some at TUDelft, Delft University of Technology, Delft, NL. The first project was concerned with the development, optimisation, and implementation of high throughput inexpensive, and facile toxicity testing methods for use with novel ionic liquids. Approximately one hundred ionic liquids were tested against two strains of bacteria - one Gram negative and one Gram positive. The results varied from no-to-low inhibit ion zones to large inhibition zones, indicating toxicity to the organisms tested. The second project was concerned with the use of ionic liquids as co-solvents in a biocatalytic reaction involving novel enoate reductase enzymes. Approximately twenty ionic liquids, both water-miscible and water-immiscible were tested. Two methods were used for the analysis of the reactions performed, ultraviolet spectrophotometric analysis and liquid -liquid extraction combined with gas chromatographic analysis. The water-immiscible ionic liquids garnered better results when tested with the enzymes of interest than did the water-miscible ones.
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Khojasteh-Bakht, Siamak C. "Studies on metabolism and toxicity of menthofuran /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/8157.
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Yu, Xin. "Studies of polyglutamine expanded Ataxin-7 toxicity." Doctoral thesis, Stockholms universitet, Institutionen för neurokemi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-121116.
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Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant inherited neurodegenerative disease for which there is no cure. SCA7 belongs to the group of polyglutamine disorders, which are all caused by the expansion of a polyglutamine tract in different disease proteins. Common toxic mechanisms have been proposed for polyglutamine diseases; however the exact pathological mechanism(s) are still unclear. The aim of this thesis was to identify and characterize the molecular mechanisms by which polyglutamine expansion in the ATXN7 protein cause SCA7 and how this can be counteracted. We found that mutant ATXN7 can be degraded by the ubiquitin proteasome system (UPS) and autophagy, the two main cellular degradation pathways. However aggregation stabilized the protein against degradation. Moreover, we found that mutant ATXN7 blocked the induction of autophagy by interfering with p53 and the ULK1-ATG13-FIP200 complex. Pharmacological stimulation of autophagy ameliorated aggregation, as well as toxicity. We also found that oxidative stress plays an important role in mutant ATXN7 toxicity and that the oxidative stress is generated by activation of NADPH oxidase 1 (NOX1) complexes. Furthermore, we showed that the increased NOX1 activity, together with polyQ expanded ATXN7 mediated disruption of the transcription factor p53, results in metabolic alterations in SCA7 cells. The expression of key p53 regulated metabolic proteins like AIF, TIGAR and GLUT1 was altered in SCA7 cells and resulted in reduced mitochondrial respiration, a higher dependence on glycolysis and reduced ATP levels. In summary, our data indicate that mutant ATXN7 mediated dysregulation of p53, resulting in autophagic and metabolic alterations, could play a key role in SCA7 and possibly other polyglutamine diseases.
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Faridwajidi, Mustafa Fadzil. "Transgenic Drosophila as an in vivo model of human drug metabolism." Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254027.
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Ng, Jasmine Christina. "Toxicity of cadmium in hepatocytes." Thesis, University of Surrey, 1986. http://epubs.surrey.ac.uk/844145/.
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Freshly isolated hepatocytes from fed and starved rats were used as a model in the investigation of the mechanisms by which cadmium chloride exerts its toxic effects at the cellular level. Exposure to cadmium chloride resulted in a slight decrease in viability, more pronounced in hepatocytes from starved rats. Morphological changes preceded the increase in membrane permeability. Hepatocytes exhibited a rapid initial uptake of cadmium chloride, followed by a second slower phase. The accumulation of more metal in hepatocytes from starved rats may contribute to their enhanced susceptibility to cadmium chloride. Adverse metabolic effects of cadmium chloride included an increase in the lactate:pyruvate ratio in hepatocytes from fed rats, with a concomitant decrease in the 3-hydroxybutyrate:acetoacetate ratio in hepatocytes from fed and starved rats. Incubation with cadmium chloride resulted in increased glycogenolysis and glycolysis. Decreased rates of gluconeogenesis from lactate and pyruvate reflected the decreased uptake of gluconeogenic precursors. Studies of intracellular lactate concentrations could not resolve whether the decrease in gluconeogenesis was due to an inhibition of lactate transport into the hepatocyte or due to a decrease in its metabolism. Cadmium chloride caused a slight decrease in the basal and pyruvate-stimulated rates of cellular respiration, a marked dose-related decrease with lactate, and no significant effects with succinate. Carbonyl- cyanide-m-chlorophenylhydrazone was less effective in stimulating respiration in hepatocytes incubated with cadmium chloride, this effect being more pronounced with lactate and pyruvate than with succinate. Cadmium chloride had little effect on the uncoupled rates of FADH2 oxidation with succinate suggesting that electron transport from succinate dehydrogenase to cytochrome a/a3 was not impaired. The results from these studies suggest a primary effect of cadmium chloride on mitochondrial function and cellular energy production, resulting in secondary metabolic changes in an attempt to overcome the declining levels of ATP within the cell.
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Van, der Schoor Ciska. "An in vivo and in ovo evaluation of the toxicity of Sibutramine." Diss., University of Pretoria, 2014. http://hdl.handle.net/2263/46008.
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Sibutramine hydrochloride monohydrate is a weight loss agent banned from most global markets due to reports of serious adverse events including death. It is classified as a serotonin-norepinephrine reuptake inhibitor and acts within the central nervous system by inhibiting the reuptake of these neurotransmitters essentially influencing satiety and also energy expenditure. Despite its ban, sibutramine is still available for use in some countries and is often an unlisted ingredient in herbal or natural weight loss products. This leads to the oblivious and unintentional consumption of this compound which is of great concern especially if used by pregnant women. The aim of this study was to investigate the possible toxic and teratogenic effects of sibutramine by using a Spraque Dawley rat and an in ovo chick embryo model. The Sprague Dawley rat was used as in vivo model and animals were divided into three experimental groups, each consisting of 12 animals (6 males, 6 females). Rats were administered sibutramine over a 28 day period according to their assigned experimental groups namely control (C; sterile H2O), Low dose (LD; 1.32 mg/kg) and High Dose (HD; 13.2 mg/kg). On the day of termination blood was collected for various analyses which included biochemical tests for liver and kidney function, hormonal changes as well as the investigation of coagulation profiles. Brain, heart, lung, kidney and liver tissue of each animal was harvested for investigation of tissue and cellular structure.
