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Biological Effects of Low Dose Radiation from Computerized Tomography ScansAsis, Angelica 01 1900 (has links)
Humans have evolved under a field of low level radiation, and continue to be exposed
to ubiquitous levels from natural and man-made sources including diagnostic radiology. The
computerized tomography scan, in particular, plays an important role in the investigation of
disease and its use increased dramatically over the years. This raises the concern that
elevation in radiation exposure from x-ray modalities may increase an individual's risk for
cancer. The purpose of this study is to help address this issue by measuring biological
changes in lymphocytes before and after a CT scan. Venous blood was collected from eight
prostate cancer patient:> before and after their scan and delivered to McMaster University at
room temperature. For the dicentric assay, 0.5 ml whole blood/tube was irradiated with 3 Gy
gamma rays using a 0 ;137 source and then incubated at 37°C for 46 hours. Metaphases were
scored by microscopy. For apoptosis and y-H2AX, lymphocytes in media were irradiated on
ice with 8 Gy and analyzed by flow cytometry. Biological effects in vivo from the CT scan
were minimal for all endpoints when averaged between all donors. Overall, there was a high
degree of inter-individual variation for each effect, although no correlation was found
between dose (dose length product) from CT and apoptosis as well as the induction of yH2AX
foci. The adaptive response also showed patient variation, and the frequency of
dicentrics was the only endpoint that was lower overall following CT + 3Gy in comparison to
3 Gy alone. This research presents a challenge to current linear models of radiation
associated genetic risk, and shows that individuals respond to radiation differently depending
on biological factors. / Thesis / Master of Science (MSc)
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New methods to overcome radioresistanceShort, Susan Christine January 2000 (has links)
No description available.
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OPIOIDS AND GLIA: INVESTIGATING THE MECHANISMS THROUGH WHICH ULTRA-LOW DOSE OPIOID ANTAGONISTS MODULATE OPIOID TOLERANCE AND HYPERALGESIA.Mattioli, THERESA ALEXANDRA 25 April 2013 (has links)
Ultra-low doses (ULD) of the opioid receptor antagonists, naloxone and naltrexone, augment the analgesic actions of morphine, block the induction of tolerance, and reverse established tolerance by an unknown mechanism. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Thus, this thesis investigated the inhibition of spinal gliosis as a mechanism by which ULD antagonists attenuate analgesic tolerance and opioid-induced hyperalgesia.
Immune cell activation is implicated in the etiology of morphine tolerance and intrathecal catheterization, a technique commonly used to study the spinal effects of drugs, causes profound gliosis. Thus, the first study investigated the effects of catheter-induced gliosis on acute and chronic morphine analgesic tolerance. Catheterization-induced gliosis did not alter antinociceptive responses to acute intrathecal morphine; however, tolerance to chronic morphine was exacerbated in catheterized rats compared to sham and surgery-naïve controls.
The potentiation of analgesic tolerance to chronic morphine by spinal gliosis provided evidence that glia modulate opioid analgesia; therefore, inhibition of opioid-induced activation of glia was explored as a potential mechanism by which ULD antagonists prevent tolerance. The second series of experiments reported morphine-induced activation of spinal microglia and astrocytes was blocked by co-administering ULD naltrexone with morphine. These findings prompted us to elucidate the specific molecular target through which ULD antagonists attenuate opioid analgesia.
Activation of glial Toll-like receptor 4 (TLR4) induces gliosis and may contribute to analgesic tolerance and/or morphine-induced hyperalgesia (MIH). Antagonism of TLR4 by the opioid receptor-inactive (+) stereoisomer of naloxone was identified as a potential mechanism by which ULD antagonists modulate opioid analgesia. Tolerance and MIH developed in mice expressing non-functional TLR4 and in wildtype controls. Analgesic tolerance was stereoselectively blocked by ULD (-)naloxone, whereas MIH was blocked by both naloxone enantiomers.
Collectively, these studies demonstrate analgesic tolerance and MIH occur through distinct mechanisms. ULD naloxone attenuates analgesic tolerance likely via an opioid receptor-mediated mechanism that is TLR4-independent. ULD antagonists do not attenuate tolerance via inhibition of spinal gliosis as hypothesized. In contrast, ULD antagonists prevent MIH by inhibiting opioid-induced gliosis in an opioid receptor- and TLR4-independent manner.
Immune cell activation is implicated in the etiology of morphine tolerance and intrathecal catheterization, a technique commonly used to study the spinal effects of drugs, causes profound gliosis. Thus, the first study investigated the effects of catheter-induced gliosis on acute and chronic morphine analgesic tolerance. Catheterization-induced gliosis did not alter antinociceptive responses to acute intrathecal morphine; however, tolerance to chronic morphine was exacerbated in catheterized rats compared to sham and surgery-naïve controls.