Rats were weighed daily and this data suggested that sibutramine was well tolerated by all animals, with only the female rats in the HD group showing a significant 8.2% decrease in their rate of weight gain. Biochemical data of liver and kidney function in all groups were normal. Thyroid hormone levels were comparable to control values though cortisol levels were lowered in the HD female group, a finding which correlates with the observed weight loss.
Investigations of the ultrastructural morphology of the platelets and fibrin networks revealed differences between the experimental groups that are consistent with changes associated with a procoagulable state. Brain, kidney and liver tissue morphology appeared normal upon investigation, the latter confirming the biochemical findings. Examination of cardiac tissue revealed a slight increase in collagen deposition between the muscle fibers and ultrastructural analysis of lung tissue showed thickening of the alveolar walls, decreased intra-alveolar space and drastic increases in collagen deposition in the sibutramine-exposed groups. These findings were dosage dependant. The in ovo model was implemented with ephedrine, a known teratogen, as positive control. Three control groups were included to ensure the efficacy of the method. Eight experimental groups, each containing sixteen eggs, were exposed to four different concentrations of each drug (i.e. 0.5, 2.5, 5.0, 10.0 μmol). The brain, heart, liver and kidneys were harvested on embryonic day thirteen for morphological analysis. Macroscopic evaluation revealed that both drugs caused congenital abnormalities which included ventral wall and limb defects as well as growth retardation and increased mortality. Sibutramine was found to have a greater teratogenic potential than ephedrine.
Histological investigation of kidney and brain samples of embryos revealed no morphological differences between the various experimental groups. Livers and hearts of embryos exposed were severely affected by both compounds in a dose dependant manner. Replacement of myocardium with adipose and connective tissue was observed in cardiac tissue, which is characteristic of muscular dystrophy. Severe liver steatosis was also evident.
In conclusion, results from this animal-based study show that, at concentrations which are not toxic to the liver or kidneys, sibutramine administration led to increased coagulation, moderate cardiac and excessive lung fibrosis within the Sprague Dawley rat model. This indicates significant toxicity with the cardiac and respiratory system being more susceptible targets. In addition sibutramine was shown to possess greater teratogenic effects than ephedrine. Both drugs caused cardiac dystrophy and liver steatosis resulting in extensive liver and heart damage. Understanding the underlying mechanisms involved in the pathogenesis of these findings strongly emphasize an important area for future research.<br>Dissertation (MSc)--University of Pretoria, 2014.<br>tm2015<br>Anatomy<br>MSc<br>Unrestricted
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Cookson, Mark R. "Studies of activation and toxicity in cultured astrocytes." Thesis, University of Salford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308094.
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Allan, Simon G. "Studies on the gastrointestinal toxicity of Cis-platinum." Thesis, University of Aberdeen, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330087.
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Old, Sally Louise. "Focal lesions in toxicity studies : methods and models." Thesis, De Montfort University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391200.
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Hodges, Geoffrey. "QSAR studies of surfactant toxicity to Daphnia magna." Thesis, Liverpool John Moores University, 1997. http://researchonline.ljmu.ac.uk/4910/.
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The inherent nature of surfactants to aggregate at surfaces makes measurement of log P (octanoll water partition coefficient) for these substances extremely difficult. It is possible, however, to calculate a log P descriptor based on the method described by Hansch and Leo (1979). Work presented in this thesis describes the study of the acute toxicity of sulphonated esters (FAES) of general formula R-CH(S03"Na +)-C02-R' to Daphnia magna. Due to structural similarities of this class of anionic surfactant to linear alkylbenzene sulphonate (LAS), it was considered that the log P based QSAR originally developed to describe the toxicity of LAS to D. magna (Roberts, 1989) also would be a good predictor of the acute toxicity for FAES substances. Results of the toxicity studies showed that FAES substances were less toxic than predicted. However, when plotted against log P' Calculated using the conventional fragment approach of Hansch and Leo with the addition of a position dependent branching factor (PDBF) to account for water sharing between hydrocarbon chains, the regression slope was para"el to but distinct from that of LAS. This indicated that either FAES substances were not acting as by the same mode of action as LAS or that modification of the log P calculation was required. Further studies of the toxicity of binary mixtures of FAES with known polar and non-polar narcotics, established that FAES exhibited concentration addition with LAS and phenol. This indicated that they behaved with a similar mode of action and it would be expected that LAS and FAES would share the same QSAR. The difference of the regression slopes of FAES and LAS observed? earlier, therefore, suggested the requirement of a modification to the original log P calculation. The modified proximity factor developed in this thesis considers the effects of relative size of proximal polar fragments on log P.? Spherical hydration sheaths surrounding each fragment were assumed and 'overlapping volumes calculated for fragments at different carbon separation. When incorporated into the log P calculation, the new log P values now allow toxicity values for LAS and F AES substances to be incorporated into the same QSAR.
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Hopley, J. P. "Toxicity studies in a differentiating epidermal keratinocyte culture." Thesis, University of Surrey, 1986. http://epubs.surrey.ac.uk/847531/.
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A keratinocyte culture derived from rat sublingual epithelium has been developed and characterised both morphologically and enzymically. Morphologically the culture closely resembles that found in vivo. The culture has been studied comprehensively using light and electron microscopy (scanning and transmission). The culture procedure has been optimised such that minimal amounts of time and materials are required. The culture, although heteroploid, shows a high degree of homogeneity with minimal fibroblastic contamination. Total adhered protein, total DNA content, 3H-thymidine incorporation, ornithine decarboxylase activity, acid phosphatase activity, prolinase and malate dehydrogenase activity have been studied at various phases in the cultures growth cycle. An initial study using 3,3',4,4' tetrachlorobiphenyl indicated that acid phosphatase, prolinase and total protein may be the best parameters for studying toxic insult in these cells, together with morphological examination by electron microscopy and light microscopy using acridine orange as a stain. Subsequently, comparisons of the 3,3',4,4' and 2,2,4,4' tetrachlorobiphenyl isomers, benzo(a)pyrene and 20-methylcholanthrene were made. Acid phosphatase and prolinase appeared to be useful markers of the toxic effects of these compounds showing alterations consistent with some in vivo findings. These changes were observed at concentrations of the compounds that did not produce significant cytotoxicity. Morphological examination showed changes with some similarities to some carcinomas in vivo. The effects of these compounds on keratin production within the cells has also been undertaken. A comparison has also been made of the relative toxicities of several compounds in the keratinocyte culture and in the human embryonic lung fibroblast line (BCL-Dl); the keratinocyte system appeared to be more sensitive to irritant compounds. Studies of the metabolic capabilities of the culture using benzo(a)pyrene as substrate have also been undertaken. Although the capacity of these cells to metabolise foreign compounds was low, they show hydroxylation, glucuronidation and sulphation activity. In longer term tests (14-21 day), the system shows enhanced sensitivity, the point of commitment of the culture (ie., differentiation and stratification) being a critical time. The methods used showed good reproducibility and were easily performed. The system may, therefore, provide a useful sensitive screening test for detection of compounds affecting differentiation (e. g irritants and carcinogens).
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Bicer, Sabahattin. "Efficacy/toxicity studies of amiodarone in animal models /." The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486546889383936.
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Shittu, Adenike Rofiyat. "Toxicity Studies Of Per- and Polyfluoroalkyl Substances (PFAS)." Bowling Green State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1625018658596765.
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Rodrigues, Andreia do Carmo Martins. "Mercury toxicity and bioaccumulation: lab & field studies." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/7457.
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Mestrado em Biologia Aplicada - Toxicologia e Ecotoxicologia<br>This work aims to evaluate the toxicity, bioaccumulation and biomagnification of
mercury and it is divided into a laboratory and a field component. The
laboratory component was divided into two parts and the field component was
conducted into an estuarine environment in Ria de Aveiro, Portugal.
In the laboratory we started by evaluating the toxicity of mercury for different
aquatic organisms, using mercury concentrations that ranged between 0.5 μg/L
to 2.4 mg/L. The chosen species used in this assay to evaluate mercury toxicity
were the models: Pseudokirchneriella subcapitata, Daphnia magna and
Chironomus riparius and the autochthonous species: Chlorella vulgaris, Lemna
minor and Daphnia longispina. Mercury showed to be toxic to all testes
species, with EC50 values ranging from 7.3 μg Hg/L (immobilization test of D.
longispina) to 1.58 mg Hg/L (immobilization test of the larvae of C. riparius).
The assay showed that even low doses of mercury can cause significant
effects at the levels of primary producers, the base of the trophic chain.
In the secondary laboratorial assay, an aquatic trophic chain was simulated
using the primary producer P. subcapitata, the primary consumer D. magna
and the secondary consumer Danio rerio. The trophic chain mercury
contamination process was initiated exposing an algae culture to inorganic
mercury (10 μg Hg/L), resulting in the accumulation of 70% of the available
mercury in the primary producer. The contaminated algae were then used as
food supply to the specie D. magna and subsequently D. magna specimens
were used as food to the secondary consumer. After 14 days of exposure D.
magna accumulates 0.14 μg Hg/g, whereas the final average concentration
obtained in the muscle of the fish D. rerio after 21 days was 0.27 μg Hg/g (wet
weight). All test species accumulate mercury along the time of exposure; the
higher biomagnification occurred from the microalgae P. subcapitata to the
mircrocrustacean D. magna, enhancing the crucial role of primary producers in
the bioconcentration of mercury from the water column along the trophic chain.
Fieldwork was conducted in the Ria de Aveiro, in two specific sites (Cais do
Bico and Barra) that were already characterized regarding dissimilar
environmental mercury contamination levels. Mercury levels were evaluated in
the water column (total mercury), sediments (total and organic mercury) and in
juvenile fish Liza aurata inhabiting the area (total and organic mercury). Cais do
Bico site, located near the source of contamination showed the highest values
of total mercury: 68 ng/L in the water column, 0.19 μg/g in the sediments and
0.07 μg/g in fish. The site distant from the source of mercury (Barra) presented
a great amount of organic mercury in the sediments (0.02 μg/g) and a higher
percentage of organic mercury in fish muscle (96%). The study indicates that,
although mercury discharges have already stopped in the end of the last
century, mercury stored in sediments continues to be ressuspended to the
water column, becoming bioavailable to biota. The adoption of juvenile
specimens provides information on short-term variations of mercury
concentrations in the environment.<br>O objectivo deste trabalho é avaliar a toxicidade, a bioacumulação e a
bioamplificação de mercúrio. O trabalho apresenta uma componente
laboratorial e uma componente de campo. A componente laboratorial foi
dividida em duas partes e a componente de campo foi realizada num ambiente
estuarino, Ria de Aveiro, Portugal.