The potentiation of analgesic tolerance to chronic morphine by spinal gliosis provided evidence that glia modulate opioid analgesia; therefore, inhibition of opioid-induced activation of glia was explored as a potential mechanism by which ULD antagonists prevent tolerance. The second series of experiments reported morphine-induced activation of spinal microglia and astrocytes was blocked by co-administering ULD naltrexone with morphine. These findings prompted us to elucidate the specific molecular target through which ULD antagonists attenuate opioid analgesia.
Activation of glial Toll-like receptor 4 (TLR4) induces gliosis and may contribute to analgesic tolerance and/or morphine-induced hyperalgesia (MIH). Antagonism of TLR4 by the opioid receptor-inactive (+) stereoisomer of naloxone was identified as a potential mechanism by which ULD antagonists modulate opioid analgesia. Tolerance and MIH developed in mice expressing non-functional TLR4 and in wildtype controls. Analgesic tolerance was stereoselectively blocked by ULD (-)naloxone, whereas MIH was blocked by both naloxone enantiomers.
Collectively, these studies demonstrate analgesic tolerance and MIH occur through distinct mechanisms. ULD naloxone attenuates analgesic tolerance likely via an opioid receptor-mediated mechanism that is TLR4-independent. ULD antagonists do not attenuate tolerance via inhibition of spinal gliosis as hypothesized. In contrast, ULD antagonists prevent MIH by inhibiting opioid-induced gliosis in an opioid receptor- and TLR4-independent manner. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2013-04-25 15:06:50.731
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Role of MTH1 and MYH proteins in genotoxic effects of radiationShakeri Manesh, Sara January 2015 (has links)
Humans are constantly exposed to different types of radiations. It has been suggested that low dose and low dose rate of γ-radiation as well as ultra violet A (UVA) induce oxidative stress in cells that may promote mutations. The mechanisms behind radiation-induced oxidative stress and its relation to genotoxicity and cancer induction are not well understood. In the majority of investigations, the DNA molecule has been studied as the target for mutations, however the results obtained in our group point out that DNA bases in the cytoplasm could also be a significant target. MTH1 and MYH are two of the key proteins of the repair pathway that prevent mutations arising from oxidized DNA bases. In this thesis, we studied the role of MTH1 and MYH in genotoxicity of UVA and γ-radiation. The adaptive response to low dose rates of γ-radiation was also investigated. MTH1 and/or MYH were knockdown in human lymphoblastoid TK6 cells. The clonogenic survival, mutant frequency and chromosomal aberration assays were performed following UVA or γ-radiation exposure. Our results indicated that acute exposure to UVA or γ-radiation affects cell survival and also increases the mutant frequency above the background. The mutant frequency in MTH1 deficient cells was higher than that in wild types after UVA exposure. Following γ-radiation exposure, a higher mutant frequency was observed in the MYH and MTH1 deficient cells, in comparison to either MYH or MTH1 deficient or wild type cells. No dose rate effect of γ-radiation for mutations was observed. An adaptive response to γ-radiation was observed at the mutation level in MCF-10A cells but not at the survival level. In summary, our results suggest that; a) MYH and MTH1 cooperatively protect cells against genotoxic effects of γ-radiation; b) MTH1 protects cells from UVA-induced mutations; c) low dose rates of γ-radiation may induce an adaptive response at the mutation level; d) there is no dose rate effect for γ-radiation at the mutation level. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.</p>
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Effets de mélanges de pesticides sur les biofilms périphytiques d'eau douceKim Tiam, Sandra 05 December 2013 (has links)
On considère généralement les biofilms comme des indicateurs biologiques d’alerte, les organismes les composant ayant des temps de génération relativement courts et présentant une grande diversité de preferenda environnementaux et de sensibilité aux altérations anthropiques. Dans ces travaux, les effets de pesticides sur les biofilms de rivière ont été étudiés à différentes échelles de représentativité, allant de mélanges complexes à faible dose en utilisant des extraits d’échantillonneur passif POCIS (Polar Organic Chemical Integrative Sampler) à des molécules testées seules, en passant par des mélanges simples.L’exposition chronique et à faible dose aux extraits de POCIS a révélé des impacts au niveau de la croissance, de la structure (assemblages de diatomées) et du fonctionnement du biofilm en lien avec son exposition passée. De plus les expériences utilisant des molécules testées seules (pesticides et métabolites) et les mélanges simples ont permis de caractériser la toxicité relative des composés présents dans les extraits de POCIS en lien avec leur mode d’action et d’explorer la réponse de descripteurs encore peu utilisés en écotoxicologie comme la construction de Rapid Light Curves (RLCs).Ce travail confirme la pertinence de l’utilisation des extraits d’échantillonneurs passifs comme le POCIS pour mieux appréhender les effets des pesticides en mélanges sur le biofilm de rivière ainsi que l’intérêt des RLCs en tant que descripteur précoces d’exposition aux pesticides. / Biofilms can be regarded as biological warming systems, because they are generally composed of short generation time organisms presenting a large range of environmental preferenda and various sensibilities to anthropogenic disturbance. In the present study, effects of pesticides on river biofilms have been studied at different levels of representativeness, from complex mixtures at low dose represented by POCIS passive sampler extracts (Polar Organic Chemical Integrative Sampler) to molecules tested alone via simple mixtures.Chronic exposure to low dose of POCIS extracts revealed impacts on growth related, structural (diatom assemblages) and functional parameters related to biofilm exposure history. Moreover experiment using single molecules and simple mixtures allowed to characterised the relative toxicity of compounds present in the POCIS extracts in link with their specific mode of action and explore the response of descriptor not very used in ecotoxicology field like the construction of Rapid Light Curves (RLCs).This work confirms the relevance of the use of passive sampler extracts as POCIS in order to better understand the effects of pesticides in mixture on river biofilms as well as the interest of RLCs as early exposure descriptors of pesticides exposure.