Na componente laboratorial, começou por se avaliar a toxicidade do mercúrio
para diferentes organismos aquáticos, testando-se concentrações de mercúrio
entre 0,5 μg/L e 2,4 mg/L. As espécies teste escolhidas para avaliar a
toxicidade do mercúrio incluíram espécies modelo: Pseudokirchneriella
subcapitata, Daphnia magna e Chironomus riparius, e espécies autóctones:
Chlorella vulgaris, Lemna minor e Daphnia longispina. O mercúrio revelou ser
tóxico para todas as espécies, obtendo-se valores de EC50 que variaram de 7.3
μg Hg/L (teste de imobilização de D. longispina) a 1,58 mg Hg/L (teste de
imobilização das larvas de C. riparius). Este ensaio demonstrou que pequenas
doses de mercúrio provocam efeitos consideráveis ao nível dos produtores
primários, base das cadeias tróficas.
Num segundo procedimento experimental construiu-se uma cadeia trófica
aquática, constituída pelo produtor primário P. subcapitata, pelo consumidor
primário D. magna e o consumidor secundário Danio rerio. A contaminação
iniciou-se pelo meio de cultura das algas com 10 μg Hg/L, do qual estas
acumularam 70% do mercúrio disponível. Esta espécie foi usada como
alimento para D. magna, que por sua vez, foi usada como alimento para o
consumidor secundário Danio rerio. Após um período de 14 dias de teste D.
magna acumulou 0,14 μg Hg/g. A concentração média obtida no músculo de
D. rerio, após 21 dias de teste, foi de 0,27 μg Hg/g, peso fresco. Todos os
organismos acumularam mercúrio ao longo do tempo de exposição, sendo que
a maior bioamplificação de mercúrio ocorreu da microalga P. subcapitata para
o microcrustáceo D. magna, reforçando assim o papel crucial dos produtores
primários na bioconcentração de mercúrio da coluna de água para as cadeias
tróficas.
O trabalho de campo foi realizado na Ria de Aveiro, em dois sítios específicos,
cuja caracterização em termos de contaminação por mercúrio já estava
descrita. Estudou-se a carga de mercúrio total na coluna de água, bem como o
mercúrio total e orgânico nos sedimentos e a sua transferência e acumulação
para peixes juvenis residentes na área, Liza aurata. O Cais do Bico, local mais
próximo da fonte de contaminação apresentou os maiores valores de mercúrio
total: 68 ng/L na coluna de água, 0,19 μg/g nos sedimentos e 0,07 μg/g nos
peixes. O local mais distante da fonte de mercúrio, Barra, apresentou uma
maior quantidade de mercúrio orgânico nos sedimentos (0,02 μg/g) e uma
percentagem de mercúrio orgânico no músculo dos peixes igualmente
superior, de 96%. Esta monitorização comprovou que, embora as descargas
industriais de mercúrio já tenham sido interrompidas no final do século
passado, o mercúrio armazenado nos sedimentos continua a ser
ressuspendido para a coluna de água, ficando biodisponível para a biota. A
utilização de organismos juvenis fornece informações sobre as variações a
curto prazo das concentrações de mercúrio no ambiente.
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VIANELLO, ELEONORA. "In vivo evaluation of biomolecular mechanisms of bilirubin toxicity and pre-clinical therapies." Doctoral thesis, Università degli Studi di Trieste, 2017. http://hdl.handle.net/11368/2908155.
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Introduction. Neonatal jaundice is a common and benign condition usually resolved during the first week of life. Neonates with very high level of unconjugated bilirubin (UCB), with an increase of the free bilirubin (Bf), may develop encephalopathy, with different grade of severity. Typical symptoms include motor disorder, auditory dysfunction, memory and learning deficits, reflecting selective damage respectively for cerebellum and basal ganglia, inferior colliculus, and hippocampus. Several studies reported that bilirubin may activate signal cascades that culminate to cell survival or death, as well as modulation of mRNA expression of genes involved in. Histone acetylation, an epigenetic mechanism responsible for the gene expression regulation via opening/closing of the chromatin, was never investigated in bilirubin-induced central nervous system (CNS) damage until now. The involvement of histone acetylation in common and rare neuropathologies was widely described, and also the potential neuroprotective action of drugs that regulate this epigenetic process.
Aims. By the use of the animal model for hyperbilirubinemia (Gunn rat), we purpose to investigate the modulation of the acetyl-histone H3 (lys14) (H3K14ac) in five brain regions (Cortex: Cx; Cerebellum: Cll; Superior Colliculi: SC; Inferior Colliculi: IC; Hippocampus: Hip) of hyperbilirubinemic animals (jj) vs. non hyperbilirubinemic littermates at four post natal ages (P2, P9, P17 and old). Moreover, we would like to individuate the genes regulated by H3K14ac in jj cerebella vs. controls at P9 and eventually interpret the biological effects of this epigenetic modulation performing histological stainings.
Results. Western blot analysis of H3K14ac level in all the brain regions and ages considered revealed a modulation of this protein that is region- and age-dependent. A significant increase of H3K14ac was observed in Cll, IC, and Hip in P9 jj animals, while a significant decrease was present in Cll and IC at P17 and Cx in older jj rats. ChIP-seq was performed in order to link the effect of hyperbilirubinemia on the H3K14ac with the genes controlled by this epigenetic mechanism in cerebella of P9 animals. Our data on H3K14ac in Cll and the fact that the cerebellar hypoplasia is the hallmark of hyperbilirubinemic Gunn rat supported this choice. Our results revealed that a very high number of genes regulated by H3K14ac was silenced in jj rats, while other few genes seemed to be activated in hyperbilirubinemic subjects. The gene ontology analysis showed that cellular development and differentiation, proliferation and migration, as well as apoptosis were the most modulated biological processes in jj rats. These ChIP-Seq data were confirmed by our histological findings, that revealed higher cell density with reduction of the fibrillary component and a possible impairment of cell differentiation.
Conclusions. This work reported for the first time the involvement of histone acetylation alterations in the brain of hyperbilirubinemic animals with a strong regulation of the gene expression. The complete panel of genes we obtained seemed to well-correlate with the bilirubin-induced damage that evidenced the development impairment. These data contribute to better understand the bio-molecular mechanisms that cause bilirubin toxicity but also might open to new therapeutical strategies in kernicterus, testing the neuroprotective properties of drugs that regulate the histone acetylation.
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Anand, Sridhar. "Structure-toxicity relationship studies of the sesquiterpene lactone repin /." Full text available from ProQuest UM Digital Dissertations, 2008. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1850447711&SrchMode=1&sid=5&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1279129305&clientId=22256.
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Thesis (Ph.D.)--University of Mississippi, 2008.<br>Typescript. Vita. "May 2008." Major professor: Dr. John M. Rimoldi Includes bibliographical references (leaves 121-143). Also available online via ProQuest to authorized users.
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Ziu, M. M. "Studies on the toxicity, distribution and metabolism of salicylate." Thesis, University of Liverpool, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356288.
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Navarro-Zornoza, Maria Dolores. "Improved predictive models for pre-clinical drug toxicity studies." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/21682.
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Increasingly, drug-induced liver injury is one of the main reason for drugs to be withdrawn from the market even after passing toxicity studies in pre-clinical and clinical trials because of risks of toxicity and ineffective treatments. Human immortalised hepatocyte cell lines used in drug testing are widely available, inexpensive and easy to culture. However, these cell lines are commonly known to have poor predictive capabilities and improved in vitro hepatic models are required for predicting hepatotoxicity of large numbers of compounds in drug discovery. In this study, the primary goal was to develop an improved in vitro human hepatic model using a combination of the C3A human hepatic cell line and human umbilical vein endothelial cells (HUVECs), for prediction of acetaminophen (APAP) hepatotoxicity. Initial experiments showed that co-culture of HUVEC:C3A in EGM-2, an endothelial medium, was essential to support both cell types, and that co-cultures maintained the initial cell seeding ratio of 1:1 (HUVEC:C3A) after 3 days. Phenotyping of co-cultured cells using platelet endothelial cell adhesion molecule (PECAM-1/CD31) for HUVECs, and hepatic epithelial (EpCAM) markers for C3As demonstrated that at ratio 1:1 (HUVEC:C3A), there is cross-talk between HUVECs and C3As and cells in co-culture showed properties of self-organisation. This interaction resulted in improved hepatic metabolic activity in vitro in respect of albumin synthesis and cytochrome P450 activity. Treatment with low (5 mM), intermediate (10 mM) and high doses (20 mM) of APAP, showed that prediction of hepatotoxicity using specific kits for cell viability and mitochondria function, was significantly improved in C3As in the presence of HUVECs, thus demonstrating an in vitro human hepatic co-culture could be an invaluable model for drug toxicity studies. We observed that the intermediate APAP dose had no effect on cell viability and mitochondrial function in co-cultures, whilst by comparison both lactate levels and oxidative stress were perturbed in mono-cultures. Co-cultures also up-regulated expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in HUVECs following APAP exposure, which may be important in modulating the toxic effect of APAP on C3As. To further improve the in vitro liver-like model, Matrigel™ was incorporated to promote vascular formation by HUVECs and support hepatic organization, migration and function of C3As. In HUVEC mono-cultures, Matrigel™-promoted vascularization, haptotaxis and self-organization and in HUVEC:C3A co-cultures formation of structures reminiscent of liver sinusoids and maintenance of hepatic albumin synthesis and CYP3A4 activity. Time-lapse imaging showed haptotactic migration of hepatocytes towards endothelial cells, with Matrigel™ likely having a chemotactic effect on HUVECs and C3As, resulting in interconnected vascular network. APAP inhibited angiogenesis in HUVEC mono-cultures whereas APAP had no effect in HUVEC:C3A co-cultures. In conclusion, the development of an in vitro human organotypic co-culture model of HUVECs and C3As significantly enhanced hepatic function, demonstrated by significant improvement in hepatic metabolism, evidence of greater resistance to APAP toxicity, and improved cell-cell communication. Co-cultures markedly modulated APAP hepatotoxicity compared with C3A mono-cultures. Furthermore, co-culture of HUVECs and C3As using a complex basement membrane biomatrix (Matrigel™) produced a self-assembling interconnected vascular network, improved hepatocyte function as well as reproducibility of responses to APAP toxicity. The application of the described co-culture models may improve the accuracy, efficacy and predictive power of drug toxicity testing strategies in drug development.
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Yu, Lok Chiu. "Cellular metabolism in in vitro toxicity and toxicology studies." HKBU Institutional Repository, 2005. http://repository.hkbu.edu.hk/etd_ra/675.
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Ganesan, Shobana. "Mechanistic studies of metabolism and toxicity of 8- aminoquinolines/." Full text available from ProQuest UM Digital Dissertations, 2009. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1798968881&SrchMode=1&sid=1&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1268338640&clientId=22256.
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Thesis (Ph.D.)--University of Mississippi, 2009.<br>Typescript. Vita. "May 2009." Major professor: Dr. Larry Walker Includes bibliographical references (leaves 154-168). Also available online via ProQuest to authorized users.
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Wright, Phillip. "An ex vivo model for the assessment of drug toxicity on the human retina." Thesis, University of East Anglia, 2016. https://ueaeprints.uea.ac.uk/59349/.