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Assessment of Low-Dose Radiotoxicity in Microorganisms and Higher OrganismsObeid, Muhammad Hassan 18 January 2016 (has links) (PDF)
This work was dedicated to quantify and distinguish the radio- and chemitoxic effects of environmentally relevant low doses of uranium on the metabolism of microorganisms and multicellular organisms by a modern and highly sensitive microcalorimetry. In such low-dose regime, lethality is low or absent. Therefore, quantitative assays based on survival curves cannot be employed, particularly for multicellular organisms. Even in the case of microbial growth, where individual cells may be killed by particle radiation, classical toxicity assessments based on colony counting are not only extremely time-consuming but also highly error-prone.
Therefore, measuring the metabolic activity of the organism under such kinds of conditions would give an extremely valuable quantitative measure of viability that is based on life cell monitoring, rather than determining lethality at higher doses and extrapolating it to the low dose regime. The basic concept is simple as it relies on the metabolic heat produced by an organism during development, growth or replication as an inevitable byproduct of all biochemical processes. A metabolic effect in this concept is defined as a change in heat production over time in the presence of a stressor, such as a heavy metal. This approach appeared to be particular versatile for the low dose regime. Thus, the thesis attempted in this case to measure the enthalpy production of a bacterial population as a whole to derive novel toxicity concepts.
In the following chapters, an introduction about the properties of ionizing radiation will be briefly presented, in addition to a review about the isothermal calorimetry and its application in studying the bacterial growth. Later in chapter 2, the effect of uranium on the metabolic activity of three different bacterial strains isolated form a uranium mining waste pile together with a reference strain that is genetically related to them will be investigated. Due to the lack of published dedicated calibration techniques for the interpretation of heat production of bacterial cells under the conditions of calorimetric recordings, additional experiments, thorough investigations of the effects of experimental conditions, have been carried out in order to guide the interpretation of calorimetric results.
In chapter 3, the differentiation between chemi- and radiotoxicity of uranium has been addressed by isotope exchange, which was a key effort in this thesis as it opens new experimental approaches in radioecology. In chapter 4, through investigating the role of the tripeptide glutathione (GSH) in detoxifying uranium, it will be shown to which degree the intrinsically unspecific signal provided by metabolic heat can be related to highly specific metabolic pathways of an organism, when combined with genetic engineering. The demonstration of gaining molecule-specific information by life metabolic monitoring was another experimental challenge of this thesis and provides proof of principle that can be extended to many organisms.
Finally in chapter 5, an attempt has been undertaken to establish a minimal food chain, in order to study the effects of the exposure of a multicellular organism to uranium through its diet.
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Desenvolvimento de uma camara de extrapolacao como instrumento de referencia para dosimetria de radiacao betaDIAS, SIMONE K. 09 October 2014 (has links)
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Differenzierung der Pharmakotherapie mit Fasudil und Riluzol im SOD1-G93A Mausmodell der Amyotrophen Lateralsklerose / Differentiation of pharmacotherapy with Fasudil and Riluzole in the SOD1G93A mouse model of amyotrophic lateral sclerosisScheer, David 05 December 2018 (has links)
No description available.
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Efeitos de baixas doses de radiacao do Co-60 (radio-hormesis) em sementes de tomate / Effect of low doses of gamma radiation of Co-60 (Radio-hormesis) in tomato seedsWIENDL, TONI A. 09 October 2014 (has links)
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Desenvolvimento de uma camara de extrapolacao como instrumento de referencia para dosimetria de radiacao betaDIAS, SIMONE K. 09 October 2014 (has links)
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