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Purpose: Retinal toxicity is a common cause of drug development attrition. The aims of this research were therefore to develop the ex vivo human retina as a suitable model for the assessment of retinotoxicity, and to explore the methods in which this may be investigated. Methods: Post mortem and living donor human eyes were obtained, and the retinas dissected within 24h post mortem or 1h enucleation respectively. The ex vivo human retina was characterised using immunohistochemistry and QRT-PCR. The effect of multiple retintoxins was investigated on the human retinal cell lines MIO-M1 (Müller cells) and ARPE19 (RPE cells), and CHQ on the human organotypic retinal culture (HORC) using the LDH and MTS assays. TUNEL, Western blotting and QRT-PCR were also used to investigate the effect of CHQ on the HORC, and CDK expression investigated by QRT-PCR. Results: Cell specific markers were investigated in the post mortem and living donor, both possessed similar immunohistochemical and mRNA properties. CHQ was the most potent retinotoxin investigated in the cell lines, and when applied to the HORC, measureable toxicity was found along with an increase in the expression of multiple cell specific mRNA’s. The expression profile of multiple CDK’s in the ex vivo retina was investigated in relation to a retinotoxic Pan-CDK inhibitor, where differential expression was found. When exposed to the retinotoxic pan-CDK inhibitor, the cell lines displayed differences in toxicity. Conclusion: The ex vivo human retina is an ideal tissue to investigate retinotoxicity. It possesses similar properties as the in vivo human retina, and displayed measureable toxicity when exposed to CHQ. The ex vivo human retina also proved its usefulness in the investigation genes associated to a novel retinotoxin. The ex vivo human retina could act as a bridge between animal and human studies, providing vital information about a drug’s potential retinotoxicity.
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Moyà, Anderico Laura. "Deciphering the utility of Galleria mellonella as an infection and toxicity in vivo model." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/671803.
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Galleria mellonella (greater wax moth) is a popular animal model that has been extensively used as an alternative in vivo model for investigating the virulence and pathogenicity of different bacteria. G. mellonella has also been shown to be a suitable model for studying the efficacy and toxicity of various compounds. Recently, this model has been gaining popularity as the larvae are conveniently sized for manipulation, they do not need constant feeding, they are inexpensive to purchase and to breed, they do not require much space or special infrastructure, they present a low biohazard risk, and they are more ethically accepted. More importantly, G. mellonella has an innate immune system very similar to the one found in mammals. In this thesis, G. mellonella was used to develop a standardized and reproducible animal model of infection and toxicity.
Pseudomonas aeruginosa is an opportunistic pathogen that has gained great medical importance as it causes serious illnesses in humans and it can be resistant to many antibiotics. During infection, ribonucleotide reductases (RNR) play an essential role as they catalyze the reduction of ribonucleotides to deoxyribonucleotides, thus providing the precursor molecules needed for DNA synthesis. Since G. mellonella has been proven to be a suitable model for P. aeruginosa infections, we developed a promoter probe vector with bioluminescence expression to enhance the study and monitoring of a P. aeruginosa in vivo infection. This vector was used to construct different RNR gene promoter fusions as proof of concept. Additionally, we optimized a total bacterial RNA extraction protocol to facilitate the study of transcriptional gene levels during in vivo infections.
Staphylococcus aureus is also considered an opportunistic pathogen. This bacterium is also capable of forming biofilms and it is considered an important cause of biofilm formation in catheters and prostheses. Due to the misuse and overuse of antimicrobials, multi-resistant bacteria are rapidly appearing so there is a critical need for new antimicrobials. The toxicity and antimicrobial efficacy against S. aureus of novel oleanolic and maslinic acid derivatives were determined using G. mellonella. Out of the 14 derivatives tested, 2 were found to have improved toxicity and efficacy in vivo when compared to the in vitro results.
G. mellonella was also used to test the toxicity of other therapeutical strategies and nanoparticles (NPs). Mycolicibacterium brumae was not toxic to G. mellonella larvae, and the results correlated with the results obtained with mice. The different NPs caused a variety of acute toxicity effects that were detected by an array of indicators within the larvae, such as lethal dose calculation, hemocyte proliferation, NP distribution, behavioral changes, and histological alterations. Due to the broad applicability of the G. mellonella model, new methodologies are warranted to exploit its full potential. Besides the optimized RNA extraction protocol already mentioned, an optical clearing protocol was also optimized in this work. As a proof of concept for our larvae clearance protocol, fluorescent rhodamine NPs were injected into larvae that were then fixed with paraformaldehyde, permeabilized with increasing concentrations of methanol, and cleared with BABB (Benzyl Alcohol and Benzyl Benzoate).<br>Galleria mellonella es un modelo animal utilizado extensamente como alternativa para investigar la virulencia y patogenicidad bacteriana in vivo. También es apropiado para estudiar la eficacia y toxicidad de compuestos. Las larvas tienen un tamaño manejable, son económicas de adquirir y reproducir, presentan un bajo riesgo biológico, y son más aceptadas
éticamente. Además, tienen un sistema inmunológico innato muy similar al de los mamíferos. Utilizamos G. mellonella para desarrollar un modelo animal de infección y toxicidad estandarizado y reproducible.
Pseudomonas aeruginosa, un patógeno oportunista, que infectando emplea ribonucleótido reductasa (RNR), catalizando la reducción de ribonucleótidos a desoxirribonucleótidos y proporcionando así las moléculas precursoras necesarias para la síntesis de ADN. Desarrollamos un vector sin promotor con bioluminiscencia, el cual se utilizó para construir fusiones con los promotores de los genes RNR. Además, optimizamos un protocolo de extracción de ARN bacteriano para facilitar el estudio de los niveles transcripcionales de genes in vivo.
Debido a la multiresistencia emergente de Staphylococcus aureus, se probó la toxicidad
y eficacia antimicrobiana de nuevos derivados del ácido oleanólico y maslínico en G. mellonella. De los catorce derivados probados, dos tenían menos toxicidad y más eficacia in vivo que in vitro.
G. mellonella se usó para determinar la toxicidad de nanopartículas y estrategias terapéuticas. Mycolicibacterium brumae no fue tóxica para las larvas y los resultados se correlacionaron con los obtenidos con ratones. Las nanopartículas causaron efectos tóxicos en las larvas detectados por la medición de la dosis letal y la proliferación de hemocitos, entre otros indicadores.
Debido a la amplia aplicabilidad de G. mellonella, se necesitan nuevas metodologías para maximizar su potencial. Además del protocolo de extracción de ARN previamente mencionado, también se optimizó otro de aclaramiento. Las larvas fueron inyectadas con nanopartículas, fijadas con paraformaldehído, permeabilizadas con metanol y aclaradas con alcohol bencílico y benzoato de bencilo.
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Pan-Bartneck, Yu [Verfasser]. "Assessing the toxicity of gold nanoparticles in vitro and in vivo / Yu Pan-Bartneck." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2011. http://d-nb.info/1018226168/34.
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Al-Duaij, Ahmed Yousuf Mohamed. "Studies of cartilage degradation in vivo." Thesis, Queen Mary, University of London, 1985. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1366.
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A new method has been established to study cartilage breakdown in vivo. Cartilage was implanted into air pouches on the backs of mice or rats and loss of proteoglycan measured biochemically. Using the air pouch it was possible to produce various inflammatory environments either immune or non immune and examine the effects of these upon proteoglycan loss. It was found that the various type of inflammation failed to accelerate proteoglycan loss from implanted cartilage. Subsequently a variety of drugs used in the treatment of the arthropathies were examined for their effect on both inflammation and cartilage breakdown. Using xiphisternum a difference could be shown between non-steroidal anti-inflammatory drugs (NSAID) and d-penicillamine in that, NSAID failed to protect the cartilage whereas d-penicillamine prevented proteoglycan loss. This type of cartilage was not examined further, as it was not characteristic of articular cartilage - being surrounded by perichondrium. Later articular cartilage was implanted once again into different inflammatory situations and drug effects evaluated. It was found using this cartilage that all the drug 0 used protected from loss of proteoglycan and whereas some inhibited inflammation (indoniethacin and dexamethasohe), 2a levamisole had no effect in contrast, d-penicillamine potentiated the inflammatory response. Finally the mode of action of the drugs in this method is discussed.
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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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Higgins, C. "Gossypol toxicity and anti-fertility action : Studies of possible mechanisms." Thesis, University of Manchester, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356105.
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Lawrence, J. N. "Cryopreservation and toxicity studies with cultured rat and human hepatocytes." Thesis, University of Surrey, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233123.
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Zhang, Chang. "Mammalian prion toxicity studies in cytoplasmic ovine PrP transgenic Drosophila." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648399.
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Dinesan, K. C. "Histopathological studies on zinc toxicity in Milkfish Chanos chanos Forsskal." Thesis, Central Marine Fisheries Research Institute, 1988. http://eprints.cmfri.org.in/11054/1/Dinesan%20K.C..pdf.
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Aquaculture embraces a wide range of activities from ’Searanching'
and management of activities in large bodies of water to intensive
culture with fertilization and feeding of fish in small manmade
ponds. It is an age old practise in different parts of the world and recently its potential in upgrading rural economy in developing countries has been recognized by International Organizations like FAO.
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Masango, Mxolisi Goodwill. "A comparative analysis of the cytotoxicity of cyanotoxins using in vitro (cell culture) and in vivo (mouse) assays." Diss., Pretoria : [s.n.], 2007. http://upetd.up.ac.za/thesis/available/etd-05122008-100402/.
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Agha, Samiullah K. "Studies on the integration of growth in stoloniferous clonal herbs." Thesis, Bangor University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267325.
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Kim, Jong Sung. "Evaluating pulmonary toxicity of engineered metal-based nanoparticles using in vivo and in vitro models." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/2726.
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The overall goals of this doctoral dissertation were to 1) assess effects of nanoparticle (NP) exposure on host defense in a murine pulmonary infection model, 2) evaluate an integrated dynamic in vitro exposure system (DIVES) that overcomes limitations of submerged exposure systems for NP toxicity testing and 3) provide information on the rank of NP toxicity and assess the potential of the DIVES as a screening tool for NP toxicity. To achieve the first goal, we used Klebsiella pneumoniae (K.p.) in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by copper (Cu) NP exposure. Cu NP exposure induced strong inflammatory responses and an impairment in host defense against bacterial lung infections in both inhalation and instillation exposure studies even though there was an upregulation of pro-inflammatory cytokines and recruitment of neutrophils to the lungs. Thus, Cu NP exposure may lead to increased risk of pulmonary infection by impairing host defense against bacteria. In the second study, we integrated the DIVES capable of generating NP aerosols and depositing NPs directly onto cells grown at the air-liquid interface (ALI) to mimic a more realistic in vivo pulmonary exposure to inhaled NPs. Furthermore, we characterized the efficiency of NP delivery, the distribution of particle deposition and the effects of exposure conditions in the DIVES on the viability of A549 cells (human alveolar type-II-like cancer cells) as a precursor to studies of NP toxicity. The DIVES was shown to provide efficient, uniform and controlled dosing of particles to epithelial cells grown at the ALI. In addition, this exposure system delivered a continuous airborne-exposure of NPs to lung cells without loss of cellular viability. Lastly, to assess the DIVES as a means to rank NP toxicity and prioritize NPs for in vivo testing, we compared in vitro measurements obtained using the DIVES and the submerged exposure system to in vivo results obtained using a murine model of lung inflammation. Exposure to Cu NPs induced a significant increase in cytotoxicity and inflammatory responses compared to Fe NPs at the ALI in the DIVES. The results of this comparison suggest that air-delivery of NPs to lung cells using the DIVES can provide evidence of toxicity at a lower concentration of NPs compared to responses in the submerged condition. More importantly, our in vitro results presented in this dissertation are in agreement with our in vivo findings showing that Cu NPs have a higher propensity for NP dissolution and this may contribute to the greater toxicity of Cu NPs than Fe NPs. Thus, the results of these comparisons suggest that the DIVES has a significant potential for screening NP toxicity and allows for a higher throughput than in vivo studies. Overall, we found that exposure of lung cells at the ALI using the DIVES is preferable to submerged exposure for in vitro NP toxicity testing and provides useful information on the rank of NP toxicity and prioritization of NPs for in vivo testing.
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Meade, Angela. "Studies on the mechanisms of pancreatic B cell dysfunction in diabetes." Thesis, University of Ulster, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268558.
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Rawlings, Sally Jeanette. "Studies on the teratogenicity of methoxyacetic acid." Thesis, University of Surrey, 1987. http://epubs.surrey.ac.uk/847930/.
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The teratogenicity of methoxyacetic acid (MAA) was studied using rat whole-embryo and limb bud micromass cultures. MAA and some related alkoxy acids were direct-acting teratogens in both systems. Structure-activity investigations produced the same rank-order of potency; methylthioacetate > MAA > ethoxyacetate. All other compounds tested were either much less effective or inactive. In whole embryo culture the uptake of MAA was rapid, appeared to be by simple diffusion, and to be determined by pH partitioning. MAA accumulated in the relatively alkaline conceptus; for example, the exocoelomic fluid concentration was 1.7 fold that of the medium. In micromass cultures uptake was also dependent on pH partitioning, hence MAA was more effective in Hams F-12 (pH 7.1) medium than in DMEM (pH 7.6). MAA did not appear to be metabolised by the rat embryo in culture. After a 48 h exposure, radiolabel derived from MAA was not incorporated into macromolecular fractions (lipid, RNA, DNA, or protein) of the developing conceptus. Also, HPLC analysis of the acid-soluble phase of embryonic tissue and media samples did not reveal methoxyacetylglycine or any other known MAA metabolite. Using both culture systems it was shown that MAA did not evoke its teratogenic response via an initial inhibitory effect on either DNA or protein synthesis, glycolysis, nor the incorporation of acetate or sulphate. In addition, MAA did not inhibit yolk-sac pinocytosis. The first day of a 6 day micromass culture was most sensitive to MAA treatment. The protein content and cell number of treated cultures were severely reduced by 24 h, indicating cell death and/or cell loss. Thus, biochemical measurements taken at 24 h or later may reflect secondary, rather than initial, insults. Replating of MAA-treated micromass cultures (after a 24 h exposure), to re-establish normal cell density, did not restore the ability to form chondrogenic foci. The inhibition of differentiation was not, therefore, freely reversible nor the result of a decreased cell density, but may be due to selective cytotoxicity against the sub-population of pre-chondrogenic cells.
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De, Varennes Benoit. "Ex-vivo canine heart preservation : metabolic studies." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56680.
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The recently developed method of nuclear magnetic resonance spectroscopy allows for continuous monitoring of high energy phosphate compound (ATP and Phosphocreatine) and intracellular pH of tissues or whole organs. In other to better understand why ex-vivo hearts can be preserved for longer periods when perfused with oxygenated crystalloid solutions under hypothermic conditions, two groups of canine hearts were studied with nuclear magnetic resonance spectroscopy.<br>Group 1 = Canine hearts preserved for 4 hours by immersion into a 4$ sp circ$C saline solution.<br>Group 2 = Canine hearts preserved for 24 hours by continuous coronary perfusion with a modified oxygenated Krebs solution at 4$ sp circ$C.<br>The longer preservation of ATP and phosphocreatine, as well as the slower decrease of intracellular pH in Group II hearts are hypothesized to be the reasons why perfused hearts can be preserved for longer periods of time.
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Haggie, P. M. "Spectroscopic studies of labelled proteins in vivo." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599831.
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Although metabolic enzymes and metabolic pathways have been well characterised <I>in vitro, </I>understanding of the control of metabolic processes <I>in vivo </I>is relatively poor. The extrapolation of studies performed on purified proteins into the intact cell is questionable. Consequently, there is a need to study enzymes <I>in vivo</I>, however, there are a limited number of techniques available to study specific proteins in a minimally invasive manner. Reported in this thesis are studies in which techniques are developed to permit specific proteins to be distinguished using nuclear magnetic resonance (NMR) and fluorescence visibility. A method to selectively label proteins by the biosynthetic incorporation of amino acid analogs has been developed in <I>Saccharomyces cerevisiae. </I>This method is non-invasive, and the probes introduced into specific proteins are very small and relatively non-perturbing. Using an inducible expression system, pyruvate kinase 1 and citrate synthase 1 were synthesised <I>in vivo</I> and 5-fluorotryptophan in the growth medium was selectively incorporated into the proteins. This labelling permitted the visualisation of these proteins using non-invasive NMR of whole cells. A complementary optical technique was also developed. This method incorporated a fluorescent amino acid analog (5-hydroxytryptophan) into proteins to allow the study of the proteins using more sensitive fluorescence techniques in whole cells. 5-Hydroxytryptophan was successfully incorporated into phosphoglycerate kinase which permitted visualisation of the protein in whole cells using laser scanning confocal microscopy. For both pyruvate kinase 1 and citrate synthase 1, there was evidence of enzyme immobilisation in whole cells. These investigations present direct evidence for the association of enzymes <I>in vivo</I>. The implications of these results in terms of the organisation of metabolism are discussed. The fluorescence studies have important implications both in terms of studying proteins <I>in vivo</I> with microscopy and fluorimetry and in the development of techniques to fluorescently label proteins.
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Frost, Gwenda. "In vivo NMR studies of Debaryomyces hansenii." Thesis, University of Liverpool, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316609.
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Preece, N. E. "Studies on chemical-induced autoxidation in vivo." Thesis, University of Surrey, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376361.
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Marczinke, Beate Inge. "In vivo studies of viral ribosomal frameshifting." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624918.
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